Purpose. To discuss the effects of dydrogesterone combined with letrozole on the effectiveness, sex hormone levels, and serological indicators in patients with endometriosis. This study is registered with PROSPERO (CRD42020213172). Methods. We searched relevant randomized controlled trials (RCTs) through PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP Database. The standardized mean differences (SMDs), the mean differences (MDs), or odds ratios (ORs) with their 95% confidence intervals (95% CIs) were computed to be outcome indicators, including total effectiveness, Vascular Endothelial Growth Factor (VEGF) level, Carbohydrate Antigen 125 (CA125) level, Follicle-Stimulating Hormone (FSH) level, Luteinizing Hormone (LH) level, estrogen (E2) level, progesterone (P) level, interleukin-6 (IL-6) level, and tumor necrosis factor-a (TNF-a) level. Results. A total of 19 RCTs involving 1,591 patients were included in this study. Our results showed that letrozole combined with dydrogesterone can significantly reduce the levels of VEGF (SMD -2.23, 95% CI -2.39 to -2.07; p < 0.00001 ), CA125 (MD -10.53, 95% CI -11.19 to -9.88; p < 0.00001 ), E2 (SMD -1.64, 95% CI -1.81 to -1.47; p < 0.00001 ), P (MD -5.11, 95% CI -6.26 to -3.96; p < 0.00001 ), IL-6 (MD -4.41, 95% CI -5.16 to -3.67; p < 0.00001 ), and TNF-a (MD -5.67, 95% CI -6.34 to -5.00; p < 0.00001 ) in patients with endometriosis compared with the control group. In addition, the results indicated that total effectiveness was significantly higher in the experiment group (OR 6.21, 95% CI 4.17 to 9.24; p < 0.00001 ) compared to the control. However, there was no significant difference between FSH and LH levels in both groups ( p > 0.05 ). Conclusion. This combination therapy can effectively decrease the levels of VEGF, CA125, E2, P, IL-6, and TNF-a and increase the total effectiveness when comparing with the control group.

Ethnopharmacological Relevance. Gegen Qinlian decoction (GGQLD) is an effective formula treatment for rotavirus enteritis (RVE), which has been applied for 1900 years. It consists of 4 herbal medicines corresponding to the four roles “monarch, minister, assistant, and guide,” which is the basic rule of prescription composition in traditional Chinese medicine (TCM). However, its active ingredients and therapeutic mechanism on RVE have not been fully investigated. Materials and Methods. In this study, a network pharmacology-based strategy was used to elucidate the mechanism of GGQLD for the treatment of RVE. Oral bioavailability and drug-likeness were taken as the judgment criteria to search the active ingredients of GGQLD in traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). The affinity between protein and ingredients was further determined using the similarity ensemble approach to find the corresponding targets. According to the genes related to enteritis in GeneCards database, the key targets were screened by intersections between drug and disease targets. And the therapeutic mechanism was predicted using the protein-protein interactions (PPIs), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, which was verified by detecting calcium ion concentration with the fluorescent probe. Result. 130 active ingredients were screened from GGQLD, including (R)-canadine, moupinamide, formononetin, and other flavonoids. They act on a total of 366 targets, which is mainly distributed in the biological process of hormone binding or signaling pathways of neuroactive ligand receptor interaction, serotonergic synapse, and calcium signaling pathway. Furthermore, serotonin receptors, adrenergic receptors, cholinergic receptors, and dopamine receptors in the enteric nervous system may be the key targets of RVE treatment by GGQLD. Conclusion. This study demonstrated that the potential mechanism that GGQLD can effectively improve the symptoms of RVE may depend on the regulation of calcium ions, serotonin, and gastrointestinal hormone ion that could mutually affect the intestinal nervous system.

No abstract

To investigate the role of miR-4301 in rotavirus (RV)-infected Caco-2 cells. In this experiment, RNAs of RV-infected Caco-2 cells were extracted, and the highthroughput second-generation sequencing was performed to detect the expression profiles of host microRNAs (miRNAs). Synthetic miRNA mimics and inhibitors were examined (quantitative polymerase chain reaction [qPCR], crystalline violet, immunofluorescence and electron microscopy) to evaluate the effect on RV replication. Target genes of miR-4301 were predicted by software analysis. The expression of target genes was evaluated by qPCR and Western blot after transfected with miRNA inhibitor/mimic, and crystalline violet and qPCR were used to detect the downregulation effects of target genes on RV replication. By transfecting miRNA inhibitors/mimics and detecting downstream target genes, the mechanism of miRNA affecting RV replication was analyzed. There were 78 known miRNAs with significant differential expression, including 39 upregulated miRNAs and 39 downregulated miRNAs. The results showed that miR-4301 exerted a key role in enhancing RV replication. PPP1R3D protein which can inhibit RV replication was predicted as the target gene of miR-4301 by software analysis.While upregulating miR-4301 by RV, the expression of PPP1R3D and glycogen synthase (GS) is suppressed. For the first time, the effect of miR-4301 on RV infection, and its influence on GS was investigated. Specifically, RV inhibits host cell glycogen synthesis to utilize the host intracellular glucose for promoting its own replication.

Viruses have evolved mechanisms to usurp the host's metabolic resources for their own biosynthesis and replication, but host's glucose metabolism change after rotavirus (RV) stress remains unclear. The metabolic profile and differential gluconeogenesis analysis was performed by gas chromatography-mass spectroscopy on RV-infected cells.47 potential differential metabolites were identified to verify glycolytic/gluconeogenesis pathway after RV infection. Glucose consumption and key enzymes of gluconeogenesis (glucose 6-phosphatase (G-6-pase) and phosphoenolpyruvate carboxylase (PEPCK)) were further examined by glucose oxidase-peroxidase method and enzyme linked immunosorbent assay. We found the impairment of glucose consumption, G-6-pase and PEPCK activities which promote gluconeogenesis, were tested in RV infected Caco-2 cells. By Western blot analysis, further studies detected the downregulation expression level of SIK2, which was affected by its upstream proteins of downregulated PDK1, AKT and upregulation p-JNK, and as a consequence influenced the function of gluconeogenesis. In short, RV infection altered the glucose consumption in infectious Caco-2 cells and activated the host cellular gluconeogenesis, which was hijacked through p-JNK-PDK1-AKT-SIK2 signaling pathway for its proliferation and replication with accelerating non-sugar substances conversion into glucose.