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Article ; Online: Virus-induced diabetes mellitus, revisiting infection etiology in light of SARS-CoV-2.

Jeremiah, Sundararaj Stanleyraj / Moin, Abu Saleh Md / Butler, Alexandra E

2024 , Page(s) 155917

Abstract: Diabetes mellitus (DM) is comprised of two predominant subtypes: type 1 diabetes mellitus (T1DM), accounting for approximately 5 % of cases worldwide and resulting from autoimmune destruction of insulin-producing β-cells, and type 2 (T2DM), accounting ... ...

Abstract	Diabetes mellitus (DM) is comprised of two predominant subtypes: type 1 diabetes mellitus (T1DM), accounting for approximately 5 % of cases worldwide and resulting from autoimmune destruction of insulin-producing β-cells, and type 2 (T2DM), accounting for approximately 95 % of cases globally and characterized by the inability of pancreatic β-cells to meet the demand for insulin due to a relative β-cell deficit in the setting of peripheral insulin resistance. Both types of DM involve derangement of glucose metabolism and are metabolic diseases generally considered to be initiated by a combination of genetic and environmental factors. Viruses have been reported to play a role as infectious etiological factors in the initiation of both types of DM in predisposed individuals. Among the reported viral infections causing DM in humans, the most studied include coxsackie B virus, cytomegalovirus and hepatitis C virus. The recent COVID-19 pandemic has highlighted the diabetogenic potential of SARS-CoV-2, rekindling interest in the field of virus-induced diabetes (VID). This review discusses the reported mechanisms of viral-induced DM, addressing emerging concepts in VID, as well as highlighting areas where knowledge is lacking, and further investigation is warranted.
Language	English
Publishing date	2024-04-18
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	80230-x
ISSN	1532-8600 ; 0026-0495
ISSN (online)	1532-8600
ISSN	0026-0495
DOI	10.1016/j.metabol.2024.155917
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Article ; Online: A Cross-Sectional Study of Alzheimer-Related Proteins in Women with Polycystic Ovary Syndrome.

Butler, Alexandra E / Moin, Abu Saleh Md / Sathyapalan, Thozhukat / Atkin, Stephen L

International journal of molecular sciences

2024 Volume 25, Issue 2

Abstract: Polycystic ovary syndrome (PCOS) is the most common endocrine condition in women of reproductive age, and several risk factors found in PCOS are associated with an increased risk of Alzheimer's disease (AD). Proteins increased in AD have been reported to ...

Abstract	Polycystic ovary syndrome (PCOS) is the most common endocrine condition in women of reproductive age, and several risk factors found in PCOS are associated with an increased risk of Alzheimer's disease (AD). Proteins increased in AD have been reported to include fibronectin (FN) fragments 3 and 4 (FN1.3 and FN1.4, respectively) and ApoE. We hypothesized that Alzheimer-related proteins would be dysregulated in PCOS because of associated insulin resistance and obesity. In this comparative cross-sectional analysis, aptamer-based SomaScan proteomic analysis for the detection of plasma Alzheimer-related proteins was undertaken in a PCOS biobank of 143 women with PCOS and 97 control women. Amyloid precursor protein (APP) (
MeSH term(s)	Humans ; Female ; Cross-Sectional Studies ; Polycystic Ovary Syndrome ; Alzheimer Disease ; Diabetes Mellitus, Type 2 ; Prospective Studies ; Proteomics ; Apolipoproteins E ; Amyloid beta-Protein Precursor ; Apolipoprotein E3
Chemical Substances	Apolipoproteins E ; Amyloid beta-Protein Precursor ; Apolipoprotein E3
Language	English
Publishing date	2024-01-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25021158
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Article ; Online: A Cross-Sectional Study of Protein Changes Associated with Dementia in Non-Obese Weight Matched Women with and without Polycystic Ovary Syndrome.

Butler, Alexandra E / Moin, Abu Saleh Md / Sathyapalan, Thozhukat / Atkin, Stephen L

International journal of molecular sciences

2024 Volume 25, Issue 4

Abstract: Dysregulated Alzheimer's disease (AD)-associated protein expression is reported in polycystic ovary syndrome (PCOS), paralleling the expression reported in type 2 diabetes (T2D). We hypothesized, however, that these proteins would not differ between ... ...

Abstract	Dysregulated Alzheimer's disease (AD)-associated protein expression is reported in polycystic ovary syndrome (PCOS), paralleling the expression reported in type 2 diabetes (T2D). We hypothesized, however, that these proteins would not differ between women with non-obese and non-insulin resistant PCOS compared to matched control subjects. We measured plasma amyloid-related proteins levels (Amyloid-precursor protein (APP), alpha-synuclein (SNCA), amyloid P-component (APCS), Pappalysin (PAPPA), Microtubule-associated protein tau (MAPT), apolipoprotein E (apoE), apoE2, apoE3, apoE4, Serum amyloid A (SAA), Noggin (NOG) and apoA1) in weight and aged-matched non-obese PCOS (
MeSH term(s)	Female ; Humans ; Aged ; Polycystic Ovary Syndrome/metabolism ; Cross-Sectional Studies ; von Willebrand Factor ; Diabetes Mellitus, Type 2/complications ; Obesity/complications ; Apolipoproteins E/genetics ; Dementia/complications ; Insulin Resistance ; Body Mass Index ; Extracellular Matrix Proteins
Chemical Substances	von Willebrand Factor ; Apolipoproteins E ; ECM1 protein, human ; Extracellular Matrix Proteins
Language	English
Publishing date	2024-02-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25042409
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Article ; Online: Pancreatic β-cell heterogeneity in adult human islets and stem cell-derived islets.

Aldous, Noura / Moin, Abu Saleh Md / Abdelalim, Essam M

Cellular and molecular life sciences : CMLS

2023 Volume 80, Issue 6, Page(s) 176

Abstract: Recent studies reported that pancreatic β-cells are heterogeneous in terms of their transcriptional profiles and their abilities for insulin secretion. Sub-populations of pancreatic β-cells have been identified based on the functionality and expression ... ...

Abstract	Recent studies reported that pancreatic β-cells are heterogeneous in terms of their transcriptional profiles and their abilities for insulin secretion. Sub-populations of pancreatic β-cells have been identified based on the functionality and expression of specific surface markers. Under diabetes condition, β-cell identity is altered leading to different β-cell sub-populations. Furthermore, cell-cell contact between β-cells and other endocrine cells within the islet play an important role in regulating insulin secretion. This highlights the significance of generating a cell product derived from stem cells containing β-cells along with other major islet cells for treating patients with diabetes, instead of transplanting a purified population of β-cells. Another key question is how close in terms of heterogeneity are the islet cells derived from stem cells? In this review, we summarize the heterogeneity in islet cells of the adult pancreas and those generated from stem cells. In addition, we highlight the significance of this heterogeneity in health and disease conditions and how this can be used to design a stem cell-derived product for diabetes cell therapy.
MeSH term(s)	Humans ; Adult ; Insulin/metabolism ; Islets of Langerhans/metabolism ; Insulin-Secreting Cells/metabolism ; Diabetes Mellitus/metabolism ; Stem Cells
Chemical Substances	Insulin
Language	English
Publishing date	2023-06-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-023-04815-7
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Article ; Online: Complement Dysregulation in Obese Versus Nonobese Polycystic Ovary Syndrome Patients.

Butler, Alexandra E / Moin, Abu Saleh Md / Sathyapalan, Thozhukat / Atkin, Stephen L

Cells

2023 Volume 12, Issue 15

Abstract: Introduction: Upregulation of complement system factors are reported to be increased in polycystic ovary syndrome (PCOS) and may be due to obesity and insulin resistance rather than inherently due to PCOS. We directly compared complement factors from an ...

Abstract	Introduction: Upregulation of complement system factors are reported to be increased in polycystic ovary syndrome (PCOS) and may be due to obesity and insulin resistance rather than inherently due to PCOS. We directly compared complement factors from an obese, insulin-resistant PCOS population to a nonobese, non-insulin-resistant PCOS population in a proteomic analysis to investigate this. Methods: Plasma was collected from 234 women (137 with PCOS and 97 controls) from a biobank cohort and compared to a nonobese, non-insulin-resistant population (24 with PCOS and 24 controls). Slow off-rate modified aptamer (SOMA) scan plasma protein measurement was undertaken for the following complement system proteins: C1q, C1r, C2, C3, C3a, iC3b, C3b, C3d, C3adesArg, C4, C4a, C4b, C5, C5a, C5b-6 complex, C8, properdin, factor B, factor D, factor H, factor I, Mannose-binding protein C (MBL), complement decay-accelerating factor (DAF) and complement factor H-related protein 5 (CFHR5). Results: The alternative pathway of the complement system was overexpressed in both obese and nonobese PCOS, with increased C3 ( Conclusion: The upregulation of the alternative complement pathway was seen in nonobese PCOS and was further exacerbated in obese PCOS, indicating that this is an inherent feature of the pathophysiology of PCOS that is worsened by obesity and is reflected in the differences between the nonobese and obese PCOS phenotypes. However, the increase in the complement proteins associated with activation was counterbalanced by upregulation of complement inhibitors; this was evident in both PCOS groups, suggesting that insults, such as a cardiovascular event or infection, that cause activation of complement pathways may be amplified in PCOS.
Language	English
Publishing date	2023-08-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12152002
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Article ; Online: Coagulation factor dysregulation in polycystic ovary syndrome is an epiphenomenon of obesity.

Moin, Abu Saleh Md / Sathyapalan, Thozhukat / Butler, Alexandra E / Atkin, Stephen L

Clinical endocrinology

2023 Volume 98, Issue 6, Page(s) 796–802

Abstract: Objective: Obese women with polycystic ovary syndrome (PCOS) exhibit a hypercoagulable state, with the suggestion that this may be obesity-driven rather than an intrinsic facet of PCOS; however, this has not yet been definitively determined since body ... ...

Abstract	Objective: Obese women with polycystic ovary syndrome (PCOS) exhibit a hypercoagulable state, with the suggestion that this may be obesity-driven rather than an intrinsic facet of PCOS; however, this has not yet been definitively determined since body mass index (BMI) is so highly correlated with PCOS. Therefore, only a study design where obesity, insulin resistance and inflammation are matched can answer this question. Design: This was a cohort study. Patients Weight and aged-matched nonobese women with PCOS (n = 29) and control women (n = 29) were included. Measurements Plasma coagulation pathway protein levels were measured. Circulating levels of a panel of nine clotting proteins known to differ in obese women with PCOS were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement. Results: Women with PCOS showed a higher free androgen index (FAI) and anti-Müllerian hormone, but measures of insulin resistance, and C reactive protein (as a marker of inflammation), did not differ between the nonobese women with PCOS and the control women. Seven pro-coagulation proteins (plasminogen activator inhibitor-1, fibrinogen, fibrinogen gamma chain, fibronectin, d-dimer, P-selectin and plasma kallikrein) and two anticoagulant proteins (vitamin K-dependent protein-S and heparin cofactor-II) known to be elevated in obese women with PCOS did not differ from controls in this cohort. Conclusions: This novel data show that clotting system abnormalities do not contribute to the intrinsic mechanisms underlying PCOS in this nonobese noninsulin resistant population of women with PCOS matched for age and BMI, and without evidence of underlying inflammation, but rather the clotting factor changes are an epiphenomenon coincident with obesity; therefore, increased coagulability is unlikely in these nonobese PCOS women.
MeSH term(s)	Humans ; Female ; Aged ; Polycystic Ovary Syndrome ; Insulin Resistance ; Cohort Studies ; Obesity ; Inflammation ; Fibrinogen ; Body Mass Index ; Insulin
Chemical Substances	Fibrinogen (9001-32-5) ; Insulin
Language	English
Publishing date	2023-03-08
Publishing country	England
Document type	Journal Article
ZDB-ID	121745-8
ISSN	1365-2265 ; 0300-0664
ISSN (online)	1365-2265
ISSN	0300-0664
DOI	10.1111/cen.14904
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Article ; Online: Correction to: COVID-19 biomarkers for severity mapped to polycystic ovary syndrome.

Moin, Abu Saleh Md / Sathyapalan, Thozhukat / Atkin, Stephen L / Butler, Alexandra E

Journal of translational medicine

2021 Volume 19, Issue 1, Page(s) 106

Language	English
Publishing date	2021-03-15
Publishing country	England
Document type	Published Erratum
ISSN	1479-5876
ISSN (online)	1479-5876
DOI	10.1186/s12967-021-02782-w
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Article ; Online: The relationship of soluble neuropilin-1 to severe COVID-19 risk factors in polycystic ovary syndrome.

Moin, Abu Saleh Md / Sathyapalan, Thozhukat / Atkin, Stephen L / Butler, Alexandra E

Metabolism open

2021 Volume 9, Page(s) 100079

Language	English
Publishing date	2021-01-18
Publishing country	England
Document type	Journal Article
ISSN	2589-9368
ISSN (online)	2589-9368
DOI	10.1016/j.metop.2021.100079
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Article ; Online: Therapeutic Applications of Stem Cell-Derived Exosomes.

Abdulmalek, Omar Abdulhakeem Ahmed Yusuf / Husain, Khaled Hameed / AlKhalifa, Haya Khaled Ali Abdulla / Alturani, Mariam Masood Abdulkarim Bahrooz / Butler, Alexandra E / Moin, Abu Saleh Md

International journal of molecular sciences

2024 Volume 25, Issue 6

Abstract: Exosomes are extracellular vesicles of endosomal origin, ranging from 30 to 150 nm in diameter, that mediate intercellular transfer of various biomolecules, such as proteins, lipids, nucleic acids, and metabolites. They modulate the functions of ... ...

Abstract	Exosomes are extracellular vesicles of endosomal origin, ranging from 30 to 150 nm in diameter, that mediate intercellular transfer of various biomolecules, such as proteins, lipids, nucleic acids, and metabolites. They modulate the functions of recipient cells and participate in diverse physiological and pathological processes, such as immune responses, cell-cell communication, carcinogenesis, and viral infection. Stem cells (SCs) are pluripotent or multipotent cells that can differentiate into various cell types. SCs can also secrete exosomes, which exhibit remarkable therapeutic potential for various diseases, especially in the field of regenerative medicine. For example, exosomes derived from mesenchymal stem cells (MSCs) contain proteins, lipids, and miRNAs that can ameliorate endocrine disorders, such as diabetes and cancer. Exosomes from SCs (sc-exos) may offer similar advantages as SCs, but with reduced risks and challenges. Sc-exos have lower tumorigenicity, immunogenicity, and infectivity. They can also deliver drugs more efficiently and penetrate deeper into tissues. In this review, we provide an overview of the recent advances in sc-exos and their therapeutic applications in various diseases, such as diabetes and cancer. We also elucidate how the biological effects of sc-exos depend on their molecular composition. We also address the current challenges and future directions of using sc-exos.
MeSH term(s)	Humans ; Exosomes/metabolism ; Stem Cells ; Neoplasms/therapy ; Neoplasms/metabolism ; Diabetes Mellitus/therapy ; Diabetes Mellitus/metabolism ; Lipids
Chemical Substances	Lipids
Language	English
Publishing date	2024-03-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25063562
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Article ; Online: The Role of Heat Shock Proteins in the Pathogenesis of Polycystic Ovarian Syndrome: A Review of the Literature.

Niinuma, Sara Anjum / Lubbad, Laila / Lubbad, Walaa / Moin, Abu Saleh Md / Butler, Alexandra E

International journal of molecular sciences

2023 Volume 24, Issue 3

Abstract: Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and post-menopausal women. PCOS is a multifactorial heterogeneous disorder associated with a variety of etiologies, outcomes, and clinical ... ...

Abstract	Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and post-menopausal women. PCOS is a multifactorial heterogeneous disorder associated with a variety of etiologies, outcomes, and clinical manifestations. However, the pathophysiology of PCOS is still unclear. Heat shock proteins (HSPs) have recently been investigated for their role in the pathogenesis of PCOS. HSPs are a class of proteins that act as molecular chaperones and maintain cellular proteostasis. More recently, their actions beyond that of molecular chaperones have highlighted their pathogenic role in several diseases. In PCOS, different HSP family members show abnormal expression that affects the proliferation and apoptotic rates of ovarian cells as well as immunological processes. HSP dysregulation in the ovaries of PCOS subjects leads to a proliferation/apoptosis imbalance that mechanistically impacts follicle stage development, resulting in polycystic ovaries. Moreover, HSPs may play a role in the pathogenesis of PCOS-associated conditions. Recent studies on HSP activity during therapeutic interventions for PCOS suggest that modulating HSP activity may lead to novel treatment strategies. In this review, we summarize what is currently known regarding the role of HSPs in the pathogenesis of PCOS and their potential role in the treatment of PCOS, and we outline areas for future research.
MeSH term(s)	Female ; Humans ; Polycystic Ovary Syndrome/metabolism ; Heat-Shock Proteins ; Reproduction
Chemical Substances	Heat-Shock Proteins
Language	English
Publishing date	2023-01-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24031838
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