RESUMO
CREB-regulated transcription coactivator 1 (CRTC1), a pivotal synaptonuclear messenger, regulates synaptic plasticity and transmission to prevent depression. Despite exhaustive investigations into CRTC1 mRNA reductions in the depressed mice, the regulatory mechanisms governing its transcription remain elusive. Consequently, exploring rapid but non-toxic CRTC1 inducers at the transcriptional level is important for resisting depression. Here, we demonstrate the potential of D-arabinose, a unique monosaccharide prevalent in edible-medicinal plants, to rapidly enter the brain and induce CRTC1 expression, thereby eliciting rapid-acting and persistent antidepressant responses in chronic restrain stress (CRS)-induced depressed mice. Mechanistically, D-arabinose induces the expressions of peroxisome proliferator-activated receptor gamma (PPARγ) and transcription factor EB (TFEB), thereby activating CRTC1 transcription. Notably, we elucidate the pivotal role of the acetyl-CoA synthetase short-chain family member 2 (ACSS2) as an obligatory mediator for PPARγ and TFEB to potentiate CRTC1 transcription. Furthermore, D-arabinose augments ACSS2-dependent CRTC1 transcription by activating AMPK through lysosomal AXIN-LKB1 pathway. Correspondingly, the hippocampal down-regulations of ACSS2, PPARγ or TFEB alone failed to reverse CRTC1 reductions in CRS-exposure mice, ultimately abolishing the anti-depressant efficacy of D-arabinose. In summary, our study unveils a previously unexplored role of D-arabinose in activating the ACSS2-PPARγ/TFEB-CRTC1 axis, presenting it as a promising avenue for the prevention and treatment of depression.
Assuntos
Arabinose , PPAR gama , Camundongos , Animais , PPAR gama/genética , PPAR gama/metabolismo , Arabinose/farmacologia , Arabinose/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Encéfalo/metabolismoRESUMO
PURPOSE: Bloodstream infection (BSI) caused by Carbapenem-Resistant Enterobacteriaceae (CRE) are associated with poor outcomes in hematological patients. The aim of this study was to identify risk factors for mortality and evaluate the value of epidemiological feature of carbapenemases in guiding antimicrobial treatment options. METHODS: Hematological patients with monomicrobial CRE BSI between January 2012 and April 2021 were included. The primary outcome was all-cause mortality 30 days after BSI onset. RESULTS: A total of 94 patients were documented in the study period. Escherichia coli was the most common Enterobacteriaceae, followed by Klebsiella pneumoniae. 66 CRE strains were tested for carbapenemase genes, and 81.8% (54/66) were positive, including NDM (36/54), KPC (16/54), IMP (1/54). Besides, one E. coli isolate was found to express both NDM and OXA-48-like genes. Overall, 28 patients received an antimicrobial treatment containing ceftazidime-avibactam (CAZ-AVI), of which 21 cases were combined with aztreonam. The remaining 66 patients were treated with other active antibiotics (OAAs). The 30-day mortality rate was 28.7% (27/94) for all patients, and was only 7.1% ((2/28) for patients treated with CAZ-AVI. In multivariate analysis, the presence of septic shock at BSI onset (OR 10.526, 95% CI 1.376-76.923) and pulmonary infection (OR 6.289, 95% CI 1.351-29.412) were independently risk factors for 30-day mortality. Comparing different antimicrobial regimens, CAZ-AVI showed a significant survive benefit than OAAs (OR 0.068, 95% CI 0.007-0.651). CONCLUSION: CAZ-AVI-containing regimen is superior to OAAs for CRE BSI. As the predominance of blaNDM in our center, we recommend the combination with aztreonam when choose CAZ-AVI.
Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Enterobacteriaceae , Sepse , Humanos , Aztreonam , Escherichia coli/genética , Ceftazidima , Antibacterianos/uso terapêutico , Klebsiella pneumoniae/genética , Infecções por Enterobacteriaceae/tratamento farmacológico , Combinação de Medicamentos , Sepse/tratamento farmacológico , Fatores de Risco , Testes de Sensibilidade MicrobianaRESUMO
INTRODUCTION: Obesity causes many life-threatening diseases. It is important to develop effective approaches for obesity treatment. Oral supplementation with spermidine retards age-related processes, but its influences on obesity and various metabolic tissues remain largely unknow. This study aims to investigate the effects of oral spermidine on brown adipose tissue (BAT) and skeletal muscle as well as its roles in counteracting obesity and metabolic disorders. METHODS AND RESULTS: Spermidine is orally administrated into high-fat diet (HFD)-fed mice. The weight gain, insulin resistance, and hepatic steatosis are attenuated by oral spermidine in HFD-fed mice, accompanied by an alleviation of white adipose tissue inflammation. Oral spermidine promotes BAT activation and metabolic adaptation of skeletal muscle in HFD-fed mice, evidenced by UCP-1 induction and CREB activation in both tissues. Notably, oral spermidine upregulates tyrosine hydroxylase in hypothalamus of HFD-fed mice; spermidine treatment increases tyrosine hydroxylase expression and norepinephrine production in neurocytes, which leads to CREB activation and UCP-1 induction in brown adipocytes and myotubes. Spermidine also directly promotes UCP-1 and PGC-1α expression in brown adipocytes and myotubes. CONCLUSION: Spermidine serves as an oral supplement to attenuate obesity and metabolic disorders through hypothalamus-dependent or -independent BAT activation and skeletal muscle adaptation.
Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Obesidade/tratamento farmacológico , Espermidina/administração & dosagem , Espermidina/farmacologia , Tecido Adiposo Marrom/citologia , Tecido Adiposo Marrom/metabolismo , Administração Oral , Animais , Dieta Hiperlipídica/efeitos adversos , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Resistência à Insulina , Masculino , Camundongos Endogâmicos C57BL , Fibras Musculares Esqueléticas/efeitos dos fármacos , Músculo Esquelético/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Obesidade/etiologia , Paniculite/tratamento farmacológico , Paniculite/etiologia , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
The objective of this bibliometric review was to identify the volume, breadth, and characteristics of clinical studies evaluating Tai Chi published between January 2010 and January 2020. Five English and four Chinese language databases were searched. Following independent screening, 1018 eligible publications representing 987 studies were identified, which was a three-fold increase from the previous decade. Most common were randomized controlled trials (548/987, 55.5 %), followed by systematic reviews (157/987, 15.9 %), non-randomized controlled clinical studies (152/987, 15.4 %), case series (127/987, 12.9 %) and case reports (3/987, 0.3 %) that were conducted in China (730/987, 74.0 %), followed by the United States of America (123/987, 12.5 %) and South Korea (20/987, 2.0 %). Study participants were mostly in the adult (55.2 %) and/or older adult (72.0 %) age groups. The top ten diseases/conditions were hypertension, chronic obstructive pulmonary disease, diabetes, knee osteoarthritis, heart failure, depression, osteoporosis/osteopenia, breast cancer, coronary heart disease and insomnia. A quarter of the studies enrolled healthy participants to evaluate the effects of Tai Chi on health promotion/preservation, balance/falls, and physiological/biomechanical outcomes. Yang style Tai Chi was the most popular, followed by Chen and Sun style. Tai Chi was mostly commonly delivered face-to-face by a Tai Chi instructor in group settings for 60 min, three times a week, for 12 weeks. Most studies (93.8 %) reported at least one outcome in favor of Tai Chi. Adverse events were underreported (7.2 %). Over half fell short of expected intervention reporting standards, signalling the need for Tai Chi extensions to existing guidelines.
Assuntos
Osteoartrite do Joelho , Doença Pulmonar Obstrutiva Crônica , Tai Chi Chuan , Acidentes por Quedas , Idoso , Bibliometria , HumanosRESUMO
Sargassum seaweeds produce abundant biomass in China and have long been used as herbal medicine and food. Their characteristic fatty acid (FA) profiles and related potential function in promoting cardiovascular health (CVH) have not been systematically investigated. In this study, FA profiles of four medicinal Sargassum were characterized using GC-MS. Principal component analysis was used to discriminate the four medicinal Sargassum, and orthogonal projection to latent structures discriminant analysis was carried out between the two official species HAI ZAO and between the two folk medicine species HAI QIAN. In all of the algae investigated, the major SFA and MUFA were palmitic and stearic acid, respectively, while the major PUFAs were linoleic, arachidonic, and eicosapentaenoic acid. S. fusiforme and S. horneri had higher concentrations of PUFAs. With respect to CVH, all of the studied species, particularly S. fusiforme, exhibited satisfactory levels such as PUFA/SFA ratio and n-6/n-3 ratio. Each species possesses a unique FA profile and is discriminated clearly. Potential key FA markers (between the two Chinese official species, and between the two folk species) are assessed. The study provides characteristic fatty acid profiles of four Chinese medicinal Sargassum and their related potential function in promoting CVH.