MT1G Regulates c-MYC/P53 Signal to Inhibit Proliferation, Invasion and Migration and Promote Apoptosis in Colon Cancer Cells.

INTRODUCTION: Colon cancer is a common and malignant cancer featuring high morbidity and poor prognosis. AIMS: This study was performed to explore the regulatory role of MT1G in colon cancer as well as its unconcealed molecular mechanism. METHODS: The expressions of MT1G, c-MYC, and p53 were assessed with the application of RT-qPCR and western blot. The impacts of MT1G overexpression on the proliferative ability of HCT116 and LoVo cells were measured by CCK-8 and BrdU incorporation assays. Additionally, transwell wound healing, and flow cytometry assays were employed to evaluate the invasive and migrative capacities as well as the apoptosis level of HCT116 and LoVo cells. Moreover, the activity of the P53 promoter region was assessed with the help of a luciferase reporter assay. RESULTS: It was found that the expressions of MT1G at both mRNA and protein levels were greatly decreased in human colon cancer cell lines, particularly in HCT116 and LoVo cell lines. After transfection, it was discovered that the MT1G overexpression suppressed the proliferation, migration and invasion but promoted the apoptosis of HCT116 and LoVo cells, which were then partially reversed after overexpressing c-MYC. Additionally, MT1G overexpression reduced c-MYC expression but enhanced the p53 expression, revealing that the MT1G overexpression could regulate c-MYC/P53 signal. Elsewhere, it was also shown that c-MYC overexpression suppressed the regulatory effects of MT1G on P53. CONCLUSION: To conclude, MT1G was verified to regulate c-MYC/P53 signal to repress the proliferation, migration and invasion but promote the apoptosis of colon cancer cells, which might offer a novel targeted-therapy for the improvement of colon cancer.

Baseline and early changes in circulating Serum Amyloid A (SAA) predict survival outcomes in advanced non-small cell lung cancer patients treated with Anti-PD-1/PD-L1 monotherapy.

BACKGROUND: Systemic inflammation plays an important role in carcinogenesis and is associated with overall survival in patients with different cancer types, including those treated with immune checkpoint blockade (ICB). Serum Amyloid A (SAA) is an acute-phase protein and a marker of persistent inflammation. We hypothesized that circulating SAA may predict outcomes in advanced non-small cell lung (aNSCLC) patients treated with PD-1/PD-L1 ICB. MATERIALS AND METHODS: This retrospective study included 91 aNSCLC patients who received anti-PD-(L)1 monotherapy in Sun Yat-sen University Cancer Center (Guangzhou, China) between August 2016 and June 2018. We examined the impact of circulating SAA at baseline and 8 (±2) weeks later on overall survival (OS). X-tile program was used to determine the cut-off values which optimized the significance of the split between Kaplan-Meier survival curves. Kaplan-Meier methodology and Cox regression analyses were conducted for survival analyses. RESULTS: The optimal cut-off value of baseline SAA for OS stratification was 137.6 mg/L. In univariate analysis, both high level of baseline SAA (hazard ratio [HR], 2.76; 95% confidence interval [CI], 1.47-5.18; P = 0.002) and lack of early SAA descent (HR, 1.51; 95% CI, 1.11-2.06; P = 0.009) were significantly associated with inferior OS. In multivariate analysis, gender, smoking status, performance status, liver metastasis, neutrophil-to-lymphocyte ratio, baseline SAA and early changes in SAA independently predicted OS (all with P < 0.05). A combined baseline SAA ≥ 137.6 mg/L and without early SAA descent identified a small cohort with remarkably worse OS (median, 3.2 months). CONCLUSIONS: Both high baseline and lack of early decline in circulating SAA are significantly associated with inferior outcomes in aNSCLC patients treated with PD-1/PD-L1 ICB. Combined these two SAA indexes provided improved risk stratification. The prognostic value of this simple, readily-available, and cost-effective biomarker warrants larger, prospective validation before definitive recommendation can be made.

Habitual consumption of alcohol with meals and lung cancer: a Mendelian randomization study.

BACKGROUND: The objective of this study was to determine the causal relationship between habitual alcohol consumption with meals and lung cancer. METHODS: Public genetic summary data from two large consortia [the Neale Lab and the International Lung Cancer Consortium (ILCCO)] were used for analysis. As the instrumental variables of habitual alcohol consumption with meals, data on genetic variants were retrieved from Neale Lab. Additionally, genetic data from other consortia [Global Lipid Genetics Consortium (GLGC), Tobacco, Alcohol and Genetics (TAG), Genetic Investigation of Anthropocentric Traits (GIANT)] were utilized to determine whether alcohol could causally alter some general risk factors for lung cancer. The primary outcome was the risk of lung cancer (11,348 cases and 15,861 controls in the ILCCO). The R package TwoSampleMR was used for analysis. RESULTS: Based on the inverse variance weighted method, the results of the two-sample Mendelian randomization (MR) analyses indicated that commonly consuming alcohol with meals was a protective factor, reducing lung cancer risk [odds ratio (OR) 0.175, 95% confidence interval (CI): 0.045-0.682, P=0.012]. The heterogeneity analysis revealed that the causal relationship analyses of different types of lung cancer all had low heterogeneity (P>0.05). The horizontal pleiotropic study showed that major bias was unlikely. The MR assumptions did not seem to be violated. The causal relationship analyses between habitual alcohol consumption with meals and some risk factors for cancers showed that this alcohol consumption habit was a beneficial factor for reducing body mass index (BMI) and the number of cigarettes smoked per day. CONCLUSIONS: Habitual appropriate alcohol consumption with meals is a protective factor for the development of lung cancer.

Inhibition of TNF-α sepsis of lipopolysaccharide induction using nano cerium oxide system.

Nowadays sepsis was one of the major threatening issues all over the globe which majorly causes death in high rate. To treat sepsis only few reports have been proposed with the help of anti-oxidants. This manuscript stated that the grape is rich in anti-oxidant, with the help of anti-oxidant rich grape extract Cerium oxide nanoparticles (CeO2 NPs) were synthesized eco-friendly. Further the synthesized CeO2 NPs subjected for various characterization studies which resulted in 37nm of size with agglomerated spherical shape particles. Further synthesized CeO2 NPs were subjected in vivo through tail nerves of rats to treat sepsis. CeO2 NPs stops the release TNF-α and tends to increase the ceria level in liver. Histopathological studies were performed and also reported. The obtained results were statistically significant with ANOVA LSD-Tukey's test were studied and reported in this manuscript.

Impact of Serum Apolipoprotein A-I on Prognosis and Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer: a Propensity Score-Matched Analysis.

PURPOSE: We aimed to investigate the role of apolipoprotein A-I (ApoA-I) as a predictor of prognosis and treatment efficacy of bevacizumab in patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy with or without bevacizumab. METHODS: We conducted a retrospective study on consecutive patients who were diagnosed with mCRC at Sun Yat-sen University Cancer Center. According to their pretreatment ApoA-I level, patients were divided into low- and high-ApoA-I groups. Propensity score-matched method was performed to balance baseline characteristics between two groups. Based on whether they accepted bevacizumab as a first-line therapy, patients were further divided into the chemo + bevacizumab group and the chemo group. Overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier method, log-rank test, and Cox regression. RESULTS: The optimal cutoff value for the ApoA-I level was determined to be 1.105 g/l. In the propensity-matched cohort of 508 patients, low ApoA-I was significantly associated with inferior OS (P<.001) and PFS (P<.001) than high ApoA-I. Multivariate analysis showed that ApoA-I level was an independent prognostic maker of OS (P<.001) and PFS (P=.001). PFS (P<.001) in either the high- or low-ApoA-I groups could be extended significantly after the administration of bevacizumab, and patients with a high ApoA-I level also had a better OS in the chemo + bevacizumab group than the chemo group (P=.049). CONCLUSIONS: Patients with a low ApoA-I level have poor prognoses, and they did not display an OS benefit from bevacizumab.

Effect of short message service on infant feeding practice: findings from a community-based study in Shanghai, China.

IMPORTANCE: Appropriate infant feeding practices have the potential for long-term health effects. However, research findings on improving early infant feeding practices are limited. The wide use of mobile phone short message service (SMS) provides new opportunities for health promotion and services. OBJECTIVE: To assess the effect of an SMS intervention on infant feeding practices. DESIGN AND SETTING: Quasiexperimental design with follow-up measures scheduled at 4, 6, and 12 months at 4 community health centers in Shanghai, China. Two community health centers represented the intervention group, and 2 other community health centers represented the control group. PARTICIPANTS: In total, 582 expectant mothers were recruited during the first trimester. Expectant mothers were eligible to participate if they owned a mobile phone, were first-time mothers, conceived a singleton fetus, were older than 20 years and less than 13 weeks' gestation, had completed at least a compulsory junior high school education, and had no illness that limited breastfeeding after childbirth. INTERVENTION: Mothers in the intervention group received weekly SMS messages about infant feeding from the third trimester to 12 months' post partum. MAIN OUTCOMES AND MEASURES: The primary outcome was the duration of exclusive breastfeeding (EBF). Survival analysis was used to compare the duration of EBF between the intervention group and the control group. RESULTS: Compared with the control group, the intervention group had a significantly longer median duration of EBF at 6 months (11.41 [95% CI, 10.25-12.57] vs 8.87 [95% CI, 7.84-9.89] weeks). The hazard ratio for stopping EBF in the intervention group was 0.80 (95% CI, 0.66-0.97). The intervention resulted in a significantly higher rate of EBF at 6 months (adjusted odds ratio, 2.67 [95% CI, 1.45-4.91]) and a significantly lower rate of the introduction of solid foods before 4 months (adjusted odds ratio, 0.27 [95% CI, 0.08-0.94]). CONCLUSIONS AND RELEVANCE: An SMS intervention may be effective in promoting EBF, delaying the introduction of solid foods, increasing awareness of the World Health Organization breastfeeding guidelines, and improving knowledge of appropriate infant feeding practices for new mothers.