Expression Of Immune-related Genes Research Articles

Escherichia coli heat-labile enterotoxin B subunit as an adjuvant of mucosal immune combined with GCRV-II VP6 triggers innate immunity and enhances adaptive immune responses following oral vaccination of grass carp (Ctenopharyngodon idella)

The grass carp reovirus (GCRV) is the most major pathogen that has threatened the grass carp (Ctenopharyngodon idella) industry of China for years. Though the oral vaccine has many advantages, the current vaccines still do not provide complete protection. Therefor the exploration of new preventive strategies is urgently needed. In this study, heat-labile enterotoxin B subunit of Escherichia coli (LTB) was combined with VP6 from GCRV type II (GCRV-II) via Lactococcus lactis expression system to form a potent oral vaccine and determines if fusion of LTB to the protective vaccine antigen can enhance protection in the fish. The expression of recombinant protein was confirmed by Western-blotting and enzyme-linked immunosorbent assay. The rare minnow was set as the model for the evaluation of the experiment administrated orally. The immune response including the antibody titer and the immune-related gene expression, and the protective efficacy which included the virus loaded and the relative protection, were thoroughly investigated after the trial. The results indicated that LTB can significantly elicit a higher neutralizing antibody responses and enhanced T-cell priming, activities and proliferation in mononuclear cells from intestine, spleen and kidney tissues when compared to the VP6 vaccine alone. Moreover, the combined adjuvant can significantly up-regulate type I interferon signaling in different immune organs, especially the mucosa associated lymphoidtissue which could not be induced by VP6 along, result in the contribution of the improvement in adaptive immune responses of the fish. In addition, challenge study showed that LTB combined VP6 could greatly improve the relative percent survival of the fish during the virus infection. These results highlight that LTB has the potential value to be a mucosal adjuvant of the fish, approaching for improving the efficacy of vaccination against GCRV-II, which does elicit both non-specific and specific immune responses.

Evaluation of a Low-Temperature Immersion Immunization Strategy for the Infectious Spleen and Kidney Necrosis Virus orf037l Gene-Deleted Attenuated Vaccine

Background: Infectious spleen and kidney necrosis virus (ISKNV) poses a significant threat to aquaculture sustainability, particularly affecting mandarin fish (Siniperca chuatsi) and causing significant economic losses. Methods: To address this challenge, this study developed an ISKNV Δorf037l vaccine strain, where the orf037l gene was knocked out. Infection assays conducted at 28 °C showed that the knocking out the orf037l gene decreased the virulence of ISKNV and reduced lethality against mandarin fish by 26.7% compared to wild-type ISKNV. To further diminish residual virulence, the effect of low-temperature (22 °C) immersion immunization was evaluated. Results: The results indicate that low temperature significantly diminished the virulence of the Δorf037l vaccine strain, elevating the survival rate of mandarin fish to 90%. Furthermore, the vaccine strain effectively triggered the expression of crucial immune-related genes, such as IFN-h, IL-1, IκB, Mx, TNF-α, and Viperin, while inducing the production of specific neutralizing antibodies. Low-temperature immersion with Δorf037l achieved a high relative percentage of survival of 92.6% (n = 30) in mandarin fish, suggesting the potential of Δorf037l as a promising immersion vaccine candidate. Conclusions: These findings contribute to advancing fish immersion vaccine development and demonstrate the importance and broad applicability of temperature optimization strategies in vaccine development. Our work carries profound implications for both the theoretical understanding and practical application in aquaculture disease control.

New insights into transcriptional and metabolic differences between pregnant males and embryos in seahorses

Seahorses exhibit a unique reproduction mode of male pregnancy. Successful gestation plays a crucial role in the seahorse reproduction process and the aquaculture industry. However, the substantial paternal-embryo differences in seahorses remain largely unexplored. In the present study, transcriptomic and metabolic differences between pregnant males and embryos during gestation were explored to investigate the roles of key genes and metabolites in pregnant males and embryos in seahorses. Higher levels of essential amino acids and polyunsaturated fatty acids in embryos compared to fathers may indicate their vital role in embryonic development. The high expression of immune-related genes (CCLs and CCRs) and downregulation of antioxidants in fathers may provide immune protection and reduce the immunological rejection of embryos during gestation. The transcript-metabolite correlation network during pregnancy further indicated the role of key genes and metabolites during embryonic eye (N-acetyl-L-histidine, PAX6, and FZT4) and tail (WNT5 and WNT8) development. The findings of the present study not only provide valuable data on differences between pregnant males and embryos in seahorse, but also lay foundation for future research on seahorse aquaculture.

Effects of silybin on growth performance, antioxidant capacity and immunity in juvenile hybrid grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂) fed with high-lipid diets

This research examined the impacts of varying silybin dosages in high-lipid diets on the growth, hepatic histology, immunity, and immune-related gene expression of juvenile hybrid grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂). The grouper (with an initial body weight of 8.27 ± 0.08 g) were fed diets containing silybin at levels of 0 g/kg (S1, control group), 0.05 g/kg (S2), 0.10 g/kg (S3), 0.15 g/kg (S4), 0.20 g/kg (S5), 0.25 g/kg (S6), and 0.50 g/kg (S7) for 8 weeks. The study results suggest that the silybin-treated groups displayed an initial increase followed by a decrease in final body weight and specific growth rate, with the highest value observed in the group S5. In serum samples, silybin supplementation of high-lipid diets resulted in increased activities of alkaline phosphatase (AKP), superoxide dismutase (SOD) and catalase (CAT) enzymes, decreased activities of aspartate transaminase (AST) and alanine transaminase (ALT) enzymes and increased total antioxidant capacity (T-AOC) content. In liver, the addition of silybin to high-lipid diets increased SOD, CAT, and lysozyme (LYZ) enzyme activities, increased T-AOC and immunoglobulin M (IgM) contents, and decreased reactive oxygen species (ROS) and malondialdehyde (MDA) contents. Contrasted with the control group, the addition of silybin at 0.05–0.50 g/kg enhanced the hepatic histomorphology, for example, ameliorating the indistinctness of cell outlines and diminishing the hepatocyte vacuolation. Silybin treatment significantly upregulated the expression of liver sod, cat, gpx, nrf2, keap1, hsp70, hsp90, tlr22, myd88, il-1β, tnf-α and il-6(P < 0.05). Silybin treatment significantly upregulated the expression of tlr22, myd88, il-1β, tnf-α, and il-6 of head kidney (P < 0.05). After vibrio harveyi challenge, groups S5-S6 showed higher survival than the control. Incorporating silybin into high-lipid diets boosts grouper's growth, antioxidant, and immune abilities. Regression analysis implies adding 0.23 g/kg silybin to the diets of juvenile hybrid grouper.

The Immune Defense Response and Immune-Related Genes Expression in Macrobrachium nipponense Infected with Decapod Iridescent Virus 1 (DIV1).

Macrobrachium nipponense is a significant cultivated species in China. However, decapod iridescent virus 1 (DIV1), as a newly discovered crustacean-lethal virus, has resulted in significant financial losses for the M. nipponense industry. In order to examine the immunological response of M. nipponense to DIV1, we conducted transcriptome analysis of the hepatopancreas from M. nipponense infected with DIV1 using RNA-seq. RNA sequencing analysis identified a combined total of 41,712 assembled unigenes, and 7014 genes that showed differential expression were identified in the group infected with DIV1, compared to the control group. Among these DEGs, 3952 were found to be up-regulated, while 3062 were down-regulated; many well-characterized DEGs were involved in innate immune defense, particularly involving the C-type lectin receptor signaling pathway, complement and coagulation cascades, phagosome, lysosome and PPAR signaling pathway. Moreover, the expression levels of well-known immune-related genes (dorsal, wnt6, lectin, caspase, integrin, hsp70) in the hepatopancreas and hemolymph were investigated by Quantitative real-time PCR (qRT-PCR), and the findings demonstrated a significant increase in gene expression in the hepatopancreas and hemolymph at various time points after infection. The results acquired in this study offered further comprehensive understanding of the immunological response of M. nipponense to DIV1 infection.

Immunomodulatory and growth promotors effects of rosemary (Rosmarinus officinalis) and/or Spirulina with respect to some gene expression on Nile tilapia (Oreochromis niloticus) in Aswan Governorate

The purpose of this work trial was to determine the true impact of spirulina and rosemary in a combination treatment on Nile tilapia performance before experimental infection. Moreover, the effects of these treatments on the liver and kidney functions, the histology of certain organs, and the expression of certain antioxidant and immune-related genes in the liver tissue both before and after Aeromonas hydrophila (A. hydrophila) infection are also included. To achieve this purpose, four diets were prepared: the first was free of additives as a control group (Con), the second contained (SP) spirulina at 7.5 g/kg of diet, the third contained (RM) rosemary at a rate of 10 g/kg of diet, and the fourth one contained rosemary and spirulina as a SP + RM group. The results of the different parameters indicated the growth-stimulant effects of rosemary and spirulina either alone or in a combination when compared with the control group (P ≤ 0.05), with a superior effect to combination treatment. In addition, improved hematological parameters, immunological assays, phagocytic activity and index, and expression of antioxidant and immune-related genes occurred before and after infection. Moreover, there were positive effects of spirulina and rosemary without pathological lesions in the different organs before infection and fewer lesions after infection.

STING induces HOIP-mediated synthesis of M1 ubiquitin chains to stimulate NFκB signaling.

STING activation by cyclic dinucleotides in mammals induces IRF3- and NFκB -mediated gene expression, and the lipidation of LC3B at Golgi-related membranes. While mechanisms of the IRF3 response are well understood, the mechanisms of NFκB activation mediated by STING remain unclear. We report that STING activation induces linear/M1-linked ubiquitin chain (M1-Ub) formation and recruitment of the LUBAC E3 ligase, HOIP, to LC3B-associated Golgi membranes where ubiquitin is also localized. Loss of HOIP prevents formation of M1-Ub ubiquitin chains and reduces STING-induced NFκB and IRF3-mediated signaling in human monocytic THP1 cells and mouse bone marrow derived macrophages, without affecting STING activation. STING-induced LC3B lipidation is not required for M1-Ub chain formation or the immune-related gene expression, however the recently reported function of STING to neutralize the pH of the Golgi may be involved. Thus, LUBAC synthesis of M1 ubiquitin chains mediates STING-induced innate immune signaling.

Dietary Artichoke (Cynara scolymus) Extract Ameliorated the Growth Performance, Humoral Immune Parameters and Resistance Against Aeromonas hydrophila in Goldfish (Carassius auratus)

Abstract This trial investigated the efficacy of artichoke (Cynara scolymus) extract (AE) on the growth performance, immunity, antioxidant parameters, and resistance against Aeromonas hydrophila of goldfish (Carassius auratus). For this purpose, a total number of 470 goldfish with initial weight 5.70±0.2 g were fed with four experimental diets including 0 (T0), 100 (T1), 150 (T2), and 200 (T3) mg kg−1 diet AE for 8 weeks. At the end of feeding trial, growth performances, serum immune parameters, and mucus antioxidant enzymes were measured. Fish were challenged with A. hydrophila, and the antioxidant and immunity-related gene expression were investigated. Based on the results, the highest final weight (FW) and weight gain (WG) were attained in T2 and T3 (P&lt;0.05). Immune factors including ACH50, lysozyme, and total immunoglobulin in T2 and T3 showed the highest values (P&lt;0.05). The expression of GR, IL1 β, TNF α, HSC70, HSP70, and HSP90 β genes in T1, T2, and T3 were higher than the control (P&lt;0.05). The GST expression was significantly enhanced in T2 (P&lt;0.05). The present study demonstrated that the administration of AE, especially at doses of 150 mg kg−1, could improve the growth, immunity, and antioxidant parameters, as well as enhance disease resistance against A. hydrophila in goldfish.

Dietary Lithospermum erythrorhizon ethanol extract alleviates soybean meal-induced enteritis by improving immune tolerance profile of pearl gentian grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂)

The aquaculture industry has a shortage of objected protection against soybean meal-induced enteritis (SBMIE) in carnivorous fish caused by soybean meal feed. Our initial study discovered that Lithospermum erythrorhizon (LE) ethanol extract has potential application value in improving SBMIE. A feeding trial (for eight weeks) was conducted to investigate LE ethanol extract on pearl gentian grouper SBMIE of protection to clarify the influence of LE ethanol extract on the immune tolerance profile. Three hundred and sixty pearl gentian groupers were administered one of three distinct dietary regimes: 1) 100 % fish meal (FM); 2) soybean meal substitution of 50 % fish meal protein (SBM); 3) SBM diet +0.2 % LE ethanol extract (SBMLE). Each treatment included three 1000 L cisterns—each of cisterns with 30 fish. The preliminary weight of the fish varied between 72.01 g and 72.50 g. Growth performance results showed that WGR and SGR were significantly decreased in the SBM group (P < 0.05), while there was no significant difference between the FM and SBMLE groups. There was no significant difference in survival among the three groups. The results showed that SBM-fed fish exhibited enteritis manifested by mucosal fold shortening, lamina propria widening, decreased serum immune markers (IgM, C3, and C4), and up-regulated expression of pro-inflammatory cytokines (il17 and il12) and immune-related gene (tlr3, and tlr9). The addition of 0.2 % LE ethanol extract to the SBM diet, reversed the above symptoms, and anti-inflammatory cytokine (tgf-β1), gene expression increased significantly (P < 0.05). Intestinal transcriptome analysis exhibited that the DEGs between the FM group and the SBM group were mainly enriched in FoxO signaling pathway, while the DEGs between the SBM group and the SBMLE group were enriched in MAPK signaling pathway and FoxO signaling pathway. The RT-qPCR results also revealed changes in MAPK/FoxO signaling pathway-related genes, including Dusp1, jund, Irs2b, fbxo32, and ccng2. Overall, Lithospermum erythrorhizon ethanol extract may alleviate SBMIE by regulating MAPK/FoxO signaling pathway, which would be beneficial for enhancing the immune tolerance and utilization efficiency of pearl gentian groupers to dietary soybean meal.

Characterization of prognostic signature related with twelve types of programmed cell death in lung squamous cell carcinoma

ObjectiveThis study aimed to develop a prognostic cell death index (CDI) based on the expression of genes related with various types of programmed cell death (PCD), and to assess its clinical relevance in lung squamous cell carcinoma (LUSC).MethodsPCD-related genes were gathered and analyzed in silico using the transcriptomic data from the LUSC cohorts of The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Differentially expressed PCD genes were analyzed, and a prognostic model was subsequently constructed. CDI scores were calculated for each patient, and their correlations with clinical features, survival outcomes, tumor mutation burden, gene clusters, and tumor microenvironment were investigated. Unsupervised consensus clustering was performed based on CDI model genes. Furthermore, the correlation of CDI for sensitivity of targeted drugs, chemotherapy efficacy, and immunotherapy responses was assessed.ResultsBased on 351 differentially expressed PCD genes in LUSC, a CDI signature comprising FGA, GAB2, JUN, and CDKN2A was identified. High CDI scores were significantly associated with poor survival outcomes (p < 0.05). Unsupervised clustering revealed three distinct patient subsets with varying survival rates. CDKN2A exhibited significantly different mutation patterns between patients with high and low CDI scores (p < 0.01). High CDI scores were also linked to increased immune cell infiltration of specific subsets and altered expression of immune-related genes. Patients with high-CDI showed reduced sensitivity to several chemotherapeutic drugs and a higher Tumor Immune Dysfunction and Exclusion (TIDE) score, indicating potential resistance to immunotherapy.ConclusionThe CDI signature based on PCD genes offers valuable prognostic insights into LUSC, reflecting molecular heterogeneity, immune microenvironment associations, and potential therapeutic challenges. The CDI holds potential clinical utility in predicting treatment responses and guiding the selection of appropriate therapies for patients with LUSC. Future studies are warranted to further validate the prognostic value of CDI in combination with clinical factors and to explore its application across diverse patient cohorts.

Exploring the molecular landscape of cancer of unknown primary: A comparative analysis with other metastatic cancers.

Cancer of unknown primary (CUP) tumors are biologically very heterogeneous, which complicates stratification of patients for treatment. Consequently, these patients face limited treatment options and a poor prognosis. With this study, we aim to expand on the current knowledge of CUP biology by analyzing two cohorts: a well-characterized cohort of 44 CUP patients, and 213 metastatic patients with known primary. These cohorts were treated at the same institution and characterized by identical molecular assessments. Through comparative analysis of genomic and transcriptomic data, we found that CUP tumors were characterized by high expression of immune-related genes and pathways compared to other metastatic tumors. Moreover, CUP tumors uniformly demonstrated high levels of tumor-infiltrating leukocytes and circulating Tcells, indicating a strong immune response. Finally, the genetic landscape of CUP tumors resembled that of other metastatic cancers and demonstrated mutations in established cancer genes. In conclusion, CUP tumors possess a distinct immunophenotype that distinguishes them from other metastatic cancers. These results may suggest an immune response in CUP that facilitates metastatic tumor growth while limiting growth of the primary tumor.

Transcriptomic response of Hermetia illucens L. (Diptera: Stratiomyidae) to wounding and Gram-negative bacterial infection

Abstract The larvae of the black soldier fly (BSFL), Hermetia illucens L. (Diptera: Stratiomyidae), are of economic interest due to their use as livestock feed component. Unraveling their response to a bacterial infection will allow us to gain a better insight into their biology. In the current study, we used RNA-Seq analysis to unravel the transcriptomic response of BSFL to wounding and infection by a Gram-negative bacterium, Pseudomonas protegens Pf-5. Five-day-old BSFL were subjected to three treatments, i.e. untreated, PBS-injection, and bacteria-injection (5000 CFU per larva) and samples were collected at three time points (2 h, 6 h, and 13 h) post- treatment. Wounding induced expression of genes encoding recognition molecules and signaling pathway genes such as PGRP-SA, and Relish, and antimicrobial peptides (AMPs) such cecropin, defensin, and attacin. At 2 h, wounding resulted in a significant upregulation of immunity-related genes whereas genes encoding for resilin and cuticle proteins were significantly downregulated. At 6 h, the expression of immunity-related genes reduced in response to wounding whereas their expression increased in infected larvae. At 13 h, the expression of immunity-related genes reduced drastically in response to wounding, while their expression increased significantly in infected larvae. Conversely, the expression of metabolism-related genes, such as trypsin and chymotrypsin, was significantly upregulated in wounded larvae at 13 h, while their expression was significantly reduced in infected larvae. Increased investments in immunity-related processes in infected BSF larvae correlated with the downregulation of genes associated with metabolic processes indicative of a trade-off. Various immunity-related genes, including those encoding cecropin, defensin, attacin, and PGRP-SA, were consistently induced only during pathogen infection, indicating their role in immunity against Gram-negative bacteria. In this study, we report multiple genes that are significantly upregulated post-bacterial infection in BSFL that may be utilized as biomarkers to monitor insect health in mass production facilities.

Three hepcidins from the spotted knifejaw (Oplegnathus punctatus) promote antimicrobial activity via TLR/NFκB pathway

Hepcidin belongs to a class of small cationic antimicrobial peptides rich in cysteine. It is synthesized by liver and is widely involved in host antimicrobial, antiviral and other immune responses. We identified and characterized three hepcidin genes (OpHep1, OpHep2 and OpHep3) in spotted knifejaw. All the OpHeps shared high identities with hepcidins in other teleost, containing alpha helix and β-sheets. Three OpHeps were all detected in healthy tissues, with the abundant expression in liver. They were significantly increased after Vibrio harveyi infection in the six immune-relevant tissues (liver, kidney, spleen, gill, skin and intestine). OpHeps knockdown in spotted knifejaw liver cells affected the mRNA levels of inflammation-related genes, including il1β, il6, il8, and nfκb. Further, the recombinant hepcidin proteins were effective in suppressing the growth of both Gram-negative and Gram-positive bacteria. To identify the function of OpHeps in vivo, we performed the overexpression of three OpHeps in zebrafish, and found OpHeps could significantly induce immune-related genes expression in transgenic zebrafish, including myd88, il10, il21, il16, tlr1, tlr3 and lysozyme. When infected with V. harveyi, OpHeps transgenic zebrafishes had a higher survival rate than wild-type zebrafishes. The expression of myd88, il10, il8, il1β, nfκb and lysozyme were all significantly up-regulated in transgenic fishes during bacterial infection. In summary, these results indicated that hepcidin could protect fish fight against pathogen through TLR/NFκB signaling cascade and Lysozyme. Three OpHeps would be potential targets for prevention of bacterial infections in aquaculture industry of spotted knifejaw, which provided a new idea for the molecular breeding of fish disease resistance.

Tailoring Escalation Adjuvant Therapy for Early-Stage Triple-Negative Breast Cancer in the CBCSG010 Clinical Trial Biomarker Analysis.

Triple-negative breast cancer (TNBC) is a highly heterogeneous disease. The CBCSG010 trial is a prospective and multicenter phase III clinical trial confirming that adding adjuvant capecitabine significantly improved the 5-year disease-free survival (DFS) rate in patients with TNBC by 5.9%. In this study, we attempted to identify the specific population that benefited from adjuvant therapy. In this retrospective exploratory analysis, we performed RNA sequencing of tumor tissues from patients with TNBC in the CBCSG010 clinical trial. A single-sample gene set enrichment analysis algorithm and survival analysis were performed to characterize the intrinsic molecular features of the TNBC microenvironment and assess the associations between immune-related gene expression levels or immune cell counts with capecitabine treatment efficacy. Additionally, we performed immunohistochemical staining of 2 markers, PD-L1 and CD8, and hematoxylin-eosin staining of stromal tumor-infiltrating lymphocytes (sTILs) on formalin-fixed, paraffin-embedded specimens to validate findings from bioinformatics analyses. We found that patients with TNBC with high immune-infiltration treated with capecitabine were more likely to have a better prognosis. We used a cutoff of ≥25 combined positive score (CPS) of PD-L1, ≥10% positive sTILs, and ≥10% positive cells of CD8 to define the "immune-hot" patients. Among immune-hot patients, Kaplan-Meier curves showed that 5-year DFS rates were 96.9% and 79.4% in the capecitabine and control groups, respectively (hazard ratio, 0.13; 95% CI, 0.03-0.52; P=.049 in favor of capecitabine). In the capecitabine group, the 5-year DFS rate was higher for immune-hot patients than for immune-cold patients (96.9% vs 76.4%; hazard ratio, 0.11; 95% CI, 0.04-0.29; P=.028). Our study suggested that immune-hot patients with TNBC are more likely to benefit from adjuvant capecitabine, and that combining immunotherapy with chemotherapy may be expected to be more effective in immune-hot patients.

Effects of passion fruit peel (Passiflora edulis) pectin and red yeast (Sporodiobolus pararoseus) cells on growth, immunity, intestinal morphology, gene expression, and gut microbiota in Nile tilapia (Oreochromis niloticus)

This study explores the effects of dietary supplementation with passion fruit peel pectin (Passiflora edulis) and red yeast cell walls (Sporidiobolus pararoseus) on growth performance, immunity, intestinal morphology, gene expression, and gut microbiota of Nile tilapia (Oreochromis niloticus). Nile tilapia with an initial body weight of approximately 15 ± 0.06 g were fed four isonitrogenous (29.09–29.94%), isolipidic (3.01–4.28%), and isoenergetic (4119–4214 Cal/g) diets containing 0 g kg−1 pectin or red yeast cell walls (T1 - Control), 10 g kg−1 pectin (T2), 10 g kg−1 red yeast (T3), and a combination of 10 g kg−1 pectin and 10 g kg−1 red yeast (T4) for 8 weeks. Growth rates and immune responses were assessed at 4 and 8 weeks, while histology, relative immune and antioxidant gene expression, and gut microbiota analysis were conducted after 8 weeks of feeding. The results showed that the combined supplementation (T4) significantly enhanced growth performance metrics, including final weight, weight gain, specific growth rate, and feed conversion ratio, particularly by week 8, compared to T1, T2, and T3 (P < 0.05). Immunological assessments revealed increased lysozyme and peroxidase activities in both skin mucus and serum, with the T4 group showing the most pronounced improvements. Additionally, antioxidant and immune-related gene expression, including glutathione peroxidase (GPX), glutathione reductase (GSR), and interleukin-1 (IL1), were upregulated in the gut, while intestinal morphology exhibited improved villus height and width. Gut microbiota analysis indicated increased alpha and beta diversity, with a notable rise in beneficial phyla such as Actinobacteriota and Firmicutes in the supplemented groups. These findings suggest that the combined use of pectin and red yeast cell walls as prebiotics in aquaculture can enhance the health and growth of Nile tilapia, offering a promising alternative to traditional practices. Further research is needed to determine optimal dosages for maximizing these benefits.

Cosmetic implant placement in the female breast yields an altered local and systemic immune response: evidence for breast cancer immunosurveillance.

Women with cosmetic implants have lower rates of future breast cancer than the general population. We hypothesized the implant foreign body response could induce a local protective anti-cancer immunosurveillance. We expanded on our previous finding which showed women with breast implants have elevated antibody responses to certain breast cancer proteins. Blood samples and breast tissue were collected from women undergoing first time breast augmentation (implant-naive, IN) and revision breast augmentation (implant-exposed, IE). Sera were collected and antibody levels to common breast cancer proteins were quantified by enzyme-linked immunosorbent assay (ELISA). RT-PCR was performed on breast tissue samples to quantify immune-related gene expression levels between IN and IE. Bulk RNA sequencing was performed to identify differentially expressed genes and altered signaling pathways in the breasts of IN versus IE. In total, 188 patients were recruited (117 IN, 71 IE). Data demonstrated that IE patients had higher levels of antibodies to MUC-1, ER, and mammaglobin A compared to IN patients. MUC-1 expression was found to be higher in IE compared to IN breast tissue. RNA-seq analysis demonstrated upregulated pathways in IE breast tissue for B cell activation and development, Th2 related genes, T cell activation, chemotactic factors, and responses to estrogen. This is the first study to demonstrate that peri-implant inflammation extends beyond the implant capsule to breast parenchyma. Women with breast implants have more activated B cells in the breast parenchyma and elevated antibody responses to breast cancer antigen.

Wolbachia infection in Aedes aegypti does not affect its vectorial capacity for Dirofilaria immitis.

Mosquito-borne diseases such as dengue and filariasis are a growing public health concern in endemic countries. Biological approaches, such as the trans-infection of Wolbachia pipientis in mosquitoes, are an alternative vector control strategy, especially for arthropod-borne viruses such as dengue. In the present study, the effect of Wolbachia (wMel strain) on the vectorial capacity of Aedes aegypti for Dirofilaria immitis was studied. Our results showed that Wolbachia does not affect the phenotype of mosquito survival or the prevalence, number, and molting rate of third-stage larvae in both susceptible and resistant strains of Ae. aegypti. RNA-seq analysis of Malpighian tubules at 2days post-infection with D. immitis showed the differentially expressed genes (DEGs) with and without wMel infection. No characteristic immune-related gene expression patterns were observed among the DEGs. No significant change in the amount of Wolbachia was observed in the Ae. aegypti after D. immitis infection. Our results suggest that infection of D. immitis in Ae. aegypti populations will not interfere with Wolbachia-based vector control strategies in dengue-endemic areas where cases of D. immitis are present. This study demonstrated the veterinary medical validity of a dengue control program using Wolbachia.

Wnt/B-catenin activation and TP53 mutations associate with distinct immune profiles in advanced thyroid cancer.

Anaplastic thyroid carcinomas (ATCs) and poorly differentiated thyroid carcinomas (PDTCs) exhibit distinct immune-related gene expression profiles. Most ATCs are characterized by active immune interactions (hot or altered immunosuppressed immunophenotypes), while PDTCs are largely immunologically inert (cold immunophenotypes). This study aimed to elucidate the mechanisms driving these divergent immunological fates, focusing on the Wnt/β-catenin pathway and TP53 mutations. Our data reveal that ATCs frequently harbor TP53 mutations (83.3%), which correlate with a hot immunophenotype, characterized by high expression of β-catenin-regulated cytokine CCL4 and recruitment of CD103+ dendritic cells. Conversely, PDTCs, with a lower incidence of TP53 mutations (12.5%), often exhibit a cold immunophenotype. In cold cancers and PDTCs, β-catenin is overexpressed suggesting that Wnt/β-catenin pathway activation drives immune exclusion through CCL4 downregulation.Further analysis indicated that loss of p53 function is inversely correlated with β-catenin expression. P53-mutated cancers showed significantly higher expression of CCL4 and densities of CD103+ dendritic cells compared to their p53-wild-type counterparts. Additionally, p53-mutated ATCs expressed a higher number of immune-related genes, supporting the role of p53 loss in activating immune responses in cancer. Our study indicates a potential correlation between the activation of the Wnt/β-catenin pathway and the development of cold thyroid cancers, which may be mediated by the suppression of CCL4 expression. Concurrently, mutations in the p53 gene appear to be linked with the occurrence of hot thyroid cancers. While these associations are compelling, they are based on observational data. Experimental research is necessary to determine the causal relationships underlying these findings.

Galectin-9 activates host immune response and improve immunoprotection of Onychostoma macrolepis against Aeromonas hydrophila infection

Galectin-9 (Gal-9) belongs to a family of the glycan-binding proteins (GBPs) and is known to restrict bacterial activity via interacting with pathogen associated molecular pattern (PAMPs). However, the underlying immune mechanism of endogenous Gal-9 on fish against bacterial infection is still unclear. In this study, effect of Gal-9 from Onychostoma macrolepis (OmGal-9) on expression of immune related-genes were measured by HEK293T. The immune response of O. macrolepis with OmGal-9 overexpression to Aeromonas hydrophila (A. hydrophila) infection (1.65×108 CFU/mL) were evaluated by tissue bacterial load, fish survival rate and transcriptome analysis. The results showed that OmGal-9 displayed a punctate distribution in the nucleus and cytoplasm of HEK293T cells. Compared to cells transfected with the empty vector (EV) group, recombinant plasmid pEGFP-Gal9 treatment (Gal9) significantly down-regulated the expression of immune-related genes TNFα, STAT3, MyD88, LCK, and p52 of HEK293T cells stimulated with LPS at 24 h, while up-regulated IκBα and caspase1 (P < 0.05). The activities of catalase (CAT), superoxide dismutase (SOD), the total antioxidant capacity (T-AOC), alkaline phosphatase (AKP), acid phosphatase (ACP), and lysozyme (LZM) of O.macrolepis were significantly increased on 7 days in Gal9 group compared to EV group (P < 0.05). The bacterial load of liver, spleen, and kidney of O.macrolepis infected with A. hydrophila in Gal9 group at 24 h significantly lower than that in EV group (P < 0.05), and the survival rate has increased from 15% to 35%. A comparative transcriptome analysis between the Gal9 and EV group identified 305 differentially expressed genes (DEGs). The analysis showed that OmGal-9 might play important regulatory in glycolysis / gluconeogenesis, fatty acid degradation, and ascorbate and aldarate metabolism. Moreover, the immune-related DEGs were predominantly enriched in eleven pathways, with the most important three of them being linked to innate immunity: NOD-like, C-type lectin and Toll-like receptor signaling pathway. Taking together, OmGal-9 can enhance the resistance of fish to bacterial diseases by improving immune system function and activating immune-related pathways.

Sex-dependent differences in the ability of nicotine to modulate discrimination learning and cognitive flexibility in mice.

Nicotine, an addictive compound found in tobacco, functions as an agonist of nicotinic acetylcholine receptors (nAChRs) in the brain. Interestingly, nicotine has been reported to act as a cognitive enhancer in both human subjects and experimental animals. However, its effects in animal studies have not always been consistent, and sex differences have been identified in the effects of nicotine on several behaviors. Specifically, the role that sex plays in modulating the effects of nicotine on discrimination learning and cognitive flexibility in rodents is still unclear. Here, we evaluated sex-dependent differences in the effect of daily nicotine intraperitoneal (i.p.) administration at various doses (0.125, 0.25, and 0.5 mg/kg) on visual discrimination (VD) learning and reversal (VDR) learning in mice. In male mice, 0.5 mg/kg nicotine significantly improved performance in the VDR, but not the VD, task, while 0.5 mg/kg nicotine significantly worsened performance in the VD, but not VDR task in female mice. Furthermore, 0.25 mg/kg nicotine significantly worsened performance in the VD and VDR task only in female mice. Next, to investigate the cellular mechanisms that underlie the sex difference in the effects of nicotine on cognition, transcriptomic analyses were performed focusing on the medial prefrontal cortex tissue samples from male and female mice that had received continuous administration of nicotine for 3 or 18 days. As a result of pathway enrichment analysis and protein-protein interaction analysis using gene sets of differentially expressed genes, decreased expression of postsynaptic-related genes in males and increased expression of innate immunity-related genes in females were identified as possible molecular mechanisms related to sex differences in the effects of nicotine on cognition in discrimination learning and cognitive flexibility. Our result suggests that nicotine modulates cognitive function in a sex-dependent manner by alternating the expression of specific gene sets in the medial prefrontal cortex.