Protein Interaction Analysis Research Articles

Mechanistic elucidation of Ayurvedic formulation Triphala in managing gastrointestinal and neurological disorders through in silico approach

Triphala is an Ayurvedic herbal formulation used to treat gastrointestinal disorders. The present study explored the underlying mechanisms of Ayurvedic formulation Triphala against integrated gastrointestinal and neurological disorders through network pharmacology and molecular docking. Components of Triphala were screened using Dr. Duke’s Phytochemical and Ethnobotanical Database, KNApSAcK database, and Indian Medicinal Plants, Phytochemistry and Therapeutics database while target prediction was done using SuperPred 3.0, followed by mapping with shared gastrointestinal and neurological disorders targets obtained from GeneCards and DisGenet databases. STRING and Cytoscape were utilized for protein–protein and protein-target interaction analyses and further screening of core clusters. GO, KEGG, and Reactome enrichment analysis were performed, and top targets were subject to binding affinity evaluation with major Triphala compounds. Based on ADME characteristics, seven screened Triphala components overlapped with 104 genes of gastrointestinal and neurological disorders. STAT3, ESR1, HIF1A, MTOR, PPARG, MAP2K2, TLR4, SLC2A1, NFKB1, and ESR1 were revealed as major interacting nodes through protein–protein interaction, compound-target interaction, and compound-target-disease-pathway network analysis. GO enrichment indicated genes involved in managing cell response to stress, stimuli, and metabolism while KEGG enrichment revealed pathways related to cancer, metabolism, and signalling. Reactome analysis implied an enrichment of the immune system, cell signalling, and disease pathways. Thannilignan, 7-Hydroxy-3',4'-methylenedioxyflavan, and Termilignan were identified as major phytocompounds of Triphala. Molecular docking indicated excellent interactions of Triphala components with all analysed receptors with mean binding energies ranging from − 7.58 to − 8.34 kcal/mol/receptor which was most notable in the compound 7-Hydroxy-3',4'-methylenedioxyflavan. Together, this work delineates the mechanisms of Triphala and identifies new drug candidates for the integrated management of gastrointestinal and neurological disorders.

Transcriptome Analysis and Phytohormone Profile Reveal Core Phytohormone Regulating Parthenocarpy in Fingered Citron

Background: Parthenocarpy, the development of fruit without fertilization, is a significant trait in fingered citron (Citrus medica L. var. sarcodactylis Swingle). This study aims to elucidate the regulatory mechanisms underlying parthenocarpy through comparative transcriptome analysis and phytohormone profiling between fingered citron and its non-parthenocarpic counterpart, citron. Results: A total of 66 differentially expressed hormone-related genes were identified, with the auxin pathway emerging as the most prominent in fingered citron. Protein–protein interaction analysis revealed a potential interaction between auxin and abscisic acid (ABA). Phytohormone content analysis indicated that fingered citron exhibited higher levels of indole-3-acetic acid (IAA) and lower levels of ABA compared to citron. A weighted gene co-expression network analysis (WGCNA) suggested that the interplay between auxin and ABA is crucial for triggering parthenocarpy. Virus-induced gene silencing (VIGS) experiments demonstrated that silencing CmsABI5 led to decreased ABA levels, while auxin levels remained unchanged, resulting in disrupted parthenocarpy and increased ethylene levels, indicating a secondary hormonal response. Additionally, gene expression changes associated with failed parthenocarpy showed down-regulation of SAUR50 and up-regulation of PP2C 56, linking these changes to ABA signaling. Conclusions: Our findings highlight the central regulatory role of auxin in parthenocarpy in fingered citron, with ABA acting as a critical modulator. The suppression of ABA alone disrupts parthenocarpy despite stable auxin levels, emphasizing the necessity of balanced hormone interactions. This research underscores the significant role of auxin, rather than gibberellin (GA), in regulating parthenocarpy in fingered citron, contributing valuable insights to the understanding of fruit development mechanisms.

NEK2 promotes colorectal cancer progression by activating the TGF-β/Smad2 signaling pathway

Colorectal cancer (CRC) is a prevalent malignancy with poor patient survival, and NIMA-associated kinase 2 (NEK2) has been implicated in the pathogenesis and progression of various cancers, including CRC. This study aimed to investigate the impact of NEK2 on CRC cell functionality and its interaction with the TGF-β/Smad signaling pathway. NEK2 expression in CRC tissues and cell lines was assessed, and its association with patient survival was analyzed. Functional assays, including NEK2 knockdown via lentiviral infection, RT-qPCR, Western blotting, CCK-8 assay, Transwell migration, invasion assays, and goblet cell formation assays, were employed to evaluate NEK2′s effects on CRC cell proliferation, migration, invasion, and stemness. Mechanistic studies explored the TGF-β/Smad2 signaling pathway, utilizing co-immunoprecipitation (Co-IP) and protein interaction analyses. In vivo experiments further evaluated NEK2′s role in tumor initiation, metastasis, and chemoresistance. NEK2 was found to be upregulated in CRC tissues and correlated with poor survival. NEK2 knockdown inhibited CRC cell behaviors, while NEK2 activated the TGF-β/Smad2 signaling pathway through Smad2/3 phosphorylation. Overexpression of Smad2/3 reversed NEK2 knockdown effects, confirming the importance of this pathway in CRC. In vivo, NEK2 promoted tumor initiation, metastasis, and chemoresistance, effects partially reversed by Smad2/3 overexpression. These findings reveal the critical role of NEK2 in CRC progression and underscore its potential as a therapeutic target, offering new insights into the molecular mechanisms driving CRC and informing targeted therapy development.

Polystyrene Microplastics Induce Photosynthetic Impairment in Navicula sp. at Physiological and Transcriptomic Levels

The rising concentration of microplastics (MPs) in aquatic environments poses increasing ecological risks, yet their impacts on biological communities remain largely unrevealed. This study investigated how aminopolystyrene microplastics (PS-NH2) affect physiology and gene expression using the freshwater alga Navicula sp. as the test species. After exposing Navicula sp. to high PS-NH2 concentrations for 24 h, growth was inhibited, with the most significant effect seen after 48 h. Increasing PS-NH2 concentrations reduced chlorophyll content, maximum photochemical quantum yield (Fv/Fm), and the photochemical quenching coefficient (Qp), while the non-photochemical quenching coefficient (NPQ) increased, indicating a substantial impact on photosynthesis. PS-NH2 exposure, damaged cell membrane microstructures, activated antioxidant enzymes, and significantly increased malondialdehyde (MDA), glutathione peroxidase (GPX), and superoxide dismutase (SOD) activities. Transcriptomic analysis revealed that PS-NH2 also affected the gene expression of Navicula sp. The differentially expressed genes (DEGs) are mainly related to porphyrin and chlorophyll metabolism, carbon fixation in photosynthesis, endocytosis, and glycolysis/gluconeogenesis. Protein–protein interaction (PPI) analysis revealed significant interactions among DEGs, particularly within photosystem II. These findings shed insights into the toxic mechanisms and environmental implications of microplastic interactions with phytoplankton, deepening our understanding of the potential adverse effects of microplastics in aquatic ecosystems.

Enhanced photocatalytic activity, protein interaction and cost analysis studies of Carissa carandas: derived carbon quantum dots

Enhanced photocatalytic activity, protein interaction and cost analysis studies of Carissa carandas: derived carbon quantum dots

DNA nanodevice for analysis of force-activated protein extension and interactions.

Force-induced changes in protein structure and function mediate cellular responses to mechanical stresses. Existing methods to study protein conformation under mechanical force are incompatible with biochemical and structural analysis. Taking advantage of DNA nanotechnology, including the well-defined geometry of DNA origami and programmable mechanics of DNA hairpins, we built a nanodevice to apply controlled forces to proteins. This device was used to study the R1-R2 segment of the talin1 rod domain as a model protein, which comprises two alpha-helical bundles that reversibly unfold under tension to expose binding sites for the cytoskeletal protein vinculin. Electron microscopy confirmed tension-dependent protein extension while biochemical analysis demonstrated enhanced vinculin binding under tension. The device could also be used in pull down assays with cell lysates, which identified filamins as novel tension-dependent talin binders. The DNA nanodevice is thus a valuable addition to the molecular toolbox for studying mechanosensitive proteins.

RNA-Seq Analysis Uncovered Transcriptomic Changes in Poncirus trifoliata Roots Under Long-Term Soil Drought Conditions

Drought is one of the most serious abiotic stresses in citrus plantations. It is thus imperative to fully understand the drought-resistant mechanisms in these plants. Here, RNA-seq was used to analyze the transcriptomic changes in the roots of Poncirus trifoliata, a widely used rootstock in citrus plantations, under a 72-day soil drought and a 7-day recovery stage. Our results showed that the genes upregulated under drought were only enriched in the galactose metabolism and protein processing in endoplasmic reticulum pathways. In the galactose metabolism pathway, four genes related to the synthesis of raffinose family oligosaccharides, which act as osmoprotectants and ROS scavengers, were significantly upregulated under long-term drought. Several heat-shock protein (HSP) family genes were significantly upregulated under drought, leading to increased levels of HSPs to alleviate the endoplasmic reticulum-associated degradation of misfolded proteins induced by drought stress. Some other upregulated genes under drought, like late embryogenesis-abundant family genes and lipid transfer protein family genes, might also be crucial to the drought resistance of P. trifoliata roots. MSYJ196370 (heat-shock factor family gene) was the top hub gene in the protein–protein interaction analysis of upregulated genes under drought. These findings supplement the transcriptomic response of P. trifoliata root under long-term drought stress.

Luteolin-mediated phosphoproteomic changes in chicken splenic lymphocytes: Unraveling the detoxification mechanisms against ammonia-induced stress.

Long-term exposure to high ammonia concentrations could severely impact chicken health. On the other hand, luteolin has been shown to protect against ammonia poisoning. Although phosphorylation is critically involved in toxicity induction, the specific role of phosphorylated proteins in ammonia poisoning remains unclear. Herein, we constructed an in vitro model to study chicken ammonia poisoning and also analyzed the protective effects of luteolin. Specifically, a combined series of organic techniques such as protein extraction, enzyme digestion, modified peptide enrichment, Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) analysis, and bioinformatics analysis were employed for a quantitative omics study of phosphorylation modification in three groups of samples. Our findings revealed thousands of Differentially Expressed Proteins (DEPs). The differentially expressed modified proteins were subjected to GO classification, KEGG pathway analysis, cluster analysis, and protein interaction analysis, revealing the detoxification mechanism encompassed mitochondrial maintenance, signal transduction, transcriptional regulation, and cytoskeleton regulation. In the process, mitochondria and Golgi apparatus were the key organelles. Furthermore, the AKT1/FOXO signaling pathway and Heat Shock Proteins (HSPs) were the key core modifiers of the proteins. We hope that our findings will provide a theoretical basis and experimental support for future research on luteolin's detoxification mechanism against ammonia poisoning.

RNF5 exacerbates steatotic HCC by enhancing fatty acid oxidation via the improvement of CPT1A stability.

Non-alcoholic fatty liver disease (NAFLD) is expected to become the leading risk factor for liver cancer, surpassing viral hepatitis. Unlike viral hepatitis-related hepatocellular carcinoma (HCC), the role of excessive nutrient supply in steatotic HCC is not well understood, hindering effective prevention and treatment strategies. Therefore, it is crucial to identify key molecules in the pathogenesis of steatotic HCC, investigate changes in metabolic reprogramming due to excessive fatty acid (FA) supply, understand its molecular mechanisms, and find potential therapeutic targets. Trans-species transcriptome analysis identified Ring Finger Protein 5 (RNF5) as a critical regulator of steatotic HCC. RNF5 upregulation is associated with poor prognosis in steatotic HCC compared to canonical HCC. In vitro and in vivo studies showed that RNF5 exacerbates HCC in the presence of additional FA supply. Lipidomics and transcriptome analyses revealed that RNF5 significantly increases carnitine palmitoyltransferase 1A (CPT1A) mRNA levels and is positively correlated with fatty acid oxidation (FAO). Protein interaction analysis demonstrated that RNF5 promotes K63-type ubiquitination of insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1), enhancing CPT1A mRNA stabilization through m6A modification. Additionally, peroxisome proliferator-activated receptor gamma (PPARγ) was found to activate RNF5 expression specifically in HCC cells. Mechanistically, excessive exogenous FAs reorganize FA metabolism in HCC cells, worsening steatotic HCC via the PPARγ-RNF5-IGF2BP1-CPT1A axis. This study highlights a distinct FA metabolism pattern in steatotic HCC, providing valuable insights for potential therapeutic targets.

Sex-Dimorphic Differential Expression Profiles in the Brain of the Adult Chinese Soft-Shelled Turtle, Pelodiscus sinensis.

The Chinese soft-shelled turtle (Pelodiscus sinensis) is an economically important species in aquaculture, and its growth pattern is characterized by significant sexual dimorphism. However, the underlying molecular mechanisms of this phenomenon have mostly been investigated in the gonadal tissues of P. sinensis, and there are no articles on sex differentiation from the brain of P. sinensis. Here, we analyzed transcriptomes of the brains of adult male and female P. sinensis using high-throughput Illumina sequencing technology, establishing a set of differential genes and differential transcription factors. The data showed that there were 908 genes with significant differences in expression, of which 357 genes were up-regulated and 551 genes were down-regulated. We annotated using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), and screened some genes and pathways related to growth. There were 282 growth-related differential genes and 181 sex-related differential genes. We screened the genes' growth hormone receptor (GHR) and vascular endothelial growth factor A (VEGFA), which may be related to the growth of P. sinensis. The pathways related to the growth and development of P. sinensis are the growth hormone synthesis, secretion, and action pathway; the MAPK (mitogen-activated protein kinase) pathway; and the calcium signaling pathway. In addition, through gene set enrichment analysis (GSEA), we screened out two genes, LIM homeobox protein 1 (LHX1) and fibroblast growth factor 7 (FGF7), which are related to both growth and sex differentiation, and through protein interaction analysis of these genes, we screened out eight genes, including LHX1, FGF7, GHR, fibroblast growth factor 4 (FGF4), EGFR, BMP3, GLI family zinc finger 2 (GLI2), and neuronal differentiation 1 (NEUROD1), and verified the expression levels of these eight genes in the brain of the P. sinensis by real-time quantitative PCR (qRT-PCR), which supported the reliability and accuracy of our transcriptome analysis. Our study provides a solid foundation for analyzing the mechanisms of sexual-dimorphic growth of P. sinensis and even other turtles.

Full-length transcriptome sequencing of the longissimus dorsi muscle of yak and cattle-yak using nanopore technology

Short-read RNA sequencing has been used to sequence the transcriptome of the skeletal muscle of yak and cattle-yak; however, full-length transcripts cannot be obtained and alternative splicing (AS) events cannot be inferred using this sequencing approach. Here, we used Oxford Nanopore Technologies (ONT) full-length sequencing to sequence the transcriptome of the longissimus dorsi of yak and cattle-yak. A total of 20,323 novel genes and 172,870 novel transcripts were identified, and 159,700 novel transcripts were successfully annotated. A total of 157,812 AS events, 58,073 simple sequence repeats, 57,468 complete open reading frames, 2296 transcription factors, and 20,404 lncRNAs were detected. Differentially expressed transcripts (DETs) in the longissimus dorsi muscle of yak and cattle-yak were involved in the MAPK and JAK-STAT signaling pathways related to muscle development and growth. Protein–protein interaction analysis of DETs suggested that TNNI2 might make a major contribution to differences in muscle growth and meat quality traits between yak and cattle-yak. The results have enriched the transcriptome data of dorsal muscles, providing new ideas for the study of transcriptional regulation processes, and also providing useful information for the production of higher yields of yak meat.

Unveiling Genetic Basis Associated With Manganese Content in Turkish Common Bean (Phaseolus vulgaris L.) Germplasm Through a Genome‐Wide Association Study

ABSTRACTMicronutrient deficiencies, such as manganese (Mn), pose significant global health risks, affecting millions of people worldwide and leading to serious health conditions. Biofortifying crops, notably common beans, offer a sustainable solution to combat these deficiencies. This study aimed to uncover the genetic basis associated with Mn content in Turkish common bean (Phaseolus vulgaris) germplasm through a genome‐wide association study (GWAS), which is crucial for developing nutrient‐rich bean varieties. Here, we examined variation among 183 common bean accessions, collected from 19 provinces of Turkey and identified the genetic basis linked to seed Mn content. Genotype by environment interaction significantly influenced Mn content (p < 0.05). The mean Mn content was observed 31.69 mg kg−1 across the germplasm. Bingol‐16 had the lowest, while Malatya‐59 had the highest Mn contents. Stability analysis was performed using the ‘STABILITYSOFT’ method and found 10 stable accessions. The cluster constellation plot was generated using JMP statistical software. A total of 7900 DArTseq markers were used for association analysis, identifying 16 markers across four chromosomes (Pv2, Pv5, Pv7 and Pv11). Notably, markers DArT‐3374915 and DArT‐3375187 exhibited consistent associations across different environments, making them promising candidates for Mn‐focused breeding programmes. Gene annotation and interactome analysis, including BLAST searches and protein–protein interaction analysis, revealed associations of candidate genes with Mn concentration regulation, shedding light on potential mechanisms underlying Mn accumulation in common beans. Our findings lay a foundation for marker‐assisted breeding efforts in common bean improvement.

Screening Key Genes Related to Nitrogen Use Efficiency in Cucumber Through Weighted Gene Co-Expression Network Analysis.

Cucumber (Cucumis sativus L.) is a crucial vegetable crop, requiring significant nitrogen fertilizer inputs. However, excessive nitrogen application not only impairs growth but also poses severe environmental risks. Thus, enhancing nitrogen use efficiency (NUE) in cucumber is imperative. For the identification of genes associated with NUE in cucumber, roots of high NUE and low NUE lines were analyzed under high nitrogen conditions. Using transcriptome sequencing through WGCNA, a total of 15,180 genes were categorized into 35 co-expression modules, with 5 modules being highly correlated with NUE. Based on differential expression within the five modules and the results of GO and KEGG enrichment analyses, 25 genes were identified as potentially related to NUE. Among these, CsaV4_1G002492 (GLR22), CsaV4_2G003460 (GLR35), CsaV4_3G000307 (NRT1.1), and CsaV4_7G001709 (UPS2) were homologous to genes in Arabidopsis known to directly participate in NUE related process. These four genes were chosen as key genes for further analysis. qRT-PCR analysis revealed that CsaV4_3G000307 and CsaV4_7G001709 were more active during the early stages of the high nitrogen treatment in the high NUE line. Conversely, CsaV4_1G002492 and CsaV4_2G003460 were more active in the low NUE line. Using transcriptomic analysis, a frameshift INDEL mutation was observed in CsaV4_3G000307 in the low NUE line, which impacted the compactness of the protein structure, potentially altering its function. Analysis of protein interactions of these four key genes predicted some potential interaction networks. This research offers critical insights into the genetic factors influencing NUE in cucumber, presenting potential targets for genetic modification or breeding programs.

Portal hypertension as an independent risk factor for cirrhotic cardiomyopathy: An investigation on its mechanism based on bioinformatics analysis

AbstractAimsDespite being commonly found in patients with various etiologies of liver cirrhosis, cirrhotic cardiomyopathy (CCM) is often overlooked, and its mechanism remains unknown. This study aimed to illuminate the epidemiological data and risk factors of CCM and to explore its potential mechanisms through a bioinformatics analysis.MethodsClinical data were collected from January 2008 to December 2022 retrospectively, and patients were divided into the CCM and non‐CCM groups based on the criteria proposed by the 2005 World Congress of Gastroenterology. Independent risk factors for CCM were identified through a multivariate logistic regression analysis. CCM‐related genes were explored using the GeneCards database, and enrichment analysis was performed. Protein–protein interaction analysis was conducted using the Search Tool for the Retrieval of Interacting Genes (STRING) database, and hub genes were identified using Cytoscape software. The Transcriptional Regulatory Relationships Unraveled by Sentence‐based Text Mining (TRRUST) database was utilized to explore transcription factors (TFs), and a network regulatory diagram of TF‐gene pathways was constructed. Finally, potential drugs were predicted using the Drug Gene Interaction Database.ResultsA total of 965 patients with liver cirrhosis were included, among whom 563 (58.3%) were diagnosed with CCM. Portal hypertension (PHT) was identified as the only independent risk factor for CCM. The hub genes included IL6, TNF, TGFB1, IL1B, MMP9, and IL10. Enrichment analysis revealed that Forkhead box O (FoxO), mitogen‐activated protein kinase (MAPK), hypoxia‐inducible factor (HIF‐1), phosphoinositide 3‐kinase‐protein kinase B (PI3K‐AKT), interleukin (IL)‐17, tumor necrosis factor (TNF), vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR), Janus kinase/signal transducers and activators of transcription (JAK‐STAT), and transforming growth factor (TGF)‐beta pathways were enriched. TFs such as CEBPB, NFKB1, STAT1, STAT3, and SP1 were also implicated. Potential drugs included pravastatin and atorvastatin.ConclusionsThe morbidity associated with CCM was high, and PHT was the only independent risk factor. The mechanism may be related to inflammation, and statins may hold therapeutic promise.

Integrative analysis of non12‐hydroxylated bile acid revealed the suppressed molecular map of alternative pathway in nonalcoholic steatohepatitis mice

AbstractBile acids (BAs) are significantly altered in the liver and serum of patients with nonalcoholic steatohepatitis (NASH). However, the underlying mechanisms of these changes, particularly BA alternative pathways (BAP) responsible for non12‐OH BAs, remain unclear. RNA‐seq data were initially analyzed to reveal the changes of gene expression in NASH patients. Targeted metabolomics were conducted on plasma from NASH mice induced by high‐fat or western diet with CCl4 for 10–24 weeks. Liver tissues were examined using proteomics, RT‐qPCR, and western blotting. An integrated approach was then employed to analyze protein interactions and network correlations. Analysis of RNA‐seq data revealed the inhibition of CYP7B1 in NASH patients, indicating the dysregulation of BAP. In NASH mouse models, dysregulation of BA circulation was observed by increased plasma total BA (TBA) levels and decreased liver TBA, with liver swelling and histopathological changes. Targeted metabolomics revealed suppressed levels of non12‐OH BAs, which inversely correlated with increased liver injury markers. The reduced mRNA and protein expression of Fxr and upregulation of Lxr signaling in livers suggested the suppressed BAP was modulated by Fxr‐Lxr signaling. Moreover, BAP interactions predominantly implicated multiple metabolism disruptions, involving 7 hub proteins (Hk1, Acadsb, Pklr, Insr, Ldlr, Cyp27a1, and Cyp7b1), offering promising therapeutic targets for NASH. We presented the metabolic and proteomic map of BAP and its regulatory network in NASH progression. Therapeutic targeting of BAP or its co‐regulatory proteins holds promise for NASH treatment and metabolic syndrome management.

Mining autism causative SNPs based on CARMA algorithm

Abstract. Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social impairment and repetitive stereotyped behaviors. This widespread neurological disorder not only results in symptoms that affect patients' social lives, such as behavioral and social disorders, but also imposes significant mental and economic burdens on their families. Therefore, research on the causes of ASD is of great practical value and significance. Previous studies have demonstrated a high genetic association with ASD and have identified specific ASD-related genes and single nucleotide polymorphisms (SNPs). However, these studies have primarily focused on establishing correlations rather than establishing causality between specific genes, SNPs, and ASD. Therefore, this experiment utilized public data from Genome-Wide Association Studies (GWAS) and employed a novel Bayesian model called CARMA (causal robust mapping method in meta-analysis) to identify SNPs strongly correlated with ASD. Notably, this study identified 14 novel pathogenic SNPs, four of which were deemed significant. Furthermore, functional annotations were performed on the pathogenic SNPs to assess their impact on gene expression in different brain regions. This analysis revealed the cerebellum, thalamus, and substantia nigra of the midbrain as the three brain regions with the highest correlation to ASD. Additionally, protein interaction analysis was conducted, revealing GATA-4 and NKX2-2 as the genes with the strongest correlation to ASD. The findings of this study provide new insights and data for future research into the genetics and biology of ASD, particularly in the field of basic research.

Transcriptome and interactome-based analyses to unravel crucial proteins and pathways involved in Acinetobacter baumannii pathogenesis.

The present study employed an integrated transcriptome and interactome-based analyses to identify key proteins and pathways associated with Acinetobacter baumannii infection towards the development of novel therapeutics against this pathogen. Transcriptome analysis of A.baumannii strains (ATCC 17978 and AbH12O-A2) identified 253 and 619 differentially expressed genes (DEGs), respectively. These genes were involved in essential molecular functions, including DNA binding, metal ion binding, and oxidoreductase activity. The centrality and module analyses of these identified DEGs had shortlisted 27 and 41 hub proteins, which were central to the ATCC 17978 and AbH12O-A2 networks, and essential for bacterial survival. Significantly, three proteins (SecA, glutathione synthase, and aromatic-amino-acid transaminase) from the ATCC 17978 strain and seven proteins (ATP synthase subunit alpha, translation initiation factor IF-2, SecY, elongation factors G, Tu, and Ts, and tRNA guanine-N1-methyltransferase) from the AbH12O-A2 strain showed interactions with human proteins, identified through host-pathogen interaction (HPI) analysis of hub proteins (referred as hub-HPI proteins). These proteins were observed to participate in vital pathways, including glutathione metabolism, secondary metabolite biosynthesis and quorum sensing. Targeting these hub-HPI proteins through novel therapeutic strategies holds the potential to disrupt the critical bacterial pathways, thereby controlling A. baumannii infections. Furthermore, their localization analysis indicated that nine proteins were cytoplasmic and one was membrane protein. Among them, six were druggable and four were novel proteins. Overall, this comprehensive study provides valuable insights into the crucial proteins and pathways involved during A. baumannii infection, and offers potential therapeutic targets for designing novel antimicrobial agents to tackle the pathogen.

Klrb1 Loss Promotes Chronic Hepatic Inflammation and Metabolic Dysregulation.

Background/Objectives: CD161, encoded by the KLRB1 gene, is an inhibitory receptor expresses on various immune cell and has gained attention in immune checkpoint research. In recent studies, KLRB1 has been found to be one of the potential markers of liver diseases such as cirrhosis. Therefore, it will be important to understand what process KLRB1 involved in the liver for the prevention of liver diseases. Methods: We compared KO mice with wild-type controls by routine blood analysis and RNA-seq, and additionally performed H&E staining and qPCR to validate the differentially expressed genes (DEGs). Results:KO mice had fewer lymphocytes compared to the wild-type mice. A transcriptomic analysis showed that Klrb1 loss causes the upregulation of immune-related genes and pathways like NOD-like receptor and p53 signaling, while causing the downregulation of lipid metabolism-related genes. A protein interaction analysis indicated a potential cancer risk under chronic inflammation. Histological examination with H&E staining reveals an inflammatory response around the central venous vessels in the liver tissue of the KO mice. Conclusions: We conclude that Klrb1 knockout disrupts the immune and metabolic functions in the liver, which may possibly lead to chronic inflammation and malignancy risks. These findings highlight the role of Klrb1 in hepatic health.

Differential proteomic profiles of exosomes in pediatric and adult adamantinomatous craniopharyngioma cyst fluid.

Adamantinomatous craniopharyngiomas (ACPs), commonly seen in pediatrics and adults often present with large cystic cavities that can compress surrounding tissues, causing severe visual and endocrine symptoms. Complete resection of cystic ACP is challenging, frequently leading to postoperative recurrence. The composition of the cystic fluid is complex, and to date, there has been limited research focusing on exosomes within ACP cyst fluid. We collected cyst fluid from 12 ACP patients and confirmed the presence of exosomes. Subsequently, we conducted exosomal proteomic analysis using LC-MS/MS. The patients were divided into pediatric and adult groups for the analysis of differential protein enrichment, followed by comprehensive bioinformatics analysis, including GO analysis, KEGG analysis, and PPI network analysis, among other functional pathway and protein interaction analyses. Immunohistochemistry was used to determine the tissue expression distribution of the differential protein APOA1. In our data analysis, 64 significantly differentially expressed proteins were identified, with 37 being overexpressed in the pediatric group and 27 in the adult group. Our results revealed that exosomal proteins in the pediatric group were predominantly enriched in modules and pathways related to high-density lipoprotein particle, apolipoprotein receptor binding, and the PPAR signaling pathway. Additionally, APOA1, as the hub protein with the highest connectivity in the differential protein interaction network, may play a critical role in β-amyloid metabolism pathways in pediatric ACP. This study is the first to construct a proteomic map of ACP cyst fluid exosomes, suggesting significant differences in the tumor microenvironment's lipid metabolism between pediatrics and adults.

Causal effects of plasma proteome on intervertebral disc degeneration: a comprehensive mendelian randomization study.

Intervertebral disc degeneration (IVDD) considerably impacts global disability and quality of life. Although potential links between plasma proteins and IVDD exist, their causal correlation remains undefined. This study explored the causal links between plasma proteins and IVDD employing genome-wide association study data. For this observational study, summary statistics for plasma proteins were derived from an Icelandic population, paralleled with genome-wide data on IVDD obtained from the FinnGen consortium. Using two-sample Mendelian randomization, we assessed the causal relationship between 4,907 plasma proteins and IVDD. Standard sensitivity analyses encompassing heterogeneity, pleiotropy, and leave-one-out cross-validation tests confirmed the stability and robustness of the findings. Subsequently, through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein interaction analyses, we delved into the functional interrelation among identified plasma proteins. A causal association with IVDD was identified for 47 plasma proteins; myoneurin, intersectin 1, and eukaryotic translation initiation factor 4 gamma 3 maintained significant correlations post multiple correction tests (P < 1.02 × 10- 5), influencing IVDD development positively. GO/KEGG pathway analyses confirmed that multiple pathways may be involved in IVDD development. The study underscores the causal correlation between plasma protein levels and IVDD risk. These identified proteins could emerge as unique biomarkers for IVDD, contributing to its predictive measures. The findings further our understanding of IVDD pathomechanisms and prospective therapeutic targets.