Mechanisms underlying the therapeutic effects of Semen cuscutae in treating recurrent spontaneous abortion based on network pharmacology and molecular docking.

Background: This paper aims to analyse the active components of Semen cuscutae (SC) by network pharmacology and screen the most stable compounds with tumour necrosis factor-alpha (TNF-α) by molecular docking to explore the mechanisms of SC treatment of recurrent spontaneous abortion (RSA) and provide a theoretical basis for drug development. Methods: The active compounds of SC and the potential inflammatory targets of RSA were obtained from the Traditional Chinese Medicine Systems Pharmacology database and GeneCards, respectively. The RSA-SC target gene interaction network was obtained and visualized using the STRING database and Cytoscape software. GO and KEGG pathway enrichment analyses were obtained from DAVID to further explore the RSA mechanism and therapeutic effects of SC. Interactions between TNF-α and drugs were analysed by molecular docking. Treatment of human trophoblast cells with sesamin and TNF-α was carried out to detect their proliferative and apoptotic abilities, and WB assay was carried out to detect EGFR, PTGS2, and CASP3 protein expression. Results: Ten compounds and 128 target genes were screened from SC, of which 79 overlapped with RSA target inflammatory genes, which were considered potential therapeutic targets. Network pharmacological analysis showed that sesamin, matrine, matrol, and other SC compounds had a good correlation with the inflammatory target genes of RSA. Related genes included PGR, PTGS1, PTGS2, TGFB1, and CHRNA7. Several signalling pathways are involved in the pathogenesis of RSA, such as the TNF-α signalling pathway, HIF-1 signalling pathway, oestrogen signalling pathway, proteoglycans in cancer cells, and FoxO signalling pathway. Molecular docking results suggested that sesamin was the most suitable natural tumour necrosis factor inhibitor (TNFi). Sesamin can promote proliferation and inhibit apoptosis in human trophoblasts by downregulating EGFR and CASP3 expression and upregulating PTGS2 expression. Conclusion: Our findings play an important role and basis for further research into the molecular mechanism of SC treatment of RSA and drug development of TNFi.

Association of LncRNA PCBP1-AS1 with cancer occurrence and development: A review.

Long-stranded noncoding RNAs (LncRNAs) are noncoding RNAs >200 nucleotides in length. Polycytidine binding protein 1 antisense LncRNA is abbreviated as LncRNA polycytosine binding protein 1 antisense1 (PCBP1-AS1). Since studies in recent years have revealed the importance of PCBP1-AS1 in human genetic analysis, it is an important member of the LncRNA family. Genetically engineered group analysis of PCBP1-AS1 regulates the progression of cancer in biology. Therefore, it may be an important RNA in the regulation of human cancer. This article summarizes the molecular mechanism and clinical role of PCBP1-AS1 in various tumor types. Taking "PCBP1-AS1" and "cancer" as keywords, this paper analyzed the relationship between PCBP1-AS1 and various tumors by searching PubMed and Geen Medical, and summarized the related regulatory mechanism of PCBP1-AS1. PCBP1-AS1 is a valuable tumor-associated LncRNA that plays different biological roles in different cancers. Overall, it can both promote and inhibit the development of cancer. For example, abnormally high expression in castration-resitant prostate cancer, hepatocellular carcinoma, cervical cancer, glioma, and colorectal cancer promotes the proliferation and progression of these cancers; in contrast, PCBP1-AS1 inhibits cancer proliferation, metastasis, invasion, and recurrence when highly expressed in vulvar squamous cell carcinoma, Hodgkin lymphoma, and lung adenocarcinoma. PCBP1-AS1 regulates the development of multiple tumors, and the specific mechanism needs to be further investigated, which may become a new tumor marker and potential therapeutic target.

Identifying subgroups of patients with type 2 diabetes based on real-world traditional chinese medicine electronic medical records.

Introduction: Type 2 diabetes (T2D) is a multifactorial complex chronic disease with a high prevalence worldwide, and Type 2 diabetes patients with different comorbidities often present multiple phenotypes in the clinic. Thus, there is a pressing need to improve understanding of the complexity of the clinical Type 2 diabetes population to help identify more accurate disease subtypes for personalized treatment. Methods: Here, utilizing the traditional Chinese medicine (TCM) clinical electronic medical records (EMRs) of 2137 Type 2 diabetes inpatients, we followed a heterogeneous medical record network (HEMnet) framework to construct heterogeneous medical record networks by integrating the clinical features from the electronic medical records, molecular interaction networks and domain knowledge. Results: Of the 2137 Type 2 diabetes patients, 1347 were male (63.03%), and 790 were female (36.97%). Using the HEMnet method, we obtained eight non-overlapping patient subgroups. For example, in H3, Poria, Astragali Radix, Glycyrrhizae Radix et Rhizoma, Cinnamomi Ramulus, and Liriopes Radix were identified as significant botanical drugs. Cardiovascular diseases (CVDs) were found to be significant comorbidities. Furthermore, enrichment analysis showed that there were six overlapping pathways and eight overlapping Gene Ontology terms among the herbs, comorbidities, and Type 2 diabetes in H3. Discussion: Our results demonstrate that identification of the Type 2 diabetes subgroup based on the HEMnet method can provide important guidance for the clinical use of herbal prescriptions and that this method can be used for other complex diseases.

AQP4 Aggravates Cognitive Impairment in Sepsis-Associated Encephalopathy through Inhibiting Nav 1.6-Mediated Astrocyte Autophagy.

The pathology of sepsis-associated encephalopathy (SAE) is related to astrocyte-inflammation associated with aquaporin-4 (AQP4). The aim here is to investigate the effects of AQP4 associated with SAE and reveal its underlying mechanism causing cognitive impairment. The in vivo experimental results reveal that AQP4 in peripheral blood of patients with SAE is up-regulated, also the cortical and hippocampal tissue of cecal ligation and perforation (CLP) mouse brain has significant rise in AQP4. Furthermore, the data suggest that AQP4 deletion could attenuate learning and memory impairment, attributing to activation of astrocytic autophagy, inactivation of astrocyte and downregulate the expression of proinflammatory cytokines induced by CLP or lipopolysaccharide (LPS). Furthermore, the activation effect of AQP4 knockout on CLP or LPS-induced PPAR-γ inhibiting in astrocyte is related to intracellular Ca2+ level and sodium channel activity. Learning and memory impairment in SAE mouse model are attenuated by AQP4 knockout through activating autophagy, inhibiting neuroinflammation leading to neuroprotection via down-regulation of Nav 1.6 channels in the astrocytes. This results in the reduction of Ca2+ accumulation in the cell cytosol furthermore activating the inhibition of PPAR-γ signal transduction pathway in astrocytes.

Klebsiella pneumoniae liver abscess with purulent meningitis and endogenous endophthalmitis: A case report.

This is a rare but typical case of a Klebsiella pneumoniae liver abscess with migratory infections including purulent meningitis and endogenous endophthalmitis. The patient had a chief complaint of 7 days of fever, 4 days of blurry vision, and 4 h of glossolalia. Ultrasound scan and computed tomography (CT) suggested a liver abscess. Both blood and drainage fluid cultures grew K. pneumoniae with a high mucosal phenotype. The patient was finally diagnosed with a K. pneumoniae liver abscess, purulent meningitis, and endogenous K. pneumoniae endophthalmitis in the right eye. Ultrasound-guided percutaneous catheter drainage (PCD) of the liver abscess was performed, and meropenem was used to control infection. The patient was given 0.1 ml of vancomycin (10 g/L) and 0.1 ml of ceftazidime (20 g/L) were by intravitreal injection for the treatment of endophthalmitis. The infection was gradually controlled after such treatments. The patient was discharged from our hospital with an improved condition. However, during the time of follow-up, she developed complications due to severe pneumonia and eventually died in a local hospital. This case revealed that a rapid diagnosis followed by appropriate treatment would improve prognosis and prevent severe metastatic complications.

Identification of immunity- and ferroptosis-related genes for predicting the prognosis of serous ovarian cancer.

BACKGROUND: Serous ovarian cancer (SOC) is the most common type of ovarian cancer (OC), with bad outcomes. To improve the prognosis of SOC patients, a novel risk signature was developed by combining immunity- and ferroptosis-related genes. METHODS: By means of comparing SOC tissues with normal tissues, we screened the differential expression of immunity-related genes (DE-IRGs) and ferroptosis-related genes(DE-FRGs) with the standards of |log2fold change| > 1 and false discovery rate (FDR) < 0.05. After obtaining the meaningful differentially expressed genes from immune and ferroptosis (DEGs), we established a prognostic risk signature by utilizing Cox regression analyses in TCGA training set, which was validated in TCGA testing set and GSE26712 dataset. Besides, the differential expression of immune-related markers, immunophenoscore (IPS), TIDE score,T cell dysfunction score and T cell exclusion score were also analyzed. We further verified the expression of target genes in ovarian tumor cells lines by QRT-PCR. RESULTS: A risk signature constructed by totally four immunity- and ferroptosis-related DEGs (CXCL11, CX3CR1, FH, and DNAJB6) was developed, which distinguished the SOC patients as high-risk and low-risk groups. Patients in the high-risk group showed a lower overall survival (OS) than those in the low-risk group. Furthermore, the risk score was independent when analyzed with clinical augments, which was significantly associated with 13 KEGG signaling pathways. The gene signature showed favorable predictive performance according to Receiver operating characteristic (ROC) curves. Notably, the expression of immune-related markers or IPS indicated a negative connection with the risk score. SOC patients had a lower score of TIDE and T cell dysfunction than Whom had a higher score. Nonetheless, there were no significant differences in T cell exclusion scores between the two groups.Compared with normal ovarian cell line IOSE-80,QRT-PCR experiments exhibited that CXCL11, CX3CR1and FH were up-regulated in ovarian tumor cells lines(SK-OV-3,COC1,A2780),while DNAJB6 was down-regulated. CONCLUSION: Four-biomarker signature formed by immunity- and ferroptosis-related genes may be clinically used as risk stratifcation tool in serous ovarian cancer,which can help further clinical decision-making regarding prognostic prediction,individualized treatment and follow-up scheduling.

miR-146a-5p-mediated suppression on trophoblast cell progression and epithelial-mesenchymal transition in preeclampsia.

OBJECTIVE: This study aims to identify the effect of miR-146a-5p on trophoblast cell invasion as well as the mechanism in preeclampsia (PE). METHODS: Expression levels of miR-146a-5p and Wnt2 in preeclamptic and normal placentae were quantified. Trophoblast cells (HTR-8) were separately transfected with miR-146a-5p mimic, miR-146a-5p inhibitor, pcDNA3.1-Wnt2 or sh-Wnt2, and then the expression levels of miR-146a-5p, Wnt2, and epithelial-mesenchymal transition (EMT)-related proteins (Vimentin, N-cadherin and E-cadherin) were measured. Moreover, the proliferative, migratory and invasive capacities of trophoblast cells were detected, respectively. Dual luciferase reporter assay determined the binding of miR-146a-5p and Wnt2. RESULTS: Compared with normal placental tissues, the placentae from PE patients showed higher miR-146a-5p expression and lower Wnt2 expression. Transfection of miR-146a-5p inhibitor or pcDNA3.1-Wnt2 exerted pro-migratory and pro-invasive effects on HTR-8 cells and encouraged EMT in HTR-8 cells; transfection with miR-146a-5p mimic or sh-Wnt2 weakened the proliferative, migratory and invasive capacities as well as reduced EMT process of HTR-8 cells. Moreover, Wnt2 overexpression could partially counteract the suppressive effects of miR-146a-5p overexpression on the progression and EMT of HTR-8 cells. CONCLUSION: miR-146a-5p mediates trophoblast cell proliferation and invasion through regulating Wnt2 expression.

miR-146a-5p-mediated suppression on trophoblast cell progression and epithelial-mesenchymal transition in preeclampsia

OBJECTIVE: This study aims to identify the effect of miR-146a-5p on trophoblast cell invasion as well as the mechanism in preeclampsia (PE). METHODS: Expression levels of miR-146a-5p and Wnt2 in preeclamptic and normal placentae were quantified. Trophoblast cells (HTR-8) were separately transfected with miR-146a-5p mimic, miR-146a-5p inhibitor, pcDNA3.1-Wnt2 or sh-Wnt2, and then the expression levels of miR-146a-5p, Wnt2, and epithelial-mesenchymal transition (EMT)-related proteins (Vimentin, N-cadherin and E-cadherin) were measured. Moreover, the proliferative, migratory and invasive capacities of trophoblast cells were detected, respectively. Dual luciferase reporter assay determined the binding of miR-146a-5p and Wnt2. RESULTS: Compared with normal placental tissues, the placentae from PE patients showed higher miR-146a-5p expression and lower Wnt2 expression. Transfection of miR-146a-5p inhibitor or pcDNA3.1-Wnt2 exerted pro-migratory and pro-invasive effects on HTR-8 cells and encouraged EMT in HTR-8 cells; transfection with miR-146a-5p mimic or sh-Wnt2 weakened the proliferative, migratory and invasive capacities as well as reduced EMT process of HTR-8 cells. Moreover, Wnt2 overexpression could partially counteract the suppressive effects of miR-146a-5p overexpression on the progression and EMT of HTR-8 cells. CONCLUSION: miR-146a-5p mediates trophoblast cell proliferation and invasion through regulating Wnt2 expression.

MicroRNA-27a inhibits trophoblast cell migration and invasion by targeting SMAD2: Potential role in preeclampsia.

Preeclampsia (PE) is a severe idiopathic obstetric complication that occurs worldwide. Insufficient trophoblast invasion is a characteristic of the pathogenesis of PE. MicroRNA-27a (miR-27a) has been reported to be highly expressed in PE placentas. The aim of the present study was to investigate the role and underlying mechanisms of miR-27a in the pathogenesis of PE. The expression level of miR-27a was evaluated in the placenta and serum from patients with PE and healthy pregnant women. Cell Counting Kit-8 and flow cytometry assays were performed to detect human HTR-8/SVneo trophoblast proliferation and apoptosis after miR-27a overexpression or inhibition. In addition, Transwell assays were used to measure cell migration and invasion. A luciferase reporter assay was performed to determine the interaction between miR-27a and SMAD2. The present results suggested that miR-27a expression level was significantly increased in PE placentas and serum. In addition, miR-27a overexpression suppressed cell migratory and invasive abilities, impaired proliferation and promoted apoptosis in human trophoblasts. It was demonstrated that miR-27a may target SMAD and contribute to trophoblast invasion. Collectively, the results of the present study suggested that miR-27a inhibited trophoblast cell migration and invasion by targeting SMAD2, thus presenting a promising therapeutic target for PE.

Diagnostic value of neutrophil-lymphocyte ratio in preeclampsia: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Neutrophil-lymphocyte ratio (NLR) is one of the markers of systemic inflammation. Recent studies have associated NLR with diagnosis of preeclampsia (PE). However, due to small sample sizes and different research design, the diagnostic value of NLR in PE patients is not well understood. In this study, we evaluate the potential diagnostic value of NLR in PE. METHODS: We searched PubMed, Embase, Cochrane Library, the Chinese National Knowledge Infrastructure (CNKI) databases, Wanfang data, VIP database and China Biomedical Literature Database systematically for relevant literatures up to May 20, 2018. All analyses were conducted using Meta-DiSc1.4 and Stata 12.0 software. Sensitivity, specificity and other measures of accuracy of NLR for the diagnosis of PE were pooled. Meta-regression was performed to identify the sources of heterogeneity. RESULTS: This meta-analysis included a total of 7 studies. The pooled sensitivity and specificity were 0.74 (95% CI 0.71-0.76) and 0.64 (95%CI 0.61-0.68), positive likelihood ratio, 2.62 (95%CI1.79-3.84); negative likelihood ratio, 0.34 (95%CI 0.24-0.48); diagnostic odds ratio, 8.44 (95%CI 4-17.78), and area under the curve was 0.82. Meta regression showed that sample size was the main source of heterogeneity. Deeks funnel plot showed that there was no statistical significance for the evaluation of publication bias (P = .16). CONCLUSION: Current evidence suggests that the diagnostic accuracy of NLR has unsatisfactory specificity but acceptable sensitivity for diagnosis of PE. Further large-scale prospective studies are required to validate the potential applicability of using NLR alone or in combination other markers as PE diagnostic biomarker and explore potential factors that may influence the accuracy of NLR for PE diagnosis.

Motor Neuron and Pancreas Homeobox 1 (MNX1) Is Involved in Promoting Squamous Cervical Cancer Proliferation via Regulating Cyclin E.

BACKGROUND Cervical cancer is one of the most lethal gynecologic malignancies worldwide. The objective of this study was to assess the role of MNX1 in cervical cancer and its underlying mechanisms. MATERIAL AND METHODS The expression of motor neuron and pancreas homeobox 1 (MNX1) in immortal epithelial cervical cell line ECT, cervical cancer cell HeLa, and SiHa and cervical cancer, as well as in adjacent noncancer tissues, was detected and analyzed. CCK-8 and colony formation assays were performed to evaluate the effects of MNX1 overexpression on cervical cancer cell proliferation. Transwell assay was used to detect migration and invasion after MNX1 knockdown or overexpression. Real-time PCR and Western blotting were used to examine MNX1 and cell cycle regulator expression. RESULTS Data from our study indicated that MNX1 was upregulated both in cervical cancer cell lines and cervical cancer tissues. The high levels of MNX1 are related to advanced stages and lymph nodes metastasis. The overexpression of MNX1 promoted cervical cancer cells proliferation, migration, and invasion. Moreover, MNX1 upregulated 2 critical cell cycle regulators, CCNE1 and CCNE2. CONCLUSIONS These findings reveal MNX1 as a novel oncogene of cervical cancer and indicate MNX1 is a promising therapeutic and prognostic biomarker.

Circulating Cell Free DNA as the Diagnostic Marker for Ovarian Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Quantitative analyses of circulating cell-free DNA (cfDNA) are potential methods for the detection of ovarian cancer. Many studies have evaluated these approaches, but the results were too inconsistent to be conclusive. This study is the first to systematically evaluate the accuracy of circulating cfDNA for the diagnosis of ovarian cancer by conducting meta-analysis. METHODS: We searched PubMed, Embase, Cochrane Library and the Chinese National Knowledge Infrastructure (CNKI) databases systematically for relevant literatures up to December 10, 2015. All analyses were conducted using Meta-DiSc1.4 and Stata 12.0 software. Sensitivity, specificity and other measures of accuracy of circulating cfDNA for the diagnosis of ovarian cancer were pooled. Meta-regression was performed to identify the sources of heterogeneity. RESULTS: This meta-analysis included a total of 9 studies, including 462 ovarian cancer patients and 407 controls. The summary estimates for quantitative analysis of circulating cfDNA in ovarian cancer screen were as follows: sensitivity, 0.70 (95% confidence interval (CI), 0.65-0.74); specificity, 0.90 (95% CI, 0.87-0.93); positive likelihood ratio, 6.60 (95% CI, 3.90-11.17); negative likelihood ratio, 0.34 (95% CI, 0.25-0.47); diagnostic odds ratio, 26.05 (95% CI, 14.67-46.26); and area under the curve, 0.89 (95% CI, 0.83-0.95), respectively. There was no statistical significance for the evaluation of publication bias. CONCLUSIONS: Current evidence suggests that quantitative analysis of cfDNA has unsatisfactory sensitivity but acceptable specificity for the diagnosis of ovarian cancer. Further large-scale prospective studies are required to validate the potential applicability of using circulating cfDNA alone or in combination with conventional markers as diagnostic biomarker for ovarian cancer and explore potential factors that may influence the accuracy of ovarian cancer diagnosis.