Immune Stress Research Articles

Impact of maternal protein restriction on the proteomic landscape of male rat lungs across the lifespan

The developmental origins of healthy and disease (DOHaD) concept has demonstrated a higher rate of chronic diseases in the adult population of individuals whose mothers experienced severe maternal protein restriction (MPR). Using proteomic and in silico analyses, we investigated the lung proteomic profile of young and aged rats exposed to MPR during pregnancy and lactation. Our results demonstrated that MPR lead to structural and immune system pathways changes, and this outcome is coupled with a rise in the PI3k-AKT-mTOR signaling pathway, with increased MMP-2 activity, and CD8 expression in the early life, with long-term effects with aging. This led to the identification of commonly or inversely differentially expressed targets in early life and aging, revealing dysregulated pathways related to the immune system, stress, muscle contraction, tight junctions, and hemostasis. We identified three miRNAs (miR-378a-3p, miR-378a-5p, let-7a-5p) that regulate four proteins (ACTN4, PPIA, HSPA5, CALM1) as probable epigenetic lung marks generated by MPR. In conclusion, MPR impacts the lungs early in life, increasing the possibility of long-lasting negative outcomes for respiratory disorders in the offspring.

Transcriptome analysis reveals high concentration of resveratrol promotes lipid synthesis and induces apoptosis in Siberian sturgeon (Acipenser baerii)

Resveratrol has been reported to promote immunity and decrease oxidative stress, but which demonstrates biphasic effects relied on the use concentration. In this study, the effects of diet supplement with a relative high concentration of resveratrol (0.32 mg/kg) on metabolism, antioxidation and apoptosis of liver were investigated in Siberian sturgeon. The results showed that resveratrol significantly increased the lipid synthesis and the apoptosis, but did not either activate the antioxidant NRF2/KEAP1 pathway or enhance the antioxidant enzyme activity. Transcriptome analysis revealed significant changes in regulatory pathways related to glycolipid, including PPAR signaling pathway, Insulin signaling pathway, Fatty acid biosynthesis, and Glycolysis/Gluconeogenesis. In addition, resveratrol significantly increased the lipid synthesis genes (accα and fas), fatty acid transport gene (fatp 6) and gluconeogenesis gene (gck), but decreased the survival-promoting genes (gadd45β and igf 1). These findings highlight a significant effect of resveratrol on glycolipid metabolism in Siberian sturgeon. Moreover, this study also demonstrated that 0.32 mg/kg resveratrol has physiological toxicity to the liver of Siberian sturgeon, indicating that this dose is too high for Siberian sturgeon. Thus, our study provides a valuable insight for future research and application of resveratrol in fish.

Potential adaptation of scleractinian coral Pocillopora damicornis during hypo-salinity stress caused by extreme pre-flood rainfall over south China

Global warming intensifies the water cycle, resulting in significant increases in precipitation and river runoff, which brings severe hypo-salinity stress to nearshore coral reefs. Ecological investigations have found that some corals exhibit remarkable adaptability to hypo-salinity stress during mass-bleaching events. However, the exact cause of this phenomenon remains unclear. To elucidate the potential molecular mechanism leading to high tolerance to hypo-salinity stress, Pocillopora damicornis was used as a research object in this study. We compared the differences in transcriptional responses and symbiotic microbiomes between bleaching and unbleaching P. damicornis during hypo-salinity stress caused by extreme pre-flood rainfall over South China in 2022. The results showed that: (1) Under hypo-salinity stress, the coral genes related to immune defense and cellular stress were significantly upregulated in bleaching corals, indicating more severe immune damage and stress, and the Symbiodiniaceae had no significant gene enrichment. Conversely, metabolic genes related to glycolysis/gluconeogenesis were significantly downregulated in unbleaching corals, whereas Symbiodiniaceae genes related to oxidative phosphorylation were significantly upregulated to meet the energy requirements of coral holobiont; (2) C1d was the dominant Symbiodiniaceae subclade in all samples, with no significant difference between the two groups; (3) The symbiotic bacterial community structure was reorganized under hypo-salinity stress. The abundance of opportunistic bacteria increased significantly in bleaching coral, whereas the relative abundance of probiotics was higher in unbleaching coral. This may be due to severe immune damage, making the coral more susceptible to opportunistic infection and bleaching. These results suggest that long-term hypo-salinity acclimation in the Pearl River Estuary enhances the tolerance of some corals to hypo-salinity stress. Corals with higher tolerance may reduce energy consumption by slowing down their metabolism, improve the energy metabolism of Symbiodiniaceae to meet the energy requirements of the coral holobiont, and alter the structure of symbiotic bacterial communities to avoid bleaching.

Impact of minimally invasive surgery on immune function and stress response in gastric cancer patients.

Gastric cancer remains a leading cause of cancer-related mortality globally. Traditional open surgery for gastric cancer is often associated with significant morbidity and prolonged recovery. To evaluate the effectiveness of laparoscopic minimally invasive surgery as an alternative to traditional open surgery for gastric cancer, focusing on its potential to reduce trauma, accelerate recovery, and achieve comparable oncological outcomes. This study retrospectively analyzed 203 patients with gastric cancer who underwent surgery at the Shanghai Health Medical College Affiliated Chongming Hospital from January 2020 to December 2023. The patients were divided into two groups: Minimally invasive surgery group (n = 102), who underwent laparoscopic gastrectomy, and open surgery group (n = 101), who underwent traditional open gastrectomy. We compared surgical indicators (surgical incision size, intraoperative blood loss, surgical duration, and number of lymph nodes dissected), recovery parameters (time to first flatus, time to start eating, time to ambulation, and length of hospital stay), immune function (levels of IgA, IgG, and IgM), intestinal barrier function (levels of D-lactic acid and diamine oxidase), and stress response (levels of C-reactive protein, interleukin-6, and procalcitonin). The minimally invasive surgery group demonstrated significantly better outcomes in terms of surgical indicators, including smaller incisions, less blood loss, shorter surgery time, and more lymph nodes dissected (P < 0.05 for all). Recovery was also faster in the minimally invasive surgery group, with earlier return of bowel function, earlier initiation of diet, quicker mobilization, and shorter hospital stays (P < 0.05 for all). Furthermore, patients in the minimally invasive surgery group had better preserved immune function, superior intestinal barrier function, and a less pronounced stress response postoperatively (P < 0.05 for all). Laparoscopic minimally invasive surgery for gastric cancer not only provides superior surgical indicators and faster recovery but also offers advantages in preserving immune function, protecting intestinal barrier function, and mitigating the stress response compared to traditional open surgery. These findings support the broader adoption of laparoscopic techniques in the management of gastric cancer.

Sulforaphane modulates some stress parameters in TPT-exposed Cyprinus carpio in relation to liver metabolome

This study aimed to investigate the protective effect of sulforaphane (SFN) on liver injury induced by triphenyltin (TPT) in Cyprinus carpio (C. carpio). The fish (average weight of 56.9±0.4 g) were divided into 4 groups with four replicates: the control, TPT, SFN+TPT and SFN groups. Twenty fish were selected from each tank and cultured for 8 weeks. Then, serum and liver samples were collected for physiological, biochemical and metabolomic analyses. In the present study, TPT downregulated the expression of the lysozyme gene, upregulated HSP70 and Hsp90 gene expression, and decreased the activities of serum antioxidant enzymes (SOD, CAT, and GPX). However, dietary SFN alleviated oxidative stress, and prevented changes in immune genes. Metabolomic analysis revealed that TPT exposure changed key metabolites in the main phenylalanine, fatty acid and glycerophosphatide metabolic pathways, which are related to inflammation, oxidative stress and immunity and might also lead to an imbalance of liver energy and lipid metabolism. Dietary SFN promoted amino acid metabolism and increased metabolites related to immunity, anti-inflammation, antioxidation, and protein synthesis in liver of C. carpio. In summary, dietary SFN supplementation reversed TPT-induced decreases in immunity and oxidative stress and regulated amino acid metabolism, lipid metabolism, inflammation and immunity-related metabolic pathways.

Dragon fruit-derived oligosaccharides alter hemocyte-mediated immunity and expression of genes related to innate immunity and oxidative stress in Daphnia magna

Dragon fruit oligosaccharide (DFO) is an indigestible prebiotic that enhances the growth and reproduction of Daphnia magna, increases the expression of genes involved in immunity, and reduces oxidative stress. This study investigated the effects of DFO on the expression of innate immunity- (Toll, Pelle, proPO, A2M, and CTL), oxidative stress- (Mn-SOD), and nitric oxide (NO) synthesis-related genes (NOS1, NOS2, and arginase) as well as NO localization and number of hemocytes in D. magna. For this ten-day-old D. magna were treated with 0 or 9 mg l−1 of DFO for 24 and 85 h. Gene expression levels, NO intensity and localization, and total hemocytes were evaluated. After 24 h, the expression of Toll and proPO increased significantly (p < 0.05), while that of C-type lectins (CTL) was reduced (p < 0.05). At 85 h, Mn-SOD and CTL expressions were markedly suppressed (p < 0.05). NO was mostly localized in the foregut, midgut, hindgut, and carapace. The expression of NOS1 was reduced after 24 h (p < 0.05). In addition, NO intensity at 24 h was insignificantly lower than the control (p > 0.05). At 85 h, the expression of NOS1, NOS2, and arginase was higher than control, but NO intensity did not differ significantly (p > 0.05). Furthermore, the total hemocyte count elevated remarkably at 85 h (p < 0.05). Our study suggested that 9 mg l−1 of DFO could alter the expression of the genes related to innate immunity, oxidative stress, and NO synthesis in D. magna and significantly stimulate hemocyte production.

The Role of Inositols in Endocrine and Neuroendocrine Tumors.

Inositols have demonstrated a role in cancer prevention and treatment in many kinds of neoplasms. Their molecular mechanisms vary from the regulation of survival and proliferative pathways to the modulation of immunity and oxidative stress. The dysregulation of many pathways and mechanisms regulated by inositols has been demonstrated in endocrine and neuroendocrine tumors but the role of inositol supplementation in this context has not been clarified. The aim of this review is to summarize the molecular basis of the possible role of inositols in endocrine and neuroendocrine tumors, proposing it as an adjuvant therapy.

Tris(1-chloro-2-propyl) phosphate enhances the adverse effects of biodegradable polylactic acid microplastics on the mussel Mytilus coruscus

Microplastics (MPs) and organophosphate flame retardants (OPFRs) have recently become ubiquitous and cumulative pollutants in the oceans. Since OPFRs are added to or adsorbed onto MPs as additives, it is necessary to study the composite contamination of OPFRs and MPs, with less focus on bio-based PLA. Therefore, this study focused on the ecotoxicity of the biodegradable MP polylactic acid (PLA) (5 μm, irregular fragments, 102 and 106 particles/L), and a representative OPFRs tris(1-chloro-2-propyl) phosphate (TCPP, 0.5 and 50 μg/L) at environmental and high concentrations. The mussel Mytilus coruscus was used as a standardised bioindicator for exposure experiments. The focus was on examining oxidative stress (catalase, CAT, superoxide dismutase, SOD, malondialdehyde, MDA), immune responses acid (phosphatase, ACP, alkaline phosphatase, AKP, lysozyme, LZM), neurotoxicity (acetylcholinesterase, AChE), energy metabolism (lactate dehydrogenase, LDH, succinate dehydrogenase, SDH, hexokinase, HK), and physiological indices (absorption efficiency, AE, excretion rate, ER, respiration rate, RR, condition index, CI) after 14 days exposure. The results of significantly increased oxidative stress and immune responses, and significantly disturbed energy metabolism and physiological activities, together with an integrated biomarker response (IBR) analysis, indicate that bio-based PLA MPs and TCPP could cause adverse effects on mussels. Meanwhile, TCPP interacted significantly with PLA, especially at environmental concentrations, resulting in more severe negative impacts on oxidative and immune stress, and neurotoxicity. The more severe adverse effects at environmental concentrations indicate higher ecological risks of PLA, TCPP and their combination in the real marine environment. Our study presents reliable data on the complex effects of bio-based MP PLA, TCPP and their combination on marine organisms and the environment.

Effects of spinal-epidural anesthesia combined with intravenous etomidate on adrenocortical and immune stress in elderly patients undergoing anorectal surgery: A retrospective analysis.

The management of anesthesia in elderly patients undergoing surgery presents unique challenges, particularly in mitigating stress responses and ensuring stability. Etomidate may alleviate adrenocortical and immune stress. This study aims to investigate the anesthetic effects of combined spinal-epidural anesthesia (CSEA) supplemented with etomidate during anorectal surgery in elderly patients. The medical records of 49 cases treated with CSEA and etomidate (ETO group) and 48 cases treated with CSEA alone (control group) were reviewed and analyzed. All patients received ropivacaine hydrochloride for anesthesia, with the ETO group additionally receiving an infusion of etomidate for sedation. Parameters such as arterial blood gas, visual analog scale (VAS), Ramsay sedation scale (RSS), serum cortisol and norepinephrine levels, pro-inflammatory cytokines, and lymphocyte ratios were assessed at different time points. Compared to the control group, the ETO group showed increased mean arterial pressure, decreased heart rate, and elevated arterial SpO2 30 minutes after anesthesia. The ETO group also had higher RSS scores, lower VAS scores, and reduced serum cortisol and norepinephrine levels. Additionally, decreased levels of pro-inflammatory cytokines, such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-8, were observed, along with an increase in the regulatory cytokine IL-10. An increased proportion of CD4+ T cells and a higher CD4/CD8 ratio were also noted. This study demonstrates the benefits of using etomidate to mitigate adrenocortical and immune stress in elderly patients undergoing anorectal surgery.

Abstract Or108: The role of SARM1 in regulation of immune response in heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is an unmet medical need. Recent studies have shown that HFpEF is associated with immune dysregulation and decline in nicotinamide adenine dinucleotide (NAD + ) levels. However, the molecular mechanisms linking these factors in HFpEF are not completely understood. Sterile alpha and TIR motif-containing 1 (SARM1) is a NAD + consuming enzyme that may regulate immune response and NAD + metabolism. Here, we investigated the role of SARM1 in HFpEF pathophysiology. We utilized a two-hit diet model to induce HFpEF in mice (HFpEF diet: high-fat diet and L-NAME). Wild-type (WT) mice on HFpEF diet showed progressive decline in diastolic function (e.g. decreased E’/A’, increased relaxation time, IVRT) at 5- and 15-week, associated with unchanged systolic function and increased cardiac hypertrophy. Despite decline in NAD + levels as previously reported in HFpEF hearts, qPCR analysis showed no significant differences in the expression of enzymes involved in NAD + biosynthesis including the salvage, Preiss-Handler and de novo pathways. We employed RNA-sequencing to identify cardiac gene signatures that are associated with HFpEF. Gene ontology analysis showed activation of various immune pathways in HFpEF hearts. Using flow cytometry analysis, we observed around 66% increase in total leukocytes (CD45+) number, along with infiltration of both T cells (CD3+ CD4+/CD8+) and myeloid cell populations (CD11b+) in HFpEF hearts. To understand the role of SARM1 in HFpEF pathogenesis, we subjected global SARM1 knock out (KO) mice to HFpEF diet. SARM1 KO hearts had improved diastolic function and reduced hypertrophy after 15-week HFpEF diet. RNA-sequencing of SARM1 KO-HFpEF hearts showed downregulations of transcripts in immune activation pathways, compared to WT-HFpEF hearts. In summary, our findings suggest that SARM1 may regulate immune activation pathways and promote HFpEF pathogenesis. We plan to determine the intricate relationships between immune dysregulation, metabolic stress, and cardiac dysfunction in HFpEF pathogenesis. The future direction may identify potential avenues for targeted therapeutic interventions aimed at modulating immune responses for HFpEF.

Uncovering the action mechanism of Shenqi Tiaoshen formula in the treatment of chronic obstructive pulmonary disease through network pharmacology, molecular docking, and experimental verification.

To reveal the potential underlying mechanism of the Shenqi Tiaoshen formula (, SQTS) in the treatment of chronic obstructive pulmonary disease (COPD) by utilizing network pharmacology, molecular docking, and experimental verification. Multiple open-source databases and research related to Traditional Chinese Medicine or compounds were employed to screen active ingredients and corresponding potential targets of the SQTS. The protein-protein interaction network screened hub genes, the relevant molecular mechanism and gene regulation were initially identified through the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis, and molecular docking was used to confirm further the interaction of the main components bound to the core targets. In vivo experiments on the COPD combined Qi-deficiency syndrome rat model were performed to verify the intervention effects and predicted potential molecular mechanisms of the SQTS. This study selected 156 active compounds and 326 candidate targets for treating COPD. Quercetin, Nobiletin, Kaempferol, Luteolin, Ginsenoside Rh2 and Formononetin were probably the main active compounds of SQTS in COPD treatment as they affected the most COPD-related targets, and interleukin-1 (IL-6), signal transducing activator of transcription 3 (STAT3), matrix metalloproteinase-9 (MMP9), vascular endothelial growth factor A (VEGFA), protein kinase B (AKT1), hypoxia-inducible factor-1α (HIF-1α), and forkhead box O3 (FoxO3) were identified as the hub genes associated with its therapeutic effect. KEGG analysis was mainly enriched in the signaling pathways closely related to inflammation, immunity and oxidative stress, such as HIF-1, tumor necrosis factor (TNF), phosphatidylinositol 3 kinase (PI3K)-AKT, FoxO, apoptosis, IL-17, and toll-like receptor. Molecular docking confirmed that the main active components shared a good affinity with the hub genes. In vivo experiments, the SQTS was found to improve the body weight, exhaustive swimming time, tail-hanging immobility time and struggle times, airway inflammation, lung functions, and inflammatory factors in the rat model of COPD. The up-regulation of p-PI3K, p-AKT, HIF-1α, FoxO3α, toll like receptor 4, VEGFA, Caspase 3, TNF-α, and IL-17 in COPD rats were down-regulated by SQTS, consistent with the network pharmacology results. This study provides evidence that the SQTS plays a critical role in anti-inflammation via suppressing immune inflammation and oxidative stress related pathways, indicating that the SQTS is a candidate herbal drug for further investigation in treating COPD.

Evaluating the Efficacy of Psycho-Behavioral Interventions for Cardiovascular Risk among People Living with HIV: A Systematic Review and Meta-Synthesis of Randomized Controlled Trials.

People with HIV (PWH) are disproportionately affected by cardiovascular disease (CVD). Psycho-behavioral therapies are capable of targeting the pathophysiology underlying HIV-CVD comorbidity. This study synthesized findings from randomized controlled trials (RCTs) of psycho-behavioral therapies for reducing CVD risk among PWH following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria were: (1) utilized an RCT design, (2) evaluated a cognitive-behavioral or mindfulness-based therapy, (3) sampled adults (age ≥18 years) with HIV, (4) measured a behavioral (e.g., diet) or biological (e.g., immune functioning) CVD risk factor, and (5) published in an English-language peer-reviewed journal. Electronic searches were conducted in six databases (e.g., MEDLINE) using controlled vocabulary and free-text synonyms for HIV, psycho-behavioral therapy, and CVD risk. Data were independently extracted with consensus reached. Outcomes were immune activation, tobacco-smoking, stress, inflammation, and physical activity from 33 studies. There were stronger effects for psycho-behavioral interventions compared to controls on CD4 (Hedge's g=0.262, 95% Confidence Interval [CI]=0.127, 0.396) and tobacco-smoking abstinence (Hedge's g=0.537, 95% CI=0.215, 0.86). There were no differences or insufficient data for stress, inflammation, or physical activity. No eligible studies examined psycho-behavioral interventions on blood pressure, lipids, or weight in PWH. There is increasing importance to further invest in broader CVD risk reduction effort for PWH that include psycho-behavioral intervention strategies.

A comprehensive overview of radiation therapy impacts of various cancer treatments and pivotal role in the immune system.

The cancer treatment landscape is significantly evolving, focusing on advanced radiation therapy methods to maximize effectiveness and minimize the adverse effects. Recognized as a pivotal component in cancer and disease treatment, radiation therapy (RT) has drawn attention in recent research that delves into its intricate interplay with inflammation and the immune response. This exploration unveils the underlying processes that significantly influence treatment outcomes. In this context, the potential advantages of combining bronchoscopy with RT across diverse clinical scenarios, alongside the targeted impact of brachytherapy, are explored. Concurrently, radiation treatments serve multifaceted roles such as DNA repair, cell elimination, and generating immune stress signaling molecules known as damage-associated molecular patterns, elucidating their effectiveness in treating various diseases. External beam RT introduces versatility by utilizing particles such as photons, electrons, protons, or carbon ions, each offering distinct advantages. Advanced RT techniques contribute to the evolving landscape, with emerging technologies like FLASH, spatially fractionated RT, and others poised to revolutionize the field. The comprehension of RT, striving for improved treatment outcomes, reduced side effects, and facilitating personalized and innovative treatments for cancer and noncancer patients. After navigating these advancements, the goal is fixed to usher in a new era in which RT is a cornerstone of precision and effectiveness in medical interventions. In summarizing the myriad findings, the review underscores the significance of understanding the differential impacts of radiation approaches on inflammation and immune modulation, offering valuable insights for developing innovative therapeutic interventions that harness the immune system in conjunction with RT.

Balancing roles between phosphatidylinositols and sphingolipids in regulating immunity and ER stress responses in pi4kβ1,2.

Plant immune regulation is complex. In addition to proteins, lipid molecules play critical roles in modulating immune responses. The mutant pi4kβ1,2 is mutated in two phosphatidylinositol 4-kinases PI4Kβ1 and β2 involved in the biosynthesis of phosphatidylinositol 4-phosphate (PI4P). The mutant displays autoimmunity, short roots, aberrant root hairs, and a heightened sensitivity to ER stress. In a forward genetic screen designed to dissect pi4kβ1,2 autoimmunity, we found that Orosomucoid-like 1 (ORM1) is required for the phenotypes of pi4kβ1,2, including short root and ER stress sensitivity. The orm1 mutations lead to increased long-chain base and ceramide levels in the suppressors. We also found that the basic region/leucine Zipper motif (bZIP) 28 and 60 transcription factors, central regulators of ER stress response, are required for its autoimmunity and root defect. In comparison, the defense-related phytohormones salicylic acid (SA) and N-hydroxypipecolic acid (NHP) are required for its autoimmunity but plays a minor role in its root phenotypes. Further, we found that wild-type plants overexpressing ORM1 are autoimmune, displaying short roots and increased ceramide levels. The autoimmunity of the ORM1 overexpression lines is dependent on SA, NHP, and bZIP60. As ORM1 is a known negative regulator of sphingolipid biosynthesis, our study uncovers a balancing role between PIs and sphingolipids in regulating immunity and ER stress responses in pi4kβ1,2.

Effects of adding antibiotics to an inactivated oil-adjuvant avian influenza vaccine on vaccine characteristics and chick health

During poultry immunization, antibiotics are typically added to inactivated oil-adjuvant avian influenza (AI) vaccines. Here, we evaluated the effects of adding ceftiofur, a third-generation cephalosporin, to an AI vaccine on vaccine stability and structure and on chick growth, immune efficacy, blood concentrations, biochemical and immunological indices, and gut microbiota. The results demonstrated that neither aqueous ceftiofur sodium nor ceftiofur hydrochloride oil emulsion formed a stable mixture with the vaccine. Adding ceftiofur formulations, particularly ceftiofur hydrochloride, at >4% significantly destabilized the vaccine's water-in-oil structures. Adding ceftiofur also increased vaccine malabsorption at the injection site; specifically, adding ceftiofur hydrochloride reduced H5N8 and H7N9 antibody titers after the first immunization (P < 0.05) and H7N9 antibody titers after the second immunization (P < 0.01). Serum drug concentrations did not differ significantly between the groups with ceftiofur sodium and hydrochloride addition. Ceftiofur addition increased postvaccination chick weight loss; compared with the vaccine alone, ceftiofur sodium-vaccine mixture increased chick weight significantly (P < 0.05). Ceftiofur addition also increased stress indices and reduced antioxidant capacity significantly (P < 0.05 or P < 0.01). Vaccination-related immune stress reduced gut microbiota diversity in chicks; ceftiofur addition reversed this change. AI vaccine immunization significantly reduced the relative abundance of Lactobacillus and Muribaculaceae but significantly increased that of Bacteroides and Eubacterium coprostanoligenes group. Ceftiofur addition restored the gut microbiota structure; in particular, ceftiofur hydrochloride addition significantly increased the abundance of the harmful gut microbes Escherichia-Shigella and Enterococcus, whereas ceftiofur sodium addition significantly reduced it. The changes in gut microbiota led to alterations in metabolic pathways related to membrane transport, amino acids, and carbohydrates. In conclusion, adding ceftiofur to the AI vaccine had positive effects on chick growth and gut microbiota modulation; however, different antibiotic concentrations and formulations may disrupt vaccine structure, possibly affecting vaccine safety and immunization efficacy. Thus, the addition of antibiotics to oil-adjuvant vaccines is associated with a risk of immunization failure and should be applied to poultry with caution.

Mechanisms of stress-attributed breast cancer incidence and progression.

Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths in women, with psychosocial stress commonly cited by patients as one of its causes. While there is conflicting epidemiological evidence investigating the association between psychosocial stress and breast cancer incidence and progression, there is reason to believe that interventions aimed at reducing stress pharmacologically or psychologically may improve breast cancer outcomes. The aim of this review is to discuss the molecular and biological mechanisms of stress-attributed breast cancer incidence and progression, including the induction of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS), as well as decreased immune function and stress hormone-induced resistance to chemotherapy. Moreover, these mechanisms have been cited as potential therapeutic targets of pharmacologic and psychological interventions that may improve the care, well-being and survival of breast cancer patients. Further research is recommended to investigate whether interventions in the primary care setting for women with risk factors for breast cancer development may lead to a decreased incidence of invasive breast tumors.

A Carrier-Based Quantitative Proteomics Method Applied to Biomarker Discovery in Pericardial Fluid

Data-dependent liquid chromatography tandem mass spectrometry is challenged by the large concentration range of proteins in plasma and related fluids. We adapted the SCoPE method from single-cell proteomics to pericardial fluid, where a myocardial tissue carrier was used to aid protein quantification. The carrier proteome and patient samples were labeled with distinct isobaric labels, which allowed separate quantification. Undepleted pericardial fluid from patients with type 2 diabetes mellitus and/or heart failure undergoing heart surgery was analyzed with either a traditional liquid chromatography tandem mass spectrometry method or with the carrier proteome. In total, 1398 proteins were quantified with a carrier, compared to 265 without, and a higher proportion of these proteins were of myocardial origin. The number of differentially expressed proteins also increased nearly four-fold. For patients with both heart failure and type 2 diabetes mellitus, pathway analysis of upregulated proteins demonstrated the enrichment of immune activation, blood coagulation, and stress pathways. Overall, our work demonstrates the applicability of a carrier for enhanced protein quantification in challenging biological matrices such as pericardial fluid, with potential applications for biomarker discovery. Mass spectrometry data are available via ProteomeXchange with identifier PXD053450.

Intracellular Polysaccharides of Eurotium cristatum Exhibited Anticolitis Effects in Association with Gut Tryptophan Metabolism.

This study is to investigate the protective effects of Eurotium cristatum intracellular polysaccharides (ECIP) on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC). The oral administration of ECIP could downregulate the disease activity index (DAI) and ameliorate the colonic shortening, immune stress, and damage caused by DSS. In addition, ECIP treatment increased the colonic contents of SCFAs including acetic, propionic, and butyric acids in UC mice. Targeted and untargeted metabolic analysis suggested that ECIP dramatically altered the tryptophan metabolism in the feces of UC mice and promoted the conversion of tryptophan into indole metabolites including indolepyruvate and indole-3-acetic acid (IAA) and indolealdehyde (IAId). Moreover, ECIP observably increased the content of colonic IL-22 and stimulated the relative concentration and relative expression of tight junction molecules in mRNA and proteins levels. Conclusively, consumption of ECIP can improve colon damage and its related effects of UC by promoting the production of IAA and IAId to reinforce intestinal barriers.

Identification of immune- and oxidative stress-related signature genes as potential targets for mRNA vaccines for pancreatic cancer patients.

Adenocarcinoma of the pancreas (PAAD) is one of the deadliest malignant tumors, and messenger ribonucleic acid vaccines, which constitute the latest generation of vaccine technology, are expected to lead to new ideas for the treatment of pancreatic cancer. The Cancer Genome Atlas-PAAD and Genotype-Tissue Expression data were merged and analyzed. Weighted gene coexpression network analysis was used to identify gene modules associated with tumor mutational burden among the genes related to both immunity and oxidative stress. Differentially expressed immune-related oxidative stress genes were screened via univariate Cox regression analysis, and these genes were analyzed via nonnegative matrix factorization. After immune infiltration analysis, least absolute shrinkage and selection operator regression combined with Cox regression was used to construct the model, and the usefulness of the model was predicted based on the receiver operating characteristic curve and decision curve analysis curves after model construction. Finally, metabolic pathway enrichment was analyzed using gene set enrichment analysis combined with Kyoto Encyclopedia of Genes and Genomes and gene ontology biological process analyses. This model consisting of the ERAP2, mesenchymal-epithelial transition factor (MET), CXCL9, and angiotensinogen (AGT) genes can be used to help predict the prognosis of pancreatic cancer patients more accurately than existing models. ERAP2 is involved in immune activation and is important in cancer immune evasion. MET binds to hepatocyte growth factor, leading to the dimerization and phosphorylation of c-MET. This activates various signaling pathways, including MAPK and PI3K, to regulate the proliferation, invasion, and migration of cancer cells. CXCL9 overexpression is associated with a poor patient prognosis and reduces the number of CD8 + cytotoxic T lymphocytes in the PAAD tumor microenvironment. AGT is cleaved by the renin enzyme to produce angiotensin 1, and AGT-converting enzyme cleaves angiotensin 1 to produce angiotensin 2. Exposure to AGT-converting enzyme inhibitors after pancreatic cancer diagnosis is associated with improved survival. The 4 genes identified in the present study - ERAP2, MET, CXCL9, and AGT - are expected to serve as targets for messenger ribonucleic acid vaccine development and need to be further investigated in depth.

Growth on Douglas fir media facilitates Cryptococcus virulence factor production and enhances fungal survival against environmental and immune stressors.

The yeasts Cryptococcus neoformans and Cryptococcus gattii are fungal pathogens that can be isolated from the environment, including the surfaces of many plants. Cryptococcus gattii caused an outbreak on Vancouver Island, British Columbia beginning in 1999 that has since spread to the Pacific Northwest of the United States. Coastal Douglas fir (Pseudotsuga menziesii) is an important lumber species and a major component of the ecosystems in this area. Previous research has explored Cryptococcus survival and mating on Douglas fir plants and plant-derived material, but no studies have been done on the production of cryptococcal virulence factors by cells grown on those media. Here, we investigated the effects of growth on Douglas fir-derived media on the production of the polysaccharide capsule and melanin, two of the most important cryptococcal virulence factors. We found that while the capsule was mostly unchanged by growth in Douglas fir media compared to cells grown in defined minimal media, Cryptococcus spp. can use substrates present in Douglas fir to synthesize functional and protective melanin. These results suggest mechanisms by which Cryptococcus species may survive in the environment and emphasize the need to explore how association with Douglas fir trees could affect its epidemiology for human cryptococcosis.