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BACKGROUND: Fanlian Huazhuo Formula (FLHZF) has the functions of invigorating spleen and resolving phlegm, clearing heat and purging turbidity. It has been identified to have therapeutic effects on type 2 diabetes mellitus (T2DM) in clinical application. Non-alcoholic fatty liver disease (NAFLD) is frequently diagnosed in patients with T2DM. However, the therapeutic potential of FLHZF on NAFLD and the underlying mechanisms need further investigation. AIM: To elucidate the effects of FLHZF on NAFLD and explore the underlying hepatoprotective mechanisms in vivo and in vitro. METHODS: HepG2 cells were treated with free fatty acid for 24 hours to induce lipid accumulation cell model. Subsequently, experiments were conducted with the different concentrations of freeze-dried powder of FLHZF for 24 hours. C57BL/6 mice were fed a high-fat diet for 8-week to establish a mouse model of NAFLD, and then treated with the different concentrations of FLHZF for 10 weeks. RESULTS: FLHZF had therapeutic potential against lipid accumulation and abnormal changes in biochemical indicators in vivo and in vitro. Further experiments verified that FLHZF alleviated abnormal lipid metabolism might by reducing oxidative stress, regulating the AMPKα/SREBP-1C signaling pathway, activating autophagy, and inhibiting hepatocyte apoptosis. CONCLUSION: FLHZF alleviates abnormal lipid metabolism in NAFLD models by regulating reactive oxygen species, autophagy, apoptosis, and lipid synthesis signaling pathways, indicating its potential for clinical application in NAFLD.
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Autofagia , Dieta Hiperlipídica , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Metabolismo dos Lipídeos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica , Estresse Oxidativo , Transdução de Sinais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Animais , Autofagia/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Células Hep G2 , Camundongos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Lipogênese/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologiaRESUMO
BACKGROUND: This study aimed to identify metabolic subtypes in ESCA, explore their relationship with immune landscapes, and establish a metabolic index for accurate prognosis assessment. METHODS: Clinical, SNP, and RNA-seq data were collected from 80 ESCA patients from the TCGA database and RNA-seq data from the GSE19417 dataset. Metabolic genes associated with overall survival (OS) and progression-free survival (PFS) were selected, and k-means clustering was performed. Immune-related pathways, immune infiltration, and response to immunotherapy were predicted using bioinformatic algorithms. Weighted gene co-expression network analysis (WGCNA) was conducted to identify metabolic genes associated with co-expression modules. Lastly, cell culture and functional analysis were performed using patient tissue samples and ESCA cell lines to verify the identified genes and their roles. RESULTS: Molecular subtypes were identified based on the expression profiles of metabolic genes, and univariate survival analysis revealed 163 metabolic genes associated with ESCA prognosis. Consensus clustering analysis classified ESCA samples into three distinct subtypes, with MC1 showing the poorest prognosis and MC3 having the best prognosis. The subtypes also exhibited significant differences in immune cell infiltration, with MC3 showing the highest scores. Additionally, the MC3 subtype demonstrated the poorest response to immunotherapy, while the MC1 subtype was the most sensitive. WGCNA analysis identified gene modules associated with the metabolic index, with SLC5A1, NT5DC4, and MTHFD2 emerging as prognostic markers. Gene and protein expression analysis validated the upregulation of MTHFD2 in ESCA. MTHFD2 promotes the progression of ESCA and may be a potential therapeutic target for ESCA. CONCLUSION: The established metabolic index and identified metabolic genes offer potential for prognostic assessment and personalized therapeutic interventions for ESCA, underscoring the importance of targeting metabolism-immune interactions in ESCA. MTHFD2 promotes the progression of ESCA and may be a potential therapeutic target for ESCA.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Prognóstico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Imunoterapia , Regulação para CimaRESUMO
Liver cancer is a common malignancy of the digestive system. Hepatocellular carcinoma (HCC) accounts for the most majority of these tumors and it has brought a heavy medical burden to underdeveloped countries and regions. Many factors affect the prognosis of HCC patients, however, there is no specific statistical model to predict the survival time of clinical patients. This study derived a risk factor signature of HCC and reliable clinical prediction model by statistically analyzing The Surveillance, Epidemiology, and End Results (SEER) database patient information using an open source package in the python environment.
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OBJECTIVE: This cross-sectional study aimed to investigate the current attention and intervention of oncologists on oxaliplatin (OXA)-induced adverse reactions (ADRs). METHODS: In 31 provinces or administrative regions across China, 401 oncologists were surveyed through a self-designed questionnaire. The survey queried the basic information of respondents, clinical use of OXA, OXA-induced ADRs, and relative interventions. Chi-square tests and multiple logistic regression were used to explore the sociodemographic factors influencing the safety perception of OXA and the relevant interventions. RESULTS: The survey showed that the age of respondents was mainly distributed between 30 and 40 years and the working period for most oncologists was no more than 5 years. Oncologists with long working years were more willing to conduct patient education and inquire about ADRs than those with short working years. The rate of ADRs reported by oncologists with intermediate professional titles was significantly higher than that reported by oncologists with junior and senior professional titles. CONCLUSION: Our findings indicate that oncologists in mainland China are concerned about OXA-induced ADRs, but the reporting of ADRs still needs to be strengthened. Therefore, training and educational programs are urgently needed to improve the risk management of OXA-induced ADRs among oncologists.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Oncologistas , Humanos , Adulto , Estudos Transversais , Oxaliplatina/efeitos adversos , Sistemas de Notificação de Reações Adversas a Medicamentos , China/epidemiologiaRESUMO
In this study, we investigated the metabonomic profiles of Apostichopus japonicus using an LC-MS-based method in conjunction with multivariate data analysis. Based on the PLS-DA model, 85 differential metabolites (VIP value >1.0) were obtained from viscera and body wall samples. The MS/MS and NMR experiments were used for the qualitative identification of the characteristic peaks. Sphingoid-based nucleoside analogues were the main components in Chinese A. japonicus viscera. Our findings demonstrate that A. japonicus viscera contain a large number of compounds that may have applications as nutraceuticals or pharmaceuticals.
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Biomarcadores/análise , Metabolômica/métodos , Nucleosídeos/análise , Stichopus/genética , Vísceras/metabolismo , Animais , Biomarcadores/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Espectroscopia de Ressonância Magnética/métodos , Análise Multivariada , Nucleosídeos/isolamento & purificação , Nucleosídeos/metabolismo , Análise de Componente Principal/métodos , Espectrometria de Massas em Tandem/métodosRESUMO
Marsdenia tenacissima exhibits biological activity with heat-clearing and detoxifying properties, relieving coughs and asthma and exerting anticancer and anti-HIV effects. Tenacissioside H (TH) is a Chinese medicine monomer extracted from the dried stem of Marsdenia tenacissima. We investigated the in vivo anti-inflammatory activity of TH using three different zebrafish inflammation models: local inflammation induced by tail cutting, acute inflammation induced by CuSO4, and systemic inflammation induced by lipopolysaccharide (LPS). Real time-polymerase chain reaction (RT-PCR) was used to elucidate the mechanism of TH action against LPS-induced inflammatory responses. Our results showed TH significantly reduced the number of macrophages in the injured zebrafish tail, inhibited CuSO4-induced migration of macrophages toward the neural mound, and decreased the distribution of macrophages in tail fin compared to LPS-treated group. Furthermore, TH inhibits LPS-induced inflammation responses in zebrafish by modulating the nuclear factor κB (nf-κb) and p38 pathways to regulate inflammatory cytokines, such as tumor necrosis factor-α (tnf-α), cyclooxygenase (cox-2), interleukin-1b (il-1b), interleukin-8 (il-8), interleukin-10 (il-10), nitric oxide synthase (nos2b) and prostaglandin E synthase (ptges). In conclusion, TH possesses anti-inflammation activity via the regulation of the nf-κb and p38 pathways. This finding provides a reference for the clinical application of Xiaoaiping (the trade name of Marsdenia tenacissima extract).
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Anti-Inflamatórios/farmacologia , NF-kappa B/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Sulfato de Cobre/toxicidade , Embrião não Mamífero , Lipopolissacarídeos/farmacologia , NF-kappa B/genética , Transdução de Sinais/efeitos dos fármacos , Peixe-Zebra , Proteínas de Peixe-Zebra/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genéticaRESUMO
A new coumarin, 7-hydroxy-4,6-dimethoxy-5-methylcoumarin (1), was isolated from the aerial parts of Clematis delavayi var. spinescens together with 17 known compounds. Their structures were identified by extensive spectral analysis, especially 2D NMR techniques. Antiangiogenic effects of all compounds were evaluated using a zebrafish model.
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Clematis/química , Cumarínicos/química , Cumarínicos/farmacologia , Inibidores da Angiogênese/farmacologia , Animais , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Ftalazinas/farmacologia , Piridinas/farmacologia , Peixe-ZebraRESUMO
Ten new ingol lathyrane-type diterpenes (1-10) and two known ingenol derivatives (11 and 12) were isolated from the aerial parts of Euphorbia royleana. The structures of 1-10 were elucidated on the basis of spectroscopic methods including 2D NMR analysis, and the structure of compound 1 was confirmed by single-crystal X-ray crystallography. Antiangiogenic effects of all compounds except for 5 were tested using a zebrafish model, with compounds 11 and 12 being active in this bioassay.
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Inibidores da Angiogênese/isolamento & purificação , Inibidores da Angiogênese/farmacologia , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Euphorbia/química , Inibidores da Angiogênese/química , Animais , Cristalografia por Raios X , Modelos Animais de Doenças , Diterpenos/química , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Peixe-ZebraRESUMO
Infrared vibration spectra of nanosize (SiO2)n,O2H4 with line, ring and cage structures were calculated using the density-functional theory (B3LYP) at 6-31G(d) level. For quasi 1D (one dimension) line and ring structure, the frequencies of stronger infrared vibration modes monotonically change as a function of the length, which shows strong size effect. The IR vibration modes in directions parallel and perpendicular to the axis of nanoline or nanoring have opposite size dependence trends, showing the real vibration anisotropy property of nano scale material. Due to constructional complexity, cage structure does not have quasi 1D character. Morever, IR vibration modes increase as structural symmetry decreases. Vibrations of two-membered ring, isolated hydroxyls of three structures and framework SiO4 tetrahedron in cage structure agree well with experimental data. Theoretical calculation result of IR spectra can be used to guide characterization of silicon oxide nano scale materials fabricated in experiment.