The Prognosis Performance of a Neutrophil- and Lymphocyte-Associated Gene Mutation Score in a Head and Neck Cancer Cohort.

The treatment of head and neck squamous cell carcinomas (HNSCCs) is multimodal, and chemoradiotherapy (CRT) is a critical component. However, the availability of predictive or prognostic markers in patients with HNSCC is limited. Inflammation is a well-documented factor in cancer, and several parameters have been studied, with the neutrophil-to-lymphocyte ratio (NLR) being the most promising. The NLR is the most extensively researched clinical biomarker in various solid tumors, including HNSCC. In our study, we collected clinical and next-generation sequencing (NGS) data with targeted sequencing information from 107 patients with HNSCC who underwent CRT. The difference in the NLR between the good response group and the poor response group was significant, with more patients having a high NLR in the poor response group. We also examined the genetic alterations linked to the NLR and found a total of 41 associated genes across eight common pathways searched from the KEGG database. The overall mutation rate was low, and there was no significant mutation difference between the low- and high-NLR groups. Using a multivariate binomial generalized linear model, we identified three candidate genes (MAP2K2, MAP2K4, and ABL1) that showed significant results and were used to create a gene mutation score (GMS). Using the NLR-GMS category, we noticed that the high-NLR-GMS group had significantly shorter relapse-free survival compared to the intermediate- or low-NLR-GMS groups.

High G9a Expression in DLBCL and Its Inhibition by Niclosamide to Induce Autophagy as a Therapeutic Approach.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a malignant lymphoid tumor disease that is characterized by heterogeneity, but current treatment does not benefit all patients, which highlights the need to identify oncogenic genes and appropriate drugs. G9a is a histone methyltransferase that catalyzes histone H3 lysine 9 (H3K9) methylation to regulate gene function and expression in various cancers. METHODS: TCGA and GTEx data were analyzed using the GEPIA2 platform. Cell viability under drug treatment was assessed using Alamar Blue reagent; the interaction between G9a and niclosamide was assessed using molecular docking analysis; mRNA and protein expression were quantified in DLBCL cell lines. Finally, G9a expression was quantified in 39 DLBCL patient samples. RESULTS: The TCGA database analysis revealed higher G9a mRNA expression in DLBCL compared to normal tissues. Niclosamide inhibited DLBCL cell line proliferation in a time- and dose-dependent manner, reducing G9a expression and increasing p62, BECN1, and LC3 gene expression by autophagy pathway regulation. There was a correlation between G9a expression in DLBCL samples and clinical data, showing that advanced cancer stages exhibited a higher proportion of G9a-expressing cells. CONCLUSION: G9a overexpression is associated with tumor progression in DLBCL. Niclosamide effectively inhibits DLBCL growth by reducing G9a expression via the cellular autophagy pathway; therefore, G9a is a potential molecular target for the development of therapeutic strategies for DLBCL.

Emodin Ameliorates the Efficacy of Carfilzomib in Multiple Myeloma Cells via Apoptosis and Autophagy.

BACKGROUND: Carfilzomib, the proteasome inhibitor, can increase the overall survival rate of multiple myeloma (MM) patients undergoing targeted therapy. However, relapse and toxicity present great challenges for such treatment, so an urgent need for effective combination therapy is necessary. Emodin is a natural chemical compound that inhibits the proliferation of various cancers and can effectively combine with other treatments. In this study, we evaluated the sensitizing effect of emodin combined with carfilzomib on MM cells. METHODS: The cells were treated with emodin, carfilzomib, and a combination of drugs to determine their effects on cell proliferation and viability. The cell cycle distribution and reactive oxygen species (ROS) expression were measured by flow cytometry. The level of RNA and protein were analyzed through real-time qPCR and immunoblotting. RESULTS: Emodin acted synergistically with carfilzomib to reduce the proliferation and viability of MM cell lines in vitro. Furthermore, the combination of emodin and carfilzomib increased ROS production, inducing apoptosis and autophagy pathways via caspase-3, PARP, p62, and LC3B. CONCLUSIONS: These results provide a molecular target for combination therapy in MM patients.

Nutrition, Physical Exercise, and the Prevalence of Sarcopenia in Elderly Residents in Nursing Homes in China.

BACKGROUND This study aimed to investigate the factors associated with sarcopenia in elderly residents in three nursing homes in Suzhou City, East China including the association with nutrition and physical exercise. MATERIAL AND METHODS Elderly residents (n=316) from three nursing homes included 112 men and 204 women. The appendicular skeletal muscle index (ASMI), grip strength, and movements were measured to diagnose sarcopenia. The correlation between sarcopenia with age, sex, body mass index (BMI), ASMI, upper arm circumference, calf circumference, muscle content, grip strength, dietary intake, degree and duration of movement were also assessed. RESULTS The prevalence of sarcopenia was 28.8% (30.4% for men and 27.9% for women). Patients with sarcopenia were older compared with controls. Height, BMI, upper arm circumference, calf circumference and arm muscle mass, lower limb muscle mass, limb skeletal muscle index and ASMI, grip strength, and pace of movement were lower than controls. The prevalence of sarcopenia correlated with the intake of meat, fish, eggs, and milk, and duration of weekly aerobic and resistance exercise. Logistic regression analysis showed a positive correlation between the prevalence of sarcopenia and age, and a negative correlation between BMI and consumption of meat, eggs, and milk. CONCLUSIONS The prevalence of sarcopenia in elderly residents in three nursing homes in Suzhou City was 28.8%. Increasing age was a risk factor for sarcopenia. Increased BMI and a diet containing meat, eggs, and milk were protective factors. The findings from this study provide support that adequate dietary protein can prevent sarcopenia in the elderly.