: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of ...NAFLD is less clear in China.
: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators.
: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders.
: In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.
Hundreds of pathogenic variants of mitochondrial DNA (mtDNA) have been reported to cause mitochondrial diseases, which still lack effective treatments. It is a huge challenge to install these ...mutations one by one. We repurposed the DddA-derived cytosine base editor to incorporate a premature stop codon in the mtProtein-coding genes to ablate mitochondrial proteins encoded in the mtDNA (mtProteins) instead of installing pathogenic variants and generated a library of both cell and rat resources with mtProtein depletion. In vitro, we depleted 12 of 13 mtProtein-coding genes with high efficiency and specificity, resulting in decreased mtProtein levels and impaired oxidative phosphorylation. Moreover, we generated six conditional knockout rat strains to ablate mtProteins using
system. Mitochondrially encoded ATP synthase membrane subunit 8 and NADH:ubiquinone oxidoreductase core subunit 1 were specifically depleted in heart cells or neurons, resulting in heart failure or abnormal brain development. Our work provides cell and rat resources for studying the function of mtProtein-coding genes and therapeutic strategies.
Aims
Long‐term outcome of patients after myocardial infarction (MI) largely depends on the extent of post‐infarct remodelling. To explore the molecular mechanism of remodelling, comparative proteomic ...analysis was undertaken to identify differential myocardial proteome profiles expressed in the border zone of the post‐MI heart.
Methods and results
Two‐dimensional gel electrophoresis and matrix‐assisted laser desorption/ionization tandem time‐of‐flight mass spectrometry were used to identify the differential protein profiles expressed in the border zone at specific time points (Days 0, 1, 4, and 10 post‐infarction) in a permanent rat MI model. We identified 96 differential protein spots, corresponding to 69 proteins. Cluster analysis exhibited five main temporal expression patterns corresponding to the three phases of early stage remodelling. The alteration in expression was supported by reverse transcription‐polymerase chain reaction, western blotting, and immunohistochemical analysis of three selected proteins. Bioinformatics analysis revealed that the proteins in each pattern were functionally related to specific cell processes in remodelling, such as ischaemia, inflammation, and proliferation.
Conclusion
A differential myocardial proteome profile was identified in the border zone during early stage post‐infarct remodelling. Bioinformatics analysis indicated a possible role of these proteins in remodelling. Proteomics data provided the basis for further functional study of these proteins and for identifying potential molecular targets with therapeutic anti‐remodelling effects.
Purpose
To identify biochemical markers in men with idiopathic infertility and normal sperm counts.
Experimental design
We obtained proteomic profiling proteins in human spermatozoa following ...successful or unsuccessful pregnancy via assisted reproductive technique (ART) using 6‐plex tandem mass tag (TMT) isobaric MS. Our study design consisted of two groups: (i) The semen of six men whose sperm resulted in a clinical pregnancy following ART and (ii) six men whose semen did not result in a clinical pregnancy following ART. The results of differentiated MS were validated by Western blotting.
Results and discussion
A total of 2045 proteins were detected in our cohort. Twenty‐one proteins were found to be differentially expressed (>1.2‐fold) between Group 1 and Group 2. Using the results of bioinformatics analysis and Western blotting, three proteins (A2LD1, ATP1B3, and FBXO2) were shown to have the same differential pattern (p < 0.05) that was observed in the MS analysis.
Conclusions and clinical relevance
Proteomics may help identity a select cohort of men with normal semen parameters and aid infertility diagnoses.
Huqi San (HQS) is a Chinese herbal preparation of eight medicinal herbs that promote diuresis, detoxification, blood circulation, and cholestasis. Defects in transporter expression and function can ...cause cholestasis and jaundice. However, the mechanism of the cholestasis underlying HQS effects, especially on the gastrointestinal tract ion secretion, has not been elucidated. Real-time RT-PCR and Western blotting were used to study the expression and localization of cystic fibrosis transmembrane conductance regulator (CFTR) and α-ENaC in rat alimentary tract, and then the effect of HQS on the ion transport in rat distal colon mucosa was investigated using the short-circuit current ( I SC ) technique. The results showed that pretreatment with HQS significantly enhanced mRNA transcripts and protein content of CFTR in liver and distal colon but not α-ENaC in alimentary organs. HQS increases I SC and decreases the transepithelial resistance. Pretreatment with epithelial Na+ channel blocker did not affect the I SC responses elicited by HQS, but removal of extracellular Cl− or pretreatment with Cl− channel or Na+-K+-2Cl− cotransporter blocker inhibited HQS-elicited I SC responses. These findings demonstrated that HQS, RA, and RP can stimulate Cl− secretion in the distal colon by increasing the mRNA transcripts and protein content of CFTR in liver and distal colon.
Prediabetes and its pathophysiology remain important issues. We aimed to examine the cluster characteristics of prediabetes and explore their associations with developing diabetes and its ...complications based on 12 variables representing body fat, glycemic measures, pancreatic β cell function, insulin resistance, blood lipids, and liver enzymes. A total of 55,777 individuals with prediabetes from the China Cardiometabolic Disease and Cancer Cohort (4C) were classified at baseline into six clusters. During a median of 3.1 years of follow-up, significant differences in the risks of diabetes and its complications between clusters were observed. The odds ratios of diabetes stepwisely increase from cluster 1 to cluster 6. Clusters 1, 4, and 6 have increased chronic kidney diseases risks, while the prediabetes in cluster 4, characterized by obesity and insulin resistance, confers higher risks of cardiovascular diseases compared with others. This subcategorization has potential value in developing more precise strategies for targeted prediabetes prevention and treatment.
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•Individuals with prediabetes have heterogeneity in metabolic features•Prediabetes can be classified into six subgroups with different disease risks•Prediabetes with obesity and insulin resistance has the highest CVD risk•There are specific trends of transition from prediabetes clusters to diabetes clusters
Zheng et al. use data-driven clustering approaches to confirm the heterogeneity in individuals with prediabetes and explore their associations with major diseases. Individuals with prediabetes differ in metabolic features and risks of disease progression, raising the possibility of a practical, stratified approach for the prevention of diabetes and related diseases.
The assembly of primordial follicles early in ovarian development and subsequent transition to primary follicles are critical processes in ovarian biology. Inappropriate coordination of these ...processes contributes to ovarian pathologies such as premature ovarian failure and infertility. To better understand the molecular mechanisms involved in primordial follicle assembly and development, 2-D PAGE and MALDI-TOF/TOF technologies were used to construct a comparative proteome profile of the immature rat ovary at specific time-points (0, 24, 48, and 72 h postpartum). A total of 154 differential protein spots corresponding to 134 different proteins were definitively identified between any two time-points. Further cluster analysis showed four expression patterns, and each pattern correlated with specific cell processes that occur during early ovarian development. Seven proteins were randomly selected to verify expression patterns using Western blotting, and subsequently immunohistochemistry was performed to further investigate their cellular localization. Additionally, detailed functional analyses of these differentially expressed proteins were performed. Elucidation of how these changes in protein expression level coordinate primordial follicles assembly and development is intended to provide a better understanding of these critical biological processes early in ovarian development and will provide potential therapeutic molecular targets to regulate ovarian function and treat ovarian disease.
The mature oocyte contains the full complement of maternal proteins required for fertilization, the transition to zygotic transcription, and the beginning stages of embryogenesis. Many of these ...proteins have yet to be characterized. In this study, two-dimensional electrophoresis (2-DE) of mouse metaphase-II (MII) oocyte proteins, stained with silver staining or Pro-Q Diamond dye, was performed to describe the proteome and phosphoproteome of the mouse oocyte derived from ICR mice. A total of 869 selected protein spots, corresponding to 380 unique proteins, were identified successfully by mass spectrometry, in which 90 protein spots representing 53 unique proteins have been stained with Pro-Q Diamond, indicating that they are in phosphorylated forms. All identified proteins were bioinformatically annotated in detail and compared with the embryonic stem cell (ESC) proteome. A proteome reference database for the mouse oocyte was established from the protein data generated in this study, which can be accessed over the Internet (http://reprod.njmu.edu.cn/2d). This database is the most detailed mouse oocyte proteomic database to date. It should be valuable in expanding our knowledge of the regulation of signaling in oogenesis, fertilization, and embryo development, while revealing potential mechanisms for epigenetic reprogramming.
Aim: To elucidate the anticancer mechanism of Huqi San by assessing the expression of G‐6‐Pase, SDH, ATPase and AFP in N‐nitrosodiethylamine‐mediated hepatocarcinogenesis in rats.
Methods: A ...Solt‐Farber two‐step test model of hepatocarcino genesis was established by diethylnitrosamine (DEN) and 2‐acetylaminofluorene (AAF) in rats to investigate the modifying effects of expression of 6‐glucosephosphatase (G‐6‐Pase), succinodehydrogenase (SDH), adenosine triphosphatase (ATPase) in N‐nitrosodiethylamine‐mediated hepatocarcinogenesis. Hu Qisan compounded by eight medicinal herbs was prepared in glycoprival granules with wich 0.38 g crude herbs/mL solution was prepared for administration. γ‐Glutamy‐transpeptidase (γ‐GT), G‐6‐Pase, SDH and ATPase were immunohistochemically determined. The activity of alpha‐fetoglobulin (AFP) in the livers was measured with Immunofluorescence.
Results: Huqi San treated rats showed significant decrease in areas of ‐GT positive foci (P < 0.001). On the other hand, the expression of G‐6‐Pase, SDH and ATPase has obviously altered in Huqi San treated group. The activity of AFP also significantly decreased after the treatment with Huqi San (8 g/kg body weight or 4 g/kg body weight) or total alkali of mistletoe (0.12 g/kg body weight).
Post-translational modifications (PTMs) are essential for regulating conformational changes, activities and functions of proteins, and are involved in almost all cellular pathways and processes. ...Identification of protein PTMs is the basis for understanding cellular and molecular mechanisms. In contrast with labor-intensive and time-consuming experiments, the PTM prediction using various bioinformatics approaches can provide accurate, convenient, and efficient strategies and generate valuable information for further experimental consideration. In this review, we summarize the current progresses made by Chineses bioinformaticians in the field of PTM Bioinformatics, including the design and improvement of computational algorithms for predicting PTM substrates and sites, design and maintenance of online and offline tools, establishment of PTM-related databases and resources, and bioinformatics analysis of PTM proteomics data. Through comparing similar studies in China and other countries, we demonstrate both adva
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