Explore the vast range of titles available.

The epithelial-mesenchymal transition (EMT) is crucial to cancer progression and metastasis. Although multiple cellular miRNAs have been identified to regulate the EMT and metastasis in cancers, the role of viral miRNAs in cancer progression remains largely unknown. Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy typically characterized by its early metastasis. In the present study, we have discovered the involvement of a viral miRNA, EBV-miR-BART7-3p, in the EMT and metastasis of NPC cells. Initially, we observed that EBV-miR-BART7-3p was highly expressed in NPC and positively correlated with lymph node metastasis and clinical stage of NPC. Subsequently, we demonstrated that EBV-miR-BART7-3p enhanced cell migration/invasion in vitro , cancer metastasis in vivo , and particularly the EMT characterized by loss of epithelial markers and gain of mesenchymal features in NPC cells. Furthermore, mechanistic studies disclosed that EBV-miR-BART7-3p targeted a major human tumor suppressor PTEN, modulating PI3K/Akt/GSK-3β signaling and eventually leading to the high expression and nuclear accumulation of Snail and β-catenin, which favor EMT. Knockdown of PTEN could phenocopy the effect of EBV-miR-BART7-3p, whereas re-expression of PTEN resulted in a phenotypic reversion. Moreover, these findings were supported by an observation of an EBV-positive cell model in which silencing of endogenous EBV-miR-BART7-3p partially attenuated cell migration/invasion and altered EMT protein expression pattern via reverting PI3K/Akt, Snail and β-catenin expression. Thus, this study suggests a novel mechanism by which EBV-miR-BART7-3p modulates the EMT and metastasis of NPC cells, and a clinical implication of EBV-miR-BART7-3p as a potential biomarker or therapeutic target.

Transition metals can catalyse the stereoselective synthesis of cyclic organic molecules in a highly atom-efficient process called cycloisomerization. Many diastereoselective (substrate stereocontrol), and enantioselective (catalyst stereocontrol) cycloisomerizations have been developed. However, asymmetric cycloisomerizations where a chiral catalyst specifies the stereochemical outcome of the cyclization of a single enantiomer substrate—regardless of its inherent preference—are unknown. Here we show how a combined theoretical and experimental approach enables the design of a highly reactive rhodium catalyst for the stereoselective cycloisomerization of ynamide-vinylcyclopropanes to [5.3.0]-azabicycles. We first establish highly diastereoselective cycloisomerizations using an achiral catalyst, and then explore phosphoramidite-complexed rhodium catalysts in the enantioselective variant, where theoretical investigations uncover an unexpected reaction pathway in which the electronic structure of the phosphoramidite dramatically influences reaction rate and enantioselectivity. A marked enhancement of both is observed using the optimal theory-designed ligand, which enables double stereodifferentiating cycloisomerizations in both matched and mismatched catalyst–substrate settings. Using a chiral catalyst to override the innate stereochemical outcome of a diastereoselective process is a challenging task. Here, the authors use theory and experiment to develop a cycloisomerization where the enantioselectivity is driven by the electronic nature of the ligand regardless of the reaction's inherent diastereoselectivity.

We studied the effect of acteoside on a model of human corneal epithelial cells (HCEC) injury induced by H 2 O 2 . HCEC were divided into 4 groups and cultured for 24 h in normal medium (intact and control groups, respectively), or in a medium containing DMSO or 160 μM acteoside (DMSO and acteoside groups, respectively). Then, H 2 O 2 solution was added to HCEC for 4 h, except for intact cells. The cell viability was assessed by the CCK8 method to determine the working concentrations of acteoside and H 2 O 2 for further experiments. Quantitative PCR and Western blotting were used to determine the effect of acteoside and H 2 O 2 on the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NADPH:quinone oxidoreductase-1 (NQO-1), and cyclooxygenase-2 (COX-2). The effects of these agents on cell proliferation were assessed by staining with 5-ethynyl-2'-deoxyuridine (EdU). It was found that acteoside protected HCEC against H 2 O 2 -induced damage by inhibiting the expression of Nrf2, HO-1, NQO-1, and COX-2.

Background The aim of this study was to provide information on the semen quality pattern of infertile men and age thresholds for semen parameters in China. Methods This was a retrospective cross-sectional study investigating 71,623 infertile men from the Reproductive and Genetic Hospital of CITIC Xiangya in Hunan, China, from 2011 to 2017. The Kruskal-Wallis test, Mann-Kendall test, linear regression model and joinpoint regression were used. Results Although erratic changes were observed in the median semen parameters (sperm concentration 40.1–52.1 × 10 6 /ml, total sperm count 117.8–153.1 × 10 6 , sperm progressive motility 33.4–38.1%) during the 7 years of observation, no significant decrease in semen quality was found, and 47.88% of infertile men showed normal semen parameters according to the World Health Organization (WHO) criteria. According to the joinpoint regression analysis, sperm progressive motility appeared to decrease earlier than the sperm concentration and total sperm count (at 28, 58, and 42 years of age, respectively). Conclusions There is no evidence of a deterioration in semen quality among infertile men in Hunan, China. Semen parameters decreased with increasing age, with turning points noted at different ages. Semen parameters are not absolute evidence for the assessment of male fertility potential. Therefore, we believe that, among semen parameters, the sperm concentration is the best predictor of fertility for ART, followed by motility. Decreased sperm motility may affect natural pregnancy, but it is not necessary for successful IVF.

Preliminary studies showed that miR-21 is overexpressed in some human cancers. However, the role of miR-21 in cancer is still unclear and even controversial. Our purpose was to investigate the biological effects of miR-21 on A549 non-small cell lung cancer (NSCLC) cells and the underlying mechanisms of those effects. The expression of miR-21 was quantified in serum samples from patients with NSCLC. A549 cells were transfected with miR-NC-sponge or miR-21-sponge only, or with miR-21-sponge plus PDCD4 small-interfering RNA (siRNA). The expression of miR-21 and PDCD4 mRNA in transfected cells was quantified by real-time polymerase chain reaction and the expression of PDCD4 protein by Western blot. Cell proliferation, apoptosis, migration, and invasion assays were performed to determine the biological effects of miR-21 expression and PDCD4 inhibition. miR-21 was overexpressed in serum from patients with NSCLC. Reduced miR-21 expression was observed following transfection with miR-21-sponge in A549 NSCLC cells. Co-transfection of miR-21-sponge with PDCD4 siRNA upregulated miR-21 expression in these cells. PDCD4 mRNA and protein levels were increased 2.14-fold and 2.16-fold, respectively, following inhibition of miR-21 expression. Inhibition of miR-21 expression following transfection of miR-21-sponge reduced cell proliferation, migration, and invasion of A549 cells. Depletion of PDCD4 by siRNA transfection reversed the reduction of cell proliferation, migration, and invasion induced by inhibition of miR-21 in A549 cells. It indicates that miR-21 is highly expressed in patients with NSCLC and inhibition of miR-21 expression reduces proliferation, migration, and invasion of A549 cells by upregulating PDCD4 expression. Modulation of miR-21 or PDCD4 expression may provide a potentially novel therapeutic approach for NSCLC.

Venous thromboembolism (VTE) includes thrombotic disease of venous system, but primarily includes lower extremity deep vein thrombosis (DVT) and pulmonary embolism (PE). Population-based epidemiological studies have shown an association between systemic autoimmune diseases and VTE[1]. The Padua prediction score(PPS) is a new 20-point risk assessment model proposed by Professor Barbar et al[2] in 2010. A large number of researches have shown that low serum albumin concentration is associated with an increased risk of VTE [3],but there is a lack of studies on serum albumin in VTE, and there are no reports on PPS in rheumatology inpatients. To investigate the status of VTE in patients in the department of rheumatology, and to explore the value of PPS combined with serum albumin in the identification of VTE in this patient population. Baseline data of inpatients in rheumatology department were collected at Sichuan Provincial People's Hospital from September 2018 to September 2020. Occurrence of VTE was compared between high and low risk groups. PPSs were analyzed in VTE and non-VTE patients. Multivariate logistic regression was used to analyze the independent risk factors of VTE. The receiver operating characteristic curve was used to evaluate the probablity of value of rheumatic inpatients with VTE assessed by PPS,serum albumin and PPS with serum albumin. P<0.05 indicates that the difference was statistically significant. A total of 2282 patients were included in this study, and 50(2.2%) had symptomatic VTE. Among the symptomatic VTE cases,38(1.6%) had DVT only,8(0.4%) had PE only, and 4(0.2%) were diagnosed with DVT and PE. PPSs in VTE and non-VTE groups were 3.00(2.00~6.00) and2.00(1.00~2.00) respectively (P< 0.05). One hundred and eighty-eight cases was divided into high-risk group of VTE (PPS≥4), while 2094 cases (PPS<4) were in the low-risk group. Logistic regression analysis showed that known thrombophilic condition, history of VTE, reduced mobility, and D-dimer were independent risk factors of VTE in rheumatology patients, the odd ration(OR) values were 161.90, 26.08, 8.73,and1.04. Serum albumin was the independent protection factor [OR= 0.92(95%CI:0.87~0.98)]. The AUC of PPS model, serum albumin model and the combined predictive model were 0.77, 0.75, 0.84, respectively. The difference between the combined prediction model and PPS model was statistically significant (Z=3.813, P<0.05). The optimal sensitivity of PPS and serum albumin models is 60%, 82%, respectively, and the optimal specificity of is 82.5%,58.6%, respectively. The combination model corresponds to a sensitivity of 62% and a specificity of 90.4%. The incidence of symptomatic VTE was relatively higher in hospitalized patients in rheumatology department. Serum albumin was the protective factor. The combination of albumin and PPS can improve the accuracy of screening for VTE in rheumatology in-patients. [1]Tamaki H,Khasnis A.Venous thromboembolism in systemic autoimmune diseases: A narrative review with emphasis on primary systemic vasculitides.[J].Vasc Med, 2015, 20: 369-76. [2]Barbar S, Noventa F, Rossetto V,et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score[J]. J Thromb Haemost,2010,8(11):2450–2457. [3]Kunutsor SK,Seidu S,Katechia DT et al. Inverse association between serum albumin and future risk of venous thromboembolism: interrelationship with high sensitivity C-reactive protein.[J].Ann Med, 2018, 50: 240-248. None declared

The phenomenological model for cell shape deformation and cell migration Chen (BMM 17:1429–1450, 2018), Vermolen and Gefen (BMM 12:301–323, 2012), is extended with the incorporation of cell traction forces and the evolution of cell equilibrium shapes as a result of cell differentiation. Plastic deformations of the extracellular matrix are modelled using morphoelasticity theory. The resulting partial differential differential equations are solved by the use of the finite element method. The paper treats various biological scenarios that entail cell migration and cell shape evolution. The experimental observations in Mak et al. (LC 13:340–348, 2013), where transmigration of cancer cells through narrow apertures is studied, are reproduced using a Monte Carlo framework.

Skin contraction is an important biophysical process that takes place during and after recovery of deep tissue injury. This process is mainly caused by fibroblasts (skin cells) and myofibroblasts (differentiated fibroblasts which exert larger pulling forces and produce larger amounts of collagen) that both exert pulling forces on the surrounding extracellular matrix (ECM). Modelling is done in multiple scales: agent-based modelling on the microscale and continuum-based modelling on the macroscale. In this manuscript we present some results from our study of the connection between these scales. For the one-dimensional case, we managed to rigorously establish the link between the two modelling approaches for both closed-form solutions and finite-element approximations. For the multi-dimensional case, we computationally evidence the connection between the agent-based and continuum-based modelling approaches.

Pancreatic ductal adenocarcinoma (PDAC) is a highly invasive cancer with a poor prognosis. Although microRNA (miRNA) transcripts have a crucial role in carcinogenesis and development, little information is known regarding the aberrant DNA methylation of miRNAs in PDAC. Using methylated DNA immunoprecipitation-chip analysis, we found that miR-615-5p was hypermethylated in its putative promoter region, which silenced its expression in PDAC cell lines. In addition, the overexpression of miR-615-5p in pancreatic cancer cells suppressed cell proliferation, migration and invasion. Insulin-like growth factor 2 (IGF2) is an imprinted gene, and its abnormal expression contributes to tumor growth. Here, we identified IGF2 as a target of miR-615-5p using a luciferase reporter assay. IGF2 upregulation in PDAC tissues was not correlated with a loss of imprinting but was inversely correlated with miR-615-5p downregulation. In addition, miR-615-5p suppressed pancreatic cancer cell proliferation, migration and invasion by directly targeting IGF2, and this effect could be reversed by co-transfection with IGF2. Furthermore, the stable overexpression of miR-615-5p inhibited tumor growth in vivo and was correlated with IGF2 expression. Using RNA sequencing, we further identified miR-615-5p as potentially targeting other genes, such as the proto-oncogene JUNB , and interfering with the insulin signaling pathway. Taken together, our results demonstrate that miR-615-5p was abnormally downregulated in PDAC cells due to promoter hypermethylation, which limited its inhibition of IGF2 and other target genes, thereby contributing to tumor growth, invasion and migration. These data demonstrate a novel and important role of miR-615-5p as a tumor suppressor in PDAC.

To construct a whole-of-system model to inform strategies that reduce the burden of cardiovascular disease (CVD) in Australia. A system dynamics model was developed with a multidisciplinary modelling consortium. The model population comprised Australians aged 40 years and over, and the scope encompassed acute and chronic CVD as well as primary and secondary prevention. Health outcomes were CVD-related deaths and hospitalisations, and economic outcomes were the net benefit from both the healthcare system and societal perspectives. The eight strategies broadly included creating social and physical environments supportive of a healthy lifestyle, increasing the use of preventive treatments, and improving systems response to acute CVD events. The effects of strategies were estimated as relative differences to the business-as-usual between 2019-2039. Probabilistic sensitivity analysis produced uncertainty intervals of interquartile ranges (IQR). The greatest reduction in CVD-related deaths was seen in strategies that improve systems response to acute CVD events (8.9%, IQR: 7.7-10.2%), yet they resulted in an increase in CVD-related hospitalisations due to future recurrent admissions (1.6%, IQR: 0.1-2.3%). This flow-on effect highlighted the importance of addressing underlying CVD risks. On the other hand, strategies targeting the broad environment that supports a healthy lifestyle were effective in reducing both hospitalisations (7.1%; IQR: 5.0-9.5%) and deaths (8.1% reduction; IQR: 7.1-8.9%). They also produced an economic net benefit of AU$43.3 billion (IQR: 37.7-48.7) using a societal perspective, largely driven by productivity gains. Overall, strategic planning to reduce the burden of CVD should consider the varying effects of strategies over time and beyond the health sector.