Ginsenoside Rg3 Sensitizes Colorectal Cancer to Radiotherapy through Downregulation of Proliferative and Angiogenic Biomarkers

Background. Radiation therapy is an important mode of colorectal cancer treatment. However, most people die of local recurrence after tumors become resistant to radiotherapy, and little progress has been made in treating radiotherapy-resistant colorectal cancer. Hence, novel agents that are nontoxic and can sensitize colorectal cancer to radiotherapy are urgently needed. Ginsenoside Rg3, a saponin extracted from ginseng, shows cytotoxicity against a variety of cancer cells through suppression of pathways linked to oncogenesis, including cell survival, proliferation, invasion, and angiogenesis. In this article, we investigated whether Rg3 can sensitize colorectal cancer to radiation in vivo. Methods and Materials. We established CT-26 xenografts in BALB/c mice and treated them with vehicle, Rg3, radiation, and combined Rg3 + radiation. Mouse quality of life, survival, tumor volumes, and inhibitive rates were estimated. NF-κB activation was ascertained using electrophoretic mobility shift assay and immunohistochemistry. We also tested for markers of proliferation, angiogenesis, and invasion using immunohistochemistry and Western blot analysis. Results. Rg3 significantly enhanced the efficacy of fractionated radiotherapy by improving the quality of life of mice. Moreover, tumors from mice xenografted with CT-26 cells and treated with combined Rg3 + radiotherapy showed significantly lower tumor volumes (P<0.01 versus controls; P<0.05 versus radiation alone), NF-κB activation, and expression of NF-κB-regulated gene products (cyclin D1, survivin, cyclooxygenase-2 (COX-2), and vascular endothelial growth factor (VEGF)) compared with controls. The combination treatment was also effective in suppressing angiogenesis, as indicated by lower CD31+ microvessel density compared with controls (P<0.05). Conclusion. Our results suggest that Rg3 enhances the antitumor effects of radiotherapy for colorectal cancer by suppressing NF-κB and NF-κB-regulated gene products, leading to inhibition of tumors and prolongation of the lifespan of CT-26 xenograft BALB/c mice

The effect of breakfast on childhood obesity: a systematic review and meta-analysis

ObjectivePrevious cohort trials have shown that skipping breakfast increases the risk of obesity or overweight in children. However, this finding remains controversial. Through a meta-analysis, this study systematically evaluated the effect of skipping breakfast on the prevalence of obesity or overweight in children.MethodsWe performed a literature search for studies published until March 19, 2023. using the Cochrane, PubMed, and Embase databases. Based on the inclusion and exclusion criteria, observational studies on the relationship between skipping breakfast and overweight/obesity in children and adolescents were analyzed. Three investigators independently screened the relevant literature, extracted the data, and assessed the risk of bias. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). A random-effects model was used. The odds ratio (OR) with its 95% confidence interval (CI) was used to indicate the effect size.ResultsA total of 40 retrospective studies with 323,244 children ranging in age from 2 to 20 years were included in this study. The results of this meta-analysis showed that children and adolescents who skipped breakfast had a significantly higher prevalence of obesity or overweight than those who ate breakfast (OR, 1.59; 95% CI, 1.33–1.90; P &lt; 0.001). Skipping breakfast was positively associated with overweight in children and adolescents (OR, 1.37; 95% CI, 1.23–1.54; P &lt; 0.001). Similarly, skipping breakfast was positively associated with obesity in children and adolescents (OR, 1.51; 95% CI, 1.30–1.76; P &lt; 0.001). The effect was also different by sex, with girls being the most affected (OR, 1.47; 95% CI, 1.23–1.76; P &lt; 0.001). There was also a correlation between skipping breakfast and abdominal obesity in children (OR, 0.65; 95% CI, 0.55–0.77; P &lt; 0.001).ConclusionThis meta-analysis suggested that skipping breakfast is associated with an increased risk of overweight/obesity in children and adolescents. The findings provide support for a possible protective role of breakfast against excessive weight gain in children and adolescents. However, more rigorous study designs with validated and standardized measures of relevant variables are needed

Increased expression of flotillin-2 protein as a novel biomarker for lymph node metastasis in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a head and neck malignant tumor rare throughout most of the world but common in Southeast Asia, especially in Southern China. Flotillin-2 (Flot-2) is not only an important component of cellular membrane, but also involves in various cellular processes such as membrane trafficking, T cell and B cell activation, regulation of several signaling pathways associated with cell growth and malignant transformation, keeping structure and junction of epidermal cells and formation of filopodia. Although such molecular effects of Flot-2 have been reported, whether the expression of Flot-2 protein is associated with clinicopathologic implication for NPC has not been reported. The purpose of this research is to investigate the expression of Flot-2 protein in NPC and control nasopharyngeal epithelial tissues by immunohistochemistry and elucidate the association between the expression of Flot-2 protein and clinicopathological characteristics of NPC. The results showed that the positive percentage of Flot-2 expression in the NPC, nasopharyngeal epithelia with atypical hyperplasia and in the control nasopharyngeal mucosa epithelia was 88.8% (119/134), 76.9% (10/13) and 5.7% (5/88), respectively. There was significantly higher expression of Flot-2 protein in NPC and nasopharyngeal epithelia with atypical hyperplasia compared to the control nasopharyngeal mucosa epithelia (P<0.001, respectively). The positive percentage of Flot-2 protein expression in NPC patients with lymph node metastasis was significantly higher than those without lymph node metastasis. Increasing of Flot-2 expression was obviously correlated with clinical stages of NPC patients. The expression of Flot-2 was proved to be the independent predicted factor for lymph node metastasis by multivariate analysis. The sensitivity of Flot-2 for predicting lymph node metastasis of NPC patients was 93%. Taken together, our results suggest that the increased expression of Flot-2 protein is a novel higher sensitivity biomarker that can predict lymph node metastases in NPC

Calcium-binding capacity of peptides obtained from sheep bone and structural characterization and stability of the peptide-calcium chelate

This study was aimed to obtain calcium-binding peptides with the enzymatic hydrolysis of sheep bone. The peptide of molecular weight from 3 to 10&nbsp;kDa (SBP3) obtained by alkaline protease had the highest calcium-binding capacities which were mainly due to high levels of residues of Asp, Glu, Arg, Lys, Ser, Leu and Phe. The optimal conditions for the preparation of peptide-calcium chelate (SBP3-Ca) were temperature of 50&nbsp;°C, pH value of 8, mass ratio of peptide/calcium of 3:1 for 55&nbsp;min by response surface methodology determined, under which calcium chelating rate of 89.56% was obtained. The spectral results showed that peptides are combined with calcium through the interaction between the amino nitrogen atom and carboxyl oxygen atom. The scanning electron microscope and particle size analyses demonstrated that after peptide was combined with calcium ions, the microstructure was changed and the spatial structure was folded, which reduced the particle size with the formation of irregular particles.SBP3-Ca exhibited excellent stability in the presence of oxalic acid, phytic acid and in vitro simulated gastrointestinal environment. The present study provides a basis for the utilization and development of sheep bone peptide calcium chelate as a functional ingredient

Kaplan-Meier overall survival curves of NPC patients with expression of p-Mnk1 and p-eIF4E protein and different clinicopathological characteristics.

<p>Kaplan-Meier analysis to plot the survival curve of all 272 NPC patients with expression of p-Mnk1 and p-eIF4E and different clinicopathological characteristics and statistical significance was assessed using the log-rank test. Fig. 3A. Kaplan-Meier curves showed worse overall survival for p-Mnk1–positive patients compared with p-Mnk1–negative patients (P<0.001, two sided). Fig. 3B. Kaplan-Meier curves showed worse survival for p-eIF4E–positive patients compared with p-eIF4E–negative patients (P = 0.004, two sided). Fig. 3C. NPC patients with clinical stage III and IV were significantly related to poor prognosis compared to those patients with clinical stage I and II (P = 0.003, two sided). Fig. 3D. NPC patients with lymph node metastasis were significantly related to poor prognosis compared to those patients without lymph node metastasis (P<0.001, two sided). Fig. 3E NPC patients with combination chemotherapy and radiotherapy were significantly related to good prognosis compared to patients with chemotherapy and radiotherapy alone (P = 0.006, two sided). Fig. 3F. Histological types of NPC patients were no significantly related to their prognosis (P>0.05, two sided).</p

Association between expression of p-Mnk1 and p-eIF4E protein and clinicopathological features of NPC (n = 272).

<p>Abbreviations: NS, non significant; DNKC: Differentiated non-keratinized carcinoma, UDC: Undifferentiated carcinoma; LN, lymph node; LN, LNM, lymph node metastasis.</p

Expression of p-Mnk1 and p-eIF4E protein in NPC and non-cancerous nasopharyngeal epithelial tissues was detected by immunohistochemistry.

<p>The expression of p-Mnk1 and p-eIF4E protein was detected by immunohistochemistry using specific antibodies as described in the section of materials and methods. Strong positive expression of p-Mnk1 was found in nuclei of NPC (Fig. 1A, 20×, IHC, AEC staining). Low and weak nuclear positive expression of p-Mnk1 was showed in the non-cancerous nasopharyngeal epithelial cells (Fig. 1B, 20×, IHC, AEC staining). Strong positive expression of p-eIF4E in the cytoplasm of NPC (Fig. 1C, 20×, IHC, AEC staining). Weak positive expression of p-eIF4E in the cytoplasm of the non-cancerous nasopharyngeal epithelial cells (Fig. 1D, 20×, IHC, AEC staining).</p

The pairwise association between expression of p-Mnk1 and p-eIF4E protein in the 272 cases of NPC.

<p>The pairwise association between expression of p-Mnk1 and p-eIF4E protein in the 272 cases of NPC.</p

The possible causal relationship between COVID-19 and imaging markers of cerebral small vessel disease: a Mendelian randomization study

Observational studies have suggested that SARS-CoV-2 infection may increase the burden of cerebral small vessel disease (CSVD). This study aims to explore the causal correlation between COVID-19 and the imaging markers of CSVD using Mendelian randomization (MR) methods. Summary-level genome-wide association study (GWAS) statistics for COVID-19 susceptibility, hospitalization, and severity were utilized as proxies for exposure. Large-scale meta-analysis GWAS data on three neuroimaging markers of white matter hyperintensity, lacunar stroke, and brain microbleeds, were employed as outcomes. Our primary MR analysis employed the inverse variance weighted (IVW) approach, supplemented by MR-Egger, weighted median, and MR-PRESSO methods. We also conducted multivariable MR analysis to address confounding bias and validate the robustness of the established causal estimates. Comprehensive sensitivity analyses included Cochran’s Q test, Egger-intercept analysis, MR-PRESSO, and leave-one-out analysis. The MR analysis revealed a significant causal correlation between the severity of COVID-19 and an increased risk of lacunar stroke, as demonstrated by the IVW method (ORivw = 1.08, 95% CI: 1.03–1.16, pivw = 0.005, FDR = 0.047). Nevertheless, no causal correlations were observed between COVID-19 susceptibility or hospitalization and any CSVD imaging markers. The robustness and stability of these findings were further confirmed by multivariable MR analysis and comprehensive sensitivity analyses. This study provides compelling evidence of a potential causal effect of severe COVID-19 on the incidence of lacunar stroke, which may bring fresh insights into the understanding of the comorbidity between COVID-19 and CSVD.</p