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1.
Phytomedicine ; 129: 155645, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38643714

RESUMO

BACKGROUND: Qing-Yi Recipe, a classic traditional Chinese medicine (TCM), is widely used for treating acute diseases of the abdomen, especially pancreatitis, the efficacy of which has been demonstrated in more than thirty clinical trials. However, the in-vivo pharmacodynamic material basis for this formula remains unclear. METHODS: A sensitive and accurate method for quantifying twenty-two potential bioactive constituents of Qing-Yi Recipe in biological samples was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and this method was fully validated. Then, the integrated pharmacokinetic properties of Qing-Yi Recipe and its major metabolites in rats were investigated using the post-listed granules at both dosages. Subsequently, tissue distributions of those constituents in nine organs (especially the pancreas) were determined, and the overall parameters between the two formulations were compared. RESULTS: Though the chemical profiles of the formulas varied across formulations, the overall exposure level was very similar, and baicalin, wogonoside, geniposide, rhein, costunolide, and paeoniflorin were the top six bioactive compounds in the circulation. All twenty-two natural products reached their first peak within 2 h, and several of them exhibited bimodal or multimodal patterns under the complicated transformation of metabolic enzymes, and the parameters of these products markedly changed compared with those of monomers. Diverse metabolites of emodin and baicalin/baicalein were detected in circulation and tissues, augmenting the in vivo forms of these compounds. Finally, the enrichment of tetrahydropalmatine and corydaline in the pancreas were observed and most compounds remained in the gastrointestinal system, providing a foundation basis for their potential regulatory effects on the gut microbiota as well as the intestinal functions. CONCLUSION: Herein, the pharmacokinetic properties and tissue distribution of multiple potential active constituents in Qing-Yi Recipe were investigated at two dosages, providing a pharmacodynamic material basis of Qing-Yi Recipe for the first time. This investigation is expected to provide a new perspective and reference for future studies on the physiological disposition and potential pharmacodynamic basis of traditional Chinese medicine to treat acute abdomen diseases.


Assuntos
Medicamentos de Ervas Chinesas , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Animais , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/química , Masculino , Espectrometria de Massas em Tandem/métodos , Distribuição Tecidual , Ratos , Cromatografia Líquida/métodos , Medicina Tradicional Chinesa
2.
Int J Biol Macromol ; 266(Pt 1): 131083, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38531519

RESUMO

Owing to the powerful affinity of tannin toward heavy metal ions, it is frequently immobilized on adsorbents to enhance their adsorption properties. However, natural adsorbents containing tannin have been overlooked owing to its water solubility. Herein, a novel natural adsorbent based on the immature persimmon residue (IPR) with soluble tannin removed was fabricated to eliminate Pb(II) and Cr(VI) in aquatic environments. The insoluble tannin in IPR endowed it with prosperous properties for eliminating Pb(II) and Cr(VI), and the IPR achieved maximum Pb(II) and Cr(VI) adsorption quantities of 68.79 mg/g and 139.40 mg/g, respectively. Kinetics and isothermal adsorption analysis demonstrated that the removal behavior was controlled by monolayer chemical adsorption. Moreover, the IPR exhibited satisfactory Pb(II) and Cr(VI) removal efficiencies even in the presence of multiple coexisting ions and showed promising regeneration potential after undergoing five consecutive cycles. Additionally, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) analysis unveiled that the elimination mechanisms were primarily electrostatic attraction, chelation and reduction. Overall, the IPR, as a tannin-containing biosorbent, was verified to possess substantial potential for heavy metal removal, which can provide new insights into the development of novel natural adsorbents from the perspective of waste resource utilization.


Assuntos
Cromo , Diospyros , Chumbo , Águas Residuárias , Poluentes Químicos da Água , Purificação da Água , Cromo/química , Cromo/isolamento & purificação , Águas Residuárias/química , Chumbo/química , Adsorção , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação , Diospyros/química , Purificação da Água/métodos , Cinética , Taninos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Concentração de Íons de Hidrogênio
3.
Chin Med ; 19(1): 29, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383512

RESUMO

BACKGROUND: Postoperative ileus (POI) is a common obstruction of intestinal content passage caused by almost all abdominal operations that seriously strokes the quality of life of patients. Kuanchang-Shu granule (KCSG), a classic modified prescription based on "Da-Cheng-Qi Decoction", has obtained satisfactory efficacy in the clinical therapeutics of POI. However, its material basis and holistic molecular mechanism against POI have not been revealed. METHODS: The chemical ingredients of KCSG were first characterized by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). Subsequently, an integration strategy of the network pharmacology and molecular docking based on above identified ingredients was performed to unveil the potential targets involved in the treatment of KCSG on POI. Finally, intestinal manipulation induced rat POI model was constructed to verify the efficacy and predicted mechanism of KCSG against POI. RESULTS: In total, 246 ingredients mainly including organic acids, flavonoids, quinones, alkaloids, terpenoids, phenylpropanoids and phenols were identified. 41 essential ingredients, 24 crucial targets as well as 15 relevant signaling pathways were acquired based on network pharmacology analysis. Pharmacodynamic research showed that KCSG treatment could protect intestinal histological damage, promote the recovery of measurement of gastrointestinal transit disorder and inhibit the secretion of myeloperoxidase in the distal ileum tissues. The up-regulated expression of p-AKT and down-regulated expression of p-eNOS and HSP9OAA1 predicted by molecular docking and validated by western blotting showed that AKT/eNOS/HSP90AA1 pathway may be one of the crucial mechanisms that mediates the protective effect of KCSG.

4.
Life Sci ; 339: 122422, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38224815

RESUMO

As a potent pro-angiogenic factor, the role of CD93 in the prognosis and therapeutic outcomes of lung squamous cell carcinoma (LUSC) merits exploration. In this study, we systematically collected transcriptomic, genomic, and clinical data from various public databases, as well as pathological images from hospital-operated patients. Employing statistical analysis software like R (Version 4.2.2) and GraphPad (Version 8.0), we conducted comprehensive analyses of multi-omics data. The results revealed elevated CD93 expression in LUSC tissues, closely associated with various cancer-related pathways. High CD93 expression indicated advanced clinical stage and poorer prognosis. Furthermore, CD93 contributed to resistance against chemotherapy and immunotherapy by enhancing tumor cell stemness, reducing immune cell infiltration, and inducing T cell exhaustion. Patients with low CD93 expression exhibited higher response rates to both chemotherapy and immunotherapy. Immunohistochemistry validated the significance of CD93 in LUSC. CD93 emerges as a biomarker signaling unfavorable prognosis and influencing therapeutic outcomes, suggesting a potential LUSC treatment avenue.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Pulmão , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Prognóstico
5.
Int J Biol Macromol ; 261(Pt 1): 129584, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38246443

RESUMO

Disulfidptosis, a recently identified mode of cellular demise marked by excess SLC7A11-reliant cystine, has been proved to affect the development and resilience of tumor cells through the production of glutathione from cystine. Glutathione synthesis plays a crucial role in chemotherapy resistance and the survival of liver cancer cells. Thus, understanding the relationship between disulfidptosis and hepatocellular carcinoma (HCC) is imperative. A molecular typing approach was employed to classify patients with HCC into two distinct subtypes, namely disulfidptosis and disulfide-homeostasis, based on the expression of genes associated with disulfidptosis. Patients with disulfidptosis exhibited a longer survival time, improved immune status, and heightened sensitivity to conventional chemotherapeutic drugs and immunotherapy. Patients with disulfide-homeostasis demonstrated an immunosuppressive microenvironment, drug resistance, and unfavorable prognosis. A prognostic model was constructed utilizing the significant prognostic variables of the disulfidptosis-regulated genes. A real-world cohort was subjected to multiplex immunofluorescence to validate the clinical outcomes and immune context. Ultimately, our study delved into the prognostic relevance of disulfidptosis in HCC and provides insights into potential avenues for future research.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Cistina , Microambiente Tumoral/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Dissulfetos , Glutationa
6.
Int J Biol Macromol ; 257(Pt 2): 128616, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38070815

RESUMO

Persimmon tannins, particularly in immature persimmons, haven't yet received corresponding attention to research on therapy of diabetes mellitus in spite of high hypoglycemic activity. To accurately screening key hypoglycemic components, immature persimmon extracts were isolated and identified using enzyme affinity ultrafiltration and HRLC-ESI-MS/MS. Among them, Hederagenin (IC50 = 0.077 ± 0.003 mg/mL), Ursolic acid (IC50 = 0.001 ± 0.000 mg/mL) and Quercetin dehydrate (IC50 = 0.081 ± 0.001 mg/mL) exhibited the strongest inhibitory effect on α-amylase (HSA and PPA) and α-glucosidase, respectively. And their inhibition mechanisms were analyzed using multi-spectral analysis, atomic force microscope and molecular docking, indicating the bonding with starch digestion enzymes through hydrogen bonding and hydrophobic interaction, and generating the enzyme aggregation. In vivo starch-tolerance experiment further verified that these inhibitors could improve postprandial hyperglycemia (17.18 % âˆ¼ 40.29 %), far more than acarbose. Suppressing, Hederagenin and Ursolic acid as triterpenoids appeared amazing potentiality to alleviate postprandial hyperglycemia, which suggested that IPE were comprehensive exploration values on prevention and treatment of hyperglycemia.


Assuntos
Diospyros , Hiperglicemia , Ácido Oleanólico/análogos & derivados , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Diospyros/química , alfa-Glucosidases , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Simulação de Acoplamento Molecular , alfa-Amilases , Espectrometria de Massas em Tandem , Amido , Inibidores de Glicosídeo Hidrolases/farmacologia
7.
Pharmacol Res ; 199: 107006, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38000562

RESUMO

Gallbladder and biliary diseases (GBDs) are one of the most common digestive diseases. The connections between GBDs and several organs other than the liver have gradually surfaced accompanied by the changes in people's diet structure and the continuous improvement of medical diagnosis technology. Among them, cholecardia syndrome that takes the heart as the important target of GBDs complications has been paid close attention. However, there are still no systematic report about its corresponding clinical manifestations and pathogenesis. This review summarized recent reported types of cholecardia syndrome and found that arrhythmia, myocardial injury, acute coronary syndrome and heart failure are common in the general population. Besides, the clinical diagnosis rate of intrahepatic cholestasis of pregnancy (ICP) and Alagille syndrome associated with gene mutation is also increasing. Accordingly, the underlying pathogenesis including abnormal secretion of bile acid, gene mutation, translocation and deletion (JAG1, NOTCH2, ABCG5/8 and CYP7A1), nerve reflex and autonomic neuropathy were further revealed. Finally, the potential treatment measures and clinical medication represented by ursodeoxycholic acid were summarized to provide assistance for clinical diagnosis and treatment.


Assuntos
Síndrome de Alagille , Colestase Intra-Hepática , Complicações na Gravidez , Feminino , Gravidez , Humanos , Síndrome de Alagille/complicações , Síndrome de Alagille/diagnóstico , Síndrome de Alagille/genética , Colestase Intra-Hepática/complicações , Colestase Intra-Hepática/tratamento farmacológico , Ácido Ursodesoxicólico/uso terapêutico
8.
J Proteomics ; 288: 104996, 2023 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-37657719

RESUMO

Unexplained recurrent spontaneous abortion (URSA) seriously affects female reproductive health, causing a great burden to patients both physically and mentally. Endometrial decidualization plays an important role in pregnancy, and impaired decidualization is an essential cause of URSA, but the cause of the damage is still poorly understood. This study aimed to reveal the pathogenesis of URSA by analyzing the differential protein expression profiles in the decidual tissue of patients with recurrent abortion compared to those with normal pregnancy. Morphological analysis revealed abnormal decidualization of endometrial tissue in patients with URSA. Quantitative proteomics analysis showed that a total of 146 differentially expressed proteins were identified between the two groups, among which 95 proteins were downregulated and 51 proteins were upregulated. Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed that the protein expression profile and signaling pathways of endometrium in patients with URSA changed significantly, and cytoskeleton remodeling and morphological transformation disorders were associated with abortion induced by incomplete decidualization. Meanwhile, transcription factors analysis showed that the 3 most affected families were zf-C2H2, MYB and HMG. Therefore, our study may provide a basis for searching for potential markers of decidualization injury. SIGNIFICANCE: At present, there are still about 50% of RSA patients with unknown causes, which brings great difficulties and blindness to clinical diagnosis and treatment.The limited proteomic studies on URSA further contribute to the lack of understanding in this field. However, in this study, the focus was on proteomic profiling analysis of the human endometrium in URSA patients compared to normal women. The findings revealed that cytoskeletal remodeling disorder is a significant contributor to the failure of decidualization in URSA patients. This insight highlights the potential role of cytoskeleton-related proteins in the pathogenesis of URSA, providing valuable information for further research and potential therapeutic interventions.


Assuntos
Aborto Habitual , Proteômica , Gravidez , Humanos , Feminino , Aborto Habitual/genética , Aborto Habitual/patologia , Endométrio , Transdução de Sinais , Reprodução
9.
BMC Cancer ; 23(1): 549, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37322434

RESUMO

BACKGROUND: Immune-related genes (IRGs) have been confirmed to play an important role in tumorigenesis and tumor microenvironment formation in hepatocellular carcinoma (HCC). We investigated how IRGs regulates the HCC immunophenotype and thus affects the prognosis and response to immunotherapy. METHODS: We investigated RNA expression of IRGs and developed an immune-related genes-based prognostic index (IRGPI) in HCC samples. Then, the influence of the IRGPI on the immune microenvironment was comprehensively analysed. RESULTS: According to IRGPI, HCC patients are divided into two immune subtypes. A high IRGPI was characterized by an increased tumor mutation burden (TMB) and a poor prognosis. More CD8 + tumor infiltrating cells and expression of PD-L1 were observed in low IRGPI subtypes. Two immunotherapy cohorts confirmed patients with low IRGPI demonstrated significant therapeutic benefits. Multiplex immunofluorescence staining determined that there were more CD8 + T cells infiltrating into tumor microenvironment in IRGPI-low groups, and the survival time of these patients was longer. CONCLUSIONS: This study demonstrated that the IRGPI serve as a predictive prognostic biomarker and potential indicator for immunotherapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Imunoterapia , Prognóstico , Linfócitos T CD8-Positivos , Microambiente Tumoral/genética
10.
J Transl Med ; 21(1): 150, 2023 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-36829199

RESUMO

INTRODUCTION: Alterations in the MET gene, including amplifications and exon 14 skipping mutations, have been identified as actionable oncogenic alterations. However, MET fusions are rarely detected in lung cancer, and their sensitivity to therapeutics has not been systematically analyzed. METHODS: The data from 30876 lung cancer patients from the LAVA database and 7966 patients from cBioPortal database were screened. Basic demographic and clinical information for the patients harboring MET fusions were collected. A lung squamous cell cancer patient harboring a novel EML4-MET fusion was treated with crizotinib. Additionally, a literature review was performed to summarize the cases of patients harboring MET fusions and their treatment information. RESULTS: MET fusions were found in only 0.2% to 0.3% of lung cancer patients and appeared in almost all exons of the MET gene. Intragenic MET fusions were found in 52.6% (41/78) of the included patients. Crizotinib was effective for MET fusions, including a novel identified EML4-MET fusion, even after the failure of multiple lines of treatment. This result suggested that acquired MET fusions become more regionally selective, as they usually occurred in exons encoding the extracellular region. Interestingly, the MET-fused genes in primary MET fusions or acquired MET fusions were very different, which indicated the different functions and influences of the disease. CONCLUSION: MET fusions are rare, and half of the fusion types were intragenic fusions. Lung cancer patients harboring primary or acquired MET fusions could benefit from crizotinib. In addition, EML4-MET was first reported in this study as a novel MET fusion type.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Crizotinibe/uso terapêutico , Neoplasias Pulmonares/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Oncogenes , Inibidores de Proteínas Quinases/farmacologia , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/uso terapêutico , Mutação
11.
J Ethnopharmacol ; 306: 116089, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-36621660

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Pueraria Flos (PF), a traditional herbal medicine, is botanically from the dried flowers of Pueraria lobate (Willd.) Ohwi. (Chinese: ) or Pueraria thomsonii Benth. (Chinese: ). It has a long history of thousands of years in China for awakening the spleen, clearing the lungs, relieving alcohol. AIM OF THE REVIEW: This review aims to report the up-to-date research progress in ethnopharmacology, phytochemistry, pharmacology and toxicology, metabolism and therapeutic application of PF, so as to provide a strong basis for future clinical treatment and scientific research. MATERIALS AND METHODS: Relevant information on PF was collected from scientific literature databases including PubMed, CNKI and other literature sources (Ph.D. and M.Sc. dissertations and Chinese herbal classic books) by using the keyword "Puerariae". RESULTS: Briefly, phytochemical research report has isolated 39 flavonoids, 19 saponins and 25 volatile oils from PF. Flavonoids and saponins are the most important bioactive compounds, and most of the quality control studies focus on these two types of compounds. Modern pharmacological studies have revealed their significant biological activities in relieving alcoholism, hepatoprotective, anti-tumor, anti-inflammatory, and anti-oxidation, which provides theoretical support for the traditional use. CONCLUSIONS: Comprehensive analysis showed that pharmacological activity of most purified compounds from PF had not been reported. Kakkalide, tectoridin and their deglycosylated metabolites (irisolidone and tectorigenin) has been focused on excessively due to their higher content and better activities. This leads to low development and resources waste. Interestingly, PF made a breakthrough in the field of food. Many kinds of fat-lowering foods such as PILLBOX Onaka have been popular in Japan market, which received extensive attention. Therefore, we suggest that future research can be paid attention on the development of the plant's function in the field of food and medicine, as well as the transformation from experimental to clinical.


Assuntos
Medicamentos de Ervas Chinesas , Pueraria , Saponinas , Pueraria/química , Etnofarmacologia , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/análise , Flores/química , Saponinas/análise , Compostos Fitoquímicos/farmacologia , Medicina Tradicional Chinesa
12.
Chin J Integr Med ; 29(1): 52-60, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36401750

RESUMO

OBJECTIVE: To investigate the anti-invasion efficacy of the ethanol extract of Oldenlandia diffusa Will. (EEOD) on a three-dimensional (3D) human malignant glioma (MG) cell invasion and perfusion model based on microfluidic chip culture and the possible mechanism of action of Oldenlandia diffusa Will. (OD). METHODS: The comprehensive pharmacodynamic analysis method in this study was based on microfluidic chip 3D cell perfusion culture technology, and the action mechanism of Chinese medicine (CM) on human MG cells was investigated through network pharmacology analysis. First, the components of EEOD were analyzed by ultraperformance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Then, cell viability and apoptosis were assessed to determine the optimum concentration of EEOD for invasion experiments, and two-dimensional (2D) migration and invasion abilities of U87 and U251 MG cells were evaluated using scratch wound and Transwell assays. The possible mechanism underlying the effects of EEOD on glioma was analyzed through a network pharmacology approach. RESULTS: Thirty-five compounds of EEOD were detected by UPLC-Q-TOF/MS. EEOD suppressed the viability of MG cells, promoted their apoptosis, and inhibited their migratory and invasive potentials (all P<0.05). Network pharmacology analysis showed that OD inhibited the invasion of MG cells by directly regulating MAPK and Wnt pathways through MAPK, EGFR, MYC, GSK3B, and other targets. The anti-invasion effect of OD was also found to be related to the indirect regulation of microtubule cytoskeleton organization. CONCLUSIONS: ]EEOD could inhibit the invasion of human MG cells, and the anti-invasion mechanism of OD might be regulating MAPK and Wnt signaling pathways and microtubule cytoskeleton organization.


Assuntos
Medicamentos de Ervas Chinesas , Glioma , Oldenlandia , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Glioma/tratamento farmacológico , Microfluídica , Farmacologia em Rede , Oldenlandia/química , Extratos Vegetais/farmacologia
13.
Front Pharmacol ; 13: 982893, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339607

RESUMO

When coronavirus disease 2019 (COVID-19) develops into the severe phase, lung injury, acute respiratory distress syndrome, and/or respiratory failure could develop within a few days. As a result of pulmonary tissue injury, pathomorphological changes usually present endothelial dysfunction, inflammatory cell infiltration of the lung interstitium, defective gas exchange, and wall leakage. Consequently, COVID-19 may progress to tremendous lung injury, ongoing lung failure, and death. Exploring the treatment drugs has important implications. Recently, the application of traditional Chinese medicine had better performance in reducing fatalities, relieving symptoms, and curtailing hospitalization. Through constant research and study, plant polysaccharides may emerge as a crucial resource against lung injury with high potency and low side effects. However, the absence of a comprehensive understanding of lung-protective mechanisms impedes further investigation of polysaccharides. In the present article, a comprehensive review of research into plant polysaccharides in the past 5 years was performed. In total, 30 types of polysaccharides from 19 kinds of plants have shown lung-protective effects through the pathological processes of inflammation, oxidative stress, apoptosis, autophagy, epithelial-mesenchymal transition, and immunomodulation by mediating mucin and aquaporins, macrophage, endoplasmic reticulum stress, neutrophil, TGF-ß1 pathways, Nrf2 pathway, and other mechanisms. Moreover, the deficiencies of the current studies and the future research direction are also tentatively discussed. This research provides a comprehensive perspective for better understanding the mechanism and development of polysaccharides against lung injury for the treatment of COVID-19.

14.
Front Pharmacol ; 13: 915535, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110520

RESUMO

Puerariae Flos, a representative homology plant of medicine and food for alcoholism, has a long history of clinical experience and remarkable curative effect in the treatment of alcoholic liver disease (ALD). However, its effective forms and hepatoprotective mechanisms remain unknown. In the present study, a strategy based on UPLC-QTOF MS combined with mass defect filtering technique was established for comprehensive mapping of the metabolic profile of PF in rat plasma, urine, bile, and feces after oral administration. Furthermore, the absorbed constituents into plasma and bile with a relatively high level were subjected to the network analysis, functional enrichment analysis, and molecular docking to clarify the potential mechanism. Finally, the therapeutic effect of PF on ALD and predicted mechanisms were further evaluated using a rat model of alcohol-induced liver injury and Western blot analysis. In total, 25 prototype components and 82 metabolites, including 93 flavonoids, 13 saponins, and one phenolic acid, were identified or tentatively characterized in vivo. In addition, glucuronidation, sulfation, methylation, hydroxylation, and reduction were observed as the major metabolic pathways of PF. The constructed compound-target-pathway network revealed that 11 absorbed constituents associated with the 16 relevant targets could be responsible for the protective activity of PF against ALD by regulating nine pathways attributable to glycolysis/gluconeogenesis, amino acid metabolism, and lipid regulation as well as inflammation and immune regulation. In addition, four active ingredients (6″-O-xylosyltectoridin, genistein-7-glucuronide-4'-sulfate, tectoridin-4'-sulfate, and 6″-O-xylosyltectoridin-4'-sulfate) as well as two target genes (MAO-A and PPAR-α) were screened and validated to play a crucial role with a good molecular docking score. The present results not only increase the understanding on the effective form and molecular mechanisms of PF-mediated protection against ALD but also promote better application of PF as a supplement food and herbal medicine for the treatment of ALD.

15.
World J Gastroenterol ; 28(20): 2152-2162, 2022 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-35721881

RESUMO

Given the breakthroughs in key technologies, such as image recognition, deep learning and neural networks, artificial intelligence (AI) continues to be increasingly developed, leading to closer and deeper integration with an increasingly data-, knowledge- and brain labor-intensive medical industry. As society continues to advance and individuals become more aware of their health needs, the problems associated with the aging of the population are receiving increasing attention, and there is an urgent demand for improving medical technology, prolonging human life and enhancing health. Digestive system diseases are the most common clinical diseases and are characterized by complex clinical manifestations and a general lack of obvious symptoms in the early stage. Such diseases are very difficult to diagnose and treat. In recent years, the incidence of diseases of the digestive system has increased. As AI applications in the field of health care continue to be developed, AI has begun playing an important role in the diagnosis and treatment of diseases of the digestive system. In this paper, the application of AI in assisted diagnosis and the application and prospects of AI in malignant and benign digestive system diseases are reviewed.


Assuntos
Aprendizado Profundo , Gastroenteropatias , Inteligência Artificial , Gastroenteropatias/diagnóstico , Gastroenteropatias/terapia , Humanos , Redes Neurais de Computação
17.
Bioinformatics ; 38(6): 1560-1567, 2022 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-34935928

RESUMO

MOTIVATION: Kernel-based association test (KAT) has been a popular approach to evaluate the association of expressions of a gene set (e.g. pathway) with a phenotypic trait. KATs rely on kernel functions which capture the sample similarity across multiple features, to capture potential linear or non-linear relationship among features in a gene set. When calculating the kernel functions, no network graphical information about the features is considered. While genes in a functional group (e.g. a pathway) are not independent in general due to regulatory interactions, incorporating regulatory network (or graph) information can potentially increase the power of KAT. In this work, we propose a graph-embedded kernel association test, termed gKAT. gKAT incorporates prior pathway knowledge when constructing a kernel function into hypothesis testing. RESULTS: We apply a diffusion kernel to capture any graph structures in a gene set, then incorporate such information to build a kernel function for further association test. We illustrate the geometric meaning of the approach. Through extensive simulation studies, we show that the proposed gKAT algorithm can improve testing power compared to the one without considering graph structures. Application to a real dataset further demonstrate the utility of the method. AVAILABILITY AND IMPLEMENTATION: The R code used for the analysis can be accessed at https://github.com/JialinQu/gKAT. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Algoritmos , Simulação por Computador , Fenótipo
18.
Chin Med ; 16(1): 143, 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34952619

RESUMO

Traditional Chinese medicines are an important class of natural products mainly derives from animals, plants and minerals, most of which need to be improved and processed before clinical use due to their own hard texture, impurities or toxicity. As an important part of solid excipients, mineral excipients that contain some metal elements play indispensable and unique roles in the pretreatment process of traditional Chinese medicine. However, deficiency of holistic understanding of the effect of mineral excipients hinders their application and development. This article reviews several mineral excipients including alumen, talci pulvis, soil, soda lime, halloysitum rubrum and cinnabaris systemically. Their processing significance on traditional Chinese medicines were revealed from components, pharmacodynamics and mechanism aspects. Furthermore, prospect and problems including processing technologies, quality standards of mineral excipients and processing mechanism were put forward. This review supply comprehensive information for better and scientific usage of mineral excipients in processing traditional Chinese medicines.

19.
Front Pharmacol ; 12: 753007, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790125

RESUMO

In recent years, natural polysaccharides have received growing attention and interest in view of their values in food, medical, cosmetics and other fields. Eleutherococcus senticosus (E. senticosus) is a medicine and food homologous plant that possess anti-tumor, anti-inflammatory, central nervous system and cardiovascular protection, anti-radiation, enhancement of human microcirculation, improvement of physical fatigue effects, mainly based on lignans, flavonoids and coumarin types. E. senticosus polysaccharides (ESPS), act as a kind of polysaccharide extracted and isolated from the root and rhizome of E. senticosus, have been found in many applications of medicine and food for their unique biological activity. Nevertheless, the existing studies are mostly concerned with small molecules of E. senticosus, less attention is paid to polysaccharides. Moreover, the types and structural characterization of ESPS reported in existing literature were also not summarized. In this paper, the research progress of ESPS is reviewed from the aspects of extraction, separation, structural characterization and biological activity, future perspectives from points of efficient extraction, resource utilization and quality control standards were also proposed, which provide reference for the further development and utilization of ESPS.

20.
BMC Cancer ; 21(1): 1265, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34814861

RESUMO

BACKGROUND: N6-methyladenine (m6A) is the most common modification of mRNA and IncRNA in higher organisms. m6A has been confirmed to be related to the formation and progression of tumors and m6A-related genes can be used as prognostic biomarkers in a variety of tumors. However, there have been no similar studies on lung squamous cell carcinoma. The main purpose of this study was aimed to explore the differential expression of m6A-related genes in lung squamous cell carcinoma tissues and its relationship with patient clinical prognosis. METHODS: We integrated three m6A writers that catalyze the methylation of adenine on mRNA molecules. The training set including 501 patients with LUSC was collected from The Cancer Genome Atlas (TCGA) database and the test set including 181 patients with LUSC was collected from the Gene Expression Omnibus (GEO) database. Based on the expression level of the m6A methylase gene, we established a tumor subgroup and risk-prognosis model to quantify the risk index and long-term patient prognosis, which were confirmed by principal component analysis (PCA) and receiver operating characteristic (ROC) curve analysis. After lung squamous cell carcinoma tissue specimens were obtained during surgery, immunohistochemistry (IHC) was used to verify the results in vitro. RESULTS: The results of the study showed that the expression of the three m6A methylases in tumor tissues and normal tissues was significantly different (P < 0.05). The survival-prognostic model based on METTL3 gene expression showed better predictive performance (AUC: 0.706). Patients in the high-risk and low-risk groups exhibited significant differences in terms of survival time and 5-year and 10-year survival rates. Immunohistochemistry revealed that patients with high METTL3 expression exhibited a longer survival time than those with low METTL3 expression. CONCLUSIONS: Our study showed that the molecular phenotype based on the expression of METTL3 may be an independent risk factor affecting the prognosis of lung squamous cell carcinoma. These findings not only prove the important role of m6A methylase in lung squamous cell carcinoma, but are also expected to provide more accurate prognostic assessment and individualized treatment for patients with lung squamous cell carcinoma.


Assuntos
Adenosina/análogos & derivados , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , Metiltransferases/genética , Adenina/análogos & derivados , Adenina/metabolismo , Adenosina/genética , Adenosina/metabolismo , Idoso , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Bases de Dados Genéticas , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Metilação , Metiltransferases/metabolismo , Pessoa de Meia-Idade , Análise de Componente Principal , Prognóstico , RNA Mensageiro/metabolismo , Curva ROC , Taxa de Sobrevida , Fatores de Tempo
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