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The Pathogenesis of Psoriasis Vulgaris Mediated by Gut Microbiota-Host Co-Metabolism Regulating Tryptophan Metabolic Pathway
No full textBackground: Psoriasis vulgaris (PV) is one of the most common chronic inflammatory skin diseases, but its exact etiology and pathological mechanism are not fully understood. The regulation of tryptophan metabolism by gut microbiota-host co-metabolism has been confirmed to significantly affect the pathogenesis of various chronic inflammatory and autoimmune diseases. Tryptophan and its main metabolites are partly involved in the pathogenesis and progression of psoriasis, but its specific regulatory mechanism has not yet been clarified. The purpose of this study is to explore the changes in the intestinal flora and its metabolic characteristics in PV patients. Methods: 16S rRNA sequencing combined with metabolomics was used to explore changes in gut microbiota and its metabolic characteristics. Alpha, Beta diversity and LEfSe (Linear Discriminant Analysis Effect Size) analyses were used to analyze the changes in the intestinal flora and to screen biomarkers. PCA (Principal Component Analysis) and OPLS-DA (Orthogonal Partial Least Squares-Discriminant Analysis) methods were used to analyze the differences in metabolite composition. PICRUS (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) software was used to predict metabolic function. Results: The result revealed differences in the tract microbiota composition between normal and psoriasis patients, suggesting that microbial populations may mediate the development of psoriasis. Fecal metabolite profiles revealed distinct metabolites associated with the psoriasis samples group (PSG). These products of metabolism primarily participated in metabolic pathways including amino acid biosynthesis, carbohydrate degradation and glycolysis. There is a positive/negative correlation between these gut microbes and metabolites. Conclusions: The results suggest that the gut microbiota and its metabolites may play a crucial role in the development of PSG, which may provide a potential biomarker for the treatment of PSG
Grape Seed Proanthocyanidin Extract Alleviates Atherosclerosis by Modulating the Production of Trimetlylamine N-Oxide
No full textBackground: Trimetlylamine N-oxide (TMAO) is an important factor in the development of atherosclerosis. Research suggests that grape seed proanthocyanidin extract (GSPE) modulates gut microbiota and alleviates obesity. Therefore, we speculate that GSPE may alleviate atherosclerosis by regulating TMAO production. This study aims to explore the effect of GSPE on the TMAO content and atherosclerosis. Methods: A high fat diet mice model was established for performing this study. Low-dose/high-dose GSPE (GSPE-L/GSPE-H) and Atorvastatin (Ato) were used to treat the mice for 6 weeks. The body weight, fat, blood glucose, and blood lipid of the mice were recorded and compared. The plaques and pathological changes of mouse aorta were observed by Oil Red O, Hematoxylin-Eosin and Masson staining. Serum and caecal contents of mice were collected, where TMAO level was assessed by enzyme-linked immunosorbent assay (ELISA) and gut microbial content was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Results: GSPE-H down-regulated blood glucose and blood lipid levels, and reduced aortic plaque generation and atherosclerotic damage in model mice (p < 0.05). More importantly, it reduced the TMAO content in the serum of model mice and regulated the gut microbial content (p < 0.05). The therapeutic effect of GSPE-H was similar to that of Ato. Conclusions: GSPE-H alleviates atherosclerosis by reducing production of TMAO
MicroRNA-216a-5p Regulates Hashimoto’s Thyroiditis by Targeting KIAA0101
No full textBackground: MicroRNAs (miRNA) are biomarkers and potential therapeutic targets for autoimmune diseases, including Hashimoto’s thyroiditis (HT). However, there are limited studies to evaluate the mechanism of microRNAs associated with HT. This study explores the mechanism of action and anti-inflammation activity of miR-216a-5p in thyroid follicular epithelial cells. Methods: In this research, 100 ng/mL LPS (lipopolysaccharide) was used to induce Nthy-ori 3-1 cells to simulate HT in vitro, and then the cell activity and cytotoxicity were measured using CCK-8 (Cell Counting Kit-8) and flow cytometry. The KIAA0101 and miR-216a-5p expressions in the thyroid follicular epithelial cells and HT patients were measured by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and western blot assay. Luciferase activity was used to characterize the interaction between miR-216a-5p and KIAA010. In addition, the ability of thyroid follicular epithelial cells to secrete inflammatory factors was measured using an enzyme-linked immunosorbent assay (ELISA) kit. Results: The expression of miR-216a-5p was abnormally down-regulated in the lipopolysaccharide (LPS)-induced thyroid follicular epithelial cells and the thyroid gland of HT patients. Down-regulation of miR-216a-5p severely inhibited the proliferation activity of cells, induced apoptosis, and enhanced the inflammatory response. In addition, LPS significantly up-regulated KIAA0101 expression (p < 0.05) in HT patients. miR-216a-5p overexpression substantially inhibited KIAA0101 expression due to the existence of binding sites between miR-216a-5p and KIAA0101, enhanced cell proliferation, inhibited apoptosis and exerted anti-inflammatory activity. Furthermore, its overexpression significantly reduced the level of inflammatory factors such as tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL-1β) (p < 0.05). Conclusions: miR-216a-5p could bind with KIAA0101 and regulate KIAA0101 to achieve effective therapy for Hashimoto’s thyroiditis
A Cancer-Associated Fibroblast Prognostic Signature in Hepatocellular Carcinoma
No full textBackground: Although the number of therapies for hepatocellular carcinoma has increased, the survival rate is still unsatisfactory. Cancer-associated fibroblasts have been reported to regulate hepatocellular carcinoma progression via various mechanisms. We aimed to investigate an effective prognostic tool related to cancer-associated fibroblasts for decision-making in patients with hepatocellular carcinoma. Methods: Bioinformatics analyses were used to identify cancer- and fibroblast-associated genes based on data from the Cancer Genome Atlas and Gene Expression Omnibus datasets. Following Cox and least absolute shrinkage and selection operator analyses, the optimal prognostic genes were identified, and a prognostic cancer-associated fibroblast signature was established based on these genes. Receiver operator characteristic analysis was used to validate the performance of the signature. In addition, the correlation between the cancer-associated fibroblast signature and clinical, immune, and mutational features was analyzed. Finally, a prognostic nomogram was developed and evaluated. Results: Six cancer- and fibroblast-associated prognostic genes (PZP (pregnancy zone protein), TSPYL5 (testis-specific protein Y-encoded-like 5), ADAMTSL2 (a disintegrin and metalloproteinase with thrombospondin motifs like 2), SAMD12 (sterile alpha motif domain containing 12), PNMA2 (paraneoplastic Ma antigens family member 2), and N4BP3 (NEDD4 binding protein 3)) in hepatocellular carcinoma were identified to construct the cancer-associated fibroblast risk score. The receiver operating characteristic curve showed that the signature exhibited good performance in predicting the survival of patients with hepatocellular carcinoma (with an area under the curve >0.75). Furthermore, the low-risk group showed better stromal and immune scores and a lower tumor mutation burden. Finally, a nomogram model was constructed to predict the survival of hepatocellular carcinoma patients. Conclusions: This study shows a promising cancer-associated fibroblast signature that might be useful in predicting the survival and personalized management of patients with hepatocellular carcinoma in the clinic
Exploration of Potential Biomarkers and Mechanisms for COVID-19 and Asthma Based on Microarray Analysis
No full textAims: The aim of this study is to investigate the potential mechanisms of coronavirus disease (COVID-19) and asthma comorbidities. Methods: GSE147507 and GSE143303 datasets were obtained from the Gene Expression Omnibus (GEO) database, the differential expressed genes (DEGs) were identified, and the overlapping DEGs were obtained by determining the DEG intersection between the two datasets. A series of analyses of the shared DEGs were performed, including enrichment analysis, protein-protein interaction (PPI) network construction, construction of transcription factor (TF)/microRNA (miRNA)-gene interaction networks, drug-gene and disease-gene interactions, and receiver operating characteristic curve (ROC) analysis. Results: A total of 135 overlapping DEGs were obtained by determining the DEGs intersection between the GSE147507 and GSE143303 datasets. These overlapped DEGs were significantly enriched in the regulation of DNA-templated transcription, initiation, clathrin-sculpted gamma-aminobutyric acid transport vesicle, DNA binding, and eight KEGG (kyoto encyclopedia of genes and genomes) pathways. The PPI network revealed that HSPA8, SRSF1, NDUFAB1, PTEN, CCT8, HIST1H2BK, HIST2H2BE, DLAT, EIF3G, and WAC, with high scores, were the hub genes. In addition, 65 TFs (transcription factors) and 369 miRNAs targeted overlapping DEGs. Finally, these overlapped DEGs were also related to other diseases, such as hyperglycemia, metabolic acidosis, and lung neoplasm, and the top 10 drugs with the most significant potential included lanatoside C, digoxin, GW-8510, doxorubicin, daunorubicin, proscillaridin, anisomycin, helveticoside, ouabain, and bisacodyl. The ROC analysis results shown that these hub genes had good diagnostic performance. Conclusions: HSPA8, SRSF1, NDUFAB1, PTEN, CCT8, HIST1H2BK, HIST2H2BE, DLAT, EIF3G, WAC, FOXC1, GATA2, hsa-miR-93-5p, and hsa-miR-17-5p may play vital roles in COVID-19 (corona virus disease-2019)/asthma comorbidity. Lanatoside C, digoxin, GW-8510, doxorubicin, daunorubicin, proscillaridin, anisomycin, helveticoside, ouabain, and bisacodyl may serve as drug targets against COVID-19/asthma comorbidity
NAT10 Promotes the Malignant Progression of Hepatocellular Carcinoma through Upregulating RelA/p65 Acetylation
No full textPurposes: N-acetyltransferase 10 (NAT10), a newly discovered specific N-acetyl transferase, plays a vital role in human disease. However, its role in the malignant progression of hepatocellular carcinoma (HCC) has not been fully elucidated. Methods: We first investigated the expression of NAT10 in HCC and the correlation between the expression of NAT10 and patient prognosis by using multiple groups of clinical tissues combined with data from The Cancer Genome Atlas (TCGA) database. We next constructed stable cell lines from HCC cells to confirm the tumor-promoting effects of NAT10 in HCC. In addition, we conducted various molecular experiments combined with mass spectrometry and transcriptome sequencing were conducted to further explore the internal molecular mechanism of NAT10 enhancing the HCC malignant process. Results: We found that NAT10 expression was markedly elevated in HCC tissues and the elevated levels of NAT10 were associated with worse prognoses in HCC patients. Cell function experiments showed that NAT10 overexpression enhanced HCC cell proliferation and migration, implying that NAT10 promoted the malignant progression of HCC. Furthermore, a sorafenib killing experiment showed that knocking out NAT10 enhanced the drug sensitivity of Hep3B cells. In addition, after overexpression of NAT10 in SMMC-7721 cells, the cells were significantly more resistant to sorafenib. Our study also showed that NAT10 activated the nuclear factor-kappa B (NF-κB) signaling pathway by directly binding RelA/p65 to promote lysine 310 acetylation. Moreover, NAT10 promoted HCC proliferation by promoting acetyl-NF-κB p65 (Lys310) in vivo and in vitro. Conclusions: Our study showed that NAT10 promoted the occurrence and development of HCC, which provides a corresponding theoretical basis for subsequent related research and translational application
Bibliometric Analysis and Scientific Knowledge Map Study of the Current Situation and Development Trend of the Treatment Related to Autoimmune Thyroid Disease
No full textBackground: Autoimmune thyroid disease (AITD) is a prevalent autoimmune endocrine disease, affecting approximately 5% of the population. The literature related to AITD has been increasing annually. Therefore, we conducted a bibliometric analysis of this literature to gain an intuitive understanding of the research frontiers and development trends in this field. Methods: To investigate autoimmune thyroid disease literature published from December 1, 2007 to March 27, 2023, we retrieved data from the Web of Science Core Collection (WOSCC) database, limiting the search to English literature. We then used CiteSpace 6.2.R2 and VOSviewer 1.6.18 software to analyze annual publications, countries/regions, institutions, journals, authors, literature co-citation analysis, and collaborative network analysis of keywords in the AITD field. Results: The study collected 1095 articles from 72 countries, with the majority published by the United States and Italy. The number of publications related to autoimmune thyroid disease has been increasing annually, reaching its peak in 2020. The main research institutions are the University of Pisa, Harvard University, University of Messina, and UDICE-French Research Universities. The most frequently cited journals are “J CLIN ENDOCR METAB” (791 times) and “AIDS READ” (791 times), and the journal with the most published papers is “THYROID” (Q1, impact factor 6.506, published 38 papers, accounting for 16.17% of the total literature). These publications come from 479 authors, with Antonelli Alessandro, Fallahi Poupak, Ferrari Silvia Martina, Smith Terry J, and Benvenga Salvatore publishing the most papers. The co-occurrence of keywords indicates research hotspots. Early research directions focused on Graves disease, autoimmune thyroid disease, Hashimotos thyroiditis, and management. With the appearance of emerging vocabulary such as monoclonal antibody, selenium supplementation, orbital fibroblasts, and Teprotumumab, researchers became more interested in the pathogenesis, risk factors, and clinical treatment of AITD, and conducted deeper research. Conclusions: This study utilized data information mining and visualization software to analyze the current research status in the field of AITD. The study identified the hotspots of recent research and aimed to provide a theoretical basis for future research. The research findings can help researchers gain insight into the progress of AITD research and quickly determine new directions for future research
Thymus Algeriensis and Artemisia Herba-Alba Essential Oils: Cytotoxicity, Antibacterial and Antifungal Activities and Subacute Toxicity
No full textBackground: Bacterial resistance to antibiotics and cancer cells resistance to chemotherapeutic drugs are two major public health issues. Thymus algeriensis Boiss. & Reut. and Artemisia herba-alba Asso are two common medicinal plants used to combat several pathologies, including bacterial infections and different types of cancer. This study aims to assess the cytotoxic, antibacterial and antifungal activities of each single essential oil and their combination in vitro and in silico. Methods: The cytotoxicity was evaluated in vitro towards three cell lines: liver human hepatocyte carcinoma cell line, metastatic adenocarcinoma Michigan Cancer Foundation-7, and Anderson-Metastatic Breast 231. Antibacterial activity was tested by the disc diffusion method on three bacterial and two fungal strains. The subacute oral toxicity was performed to assess the potential toxicity of the studied Essential Oils (EOs) followed by an analysis of the blood biochemical parameters. Lastly, docking studies were performed to assess the antimicrobial effect of Thymol, Chrysanthenone, Camphor and Borneol. Results: The results of the cytotoxicity test showed that there is a good dose-effect correlation between the essential oils and their mixture for the range of concentrations tested (0–50 μg/mL). However, the mixture induced a greater antiproliferative effect compared to the two oils tested separately against the three cell lines. The antibacterial and antifungal activities have revealed that the essential oil of Thymus (T.) algeriensis has an interesting antibacterial and antifungal activity against Bacillus subtilis and Penicillium digitatum with complete inhibition at 3.125 and 6.25 μg/mL, respectively. Similarly, Staphylococcus (S.) aureus had a very high sensitivity to the essential oil of Artemisia (A.) herba-alba with an inhibitory concentration of 3.125 μg/mL, as well as potent activity against Candida albicans and Penicillium digitatum, which were inhibited at 6.250 μg/mL. The subacute toxicity results showed no toxic effects in mice treated with the essential oils mixture (150 mg/kg) compared to the control group (p < 0.05). The molecular docking showed that thymol exhibited the highest activity among the molecules studied. Conclusions: These studies show that the essential oils of T. algeriensis and A. herba-alba have great antiproliferative power important synergistic effect, and good antibacterial and antifungal activities
Effects of Intermittent Fasting on Blood Sugar and Serum Metabolomics of High-Fat Diet-Induced Obesity Mice
No full textBackground: Intermittent fasting (IF) has a broad spectrum of benefits for obesity and related metabolic disorders. However, serum metabolic signatures from IF remain relatively unexplored, and it remains uncertain whether different IF approaches exert similar effects on metabolism. This study was designed to examine the effects of three distinct IF approaches time-restricted feeding (TRF), alternate-day fasting (ADF), and intermittent fasting 5:2 (IF 5:2)-on the serum metabolomics of obesity mice. Methods: Male C57BL/6 mice were placed on either a normal-fat diet (NFD) or a high-fat diet (HFD) for 10 weeks. The HFD-fed mice were subsequently subjected to dietary intervention using ADF, TRF, and IF 5:2 for another 10 weeks. Parameters such as body weight, serum lipid levels, homeostasis model assessment of insulin resistance (HOMA-IR), and glucose tolerance were assessed in each group. Hepatic lipid accumulation and pathological changes were examined using Oil Red O staining and hematoxylin and eosin (H&E) staining. Quantitative real-time PCR (qRT-PCR) was used to analyze the expression of inflammatory factors. The impact of IF on serum metabolites was investigated through non-targeted metabolomics based on UHPLC-HRMS/MS. Results: ADF, TRF, and IF 5:2 led to a significant reduction in body weight (p < 0.01), HOMA-IR (p < 0.01), and serum lipids level (p < 0.05) while also improving glucose tolerance in obese mice. All three IF approaches reduced hepatic lipid accumulation and decreased inflammation levels in adipose tissues of obese mice. Serum metabolomics analysis revealed 209 differential metabolites affected by IF. Pathway enrichment analysis identified 8 relevant pathways involved in IF. Conclusions: ADF, TRF, and IF 5:2 diets could attenuate obesity, hyperglycemia, insulin resistance, and inflammation induced by HFD. Furthermore, IF improved the serum metabolic patterns in obese mice
The Mechanism of Qishen Yixin Granules in Suppressing Myocardial Fibrosis: A Pharmacological Validation Based on Network Pharmacology
No full textBackground: Myocardial fibrosis (MF) is a condition that plays a crucial role in heart failure (HF) development and death, and current drugs for its treatment are limited. Qishen Yixin Granule (QSYXG) is a Traditional Chinese Medicine (TCM) that has been shown to be effective in treating chronic HF, but its mechanism of action is not yet fully understood. This study aimed to reveal the molecular mechanisms and bioactive compounds of QSYXG treating MF using an integrated network pharmacology and pharmacological validation pathway. Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, drug-target database and GeneCard database were used to screen active ingredients, drug targets and MF genes. The clusterProfiler package in R programming language was employed for functional and pathway enrichment analyses. Experimental validation was completed using hematoxylin-eosin staining, Massons trichrome staining, and immunohistochemistry in isoproterenol-induced MF rats. Western blot, phalloidin staining, and immunofluorescence staining were performed to elucidate the predicted mechanism on H9C2 cells. Results: In this study, 55 bioactive components and 59 putative targets were collected. Functional enrichment analysis revealed that responses to lipopolysaccharides, oxidative stress, and hypoxia constituted vital biological processes. Six targets, containing mitogen-activated protein kinase (MAPK) 14, prostaglandin-endoperoxide synthase 2 (PTGS2), serine/threonine kinase 1 (AKT1), MAPK8, Interleukin (IL)-6 and IL-1β, directly regulated these responses simultaneously. Five pathways were identified by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. QSYXG could downregulate the expression of PTGS2, MAPK14 and MAPK8 and upregulate the expression of AKT1 in the treatment of MF. Conclusions: This study revealed that QSYXG could alleviate MF based on multiple components, targets and pathways