Differential Protein Expression Research Articles

Exploring the mechanism of Jianpi Lishi Jiedu Granules against postoperative recurrence of colorectal adenoma based on IL-6/JAK/STAT3 signaling pathway

Globally, colorectal cancer (CRC) is the primary cause of cancer-related fatalities. Our previous study demonstrated the efficacy of Jianpi Lishi Jiedu Granules (JLJG) in preventing postoperative recurrence of colorectal adenoma (CRA). Building on this foundation, the current study aims to elucidate whether the mechanism by which JLJG prevents postoperative recurrence of CRA involves the classical JAK/STAT inflammatory signaling pathway and to assess its specific impact on this pathway. Utilizing proteomics, we discerned 143 differentially expressed proteins (DEPs) regulated by JLJG, whose functional roles are intimately linked to the JAK/STAT signaling pathway. Among these, we identified key proteins such as IL-6, JAK1, JAK2, STAT3, CCND1, MYC, Bcl-XL, and SOCS3 that are regulated by JLJG and play pivotal roles in the JAK/STAT signaling cascade. Our findings indicate that the sustained activation of the IL-6/JAK/STAT3 signaling pathway is significantly associated with CRA recurrence. JLJG was found to effectively modulate the expression levels of these proteins, as well as the expression of downstream genes including BCL2, MCL1, P21, and JAK1, STAT3, thereby inhibiting the IL-6/JAK/STAT3 signaling pathway. Consequently, this study demonstrates that JLJG prevents the postoperative recurrence of CRA by inhibiting the IL-6/JAK/STAT3 signaling pathway and its negative feedback loops.

The ultrastructural and proteomic analysis of mitochondria-associated endoplasmic reticulum membrane in the midbrain of a Parkinson's disease mouse model.

Recent studies indicated that the dysregulation of mitochondria-associated endoplasmic reticulum membrane (MAM) could be a significant hub in the pathogenesis of Parkinson's disease (PD). However, little has been known about how MAM altered in PD. This study was aimed to observe morphological changes and analyze proteomic profiles of MAM in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models. In MPTP-treated mice, transmission electron microscopy was applied for MAM ultrastructural visualization. Nano ultra-high performance liquid chromatography-tandem mass spectrum and bioinformatic analysis were adopted to obtain underlying molecular data of MAM fractions. The loosened, shortened and reduced MAM tethering was found in substantia nigral neurons from MPTP-treated mice. In midbrain MAM proteomics, 158 differentially expressed proteins (DEPs) were identified between two groups. Specific DEPs were validated by western blot and exhibited significantly statistical changes, aligning with proteomic results. Bioinformatic analysis indicated that membrane, cytoplasm and cell projection were three major localizations for DEPs. Biological processes including metabolism, lipid transport, and immunological and apoptotic signaling pathways were greatly affected. For consensus MAM proteins, the enriched pathway analysis revealed the potential relationship between neurodegenerative diseases and MAM. Several biological processes such as peroxisome function and clathrin-mediated endocytosis, were clustered, which provided additional insights into the fundamental molecular pathways associated with MAM. In our study, we demonstrated disrupted ER-mitochondria contacts in an MPTP-induced PD mouse model. The underlying signatures of MAM were revealed by proteomics and bioinformatic analysis, providing valuable insights into its potential role in PD pathogenesis.

Proteomic analysis illustrates the potential involvement of dysregulated ribosome-related pathways and disrupted metabolism during retinoic acid-induced cleft palate development

Recent studies have unveiled disrupted metabolism in the progression of cleft palate (CP), a congenital anomaly characterized by defective fusion of facial structures. Nonetheless, the precise composition of this disrupted metabolism remains elusive, prompting us to identify these components and elucidate primary metabolic irregularities contributing to CP pathogenesis. We established a murine CP model by retinoic acid (RA) treatment and analyzed control and RA-treated embryonic palatal tissues by LC-MS-based proteomic approach. We identified 220 significantly upregulated and 224 significantly downregulated proteins. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that these differentially expressed proteins (DEPs) were involved in translation, ribosome assembly, mitochondrial function, mRNA binding, as well as key metabolic pathways like oxidative phosphorylation (OXPHOS), glycolysis/gluconeogenesis, and amino acid biosynthesis. These findings suggest that dysregulated ribosome-related pathways and disrupted metabolism play a critical role in CP development. Protein-protein interaction analysis using the STRING database revealed a tightly connected network of DEPs. Furthermore, we identified the top 10 hub proteins in CP using the Cytohubba plugin in Cytoscape. These hub proteins, including RPL8, RPS11, ALB, PA2G4, RPL23, RPS6, CCT7, EGFR, HSPD1, and RPS28, are potentially key regulators of CP pathogenesis. In conclusion, our comprehensive proteomic analysis provides insights into the molecular alterations associated with RA-induced CP in Kun Ming mice. These findings suggest potential therapeutic targets and pathways to understand and prevent congenital craniofacial anomalies.

Proteomic profiling of the local and systemic immune response to pediatric respiratory viral infections.

Viral lower respiratory tract infection (vLRTI) is a leading cause of hospitalization and death in children worldwide. Despite this, no studies have employed proteomics to characterize host immune responses to severe pediatric vLRTI in both the lower airway and systemic circulation. To address this gap, gain insights into vLRTI pathophysiology, and test a novel diagnostic approach, we assayed 1,305 proteins in tracheal aspirate (TA) and plasma from 62 critically ill children using SomaScan. We performed differential expression (DE) and pathway analyses comparing vLRTI (n = 40) to controls with non-infectious acute respiratory failure (n = 22), developed a diagnostic classifier using LASSO regression, and analyzed matched TA and plasma samples. We further investigated the impact of viral load and bacterial coinfection on the proteome. The TA signature of vLRTI was characterized by 200 DE proteins (Padj <0.05) with upregulation of interferons and T cell responses and downregulation of inflammation-modulating proteins including FABP and MIP-5. A nine-protein TA classifier achieved an area under the receiver operator curve (AUC) of 0.96 (95% CI: 0.90-1.00) for identifying vLRTI. In plasma, the host response to vLRTI was more muted with 56 DE proteins. Correlation between TA and plasma was limited, although ISG15 was elevated in both compartments. In bacterial coinfection, we observed increases in the TNF-stimulated protein TSG-6, as well as CRP, and interferon-related proteins. Viral load correlated positively with interferon signaling and negatively with neutrophil-activation pathways. Taken together, our study provides fresh insights into the lower airway and systemic proteome of severe pediatric vLRTI and identifies novel protein biomarkers with diagnostic potential.IMPORTANCEWe describe the first proteomic profiling of the lower airway and blood in critically ill children with severe viral lower respiratory tract infection (vLRTI). From tracheal aspirate (TA), we defined a proteomic signature of vLRTI characterized by increased expression of interferon signaling proteins and decreased expression of proteins involved in immune modulation including FABP and MIP-5. Using machine learning, we developed a parsimonious diagnostic classifier that distinguished vLRTI from non-infectious respiratory failure with high accuracy. Comparative analysis of paired TA and plasma specimens demonstrated limited concordance, although the interferon-stimulated protein ISG15 was significantly upregulated with vLRTI in both compartments. We further identified TSG-6 and CRP as airway biomarkers of bacterial-viral coinfection, and viral load analyses demonstrated a positive correlation with interferon-related protein expression and a negative correlation with the expression of neutrophil activation proteins. Taken together, our study provides new insights into the lower airway and systemic proteome of severe pediatric vLRTI.

Comprehensive transcriptomic, proteomic, and intestinal microbiota analyses of largemouth bass (Micropterus salmoides) intestines reveal new insights into immune responses to Aeromonas hydrophila infection

This study investigates the immune responses of largemouth bass (Micropterus salmoides) to infection by Aeromonas hydrophila, a pathogen responsible for significant economic losses in freshwater aquaculture due to bacterial enteritis. We employed transcriptomic sequencing, label-free LC-MS/MS quantitative proteomics, and 16S RNA sequencing to evaluate the transcriptomic, proteomic, and intestinal microbiota changes in infected fish compared to healthycontrols. Each fish (approximately 60 g) in the infection group was injected with 0.5 ml of an A. hydrophila suspension (1.0 × 108 CFU/mL), while the control group received 0.5 ml of phosphate buffer. Samples were collected 72 h post-injection, with three biological replicates made from an equal mix of tissue samples from six fish each. A total of 1666 differentially expressed genes (DEGs) and 2477 differentially expressed proteins (DEPs) were identified. Integrated analysis revealed that the up-regulated DEGs/DEPs in the intestines of infected largemouth bass were primarily associated with immune-related pathways including "antigen processing and presentation", "MAPK signaling pathway", "ECM-receptor interaction", and "leukocyte transendothelial migration". Notable upregulated immune-related proteins included complement or antigen-presenting proteins like complement C1, complement C3, complement C6, ɑ-2-macroglobulin, laminin, serotransferrin, leukocyte cell-derived chemotaxin-2, immunoglobulin C1-set domain-containing protein, and the MHC class I alpha antigen. 16S RNA sequencing indicated a significant increase in Proteobacteria and a decrease in Fusobacteria in the intestines of infected fish compared to controls. Collectively, these findings demonstrate that A. hydrophila infection significantly alters gene and protein expression as well as intestinal microbiota in largemouth bass, providing insights into their immune defense mechanisms against infection.

The Dual Resistance Mechanism of CYP325G4 and CYP6AA9 in Culex pipiens pallens Legs According to Transcriptome and Proteome Analysis.

Mosquitoes within the Culex pipiens complex play a crucial role in human disease transmission. Insecticides, especially pyrethroids, are used to control these vectors. Mosquito legs are the main entry point and barrier for insecticides to gain their neuronal targets. However, the resistance mechanism in mosquito legs is unclear. Herein, we employed transcriptomic analyses and isobaric tags for relative and absolute quantitation techniques to investigate the resistance mechanism, focusing on Cx. pipiens legs. We discovered 2346 differentially expressed genes (DEGs) between deltamethrin-resistant (DR) and deltamethrin-sensitive (DS) mosquito legs, including 41 cytochrome P450 genes. In the same comparison, we identified 228 differentially expressed proteins (DEPs), including six cytochrome P450 proteins. Combined transcriptome and proteome analysis revealed only two upregulated P450 genes, CYP325G4 and CYP6AA9. The main clusters of DEGs and DEPs were associated with metabolic processes, such as cytochrome P450-mediated metabolism of drugs and xenobiotics. Transcription analysis revealed high CYP325G4 and CYP6AA9 expression in the DR strain at 72 h posteclosion compared with that in the DS strain, particularly in the legs. Mosquitoes knocked down for CYP325G4 were more sensitive to deltamethrin than the controls. CYP325G4 knockdown reduced the expression of several chlorinated hydrocarbon (CHC)-related genes, which altered the cuticle thickness and structure. Conversely, CYP6AA9 knockdown increased CHC gene expression without altering cuticle thickness and structure. P450 activity analysis demonstrated that CYP325G4 and CYP6AA9 contributed to metabolic resistance in the midgut and legs. This study identified CYP325G4 as a novel mosquito deltamethrin resistance factor, being involved in both metabolic and cuticular resistance mechanisms. The previously identified CYP6AA9 was investigated for its involvement in metabolic resistance and potential cuticular resistance in mosquito legs. These findings enhance our comprehension of resistance mechanisms, identifying P450s as promising targets for the future management of mosquito vector resistance, and laying a theoretical groundwork for mosquito resistance management.

Multi-targeted olink proteomics analyses of cerebrospinal fluid from patients with aneurysmal subarachnoid hemorrhage

BackgroundThe complexity of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) may require the simultaneous analysis of variant types of protein biomarkers to describe it more accurately. In this study, we analyzed for the first time the alterations of cerebrospinal fluid (CSF) proteins in patients with aSAH by multi-targeted Olink proteomics, aiming to reveal the pathophysiology of DCI and provide insights into the diagnosis and treatment of aSAH.MethodsSix aSAH patients and six control patients were selected, and CSF samples were analyzed by Olink Proteomics (including 96-neurology panel and 96-inflammation panel) based on Proximity Extension Assay (PEA). Differentially expressed proteins (DEPs) were acquired and bioinformatics analysis was performed.ResultsPCA analysis revealed better intra- and inter-group reproducibility of CSF samples in the control and aSAH groups. 23 neurology-related and 31 inflammation-relevant differential proteins were identified. In the neurology panel, compared to controls, the up-regulated proteins in the CSF of SAH patients predominantly included macrophage scavenger receptor 1 (MSR1), siglec-1, siglec-9, cathepsin C (CTSC), cathepsin S (CTSS), etc. Meanwhile, in the inflammation group, the incremental proteins mainly contained interleukin-6 (IL-6), MCP-1, CXCL10, CXCL-9, TRAIL, etc. Cluster analysis exhibited significant differences in differential proteins between the two groups. GO function enrichment analysis hinted that the differential proteins pertinent to neurology in the CSF of SAH patients were mainly involved in the regulation of defense response, vesicle-mediated transport and regulation of immune response; while the differential proteins related to inflammation were largely connected with the cellular response to chemokine, response to chemokine and chemokine-mediated signaling pathway. Additionally, in the neurology panel, KEGG enrichment analysis indicated that the differential proteins were significantly enriched in the phagosome, apoptosis and microRNAs in cancer pathway. And in the inflammation panel, the differential proteins were mainly enriched in the chemokine signaling pathway, viral protein interaction with cytokine and cytokine receptor and toll-like receptor signaling pathway.ConclusionsThese identified differential proteins reveal unique pathophysiological characteristics secondary to aSAH. Further characterization of these proteins and aberrant pathways in future research could enable their application as potential therapeutic targets and biomarkers for DCI after aSAH.

Chronic Hypobaric Hypoxia Stimulates Differential Expression of Cognitive Proteins in Hippocampal Tissue.

Objective: We aimed to determine changes in cognitive function resulting from chronic hypobaric hypoxia through proteomic analysis of hippocampal tissue. We screened cognition-related proteins to provide ideas and directions that could help prevent and treat hypoxia-associated cognitive impairment. Methods: We analyzed hippocampal tissues from mice exposed to high altitudes and control mice using 4 D label-free quantitative proteomics. The data were analyzed by protein quantitative analysis, functional annotation, differential protein screening, clustering analyses, and functional classification and enrichment. Differential protein expression was investigated using targeted quantitative omics based on parallel response monitoring. Results: We identified and quantified 20 target proteins in 12 samples, of which 18 were significant validated proteins that were or might be related to cognitive functions. Signaling pathways that were significantly enriched in differentially expressed proteins were pyrimidine metabolism, 5'-Adenosine Triphosphate-activated protein kinase signaling, phospholipase D signaling, purine metabolism, inflammatory mediator regulation of transient receptor potential channels, hedgehog signaling pathways, dilated cardiomyopathy, platelet activation, insulin resistance, mRNA surveillance pathways, drug metabolism-other enzymes, and drug metabolism-cytochrome P450. Conclusion: Chronic hypoxia alters protein expression in murine hippocampal tissues. Eighteen differentially expressed cognition-related proteins might be related to cognitive impairment in mice exposed to chronic high-altitude hypoxia.

ITRAQ-Based Proteomic Analysis of Spontaneous Achilles Tendon Rupture.

Spontaneous Achilles tendon rupture (SATR) predominantly affects middle-aged and elderly individuals with chronic injuries. However, the exact cause and mechanism of SATR remain elusive, and potential therapeutic intervention or prevention is still insufficient. The present study aimed to uncover the key pathological molecules by using iTRAQ proteomics. The results identified 2432 candidate proteins in SATR patients using iTRAQ proteomic analysis. A total of 307 differentially expressed proteins (DEPs) were identified and linked to 211 KEGG signaling pathways including Coronavirus disease (COVID-19), focal adhesion, and ribosomes. GO enrichment analysis highlighted significant enrichment in processes such as biological adhesion, ossification, lipid (APOA4) processes, and extracellular matrix (ECM) organization (collagen). PPI network analysis identified hub genes such as serum albumin (ALB), fibronectin (FN1), and actin cytoplasmic 1. The WB analysis confirmed that FN1 and the receptor for activated C kinase (RACK1) were downregulated in the SATR tendon. Immunohistochemical staining revealed that collagen I and III were suppressed, while collagen II and APOA4 expression were higher in the SATR pathological tissue (P < 0.05). However, the primary cultured tenocytes (PCTs) from SATR patients showed enhanced proliferation and, consistent with tissue staining, reduced collagen I and III and increased collagen II. Our findings reveal vital targets and pathways in SATR's etiological progression, offering a new perspective on the diagnosis, treatment, and prognosis of this complex disorder.

Directional and Strain-Specific Interaction Between Lactobacillus plantarum and Staphylococcus aureus

The interaction between Lactobacillus plantarum and Staphylococcus aureus strains FRI-1169 and MN8, two original isolated strains from menstrual toxic shock syndrome (mTSS) cases, is a key focus for developing non-antibiotic strategies to control S. aureus-related infections. While the antagonistic effects of Lactobacilli species on S. aureus through mechanisms like organic acid and bacteriocin production are known, the molecular dynamics of these interactions remain underexplored. This study employs a proteomic approach to analyze the interactions between L. plantarum WCFS1 and S. aureus strains, FRI-1169 and MN8, during co-culture. We profiled differentially expressed proteins (DEPs) found in the spent media and cytosols of both bacteria, revealing distinct directional and strain-specific responses. The findings demonstrate that L. plantarum exerts a more pronounced effect on S. aureus, with more DEPs and upregulated proteins, while S. aureus showed fewer DEPs and more downregulated proteins. These strain-specific interactions highlight the complex metabolic and regulatory adjustments between these bacterial species. This research provides valuable insights into the molecular mechanisms of Lactobacillus-S. aureus antagonism and underscores the potential of proteomic analysis as a powerful tool for studying bacterial dynamics in co-culture systems.

Molecular insights into oocyte development and sperm storage in black rockfish (Sebastes schlegelii): Proteomic changes across reproductive stages

Sperm storage in females is widespread among vertebrates and insects, and the expression of proteins in the female reproductive tract is influenced by the presence of sperm, allowing for adaptation to this phenomenon. Through histological observation, we confirmed that sperm were stored in the isthmic fossa outside the oocyte during the post-mating (POM) stage, and closer to the epithelial cells during the pre-fertilization (PRF) stage. In addition, we observed asynchronous ovarian development in black rockfish, where oocytes at various stages could be identified during the PRF phase. This study investigated the ovarian protein expression changes in black rockfish (Sebastes schlegelii) during key reproductive stages: pre-mating (PRM), POM, unmated control (POM-CT), and PRF. A total of 5012 proteins were identified, with notable fluctuations in protein expression observed at the PRF stage. Specifically, 140 proteins were upregulated and 615 downregulated when compared to the PRM stage, while 101 proteins were upregulated and 531 downregulated in comparison to the POM stage. The functional enrichment analysis of differentially expressed proteins (DEPs) revealed distinct pathways: POM vs. PRM showed involvement in vesicle sorting and hormone signaling; PRF vs. POM indicated pathways related to chromatin remodeling and gene expression regulation; and POM vs. POM-CT highlighted pathways associated with immune response. These findings suggested that these signaling pathways may play a crucial role in oocyte development and sperm storage. The majority of DEPs were localized in the nucleus, with key interactions involving proteins such as GSK3B and MED1. These findings enhance our understanding of the molecular mechanisms underlying oocyte maturation and sperm storage, providing insights relevant to reproductive biology and aquaculture practices.

Label-free quantitative proteomic analysis reveals the characteristics of ovarian development from stage II to III in Chinese sturgeon (Acipenser sinensis)

Chinese sturgeon (Acipenser sinensis) is an endangered anadromous and rare fish. The ovary development from stage II to III is being challenged by captive conditions, which seriously hinders the artificial reproduction of Chinese sturgeon. A comparative proteomic analysis on the ovaries at stage II and stage III of Chinese sturgeon was conducted in this study using the label-free quantitative method to uncover the intricate physiological processes. The findings revealed 200 up-regulated differentially expressed proteins (DEPs) and 150 down-regulated DEPs in the ovary at stage III compared with stage II, and 11 DEPs (including UCHL1, VTG, CTSD, and ZP, etc.) involved in the vitellogenesis and oocyte growth. Moreover, the up-regulated DEPs exhibited significant enrichment in the pathways linked to protein synthesis (ribosome, protein processing in the endoplasmic), metabolism and energy production (valine, leucine and isoleucine degradation, TCA cycle, oxidative phosphorylation, and fatty acid degradation), suggesting more active protein processing and energy metabolism at stage III. Meanwhile, APOB was down-regulated while VTG was up-regulated in stage III ovary, indicating the uptake of yolk protein and lipid through VTG at this stage. The parallel reaction monitoring (PRM) quantification of 16 DEPs solidly validated the outcomes of label-free analysis. This study provided powerful information for understanding the physiological processes of ovarian development in Chinese sturgeon, and potential biomarkers in predicting the vitellogenic stage.

Data-independent acquisition-based blood proteomics unveils predictive biomarkers for neonatal necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a life-threatening condition affecting preterm infants, sometimes necessitating surgical treatment. This study aimed to analyze differentially expressed proteins (DEPs) and access their biological and clinical significance in the plasma of neonates with NEC. Peripheral blood samples were collected from NEC infants at various time points, and plasma was separated. Data-independent acquisition (DIA) technology was utilized to identify DEPs among NEC patients at different stages. Bioinformatic analyses, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, and protein-to-protein interaction analyses were performed on the DEPs. External datasets, along with receiver operating characteristic curves and gene set enrichment analysis, were used to clinically and biologically validate the findings. DEPs between the NEC and pre-NEC groups indicated reduced protein, heme, nitrogen, and purine nucleotide biosynthesis during NEC formation. In addition, enriched DEPs among the NEC groups at different time points suggested reconstructed extracellular matrix, aberrant B-lymphocyte immune responses, and decreased glycosaminoglycan levelsduring NEC progression. These findings were both clinically and biologically validated using external datasets. Our study highlights the clinical and biological relevance of proteomics in NEC patients. This study demonstrates key pathways involved in NEC pathogenesis and establishes DIA mass spectrometry as a powerful and noninvasive tool for evaluating and predicting NEC formation and progression.

Screening and verification of differentially expressed serum proteins in children with severe adenovirus pneumonia.

Human adenoviruses are prevalent pathogens that cause severe acute respiratory infections. The clinical presentation of the adenoviral pneumonia is varied; in severe cases, they may cause systemic multi-system damages. Currently, early clinical differential diagnosis is difficult under the existing testing methods, the study identified potential biomarkers by screening and validating differentially expressed proteins (DEPs), and aimed at distinguishing between severe and non-severe adenovirus pneumonia in children aged <14 years. DEPs were identified using data-independent acquisition (DIA) quantitative proteomics technology, and potential biomarkers were further validated using an enzyme-linked immunosorbent assay (ELISA). Twenty-seven identical DEPs were found in patients with severe adenovirus pneumonia. Among these, 10 were downregulated, and 17 were upregulated. In the protein-protein interaction network, five proteins were located at the center of the functional network. Among these, E-selectin showed significantly higher serum expression levels in the severe adenoviral pneumonia group than in adenoviral pneumonia and control groups (p < 0.001). ELISA results were consistent with the proteomic analyses. The receiver operating characteristic (ROC) curve for E-selectin revealed a sensitivity of 79.31% and a specificity of 96.55%, with an area under the curve (AUC) of 0.92. E-selectin has potential as a novel biomarker for severe adenoviral pneumonia, and offers insights for improved diagnosis and clinical management.

Therapeutic potential of Simvastatin in ALS: Enhanced axonal integrity and motor neuron survival through Apoa4 and Alb modulation.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective death of motor neurons in the spinal cord, brainstem, and motor cortex. This study investigates the effects of simvastatin on the G93A-copper/zinc superoxide dismutase (G93ASOD1) transgenic mouse model of ALS. The experiment included three groups: C57BL/6 wild-type (WT) mice, C57BL/6J SOD1G93A mice treated with PBS (SOD1G93A + PBS), and C57BL/6J SOD1G93A mice treated with simvastatin (SOD1G93A + simvastatin). The primary endpoints were survival rates, body weight changes, performance in pole climbing and suspension tests, and neurological deficit scores. Pathological changes were assessed using H&E staining, transmission electron microscopy, Nissl staining, and Masson staining. Proteomic and metabolomic analyses were performed to identify differentially expressed proteins (DEPs) and metabolites. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to measure gene expression. Although there were no significant differences in survival rates, body weight, pole climbing, and suspension test performance, or neurological deficit scores between the SOD1G93A + simvastatin and SOD1G93A + PBS groups, simvastatin treatment improved axonal organization within the spinal cord, increased the number of neurons, and reduced cytoplasmic swelling and gastrocnemius fibrosis. A total of 47 DEPs and 13 differential metabolites were identified between the SOD1G93A + PBS and SOD1G93A + simvastatin groups. Notably, the expression levels of Apoa4 and Alb were elevated in the SOD1G93A + simvastatin group compared to the SOD1G93A + PBS group. Our results suggest that simvastatin may have potential therapeutic effects in ALS, likely involving the modulation of Apoa4 and Alb expression.

A study on the plasma proteomics of different types of depressive disorders based on label-free data-independent acquisition proteomic technology

BackgroundDue to the high incidence and high misdiagnosis rate of depressive disorder, biomarkers for the accurate diagnosis of depressive disorder are urgently needed to reduce the misdiagnosis rate and improve the cure rate. MethodsTo obtain original data, plasma samples were collected from patients suffering from various depressive disorders, including bipolar depression (BP), major depressive disorder (MDD), and persistent depressive disorder (PDD) prior to medication treatment, as well as from participants without psychiatric diagnoses (NP). Then these samples were analyzed using nano-LC–MS/MS. According to the screening criteria, differentially expressed proteins(DEPs) corresponding to different types of depressive disorders were identified, and validation proteins were identified via bioinformatics analysis and verified. ResultsNinety-nine DEPs were identified between BP and NP, 29 DEPs were identified between MDD and NP, and 14 DEPs were identified between PDD and NP. The plasma levels of PRDX2 in patients with depressive disorder were significantly increased. The plasma CRP level in BP patients was specifically increased, and the plasma SNCA level in MDD patients was specifically increased. CRP showed the best differential diagnostic ability in differentiating BP from NP, MDD and PDD, and SNCA showed the best differential diagnostic ability in differentiating MDD from NP, BP and PDD. ConclusionsThe mechanism of depressive disorder mainly involves biological processes and signaling pathways related to inflammation and lipid metabolism. The key biomarkers identified by proteomics and the signaling pathways involved are highly important for revealing the biological basis of depressive disorder and guiding its clinical diagnosis and treatment.

TMT-based quantitative proteomics analysis of defense responses induced by the Bph3 gene following brown planthopper infection in rice.

The brown planthopper (BPH) is an economically significant pest of rice. Bph3 is a key BPH resistance gene. However, the proteomic response of rice to BPH infestation, both in the presence and absence of Bph3, remains largely unexplored. In this study, we employed tandem mass tag labeling in conjunction with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to identify differentially expressed proteins (DEPs) in rice samples. We detected 265 and 125 DEPs via comparison of samples infected with BPH for 2 and 4 days with untreated samples of the BPH-sensitive line R582. For the Bph3 introgression line R373, we identified 29 and 94 DEPs in the same comparisons. Bioinformatic analysis revealed that Bph3 significantly influences the abundance of proteins associated with metabolic pathways, secondary metabolite biosynthesis, microbial metabolism in diverse environments, and phenylpropanoid biosynthesis. Moreover, Bph3 regulates the activity of proteins involved in the calcium signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and plant hormone signal transduction. Our results indicate that Bph3 enhances the resistance of rice to BPH mainly by inhibiting the down-regulation of proteins associated with metabolic pathways; calcium signaling, the MAPK signaling pathway, and plant hormone signal transduction might also be involved in BPH resistance induced by Bph3.

Insights into Medication-Induced Osteonecrosis of the Jaw Through the Application of Salivary Proteomics and Bioinformatics.

Long-term treatment with bisphosphonates is accompanied by an increased risk of medication-related osteonecrosis of the jaw (MRONJ). Currently, no clinically useful biomarkers for the predictive diagnosis of MRONJ are available. To investigate the potential key proteins involved in the pathogenesis of MRONJ, a proteomic LC-MS/MS analysis of saliva was performed. Differentially expressed proteins (DEPs) were analyzed using BiNGO, ClueGO, cytoHubba, MCODE, KEGG, and ReactomeFI software packages using Cytoscape platforms. In total, 1545 DEPs were identified, including 43 up- and 11 down-regulated with a 1.5-fold cut-off value and adj. p-value < 0.05. The analysis provided a panel of hub genes, including APOA2, APOB, APOC2, APOC3, APOE, APOM, C4B, C4BPA, C9, FGG, GC, HP, HRG, LPA, SAA2-SAA4, and SERPIND1. The most prevalent terms in GO of the biological process were macromolecular complex remodeling, protein-lipid complex remodeling, and plasma lipoprotein particle remodeling. DEPs were mainly involved in signaling pathways associated with lipoproteins, the innate immune system, complement, and coagulation cascades. The current investigation advanced our knowledge of the molecular mechanisms underlying MRONJ. In particular, the research identified the principal salivary proteins that are implicated in the onset and progression of this condition.

Combined Mendelian randomization and quantitative proteomics analysis to study the influence of thyroid dysfunction on acute ischemic stroke

AbstractAcute ischemic stroke (AIS) is characterized by high morbidity and mortality, making it crucial to identify the risk factors that influence its occurrence and prognosis. Although individuals with thyroid dysfunction exhibit altered stroke patterns, evidence from observational studies remains inconsistent. Herein, we investigated the influence of thyroid dysfunction on stroke progression and prognosis. We combined Mendelian randomization (MR) and tandem mass tag (TMT)‐based quantitative proteomics analysis to study the influence of thyroid dysfunction on AIS. Differentially expression proteins (DEPs) were subsequently identified, functional enrichment analysis was performed, and a protein–protein interaction (PPI) network was constructed. Protein alterations were further validated by western blot. MR analysis revealed a causal association between thyroid disorders and ischemic stroke. DEP analysis identified 38 downregulated proteins and five upregulated proteins. Functional enrichment analysis and PPI network construction highlighted the importance of immune response activation and acute phase pathways, along with the suppression of focal adhesion, regulation of the actin cytoskeleton, and platelet activation pathways. Vasodilator‐stimulated phosphoprotein, MYL12B, MYL6, and TPM4 were identified as key DEPs significantly associated with pathological pathways and were verified by western blot. The identification of these key proteins and pathways provides new perspectives for investigating the progression and prognosis of AIS.

Uncovering key genes associated with protein and oil in soybeans based on transcriptomics and proteomics

Soybean is an important oilseed crop, providing abundant protein and fat for human consumption. However, in practical production, there exists a significant negative correlation between soybean oil and protein content, making it difficult to obtain soybean varieties with both high protein and high oil content. There is limited research on the regulatory network governing soybean oil and protein content. We selected four soybean varieties, Sui Xiao Li (SXL), Ji Da 5 (JD5), Ji Da 33 (JD33), and Ji Yu 202 (JY202), and determined their protein and oil content. We found that SXL and JD33 are high-protein, low-oil varieties, while JD5 and JY202 are high-oil, low-protein varieties. Subsequently, transcriptomic and proteomic analyses were conducted on these four soybean varieties. The results revealed a total of 7182 differentially expressed genes (DEGs) and 1037 differentially expressed proteins (DAPs) among the four soybean varieties SXL, JD5, JD33, and JY202. Through KEGG analysis, we identified 96 and 319 DEGs involved in fatty acid metabolism and protein metabolism, respectively, as well as 23 and 28 DAPs involved in fatty acid metabolism and protein metabolism, respectively. Additionally, based on WGCNA and PPI interaction networks, several central genes were identified, which potentially play a role in the accumulation of protein content and oil content. These potential genes mainly participate in processes such as glycolysis and carbon metabolism. Joint analysis of transcriptomic and proteomic data revealed generally poor correlation between gene expression at the transcriptional and protein levels, with 240 co-regulated genes identified. Combining metabolic pathways, we identified 12 and 5 genes that are involved in lipid metabolism and protein synthesis at both transcriptional and translational levels, respectively. Finally, based on predictions of correlation and interaction, we identified 22 genes that may simultaneously regulate protein and oil content negatively at the transcriptional and translational levels. This study provides important scientific guidance for the genetic improvement of soybean quality components.