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  • 1.
    Ahmad, Sajjad
    et al.
    Institute of Basic Medical Science, Khyber Medical University, KP, Peshawar, Pakistan.
    Ahmed, Jawad
    Institute of Pathology and Diagnostic Medicine, Khyber Medical University, Peshawar, Pakistan.
    Khalifa, Eman H.
    Al Baha University Faculty of Applied Medical Sciences, Saudi Arabia.
    Khattak, Farhad Ali
    Research & development Cell, Khyber College of Dentistry (KCD), Peshawar, Pakistan.
    khan, Anwar Sheed
    Provincial TB Reference laboratory, Hayatabad Medical Complex, PK, Peshawar, Pakistan.
    Farooq, Syed Umar
    Department of oral pathology, Khyber College of Dentistry, Peshawar, Pakistan.
    Osman, Sannaa M.A.
    Alzaiem Alazhari University Faculty of Medicine, Sudan.
    Salih, Magdi M.
    Taif University College of Science, Saudi Arabia.
    Ullah, Nadeem
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Khan, Taj Ali
    Institute of Pathology and Diagnostic Medicine, Khyber Medical University, Peshawar, Pakistan; Division of Infectious Diseases & Global Medicine,Department of Medicine, University of Florida, FL, Gainesville, United States.
    Novel mutations in genes of the IL-12/IFN-γ axis cause susceptibility to tuberculosis2023Ingår i: Journal of Infection and Public Health, ISSN 1876-0341, E-ISSN 1876-035X, Vol. 16, nr 9, s. 1368-1378Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The IL-12/23/ISG15-IFN-γ pathway is the main immunological pathway for controlling intra-macrophagic microorganisms such as Mycobacteria, Salmonella, and Leishmania spp. Consequently, upon mutations in genes of the IL-12/23/ISG15-IFN-γ pathway cause increased susceptibility to intra-macrophagic pathogens, particularly to Mycobacteria. Therefore, the purpose of this study was to characterize the mutations in genes of the IL-12/23/ISG15-IFN-γ pathway in severe tuberculosis (TB) patients.

    Methods: Clinically suspected TB was initially confirmed in four patients (P) (P1, P2, P3, and P4) using the GeneXpert MTB/RIF and culturing techniques. The patients' Peripheral blood mononuclear cells (PBMCs) were then subjected to ELISA to measure Interleukin 12 (IL-12) and interferon gamma (IFN-γ). Flow cytometry was used to detect the surface expressions of IFN-γR1 and IFN-γR2 as well as IL-12Rβ1and IL-12Rβ2 on monocytes and T lymphocytes, respectively.The phosphorylation of signal transducer and activator of transcription 1(STAT1) on monocytes and STAT4 on T lymphocytes were also detected by flow cytometry. Sanger sequencing was used to identify mutations in the IL-12Rβ1, STAT1, NEMO, and CYBB genes.

    Results: P1's PBMCs exhibited reduced IFN-γ production, while P2's and P3's PBMCs exhibited impaired IL-12 induction. Low IL-12Rβ1 surface expression and reduced STAT4 phosphorylation were demonstrated by P1's T lymphocytes, while impaired STAT1 phosphorylation was detected in P2's monocytes. The impaired IκB-α degradation and abolished H2O2 production in monocytes and neutrophils of P3 and P4 were observed, respectively. Sanger sequencing revealed novel nonsense homozygous mutation: c.191 G>A/p.W64 * in exon 3 of the IL-12Rβ1 gene in P1, novel missense homozygous mutation: c.107 A>T/p.Q36L in exon 3 of the STAT1 gene in P2, missense hemizygous mutation:: c.950 A>C/p.Q317P in exon 8 of the NEMO gene in P3, and nonsense hemizygous mutation: c.868 C>T/p.R290X in exon 8 of CYBB gene in P4.

    Conclusion: Our findings broaden the clinical and genetic spectra associated with IL-12/23/ISG15-IFN-γ axis anomalies. Additionally, our data suggest that TB patients in Pakistan should be investigated for potential genetic defects due to high prevalence of parental consanguinity and increased incidence of TB in the country.

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  • 2.
    Muhammad, Khayal
    et al.
    Department of Clinical Pharmacy, Faculty of Pharmacy Near East University, Nicosia, North Cyprus, Turkey; Faculty of Pharmaceutical Sciences, Abasyn University, Peshawar, KPK, Pakistan.
    Shah, Syed Sikandar
    Department of Clinical Pharmacy, Faculty of Pharmacy, European University of Lefke, Lefke, Northern Cyprus, TR-10 Mersin, Turkey.
    Muhammad, Gul
    Department of Medicine, DHQ Teaching Hospital, D.I.Khan, KPK, Pakistan.
    Ullah, Nadeem
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Butt, Muhammad Hammad
    Faculty of Pharmacy, University of Central Punjab, Lahore, Punjab, Pakistan.
    Higazi, Hassan
    Department of Medical Laboratory Sciences, College of Health Sciences, Gulf Medical University, Ajman, United Arab Emirates.
    Baraka, Mohamed A.
    Clinical Pharmacy Program, College of Pharmacy, Al-Ain University, Al-Ain Campus, United Arab Emirates; Clinical Pharmacy Department, College of Pharmacy, Al-Azhar University, Cairo, Egypt.
    Physicians' perception about the side effects of covid-19 vaccine and their role in vaccination program2022Ingår i: Disaster Medicine and Public Health Preparedness, ISSN 1935-7893, E-ISSN 1938-744X, Vol. 16, nr 6, s. 2290-2292Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: The Coronavirus disease 2019 (COVID-19) caused many problems in the health sector. Effective and safe vaccines are the only tool to combat the COVID-19 disease. Researchers and regulatory agencies have made efforts to develop such vaccines and healthcare professionals were prioritized for the vaccination program as first-line care providers. Considering this prioritization, we aimed to assess the physicians' perceptions regarding the side effects of the COVID-19 vaccine.

    Methods: An interview-based study was conducted from May 5 May to November 5, 2021 (6 months) in a teaching hospital in the capital city of Islamabad, Pakistan.

    Results: Among the 200 physicians who agreed to participate in the interview, 74% were male. A total of 94% did not experience any side effects after receiving the COVID-19 vaccine, regardless of the type of vaccine; 6% experienced side effects. Furthermore, 90% of physicians were afraid of side effects due to the high number of vaccine doses.

    Conclusion: Conclusively, physicians had a positive perception regarding the COVID-19 vaccine. Healthcare authorities and related departments must take precautions to ensure the effective and safe COVID-19 vaccine to change the perceptions of physicians who had a negative perception. This will not only reduce the reluctance among physicians regarding administering COVID-19 vaccine, but will also boost and facilitate the vaccination program for the general public as well.

  • 3.
    Muhammad, Noor
    et al.
    Department of Microbiology, Kohat University of Science and Technology, Kohat, Pakistan.
    Khan, Muhammad Tahir
    Zhongjing Research and Industrialization, Institute of Chinese Medicine, Zhongguancun Scientific Park, Meixi, Nanyang, China; Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, KM Defense Road, Lahore, Pakistan.
    Ali, Sajid
    Department of Microbiology & Biotechnology, Bacha Khan University, Charsadda, Pakistan.
    Khan, Taj Ali
    Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan.
    Khan, Anwar Sheed
    Department of Microbiology, Kohat University of Science and Technology, Kohat, Pakistan.
    Ullah, Nadeem
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Higazi, Hassan
    Department of Medical Laboratory Sciences, College of Health Sciences, Gulf Medical University, Ajman P.O. Box 4184, United Arab Emirates.
    Ali, Sara
    Department of Medical Laboratory Sciences, College of Health Sciences, Gulf Medical University, Ajman P.O. Box 4184, United Arab Emirates.
    Mohamed, Salma
    Department of Medical Laboratory Sciences, College of Health Sciences, Gulf Medical University, Ajman P.O. Box 4184, United Arab Emirates.
    Qasim, Muhammad
    Department of Microbiology, Kohat University of Science and Technology, Kohat, Pakistan.
    Novel mutations in MPT64 secretory protein of Mycobacterium tuberculosis complex2023Ingår i: International Journal of Environmental Research and Public Health, ISSN 1661-7827, E-ISSN 1660-4601, Vol. 20, nr 3, artikel-id 2530Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Tuberculosis (TB) is a global health problem caused by the Mycobacterium tuberculosis complex (MTBC). These bacteria secrete various proteins involved in the pathogenesis and persistence of MTBC. Among the secretory proteins, MPT64 (Rv1980C) is highly conserved and is also known as a major culture filtrate that is used in rapid diagnosis of MTBC. In the current study, we aimed to find the mutation in this highly conserved protein in isolates from the Pashtun-dominant province of Pakistan. We analyzed 470 M. tuberculosis whole-genome sequences of Khyber Pakhtunkhwa Province. Mutations in the MPT64 gene were screened through TB-Profiler and BioEdit software tools. The DynaMut web server was used to analyze the impact of the mutation on protein dynamics and stability. Among 470 MTB genomes, three non-synonymous mutations were detected in nine isolates, and one synonymous mutation (G208A) was found in four isolates. Mutation G211T (F159L), which was detected at the C-terminal domain of the protein in six isolates, was the most prominent. The second novel mutation, T480C (I70V), was detected in two isolates at the C-terminal side of the protein structure. The third novel mutation, A491C (L66R), was detected in a single isolate at the N-terminal side of the MPT64 protein. The effect of these three mutations was destabilizing on the protein structure. The molecular flexibility of the first two mutations increased, and the last one decreased. MPT64 is a highly conserved secretory protein, harboring only a few mutations. This study provides useful information for better managing the diagnosis of MTB isolates in high TB-burden countries.

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