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1.
World J Microbiol Biotechnol ; 38(2): 34, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34989900

RESUMO

Formic acid is a representative small molecule acid in lignocellulosic hydrolysate that can inhibit the growth of Saccharomyces cerevisiae cells during alcohol fermentation. However, the mechanism of formic acid cytotoxicity remains largely unknown. In this study, RNA-Seq technology was used to study the response of S. cerevisiae to formic acid stress at the transcriptional level. Scanning electron microscopy and Fourier transform infrared spectroscopy were conducted to observe the surface morphology of yeast cells. A total of 1504 genes were identified as being differentially expressed, with 797 upregulated and 707 downregulated genes. Transcriptomic analysis showed that most genes related to glycolysis, glycogen synthesis, protein degradation, the cell cycle, the MAPK signaling pathway, and redox regulation were significantly induced under formic acid stress and were involved in protein translation and synthesis amino acid synthesis genes were significantly suppressed. Formic acid stress can induce oxidative stress, inhibit protein biosynthesis, cause cells to undergo autophagy, and activate the intracellular metabolic pathways of energy production. The increase of glycogen and the decrease of energy consumption metabolism may be important in the adaptation of S. cerevisiae to formic acid. In addition, formic acid can also induce sexual reproduction and spore formation. This study through transcriptome analysis has preliminarily reveal the molecular response mechanism of S. cerevisiae to formic acid stress and has provided a basis for further research on methods used to improve the tolerance to cell inhibitors in lignocellulose hydrolysate.

2.
J Environ Manage ; 306: 114456, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35026714

RESUMO

Pesticides play a significant role in increasing agricultural yields. However, the overuse of chemical pesticides on crops is a major challenge faced by China, which damages human health, threatens food security, and increases production costs. This paper provides empirical evidence on the relationship between crop insurance and pesticide use. Based on micro-survey data collected from 3410 households, we estimate a control function (CF) approach and find that farmers who purchase crop insurance use 33.30% lower pesticides than those who do not. A series of robustness tests confirm these findings. The results of the moderating effect analysis suggest that rice cultivation training, experience, schooling years, and agricultural laborers can negatively moderate the effect of crop insurance on pesticide use. Furthermore, we also find that the treatment effect of crop insurance is stronger for farmers who are most inclined to purchase crop insurance.

3.
Nanomedicine ; 39: 102467, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34610478

RESUMO

Various drug delivery strategies to improve cancer therapeutic efficacy have been actively investigated. One major challenge is to improve the targeting ability. Here elaborately designed nanocarriers (NCs) named as Tf-5-ALA-PTX-NCs are demonstrated to address this problem. In this nanostructure, paclitaxel (PTX) and 5-aminolevulinic acid (5-ALA) were co-encapsulated within magnetic nanocarriers to achieve synergistic chemotherapy and photodynamic therapy, while transferrin (Tf) was conjugated with modified copolymer Pluronic P123 and embedded in the surface of the nanocarriers, which endows nanocarriers with Tf targeting and magnetic targeting to enhance the anti-tumor outcome. Results demonstrated that Tf-5-ALA-PTX-NCs significantly enhanced the targeting drug delivery to MCF-7 cells and synergistically induced apoptosis and death of MCF-7 cells in vitro and highly efficient tumor ablation in vivo. Intriguingly, Tf-5-ALA-PTX-NCs have a controllable "on/off" switch to enhance the drug release. The dual-targeted nanocarriers would be a promising versatile anti-tumor drug delivery and imaging-guided cancer chemo-photodynamic synchronization therapy strategy.

4.
Diabetes ; 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34957498

RESUMO

BACKGROUND & AIMS: Hepatosteatosis, defined as excessive intrahepatic lipid accumulation, represents the first step of NAFLD. When combined with additional cellular stress, this benign status progresses to local and systemic pathological conditions such as NASH and insulin resistance. However, the molecular events directly caused by hepatic lipid build-up, in terms of its impact on liver biology and peripheral organs, remain unclear. Carnitine palmitoyltransferase 1A (CPT1A) is the rate limiting enzyme for long chain fatty acid beta-oxidation in the liver. Here we utilise hepatocyte-specific Cpt1a knockout (LKO) mice to investigate the physiological consequences of abolishing hepatic long chain fatty acid metabolism. APPROACH & RESULTS: Compared to the wild-type (WT) littermates, high fat diet (HFD)-fed LKO mice displayed more severe hepatosteatosis but were otherwise protected against diet-induced weight gain, insulin resistance, hepatic ER stress, inflammation and damage. Interestingly, increased energy expenditure was observed in LKO mice, accompanied by enhanced adipose tissue browning. RNAseq analysis revealed that the peroxisome proliferator activator alpha (PPARα)- fibroblast growth factor 21 (FGF21) axis was activated in liver of LKO mice. Importantly, antibody-mediated neutralization of FGF21 abolished the healthier metabolic phenotype and adipose browning in LKO mice, indicating that the elevation of FGF21 contributes to the improved liver pathology and adipose browning in HFD-treated LKO mice. CONCLUSIONS: Liver with deficient CPT1A expression adopts a healthy steatotic status that protects against HFD-evoked liver damage and potentiates adipose browning in an FGF21-dependent manner. Inhibition of hepatic CPT1A may serve as a viable strategy for the treatment of obesity and NAFLD.

5.
Animals (Basel) ; 11(11)2021 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-34828054

RESUMO

This study evaluated the effects of dietary gallic acid (GA) on growth performance, diarrhea incidence and plasma antioxidant status of weaned piglets regardless of whether weaning weight was high or low. A total of 120 weaned piglets were randomly allocated to four treatments in a 42-day experiment with a 2 × 2 factorial treatment arrangement comparing different weaning weights (high weight (HW) or low weight (LW), 8.49 ± 0.18 kg vs. 5.45 ± 0.13 kg) and dietary treatment (without supplementation (CT) or with supplementation of 400 mg/kg of GA). The results showed that HW piglets exhibited better growth performance and plasma antioxidant capacity. Piglets supplemented with GA had higher body weight (BW) on day 42 and average daily gain (ADG) from day 0 to 42 compared to the control piglets, which is mainly attributed to the specific improvement on BW and ADG of LW piglets by the supplementation of GA. The decreased values of diarrhea incidence were seen in piglets fed GA, more particularly in LW piglets. In addition, dietary GA numerically reduced malondialdehyde (MDA) content in plasma of LW piglets. In conclusion, our study suggests that dietary GA may especially improve the growth and health in LW weaned piglets.

6.
Diabetes ; 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34675003

RESUMO

BACKGROUND & AIMS: Hepatosteatosis, defined as excessive intrahepatic lipid accumulation, represents the first step of NAFLD. When combined with additional cellular stress, this benign status progresses to local and systemic pathological conditions such as NASH and insulin resistance. However, the molecular events directly caused by hepatic lipid build-up, in terms of its impact on liver biology and peripheral organs, remain unclear. Carnitine palmitoyltransferase 1A (CPT1A) is the rate limiting enzyme for long chain fatty acid beta-oxidation in the liver. Here we utilise hepatocyte-specific Cpt1a knockout (LKO) mice to investigate the physiological consequences of abolishing hepatic long chain fatty acid metabolism. APPROACH & RESULTS: Compared to the wild-type (WT) littermates, high fat diet (HFD)-fed LKO mice displayed more severe hepatosteatosis but were otherwise protected against diet-induced weight gain, insulin resistance, hepatic ER stress, inflammation and damage. Interestingly, increased energy expenditure was observed in LKO mice, accompanied by enhanced adipose tissue browning. RNAseq analysis revealed that the peroxisome proliferator activator alpha (PPARα)- fibroblast growth factor 21 (FGF21) axis was activated in liver of LKO mice. Importantly, antibody-mediated neutralization of FGF21 abolished the healthier metabolic phenotype and adipose browning in LKO mice, indicating that the elevation of FGF21 contributes to the improved liver pathology and adipose browning in HFD-treated LKO mice. CONCLUSIONS: Liver with deficient CPT1A expression adopts a healthy steatotic status that protects against HFD-evoked liver damage and potentiates adipose browning in an FGF21-dependent manner. Inhibition of hepatic CPT1A may serve as a viable strategy for the treatment of obesity and NAFLD.

7.
Adv Sci (Weinh) ; : e2102250, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34708591

RESUMO

The extraction of uranium from seawater, which is an abundant resource, has attracted considerable attention as a viable form of energy-resource acquisition. The two critical factors for boosting the chemical thermodynamics of uranium extraction from seawater are the availability of sufficient amounts of uranyl ions for supply to adsorbents and increased interaction temperatures. However, current approaches only rely on the free diffusion of uranyl ions from seawater to the functional groups within adsorbents, which largely limits the uranium extraction capacity. Herein, inspired by the mechanism of plant transpiration, a plant-mimetic directional-channel poly(amidoxime) (DC-PAO) hydrogel is designed to enhance the uranium extraction efficiency via the active pumping of uranyl ions into the adsorbent. Compared with the original PAO hydrogel without plant-mimetic transpiration, the uranium extraction capacity of the DC-PAO hydrogel increases by 79.33% in natural seawater and affords the fastest reported uranium extraction average rate of 0.917 mg g-1 d-1 among the most state-of-the-art amidoxime group-based adsorbents, along with a high adsorption capacity of 6.42 mg g-1 within 7 d. The results indicate that the proposed method can enhance the efficiency of solar-transpiration-based uranium extraction from seawater, particularly in terms of reducing costs and saving processing time.

8.
Phytochemistry ; 191: 112895, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34403885

RESUMO

Prenylated flavonoids, a unique class of flavonoids which combine a flavonoid skeleton and a lipophilic prenyl side-chain, possess great potential biological activities including cytotoxicity, anti-inflammation, anti-Alzheimer, anti-microbial, anti-oxidant, anti-diabetes, estrogenic, vasorelaxant and enzyme inhibition. Recently, prenylated flavonoids have become an indispensable anchor for the development of new therapeutic agents, and have received increasing from medicinal chemists. The prenylated flavonoids have been outstanding developed through isolation, semi or fully synthesis in a very short period of time, which proves the great value in medicinal chemistry researches. In this review, research progress of prenylated flavonoids including natural prenylated flavonoids, structural modification, synthetic methodologies and pharmacological activities was summarized comprehensively. Furthermore, the structure-activity relationships (SARs) of prenylated flavonoids were summarized which provided a basis for the selective design and optimization of multifunctional prenylated flavonoid derivatives for the treatment of multi-factorial diseases in clinic.


Assuntos
Antioxidantes , Flavonoides , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Flavonoides/farmacologia , Prenilação , Relação Estrutura-Atividade
9.
J Agric Food Chem ; 69(32): 9350-9361, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34369774

RESUMO

In this study, headspace solid-phase microextraction-gas chromatography-mass spectrometry, multivariate analyses, and transcriptomics were used to explore the biosynthesis of key volatiles and the formation of spores in Lentinula (L.) edodes. Among the 50 volatiles identified, 1-octen-3-ol, phenethyl alcohol, and several esters were considered key aromas because of their higher odor activity values. Eleven volatiles were screened as biomarkers by orthogonal partial least squares discriminant analysis, and hierarchical cluster analysis showed that these biomarkers could represent all volatiles to distinguish the spore release stage. The activities of lipoxygenase (LOX), hydroperoxide lyase, alcohol dehydrogenase, and alcohol acyltransferase were higher in L. edodes with spore release. Moreover, linolenic acid and phenylalanine metabolism were involved in aroma biosynthesis. One LOX-related gene and five aryl alcohol dehydrogenase-related genes could regulate the biosynthesis of 1-octen-3-ol, phenethyl alcohol, and phenylacetaldehyde. In addition, several key genes were involved in meiosis to regulate sporulation.


Assuntos
Cogumelos Shiitake , Compostos Orgânicos Voláteis , Biomarcadores , Odorantes , Esporos Fúngicos
10.
Animals (Basel) ; 11(8)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34438653

RESUMO

Isoquinoline alkaloids (IQ) exert beneficial antimicrobial and anti-inflammatory effects in livestock. Therefore, we hypothesized that supplementing sows' diets with IQ during gestation would decrease farrowing stress, affecting the piglets' development and performance. Sows were divided into: IQ1, supplemented with IQ from gestation day 80 (G80) to weaning; IQ2, supplemented from gestation day 110 (G110) to weaning, and a non-supplemented (NC) group. Sow body weight (BW), feed intake, back-fat thickness and back-muscle thickness were monitored. Cortisol, glucose and insulin were measured in sows' blood collected 5 d before, during, and after 7 d farrowing. Protein, fat, IgA and IgG were analyzed in the colostrum and milk. Piglets were monitored for weight and diarrhea score, and for ileum histology and gene expression 5 d post-weaning. IQ-supplemented sows lost less BW during lactation. Glucose and insulin levels were lower in the IQ groups compared to NC-sows 5 d before farrowing and had higher levels of protein and IgG in their colostrum. No other differences were observed in sows, nor in the measured parameters in piglets. In conclusion, IQ supplementation affected sows' metabolism, reducing body weight loss during lactation. Providing IQ to sows from their entrance into the maternity barn might be sufficient to induce these effects. IQ improved colostrum quality, increasing the protein and IgG content, improving passive immunity for piglets.

11.
Adv Sci (Weinh) ; 8(19): e2101031, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34365741

RESUMO

IRF8 is a key regulator of innate immunity receptor signaling and plays diverse functions in the development of hematopoietic cells. The effects of IRF8 on hematopoietic stem cells (HSCs) are still unknown. Here, it is demonstrated that IRF8 deficiency results in a decreased number of long-term HSCs (LT-HSCs) in mice. However, the repopulation capacity of individual HSCs is significantly increased. Transcriptomic analysis shows that IFN-γ and IFN-α signaling is downregulated in IRF8-deficient HSCs, while their response to proinflammatory cytokines is unchanged ex vivo. Further tests show that Irf8-/- HSCs can not respond to CpG, an agonist of Toll-like receptor 9 (TLR9) in mice, while long-term CpG stimulation increases wild-type HSC abundance and decreases their bone marrow colony-forming capacity. Mechanistically, as the primary producer of proinflammatory cytokines in response to CpG stimulation, dendritic cells has a blocked TLR9 signaling due to developmental defect in Irf8-/- mice. Macrophages remain functionally intact but severely reduce in Irf8-/- mice. In NK cells, IRF8 directly regulates the expression of Tlr9 and its deficiency leads to no increased IFNγ production upon CpG stimulation. These results indicate that IRF8 regulates HSCs, at least in part, through controlling TLR9 signaling in diverse innate immune cells.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34288130

RESUMO

Gallic acid is a phenolic compound that exhibits antibacterial, antioxidative and anti-inflammatory functions. In a previous study, we found that dietary supplementation with gallic acid decreased incidence of diarrhoea and protected intestinal integrity in weaning piglets. However, the underlying mechanism remains unclear. Here, a pig intestinal epithelial cell line (IPEC-J2) was used as an in vitro model to explore the antioxidant and anti-inflammatory capacity of gallic acid. IPEC-J2 cells were stimulated with hydrogen peroxide (H2 O2 ) and lipopolysaccharide (LPS) to establish oxidative and inflammatory models, respectively. Results showed that H2 O2 significantly decreased catalase (CAT) secretion and CAT mRNA abundance in the cells (p < 0.05), while pretreatment with gallic acid did not prevent the decrease in CAT expression induced by H2 O2 . However, gallic acid pretreatment mitigated the increased expression of the tumour necrosis factor-α and interleukin-8 genes caused by LPS in IPEC-J2 cells (p < 0.05). In addition, pretreatment with gallic acid significantly suppressed phosphorylation of NF-κB and IκBα in LPS-stimulated IPEC-J2 cells. Moreover, LPS stimulation decreased the protein abundance of zona occludens 1 (ZO-1) and occludin, while pretreatment with gallic acid preserved expression level of tight junction proteins ZO-1 and occludin in LPS-stimulated IPEC-J2 cells (p < 0.05). In conclusion, gallic acid may mitigate LPS-induced inflammatory responses by inhibiting the NF-κB signalling pathway, exerting positive effects on the barrier function of IPEC-J2 cells.

13.
ESC Heart Fail ; 8(4): 3037-3048, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34008352

RESUMO

OBJECTIVE: To investigate the prognostic value of elevated urinary albumin concentration (UAC) in hospitalized acute decompensated heart failure (ADHF) patients. METHODS: We measured UAC at baseline in 1818 hospitalized ADHF patients who were admitted to our Heart Failure Center. All patients were followed up for a median period of 937.5 days. The primary endpoint was a composite of all-cause death or heart transplantation (HTx) or left ventricular assist device (LVAD) implantation. RESULTS: In total, 41.5% of ADHF patients had albuminuria (UAC ≥ 20 mg/L). The median value of UAC was 15.5 mg/L. A total of 679 patients died or underwent HTx/LVAD during follow-up. The median UAC was significantly lower in non-HTx/LVAD survivors (14.3 mg/L) than in those who died or underwent HTx/LVAD (18.0 mg/L, P < 0.001). Compared with patients without albuminuria (reference, n = 1064), those with albuminuria had a 1.47-fold higher risk of all-cause death or HTx/LVAD (95% confidence interval [CI]:1.26-1.71, P < 0.001), with hazard ratios (HRs) of 1.42 (95% CI: 1.21-1.66) and 1.74 (95% CI: 1.33-2.26) in patients with microalbuminuria (20 mg/L ≤ UAC < 200 mg/L, n = 617) and macroalbuminuria (UAC ≥ 200 mg/L, n = 137), respectively (both P < 0.001). After adjustment for significant clinical risk factors, the albuminuria group had a higher risk of primary adverse events than the non-albuminuria group (HR = 1.28, 95% CI: 1.09-1.50, P = 0.003), with HRs of 1.27 [95% CI: 1.07-1.49] and 1.36 [95% CI: 1.01-1.84] in patients with microalbuminuria and macroalbuminuria, respectively (P = 0.006 and P = 0.041). The adjusted risk of primary adverse events also increased with the degree of albuminuria in the test for trend (HR = 1.21, 95% CI: 1.06-1.37, P for trend = 0.004). In the subgroup analysis, albuminuria had a significantly greater prognostic value for patients with left ventricular ejection fraction ≥ 40%, eGFR ≥ 60 mL/min/1.73 m2 , BUN/creatinine ratio ≥ 20 or NT-proBNP < 2098 pg/mL. CONCLUSION: The presence of albuminuria evaluated by UAC predicts adverse clinical outcomes in hospitalized ADHF patients.


Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Albuminas , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Humanos , Volume Sistólico , Função Ventricular Esquerda
14.
Crit Care Med ; 49(10): 1674-1683, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33935161

RESUMO

OBJECTIVES: To determine the diagnostic and clinical utility of trio-rapid genome sequencing in critically ill infants. DESIGN: In this prospective study, samples from critically ill infants were analyzed using both proband-only clinical exome sequencing and trio-rapid genome sequencing (proband and biological parents). The study occurred between April 2019 and December 2019. SETTING: Thirteen member hospitals of the China Neonatal Genomes Project spanning 10 provinces were involved. PARTICIPANTS: Critically ill infants (n = 202), from birth up until 13 months of life were enrolled based on eligibility criteria (e.g., CNS anomaly, complex congenital heart disease, evidence of metabolic disease, recurrent severe infection, suspected immune deficiency, and multiple malformations). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 202 participants, neuromuscular (45%), respiratory (22%), and immunologic/infectious (18%) were the most commonly observed phenotypes. The diagnostic yield of trio-rapid genome sequencing was higher than that of proband-only clinical exome sequencing (36.6% [95% CI, 30.1-43.7%] vs 20.3% [95% CI, 15.1-26.6%], respectively; p = 0.0004), and the average turnaround time for trio-rapid genome sequencing (median: 7 d) was faster than that of proband-only clinical exome sequencing (median: 20 d) (p < 2.2 × 10-16). The metagenomic analysis identified pathogenic or likely pathogenic microbes in six infants with symptoms of sepsis, and these results guided the antibiotic treatment strategy. Sixteen infants (21.6%) experienced a change in clinical management following trio-rapid genome sequencing diagnosis, and 24 infants (32.4%) were referred to a new subspecialist. CONCLUSIONS: Trio-rapid genome sequencing provided higher diagnostic yield in a shorter period of time in this cohort of critically ill infants compared with proband-only clinical exome sequencing. Precise and fast molecular diagnosis can alter medical management and positively impact patient outcomes.


Assuntos
Técnicas e Procedimentos Diagnósticos/tendências , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Sequenciamento Completo do Genoma/métodos , China , Estado Terminal/terapia , Humanos , Lactente , Recém-Nascido , Avaliação de Resultados em Cuidados de Saúde/métodos , Estudos Prospectivos , Fatores de Tempo , Sequenciamento Completo do Genoma/estatística & dados numéricos
15.
ACS Omega ; 6(10): 6691-6698, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33748582

RESUMO

Edible vegetable oils can provide most of the fatty acids, vitamin E, and certain phytochemicals necessary in the daily human diet to facilitate the required physiological activities. However, there are many types of edible vegetable oils on the market, and evaluating their nutritional quality is a matter of significant interest to consumers and producers. Most of the existing research studies that comparatively analyze and qualitatively describe the type, content, and proportion of nutrients in edible vegetable oil lack a comprehensive method for evaluating the nutritional quality of edible vegetable oil. Based on the physical and chemical analysis of fatty acids, vitamins, and phytochemicals in edible vegetable oil, this study aims to establish a model for a comprehensive evaluation of the nutritional quality of edible vegetable oils. The characteristic nutrients in edible vegetable oil were screened as the evaluation index, while the 2013 China Dietary Reference Intake and French Population Reference Intakes For Fatty Acids was considered the evaluation threshold. When each evaluation index in the edible vegetable oil reached the range stipulated by the reference intake of dietary nutrients, the index will get 1 point. The total score of each index was accumulated to evaluate the nutritional quality of the edible vegetable oils comprehensively. In this study, 13 edible vegetable oils, including low erucic acid rapeseed oil (in America, people usually call it canola oil), soybean oil, peanut oil, sunflower seed oil, flaxseed oil, edible blend oil, olive oil, palm oil, corn oil, camellia oil, peony seed oil, sacha inchi oil, and sesame oil, were selected as the evaluation objects because they are very common in China. Seven evaluation indexes were found for total saturated fatty acids (SFAs), atherogenic fatty acids (SFAs with 12, 14, and 16 carbon chains), monounsaturated fatty acids, polyunsaturated fatty acids like linoleic acid and α-linolenic acid, vitamin E, and phytosterol. When the evaluation index met the evaluation threshold, it was scored 1 point. Scores ranged from 2 to 6. The highest scores were obtained from peony seed oil, flaxseed oil, low erucic acid rapeseed oil, and edible blend oil all of which were 6 points. The lowest score belonged to palm oil at 2 points. The higher the score, the higher the degree of satisfaction between the various nutrients in the edible vegetable oil and the dietary reference intake of this model is. This paper establishes a new method for the nutritional evaluation of edible vegetable oils, which is convenient for comparing the overall nutritional quality of different kinds of edible vegetable oils while providing a new technique for the extensive evaluation of edible vegetable oil.

16.
Biochem Biophys Res Commun ; 545: 189-194, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33561654

RESUMO

The prevalence of obesity is increasing globally and is associated with many metabolic disorders, such as type 2 diabetes and cardiovascular diseases. In recent years, a number of studies suggest that promotion of white adipose browning represents a promising strategy to combat obesity and its related metabolic disorders. The aim of this study was to identify compounds that induce adipocyte browning and elucidate their mechanism of action. Among the 500 natural compounds screened, a small molecule named Rutaecarpine, was identified as a positive regulator of adipocyte browning both in vitro and in vivo. KEGG pathway analysis from RNA-seq data suggested that the AMPK signaling pathway was regulated by Rutaecarpine, which was validated by Western blot analysis. Furthermore, inhibition of AMPK signaling mitigated the browning effect of Rutaecaripine. The effect of Rutaecaripine on adipocyte browning was also abolished upon deletion of Prdm16, a downstream target of AMPK pathway. In collusion, Rutaecarpine is a potent chemical agent to induce adipocyte browning and may serve as a potential drug candidate to treat obesity.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos Bege/efeitos dos fármacos , Adipócitos Bege/metabolismo , Adipócitos Brancos/efeitos dos fármacos , Adipócitos Brancos/metabolismo , Proteínas de Ligação a DNA/metabolismo , Alcaloides Indólicos/farmacologia , Quinazolinas/farmacologia , Fatores de Transcrição/metabolismo , Adipócitos Bege/citologia , Adipócitos Brancos/citologia , Animais , Produtos Biológicos/farmacologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Técnicas In Vitro , Masculino , Camundongos , Camundongos Transgênicos , Modelos Biológicos , Obesidade/tratamento farmacológico , Obesidade/genética , Obesidade/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Termogênese/efeitos dos fármacos , Termogênese/genética , Termogênese/fisiologia
17.
Environ Sci Pollut Res Int ; 28(20): 25400-25418, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33459988

RESUMO

The current agricultural system in China highly depends on chemical fertilizers and pesticides. Consequently, agricultural production activities cause various environmental issues. Carrying out safe production provides vital support for sustainable development of agriculture, which may improve this situation. The past decades have witnessed the fast development of rural cooperatives organization in China. Given the fact that rural cooperative organization plays a crucial role in agricultural production, however, there is little empirical evidence on the relationship between cooperative membership and safe production of smallholders in China. This study aims to investigate whether the participation in farmer cooperatives contributes to safe production in agriculture in China. Using survey data covering 623 rice-producing farm households in Sichuan province in China, this study employs the endogenous switching regression model to examine the effects of the participation in farmer cooperatives on safe production in rice agriculture. The results show that cooperative membership has significantly positive effects on safe production in rice agriculture. In particular, the average treatment effects demonstrate that without the participation in cooperatives, the members' adoption of the green control techniques would reduce by 74.491%, the application of artificial weeding would reduce by 38.768%, and organic fertilizer input would reduce by 23.448%. Furthermore, the marginal treatment effect is employed to evaluate the heterogeneous effects of the participation in farmer cooperatives on safe production in rice agriculture. Heterogeneous effect analyses suggest that farmers who are more likely to participate in farmer cooperatives are easier to adopt green control technology, while farmers who are less likely to participate in farmer cooperatives are easier to adopt artificial weeding and increase organic fertilizer input. To improve safe production in rice agriculture, the Chinese government is expected to encourage rice farmers to participate in rural cooperative organizations, and to stimulate rice farmers to take collective action to address environment issues arising from agricultural production.


Assuntos
Fazendeiros , Oryza , Agricultura , China , Fertilizantes , Humanos
18.
J Clin Lipidol ; 15(1): 116-123, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33414089

RESUMO

BACKGROUND: CYP27A1 is the disease-causing gene of cerebrotendinous xanthomatosis (CTX). As a treatable lipid storage disease, early treatment can improve the prognosis. However, CTX patients reported in the literature are mostly adult patients; the phenotype spectrum of CTX in the infantile population remains elusive. OBJECTIVE: We aimed to investigate the phenotype spectrum of infants who carried pathogenic or likely pathogenic variants in the CYP27A1 gene and were suspected of having CTX. METHODS: From June 2014 to May 2020, infants with pathogenic or likely pathogenic variants in CYP27A1 gene were enrolled, who underwent next-generation sequencing or Sanger sequencing in Children's Hospital of Fudan University. Patient characteristics, clinical treatments and outcomes were extracted from electronic medical records. RESULTS: A total of 17 patients with an average onset age of 8 (1-42) days were found. The average diagnosis age was ten months. Cholestasis was the dominant symptom of these infants. Thirteen variants were detected, of which c.379C > T was a hotspot variant (26.5% alleles, 9/34). Cholestatic CTX is usually underestimated, but it could be severe or even fatal in infancy. For outcomes, 5 suffered from liver failure (36%, 5/14), 1 still showed cholestasis (7%, 1/14), 7 were asymptomatic (50%, 7/14), and 1 presented seizure and developmental delay in later childhood (7%, 1/14). CONCLUSION: Based on this infantile cohort, we concluded that it is necessary to consider the possibility of CTX caused by CYP27A1 gene variants for infants with cholestasis.


Assuntos
Xantomatose Cerebrotendinosa , Criança , Colestanotriol 26-Mono-Oxigenase , Humanos , Lactente , Masculino
19.
Cardiovasc Diabetol ; 20(1): 25, 2021 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-33494751

RESUMO

BACKGROUND: Although the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on cardiovascular events have been reported in patients with type 2 diabetes mellitus (T2DM) with or without heart failure (HF), the impact of SGLT2i on cardiac remodelling remains to be established. METHODS: We searched the PubMed, Embase, Cochrane Library and Web of Science databases up to November 16th, 2020, for randomized controlled trials reporting the effects of SGLT2i on parameters of cardiac structure, cardiac function, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level or the Kansas City Cardiomyopathy Questionnaire (KCCQ) score in T2DM patients with or without chronic HF. The effect size was expressed as the mean difference (MD) or standardized mean difference (SMD) and its 95% confidence interval (CI). Subgroup analyses were performed based on the stage A-B or stage C HF population and HF types. RESULTS: Compared to placebo or other antidiabetic drugs, SGLT2i showed no significant effects on left ventricular mass index, left ventricular end diastolic volume index, left ventricular end systolic volume index, or left atrial volume index. SGLT2i improved left ventricular ejection fraction only in the subgroup of HF patients with reduced ejection fraction (MD 3.16%, 95% CI 0.11 to 6.22, p = 0.04; I2 = 0%), and did not affect the global longitudinal strain in the overall analysis including stage A-B HF patients. SGLT2i showed benefits in the E/e' ratio (MD - 0.45, 95% CI - 0.88 to - 0.03, p = 0.04; I2 = 0%), plasma NT-proBNP level (SMD - 0.09, 95% CI - 0.16 to - 0.03, p = 0.004; I2 = 0%), and the KCCQ score (SMD 3.12, 95% CI 0.76 to 5.47, p  = 0.01; I2 = 0%) in the overall population. CONCLUSION: The use of SGLT2i was associated with significant improvements in cardiac diastolic function, plasma NT-proBNP level, and the KCCQ score in T2DM patients with or without chronic HF, but did not significantly affect cardiac structural parameters indexed by body surface area. The LVEF level was improved only in HF patients with reduced ejection fraction.


Assuntos
Função do Átrio Esquerdo/efeitos dos fármacos , Remodelamento Atrial/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Idoso , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Doença Crônica , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Recuperação de Função Fisiológica , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Volume Sistólico/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento
20.
Front Oncol ; 10: 545892, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33330024

RESUMO

Background: As an emerging clinical problem, locally advanced drug-resistant gastrointestinal stromal tumors (LADRGISTs) has relatively few therapeutic schemes. Although radiotherapy is not often considered for GISTs, it could be a valuable contributing modality. The aim of our study is to explore a safe and effective radiation regimen for LADR-GISTs. Methods: Three patients with LADR-GISTs were treated with simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) plans. In the SIB-IMRT plans, gross target volume (GTV) was divided into GTV-outer, GTV-mid, and GTV-center. And the prescribed dose of planning gross target volume (PGTV) and GTV-outer were both set to 50.4 Gy in 28 fractions. GTV-mid and GTV-center were simultaneously boosted to 60-62 Gy and 62-64 Gy respectively. For comparison purposes, conventional IMRT (Con-IMRT) plans with uniform dose distribution were generated for same optimization objectives without a dose boost to GTV-mid and GTV-center. All plans were optimized to make sure that deliver at least 95% of the prescription dose was delivered to PGTV. Isodose distribution, dose profiles, conformity indexes (CIs), monitor units (MUs), and dose volume histogram (DVH) was evaluated for each individual patient. After the three patients were treated with SIB-IMRT plans, the relative changes in the tumor size and CT values by CT scanning were also tracked. Results: Compared with Con-IMRT plans, SIB-IMRT plans saw a significant increase from D95 to D2 of the GTV. With steeper dose gradients in the dose profiles, SIB-IMRT plans had GTV-mid and GTV-center accumulated with higher dose mainly by delivering extra 93 MUs in average. However, there was no significant difference in CIs and organs at risks (OARs) DVH. The relative changes in tumor size and CT values of the three patients in follow up were up to the Choi criteria and the three patients were all assessed as partial response. Conclusions: The proposed SIB-IMRT may be a potential technique for achieving objective response and prolonging survival of selected GISTs patients.

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