Immune Response Research Articles

Basophils: Regulators of lung inflammation over space and time.

In this issue of JEM, Schuijs et al. (https://doi.org/10.1084/jem.20240103) highlight a novel role for basophils during allergic immune responses to house dust mites (HDM). They reveal that interleukin-33 (IL-33)-activated basophils facilitate the recruitment and extravasation of Th2 cells into the lungs during a specific time frame via their interactions with pulmonary endothelial cells.

Environmental pollution by plasticizers and the relationship to vector dengue mosquito Aedes aegypti: Bisphenol A (BPA) affect the development and viral immune pathway response

Bisphenol A (BPA) is a widely used industrial chemical found in various products, leading to human exposure through dietary and non-dietary sources. It acts as an endocrine disruptor, affecting reproductive processes in vertebrates by binding to estrogen receptors. While its effects on vertebrates have been extensively studied, much less is known about its impact on invertebrates. This study investigates the effects of BPA on the development and immune response of Aedes aegypti mosquitoes, which are important vectors for arboviral diseases, such as dengue, an emergent viral disease worldwide. Artificial aquatic niches (AAN) were sampled, and BPA concentrations were quantified. Ae. aegypti larvae were exposed to varying BPA concentrations, and their development, fecundity, fertility, and immune response were assessed. Results show delayed development and decreased emergence of mosquitoes exposed to BPA. Females exposed to BPA exhibited reduced oviposition while hatching rates remained unaffected. Furthermore, BPA exposure altered the expression of immune response genes in adult mosquitoes, with differential effects observed between sexes. This suggests that BPA exposure during early developmental stages can modulate the antiviral immune response in adult mosquitoes, possibly through the 20-hydroxyecdysone (20E) signaling pathway. Overall, this study highlights the potential impact of BPA on the development and immune function of mosquito vectors, with implications for vector competence and disease transmission.

Effects of immune response on different nano-adjuvants combined with H11 antigen of Haemonchus contortus

The intestinal native protein H11 is one of the most immunodominant antigen of Haemonchus contortus. However, H11 combined with QuilA adjuvant shows only short-lived protection for animals. Nano-adjuvants have the huge potential to extend the immune response in human and animals. Here, we compared the immune responses induced by H11 combined with three nano-adjuvants including lipid nanoparticles (LNP), immunostimulating complex matrix (IMX) and AddaS03™. We measured the cytokine levels of goat PBMCs stimulated by H11 mixed with three nano-adjuvants and QuilA. Results showed that the transcriptions of IL-6, IL-8 and IFN-γ genes were significantly inhibited in all adjuvant group compared with PBS control. H11-IMX combination significantly up-regulated IL-2, IL-17 and TNF-α gene transcriptions. The H11-LNP group showed a significant increase in IL-17 and TNF-α transcriptions, while the H11-AddaS03™ group significantly increased IL-2 transcription. Additionally, mice immunized with these formulations were assessed for splenic lymphocyte proliferation. All H11-adjuvant combinations, except H11-LNP, significantly stimulated lymphocyte proliferation compared to the H11 alone and PBS control groups, with the H11-AddaS03™ combination showing the strongest effect. Analysis of serum antibody levels revealed that all immune groups induced high IgM levels, with H11-IMX inducing the highest IgG levels. Our results demonstrated that IMX or LNP combined with H11 mainly induced a Th17 cell immune response in goat PBMCs, while IMX or AddaS03™ combined with H11 could induce a strong humoral immune response in mice. This study elucidates the immune response profiles of different nano-adjuvant combined with H11 antigen, providing important insights for vaccine development against parasitic nematodes.

Carbohydrate Research Mini-review Relationships between bacteria and the mucus layer

The mucus layer on epithelial cells is an essential barrier, as well as a nutrient-rich niche for bacteria, forming a dynamic, functional and symbiotic ecosystem and first line of defense against invading pathogens. Particularly bacteria in biofilms are very difficult to eradicate. The extensively O-glycosylated mucins are the main glycoproteins in mucus that interact with microbes. For example, mucins act as adhesion receptors and nutritional substrates for gut bacteria. Mucins also play important roles in immune responses, and they control the composition of the microbiome, primarily due to the abundance of complex O-glycans. In inflammation or infection, the structures of mucin O-glycans can change and thus affect mucin function, impact biofilm formation and the induction of virulence pathways in bacteria. In turn, bacteria can support host cell growth, mucin production and can stimulate changes in the host immune system and responses leading to healthy tissue function. The external polysaccharides of bacteria are critical for controlling adhesion and biofilm formation. It is therefore important to understand the relationships between the mucus layer and microbes, the mechanisms and regulation of the biosynthesis of mucins, of bacterial surface polysaccharides, and adhesins. This knowledge can provide biomarkers, vaccines and help to develop new approaches for improved therapies, including antibiotic treatments.

Transcriptome-based characterization of 3’2’-cGAMP signaling mediated immune responses

Cyclic dinucleotides (CDNs) are critical adjuvants in antiviral vaccines and cancer immunotherapy, primarily through the activation of the cGAS-STING signaling pathway. Evaluating the immune responses triggered by CDNs is essential for the development of effective adjuvants. In this study, we performed a comparative transcriptome analysis to characterize the immune responses elicited by the recently identified nuclease-resistant Drosophila and bacterial CDN, 3’2’-cGAMP, in mammalian immune cells. We detected a robust induction of innate immune gene signature following 3’2’-cGAMP stimulation in digitonin-permeabilized mouse primary macrophages, comparable to the response observed with the canonical mammalian CDN, 2’3’-cGAMP. STING deficiency remarkably reduced 3’2’-cGAMP-induced phosphorylation of TBK1 and IRF3 and the induction of IFN-β, indicating that 3’2’-cGAMP signaling-mediated immune responses were mainly STING dependent. In comparison to 2’3’-cGAMP signaling, 3’2’-cGAMP signaling preferentially elicited many STING-dependent genes involved in transcription and nucleosome positioning and assembly in the nucleus, which are likely associated with several enriched pathways, including cellular senescence, HDACs deacetylate histones, and epigenetic regulation of gene expression. The integrative analysis further revealed that 3’2’-cGAMP signaling preferentially induced genes were associated with autoimmune disease-related processes, suggesting a potential side effect that requires monitoring when used as an adjuvant. In conclusion, this study provides the first transcriptional landscape of 3’2’-cGAMP signaling in mammals and reveals the immune response characteristics and potential side effects mediated by 3’2’-cGAMP signaling. These findings may aid in the development of 3’2’-cGAMP-based adjuvants for antiviral vaccines and cancer immunotherapy.

Ro 90-7501 suppresses colon cancer progression by inducing immunogenic cell death and promoting RIG-1-mediated autophagy.

Colon cancer is one of the leading causes of cancer-related mortality worldwide. Current treatments, including surgery, chemotherapy, and radiation therapy, often have limited efficacy due to tumor heterogeneity and resistance mechanisms. Therefore, there is a critical need for novel therapeutic strategies that can enhance the immune response against colon cancer cells while promoting their efficient clearance. In this study, we investigated the anti-tumor effects of Ro 90-7501, a specific small molecule, in colon cancer cell lines (HCT8 and SW480) and in vivo models. MTS, EdU, Scratch Wound and Transwell assays were performed to detect the cell proliferation and metastasis. Additionally, flow cytometry and immunofluorescence staining were used to analyze changes in apoptosis and necrosis. Furthermore, we examined its ability to induce immunogenic cell death (ICD) and promote retinoic acid-inducible gene I (RIG-I)-mediated autophagy. The expression levels of key molecules involved in ICD and autophagy were assessed using Western blot analysis, immunofluorescence staining, and enzyme-linked immunosorbent assay (ELISA). Our findings demonstrated that Ro 90-7501 significantly suppressed colon cancer cell proliferation and metastasis, inducing apoptosis and necrosis. Mechanistically, Ro 90-7501 triggered ICD by upregulating the exposure of calreticulin (CRT) on the cell surface and increasing the release of high mobility group box 1 (HMGB1) and extracellular ATP levels. Concurrently, it promoted RIG-I-mediated autophagy via the MAVS-TRAF6 signaling axis, evidenced by increased expression of autophagy-related genes, such as microtubule-associated protein 1 light chain 3 (LC3) and Beclin 1 proteins, coupled with a reduction in P62 protein. Additionally, Ro 90-7501 treatment activated the RIG-I-MAVS-TRAF6 signaling axis in colon cancer cells. Furthermore, Ro 90-7501 enhanced the secretion of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFα), thereby activating the immune response. In conclusion, Ro 90-7501 exhibits potent anti-tumor activity against colon cancer by inducing ICD and promoting RIG-I-mediated autophagy. These results suggest that Ro 90-7501 may serve as a promising therapeutic candidate for colon cancer treatment by enhancing both intrinsic cellular processes and adaptive immune responses. Further studies are warranted to elucidate the detailed mechanisms underlying these effects and to evaluate its therapeutic potential in clinical settings.

Comparative transcriptomic analysis revealed potential mechanisms regulating the hypertrophy of goose pectoral muscles

Pectoral muscle development is an important economic trait. According to the different essence, muscle development can be divided into 2 processes: embryonic muscle fiber generation and postnatal muscle fiber hypertrophy, and postnatal muscle fiber hypertrophy has a greater impact on muscle development than the number of muscle fibers formed during the embryonic phase in poultry. However, the underlying mechanisms regulating the hypertrophy of goose pectoral muscles have not been elucidated. Therefore, the purpose of the present study was to conduct transcriptome sequencing in pectoral muscles of both Landes (LD) and Sichuan White (SW) geese at 6, 10, and 30 weeks of age to reveal the molecular mechanisms regulating pectoral muscle hypertrophy through intra-breed and inter-breed bioinformatics analyses. Phenotypically, the pectoral muscle weight/index of LD and SW geese increased from 6 to 30 weeks of age, and except for the pectoral muscle index at 10 weeks of age (P = 0.962), at the same age, the pectoral muscle weight/index of LD geese were significantly higher than that of SW geese (P < 0.05). In transcriptional regulation, intra-breed bioinformatics analysis identified 3331 genes whose expression levels were opposite to the trend of pectoral muscle hypertrophy both in LD and SW geese, and the 3331 genes were mainly enriched into abundant KEGG pathways related to lipid metabolism, proliferation/apoptosis, and immune response. Moreover, 23 genes (including SLC2A10, TNFRSF1A, PRKAA1, SLC27A4, ITGB2, THY1, RHOA, MYL10, ACTB, PRKCB, PIK3R2, RAC2, DMD, LATS2, YAP1, WWTR1, SMAD7, CTGF, FGF1, AXIN2, GLI2, ID2, and CCND2) who were enriched in 6 crosstalk pathways named viral myocarditis, insulin resistance, sphingolipid signaling pathway, hippo signaling pathway, chemokine signaling pathway, and leukocyte transendothelial migration were identified as the key candidate genes regulating the hypertrophy of goose pectoral muscles. In inter-breed bioinformatics analysis, abundant different expression genes (DEGs) related to lipid metabolism, immune response, and proliferation/apoptosis were identified between LD and SW geese too, and compared with SW geese, the expression level of MYL10 in LD geese was lower, while the expression levels of GLI2/CTGF/SMAD7 in LD geese were higher. These results suggested that the hypertrophy of goose pectoral muscles might be achieved through more lipid deposition and less leukocyte infiltration to promote the proliferation of cells within the muscles, and the low expression of MYL10 and high expressions of GLI2/CTGF/SMAD7 might the keys to induce the pectoral muscle hypertrophy of LD geese from 6 to 30 weeks of age over that of SW geese. All data the present study obtained will provide new insights into the molecular mechanisms regulating the hypertrophy of goose pectoral muscles.

Safety and immunogenicity of the yellow fever vaccine for patients with end-stage renal disease.

In December 2016, an outbreak of sylvatic yellow fever (YF) occurred in the non-endemic areas of the south-eastern region of Brazil. The immune response to the yellow fever vaccine and its safety in individuals with chronic kidney disease (CKD) living in YF-endemic regions are not thoroughly understood. The objective of this study is to assess the incidence of adverse events and the serological response after primary vaccination with the 17DD-YF vaccine in CKD patients undergoing dialysis. This was a multicenter, retrospective cohort study involving 223 individuals with CKD who were on dialysis after primary vaccination against YF. Clinical and epidemiologic characteristics were collected and the vaccine adverse event (VAE) were assessed. Around 35 months after vaccination, the serological response was evaluated in 71 (32%) patients using neutralization tests. No serious VAE occurred in any patient. Local reactions were reported in 13 individuals (5.8%), while 6 (2.7%) reported generalized systemic reactions and 205 (91.9%) did not display any VAE. No clinical or epidemiologic characteristic predicted the occurrence of VAE. Adequate serological response was found in 38% of participants and none of the clinical or epidemiological characteristics were associated with immunogenicity. The outcomes of our study suggest that the yellow YF vaccine is well-tolerated in CKD patients undergoing dialysis, but it does not induce adequate immune response. Future research should focus on evaluating both cellular and humoral immune responses following administration of various doses of the YF vaccine.

Bacillus subtilis supplementation enhances the growth performance, immune indicators, and stability of the intestinal flora of Cherax quadricarinatus

The addition of Bacillus subtilis to the diet can enhance the natural defenses of aquatic creatures and improve their ability to combat diseases. We conducted a study to assess the effects of different concentrations (1.5×106 CFU/g, 1.5×107 CFU/g, and 1.5×108 CFU/g) of B. subtilis on the growth, development, immune response, and gut microbiota of Cherax quadricarinatus over a 45-day period. The highest final weight and growth rate were observed in the group that received 1.5×106 CFU/g of B. subtilis. Furthermore, enzyme activities—including α-amylase, trypsin, alanine aminotransferase, aspartate aminotransferase, and superoxide dismutase (SOD)—were higher in the groups supplemented with B. subtilis compared to those in the control group. Analysis of the gut microbiome through metagenomic sequencing showed consistent levels of α-Proteobacteria but varying levels of Bacteroidetes, Firmicutes, and Actinobacteria. Aeromonas was inhibited during the early stages of culture, leading to enhanced resistance to infection in crayfish that received B. subtilis supplementation. Subsequent infection tests with Aeromonas versonii revealed significantly higher enzyme activities (alkaline phosphatase, acid phosphatase, and SOD) in the experimental groups. The expression of antilipopolysaccharide factor (ALF) and SOD was also notably higher in the experimental groups. Overall, supplementing with B. subtilis showed beneficial effects on the immune response and gut microbiota composition in red claw crayfish.

FTIR monitoring of the 13-valent pneumococcal conjugate vaccine for lung cancer patients: Changes in amides vibrations correlated with biochemical assays

Lung cancer is one of the most lethal cancers. Unfortunately, respiratory tract infections are very common in lung cancer patients, delaying appropriate anticancer therapy. To increase therapy efficiency, in this study we examined the effect of 13-Valent Pneumococcal Conjugate Vaccine on the immune response in lung cancer patients, which indirectly affects the success of anticancer therapy. The study was done using biochemical tests and Fourier Transform InfraRed (FTIR) spectroscopy. For this purpose, serum from lung cancer patients aged 52 ± 9 years (III and IV clinical stage; 79 %; n = 103) before and seven as well as 30 days after vaccination was collected. Obtained results showed increasing concentrations of immunoglobulin IgG and IgG2 groups in patients after vaccination in comparison with group before vaccination. This result was confirmed by FTIR spectroscopy, where higher absorbances of amides vibrations were observed after vaccination. Interestingly, lack of differences in the amides absorbances between patients 7 and 30 days after vaccination were noticed. FTIR spectra also showed changes in the ratio between amide I and amide III as well as between amide II and amide III in the groups of patients after vaccination. From deconvolution of made I range (1600 cm−1–1700 cm−1) decrease of the ratio between α-helix and β-sheet around 0.05 was noticed in serum collected from patients after vaccination in comparison with patients before vaccination. Using Principal Component Analysis (PCA) analysis of FTIR data it was observed that serum collected from all three analyzed groups of samples was possible to differentiate. The highest accuracy in differentiation group of samples before and 7 days after vaccination was visible in amide I, while before and 30 days after vaccination using amide II. Correlation between immunoglobulin IgG and IgG2 concentrations obtained by biochemical assays and FTIR were noticed only in the group of serum collected 30 days after vaccination, which suggested that FTIR spectroscopy reflects biochemical data.

Physiological plasticity and life history traits affect Chamelea gallina acclimatory responses during a marine heatwave.

The striped venus clam (Chamelea gallina) is a relevant economic resource in the Adriatic Sea. This study explored the physiological status of C. gallina at four sites selected along a gradient from high to low incidence of recorded historical mortality events and low to high productivity in the Northwestern Adriatic Sea. Investigations were performed during the marine heatwave in 2022 (from July to November). The optimal temperature range for C. gallina was exceeded in July and September, exacerbating stress conditions and a poor nutritional status, particularly at the low productivity sites. Transcriptional profiles assessed in digestive glands showed that clams from the low productivity sites up-regulated transcripts related to feeding/digestive functions as a possible compensatory mechanism to withstand adverse environmental conditions. Clams from the high productivity sites, that in a previous study showed enrichment of health-promoting microbiome components, displayed a healthier metabolic makeup (IDH up-regulation) and induction of protective antioxidant and immune responses. These features are hallmarks of putative enhanced resilience of the species towards environmental stress. Despite the well-known high sensitivity of C. gallina to environmental variations and its narrow window of acclimatory potential, results highlight that local conditions may influence physiological plasticity of this clam species and shape either positively or negatively its response capabilities to environmental changes. The identification of health-promoting endogenous mechanisms both from the animal (this study) and from its associated microbiome may provide the foundation for developing novel tools and strategies to improve clam health and production in low productivity areas or under adverse environmental conditions.

Characterization of an RR-2 cuticle protein DcCP8 and its potential application based on SPc nanoparticle-wrapped dsRNA in Diaphorina citri.

The insect cuticle consists of chitin fibers and a protein matrix, which plays an important role in protecting the body from invasion of various pathogens and prevents water loss. Periodic synthesis and degradation of the cuticle is required for the growth and development of insects. Key genes involved in cuticle formation have long been considered a potential target for pest control. In this study, a member of the RR-2 subfamily of cuticular protein 8 (DcCP8) was identified from the Diaphorina citri genome database. Immunofluorescence analysis suggested that DcCP8 was mainly located in the Diaphorina citri exocuticle and can be induced to up-regulate 12 h following 20-hydroxyecdysone (20E) treatment. Silencing of DcCP8 by RNA interference (RNAi) significantly disrupted the metamorphosis to the adult stage, and improved the permeability of the cuticle. Transmission electron microscopy (TEM) analysis revealed that the synthesis of the exocuticle was impressed after silencing of DcCP8. Furthermore, the recombinant DcCP8 protein exhibited chitin-binding properties in vitro, down-regulation of DcCP8 significantly inhibited expression levels of chitin metabolism-related genes. Additionally, a sprayable RNAi method targeting DcCP8 based on star polycation (SPc) nanoparticles-wrapped double-stranded RNA (dsRNA) significantly increased Diaphorina citri mortality. Transcriptome sequencing further confirmed that genes associated with the endocytic pathway and immune response were up-regulated in Diaphorina citri after SPc treatment. The current study indicated that DcCP8 is critical for the formation of Diaphorina citri exocuticles, and lays a foundation for Diaphorina citri control based on large-scale dsRNA nanoparticles. © 2024 Society of Chemical Industry.

Deletion of the phd3 in zebrafish results in increased resistance to Aeromonas hydrophila infection

Aeromonas hydrophila, a gram-negative pathogen prevalent in aquatic environments, is a known inducer of septicemia in aquatic animals, causing considerable losses in aquaculture. The limited effectiveness of conventional drug therapies underscores the need for exploring innovative treatment strategies. Gene knockout technology presents a promising approach for exploring the immune response in zebrafish and developing therapeutic interventions for aquatic organisms diseases. This study focuses on elucidating the mechanism of action of phd3 in zebrafish against Aeromonas hydrophila through the creation of a phd3 knockout model. Our findings reveal a high degree of conservation of phd3 sequences between zebrafish and commercially important fish species, making it a suitable model organism for studying fish inflammation. Knocking out phd3 significantly improved the resistance of zebrafish to Aeromonas hydrophila, reduced tissue damage, increased survival rates, and decreased bacterial burden. Furthermore, the downregulation of phd3 enhanced immune responses, antioxidant levels, endoplasmic reticulum stress, autophagy reactions and apoptosis. This research underscores the crucial role of phd3 in zebrafish innate immunity, offering novel insights into the prevention and management of diseases in aquatic organisms, and potential immunotherapeutic strategies. Our findings have significant implications for the future development of targeted therapeutic strategies against Aeromonas hydrophila and other aquatic pathogens.

Modulation of Connexin 43 in Viral Infections

Connexins are essential for intercellular communication through gap junctions and the maintenance of cellular and tissue homeostasis. Connexin 43 (Cx43) is the most ubiquitously expressed connexin. As well as regulating homeostasis, Cx43 hemichannels and gap junctions play important roles in inflammation and the immune response. This, coupled with a range of non-channel functions performed by Cx43 makes it an attractive target for viruses. Recently, several groups have begun to explore the relationship between Cx43 and viral infection, with a diverse array of viruses being found to alter Cx43 hemichannels/gap junctions. Importantly, this includes several small DNA tumour viruses, which may target Cx43 to promote tumorigenesis. This review focuses on the ability of selected RNA and DNA viruses to either positively or negatively regulate Cx43 hemichannels and gap junctions in order to carry out their lifecycles. The role of Cx43 regulation by tumour viruses is also discussed in relation to tumour progression.

Effects of dietary mangosteen peel powder and extract on the growth performance, meat quality and indicators for immunity, gut health and antioxidant activity in broiler chicks

The objective of this study was to evaluate the effects of dietary mangosteen peel preparations, either powdered (MspP) or ethanolic extract (MspE), on the growth performance, meat quality, immune response, gut health, serum biochemical profiles, and antioxidant activity of broiler chicks. A total of 480 day-old straight-run broiler chicks (Ross 308) were randomly placed into four treatments, with eight replicates of 12 chicks each, and subjected to one of the four experimental diets for 21 days. The corn and soybean meal-based diet was supplemented with 2% MspP (20 g per kg of diet) or 0.05% and 0.1% MspE (0.5 g and 1.0 g per kg of diet). Data were analyzed using analysis of variance, and post hoc comparisons of treatments were performed using Tukey's Honestly Significant Difference test. From days 0 to 21, dietary mangosteen peel preparations did not affect growth performance (body weight gain, feed intake, and feed conversion ratio), thigh meat and tibia characteristics, serum markers of innate immunity (interferon-r, interleukin-10, alpha-1-acid glycoprotein, and nitric oxide), and ileal morphology in broiler chicks (P > 0.05). Dietary mangosteen peel preparations increased the percentage of high-density lipoprotein cholesterol and decreased the relative concentrations of isobutyrate and branched-chain fatty acids in the cecal digesta compared with the control chickens. Notably, dietary mangosteen peel preparations altered the antioxidant characteristics of the serum, liver, and thigh meat. Dietary MspE increased glutathione peroxidase (P = 0.039) and catalase (P = 0.008) in the serum and catalase in the liver (P = 0.05) and thigh meat (P = 0.01) compared to the control group. In addition, dietary MspP increased catalase levels in thigh meat compared to those in the control diet-fed chickens (P = 0.01). The concentration of malondialdehyde, an indicator of lipid peroxidation, was lower in all chicks-fed diets containing mangosteen peel preparations; however, statistical significance was only noted in the serum samples (P < 0.0001). Collectively, our study shows that dietary mangosteen peel preparations are potent natural antioxidants that can be used as functional dietary additives to effectively mitigate oxidative stress in broiler chicks.

Simulated microgravity environment inhibits matrix mineralization during the osteoblast to osteocyte differentiation

This study investigates the effects of microgravity on the differentiation and mineralization of IDG-SW3 osteocyte-like cells to understand the response of bone cells to microgravity and develop strategies to mitigate bone loss in astronauts. IDG-SW3 cells were cultured in collagen-coated dishes and subjected to a 3D clinostat to simulate microgravity 14 days after initiating differentiation. The static group remained under normal gravity. Cells were analyzed on days 14, 18, 22, and 26. Alizarin red staining demonstrated a substantial and time-dependent increase in mineralization in the static group, whereas the microgravity group exhibited little detectable mineralization throughout the experimental period. Quantitative RT-PCR revealed significant upregulation of Rankl, Alpl, Dmp1, and Fgf23 and downregulation of Sost and Phex in the microgravity group. RNA sequencing on day 26 showed distinct gene expression profiles between conditions. Heatmaps highlighted upregulated genes (Ptgs2, Alpl, Comp, Atf4, Lox) and downregulated genes (Rspo2, Ank, Ptn, Mmp13, Aspn, Spp1) under microgravity. Gene ontology (GO) enrichment analysis indicated that upregulated genes were associated with cytoskeletal organization and receptor activities, while downregulated genes were linked to extracellular matrix components and immune response. These findings provide insights into the molecular mechanisms of bone loss in space and emphasize the importance of gravity in bone remodeling. Future studies should validate these genes' functions in osteocyte biology under microgravity.

Proteomic signatures of ambient air pollution and risk of non-alcoholic fatty liver disease: A prospective cohort study in the UK Biobank.

Air pollution has been linked with non-alcoholic fatty liver disease (NAFLD), but the underlying mechanisms characterized by perturbations in the circulating proteome profile are largely unknown. Therefore, we included 51,357 participants from the UK Biobank with 2941 plasma proteins measured in blood samples collected between 2006 and 2010, measurements of annual fine particular matter <2.5 μm in diameter (PM2.5) and nitrogen dioxide (NO2), and follow-up data on NAFLD (743 incident cases occurred over a median follow-up of 13.6 years). Multiple linear regression was used to identify proteins associated with PM2.5 and NO2. Cox proportional hazards models were applied to assess associations of PM2.5 and NO2 and identified proteins with incident NAFLD. Mediation analyses were conducted to explore the mediation role of proteins in the associations between air pollution and incident NAFLD. After adjusting for selected covariates, PM2.5 (hazard ratio [HR] = 2.57, 95%CI:1.27, 5.21, per ln increase) and NO2 (HR = 1.43, 95%CI: 1.10, 1.84, per ln increase) were positively associated with incident NAFLD. We identified 138 proteins associated with PM2.5 (92 positively, 46 inversely, FDR <0.05) and 143 with NO2 (100 positively, 43 inversely). Of the proteins that were significantly associated with both PM2.5 and NO2, 93 (79 positively, 14 inversely) and 79 (69 positively, 10 inversely) were significantly associated with incident NAFLD. Furthermore, 84 PM2.5-associated proteins and 66 NO2-associated proteins significantly mediated the corresponding association between air pollutants and incident NAFLD, with the proportion of mediation effects ranging from 3.2 % to 27.3 % for PM2.5 and 2.6 % to 20.8 % for NO2, respectively. Of note, the majority of significant mediating proteins were enriched in pathways of cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptor. Our findings suggested that long-term exposure to PM2.5 and NO2 was associated with an increased risk of NAFLD partially by perturbating circulating proteins involved in pathways of inflammation and immunity responses.

The Association between NADPH Oxidase 2 (NOX2) and Drug Resistance in Cancer.

NADPH oxidase, as a major source of intracellular reactive oxygen species (ROS), assumes an important role in the immune response and oxidative stress response of the body. NADPH oxidase 2 (NOX2) is the first and most representative member of the NADPH oxidase family, and its effects on the development of tumor cells are gaining more and more attention. Our previous study suggested that NCF4 polymorphism in p40phox, a key subunit of NOX2, affected the outcome of diffuse large B-cell lymphoma patients treated with rituximab. It hypothesized that NOX2-mediated ROS could enhance the cytotoxic effects of some anti-tumor drugs in favor of patients with tumors. Several reviews have summarized the role of NOX2 and its congeners-mediated ROS in anti-tumor therapy, but few studies focused on the relationship between the expression of NOX2 and anti-tumor drug resistance. In this article, we systematically introduced the NOX family, represented by NOX2, and a classification of the latest inhibitors and agonists of NOX2. It will help researchers to have a more rational and objective understanding of the dual role of NOX2 in tumor drug resistance and is expected to provide new ideas for oncology treatment and overcoming drug resistance in cancer.

Genome-wide identification of gap junction gene family and their expression profiles under low temperature stress in noble scallop Chlamys nobilis

Gap junctions, formed by gap junction proteins (GJ), play crucial roles in cell signaling and immune responses. The structure and function of the GJ from vertebrates (called connexins) have been extensively studied. However, little is known about the proteins forming gap junctions in invertebrates (called innexins). In this study, 14 GJ genes of Chlamys nobilis were identified. GJ proteins are mainly distributed on the plasma membrane, and all proteins are hydrophilic Phylogenetic tree analysis showed that the GJ proteins in C. nobilis were distantly related to those in vertebrates but closely related to those in invertebrates. Conserved motifs analysis of these GJ proteins in C. nobilis identified to have 10 conserved motifs, similar to gap junction proteins in other bivalves. Moreover, expression profiles of CnGJ genes under chronic and acute low temperature stress were also investigated. Results showed that chronic low temperature stress had a significant effect on the expression levels of CnGJ genes, and the expression profiles of CnGJ genes showed significantly variation under acute low temperature stress. All these results indicated that CnGJ genes play important roles in environmental adaptation in scallops. The present study initially elucidated the function of gap junction genes in noble scallop C. nobilis, which provides new insights into the GJ genes in mollusks and will help us better understand their roles in environmental stress in scallops.

Sophoricoside reduces inflammation in type II collagen-induced arthritis by downregulating NLRP3 signaling

Immune responses, especially NLRP3 signaling in macrophages, play critical roles in rheumatoid arthritis (RA), an autoimmune and inflammatory disease. In this study, we aimed to identify novel therapies for RA. We focused on sophoricoside (SOP), an isoflavone glycoside isolated from Sophora japonica. We predicted the targets of SOP and performed a Gene Ontology analysis to assess its effects. The results suggested that SOP is related to inflammation regulation. We verified these findings by performing in vitro experiments with M1 macrophages differentiated from human peripheral blood monocytes (THP-1 cells). Sophoricoside administration reduced inflammatory activity and NLRP3, Caspase-1, and IL-1β protein levels in macrophages. In addition, SOP and triptolide (TP) was administered intragastrically to male SD rats (n = 40) in a collagen-induced arthritis model. We observed that SOP and TP reduced the inflammatory responses and symptoms of RA. Moreover, unlike TP, SOP showed no liver or kidney toxicity in rats. In conclusion, SOP reduces inflammation in type II collagen-induced arthritis by downregulating NLRP3 signaling and has potential for future clinical applications as an ideal therapy for RA.