Search Results (21)

Artificial insemination (AI) is a key breeding technique in the swine industry; however, the lack of reliable biomarkers for semen quality limits its effectiveness. Seminal plasma (SP) contains extracellular vesicles (EVs) that present a promising, non-invasive biomarker for semen quality. This study explores the biochemical profiles of boar SP to assess semen quality through near-infrared spectroscopy (NIRS) and proteomics of SP-EVs. Fresh semen from mature Duroc boars was evaluated based on sperm motility, classifying samples as Passed (≥70%) or Failed (<70%). NIRS analysis identified distinct variations in water structures at specific wavelengths (C1, C5, C12 nm), achieving high accuracy (92.2%), sensitivity (94.2%), and specificity (90.3%) through PCA-LDA. Proteomic analysis of SP-EVs revealed 218 proteins in Passed and 238 in Failed samples. Nexin-1 and seminal plasma protein pB1 were upregulated in Passed samples, while LGALS3BP was downregulated. The functional analysis highlighted pathways associated with single fertilization, filament organization, and glutathione metabolism in Passed samples. Integrating NIRS with SP-EV proteomics provides a robust approach to non-invasive assessment of semen quality. These findings suggest that SP-EVs could serve as effective biosensors for rapid semen quality assessment, enabling better boar semen selection and enhancing AI practices in swine breeding. Full article

Background/Objectives: Cell–cell communication (CCC) is a critical process within the tumor microenvironment, governing regulatory interactions between cancer cells and other cellular subpopulations. Aiming to improve the accuracy and completeness of intercellular gene-regulatory network inference, we constructed a novel spatial-resolved gene-regulatory network framework (spGRN). Methods: Firstly, the spatial multi-omics data of colorectal cancer (CRC) patients were analyzed. We precisely located the tumor boundaries and then systematically constructed the spGRN framework to study the network regulation. Subsequently, the key signaling molecules obtained by the spGRN were identified and further validated by the spatial-proteomics dataset. Results: Through the constructed spatial gene regulatory network, we found that in the communication with malignant cells, the highly expressed ligands LIF and LGALS3BP and receptors IL6ST and ITGB1 in fibroblasts can promote tumor proliferation, and the highly expressed ligands S100A8/S100A9 in plasma cells play an important role in regulating inflammatory responses. Further, validation of the key signaling molecules by the spatial-proteomics dataset highlighted the role of these genes in mediating the regulation of boundary-related cells. Furthermore, we applied the spGRN to publicly available single-cell and spatial-transcriptomics datasets from three other cancer types. The results demonstrate that ITGB1 and its target genes FOS/JUN were commonly expressed in all four cancer types, indicating their potential as pan-cancer therapeutic targets. Conclusion: the spGRN was proven to be a useful tool to select signal molecules as potential biomarkers or valuable therapeutic targets. Full article

Space exploration has progressed from contemporary discoveries to current endeavors, such as space tourism and Mars missions. As human activity in space accelerates, understanding the physiological effects of microgravity on the human body is becoming increasingly critical. This study analyzes transcriptomic data from human cell lines exposed to microgravity, investigates its effects on gene expression, and identifies potential therapeutic interventions for health challenges posed by spaceflight. Our analysis identified five under-expressed genes (DNPH1, EXOSC5, L3MBTL2, LGALS3BP, SPRYD4) and six over-expressed genes (CSGALNACT2, CSNK2A2, HIPK1, MBNL2, PHF21A, RAP1A), all of which exhibited distinct expression patterns in response to microgravity. Enrichment analysis highlighted significant biological functions influenced by these conditions, while in silico drug repurposing identified potential modulators that could counteract these changes. This study introduces a novel approach to addressing health challenges during space missions by repurposing existing drugs and identifies specific genes and pathways as potential biomarkers for microgravity effects on human health. Our findings represent the first systematic effort to repurpose drugs for spaceflight, establishing a foundation for the development of targeted therapies for astronauts. Future research should aim to validate these findings in authentic space environments and explore broader biological impacts. Full article

Background/Objectives: SARS-CoV-2 is one of the viruses that caused worldwide health issues. This effect is mainly due to the wide range of disease prognoses it can cause. The aim of this study is to determine protein profiles that can be used as potential biomarkers for patients’ stratification, as well as potential targets for drug development. Methods: Eighty peripheral blood samples were collected from heathy as well as SARS-CoV-2 patients admitted at a major tertiary care center in Riyadh, Saudi Arabia. A label-free quantitative mass spectrometry-based proteomic analysis was conducted on the extracted sera. Protein–protein interactions and functional annotations of identified proteins were performed using the STRING. Results: In total, two-hundred-eighty-eight proteins were dysregulated among all four categories. Dysregulated proteins were mainly involved in the network map of SARS-CoV-2, immune responses, complement activation, and lipid transport. Compared to healthy subjects, the most common upregulated protein in all three categories were CRP, LGALS3BP, SAA2, as well as others involved in SARS-CoV-2 pathways such as ZAP70 and IGLL1. Notably, we found fifteen proteins that significantly discriminate between healthy/recovered subjects and moderate/under medication patients, among which are the SERPINA7, HSPD1 and TTC41P proteins. These proteins were also significantly downregulated in under medication versus moderate patients. Conclusions: Our results emphasize the possible association of specific proteins with the SARS-CoV-2 pathogenesis and their potential use as disease biomarkers and drug targets. Our study also gave insights about specific proteins that are likely increased upon infection but are likely restored post recovery. Full article

Microglia, the resident macrophages of the central nervous system, exhibit altered gene expression in response to various neurological conditions. This study investigates the relationship between West Nile Virus infection and microglial senescence, focusing on the role of LGALS3BP, a protein implicated in both antiviral responses and aging. Using spatial transcriptomics, RNA sequencing and flow cytometry, we characterized changes in microglial gene signatures in adult and aged mice following recovery from WNV encephalitis. Additionally, we analyzed Lgals3bp expression and generated Lgals3bp-deficient mice to assess the impact on neuroinflammation and microglial phenotypes. Our results show that WNV-activated microglia share transcriptional signatures with aged microglia, including upregulation of genes involved in interferon response and inflammation. Lgals3bp was broadly expressed in the CNS and robustly upregulated during WNV infection and aging. Lgals3bp-deficient mice exhibited reduced neuroinflammation, increased homeostatic microglial numbers, and altered T cell populations without differences in virologic control or survival. These data indicate that LGALS3BP has a role in regulating neuroinflammation and microglial activation and suggest that targeting LGALS3BP might provide a potential route for mitigating neuroinflammation-related cognitive decline in aging and post-viral infections. Full article

Brain cancer is a devastating and life-changing disease. Biomarkers are becoming increasingly important in addressing clinical issues, including in monitoring tumour progression and assessing survival and treatment response. The goal of this study was to identify prognostic biomarkers associated with glioma progression. Discovery proteomic analysis was performed on a small cohort of astrocytomas that were diagnosed as low-grade and recurred at a higher grade. Six proteins were chosen to be validated further in a larger cohort. Three proteins, CA9, CYFIP2, and LGALS3BP, were found to be associated with glioma progression and, in univariate analysis, could be used as prognostic markers. However, according to the results of multivariate analysis, these did not remain significant. These three proteins were then combined into a three-protein panel. This panel had a specificity and sensitivity of 0.7459 for distinguishing between long and short survival. In silico data confirmed the prognostic significance of this panel. Full article

Compared to Chinese indigenous sheep, Western sheep have rapid growth rate, larger physique, and higher meat yield. These excellent Western sheep were introduced into China for crossbreeding to expedite the enhancement of production performance and mutton quality in local breeds. Here, we investigated population genetic structure and genome-wide selection signatures among the Chinese indigenous sheep and the introduced sheep based on whole-genome resequencing data. The PCA, N-J tree and ADMIXTURE results showed significant genetic difference between Chinese indigenous sheep and introduced sheep. The nucleotide diversity (π) and linkage disequilibrium (LD) decay results indicated that the genomic diversity of introduced breeds were lower. Then, F_st & π ratio, XP-EHH, and de-correlated composite of multiple signals (DCMS) methods were used to detect the selection signals. The results showed that we identified important candidate genes related to growth rate and body size in the introduced breeds. Selected genes with stronger selection signatures are associated with growth rate (CRADD), embryonic development (BVES, LIN28B, and WNT11), body size (HMGA2, MSRB3, and PTCH1), muscle development and fat metabolism (MSTN, PDE3A, LGALS12, GGPS1, and SAR1B), wool color (ASIP), and hair development (KRT71, KRT74, and IRF2BP2). Thus, these genes have the potential to serve as candidate genes for enhancing the growth traits of Chinese indigenous sheep. We also identified tail-length trait-related candidate genes (HOXB13, LIN28A, PAX3, and VEGFA) in Chinese long-tailed breeds. Among these genes, HOXB13 is the main candidate gene for sheep tail length phenotype. LIN28A, PAX3, and VEGFA are related to embryonic development and angiogenesis, so these genes may be candidate genes for sheep tail type traits. This study will serve as a foundation for further genetic improvement of Chinese indigenous sheep and as a reference for studies related to growth and development of sheep. Full article

Tunchang pig is one population of Hainan pig in the Hainan Province of China, with the characteristics of delicious meat, strong adaptability, and high resistance to diseases. To explore the genetic diversity and population structure of Tunchang pigs and uncover their germplasm characteristics, 10 unrelated Tunchang pigs were re-sequenced using the Illumina NovaSeq 150 bp paired-end platform with an average depth of 10×. Sequencing data from 36 individuals of 7 other pig breeds (including 4 local Chinese pig breeds (5 Jinhua, 5 Meishan, 5 Rongchang, and 6 Wuzhishan), and 3 commonly used commercial pig breeds (5 Duorc, 5 Landrace, and 5 Large White)) were downloaded from the NCBI public database. After analysis of genetic diversity and population structure, it has been found that compared to commercial pigs, Tunchang pigs have higher genetic diversity and are genetically close to native Chinese breeds. Three methods, F_ST, θπ, and XP-EHH, were used to detect selection signals for three breeds of pigs: Tunchang, Duroc, and Landrace. A total of 2117 significantly selected regions and 201 candidate genes were screened. Gene enrichment analysis showed that candidate genes were mainly associated with good adaptability, disease resistance, and lipid metabolism traits. Finally, further screening was conducted to identify potential candidate genes related to phenotypic traits, including meat quality (SELENOV, CBR4, TNNT1, TNNT3, VPS13A, PLD3, SRFBP1, and SSPN), immune regulation (CD48, FBL, PTPRH, GNA14, LOX, SLAMF6, CALCOCO1, IRGC, and ZNF667), growth and development (SYT5, PRX, PPP1R12C, and SMG9), reproduction (LGALS13 and EPG5), vision (SLC9A8 and KCNV2), energy metabolism (ATP5G2), cell migration (EPS8L1), and olfaction (GRK3). In summary, our research results provide a genomic overview of the genetic variation, genetic diversity, and population structure of the Tunchang pig population, which will be valuable for breeding and conservation of Tunchang pigs in the future. Full article

Loneliness and social isolation are detrimental to mental health and may lead to cognitive impairment and neurodegeneration. Although several molecular signatures of loneliness have been identified, the molecular mechanisms by which loneliness impacts the brain remain elusive. Here, we performed a bioinformatics approach to untangle the molecular underpinnings associated with loneliness. Co-expression network analysis identified molecular ‘switches’ responsible for dramatic transcriptional changes in the nucleus accumbens of individuals with known loneliness. Loneliness-related switch genes were enriched in cell cycle, cancer, TGF-β, FOXO, and PI3K-AKT signaling pathways. Analysis stratified by sex identified switch genes in males with chronic loneliness. Male-specific switch genes were enriched in infection, innate immunity, and cancer-related pathways. Correlation analysis revealed that loneliness-related switch genes significantly overlapped with 82% and 68% of human studies on Alzheimer’s (AD) and Parkinson’s diseases (PD), respectively, in gene expression databases. Loneliness-related switch genes, BCAM, NECTIN2, NPAS3, RBM38, PELI1, DPP10, and ASGR2, have been identified as genetic risk factors for AD. Likewise, switch genes HLA-DRB5, ALDOA, and GPNMB are known genetic loci in PD. Similarly, loneliness-related switch genes overlapped in 70% and 64% of human studies on major depressive disorder and schizophrenia, respectively. Nine switch genes, HLA-DRB5, ARHGAP15, COL4A1, RBM38, DMD, LGALS3BP, WSCD2, CYTH4, and CNTRL, overlapped with known genetic variants in depression. Seven switch genes, NPAS3, ARHGAP15, LGALS3BP, DPP10, SMYD3, CPXCR1, and HLA-DRB5 were associated with known risk factors for schizophrenia. Collectively, we identified molecular determinants of loneliness and dysregulated pathways in the brain of non-demented adults. The association of switch genes with known risk factors for neuropsychiatric and neurodegenerative diseases provides a molecular explanation for the observed prevalence of these diseases among lonely individuals. Full article

Background: Studies showed that folate and related single nucleotide polymorphisms (SNPs) could predict prostate cancer (PCa) risk. However, little is known about the interactions of folate-related SNPs associated with PCa aggressiveness. The study’s objective is to evaluate SNP–SNP interactions among the DHFR 19-bp polymorphism and 10 SNPs in folate metabolism and the one-carbon metabolism pathway associated with PCa aggressiveness. Methods: We evaluated 1294 PCa patients, including 690 European Americans (EAs) and 604 African Americans (AAs). Both individual SNP effects and pairwise SNP–SNP interactions were analyzed. Results: None of the 11 individual polymorphisms were significant for EAs and AAs. Three SNP–SNP interaction pairs can predict PCa aggressiveness with a medium to large effect size. For the EA PCa patients, the interaction between rs1801133 (MTHFR) and rs2236225 (MTHFD1), and rs1801131 (MTHFR) and rs7587117 (SLC4A5) were significantly associated with aggressive PCa. For the AA PCa patients, the interaction of DHFR-19bp polymorphism and rs4652 (LGALS3) was significantly associated with aggressive PCa. Conclusions: These SNP–SNP interactions in the folate metabolism-related genes have a larger impact than SNP individual effects on tumor aggressiveness for EA and AA PCa patients. These findings can provide valuable information for potential biological mechanisms of PCa aggressiveness. Full article

Key proteins transferred by epididymal extracellular vesicles (EVs) to the transiting sperm cells contribute to their centrosomal maturation and developmental potential. Although not reported in sperm cells yet, galectin-3-binding protein (LGALS3BP) is known to regulate centrosomal functions in somatic cells. Using the domestic cat model, the objectives of this study were to (1) detect the presence and characterize the transfer of LGALS3BP via EVs between the epididymis and the maturing sperm cells and (2) demonstrate the impact of LGALS3BP transfer on sperm fertilizing ability and developmental potential. Testicular tissues, epididymides, EVs, and spermatozoa were isolated from adult individuals. For the first time, this protein was detected in EVs secreted by the epididymal epithelium. The percentage of spermatozoa with LGALS3BP in the centrosome region increased as cells progressively incorporated EVs during the epididymal transit. When LGALS3BP was inhibited during in vitro fertilization with mature sperm cells, less fertilized oocytes and slower first cell cycles were observed. When the protein was inhibited in epididymal EVs prior to incubation with sperm cells, poor fertilization success further demonstrated the role of EVs in the transfer of LGALS3BP to the spermatozoa. The key roles of this protein could lead to new approaches to enhance or control fertility in clinical settings. Full article

To identify the novel genes involved in chemoresistance in head and neck squamous cell carcinoma (HNSCC), we explored the expression profiles of the following cisplatin (CDDP) resistant (R) versus parental (sensitive) cell lines by RNA-sequencing (RNA-seq): JHU029, HTB-43 and CCL-138. Using the parental condition as a control, 30 upregulated and 85 downregulated genes were identified for JHU029-R cells; 263 upregulated and 392 downregulated genes for HTB-43-R cells, and 154 upregulated and 68 downregulated genes for CCL-138-R cells. Moreover, we crossed-checked the RNA-seq results with the proteomic profiles of HTB-43-R (versus HTB-43) and CCL-138-R (versus CCL-138) cell lines. For the HTB-43-R cells, 21 upregulated and 72 downregulated targets overlapped between the proteomic and transcriptomic data; whereas in CCL-138-R cells, four upregulated and three downregulated targets matched. Following an extensive literature search, six genes from the RNA-seq (CLDN1, MAGEB2, CD24, CEACAM6, IL1B and ISG15) and six genes from the RNA-seq and proteomics crossover (AKR1C3, TNFAIP2, RAB7A, LGALS3BP, PSCA and SSRP1) were selected to be studied by qRT-PCR in 11 HNSCC patients: six resistant and five sensitive to conventional therapy. Interestingly, the high MAGEB2 expression was associated with resistant tumours and is revealed as a novel target to sensitise resistant cells to therapy in HNSCC patients. Full article

Background: Malignant melanoma is the most serious type of skin cancer with the highest mortality rate. Extracellular vesicles (EVs) have potential as new tumor markers that could be used as diagnostic and prognostic markers for early detection of melanoma. Methods: EVs were purified from the blood serum of melanoma patients using two methods—ultracentrifugation and PEG precipitation—and analyzed by mass spectrometry and immunoblot. Results: We identified a total of 585 unique proteins; 334 proteins were detected in PEG-precipitated samples and 515 in UC-purified EVs. EVs purified from patients varied in their size and concentration in different individuals. EVs obtained from stage II and III patients were, on average, smaller and more abundant than others. Detailed analysis of three potential biomarkers—SERPINA3, LGALS3BP, and gelsolin—revealed that the expression of SERPINA3 and LGALS3BP was higher in melanoma patients than healthy controls, while gelsolin exhibited higher expression in healthy controls. Conclusion: We suggest that all three proteins might have potential to be used as biomarkers, but a number of issues, such as purification of EVs, standardization, and validation of methods suitable for everyday clinical settings, still need to be addressed. Full article

Severe obesity is a disease associated with multiple adverse effects on health. Metabolic bariatric surgery (MBS) can have significant effects on multiple body systems and was shown to improve inflammatory markers in previous short-term follow-up studies. We evaluated associations between changes in inflammatory markers (CRP, IL6 and TNFα) and circulating proteins after MBS. Methods: Sequential window acquisition of all theoretical mass spectra (SWATH-MS) proteomics was performed on plasma samples taken at baseline (pre-surgery) and 6 and 12 months after MBS, and concurrent analyses of inflammatory/metabolic parameters were carried out. The change in absolute abundances of those proteins, showing significant change at both 6 and 12 months, was tested for correlation with the absolute and percentage (%) change in inflammatory markers. Results: We found the following results: at 6 months, there was a correlation between %change in IL-6 and fold change in HSPA4 (rho = −0.659; p = 0.038) and in SERPINF1 (rho = 0.714, p = 0.020); at 12 months, there was a positive correlation between %change in IL-6 and fold change in the following proteins—LGALS3BP (rho = 0.700, p = 0.036), HSP90B1 (rho = 0.667; p = 0.05) and ACE (rho = 0.667, p = 0.05). We found significant inverse correlations at 12 months between %change in TNFα and the following proteins: EPHX2 and ACE (for both rho = −0.783, p = 0.013). We also found significant inverse correlations between %change in CRP at 12 months and SHBG (rho = −0.759, p = 0.029), L1CAM (rho = −0.904, p = 0.002) and AMBP (rho = −0.684, p = 0.042). Conclusion: Using SWATH-MS, we identified several proteins that are involved in the inflammatory response whose levels change in patients who achieve remission of T2DM after bariatric surgery in tandem with changes in IL6, TNFα and/or CRP. Future studies are needed to clarify the underlying mechanisms in how MBS decreases low-grade inflammation. Full article

In recent years, brown adipose tissue (BAT), which has a high heat-producing capacity, has been confirmed to exist even in adults, and it has become a focal point for the prevention and the improvement of obesity and lifestyle-related diseases. However, the influences of obesity and physical activity (PA) on the fluid factors secreted from BAT (brown adipokines) are not well understood. In this study, therefore, we focused on brown adipokines and investigated the effects of obesity and PA. The abnormal expressions of gene fluid factors such as galectin-3 (Lgals3) and Lgals3 binding protein (Lgals3bp), whose proteins are secreted from HB2 brown adipocytes, were observed in the interscapular BAT of obese mice fed a high-fat diet for 4 months. PA attenuated the abnormalities in the expressions of these genes. Furthermore, although the gene expressions of factors related to brown adipocyte differentiation such as peroxisome proliferator-activated receptor gamma coactivator 1-α were also down-regulated in the BAT of the obese mice, PA suppressed the down-regulation of these factors. On the other hand, lipogenesis was increased more in HB2 cells overexpressing Lgals3 compared with that in control cells, and the overexpression of Lgals3bp decreased the mitochondrial mass. These results indicate that PA attenuates the obesity-induced dysregulated expression of brown adipokines and suggests that Lgals3 and Lgals3bp are involved in brown adipocyte differentiation. Full article