Sishen Pill and its active phytochemicals in treating inflammatory bowel disease and colon cancer: an overview.

The incidence of inflammatory bowel disease (IBD) and the associated risk of colon cancer are increasing globally. Traditional Chinese medicine (TCM) treatment has unique advantages. The Sishen Pill, a common Chinese patented drug used to treat abdominal pain and diarrhea, consists mainly of Psoraleae Fructus, Myristicae Semen, Euodiae Fructus, and Schisandra Chinensis. Modern research has confirmed that Sishen Pill and its active secondary metabolites, such as psoralen, myristicin, evodiamine, and schisandrin, can improve intestinal inflammation and exert antitumor pharmacological effects. Common mechanisms in treating IBD and colon cancer mainly include regulating inflammation-related signaling pathways such as nuclear factor-kappa B, mitogen-activated protein kinase, phosphatidylinositol 3-kinase, NOD-like receptor heat protein domain-related protein 3, and wingless-type MMTV integration site family; NF-E2-related factor 2 and hypoxia-inducible factor 1α to inhibit oxidative stress; mitochondrial autophagy and endoplasmic reticulum stress; intestinal immune cell differentiation and function through the Janus kinase/signal transducer and activator of transcription pathway; and improving the gut microbiota and intestinal barrier. Overall, existing evidence suggests the potential of the Sishen pill to improve IBD and suppress inflammation-to-cancer transformation. However, large-scale randomized controlled clinical studies and research on the safety of these clinical applications are urgently required.

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.

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.

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.

Stacking Ensemble of Disproportionality Indicators for Adverse Vaccine Reactions Detection-An Empirical Study on Predicting Adverse Reactions of COVID-19 Vaccines.

Vaccine safety is a critical issue for public health, which has recently become more crucial than ever since COVID-19 started to spread worldwide in 2020. Many COVID-19 vaccines have been developed and used without following the traditional three clinical trial stages. Instead, most COVID-19 vaccines were approved through emergency use approval (EUA) within one year, significantly raising the risk of rare and severe adverse events. Reporting systems like the Vaccine Adverse Event Reporting System (VAERS) have been established worldwide to detect unknown and severe adverse reactions as early as possible. Although experts and researchers have been working hard to find ways to detect adverse vaccine event (AVE) signals from VAERS data, most of the contemporary methods are statistical methods based on measuring the disproportionality between vaccine-induced events and non-vaccine-induced events. This paper proposes a novel ensemble AVE detection method, which adopts a stacking ensemble of various disproportionality indicators, fusing dual-scale contingency values measured in single and cumulative yearly duration, and embraces the concept of feature concatenation. Experiments conducted on US VAERS data to predict AVE caused by COVID-19 vaccines show that our proposed method is effective. We observed that: (1) Stacking ensemble of various disproportionality indicators is superior to any single disproportionality indicator and voting ensemble method; (2) Fusing dual-scale contingency values and feature concatenation brings synergy to our proposed stacking ensemble AVE detection. Compared to the best disproportionality metric in this study, our top-performing ensemble version exhibited a 34% improvement in accuracy, 71% in precision, 29% in recall, and 77% in F-measure, with a slight decrease (8%) in specificity.

Comparison of the effects of different percentages of soy protein in the diet on patients with type 2 diabetic nephropathy: systematic reviews and network meta-analysis.

Background: Dietary soy protein (SP) is a potential intervention for protecting the kidneys and improving glucose and lipid metabolism. However, whether this effect is related to the percentage of SP intake remains unclear. Objective: This study aims to review and analyze the results of randomized clinical trials (RCTs) in patients with type 2 diabetic nephropathy (T2DN) who received diets with different percentages of SP. Methods: The databases: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), WanFang, Weipu (VIP), and ClinicalTrials.gov were searched until February 2023, for RCTs on T2DN and SP. Results: A total of six studies comprising 116 participants were included. The interventions were classified as 0% SP, 35% SP, and 100% SP. To improve serum creatinine (Scr), blood urea nitrogen (BUN), 24-h urine total protein (24hUTP), and glomerular filtration rate (GFR), a 35% SP diet was the most effective, compared to a 0% SP diet, which showed a mean difference of -154.00 (95% confidence interval: -266.69, -41.31) for 24hUTP. Although it had significant benefits for 24hUTP, great heterogeneity was observed. To improve the glycolipid metabolism-related markers such as cholesterol (CHO), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FPG), and weight, the 35% SP diet demonstrated superior efficacy compared to the 0% SP diet. Specifically, the mean difference for CHO was -0.55 (95% confidence interval: -1.08, -0.03), and for LDL-C, it was -17.71 (95% confidence interval: -39.67, -4.24). The other indicators were not statistically significant. Most studies had concerns regarding the risk of bias. Conclusion: The findings of this study demonstrate that both 35% and 100% SP diets are more effective than a diet with no SP in improving renal function and glucolipid metabolism in patients with T2DN. As a result, a diet incorporating 35% SP may be the optimal choice for individuals with T2DN. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=352638, identifier CRD42022352638.

Visualizing temporal dynamics and research trends of macrophage-related diabetes studies between 2000 and 2022: a bibliometric analysis.

Background: Macrophages are considered an essential source of inflammatory cytokines, which play a pivotal role in the development of diabetes and its sequent complications. Therefore, a better understanding of the intersection between the development of diabetes and macrophage is of massive importance. Objectives: In this study, we performed an informative bibliometric analysis to enlighten relevant research directions, provide valuable metrics for financing decisions, and help academics to gain a quick understanding of the current macrophage-related diabetes studies knowledge domain. Methods: The Web of Science Core Collection database was used for literature retrieval and dataset export. Bibliometrix R-package was performed to conduct raw data screening, calculating, and visualizing. Results: Between 2000 and 2022, the annual publication and citation trends steadily increased. Wu Yonggui was the scholar with the most published papers in this field. The institute with the highest number of published papers was the University of Michigan. The most robust academic collaboration was observed between China and the United States of America. Diabetologia was the journal that published the most relevant publications. The author's keywords with the highest occurrences were "inflammation", "diabetic nephropathy", and "obesity". In addition, "Macrophage polarization" was the current motor topic with potential research prospects. Conclusions: These comprehensive and visualized bibliometric results summarized the significant findings in macrophage-related diabetes studies over the past 20 years. It would enlighten subsequent studies from a macro viewpoint and is also expected to strengthen investment policies in future macrophage-related diabetes studies.

Is non-alcoholic fatty liver disease a sign of left ventricular diastolic dysfunction in patients with type 2 diabetes mellitus? A systematic review and meta-analysis.

Recent studies have associated non-alcoholic fatty liver disease (NAFLD) with impaired cardiac function. However, patients with type 2 diabetes mellitus (T2DM), a high-risk group for left ventricular diastolic dysfunction (LVDD), were not analyzed as an independent study population. A systematic review was conducted to identify all published clinical trials using the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases from inception to September 14, 2022. Observational studies that reported echocardiographic parameters in T2DM patients with NAFLD compared with those without NAFLD were included for further selection. The Agency for Healthcare Research and Quality checklist was used to appraise the study quality. Ten observational studies (all cross-sectional in design) comprising 1800 T2DM patients (1124 with NAFLD, 62.4%) were included. We found that T2DM patients with NAFLD had a significantly lower E/A ratio, higher peak A velocity, higher E/e' ratio, lower e' velocity, greater left atrial maximum volume index, and greater left ventricular mass index than non-NAFLD patients. These findings reinforced the importance of NAFLD being associated with an increased risk of LVDD in the T2DM population, and NAFLD may be a sign of LVDD in patients with T2DM.PROSPERO registration numberCRD42022355844.

Clinical potential and mechanistic insights of mulberry (Morus alba L.) leaves in managing type 2 diabetes mellitus: Focusing on gut microbiota, inflammation, and metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Natural herbs are gradually gaining recognition for their efficacy and safety in preventing diabetes and improving quality of life. Morus alba L. is a plant widely grown in Asia and is a traditional Chinese herb with a long history of use. Furthermore, several parts of Morus alba L. have been found to have significant health benefits. In particular, mulberry (Morus alba L.) leaves (ML) have been shown in human and animal studies to be promising hypoglycemic agents that can reduce or prevent glucolipid metabolism disorders caused by imbalances in the gut microbiota, inflammation, and oxidative stress and have demonstrated significant improvements in glucose metabolism-related markers, effectively lowering blood glucose, and reducing hyperglycemia-induced target organ damage. AIM OF THE STUDY: This review briefly summarizes the methods for obtaining ML's bioactive components, elaborates on the clinical potential of the relevant components in managing type 2 diabetes mellitus (T2DM), and focuses on the therapeutic mechanisms of gut microbiota, inflammation, oxidative stress, and metabolism, to provide more inspiration and directions for future research in the field of traditional natural plants for the management of T2DM and its complications. MATERIALS AND METHODS: Research on ML and its bioactive components was mainly performed using electronic databases, including PubMed, Google Scholar, and ScienceNet, to ensure the review's quality. In addition, master's and doctoral theses and ancient documents were consulted. RESULTS: In clinical studies, we found that ML could effectively reduce blood glucose, glycated hemoglobin, and homeostasis model assessment of insulin resistance in T2DM patients. Furthermore, many in vitro and in vivo experiments have found that ML is involved in various pathways that regulate glucolipid metabolism and resist diabetes while alleviating liver and kidney damage. CONCLUSIONS: As a potential natural anti-diabetic phytomedicine, an in-depth study of ML can provide new ideas and valuable references for applying traditional Chinese medicine to treat T2DM. While continuously exploring its clinical efficacy and therapeutic mechanism, the extraction method should be optimized to improve the efficacy of the bioactive components. in addition, further research on the dose-response relationship of drugs to determine the effective dose range is required.

Research status and trends of the diabetic cardiomyopathy in the past 10 years (2012-2021): A bibliometric analysis.

Background: Diabetic cardiomyopathy is one of the most life-threatening diabetic complications. However, the previous studies only discuss a particular aspect or characteristic of DCM, the current state and trends were explored by limited research. We aimed to perform a systemically bibliometric study of DCM research progress status in the past decade, visualize the internal conceptual structure and potential associations, and further explore the prospective study trends. Methods: Articles related to DCM published from January 2012 to December 2021 were collected in the Web of Science core collection (WoSCC) database on June 24, 2022. We exported all bibliographic records, including titles, abstracts, keywords, authorship, institutions, addresses, publishing sources, references, citation times, and year of publication. In addition, the journal Impact Factor and Hirsch index were obtained from the Journal Citation Report. We conducted the data screening, statistical analysis, and visualization via the Bibliometrix R package. VOS viewer software was employed to generate the collaboration network map among countries and institutions for better performance in visualization. Results: In total, 1,887 original research articles from 2012 to 2021 were identified. The number of annual publications rapidly increased from 107 to 278, and a drastic increase in citation times was observed in 2017-2019. As for global contributions, the United States was the most influential country with the highest international collaboration, while China was the most productive country. Professor Cai Lu was the most prolific author. Shandong University published the most articles. Cardiovascular Diabetology journal released the most DCM-related articles. "Metabolic Stress-induced Activation of FoxO1 Triggers Diabetic Cardiomyopathy in Mice" Battiprolu PK et al., J Clin Invest, 2012. was the most top-cited article regarding local citations. The top three keywords in terms of frequency were apoptosis, oxidative stress, and fibrosis. The analysis of future topic trends indicated that "Forkhead box protein O1," "Heart failure with preserved ejection fraction," "Dapagliflozin," "Thioredoxin," "Mitochondria dysfunction," "Glucose," "Pyroptosis," "Cardiac fibroblast" and "Long non-coding RNA" could be promising hotspots. Conclusion: This study provides meaningful insights into DCM, which is expected to assist cardiologists and endocrinologists in exploring frontiers and future research directions in the domain through a refined and concise summary.

Global research trends on the links between the gut microbiota and diabetes between 2001 and 2021: A bibliometrics and visualized study.

Background: Over the past 20 years, evidence has suggested that gut microbiota plays an important role in metabolic homeostasis. The relationship between gut microbiota and diabetes has become the focus of considerable scientific interest. With the sharp increase in publications in this area, it is imperative to analyze the relevant articles using bibliometrics methods. Methods: Publications on "the gut microbiota and diabetes" were retrieved and downloaded from the Web of Science Core Collection database. Microsoft Excel 2020, VOSviewer, CiteSpace 5.8.R3 and Co-Occurrence 9.94 software were used for data analysis and visualization. Country/academic institution, journal, author, subject category, keyword and reference were analyzed thoroughly. The cutting-edge directions in this field were also determined by analyzing keywords and key articles. Results: A total of 2,342 documents were included in the analysis; the number of articles in this field has increased yearly, particularly after 2010. China and the University of Copenhagen are the country and research institution associated with the largest number of publications. Nutrients have published 191 articles in this field, ranking first among highly productive journals in the number of publications. The researcher Cani PD affiliated with the University of Leuven, Belgium, published the greatest number of articles in this field between 2001 and 2021 and was also ranked as the first co-cited author and the largest contributor of highly cited papers in this field. Endocrinology & Metabolism was the most common subject category. Three of the most frequently found keywords, besides terms related to "microbiota" and "diabetes," were "obesity," "probiotics," and "inflammation." Akkermansia muciniphila, Faecalibacterium prausnitzii, trimethylamine n-oxide and branched-chain amino acids are intestinal bacteria or metabolites that have attracted more attention in recent years. Natural products represented by Chinese herbal medicine and some protein receptors or signaling pathways such as aryl hydrocarbon receptor, farnesoid X receptor and AMP-activated protein kinase were frontiers in this field. Conclusion: Over the past two decades, the rapid development of research on the gut microbiota has deepened the understanding of the physiology and pathology of diabetes, providing new insights into different approaches to treatment. In the future, further interdisciplinary innovation, clinical transformation, and application may receive more attention.

Herbal tea, a novel adjuvant therapy for treating type 2 diabetes mellitus: A review.

Type 2 diabetes mellitus (T2DM) is a metabolic, endocrine disease characterized by persistent hyperglycemia. Several studies have shown that herbal tea improves glucose metabolism disorders in patients with T2DM. This study summarizes the published randomized controlled trials (RCTs) on herbal tea as a adjuvant therapy for treating T2DM and found that herbal teas have potential add-on effects in lowering blood glucose levels. In addition, we discussed the polyphenol contents in common herbal teas and their possible adverse effects. To better guide the application of herbal teas, we further summarized the hypoglycemic mechanisms of common herbal teas, which mainly involve: 1) improving insulin resistance, 2) protecting islet ß-cells, 3) anti-inflammation and anti-oxidation, 4) inhibition of glucose absorption, and 5) suppression of gluconeogenesis. In conclusion, herbal tea, as a novel adjuvant therapy for treating T2DM, has the potential for further in-depth research and product development.

Evidence and Potential Mechanisms of Traditional Chinese Medicine for the Adjuvant Treatment of Coronary Heart Disease in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.

Traditional Chinese medicine (TCM) has long been used to treat diabetes mellitus and angina. It has also gained widespread clinical applications in China as a common adjuvant treatment. Although there is high-quality evidence that TCM is effective in regulating glucose and lipid metabolism, the cardiovascular protective effect of TCM in the treatment of diabetes mellitus has not been fully elucidated, especially in patients with both diabetes mellitus and coronary heart disease (CHD). We systematically assessed the efficacy and safety of TCM for the adjuvant treatment of patients with CHD and diabetes mellitus and examined the pharmacological effects and potential mechanisms of TCM medication/herbs on diabetes mellitus with CHD. We found that TCM could improve the control effect of conventional treatment on cardiac function, hemorheology, blood glucose, blood lipid, and inflammation, thus reducing the frequency of angina and the incidence of cardiovascular events and all-cause mortality. These findings indicate that TCM may be used as a complementary approach for patients with diabetes mellitus and CHD. Nevertheless, more rigorously designed randomized controlled trials and long-term evaluations are needed to support these findings.

Gut Microbiota: The Potential Key Target of TCM's Therapeutic Effect of Treating Different Diseases Using the Same Method-UC and T2DM as Examples.

Traditional Chinese herbal medicine often exerts the therapeutic effect of "treating different diseases with the same method" in clinical practice; in other words, it is a kind of herbal medicine that can often treat two or even multiple diseases; however, the biological mechanism underlying its multi-path and multi-target pharmacological effects remains unclear. Growing evidence has demonstrated that gut microbiota dysbiosis plays a vital role in the occurrence and development of several diseases, and that the root cause of herbal medicine plays a therapeutic role in different diseases, a phenomenon potentially related to the improvement of the gut microbiota. We used local intestinal diseases, such as ulcerative colitis, and systemic diseases, such as type 2 diabetes, as examples; comprehensively searched databases, such as PubMed, Web of Science, and China National Knowledge Infrastructure; and summarized the related studies. The results indicate that multiple individual Chinese herbal medicines, such as Rhizoma coptidis (Huang Lian), Curcuma longa L (Jiang Huang), and Radix Scutellariae (Huang Qin), and Chinese medicinal compounds, such as Gegen Qinlian Decoction, Banxia Xiexin Decoction, and Shenling Baizhu Powder, potentially treat these two diseases by enriching the diversity of the gut microbiota, increasing beneficial bacteria and butyrate-producing bacteria, reducing pathogenic bacteria, improving the intestinal mucosal barrier, and inhibiting intestinal and systemic inflammation. In conclusion, this study found that a variety of traditional Chinese herbal medicines can simultaneously treat ulcerative colitis and type 2 diabetes, and the gut microbiota may be a significant target for herbal medicine as it exerts its therapeutic effect of "treating different diseases with the same method".

Potential Role of Natural Plant Medicine Cyclocarya paliurus in the Treatment of Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a common chronic metabolic disease that has become increasingly prevalent worldwide. It poses a serious threat to human health and places a considerable burden on global social medical work. To meet the increasing demand for T2DM treatment, research on hypoglycemic drugs is rapidly developing. Cyclocarya paliurus (Batal.) Iljinskaja is a medicinal plant that grows in China. The leaves of C. paliurus contain polysaccharides, triterpenoids, and other chemical components, which have numerous health benefits. Therefore, the use of this plant has attracted extensive attention in the medical community. Over the past few decades, contemporary pharmacological studies on C. paliurus extracts have revealed that it has abundant biological activities. Multiple in vitro and in vivo experiments have shown that C. paliurus extracts are safe and can play a therapeutic role in T2DM through anti-inflammatory and antioxidation activities, and intestinal flora regulation. Its efficacy is closely related to many factors, such as extraction, separation, purification, and modification. Based on summarizing the existing extraction methods, this article further reviews the potential mechanism of C. paliurus extracts in T2DM treatment, and we aimed to provide a reference for future research on natural plant medicine for the prevention and treatment of T2DM and its related complications.

The Potential Roles of Artemisinin and Its Derivatives in the Treatment of Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic disease that has become a global public health problem. Studies on T2DM prevention and treatment mostly focus on discovering therapeutic drugs. Artemisinin and its derivatives were originally used as antimalarial treatments. In recent years, the roles of artemisinins in T2DM have attracted much attention. Artemisinin treatments not only attenuate insulin resistance and restore islet ß-cell function in T2DM but also have potential therapeutic effects on diabetic complications, including diabetic kidney disease, cognitive impairment, diabetic retinopathy, and diabetic cardiovascular disease. Many in vitro and in vivo experiments have confirmed the therapeutic utility of artemisinin and its derivatives on T2DM, but no article has systematically demonstrated the specific role artemisinin plays in the treatment of T2DM. This review summarizes the potential therapeutic effects and mechanism of artemisinin and its derivatives in T2DM and associated complications, providing a reference for subsequent related research.

Corrigendum: The Efficacy and Safety of Qiming Granule for Dry Eye Disease: A Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.3389/fphar.2020.00580.].

The Herbal Medicine Scutellaria-Coptis Alleviates Intestinal Mucosal Barrier Damage in Diabetic Rats by Inhibiting Inflammation and Modulating the Gut Microbiota.

Recent studies have confirmed that increased intestinal permeability and gut-origin lipopolysaccharide (LPS) translocation are important causes of metabolic inflammation in type 2 diabetes (T2D), but there are no recognized therapies for targeting this pathological state. Scutellaria baicalensis and Coptis chinensis are a classic herbal pair often used to treat diabetes and various intestinal diseases, and repair of intestinal barrier damage may be at the core of their therapeutic mechanism. This study investigated the effects of oral administration of Scutellaria-Coptis (SC) on the intestinal mucosal barrier in diabetic rats and explored the underlying mechanism from the perspective of anti-inflammatory and gut microbiota-modulatory effects. The main results showed that, in addition to regulating glycolipid metabolism disorders and inhibiting serum inflammatory factors, SC could also upregulate the expression levels of the tight junction proteins claudin-1, occludin, and zonula occludens (ZO-1), significantly improve intestinal epithelial damage, and inhibit excessive LPS translocation into the blood circulation. Furthermore, it was found that SC could reduce the levels of the inflammatory factors interleukin-1ß (IL-1ß), IL-6, and tumour necrosis factor-α (TNF-α) in intestinal tissue and that the anti-inflammatory effects involved the TLR-4/TRIF and TNFR-1/NF-κB signalling pathways. Moreover, SC had a strong inhibitory effect on some potential enteropathogenic bacteria and LPS-producing bacteria, such as Proteobacteria, Enterobacteriaceae, Enterobacter, Escherichia-Shigella, and Enterococcus, and could also promote the proliferation of butyrate-producing bacteria, such as Lachnospiraceae and Prevotellaceae. Taken together, the hypoglycaemic effects of SC were related to the protection of the intestinal mucosal barrier, and the mechanisms might be related to the inhibition of intestinal inflammation and the regulation of the gut microbiota.

Experimental study of expression profile and specific role of human microRNAs in regulating atrophic bone nonunion.

The expression profile and specific roles of microRNAs (miRNAs) in regulation of atrophic bone nonunion are not fully understood. Here, we present evidence that miRNAs are involved in regulation of several osteogenic genes and may contribute to the development of atrophic bone nonunion.The miRNA expression profile of repairing tissues in atrophic bone nonunion patients (group A) and in callus tissues from patients with healed fractures (group B) were quantitatively measured. microRNA microarrays were used to identify differentially expressed miRNAs, and the bioinformatics methods were used to predict the potential target genes. Quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and dual-luciferase reporter assay were performed in human bone marrow stromal cells (hBMSCs) to validate the microarray results.Nine miRNAs in group A were up-regulated 1.5 times compared to group B, while the other 9 miRNAs in group A were down-regulated 1.5 times. Several target regions of these miRNAs were identified in the osteogenic genes, as well as in the other genes in their families or related regulatory factors. Four miRNAs (hsa-miR-149, hsa-miR-221, hsa-miR-628-3p, and hsa-miR-654-5p) could play important roles in regulating bone nonunion development. hBMSCs transfected with these miRNAs significantly decreased mRNA levels of alkaline phosphatase, liver/bone/kidney (ALPL), platelet derived growth factor subunit A (PDGFA), and bone morphogenetic protein 2 (BMP2). Lower protein expression levels were observed using western blotting, confirming that ALPL, PDGFA, and BMP2 were directly targeted by hsa-miR-149, hsa-miR-221, and hsa-miR-654-5p, respectively.In summary, hsa-miR-149, hsa-miR-221, and hsa-miR-654-5p may play important biological roles by repressing osteogenic target genes ALPL, PDGFA, and BMP2, and, therefore, contributing to progression of atrophic bone nonunion.

The Efficacy and Safety of Qiming Granule for Dry Eye Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Dry eye disease (DED) is a common complication in clinical practice. Qiming granule, a traditional Chinese patent medicine, is widely used in treating DED in China. However, its effect is still largely unknown. OBJECTIVES: This research aims to evaluate the efficacy and safety of QG on DED. METHODS: Three English database and four Chinese databases without restriction on language and publication bias were searched. Qualified literature was selecting according to inclusion and exclusion criteria, extracted the data, and conducted a meta-analysis. RESULTS: A total of 11 articles were included in this meta-analysis. The methodological quality of included studies was low. The results showed that QG was effective for DED (RR:1.26, 95%CI:1.12 to 1.41, P=0.0001). The results combined with random effects model showed that QG could significantly prolong the tear film break up time (MD: 2.93, 95% CI: 2.22 to 3.65, P < 0.00001), increase the amount of tears in patients with DED (MD: 2.94, 95% CI: 1.83 to 4.04, P < 0.00001) and repair the corneal defects in patients (MD: -0.71, 95% CI: -1.25 to -0.17, P < 0.00001). CONCLUSIONS: This study found that despite of the apparently positive results of some outcomes, it is premature to confirm the efficacy of QG in treating DED. More high-quality studies are still needed in the future to further confirm the efficacy and safety.