umu.sePublications
Change search
Refine search result
2324252627 1251 - 1300 of 1315
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1251.
    Wirell, Staffan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Binding of radiographic contrast media to serum proteins: a clinical and experimental investigation of their adverse effects through influence on active steroid hormone levels1982Doctoral thesis, comprehensive summary (Other academic)
  • 1252.
    Wu, Cuiyan
    et al.
    School of Public Health, Health Science Center of Xi'an Jiaotong University; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the People's Republic of China, Xi'an, P.R. China.
    Liu, Huan
    School of Public Health, Health Science Center of Xi'an Jiaotong University; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the People's Republic of China, Xi'an, P.R. China.
    Zhang, Feng'e
    School of Public Health, Health Science Center of Xi'an Jiaotong University; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the People's Republic of China, Xi'an, P.R. China.
    Shao, Wanzhen
    School of Public Health, Health Science Center of Xi'an Jiaotong University; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the People's Republic of China, Xi'an, P.R. China.
    Yang, Lei
    School of Public Health, Health Science Center of Xi'an Jiaotong University; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the People's Republic of China, Xi'an, P.R. China.
    Ning, Yujie
    School of Public Health, Health Science Center of Xi'an Jiaotong University; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the People's Republic of China, Xi'an, P.R. China.
    Wang, Sen
    School of Public Health, Health Science Center of Xi'an Jiaotong University; Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the People's Republic of China, Xi'an, P.R. China.
    Zhao, Guanghui
    Department of Knee Joint, Xi'an Hong Hui Hospital, Xi'an, P.R. China.
    Lee, Byeong Jae
    Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, Korea.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Guo, Xiong
    Long noncoding RNA expression profile reveals lncRNAs signature associated with extracellular matrix degradation in kashin-beck disease2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 17553Article in journal (Refereed)
    Abstract [en]

    Kashin-Beck disease (KBD) is a deformative, endemic osteochondropathy involving degeneration and necrosis of growth plates and articular cartilage. The pathogenesis of KBD is related to gene expression and regulation mechanisms, but long noncoding RNAs (lncRNAs) in KBD have not been investigated. In this study, we identified 316 up-regulated and 631 down-regulated lncRNAs (≥ 2-fold change) in KBD chondrocytes using microarray analysis, of which more than three-quarters were intergenic lncRNAs and antisense lncRNAs. We also identified 232 up-regulated and 427 down-regulated mRNAs (≥ 2-fold change). A lncRNA-mRNA correlation analysis combined 343 lncRNAs and 292 mRNAs to form 509 coding-noncoding gene co-expression networks (CNC networks). Eleven lncRNAs were predicted to have cis-regulated target genes, including NAV2 (neuron navigator 2), TOX (thymocyte selection-associated high mobility group box), LAMA4 (laminin, alpha 4), and DEPTOR (DEP domain containing mTOR-interacting protein). The differentially expressed mRNAs in KBD significantly contribute to biological events associated with the extracellular matrix. Meanwhile, 34 mRNAs and 55 co-expressed lncRNAs constituted a network that influences the extracellular matrix. In the network, FBLN1 and LAMA 4 were the core genes with the highest significance. These novel findings indicate that lncRNAs may play a role in extracellular matrix destruction in KBD.

  • 1253.
    Wu, Xiaofang
    et al.
    College of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, PR China.
    Han, Jing
    College of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, PR China.
    Yi, Jianhua
    College of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, PR China.
    Wang, Zuyong
    Biomat lab, Department of Mechanical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Li, Danyang
    College of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, PR China.
    Yu, Fangfang
    College of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, PR China.
    Guo, Xiong
    College of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, PR China.
    The effects of chondroitin and/or glucosamine on patients with Kashin-Beck disease2016In: Science Insights Medicine, ISSN 2378-8097, Vol. 2016, article id e00019Article, review/survey (Refereed)
    Abstract [en]

    Kashin-Beck disease (KBD), an endemic disease, is a special type of osteoarthritis (OA). Nowadays, due to prevention and treatment methods including selenium supplements, changing grains and water source as well as health education, the morbidity of KBD is reduced significantly as compared to that in the 1950s. However, many elderly adult KBD patients are still suffering from the degenerative changes of cartilage, pain, stiffness and deformation of joints, which are quite similar or even more serious than OA. Chondroitin sulfate and glucosamine have been widely used as symptomatic slow-acting drugs for the treatment of OA. Although their therapeutic effects, biochemical data, pharmacokinetics, preclinical studies, safety and economic evaluation have been well investigated in OA, they are not clearly studied in KBD. In this review, we will evaluate the clinical evidence (randomized controlled trials and non-randomized controlled trials), safeties and cost-effectiveness of chondroitin sulfate and glucosamine for the treatment of KBD. Moreover, the therapeutic mechanisms of chondroitin sulfate and glucosamine are also discussed in details.

  • 1254.
    Wählby, Lennart
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Achilles tendon injury: aspects on muscle structure and strength1978Doctoral thesis, comprehensive summary (Other academic)
  • 1255.
    Wåhlin, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Fordell, Helena
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Ekman, Urban
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Lenfeldt, Niklas
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Rehabilitation in chronic spatial neglect strengthens resting-state connectivity2019In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 139, no 3, p. 254-259Article in journal (Refereed)
    Abstract [en]

    Objectives: Rehabilitation of patients with chronic visuospatial neglect is underexplored, and little is known about neural mechanisms that can be exploited to promote recovery. In this study, we present data on resting-state functional connectivity within the dorsal attention network (DAN) in chronic neglect patients as they underwent training in a virtual reality (VR) environment that improved left-side awareness.

    Methods: The study included 13 patients with visuospatial neglect persisting more than six months after a right-sided stroke. The patients underwent resting-state functional magnetic resonance imaging (fMRI). Scans were collected at baseline and after five weeks of intense training. We specifically examined resting-state functional connectivity within the DAN. In addition, using spatial concordance correlation, we compared changes in the spatial topology of the DAN with that of other networks.

    Results: We found a longitudinal increase in interhemispheric functional connectivity between the right frontal eye field and the left intraparietal sulcus following training (before: 0.33 +/- 0.17 [mean +/- SD]; after: 0.45 +/- 0.13; P = 0.004). The spatial concordance analyses indicated that training influenced the DAN connectivity more than any of the other networks.

    Conclusion: Intense VR training that improved left-sided awareness in chronic stroke patients also increased sporadic interhemispheric functional connectivity within the DAN. Specifically, a region responsible for saccadic eye movement to the left became more integrated with the left posterior parietal cortex. These results highlight a mechanism that should be exploited in the training of patients with chronic visuospatial neglect.

  • 1256.
    Wåhlin, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    At the Heart of Cognitive Functioning in Aging2019In: Trends in cognitive sciences, ISSN 1364-6613, E-ISSN 1879-307X, Vol. 23, no 9, p. 717-720Article in journal (Other academic)
    Abstract [en]

    Several neural and non-neural factors contribute to individual differences in cognitive performance. Here we outline a sequence of vascular events where excessive transfer of arterial-pressure pulsatility damages hippocampal capillaries. We argue that the vascular alterations decrease the ability to sustain neural activity and thereby contribute to episodic-memory impairment in aging.

  • 1257. Yanagita, Tadahiko
    et al.
    Murata, Yoji
    Tanaka, Daisuke
    Motegi, Sei-ichiro
    Arai, Eri
    Daniwijaya, Edwin Widyanto
    Hazama, Daisuke
    Washio, Ken
    Saito, Yasuyuki
    Kotani, Takenori
    Ohnishi, Hiroshi
    Oldenborg, Per-Arne
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Garcia, Noel Verjan
    Miyasaka, Masayuki
    Ishikawa, Osamu
    Kanai, Yae
    Komori, Takahide
    Matozaki, Takashi
    Anti-SIRP alpha antibodies as a potential new tool for cancer immunotherapy2017In: JCI Insight, ISSN 2379-3708, Vol. 2, no 1, article id e89140Article in journal (Refereed)
    Abstract [en]

    Tumor cells are thought to evade immune surveillance through interaction with immune cells. Much recent attention has focused on the modification of immune responses as a basis for new cancer treatments. SIRP alpha is an Ig superfamily protein that inhibits phagocytosis in macrophages upon interaction with its ligand CD47 expressed on the surface of target cells. Here, we show that SIRP alpha is highly expressed in human renal cell carcinoma and melanoma. Furthermore, an anti-SIRP alpha Ab that blocks the interaction with CD47 markedly suppressed tumor formation by renal cell carcinoma or melanoma cells in immunocompetent syngeneic mice. This inhibitory effect of the Ab appeared to be mediated by dual mechanisms: direct induction of Ab-dependent cellular phagocytosis of tumor cells by macrophages and blockade of CD47-SIRP alpha signaling that negatively regulates such phagocytosis. The antitumor effect of the Ab was greatly attenuated by selective depletion not only of macrophages but also of NK cells or CD8(+) T cells. In addition, the anti-SIRP alpha Ab also enhances the inhibitory effects of Abs against CD20 and programmed cell death 1 (PD-1) on tumor formation in mice injected with SIRP alpha-nonexpressing tumor cells. Anti-SIRP alpha Abs thus warrant further study as a potential new therapy for a broad range of cancers.

  • 1258. Yang, Lei
    et al.
    Liu, Huan
    Guo, Xiong
    Lammi, Mikko Juhani
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Xi'an, People's Republic of China.
    The potential biochemical markers of Kashin-Beck disease: a meta-analysis2016In: Biomarkers, ISSN 1354-750X, E-ISSN 1366-5804, Vol. 21, no 7, p. 633-638Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The objective of this study is to explore the cytokines in serum, synovial fluid as potential biomarkers of Kashin-Beck disease (KBD) and to further understand the role of these cytokines in the pathogenesis of KBD.

    METHODS: A systematic electronic database search was performed from inception up to 15 March 2015. Meta-analysis was performed for cytokines more than one repetition in studies with available data. The effect size was summarized as standardized mean difference (SMD) with 95% confidence intervals (CIs) by a random effect model.

    RESULTS: A total of 18 articles were included. The pooled standardized mean differences showed the serum levels of tumor necrosis factor alpha (2.72, 95% CI: 1.8 5-3.59), interleukin-1 beta (1.21, 95% CI: 0.6 1-1.80), and nitric oxide (2.60, 95% CI: 1.5 2-3.68) were significantly higher in adult KBD patients compared with that in healthy controls.

    CONCLUSIONS: There was explicit evidence showing that the tumor necrosis factor alpha, interleukin-1 beta and nitric oxide were closely related to the presence of KBD, and these cytokines played a vital role in the pathogenesis of KBD.

  • 1259.
    Yang, Lei
    et al.
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Xi'an, PR China.
    Zhang, Jianping
    School of Clinical Medicine, Hainan Medical University, Haikou, PR China.
    Zhao, Guanghui
    Hong Hui Hospital, Health Science Center, Xi'an Jiaotong University, Xi'an, PR China.
    Wu, Cuiyan
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Xi'an, PR China.
    Ning, Yujie
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Xi'an, PR China.
    Wang, Xi
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Xi'an, PR China.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Xi'an, PR China.
    Guo, Xiong
    School of Public Health, Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Xi'an, PR China.
    Gene expression profiles and molecular mechanism of cultured human chondrocytes' exposure to T-2 toxin and deoxynivalenol2017In: Toxicon, ISSN 0041-0101, E-ISSN 1879-3150, Vol. 140, p. 38-44Article in journal (Refereed)
    Abstract [en]

    T-2 toxin and deoxynivalenol (DON) are secondary metabolites produced by Fusarium fungi and are commonly found on food and feed. Although T-2 toxin and DON have been suggested as the etiology of Kashin-Beck disease (KBD), an endemic osteochondropathy, little is known about the mechanism when human chondrocytes are exposed to T-2 toxin and DON. The purpose of this study is to identify the gene expression differences and underlying molecular changes modulated by T-2 toxin and DON in vitro in human chondrocytes. After the experiments of cell viability, the gene expression profiles were analyzed in cells that were treated with 0.01 μg/ml T-2 toxin and 1.0 μg/ml DON for 72 h by Affymetrix Human Gene Chip. The array results showed that 882 and 2118 genes were differentially expressed for T-2 toxin and DON exposure, respectively. Enrichment analysis revealed that diverse cellular processes including DNA damage, cell cycle regulation and metabolism of extracellular matrix were affected when human chondrocytes were exposed to T-2 toxin and DON. These results demonstrate the gene expression differences and molecular mechanism of cultured human chondrocytes exposure to T-2 toxin and DON, and provide a new insight into future research in the etiology of KBD.

  • 1260. Yang, Lei
    et al.
    Zhao, Guang-Hui
    Liu, Huan
    Wang, Xi
    Guo, Xiong
    Lammi, Mikko J
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Health Science Center, Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Xi’an, People’s Republic of China.
    Field synopsis and meta-analyses of genetic epidemiological evidence for Kashin-Beck disease, an endemic osteoarthropathy in China2016In: Molecular Genetics and Genomics, ISSN 1617-4615, E-ISSN 1617-4623, Vol. 291, no 5, p. 1823-1833, article id 27256326Article in journal (Refereed)
    Abstract [en]

    Kashin-Beck disease (KBD) is a chronic degenerative osteoarthropathy with unclear etiology. To provide current evidence supporting a genetic predisposition for KBD, we conducted a systematic review and meta-analysis of published literature on the genetic epidemiology of KBD. The PubMed, China National Knowledge Infrastructure and Wan Fang Data were searched up to August 2015 for articles published in English and Chinese. Genome-wide and exome sequencing, linkage, and case-control association studies for any genetic variants associated with KBD were included. Meta-analysis was performed for all single nucleotide polymorphisms (SNPs) that were evaluated in two or more studies. The effect size was summarized as odds ratios (ORs) with 95 % confidence intervals (CIs) by fixed and random effects models. A total of 24 articles were systematically reviewed. Eleven short tandem repeats on chromosomes 2, 11 and 12, 34 SNPs in 12 genes, as well as copy number variant 452 were identified as KBD susceptibility factors in individual studies. The meta-analysis of the GPX1 rs1050450, DIO2 rs225014, TrxR2 rs5748469 and HLA-DRB1 rs7745040 failed to reveal any associations with KBD. However, the meta-analysis of HLA-DRB1 rs9275295 allele A was associated with KBD (OR = 1.737, 95 % CI: 1.002-3.012). In addition, seven haplotypes in GPX1, GPX4, HLA-DRB1 and GDF5 genes also showed significant associations with KBD. In conclusions, our study could identify a number of genetic markers associated with KBD. However, the evidence does not currently support a strong association between the specific variants and KBD because of the limited number of studies, and in the future, more rigorous studies are needed to confirm KBD's links with these variants.

  • 1261.
    Yang, Lingling
    et al.
    State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
    Di, Guohu
    State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
    Qi, Xia
    State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
    Qu, Mingli
    State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
    Wang, Yao
    State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
    Duan, Haoyun
    State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Xie, Lixin
    State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
    Zhou, Qingjun
    State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
    Substance P promotes diabetic corneal epithelial wound healing through molecular mechanisms mediated via the neurokinin-1 receptor.2014In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 63, no 12, p. 4262-4274Article in journal (Refereed)
    Abstract [en]

    Substance P (SP) is a neuropeptide, predominantly released from sensory nerve fibers, with a potentially protective role in diabetic corneal epithelial wound healing. However, the molecular mechanism remains unclear. We investigated the protective mechanism of SP against hyperglycemia-induced corneal epithelial wound healing defects, using type 1 diabetic mice and high glucose-treated corneal epithelial cells. Hyperglycemia induced delayed corneal epithelial wound healing, accompanied with attenuated corneal sensation, mitochondrial dysfunction, and impairments of Akt-, EGFR-, and Sirt1-activation, as well as decreased reactive oxygen species (ROS) scavenging capacity. However, SP application promoted the epithelial wound healing, the recovery of corneal sensation, the improvement of mitochondrial function, and the reactivation of Akt, EGFR and Sirt1, as well as increased ROS scavenging capacity, in both diabetic mouse corneal epithelium and high glucose-treated corneal epithelial cells. The promotion of SP on diabetic corneal epithelial healing was completely abolished by a NK-1 receptor antagonist. Moreover, the subconjunctival injection of NK-1 receptor antagonist also caused diabetic corneal pathological changes in normal mice. In conclusion, the results suggest that SP-NK-1 receptor signaling plays a critical role in the maintenance of corneal epithelium homeostasis, and that SP signaling through the NK-1 recssssseptor contributes to the promotion of diabetic corneal epithelial wound healing by rescued activation of Akt, EGFR, and Sirt1, improvement of mitochondrial function, and increased ROS scavenging capacity.

  • 1262. Yang, Lingling
    et al.
    Qu, Mingli
    Wang, Yao
    Duan, Haoyun
    Chen, Peng
    Wang, Ye
    Shi, Weiyun
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Zhou, Qingjun
    Trichostatin A Inhibits Transforming Growth Factor-beta-Induced Reactive Oxygen Species Accumulation and Myofibroblast Differentiation via Enhanced NF-E2-Related Factor 2-Antioxidant Response Element Signaling2013In: Molecular Pharmacology, ISSN 0026-895X, E-ISSN 1521-0111, Vol. 83, no 3, p. 671-680Article in journal (Refereed)
    Abstract [en]

    Trichostatin A (TSA) has been shown to prevent fibrosis in vitro and in vivo. The present study aimed at investigating the role of reactive oxygen species (ROS) scavenging by TSA on transforming growth factor-beta (TGF-beta)-induced myofibroblast differentiation of corneal fibroblasts in vitro. Human immortalized corneal fibroblasts were treated with TGF-beta in the presence of TSA, the NAD(P) H oxidase inhibitor diphenyleneiodonium (DPI), the antioxidant N-acetyl-cysteine (NAC), the NF-E2-related factor 2-antioxidant response element (Nrf2-ARE) activator sulforaphane, or small interfering RNA. Myofibroblast differentiation was assessed by alpha-smooth muscle actin (alpha-SMA) expression, F-actin bundle formation, and collagen gel contraction. ROS, H2O2, intracellular glutathione (GSH) level, cellular total antioxidant capacity, and the activation of Nrf2-ARE signaling were determined with various assays. Treatment with TSA and the Nrf2-ARE activator resulted in increased inhibition of the TGF-beta-induced myofibroblast differentiation as compared with treatment with DPI or NAC. Furthermore, TSA also decreased cellular ROS and H2O2 accumulation induced by TGF-beta, whereas it elevated intracellular GSH level and cellular total antioxidant capacity. In addition, TSA induced Nrf2 nuclear translocation and up-regulated the expression of Nrf2-ARE downstream antioxidant genes, whereas Nrf2 knockdown by RNA interference blocked the inhibition of TSA on myofibroblast differentiation. In conclusion, this study provides the first evidence implicating that TSA inhibits TGF-beta-induced ROS accumulation and myofibroblast differentiation via enhanced Nrf2-ARE signaling.

  • 1263.
    Yau, Wai-Lok
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Nguyen-Dinh, Van
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Larsson, Elin
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lindquist, Richard
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Överby, Anna K.
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Lundmark, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Model System for the Formation of Tick-Borne Encephalitis Virus Replication Compartments without Viral RNA Replication2019In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 93, no 18, article id e00292-19Article in journal (Refereed)
    Abstract [en]

    Flavivirus is a positive-sense, single-stranded RNA viral genus, with members causing severe diseases in humans such as tick-borne encephalitis, yellow fever, and dengue fever. Flaviviruses are known to cause remodeling of intracellular membranes into small cavities, where replication of the viral RNA takes place. Nonstructural (NS) proteins are not part of the virus coat and are thought to participate in the formation of these viral replication compartments (RCs). Here, we used tick-borne encephalitis virus (TBEV) as a model for the flaviviruses and developed a stable human cell line in which the expression of NS proteins can be induced without viral RNA replication. The model system described provides a novel and benign tool for studies of the viral components under controlled expression levels. We show that the expression of six NS proteins is sufficient to induce infection-like dilation of the endoplasmic reticulum (ER) and the formation of RC-like membrane invaginations. The NS proteins form a membrane-associated complex in the ER, and electron tomography reveals that the dilated areas of the ER are closely associated with lipid droplets and mitochondria. We propose that the NS proteins drive the remodeling of ER membranes and that viral RNA, RNA replication, viral polymerase, and TBEV structural proteins are not required. IMPORTANCE TBEV infection causes a broad spectrum of symptoms, ranging from mild fever to severe encephalitis. Similar to other flaviviruses, TBEV exploits intracellular membranes to build RCs for viral replication. The viral NS proteins have been suggested to be involved in this process; however, the mechanism of RC formation and the roles of individual NS proteins remain unclear. To study how TBEV induces membrane remodeling, we developed an inducible stable cell system expressing the TBEV NS polyprotein in the absence of viral RNA replication. Using this system, we were able to reproduce RC-like vesicles that resembled the RCs formed in flavivirus-infected cells, in terms of morphology and size. This cell system is a robust tool to facilitate studies of flavivirus RC formation and is an ideal model for the screening of antiviral agents at a lower biosafety level.

  • 1264.
    Yelhekar, Tushar
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Chloride Homeostasis in Central Neurons2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The overall aim of the present thesis is to clarify the control of intracellular chloride homeostasis in central neurons, because of the critical role of chloride ions (Cl) for neuronal function. Normal function of the central nervous system (CNS) depends on a delicate balance between neuronal excitation and inhibition. Inhibition is, in the adult brain, most often mediated by the neurotransmitter γ-aminobutyric acid (GABA). GABA may, however, in some cases cause excitation. GABA acts by activating GABA type A receptors (GABAARs), which are ion channels largely permeable to Cl. The effect of GABAAR-mediated neuronal signaling - inhibitory or excitatory - is therefore mainly determined by the Cl gradient across the membrane. This gradient varies with neuronal activity and may be altered in pathological conditions. Thus, understanding Cl regulation is important to comprehend neuronal function. This thesis is an attempt to clarify several unknown aspects of neuronal Cl regulation. For such clarification, a sufficiently sensitive method for measuring the intracellular Cl concentration, [Cl]i, is necessary. In the first study of this thesis, we examined two electrophysiological methods commonly used to estimate [Cl]i. Both methods, here called the interpolation and the voltage-ramp method, depend on an estimate of the Cl equilibrium potential from the current-voltage relation of GABA- or glycine-evoked Cl currents. Both methods also provide an estimate of the membrane Cl conductance, gCl. With a combination of computational and electrophysiological techniques, we showed that the most common (interpolation) method failed to detect changes in [Cl]i and gCl during prolonged GABA application, whereas the voltage-ramp method accurately detected such changes. Our analysis also provided an explanation as to why the two methods differ. In a second study, we clarified the role of the extracellular matrix (ECM) for the distribution of Cl across the cell membrane of neurons from rat brain. It was recently proposed that immobile charges located within the ECM, rather than as previously thought cation-chloride transporter proteins, determine the low [Cl]i which is critical to GABAAR-mediated inhibition. By using electrophysiological techniques to measure [Cl]i, we showed that digestion of the ECM decreases the expression and function of the neuron-specific K+ Cl cotransporter 2 (KCC2), which normally extrudes Cl- from the neuron, thus causing an increase in resting [Cl]i. As a result of ECM degradation, the action of GABA may be transformed from inhibitory to excitatory. In a third study, we developed a method for quantifying the largely unknown resting Cl (leak) conductance, gCl, and examined the role of gCl for the neuronal Cl homeostasis. In isolated preoptic neurons from rat, resting gCl was about 6 % of total resting conductance, to a major part due to spontaneously open GABAARs and played an important role for recovery after a high Cl load. We also showed that spontaneous, impulse-independent GABA release can significantly enhance recovery when the GABA responses are potentiated by the neurosteroid allopregnanolone. In a final commentary, we formulated the mathematical relation between Cl conductance, KCC2-mediated Cl extrusion capacity and steady-state [Cl]i. In summary, the present thesis (i) clarifies how well common electrophysiological methods describe [Cl]i and gCl, (ii) provides a novel method for quantifying gCl in cell membranes and (iii) clarifies the roles of the ECM, ion channels and ion transporters in the control of [Cl]i homeostasis and GABAAR-mediated signaling in central neurons. 

  • 1265.
    Yelhekar, Tushar D.
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Druzin, Michael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Johansson, Staffan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Contribution of Resting Conductance, GABA(A)-Receptor Mediated Miniature Synaptic Currents and Neurosteroid to Chloride Homeostasis in Central Neurons2017In: eNeuro, ISSN 2373-2822, Vol. 4, no 2, article id e0019Article in journal (Refereed)
    Abstract [en]

    Maintenance of a low intraneuronal Cl- concentration, [Cl-](i), is critical for inhibition in the CNS. Here, the contribution of passive, conductive Cl- flux to recovery of [Cl-](i) after a high load was analyzed in mature central neurons from rat. A novel method for quantifying the resting Cl- conductance, important for [Cl-](i) recovery, was developed and the possible contribution of GABAA and glycine receptors and of ClC-2 channels to this conductance was analyzed. The hypothesis that spontaneous, action potential-independent release of GABA is important for [Cl-](i) recovery was tested. [Cl-](i) was examined by gramicidin-perforated patch recordings in medial preoptic neurons. Cells were loaded with Cl- by combining GABA or glycine application with a depolarized voltage, and the time course of [Cl-](i) was followed by measurements of the Cl- equilibrium potential, as obtained from the current recorded during voltage ramps combined with GABA or glycine application. The results show that passive Cl- flux contributes significantly, in the same order of magnitude as does K+-Cl- cotransporter 2 (KCC2), to [Cl-](i) recovery and that Cl- conductance accounts for similar to 6% of the total resting conductance. A major fraction of this resting Cl- conductance is picrotoxin (PTX)-sensitive and likely due to open GABAA receptors, but ClC-2 channels do not contribute. The results also show that when the decay of GABAA receptor-mediated miniature postsynaptic currents (minis) is slowed by the neurosteroid allopregnanolone, such minis may significantly quicken [Cl-](i) recovery, suggesting a possible steroid-regulated role for minis in the control of Clhomeostasis.

  • 1266.
    Yelhekar, Tushar D.
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Druzin, Michael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Karlsson, Urban
    Blomqvist, Erii
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Johansson, Staffan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    How to Properly Measure a Current-Voltage Relation? -Interpolation vs. Ramp Methods Applied to Studies of GABA(A) Receptors2016In: Frontiers in Cellular Neuroscience, ISSN 1662-5102, E-ISSN 1662-5102, Vol. 10, article id 10Article in journal (Refereed)
    Abstract [en]

    The relation between current and voltage, I-V relation, is central to functional analysis of membrane ion channels. A commonly used method, since the introduction of the voltage-clamp technique, to establish the I-V relation depends on the interpolation of current amplitudes recorded at different steady voltages. By a theoretical computational approach as well as by experimental recordings from GABA(A) receptor mediated currents in mammalian central neurons, we here show that this interpolation method may give reversal potentials and conductances that do not reflect the properties of the channels studied under conditions when ion flux may give rise to concentration changes. Therefore, changes in ion concentrations may remain undetected and conclusions on changes in conductance, such as during desensitization, may be mistaken. In contrast, an alternative experimental approach, using rapid voltage ramps, enable I-V relations that much better reflect the properties of the studied ion channels.

  • 1267.
    Yelhekar, Tushar
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Kuznetsova, Tatiana
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Malinina, Evgenya
    Ponimaskin, Evgeni
    Dityatev, Alexander
    Druzin, Michael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Johansson, Staffan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Extracellular Matrix Regulates Neuronal Chloride Concentration via K+-Cl--cotransporter 2Manuscript (preprint) (Other academic)
  • 1268.
    Ylärinne, Janne
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Production of neocartilage tissues using primary chondrocytes2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Hyaline cartilage is a highly specialized tissue, which plays an important role in the articulating joints of an individual. It provides the joints with a nearly frictionless, impact resisting surface to protect the ends of the articulating bones. Articular cartilage has a poor self-repair capacity and, therefore, it rarely heals back to normal after an injury. Overweight, injuries, overloading and genetic factors may initiate a degenerative disease of the joint called osteoarthritis.

    Osteoarthiritis is a major global public health issue. Currently, the most used treatment for large articular cartilage defects is joint replacement surgery. However, possibilities to replace this highly invasive operation with strategies based on tissue engineering are currently investigated. The idea of the tissue engineering is to optimize the use of the cells, biomaterials and culture conditions to regenerate a new functional tissue for the defect site.

    The goal of this thesis was to manufacture cartilage tissue in cell culture conditions in vitro. Bovine primary chondrocytes isolated from the femoral condyles were used in all the experiments for neocartilage production. The samples were collected for histology, gene expression level quantifications, and analyses of proteoglycan (PG) content and quality. The histological sections were stained for type II collagen and PGs, the quantitative RT-PCR was used to observe the relative expressions of aggrecan, Sox9, procollagen α2(I) and procollagen α1(II) genes. The PGs were quantified using a spectrophotometric method, and agarose gel electrophoresis was used to separate the PGs according to their size.

    In the two first studies, we optimized the culture conditions of in vitro scaffold-free culture technique to produce the native-type hyaline cartilage of a good quality. We found out that high glucose concentration and hypertonic medium at 20% oxygen tension promoted the best hyaline-like neocartilage tissue production. Glucosamine sulfate supplementation, low oxygen tension, 5 mM glucose concentration and a transient TGF-β3 supplementation were not beneficial for the neocartilage formation in the scaffold-free cell culture system.

    In the third study, we used these newly defined, optimized culture conditions to produce the neocartilage tissues in the HyStem™ and the HydroMatrix™ scaffold materials and we compared these tissues to the ones grown as scaffold-free control cultures. We noticed that there was no difference between the controls and the scaffolds, and occasionally the scaffold-free controls had produced better quality cartilage than the ones with the scaffolds. Overall, the neocartilage tissues were of good hyaline-like quality in the third study. Their extracellular matrix contents were close to the native cartilage, although the neotissues lacked the zonal organization typical to the normal articular cartilage. The tissues had the right components, but their ultrastructure differed from the native cartilage.

    In conclusion, we were able to optimize our in vitro neocartilage culture method further, and discovered a good combination of the culture conditions to produce hyaline-like cartilage of good quality. Surprisingly, the scaffold materials were not beneficial for the cartilage formation.

     

  • 1269.
    Ylärinne, Janne
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Qu, Chengjuan
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Health Science Center of Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, P. R. China.
    Comparison of the neocartilages generated in scaffolds and scaffold-free agarose gel supported primary chondrocyte culture: Generation of neocartilage in vitro Manuscript (preprint) (Other academic)
    Abstract [en]

    Objective: The present study was conducted to compare the neocartilages generated in scaffolds and scaffold-free, agarose gel-supported primary chondrocyte cultures.

    Design: Six million bovine primary chondrocytes were embedded in HyStem™ or HydroMatrix™ scaffolds, or scaffold-free in chondrocyte culture medium, and then loaded to agarose gel supported culture wells. Neocartilages were grown in the presence of hypertonic high glucose DMEM medium in 37 °C incubator at 20% O2 and 5% CO2 for one, three or six weeks. By the end of culture periods, the formed tissues were analyzed by histological staining for proteoglycans (PGs) and type II collagen, gene expression measurements of chondrocyte-specific genes aggrecan, Sox9 and procollagen α1(II), and procollagen α2(I) were performed using quantitative RT-PCR, and analyses of PG contents and structure were conducted by spectrophotometric and agarose gel electrophoretic methods, respectively.

    Results: The neocartilage generated in scaffold-free cultures appeared slightly bigger in size than in HyStem™- or HydroMatrix™-containing scaffolds. Histology visualized that the PGs and type II collagen were abundantly present in both in scaffold-free and scaffold-containing tissues. The PG content gradually increased following the culture period. However, the mRNA expression levels of the cartilage-specific genes of aggrecan, procollagen α1(II) and Sox9 gradually decreased following culture period, while procollagen α2(I) levels increased.

    Conclusions: After six weeks cultivations, the PG concentrations in neocartilage tissues manufactured with HyStem™ or HydroMatrix™ scaffolds, and in scaffold-free agarose gel-supported cell cultures, were similar to native cartilage. No obvious benefits could be seen on the extracellular matrix assembly in HyStem™ or HydroMatrix™ scaffolds cultures.

  • 1270.
    Ylärinne, Janne
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Xi’an Jiaotong Univ., Xi'an, China.
    HyStemTM and HydroMatrixTM scaffolds for articular cartilage tissue engineering2016In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 24, p. S466-S466Article in journal (Other academic)
    Abstract
  • 1271.
    Ylärinne, Janne
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, P. R. China.
    Scaffold-free approach produces neocartilage tissue of similar quality as the use of HyStem™ and Hydromatrix™ scaffolds2017In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 28, no 4, article id 59Article in journal (Refereed)
    Abstract [en]

    Numerous biomaterials are being considered for cartilage tissue engineering, while scaffold-free systems have also been introduced. Thus, it is important to know do the scaffolds improve the formation of manufactured neocartilages. This study compares scaffold-free cultures to two scaffold-containing ones. Six million bovine primary chondrocytes were embedded in HyStem™ or HydroMatrix™ scaffolds, or suspended in scaffold-free chondrocyte culture medium, and then loaded into agarose gel supported culture well pockets. Neocartilages were grown in the presence of hypertonic high glucose DMEM medium for up to 6 weeks. By the end of culture periods, the formed tissues were analyzed by histological staining for proteoglycans (PGs) and type II collagen, gene expression measurements of aggrecan, Sox9, procollagen α1(II), and procollagen α2(I) were performed using quantitative RT-PCR, and analyses of PG contents and structure were conducted by spectrophotometric and agarose gel electrophoretic methods. Histological stainings showed that the PGs and type II collagen were abundantly present in both the scaffold-free and the scaffold-containing tissues. The PG content gradually increased following the culture period. However, the mRNA expression levels of the cartilage-specific genes of aggrecan, procollagen α1(II) and Sox9 gradually decreased following culture period, while procollagen α2(I) levels increased. After 6-week-cultivations, the PG concentrations in neocartilage tissues manufactured with HyStem™ or HydroMatrix™ scaffolds, and in scaffold-free agarose gel-supported cell cultures, were similar to native cartilage. No obvious benefits could be seen on the extracellular matrix assembly in HyStem™ or HydroMatrix™ scaffolds cultures.

  • 1272.
    Yu, F
    et al.
    Pennsylvania State University.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Larsson, L
    Human single masseter muscle fibers contain unique combinations of myosin and myosin binding protein C isoforms2002In: Journal of Muscle Research and Cell Motility, ISSN 0142-4319, E-ISSN 1573-2657, Vol. 23, no 4, p. 317-326Article in journal (Refereed)
    Abstract [en]

    Striated craniofacial and limb muscles differ in their embryological origin, regulatory program during myogenesis, and innervation. In an attempt to explore the effects of these differences on the striated muscle phenotype in humans, the expression of myosin and myosin-associated thick filament proteins were studied at the single fiber level both in the human jaw-closing masseter muscle and in two limb muscles (biceps brachii and quadriceps femoris muscles). In the masseter, unique combinations of myosin heavy chain (MyHC) and myosin binding protein C (MyBP-C) isoforms were observed at the single fiber level. Compared to the limb muscles, the MyHC isoform expression was more complex in the masseter while the opposite was observed for MyBP-C. In limb muscles, a coordinated expression of three MyHC and three MyBP-C isoforms were observed, i.e., single fibers contained one or two MyHC isoforms, and up to three MyBP-C isoforms. Also, the relative content of the different MyBP-C isoforms correlated with the MyHC isoform expression. In the masseter, on the other hand, up to five different MyHC isoforms could be observed in the same fiber, but only one MyBP-C isoform was identified irrespective MyHC isoform expression. This MyBP-C isoform had a migration rate similar to the slow MyBP-C isoform in limb muscle fibers. In conclusion, a unique myofibrillar protein isoform expression was observed in the human masseter muscle fibers, suggesting significant differences in structural and functional properties between muscle fibers from human masseter and limb muscles.

  • 1273. Yu, Fang Fang
    et al.
    Lin, Xia Lu
    Yang, Lei
    Liu, Huan
    Wang, Xi
    Fang, Hua
    Lammi, Mikko J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an 710061, Shaanxi, China.
    Guo, Xiong
    Comparison of T-2 Toxin and HT-2 Toxin Distributed in the Skeletal System with That in Other Tissues of Rats by Acute Toxicity Test2017In: Biomedical and environmental sciences, ISSN 0895-3988, E-ISSN 2214-0190, Vol. 30, no 11, p. 851-854Article in journal (Refereed)
    Abstract [en]

    Twelve healthy rats were divided into the T-2 toxin group receiving gavage of 1 mg/kg T-2 toxin and the control group receiving gavage of normal saline. Total relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system (thighbone, knee joints, and costal cartilage) were significantly higher than those in the heart, liver, and kidneys (P < 0.05). The relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system (thighbone and costal cartilage) were also significantly higher than those in the heart, liver, and kidneys. The rats administered T-2 toxin showed rapid metabolism compared with that in rats administered HT-2 toxin, and the metabolic conversion rates in the different tissues were 68.20%-90.70%.

  • 1274.
    Yu, Fang-Fang
    et al.
    Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, China.
    Lin, Xia-Lu
    Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, China.
    Wang, Xi
    Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, China.
    Liu, Huan
    Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, China.
    Yang, Lei
    Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, China.
    Goldring, Mary B.
    Hospital for Special Surgery, Weill Cornell Medical College, New York, NY, USA.
    Lammi, Mikko J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, China.
    Guo, Xiong
    Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, China.
    Selenium promotes metabolic conversion of T-2 toxin to HT-2 toxin in cultured human chondrocytes2017In: Journal of Trace Elements in Medicine and Biology, ISSN 0946-672X, E-ISSN 1878-3252, Vol. 44, p. 218-224Article in journal (Refereed)
    Abstract [en]

    To explore the metabolism of T-2 toxin in human chondrocytes (HCs) and determine the impact of selenium supplementation. For determination of cytotoxicity using the MTT assay, optical density values were read with an automatic enzyme-linked immunosorbent assay reader at 510nm. Cell survival was calculated and the cytotoxicity estimated. To identify the metabolites of T-2 toxin, the medium supernatants and C28/I2 cells were analyzed by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) separately. For HPLC-MS/MS, the mobile phase A was water and phase B was 98% methanol. The gradient for the elution was: 0-0.5min, 50% of B; 0.5-2.0min, 100% of B; 2.0-3.5min, 100% of B; 3.6-6min, 50% of B. T-2 toxin increased the toxicity to C28/I2 cells significantly in a dose- and time-dependent manner (viability range 91.5-22.0%). Supplementation with selenium (100ng/mL) could increase the cell viability after the 24h incubation. The concentration of T-2 toxin in the cell medium decreased from 20 to 6.67±1.02ng/mL, and the concentration of HT-2 toxin increased from 0 to 6.88±1.23ng/mL during the 48h incubation, whereas the relative concentration of T-2 toxin in cells increased from 0 to 12.80±1.84ng/g. Supplementary selenium in the HCs cultures reduced the cytotoxicity induced by T-2 toxin significantly, and was associated with rapid conversion of T-2 toxin in the culture medium to HT-2 toxin. T-2 toxin was more toxic to HCs than HT-2 toxin at equivalent concentrations. HT-2 toxin was a detectable metabolite of T-2 toxin in cultured HCs, and selenium enhanced the metabolic conversion of T-2 toxin, reducing its cytotoxicity to HCs.

  • 1275.
    Yu, Fang-Fang
    et al.
    Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, China.
    Zhang, Yan-Xiang
    Department of Orthopedics, Baoji People’s Hospital, Baoji, China.
    Zhang, Lian-He
    Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, China.
    Li, Wen-Rong
    Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, China.
    Guo, Xiong
    Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, China.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi’an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi’an, China.
    Identified molecular mechanism of interaction between environmental risk factors and differential expression genes in cartilage of Kashin-Beck disease2016In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 95, no 52, article id e5669Article in journal (Refereed)
    Abstract [en]

    As environmental risk factors (ERFs) play an important role in the pathogenesis of Kashin-Beck disease (KBD), it is important to identify the interaction between ERFs and differentially expression genes (DEGs) in KBD. The environmental response genes (ERGs) were analyzed in cartilage of KBD in comparison to normal controls.We searched 5 English and 3 Chinese databases from inception to September 2015, to identify case-control studies that examined ERFs for KBD using integrative meta-analysis and systematic review. Total RNA was isolated from articular cartilage of KBD patients and healthy controls. Human whole genome microarray chip (Agilent) was used to analyze the amplified, labeled, and hybridized total RNA, and the validated microarray data were partially verified using real-time quantitative polymerase chain reaction (qRT-PCR). The ERGs were derived from the Comparative Toxicogenomics Database. The identified ERGs were subjected to KEGG pathway enrichment, biological process (BP), and interaction network analyses using the Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.7, and STRING.The trace elements (selenium and iodine), vitamin E, and polluted grains (T-2 toxin/HT-2 toxin, deoxynivalenol, and nivalenol) were identified as the ERFs for KBD using meta-analysis and review. We identified 21 upregulated ERGs and 7 downregulated ERGs in cartilage with KBD compared with healthy controls, which involved in apoptosis, metabolism, and growth and development. KEGG pathway enrichment analysis found that 2 significant pathways were involved with PI3K-Akt signaling pathway and P53 signaling pathway, and gene ontology function analysis found 3 BPs involved with apoptosis, death, and cell death in KBD cartilage.According to previous results and our own research, we suggest that the trace element selenium and vitamin E induce PI3K-Akt signaling pathway and the mycotoxins (T-2 toxin/HT-2 toxin and DON) induce P53 signaling pathway, contributing to the development of KBD, and chondrocyte apoptosis and cell death.

  • 1276.
    Yu, J-G
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Fürst, D. O.
    Thornell, Lars-Eric
    The mode of myofibril remodelling in human skeletal muscle affected by DOMS induced by eccentric contractions.2003In: Histochemistry and Cell Biology, ISSN 0948-6143, Vol. 119, no 5, p. 383-393Article in journal (Refereed)
  • 1277.
    Yu, J-G
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Malm, Christer
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Thornell, Lars-Eric
    Eccentric contractions leading to DOMS do not cause loss of desmin nor fibre necrosis in human muscle.2002In: Histochemistry and Cell Biology, ISSN 0948-6143, Vol. 118, no 1, p. 29-34Article in journal (Refereed)
  • 1278.
    Yu, J-G
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Thornell, Lars-Eric
    Desmin and actin alterations in human muscles affected by delayed onset muscle soreness: a high resolution immunocytochemical study.2002In: Histochemistry and Cell Biology, ISSN 0948-6143, Vol. 118, no 2, p. 171-179Article in journal (Refereed)
  • 1279.
    Yu, J-G
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Evidence of transient increased permeability of sarcolemma upon eccentric exercise inducing delayed onset muscle soreness.Manuscript (Other academic)
  • 1280.
    Yu, J-G
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Thornell, Lars-Eric
    Ultrastructural alterations in human muscles with DOMS revisited: Evidence for myofibril remodeling as opposed to myofibril damage.Manuscript (Other academic)
  • 1281.
    Yu, Ji-Guo
    Umeå University, Faculty of Medicine, Integrative Medical Biology.
    Re-evaluation of exercise-induced muscle soreness: an immunohistochemical and ultrastructural study2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Delayed onset muscle soreness (DOMS) is a familiar experience for the elite and novice athletes. Symptoms can range from muscle tenderness to severe deliberating pain. It is generally believed that eccentric contractions produce higher tension on muscle fibres and connective tissues than concentric and isometric contractions. This higher mechanical stress induces initial injury, and subsequent damage is linked to inflammatory process and to changes in the excitation-contraction coupling within the muscles. Classically myofibrillar ultrastrctural changes in DOMS muscles are mainly related with myofibrillar Z-disc. Z-disc streaming and broadening have long been deemed as the hallmarks of DOMS muscles. Recent studies on rabbit models have shown a rapid loss of the intermediate filament protein desmin after eccentric contractions and this was believed to be the initial event which triggers a subsequent muscle fibre necrosis. Even though numerous studies have been conducted on both human muscles and animal models following eccentric exercise, the mechanisms responsible for the perception of DOMS have not been clearly identified.

    To re-evaluate the exercise-induced muscle soreness with respect to the muscle fibre structural changes, in the present study three different modes of eccentric exercise were used as a model to introduce DOMS in healthy young subjects. Biopsies from the soleus muscle and vastus lateralis muscle were taken from control subjects and those who had taken part in the exercise, at different time intervals after exercise. The biopsies were analyzed with general histology, enzymehistochemistry, immunohistochemistry and electronmicroscopy.

    All the three exercise protocols induced DOMS, which reached its peak value at 24-48 hour post exercise. Examination of the biopsies taken after the three exercise modes showed no loss of desmin or fibre necrosis of any biopsy. However, in biopsies taken 1 hour post exercise, some influx of fibrinogen into muscle fibres was observed. Despite that, the sarcolemma integrity revealed by stainings with dystrophin and laminin was seemingly not destroyed. Further analysis of the biopsies taken after the downstairs running with high-resolution immunohistochemistry revealed the following alterations: 1) F-actin and desmin were in much greater amounts and distributed differently from normal muscle; 2) alpha-actinin, nebulin and titin were initially lacking in focal areas and were subsequently reappearing. These changes were mainly observed in the 2-3 days and 7-8 days post exercise biopsies. The staining patterns were proposed to represent different stages of sarcomere formation. These findings therefore support the suggestion that myofibrils in muscles subjected to eccentric contractions adapt to unaccustomed activity by the addition of new sarcomeres. Electronmicroscopy showed ultrastructural changes also mainly in biopsies taken 2-3 days and 7-8 days post exercise. These changes were classified into four types on bases of their different staining patterns. For each of the four types of changes, there was a corresponding type of changes revealed by the immunohistochemical method. It was concluded that alterations revealed by electronmicroscopy were suggestive of myofibrillar remodeling rather than the conventionally suggested injury.

    The present study will change the dogma that myofibrillar disruption/damage is a hallmark of DOMS. The findings of this study is of clinical importance as the myofibrils contrary to becoming weakened, are reinforced by cytoskeletal elements during the addition of new sarcomeres. The latter gives for the first time a mechanistic explanation for the lack of further damage upon additional exercise (second bout effect). Furthermore, the current methods of analysis of biopsies from eccentric exercised subjects can be used as an in situ model to analyze the molecular changes taking place in the muscle fibres affected by DOMS.

  • 1282.
    Yu, Ji-Guo
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Bonnerud, Patrik
    Department of Health Sciences, Luleå University of Technology, Luleå.
    Eriksson, Anders
    Department of Health Sciences, Luleå University of Technology, Luleå.
    Stål, Per S.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Tegner, Yelverton
    Department of Health Sciences, Luleå University of Technology, Luleå.
    Malm, Christer
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Effects of long term supplementation of anabolic androgen steroids on human skeletal muscle2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 9, article id e105330Article in journal (Refereed)
    Abstract [en]

    The effects of long-term (over several years) anabolic androgen steroids (AAS) administration on human skeletal muscle are still unclear. In this study, seventeen strength training athletes were recruited and individually interviewed regarding self-administration of banned substances. Ten subjects admitted having taken AAS or AAS derivatives for the past 5 to 15 years (Doped) and the dosage and type of banned substances were recorded. The remaining seven subjects testified to having never used any banned substances (Clean). For all subjects, maximal muscle strength and body composition were tested, and biopsies from the vastus lateralis muscle were obtained. Using histochemistry and immunohistochemistry (IHC), muscle biopsies were evaluated for morphology including fiber type composition, fiber size, capillary variables and myonuclei. Compared with the Clean athletes, the Doped athletes had significantly higher lean leg mass, capillary per fibre and myonuclei per fiber. In contrast, the Doped athletes had significantly lower absolute value in maximal squat force and relative values in maximal squat force (relative to lean body mass, to lean leg mass and to muscle fiber area). Using multivariate statistics, an orthogonal projection of latent structure discriminant analysis (OPLS-DA) model was established, in which the maximal squat force relative to muscle mass and the maximal squat force relative to fiber area, together with capillary density and nuclei density were the most important variables for separating Doped from the Clean athletes (regression  =  0.93 and prediction  =  0.92, p<0.0001). In Doped athletes, AAS dose-dependent increases were observed in lean body mass, muscle fiber area, capillary density and myonuclei density. In conclusion, long term AAS supplementation led to increases in lean leg mass, muscle fiber size and a parallel improvement in muscle strength, and all were dose-dependent. Administration of AAS may induce sustained morphological changes in human skeletal muscle, leading to physical performance enhancement.

  • 1283.
    Yu, Ji-Guo
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Carlsson, Lena
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Evidence for myofibril remodeling as opposed to myofibril damage in human muscles with DOMS: an ultrastructural and immunoelectron microscopic study.2004In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 121, no 3, p. 219-227Article in journal (Refereed)
    Abstract [en]

    The myofibrillar and cytoskeletal alterations observed in delayed onset muscle soreness (DOMS) caused by eccentric exercise are generally considered to represent damage. By contrast our recent immunohistochemical studies suggested that the alterations reflect myofibrillar remodeling (Yu and Thornell 2002; Yu et al. 2003). In the present study the same human muscle biopsies were further analyzed with transmission electron microscopy and immunoelectron microscopy. We show that the ultrastructural hallmarks of DOMS, Z-disc streaming, Z-disc smearing, and Z-disc disruption were present in the biopsies and were significantly more frequent in biopsies taken 2-3 days and 7-8 days after exercise than in those from controls and 1 h after exercise. Four main types of changes were observed: amorphous widened Z-discs, amorphous sarcomeres, double Z-discs, and supernumerary sarcomeres. We confirm by immunoelectron microscopy that the main Z-disc protein alpha-actinin is not present in Z-disc alterations or in the links of electron-dense material between Z-discs in longitudinal register. These alterations were related to an increase of F-actin and desmin, where F-actin was present within the strands of amorphous material. Desmin, on the other hand, was seen in less dense regions of the alterations. Our results strongly support that the myofibrillar and cytoskeletal alterations, considered to be the hallmarks of DOMS, reflect an adaptive remodeling of the myofibrils.

  • 1284.
    Yu, Ji-Guo
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Fürst, Dieter O
    Department of Cell Biology, Institute for Biochemistry and Biology, University of Potsdam, Potsdam, Germany.
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    The mode of myofibril remodelling in human skeletal muscle affected by DOMS induced by eccentric contractions.2003In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 119, no 5, p. 383-93Article in journal (Refereed)
    Abstract [en]

    Myofibrillar Z-disc streaming and loss of the desmin cytoskeleton are considered the morphological hallmarks of eccentric contraction-induced injury. The latter is contradicted by recent studies where a focal increase of desmin was observed in biopsies taken from human muscles with DOMS. In order to determine the effects of eccentric contraction-induced alterations of the myofibrillar Z-disc, we examined the distribution of alpha-actinin, the Z-disc portion of titin and the nebulin NB2 region in relation to actin and desmin in DOMS biopsies. In biopsies taken 2-3 days and 7-8 days after exercise, we observed a significantly higher number of fibres showing focal areas lacking staining for alpha-actinin, titin and nebulin than in biopsies taken from control or 1 h after exercise. None of these proteins were part of Z-disc streamings but instead they were found in distinct patterns in areas characterised by altered staining for desmin and actin. These were preferentially seen in regions with increased numbers of sarcomeres in parallel myofibrils. We propose that these staining patterns represent different stages of sarcomere formation. These findings therefore support our previous suggestion that muscle fibres subjected to eccentric contractions adapt to unaccustomed activity by the addition of new sarcomeres.

  • 1285.
    Yu, Ji-Guo
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Liu, Jing-Xia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Carlsson, Lena
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Stål, Per S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Re-evaluation of sarcolemma injury and muscle swelling in human skeletal muscles after eccentric exercise2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 4, article id e62056Article in journal (Refereed)
    Abstract [en]

    The results regarding the effects of unaccustomed eccentric exercise on muscle tissue are often conflicting and the aetiology of delayed onset muscle soreness (DOMS) induced by eccentric exercise is still unclear. This study aimed to re-evaluate the paradigm of muscular alterations with regard to muscle sarcolemma integrity and fibre swelling in human muscles after voluntary eccentric exercise leading to DOMS. Ten young males performed eccentric exercise by downstairs running. Biopsies from the soleus muscle were obtained from 6 non-exercising controls, 4 exercised subjects within 1 hour and 6 exercised subjects at 2-3 days and 7-8 days after the exercise. Muscle fibre sarcolemma integrity, infiltration of inflammatory cells and changes in fibre size and fibre phenotype composition as well as capillary supply were examined with specific antibodies using enzyme histochemistry and immunohistochemistry. Although all exercised subjects experienced DOMS which peaked between 1.5 to 2.5 days post exercise, no significant sarcolemma injury or inflammation was detected in any post exercise group. The results do not support the prevailing hypothesis that eccentric exercise causes an initial sarcolemma injury which leads to subsequent inflammation after eccentric exercise. The fibre size was 24% larger at 7-8 days than at 2-3 days post exercise (p<0.05). In contrast, the value of capillary number per fibre area tended to decrease from 2-3 days to 7-8 days post exercise (lower in 5 of the 6 subjects at 7-8 days than at 2-3 days; p<0.05). Thus, the increased fibre size at 7-8 days post exercise was interpreted to reflect fibre swelling. Because the fibre swelling did not appear at the time that DOMS peaked (between 1.5 to 2.5 days post exercise), we concluded that fibre swelling in the soleus muscle is not directly associated with the symptom of DOMS.

  • 1286.
    Yu, Ji-Guo
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Malm, Christer
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Eccentric contractions leading to DOMS do not cause loss of desmin nor fibre necrosis in human muscle.2002In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 118, no 1, p. 29-34Article in journal (Refereed)
    Abstract [en]

    High force eccentric muscle contractions can result in delayed onset muscle soreness (DOMS), prolonged loss of muscle strength, decreased range of motion, muscle swelling and an increase of muscle proteins in the blood. At the ultrastructural level Z-line streaming and myofibrillar disruptions have been taken as evidence for muscle damage. In animal models of eccentric exercise-induced injury, disruption of the cytoskeleton and the sarcolemma of muscle fibres occurs within the first hour after the exercise, since a rapid loss of staining of desmin, a cytoskeletal protein, and the presence of fibronectin, a plasma and extracellular protein, are observed within the muscle fibres. In the present study, biopsies from subjects who had performed different eccentric exercises and had developed DOMS were examined. Our aim was to determine whether eccentric exercise leading to DOMS causes sarcolemmal disruption and loss of desmin in humans. Our study shows that even though the subjects had DOMS, muscle fibres had neither lost staining for desmin nor contained plasma fibronectin. This study therefore does not support previous conclusions that there is muscle fibre degeneration and necrosis in human skeletal muscle after eccentric exercise leading to DOMS. Our data are in agreement with the recent findings that there is no inflammatory response in skeletal muscle following eccentric exercise in humans. In combination, these findings should stimulate the search for other mechanisms explaining the functional and structural alterations in human skeletal muscle after eccentric exercise.

  • 1287.
    Yu, Ji-Guo
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Sewright, Kimberly
    Hubal, Monica
    Liu, Jing-Xia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Schwartz, Lawrence
    Hoffman, Eric
    Clarkson, Priscilla
    Investigation of gene expression in C(2)C(12) Myotubes following simvastatin application and mechanical strain2009In: Journal of Atherosclerosis and Thrombosis, ISSN 1880-3873, E-ISSN 1340-3478, Vol. 16, no 1, p. 21-29Article in journal (Refereed)
    Abstract [en]

    Aim: The 3-hydroxy-3methylgutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are the most effective prescribed drugs for lowering serum cholesterol; however, although statins are extremely safe medications and have brought significant benefits to patients with hypercholesterolemia, they have been shown to produce myalgia, cramps, exercise intolerance and fatigue. The aim of the study was to investigate the molecular mechanisms that may mediate statin myopathy.

    Methods: We used DNA microarray analysis to examine the changes in gene expression profiles induced by 1 hour and 6 hours of statin treatment on differentiated C(2)C(12) myotubes. Four genes were selected for analysis at the protein level using Western blot analysis on myotubes treated with statin with or without additional mechanical stretching.

    Results: Eighty-five genes exhibited more than a 2-fold up- or down-regulation in expression, of which 46 have known biological functions related primarily to transmembrane transport, signal transduction, cell growth/maintenance, protein metabolism, or apoptosis. At protein level, three of the four proteins were induced (Adrb1, Socs4 and Cflar) and one was repressed (Birc4). Changes in protein expression largely mirrored the changes in their corresponding transcripts, although the fold-change was less dramatic. The addition of imposed muscle fiber stretching did not exacerbate the expression of these genes at the protein level with the exception of Cflar, a pro-apoptotic protein.

    Conclusion: These data suggested that alterations in the expressions of some statin-regulated genes could be causative factors for statin toxicity in muscle. Repression of the anti-apoptosis gene (Birc4) and activation of the pro-apoptosis gene (Cflar) indicated that cell death may play an important role in statin-induced myopathy.

  • 1288.
    Yu, Ji-Guo
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Desmin and actin alterations in human muscles affected by delayed onset muscle soreness: a high resolution immunocytochemical study.2002In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 118, no 2, p. 171-9Article in journal (Refereed)
    Abstract [en]

    Lack of staining for desmin in muscles in animal models of eccentric exercise has been suggested to reflect disruption of the desmin intermediate filament network and proposed to cause disruption of the myofibrillar apparatus and deterioration of muscle fibers. In a recent study, we examined muscle biopsies from persons who had performed different eccentric exercise protocols, which induced delayed onset muscle soreness (DOMS). We were unable to verify that loss of staining for desmin was a feature of sore muscles. Nevertheless, we observed changes in the desmin cytoskeleton, but the meaning of the observations was not conclusive. In the present study, a high resolution immunocytochemical method was used to investigate the changes of desmin and actin in human muscles following a bout of eccentric exercise that lead to DOMS 2-3 days post-exercise. Biopsies were taken before exercise and 1 h and 2-3 and 7-8 days after exercise. Phalloidin, a ligand that labels filamentous actin, and anti-desmin antibodies were used to stain semithin (approximately 0.5 micro m) cryosections. At 1 h post-exercise, the staining of actin and desmin did not differ from the controls, whereas in biopsies taken 2-3 and 7-8 days after exercise, 12.5% (SD 5.8%) and 6.1% (SD 2.3%) fibers showed areas of increased staining for actin. Corresponding values for fibers with increased staining for both actin and desmin were 8.7% (SD 3.9%) and 11.4% (SD 4.6%), respectively. We suggest that the increased staining of actin and desmin reflects an increased synthesis of these proteins as part of an adaptation process following the unaccustomed eccentric exercise.

  • 1289. Zashikhin, A L
    et al.
    Sehlin, Janove
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Histology and Cell Biology.
    Bolduev, V A
    Agafonov, Iu V
    Organization of the muscular component of the lymphangion wall in different parts of the lymphatic bed2005In: Morfologiia, ISSN 1026-3543, Vol. 127, no 1, p. 29-32Article in journal (Other academic)
    Abstract [en]

    Complex comparative analysis of the organization of smooth muscle (SM) forming the wall of lymphatic vessels in bovine small intestinal mesenterium was performed using the methods of morphometry, quantitative histochemistry (including the analysis of nuclear DNA content, and cytoplasmic protein content) and electron microscopy. SM cells (SMC) isolated by dissociation were studied and were found to possess various levels of differentiation, associated with specific morphometric and metabolic characteristics. The structure of SMC population was shown to vary in both different parts of lymphatic bed and within the wall of an individual lymphangion. The results obtained indicate the cellular heteromorphism of lymphatic bed SM. The peculiarities of SM organization in lymphatic vessels are functionally dependent and are determined not only by the level of SM representation in their wall but also by the proportions of different SMC types.

  • 1290.
    Zashikhin, Andrei L
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Sehlin, Janove
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Barmina, Anastasia O
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    [Reactive changes in the smooth muscle tissue of the rat small intestine during experimental intestinal obstruction].2010In: Morfologiia (Saint Petersburg, Russia), ISSN 1026-3543, Vol. 137, no 2, p. 48-53Article in journal (Refereed)
    Abstract [ru]

    Using light, electron microscopy and immunohistochemical methods, the reactive transformation of smooth muscle tissue (SMT) was studied in the intestinal wall during the development of acute partial high intestinal obstruction. The material of small intestine was taken from 10 male rats in both the zone of ligature application, and proximal and distal zones, 3 cm distant from the ligation zone. The results of the study demonstrate that in partial intestinal obstruction, the nature of structural and functional SMT transformation was variable depending upon differences in functional and destructive loads. During these changes, the remodeling of smooth myocyte population was shown to be one of the mechanisms of SMT adaptation to the changing conditions of functioning. Immunohistochemical analysis found no changes in the pattern of expression of marker and phenotypic proteins in the intestinal zones studied during the dynamics of an experiment.

  • 1291.
    Zashikhin, Andrei
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Sehlin, Janove
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Visceral'naja gladkaja myšečnaja tkan'2001Book (Refereed)
  • 1292.
    Zashikhin, Andrey L
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Sehlin, Janove
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Barmina, Anastasia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Mechanisms of the contractile activity control in smooth muscle cells2010In: Morfologiia, ISSN 1026-3543, Vol. 138, no 6, p. 56-59Article in journal (Refereed)
  • 1293.
    Zeisig, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Ljung, B-O
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Immunohistochemical evidence of local production of catecholamines in cells of the muscle origins at the lateral and medial humeral epicondyles: of importance for the development of tennis and golfer's elbow?2009In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 43, no 4, p. 269-275Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Tennis elbow (TE) is a painful condition affecting the common extensor origin at the lateral humeral epicondyle. Colour Doppler examination has shown increased blood flow at this site and the sensory, and sympathetic innervation patterns have been delineated. However, it is not known whether there is local production of catecholamines and/or acetylcholine in this tissue, which is the case in patellar and Achilles tendinopathies. OBJECTIVE: To investigate the possible presence of local production of catecholamines and acetylcholine in non-neuronal cells (fibroblasts) in connective tissue at the muscle origin at the lateral humeral epicondyle in patients with TE. DESIGN: Immunohistochemical studies were performed on biopsies taken from the extensor origin in patients with TE and in pain-free controls. For reference purpose, biopsies from the flexor origin in patients with golfer's elbow (GE) were also studied. PATIENTS: Seven patients with TE and four patients with GE. Six healthy asymptomatic individuals served as controls. Method: Immunohistochemistry, using antibodies detecting synthesising enzymes for catecholamines (tyrosine hydroxylase; TH) and acetylcholine (choline acetyltransferase; ChAT). RESULTS: TH-like immunohistochemical reactions were seen in fibroblasts in four of the seven patients with TE and two of the four patients with GE. No such reactions were detected in controls (0/6). No ChAT reactions were seen in any of the investigated specimens. CONCLUSIONS: There is evidence of local, non-neuronal production of catecholamines, but not acetylcholine, in fibroblasts in the tissue at the muscle origin at the lateral and medial epicondyles in patients with TE and GE, respectively, which might have an influence on blood vessel regulation and pain mechanisms in these conditions.

  • 1294.
    Zhang, Cheng-Gang
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Anatomy.
    Ma, Jian-Jun
    Terenghi, Giorgio
    Mantovani, Cristina
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Anatomy. Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Hand Surgery.
    Phrenic nerve transfer in the treatment of brachial plexus avulsion: an experimental study of nerve regeneration and muscle morphology in rats.2004In: Microsurgery, ISSN 0738-1085, E-ISSN 1098-2752, Vol. 24, no 3, p. 232-240Article in journal (Refereed)
    Abstract [en]

    The regeneration of motor and sensory neurons and the morphological changes of the target muscle after phrenic nerve transfer were investigated in adult rats. Six months following nerve transfer, 326.0 +/- 16.31 phrenic motoneurons regenerated into musculocutaneous nerve, which is not different from the normal number of phrenic motoneurons. The regenerated motoneurons exhibited a 14% nonsignificant hypertrophy. Of the dorsal root ganglia (DRG) neurons, 255.8 +/- 45.26 regenerated, which was significantly lower than the number of normal phrenic DRG neurons. The regenerated phrenic DRG neurons showed a 24% close-to-significant atrophy. The target muscle fiber morphology changed considerably after reinnervation. The present results suggest that the phrenic nerve has very good regenerative ability in terms of its motoneurons and a relatively insufficient sensory neuronal regeneration.

  • 1295. Zhang, Cheng-Gang
    et al.
    Terenghi, Giorgio
    Mantovani, Cristina
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Anatomy.
    Neuronal survival, regeneration and musclemorphology after posterior C7 nerve transfer: an experimental study.2006In: J Plast Reconstr Aesthet Surg, ISSN 1748-6815, Vol. 59, no 7, p. 717-25Article in journal (Refereed)
    Abstract [en]

    C7 nerve transfer has been widely used in treating brachial plexus avulsion injuries. Little is known regarding the survival and regeneration of C7 motor and sensory neurons including their morphological changes after this procedure and also the possible change of muscle fibre phenotype. In this experimental study, the posterior division of C7 nerve was transferred to the musculocutaneous nerve ipsilaterally, and using fluorescent tracing techniques, the C7 spinal cord segment and dorsal root ganglion were found to contain 630.9 +/- 86.7 motor neurons and 3916.0 +/- 517.3 sensory neurons, respectively. Six months following transfer, 90% of the motor neurons and 78% of the sensory neurons survived and approximately 40% of them had regenerated and all displayed normal soma size. After posterior C7 transfer and reinnervation, the target muscles showed a percentage pattern of distribution and mean fibre diameters similar to those seen in normal biceps muscle. The present study suggests that the posterior C7 nerve transfer provides sufficient number of neurons and satisfactory results for regeneration to obtain an acceptable functional recovery.

  • 1296. Zhang, Cheng-Gang
    et al.
    Welin, Dag
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Novikov, Lev
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Kellerth, Jan-Olof
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Hart, Andrew McKay
    Motorneuron protection by N-acetyl-cysteine after ventral root avulsion and ventral rhizotomy2005In: British Journal of Plastic Surgery, ISSN 0007-1226, E-ISSN 1465-3087, Vol. 58, no 6, p. 765-773Article in journal (Refereed)
    Abstract [en]

    Motor recovery after proximal nerve injury remains extremely poor, despite advances in surgical care. Several neurobiological hurdles are implicated, the most fundamental being extensive cell death within the motorneuron pool. N-acetyl-cysteine almost completely protects sensory neurons after peripheral axotomy, hence its efficacy in protecting motorneurons after ventral root avulsion/rhizotomy was investigated. In adult rats, the motorneurons supplying medial gastrocnemius were unilaterally pre-labelled with retrograde tracer (true-blue/fluoro-gold), prior to L5 and 6 ventral root avulsion, or rhizotomy. Groups received either intraperitoneal N-acetyl-cysteine (ip, 150 or 750 mg/kg/day), immediate or delayed intrathecal N-acetyl-cysteine treatment (it, 2.4 mg/day), or saline; untreated animals served as controls. Either 4 (avulsion model) or 8 (rhizotomy model) weeks later, the pre-labelled motorneurons' mean soma area and survival were quantified. Untreated controls possessed markedly fewer motorneurons than normal due to cell death (avulsion 53% death; rhizotomy 26% death, P<0.01 vs. normal). Motorneurons were significantly protected by N-acetyl-cysteine after avulsion (ip 150 mg/kg/day 40% death; it 30% death, P<0.01 vs. no treatment), but particularly after rhizotomy (ip 150 mg/kg/day 17% death; ip 750 mg/kg/day 7% death; it 5% death, P<0.05 vs. no treatment). Delaying intrathecal treatment for 1 week after avulsion did not impair neuroprotection, but a 2-week delay was deleterious (42% death, P<0.05 vs. 1-week delay, 32% death). Treatment prevented the decrease in soma area usually found after both types of injury. N-acetyl-cysteine has considerable clinical potential for adjuvant treatment of major proximal nerve injuries, including brachial plexus injury, in order that motorneurons may survive until surgical repair facilitates regeneration.

  • 1297.
    Zhang, Feng'e
    et al.
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, China.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, China.
    Shao, Wanzhen
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, China.
    Zhang, Pan
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, China.
    Zhang, Yanan
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, China.
    Wei, Haiyan
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, China.
    Guo, Xiong
    School of Public Health, Health Science Center of Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an, China.
    Cytotoxic properties of HT-2 toxin in human chondrocytes: Could T3 inhibit toxicity of HT-2?2019In: Toxins, ISSN 2072-6651, E-ISSN 2072-6651, Vol. 11, no 11, p. E667-E667, article id 31731600Article in journal (Refereed)
    Abstract [en]

    Thyroid hormone triiodothyronine (T3) plays an important role in coordinated endochondral ossification and hypertrophic differentiation of the growth plate, while aberrant thyroid hormone function appears to be related to skeletal malformations, osteoarthritis, and Kashin-Beck disease. The T-2 toxin, present extensively in cereal grains, and one of its main metabolites, HT-2 toxin, are hypothesized to be potential factors associated with hypertrophic chondrocyte-related osteochondropathy, known as the Kashin-Beck disease. In this study, we investigated the effects of T3 and HT-2 toxin on human chondrocytes. The immortalized human chondrocyte cell line, C-28/I2, was cultured in four different groups: controls, and cultures with T3, T3 plus HT-2 and HT-2 alone. Cytotoxicity was assessed using an MTT assay after 24-h-exposure. Quantitative RT-PCR was used to detect gene expression levels of collagen types II and X, aggrecan and runx2, and the differences in runx2 were confirmed with immunoblot analysis. T3 was only slightly cytotoxic, in contrast to the significant, dose-dependent cytotoxicity of HT-2 alone at concentrations ≥ 50 nM. T3, together with HT-2, significantly rescued the cytotoxic effect of HT-2. HT-2 induced significant increases in aggrecan and runx2 gene expression, while the hypertrophic differentiation marker, type X collagen, remained unchanged. Thus, T3 protected against HT-2 induced cytotoxicity, and HT-2 was an inducer of the pre-hypertrophic state of the chondrocytes.

  • 1298.
    Zhang, Wei
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Chen, Jialin
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Backman, Ludvig J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Malm, Adam D.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Surface Topography and Mechanical Strain Promote Keratocyte Phenotype and Extracellular Matrix Formation in a Biomimetic 3D Corneal Model2017In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 6, no 5, article id UNSP 1601238Article in journal (Refereed)
    Abstract [en]

    The optimal functionality of the native corneal stroma is mainly dependent on the well-ordered arrangement of extracellular matrix (ECM) and the pressurized structure. In order to develop an in vitro corneal model, it is crucial to mimic the in vivo microenvironment of the cornea. In this study, the influence of surface topography and mechanical strain on keratocyte phenotype and ECM formation within a biomimetic 3D corneal model is studied. By modifying the surface topography of materials, it is found that patterned silk fibroin film with 600 grooves mm(-1) optimally supports cell alignment and ECM arrangement. Furthermore, treatment with 3% dome-shaped mechanical strain, which resembles the shape and mechanics of native cornea, significantly enhances the expression of keratocyte markers as compared to flat-shaped strain. Accordingly, a biomimetic 3D corneal model, in the form of a collagen-modified, silk fibroin-patterned construct subjected to 3% dome-shaped strain, is created. Compared to traditional 2D cultures, it supports a significantly higher expression of keratocyte and ECM markers, and in conclusion better maintains keratocyte phenotype, alignment, and fusiform cell shape. Therefore, the novel biomimetic 3D corneal model developed in this study serves as a useful in vitro 3D culture model to improve current 2D cultures for corneal studies.

  • 1299.
    Zhang, Wei
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). School of Medicine, Southeast University, Nanjing, China.
    Robertson, William Brett
    Zhao, Jinmin
    Chen, Weiwei
    Xu, Jiake
    Emerging Trend in the Pharmacotherapy of Osteoarthritis2019In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 10, article id 431Article, review/survey (Refereed)
    Abstract [en]

    Osteoarthritis (OA) is a degenerative joint disorder and one of the most prevalent diseases among the elderly population. Due to the limited spontaneous healing capacity of articular cartilage, it still remains challenging to find satisfactory treatment for OA. This review covers the emerging trends of pharmacologic therapies for OA such as traditional OA drugs (acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, serotonin-norepinephrine reuptake inhibitors (SNRIs), intra-articular injections of corticosteroids, and dietary supplements), which are effective in pain relief but not in reversing damage, and are frequently associated with adverse events. Alternatively, disease-modifying drugs provide promising alternatives for the management of OA. The development of these emerging OA therapeutic agents requires a comprehensive understanding of the pathophysiology of OA progression. The process of cartilage anabolism/catabolism, subchondral bone remodeling and synovial inflammation are identified as potential targets. These emerging OA drugs such as bone morphogenetic protein-7 (BMP-7), fibroblast growth factor-18 (FGF-18), human serum albumin (HSA), interleukin-1 (IL-1) inhibitor, h-Nerve growth factor (beta-NGF) antibody, matrix extracellular phosphoglycoprotein (MERE) and inverse agonist of retinoic acid-related orphan receptor alpha (ROR alpha) etc. have shown potential to modify progression of OA with minimal adverse effects. However, large-scale randomized controlled trials (RCTs) are needed to investigate the safety and efficacy before translation from bench to bedside.

  • 1300.
    Zhang, Yin-Ping
    et al.
    Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China.
    Wei, Huan-Huan
    Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China.
    Wang, Wen
    Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China.
    Xia, Ru-Yi
    Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China.
    Zhou, Xiao-Ling
    Department of Orthopaedics, the 1st Attached Hospital, Xi’an Jiaotong University, Xi'an, People’s Republic of China.
    Porr, Caroline
    School of Nursing, Memorial University, St. John’s, Canada.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Cross-cultural adaptation and validation of the osteoporosis assessment questionnaire short version (OPAQ-SV) for Chinese osteoporotic fracture females2016In: Clinical Rheumatology, ISSN 0770-3198, E-ISSN 1434-9949, Vol. 35, no 4, p. 1003-1010Article in journal (Refereed)
    Abstract [en]

    The Osteoporosis Assessment Questionnaire Short Version (OPAQ-SV) was cross-culturally adapted to measure health-related quality of life in Chinese osteoporotic fracture females and then validated in China for its psychometric properties. Cross-cultural adaptation, including translation of the original OPAQ-SV into Mandarin Chinese language, was performed according to published guidelines. Validation of the newly cross-culturally adapted OPAQ-SV was conducted by sampling 234 Chinese osteoporotic fracture females and also a control group of 235 Chinese osteoporotic females without fractures, producing robust content, construct, and discriminant validation results. Major categories of reliability were also met: the Cronbach alpha coefficient was 0.975, indicating good internal consistency; the test-retest reliability was 0.80; and principal component analysis resulted in a 6-factor structure explaining 75.847 % of the total variance. Further, the Comparative Fit Index result was 0.922 following the modified model confirmatory factor analysis, and the chi-squared test was 1.98. The root mean squared error of approximation was 0.078. Moreover, significant differences were revealed between females with fractures and those without fractures across all domains (p < 0.001). Overall, the newly cross-culturally adapted OPAQ-SV appears to possess adequate validity and reliability and may be utilized in clinical trials to assess the health-related quality of life in Chinese osteoporotic fracture females.

2324252627 1251 - 1300 of 1315
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf