Prognostic Significance of Glycolysis-Related Genes in Lung Squamous Cell Carcinoma.

Lung squamous cell carcinoma (LUSC) is one of the most common malignancies. There is growing evidence that glycolysis-related genes play a critical role in tumor development, maintenance, and therapeutic response by altering tumor metabolism and thereby influencing the tumor immune microenvironment. However, the overall impact of glycolysis-related genes on the prognostic significance, tumor microenvironment characteristics, and treatment outcome of patients with LUSC has not been fully elucidated. We used The Cancer Genome Atlas (TCGA) dataset to screen glycolysis-related genes with prognostic effects in LUSC and constructed signature and nomogram models using Lasso and Cox regression, respectively. In addition, we analyzed the immune infiltration and tumor mutation load of the genes in the models. We finally obtained a total of glycolysis-associated DEGs. The signature model and nomogram model had good prognostic power for LUSC. Gene expression in the models was highly correlated with multiple immune cells in LUSC. Through this analysis, we have identified and validated for the first time that glycolysis-related genes are highly associated with the development of LUSC. In addition, we constructed the signature model and nomogram model for clinical decision-making.

Harnessing Oleanolic Acid and Its Derivatives as Modulators of Metabolic Nuclear Receptors.

Nuclear receptors (NRs) constitute a superfamily of ligand-activated transcription factors with a paramount role in ubiquitous physiological functions such as metabolism, growth, and reproduction. Owing to their physiological role and druggability, NRs are deemed attractive and valid targets for medicinal chemists. Pentacyclic triterpenes (PTs) represent one of the most important phytochemical classes present in higher plants, where oleanolic acid (OA) is the most studied PTs representative owing to its multitude of biological activities against cancer, inflammation, diabetes, and liver injury. PTs possess a lipophilic skeleton that imitates the NRs endogenous ligands. Herein, we report a literature overview on the modulation of metabolic NRs by OA and its semi-synthetic derivatives, highlighting their health benefits and potential therapeutic applications. Indeed, OA exhibited varying pharmacological effects on FXR, PPAR, LXR, RXR, PXR, and ROR in a tissue-specific manner. Owing to these NRs modulation, OA showed prominent hepatoprotective properties comparable to ursodeoxycholic acid (UDCA) in a bile duct ligation mice model and antiatherosclerosis effect as simvastatin in a model of New Zealand white (NZW) rabbits. It also demonstrated a great promise in alleviating non-alcoholic steatohepatitis (NASH) and liver fibrosis, attenuated alpha-naphthol isothiocyanate (ANIT)-induced cholestatic liver injury, and controlled blood glucose levels, making it a key player in the therapy of metabolic diseases. We also compiled OA semi-synthetic derivatives and explored their synthetic pathways and pharmacological effects on NRs, showcasing their structure-activity relationship (SAR). To the best of our knowledge, this is the first review article to highlight OA activity in terms of NRs modulation.

Overview of Ursolic Acid Potential for the Treatment of Metabolic Disorders, Autoimmune Diseases, and Cancers via Nuclear Receptor Pathways.

Nuclear receptors (NRs) form a family of druggable transcription factors that are regulated by ligand binding to orchestrate multifaceted physiological functions, including reproduction, immunity, metabolism, and growth. NRs represent attractive and valid targets for the management and treatment of a vast array of ailments. Pentacyclic triterpenes (PTs) are ubiquitously distributed natural products in medicinal and aromatic plants, of which ursolic acid (UA) is an extensively studied member, due to its diverse bio-pertinent activities against different cancers, inflammation, aging, obesity, diabetes, dyslipidemia, and liver injury. In fact, PTs share a common lipophilic structure that resembles NRs' endogenous ligands. Herein, we present a review of the literature on UA's effect on NRs, showcasing the resulting health benefits and potential therapeutic outcomes. De facto, UA exhibited numerous pharmacodynamic effects on PPAR, LXR, FXR, and PXR, resulting in remarkable anti-inflammatory, anti-hyperlipidemic, and hepatoprotective properties, by lowering lipid accumulation in hepatocytes and mitigating non-alcoholic steatohepatitis (NASH) and its subsequent liver fibrosis. Furthermore, UA reversed valproate and rifampicin-induced hepatic lipid accumulation. Additionally, UA showed great promise for the treatment of autoimmune inflammatory diseases such as multiple sclerosis and autoimmune arthritis by antagonizing RORγ. UA exhibited antiproliferative effects against skin, prostate, and breast cancers, partially via PPARα and RORγ pathways. Herein, for the first time, we explore and provide insights into UA bioactivity with respect to NR modulation.

Establishment and Systematic Evaluation of Gastric Cancer Classification Model Based on Pyroptosis.

Background: Gastric cancer (GC) is considered the fifth most prevalent type of cancer and the third leading cause of cancer deaths worldwide. This in-depth investigation was performed to generate fresh concepts for the clinical classification, diagnosis, and prognostic evaluation of GC. Methods: The data were retrieved from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Unsupervised cluster analysis was used to divide up the GC patients using pyroptosis-related differentially expressed genes (DEGs), which were discovered to be significantly linked with GC prognosis. The therapeutic importance of pyroptosis in GC patients was discovered using PCA analysis of genes associated with pyroptosis. The models were then carefully scrutinized. Results: Three hub genes, ELANE, IL6, and TIRAP, exhibit significant predictive importance among the 15 pyroptosis-related genes. Unsupervised clustering analysis revealed that the DEGs were enriched in the pathway of cytokine-cytokine receptor interactions, and Clusters 1 and 2 had statistically distinct prognoses. PCA analysis revealed significant differences in the area under the curve, immunological checkpoints, immunogenic cell death, and prognostic value between the high- and low-risk groups. Conclusions: These two GC classification models, based on pyroptosis, have significant clinical value for patients with GC.

Head and Neck Squamous Cell Carcinoma: NT5E Could Be a Prognostic Biomarker.

Head and neck squamous cell carcinoma (HNSCC) is a type of tumour with a relatively poor prognosis. In recent years, immune checkpoint inhibitors, such as CTLA-4 and PD-1/PDL-1 inhibitors, have improved the treatment status of advanced tumours. However, the emergence of drug resistance has brought difficulties to clinical treatment, and new immune checkpoint research is imminent. The hypoxia-adenosine pathway, in which CD73 encoded by the NT5E gene is a key enzyme for adenosine production, has been identified as an immune checkpoint of great potential. Therefore, NT5E may play an important role in HNSCC. We performed a detailed bioinformatics analysis of NT5E in HNSCC, and the results showed that the overexpression of NT5E in HNSCC was associated with poor prognosis. Our further investigation of the coexpression pattern of HNSCC could provide a reference for drug resistance and immunotherapy studies.

Single-Cell Sequencing Analysis Based on Public Databases for Constructing a Metastasis-Related Prognostic Model for Gastric Cancer.

Background: Although incidences of gastric cancer have decreased in recent years, the disease remains a significant danger to human health. Lack of early symptoms often leads to delayed diagnosis of gastric cancer, so that many patients miss the opportunity for surgery. Treatment for advanced gastric cancer is often limited. Immunotherapy, targeted therapy, and the mRNA vaccine have all emerged as potentially viable treatments for advanced gastric cancer. However, our understanding of the immune microenvironment of gastric cancer is far from sufficient; now is the time to explore this microenvironment. Methods: In our study, using TCGA dataset and the GEO dataset GSE62254, we performed in-depth transcriptome and single-cell sequencing analyses based on public databases. We analyzed differential gene expressions of immune cells in metastatic and nonmetastatic gastric cancer and constructed a prognostic model of gastric cancer patients based on these differential gene expressions. We also screened candidate vaccine genes for gastric cancer. Results: This prognostic model can accurately predict the prognosis of gastric cancer patients by dividing them into high-risk and low-risk groups. In addition to this, we identified a candidate vaccine gene for gastric cancer: PTPN6. Conclusions: Our study could provide new ideas for the treatment of gastric cancer.

Clinical Value of the Prognostic Nutrition Index in the Assessment of Prognosis in Critically Ill Patients with Stroke: A Retrospective Analysis.

Purpose: The purpose of study was to evaluate the association between prognostic nutritional index (PNI) and all-cause mortality of critically ill patients with stroke. Methods: Clinical data derived from Multiparameter Intelligent Monitoring in Intensive Care were analyzed. The primary endpoint was 30-day all-cause mortality; secondary endpoints were 90-day mortality and one-year cause mortality. The potential prognostic roles of PNI were analyzed by Cox proportional hazard models. The independent prognostic roles of PNI in the cases were analyzed by smooth curve fitting. Results: Concerning 30-day mortality, the HR (95% CI) for a high PNI (≥39.7) was 0.700 (0.544, 0.900; P = 0.00539), compared to a low PNI (<39.7). After adjusting for multiple confounders, the HR (95% CI) for a high PNI (≥39.7) was 0.732 (0.547, 0.978; P = 0.03514), compared to a low PNI (<39.7). Regarding 90-day and one-year mortality, a similar trend was observed. In addition, a nonlinear association between PNI and 30-day mortality was found. Using recursive algorithm and two-piecewise linear regression model, inflection point (IP) was calculated, which was 49.4. On the right side of the IP, there was a positive relationship between PNI and 30-day mortality, and the effect size, 95% CI, and P value were 1.04 (1.01, 1.07), P = 0.0429, respectively. On the left of the IP, the effect size, 95% CI, and P value were 0.97 (0.96, 0.99) and 0.0011, respectively. Conclusions: The PNI was an independent predicting factor of 30-day, 90-day, and 1-year mortality of the critically ill patients with stroke. In addition, there was a U-shaped relationship between PNI and all-cause mortality of stroke patients. PNI was a risk factor for the outcome of stroke when PNI was >49.4, while PNI was a protective factor for outcome of stroke when PNI was <49.4.

Utility of Circulating Cell-Free DNA in Assessing Microsatellite Instability and Loss of Heterozygosity in Breast Cancer Using Human Identification Approach.

The diagnostic and prognostic utility of circulating cell-free DNA (cfDNA) in breast cancer (BC) patients was recently reported. Here, we investigated the use of cfDNA to examine microsatellite instability (MSI) and loss of heterozygosity (LOH) for early BC diagnosis. cfDNA and genomic DNA from 41 female BC patients and 40 healthy controls were quantified using NanoDrop spectrophotometry and real-time PCR. The stability of genomic and cfDNA was assessed using a high-resolution AmpFlSTR MiniFiler human identification kit. Significant increases in cfDNA plasma concentrations were observed in BC patients compared to controls. The genotype distribution of the eight autosomal short tandem repeat (STR) loci D7S820, D13S317, D21S11, D2S1338, D18S51, D16S539, FGA, and CSF1PO were in Hardy-Weinberg equilibrium. Significant differences in the allele frequencies of D7S820 allele-8, D21S11 allele-29, allele-30.2, allele-32.2, and CSF1PO allele-11 were seen between BC patients and controls. LOH and MSI were detected in 36.6% of the cfDNA of patients compared to genomic DNA. This study highlights the utility of plasma-derived cfDNA for earlier, less invasive, and cost-effective cancer diagnosis and molecular stratification. It also highlights the potential value of cfDNA in molecular profiling and biomarkers discovery in precision and forensic medicine.

Assessment of health awareness and knowledge toward SARS-CoV-2 and COVID-19 vaccines among residents of Makkah, Saudi Arabia.

INTRODUCTION: Public awareness regarding COVID-19 plays an important role in controlling the virus' spread and treating infected people. A high level of awareness among the public will help to implement preventive measures, particularly in the most populated regions, such as Makkah, Saudi Arabia. COVID-19 is an infectious disease and the Saudi Arabian government has taken serious precautions and implemented several preventive measures. In addition, The Ministry of Health (MOH) has launched many awareness campaigns and provided COVID-19 vaccines for free. THE OBJECTIVES: To assess the Public's level of health awareness and knowledge toward SARS-CoV-2 and COVID-19 vaccines among residents of Makkah, Saudi Arabia. METHODS: A cross-sectional study was conducted in the Makkah region from February 23 to March 2, 2021. The questionnaire was generated using a Google form and distributed online through social platforms such as Twitter and WhatsApp. The questionnaire consisted of five sections and six hundred participants have answered and completed all questions. Then, All data were imported into Microsoft Excel and analyzed using the statistical tools SAS version 9.4 and SPSS version 25 software. RESULTS: A total of 600 participants from the Makkah region were found to have a high level of awareness and knowledge about all aspects of SARS-CoV-2 and the COVID-19 disease. For example, all participants considered coronavirus to be contagious, and 89.8% of them knew that COVID-19's symptoms are similar to those of seasonal flu. Most respondents showed a high level of awareness regarding the main factors of SARS-CoV-2 transmission. Over 98.7% of respondents were aware of the role of gatherings and events in further spread of the virus. The participants showed a good level of awareness about other preventive measures, such as maintaining social distancing and wearing a mask. However, the respondents considered COVID-19 vaccines to be effective, but some of them were not aware of their side effects, and 38.8% planned to receive a vaccine. CONCLUSION: The residents of Makkah showed a high level of awareness about these aspects; an excellent awareness level was noted for SARS-CoV-2, means of transmission, disease symptoms and prevention of viral spread. On the other hand, the participants had less knowledge regarding COVID-19 vaccines; hence, more effort is required to educate people about the safety and benefits of the vaccines.

The Impact of Addition Oats (Avena sativa) and Cinnamon on Cookies and their Biological Effects on Rats Treated with Cirrhosis by CCL4.

Oats are represented an important source for nutrition, and it have attracted a lot of attention in recent years. In this study we produced oatmeal cookies and oats was added to formula wheat by 50% and 75%. Also, we added cinnamon to treatments 3 and 4 by 5% to increase nutrition value of oatmeal cookies, improvement sensory evaluation and increase antioxidant properties. All the cookies treatments were storage at room temperature. The purposes of this study were to study antioxidant activity for oats and cinnamon. Also determined the chemical composition include (moisture content, protein, ash, total lipids, crude fibers, carbohydrates and total calories) for oats, white flour and oatmeal cookies treatments. In addition evaluated all of sensory evaluation contain (appearance, color, texture, taste and odor) and microbiological evaluation such as (total bacterial count, spore forming bacteria and mold and yeasts count) for oatmeal cookies treatments. Also, biological assays were preformed to measure level of GPT, GOT, urea, creatinine, total cholesterol, triglycerides, HDL, LDL, and glucose. Furthermore, histopathological examination of both liver and kidneys was analyzed. The obtained results were clarified that the antioxidant activity for oats and cinnamon were 52.91% and 87.91%. Moreover, addition of oats and cinnamon to the cookies improve sensory evaluation as made it more acceptable, decreasing microbial load principally treatments 4 (prepared by 75% oats + 5% cinnamon). Biochemical assays were improved in rats with cirrhosis of carbon tetrachloride and their histopathological examination of liver and kidneys. It was clear that the additions ground whole grain oats and cinnamon to wheat flour based cookies improve its nutritional, chemical, and biological functions properties.

RAGE Signaling in Melanoma Tumors.

Despite recent progresses in its treatment, malignant cutaneous melanoma remains a cancer with very poor prognosis. Emerging evidences suggest that the receptor for advance glycation end products (RAGE) plays a key role in melanoma progression through its activation in both cancer and stromal cells. In tumors, RAGE activation is fueled by numerous ligands, S100B and HMGB1 being the most notable, but the role of many other ligands is not well understood and should not be underappreciated. Here, we provide a review of the current role of RAGE in melanoma and conclude that targeting RAGE in melanoma could be an approach to improve the outcomes of melanoma patients.