Effectiveness and safety of Arecae Semen compounds for patients with depression: a systematic review and meta-analysis.

BACKGROUND: Arecae Semen is a traditional herbal medicine widely used in the medical service and food industry, but in recent years, the carcinogenesis of edible Arecae Semen chewing has aroused comprehensive attention, therefore it is necessary to evaluate its medicinal properties. Increasing evidence has shown that Arecae Semen Compounds (ASC) possess antidepressant ability. This study aimed to evaluate the effectiveness and safety of ASC in the treatment of depression. METHODS: We retrieved articles in eight databases from their inception to May 2024. Randomized controlled trials (RCTs) comparing the effects of ASC alone or combined with routine treatment in patients with depression were identified. The Cochrane risk of bias (ROB) tool (ROB 2) was used for assessing the ROB in the included trials. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the certainty of the evidence for the review outcomes. The outcomes included Hamilton depression rating scale (HAMD) scores, depression-related symptoms, serum dopamine levels, and adverse events. Stata 14.0 was used for data analysis calculating standardized mean difference (SMD) for continuous outcomes and relative risk (RR) for binary outcomes, both with 95% confidence intervals (CI). RESULTS: Nine RCTs involving 787 patients were included in this review. ASC lowered HAMD scores (SMD - 3.43, 95% CI - 5.24 to - 1.61; I2 = 95.2%, P < 0.001), alleviated depression-related symptoms, increased serum dopamine levels, and reduced the incidence of adverse events slightly (RR 0.18, 95% CI 0.04 to 0.77; I2 = 0, P = 0.775) compared with the control group. Publication bias might account for the asymmetrical presentation of funnel plots. Meta-regression analysis revealed that regarding HAMD scores, there was no significant relationship with duration, sample size, or treatment strategy. The evidence of the outcomes was of very low certainty. CONCLUSIONS: ASC may achieve better therapeutic effects, alleviate depression-related symptoms with a lower incidence of adverse events, and provide a potentially effective and safe complementary therapy for patients with depression. However, the evidence is very uncertain so further researches are required to validate our results and explore clinical implications of Arecae Semen in depth. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022361150.

Licoricesaponin G2 ameliorates bleomycin-induced pulmonary fibrosis via targeting TNF-α signaling pathway and inhibiting the epithelial-mesenchymal transition.

Background: Pulmonary fibrosis (PF) emerges as a significant pulmonary sequelae in the convalescent phase of coronavirus disease 2019 (COVID-19), with current strategies neither specifically preventive nor therapeutic. Licoricesaponin G2 (LG2) displays a spectrum of natural activities, including antibacterial, anti-inflammatory, and antioxidant properties, and has been effectively used in treating various respiratory conditions. However, the potential protective effects of LG2 against PF remain underexplored. Methods: Network analysis and molecular docking were conducted in combination to identify the core targets and pathways through which LG2 acts against PF. In the model of bleomycin (BLM)-induced C57 mice and transforming growth factor-ß1 (TGF-ß1)-induced A549 and MRC5 cells, techniques such as western blot (WB), quantitative Real-Time PCR (qPCR), Immunohistochemistry (IHC), Immunofluorescence (IF), and Transwell migration assays were utilized to analyze the expression of Epithelial-mesenchymal transition (EMT) and inflammation proteins. Based on the analysis above, we identified targets and potential mechanisms underlying LG2's effects against PF. Results: Network analysis has suggested that the mechanism by which LG2 combats PF may involve the TNF-α pathway. Molecular docking studies have demonstrated a high binding affinity of LG2 to TNF-α and MMP9. Observations from the study indicated that LG2 may mitigate PF by modulating EMT and extracellular matrix (ECM) remodeling. It is proposed that the therapeutic effect is likely arises from the inhibition of inflammatory expression through regulation of the TNF-α pathway. Conclusion: LG2 mitigates PF by suppressing TNF-α signaling pathway activation, modulating EMT, and remodeling the ECM. These results provide compelling evidence supporting the use of LG2 as a potential natural therapeutic agent for PF in clinical trials.

Hirudin delays the progression of diabetic kidney disease by inhibiting glomerular endothelial cell migration and abnormal angiogenesis.

BACKGROUND: In the early stages of diabetic kidney disease (DKD), the pathogenesis involves abnormal angiogenesis in the glomerulus. Hirudin, as a natural specific inhibitor of thrombin, has been shown in previous studies to inhibit the migration of various tumor endothelial cells and abnormal angiogenesis. However, its role in DKD remains unclear. METHODS: The effects of hirudin in DKD were studied using spontaneous type 2 diabetic db/db mice (which develop kidney damage at 8 weeks). Network pharmacology was utilized to identify relevant targets. An in vitro high glucose model was established using mouse glomerular endothelial cells (MGECs) to investigate the effects of hirudin on the migration and angiogenic capacity of MGECs. RESULTS: Hirudin can ameliorate kidney damage in db/db mice. Network pharmacology suggests its potential association with the VEGFA/VEGFR2 pathway. Western blot and immunohistochemistry demonstrated elevated protein expression levels of VEGFA, VEGFR2, AQP1, and CD31 in db/db mice, while hirudin treatment reduced their expression. In the MGECs high glucose model, hirudin may reverse the enhanced migration and angiogenic capacity of MGECs in a high glucose environment by altering the expression of VEGFA, VEGFR2, AQP1, and CD31. Moreover, the drug effect gradually increases with higher concentrations of hirudin. CONCLUSIONS: This study suggests that hirudin can improve early-stage diabetic kidney disease kidney damage by inhibiting the migration and angiogenesis of glomerular endothelial cells, thereby further expanding the application scope of hirudin. Additionally, the study found increased expression of AQP1 in DKD, providing a new perspective for further research on the potential pathogenesis of DKD.

Dilemmas in Elderly Diabetes and Clinical Practice Involving Traditional Chinese Medicine.

Diabetes is a widespread chronic disease that occurs mainly in the elderly population. Due to the difference in pathophysiology between elderly and young patients, the current clinical practice to treat elderly patients with anti-diabetes medications still faces some challenges and dilemmas, such as the urgent need for early diagnosis and prevention, and an imbalance between restricted dietary intake and the risk of undernutrition. Traditional Chinese medicine (TCM) offers various treatment regimens that are actively utilized in the field of diabetes management. Through multiple targets and multiple pathways, TCM formulas, medicinal herbs, and active natural products enhance the efficacy of diabetes prevention and diabetes control measures, simplify complex medication management, and improve common symptoms and common diabetic complications in elderly people. Historically, natural products have played a key role in material composition analysis of TCM and mechanism interpretation to enable drug discovery. However, there have been few conclusions on this topic. This review summarizes the development of TCM for the prevention and management of diabetes in elderly people, existing evidence-based clinical practices, and prospects for future development.

Podocyte programmed cell death in diabetic kidney disease: Molecular mechanisms and therapeutic prospects.

Diabetic kidney disease (DKD) is the primary cause of chronic kidney and end-stage renal disease. Glomerular podocyte loss and death are pathological hallmarks of DKD, and programmed cell death (PCD) in podocytes is crucial in DKD progression. PCD involves apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis. During DKD, PCD in podocytes is severely impacted and primarily characterized by accelerated podocyte apoptosis and suppressed autophagy. These changes lead to a gradual decrease in podocyte numbers, impairing the glomerular filtration barrier function and accelerating DKD progression. However, research on the interactions between the different types of PCD in podocytes is lacking. This review focuses on the novel roles and mechanisms of PCD in the podocytes of patients with DKD. Additionally, we summarize clinical drugs capable of regulating podocyte PCD, present challenges and prospects faced in developing drugs related to podocyte PCD and suggest that future research should further explore the detailed mechanisms of podocyte PCD and interactions among different types of PCD.

Effectiveness and safety of Sanhan Huashi granules versus nirmatrelvir-ritonavir in adult patients with COVID-19: A randomized, open-label, multicenter trial.

Sanhan Huashi granules (SHG) demonstrated therapeutic effects against coronavirus disease 2019 (COVID-19) in observational studies. In order to compare the effectiveness and safety of SHG and nirmatrelvir-ritonavir in treating adults with mild-to-moderate COVID-19, we conducted a randomized, active-controlled, open-label, multi-center trial conducted between February and July in 2023. The patients were randomized in a 1:1 ratio to the SHG group and the nirmatrelvir-ritonavir group. A total of 400 participants were randomized, among which 200 participants ultimately received SHG and 198 received nirmatrelvir-ritonavir. The primary outcome was time to sustained clinical recovery through day 28. SHG significantly shortened the median time to sustained clinical recovery compared to nirmatrelvir-ritonavir (6.0 (95% CI, 5.0 to 6.0) vs. 8.0 (95% CI, 6.0 to 9.0) d; P = 0.001), particularly for individual symptoms including fever, sore throat, cough and fatigue. No participants in either group died and incidence of severe COVID-19 showed no difference between two groups. Participants who received nirmatrelvir-ritonavir demonstrated a higher rate of virus clearance on day 5 compared to those received SHG (46.4% (95% CI, 39.1 to 53.7) vs. 65.6% (95% CI, 58.3 to 72.4); P < 0.001). Most adverse events were mild in both groups. In summary, SHG was superior to nirmatrelvir-ritonavir in shortening the time to sustained clinical recovery in participants with mild-to-moderate COVID-19, despite a lower virus clearance rate observed after 5 d of treatment (Chinese Clinical Trial Registry Identifier: ChiCTR2300067872).

The 100 top-cited articles in menopausal syndrome: a bibliometric analysis.

BACKGROUND: Significant scientific research has been conducted concerning menopausal syndrome(MPS), yet few bibliometric analyses have been performed. Our aim was to recognise the 100 most highly cited published articles on MPS and to analytically evaluate their key features. METHODS: To identify the 100 most frequently cited articles, a search was conducted on Web of Science using the term 'menopausal syndrome'. Articles that matched the predetermined criteria were scrutinised to obtain the following data: citation ranking, year of publication, publishing journal, journal impact factor, country of origin, academic institution, authors, study type, and keywords. RESULTS: The publication period is from January 1, 2000, to August 31, 2022. The maximum number of citations was 406 and in 2012. The median citations per year was 39.70. Most of the articles focused on treatment and complications. These articles were published in 36 different journals, with the Journal of MENOPAUSE having published the greatest number (14%). Forty-eight articles (48%) were from the United States, with the University of Pittsburgh being the leading institute (9%). Joann E. Manson was the most frequent first author (n = 6). Observational studies were the most frequently conducted research type (n = 53), followed by experimental studies (n = 33). Keyword analysis identified classic research topics, including genitourinary syndrome of menopause, bone mineral density (BMD), and anti-mullerian hormone (AMH) loci. CONCLUSION: Using bibliometrics, we conducted an analysis to identify the inadequacies, traditional focal points, and potential prospects in the study of MPS across current scientific areas. Treatment and complications are at the core of MPS research, whereas prediction and biomarkers have less literature of high quality. There is a necessity for innovative analytical metrics to measure the real effect of these papers with a high level of citation on clinical application.

LiverRisk score: An accurate, cost-effective tool to predict fibrosis, liver-related, and diabetes-related mortality in the general population.

BACKGROUND: Noninvasive and early assessment of liver fibrosis is of great significance and is challenging. We aimed to evaluate the predictive performance and cost-effectiveness of the LiverRisk score for liver fibrosis and liver-related and diabetes-related mortality in the general population. METHODS: The general population from the NHANES 2017-March 2020, NHANES 1999-2018, and UK Biobank 2006-2010 were included in the cross-sectional cohort (n = 3,770), along with the NHANES follow-up cohort (n = 25,317) and the UK Biobank follow-up cohort (n = 17,259). The cost-effectiveness analysis was performed using TreeAge Pro software. Liver stiffness measurements ≥10 kPa were defined as compensated advanced chronic liver disease (cACLD). FINDINGS: Compared to conventional scores, the LiverRisk score had significantly better accuracy and calibration in predicting liver fibrosis, with an area under the receiver operating characteristic curve (AUC) of 0.76 (0.72-0.79) for cACLD. According to the updated thresholds of LiverRisk score (6 and 10), we reclassified the population into three groups: low, medium, and high risk. The AUCs of LiverRisk score for predicting liver-related and diabetes-related mortality at 5, 10, and 15 years were all above 0.8, with better performance than the Fibrosis-4 score. Furthermore, compared to the low-risk group, the medium-risk and high-risk groups in the two follow-up cohorts had a significantly higher risk of liver-related and diabetes-related mortality. Finally, the cost-effectiveness analysis showed that the incremental cost-effectiveness ratio for LiverRisk score compared to FIB-4 was USD $18,170 per additional quality-adjusted life-year (QALY) gained, below the willingness-to-pay threshold of $50,000/QALY. CONCLUSIONS: The LiverRisk score is an accurate, cost-effective tool to predict liver fibrosis and liver-related and diabetes-related mortality in the general population. FUNDING: The National Natural Science Foundation of China (nos. 82330060, 92059202, and 92359304); the Key Research and Development Program of Jiangsu Province (BE2023767a); the Fundamental Research Fund of Southeast University (3290002303A2); Changjiang Scholars Talent Cultivation Project of Zhongda Hospital of Southeast University (2023YJXYYRCPY03); and the Research Personnel Cultivation Program of Zhongda Hospital Southeast University (CZXM-GSP-RC125).

Mechanism of traditional Chinese medicine in elderly diabetes mellitus and a systematic review of its clinical application.

Objective: Affected by aging, the elderly diabetes patients have many pathological characteristics different from the young people, including more complications, vascular aging, cognitive impairment, osteoporosis, and sarcopenia. This article will explore their pathogenesis and the mechanism of Traditional Chinese medicine (TCM) intervention, and use the method of systematic review to evaluate the clinical application of TCM in elderly diabetes. Method: Searching for randomized controlled trials (RCTs) published from January 2000 to November 2023 in the following databases: Web of Science, Pubmed, Embase, Cochrane Library, Sinomed, China National Knowledge Internet, Wanfang and VIP. They were evaluated by three subgroups of Traditional Chinese Prescription, Traditional Chinese patent medicines and Traditional Chinese medicine extracts for their common prescriptions, drugs, adverse reactions and the quality of them. Results and Conclusion: TCM has the advantages of multi-target and synergistic treatment in the treatment of elderly diabetes. However, current clinical researches have shortcomings including the inclusion of age criteria and diagnosis of subjects are unclear, imprecise research design, non-standard intervention measures, and its safety needs further exploration. In the future, the diagnosis of elderly people with diabetes needs to be further clarified. Traditional Chinese patent medicines included in the pharmacopoeia can be used to conduct more rigorous RCTs, and then gradually standardize the traditional Chinese medicine prescriptions and traditional Chinese medicine extracts, providing higher level evidence for the treatment of elderly diabetes with traditional Chinese medicine.

Double-blinded, randomized clinical trial of Gegen Qinlian decoction pinpoints Faecalibacterium as key gut bacteria in alleviating hyperglycemia.

Background: Accumulating evidence suggests that metabolic disorders, including type 2 diabetes mellitus (T2DM), can be treated with traditional Chinese medicine formulas, such as the Gegen Qinlian decoction (GQD). This study elucidates the mechanisms by which gut microbes mediate the anti-diabetic effects of GQD. Methods: We conducted a double-blind randomized clinical trial involving 120 untreated participants with T2DM. During the 12-week intervention, anthropometric measurements and diabetic traits were recorded every 4 weeks. Fecal microbiota and serum metabolites were measured before and after the intervention using 16S rDNA sequencing, liquid chromatography-mass spectrometry, and Bio-Plex panels. Results: Anti-diabetic effects were observed in the GQD group in the human trial. Specifically, glycated hemoglobin, fasting plasma glucose, and two-hour postprandial blood glucose levels were significantly lower in the GQD group than in the placebo group. Additionally, Faecalibacterium was significantly enriched in the GQD group, and the short-chain fatty acid levels were higher and the serum inflammation-associated marker levels were lower in the GQD group compared to the placebo group. Moreover, Faecalibacterium abundance negatively correlated with the levels of serum hemoglobin, fasting plasma glucose, and pro-inflammatory cytokines. Finally, the diabetes-alleviating effect of Faecalibacterium was confirmed by oral administration of Faecalibacterium prausnitzii (DSMZ 17677) in T2DM mouse model. Conclusions: GQD improved type 2 diabetes primarily by modulating the abundance of Faecalibacterium in the gut microbiota, alleviating metabolic disorders and the inflammatory state. Trial registration: Registry No. ChiCTR-IOR-15006626.

The association between interleukin family and diabetes mellitus and its complications: An overview of systematic reviews and meta-analyses.

OBJECTIVE: To evaluate and summarize the association between interleukin (IL) concentrations and diabetes mellitus (DM) and its complications. METHODS: Meta-analyses and eligible individual studies of observational studies investigating the associations between IL and DM and its complications were included. The random-effects model was used to estimate the summary effect, and the heterogeneity among studies was assessed using the Q-statistic and the I2 metric; The Egger's regression and the χ2 test were used to test for small study effects and excess significance bias. RESULTS: This overview identified 34 meta-analyses that investigated the association between IL concentrations and DM and its complications. Meta-analyses of prospective studies indicated that elevated circulating IL-6 and IL-1ß had predictive value for the incident of type 2 diabetes mellitus (T2DM), type 1 diabetes mellitus (T1DM) as well as gestational diabetes mellitus (GDM), and the overall Hazard Ratio (HR) of T2DM was 1.28 (95 % CI: 1.17, 1.40; P＜0.001) per 1 log pg/ml increment in IL-6 levels, however, there was no correlation between circulating IL-10 levels and DM. Meanwhile, the increased level of IL-6 was significantly associated several diabetic complications (Diabetic kidney disease[DKD], diabetic peripheral neuropathy[DPN], and cognitive impairment[CI]), and for the diabetic retinopathy (DR), the levels of IL-1ß, IL-8 and IL-10 in the aqueous humor and vitreous humor, but not the blood were significantly correlated with it. CONCLUSION: Multiple ILs, such as the IL-6 and IL-1ß, are definitively linked to DM and its complications, and they may be new targets for the diagnosis and treatment, but stronger evidence needs to be confirmed by prospective studies with larger sample sizes and longer observation periods.

Research progress in the construction of animal models of autoimmune thyroiditis.

Autoimmune thyroiditis (AIT), also known as Hashimoto's thyroiditis (HT), is an autoimmune disease that is characterised by elevated thyroid-specific antibody titres. The incidence of AIT is increasing year over year, making it urgent to establish a suitable animal model for this condition, in order to better explore its pathogenesis and potential pharmaceutical mechanisms for treatment. Owing to a lack of basic research on this disease, problems such as disparate modelling methods with unclear and varying success rates make it difficult for researchers to obtain effective information on AIT in the short term. This report summarises and analyzes the current literature on AIT and combines actual operability to explain the selection and specific implementation processes behind the uses of different modelling approaches, to provide a better overall understanding of autoimmune thyroid diseases.

Crosstalk among podocytes, glomerular endothelial cells and mesangial cells in diabetic kidney disease: an updated review.

Diabetic kidney disease (DKD) is a long-term and serious complication of diabetes that affects millions of people worldwide. It is characterized by proteinuria, glomerular damage, and renal fibrosis, leading to end-stage renal disease, and the pathogenesis is complex and involves multiple cellular and molecular mechanisms. Among three kinds of intraglomerular cells including podocytes, glomerular endothelial cells (GECs) and mesangial cells (MCs), the alterations in one cell type can produce changes in the others. The cell-to-cell crosstalk plays a crucial role in maintaining the glomerular filtration barrier (GFB) and homeostasis. In this review, we summarized the recent advances in understanding the pathological changes and interactions of these three types of cells in DKD and then focused on the signaling pathways and factors that mediate the crosstalk, such as angiopoietins, vascular endothelial growth factors, transforming growth factor-ß, Krüppel-like factors, retinoic acid receptor response protein 1 and exosomes, etc. Furthermore, we also simply introduce the application of the latest technologies in studying cell interactions within glomerular cells and new promising mediators for cell crosstalk in DKD. In conclusion, this review provides a comprehensive and updated overview of the glomerular crosstalk in DKD and highlights its importance for the development of novel intervention approaches.

Microbiome and metabolome dysbiosis analysis in impaired glucose tolerance for the prediction of progression to diabetes mellitus.

Gut microbiota and circulating metabolite dysbiosis predate important pathological changes in glucose metabolic disorders; however, comprehensive studies on impaired glucose tolerance (IGT), a diabetes mellitus (DM) precursor, are lacking. Here, we perform metagenomic sequencing and metabolomics on 47 pairs of individuals with IGT and newly diagnosed DM and 46 controls with normal glucose tolerance (NGT); patients with IGT are followed up after 4 years for progression to DM. Analysis of baseline data reveals significant differences in gut microbiota and serum metabolites among the IGT, DM, and NGT groups. In addition, 13 types of gut microbiota and 17 types of circulating metabolites showed significant differences at baseline before IGT progressed to DM, including higher levels of Eggerthella unclassified, Coprobacillus unclassified, Clostridium ramosum, L-valine, L-norleucine, and L-isoleucine, and lower levels of Eubacterium eligens, Bacteroides faecis, Lachnospiraceae bacterium 3_1_46FAA, Alistipes senegalensis, Megaspaera elsdenii, Clostridium perfringens, α-linolenic acid, 10E,12Z-octadecadienoic acid, and dodecanoic acid. A random forest model based on differential intestinal microbiota and circulating metabolites can predict the progression from IGT to DM (AUC = 0.87). These results suggest that microbiome and metabolome dysbiosis occur in individuals with IGT and have important predictive values and potential for intervention in preventing IGT from progressing to DM.

Multiomics Analyses With Stool-Type Stratification in Patient Cohorts and Blautia Identification as a Potential Bacterial Modulator in Type 2 Diabetes Mellitus.

Heterogeneity in host and gut microbiota hampers microbial precision intervention of type 2 diabetes mellitus (T2DM). Here, we investigated novel features for patient stratification and bacterial modulators for intervention, using cross-sectional patient cohorts and animal experiments. We collected stool, blood, and urine samples from 103 patients with recent-onset T2DM and 25 healthy control subjects (HCs), performed gut microbial composition and metabolite profiling, and combined it with host transcriptome, metabolome, cytokine, and clinical data. Stool type (dry or loose stool), a feature of the stool microenvironment recently explored in microbiome studies, was used for stratification of patients with T2DM as it explained most of the variation in the multiomics data set among all clinical parameters in our covariate analysis. T2DM with dry stool (DM-DS) and loose stool (DM-LS) were clearly differentiated from HC and each other by LightGBM models, optimal among multiple machine learning models. Compared with DM-DS, DM-LS exhibited discordant gut microbial taxonomic and functional profiles, severe host metabolic disorder, and excessive insulin secretion. Further cross-measurement association analysis linked the differential microbial profiles, in particular Blautia abundances, to T2DM phenotypes in our stratified multiomics data set. Notably, oral supplementation of Blautia to T2DM mice induced inhibitory effects on lipid accumulation, weight gain, and blood glucose elevation with simultaneous modulation of gut bacterial composition, revealing the therapeutic potential of Blautia. Our study highlights the clinical implications of stool microenvironment stratification and Blautia supplementation in T2DM, offering promising prospects for microbial precision treatment of metabolic diseases.

Ginsenoside Rb2 inhibits p300-mediated SF3A2 acetylation at lysine 10 to promote Fscn1 alternative splicing against myocardial ischemic/reperfusion injury.

INTRODUCTION: Ginsenosides (GS) derived from Panax ginseng can regulate protein acetylation to promote mitochondrial function for protecting cardiomyocytes. However, the potential mechanisms of GS for regulating acetylation modification are not yet clear. OBJECTIVES: This study aimed to explore the potential mechanisms of GS in regulating protein acetylation and identify ginsenoside monomer for fighting myocardial ischemia-related diseases. METHODS: The 4D-lable free acetylomic analysis was employed to gain the acetylated proteins regulated by GS pretreatment. The co-immunoprecipitation assay, immunofluorescent staining, and mitochondrial respiration measurement were performed to detect the effect of GS or ginsenoside monomer on acetylated protein level and mitochondrial function. RNA sequencing, site-specific mutation, and shRNA interference were used to explore the downstream targets of acetylation modificationby GS. Cellular thermal shift assay and surface plasmon resonance were used for identifying the binding of ginsenoside with target protein. RESULTS: In the cardiomyocytes of normal, oxygen glucose deprivation and/or reperfusion conditions, the acetylomic analysis identified that the acetylated levels of spliceosome proteins were inhibited by GS pretreatment and SF3A2 acetylation at lysine 10 (K10) was significantly decreased as a potential target of GS. Ginsenoside Rb2 was identified as one of the active ginsenoside monomers for reducing the acetylation of SF3A2 (K10), which enhanced mitochondrial respiration against myocardial ischemic injury in in vivo and in vitro experiments. RNA-seq analysis showed that ginsenoside Rb2 promoted alternative splicing of mitochondrial function-related genes and the level of fascin actin-bundling protein 1 (Fscn1) was obviously upregulated, which was dependent on SF3A2 acetylation. Critically, thermodynamic, kinetic and enzymatic experiments demonstrated that ginsenoside Rb2 directly interacted with p300 for inhibiting its activity. CONCLUSION: These findings provide a novel mechanism underlying cardiomyocyte protection of ginsenoside Rb2 by inhibiting p300-mediated SF3A2 acteylation for promoting Fscn1 expression, which might be a promising approach for the prevention and treatment of myocardial ischemic diseases.

Practice and principle of traditional Chinese medicine for the prevention and treatment of COVID-19.

Traditional Chinese medicine (TCM) has played an important role in the prevention and treatment of Coronavirus disease 2019 (COVID-19) epidemic in China. The integration of Chinese and Western medicine is an important feature of Chinese COVID-19 prevention and treatment. According to a series of evidence-based studies, TCM can reduce the infection rate of severe acute respiratory syndrome coronavirus 2 in high-risk groups. For patients with mild and moderate forms of COVID-19, TCM can relieve the related signs and symptoms, shorten the period of nucleic-acid negative conversion, and reduce conversion rate to the severe form of the disease. For COVID-19 patients with severe and critical illnesses, TCM can improve inflammatory indicators and blood oxygen saturation, shorten the hospital stay, and reduce the mortality rate. During recovery, TCM can improve patients' symptoms, promote organ function recovery, boost the quality of patients' life, and reduce the nucleic-acid repositive conversion rate. A series of mechanism research studies revealed that capability of TCM to treat COVID-19 through antiviral and anti-inflammatory effects, immune regulation, and protection of organ function via a multicomponent, multitarget, and multipathway approach.

Common mechanisms underlying diabetic vascular complications: focus on the interaction of metabolic disorders, immuno-inflammation, and endothelial dysfunction.

Diabetic vascular complications (DVCs), including macro- and micro- angiopathy, account for a high percentage of mortality in patients with diabetes mellitus (DM). Endothelial dysfunction is the initial and role step for the pathogenesis of DVCs. Hyperglycemia and lipid metabolism disorders contribute to endothelial dysfunction via direct injury of metabolism products, crosstalk between immunity and inflammation, as well as related interaction network. Although physiological and phenotypic differences support their specified changes in different targeted organs, there are still several common mechanisms underlying DVCs. Also, inhibitors of these common mechanisms may decrease the incidence of DVCs effectively. Thus, this review may provide new insights into the possible measures for the secondary prevention of DM. And we discussed the current limitations of those present preventive measures in DVCs research. Video Abstract.

Natural compounds efficacy in complicated diabetes: A new twist impacting ferroptosis.

Ferroptosis, as a way of cell death, participates in the body's normal physiological and pathological regulation. Recent studies have shown that ferroptosis may damage glucose-stimulated islets ß Insulin secretion and programmed cell death of T2DM target organs are involved in the pathogenesis of T2DM and its complications. Targeting suppression of ferroptosis with specific inhibitors may provide new therapeutic opportunities for previously untreated T2DM and its target organs. Current studies suggest that natural bioactive compounds, which are abundantly available in drugs, foods, and medicinal plants for the treatment of T2DM and its target organs, have recently received significant attention for their various biological activities and minimal toxicity, and that many natural compounds appear to have a significant role in the regulation of ferroptosis in T2DM and its target organs. Therefore, this review summarized the potential treatment strategies of natural compounds as ferroptosis inhibitors to treat T2DM and its complications, providing potential lead compounds and natural phytochemical molecular nuclei for future drug research and development to intervene in ferroptosis in T2DM.