RESUMO
The gut microbiota is essential for providing colonization resistance against pathogens. Dietary sugars markedly shift the composition of the intestinal microbiota and alter host susceptibility to enteric infections. Here, we demonstrate the effect of L-arabinose on bacterial infection by using a mouse infection model with Salmonella enterica serovar Typhimurium (S. Tm). In the presence of microbiota, L-arabinose induces a dramatic expansion of Enterobacteriaceae, thereby decreasing the microbiota diversity and causing more severe systemic infection. However, L-arabinose supplementation does not alter the disease progression of Salmonella infection in a microbiota-depleted mouse model. More importantly, short-term supplementation of L-arabinose fails to exert anti-diabetic effects in Salmonella-infected hyperglycemia mice and still promotes infection. Overall, our work reveals that a high intake of dietary L-arabinose supports a bloom of Enterobacteriaceae in Salmonella-infected gut, further accelerating the process of systemic infection.IMPORTANCEL-arabinose is a promising natural sweetener and food additive for the regulation of hyperglycemia. Since diabetic subjects are more susceptible to infections, the safety of dietary L-arabinose in diabetic patients experiencing infection remains a concern. Our findings reveal that L-arabinose exacerbates Salmonella infection outcome by inducing gut microbiota dysbiosis in mice. High dietary intake of L-arabinose may be deleterious for diabetic individuals undergoing infection.
Assuntos
Arabinose , Disbiose , Microbioma Gastrointestinal , Infecções por Salmonella , Salmonella typhimurium , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Disbiose/microbiologia , Arabinose/farmacologia , Camundongos , Infecções por Salmonella/microbiologia , Salmonella typhimurium/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Masculino , Enterobacteriaceae/efeitos dos fármacosRESUMO
Transition-metal-based oxygen evolution reaction (OER) catalysts have attracted widespread attention due to their inexpensive prices, unique layered structures, and rich active sites. Currently, designing low-cost, sustainable, and simple synthesis methods is essential for the application of transition-metal-based catalysts. Here, magnetic field (MF)-assisted chemical corrosion, as a novel technology, is adopted to construct superior OER electrocatalysts. The produced Ni(Fe)(OH)2-Fe2O3 electrode exhibits an overpotential of 272 mV at a current density of 100 mA cm-2, presenting a 64 mV reduction compared to the electrode without an MF. The experimental results indicate that an MF can induce the directional growth of Fe2O3 rods and reduce their accumulation. In addition, an external MF is beneficial for the lattice dislocation of the obtained catalysts, which can increase the surface free energy, thus reducing the activation energy and accelerating the electrochemical reaction kinetics. This work effectively combines a magnetic field with chemical corrosion and electrochemical energy, which offers a novel strategy for the large-scale development of environmentally friendly and superior electrocatalysts.
RESUMO
BACKGROUND: The association between change in lifestyle and cognitive impairment remains uncertain. OBJECTIVES: To investigate the association of change in lifestyle with cognitive impairment. METHODS: In this study, 4 938 participants aged 65 or older were involved from the Chinese Longitudinal Healthy Longevity Survey for years 2008-2018. A weighted healthy lifestyle score was derived from 4 lifestyle factors (smoking, alcohol consumption, physical activity, and diet). Multivariable Cox proportional hazards regression models were applied to investigate the associations between 3-year changes in healthy lifestyle (2008-2011) and cognitive impairment (2011-2018). RESULTS: Researchers documented 833 new-onset of cognitive impairments more than 20 097 person-years of follow up. Compared with those in the persistently unhealthy group, those in the improved and persistently healthy groups had a lower risk of cognitive impairment, with the multivariate-adjusted hazard ratios (HRs) of 0.67 (95% confidence interval (CI): 0.55, 0.83) and 0.53 (95% CI: 0.40, 0.71), respectively. Furthermore, a significant interaction was observed between change in lifestyle and sex (p-interactionâ =â .032); the HRs were 0.48 (95% CI, 0.34, 0.69) for the improved group and 0.41 (95% CI: 0.26, 0.64) for persistently healthy group among male vs 0.81 (95% CI, 0.63, 1.04) and 0.64 (95% CI, 0.44, 0.92) among female, respectively. CONCLUSIONS: This study suggests that improving or maintaining a healthy lifestyle can significantly mitigate the risk of cognitive impairment in Chinese older adults. Additionally, researcher's findings emphasize the significance of maintaining a healthy lifestyle and highlights the potential positive impact of improving previous unhealthy habits, especially for older women.
Assuntos
Disfunção Cognitiva , Estilo de Vida Saudável , Humanos , Masculino , Feminino , Disfunção Cognitiva/epidemiologia , Idoso , China/epidemiologia , Estudos Longitudinais , Fatores de Risco , Exercício Físico , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/epidemiologia , Modelos de Riscos Proporcionais , Estudos de Coortes , População do Leste AsiáticoRESUMO
The enrichment of organic matter is the foundation for a high-quality shale deposition. It is generally believed that high productivity and persistent anoxic conditions facilitate the preservation and enrichment of organic matter. However, there is a lack of investigation into how the dynamic combination of productivity and anoxia affects organic matter enrichment. Here, the black shales of the Wufeng Formation and Longmaxi Formation in the western Chongqing area were selected, where oceanic anoxia and high productivity evolved as a function of the water depth. The main findings were as follows: (1) the distribution of high-quality shales in the Upper Ordovician Wufeng Formation and the Lower Silurian Longmaxi Formation is closely related to the oxygen minimum zone (OMZ), indicating that the physicochemical conditions within the OMZ zone facilitated the development of high-quality shale; (2) in the late period of the Wufeng Formation, intense ocean upwelling in the middle shelf and outer shelf regions caused high productivity where thick-bedded high-quality shales were deposited; and (3) in the early period of the Longmaxi Formation, ocean upwelling weakened, accompanied by the expansion of the OMZ to shallow water regions, and high-quality shales were widely distributed. Based on the above findings, two depositional models were proposed to account for the formation of high-quality shales, and it is suggested that intense ocean upwelling during the late period of the Wufeng Formation and OMZ expansion during the early period of the Longmaxi Formation played crucial roles in facilitating the formation of high-quality shales. These two models present the spatial and temporal variability of high-quality shale development for the first time and can guide shale gas exploration and development strategies.
RESUMO
The evidence regarding the effects of blood pressure changes on older individuals remains inconclusive, and the impact of frailty throughout the life course is not known. We investigated the associations of different change patterns of blood pressure during 3-year intervals with frailty and mortality. Participants included 7335 persons from 2008 to 2014 of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Change in blood pressure was calculated as the difference between follow-up and baseline. Frailty was evaluated using a 40-item frailty index. Mortality status was ascertained up to December 31, 2014. The mean age of participants was 82.6 ± 10.7 years. The optimal blood pressure level (SBP, 130-150 mmHg; DBP, 70-90 mmHg) was associated with the lowest risk of frailty while decreasing follow-up SBP and DBP were significantly correlated with frailty. Lower baseline blood pressure levels (SBP < 130 mmHg; DBP < 70 mmHg) were associated with decreased mortality risk when participants increased their blood pressure to optimal levels during follow-up SBP and DBP (0.78, 0.63-0.98), compared to maintaining a steady low SBP (< 130 mmHg) and DBP (< 70 mmHg). For those with DBP around 70-90 mmHg, decreasing follow-up DBP (< 70 mmHg) was associated with higher mortality (1.23, 1.07-1.42) compared to maintaining stable follow-up DBP (70-90 mmHg). These results remain significant after adjusting for frailty. Optimal blood pressure levels were associated with the lowest risk of frailty. The association between lower blood pressure and increased mortality risk persisted even after accounting for frailty. We used a nationally representative longitudinal cohort study by using 2008-2014 of the Chinese Longitudinal Healthy Longevity in China. Change in blood pressure was calculated as the difference between follow-up and baseline. We investigated the associations of different change patterns of blood pressure during 3-year intervals with frailty and mortality.
Assuntos
Pressão Sanguínea , Fragilidade , Humanos , Masculino , Feminino , Pressão Sanguínea/fisiologia , Idoso , China/epidemiologia , Fragilidade/mortalidade , Idoso de 80 Anos ou mais , Estudos Longitudinais , Estudos de Coortes , Hipertensão/mortalidade , Hipertensão/fisiopatologia , Fatores de Risco , Longevidade , Idoso Fragilizado/estatística & dados numéricos , MortalidadeRESUMO
OBJECTIVES: The magnesium depletion score (MDS) is considered more reliable than traditional approaches for predicting magnesium deficiency in humans. We explored the associations of MDS and dietary magnesium intake with diabetes. METHODS: We obtained data from 18,853 participants in the National Health and Nutrition Examination Survey 2011-2018. Using multivariate regression and stratified analysis, we investigated the relationships of both MDS and magnesium intake with diabetes. To compute prevalence ratios (PRs), we employed modified Poisson or log-binomial regression. We characterized the non-linear association between magnesium intake and diabetes using restricted cubic spline analysis. RESULTS: Participants with MDS ≥2 exhibited a PR of 1.26 (95% confidence interval [CI], 1.19 to 1.34) for diabetes. Per-standard deviation (SD) increase in dietary magnesium intake was associated with a lower prevalence of diabetes (PR, 0.91; 95% CI, 0.87 to 0.96). Subgroup analyses revealed a positive association between MDS ≥2 and diabetes across all levels of dietary magnesium intake, including the lowest (PR, 1.35; 95% CI, 1.18 to 1.55), middle (PR, 1.23; 95% CI, 1.12 to 1.35), and highest tertiles (PR, 1.25; 95% CI, 1.13 to 1.37; pinteraction<0.001). Per-SD increase in magnesium intake was associated with lower diabetes prevalence in participants with MDS <2 (PR, 0.92; 95% CI, 0.87 to 0.98) and those with MDS ≥2 (PR, 0.91; 95% CI, 0.84 to 0.98; pinteraction=0.030). CONCLUSIONS: MDS is associated with diabetes, particularly among individuals with low magnesium intake. Adequate dietary magnesium intake may reduce diabetes risk, especially in those with high MDS.
Assuntos
Diabetes Mellitus , Deficiência de Magnésio , Magnésio , Inquéritos Nutricionais , Humanos , Feminino , Masculino , Magnésio/administração & dosagem , Adulto , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Diabetes Mellitus/epidemiologia , Deficiência de Magnésio/epidemiologia , Prevalência , Dieta/estatística & dados numéricos , Idoso , Adulto Jovem , Estudos TransversaisRESUMO
OBJECTIVES: Research indicates adverse childhood experiences (ACEs) were associated with subjective cognitive decline (SCD), with higher ACEs reported by sexual minoritized individuals (i.e. lesbian, gay, and bisexual; LGB). This study aimed to explore the relationships between ACEs and SCD based on sexual orientation in middle-aged and older adults. METHODS: The study included 76,592 participants from the 2019-2020 Behavioral Risk Factor Surveillance Survey (BRFSS). Multivariate logistic regressions analyzed ACEs status, score, and type associations with SCD. RESULTS: 2.18% of the participants identified as sexual minoritized individuals. More sexual minoritized individuals reported SCD compared to heterosexual individuals (10.70% for heterosexuals; 17.27% for sexual minoritized individuals). Positive association between SCD and ACEs status (OR = 2.18, 95%CI: 1.09-4.40) was identified among sexual minoritized individuals. CONCLUSIONS: The association between ACEs and SCD was strong in both heterosexual and sexual minoritized populations. Given the higher experience of ACEs among sexual minoritized adults, the subsequent frequency of SCD among these adults also may be higher. CLINICAL IMPLICATIONS: Sexual minoritized older adults may have a history of numerous ACEs, which could contribute to a greater burden of SCD. Clinicians and other stakeholders may wish to consider relationships between ACEs and SCD based on sexual orientation.
RESUMO
The geroscience hypothesis states that a therapy that prevents the underlying aging process should prevent multiple aging related diseases. The mTOR (mechanistic target of rapamycin)/insulin and NAD+ (nicotinamide adenine dinucleotide) pathways are two of the most validated aging pathways. Yet, it's largely unclear how they might talk to each other in aging. In genome-wide CRISPRa screening with a novel class of N-O-Methyl-propanamide-containing compounds we named BIOIO-1001, we identified lipid metabolism centering on SIRT3 as a point of intersection of the mTOR/insulin and NAD+ pathways. In vivo testing indicated that BIOIO-1001 reduced high fat, high sugar diet-induced metabolic derangements, inflammation, and fibrosis, each being characteristic of non-alcoholic steatohepatitis (NASH). An unbiased screen of patient datasets suggested a potential link between the anti-inflammatory and anti-fibrotic effects of BIOIO-1001 in NASH models to those in amyotrophic lateral sclerosis (ALS). Directed experiments subsequently determined that BIOIO-1001 was protective in both sporadic and familial ALS models. Both NASH and ALS have no treatments and suffer from a lack of convenient biomarkers to monitor therapeutic efficacy. A potential strength in considering BIOIO-1001 as a therapy is that the blood biomarker that it modulates, namely plasma triglycerides, can be conveniently used to screen patients for responders. More conceptually, to our knowledge BIOIO-1001 is a first therapy that fits the geroscience hypothesis by acting on multiple core aging pathways and that can alleviate multiple conditions after they have set in.
RESUMO
Driven by the energy crisis and environmental pollution, developing sustainable clean energy is an effective strategy to realize carbon neutrality. Electrocatalytic reactions are crucial to sustainable energy conversion and storage technologies, and advanced electrocatalysts are required to improve the sluggish electrocatalytic reactions. The magnetic field, as a thermodynamic parameter independent of temperature and pressure, is vital in the construction of electrocatalysts and enhancement of electrocatalysis. In this Review, the recent progress of magnetic field-assisted construction of electrocatalysts and enhancement of electrocatalysis is comprehensively summarized. Originating from the structure-activity-performance relationship of electrocatalysts, the fundamentals of the magnetic field-induced construction of electrocatalysts, including the magnetocaloric effect, nucleation and growth, and phase regulation, have been illustrated. In addition, the magnetic effect on the electrocatalytic reaction, namely, the magnetothermal, magnetohydrodynamic and micro magnetohydrodynamic, Maxwell stress, Kelvin force, and spin selection effects, are discussed. Finally, the perspective and challenges for magnetic field-assisted construction of electrocatalysts and enhancement of electrocatalysis are proposed.
RESUMO
Amyloid-ß oligomer (AßO) is widely regarded as a reliable biomarker for the early diagnosis of Alzheimer's disease (AD). In this study, a signal on-off ratiometric electrochemical immunosensor has been developed for ultrasensitive detection of AßO. To achieve the dual-signal ratiometric strategy, ultrasmall copper sulfide nanoparticle-engineered covalent organic framework hybrid nanocomposites (CuS@COFs) were utilized as excellent electrocatalysts toward hydroquinone (HQ) oxidation to produce detectable signals. Meanwhile, electroactive thionine (Thi) and Aß antibody-modified gold nanoparticles (Thi-AuNPs-Ab bioconjugates) were designed as another electrochemical indicator. Based on these two signals, an ultrasensitive sandwich-like electrochemical immunosensor was established for AßO detection. The introduction of AßO resulted in a remarkable decline in the electrochemical signal of HQ but an increase in the signal of Thi. Under optimum conditions, the ratios between the double signals (IThi/IHQ) showed a proportional linear relationship with the AßO concentration (1 pM-1 µM) with a low detection limit of 0.4 pM (S/N = 3), and the biosensor was able to determine the content of AßO in real cerebrospinal fluid samples with satisfactory results. The ratiometric strategy proposed in our study offers a sensitive and efficient approach for early diagnosis of AD, and this work will promote the further applications of engineered COFs in electrochemical sensors.
Assuntos
Doença de Alzheimer , Técnicas Biossensoriais , Nanopartículas Metálicas , Estruturas Metalorgânicas , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Técnicas Biossensoriais/métodos , Cobre , Técnicas Eletroquímicas/métodos , Ouro/química , Humanos , Imunoensaio/métodos , Limite de Detecção , Nanopartículas Metálicas/química , Estruturas Metalorgânicas/química , SulfetosRESUMO
Developing efficient catalysts is vital for the application of electrochemical sensors. Metal-organic frameworks (MOFs), with high porosity, large specific surface area, good conductivity, and biocompatibility, have been widely used in catalysis, adsorption, separation, and energy storage applications. In this invited review, the recent advances of a novel MOF-based catalysts in electrochemical sensors are summarized. Based on the structure-activity-performance relationship of MOF-based catalysts, their mechanism as electrochemical sensor, including metal cations, synthetic ligands, and structure, are introduced. Then, the MOF-based composites are successively divided into metal-based, carbon-based, and other MOF-based composites. Furthermore, their application in environmental monitoring, food safety control, and clinical diagnosis is discussed. The perspective and challenges for advanced MOF-based composites are proposed at the end of this contribution.
RESUMO
The mitochondrial pyruvate carrier (MPC) is an inner mitochondrial membrane complex that plays a critical role in intermediary metabolism. Inhibition of the MPC, especially in liver, may have efficacy for treating type 2 diabetes mellitus. Herein, we examined the antidiabetic effects of zaprinast and 7ACC2, small molecules which have been reported to act as MPC inhibitors. Both compounds activated a bioluminescence resonance energy transfer-based MPC reporter assay (reporter sensitive to pyruvate) and potently inhibited pyruvate-mediated respiration in isolated mitochondria. Furthermore, zaprinast and 7ACC2 acutely improved glucose tolerance in diet-induced obese mice in vivo. Although some findings were suggestive of improved insulin sensitivity, hyperinsulinemic-euglycemic clamp studies did not detect enhanced insulin action in response to 7ACC2 treatment. Rather, our data suggest acute glucose-lowering effects of MPC inhibition may be due to suppressed hepatic gluconeogenesis. Finally, we used reporter sensitive to pyruvate to screen a chemical library of drugs and identified 35 potentially novel MPC modulators. Using available evidence, we generated a pharmacophore model to prioritize which hits to pursue. Our analysis revealed carsalam and six quinolone antibiotics, as well as 7ACC1, share a common pharmacophore with 7ACC2. We validated that these compounds are novel inhibitors of the MPC and suppress hepatocyte glucose production and demonstrated that one quinolone (nalidixic acid) improved glucose tolerance in obese mice. In conclusion, these data demonstrate the feasibility of therapeutic targeting of the MPC for treating diabetes and provide scaffolds that can be used to develop potent and novel classes of MPC inhibitors.
Assuntos
Proteínas de Transporte de Ânions , Proteínas de Transporte da Membrana Mitocondrial , Transportadores de Ácidos Monocarboxílicos , Obesidade , Quinolonas , Animais , Proteínas de Transporte de Ânions/antagonistas & inibidores , Proteínas de Transporte de Ânions/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Dieta , Glucose/metabolismo , Camundongos , Camundongos Obesos , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/antagonistas & inibidores , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Transportadores de Ácidos Monocarboxílicos/antagonistas & inibidores , Transportadores de Ácidos Monocarboxílicos/metabolismo , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Ácido Pirúvico/metabolismo , Quinolonas/farmacologiaRESUMO
The key biological "drivers" that are responsible for reverse left ventricle (LV) remodeling are not well understood. To gain an understanding of the role of the autophagy-lysosome pathway in reverse LV remodeling, we used a pathophysiologically relevant murine model of reversible heart failure, wherein pressure overload by transaortic constriction superimposed on acute coronary artery (myocardial infarction) ligation leads to a heart failure phenotype that is reversible by hemodynamic unloading. Here we show transaortic constriction + myocardial infarction leads to decreased flux through the autophagy-lysosome pathway with the accumulation of damaged proteins and organelles in cardiac myocytes, whereas hemodynamic unloading is associated with restoration of autophagic flux to normal levels with incomplete removal of damaged proteins and organelles in myocytes and reverse LV remodeling, suggesting that restoration of flux is insufficient to completely restore myocardial proteostasis. Enhancing autophagic flux with adeno-associated virus 9-transcription factor EB resulted in more favorable reverse LV remodeling in mice that had undergone hemodynamic unloading, whereas overexpressing transcription factor EB in mice that have not undergone hemodynamic unloading leads to increased mortality, suggesting that the therapeutic outcomes of enhancing autophagic flux will depend on the conditions in which flux is being studied.
RESUMO
BACKGROUND: Porcine circovirus type 3 (PCV3) has been an emerging porcine virus spread around the world. The conserved DNA sequence of PCV3 enabled good performance in molecular biological assays. RESULT: In this study, we developed a real-time fluorescence PCR assay for the detection of PCV3. The conserved region within Capsid genome of PCV3 was selected for the design of primer pairs and probes. After optimizing, a primer pair and probe was screened, providing high sensitivity (10 copies/µL) and specificity (no cross reaction with other porcine viruses or common bacterium). In addition, this method was applied in the detection of 110 clinical samples, and the performance was compared with other previously reported PCR and real-time PCR methods. This method provided higher detection rate. CONCLUSION: A real-time fluorescence PCR assay has been developed for the detection of PCV3, with high sensitivity and specificity, exhibiting good performance in detecting clinical samples.
Assuntos
Infecções por Circoviridae/veterinária , Circovirus/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Doenças dos Suínos/virologia , Animais , Proteínas do Capsídeo/genética , Infecções por Circoviridae/diagnóstico , Infecções por Circoviridae/virologia , Circovirus/genética , Primers do DNA , Fluorescência , Reação em Cadeia da Polimerase em Tempo Real/métodos , Sensibilidade e Especificidade , Sus scrofa , Suínos , Doenças dos Suínos/diagnósticoRESUMO
Background: Acute kidney injury (AKI) is a significant cause of morbidity and mortality, especially in sepsis patients. Early prediction of AKI can help physicians determine the appropriate intervention, and thus, improve the outcome. This study aimed to develop a nomogram to predict the risk of AKI in sepsis patients (S-AKI) in the initial 24 h following admission.Methods: Sepsis patients with AKI who met the Sepsis 3.0 criteria and Kidney Disease: Improving Global Outcomes criteria in the Massachusetts Institute of Technology critical care database, Medical Information Mart for Intensive Care (MIMIC-III), were identified for analysis. Data were analyzed using multiple logistic regression, and the performance of the proposed nomogram was evaluated based on Harrell's concordance index (C-index) and the area under the receiver operating characteristic curve.Results: We included 2917 patients in the analysis; 1167 of 2042 patients (57.14%) and 469 of 875 patients (53.6%) had AKI in the training and validation cohorts, respectively. The predictive factors identified by multivariate logistic regression were blood urea nitrogen level, infusion volume, lactate level, weight, blood chloride level, body temperature, and age. With the incorporation of these factors, our model had well-fitted calibration curves and achieved good C-indexes of 0.80 [95% confidence interval (CI): 0.78-0.82] and 0.79 (95% CI: 0.76-0.82) in predicting S-AKI in the training and validation cohorts, respectively.Conclusion: The proposed nomogram effectively predicted AKI risk in sepsis patients admitted to the intensive care unit in the first 24 h.
Assuntos
Injúria Renal Aguda/diagnóstico , Unidades de Terapia Intensiva , Nomogramas , Sepse/complicações , Injúria Renal Aguda/etiologia , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Hospitalização , Humanos , Modelos Logísticos , Masculino , Massachusetts , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Fatores de TempoRESUMO
PURPOSES: To investigate the protective effect of exogenous neutrophil gelatinase-associated lipocalin (NGAL) on the lipopolysaccharide-induced injury of renal tubular epithelial cells and its regulation of autophagy. METHODS: Renal tubular epithelial cells were treated with lipopolysaccharide (LPS) at different concentrations (0-100 µg/mL) and at different times (0-24 h), the expression of NGAL was detected to determine the optimal time and concentration of LPS treatment. The NGAL gene knockdown lentivirus (NGAL-RNAi) was constructed and verified its knockdown rate and inhibition effect. Renal tubular epithelial cells were randomly divided into Control group, LPS group, LPS + NGAL group, NGAL-RNAi + LPS group, and NGAL-RNAi + LPS + NGAL group. Western blot and immunofluorescence tested the expression of autophagy-associated proteins, the changes in the number of autophagosomes were observed by electron microscopy, analyzed the role of exogenous NGAL. RESULTS: The study showed the expression of autophagy-associated proteins (LC3-II and Beclin-1) in NGAL-RNAi + LPS group was significantly lower than the LPS group (P < 0.0100). The expression of LC3-II and Beclin-1 in the NGAL-RNAi + LPS + NGAL group was significantly higher than the NGAL-RNAi + LPS group (P < 0.0100). After the addition of exogenous NGAL, the autophagosomes in the LPS + NGAL group and the NGAL-RNAi + LPS + NGAL group were significantly increased under the electron microscope compared with the LPS group and the NGAL-RNAi + LPS group, and the cell proliferation rate and cell viability was significantly higher than unjoined groups (P < 0.0500). CONCLUSION: NGAL knockdown can significantly reduce the level of autophagy and decrease the proliferation rate and viability of cells.The addition of exogenous NGAL can increase the level of autophagy. This suggests that NGAL may play a protective role in the LPS-induced injury of renal tubular epithelial cells by promoting autophagy.
Assuntos
Autofagia/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Lipocalina-2/farmacologia , Lipopolissacarídeos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Autofagossomos/efeitos dos fármacos , Autofagossomos/metabolismo , Autofagossomos/ultraestrutura , Autofagia/genética , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Lipocalina-2/genética , Lipocalina-2/metabolismo , Microscopia Eletrônica , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia , Interferência de RNARESUMO
Several recent studies have suggested that compounds known as endocrine-disrupting chemicals (EDCs) can promote obesity by serving as ligands for nuclear receptors, including the peroxisome proliferator-activated receptor γ (PPARγ) and the glucocorticoid receptor (GR). Thiazolidinedione insulin sensitizers, which act as ligands for PPARγ, also interact with and regulate the activity of the mitochondrial pyruvate carrier (MPC). We evaluated whether several EDCs might also affect MPC activity. Most of the EDCs evaluated did not acutely affect pyruvate metabolism. However, the putative endocrine disruptors tributyltin (TBT) and tolylfluanid (TF) acutely and markedly suppressed pyruvate metabolism in isolated mitochondria. Using mitochondria isolated from brown adipose tissue in mice with adipocyte-specific deletion of the MPC2 protein, we determined that the effect of TF on pyruvate metabolism required MPC2, whereas TBT did not. We attempted to determine whether the obesogenic effects of TF might involve MPC2 in adipose tissue. However, we were unable to replicate the published effects of TF on weight gain and adipose tissue gene expression in wild-type or fat-specific MPC2 knockout mice. Treatment with TF modestly enhanced adipogenic gene expression in vitro but had no effect on GR activation or phosphorylation in cultured cells. These data suggest that TF may affect mitochondrial pyruvate metabolism via the MPC complex but also call into question whether this compound affects GR activity and is obesogenic in mice.
Assuntos
Disruptores Endócrinos/farmacologia , Proteínas de Membrana Transportadoras/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Pró-Proteína Convertase 2/metabolismo , Sulfonamidas/farmacologia , Toluidinas/farmacologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Tecido Adiposo Marrom , Animais , Proteínas de Transporte de Ânions , Transporte Biológico/efeitos dos fármacos , Feminino , Proteínas de Membrana Transportadoras/genética , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/genética , Proteínas de Transporte da Membrana Mitocondrial , Transportadores de Ácidos Monocarboxílicos , Pró-Proteína Convertase 2/genética , Ácido Pirúvico/metabolismoRESUMO
We recently reported a very unusual temperature dependence of the rate of thermal reaction of wild type bovine rhodopsin: the Arrhenius plot exhibits a sharp "elbow" at 47 °C and, in the upper temperature range, an unexpectedly large activation energy (114 ± 8 kcal/mol) and an enormous prefactor (1072±5 s-1). In this report, we present new measurements and a theoretical model that establish convincingly that this behavior results from a collective, entropy-driven breakup of the rigid hydrogen bonding networks (HBNs) that hinder the reaction at lower temperatures. For E181Q and S186A, two rhodopsin mutants that disrupt the HBNs near the binding pocket of the 11-cis retinyl chromophore, we observe significant decreases in the activation energy (â¼90 kcal/mol) and prefactor (â¼1060 s-1), consistent with the conclusion that the reaction rate is enhanced by breakup of the HBN. The results provide insights into the molecular mechanism of dim-light vision and eye diseases caused by inherited mutations in the rhodopsin gene that perturb the HBNs.
Assuntos
Mutação , Rodopsina/química , Rodopsina/genética , Temperatura , Animais , Bovinos , Ligação de Hidrogênio , CinéticaRESUMO
The aim of the present study was to determine the effect of a small dose of aspirin on a quantitative test of 24-h urinary protein in patients with hypertension in pregnancy. In total, 224 patients with hypertension in pregnancy were continuously selected and were randomly divided into the control group (50 cases with conventional therapy), aspirin 50 mg/day group (60 cases), aspirin 75 mg/day group (58 cases), and aspirin 100 mg/day group (56 cases). Clinical effects were compared from 16 gestational weeks to childbirth. According to the comparison in the four groups, there was no statistical difference in the mean arterial pressure, pre-eclampsia rate, gestational weeks, and caesarean section rate (p>0.05). The 24-h urinary protein and endothelin-1 (ET-1) level were significantly decreased following treatment, and were less than the control and 50 mg/day groups. The superoxide dismutase (SOD) level was significantly increased, and higher than the control and 50 mg/day groups. In terms of the 75 and 100 mg/day, control and 50 mg/day groups, there was no statistical difference (p>0.05). A comparison of the complication rate in the four groups of fetuses during the perinatal period, no statistical difference was observed (p>0.05). Thus, the results show that, regarding patients with hypertension in pregnancy, 75 mg/day aspirin can decrease the 24-h urinary protein, SOD, and ET-1 level. However, the results remain to be confirmed to improve maternal and infant outcome in delivery.
RESUMO
Correction for 'A narrow amide I vibrational band observed by sum frequency generation spectroscopy reveals highly ordered structures of a biofilm protein at the air/water interface' by Zhuguang Wang et al., Chem. Commun., 2016, 52, 2956-2959.