Immunological Functions Research Articles

Metabolic dysregulation impairs lymphocyte function during severe SARS-CoV-2 infection

Cellular metabolic dysregulation is a consequence of SARS-CoV-2 infection that is a key determinant of disease severity. However, how metabolic perturbations influence immunological function during COVID-19 remains unclear. Here, using a combination of high-dimensional flow cytometry, cutting-edge single-cell metabolomics, and re-analysis of single-cell transcriptomic data, we demonstrate a global hypoxia-linked metabolic switch from fatty acid oxidation and mitochondrial respiration towards anaerobic, glucose-dependent metabolism in CD8+Tc, NKT, and epithelial cells. Consequently, we found that a strong dysregulation in immunometabolism was tied to increased cellular exhaustion, attenuated effector function, and impaired memory differentiation. Pharmacological inhibition of mitophagy with mdivi-1 reduced excess glucose metabolism, resulting in enhanced generation of SARS-CoV-2- specific CD8+Tc, increased cytokine secretion, and augmented memory cell proliferation. Taken together, our study provides critical insight regarding the cellular mechanisms underlying the effect of SARS-CoV-2 infection on host immune cell metabolism, and highlights immunometabolism as a promising therapeutic target for COVID-19 treatment.

Abstract 6174: ATX-101, a peptide drug targeting PCNA, enhances the effect of gemcitabine in liposarcoma and leiomyosarcoma

Abstract Soft tissue sarcomas are heterogeneous mesenchymal neoplasms and account for 1% of all cancers in adults. Over 50 sarcomas subtypes have been classified and many have very limited treatment options which include surgery, chemotherapy and radiation. Two of the most common sarcomas are liposarcoma and leiomyosarcoma which are often treated with chemotherapies such as doxorubicin, dacarbazine and gemcitabine with low response rates. There is now more than ever an urgent need for new therapies for sarcoma. PCNA (Proliferating Cell Nuclear Antigen) is considered to be a key regulator of DNA and cell cycle control. In addition, it has been implicated to have roles in metabolism, cellular signaling and some immunological functions. PCNA forms complexes with proteins bearing a novel PCNA-interacting Peptide Motif called APIM (AlkB homolog 2 PCNA Interacting Motif). This binding usually occurs during stress responses such as those achieved during cancer therapy or cancer development. By preventing stress proteins from repairing or defending themselves, cancer therapies can be made more effective. We examined the in vitro effects of ATX-101, a PCNA-APIM protein interaction blocking peptide, on liposarcoma cell lines LS141, DDLS, SW872, 93T449 and 94T778 and leiomyosarcoma cell lines SK-LMS, SK-UT1 and SK-UT-1B. Cell survival, as measured by cell proliferation assays, indicated IC50s of 7.5-15µM with ATX-101. Enhanced combination effects with ATX-101 and chemotherapies such as doxorubicin, irinotecan and gemcitabine were also observed by proliferation assay. Synergism, with ATX-101 and gemcitabine, was indicated with SynergyFinder analysis. Cell cycle changes exhibited increases of S and G2 phases when treated with ATX-101 and gemcitabine. This correlated with increase of cell cycle proteins, cyclin B1 and cyclin A2. Western blot observations included increase of apoptotic marker, cleaved caspase 3, and DNA damage marker, pH2A.X. In addition, immunofluorescence assay showed increasing pH2A.X with ATX-101 and gemcitabine. In vivo studies revealed ATX-101 enhanced gemcitabine decrease of tumor volume in leiomyosarcoma cell line xenograft, SK-UT1. Tumor target inhibition by western blot showed increased pH2A.X and cleaved PARP along with decreased RAD51 API protein with combination treatment. Taken these observations and results, there is strong evidence of combining gemcitabine with ATX-101 in liposarcoma and leiomyosarcoma. Citation Format: Elgilda Musi, Tahir Sheikh, Matthew Ingham, Sminu Bose, Gary K. Schwartz. ATX-101, a peptide drug targeting PCNA, enhances the effect of gemcitabine in liposarcoma and leiomyosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6174.

Proteomic cardiovascular risk assessment in chronic kidney disease.

Chronic kidney disease (CKD) is widely prevalent and independently increases cardiovascular risk. Cardiovascular risk prediction tools derived in the general population perform poorly in CKD. Through large-scale proteomics discovery, this study aimed to create more accurate cardiovascular risk models. Elastic net regression was used to derive a proteomic risk model for incident cardiovascular risk in 2182 participants from the Chronic Renal Insufficiency Cohort. The model was then validated in 485 participants from the Atherosclerosis Risk in Communities cohort. All participants had CKD and no history of cardiovascular disease at study baseline when ∼5000 proteins were measured. The proteomic risk model, which consisted of 32 proteins, was superior to both the 2013 ACC/AHA Pooled Cohort Equation and a modified Pooled Cohort Equation that included estimated glomerular filtrate rate. The Chronic Renal Insufficiency Cohort internal validation set demonstrated annualized receiver operating characteristic area under the curve values from 1 to 10 years ranging between 0.84 and 0.89 for the protein and 0.70 and 0.73 for the clinical models. Similar findings were observed in the Atherosclerosis Risk in Communities validation cohort. For nearly half of the individual proteins independently associated with cardiovascular risk, Mendelian randomization suggested a causal link to cardiovascular events or risk factors. Pathway analyses revealed enrichment of proteins involved in immunologic function, vascular and neuronal development, and hepatic fibrosis. In two sizeable populations with CKD, a proteomic risk model for incident cardiovascular disease surpassed clinical risk models recommended in clinical practice, even after including estimated glomerular filtration rate. New biological insights may prioritize the development of therapeutic strategies for cardiovascular risk reduction in the CKD population.

Innate Immune Response of TmToll-3 Following Systemic Microbial Infection in Tenebrio molitor.

Although Toll-like receptors have been widely identified and functionally characterized in mammalian models and Drosophila, the immunological function of these receptors in other insects remains unclear. Here, we explored the relevant innate immune response of Tenebrio molitor (T. molitor) Toll-3 against Gram-negative bacteria, Gram-positive bacteria, and fungal infections. Our findings indicated that TmToll-3 expression was mainly induced by Candida albicans infections in the fat bodies, gut, Malpighian tubules, and hemolymph of young T. molitor larvae. Surprisingly, Escherichia coli systemic infection caused mortality after TmToll-3 knockdown via RNA interference (RNAi) injection, which was not observed in the control group. Further analyses indicated that in the absence of TmToll-3, the final effector of the Toll signaling pathway, antimicrobial peptide (AMP) genes and relevant transcription factors were significantly downregulated after E. coli challenge. Our results indicated that the expression of almost all AMP genes was suppressed in silenced individuals, whereas the expression of relevant genes was positively regulated after fungal injection. Therefore, this study revealed the immunological involvement of TmToll-3 in T. molitor in response to systematic infections.

The novel putative methyltransferase METTL7A as one prognostic biomarker potentially associated with immune infiltration in human renal cancer

Among urological cancers, renal cancer has the highest fatality rate. In a previous pan-cancer study of the METTL family, we observed a stronger association between the METTL family members and the risk of renal cancer compared to other cancers. Among these members, METTL7A, a potential methyltransferase, was identified as a protective factor, although its role and mechanism in renal cancer remain unclear. In this study, we utilized public databases to examine the expression of METTL7A in renal cancer tissues and normal tissues and found that METTL7A expression was much lower in renal cancer tissues. We also noticed a link between low METTL7A expression and poor prognosis for patients. According to the results of our functional enrichment analysis, METTL7A may have a role in immunological functions in renal cancer. METTL7A expression was strongly linked with the degrees of immune cell infiltration and expression of numerous immunological components. METTL7A had significantly different effects on the survival times of renal cancer patients with high or low immune infiltration. Our findings suggest that METTL7A may be used as both a prognostic biomarker and an immunological target for kidney cancer. In conclusion, our study sheds light on the importance of METTL7A in renal cancer and emphasizes the potential of targeting METTL7A as a novel therapeutic strategy for kidney cancer.

The Effect of Echinacea Purpurea L. (Eastern Purple Coneflower) Essential Oil on Hematological Parameters and Gut Microbial Population of Zebrafish (Danio Rerio) With Aflatoxicosis

Background: Aflatoxin is one of the most important fungal toxins with documented hepatotoxic, teratogenic, and immunosuppressive properties. This mycotoxin is mainly produced by species of the genus Aspergillus in feed. Therefore, the application of compounds, which prevent complications of aflatoxins without losing feed quality, is highly beneficial. Objectives: This study aimed to determine the effect of the Echinacea purpurea L. essential oils on the regulation of the microbial population of the gastrointestinal tract and some blood factors of aflatoxin-fed zebrafish. Methods: Zebrafish were divided into four groups of 45 fish in three replicates: control (G1); G2, fish fed with feed containing 500 µg/kg E. purpurea L. essential oils; G3, fish fed with feed containing 500 µg/kg E. purpurea L. essential oil and 3 ppm aflatoxin B1(AFB1); and G4, fish fed with feed containing 3 ppm AFB1. The fish were fed with diets for 60 days. After this period, they were euthanized, blood was collected from the tail vein, and blood smears were prepared. Fish hepatopancreas were used to measure alanine aminotransferase, aspartate transaminase, and alkaline phosphatase enzymes with an auto-analyzer. Also, intestinal contents were cultured to evaluate microbial population. Results: Results showed that liver enzymes increased in the aflatoxin group (P<0.05), and concurrent use of the essential oil along with AFB1 reduced the liver enzymes compared with the AFB1-treated group. Moreover, AFB1 could convert the microbial population to pathogens. Differential blood counts in the G2 and G3 groups showed an increase in the percentages of neutrophils and thrombocytes. Conclusion: According to the results of this study, E. purpurea L. essential oils could reduce the adverse effects of chronic contamination with AFB1 in zebrafish. Nevertheless, more studies are needed to better understand the immunological function of E. purpurea L. in zebrafish and its mechanism of action against AFB1.

Transcutaneous electrical acupoint stimulation for immunologic function after surgery in patients with gastrointestinal tumor: a meta-analysis

ABSTRACT There is no consensus on whether transcutaneous acupoint electrical stimulation can be used to improve the immune function of postoperative patients with gastrointestinal tumors. This meta-analysis aims to evaluate the effects of transcutaneous electrical acupoint stimulation (TEAS) on postoperative immune function of patients with gastrointestinal tumor and provide evidence-based basis for clinical evaluation. The method used in this study is to systematically searched English databases including PubMed, Cochrane Library (CENTRAL), Excerpta Medica Database (EMbase), Web of Science and Chinese databases including Chinese National Knowledge Infrastructure (CNKI), Wanfang Data, VIP database and China Biomedical Literature Database (SinoMed). Relevant registration platform named Chinese Clinical Trial Registry (ChiCTR) was also searched. Manual search and document tracking are also performed. The aforementioned databases were retrieved for transcutaneous electrical acupoint stimulation for immunologic function after surgery in patients with gastrointestinal tumor randomized controlled trials (RCTs) from inception to 1 November 2022. Meta-analysis was conducted by RevMan5.4.1 software, and the evidence quality was evaluated using Cochrane risk bias evaluation form. In this study, a total of 18 trials with 1618 participants were analyzed. Only two studies were shown to be low risk. The results showed that there were significant differences in cellular immune and inflammatory factors and receptors, such as CD3+, CD4+, CD4+/CD8+, NK, IL-6, TNF-α, sIL-2 R, IL-2 and CRP, had significant effects (P < 0.05) after TEAS intervention on gastrointestinal tumor; however, CD8+ (P = 0.07) and IL-10 (P = 0.26) did not. Judging from the current evidence, TEAS was found to improve the immune function of patients with gastrointestinal tumors after surgery and reduce the level of inflammatory response, worthy of clinical promotion and use.

Hydroxy-Selenomethionine Mitigated Chronic Heat Stress-Induced Porcine Splenic Damage via Activation of Nrf2/Keap1 Signal and Suppression of NFκb and STAT Signal

Chronic heat stress (CHS) compromised the immunity and spleen immunological function of pigs, which may associate with antioxidant suppression and splenocyte apoptosis and splenic inflammation. Selenium (Se) exhibited antioxidant function and immunomodulatory through selenoprotein. Thus, this study aimed to investigate the protective effect of dietary hydroxy-selenomethionine (Selisso®, SeO) on chronic heat stress (CHS)-induced porcine splenic oxidative stress, apoptosis and inflammation. Growing pigs were raised in the thermoneutral environment (22 ± 2 °C) with the basal diet (BD), or raised in hyperthermal conditions (33 ± 2 °C) with BD supplied with 0.0, 0.2, 0.4 and 0.6 mg Se/kg SeO for 28 d, respectively. The results showed that dietary SeO supplementation recovered the spleen mass and enhanced the splenic antioxidant capacity of CHS growing pigs. Meanwhile, SeO activated the Nrf2/Keap1 signal, downregulated p38, caspase 3 and Bax, inhibited the activation of NFκb and STAT3, and enhanced the protein expression level of GPX1, GPX3, GPX4, SELENOS and SELENOF. In summary, SeO supplementation mitigates the CHS-induced splenic oxidative damages, apoptosis and inflammation in pigs, and the processes are associated with the activation of Nrf2/Keap1 signal and the suppression of NFκb, p38(MAPK) and STAT signal. It seems that the antioxidant-related selenoproteins (GPXs) and functional selenoproteins (SELENOS and SELENOF) play important roles in the alleviation processes.

An Evidence-Based Update on the Potential Association between Rheumatoid Arthritis and Lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) represents an uncommon disorder characterized by cystic lung destruction and chronic respiratory failure. Lung damage caused by various mechanisms may represent a hypothesis for studying the association between LAM and rheumatoid arthritis (RA), which is the most prevalent autoinflammatory rheumatic disease and may affect the lungs as an extra-articular manifestation. Despite their distinct clinical presentations, the pathophysiology of both disorders includes dysregulated immunological function, abnormal cellular development, and inflammation. Current research suggests a potential relationship between RA and LAM, as some RA patients have been reported to develop LAM. However, the association of RA and LAM raises important therapeutic dilemmas. For this reason, the trajectory of a patient who was identified in our medical records as suffering from both LAM and RA, treated with many novel molecules and biological therapy, but with a negative outcome due to respiratory and multiorgan failure, has been exemplified. The delay in the diagnosis of LAM is due to a correlation between RA and LAM, worsening the vital prognosis and also hindering pulmonary transplantation. In addition, extensive research is essential for understanding the potential connection between these two disorders and discovering any similar mechanisms involved that may underlie their occurrence. This may contribute to the development of new therapeutic options that target shared pathways implicated in the pathogenesis of RA and LAM.

Systematic pan-cancer analysis identifies gasdermin B as an immunological and prognostic biomarker for kidney renal clear cell carcinoma.

Gasdermin (GSDM)-mediated cell lytic death plays an essential role in immunity and tumorigenesis. Despite the association of gasdermin B (GSDMB) with the tumorigenesis of various cancers, whether GSDMB functions as a prognostic biomarker in renal cell carcinoma remains poorly understood. Here, we explored the potential immunological functions and the prognostic value of GSDMB across multiple tumors with The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, including analyzing the relationship between GSDMB expression and prognosis, tumor-immune system interactions, immunomodulators, and immune cell infiltration of different tumors. Importantly, elevated expression of GSDMB is an essential factor for the poor prognosis of kidney renal clear cell carcinoma (KIRC) patients, suggesting that it might be helpful to predict a survival benefit from a clinical therapy regimen. Furthermore, GSDMB expression promoted the level of CD4+ T-cell infiltration of the tumors but is significantly negatively associated with immature dendritic cells (iDCs) in KIRC. Additionally, we identified TNFRSF25 and TNFSF14 as immunostimulators highly correlated with GSDMB expression. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses showed that GSDMB and its interacting proteins might affect tumor growth through the serine metabolism pathway. Our current results demonstrate a promising therapeutic strategy targeting GSDMB and provide new insights into GSDMB as an immunological and prognostic biomarker for KIRC.

Systematic pan-cancer analysis identifies transmembrane protein 158 as a potential therapeutic, prognostic and immunological biomarker.

The purpose of this study was to investigate the expression significance, predictive value, immunologic function, and biological role of transmembrane protein 158 (TMEM158) in the development of pan-cancer. To achieve this, we utilized data from multiple databases, including TCGA, GTEx, GEPIA, and TIMER, to collect gene transcriptome, patient prognosis, and tumor immune data. We evaluated the association of TMEM158 with patient prognosis, tumor mutational burden (TMB), and microsatellite instability (MSI) in pan-cancer samples. We performed immune checkpoint gene co-expression analysis and gene set enrichment analysis (GSEA) to better understand the immunologic function of TMEM158. Our findings revealed that TMEM158 was significantly differentially expressed between most types of cancer tissues and their adjacent normal tissues and was associated with prognosis. Moreover, TMEM158 was significantly correlated with TMB, MSI, and tumor immune cell infiltration in multiple cancers. Co-expression analysis of immune checkpoint genes showed that TMEM158 was related to the expression of several common immune checkpoint genes, especially CTLA4 and LAG3. Gene enrichment analysis further revealed that TMEM158 was involved in multiple immune-related biological pathways in pan-cancer. Overall, this systematic pan-cancer analysis suggests that TMEM158 is generally highly expressed in various cancer tissues and is closely related to patient prognosis and survival across multiple cancer types. TMEM158 may serve as a significant predictor of cancer prognosis and modulate immune responses to various types of cancer.

Effects of aging and macrophages on mice stem Leydig cell proliferation and differentiation in vitro.

Testosterone plays a critical role in maintaining reproductive functions and well-beings of the males. Adult testicular Leydig cells (LCs) produce testosterone and are generated from stem Leydig cells (SLCs) during puberty through adulthood. In addition, macrophages are critical in the SLC regulatory niche for normal testicular function. Age-related reduction in serum testosterone contributes to a number of metabolic and quality-of-life changes in males, as well as age-related changes in immunological functions. How aging and testicular macrophages may affect SLC function is still unclear. SLCs and macrophages were purified from adult and aged mice via FACS using CD51 as a marker protein. The sorted cells were first characterized and then co-cultured in vitro to examine how aging and macrophages may affect SLC proliferation and differentiation. To elucidate specific aging effects on both cell types, co-culture of sorted SLCs and macrophages were also carried out across two ages. CD51+ (weakly positive) and CD51++ (strongly positive) cells expressed typical SLC and macrophage markers, respectively. However, with aging, both cell types increased expression of multiple cytokine genes, such as IL-1b, IL-6 and IL-8. Moreover, old CD51+ SLCs reduced their proliferation and differentiation, with a more significant reduction in differentiation (2X) than proliferation (30%). Age matched CD51++ macrophages inhibited CD51+ SLC development, with a more significant reduction in old cells (60%) than young (40%). Crossed-age co-culture experiments indicated that the age of CD51+ SLCs plays a more significant role in determining age-related inhibitory effects. In LC lineage formation, CD51+ SLC had both reduced LC lineage markers and increased myoid cell lineage markers, suggesting an age-related lineage shift for SLCs. The results suggest that aging affected both SLC function and their regulatory niche cell, macrophages.

Splenic stromal niches in homeostasis and immunity.

The spleen is a gatekeeper of systemic immunity where immune responses against blood-borne pathogens are initiated and sustained. Non-haematopoietic stromal cells construct microanatomical niches in the spleen that make diverse contributions to physiological spleen functions and regulate the homeostasis of immune cells. Additional signals from spleen autonomic nerves also modify immune responses. Recent insight into the diversity of the splenic fibroblastic stromal cells has revised our understanding of how these cells help to orchestrate splenic responses to infection and contribute to immune responses. In this Review, we examine our current understanding of how stromal niches and neuroimmune circuits direct the immunological functions of the spleen, with a focus on T cell immunity.

Programming Factors of Neonatal Intestinal Dysbiosis as a Cause of Disease.

The intestinal microbiota consists of trillions of bacteria, viruses, and fungi that achieve a perfect symbiosis with the host. They perform immunological, metabolic, and endocrine functions in the body. The microbiota is formed intrauterine. Dysbiosis is a microbiome disorder characterized by an imbalance in the composition of the microbiota, as well as changes in their functional and metabolic activities. The causes of dysbiosis include improper nutrition in pregnant women, hormone therapy, the use of drugs, especially antibiotics, and a lack of exposure to the mother's vaginal microbiota during natural birth. Changes in the intestinal microbiota are increasingly being identified in various diseases, starting in the early neonatal period into the adult period. Conclusions: In recent years, it has become more and more obvious that the components of the intestinal microbiota are crucial for the proper development of the immune system, and its disruption leads to disease.

Influence of Factors on the gastrointestinal microbiota of Pigs

A complete understanding of the dynamic distribution of the intestinal microbiota in pigs is essential because microorganisms play a fundamental role in physiological processes, immunity, and nutrient metabolism by the macroorganism. Disruption of the gut microbiome can cause inflammation, oxidative stress, and a cytokine storm. Gut microbiome dysfunction can be caused by short-term or long-term (environmental, nutritional, and stress) factors. The microbial ecosystem of the intestine is fundamental for the pig's proper nutrition, and physiological and immunological functions. However, the composition and function of a healthy microbial ecosystem have yet to be qualitatively and quantitatively determined to be used as a tool to maximize animal health and performance. As efforts are made to reduce the use of antibiotics in pig farming, the ability of the gut microbiota to increase disease resistance must be recognized. Generally, the genera Bacteroides, Escherichia, Clostridium, Lactobacillus, Fusobacterium, and Prevotella dominate in pre-weaning piglets. Then Prevotella and Aneriacter become the dominant genera, with Fusobacterium, Lactobacillus and Miscellaneous as relative minors in post-weaning piglets. Specific genera of bacteria, including Bacteroides, Prevotella, and Lactobacillus, can be detected in more than 90 % of pigs and three enterotypes – identified in animals of the same species but of different ages. This suggests the presence of a “core” microbiota in the gut of healthy pigs that may be a potential target for nutritional or health regulation. The scientists' scientific data help to determine the “optimal” gut microbial profile for evaluating or improving the performance and health status of pigs at different stages of growth. Although external and stochastic factors contribute to the individuality of the microbiota, the fundamental principles governing how environmental factors and host genetic factors combine to shape this complex ecosystem are largely unknown and require systematic study.

The Chemokine, CCL20, and Its Receptor, CCR6, in the Pathogenesis and Treatment of Psoriasis and Psoriatic Arthritis.

Chemokines represent a superfamily of immune-modulatory small protein molecules that regulate leukocyte migration to inflammatory sites through their chemoattractant and cell signaling properties. This review focuses on the immunological functions of the CCR6 chemokine receptor and is chemokine ligand, CCL20, that contribute to it role in inflammation in human psoriasis. Peer-reviewed relevant articles are searched and selected from 2000 to 2022 using the search engines including PubMed and Google Scholar. After selectively reviewing and evaluating over seventy articles, a comprehensive overview on the immunology of CCL20-CCR6 axis in psoriasis and psoriatic arthritis, the X-ray crystal structures of CCL20 monomers, and the potential of developing clinical therapies targeting this axis is summarized. Over the past decade, preclinical studies carried out in animal models of psoriasis involving agents targeting CCL20-CCR6 axis have yielded promising results. Other studies that this axis may play a role in a number of other autoimmune diseases, including rheumatoid arthritis, suggesting a rationale for further investigation into this key signaling/migratory pathway.

The many faces of parasite calreticulin.

Calreticulin from parasites and its vertebrate hosts share ~50% identity and many of its functions are equally conserved. However, the existing amino acid differences can affect its biological performance. Calreticulin plays an important role in Ca2+ homeostasis and as a chaperone involved in the correct folding of proteins within the endoplasmic reticulum. Outside the endoplasmic reticulum, calreticulin is involved in several immunological functions such as complement inhibition, enhancement of efferocytosis, and immune upregulation or inhibition. Several parasite calreticulins have been shown to limit immune responses and promote infectivity, while others are strong immunogens and have been used for the development of potential vaccines that limit parasite growth. Furthermore, calreticulin is essential in the dialogue between parasites and hosts, inducing Th1, Th2 or regulatory responses in a species-specific manner. In addition, calreticulin participates as initiator of endoplasmic reticulum stress in tumor cells and promotion of immunogenic cell death and removal by macrophages. Direct anti-tumoral activity has also been reported. The highly immunogenic and pleiotropic nature of parasite calreticulins, either as positive or negative regulators of the immune response, render these proteins as valuable tools to modulate immunopathologies and autoimmune disorders, as well as a potential treatment of neoplasms. Moreover, the disparities in the amino acid composition of parasite calreticulins might provide subtle variations in the mechanisms of action that could provide advantages as therapeutic tools. Here, we review the immunological roles of parasite calreticulins and discuss possible beneficial applications.

Identifying Oxidized Lipid Metabolism-Related LncRNAs as Prognostic Biomarkers of Head and Neck Squamous Cell Carcinoma.

The relationship between oxidized lipid metabolism and the immunological function of cancer is well known. However, the functions and regulatory mechanisms of lncRNAs associated with oxidized lipid metabolism in head and neck squamous cell carcinoma (HNSCC) remain to be fully elucidated. In this study, we established an oxidized lipid metabolism-related lncRNA prognostic signature to assess the prognosis and immune infiltration of HNSCC patients. The HNSCC transcriptome was obtained from The Cancer Genome Atlas. The choice of the target genes with a relevance score greater than 10 was performed via a correlation analysis by GeneCards. Patients were categorized by risk score and generated with multivariate Cox regression, which was then validated and evaluated using the Kaplan-Meier analysis and time-dependent receiver operating characteristics (ROC). A nomogram was constructed by combining the risk score with the clinical data. We constructed a risk score with 24 oxidized lipid metabolism-related lncRNAs. The areas' 1-, 2-, and 3-year OS under the ROC curve (AUC) were 0.765, 0.724, and 0.724, respectively. Furthermore, the nomogram clearly distinguished the survival probabilities of patients in high- and low-risk groups, between which substantial variations were revealed by immune infiltration analysis. The results supported the fact that oxidized lipid metabolism-related lncRNAs might predict prognoses and assist with differentiating amid differences in immune infiltration in HNSCC.

Obesity and Wound Healing: Focus on Mesenchymal Stem Cells.

Chronic wounds represent nowadays a major challenge for both clinicians and researchers in the regenerative setting. Obesity represents one of the major comorbidities in patients affected by chronic ulcers and therefore diverse studies aimed at assessing possible links between these two morbid conditions are currently ongoing. In particular, adipose tissue has recently been described as having metabolic and endocrine functions rather than serving as a mere fat storage deposit. In this setting, adipose-derived stem cells, a peculiar subset of mesenchymal stromal/stem cells (MSCs) located in adipose tissue, have been demonstrated to possess regenerative and immunological functions with a key role in regulating both adipocyte function and skin regeneration. The aim of the present review is to give an overview of the most recent findings on wound healing, with a special focus on adipose tissue biology and obesity.

The Effect of Developmental Pleiotropy on the Evolution of Insect Immune Genes.

The pressure to survive ever-changing pathogen exposure explains the frequent observation that immune genes are among the fastest evolving in the genomes of many taxa, but an intriguing proportion of immune genes also appear to be under purifying selection. Though variance in evolutionary signatures of immune genes is often attributed to differences in gene-specific interactions with microbes, this explanation neglects the possibility that immune genes participate in other biological processes that could pleiotropically constrain adaptive selection. In this study, we analyzed available transcriptomic and genomic data from Drosophila melanogaster and related species to test the hypothesis that there is substantial pleiotropic overlap in the developmental and immunological functions of genes involved in immune signaling and that pleiotropy would be associated with stronger signatures of evolutionary constraint. Our results suggest that pleiotropic immune genes do evolve more slowly than those having no known developmental functions and that signatures of constraint are particularly strong for pleiotropic immune genes that are broadly expressed across life stages. These results support the general yet untested hypothesis that pleiotropy can constrain immune system evolution, raising new fundamental questions about the benefits of maintaining pleiotropy in systems that need to rapidly adapt to changing pathogen pressures.