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Article ; Online: Emerging Role of the IL-36/IL-36R Axis in Multiple Inflammatory Skin Diseases.

Ahmad, Fareed / Alam, Majid Ali / Ansari, Abdul Wahid / Jochebeth, Anh / Leo, Rari / Al-Abdulla, Mohammed Nasser / Al-Khawaga, Sara / AlHammadi, Ayda / Al-Malki, Aysha / Al Naama, Khalifa / Ahmad, Aamir / Buddenkotte, Jörg / Steinhoff, Martin

The Journal of investigative dermatology

2024 Volume 144, Issue 2, Page(s) 206–224

Abstract: IL-36 is a most recent member of the IL-1 cytokine family, primarily expressed at barrier sites of the body such as the skin, lungs, and intestine. It plays a vital role in inflammation and is implicated in the development of various cutaneous; ... ...

Abstract	IL-36 is a most recent member of the IL-1 cytokine family, primarily expressed at barrier sites of the body such as the skin, lungs, and intestine. It plays a vital role in inflammation and is implicated in the development of various cutaneous; intestinal; and pulmonary disorders, including psoriasis, inflammatory bowel disease, and chronic obstructive pulmonary disease. IL-36 comprises 4 isoforms: the proinflammatory IL-36α, IL-36β, and IL-36γ and the anti-inflammatory IL-36R antagonist. An imbalance between proinflammatory and anti-inflammatory IL-36 isoforms can contribute to the inflammatory fate of cells and tissues. IL-36 cytokines signal through an IL-36R heterodimer mediating their function through canonical signaling cacade, including the NF-B pathway. Prominent for its role in psoriasis, IL-36 has recently been associated with disease mechanisms in atopic dermatitis, hidradenitis suppurativa, neutrophilic dermatoses, autoimmune blistering disease, and Netherton syndrome. The major cutaneous source of IL-36 cytokines is keratinocytes, pointing to its role in the communication between the epidermis, innate (neutrophils, dendritic cells) immune system, and adaptive (T helper [Th]1 cells, Th17) immune system. Thus, cutaneous IL-36 signaling is crucial for the immunopathological outcome of various skin diseases. Consequently, the IL-36/IL-36R axis has recently been recognized as a promising drug target for the treatment of inflammatory disorders beyond psoriasis. This review summarizes the current update on IL-36 cytokines in inflammatory skin diseases.
MeSH term(s)	Humans ; Anti-Inflammatory Agents ; Cytokines/metabolism ; Dermatitis ; Interleukin-1/metabolism ; Protein Isoforms ; Psoriasis ; Skin Diseases/drug therapy ; Skin Diseases/metabolism ; Receptors, Interleukin-1/metabolism
Chemical Substances	Anti-Inflammatory Agents ; Cytokines ; Interleukin-1 ; Protein Isoforms ; IL36A protein, human ; IL36B protein, human ; IL36RN protein, human ; Receptors, Interleukin-1
Language	English
Publishing date	2024-01-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2023.11.004
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Article ; Online: Azithromycin downregulates ICOS (CD278) and OX40 (CD134) expression and mTOR activity of TCR-activated T cells to inhibit proliferation.

Ansari, Abdul Wahid / Ahmad, Fareed / Raheed, Thesni / Jochebeth, Anh / Mateo, Jericha Miles Pamiloza / Abdulrahman, Nabeel / Joy, Elizabeth Febu / Alam, Majid Ali / Buddenkotte, Joerg / Hamoudi, Rifat Akram / Steinhoff, Martin

International immunopharmacology

2023 Volume 124, Issue Pt A, Page(s) 110831

Abstract: The precise mechanism of macrolide antibiotic azithromycin (AZM) mediated CD4+ T cell suppression is not fully understood. Given the crucial role of co-stimulatory signaling in T-lymphocyte function, we tested in vitro effects of AZM on two of the most ... ...

Abstract	The precise mechanism of macrolide antibiotic azithromycin (AZM) mediated CD4+ T cell suppression is not fully understood. Given the crucial role of co-stimulatory signaling in T-lymphocyte function, we tested in vitro effects of AZM on two of the most extensively investigated costimulatory molecules, ICOS and OX40 in context to CD4+ T cell proliferation. Using multi-color flow cytometry approach on TCR-activated healthy donor peripheral blood mononuclear cells, we observed a marked reduction in the frequencies and surface expression of ICOS and OX40 receptors following AZM treatment. Functionally, in contrast to ICOS- and OX40- CD3+ CD4+ T cells, AZM treated ICOS+ and OX40+ displayed profound reduction in cell proliferation. Furthermore, AZM treated T cells displaying reduced levels of ICOS and OX40 found to be associated with suppressed mTOR activity as detected by phosphorylation levels of S6 ribosomal protein. This study provides new insights on potential mechanism of AZM mediated inhibition of T cell proliferation by targeting costimulatory pathways.
Language	English
Publishing date	2023-08-24
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2043785-7
ISSN	1878-1705 ; 1567-5769
ISSN (online)	1878-1705
ISSN	1567-5769
DOI	10.1016/j.intimp.2023.110831
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Article ; Online: Reported Male Circumcision Practices in a Muslim-Majority Setting.

Anwer, Abdul Wahid / Samad, Lubna / Iftikhar, Sundus / Baig-Ansari, Naila

BioMed research international

2017 Volume 2017, Page(s) 4957348

Abstract: ... ...

Abstract	Introduction
MeSH term(s)	Adolescent ; Adult ; Child ; Child, Preschool ; Circumcision, Male ; Female ; Humans ; Infant ; Islam ; Male
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article
ZDB-ID	2698540-8
ISSN	2314-6141 ; 2314-6133
ISSN (online)	2314-6141
ISSN	2314-6133
DOI	10.1155/2017/4957348
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Article ; Online: Epigenetic regulation of CXCR4 signaling in cancer pathogenesis and progression.

Alsayed, Reem Khaled M E / Khan, Abdul Q / Ahmad, Fareed / Ansari, Abdul Wahid / Alam, Majid Ali / Buddenkotte, Jorg / Steinhoff, Martin / Uddin, Shahab / Ahmad, Aamir

Seminars in cancer biology

2022 Volume 86, Issue Pt 2, Page(s) 697–708

Abstract: Signaling involving chemokine receptor CXCR4 and its ligand SDF-1/CXL12 has been investigated for many years for its possible role in cancer progression and pathogenesis. Evidence emerging from clinical studies in recent years has further established ... ...

Abstract	Signaling involving chemokine receptor CXCR4 and its ligand SDF-1/CXL12 has been investigated for many years for its possible role in cancer progression and pathogenesis. Evidence emerging from clinical studies in recent years has further established diagnostic as well as prognostic importance of CXCR4 signaling. CXCR4 and SDF-1 are routinely reported to be elevated in tumors, distant metastases, which correlates with poor survival of patients. These findings have kindled interest in the mechanisms that regulate CXCR4/SDF-1 expression. Of note, there is a particular interest in the epigenetic regulation of CXCR4 signaling that may be responsible for upregulated CXCR4 in primary as well as metastatic cancers. This review first lists the clinical evidence supporting CXCR4 signaling as putative cancer diagnostic and/or prognostic biomarker, followed by a discussion on reported epigenetic mechanisms that affect CXCR4 expression. These mechanisms include regulation by non-coding RNAs, such as, microRNAs, long non-coding RNAs and circular RNAs. Additionally, we also discuss the regulation of CXCR4 expression through methylation and acetylation. Better understanding and appreciation of epigenetic regulation of CXCR4 signaling can invariably lead to identification of novel therapeutic targets as well as therapies to regulate this oncogenic signaling.
MeSH term(s)	Humans ; Epigenesis, Genetic ; Chemokine CXCL12/genetics ; Receptors, CXCR4/genetics ; Neoplasms/genetics ; Signal Transduction/genetics ; Prognosis ; MicroRNAs/genetics
Chemical Substances	Chemokine CXCL12 ; Receptors, CXCR4 ; MicroRNAs ; CXCR4 protein, human
Language	English
Publishing date	2022-03-26
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1033980-2
ISSN	1096-3650 ; 1044-579X
ISSN (online)	1096-3650
ISSN	1044-579X
DOI	10.1016/j.semcancer.2022.03.019
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Article ; Online: Optimizing sowing date for peanut genotypes in arid and semi-arid subtropical regions.

Ijaz, Muhammad / Nawaz, Ahmad / Ul-Allah, Sami / Sher, Ahmad / Sattar, Abdul / Sarwar, Muhammad / Hussain, Ijaz / Ur Rehman, Anees / Wahid, Muhammad Ashfaq / Ansari, Mohammad Javed / Hessini, Kamel

publication RETRACTED

PloS one

2021 Volume 16, Issue 6, Page(s) e0252393

Abstract: Peanut (Arachis hypogea L.) is an important nut crop extensively grown in rainfed regions of Pakistan. The crop requires low inputs; thus, could grow successfully under diverse environmental conditions. Due to pegging ability, peanut grows aggressively ... ...

Abstract	Peanut (Arachis hypogea L.) is an important nut crop extensively grown in rainfed regions of Pakistan. The crop requires low inputs; thus, could grow successfully under diverse environmental conditions. Due to pegging ability, peanut grows aggressively in sandy and sandy-loam soils. However, it has not introduced to Thal region of southern Punjab, Pakistan. A two-year field experiment was conducted to optimize sowing dates for two peanut genotypes ('BARI-2016' and 'NO-334') in Thal region (Layyah). Similarly, a yield trial was conducted at Chakwal where both genotypes are extensively grown. Five sowing dates (10th April, 1st May, 20th May, 10th June and 30th June) were included in the study. The highest seed yield was obtained with early sown crop (10th April) during both years. Pod formation reduced with increasing atmospheric temperature and no pods were formed on the plants sown on 30th June. Decreased pod formation seemed a major reason for low yield in late-sown crop. The highest yield was observed for the crop sown on 10th April, which was decreased by 40% for the crop sown on 1st May. Genotype 'BARI-2016' performed better for seed yield at both locations compared with 'NO-334'. The results suggested that genotype 'BARI-2016' is more adaptive to arid and semi-arid condition under rainfed or irrigated conditions. Sowing peanut at optimum time would increase seed yield in arid and semi-arid regions. Nonetheless, 'BARI-2016' can be grown under rainfed and irrigated conditions successfully.
MeSH term(s)	Agriculture/methods ; Arachis/genetics ; Arachis/growth & development ; Droughts ; Genotype ; Tropical Climate
Language	English
Publishing date	2021-06-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Retracted Publication
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0252393
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Article ; Online: Interleukin-17, a salivary biomarker for COVID-19 severity.

Sharif-Askari, Fatemeh Saheb / Sharif-Askari, Narjes Saheb / Hafezi, Shirin / Mdkhana, Bushra / Alsayed, Hawra Ali Hussain / Ansari, Abdul Wahid / Mahboub, Bassam / Zakeri, Adel M / Temsah, Mohamad-Hani / Zahir, Walid / Hamid, Qutayba / Halwani, Rabih

PloS one

2022 Volume 17, Issue 9, Page(s) e0274841

Abstract: Objectives: T-helper 17 cell-mediated response and their effector IL-17 cytokine induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a major cause of COVID-19 disease severity and death. Therefore, the study aimed to ... ...

Abstract	Objectives: T-helper 17 cell-mediated response and their effector IL-17 cytokine induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a major cause of COVID-19 disease severity and death. Therefore, the study aimed to determine if IL-17 level in saliva mirrors its circulatory level and hence can be used as a non-invasive biomarker for disease severity. Methods: Interleukin-17 (IL-17) level was evaluated by ELISA in saliva and blood of 201 adult COVID-19 patients with different levels of severity. The IL-17 saliva level was also associated with COVID-19 disease severity, and need for mechanical ventilation and/or death within 29 days after admission of severe COVID-19 patients. Results: We found that IL-17 level in saliva of COVID-19 patients reflected its circulatory level. High IL-17 level in saliva was associated with COVID-19 severity (P<0.001), need for mechanical ventilation (P = 0.002), and/or death by 29 days (P = 0.002), after adjusting for patients' demographics, comorbidity, and COVID-19 serum severity markers such as D-Dimer, C-reactive protein, and ferritin. Conclusion: We propose that saliva IL-17 level could be used as a biomarker to identify patients at risk of developing severe COVID-19.
MeSH term(s)	Adult ; Biomarkers ; C-Reactive Protein ; COVID-19/diagnosis ; Cytokines ; Ferritins ; Humans ; Interleukin-17 ; SARS-CoV-2
Chemical Substances	Biomarkers ; Cytokines ; Interleukin-17 ; C-Reactive Protein (9007-41-4) ; Ferritins (9007-73-2)
Language	English
Publishing date	2022-09-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0274841
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Article ; Online: Upregulation of interleukin-19 in saliva of patients with COVID-19.

Saheb Sharif-Askari, Fatemeh / Saheb Sharif-Askari, Narjes / Hafezi, Shirin / Goel, Swati / Ali Hussain Alsayed, Hawra / Ansari, Abdul Wahid / Mahboub, Bassam / Al-Muhsen, Saleh / Temsah, Mohamad-Hani / Hamid, Qutayba / Halwani, Rabih

Scientific reports

2022 Volume 12, Issue 1, Page(s) 16019

Abstract: Cytokines are major players in orchestrating inflammation, disease pathogenesis and severity during COVID-19 disease. However, the role of IL-19 in COVID-19 pathogenesis remains elusive. Herein, through the analysis of transcriptomic datasets of SARS-CoV- ...

Abstract	Cytokines are major players in orchestrating inflammation, disease pathogenesis and severity during COVID-19 disease. However, the role of IL-19 in COVID-19 pathogenesis remains elusive. Herein, through the analysis of transcriptomic datasets of SARS-CoV-2 infected lung cells, nasopharyngeal swabs, and lung autopsies of COVID-19 patients, we report that expression levels of IL-19 and its receptor, IL-20R2, were upregulated following SARS-CoV-2 infection. Of 202 adult COVID-19 patients, IL-19 protein level was significantly higher in blood and saliva of asymptomatic patients compared to healthy controls when adjusted for patients' demographics (P < 0.001). Interestingly, high saliva IL-19 level was also associated with COVID-19 severity (P < 0.0001), need for mechanical ventilation (P = 0.002), and/or death (P = 0.010) within 29 days of admission, after adjusting for patients' demographics, diabetes mellitus comorbidity, and COVID-19 serum markers of severity such as D-dimer, C-reactive protein, and ferritin. Moreover, patients who received interferon beta during their hospital stay had lower plasma IL-19 concentrations (24 pg mL
MeSH term(s)	Adult ; Biomarkers ; C-Reactive Protein ; COVID-19 ; Cytokines ; Ferritins ; Humans ; Interferon-beta ; Interleukins/genetics ; SARS-CoV-2 ; Saliva ; Up-Regulation
Chemical Substances	Biomarkers ; Cytokines ; IL19 protein, human ; Interleukins ; Interferon-beta (77238-31-4) ; C-Reactive Protein (9007-41-4) ; Ferritins (9007-73-2)
Language	English
Publishing date	2022-09-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-20087-w
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Article ; Online: Combined application of zinc and silicon alleviates terminal drought stress in wheat by triggering morpho-physiological and antioxidants defense mechanisms.

Sattar, Abdul / Wang, Xiukang / Abbas, Tahira / Sher, Ahmad / Ijaz, Muhammad / Ul-Allah, Sami / Irfan, Muhammad / Butt, Madiha / Wahid, Muhammad Ashfaq / Cheema, Mumtaz / Fiaz, Sajid / Qayyum, Abdul / Ansari, Mohammad Javed / Alharbi, Sulaiman Ali / Wainwright, Milton / Ahmad, Furqan / Xie, Kui / Zuan, Ali Tan Kee

publication RETRACTED

PloS one

2021 Volume 16, Issue 10, Page(s) e0256984

Abstract: Wheat is an important global staple food crop; however, its productivity is severely hampered by changing climate. Erratic rain patterns cause terminal drought stress, which affect reproductive development and crop yield. This study investigates the ... ...

Abstract	Wheat is an important global staple food crop; however, its productivity is severely hampered by changing climate. Erratic rain patterns cause terminal drought stress, which affect reproductive development and crop yield. This study investigates the potential and zinc (Zn) and silicon (Si) to ameliorate terminal drought stress in wheat and associated mechanisms. Two different drought stress levels, i.e., control [80% water holding capacity (WHC) was maintained] and terminal drought stress (40% WHC maintained from BBCH growth stage 49 to 83) combined with five foliar-applied Zn-Si combinations (i.e., control, water spray, 4 mM Zn, 40 mM Si, 4 mM Zn + 40 mM Si applied 7 days after the initiation of drought stress). Results revealed that application of Zn and Si improved chlorophyll and relative water contents under well-watered conditions and terminal drought stress. Foliar application of Si and Zn had significant effect on antioxidant defense mechanism, proline and soluble protein, which showed that application of Si and Zn ameliorated the effects of terminal drought stress mainly by regulating antioxidant defense mechanism, and production of proline and soluble proteins. Combined application of Zn and Si resulted in the highest improvement in growth and antioxidant defense. The application of Zn and Si improved yield and related traits, both under well-watered conditions and terminal drought stress. The highest yield and related traits were recorded for combined application of Zn and Si. For grain and biological yield differences among sole and combined Zn-Si application were statistically non-significant (p>0.05). In conclusion, combined application of Zn-Si ameliorated the adverse effects of terminal drought stress by improving yield through regulating antioxidant mechanism and production of proline and soluble proteins. Results provide valuable insights for further cross talk between Zn-Si regulatory pathways to enhance grain biofortification.
MeSH term(s)	Antioxidants/metabolism ; Chlorophyll/metabolism ; Droughts ; Silicon/administration & dosage ; Silicon/metabolism ; Stress, Physiological ; Triticum/physiology ; Water/metabolism ; Zinc/administration & dosage ; Zinc/metabolism
Chemical Substances	Antioxidants ; Water (059QF0KO0R) ; Chlorophyll (1406-65-1) ; Zinc (J41CSQ7QDS) ; Silicon (Z4152N8IUI)
Language	English
Publishing date	2021-10-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Retracted Publication
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0256984
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Article ; Online: Reported Male Circumcision Practices in a Muslim-Majority Setting

Abdul Wahid Anwer / Lubna Samad / Sundus Iftikhar / Naila Baig-Ansari

BioMed Research International, Vol

2017 Volume 2017

Abstract: Introduction. Male circumcision is a recommended practice in Muslim tradition. It is important to ensure that this procedure is performed as safely as possible in these communities. Methods. Five hundred adult men and women with at least one male child ... ...

Abstract	Introduction. Male circumcision is a recommended practice in Muslim tradition. It is important to ensure that this procedure is performed as safely as possible in these communities. Methods. Five hundred adult men and women with at least one male child less than 18 years were interviewed in Karachi, Pakistan, regarding details of their child’s circumcision. The survey focused on actual and perceived delays in circumcision and perceptions about appropriate age and reasons and benefits and complications of the procedure. Circumcisions done after two months of age were defined as delayed. Results. Religious requirement was the primary reason for circumcision in 92.6% of children. However, 89.6% of respondents were of the opinion that circumcision had medical benefits as well. Half of the children (54.1%) had delayed circumcision (range 2.5 months to 13 years), even though 81.2% of parents were of the opinion that circumcisions should be done within 60 days of birth. Facility-delivered babies had less delay in circumcisions (49.1%) as compared to home-delivered babies (60.5%). Conclusion. Understanding the perceptions and practices around male circumcision can help guide national strategies for designing and implementing safe circumcision programs in Muslim-majority settings, with the potential to benefit an annual birth cohort of 20–25 million boys worldwide.
Keywords	Medicine ; R
Subject code	360
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
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Article: Upregulation of interleukin-19 in severe asthma: a potential saliva biomarker for asthma severity.

Saheb Sharif-Askari, Fatemeh / Saheb Sharif-Askari, Narjes / Goel, Swati / Mahboub, Bassam / Ansari, Abdul Wahid / Temsah, Mohamad-Hani / Zakri, Adel M / Ratemi, Elaref / Hamoudi, Rifat / Hamid, Qutayba / Halwani, Rabih

ERJ open research

2021 Volume 7, Issue 3

Abstract: Interleukin (IL)-19, a designated IL-20 subfamily cytokine, has been implicated in inflammatory disorders including rheumatoid arthritis, psoriasis and, lately, asthma. Here, through the analysis of transcriptomic datasets of lung tissue of large asthma ... ...

Abstract	Interleukin (IL)-19, a designated IL-20 subfamily cytokine, has been implicated in inflammatory disorders including rheumatoid arthritis, psoriasis and, lately, asthma. Here, through the analysis of transcriptomic datasets of lung tissue of large asthma cohorts, we report that IL-19 expression is upregulated in asthma and correlates with disease severity. The gene expression of IL-19 was significantly higher in lung tissue from patients with severe and mild/moderate asthma compared to healthy controls. IL-19 protein level, however, was significantly higher in the blood and saliva of patients with severe asthma compared to mild/moderate subgroups as measured by ELISA assay. IL-19 protein level was not affected by corticosteroid treatment in plasma. Our data provide insights into the potential use of IL-19 as a saliva marker for asthma severity and a potential therapeutic target.
Language	English
Publishing date	2021-07-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2827830-6
ISSN	2312-0541
ISSN	2312-0541
DOI	10.1183/23120541.00984-2020
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