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Aeromonas veronii is an opportunistic pathogen that poses great threat to aquaculture and human health, so there is an urgent need for green and efficient methods to deal with its infection. In this study, single and double gene deletion strains (AV-ΔaroA, AV-Δppk1 and AV-ΔaroA/ppk1) that can be stably inherited were constructed. Pathogenicity test showed that the toxicity of AV-ΔaroA and AV-ΔaroA/ppk1 was significantly lower compared to wild-type A. veronii. Biological characterization analysis revealed that the decrease in pathogenicity might be due to the declined growth, motility, biofilm formation abilities and the expression of virulence-related genes in mutants. Subsequently, we evaluated the efficacy of AV-ΔaroA/ppk1 as a live attenuated vaccine (LAV). Safety assessment experiments showed that AV-ΔaroA/ppk1 injected at a concentration of 3 × 107 CFU/mL was safe for C. carassius. The relative percentage survival of AV-ΔaroA/ppk1 was 67.85 %, significantly higher than that of the inactivated A. veronii, which had an RPS of 54.84 %. This improved protective effect was mainly attributed to the increased levels of A. veronii specific IgM antibody, enhanced alkaline phosphatase, lysozyme and superoxide dismutase activities, as well as higher expression levels of several immune related genes. Together, these findings deepen our understanding of the functional roles of aroA and ppk1 in A. veronii pathogenicity, provide a good candidate of LAV for A. veronii.

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Sarcoidosis is a multiorgan granulomatous disease that lacks diagnostic biomarkers and targeted treatments. Using blood and skin from patients with sarcoid and non-sarcoid skin granulomas, we discovered that skin granulomas from different diseases exhibit unique immune cell recruitment and molecular signatures. Sarcoid skin granulomas were specifically enriched for type 1 innate lymphoid cells (ILC1s) and B cells and exhibited molecular programs associated with formation of mature tertiary lymphoid structures (TLSs), including increased CXCL12/CXCR4 signaling. Lung sarcoidosis granulomas also displayed similar immune cell recruitment. Thus, granuloma formation was not a generic molecular response. In addition to tissue-specific effects, patients with sarcoidosis exhibited an 8-fold increase in circulating ILC1s, which correlated with treatment status. Multiple immune cell types induced CXCL12/CXCR4 signaling in sarcoidosis, including Th1 T cells, macrophages, and ILCs. Mechanistically, CXCR4 inhibition reduced sarcoidosis-activated immune cell migration, and targeting CXCR4 or total ILCs attenuated granuloma formation in a noninfectious mouse model. Taken together, our results show that ILC1s are a tissue and circulating biomarker that distinguishes sarcoidosis from other skin granulomatous diseases. Repurposing existing CXCR4 inhibitors may offer a new targeted treatment for this devastating disease.

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The CLARINET trial led to the approval of lanreotide for the treatment of patients with gastroenteropancreatic neuroendocrine tumors (NETs). It is hypothesized that lanreotide regulates proliferation, hormone synthesis, and other cellular functions via binding to somatostatin receptors (SSTR1-5) present in NETs. However, our knowledge of how lanreotide affects the immune system is limited. In vitro studies have investigated functional immune response parameters with lanreotide treatment in healthy donor T cell subsets, encompassing the breadth of SSTR expression, apoptosis induction, cytokine production, and activity of transcription factor signaling pathways. In our study, we characterized in vitro immune mechanisms in healthy donor T cells in response to lanreotide. We also studied the in vivo effects by looking at differential gene expression pre- and post-lanreotide therapy in patients with NET. Immune-focused gene and protein expression profiling was performed on peripheral blood samples from 17 NET patients and correlated with clinical response. In vivo, lanreotide therapy showed reduced effects on wnt, T cell receptor (TCR), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling in CD8+ T cells in responders compared to non-responders. Compared to non-responders, responders showed reduced effects on cytokine and chemokine signaling but greater effects on ubiquitination and proteasome degradation genes. Our results suggest significant lanreotide pharmacodynamic effects on immune function in vivo, which correlate with responses in NET patients. This is not evident from experimental in vitro settings.

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This study aimed to identify hub genes involved in regulatory T cell (Treg) function and migration, offering insights into potential therapeutic targets for cancer immunotherapy. We performed a comprehensive bioinformatics analysis using three gene expression microarray datasets from the GEO database. Differentially expressed genes (DEGs) were identified to pathway enrichment analysis to explore their functional roles and potential pathways. A protein-protein interaction network was constructed to identify hub genes critical for Treg activity. We further evaluated the co-expression of these hub genes with immune checkpoint proteins (PD-1, PD-L1, CTLA4) and assessed their prognostic significance. Through this comprehensive analysis, we identified CCR8 as a key player in Treg migration and explored its potential synergistic effects with ICIs. Our findings suggest that CCR8-targeted therapies could enhance cancer immunotherapy outcomes, with breast invasive carcinoma (BRCA) emerging as a promising indication for combination therapy. This study highlights the potential of CCR8 as a biomarker and therapeutic target, contributing to the development of targeted cancer treatment strategies.

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Innate immune cells, crucial in resisting infections and initiating adaptive immunity, play diverse and significant roles in tumor development. These cells, including macrophages, granulocytes, dendritic cells (DCs), innate lymphoid cells, and innate-like T cells, are pivotal in the tumor microenvironment (TME). Innate immune cells are crucial components of the TME, based on which various immunotherapy strategies have been explored. Immunotherapy strategies, such as novel immune checkpoint inhibitors, STING/CD40 agonists, macrophage-based surface backpack anchoring, ex vivo polarization approaches, DC-based tumor vaccines, and CAR-engineered innate immune cells, aim to enhance their anti-tumor potential and counteract cancer-induced immunosuppression. The proximity of innate immune cells to tumor cells in the TME also makes them excellent drug carriers. In this review, we will first provide a systematic overview of innate immune cells within the TME and then discuss innate cell-based therapeutic strategies. Furthermore, the research obstacles and perspectives within the field will also be addressed.

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This experiment examined how adding mannan-oligosaccharides (MOS) to the diet affected fertility, hatching rates, egg production, carcass characteristics, cost-effectiveness, and immune function in laying hens. One hundred and twenty Mandarah chickens (30 hens and 3 roosters per group) were randomly chosen between 34 and 50 wk old and divided into four groups. The first group was the control group, which was given just the basal diet. The basal diet was given to the second, third, and fourth experimental groups along with three different levels of MOS (0.1, 0.2, and 0.5 g/kg diet, respectively). Results found that hens fed MOS at various levels laid eggs at a significantly higher rate, enhanced egg number, egg mass and feed conversion ratio than the control group (P < 0.05). MOS seemed to improve carcass quality. The best results for egg quality (Haugh unit) and testosterone levels were seen with a dose of 0.5 g/kg of MOS compared to the control birds (P < 0.05). All MOS levels led to higher estradiol-17ß (E2) levels and better economic efficiency (EE). MOS also improved the hens' immune systems as compared to the control group. Hens-fed MOS had significantly greater levels of antibodies against Influenza viruses (H9N2) and Infectious Bronchitis Virus (P < 0.05). Also, the spleen and thymus gland, both crucial immune system components, were slightly larger (P < 0.05). It's important to note that fertility rates, hatchability, and embryo mortality rates remained similar across all groups. So, our findings suggest that incorporating MOS into the birds' diet enhances their productivity, strengthens their immune system, improves EE, and contributes to the overall health of the hens.

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Vaccines signify one of the economical and reasonable means to prevent and eradicate the important infectious diseases. Conventional vaccines like live attenuated and inactivated vaccines comprise of whole pathogen either in attenuated or killed form. While, new generation vaccines have been designed to elicit immune response by genetically modifying only the nucleic acid portion of that pathogen. These new generation therapeutics include mRNA vaccines, DNA plasmid vaccines, chimeric vaccines and recombinant viral vector-based vaccines. Nucleic acid based vaccines use genetic material itself thus, they are highly stable and potent in nature to induce long-lasting immune response. Amongst these novel vaccine platforms, viral vector-based vaccines is one such emerging field which has proven to be extremely effective and potent. Nowadays, veterinary medicine has also accepted this innovative vectored vaccine platform to develop an effective control strategy against certain important viral diseases of animals. Viral vector-based vaccine uses various DNA and RNA viruses of human or animal origin to carry an immunogenic transgene of target pathogen. These vaccines enhance both humoral and cell mediated immune response without use of any accessory immune-stimulants. Till today, several viruses have been modified to be characterized as vaccine vectors. Currently, large number of research programs are going on to develop vectored vaccines and novel viral vector for veterinary use. In the present review, different kinds of viral vectored vaccines having veterinary importance have been discussed.

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Breast cancer emerges as one of the most prevalent malignancies in women, its incidence showing a concerning upward trend. Among the diverse array of breast cancer subtypes, triple-negative breast cancer (TNBC) assumes notable significance, due to lack of estrogen, progesterone, and HER-2 receptors. More focus has to be placed on creating effective therapy due to the high prevalence and rising incidence of TNBC. Currently, conventional passive treatments have several drawbacks that have not yet been resolved. On the other hand, as innovative immunotherapy approaches, cancer vaccines have offered promising prospects in combatting advanced stages of TNBC. Therefore, the main objective of this study was to utilize WT1 and NY-ESO-1 antigenic proteins in designing a multiepitope vaccine against TNBC. Initially, to generate robust immune responses, we identified antigenic epitopes of both proteins and assessed their immunogenicity. In order to reduce junctional immunogenicity, promiscuous epitopes were joined using the suitable adjuvant (50S ribosomal L7/L12 protein) and incorporated appropriate linkers (GPGPG, AAY, and EAAAK). The best predicted 3D model was refined and validated to achieve an excellent 3D model. Molecular docking analysis and dynamic simulation were conducted to demonstrate the structural stability and integrity of the vaccine/TLR-4 complex. Finally, the vaccine was cloned into the vector pET28 (+). Thus, analysis of the constructed vaccine through immunoinformatics indicates its capability to elicit robust humoral and cellular immune responses in the targeted organism. As such, it holds promise as a therapeutic weapon against TNBC and may open doors for further research in the field.

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Purpose: Osteoarthritis (OA) is a prevalent cause of disability in older adults. Identifying diagnostic markers for OA is essential for elucidating its mechanisms and facilitating early diagnosis. Methods: We analyzed 53 synovial tissue samples (n = 30 for OA, n = 23 for the control group) from two datasets in the Gene Express Omnibus (GEO) database. We identified differentially expressed genes (DEGs) between the groups and applied dimensionality reduction using six machine learning algorithms to pinpoint characteristic genes (key genes). We classified the OA samples into subtypes based on these key genes and explored the differences in biological functions and immune characteristics among subtypes, as well as the roles of the key genes. Additionally, we constructed a protein-protein interaction network to predict small molecules that target these genes. Further, we accessed synovial tissue sample data from the single-cell RNA dataset GSE152805, categorized the cells into various types, and examined variations in gene expression and their correlation with OA progression. Validation of key gene expression was conducted in cellular experiments using the qPCR method. Results: Four genes AGMAT, MAP3K8, PER1, and XIST, were identified as characteristic genes of OA. All can independently predict the occurrence of OA. With these genes, the OA samples can be clustered into two subtypes, which showed significant differences in functional pathways and immune infiltration. Eight cell types were obtained by analyzing the single-cell RNA data, with synovial intimal fibroblasts (SIF) accounting for the highest proportion in each sample. The key genes were found over-expressed in SIF and significantly correlated with OA progression and the content of immune cells (ICs). We validated the relative levels of key genes in OA and normal cartilage tissue cells, which showed an expression trend consistency with the bioinformatics result except for XIST. Conclusion: Four genes, AGMAT, MAP3K8, PER1, and XIST are closely related to the progression of OA, and play as diagnostic and predictive markers in early OA.

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Introduction: This study aimed to evaluate the efficiency of tea polyphenols (TP) and medicinal plant mixtures (Astragalus membranaceus + Lonicera japonica, Rheum officinale Bail + Scutellaria baicalensis + Platycladus orientalis) combined with astaxanthin (AST), benzoic acid (BA), and yeast complex on the health status of Eriocheir sinensis. Method: A total of 630 crabs (male crabs: 41.51 ± 1.63 g; female crabs: 47.27 ± 0.79 g) were randomly distributed into seven groups with three replicates (male: female, 1:1). These crabs were fed as follows for 8 weeks: basal diet (M1), M2 (M1 + 100 mg/kg TP), M3 (M1 + 2.0 g/kg A. membranaceus + 20 g/kg L. japonica), M4 (M1 + 2.5 g/kg R. officinale Bail + 1.5 g/kg S. baicalensis + 1.0 g/kg P. orientalis), and M5, M6, M7 (M2, M3 and M4 with 600 mg/kg AST +1.0 g/kg BA + 20 mg/kg yeast complex added, respectively). Results and discussion: The results showed that the activities of acid phosphatase (ACP), alkaline phosphatase (AKP), and lysosome (LZM) in the hemolymph were significantly increased in M5, M6, and M7 (P < 0.05), and the highest phagocytosis index (PI) and LZM activity were observed in M7 of female crabs. Moreover, the antioxidant indicators superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT) of hepatopancreas were also significantly improved in M5, M6, and M7 (P < 0.05), while the malondialdehyde (MDA) contents showed an opposite trend. Furthermore, a morphological examination also showed the improved histological structure of hepatopancreas in M7, especially as seen in the clear lumens, no vacuolation, and integrity of the basal membrane of the hepatopancreatic tubule. Taken together, these results suggested that 2.5 g/kg R. officinale Bail, 1.5 g/kg S. baicalensis, and 1.0 g/kg P. orientalis in combination with 600 mg/kg AST, 1.0 g/kg BA, and 20 mg/kg yeast complex could improve the non-specific immunity, antioxidant capacity, and hepatopancreatic health of E. sinensis.

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CombiVacS study has demonstrated a strong immune response of the heterologous ChAdOx1-S/BNT162b2 vaccine combination. The primary outcomes of the study were to assess the humoral immune response against SARS-CoV-2, 28 days after a third dose of a mRNA vaccine, in subjects that received a previous prime-boost scheme with ChAdOx1-S/BNT162b2. Secondary outcomes extended the study to 3 and 6 months. The third vaccine dose of mRNA-1273 in naive participants previously vaccinated with ChAdOx1-S/BNT162b2 regimen reached higher neutralizing antibodies titers against the variants of concern Delta and BA.1 lineage of Omicron compared with those receiving a third dose of BNT162b2 at day 28. These differences between BNT162b2 and mRNA-1273 arms were observed against the ancestral variant G614 at day 90. Suboptimal neutralizing response was observed against BQ.1.1, XBB.1.5/XBB.1.9, and JN.1 in a relevant proportion of individuals 180 days after the third dose, even after asymptomatic Omicron breakthrough infections. EudraCT (2021-001978-37); ClinicalTrials.gov (NCT04860739).

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Background: Clearance of human papillomavirus (HPV) among adolescent men who have sex with men (MSM) is not well studied. This study aimed to evaluate the clearance of HPV DNA and antibodies among adolescent MSM. Methods: In our cohort study, we enrolled adolescent MSM in Melbourne between October 2010 and September 2013. At baseline, 3, 6, and 12 months, anal and penile swabs for HPV DNA and serum for HPV antibodies against genotypes 6, 11, 16, and 18, were collected. Definite clearance was defined as HPV DNA (same site) /antibodies for the same genotype undetected following a positive HPV DNA /antibodies test at baseline or month 3. Possible clearance was defined as HPV DNA (same site) /antibodies for the same genotype undetected at month 12 following a positive HPV DNA/antibodies test at month 6. Overall clearance was defined as either definite or possible clearance. The agreement between HPV DNA clearance and antibodies clearance was calculated. Results: A total of 183 MSM were included (median age: 19 years, interquartile [IQR]: 18 to 20). At the anus, overall clearance rate was 21.6 (95 % confidence interval[CI]: 7.9 to 47.0), 44.8 (19.3 to 88.3), 51.9 (20.9 to 106.9) and 33.7 (7.0 to 98.5) per 1000 person months (PM) for HPV 6, 11, 16 and 18. At the penis, overall clearance rate was 64.5 (13.3 to 188.5), 71.3 (14.7 to 208.2), 96.5 (31.3 to 225.3) and 333.3 (8.4 to 1857.2) per 1000 PM for HPV 6, 11, 16 and 18. For antibodies, overall clearance rate was 22.2 (9.6 to 43.7), 18.8 (3.9 to 55.0), 10.8 (0.3 to 60.1) and 19.0 (2.3 to 68.8) per 1000 PM. Agreement between anal/penile HPV DNA clearance and antibodies clearance was low: kappa = -0.18 (95 % CI: -0.28 to 0.08)/-0.13 (-0.24 to -0.02), 0.04 (-0.29 to 0.36)/0.22 (-0.32 to 0.76), -0.10 (-0.27 to 0.08)/-0.14 (-0.37 to 0.10) and -0.14 (-0.28 to 0.01)/-0.14 (-0.33 to 0.06) for HPV 6, 11, 16 and 18, respectively. Conclusion: Clearance rates of HPV DNA were low and varied by genotypes and anatomical sites among adolescent MSM. Antibodies against HPV were stable during the study period.

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Antinutritional factors in feedstuffs may limit their utilization in livestock production, but fermentation process can be used to improve feed quality; however, studies on fermented soybeans for laying hens remain limited. We investigated the effect of fermented soybean meal (FSBM) at various inclusion levels as a partial replacement for soybean meal (SBM) on egg production, egg quality, amino acid digestibility, gut morphology and microbiota, antioxidant capacity and immune response of young laying hens. A total of 360 Hy-line Brown laying hens aged 18 weeks were selected and divided into 5 groups of 6 replicates each and 12 birds per replicate. The control group received a basal diet while the trial group received the basal diet with FSBM included at 2.5%, 5.0%, 7.5% and 10.0%, respectively, for 12 weeks. Our findings revealed that the nutritional value of FSBM was higher compared to that of SBM in terms of reduced content of trypsin inhibitors and increased contents of crude protein, amino acids and minerals. FSBM enhanced egg production (P < 0.05), feed-to-egg ratio (P < 0.05), and albumen quality (albumen height and Haugh unit) (P < 0.05). Furthermore, FSBM improved apparent fecal amino acid digestibility (P < 0.05), gut morphology (increased villus height, villus width, villus height-to-crypt depth ratio and decreased crypt depth) (P < 0.05), antioxidant capacity (reduced malondialdehyde and increased catalase, total superoxide dismutase, glutathione peroxidase and total antioxidant capacity) (P < 0.05) and immune function (increased concentrations of IgG, IgA, and IgM; increased levels of transforming growth factor beta and Toll-like receptor 2; and reduced levels of interleukin 1ß and tumor necrosis factor alpha) (P < 0.05). Further analysis showed that FSBM altered the composition of the gut microbiota favoring beneficial microbes. These findings suggest that probiotic fermentation improved the nutritional value of SBM. The inclusion of FSBM in the diets of laying hens at 2.5% or 5.0% improved amino acid digestibility, gut health, immune function, egg production and egg quality.

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OBJECTIVE: Acute myeloid leukemia (AML) is a malignant clonal proliferative disease with a high mortality rate. The combination therapy of BCL-2 inhibitor Venetoclax (VEN) and hypomethylating agents (HMAs) has significant anti-leukemia activity. METHODS: We analyzed the efficacy, safety and immune response characteristics of AML patients who were unfit for high-dose chemotherapy and accepted the medication of VEN + HMAs. RESULTS: After VEN + HMAs treatment, 31 newly diagnosed AML patients had the morphologic leukemia-free state rate (MLFS%) of 80.6% (25/31), complete response rate (CR%) of 54.8% (17/31), the minimal residual disease negative rate (MRD-%) of 51.6% (16/31), and the median progression-free survival (PFS) of 14 months. After treatment, the proportion of bone marrow primitive cells, the MRD level, white blood cell (WBC) count, fibrinogen (FIB) level and the proportion of B cells were significantly decreased. The red blood cell (RBC) count, hemoglobin (HGB) level, platelet count (PLT) count, activated partial thromboplastin time (APTT), the proportion of total T cells, CD8 + T cells and the IFN-γ level were significantly increased. After VEN + HMAs treatment, 12 relapsed AML patients had a MLFS% of 50% (6/12), CR% of 33.3% (4/12), MRD-% of 25% (3/12), and a median PFS of 7 months. After treatment, the proportion of bone marrow primitive cells and MRD level were slightly decreased, the proportions of CD8 + T cells and NK cells were significantly increased, the proportion of B cells and IL-10 level were significantly decreased. 12 AML patients who receive microtransplantation (MST) treatment using VEN + HMAs as a pretreatment regimen had a PFS of 20.5 months, which was much greater than VEN + HMAs group alone. Hematological recovery was better in the MST group with significantly increased RBC count, HGB level and PLT count. The most common adverse events were myelosuppression, agranulocytosis, infection and cardiovascular toxicity. No fatal adverse events were reported. CONCLUSION: The combination of BCL-2 inhibitors and HMAs had good efficacy and safety in AML patients who were unfit for high-dose chemotherapy, which may improve the immune microenvironment and enhance anti-leukemia immune response.

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Tumor-associated neutrophils (TANs) have been shown to promote immunosuppression and tumor progression, and a high TAN frequency predicts poor prognosis in triple-negative breast cancer (TNBC). Dysregulation of CREB binding protein (CBP)/P300 function has been observed with multiple cancer types. The bromodomain (BRD) of CBP/P300 has been shown to regulate its activity. In this study, we found that IACS-70654, a novel and selective CBP/P300 BRD inhibitor, reduced TANs and inhibited the growth of neutrophil-enriched TNBC models. In the bone marrow, CBP/P300 BRD inhibition reduced the tumor-driven abnormal differentiation and proliferation of neutrophil progenitors. Inhibition of CBP/P300 BRD also stimulated the immune response by inducing an IFN response and MHCI expression in tumor cells and increasing tumor-infiltrated cytotoxic T cells. Moreover, IACS-70654 improved the response of a neutrophil-enriched TNBC model to docetaxel and immune checkpoint blockade. This provides a rationale for combining a CBP/P300 BRD inhibitor with standard-of-care therapies in future clinical trials for neutrophil-enriched TNBC.

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This work establishes the design of a fully synthetic, shear-thinning hydrogel platform that is injectable and can isolate engineered, allogeneic cell therapies from the host. We utilized RAFT to generate a library of linear random copolymers of N,N-dimethylacrylamide (DMA) and 2-vinyl-4,4-dimethyl azlactone (VDMA) with variable mol% VDMA and degree of polymerization. Poly(DMA-co-VDMA) copolymers were subsequently modified with either adamantane (Ad) or ß-cyclodextrin (Cd) through amine-reactive VDMA to prepare hydrogel precursor macromers containing complementary guest-host pairing pendant groups that, when mixed, form shear-thinning hydrogels. Rheometric evaluation of the hydrogel library enabled identification of lead macromer structures comprising 15 mol% pendants (Ad or Cd) and a degree of polymerization of 1000; mixing of these Ad and Cd functionalized precursors yielded hydrogels possessing storage modulus above 1000 Pa, tan(δ) values below 1 and high yield strain, which are target characteristics of robust but injectable shear-thinning gels. This modular system proved amenable to nanoparticle integration with surface-modified nanoparticles displaying Ad. The addition of the Ad-functionalized nanoparticles simultaneously improved mechanical properties of the hydrogels and enabled extended hydrogel retention of a model small molecule in vivo. In studies benchmarking against alginate, a material traditionally used for cell encapsulation, the lead hydrogel showed significantly less fibrous encapsulation in a subcutaneous implant site. Finally, this platform was utilized to encapsulate and extend in vivo longevity of inducible transgene-engineered mesenchymal stem cells in an allogeneic transplant model. The hydrogels remained intact and blocked infiltration by host cells, consequently extending the longevity of grafted cell function relative to a benchmark, shear-thinning hyaluronic acid-based gel. In sum, the new synthetic, shear-thinning hydrogel system presented here shows potential for further development as an injectable platform for delivery and in situ drug modulation of allograft and engineered cell therapies.

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The bacterium Mycoplasma hyopneumoniae (Mhp) causes a chronic infectious respiratory disease in pigs, leading to important economic losses. This study aimed to compare the immune response of the local Piau breed and a commercial line to Mhp vaccination. For this, two phases were carried out. In the first, gene expression of toll-like receptors (TLR2, TLR4, TLR6, and TLR10) and cytokines (IL2, IL6, IL8, IL10, IL12, IL13, TNFα, and TGFß) was assessed in porcine blood mononuclear cells (PBMC) from the two genetic groups before and after vaccination. In the second experiment, nitric oxide production, specific antibodies, and gene expression of toll-like receptors and cytokines were evaluated in bronchoalveolar lavage fluid (BALF) cells of vaccinated and unvaccinated pigs. After vaccination against Mhp, TLR2, TLR4, TLR6, TLR10, IL6, TNFα, and TGFß expression levels were elevated in PBMC from commercial animals, and TLR6, TLR10, and TGFß expression levels were elevated in PBMC from the Piau group. Vaccination also increased the production of Mhp-specific IgG antibodies in BALF cells in the Piau breed. Comparison of the two genetic groups revealed differences in TNFα and IL10 expression in BALF cells. These results show that Piau pigs have different immune responses to vaccination compared with commercial animals. It is worth noting that these genetic differences between both genetic groups may be related to phenotypic differences in Mhp resistance or susceptibility.

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Co-infection with Clonorchis sinensis (C. sinensis) and Hepatitis B virus (HBV) are commonly observed in endemic areas of Clonorchiasis. Chronic infection of C. sinensis or HBV is more likely to happen. However, the immune mechanisms related to the pathogenesis of co-infection remain unknown. In the present study, Myeloid-derived suppressor cells (MDSCs) accumulation, bone marrow derived dendritic cells (BMDCs) reaction and the consequent effectors on Th1/Th2 polarization to co-incubation of excretory-secretory products from C. sinensis (CsESP) and Hepatitis B e antigen (HBeAg) in vitro were investigated for further understanding the immune response during co-infection. The results indicated that compared with CsESP or HBeAg alone, co-stimulation dominantly promoted MDSCs accumulation. Co-stimulation significantly downregulated the expression of CD80 and CD86, and reduced IL-12p70 release while augmented IL-10 levels of BMDCs. Higher transcription levels of mannose receptor (MR) while lower mRNA level of toll like receptor 4 (TLR-4) were detected among membrane receptors of BMDCs with co-treatment. In addition, after CD4 naïve T cells were stimulated by LPS-treated BMDCs with CsESP and HBeAg, the proportion of CD4+IL-4+ T cells and IL-4 increased, while CD4+INF-γ+ T cells percentage and INF-γ down-regulated. In conclusion, CsESP and HBeAg co-incubation more distinctly suppressed maturation of BMDCs resulting in increase of IL-10 and decrease of IL-12 highly possible by up-regulation of MR and down-regulation of TLR-4 of BMDCs, and successively induce Th2 immune skewing. These findings laid the cornerstone to further clarify immune responses during the co-infection contributing to the better precise treatment and progression assessment of co-infection patients.

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Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of proline- and glutamine-rich proteins, widely termed "gluten", in genetically susceptible individuals. CD induces an altered immune response that leads to chronic inflammation and duodenal mucosal damage. Currently, there are no specific tests for the accurate diagnosis of CD, and no drugs are available to treat this condition. The only available treatment strategy is lifelong adherence to a gluten-free diet. However, some studies have investigated the involvement of microRNAs (miRNAs) in CD pathogenesis. miRNAs are small noncoding ribonucleic acid molecules that regulate gene expression. Despite the growing number of studies on the role of miRNAs in autoimmune disorders, data on miRNAs and CD are scarce. Therefore, this study aimed to perform a literature review to summarize CD, miRNAs, and the potential interactions between miRNAs and CD in adults. This review shows that miRNA expression can suppress or stimulate pathways related to CD pathogenesis by regulating cell proliferation and differentiation, regulatory T-cell development, innate immune response, activation of the inflammatory cascade, focal adhesion, T-cell commitment, tissue transglutaminase synthesis, and cell cycle. Thus, identifying miRNAs and their related effects on CD could open new possibilities for diagnosis, prognosis, and follow-up of biomarkers.

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Liver failure profoundly affects the immune system, leading to dysregulation of innate and adaptive immune response. This review explores the intricate relationship between liver function and immune homeostasis. The role of the liver as a central hub in immune response initiation is elucidated, emphasizing its involvement in hepatic inflammation induction and subsequent systemic inflammation. Cytokines, chemokines, growth factors, and lipid mediators orchestrate these immune processes, serving as both prognostic biomarkers and potential therapeutic targets in liver failure-associated immune dysregulation, which might result from acute-on-chronic liver failure (ACLF) and cirrhosis. Furthermore, the review delves into the mechanisms underlying immunosuppression in liver failure, encompassing alterations in innate immune cell functions such as neutrophils, macrophages, and natural killer cells (NK cells), as well as perturbations in adaptive immune responses mediated by B and T cells. Conclusion: Understanding the immunological consequences of liver failure is crucial for developing targeted therapeutic interventions and improving patient outcomes in liver disease management.

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