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1.
J Immunol Res ; 2022: 4126273, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35345778

RESUMO

American ginseng (Panax quinquefolius L.) is an herbal medicine with polysaccharides as its important active ingredient. The purpose of this research was to identify the effects of the polysaccharides of P. quinquefolius (WQP) on rats with antibiotic-associated diarrhoea (AAD) induced by lincomycin hydrochloride. WQP was primarily composed of galacturonic acid, glucose, galactose, and arabinose. The yield, total sugar content, uronic acid content, and protein content were 6.71%, 85.2%, 31.9%, and 2.1%, respectively. WQP reduced the infiltration of inflammatory cells into the ileum and colon, reduced the IL-1ß, IL-6, IL-17A, and TNF-α levels, increased the levels of IL-4 and IL-10 in colon tissues, improved the production of acetate and propionate, regulated the gut microbiota diversity and composition, improved the relative richness of Lactobacillus and Bacteroides, and reduced the relative richness of Blautia and Coprococcus. The results indicated that WQP can enhance the recovery of the intestinal structure in rats, reduce inflammatory cytokine levels, improve short-chain fatty acid (SCFA) levels, promote recovery of the gut microbiota and intestinal mucosal barrier, and alleviate antibiotic-related side effects such as diarrhoea and microbiota dysbiosis caused by lincomycin hydrochloride. We found that WQP can protect the intestinal barrier by increasing Occludin and Claudin-1 expression. In addition, WQP inhibited the MAPK inflammatory signaling pathway to improve the inflammatory status. This study provides a foundation for the treatment of natural polysaccharides to reduce antibiotic-related side effects.


Assuntos
Panax , Animais , Antibacterianos/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Diarreia/metabolismo , Lincomicina/farmacologia , Lincomicina/uso terapêutico , Sistema de Sinalização das MAP Quinases , Panax/química , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Ratos
2.
J Agric Food Chem ; 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35536225

RESUMO

Dysregulated hepatic lipogenesis represents a promising druggable target for treating nonalcoholic steatohepatitis (NASH). This work aims to evaluate the therapeutic efficacy of caffeine in a NASH mouse model displaying increased hepatic lipogenesis driven by constitutive hepatic overexpression of the active v-akt murine thymoma viral oncogene homolog (AKT). Caffeine was administered in the AKT mice to study the efficacy in vivo. AKT-transfected and insulin-stimulated human hepatoma cells were used for in vitro experiments. The results demonstrated that caffeine ameliorated hepatic steatosis and inflammatory injury in vivo. Mechanistically, caffeine repressed the AKT/mTORC1 and SREBP-1/ACC/FASN signaling in mice and in vitro. Furthermore, caffeine impaired NF-κB activation by stabilizing IκBα, resulting in a reduction of proinflammatory mediators interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). Notably, caffeine abolished mTORC1/FASN-dependent MyD88 palmitoylation, which could be essential for its anti-inflammatory potential. Collectively, these results suggest that caffeine consumption could be advantageous in the prevention and therapy of NASH, especially in the subset accompanied by increased de novo lipogenesis.

3.
Natl Sci Rev ; 9(5): nwab210, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35547957

RESUMO

Tracing the closure of oceans with irregular margins and the formation of an orocline are crucial for understanding plate reconstruction and continental assembly. The eastern Central Asian Orogenic Belt, where the Mongol-Okhotsk orocline is situated, is one of the world's largest magmatic provinces. Using a large data set of U-Pb zircon ages, we updated the timing of many published igneous rocks, which allowed us to recognize tightly 'folded' linear Carboniferous-Jurassic magmatic belts that wrap around the Mongol-Okhotsk suture and their migrations both sutureward and suture-parallel. The new successive magmatic belts reveal a rollback, scissor-like (or zipper-like) closure of the Mongol-Okhotsk Ocean that was fundamentally controlled by coeval subduction rollback and rotation of the Siberian and Mongolian-Erguna blocks. This study also demonstrates the complex mechanisms and processes of the closure of an ocean with irregular margins and the formation of a consequent orocline.

4.
Sci Total Environ ; : 155886, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35569652

RESUMO

An accurate estimation of thaw depth is critical to understanding permafrost changes due to climate warming on the Qinghai-Tibetan Plateau (QTP). However, previous studies mainly focused on the interannual changes of active layer thickness (ALT) across the QTP, and little is known about the changes in the seasonal thaw depth. Machine learning (ML) is a critical tool to accurately estimate the ALT of permafrost, but a direct comparison of ML with deep learning (DL) in ALT projection regarding the model performance is still lacking. Here, ML, namely random forest (RF), and DL algorithms like convolutional neural networks (CNN) and long short-term memory (LSTM) neural networks were compared to estimate the interannual changes of ALT and seasonal thaw depth on the QTP. Meteorological series, in-situ collected ALT observations, and geospatial information were used as predictors. The results show that both ML and DL methods are capable of estimating ALT and seasonal thaw depth in permafrost areas. The CNN and LSTM models developed using longer lagging times exhibit better performance in thaw depth prediction while the RF models are either mediocre or sometimes even worse as the lagging time increases. The results show that the ALT from 2003 to 2011 on the QTP exhibits an increasing trend, especially in the northern region. In addition, 68.8%, 88.7%, 52.5%, and 47.5% of the permafrost regions on the QTP have deepened seasonal thaw depth in spring, summer, autumn, and winter, respectively. The correlation between air temperature and permafrost thaw depth ranges from 0.65 to 1 with the time lag ranging from 1 to 32 days. This study shows that ML and DL can be effectively used in retrieving ALT and seasonal thaw depth of permafrost, and could present an efficient way to figure out the interannual and seasonal variations of permafrost conditions under climate warming.

5.
Ying Yong Sheng Tai Xue Bao ; 33(4): 1131-1136, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35543069

RESUMO

Bisphenol A (BPA) is a synthetic estrogen compound, which widely exists in the environment, interferes with mammalian endocrine and affects the function of reproductive system of males. Taking fresh sperm of boar, 17 ℃ preservation boar sperm, and mouse sperm as test materials, we examined the effects of BPA (0, 0.1,1,10,100 µmol∙L-1) on proteins tyrosine phosphorylation in sperm and the molecular mechanism by using wes-tern blot (WB) and immunofluorescence techniques coupled to in vitro culture method. The results showed that low BPA concentration (0.1, 1 µmol∙L-1) markedly accelerated the protein tyrosine phosphorylation of fresh boar capacitated sperm. However, the tyrosine phosphorylation of boar sperm decreased in high BPA concentration (10, 100 µmol∙L-1). The tyrosine phosphorylation of the mouse sperm raised with the increases of BPA concentration. Moreover, BPA affected different kinds of proteins related to tyrosine phosphorylation modification of porcine and mouse sperm capacitation, suggesting that the effect of BPA exposure on mammalian sperm was species-specific. Furthermore, the results of immunofluorescence showed that the effects of BPA on protein tyrosine phosphorylation in sperm mainly occurred in the middle and principal piece of flagellum.


Assuntos
Capacitação Espermática , Espermatozoides , Animais , Compostos Benzidrílicos , Masculino , Mamíferos/metabolismo , Camundongos , Fenóis , Fosforilação , Proteínas , Suínos , Tirosina
6.
J Hosp Palliat Nurs ; 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35560146

RESUMO

The objective of this study was to explore factors influencing Taiwanese older adults' end-of-life (EOL) care preferences. A cross-sectional questionnaire survey was conducted in 2 geriatric wards of a veterans' hospital. Fifty-five older adults aged 65 years or older were included. Structured questionnaires were used to collect data regarding demographic characteristics, EOL care preferences, stages of change for advance care planning behaviors, and reluctance to burden others. The study revealed that nearly 60% of the participants preferred to let their spouses, adult children, or health care professionals make the decisions. Furthermore, 83.6% of the participants lived with their family members and were moderately to severely disabled with a certain degree of dependence on their family members. Sex, independence, discussion of advance care planning with family members, and completion of advance directives were significantly correlated with EOL care preferences. The regression model showed that the participants' discussion of advance care planning with their family members influenced their EOL care preferences. The results demonstrate that family is an essential consideration for older adults choosing EOL care. Accordingly, because Chinese culture focuses on family harmony, improving communication between older adults and their family members is crucial for promoting advance care planning.

7.
Environ Res ; : 113376, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35561827

RESUMO

Microbes (e.g., bacteria and archaea) are indispensable components for the key biological processes of estuarine ecosystems and three main habitats (sediment, particle, and water) are harboring diverse estuarine microbes. However, we still know little about how the microbial community structures, potential keystone species, and network properties change among these three habitats in estuarine ecosystems. In this study, we collected size-fractioned water and sediment samples from the Pearl River Estuary to reveal their microbial diversity, community structures, network properties, and potential keystone taxa. We found that the sediment microbial community was remarkably more diverse than particle-attached (PA) and free-living (FL) communities, whereas its ecological network was less complex in terms of node distance and connectivity. TOC was determined as the main driver of sediment community, while the PA and FL communities were predominantly shaped by NO2-, non-ionic ammonia (NH) and pH. Among the bulk water, there were no significant differences between PA and FL communities in diversity, community structure, and network complexity. However, the PA community was more susceptible to metal elements, suggesting their higher level of involvement in physiological metabolism. Potential keystone taxa among community networks were taxonomically divergent in three habitats. Specifically, Synechococcales (Cyanobacteria) and Actinomarinales (Actinobacteria) exclusively served as the module-hubs in FL network, while members from phylum Proteobacteria and Bacteroidetes were the module-hubs and connectors in PA network. Potential keystone taxa in sediment network were more diverse and covered 9 phyla, including the only archaeal lineage Bathyarchaeia (Crenarchaeota). Overall, our study provided more detailed information about estuarine microbial communities in three habitats, especially the potential keystone species, which provided new perspectives on evaluating further effects of anthropogenic disturbances on estuarine microbes and facilitated the environment monitoring based on microbial community.

8.
J Neuroinflammation ; 19(1): 106, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35513834

RESUMO

BACKGROUND: This study investigated the relationships of neutrophil count (NC), neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) with cerebral small vessel disease (CSVD). METHODS: A total of 3052 community-dwelling residents from the Poly-vasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study were involved in this cross-sectional study. CSVD burden and imaging markers, including white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces in basal ganglia (BG-EPVS), were assessed according to total CSVD burden score. The associations of NC, NLR and SII with CSVD and imaging markers were evaluated using logistic regression models. Furthermore, two-sample Mendelian randomization (MR) analysis was performed to investigate the genetically predicted effect of NC on CSVD. The prognostic performances of NC, NLR and SII for the presence of CSVD were assessed. RESULTS: At baseline, the mean age was 61.2 ± 6.7 years, and 53.5% of the participants were female. Higher NC was suggestively associated with increased total CSVD burden and modified total CSVD burden (Q4 vs. Q1: common odds ratio (cOR) 1.33, 95% CI 1.05-1.70; cOR 1.28, 95% CI 1.02-1.60) and marginally correlated with the presence of CSVD (OR 1.29, 95% CI 1.00-1.66). Furthermore, elevated NC was linked to a higher risk of lacune (OR 2.13, 95% CI 1.25-3.62) and moderate-to-severe BG-EPVS (OR 1.67, 95% CI 1.14-2.44). A greater NLR was related to moderate-to-severe BG-EPVS (OR 1.68, 95% CI 1.16-2.45). Individuals with a higher SII had an increased risk of modified WMH burden (OR 1.35, 95% CI 1.08-1.69) and moderate-to-severe BG-EPVS (OR 1.70, 95% CI 1.20-2.41). MR analysis showed that genetically predicted higher NC was associated with an increased risk of lacunar stroke (OR 1.20, 95% CI 1.04-1.39) and small vessel stroke (OR 1.21, 95% CI 1.06-1.38). The addition of NC to the basic model with traditional risk factors improved the predictive ability for the presence of CSVD, as validated by the net reclassification index and integrated discrimination index (all p < 0.05). CONCLUSIONS: This community-based population study found a suggestive association between NC and CSVD, especially for BG-EPVS and lacune, and provided evidence supporting the prognostic significance of NC.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Disfunção Cognitiva , Acidente Vascular Cerebral , Idoso , Biomarcadores , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/genética , Disfunção Cognitiva/complicações , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações
10.
J Biomech ; 138: 111132, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35569428

RESUMO

A repetitive sit-to-stand (STS) task is often used as a fatiguing protocol. Although post-fatigue reductions in muscle strength have been frequently used to indicate fatigue, little is known about changes in body movement during the fatiguing process. This study examined changes in variability of hip-knee and knee-ankle coordination during the STS fatiguing course in 15 young (age: 26.7 ± 5.8 years; 9 females, 6 males) and 15 older adults (age: 69.3 ± 5.7 years; 9 females, 6 males). Participants were asked to perform repetitive STS movements until exhaustion or for 30 min at a self-selected pace. Motion data from 3 consecutive STS cycles were extracted from every minute during the entire fatiguing course and time normalized to STS duration and dummy coded as five stages: 0-20, 20-40, 40-60, 60-80, and 80-100% of the course. Outcome variables were hip-knee and knee-ankle inter-joint coordination variabilities. A 2*5 mixed-effect ANOVA was used to examine changes in variability during different stages of the course in young and older adults. No Age × Time interactions were found in either hip-knee or knee-ankle coordination variability. The hip-knee coordinative variability significantly increased along the STS fatiguing course regardless of age, and the knee-ankle variability from standing to sitting was also higher at the ending, when compared to the beginning, of the fatiguing protocol. The impact of fatigue during repetitive STS protocol is not only limited to a force production decline but also manifested as increased coordinative variability, which could be considered as a fatigue indicator.

11.
Rheumatol Ther ; 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35579829

RESUMO

INTRODUCTION: Psoriatic arthritis (PsA) is a common inflammatory disease affecting the peripheral and axial skeleton. History of psoriasis (PSO), either personal or family history, is an important factor in the diagnosis of PsA. We investigated the association between history of PSO and clinical characteristics of PsA. METHODS: PsA patients were consecutive recruited from 2019 to 2020. These patients were subjected to clinical, biochemical, and radiographic examinations, and disease activity was evaluated. Continuous and categorical variables analyses were presented. RESULTS: All registered patients (296 cases) met the classification criteria of PsA. They were divided into three groups based on the history of psoriasis (PSO), as: (1) 145 patients with PSO themselves (pPsA); (2) 96 patients with family history of PSO (fPsA); (3) 55 patients with family history and coexisting PSO themselves (fPsA/PSO). Compared to fPsA/PSO, the levels of CRP, ESR, uric acid, DAPSA, BASDAI, ASDAS, and BASFI were lower in fPsA, but similar to pPsA. The severity of sacroiliitis tended to be more severe in fPsA/PSO than fPsA (OR2 vs. 3 0.508; 95% CI 0.272 to 0.949, p < 0.05). No significant differences were found in HLA-B-27 and common inflammatory articular and extra-articular manifestations among the three groups. Furthermore, there were no differences in LEI, TJC, SJC, and DAS28CRP. Interestingly, a correlation was found between the ages of individuals with PSO and the onset of arthritis, and the earliest arthritis onset occurred in fPsA/PSO patients (p < 0.001). CONCLUSIONS: Our study demonstrates that currently existing cutaneous lesions in patients themselves are correlated with disease activity and severity of axial joint damage, whereas family history does not have an evident impact on the disease activity of PsA.

12.
Leg Med (Tokyo) ; 58: 102086, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35567843

RESUMO

The overall number of drug abuse cases has been on the rise around the world, causing it a disaster in many countries. In this retrospective study, we analyzed the characteristics of 11,903 drug abuse cases in Beijing, the capital of China, in the perspective of age, gender, nationality, region, season, type of specimens and various drugs, respectively. The case information was collected by the national-level forensic toxicology laboratory, which belongs to the China University of Political Science and Law. It was shown that the overall number of drug abuse cases had increased sharply from 2018 to 2019 and had a decrease of 25% in 2020. The incidence of drug abuse cases involving men was much higher than that of the cases involving women. The adolescents and young adults accounted for the largest share of drug abusers in our study. Haidian, as a national center of scientific and technological innovation with global influence, had the largest percentage of toxic substance-related cases, and the change was more pronounced than other districts during the 3-year-period. Chaoyang was second to Haidian in the number toxic substance-related cases. As a key window of economic, Chaoyang had the highest number of foreigner drug cases. June to August had the highest number of drug abuse cases, while amphetamines, opioids, cannabis and cocaine were the most common toxic substances involved in the cases we detected. To our knowledge, this is the first study to provide an overall analysis of drug abuse cases in Beijing, China. The study indicated the presence of a wide number of drug abuse cases in the capital city and confirmed the threat for the public safety and health. Such forensic information can assist the government to devise intelligence-based preventive and repressive measures and policies.

13.
Nat Commun ; 13(1): 2443, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508459

RESUMO

The metal-support interfaces between metals and oxide supports have long been studied in catalytic applications, thanks to their significance in structural stability and efficient catalytic activity. The metal-rare earth oxide interface is particularly interesting because these early transition cations have high electrophilicity, and therefore good binding strength with Lewis basic molecules, such as H2O. Based on this feature, here we design a highly efficient composite Ni-Y2O3 catalyst, which forms abundant active Ni-NiOx-Y2O3 interfaces under the water-gas shift (WGS) reaction condition, achieving 140.6 µmolCO gcat-1 s-1 rate at 300 °C, which is the highest activity for Ni-based catalysts. A combination of theory and ex/in situ experimental study suggests that Y2O3 helps H2O dissociation at the Ni-NiOx-Y2O3 interfaces, promoting this rate limiting step in the WGS reaction. Construction of such new interfacial structure for molecules activation holds great promise in many catalytic systems.

14.
Microbiol Spectr ; : e0013422, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35475656

RESUMO

Increasing biodiversity loss profoundly affects community structure and ecosystem functioning. However, the differences in community assembly and potential drivers of the co-occurrence network structure of soil fungi and bacteria in association with tree species richness gradients are poorly documented. Here, we examined soil fungal and bacterial communities in a Chinese subtropical tree species richness experiment (from 1 to 16 species) using amplicon sequencing targeting the internal transcribed spacer 2 and V4 hypervariable region of the rRNA genes, respectively. Tree species richness had no significant effect on the diversity of either fungi or bacteria. In addition to soil and spatial distance, tree species richness and composition had a significant effect on fungal community composition but not on bacterial community composition. In fungal rather than bacterial co-occurrence networks, the average degree, degree centralization, and clustering coefficient significantly decreased, but the modularity significantly increased with increasing tree species richness. Fungal co-occurrence network structure was influenced by tree species richness and community composition as well as the soil carbon: nitrogen ratio, but the bacterial co-occurrence network structure was affected by soil pH and spatial distance. This study demonstrates that the community assembly and potential drivers of the co-occurrence network structure of soil fungi and bacteria differ in the subtropical forest. IMPORTANCE Increasing biodiversity loss profoundly affects community structure and ecosystem functioning. Therefore, revealing the mechanisms associated with community assembly and co-occurrence network structure of microbes along plant species diversity gradients is very important for understanding biodiversity maintenance and community stability in response to plant diversity loss. Here, we compared the differences in community assembly and potential drivers of the co-occurrence network structure of soil fungi and bacteria in a subtropical tree diversity experiment. In addition to soil and spatial distance, plants are more strongly predictive of the community and co-occurrence network structure of fungi than those of bacteria. The study highlighted that plants play more important roles in shaping community assembly and interactions of fungi than of bacteria in the subtropical tree diversity experiment.

15.
Am J Chin Med ; : 1-28, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35475976

RESUMO

Electroacupuncture (EA) is commonly used to treat cerebrovascular diseases. This study aimed to clarify the mechanisms of action of treatments of cerebral ischemic stroke from the perspective of gut microecology. We used a mouse model and cell cultures to investigate the effects of EA on the intestinal microflora in mice models of middle cerebral artery occlusion (MCAO) and the mechanisms underlying the antioxidant activities of metabolites. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota. Metabolomic analysis was performed to characterize the metabolic profile differences between the mice in the EA + MCAO and MCAO groups. Gavaging with feces relieved brain damage in mice that received EA (EA mice) more than in mice that did not (non-EA [NEA] mice). The gut microbial composition and metabolic profiles of the EA and NEA mice were different. In particular, the microbiota from the mice in the EA or EA-FMT groups generated more indole-3-propionic acid (IPA) than the microbiota from the mice in the MCAO or NEA-FMT groups. We confirmed that IPA binds to specific melatonin receptors (MTRs) in target cells and exerts antioxidant effects by adding MTR inhibitors or knocking out the MTR1 gene in vivo and in the oxygen and glucose deprivation/reperfusion models of N2a cell experiments. EA can prevent ischemic stroke by improving the composition of intestinal microbiota in MCAO mice. Moreover, this study reveals a new mechanism of intestinal flora regulation of stroke that differs from inflammation/immunity, namely gut microbiota regulates stroke by affecting IPA levels.

16.
ChemMedChem ; : e202200030, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35451199

RESUMO

Human p97 is a potential drug target in oncology. Mutation-driven drug resistance is an obstacle to the long-term efficacy of targeted therapy. We found that the ATPase activity for one of the CB-5083-resistant p97 mutants was reduced, which also attenuated the degradation of K48 ubiquitinated proteins in cells. To understand how p97 mutant cells with significantly reduced ATPase activity can still grow, we discovered reduced levels of CHOP and NF-κB activation in the p97 mutant cells and these cellular changes can potentially protect HCT116 cells from death due to lowered p97 activity. In addition, the NF-kB inhibitor Sulforaphane reduces proliferation of CB-5083 resistant cells and acts synergistically with CB-5083 to block proliferation of the parental HCT116 cells. The combination of Sulforaphane and CB-5083 may be a useful treatment strategy to combat CB-5083 resistance.

17.
Metabolism ; 131: 155200, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35405150

RESUMO

BACKGROUND: Schisandrin B (Sch B), which inhibits hepatic steatosis caused by non-alcoholic fatty liver disease (NAFLD), is one of the most active dibenzocyclooctadienes isolated from Schisandra chinensis (Turcz.) Baill with various pharmacological activities. In this study, the role of Sch B-induced autophagy in lipid-lowering activities of Sch B was examined and the underlying mechanisms were elucidated. METHODS: Free fatty acid (FFA)-stimulated HepG2 cells and mouse primary hepatocytes (MPHs) and high-fat diet (HFD)-fed mice were used as NAFLD models. The role of Sch B-induced autophagy in lipid-lowering effects of Sch B was assessed using ATG5/TFEB-deficient cells and 3-methyladenine (3-MA)-treated hepatocytes and mice. RESULTS: Sch B simultaneously active autophagy through AMPK/mTOR pathway and decreased the number of lipid droplets in FFA-treated HepG2 cells and MPHs. Additionally, siATG5/siTFEB transfection or 3-MA treatment mitigated Sch B-induced autophagy and activation of fatty acid oxidation (FAO) and ketogenesis in FFA-treated HepG2 cells and MPHs. Sch B markedly decreased hepatic lipid content and activated the autophagy through AMPK/mTOR pathway in HFD-fed mice. However, the activities of Sch B were suppressed upon 3-MA treatment. Sch B upregulated the expression of key enzymes involved in FAO and ketogenesis, which was mitigated upon 3-MA treatment. Moreover, changes in hepatic lipid components and amino acids may be related to the Sch B-induced autophagy pathway. CONCLUSION: These results suggested that Sch B inhibited hepatic steatosis and promoted FAO by activation of autophagy through AMPK/mTOR pathway. Our study provides novel insights into the hepatic lipophagic activity of Sch B and its potential application in the management of NAFLD.


Assuntos
Proteínas Quinases Ativadas por AMP , Hepatopatia Gordurosa não Alcoólica , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Autofagia , Ciclo-Octanos , Dieta Hiperlipídica , Ácidos Graxos não Esterificados/metabolismo , Hepatócitos/metabolismo , Corpos Cetônicos/metabolismo , Lignanas , Metabolismo dos Lipídeos , Fígado/metabolismo , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Compostos Policíclicos , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
18.
BMC Pulm Med ; 22(1): 156, 2022 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-35462545

RESUMO

BACKGROUND: China launched its new round of health care reform to develop primary care in 2009, establishing 954,390 primary care institutions that employed over 10 million staff by 2019. However, some studies have shown that the prevention and management of respiratory diseases is inadequate in these institutions. METHODS: We conducted a cross-sectional survey of grassroots institutions throughout China between September and December 2020 based on the standardized Prevention and Treatment System and Capacity Building Project of Respiratory Diseases in primary care settings. The operation of the respiratory department in primary health care institutions was evaluated in terms of facilities, drugs, personnel and management of chronic diseases by means of questionnaires. Descriptive analyses were performed to calculate percentages and frequencies of key parameters. RESULTS: A total of 144 primary health care institutions were surveyed, including 51 in the east, 82 in the west, 9 in the central and 2 in the northeast. Approximately 60% of institutions had spirometers and pulse oximeters. The majority had short-acting bronchodilators, theophylline, systemic corticosteroids, antibiotics, and traditional Chinese medicine. More than half had at least one respiratory physician and operator for spirometry. Half of the institutions carried out screening of chronic obstructive pulmonary disease within the jurisdiction. The institutions in the east were superior to those in the west regarding the equipment, common drugs, medical staff, and management of respiratory diseases. CONCLUSIONS: The study reveals that the overall operation of the respiratory department in primary care settings needs to be further strengthened. It is crucial to provide adequate essential equipment, medical professionals, and medicines for proper diagnosis and treatment of chronic respiratory diseases, as well as improving the management of diseases.


Assuntos
Transtornos Respiratórios , China/epidemiologia , Doença Crônica , Estudos Transversais , Humanos , Atenção Primária à Saúde , Transtornos Respiratórios/prevenção & controle
19.
Cell Death Discov ; 8(1): 187, 2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35397620

RESUMO

Previous studies have demonstrated that cardiomyocyte apoptosis, ferroptosis, and inflammation participate in the progress of sepsis-induced cardiomyopathy (SIC). Although Islet cell autoantigen 69 (ICA69) is an imperative molecule that could regulate inflammation and immune response in numerous illnesses, its function in cardiovascular disease, particularly in SIC, is still elusive. We confirmed that LPS significantly enhanced the expression of ICA69 in wild-type (WT) mice, macrophages, and cardiomyocytes. The knockout of ICA69 in lipopolysaccharide(LPS)-induced mice markedly elevated survival ratio and heart function, while inhibiting cardiac muscle and serum inflammatory cytokines, reactive oxygen (ROS), and ferroptosis biomarkers. Mechanistically, increased expression of ICA69 triggered the production of STING, which further resulted in the production of intracellular lipid peroxidation, eventually triggering ferroptosis and heart injury. Intriguingly, ICA69 deficiency only reversed the ferroptotic marker levels, such as prostaglandin endoperoxide synthase 2 (PTGS2), malonaldehyde (MDA), 4-hydroxynonenal (4HNE), glutathione peroxidase 4 (GPX4), superoxide dismutase (SOD), iron and lipid ROS, but had no effects on the xCT-dependent manner. Additionally, greater ICA69 level was identified in septic patients peripheralblood mononuclear cells (PBMCs) than in normal control groups. Generally, we unveil that ICA69 deficiency can relieve inflammation and ferroptosis in LPS-induced murine hearts and macrophages, making targeting ICA69 in heart a potentially promising treatment method for SIC.

20.
Pharmaceutics ; 14(4)2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35456598

RESUMO

Adenosine triphosphate (ATP)-competitive p97 inhibitor CB-5339, the successor of CB-5083, is being evaluated in Phase 1 clinical trials for anti-cancer therapy. Different modes-of-action p97 inhibitors such as allosteric inhibitors are useful to overcome drug-induced resistance, one of the major problems of targeted therapy. We previously demonstrated that allosteric p97 inhibitor NMS-873 can overcome CB-5083-induced resistance in HCT116. Here we employed chemical proteomics and drug-induced thermal proteome changes to identify drug targets, in combination with drug-resistant cell lines to dissect on- and off-target effects. We found that NMS-873 but not CB-5083 affected glycometabolism. By establishing NMS-873-resistant HCT116 cell lines and performing both cell-based and proteomic analysis, we confirmed that NMS-873 dysregulates glycometabolism in a p97-independent manner. We then used proteome integral solubility alteration with a temperature-based method (PISA T) to identify NDUFAF5 as one of the potential targets of NMS-873 in the mitochondrial complex I. We also demonstrated that glycolysis inhibitor 2-DG enhanced the anti-proliferative effect of NMS-873. The polypharmacology of NMS-873 can be advantageous for anti-cancer therapy for colon cancer.

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