New insights into the interplay between autophagy, gut microbiota and insulin resistance in metabolic syndrome.

Metabolic syndrome (MetS) is a widespread and multifactorial disorder, and the study of its pathogenesis and treatment remains challenging. Autophagy, an intracellular degradation system that maintains cellular renewal and homeostasis, is essential for maintaining antimicrobial defense, preserving epithelial barrier integrity, promoting mucosal immune response, maintaining intestinal homeostasis, and regulating gut microbiota and microbial metabolites. Dysfunctional autophagy is implicated in the pathological mechanisms of MetS, involving insulin resistance (IR), chronic inflammation, oxidative stress, and endoplasmic reticulum (ER) stress, with IR being a predominant feature. The study of autophagy represents a valuable field of research with significant clinical implications for identifying autophagy-related signals, pathways, mechanisms, and treatment options for MetS. Given the multifactorial etiology and various potential risk factors, it is imperative to explore the interplay between autophagy and gut microbiota in MetS more thoroughly. This will facilitate the elucidation of new mechanisms underlying the crosstalk among autophagy, gut microbiota, and MetS, thereby providing new insights into the diagnosis and treatment of MetS.

[Component profile analysis of Sanhan Huashi Formula based on UHPLC-LTQ-Orbitrap-MS, GC-MS, and UHPLC-QQQ-MS/MS].

This study comprehensively analyzed the active components of Sanhan Huashi Formula using qualitative and quantitative mass spectrometry techniques, laying the foundation for understanding its pharmacological substance basis. UHPLC-LTQ-Orbitrap-MS and GC-MS technologies were used to analyze and identify the volatile and non-volatile components in Sanhan Huashi Formula. UHPLC-QQQ-MS/MS technology was used to simultaneously determine the content of 27 major active components in the formula. The results showed that 308 major chemical components were identified in Sanhan Huashi Formula, among which 60 compounds were identified by comparing with reference standards, mainly including alkaloids, flavonoids, coumarins, triterpenoid saponins, amino acids, and nucleosides. GC-MS technology preliminarily identified 52 volatile compounds, with γ-eudesmol and ß-eudesmol as the main components. The quantitative results demonstrated good linearity(r>0.99) for the 27 active components, indicating the stability, simplicity, and reliability of the established method. Among them, amygdalin, nodakenin, arecoline, ephedrine, and pseudoephedrine had relatively high content and were presumably the main pharmacologically active substances. In conclusion, this study systematically and comprehensively characterized the major chemical components and patterns in Sanhan Huashi Formula, providing a basis for understanding its pharmacological mechanisms and clinical applications.

[Component identification and analysis in vivo of Sanhan Huashi formula].

Sanhan Huashi formula(SHF) is the intermediate of a newly approved traditional Chinese medicine(TCM) Sanhan Huashi Granules for the treatment of COVID-19 infection. The chemical composition of SHF is complex since it contains 20 single herbal medicines. In this study, UHPLC-Orbitrap Exploris 240 was used to identify the chemical components in SHF and in rat plasma, lung and feces after oral administration of SHF, and heat map was plotted for characterizing the distribution of the chemical components. Chromatographic separation was conducted on a Waters ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 µm) using 0.1% formic acid(A)-acetonitrile(B) as mobile phases in a gradient elution. Electrospray ionization(ESI) source was used to acquire data in positive and negative mode. By reference to quasi-molecular ions and MS/MS fragment ions and in combination with MS spectra of reference substances and compound information in literature reports, 80 components were identified in SHF, including 14 flavonoids, 13 coumarins, 5 lignans, 12 amino-compounds, 6 terpenes and 30 other compounds; 40 chemical components were identified in rat plasma, 27 in lung and 56 in feces. Component identification and characterization of SHF in vitro and in vivo lay foundations for disclosure of its pharmacodynamic substances and elucidation of the scientific connotation.

Efficacy and safety of traditional Chinese medicines combined with conventional Western medicines in the treatment of type 2 diabetes mellitus: a network meta-analysis of randomized controlled trials.

Aims/hypothesis: Through a comprehensive analysis of the clinical randomized controlled trials of traditional Chinese medicine (TCM) combined with conventional western medicine (CWM) in treating type 2 diabetes(T2DM) in the past ten years, the clinical efficacy and safety of different TCMs combined with CWM were explored. This study aimed to provide specific suggestions for clinical guidance on treating T2DM. Methods: A literature search was conducted in CNKI, WanFang, VIP, CBM, PubMed, Embase, and Web of Science. The search time was limited from 2010 to the present time. The literature type was a controlled clinical trial study of TCM combined with CWM intervention in treating T2DM. The outcome indices of the efficacy evaluation included fasting blood glucose (FBG), 2-hour postprandial blood glucose (2hPG), glycosylated hemoglobin (HbA1c), adverse reactions, and clinical efficacy. Stata 15 and RevMan 5.4 software were used to conduct a network meta-analysis and a traditional meta-analysis. Results: The results showed that shenqi jiangtang granule combined with sulfonylurea, shenqi jiangtang granules combined with metformin and jinlida granules combined with insulin had significant effects on reductions in FBG, 2hPG and clinical efficacy compared with western medicines alone, which included fasting blood glucose [MD=-2.17, 95%CI=(-2.50, -1.85)], blood sugar at 2 hours after a meal [MD=-1.94, 95%CI=(-2.23, -1.65)], and clinical curative effect [OR= 1.73, 95%CI=(0.59, 2.87)]. Conclusions: TCM combined with CWM has a very significant effect on treating T2DM compared with CWM alone. According to the network meta-analysis, the best intervention measures of different TCMs for different outcome indicators were obtained. Systematic review registration: identifier 42022350372.

Exploration of the mechanisms underlying the beneficial effect of Luo Tong formula on retinal function in diabetic rats via the "gut microbiota-inflammation-retina" axis.

BACKGROUND: Diabetic retinopathy (DR) is a common microvascular complication of diabetes. Luo Tong formula (LTF), a classical traditional Chinese medicine (TCM) prescription, consists of four plants that have been widely and effectively used to treat DR. Previous work in our laboratory has confirmed that LTF can effectively ameliorate DR. However, the potential mechanism underlying the therapeutic effect of LTF on DR has not been fully elucidated. To explore the potential mechanism of action through which LTF prevents and alleviates DR from an inflammation and gut microbiota perspective. MATERIALS AND METHODS: Metabolite profiling of LTF was performed using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). Type 1 diabetes was induced in male Sprague Dawley (SD) rats via tail vein injection of 45 mg/kg streptozotocin. Next, 100 SD rats were randomly divided into four groups, normal control; diabetic control; diabetic + insulin + calcium dobesilate; and diabetic + insulin + LTF. After 12 weeks of treatment, glucose metabolism, fundus oculi, blood-retinal barrier permeability, retinal thickness, microvascular damage, as well as cell junction expression in retinas were measured and the changes observed in different groups were compared. Finally, the alteration in gut microbiota and inflammatory cytokine expression in serum and tissues were monitored, and their correlation was analyzed. RESULTS: A total of 1024 valid peaks were obtained for LTF using GC-MS. The HbA1c and fasting blood glucose (FBG) levels in the LTF group were slightly decreased. LTF exerted protective effects on fundus oculi and the retina structure to different degrees. LTF attenuated systemic and local retinal inflammation by significantly decreasing the levels of seven pro-inflammatory cytokines, including ICAM-1, IL-6, IL-8, MCP-1, VCAM-1, VEGF, and IL-1ß. LTF restored the intestinal microbiota of diabetic rats to levels that were similar to those of normal rats. Further analysis revealed that Enterobacteriales, Prevotellaceae, Enterobacteriaceae, Bacteroides, and Klebsiella were significantly and positively correlated with the inflammatory factors in DR after LTF treatment. CONCLUSIONS: Our results revealed the mechanisms underlying the preventive effects of LTF on DR development and progression. LTF inhibited pathological changes in retinal histopathology, cell composition, and cell junction proteins while effectively ameliorating systemic and local retinal inflammation via regulating pivotal gut microbiota.

Key regulators of intestinal stem cells: diet, microbiota, and microbial metabolites.

Interactions between diet and the intestinal microbiome play an important role in human health and disease development. It is well known that such interactions, whether direct or indirect, trigger a series of metabolic reactions in the body. Evidence suggests that intestinal stem cells (ISCs), which are phenotypic precursors of various intestinal epithelial cells, play a significant role in the regulation of intestinal barrier function and homeostasis. The advent and evolution of intestinal organoid culture techniques have presented a key opportunity to study the association between the intestinal microenvironment and ISCs. As a result, the effects exerted by dietary factors, intestinal microbiomes, and their metabolites on the metabolic regulation of ISCs and the potential mechanisms underlying such effects are being gradually revealed. This review summarises the effects of different dietary patterns on the behaviour and functioning of ISCs and focuses on the crosstalk between intestinal microbiota, related metabolites, and ISCs, with the aim of fully understanding the relationship between these three factors and providing further insights into the complex mechanisms associated with ISCs in the human body. Gaining an understanding of these mechanisms may lead to the development of novel dietary interventions or drugs conducive to intestinal health.

Effectiveness and safety analysis of SanHanHuaShi granules for the treatment of coronavirus disease 2019: Study protocol and statistical analysis plan for a randomized, parallel-controlled, open-label clinical trial.

Background: Coronavirus disease 2019 (COVID-19) was declared a global pandemic in March 2020 by the World Health Organization (WHO). As of July 2, 2022, COVID-19 has caused more than 545 million infections and 6.3 million deaths worldwide, posing a significant threat to human health. Currently, there is still a lack of effective prevention and control strategies for the variation and transmission of SARS-CoV-2. Traditional Chinese medicine (TCM), which has a unique theoretical system, has treated various conditions for thousands of years. Importantly, recent studies have revealed that TCM contributed significantly to COVID-19. SanHanHuaShi (SHHS) granules, a Chinese herbal medicine, which has been included in Protocol for the Diagnosis and Treatment of Novel Coronavirus Disease 2019 (6th to 9th editions) issued by the National Health Commission of China and used to prevent and treat COVID-19 disease. A previous retrospective cohort study showed that SHHS could significantly reduce the severity of mild and moderate COVID-19. However, there is an absence of high-quality randomized controlled clinical studies to confirm the clinical effectiveness of SHHS. Therefore, a clinical study protocol and a statistical analysis plan were designed to investigate the efficacy and safety of SHHS for the prevention and treatment of COVID-19. This study will increase the integrity and data transparency of the clinical research process, which is of great significance for improving the practical application of SHHS granules in the future. Methods and analysis: The study was designed as a 7-day, randomized, parallel controlled, open-label, noninferiority clinical trial of positive drugs. A total of 240 patients with mild and moderate COVID-19 will be enrolled and randomly assigned to receive SanHanHuaShi granules or LianHuaQingWen granules treatment in a 1:1 ratio. Disease classification, vital signs, SARS-CoV-2 nucleic acid testing, symptoms, medications, adverse events, and safety evaluations will be recorded at each visit. The primary outcome will be the clinical symptom recovery rate. Secondary outcomes will include the recovery time of clinical symptoms, negative conversion time of SARS-CoV-2 nucleic acid test negative conversion rate, hospitalization time, antipyretic time, rate of conversion to severe patients, and time and rate of single symptom recovery. Adverse incidents and safety assessments will be documented. All data will be analyzed using a predetermined statistical analysis plan, including our method for imputation of missing data, primary and secondary outcome analyses, and safety outcomes. Discussion: The results of this study will provide robust evidence to confirm the effectiveness and safety of SHHS in the treatment of COVID-19. Clinical Trial Registration: http://www.chictr.org.cn. Trial number: ChiCTR2200058080. Registered on 29 March 2022.

Microbial characteristics across different tongue coating types in a healthy population.

Background The physical appearance of tongue coatings is vital for traditional Chinese medicine (TCM) to diagnose health and disease status. The microbiota of different tongue coatings could also influence coating formation and be further associated with specific diseases. Previous studies have focused on bacteria from different tongue coatings in the context of specific diseases, but the normal variations in healthy individuals remain unknown.Aim: We examined the tongue microbiota by metagenomics in 94 healthy individuals classified into eight different tongue types.Results: The overall composition of the tongue coating microbiome is not drastically different among different coating types, similar to the findings of previous studies in healthy populations. Further analysis revealed microbiota characteristics of each coating type, and many of the key bacteria are reported to be implicated in diseases. Moreover, further inclusion of diabetic patients revealed disease-specific enrichment of Capnocytophaga, even though the same tongue coatings were studied.Conclusions: This work revealed the characteristic compositions of distinctive tongue coatings in a healthy population, which serves as a basis for understanding the tongue coating formation mechanism and provides a valuable reference to further investigate disease-specific tongue coating bacterial markers.