LncRNA SNHG8 regulates the migration and angiogenesis of pHUVECs induced by high glucose via the TRPM7/ERK1/2 signaling axis.

This study aimed to evaluate the regulatory effect and molecular mechanism of long noncoding RNA small nucleolus RNA host gene 8 (LncRNA SNHG8) in the migration and angiogenesis of primary human umbilical vein endothelial cells (pHUVECs) under high-glucose (HG) conditions. The HG-induced endothelial injury model was established in vitro.The cell model of silencing SNHG8, overexpressing SNHG8, and silencing TRPM7 was established by transfecting SNHG8-siRNA, SNHG8 plasmid and TRPM7-siRNA into cells with liposomes.The SNHG8 level was determined through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression levels of transient receptor potential melastatin 7 (TRPM7), endothelial nitric oxide synthase (eNOS), p-eNOS, extracellular signal-regulated kinase 1/2(ERK1/2), and p-ERK1/2 were assessed through western blot. Nitric oxide (NO) levels were measured with DAF-FM. pHUVEC migration was examined through wound healing and Transwell assay, and pHUVEC angiogenesis was observed through a tube formation assay. Results showed that HG promoted the expression of lncRNA SNHG8 and TRPM7 and decreased the ratio of p-eNOS/eNOS and p-ERK1/2/ERK1/2 in pHUVECs . NO production, migration , and angiogenesis were inhibited in pHUVECs under HG conditions. Silencing lncRNA SNHG8 and TRPM7 could significantly reverse the HG-induced decrease in eNOS activation, NO production , migration, and angiogenesis . SNHG8 and U0126 (ERK pathway inhibitor) overexpression enhanced the HG effects, whereas using U0126 did not affect the TRPM7 expression. In conclusion, lncRNA SNHG8 participates in HG-induced endothelial cell injury and likely regulates NO production, migration, and angiogenesis of pHUVECs via the TRPM7/ERK1/2 signaling axis.

Impact of PIWIL1 Single Nucleotide Polymorphisms on Gastric Cancer Risk in a Chinese Population.

Background: PIWI-like proteins contribute to the onset and progression of carcinogenesis. Whether single nucleotide polymorphisms (SNPs) in the PIWI-like 1 (PIWIL1) gene affect the morbidity and mortality of gastric cancer (GC) remains unclear. To investigate the efficacy of PIWIL1 SNPs genotype on the morbidity and mortality of GC and its interaction within PIWIL1 gene SNPs variation and between elevated plasma glucose. Materials and Methods: We conducted a case-control study that contained 216 GC patients and 204 cancer-free controls to compare differential expression of PIWIL1 SNPs. Results: PIWIL1 gene rs1106042 AA and AG genotypes were associated with significantly reduced GC risk (odds ratio [OR]: 0.15 and 0.26, p < 0.001 and p = 0.016), and rs10773771 CT+CC type significantly increased cancer risk (OR: 1.54 p = 0.037). We observed strong associations between rs10773771 and pathological type (p = 0.012), rs11703684, and invasion depth (p = 0.012). We noticed significant gene-gene interaction between rs1106042 and rs10773771 (p = 0.0107). Interaction between the copresence of rs1106042 GG plus hyperglycemia was also significant (relative excess risk due to interaction: 28.78, attributable proportion due to interaction: 68.2%, synergy index: 3.32). Patients with rs1892723 TT and rs1892722 GG+GA type had better survival (p = 0.030 and p = 0.048). Conclusion: rs10773771 CT+CC was associated with GC risk increase, rs1106042 AA and AG function as a protective factor. rs1892723 CT+TT and rs1892722 AA type may portend a poor prognosis. Elevated fasting plasma glucose will significantly increase the risk of PIWIL gene rs1106042 GG carcinogenesis by multiplicative interaction.

Prognostic value of long-term antidiabetic and antihypertensive therapy in postoperative gastric cancer patients: the FIESTA study.

BACKGROUND: Gastric cancer is often comorbid with hypertension and diabetes mellitus and increases the mortality risk. MATERIALS AND METHODS: We conducted this prospective cohort study to investigate antidiabetics and antihypertensives' impact on gastric cancer survival. 3012 patients with gastric carcinoma undergoing radical gastrectomy were enrolled since January 2000 and followed up until July 2020. RESULTS: Hypertension and diabetes patients had worse survival than patients without hypertension and diabetes [median survival time (MST): 48 versus 112.5 months, p < 0.001 for hypertension, MST: 32.7 versus 183+ months, p < 0.001 for diabetes]. Compared to untreated patients, treated patients had better survival (MST: 109.7 months versus 39.1 months, p < 0.001 for antihypertensives, MST: 120.9 months versus 22.3 months, p < 0.001 for antidiabetics). Antihypertensives and antidiabetics were related to 42% (HR 0.58, 95% CI 0.47-0.73, p < 0.001) and 70% (HR 0.30, 95% CI 0.24-0.38, p < 0.001) reduced mortality risk relative to those without medications. metformin and Calcium channel blockers can better-improved prognosis compared to others (p = 0.00029 and p = 0.015). CONCLUSION: Post-surgical gastric cancer patients could benefit substantially from anti-diabetes and antihypertensive therapy. Metformin and Calcium channel blockers may be superior to other medications.

Hyperglycemia induces gastric carcinoma proliferation and migration via the Pin1/BRD4 pathway.

Diabetes is a potential risk factor for gastric cancer (GC). Pin1, a peptidyl-prolyl cis/trans isomerase, promotes GC cell proliferation and migration. The role and underlying mechanism of the Pin1/BRD4 axis in hyperglycemia-induced proliferation and migration of GC cells were analyzed in vivo and in vitro. Proliferation and migration of GC cells were measured; Pin1 and BRD4 expression of the cell cycle were determined. Pin1 and BRD4 were downregulated by transfecting Pin1 shRNA lentivirus into GC cells and JQ1-intervention GC cells. Tumor formation and lung metastasis were assessed in vivo. Inhibition of Pin1 and BRD4 significantly suppressed high-glucose (HG)-induced GC cell proliferation and migration. HG enhanced G1/S cell-cycle transition, associated with increased Pin1 and BRD4 expression. Silencing Pin1 significantly downregulated the expression of BRD4 and NAP1L1 and upregulated that of P21 in GC cells. In vivo studies indicated that hyperglycemia promotes tumor growth and lung metastasis by inducing Pin1 and BRD4 expression. Thus, Pin1/BRD4 plays an important role in hyperglycemia-promoted tumor growth. The significance of these findings toward improved prognosis of diabetic patients with GC cannot be underestimated.

The Impact of Bariatric Surgery Versus Non-Surgical Treatment on Blood Pressure: Systematic Review and Meta-Analysis.

The purpose of this study was to compare bariatric surgery versus non-surgical treatment on blood pressure for patients with obesity. Nineteen RCTs (1353 total patients) were included. In the pooled analyses, bariatric surgery reduces more systolic blood pressure (WMD: - 3.937 mmHg, CI95%: - 6.000 to - 1.875, p < 0.001, I2 = 0%), diastolic blood pressure (WMD: - 2.690 mmHg, CI95%: - 3.994 to - 1.385, P < 0.001, I2 = 0%) and more antihypertensives. In subgroup analyses, patients after Roux-en-Y gastric bypass, with poor control of hypertension (BP > 130/80 mmHg) and diabetes mellitus (HbA1C > 7.0%, FPG > 7.0 mmol/L), elder patients (> 45 years), non-severe obesity (BMI < 40 kg/cm2, body weight < 120 kg), less waist circumference (< 115 cm) tend to decrease more blood pressure. Besides, patients after surgery also lost more weight (p < 0.001), decreased more waist circumference (p < 0.001), fasting plasma glucose (p < 0.001), glycosylated hemoglobin (p < 0.001), triglycerides (p < 0.001), hsCRP (p = 0.001), increased more high-density lipoprotein cholesterol (p < 0.001), and had better remission of metabolic syndrome (p < 0.001). Changes in total cholesterol, low-density lipoprotein cholesterol, renal function, resting heart rate, and 6-min walking test were not significantly different. Therefore, bariatric surgery is more effective than non-surgical treatment in controlling patients' blood pressure.