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BACKGROUND: Standardized patients (SPs) simulation training models have been widely used in various fields, the study of using SPs in Traditional Chinese medicine (TCM) is still a new filed. Previous studies have demonstrated the effectiveness of occupational SP for TCM (OSP-TCM), which has an increasingly problem of high time and financial costs. The faculty SPs for TCM (FSP-TCM) simulation training model may provide a better alternative. This study aims to test and determine whether FSP-TCM simulations are more cost-effective than OSP-TCM and traditional educational models to improve the clinical competence of TCM students. METHODS: This study was a single-blind, prospective, randomized controlled trial conducted between February 2023 and October 2023. The participants were randomized into FSP-TCM group, OSP-TCM group and traditionally taught group (TT group) in the ratio of 1:1:1. The duration of this training program was 12 weeks (36 credit hours). Formative and summative assessments were integrated to evaluate the effectiveness of teaching and learning. Three distinct questionnaires were utilized to collect feedback from students, SPs, and teachers at the conclusion of the course. Additionally, analysis of cost comparisons between OSP-TCM and FSP-TCM were performed in the study. RESULTS: The study comprised a total of 90 students, with no dropouts during the research. In the formative evaluation, students assigned to both the FSP-TCM and OSP-TCM groups demonstrated higher overall scores compared to those in the TT group. Notably, their performance in "physical examination" (Pa = 0.01, Pb = 0.04, Pc = 0.93) and "comprehensive ability" (Pa = 0.01, Pb = 0.006, Pc = 0.96) significantly exceeded that of the TT group. In the summary evaluation, both SP-TCM groups students outperforms TT group in the online systematic knowledge test (Pa = 0.019, Pb = 0.04, Pc = 0.97), the application of TCM technology (Pa = 0.01, Pb = 0.03, Pc = 0.93) and real-time assessment (Pa= 0.003, Pb = 0.01, Pc = 0.93). The feedback questionnaire demonstrated that both SP-TCM groups showed higher levels of agreement for this course in "satisfaction with the course" (Pa = 0.03; Pb = 0.02) and "enhanced TCM clinical skills" (Pa = 0.02; Pb = 0.03) than TT group. The SP questionnaire showed that more FSPs than OSPs in "provided professional feedback" (FSPs: strongly agree 30%, agree 50% vs. OSPs: strongly agree 20%, agree 40%. P = 0.69), and in "gave hints" during the course (FSPs: strongly agree 10%, agree 30% vs. OSPs: strongly agree 0%, agree 10%. P = 0.42). It is noteworthy that FSP-TCM was significantly lower than the OSP-TCM in overall expense (FSP-TCM $7590.00 vs. OSP-TCM $17415.60), and teachers have a positive attitude towards the FSP-TCM. CONCLUSION: FSP-TCM training mode showed greater effectiveness than traditional teaching method in improving clinical competence among TCM students. It was feasible, practical, and cost-effective, and may serve as an alternative method to OSP-TCM simulation.
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Competencia Clínica , Medicina Tradicional China , Humanos , Estudios Prospectivos , Masculino , Femenino , Método Simple Ciego , Simulación de Paciente , Estudiantes de Medicina , Entrenamiento Simulado , Adulto Joven , Evaluación Educacional , Educación de Pregrado en Medicina/métodos , Enseñanza , Análisis Costo-Beneficio , AdultoRESUMEN
Exosome-derived microRNAs (miRNAs) are biomacromolecules and nanoscale extracellular vesicles originating from intracellular compartments that are secreted by most cells into the extracellular space. This review examines the formation and function of exosomal miRNAs in biological information transfer, explores the pathogenesis of vitiligo, and highlights the relationship between exosomal miRNAs and vitiligo. The aim is to deepen the understanding of how exosomal miRNAs influence immune imbalance, oxidative stress damage, melanocyte-keratinocyte interactions, and melanogenesis disorders in the development of vitiligo. This enhanced understanding may contribute to the development of potential diagnostic and therapeutic options for vitiligo.
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Exosomas , Melanocitos , MicroARNs , Vitíligo , Vitíligo/genética , Vitíligo/metabolismo , Humanos , Exosomas/metabolismo , Exosomas/genética , MicroARNs/genética , Melanocitos/metabolismo , Animales , Estrés Oxidativo , Queratinocitos/metabolismoRESUMEN
Gastric cancer (GC) is a prevalent gastrointestinal tumor characterized by high mortality and recurrence rates. Current treatments often have limitations, prompting researchers to explore novel anti-tumor substances and develop new drugs. Flavonoids, natural compounds with diverse biological activities, are gaining increasing attention in this regard. We searched from PubMed, Web of Science, SpringerLink and other databases to find the relevant literature in the last two decades. Using "gastric cancer", "stomach cancers", "flavonoid", "bioflavonoid", "2-Phenyl-Chromene" as keywords, were searched, then analyzed and summarized the mechanism of flavonoids in the treatment of GC. It was revealed that the anti-tumor mechanism of flavonoids involves inhibiting tumor growth, proliferation, invasion, and metastasis, as well as inducing cell death through various processes such as apoptosis, autophagy, ferroptosis, and pyroptosis. Additionally, combining flavonoids with other chemotherapeutic agents like 5-FU and platinum compounds can potentially reduce chemoresistance. Flavonoids have also demonstrated enhanced biological activity when used in combination with other natural products. Consequently, this review proposes innovative perspectives for the development of flavonoids as new anti-GC agents.
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Flavonoides , Transducción de Señal , Neoplasias Gástricas , Humanos , Flavonoides/farmacología , Flavonoides/química , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Transducción de Señal/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Apoptosis/efectos de los fármacos , AnimalesRESUMEN
BACKGROUND: Myelosuppression is a serious and common complication of radiotherapy and chemotherapy in cancer patients and is characterized by a reduction of peripheral blood cells. This condition not only compromises the efficacy of treatment but also increases the risk of patient death. Natural products are emerging as promising adjuvant therapies due to their antioxidant properties, ability to modulate immune responses, and capacity to stimulate haematopoietic stem cell proliferation. These therapies demonstrate significant potential in ameliorating myelosuppression. METHODS: A systematic review of the literature was performed utilizing the search terms "natural products," "traditional Chinese medicine," and "myelosuppression" across prominent databases, including Google Scholar, PubMed, and Web of Science. All pertinent literature was meticulously analysed and summarized. The objective of this study was to perform a pertinent analysis to elucidate the mechanisms underlying myelosuppression and to categorize and synthesize information on natural products and traditional Chinese medicines employed for the therapeutic management of myelosuppression. RESULTS: Myelosuppression resulting from drug and radiation exposure, viral infections, and exosomes is characterized by multiple underlying mechanisms involving immune factors, target genes, and the activation of diverse signalling pathways, including the (TGF-ß)/Smad pathway. Recently, traditional Chinese medicine monomers and compounds, including more than twenty natural products, such as Astragalus and Angelica, have shown promising potential as therapeutics for ameliorating myelosuppression. These natural products exert their effects by modulating haematopoietic stem cells, immune factors, and critical signalling pathways. CONCLUSIONS: Understanding the various mechanisms of myelosuppression facilitates the exploration of natural product therapies and biological target identification for evaluating herbal medicine efficacy. This study aimed to establish a foundation for the clinical application of natural products and provide methodologies and technical support for exploring additional treatments for myelosuppression.
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Productos Biológicos , Medicina Tradicional China , Humanos , Productos Biológicos/farmacología , Medicamentos Herbarios Chinos/farmacología , Neoplasias/tratamiento farmacológico , Animales , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Hepatocellular carcinoma (HCC) has a high morbidity and mortality rate, and the survival rate of HCC patients remains low. Animal medicines have been used as potential therapeutic tools throughout the long history due to their different structures of biologically active substances with high affinity to the human body. Here, we focus on the effects and the mechanism of action of animal-derived natural products against HCC, which were searched in databases encompassing Web of Science, PubMed, Embase, Science Direct, Springer Link, and EBSCO. A total of 24 natural products from 12 animals were summarized. Our study found that these natural products have potent anti-hepatocellular carcinoma effects. The mechanism of action involving apoptosis induction, autophagy induction, anti-proliferation, anti-migration, and anti-drug resistance via phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), Ras/extracellular signal regulated kinases (ERK)/mitogen-activated protein kinase (MAPK), Wnt/ß-catenin, and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways. Huachansu injection and sodium cantharidate have been used in clinical applications with good efficacy. We review the potential of animal-derived natural products and their derivatives in the treatment of HCC to date and summarize their application prospect and toxic side effects, hoping to provide a reference for drug development for HCC.
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BACKGROUND: Cholestatic hepatitis is recognized as a significant contributor to the development of liver fibrosis and cirrhosis. As a well-known classic formula for the treatment of cholestatic hepatitis, Yinchenhao decoction (YCHD) is widely used in countries in Asia, including China, Japan, and Korea. However, in recent years, a risk of liver injury has been reported from Rheum palmatum L. and Gardenia jasmonoides J.Ellis which are the main ingredients of YCHD. Therefore, the question arises whether YCHD is still safe enough for the treatment of cholestatic hepatitis or whether an optimized ratio of ingredients should be applied. These is inevitable questions for the clinical application of YCHD. PURPOSE: To provide a scientific basis for the clinical application of YCHD through a combination of meta-analysis and network pharmacology and to find the best ratio of components to ensure optimal therapeutic efficacy and safety. At the same time, a deeper understanding of the mechanisms of YCHD was explored. METHODS: We retrieved relevant trials from various databases including PubMed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP and Wanfang databases up to August 2023. After screening for inclusion and exclusion criteria, we assessed efficiency, ALT, AST, and TBIL as outcome parameters. The relevant data underwent a network meta-analysis using STATA 16.0 software. Based on network pharmacology, we screened the disease targets, active ingredients, and targets related to YCHD. The targets were visualized using Cytoscape 3.9.1. Then, potential mechanisms were explored based on bioinformatic techniques. RESULTS: Twenty eligible studies were finally screened and a total of 1,591 patients who fulfilled the inclusion criteria were enrolled in the study. The meta-analysis results indicated that TG-c (treatment group c) [(Artemisia capillaris Thunb. : Gardenia jasminoides J.Ellis : Rheum palmatum L. = 10:5:2-10:5:3) + CT] was the most promising therapeutic approach, demonstrating superior efficacy and notable improvements in both AST and TBIL levels. For ALT, TG-d [(Artemisia capillaris : Gardenia jasminoides : Rheum palmatum = 5:1:1-5:2:1) + CT] exhibited the greatest potential as optimal therapy option. Based on the surface under the cumulative ranking curve (SUCRA) values, TG-c was the best therapy in terms of efficiency and improvement in TBIL levels, while TG-d was the most effective in reducing ALT levels. For AST levels, TG-e [(Artemisia capillaris : Gardenia jasminoides : Rheum palmatum = 5:2:2-5:3:3) + CT] was the most effective therapy. The comprehensive analysis revealed that TG-c exhibited the most pronounced efficacy. Combined network pharmacology, GO enrichment analysis and KEGG pathway enrichment analysis displayed that the key target genes of Artemisia capillaris, Rheum palmatum, and Gardenia jasminoides were closely involved in inflammation response, bile transport, apoptosis, oxidative stress, and regulation of leukocyte migration. Notably, bile secretion dominated the common pathway of the three herbs. On the other hand, Artemisia capillaris exhibited a unique mode of action by regulating the IL-17 signaling pathway, which may play a crucial role in its effectiveness. CONCLUSION: Based on our findings, the optimal TG-C demonstrated the most favorable overall therapeutic efficacy by increasing the dosage of Artemisia capillaris while reducing the dosage of Gardenia jasminoides and Rheum palmatum. This is attributed to the potent ability of Artemisia capillaris. to effectively modulate the IL-17 signaling pathway, thereby exerting a beneficial therapeutic effect. Conversely, Gardenia jasminoides and Rheum palmatum may potentially enhance the activation of the NF-кB signaling pathway, thereby elevating the risk of hepatotoxicity.
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Medicamentos Herbarios Chinos , Farmacología en Red , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Metaanálisis en Red , Colestasis/tratamiento farmacológico , Rheum/química , Hepatitis/tratamiento farmacológicoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia lactiflora Pall. (PLP), a traditional Chinese medicine, is recognized for its antioxidative and anti-apoptotic properties. Despite its potential medicinal value, the mechanisms underlying its efficacy have been less explored, particularly in alleviating acute liver injury (ALI) caused by excessive intake of acetaminophen (APAP). AIM OF THE STUDY: This study aims to elucidate the role and mechanisms of PLP in mitigating oxidative stress and apoptosis induced by APAP. MATERIALS AND METHODS: C57BL/6 male mice were pre-treated with PLP for seven consecutive days, followed by the induction of ALI using APAP. Liver pathology was assessed using HE staining. Serum indicators, immunofluorescence (IF), immunohistochemical (IHC), and transmission electron microscopy were employed to evaluate levels of oxidative stress, ferroptosis and apoptosis. Differential expression proteins (DEPs) in the APAP-treated and PLP pre-treated groups were analyzed using quantitative proteomics. Subsequently, the potential mechanisms of PLP pre-treatment in treating ALI were validated using western blotting, molecular docking, molecular dynamics simulations, and surface plasmon resonance (SPR) analysis. RESULTS: The UHPLC assay confirmed the presence of three compounds, i.e., albiflorin, paeoniflorin, and oxypaeoniflorin. Pre-treatment with PLP was observed to ameliorate liver tissue pathological damage through HE staining. Further confirmation of efficacy of PLP in alleviating APAP-induced liver injury and oxidative stress was established through liver function serum biochemical indicators, IF of reactive oxygen species (ROS) and IHC of glutathione peroxidase 4 (GPX4) detection. However, PLP did not demonstrate a significant effect in alleviating APAP-induced ferroptosis. Additionally, transmission electron microscopy and TUNEL staining indicated that PLP can mitigate hepatocyte apoptosis. PKC-ERK pathway was identified by proteomics, and subsequent molecular docking, molecular dynamics simulations, and SPR verified binding of the major components of PLP to ERK protein. Western blotting demonstrated that PLP suppressed protein kinase C (PKC) phosphorylation, blocking extracellular signal-regulated kinase (ERK) phosphorylation and inhibiting oxidative stress and cell apoptosis. CONCLUSION: This study demonstrates that PLP possesses hepatoprotective abilities against APAP-induced ALI, primarily by inhibiting the PKC-ERK cascade to suppress oxidative stress and cell apoptosis.
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Acetaminofén , Apoptosis , Enfermedad Hepática Inducida por Sustancias y Drogas , Ratones Endogámicos C57BL , Estrés Oxidativo , Paeonia , Animales , Acetaminofén/toxicidad , Paeonia/química , Estrés Oxidativo/efectos de los fármacos , Masculino , Apoptosis/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Ratones , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/química , Simulación del Acoplamiento Molecular , Antioxidantes/farmacologíaRESUMEN
Background: Clinicians and healthcare policymakers have been drenched with a deluge of overlapping meta-analyses (MAs), and the necessity for comprehensive and clearly defined evidence of Janus kinase inhibitors (JKIs) in atopic dermatitis (AD) is urgent. Methods: Six databases were searched for MAs published until October 2023. Qualitative description of MAs was mainly used, and Investigator's Global Assessment response (IGA response), the 75% improvement in Eczema Area and Severity Index (the EASI75), peak pruritus Numerical rating score (PP-NRS), and adverse effects were cited to describe the efficacy and safety of JKIs. The methodological quality of the included MAs was assessed by A Measurement Tool to Assess Systematic Reviews II (AMSTAR II), and the quality of evidence was evaluated by the grading of recommendations, assessment, development, and evaluation (GRADE). Results: Sixteen MAs were pooled in this review, of which five studies appraised JKIs, five appraised systemic JKIs, five papers assessed abrocitinib only, and one assessed baricitinib. Two studies were of "high" methodological quality and 14 MAs were of "moderate" quality. Eleven MAs integrated the results of JKIs and reported that JKIs provide faster onset of IGA response (RR=2.83, 95% CI [2.25, 3.56], high-quality evidence). Similarly, 10 MAs showed that JAK inhibitors were more effective in improving the EASI75 (RR=2.84, 95% CI [2.2, 3.67], high-quality evidence). Results from 12 MAs showed JKIs were active in reducing the PP-NRS (SMD=-0.49, 95% CI [-0.67, -0.32]). All MAs affirmed JKIs added no adverse effects leading to discontinuation and serious adverse events (P<0.05). However, 200mg of abrocitinib had a higher risk of acne (RR=4.34, 95% CI [1.61, 11.71), herpes zoster (RR=1.64, 95% CI [0.42, 6.39]), headache (RR=1.76, 95% CI [1.03, 3]), and nausea (RR=7.81, 95% CI [3.84, 15.87]). Upadacitinib was known to increase acne (RR=6.23, 95% CI [4.08, 9.49]), nasopharyngitis (RR=1.36, 95% CI [1.03, 1.8]) and blood creatine phosphokinase (blood CPK) (RR=2.41, 95% CI [1.47, 3.95]). Baricitinib at 2mg was associated with increased blood CPK (RR=2.25, 95% CI [1.1, 2.97]). Conclusion: Compared to placebo or dupilumab, the administration of JKIs can ameliorate IGA response more effectively, improve the EASI75, and relieve pruritus without severe adverse effect, while accompanied by more acne, nasopharyngitis, headache, and digestive disturbances. The curative effect of 200 mg of abrocitinib is significant and more caution should be given in patients with gastrointestinal dysfunction, herpes zoster, and those who are acne-prone. Baricitinib and upadacitinib should be avoided in populations at high risk for cardiovascular events. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369369, PROSPERO (CRD42022369369).
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Acné Vulgar , Azetidinas , Dermatitis Atópica , Herpes Zóster , Inhibidores de las Cinasas Janus , Nasofaringitis , Purinas , Pirazoles , Pirimidinas , Sulfonamidas , Humanos , Dermatitis Atópica/tratamiento farmacológico , Inhibidores de las Cinasas Janus/efectos adversos , Prurito/tratamiento farmacológico , Cefalea , Inmunoglobulina A/uso terapéuticoRESUMEN
BACKGROUND: Epigallocatechin-3-gallate (EGCG), the primary active compound in green tea, is recognized for its significant anti-inflammatory properties and potential pharmacological effects on inflammatory bowel disease (IBD). However, comprehensive preclinical evidence supporting the use of EGCG in treating IBD is currently insufficient. PURPOSE: To evaluate the efficacy of EGCG in animal models of IBD and explore potential underlying mechanisms, serving as a groundwork for future clinical investigations. METHODS: A systematic review of pertinent preclinical studies published until September 1, 2023, in databases such as PubMed, Embase, Web of Science, and Cochrane Library was conducted, adhering to stringent quality criteria. The potential mechanisms via which EGCG may address IBD were summarized. STATA v16.0 was used to perform a meta-analysis to assess IBD pathology, inflammation, and indicators of oxidative stress. Additionally, dose-response analysis and machine learning models were utilized to evaluate the dose-effect relationship and determine the optimal dosage of EGCG for IBD treatment. RESULTS: The analysis included 19 studies involving 309 animals. The findings suggest that EGCG can ameliorate IBD-related pathology in animals, with a reduction in inflammatory and oxidative stress indicators. These effects were observed through significant changes in histological scores, Disease Activity Index, Colitis Macroscopic Damage Index and colon length; a decrease in markers such as interleukin (IL)-1ß, IL-6 and interferon-γ; and alterations in malondialdehyde, superoxide dismutase, glutathione, and catalase levels. Subgroup analysis indicated that the oral administration route of EGCG exhibited superior efficacy over other administration routes. Dose-response analysis and machine learning outcomes highlighted an optimal EGCG dosage range of 32-62 mg/kg/day, with an intervention duration of 4.8-13.6 days. CONCLUSIONS: EGCG exhibits positive effects on IBD, particularly when administered at the dose range of 32 - 62 mg/kg/day, primarily attributed to its ability to regulate inflammation and oxidative stress levels.
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Antiinflamatorios , Catequina , Catequina/análogos & derivados , Enfermedades Inflamatorias del Intestino , Estrés Oxidativo , Catequina/farmacología , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Animales , Estrés Oxidativo/efectos de los fármacos , Antiinflamatorios/farmacología , Modelos Animales de Enfermedad , Té/química , Relación Dosis-Respuesta a DrogaRESUMEN
Neutrophil extracellular traps (NETs) have emerged as a critical factor in malignant hematologic disease pathogenesis. These structures, comprising DNA, histones, and cytoplasmic proteins, were initially recognized for their role in immune defense against microbial threats. Growing evidence suggests that NETs contribute to malignant cell progression and dissemination, representing a double-edged sword. However, there is a paucity of reports on its involvement in hematological disorders. A comprehensive understanding of the intricate relationship between malignant cells and NETs is necessary to explore effective therapeutic strategies. This review highlights NET formation and mechanisms underlying disease pathogenesis. Moreover, we discuss recent advancements in targeted inhibitor development for selective NET disruption, empowering precise design and efficacious therapeutic interventions for malignant hematologic diseases.
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Trampas Extracelulares , Enfermedades Hematológicas , Neoplasias Hematológicas , Neoplasias , Humanos , Neutrófilos/metabolismo , Histonas/metabolismo , ADN/metabolismo , Neoplasias Hematológicas/metabolismo , Neoplasias/patología , Enfermedades Hematológicas/metabolismoRESUMEN
The SARS-CoV-2 virus, belonging to the Coronavirus genus, which poses a threat to human health worldwide. Current therapies focus on inhibiting viral replication or using anti-inflammatory/immunomodulatory compounds to enhance host immunity. This makes the active ingredients of traditional Chinese medicine compounds ideal therapies due to their proven safety and minimal toxicity. Previous research suggests that andrographolide and baicalin inhibit coronaviruses; however, their synergistic effects remain unclear. Here, we studied the antiviral mechanisms of their synergistic use in vitro and in vivo. We selected the SARS-CoV-2 pseudovirus for viral studies and found that synergistic andrographolide and baicalein significantly reduced angiotensin-converting enzyme 2 protein level and viral entry of SARS-CoV-2 into cells compared to singal compound individually and inhibited the major protease activity of SARS-CoV-2. This mechanism is essential to reduce the pathogenesis of SARS-CoV-2. In addition, their synergistic use in vivo also inhibited the elevation of pro-inflammatory cytokines, including IL-6 and TNF-α-the primary cytokines in the development of acute respiratory distress syndrome (the main cause of COVID-19 deaths). In conclusion, this study shows that synergistic andrographolide and baicalein treatment acts as potent inhibitors of coronavirus mechanisms in vitro and in vivo-and is more effective together than in isolation.
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Enzima Convertidora de Angiotensina 2 , Diterpenos , Flavonoides , SARS-CoV-2 , Humanos , Enzima Convertidora de Angiotensina 2/metabolismo , Regulación hacia Abajo , SARS-CoV-2/fisiología , Citocinas/metabolismo , Antivirales/farmacología , Antivirales/metabolismoRESUMEN
Previous studies have revealed an association between dietary factors and atopic dermatitis (AD). To explore whether there was a causal relationship between diet and AD, we performed Mendelian randomisation (MR) analysis. The dataset of twenty-one dietary factors was obtained from UK Biobank. The dataset for AD was obtained from the publicly available FinnGen consortium. The main research method was the inverse-variance weighting method, which was supplemented by MRâEgger, weighted median and weighted mode. In addition, sensitivity analysis was performed to ensure the accuracy of the results. The study revealed that beef intake (OR = 0·351; 95 % CI 0·145, 0·847; P = 0·020) and white bread intake (OR = 0·141; 95 % CI 0·030, 0·656; P = 0·012) may be protective factors against AD. There were no causal relationships between AD and any other dietary intake factors. Sensitivity analysis showed that our results were reliable, and no heterogeneity or pleiotropy was found. Therefore, we believe that beef intake may be associated with a reduced risk of AD. Although white bread was significant in the IVW analysis, there was large uncertainty in the results given the wide 95 % CI. Other factors were not associated with AD in this study.
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Dermatitis Atópica , Dieta , Análisis de la Aleatorización Mendeliana , Dermatitis Atópica/genética , Dermatitis Atópica/etiología , Humanos , Factores de Riesgo , Pan , Carne Roja/efectos adversos , Bovinos , Reino Unido/epidemiología , AnimalesRESUMEN
Background: Matrine, an alkaloid derived from the dried roots of Sophora flavescens Aiton, has been utilized for the treatment of liver diseases, but its potential hepatotoxicity raises concerns. However, the precise condition and mechanism of action of matrine on the liver remain inconclusive. Therefore, the objective of this systematic review and meta-analysis is to comprehensively evaluate both the hepatoprotective and hepatotoxic effects of matrine and provide therapeutic guidance based on the findings. Methods: The meta-analysis systematically searched relevant preclinical literature up to May 2023 from eight databases, including PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, WanFang Med Online, China Science and Technology Journal Database, and China Biomedical Literature Service System. The CAMARADES system assessed the quality and bias of the evidence. Statistical analysis was conducted using STATA, which included the use of 3D maps and radar charts to display the effects of matrine dosage and frequency on hepatoprotection and hepatotoxicity. Results: After a thorough screening, 24 studies involving 657 rodents were selected for inclusion. The results demonstrate that matrine has bidirectional effects on ALT and AST levels, and it also regulates SOD, MDA, serum TG, serum TC, IL-6, TNF-α, and CAT levels. Based on our comprehensive three-dimensional analysis, the optimal bidirectional effective dosage of matrine ranges from 10 to 69.1 mg/kg. However, at a dose of 20-30 mg/kg/d for 0.02-0.86 weeks, it demonstrated high liver protection and low toxicity. The molecular docking analysis revealed the interaction between MT and SERCA as well as SREBP-SCAP complexes. Matrine could alter Ca2+ homeostasis in liver injury via multiple pathways, including the SREBP1c/SCAP, Notch/RBP-J/HES1, IκK/NF-κB, and Cul3/Rbx1/Keap1/Nrf2. Conclusion: Matrine has bidirectional effects on the liver at doses ranging from 10 to 69.1 mg/kg by influencing Ca2+ homeostasis in the cytoplasm, endoplasmic reticulum, Golgi apparatus, and mitochondria. Systematic review registration: https://inplasy.com/, identifier INPLASY202340114.
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Background: Pathological progression from non-alcoholic fatty liver disease (NAFLD) to liver fibrosis (LF) to hepatocellular carcinoma (HCC) is a common dynamic state in many patients. Curcumin, a dietary supplement derived from the turmeric family, is expected to specifically inhibit the development of this progression. However, there is a lack of convincing evidence. Methods: The studies published until June 2023 were searched in PubMed, Web of Science, Embase, and the Cochrane Library databases. The SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) approach was used to evaluate the certainty of evidence. StataSE (version 15.1) and Origin 2021 software programs were used to analyze the critical indicators. Results: Fifty-two studies involving 792 animals were included, and three disease models were reported. Curcumin demonstrates a significant improvement in key indicators across the stages of NAFLD, liver fibrosis, and HCC. We conducted a detailed analysis of common inflammatory markers IL-1ß, IL-6, and TNF-α, which traverse the entire disease process. The research results reveal that curcumin effectively hinders disease progression at each stage by suppressing inflammation. Curcumin exerted hepatoprotective effects in the dose range from 100 to 400 mg/kg and treatment duration from 4 to 10 weeks. The mechanistic analysis reveals that curcumin primarily exerts its hepatoprotective effects by modulating multiple signaling pathways, including TLR4/NF-κB, Keap1/Nrf2, Bax/Bcl-2/Caspase 3, and TGF-ß/Smad3. Conclusion: In summary, curcumin has shown promising therapeutic effects during the overall progression of NAFLD-LF-HCC. It inhibited the pathological progression by synergistic mechanisms related to multiple pathways, including anti-inflammatory, antioxidant, and apoptosis regulation.
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Hepatocellular carcinoma (HCC), presently the second leading cause of global cancer-related mortality, continues to pose significant challenges in the realm of medical oncology, impacting both clinical drug selection and mechanistic research. Recent investigations have unveiled autophagy-related signaling as a promising avenue for HCC treatment. A growing body of research has highlighted the pivotal role of autophagy-modulating natural products in inhibiting HCC progression. In this context, we provide a concise overview of the fundamental autophagy mechanism and delineate the involvement of autophagic signaling pathways in HCC development. Additionally, we review pertinent studies demonstrating how natural products regulate autophagy to mitigate HCC. Our findings indicate that natural products exhibit cytotoxic effects through the induction of excessive autophagy, simultaneously impeding HCC cell proliferation by autophagy inhibition, thereby depriving HCC cells of essential energy. These effects have been associated with various signaling pathways, including PI3K/AKT, MAPK, AMPK, Wnt/ß-catenin, Beclin-1, and ferroautophagy. These results underscore the considerable therapeutic potential of natural products in HCC treatment. However, it is important to note that the present study did not establish definitive thresholds for autophagy induction or inhibition by natural products. Further research in this domain is imperative to gain comprehensive insights into the dual role of autophagy, equipping us with a better understanding of this double-edged sword in HCC management.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Macroautofagia , Fosfatidilinositol 3-Quinasas/metabolismo , Línea Celular Tumoral , Autofagia , Proliferación CelularRESUMEN
BACKGROUND: (-)-Asarinin (Asarinin) is the primary component in the extract of the herb Asarum sieboldii Miq. It possesses various functions, including pain relief, anti-viral and anti-tuberculous bacilli effects, and inhibition of tumor growth. Gastric precancerous lesion (GPL) is a common but potentially carcinogenic chronic gastrointestinal disease, and its progression can lead to gastric dysfunction and cancer development. However, the protective effects of asarinin against GPL and the underlying mechanisms remain unexplored. METHODS: A premalignant cell model (methylnitronitrosoguanidine-induced malignant transformation of human gastric epithelial cell strain, MC cells) and a GPL animal model were established and then were treated with asarinin. The cytotoxic effect of asarinin was assessed using a CCK8 assay. Detection of intracellular reactive oxygen species (ROS) using DCFH-DA. Apoptosis in MC cells was evaluated using an annexin V-FITC/PI assay. We performed western blot analysis and immunohistochemistry (IHC) to analyze relevant markers, investigating the in vitro and in vivo therapeutic effects of asarinin on GPL and its intrinsic mechanisms. RESULTS: Our findings showed that asarinin inhibited MC cell proliferation, enhanced intracellular ROS levels, and induced cell apoptosis. Further investigations revealed that the pharmacological effects of asarinin on MC cells were blocked by the ROS scavenger N-acetylcysteine. IHC revealed a significant upregulation of phospho-signal transducer and activator of transcription 3 (p-STAT3) protein expression in human GPL tissues. In vitro, asarinin exerted its pro-apoptotic effects in MC cells by modulating the STAT3 signaling pathway. Agonists of STAT3 were able to abolish the effects of asarinin on MC cells. In vivo, asarinin induced ROS accumulation and inhibited the STAT3 pathway in gastric mucosa of mice, thereby halting and even reversing the development of GPL. CONCLUSION: Asarinin induces apoptosis and delays the progression of GPL by promoting mitochondrial ROS production, decreasing mitochondrial membrane potential (MMP), and inhibiting the STAT3 pathway.
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Dioxoles , Lignanos , Lesiones Precancerosas , Humanos , Ratones , Animales , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Lignanos/farmacología , Proliferación Celular , Lesiones Precancerosas/inducido químicamente , Lesiones Precancerosas/tratamiento farmacológico , Lesiones Precancerosas/patología , Apoptosis , Factor de Transcripción STAT3/metabolismo , Línea Celular TumoralRESUMEN
As the body's largest organ, the skin harbors a highly diverse microbiota, playing a crucial role in resisting foreign pathogens, nurturing the immune system, and metabolizing natural products. The dysregulation of human skin microbiota is implicated in immune dysregulation and inflammatory responses. This review delineates the microbial alterations and immune dysregulation features in common Inflammatory Skin Diseases (ISDs) such as psoriasis, rosacea, atopic dermatitis(AD), seborrheic dermatitis(SD), diaper dermatitis(DD), and Malassezia folliculitis(MF).The skin microbiota, a complex and evolving community, undergoes changes in composition and function that can compromise the skin microbial barrier. These alterations induce water loss and abnormal lipid metabolism, contributing to the onset of ISDs. Additionally, microorganisms release toxins, like Staphylococcus aureus secreted α toxins and proteases, which may dissolve the stratum corneum, impairing skin barrier function and allowing entry into the bloodstream. Microbes entering the bloodstream activate molecular signals, leading to immune disorders and subsequent skin inflammatory responses. For instance, Malassezia stimulates dendritic cells(DCs) to release IL-12 and IL-23, differentiating into a Th17 cell population and producing proinflammatory mediators such as IL-17, IL-22, TNF-α, and IFN-α.This review offers new insights into the role of the human skin microbiota in ISDs, paving the way for future skin microbiome-specific targeted therapies.
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This review focuses on the potential ameliorative effects of polyphenolic compounds derived from human diet on hepatic diseases. It discusses the molecular mechanisms and recent advancements in clinical applications. Edible polyphenols have been found to play a therapeutic role, particularly in liver injury, liver fibrosis, NAFLD/NASH, and HCC. In the regulation of liver injury, polyphenols exhibit anti-inflammatory and antioxidant effects, primarily targeting the TGF-ß, NF-κB/TLR4, PI3K/AKT, and Nrf2/HO-1 signaling pathways. In the regulation of liver fibrosis, polyphenolic compounds effectively reverse the fibrotic process by inhibiting the activation of hepatic stellate cells (HSC). Furthermore, polyphenolic compounds show efficacy against NAFLD/NASH by inhibiting lipid oxidation and accumulation, mediated through the AMPK, SIRT, and PPARγ pathways. Moreover, several polyphenolic compounds exhibit anti-HCC activity by suppressing tumor cell proliferation and metastasis. This inhibition primarily involves blocking Akt and Wnt signaling, as well as inhibiting the epithelial-mesenchymal transition (EMT). Additionally, clinical trials and nutritional evidence support the notion that certain polyphenols can improve liver disease and associated metabolic disorders. However, further fundamental research and clinical trials are warranted to validate the efficacy of dietary polyphenols.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/patología , Carcinoma Hepatocelular/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Cirrosis Hepática/tratamiento farmacológico , Hígado/metabolismo , Vía de Señalización Wnt , DietaRESUMEN
BACKGROUND: Correa's cascade is a pathological process beginning from gastritis to gastric precancerous lesions, and finally to gastric carcinoma (GC). While the pathogenesis of GC remains unclear, oxidative stress plays a prominent role throughout the entire Correa's cascade process. Studies have shown that some natural products (NPs) could halt and even reverse the development of the Correa's cascade by targeting oxidative stress. METHODS: To review the effects and mechanism by which NPs inhibit the Correa's cascade through targeting oxidative stress, data were collected from PubMed, Embase, Web of Science, ScienceDirect, and China National Knowledge Infrastructure databases from initial establishment to April 2023. NPs were classified and summarized by their mechanisms of action. RESULTS: NPs, such as terpenoid, polyphenols and alkaloids, exert multistep antioxidant stress effects on the Correa's cascade. These effects include preventing gastric mucosal inflammation (stage 1), reversing gastric precancerous lesions (stage 2), and inhibiting gastric carcinoma (stage 3). NPs can directly impact the conversion of gastritis to GC by targeting oxidative stress and modulating signaling pathways involving IL-8, Nrf2, TNF-α, NF-κB, and ROS/MAPK. Among which polyphenols have been studied more and are of high research value. CONCLUSIONS: NPs display a beneficial multi-step action on the Correa's cascade, and have potential value for clinical application in the prevention and treatment of gastric cancer by regulating the level of oxidative stress.
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Productos Biológicos , Carcinoma , Gastritis , Lesiones Precancerosas , Neoplasias Gástricas , Humanos , Antioxidantes/farmacología , Productos Biológicos/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/prevención & control , Lesiones Precancerosas/complicaciones , Lesiones Precancerosas/patología , Carcinoma/complicacionesRESUMEN
The combustible defects of polyamide 6 (PA6), especially the flammable melt-dripping behavior, have greatly limited its application in some particular fields. In this work, a halogen-free hyperbranched polysiloxane (PBDSi) containing DOPO and Schiff base was designed via Michael's addition reaction and dehydration-condensation reaction. Results showed that the char yield (Yc) of PBDSi attained 37.9 wt%, confirming the satisfactory charring behavior of PBDSi for preparing flame-retardant PA6. Just by adding 3 wt% of PBDSi, the serious melt droplets of PA6 were suppressed effectively. The prepared PA6/PBDSi-3 with 5 wt% of PBDSi could achieve the highest value of limited oxygen index (LOI) of 27.2 %, while that of PA6 is 21.0 %. Meanwhile, PA6/PBDSi-3 obtained an apparent reduction in the peak heat release rate (PHRR) value of 31.1 % compared with pure PA6. The cooperated effect of DOPO, Schiff base, and polysiloxane that contributed to generating a silicon-phosphorous-rich char layer and releasing incombustible volatiles that were determined to be the essential factor for the improved fire safety of PA6/PBDSi were explored intensively. Inspiringly, PA6/PBDSi composites exhibited a slight mechanical loss concerning PA6, overcoming the great challenge of developing additive flame-retardant materials to balance mechanical properties and fire safety.