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1.
Pak J Pharm Sci ; 36(4): 1079-1084, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37599481

RESUMO

Excessive inflammation caused by sepsis can disrupt gut mucosal barrier and aggravate sepsis. The purpose of the study was to confirm whether citrulline can protect the intestinal mucosal barrier during sepsis. Citrulline was used to pretreat the sepsis mouse model and then endotoxin levels, intestinal mucosal permeability, intestinal mucosal morphology and tight junction protein expression were detected to analyze the effect of citrulline on the gut barrier during sepsis. Statistics revealed that, the amount of endotoxin and intestinal mucosal penetration and the morphological score of the intestinal mucosa of septic mice with citrulline treatment were significantly decreased (P<0.05), while the claudin-1 and occludin protein expression levels were obviously increased in septic mice with citrulline treatment (P<0.05). This study defined the protective effect of citrulline on the intestinal mucosal barrier of septic mice. Future studies should examine whether it has the same effect on patients with sepsis.


Assuntos
Citrulina , Sepse , Animais , Camundongos , Citrulina/farmacologia , Mucosa Intestinal , Sepse/tratamento farmacológico , Modelos Animais de Doenças , Endotoxinas
2.
J Med Virol ; 94(10): 5051-5055, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35729074

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused by the coronavirus severe acute respiratory syndrome coronavirus 2 remains risky worldwide. We elucidate here that good IDM (isolation, disinfection, and maintenance of health) is powerful to reduce COVID-19 deaths based on the striking differences in COVID-19 case fatality rates among various scenarios. IDM means keeping COVID-19 cases away from each other and from other people, disinfecting their living environments, and maintaining their health through good nutrition, rest, and treatment of symptoms and pre-existing diseases (not through specific antiviral therapy). Good IDM could reduce COVID-19 deaths by more than 85% in 2020 and more than 99% in 2022. This is consistent with the fact that good IDM can minimize co-infections and maintain body functions and the fact that COVID-19 has become less pathogenic (this fact was supported with three novel data in this report). Although IDM has been frequently implemented worldwide to some degree, IDM has not been highlighted sufficiently. Good IDM is relative, nonspecific, flexible, and feasible in many countries, and can reduce deaths of some other relatively mild infectious diseases. IDM, vaccines, and antivirals aid each other to reduce COVID-19 deaths. The IDM concept and strategy can aid people to improve their health behavior and fight against COVID-19 and future pandemics worldwide.


Assuntos
Tratamento Farmacológico da COVID-19 , Antivirais/uso terapêutico , Humanos , Pandemias/prevenção & controle , SARS-CoV-2
3.
J Med Virol ; 94(6): 2388-2401, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35072274

RESUMO

The newly established virus family Phenuiviridae in Bunyavirales harbors viruses infecting three kingdoms of host organisms (animals, plants, and fungi), which is rare in known virus families. Many phenuiviruses are arboviruses and replicate in two distinct hosts (e.g., insects and humans or rice). Multiple phenuivirid species, such as Dabie bandavirus, Rift Valley fever phlebovirus, and Rice stripe tenuivirus, are highly pathogenic to humans, animals, or plants. They impose heavy global burdens on human health, livestock industry, and agriculture and are research hotspots. In recent years the taxonomy of Phenuiviridae has been expanded greatly, and research on phenuiviruses has made significant progress. With these advances, this review drew a novel panorama regarding the biomedical significance, distribution, morphology, genomics, taxonomy, evolution, replication, transmission, pathogenesis, and control of phenuiviruses, to aid researchers in various fields to recognize this highly adaptive and important virus family and conduct relevant risk analysis.


Assuntos
Arbovírus , Phlebovirus , Vírus de RNA , Animais , Genômica , Humanos
4.
Liver Int ; 42(9): 1969-1980, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34619026

RESUMO

BACKGROUND: Despite substantial attention paid to the epidemic of nonalcoholic fatty liver disease (NAFLD) in adults, data on the burden and sexual dimorphism of NAFLD in Asian children have not yet been synthesized. METHODS: We conducted a literature search of 735 references up to April 2021. Pooled analyses, stratified analyses and meta-regression were all performed. RESULTS: Thirty-three study populations were finally included. Nine of them comprising 20 595 children showed an overall NAFLD prevalence of 5.53% (95% CI 3.46%-8.72%), in which, 36.64% (95% CI, 27.99%-46.26%) NAFLD subjects had elevated levels of ALT. The prevalence rate of NAFLD increased about 1.6-fold from 2004 to 2010 to the last decade. Male predominant trends were observed in paediatric NAFLD (boys: 8.18%, 95% CI 4.93%-13.26%; girls: 3.60%, 95% CI 1.60%-7.87%). Moreover, meta-analysis showed that after 10 years of age, boys were more prone to have NAFLD than girls (OR = 1.75; P = .0012). In addition, the pooled prevalence of NAFLD increased sequentially in normal-weight (1.49%, 95% CI 0.88%-2.51%, n = 2610), overweight (16.72%, 95% CI 7.07%-34.65%, n = 1265) and obese children (50.13%, 95% CI 41.99%-58.27%, n = 6434 individuals). After full covariate adjustment, the multivariate meta-regression also showed that boy percentage (P = .0396) and body mass index (P < .0001) were positively correlated with prevalent NAFLD. CONCLUSIONS: In Asia, paediatric NAFLD is becoming prevalent over the recent decades, particularly among obese children and boys after 10 years old. The hormonal and chromosomal origins of paediatric NAFLD dimorphism need further investigation.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Obesidade Infantil , Adulto , Índice de Massa Corporal , Criança , Feminino , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Sobrepeso , Obesidade Infantil/epidemiologia , Prevalência , Caracteres Sexuais
5.
Hepatobiliary Pancreat Dis Int ; 21(2): 154-161, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35153138

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) was recently proposed to be renamed metabolic dysfunction-associated fatty liver disease (MAFLD) with the diagnostic criteria revised. We investigated the similarities and differences in the prevalence and clinical characteristics of MAFLD and NAFLD in Chinese adults. METHODS: A cross-sectional study of 9980 Chinese individuals aged 40 years or older was performed between 2011 and 2012 using randomized, stratified cluster sampling in Shanghai, China. A detailed questionnaire and the results of abdominal ultrasonography, a standardized 2-h 75-g oral glucose tolerance test and blood biochemical examinations were collected. RESULTS: A total of 9927 subjects were included in this study. The prevalence of MAFLD (40.3%) was significantly higher than that of NAFLD (36.9%) (P < 0.05). MAFLD was highly prevalent in type 2 diabetes mellitus (T2DM) (53.8%), impaired fasting glucose (35.7%) and impaired glucose tolerance (40.9%). High risk of advanced fibrosis based on fibrosis-4 was highly prevalent (14.7%) in lean MAFLD with T2DM. Among 9927 subjects, 3481 (35.1%) fulfilled the diagnostic criteria for MAFLD and NAFLD (MAFLD+NAFLD+), 521 (5.2%) MAFLD+NAFLD-, and 181 (1.8%) MAFLD-NAFLD+. The MAFLD+NAFLD- group had more significant metabolic disorders than those in the MAFLD+NAFLD+ group (all P < 0.05). Among MAFLD-NAFLD+ subjects, 82.9% had metabolic disorders. CONCLUSIONS: The new definition of MAFLD may better reflect the pathogenesis related to metabolism. Future research should focus on studying the natural history, pathogenesis and treatment effectivity of the overlap and non-overlap of NAFLD and MAFLD subjects.


Assuntos
Diabetes Mellitus Tipo 2 , Doenças Metabólicas , Hepatopatia Gordurosa não Alcoólica , Adulto , China/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Fibrose , Humanos , Doenças Metabólicas/complicações , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prevalência
6.
Hepatology ; 72(2): 454-469, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31782176

RESUMO

BACKGROUND AND AIMS: Hepatic macrophages can be activated by many factors such as gut-derived bacterial components and factors released from damaged hepatocytes. Macrophage polarization toward a proinflammatory phenotype (M1) represents an important event in the disease progression of nonalcoholic fatty liver disease (NAFLD). However, the underlying molecular mechanisms remain incompletely understood. Exosomes have been identified as important mediators for cell-cell communication by transferring various biological components such as microRNAs (miRs), proteins, and lipids. The role of exosomes in crosstalk between hepatocytes and macrophages in disease progression of NAFLD is yet to be explored. APPROACH AND RESULTS: In the present study, we reported that lipotoxic injury-induced release of hepatocyte exosomes enriched with miR-192-5p played a critical role in the activation of M1 macrophages and hepatic inflammation. Serum miR-192-5p levels in patients with NAFLD positively correlated with hepatic inflammatory activity score and disease progression. Similarly, the serum miR-192-5p level and the number of M1 macrophages, as well as the expression levels of the hepatic proinflammatory mediators, were correlated with disease progression in high-fat high-cholesterol diet-fed rat models. Lipotoxic hepatocytes released more miR-192-5p-enriched exosomes than controls, which induced M1 macrophage (cluster of differentiation 11b-positive [CD11b+ ]/CD86+ ) activation and increase of inducible nitric oxide synthase, interleukin 6, and tumor necrosis factor alpha expression. Furthermore, hepatocyte-derived exosomal miR-192-5p inhibited the protein expression of the rapamycin-insensitive companion of mammalian target of rapamycin (Rictor), which further inhibited the phosphorylation levels of Akt and forkhead box transcription factor O1 (FoxO1) and resulted in activation of FoxO1 and subsequent induction of the inflammatory response. CONCLUSIONS: Hepatocyte-derived exosomal miR-192-5p plays a critical role in the activation of proinflammatory macrophages and disease progression of NAFLD through modulating Rictor/Akt/FoxO1 signaling. Serum exosomal miR-192-5p represents a potential noninvasive biomarker and therapeutic target for nonalcoholic steatohepatitis.


Assuntos
Exossomos/metabolismo , Fatores de Transcrição Forkhead/fisiologia , Hepatócitos/metabolismo , Ativação de Macrófagos/fisiologia , MicroRNAs/fisiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Proteína Companheira de mTOR Insensível à Rapamicina/fisiologia , Transdução de Sinais/fisiologia , Animais , Masculino , MicroRNAs/biossíntese , Ratos , Ratos Sprague-Dawley
7.
Hepatobiliary Pancreat Dis Int ; 20(5): 426-432, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34246549

RESUMO

BACKGROUND: This study aimed to assess the association between metabolic syndrome (MetS) and severity of nonalcoholic fatty liver disease (NAFLD), and to discuss the pathological relevance of the diagnostic criteria in metabolic (dysfunction) associated fatty liver disease (MAFLD). METHODS: This was a multicenter, cross-sectional study. Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China. Anthropometric and metabolic parameters were collected to assess the pathological relevance. RESULTS: Of 246 enrolled patients with NAFLD, 150 (61.0%) had the comorbidity of MetS. With the increase of metabolic components, the proportions of nonalcoholic steatohepatitis (NASH) and significant fibrosis were notably increased. The comorbid three metabolic components significantly increased the proportion of NASH, and further increase of metabolic components did not increase the proportion of NASH. However, the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis. Among the 246 patients, 239 (97.2%) met the diagnostic criteria of MAFLD. Although non-MAFLD patients had less NASH, they present with similar proportion of significant fibrosis and cirrhosis. In the diagnostic criteria of MAFLD, BMI ≥ 23 kg/m2 was related to NASH (Mantel-Haenszel Common Estimate OR: 2.975; 95% CI: 1.037-8.538; P = 0.043), and T2DM was related to significant fibrosis (Mantel-Haenszel Common Estimate OR: 2.531; 95% CI: 1.388-4.613; P = 0.002). The homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 2.5 was the most significant factor for NASH (OR: 4.100; 95% CI: 1.772-9.487; P = 0.001) and significant factor for liver fibrosis (OR: 2.947; 95% CI: 1.398-6.210; P = 0.004) after the adjustments of the BMI and diabetes. CONCLUSIONS: Metabolic dysregulations are important risk factors in NAFLD progression. The insulin resistance status may play a predominant role in the progression in MAFLD patients.


Assuntos
Resistência à Insulina , Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Biópsia , China/epidemiologia , Estudos Transversais , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia
8.
Lipids Health Dis ; 18(1): 179, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31639005

RESUMO

BACKGROUND: Ceramide plays pathogenic roles in nonalcoholic fatty liver disease (NAFLD) via multiple mechanisms, and as such inhibition of ceramide de novo synthesis in the liver may be of therapeutically beneficial in patients with NAFLD. In this study, we aimed to explore whether inhibition of ceramide signaling by myriocin is beneficial in animal model of NAFLD via regulating autophagy. METHODS: Sprague Dawley rats were randomly divided into three groups: standard chow (n = 10), high-fat diet (HFD) (n = 10) or HFD combined with oral administration of myriocin (0.3 mg/kg on alternate days for 8 weeks) (n = 10). Liver histology and autophagy function were measured. HepG2 cells were incubated with fatty acid with or without myriocin treatment. Lipid accumulation and autophagy markers in the HepG2 cells were analyzed. Serum ceramide changes were studied in 104 subjects consisting healthy adults, liver biopsy-proven patients with NAFLD and liver biopsy-proven patients with chronic hepatitis B (CHB). RESULTS: Myriocin reversed the elevated body weight and serum transaminases and alleviated dyslipidemia in HFD fed rats. Myriocin treatment significantly attenuated liver pathology including steatosis, lobular inflammation and ballooning. By qPCR analysis, it was revealed that myriocin corrected the expression pattern of fatty acid metabolism associated genes including Fabp1, Pparα, Cpt-1α and Acox-2. Further, myriocin also restored the impaired hepatic autophagy function in rats with HFD-induced NASH, and this has been verified in HepG2 cells. Among the sphingolipid species that we screened in lipidomic profiles, significantly increased ceramide was observed in NASH patients as compared to the controls and non-NASH patients, regardless of whether or not they have active CHB. CONCLUSIONS: Ceramide may play an important regulatory role in the autophagy function in the pathogenesis of NASH. Hence, blockade of ceramide signaling by myriocin may be of therapeutically beneficial in NASH. TRIAL REGISTRATION: Registration ID: ChiCTR-DDT-13003983 . Data of registration: 13 May, 2013, retrospectively registered.


Assuntos
Autofagia/efeitos dos fármacos , Ceramidas/metabolismo , Dislipidemias/tratamento farmacológico , Ácidos Graxos Monoinsaturados/farmacologia , Hipolipemiantes/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Adulto , Animais , Autofagia/genética , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Estudos de Casos e Controles , Ceramidas/antagonistas & inibidores , Dieta Hiperlipídica/efeitos adversos , Dislipidemias/etiologia , Dislipidemias/genética , Dislipidemias/metabolismo , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Hepatite B Crônica/genética , Hepatite B Crônica/metabolismo , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Metabolismo dos Lipídeos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ácido Oleico/antagonistas & inibidores , Ácido Oleico/farmacologia , Oxirredutases/genética , Oxirredutases/metabolismo , PPAR alfa/genética , PPAR alfa/metabolismo , Ácido Palmítico/antagonistas & inibidores , Ácido Palmítico/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
10.
J Gastroenterol Hepatol ; 32(9): 1640-1648, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28109017

RESUMO

BACKGROUND AND AIM: Enterohepatic immunologic derangement is associated with non-alcoholic steatohepatitis. Here, we investigated whether Clostridium butyricum B1 (CB) would be an effective immune-targeted substance to attenuate steatohepatitis in mice. METHODS: Thirty mice were randomized into a control group fed with common forage, a high-fat diet (HFD) group fed an HFD for 16 weeks, and an HFD + CB group treated with CB for the latter 8 weeks. Inflammation-associated or metabolism-associated genes in the liver or epididymal fat tissue were quantified; intrahepatic and intestinal immune factors were detected. Further short-chain fatty acids in the cecal contents or liver were measured, and differentiations of T cells in vitro were analyzed. RESULTS: Characteristics of non-alcoholic steatohepatitis in the HFD group were obvious and were significantly attenuated in the HFD + CB group. The messenger RNA levels of monocyte chemotactic protein-1 and tumor necrosis factor-α in the liver and epididymal fat tissue were increased in the HFD group compared with the control group and were downregulated in the HFD + CB group. Intrahepatic and intestinal interferon-γ and interleukin (IL)-17 were significantly increased, whereas forkhead box P3, IL-4, and IL-22 were significantly decreased in the HFD group compared with the control group. However, these intrahepatic or intestinal immune changes were reversed after CB intervention. Furthermore, butyrate in the cecal content and liver of the HFD + CB group was significantly elevated. An in vitro investigation showed that sodium butyrate promoted CD4+ T cell differentiation into Th2, Th22, or Treg, whereas it inhibited CD4+ T cell differentiation into Th1 or Th17 under a cytokine milieu, which was mimicked by Trichostatin A. CONCLUSION: Clostridium butyricum B1 could attenuate HFD-induced steatohepatitis in mice partially through butyrate-induced enterohepatic immunoregulation.


Assuntos
Clostridium butyricum/imunologia , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/etiologia , Fígado Gorduroso/terapia , Intestinos/imunologia , Fígado/imunologia , Animais , Butiratos/metabolismo , Linfócitos T CD4-Positivos , Diferenciação Celular , Células Cultivadas , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Citocinas/metabolismo , Ácidos Graxos Voláteis/metabolismo , Fígado Gorduroso/imunologia , Mucosa Intestinal/metabolismo , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
11.
Toxicol Ind Health ; 32(8): 1345-1357, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25537624

RESUMO

Sulfur mustard (SM), a bifunctional alkylating agent that causes severe lung damage, is a significant threat to both military and civilian populations. The mechanisms mediating the cytotoxic effects of SM are unknown and were investigated in this study. The purpose of this study was to establish a rat model of SM-induced lung injury to observe the resulting changes in the lungs. Male rats (Sprague Dawley) were anesthetized, intratracheally intubated, and exposed to 2 mg/kg of SM by intratracheal instillation. Animals were euthanized 6, 24, 48, and 72 h post-exposure, and bronchoalveolar lavage fluid (BALF) and lung tissues were collected. Exposure of rats to SM resulted in rapid pulmonary toxicity, including partial bronchiolar epithelium cell shedding, focal ulceration, and an increased amount of inflammatory exudate and number of cells in the alveoli. There was also evidence that the protein content and cell count of BALF peaked at 48 h, and the alveolar septum was widened and filled with lymphocytes. SM exposure also resulted in partial loss of type I alveolar epithelial cell membranes, fuzzy mitochondrial cristae, detachment and dissociation of ribosomes attached to the surface of rough endoplasmic reticulum, cracked, missing, and disorganized microvilli of type II alveolar epithelial cells, and increased apoptotic cells in the alveolar septum. The propylene glycol control group, however, was the same as the normal group. These data demonstrate that the mechanism of a high concentration of SM (2 mg/kg) induced acute lung injury include histologic changes, inflammatory reactions, apoptosis, oxidative stress, and nuclear DNA damage; the degree of injury is time dependent.


Assuntos
Lesão Pulmonar Aguda/induzido quimicamente , Alquilantes/toxicidade , Substâncias para a Guerra Química/toxicidade , Modelos Animais de Doenças , Pulmão/efeitos dos fármacos , Gás de Mostarda/toxicidade , Mucosa Respiratória/efeitos dos fármacos , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/imunologia , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/ultraestrutura , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Líquido da Lavagem Broncoalveolar/química , Dano ao DNA , Retículo Endoplasmático Rugoso/efeitos dos fármacos , Retículo Endoplasmático Rugoso/imunologia , Retículo Endoplasmático Rugoso/metabolismo , Retículo Endoplasmático Rugoso/ultraestrutura , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/ultraestrutura , Ativação Linfocitária/efeitos dos fármacos , Masculino , Microscopia Eletrônica de Transmissão , Microvilosidades/efeitos dos fármacos , Microvilosidades/imunologia , Microvilosidades/metabolismo , Microvilosidades/ultraestrutura , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/imunologia , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/ultraestrutura , Organismos Livres de Patógenos Específicos
12.
Plant Foods Hum Nutr ; 71(4): 347-354, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27663717

RESUMO

As the aging of the world's population is becoming increasingly serious, dementia-related diseases have become a hot topic in public health research. In recent years, human epidemiological studies have focused on lipid metabolism disorders and dementia. The efficacy of phytosterol intake as a cholesterol-lowering agent has been demonstrated. Phytosterols directly serve as ligands of the nuclear receptors, peroxisome proliferator-activated receptors (PPARs), activating Sirtuin 1 (SIRT-1), which are involved in the regulation of lipid metabolism and the pathogenesis of dementia. Moreover, phytosterols mediate cell and membrane cholesterol efflux or beta amyloid (Aß) metabolism, which have preventative and therapeutic effects on dementia. Additionally, incorporation of plant sterols in lipid rafts can effectively reduce dietary fat and alter the dietary composition of fiber, fat and cholesterol to regulate appetite and calories. Overall, the objectives of this review are to explore whether phytosterols are a potentially effective target for the prevention of dementia and to discuss a possible molecular mechanism by which phytosterols play a role in the pathogenesis of dementia via the PPARs-SIRT-1 pathway.


Assuntos
Demência/prevenção & controle , Metabolismo dos Lipídeos/efeitos dos fármacos , Fitosteróis/farmacologia , Animais , Anticolesterolemiantes/química , Anticolesterolemiantes/farmacologia , Colesterol/metabolismo , Dieta , Gorduras na Dieta/administração & dosagem , Modelos Animais de Doenças , Homeostase/efeitos dos fármacos , Humanos , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Fitosteróis/química , Sirtuína 1/metabolismo
13.
Food Sci Nutr ; 12(4): 2523-2536, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38628206

RESUMO

Allicin is a safe herbal extract believed to have antitumor effects, which, however, remain unclear. The aim of the present work was to discuss Allicin antitumor effects on cervical cancer using cell experiments. Using Hela and Siha to our research objectives in our study, first step, difference concentration of Allicin (20, 40, and 80 µM) treated Hela and Siha cell lines, and next step, discuss circEIF4G2 effects in Allicin antitumor effects in Hela and Siha cell lines; the cell proliferation and EdU-positive cell number by CCK-8 and EdU staining; cell apoptosis rate by flow cytometry; invasion cell number by transwell assay; wound healing rate by wound healing assay; and relative mRNA and protein levels using qRT-PCR and WB assay. With Allicin supplement, the cell proliferation and EdU-positive cell number were significantly depressed with cell apoptosis rate significantly increasing; invasion cell number and wound healing rate significantly suppressed with circEIF4G2 mRNA expression significantly down-regulation (p < .05, respectively). However, there was no significant difference among Allicin, si-circEIF4G2, and Allicin+si-circEIF4G2 in cell biological activities including cell proliferation, apoptosis, invasion and migration, and relative gene and protein expression. Allicin depresses biological activities of cervical cancer cells through down-regulating circEIF4G2/HOXA1/AKT/mTOR.

14.
Sci Rep ; 14(1): 16469, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014128

RESUMO

Tectonic plate motions drive the earthquake cycle, as they result in the slow accrual and sudden release of energy along plate boundaries. Steadiness of plate motions over the earthquake cycle is a central tenet of the plate tectonics theory and has long been a main pillar in models of earthquake genesis, or of plate-margins seismic potential inferred from slip-deficit estimates. The advent of geodesy in the geosciences and the availability of multi-year-long series of position measurements permit tracking the motions of tectonic plates from before to after the time of significant seismic events that occur along their margins. Here, we present evidence that large earthquakes are capable of modifying the motions of entire microplates. We use high precision Global Navigation Satellite System (GNSS) position time-series covering the periods 2001-2004 and 2014-2017 to demonstrate that, contrary to the tenet above, the South China microplate motion changed after the 2008 M W 7.9 Great Wenchuan earthquake. The GNSS data and associated uncertainties indicate a plate motion slowdown of up to 20% that is beyond the possible impact of data noise and is thus tectonically meaningful. We use quantitative models of torque balance to show that generating this kinematic change requires a force upon the South China microplate compatible with that imparted by the Great Wenchuan earthquake of 2008. The existence of a kinematic signal linked to the earthquake cycle that impacts an entire microplate might offer an additional, novel perspective to assessing the hazards of earthquake-prone tectonic regions.

15.
Obesity (Silver Spring) ; 32(7): 1349-1361, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38816990

RESUMO

OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming an escalating health problem in pediatric populations. This study aimed to investigate the role of N-acetyltransferase 10 (NAT10) in maternal high-fat diet (HFD)-induced MASLD in offspring at early life. METHODS: We generated male hepatocyte-specific NAT10 knockout (Nat10HKO) mice and mated them with female Nat10fl/fl mice under chow or HFD feeding. Body weight, liver histopathology, and expression of lipid metabolism-associated genes (Srebp1c, Fasn, Pparα, Cd36, Fatp2, Mttp, and Apob) were assessed in male offspring at weaning. Lipid uptake assays were performed both in vivo and in vitro. The mRNA stability assessment and RNA immunoprecipitation were performed to determine NAT10-regulated target genes. RESULTS: NAT10 deletion in hepatocytes of male offspring alleviated perinatal lipid accumulation induced by maternal HFD, decreasing expression levels of Srebp1c, Fasn, Cd36, Fatp2, Mttp, and Apob while enhancing Pparα expression. Furthermore, Nat10HKO male mice exhibited reduced lipid uptake. In vitro, NAT10 promoted lipid uptake by enhancing the mRNA stability of CD36 and FATP2. RNA immunoprecipitation assays exhibited direct interactions between NAT10 and CD36/FATP2 mRNA. CONCLUSIONS: NAT10 deletion in offspring hepatocytes ameliorates maternal HFD-induced hepatic steatosis through decreasing mRNA stability of CD36 and FATP2, highlighting NAT10 as a potential therapeutic target for pediatric MASLD.


Assuntos
Dieta Hiperlipídica , Fígado Gorduroso , Hepatócitos , Metabolismo dos Lipídeos , Fígado , Camundongos Knockout , Animais , Dieta Hiperlipídica/efeitos adversos , Masculino , Feminino , Camundongos , Gravidez , Fígado/metabolismo , Fígado/patologia , Hepatócitos/metabolismo , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Acetiltransferases/genética , Acetiltransferases/metabolismo , Antígenos CD36/metabolismo , Antígenos CD36/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Efeitos Tardios da Exposição Pré-Natal , PPAR alfa/metabolismo , PPAR alfa/genética , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/etiologia
16.
Front Microbiol ; 14: 1109803, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36825089

RESUMO

Endosymbionts play crucial roles in various physiological activities within insect hosts. The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama, is an important vector for Candidatus Liberibacter asiaticus (CLas), a fatal pathogenic bacterial agent causing the disease Huanglongbing in the citrus industry. This study combines high-throughput sequencing of 16S ribosomal RNA amplicons to explore how CLas affects the bacterial community in different color morphs (blue, gray), genders, and tissues (cuticle, gut, mycetome, Malpighian tubule, ovary, and testis) of ACP. We found that there was no significant differences in the bacterial community diversity and CLas acquired ratio between the different color morphs and genders of ACP adults. However, acquiring CLas could promote the adult bacterial community's diversity and richness more than in the uninfected condition. The presence of CLas could increase the Wolbachia and unclassified_Enterobacteriaceae proportions more than in the uninfected condition. The bacterial community diversity in the CLas infected tissues of ovary and cuticle, was lower than the uninfected condition, but the richness of all tissues was not different between the infected and uninfected conditions. CLas could also change the bacterial structure in different tissues and make the bacterial relationship network simpler than it is in an uninfected condition. Furthermore, we used quantitative real-time PCR to assess the dynamic changes of Wolbachia in CLas uninfected and infected color morphs and tissues of ACP. The results showed that Wolbachia titers were significantly higher in CLas infected adults than in uninfected adults. In different tissues, the Wolbachia titers in the testis, ovary, and Malpighian tubule were higher than their uninfected counterparts. Our results provide essential knowledge for understanding the symbionts of the ACP and how CLas affects the bacterial community of the ACP.

17.
Microbiol Spectr ; : e0529822, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36975996

RESUMO

Insects are associated with diverse microbial communities that can have substantial effects on hosts. Here, we characterized the bacterial communities in the Asian citrus psyllid (ACP), Diaphorina citri (Hemiptera: Psyllidae), a major vector of the devastating pathogen "Candidatus Liberibacter asiaticus," which causes citrus Huanglongbing (HLB). In total, 256 ACP individuals across 15 field sites and one laboratory population in China were sequenced. The results showed that the bacterial community diversity was the highest in the Guilin population (average Shannon index, 1.27), and the highest value for richness was found in the Chenzhou population (average Chao1 index, 298). The bacterial community structures of the field-collected populations were significantly different, and all of them harbored Wolbachia, which was assigned to strain ST-173. Structural equation models revealed that the dominant Wolbachia strain had a significantly negative correlation with the annual mean temperature. In addition, the results obtained with populations infected with "Ca. Liberibacter asiaticus" indicated that in total, 140 bacteria could be involved in interactions with this bacterium. The ACP field populations harbored a more diverse bacterial community than the laboratory population, and the relative occurrences of some symbionts differed significantly. However, the bacterial community of the ACP laboratory colony was connected in a more complex network structure (average degree, 54.83) than that of the field populations (average degree, 10.62). Our results provide evidence that environmental factors can influence the bacterial community structure and bacterial relative abundance in ACP populations. This is likely due to the adaptation of ACPs to local environments. IMPORTANCE The Asian citrus psyllid (ACP) is an important vector of the HLB pathogen, which is a major threat to citrus production around the world. Bacterial communities harbored by insects could be affected by different environmental factors. Understanding these factors that affect the bacterial community of the ACP could be important for the better management of HLB transmission. This work surveyed ACP field populations in mainland China in order to explore the bacterial community diversity of different populations and the potential relationships between environmental factors and predominant symbionts. We have assessed the differences in ACP bacterial communities and identified the prevalent Wolbachia strains in the field. In addition, we compared the bacterial communities of ACP field-collected and laboratory populations. Comparing populations subjected to contrasting conditions could help us to better understand how the ACP adapts to local environmental conditions. Our study provides new insights into how environmental factors influence the bacterial community of the ACP.

18.
J Dig Dis ; 24(6-7): 408-418, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37529891

RESUMO

OBJECTIVES: To determine whether hyperammonemia has a direct impact on steatohepatitis in mice fed with a high-fat diet (HFD). METHODS: Male C57BL/6 mice were divided into two groups receiving either chow diet or HFD. After 12-week NASH modeling, hyperammonemia was induced by intragastric administration of ammonium chloride solution (NH4 Cl) or liver-specific carbamoyl phosphate synthetase 1 (Cps1) knockdown. In vitro experiments were performed in HepG2 cells induced by free fatty acid (FFA) and NH4 Cl. RESULTS: NH4 Cl administration led to increased levels of plasma and hepatic ammonia in NASH mice. NH4 Cl-induced hyperammonemia did not influence liver histological changes in mice fed with HFD; however, elevated plasma cholesterol level, and an increasing trend of liver lipid content were observed. No significant effect of hyperammonemia on hepatic inflammation and fibrosis in NASH mice was found. In vitro cell experiments showed that NH4 Cl treatment failed to increase the lipid droplet content and the expressions of de novo lipogenesis genes in HepG2 cells induced by FFA. The knockdown of Cps1 in HFD-fed mice resulted in elevated plasma ammonia levels but did not cause histological change in the liver. CONCLUSIONS: Our study revealed a limited role of ammonia in aggravating the progression of NASH. Further studies are needed to clarify the role and mechanism of ammonia in NASH development.


Assuntos
Hiperamonemia , Hepatopatia Gordurosa não Alcoólica , Masculino , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hiperamonemia/complicações , Hiperamonemia/metabolismo , Amônia/metabolismo , Camundongos Endogâmicos C57BL , Fígado/patologia , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças
19.
Hepatol Int ; 17(6): 1416-1428, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37728728

RESUMO

BACKGROUND AND AIM: Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease in adolescent and adult population. However, the epidemiologic data of MAFLD in prepubertal children remain limited. This study aimed to investigate the prevalence and incidence of MAFLD and assess the role of anthropometric parameters in identifying and predicting MAFLD in this population. METHODS: Children from the Shanghai Birth Cohort Study who underwent an 8-year follow-up with anthropometric measurements and transient elastography FibroScan-502 examination (M probe, Echosens, Paris, France) were enrolled. Some of them also completed a 5-year follow-up. Diagnosis of fatty liver disease (FLD) was based on the controlled attenuation parameter (CAP) value exceeding 248 dB/m, and MAFLD was defined as FLD combined with obesity or central obesity. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic accuracy of anthropometric parameters for MAFLD. RESULTS: A total of 848 children (431 boys) from the Shanghai Birth Cohort Study were followed up for 8 years, and among them, 385 children (189 boys) also participated in the 5-year follow-up. The prevalence of FLD and MAFLD at 5 years old was 3.90% and 0.52%, respectively, while at 8 years old, the prevalence rates increased to 5.07% for FLD and 3.42% for MAFLD. The 8-year-old children with MAFLD exhibited significantly higher weight, body mass index (BMI), chest circumference, waist circumference, hip circumference, waist-to-height ratio, waist-to-hip ratio, and liver stiffness measurement compared to those without MAFLD (all p < 0.05). The incidence rates of FLD and MAFLD at 8 years old, considering the 5-year follow-up data, were 3.78% (14/370) and 3.13% (12/383), respectively. Obese or centrally obese children at 5 years old had a higher incidence of FLD and MAFLD at the 8-year follow-up. Waist circumference and BMI showed significant associations with the presence and incidence of MAFLD, respectively, with the largest AUC values in ROC curve analysis. In addition, chest circumference was significantly associated with MAFLD in obese children. CONCLUSION: This study provides insights into the incidence and prevalence of MAFLD in prepubertal children. It underscores the importance of anthropometric parameters in identifying and predicting MAFLD in this population. Further research encompassing a broader age range and incorporating these indicators and additional metabolic markers is necessary to enhance the understanding and management of MAFLD in children.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Obesidade Infantil , Masculino , Adulto , Adolescente , Humanos , Criança , Pré-Escolar , Obesidade Infantil/epidemiologia , Obesidade Infantil/complicações , Obesidade Infantil/diagnóstico , Incidência , Prevalência , Coorte de Nascimento , Estudos de Coortes , China/epidemiologia , Índice de Massa Corporal , Hepatopatia Gordurosa não Alcoólica/complicações , Razão Cintura-Estatura
20.
Viruses ; 15(8)2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37632047

RESUMO

Hantaviridae currently encompasses seven genera and 53 species. Multiple hantaviruses such as Hantaan virus, Seoul virus, Dobrava-Belgrade virus, Puumala virus, Andes virus, and Sin Nombre virus are highly pathogenic to humans. They cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome or hantavirus pulmonary syndrome (HCPS/HPS) in many countries. Some hantaviruses infect wild or domestic animals without causing severe symptoms. Rodents, shrews, and bats are reservoirs of various mammalian hantaviruses. Recent years have witnessed significant advancements in the study of hantaviruses including genomics, taxonomy, evolution, replication, transmission, pathogenicity, control, and patient treatment. Additionally, new hantaviruses infecting bats, rodents, shrews, amphibians, and fish have been identified. This review compiles these advancements to aid researchers and the public in better recognizing this zoonotic virus family with global public health significance.


Assuntos
Quirópteros , Orthohantavírus , Vírus de RNA , Animais , Humanos , Saúde Pública , Musaranhos , Orthohantavírus/genética
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