Search Results (35)

Objective: Polycystic ovary syndrome (PCOS) is a prevalent metabolic disorder with an increased risk for cardiovascular disease (CVD) that is enhanced by obesity. This study sought to determine whether a panel of cardiovascular risk proteins (CVRPs) would be dysregulated in overweight/obese PCOS patients, highlighting potential biomarkers for CVD in PCOS. Methods: In this exploratory cross-sectional study, plasma levels of 54 CVRPs were analyzed in women with PCOS (n = 147) and controls (n = 97). CVRPs were measured using the SOMAscan proteomic platform (version 3.1), with significant proteins identified through linear models, regression analysis, and receiver operating characteristic (ROC) analysis. Analysis on BMI-matched subsets of the cohort were undertaken. Functional enrichment and protein–protein interaction analyses elucidated the pathways involved. Results: Eleven CVRPs were dysregulated in PCOS (whole set, without matching for body mass index (BMI) or insulin resistance (IR)): leptin, Interleukin-1 receptor antagonist protein (IL-1Ra), polymeric immunoglobulin receptor (PIGR), interleukin-18 receptor (IL-18Ra), C-C motif chemokine 3 (MIP-1a), and angiopoietin-1 (ANGPT1) were upregulated whilst advanced glycosylation end product-specific receptor, soluble (sRAGE), bone morphogenetic protein 6 (BMP6); growth/differentiation factor 2 (GDF2), superoxide dismutase [Mn] mitochondrial (MnSOD), and SLAM family member 5 (SLAF5) were downregulated versus the controls. In BMI-matched (overweight/obese, BMI ≥ 26 kg/m²) subset analysis, six CVRPs were common to the whole set: ANGPT1 and IL-1Ra were upregulated; and sRAGE, BMP6, GDF2, and Mn-SOD were downregulated. In addition, lymphotactin (XCL1) was upregulated and placenta growth factor (PIGF), alpha-L-iduronidase (IDUA), angiopoietin-1 receptor, and soluble (sTie-2) and macrophage metalloelastase (MMP12) were downregulated. A subset analysis of BMI-matched plus insulin resistance (IR)-matched women revealed only upregulation of tissue factor (TF) and renin in PCOS, potentially serving as biomarkers for cardiovascular risk in overweight/obese women with PCOS. Conclusions: A combination of upregulated obesity-related CVRPs (ANGPT1/IL/1Ra/XCL1) and downregulated cardioprotective proteins (sRAGE/BMP6/Mn-SOD/GDF2) in overweight/obese PCOS women may contribute to the increased risk for CVD. TF and renin upregulation observed in the BMI- and IR-matched limited sample PCOS subgroup indicates their potential risk of CVD. Full article

Background/Objectives: Breast cancer in women is the most commonly diagnosed and most malignant tumor. Although luminal A breast cancer (LumA) has a relatively better prognosis, it still has a persistent pattern of recurrence. Ganoderma lucidum (Curtis) P. Karst. is a kind of traditional Chinese medicine and has antitumor effects. In this study, we aimed to identify the genes relevant to prognosis, find novel targets, and investigate the function of the bioactive protein from G. lucidum, called FIP-glu, in improving prognosis. Methods: Gene expression data and clinical information of LumA breast cancer patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Using bioinformatics methods, a predictive risk model was constructed to predict the prognosis for each patient. The cell counting kit-8 (CCK8) and clone formation assays were used to validate gene function. The ability of FIP-glu to regulate RNA levels of risk genes was validated. Results: Six risk genes (slit-roundabout GTPase-activating protein 2 (SRGAP2), solute carrier family 35 member 2 (SLC35A2), sequence similarity 114 member A1 (FAM114A1), tumor protein P53-inducible protein 11 (TP53I11), transmembrane protein 63C (TMEM63C), and polymeric immunoglobulin receptor (PIGR)) were identified, and a prognostic model was constructed. The prognosis was worse in the high-risk group and better in the low-risk group. The receiver operating characteristic (ROC) curve confirmed the model’s accuracy. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the differentially expressed genes (DEGs) between the high- and low-risk groups were significantly enriched in the immune responses. TMEM63C could promote tumor viability, growth, and proliferation in vitro. FIP-glu significantly regulated these risk genes, and attenuated the promoting effect of TMEM63C in breast cancer cells. Conclusions: SRGAP2, SLC35A2, FAM114A1, TP53I11, TMEM63C, and PIGR were identified as the potential risk genes for predicting the prognosis of patients. TMEM63C could be a potential novel therapeutic target. Moreover, FIP-glu was a promising drug for improving the prognosis of LumA breast cancer. Full article

Supernumerary teats (SNTs) or nipples often emerge around the mammary line. This study performed a genome-wide selective sweep analysis (GWS) at the copy number variant (CNV) level using two selected signal calculation methods (V_ST and F_ST) to identify candidate genes associated with SNTs in goats. A total of 12,310 CNVs were identified from 37 animals and 123 CNVs, with the top 1% V_ST values including 84 candidate genes (CDGs). Of these CDGs, minichromosome maintenance complex component 3, ectodysplasin A receptor associated via death domain, and cullin 5 demonstrated functions closely related to mammary gland development. In addition, 123 CNVs with the top 1% F_ST values were annotated to 97 CDGs. 5-Hydroxytryptamine receptor 2A, CCAAT/enhancer-binding protein alpha, and the polymeric immunoglobulin receptor affect colostrum secretion through multiple signaling pathways. Two genes, namely, RNA-binding motif protein 46 and β-1,3-galactosyltransferase 5, showed a close relation to mammary gland development. Six CNVs were identified and annotated to five genes by intersecting the top 1% of candidate CNVs with both parameters. These genes include LOC102185621, LOC102190481, and UDP-glucose pyrophosphorylase 2, which potentially affect the occurrence of BC through multiple biological processes, such as cell detoxification, glycogen synthesis, and phospholipid metabolism. In conclusion, we discovered numerous genes related to mammary development and breast cancer (BC) through a GWS, which suggests the mechanism of SNTs in goats and a certain association between mammary cancer and SNTs. Full article

Background/Objectives: Survival prospects following SARS-CoV-2 infection may extend beyond the acute phase, influenced by various factors including age, health conditions, and infection severity; however, this topic has not been studied in detail. Therefore, within this study, the mortality risk post-acute COVID-19 in the CRIT-COV-U cohort was investigated. Methods: Survival data from 651 patients that survived an acute phase of COVID-19 were retrieved and the association between urinary peptides and future death was assessed. Data spanning until December 2023 were collected from six countries, comparing mortality trends with age- and sex-matched COVID-19-negative controls. A death prediction classifier was developed and validated using pre-existing urinary peptidomic datasets. Results: Notably, 13.98% of post-COVID-19 patients succumbed during the follow-up, with mortality rates significantly higher than COVID-19-negative controls, particularly evident in younger individuals (<65 years). These data for the first time demonstrate that SARS-CoV-2 infection highly significantly increases the risk of mortality not only during the acute phase of the disease but also beyond for a period of about one year. In our study, we were further able to identify 201 urinary peptides linked to mortality. These peptides are fragments of albumin, alpha-2-HS-glycoprotein, apolipoprotein A-I, beta-2-microglobulin, CD99 antigen, various collagens, fibrinogen alpha, polymeric immunoglobulin receptor, sodium/potassium-transporting ATPase, and uromodulin and were integrated these into a predictive classifier (DP201). Higher DP201 scores, alongside age and BMI, significantly predicted death. Conclusions: The peptide-based classifier demonstrated significant predictive value for mortality in post-acute COVID-19 patients, highlighting the utility of urinary peptides in prognosticating post-acute COVID-19 mortality, offering insights for targeted interventions. By utilizing these defined biomarkers in the clinic, risk stratification, monitoring, and personalized interventions can be significantly improved. Our data also suggest that mortality should be considered as one possible symptom or a consequence of post-acute sequelae of SARS-CoV-2 infection, a fact that is currently overlooked. Full article

Chronic Lymphocytic Leukemia (CLL) is the most common B-cell malignancy in the Western world, characterized by frequent relapses despite temporary remissions. Our study integrated publicly available proteomic, transcriptomic, and patient survival datasets to identify key differences between healthy and CLL samples. We exposed approximately 1000 proteins that differentiate healthy from cancerous cells, with 608 upregulated and 415 downregulated in CLL cases. Notable upregulated proteins include YEATS2 (an epigenetic regulator), PIGR (Polymeric immunoglobulin receptor), and SNRPA (a splicing factor), which may serve as prognostic biomarkers for this disease. Key pathways implicated in CLL progression involve RNA processing, stress resistance, and immune response deficits. Furthermore, we identified three existing drugs—Bosutinib, Vorinostat, and Panobinostat—for potential further investigation in drug repurposing in CLL. We also found limited correlation between transcriptomic and proteomic data, emphasizing the importance of proteomics in understanding gene expression regulation mechanisms. This generally known disparity highlights once again that mRNA levels do not accurately predict protein abundance due to many regulatory factors, such as protein degradation, post-transcriptional modifications, and differing rates of translation. These results demonstrate the value of integrating omics data to uncover deregulated proteins and pathways in cancer and suggest new therapeutic avenues for CLL. Full article

A T-cell-independent (TI) pathway activated by microbiota results in the generation of low-affinity homeostatic IgA with a critical role in intestinal homeostasis. Moderate aerobic exercise (MAE) provides a beneficial impact on intestinal immunity, but the action of MAE on TI-IgA generation under senescence conditions is unknown. This study aimed to determine the effects of long-term MAE on TI-IgA production in young (3 month old) BALB/c mice exercised until adulthood (6 months) or aging (24 months). Lamina propria (LP) from the small intestine was obtained to determine B cell and plasma cell sub-populations by flow cytometry and molecular factors related to class switch recombination [Thymic Stromal Lymphopoietin (TSLP), A Proliferation-Inducing Ligand (APRIL), B Cell Activating Factor (BAFF), inducible nitric oxide synthase (iNOS), and retinal dehydrogenase (RDH)] and the synthesis of IgA [α-chain, interleukin (IL)-6, IL-21, and Growth Factor-β (TGF-β)]; and epithelial cells evaluated IgA transitosis [polymeric immunoglobulin receptor (pIgR), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-4] by the RT-qPCR technique. The results were compared with data obtained from sedentary age-matched mice. Statistical analysis was computed with ANOVA, and p < 0.05 was considered to be a statistically significant difference. Under senescence conditions, MAE promoted the B cell and IgA+ B cells and APRIL, which may improve the intestinal response and ameliorate the inflammatory environment associated presumably with the downmodulation of pro-inflammatory mediators involved in the upmodulation of pIgR expression. Data suggested that MAE improved IgA and downmodulate the cytokine pro-inflammatory expression favoring homeostatic conditions in aging. Full article

BPH is the most prevalent prostatic condition in aging dogs. Nevertheless, clinical diagnosis and management remain inconsistent. This study employed in-solution digestion coupled with nano-liquid chromatography tandem mass spectrometry to assess serum proteome profiling of dogs with BPH and those dogs after castration. Male dogs were divided into two groups; control and BPH groups. In the BPH group, each dog was evaluated at two time points: Day 0 (BF subgroup) and Day 30 after castration (AT subgroup). In the BF subgroup, three proteins were significantly upregulated and associated with dihydrotestosterone: solute carrier family 5 member 5, tyrosine-protein kinase, and FRAT regulator of WNT signaling pathway 1. Additionally, the overexpression of polymeric immunoglobulin receptors in the BF subgroup hints at its potential as a novel protein linked to the BPH development process. Conversely, alpha-1-B glycoprotein (A1BG) displayed significant downregulation in the BF subgroup, suggesting A1BG’s potential as a predictive protein for canine BPH. Finasteride was associated with increased proteins in the AT subgroup, including apolipoprotein C-I, apolipoprotein E, apolipoprotein A-II, TAO kinase 1, DnaJ homolog subfamily C member 16, PH domain and leucine-rich repeat protein phosphatase 1, neuregulin 1, and pseudopodium enriched atypical kinase 1. In conclusion, this pilot study highlighted alterations in various serum proteins in canine BPH, reflecting different pathological changes occurring in this condition. These proteins could be a source of potential non-invasive biomarkers for diagnosing this disease. Full article

Bovine colostrum (BC) and mature bovine milk are highly nutritious. In addition to being consumed by adults, these dairy products are also used as protein ingredients for infant formula. However, the differences in the nutritional composition of BC and mature milk, especially regarding proteins present in trace amounts, have not been comprehensively studied. Furthermore, the distinct proteomic profiles of mature milk derived from the first lactation (Milk-L1) and the second lactation (Milk-L2) are not fully understood. To address these gaps, this study aims to uncover the subtle differences in protein compositions of BC, Milk-L1, and Milk-L2 by proteomics. Compared with BC, anti-microbial proteins β-defensins and bovine hemoglobin subunit were up-regulated in Milk-L1, while Milk-L2 exhibited higher levels of enteric β-defensin, sterol regulatory element binding transcription factor 1, sydecan-2, and cysteine-rich secretory protein 2. Additionally, immune proteins such as vacuolar protein sorting-associated protein 4B, polymeric immunoglobulin receptor (PIGR), and Ig-like domain-containing protein were found at higher levels in Milk-L1 compared with Milk-L2. The study provides a comprehensive understanding of the distinct proteomic profiles of BC, Milk-L1, and Milk-L2, which contributes to the development of protein ingredients for infant formula. Full article

Background and Objectives: Patients with diabetes are more susceptible to upper respiratory tract infections (URTIs) because they are easily infected. Salivary IgA (sali-IgA) levels play a major role in transmitting URTIs. Sali-IgA levels are determined by salivary gland IgA production and polymeric immunoglobulin receptor (poly-IgR) expression. However, it is unknown whether salivary gland IgA production and poly-IgR expression are decreased in patients with diabetes. While exercise is reported to increase or decrease the sali-IgA levels, it is unclear how exercise affects the salivary glands of patients with diabetes. This study aimed to determine the effects of diabetes and voluntary exercise on IgA production and poly-IgR expression in the salivary glands of diabetic rats. Materials and Methods: Ten spontaneously diabetic Otsuka Long–Evans Tokushima Fatty (OLETF) rats (eight-week-old) were divided into two groups of five rats each: a non-exercise group (OLETF-C) and a voluntary wheel-running group (OLETF-E). Five Long–Evans Tokushima Otsuka (LETO) rats without diabetes were bred under the same conditions as the OLETF-C. Sixteen weeks after the study began, the submandibular glands (SGs) were collected and analyzed for IgA and poly-IgR expression levels. Results: IgA concentrations and poly-IgR expression levels in SGs were lower in OLETF-C and OLETF-E than in LETO (p < 0.05). These values did not differ between the OLETF-C and OLETF-E. Conclusions: Diabetes decreases IgA production and poly-IgR expression in the salivary glands of rats. Moreover, voluntary exercise increases sali-IgA levels but does not increase IgA production and poly-IgR expression in the salivary glands of diabetic rats. Increasing IgA production and poly-IgR expression in the salivary glands, which is reduced in diabetes, might require slightly higher-intensity exercise than voluntary exercise under the supervision of a doctor. Full article

The effects of glutamine (Gln) on immunity and intestinal barrier gene expression levels in broilers challenged with Salmonella Enteritidis were evaluated. A total of 400 1-day-old broilers were randomly assigned to four groups, 10 repetition treatments per group with 10 broiler chickens for a 21-day feeding trial. The groups were the normal control group (CON, no infected group, fed with a basal diet); the S. Enteritidis-infected control group (SCC, infected with 2.0 × 10⁴ CFU/mL of S. Enteritidis, fed a basal diet); and the Gln 1 and 2 groups, who were challenged with S. Enteritidis and fed a basal diet plus Gln at 0.5% and 1.0%, respectively. The results show that S. Enteritidis had adverse effects on the average daily feed intake, average daily gain, and the feed conversion ratio of infected broilers compared with those of CON broilers on d 7 (p < 0.05); decreased serum immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) concentrations, and intestinal mucosa Bcl-2 mRNA expression levels (p < 0.05); increased the Lysozyme (LZM, only serum), NO, inducible NO synthase (iNOS) (except at 4 d), and total nitric oxide synthase (TNOS) (except at 4 d) activities in serum and the intestinal mucosa; and increased intestinal mucosa polymeric immunoglobulin receptor (pIgR) (except at 21 d), Avian beta-defensin 5 (AvBD5), AvBD14, Bax, and Bak mRNA expression levels during the experimental period (p < 0.05). Supplementation with Gln improved growth performance; increased serum IgA, IgG, and IgM concentrations and intestinal mucosa Bcl-2 mRNA expression levels (p < 0.05); decreased the LZM (only serum), NO, iNOS (except at 4 d), and TNOS (except at 4 d) activities in serum and the intestinal mucosa; and decreased intestinal mucosa pIgR (except at 21 d), AvBD5, AvBD14, Bax, and Bak mRNA expression levels during the experimental period (p < 0.05). These results suggest that Gln might lessen the inflammatory reaction of the small intestine and enlarge the small bowel mucosa immune and barrier function in broiler chickens challenged with S. Enteritidis. Full article

The IgM and IgT classes were previously identified and characterized in the Antarctic teleost Trematomus bernacchii, a species belonging to the Perciform suborder Notothenoidei. Herein, we characterized the gene encoding the polymeric immunoglobulin receptor (pIgR) in the same species and compared it to the pIgR of multiple teleost species belonging to five perciform suborders, including 11 Antarctic and 1 non-Antarctic (Cottoperca gobio) notothenioid species, the latter living in the less-cold peri-Antarctic sea. Antarctic pIgR genes displayed particularly long introns marked by sites of transposable elements and transcription factors. Furthermore, analysis of T. bernacchii pIgR cDNA unveiled multiple amino acid substitutions unique to the Antarctic species, all introducing adaptive features, including N-glycosylation sequons. Interestingly, C. gobio shared most features with the other perciforms rather than with the cold-adapted relatives. T. bernacchii pIgR transcripts were predominantly expressed in mucosal tissues, as indicated by q-PCR and in situ hybridization analysis. These results suggest that in cold-adapted species, pIgR preserved its fundamental role in mucosal immune defense, although remarkable gene structure modifications occurred. Full article

Cholecystokinin 8 (CCK8) is an entero-octapeptide that participates in crosstalk with components of intestinal immunity via the CCK receptor (CCKR), but its role in modulation of the IgA response is not fully known under physiological conditions. Male eight-week-old BALB/c mice each were intraperitoneally injected once during 7 days with CCK8, devazapide (CCKR1 antagonist), L365,260 (CCKR2 antagonist) or vehicle (sham group). In intestinal lavages, total and secretory IgA (SIgA) were determined by ELISA; in lamina propria, IgA⁺ B lymphocytes and IgA⁺ plasma cells were analyzed by flow cytometry; mRNA levels of polymeric immunoglobulin receptor (pIgR) in epithelial cells and α chain, interleukins (ILs) in lamina propria cells were assessed by qRTPCR. Regarding the sham conditions, IgA⁺ plasma-cell percentage and IL-2, IL-5, IL-10 and transforming growth factor-β (TGF-β) mRNA levels were either increased by CCK8 or decreased by both CCKR antagonists. For IgA/SIgA responses, IL-4/IL-6 mRNA levels were decreased by all drugs and pIgR mRNA was increased by CCK8 and reduced by L365,260. IgA⁺ B cell percentage and α chain mRNA levels were elicited by CCK8 and L365,260. Data suggested a presumable differential role of CCK/CCKR on the IgA-response; outcome of L365,260 on the elicitation of IgA⁺ B cells and α chain mRNA needs further examination. Full article

Chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis (CF) are distinct respiratory diseases that share features such as the obstruction of small airways and disease flare-ups that are called exacerbations and are often caused by infections. Along the airway epithelium, immunoglobulin (Ig) A contributes to first line mucosal protection against inhaled particles and pathogens. Dimeric IgA produced by mucosal plasma cells is transported towards the apical pole of airway epithelial cells by the polymeric Ig receptor (pIgR), where it is released as secretory IgA. Secretory IgA mediates immune exclusion and promotes the clearance of pathogens from the airway surface by inhibiting their adherence to the epithelium. In this review, we summarize the current knowledge regarding alterations of the IgA/pIgR system observed in those major obstructive airway diseases and discuss their implication for disease pathogenesis. Full article

Innate immunity is the only defense system for resistance against infections in crustaceans. In crustaceans, white spot diseases caused by white spot syndrome virus (WSSV) are a serious viral disease with high accumulative mortality after infection. Attachment and entry into cells have been known to be two initial and important steps in viral infection. However, systematic information about the mechanisms related to WSSV infection in crustaceans is still limited. Previous studies have reported that cellular receptors are important in the innate immune system and are responsible for the recognition of foreign microorganisms and in the stimulation of the immune responses during infections. In this review, we summarize the current understanding of the functions of cellular receptors, including Toll, C-type lectin, scavenger receptor, β-integrin, polymeric immunoglobulin receptor, laminin receptor, globular C1q receptor, lipopolysaccharide-and β-1,3-glucan-binding protein, chitin-binding protein, Ras-associated binding, and Down syndrome cell adhesion molecule in the innate immune defense of crustaceans, especially shrimp and crabs, in response to WSSV infection. The results of this study provide information on the interaction between viruses and hosts during infections, which is important in the development of preventative strategies and antiviral targets in cultured aquatic animals. Full article

Immunoglobulin G (IgG) is currently the most studied immunoglobin class and is frequently used in antibody therapeutics in which its beneficial effector functions are exploited. IgG is composed of two heavy chains and two light chains, forming the basic antibody monomeric unit. In contrast, immunoglobulin A (IgA) and immunoglobulin M (IgM) are usually assembled into dimers or pentamers with the contribution of joining (J)-chains, which bind to the secretory component (SC) of the polymeric Ig receptor (pIgR) and are transported to the mucosal surface. IgA and IgM play a pivotal role in various immune responses, especially in mucosal immunity. Due to their structural complexity, 3D structural study of these molecules at atomic scale has been slow. With the emergence of cryo-EM and X-ray crystallographic techniques and the growing interest in the structure-function relationships of IgA and IgM, atomic-scale structural information on IgA-Fc and IgM-Fc has been accumulating. Here, we examine the 3D structures of IgA and IgM, including the J-chain and SC. Disulfide bridging and N-glycosylation on these molecules are also summarized. With the increasing information of structure–function relationships, IgA- and IgM-based monoclonal antibodies will be an effective option in the therapeutic field. Full article