scholarly journals Diabetic Nephropathy and COVID-19: The Potential Role of Immune Actors

2021 ◽  
Vol 22 (15) ◽  
pp. 7762
Author(s):  
Diane Mourad ◽  
Nadim S. Azar ◽  
Sami T. Azar
Keyword(s):  
Diabetic Nephropathy ◽  
Viral Entry ◽  
Type Ii Diabetes ◽  
Potential Role ◽  
Underlying Mechanism ◽  
Type Ii Diabetes Mellitus ◽  
Angiotensin Converting Enzyme 2 ◽  
Neuropilin 1 ◽  
Mitochondrial Glutathione

Nowadays, type II diabetes mellitus, more specifically ensuing diabetic nephropathy, and severe COVID-19 disease are known to be closely associated. The exact mechanisms behind this association are less known. An implication for the angiotensin-converting enzyme 2 remains controversial. Some researchers have started looking into other potential actors, such as neuropilin-1, mitochondrial glutathione, vitamin D, and DPP4. In particular, neuropilin-1 seems to play an important role in the underlying mechanism linking COVID-19 and diabetic nephropathy. We suggest, based on the findings in this review, that its up-regulation in the diabetic kidney facilitates viral entry in this tissue, and that the engagement of both processes leads to a depletion of neuropilin-1, which was demonstrated to be strongly associated with the pathogenesis of DN. More studies are needed to confirm this hypothesis, and research should be directed towards elucidating the potential roles of all these suggested actors and eventually discovering new therapeutic strategies that could reduce the burden of COVID-19 in patients with diabetic nephropathy.

1027 POTENTIAL ROLE OF MIR-93 IN TYPE II DIABETES MELLITUS-INDUCED ERECTILE DYSFUNCTION

2013 ◽  
Vol 189 (4S) ◽  
Author(s):  
Carlos Barbery ◽  
Cara Cimmino ◽  
Sung Tae Cho ◽  
Brian Annex ◽  
Lysiak Jeffrey
Keyword(s):  
Diabetes Mellitus ◽  
Erectile Dysfunction ◽  
Type Ii Diabetes ◽  
Potential Role ◽  
Type Ii Diabetes Mellitus ◽  
Type Ii

It Takes Two to Tango: Secondary Entry Pathway for SARS-CoV-2 Induces Analgesia

2021 ◽  
Author(s):  
R. Weill Rossi
Keyword(s):  
Viral Entry ◽  
Therapeutic Strategies ◽  
Mechanisms Of Action ◽  
Vascular Endothelial ◽  
Angiotensin Converting Enzyme 2 ◽  
Entry Pathway ◽  
Neuropilin 1 ◽  
New Compounds ◽  
Endothelial Growth Factor

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to impact the world, its mechanisms of action begin to unravel. The main entry pathway for SARS-CoV-2 into the cell is thought to be through binding to the angiotensin converting enzyme 2, but it seems another protein can induce its viral entry: neuropilin-1 receptor (NRP-1). NRP-1 is usually bound by vascular endothelial growth factor-A (VEGF-A), a - amongst other- pronociceptive factor. By binding to NRP-1, the Spike protein of SARS-CoV-2 blocks neuronal signaling, reducing the pro-nociceptive implication of VEGF-A. This analgesic role of SARS-CoV-2 gave rise to an increase in screenings for new compounds that could interfere with this pathway. Preventing VEGFA from binding to NRP1 opens new possibilities for therapeutic strategies in the field of neuropathic pain.

scholarly journals ACE2 Shedding and the Role in COVID-19

2022 ◽  
Vol 11 ◽  
Author(s):  
Jieqiong Wang ◽  
Huiying Zhao ◽  
Youzhong An
Keyword(s):  
Amino Acids ◽  
Viral Entry ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Underlying Mechanism ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Transmembrane Glycoprotein

Angiotensin converting enzyme 2 (ACE2), a transmembrane glycoprotein, is an important part of the renin-angiotensin system (RAS). In the COVID-19 epidemic, it was found to be the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). ACE2 maintains homeostasis by inhibiting the Ang II-AT1R axis and activating the Ang I (1-7)-MasR axis, protecting against lung, heart and kidney injury. In addition, ACE2 helps transport amino acids across the membrane. ACE2 sheds from the membrane, producing soluble ACE2 (sACE2). Previous studies have pointed out that sACE2 plays a role in the pathology of the disease, but the underlying mechanism is not yet clear. Recent studies have confirmed that sACE2 can also act as the receptor of SARS-COV-2, mediating viral entry into the cell and then spreading to the infective area. Elevated concentrations of sACE2 are more related to disease. Recombinant human ACE2, an exogenous soluble ACE2, can be used to supplement endogenous ACE2. It may represent a potent COVID-19 treatment in the future. However, the specific administration concentration needs to be further investigated.

scholarly journals OX40L/OX40 Signal Promotes IL-9 Production by Mucosal MAIT Cells During Helicobacter pylori Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Siqi Ming ◽  
Mei Zhang ◽  
Zibin Liang ◽  
Chunna Li ◽  
Jianzhong He ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Potential Role ◽  
Critical Role ◽  
Underlying Mechanism ◽  
Mucosal Inflammation ◽  
Cross Linking ◽  
Mait Cells ◽  
H Pylori ◽  
Mait Cell

Mucosal associated invariant T (MAIT) cells play a critical role in Helicobacter pylori (H. pylori)-induced gastritis by promoting mucosal inflammation and aggravating mucosal injuries (1, 2). However, the underlying mechanism and key molecules involved are still uncertain. Here we identified OX40, a co-stimulatory molecule mainly expressed on T cells, as a critical regulator to promote proliferation and IL-9 production by MAIT cells and facilitate mucosal inflammation in H. pylori-positive gastritis patients. Serum examination revealed an increased level of IL-9 in gastritis patients. Meanwhile, OX40 expression was increased in mucosal MAIT cells, and its ligand OX40L was also up-regulated in mucosal dendritic cells (DCs) of gastritis patients, compared with healthy controls. Further results demonstrated that activation of the OX40/OX40L pathway promoted IL-9 production by MAIT cells, and MAIT cells displayed a highly-activated phenotype after the cross-linking of OX40 and OX40L. Moreover, the level of IL-9 produced by MAIT cells was positively correlated with inflammatory indexes in the gastric mucosa, suggesting the potential role of IL-9-producing MAIT cells in mucosal inflammation. Taken together, we elucidated that OX40/OX40L axis promoted mucosal MAIT cell proliferation and IL-9 production in H. pylori-induced gastritis, which may provide potential targeting strategies for gastritis treatment.

scholarly journals The role of Neuropilin-1 in COVID-19

2021 ◽  
Vol 17 (1) ◽  
pp. e1009153
Author(s):  
Bindu S. Mayi ◽  
Jillian A. Leibowitz ◽  
Arden T. Woods ◽  
Katherine A. Ammon ◽  
Alphonse E. Liu ◽  
...  
Keyword(s):  
Immune Function ◽  
Viral Entry ◽  
Axonal Guidance ◽  
Cell Surface Receptor ◽  
Neuropilin 1 ◽  
Surface Receptor ◽  
The Central Nervous System

Neuropilin-1 (NRP-1), a member of a family of signaling proteins, was shown to serve as an entry factor and potentiate SARS Coronavirus 2 (SARS-CoV-2) infectivity in vitro. This cell surface receptor with its disseminated expression is important in angiogenesis, tumor progression, viral entry, axonal guidance, and immune function. NRP-1 is implicated in several aspects of a SARS-CoV-2 infection including possible spread through the olfactory bulb and into the central nervous system and increased NRP-1 RNA expression in lungs of severe Coronavirus Disease 2019 (COVID-19). Up-regulation of NRP-1 protein in diabetic kidney cells hint at its importance in a population at risk of severe COVID-19. Involvement of NRP-1 in immune function is compelling, given the role of an exaggerated immune response in disease severity and deaths due to COVID-19. NRP-1 has been suggested to be an immune checkpoint of T cell memory. It is unknown whether involvement and up-regulation of NRP-1 in COVID-19 may translate into disease outcome and long-term consequences, including possible immune dysfunction. It is prudent to further research NRP-1 and its possibility of serving as a therapeutic target in SARS-CoV-2 infections. We anticipate that widespread expression, abundance in the respiratory and olfactory epithelium, and the functionalities of NRP-1 factor into the multiple systemic effects of COVID-19 and challenges we face in management of disease and potential long-term sequelae.

scholarly journals The Nrf2/Keap1/ARE Pathway and Oxidative Stress as a Therapeutic Target in Type II Diabetes Mellitus

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Joshua A. David ◽  
William J. Rifkin ◽  
Piul S. Rabbani ◽  
Daniel J. Ceradini
Keyword(s):  
Diabetes Mellitus ◽  
Oxidative Damage ◽  
Therapeutic Target ◽  
Type Ii Diabetes ◽  
Animal Studies ◽  
Cell Types ◽  
Type Ii Diabetes Mellitus ◽  
Type Ii ◽  
And Oxidative Stress

Despite improvements in awareness and treatment of type II diabetes mellitus (TIIDM), this disease remains a major source of morbidity and mortality worldwide, and prevalence continues to rise. Oxidative damage caused by free radicals has long been known to contribute to the pathogenesis and progression of TIIDM and its complications. Only recently, however, has the role of the Nrf2/Keap1/ARE master antioxidant pathway in diabetic dysfunction begun to be elucidated. There is accumulating evidence that this pathway is implicated in diabetic damage to the pancreas, heart, and skin, among other cell types and tissues. Animal studies and clinical trials have shown promising results suggesting that activation of this pathway can delay or reverse some of these impairments in TIIDM. In this review, we outline the role of oxidative damage and the Nrf2/Keap1/ARE pathway in TIIDM, focusing on current and future efforts to utilize this relationship as a therapeutic target for prevention, prognosis, and treatment of TIID.

Role of yoga for patients with type II diabetes mellitus: A systematic review and meta-analysis

2016 ◽  
Vol 25 ◽  
pp. 104-112 ◽  
Author(s):  
Vinod Kumar ◽  
Aarti Jagannathan ◽  
Mariamma Philip ◽  
Arun Thulasi ◽  
Praveen Angadi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Systematic Review ◽  
Type Ii Diabetes ◽  
Meta Analysis ◽  
Type Ii Diabetes Mellitus ◽  
Type Ii

scholarly journals Is There a Link between Bisphenol A (BPA), a Key Endocrine Disruptor, and the Risk for SARS-CoV-2 Infection and Severe COVID-19?

2020 ◽  
Vol 9 (10) ◽  
pp. 3296
Author(s):  
Aeman Zahra ◽  
Cristina Sisu ◽  
Elisabete Silva ◽  
Sophie-Christine De Aguiar Greca ◽  
Harpal S. Randeva ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Potential Role ◽  
Metabolic Diseases ◽  
Endocrine Disrupting Chemicals ◽  
Angiotensin Converting Enzyme 2 ◽  
Endocrine Disrupting ◽  
Membrane Bound ◽  
Transmembrane Serine Protease ◽  
G Protein Coupled

Infection by the severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) is the causative agent of a new disease (COVID-19). The risk of severe COVID-19 is increased by certain underlying comorbidities, including asthma, cancer, cardiovascular disease, hypertension, diabetes, and obesity. Notably, exposure to hormonally active chemicals called endocrine-disrupting chemicals (EDCs) can promote such cardio-metabolic diseases, endocrine-related cancers, and immune system dysregulation and thus, may also be linked to higher risk of severe COVID-19. Bisphenol A (BPA) is among the most common EDCs and exerts its effects via receptors which are widely distributed in human tissues, including nuclear oestrogen receptors (ERα and ERβ), membrane-bound oestrogen receptor (G protein-coupled receptor 30; GPR30), and human nuclear receptor oestrogen-related receptor gamma. As such, this paper focuses on the potential role of BPA in promoting comorbidities associated with severe COVID-19, as well as on potential BPA-induced effects on key SARS-CoV-2 infection mediators, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Interestingly, GPR30 appears to exhibit greater co-localisation with TMPRSS2 in key tissues like lung and prostate, suggesting that BPA exposure may impact on the local expression of these SARS-CoV-2 infection mediators. Overall, the potential role of BPA on the risk and severity of COVID-19 merits further investigation.

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