Probiotic Supplement for the Prevention of Gestational Diabetes: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Probiotic supplements may have some potential in preventing gestational diabetes, and this meta-analysis aims to explore the efficacy of probiotic supplements to prevent gestational diabetes. METHODS: PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched, and we included randomized controlled trials (RCTs) assessing the effect of probiotic supplements on the incidence of gestational diabetes mellitus. Meta-analysis was performed using the fixed-effect or random-effect model as appropriate. RESULTS: Six RCTs were finally included in the meta-analysis. Overall, compared with control intervention in pregnant women, probiotic supplementation intervention showed no obvious impact on the incidence of gestational diabetes (OR=0.68; 95% CI=0.39 to 1.20; P=0.18), fasting plasma glucose (SMD=-0.05; 95% CI=-0.29 to 0.19; P=0.69), 2 h-OGTT (SMD=-0.07; 95% CI=-0.27 to 0.13; P=0.47), gestational age (SMD=0.04; 95% CI=-0.14 to 0.21; P=0.69) or preeclampsia (OR=1.22; 95% CI=0.83 to 1.78; P=0.31). CONCLUSIONS: Probiotic supplementation was confirmed to have no benefits for the prevention of gestational diabetes.

Systematic review and meta-analysis of Coptis chinensis Franch.-containing traditional Chinese medicine as an adjunct therapy to metformin in the treatment of type 2 diabetes mellitus.

Background: In China, Coptis chinensis Franch. (Chinese name: Huanglian) prescriptions (HLPs) are prominent hypoglycemic agents used in glycemic control. However, the curative effect of HLPs as adjunctive therapies for type 2 diabetes mellitus (T2DM) has not been evaluated. Based on a systematic review and a meta-analysis, this study was conducted to assess the effects of HLPs combined with metformin as a reinforcing agent for T2DM. Materials and methods: A total of 33 randomized controlled trials (RCTs) reporting on 2,846 cases concerning the use of HLPs in the treatment of T2DM were identified from the China National Knowledge Infrastructure (CNKI), Weipu (VIP), Wanfang, PubMed, Cochrane Library, and EMBASE databases. Primary outcomes included fasting blood glucose (FBG), 2-h postprandial blood glucose (2hPG), glycosylated hemoglobin, type A1c (HbA1c), fasting serum insulin (FINS), and homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes included total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and gastrointestinal dysfunction (GD). Continuous data were expressed as mean differences (MDs) with 95% confidence intervals (CIs). The methodological quality of the included RCTs was assessed by Cochrane evidence-based medicine systematic evaluation. Statistical analysis was performed using the Review Manager and Stata software. The required information size and treatment benefits were evaluated by trial sequential analysis (TSA). The quality of evidence was rated using the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Results: The results revealed that HLPs are beneficial to improve the following: FBG (MD = -1.16%, 95% CI: -1.24 to -1.07), 2hPG (MD = -1.64%, 95% CI: -1.84 to -1.43), HbA1c (MD = -0.78%, 95% CI:-0.96 to -0.60), FINS (MD = -1.94%, 95% CI: -2.68 to -1.20), HOMA-IR (MD = -0.77%, 95% CI: -1.28 to -0.27), TC (MD = -0.70%, 95% CI: -1.00 to -0.39), TG (MD = -0.57%, 95% CI: -0.74 to -0.40), LDL-c (MD = -0.70%, 95% CI: -0.97 to -0.43), and HDL-c (MD = -0.21%, 95% CI: -0.32 to -0.10) for patients with T2DM. The funnel plot, Egger's test, and trim-and-fill method indicated a moderate publication bias in the results. The TSA showed that the required sample size of HLPs in improving FBG, 2hPG, HbA1c, FINS, HOMA-IR, TC, TG, LDL-c, and HDL-c could sufficiently draw reliable conclusions. GRADE assessment revealed that the quality of the evidence for the effectiveness of HLPs in improving FBG was moderate, but the quality of evidence for 2hPG, HbA1c, FINS, HOMA-IR, TC, TG, LDL-c, and HDL-c was low, and for GD was very low. Conclusion: The systematic review and meta-analysis suggested that HLPs were beneficial for achieving glycemic control. However, HLPs recommended for T2DM patients have yet to be confirmed because of the poor methodological quality of some trials. Therefore, more RCTs with multicenter and double-blind designs are needed to assess the efficacy of HLPs for patients with T2DM.

Corrigendum: Systematic review and meta-analysis of Coptis Chinensis Franch. -containing traditional Chinese medicine as an adjunct therapy to metformin in the treatment of type 2 diabetes mellitus.

[This corrects the article DOI: 10.3389/fphar.2022.956313.].

TMT-based proteomics analysis reveals the efficacy of jiangzhuo formula in improving the lipid profiles of dyslipidemia rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiangzhuo Formula (JZF) is a traditional Chinese herbal prescription that is clinically applied to treat dyslipidemia. However, the mechanism underlying its efficacy remains unexplored. AIM OF THE STUDY: This study aims to elucidate the underlying mechanisms, explore potential pathways, and identify the key proteins of JZF for the treatment of dyslipidemia. METHODS: In this work, Q-Orbitrap high-resolution liquid chromatography mass spectrometry was used to identify the natural ingredients in JZF, rats with dyslipidemia were established via a high-fat diet for four weeks, then the dyslipidemia rats were treated with high-dose JZF (9 g/d) and low-dose JZF (4.5 g/d) for four weeks. After treatment, serum lipid detection and Oil-red-O staining were conducted to assess the efficacy of JZF in ameliorating dyslipidemia. Tandem mass tag (TMT) -based quantitative proteomics technology was then used to evaluate the roles and importance of proteins from the extracted hepatic tissue. The differentially expressed proteins were assessed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, Gene Ontology (GO), and protein-protein interaction (PPI) networks. Western blot and PCR analysis were used to validate the potential targets regulated by JZF. RESULTS: JZF could significantly improve the blood lipid profiles of serum and fat deposits of the liver. A total of 123 differentially expressed proteins were detected after JZF intervention, comprising 65 up-regulated proteins and 58 down-regulated proteins. The KEGG pathway analysis revealed that cholesterol metabolism, the PPAR signaling pathway, and bile secretion were the principal pathways involved in the disordered lipid metabolism, while GO analysis suggested that proteins that are located in the cell, regulate cellular processes, and show binding activity contribute to reductions in lipids. The combination of proteomics, Western blot, and PCR suggested that Apolipoprotein B (APOB), Apolipoprotein E (APOE), cholesterol 7 alpha-hydroxylase A1 (CYP7A1), and Hydroxymethylglutaryl-CoA synthase 1 (HMGCS1) might play critical roles in JZF's lipid-lowering network. CONCLUSION: JZF can effectively improve lipid profiles via multiple pathways involved in cholesterol metabolism, the PPAR signaling pathway, and bile secretion. Generally, the proteomics techniques used in this research show that JZF could be a promising drug for the treatment of dyslipidemia.

Identifying the Mechanisms and Molecular Targets of Yizhiqingxin Formula on Alzheimer's Disease: Coupling Network Pharmacology with GEO Database.

BACKGROUND: Yizhiqingxin formula (YZQX) is a promising formula for the treatment of Alzheimer's disease (AD) with significant clinical effects. Here, we coupled a network pharmacology approach with the Gene Expression Omnibus (GEO) database to illustrate comprehensive mechanisms and screen for molecular targets of YZQX for AD treatment. METHODS: First, active ingredients of YZQX were screened for the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database with the absorption, distribution, metabolism, and excretion (ADME) parameters. Subsequently, putative targets of active ingredients were predicted using the DrugBank database. AD-related targets were retrieved by analyzing published microarray data (accession number GSE5281). Protein-protein interaction (PPI) networks of YZQX putative targets and AD-related targets were constructed visually and merged to identify candidate targets for YZQX against AD using Cytoscape 3.7.2 software. We performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to further clarify the biological functions of the candidate targets. The gene-pathway network was established to filter for key target genes. RESULTS: Forty-three active ingredients were identified, and 193 putative target genes were predicted. Seven hundred and ten targets related to AD were screened with |log2 FC| > 1 and P < 0.05. Based on the PPI network, 110 target genes of YZQX against AD were identified. Moreover, 32 related pathways including the PI3K-Akt signaling pathway, MAPK signaling pathway, ubiquitin-mediated proteolysis, apoptosis and the NF-kappa B signaling pathway were significantly enriched. In the gene-pathway network, MAPK1, AKT1, TP53, MDM2, EGFR, RELA, SRC, GRB2, CUL1, and MYC targets are putative core genes for YZQX in AD treatment. CONCLUSION: YZQX against AD may exert its neuroprotective effect via the PI3K-Akt signaling pathway, MAPK signaling pathway, and ubiquitin-mediated proteolysis. YZQX may be a promising drug that can be used in the treatment of AD.

Network pharmacology and metabolomics study on the intervention of traditional Chinese medicine Huanglian Decoction in rats with type 2 diabetes mellitus.

ETHNOPHARMACOLOGICAL RELEVANCE: Type 2 diabetes mellitus (T2DM) is currently one of the most prominent and global chronic conditions. Huanglian Decoction (HLD) is a traditional Chinese medicine (TCM) preparation that has been used to treat T2DM for thousands of years in China. However, its mechanism of action at the metabolic level is still unclear. The purpose of this work is to study the mechanism of HLD in treating T2DM based on metabolomics and network pharmacology. MATERIALS AND METHODS: In this study, metabolomics combined with network pharmacology was used to elucidate the therapeutic mechanism of HLD in T2DM. Serum samples were collected from rats with T2DM, induced by a high-sugar and high-fat diet combined with streptozotocin (STZ), to measure the levels of biochemical markers. Urinary metabolomics-based analysis using high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS) was conducted to evaluate the differential metabolites from multiple metabolic pathways. RESULTS: After treatment with HLD for 4 weeks, biochemical indicators, including fasting blood glucose (FBG), blood lipid, fasting insulin (FINS), insulin sensitivity index (ISI), and homeostasis model assessment of insulin resistance (HOMA-IR), were significantly improved. Metabolomics results revealed that HLD regulated the biomarkers, such as cytosine, L-carnitine, betaine, phenylalanine, glucose, citrate, phenylpyruvate, and hippuric acid in glyoxylate and dicarboxylate metabolism, phenylalanine metabolism, and tricarboxylic acid (TCA) cycle. The combination of network pharmacology, metabolomics, western blot, and PCR showed that HLD can treat T2DM by enhancing the gene and protein expression levels of glucose transporter 4 (GLUT4), insulin receptor (INSR), and mitogen-activated protein kinase 1 (MAPK1) to interfere with glyoxylate and dicarboxylate metabolism. CONCLUSIONS: The study based on metabolomics and network pharmacology indicated that HLD can improve T2DM through multiple targets and pathways, and it may be a useful alternative therapy for the treatment of T2DM.

Urinary Metabolomics Study of the Intervention Effect of Hypoglycemic Decoction on Type 2 Diabetes Mellitus Rats Model.

The hypoglycemic decoction (HD) is a traditional Chinese medicine (TCM) preparation for the treatment of diabetes mellitus (DM), with a remarkable therapeutic effect. However, its mechanism of action is still unclear at the metabolic level. In this study, the biochemical markers from type 2 DM (T2DM) rats, induced by a high-sugar and high-fat diet combined with streptozotocin (STZ), were detected. The metabolomics-based analysis using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was conducted to evaluate urine samples from control, model, metformin, and HD groups. After oral administration of HD for 28 days, the general state, weight, fasting blood glucose (FBG), blood lipid level, oral glucose tolerance test (OGTT), fasting insulin (FINS), insulin sensitivity index (ISI), and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly improved (P < 0.01). The western blotting showed that HD can enhance the protein expression of glucose transporter 4 (GLUT4) and adenosine monophosphate-activated protein kinase (AMPK). The metabolomics results revealed that after treatment with HD, the levels of L-carnitine, 1-methyladenosine, 1-methylhistamine, and 3-indoleacrylic acid were upregulated and the levels of riboflavin, phenylalanine, atrolactic acid, 2-oxoglutarate, citrate, isocitrate, cortisol, and glucose were downregulated. The main mechanism may be closely related to the regulation of the tricarboxylic acid (TCA) cycle, phenylalanine metabolism, glyoxylate metabolism, and dicarboxylate metabolism. Additionally, it was also found that HD can regulate the protein expression of GLUT4 and AMPK to interfere with TCA cycle and carbohydrate metabolism to treat T2DM.

Ginsenoside Rg3 (Shenyi Capsule) Combined with Chemotherapy for Digestive System Cancer in China: A Meta-Analysis and Systematic Review.

OBJECTIVE: In China, ginsenoside Rg3 is often used in combination with chemotherapy to treat digestive system cancer. We here performed a meta-analysis and systematic review to provide a much needed high-quality evaluation of the efficacy and safety of ginsenoside Rg3 combined with chemotherapy in these cancers. MATERIALS AND METHODS: The PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu (VIP) databases were searched. All randomized controlled trials (RCTs) concerning ginsenoside Rg3 combined with chemotherapy for digestive system cancer were selected. Dichotomous data were expressed as odds ratios (ORs) with 95% confidence intervals (CI). The methodological quality of the included studies was evaluated according to the Cochrane evidence-based medicine system, and the statistical analyses were performed with Review Manager 5.3 and STATA 12.0 software. In addition, the Grades of Recommendation Assessment, Development and Evaluation (GRADE) approach was used to rate the quality of the evidence. Trial sequential analysis (TSA) was used to evaluate information size and treatment benefits. RESULTS: A total of 18 trials comprising 1531 patients were included in this study. The results revealed that the trials were of sufficient standard to draw reliable conclusions that ginsenoside Rg3 combined with chemotherapy could improve the objective response rate (ORR; OR 2.17, 95% CI 1.72-2.73), disease control rate (DCR; OR 2.83, 95% CI 2.02-3.96), 1-year survival rate (SR; OR = 2.33, 95% CI = 1.24-4.37), Karnofsky Performance Scale (KPS; OR 2.67, 95% CI 1.76-4.03), gastrointestinal dysfunction (OR 0.44, 95% CI 0.31-0.61), and the decline of leucocyte count (OR 0.28, 95% CI 0.21-0.38). CONCLUSION: Ginsenoside Rg3 combined with chemotherapy can improve the clinical efficacy and alleviate treatment-induced side effects for digestive system cancer.

An NMR-Based Metabolomic Approach to Unravel the Preventive Effect of Water-Soluble Extract from Dendrobium officinale Kimura & Migo on Streptozotocin-Induced Diabetes in Mice.

Dendrobium officinale Kimura & Migo (D. officinale) is a precious herbal medicine. In this study, we investigated metabolic mechanism underlying the effect of D. officinale water extract (DOWE) on diabetes prevention in mice after streptozotocin (STZ) exposure using NMR-based metabolomics. Interestingly, we found a decrease in blood glucose and an increase in liver glycogen in mice pretreated with DOWE after STZ exposure. The DOWE pretreatment significantly increased citrate and glutamine in the serum as well as creatine, alanine, leucine, isoleucine, valine, glutamine, glutathione and taurine in the liver of STZ-treated mice. Furthermore, serum glucose was significantly negatively correlated with citrate, pyruvate, alanine, isoleucine, histidine and glutamine in the serum as well as alanine and taurine in the liver. These findings suggest that the effect of DOWE on diabetes prevention may be linked to increases in liver glycogen and taurine as well as the up-regulation of energy and amino acid metabolism.

Secondary breast carcinoma after completely remitted chronic myeloid leukemia following targeted tyrosine kinase inhibitor therapy.

We describe a rare case of secondary breast carcinoma after chronic myeloid leukemia (CML) in a 56-year-old woman. The patient was treated with hydroxyurea and imatinib for CML and achieved complete remission (she has since been taking imatinib as the maintenance therapy). Four years later, the patient noticed a firm and painless lump in the left breast, which was diagnosed as ductal carcinoma in situ based on a percutaneous biopsy of the mass. Simple resection and sentinel lymph node biopsy of the left breast were then performed. Pathological studies revealed a medium-grade intraductal carcinoma, with local infiltration associated with invasive micropapillary carcinoma. She received adjuvant endocrine therapy with imatinib after surgery. Breast cancer secondary to CML (treated with imatinib and completely remitted) is extremely rare. This report provides evidence to assist in the diagnosis and treatment for this rare manifestation.

Liraglutide protects pancreatic beta cells during an early intervention in Gato-Kakizaki rats.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) analogues have emerged as insulin secretagogues and are widely used in type 2 diabetic patients. GLP-1 analogues also demonstrate a promotion of beta cell proliferation and reduction of apoptosis in rodents. In the present study, we investigated the protection of pancreatic beta cells by early use (at the age of 2 weeks) of GLP-1 analogue, liraglutide in Gato-Kakizaki (GK) rats and explored the underlying mechanisms. METHODS: The effects of liraglutide on glucose tolerance were evaluated by intraperitoneal glucose tolerance test (IPGTT) and insulin release tests (IRT). Ki67 and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) immunostaining, Western blots and real-time polymerase chain reaction were applied to evaluate cell proliferation, apoptosis and related gene expressions. RESULTS: Our results demonstrated that early use of liraglutide improved glucose tolerance during liraglutide treatment in GK rats. Liraglutide increased pancreatic insulin contents and markedly reduced beta cell apoptosis. Liraglutide also downregulated pro-apoptotic gene expressions and reduced intra-islet macrophage infiltration. CONCLUSIONS: This experiment reported for the first time that early use of liraglutide could protect beta cell failure in pre-diabetic GK rats through reduction of beta cell apoptosis and ameliorating islet inflammation.