Ginkgo biloba extract ameliorates hyperglycaemia-induced enteric glial cell injury via regulation of the TLR2-related pathway.

BACKGROUND: Diabetic gastrointestinal dysfunction (DGD) is a common complication in diabetic patients, and enteric glial cells (EGCs) found in the gastrointestinal tract have been shown to play an essential role in gastrointestinal dysfunction. Thus, targeting EGCs may be helpful for the control of DGD. This study aimed to evaluate the protective effect of Ginkgo biloba extract (GBE) from G. biloba dropping pills against hyperglycaemic stress-induced EGCs injury and its underlying mechanism. METHODS: In vitro, the protective effect of GBE on CRL-2690 cells was evaluated by MTT assay and TUNEL assay. The expression of related markers was evaluated by RNA sequencing and validated by using western blotting. In vivo, STZ-induced C57BL/6J WT mice were used as models to evaluate the effects of GBE on blood glucose, body weight, and EGCs' activity and relevant signalling pathways were validated by immunofluorescence. RESULTS: The results showed that GBE (25 µg/ml) treatment significantly attenuated hyperglycaemic stress-induced cytotoxicity and cell apoptosis in CRL-2690 cells, which was verified in an STZ-induced (100 mg/kg, 3 days) diabetic mouse model with continuous GBE administration (25/100 mg/kg/day, 6/12 weeks). Further mechanistic study based on transcriptomic data revealed that GBE exerted its beneficial effect by regulating immune-related pathways, and TLR2/BTK/NF-κB/IL-1α/IL-10 comprised the main targets of this drug. CONCLUSIONS: This study demonstrates the protective effect of GBE against hyperglycaemic stress-induced EGCs injury using both in vitro and in vivo models and further reveals that the effect was achieved by targeting TLR2 and its downstream molecules BTK/NF-κB/IL-1α/IL-10. This study may be helpful for expanding the clinical application of GBE in treating DGD.

Effect of Electroacupuncture with Different Current Intensities on the Serum Metabolomics of Functional Constipation.

Objective: The aim of the study is to investigate the serum metabolomics of electroacupuncture (EA) with different current intensities in the treatment of functional constipation (FC). Methods: The total number of FC patients was 19, (7, 6, 6, in the low current intensity group (LCI), high current intensity group (HCI), and mosapride citrate tablet control group (MC), respectively). Patients in the EA groups received 16 sessions of acupuncture treatments. Patients in the MC group were orally administered 5 mg mosapride citrate tablets 3 times daily, and serum samples were collected from the patients before and after treatment. Orthogonal partial least square-discriminant analysis (OPLS-DA) was used to assess the metabolic data. The significant differences before and after FC treatment are shown in the OPLS-DA score plot. Variable importance plots (VIPs) and T tests were used to identify significant metabolites. Results: Among the three groups, the number of metabolites with VIP > 1 was 11, 7, and 21 (in LCI, HCI and MC groups, respectively). Compared with those before treatment, the serum metabolites of patients were characterized by increased levels of L-ornithine (p < 0.05) and glyceric acid in the LCI group (p < 0.05), increased levels of vanillic acid in the MC group (p < 0.05), and decreased levels of arabinonic acid in the MC group (p < 0.05). Conclusions: The effects of EA treatment on the serum metabolomics of FC may involve fatty acid and amino acid metabolism.

Oral Chinese patent medicines for acute myocardial infarction after percutaneous coronary intervention: A protocol for systematic review and network meta-analysis.

BACKGROUND: Acute myocardial infarction (AMI) is a serious and fatal heart disease with one of the highest mortality rates in the world. In some countries, percutaneous coronary intervention (PCI) is the preferred reperfusion strategy after AMI, but it cannot achieve safe and effective treatment of AMI after PCI remains a challenging clinical problem. The potential of oral Chinese patent medicines to treat AMI after PCI has been demonstrated, but which type of oral Chinese patent medicines may be preferred remains controversial. The aim of this network meta-analysis was to investigate the efficacy and safety of multiple oral Chinese patent medicines in the treatment of AMI after PCI. METHODS: We will conduct a literature search from China National Knowledge Infrastructure, formerly Chinese Biomedical Database (SinoMed), Wanfang Data, Chongqing VIP, PubMed, Embase, Web of Science and Cochrane Library (The Cochrane Database of Systematic Reviews) from their inception until to November 1, 2022, with language restricted to Chinese and English. Then, the study selection process will follow the Preferred Reporting Items for Meta-Analyses guideline, and the quality assessment will be conducted with Cochrane Collaboration's tool. Pairwise and network meta-analysis will be conducted using the WinBUGS V.1.4.3.37 and STATA V.13. Additionally, sensitivity analysis, subgroup analysis, quality assessment, Small-study effects and publication bias will be performed. ETHICS AND DISSEMINATION: This work is based on published research and therefore does not require ethical approval. This review will be published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42020188065.

Icariin Ameliorates Amyloid Pathologies by Maintaining Homeostasis of Autophagic Systems in Aß1-42-Injected Rats.

Macroautophagy, a sole pathway for dysfunctional organelles or aggregated proteins turnover, has been implicated in the early development of Alzheimer's disease (AD). Previous studies have found that reversal of autophagy dysfunction in APP transgenic mice ameliorates amyloid pathologies. Icariin (ICA), the main component from traditional Chinese herb Epimedium brevicornu Maxim., can reduce accumulations of amyloid-ß (Aß) peptide in vivo and in vitro, but the mechanism remains unclear. Here, we explored the effects of ICA on autophagy-lysosomal pathway in intracerebroventricular (icv) injection of human Aß1-42 peptide rats. We demonstrated that feeding the rats with ICA (30 mg/kg, 60 mg/kg and 90 mg/kg rat, per os) for 4 weeks rescued the Aß1-42-induced spatial memory impairments, reduced endogenous rat Aß42 tested by ELISA and decreased Aß accumulation using 6E10 antibody. Furthermore, Aß1-42 induced strong autophagy response, however ICA decreased the levels of microtubule-associated protein 1 light chain 3 (LC3) II/LC3I, Beclin1, Cathepsin D (Cat D) and brain lysosomal Cathepsin D activity. We also observed that ICA enhanced the phosphorylation of protein kinase B (PKB/AKT) and p70 ribosomal protein S6 kinase (p70S6K). In addition, ICA arrested Aß1-42-induced cells loss, mitochondrias damage, nuclear membranes unclear and abundant nucleas chromatin agglutinates in hippocampus, lessened the expression of Cleaved-caspase-3, brain oxidative stress, astroglial activation. These findings suggest that ICA can ameliorate amyloid pathologies with improving autophagy-lysosome function and Chinese materia medica may be potential for AD treatment.

Electroacupuncture for Functional Constipation: A Multicenter, Randomized, Control Trial.

Background and Aim. To investigate the efficacy and safety of electroacupuncture (EA) with different current intensities for functional constipation (FC) and to assess whether the effects of EA with different current intensities are superior to the mosapride. Methods. Patients with FC were randomly divided into low current intensity group (LCI), high current intensity group (HCI), and mosapride group (MC). The primary outcome was three or more spontaneous bowel movements (SBMs) per week and an increase of one or more SBMs from baseline during at least 3 of the 4 weeks. Results. The primary outcome was reached by 53.45%, 66.15%, and 52.24% of the patients who received LCI, HCI, and mosapride, respectively. EA can significantly improve the weekly SBMs and stool consistency and reduce straining severity (p < 0.0001, all). HCI improved the quality of life better than mosapride (p < 0.05) and reduced the proportion of severe constipation more than LCI and mosapride (p < 0.05, both). Conclusions. EA is effective and safe at both current intensities for FC; therapeutic effects of LCI and HCI are not superior to mosapride. EA is superior to mosapride in improving patients' life quality and satisfaction level of treatment; EA has fewer adverse events than mosapride.

Metatranscriptomic discovery of plant biomass-degrading capacity from grass carp intestinal microbiomes.

Despite the economic importance of fish, the ecology and metabolic capacity of fish microbiomes are largely unknown. Here, we sequenced the metatranscriptome of the intestinal microbiota of grass carp, Ctenopharyngodon idellus, a freshwater herbivorous fish species. Our results confirmed previous work describing the bacterial composition of the microbiota at the phylum level as being dominated by Firmicutes, Fusobacteria, Proteobacteria and Bacteriodetes. Comparative transcriptomes of the microbiomes of fish fed with different experimental diets indicated that the bacterial transcriptomes are influenced by host diet. Although hydrolases and cellulosome-based systems predicted to be involved in degradation of the main chain of cellulose, xylan, mannan and pectin were identified, transcripts with glycoside hydrolase modules targeting the side chains of noncellulosic polysaccharides were more abundant. Predominant 'COG' (Clusters of Orthologous Group) categories in the intestinal microbiome included those for energy production and conversion, as well as carbohydrate and amino acid transport and metabolism. These results suggest that the grass carp intestinal microbiome functions in carbohydrate turnover and fermentation, which likely provides energy for both host and microbiota. Grass carp intestinal microbiome thus reflects its evolutionary adaption for harvesting nutrients for an herbivore with a high-throughput nutritional strategy that is not dominated by cellulose digestion but rather the degradation of intracellular polysaccharides.

Effects of acupuncture on progesterone and prolactin in rats of embryo implantation dysfunction.

OBJECTIVE: To investigate the effect of acupuncture on progesterone (P4) and prolactin (PRL) in rats of embryo implantation dysfunction (EID). METHODS: On the first day of pregnancy, 72 female Wistar rats were randomly allocated into the normal group, the EID model group, the acupuncture group and the P4 group (18 in each group). The normal group was injected sesame oil, while the other three groups were given mifepristone to establish the EID model. The acupuncture group and the P4 group were given treatment of acupuncture and P4 injection, respectively. The serum of P4 and PRL were detected by radioimmunoassay, and the mRNA and protein expressions of P4 receptor (PR) and PRL receptor (PRLR) were detected using real-time polymerase chain reaction and immunohistochemical method, respectively. RESULTS: Compared with the normal group, the serum levels of P4 and PRL as well as the mRNA and protein expression levels of PR and PRLR in the EID model group were significantly lowered (P<0.01 or P<0.05). The above indices in the acupuncture group and the P4 group were significantly elevated compared with the EID model group (P<0.01 or P<0.05). CONCLUSION: Acupuncture can promote embryo implantation effectively, which might be related to the effects of acupuncture on upregulating the P4 and PRL levels in serum and the PR and PRLR expression levels in rats.

Clinical study of electro-acupuncture treatment with different intensities for functional constipation patients.

Functional constipation (FC) is a common functional bowel disorder disease that affects life quality of a large number of people. This study aimed to explore the impact of different intensities of electro-acupuncture (EA) treatment for FC patients. Totally, 111 patients with FC meeting the Rome III criteria were randomly assigned to different intensities of EA groups (low and high intensity of EA groups) and medicine-controlled (MC) group. In EA groups, patients were treated with EA at quchi (LI11) and shangjuxu (ST37) bilaterally for 4 weeks, 5 times/week in the first 2 weeks, and 3 times/week in the last 2 weeks. In MC group, 5 mg mosapride citrate was administered orally 3 times/day for 4 weeks. Spontaneous bowel movement frequency each day was recorded using a constipation diary. Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used to assess the patients' psychological state. Cortisol (CORT), substance P (SP), and vasoactive intestinal polypeptide (VIP) were evaluated at baseline and at the end of 4 weeks after treatment. As compared with the baseline, there was statistically significant increase in stool frequency every week (P<0.01), but there was no statistically significant difference among the three groups. As compared with the baseline, after 4 weeks of EA therapy, the scores of SDS and serum levels of CORT were decreased significantly in low intensity of EA group (P<0.01), and the serum levels of SP and VIP were increased significantly (P<0.05); the scores of SAS and SDS and serum levels of CORT were decreased significantly in high intensity of EA group (P<0.05), and the serum levels of SP and VIP were increased significantly (P<0.05); the serum levels of CORT and VIP were increased significantly in MC group (P<0.05). As compared with MC group, after 4 weeks of treatment, the serum levels of SP were signifcicantly increased in low intensity of EA group (P<0.01). Low and high intensities of EA could increase the stool frequency, improve the FC patient's anxiety and depression, reduce the serum levels of CORT, and increase the serum levels of SP and VIP effectively. It is concluded that both low and high intensities of EA are effective for FC patients, but there is no significant difference between the low and high intensities of EA.

Effects of acupuncture on Th1, th2 cytokines in rats of implantation failure.

The aim is to explore the effect of acupuncture on Th1, Th2 cytokines in rats of implantation failure. Early pregnant rats were randomized into normal group (N), implantation failure group (M), acupuncture group (A), progestin group (H). The model was established with mifepristone. Samples of serum, endometrium were collected on Day 5, 6 and 8 of pregnancy. Compared with group M, the number of embryos was significantly higher in groups N, A and H; IL-1ß, IL-2 protein in serum and endometrium were significantly lower in groups N, A and H, while IL-4, IL-10 were significantly higher in groups N, A and H; the endometrial IL-2, IL-4 mRNA were significantly lower in groups N, A and H, while IL-1ß, IL-10 mRNA were significantly higher in groups N, A and H. Acupuncture could improve the poor receptive state of endometrium due to mifepristone by promoting Th2 cytokines secretion and inhibiting Th1 cytokines to improve blastocyst implantation.

Effects of acupuncture on LIF and IL-12 in rats of implantation failure.

PROBLEM: Acupuncture has a positive effect on implantation obstacle, but the mechanism is still not clear, so the aim of the experiment is to explore the possible role that acupuncture plays in implantation. METHOD OF STUDY: Early pregnant rats were randomized into normal group (N), group treated with mifepristone (M), acupuncture treatment group (A), and progestin treatment group (P). The model of blastocyst implantation obstacle in groups M, A, and P was established with mifepristone. Bilateral 'Housanli' and 'Sanyinjiao' were needled in group A. The expression of interleukin (IL)-12, leukemia inhibitory factor (LIF), LIFR protein, and mRNA in endometrium were detected. RESULTS: Positivity of the protein expression of IL-12, LIF, and LIFR in the endometrium was significantly higher in groups N, A, and P; positivity of the mRNA of IL-12 and LIF in the endometrium was significantly higher in groups N, A, and P. CONCLUSION: Acupuncture could improve the poor receptive state of endometrium by promoting LIF and IL-12 secretion to improve blastocyst implantation.