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The present study aimed to investigate the effect of diosgenin on mammalian target of rapamycin(mTOR), fatty acid synthase(FASN), hypoxia inducible factor-1α(HIF-1α), and vascular endothelial growth factor A(VEGFA) expression in liver tissues of rats with non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin on lipogenesis and inflammation in NAFLD. Forty male SD rats were divided into a normal group(n=8) fed on the normal diet and an experimental group(n=32) fed on the high-fat diet(HFD) for the induction of the NAFLD model. After modeling, the rats in the experimental group were randomly divided into an HFD group, a low-dose diosgenin group(150 mg·kg~(-1)·d~(-1)), a high-dose diosgenin group(300 mg·kg~(-1)·d~(-1)), and a simvastatin group(4 mg·kg~(-1)·d~(-1)), with eight rats in each group. The drugs were continuously given by gavage for eight weeks. The levels of triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were detected by the biochemical method. The content of TG and TC in the liver was detected by the enzyme method. Enzyme-linked immunosorbent assay(ELISA) was used to measure interleukin 1ß(IL-1ß) and tumor necrosis factor α(TNF-α) in the serum. Lipid accumulation in the liver was detected by oil red O staining. Pathological changes of liver tissues were detected by hematoxylin-eosin(HE) staining. The mRNA and protein expression levels of mTOR, FASN, HIF-1α, and VEGFA in the liver of rats were detected by real-time fluorescence-based quantitative polymerase chain reaction(PCR) and Western blot, respectively. Compared with the normal group, the HFD group showed elevated body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1ß, and TNF-α(P<0.01), increased lipid accumulation in the liver(P<0.01), obvious liver steatosis, up-regulated mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.01), and increased protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). Compared with the HFD group, the groups with drug treatment showed lowered body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1ß, and TNF-α(P<0.05, P<0.01), reduced lipid accumulation in the liver(P<0.01), improved liver steatosis, decreased mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.05, P<0.01), and declining protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). The therapeutic effect of the high-dose diosgenin group was superior to that of the low-dose diosgenin group and the simvastatin group. Diosgenin may reduce liver lipid synthesis and inflammation and potentiate by down-regulating the mTOR, FASN, HIF-1α, and VEGFA expression, playing an active role in preventing and treating NAFLD.
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Hepatopatia Gordurosa não Alcoólica , Ratos , Masculino , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , LDL-Colesterol , Ratos Sprague-Dawley , Fígado , Inflamação/metabolismo , Dieta Hiperlipídica/efeitos adversos , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , RNA Mensageiro/metabolismo , Peso Corporal , MamíferosRESUMO
This study aims to observe the effects of diosgenin on the expression of mammalian target of rapamycin(mTOR), sterol regulatory element-binding protein-1c(SREBP-1c), heat shock protein 60(HSP60), medium-chain acyl-CoA dehydrogenase(MCAD), and short-chain acyl-CoA dehydrogenase(SCAD) in the liver tissue of the rat model of non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin in alleviating NAFLD. Forty male SD rats were randomized into five groups: a control group, a model group, low-(150 mg·kg~(-1)·d~(-1)) and high-dose(300 mg·kg~(-1)·d~(-1)) diosgenin groups, and a simvastatin(4 mg·kg~(-1)·d~(-1)) group. The rats in the control group were fed with a normal diet, while those in the other four groups were fed with a high-fat diet. After feeding for 8 weeks, the body weight of rats in the high-fat diet groups increased significantly. After that, the rats were administrated with the corresponding dose of diosgenin or simvastatin by gavage every day for 8 weeks. The levels of triglyceride(TG), total cholesterol(TC), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were determined by the biochemical method. The levels of TG and TC in the liver were measured by the enzyme method. Oil-red O staining was employed to detect the lipid accumulation, and hematoxylin-eosin(HE) staining to detect the pathological changes in the liver tissue. The mRNA and protein levels of mTOR, SREBP-1c, HSP60, MCAD, and SCAD in the liver tissue of rats were determined by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. Compared with the control group, the model group showed increased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lipid deposition in the liver, obvious hepatic steatosis, up-regulated mRNA and protein expression levels of mTOR and SREBP-1c, and down-regulated mRNA and protein expression levels of HSP60, MCAD, and SCAD. Compared with the model group, the rats in each treatment group showed obviously decreased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lessened lipid deposition in the liver, ameliorated hepatic steatosis, down-regulated mRNA and protein le-vels of mTOR and SREBP-1c, and up-regulated mRNA and protein levels of HSP60, MCAD, and SCAD. The high-dose diosgenin outperformed the low-dose diosgenin and simvastatin. Diosgenin may prevent and treat NAFLD by inhibiting the expression of mTOR and SREBP-1c and promoting the expression of HSP60, MCAD, and SCAD to reduce lipid synthesis, improving mitochondrial function, and promoting fatty acid ß oxidation in the liver.
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Diosgenina , Hepatopatia Gordurosa não Alcoólica , Ratos , Masculino , Animais , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Dieta Hiperlipídica/efeitos adversos , Diosgenina/metabolismo , Chaperonina 60/metabolismo , Chaperonina 60/farmacologia , Chaperonina 60/uso terapêutico , Ratos Sprague-Dawley , Fígado , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Triglicerídeos , RNA Mensageiro/metabolismo , Sinvastatina/metabolismo , Sinvastatina/farmacologia , Sinvastatina/uso terapêutico , Peso Corporal , Metabolismo dos Lipídeos , Mamíferos/genética , Mamíferos/metabolismoRESUMO
Diosgenin, a steroidal saponin, is a natural product found in many plants. Diosgenin has a wide range of pharmacological activities, and has been used to treat cancer, nervous system diseases, inflammation, and infections. Numerous studies have shown that diosgenin has potential therapeutic value for lipid metabolism diseases via various pathways and mechanisms, such as controlling lipid synthesis, absorption, and inhibition of oxidative stress. These mechanisms and pathways have provided ideas for researchers to develop related drugs. In this review, we focus on data from animal and clinical studies, summarizing the toxicity of diosgenin, its pharmacological mechanism, recent research advances, and the related mechanisms of diosgenin as a drug for the treatment of lipid metabolism, especially in obesity, hyperlipidemia, nonalcoholic fatty liver disease, atherosclerosis, and diabetes. This systematic review will briefly describe the advantages of diosgenin as a potential therapeutic drug and seek to enhance our understanding of the pharmacological mechanism, recipe-construction, and the development of novel therapeutics against lipid metabolism diseases.
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Diosgenina , Animais , Diosgenina/farmacologia , Diosgenina/uso terapêutico , Metabolismo dos Lipídeos , Estresse Oxidativo , Antioxidantes/farmacologia , Inflamação/tratamento farmacológicoRESUMO
The improvement of the capability of poly(N-isopropylacrylamide) (PNIPAAm) hydrogel coating in cell adhesion and detachment is critical to efficiently prepare cell sheets applied in cellular therapies and tissue engineering. To enhance cell response on the surface, the amine group-modified PNIPAAm (PNIPAAm-APTES) nanohydrogels were synthesized and deposited spontaneously on tannic acid (TA)-modified polyethylene (PE) plates. Subsequently, TA was introduced onto PNIPAAm-APTES nanohydrogels to fabricate coatings composed of TA-modified PNIPAAm-APTES (PNIPAAm-APTES-TA). Characterization techniques, including TEM, SEM, XPS, and UV-Vis spectroscopy, confirmed the effective deposition of hydrogels of PNIPAAm as well as the morphologies, content of chemical bonding-TA, and stability of various coatings. Importantly, the porous hydrogel coatings exhibited superhydrophilicity at 20 °C and thermo-responsive behavior. The fluorescence measurement demonstrated that the coating's stability effectively regulated protein behavior, influencing cell response. Notably, cell response tests revealed that even without precise control over the chain length/thickness of PNIPAAm during synthesis, the coatings enhanced cell adhesion and detachment, facilitating efficient cell culture. This work represented a novel and facile approach to preparing bioactive PNIPAAm for cell culture.
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With the acceleration of people's pace of life, non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in the world, which greatly threatens people's health and safety. Therefore, there is still an urgent need for higher-quality research and treatment in this area. Nuclear factor Red-2-related factor 2 (Nrf2), as a key transcription factor in the regulation of oxidative stress, plays an important role in inducing the body's antioxidant response. Although there are no approved drugs targeting Nrf2 to treat NAFLD so far, it is still of great significance to target Nrf2 to alleviate NAFLD. In recent years, studies have reported that many natural products treat NAFLD by acting on Nrf2 or Nrf2 pathways. This article reviews the role of Nrf2 in the pathogenesis of NAFLD and summarizes the currently reported natural products targeting Nrf2 or Nrf2 pathway for the treatment of NAFLD, which provides new ideas for the development of new NAFLD-related drugs.
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Produtos Biológicos , Fator 2 Relacionado a NF-E2 , Hepatopatia Gordurosa não Alcoólica , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Humanos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Animais , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/uso terapêuticoRESUMO
Atherosclerosis is now widely considered to be a chronic inflammatory disease, with increasing evidence suggesting that lipid alone is not the main factor contributing to its development. Rather, atherosclerotic plaques contain a significant amount of inflammatory cells, characterized by the accumulation of monocytes and lymphocytes on the vessel wall. This suggests that inflammation may play a crucial role in the occurrence and progression of atherosclerosis. As research deepens, other pathological factors have also been found to influence the development of the disease. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is a recently discovered target of inflammation that has gained attention in recent years. Numerous studies have provided evidence for the causal role of this pathway in atherosclerosis, and its downstream signaling factors play a significant role in this process. This brief review aims to explore the crucial role of the JAK/STAT pathway and its representative downstream signaling factors in the development of atherosclerosis. It provides a new theoretical basis for clinically affecting the development of atherosclerosis by interfering with the JAK/STAT signaling pathway.
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Aterosclerose , Janus Quinases , Fatores de Transcrição STAT , Transdução de Sinais , Humanos , Aterosclerose/metabolismo , Aterosclerose/tratamento farmacológico , Fatores de Transcrição STAT/metabolismo , Janus Quinases/metabolismo , Animais , Inibidores de Janus Quinases/uso terapêutico , Inibidores de Janus Quinases/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Mediadores da Inflamação/metabolismoRESUMO
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and has no approved treatment. The hepatic farnesoid X receptor (FXR) is one of the most promising therapeutic targets for NAFLD. Diosgenin (DG), a natural compound extracted from Chinese herbal medicine, is very effective in preventing metabolic diseases. Our research aims to determine the effects and molecular mechanisms of DG on NAFLD in vivo and in vitro. The effect of DG on hepatic steatosis was evaluated in SpragueâDawley (SD) rats induced by a high-fat diet (HFD) and in HepG2 cells exposed to free fatty acids (FFAs, sodium oleate:sodium palmitate = 2:1). DG treatment efficiently managed hepatic lipid deposition in vivo and in vitro. Mechanistically, DG upregulated the expression of FXR and small heterodimer partner (SHP) and downregulated the expression of genes involved in hepatic de novo lipogenesis (DNL), including sterol regulatory element-binding protein 1C (SREBP1C), acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FASN). Moreover, DG promoted the expression of peroxisome proliferator-activated receptor alpha (PPARα), which is related to fatty acid oxidation. In addition, DG inhibited the expression of the CD36 molecule (CD36) related to fatty acid uptake. However, hepatic FXR silencing weakened the regulatory effects of DG on these genes. Collectively, our data show that DG has a good effect on alleviating nonalcoholic hepatic steatosis via the hepatic FXR-SHP-SREBP1C/PPARα/CD36 pathway. DG promises to be a novel candidate FXR activator that can be utilized to treat NAFLD.
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Diosgenina , Hepatopatia Gordurosa não Alcoólica , Animais , Ratos , Ácidos Graxos/metabolismo , Ácidos Graxos não Esterificados/farmacologia , Fígado , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , PPAR alfa/genética , PPAR alfa/metabolismo , Ratos Sprague-Dawley , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Diosgenina/uso terapêuticoRESUMO
Non-alcoholic fatty liver disease(NAFLD) is an umbrella term for a range of diseases ranging from hepatic fat accumulation and steatosis to non-alcoholic steatohepatitis (NASH) in the absence of excessive alcohol consumption and other definite liver damage factors. The incidence of NAFLD has increased significantly in recent years and will continue to grow in the coming decades. NAFLD has become a huge health problem and economic burden. SIRT1 is a member of Sirtuins, a group of highly conserved histone deacetylases regulated by NAD+, and plays a vital role in regulating cholesterol and lipid metabolism, improving oxidative stress, inflammation, and insulin resistance through deacetylating some downstream transcription factors and thus improving NAFLD. Although there are no currently approved drugs for treating NAFLD and some unresolved limitations in developing SIRT1 activators, SIRT1 holds promise as a proper therapeutic target for NAFLD and other metabolic diseases. In recent years, natural products have played an increasingly important role in drug development due to their safety and efficacy. It has been discovered that some natural products may be able to prevent and treat NAFLD by targeting SIRT1 and its related pathways. This paper reviews the mechanism of SIRT1 in the improvement of NALFD and the natural products that regulate NAFLD through SIRT1 and its associated pathways, and discusses the potential of SIRT1 as a therapeutic target for treating NAFLD and the effectiveness of these related natural products as clinical drugs or dietary supplements. These works may provide some new ideas and directions for finding new therapeutic targets for NAFLD and the development of anti-NAFLD drugs with good pharmacodynamic properties.
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The lack of physical activity has become a rigorous challenge for many countries, and the relationship between physical activity and the built environment has become a hot research topic in recent decades. This study uses the Strava Heatmap (novel crowdsourced data) to extract the distribution of cycling and running tracks in central Chengdu in December 2021 (during the COVID-19 pandemic) and develops spatial regression models for numerous 500 × 500 m grids (N = 2,788) to assess the impacts of the built environment on the cycling and running intensity indices. The findings are summarized as follows. First, land-use mix has insignificant effects on the physical activity of residents, which largely contrasts with the evidence gathered from previous studies. Second, road density, water area, green space area, number of stadiums, and number of enterprises significantly facilitate cycling and running. Third, river line length and the light index have positive associations with running but not with cycling. Fourth, housing price is positively correlated with cycling and running. Fifth, schools seem to discourage these two types of physical activities during the COVID-19 pandemic. This study provides practical implications (e.g., green space planning and public space management) for urban planners, practitioners, and policymakers.
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COVID-19 , Crowdsourcing , Ambiente Construído , COVID-19/epidemiologia , China , Planejamento Ambiental , Exercício Físico , Humanos , PandemiasRESUMO
Aims: The transport of patients suspected of having COVID-19 requires careful consideration. Using paths selected at random and not accounting for person flow along the path are risk factors for infection spread. Intrahospital transportation (IHT) protocols and guidelines should be used to help reduce the risk of secondary virus transmission during transport. This study aimed to propose optimal IHT for patients with an infectious disease presenting in an out-patient area. Design: The map of a West China Hospital was used. We also used field investigation findings and simulated person flow to establish pathway length and transportation time. We identified three optimum pathways and estimated safety boundary marks, including a patient transportation border (PTB) and safety transportation border (STB). Finally, IHT, PTB, and STP formed a virtual transport pipeline (VTP) and a traceable IHT management system, which can generate a virtual isolation space. Results: The three pathways met efficiency, accessibility, and by-stander flow criteria. No facility characteristic modification was required. Conclusions: Using virtual models to identify pathways through out-patient hospital areas may help reduce the risk of infection spread.
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COVID-19 , Doenças Transmissíveis , Humanos , Transporte de Pacientes/métodos , COVID-19/epidemiologia , Meios de Transporte , Fatores de Risco , Doenças Transmissíveis/epidemiologiaRESUMO
OBJECTIVE: The purpose of this study was to evaluate the rehabilitation effects of four common interventions (BA: body acupuncture, SA: scalp acupuncture, TA: tongue acupuncture, SLT: speech and language training) used singly or in combination with language function in patients with post-stroke aphasia (PSA). DESIGN: We systematically searched PubMed, EMBASE, Cochrane Library, Ovid, Web of Science, CNKI, VIP, and Wanfang from inception to 4 April 2022. Only randomized controlled trials that met the eligibility criteria were included. The risk of bias of studies included was assessed using the RoB-2 tool. The effects of different interventions for PSA patients were analyzed and ranked according to the surface under the cumulative ranking (SUCRA) analysis. RESULTS: A total of 69 RCTs were included, including 5097 total participants. According to the results of the SUCRA curves, TA ranked highest in improving overall efficacy (SUCRA = 86%) and oral expression score (SUCRA = 86%). BA + TA ranked highest in increasing the comprehension score (SUCRA = 74.9%). BA + SA ranked highest in improving aphasia patients' repetition (SUCRA = 89.2%) and denomination scores (SUCRA = 93%). CONCLUSIONS: Results of our network meta-analysis and SUCRA ranking showed that tongue acupuncture, body acupuncture + tongue acupuncture, and body acupuncture + scalp acupuncture seem to offer better advantages than other interventions for improving the language function in PSA patients. Moreover, it is noteworthy that our results are limited to the Chinese population, since all eligible studies are from China. Future well-designed studies with larger sample sizes and more ethnic groups are required to further verify these findings.
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Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Our previous studies have found that Shuangyu Tiaozhi Decoction (SYTZD) could produce an improvement in NAFLD-related indicators, but the underlying mechanism associated with this improvement remains unclear. The study aimed to investigate the potential mechanism of SYTZD against NAFLD through network pharmacology and experimental verification. The components of SYTZD and SYTZD drug containing serum were analyzed using ultra-performance liquid chromatography to quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS). Active components and targets of SYTZD were screened by the traditional Chinese medical systems pharmacology (TCMSP) and encyclopedia of traditional Chinese medicine (ETCM) databases. NAFLD-related targets were collected from the GeneCards and DisGeNET databases. The component-disease targets were mapped to identify the common targets of SYTZD against NAFLD. Protein-protein interaction (PPI) network of the common targets was constructed for selecting the core targets. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the core targets was performed using the database for annotation, visualization, and integrated discovery (DAVID) database. Furthermore, animal and cell models were constructed for validating the predictions of network pharmacology. Lipid accumulation, liver histopathology, insulin resistance, and core gene expression were measured by oil red O staining, hematoxylin and eosin staining, insulin tolerance test, real-time quantitative polymerase chain reaction, and Western blotting, respectively. Two components and 22 targets of SYTZD against NAFLD were identified by UPLC-Q/TOF-MS and relevant databases. PPI analysis found that ESR1, FASN, mTOR, HIF-1α, VEGFA, and GSK-3ß might be the core targets of SYTZD against NAFLD, which were mainly enriched in the thyroid hormone pathway, insulin resistance pathway, HIF-1 pathway, mTOR pathway, and AMPK pathway. Experimental results revealed that SYTZD might exert multiple anti-NAFLD mechanisms, including improvements in lipid deposition, inflammation, and insulin resistance. SYTZD treatment led to decreases in the lipid profiles, hepatic enzyme levels, inflammatory cytokines, and homeostatic model assessment for insulin resistance (HOMA-IR). SYTZD treatment affected relative mRNA and protein levels associated with various pathways. Our findings reveal that SYTZD could alleviate NAFLD through a multi-component, multi-target, and multi-pathway mechanism of action.
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Maximum intensity projection (MIP) is a standard volume-rendering technique for 3D volumetric data processing. For example, given a 3D CT data, it simply projects the voxel values with its maximum intensity on a specific view to output a 2D image. Recently, MIP is further combined with Btrfly Net for vertebrae labelling task. However, this simple reformations of 3D data leads to loss of rich context information in volumetric data. In this paper, we propose a learned orthographic pooling approach instead of image processing based MIP. Typically, a simple conv-simple and bottleneck pooling modules are introduced to learn the orthographic projection of 3D data and output 2D intermediate feature maps. To this end, the learned orthographic pooling helps preserve detail information of 3D context during projection. Furthermore, an unified Btrfly Net is provided for vertebrae labelling by integrating the orthographic pooling sub-network. The novel Btrfly Net with orthographic pooling sub-network is evaluated on the 2014 MICCAI vertebra localization challenge dataset. Compared to original Butfly Net with MIP, orthographic pooling, the learned MIP largely boosts the performance of vertebrae labelling.
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Processamento de Imagem Assistida por Computador , Coluna Vertebral , Processamento de Imagem Assistida por Computador/métodos , Coluna Vertebral/diagnóstico por imagemRESUMO
Non-alcoholic fatty liver disease (NAFLD), a spectrum of liver disorders from non-alcoholic fatty liver (NAFL) to the more severe non-alcoholic steatohepatitis (NASH), is the leading etiology of chronic liver disease and its global prevalence is increasing. Hepatic steatosis, a condition marked by an abnormal buildup of triglycerides in the liver, is the precursor to NAFLD. Differentiated cluster 36 (CD36), a scavenger receptor class B protein, is a membrane receptor that recognizes multiple lipid and non-lipid ligands. It is generally agreed that CD36 contributes significantly to hepatic steatosis by taking part in fatty acid uptake as well as triglyceride storage and secretion. While there has not been any conclusive research on how CD36 inhibitors prevent NAFLD from progressing and no clinically approved CD36 inhibitors are currently available for use in NAFLD, CD36 remains a target worthy of further investigation in NAFLD. In recent years, the potential role of natural products acting through CD36 in treating non-alcoholic fatty liver disease has attracted much attention. This paper offers an overview of the pathogenesis of CD36 in NAFLD and summarizes some of the natural compounds or extracts that are currently being investigated for modulating NAFLD via CD36 or the CD36 pathway, providing an alternative approach to the development of CD36-related drugs in NAFLD.
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Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Cirrose Hepática/metabolismo , Ácidos Graxos/uso terapêuticoRESUMO
Objective To investigate the role of mast cell activation products in promoting angiogenesis. Methods SD rat peritoneal mast cells (RPMC) were isolated and activated by calcium ionophore. The activation products were extracted and the activity of chymase was detected. Thirty BALB/c mice were randomly divided into a control group, an activation product group, and an inhibitor group (10 mice in each group), and the angiogenisis of mast cell activation products was studied by matrigel plug assay. In the matrigel plug, the hemoglobin (Hb) concentration was determined by hemiglobincyanide (HiCN) method, the distribution of blood vessels was observed by HE staining, and the microvessel density (MVD) was detected by CD34 immunohistochemical staining. Results The activity of chymase was detected in the activation products of isolated RPMCs. The results of mice matrigel plug assay showed that the Hb level in matrigel plug of the activation product group was about 7 times higher than that of the control group, while the Hb level of the inhibitor group was 80.8% lower than that of the activation product group. HE staining showed new blood vessels in the matrigel plug of the activation product group, and some vascular lumens were observed. The results of MVD showed that the MVD in matrigel plug of the activation product group was about 5 times than that of the control group, while MVD of the inhibitor group was 66.2% lower than that of the activation product group. Conclusion Chymase, a product of mast cell activation, is the main mediator to promote angiogenesis in mouse matrigel plugs.
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Mastócitos , Animais , Quimases , Colágeno , Combinação de Medicamentos , Laminina , Camundongos , Camundongos Endogâmicos BALB C , Proteoglicanas , Ratos , Ratos Sprague-DawleyRESUMO
Hyperlipidemia is a disorder of lipid metabolism, which is a major cause of coronary heart disease. Although there has been considerable progress in hyperlipidemia treatment, morbidity and risk associated with the condition continue to rise. The first-line treatment for hyperlipidemia, statins, has multiple side effects; therefore, development of safe and effective drugs from natural products to prevent and treat hyperlipidemia is necessary. Diosgenin is primarily derived from fenugreek (Trigonella foenum graecum) seeds, and is also abundant in medicinal herbs such as Dioscorea rhizome, Dioscorea septemloba, and Rhizoma polygonati, is a well-known steroidal sapogenin and the active ingredient in many drugs to treat cardiovascular conditions. There is abundant evidence that diosgenin has potential for application in correcting lipid metabolism disorders. In this review, we evaluated the latest evidence related to diosgenin and hyperlipidemia from clinical and animal studies. Additionally, we elaborate the pharmacological mechanism underlying the activity of diosgenin in treating hyperlipidemia in detail, including its role in inhibition of intestinal absorption of lipids, regulation of cholesterol transport, promotion of cholesterol conversion into bile acid and its excretion, inhibition of endogenous lipid biosynthesis, antioxidation and lipoprotein lipase activity, and regulation of transcription factors related to lipid metabolism. This review provides a deep exploration of the pharmacological mechanisms involved in diosgenin-hyperlipidemia interactions and suggests potential routes for the development of novel drug therapies for hyperlipidemia.
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While color information is known to provide rich discriminative clues for visual inference, most modern visual trackers limit themselves to the grayscale realm. Despite recent efforts to integrate color in tracking, there is a lack of comprehensive understanding of the role color information can play. In this paper, we attack this problem by conducting a systematic study from both the algorithm and benchmark perspectives. On the algorithm side, we comprehensively encode 10 chromatic models into 16 carefully selected state-of-the-art visual trackers. On the benchmark side, we compile a large set of 128 color sequences with ground truth and challenge factor annotations (e.g., occlusion). A thorough evaluation is conducted by running all the color-encoded trackers, together with two recently proposed color trackers. A further validation is conducted on an RGBD tracking benchmark. The results clearly show the benefit of encoding color information for tracking. We also perform detailed analysis on several issues, including the behavior of various combinations between color model and visual tracker, the degree of difficulty of each sequence for tracking, and how different challenge factors affect the tracking performance. We expect the study to provide the guidance, motivation, and benchmark for future work on encoding color in visual tracking.