Search

Recurrent pregnancy Loss (RPL)is a frequent and upsetting condition. Besides the prevalent cause of RPL including chromosomal defects in the embryo,the effect of translational elements like alterations of epigenetics are of great importance. The emergence of epigenetics has offered a fresh outlook on the causes and treatment of RPL by focusing on the examination of DNA methylation. RPL may arise as a result of aberrant DNA methylation of imprinted genes, placenta-specific genes, immune-related genes, and sperm DNA, which may have a direct or indirect impact on embryo implantation, growth, and development. Moreover, the distinct immunological tolerogenic milieu established at the interface between the mother and fetus plays a crucial role in sustaining pregnancy. Given this, there has been a great deal of interest in the regulation of DNA methylation and alterations in the cellular components of the maternal-fetal immunological milieu. The research on DNA methylation's role in RPL incidence and the control of the mother-fetal immunological milieu is summed up in this review.

Recent investigations have underscored the epigenetic modulation of the immune response; however, the interplay between RNA N6-methyladenosine (m6A) modification and immunomodulation in head and neck squamous cell carcinoma (HNSC) remains relatively unexplored. To bridge this knowledge gap, we undertook an extensive examination of the potential contributions of m6A modification and immunomodulation in HNSC. We amalgamated and deduplicated 27 m6A -related genes (m6AGs) and 1342 immune regulation-related genes (IMRGs), resulting in a comprehensive dataset encompassing 1358 genes. This dataset was scrutinized for m6A modification and immunomodulatory patterns within HNSC specimens. Employing Cox regression analysis and the Least Absolute Shrinkage and Selection Operator (LASSO) technique, we developed a prognostic risk model for m6A regulator-mediated methylation modification and immunomodulation-related differentially expressed genes (m6A&IMRDEGs). Our differential expression analysis delineated 29 m6A&IMRDEGs, and Weighted Gene Co-expression Network Analysis (WGCNA) elucidated two module genes (IL11 and MMP13) subjected to correlation analysis. The prognostic prediction models revealed that the clinical predictive efficacy peaked for 1-year forecasts, followed sequentially by 3-year and 5-year predictions. The risk scores derived from the model adeptly categorized HNSC patients into high- and low-risk cohorts, with the high-risk group exhibiting a more unfavorable prognosis. Protein-Protein Interaction (PPI) analysis identified 7 hub genes implicated in m6A and immune regulation, namely BPIFB1, BPIFB2, GP2, MUC5B, MUC7, PIP, and SCGB3A1. Furthermore, we noted marked disparities in the expression profiles of 18 immune cell types between the high- and low-risk groups. Our results substantiate that the clustering subpopulations and risk models associated with m6A and immune regulatory genes portend a poor prognosis in HNSC. The risk score emerges as a potent prognostic biomarker and predictive metric for HNSC patients. A thorough assessment of m6A and immune regulatory genes in HNSC will augment our comprehension of the tumor immune microenvironment and facilitate the advancement of HNSC therapeutics.

Trehalase plays an important role in insect metabolism and development by hydrolyzing blood sugar trehalose, but it seems to perform primarily an immunomodulatory function in crustaceans whose blood sugar is glucose. Metal ions as pollutants seriously affecting crustacean health, but studies on trehalase in metal immunity are still limited. In this study, a soluble trehalase (NdTre1) that could bind to multiple metals was identified from Neocaridina denticulata sinensis for investigating metal resistance. Expression profiling revealed that NdTre1 was mainly expressed in the gill and was significantly decreased following stimulation with copper (Cu²⁺) and cadmium (Cd²⁺). Transcriptomic analysis of gills revealed an increase in ecdysone synthesis after interference with NdTre1. Increased ecdysone activated the endogenous mitochondrial pathway and the mitogen activated protein kinase (MAPK) pathway to further induced apoptosis. In vitro, Escherichia coli overexpressing recombinant NdTre1 had higher survival and faster growth rates to better adapted the metal-containing medium. Overall, NdTre1 exercises an important immune function in shrimp resistance to metal stimulation by regulating apoptosis and molting. Further investigation can further explore specific response mechanisms of NdTre1 to multiple metals.

Sjögren's syndrome (SS) is a chronic autoimmune disease affecting the exocrine glands and can lead to various systemic symptoms impacting multiple organs. Despite its common occurrence, treatment options for SS have been largely limited, primarily focusing on alleviating symptoms rather than addressing the underlying autoimmune causes. A shift towards personalized medicine leads to the development of new therapeutic strategies aimed at targeting specific molecular pathways implicated in SS. Innovations in biologics are paving the way for inhibiting particular cytokines or cell surface molecules directly involved in the autoimmune mechanism. Furthermore, advancements in regenerative medicine, including the promising field of stem cell therapy, offer the potential for restoring or replacing the impaired salivary and lacrimal glands, providing hope for a more permanent resolution to this condition. This review encompasses cutting-edge treatment strategies for SS, spanning clinical and preclinical drugs to the latest treatment technology. Such advancements promise to drive targeted therapy development and inspire innovative ideas for treatment paradigms in SS.

Trichloroethylene (TCE) is a common environmental contaminant that can induce occupational dermatitis medicamentosa-like TCE (ODMLT), where the liver damage is the most common complication. The study aims to uncover the underlying mechanism of TCE-sensitization-induced liver damage by targeting specific exosomal microRNAs (miRNAs). Among the enriched serum exosomal miRNAs of ODMLT patients, miR-205–5p had a significant correlation coefficient with the liver function damage indicators. Moreover, retinoic acid receptor-related orphan receptor α (RORα) was identified as a direct target of miR-205–5p via specific binding. Further experiments showed that kupffer cells (KCs) underwent M1 phenotypic and functional changes in liver injury induced by TCE which were alleviated by reducing the expression of miR-205–5p. However, this alleviation was reversed by the RORα antagonist SR1001. In vitro experiments showed that miR-205–5p promoted M1 polarization of macrophages and enhanced the secretion of inflammatory factors by regulating RORα. An increase in RORα reversed the polarization direction of M1-type macrophages and reduced the secretion of proinflammatory factors. In addition, pretreatment of mice with SR1078, a specific RORα agonist, effectively blocked M1 polarization of KCs and reduced the severity of TCE-induced liver injury. Our study uncovers that miR-205–5p regulates KC M1 polarization by targeting RORα in immune liver injury induced by TCE sensitization, providing new insight into the molecular mechanisms and new therapeutic targets for ODMLT.

Background: Postmenopausal osteoporosis (PMOP) represents as a significant health concern, particularly as the population ages. Currently, there is a paucity of comprehensive descriptions regarding the immunoregulatory mechanisms and early diagnostic biomarkers associated with PMOP. This study aims to examine immune-related differentially expressed genes (IR-DEGs) in the peripheral blood mononuclear cells of PMOP patients to identify immunological patterns and diagnostic biomarkers. Methods: The GSE56815 dataset from the Gene Expression Omnibus (GEO) database was used as the training group, while the GSE2208 dataset served as the validation group. Initially, differential expression analysis was conducted after data integration to identify IR-DEGs in the peripheral blood mononuclear cells of PMOP. Subsequently, feature selection of these IR-DEGs was performed using RF, SVM-RFE, and LASSO regression models. Additionally, the expression of IR-DEGs in distinct bone marrow cell subtypes was analyzed using single-cell RNA sequencing (scRNA-seq) datasets, allowing the identification of cellular communication patterns within various cell subgroups. Finally, molecular subtypes and diagnostic models for PMOP were constructed based on these selected IR-DEGs. Furthermore, the expression levels of characteristic IR-DEGs were examined in rat osteoporosis (OP) models. Results: Using machine learning, six IR-DEGs (JUN, HMOX1, CYSLTR2, TNFSF8, IL1R2, and SSTR5) were identified. Subsequently, two molecular subtypes of PMOP (subtype 1 and subtype 2) were established, with subtype 1 exhibiting a higher proportion of M1 macrophage infiltration. Analysis of the scRNA-seq dataset revealed 11 distinct cell clusters. It was noted that JUN was significantly overexpressed in M1 macrophages, while HMOX1 showed a marked elevation in endothelial cells and M2 macrophages. Cell communication results suggested that the PMOP microenvironment features increased interactions among M2 macrophages, CD8+ T cells, Tregs, and fibroblasts. The diagnostic model based on these six IR-DEGs demonstrated excellent diagnostic performance (AUC = 0.927). In the OP rat model, the expression of IL1R2 and TNFSF8 were significantly elevated. Conclusion: JUN, HMOX1, CYSLTR2, TNFSF8, IL1R2, and SSTR5 may serve as promising molecular targets for diagnosing and subtyping patients with PMOP. These results offer novel perspectives on the early diagnosis of PMOP and the advancement of personalized immune-based therapies.

Sjögren's syndrome (SS) is a chronic autoimmune disease that affects the exocrine glands and may lead to a range of systemic symptoms that impact various organs. Both innate and adaptive immune pathways might trigger the disease. Studying the signaling pathways underlying SS is crucial for enhancing diagnostic and therapeutic effectiveness. SS poses an ongoing challenge for medical professionals owing to the limited therapeutic options available. This review offers a comprehensive understanding of the intricate nature of SS, encompassing disease classification criteria, risk factors, and signaling pathways in immunity and inflammation. The advancements summarized herein have the potential to spark new avenues of research into SS.

The regulation of the immune system and the occurrence of inflammation are vital factors in the pathophysiology of ischemic stroke. This study aims to screen target molecules which play key roles in alleviating the brain injury following ischemic stroke via regulating neuroinflammation. Several bioinformatics methods were used to identify immune-related genes in ischemic stroke. A total of 218 genes were identified as differentially expressed genes within the GSE97537 dataset. By performing GO, KEGG, and GSEA analyses, DEGs were mainly enriched in pathways related to immunity and inflammation. By utilizing the MCODE plugin in conjunction with Cytoscape software, a total of six crucial genes were identified, including C1qb, C1qc, Fcer1g, Fcgr3a, Tyrobp, and CD14. Based on the above crucial genes, 13 miRNAs were predicted. Furthermore, 71 potential drugs with therapeutic properties that target the crucial genes were screened, including lovastatin, ASPIRIN, and PREDNISOLONE. Moreover, the results of RT-qPCR showed that compared with Sham group, the expressions of C1qb, C1qc, Fcer1g, Fcgr3a, Tyrobp, and CD14 in MCAO group were significantly increased, which was consistent with the expression trend of validation dataset and training dataset. In conclusion, immune-related genes may play a key role in ischemic stroke. In addition, six crucial genes were identified as potential biomarkers and 71 promising drugs were screened to treat ischemic stroke patients.

This study evaluated the effects of Clostridium butyricum supplementation on rumen fermentation, serum immunoglobulins, and fecal microbiota in dairy calves. Seventy-five 3-days-age calves were divided into five groups (n = 15 per group) receiving 0, 0.2, 0.4, 0.8, and 1.6 g/day of C. butyricum freeze-dried powder (10^10 CFU/g) in milk replacer. Rumen fluid and blood samples were collected at various intervals, and fecal samples from eight calves per group were collected at 3, 28, and 42 days. C. butyricum supplementation showed a negative correlation with rumen pH (P = 0.032) and positive correlations with acetate/propionate (P = 0.007) and acetate + butyrate/propionate (P = 0.022). It had quadratic effects on rumen acetate (P = 0.029) and isobutyrate (P = 0.021). IgA concentration increased with dose (P = 0.002), and dose-time interactions affected serum IgM (P = 0.013) and IgG (P

Jatropha curcas is an oil producing seed with high nutritional qualities for consumption. However, due to inherent anti-nutritional factors, appropriate processing is necessary to improve its nutrients utilization. This study was aimed at processing J. curcas using solvent-extraction method and evaluating its inclusion effects in the diet for Clarias gariepinus on its growth status. J. curcas meal was extracted using 80 % methanol to remove phorbol esters and other anti-nutrients. Thereafter, five iso-nitrogenous diets (40 % crude protein) were formulated containing J. curcas meal replacements of soybeans meal at 0 % (TRT0), 25 % (TRT25), 50 % (TRT50), 75 % (TRT75) and 100 % (TRT100) and fed to C. gariepinus for 70 days. Results showed that TRT25 fish had the highest mean weight gain and specific growth. The serum alkaline phosphate, alanine aminotransferase, and aspartate aminotransferase levels began to rise significantly (p ≤ 0.05) at 50 % replacement. Likewise, the assessment of gut ecology and morphology indicated that TRT25 had significantly (p ≤ 0.05) the highest gut bacteria colony forming unit (2.60 ×104±0.02cfu/g) and most favorable area of absorption (0.16±0.01 cm2). The histopathological observation of the fish intestine, liver and gills indicated no visible deformity in TRT0 and TRT25 fish. However, various degrees of degenerations were observed in the fish fed with 50 % and higher inclusion of J. curcas. This study showed that methanol-extracted J. curcas meal can be effectively utilized for C. gariepinus at 25 % of replacement.

Insect meal inclusion in aquaculture feed has received increased interest as a sustainable alternative to fishmeal and recent evidence has shown additional effects on modulating the immune response. However, lack of effects of insect meal on fish immunity in a few studies have put these beneficial effects into question. The objective of this meta-analysis was to summarize the effects of fishmeal replacement with insect meal on the innate immune response of several fish species based on differential gene expression via qPCR. A systematic literature search was conducted using online databases including Web of Science and ScienceDirect that found 197 studies as of August 2023, however only 20 studies met the criteria of high-quality studies focused on the immune response of fish and were included in this meta-analysis. The most studied insect meal was from black soldier fly, followed by yellow mealworm, and the most commonly analyzed tissue was the liver, followed by the intestine. The effect of fishmeal replacement with insect meal on fish immune responses were examined using a mixed model, with study as the random effect. This meta-analysis found a non-linear (quadratic) relationship (P = 0.017) between immune gene expression fold change and the level of fishmeal replacement with insect meal. Based on the fitted quadratic curve, a 40 % replacement of fishmeal with insect meal resulted in the highest upregulated immune response in fish. Fish taxonomic family was also found to have an effect (P = 0.004) on immune gene expression, where the taxonomic family Moronidae was more affected, with an average fold change of 2.783 (± 0.325). Other variables examined, including the insect type, tissue analyzed, dietary crude protein level, did not affect the immune response (P > 0.05). This meta-analysis also found that dietary lipid had a significant correlation with immune gene expression, and should be taken into consideration in future studies and meta-analyses. These findings are impactful since they provide evidence for the optimal dietary replacement level of insect meals required to significantly affect the innate immune response across several fish species.

The research on the mechanism of nephrolithiasis formation is of great importance due to the fact that the high incidence and recurrence rate of nephrolithiasis bring considerable economic burdens to patients and society. As an important component in the nephrolithiasis formation process, the immune-inflammatory process has been gradually valued by researchers in recent years. In this study, articles related to the immune-inflammatory process of nephrolithiasis published since 2000 were retrieved based on the Web of Science (WoS) database. Eventually, a total of 370 articles were selected for subsequent analyses. Besides, VOSviewer, CiteSpace, and Bibliometrix were employed to quantitatively analyze and visualize the data. The number of articles related to the immune-inflammatory process of nephrolithiasis has increased rapidly in the last five years. From the country level, most articles were contributed by China (n = 140) and the United States (n = 99) contributed the most documents. From the institution level, University of Florida (n = 36) and Nagoya City University (n = 21) had the most articles. From the journal level, Journal of Urology and Urolithiasis published the most articles in this field. Keywords mainly included inflammation, oxidative stress, calcium oxalate, osteopontin, and hyperoxaluria, which represented the research directions in this field. The most productive author was Khan SR (n = 33), whose articles obtained the highest number of citations (2086 times). These efforts may help researchers understand the current progress and status of research on the immune-inflammatory process of nephrolithiasis and identify future research hotspots and directions.

This study was conducted to investigate the effects of puerarin on growth, digestive enzymes, antioxidant capacity, immunity and liver health of Acanthopagrus latus. Four diets were formulated: a control diet (C) and C supplemented with 200, 400, and 600 mg/kg puerarin (CP2, CP4, and CP6, respectively) and a eight-week feeding trial was conducted of fish. The results showed that the addition of 400 mg/kg puerarin significantly increased weight gain (WG), specific growth rate (SGR), and decreased the feed conversion ratio (FCR) compared to C group. Dietary supplementation with 600 mg/kg puerarin significantly increased lipase (LPS) activity compared to the C group. The addition of 200 mg/kg puerarin significantly reduced low-density lipoprotein cholesterol (LDL-C) and 400 mg/kg puerarin significantly reduced total cholesterol (T-CHO), triglycerides (TG) and HDL-C compared to the C group. Dietary supplementation with 400 mg/kg puerarin significantly increased serum and liver glutathione (GSH) activity and decreased malondialdehyde (MDA) content compared to the C group. Addition of 400 mg/kg puerarin significantly increased liver catalase (CAT) activity compared to the C group. Supplementation of 600 mg/kg and 400 mg/kg of puerarin significantly increased serum alkaline phosphatase (AKP) and lysozyme (LZM) activities, respectively. Compared to the C group, the addition of 200 mg/kg of puerarin significantly increased the activities of acid phosphatase (ACP) and alkaline phosphatase (AKP) in the liver. CP4-feeding significantly upregulated the expression of nrf2, ho-1, and gclc while downregulating the expression of keap1 compared to the C group. The addition of puerarin significantly reduced the expression of tnf-α and il-6 compared to the C group. Supplementation of 200 mg/kg puerarin significantly reduced the expression of bax compared to the C group. In conclusion, dietary supplementation with puerarin had positive effects on the growth, digestive enzymes, antioxidant capacity, immunity, and liver health of fish, particularly at 503.5 mg/kg.

Background: Benign paroxysmal positional vertigo (BPPV) is a common neurological disorder with a high recurrence rate. Type 2 diabetes mellitus (T2DM) is recognized as a risk factor for BPPV recurrence. However, the genomic association between T2DM and BPPV recurrence remains understudied. Methods: Differential gene expression analysis and weighted gene co-expression network analysis were used to identify shared genes between BPPV recurrence and T2DM. The MCC algorithm was employed to select hub genes from the protein-protein interaction network of the shared genes. The predictive efficacy of hub genes for BPPV recurrence and T2DM was assessed using ROC curve analysis. Genemania database was used to identify downstream targets of hub genes. The immune infiltration landscape of BPPV and T2DM was characterized using the CIBERSORT algorithm. Correlation analysis was performed to explore the relationship between hub genes and immune cells. The expression levels of hub genes in patient blood samples were validated using qPCR. Results: Thirteen shared genes were identified and a protein-protein interaction network was constructed for BPPV recurrence and T2DM. Subsequently, four hub genes were selected, and their expression levels effectively predicted the occurrence of BPPV recurrence and T2DM. These hub genes were highly correlated with immune cell infiltration, indicating a common mechanism underlying recurrent BPPV and T2DM. Finally, the upregulation of hub genes in patients with T2DM comorbid with BPPV recurrence was confirmed in blood samples. These hub genes may serve as predictive biomarkers for assessing the recurrence rate in BPPV patients with comorbid T2DM. Conclusion: We proposed shared gene characteristics between BPPV recurrence and T2DM, revealing an immune-mediated inflammatory regulation as a common pathway and identifying four immune-related biomarkers and potential therapeutic targets for T2DM comorbid with recurrent BPPV.

The interaction between the immune system and the tumor matrix has a huge impact on the progression and treatment of cancer. This paper summarizes and discusses the crosstalk between T cells and cancer-associated fibroblasts (CAFs). CAFs can also produce inhibitors that counteract the function of T cells and promote tumor immune escape, while T cells can also engage in complex two-way interactions with CAFs through direct cell contact, the exchange of soluble factors such as cytokines, and the remodeling of the extracellular matrix. Precise targeted intervention can effectively reverse tumor-promoting crosstalk between T cells and CAFs, improve anti-tumor immune response, and provide a new perspective for cancer treatment. Therefore, it is important to deeply understand the mechanism of crosstalk between T cells and CAFs. This review aims to outline the underlying mechanisms of these interactions and discuss potential therapeutic strategies that may become fundamental tools in the treatment of cancer, especially hard-to-cure cancers.

Background: Inflammation and immune factors are the core of intervertebral disc degeneration (IDD), but the immune environment and epigenetic regulation process of IDD remain unclear. This study aims to identify immune-related diagnostic candidate genes for IDD, and search for potential pathogenesis and therapeutic targets for IDD. Methods: Gene expression datasets were obtained from the Gene Expression Omnibus (GEO). Differential expression immune genes (Imm-DEGs) were identified through weighted gene correlation network analysis (WGCNA) and linear models for microarray data analysis (Limma). LASSO algorithm was used to identify feature genes related to IDD, which were compared with core node genes in PPI network to obtain hub genes. Based on the coefficients of hub genes, a risk model was constructed, and the diagnostic value of hub genes was further evaluated through receiver operating characteristic (ROC) analysis. Xcell, an immunocyte analysis tool, was used to estimate the infiltration of immune cells. Finally, nucleus pulposus cells were co-cultured with macrophages to create an M1 macrophage immune inflammatory environment, and the changes of hub genes were verified. Results: Combined with the results of WGCNA and Limma gene differential analysis, a total of 30 Imm-DEGs were identified. Imm-DEGs enriched in multiple pathways related to immunity and inflammation. LASSO algorithm identified 10 feature genes from Imm-DEGs that significantly affected IDD, and after comparison with core node genes in the PPI network of Imm-DEGs, 6 hub genes (NR1H3, SORT1, PTGDS, AGT, IRF1, TGFB2) were determined. Results of ROC curves and external dataset validation showed that the risk model constructed with the 6 hub genes had high diagnostic value for IDD. Immunocyte infiltration analysis showed the presence of various dysregulated immune cells in the degenerative nucleus pulposus tissue. In vitro experimental results showed that the gene expression of NR1H3, SORT1, PTGDS, IRF1, and TGFB2 in nucleus pulposus cells in the immune inflammatory environment was up-regulated, but the change of AGT was not significant. Conclusions: The hub genes NR1H3, SORT1, PTGDS, IRF1, and TGFB2 can be used as immunorelated biomarkers for IDD, and may be potential targets for immune regulation therapy for IDD.

Objective: Ulcerative Colitis (UC) manifests as a chronic inflammatory condition of the intestines, marked by ongoing immune system dysregulation. Disulfidptosis, a newly identified cell death mechanism, is intimately linked to the onset and advancement of inflammation. However, the role of disulfidptosis in UC remains unclear. Methods: We screened differentially expressed genes (DEGs) associated with disulfidptosis in multiple UC datasets, narrowed down the target gene number using lasso regression, and conducted immune infiltration analysis and constructed a clinical diagnostic model. Additionally, we explored the association between disulfidptosis-related key genes and disease remission in UC patients receiving biologic therapy. Finally, we confirmed the expression of key genes in FHC cells and UC tissue samples. Results: In the differential analysis, we identified 20 DEGs associated with disulfidptosis. Immune infiltration results revealed that five genes (PDLIM1, SLC7A11, MYH10, NUBPL, OXSM) exhibited strong correlations with immune cells and pathways. Using GO, KEGG and WGCNA analyses, we discovered that gene modules highly correlated with disulfidptosis-related gene expression were significantly enriched in inflammation-related pathways. Additionally, we developed a nomogram based on these five immune-related disulfidptosis genes for UC diagnosis, showing robust diagnostic capability and clinical efficacy. Kaplan-Meier survival analysis revealed a significant link between changes in the expression levels of these cell genes and disease remission in UC patients receiving biologic therapy. In line with previous studies, similar expression changes of the target gene were seen in both UC cell models and tissue samples. Conclusions: This study utilized bioinformatic analysis and machine learning to identify and analyze features associated with disulfidptosis in multiple UC datasets. This enhances our comprehension of the role disulfidptosis plays in intestinal immunity and inflammation in UC, providing new perspectives for developing innovative treatments for UC.

Shezhi Huangling Decoction (SHD) has been proven clinically effective in regulating metabolic and immune homeostasis in the treatment of glioma. The investigation aimed to deconstruct the active constituents and mechanisms of SHD. Effects of SHD on malignant characteristics of HS683 and KNS89 cells have been investigated by CCK-8, clone formation, flow cytometry, and Transwell assays. A mouse xenograft model was established to assess the effect of SHD or SHD + temozolomide (TMZ) in vivo. A total of 461 constituents were found from SHD in UPLC/Q-TOF-MS/MS analysis. Functional enrichment analysis showed that pathway in cancer, proteoglycans in cancer, regulation of epithelial cell proliferation, inflammation/immune, gliogenesis, brain development, cell adhesion, and autophagy could participate in the treatment of SHD. Additionally, 9 hub genes (AKT1, TP53, CTNNB1, STAT3, EGFR, VEGFA, PIK3CA, ERBB2, and HIF1A) were identified as hub genes. Moreover, we found that SHD may greatly reduce the migration and accelerate apoptosis of HS683 and KNS89 cells. Additionally, SHD coordinates TMZ to restrict tumor growth were found in the mice. Our results suggest that the malignant behaviors of glioma cells are suppressed by SHD and the mechanism may be closing on the inhibition of the PI3K/Akt-HIF1A axis. SHD may serve as a synergistic therapeutic choice for TMZ to suppress glioblastoma growth.

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system with progressive lifelong disability. Current treatments are particularly effective at the early inflammatory stage of the disease but associate with safety concerns such as increased risk of infection. While clinical and epidemiological evidence strongly support the role of a bidirectional communication between the lung and the brain in MS in influencing disease risk and severity, the exact processes underlying such relationship appear complex and not fully understood. This short review aims to summarize key findings and future perspectives that might provide new insights into the mechanisms underpinning the lung-brain axis in MS.

With the purpose of identifying a sensitive, robust, and easy-to-measure set of biomarkers to assess stress reactivity, we here study a large set of relatively easy to obtain markers reflecting subjective, autonomic nervous system (ANS), endocrine, and inflammatory responses to acute social stress (n = 101). A subset of the participants was exposed to another social stressor the next day (n = 48) while being measured in the same way. Acute social stress was induced following standardized procedures. The markers investigated were self-reported positive and negative affect, heart rate, electrodermal activity, salivary cortisol, and ten inflammatory markers both in capillary plasma and salivary samples, including IL-22 which has not been studied in response to acute stress in humans before. Robust effects (significant effect in the same direction for both days) were found for self-reported negative affect, heart rate, electrodermal activity, plasma IL-5, plasma IL-22, salivary IL-8 and salivary IL-10. Of these seven markers, the participants’ IL-22 responses on the first day were positively correlated to those on the second day. We found no correlations between salivary and capillary plasma stress responses for any of the ten cytokines and somewhat unexpectedly, cytokine responses in saliva seemed more pronounced and more in line with previous literature than cytokines in capillary plasma. In sum, seven robust and easy to obtain biomarkers to measure acute stress response were identified and should be used in future stress research to detect and examine stress reactivity. This includes IL-22 in plasma as a promising novel marker.

A 60-day feeding trial was conducted to investigate the effects of dietary a Chinese herbal compound (CHC) including Pulsatillae Radix, Coptidis Rhizoma, Cortex Phellodendri Amurensis and Fraxini Cortex on the growth performance, intestinal and liver histology, antioxidative capacity and immunity of juvenile large yellow croaker (Larimichthys crocea) with the initial body weight of 17.00 ± 0.03 g. Four experimental diets were formulated to contain 0 mg/kg (CHC0), 250 mg/kg (CHC250), 500 mg/kg (CHC500), and 750 mg/kg (CHC750) of CHC, respectively. Results showed that dietary CHC did not significantly affect the survival of large yellow croaker (P > 0.05). Compared with the control, the CHC500 group showed higher weight gain and protein efficiency ratio, along with a lower feed conversion ratio (P < 0.05). Furthermore, increasing levels of dietary CHC linearly decreased the activities of aspartate aminotransferase and alanine aminotransferase, and malondialdehyde content in serum. Moreover, dietary CHC significantly increased the total antioxidative capacity and complement levels in serum (P < 0.05). The relative expressions of sod1, nrf2, il-10 and tnf-α in liver and intestine were upregulated in the CHC500 group (P < 0.05). Additionally, the activities of digestive and absorptive enzymes in intestine were significantly increased in the CHC500 group (P < 0.05). The length of intestinal villus height, villus width and perimeter ratio were higher in the CHC supplemented diets. In conclusion, CHC supplementation in diet could improve growth performance, anti-oxidative capacity and immunity of large yellow croaker.

The intestine serves as the primary defense mechanism safeguarding fish body against pathogen infiltration. Unlike cyprinid and salmonid fish, sturgeon features a distinctive special spiral valve structure within their intestines. Several studies propose that dietary lipid intake may impact the intestinal barrier function of fish. The presence of this influence within the special spiral valve intestine of sturgeon currently remains unresolved. This study aimed to explore the effects of a low or high-lipid diet on morphology, tight junction, antioxidant and immune performance, and intestinal microbiota in the spiral valve intestine of Siberian sturgeon (Acipenser baerii) (14.19 ± 0.07 g). Three diets with different lipid levels of 8.87 % (low lipid, LL), 16.93 % (moderate lipid, ML), and 24.88 % (high lipid, HL) were designed for a 70-day feeding experiment. Histological analysis revealed that the LL diet induced chronic proliferative inflammation and intestinal mucosa adhesion. In addition, the LL diet reduced the height of mucosal fold and microvilli while the HL diet shortened the microvilli only. The expression of claudin1 was inhibited by the LL diet while Claudin2 was stimulated by the HL diet. Both LL and HL diets suppressed the expression of occludin. Superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (T-AOC) of spiral valve intestine were not sensitive to different lipid levels, but glutathione peroxidase (GSH-Px) was decreased in fish fed with the LL, and malonaldehyde (MDA) was increased in fish fed with the HL. The sturgeons fed with LL diet had declined immunoglobulin M (IgM), IgG, tumor necrosis factor α (TNFα), interleukin 1β (IL1β), IL10, and transforming growth factor β1 (TGFβ1), while HL diet had no significant effects on them. With the increase of lipid levels, the alpha diversity of spiral valve intestinal microbiota showed a downward trend. The dominant genera were mainly clostridium_sensu_stricto_1, Bacillus, Mycoplasma, and the HL group also included Lactococcus. Fourteen differentially abundant taxa were identified by LEfSe analysis, which could be biomarkers. In conclusion, a low-lipid (8.87 %) diet damaged the mechanical barrier and reduced antioxidant and immune performance. High-lipid (24.88 %) diet decreased the height of microvilli and negatively affected tight junction proteins and intestinal microbiota.

Background: Oral lichen planus (OLP) is a common chronic oral mucosal disease with 1.4 % malignant transformation rate, and its etiology especially immune pathogenesis remains unclear. This study was aimed at investigating the immune cells related molecular underlying the pathophysiology of OLP through bioinformatics analysis. Methods: The dataset GSE52130 obtained from the Gene Expression Omnibus (GEO) database was conducted a comprehensive analysis in this study. The CIBERSORTx was used for investigating immune cells infiltration. The gene set enrichment analysis (GSEA) and gene ontology (GO) enrichment were performed for exploring the biological functions and gene annotation. The protein-protein interactions (PPI) were constructed by STRING database and visualized by Cytoscape software. The cytohubba plugin was utilized for screening hub genes. The receiver operating characteristic (ROC) was performed for evaluating diagnostic value of hub genes. The miRNAs, lncRNAs and drugs were respectively predicted by NetworkAnalyst, miRTarbase, ENCORI, and DGIdb database. Results: This study identified 595 differentially expressed genes (DEGs). The GSEA indicated keratinization, innate immune system and biological oxidation were involved in OLP. GO analysis showed extracellular matrix and keratinocyte were mainly enriched. And we found the activated memory CD4+ T cells were lowly infiltrated in OLP. We identified 101 activated memory CD4+ T-cells-related DEGs. Three hub genes (APP, IL1B, TF) were selected. APP and IL1B were significantly up-regulated, whereas TF was down-regulated in OLP. The three hub genes show high diagnostic value in OLP. Additionally, they were involved in MAPK signal, NF-kappaB signal and iron metabolism in OLP. What's more, NEAT1/XIST - miR - 15a - 5p/miR - 155–5p - APP/IL1B signal axis was focused in competing endogenous RNA (ceRNA) network. In addition, 35 drugs were predicted for OLP. Conclusion: Three activated memory CD4+ T-cells-related DEGs were identified by integrative analysis. It may provide novel insight into the pathogenesis of OLP and suggest potential therapeutic targets for OLP.

Background: Numerous studies have shown a strong correlation between disulfidptosis and various cancers. However, the expression and function of RPN1, a crucial gene in disulfidptosis, remain unclear in the context of cancer. Methods: Gene expression and clinical information on lung adenocarcinoma were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. RPN1 expression was analyzed using the Timer2.0 and the Human Protein Atlas (HPA) databases. Prognostic significance was assessed using Cox regression analysis and Kaplan–Meier curves. Genetic mutations and methylation levels were examined using the cBioPortal and UALCAN platforms, respectively. The relationship between RPN1 and tumor mutation burden (TMB) and microsatellite instability (MSI) across different cancer types was analyzed using the Spearman correlation coefficient. The relationship between RPN1 and immune cell infiltration was analyzed using the Timer2.0 database, whereas variations in drug sensitivity were explored using the CellMiner database. Receiver operating characteristic curves validated RPN1’s diagnostic potential in glioma, and its correlation with immune checkpoint inhibitors (ICIs) was assessed using Spearman’s correlation coefficient. Single-sample gene set enrichment analysis elucidated a link between RPN1 and immune cells and pathways. In addition, a nomogram based on RPN1 was developed to predict patient prognosis. The functional impact of RPN1 on glioma cells was confirmed using scratch and Transwell assays. Result: RPN1 was aberrantly expressed in various cancers and affected patient prognosis. The main mutation type of RPN1 in the cancer was amplified. RPN1 exhibited a positive correlation with myeloid-derived suppressor cells, neutrophils, and macrophages, and a negative correlation with CD8+ T cells and hematopoietic stem cells. RPN1 expression was associated with TMB and MSI in various cancers. The expression of RPN1 affected drug sensitivity in cancer cells. RPN1 was positively correlated with multiple ICIs in gliomas. RPN1 also affected immune cell infiltration into the tumor microenvironment. RPN1 was an independent prognostic factor for gliomas, and the nomogram demonstrated excellent predictive performance. Interference with RPN1 expression reduces the migratory and invasive ability of glioma cells. Conclusion: RPN1 exerts multifaceted effects on different stages of cancer, including immune infiltration, prognosis, and treatment outcomes. RPN1 expression affects the prognosis and immune microenvironment infiltration in patients with glioma, making RPN1 a potential target for the treatment of glioma.

ABSTRACT: Three hundred one-day-old Avian 48 broiler chicks were used to investigate the effect of lignocellulose (LC) and probiotic supplementation in broiler chicken diet on growth performance, digestive health, litter quality, and some gene expression. Experimental treatments consisted of 3 × 2 factorial arrangements with 3 levels of LC without or with probiotics to formulate 6 experimental groups. Groups 1, 2, and 3 were fed on the basal diet with dietary LC inclusion at 0, 0.5, and 1.0%, respectively, while groups 4, 5, and 6 were fed on the previously mentioned design with Bacillus subtilis at 100 gm/ton. The results revealed that Dietary LC inclusion nonsignificantly (P ≥ 0.05) reduced body weight (BW), body weight gain (BWG), and feed intake. Meanwhile, B. subtilis supplementation improved BW and BWG and enhanced the effect of LC on the broilers' weight. The group fed a 0.5% LC and B. subtilis-supplemented diet recorded the best (P ≥ 0.05) BW, BWG, FCR, PER, EEU, and PI. LC and or B. subtilis supplementation improved carcass traits of broiler (higher dressing% with lower abdominal fat% compared with a control group), intestinal health, and absorptive capacity. LC potentiates the effect of B. subtilis supplementation in broilers' diet in modulating intestinal microflora (lowered (P ≥ 0.05) cecal Coliform and increased Lactobacillus counts), the highest Coliform counts were recorded in group fed 0.5 or 1.0% LC plus B. subtilis. LC at 0.5 or 1.0% and or B. subtilis supplementation reduced (P ≥ 0.05) litter moisture% at the 2nd, 4th, and 6th wk compared to the control group. Dietary inclusion of LC and or B. subtilis supplementation significantly (P < 0.001) up-regulated hepatic growth-related genes (growth hormone receptor (GHR) and insulin growth factor1 (IGF-1)) and antioxidant-related genes (superoxide dismutase 1 (SOD1), glutathione peroxidase (GPX1) and uncoupling protein (UCP) and down-regulated (P < 0.001) splenic toll-like receptor 4 (TLRP) gene expression while had no significant effect on splenic interleukin 8 (IL8) and tumor necrosis factor (TNF) with the best-obtained results with 1.0% followed by 0.5% LC with B. subtilis supplementation. We concluded that dietary LC and/or B. subtilis supplementation positively affected the growth performance, feed efficiency, carcass quality, intestinal absorptive capacity and health, litter quality and growth, and antioxidant and immune-related gene expression.

ABSTRACT: Avian leukosis virus Subgroup J (ALV-J) exhibits high morbidity and pathogenicity, affecting approximately 20% of poultry farms. It induces neoplastic diseases and immunosuppression. Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1), a proapoptotic mitochondrial protein in the B-cell lymphoma-2 (Bcl-2) family, plays a role in apoptosis in cancer cells. However, the connection between the PMAIP1 gene and ALV-J pathogenicity remains unexplored. This study investigates the potential impact of the PMAIP1 gene on ALV-J replication and its regulatory mechanisms. Initially, we examined PMAIP1 expression using quantitative real-time PCR (qRT-PCR) in vitro and in vivo. Furthermore, we manipulated PMAIP1 expression in chicken fibroblast cells (DF-1) and assessed its effects on ALV-J infection through qRT-PCR, immunofluorescence assay (IFA), and western blotting (WB). Our findings reveal a significant down-regulation of PMAIP1 in the spleen, lung, and kidney, coupled with an up-regulation in the bursa and liver of ALV-J infected chickens compared to uninfected ones. Additionally, DF-1 cells infected with ALV-J displayed a notable up-regulation of PMAIP1 at 6, 12, 24, 48, 74, and 108 h. Over-expression of PMAIP1 enhanced ALV-J replication, interferon expression, and proinflammatory factors. Conversely, interference led to contrasting results. Furthermore, we observed that PMAIP1 promotes virus replication by modulating mitochondrial function. In conclusion, the PMAIP1 gene facilitates virus replication by regulating mitochondrial function, thereby enriching our understanding of mitochondria-related genes and their involvement in ALV-J infection, offering valuable insights for avian leukosis disease resistance strategies.

Palmatine as a medicinal herbs extract has strong bacteriostatic ability and is a promising source of antibacterial additive. The objective of this study was to assess the feasibility of palmatine as an antibiotic alternative in diet for genetically improved farmed tilapia (GIFT, Oreochromis niloticus). Four experimental diets were formulated with 0, 200, 400, and 800 mg/kg palmatine. Tilapia with consistent size (initial body weight 3.43 ± 0.02 g) were fed the test diets twice daily for ten weeks. Dietary palmatine inclusion regardless of levels unaffected the growth performance and feed efficiency (P > 0.05). However, dietary 200–800 mg/kg palmatine inclusion reduced the levels of total cholesterol and low-density lipoprotein cholesterol as well as the ratios of low-density/high-density lipoprotein cholesterol and aspartate/alanine aminotransferase in serum (P < 0.05), but generally improved the antioxidant-related enzymes activities in intestine, plasma and liver, the immunoglobulin M, complement 3, and complement 4 contents and lysozyme activity in plasma, and the phagocytic activity of macrophages in head kidney. Bacterial challenge test demonstrated that dietary supplementation with 200–800 mg/kg palmatine enhanced the resistance of tilapia to Aeromonas hydrophila, and the relative percentage survival was the highest in fish fed diet with 400 mg/kg palmatine. In conclusion, dietary palmatine supplementation enhanced the antioxidant and innate immune responses as well as the resistance against A. hydrophila without compromising growth performance of tilapia, and the suitable inclusion level of palmatine was 400 mg/kg of diet for tilapia.

Guanidine acetic acid (GAA) is a safe feed additive and the only precursor for the creatine synthesis of vertebrates. Aeromonas hydrophila is a major fish pathogen causing severe morbidity and mortality in the aquaculture sector. Under the current intensive farming system, A feed additive that can improve fish disease resistance is urgently needed. In teleost fish, the spleen (SP) and head kidney (HK) play a crucial role in peripheral immunity organs and fish skin (SK) serves as one of the most important mucosal barriers. Thus, the study focused on immune defense substances, inflammatory process, and mechanisms of molecular action in the HK, SP, and SK of on-growing grass carp (169.46–600.89 g). The fish were fed graded levels of GAA (0, 150, 300, 450 and 600 mg/kg) for 60 days, and then conducted a 14-day challenge experiment by intraperitoneal injection of Aeromonas hydrophila. In our results, we found that 300 or 450 mg/kg GAA could down-regulate the pro-inflammatory cytokines IL-(1β, 6, 12p40 and 17D), TNF-α and IFN-γ2 mRNA expression, and up-regulate the pro-inflammatory cytokines IL-(10, 11 and 4/13 A) and TGF-β1 mRNA expression in the HK, SP and SK. Furthermore, 300 or 450 mg/kg GAA could up-regulate the mRNA expression and promote the protein phosphorylation of STAT3 in the HK, SP and SK. Indicating that in the case of Aeromonas hydrophila. challenge, GAA could enhance the immune defense and mediated the inflammatory process, possibly via the JAKs-STATs signaling pathway in fish.

Background: The clinical significance of immune-related antigen CD58 in gliomas remains uncertain. The aim of this study was to examine the clinical importance and possible core related genes of CD58 in gliomas. Methods: Pan-cancer analysis was to observe the association between CD58 and different tumors, glioma RNA sequencing data and clinical sample analyses were used to observe the relationship between CD58 and glioma, shRNA interference models were to observe the impact of CD58 on glioma cell function, and four glioma datasets and two online analysis platforms were used to explore the core related genes affecting the correlation between CD58 and glioma. Results: High CD58 expression was associated with worse prognosis in various tumors and higher malignancy in glioma. Down regulation of CD58 expression was linked to decreased proliferation, increased apoptosis, and reduced metastasis in glioma cells. The pathways involved in CD58-related effects were enriched for immune cell adhesion and immune factor activation, and the core genes were CASP1, CCL2, IL18, MYD88, PTPRC, and TLR2. The signature of CD58 and its core-related genes showed superior predictive power for glioma prognosis. Conclusion: High CD58 expression is correlated with more malignant glioma types, and also an independent risk factor for mortality in glioma. CD58 and its core-related genes may serve as novel biomarkers for diagnosing and treating glioma.

Immune exhaustion is a state of immune cell dysfunction that occurs most commonly following chronic exposure to an antigen which persists after the immune response fails to remove it. Exhaustion has been studied most thoroughly with several cancers, but has also been observed in several chronic infectious diseases. The topic has mainly been studied with CD8+ T cells, but it can also occur with CD4+ T cells and other immune cell types too. Exhaustion is characterized by a hierarchical loss of effector cell functions, up-regulation of immuno-inhibitory receptors, disruption of metabolic activities, and altered chromatin landscapes. Exhaustion has received minimal attention so far in diseases of veterinary significance and this review's purpose is to describe examples where immune exhaustion is occurring in several bovine disease situations. We also describe methodology to evaluate immune exhaustion as well as the prospects of controlling exhaustion and achieving a more suitable outcome of therapy in some chronic disease scenarios.

Background: Fatty acid oxidation (FAO) is considered to play a vital part in tumor metabolic reprogramming. But the comprehensive description of FAO dysregulation in tumors has not been unknown. Methods: We obtained FAO genes, RNA-seq data and clinical information from the Msigdb, TCGA and GTEx databases. We assessed their prognosis value using univariate cox analysis, survival analysis and Kaplan-Meier curve. We determined the function of FAO genes using gene set variation analysis. The correlation analysis was calculated by corrplot R package. Immunotherapy response was assessed through TIDE scores. The protein expression levels of FAO genes were validated using immunohistochemistry (IHC). Results: The FAO scores were highest in COAD but lowest in PCPG. FAO scores were significantly associated with the prognosis of some cancers in OS, DSS, DFI and PFI. Besides, gene set variation analysis identified that FAO scores were related to immune-related pathways, and immune infiltration analysis showed FAO scores were positively related to cancer-associated fibroblasts and various immune-related genes. TIDE scores were significantly decreased in ACC, CHOL, ESCA, GBM, LAML, SARC, SKCM and THCA compared with normal samples, while it was significantly increased in BLCA, LUAD, LUSC, PCPG, PRAD and STAD. Besides, most FAO genes were downregulated in pan-cancer compared with normal samples. Moreover, we found copy number variation (CNV) of FAO genes played a positive role in their mRNA expression, while methylation was negative. We determined FAO genes were closely related to some drugs in pan-cancer. Conclusions: FAO score is a novel and promising factor for predicting outcomes.

Background: The involvement of molecules associated with PANoptosis in hepatocellular carcinoma (HCC) is still not well understood. Methods: Various R packages were utilized to analyze within the R software. Data that was freely accessible was obtained from the databases of The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). Results: Here, we comprehensively explored the role of PANoptosis-related genes in HCC. The caspase 2 (CASP2) was identified as the interest gene for further analysis. We found that CASP2 is related to the poor prognosis and worse clinical features of HCC patients. Moreover, we explored the biological pathway CASP2 is involved in and found that CASP2 is associated with multiple carcinogenic pathways. Also, we noticed that CASP2 can significantly reshape the HCC immune microenvironment and affect the response rate of immunotherapy. Analysis of drug sensitivity suggested that individuals exhibiting elevated CASP2 levels may display increased susceptibility to doxorubicin and vorinostat while demonstrating resistance towards erlotinib, lapatinib, sunitinib, and temsirolimus. Meanwhile, we explored the single-cell distribution of CASP2 in the HCC microenvironment. To enhance the clinical application of CASP2 in HCC, we constructed a prognosis model using the molecules derived from CASP2, which demonstrated good efficiency in predicting patients prognosis. Moreover, in vitro experiments indicated that CASP2 can significantly inhibits cell proliferation, invasion and migration ability of HCC cells. Conclusions: Our study comprehensively explored the role of PANoptosis-related molecule CASP2 in HCC, which can provide directions for future studies.

Clear cell renal cell carcinoma (ccRCC) is known as the most common type of renal cancer. Recently, a series of advances have been made in targeted therapy for ccRCC. To combat this highly metastatic tumor, novel therapeutic targets still need to be developed. C-type lectins (CLECs) contain a characteristic C-type lectin-like domain and affect several physiological functions. The effects of C-type lectin 2D (CLEC2D) on cancer progression have been revealed in several types of cancers; however, its expression in ccRCC tissues, and the possible effects on the progression and metastasis of ccRCC, are still unclear. Herein, we found the high mRNA and protein levels of CLEC2D in ccRCC tissues. We further found that CLEC2D expression was correlated with the prognosis of ccRCC patients and correlated with the tumor size (p = 0.019*) of patients. In addition, CLEC2D affected tumor immune infiltration, confirmed by the further analysis. CLEC2D knockdown suppressed the proliferation of ccRCC cells in vitro and restrained ccRCC tumor growth and immune infiltration in mice. Therefore, we believe that CLEC2D has the potential to serve as a promising ccRCC therapeutic target.

Background: Ulcerative colitis (UC) is an inflammatory bowel disease characterized by persistent colonic inflammation. Here, we performed a systematic analysis to gain better insights into UC pathogenesis. Methods: We analyzed two UC-related datasets extracted from the gene expression omnibus database using several bioinformatics tools. The primary cell types and key subgroups of primary cells associated with UC and differentially expressed genes (DEGs) between UC and control samples were identified. The molecular regulation of the key genes was also predicted. The gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses of marker genes of key cell subgroups and model genes were performed. The expression of key enriched genes was validated in 10 clinical samples using real-time quantitative polymerase chain reaction (RT-qPCR). Results: Monocytes were identified as the major cell type. Ten differentially expressed marker genes were obtained by intersecting the 3121 DEGs, 38 marker genes in major cell types, and 104 marker genes in key cell subgroups. Four essential genes, associated with immune response, were obtained using support vector machine recursive feature elimination and least absolute shrinkage and selection operator analyses. The four essential genes were highly expressed in Cluster 0 during differentiation. Validation of the four key genes in colonic mucosal biopsy specimens from 10 normal and 10 UC patients revealed that CREM was highly expressed in both the lesion-free sites and lesion sites colonic mucosa of UC patients compared with normal adults. Conclusions: We identified CREM involved in UC pathogenesis, which is expected to provide a new therapeutic target for UC.

Alzheimer's disease (AD) involves a complex pathological process that evolves over years, and its etiology is understood as a classic example of gene-environment interaction. The notion that exposure to microbial organisms may play some role in AD pathology has been proposed and debated for decades. New evidence from model organisms and -omic studies, as well as epidemiological data from the recent COVID-19 pandemic and widespread use of vaccines, offers new insights into the “germ hypothesis” of AD. To review new evidence and identify key research questions, the Duke/University of North Carolina (Duke/UNC) Alzheimer's Disease Research Center hosted a virtual symposium and workshop: “New Approaches for Understanding the Potential Role of Microbes in Alzheimer's disease.” Discussion centered around the antimicrobial protection hypothesis of amyloid accumulation, and other mechanisms by which microbes could influence AD pathology including immune cell activation, changes in blood-brain barrier, or direct neurotoxicity. This summary of proceedings reviews the content presented in the symposium and provides a summary of major topics and key questions discussed in the workshop.

ABSTRACT: The present study investigated the effects of replacing part of the basal diet with 2-stage fermented feed (FF) (soybean hulls:rapeseed cake (2:1, m/m)) on the growth performance, immunity, antioxidant capacity, and intestinal health of Chahua chicken. A total of 160 Chahua chickens were randomly divided into 4 groups to receive a control diet or diet with 5%, 10%, or 15% of the basal diet replaced by FF, respectively for 56 d. The results showed that FF significantly improved the average daily gain (ADG) and average daily feed intake (ADFI) of Chahua chickens (P < 0.05). Furthermore, the serum immunoglobulin (Ig) A, glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) in Chahua chicken receiving the diet added with 15% FF significantly increased (P < 0.05). Chahua chicken in both the 10% and 15% groups showed increased serum IgG and IgM and decreased malondialdehyde. Serum interleukin-2 and interferon-gamma significantly increased in all FF groups. Compared with the CON group, higher ileal villus height (VH) was found in the 10% FF group. Treatment with FF significantly increased the ileal villus height/crypt depth (VH/CD) ratio, jejunal VH, and jejunal VH/CD ratio while reducing ileal and jejunal CD. The modified gut microbiota composition was observed in the Chahua chicken fed a diet containing FF, in particular, with the increased abundance of Faecalibacterium and Lactobacillus. The abundance of Lactobacillus significantly increased in the 10% and 15% FF groups (all P < 0.05). Correlation analysis revealed a positive correlation between Lactobacillus and VH (R = 0.38, P = 0.10, Figure 3B), AH/CD ratio (R = 0.63, P = 0.003), and a negative correlation with CD (R = −0.72, P = 0.001). These results indicate that FF improves immunity, antioxidant capacity, and intestinal health and consequently enhances growth performance in Chahua chicken.

Objective: Laryngeal cancer, characterized by high recurrence rates and a lack of effective biomarkers, has been associated with cuproptosis, a regulated cell death process linked to cancer progression. In this study, we aimed to explore the roles of cuproptosis-related genes in laryngeal cancer and their potential as prognostic markers and therapeutic targets. Methods: We collected comprehensive data from The Cancer Genome Atlas and Gene Expression Omnibus databases, including gene expression profiles and clinical data of laryngeal cancer patients. Using clustering and gene analysis, we identified cuproptosis-related genes with prognostic significance. A risk model was constructed based on these genes, categorizing patients into high- and low-risk groups for outcome comparison. Univariate and multivariate analyses were conducted to identify independent prognostic factors, which were then incorporated into a nomogram. Gene Set Enrichment Analysis was employed to explore pathways distinguishing high- and low-risk groups. Results: Our risk model, based on four genes, including transmembrane 2, dishevelled binding antagonist of β-catenin 1, stathmin 2, and G protein-coupled receptor 173, revealed significant differences in patient outcomes between high- and low-risk groups. Independent prognostic factors were identified and integrated into a nomogram, providing a valuable tool for prognostic prediction. Gene Set Enrichment Analysis uncovered up-regulated pathways specifically associated with high-risk patient samples. Conclusion: This study highlights the potential of cuproptosis-related genes as valuable prognostic markers and promising therapeutic targets in the context of laryngeal cancer. This research sheds light on new avenues for understanding and managing this challenging disease. Level of evidence: Level 4.

Epigenetic regulation contributes to the dysregulation of gene expression involved in cancer biology. Nevertheless, the roles of epigenetic regulators (ERs) in tumor immunity and immune response remain basically unclear. Here, we developed the epigenetic regulator in immunology (EPRIM) approach to identify immune-related ERs and comprehensively dissected the ER regulation in tumor immune response across 33 cancers. The identified immune-related ERs were related to immune infiltration and could stratify cancer patients into two risk groups in multiple independent datasets. These patient groups were characterized by distinct immune functions, immune infiltrates, driver gene mutations, and prognoses. Furthermore, we constructed an immune ER-based signature and highlighted its potential utility in predicting clinical benefit from immunotherapy and selecting therapeutic agents. Taken together, our identification and evaluation of immune-related ERs highlight the usefulness of EPRIM for the understanding of ERs in immune regulation and the clinical relevance in evaluation of cancer patient prognosis and response to immune checkpoint blockade therapy.

Based on single-cell sequencing of the hippocampi of 5× familiar Alzheimer's disease (5× FAD) and wild type mice at 2-, 12-, and 24-month of age, we found an increased percentage of microglia in aging and Alzheimer's disease (AD) mice. Blood brain barrier injury may also have contributed to this increase. Immune regulation by microglia plays a major role in the progression of aging and AD, according to the functions of 41 intersecting differentially expressed genes in microglia. Signaling crosstalk between C−C motif chemokine ligand (CCL) and major histocompatibility complex-1 bridges intercellular communication in the hippocampus during aging and AD. The amyloid precursor protein (APP) and colony stimulating factor (CSF) signals drive 5× FAD to deviate from aging track to AD occurrence among intercellular communication in hippocampus. Microglia are involved in the progression of aging and AD can be divided into 10 functional types. The strength of the interaction among microglial subtypes weakened with aging, and the CCL and CSF signaling pathways were the fundamental bridge of communication among microglial subtypes.

Background: Ewing's sarcoma is an extremely aggressive bone sarcoma in teenagers and adolescents. We managed to identify the potential role of ferroptosis-related genes (FRGs) in Ewing's sarcoma and its clinical prognostic value. Results: A total of 59 common differentially expressed FRGs were screened out. GO/KEGG enrichment and PPI network were executed. Based on 16 prognostic-related FRGs identified by univariate Cox regression in GSE17674, 2 molecular clusters were screened out via NMF consensus. Survival rate and immune infiltration were totally different in two clusters. Subsequently, multivariate/step Cox regression was conducted to identify 7 risk signatures (SLC2A1, PCK2, CHAC1, ATG13, PRKAA2, ARNT, and SIRT1). K-M survival (p = 1.785e-06) and ROC curves (with AUC value 0.816, 0877, 0.919 in 1, 3, 5 years) were plotted to assess the good predictive ability of risk model. ICGC dataset with K-M survival (p = 1.558e-02) and AUC value (0.886, 0.750, 0.709 in 1, 3, 5 years) was used to validate the risk model. Risk score and clinical features (gender, age stage status) were incorporated into a nomogram model. Immune microenvironment (IME) ingredients (ESTIMATE score, immune cells, immune-related pathways, and checkpoint genes) between two risk groups were also explored. High-risk group possessed an activated immune status compared to low-risk group. Finally, prognostic signatures exhibited perfect diagnostic ability in ES occurrence, and several drugs showed IC50 sensitivity to different risk groups. Conclusions: Our study identified 7 prognostic signatures of FRGs and explored related immune infiltration which provided new aspects for future research in Ewing's sarcoma.How to cite: Jiao X, Li Q, Xu X. Prognostic implication of a ferroptosis related gene signature associates with immunity in Ewing’s sarcoma. Electron J Biotechnol 2023;64. https://doi.org/10.1016/j.ejbt.2023.01.004.

The present study was performed to assess the effect of a commercial product Phyto AquaNity™ (Artepillin C and curcuminoids) supplementation on growth performance, immune parameters, and disease resistance of whiteleg shrimps (Litopenaeus vannamei) against White Spot Syndrome Virus (WSSV) infection. Shrimps of initial weight of 0.9–1 g were fed Phyto AquaNity™ at three dosages (0.0, 0.5 and 1.0 g kg−1) over 42 days. After the feeding period, growth performance parameters were significantly improved in the group of 1.0 g kg−1. The highest specific growth rate and feed efficiency were observed in the group 1.0 g kg−1 (P 0.05). Analysis of lysozyme gene expression was improved in groups fed with Phyto AquaNity™ and the lowest value was observed for the positive group (challenged & without Phyto AquaNity™ supplement). Overall, 1.0 g kg−1 of Phyto AquaNity™ showed better results in improving growth performance, immune responses, and survival in shrimps challenged with WSSV.

L-theanine, a non-protein amino acid in tea, has been widely studied as an immune enhancer in poultry, livestock, and rodents. However, no studies have been performed on the application of L-theanine in aquaculture feed. To fill this research gap, we investigated the effects of L-theanine as a feed additive on the growth performance, immune function, antioxidant capacity, and intestinal flora of female Chinese mitten crab (Eriocheir sinensis) using biochemical assays, real-time polymerase chain reaction, and 16 S rRNA gene sequencing. In total, 300 one-year-old female Chinese mitten crabs were randomly divided into treatment groups supplemented with 0 (control), 0.5%, 1.0%, 1.5%, and 2.0% L-theanine (L0–L4, respectively; n = 4 replicates per group with 15 crabs per replicate). After eight weeks, the total edible yield was significantly higher in all treatment groups than in the L0 group (P

Objective: Dysregulation of the immune system plays a vital role in the pathological process of vascular dementia, and this study aims to spot critical biomarkers and immune infiltrations in vascular dementia employing a bioinformatics approach. Methods: We acquired gene expression profiles from the Gene Expression Database. The gene expression data were analyzed using the bioinformatics method to identify candidate immune-related central genes for the diagnosis of vascular dementia. and the diagnostic value of nomograms and Receiver Operating Characteristic (ROC) curves were evaluated. We also examined the role of the VaD hub genes. Using the database and potential therapeutic drugs, we predicted the miRNA and lncRNA controlling the Hub genes. Immune cell infiltration was initiated to examine immune cell dysregulation in vascular dementia. Results: 1321 immune genes were included in the combined immune dataset, and 2816 DEGs were examined in GSE122063. Twenty potential genes were found using differential gene analysis and co-expression network analysis. PPI network design and functional enrichment analysis were also done using the immune system as the main subject. To create the nomogram for evaluating the diagnostic value, four potential core genes were chosen by machine learning. All four putative center genes and nomograms have a solid diagnostic value (AUC ranged from 0.81 to 0.92). Their high confidence level became unquestionable by validating each of the four biomarkers using a different dataset. According to GeneMANIA and GSEA enrichment investigations, the pathophysiology of VaD is strongly related to inflammatory responses, drug reactions, and central nervous system degeneration. The data and Hub genes were used to construct a ceRNA network that includes three miRNAs, 90 lncRNA, and potential VaD therapeutics. Immune cells with varying dysregulation were also found. Conclusion: Using bioinformatic techniques, our research identified four immune-related candidate core genes (HMOX1, EBI3, CYBB, and CCR5). Our study confirms the role of these Hub genes in the onset and progression of VaD at the level of immune infiltration. It predicts potential RNA regulatory pathways control VaD progression, which may provide ideas for treating clinical disease.

Listeria monocytogenes (Lm), a foodborne bacterium, can infect people and has a high fatality rate in immunocompromised individuals. Listeriolysin O (LLO), the primary virulence factor of Lm, is critical in regulating the pathogenicity of Lm. This review concludes that LLO may either directly or indirectly activate a number of host cell viral pathophysiology processes, such as apoptosis, pyroptosis, autophagy, necrosis and necroptosis. We describe the invasion of host cells by Lm and the subsequent removal of Lm by CD8 T cells and CD4 T cells upon receipt of the LLO epitopes from major histocompatibility complex class I (MHC-I) and major histocompatibility complex class II (MHC-II). The development of several LLO-based vaccines that make use of the pore-forming capabilities of LLO and the immune response of the host cells is then described. Finally, we conclude by outlining the several natural substances that have been shown to alter the three-dimensional conformation of LLO by binding to particular amino acid residues of LLO, which reduces LLO pathogenicity and may be a possible pharmacological treatment for Lm.

Acute myeloid leukemia (AML) is a prevalent hematological malignancy that exhibits a wide array of molecular abnormalities. Although traditional treatment modalities such as chemotherapy and allogeneic stem cell transplantation (HSCT) have become standard therapeutic approaches, a considerable number of patients continue to face relapse and encounter a bleak prognosis. The emergence of immune escape, immunosuppression, minimal residual disease (MRD), and other contributing factors collectively contribute to this challenge. Recent research has increasingly highlighted the notable distinctions between AML tumor microenvironments and those of healthy individuals. In order to investigate the potential therapeutic mechanisms, this study examines the intricate transformations occurring between leukemic cells and their surrounding cells within the tumor microenvironment (TME) of AML. This review classifies immunotherapies into four distinct categories: cancer vaccines, immune checkpoint inhibitors (ICIs), antibody-based immunotherapies, and adoptive T-cell therapies. The results of numerous clinical trials strongly indicate that the identification of optimal combinations of novel agents, either in conjunction with each other or with chemotherapy, represents a crucial advancement in this field. In this review, we aim to explore the current and emerging immunotherapeutic methodologies applicable to AML patients, identify promising targets, and emphasize the crucial requirement to augment patient outcomes. The application of these strategies presents substantial therapeutic prospects within the realm of precision medicine for AML, encompassing the potential to ameliorate patient outcomes.

Whether receptor activity-modifying proteins (RAMPs) play a key role in human cancer prognosis and immunity remains unknown. We used data from the public databases, The Cancer Genome Atlas, Therapeutically Applicable Research to Generate Effective Treatments, and the Genotype-Tissue Expression project. We utilized bioinformatics methods, R software, and a variety of online databases to analyze RAMPs. In general, RAMPs were significantly and differentially expressed in multiple tumors, and RAMP expression was closely associated with prognosis, immune checkpoints, RNA-editing genes, tumor mutational burden, microsatellite instability, ploidy, and stemness indices. In addition, the expression of RAMPs is strongly correlated with tumor-infiltrating lymphocytes in human cancers. Moreover, the RAMP co-expression network is largely involved in many immune-related biological processes. Quantitative reverse transcription polymerase chain reaction and Western blot proved that RAMP3 was highly expressed in glioma, and RAMP3 promoted tumor proliferation and migration. RAMPs exhibit potential as prognostic and immune-related biomarkers in human cancers. Moreover, RAMPs can be potentially developed as therapeutic targets or used to enhance the efficacy of immunotherapy.

Ammonia is a common toxicant in aquatic systems and one of the key factors affecting aquaculture. However, data on mollusks’ toxic response and coping mechanisms to ammonia nitrogen, especially freshwater mollusks, are still lacking. In this study, we evaluated the tolerance of a freshwater mollusk Solenaia oleivora to ammonia and investigated its coping mechanisms by combining physiological, metabolic, and transcriptomic analyses in the gills. The acute toxicity test revealed that the LC50–96 h (temperature-20 ℃, pH-7.4) of ammonia in S. oleivora was 63.29 mg/L. The physiological and TUNEL results showed that although 10 mg/L ammonia exposure increased the activities of antioxidant, immune and ammonia detoxification-related enzymes, it still caused oxidative damage and cell apoptosis of gill tissues. A total of 97 differential metabolites (DMs) and 3431 differential expressed genes (DEGs) were identified after ammonia stress. Among them, most DMs and DEGs were involved in immune response, antioxidant, cell apoptosis, carbohydrate metabolism, amino acid metabolism, and lipid metabolism. The enhancement of glycolysis and lipid metabolisms may provide energy for immune response and ammonia detoxification. In addition, glutamine synthesis, alanine synthesis and urea cycle were involved in ammonia nitrogen detoxification in the gill tissue of S. oleivora. Our results indicate that ammonia leads to individual death in S. oleivora, as wells as oxidative damage, cell apoptosis, immune response, and metabolic changes of gill tissues. The findings will provide valuable information to assess the potential ecological risk of environmental ammonia to freshwater mollusks and theoretical guidance for the healthy aquaculture of S. oleivora.

Background: Clear cell renal cell carcinoma (ccRCC), the most common type of RCC, typically produces no symptoms initially. Patients with ccRCC are at increased risk of developing advanced metastatic disease due to the absence of dependable and effective prognostic biomarkers. Therefore, it is particularly urgent to find optimal stratification of patients with ccRCC to distinguish the clinical benefits of different malignant degrees. Angiogenesis has a profound impact on the malignant behavior of renal cancer cells, and anti-angiogenic drugs have been applied to metastatic renal cancer patients. Moreover, immune function dysregulation is also a significant factor in tumorigenesis. We aim to construct a predictive model that combines angiogenesis and immune-related genes (AIRGs) to aid clinicians in predicting ccRCC prognosis. Methods: We gathered transcriptome and clinicopathology data from two datasets, the E-MTAB-1980 dataset and the Cancer Genome Atlas (TCGA). We utilized consensus clustering to find new molecular subgroups. A predictive model for the prognosis of angiogenesis-immune-associated genes (AIRGs) was conducted by the lasso and multivariate Cox regression analysis. The signature's predictive ability was then tested in different datasets. Meticulous scrutiny and comprehensive assessment were undertaken, both internally and externally, to establish the prognostic model. Analyses of immunogenomics were carried out to examine the relationship between risk scores and clinical/immune features, including immune cell infiltration, genomic alterations, and response to targeted and immunotherapy therapy. Results: Our prognostic signature, comprising 4 AIRGs, stood as an independent prognostic factor for ccRCC, while risk scores emerged as a novel indicator for forecasting overall survival. Risk scores exhibited significant associations with various immunophenotypic factors, such as oncogenic pathways, antitumor response, different immune cell infiltration, antitumor immunity, and response to targeted and immunotherapy therapy. Conclusions: AIRGs-based prognostic prediction model could effectively predict immunotherapy responses and survival outcomes of ccRCC.

Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes mellitus. Periodontitis (PD) is a microbially-induced chronic inflammatory disease that is thought to have a bidirectional relationship with diabetes mellitus. DN and PD are recognized as models associated with accelerated aging. This study is divided into two parts, the first of which explores the bidirectional causal relationship through Mendelian randomization (MR). The second part aims to investigate the relationship between PD and DN in terms of potential crosstalk genes, aging-related genes, biological pathways, and processes using bioinformatic methods. MR analysis showed no evidence to support a causal relationship between DN and PD (P = 0.34) or PD and DN (P = 0.77). Using the GEO database, we screened 83 crosstalk genes overlapping in two diseases. Twelve paired genes identified by Pearson correlation and the four hub genes in the key cluster were jointly evaluated as key crosstalk-aging genes. Using support vector machine recursive feature elimination (SVM-RFE) and maximal clique centrality (MCC) algorithms, feature selection established five genes as the key crosstalk-aging genes. Based on five key genes, an ANN diagnostic model with reliable diagnosis of two diseases was developed. Gene enrichment analysis indicates that AGE-RAGE pathway signaling, the complement system, and multiple immune inflammatory pathways may be involved in common features of both diseases. Immune infiltration analysis reveals that most immune cells are differentially expressed in PD and DN, with dendritic cells and T cells assuming vital roles in both diseases. Overall, although there is no causal link, CSF1R, CXCL6, VCAM1, JUN and IL1B may be potential crosstalk-aging genes linking PD and DN. The common pathways and markers explored in this study could contribute to a deeper understanding of the common pathogenesis of both diseases in the context of aging and provide a theoretical basis for future research.

Background: The recent COVID vaccinations have successfully reduced death and severity but did not stop the transmission of viruses by the emerging SARS-CoV-2 strain. There is a need for better and long-lasting dynamic vaccines for numerous prevailing strains and the evolving SARS-CoV-2 virus, necessitating the development of broad-spectrum strains being used to stop infection by reducing the spread rate and re-infection. The spike (S) glycoprotein is one of the proteins expressed commonly in the early phases of SARS-CoV-2 infection. It has been identified as the most immunogenic protein of SARS-CoV-2. Methods: In this study, advanced bioinformatics techniques have been exploited to design the novel multi-epitope vaccine using conserved S protein portions from widespread strains of SARS-CoV-2 to predict B cell and T cell epitopes. These epitopes were selected based on toxicity, antigenicity score and immunogenicity. Epitope combinations were used to construct the maximum potent multi-epitope construct with potential immunogenic features. EAAAK, AAY, and GPGPG were used as linkers to construct epitopes. Results: The developed vaccine has shown positive results. After the chimeric vaccine construct was cloned into the PET28a (+) vector for expression screening in Escherichia coli, the potential expression of the construct was identified. Conclusion: The construct vaccine performed well in computer-based immune response simulation and covered a variety of allelic populations. These computational results are more helpful for further analysis of our contract vaccine, which can finally help control and prevent SARS-CoV-2 infections worldwide.