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Islet transplantation is a treatment modality for diabetes mellitus that can maintain insulin levels within a physiologically appropriate range. However, wider clinical application is limited by insufficient donor numbers and a need for lifelong immunosuppression. Despite various clinical and preclinical trials, there is no single standard immunosuppressive regimen that can suppress acute and chronic immune reactions with lower toxicity to grafted islets. One of the strategies for overcoming lifelong immunosuppression is the incorporation of encapsulation technology, which can provide a physical immune barrier by keeping out high molecular weight immune system components, while still allowing low molecular weight oxygen, insulin and nutrients to pass through. Encapsulated islet transplantation approaches that have been studied so far include macroencapsulation, microencapsulation, conformal coating and nanoencapsulation. Herein we will review the basic concepts of islet encapsulation technique, earlier works to recent progress related to clinical studies and corporate investigations on encapsulated islet transplantation.

Although prone to a higher degree of ischemia reperfusion injury (IRI), the use of extended criteria donor (ECD) organs has become reality in transplantation. We therefore postulated that peri-operative perfusion of renal transplants with anti-human T-lymphocyte globulin (ATLG) ameliorates IRI and results in improved graft function. We performed a randomized, single-blinded, placebo-controlled trial involving 50 kidneys (KTx). Prior to implantation organs were perfused and incubated with ATLG (AP) ( = 24 kidney). Control organs (CP) were perfused with saline only ( = 26 kidney). Primary endpoint was defined as graft function reflected by serum creatinine at day 7 post transplantation (post-tx). AP-KTx recipients illustrated significantly better graft function at day 7 post-tx as reflected by lower creatinine levels, whereas no treatment effect was observed after 12 months surveillance. During the early hospitalization phase, 16 of the 26 CP-KTx patients required dialysis during the first 7 days post-tx, whereas only 10 of the 24 AP-KTx patients underwent dialysis. No treatment-specific differences were detected for various lymphocytes subsets in the peripheral blood of patients. Additionally, mRNA analysis of 0-h biopsies post incubation with ATLG revealed no changes of intragraft inflammatory expression patterns between AP and CP organs. We here present the first clinical study on peri-operative organ perfusion with ATLG illustrating improved graft function in the early period post kidney transplantation. www.ClinicalTrials.gov, NCT03377283.

•No vaccine against human VL, though few vaccines licensed for canine VL.•Vaccine alongwith an efficient adjuvant required for long-term protection against VL.•This article is an overview of adjuvants tried with candidate vaccines against VL.•BCG, MPL-SE, GLA-SE and saponin have been extensively assessed against human VL.•Emphasis has been made to explore adjuvants successful in other human diseases. Although there has been an extensive research on vaccine development over the last decade and some vaccines have been commercialized for canine visceral leishmaniasis (CVL), but as yet no effective vaccine is available for anthroponotic VL which may partly be due to the absence of an appropriate adjuvant system. Vaccines alone yield poor immunity hence requiring an adjuvant which can boost the immunosuppressed state of VL infected individuals by eliciting adaptive immune responses to achieve required immunological enhancement. Recent studies have documented the continuous efforts that are being made in the field of adjuvants research in an attempt to render vaccines more effective. This review article focuses on adjuvants, particularly particulate and non-particulate ones, which have been assessed with VL vaccine candidates in several preclinical and clinical trials outlining the induction of immune responses obtained from these studies. Moreover, we have emphasized the applicability of multiple adjuvants combination for an improvement in the potential of a VL vaccine.

The present Porcine circovirus type 2 virus (PCV2) vaccine adjuvants suffer from numerous limitations, such as adverse effects, deficient cell-mediated immune responses, and inadequate antibody production. In this study, we explored the potential of a novel nanoparticle (CS-Au NPs) based on gold nanoparticles (Au NPs) and chitosan (CS) that modified Viola philippica polysaccharide (VPP) as efficient adjuvants for PCV2 vaccine. The characterization demonstrated that CS-Au-VPP NPs had a mean particle size of 507.42 nm and a zeta potential value of −21.93 mV. CS-Au-VPP NPs also exhibited good dispersion and a stable structure, which did not alter the polysaccharide properties. Additionally, the CS-Au-VPP NPs showed easy absorption and utilization by the organism. To investigate their immune-enhancing potential, mice were immunized with a mixture of CS-Au-VPP NPs and PCV2 vaccine. The evaluation of relevant immunological indicators, including specific IgG antibodies and their subclasses, cytokines, and T cell subpopulations, confirmed their immune-boosting effects. The in vivo experiments revealed that the medium-dose CS-Au-VPP NPs significantly elevated the levels of specific IgG antibodies and their subclasses, cytokines, and T cell subpopulations in PCV2-immunized mice. These findings suggest that CS-Au-VPP NPs can serve as a promising vaccine adjuvant due to their stable structure and immunoenhancement capabilities.

Derived from tryptophan, melatonin (MT; N‐acetyl‐5‐methoxytryptamine) is a ubiquitous indoleamine that is widely distributed in species ranging from microorganisms to mammals. It has been associated to play vital roles in the human body like cardiac rhythms, immunological enhancement, and antioxidant activity. In plants, it is a pleiotropic molecule with multiple roles, as it not only performs extensive functions like delaying senescence, growth and development regulation, exerting antioxidant effects, and facilitating adaption of plants to certain biotic and abiotic stress responses but also provides resistance to chilling injury and disease development. This paper reviews the latest progress in the multiple roles of MT in fruits, summarizes the pathways for its biosynthesis, and presents the relation of MT with plant hormones, like auxin, cytokinin, ethylene, gibberellins, abscisic acid, jasmonic, and salicylic acid, and highlights the effect of postharvest application of MT on physiology and quality of fruits, action mechanisms, and safety regulations of MT. Recent trends focus on using alternatives that are safe for postharvest produce and do not have major side effects. MT is a better alternative to hazardous chemicals being commercially used in the postharvest management of fruits and providing future directions for its utilization.

Low persistence, metabolic dysfunction in microenvironment, and tumor‐derived immunosuppression of Natural killer (NK) cells in patients are greatly limited the successful clinical application of NK cell‐based cancer immunotherapy. Interestingly, herein that human serum albumin‐encapsulated black phosphorus quantum dots (BPQDs@HSA) can effectively augment antitumor efficacy of clinical patients‐derived NK cell immunotherapy is found. As the donor of phosphate group, BPQDs@HSA binds with the protein of phosphatidylinositol 4‐phosphate 5‐kinase type‐1 gamma (PIP5K1A) and activates the downstream PI3K‐Akt and mTOR signaling pathways to reprogram cell metabolism of glycolysis and further promote the oxidative phosphorylation, sequentially maintains the cell viability and immunity of NK cells. And multiomics analysis is therefore conducted to reveal the underlying immunoregulation mechanisms, and that BPQDs@HSA can interact with the Toll‐like receptor (TLR) on the NK cell surface and increase the expression level of mTOR, and thus activate downstream NF‐κB signalling pathways to regulate cytokine secretion and enhance immune tumoricidal is found. BPQDs@HSA can also enhance immune surveillance, relieve immune suppression, and inhibit tumor immune escape. Collectively, this study not only demonstrates a successful strategy for nanomedicine‐potentiated immune‐cancer therapy, but also sheds light on the understanding of interface between nanomedicine and immune cells activation. Herein a successful strategy for cancer treatment by nanomedicine‐potentiated NK cell immunotherapy is presented. BPQDs@HSA activates PI3K‐Akt‐mTOR signaling pathways to reprogram cell metabolism of glycolysis and further promote the oxidative phosphorylation, sequentially maintains the cell viability and immunity of NK cells. BPQDs@HSA can also enhance immune tumoricidal and immune surveillance, relieve immune suppression, and inhibit tumor immune escape.

This study evaluated the effects of combining herbal bioactive compounds with organic minerals (Fe and Se) on egg quality, intestinal morphology, and production performance of laying hens. Six dietary treatments (T1–T6), each replicated six times, were arranged in a completely randomized design. Data were analyzed using one-way ANOVA, followed by orthogonal contrast and Bonferroni post hoc tests. The results showed significant effects of treatments on body weight (F = 19.400; p < 0.001), egg mass (F = 3.320; p = 0.020), feed intake (F = 4.205; p = 0.007), and feed conversion ratio (F = 4.141; p = 0.007), while egg weight differences were not significant (p = 0.927). The combination of herbal bioactives with organic Fe and Se minerals enhanced feed efficiency, nutrient absorption, and metabolic performance, as indicated by improved body weight gain and egg mass. Chemically, supplemented hens produced eggs with higher protein levels (albumen 12.03%, yolk 17.40%) and stable organic matter content (∼99%), while maintaining normal yolk cholesterol (702.8 mg/100 g). Mineral biofortification was evident through increased yolk Fe (1.82 mg/100 g) and Se (22.08 µg/100 g) concentrations, accompanied by elevated IgY antibody levels (3163 µg/g), suggesting immunological enhancement. Morphometric observations showed stable liver, gizzard, and heart proportions (CV <10%), indicating consistent metabolic health, while intestinal length uniformity reflected efficient nutrient absorption. Treatment T6 demonstrated the best overall production score (2095.33 ± 47.42), significantly higher than the control (T1 = 1820.67 ± 89.52) and several other treatments (p < 0.05), while T5 exhibited comparable performance (p = 0.343). In conclusion, supplementation with herbal bioactive compounds combined with organic Fe and Se minerals significantly improved egg chemical stability, nutrient composition, feed utilization, and production efficiency. This synergistic formulation represents a sustainable, antibiotic-free strategy for enhancing egg quality and supporting functional, nutrient-enriched egg production in laying hens.

We previously observed the beneficial role of folic acid supplemented from maternal or offspring diet on lamb growth performance and immunity. Twenty-four Hu lambs from four groups (mother received folic acid or not, offspring received folic acid or not) were used in the current study, which was conducted consecutively to elucidate the molecular regulatory mechanisms of folic acid in lambs by analyzing blood metabolome, liver transcriptome, and muscle transcriptome. Serum metabolomics analysis showed that L-homocitrulline, hyodeoxycholic acid, 9-Hpode, palmitaldehyde, N-oleoyl glycine, hexadecanedioic acid, xylose, 1,7-dimethylxanthine, nicotinamide, acetyl-N-formyl-5-methoxykynurenamine, N6-succinyl adenosine, 11-cis-retinol, 18-hydroxycorticosterone, and 2-acetylfuran were down-regulated and methylisobutyrate was up-regulated by the feeding of folic acid from maternal and/or offspring diets. Meanwhile, folic acid increased the abundances of S100A12 and IRF6 but decreased TMEM25 in the liver. In the muscle, RBBP9, CALCR, PPP1R3D, UCP3, FBXL4, CMBL , and MTFR2 were up-regulated, CYP26B1 and MYH9 were down-regulated by the feeding of folic acid. The pathways of bile secretion, biosynthesis of unsaturated fatty acids, linoleic acid metabolism, and herpes simplex virus 1 infection were changed by folic acid in blood, liver, or muscle. Further integrated analysis revealed potential interactions among the liver, blood, and muscle, and the circulating metabolites, hub gene, and pathways, which might be the predominant acting targets of folic acid in animals. These findings provide fundamental information on the beneficial function of folic acid no matter from maternal or offspring, in regulating animal lipid metabolism and immune enhancement, providing a theoretical basis for the use of folic acid from the view of animal health care.

Background Elderly individuals face heightened susceptibility to infectious diseases and diminished vaccine responses. Vaccine adjuvants offer a solution. Despite aluminum adjuvant’s long history, its limitations in inducing strong cellular immunity and protecting immunocompromised individuals restrict its application. Building upon our previous development of zinc salt particle-based risedronate (Zn-RS), we systematically investigated the immunoenhancing effects of Zn-RS in aged mice and thoroughly explored the underlying mechanisms responsible for these observations in this study. Results Compared to formulations using aluminum adjuvant, Zn-RS combined with either varicella-zoster virus glycoprotein E (gE) or SARS-CoV-2 monovalent STFK protein (STFK) elicited significantly higher IgG and neutralization titers, as well as superior long-term humoral immunity. Moreover, Zn-RS induced greater quantities of dendritic cells (DCs), antigen-presenting cells (APCs), follicular helper T (T FH ) cells, Th1/Th2/Th9/Th17 type immune cells, germinal center B cells (GCBs) and plasma cells. Conclusions These findings support Zn-RS as a promising adjuvant candidate for elderly populations, warranting further exploration of its mechanisms and potential applications.

This study aimed to explore the efficacy of zunyimycin C in the immunological enhancement of hypoimmune mice and improvement of cognitive impairment in a mice model of Alzheimer’s disease (AD). Zunyimycin C was administered intranasally to interfere with AD mouse models or gavage to hypoimmune animals. Results of the Morris water maze (MWM) showed that zunyimycin may improve the learning and memory abilities of the AD mice model. The results of differential expression analysis of mRNA levels of inflammatory factors and pathways in brain tissues of the AD mouse model suggested that differential expression was more obvious under Zun-Int L. Western blot revealed that the relative expression of glial fibrillary acidic protein in the brain tissue of the AD mouse model in the Zun-Pre group was significantly higher than that in the other groups, and the difference was statistically significant. The relative expression of interleukin (IL)-6 protein in the brain tissue of mice in the low-dose intervention group was significantly lower than that in the other groups, and the difference was statistically significant. As for hypoimmune animals, short chain fatty acids (SCFAs) assay and intestinal flora assay results showed that zunyimycin C may change intestinal flora diversity and SCFA biosynthesis. The prophylactic administration of zunyimycin C could not inhibit acute neuroinflammation in AD mice. Zunyimycin C may participate in the immune response by activating the Ras-Raf-MEK-ERK signaling pathway to stimulate microglia to produce more inflammatory factors. Zunyimycin C may inhibit autophagy by activating the PI3K-AKT-mTOR signaling pathway, promote cell survival, mediate neuroprotective effects of reactive microglia and reactive astrocytes, and reduce IL-1β in brain tissue and IL-6 secretion, thereby attenuating neuroinflammation in AD mice and achieving the effect of improving learning and memory impairment. Zunyimycin C may play a role in immunological enhancement by changing intestinal flora diversity and SCFAs.