Atherosclerosis, gut microbiome, and exercise in a meta-omics perspective: a literature review.

Background: Cardiovascular diseases are the leading cause of death worldwide, significantly impacting public health. Atherosclerotic cardiovascular diseases account for the majority of these deaths, with atherosclerosis marking the initial and most critical phase of their pathophysiological progression. There is a complex relationship between atherosclerosis, the gut microbiome's composition and function, and the potential mediating role of exercise. The adaptability of the gut microbiome and the feasibility of exercise interventions present novel opportunities for therapeutic and preventative approaches. Methodology: We conducted a comprehensive literature review using professional databases such as PubMed and Web of Science. This review focuses on the application of meta-omics techniques, particularly metagenomics and metabolomics, in studying the effects of exercise interventions on the gut microbiome and atherosclerosis. Results: Meta-omics technologies offer unparalleled capabilities to explore the intricate connections between exercise, the microbiome, the metabolome, and cardiometabolic health. This review highlights the advancements in metagenomics and metabolomics, their applications in research, and examines how exercise influences the gut microbiome. We delve into the mechanisms connecting these elements from a metabolic perspective. Metagenomics provides insight into changes in microbial strains post-exercise, while metabolomics sheds light on the shifts in metabolites. Together, these approaches offer a comprehensive understanding of how exercise impacts atherosclerosis through specific mechanisms. Conclusions: Exercise significantly influences atherosclerosis, with the gut microbiome serving as a critical intermediary. Meta-omics technology holds substantial promise for investigating the gut microbiome; however, its methodologies require further refinement. Additionally, there is a pressing need for more extensive cohort studies to enhance our comprehension of the connection among these element.

Bibliometric analysis of METTL3: Current perspectives, highlights, and trending topics.

N6-methyladenosine (m6A) is a representative of RNA methylation modification, which plays a critical role in the epigenetic modification process of regulating human diseases. As a key protein for m6A, methyltransferase 3 (METTL3) had been identified to be associated with a variety of diseases. The publications related to METTL3 were searched in the Web of Science Core Collection from the earliest mention to July 1st, 2022. Being screened by the retrieval strategy, a total of 1,738 articles related to METTL3 were retrieved. Much of our work focused on collecting the data of annual publication outputs, high-yielding countries/regions/authors, keywords, citations, and journals frequently published for qualitative and quantitative analysis. We found that diseases with high correlations to METTL3 not only included various known cancers but also obesity and atherosclerosis. In addition to m6A-related enzyme molecules, the most frequent key molecules were MYC proto-oncogene (C-MYC), Enhancer of zeste homolog 2 (EZH2), and Phosphatase and tensin homolog deleted on chromosome 10 (PTEN). METTL3 and methyltransferase 14 (METTL14) may function through opposite regulatory pathways in the same disease. "Leukemia," "Liver Cancer," and "Glioblastoma" were speculated to be potential hotspots in METTL3 related study. The number of publications had significantly surged year by year, demonstrating the growing importance of the research on epigenetic modification in the pathology of various diseases.

Global Trends of Lipid Metabolism Research in Epigenetics Field: A Bibliometric Analysis from 2012-2021.

Most common diseases are characterized by metabolic changes, among which lipid metabolism is a hotspot. Numerous studies have demonstrated a strong correlation between epigenetics and lipid metabolism. This study of publications on the epigenetics of lipid metabolism searched in the Web of Science Core Collection from 2012 to 2022, and a total of 3685 publications were retrieved. Much of our work focused on collecting the data of annual outputs, high-yielding countries and authors, vital journals, keywords and citations for qualitative and quantitative analysis. In the past decade, the overall number of publications has shown an upward trend. China (1382, 26.69%), the United States (1049, 20.26%) and Italy (206, 3.98%) were the main contributors of outputs. The Chinese Academy of Sciences and Yale University were significant potential cooperation institutions. Articles were mainly published in the "International Journal of Molecular Sciences". In addition to typical liver-related diseases, "ferroptosis", "diabetes" and "atherosclerosis" were identified as potential research topics. "NF-κB" and "oxidative stress" were referred to frequently in publications. METTL3 and ALKBH5 were the most discussed m6A-related enzymes in 2022. Our study revealed research hotspots and new trends in the epigenetics of lipid metabolism, hoping to provide significant information and inspiration for researchers to further explore new directions.

A systematic pan-cancer analysis of the gasdermin (GSDM) family of genes and their correlation with prognosis, the tumor microenvironment, and drug sensitivity.

Background: Pyroptosis is a programmed cell death process mediated by the gasdermin (GSDM) protein. However, limited research has been conducted to comprehensively analyze the contribution of the GSDM family in a pan-cancer setting. Methods: We systematically evaluated the gene expression, genetic variations, and prognostic values of the GSDM family members. Furthermore, we investigated the association between the expression of GSDM genes and immune subtypes, the tumor microenvironment (TME), the stemness index, and cancer drug sensitivities by means of a pan-cancer analysis. Results: GSDM genes were highly upregulated in most of the tested cancers. Low-level mutation frequencies within GSDM genes were common across the examined types of cancer, and their expression levels were associated with prognosis, clinical characteristics, TME features, and stemness scores in several cancer types, particularly those of the urinary system. Importantly, we found that the expressions of GSDMB, GSDMC, and GSDMD were higher in kidney carcinomas, and specifically kidney renal clear cell carcinoma (KIRC); which adversely impacted the patient outcome. We showed that GSDMD was potentially the most useful biomarker for KIRC. The drug sensitivity analysis demonstrated that the expressions of GSDM genes were correlated with the sensitivity of tumor cells to treatment with chemotherapy drugs nelarabine, fluphenazine, dexrazoxane, bortezomib, midostaurin, and vincristine. Conclusion: GSDM genes were associated with tumor behaviors and may participate in carcinogenesis. The results of this study may therefore provide new directions for further investigating the role of GSDM genes as therapeutic targets in a pan-cancer setting.

Expression of airway smooth muscle contractile proteins in children with acute interstitial pneumonia.

The purpose of the present study was to investigate the expression of α-SMA and SM22α in airway smooth muscle (ASM) of bronchioles from children younger than 14 years who died of acute interstitial pneumonia (AIP). This is based upon the hypothesis that as contractile marker proteins α-SMA and SM22α can serve as an index of the overcontractile phenotype of ASM that is seen in AIP. Lung tissue samples of children were obtained from autopsies and divided into the AIP group (55.9% male and 44.1% female, between 0.4 and 132 months old, n = 34) and the control group (60% male and 40% female, between 2 and 156 months old, n = 10). We recorded the post-mortem interval (PMI), height, clinical symptoms and abdominal fat thickness (AFT) of each case. Haematoxylin-and-eosin-stained sections were used to examine the luminal area and observe the morphological changes in the bronchioles. Immunohistochemistry and Masson's trichrome staining were used to detect the expression of contractile marker proteins and the degree of pulmonary fibrosis respectively. Compared with the control group, the luminal areas of bronchioles in the AIP group were smaller (p < .001). The expression differences in α-SMA and SM22α between the two groups were statistically significant (p = .01 and p = .02 respectively). Also, there was no significant correlation of the contractile marker proteins expression with PMI, height, clinical symptoms and AFT. The collagen deposition difference in lung between the two groups was not statistically significant (p = .224). These findings suggest that enhancement of ASM contractile function appears to be involved in the death mechanism of children with AIP, which affords more insights into the understanding of AIP.

The genomic history of southwestern Chinese populations demonstrated massive population migration and admixture among proto-Hmong-Mien speakers and incoming migrants.

Southwest China was the crossroad for the initial settler people of East Asia, which shows the highest diversity in languages and genetics. This region played a significant role in the formation of the genetic makeup of the proto-Hmong-Mien-speaking people and in the north-to-south human expansion during the Neolithic-to-historic transformation. Their genetic history covering migration events and the admixture processes still needs to be further explored. Therefore, in the current study, we have generated genome-wide data from three genomic aspects covering autosomal, mitochondrial and Y-chromosomal regions in 260 Hmong-Mien, Tibeto-Burman, and Sinitic people from 29 different southwestern Chinese groups, and further analyzed them with 2676 published modern and ancient Eurasian genomes. Here, we have noticed a new southwestern East Asian genetic cline composed of the Hmong-Mien-specific ancestry enriched in modern Hmong and Pathen. This newly identified southern inland East Asian lineage contributed to a great extent of the gene pool in the modern southern East Asians. We also have observed genetic substructure among Hmong-Mien-speaking populations. The southern Hmong-Mien-speaking people showed more genetic affinity with modern Tai-Kadai/Austroasiatic people, while the northern Hmong-Mien speakers expressed a closer genetic connection with the Neolithic-to-modern northern East Asians. Moreover, southwestern Sinitic populations had a strong genomic affinity with the adjacent Hmong-Mien-speaking populations and the lowlander Tibeto-Burman-speaking populations, which suggested the large-scale genetic admixture occurred between them. Allele-sharing-based qpAdm/qpGraph results further confirmed that all included southwestern Chinese populations could be modeled as a mixed result of the major ancestry component from the northern millet farmers in the Yellow River basin and the minor ancestry component from the southern rice farmers in the Yangtze River basin. Usually, this newly identified Hmong-Mien-associated southern East Asian ancestry could improve our understanding of the full-scale genetic landscape of the evolutionary and admixture history of southwestern East Asians. Further ancient genomic studies from southeastern China are required to shed deeper light on our established phylogeny context.

Genomic history and forensic characteristics of Sherpa highlanders on the Tibetan Plateau inferred from high-resolution InDel panel and genome-wide SNPs.

Sherpa people, one of the high-altitude hypoxic adaptive populations, mainly reside in Nepal and the southern Tibet Autonomous Region. The genetic origin and detailed evolutionary profiles of Sherpas remain to be further explored and comprehensively characterized. Here we analyzed the newly-generated InDel genotype data from 628 Dingjie Sherpas by merging with 4222 worldwide InDel profiles and collected genome-wide SNP data (approximately 600K SNPs) from 1612 individuals in 191 modern and ancient populations to explore and reconstruct the fine-scale genetic structure of Sherpas and their relationships with nearby modern and ancient East Asians based on the shared alleles and haplotypes. The forensic parameters of 57 autosomal InDels (A-InDels) included in our used new-generation InDel amplification system showed that this focused InDel panel is informative and polymorphic in Dingjie Sherpas, suggesting that it can be used as the supplementary tool for forensic personal identification and parentage testing in Dingjie Sherpas. Descriptive findings from the PCA, ADMIXTURE, and TreeMix-based phylogenies suggested that studied Nepal Sherpas showed excess allele sharing with neighboring Tibeto-Burman Tibetans. Furthermore, patterns of allele sharing in f-statistics demonstrated that Nepal Sherpas had a different evolutionary history compared with their neighbors from Nepal (Newar and Gurung) but showed genetic similarity with 2700-year-old Chokhopani and modern Tibet Tibetans. QpAdm/qpGraph-based admixture sources and models further showed that Sherpas, core Tibetans, and Chokhopani formed one clade, which could be fitted as having the main ancestry from late Neolithic Qijia millet farmers and other deep ancestries from early Asians. Chromosome painting profiles and shared IBD fragments inferred from fineSTRUCTURE and ChromoPainter not only confirmed the abovementioned genomic affinity patterns but also revealed the fine-scale genetic microstructures among Sino-Tibetan speakers. Finally, natural-selection signals revealed via iHS, nSL and iHH12 showed natural selection signatures associated with disease susceptibility in Sherpas. Generally, we provided the comprehensive landscape of admixture and evolutionary history of Sherpa people based on the shared alleles and haplotypes from the InDel-based genotype data and high-density genome-wide SNP data. The more detailed genetic landscape of Sherpa people should be further confirmed and characterized via ancient genomes or single-molecule real-time sequencing technology.

DNA Methylation Regulator-Meditated Modification Patterns Define the Distinct Tumor Microenvironment in Lung Adenocarcinoma.

BACKGROUND: Epigenetic changes of lung adenocarcinoma (LUAD) have been reported to be a relevant factor in tumorigenesis and cancer progression. However, the molecular mechanisms responsible for DNA methylation patterns in the tumor immune-infiltrating microenvironment and in cancer immunotherapy remain unclear. METHODS: We conducted a global analysis of the DNA methylation modification pattern (DMP) and immune cell-infiltrating characteristics of LUAD patients based on 21 DNA methylation regulators. A DNA methylation score (DMS) system was constructed to quantify the DMP model in each patient and estimate their potential benefit from immunotherapy. RESULTS: Two DNA methylation modification patterns able to distinctly characterize the immune microenvironment characterization were identified among 513 LUAD samples. A lower DMS, characterized by increased CTLA-4/PD-1/L1 gene expression, greater methylation modifications, and tumor mutation burden, characterized a noninflamed phenotype with worse survival. A higher DMS, characterized by decreased methylation modification, a greater stromal-relevant response, and immune hyperactivation, characterized an inflamed phenotype with better prognosis. Moreover, a lower DMS indicated an increased mutation load and exhibited a poor immunotherapeutic response in the anti-CTLA-4/PD-1/PD-L1 cohort. CONCLUSION: Evaluating the DNA methylation modification pattern of LUAD patients could enhance our understanding of the features of tumor microenvironment characterization and may promote more favorable immunotherapy strategies.

Fine-Scale Genetic Structure and Natural Selection Signatures of Southwestern Hans Inferred From Patterns of Genome-Wide Allele, Haplotype, and Haplogroup Lineages.

The evolutionary and admixture history of Han Chinese have been widely discussed via traditional autosomal and uniparental genetic markers [e.g., short tandem repeats, low-density single nucleotide polymorphisms). However, their fine-scale genetic landscapes (admixture scenarios and natural selection signatures) based on the high-density allele/haplotype sharing patterns have not been deeply characterized. Here, we collected and generated genome-wide data of 50 Han Chinese individuals from four populations in Guizhou Province, one of the most ethnolinguistically diverse regions, and merged it with over 3,000 publicly available modern and ancient Eurasians to describe the genetic origin and population admixture history of Guizhou Hans and their neighbors. PCA and ADMIXTURE results showed that the studied four populations were homogeneous and grouped closely to central East Asians. Genetic homogeneity within Guizhou populations was further confirmed via the observed strong genetic affinity with inland Hmong-Mien people through the observed genetic clade in Fst and outgroup f 3 /f 4-statistics. qpGraph-based phylogenies and f 4-based demographic models illuminated that Guizhou Hans were well fitted via the admixture of ancient Yellow River Millet farmers related to Lajia people and southern Yangtze River farmers related to Hanben people. Further ChromoPainter-based chromosome painting profiles and GLOBETROTTER-based admixture signatures confirmed the two best source matches for southwestern Hans, respectively, from northern Shaanxi Hans and southern indigenes with variable mixture proportions in the historical period. Further three-way admixture models revealed larger genetic contributions from coastal southern East Asians into Guizhou Hans compared with the proposed inland ancient source from mainland Southeast Asia. We also identified candidate loci (e.g., MTUS2, NOTCH4, EDAR, ADH1B, and ABCG2) with strong natural selection signatures in Guizhou Hans via iHS, nSL, and ihh, which were associated with the susceptibility of the multiple complex diseases, morphology formation, alcohol and lipid metabolism. Generally, we provided a case and ideal strategy to reconstruct the detailed demographic evolutionary history of Guizhou Hans, which provided new insights into the fine-scale genomic formation of one ethnolinguistically specific targeted population from the comprehensive perspectives of the shared unlinked alleles, linked haplotypes, and paternal and maternal lineages.

Significant East Asian Affinity of the Sichuan Hui Genomic Structure Suggests the Predominance of the Cultural Diffusion Model in the Genetic Formation Process.

The ancestral origin and genomic history of Chinese Hui people remain to be explored due to the paucity of genome-wide data. Some evidence argues that an eastward migration of Central Asians gave rise to modern Hui people, which is referred to as the demic diffusion hypothesis; other evidence favors the cultural diffusion hypothesis, which posits that East Asians adopted Muslim culture to form the modern culturally distinct populations. However, the extent to which the observed genetic structure of the Huis was mediated by the movement of people or the assimilation of Muslim culture also remains highly contentious. Analyses of over 700 K SNPs in 109 western Chinese individuals (49 Sichuan Huis and 60 geographically close Nanchong Hans) together with the available ancient and modern Eurasian sequences allowed us to fully explore the genomic makeup and origin of Hui and neighboring Han populations. The results from PCA, ADMIXTURE, and allele-sharing-based f-statistics revealed a strong genomic affinity between Sichuan Huis and Neolithic-to-modern Northern East Asians, which suggested a massive gene influx from East Asians into the Sichuan Hui people. Three-way admixture models in the qpWave/qpAdm analyses further revealed a small stream of gene influx from western Eurasians into the Sichuan Hui people, which was further directly confirmed via the admixture event from the temporally distinct Western sources to Sichuan Hui people in the qpGraph-based phylogenetic model, suggesting the key role of the cultural diffusion model in the genetic formation of the Sichuan Huis. ALDER-based admixture date estimation showed that this observed western Eurasian admixture signal was introduced into the Sichuan Huis during the historic periods, which was concordant with the extensive western-eastern communication along the Silk Road and historically documented Huis' migration history. In summary, although significant cultural differentiation exists between Hui people and their neighbors, our genomic analysis showed their strong genetic affinity with modern and ancient Northern East Asians. Our results support the hypothesis that the Sichuan Huis arose from a mixture of minor western Eurasian ancestry and predominant East Asian ancestry.