Impacts of Supplementation with Silymarin on Cardiovascular Risk Factors: A Systematic Review and Dose-Response Meta-Analysis.

It has been suggested that silymarin (SIL) supplementation has positive effects on cardiovascular health and reduces the risk of cardiometabolic syndrome (CMS). This systematic review and dose-response meta-analysis assessed the impacts of SIL administration on cardiovascular risk factors. A systematic search of multiple databases was performed to identify eligible controlled trials published up to January 2023. The analysis used a random-effects model and included 33 trials with 1943 participants. It was revealed that SIL supplementation led to a notable reduction in serum levels of fasting blood glucose (FBG) (weighted mean difference (WMD): -21.68 mg/dL, 95% CI: -31.37, -11.99; p < 0.001), diastolic blood pressure (DBP) (WMD: -1.25 mmHg; 95% CI: -2.25, -0.26; p = 0.013), total cholesterol (TC) (WMD: -13.97 mg/dL, 95% CI: -23.09, -4.85; p = 0.003), triglycerides (TG) (WMD: -26.22 mg/dL, 95% CI: -40.32, -12.12; p < 0.001), fasting insulin (WMD: -3.76 mU/mL, 95% CI: -4.80, -2.72; p < 0.001), low-density lipoprotein (LDL) (WMD: -17.13 mg/dL, 95% CI: -25.63, -8.63; p < 0.001), and hemoglobin A1C (HbA1c) (WMD: -0.85%, 95% CI: -1.27, -0.43; p < 0.001) in the SIL-treated groups compared to their untreated counterparts. In addition, there were no substantial differences in body mass index (BMI), systolic blood pressure (SBP), C-reactive protein (CRP), body weight, and high-density lipoprotein (HDL) between the two groups. These outcomes suggest that SIL consumption reduces certain CMS risk factors and has favorable impacts on lipid and glycemic profiles with potential hypotensive effects. These findings should be supported by additional trials with larger sample sizes and longer durations.

Effects of silymarin supplementation on liver and kidney functions: A systematic review and dose-response meta-analysis.

It is suggested that supplementation with silymarin (SIL) has beneficial impacts on kidney and liver functions. This systematic review and dose-response meta-analysis assessed the impact of SIL administration on certain hepatic, renal, and oxidative stress markers. A systematic search was conducted in various databases to identify relevant trials published until January 2023. Randomized controlled trials (RCTs) that evaluated the effects of SIL on kidney and liver markers were included. A random-effects model was used for the analysis and 41 RCTs were included. The pooled results indicated that SIL supplementation led to a significant reduction in serum levels of alkaline phosphatase, alanine transaminase, creatinine, and aspartate aminotransferase, along with a substantial elevation in serum glutathione in the SIL-treated group compared to their untreated counterparts. In addition, there was a nonsignificant decrease in serum levels of gamma-glutamyl transferase, malondialdehyde (MDA), total bilirubin, albumin (Alb), total antioxidant capacity, and blood urea nitrogen. Sub-group analyses revealed a considerable decline in MDA and Alb serum values among SIL-treated participants with liver disease in trials with a longer duration (≥12 weeks). These findings suggest that SIL may ameliorate certain liver markers with potential hepatoprotective effects, specifically with long-term and high-dose supplementation. However, its nephroprotective effects and impact on oxidative stress markers were not observed. Additional high-quality RCTs with longer durations are required to determine the clinical efficacy of SIL supplementation on renal and oxidative stress markers.

CCN3/NOV Serum Levels in Non-Alcoholic Fatty Liver Disease (NAFLD) Patients in Comparison with the Healthy Group and their Correlation with TNF-α and IL-6.

INTRODUCTION: Adipokine irregularity leads to inflammation, endothelial dysfunction, insulin resistance (IR), and Non-Alcoholic Fatty Liver Disease (NAFLD). Previous studies linked NOV/CCN3 to obesity, IR, and inflammation, but no research has explored the connection between CCN3 serum levels and NAFLD. METHODS: This case-control study assessed CCN3, IL-6, adiponectin, and TNF-α serum levels in 80 NAFLD patients and 80 controls using ELISA kits. Biochemical parameters were measured with commercial kits and an auto analyzer. RESULTS: NAFLD patients exhibited significantly higher CCN3 (2399.85 ± 744.53 vs. 1712.84 ± 478.19 ng/ml), TNF-α, and IL-6 levels, and lower adiponectin levels compared to controls (P<0.0001). In the NAFLD group, CCN3 showed positive correlations with FBG, insulin, HOMA-IR, and TNF-α. Binary logistic regression analysis revealed increased NAFLD risk in the adjusted model (OR [95% CI] = 1.220 [1.315 -1.131]). A CCN3 cut-off value of 1898.0050 pg/mL differentiated NAFLD patients from controls with 78.8% sensitivity and 73.2% specificity. CONCLUSION: It was found that elevated CCN3 serum levels directly correlate with NAFLD incidence and inflammation markers (IL-6 and TNF-α). CCN3 could serve as a potential biomarker for NAFLD, but further research is needed to validate this finding and assess its clinical utility.

The effects of beetroot and nitrate supplementation on body composition: a GRADE-assessed systematic review and meta-analysis.

This systematic review and meta-analysis aimed to investigate the effects of beetroot (BR) or nitrate supplements on body composition indices. A systematic search was conducted for randomised controlled trials (RCT) published up to August 2022 among online databases including Scopus, PubMed/Medline, Web of Science and Embase. Meta-analyses were carried out using a random-effects model. The I2 index was used to assess the heterogeneity of RCT. A total of twelve RCT met the inclusion criteria for this meta-analysis. The pooled effect size of included studies indicated that BR or nitrate supplementation did not change body weight (weighted mean differences (WMD): -0·14 kg, 95 % CI -1·22, 1·51; P = 0·836; I2 = 0 %), BMI (WMD: -0·07 kg/m2, 95 % CI -0·19,0·03; P = 0·174, I2 = 0 %), fat mass (WMD: -0·26 kg, 95 % CI -1·51, 0·98; P = 0·677, I2 = 0 %), waist circumference (WMD: -0·28 cm, 95 % CI -2·30, 1·74; P = 0·786, I2 = 0 %), body fat percentage (WMD: 0·18 %, 95 % CI -0·62, 0·99; P = 0·651, I2 = 0 %), fat-free mass (WMD: 0·31 kg, 95 % CI -0·31, 1·94; P = 0·703, I2 = 0 %) and waist-to-hip ratio (WMD: 0, 95 % CI -0·01, 0·02; P = 0·676, I2 = 0 %). Subgroup analyses based on trial duration, BR or nitrate dose, study design, baseline BMI and athletic status (athlete v. non-athlete) demonstrated similar results. Certainty of evidence across outcomes ranged from low to moderate. This meta-analysis study suggests that BR or nitrate supplements cannot efficiently ameliorate body composition indices regardless of supplement dosage, trial duration and athletic status.

Gastrointestinal, Liver, Pancreas, Oral and Psychological Long-term Symptoms of COVID-19 After Recovery: A Review.

Due to the importance of control and prevention of COVID-19-correlated long-term symptoms, the present review article has summarized what has been currently known regarding the molecular and cellular mechanisms linking COVID-19 to important long-term complications including psychological complications, liver and gastrointestinal manifestations, oral signs as well as even diabetes. COVID-19 can directly affect the body cells through their Angiotensin-converting enzyme 2 (ACE-2) to induce inflammatory responses and cytokine storm. The cytokines cause the release of reactive oxygen species (ROS) and subsequently initiate and promote cell injuries. Another way, COVID-19-associated dysbiosis may be involved in GI pathogenesis. In addition, SARS-CoV-2 reduces butyrate-secreting bacteria and leads to the induction of hyperinflammation. Moreover, SARS-CoV-2-mediated endoplasmic reticulum stress induces de novo lipogenesis in hepatocytes, which leads to hepatic steatosis and inhibits autophagy via increasing mTOR. In pancreas tissue, the virus damages beta-cells and impairs insulin secretion. SARS-COV-2 may change the ACE2 activity by modifying ANGII levels in taste buds which leads to gustatory dysfunction. SARS-CoV-2 infection and its resulting stress can lead to severe inflammation that can subsequently alter neurotransmitter signals. This, in turn, negatively affects the structure of neurons and leads to mood and anxiety disorders. In conclusion, all the pathways mentioned earlier can play a crucial role in the disease's pathogenesis and related comorbidities. However, more studies are needed to clarify the underlying mechanism of the pathogenesis of the new coming virus.

Ameliorative impacts of polymeric and metallic nanoparticles on cisplatin-induced nephrotoxicity: a 2011-2022 review.

Cisplatin (CDDP) is a well-known platinum-based drug used in the treatment of various malignancies. However, the widespread side effects that this drug leaves on normal tissues make its use limited. Since cisplatin is mainly eliminated from the kidneys, CDDP-induced nephrotoxicity is the most significant dose-limiting complication attributed to cisplatin, which often leads to dose withdrawal. Considering the high efficiency of cisplatin in chemotherapy, finding renoprotective drug delivery systems for this drug is a necessity. In this regard, we can take advantages of different nanoparticle-based approaches to deliver cisplatin into tumors either using passive targeting or using specific receptors. In an effort to find more effective cisplatin-based nano-drugs with less nephrotoxic effect, the current 2011-2022 review study was conducted to investigate some of the nanotechnology-based methods that have successfully been able to mitigate CDDP-induced nephrotoxicity. Accordingly, although cisplatin can cause renal failures through inducing mitochondria dysfunction, oxidative stress, lipid peroxidation and endoplasmic reticulum stress, some CDDP-based nano-carriers have been able to reverse a wide range of these advert effects. Based on the obtained results, it was found that the use of different metallic and polymeric nanoparticles can help renal cells to strengthen their antioxidant systems and stay alive through reducing CDDP-induced ROS generation, inhibiting apoptosis-related pathways and maintaining the integrity of the mitochondrial membrane. For example, nanocurcumin could inhibit oxidative stress and acting as a ROS scavenger. CONPs could reduce lipid peroxidation and pro-inflammatory cytokines. CDDP-loaded silver nanoparticles (AgNPs) could inhibit mitochondria-mediated apoptosis. In addition, tea polyphenol-functionalized SeNPs (Se@TE) NPs could mitigate the increased level of dephosphorylated AKT, phosphorylated p38 MAPK and phosphorylated c-Jun N-terminal kinase (JNK) induced by cisplatin. Moreover, exosomes mitigated cisplatin-induced renal damage through inhibiting Bcl2 and increasing Bim, Bid, Bax, cleaved caspase-9, and cleaved caspase-3. Hence, nanoparticle-based techniques are promising drug delivery systems for cisplatin so that some of them, such as lipoplatins and nanocurcumins, have even reached phases 1-3 trials.

Renal, cardiac, neurological, cutaneous and coagulopathic long-term manifestations of COVID-19 after recovery; A review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the novel global coronavirus disease 2019 (COVID-19) disease outbreak. Its pathogenesis is mostly located in the respiratory tract. However, other organs are also affected. Hence, realising how such a complex disturbance affects patients after recovery is crucial. Regarding the significance of control of COVID-19-related complications after recovery, the current study was designed to review the cellular and molecular mechanisms linking COVID-19 to significant long-term signs including renal and cardiac complications, cutaneous and neurological manifestations, as well as blood coagulation disorders. This virus can directly influence on the cells through Angiotensin converting enzyme 2 (ACE-2) to induce cytokine storm. Acute release of Interleukin-1 (IL1), IL6 and plasminogen activator inhibitor 1 (PAI-1) have been related to elevating risk of heart failure. Also, inflammatory cytokines like IL-8 and Tumour necrosis factor-α cause the secretion of von Willebrand factor (VWF) from human endothelial cells and then VWF binds to Neutrophil extracellular traps to induce thrombosis. On the other hand, the virus can damage the blood-brain barrier by increasing its permeability and subsequently enters into the central nervous system and the systemic circulation. Furthermore, SARS-induced ACE2-deficiency decreases [des-Arg9]-bradykinin (desArg9-BK) degradation in kidneys to induce inflammation, thrombotic problems, fibrosis and necrosis. Notably, the angiotensin II-angiotensin II type 1 receptor binding causes an increase in aldosterone and mineralocorticoid receptors on the surface of dendritic cells cells, leading to recalling macrophage and monocyte into inflammatory sites of skin. In conclusions, all the pathways play a key role in the pathogenesis of these disturbances. Nevertheless, more investigations are necessary to determine more pathogenetic mechanisms of the virus.