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1.
Int Urol Nephrol ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34783980

RESUMO

PURPOSE: To evaluate the effects of manganese superoxide dismutase (Mn-SOD) from thermophilic bacterium HB27 (name as Tt-SOD) on chemical cystitis. METHODS: Control and experimental rats were infused by intravesical saline or hydrochloric acid (HCl) on the first day of the experiments. Saline, sodium hyaluronate (SH) or Tt-SOD were infused intravesically once a day for three consequent days. On the fifth day, the rats were weighted and sacrificed following a pain threshold test. The bladder was harvested for histological and biochemical analyses. RESULTS: Tt-SOD could reduce the bladder index, infiltration of inflammatory cells in tissues, serum inflammatory factors and SOD levels, mRNA expression of inflammatory factors in tissues, and increase perineal mechanical pain threshold and serum MDA and ROS levels in HCl-induced chemical cystitis. Furthermore, Tt-SOD alleviated inflammation and oxidative stress by the negative regulation of the NF-κB p65 and p38 MAPK signaling pathway. CONCLUSIONS: Intravesical instillation of Tt-SOD provides protective effects against HCl-induced cystitis.

2.
J Alzheimers Dis ; 84(1): 129-140, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34487044

RESUMO

BACKGROUND: Abnormal morphology and function of neurons in the prefrontal cortex (PFC) are associated with cognitive deficits in rodent models of Alzheimer's disease (AD), particularly in cortical layer-5 pyramidal neurons that integrate inputs from different sources and project outputs to cortical or subcortical structures. Pyramidal neurons in layer-5 of the PFC can be classified as two subtypes depending on the inducibility of prominent hyperpolarization-activated cation currents (h-current). However, the differences in the neurophysiological alterations between these two subtypes in rodent models of AD remain poorly understood. OBJECTIVE: To investigate the neurophysiological alterations between two subtypes of pyramidal neurons in hAPP-J20 mice, a transgenic model for early onset AD. METHODS: The synaptic transmission and intrinsic excitability of pyramidal neurons were investigated using whole-cell patch recordings. The morphological complexity of pyramidal neurons was detected by biocytin labelling and subsequent Sholl analysis. RESULTS: We found reduced synaptic transmission and intrinsic excitability of the prominent h-current (PH) cells but not the non-PH cells in hAPP-J20 mice. Furthermore, the function of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels which mediated h-current was disrupted in the PH cells of hAPP-J20 mice. Sholl analysis revealed that PH cells had less dendritic intersections in hAPP-J20 mice comparing to control mice, implying that a lower morphological complexity might contribute to the reduced neuronal activity. CONCLUSION: These results suggest that the PH cells in the medial PFC may be more vulnerable to degeneration in hAPP-J20 mice and play a sustainable role in frontal dysfunction in AD.

3.
Commun Biol ; 4(1): 982, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34408242

RESUMO

The position of abdominal organs, and mechanisms by which these are centrally connected, are currently described in peritoneal terms. As part of the peritoneal model of abdominal anatomy, there are multiple mesenteries. Recent findings point to an alternative model in which digestive organs are connected to a single mesentery. Given that direct evidence of this is currently lacking, we investigated the development and shape of the entire mesentery. Here we confirm that, within the abdomen, there is one mesentery in which all abdominal digestive organs develop and remain connected to. We show that all abdominopelvic organs are organised into two, discrete anatomical domains, the mesenteric and non-mesenteric domain. A similar organisation occurs across a range of animal species. The findings clarify the anatomical foundation of the abdomen; at the foundation level, the abdomen comprises a visceral (i.e. mesenteric) and somatic (i.e. musculoskeletal) frame. The organisation at that level is a fundamental order that explains the positional anatomy of all abdominopelvic organs, vasculature and peritoneum. Collectively, the findings provide a novel start point from which to systemically characterise the abdomen and its contents.

4.
J Diabetes Res ; 2021: 6692695, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34046504

RESUMO

Gestational diabetes mellitus (GDM) is a major public health issue, and the aim of the present study was to identify the factors associated with GDM. Databases were searched for observational studies until August 20, 2020. Pooled odds ratios (ORs) were calculated using fixed- or random-effects models. 103 studies involving 1,826,454 pregnant women were identified. Results indicated that maternal age ≥ 25 years (OR: 2.466, 95% CI: (2.121, 2.866)), prepregnancy overweight or obese (OR: 2.637, 95% CI: (1.561, 4.453)), family history of diabetes (FHD) (OR: 2.326, 95% CI: (1.904, 2.843)), history of GDM (OR: 21.137, 95% CI: (8.785, 50.858)), macrosomia (OR: 2.539, 95% CI: (1.612, 4.000)), stillbirth (OR: 2.341, 95% CI: (1.435, 3.819)), premature delivery (OR: 3.013, 95% CI: (1.569, 5.787)), and pregestational smoking (OR: 2.322, 95% CI: (1.359, 3.967)) increased the risk of GDM with all P < 0.05, whereas history of congenital anomaly and abortion, and HIV status showed no correlation with GDM (P > 0.05). Being primigravida (OR: 0.752, 95% CI: (0.698, 0.810), P < 0.001) reduced the risk of GDM. The factors influencing GDM included maternal age ≥ 25, prepregnancy overweight or obese, FHD, history of GDM, macrosomia, stillbirth, premature delivery, pregestational smoking, and primigravida.

5.
Zhongguo Zhong Yao Za Zhi ; 46(1): 171-176, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33645067

RESUMO

The aim of this paper was to study the effect and mechanism of fucoxanthin on insulin resistance of obese mice induced by high-fat diet. Fifty C57 BL/6 J male mice were randomly divided into control group and high-fat diet group. The insulin resistance model was induced with high-fat diet for 12 weeks, and model mice were randomly divided into model group, fucoxanthin-0.2% group, fucoxanthin-0.4% group and metformin group. After dietary treatment for 6 weeks, the body weight and epididymal fat weight in each group were measured. Fasting blood glucose(FBG), fasting insulin(FINS), total cholesterol(TC), triglyceride(TG), low-density lipoprotein(LDL-C) and high-density lipoprotein(HDL-C) were measured, and insulin resistance index(HOMA-IR) was calcula-ted. The pathological morphology in liver was observed by hematoxylin eosin staining, and the expressions of some key proteins in insulin receptor substrate 1(IRS-1)/posphoinositide 3-kinase(PI3 K)/serine-threonine kinase(Akt) and peroxisome proliferators-activated receptor-γ(PPARγ)/sterol regulatory element binding protein-1(SREBP-1)/fatty acid synthetase(FAS) pathways in liver were detected by Western blot. According to the findings, compared with the model group, levels of body weight, epididymal fat weight, FBG, FINS, TC, TG, LDL-C and HOMA-IR, as well as protein expressions of PPARγ, SREBP-1 and FAS in liver were significantly reduced(P<0.05 or P<0.01), while level of HDL-C and protein expressions of p-IRS-1, IRS-1, PI3 K and p-Akt in liver were signi-ficantly increased after treatment with fucoxanthin(P<0.05 or P<0.01). And the pathological changes of liver tissue in fucoxanthin-treated mice were also improved obviously. The results showed that fucoxanthin could improve obesity, hyperglycemia and hyperlipidemia, and alleviate insulin resistance in obese mice, and its mechanism is possibly related to the regulation of IRS-1/PI3 K/Akt and PPARγ/SREBP-1/FAS pathways.


Assuntos
Resistência à Insulina , Animais , Dieta Hiperlipídica/efeitos adversos , Insulina , Fígado , Masculino , Camundongos , Camundongos Obesos , Xantofilas
6.
Neuropsychopharmacology ; 46(5): 970-981, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33514875

RESUMO

Impaired glutamate homeostasis is a key characteristic of the neurobiology of drug addiction in rodent models and contributes to the vulnerability to relapse to drug seeking. Although disrupted astrocytic and presynaptic regulation of glutamate release has been considered to constitute with impaired glutamate homeostasis in rodent model of drug relapse, the involvement of endocannabinoids (eCBs) in this neurobiological process has remained largely unknown. Here, using cocaine self-administration in rats, we investigated the role of endocannabinoids in impaired glutamate homeostasis in the core of nucleus accumbens (NAcore), which was indicated by augmentation of spontaneous synaptic glutamate release, downregulation of metabotropic glutamate receptor 2/3 (mGluR2/3), and mGluR5-mediated astrocytic glutamate release. We found that the endocannabinoid, anandamide (AEA), rather than 2-arachidonoylglycerol elicited glutamate release through presynaptic transient receptor potential vanilloid 1 (TRPV1) and astrocytic cannabinoid type-1 receptors (CB1Rs) in the NAcore of saline-yoked rats. In rats with a history of cocaine self-administration and extinction training, AEA failed to alter synaptic glutamate release in the NAcore, whereas CB1R-mediated astrocytic glutamate release by AEA remained functional. In order to induce increased astrocytic glutamate release via exogenous AEA, (R)-methanandamide (methAEA, a metabolically stable form of AEA) was chronically infused in the NAcore via osmotic pumps during extinction training. Restoration of mGluR2/3 function and mGluR5-mediated astrocytic glutamate release was observed after chronic methAEA infusion. Additionally, priming or cue-induced reinstatement of cocaine seeking was inhibited in methAEA-infused rats. These results demonstrate that enhancing endocannabinoid signaling is a potential pathway to restore glutamate homeostasis and may represent a promising therapeutic strategy for preventing cocaine relapse.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Preparações Farmacêuticas , Animais , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Endocanabinoides , Extinção Psicológica , Ácido Glutâmico , Homeostase , Núcleo Accumbens , Ratos , Ratos Sprague-Dawley , Recidiva , Autoadministração
7.
Pharmacol Biochem Behav ; 202: 173103, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33444600

RESUMO

Neurodevelopmental abnormalities are associated with cognitive dysfunction in schizophrenia. In particular, deficits of working memory, are consistently observed in schizophrenia, reflecting prefrontal cortex (PFc) dysfunction. To elucidate the mechanism of such deficits in working memory, the pathophysiological properties of PFc neurons and synaptic transmission have been studied in several developmental models of schizophrenia. Given the pathogenetic heterogeneity of schizophrenia, comparison of PFc synaptic transmission between models of prenatal and postnatal defect would promote our understanding on the developmental components of the biological vulnerability to schizophrenia. In the present study, we investigated the excitatory synaptic transmission onto pyramidal cells localized in layer 5 of the medial PFc (mPFc) in two developmental models of schizophrenia: gestational methylazoxymethanol acetate (MAM) administration and post-weaning social isolation (SI). We found that both models exhibited defective spatial working memory, as indicated by lower spontaneous alternations in a Y-maze paradigm. The recordings from pyramidal neurons in both models exhibited decreased spontaneous excitatory postsynaptic current (sEPSC), representing the reduction of excitatory synaptic transmission in the mPFc. Interestingly, a positive correlation between the impaired spontaneous alternation behavior and the decreased excitatory synaptic transmission of pyramidal neurons was found in both models. These findings suggest that diminished excitatory neurotransmission in the mPFc could be a common pathophysiology regardless of the prenatal and postnatal pathogenesis in developmental models of schizophrenia, and that it might underlie the mechanism of defective working memory in those models.


Assuntos
Memória de Curto Prazo , Transtornos do Neurodesenvolvimento/psicologia , Esquizofrenia/metabolismo , Psicologia do Esquizofrênico , Memória Espacial , Transmissão Sináptica , Animais , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Feminino , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Acetato de Metilazoximetanol/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia , Gravidez , Células Piramidais/metabolismo , Células Piramidais/patologia , Esquizofrenia/induzido quimicamente , Isolamento Social , Memória Espacial/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos
8.
Ying Yong Sheng Tai Xue Bao ; 32(1): 182-190, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33477226

RESUMO

The climate change caused by elevated CO2 concentration and drought are bound to affect the growth of soybean. Few studies have addressed the effects of elevated CO2 concentration on the physiology and biochemistry of soybean under drought stress. Here, we examined the changes of photosynthetic ability, photosynthetic pigment accumulation, antioxidant level, osmotic adjustment substances, hormone levels, signal transduction enzymes and gene expression level of soybean at flowering stage under different CO2 concentration (400 and 600 µmol·mol-1) and drought stress (normal water: leaf relative water content was 83%-90%; drought stress: leaf relative water content was 64%-70%). The results showed that the transpiration rate, water use efficiency and net photosynthetic rate of soybean leaves were significantly increased by elevated CO2 concentration, but the content of chlorophyll b was decreased under drought stress. Elevated CO2 concentration significantly increased peroxidase activity and abscisic acid content of leaves under drought stress, decreased the content of proline, and did not affect the content of soluble saccharides. The increased CO2 concentration under drought stress significantly promoted the content of calcium-dependent protein kinase and glutathione-S-transferase, and up-regulated the expression of related genes, while significantly decreased the content of mitogen-activated protein kinase and the heat shock protein, and down-regulated the expression of their genes. The results would be helpful to understand the impacts of climate change on the growth, physiology and biochemistry of soybean, and to deal with the production problems of soybean under future climate change.


Assuntos
Secas , Soja , Dióxido de Carbono , Fotossíntese , Folhas de Planta , Água
9.
Am J Nephrol ; 51(11): 907-918, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33152735

RESUMO

BACKGROUND: Kidney fibrosis is the ultimate consequence of advanced stages of chronic kidney disease (CKD); however, there are currently no reliable biomarkers or noninvasive diagnostic tests available for the detection of kidney fibrosis. Lysyl oxidase (LOX) promotes collagen cross-linking, and serum LOX levels have been shown to be elevated in patients with fibrosis of the heart, lungs, and liver. However, serum LOX levels have not been reported in patients with kidney fibrosis. We explored whether serum LOX levels are associated with kidney fibrosis. METHOD: Overall, 202 patients with kidney disease underwent renal biopsy, scoring of kidney fibrosis, and determination of the area of kidney fibrosis. LOX levels were measured in serum and in kidney tissues. We analyzed the association of circulating LOX and tissue LOX levels with the scores and areas of kidney fibrosis. LOX expression was also investigated with in vitro and in vivo kidney fibrosis models. RESULTS: Serum LOX levels were higher in patients with kidney fibrosis than in those without kidney fibrosis (p < 0.001) and higher in patients with moderate-severe kidney fibrosis than in patients with mild kidney fibrosis (p < 0.001). Both serum LOX and renal tissue LOX levels correlated with the area of kidney fibrosis (r = 0.748, p < 0.001; r = 0.899, p < 0.001, respectively). Receiver operating characteristic curve analysis of serum LOX levels showed an area under the curve of 0.80 (95% CI: 0.74-0.86). The optimal serum LOX level cutoff point was 253.34 pg/mL for the prediction of kidney fibrosis and 306.56 pg/mL for the prediction of moderate-severe kidney fibrosis. LOX expression levels were significantly upregulated (2.3-2.6 and 6-fold, respectively) in in vitro and in vivo interstitial fibrosis models. CONCLUSIONS: Both serum LOX and tissue LOX levels correlated with the presence and degree of kidney fibrosis in patients with CKD. These results suggest that serum LOX levels could potentially serve as a noninvasive diagnostic biomarker for kidney fibrosis and may further potentially serve as a stratified biomarker for the identification of mild and moderate-severe kidney fibrosis.


Assuntos
Rim/patologia , Proteína-Lisina 6-Oxidase/sangue , Insuficiência Renal Crônica/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biópsia , Estudos de Casos e Controles , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Valores de Referência , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/patologia , Índice de Gravidade de Doença , Adulto Jovem
10.
BMC Med Educ ; 20(1): 323, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32962664

RESUMO

BACKGROUND: Anxiety and depression have been increasing among Chinese medical students. The psychological well-being of Chinese medical students has become a critical focus of attention for the medical education community. Increasing evidence shows that positive psychology interventions can be effective in the enhancement of psychological well-being, and may help to prevent depressive symptoms in university students. In the present study, we aimed to explore the potential effect of positive psychology education on improving the mental health of Chinese medical students. METHODS: An 8-week classroom-based positive psychology intervention workshop, which was established as an elective course embedded in the regular school curriculum, was conducted at the School of Medicine, South China University of Technology (SCUT), China. Undergraduate medical students of the institute in year-2 or year-3 of academic study participated in this training course voluntarily. The participants' self-reported data on the hope scale, life satisfaction scale, subjective happiness scale, and depression and anxiety scale were collected and analyzed at pre-course (n = 61) and post-course (n = 49) times. The investigation was also validated with an independent cohort of students who enrolled in the course in the year following the preliminary study. RESULTS: The analyses showed that the psychological well-being of the participants were improved after the intervention. Their mean scores on the hope scale, life satisfaction scale and subjective happiness scale were significantly improved (P < 0.05), while their symptom levels of depression and anxiety were significantly reduced (P < 0.01). A similar trend was observed in the validation cohort. CONCLUSIONS: These preliminary findings suggest that positive psychology education holds promise for improving psychological well-being among Chinese medical students. Further investigations with larger and well-controlled sample cohorts may yield more convincing and reliable results.


Assuntos
Estudantes de Medicina , China , Humanos , Projetos Piloto , Psicologia Positiva , Estresse Psicológico
11.
J Diabetes Res ; 2020: 7574245, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32851097

RESUMO

The proliferation of vascular smooth muscle cells (VSMCs) induced by oxidative injury is one of the main features in diabetes-accelerated atherosclerosis. Geranylgeranyl transferase-I (GGTase-I) is an essential enzyme mediating posttranslational modification, especially the geranylgeranylation of small GTPase, Rac1. Our previous studies found that GGTase-I played an important role in diabetes-accelerated atherosclerosis. However, its exact role is largely unclear. In this study, mouse conditional knockout of VSMC GGTase-I (Pggt1b Δ/Δ mice) was generated using the CRISPR/Cas9 system. The mouse model of diabetes-accelerated atherosclerosis was induced by streptozotocin injections and an atherogenic diet. We found that GGTase-I knockout attenuated diabetes-accelerated atherosclerosis in vivo and suppressed high-glucose-induced VSMC proliferation in vitro. Moreover, after a 16-week duration of diabetes, Pggt1b Δ/Δ mice exhibited lower α-smooth muscle actin (α-SMA) and nitrotyrosine level, Rac1 activity, p47phox and NOXO1 expression, and phospho-ERK1/2 and phosphor-JNK content than wild-type mice. Meanwhile, the same changes were found in Pggt1b Δ/Δ VSMCs cultured with high glucose (22.2 mM) in vitro. In conclusion, GGTase-I knockout efficiently blocked diabetes-accelerated atherosclerosis, and this protective effect must be related to the inhibition of VSMC proliferation. The potential mechanisms probably involved interfering Rac1 geranylgeranylation, inhibiting the assembly of NADPH oxidase cytosolic regulatory subunits, reducing oxidative injury, and decreasing ERK1/2 and JNK phosphorylation.


Assuntos
Alquil e Aril Transferases/genética , Aterosclerose/genética , Diabetes Mellitus Experimental/genética , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Estresse Oxidativo/genética , Alquil e Aril Transferases/metabolismo , Animais , Aterosclerose/metabolismo , Aterosclerose/patologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Camundongos , Camundongos Knockout , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Fosforilação , Transdução de Sinais/genética
12.
Neuropharmacology ; 177: 108231, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32693006

RESUMO

Juvenile social isolation (SI) and neglect have a negative impact on neurodevelopment persistently, which is associated with cognitive dysfunction in neurodevelopmental disorders. Given the critical role of metabotropic glutamate receptors (mGluRs) in synaptic homeostasis of the prefrontal cortex (PFC), pharmacological intervention on mGluRs has been attempted in order to improve cognitive dysfunction in animal models of neurodevelopmental disorder, as well as in clinical trials. Here we examined the effects of the mGluR2/3 antagonist LY341495 on prefrontal synaptic transmission, spatial working memory, and recognition memory in adult C57BL/6J mice that experienced juvenile SI. We found that SI-reared mice exhibited working memory impairment and decreased excitatory presynaptic release probability of pyramidal neurons in the medial PFC compared with group-reared mice. The positive effect of LY341495 on excitatory synaptic transmission in SI-reared mice was more prominent than the effect in group-reared mice. A single treatment with mGluR2/3 antagonist LY341495 significantly improved the performance of SI-reared mice in the Y-maze test but not in the novel object recognition (NOR) test, while repeated treatments were effective in both tasks. These findings suggest that enhancing glutamatergic transmission via inhibition of mGluR2/3 signaling might represent a promising strategy for improving cognitive function in neurodevelopmental disorders.


Assuntos
Aminoácidos/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Memória de Curto Prazo/efeitos dos fármacos , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Isolamento Social/psicologia , Xantenos/farmacologia , Fatores Etários , Animais , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memória de Curto Prazo/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Glutamato Metabotrópico/metabolismo
13.
Chin Med J (Engl) ; 133(12): 1390-1396, 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32251003

RESUMO

BACKGROUND: Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients. METHODS: From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores. RESULTS: Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation. CONCLUSIONS: LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Transplante de Pulmão/métodos , Pneumonia Viral/complicações , Fibrose Pulmonar/cirurgia , Síndrome do Desconforto Respiratório/cirurgia , Idoso , COVID-19 , Infecções por Coronavirus/mortalidade , Oxigenação por Membrana Extracorpórea , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Fibrose Pulmonar/mortalidade , Síndrome do Desconforto Respiratório/mortalidade , SARS-CoV-2
14.
Cell Death Dis ; 11(3): 211, 2020 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-32235836

RESUMO

Copper ions play various roles in mammalian cells, presumably due to their involvement in different enzymatic reactions. Some studies indicated that serum copper correlates with fibrosis in organs, such as liver and lung. However, the mechanism is unknown. Here, we explored the role of copper in kidney fibrosis development and possible underlying mechanisms. We found that copper transporter 1 (CTR1) expression was increased in the kidney tissues in two fibrosis models and in patients with kidney fibrosis. Similar results were also found in renal tubular epithelial cells and fibroblast cells treated with transforming growth factor beta (TGF-ß). Mechanistically, the upregulation of CTR1 required Smads-dependent TGF-ß signaling pathway and Smad3 directly binded to the promoter of CTR1 in renal fibroblast cells using chromatin immunoprecipitation. Elevated CTR1 induced increase of copper intracellular influx. The elevated intracellular copper ions activated lysyl oxidase (LOX) to enhance the crosslinking of collagen and elastin, which then promoted kidney fibrosis. Reducing intracellular copper accumulation by knocking down CTR1 ameliorated kidney fibrosis in unilateral ureteral obstruction induced renal fibrosis model and renal fibroblast cells stimulated by TGF-ß. Treatment with copper chelator tetrathiomolybdate (TM) also alleviated renal fibrosis in vivo and in vitro. In conclusion, intracellular copper accumulation plays a unique role to kidney fibrosis by activating LOX mediated collagen and elastin crosslinking. Inhibition of intracellular copper overload may be a potential portal to alleviate kidney fibrosis.


Assuntos
Cobre/efeitos adversos , Fibrose/genética , Nefropatias/genética , Proteína-Lisina 6-Oxidase/metabolismo , Animais , Cobre/metabolismo , Humanos , Ratos , Transdução de Sinais
15.
J Adv Nurs ; 76(6): 1416-1424, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32108382

RESUMO

AIMS: To evaluate the effectiveness and safety of Xin Huang Pian skin patches for patients with acute gouty arthritis. BACKGROUND: In China, patients with acute gouty arthritis benefit from skin patcheses with herbal medicines. But the clinical effects of skin patches with Xin Huang Pian are rarely reported. DESIGN: A Randomized, Double-Blind, Active-Controlled Trial. METHODS: The trial was performed from January 2015-December 2018 at the First Affiliated Hospital of Sun Yat-sen University in China. It was conducted with one intervention group (skin patches of Xin Huang Pian, N = 30) and one active control group (skin patches of Diclofenac Diethylamine Emulgel, N = 31). Participants and study investigators were both blinded to the treatment assignments. The primary outcomes were the improvement of joints' symptoms. The secondary outcomes were changes in white blood cells, erythrocyte sedimentation rate and C-reactive protein. RESULTS: Skin patches of Xin Huang Pian showed quick effect on decreasing joint pain at 3rd day of treatment. Wherever only at 7th day, Diclofenac Diethylamine Emulgel markedly lowered joint pain. Xin Huang Pian also showed superior effect than Diclofenac Diethylamine Emulgel on improving joint swelling and range of motion and decreasing the levels of C-reactive protein and erythrocyte sedimentation rate. No adverse reactions were observed in skin patches of Xin Huang Pian treatment. CONCLUSION: Skin patches of Xin Huang Pian appeared to be safe and efficacious for relieving joint symptoms in patients with acute gouty arthritis. The mechanism might be associated with the decreased levels of C-reactive protein and erythrocyte sedimentation rate. IMPACT: Skin-patcheses with Xin Huang Pian are more effective than Diclofenac Diethylamine Emulgel on improving joint pain, swelling and range of motion. Xin Huang Pian treatment showed superior effects compared with Diclofenac Diethylamine Emulgel on decreasing levels of C-reactive protein and erythrocyte sedimentation rate. Patients with acute gouty arthritis may benefit from skin patches of Xin Huang Pian for effective relief from joint pain and swelling. Chinese Clinical Trial Registration: ChiCTR-TRC-1300 4122.


Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Artrite Gotosa/tratamento farmacológico , Diclofenaco/uso terapêutico , Dietilaminas/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Supressores da Gota/uso terapêutico , Administração Cutânea , Analgésicos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , China , Diclofenaco/administração & dosagem , Método Duplo-Cego , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Supressores da Gota/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Fitoterapia , Distribuição Aleatória
16.
J Nat Prod ; 83(2): 362-373, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32031812

RESUMO

Eight new dammarane-type triterpenoids (1-8), together with a related known analogue (9), were isolated from the roots of Rhus chinensis, a traditional Chinese medicine for treating coronary artery heart disease, guided by LC-MS analysis. Their structures were elucidated based on extensive spectroscopic analysis and quantum chemical calculations. Notably, compounds 1-7 and 9 possess an unusual 17α-side chain, and 1-4, 6, and 9 contain an uncommon 3-methyl-5,6-dihydro-2H-pyran-2-one moiety in the side chain. Compounds 1-5 and 9 have a 3,19-hemiketal bridge in the A ring. In an in vivo bioassay, 1, 2, and 4-6 exhibited significant preventive effects on zebrafish heart failure at 0.5 µg/mL, improving heart dilatation, venous congestion, cardiac output, blood flow velocity, and heart rate. Compound 5, displaying the most promising heart failure preventive activities, showed even better effects on increasing cardiac output (72%) and blood flow velocity (83%) than six first-line heart failure therapeutic drugs. Moreover, 1, 2, and 6 prevented the formation of thrombosis in zebrafish at 0.5 µg/mL. The present investigation suggests that the new dammarane triterpenoids might be partially responsible for the utility of R. chinensis in treating coronary artery heart disease.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Rhus/química , Trombose/tratamento farmacológico , Triterpenos/química , Animais , Estrutura Molecular , Raízes de Plantas/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Peixe-Zebra/fisiologia
17.
Genet Test Mol Biomarkers ; 24(1): 33-37, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31880483

RESUMO

Background: Tumor necrosis factor-alpha (TNF-α) is a major proinflammatory cytokine that has been posited to be involved in the development of chronic pancreatitis (CP). Several studies have been carried out that explored the association between the TNF-α -308A/G polymorphism and CP; however, conflicting results have emerged. The aim of this study was to perform a meta-analysis to provide a more precise assessment of the relationship between the TNF-α -308A/G polymorphism and CP risk. Methods: Case-control studies were identified using PubMed, Embase, Web of Science, Cochrane Library, and Chinese National Knowledge Infrastructure through January 2019 from which seven were identified that met all inclusion criteria. Results: This meta-analysis included 695 CP cases and 742 controls. A positive association was found between the A allele and the risk of CP using the additive model (OR [odds ratio] = 1.83, 95% CI [confidence interval] = 1.08-3.10). We also found, after excluding the Hardy-Weinberg equilibrium-violating studies, that the AA genotype was significantly associated with CP in both the additive and recessive models (OR = 2.28, 95% CI = 1.27-4.07; OR = 2.19, 95% CI = 1.26-3.81). Conclusion: This meta-analysis indicates that the A allele of the TNF-α -308A/G polymorphism increases the risk of CP.


Assuntos
Pancreatite Crônica/genética , Fator de Necrose Tumoral alfa/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença , Humanos , Masculino , Mutação , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Fator de Necrose Tumoral alfa/metabolismo
18.
Spectrochim Acta A Mol Biomol Spectrosc ; 227: 117684, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31672379

RESUMO

The probabilities of laser cooling of TeH- anion via a spin-forbidden transition and a three-electronic-level transition are proposed. The potential energy curves of the X1Σ+, a3∏, A1∏, and b3Σ+ electronic states of tellurium monohydride anion (TeH-) are calculated using multi-reference configuration interaction method. Davidson corrections, core-valence correlations and spin-orbit coupling effects are also considered. The AWCV5Z-PP pseudopotential basis set of Te atom is used. Spectroscopic parameters of the Λ-S and Ω states are obtained by solving radial Schrodinger equation. These results are reported at the first time. Permanent dipole moments of the Ω states and transition dipole moments of the a21↔X0+ and A1↔X0+ transitions are also calculated. Highly diagonally distributed Franck-Condon factors of the a21↔X0+ and A1↔X0+ transitions are obtained, the value of f00 is 0.9970 and 0.9980, respectively. Spontaneous radiative lifetimes of the a21 and A1 excited states are predicted. i.e. τ(a21) = 200.3 ns and τ(A1) = 84.3 ns. Only the main pump laser is required to driving a21↔X0+ and A1↔X0+ transitions. The laser wavelengths both are in the visible region. Doppler temperatures and recoil temperatures of laser cooling TeH- anion are also predicted.

19.
Soft Matter ; 15(33): 6615-6625, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31406972

RESUMO

Self-healing materials (SHMs) have been a research hot topic in recent years owing to their greatly improved longevity and safety in practical applications. Recently, research on SHMs has gradually expanded from structural materials to functional materials. Functional materials with self-healing properties (FMSH) require simultaneous repairing not only of the mechanical properties but of the functionalities from damaged cracks or wounds. It is more challenging to introduce both self-healing properties and a particular functionality to materials owing to the difficulties of preparing the materials and their more complex healing mechanism. Herein, we summarize the recent progress that has been made in FMSH, put forward insights from the perspectives of material preparation and healing mechanisms and highlight future developments for FMSH.

20.
Psychopharmacology (Berl) ; 236(11): 3281-3289, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31197434

RESUMO

RATIONALE: Juvenile social isolation (SI) and neglect is associated with a wide range of psychiatric disorders. While dysfunction of the corticolimbic pathway is considered to link various abnormal behaviors in SI models of schizophrenia, the enduring effects of early social deprivation on physiological properties of medium spiny neurons (MSNs) in nucleus accumbens (NAc) are not well understood. OBJECTIVES: This study investigated the impacts of juvenile SI on locomotor activity to methamphetamine (METH) and neurophysiological characteristics of MSNs in the core of NAc. METHODS: Socially isolated C57BL/6 mice experienced single housing for 4 weeks on postnatal day (PND) 21. The locomotor response to METH (1.0 mg/kg) was observed in both socially isolated and group-housed mice at PND 56. The effects of juvenile SI on the excitatory synaptic events in MSNs and the intrinsic excitability of MSNs in NAc core were investigated in other batches during PND 63-70. RESULTS: Socially isolated mice showed locomotor hypersensitivity to METH, although the expression of locomotor sensitization to METH in socially isolated mice was not different from group-housed mice. The recordings from MSNs of SI-reared mice exhibited higher frequency and smaller amplitude of miniature/spontaneous excitatory postsynaptic current than those from group-reared mice. Moreover, SI resulted in increased intrinsic excitability of MSNs in adult mice. CONCLUSIONS: These results demonstrate neuronal hyperactivity in the NAc of socially isolated mice, which could contribute to locomotor hypersensitivity to METH. Furthermore, the findings indicate a biological link between early negative life events and the vulnerability to psychostimulant-induced psychosis in adulthood.


Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Neurônios/efeitos dos fármacos , Núcleo Accumbens/citologia , Núcleo Accumbens/efeitos dos fármacos , Isolamento Social/psicologia , Animais , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Feminino , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Metanfetamina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Neuritos/efeitos dos fármacos , Neuritos/fisiologia , Neurônios/fisiologia , Núcleo Accumbens/fisiologia , Gravidez
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