Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. The hallmarks are the presence of Lewy bodies composed ...mainly of aggregated α‐synuclein and immune activation and inflammation in the brain. The neurotropism of SARS‐CoV‐2 with induction of cytokine storm and neuroinflammation can contribute to the development of PD. Interestingly, overexpression of α‐synuclein in PD patients may limit SARS‐CoV‐2 neuroinvasion and degeneration of dopaminergic neurons; however, on the other hand, this virus can speed up the α‐synuclein aggregation. The review aims to discuss the potential link between COVID‐19 and the risk of PD, highlighting the need for further studies to authenticate the potential association. We have also overviewed the influence of SARS‐CoV‐2 infection on the PD course and management. In this context, we presented the prospects for controlling the COVID‐19 pandemic and related PD cases that, beyond global vaccination and novel anti‐SARS‐CoV‐2 agents, may include the development of graphene‐based nanoscale platforms offering antiviral and anti‐amyloid strategies against PD.
The aim of the present study was to investigate the probable effects of metformin plus vildagliptin on the oxidative stress index (OSI) in patients with type II diabetes mellitus (T2DM). In this ...case-control study, 44 patients with T2DM on either metformin monotherapy (n = 24) or metformin plus vildagliptin (n = 20) were compared with healthy controls (n = 20). Anthropometric and biochemical variables including body mass index, blood pressure profile, cardiac indices, lipid profile, fasting blood glucose, fasting serum insulin, and glycemic indices were assessed. Besides, total oxidant status (TOS), total antioxidant status (TAS), and OSI were determined. Patients with T2DM have higher risk of cardiometabolic changes compared with the control (P = 0.0001). TAS was lower while TOS and OSI were higher in patients with T2DM, as compared with the healthy controls (P < 0.001). TAS, TOS, and OSI were better in patients with T2DM on metformin plus vildagliptin therapy as compared with metformin monotherapy (P < 0.05). Therefore, this study concluded that metformin plus vildagliptin therapy is more effective than metformin monotherapy in attenuation of OSI in patients with T2DM.
In Covid-19, systemic disturbances may progress due to development of cytokine storm and dysregulation of and plasma osmolarility due to high release of pro-inflammatory cytokines and neuro-hormonal ...disorders. Arginine vasopressin (AVP) which is involve in the regulation of body osmotic system, body water content, blood pressure and plasma volume, that are highly disturbed in Covid-19 and linked with poor clinical outcomes. Therefore, this present study aimed to find the potential association between AVP serum level and inflammatory disorders in Covid-19. It has been observed by different recent studies that physiological response due to fever, pain, hypovolemia, dehydration, and psychological stress is characterized by activation release of AVP to counter-balance high blood viscosity in Covid-19 patients. In addition, activated immune cells mainly T and B lymphocytes and released pro-inflammatory cytokines stimulate discharge of stored AVP from immune cells, which in a vicious cycle trigger release of pro-inflammatory cytokines. Vasopressin receptor antagonists have antiviral and anti-inflammatory effects that may inhibit AVP-induced hyponatremia and release of pro-inflammatory cytokines in Covid-19. In conclusion, release of AVP from hypothalamus is augmented in Covid-19 due to stress, high pro-inflammatory cytokines, high circulating AngII and inhibition of GABAergic neurons. In turn, high AVP level leads to induction of hyponatremia, inflammatory disorders, and development of complications in Covid-19 by activation of NF-κB and NLRP3 inflammasome with release of pro-inflammatory cytokines. Therefore, AVP antagonists might be novel potential therapeutic modality in treating Covid-19 through mitigation of AVP-mediated inflammatory disorders and hyponatremia.
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•Covid-19 is associated with dysregulation of plasma osmolarility due to release of cytokines and neuro-hormonal disorders.•Arginine vasopressin (AVP) is increased due to fever and dehydration to counter high blood viscosity in Covid-19 patients.•T and B lymphocytes as well as pro-inflammatory cytokines stimulate discharge of stored AVP from immune cells in Covid-19.•High AVP levels lead to hyponatremia and inflammatory disorders by activation of NF-κB and NLRP3 inflammasome.•Vasopressin receptor antagonists have antiviral and anti-inflammatory effects that may inhibit progression of Covid-19.
Obesity refers to an excess of body fat content causing metabolic and inflammatory disorders. Therefore, the aim of the present study was to investigate dose-dependent effect of rosuvastatin on the ...metabolic profile of diet-induced obesity in mice model study. A total number of 40 male Albino Swiss mice were used which divided into Group I: Control group, fed normal diet for 8 weeks (n = 10); Group II: High-fat diet (HFD) group, fed on HFD for 8 weeks (n = 10); Group III: HFD + 20 mg/kg rosuvastatin for 8 weeks (n = 10); and Group IV: HFD +40 mg/kg rosuvastatin for 8 weeks (n = 10). Anthropometric and biochemical parameters were estimated, including fasting blood glucose, lipid profile, fasting insulin, and glucose tolerance test (GTT). Mice on HFD fed showed a significant increase in the insulin resistance, body weight, deterioration of lipid profile and significant reduction in the β-cell function, and insulin sensitivity compared to the control P < 0.05. GTT and blood glucose level were significantly high in HFD fed group compared to the control group P < 0.05. Rosuvastatin in a dose of 40 mg/kg illustrated better effect than 20 mg/kg on the glucometabolic profile P < 0.05. Rosuvastatin may has a potential effect on reduction of glucometabolic changes induced by HFD with significant amelioration of pancreatic β-cell function in dose-dependent manner.
COVID-19 is caused by SARS-CoV-2 and leads to acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and extrapulmonary manifestations in severely affected cases. However, most of the ...affected cases are mild or asymptomatic. Cannabinoids (CBs) such as tetrahydrocannabinol (THC) and cannabidiol (CBD), which act on G-protein-coupled receptors called CB1 and CB2, have anti-inflammatory effects. Many published studies show that CBs are effective in various inflammatory disorders, viral infections, and attenuation of ALI and ARDS. Therefore, the present narrative review aimed to summarize the possible immunological role of CBs in COVID-19. The effects of CBs are controversial, although they have beneficial effects via CB2 receptors and adverse effects via CB1 receptors against ALI, ARDS, and hyperinflammation, which are hallmarks of COVID-19. The present narrative review has shown that CBs effectively manage ALI and ARDS by suppressing pro-inflammatory cytokines, which are common in COVID-19. Therefore, CBs may be used to manage COVID-19 because of their potent anti-inflammatory effects, suppressing pro-inflammatory cytokines and inhibiting inflammatory signaling pathways.
Nephrotoxicity is defining as rapid deterioration in the kidney function due to toxic effect of medications and chemicals. There are various forms, and some drugs may affect renal function in more ...than one way. Nephrotoxins are substances displaying nephrotoxicity. Different mechanisms lead to nephrotoxicity, including renal tubular toxicity, inflammation, glomerular damage, crystal nephropathy, and thrombotic microangiopathy. The traditional markers of nephrotoxicity and renal dysfunction are blood urea and serum creatinine which are regarded as low sensitive in the detection of early renal damage. Thus, the detection of the initial renal injures required new biomarkers which are more sensitive and highly specific that gives an insight into the site of underlying renal damage. Kidney injury molecule-1, Cystatin C, and neutrophil gelatinase-associated lipocalin sera levels are more sensitive than blood urea and serum creatinine in the detection of acute kidney injury during nephrotoxicity.
Coronavirus disease 19 (COVID-19) is regarded as an independent risk factor for acute ischemic stroke (AIS) due to the induction of endothelial dysfunction, coagulopathy, cytokine storm, and plaque ...instability.
In this retrospective cohort study, a total of 42 COVID-19 patients with type 2 diabetes mellitus (T2DM) who presented with AIS within 1 week of displaying COVID-19 symptoms were recruited. According to the current anti-DM pharmacotherapy, patients were divided into two groups: a Metformin group of T2DM patients with COVID-19 and AIS on metformin therapy (850 mg, 3 times daily (
= 22), and a Non-metformin group of T2DM patients with COVID-19 and AIS under another anti-DM pharmacotherapy like glibenclamide and pioglitazone (
= 20). Anthropometric, biochemical, and radiological data were evaluated.
Ferritin serum level was lower in metformin-treated patients compared to non-metformin treated patients (365.93 ± 17.41 vs. 475.92 ± 22.78 ng/mL,
= 0.0001). CRP, LDH, and D-dimer serum levels were also lowered in metformin-treated patients compared to non-metformin treated patients (
= 0.0001). In addition, lung CT scan scores of COVID-19 patients was 30.62 ± 10.64 for metformin and 36.31 ± 5.03 for non-metformin treated patients.
Metformin therapy in T2DM patients was linked to a lower risk of AIS during COVID-19. Further studies are needed to observe the link between AIS in COVID-19 diabetic patients and metformin therapy.
Parkinson's disease (PD) is the second most frequent neurodegenerative brain disease (NBD) after Alzheimer's disease (AD). Statins are the most common lipid‐lowering agents used in the management of ...dyslipidemia and the prevention of primary and secondary cardiovascular diseases (CVD) events. In addition, there is a controversial point regarding the role of serum lipids in the pathogenesis of PD. In this bargain, as statins reduce serum cholesterol so they affect the PD neuropathology in bidirectional ways either protective or harmful. Statins are not used in the management of PD, but they are frequently used in the cardiovascular disorders commonly associated with PD in the elderly population. Therefore, the use of statins in that population may affect PD outcomes. Concerning the potential role of statins on PD neuropathology, there are conflicts and controversies either protective against the development of PD or harmful by increasing the risk for the development of PD. Therefore, this review aimed to clarify the precise role of statins in PD regarding the pros and cons from published studies. Many studies suggest a protective role of statins against PD risk through the modulation of inflammatory and lysosomal signaling pathways. Nevertheless, other observations suggest that statin therapy may increase PD risk by diverse mechanisms including reduction of CoQ10. In conclusion, there are strong controversies regarding the protective role of statins in PD neuropathology. Therefore, retrospective and prospective studies are necessary in this regard.
Type 2 diabetes mellitus (T2DM) is a chronic endocrine disorder due to the reduction of insulin sensitivity and relative deficiency of insulin secretion. Growth differentiation factor 15 (GDF15) ...belongs to the transforming growth factor beta (TGF‐β) superfamily and was initially identified as macrophage inhibitory cytokine‐1 (MIC‐1). GDF15 is considered a cytokine with an anti‐inflammatory effect and increases insulin sensitivity, reduces body weight, and improves clinical outcomes in diabetic patients. GDF15 acts through stimulation of glial‐derived neurotrophic factor (GDNF) family receptor α‐like (GFRAL), which is highly expressed in the brain stem to induce taste aversion. Metformin belongs to the group of biguanides that are derived from the plant Galega officinalis. It is interesting to note that metformin is an insulin‐sensitizing agent used as a first‐line therapy for T2DM that has been shown to increase the circulating level of GDF15. Thus, the present review aims to determine the critical association of the GDF15 biomarker in T2DM and how metformin agents affect it. This review illustrates that metformin activates GDF15 expression, which reduces appetite and leads to weight loss in both diabetic and nondiabetic patients. However, the present review cannot give a conclusion in this regard. Therefore, experimental, preclinical, and clinical studies are warranted to confirm the potential role of GDF15 in T2DM patients.
摘要
2型糖尿病(T2DM)是一种因胰岛素敏感性降低和胰岛素分泌相对不足而引起的慢性内分泌疾病。生长分化因子15 (GDF15)属于转化生长因子‐β (TGF‐β)超家族，最初被鉴定为巨噬细胞抑制因子‐1 (MIC)。GDF15被认为是一种具有抗炎作用、增加胰岛素敏感性、减轻体重和改善糖尿病患者临床疗效的细胞因子。GDF15通过刺激脑干高表达的胶质源性神经营养因子(GDNF)家族受体α样(GFRAL)诱导味觉厌恶。二甲双胍属于从大戟属植物中提取的双胍类化合物。二甲双胍是一种胰岛素增敏剂，用于T2DM的一线治疗，已被证明可增加GDF15的循环水平。本综述旨在确定GDF15生物标志物在T2DM中的关键作用以及二甲双胍药物是如何影响它发。综述表明，二甲双胍激活GDF15的表达，降低糖尿病和非糖尿病患者的食欲，诱导体重减轻。然而，目前的研究无法在这方面给出结论。因此，有必要进行实验、临床前和临床研究来确认GDF15在T2DM患者中的潜在作用。
Highlights
Metformin activates GDF15 expression, which reduces appetite with induction of weight loss in both diabetic and non‐diabetic patients.
GDF15 level is linked and correlated with the progression of diabetic complications including thrombosis, diabetic nephropathy, diabetic neuropathy, and diabetic retinopathy.
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