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1.
Nat Commun ; 15(1): 4813, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844461

RESUMO

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) poses a major threat to the global swine industry, yet effective prevention and control measures remain elusive. This study unveils Nitazoxanide (NTZ) as a potent inhibitor of PRRSV both in vitro and in vivo. Through High-Throughput Screening techniques, 16 potential anti-PRRSV compounds are identified from a library comprising FDA-approved and pharmacopeial drugs. We show that NTZ displays strong efficacy in reducing PRRSV proliferation and transmission in a swine model, alleviating viremia and lung damage. Additionally, Tizoxanide (TIZ), the primary metabolite of NTZ, has been identified as a facilitator of NMRAL1 dimerization. This finding potentially sheds light on the underlying mechanism contributing to TIZ's role in augmenting the sensitivity of the IFN-ß pathway. These results indicate the promising potential of NTZ as a repurposed therapeutic agent for Porcine Reproductive and Respiratory Syndrome (PRRS). Additionally, they provide valuable insights into the antiviral mechanisms underlying NTZ's effectiveness.


Assuntos
Antivirais , Ensaios de Triagem em Larga Escala , Nitrocompostos , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Tiazóis , Animais , Vírus da Síndrome Respiratória e Reprodutiva Suína/efeitos dos fármacos , Nitrocompostos/farmacologia , Suínos , Antivirais/farmacologia , Ensaios de Triagem em Larga Escala/métodos , Síndrome Respiratória e Reprodutiva Suína/tratamento farmacológico , Síndrome Respiratória e Reprodutiva Suína/virologia , Tiazóis/farmacologia , Replicação Viral/efeitos dos fármacos , Linhagem Celular , Viremia/tratamento farmacológico , Viremia/virologia
2.
Environ Sci Technol ; 58(19): 8182-8193, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38691136

RESUMO

As an alternative plasticizer to conventional phthalates, di(2-ethylhexyl) terephthalate (DEHTP) has attracted considerable concerns, given its widespread detection in the environment and humans. However, the potential toxicity, especially liver toxicity, posed by DEHTP remains unclear. In this study, based on the 2017-2018 National Health and Nutrition Examination Survey, two metabolites of DEHTP, i.e., mono(2-ethyl-5-hydroxyhexyl) terephthalate (MEHHTP) and mono(2-ethyl-5-carboxypentyl) terephthalate (MECPTP), were found to be present in the urine samples of nearly all representative U.S. adults. Moreover, a positive linear correlation was observed between the concentrations of the two metabolites and the risk of nonalcoholic fatty liver disease (NAFLD) in the population. Results of weighted quantile sum and Bayesian kernel machine regression indicated that MEHHTP contributed a greater weight to the risk of NAFLD in comparison with 12 conventional phthalate metabolites. In vitro experiments with hepatocyte HepG2 revealed that MEHHTP exposure could increase lipogenic gene programs, thereby promoting a dose-dependent hepatic lipid accumulation. Activation of liver X receptor α may be an important regulator of MEHHTP-induced hepatic lipid disorders. These findings provide new insights into the liver lipid metabolism toxicity potential of DEHTP exposure in the population.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Ácidos Ftálicos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Humanos , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/metabolismo , Masculino , Adulto , Feminino
3.
Immunol Cell Biol ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38804132

RESUMO

M1/M2 macrophage polarization plays an important role in regulating the balance of the microenvironment within tissues. Moreover, macrophage polarization involves the reprogramming of metabolism, such as glucose and lipid metabolism. Transcriptional coactivator B-cell lymphoma-3 (Bcl-3) is an atypical member of the IκB family that controls inflammatory factor levels in macrophages by regulating nuclear factor kappa B pathway activation. However, the relationship between Bcl-3 and macrophage polarization and metabolism remains unclear. In this study, we show that the knockdown of Bcl-3 in macrophages can regulate glycolysis-related gene expression by promoting the activation of the nuclear factor kappa B pathway. Furthermore, the loss of Bcl-3 was able to promote the interferon gamma/lipopolysaccharide-induced M1 macrophage polarization by accelerating glycolysis. Taken together, these results suggest that Bcl-3 may be a candidate gene for regulating M1 polarization in macrophages.

4.
Small ; : e2309397, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38644343

RESUMO

The utilization of solar-thermal energy and universal cold energy has led to many innovative designs that achieve effective temperature regulation in different application scenarios. Numerous studies on passive solar heating and radiation cooling often operate independently (or actively control the conversion) and lack a cohesive framework for deep connections. This work provides a concise overview of the recent breakthroughs in solar heating and radiation cooling by employing a mechanism material in the application model. Furthermore, the utilization of dynamic Janus-like behavior serves as a novel nexus to elucidate the relationship between solar heating and radiation cooling, allowing for the analysis of dynamic conversion strategies across various applications. Additionally, special discussions are provided to address specific requirements in diverse applications, such as optimizing light transmission for clothing or window glass. Finally, the challenges and opportunities associated with the development of solar heating and radiation cooling applications are underscored, which hold immense potential for substantial carbon emission reduction and environmental preservation. This work aims to ignite interest and lay a solid foundation for researchers to conduct in-depth studies on effective and self-adaptive regulation of cooling and heating.

5.
Food Funct ; 15(8): 4436-4445, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38563400

RESUMO

Background: Garlic has antioxidant, anti-inflammatory, cardiovascular improvement and other beneficial effects on human health. However, few studies have evaluated the association of garlic intake with the risk of depressive symptoms. The aim of this prospective cohort was to examine the association between the frequency of raw garlic consumption and depressive symptoms in the general adult population. Methods: A total of 7427 participants (mean ± standard deviation: 39.7 ± 10.5 years) without baseline depressive symptoms were included in the cohort study. Garlic consumption was assessed using a validated food frequency questionnaire, and depressive symptoms were assessed by a Chinese version of the Self-rating Depression Scale score (SDS score ≥ 45). Multivariable Cox proportional hazards models were used to determine the association between garlic consumption and the risk of depressive symptoms. Results: This study identified 1070 cases of depressive symptoms during a median follow-up of 2.0 years, with a depression prevalence of 73.4 cases per 1000 person-years. After multivariate adjustment, the hazard ratios (95% confidence intervals) for depressive symptoms in males were 1.00 (reference) for almost never, 1.05 (0.84, 1.32) for ≤1 time per week, 1.16 (0.90, 1.49) for 2-3 times per week, and 1.31 (0.97, 1.78) for ≥4 times per week, and in females, they were 1.00 (reference) for almost never, 0.85 (0.69, 1.06) for ≤1 time per week, 0.72 (0.54, 0.97) for 2-3 times per week, and 0.78 (0.53, 1.13) for ≥4 times per week. Conclusion: In a large general population, we demonstrate for the first time that moderate raw garlic consumption is associated with a reduced risk of depressive symptoms in females, but not in males. Additional prospective studies with long-term follow-up and randomized controlled trials are necessary to confirm the preliminary results of the current study.


Assuntos
Depressão , Alho , Humanos , Alho/química , Masculino , Feminino , Adulto , Depressão/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos de Coortes , Modelos de Riscos Proporcionais , Fatores de Risco , China/epidemiologia
6.
Front Vet Sci ; 11: 1372032, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38681852

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) remains one of the major threats to swine industry, resulting in huge economic losses worldwide. Currently, PRRSV has diversified into multiple lineages with characteristics of extensive recombination in China. In this research, three virus strains were isolated and four virus whole genome sequences were generated and analyzed from clinical samples collected in Gansu province of China in 2023. The four virus strains were designated GSTS4-2023, GSLX2-2023, GSFEI2-2023 and GSBY4-2023. Phylogenetic analysis based on ORF5 sequences showed that GSTS4-2023, GSLX2-2023, GSFEI2-2023 and GSBY4-2023 shared 91.7, 91.2, 93.2 and 92.9% homology with NADC30 strain respectively, and belonged to lineage 1 of PRRSV-2. In addition, one amino acid deletion was observed at position 33 in ORF5 of GSTS4-2023, GSLX2-2023 and GSFEI2-2023. Moreover, amino acid alignment of the four strains showed a typical discontinuous 131-amino acid (aa) deletion in NSP2 for NADC30-like virus strains. Recombination analysis revealed that all four strains originated from NADC30 (lineage 1), with their minor parents coming from JXA1-like strains (lineage 8), VR-2332-like strains (lineage5) and QYYZ-like strains (lineage3). Finally, the three isolated virus strains, GSTS4-2023, GSLX2-2023 and GSFEI2-2023 showed relatively low levels of replication in cell culture. Our findings provide important implications for the field epidemiology of PRRSV.

7.
Antiviral Res ; 225: 105868, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38490343

RESUMO

Porcine Reproductive and Respiratory Syndrome (PRRS) presents a formidable viral challenge in swine husbandry. Confronting the constraints of existing veterinary pharmaceuticals and vaccines, this investigation centers on Caffeic Acid Phenethyl Ester (CAPE) as a prospective clinical suppressant for the Porcine Reproductive and Respiratory Syndrome Virus (PRRSV). The study adopts an integrated methodology to evaluate CAPE's antiviral attributes. This encompasses a dual-phase analysis of CAPE's interaction with PRRSV, both in vitro and in vivo, and an examination of its influence on viral replication. Varied dosages of CAPE were subjected to empirical testing in animal models to quantify its efficacy in combating PRRSV infections. The findings reveal a pronounced antiviral potency, notably in prophylactic scenarios. As a predominant component of propolis, CAPE stands out as a promising candidate for clinical suppression, showing exceptional effectiveness in pre-exposure prophylaxis regimes. This highlights the potential of CAPE in spearheading cutting-edge strategies for the management of future PRRSV outbreaks.


Assuntos
Ácidos Cafeicos , Álcool Feniletílico/análogos & derivados , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Drogas Veterinárias , Suínos , Animais , Estudos Prospectivos , Drogas Veterinárias/farmacologia , Replicação Viral , Antivirais/farmacologia
9.
Int J Biol Macromol ; 258(Pt 1): 128883, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38141715

RESUMO

Multilayer nanocomposite film made of different materials has multifunctional properties and is applied in the field of flexible electronic devices. Herein, hydroxyethyl cellulose (HEC) and boron nitride nanosheets (BNNS) were used as the matrix and thermal conductivity material of the HEC/BNNS (HB) insulation layer and were combined with conductive blade structure graphene/silver nanowires (GA) film to prepare a three-layer HB/GA20/HB film. Using the high mechanical properties of the HEC based film, the tensile strength of the three-layer film is increased to 22.0 MPa, 633 % higher than that of the pure conductive film. The sensor prepared by multilayer film has good bending sensing performance (1500 cycles) and electromagnetic shielding performance (29.3 dB). The heating temperature of HB/GA20/HB film heater is up to 107.9 °C at 20 V. In the HB/GA20/HB film, the external HB layer provides insulation, thermal conductivity and physical support, and the internal GA layer with good conductive and sensing properties is combined to build a multi-functional sensor, which can be applied as a mobile sensor, heater and electromagnetic shielding material in the flexible wearable field.


Assuntos
Grafite , Nanofios , Prata , Celulose , Condutividade Elétrica
10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013089

RESUMO

Objective@#Based on 3D printing technology, explore the precision of a perforator vessel location guide plate for fibular musculocutaneous flaps before the transplantation of fibular osteocutaneous flaps and evaluate its application effects.@*Methods@#This study was reviewed and approved by the ethics committee, and informed consent was obtained from the patients. From May 2019 to October 2022, 14 patients with jaw defects who needed to undergo fibular perforator flap transplantation at the First Affiliated Hospital of Xinjiang Medical University were selected. For the seven patients in the guide plate group, CTA was combined with Mimics software to reconstruct both lower limbs, and the perforator vessel positioning guide for locating perforator vessels was designed; the two ends of the guide plate were designed as fixed ends, with the upper end fixed to the knee joint and the lower end fixed to the ankle joint, and the guide plate was fabricated by a 3D printer. For the seven patients in the control group, a conventional handheld Doppler probe was used for perforator vessel location. The average operation time, bleeding volume, recovery time, deviation of perforator vessel location, postoperative flap-related complications, postoperative donor site shape satisfaction, and lower extremity functional scale (LEFS) score were recorded. SPSS 25.0 software was used for statistical analysis.@*Results@#The average operation time, bleeding volume, recovery time, deviation of perforator vessel location and postoperative donor site shape satisfaction were significantly better in the guide plate group than in the control group (P<0.05); moreover, the differences in postoperative flap-related complications and LEFS scores were not statistically significant (P>0.05).@*Conclusion@#Based on 3D printing technology, fibular musculocutaneous flap perforator vessels can be more accurately located using a guide plate and the knee and ankle as fixed points, and this method can effectively stabilize the guide position, prevent soft tissue offset, and improve positioning accuracy and thus deserves to be generalized.

11.
Food Funct ; 14(24): 10955-10963, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38010908

RESUMO

Background: Whole-grain contains a range of beneficial nutrients, which are thought to play a role in the prevention of chronic diseases. However, the association between whole-grain consumption and the risk of developing carotid atherosclerosis (CA) has not been sufficiently elucidated. We, therefore, conducted this study to investigate the relationship between whole-grain consumption and CA in the general adult population. Methods: This prospective cohort study included a total of 2166 participants (19.2-84.6 years, 55.0% men) without a history of cardiovascular disease, cancer, and CA at baseline. A validated food frequency questionnaire was used to assess whole-grain consumption. Measurements of CA include carotid intima-media thickness (IMT) and carotid plaque. IMT thickening is defined as: IMT ≥ 1.0 mm or a carotid bifurcation IMT ≥ 1.2 mm. Carotid plaque is defined as: distinct area protruding ≥1.5 mm into the vascular lumen of the carotid artery. Cox proportional hazards regression models were used to examine the association of whole-grain consumption with incident CA. Results: A total of 538 (341 men) first incident cases of CA occurred during 5585 person-years of follow-up (median follow-up: 4.2 years). After adjusting for demographic characteristics, lifestyle factors, dietary intake, individual and family history of disease, the multivariable HRs (95% CIs) for incident CA were 1.00 (reference) for <1 time per week, 1.10 (0.85, 1.43) for 1 time per week, 0.95 (0.75, 1.20) for 2-6 times per week, and 1.12 (0.80, 1.56) for ≥1 times per day, respectively (P for trend = 0.99). Similar results were observed in stratified analyses by the main covariates and sensitivity analyses. Conclusion: Our data indicate that whole-grain consumption had no significant association with the risk of CA in an adult Chinese population. In our study population, there is a low consumption of whole-grain, which may limit our ability to see an association. Further cohort studies or randomized controlled trials are needed to confirm our results.


Assuntos
Doenças das Artérias Carótidas , Placa Aterosclerótica , Masculino , Adulto , Humanos , Feminino , Estudos de Coortes , Espessura Intima-Media Carotídea , Estudos Prospectivos , Fatores de Risco , Doenças das Artérias Carótidas/epidemiologia , Inflamação/epidemiologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-37903218

RESUMO

Lessons from the recent COVID-19 pandemic underscore the importance of rapidly developing an efficacious vaccine and its immediate administration for prophylaxis. Oral vaccines are of particular interest, as the presence of healthcare professionals is not needed for this stress-free vaccination approach. In this study, we designed a chitosan (CH)-alginate (AL) complex carrier system encapsulating an inactivated influenza virus vaccine (A/PR/8/34, H1N1), and the efficacy of these orally administered nanocomposite vaccines was evaluated in mice. Interestingly, CH-AL complexes were able to load large doses of vaccine (≥90%) with a stable dispersion. The encapsulated vaccine was protected from gastric acid and successfully released from the nanocomposite upon exposure to conditions resembling those of the small intestines. Scanning electron microscopy of the CH-virus-AL complexes revealed that the connections between the lumps became loose and widened pores were visible on the nanocomposite's surface at pH 7.4, thereby increasing the chance of virus release into the surroundings. Orally inoculating CH-virus-AL into mice elicited higher virus-specific IgG compared to the unimmunized controls. CH-virus-AL immunization also enhanced CD4 and CD8 T cell responses while diminishing lung virus titer, inflammatory cytokine production, and body weight loss compared to the infection control group. These results suggest that chitosan-alginate polymeric nanocomposites could be promising delivery complexes for oral influenza vaccines.

13.
Environ Pollut ; 338: 122685, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37804905

RESUMO

In this work, 45 cosmetic samples were collected from China, and 27 target per- and polyfluoroalkyl substances (PFAS) were analyzed by ultrahigh-performance liquid chromatography-high resolution mass spectrometry. PFAS were found in all samples, including the products marketed for pregnant women, and the total concentrations of PFAS measured in each sample were in the range of 4.05 - 94.9 ng/g. Short-chain perfluorinated carboxylic acids were the dominant compounds contributing to over 60% of the total content. Perfluorobutanoic acid, with high placental transfer efficiency, was the major PFAS in cosmetics for pregnant women. Three emerging PFAS, 2-perfluorohexyl ethanoic acid, 3-perfluoropentyl propanoic acid (5:3) and perfluoro-2-propoxypropanoic acid, were also identified in the cosmetic samples at quantifiable levels. Significantly, positive correlations between individual PFAS were observed, indicating that there may be a common source for PFAS in these samples. Statistical analyses suggested that using plastic containers and precursor substances may be potential sources of PFAS in terminal products, and product aging may increase PFAS levels. From the PFAS analysis of the cosmetics, the margin of safety (MoS) and hazard quotient (HQ) were calculated to assess human health risks through dermal exposure by using these products. Although the MoS and HQ values obtained were deemed acceptable, the cumulative effect caused by composite and long-term exposure to these contaminants needs to be given greater attention by health authorities.


Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Humanos , Feminino , Gravidez , Placenta/química , Cromatografia Líquida , China , Fluorocarbonos/análise , Ácidos Alcanossulfônicos/análise
14.
Plant Physiol Biochem ; 203: 108048, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37757719

RESUMO

The redistribution of nonstructural carbohydrates (NSCs) in rice (Oryza sativa) sheaths contributes greatly to grain filling. Sucrose nonfermenting-1-related protein kinase 1 (SnRK1) regulates sheath-to-panicle transport of NSCs during rice grain filling; however, it is unknown whether elevated activity of SnRK1 in sheaths improves NSC transport and grain filling. Expression of OsSnRK1a is mainly responsible for regulating SnRK1 activity in rice sheaths. Analysis of transgenic rice plants containing the OsSnRK1a promoter::GUS construct indicated that OsSnRK1a is widely expressed in rice. Notably, OsSnRK1a is highly expressed in mesophyll cells of sheaths. Therefore, a green tissue promoter specifically expressed in sheaths and leaf parenchyma cells and phloem tissue was used to over-express OsSnRK1a in japonica rice. The transgenic lines exhibited increased SnRK1a expression and SnRK1 activity in sheaths. The NSC and starch in the transgenic lines and WT all showed accumulation before heading and during the early-filling stage, and declining at the peak filling stage. But the starch and NSC content in transgenic lines was lower than that of WT. Moreover, the transgenic lines showed lower sucrose contents and higher sucrose efflux rates. The accelerated sheath NSC transport improved grain filling, and stimulated panicle development in transgenic lines. SnRK1a expression and SnRK1 activity were also increased in the leaves of transgenic lines, which improved leaf photosynthetic activity and contributed to optimal grain filling and panicle development. These results verify the promotion of high SnRK1 activity in sheath NSC transport, and also provide a new approach to improving sheath NSC transport and rice yield.

15.
Sci Total Environ ; 905: 167313, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-37742961

RESUMO

Per- and polyfluoroalkyl substances (PFAS) have attracted increasing attention due to their environmental persistence and potential toxicity. Diet is one of the main routes of human exposure to PFAS, particularly through the consumption of animal-derived foods (e.g., aquatic products, livestock and poultry, and products derived from them). This review summarizes the source, bioaccumulation, and distribution of PFAS in animal-derived foods and key influential factors. In most environmental media, perfluorooctanoic acid and perfluorooctane sulfonate are the dominant PFAS, with the levels of short-chain PFAS such as perfluorobutyric acid and perfluorohexane sulfonate surpassing them in some watersheds and coastal areas. The presence of PFAS in environmental media is mainly influenced by suspended particulate matter, microbial communities as well as temporal and spatial factors, such as season and location. Linear PFAS with long carbon chains (C ≥ 7) and sulfonic groups tend to accumulate in organisms and contribute significantly to the contamination of animal-derived foods. Furthermore, PFAS, due to their protein affinity, are prone to accumulate in the blood and protein-rich tissues such as the liver and kidney. Species differences in PFAS bioaccumulation are determined by diet, variances in protein content in the blood and tissues and species-specific activity of transport proteins. Carnivorous fish usually show higher PFAS accumulation than omnivorous fish. Poultry typically metabolize PFAS more rapidly than mammals. PFAS exposures in the processing of animal-derived foods are also attributable to the migration of PFAS from food contact materials, especially those in higher-fat content foods. The human health risk assessment of PFAS exposure from animal-derived foods suggests that frequent consumption of aquatic products potentially engender greater risks to women and minors than to adult males. The information and perspectives from this review would help to further identify the toxicity and migration mechanism of PFAS in animal-derived foods and provide information for food safety management.


Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Adulto , Masculino , Animais , Humanos , Feminino , Bioacumulação , Ácidos Alcanossulfônicos/análise , Material Particulado , Dieta , Fluorocarbonos/análise , Ingestão de Alimentos , Mamíferos
17.
Metabolism ; 146: 155660, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37451670

RESUMO

BACKGROUND AND OBJECTIVES: MicroRNA-dependent regulation of hepatic lipid metabolism has been recognized recently as a key pathological mechanism contributing to the development of NAFLD. However, whether miR-32-5p (miR-32) plays a role in lipid metabolism or contributes to NAFLD remains unclear. METHODS AND RESULTS: A marked increase in miR-32 expression was observed in liver samples from patients and mice with NAFLD, as well as in palmitate-induced hepatocytes. Hepatocyte-specific miR-32 knockout (miR-32-HKO) dramatically ameliorated hepatic steatosis and metabolic disorders in high-fat diet-fed mice. Conversely, hepatic miR-32 overexpression markedly exacerbated the progression of these abnormalities. Further, combinational analysis of transcriptomics and lipidomics suggested that miR-32 was a key trigger for de novo lipogenesis in the liver. Mechanistically, RNA sequencing, luciferase assay and adenovirus-mediated downstream gene rescue assay demonstrated that miR-32 directly bound to insulin-induced gene 1 (INSIG1) and subsequently activated sterol regulatory element binding protein-mediated lipogenic gene programs, thereby promoting hepatic lipid accumulation and metabolic disorders. Notably, pharmacological administration of miR-32 antagonist significantly inhibited palmitate-induced triglyceride deposition in hepatocytes and markedly mitigated hepatic steatosis and metabolic abnormalities in obesity-associated NAFLD mice. CONCLUSION: miR-32 is an important checkpoint for lipogenesis in the liver, and targeting miR-32 could be a promising therapeutic approach for NAFLD treatment.


Assuntos
Hiperlipidemias , MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Humanos , Lipogênese/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hiperlipidemias/metabolismo , Células Hep G2 , Fígado/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Dieta Hiperlipídica/efeitos adversos , Palmitatos , Camundongos Endogâmicos C57BL
18.
J Psychiatr Res ; 164: 364-371, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37406500

RESUMO

Aggressive behavior of drug addicts threatens human security and social stability, and Methamphetamine (MA) addicts show especially aggressive behavior. Researches showed that the decreased activity of dorsolateral prefrontal cortex (DLPFC) is closely related to violence and aggression, and continuous transcranial direct current stimulation (tDCS) on DLPFC can increase the activity of this position. So, the purpose of this study was to investigate the effect of tDCS on DLPFC for the aggressive behavior of MA addicts. Ninety MA addicts were recruited and randomly divided into anodal tDCS group, cathode tDCS group and sham tDCS group (current intensity was set as 2 mA, 2 mA and 0 mA, respectively). The tDCS intervention was conducted twice a day for five consecutive days. Taylor Aggression Paradigm (TAP) was used to measure the proactive aggressiveness and reactive aggressiveness of MA addicts at different time points (Pretest, Day 1, and Day 5). At the same time, we also recruited 30 healthy adult males as healthy controls, and measured their aggressiveness through TAP for comparative analysis. The results showed that the aggressiveness of MA addicts was significantly higher than that of healthy controls. The aggressiveness of MA addicts was effectively reduced by the anode intervention of tDCS on the left DLPFC, especially when they were subjected to high-intensity provocation, the 2-way interaction between time and tDCS group was statistically significant (F4,164 = 2.939, P = 0.022, ηp2 = 0.067). This study can provide a reference for how to correct the aggressive behavior of MA addicts.


Assuntos
Estimulação Transcraniana por Corrente Contínua , Adulto , Humanos , Masculino , Agressão , Córtex Pré-Frontal Dorsolateral , Método Duplo-Cego , Córtex Pré-Frontal/fisiologia , Estimulação Transcraniana por Corrente Contínua/métodos , Violência
19.
Horm Metab Res ; 55(9): 634-641, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37380030

RESUMO

Hyperinsulinemia and insulin resistance in T2D have a potent suppressive effect on hepatic autophagy, however, the underlying mechanisms remain unclear. To explore the effect of insulin on hepatic autophagy and its possible signaling pathways, HL-7702 cells were treated with insulin with or without insulin signaling inhibitors. The interaction between insulin and the promoter region of GABARAPL1 was assessed through luciferase assay and EMSA. There were significant dose-dependent decreases in the number of intracellular autophagosomes and the protein levels of GABARAPL1 and beclin1 in insulin-treated HL-7702 cells. Insulin signaling inhibitors reversed the inhibitory effect of insulin on rapamycin-induced autophagy and autophagy-related gene upregulation. Insulin blocks the binding of FoxO1 to putative insulin response elements in GABARAPL1 gene promoter, leading to the repressed transcription of GABARAPL1 gene and the suppression of hepatic autophagy. Our study identified GABARAPL1 as a novel target of insulin in suppressing hepatic autophagy.


Assuntos
Insulina , Proteínas Associadas aos Microtúbulos , Insulina/farmacologia , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Transdução de Sinais/genética , Autofagia/genética , Regiões Promotoras Genéticas/genética
20.
BMC Psychiatry ; 23(1): 350, 2023 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-37210486

RESUMO

BACKGROUND: The level of depression among drug addicts is generally higher than normal. Hostility and sense of life meaning may influence depression and become risk factors for depression. This study has three research purposes. First, to analyze whether drug use can aggravate hostility and depression levels. Second, to assess whether the hostility has different effects on depression among drug addicts and non-addicts. Third, to examine whether the sense of life meaning has a mediating role between different groups (drug addicts and non-addicts). METHODS: This study was conducted from March to June 2022. 415 drug addicts (233 males and 182 females) and 411 non-addicts (174 males and 237 females) were recruited in Chengdu, Sichuan Province. After signing informed consent, their psychometric data were obtained using the Cook-Medley Hostility Scale (CMI), Beck Depression Inventory (BDI) and Meaning in Life Questionnaire (MLQ) questionnaires. Linear regression models were used to assess the impact of hostility and depression among drug addicts and non-addicts. Bootstrap mediation effect tests were used to further test the mediation effect of sense of life meaning between hostility and depression. RESULTS: The results showed four main outcomes. First, compared with non-addicts, drug addicts had higher levels of depression. Second, hostility exacerbated depression in both drug addicts and non-addicts. Compared with non-addicts, hostile affect had a greater effect on depression in drug addicts. Third, the sense of life meaning among females was higher than males. Fourth, for drug addicts, the sense of life meaning showed a mediating effect between social aversion and depression, while for non-addicts, the sense of life meaning showed a mediating effect between cynicism and depression. CONCLUSIONS: Depression is more severe in drug addicts. More attention should be paid to the mental health of drug addicts, because the elimination of negative emotions is conducive to reintegration into society. Our results provide a theoretical basis for reducing depression among drug addicts and non-addicts. As a protective factor, we can reduce their hostility and depression by improving the sense of life meaning.


Assuntos
Usuários de Drogas , Hostilidade , Masculino , Feminino , Humanos , Fatores de Risco , Psicometria , Inquéritos e Questionários
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