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Journal of Integrative Neuroscience Jun 2024The effects of heat acclimation (HA) on the hypothalamus after exertional heatstroke (EHS) and the specific mechanism have not been fully elucidated, and this study...
BACKGROUND
The effects of heat acclimation (HA) on the hypothalamus after exertional heatstroke (EHS) and the specific mechanism have not been fully elucidated, and this study aimed to address these questions.
METHODS
In the present study, rats were randomly assigned to the control, EHS, HA, or HA + EHS groups (n = 9). Hematoxylin and eosin (H&E) staining was used to examine pathology. Tandem mass tag (TMT)-based proteomic analysis was utilized to explore the impact of HA on the protein expression profile of the hypothalamus after EHS. Bioinformatics analysis was used to predict the functions of the differentially expressed proteins. The differential proteins were validated by western blotting. An enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines in the serum.
RESULTS
The H&E staining (n = 5) results revealed that there were less structural changes in hypothalamus in the HA + EHS group compared with the EHS group. Proteomic analysis (n = 4) revealed that proinflammatory proteins such as argininosuccinate synthetase (ASS1), high mobility group protein B2 (HMGB2) and vimentin were evidently downregulated in the HA + EHS group. The levels of interleukin (IL)-1β, IL-1, and IL-8 were decreased in the serum samples (n = 3) from HA + EHS rats.
CONCLUSIONS
HA may alleviate hypothalamic damage caused by heat attack by inhibiting inflammatory activities, and ASS1, HMGB2 and vimentin could be candidate factors involved in the exact mechanism.
Topics: Animals; Hypothalamus; Heat Stroke; Rats; Proteomics; Male; Rats, Sprague-Dawley; Physical Exertion; Disease Models, Animal
PubMed: 38940089
DOI: 10.31083/j.jin2306116 -
Journal of Integrative Neuroscience Jun 2024Perioperative neurocognitive disorders (PND) are a group of prevalent neurological complications that often occur in elderly individuals following major or emergency...
Differentially Expressed Proteins in the Serum of Elderly Patients Who Experienced Perioperative Neurocognitive Disorders Following Transurethral Resection of the Prostate.
OBJECTIVE
Perioperative neurocognitive disorders (PND) are a group of prevalent neurological complications that often occur in elderly individuals following major or emergency surgical procedures. The etiologies are not fully understood. This study endeavored to investigate novel targets and prediction methods for the occurrence of PND.
METHODS
A total of 229 elderly patients diagnosed with prostatic hyperplasia who underwent transurethral resection of the prostate (TURP) combined with spinal cord and epidural analgesia were included in this study. The patients were divided into two groups, the PND group and non-PND group, based on the Z-score method. According to the principle of maintaining consistency between preoperative and intraoperative conditions, three patients from each group were randomly chosen for serum sample collection. isobaric tags for relative and absolute quantification (iTRAQ) proteomics technology was employed to analyze and identify the proteins that exhibited differential expression in the serum samples from the two groups. Bioinformatics analysis was performed on the proteins that exhibited differential expression.
RESULTS
Among the 1101 serum proteins analyzed in the PND and non-PND groups, eight differentially expressed proteins were identified in PND patients. Of these, six proteins showed up-regulation, while two proteins showed down-regulation. Further bioinformatics analysis of the proteins that exhibited differential expression revealed their predominant involvement in cellular biological processes, cellular component formation, as well as endocytosis and phagocytosis Additionally, these proteins were found to possess the RING domain of E3 ubiquitin ligase.
CONCLUSION
The iTRAQ proteomics technique was employed to analyze the variation in protein expression in serum samples from patients with PND and those without PND. This study successfully identified eight proteins that exhibited differential expression levels between the two groups. Bioinformatics analysis indicates that proteins exhibiting differential expression are primarily implicated in the biological processes associated with microtubules. Investigating the microtubule formation process as it relates to neuroplasticity and synaptic formation may offer valuable insights for enhancing our comprehension and potential prevention of PND.
CLINICAL TRIAL REGISTRATION
Registered (ChiCTR2000028836). Date (20190306).
Topics: Humans; Male; Aged; Transurethral Resection of Prostate; Proteomics; Prostatic Hyperplasia; Neurocognitive Disorders; Postoperative Cognitive Complications; Perioperative Period; Aged, 80 and over; Blood Proteins; Computational Biology
PubMed: 38940081
DOI: 10.31083/j.jin2306123 -
Journal of Extracellular Biology Feb 2024Colon cancer is one of the most commonly occurring tumours among both women and men, and over the past decades the incidence has been on the rise. As such, the need for...
Colon cancer is one of the most commonly occurring tumours among both women and men, and over the past decades the incidence has been on the rise. As such, the need for biomarker identification as well as an understanding of the underlying disease mechanism has never been greater. Extracellular vesicles are integral mediators of cell-to-cell communication and offer a unique opportunity to study the machinery that drives disease progression, and they also function as vectors for potential biomarkers. Tumour tissue and healthy mucosal tissue from the colons of ten patients were used to isolate tissue-resident EVs that were subsequently subjected to global quantitative proteomic analysis through LC-MS/MS. In total, more than 2000 proteins were identified, with most of the common EV markers being among them. Bioinformatics revealed a clear underrepresentation of proteins involved in energy production and cellular adhesion in tumour EVs, while proteins involved in protein biosynthesis were overrepresented. Additionally, 53 membrane proteins were found to be significantly upregulated in tumour EVs. Among them were several proteins with enzymatic functions that degrade the extracellular matrix, and three of these, Fibroblast activating factor (FAP), Cell surface hyaluronidase (CEMIP2), as well as Ephrin receptor B3 (EPHB3), were validated and found to be consistent with the global quantitative results. These stark differences in the proteomes between healthy and cancerous tissue emphasise the importance of the interstitial vesicle secretome as a major player of disease development.
PubMed: 38939898
DOI: 10.1002/jex2.127 -
Frontiers in Pharmacology 2024Mesaconitine (MA), a diester-diterpenoid alkaloid extracted from the medicinal herb , is commonly used to treat various diseases. Previous studies have indicated the...
Mesaconitine (MA), a diester-diterpenoid alkaloid extracted from the medicinal herb , is commonly used to treat various diseases. Previous studies have indicated the potent toxicity of aconitum despite its pharmacological activities, with limited understanding of its effects on the nervous system and the underlying mechanisms. HT22 cells and zebrafish were used to investigate the neurotoxic effects of MA both and , employing multi-omics techniques to explore the potential mechanisms of toxicity. Our results demonstrated that treatment with MA induces neurotoxicity in zebrafish and HT22 cells. Subsequent analysis revealed that MA induced oxidative stress, as well as structural and functional damage to mitochondria in HT22 cells, accompanied by an upregulation of mRNA and protein expression related to autophagic and lysosomal pathways. Furthermore, methylated RNA immunoprecipitation sequencing (MeRIP-seq) showed a correlation between the expression of autophagy-related genes and N6-methyladenosine (m6A) modification following MA treatment. In addition, we identified METTL14 as a potential regulator of m6A methylation in HT22 cells after exposure to MA. Our study has contributed to a thorough mechanistic elucidation of the neurotoxic effects caused by MA, and has provided valuable insights for optimizing the rational utilization of traditional Chinese medicine formulations containing aconitum in clinical practice.
PubMed: 38939838
DOI: 10.3389/fphar.2024.1393717 -
Current Research in Food Science 2024Whitespotted conger () muscle proteins were susceptible to oxidative denaturation during frozen storage. The objective of this study was to investigate the alterations...
Whitespotted conger () muscle proteins were susceptible to oxidative denaturation during frozen storage. The objective of this study was to investigate the alterations in quality through physicochemical analysis and proteomics after whitespotted conger stored at temperatures of -18 °C and -60 °C. The microstructural observation revealed the noticeable variations such as increased interstitial space and fractured muscle fibre with extension of frozen storage time, and the muscle fibre of whitespotted conger stored at -60 °C were more intact than those stored at -18 °C. The raised TVB-N value indicated that the freshness of whitespotted conger decreased during 120-day frozen storage period. Analysis of myofibrillar protein content and SDS-PAGE demonstrated that compared to -18 °C, lower storage temperature (-60 °C) could better maintain the structure of whitespotted conger muscle by inhibiting protein degradation and oxidation. To reveal the mechanism of protein degradation, label-free quantitative proteomic analysis was performed through LC-MS/MS. The structural proteins including domain-associated proteins and actin-related proteins were up-regulated during frozen storage, but the phosphoglycerate kinase, phosphoglycerate mutase, and fructose-bisphosphate aldolase were down-regulated. Storage at -18 °C accelerated the up- or down-regulation of those differentially abundant proteins. According to KEGG analysis, up- or down-regulated pathways such as glycolysis/gluconeogenesis, carbon metabolism, biosynthesis of amino acids, and calcium signalling pathway mainly accounted for the protein degradation and quality reduction of whitespotted conger at low temperature. These results provided a theoretical basis for improving the quality stability of whitespotted conger during frozen storage.
PubMed: 38939611
DOI: 10.1016/j.crfs.2024.100779 -
Frontiers in Genetics 2024Breast cancer (BC), as a highly prevalent malignant tumor worldwide, is still unclear in its pathogenesis and has poor therapeutic outcomes. Alternative polyadenylation... (Review)
Review
Breast cancer (BC), as a highly prevalent malignant tumor worldwide, is still unclear in its pathogenesis and has poor therapeutic outcomes. Alternative polyadenylation (APA) is a post-transcriptional regulatory mechanism widely found in eukaryotes. Precursor mRNA (pre-mRNA) undergoes the APA process to generate multiple mRNA isoforms with different coding regions or 3'UTRs, thereby greatly increasing the diversity and complexity of the eukaryotic transcriptome and proteome. Studies have shown that APA is involved in the progression of various diseases, including cancer, and plays a crucial role. Therefore, clarifying the biological mechanisms of APA and its regulators in breast cancer will help to comprehensively understand the pathogenesis of breast cancer and provide new ideas for its prevention and treatment.
PubMed: 38939531
DOI: 10.3389/fgene.2024.1377275 -
Current Stem Cell Reports Jun 2023The underlying molecular mechanisms that direct stem cell differentiation into fully functional, mature cells remain an area of ongoing investigation. Cell state is the...
PURPOSE OF REVIEW
The underlying molecular mechanisms that direct stem cell differentiation into fully functional, mature cells remain an area of ongoing investigation. Cell state is the product of the combinatorial effect of individual factors operating within a coordinated regulatory network. Here, we discuss the contribution of both gene regulatory and splicing regulatory networks in defining stem cell fate during differentiation and the critical role of protein isoforms in this process.
RECENT FINDINGS
We review recent experimental and computational approaches that characterize gene regulatory networks, splice regulatory networks, and the resulting transcriptome and proteome they mediate during differentiation. Such approaches include long-read RNA sequencing, which has demonstrated high-resolution profiling of mRNA isoforms, and Cas13-based CRISPR, which could make possible high-throughput isoform screening. Collectively, these developments enable systems-level profiling of factors contributing to cell state.
SUMMARY
Overall, gene and splice regulatory networks are important in defining cell state. The emerging high-throughput systems-level approaches will characterize the gene regulatory network components necessary in driving stem cell differentiation.
PubMed: 38939410
DOI: 10.1007/s40778-023-00227-2 -
IScience Jun 2024Human leukocyte antigen (HLA) class-I molecules present fragments of the cellular proteome to the T cell receptor (TCR) of cytotoxic T cells to control infectious...
Human leukocyte antigen (HLA) class-I molecules present fragments of the cellular proteome to the T cell receptor (TCR) of cytotoxic T cells to control infectious diseases and cancer. The large number of combinations of HLA class-I allotypes and peptides allows for highly specific and dedicated low-affinity interactions to a diverse array of TCRs and natural killer (NK) cell receptors. Whether the divergent HLA class-I peptide complex is exclusive for interactions with these proteins is unknown. Using genome-wide CRISPR-Cas9 activation and knockout screens, we identified peptide-specific HLA-C∗07 combinations that can interact with the surface molecules CD55 and heparan sulfate. These interactions closely resemble the HLA class-I interaction with the TCR regarding both the affinity range and the specificity of the peptide and HLA allele. These findings indicate that various proteins can specifically bind HLA class-I peptide complexes due to their polymorphic nature, which suggests there are more interactions like the ones we describe here.
PubMed: 38939106
DOI: 10.1016/j.isci.2024.110120 -
Journal of Extracellular Biology Jul 2023The objectives of the present study were to determine whether obesity impacts human decidualization and the endometrial control of trophoblast invasion (both of which...
The effect of obesity on uterine receptivity is mediated by endometrial extracellular vesicles that control human endometrial stromal cell decidualization and trophoblast invasion.
The objectives of the present study were to determine whether obesity impacts human decidualization and the endometrial control of trophoblast invasion (both of which are required for embryo implantation) and evaluate the potential involvement of endometrial extracellular vesicles (EVs) in the regulation of these physiological processes. Using primary human cell cultures, we first demonstrated that obesity is associated with significantly lower in vitro decidualization of endometrial stromal cells (ESCs). We then showed that a trophoblastic cell line's invasive ability was greater in the presence of conditioned media from cultures of ESCs from obese women. The results of functional assays indicated that supplementation of the culture medium with EVs from nonobese women can rescue (at least in part) the defect in in vitro decidualization described in ESCs from obese women. Furthermore, exposure to endometrial EVs from obese women (vs. nonobese women) was associated with significantly greater invasive activity by HTR-8/SVneo cells. Using mass-spectrometry-based quantitative proteomics, we found that EVs isolated from uterine supernatants of biopsies from obese women (vs. nonobese women) presented a molecular signature focused on cell remodelling and angiogenesis. The proteomics analysis revealed two differentially expressed proteins (fibronectin and angiotensin-converting enzyme) that might be involved specifically in the rescue of the decidualization capacity in ESCs from obese women; both of these proteins are abundantly present in endometrial EVs from nonobese women, and both are involved in the decidualization process. In conclusion, our results provided new insights into the endometrial EVs' pivotal role in the poor uterine receptivity observed in obese women.
PubMed: 38939074
DOI: 10.1002/jex2.103 -
Journal of Extracellular Biology Jul 2023High-resolution computed tomography (HRCT) imaging is critical for diagnostic evaluation of Idiopathic Pulmonary Fibrosis (IPF). However, several other interstitial lung...
High-resolution computed tomography (HRCT) imaging is critical for diagnostic evaluation of Idiopathic Pulmonary Fibrosis (IPF). However, several other interstitial lung diseases (ILDs) often exhibit radiologic pattern similar to IPF on HRCT making the diagnosis of the disease difficult. Therefore, biomarkers that distinguish IPF from other ILDs can be a valuable aid in diagnosis. Using mass spectrometry, we performed proteomic analysis of plasma extracellular vesicles (EVs) in patients diagnosed with IPF, chronic hypersensitivity pneumonitis, nonspecific interstitial pneumonitis, and healthy subjects. A five-protein signature was identified by lasso regression and was validated in an independent cohort using ELISA. The five-protein signature derived from mass spectrometry data showed an area under the receiver operating characteristic curve of 0.915 (95%CI: 0.819-1.011) and 0.958 (95%CI: 0.882-1.034) for differentiating IPF from other ILDs and from healthy subjects, respectively. Stepwise backwards elimination yielded a model with 3 and 2 proteins for discriminating IPF from other ILDs and healthy subjects, respectively, without compromising diagnostic accuracy. In summary, we discovered and validated EV protein biomarkers for differential diagnosis of IPF in independent cohorts. Interestingly, the biomarker panel could also distinguish IPF and healthy subjects with high accuracy. The biomarkers need to be evaluated in large prospective cohorts to establish their clinical utility.
PubMed: 38939072
DOI: 10.1002/jex2.98