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This research was conducted to examine the impact of Wei Qi Booster (WQB) on immune parameters and anti-oxidative function in aged mice. Fifty aged mice were randomly assigned to five different groups. Group A was designated as the control group. Mice in Group B were receiving Levamisole at 10  mg/kg body weight. Each mouse in groups C, D and E received 0.1, 1, and 2% WQB, respectively. Another ten young mice, designated as group F, were fed regularly. The mice were fed according to the above methods for 28  days. Results showed that relative to the control group, the body weight and immune organs indexes experienced a substantial rise in the group with 1% WQB. In addition, 1% WQB could improve the activity of SOD and reduce the MDA levels. Expressions of CD4 and sIgA increased while CD8 decreased in the jejunum of aged mice treated with WQB. IL2 and IFN-γ levels increased in the 1% WQB group, showing no notable difference compared to the young mice group. The results demonstrated that WQB can elevate immune levels and enhance anti-oxidative functions in aged mice. [ABSTRACT FROM AUTHOR]

Recent research has extensively explored the intricate mechanisms that underlie the effectiveness of acupuncture, highlighting the importance of stimulating acupoints, the role of acupuncture techniques in managing diseases, and the interaction between meridian pathways and molecular processes. Studies have underscored the crucial role of acupuncture in activating neurons, modulating the immune system, and influencing vascular activity, all of which contribute significantly to its therapeutic benefits across a wide range of symptoms and conditions. Utilization of imaging modalities enables the identification of changes in cerebral blood flow, brain function, and regional glucose metabolism following acupuncture sessions. The interstitial fluid circulation network within meridians adheres to specific laws that facilitate the transportation of materials. Acupuncture initiates the release of neurotransmitters, neuropeptides, and immune factors, impacting pain perception, inflammation, and physiological functions. It influences the complex neuro–endocrine–immune network by activating pathways involving the nervous system, the hypothalamic-pituitary-adrenal axis, and immune responses. Moreover, acupuncture induces molecular modifications such as phosphorylation, methylation, and histone modification, leading to key molecular changes that ultimately result in anti-inflammatory effects and the regulation of immune responses. [ABSTRACT FROM AUTHOR]

PRF1 (perforin 1) is a key cytotoxic molecule that plays a crucial role in the killing function of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Recent studies have focused on PRF1's role in cancer development, progression, and prognosis. Studies have shown that aberrant PRF1 expression has a significant role to play in cancer development and progression. In some cancers, high expression of the PRF1 gene is associated with a better prognosis for patients, possibly because it helps enhance the body's immune response to tumors. However, some studies have also shown that the absence of PRF1 may make it easier for tumors to evade the body's immune surveillance, thus affecting patient survival. Furthermore, recent studies have explored therapeutic strategies based on PRF1, such as enhancing the ability of immune cells to kill cancer cells by boosting PRF1 activity. In addition, they have improved the efficacy of immunotherapy by modulating its expression to enhance the effectiveness of the treatment. Based on these findings, PRF1 may be a valuable biomarker both for the treatment of cancer and for its prognosis in the future. To conclude, PRF1 has an important biological function and has clinical potential for the treatment of cancer, which indicates that it deserves more research and development in the future. [ABSTRACT FROM AUTHOR]

SLAMF9, a member of the conserved lymphocyte activation molecules family (SLAMF), has been less investigated compared to other SLAMs, especially concerning its implications across various cancer types. In our systematic pan-cancer investigation, we observed elevated SLAMF9 expression in various tumor tissues, which was correlated with reduced patient survival across most malignancies. Correlation analyses further revealed significant associations between SLAMF9 expression and immune cell infiltrates, immune checkpoint inhibitors, tumor mutation load, microsatellite instability, and epithelial–mesenchymal transition (EMT) scores. Cell-based assays demonstrated that SLAMF9 knockdown attenuated the proliferative, motile, and invasive capacities of colorectal cancer (CRC) cells. In a nude mouse xenograft model, suppression of SLAMF9 expression substantially inhibited tumor growth. These findings highlight the potential of SLAMF9 as a prognostic and therapeutic biomarker across tumors, with notable implications for CRC cell proliferation and migration. [ABSTRACT FROM AUTHOR]

The gut‐immune axis is a relatively novel phenomenon that provides mechanistic links between the gut microbiome and the immune system. A growing body of evidence supports it is key in how the gut microbiome contributes to several diseases, including hypertension and cardiovascular diseases (CVDs). Evidence over the past decade supports a causal link of the gut microbiome in hypertension and its complications, including myocardial infarction, atherosclerosis, heart failure, and stroke. Perturbations in gut homeostasis such as dysbiosis (i.e., alterations in gut microbial composition) may trigger immune responses that lead to chronic low‐grade inflammation and, ultimately, the development and progression of these conditions. This is unsurprising, as the gut harbors one of the largest numbers of immune cells in the body, yet is a phenomenon not entirely understood in the context of cardiometabolic disorders. In this review, we discuss the role of the gut microbiome, the immune system, and inflammation in the context of hypertension and CVD, and consolidate current evidence of this complex interplay, whilst highlighting gaps in the literature. We focus on diet as one of the major modulators of the gut microbiota, and explain key microbial‐derived metabolites (e.g., short‐chain fatty acids, trimethylamine N‐oxide) as potential mediators of the communication between the gut and peripheral organs such as the heart, arteries, kidneys, and the brain via the immune system. Finally, we explore the dual role of both the gut microbiome and the immune system, and how they work together to not only contribute, but also mitigate hypertension and CVD. [ABSTRACT FROM AUTHOR]

Despite the progress made in the management of lung adenocarcinoma (LUAD), the overall prognosis for LUAD individuals remains suboptimal. While the role of cell polarity in tumor invasion and metastasis is well established, its prognostic significance in LUAD is still unknown. Differential analysis was performed on the Cancer Genome Atlas (TCGA)‐LUAD and normal lung tissue, and candidate genes were identified by intersecting differentially expressed genes with polarity‐related genes (PRGs). A prognostic model was constructed using univariate and multivariate Cox regression and LASSO regression. To enhance the robustness of the analysis, an independent prognostic analysis was conducted by incorporating relevant clinical information. The accuracy and sensitivity of the model were validated using survival analysis and ROC curves. Finally, immune landscape, immune therapy, tumor mutation burden, and drug sensitivity analysis were carried out on high‐ and low‐risk patients. Ten prognostic genes were screened to divide LUAD patients into different risk groups. Survival analysis, ROC curves, and univariate/multivariate Cox regression analyses collectively demonstrated the favorable predictive performance of the model, which could be an independent prognostic factor. The nomogram, in conjunction with the calibration curve, demonstrated the model's compelling predictive capacity in prognosticating the overall survival of LUAD individuals. Low‐risk LUAD patients exhibited heightened levels of immune cell infiltration, immune scores, and immune checkpoint expression compared to high‐risk individuals. So, they may have a greater likelihood of benefiting from immune therapy. The high‐risk group demonstrated a remarkably higher tumor mutation burden (TMB) in contrast with the low‐risk group. XAV‐939, Fulvestrant, and SR16157 may have potential value in the clinical use of LUAD. We revealed the potential linkage between PRGs and LUAD prognosis, and the application of these prognostic factors in risk stratification and prognosis prediction of LUAD patients may be of great significance. [ABSTRACT FROM AUTHOR]

• Anxiety in pregnancy is associated with immune dysregulation. • We measured longitudinal change in antenatal immune activity in a Pakistani population. • High anxiety was associated with increased chemokine activity across pregnancy. • Higher chemokine activity predicted low birthweight and small for gestational age. Dysregulation of the immune system has been associated with psychiatric disorders and pregnancy-related complications, such as perinatal depression. However, the immune characteristics specific to perinatal anxiety remain poorly understood. In this study, our goal was to examine specific immune characteristics related to prenatal anxiety within the context of a randomized controlled trial designed to alleviate anxiety symptoms—the Happy Mother − Healthy Baby (HMHB) study in Rawalpindi, Pakistan. Pregnant women (n = 117) were followed prospectively in the 1st, 2nd, and 3rd trimesters (T1, T2, T3) and at 6 weeks postpartum (PP6). Each visit included a blood draw and anxiety evaluation (as measured by the anxiety subscale of the Hospital Anxiety and Depression Scale – HADS –using a cutoff ≥ 8). We enrolled both healthy controls and participants with anxiety alone; those with concurrent depression were excluded. K-means cluster analysis revealed three anxiety clusters: Non-Anxiety, High and Consistent Anxiety, and Decreasing Anxiety. Principal components analysis revealed two distinct clusters of cytokine and chemokine activity. Women within the High and Consistent Anxiety group had significantly elevated chemokine activity across pregnancy (in trimester 1 (β = 0.364, SE = 0.178, t = 2.040, p = 0.043), in trimester 2 (β = 0.332, SE = 0.164, t = 2.020, p = 0.045), and trimester 3 (β = 0.370, SE = 0.179, t = 2.070, p = 0.040) compared to Non-Anxiety group. Elevated chemokine activity was associated with low birthweight (LBW) and small for gestational age (SGA). Our findings reveal a unique pattern of immune dysregulation in pregnant women with anxiety in a Pakistani population and offer preliminary evidence that immune dysregulation associated with antenatal anxiety may be associated with birth outcomes. The dysregulation in this population is distinct from that in our other studies, indicating that population-level factors other than anxiety may play a substantial role in the differences found. (Clinicaltrials.gov # NCT04566861) [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to stratify preoperative immune cell counts by cancer specific outcomes in patients with renal cell carcinoma (RCC) and a tumor thrombus after radical nephrectomy with tumor thrombectomy. Methods: Patients with a diagnosis of RCC with tumor thrombus that underwent radical nephrectomy with thrombectomy across an international consortium of seven institutions were included. Patients who were metastatic at diagnosis and those who received preoperative medical treatment were also included. Retrospective chart review was performed to collect demographic information, past medical history, preoperative lab work, surgical pathology, and follow up data. Neutrophil counts, lymphocyte counts, monocyte counts, neutrophil to lymphocyte ratios (NLR), lymphocyte to monocyte ratios (LMR), and neutrophil to monocyte ratios (NMR) were compared against cancer-specific outcomes using independent samples t -test, Pearson's bivariate correlation, and analysis of variance. Results: One hundred forty-four patients were included in the study, including nine patients who were metastatic at the time of surgery. Absolute lymphocyte count preoperatively was greater in patients who died from RCC compared to those who did not (2 vs 1.4; p < 0.001). Patients with tumor pathology showing perirenal fat invasion had a greater neutrophil count compared to those who did not (7.5 vs 5.5; p = 0.010). Patients with metastatic RCC had a lower LMR compared to those without metastases after surgery (2.5 vs 3.2; p = 0.041). Tumor size, both preoperatively and on gross specimen, had an interaction with multiple immune cell metrics (p < 0.05). Conclusions: Preoperative immune metrics have clinical utility in predicting cancer-specific outcomes for patients with RCC and a tumor thrombus. Additional study is needed to determine the added value of preoperative serum immune cell data to established prognostic risk calculators for this patient population. [ABSTRACT FROM AUTHOR]

Immune cells in the human lung are associated with idiopathic pulmonary fibrosis. However, the contribution of different immune cell subpopulations to the pathogenesis of pulmonary fibrosis remains unclear. We used single-cell RNA sequencing data to investigate the transcriptional profiles of immune cells in the lungs of 5 IPF patients and 3 subjects with non-fibrotic lungs. In an identifiable population of immune cells, we found increased percentage of CD8+ T cells in the T cell subpopulation in IPF. Monocle analyzed the dynamic immune status and cell transformation of CD8+ T cells, as well as the cytotoxicity and exhausted status of CD8+ T cell subpopulations at different stages. Among CD8+ T cells, we found differences in metabolic pathways in IPF and Ctrl, including lipid, amino acid and carbohydrate metabolic. By analyzing the metabolites of CD8+ T cells, we found that different populations of CD8+ T cells in IPF have unique metabolic characteristics, but they also have multiple identical up-regulated or down-regulated metabolites. In IPF, signaling pathways associated with fibrosis were enriched in CD8+ T cells, suggesting that CD8+ T cells may have an important contribution to fibrosis. Finally, we analyzed the interactions between CD8+ T cells and other cells. Together, these studies highlight key features of CD8+ T cells in the pathogenesis of IPF and help to develop effective therapeutic targets. • The percentage of CD8+ T cells in the T cell subpopulation increased in IPF patients. • In CD8+ T cells, we found differences in the metabolic pathways of IPF and Ctrl. • Different populations of CD8+ T cells in IPF have unique metabolic characteristics. • Signaling pathways associated with fibrosis are enriched in CD8+ T cells in IPF patients. [ABSTRACT FROM AUTHOR]

Infections during pregnancy are associated with increased risk for adult neuropsychiatric disease, such as major depressive disorder, schizophrenia, and autism spectrum disorder. In mouse models of maternal immune activation (MIA), different toll‐like receptors (TLRs) are stimulated to initiate inflammatory responses in mother and fetus. The goal of this study was to determine sex‐dependent aspects of MIA using a TLR7/8 agonist, Resiquimod (RQ), on neurodevelopment. RQ was administered to timed‐pregnant mice on embryonic day (E) 12.5. At E15, maternal/fetal plasma cytokines were measured by enzyme‐linked immunosorbent assay (ELISA). Maternal cytokines interleukin (IL)‐6 and IL‐10 were higher while tumor necrosis factor (TNF)‐α and IL‐17 were lower in pregnant dams exposed to RQ. Fetal cytokines (E15) were altered at the same timepoint with fetal plasma IL‐6 and IL‐17 greater after RQ compared to vehicle, while IL‐10 and TNF‐α were higher in male fetuses but not female. Other timed‐pregnant dams were allowed to give birth. MIA with RQ did not alter the female to male ratio of offspring born per litter. Body weights were reduced significantly in both sexes at birth, and over the next 5 weeks. Offspring from RQ‐injected mothers opened their eyes 5 days later than controls. Similarly, female offspring from RQ‐injected mothers exhibited pubertal delay based on vaginal opening 2–3 days later than control females. On the behavioral side, juvenile and adult male and female MIA offspring exhibited less social‐like behavior in a social interaction test. Anhedonia‐like behavior was greater in MIA adult female mice. This study provides support for sex‐dependent influences of fetal antecedents for altered brain development and behavioral outputs that could be indicative of increased susceptibility for adult disorders through immune mechanisms. Future studies are needed to determine neural cellular and molecular mechanisms for such programming effects. [ABSTRACT FROM AUTHOR]

Background: Palatal expansion is a common way of treating maxillary transverse deficiency. Under mechanical force, the midpalatal suture is expanded, causing local immune responses. This study aimed to determine whether macrophages participate in bone remodeling of the midpalatal suture during palatal expansion and the effects on bone remodeling. Methods: Palatal expansion model and macrophage depletion model were established. Micro-CT, histological staining, and immunohistochemical staining were used to investigate the changes in the number and phenotype of macrophages during palatal expansion as well as the effects on bone remodeling of the midpalatal suture. Additionally, the effect of mechanically induced M2 macrophages on palatal osteoblasts was also elucidated in vitro. Results: The number of macrophages increased significantly and polarized toward M2 phenotype with the increase of the expansion time, which was consistent with the trend of bone remodeling. After macrophage depletion, the function of osteoblasts and bone formation at the midpalatal suture were impaired during palatal expansion. In vitro, conditioned medium derived from M2 macrophages facilitated osteogenic differentiation of osteoblasts and decreased the RANKL/OPG ratio. Conclusions: Macrophages through polarizing toward M2 phenotype participated in midpalatal suture bone remodeling during palatal expansion, which may provide a new idea for promoting bone remodeling from the perspective of regulating macrophage polarization. [ABSTRACT FROM AUTHOR]

Purpose of Review: Huntington's disease (HD) is an autosomal-dominant disorder caused by a pathological expansion of a trinucleotide repeat (CAG) on exon 1 of the huntingtin (HTT) gene. HD is characterized by the presence of chorea, alongside other hyperkinesia, parkinsonism and a combination of cognitive and behavioural features. Currently, there are no disease-modifying therapies (DMTs) for HD, and the only intervention(s) with approved indication target the treatment of chorea. This article reviews recent research on the clinical development of DMTs and newly developed tools that enhance clinical trial design towards a successful DMT in the future. Recent Findings: HD is living in an era of target-specific drug development with emphasis on the mechanisms related to mutant Huntingtin (HTT) protein. Examples include antisense oligonucleotides (ASO), splicing modifiers and microRNA molecules that aim to reduce the levels of mutant HTT protein. After initial negative results with ASO molecules Tominersen and WVE-120101/ WVE-120102, the therapeutic landscape continues to expand, with various trials currently under development to document proof-of-concept and safety/tolerability. Immune-targeted therapies have also been evaluated in early-phase clinical trials, with promising preliminary findings. The possibility of quantifying mHTT in CSF, along with the development of an integrated biological staging system in HD are important innovations applicable to clinical trial design that enhance the drug development process. Summary: Although a future in HD with DMTs remains a hope for those living with HD, care partners and care providers, the therapeutic landscape is promising, with various drug development programs underway following a targeted approach supported by disease-specific biomarkers and staging frameworks. [ABSTRACT FROM AUTHOR]

Ultrasound has expanded into the therapeutic field as a medical imaging and diagnostic technique. Low-intensity pulsed ultrasound (LIPUS) is a kind of therapeutic ultrasound that plays a vital role in promoting fracture healing, wound repair, immunomodulation, and reducing inflammation. Its anti-inflammatory effects are manifested by decreased pro-inflammatory cytokines and chemokines, accelerated regression of immune cell invasion, and accelerated damage repair. Although the anti-inflammatory mechanism of LIPUS is not very clear, many in vitro and in vivo studies have shown that LIPUS may play its anti-inflammatory role by activating signaling pathways such as integrin/Focal adhesion kinase (FAK)/Phosphatidylinositol 3-kinase (PI3K)/Serine threonine kinase (Akt), Vascular endothelial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS), or inhibiting signaling pathways such as Toll-like receptors (TLRs)/Nuclear factor kappa-B (NF-κB) and p38-Mitogen-activated protein kinase (MAPK). As a non-invasive physical therapy, the anti-inflammatory and immunomodulatory effects of LIPUS deserve further exploration. [ABSTRACT FROM AUTHOR]

This study aimed to determine the effects of different doses of Acremonium terricola culture (ATC) on lactation performance, immune function, antioxidant capacity, and intestinal flora of sows. Forty-five Landrace sows (3–6 parity) were randomly assigned to the following three treatments from 85 days of gestation to 21 days after farrowing: a control diet (CON, basal diet), a low-dose Acremonium terricola culture diet (0.2% ATC, basal diet + 0.2% ATC), and a high-dose Acremonium terricola culture diet (0.4% ATC, basal diet + 0.4% ATC). Compared with the CON group, the supplementation of 0.2% ATC increased the average daily milk yield of sows by 4.98%, increased milk fat, total solids, and freezing point depression on day 1 postpartum (p < 0.05), increased serum concentration of Triiodothyronine, Thyroxin, and Estradiol on day 21 postpartum (p < 0.05). Compared with the CON group, the supplementation of 0.4% ATC increased the average daily milk yield of sows by 9.38% (p < 0.05). Furthermore, the supplementation of 0.2% ATC increased serum concentration of IgG, IgM, and IFN-γ, CD4 on day 1 postpartum (p < 0.05) and increased serum concentration of immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), complement 3 (C3), cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8), interferon-γ (IFN-γ) on day 21 postpartum (p < 0.05), while the supplementation of 0.4% ATC reduced serum concentration of IL-2 on day 21 postpartum (p < 0.05). Moreover, the supplementation of 0.4% ATC significantly increased serum concentration of catalase (CAT) (p < 0.05). Additionally, the supplementation of ATC affected the relative abundance of the intestinal flora at different taxonomic levels in sows and increased the abundance of beneficial bacteria such as in the norank_f__Eubacterium_coprostanoligenes group, Eubacterium_coprostanoligenes group, and Lachnospiraceae_XPB1014 group of sows, while reducing the abundance of harmful bacteria such as Phascolarctobacterium and Clostridium_sensu_stricto_1. These data revealed that the supplementation of ATC during late gestation and lactation can improve lactation performance, immune function, antioxidant capacity, and the gut microbiota. Compared with supplementation of 0.4% ATC, 0.2% ATC enhances the levels of thyroid-related hormones, specific antibodies, and cytokines in serum, promotes the diversity of beneficial gut microbiota, beneficial bacteria in the intestine, reduces the population of harmful bacteria, and thereby bolsters the immunity of sows. Hence, 0.2% ATC is deemed a more optimal concentration. [ABSTRACT FROM AUTHOR]

Aims: Atrial fibrillation (AF) is the most common arrhythmia. Heart failure (HF) is a disease caused by heart dysfunction. The prevalence of AF and HF were progressively increasing over time. The co‐existence of AF and HF presents a significant therapeutic challenge. In order to provide new ideas for the diagnosis of AF and HF, it is necessary to carry out biomarker related studies. Methods and results: The training set and validation set data of AF and HF patient samples were downloaded from the GEO database, 'limma' was used to compare the differences in gene expression levels between the disease group and the normal group to screen for differentially expressed genes (DEGs). Weighted correlation network analysis (WGCNA) identified the modules with the highest positive correlation with AF and HF. Functional enrichment and PPI network construction of key genes were carried out. Biomarkers were screened by machine learning. The infiltration of immune cells in AF and HF groups was evaluated by R‐packet 'CIBERSORT'. The miRNA network was constructed and potential therapeutic agents for biomarker genes were predicted through the drugbank database. Through WGCNA analysis, it was found that the modules most positively correlated with AF and HF were MEturquoise (r = 0.21, P value = 0.09) and MEbrown (r = 0.62, P value = 8e‐12), respectively. We screened 25 genes that were highly correlated with both AF and HF. Lasso regression analysis results showed 7 and 20 core genes in AF and HF groups, respectively. The top 20 important genes in AF and HF groups were obtained as core genes by RF model analysis. Four biomarkers were obtained after the intersection of core genes in four groups, namely, GLUL, NCF2, S100A12, and SRGN. The diagnostic efficacy of four genes in AF validation sets was good (AUC: GLUL 0.76, NCF2 0.64, S100A12 0.68, and SRGN 0.76), as well as in the HF validation set (AUC: GLUL 0.76, NCF2 0.84, S100A12 0.92, and SRGN 0.68). The highest correlation with neutrophils was observed for GLUL, NCF2, and S100A12, while SRGN exhibited the strongest correlation with T cells CD4 memory resting in the AF group. GLUL, NCF2, S100A12, and SRGN were most associated with neutrophils in the HF group. A total of 101 miRNAs were predicted by four genes, and GLUL, NCF2, and S100A12 predicted a total of 10 potential therapeutic agents. Conclusions: We identified four biological markers that are highly correlated with AF and HF, namely, GLUL, NCF2, S100A12, and SRGN. Our findings provide theoretical basis for the clinical diagnosis and treatment of AF and HF. [ABSTRACT FROM AUTHOR]

AbstractHepatocellular carcinoma (HCC), as a malignancy derived from liver tissue, is typically associated with poor prognosis. Increasing evidence suggests a connection between pyrimidine metabolism and HCC progression. The purpose of this study was to establish a model applied to the prediction of HCC patients’ overall survival. Transcriptomic data of HCC patients were downloaded from The Cancer Genome Atlas (TCGA) website. Pyrimidine metabolism-related genes (PMRGs) were collected from the Gene Set Enrichment Analysis (GSEA) website. Differential gene expression analysis was carried out on the HCC data, followed by an intersection of the differentially expressed genes (DEGs) and PMRGs. Subsequently, a prognostic model incorporating nine genes was established using univariate/multivariate Cox regression and Least absolute shrinkage and selection operator (LASSO) regression. Survival analysis demonstrated that the high-risk group defined by this model had considerably shorter overall survival than the low-risk group in both TCGA and Gene Expression Omnibus (GEO) datasets. Receiver operating characteristic (ROC) analysis indicated the good predictive capability of the model. CIBERSORT and single sample gene set enrichment analysis (ssGSEA) algorithms revealed significantly higher levels of Macrophages M0 and lower levels of natural killer (NK)_cells in the high-risk group compared to the low-risk group. The immunophenoscore (IPS) and the tumor immune dysfunction and exclusion (TIDE) score demonstrated that the model could significantly differentiate patients who would be more suitable for immunotherapy. Moreover, the CellMiner database was utilized to predict anti-tumor drugs significantly associated with the model genes. Collectively, the potential prognostic significance of pyrimidine metabolism in HCC was revealed in this study. The prognostic model aids in evaluating the survival time and immune status of HCC patients. [ABSTRACT FROM AUTHOR]

Objective: Disulfidptosis is a newly recognized form of regulated cell death that has been linked to cancer progression and prognosis. Despite this association, the prognostic significance, immunological characteristics and treatment response of disulfidptosis-related lncRNAs (DRLs) in ovarian cancer have not yet been elucidated. Methods: The lncRNA data and clinical information for ovarian cancer and normal samples were obtained from the UCSC XENA. Differential expression analysis and Pearson analysis were utilized to identify core DRLs, followed by LASSO algorithm. Random Survival Forest was used to construct a prognostic model. The relationships between risk scores, RNA methylation, immune cell infiltration, mutation, responses to immunotherapy and drug sensitivity analysis were further examined. Additionally, qRT-PCR experiments were conducted to validate the expression of the core DRLs in human ovarian cancer cells and normal ovarian cells and the scRNA-seq data of the core DRLs were obtained from the GEO dataset, available in the TISCH database. Results: A total of 8 core DRLs were obtained to construct a prognostic model for ovarian cancer, categorizing all patients into low-risk and high-risk groups using an optimal cutoff value. The AUC values for 1-year, 3-year and 5-year OS in the TCGA cohort were 0.785, 0.810 and 0.863 respectively, proving a strong predictive capability of the model. The model revealed the high-risk group patients exhibited lower overall survival rates, higher TIDE scores and lower TMB levels compared to the low-risk group. Variations in immune cell infiltration and responses to therapeutic drugs were observed between the high-risk and low-risk groups. Besides, our study verified the correlations between the DRLs and RNA methylation. Additionally, qRT-PCR experiments and single-cell RNA sequencing data analysis were conducted to confirm the significance of the core DRLs at both cellular and scRNA-seq levels. Conclusion: We constructed a reliable and novel prognostic model with a DRLs cluster for ovarian cancer, providing a foundation for further researches in the management of this disease. [ABSTRACT FROM AUTHOR]

The non-natriuretic-dependent glutamate/cystine inverse transporter-system Xc- is composed of two protein subunits, SLC7A11 and SLC3A2, with SLC7A11 serving as the primary functional component responsible for cystine uptake and glutathione biosynthesis. SLC7A11 is implicated in tumor development through its regulation of redox homeostasis, amino acid metabolism, modulation of immune function, and induction of programmed cell death, among other processes relevant to tumorigenesis. In this paper, we summarize the structure and biological functions of SLC7A11, and discuss its potential role in tumor therapy, which provides a new direction for precision and personalized treatment of tumors. [ABSTRACT FROM AUTHOR]

Spaceflight poses a myriad of environmental stressors to astronauts´ physiology including microgravity and radiation. The individual impacts of microgravity and radiation on the immune system have been extensively investigated, though a comprehensive review on their combined effects on immune system outcomes is missing. Therefore, this review aims at understanding the synergistic, additive, and antagonistic interactions between microgravity and radiation and their impact on immune function as observed during spaceflight-analog studies such as rodent hindlimb unloading and cell culture rotating wall vessel models. These mimic some, but not all, of the physiological changes observed in astronauts during spaceflight and provide valuable information that should be considered when planning future missions. We provide guidelines for the design of further spaceflight-analog studies, incorporating influential factors such as age and sex for rodent models and standardizing the longitudinal evaluation of specific immunological alterations for both rodent and cellular models of spaceflight exposure. [ABSTRACT FROM AUTHOR]

To systematically evaluate the regulatory effects of Yupingfeng polysaccharides on rodents immune function, RevMan3.5 software and Cochrane method was used to analyze. A total of 311 papers were obtained by computerized search of CNKI, VIP, Wanfang, Pubmed, Web of science and Science Direct databases on relevant literature on the effect of yupengfeng polysaccharides on the immunity of rodent, 14 papers were screened according to the inclusion criteria, and Meta-analysis was performed by using the software of RevMan3.5. Lymphocyte proliferation stimulation index (SI), interleukin 2 (IL-2), secretory immunoglobulin A (SIgA), molecular surface-specific marker molecule of helper T cells/cytotoxic lymphocyte molecular surface-specific marker molecule of cytotoxic lymphocytes (CD4+ /CD8+ ), splenic index, and transforming growth factor β1 (TGF-β1). Among them, SI, IL-2, CD4+ /CD8+, spleen index and TGF-β1, showed significant differences compared with the control group (P<0.05), while, SIgA, was not significantly altered (P>0.05) compared with the control group. Sensitivity analyses showed that the analyzed literature had stability and reliability. The publication bias results showed that IL-2 was biased, while CD4+ /CD8+ and spleen index were not. In conclusion, result indicated that Yupingfeng polysaccharide could improve the immune function of rodents to a certain extent, and more studies should be conducted to further verify its immunomodulatory effects. [ABSTRACT FROM AUTHOR]

Background: The current understanding of the mechanisms by which metal ion metabolism promotes the progression and drug resistance of osteosarcoma remains incomplete. This study aims to elucidate the key roles and mechanisms of genes involved in cuproptosis-related sphingolipid metabolism (cuproptosis-SPGs) in regulating the immune landscape, tumor metastasis, and drug resistance in osteosarcoma cells. Methods: This study employed multi-omics approaches to assess the impact of cuproptosis-SPGs on the prognosis of osteosarcoma patients. Lasso regression analysis was utilized to construct a prognostic model, while multivariate regression analysis was applied to identify key core genes and generate risk coefficients for these genes, thereby calculating a risk score for each osteosarcoma patient. Patients were then stratified into high-risk and low-risk groups based on their risk scores. The ESTIMATE and CIBERSORT algorithms were used to analyze the level of immune cell infiltration within these risk groups to construct the immune landscape. Single-cell analysis was conducted to provide a more precise depiction of the expression patterns of cuproptosis-SPGs among immune cell subtypes. Finally, experiments on osteosarcoma cells were performed to validate the role of the cuproptosis-sphingolipid signaling network in regulating cell migration and apoptosis. Results: In this study, seven cuproptosis-SPGs were identified and used to construct a prognostic model for osteosarcoma patients. In addition to predicting survival, the model also demonstrated reliability in forecasting the response to chemotherapy drugs. The results showed that a high cuproptosissphingolipid metabolism score was closely associated with reduced CD8 T cell infiltration and indicated poor prognosis in osteosarcoma patients. Cellular functional assays revealed that cuproptosis-SPGs regulated the LC3B/ERK signaling pathway, thereby triggering cell death and impairing migration capabilities in osteosarcoma cells. Conclusion: The impact of cuproptosis-related sphingolipid metabolism on the survival and migration of osteosarcoma cells, as well as on CD8 T cell infiltration, highlights the potential of targeting copper ion metabolism as a promising strategy for osteosarcoma patients. [ABSTRACT FROM AUTHOR]

Background: The anti-tumor immune reaction has a critical part in the progression together with survival of colorectal cancer (CRC). The expression of T cell-inflamed gene as a potential indicator that predicts the reaction of immunogenic cancer types to checkpoint inhibitor immunotherapy, but its prognostic value in CRC is unclear. Materials and Methods: Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses identified enrichment analysis of T cell-inflamed associated genes. The prognostic model is built and the prognostic genes screened using the LASSO Cox regression model. Relationship among risk score, disease subtypes and immune infiltration was constructed. Besides, risk score was combined with clinicopathological features to further improve prognostic models and survival predictions. Results: We identified 14 T cell-inflamed associated genes were differential expressed in CRC tissues. GO along with KEGG analyses revealed that T cell -inflamed associated genes were implicated in the regulation of immune cells. Through LASSO Cox regression, a 5-gene prognostic model was constructed as well as classified all CRC patients into a low- or high-risk group or different disease subtypes (C1, C2 and C3). In the C3 group the OS rate of CRC patients was longer compared to the C1 group. Additionally, the prognosis Decision Curve Analysis (DCA) map displayed that the risk score was increased compared to the extreme curve and higher than other indicators, showing the strongest survival prediction ability. Conclusion: These results indicated that T cell-inflamed associated gene-based risk score reflected immune microenvironment features as well as predicted prognosis in CRC. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to establish a diagnostic model of endometriosis (EM) based on disulfidptosis‐related genes (DRGs). Materials and Methods: The mRNA expression data of EM were downloaded from the gene expression omnibus database and subjected to differential analysis, and co‐expression analysis was performed based on 10 disulfidptosis genes to acquire DRGs. The differentially expressed DRGs were subjected to biofunctional analysis. Lasso analysis and support vector machine‐recursive feature elimination (SVM‐RFE) analysis were employed to extract the intersection of feature genes as biomarkers, and the diagnostic values of biomarkers for EM were evaluated based on receiver operating characteristic curves. The correlations between biomarkers and the immune microenvironment were assessed by Pearson analysis of biomarkers and immune cell infiltration levels. Results: Transforming growth factor β stimulated protein clone 22 domain family member 4 (TSC22D4), and F‐box/SPRY domain‐containing protein 1 (FBXO45) worked as the diagnostic classifiers in EM, with an obvious decrease in FBXO45 expression and an evident increase in TSC22D4 expression. The areas under the curves of FBXO45 and TSC22D4 were 0.752 and 0.706, respectively, and the area of FBXO45 combined with TSC22D4 reached 0.865, suggesting that TSC22D4 and FBXO45 had high predictive values. The diagnostic markers were closely correlated with immune cell infiltration. Conclusion: The diagnostic markers constructed based on disulfidptosis are good predictors for EM, which have close correlations with EM. [ABSTRACT FROM AUTHOR]

The clinical category of immune-mediated cerebellar ataxias (IMCAs) is now recognized after 3 decades of clinical and experimental research. The cerebellum gathers about 60% of neurons in the brain, is enriched in numerous plasticity mechanisms, and presents a large variety of antigens at the neuroglial level: ion channels and related proteins, synaptic adhesion/organizing proteins, transmitter receptors, and glial cells. Cerebellar circuitry is especially vulnerable to immune attacks. After the loss of immune tolerance, IMCAs present in an acute or subacute manner with various combinations of a vestibulocerebellar syndrome (VCS), a cerebellar motor syndrome (CMS), and a cerebellar cognitive affective syndrome/Schmahmann's syndrome (CCAS/SS). IMCAs include gluten ataxia (GA), post-infectious cerebellitis (PIC), Miller Fisher syndrome (MFS), paraneoplastic cerebellar degeneration (PCD), opsoclonus myoclonus syndrome (OMS), anti-glutamic acid decarboxylase (anti-GAD) ataxia, and glial fibrillary acidic protein (GFAP) astrocytopathy (GFAPA). In addition, multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), Behçet disease, and collagen-vascular disorders may also present with cerebellar symptoms when lesions involve cerebellar afferences/efferences. Patients whose clinical profiles do not fit with IMCAs are now gathered in the group of primary autoimmune cerebellar ataxias (PACAs). Latent auto-immune cerebellar ataxia (LACA) refers to a clinical stage with a slow progressive course and a lack of obvious auto-immune background. At a pre-symptomatic stage, patients remain asymptomatic, whereas at the prodromal stage aspecific symptoms occur, announcing the symptomatic neuronal loss. LACA corresponds to a time-window where an intervention could lead to preservation of plasticity mechanisms. Patients may evolve from LACA to PACA and typical IMCAs, highlighting a continuum. Immune ataxias represent a model to elucidate the sequence of events leading to destruction of cerebellar neuronal reserve and develop novel strategies aiming to restore plasticity mechanisms. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a condition that affects the nervous system and that requires considerably more in-depth study. Abnormal Nicotinamide Adenine Dinucleotide (NAD+) metabolism and disulfide levels have been demonstrated in AD. This study investigated novel hub genes for disulfide levels and NAD+ metabolism in relation to the diagnosis and therapy of AD. Methods: Data from the gene expression omnibus (GEO) database were analyzed. Hub genes related to disulfide levels, NAD+ metabolism, and AD were identified from overlapping genes for differentially expressed genes (DEGs), genes in the NAD+ metabolism or disulfide gene sets, and module genes obtained by weighted gene co-expression network analysis (WGCNA). Pathway analysis of these hub genes was performed by Gene Set Enrichment Analysis (GSEA). A diagnostic model for AD was constructed based on the expression level of hub genes in brain samples. CIBERSORT was used to evaluate immune cell infiltration and immune factors correlating with hub gene expression. The DrugBank database was also used to identify drugs that target the hub genes. Results: We identified 3 hub genes related to disulfide levels in AD and 9 related to NAD+ metabolism in AD. Pathway analysis indicated these 12 genes were correlated with AD. Stepwise regression analysis revealed the area under the curve (AUC) for the predictive model based on the expression of these 12 hub genes in brain tissue was 0.935, indicating good diagnostic performance. Additionally, analysis of immune cell infiltration showed the hub genes played an important role in AD immunity. Finally, 33 drugs targeting 10 hub genes were identified using the DrugBank database. Some of these have been clinically approved and may be useful for AD therapy. Conclusion: Hub genes related to disulfide levels and NAD+ metabolism are promising biomarkers for the diagnosis of AD. These genes may contribute to a better understanding of the pathogenesis of AD, as well as to improved drug therapy. [ABSTRACT FROM AUTHOR]

Hepatitis B surface antigen (HBsAg) loss or functional cure (FC) is considered the optimal therapeutic outcome for patients with chronic hepatitis B (CHB). However, the immune-pathological biomarkers and underlying mechanisms of FC remain unclear. In this study we comprehensively interrogate disease-associated cell states identified within intrahepatic tissue and matched PBMCs (peripheral blood mononuclear cells) from patients with CHB or after FC, at the resolution of single cells, to provide novel insights into putative mechanisms underlying FC. We combined single-cell transcriptomics (single-cell RNA sequencing) with multiparametric flow cytometry-based immune phenotyping, and multiplexed immunofluorescence to elucidate the immunopathological cell states associated with CHB vs. FC. We found that the intrahepatic environment in CHB and FC displays specific cell identities and molecular signatures that are distinct from those found in matched PBMCs. FC is associated with the emergence of an altered adaptive immune response marked by CD4 cytotoxic T lymphocytes, and an activated innate response represented by liver-resident natural killer cells, specific Kupffer cell subtypes and marginated neutrophils. Surprisingly, we found MHC class II-expressing hepatocytes in patients achieving FC, as well as low but persistent levels of covalently closed circular DNA and pregenomic RNA, which may play an important role in FC. Our study provides conceptually novel insights into the immuno-pathological control of HBV cure, and opens exciting new avenues for clinical management, biomarker discovery and therapeutic development. We believe that the discoveries from this study, as it relates to the activation of an innate and altered immune response that may facilitate sustained, low-grade inflammation, may have broader implications in the resolution of chronic viral hepatitis. This study dissects the immuno-pathological cell states associated with functionally cured chronic hepatitis B (defined by the loss of HBV surface antigen or HBsAg). We identified the sustained presence of very low viral load, accessory antigen-presenting hepatocytes, adaptive-memory-like natural killer cells, and the emergence of helper CD4 T cells with cytotoxic or effector-like signatures associated with functional cure, suggesting previously unsuspected alterations in the adaptive immune response, as well as a key role for the innate immune response in achieving or maintaining functional cure. Overall, the insights generated from this study may provide new avenues for the development of alternative therapies as well as patient surveillance for better clinical management of chronic hepatitis B. [Display omitted] • An altered adaptive immune response – associated with CD4 cytotoxic T lymphocytes – emerges in functionally cured patients. • Increased recruitment and margination of neutrophils in the liver suggests a low grade immune active state linked to functional cure. • MHC class II-expressing hepatocytes were identified as accessory antigen-presenting cells. • Alterations in the immuno-pathological cell states identified in the liver environment are not always reflected in peripheral circulation. [ABSTRACT FROM AUTHOR]

[Objectives] Previous studies had found that dietary supplementation of 250-1 000 mg·kg-1 rutin could improve the growth performance of broilers at 21 days of age. This study further investigated the effects of rutin on jejunal morphology, mucosal barrier function and antioxidant capacity of broilers. [Methods] A total of 256 1-day-old male Arbor Acres (AA) broilers with similar body weight (43±1) g were randomly divided into 4 groups with 8 replicates per group and 8 chickens per pen. Broilers in the control group were fed a basal diet, and those in experimental groups were fed the basal diet supplemented with 250, 500 and 1 000 mg·kg-1 rutin, respectively. At 21 days of age, one broiler from each replicate was chosen and slaughtered to analyze the indices of intestinal barrier function, immune inflammation, and antioxidant capacity and other related indices. [Results] Compared with the control group, dietary 250 mg·kg-1 rutin significantly increased spleen organ index, total superoxide dismutase (T-SOD) activity and total antioxidant capacity (T-AOC) of jejunal mucosa and closed small cyclic protein-1 (ZO-1) in jejunal mucosa of broilers, blocking protein (OCLN), nuclear factor E2-related factor 2 (Nrf2) and SOD mRNA expression levels, while serum tumor necrosis faction-α (TNF-α) and D-lactic acid (D-LA) levels, and the expression of TNF-α mRNA in jejunal mucosa significantly decreased (PT<0.05). Compared with the control group, dietary 500 mg·kg-1 rutin significantly increased bursal organ index, jejunum VH/CD value, T-SOD activity and T-AOC in jejunal mucosa, B-cell lymphoma gene-2 (Bcl-2), ZO-1 and Nrf2 mRNA expressions in jejunal mucosa of broilers. The serum TNF-α level significantly decreased (PT<0.05). Compared with the control group, 250 and 500 mg·kg-1 rutin group, dietary 1 000 mg·kg-1 rutin supplementation significantly increased the serum immunoglobulin M (IgM) and immunoglobulin G (IgG) contents (PT<0.05). Compared with 500 mg·kg-1 rutin group, dietary 250 mg·kg-1 rutin significantly increased spleen organ index, serum lipopolysaccharide (LPS) level and OCLN mRNA expression level, and serum D-LA level of broilers significantly decreased (PT<0.05). Compared with 1 000 mg·kg-1 rutin group, dietary 250 mg·kg-1 rutin significantly increased spleen organ index, and TNF-α mRNA expression level in jejunal mucosa of broilers decreased (PT<0.05). Compared with 1 000 mg·kg-1 rutin group, dietary 500 mg·kg-1 rutin significantly increased the expression of Bcl-2 mRNA level in jejunal mucosa, and the serum LPS level of broilers significantly decreased (PT<0.05). [Conclusions] Dietary supplementation of 250 mg·kg-1 or 500 mg·kg-1 rutin could promote the development of immune organs, enhance immune capacity, improve jejunum morphology, and enhance jejunum barrier function of broilers. The improvement of antioxidant function of jejunum of broilers might be related to the activation of Nrf2 signaling pathway. The optimum dosage of rutin was 250 mg·kg-1 under the experimental conditions. [ABSTRACT FROM AUTHOR]

Immune check-point inhibitors (ICPi) are immunomodulating agents, which have revolutionized the management of advanced metastatic cancers. Being immunomodulating agents, they are predisposed to causing colitis. This descriptive review article emphasized on the management of ICPi-associated colitis in advanced metastatic cancers. We used PubMed, Google Scholar, Scopus, and Embase databases for literature review, and terminologies commonly searched were "management," "immune check-point inhibitors," "colitis," "metastatic," "cancers," "literature," and "review." We reviewed a total of 11 articles done in the last 15 years relevant to ICPi colitis and its management; all the articles showed that diarrhea and colitis are the most common adverse effects observed in patients on ICPi, but prior to establishing the diagnosis of ICPi-causing colitis, possibility of Clostridium difficle or cytomegalovirus infections should be ruled out. Once the diagnosis of ICPi colitis is established, treatment should be started depending upon the severity of colitis. In mild severity, discontinuation of ICPi can resolve the symptoms but, in most of the patients with moderate to high severity of colitis, corticosteroids are considered a cornerstone treatment. Patients unresponsive to steroid treatment should be re-evaluated for infections after which anti-TNF therapy--infliximab or vedolizumab, cyclosporine, mycophenolate mofetil--can be considered. [ABSTRACT FROM AUTHOR]

Bivalves play a key role in aquatic ecosystems and are a valuable commercial resource. The prosperity of these aquatic organisms depends mainly on the effectiveness of their immune defense, in which the hemolymph plays a central role. Hemolymph may be used as an effective non-lethal criterion of health. However, the predictive value of hemolymph analysis depends on the comparison between the obtained results and reference data from healthy individuals living in natural aquatic environments. We collected hemolymph from 15 commercially important species from wild populations at stations located in non-impacted and impacted water areas of the Sea of Japan. Of the 11 hemolymph parameters we analyzed, the total hemocyte count, percentage of hemocyte types, phagocytic activity, presence of reactive oxygen species, and protein concentration differed significantly between populations from non-impacted and impacted water areas. The most responsive species to pollution were Magallana gigas, Crenomytilus grayanus, Mizuhopecten yessoensis, and Mactra chinensis. This work is the first to examine a large number of commercially important species simultaneously. The results of this study are the basis for establishing the health status criteria of commercial bivalves for veterinary control in aquaculture and biomonitoring. [ABSTRACT FROM AUTHOR]

Aim: Although many studies have explored the link between inflammatory markers and psychosis, there is a paucity of research investigating the temporal progression in individuals at clinical high‐risk (CHR) who eventually develop full psychosis. To address this gap, we investigated the correlation between serum cytokine levels and Timeframe for Conversion to Psychosis (TCP) in individuals with CHR. Methods: We enrolled 53 individuals with CHR who completed a 5‐year follow‐up with a confirmed conversion to psychosis. Granulocyte macrophage‐colony stimulating factor (GM‐CSF), interleukin (IL)‐1β, 2, 6, 8, 10, tumor necrosis factor‐α (TNF‐α), and vascular endothelial growth factor (VEGF) levels were measured at baseline and 1‐year. Correlation and quantile regression analyses were performed. Results: The median TCP duration was 14 months. A significantly shorter TCP was associated with higher levels of TNF‐α (P = 0.022) and VEGF (P = 0.016). A negative correlation was observed between TCP and TNF‐α level (P = 0.006) and VEGF level (P = 0.04). Quantile regression indicated negative associations between TCP and GM‐CSF levels below the 0.5 quantile, IL‐10 levels below the 0.3 quantile, IL‐2 levels below the 0.25 quantile, IL‐6 levels between the 0.65 and 0.75 quantiles, TNF‐α levels below the 0.8 quantile, and VEGF levels below the 0.7 quantile. A mixed linear effects model identified significant time effects for IL‐10 and IL‐2, and significant group effects for changes in IL‐2 and TNF‐α. Conclusions: Our findings underscore that a more pronounced baseline inflammatory state is associated with faster progression of psychosis in individuals with CHR. This highlights the importance of considering individual inflammatory profiles during early intervention and of tailoring preventive measures for risk profiles. [ABSTRACT FROM AUTHOR]

Background: Osteomyelitis (OM) is recognized as a significant challenge in orthopedics due to its complex immune and inflammatory responses. The prognosis heavily depends on timely diagnosis, accurate classification, and assessment of severity. Thus, the identification of diagnostic and classification‐related genes from an immunological standpoint is crucial for the early detection and tailored treatment of OM. Methods: Transcriptomic data for OM was sourced from the Gene Expression Omnibus (GEO) database, leading to the identification of autophagy‐ and immune‐related differentially expressed genes (AIR‐DEGs) through differential expression analysis. Diagnostic and classification models were subsequently developed. The CIBERSORT algorithm was utilized to examine immune cell infiltration in OM, and the relationship between OM clusters and various immune cells was explored. Key AIR‐DEGs were further validated through the creation of OM animal models. Results: Analysis of the transcriptomic data revealed three AIR‐DEGs that played a significant role in immune responses and pathways. Nomogram and receiver operating characteristic curve analyses were performed, demonstrating excellent diagnostic capability for differentiating between OM patients and healthy individuals, with an area under the curve of 0.814. An unsupervised clustering analysis discerned two unique patterns of autophagy‐ and immune‐related genes, as well as gene patterns. Further exploration into immune infiltration exhibited notable variances across different subtypes, especially between OM cluster 1 and gene cluster A, highlighting their potential role in mitigating inflammatory responses by regulating immune activities. Moreover, the mRNA and protein expression levels of three AIR‐DEGs in the animal model were aligned with those in the training and validation data sets. Conclusions: From an immunological perspective, a diagnostic model was successfully developed, and two distinct clustering patterns were identified. These contributions offer a significant resource for the early detection and personalized immunotherapy of patients with OM. [ABSTRACT FROM AUTHOR]

Maternal obesity results in increased placental oxidative stress, antioxidant production, and fatty acid mishandling. It also leads to placental leukocyte infiltration and proinflammatory response in some studies. Maternal obesity is linked to increased fetal circulating inflammatory markers and decreased immune response to pathogens. There are also programmed changes related to oxidative damage and hepatic steatosis in the offspring of obese mothers, with males appearing more affected. Promising data show increased physical activity, decreased sedentary time, and serine supplementation during pregnancy were able to correct placental and offspring oxidative stress damage induced by maternal obesity during pregnancy. The obesity epidemic has led to a growing body of research investigating the consequences of maternal obesity on pregnancy and offspring health. The placenta, traditionally viewed as a passive intermediary between mother and fetus, is known to play a critical role in modulating the intrauterine environment and fetal development, and we now know that maternal obesity leads to increased inflammation, oxidative stress, and altered placental function. Here, we review recent research exploring the involvement of inflammation and oxidative stress as mechanisms impacting the placenta and fetus during obese pregnancy. Understanding them is crucial for informing strategies that can mitigate the adverse health effects of maternal obesity on offspring development and disease risk. [ABSTRACT FROM AUTHOR]

Introduction: Night shift work disrupts circadian rhythms and has been associated with immune system alterations and various health conditions. However, there is limited data regarding its impact on psoriasis. The aim of our study was to compare psoriasis severity and the hormonal and immunological profile in patients with a night shift work to those with a daytime occupation. Methods: In this case-control study, we enrolled psoriatic patients aged >18 years engaged in night shift work and a control group of psoriatic patients with a daytime occupation. A further categorization was performed by the duration of night shift work: < or ≥7 days a month and < or ≥8 years. Disease severity was evaluated by PASI, BSA, and DLQI, and blood samples were taken to measure various hormonal and immunological markers. Univariable and multivariable analysis were performed to assess differences between the two groups. Results: A total of 40 night shift workers were included, along with 36 patients in the control group. Patients who worked night shifts at least 7 days a month had significantly higher PASI scores (11.2 ± 6.6 vs. 8.5 ± 6.6; p = 0.04) and higher IL-8 serum (115.33 ± 463.65 pg/mL vs. 19.98 ± 29.78 pg/mL; p = 0.006) compared to patients who did not. Night shifts workers for at least 8 years had higher BMI (28.65 ± 4.56 vs. 25.32 ± 5.50, p = 0.010), and females had higher testosterone levels (0.46 ± 0.53 ng/mL vs. 0.23 ± 0.13 ng/mL; p = 0.055). Conclusion: Night shift might increase psoriasis severity and have an impact on chronic inflammation, obesity, and hormonal imbalances. [ABSTRACT FROM AUTHOR]

Polysaccharides from natural sources have an excellent immune function and low toxicity; however, their limitations such as short half‐life and instability limit their sustained pharmacological activity. In this context, the combination of polysaccharides and nanotechnology have been developed to promote the stability and prolong the immune activities of polysaccharides. To synthesize and explore the antitumor effect and immunomodulatory activity of PHP‐AuNPs. Polysaccharides extracted from Pseudostellaria heterophylla were used to synthesize gold nanocomposites (PHP‐AuNPs), and their physicochemical properties and immunoregulatory effect in vitro and in vivo were analyzed. The PHP‐AuNPs were green synthesized with high biosafety. PHP‐AuNPs can activate macrophages in vitro and decrease the tumor weight and volume, whereas they increase the immune organ index in vivo. Besides, PHP‐AuNPs showed a beneficial effect for maintaining the immune balance of CD4+/CD8+ T cells and modulating the release of cytokines such as TNF‐α increase and IL‐10 decrease in mice. All these results suggested that PHP‐AuNPs exhibit a remarkable antitumor effect and stronger immunomodulatory activity than that of free PHP‐1. Research Highlights: The P. heterophylla polysaccharide‐gold nanocomposites (PHP‐AuNPs) were synthesized and physicochemical properties were characterized.The cytotoxicity in vitro and immunomodulatory effects of PHP‐AuNPs on macrophages were analyzed.The immune‐antitumor effects in vivo of PHP‐AuNPs have also been confirmed. [ABSTRACT FROM AUTHOR]

Background. Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer, and while advancements in diagnosis, surgery, radiotherapy, and molecular therapy have improved clinical prognosis, the long-term survival rate and quality of life of patients remain unsatisfactory. Therefore, identifying new prognostic biomarkers and potential therapeutic targets is crucial. Objectives. This study aimed to analyze the role of anoikis-related gene characteristics in LUAD. Materials and methods. The anoikis-related genes were obtained from the GeneCards database. Genetic expression data and clinical characteristic information were collected from The Cancer Genome Atlas (TCGA)-LUAD, and the Gene Expression Omnibus (GEO) GSE31210, GSE37745, and GSE68465 datasets. Random survival forest and least absolute shrinkage and selection operator (LASSO) models were applied to construct the risk model. An analysis of immune cell infiltration and function was performed with the scores. Results. Four prognosis-related genes (TLE1, GLI2, PLK1, and BAK1) were obtained and used to construct the anoikis score. We found that the patient survival rate was higher in the low-anoikis score (LAS) group. Moreover, both the stromal and immune scores were negatively correlated with the anoikis score. With the increase of the anoikis score, the levels of natural killer cells, regulatory T cells, CD4+ T cells, CD8+ T cells, B cells, and macrophages decreased. The anoikis score had a negative regulatory relationship with the immune response, natural killer cell activation and T cell activation. The TP53 mutation was significant in LUAD patients and was present in 56% of the high-anoikis score (HAS) group and in 40% of the LAS group. Conclusions. The anoikis score was associated with poor prognosis in LUAD patients. Anoikis-related genes were associated with tumor immune dysregulation and TP53 mutation in LUAD. This study opens a new perspective for LUAD therapy. [ABSTRACT FROM AUTHOR]

Purpose: Immune checkpoint inhibitors (ICIs) in combination with chemotherapy have showed its benefits in clinical studies, and here we conducted a further evaluation on the safety and efficacy of this treatment strategy. Methods: A systematic literature review was conducted in PubMed, Embase and Cochrane Library to identify clinical studies on ICIs and chemotherapy for metastatic breast cancer. The primary efficacy endpoints were progression-free survival (PFS) and overall survival (OS), and adverse events (AEs) were analyzed. Random or fixed effects models were used to estimate pooled Hazard ratio (HR), odds ratio (OR) and the data of 95% confidence interval (CI) depend on the Heterogeneity. Cochrane risk assessment tool was used to assess risk of bias. We also drew forest plots and funnel plots, respectively. Results: Seven studies with intend-to-treat (ITT) population for 3255 patients were analyzed. ICIs pooled therapy showed clinical benefits compared with chemotherapy alone, improving PFS (HR = 0.81, 95% CI: 0.74–0.90) of patients with metastatic triple negative breast cancer (mTNBC), especially in patients with PD-L1-positive tumors. However, it had no effect on OS (HR = 0.92, 95% CI 0.85–1.01). Besides, mTNBC patients received pooled therapy were less frequently to have AEs (OR = 1.30, 95% CI: 1.09–1.54). In patients with metastatic Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancer, pooled therapy showed no benefit for PFS (HR = 0.80, 95% CI: 0.50–1.28) and OS (HR = 0.87, 95% CI: 0.48–1.58). Conclusion: Pooled therapy had improved PFS in mTNBC patients, especially in patients with PD-L1-positive tumors, and it was less likely to cause grade ≥ 3 AEs. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukemia, constituting a majority of leukemias, grapples with a 24% 5-year survival rate. Recent strides in research have unveiled fresh targets for drug therapies. LIM-only, a pivotal transcription factor within LIM proteins, oversees cell development and is implicated in tumor formation. Among these critical LIM proteins, CSRP1, a Cysteine-rich protein, emerges as a significant player in various diseases. Despite its recognition as a potential prognostic factor and therapeutic target in various cancers, the specific link between CSRP1 and acute myeloid leukemia remains unexplored. Our previous work, identifying CSRP1 in a prognostic model for AML patients, instigates a dedicated exploration into the nuanced role of CSRP1 in acute myeloid leukemia. Methods: R tool was conducted to analyze the public data. qPCR was applied to evaluate the expression of CSRP1 mRNA for clinical samples and cell line. Unpaired t test, Wilcoxon Rank Sum test, KM curves, spearman correlation test and Pearson correlation test were included in this study. Results: CSRP1 displays notable expression variations between normal and tumor samples in acute myeloid leukemia (AML). It stands out as an independent prognostic factor for AML patients, showing correlations with clinical factors like age and cytogenetics risk. Additionally, CSRP1 correlates with immune-related pathways, immune cells, and immune checkpoints in AML. Furthermore, the alteration of CSRP1 mRNA levels is observed upon treatment with a DNMT1 inhibitor for THP1 cells. Conclusion: The CSRP1 has potential as a novel prognostic factor and appears to influence the immune response in acute myeloid leukemia. Additionally, there is an observed association between CSRP1 and DNA methylation in acute myeloid leukemia. [ABSTRACT FROM AUTHOR]

Background: The nervous system is central to coordinating behavioural responses to environmental change, likely including ocean acidification (OA). However, a clear understanding of neurobiological responses to OA is lacking, especially for marine invertebrates. Results: We evaluated the transcriptomic response of the central nervous system (CNS) and eyes of the two-toned pygmy squid (Idiosepius pygmaeus) to OA conditions, using a de novo transcriptome assembly created with long read PacBio ISO-sequencing data. We then correlated patterns of gene expression with CO2 treatment levels and OA-affected behaviours in the same individuals. OA induced transcriptomic responses within the nervous system related to various different types of neurotransmission, neuroplasticity, immune function and oxidative stress. These molecular changes may contribute to OA-induced behavioural changes, as suggested by correlations among gene expression profiles, CO2 treatment and OA-affected behaviours. Conclusions: This study provides the first molecular insights into the neurobiological effects of OA on a cephalopod and correlates molecular changes with whole animal behavioural responses, helping to bridge the gaps in our knowledge between environmental change and animal responses. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of vitiligo remains elusive. Emerging evidence suggests that vitiligo is an immune-mediated disorder, in which a plethora of immune cells play pivotal roles. However, the association between circulating immune cells and vitiligo continues to be enigmatic. Materials and methods: We extracted single nucleotide polymorphisms (SNPs) associated with immune circulating cells at a genome-wide significance level from the BLOOD CELL CONSORTIUM’s genome-wide association study (GWAS) dataset. Summary data for 385,801 cases of vitiligo were obtained from a largescale Finnish genome-wide association study (ncases=292, ncontrols=385,509). The inverse variance weighted (IVW) method was employed as the primary analytical approach for Mendelian randomization (MR) analysis. Additionally, heterogeneity was assessed using Cochran’s Q value, and horizontal pleiotropy was evaluated using MR-Egger Mendelian Randomization Pleiotropy RESidual Sum and Outlier and leave-one-out analyses. Results: The risk of vitiligo was found to increase with the elevation of 4 circulating immune cells, as evidenced by the odds ratios (ORs) and 95% confidence intervals (CIs): basophils (OR=1.81; 95% CI: 1.01–3.24, p=0.0450), monocytes (OR=1.67; 95% CI: 1.23–2.26, p=0.0009), eosinophils (OR=1.78; 95% CI: 1.22–2.59, p=0.0028), and neutrophils (OR=1.65; 95% CI: 1.08–2.54, p=0.0208). After removing outliers, the sensitivity analysis of the above indicators did not show heterogeneity and pleiotropy. Conclusion: Our findings illuminate the association between circulating immune cells and vitiligo, offering insights that could guide clinical practices in the treatment of vitiligo. [ABSTRACT FROM AUTHOR]

Skeletal muscle (SKM), despite comprising ~40% of body mass, rarely manifests cancer. This review explores the mechanisms that help to explain this rarity, including unique SKM architecture and function, which prohibits the development of new cancer as well as negates potential metastasis to SKM. SKM also presents a unique immune environment that may magnify the anti-tumorigenic effect. Moreover, the SKM microenvironment manifests characteristics such as decreased extracellular matrix stiffness and altered lactic acid, pH, and oxygen levels that may interfere with tumor development. SKM also secretes anti-tumorigenic myokines and other molecules. Collectively, these mechanisms help account for the rarity of SKM cancer. [ABSTRACT FROM AUTHOR]

IL33 plays an important role in cancer. However, the role of liver cancer remains unclear. Open‐accessed data was obtained from the Cancer Genome Atlas, Xena, and TISCH databases. Different algorithms and R packages are used to perform various analyses. Here, in our comprehensive study on IL33 in HCC, we observed its differential expression across cancers, implicating its role in cancer development. The single‐cell analysis highlighted its primary expression in endothelial cells, unveiling correlations within the HCC microenvironment. Also, the expression level of IL33 was correlated with patients survival, emphasizing its potential prognostic value. Biological enrichment analyses revealed associations with stem cell division, angiogenesis, and inflammatory response. IL33's impact on the immune microenvironment showcased correlations with diverse immune cells. Genomic features and drug sensitivity analyses provided insights into IL33's broader implications. In a pan‐cancer context, IL33 emerged as a potential tumour‐inhibitor, influencing immune‐related molecules. This study significantly advances our understanding of IL33 in cancer biology. IL33 exhibited differential expression across cancers, particularly in endothelial cells within the HCC microenvironment. IL33 is correlated with the survival of HCC patients, indicating potential prognostic value and highlighting its broader implications in cancer biology. [ABSTRACT FROM AUTHOR]

Sperm-associated antigen 5 (SPAG5) regulates cancer cell invasion and is involved in the progression of many cancers. However, the role of SPAG5 in endometrial carcinoma (EC) is still unknown. The purpose of this study was to explore the role of SPAG5 in EC and its potential molecular mechanism. The UALCAN tool and cBioPortal were used to analyze the expression and alterations of SPAG5 in EC, respectively. OncoLnc was used for survival analysis. We analyzed the effects of SPAG5 on immune cell infiltration and the expression levels of immune checkpoints. We also overexpressed and knocked down SPAG5 in EC cells to explore the effect of SPAG5 regulation on migration, invasion, apoptosis, and the cell cycle of EC cells. We found that SPAG5 was overexpressed and the SPAG5 gene was often mutated in EC. High SPAG5 expression was significantly associated with poor overall survival in patients with EC. SPAG5 also affected the level of immune cell infiltration in the TIME and the expression of immune checkpoints lymphocyte activating 3 (LAG3) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) in patients with EC. It may also be involved in the immunotherapy response in these patients. In vitro experiments showed that SPAG5 promotes cancer cell migration and invasion. In conclusion, this study lays the foundation for further understanding the molecular mechanisms of EC involving SPAG5 and contributes to diagnosing and managing this disease. [ABSTRACT FROM AUTHOR]

Objective To explore the effect of mixed antibiotics on the intestinal flora of mice to affect the immune regulation of the body, explore the role of intestinal flora in the development of obesity, and provide new ideas and ways for the prevention and treatment of obesity. Methods Seventy-two 10-week-old male C57BL/6 mice were randomly divided into blank control (Ctrl) group, high-fat diet (HF) group, antibiotic (ABX) group, and combined (COMB) group (n = 18). At the first 2 weeks (lavage intervention weeks), Ctrl and HF group were given normal saline gavage; ABX and COMB group were given mixed antibiotics gavage, and the gavage volume was 0.2 mL/animal/day. For the following 8 weeks (feeding weeks), Ctrl and ABX group were fed with ordinary diet, HF and COMB group were fed with high-fat diet. Body weight was measured weekly, and fasting blood glucose was measured before and after gavage, and at the 4th and 8th week of feeding. Oral glucose tolerance test was performed at the end of the experiment. The organ coefficient was measured and the cell morphology of white and brown adipose tissue was observed. Serum was collected for the determination of free fatty acid, high-density lipoprotein, low-density lipoprotein, triglyceride, and total cholesterol. Serum TNF- a, IL-10, IL-4, IL-13, IL-33 and MCP-1 was detected by ELISA. The stool of mice was collected for second generation sequencing. Results High-fat diet increased body weight, serum total cholesterol, low-density lipoprotein, IL-13, IL-33, TNF-α, MCP-1 content, and decreased glucose tolerance and organ coefficient in mice (P < 0.05). From the first feeding week to the end of the experiment, body weight in COMB group was significantly lower than that in HF group (P < 0.05). The level of glucose tolerance, serum total cholesterol, low density lipoprotein, IL-13, IL-33, TNF-α and MCP-1 in COMB group was lower than those in HF group (P < 0.05). The α diversity of intestinal flora in ABX group was lower than that in Ctrl group (P < 0.05). Congestion and bleeding in WAT were obvious in HF group, but not in COMB group. The microbial community composition of ABX and HF group was similar to that of Ctrl and COMB group, respectively. Conclusion High-fat diet induces obesity, disorder of glucose and lipid metabolism and inflammation in mice. Short-term mixed antibiotic use can regulate the intestinal flora of mice, mediate increased expression of related anti-inflammatory factors, up-regulate host immunity, and improve glucose and lipid metabolism in mice. [ABSTRACT FROM AUTHOR]

Bacterial extracellular vesicles (EVs) are crucial mediators of information transfer between bacteria and host cells. Macrophages, as key effector cells in the innate immune system, have garnered widespread attention for their interactions with bacterial EVs. Increasing evidence indicates that bacterial EVs can be internalized by macrophages through multiple pathways, thereby influencing their immune functions. These functions include inflammatory responses, antimicrobial activity, antigen presentation, and programmed cell death. Therefore, this review summarizes current research on the interactions between bacterial EVs and macrophages. This will aid in the deeper understanding of immune modulation mediated by pathogenic microorganisms and provide a basis for developing novel antibacterial therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background and objectives: The oral and gut microbiota play significant roles in childhood asthma pathogenesis. However, the communication dynamics and pathogenic mechanisms by which oral microbiota influence gut microbiota and disease development remain incompletely understood. This study investigated potential mechanisms by which oral-originated gut microbiota, specifically Prevotella genus, may contribute to childhood asthma etiology. Methods: Oral swab and fecal samples from 30 asthmatic children and 30 healthy controls were collected. Microbiome composition was characterized using 16S rRNA gene sequencing and metagenomics. Genetic distances identified potential oral-originated bacteria in asthmatic children. Functional validation assessed pro-inflammatory properties of in silico predicted microbial mimicry peptides from enriched asthma-associated species. Fecal metabolome profiling combined with metagenomic correlations explored links between gut microbiota and metabolism. HBE cells treated with Prevotella bivia culture supernatant were analyzed for lipid pathway impacts using UPLC-MS/MS. Results: Children with asthma exhibited distinct oral and gut microbiota structures. Prevotella bivia, P. disiens, P. oris and Bacteroides fragilis were enriched orally and intestinally in asthmatics, while Streptococcus thermophilus decreased. P. bivia, P. disiens and P. oris in asthmatic gut likely originated orally. Microbial peptides induced inflammatory cytokines from immune cells. Aberrant lipid pathways characterized asthmatic children. P. bivia increased proinflammatory and decreased anti-inflammatory lipid metabolites in HBE cells. Conclusion: This study provides evidence of Prevotella transfer from oral to gut microbiota in childhood asthma. Prevotella's microbial mimicry peptides and effects on lipid metabolism contribute to disease pathogenesis by eliciting immune responses. Findings offer mechanistic insights into oral-gut connections in childhood asthma etiology. [ABSTRACT FROM AUTHOR]

FAT1, a substantial transmembrane protein, plays a pivotal role in cellular adhesion and cell signaling. Numerous studies have documented frequent alterations in FAT1 across various cancer types, with its aberrant expression being linked to unfavorable survival rates and tumor progression. In the present investigation, we employed bioinformatic analyses, as well as in vitro and in vivo experiments to elucidate the functional significance of FAT1 in pan-cancer, with a primary focus on lung cancer. Our findings unveiled FAT1 overexpression in diverse cancer types, including lung cancer, concomitant with its association with an unfavorable prognosis. Furthermore, FAT1 is intricately involved in immune-related pathways and demonstrates a strong correlation with the expression of immune checkpoint genes. The suppression of FAT1 in lung cancer cells results in reduced cell proliferation, migration, and invasion. These collective findings suggest that FAT1 has potential utility both as a biomarker and as a therapeutic target for lung cancer. [ABSTRACT FROM AUTHOR]

Background: Sex differences in the brain may play an important role in sex-differential prevalence of neuropsychiatric conditions. Methods: In order to understand the transcriptional basis of sex differences, we analyzed multiple, large-scale, human postmortem brain RNA-Seq datasets using both within-region and pan-regional frameworks. Results: We find evidence of sex-biased transcription in many autosomal genes, some of which provide evidence for pathways and cell population differences between chromosomally male and female individuals. These analyses also highlight regional differences in the extent of sex-differential gene expression. We observe an increase in specific neuronal transcripts in male brains and an increase in immune and glial function-related transcripts in female brains. Integration with single-nucleus data suggests this corresponds to sex differences in cellular states rather than cell abundance. Integration with case–control gene expression studies suggests a female molecular predisposition towards Alzheimer's disease, a female-biased disease. Autism, a male-biased diagnosis, does not exhibit a male predisposition pattern in our analysis. Conclusion: Overall, these analyses highlight mechanisms by which sex differences may interact with sex-biased conditions in the brain. Furthermore, we provide region-specific analyses of sex differences in brain gene expression to enable additional studies at the interface of gene expression and diagnostic differences. Highlights: Numerous but small autosomal sex differences in expression exist in all brain regions tested. Autosomal genes with enriched expression in males are enriched in neuronal pathways. Autosomal genes with enriched expression in females are enriched with immune system functions. Integration with single-nucleus datasets suggest these differences are more likely related to cell state differences than cell number differences. The female cortex shows an enrichment of genes expressed in Alzheimer's disease brains. Plain English Summary: We sought to understand why females have higher rates of Alzheimer's disease, and males have higher rates of autism. One idea was that the female brain at baseline may be more similar to an Alzheimer's brain, so it is easier for them to shift into that state (likewise, males may be more similar to autism). To test this, we examined gene expression differences between brains of biological males and biological females. While all people have the same ~ 25,000 genes, each gene can be on or off ('expressed') to different extents. Overall, we found that there were differences in gene expression between males and females in all brain regions tested but more differences in some brain regions than others. By looking at the role of these genes we estimate that female immune system processes might be more active in the brain. We also found female brain gene expression looked slightly more like people with Alzheimer's compared to people without Alzheimer's, which may explain why females get Alzheimer's disease more easily. However, the male brain gene expression did not look more like autism, suggesting that the reason males have higher rates of autism is complex and needs further investigation. [ABSTRACT FROM AUTHOR]

Background: This study aimed to employ plasma proteomics to investigate the molecular changes, pathway alterations, and potential novel biochemical markers associated with balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods: Pre- and post-BPA plasma samples from five CTEPH patients in the PRACTICE study were analyzed to identify differentially expressed proteins. Proteomic and bioinformatics analyses were conducted, and the identified proteins were further validated using ELISA assays in a separate cohort of the same study. Correlation and multivariate regression analyses were performed to investigate the associations between these differentially expressed proteins and clinical parameters. Results: Significantly higher serum levels of asialoglycoprotein receptor 2 (ASGR2) were detected in 5 CTEPH patients compared to those in healthy individuals but decreased significantly after successful BPA procedures. The decrease in serum levels of ASGR2 after the completion of BPA procedures was further validated in a separate cohort of 48 patients with CTEPH [0.70 (0.51, 1.11) ng/mL vs. 0.38 (0.27, 0.59) ng/mL, P < 0.001]. Significant associations were found between the pre-BPA ASGR2 level and clinical parameters, including neutrophil percentage (R = 0.285, P < 0.05), platelet (PLT) count (R = 0.386, P < 0.05), and high-density lipoprotein cholesterol (HDL-C) before BPA (R = -0.285, P < 0.05). Significant associations were detected between post-BPA serum ASGR2 levels and lymphocyte percentage (LYM%) (R = 0.306, P < 0.05), neutrophil-to-lymphocyte ratio (R = -0.294, P < 0.05), and pulmonary vascular resistance after BPA (R = -0.35, P < 0.05). Multivariate stepwise regression analysis revealed that pre-BPA ASGR2 levels were associated with HDL-C and PLT count (both P < 0.001), while post-BPA ASGR2 levels were associated with LYM% (P < 0.05). Conclusion: Serum levels of ASGR2 may be a biomarker for the effectiveness of BPA treatment in CTEPH patients. The pre-BPA serum level of ASGR2 in CTEPH patients was associated with HDL-C and the PLT count. The post-BPA serum level of ASGR2 was correlated with the LYM%, which may reflect aspects of immune and inflammatory status. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer remains a significant gynecologic malignancy in both China and the United States, posing a substantial threat to women's lives and health due to its high morbidity and mortality rates. Altered energy metabolism and dysregulated mitochondrial function play crucial roles in the development, growth, metastasis, and recurrence of malignant tumors. In this study, we aimed to predict prognosis and assess efficacy of anti-tumor therapy in cervical cancer patients based on differential genes associated with mitochondrial metabolism. Methods: Transcriptomic data and clinical profiles of cervical cancer patients were retrieved from the TCGA and GEO databases. Differential gene-related cellular pathways were identified through GO, KEGG, and GSEA analyses. Prognostic indices were constructed using LASSO regression analysis. Immune cell infiltration was assessed using CIBERSORT and ssGSEA, and the correlation between immune checkpoint inhibitor genes and differential genes was examined. Tumor mutation load (TMB) and its association with prognostic indices were analyzed using nucleotide variant data from the TCGA database. Patient response to immunotherapy and sensitivity to antitumor drugs were determined using the TIDE algorithm and the oncoPredic algorithm, respectively. Results: A prognostic index based on metabolism-related differential genes was developed to predict the clinical outcome of cervical cancer patients, enabling their classification into two distinct subtypes. The prognostic index emerged as an independent risk factor for unfavorable prognosis. The high-index group exhibited a significantly worse overall prognosis, along with elevated tumor mutation burden (TMB), increased immune cell infiltration, and lower TIDE scores, indicating a potential benefit from immunotherapy. Conversely, the low-index group demonstrated increased sensitivity to metabolism-related antitumor agents, specifically multikinase inhibitors. Conclusion: The aim of this study was to develop a prognostic index based on differential genes associated with mitochondrial metabolism, which could be used to predict cervical cancer patients' prognoses. When combined with TIDE and TMB analyses, this prognostic index offers insights into the immune cell infiltration landscape, as well as the potential efficacy of immunotherapy and targeted therapy. Our analysis suggests that the Iron-Sulfur Cluster Assembly Enzyme (ISCU) gene holds promise as a biomarker for cervical cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: The gut microbiome, a complex microbial community, is intricately linked to the host's genetic background. The regulatory role of host genes on the microbiome has garnered considerable attention due to its impact not only on physiological and immune responses but also on the composition and functionality of intestinal microbes and the overall immune system. Nitric oxide synthase (NOS), through the production of nitric oxide (NO), participates in host defense, immune regulation, inflammatory responses, and autoimmune diseases. However, the effects of NOS on the composition and function of the zebrafish gut microbiota and the regulation of its homeostasis remain unclear. Genomic editing technologies have enabled the creation of zebrafish with specific genetic defects, making them a recognized model for studying host–microbiome–immune interactions. In this study, we characterized the impact of inducible nitric oxide synthase (iNOS) deficiency on the gut microbiota of zebrafish through 16S rRNA amplicon sequencing. Results revealed significant alterations in the microbial diversity and abundance in iNOS-deficient zebrafish, notably a reduction in Vibrio and an increase in Aeromonas. Transcriptomic sequencing of the gut confirmed functional changes, showing significant alterations in pathways related to the complement and coagulation cascades, PPAR signaling, cell adhesion molecules, Staphylococcus aureus infection, steroid synthesis, and bile acid synthesis. These pathways are crucial in pathogen clearance, inflammatory responses, and immune regulation, highlighting the significant role of the iNOS gene not only in microbial composition but also in gut immune and metabolic functions. The gut microbiota constitutes a complex ecosystem that has an important impact on host health. In this study, genetically engineered zebrafish with inducible nitric oxide synthase (iNOS or NOS2) knockout were used as a model to investigate the effects of nos2a/nos2b gene single knockout and nos2 gene double knockout on intestinal microbiome composition and function. Extensive 16S rRNA sequencing revealed substantial changes in microbial diversity and specific taxonomic abundances, yet it did not affect the functional structure of the intestinal tissues. Notably, iNOS-deficient zebrafish demonstrated a decrease in Vibrio species and an increase in Aeromonas species, with more pronounced effects observed in double knockouts. Further transcriptomic analysis of the gut in double iNOS knockout zebrafish indicated significant alterations in immune-related and metabolic pathways, including the complement and PPAR signaling pathways. These findings underscore the crucial interplay between host genetics and gut microbiota, indicating that iNOS plays a key role in modulating the gut microbial ecology, host immune system, and metabolic responses. [ABSTRACT FROM AUTHOR]