MiR-23b-3p alleviates Sjögren's syndrome by targeting SOX6 and inhibiting the NF-κB signaling.

OBJECTIVE: MicroRNA-23b-3p has been demonstrated to act as a safeguard against several autoimmune diseases. However, its role in Sjögren's syndrome (SS) remains unclear. METHODS: In order to investigate its role in SS, we administered agomiR-23b-3p or agomiR-NC to non-obese diabetic (NOD) mice via tail vein weekly for 6 weeks. The study examined the saliva flow rate, histological changes in submandibular glands, and levels of autoantibodies. Additionally, the levels of several cytokines, cell apoptosis, and NF-κB signaling were evaluated. The protective effect of miR-23b-3p was confirmed in a cell model. RESULTS: The results demonstrated that miR-23b-3p overexpression improved salivary flow rates, inhibited lymphocyte infiltration, reduced cytokine levels, and suppressed cell apoptosis in NOD mice. Moreover, NF-κB signaling was inactivated following miR-23b-3p overexpression. In a cellular model of SS, overexpression of miR-23b-3p protected submandibular gland epithelial cells exposed to IFN-γ against apoptosis and inflammation by targeting SOX6. CONCLUSIONS: The study concludes that miR-23b-3p alleviates SS by targeting SOX6 and inhibiting the NF-κB signaling pathway. The miR-23b-3p/SOX6 axis represents a promising avenue for the development of novel therapeutic strategies for SS.

Safety and learning curve analysis of robotic-assisted pancreaticoduodenectomy: experience of a single surgeon.

Although prior studies have discussed learning curves (LC) of robotic-assisted pancreaticoduodenectomy (RPD), a recognized definition is lacking. This study analyzed the clinical outcomes of 85 consecutive RPD cases performed by a single surgeon to evaluate the safety and learning curve of RPD using the da Vinci Xi robotic system. There were 51 male and 34 female patients, with a median age of 64 (20-87) years. The average preoperative body weight and BMI were 64.15 ± 11.43 kg and 23.36 ± 3.33 kg/m2, respectively. The clinical outcomes of each patient were analyzed using the textbook outcome(TO), and the learning curve of the RPD was evaluated by calculating the TO rate of patients using the cumulative sum analysis method (CUSUM).The operation time (OT) was 288.92 ± 44.41 min, and the postoperative hospital stay was 10 (1-134) days. In total, 23.52% (20/85), 5.88% (5/85), 2.35% (2/85), and 5.9% (5/85) experienced grade IIIa, IIIb, IV, and V complications. A total of 46 patients achieved TO outcomes (TO group), while 39 did not (non-TO group). The smoking rate in the TO group was lower (P < 0.05) and the albumin level was higher (P < 0.05) than that in the non-TO group. The TO rate became positive after the 56th case, all patients were divided into a learning improvement group (56 cases) and a proficient group (29 cases). The total bilirubin level in the learning improvement group was lower (P < 0.05) and the bleeding volume was higher (P < 0.05).RPD is safe and effective for carefully selected patients. The learning curve was completed after 56 patients.

Screening and Validation of Independent Predictors of Poor Survival in Pancreatic Cancer.

Pancreatic cancer is a digestive system malignant tumor with high mortality and poor prognosis, but the mechanisms of progression remain unclear in pancreatic cancer. It's necessary to identify the hub genes in pancreatic cancer and explore the novel potential predictors in the prognosis of pancreatic cancer. We downloaded two mRNA expression profiles from Gene Expression Omnibus and The Cancer Genome Atlas Pancreatic Cancer (TCGA-PAAD) datasets to screen the commonly differentially expressed genes in pancreatic cancer by limma package in R. Subsequently, measurement of the functional similarity among the 38 DEGs in common was performed to identify the hub genes using GOSemSim package. Then, survival analysis and Cox regression were applied to explore prognosis-related hub genes using the survival package. Statistics analysis by two-tailed Student's t-test or one-way based on TCGA-PAAD datasets and qPCR detection in clinical samples were performed to explore the correlations between expression of hub genes in pancreatic cancer tissues and clinical parameters. Based on integrated analysis of TCGA and GEO datasets, we screened 38 DEGs in common, which were all up-regulated. The functional similarity results showed that 10 DEGs including TSPAN1, MSLN, C1orf116, PKP3, CEACAM6, BAIAP2L1, PPL, RAB25, ERBB3, and AP1M2 in the DEGs in common, which had the higher average functional similarity, were considered as the hub genes. Survival analysis results and Cox regression analysis showed that TSPAN1, CEACAM6, as well as ERBB3 were all associated with poor overall survival of PC. qPCR results showed that the expression levels of TSPAN1 and ERBB3 were significantly upregulated in the PC tissues. The statistical analysis results revealed that TSPAN1 expression correlated significantly with histologic grade, T stage, clinical stage, and vital status by two-tailed Student's t-test or one-way ANOVA; ERBB3 expression correlated significantly with T stage, clinical stage, and vital status by two-tailed Student's t-test or one-way ANOVA. We found that TSPAN1 and ERBB3 could be independent predictors of poor survival in pancreatic cancer.

LINC00641/miR-4262/NRGN axis confines cell proliferation in glioma.

Glioma is the most prevalent brain malignancy with high mortality. In recent decades, the regulatory role of long noncoding RNAs (lncRNAs) has been unmasked in glioma. In this study, we focused on the function and mechanism of LINC00641 in glioma. First of all, we found that LINC00641 was expressed at a low level in glioma cell lines. Importantly, overexpression of LINC00641 prevented cell proliferation but enhanced cell apoptosis. Meanwhile, NRGN, a previously-reported downregulated mRNA in GBM, was disclosed as a tumor suppressor in glioma cells. Besides, we verified that NRGN could be positively regulated by LINC00641 in glioma cells. Moreover, the cellular distribution of LINC00641 was identified to be cytoplasmic. Therefore, bioinformatics analysis and mechanism experiments were carried out and we determined that miR-4262 was the shared miRNA between LINC00641 and NRGN. In contrast to LINC00641 and NRGN, miR-4262 was dramatically upregulated in glioma cells. Furthermore, we confirmed that LINC00641 acted as a ceRNA in glioma cells via absorbing miR-4262 to upregulate NRGN. More importantly, silenced NRGN countervailed the repression on glioma cell proliferation caused by LINC00641 upregulation. Collectively, our findings unveiled that LINC00641 serves as a tumor inhibitor in glioma by targeting miR-4262/NRGN axis, providing a new potential therapeutic target for glioma patients.

Morin Protects LPS-Induced Mastitis via Inhibiting NLRP3 Inflammasome and NF-κB Signaling Pathways.

Mastitis is one of the most common diseases that both affects human and animals. Morin is derived from the member of Moraceae family, which has been used in the treatment of many inflammatory diseases. The purpose of this study was to test the protective effect of morin on LPS-induced mastitis and to clarify the possible mechanism. In vivo, the mastitis model was established by lipopolysaccharide (LPS), and morin was treated 1 h before stimulation of LPS. In vitro, peritoneal macrophages were used to test the regulation mechanisms of morin on mastitis. The inflammatory cytokines (TNF-α, IL-1ß, and IL-6) was tested by ELISA. Myeloperoxidase (MPO) activity was measured by MPO kit. The expression of NLRP3 inflammasome and NF-κB signaling pathway proteins were detected by western blotting. The results showed that morin alleviated the pathological damage of mammary gland tissues, MPO activity, and the production of TNF-α, IL-1ß, and IL-6 in mammary gland tissues. In vitro, morin significantly suppressed the production of inflammatory cytokines. In addition, it also inhibited the activation of NLRP3 inflammasome and NF-κB signaling pathway induced by LPS. In conclusion, the present study suggested that the protective effect of morin against LPS-induced mastitis may be due to its ability to inhibit NLRP3 inflammasome expression and NF-κB signaling pathway.

LncRNA PCED1B-AS1 activates the proliferation and restricts the apoptosis of glioma through cooperating with miR-194-5p/PCED1B axis.

Glioma with poor prognosis is accepted as a lethal, malignant intracranial tumor among central nervous system diseases. It has been frequently exhibited that long noncoding RNAs (lncRNAs) exert indispensable functions in glioma through regulating gene expression through various molecular mechanisms. To unveil a novel lncRNA functioning in glioma, we browsed the cancer genome atlas dataset and chose the lncRNA PC-esterase domain containing 1B antisense RNA 1 (PCED1B-AS1) for further investigations. Loss-of-function experiments depicted that the proliferation ability was restrained and apoptosis ability was induced in glioma cells by PCED1B-AS1 silencing and this phenomenon was also observed when PCED1B was knocked down. In view of the position of PCED1B-AS1 in the cytoplasm, we produced the Venn diagram and discovered one shared microRNA of PCED1B-AS1 and PCED1B. The competing endogenous RNA network formed by PCED1B-AS1, miR-194-5p, and PCED1B was attested by mechanism assays. Rescue experiments reconfirmed that miR-194-5p suppression or PCED1B overexpression neutralized the obstructive impacts of PCED1B-AS1 silence on proliferation and the promoting effects of PCED1B-AS1 silence on apoptosis. The modulation mechanism of the PCED1B-AS1/miR-194-5p/PCED1B axis in glioma was investigated and affirmed, which supports researchers with a new insight into the therapy of patients with glioma.

Efficacy comparison of radiofrequency ablation and hepatic resection for hepatocellular carcinoma: A meta-analysis.

OBJECTIVES: The objective of this study is to compare the therapeutic efficacy of radiofrequency ablation (RFA) and hepatic resection (HR) for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A literature search was performed for comparative studies reporting outcomes of both RFA and HR for HCC. Pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. RESULTS: A total of 4812 patients with HCC were included, with 2419 in the RFA group and 2393 in the HR group. The 3- and 5-year overall survival rates in the HR group were significantly higher than those in the RFA group (OR: 0.68, 95% CI: 0.58-0.79, P < 0.00001; OR: 0.57, 95% CI: 0.50-0.65, P < 0.00001, respectively). 1-, 3-, 5-year disease-free survival and correspond recurrence-free survival rates were all better in HR group. CONCLUSION: RFA gets promising clinical outcomes for HCC treatments but is not yet comparable to surgery. HR is still the first-line treatment for HCC.

Effect of Cdc42 gene inhibited on proliferation, migration and invasion in human hepatocellular carcinoma cells / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of Cdc42-shRNA plasmid to proliferation, migration, invasion and other malignant biological behavior in hepatoma SMMC-7721 cells.</p><p><b>METHODS</b>Cdc42-shRNA interfering vector transfected to SMMC-7721 cells with liposome method. The growth curve of transfected cells SMMC-7721, U6-control, Cdc42-shRNA2 was detected by MTT. The cells mobility was detected by wound healing experiment. Transwell chamber experiments to observe the cell migration and invasion. Detected AFP and PCNA expression level by Western blot.Human hepatoma SMMC-7721 transplanted subcutaneously in nude mouse, detected the expression of Cdc42 of the tumor by immunohistochemistry.t test was used to analyze the data between two groups.</p><p><b>RESULTS</b>The doubling time of Cdc42-shRNA2, U6-control and SMMC7721 was 42.7 h, 34.9 h and 35.1 h. The relative migration distance of Cdc42-shRNA2 and U6-control on 36 h was (47.1 ± 4.1)% and (86.6 ± 5.3)% (t=-10.21, P<0.05). Transwell chamber experimental methods showed the numbers of permeating cells were 18.2 ± 2.1(Cdc42-shRNA2) and 41.0 ± 3.5 (U6-control) (t=-9.67, P<0.05) on 24 h. The AFP and PCNA expression of hepatoma cells is significantly inhibited after the Cdc42-shRNA2 was transfected compared with U6-control group.The tumor average weight of group Cdc42-shRNA2 was (335.1 ± 178.2) mg, which was much lighter than that of SMMC-7721 group ((925.3 ± 241.4) mg) and U6-control group ((910.5 ± 225.6) mg) (t=-4.47, -4.39; P<0.05) and the Cdc42 expression was also weak positive.</p><p><b>CONCLUSION</b>Cdc42 interfere with plasmid significant changes in human malignant biological behavior of hepatocellular carcinoma cells, and reduces liver cancer cell growth, invasion and metastasis of capacity.</p>