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Background Emerging evidence has shown that dysregulation function of long non-coding RNAs (lncRNAs) implicated in gastric cancer (GC). However, the role of the differentially expressed lncRNAs in GC has not fully explained. Methods LncRNA expression profiles were determined by lncRNA microarray in five pairs of normal and GC tissues, further validated in another 75 paired tissues by quantitative real-time PCR (qRT-PCR). Overexpression of lncRNA MT1JP was conducted to assess the effect of MT1JP in vitro and in vivo. The biological functions were demonstrated by luciferase reporter assay, western blotting and rescue experiments. Results LncRNA MT1JP was significantly lower in GC tissues than adjacent normal tissues, and higher MT1JP was remarkably related to lymph node metastasis and advance stage. Besides, GC patients with higher MT1JP expression had a well survival. Functionally, overexpression of lncRNA MT1JP inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro, and inhibited tumor growth and metastasis in vivo. Functional analysis showed that lncRNA MT1JP regulated FBXW7 expression by competitively binding to miR-92a-3p. MiR-92a-3p and down-regulated FBXW7 reversed cell phenotypes caused by lncRNA MT1JP by rescue analysis. Conclusion MT1JP , a down-regulated lncRNA in GC, was associated with malignant tumor phenotypes and survival of GC. MT1JP regulated the progression of GC by functioning as a competing endogenous RNA (ceRNA) to competitively bind to miR-92a-3p and regulate FBXW7 expression. Our study provided new insight into the post-transcriptional regulation mechanism of lncRNA MT1JP , and suggested that MT1JP may act as a potential therapeutic target and prognosis biomarker for GC.

In consideration of the technical requirements for compact and efficient heat-exchange equipment in industrial fields, such as sludge incineration heat utilization, solar thermal power generation and aerospace, this paper analysed the supercritical nitrogen flow and heat transfer processes in square straight micro-fin tube, triangle straight micro-fin tube and smooth circular tube under different Re numbers, and obtained the changes in velocity field, local turbulence intensity, average Nusselt number and resistance coefficient of supercritical fluid in micro-fin tubes. Moreover, it was found that the introduction of micro fin was able to improve the turbulent heat transfer performance of supercritical fluid in tubes within certain Re number range.

BackgroundPatients with inflammatory bowel disease (IBD) are at increased risk of gastrointestinal and extraintestinal malignancies. However, the associations between IBD and prostate cancer (PCa) risk remain conflicting.MethodsWe conducted a systematic literature search in PubMed, EMBASE, and Web of Science databases. According to the inclusion and exclusion criteria, a total of nine studies were included in the meta-analysis. The pooled standardized incidence ratios (SIRs) or relative risks (RRs) and corresponding 95% confidence intervals (CIs) were calculated to determine the relationship of IBD and PCa risk.ResultsFor cohort studies, the pooled SIR was 1.33 (95% CI = 1.03–1.71). The further subgroup analysis showed that the PCa risk was higher in patients with ulcerative colitis (UC) (pooled SIR = 1.58, 95% CI = 1.08–2.30), but not in patients with Crohn’s disease (CD) (pooled SIR = 1.12, 95% CI = 0.97–1.31). Besides, for the three case-control studies, the results indicated that compared with normal group, the pooled RR of PCa was 1.81 for the patients with IBD (95% CI = 1.43–2.29). In addition, sensitivity analysis indicated that the results were robust and no significant publication bias were observed.ConclusionsOur findings based on the large and multicenter samples strongly indicated that men with IBD especial UC have significantly elevated PCa risk. Future efforts are needed to define the mechanism underlying the link between IBD and PCa or clinically significant PCa risk.

The functions of the influenza virus neuraminidase has been well documented but those of the mammalian neuraminidases remain less explored. Here, we characterize the role of neuraminidase 1 (NEU1) in unilateral ureteral obstruction (UUO) and folic acid (FA)-induced renal fibrosis mouse models. We find that NEU1 is significantly upregulated in the fibrotic kidneys of patients and mice. Functionally, tubular epithelial cell-specific NEU1 knockout inhibits epithelial-to-mesenchymal transition, inflammatory cytokines production, and collagen deposition in mice. Conversely, NEU1 overexpression exacerbates progressive renal fibrosis. Mechanistically, NEU1 interacts with TGFβ type I receptor ALK5 at the 160-200aa region and stabilizes ALK5 leading to SMAD2/3 activation. Salvianolic acid B, a component of Salvia miltiorrhiza , is found to strongly bind to NEU1 and effectively protect mice from renal fibrosis in a NEU1-dependent manner. Collectively, this study characterizes a promotor role for NEU1 in renal fibrosis and suggests a potential avenue of targeting NEU1 to treat kidney diseases. The influenza virus neuraminidase has been well documented, yet the functions of mammalian neuraminidases remain less explored. Here, the authors show that neuraminidase 1 promotes renal fibrosis development by interacting with ALK5 to activate SMAD2/3.

This study aimed to comprehensively evaluate the effect of PBL on problem-solving, self-directed learning, and critical thinking ability of pharmaceutical students through a randomized controlled trial (RCT) and meta-analysis of RCTs. In 2021, 57 third-year pharmacy students from China Pharmaceutical University were randomly divided into a PBL group and a lecture-based learning (LBL) group. Mean scores were compared between the two groups for problem-solving, self-directed learning, communication skills, critical thinking, and final exam grades. Students' feedback on the implementation of PBL was also collected. A meta-analysis was subsequently performed. Two authors independently conducted a comprehensive search of two databases (PubMed and CNKI). Eligible studies with effective data were included and the valuable data were extracted for analysis. Quality of involved studies was assessed by the Cochrane Collaboration's tool. All analyses of statistics were conducted using the 'metafor' package in R software. The PBL group had significantly higher mean scores for problem-solving (8.43±1.56) and self-directed learning (7.39±1.19) than the LBL group (7.02±1.72 and 6.41±1.28, respectively). The PBL group also showed better communication skills (8.86±1.47) than the LBL group (7.68±1.89). The mean level of critical thinking was significantly higher in the PBL group than the LBL group (p = 0.02). The PBL group also had better final exam grades (79.86±1.38) compared to the LBL group (68.1±1.76). Student feedback on PBL implementation was positive. The outcome of subsequent meta-analysis including 8 eligible studies involved 1819 participants showed that the use of PBL significantly improved problem-solving ability (SMD = 1.12, 95% CI = 0.25-1.99) and PBL was also associated with better performance in self-directed learning (SMD = 1.55, 95% CI = 0.64-2.45). However, there was no significant difference in the final exam score in the PBL group compared to the LBL control group (SMD = 0.23, 95% CI = -0.08-0.53). This study found that PBL is an effective teaching method for pharmacy students.

Glucagon promotes hepatic gluconeogenesis and maintains whole-body glucose levels during fasting. The regulatory factors that are involved in fasting glucagon response are not well understood. Here we report a role of p52, a key activator of the noncanonical nuclear factor-kappaB signaling, in hepatic glucagon response. We show that p52 is activated in livers of HFD-fed and glucagon-challenged mice. Knockdown of p52 lowers glucagon-stimulated hyperglycemia, while p52 overexpression augments glucagon response. Mechanistically, p52 binds to phosphodiesterase 4B promoter to inhibit its transcription and promotes cAMP accumulation, thus augmenting the glucagon response through cAMP/PKA signaling. The anti-diabetic drug metformin and ginsenoside Rb1 lower blood glucose at least in part by inhibiting p52 activation. Our findings reveal that p52 mediates glucagon-triggered hepatic gluconeogenesis and suggests that pharmacological intervention to prevent p52 processing is a potential therapeutic strategy for diabetes. Elevated glucagon level in obesity and diabetes promotes hepatic glucose production and hyperglycemia. Here the authors report that NF-κB2 augments the hepatic glucagon responses by inhibiting PDE4B induction, and that metformin lowers blood glucose in part by inhibiting NF-κB2.

Within tumor microenvironment, the presence of preexisting antitumor CD8+ T Q7 cells have been shown to be associated with a favorable prognosis in most solid cancers. However, in the case of prostate cancer (PCa), they have been linked to a negative impact on prognosis. To gain a deeper understanding of the contribution of infiltrating CD8+ T cells to poor prognosis in PCa, the infiltration levelsof CD8+ T cells were estimated using the TCGA PRAD (The Cancer Genome Atlas Prostate Adenocarcinoma dataset) and MSKCC (Memorial Sloan Kettering Cancer Center) cohorts. Bioinformatic analyses revealed that CD8+ T cells likely influence PCa prognosis through increased expression of immune checkpoint molecules and enhanced recruitment of regulatory T cells. The MLXIPL was identified as the gene expressed in response to CD8+ T cell infiltration and was found to be associated with PCa prognosis. The prognostic role of MLXIPL was examined in two cohorts: TCGA PRAD (p = 2.3E-02) and the MSKCC cohort (p = 1.6E-02). Subsequently, MLXIPL was confirmed to be associated with an unfavorable prognosis in PCa, as evidenced by an independent cohort study (hazard ratio [HR] = 2.57, 95% CI: 1.42- 4.65, p = 1.76E-03). In summary, the findings suggested that MLXIPL related to tumor-infiltrating CD8+ T cells facilitated a poor prognosis in PCa.

Background Health-related quality of life (HRQoL) has been brought up for decades in haemophilia patients. However, no data to date are available about HRQoL in children with haemophilia using long-term follow up data. This nearly 4-year follow-up study aimed to assess the long-term HRQoL of haemophilia children. Methods A prospective cohort study among 42 children with haemophilia and their parents was conducted in August 2014 in a children’s hospital; follow-up was completed in January 2018. Primary endpoint was the change in patient HRQoL evaluated by Canadian Haemophilia Outcomes–Kids’ Life Assessment Tool (CHO-KLAT) from baseline to year 4; secondary endpoint was the impact of bleeding rates, physical activity restriction, financial burden and treatment (prophylaxis vs on-demand treatment) on HRQoL, as well as the impact of treatment on event-free survival. Results Totally 42 patients (mean age, 5.48[SD, 4.63] years) and 42 parents were included. 38 families completed 4-year follow up. Patients reported a small increase in HRQoL from baseline to year 4. The mean scores of child self-report and parent proxy report of CHO-KLAT at baseline were 60.69 (SD = 20.28) and 61.01 (SD = 12.14), respectively. Scores at follow-up were 64.69 (SD = 13.71) and 65.33 (SD = 15.78), respectively. Haemophilia patients without physical activity restriction, living in urban areas, and receiving prophylactic treatment and home injection, had higher average values for HRQoL scores than the others. Bleeding rates were proportionally negatively correlated with HRQoL. Patients who had received prophylactic treatment had better event-free survival. Conclusions Haemophilia decreased HRQoL of patients, but this effect weakened after 4 years. HRQoL of children is influenced by severity of haemophilia, bleeding rates, physical activity restriction, financial burden and treatment. Prophylactic treatment is a key factor contributing to event-free survivor prognosis and the optimal form of therapy for childhood haemophilia.

Background Brain tumors cause significant morbidity and mortality due to rapid progression and high recurrence risks. Reliable biomarkers to improve diagnosis thereof are desirable. Objective This work aimed to identify panels of biomarkers for diagnostic purposes using cerebrospinal fluid (CSF)-based metabolomics. Methods A cohort of 163 histologically-proven patients with brain disorders was involved. Comprehensive CSF-based metabolomics was achieved by liquid chromatography-quadrupole time-of-flight spectrometric (LC-Q/TOF–MS) and multivariate statistical analyses. The diagnostic performance of the metabolic markers was evaluated using receiver operating characteristic curves. Results A total of 508 ion features were detected by the LC-Q/TOF–MS analysis, of which 27 metabolites were selected as diagnostic markers to discriminate different brain tumor types. The area under the curve (AUC) was 0.91 for lung adenocarcinoma patients with brain metastases (MBT) vs. lung adenocarcinoma patients without brain metastases (NMBT), 0.83 for primary central nervous system lymphoma (PCNSL) vs. secondary central nervous system involvement of systemic lymphoma (SCNSL), 0.77 for PCNSL vs. MBT, 0.87 for SCNSL vs. MBT, 0.86 for MBT vs. nontumorous brain diseases (NT), and 0.80 for PCNSL vs. NT. Perturbed metabolic pathways between the comparisons related mainly to amino acids and citrate metabolism. Conclusions CSF-based metabolomics to a large extent reliably identifies significant metabolic differences between different brain tumors and shows great potential for diagnosis of brain tumors.

Recently N6-Methyladenosine (m6A) has been identified to guide the interaction of RNA-binding protein hnRNP C and their target RNAs, which is termed as m6A-switches. We systematically investigated the association between genetic variants in m6A-switches and bladder cancer risk. A two-stage case–control study was performed to systematically calculate the association of single nucleotide polymorphisms (SNPs) in 2798 m6A-switches with bladder cancer risk in 3,997 subjects. A logistic regression model was used to assess the effects of SNPs on bladder cancer risk. A series of experiments were adopted to explore the role of genetic variants of m6A-switches. We identified that rs5746136 (G > A) of SOD2 in m6A-switches was significantly associated with the reduced risk of bladder cancer (additive model in discovery stage: OR = 0.80, 95% CI 0.69–0.93, P = 3.6 × 10−3; validation stage: adjusted OR = 0.88, 95% CI 0.79–0.99, P = 3.0 × 10−2; combined analysis: adjusted OR = 0.85, 95% CI 0.78–0.93, P = 4.0 × 10−4). The mRNA level of SOD2 was remarkably lower in bladder cancer tissues than the paired adjacent samples. SNP rs5746136 may affect m6A modification and regulate SOD2 expression by guiding the binding of hnRNP C to SOD2, which played a critical tumor suppressor role in bladder cancer cells by promoting cell apoptosis and inhibiting proliferation, migration and invasion. In conclusion, our findings suggest the important role of genetic variants in m6A modification. SOD2 polymorphisms may influence the expression of SOD2 via an m6A-hnRNP C-dependent mechanism and be promising predictors of bladder cancer risk.