Different microbial assemblage colonized on microplastics and clay particles in aerobic sludge treatment.

In this study, a combination of property analysis and high-throughput sequencing was used to investigate the microbial colonization ability and their community structures and functions in polypropylene microplastics (PPMPs), polystyrene microplastics (PSMPs) and montmorillonite (MMT), respectively as the representatives of artificial and natural substrates in aerobic sludge treatment. After 45 d of incubation, the surface properties of substrates were altered with the increased oxygen functional groups and surface roughness, indicating microbial settlement. Moreover, MPs had different microbial structures from that of MMT, and PSMPs exhibited higher microbial diversity and abundance than PPMPs and MMT. Also, these substrates changed the inherent ecological niche in sludge. Especially, the abundance of some pathogens (e.g., Pseudomonas, Klebsiella and Flavobacterium) was increased in MPs, and the disease risk of Kyoto Encyclopedia of Genes and Genomes metabolic pathway (e.g., Infectious diseases: Bacterial, Infectious diseases: Parasitic and Immune diseases) was higher. Also, the presence of MPs inhibited the decomposition of organic matter including soluble chemical oxygen demand and protein compared to natural substrates. The findings revealed the crucial vector role of MPs for microbes and the effect on aerobic sludge treatment, highlighting the necessity of MP removal in sludge.

3, 14, 19-Triacetyl Andrographolide alleviates the cognitive dysfunction of 3 × Tg-AD mice by inducing initiation and promoting degradation process of autophagy.

The present study aims to investigate the cognition-enhancing effect of 3, 14, 19-Triacetyl andrographolide (ADA) on learning and memory deficits in 3 × Tg-AD mice and to explore its underlying mechanism. Eight-month-old 3 × Tg-AD mice and C57BL/6J mice were randomly divided into three groups, namely wild-type group, 3 × Tg-AD group, and 3 × Tg-AD+ADA group (5 mg/kg, for 21 days, i.p.). We found that ADA significantly improved learning and cognition impairment, inhibited the loss of Nissl body, and reduced Aß load in the brains of 3 × Tg-AD mice. In addition, ADA enhanced the levels of PSD95 and SYP, which were closely associated with synaptic plasticity. Accumulated autophagosomes, LC3II, and P62 in hippocampus and cortex of 3 × Tg-AD mice were decreased by ADA treatment. Furthermore, ADA administration further down-regulated the expressions of p-AKT and p-mTOR, reduced the level of CTSB, and increased the co-localization of LC3 and LAMP1 in the brains of 3 × Tg-AD mice, implying that ADA-induced autophagy initiation and also promoted the degradation process. In Aß25-35 -induced HT22 cells, ADA displayed similar effects on autophagy flux as observed in 3 × Tg-AD mice. Our finding verified that ADA could improve synaptic plasticity and cognitive function, which is mainly attributed to the key roles of ADA in autophagy induction and degradation.

Effect of natural polyphenols in Chinese herbal medicine on obesity and diabetes: Interactions among gut microbiota, metabolism, and immunity.

With global prevalence, metabolic diseases, represented by obesity and type 2 diabetes mellitus (T2DM), have a huge burden on human health and medical expenses. It is estimated that obese population has doubled in recent 40 years, and population with diabetes will increase 1.5 times in next 25 years, which has inspired the pursuit of economical and effective prevention and treatment methods. Natural polyphenols are emerging as a class of natural bioactive compounds with potential beneficial effects on the alleviation of obesity and T2DM. In this review, we investigated the network interaction mechanism of "gut microbial disturbance, metabolic disorder, and immune imbalance" in both obesity and T2DM and systemically summarized their multiple targets in the treatment of obesity and T2DM, including enrichment of the beneficial gut microbiota (genera Bifidobacterium, Akkermansia, and Lactobacillus) and upregulation of the levels of gut microbiota-derived metabolites [short-chain fatty acids (SCFAs)] and bile acids (BAs). Moreover, we explored their effect on host glucolipid metabolism, the AMPK pathway, and immune modulation via the inhibition of pro-inflammatory immune cells (M1-like Mϕs, Th1, and Th17 cells); proliferation, recruitment, differentiation, and function; and related cytokines (TNF-α, IL-1ß, IL-6, IL-17, and MCP-1). We hope to provide evidence to promote the clinical application of natural polyphenols in the management of obesity and T2DM.

Network Pharmacology-Based Prediction of Mechanism of Shenzhuo Formula for Application to DKD.

BACKGROUND: Shenzhuo formula (SZF) is a traditional Chinese medicine (TCM) prescription which has significant therapeutic effects on diabetic kidney disease (DKD). However, its mechanism remains unknown. Therefore, this study aimed to explore the underlying anti-DKD mechanism of SZF. METHODS: The active ingredients and targets of SZF were obtained by searching TCMSP, TCMID, SwissTargetPrediction, HIT, and literature. The DKD target was identified from TTD, DrugBank, and DisGeNet. The potential targets were obtained and PPI network were built after mapping SZF targets and DKD targets. The key targets were screened out by network topology and the "SZF-key targets-DKD" network was constructed by Cytoscape. GO analysis and KEGG pathway enrichment analysis were performed by using DAVID, and the results were visualized by Omicshare Tools. RESULTS: We obtained 182 potential targets and 30 key targets. Furthermore, a "SZF-key targets-DKD" network topological analysis showed that active ingredients like M51, M21, M5, M71, and M28 and targets like EGFR, MMP9, MAPK8, PIK3CA, and STAT3 might play important roles in the process of SZF treating in DKD. GO analysis results showed that targets were mainly involved in positive regulation of transcription from RNA polymerase II promoter, inflammatory response, lipopolysaccharide-mediated signaling pathway, and other biological processes. KEGG showed that DKD-related pathways like TNF signaling pathway and PI3K-Akt signaling pathway were at the top of the list. CONCLUSION: This research reveals the potential pharmacological targets of SZF in the treatment of DKD through network pharmacology and lays a foundation for further studies.

Therapeutic mechanisms of traditional Chinese medicine to improve metabolic diseases via the gut microbiota.

Metabolic diseases such as obesity, type 2 diabetes mellitus, and hyperlipidemia are associated with the dysfunction of gut microbiota. Traditional Chinese medicines (TCMs) have shown considerable effects in the treatment of metabolic disorders by regulating the gut microbiota. However, the underlying mechanisms are unclear. Studies have shown that TCMs significantly affect glucose and lipid metabolism by modulating the gut microbiota, particularly mucin-degrading bacteria, bacteria with anti-inflammatory properties, lipopolysaccharide- and short-chain fatty acid (SCFA)-producing bacteria, and bacteria with bile-salt hydrolase activity. In this review, we explored potential mechanisms by which TCM improved metabolic disorders via regulating gut microbiota composition and functional structure. In particular, we focused on the protection of the intestinal barrier function, modulation of metabolic endotoxemia and inflammatory responses, regulation of the effects of SCFAs, modulation of the gut-brain axis, and regulation of bile acid metabolism and tryptophan metabolism as therapeutic mechanisms of TCMs in metabolic diseases.

Incipient Diabetes Treated with Long-Term Classical Prescription.

BACKGROUND: Diabetes mellitus (DM) belongs to the progressive and irreversible disease. With the development of the disease, the function of beta cells declines significantly. Current treatments cannot reverse the course of the disease. The role of traditional Chinese medicine (TCM) in the DM treatment has been recognized widely, while there are few long-term observation reports. In this study, we introduced a case of DM treated by classical prescription alone for 10 years, which would provide the reference for clinical practice. CASE PRESENTATION: A 64-year-old male complained of a 2-month history of dry mouth, frequent urination, and blurred vision and found increased blood glucose for 3 days. The patient's glycated hemoglobin was 14.2%, fasting plasma glucose fluctuated at 12-15 mmol/L, and urinary albumin excretion rate (UAER) was 32.9 µg/min. The male was treated with 10 years of continuous classical prescription alone. After 3 months of TCM treatment, the patient's blood glucose level decreased significantly and blurred vision symptoms improved. With continued TCM treatment, his UAER normalized. Subsequently, he continued outpatient consultation, and his TCM prescription was adjusted according to clinical symptoms. After 10 years of continuous TCM treatment, his blood glucose remained stable, urinary microalbumin quantitation showed no abnormalities, and blurred vision disappeared. CONCLUSIONS: This case provides specific treatment plans and effective references for long-term control of blood glucose, prevention and treatment of diabetes complications, delay of disease progression, and protection of impaired islet function in the treatment of diabetes with TCM. TCM may become a meaningful alternative DM treatment in the future.

The interaction between the gut Microbiota and herbal medicines.

As technologies used to study the gut microbiota have improved, the relationship between the gut microbiota and health has become increasingly obvious. Herbal medicines have been used for thousands of years, and are known to be "simple, convenient, cheap, and effective". However, due to many factors, such as their complex composition, unclear active compounds, and poor knowledge of their underlying mechanisms, the clinical applications of herbal medicines are not widely recognized. Recently, there have been an increasing number of studies which have investigated the interaction between the gut microbiota and herbal medicines. We have found that interactions between the gut microbiota and herbal medicines occur primarily through two pathways. One pathway is that the gut microbiota "digests" the herbal medicines into absorbable active small molecules, which enter the body and induce physiological changes. The other is that herbal medicines regulate the composition of the gut microbiota and its secretions, thereby changed gut microbiota and its secretions inducing physiological changes. In summary, the interactions between the gut microbiota and herbal medicines can be attributed to absorbable active small molecules and changed gut microbiota and its secretions. Our findings will aid the exploration of the mechanisms and pathways underlying the function of herbal medicines in the future. This review also summarizes the direction of future research and the main problems faced by the current researchers.

Does Adjuvant Treatment with Chinese Herbal Medicine to Antidiabetic Agents Have Additional Benefits in Patients with Type 2 Diabetes? A System Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: In the present meta-analysis, we aimed to determine the effects of adjuvant treatment with Chinese herbal medicine (CHM) on antidiabetic agents having additional benefits in patients with type 2 diabetes. METHODS: Randomized controlled trials were identified by searching the Cochrane Library, PUBMED, EMBASE, MEDLINE, the China National Knowledge Internet, Web of Science, Global Health, International Pharmaceutical Abstracts and the China biology medicine, Wanfang, and VIP databases. The intervention group received CHM as add-on treatment to antidiabetic agents therapy, and the control group received placebos in addition to antidiabetic agents or antidiabetic agents alone. We assessed pooled data, including weighted mean differences and 95% confidence intervals (CIs) using a random-effects model. RESULTS: A total of 125 randomized controlled trials were included. 10 articles were included based on literature screening. All trials contrasted Chinese herbal medicines or Chinese herbal medicines + antidiabetic agents with placebo or antidiabetic agents + placebo and included a total of 2004 individuals with T2DM. All selected trials displayed evidence of high methodological quality and possessed a low risk of bias. Meta-analysis of the trials demonstrated that Chinese herbal medicines resulted in a more favorable blood glucose profile in contrast to placebo (P<0.05). The total efficacy rate differed significantly between the two groups (P<0.001). All ten included studies reported the occurrence of tolerable adverse effects. CONCLUSIONS: The results showed that in the intervention group, greater reductions were achieved for glucose control and body weight. The combined use of drugs improves the curative effect and has fewer adverse events and has additional benefits in patients with type 2 diabetes. This trial is registered with PROSPERO (CRD42018093867).

Effects of doxazosin mesylate versus nifedipine on blood pressure variability in hypertensive patients: a randomized crossover study (SIMILAR).

OBJECTIVE: Blood pressure variability (BPV) is a powerful predictor of end-organ damage, cardiovascular events and mortality independently of the BP level. Calcium channel blockers may offer an advantage over other first-line antihypertensive drugs by preventing increased BPV. But the effect of alpha-receptor blockers on BPV in hypertensive patients is still unclear. METHODS: In this crossover trial, 36 hypertensive patients were randomly assigned to two groups, receiving doxazosin mesylate gastrointestinal therapeutic system (GITS) (4 mg/day) or nifedipine GITS (30 mg/day) for 12 weeks, followed by a 2-week washout period then a 12-week crossover phase. At baseline and after 12-week treatment, 24-hour ambulatory BP monitoring was performed. BPV was evaluated through standard deviation (SD), coefficient of variation (CV), and average real variability (ARV) of systolic BP (SBP) and diastolic BP (DBP) during daytime, nighttime and over 24 hours. RESULTS: After 12-week treatment, both doxazosin and nifedipine significantly decreased SBP and DBP (P < 0.05), whereas no between-group differences were shown (P>0.05). Systolic BPV (24-hour SD, CV, and ARV; daytime SD; nighttime SD and CV) and diastolic BPV (24-hour SD and ARV) were significantly lowered by nifedipine (P < 0.05); doxazosin resulted in significant reductions of systolic BPV (24-hour SD, CV and ARV; daytime SD; nighttime SD) and diastolic BPV (nighttime SD and CV) (P < 0.05). Doxazosin was revealed to be as effective as nifedipine for reducing BPV (P > 0.05) except for 24-hour SBP ARV. CONCLUSIONS: Doxazosin mesylate GITS had similar therapeutic effects on BP, BP SD, and BP CV lowering as nifedipine GITS in patients with mild-to-moderate essential hypertension.

Evidence and potential mechanisms of traditional Chinese medicine for the treatment of type 2 diabetes: A systematic review and meta-analysis.

Traditional Chinese medicine (TCM) has recorded knowledge of diabetes for over 2000 years. Because a considerable number of TCM studies exhibit design defects, such as limited intervention duration, small sample sizes and inconsistent efficacy evaluations, the role of TCM in the treatment of diabetes cannot be fully elucidated. In this review, we evaluate randomized controlled trials of prediabetes, diabetes and diabetic complications published in the past decade. We found that TCM could significantly improve glucose control and clinical indices in patients with diabetes and effectively delay the progression of diabetes. We also summarize potential pharmacological mechanisms underlying the efficacy of TCM medication/herbs and their active ingredients for treating diabetes. More rigorously designed experiments and long-term evaluation of TCM for diabetes will allow for more effective diabetes management.