Objective: Myocardial ischemia-reperfusion (I/R) injury is a complex clinical problem that often leads to further myocardial injury. Curcumin is the main component of turmeric, which has been proved to have many cardioprotective effects. However, the cardioprotective potential of curcumin remains unclear. The present systematic review and meta-analysis aimed to evaluate the clinical and preclinical (animal model) evidence regarding the effect of curcumin on myocardial I/R injury. Methods: Eight databases and three register systems were searched from inception to 1 November 2022. Data extraction, study quality assessment, data analyses were carried out strictly. Then a fixed or random-effects model was applied to analyze the outcomes. SYRCLE’s-RoB tool and RoB-2 tool was used to assess the methodological quality of the included studies. RevMan 5.4 software and stata 15.1 software were used for statistical analysis. Results: 24 animal studies, with a total of 503 animals, and four human studies, with a total of 435 patients, were included in this study. The meta-analysis of animal studies demonstrated that compared with the control group, curcumin significantly reduced myocardial infarction size (p < 0.00001), and improved the cardiac function indexes (LVEF, LVFS, LVEDd, and LVESd) (p < 0.01). In addition, the indexes of myocardial injury markers, myocardial oxidation, myocardial apoptosis, inflammation, and other mechanism indicators also showed the beneficial effect of curcumin (p < 0.05). In terms of clinical studies, curcumin reduced the incidence of cardiac dysfunction, myocardial infarction in the hospital and MACE in the short term, which might be related to its anti-inflammatory and anti-oxidative property. Dose-response meta-analysis predicted, 200 mg/kg/d bodyweight was the optimal dose of curcumin in the range of 10–200 mg/kg/d, which was safe and non-toxic according to the existing publications. Conclusion: Our study is the first meta-analysis that includes both preclinical and clinical researches. We suggested that curcumin might play a cardioprotective role in acute myocardial infarction in animal studies, mainly through anti-oxidative, anti-inflammatory, anti-apoptosis, and anti-fibrosis effects. In addition, from the clinical studies, we found that curcumin might need a longer course of treatment and a larger dose to protect the myocardium, and its efficacy is mainly reflected on reducing the incidence of myocardial infarction and MACE. Our finding provides some meaningful advice for the further research.

/pdf/cardioprotective-effects-of-curcumin-against-myocardial-i-r-2h90ublc.pdf

Cardioprotective effects of curcumin against myocardial I/R injury: A systematic review and meta-analysis of preclinical and clinical studies

Epithelial-mesenchymal transition (EMT) plays an important role in interstitial matrix deposition and renal fibrosis in diabetic kidney disease (DKD). It has been verified that Astragaloside IV (AS-IV) is beneficial for ameliorating DKD. However, the underlying mechanisms of AS-IV on regulating EMT in DKD are yet to be established. Accumulated evidence has suggested that C-X3-C motif ligand 1 (CX3CL1) plays a significant role in the progression of EMT.We aimed to investigate whether AS-IV could alleviate EMT by regulating CX3CL1 in DKD and reveal its underlying mechanisms.For the in vivo study, mice were divided into the following five groups (n=10): db/m+vehicle, db/db+vehicle, db/db+AS-IV-L (10mg/kg/d), db/db+AS-IV-M (20mg/kg/d), db/db+AS-IV-H (40mg/kg/d). After 12 weeks of treatment, the renal injuries were assessed based on the related parameters of urine, blood and histopathological examination. Immunohistochemistry and Western blotting were used to detect relative proteins levels. Then in HK-2 cells, the molecular mechanism of AS-IV attenuating the EMT in mice with DKD through the CX3CL1-RAF/MEK/ERK pathway was studied.In the present study, we found that AS-IV reduced urinary protein levels and improved renal pathological damage in DKD mice. Moreover, AS-IV ameliorated the renal tubular EMT induced by hyperglycemia or high glucose (HG), and decreased the expression of CX3CL1 and inhibited the activation of the RAF/MEK/ERK pathway in vivo and in vitro. In HK-2 cells, downregulation of CX3CL1 suppressed the stimulation of the RAF/MEK/ERK pathway and EMT induced by HG. However, CX3CL1 overexpression eliminated the benefits of AS-IV on the RAF/MEK/ERK pathway and EMT.In summary, we indicated that AS-IV alleviates renal tubular EMT through the CX3CL1-RAF/MEK/ERK signaling pathway, indicating that CX3CL1 could be a potential therapeutic target of AS-IV in DKD. 

/pdf/astragaloside-iv-alleviates-renal-tubular-epithelial-12b9n41n.pdf

Astragaloside IV Alleviates Renal Tubular Epithelial-Mesenchymal Transition via CX3CL1-RAF/MEK/ERK Signaling Pathway in Diabetic Kidney Disease

Background: Fibrosis-related diseases (FRD) include cerebral fibrosis, pulmonary fibrosis, cardiac fibrosis, liver fibrosis, renal fibrosis, peritoneal fibrosis, etc. The effects of fibrosis can be severe, resulting in organ dysfunction, functional decline, and even organ failure, which can cause serious health problems. Aim: Currently, there is no effective modern medicine for anti-fibrosis in the clinics; however, Chinese medicine has a certain beneficial effect on treating such diseases. Astragalus Mongholicus (AM) has rich medicinal value, and its anti-fibrosis effect has been recently investigated. In recent years, more and more experimental studies have been conducted on the intervention of astragaloside IV (AS-IV), astragalus polysaccharide (APS), astragalus flavone, cycloastragalus alcohol, astragalus water extract and other pharmacological components in fibrosis-related diseases, attracting the interest of researchers. We aim to provide ideas for future research by summarizing recent research advances of AM in treating fibrosis-related diseases. Methods: A literature search was conducted from the core collections of electronic databases such as Baidu Literature, Sciencen.com, Google Scholar, PubMed, and Science Direct using the above keywords and the pharmacological and phytochemical details of the plant. Results: AM can be used to intervene in fibrosis-disease progression by regulating inflammation, oxidative stress, the immune system, and metabolism. Conclusion: AS-IV, APS, and astragalus flavone were studied and discussed in detail. These components have high potential anti-fibrosis activity. Overall, this review aims to gain insight into the AM’s role in treating fibro-related diseases.

/pdf/astragalus-mongholicus-a-review-of-its-anti-fibrosis-3ufz7ruc.pdf

Astragalus Mongholicus: A review of its anti-fibrosis properties

Therapeutic and delivery strategies of phytoconstituents for renal fibrosis.

Study on active components of mulberry leaf for the prevention and treatment of cardiovascular complications of diabetes

Introduction Second-generation androgen receptor inhibitors (SGARIs), namely enzalutamide, apalutamide, and darolutamide, are good for improving survival outcomes in prostate cancer patients, but some researchers have shown that using SGARIs increases side effects, which complicates clinicians’ choice of. Therefore, we performed this network meta-analysis to assess the efficacy and toxicity of several SGARIs in the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC), non-metastatic castration-resistant prostate cancer (nmCRPC), and metastatic castration-resistant prostate cancer (mCRPC). Methods We searched PubMed, EMBASE and Cochrane Library databases from January 2000 to December 2022 to identify randomized controlled studies associated with SGARIs. We use Stata 16.0 and R 4.4.2 for data analysis, hazard ratio (HR) with 95% confidence intervals (CI) were used to assess the results. Results This meta-analysis included 7 studies with a total of 9488 patients. In mHSPC, enzalutamide and darolutamide had a positive effect on overall survival (OS) (HR, 0.70; 95% CI, 0.59-0.82), but we did not find a difference in their efficacy to improve OS (HR, 1.19; 95% CI, 0.75-1.89). Also in nmCRPC, enzalutamide, apalutamide and darolutamide were beneficial for metastasis-free survival (MFS) (HR, 0.32; 95% CI, 0.25-0.41). Compared to darolutamide, enzalutamide (HR, 0.71; 95% CI, 0.54-0.93) and apalutamide (HR, 0.68; 95% CI, 0.51-0.91) prolonged MFS, but there was no difference in efficacy between enzalutamide and apalutamide (HR, 0.97; 95% CI, 0.73-1.28). Finally in mCRPC, there was no significant difference in indirect effects on OS between pre- and post-chemotherapy enzalutamide (HR, 0.89; 95% CI, 0.70-1.13). However, using enzalutamide before chemotherapy to improve radiographic progression-free survival (rPFS) was a better option (HR, 2.11; 95% CI, 1.62-2.73). Conclusion The SGARIs used in each trial were beneficial for the primary endpoint in the study. Firstly there was no significant difference in the effect of enzalutamide and darolutamide in improving OS in patients with mHSPC. Secondly improving MFS in patients with nmCRPC was best achieved with enzalutamide and apalutamide. In addition both pre- and post-chemotherapy use of enzalutamide was beneficial for OS in mCRPC patients, but for improving rPFS pre-chemotherapy use of enzalutamide should be preferred. The INPLASY registration number of this systematic review is INPLASY202310084.

/pdf/comparative-efficacy-of-second-generation-androgen-receptor-3ax5pkh6.pdf

Comparative efficacy of second-generation androgen receptor inhibitors for treating prostate cancer: A systematic review and network meta-analysis

Introduction Resistin is a small secretory adipokine which is implicated to obesity and associated diseases. Recently, plenty of research papers have been conducted to explore the association between peripheral resistin and the severity of acute pancreatitis (AP). However, the results were controversial. In this study, we aimed to confirm the effect of peripheral resistin and the development of acute pancreatitis. Methods A comprehensive online search was performed using the PubMed, Embase, Web of Science, CNKI, and Wanfang databases up through January 20, 2022. The retrieved records and their references were screened to identify additional studies. Data were extracted to calculate the pooled Hedges' g and its 95% CI, which were selected to assess peripheral resistin levels and the severity of acute pancreatitis. Subgroup analyses, sensitivity analyses, meta-regression, and publication bias tests were also undertaken based on obtained information. Results A total of eleven studies with 892 acute pancreatitis patients were enrolled in the study. Peripheral resistin levels were significantly increased in severe acute pancreatitis compared with mild acute pancreatitis (Hedges' g = 2.092, 95% CI: 0.994–3.190, P < 0.001). Subgroup analyses based on sample types and ethnicity also showed similar results. A single study did not affect our results, which was verified by sensitivity analysis. Meta-regression analyses revealed that age, gender of the included subjects, sample size, and publication year did not moderate effects on the present results. Conclusion In our study, peripheral resistin levels were significantly elevated in patients with severe AP compared with patients with mild AP. Abnormal resistin levels may provide us some new insights in predicting the severity of AP.

/pdf/alteration-of-peripheral-resistin-and-the-severity-of-acute-1o3g4ap8.pdf

Alteration of Peripheral Resistin and the Severity of Acute Pancreatitis: A Meta-Analysis

Renal protective effects of astragaloside IV, in diabetes mellitus kidney damage animal models: A systematic review, meta-analysis

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Comparative efficacy of second-generation androgen receptor inhibitors for treating prostate cancer: A systematic review and network meta-analysis

Alteration of Peripheral Resistin and the Severity of Acute Pancreatitis: A Meta-Analysis

Renal protective effects of astragaloside IV, in diabetes mellitus kidney damage animal models: A systematic review, meta-analysis