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Publications (10 of 28) Show all publications
Persson, G., Johansson-Jänkänpää, E., Ganceviciene, R., Karadag, A. S., Bilgili, S. G., Omer, H. & Alexeyev, O. A. (2018). No evidence for follicular keratinocyte hyperproliferation in acne lesions as compared to autologous healthy hair follicles. Experimental dermatology, 27(6), 668-671
Open this publication in new window or tab >>No evidence for follicular keratinocyte hyperproliferation in acne lesions as compared to autologous healthy hair follicles
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2018 (English)In: Experimental dermatology, ISSN 0906-6705, E-ISSN 1600-0625, Vol. 27, no 6, p. 668-671Article in journal (Refereed) Published
Abstract [en]

Abnormal hyperkeratinization in sebaceous hair follicles has long been believed to play an important role in acne pathogenesis. Several early reports purported to provide histological evidence for hyperproliferation of keratinocytes in acne lesions by showing a higher expression of the Ki67 as well as certain keratins. The evidence is, however, not robust, and a number of methodological and technical limitations can be identified in these studies. In this study, we looked at the expression of proliferation, mitosis and apoptosis markers directly at acne skin lesions in 66 patients with acne vulgaris. Ki67 was assessed using immunohistochemistry and -tubulin, phospho-histone H3 and cleaved-PARP with immunofluorescence microscopy. Allogenic unaffected hair follicles from the same acne patients were used as an internal control. In both acne and control hair follicles, the -tubulin staining was universal, approaching 100% cells and showed no signs of changed assembly. Expression of cleaved-PARPthe apoptosis markerwas a rare event. Cell proliferation rate measured by the expression of Ki67 and phospho-histone H3 was virtually identical between acne and the two control groups. Our findings show the absence of increased keratinocyte proliferation in acne vulgaris. Alternative mechanisms are likely responsible for infundibular hyperkeratinization in acne pathogenesis.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018
Keywords
acne vulgaris, keratinocytes, Ki67, hyperproliferation
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:umu:diva-150877 (URN)10.1111/exd.13544 (DOI)000435937100011 ()29582469 (PubMedID)2-s2.0-85050213727 (Scopus ID)
Available from: 2018-08-31 Created: 2018-08-31 Last updated: 2018-08-31Bibliographically approved
Eklöf, V., Löfgren-Burström, A., Zingmark, C., Edin, S., Larsson, P., Karling, P., . . . Palmqvist, R. (2017). Cancer-associated fecal microbial markers in colorectal cancer detection. International Journal of Cancer, 141(12), 2528-2536
Open this publication in new window or tab >>Cancer-associated fecal microbial markers in colorectal cancer detection
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2017 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 141, no 12, p. 2528-2536Article in journal (Refereed) Published
Abstract [en]

Colorectal cancer (CRC) is the second most common cause of cancer death in the western world. An effective screening program leading to early detection of disease would severely reduce the mortality of CRC. Alterations in the gut microbiota have been linked to CRC, but the potential of microbial markers for use in CRC screening has been largely unstudied. We used a nested case-control study of 238 study subjects to explore the use of microbial markers for clbA+ bacteria harboring the pks pathogenicity island, afa-C+ diffusely adherent Escherichia coli harboring the afa-1 operon, and Fusobacterium nucleatum in stool as potential screening markers for CRC. We found that individual markers for clbA+ bacteria and F. nucleatum were more abundant in stool of patients with CRC, and could predict cancer with a relatively high specificity (81.5% and 76.9%, respectively) and with a sensitivity of 56.4% and 69.2%, respectively. In a combined test of clbA+ bacteria and F. nucleatum, CRC was detected with a specificity of 63.1% and a sensitivity of 84.6%. Our findings support a potential value of microbial factors in stool as putative noninvasive biomarkers for CRC detection. We propose that microbial markers may represent an important future screening strategy for CRC, selecting patients with a "high-risk" microbial pattern to other further diagnostic procedures such as colonoscopy.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
Keywords
F. nucleatum, clbA, colorectal cancer, gut microbiota, screening, stool
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-142380 (URN)10.1002/ijc.31011 (DOI)000413549900019 ()28833079 (PubMedID)
Available from: 2017-11-29 Created: 2017-11-29 Last updated: 2018-06-09Bibliographically approved
Alexeyev, O. A. (2017). Is it time to switch on or off the green light for ultraviolet-induced red fluorescence as a surrogate marker for Propionibacterium acnes in vivo?. Experimental dermatology, 26(1), 26-27
Open this publication in new window or tab >>Is it time to switch on or off the green light for ultraviolet-induced red fluorescence as a surrogate marker for Propionibacterium acnes in vivo?
2017 (English)In: Experimental dermatology, ISSN 0906-6705, E-ISSN 1600-0625, Vol. 26, no 1, p. 26-27Article in journal, Editorial material (Refereed) Published
Place, publisher, year, edition, pages
WILEY-BLACKWELL, 2017
Keywords
Propionibacterium acnes, acne vulgaris
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-132836 (URN)10.1111/exd.13126 (DOI)000393908000006 ()27307204 (PubMedID)
Available from: 2017-04-05 Created: 2017-04-05 Last updated: 2018-06-09Bibliographically approved
Omer, H., McDowell, A. & Alexeyev, O. A. (2017). Understanding the role of Propionibacterium acnes in acne vulgaris: The critical importance of skin sampling methodologies. Clinics in Dermatology, 35(2), 118-129
Open this publication in new window or tab >>Understanding the role of Propionibacterium acnes in acne vulgaris: The critical importance of skin sampling methodologies
2017 (English)In: Clinics in Dermatology, ISSN 0738-081X, E-ISSN 1879-1131, Vol. 35, no 2, p. 118-129Article in journal (Refereed) Published
Abstract [en]

Acne vulgaris is a chronic inflammatory skin condition classified by the Global Burden of Disease Study as the eighth most prevalent disease worldwide. The pathophysiology of the condition has been extensively studied, with an increase in sebum production, abnormal keratinization of the pilosebaceous follicle, and an inflammatory immune response all implicated in its etiology. One of the most disputed points, however, is the role of the gram:positive anaerobic bacterium Propionibacterium acnes in the development of acne, particularly when this organism is also found in normal sebaceous follicles of healthy skin. Against this background, we now describe the different sampling strategies that have been adopted for qualitative and quantitative study of P acnes within intact hair follicles of the skin and discuss the strengths and weaknesses of such methodologies for investigating the role of P acnes in the development of acne. 

National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:umu:diva-133811 (URN)10.1016/j.clindermatol.2016.10.003 (DOI)000397480100002 ()28274348 (PubMedID)
Available from: 2017-04-20 Created: 2017-04-20 Last updated: 2018-06-09Bibliographically approved
Eilers, H. & Alexeyev, O. A. (2016). Effect of GT-Peptide 10 and Triethyl Citrate on P. acnes Biofilm Formation, Viability, and Dispersion. Journal of drugs in dermatology, 15(6), 778-781
Open this publication in new window or tab >>Effect of GT-Peptide 10 and Triethyl Citrate on P. acnes Biofilm Formation, Viability, and Dispersion
2016 (English)In: Journal of drugs in dermatology, ISSN 1545-9616, Vol. 15, no 6, p. 778-781Article in journal (Refereed) Published
Abstract [en]

Background: P. acnes biofilms are emerging topics in acne vulgaris pathogenesis and may be responsible for antibiotic tolerance. Objective: To investigate the efficacy of GT peptide 10 either alone or in combination with triethyl citrate (TEC) in in vitro model of P acnes biofilm. Methods: Six-day-old P acnes biofilms were treated with various concentrations of these substances and biofilm dispersion and cell viability were monitored. Results: A 24-hour exposure of preformed biofilms to a combination of GT peptide 10/TEC led to killing of up to 92% of bacterial cells inside the biofilm. Neither the single substance nor the combination of both substances affected the biofilm integrity or resulted in biofilm dispersal. Conclusions: A combination of GT peptide 10/TEC shows antibacterial effects in in vitro model of P. acnes biofilm.

National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:umu:diva-129219 (URN)000387935700021 ()27272091 (PubMedID)
Available from: 2016-12-22 Created: 2016-12-21 Last updated: 2018-06-09Bibliographically approved
Jahns, A. C. & Alexeyev, O. A. (2016). Microbial colonization of normal skin: Direct visualization of 194 skin biopsies. Anaerobe, 38, 47-49
Open this publication in new window or tab >>Microbial colonization of normal skin: Direct visualization of 194 skin biopsies
2016 (English)In: Anaerobe, ISSN 1075-9964, E-ISSN 1095-8274, Vol. 38, p. 47-49Article in journal (Refereed) Published
Abstract [en]

Recent genetic studies have suggested the presence of numerous microbial species on and in the skin. We characterised microbial colonization of a large collection of skin biopsies from 194 healthy subjects by fluorescence assay. Forty per cent of all biopsies did not show any evidence for microbial colonization. Propionibacterium acnes was the sole predominant bacterial species in both sebaceous and non-sebaceous areas. Non- P. acnes species were present in approximately 30% of all colonized samples.. Only hair follicles and stratum corneum were colonized. Understanding of cutaneous microbiota requires validation from a variety of approaches and techniques.

Keywords
P. acnes, Skin, Immunofluorescence, Biopsy, Hair follicle
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:umu:diva-119261 (URN)10.1016/j.anaerobe.2015.11.011 (DOI)000372387600008 ()26655456 (PubMedID)
Available from: 2016-06-03 Created: 2016-04-15 Last updated: 2018-06-07Bibliographically approved
Jahns, A. C., Eilers, H. & Alexeyev, O. A. (2016). Transcriptomic analysis of Propionibacterium acnes biofilms in vitro. Anaerobe, 42, 111-118
Open this publication in new window or tab >>Transcriptomic analysis of Propionibacterium acnes biofilms in vitro
2016 (English)In: Anaerobe, ISSN 1075-9964, E-ISSN 1095-8274, Vol. 42, p. 111-118Article in journal (Refereed) Published
Abstract [en]

Propionibacterium acnes is a well-known commensal of the human skin connected to acne vulgaris and joint infections. It is extensively studied in planktonic cultures in the laboratory settings but occurs naturally in biofilms. In this study we have developed an in vitro biofilm model of P. acnes and studied growth features, matrix composition, matrix penetration by fluorescent-labeled antibiotics as well as gene expression. Antibiotic susceptibility of biofilms was studied and could be enhanced by increased glucose concentrations. Biofilm cells were characterized by up-regulated stress-induced genes and up regulation of genes coding for the potential virulence-associated CAMP factors. P. acnes can generate persister cells showing a reversible tolerance to 50 fold MIC of common antibiotics.

Keywords
Propionibacterium acnes, Biofilm, Persisters, RNA seq
National Category
Microbiology
Identifiers
urn:nbn:se:umu:diva-130465 (URN)10.1016/j.anaerobe.2016.10.001 (DOI)000390628600021 ()27725231 (PubMedID)
Available from: 2017-01-24 Created: 2017-01-20 Last updated: 2018-06-09Bibliographically approved
Jahns, A. C., Lundskog, B., Nosek, D., Killasli, H., Emtestam, L. & Alexeyev, O. A. (2015). Microbiology of folliculitis decalvans: a histological study of 37 patients [Letter to the editor]. Journal of the European Academy of Dermatology and Venereology, 29(5), 1025-1026
Open this publication in new window or tab >>Microbiology of folliculitis decalvans: a histological study of 37 patients
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2015 (English)In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 29, no 5, p. 1025-1026Article in journal, Letter (Other academic) Published
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:umu:diva-103187 (URN)10.1111/jdv.12448 (DOI)000353457100033 ()24629101 (PubMedID)
Available from: 2015-05-29 Created: 2015-05-18 Last updated: 2018-06-07Bibliographically approved
Jahns, A. C., Eilers, H., Ganceviciene, R. & Alexeyev, O. A. (2015). Propionibacterium species and follicular keratinocyte activation in acneic and normal skin. British Journal of Dermatology, 172(4), 981-987
Open this publication in new window or tab >>Propionibacterium species and follicular keratinocyte activation in acneic and normal skin
2015 (English)In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 172, no 4, p. 981-987Article in journal (Refereed) Published
Abstract [en]

Background The pathogenesis of acne vulgaris is multifactorial with increased sebum production, alteration in the quality of sebum lipids, dysregulation of the hormone microenvironment, follicular hyperkeratinization and Propionibacterium acnes-driven inflammation as major contributory factors. Hyperproliferation of keratinocytes is believed to contribute to hypercornification and eventually leads to comedone development. While the distribution of P. acnes is relatively well documented in acneic and healthy skin, little is known about P. granulosum and P. avidum.

Objectives To visualize directly the three major Propionibacterium in 117 control and 26 acneic skin samples. In addition, keratinocyte proliferation was evaluated.

Methods Propionibacteria were visualized by immunofluorescence microscopy, and keratinocyte proliferation was assessed by Ki67, keratin (K) 16 and p63 immunochemistry.

Results P. acnes was identified in 68 samples (48%), while P. granulosum was identified in 12 (8%) samples; P. avidum was not detected at all. Unexpectedly, acne samples did not show higher keratinocyte proliferation than controls, nor was there any association between bacterial colonization and expression of Ki67/K16/p63.

Conclusions Our findings do not support earlier notions of follicular keratinocyte hyperproliferation as a cause of ductal hypercornification in acneic facial skin. Further studies on the mechanisms underlying hypercornification in acne pathogenesis are needed.

National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:umu:diva-102356 (URN)10.1111/bjd.13436 (DOI)000351952100057 ()25279837 (PubMedID)
Available from: 2015-06-02 Created: 2015-04-23 Last updated: 2018-06-07Bibliographically approved
Witek, B., El Wakil, A., Nord, C., Ahlgren, U., Eriksson, M., Vernersson-Lindahl, E., . . . Palmer, R. H. (2015). Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic Hypogonadism. PLoS ONE, 10(5), Article ID e0123542.
Open this publication in new window or tab >>Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic Hypogonadism
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2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 5, article id e0123542Article in journal (Refereed) Published
Abstract [en]

Mice lacking ALK activity have previously been reported to exhibit subtle behavioral phenotypes. In this study of ALK of loss of function mice we present data supporting a role for ALK in hypogonadotropic hypogonadism in male mice. We observed lower level of serum testosterone at P40 in ALK knock-out males, accompanied by mild disorganization of seminiferous tubules exhibiting decreased numbers of GATA4 expressing cells. These observations highlight a role for ALK in testis function and are further supported by experiments in which chemical inhibition of ALK activity with the ALK TKI crizotinib was employed. Oral administration of crizotinib resulted in a decrease of serum testosterone levels in adult wild type male mice, which reverted to normal levels after cessation of treatment. Analysis of GnRH expression in neurons of the hypothalamus revealed a significant decrease in the number of GnRH positive neurons in ALK knock-out mice at P40 when compared with control littermates. Thus, ALK appears to be involved in hypogonadotropic hypogonadism by regulating the timing of pubertal onset and testis function at the upper levels of the hypothalamic-pituitary gonadal axis.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-106607 (URN)10.1371/journal.pone.0123542 (DOI)000356768100016 ()25955180 (PubMedID)
Available from: 2015-07-28 Created: 2015-07-24 Last updated: 2018-06-07Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0001-9944-4717

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