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The challenges generated by insufficient T cell activation and infiltration have constrained the application of immunotherapy. Making matters worse, the complex tumor microenvironment (TME), resistance to apoptosis collectively poses obstacles for cancer treatment. The carrier-free small molecular self-assembly strategy is a current research hotspot to overcome these challenges. This strategy can transform multiple functional agents into sustain-released hydrogel without the addition of any excipients. Herein, a coordination and hydrogen bond mediated tricomponent hydrogel (Cel hydrogel) composed of glycyrrhizic acid (GA), copper ions (Cu2+) and celastrol (Cel) was initially constructed. The hydrogel can regulate TME by chemo-dynamic therapy (CDT), which increases reactive oxygen species (ROS) in conjunction with GA and Cel, synergistically expediting cellular apoptosis. What's more, copper induced cuproptosis also contributes to the anti-tumor effect. In terms of regulating immunity, ROS generated by Cel hydrogel can polarize tumor-associated macrophages (TAMs) into M1-TAMs, Cel can induce T cell proliferation as well as activate DC mediated antigen presentation, which subsequently induce T cell proliferation, elevate T cell infiltration and enhance the specific killing of tumor cells, along with the upregulation of PD-L1 expression. Upon co-administration with aPD-L1, this synergy mitigated both primary and metastasis tumors, showing promising clinical translational value.
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Cobre , Hidrogeles , Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Activación de Linfocitos , Triterpenos Pentacíclicos , Especies Reactivas de Oxígeno , Linfocitos T , Microambiente Tumoral , Triterpenos Pentacíclicos/farmacología , Hidrogeles/química , Animales , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Inmunoterapia/métodos , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Ratones , Activación de Linfocitos/efectos de los fármacos , Cobre/química , Microambiente Tumoral/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Humanos , Ratones Endogámicos C57BL , Ácido Glicirrínico/farmacología , Ácido Glicirrínico/química , Femenino , Triterpenos/farmacología , Triterpenos/químicaRESUMEN
Studies have confirmed that the spatial arrangement of chiral molecules has a decisive influence on supramolecular assembly. However, the effect of epimerization caused by the change of a single chiral center on the self-assembly of chiral molecules has not been reported. Herein, we explored a pair of epimers 18 α-glycyrrhetinic acid and 18 ß-glycyrrhetinic acid from Glycyrrhiza uralensis Fisch, which had completely different medicinal activities. In this study, we found that these epimers of glycyrrhetinic acid showed distinct self-assembly properties under the condition of the deionized water and a small amount of DMSO solution. Interestingly, the cis-configured 18 ß-GA could form a 'head-to-tail' interlaced structure and further self-assembled to form nanoparticles, while trans-configured 18 α-GA was connected in a "head-to-head" manner, and due to the excessive steric hindrance that made it difficult to assemble. This work not only clearly demonstrates the impact of epimerization due to changes in a single chiral center on the self-assembly of chiral molecules as well as biological activity, but also provides new insights into the self-assembly of natural organic molecules in the development of nanomedicines and biofunctional materials.
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Antibacterianos , Ácido Glicirretínico , Ácido Glicirretínico/química , Ácido Glicirretínico/farmacología , Ácido Glicirretínico/análogos & derivados , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Estereoisomerismo , Pruebas de Sensibilidad Microbiana , Nanopartículas/química , Glycyrrhiza uralensis/química , Escherichia coli/efectos de los fármacos , Tamaño de la Partícula , Staphylococcus aureus/efectos de los fármacosRESUMEN
We examined the occurrence and levels of 19 legacy and emerging per- and polyfluoroalkyl substances (PFASs) in 7 species of marine bivalve molluscs collected from four coastal cities of Shandong Province, China. Perfluorooctanoic acid (PFOA) was the most prevalent component, accounting for 68.1 % of total PFASs. The total PFASs in bivalve molluscs ranged from 0.86 to 6.55 ng/g wet weight, with the highest concentration found in Meretrix meretrix L. The concentration of total PFASs in bivalve molluscs showed the following trend: clams > scallops > oysters > mussels. Estimation on the human intake of PFASs from consumption of bivalve molluscs resulted in hazard ratios (HR) ranging from 0.12 to 6.40. Five of the seven species had HR >1, indicating high exposure risks associated with PFASs. Therefore, the occurrence of PFASs in marine biota is particularly concerning and further investigations on the sources of PFASs in Shandong are warranted.
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Bivalvos , Monitoreo del Ambiente , Fluorocarburos , Contaminantes Químicos del Agua , Animales , China , Fluorocarburos/análisis , Contaminantes Químicos del Agua/análisis , Humanos , Caprilatos/análisisRESUMEN
BACKGROUND: Although hepatitis B virus infection is the leading cause of chronic liver injury globally, nonalcoholic fatty liver disease (NAFLD) is gradually gaining attention as another major chronic liver disease. The number of patients having chronic hepatitis B (CHB) with concomitant hepatic steatosis has increased. AIM: To analyze the effect of NAFLD on the response to antiviral treatment in patients with CHB. METHODS: Relevant English studies were systematically searched across PubMed, EMBASE, Web of Science, and Cochrane Library until October 2023. Studies in which the treatment outcomes were compared between patients with CHB only and those with CHB and hepatic steatosis were included. RESULTS: Of the 2502 retrieved studies, 11 articles were finally included. Biochemical response until 48 wk (OR = 0.87, 95%CI: 0.50-1.53, P = 0.000) and 96 wk (OR = 0.35, 95%CI: 0.24-0.53, P = 0.24) and virological response until 96 wk (OR = 0.80, 95%CI: 0.43-1.49, P = 0.097) were lower in patients with hepatic steatosis than in patients with CHB alone. CONCLUSION: Hepatic steatosis lowers the biochemical response to antiviral treatment in patients with CHB.
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(1) Background: Heterotrophs can affect plant biomass and alter species diversity-productivity relationships. However, these studies were conducted in systems with a low nitrogen (N) availability, and it is unclear how heterotroph removal affects the relationship between plant species diversity and productivity in different N habitats. (2) Methods: Three typical understory herbaceous plants were selected to assemble the plant species diversity (three plant species richness levels (1, 2, and 3) and seven plant species compositions), and the control, insecticide, fungicide, and all removal treatments were performed at each plant species diversity level in systems with or without N addition treatments. (3) Results: In systems without N addition, the insecticide treatment increased the plant aboveground biomass, total biomass, and leaf area, while the fungicide treatment reduced the plant belowground biomass, root length, and root tip number; the presence of Bidens pilosa increased the plant aboveground biomass. Similarly, the presence of Bletilla striata increased the plant belowground biomass and root diameter under each heterotroph removal treatment. In systems with N addition, all removal treatments reduced the plant belowground biomass and increased the plant leaf area; the presence of B. pilosa significantly increased the plant aboveground biomass, total biomass, and root length under each heterotroph removal treatment. The presence of B. striata significantly increased the plant belowground biomass and leaf area under insecticide and fungicide treatments. (4) Conclusions: Heterotroph removal alters the plant species diversity-biomass relationship by affecting the plant functional traits in systems with different N availabilities. The impact of biodiversity at different trophic levels on ecosystem functioning should be considered under the background of global change.
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BACKGROUND: Mahuang Fuzi decoction (MGF) is composed of three herb medicines that has been clinically used to treat inflammatory diseases for a long history. At present, more and more active phytochemicals' aggregations have been found during the thermodynamic process of herb medicine decoction, and revealing the clinical efficacy of herb medicine through supramolecular strategies is the focus of current research. However, it is not clear whether decoction induced supermolecules' morphological changes to modify activity. METHODS: Dynamic light scattering (DLS) and field emission scanning electron microscopy (FESEM) were used to analyze the micromorphology of MGF, MGF SA (MGF supermolecules), and MIX (physical mixture of MGF single decoction). The interaction and thermodynamic parameters of single herbs in a decoction were investigated by Isothermal titration calorimetry (ITC). The phytochemicals were systematically analyzed by ultra high performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS). Under the safe dose on RAW264.7 cells, NO, IL-6 and TNF-α were determined by Enzyme-Linked ImmunoSorbent Assay (ELISA) method. NF-κB p65 translocation from the cytoplasm into the nucleus was examined using the immunofluorescence assay and the western blot, respectively. Furthermore, Metabolomics was used to discover potential biomarkers and the associated metabolic pathways of MGF SA treatment. RESULTS: There were nanoscale aggregations in MGF, and the micromorphology of the extracted MGF SA consisted of uniform particles; while the MIX micromorphology had no uniformity. ITC showed that the interaction MH-GC and FZ-GC were a spontaneous exothermic reaction, indicating that their phytochemicals had the property of self-assembly. Though the micromorphology between MGF, MGF SA, and MIX was obviously different, UHPLC-Q-Orbitrap HRMS results displayed that the main phytochemicals of MGF and MIX had nearly the same components. Interestingly, MGF and MGF SA could significantly inhibit the production of NO, and had better inhibition effect on the expression of nuclear protein NF-κB p65 than MIX, among which MGF SA had the best effect. Further investigation indicated that the perturbance of metabolic profiling in RAW264.7 inflammatory cells was obviously reversed by MGF SA. CONCLUSIONS: The decoction enriched the key active phytochemicals and regulated the formation of homogeneous nanoparticles in MGF SA. The supermolecules in MGF SA significantly enhanced its anti-inflammatory activity, primarily affecting the NF-κB signaling pathway and the biosynthesis and metabolism of arginine in RAW264.7 inflammatory cells. Current study displayed that co-decocting herbal medicine were beneficial to the treatment of diseases than the mixture of the single herbs' extraction.
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In this study 13 heavy metals were analysed in representative livestock meat, poultry meat, livestock offal and poultry offal samples (20 per category) from marketplaces and retail stores in 16 cities in Shandong province, China. The investigated heavy metals were Cu, Cr, V, Ni, As, Se, Sn, Cd, Pb, Sb, Mn, Ba and Hg. Results revealed mean levels of total heavy metals in meat and offal of 1.56 mg/kg and 39.8 mg/kg, respectively. Cu, Cr, Mn, Ni, Se, Ba and Pb were found in all samples (100%), followed by Hg (95.0%), V (91.3%), Sn (73.8%), Cd (51.3%), As (21.3%) and Sb (11.3%). Hazard Quotient (HQ) and Hazard Index (HI) values showed that high meat intake can cause potential health risks. Thus, continuous monitoring of health risks and trends of heavy metals in meat products is needed, both for food safety and consumer's health.
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Productos de la Carne , Mercurio , Metales Pesados , Contaminantes del Suelo , Monitoreo del Ambiente/métodos , Productos de la Carne/análisis , Cadmio/análisis , Plomo/análisis , Contaminación de Alimentos/análisis , Contaminantes del Suelo/análisis , Metales Pesados/análisis , Mercurio/análisis , Medición de Riesgo , ChinaRESUMEN
Sporadic synchronous colorectal cancer (SCRC) refers to multiple primary CRC tumors detected simultaneously in an individual without predisposing hereditary conditions, which accounts for the majority of multiple CRCs while lacking a profound understanding of the genomic landscape and evolutionary dynamics to optimize its treatment. In this study, 103 primary tumor samples from 51 patients with SCRC undergo whole-exome sequencing. The germline and somatic mutations and evolutionary and clinical features are comprehensively investigated. Somatic genetic events are largely inconsistent between paired tumors. Compared with solitary CRC, SCRCs have higher prevalence of tumor mutation burden high (TMB-H; 33.3%) and microsatellite-instability high (MSI-H; 29.4%) and different mutation frequencies in oncogenic signaling pathways. Moreover, neutrally evolving SCRC tumors are associated with higher intratumoral heterogeneity and better prognosis. These findings unveil special molecular features, carcinogenesis, and prognosis of sporadic SCRC. Strategies for targeted therapy and immunotherapy should be optimized accordingly.
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Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/terapia , Inestabilidad de Microsatélites , Pronóstico , Biomarcadores de Tumor/genética , GenómicaRESUMEN
We investigated the distribution of 8 per- and polyfluoroalkyl substances (PFASs) in 321 shellfish samples collected from four coastal cities along the Yellow Sea and Bohai Sea of Shandong Province, China. The concentrations of total PFASs (∑PFASs) were in the range of 0.061-178.259 ng/g wet weight (ww). Two legacy long-chain compounds were dominant. Three emerging compounds and two short-chain alternatives were also observed with higher concentration and detection frequency than in previous studies, whereas 4, 8-dioxa-3H-perfluorononanoate acid (ADONA) was not detected. There were differences in concentrations and composition profiles of PFASs among different species, as well as among different sampling cities. According to scores of principal component analysis, metal plating plants, textile treatments, and fluoropolymer products were considered as the main sources of PFAS contamination in shellfish. Furthermore, a potential health risk of perfluorooctanoic acid should be highly considered for local residents that frequently consume crabs and molluscs.
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Chronic hepatitis B (CHB) and hepatic steatosis (HS) are two prevalent chronic liver diseases in Asia. The incidence of CHB combined with HS is increasing due to the rising obesity rates. However, the impact of HS on CHB remains a topic of debate. Hereby, this meta-analysis aims to examine the effect of HS on Asian patients with CHB. Searches were conducted on four databases to identify articles published from 2005 to 2023. The random-effects or fixed-effects model was used to calculate pooled odds ratios (ORs), weighted mean difference (WMD), and confidence intervals (CIs) for the included articles. Of the 15,959 records screened, 88 studies were included in the analysis of HS prevalence in Asian CHB patients with a prevalence of 36.5% (95% CI: 33.7%-39.3%). In addition, age, sex, body mass index (BMI), waist circumference (WC), alanine aminotransferase (ALT) and combined metabolic diseases have varying degrees of impact on HS in CHB patients. Furthermore, the coexistence of HS was negatively associated with the response to antiviral therapy, including hepatitis B surface antigen (HBeAg) seroconversion (OR = 0.69, 95% CI: 0.53-0.89) and ALT normalization (OR = 0.75, 95% CI: 0.61-0.92) in CHB patients after 48 weeks of treatment. Regarding disease prognosis, HS was not significantly associated with fibrosis or cirrhosis in CHB patients, while an inverse association was observed between HS and hepatocellular carcinoma (HCC) (OR = 2.93, 95% CI: 1.23-6.99). This implies that the coexistence of HS in CHB patients may exacerbate the progression of HCC, which needs to be verified by further studies.
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Carcinoma Hepatocelular , Hígado Graso , Hepatitis B Crónica , Neoplasias Hepáticas , Humanos , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/epidemiología , Hepatitis B Crónica/tratamiento farmacológico , Carcinoma Hepatocelular/etiología , Neoplasias Hepáticas/epidemiología , Hígado Graso/complicaciones , Hígado Graso/epidemiología , Hígado Graso/patología , Cirrosis Hepática/epidemiología , Cirrosis Hepática/complicaciones , Fibrosis , Asia/epidemiología , Virus de la Hepatitis BRESUMEN
Acupuncture can alleviate depression-like behaviors. However, the neural mechanisms behind the anti-depressive effect remain unknown. Perineuronal net (PNN) abnormalities have been reported in multiple psychiatric disorders. This study investigated the modulation and neural mechanism of PNNs in the anti-depressant process of electroacupuncture (EA) at Baihui (GV20) and Yintang (GV29) points. A rat depression model was induced by chronic unpredicted mild stress (CUMS). The results revealed that CUMS, applied for four weeks, specifically reduces PNNs around parvalbumin (PV). In addition, EA and fluoxetine treatments reverse the decrease in PNNs+ cell density and the ratio of PV and PNN double-positive cells to PV+ neurons in the medial prefrontal cortex (mPFC) after CUMS. Furthermore, EA treatment can reverse the decrease in the protein expression of PNN components (aggrecan and brevican) in the mPFC caused by stress. After EA treatment, the decreased expression of GAD67, GLuA1, and PSD95 in the mPFC induced by CUMS for four weeks was also reversed. PNN degradation in mPFC brain areas potentially interferes with the anti-depressant benefits of EA in rats with depression induced by CUMS. EA treatment did not increase PNNs+ cell density and the ratio of PV and PNN double-positive cells to PV+ neurons after PNNs degradation in the mPFC brain region of rats. This finding indicated that the mechanism of acupuncture's anti-depressant effect may be based on reversing the CUMS-induced decline in PNN expression, the functional impairment of γ-aminobutyric acid (GABA) neurons, and the regulation of excitatory synaptic proteins expression.
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Depresión , Electroacupuntura , Ratas , Animales , Depresión/terapia , Neuronas/metabolismo , Matriz Extracelular/metabolismo , Corteza Cerebral/metabolismo , Parvalbúminas/metabolismoRESUMEN
ABSTRACT: The intestinal mucus layer is a barrier that separates intestinal contents and epithelial cells, as well as acts as the "mucus layer-soil" for intestinal flora adhesion and colonization. Its structural and functional integrity is crucial to human health. Intestinal mucus is regulated by factors such as diet, living habits, hormones, neurotransmitters, cytokines, and intestinal flora. The mucus layer's thickness, viscosity, porosity, growth rate, and glycosylation status affect the structure of the gut flora colonized on it. The interaction between "mucus layer-soil" and "gut bacteria-seed" is an important factor leading to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Probiotics, prebiotics, fecal microbiota transplantation (FMT), and wash microbial transplantation are efficient methods for managing NAFLD, but their long-term efficacy is poor. FMT is focused on achieving the goal of treating diseases by enhancing the "gut bacteria-seed". However, a lack of effective repair and management of the "mucus layer-soil" may be a reason why "seeds" cannot be well colonized and grow in the host gut, as the thinning and destruction of the "mucus layer-soil" is an early symptom of NAFLD. This review summarizes the existing correlation between intestinal mucus and gut microbiota, as well as the pathogenesis of NAFLD, and proposes a new perspective that "mucus layer-soil" restoration combined with "gut bacteria-seed" FMT may be one of the most effective future strategies for enhancing the long-term efficacy of NAFLD treatment.
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Microbioma Gastrointestinal , Enfermedad del Hígado Graso no Alcohólico , Probióticos , Humanos , Enfermedad del Hígado Graso no Alcohólico/terapia , Prebióticos , Trasplante de Microbiota Fecal , Bacterias , Hígado/patologíaRESUMEN
The polysaccharides (FP) extracted from the lateral roots of Aconitum carmichaelii Debx. (Fuzi) are natural compounds, which have effective therapy for rheumatoid arthritis (RA). Methotrexate (MTX) is the first-line drug for RA, but its application is greatly limited to the toxicity in liver and kidney and drug resistance. In this study, an attempt is made to apply oxidized FP (OFP) as a polymer carrier based on intra-articular delivery system loaded MTX. The FP could be modified and used as comprehensive gel carriers with biocompatibility and degradability for therapy of RA. Firstly, OFP-chitosan-poloxamer 407 in situ gel (OFP-CS-F407-MTX gel) was prepared by natural non-toxic cross-linking agents. Physicochemical characterization was performed by using 1H NMR and FTIR spectroscopic techniques to assess the successful functionalization of OFP. TGA, SEM and rheological experiment of OFP-CS-F407-MTX gel were investigated. Notably, we loaded MTX into OFP-CS-F407-MTX gel which had remarkable therapeutic efficacy and biosafety for RA. Therefore, OFP-CS-F407-MTX in situ gel delivery system can potentially reduce systemic toxicity and irritation of oral administration of MTX but hold a controlled release of drug for a long period of time.
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Aconitum , Artritis Reumatoide , Metotrexato/química , Aconitum/química , Artritis Reumatoide/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Polisacáridos/uso terapéuticoRESUMEN
Background: The relative efficacy of 5 sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and 4 glucagon-like peptide-1 (GLP-1) receptor agonists for non-alcoholic fatty liver disease (NAFLD) therapy has not been sufficiently investigated. Methods: Randomized controlled trials (RCTs) in which patients with NAFLD were treated with SGLT-2 inhibitors or GLP-1 receptor agonists were included. Primary outcomes were improvements in liver enzymes and liver fat parameters, while secondary outcomes included anthropometric measures, blood lipids and glycemic parameters. The frequentist method was used to perform a network meta-analysis. Evidence certainty was assessed using the grading of recommendations assessment, development, and evaluation (GRADE). Results: The criteria were satisfied by 37 RCTs with 9 interventions (5 SGLT-2 inhibitors and 4 GLP-1 receptor agonists). Based on high certainty evidence, in patients with NAFLD (or comorbid with type 2 diabetes), semaglutide could lower alanine aminotransferase as well as aspartate aminotransferase, γ-glutamyl transferase, controlled attenuation parameter, liver stiffness measurement, body weight, systolic blood pressure, triglycerides, high-density lipoprotein-cholesterol, glycosylated hemoglobin. Liraglutide could lower alanine aminotransferase as well as subcutaneous adipose tissue, body mass index, fasting blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment, while dapagliflozin could lower alanine aminotransferase as well as body weight, fasting blood glucose, postprandial blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment. Conclusion: Semaglutide, liraglutide, and dapagliflozin all have a certain effect on NAFLD (or comorbid with type 2 diabetes) based on high confidence evidence from indirect comparisons, and semaglutide appears to have a therapeutic advantage over the other included medicines. Head-to-head studies are needed to provide more confidence in clinical decision-making.
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INTRODUCTION: There is no conclusive evidence comparing the efficacy of glucagon-like peptide 1 (GLP-1) receptor agonists to the other guidelines recommended pharmacotherapy for nonalcoholic fatty liver disease (NAFLD). Therefore, we aim to compare the effects of GLP-1 receptor agonists, pioglitazone and vitamin E in patients with NAFLD. METHODS: We searched PubMed, Embase, Web of Science and Cochrane Library up to 11 April 2022. Randomized clinical trials (RCTs) comparing GLP-1 receptor agonists, pioglitazone and vitamin E against placebo or other active controls in patients with NAFLD were included. RESULTS: Nine RCTs including 1482 patients proved eligible. GLP-1 receptor agonists ranked first in steatosis, ballooning necrosis, γ-glutamyl transferase, body weight, body mass index, and triglycerides. Administration of GLP-1 receptor agonists, as compared with placebo, was associated with improvement in liver histology [steatosis (OR = 4.11, 95% CI: 2.83, 5.96), ballooning necrosis (OR = 3.07, 95% CI: 2.14, 4.41), lobular inflammation (OR = 1.86, 95% CI: 1.29, 2.68), fibrosis (OR = 1.52, 95% CI: 1.06, 2.20)]. CONCLUSIONS: GLP-1 receptor agonists were as effective as pioglitazone and vitamin E for liver histology among patients with NAFLD. GLP-1 receptor agonists might be considered as an alternative or complementary treatment in the future clinical practice. [Figure: see text].
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Diabetes Mellitus Tipo 2 , Enfermedad del Hígado Graso no Alcohólico , Humanos , Péptido 1 Similar al Glucagón/uso terapéutico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Receptor del Péptido 1 Similar al Glucagón/uso terapéutico , Hipoglucemiantes/efectos adversos , Necrosis/tratamiento farmacológico , Metaanálisis en Red , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/patología , Pioglitazona/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Vitamina E/efectos adversos , Proyectos PilotoRESUMEN
AMP-activated protein kinase (AMPK) regulates overall energy consumption and energy intake through cytokines. Ligusticum striatum DC (CX) combined with Gastrodia elata Blume (TM) has been used for migraine treatment for millennia. When used alone in clinical practice, CX causes symptoms of thirst, irritability, and yellow urine and has influenced the levels of cytokines such as AMP that activate the AMPK pathway of energy metabolism. However, relationships between this compatibility prescription, integral biological energy metabolism, and the AMPK pathway remain unclear. Studies were performed by treating normal rats with physiological saline, CX extract, CX coupled TM extract, and TM extracts separately for 4 weeks. Food intake, water intake, urine output, stool output, and body weight were monitored once a week by the metabolic cage method. Values of FBG, BUN, TP, TC and TG in blood samples were detected approaching the whole blood automatic detector from 1 to 4 weeks. Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, cAMP, and cGMP activity were determined by the enzyme-linked immunosorbent assay (ELISA); the biological samples that were obtained at 1, 2, 3, and 4 weeks after drug administration were tested by GC-TOF-MS. Then real-time PCR and Western Blot were applied to detect changes in expression of some substances involved in energy metabolism. The results demonstrated that administering CX alone increased energy input, mobility, and respiratory exchange ratio, accelerated energy consumption, and caused inflammatory infiltration in the liver. CX coupled with TM led to lower energy metabolism and liver damage in comparison with CX used alone. Moreover, CX-treated rats harbored higher levels of differential metabolites (including pyrophosphate, oxaloacetic acid, and galactinol). Glycerophospholipid metabolism and the citrate cycle are closely related to the differential metabolites above. In addition, CX-induced unbalanced energy metabolism depends on cAMP activation mediated by the AMPK/PGC-1α pathway in rats. Our findings suggest that CX-induced energy metabolism imbalance was corrected after coupling with TM by mediating the AMPK/PGC-1α pathway.
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OBJECTIVE: To investigate the contamination of 2-chloropropanol esters and 3-chloropropanol esters in commercial edible vegetable oils in Shandong Province, and to assess the dietary 3-chloropropanol esters exposure and the health risk of intaking 3-chloropropanol esters. METHODS: From 2016 to 2020, 406 individually packaged edible vegetable oils were collected from stores and farmers' markets in 16 prefecture-level cities in Shandong Province. According to the 2016 National Food Contamination and Harmful Factors Risk Monitoring Manual, using gas chromatography-triple quadrupole tandem mass spectrometry detection, isotope internal standard method for quantification, laboratory determination of 2-chloropropanol ester and 3-chloropropanol in vegetable oil ester content. Combined with population weight, oil consumption and monitoring data, the point assessment method was used to evaluate the exposure of residents in Shandong Province to 3-chloropropanol esters. RESULTS: The detection rate of 3-chloropropanol ester was 92.4%(375/406), the concentration range was<limit of detection(LOD)-18.4 mg/kg, the median was 0.470 mg/kg, the average was 0.833 mg/kg, and the maximum value was 18.4 mg/kg in rice oil; the detection rate of 2-chloropropanol ester was 88.7%(360/406), the concentration range was <LOD-8.46 mg/kg, the median value was 0.204 mg/kg, the average value was 0.432 mg/kg, and the maximum value was 8.46 mg/kg in rice oil. The average exposure of each age group was less than the tolerable daily intake, and the high-end exposure of the children(2-6 years old) and adolescents(7-10 years old) group was greater than the tolerable daily intake. CONCLUSION: The contamination of chloropropanol esters of edible vegetable oil in Shandong Province from 2016 to 2020 is widespread, and the highest detection value appears in rice oil. Children(2-6 years old) and adolescents(7-10 years old) in high-risk situations ingest 3-chloropropanol esters present health risks.
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Ésteres , Aceites de Plantas , Adolescente , Niño , Preescolar , Ésteres/análisis , Contaminación de Alimentos/análisis , Cromatografía de Gases y Espectrometría de Masas , Humanos , Isótopos/análisis , Aceites de Plantas/química , VerdurasRESUMEN
Background: Psychiatric disorders have seriously affected human life, one of the risk genes related to psychosis is the methylenetetrahydrofolatereductase (MTHFR) gene. This gene has a potential role in psychiatric disorders. Therefore, a meta-analysis is conducted to investigate the correlations between two prevalent MTHFR single nucleotide polymorphisms (SNPs), MTHFR C677T, A1298C, severe psychological disorders (schizophrenia, major depression, bipolar disorder). Methods: A total of 81 published studies were screened and selected by a search of electronic databases up to April 2022. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between MTHFR polymorphism and psychiatric disorders susceptibility by using random effect models. Results: We found that MTHFR C677T polymorphism is significantly related to schizophrenia and major depression in the overall population. MTHFR C677T has been linked to an increased risk of bipolar disorder in the recessive model (TT vs. CT + CC). Ethnic subgroup analysis shows that schizophrenia and major depression significantly correlate with MTHFR C677T and A1298C in Asian populations but not Caucasians. Besides, schizophrenia is correlated substantially with MTHFR C677T in the African population. However, the MTHFR A1298C polymorphism is only marginally linked to major depression. Conclusion: Findings of the current study revealed that MTHFR may contribute to the common pathogenesis of psychiatric diseases and that its variants may be essential in controlling the expression of psychosis-related genes. This study could help the researchers and health specialists in the early diagnosis and treatment of psychiatric disorders.
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[This retracts the article DOI: 10.21037/tp-22-68.].
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Background: This study aimed to evaluate the effect of mineral trioxide aggregate (MTA) pulp capping for caries-exposed permanent teeth. However, the efficacy of MTA in the treatment of children's gums is still controversial, and different studies have shown different efficacy. Therefore, it is necessary to systematically review the efficacy and safety of MTA pulp incision in the treatment of pediatric caries using meta methods. Methods: We used meta-analysis to compare differences in the efficacy of MTA and calcium hydroxide (CH) for treating caries in permanent teeth. The mean treatment success rate of MTA for reversible and irreversible pulpitis groups was calculated, and the effect of apical opening condition and surgical type on success rate were investigated. Results: A total of 15 studies were included, and meta-analysis showed that there was a significant statistical difference between the MTA group and CH group in efficacy [odds ratio (OR) =1.87, 95% confidence interval (CI): 1.28, 2.73, P=0.001, I2=63%, Z=3.25], success rate (OR =3.20, 95% CI: 1.93, 5.30, P<0.00001, I2=0%, Z=4.52), influence of apical foramen condition on success rate (OR =1.77, 95% CI: 1.14, 2.73, P=0.01, I2=15%, Z=2.56), and surgical procedure on success rate (OR =2.64, 95% CI: 1.65, 4.23, P<0.0001, I2=45%, Z=4.05). Discussion: Our results showed that MTA pulpotomy was superior to CH. Nonclosure of apical openings and complete coronal pulpotomy may be more beneficial than partial pulpotomy.