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1.
Cell Calcium ; 96: 102406, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33848733

RESUMO

The effect of brain extracellular matrix (ECM) on synaptic plasticity remains controversial. Here, we show that targeted enzymatic attenuation with chondroitinase ABC (ChABC) of ECM triggers the appearance of new glutamatergic synapses on hippocampal pyramidal neurons, thereby increasing the amplitude of field EPSPs while decreasing both the mean miniature EPSC amplitude and AMPA/NMDA ratio. Although the increased proportion of 'unpotentiated' synapses caused by ECM attenuation should promote long-term potentiation (LTP), surprisingly, LTP was suppressed. The upregulation of small conductance Ca2+-activated K+ (SK) channels decreased the excitability of pyramidal neurons, thereby suppressing LTP. A blockade of SK channels restored cell excitability and enhanced LTP; this enhancement was abolished by a blockade of Rho-associated protein kinase (ROCK), which is involved in the maturation of dendritic spines. Thus, targeting ECM elicits the appearance of new synapses, which can have potential applications in regenerative medicine. However, this process is compensated for by a reduction in postsynaptic neuron excitability, preventing network overexcitation at the expense of synaptic plasticity.

2.
Neuroreport ; 32(7): 596-602, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33850085

RESUMO

Changes in the hippocampus are closely associated with learning and memory in Alzheimer's disease; however, it is not clear which morphological and cellular and subcellular changes are essential for learning and memory. Here, we accurately quantitatively studied the hippocampal microstructure changes in Alzheimer's disease model mice and analyzed the relationship between the hippocampal microstructure changes and learning and memory. Ten-month-old male APP/PS1 transgenic mice and age-matched nontransgenic littermate mice were randomly selected. The spatial learning and memory abilities were assessed using the Morris water maze. The volumes of each layer and numbers of neurons, dendritic spines and oligodendrocytes in the hippocampal subregions were investigated using unbiased stereological techniques. The APP/PS1 transgenic mice showed a decline in hippocampus-dependent spatial learning and memory abilities, smaller volumes of each layer (other than stratum radiatum) and fewer numbers of neurons, dendritic spine synapses and mature oligodendrocytes in the hippocampal subregions than nontransgenic mice. In particular, the decline of spatial learning ability was significantly correlated with the atrophy of lacunosum moleculare layer (LMol) and the decrease of hippocampal neurons and mature oligodendrocytes rather than dendritic spines. The CA1-3 fields (including LMol) atrophy was significantly correlated with the decrease both of neurons, dendritic spines and mature oligodendrocytes. However, the dentate gyrus atrophy was significantly correlated with the decrease of neurons and mature oligodendrocytes rather than dendritic spines. The loss of neurons, dendritic spines synapses and mature oligodendrocytes together caused the LMol atrophy and then led to a decline in hippocampus-dependent spatial learning ability in mice with Alzheimer's disease.

3.
Org Biomol Chem ; 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33890609

RESUMO

An I2-DMSO mediated oxidative amidation of methyl ketones using anthranils as masked N-nucleophiles has been developed for the direct synthesis of α-ketoamides with high atom-economy. This metal-free process involves reductive N-O bond cleavage of anthranils and oxidative C-N bond formation of methyl ketones under mild conditions. The iodo group and electrophilic formyl group provide multiple possibilities for further functionalization of α-ketoamides.

4.
5.
Transl Psychiatry ; 11(1): 222, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33859158

RESUMO

Running exercise was shown to have a positive effect on depressive-like symptoms in many studies, but the underlying mechanism of running exercise in the treatment of depression has not been determined. Parvalbumin-positive interneurons (PV+ interneurons), a main subtype of GABA neurons, were shown to be decreased in the brain during the depression. PGC-1α, a molecule that is strongly related to running exercise, was shown to regulate PV+ interneurons. In the present study, we found that running exercise increased the expression of PGC-1α in the hippocampus of depressed mice. Adult male mice with PGC-1α gene silencing in the hippocampus ran on a treadmill for 4 weeks. Then, depression-like behavior was evaluated by the behavioral tests, and the PV+ interneurons in the hippocampus were investigated. We found that running exercise could not improve depressive-like symptoms or increase the gene expression of PV because of the lack of PGC-1α in the hippocampus. Moreover, a lack of PGC-1α in the hippocampus decreased the number and activity of PV+ interneurons in the CA3 subfield of the hippocampus, and running exercise could not reverse the pathological changes because of the lack of PGC-1α. The present study demonstrated that running exercise regulates PV+ interneurons through PGC-1α in the hippocampus of mice to reverse depressive-like behaviors. These data indicated that hippocampal PGC-1α-mediated positive effects on parvalbumin interneurons are required for the antidepressant actions of running exercise. Our results will help elucidate the antidepressant mechanism of running exercise and identify new targets for antidepressant treatment.

8.
Signal Transduct Target Ther ; 6(1): 162, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33907179

RESUMO

Purines and their derivatives, most notably adenosine and ATP, are the key molecules controlling intracellular energy homoeostasis and nucleotide synthesis. Besides, these purines support, as chemical messengers, purinergic transmission throughout tissues and species. Purines act as endogenous ligands that bind to and activate plasmalemmal purinoceptors, which mediate extracellular communication referred to as "purinergic signalling". Purinergic signalling is cross-linked with other transmitter networks to coordinate numerous aspects of cell behaviour such as proliferation, differentiation, migration, apoptosis and other physiological processes critical for the proper function of organisms. Pathological deregulation of purinergic signalling contributes to various diseases including neurodegeneration, rheumatic immune diseases, inflammation, and cancer. Particularly, gout is one of the most prevalent purine-related disease caused by purine metabolism disorder and consequent hyperuricemia. Compelling evidence indicates that purinoceptors are potential therapeutic targets, with specific purinergic agonists and antagonists demonstrating prominent therapeutic potential. Furthermore, dietary and herbal interventions help to restore and balance purine metabolism, thus addressing the importance of a healthy lifestyle in the prevention and relief of human disorders. Profound understanding of molecular mechanisms of purinergic signalling provides new and exciting insights into the treatment of human diseases.

9.
Ren Fail ; 43(1): 500-509, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33706645

RESUMO

BACKGROUND: Macroscopic hematuria after wasp sting has been reported in Asia to occur before acute kidney injury (AKI), and is often used by clinicians as a sign indicating the need for intensive care and blood purification therapy. However, there is no study on the clinical characteristics and prognosis of this symptom. METHODS: The clinical data of 363 patients with wasp sting admitted to Suining Central Hospital from January 2016 to December 2018 were retrospectively analyzed. At admission, the poisoning severity score (PSS) was used as the criterion for severity classification. According to the presence of macroscopic hematuria, the patients were divided into macroscopic hematuria and non-macroscopic hematuria group. RESULTS: Of the 363 wasp sting patients, 219 were male and 144 were female, with a mean age of 55.9 ± 16.3 years. Fifty-one (14%) had macroscopic hematuria, 39 (10.7%) had AKI, 105 (28.9%) had rhabdomyolysis, 61 (16.8%) had hemolysis, 45 (12.4%) went on to received hemodialysis, and 14 (3.9%) died. The incidence of AKI in macroscopic hematuria group was 70.6%, and oliguric renal failure accounted for 72.2%. Patients with macroscopic hematuria had significantly higher PSS (2.2 ± 0.5 vs. 1.1 ± 0.3, p < .001). CONCLUSION: Macroscopic hematuria can be regarded as a surrogate marker of deteriorating clinical outcome following wasp stings. In wasp sting patients with symptoms of macroscopic hematuria or serum LDH higher than 463.5 u/L upon admission, the risk of AKI increases significantly, therefore hemodialysis should be considered. The PSS is helpful in early assessment of the severity of wasp sting patients.

10.
Asia Pac J Public Health ; : 10105395211001652, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33729008

RESUMO

The COVID-19 (coronavirus disease 2019) pandemic is an emerging, rapidly evolving situation. This study aims to investigate Chinese people's perceptions of COVID-19 and its effects on varied responses to take public health precautions and self-reported protective measures. The survey data were collected from 565 Chinese respondents online from January 25, 2020, to February 4, 2020. Respondents reported a highly perceived risk, knowledge, and self-efficacy associated with the spread of pandemic, and a strong agreement on public health precaution. The more possibilities pneumonia caused by COVID-19 was perceived as severe disease, the more chances public health precautions were taken, but intentions to take self-reported protective measures decreased. Neither infection risk of family member nor full awareness of increasing number of cases had any significant effect on respondents' decision to take personal health responses, suggesting urgent needs to offer health advice to those who deliberately ignore infection risk.

11.
Cancer Biol Med ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33724741

RESUMO

OBJECTIVE: In this post-hoc analysis, we evaluated anlotinib treatment-induced hypertension as a potential predictive factor of efficacy in esophageal squamous cell carcinoma (ESCC) patients. METHODS: A total of 109 patients enrolled in the anlotinib group in a phase 2 trial were included. The tumor response was assessed by computed tomography at week 3, week 6, and then every 6 weeks until progressive disease was observed. The primary endpoint of the study was progression free survival (PFS). The secondary endpoints included overall survival (OS) and objective response rate (ORR). RESULTS: In all patients, the median PFS was 3.02 months [95% confidence interval (CI): 2.63-3.65 months] and the OS was 6.11 months (95% CI: 4.40-7.79 months). The ORR was 7.34% (95% CI: 3.22%-13.95%). A total of 59 (54%) patients were diagnosed with treatment-induced hypertension (Group A), and the remaining patients (n = 50, 46%) were in Group B. Baseline prognostic factors were similar between the 2 groups. Patients in Group A had a longer PFS and OS and higher ORR. When stratifying patients using a previously known history of hypertension, treatment-induced hypertension was a predictor only for patients without previous hypertension, who had longer PFS [hazard ratio (HR): 0.40, 95% CI: 0.24-0.68] and OS (HR: 0.37, 95% CI: 0.21-0.67). CONCLUSIONS: We showed, for the first time, a correlation between treatment-induced hypertension and better prognoses in recurrent or metastatic ESCC patients treated with anlotinib, without a previously known history of hypertension. Treatment-induced hypertension may be a simple and low cost predictor for anlotinib antitumor efficacy in these patients, which may also reflect the intended target inhibition.

12.
Anal Chim Acta ; 1152: 338242, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648651

RESUMO

In this work, ultrasmall Au nanoparticles decorated bimetallic metal-organic framework (US Au NPs@AuZn-MOF) hybrids were facilely prepared by a sequential ion exchange and in-situ chemical reduction strategy. Numerous of Au nanoparticles with size less than 5 nm was homogeneously dispersed on the surface of the whole bimetallic AuZn-MOF polyhedrons. The integration of ultrasmall Au nanoparticles greatly enhanced the electron transfer capacity and electrochemical active surface area of the metal-organic framework host. Compared with the pristine Zn-MOF, bimetallic AuZn-MOF, the as-synthesized US Au NPs@AuZn-MOF hybrids exhibited remarkably promoted electrochemical activity toward the oxidation and sensing of endocrine-disrupting chemical (EDC) estrone. As a result, a highly sensitive electrochemical sensing platform was developed for the detection of estrone in the range of 0.05 µM-5 µM with limit of detection of 12.3 nM (S/N = 3) and sensitivity of 101.3 µA-1 µM-1 cm-2. Considering the structural diversity of MOFs and superior property of ultrasmall Au nanoparticles, the strategy proposed here may open a new avenue for the design and synthesis of other high-activity nanomaterials for electrochemical sensing or other challenging fields.

13.
Basic Res Cardiol ; 116(1): 22, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33755785

RESUMO

Adenosine is an ubiquitous extracellular signaling molecule and plays a fundamental role in the regulation of coronary microcirculation through activation of adenosine receptors (ARs). Adenosine is regulated by various enzymes and nucleoside transporters for its balance between intra- and extracellular compartments. Adenosine-mediated coronary microvascular tone and reactive hyperemia are through receptors mainly involving A2AR activation on both endothelial and smooth muscle cells, but also involving interaction among other ARs. Activation of ARs further stimulates downstream targets of H2O2, KATP, KV and KCa2+ channels leading to coronary vasodilation. An altered adenosine-ARs signaling in coronary microcirculation has been observed in several cardiovascular diseases including hypertension, diabetes, atherosclerosis and ischemic heart disease. Adenosine as a metabolite and its receptors have been studied for its both therapeutic and diagnostic abilities. The present review summarizes important aspects of adenosine metabolism and AR-mediated actions in the coronary microcirculation.

14.
Acta Biomater ; 126: 183-198, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33711525

RESUMO

Selective cell retention (SCR) has been widely used as a bone tissue engineering technique for the real-time fabrication of bone grafts. The greater the number of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) retained in the scaffold, the better the osteoinductive and angiogenic properties of the scaffold's microenvironment. Improved bioscaffold properties in turn lead to improved bone graft survival, bone regeneration, and angiogenesis. Laminin plays a key role in cell-matrix adhesion, cell proliferation, and differentiation. We designed a collagen-binding domain (CBD) containing the core functional amino acid sequences of laminin α4 (CBD-LN peptide) to supplement the functional surface of a collagen-based decalcified bone matrix (DBM) scaffold. This scaffold promoted MSCs and EPCs early cell adhesion through up-regulating the expression of integrin α5ß1 and integrin αvß3 respectively, thus accelerated the following cell spreading, proliferation, and differentiation. Interestingly, it promoted the retention of MSCs (CD90+/CD105+ cells) and EPCs (CD31+ cells) in the scaffold following the use of clinical SCR technology. Furthermore, the DBM/CBD-LN scaffold induced the formation of type H vessels through the activation of the HIF-1α signaling pathway. The DBM/CBD-LN scaffold displayed rapid bone formation and angiogenesis in vivo, suggesting that it might be used as a new biomaterial in bone tissue engineering. STATEMENT OF SIGNIFICANCE: Selective cell retention technology (SCR) has been utilized in clinical settings to manufacture bioactive bone grafts. Specifically, demineralized bone matrix (DBM) is a widely-used SCR clinical biomaterial but it displays poor adhesion performance and angiogenic activity. In this work, we designed a collagen-binding domain (CBD) containing the core functional amino acid sequences of laminin α4 to supplement the functional surface of a collagen-based DBM scaffold. This bioscaffold promoted SCR-mediated MSCs and EPCs early cell adhesion, thus accelerated the following cell spreading, proliferation, and differentiation. Our results indicate this bioscaffold greatly induced osteogenesis and angiogenesis in vivo. In general, this bioscaffold has a good prospect for SCR application and may provide highly bioactive bone implant in clinical environment.

15.
Neurochem Res ; 46(6): 1514-1539, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33719004

RESUMO

Gut microbial dysbiosis and alteration of gut microbiota composition in Parkinson's disease (PD) have been increasingly reported, no recognized therapies are available to halt or slow progression of PD and more evidence is still needed to illustrate its causative impact on gut microbiota and PD and mechanisms for targeted mitigation. Epidemiological evidence supported an association between milk intake and a higher incidence of Parkinson's disease (PD), questions have been raised about prospective associations between dietary factors and the incidence of PD. Here, we investigated the significance of casein in the development of PD. The mice were given casein (6.75 g/kg i.g.) for 21 days after MPTP (25 mg/kg i.p. × 5 days) treatment, the motor function, dopaminergic neurons, inflammation, gut microbiota and fecal metabolites were observed. The experimental results revealed that the mice with casein gavage after MPTP treatment showed a persisted dyskinesia, the content of dopamine in striatum and the expression of TH in midbrain and ileum were decreased, the expression of Iba-1, CD4, IL-22 in midbrain and ileum increased continuously with persisted intestinal histopathology and intestinal barrier injury. Decreased intestinal bile secretion in addition with abnormal digestion and metabolism of carbohydrate, lipids and proteins were found, whereas these pathological status for the MPTP mice without casein intake had recovered after 24 days, no significant differences were observed with regard to only treated with casein. Our study demonstrates that intestinal pathologic injury, intestinal dysbacteriosis and metabolism changes promoted by casein in MPTP mice ultimately exacerbated the lesions to dopaminergic neurons.

16.
Cancer Med ; 10(5): 1681-1689, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33586360

RESUMO

BACKGROUND: Currently, there are no randomized trials on the effect of antiangiogenic therapy in patients with esophageal squamous cell carcinoma (ESCC). The following study investigated the efficacy and safety of anlotinib in patients with advanced ESCC who were previously treated with chemotherapy. METHODS: This randomized, placebo-controlled, double-blind phase 2 trial (NCT02649361) was conducted in 13 Chinese hospitals. Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC who were previously treated with chemotherapy, and were randomly assigned (2:1) to receive oral anlotinib 12 mg or placebo on days 1-14 (repeated every 21 days). The primary endpoint was progression-free survival (PFS). RESULTS: One hundred and sixty-five patients were randomly assigned to the anlotinib (n = 110) or the placebo (n = 55) arm. Median PFS was 3.02 months (95% CI 2.63-3.65) in the anlotinib group and 1.41 months (95% CI 1.38-1.41) in the placebo group (hazard ratio 0.46 [95% CI 0.32-0.66]; p < 0.001). The most common treatment-related adverse events of grade 3 or 4 were hypertension (17 [16%] patients), decreased appetite (6 [6%] patients), and hyponatremia (4 [4%] patients) in the anlotinib group and decreased appetite (2 [4%] patients) in the placebo group. Three (3%) deaths in the anlotinib group were considered as drug related, while there were no treatment-related deaths in the placebo group. CONCLUSIONS: The use of anlotinib in previously treated, recurrent, or metastatic ESCC patients significantly improved PFS compared with placebo. Our findings suggest that antiangiogenesis might be an important therapeutic target in advanced ESCC. CLINICAL TRIALS REGISTRATION: Study of Anlotinib in Patients With Esophageal Squamous Cell Carcinoma (ALTER1102), NCT02649361.

17.
Purinergic Signal ; 17(1): 137-138, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33537870
18.
Crit Rev Eukaryot Gene Expr ; 31(1): 71-78, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33639057

RESUMO

The present study was conducted to investigate the molecular mechanism of propofol in inhibiting the proliferation of mouse cardiac fibroblasts (CFs) induced by angiotensin II (Ag II). The ventricles of SPF mice from Kunming were cultured for the second to third generation of CFs under aseptic condition. On the basis of the different adding conditions, the mice were divided into five groups: (1) control group: no drug were added; (2) Ag II group: 100 nmol/L Ag II were added; (3) 10 µmol/L propofol + 100 nmol/L Ag II group; (4) 30 µmol/L propofol + 100 nmol/L Ag II group; (5) 50 µmol/L propofol + 100 nmol/L Ag II group. The effects of propofol on the proliferation of CFs induced by Ag II, the expression of CFs ET-1, the activity of NADPH oxidase and the formation of ROS were analyzed. In addition, our study also explored the potential role of Akt-eNOS-nitric oxide pathway regarding the inhibition of proliferation of Ag II induced CFs by propofol. We found that the proliferation of CFs, the secretion of ET-1, the activity of NADPH oxidase and the level of intracellular ROS and fibronectin expression were significantly increased after CFs exposure to Ag II for 24 h. The abovementioned indexes decreased significantly in CFs after treated with propofol for 24 h (10, 30, or 50 µmol/L) with significant statistical difference (P < 0.05). Akt and eNOS siRNA transfection significantly decreased the levels of Akt and eNOS protein, respectively. Blocking pathway of Akt-eNOS-nitric oxide decreased the inhibitory effect of propofol on Ag II-induced cell proliferation of CFs. Propofol exerts effect in inhibiting ET-1 and fibronectin expression and the formation of ROS induced by Ag II. Moreover, Akt-eNOS-nitric oxide signaling pathway may be involved in the effect of propofol on the proliferation of CFs induced by Ag II.

19.
BMC Complement Med Ther ; 21(1): 63, 2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33583417

RESUMO

BACKGROUND: The prevalence of CAM use is increasing. This integrative review investigated New Zealand healthcare professionals' practice of, attitudes toward, and knowledge about complementary and alternative medicine (CAM). METHODS: Literature search was conducted in four databases from inception to April 2020. Studies were included if they reported results from primary data collection on practice of, attitudes toward, or knowledge about CAM amongst New Zealand healthcare professionals. RESULTS: Eleven studies (two of 'high-quality', seven of 'moderate-quality', and two of 'low-quality') were identified with 2060 healthcare professionals including general practitioners (GPs), nurses, midwives, pharmacists, physiotherapists, and medical specialists. New Zealand healthcare professionals were generally positive regarding CAM use, but have concerns on the scientific evidence, regulation, safety, financial costs of CAM, and encourage an evidence-based CAM practice and stronger CAM regulation. Findings indicated that around 25% of GPs practise CAM, and 82.3% refer patients to CAM practitioners. When treating pregnant women, 48.4% of physiotherapists practise acupuncture, and 37.3% of midwives recommend CAM. GPs believe that acupuncture is the most helpful CAM modality, and most commonly practiced and referred patients to acupuncture. Up to 58% of GPs and Plunket nurses wanted to receive further education on CAM, and up to 66.7% GPs favour the idea CAM should be included in medical curriculums. CONCLUSIONS: Nine of the 11 included studies were of moderate to high quality, thus enhancing the reliability of the review findings. In order to better manage CAM in New Zealand New Zealand clinical settings, there is a need to invest in CAM research and education, and enhance CAM regulation. This review is a first step in developing an evidence base to offer insights for further development of effective CAM policies regarding safety, efficacy, regulation and integration in New Zealand.

20.
Medicine (Baltimore) ; 100(5): e23946, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592847

RESUMO

BACKGROUND: Chronic fatigue syndrome (CFS) is a relatively complex and disabling illness with a substantial economic burden and functional impairment. Until now, many CFS patients lack appropriate healthcare. Acupoint catgut embedding is an effective and emerging alternative therapy for CFE. With this research, we endeavor to investigate the effect and safety of ACE for CFS. METHODS: Eight databases will be searched from inception to December 2020: PubMed, EMBASE, The Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chong-Qing VIP database, and Wan-fang database. We regard studies as eligible for inclusion if they were RCTs done in CFS patients, compare acupoint catgut embedding to another treatment strategy, and report fatigue changes at the end of the intervention period. Two independent reviewers complete the study selection, data extraction, and the risk of bias assessment. We assess pooled data using a random-effects model through Revman software (v.5.3) and Stata (version 15.0). ETHICS AND DISSEMINATION: Ethics approval is not required because the individual patient data will not be involved, with no privacy concerns. This systematic review and meta-analysis will provide a reference for CFS patients and clinicians on the non-drug interventions. We will publish and disseminate the results of this review in a peer-reviewed journal or relevant conference. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/7SHD9 (https://osf.io/7shd9).


Assuntos
Pontos de Acupuntura , Categute , Síndrome de Fadiga Crônica/terapia , Inclusão do Tecido/métodos , Humanos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do Tratamento
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