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Conventionally, megakaryocytes (MKs) are regarded as platelet-producing cells and their platelet-related functions in haemostasis have been well documented. However, it is increasingly evident that MKs have functions beyond platelet production. Convincing findings suggest that MKs are active participants in immunity and infections. Many reviews in the published literature have examined the immune functions of MK-derived platelets. However, relatively few reviews have emphasised on the role of MKs as immune cells. This review gives an overview of MKs, megakaryopoiesis and thrombocytopoiesis, as well as a thorough examination of the evidence that favours MKs as immune cells. The emerging and multifaceted contributions of MKs to host defence against various infections are also discussed. Together, these findings identify MKs as key players in both immune homeostasis and host-pathogen interactions, presenting new therapeutic opportunities. [ABSTRACT FROM AUTHOR]

The primary objective of this study was to evaluate the radioprotective effects of Flavonoids Extracted from Jatropha curcas Leaves (FEL) and to elucidate the underlying protective mechanisms against radiation damage. Six monomers of the FEL were analyzed using Ultra Performance Liquid Chromatography (UPLC). The results indicate that FEL increases the survival rate of mice and promotes the recovery of organs damaged by 60Co γ-rays to their normal appearance, through mechanisms that include the enhancement of immune and hematopoietic functions in vivo. In vitro studies suggest that the molecular mechanism by which FEL mitigates radiation damage involves the reduction of DNA damage and mutations. These findings indicate that FEL could be effective in alleviating radiation-induced injuries.

Oligodendrocyte precursor cells (OPCs) have long been regarded as progenitors of oligodendrocytes, yet recent advances have illuminated their multifaceted nature including their emerging immune functions. This review seeks to shed light on the immune functions exhibited by OPCs, spanning from phagocytosis to immune modulation and direct engagement with immune cells across various pathological scenarios. Comprehensive understanding of the immune functions of OPCs alongside their other roles will pave the way for targeted therapies in neurological disorders. [ABSTRACT FROM AUTHOR]

Abstract Background DNA methylation has been documented to play vital roles in diseases and biological processes. In bovine, little is known about the regulatory roles of DNA methylation alterations on production and health traits, including mastitis. Results Here, we employed whole-genome DNA methylation sequencing to profile the DNA methylation patterns of milk somatic cells from sixteen cows with naturally occurring Staphylococcus aureus (S. aureus) subclinical mastitis and ten healthy control cows. We observed abundant DNA methylation alterations, including 3,356,456 differentially methylated cytosines and 153,783 differential methylation haplotype blocks (dMHBs). The DNA methylation in regulatory regions, including promoters, first exons and first introns, showed global significant negative correlations with gene expression status. We identified 6435 dMHBs located in the regulatory regions of differentially expressed genes and significantly correlated with their corresponding genes, revealing their potential effects on transcriptional activities. Genes harboring DNA methylation alterations were significantly enriched in multiple immune- and disease-related pathways, suggesting the involvement of DNA methylation in regulating host responses to S. aureus subclinical mastitis. In addition, we found nine discriminant signatures (differentiates cows with S. aureus subclinical mastitis from healthy cows) representing the majority of the DNA methylation variations related to S. aureus subclinical mastitis. Validation of seven dMHBs in 200 cows indicated significant associations with mammary gland health (SCC and SCS) and milk production performance (milk yield). Conclusions In conclusion, our findings revealed abundant DNA methylation alterations in milk somatic cells that may be involved in regulating mammary gland defense against S. aureus infection. Particularly noteworthy is the identification of seven dMHBs showing significant associations with mammary gland health, underscoring their potential as promising epigenetic biomarkers. Overall, our findings on DNA methylation alterations offer novel insights into the regulatory mechanisms of bovine subclinical mastitis, providing further avenues for the development of effective control measures. Graphical Abstract

Background. The Coccomyxa sp. strain KJ (Coccomyxa KJ), a microalga found in Japan, has a potential function in controlling viral infections. Recently, its dry powder has been marketed as a health food product. Objectives. This pilot study investigated the effects of Coccomyxa KJ powder tablet intake on allergic reactions and immune functions in healthy participants. Materials and methods. Nine healthy volunteers (4 males and 5 females) who expressed interest in foods containing Coccomyxa KJ, and were willing to undergo blood tests, were recruited. Each individual was asked to take 2 Coccomyxa KJ powder tablets (0.3 g) before breakfast once a day for 4 weeks. The salivary immunoglobulin A (IgA) level and blood parameters (white blood cell (WBC) count, eosinophil and lymphocyte counts and percentages, natural killer (NK) cell activity, interleukin (IL)-6 level, and T helper (Th)1/Th2 cell ratio) were evaluated at baseline and weeks 2 and 4. Results. The 4-week intake of Coccomyxa KJ did not affect salivary IgA levels, WBC count, eosinophil and lymphocyte counts and percentages, or the Th1/Th2 ratio. There were significant differences in the NK cell activity after 4 weeks, with an average increase of 11.78 (95% confidence interval (95% CI): 6.80-16.76). None of the patients experienced adverse reactions during or after the study. Conclusions. Long-term Coccomyxa KJ intake improved NK cell activity without causing adverse effects on the indicators of local immunity, systemic inflammation and immune response balance. This study suggests that Coccomyxa KJ powder tablets can induce beneficial immune modifications without causing any adverse effects. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper addresses the various sources of Se in the aquatic environment as well as the positive and negative effects on fish. It emphasizes that optimal dietary Se levels are necessary for healthy biological processes in fish, such as growth, reproduction, and immunity. Since organic Se appears to be the most ideal for fish due to its low toxicity, environmental safety, and efficient fish culture, it explores the potential sources and forms of Se. Extreme doses could be toxic to fish, and higher levels could cause retarded growth, survival issues, abnormalities, and poor performance. However, adverse effects depend on the acceptance of the fish species. Additionally, there are a number of biological techniques that may be used to remove excess Se from the aquatic environment, with phytoremediation being the most effective. The production of Se-rich feeds and their benefits for fish immune systems, disease prevention, and growth development are discussed in this article. These factors contribute to the profitability of fish farmers and their confidence in the feed industry. In order to monitor and study Se's effects on fish and their aquatic environment, the report highlights the significance of the feed industry and how it connects farmers with research institutions. Dietary selenium (Se) is an essential component that supports fish growth and the immune system. This review attempts to provide insight into the biological impacts of dietary Se, including immunological responses, infection defense, and fish species growth, and it also identifies the routes via which it enters the aquatic environment. Dietary Se is important in fish feed due to its additive, antioxidant, and enzyme properties, which aid in various biological processes. However, excessive intake of it may harm aquatic ecosystems and potentially disrupt the food chain. This review explores the diverse natures of dietary Se, their impact on fish species, and the biological methods for eliminating excesses in aquatic environments. Soil has a potential role in the distribution of Se through erosion from agricultural, industrial, and mine sites. The research on dietary Se's effects on fish immune system and growth can provide knowledge regarding fish health, fish farming strategies, and the health of aquatic ecosystems, promoting the feed industry and sustainable aquaculture. This review provides data and references from various research studies on managing Se levels in aquatic ecosystems, promoting fish conservation, and utilizing Se in farmed fish diets. [ABSTRACT FROM AUTHOR]

Enzyme is a kind of protein generated by living cells in body, with highly catalytic performance. There are thousand and thousands of enzymes in our body, forming a powerful enzyme network system, which is coordinating and controlling body bioactivities, this ensures life or cell activities going in a precise processes, which can make cell material metabolism process orderly in the body, and make material metabolism, energy metabolism and normal physiological activities adapt to each other, as well as closely related to immune system, immune organs, immune cells and cell function balance. Enzyme balance in immune cells directly or indirectly affects the function of immune system and constitutes the key point of enzyme immune balance. [ABSTRACT FROM AUTHOR]

Staphylococcus chromogenes (SC) is a common coagulase-negative staphylococcus described as an emerging mastitis pathogen and commonly found in dairy farms. This study investigated the potential involvement of DNA methylation in subclinical mastitis caused by SC. The whole-genome DNA methylation patterns and transcriptome profiles of milk somatic cells from four cows with naturally occurring SC subclinical mastitis (SCM) and four healthy cows were characterized by next-generation sequencing, bioinformatics, and integration analyses. Comparisons revealed abundant DNA methylation changes related to SCM, including differentially methylated cytosine sites (DMCs, n = 2,163,976), regions (DMRs, n = 58,965), and methylation haplotype blocks (dMHBs, n = 53,098). Integration of methylome and transcriptome data indicated a negative global association between DNA methylation at regulatory regions (promoters, first exons, and first introns) and gene expression. A total of 1486 genes with significant changes in the methylation levels of their regulatory regions and corresponding gene expression showed significant enrichment in biological processes and pathways related to immune functions. Sixteen dMHBs were identified as candidate discriminant signatures, and validation of two signatures in more samples further revealed the association of dMHBs with mammary gland health and production. This study demonstrated abundant DNA methylation changes with possible involvement in regulating host responses and potential as biomarkers for SCM. [ABSTRACT FROM AUTHOR]

COP9 constitutive photomorphogenic homolog subunit 5 (COPS5), also known as Jab1 or CSN5, has been implicated in a wide variety of cellular and developmental processes. By analyzing male germ cell–specific COPS5-deficient mice, we have demonstrated previously that COPS5 is essential to maintain male germ survival and acrosome biogenesis. To further determine the role of Cops5 in peritubular myoid cells, a smooth muscle lineage surrounding seminiferous tubules, we herein derived mice conditionally deficient for the Cops5 gene in smooth muscle cells using transgenic Myh11 -Cre mice. Although these conditional Cops5 -deficient mice were born at the expected Mendelian ratio and appeared to be normal within the first week after birth, the homozygous mice started to show growth retardation after 1 week. These mice also exhibited a variety of developmental and reproductive disorders, including failure of development of reproductive organs in both males and females, spermatogenesis defects, and impaired skeletal development and immune functions. Furthermore, conditional Cops5 -deficient mice revealed dramatic impairment of the endocrine system associated with testicular functions, including a marked reduction in serum levels of gonadotropins (follicle-stimulating hormone, luteinizing hormone), testosterone, insulin-like growth factor 1, and glucose, but not vasopressin. All homozygous mice died before age 67 days in the study. Collectively, our results provide novel evidence that Cops5 in smooth muscle lineage plays an essential role in postnatal development and reproductive functions. [ABSTRACT FROM AUTHOR]

An inadequate stress response is associated with impaired neuroimmunoendocrine communication, increasing morbidity and mortality. Since catecholamines (CA) constitute one of the acute stress response pathways, female mice with an haploinsufficiency of the tyrosine hydroxylase gene (TH-HZ), the main limiting enzyme in CA synthesis, show low CA amounts, exhibiting an impairment of homeostatic systems. The aim of this study was to investigate the effect of a punctual stress in TH-HZ mice, determining the differences with wild-type (WT) mice and those due to sex by restraint with a clamp for 10 min. After restraint, a behavioral battery was performed, and several immune functions, redox state parameters, and CA amounts were evaluated in peritoneal leukocytes. Results show that this punctual stress impaired WT behavior and improved female WT immunity and oxidative stress, whereas in TH-HZ mice, all parameters were impaired. In addition, different responses to stress due to sex were observed, with males having a worse response. In conclusion, this study confirms that a correct CA synthesis is necessary to deal with stress, and that when a positive stress (eustress) occurs, individuals may improve their immune function and oxidative state. Furthermore, it shows that the response to the same stressor is different according to sex. [ABSTRACT FROM AUTHOR]

The establishment of chronic oxidative and inflammatory stress with aging leads to the deterioration of the nervous and immune systems and, consequently, to the loss of health. The aim of this work was to study the effect of exposure to low-frequency pulsed electromagnetic fields (PEMFs) produced by the NEURALTER® system (15 min/day for 4 weeks) in the behavior, immune functions, and oxidative and inflammatory state of old mice. Female old CD1 mice were divided into three groups: control group, handling control group and Neuralter group. Then, behavioral tests were performed, and peritoneal leukocytes were extracted to analyze function, oxidative and inflammatory parameters. In peritoneal leukocytes from old mice, the effects in vitro of 15 min with NEURALTER® were studied on function and oxidative parameters. The results show that after this type of treatment, old mice had greater coordination and locomotion, better immune function, and an oxidative-inflammatory state. Similarly, the immune function and oxidative state of leukocytes showed an improvement when these cells were exposed directly to the NEURALTER® system. In conclusion, the exposure to low-frequency PEMFs produced by the NEURALTER® system has beneficial effects on health in aging. In addition, this effect is direct, at least in part, on immune cells. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that royal jelly (RJ) has exceptional biological properties, and that major royal jelly proteins (MRJPs) are the key active factors in RJ. The objective of this study was to compare the difference in the protein content between RJ and MRJPs using non-labeled, quantitative proteomics technology, and to investigate the adjustment features and mechanisms of MRJPs on murine immune functions and the composition of intestinal flora in cyclophosphamide-treated mice. Results showed that, during the process of extracting MRJPs, the ratio of the protein types in the main protein and other proteins decreased significantly, except for MRJP1 and MRJP7, which demonstrated that an enriching effect of MRJP1 and MRJP7 was present during the extraction process. Cyclophosphamide-induced mice were orally administered MRJPs. Results showed that the middle-dose group, which received 0.25 g/(kg·bw) of royal jelly main protein, demonstrated a clear impact on the development of the spleen and liver, the quantity of peripheral blood leukocytes, immunoglobulin content, immune factor level, and the proliferation ability of spleen lymphocytes. A 16S rRNA high-throughput sequencing technology analysis showed that MRJPs could improve the component and richness of intestinal flora and raise the immunity of mice. The above-mentioned results indicated that the application of MRJPs is very likely to have an advantage effect on murine immune functions. [ABSTRACT FROM AUTHOR]

Chitinase, an enzyme that hydrolyzes β-1,4-glycosidic bonds to degrade chitin, is essential for the digestion of chitin in fish. In this study, the chitinase OpCht from Odontobutis potamophila was expressed in Pichia pastoris , and its enzymatic properties and functional effects were evaluated. The findings revealed that OpCht exhibited optimal activity at pH 6.0 and 50 °C, with stability in the pH range of 4–8 and temperatures from 4 to 40 °C. K+, Na+, Ca2+, Mg2+, Mn2+, Hg2+, and Al3+ showed varying degrees of activation on the enzyme. At the end of the 8-week trial, the addition of OpCht significantly increased the height of intestinal villi and the thickness of the muscular layer, leading to significantly weight in the treated groups. The alleviation of intestinal inflammation also resulted in an increased survival rate (SR) of O. potamophila. High concentration treatment groups (2, 4 μg/g) showed significantly elevated digestive enzyme activities, as well as increased antioxidant enzyme activities and immune parameters. These results demonstrate that the P. pastoris expression system has successfully produced the chitinase OpCht from O. potamophila , and the addition of a certain concentration of OpCht can promote fish growth and enhance immune functions, offering a promising enzyme preparation for the aquaculture industry. Eukaryotic expression of chitinase from Odontobutis potamophila and its effects on growth and immunity [Display omitted] • First expression of Odontobutis potamophila chitinase OpCht in Pichia pastoris. • OpCht shows pH and temperature sensitivity, with notably enhanced activity by Mn2+, Hg2+ and Al3+. • Prolonged OpCht supplementation boosts growth, digestive, immune function, and intestinal health in O. potamophila. [ABSTRACT FROM AUTHOR]

Vitamin E is a fat-soluble vitamin that plays a vital function in several biological processes, and fish cannot synthesize it to meet their requirement. So, 56-day research was conducted to examine the influence of vitamin E (vit-E) (α-tocopherol acetate) on the Nile tilapia's growth, digestive enzymes, hematology, histology, and susceptibility to Aeromonas hydrophila. A total of 450 mono-sex Acclimated Nile tilapia (Oreochromis niloticus) were haphazardly dispersed into 30 aquaria, each with a capacity of 100 liters (15 fish/aquarium) to exemplify five groups with six replicates. A control diet (30 % protein) was enriched with 0.0 (E 0), 150 (E 150), 300 (E 300), 600 (E 600), and 1200 (E 1200) mg/kg feed. Fish (13.5 ± 0.12 g) were given the trial diets until obvious satiation thrice daily for 56 days. At the end of the feeding trial, growth performance, digestive enzymes, hematology, and histology for the mid-intestine were examined. Subsequently, twenty fish from each treatment were challenged to contagion with Aeromonas hydrophila bacteria, and fish mortality was recorded for a further 14 days. At the end of the bacterial challenge, histology for the mid-intestine, liver, and spleen tissues was examined. Growth performance, feed utilization, and digestive enzyme secretion (proteases, lipase, and α-amylase) were substantially (P < 0.5) improved with raising vit-E levels in fish feeds up to E1200. Increasing the vit-E doses improved fish gut histomorphology by increasing the count and size of intestinal folds bordered by well-arranged enterocytes. The body composition was not influenced by dietary vitamin E, except lipid content, which increased substantially as vitamin E levels increased. Fish fed with vita-E enriched diets had higher resistance to A. hydrophila infection; however, the control group exhibited the greatest fish mortality rate (80 %), while the lowest rate was observed at E 1200 (30 %). Hepatic and spleen tissues in the control group (E 0) showed severe congestion and degeneration, whereas vit-E-treated fish groups progressively recovered normal histomorphology depending on the vit-E doses. Finally, this research recommends feeding Nile tilapia on vit-E, particularly 1200 mg/kg feed, to enhance its performance, welfare status, and resistance to A. hydrophila contagion. • Vitamin E, α-tocopherol acetate enhanced Nile tilapia's growth rate and feed efficacy. • α-tocopherol acetate improves the digestive enzyme secretions in the Nile tilapia intestine. • An α-tocopherol acetate-enriched diet enhanced the intestinal histological structure of Nile tilapia. • Vitamin E improved the hematological status of Nile tilapia. • α-tocopherol acetate alleviated the adverse impact of bacteria on the fish liver and spleen. [ABSTRACT FROM AUTHOR]

This study was examined to investigate the effect of Azomite (AZO) on the growth performance, immune function, and bone mineralization of broiler chickens. A total of 240-d old male chicks were randomly assigned into four treatments with six replicates (n = 10), which included control (basal diet), basal diet +0.25% AZO, basal diet + 0.50% AZO and basal diet + kitasamycin as antibiotic growth promoter (AGP). The results indicate that live body weight (LBW), average daily gain (ADG) and feed conversion ratio (FCR) were significantly (p <.05) improved in AZO 0.25% and 0.50% than the control. The weight of bursa of Fabricus was significantly (p <.05) higher in AZO-0.25% and AZO-0.50% than control. Total protein (TP), globulin, IgA and IgG levels were significantly (p <.05) increased with AZO supplemented treatments. Tibia diameter tibia breaking strength was significantly (p <.05) increased in AZO- 0.25% and AZO-0.50% treatment. In conclusion, the results indicated that addition of AZO at the doses of 0.25% and 0.50% in the diet had beneficial effects on growth performance, immune functions and tibia breaking strength. [ABSTRACT FROM AUTHOR]

The aging process often leads to immune-related diseases, including infections, tumors, and autoimmune disorders. Recently, researchers identified a special subpopulation of B cells in elderly female mice that increases with age and accumulates prematurely in mouse models of autoimmune diseases or viral infections; these B cells are known as age-related B cells (ABCs). These cells possess distinctive cell surface phenotypes and transcriptional characteristics, and the cell population is widely recognized as CD11c + CD11b + T-bet + CD21 - CD23 - cells. Research has shown that ABCs are a heterogeneous group of B cells that originate independently of the germinal center and are insensitive to B-cell receptor (BCR) and CD40 stimulation, differentiating and proliferating in response to toll-like receptor 7 (TLR7) and IL-21 stimulation. Additionally, they secrete self-antibodies and cytokines to regulate the immune response. These issues have aroused widespread interest among researchers in this field. This review summarizes recent research progress on ABCs, including the functions and regulation of ABCs in aging, viral infection, autoimmune diseases, and organ transplantation., (© 2025 Wiley Periodicals LLC.)

Dietary selenium (Se) is an essential component that supports fish growth and the immune system. This review attempts to provide insight into the biological impacts of dietary Se, including immunological responses, infection defense, and fish species growth, and it also identifies the routes via which it enters the aquatic environment. Dietary Se is important in fish feed due to its additive, antioxidant, and enzyme properties, which aid in various biological processes. However, excessive intake of it may harm aquatic ecosystems and potentially disrupt the food chain. This review explores the diverse natures of dietary Se, their impact on fish species, and the biological methods for eliminating excesses in aquatic environments. Soil has a potential role in the distribution of Se through erosion from agricultural, industrial, and mine sites. The research on dietary Se’s effects on fish immune system and growth can provide knowledge regarding fish health, fish farming strategies, and the health of aquatic ecosystems, promoting the feed industry and sustainable aquaculture. This review provides data and references from various research studies on managing Se levels in aquatic ecosystems, promoting fish conservation, and utilizing Se in farmed fish diets.

The objective of the current study was to quantify the degree of white matter (WM) abnormalities in chronic and virally suppressed HIV-infected (HIV+) persons while carefully taking into account demographic and disease factors. Diffusion tensor imaging (DTI) was conducted in 40 HIV- and 82 HIV+ men with comparable demographics and life style factors. The HIV+ sample was clinically stable with successful viral control. Diffusion was measured across 32 non-colinear directions with a b-value of 1000 s/mm2; fractional anisotropy (FA) and mean diffusivity (MD) maps were quantified with Itrack IDL. Using the ENIGMA DTI protocol, FA and MD values were extracted for each participant and in 11 skeleton regions of interest (SROI) from standard labels in the JHU ICBM-81 atlas covering major striato-frontal and parietal tracks. We found no major differences in FA and MD values across the 11 SROI between study groups. Within the HIV+ sample, we found that a higher CNS penetrating antiretroviral treatment, higher current CD4+ T cell count, and immune recovery from the nadir CD4+ T cell count were associated with increased FA and decreased MD (p

Purpose: To evaluate the clinical efficacy of imatinib mesylate plus radiotherapy for the treatment of acute leukemia and its effect on immune function. Methods: A retrospective study was conducted on 88 patients with acute leukemia admitted to Zhuji Affiliated Hospital of Shaoxing University between July 2017 and July 2021. They were assigned (randomly, 1:1) to a control group (radiotherapy) or a study group (imatinib mesylate plus radiotherapy) according to different treatment regimens. Outcome measures assessed included the clinical efficacy of the treatments in the patients and their immune functions. Results: The two groups did not show any significant differences with regard to general patient profiles. After treatment, both groups presented reduced white blood cell (WBC) and platelet count (PLT) and elevated red blood cells count (RBC). The level of hemoglobin (Hb) level showed a slight decline in the control group but a significant increase in the study group (p < 0.05). The study group showed better improvement in the levels of WBC, PLT, RBC, and Hb than the control group (p < 0.05). The absolute values of peripheral blood mature neutrophils decreased in both groups after treatment, down to the lowest level at week 2, but rebounded, with higher absolute values in the study group at weeks 2, 3, and 4 of treatment (p < 0.05). Imatinib mesylate plus radiotherapy was associated with higher efficacy, compared with radiotherapy alone (p < 0.05). Conclusion: Radiotherapy plus imatinib mesylate effectively enhances the immune functions of acute leukemia patients, mitigates inflammatory responses, alleviates clinical symptoms, and boosts clinical efficacy. Further clinical trials are, however, required prior to general application in clinical practice. [ABSTRACT FROM AUTHOR]

The role of Notch in the immune system was first described in the late 90s. Reports revealed that Notch is one of the most conserved developmental pathways involved in diverse biological processes such as the development, differentiation, survival and functions of many immune populations. Here, we provide an extended view of the pleiotropic effects of the Notch signaling on the innate lymphoid cell (ILC) biology. We review the current knowledge on Notch signaling in the regulation of ILC differentiation, plasticity and functions in diverse tissue types and at both the fetal and adult developmental stages. ILCs are early responder cells that secrete a large panel of cytokines after stimulation. By controlling the abundance of ILCs and the specificity of their release, the Notch pathway is also implicated in the regulation of their functions. The Notch pathway is therefore an important player in both ILC cell fate decision and ILC immune response.

Honeybees cannot synthesize arachidonic acid (ARA) themselves, only obtain it from food. Most pollen is deficient or contains a small amount of ARA. The necessity of supplementary ARA in bees' diet has not been studied. The objective of this study was to investigate the effects of dietary ARA levels on the growth and immunity of Apis mellifera ligustica. A total of 25 honeybee colonies were randomly assigned to five dietary groups which were fed basic diets supplemented with 0, 2, 4, 6, and 8% of ARA. The diet with 4% ARA improved the body weight of newly emerged worker bees compared with the control group. Supplement of ARA in honeybee diets changed the fatty acid composition of honeybee body. SFA and MUFA contents of bees' body declined, and PUFA content rised in the ARA group. Compared with the control group, the supplement of ARA in honeybee diets increased the contents of ARA, C22:6n-3 (DHA) and C18:3n-6 in bees' body significantly, but decreased the contents of C16:1 and C18:3n-3. The diet supplied with 4% ARA reduced the mortality rate of honeybee infected with Escherichia coli. The activity of immune enzymes (phenoloxidase, antitrypsin, and lysozyme) and the mRNA expression levels of immune genes (defensin-2, toll, myd88, and dorsal) were improved by ARA diets to varying degrees depending on the ARA levels, especially 4% ARA. These results suggested that dietary ARA could improve the growth, survival, and immune functions of honeybees. Supplement of ARA in bees' diet would be valuable for the fitness of honeybees. [ABSTRACT FROM AUTHOR]

The ingestion of certain probiotics has been suggested as a promising nutritional strategy to improve aging. The objective of this work was to evaluate the effects of the daily intake, for a month, of a new probiotic Akkermansia muciniphila (AKK) (2 × 108 cfu/100µL PBS) on behavior, as well as function and redox state of immune cells of old female ICR-CD1 mice (OA group). For this, several behavioral tests were performed, and function and oxidative-inflammatory stress parameters of peritoneal leukocytes were analyzed in OA group, in a group of the same age that did not take AKK (old control, OC group) and in another adult control (AC) group. The results showed, in OA group, a significant improvement of several behavioral responses (coordination, balance, neuromuscular vigor, exploratory ability and anxiety like-behaviors), as well as in immune functions (chemotaxis, phagocytosis, NK activity and lymphoproliferation) and in oxidative stress parameters (glutathione peroxidase and reductase activities, oxidized glutathione and lipid oxidation concentrations) of the peritoneal leukocytes in comparison to those observed in OC group. In addition, peritoneal immune cells from the OA group released lower basal concentrations of pro-inflammatory cytokines (IL-2, IL-6 and TNF-α) compared to those from the OC group. The values of parameters in OA were similar to those in AC group. These improvements in the old mice receiving the probiotic were reflected in an increase in their lifespan. In conclusion, our data indicate that AKK supplementation for a short period could be a good nutritional strategy to promote healthy longevity. [ABSTRACT FROM AUTHOR]

Abstract Background Fasciola gigantica infection threatens the health of both humans and animals in the world. The excretory/secretory products (ESPs) of this fluke has been reported to impair the activation and maturation of immune cells. We have previously shown the influence of F. gigantica ESPs (FgESPs) on the maturation of buffalo dendritic cells (DCs). However, the underlying mechanisms remain unclear. The objective of this study was to investigate the potency of FgESPs in shifting the differentiation and immune functions of buffalo DCs. Methods Buffalo DCs were incubated with FgESPs directly or further co-cultured with lymphocytes in vitro. qRT-PCR was employed to determine the gene expression profile of DCs or the mixed cells, and an ELISA was used to measure cytokine levels in the supernatants. Hoechst and Giemsa staining assays, transmission electron microscopy, caspase-3/7 activity test and histone methylation test were performed to determine DC phenotyping, apoptosis and methylation. To investigate the mechanism involved with DNA methylation, a Co-IP assay and immunofluorescent staining assay were performed to observe if there was any direct interaction between FgESPs and DNMT1/TET1 in buffalo DCs, while RNAi technology was employed to knockdown DNMT1 and TET1 in order to evaluate any different influence of FgESPs on DCs when these genes were absent. Results qRT-PCR and ELISA data together demonstrated the upregulation of DC2 and Th2/Treg markers in DCs alone and DCs with a mixed lymphocyte reaction (MLR), suggesting a bias of DC2 that potentially directed Th2 differentiation in vitro. DC apoptosis was also found and evidenced morphologically and biochemically, which might be a source of tolerogenic DCs that led to Treg differentiation. In addition, FgESPs induced methylation level changes of histones H3K4 and H3K9, which correlate with DNA methylation. Co-IP and immunofluorescent subcellular localization assays showed no direct interaction between the FgESPs and DNMT1/TET1 in buffalo DCs. The productions of IL-6 and IL-12 were found separately altered by the knockdown of DNMT1 and TET1 in DCs after FgESPs treatment. Conclusions FgESPs may induce the DC2 phenotype or the apoptosis of buffalo DCs to induce the downstream Th2/Treg response of T cells, possibly through a DNMT1- or TET1-dependent manner(s).

Alzheimer's disease (AD) is the leading type of dementia in aging people and is a progressive condition that causes neurodegeneration, resulting in confusion, memory loss, and deterioration of mental functions. AD happens because of abnormal twisting of the microtubule tau protein in neurons into a tangled neurofibrillary structure. Different factors responsible for AD pathogenesis include heavy metals, aging, cardiovascular disease, and environmental and genetic factors. Market available drugs for AD have several side effects that include hepato‐toxicity, accelerated cognitive decline, worsened neuropsychiatric symptoms, and triggered suicidal ideation. Therefore, an emerging alternative therapeutic approach is probiotics, which can improve AD by modulating the gut‐brain axis. Probiotics modulate different neurochemical pathways by regulating the signalling pathways associated with inflammation, histone deacetylation, and microglial cell activation and maturation. In addition, probiotics‐derived metabolites (i.e., short‐chain fatty acid, neurotransmitters, and antioxidants) have shown ameliorative effects against AD. Probiotics also modulate gut microbiota, with a beneficial impact on neural signalling and cognitive activity, which can attenuate AD progression. Therefore, the current review describes the etiology and mechanism of AD progression as well as various treatment options with a focus on the use of probiotics. Practical applications: In an aging population, dementia concerns are quite prevalent globally. AD is one of the most commonly occurring cognition disorders, which is linked to diminished brain functions. Scientific evidence supports the findings that probiotics and gut microbiota can regulate/modulate brain functions, one of the finest strategies to alleviate such disorders through the gut‐brain axis. Thus, gut microbiota modulation, especially through probiotic supplementation, could become an effective solution to ameliorate AD. [ABSTRACT FROM AUTHOR]

Our objective was to evaluate the effect of colostrum feeding times on genome-wide gene expression of neonatal calves. In total, twenty-seven calves were assigned to three colostrum feeding treatments: within 45 min (TRT0h, n = 9), 6 h (TRT6h, n = 9) and 12 h (TRT12h, n = 9). Ileum tissues were collected at 51 h and transcriptomic analysis was conducted. Uniquely expressed genes were identified in TRT0h group with enriched "Antigen Presentation" function. Meanwhile, the weighted gene co-expression network analysis (WGCNA) identified four significant gene modules (|correlation| > 0.50 and P ≤ 0.05). In particular, Turquoise gene module with the enriched "Cadherin binding involved in cell-cell adhesion" and "Cell-cell adherences junction" GO terms were significantly correlated with Faecalibacterium prausnitzii (R = −0.70, P < 0.01) and Bifidobacterium (R = −0.55, P < 0.01). Our findings suggest feeding colostrum without delay could stimulate the expression of genes involved in immune function development related to host response and microbial colonization in neonatal claves. • This is the first study to explore the effect of colostrum feeding times on the genome-wide gene expression in the ileum of neonatal calves. • Our findings suggested that delaying colostrum feeding to 6 or 12 h after birth postponed immune system development of neonatal claves. • Meanwhile, the relationships between bacterial population and the KEGG pathways "NOD-like receptor (NLRs)", "Toll-like receptor (TLR)" and "RIG-I-like receptors" further suggested that mucosa-attached bacteria play an important role in host immune system and gut barrier development. [ABSTRACT FROM AUTHOR]

Langerhans cells (LCs), residing in the epidermis, are able to induce potent immunogenic responses and also to mediate immune tolerance. We propose that tolerogenic and immunogenic responses of LCs are directed by signaling from the epidermis and involve counter‐acting gene circuits that are coupled to a core maturation gene module. We base our analysis on recent genetic and genomic findings facilitating the understanding of the molecular mechanisms controlling these divergent immune functions. Comparing gene regulatory network (GRN) analyses of various types of dendritic cells (DCs) including LCs we integrate signaling‐dependent (TGFβ, EpCAM, β‐Catenin) and transcription factor (IRF4, IRF1, NFκB) regulated gene circuits that appear to orchestrate the distinctive LC functional states. Our model proposes, that while epidermal signaling in the steady‐state promotes LC tolerogenic function, the disruption of cell‐cell contacts coupled with inflammatory signaling induces LC immunogenic programing. The conceptual framework emphasizes the sensing of discrete epidermal and inflammatory cues by resident LCs in dictating their genomic programing and cell state dynamics. [ABSTRACT FROM AUTHOR]

Rainbow trout (Oncorhynchus mykiss) is one of the most common aquaculture fish species worldwide. Vibriosis disease outbreaks cause significant setbacks to aquaculture. The stress and immune responses are bidirectionally modulated in response to the health challenges. Therefore, an investigation into the regulatory mechanisms of the stress and immune responses in trout is invaluable for identifying potential vibriosis treatments. We investigated the transcriptional profiles of genes associated with stress and trout immune functions after Vibrio anguillarum infection. We compared the control trout (CT, 0.9% saline injection), asymptomatic trout (AT, surviving trout with minor or no symptoms after bacteria injection), and symptomatic trout (ST, moribund trout with severe symptoms after bacteria injection). Our results showed activated immunomodulatory genes in the cytokine network and downregulated glucocorticoid and mineralocorticoid receptors in both AT and ST, indicating activation of the proinflammatory cytokine cascade as a common response in AT and ST. Moreover, the AT specifically activated the complement- and TNF-associated immune defenses in response to V. anguillarum infection. However, the complement and coagulation cascades, as well as steroid hormone homeostasis in ST, were disturbed by V. anguillarum. Our studies provide new insights toward understanding regulatory mechanisms in stress and immune functions in response to diseases.

Rainbow trout (Oncorhynchus mykiss) is one of the most common aquaculture fish species worldwide. Vibriosis disease outbreaks cause significant setbacks to aquaculture. The stress and immune responses are bidirectionally modulated in response to the health challenges. Therefore, an investigation into the regulatory mechanisms of the stress and immune responses in trout is invaluable for identifying potential vibriosis treatments. We investigated the transcriptional profiles of genes associated with stress and trout immune functions after Vibrio anguillarum infection. We compared the control trout (CT, 0.9% saline injection), asymptomatic trout (AT, surviving trout with minor or no symptoms after bacteria injection), and symptomatic trout (ST, moribund trout with severe symptoms after bacteria injection). Our results showed activated immunomodulatory genes in the cytokine network and downregulated glucocorticoid and mineralocorticoid receptors in both AT and ST, indicating activation of the proinflammatory cytokine cascade as a common response in AT and ST. Moreover, the AT specifically activated the complement- and TNF-associated immune defenses in response to V. anguillarum infection. However, the complement and coagulation cascades, as well as steroid hormone homeostasis in ST, were disturbed by V. anguillarum. Our studies provide new insights toward understanding regulatory mechanisms in stress and immune functions in response to diseases. [ABSTRACT FROM AUTHOR]

Recent scientific evidence has indicated that the elderly have increased risk of COVID-19 infections, with over 70s and 80s being hardest hit – especially residents of care homes and in clinical settings, ethnic minorities, people who work indoors and those who are overweight and obese. Other potential risk factors include lack of exposure to sunlight, darker skin pigmentation, co-morbidities, poor diet, certain medications, disadvantaged social and economic status, and lifestyle factors such as smoking and excessive consumption of alcohol. A key question is to understand how and why certain groups of people are more susceptible to COVID-19, whether they have weakened immune systems and what the roles of good nutrition and specific micronutrients are in supporting immune functions. A varied and balanced diet with an abundance of fruits and vegetables and the essential nutrients like vitamin D, vitamin A, B vitamins (folate, vitamin B6 and vitamin B12), vitamin C and the minerals, Fe, Cu, Se and Zn are all known to contribute to the normal functions of the immune system. Avoidance of deficiencies and identification of suboptimal intakes of these micronutrients in targeted groups of patients and in distinct and highly sensitive populations could help to strengthen the resilience of people to the COVID-19 pandemic. It is important to highlight evidence-based public health messages, to prevent false and misleading claims about the benefits of foods and food supplements and to communicate clearly that the extent of knowledge between micronutrients and COVID-19 infection is still being explored and that no diet will prevent or cure COVID-19 infection. Frequent handwashing and social distancing will be critical to reduce transmission. [ABSTRACT FROM AUTHOR]

OBJECTIVE: In response to the COVID-19 disaster, people have developed several psychological problems mainly stress, anxiety, and depression. These psychological problems have been seen in either normal people during the lockdown (who are waiting to get infected with COVID-19) and patients with COVID-19 (who are waiting for death). These psychological problems adversely affect immune functions causing more increase in the severity of COVID-19 associated disorders and death rates. Increasing the aerobic capacity is one of the effective methods that could be used to decrease stress, anxiety, and depression. Besides, increasing the aerobic capacity increases immune functions through autonomic regulation. Thus, this review was developed to summarize the effect of increasing the aerobic capacity on psycho-immune hormones commonly disturbed in people during the lockdown or patients with COVID-19 infection. MATERIALS AND METHODS: This review was carried out by searching through Web of Science, Scopus, EBSCO, Medline databases. The search was conducted over clinical trials, literature reviews, and systematic reviews. The search included the possible effects of increasing the aerobic capacity on the functions of psycho-immune hormones. RESULTS: This review found that increasing the aerobic capacity can decrease psychological problems commonly seen in people with COVID-19 and increase immune functions by modulating the levels of glucocorticoid, oxytocin, insulin, thyroid hormones. CONCLUSIONS: This review demonstrated that increasing the aerobic capacity is a recommended treatment for decreasing the psychological problems commonly seen in people with COVID-19 because it has the potential for decreasing psychological problems and improving immune functions which would help counter COVID-19. [ABSTRACT FROM AUTHOR]

[Objectives] To explore the effects of Guizhi Shaoyao Zhimu Decoction on laboratory indicators and immune functions of patients with rheumatoid arthritis. [Methods] A total of 110 patients with rheumatoid arthritis admitted to the Second Department of Orthopedics, the Affiliated Chinese and Western Medicine Hospital of Nanjing, Nanjing University of Chinese Medicine from December 2014 to December 2016 were selected as the research objects and divided into a control group and an observation group using the random number table method, with 55 cases in each group. The control group was treated with conventional western medicine, and the observation group was treated with Guizhi Shaoyao Zhimu Decoction on the basis of the control group. Both groups were treated for one month. The clinical effects, improvement of clinical symptoms, laboratory indicators and immune function indicator levels between the two groups were compared; the incidence of adverse reactions in the two groups was counted. [Results] The total effective rate of the observation group was 92.73%, higher than that of the control group (78.18%) (P<0.05). Compared with that before treatment, after one month of treatment, the grip strength of the two groups increased, and the observation group was greater than the control group (P <0.05) ; the morning stiffness time and 20 m walking time of both groups were shortened, and the observation group was shorter than the control group (P <0.05) ; the number of joint tenderness, joint swelling, ESR, MPV, PDW, serum CRP, plasma IgA, IgG, IgM, RF levels in both groups decreased, and the observation group was lower than the control group (P <0.05) ; the serum C3 levels in both groups increased, and the observation group was higher than the control group (P < 0.05). During the treatment, the incidence of adverse reactions in the observation group was 0.00%, which was lower than that in the control group (10.91%, P <0. 05) [Conclusions] Using Guizhi Shaoyao Zhimu Decoction to treat rheumatoid arthritis can improve the laboratory indicators of patients, and enhance their immune functions, improve the curative effect, and the safety is high. [ABSTRACT FROM AUTHOR]

Oligodendrocyte precursor cells (OPCs) have long been regarded as progenitors of oligodendrocytes, yet recent advances have illuminated their multifaceted nature including their emerging immune functions. This review seeks to shed light on the immune functions exhibited by OPCs, spanning from phagocytosis to immune modulation and direct engagement with immune cells across various pathological scenarios. Comprehensive understanding of the immune functions of OPCs alongside their other roles will pave the way for targeted therapies in neurological disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Haroon, Seerapu, Fang, Weß and Bai.)

One of the major challenges the scientific community faces today is the lack of translational data generated from mouse trials for human health application. Housing temperature-dependent chronic cold stress in laboratory rodents is one of the key factors contributing to lack of translatability because it reveals major metabolic differences between humans and rodents. While humans tend to operate at temperatures within their thermoneutral zone, most laboratory rodents are housed at temperatures below this zone and have an increased energy demand to generate heat. This has an impact on the immune system of mice and thus affects results obtained using murine models of human diseases. A limited number of studies and reviews have shown that results obtained on mice housed at thermoneutrality were different from those obtained from mice housed in traditional housing conditions. Most of those studies, focused on obesity and cancer, found that housing mice at thermoneutrality changed the outcomes of the diseases negatively and positively, respectively. In this review, we describe how thermoneutrality impacts the immune system of rodents generally and in the context of different disease models. We show that thermoneutrality exacerbates cardiovascular and auto-immune diseases; alleviates asthma and Alzheimer’s disease; and, changes gut microbiome populations. We also show that thermoneutrality can have exacerbating or alleviating effects on the outcome of infectious diseases. Thus, we join the call of others in this field to urge researchers to refine murine models of disease and increase their translational capacity by considering housing at thermoneutrality for trials involving rodents.

The present study examined the effects of dietary vitamin A (VA) on antioxidant functions, immune functions and production performance in farmed sika deer. Forty healthy male sika deer (initial body weight (BW): 47.07 ± 4.75 kg; 8 months of age) were randomly assigned to four treatments on the basis of BW. The dietary treatments included a basal diet (containing 330 U/kg VA) supplemented with 0 (control), 2500, 5000 or 10,000 U/kg retinol acetate (500,000 U/g, Rovimix A500, Roche, Basel, Switzerland). The results showed that deer fed a diet supplemented with 5000 U/kg VA had higher (p

Platelets serotonin (5-hydroxytrytamine, 5-HT) uptake and storage in dense granules is tightly regulated by the serotonergic transport system in the blood. Several 5-HT transporters (5-HTTs) have been identified in the vasculature and blood cells, beyond them 5-HTT is the major 5-HT transporter in platelets. Abnormal 5-HT concentrations in the blood plasma or increased platelet 5-HT uptake or abnormal release contribute to the development of various diseases in the vasculature. Consequently, several clinical trials suggested the positive therapeutic effects of 5-HTT blockade in the circulation. Inhibition of 5-HT strongly attenuates autocrine and paracrine functions of platelets, influencing platelet aggregation, vascular contraction, permeability, tissue repair, wound healing, immunity and cancer. Here, we highlight the current state of basic biological research regarding the hemostatic and non-hemostatic functions of platelet-derived 5-HT in normal and disease conditions. We also describe the physiological consequences of targeting platelet 5-HT functions in thrombosis, stroke, inflammation and cancer to overcome common health problems.

One of the major challenges the scientific community faces today is the lack of translational data generated from mouse trials for human health application. Housing temperature-dependent chronic cold stress in laboratory rodents is one of the key factors contributing to lack of translatability because it reveals major metabolic differences between humans and rodents. While humans tend to operate at temperatures within their thermoneutral zone, most laboratory rodents are housed at temperatures below this zone and have an increased energy demand to generate heat. This has an impact on the immune system of mice and thus affects results obtained using murine models of human diseases. A limited number of studies and reviews have shown that results obtained on mice housed at thermoneutrality were different from those obtained from mice housed in traditional housing conditions. Most of those studies, focused on obesity and cancer, found that housing mice at thermoneutrality changed the outcomes of the diseases negatively and positively, respectively. In this review, we describe how thermoneutrality impacts the immune system of rodents generally and in the context of different disease models. We show that thermoneutrality exacerbates cardiovascular and auto-immune diseases; alleviates asthma and Alzheimer's disease; and, changes gut microbiome populations. We also show that thermoneutrality can have exacerbating or alleviating effects on the outcome of infectious diseases. Thus, we join the call of others in this field to urge researchers to refine murine models of disease and increase their translational capacity by considering housing at thermoneutrality for trials involving rodents. [ABSTRACT FROM AUTHOR]

Child malnutrition is a global public health challenge. A protein malnutrition (PM) model in young mice was established in this study. The efficacy of an ocean-based protein (APP) extracted from by-catch fish as compared to casein and soy on restoring body weight, bone growth, and immunity of PM mice was evaluated. Results show that supplementation of APP increases body weight, lean muscle mass, bone area, mineral content and density. APP supplementation increases spleen, thymus weight, and interlukin-6 production. In conclusion, APP is an alternative source of protein to effectively restore body weight, bone growth and immune function of PM mice. [ABSTRACT FROM AUTHOR]

• L-TNFR10-like protein is specifically expressed on lamprey granulocytes and can be used as a potential granulocyte marker molecule. • L-TNFR10-like plays crucial immune roles in lampreys. • Overexpression of L-tnfr10 -like gene can reduce cell viability and activate NF-κB transcription factor. Tumor necrosis factor receptor superfamily (TNFRSF) is an ancient protein superfamily. By binding to tumor necrosis factor (TNF), it can participate in inflammatory response, apoptosis, lymphocyte homeostasis and tissue development. Seven TNFR members have previously been identified in lampreys but detailed functions of TNFR members are not yet to be resolved. Here, we demonstrate some of the distinguishing features of TNFR10-like member which belongs to TNFRSF. The immunohistochemical results indicate that the TNFR10-like protein is abundant in vascular epithelial cells of the lamprey typhlosole and gills. The expression of tnfr10 -like gene has a significantly increased at transcription level after Vibrio anguillarum , Staphylococcus aureus and Poly (I:C) stimulation. Notably, TNFR10-like is specifically expressed in the granulocytes of lamprey peripheral blood and supraneural body. Besides, overexpression tnfr10 -like gene in HEK-293 T cells cause a decrease in cell activity and able to activate nuclear transcription factor-κB (NF-κB). Together, these results imply that L-TNFR10-like may play a vital role as a potential marker in lamprey granulocytes and may also be involved in regulation of immune response mediated by itself. [ABSTRACT FROM AUTHOR]

Background: Fasciola gigantica infection threatens the health of both humans and animals in the world. The excretory/secretory products (ESPs) of this fluke has been reported to impair the activation and maturation of immune cells. We have previously shown the influence of F. gigantica ESPs (FgESPs) on the maturation of buffalo dendritic cells (DCs). However, the underlying mechanisms remain unclear. The objective of this study was to investigate the potency of FgESPs in shifting the differentiation and immune functions of buffalo DCs. Methods: Buffalo DCs were incubated with FgESPs directly or further co-cultured with lymphocytes in vitro. qRT-PCR was employed to determine the gene expression profile of DCs or the mixed cells, and an ELISA was used to measure cytokine levels in the supernatants. Hoechst and Giemsa staining assays, transmission electron microscopy, caspase-3/7 activity test and histone methylation test were performed to determine DC phenotyping, apoptosis and methylation. To investigate the mechanism involved with DNA methylation, a Co-IP assay and immunofluorescent staining assay were performed to observe if there was any direct interaction between FgESPs and DNMT1/TET1 in buffalo DCs, while RNAi technology was employed to knockdown DNMT1 and TET1 in order to evaluate any different influence of FgESPs on DCs when these genes were absent. Results: qRT-PCR and ELISA data together demonstrated the upregulation of DC2 and Th2/Treg markers in DCs alone and DCs with a mixed lymphocyte reaction (MLR), suggesting a bias of DC2 that potentially directed Th2 differentiation in vitro. DC apoptosis was also found and evidenced morphologically and biochemically, which might be a source of tolerogenic DCs that led to Treg differentiation. In addition, FgESPs induced methylation level changes of histones H3K4 and H3K9, which correlate with DNA methylation. Co-IP and immunofluorescent subcellular localization assays showed no direct interaction between the FgESPs and DNMT1/TET1 in buffalo DCs. The productions of IL-6 and IL-12 were found separately altered by the knockdown of DNMT1 and TET1 in DCs after FgESPs treatment. Conclusions: FgESPs may induce the DC2 phenotype or the apoptosis of buffalo DCs to induce the downstream Th2/Treg response of T cells, possibly through a DNMT1- or TET1-dependent manner(s). [ABSTRACT FROM AUTHOR]

Abstract Background The idea that changes to the host immune system are critical for cancer progression was proposed a century ago and recently regained experimental support. Results Herein, the hypothesis that hepatocellular carcinoma (HCC) leaves a molecular signature in the host peripheral immune system was tested by profiling DNA methylation in peripheral blood mononuclear cells (PBMC) and T cells from a discovery cohort (n = 69) of healthy controls, chronic hepatitis, and HCC using Illumina 450K platform and was validated in two validation sets (n = 80 and n = 48) using pyrosequencing. Conclusions The study reveals a broad signature of hepatocellular carcinoma in PBMC and T cells DNA methylation which discriminates early HCC stage from chronic hepatitis B and C and healthy controls, intensifies with progression of HCC, and is highly enriched in immune function-related genes such as PD-1, a current cancer immunotherapy target. These data also support the feasibility of using these profiles for early detection of HCC.

Objective To assess the effects of proteinate complex zinc (PC-Zn) on growth performance, antioxidative function, trace element concentrations and immune function in weaned piglets. Methods Three hundred newly weaned barrows (Duroc×Landrace×Yorkshire), 28 days of age, were randomly allotted to 3 dietary groups of 5 replicate pens per group for 4 weeks of feeding. Experimental diets were: i) zinc deficient diet (ZnD, 24 mg/kg Zn supplementation from ZnSO4), ii) inorganic Zn diet supplemented with 120 mg/kg of Zn from Zn sulfate (ZnSO4), and iii) organic Zn diet supplemented with 120 mg/kg of Zn from PC-Zn. The body weight of pigs were recorded at the beginning, at the middle and at the end of the experiment, and the amount of feed supplied each day was recorded. Five barrows from each dietary treatment group were selected to be anesthetized and euthanized at the end of the trial to determine the Zn, Cu, Fe, and Mn concentrations, the hepatic metallothionein content, the levels of methane dicarboxylic aldehyde (MDA), Mn, and Cu/Zn superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in the spleen, the levels of interleukin (IL)-2, IL-4, IL-10, interferon (IFN)-γ, CD3+, CD4+, and CD8+ T lymphocyte. Results The accumulation of Zn in the spleen, levels of SOD, GSH-Px, IL-4, IL-10, the proportions of CD3+ and CD4+ T lymphocyte, and the ratio of CD4+/CD8+ T lymphocyte were increased by organic Zn supplementation compared to ZnD, while the levels of MDA, IFN-γ, and proportion of CD8+ T lymphocyte were lowered. Conclusion These findings indicate that Zn can improve the antioxidant potential and immune functions of weaned piglets.

Human papillomavirus (HPV) is an etiologic factor in head and neck squamous cell carcinoma (HNSCC). HPV(+) cancers respond favorably to therapy potentially due to more robust anti-tumor immune responses. We hypothesized that tumor-derived exosomes (TEX) produced by HPV(+) or HPV(-) HNSCCs differentially modulate anti-tumor immune responses. Proteomes of exosomes from HPV(+) and HPV(-) HNSCC cell lines were compared in search for proteins putatively involved in the communication with immune system. TEX were isolated from supernatants of HPV(+) (SCC-2, SCC-47, and SCC-90) or HPV(-) (PCI-13 and PCI-30) cells by size exclusion chromatography. A comparison of proteome profiles was performed by high-resolution mass spectrometry. The presence and biological activity of selected immunoregulatory proteins were validated by flow cytometry and co-incubation assays. Exosomes produced by SCC-90 and PCI-30 cells contained 711 proteins, including 80 proteins specific for HPV(+) exosomes and 77 specific for HPV(-) exosomes, associated with similar GO terms such as regulation of cell growth, metabolism, communication, and cellular signaling. Search for proteins localized in the membrane and involved in immune regulation identified a few proteins detected specifically in HPV(+) or HPV(-) exosomes. Only HPV(+) exosomes were enriched in immune effector cell-related CD47 and CD276 antigens; only HPV(-) exosomes contained tumor-protective/growth-promoting antigens, MUC-1 and HLA-DA. Flow cytometry and Western blots confirmed the reciprocal presence/paucity of these proteins in a whole panel of tumor cells and corresponding exosomes. The differential content of protein cargos in HPV(+) and HPV(-) exosomes might contribute to the disparity in immune responses that characterize HPV(+) and HPV(-) HNSCC.