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Introduction: Capping actin protein, gelsolin-like (CAPG) is a potential therapeutic target in various cancers. However, the potential immunotherapeutic effects and prognostic value of CAPG in uterine corpus endometrial carcinoma (UCEC) remain unclear. Methods: The characterization, methylation effects, prognostic value, targeted miRNAs of CAPG, and the correlation of CAPG with immune cell infiltration and ferroptosis in UCEC were investigated using multiple public databases and online tools. Furtherly, we explored the potential physiological function of CAPG using EdU and Transwell migration assays, identified the cell localization and expression of CAPG and GPX4 by immunofluorescence, and detected the intracellular Fe2+ levels using a FerroOrange fluorescent probe in Ishikawa cells. Additionally, the OncoPredict package was used to analyze the potential chemotherapeutic drugs for UCEC. Results: CAPG showed generally high expression in tumor group. The overall survival rate of the high-risk group was significantly lower than that of the low-risk group. Enrichment analysis indicated that CAPG is involved in immune-related pathways and is closely associated with the tumor microenvironment. CAPG expression levels were affected by abnormal DNA methylation and/or targeted miRNAs, infiltration levels and marker genes of various immune cells, thereby impacting immune response, ferroptosis, and patient prognosis. Ferroptosis analysis indicated that ALOX5 and VLDLR were the top CAPG-related ferroptosis markers; glutathione metabolism levels in tumor group were generally high, and decitabine was a ferroptosis inducer. CAPG-siRNA suppressed the cell proliferation and invasion, and markedly elevated the expression levels of immune-related genes IL8, TNF, TLR4 and the intracellular Fe2+ levels. CAPG co-located with GPX4 in nucleus and co-regulated ferroptosis and metabolism in Ishikawa cells. Moreover, four chemotherapy drugs showed better sensitivity to UCEC patients in the low-risk cohort. Conclusions: CAPG may serve as a potential biomarker of UCEC owing to its role in modulating the immune response and ferroptosis, providing novel perspectives for combined immunotherapy of UCEC. In UCEC, abnormal DNA methylation and/or targeted miRNAs expression may alter the expression of CAPG, thereby impacting immune response, ferroptosis, and patient prognosis. CAPG may affect TME by regulating the immune-related genes (such as IL8, TNF, TLR4) in infiltrating immune cells. CAPG not only regulates the proliferation and invasion of Ishikawa cells but also co-locates with GPX4 in nucleus and co-regulates ferroptosis and metabolism by combining with ALOX5, VLDLR markers and inducer decitabine. The changes of ferroptosis and TME co-modulate antitumor immunity in UCEC patients, while CAPG-related chemotherapeutic agents (paclitaxel, epirubicin, docetaxel, and cyclophosphamide) for UCEC patients show better sensitivity in the low-risk expression cohort. [ABSTRACT FROM AUTHOR]

Simple Summary: A 9-week experiment aimed to investigate the effects of dietary cobalt levels on the growth performance, antioxidant capacity, and immunity of largemouth bass. According to the results of growth performance, whole-body composition, antioxidant parameters in the liver, gene expression of the Nrf2 signaling pathway, and NF-κB signaling pathway, it was found that there was an improvement in the growth performance and feed utilization of largemouth bass fed with optimal dietary cobalt levels. Furthermore, cobalt has an important function in improving the antioxidant status and immune response of largemouth bass. Quadratic regression analyses based on the SGR and FCR showed that the optimal requirement was 0.24 and 0.26 mg/kg of dietary cobalt, respectively. A 9-week experiment investigated the effects of dietary cobalt levels on the growth performance, antioxidant capacity, and immunity of largemouth bass. Six feed groups were designed and each group received different cobalt levels, including 0.129 mg/kg (control group), 0.192 mg/kg, 0.201 mg/kg, 0.233 mg/kg, 0.277 mg/kg, and 0.316 mg/kg. The results show that the control group (0.129 mg/kg diet) had the lowest final body weight (FBW), weight gain rate (WGR), and specific growth rate (SGR), and the highest feed conversion ratio (FCR), when compared to the cobalt supplementation groups. Dietary cobalt levels of 0.192 mg/kg increased the body protein content and decreased the body moisture content. Regarding antioxidant capacity, the highest catalase (CAT) activity was found in the 0.277 mg/kg dietary cobalt group, while the malondialdehyde (MDA) content was significantly diminished; the total antioxidant capacity (T-AOC) content and glutathione peroxidase (GSH-Px) activity exhibited the highest values in the 0.192 mg/kg and 0.233 mg/kg dietary cobalt groups, respectively. Regarding gene expression, compared with the control group, the mRNA expression of sod was upregulated in the 0.192 mg/kg, 0.233 mg/kg, and 0.277 mg/kg dietary cobalt groups, while the mRNA expression of gpx was diminished when dietary cobalt levels were below 0.233 mg/kg. In addition, the highest il-10 and tgf-β mRNA expression levels were observed in the 0.201 mg/kg and 0.233 mg/kg dietary cobalt groups, respectively. According to the quadratic regression analysis based on the SGR and FCR, the optimal requirement was 0.24 and 0.26 mg/kg of dietary cobalt, respectively. [ABSTRACT FROM AUTHOR]

Background: Neuroblastoma exhibits substantial heterogeneity, which is intricately linked to various genetic alterations. We aimed to explore immune status in the peripheral blood and prognosis of patients with neuroblastoma with different genetic characteristics. Methods: We enrolled 31 patients with neuroblastoma and collected samples to detect three genetic characteristics. Peripheral blood samples were tested for immune cells and cytokines by fluorescent microspheres conjugated with antibodies and flow cytometry. Event-free survival (EFS) was analyzed using the Kaplan‒Meier method. Results: Twenty-two patients had genetic aberrations, including MYCN amplification in 6 patients, chromosome 1p deletion in 9 patients, and chromosome 11q deletion in 14 patients. Two genetic alterations were present in seven patients. The EFS was worse in patients with MYCN amplification or 1p deletion than in the corresponding group, whereas 11q deletion was a prognostic factor only in patients with unamplified MYCN. Changes in immune status revealed a decrease in the proportion of T cells in blood, and an increase in regulatory T cells and immunosuppression-related cytokines such as interleukin (IL)-10. The EFS of the IL-10 high-level group was lower than that of the low-level group. Patients with concomitant genetic alterations and a high level of IL-10 had worse EFS than other patients. Conclusions: Patients with neuroblastoma characterized by these genetic characteristics often have suppressed T cell response and an overabundance of immunosuppressive cells and cytokines in the peripheral blood. This imbalance is significantly associated with poor EFS. Moreover, if these patients show an elevated levels of immunosuppressive cytokines such as IL-10, the prognosis will be worse. [ABSTRACT FROM AUTHOR]

In the North, humans are exposed to a number of unfavourable natural and climatic factors, which can negatively affect the body’s functions. In the process of adaptation, homeostasis is maintained by imposing a strain on the relevant organs and systems, including the immune system, whose disruption is usually accompanied by changes in the cellular composition of the pool of peripheral blood leukocytes and is reflected in leukogram parameters. The purpose of this study was to establish the informative value of integral haematological indices for preventive detection of changes in the immune status. Materials and methods. We examined 75 volunteers, including 52 residents of Konosha settlement and 23 residents of the city of Arkhangelsk (mean age 42 ± 10 and 44 ± 14 years, respectively). The subjects’ complete blood count was performed using the Medonic M20 cell analyser (Boule Medical AB, Sweden), and their leukocyte formula was calculated. The leukocyte intoxication index, nuclear index, allergization index and leukocyte shift index were calculated. Results. It was established that apparently healthy people living in the same region but in areas differing in natural and climatic conditions have statistically significant differences in the cellular composition of the leukocyte pool. In residents of the northern part of the Arkhangelsk Region (the city of Arkhangelsk), lymphocyte and band neutrophil count, as well as mean nuclear index and mean allergization index exceed the upper limits of their reference intervals. At the same time, residents of the region’s southern part (Konosha settlement) had a higher frequency of exceeding the upper limit of the reference interval of the leukocyte intoxication index. Integral haematological indices allow us to identify changes in the immune status at the preventive stage; their calculation can serve as an effective way to assess the degree of allergization, the level of endogenous intoxication and the reactivity of the immune system. Due to the simplicity and accessibility of the analysis, one can quickly obtain results and use them both for population screening and in surveillance studies.

Abstract Objective Gastric cancer (GC) is characterized by its high malignancy and poor prognosis. However, the role of Inhibin subunit beta A (INHBA) in GC remains insufficiently understood. This study aims to comprehensively evaluate the clinical significance, biological roles, and possible mechanisms of INHBA in GC. Methods Expression levels and survival analyses of the Inhibin beta family were assessed using online databases. A prediction model based on INHBA was developed. In addition, the associations between INHBA expression and immune status, and chemotherapy sensitivity were explored. In vitro experiments were conducted to investigate the biological impact of INHBA on GC cells. Pyrosequencing and the DNA methylation inhibitor, 5-AZA-2’-deoxycytidine (5-AZA-dC) were employed to elucidate the mechanisms underlying INHBA function. Results Our findings revealed that INHBA exhibited high expression in GC patients, and elevated INHBA expression correlated with worse outcomes. We developed a novel nomogram incorporating INHBA, age, and tumor node metastasis (TNM) stage to predict the prognosis of GC patients. Additionally, INHBA was found to be associated with suppressed infiltration of immune cells and chemosensitivity. Functionally, INHBA promoted the proliferation and invasiveness of GC cells. Mechanistically, pyrosequencing revealed DNA Hypomethylation of INHBA in the first exon region, and the effects of INHBA silencing were rescued by 5-AZA-dC treatment. Conclusion Our study suggests that DNA hypomethylation of INHBA contributes to the progression of GC. Furthermore, INHBA holds promise as a valuable biomarker for prognostic evaluation and immune status prediction in GC patients.

Abstract Background Neuroblastoma exhibits substantial heterogeneity, which is intricately linked to various genetic alterations. We aimed to explore immune status in the peripheral blood and prognosis of patients with neuroblastoma with different genetic characteristics. Methods We enrolled 31 patients with neuroblastoma and collected samples to detect three genetic characteristics. Peripheral blood samples were tested for immune cells and cytokines by fluorescent microspheres conjugated with antibodies and flow cytometry. Event-free survival (EFS) was analyzed using the Kaplan‒Meier method. Results Twenty-two patients had genetic aberrations, including MYCN amplification in 6 patients, chromosome 1p deletion in 9 patients, and chromosome 11q deletion in 14 patients. Two genetic alterations were present in seven patients. The EFS was worse in patients with MYCN amplification or 1p deletion than in the corresponding group, whereas 11q deletion was a prognostic factor only in patients with unamplified MYCN. Changes in immune status revealed a decrease in the proportion of T cells in blood, and an increase in regulatory T cells and immunosuppression-related cytokines such as interleukin (IL)-10. The EFS of the IL-10 high-level group was lower than that of the low-level group. Patients with concomitant genetic alterations and a high level of IL-10 had worse EFS than other patients. Conclusions Patients with neuroblastoma characterized by these genetic characteristics often have suppressed T cell response and an overabundance of immunosuppressive cells and cytokines in the peripheral blood. This imbalance is significantly associated with poor EFS. Moreover, if these patients show an elevated levels of immunosuppressive cytokines such as IL-10, the prognosis will be worse.

Adaptive restructuring gets disrupted due to a reduction in the body’s reserve capacity at increased stress on the functional systems in response to the combined effects of adverse factors, including climatic. Determination of the state of blood transport systems and immune homeostasis broadens our understanding of how human body systems operate under adverse conditions of the North. The purpose of this article was to assess the state of the transport components of the blood system in relation to the immune status of the population of the European North of Russia. Materials and methods. A survey of 789 residents of the Arkhangelsk Region aged 21 to 55 years was conducted and their blood system parameters were analysed taking into account the levels of haptoglobin, transferrin, immunoglobulins and lipid transport complexes with their structural ligands. Results. Residents of the European North of Russia showed increased levels of transferrin in 31.8 %, IgM in 7.6 %, IgE in 7.8 % and low-density lipoproteins in 10.2 % of cases, as well as a deficit in IgA in 55.6 % and high-density lipoprotein apoA-I ligand in 56.2 % of cases. Elevated blood transferrin concentrations are associated with low CD71+ lymphocyte count, which reflects the inhibition of activation and proliferation processes when the signal from the CD3+ receptor is blocked. A decrease in the level of transferrin CD71+ receptors on lymphocytes is manifested in disturbed immunoglobulin class switching with the formation of IgA deficit, which is compensated by IgM and IgE. Increased immunoglobulin content ensures effective binding of metabolic products with autoantigen properties (low-density lipoproteins) when the functional properties of high-density lipoproteins are impaired due to the structural apoA-I deficit. Determination of the transport components of the blood system in relation to the state of the immune system is informative for assessing the risk of disruption of adaptive mechanisms.

Abstract Background Diet regulates rumen microbiota, which in turn affects animal health. The present study evaluated the response of rumen microbiota and the immune system of lambs to a fermented total mixed ration diet. Methods A total of 30 lambs were assigned into two groups: a group fed an unfermented high‐fiber diet (total mixed ration [TMR]) and a group fed an fermented low‐fiber diet (fermented TMR [FTMR]). Results The results showed that FTMR markedly (p

Background: The increase in the intensity of agricultural production is associated with the action of various stress factors on the organism of birds, which can lead to negative consequences. Prevention of the development of stress conditions in farm birds, particularly broiler chickens, in industrial production is the most important task facing scientists and practitioners. Aim: The objective of this study was to investigate the effect of a combined probiotic preparation and zinc glycinate on the indicators of the immunity, biochemical parameters and antioxidant status. Methods: The study was conducted on broilers of Arbor Acres cross: the birds in the negative control group received a balanced feed mixture, a mineral and vitamin premix without zinc; the positive control group treated with an injection of cyclophosphamide and received the balanced feed with the mineral and vitamin premix without zinc; in experimental group I, broilers was treated with the injection of cyclophosphamide and received balanced feed, probiotic and zinc glycinate; in experimental group II, broilers received balanced feed, probiotic and zinc glycinate. At the end of the experiment, some blood from the wing vein was collected for evaluation of hematological and biochemical blood parameters using automatic morphological and biochemical analyzers, evaluation of immune status by enzyme immunoassay and antioxidant status by colorimetric method. Results: It was found that the developed strategy nutrition leveled the effects of immunosuppression - there was an increase in the level of lymphocytes, interleukin-4 and interleukin-10; level of cholesterol, triglycerides, glucose and total protein tended to the control values; there was a significant increase in serum interleukin-2 and interferon gamma; increase in total protein on the background of triglycerides decrease in broilers of experimental group II. An increase in the activity of superoxide dismutase and catalase against the background of a decrease in the level of malonic dialdehyde was revealed in the experimental groups. Conclusion: The developed strategy of broiler chicken nutrition can be used for successful protection of birds from immunodeficiency states, improvement of antioxidant status and maintenance of complete protein and lipid metabolism. [Open Vet J 2024; 14(9.000): 2181-2191]

Abstract PANoptosis is engaged in the program of immune response and carcinogenicity. Nonetheless, the actual impacts of PANoptosis on clinical management and oncology immunity in hepatocellular carcinoma (HCC) are not fully grasped. RNA-seq-derived computations were conducted to sort out the molecular subtypes and elucidate the disparities based on PANoptosis molecules. Single-cell sequencing (scRNA-seq) tools including Cytotrace and Addmodulescore were extracted to characterize diversification potency and quantify the PANoptosis motion. Transcriptional factors were inferred by the pySCENIC package and Cellchat program scrutinized the intercellular exchange across cell compartments. The PANoptosis score system originated by incorporating 10 machine learning algorithms and 101 compositions to project clinical results and deteriorate tendencies. Circulatory PANoptosis-associated protein HSP90AA1 was determined by enzyme-linked immunosorbent assay (ELISA). HCC individuals could be categorized into low- and high-PANoptosis groups with diverse biogenic and pharmacotherapy heterogeneity. Individuals in the elevated PANoptosis subtype were characterized as “hot tumor” conveying the increased presence of immunogenicity while reiterating an explicit negative connection with tumor stemness. Compared to immune and stromal cells, cancerous cells showcased decreased PANoptosis and heightened PANoptosis malignant cell subgroups might be tied to a substantial level of genomic expression of SREBF2, JUND, GATAD1, ZBTB20, SMAD5 and implied a more aggressive potential. The PANoptosis index, derived from machine learning, has been established to provide succinct frameworks for predicting outcomes and clarified the noteworthy utility of conventional regimens, as the differentiated power of HCC occurred together with vascular invasion and hepatocellular adenoma (HCA). The experiment confirmed that the circulating HSP90AA1 was aberrantly augmented in HCC patients, thus demonstrating its potential as a discriminatory biomarker. We systematically deciphered the molecular and immune ecosystem traits of PANoptosis in bulk and scRNA-seq degrees, which may deliver advantageous insights for customized treatment, awareness of the pathological process and prognosis scrutiny for HCC patients.

Introduction. Campylobacteriosis is among the leading causes of acute gastrointestinal infections. The severity of campylobacteriosis and the development of long-term complications may be influenced by the genotype of the pathogen, whose biological properties can affect immune response parameters. The aim of the study was to identify common genotypes of epidemic clones of Campylobacter pathogens and to investigate characteristics of the immune response and severity of the disease. Materials and methods. The study included 203 patients aged from 1 month to 17 years with campylobacteriosis who underwent treatment at the clinic of the Federal State Budgetary Institution "DNKCIB FMBA" in 2019–2021. The diagnosis was confirmed using polymerase chain reaction method. Patient samples were also analyzed using culture-based methods. Total DNA was extracted using the QIAamp DNA Mini Kit. Genetic determinants encoding virulence factors and MLST typing were performed using the ResFinder program. The immune status of patients was assessed on days 1 and 7 of the illness. Immunological investigation included measurement of serum immunoglobulin concentrations (IgA, IgM, IgG), C-reactive protein, and cytokines (IL-1β, IL-1, IL-2, IL-4, IL-5, IL-6, IL- 7, IL-8, IL-10, TNF-α, and IFN-γ). Results. When analyzing the frequency of detection of Campylobacter sequence types in children with clinical intestinal infections, it was found that the profile of isolated isolates is most similar to those from countries of North America (USA and Canada), Northern Europe (Great Britain, Holland ) and Scandinavia (Denmark, Sweden, Finland). Identification of a pathogen with the flgE+, cdtA+, cdtC+ genotype was accompanied by a statistically significant increase in the level of IL-8 and a decrease in the content of IgA in the peripheral blood serum, which reflected the low efficiency of the immune response during infection with Campylobacter and predetermined the severe course of the infectious process during the disease.

Abstract Background Interventional valve implantation into the inferior vena cava (CAVI) lowers venous congestion in patients with tricuspid regurgitation (TR). We evaluated the impact of a reduction of abdominal venous congestion following CAVI on circulating immune cells and inflammatory mediators. Methods Patients with severe TR were randomized to optimal medical therapy (OMT) + CAVI (n = 8) or OMT (n = 10). In the OMT + CAVI group, an Edwards Sapien XT valve was implanted into the inferior vena cava. Immune cells and inflammatory mediators were measured in the peripheral blood at baseline and three-month follow-up. Results Leukocytes, monocytes, basophils, eosinophils, neutrophils, lymphocytes, B, T and natural killer cells and inflammatory markers (C-reactive protein, interferon-gamma, interleukin-2, -4, -5, -10, and tumor necrosis factor-alpha) did not change substantially between baseline and three-month follow-up within the OMT + CAVI and OMT group. Conclusion The present data suggest that reduction of venous congestion following OMT + CAVI may not lead to substantial changes in systemic inflammation within a short-term follow-up. Clinical trial registration NCT02387697 Graphical Abstract

PANoptosis is engaged in the program of immune response and carcinogenicity. Nonetheless, the actual impacts of PANoptosis on clinical management and oncology immunity in hepatocellular carcinoma (HCC) are not fully grasped. RNA-seq-derived computations were conducted to sort out the molecular subtypes and elucidate the disparities based on PANoptosis molecules. Single-cell sequencing (scRNA-seq) tools including Cytotrace and Addmodulescore were extracted to characterize diversification potency and quantify the PANoptosis motion. Transcriptional factors were inferred by the pySCENIC package and Cellchat program scrutinized the intercellular exchange across cell compartments. The PANoptosis score system originated by incorporating 10 machine learning algorithms and 101 compositions to project clinical results and deteriorate tendencies. Circulatory PANoptosis-associated protein HSP90AA1 was determined by enzyme-linked immunosorbent assay (ELISA). HCC individuals could be categorized into low- and high-PANoptosis groups with diverse biogenic and pharmacotherapy heterogeneity. Individuals in the elevated PANoptosis subtype were characterized as "hot tumor" conveying the increased presence of immunogenicity while reiterating an explicit negative connection with tumor stemness. Compared to immune and stromal cells, cancerous cells showcased decreased PANoptosis and heightened PANoptosis malignant cell subgroups might be tied to a substantial level of genomic expression of SREBF2, JUND, GATAD1, ZBTB20, SMAD5 and implied a more aggressive potential. The PANoptosis index, derived from machine learning, has been established to provide succinct frameworks for predicting outcomes and clarified the noteworthy utility of conventional regimens, as the differentiated power of HCC occurred together with vascular invasion and hepatocellular adenoma (HCA). The experiment confirmed that the circulating HSP90AA1 was aberrantly augmented in HCC patients, thus demonstrating its potential as a discriminatory biomarker. We systematically deciphered the molecular and immune ecosystem traits of PANoptosis in bulk and scRNA-seq degrees, which may deliver advantageous insights for customized treatment, awareness of the pathological process and prognosis scrutiny for HCC patients. [ABSTRACT FROM AUTHOR]

Background: The increase in the intensity of agricultural production is associated with the action of various stress factors on the organism of birds, which can lead to negative consequences. Prevention of the development of stress conditions in farm birds, particularly broiler chickens, in industrial production, is the most important task facing scientists and practitioners. Aim: The objective of this study was to investigate the effect of a combined probiotic preparation and zinc glycinate on the indicators of immunity, biochemical parameters, and antioxidant status. Methods: The study was conducted on broilers of Arbor Acres cross: the birds in the negative control group received a balanced feed mixture, a mineral and vitamin premix without zinc; the positive control group treated with an injection of cyclophosphamide and received the balanced feed with the mineral and vitamin premix without zinc; in experimental group I, broilers was treated with the injection of cyclophosphamide and received balanced feed, probiotic and zinc glycinate; in experimental group II, broilers received balanced feed, probiotic and zinc glycinate. At the end of the experiment, some blood from the wing vein was collected for evaluation of hematological and biochemical blood parameters using automatic morphological and biochemical analyzers, evaluation of immune status by enzyme immunoassay, and antioxidant status by colorimetric method. Results: It was found that the developed strategy nutrition leveled the effects of immunosuppression - there was an increase in the level of lymphocytes, interleukin-4, and interleukin-10; the level of cholesterol, triglycerides, glucose, and total protein (TP) tended to the control values; there was a significant increase in serum interleukin-2 and interferon gamma; increase in TP on the background of triglycerides decreased in broilers of experimental group II. An increase in the activity of superoxide dismutase and catalase against the background of a decrease in the level of malonic dialdehyde was revealed in the experimental groups. Conclusion: The developed strategy of broiler chicken nutrition can be used for the successful protection of birds from immunodeficiency states, improvement of antioxidant status, and maintenance of complete protein and lipid metabolism. [ABSTRACT FROM AUTHOR]

Background: Diet regulates rumen microbiota, which in turn affects animal health. The present study evaluated the response of rumen microbiota and the immune system of lambs to a fermented total mixed ration diet. Methods: A total of 30 lambs were assigned into two groups: a group fed an unfermented high‐fiber diet (total mixed ration [TMR]) and a group fed an fermented low‐fiber diet (fermented TMR [FTMR]). Results: The results showed that FTMR markedly (p < 0.05) increased average daily gain and dry matter intake compared to TMR. The FTMR diet increased the relative abundance of Veillonellaceae_UCG‐001 and decreased the diversity of undesirable microbiota despite stable overall microbial community diversity. Serum metabolomic analysis combined with enrichment analysis showed that serum metabolites were affected by the FTMR and metabolic pathways, and the FTMR diet significantly (p < 0.05) influenced amino acid metabolism of lambs. There was a decrease in inflammatory factors in the FTMR treatment, indicating that inflammatory factors followed the same trajectory as changes in microbial community structure and function. Conclusions: Overall, the FTMR diet reduced undesirable microbiota diversity, thereby regulating host amino acid metabolism and improving immune status. [ABSTRACT FROM AUTHOR]

Simple Summary: Simple Summary: The ban on the use of antibiotics as growth promoters has compelled the exploration of other alternatives. Acidifiers and essential oils are promising alternatives for antibiotics in poultry production, especially acidifiers provided in drinking water as they are more convenient and reduce the potential corrosion of processing equipment and loss during granulation. This study investigated the effect of acidifier and essential oil supplementation in drinking water on growth performance, intestinal digestive capacity, and immune status in broiler chickens. The results showed that a combination of acidifiers (with formic acid and propionic acid as active ingredients) and essential oils (with eucalyptus essential oil, mint essential oil, and cinnamaldehyde as active ingredients) improved the immune function of broilers and reduced the growth of potential pathogenic microorganisms in the waterline and excreta. In order to evaluate the effects of acidifiers and essential oils in drinking water on growth, intestinal digestive capacity, and immune status in broilers, a total of 480, 1-day-old Arbore Acres broilers were randomly assigned to four treatments including normal tap water (Ctr) and tap water supplemented with acidifier I (ACI), acidifier I and essential oils (ACI+EO), and acidifier II (ACII). Both ACI+EO and ACII increased final body weight. The pH value of the crop and gizzards was reduced by ACI+EO, and ACII decreased the pH values of the proventriculus and gizzards (p < 0.05). Compared with control group, ACI, ACI+EO, ACII significantly enhanced lipase activity in jejunum but ACII decreased the level of serum total cholesterol and total triglyceride (p < 0.05). Compared with the control group, ACI+EO and ACII significantly increased the relative weight of the spleen, increased the level of serum IgA and IgM, and decreased E. coli in excreta, while ACII significantly decreased Salmonella in excreta (p <0.05). All treatments significantly increased Lactobacillus in excreta. In conclusion, ACI+EO improved immune status and ACII was effective in reducing Salmonella and promoting Lactobacillus, contributing to intestinal health. [ABSTRACT FROM AUTHOR]

In 2018, classical swine fever (CSF) reemerged in Gifu Prefecture, Japan, after 26 years of absence, and vaccination of domestic pigs using a live attenuated vaccine was initiated in 2019. Because the vaccine efficacy in piglets is influenced by the maternal antibody levels, vaccination should be administered at the optimal age by assuming the antibody level in sows. In this study, the shift in the antibody titer distribution in sows due to the initiation of vaccination to naïve herds and its influence on the vaccine-induced immunity rate in fattening pigs were investigated for 3 years. The results indicated that higher antibody titers were induced in first-generation sows after vaccine initiation because they were immunologically naïve, but the distribution of antibody titers shifted to lower levels along with their replacement with second-generation sows. The average vaccination age of fattening pigs became earlier year by year, and the vaccine-induced antibody rate was almost ≥80%. Based on the estimation of the optimal age for vaccination, it was found that vaccination at a younger age may reduce the risk of CSF infection. Taken together, the risk of CSF outbreaks can be reduced by administering vaccines at the optimal age based on the sequential monitoring of the sow's immune status. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that postbiotics possess bioactivities comparable to those of probiotics. Therefore, our experiment aimed to evaluate the effects of postbiotics derived from Enterococcus faecium on the growth performance and intestinal health of growing male minks. A total of 120 growing male minks were randomly assigned to 4 groups, each with 15 replicates of 2 minks. The minks in the 4 groups were fed a basal diet supplemented with 0 (control), 0.05, 0.1, and 0.15% postbiotics derived from E. faecium (PEF), respectively. Compared to the control, PEF improved feed/gain (F/G) during the first 4 weeks and the entire 8 weeks of the study (p < 0.05); in addition, 0.1% PEF improved average daily gain (ADG) during the first 4 weeks and the entire 8 weeks of the study (p < 0.05), while 0.15% PEF improved ADG during the first 4 weeks of the study (p < 0.05). Consequently, 0.1% PEF minks displayed greater body weight (BW) at weeks 4 and 8 (p < 0.05), and 0.15% PEF minks had greater BW at week 4 (p < 0.05) than minks in the control. Furthermore, compared to the control, both 0.05 and 0.1% PEF enhanced the apparent digestibility of crude protein (CP) and ether extract (EE) (p < 0.05) in the initial 4 weeks, while both 0.1 and 0.15% PEF enhanced the apparent digestibility of CP and DM in the final 4 weeks (p < 0.05). Additionally, trypsin activity was elevated in the 0.1 and 0.15% PEF groups compared to the control (p < 0.05). In terms of intestinal morphology, PEF increased the villus height and villus/crypt (V/C) in the jejunum (p < 0.05), and both 0.1 and 0.15% PEF decreased the crypt depth and increased the villus height and V/C in the duodenum (p < 0.05) compared to the control group. Supplementation with 0.1% PEF increased the SIgA levels but decreased the IL-2, IL-8, and TNF-a levels in the jejunum (p < 0.05). Compared to the control, E. faecium postbiotics decreased the relative abundances of Serratia and Fusobacterium (p < 0.05). In conclusion, the results indicate that the growth performance, digestibility, immunity, and intestine development of minks are considerably affected by E. faecium postbiotics. In particular, dietary supplementation with 0.1% E. faecium postbiotics provides greater benefits than supplementation with 0.05 and 0.15%. [ABSTRACT FROM AUTHOR]

Background: Interventional valve implantation into the inferior vena cava (CAVI) lowers venous congestion in patients with tricuspid regurgitation (TR). We evaluated the impact of a reduction of abdominal venous congestion following CAVI on circulating immune cells and inflammatory mediators. Methods: Patients with severe TR were randomized to optimal medical therapy (OMT) + CAVI (n = 8) or OMT (n = 10). In the OMT + CAVI group, an Edwards Sapien XT valve was implanted into the inferior vena cava. Immune cells and inflammatory mediators were measured in the peripheral blood at baseline and three-month follow-up. Results: Leukocytes, monocytes, basophils, eosinophils, neutrophils, lymphocytes, B, T and natural killer cells and inflammatory markers (C-reactive protein, interferon-gamma, interleukin-2, -4, -5, -10, and tumor necrosis factor-alpha) did not change substantially between baseline and three-month follow-up within the OMT + CAVI and OMT group. Conclusion: The present data suggest that reduction of venous congestion following OMT + CAVI may not lead to substantial changes in systemic inflammation within a short-term follow-up. Clinical trial registration: NCT02387697 [ABSTRACT FROM AUTHOR]

Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1 (C1GALT1) is known to play a critical role in the development of gastric cancer, but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer risk. By using the genome-wide association study data from the database of Genotype and Phenotype (dbGAP), we evaluated such associations with a multivariable logistic regression model and identified that the rs35999583G>C in C1GALT1 was associated with gastric cancer risk (odds ratio, 0.83; 95% confidence interval [CI], 0.75–0.92; P = 3.95 × 10−4). C1GALT1 mRNA expression levels were significantly higher in gastric tumor tissues than in normal tissues, and gastric cancer patients with higher C1GALT1 mRNA levels had worse overall survival rates (hazard ratio, 1.33; 95% CI, 1.05–1.68; Plog-rank = 1.90 × 10−2). Furthermore, we found that C1GALT1 copy number differed in various immune cells and that C1GALT1 mRNA expression levels were positively correlated with the infiltrating levels of CD4+ T cells and macrophages. These results suggest that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 as a promising predictor of gastric cancer susceptibility and immune status. [ABSTRACT FROM AUTHOR]

The whiteleg shrimp, Penaeus vannamei, is a highly valued and globally produced crustacean species. However, the rising cost of shrimp feed, exacerbated by increasing cereal prices, prompts the exploration of cost-effective and sustainable formulations. This study investigates the potential of Salicornia ramosissima biomass by-product (the non-edible part) as a substitute for wheat meal in juvenile shrimp diets, aiming to create sustainable formulations. Particularly to assess the impact of incorporating S. ramosissima into shrimp aquafeeds on various aspects of shrimp development, including growth performance, survival, immune status, and oxidative status. A commercial-like diet was formulated and served as control, whereas four other diets contained S. ramosissima stems or a combination of leaves and seeds, both at inclusion levels of 5% and 10%. Shrimps were fed the experimental diets for 31 and 55 days, followed by a bacterial bath challenge test to gauge their immune response to pathogens. At the end of the feeding period, growth performance and survival rates remained consistent across all diets. However, shrimp fed diets with S. ramosissima consumed more feed to achieve similar weights of those fed the control diet, particularly in diets containing leaves and seeds at a 10% inclusion level, likely due to lower digestibility of dry matter, lipids, and energy. While S. ramosissima biomass inclusion did not affect shrimp weight, relative growth rate, or survival, it did lead to higher feed conversion ratios and feed intake. Additionally, S. ramosissima inclusion affected shrimps’ overall body composition, particularly moisture and ash content. S. ramosissima inclusion modulated antioxidant enzyme activity in the shrimp’s hepatopancreas, indicating potential health improvements. The observed gene expression changes related to antioxidant enzymes, points to an overall down-regulation with the inclusion of S. ramosissima. Despite challenges in feeding efficiency, the inclusion of S. ramosissima, especially stems, shows promise in reducing feed costs by utilizing a food agro-industrial by-products (non edible parts). Furthermore, S. ramosissima inclusion led to subtle changes in certain plasma humoral parameters. In conclusion, this study highlights the potential of this halophyte as a functional feed ingredient capable of enhancing shrimp’s antioxidant response, aligning with global resource optimization and sustainability initiatives.

IntroductionCapping actin protein, gelsolin-like (CAPG) is a potential therapeutic target in various cancers. However, the potential immunotherapeutic effects and prognostic value of CAPG in uterine corpus endometrial carcinoma (UCEC) remain unclear.MethodsThe characterization, methylation effects, prognostic value, targeted miRNAs of CAPG, and the correlation of CAPG with immune cell infiltration and ferroptosis in UCEC were investigated using multiple public databases and online tools. Furtherly, we explored the potential physiological function of CAPG using EdU and Transwell migration assays, identified the cell localization and expression of CAPG and GPX4 by immunofluorescence, and detected the intracellular Fe2+ levels using a FerroOrange fluorescent probe in Ishikawa cells. Additionally, the OncoPredict package was used to analyze the potential chemotherapeutic drugs for UCEC.ResultsCAPG showed generally high expression in tumor group. The overall survival rate of the high-risk group was significantly lower than that of the low-risk group. Enrichment analysis indicated that CAPG is involved in immune-related pathways and is closely associated with the tumor microenvironment. CAPG expression levels were affected by abnormal DNA methylation and/or targeted miRNAs, infiltration levels and marker genes of various immune cells, thereby impacting immune response, ferroptosis, and patient prognosis. Ferroptosis analysis indicated that ALOX5 and VLDLR were the top CAPG-related ferroptosis markers; glutathione metabolism levels in tumor group were generally high, and decitabine was a ferroptosis inducer. CAPG-siRNA suppressed the cell proliferation and invasion, and markedly elevated the expression levels of immune-related genes IL8, TNF, TLR4 and the intracellular Fe2+ levels. CAPG co-located with GPX4 in nucleus and co-regulated ferroptosis and metabolism in Ishikawa cells. Moreover, four chemotherapy drugs showed better sensitivity to UCEC patients in the low-risk cohort.ConclusionsCAPG may serve as a potential biomarker of UCEC owing to its role in modulating the immune response and ferroptosis, providing novel perspectives for combined immunotherapy of UCEC.

Background. The profession of firefighters is characterized by the impact of a number of dangerous factors, including toxic fire products, which is currently not taken into account by the medical service and medical and psychological support units. To increase the effectiveness of measures aimed at preventing non-communicable diseases, protecting the health and improving the professional longevity of firefighters, it is necessary to take into account the influence of harmful professional factors that influence the formation of various pathologies. Intention of the study: to determine laboratory parameters characterizing the toxic etiology of the formation of fatty liver degeneration in firefighters. Methodology. To determine the features of the pathogenesis of non-alcoholic fatty liver disease, 246 male patients suffering and not suffering from fatty liver degeneration were examined. The tasks were solved by analyzing the results obtained using toxicological, biochemical, and immunological techniques. Results and Discussion. Laboratory markers of fatty liver degeneration have been determined. The peculiarities of the regulation of the immune system in employees of the GPS FPS of the Ministry of Emergency Situations of Russia suffering from fatty liver degeneration have been revealed. Conclusions. Multidirectional changes in instrumental, biochemical and immunological parameters were revealed in firefighters suffering from fatty liver degeneration compared to the control group with the same pathology, indicating the peculiarities of homeostasis disorders, which determines the difference in pathogenesis caused by chronic toxic damage by fire products.

The prospective effect of beetroot extract (Beta vulgaris L.) to resist the toxic effect of lead (Pb) and enhance the immune status and antioxidant enzyme of the Nile tilapia (Oreochromis niloticus) was studied. Fish specimens were divided into 4 groups: C (control group), Pb (group subjected to lead), T1, and T2 (groups injected intraperitoneal with 100 and 150mg/ kg of beetroot extract 2 weeks before being subjected to Pb, respectively). The effects were addressed on the humoral immune parameters, (antiproteases, lysozyme total protein, and globulin) and antioxidant enzymes [Glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and peroxidase (POX) activities], as well as some biochemical parameters. Pb accumulation was studied in gills, liver, and muscle tissues. The results revealed a significant enhancement in some immune parameters viz. a lysozyme and total protein in T1 groups compared to other groups, especially with the Pb group which showed the lowest significant values (P< 0.05). The groups injected with beetroot extract showed the lowest significant values (P< 0.05) of Pb accumulation in tissues compared to Pb group. While, T1 group recorded a significant increase (P< 0.05) in hepatic protein content, GST, SOD, CAT, and POX, respectively, compared to the Pb group. Moreover, Pb group showed a significant decrease compared to the control group. Most of the biochemical parameters, including glucose, cholesterol, AST, and uric acid recorded the highest values in Pb group compared to the other groups, but without significant difference. The albumin value of T1 group showed the highest significant values compared to other groups. To conclude, the injection of the Nile tilapia with 100mg/ kg of beetroot extract may contribute to protecting fish from the harmful effects of lead by enhancing the immune system and antioxidant enzymes, and improving the general fish health. [ABSTRACT FROM AUTHOR]

Simple Summary: SCFAs are considered functional ingredients as they promote the growth and health of fish. This work aimed to assess the effect of short-chain fatty acids (SCFAs) on the immune status of the European sea bass gut through the ex vivo use of intestinal explants. The ex vivo technique significantly reduces the number of animals to be used, according to the guidelines of the 3Rs. The present results are important to understand how European sea bass respond to a bacterial infection after the administration of SCFAs and for the evaluation of functional ingredients used in aquaculture. This study aimed to evaluate the intestinal interactions between three short-chain fatty acids (SCFA), namely, acetate, propionate, and butyrate, and pathogenic bacteria (Vibrio anguillarum) in intestinal explants of European sea bass (Dicentrarchus labrax) juveniles. The anterior intestine of 12 fish with an average weight of 100 g (killed by excess anesthesia with 2-phenoxyethanol) were sampled and placed in 24-well plates. The experimental treatments consisted of a control medium and a control plus 1 mM or 10 mM of sodium acetate (SA), sodium butyrate (SB), and sodium propionate (SP). After 2 h of incubation, the explants were challenged with Vibrio anguillarum at 1 × 107 CFU/mL for 2 h. After the bacterial challenge, and regardless of the SCFA treatment, the oxidative stress-related genus catalase (cat) and superoxide dismutase (sod) were down-regulated and glutathione peroxidase (gpx) was up-regulated. Furthermore, the immune-related genes, i.e., the tumor necrosis factor (TNF-α), interleukin 8 (IL-8), transforming growth factor (TGF-β), and nuclear factor (NF-Kβ) were also up-regulated, and interleukin 10 (IL-10) was down-regulated. During the pre-challenge, sodium propionate and sodium butyrate seemed to bind the G-protein coupled receptor (grp40L), increasing its expression. During the challenge, citrate synthase (cs) was down-regulated, indicating that the SCFAs were used as an energy source to increase the immune and oxidative responses. Overall, our results suggest that sodium propionate and sodium butyrate may boost European sea bass immune response at the intestine level. [ABSTRACT FROM AUTHOR]

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Hepatocellular carcinoma (HCC), partly because of its complexity and high heterogeneity, has a poor prognosis and an extremely high mortality rate. In this study, mRNA sequencing expression profiles and relevant clinical data of HCC patients were gathered from different public databases. Kaplan–Meier survival curves as well as ROC curves validated that OLA1|CLEC3B was an independent predictor with better predictive capability of HCC prognosis compared to OLA1 and CLEC3B separately. Further, the cell transfection experiment verified that knockdown of OLA1 inhibited cell proliferation, facilitated apoptosis, and improved sensitivity of HCC cells to gemcitabine. In this study, the prognostic model of HCC composed of OLA1/CLEC3B genes was constructed and verified, and the prediction ability was favorable. A higher level of OLA1 along with a lower level of CEC3B is a sign of poor prognosis in HCC. We revealed a novel gene pair OLA1|CLEC3B overexpressed in HCC patients, which may serve as a promising independent predictor of HCC survival and an approach for innovative diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]

For the treatment of human immunodeficiency virus (HIV)-infected patients, the regular assessment of the immune status is indispensable. The quantification of CD4+ T lymphocytes in blood by gold standard optical flow cytometry is not point-of-care testing (POCT) compatible. This incompatibility is due to unavoidable pre-analytics, expensive and bulky optics with limited portability, and complex workflow integration. Here, we propose a non-optical, magnetic flow cytometry (MFC) workflow that offers effortless integration opportunities, including minimal user interaction, integrated sample preparation and up-concentration, and miniaturization. Furthermore, we demonstrate immunomagnetic CD4+ T lymphocyte labeling in whole blood with subsequent quantification using sheath-less MFC. Showing linearity over two log scales and being largely unimpaired by hematocrit, evidence is provided for POCT capabilities of HIV patients. [ABSTRACT FROM AUTHOR]

Objectives: Nontuberculous mycobacteria (NTM) bone and joint infections (BJIs) are uncommon. We evaluated the characteristics of BJIs and identified differences according to immune status. Methods: We performed a multicenter retrospective study in France involving patients with documented NTM BJI over a 9-year period. We collected the clinical and microbiological characteristics, management, and clinical outcomes of the patients. Results: Overall, 95 patients were included, of whom 50.5% (48/95) were immunosuppressed. Tenosynovitis was more frequent in the immunocompetent group, and native arthritis more common in the immunosuppressed group. Mycobacerium marinum and M. abscessus complex were significantly more frequent in the immunocompetent group, and M. avium and M. xenopi were significantly more frequent in the immunosuppressed group. The combination of antibiotherapy with surgery tended to be more frequent in the immunocompetent than the immunosuppressed group (63.8% (30/47) vs 47.8% (22/46), respectively); of the latter, 45.7% (21/46) received antimicrobial therapy alone, a higher frequency than in the immunocompetent group (23.4%, 11/47). The median duration of antimicrobial treatment was similar in the two groups (11 months). Mortality was significantly higher in the immunosuppressed group. Conclusions: Although the clinical presentations and the NTM species involved in BJI differed according to immune status, most recovered completely after treatment.

Studies have reported sex and age differences in self-rated health. On average, women rate their health as being poorer compared to men, and older individuals report poorer health than younger individuals. The current study evaluated sex and age differences for self-reported immune fitness, i.e. the capacity of the body to respond to health challenges (such as infections) by activating an appropriate immune response in order to promote health and prevent and resolve disease. Data from different survey studies (N = 8586) were combined for the current analyses. N = 8064 participants (93.3%) completed the single-item scale to assess momentary immune fitness (mean (Standard deviation, SD) age of 32.4 (16.7) years old, range: 18 to 103, 68.0% women) and N = 4263 participants (49.7%) completed the Immune Status Questionnaire (ISQ) to assess past year's immune fitness (mean (SD) age of 40.9 (17.1) years old, range: 18 to 103, 61.1% women). The analyses revealed that women rated their momentary and past year's immune fitness significantly lower than men (p

Abstract Background Heat stress has severe negative consequences on performance and health of pigs, leading to significant economic losses. The objective of this study was to investigate the effects of supplemental vitamin E and a botanical extract in feed or drinking water on growth performance, intestinal health, and oxidative and immune status in growing pigs housed under heat stress conditions. Methods Duplicate experiments were conducted, each using 64 crossbred pigs with an initial body weight of 50.7 ± 3.8 and 43.9 ± 3.6 kg and age of 13-week and 12-week, respectively. Pigs (n = 128) were housed individually and assigned within weight blocks and sex to a 2 × 4 factorial arrangement consisting of 2 environments (thermo-neutral (21.2 °C) or heat-stressed (30.9 °C)) and 4 supplementation treatments (control diet; control + 100 IU/L of D-α-tocopherol in water; control + 200 IU/kg of DL-α-tocopheryl-acetate in feed; or control + 400 mg/kg of a botanical extract in feed). Results Heat stress for 28 d reduced (P ≤ 0.001) final body weight, average daily gain, and average daily feed intake (−7.4 kg, −26.7%, and −25.4%, respectively) but no effects of supplementation were detected (P > 0.05). Serum vitamin E increased (P

Abstract Background Accurate prediction of tumor molecular alterations is vital for optimizing cancer treatment. Traditional tissue-based approaches encounter limitations due to invasiveness, heterogeneity, and molecular dynamic changes. We aim to develop and validate a deep learning radiomics framework to obtain imaging features that reflect various molecular changes, aiding first-line treatment decisions for cancer patients. Methods We conducted a retrospective study involving 508 NSCLC patients from three institutions, incorporating CT images and clinicopathologic data. Two radiomic scores and a deep network feature were constructed on three data sources in the 3D tumor region. Using these features, we developed and validated the ‘Deep-RadScore,’ a deep learning radiomics model to predict prognostic factors, gene mutations, and immune molecule expression levels. Findings The Deep-RadScore exhibits strong discrimination for tumor molecular features. In the independent test cohort, it achieved impressive AUCs: 0.889 for lymphovascular invasion, 0.903 for pleural invasion, 0.894 for T staging; 0.884 for EGFR and ALK, 0.896 for KRAS and PIK3CA, 0.889 for TP53, 0.895 for ROS1; and 0.893 for PD-1/PD-L1. Fusing features yielded optimal predictive power, surpassing any single imaging feature. Correlation and interpretability analyses confirmed the effectiveness of customized deep network features in capturing additional imaging phenotypes beyond known radiomic features. Interpretation This proof-of-concept framework demonstrates that new biomarkers across imaging features and molecular phenotypes can be provided by fusing radiomic features and deep network features from multiple data sources. This holds the potential to offer valuable insights for radiological phenotyping in characterizing diverse tumor molecular alterations, thereby advancing the pursuit of non-invasive personalized treatment for NSCLC patients.

Cellular immunity plays an important role in the control of SARS-CoV-2. Lymphopenia and a decrease in the functional activity of cells may be among the main reasons for deterioration of clinical outcomes of the disease. Usage of the bacterial therapeutic vaccine Immunovac-VP-4 during the inflammation phase may be promising for immunomodulation of the cellular immunity. The aim of our study was to evaluate the dynamics of lymphocyte subpopulations in hospitalized patients with COVID-19 upon combining the basic therapy with immunotropic drug based on the antigens from opportunistic pathogens. The study included 45 patients (18-70 years old) admitted with a confirmed diagnosis of moderate/severe infection caused by the COVID-19 virus. In addition to basic therapy, 33 persons of this group received Immunovac-VP-4 by a combined nasal-oral method. Subpopulation activity of peripheral blood lymphocytes in patients over time (at baseline, on the 14th and 30th day after hospitalization) was studied by flow cytometry by means of FC-500 Cytomics (Beckman Coulter, USA) using monoclonal antibodies (mAb) (Immunotech, France). In the group receiving only standard therapy, an increased number of T lymphocytes was detected on day 14 (79.9 (75.5-81.6), p = 0.00252), on day 30 from the start of treatment (78.4 (74.25-79. 2), p = 0.03662), and a decrease in B lymphocytes on day 14 (10.6 (7.78-11.63), p = 0.03236), on day 30 (7.85 (6.25-11.1), p = 0.01352) relative to baseline parameters upon admission. We revealed more pronounced changes in the parameters of cellular immunity relative to the initial parameters, i.e., an increased proportion of T lymphocytes on the 14th day (80.1 (73.8-84.2), p = 0.00018), and 30th day from starting the treatment (80.2 (76-81.9)), T helpers at 14 days after treatment (50.2 (43-57), p = 0.00694), cytotoxic T cells by 30th day of therapy (26.35 (24-29.4), p = 0.0114), decrease in B lymphocytes on day 14 (13.1 (8.2-16.9), p = 0 00158), on the 30th day from the start of treatment (8.2 (7.6-9.7), p

A 9-week experiment investigated the effects of dietary cobalt levels on the growth performance, antioxidant capacity, and immunity of largemouth bass. Six feed groups were designed and each group received different cobalt levels, including 0.129 mg/kg (control group), 0.192 mg/kg, 0.201 mg/kg, 0.233 mg/kg, 0.277 mg/kg, and 0.316 mg/kg. The results show that the control group (0.129 mg/kg diet) had the lowest final body weight (FBW), weight gain rate (WGR), and specific growth rate (SGR), and the highest feed conversion ratio (FCR), when compared to the cobalt supplementation groups. Dietary cobalt levels of 0.192 mg/kg increased the body protein content and decreased the body moisture content. Regarding antioxidant capacity, the highest catalase (CAT) activity was found in the 0.277 mg/kg dietary cobalt group, while the malondialdehyde (MDA) content was significantly diminished; the total antioxidant capacity (T-AOC) content and glutathione peroxidase (GSH-Px) activity exhibited the highest values in the 0.192 mg/kg and 0.233 mg/kg dietary cobalt groups, respectively. Regarding gene expression, compared with the control group, the mRNA expression of sod was upregulated in the 0.192 mg/kg, 0.233 mg/kg, and 0.277 mg/kg dietary cobalt groups, while the mRNA expression of gpx was diminished when dietary cobalt levels were below 0.233 mg/kg. In addition, the highest il-10 and tgf-β mRNA expression levels were observed in the 0.201 mg/kg and 0.233 mg/kg dietary cobalt groups, respectively. According to the quadratic regression analysis based on the SGR and FCR, the optimal requirement was 0.24 and 0.26 mg/kg of dietary cobalt, respectively.

Background: Cytomegalovirus (CMV) gastrointestinal (GI) diseases impact both immunocompromised and immunocompetent individuals, yet comprehensive studies highlighting the differences between these groups are lacking. Methods: In this retrospective study (January 2000 to July 2022) of 401 patients with confirmed CMV GI diseases, we categorized them based on immunological status and compared manifestations, treatments, outcomes, and prognostic factors. Results: The immunocompromised patients (n = 193) showed older age, severe illnesses, and higher comorbidity rates. GI bleeding, the predominant manifestation, occurred more in the immunocompetent group (92.6% vs. 63.6%, p = 0.009). Despite longer antiviral therapy, the immunocompromised patients had higher in-hospital (32.2% vs. 18.9%, p = 0.034) and overall mortality rates (91.1% vs. 43.4%, p < 0.001). The independent factors influencing in-hospital mortality in the immunocompromised patients included GI bleeding (OR 5.782, 95% CI 1.257–26.599, p = 0.024) and antiviral therapy ≥ 14 days (OR 0.232, 95% CI 0.059–0.911, p = 0.036). In the immunocompetent patients, age (OR 1.08, 95% CI 1.006–1.159, p = 0.032), GI bleeding (OR 10.036, 95% CI 1.183–85.133, p = 0.035), and time to diagnosis (OR 1.029, 95% CI 1.004–1.055, p = 0.021) were significant prognostic factors, with the age and diagnosis time cut-offs for survival being 70 years and 31.5 days, respectively. Conclusions: GI bleeding is the most common manifestation and prognostic factor in both groups. Early diagnosis and effective antiviral therapy can significantly reduce in-hospital mortality. [ABSTRACT FROM AUTHOR]

Hypoxia‐inducible factor (HIF) pathway genes influence tumorigenesis and immune status. However, the associations between genetic variants in hypoxia‐related genes and colorectal cancer risk and the immune status of hypoxia‐associated genes in colorectal cancer have not been systematically characterized. The associations between genetic variants and colorectal cancer risk were evaluated in Chinese, Japanese and European populations using logistic regression analysis. The relationships between target genes and tumour immune infiltration were predicted by Tumour Immune Estimation Resource (TIMER). We found that rs34533650 in EPAS1 was associated with colorectal cancer risk (OR = 1.43, 95% CI = 1.20–1.70, P(FDR) = 8.35 × 10−4), and this finding was validated in two independent populations (Japanese: OR = 1.07, 95% CI = 1.01–1.15, p = 3.38 × 10−2; European: OR = 1.11, 95% CI = 1.03–1.19, p = 6.04 × 10−3). EPAS1‐associated genes were enriched in immune‐related pathways. In addition, we found that EPAS1 copy number variation (CNV) was associated with the degree of infiltration of immune cells and observed correlations between EPAS1 expression and immune cell infiltration levels in colorectal cancer. These results highlight that genetic variants of hypoxia‐related genes play roles in colorectal cancer risk and provide new insight that EPAS1 might be a promising predictor of colorectal cancer susceptibility and immune status. [ABSTRACT FROM AUTHOR]

Background: The hepatitis B virus (HBV) is one of the most important biological occupational hazards for healthcare workers. A high percentage of HBV infections are attributable to percutaneous occupational exposure. This study aimed to describe the HBV immunisation and current immune status of all the nurses employed in a regional hospital in central South Africa. Methods: A descriptive record review included all the nurses (N = 388) employed in a regional hospital in central South Africa from 01 January 2018 to 31 January 2020. A total of 289 health records were included in the study. Data were analysed using descriptive statistics. Logistic regression analysis was used to establish factors associated with full immunisation. Results: Most nurses were females (87.9%), working in medical (27.0%) wards. Only 20.4% of nurses received one dose of vaccine, while 51.2% received the three prescribed doses. However, 91.2% of nurses did not receive the vaccine at the correct intervals. Most of the tested nurses (71.0%) were immune. Immunisation status was significantly associated with religion (p 0.001) and schedule (p = 0.003). Nurses who were non-Christians were 35.9% less likely to be fully vaccinated compared to Christians. Conclusion: Half of the nursing staff received three doses as prescribed. All nurses should receive the vaccine against HBV and their immune status monitored to minimise the risk of an infection. It is therefore recommended that proof of immunity should be a requirement. Contribution: This study found a high percentage of nurses with HBV antibodies, which will ensure workplace safety.

Occupational hazards affect immunological reactivity and increase the risk of infection with respiratory pathogens. The purpose of our work was to study the mechanisms and causes of developing carriage of streptococci possessing genetic determinants of resistance to antibiotics as health risk factors for workers engaged in coke production and basic oxygen steelmaking. We examined 136 workers of a ferrous metals industry and compared the prevalence of the carriage of Streptococcus pneumoniae, Streptococcus spp. and macrolide resistance genes (Mef, ErmB) in those engaged in coke production and basic oxygen steelmaking. We also collated the results of immunological examination of the carriers and non-carriers of S. pneumoniae. The control cohort was formed of engineering and technical personnel. We established that, compared with the controls, Streptococcus pneumoniae was a more frequent finding in the workers engaged in coke production and basic oxygen steelmaking (p ˂ 0.05). The cycle threshold value of Streptococcus spp. in them was also statistically higher. The Mef gene was more abundant in the steelmakers, including those carrying Streptococcus pneumoniae (p ˂ 0.05), and a change in immunological reactivity was detected in the cases carrying Streptococcus pneumoniae. In those engaged in basic oxygen steelmaking, significant changes were detected at the cellular level expressed by a reduced absolute number of mature T-lymphocytes (CD3+), T-helpers (CD4+), and T-suppressor/cytotoxic cells (CD8+) (p ≤ 0.05). At the humoral level, both the relative and absolute number of B-lymphocytes (CD19+) and the level of IgM were reduced, while that of IgG was, on the opposite, increased (p ≤ 0.05). In the coke plant workers carrying Streptococcus pneumoniae, the level of IgG was significantly higher than the control and reference values. We conclude that Streptococcus pneumoniae carriage in the steelmakers as a health risk factor was accompanied by a change in immunological reactivity and higher abundance of the Mef gene compared to the controls while in the coke production workers the related differences were detected only in the IgG level.

Lavender essential oil (LVEO) (Lavandula angustifolia L) was investigated for its impacts on broiler chicken growth, intestinal histomorphology, blood biomarkers, and immunological status. Four hundred 3-days-old male chicks (ROSS 308 broilers) (91.47 ± 0.15 g) were randomised to receive four test groups and nourished on basal diets having four levels of LVEO: 0, 200, 400, and 600 mg Kg−1 over 35 days. Dietary addition of LVEO linearly increased the body weight and weight gain during the grower period, while its addition did not affect the overall growth performance. Dietary LVEO increased the villous height, and the higher villous height was detected in the LVEO600 group. Dietary LVEO increased cluster of differentiation (CD3 and CD20) immunoexpression within the spleens of birds given LVEO400 and LVEO600 diets. Serum triiodothyronine and thyroxine hormone levels were the highest in the LVEO400 and LVEO600 groups. LVEO supplementation raised serum growth hormone levels in a dosage-dependent manner. The serum concentrations of glucose and leptin hormone did not vary significantly between the LVEO-supplemented and LVEO0 groups. All levels of supplemental LVEO diminished serum cholesterol, triglyceride, and low-density lipoprotein cholesterol levels, while raising the high-density lipoprotein cholesterol concentration. Total protein values were augmented in all LVEO groups, with the highest concentrations of albumin and globulin in the LVEO600 group, followed by the LVEO400 group. Supplemental LVEO increased serum concentration of complement 3, interleukin-10, and lysozyme activity in a level-dependent manner. Modifications in the birds’ physiological activities, blood biochemical, intestinal morphological characteristics, and immunological status support the conclusion that dietary LVEO supplementation had numerous positive effects. However, it didn’t influence the birds’ growth.

This experiment investigated the effects of the brooding system (BS) and stocking density (SD) on the immune response of 1-14-day-old broiler chicks. A 3672 one-day-old Cobb 500 chicks were raised in two BSs (conventional floor brooding system (CFBS) and the newly developed multi-tier closed brooding system (NDBS)) at four different SDs (30, 60, 90, and 120 chicks/m2), resulting in a 2 × 4 factorial arrangement. Immunity data on lymphoid organ weights, maternal antibody titres to IBV, IBDV, and NDV, and stress indicators were collected on days 6 and 12. The results showed that CFBS and NDBS had similar effects on the relative development of chick lymphoid organs (Bursa, spleen, and thymus), the durability of the maternal humoral immune response against IBDV, and the maintenance of normal levels of stress indicators. Birds in CFBS outperformed NDBS in terms of the durability of maternal immunity to IBV and NDV. Birds in NDBS had a higher liver weight percentage than CFBS. Maternal immunity, lymphoid organ weights %, glucose and cholesterol concentrations were not altered by SD. In contrast to relative weights, differences in absolute lymphoid weights (g) were attributed to differences in live weights. An increase in SD per area unit resulted in an increase in heterophils and a decrease in lymphocyte percentage resulted in an increase in the ratio of heterophils to lymphocytes(H:L). In conclusion, birds in the higher SD had lower live weights and higher H:L ratios. Smarter brooding systems are needed to usher in a new era for the poultry industry.Highlights The brooding system and/or stocking density accounted for the stress factors of the birds. Both brooding systems increased the relative development of chick lymphoid organs and the durability of the maternal humoral immune response to IBDV. Smarter brooding systems are needed to apply the critical control point standard and usher in a new era for the poultry industry. As stocking density per unit area increased, live and liver weights decreased, and the lymphocyte ratio increased.

According to the WHO data, the number of infected people exceeded 765.2 million people during the COVID-19 pandemic. The severity of patient’s condition is determined by immune system hyperactivation. Activation of T- and B-lymphocyte subsets plays a prominent role in the control of infectious process. A content of small circular DNA molecules — T-cell receptor excision circles (TREC — T-cell receptor excision circles) and B-cell (“kappa”) excision rings (KREC — Kappa-deleting recombination excision circles) — in the peripheral blood can be used as a marker of the functionally active T and B cells maturation. The purpose of this work is to quantify peripheral blood TREC and KREC level in patients with the new coronavirus infection COVID-19 of varying severity.Materials and methods.The material consisted of 1028 blood samples from patients with a confirmed diagnosis of COVID-19, as well as 717 blood samples from apparently healthy volunteers. The content of TREC and KREC DNA fragments in the total DNA fraction was assessed by quantitative Real-time PCR using the “TREC/KREC-AMP PS” test system (St. Petersburg Pasteur Institute, Russia). Blood cell phenotyping was carried out using flow cytometry.Results.TREC/KREC levels were significantly reduced in COVID-19 patients (p 0.0001 at 95% CI). A significant direct correlation was established between the levels of peripheral blood TREC molecules and level of CD45+CD3+CD19–T cells (r = 0.59, p 0.0001), as well as between KREC level and count of CD45+CD3–CD19+B cells (r = 0.66, p 0.0001). The level of TREC molecules in patients with severe vs. moderate infection was significantly reduced in patients aged 30–39 years old (p = 0.0404) and 40–49 years old (p = 0.0356). The negative correlation between severity of COVID-19 clinical manifestations and TREC level in the blood of patients in 30–49 year age group indicates about an opportunity of using this analyte as a diagnostic and prognostic laboratory marker of patient’s condition. A simple PCR analysis algorithm makes it relevant to use the described method for assessing a state of immunity in coronavirus patients in the context of systemic negative impact of the SARS-CoV-2 virus on human organism.

In 2018, classical swine fever (CSF) reemerged in Gifu Prefecture, Japan, after 26 years of absence, and vaccination of domestic pigs using a live attenuated vaccine was initiated in 2019. Because the vaccine efficacy in piglets is influenced by the maternal antibody levels, vaccination should be administered at the optimal age by assuming the antibody level in sows. In this study, the shift in the antibody titer distribution in sows due to the initiation of vaccination to naïve herds and its influence on the vaccine-induced immunity rate in fattening pigs were investigated for 3 years. The results indicated that higher antibody titers were induced in first-generation sows after vaccine initiation because they were immunologically naïve, but the distribution of antibody titers shifted to lower levels along with their replacement with second-generation sows. The average vaccination age of fattening pigs became earlier year by year, and the vaccine-induced antibody rate was almost ≥80%. Based on the estimation of the optimal age for vaccination, it was found that vaccination at a younger age may reduce the risk of CSF infection. Taken together, the risk of CSF outbreaks can be reduced by administering vaccines at the optimal age based on the sequential monitoring of the sow’s immune status.

In order to evaluate the effects of acidifiers and essential oils in drinking water on growth, intestinal digestive capacity, and immune status in broilers, a total of 480, 1-day-old Arbore Acres broilers were randomly assigned to four treatments including normal tap water (Ctr) and tap water supplemented with acidifier I (ACI), acidifier I and essential oils (ACI+EO), and acidifier II (ACII). Both ACI+EO and ACII increased final body weight. The pH value of the crop and gizzards was reduced by ACI+EO, and ACII decreased the pH values of the proventriculus and gizzards (p < 0.05). Compared with control group, ACI, ACI+EO, ACII significantly enhanced lipase activity in jejunum but ACII decreased the level of serum total cholesterol and total triglyceride (p < 0.05). Compared with the control group, ACI+EO and ACII significantly increased the relative weight of the spleen, increased the level of serum IgA and IgM, and decreased E. coli in excreta, while ACII significantly decreased Salmonella in excreta (p Lactobacillus in excreta. In conclusion, ACI+EO improved immune status and ACII was effective in reducing Salmonella and promoting Lactobacillus, contributing to intestinal health.

The purpose of the current study was to assess the effects of substituting corn with ground brown rice on growth performance, immune status, and gut microbiota in weanling pigs. Seventy-two weanling pigs (28 d old with 6.78 ± 0.94 kg body weight [BW]) were randomly allotted to two dietary treatments with six pens and six pigs (three barrows and gilts) per pen within a randomized complete block design. The control pigs were fed a typical diet for weanling pigs based on corn and soybean meal diet (control diet: CON), and the other pigs were fed a formulated diet with 100% replacement of corn with ground brown rice for 35d (treatment diet: GBR). Growth performance, immune status, and gut microbiota of weanling pigs were measured. The substitution of corn with GBR did not affect growth performance or diarrhea frequency. Additionally, there were no differences in white blood cell number, hematocrit, cortisol, C-reactive protein, and serum tumor necrosis factor-alpha levels between pigs fed CON or GBR for the first 2 wk after weaning. However, weanling pigs fed GBR had lower (P < 0.05) serum transforming growth factor-beta 1 level than those fed CON. Furthermore, weanling pigs fed GBR had increased (P < 0.05) relative abundance of phylum Firmicutes and genus Lactobacillus and Streptococcus and decreased (P < 0.05) relative abundance of phylum Bacteroidetes and genus Clostridium and Prevotella in the gut microbiota compared with those fed CON. In conclusion, there was no significant difference in growth performance when corn was replaced with ground brown rice in diets for weanling pigs. Furthermore, the substitution of corn with ground brown rice in weaning diet modulated immune status and gut microbiota of pigs by increasing beneficial microbial communities and reducing harmful microbial communities. Overall, ground brown rice-based diet is a potential alternative to corn-based diet without negative effects on growth performance, immune status, and gut microbiota changes of weanling pigs.

Yangjin Huang,&ast; Jun Xu,&ast; Chunming Xie, Yuejuan Liao, Rong Lin, Yuan Zeng, Fujun Yu Department of Gastroenterology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fujun Yu; Yuan Zeng, Tel/Fax +86 577-555791922, Email yufujun@wmu.edu.cn; zengyuan121388@163.comBackground: Hepatocellular carcinoma (HCC), one of the commonest cancers at present, possesses elevated mortality. This study explored the predictive value of CSTF2/PDE2A for HCC prognosis.Methods: In this study, clinical information and RNA sequencing expression profiles of HCC patients were acquired from common databases. Kaplan–Meier curve compound with time-dependent ROC curve, nomogram model, and univariate/multivariate Cox analysis were carried out to access the prediction capacity of CSTF2/PDE2A. The immune status, tumor microenvironment, drug sensitivity, biological function and pathway between HCC and adjacent non-tumorous tissue were analyzed and compared. Finally, RT-qPCR, Western blot, and apoptosis assays were performed to verify the effect on HCC cells of CSTF2/PDE2A.Results: The optimal cut-off value of CSTF2, PDE2A and CSTF2/PDE2A was 6.95, 0.95 and 3.63, respectively. In TCGA and ICGC cohorts, the high group of CSTF2/PDE2A presented higher OS compared to low group. The area under the curve (AUC) for OS at 1-, 2-, and 3-years predicted by CSTF2/PDE2A were 0.731/0.695, 0.713/0.732 and 0.689/0.755, higher than the counterparts of the single gene CSTF2 and PDE2A. Multivariate Cox analysis revealed that CSTF2/PDE2A (HR = 1.860/3.236, 95% CI = 1.265– 2.733/1.575– 6.645) was an independent prognostic factor for HCC. The OS nomogram model created according to five independent factors including CSTF2/PDE2A showed excellent capacity for HCC prognosis. Furthermore, the immune status of the CSTF2/PDE2A high group was deleted, cell cycle-related genes and chemotherapy resistance were increased. Finally, cell experiments revealed distinct differences in the proliferation, apoptosis, protein and mRNA expression of HCC cells after si-CSTF2 transfection compared with the negative control.Conclusion: Taken together, the gene pair CSTF2/PDE2A is able to forecast the prognosis of HCC and regulates cell cycle, which is promising as a novel prognostic predictor of HCC.Keywords: hepatocellular carcinoma, gene pair, overall survival, cell cycle, immune status, prognosis

The study was planned on 120 one-day-old broiler chickens, randomly distributed into 5 dietary treatments with 3 replicates having eight chickens each. Control birds (CON) were reared under thermoneutral conditions and offered a basal diet to meet their nutrient requirements. Treatment CS was offered the basal diet under cold stress. While, treatments ZNC100, CR2, and ZN+CR were offered basal diet under cold stress, supplemented with organic Zinc, organic Chromium or their combinations at 100, 2, or 100 + 2 mg/kg DM, respectively. Birds under CS treatment had higher feed intake compared to other treatments. Body weight gain and feed conversion ratio were not significantly affected by treatments. Digestibility of dry matter, crude protein, and nitrogen-free extra of birds under CON treatment were greater than CS, ZNC100, and CR2 treatments. The concentration of blood urea nitrogen and albumin to globulin ratio in CS treatment was higher compared to CON treatment. The antibody response of 21-day-old-broiler chickens in the CS group was lower than the birds of the ZN+CR group. The lowest activities of glutathione peroxidase and superoxide dismutase were found in the blood serum of the CS group. The percentage of dressing carcass in both CON and CS treatments were lower than those of birds under ZN+CR treatment. Moreover, the yield of breast and drumstick of the ZN+CR treatment was higher (P < 0.05) than the CON treatment. There was better production performance along with improved immune status in broiler birds fed a diet supplemented with organic Zinc and Chromium alone or their combination under cold stress.

Background: Limited research has been conducted on the impact of rituximab on immune function and the incidence of side effects in children undergoing combination chemotherapy for aggressive mature B-cell lymphoma/leukemia. Methods: Clinical data from 85 patients with primary pediatric aggressive mature B-cell lymphoma/leukemia, treated according to the Chinese Children's Cancer Group (CCCG)-mature B-cell non-Hodgkin lymphoma (BNHL)-2015 protocol from June 1, 2015, to December 1, 2022, were collected from three tertiary medical centers in China. Patients with pre-existing malignancies or primary immune deficiencies (PIDs) were excluded. Results: Between June 1, 2015, and December 1, 2022, 85 patients (65 [76.5%] boys and 20[23.5%] girls; mean age, 6.95 years) were enrolled, and immune data at baseline during follow-up were analyzed. At the end of chemotherapy, a higher proportion of patients in the R4 group exhibited a decrease in peripheral blood CD3− CD19+ B cells (20[100%] of 20 vs 13[47.8%] of 18, p = 0.04), CD3+ T cells (21[91.3%] of 23 vs 14[60.9%] of 23, p = 0.016), and serum IgM (14[60.9%] of 23 vs 4[17.4%] of 23, p = 0.003) compared to the R3 group. However, these differences were no longer statistically significant six months after chemotherapy administration. The combination of rituximab with AA was associated with a higher incidence of significant thrombocytopenia (49[81.7%] of 60 vs 29[52.7%] of 55, p = 0.001) and infection (35[58.3%] of 60 vs 17[30.9%] of 55, p = 0.003) compared to AA alone. Furthermore, the combination of rituximab with BB was linked to a higher incidence of significant thrombocytopenia (32[52.5%] of 61 vs 31[31.0%] of 100, p = 0.007) compared to BB alone. Conclusions: While the effects of rituximab in combination with intense chemotherapy for childhood aggressive mature B-cell lymphoma/leukemia on children's immune function generally recovers within six months it may still prolong the recovery from immunoglobulinemia, posing a risk of secondary infections. Further studies are required to identify children with potential primary immunodeficiencies.