A novel prognostic risk-scoring system based on m5C methylation regulator-mediated patterns for glioma patients.

N5-methylcytosine (m5C) methylation modification plays a crucial role in the epigenetic mechanisms underlying tumorigenesis, aggressiveness, and malignancy in diffuse glioma. Our study aimed to develop a novel prognostic risk-scoring system to assess the impact of m5C modification in glioma patients. Initially, we identified two distinct m5C clusters based on the expression level of m5C regulators in The Cancer Genome Atlas glioblastoma (TCGA-GBM) dataset. Differentially expressed genes (DEGs) between the two m5C cluster groups were determined. Utilizing these m5C regulation-related DEGs, we classified glioma patients into three gene cluster groups: A, B, and C. Subsequently, an m5C scoring system was developed through a univariate Cox regression model, quantifying the m5C modification patterns utilizing six DEGs associated with disease prognosis. The resulting scoring system allowed us to categorize patients into high- or low-risk groups based on their m5C scores. In test (TCGA-GBM) and validation (Chinese Glioma Genome Atlas [CGGA]-1018 and CGGA-301) datasets, glioma patients with a higher m5C score consistently exhibited shorter survival durations, fewer isocitrate dehydrogenase (IDH) mutations, less 1p/19q codeletion and higher World Health Organization (WHO) grades. Additionally, distinct immune cell infiltration characteristics were observed among different m5C cluster groups and risk groups. Our study developed a novel prognostic scoring system based on m5C modification patterns for glioma patients, complementing existing molecular classifications and providing valuable insights into prognosis for glioma patients.

The therapeutic potential of PD-1/PD-L1 pathway on immune-related diseases: Based on the innate and adaptive immune components.

Currently, immunotherapy targeting programmed cell death 1 (PD-1) or programmed death ligand 1 (PD-L1) has revolutionized the treatment strategy of human cancer patients. Meanwhile, PD-1/PD-L1 pathway has also been implicated in the pathogenesis of many immune-related diseases, such as autoimmune diseases, chronic infection diseases and adverse pregnancy outcomes, by regulating components of the innate and adaptive immune systems. Given the power of the new therapy, a better understanding of the regulatory effects of PD-1/PD-L1 pathway on innate and adaptive immune responses in immune-related diseases will facilitate the discovery of novel biomarkers and therapeutic drug targets. Targeting this pathway may successfully halt or potentially even reverse these pathological processes. In this review, we discuss recent major advances in PD-1/PD-L1 axis regulating innate and adaptive immune components in immune-related diseases. We reveal that the impact of PD-1/PD-L1 axis on the immune system is complex and manifold and multi-strategies on the targeted PD-1/PD-L1 axis are taken in the treatment of immune-related diseases. Consequently, targeting PD-1/PD-L1 pathway, alone or in combination with other treatments, may represent a novel strategy for future therapeutic intervention on immune-related diseases.

A combined analysis of bulk and single-cell sequencing data reveals that depleted extracellular matrix and enhanced immune processes co-contribute to fluorouracil beneficial responses in gastric cancer.

Fluorouracil, also known as 5-FU, is one of the most commonly used chemotherapy drugs in the treatment of advanced gastric cancer (GC). Whereas, the presence of innate or acquired resistance largely limits its survival benefit in GC patients. Although accumulated studies have demonstrated the involvement of tumor microenvironments (TMEs) in chemo-resistance induction, so far little is known about the relevance of GC TMEs in 5-FU resistance. To this end, in this study, we investigated the relationship between TME features and 5-FU responses in GC patients using a combined analysis involving both bulk sequencing data from the TCGA database and single-cell RNA sequencing data from the GEO database. We found that depleted extracellular matrix (ECM) components such as capillary/stroma cells and enhanced immune processes such as increased number of M1 polarized macrophages/Memory T cells/Natural Killer T cells/B cells and decreased number of regulatory T cells are two important features relating to 5-FU beneficial responses in GC patients, especially in diffuse-type patients. We further validated these two features in the tumor tissues of 5-FU-benefit GC patients using immunofluorescence staining experiments. Based on this finding, we also established a Pro (63 genes) and Con (199 genes) gene cohort that could predict 5-FU responses in GC with an AUC (area under curve) score of 0.90 in diffuse-type GC patients, and further proved the partial applicability of this gene panel pan-cancer-wide. Moreover, we identified possible communications mediated by heparanase and galectin-1 which could regulate ECM remodeling and tumor immune microenvironment (TIME) reshaping. Altogether, these findings deciphered the relationship between GC TMEs and 5-FU resistance for the first time, as well as provided potential therapeutic targets and predicting rationale to overcome this chemo-resistance, which could shed some light on developing novel precision treatment strategies in clinical practice.

Hematological adaptations in diploid and triploid Salvelinus fontinalis and diploid Oncorhynchus mykiss (Salmonidae, Teleostei) in response to long-term exposure to elevated temperature.

Hematology is a simple but reliable method to determine the influence of environmental stressors on the physiology and performance of teleost fish. Understanding the detailed impacts of elevated temperature on the hematology of fish can help us to evaluate fish responses to climate change. Therefore, cellular and biochemical changes in peripheral blood were investigated in diploid (2n) and triploid (3n) brook trout and in 2n rainbow trout exposed to 20 °C for 32 days in comparison to fish acclimated to 9 °C. Additionally, survival and growth rates and the relative mRNA expression of heat-shock proteins were recorded. All brook trout and rainbow trout survived exposure to 20 °C. At 20 °C, growth was decreased in 2n rainbow trout, increased in 2n brook trout and similar to growth at 9 °C in 3n brook trout. The erythrocyte cell volume, nucleus volume, cell surface, and nucleocytoplasmatic ratio were significantly lower at 20 °C than at 9 °C in all investigated species/ploidy levels. In contrast, the erythrocyte surface-to-volume ratio was not affected by temperature. In 2n and 3n brook trout, erythrocyte concentration and blood hemoglobin content were increased at 20 °C; in 2n rainbow trout, there were no differences in comparison to 9 °C. Exposure of 2n and 3n brook trout and 2n rainbow trout to 20 °C had no negative effect on cellular and molecular immune components in blood. Serum diagnostic enzymes and metabolites indicated neither organ inflammation nor disease nor disturbance in energy metabolism or nutrition status in fish exposed to 20 °C. In addition, the mRNA expression of Hsp70 and Hsp90 relative to the 28S ribosomal protein S32 did not differ between 9 °C and 20 °C.

Food nutrients as inherent sources of immunomodulation during COVID-19 pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - a novel coronavirus has rapid spread, and caused community infection around the globe. During the absence of a vaccine, people focused more on an immunity-boosting diet and needed clear knowledge about immunity-boosting foods. However, after the vaccination drive, the importance of food as a natural source of immunomodulation cannot be neglected. So, the purpose of this review was to describe the role of vital nutrient in boosting immune system of body apart from other factors like adequate sleep, exercise, and low stress levels. Macrophages, neutrophils, natural killer cells, dendritic cells, B-cells, and T-cells are the important components having important role in maintaining immunity of the human body. The first four-act as the initial mediators of innate host defense, and the latter two produce antibodies for pathogen destruction. The review investigated vital nutrients like vitamin-C, A, E and D, iron, zinc, folic acid, probiotics, and prebiotics affecting these immune components in some extent. Fruits, vegetables, spices, herbs, seeds, nuts, cereals, millets, and superfoods like chlorella and spirulina are good sources of these nutrients. However, fortified foods, functional foods, encapsulated foods with bioactive compounds and plant-based foods have shown immense potential in boosting immunity against viral infections like COVID-19. Some clinical trials and retrospective cohort studies have shown reduction in the severity of COVID-19 patients with relation to plant-based diet, vitamin D and C doses, probiotic, and zinc salts application.

NOD1 activation induces oxidative stress via NOX1/4 in adipocytes.

Activation of innate immune components promotes cell autonomous inflammation in adipocytes. Oxidative stress links pattern recognition receptor-mediated detection of inflammatory ligands and the immune response. Reactive oxygen species (ROS) may mediate the effect of nucleotide-binding oligomerization domain protein-1 (NOD1) activation on inflammation in adipocytes. Here, we define the potential role of NADPH oxidase (NOX)-derived ROS in NOD1-mediated inflammatory response in adipocytes. Differentiated 3T3-L1 adipocytes were treated with NOD1 activating ligand D-gamma-Glu-meso-diaminopimelic acid (iE-DAP) to evaluate the oxidative stress and contribution of NOX as source of intracellular ROS. NOD1 activation potently induced ROS generation in 3T3-L1 adipocytes. Of the NOX family members, expression of NOX1 and NOX4 was increased upon NOD1 activation, in a PKCδ-dependent manner. siRNA-mediated down-regulation of NOX1 or NOX4 inhibited NOD1-mediated ROS production and increased the expression of antioxidant defense enzyme catalase and superoxide dismutase (SOD). siRNA-mediated lowering of NOX1 or NOX4 also suppressed NOD1-mediated activation of JNK1/2 and NF-κB, and consequent activation of inflammatory response in 3T3-L1 adipocytes. In summary, our findings demonstrate that NOD1 activation provokes oxidative stress in adipocytes via NOX1/4 and that oxidative stress, at least in part, contributes to induction of inflammatory response. Defining the source of ROS after immune response engagement may lead to new therapeutic strategies for adipose tissue inflammation.

Effects of Holder Pasteurization on Immune Composition of Human Milk.

Background: Human milk (HM) is the ideal food for newborn (NB) nutrition, it provides all macro and micronutrients for human growth and development and also contains bioactive compounds, which influence the development of the neonatal digestive and immune systems. The holder pasteurization process is essential to prevent NB infection from donated milk. Therefore, the aim of this study was to check whether or not holder pasteurization could impact the concentration of immune components in HM and the capacity to induce epithelial cell growth. Materials and Methods: The study was performed on raw and holder pasteurized (62.5°C/30 minutes) paired milk samples after submission to the freezing process in both phases. For cytokine and adipokine measurements, ELISA was performed on 40 individual samples of HM from single donors. For analyzes of epithelial cell growth, HuTu-80 cells were cultivated in Minimum Essential Eagle medium with 15% of raw or pasteurized milk, eight pairs of milk were used. Results: The results showed that no alteration was observed in the concentration of cytokine after milk holder pasteurization, and leptin concentration was reduced in holder pasteurized milk. The heat treatment also did not impact the capacity of breast milk to promote intestinal epithelial cell growth. Conclusions: The results showed that donated breast milk pasteurization has a small impact on the HM bioactive concentration compounds. This technique is important to avoid NB infection.