Markers Of Immune Response Research Articles

First, do no harm: the role of preclinical animal models in predicting adverse events in gene therapy clinical trials for Duchenne muscular dystrophy and X-Linked myotubular myopathy

The occurrence of severe adverse events (SAEs) in patients with Duchenne muscular dystrophy (DMD), X-linked myotubular myopathy (XLMTM), and other neuromuscular diseases treated with adeno-associated virus (AAV) constructs has prompted studies to improve the safety and efficacy of gene therapy. Physicians have weighed the medical tenet of “first, do no harm” against the perspective of patients with progressive life-threatening conditions who may accept greater risk. Regarding SAE pathogenesis, discussion has focused on total AAV exposure and patient mutations more likely to induce immunity, while stressing the limitations of animal models in predicting adverse events. Therapeutic strategies for reducing side effects have employed more myotropic AAV serotypes and efficient transgenes. Other recommendations include excluding certain DMD gene mutations associated with SAEs and substituting less immunogenic transgenes such as utrophin (DMD) and myotubularin-related protein (XLMTM). For the sake of preclinical studies, emphasis has been placed on outbred rodents and larger animals that better predict immunity. Here, the absence of side effects in canine DMD and XLMTM models might be explained partly by phenotypic differences between affected humans and dogs. Specifically, dystrophin- and myotubularin-deficient dogs exhibit milder lesions, including less muscle fat deposition and the absence of hepatopathy, respectively, which could lead to reduced immune responses to AAV constructs. To better predict future problems, thought should be given to tracking early subclinical markers of the innate immune response, especially complement activation. Regardless of steps taken to improve the predictive value of animal models for SAEs, some questions will only be answered through human clinical trials after carefully considering the risk-benefit ratio.

Regulation of cell-mediated immune responses in dairy bulls via long non-coding RNAs from submandibular lymph nodes, peripheral blood, and the spleen

Cell-mediated immune responses (CMIRs) are critical to building a robust immune system and reducing disease susceptibility in cattle. Long non-coding RNAs (lncRNAs) regulate various biological processes. However, to the best of our knowledge, the characterization and functions of lncRNAs and their regulations on the bovine CMIR have not been investigated comprehensively. In this study, experimental bulls were immunized with a heat-killed preparation of Candida albicans (HKCA) to induce delayed-type hypersensitivity (DTH). Three bulls were classified as high- CMIR responders and three were low-CMIR responders, based on their classical DTH skin reactions. LncRNAs were identified in the submandibular lymph nodes, peripheral blood, and spleen of high- and low-CMIR animals using strand-specific RNA sequencing. A total of 21,003 putative lncRNAs were identified across tissues, and 420, 468, and 599 lncRNAs were differentially expressed between the two groups in the submandibular lymph node, peripheral blood, and spleen tissues, respectively. Functional analysis of the differentially expressed lncRNA (DElncRNA) target genes showed that a number of immune-related Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched, including immune response, cell adhesion, nucleosome, DNA packaging, antigen processing and presentation, and complement and coagulation cascades. Tissue specificity analysis indicated that lncRNA transcripts have stronger tissue specificity than mRNA. Furthermore, an interaction network was constructed based on DElncRNAs and DEGs, and 11, 14, and 11 promising lncRNAs were identified as potential candidate genes influencing immune response regulation in submandibular lymph nodes, peripheral blood, and spleen tissues, respectively. These results provide a foundation for further research into the biological functions of lncRNAs associated with bovine CMIR and identify candidate lncRNA markers for cell-mediated immune responses.

Association of Major Histocompatibility Complex Polymorphism With Acute Phase Response in Broiler Chicken.

Stress associated with changes in host immunity occurs in response to altered environmental conditions, endogenous imbalances, infectious agents and harmful stimuli. The importance of genetic diversity in chickens has increased due to individual immune differences towards resistance and susceptibility to various stimuli. This study aimed to investigate the association of major histocompatibility complex (MHC) polymorphism with acute phase response (APR) in Ross 308 broiler chickens. The allelic diversity of the LEI0258 microsatellite marker was determined in 120 Ross broilers. In addition, acute phase proteins (APPs), including serum amyloid A (SAA) and alpha-1-acid glycoprotein (AGP), were analysed as markers of the APR. Furthermore, leukocyte count and the heterophil/lymphocyte ratio (H/L ratio) were examined. The antibody response to the Newcastle disease vaccine (NDV) was also measured to assess humoral mediated immunity. Lastly, the correlation between immune responses and MHC alleles was investigated to identify the most effective alleles in a stress-related situation. A total of six alleles, ranging from 195 to 448bp, were identified. Association study revealed a significant influence of MHC alleles on APPs in Ross population (p<0.05). Notably, Allele 448 had a significant correlation with SAA concentration and the H/L ratio. Allele 207 displayed a positive association with AGP concentration, whereas Allele 195 showed a negative association. Furthermore, a significant association was observed between Allele 448 and basopenia, as well as between Allele 195 and monocytosis. Results confirmed the significance of MHC as a candidate gene marker for immune responses, which supports its use for vaccine design, genetic improvement of disease-resistant traits and resource conservation in commercial broiler chickens.

Breakthrough in allergy mitigation using an innovative steam pressure-based processing technique

Peanuts are recognized as one of the most common allergenic foods, known to induce severe Th2-mediated allergic reactions. The resulting global health concern has fostered the necessity to design innovative technologies capable of mitigating allergenicity. This study investigated the effect of an innovative thermomechanical process, “Intensification of Vaporization by Decompression to the Vacuum” (IVDV), on the protein content and immunogenicity of whole peanuts. Through animal studies using peanut allergy BALB/c mouse models, this research revealed a clear reduction in allergic symptoms once challenged with IVDV-treated peanut protein extract, compared to those receiving raw or deep-fried peanut protein extracts. Significant changes in immune response markers in animals were observed, including reduced levels of histamine, Th1/Th2 cytokines, and antibodies, thus confirming the efficacy of IVDV in mitigating allergenicity in peanuts. Saturated steam pressure was demonstrated to have a highly significant positive effect on the reduction of protein content in IVDV-treated samples through degradation, with a noteworthy reduction ranging from 42.3% to 89.2%. This pilot study embarked on a pioneering exploration into the ability of IVDV to offer a viable solution in reducing peanut allergenicity, opening new avenues for enhanced food safety and inclusivity. The ease of scalability of IVDV technology to an industrial level, along with its cost-efficiency, further enhance its appeal for widespread adoption.

PAARH promotes M2 macrophage polarization and immune evasion of liver cancer cells through VEGF protein

ObjectiveThis study aims to investigate the mechanism by which PAARH promotes M2 macrophage polarization and immune evasion of liver cancer cells through VEGF, in order to reveal its role in the progression of liver cancer. MethodsThe expressions of PAARH, VEGF, and HIF-1α in liver cancer cells were detected using qRT-PCR and Western blot. Flow cytometry was utilized to analyze the polarization status of macrophages and assess the impact on immune evasion-related markers. The relationship between PAARH and VEGF in macrophage polarization was further explored. Additionally, a tumor-bearing mouse model was established to observe tumor growth. ResultsThe results show that PAARH is upregulated in liver cancer cells, and silencing PAARH significantly inhibits tumor malignancy progression. Under hypoxic conditions, overexpression of PAARH significantly increases VEGF expression, and PAARH regulates M2 macrophage polarization through VEGF. Overexpression of PAARH significantly promotes M2 macrophage polarization, increases levels of PD-L1 and Th2 immune response markers, and enhances cell proliferation, migration, and invasion; it also suppresses M1 macrophage polarization, decreases levels of PD-L2 and Th1 immune response markers, and inhibits cell apoptosis. Silencing VEGF reverses these effects. Silencing PAARH or overexpressing VEGF weakens the malignant phenotype of the cells and immune evasion. Results from the tumor-bearing mouse model indicate that silencing PAARH significantly reduces tumor size and weight, while overexpressing VEGF significantly increases tumor volume and weight. ConclusionPAARH enhances the immune evasion capability of liver cancer cells by upregulating VEGF to promote M2 macrophage polarization, suggesting that PAARH may serve as a new therapeutic target for liver cancer.

A study of pre- and post-treatment hematologic markers of immune response in patients undergoing radiotherapy for soft tissue sarcoma.

This study investigates the impact of pre- and post-treatment hematologic markers, specifically neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), on treatment outcomes in soft tissue sarcoma (STS) patients undergoing radiation therapy (RT). Data from 64 patients who underwent RT for curative management of STS were reviewed. Pre-RT and post-RT hematologic measures were evaluated for associations with survival outcomes. A normal tissue complication probability (NTCP) curve for predicting ΔPLR ≥ 75 was modeled using a probit function. Elevated baseline NLR was associated with worse overall survival (OS) and disease-free survival (DFS), while elevated PLR was associated with worse DFS. Post-RT, elevated PLR was linked to worse OS and DFS. Increasing PLR change post-RT was associated with worse OS and DFS. Receiver operating characteristics analysis determined ΔPLR ≥ 75 to be a robust cutoff associated with worse DFS. Bone V10Gy ≥362 cc corresponded to a 50% risk of developing ΔPLR ≥ 75. These results suggest that hematologic markers could serve as prognostic biomarkers in both pre- and post-treatment settings for STS patients undergoing RT. Future studies can consider using bone V10Gy < 362 cc as a potential cutoff to reduce the risk of increased PLR after RT.

Histone demethylase enzymes KDM5A and KDM5B modulate immune response by suppressing transcription of endogenous retroviral elements.

The histone demethylases KDM5A and KDM5B are transcriptional repressors that play an important role in cancer and immune response, making them attractive drug targets. Unfortunately, small molecule inhibitors, including CPI-455, that block KDM5A and KDM5B enzymatic activity, have shown only limited effectiveness at suppressing cancer cell viability as single agents in vitro. In this study we undertook a multi-omics approach to map transcriptional and chromatin changes in KDM5A and KDM5B deficient cells compared to those treated with CPI-455. The datasets revealed that KDM5A and KDM5B modulate the expression of KRAB-ZNF genes and that loss of either gene was associated with increased expression of ERV genes and upregulation of immune response markers. Surprisingly, pharmacological inhibition of these enzymes did not phenocopy genetic ablation. In contrast, acute degradation of KDM5A using a dTAG system caused an increase in ERV expression, providing evidence that this immune modulation is independent of demethylase activity. Together with the limited success of small molecule inhibitors, our data provide strong rationale for the development of KDM5A and KDM5B degraders to modulate tumor immune responses.

Pan-immune-inflammation value as a prognostic biomarker for colon cancer and its variation by primary tumor location.

A growing body of research indicates significant differences between left-sided colon cancers (LCC) and right-sided colon cancers (RCC). Pan-immune-inflammation value (PIV) is a systemic immune response marker that can predict the prognosis of patients with colon cancer. However, the specific distinction between PIV of LCC and RCC remains unclear. To investigate the prognostic and clinical significance of PIV in LCC and RCC patients. This multicenter retrospective cohort study included 1510 patients with colon cancer, comprising 801 with LCC and 709 with RCC. We used generalized lifting regression analysis to evaluate the relative impact of PIV on disease-free survival (DFS) in these patients. Kaplan-Meier analysis, as well as univariate and multivariate analyses, were used to examine the risk factors for DFS. The correlation between PIV and the clinical characteristics was statistically analyzed in these patients. A total of 1510 patients {872 female patients (58%); median age 63 years [interquartile ranges (IQR): 54-71]; patients with LCC 801 (53%); median follow-up 44.17 months (IQR 29.67-62.32)} were identified. PIV was significantly higher in patients with RCC [median (IQR): 214.34 (121.78-386.72) vs 175.87 (111.92-286.84), P < 0.001]. After propensity score matching, no difference in PIV was observed between patients with LCC and RCC [median (IQR): 182.42 (111.88-297.65) vs 189.45 (109.44-316.02); P = 0.987]. PIV thresholds for DFS were 227.84 in LCC and 145.99 in RCC. High PIV (> 227.84) was associated with worse DFS in LCC [PIV-high: Adjusted hazard ratio (aHR) = 2.39; 95% confidence interval: 1.70-3.38; P < 0.001] but not in RCC (PIV-high: aHR = 0.72; 95% confidence interval: 0.48-1.08; P = 0.114). These findings suggest that PIV may predict recurrence in patients with LCC but not RCC, underscoring the importance of tumor location when using PIV as a colon cancer biomarker.

Spermidine supplementation influence on protective enzymes of Apis mellifera (Hymenoptera: Apidae).

Dietary supplementation has been proposed as a sustainable way to improve the health and resilience of honey bees (Apis mellifera, L.), as the decline in their numbers in recent decades has raised scientific, environmental, and economic concerns. Spermidine, a natural polyamine, has been shown to be a promising substance for honey bee supplementation, as its health-promoting effects have been demonstrated in numerous studies and in different organisms. As already shown, supplementation with spermidine at a certain concentration prolonged lifespan, reduced oxidative stress, and increased antioxidative capacity in honey bees. The aim of the present study was to investigate whether spermidine supplementation affects gene expression and/or enzyme activity of antioxidative and detoxification enzymes and immune response markers in honey bee workers. The different gene expression and enzyme activity patterns observed in abdominal and head tissues in response to spermidine supplementation suggest tissue-specific and concentration-dependent effects. In addition, the immune response markers suggest that spermidine has the ability to boost honey bee immunity. The observed changes make a valuable contribution to understanding the molecular mechanisms by which spermidine may exert its beneficial effects on the bee's health and lifespan. These results support the idea of the use of spermidine supplementation to promote bee health and resilience to environmental stressors, emphasizing that the dose must be carefully chosen to achieve a balance between the pro- and antioxidant effects of spermidine.

144P Analysis of a novel predictive marker of immune checkpoint response in head and neck cancer, calculated from histopathological slides through inferred transcriptomics

144P Analysis of a novel predictive marker of immune checkpoint response in head and neck cancer, calculated from histopathological slides through inferred transcriptomics

Exploring the impact of high salinity and parasite infection on antioxidant and immune systems in Coris julis in the Pityusic Islands (Spain)

Climate change associated with human activities alters marine ecosystems and causes imbalances and abrupt changes in sea conditions. Scarce freshwater resources for human consumption often prompt the construction of desalination plants, which discharge significant amounts of brine into the sea, potentially elevating salinity levels. Furthermore, global trade together with higher temperature and pollution can facilitate the spread of parasites. The aim of this study was to assess the potential effects of salinity, an abiotic stressor, and Scaphanocephalus sp. parasitic infection responsible for black spot disease, a biotic stressor, on Coris julis, a common fish in the Balearic Islands (Spain). Fish were sampled from an area affected by a desalination plant, one with a high rate of parasite infection and a control area, and biomarkers were analysed in the liver, gills and epithelial mucosa. Both salinity and the parasite induced increases in catalase (CAT) and glutathione s-transferase activities in the liver, while superoxide dismutase (SOD) did not show significant changes. The effects of salinity were evident to a greater extent in the gills with an increase in the activity of all enzymes, as well as in the production of reactive species. The effects of the parasite were mainly observed in the mucus with significant increases in CAT and SOD activities. Regarding immune response markers in the mucus, both stressors induced an increase in lysozyme and alkaline phosphatase activities, and in the case of the parasite, also an increase in immunoglobulins. Malondialdehyde, as an indicator of oxidative damage, remained unchanged. In conclusion, both abiotic and abiotic stress induce a stress situation in C. julis that responds by activating its antioxidant and immune defence mechanisms but does cause oxidative damage. The differential tissue response to different stressors highlights the value of analysing multiple tissues to detect early indicators of diverse impacts on marine fauna.

IL-10 and IL-18: Key players in liver damage associated with hepatitis A virus infection.

Hepatitis A virus infection is a health threat with multiple transmission patterns across areas, It is evaluated using immune response markers IL-10 and IL-18, along with molecular and biochemical diagnostic methods for accurate diagnosis. The association between liver damage and interleukin-10 and interleukin-18 levels in people with hepatitis A virus infection as indications of the risk of acute liver failure. 110 samples were collected from Iraqi individuals from both sexes and different age groups ⩽ 1 to ⩾ 25, including 60 patients and 50 healthy people. All samples were collected from a hospital in Diwaniyah city, and the infection was confirmed by antiHAV IgM titers and One-Step RT-PCR. ELISA was used to determine the levels of IL-10 and IL-18, while Biochemical tests measured for alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total serum Bilirubin (TSB) in serum. In this study, IL-10 levels were higher in HAV patients (0.12 ± 0.06 ng/L) compared to controls (0.11 ± 0.04 ng/L), but the difference was not significant (p= 0.17). Conversely, IL-18 levels were significantly elevated in patients (1.41 ± 0.71) versus controls (0.58 ± 0.35) (p= 0.00). Biochemical tests showed significantly elevated levels in HAV patients: ALT (170.18 ± 117.67 vs. 21.25 ± 7.41), AST (183.05 ± 128.13 vs. 26.00 ± 7.69), ALP (607.68 ± 214.93 vs. 202.02 ± 121.35), and TSB (2.77 ± 2.5 vs. 0.55 ± 0.14) (all p< 0.001). These findings underscore the potential of IL-10 and IL-18 as biomarkers for HAV severity and highlight their role in liver injury. Our study highlights the important roles of IL-10 and IL-18 in acute hepatitis A and reveals their impact on the immune response and liver damage. Elevated levels of IL-10, IL-18 and Biochemical tests are associated with disease severity, suggesting their potential as biomarkers and therapeutic targets to improve the management of HAV infection.

РОЛЬ ИММУННОГО ОТВЕТА В РАЗВИТИИ ГИПОКСИЧЕСКИХ ОСЛОЖНЕНИЙ РЕСПИРАТОРНЫХ ИНФЕКЦИЙ НИЖНИХ ДЫХАТЕЛЬНЫХ ПУТЕЙ У ДЕТЕЙ

Pneumonia is one of the most common severe infectious diseases in pediatric practice. Hypoxia is common in children with pneumonia and is one of the main predictors of poor outcome. The role of the central link in the cellular response to hypoxia is played by the family of hypoxia-inducible factors (HIF). HIF-1α is the key regulator of both T- and B-lymphocyte functions. The processes of their maturation are accompanied by the formation of circular DNA fragments, TREC (T-cell Receptor Excision Circle) and KREC (Kappa-deleting Recombination Excision Circle). TREC and KREC are unable to replicate and serve as markers for naive lymphocyte production. In its turn, HIF-1α can be used as a marker for cellular hypoxia. The use of TREC and KREC in assessing the immune system in patients with various immunological and infectious pathologies has already been described. At the same time, HIF-1α has so far been little studied as yet. The purpose of this research was to analyze the scientific bibliographical data on the HIF-1α assessment as a marker for hypoxia as well as the quantitative level of TREC and KREC as markers for the adaptive immune response; to study the bibliographical sources on the effect of hypoxia on the immune response, including as part of lower respiratory tract infections. Methods used: bibliographical research in Scopus, PubMed and Google Scholar with keywords “TREC,” “KREC,” “HIF,” “hypoxia,” “pneumonia,” “immune response,” that was then followed by the search results’ systematization, analysis and synthesis. Results: the analysis of bibliographical sources had allowed the Authors to conclude that there is a possible close connection between acute hypoxia and the formation of an adequate immune response in infectious pathologies. Research in this area is still extremely scarce. At the same time, the prospects for this area determine the need for further fundamental and clinical research. Conclusion: it is of a great scientific and clinical interest to be able to non-invasively assess the degree of acute hypoxia during an ongoing infectious disease by examining urinary HIF-1α levels. Particularly promising is the assessment of the HIF-1α level not only as a regulator of tissue adaptation to acute hypoxia, but also as a modulator of the immune response. Taking into consideration the analyzed data, both TREC and KREC appear to be the optimal markers characterizing the functional state of the adaptive immune system.

Non-Thermal Effects of Terahertz Radiation on Gene Expression: Systematic Review and Meta-Analysis.

With the advancement of terahertz technology, unveiling the mysteries of terahertz has had a profound impact on the field of biomedicine. However, the lack of systematic comparisons for gene expression signatures may diminish the effectiveness and efficiency of identifying common mechanisms underlying terahertz effects across diverse research findings. We performed a comprehensive review and meta-analysis to compile patterns of gene expression profiles associated with THz radiation. Thorough bibliographic reviews were conducted, utilizing the PubMed, Embase, Web of Science, and ProQuest databases to extract references from published articles. Raw CEL files were obtained from Gene Expression Omnibus and preprocessed using Bioconductor packages. This systematic review (Registration No. CDR42024502937) resulted in a detailed analysis of 13 studies (14 papers). There are several possible mechanisms and pathways through which THz radiation could cause biological changes. While the established gene expression results are largely associated with immune response and inflammatory markers, other genes demonstrated transcriptional outcomes that may unravel unknown functions. The enrichment of genes primarily found networks associated with broader stress responses. Altogether, the findings showed that THz can induce a distinct transcriptomic profile that is not associated with a microthermal cellular response. However, it is impossible to pinpoint a single gene or family of genes that would accurately and reliably justify the patterns of gene expression response under THz exposure.

Mass cytometric single cell immune profiles of peripheral blood from acute myeloid leukemia patients in complete remission with measurable residual disease.

Measurable residual disease (MRD) is detected in approximately a quarter of AML chemotherapy responders, serving as a predictor for relapse and shorter survival. Immunological control of residual disease is suggested to prevent relapse, but the mechanisms involved are not fully understood. We present a peripheral blood single cell immune profiling by mass cytometry using a 42-antibody panel with particular emphasis on markers of cellular immune response. Six healthy donors were compared with four AML patients with MRD (MRD+) in first complete remission (CR1MRD+). Three of four patients demonstrated a favorable genetic risk profile, while the fourth patient had an unfavorable risk profile (complex karyotype, TP53-mutation) and a high level of MRD. Unsupervised clustering using self-organizing maps and dimensional reduction analysis was performed for visualization and analysis of immune cell subsets. CD57+ natural killer (NK)-cell subsets were found to be less abundant in patients than in healthy donors. Both T and NK cells demonstrated elevated expression of activity and maturation markers (CD44, granzyme B, and phosho-STAT5 Y694) in patients. Although mass cytometry remains an expensive method with limited scalability, our data suggest the utility for employing a 42-plex profiling for cellular immune surveillance in whole blood, and possibly as a biomarker platform in future clinical trials. The findings encourage further investigations of single cell immune profiling in CR1MRD+ AML-patients.

Overview of Hepatitis B Vaccine Non-Response and Associated B Cell Amnesia: A Scoping Review.

The advent of the hepatitis B vaccine has achieved tremendous success in eradicating and reducing the burden of hepatitis B infection, which is the main culprit for hepatocellular carcinoma-one of the most fatal malignancies globally. Response to the vaccine is achieved in about 90-95% of healthy individuals and up to only 50% in immunocompromised patients. This review aimed to provide an overview of hepatitis B vaccine non-response, the mechanisms involved, B cell amnesia, and strategies to overcome it. Databases, including Google Scholar, PubMed, Scopus, Cochrane, and ClinicalTrials.org, were used to search and retrieve articles using keywords on hepatitis B vaccine non-response and B cell amnesia. The PRISMA guideline was followed in identifying studies, screening, selection, and reporting of findings. A total of 133 studies on hepatitis B vaccine non-response, mechanisms, and prevention/management strategies were included in the review after screening and final selection. Factors responsible for hepatitis B vaccine non-response were found to include genetic, immunological factors, and B cell amnesia in healthy individuals. The genetic factors were sex, HLA haplotypes, and genetic polymorphisms in immune response markers (cytokines). Non-response was common in conditions of immunodeficiency, such as renal failure, haemodialysis, celiac disease, inflammatory bowel disease, hepatitis C co-infection, and latent hepatitis B infection. Others included diabetes mellitus and HIV infection. The mechanisms involved were impaired immune response by suppression of response (T helper cells) or induced suppression of response (through regulatory B and T cells). A comprehensive and careful understanding of the patient factors and the nature of the vaccine contributes to developing effective preventive measures. These include revaccination or booster dose, vaccine administration through the intradermal route, and the use of adjuvants in the vaccine.

Identification of a novel cellular senescence-related lncRNA signature for prognosis and immune response in osteosarcoma.

Cellular senescence, a novel hallmark of cancer, is associated with patient outcomes and tumor immunotherapy. However, at present, there is no systematic study on the use of cellular senescence-related long non-coding RNAs (CSR-lncRNAs) to predict survival in patients with osteosarcoma. In this study, we aimed to identify a CSR-lncRNAs signature and to evaluate its potential use as a survival prognostic marker and predictive tool for immune response of osteosarcoma. We downloaded a cohort of patients with osteosarcoma from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We performed differential expression and co-expression analyses to identify CSR-lncRNAs. We performed univariate and multivariate Cox regression analyses along with the random forest algorithm to identify lncRNAs significantly correlated with senescence. Subsequently, we assessed the predictive models using survival curves, receiver operating characteristic curves, nomograms, C-index, and decision curve analysis. Based on this model, patients with osteosarcoma were divided into two groups according to their risk scores. Then, using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, we compared their clinical characteristics to uncover functional differences. We further conducted immune infiltration analyses using estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE), cell-type identification by estimating relative subsets of rna transcripts (CIBERSORT), and single-sample gene set enrichment analysis for the two groups. We also evaluated the expression of the target genes of immune checkpoint inhibitors (ICIs). We identified six lncRNAs that were significantly correlated with senescence and accordingly established a novel cellular senescence-related lncRNA prognostic signature incorporating these lncRNAs. The nomogram indicated that the risk model was an independent prognostic factor that could predict the survival of patients with osteosarcoma. This model demonstrated high accuracy upon validation. Further analysis revealed that patients with osteosarcoma in the low-risk group exhibited better clinical outcomes and enhanced immune infiltration. The six-CSR-lncRNA prognostic signature effectively predicted survival outcomes and patients in the low-risk group might have improved immune infiltration.

Seroprevalence, Risk Factors and Immunological Response against Hepatitis B Virus Among Students of Usmanu Danfodiyo University Sokoto, Nigeria

Study’s Excerpt The seroprevalence of Hepatitis B Virus (HBV) among university students was investigated. Both serological markers of HBV and immune response were assessed. The results revealed significant associations between infection and high-risk behaviors. Full Abstract Hepatitis B Virus is of major public health interest as it accounts for significant mortality globally. The study aimed to determine the seroprevalence of HBV infection, the possible potential risk factors, and the immunological response among students of Usmanu Danfodiyo University, Sokoto, from December 2022 to April 2023. Structured questionnaires were used to collect sociodemographic information as well as possible risk factors related to the infection. Out of 139 study participants (10 females and 129 males screened randomly for HBsAg using a rapid HBsAg test kit, 17 (12.2%) were seropositive, and 122 (87.8%) were seronegative. The sera of the positive participants were further screened for HBeAg, anti-(HBs, HBe, and HBc) using one-step cassette diagnostic kits. Of the 17 positive samples screened, none were reactive for anti-HBs antibodies and HBeAg.; while 15 were positive anti-HBc and anti-HBe, indicating a response to natural infection. Sexual activity, unprotected sexual practices, use of already used sharp objects, and awareness of HBV infection were significantly associated (P&lt;0.05) with the viral infection. The study indicates high endemicity in the study area. It is recommended that Nigerian Universities mandate the Hepatitis B virus vaccine for newly intake students. More awareness should be created about the dangers of unprotected sexual practice use or sharing of used sharp objects, among other possible factors.

Anti-Inflammatory Interventions for Autism Spectrum Disorder

One of the defining factors of Autism Spectrum Disorder (ASD) is neuroinflammation, which may be targeted to find effective therapies in managing ASD symptoms. Some promising treatments include mesenchymal STEM cell (MSCs) therapy, cxytocin (OT), sulforaphane (SFN), and resveratrol (RSV). MSCs are located in many parts of the body that can reduce secondary neurodegeneration and neuroinflammation while promoting neurogenesis and angiogenesis. OT is a hormone that moderates social and emotional communication, bonding, and social learning, while also having profound antiinflammatory effects. SFN is a naturally occurring compound in cruciferous vegetables, such as broccoli and sprouts, and activates a transcription factor which regulates anti-inflammatory and antioxidant genes. RSV is found in plants, such as grapes and berries, and helps stabilize the central and peripheral immune response and oxidative stress markers, subsequently reducing neuroinflammation. All of these treatments have shown promising potential, but it is abundantly clear that further research is needed in addition to combined therapies. Since ASD is a spectrum, not every case can be treated the exact same way. By targeting neuroinflammation, we can address the root cause of ASD rather than the symptoms.

Single-cell Transcriptional Landscape of Temporal Neutrophil Response to Burn Wound in Larval Zebrafish.

Neutrophils accumulate early in tissue injury. However, the cellular and functional heterogeneity of neutrophils during homeostasis and in response to tissue damage remains unclear. In this study, we use larval zebrafish to understand neutrophil responses to thermal injury. Single-cell transcriptional mapping of myeloid cells during a 3-d time course in burn and control larvae revealed distinct neutrophil subsets and their cell-cell interactions with macrophages across time and conditions. The trajectory formed by three zebrafish neutrophil subsets resembles human neutrophil maturation, with varying transition patterns between conditions. Through ligand-receptor cell-cell interaction analysis, we found that neutrophils communicate more in burns in a pathway and temporal manner. Finally, we identified the correlation between zebrafish myeloid signatures and human burn severity, establishing GPR84+ neutrophils as a potential marker of early innate immune response in burns. This work builds a comparative single-cell transcriptomic framework to identify neutrophil markers of tissue damage using model organisms.