Despite the growing interest in the use of probiotics in broilers as feed additives, studies conducted to investigate the effect of probiotic administration on acute phase responses and the impact on muscle growth parameters in broilers are still limited. In this study, we investigated the effect of Bacillus amyloliquefaciens CECT 5940 on relative gene expression for growth factors involved in muscle development (insulin-like growth factors, myogenic factor 5, paired-box transcription factor), percentage of proliferating antigen cell nuclei in breast muscle, and secretion of acute phase proteins (serum amyloid A, haptoglobin, alpha1-acid glycoprotein) in the peripheral blood of broilers. Sixty one-day-old chicks from the experimental group were sprayed with a probiotic containing B. amyloliquefaciens at a dose of 1 × 1010 CFU/g directly after hatching and received the probiotic in drinking water (50 × 1010 CFU/1000 L) for 5 consecutive days of life. Sampling was performed on the 5th, 8th, and 12th day of life of the chicks. From the obtained results, we can conclude that B. amyloliquefaciens modulated the gene expression of selected growth parameters in the pectoral muscle, thereby increasing the number of satellite cells, however, their uptake into muscle fibers and thus increased hypertrophic growth was not proven at the time of the last sampling. At the same time, it demonstrated a potentiating effect on PCNA expression in chicken breast muscles in the early intensive growth phase of broiler chickens and modulated the production of acute phase proteins, which may contribute to improving adaptive processes during the growth and development of broilers.

Celiac disease (CD) is a chronic autoimmune disorder characterized by an abnormal immune response to gluten, leading to intestinal inflammation and various clinical manifestations. Serum proteins are increasingly recognized as potential biomarkers in CD, reflecting inflammation, malabsorption, and immune activation.

This review aims to elucidate the role of serum proteins in the pathogenesis, diagnosis, and management of CD, emphasizing their potential as noninvasive biomarkers and therapeutic targets.

A comprehensive review of current literature was conducted, focusing on key serum proteins such as albumin, transthyretin (TTR), transferrin, β2-microglobulin (β2M), C-reactive protein (CRP), and immunoglobulins. Their alterations in CD and their relevance to disease activity, nutritional status, and treatment response were examined.

CD-related inflammation leads to increased acute-phase proteins (e.g., CRP) and decreased transport proteins (e.g., albumin, TTR, transferrin), contributing to malnutrition and anemia. TTR serves as a sensitive marker of nutritional status, while transferrin levels correlate with iron deficiency, a common CD complication. Immunoglobulin profiles reflect immune responses to gluten. These proteins provide insights into CD pathophysiology and offer potential utility for diagnosis and monitoring.

Serum proteins represent promising biomarkers for CD diagnosis and management, with potential for integration into clinical practice. Further research is necessary to validate their utility in routine patient care and explore their role in personalized therapeutic strategies.

Necrotic enteritis (NE) in broiler chickens is caused by the overgrowth of toxin-producing strains of Clostridium (C.) perfringens. This study aims to analyze the blood proteome of broiler chickens affected by NE, providing insights into the host's response to the infection. Using MS/MS-based proteomics, blood plasma samples from broilers with necrotic lesions of different severity were analyzed and compared to healthy controls. A total of 412 proteins were identified, with 63 showing significant differences; for 25 of those correlation with disease severity was observed. Functional analysis revealed that proteins affected by NE were predominantly associated with the immune and signaling processes and extracellular matrix (ECM) structures. Notably, regulated proteins were significantly involved in bioprocesses related to complement activation, acute phase reaction, proteolysis and humoral immune response. The proteomics findings suggest that the changes in plasma proteins in response to NE are driven by the host's intensified efforts to counteract the infection, demonstrating a.o. activation of ECM-degrading proteases (MMP2, TIMP2), acute phase response (HPS5, CP, EXFABP, TF, VNN) and notable reduction in basement membrane (BM) and ECM-related peptides (PLOD2, POSTN, COL1A1/2, HSPG2, NID2) detected in the blood of NE-affected birds. Moreover, the findings underscore a coordinated effort of the host to mitigate the C. perfringens infection via activating immune (a.o., C3, CFH, MASP2, MBL2) and acute phase (CP, ORM, TF, ExFAB) related proteins. This study provides a deeper understanding of the host-pathogen interactions and identifies potential biomarkers and targets for therapeutic intervention. Data are available via ProteomeXchange with identifier PXD054172.

Apolipoprotein E (APOE- gene; apoE- protein) is the strongest genetic modulator of late-onset Alzheimer's disease (AD), with its three major isoforms conferring risk for disease ε2 < ε3 < ε4. Emerging protective gene variants, such as APOE Christchurch and the COLBOS variant of REELIN, an alternative target of certain apoE receptors, offer novel insights into resilience against AD. In recent years, the role of apoE has been shown to extend beyond its primary function in lipid transport, influencing multiple biological processes, including amyloid-β (Aβ) aggregation, tau pathology, neuroinflammation, autophagy, cerebrovascular integrity and protection from lipid peroxidation and the resulting ferroptotic cell death. While the detrimental influence of apoE ε4 on these and other processes has been well described, the molecular mechanisms underpinning this disadvantage require further enunciation, particularly to realize therapeutic opportunities related to apoE. This review explores the multifaceted roles of apoE in AD pathogenesis, emphasizing recent discoveries and translational approaches to target apoE-mediated pathways. These findings underscore the potential for apoE-based therapeutic strategies to prevent or mitigate AD in genetically at-risk populations.

This study examined the intestinal mucosal immune responses elicited by an oral hydrogel-encapsulated multivalent Vibrio vaccine in Asian seabass (Lates calcarifer) to protect against vibriosis caused by Vibrio harveyi, V. vulnificus, and Photobacterium damselae (formerly Vibrio damsela). Both 7-day and 14-day oral vaccination regimens effectively enhanced innate and adaptive immune responses while supporting gut recovery post-infection. Transcriptomic analyses of intestines from fish that received consecutive 7- and 14-day vaccination regimens, followed by co-infection with multistrain Vibrio spp., revealed significant upregulation of innate and specific immune markers at week 8 post-vaccination. These responses were further bolstered by a strong adaptive immune activation, characterized by T-cell and B-cell receptor signaling as well as antibody production. In addition, the vaccine also demonstrated cross-protective immunomodulatory effects, evidenced by elevated interferon-related pathways (e.g., IFNAR2 and IFN-induced proteins), suggesting its potential to protect against co-infecting pathogens, a critical advantage in aquaculture systems facing diverse pathogen pressures. Beyond immune activation, the involvement proteins of TGF-β family members, including BMP3 and BMP4, highlights the vaccine's role in tissue repair and remodeling. These responses likely mitigate epithelial damage and preserve gut barrier integrity post-infection, showcasing the dual benefits of immunoprotection and post-infection recovery. The findings highlight the oral hydrogel-encapsulated multivalent Vibrio vaccine's ability to enhance immunity against specific bacterial pathogens while offering broader immunomodulatory and tissue-repair benefits. Its cross-protective and recovery-supporting properties make it a promising solution for sustainable aquaculture practices, effectively addressing pathogen control and boosting host resilience.

Autoimmune thyroid disease (AITD) is associated with other autoimmune endocrine diseases such as type 1 diabetes (T1D) and celiac disease (CeD). Thyroid peroxidase autoantibodies (TPOA) are biomarkers of AITD but may also occur in patients with other autoimmune diseases. We examined cross-sectional correlations between TPOA and an array of immune markers in a cohort of 90 children with exclusively T1D (n = 27), CeD (n = 16) or a combination of these two diseases (n = 18), compared to a reference group of children without these diagnoses (n = 29). Children with exclusively T1D or T1D in combination with CeD had higher levels of TPOA with an overrepresentation among girls. The correlations between immune markers and TPOA were distinctly different between all study groups. In children with T1D, TPOA correlated mainly with the T helper 1 associated IFN-γ and pro-inflammatory IL-1β. In contrast, in children with combined diagnoses, TPOA was correlated with pro-inflammatory MCP-1, the acute phase proteins ferritin, fibrinogen, and serum albumin A, and adipocytokines resistin and visfatin. Children with exclusively CeD did not show the same strong association between immune markers and TPOA. In conclusion, TPOA positivity was mainly detected in patients with T1D and female sex. Several inflammatory markers correlated with TPOA, indicating a relation to autoimmune parameters in children with T1D, CeD or both, but preceding symptoms AITD.

A cytokine storm is marked by excessive pro-inflammatory cytokine release, and has emerged as a key factor in severe COVID-19 cases - making it a critical therapeutic target. However, its pathophysiology was poorly understood, which hindered effective treatment. SARS-CoV-2 initially disrupts angiotensin signalling, promoting inflammation through ACE-2 downregulation. Some patients' immune systems then fail to shift from innate to adaptive immunity, suppressing interferon responses and leading to excessive pyroptosis and neutrophil activation. This amplifies tissue damage and inflammation, creating a pro-inflammatory loop. The result is the disruption of Th1/Th2 and Th17/Treg balances, lymphocyte exhaustion, and extensive blood clotting. Cytokine storm treatments include glucocorticoids to suppress the immune system, monoclonal antibodies to neutralize specific cytokines, and JAK inhibitors to block cytokine receptor signalling. However, the most effective treatment options for mitigating SARS-CoV-2 infection remain vaccines as a preventive measure and antiviral drugs for the early stages of infection. This article synthesizes insights into immune dysregulation in COVID-19, offering a framework to better understand cytokine storms and to improve monitoring, biomarker discovery, and treatment strategies for COVID-19 and other conditions involving cytokine storms.

The first year of life represents a dynamic immune development period that impacts the risk of developing respiratory-related diseases, including asthma, recurrent infections, and eczema. However, the role of immune-mediating proteins in childhood respiratory diseases is not well characterized in early life.

The objective of this study was to investigate relationships between protein profiles at age 1 year and respiratory-related diseases by age 6 years, including asthma, recurrent wheeze, respiratory infections, and eczema.

We applied weighted gene correlation network analysis to derive modules of highly correlated proteins during early life immune development using plasma samples collected from children at age 1 year (n = 294) in the Vitamin D Antenatal Asthma Reduction Trial. Using regression analysis, we evaluated relationships between protein modules at age 1 and respiratory-related diseases by age 6. We integrated protein modules with additional omics and social, demographic, and environmental data for further characterization.

Our analysis identified 4 protein modules at age 1 year associated with incidence of childhood asthma and/or recurrent wheeze (adjusted Ps = .02 to .03), respiratory infections (adjusted Ps = 6.3 × 10-9 to 2.9 × 10-6), and eczema (adjusted P = .01) by age 6 years; associations between modules and clinical outcomes were temporally sensitive and were not recapitulated using protein profiles at age 6 years. Age 1 modules were associated with environmental factors (adjusted Ps = 2.8 × 10-10 to .03) and alterations in metabolomic pathways (adjusted Ps = 2.8 × 10-6 to .04). No genome-wide single nucleotide polymorphisms were identified for any protein module.

These findings suggested that protein profiles at age 1 year predicted development of respiratory-related diseases by age 6. Applying network approaches to study protein profiles may represent a new strategy to identify children susceptible to respiratory-related diseases in the first year of life.

The acute phase response is a hallmark of all inflammatory reactions and acute phase reactants, such as C-reactive protein (CRP) and serum amyloid A (SAA) proteins, are among the most useful plasma and serum markers of inflammation in clinical medicine. Although it is well established that inflammatory cytokines, mainly interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) induce SAA in the liver, the biological functions of elicited SAA remain an enigma. By the classical multi-step protein purification studies of chemotactic factors present in plasma or serum, we discovered novel chemokines and SAA1 fragments, which are induced during inflammatory reactions. In contrast to earlier literature, pure SAA1 fails to induce chemokines, an ascribed function that most probably originates from contaminating lipopolysaccharide (LPS). However, intact SAA1 and fragments thereof synergize with CXC and CC chemokines to enhance chemotaxis. Natural SAA1 fragments are generated by inflammatory proteinases such as matrix metalloproteinase-9 (MMP-9). They mediate synergy with chemokines by the interaction with cognate G protein-coupled receptors (GPCRs), formyl peptide receptor 2 (FPR2) and (CC and CXC) chemokine receptors. In conclusion, SAA1 enforces the action of many chemokines and assists in local leukocyte recruitment, in particular, when the concentrations of specifically-induced chemokines are still low.

Orofacial pain conditions, including temporomandibular disorder, migraine, dental pain, and trigeminal neuralgia, are complex, multifactorial disorders with significant impacts on patients' quality of life. As understanding of the pathophysiology of these conditions has deepened, the role of molecular and genetic biomarkers in diagnosing, monitoring, and potentially treating orofacial pain has garnered increasing interest. This scoping review provides a comprehensive overview of the current state of research on biomarkers associated with orofacial pain conditions. By analyzing existing literature, we identify key biomarkers linked to inflammation, neural activity, and tissue degradation that are common across multiple conditions, as well as those specific to particular disorders. Our findings underscore the potential of these biomarkers to guide the development of personalized therapeutic strategies. However, the review also highlights the challenges faced by current biomarker research, including heterogeneity in study designs, small sample sizes, and a lack of longitudinal data. Addressing these challenges is critical for translating biomarker research into clinical practice and improving outcomes for patients with orofacial pain.

The purpose of this experiment was to evaluate the transference of passive immunity (TPI) and growth achieved by calves born to dams with low or high SCC at dry-off and fed with colostrum from cows with low or high SCC at dry-off. Forty multiparous (3.2 lactations; SD = 1.1), dry, and pregnant Holstein cows were used. The cows were separated into 2 groups based on the SCC in the last 3 monthly records before dry-off. An SCC of 200,000 cells/mL was used as the cut-off point to categorize cows with or without mastitis at dry-off, and 2 groups of 20 cows each were formed: L-cow cows (last 3 SCC before dry-off less than 200,000 cells/mL) and H-cow cows (last 3 SCC before dry-off greater than 200,000 cells/mL). At calving, 40 calves were obtained (20 calves born to L-cow cows [L-calf], and 20 calves born to H-cow cows [H-calf]; females = 21 and males = 19), and 40 colostrum units (20 from L-cow cows [L-col]; and 20 from H-cow cows [H-col]). The experimental design was a 2 × 2 factorial, with 2 factors and 2 levels within each factor (type of calf: L-calf and H-calf, and type of colostrum: L-col and H-col), determining 4 treatments (n = 10 per treatment): L-calfxL-col (L-calf fed with L-col); L-calfxH-col (L-calf fed with H-col); H-calfxL-col (H-calf fed with L-col); and H-calfxH-col (H-calf fed with H-col). Male and female calves were homogeneously distributed within each treatment. All calves received 4 L of colostrum, L-col or H-col depending on the assigned treatment, with an oro-esophageal tube within 3 h after birth. Yield, chemical composition and IgG were determined. The TPI and the apparent efficiency of IgG absorption (AEA) were also determined. Nutrient intake and body growth and development traits of the calves (BW, heart girth, and withers height) were determined in the first 30 d of life. The colostrum produced by L-cow presented a lower SCC compared with H-cow. Colostrum protein yield of L-cow was 0.21 kg higher than H-cow, and colostrum of L-cow had 24% higher IgG concentration. The TPI was not affected by the interaction calf type × colostrum type, and there was no effect of the colostrum type on the level TPI and AEA achieved by calves. However, an effect of calf type on TPI and AEA achieved was observed, as L-calf achieved greater TPI than H-calf (28.8 and 22.8 g IgG/L, respectively; SEM = 1.5), and L-calf presented a higher AEA than H-calf (30.0% and 24.5%, respectively; SEM = 1.4). The BW, heart girth, and withers height were not affected by calf type, colostrum type, or by the interaction calf type × colostrum type. We concluded that cows with high SCC at dry-off produced colostrum with higher SCC and lower IgG concentrations, but when ingested by calves it did not affect TPI, feed intake, growth, or development. Calves born to cows with high SCC at dry-off presented a lower AEA of IgG, which translated into a lower serum concentration of IgG, irrespective of type of colostrum that was fed.

Infection with Mycobacterium tuberculosis (Mtb) triggers an autoimmune-like response in the host leading to further complications. One of the major concerns in eliminating Tuberculosis (TB) is identifying individuals with Latent Tuberculosis Infection (LTBI) who serve as major reservoirs of Mtb making them the important target group for TB eradication. Since no gold standard tests are available for detecting LTBI, the global burden of LTBI cannot be precisely determined. Since LTBI poses several challenges to worldwide healthcare, managing LTBI must be the key priority to achieve a TB-free status. The inflammatory mediators play a major role in determining the outcome of the Mtb infection and also their levels seem to change according to the disease severity. Identification of inflammatory mediators and utilizing them as diagnostic biomarkers for detecting the various stages of TB disease might help identify the reservoirs of Mtb infection even before they become symptomatic so that preventative treatment can be started early. In summary, this review primarily focuses on exploring different inflammatory markers along the course of the Mtb infection. Identifying LTBI-specific biomarkers helps to identify individuals who are at higher risk of developing TB and preparing them to adhere to preventive therapy thus minimizing the global burden of TB.

EBUS-TBNA is the most common interventional pulmonology procedure performed globally and remains the cornerstone of the diagnosis and staging not only of lung cancer but also for other neoplastic, inflammatory, and infective pathologies of the mediastinum. Infective complications of EBUS-TBNA are underreported in the literature, but the constantly rising incidence of lung cancer is leading to an increasing number of EBUS-TBNA procedures and, therefore, to a significant number of infective complications, even 4 weeks following the procedure. In this review we attempt to summarize the risk factors related to these infective complications, along with useful biomarkers that can be used to identify patients that might develop infective complications, to facilitate the prediction or even prompt treatment of these.

Lesioned fascicles (LFs) in the sciatic nerves of individuals with diabetic neuropathy (DN) correlate with clinical symptom severity. This study aimed to characterize the structural and molecular composition of these lesions to better understand DN pathogenesis. Sciatic nerves from amputees with and without type 2 diabetes (T2D) were examined using ex vivo magnetic resonance neurography, in vitro imaging, and proteomic analysis. Lesions were only found in T2D donors and exhibited significant structural abnormalities, including axonal degeneration, demyelination, and impaired blood-nerve barrier (BNB). Although non-LFs from T2D donors showed activation of neuroprotective pathways, LFs lacked this response and instead displayed increased complement activation via the classical pathway. The detection of liver-derived acute-phase proteins suggests that BNB disruption facilitates harmful interorgan communication between the liver and nerves. These findings reveal key molecular mechanisms contributing to DN and highlight potential targets for therapeutic intervention.

We aimed to investigate the potential of altered levels of various acute phase proteins (APPs) in the plasma, either used alone or in combination with ultrasound-, clinical-, and conventional blood-based tests, for predicting the risk of intra-amniotic inflammation (IAI), microbial invasion of the amniotic cavity (MIAC), histologic chorioamnionitis (HCA), and funisitis in women with preterm premature rupture of membranes (PPROM).

A total of 195 consecutive pregnancies involving singleton women with PPROM (at 23 + 0-34 + 0 weeks) who underwent amniocentesis and from whom plasma samples were obtained at amniocentesis were retrospectively included in this study. Amniotic fluid (AF) was cultured to assess the MIAC and analyzed for interleukin (IL)-6 levels to define IAI (AF IL-6 level of ≥2.6 ng/mL). The plasma concentrations of hepcidin, mannose-binding lectin (MBL), pentraxin-2, retinol-binding protein 4 (RBP4), serum amyloid A1 (SAA1), and serpin A1 were determined using ELISA. Ultrasonographic cervical length (CL), neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein levels were measured. IAI/MIAC was defined as IAI, MIAC, or both.

Multivariate logistic regression analyses showed the following: (1) elevated plasma levels of hepcidin and SAA1 and decreased levels of RBP4 in the plasma were independently associated with IAI/MIAC and (2) decreased plasma RBP4 levels were independently associated with funisitis; however, (3) none of the plasma APPs investigated were associated with acute HCA when adjusted for baseline covariates. Using stepwise regression analysis, noninvasive prediction models comprising plasma RBP4 levels, CL, NLR, and gestational age at sampling were proposed, which provided a good prediction of IAI/MIAC and funisitis (area under the curve: 0.80 and 0.72, respectively).

Hepcidin, RBP4, and SAA1 were identified as potential APP biomarkers in the plasma predictive of IAI/MIAC or funisitis in patients with PPROM. In particular, combination of these APP biomarkers with ultrasound-, clinical-, and conventional blood-based markers can significantly support the diagnosis of IAI/MIAC and funisitis.

Breeding animals to produce more robust and disease-resistant pig populations becomes a complementary strategy to the more conventional methods of biosecurity and vaccination. The objective of this study was to explore the ability of a panel of genetic markers and immunity parameters to predict the survival rates during a natural PRRSV outbreak. Ten-week-old female Duroc pigs (n = 129), obtained from 61 sows and 20 boars, were naturally infected with a highly pathogenic PRRSV genotype 1 strain. Prior to infection, piglets were screened for immunity parameters (IgG levels in plasma and SOX13 mRNA expression in blood) and genetic markers previously associated to PRRSV immune response and immunity traits. Additionally, the 20 boars were genotyped with a panel of 132 single nucleotide polymorphisms (SNPs). Survival analysis showed that mortality was significantly higher for animals with low basal IgG levels in plasma and/or high SOX13 mRNA expression in blood. The genotypes of sires for SNPs associated with IgG plasma levels, CRP in serum, percentage of γδ T cells, lymphocyte phagocytic capacity, total number of lymphocytes and leukocytes, and MCV and MCH were significantly associated with the number of surviving offspring. Furthermore, CD163 and GBP5 markers were also associated to piglet survival. The effects of these SNPs were polygenic and cumulative, survival decreased from 94 to 21% as more susceptible alleles were accumulated for the different markers. Our results confirmed the existence of genetic variability in survival after PRRSV infection and provided a set of genetic markers and immunity traits associated with PRRS resistance.

Successful treatment of infectious diseases requires a multiprong approach involving strategies that limit pathogen burdens and that limit disease. Traditionally, disease defense is thought to be a direct function of pathogen killing, and thus, our current methods for treating infections have largely relied on pathogen eradication, leading to drug resistance. Strategies that target the virulence of the pathogen, called antivirulence, have been proposed to be a necessary strategy to integrate into our infectious disease toolbox to promote disease defense and alleviate the burden of drug resistance. Traditional antivirulence strategies have largely focused on developing compounds that directly target microbial virulence factors or products to impair their ability to initiate and sustain infection. As virulence is linked to pathogen fitness, simply targeting a virulence factor may not be sufficient to overcome the ability of pathogens evolving resistance. In this review, I discuss co-operative defenses that hosts have evolved to promote antivirulence mechanisms that suppress pathogen virulence without having a negative impact on pathogen fitness. I also discuss the different definitions antivirulence has been assigned over the years and suggest a more holistic one. Co-operative defenses remain an underexplored resource in medicine, and by learning from how hosts have evolved to promote antivirulence, we have the potential to develop disease defense interventions without the risk of pathogens developing drug resistance.

Background and Objectives: The use of temporary left ventricular assist devices (tLVADs) for patients suffering from cardiogenic shock (CS) is becoming more common. This study examines the indications and outcomes of microaxial flow pumps (Impella®, Abiomed Inc., Danvers, MA, USA) when cannulated through the axillary artery in patients with severe CS, with a particular focus on acute phase reactions and hemolytic responses. Materials and Methods: This single-center, retrospective cohort involved patients who received microaxial Impella implantation via the axillary artery from 2020 to 2022 (n = 47). Results: Among the patients, 66% (N = 31 cases) were treated with the Impella 5.5, 25.5% (N = 12 cases) with the Impella 5.0, and 8.5% (N = 4 cases) with the Impella CP. Additionally, 28% were managed using the ECMELLA concept. The mean length of time for Impella support was 8 days. The overall 30-day survival rate was 78%, with no significant differences observed between the ECMELLA group and the various Impella types. At 30 days post-therapy, 47% of survivors no longer required mechanical support, while 26% were upgraded to a durable LVAD. Interleukin-6 (IL-6) levels were significantly lower in patients receiving Impella 5.5 (n = 17 vs. 12) immediately following implantation (p = 0.03) compared with those with smaller devices. Haptoglobin levels were significantly higher in the Impella 5.5 group (n = 17 vs. 11, p = 0.02), with overall lower rates of hemolysis (45.1%, p < 0.01). Conclusions: The mortality rate in critical CS appears reduced with axillary artery implantation of Impella devices relative to existing literature. A full-flow microaxial pump (Impella 5.5) seems advantageous regarding systemic inflammatory response syndrome (SIRS) and acute hemolysis, indicated by lower IL-6 and higher haptoglobin levels, compared with smaller Impella devices. A tailored escalation/de-escalation concept using axillary access for different mAFP types appears feasible and safe.

Stress associated with changes in host immunity occurs in response to altered environmental conditions, endogenous imbalances, infectious agents and harmful stimuli. The importance of genetic diversity in chickens has increased due to individual immune differences towards resistance and susceptibility to various stimuli.

This study aimed to investigate the association of major histocompatibility complex (MHC) polymorphism with acute phase response (APR) in Ross 308 broiler chickens.

The allelic diversity of the LEI0258 microsatellite marker was determined in 120 Ross broilers. In addition, acute phase proteins (APPs), including serum amyloid A (SAA) and alpha-1-acid glycoprotein (AGP), were analysed as markers of the APR. Furthermore, leukocyte count and the heterophil/lymphocyte ratio (H/L ratio) were examined. The antibody response to the Newcastle disease vaccine (NDV) was also measured to assess humoral mediated immunity. Lastly, the correlation between immune responses and MHC alleles was investigated to identify the most effective alleles in a stress-related situation.

A total of six alleles, ranging from 195 to 448 bp, were identified. Association study revealed a significant influence of MHC alleles on APPs in Ross population (p < 0.05). Notably, Allele 448 had a significant correlation with SAA concentration and the H/L ratio. Allele 207 displayed a positive association with AGP concentration, whereas Allele 195 showed a negative association. Furthermore, a significant association was observed between Allele 448 and basopenia, as well as between Allele 195 and monocytosis.

Results confirmed the significance of MHC as a candidate gene marker for immune responses, which supports its use for vaccine design, genetic improvement of disease-resistant traits and resource conservation in commercial broiler chickens.

Intrauterine infection is one of the most jeopardizing conditions associated with adverse outcomes, including preterm birth; however, multiple tolerance mechanisms operate at the maternal-fetal interface to avoid the rejection of the fetus. Among the factors that maintain the uterus as an immunoprivileged site, Galectin-1 (Gal-1), an immunomodulatory glycan-binding protein secreted by the maternal-fetal unit, is pivotal in promoting immune cell homeostasis. This work aimed to evaluate the role of Gal-1 during a lipopolysaccharide (LPS)-induced-inflammatory milieu.

Using an ex vivo culture with two independent compartments, human fetal membranes at term were pretreated with 40 and 80 ng/mL of Gal-1, then to reproduce an intraamniotic inflammation, the fetal side of membranes was stimulated with 500 ng/mL of LPS for 24 h. The concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein (MCP1), macrophage inflammatory protein (MIP1) α, regulated upon activation normal T cell expressed and secreted (RANTES), and matrix metalloproteinase (MMP)-9 were measured in both amnion and choriodecidua compartments.

In a tissue-specific fashion profile, pretreatment with the physiologic concentration of Gal-1 significantly diminished the LPS-dependent secretion of TNF-α, IL-1β, Il-6, MCP1, MIP1α, RANTES, and MMP-9.

Gal-1 elicits an anti-inflammatory effect on the human fetal membranes stimulated with LPS, which supports the hypothesis that Gal-1 is part of the immunomodulatory mechanisms intended to stop the harmful effect of inflammation of the maternal-fetal interface.

This study aims to investigate the effects of Procalcitonin, Tumor Necrosis Factor-alpha, Interleukin-6, and Haptoglobin levels on the prognosis of calves classified according to the severity of diarrhea. The animal material comprised 48 diarrheic calves of different breeds and sexes, aged 1-30 days, and 16 healthy calves aged 1-30 days. The 48 diarrheic calves used were divided into 3 groups, each consisting of 16 calves. Group 1 was designed as Viral (Rota + Corona n = 16), Group 2 as Bacterial (E. coli n = 16), and Group 3 as Parasitic (Cryptosporidiosis n = 16). Each of these groups was further divided into 2 subgroups (moderate and severe subgroups). Blood samples were taken from the diarrheic calves before treatment (0 h) and at 24 and 72 h after treatment. Complete blood count, biochemical, blood gas analyses, and ELISA tests were performed. It was determined that 18.75 % (9/48) of the 48 diarrheic calves included in the study died, while 81.25 % (39/48) survived. The highest mortality rate among the patient groups was observed in the severe rota + corona group (37.5 %). The average PCT concentration in the diarrheic calves in the Rota-corona and E. coli groups at 0 and 24 hours was found to be higher than both the healthy calves and the diarrheic calves in the Cryptosporidium spp. group (P<0.001). This increase was also observed in the Cryptosporidium spp. group at 72 h (P<0.001). A positive and moderate correlation was observed between Procalcitonin and TNF-α (r = 0.603, P<0.001). As a result, it was concluded that the Procalcitonin value, along with other tests, could be used as a biomarker to determine the prognosis of the disease in diarrheic calves, regardless of the etiological agent. This study was evaluated as an original study in which cytokines and acute phase proteins were investigated before and after treatment, with diarrhea divided into subgroups.

Human activities and climate change have negatively affected the world's oceans, leading to a decline of 30 to 60 % in coastal ecosystems' biodiversity and habitats. The projected increase in the human population to 9.7 billion by 2050 raises concerns about the sustainability of marine ecosystem conservation and exploitation. Marine turtles, as sentinel species, accumulate contaminants, including trace elements, due to their extensive migration and long-life span. However, there is a lack of data on the degree of contamination and their effects on marine turtles' health. This study focuses on assessing in-situ inorganic contamination in juvenile green sea turtles from La Réunion Island and its short-term impact on individual health, using conventional biomarkers and proteomics. The goals include examining contamination patterns in different tissues and identifying potential new biomarkers for long-term monitoring and conservation efforts. The study identified differential metal contamination between blood and scute samples, which could help illuminate temporal exposure to trace elements in turtle individuals. We also found that some conventional biomarkers were related to trace element exposure, while the proteome responded differently to various contaminant mixtures. Immune processes, cellular organization, and metabolism were impacted, indicating that contaminant mixtures in the wild would have an effect on turtle's health. Fifteen biomarker candidates associated with strong molecular responses of sea turtle to trace element contamination are proposed for future long-term monitoring. The findings emphasize the importance of using proteomic approaches to detect subtle physiological responses to contaminants in the wild and support the need for non-targeted analysis of trace elements in the biomonitoring of sea turtle health.

In this study, we examined the effects of experimental intraperitoneal infection with haemotropic Mycoplasma ovis (0.5 mL of blood containing 80% parasitaemia) on selected serum biomarkers and cellular pathology in mice. After infection, M. ovis cells appeared in the blood films within one week. A dose-dependent peak of parasitemia was observed during the 3rd-week post-infection (pi), with a significant decrease in mean PCV between treatment versus control group at week 3 (t 14 = -3.693, P < 0.02), week 5 (t 14 = -2.096, P = 0.055), and week 7 (t 14 = -4.329, P = 0.001). There was a significantly (t 8 = -2.330, P = 0.048) lower serum oestrogen in treatment (10.38 ± 5.07) than control (17.43 ± 4.48), while serum progesterone was significantly (t 8 = 5.415, P = 0.001) increased in treatment (27.37 ± 2.17) than control (15.92 ± 4.20). Serum haptoglobin was significantly (t 8 = 8.525, P < 0.01) lower in treatment (8.72 ± 1.49) than control (18.16 ± 1.98) while the SAA was significantly (t 8 = 3.362, P = 0.01) higher in treatment (16.79 ± 2.71) than control (11.59 ± 2.15). Prominent lesions observed in the ovary include degeneration, necrosis, vacuolation, and hypertrophy of the lutein cells in corpora lutea. In the lymph nodes, diffused cellular hyperplasia of the lymphoid tissue in the cortex. In the liver, degeneration and necrosis accompanied by leucocytic cellular infiltration and Kupffer cell proliferation within the sinusoids. There were diffused leucocytic infiltrations and proliferative lesions in the glomerulus of the kidneys. The disturbance in progesterone and ovarian pathology highlights the potential role of haemotropic M. ovis in reproductive disorders. The observed changes in biomarkers and cellular reactions following M. ovis infection in the mouse may be further advanced in sheep and goats.

The objective of this study was to investigate the interactive effect of dietary cation-anion difference (DCAD) and dietary buffer supply on DMI, ruminal fermentation, milk and milk component yields, and gastrointestinal tract (GIT) permeability in lactating dairy cattle exposed to mild heat stress. Sixteen lactating Holstein cows, including 8 ruminally cannulated primiparous (80 ± 19.2 DIM) and 8 non-cannulated multiparous (136 ± 38.8 DIM) cows, were housed in a tie-stall barn programmed to maintain a temperature-humidity index (THI) between 68 and 72 from 0600 h to 1600 h followed by natural night cooling. The experimental design was a replicated 4 × 4 Latin rectangle (21-d periods) with a 2 × 2 factorial treatment arrangement. Diets contained a low DCAD (LD; 17.5 mEq/100g of DM) or high DCAD (HD; 39.6 mEq/100g of DM) adjusted using NH4Cl and Na-acetate, with low (LB; 0% CaMg(CO3)2) or high buffer (HB; 1% CaMg(CO3)2). In addition to measurement of feed intake, ruminal fermentation, and milk and milk component yields, a ruminal dose of Cr-EDTA and an equimolar abomasal dose of Co-EDTA were used to evaluate total and post-ruminal gastrointestinal tract permeability, respectively. Treatments had no effect on DMI, ruminal short-chain fatty acid concentrations, or ruminal pH. Feeding HD improved blood acid-base balance, increased urine volume by 4 ± 1.5 kg/d, and increased milk fat by 0.14 ± 0.044 percentage units and milk fat yield by 36.5 ± 16.71 g/d. HB reduced milk fat percentage by 0.11 ± 0.044 percentage units and had no effect on milk fat yield. The HB treatments reduced urinary excretion of Co by 27% and tended to reduce urinary Cr excretion by 10%. Across all treatments, 72% of the Cr recovery was represented by Co suggesting that much of the permeability responses were post-ruminal during mild heat stress. In conclusion, increasing DCAD through greater Na supply during mild heat stress improved blood acid-base balance and may increase milk fat yield. Dietary inclusion of CaMg(CO3)2 improved post-ruminal GIT barrier function despite a lack of low ruminal pH. As there appeared to be a limited interactive effect between DCAD and buffer, increased DCAD and provision of buffer seem to independently influence physiological and performance responses in lactating dairy cows exposed to mild heat with night cooling.

Urbanization processes modulate the immunological challenges faced by animals. Urban habitat transformations reshape pathogen diversity and abundance, while high population density-common in urban exploiter species-promotes disease transmission. Responses to urbanization may include adaptive adjustments of constitutive innate immune defenses (e.g. complement system and natural antibodies [NAbs]), which serve as first-line protection against infections. Here, we investigated associations of habitat urbanization and host population density with complement and NAbs in an urban bird, the feral pigeon Columba livia domestica. To do so, we employed the hemolysis-hemagglutination assay to analyze nearly 200 plasma samples collected across urbanization and pigeon population density gradients in five major cities in Poland. We found a negative association between urbanization score and hemagglutination (i.e. NAbs activity), but not hemolysis (i.e. complement activity), indicating either immunosuppression or adaptive downregulation of this immune defense in highly transformed urban landscape. Population density was not significantly related to either immune parameter, providing no evidence for density-dependent modulation of immune defenses. At the same time, there was a negative association of hemolysis with condition (scaled mass index), suggesting resource allocation trade-offs or contrasting effects of the urban environment on immune defenses and body condition. The results demonstrate that habitat structure can be an important factor shaping the immune defenses of the feral pigeon, although these associations were not mediated by variation in population density. Our study highlights the complexity of the links between immune defenses in wildlife and urbanization and reinforces the need for comprehensive ecoimmunological studies on urban animals.

To mitigate the use of antibiotics for many of the multifactorial diseases seen in pigs, horses and cattle, new diagnostic tools are needed. Acute phase protein (APP) measurements can, in humans, be used to guide antibiotic treatment initiation, evaluate treatment efficacy, and make a prognosis. The aim of this review is to collect evidence on the clinical functionality of APP measurements as a tool to guide antibiotic treatment in pigs, horses, and cattle. Literature was retrieved using Medline, CAB Abstracts and Google Scholar. The acute phase response has been investigated for a plethora of diseases and clinical signs and the major acute phase proteins are elevated in diseased compared to healthy animals. Few studies correlated acute phase response with aetiology, antibiotic treatment efficacy, prognosis, or severity of disease. The existing research does not support that APP can be used to guide antibiotic treatment, but the reported studies indicate that C-reactive protein (CRP) might be able to differentiate between bacterial and non-bacterial causes of disease in pigs. Serum amyloid A (SAA) might reflect underlying aetiology in horses and infectious or non-infectious cases of mastitis in cows.

Despite unprecedented survival in patients with glioblastoma (GB), the aggressive primary brain cancer remains largely incurable and its mechanisms of treatment resistance have gained particular attention. The cytokine interleukin 6 (IL-6) and its receptor weave through the hallmarks of malignant gliomas and may represent a key vulnerability to GB. Known for activating the STAT3 pathway in autocrine fashion, IL-6 is amplified in GB and has been recognized as a negative biomarker for GB prognosis, rendering it a putative target of novel GB therapies. While it has been recognized as a biologically active component of GB for three decades only with concurrent advances in understanding of complementary immunotherapy has the concept of targeting IL-6 for a human clinical trial gained scientific footing.

MicroRNAs (miR) are a group of small, non-coding RNAs of 17-25 nucleotides that regulate gene expression at the post-transcriptional level. Dysregulation of miRNA expression or function may contribute to abnormal gene expression and signaling pathways, leading to disease pathology. Lagovirus europaeus (L. europaeus) causes severe disease in rabbits called rabbit hemorrhagic disease (RHD). The symptoms of liver, lung, kidney, and spleen degeneration observed during RHD are similar to those of acute liver failure (ALF) and multi-organ failure (MOF) in humans. In this study, we assessed the expression of miRs and their target genes involved in the innate immune and inflammatory response. Also, we assessed their potential impact on pathways in L. europaeus infection-two genotypes (GI.1 and GI.2)-in the liver, lungs, kidneys, and spleen. The expression of miRs and target genes was determined using quantitative real-time PCR (qPCR). We assessed the expression of miR-155 (MyD88, TAB2, p65, NLRP3), miR-146a (IRAK1, TRAF6), miR-223 (TLR4, IKKα, NLRP3), and miR-125b (MyD88). We also examined biomarkers of inflammation: IL-1β, IL-6, TNF-α, and IL-18 in four tissues at the mRNA level. Our study shows that the main regulators of the innate immune and inflammatory response in L. europaeus/GI.1 and GI.2 infection, as well as RHD, are miR-155, miR-223, and miR-146a. During infection with L. europaeus/RHD, miR-155 has both pro- and anti-inflammatory effects in the liver and anti-inflammatory effects in the kidneys and spleen; miR-146a has anti-inflammatory effects in the liver, lungs and kidneys; miR-223 has anti-inflammatory effects in all tissues; however, miR-125b has anti-inflammatory effects only in the liver. In each case, such an effect may be a determinant of the pathogenesis of RHD. Our research shows that miRs may regulate three innate immune and inflammatory response pathways in L. europaeus infection. However, the result of this regulation may be influenced by the tissue microenvironment. Our research shows that infection of rabbits with L. europaeus/GI.1 and GI.2 genotypes causes an overexpression of two critical acute phase cytokines: IL-6 in all examined tissues and TNF-α (in the liver, lungs, and spleen). IL-1β was highly expressed only in the lungs after L. europaeus infection. These facts indicate a strong and rapid involvement of the local innate immune and inflammatory response in L. europaeus infection-two genotypes (GI.1 and GI.2)-and in the pathogenesis of RHD. Profile of biomarkers of inflammation in rabbits infected with L. europaeus/GI.1 and GI.2 genotypes are similar regarding the nature of changes but are different for individual tissues. Therefore, we propose three inflammation profiles for L. europaeus infection for both GI.1 and GI.2 genotypes (pulmonary, renal, liver, and spleen).

A dysregulated inflammatory response contributes to the occurrence of disorders in cows during the transition period from pregnancy to lactation. However, a detailed characterization of clinically healthy cows that exhibit an enhanced inflammatory response during this critical period remains incomplete. In this experiment, a total of 99 individual transition dairy cows and 109 observations (18 cows monitored in 2 consecutive lactations), submitted to similar transition management were involved to evaluate the relationship between elevated an inflammatory response and metabolic and oxidative status, as well as transition outcomes. Blood was taken at -7, 3, 6, 9, and 21 DIM, and concentrations of metabolic parameters (glucose, β-hydroxybutyric acid, nonesterified fatty acids [NEFA], insulin, IGF-1, and fructosamine) were analyzed. Additionally, oxidative parameters (proportion of oxidized glutathione to total glutathione in red blood cells, the activity of glutathione peroxidase [GPx] and superoxide dismutase, concentrations of malondialdehyde, and oxygen radical absorbance capacity) and acute phase proteins (APP) including haptoglobin (Hp), serum amyloid A (SAA) and albumin-to-globulin ratio (A:G) were determined in the blood at 21 DIM. The 3 APP parameters were used to group clinically healthy cows into 2 categories through k-medoids clustering (i.e., a group showing an acute phase response, APR; n = 39) and a group not showing such a response (i.e., non-APR; n = 50). Diseased cases (n = 20) were handled in a separate group. Lower SAA and Hp concentrations as well as higher A:G were observed in the non-APR group, although for Hp, differences were observed from the APR group and not from the diseased group. Only 1 of the 5 oxidative parameters differed between the groups, with the non-APR group exhibiting lower GPx activity compared with the diseased group. The non-APR group showed the highest IGF-1 levels among the 3 groups and and lower NEFA concentrations compared with the diseased groups. Cows in the diseased group also showed reduced dry matter intake and milk yield compared with clinically healthy cows, regardless of their inflammatory status. Moreover, the APR group exhibited temporarily lower activity levels compared with the non-APR group. These findings highlight that cows with a lower inflammatory status after 21 DIM exhibited better metabolic health characteristics and productive performance, as well as activity levels. Nevertheless, the detrimental effects of a higher inflammatory status in the absence of clinical symptoms are still relatively limited.

Infectious bronchitis (IB) is an important disease of poultry, and vaccination is the best method of preventing IB in the poultry industry worldwide.

This study was designed to evaluate cytokine and acute-phase protein (APP) responses and their correlations with antibody titres following vaccination regimes against IB in the broiler.

Broilers were vaccinated with H120 and 1/96 vaccine strains, and MIX (H120 + 1/96) vaccine strains on Days 0 and 14. Heterophils/lymphocyte (H/L) ratio, APPs including chicken serum amyloid A (SAA), chicken pentraxin 3 (chPTX3), chicken interleukin 1β (IL-1β), chicken interleukin 6 (IL-6) levels and antibody titres were measured.

An increase in the H/L ratio, SAA, chPTX3, IL-1β and IL-6 levels in vaccinated groups was observed 1 day after the first (highest rates) and second (lower levels) vaccination up to 3 days in three different patterns and then started to decrease. The results showed an immediate, short-lived response and moderate increases in all criteria. Changing patterns of APPs were different but in similar pattern after the first and second immunization in vaccinated groups. A positive correlation between all criteria values on Days 1 and 15 with antibody titres on Day 28 may indicate agonistic cross-regulation.

Different types of IB vaccines could induce different patterns of APPs responses, which can be used to evaluate immune response outcomes in vaccine design, development and administration. The IL-6 with the highest increase can be a sensitive parameter and chPTX3 with the high increase could be an important criterion.

Cutaneous hypersensitivity reactions (CHRs) are complex inflammatory skin disorders that affect humans and dogs. This study examined the inflammatory and immune responses leading to skin damage, inflammation, and irritation by investigating gene expression through quantitative PCR (qPCR) and protein localization through the immunohistochemistry (IHC) of specific receptors and molecules involved in CHRs. Formalin-fixed paraffin-embedded (FFPE) samples from canine CHR skin (n = 20) and healthy dog skin (n = 3) were analyzed for expression levels of eight genes, including members of the pattern recognition receptor (PRR) family, CD209 and CLEC4G, the Regakine-1-like chemokine, and acute phase proteins (APPs), LBP-like and Hp-like genes. Additionally, we examined the local involvement of IL-6, Janus Kinase 1 (JAK1), and the signal transducer activator of transcription 3 (STAT3) in the CHR cases. The study demonstrated statistically significant increases in the expression levels of CD209, Hp-like (p < 0.01), LBP-like, Regakine-1-like, and CLEC4G (p < 0.05) genes in CHRs compared to healthy controls. Conversely, IL-6, JAK1, and STAT3 showed no significant difference between the two groups (p > 0.05). Protein analysis revealed JAK1 and STAT3 expression in CHR hyperplastic epithelial cells, dermal fibroblasts, and endothelial cells of small capillaries, indicating a possible involvement in the JAK/STAT pathway in local inflammatory response regulation. Our findings suggest that the skin plays a role in the development of CHRs.

The complement system plays a crucial role in orchestrating the activation and regulation of inflammation within the human immune system. Three distinct activation pathways-classical, lectin, and alternative-converge to form the common lytic pathway, culminating in the formation of the membrane-attacking complex that disrupts the structure of pathogens. Dysregulated complement system activity can lead to tissue damage, autoimmune diseases, or immune deficiencies. In this study, the antimicrobial activity of human serum was investigated by using a bioluminescent microbe probe, Escherichia coli (pEGFPluxABCDEamp). This probe has previously been used to determine the antimicrobial activity of complement system and the polymorphonuclear neutrophils. In this study, blocking antibodies against key serum activators and components, including IgG, complement component 1q, factor B, and properdin, were utilized. The influence of body temperature and acute phase proteins, such as C reactive protein (CRP) and serum amyloid alpha (SAA), on the complement system was also examined. The study reveals the critical factors influencing complement system activity and pathway function. Alongside crucial factors like C1q and IgG, alternative pathway components factor B and properdin played pivotal roles. Results indicated that the alternative pathway accounted for approximately one third of the overall serum antimicrobial activity, and blocking this pathway disrupted the entire complement system. Contrary to expectations, elevated body temperature during inflammation did not enhance the antimicrobial activity of human serum. CRP demonstrated complement activation properties, but at higher physiological concentrations, it exhibited antagonistic tendencies, dampening the response. On the other hand, SAA enhanced the serum's activity. Overall, this study sheds a light on the critical factors affecting both complement system activity and pathway functionality, emphasizing the importance of a balanced immune response.

Immunotherapy, specifically immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment. However, it can also cause immune-related adverse events (irAEs). This study aimed to develop a clinically practical animal model of irAEs using BALB/c mice.

Subcutaneous tumors of mouse breast cancer 4T1 cells were generated in inbred BALB/c mice. The mice were treated with programmed death-1 (PD-1) and cytotoxic t-lymphocyte antigen 4 (CTLA-4) inhibitors once every 3 days for five consecutive administration cycles. Changes in tumor volume and body weight were recorded. Lung computed tomography (CT) scans were conducted. The liver, lungs, heart, and colon tissues of the mice were stained with hematoxylin-eosin (H&E) staining to observe inflammatory infiltration and were scored. Serum samples were collected, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of ferritin, glutamic-pyruvic transaminase (ALT), tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), and interleukin-6 (IL-6). Mouse liver and lung cell suspensions were prepared, and changes in macrophages, T cells, myeloid-derived suppressor cells (MDSCs), and regulatory (Treg) cells were detected by flow cytometry.

Mice treated with PD-1 and CTLA-4 inhibitors showed significant reductions in tumor volume and body weight. The tissue inflammatory scores in the experimental group were significantly higher than those in the control group. Lung CT scans of mice in the experimental group showed obvious inflammatory spots. Serum levels of ferritin, IL-6, TNF-α, IFN-γ, and ALT were significantly elevated in the experimental group. Flow cytometry analysis revealed a substantial increase in CD3+T cells, Treg cells, and macrophages in the liver and lung tissues of mice in the experimental group compared with the control group, and the change trend of MDSCs was opposite.

The irAE-related animal model was successfully established in BALB/c mice using a combination of PD-1 and CTLA-4 inhibitors through multiple administrations with clinical translational value and practical. This model offers valuable insights into irAE mechanisms for further investigation.

The first year of life is a period of rapid immune development that can impact health trajectories and the risk of developing respiratory-related diseases, such as asthma, recurrent infections, and eczema. However, the biology underlying subsequent disease development remains unknown.

Using weighted gene correlation network analysis (WGCNA), we derived modules of highly correlated immune-related proteins in plasma samples from children at age 1 year (N=294) from the Vitamin D Antenatal Asthma Reduction Trial (VDAART). We applied regression analyses to assess relationships between protein modules and development of childhood respiratory diseases up to age 6 years. We then characterized genomic, environmental, and metabolomic factors associated with modules.

WGCNA identified four protein modules at age 1 year associated with incidence of childhood asthma and/or recurrent wheeze (Padj range: 0.02-0.03), respiratory infections (Padj range: 6.3×10-9-2.9×10-6), and eczema (Padj=0.01) by age 6 years; three modules were associated with at least one environmental exposure (Padj range: 2.8×10-10-0.03) and disrupted metabolomic pathway(s) (Padj range: 2.8×10-6-0.04). No genome-wide SNPs were identified as significant genetic risk factors for any protein module. Relationships between protein modules with clinical, environmental, and 'omic factors were temporally sensitive and could not be recapitulated in protein profiles at age 6 years.

These findings suggested protein profiles as early as age 1 year predicted development of respiratory-related diseases through age 6 and were associated with changes in pathways related to amino acid and energy metabolism. These may inform new strategies to identify vulnerable individuals based on immune protein profiling.

Using proteomics and complexome profiling, we evaluated in a year-long study longitudinal variations in the plasma proteome of kidney failure patients, prior to and after a kidney transplantation. The post-transplant period was complicated by bacterial infections, resulting in dramatic changes in the proteome, attributed to an acute phase response (APR). As positive acute phase proteins (APPs), being elevated upon inflammation, we observed the well-described C-reactive protein and Serum Amyloid A (SAA), but also Fibrinogen, Haptoglobin, Leucine-rich alpha-2-glycoprotein, Lipopolysaccharide-binding protein, Alpha-1-antitrypsin, Alpha-1-antichymotrypsin, S100, and CD14. As negative APPs, being downregulated upon inflammation, we identified the well-documented Serotransferrin and Transthyretin, but added Kallistatin, Heparin cofactor 2, and interalpha-trypsin inhibitor heavy chain H1 and H2 (ITIH1, ITIH2). For the patient with the most severe APR, we performed plasma complexome profiling by SEC-LC-MS on all longitudinal samples. We observed that several plasma proteins displaying alike concentration patterns coelute and form macromolecular complexes. By complexome profiling, we expose how SAA1 and SAA2 become incorporated into high-density lipid particles, replacing largely Apolipoprotein (APO)A1 and APOA4. Overall, our data highlight that the combination of in-depth longitudinal plasma proteome and complexome profiling can shed further light on correlated variations in the abundance of several plasma proteins upon inflammatory events.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects the joints of the human body and is projected to have a prevalence age-standardized rate of 1.5 million new cases worldwide by 2030. Several conventional and non-conventional preventive and therapeutic interventions have been suggested but they have their side effects including nausea, abdominal pain, liver damage, ulcers, heightened blood pressure, coagulation, and bleeding. Interestingly, several food-derived peptides (FDPs) from both plant and animal sources are increasingly gaining a reputation for their potential in the management or therapy of RA with little or no side effects. In this review, the concept of inflammation, its major types (acute and chronic), and RA identified as a chronic type were discussed based on its pathogenesis and pathophysiology. The conventional treatment options for RA were briefly outlined as the backdrop of introducing the FDPs that potentiate therapeutic effects in the management of RA.

This study investigates the intricate interplay between environmental pollutants and exosomes, shedding light on a novel paradigm in environmental health and disease. Cellular stress, induced by environmental toxicants or disease, significantly impacts the production and composition of exosomes, crucial mediators of intercellular communication. The heat shock response (HSR) and unfolded protein response (UPR) pathways, activated during cellular stress, profoundly influence exosome generation, cargo sorting, and function, shaping intercellular communication and stress responses. Environmental pollutants, particularly lipophilic ones, directly interact with exosome lipid bilayers, potentially affecting membrane stability, release, and cellular uptake. The study reveals that exposure to environmental contaminants induces significant changes in exosomal proteins, miRNAs, and lipids, impacting cellular function and health. Understanding the impact of environmental pollutants on exosomal cargo holds promise for biomarkers of exposure, enabling non-invasive sample collection and real-time insights into ongoing cellular responses. This research explores the potential of exosomal biomarkers for early detection of health effects, assessing treatment efficacy, and population-wide screening. Overcoming challenges requires advanced isolation techniques, standardized protocols, and machine learning for data analysis. Integration with omics technologies enhances comprehensive molecular analysis, offering a holistic understanding of the complex regulatory network influenced by environmental pollutants. The study underscores the capability of exosomes in circulation as promising biomarkers for assessing environmental exposure and systemic health effects, contributing to advancements in environmental health research and disease prevention.

Background: Burns represent a serious health problem, associated with multiple-organ failure, prolonged hospitalization, septic complications, and increased rate of mortality. The main aim of our study was to evaluate the levels of various circulating molecules in children with severe burns (more than 25% TBSA), in three different moments: 48 h, day 10, and day 21 post-burn. Materials and Methods: This study included 32 children with burns produced by flame, hot liquid, and electric arc and 21 controls. Serum plasminogen activator inhibitor-1 (PAI-1), α 1-acid glycoprotein (AGP), C-reactive protein (CRP), and platelet factor 4 (PF4) were detected using the Multiplex technique. Several parameters, such as fibrinogen, leucocyte count, thrombocyte count, triiodothyronine, thyroxine, and thyroid-stimulating hormone were also determined for each patient during hospitalization. Results: Significant statistical differences were obtained for CRP, AGP, and PF4 compared to the control group, in different moments of measurements. Negative correlations between CRP, AGP, and PF4 serum levels and burned body surface, and also the hospitalization period, were observed. Discussions: CRP levels increased in the first 10 days after burn trauma and then decreased after day 21. Serum PAI-1 levels were higher immediately after the burn and started decreasing only after day 10 post-burn. AGP had elevated levels 48 h after the burn, then decreased at 7-10 days afterwards, and once again increased levels after 21 days. PF4 serum levels increased after day 10 since the burning event. Conclusions: Serum CRP, AGP, PAI-1, and PF4 seem to be promising molecules in monitoring patients with a burn within the first 21 days.

Through technological innovations, patient cohorts can be examined from multiple views with high-dimensional, multiscale biomedical data to classify clinical phenotypes and predict outcomes. Here, we aim to present our approach for analyzing multimodal data using unsupervised and supervised sparse linear methods in a COVID-19 patient cohort. This prospective cohort study of 149 adult patients was conducted in a tertiary care academic center. First, we used sparse canonical correlation analysis (CCA) to identify and quantify relationships across different data modalities, including viral genome sequencing, imaging, clinical data, and laboratory results. Then, we used cooperative learning to predict the clinical outcome of COVID-19 patients: Intensive care unit admission. We show that serum biomarkers representing severe disease and acute phase response correlate with original and wavelet radiomics features in the LLL frequency channel (cor(Xu1, Zv1) = 0.596, p value < 0.001). Among radiomics features, histogram-based first-order features reporting the skewness, kurtosis, and uniformity have the lowest negative, whereas entropy-related features have the highest positive coefficients. Moreover, unsupervised analysis of clinical data and laboratory results gives insights into distinct clinical phenotypes. Leveraging the availability of global viral genome databases, we demonstrate that the Word2Vec natural language processing model can be used for viral genome encoding. It not only separates major SARS-CoV-2 variants but also allows the preservation of phylogenetic relationships among them. Our quadruple model using Word2Vec encoding achieves better prediction results in the supervised task. The model yields area under the curve (AUC) and accuracy values of 0.87 and 0.77, respectively. Our study illustrates that sparse CCA analysis and cooperative learning are powerful techniques for handling high-dimensional, multimodal data to investigate multivariate associations in unsupervised and supervised tasks.