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1.
Zhen Ci Yan Jiu ; 45(3): 233-6, 2020 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-32202716

RESUMO

OBJECTIVE: To observe the influence of Xiao's "xingnaofusu" needling (the technique for resuscitation) on regaining consciousness in the patients with persistent vegetative state (PVS). METHODS: A total of 50 patients of PVS were randomized into an observation group and a control group, 25 cases in each. The patients in the control group were treated by the routine western medicine, and those in the observation group treated by Xiao's "xingnaofusu" needling and routine western medicine. Baihui (GV20), Dingshen (Extra) to Shangen (Extra) (penetrating technique), Fengchi (GB20) to GB20 (penetrating technique), Neiguan (PC6) to Waiguan (TE5) (penetrating technique), Hegu (LI4) to Laogong (HT8) (penetrating technique) and Taichong (LR3) to Yongquan (KI1) (penetrating technique) were selected. The treatment was given once a day, 10 days as one treatment course, 3 courses in total. The coma recovery scale-revised (CRS-R) score, the modified Ashworth scale (MAS) score and the Glasgow coma scale (GCS) were separately compared before and after the treatment. Additionally, CT scanning was adopted to measure the width of the third ventricle before and after treatment so as to evaluate the clinical therapeutic effect. RESULTS: After the treatment, the CRS-R and GCS scores in the two groups increased remarkably, and MAS score reduced obviously as compared with that before the treatment(P<0.05); and the CRS-R and GCS scores were higher, and MAS score lower in the observation group than those in the control group(P<0.05). Compared with the control group, the width of the third ventricle reduced obviously in the observation group after the treatment(P<0.05). At the end of the treatment courses, the effective rate was 79.2%(19/24)in the observation group and was 47.8%(11/23) in the control group. The effective rate of the observation group was obviously higher than that of the control group (P<0.05). CONCLUSION: Xiao's "xingnaofusu" needling can remarkably improve the central nerve function, promote the recovery of brain function and the motor function of limbs, reduce the width of the third ventricle and improve the clinical therapeutic effect of regaining consciousness in the patients with PVS.

3.
Zhen Ci Yan Jiu ; 44(10): 772-6, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31657170

RESUMO

The clinical and experimental researches of acupuncture and moxibustion on endometriosis during past 15 years were collected. The research progress underling the mechanism of acupuncture and moxibustion on endometriosis was summarized. By taken Chinese characters, i.e. "acupuncture-moxibustion" and "endometriosis" as well as the English words, i.e. "acupuncture therapy" and "endometriosis" as the searching words, the relevant articles were retrieved from Pubmed, Embase, Chinese China National Knowledge Infrastructure, Wanfang Database, Chongqing VIP and the China Biology Medicine Disc etc. The retrieval time was from January 2003 to October 2018. As a result, 41 articles of clinical studies and 18 articles of animal experiments were screened. Of them, 20 articles (including 18 articles of animal experiments and 2 articles of clinical trial) are related to the mechanism underling acupuncture and moxibustion on endometriosis. In term of the impacts on growth factors, enzymes and enzyme inhibitors, the mechanism of acupuncture and moxibustion was explored on the analgesia for endometriosis, the inhibition of ectopic tissue angiogenesis and invasive adhesion, as well as the regulation of immune function and endocrine. Moreover, the limitation and prospect on the current researches were proposed so as to provide the more reliable evidence for clinical treatment of endometriosis with acupuncture and moxibustion.


Assuntos
Terapia por Acupuntura , Endometriose , Moxibustão , Animais , China , Endometriose/terapia , Feminino , Humanos
4.
J Biomol Struct Dyn ; : 1-7, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31588852

RESUMO

A water-soluble variant of the transmembrane domain of the human mu opioid receptor (wsMOR-TM) was previously characterized. This study explored whether the full-length version of the engineered water-soluble receptor, (wsMOR-FL), could be overexpressed in Escherichia coli and if it would retain water solubility, binding capability and thermostability. wsMOR was over-expressed and purified in E. coli BL21(DE3) cells (EMD/Novagen) as we reported previously for the wsMOR-TM. Both native N and C termini were added back to the highly engineered wsMOR-TM. Six His-tag was added in the N terminus for purification purposes. The wsMOR-FL was characterized using atomic force microscope for its monomeric state, circular dichroism for its secondary structure and thermostability. Its binding with naltrexone is also determined. Compared to the native human MOR, wsMOR-FL displays similar helical secondary structure content and comparable affinity (nM) for the antagonist naltrexone. The secondary structure of the receptor remains stable within a wide range of pH (6-9). In contrast to the transmembrane portion, the secondary structure of full-length receptor tolerated a wide range of temperature (10-90 °C). The receptor remains predominantly as a monomer in solution, as directly imaged using atomic force microscopy. This study demonstrated that functional full-length water-soluble variant of human mu receptor can be over-expressed and purified using an E. coli over-expression system. This provides a novel tool for the investigation of structural and functional properties of the human MOR. N- and C-termini strengthened the thermostability of the protein in this specific water soluble variant. Communicated by Ramaswamy H. Sarma.

5.
Stem Cell Res Ther ; 10(1): 244, 2019 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391117

RESUMO

BACKGROUND: Tissue regeneration disorder after endometrial injury is an important cause of intrauterine adhesions, amenorrhea, and infertility in women. Both bone marrow mesenchymal stem cell (BMSC) transplantation and electroacupuncture (EA) are promising therapeutic applications for endometrial injury. This study examined their combined effects on thin endometrium in rats and the possible mechanisms underlying these effects. METHODS: A thin endometrial model was established in Sprague-Dawley (SD) rats by perfusing 95% ethanol into the right side of the uterus. The wounds were randomly treated with PBS (model group), BMSCs only (BMSC group), EA only (EA group), and BMSCs combined with EA (BMSC + EA group). Endometrial morphological alterations were observed by hematoxylin and eosin (H&E) staining. Changes in markers of epithelial and stromal endometrium cells, endometrial receptivity-related chemokines, and paracrine factors were detected using immunohistochemistry, western blotting, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Finally, the functional recovery of the uterus was evaluated by determining the rate of embryo implantation. RESULTS: As shown by endometrial morphology, the damaged uteri in all the treatment groups recovered to some extent, with the best effects observed in the BMSC + EA group. Further studies showed that EA promoted the migration of transplanted BMSCs to damaged uteri by activating the stromal cell-derived factor-1/C-X-C chemokine receptor type 4 (SDF-1/CXCR4) axis. As compared with the other groups, upregulated expression of endometrial cytokeratin and vimentin, increased secretion of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in endometrial lesions, and improved embryo implantation rates on the 8th day of pregnancy were found in the BMSC + EA group. CONCLUSIONS: EA plays an important role in supporting BMSCs in the repair of thin endometrium, most likely by promoting the migration of BMSCs and enhancing the paracrine effect of BMSCs.

6.
Int J Hypertens ; 2019: 8268573, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31316827

RESUMO

Objective: To estimate the additive interaction of body mass index (BMI) and family history of hypertension (FHH) on hypertension and explore whether the interaction could be influenced by behavioural risk factors. Methods: The cross-sectional data on 5791 participants were from the China National Health Survey in Gansu province in 2016. We assessed the additive interaction by calculating the relative excess risk due to interaction (RERI), the attributable proportion due to interaction (AP), and the synergy index (SI). Results: ORs for hypertension were highest in Han (13.52, 95% CI: 9.45 to 19.34) and Yugur (13.85, 95% CI: 8.48 to 22.63) with the combination of obesity and FHH. The interaction of BMI and FHH was significant in Han people, with the RERI, AP, and SI and their 95% CIs being 2.48 (1.13 to 3.82), 0.33 (0.19 to 0.47), and 1.61 (1.26 to 2.07) for overweight and FHH and 6.32 (1.91 to 10.73), 0.47 (0.27 to 0.67), and 2.02 (1.33 to 3.07) for obesity and FHH, respectively. The interaction of BMI and FHH was not significant in Yugur people. Adjustment for behavioural risk factors had little influence on the interactions, and risks of hypertension remained increased. Conclusions: BMI and FHH were associated with hypertension, and the interaction of BMI and FHH on hypertension was significant in Han but not in Yugur people. Behavioural risk factors had little influence on the associations and interactions. The exacerbation of hypertension risks by overweight or obesity in hypertension families deserves attention in weight control and community care.

7.
Anesth Analg ; 128(6): 1328-1335, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31094808

RESUMO

BACKGROUND: Opioid dependence is a major public health issue without optimal therapeutics. This study investigates the potential therapeutic effect of dezocine, a nonaddictive opioid, in opioid dependence in rat models. METHODS: Dezocine was administered intraperitoneally to a morphine-dependent rat model to investigate its effect on withdrawal and conditioned place preference (CPP). Effect of dezocine on morphine withdrawal syndrome and CPP was analyzed using 2-way analysis of variance (ANOVA) followed by Tukey's post hoc test. Buprenorphine and vehicle solution containing 20% (v/v) dimethyl sulfoxide were used for positive and negative control, respectively. The astrocytes activation in nucleus accumbens was assessed by immunofluorescence assay of glial fibrillary acidic protein. Effect of dezocine and buprenorphine on the internalization of κ opioid receptor (KOR) was investigated using Neuro2A expressing KOR fused to red fluorescent protein tdTomato (KOR-tdT). Buprenorphine and dezocine were screened against 44 G-protein-coupled receptors, ion channels, and transporter proteins using radioligand-binding assay to compare the molecular targets. RESULTS: The mean withdrawal score was reduced in rats treated with 1.25 mg·kg dezocine compared to vehicle-treated control animals starting from the day 1 (mean difference: 7.8; 95% confidence interval [CI], 6.35-9.25; P < .0001 by 2-way ANOVA). Significance was observed at all treatment days, including day 7 (mean difference: 2.13; 95% CI, 0.68-3.58; P < .001 by 2-way ANOVA). Furthermore, dezocine inhibited the reinstatement of morphine-induced CPP (mean difference: 314; 95% CI, 197.9-430.1; P < .0001 by 2-way ANOVA) compared to the control group. Chronic morphine administration induced astrocytes activation in nucleus accumbens, which was attenuated by dezocine. Dezocine blocked the agonist-induced KOR internalization in vitro, 1 of the mechanisms involved in the downstream signaling and development of opioid dependence. Dezocine had affinity to norepinephrine and serotonin transporters and sigma-1 receptor, whereas buprenorphine showed no activity against these targets. CONCLUSIONS: Dezocine could potentially be used to alleviate opioid dependence. Due to the unique molecular target profile different from buprenorphine, it might have important value in studying the mechanisms of morphine dependence and developing novel therapeutic approaches.


Assuntos
Analgésicos Opioides/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Dependência de Morfina/tratamento farmacológico , Morfina/efeitos adversos , Antagonistas de Entorpecentes/farmacologia , Tetra-Hidronaftalenos/farmacologia , Análise de Variância , Animais , Astrócitos/efeitos dos fármacos , Buprenorfina/administração & dosagem , Linhagem Celular , Relação Dose-Resposta a Droga , Imunofluorescência , Proteína Glial Fibrilar Ácida/metabolismo , Masculino , Núcleo Accumbens/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores Opioides kappa/metabolismo
8.
Analyst ; 144(8): 2523-2530, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30830136

RESUMO

Ratiometric fluorescent nanosensors were developed to detect mercury ions (Hg2+) using enhanced dual emissions from glutathione stabilized gold nanoclusters/indium-based metal-organic frameworks modified with cysteine (AuNCs/MIL-68(In)-NH2/Cys). The nanosensors exhibited bright pink fluorescence with AuNCs evenly distributed on MIL-68(In)-NH2. Under 370 nm excitation, the obtained sensor presented double fluorescence emission around 438 nm and 668 nm, which was attributed to MIL-68(In)-NH2 and GSH-AuNCs, respectively. The fluorescence emission was remarkably enhanced after modification with Cys. In the presence of Hg2+, the red fluorescence peak at 668 nm was quenched, while the blue fluorescence peak at 438 nm was slightly altered. The prepared AuNCs/MIL-68(In)-NH2/Cys nanosensors exhibited two linear ranges for the detection of Hg2+, namely from 20 pM to 0.2 µM and 0.2 µM to 60 µM, with a detection limit of 6.7 pM. They also presented high selectivity towards other ions and good performance in real water samples. Moreover, a radial star-shaped microfluidic paper-based analytical device (µPAD), as a straightforward and convenient platform, was successfully fabricated for the visual detection of Hg2+ with a wide detection range from 5 nM to 50 µM.

9.
Front Neurosci ; 13: 6, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30723394

RESUMO

Previous studies by our group have demonstrated that the transplantation of exogenous platelet-derived growth factor (PDGF)-AA-overexpressing oligodendrocyte progenitor cells (OPCs) promotes tissue repair and recovery of neurological function in a rat model of spinal cord injury (SCI). However, it remains unclear whether treatment with PDGF-AA also affects endogenous oligodendrocytes (OLs) or even neurons, thus promoting further functional recovery after SCI. In the present study, we evaluated the therapeutic potential of PDGF-AA treatment by direct subcutaneous injection of PDGF-AA immediately after SCI. We demonstrated that PDGF-AA injection resulted in increased tissue sparing, myelination and functional recovery in rats following SCI. Further experimentation confirmed that PDGF-AA increased the survival of endogenous OPCs and OLs, and promoted the proliferation of OPCs and their differentiation into OLs. Moreover, PDGF-AA also protected motor neurons from death in the injured spinal cord. These results indicated that PDGF-AA administration may be an effective treatment for SCI.

10.
Cancer Med ; 8(3): 1024-1033, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30714683

RESUMO

The impact of adjuvant radiotherapy in pT3N0 rectal cancer is controversial. We aimed to determine the risk factors for cancer-specific survival (CSS) among these patients and to develop a risk-stratification system to identify which of these patients would benefit from adjuvant radiotherapy. In this review of the Surveillance, Epidemiology, and End Results database (2010-2014), we analyzed the data of pT3N0 rectal cancer patients who had not undergone neoadjuvant radiotherapy. Prognostic factors were identified using the Cox proportional hazards model, and risk scores were derived according to the ß regression coefficient. A total of 1021 patients were identified from the database search. The overall 5-year CSS was 86.31%. Multivariate analysis showed that age (P < 0.001), tumor differentiation (P = 0.044), number of nodes resected (P = 0.032), marital status (P = 0.005), and radiotherapy (P = 0.006) were independent prognostic factors for CSS. A risk-stratification system composed of age, tumor differentiation, and number of nodes resected was generated. Low-risk patients had better CSS than high-risk patients (92.13% vs 72.55%, P < 0.001). The addition of radiotherapy to surgery doubled the CSS among the high-risk patients (42.06% vs 91.26%, P = 0.001) but produced no survival benefit among the low-risk patients (93.36% vs 96.38%, P = 0.182). Our risk-stratification model based on age, tumor differentiation, and number of nodes resected predicted the outcomes of pT3N0 rectal cancer patients. This model could help identify patients who may benefit from adjuvant radiotherapy.

11.
Artigo em Inglês | MEDLINE | ID: mdl-30327681

RESUMO

Objectives: To conclude the evidence from systematic reviews (SRs) and meta-analyses assessing the effectiveness of acupuncture to treat couples with subfertility undergoing ART. Methods: We searched the major databases from their inception to March 2018: PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chongqing VIP, and Sino-Med (the Chinese database). The primary outcomes of the overview were live birth and clinical pregnancy, and secondary outcomes were ongoing pregnancy, miscarriage, and adverse events. Study selection, quality assessment, and data extraction were performed independently by two review authors. Review methodological quality was assessed by using the AMSTAR tool, and the quality of the evidence was rated by GRADE methods. Results: Eleven systematic reviews were included and published between 2009 and 2017. Our study showed that the acupuncture treatment seems to be a useful tool to improve the clinical pregnancy rate in patients who undergo assisted reproduction therapy. However, there was no evidence that acupuncture had any effect on live birth rate, ongoing pregnancy rates, or miscarriage regardless of whether acupuncture was performed around the time of oocyte retrieval or around the day of embryo transfer; this evidence is inconclusive because of the low quality of the included studies. Conclusions: The evidence for acupuncture to treat couples with subfertility undergoing ART remains unclear. Further research is needed, with high-quality trials undertaken and reported.

13.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 34(3): 237-241, 2018 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-29773105

RESUMO

Objective To analyze the therapeutic effect of green tea polyphenols (GTP) in mice with colitis induced by TNBS and its possible mechanism. Methods Colitis was induced by TNBS in BALB/C mice. The mice were randomly divided into GTP group (n=10) and TNBS model group (n=10). Mice in the GTP group were given GTP [0.2 mL at a dose level of 100 mg/(kg.d)] by oral gavage, and mice in the model group were given normal saline [0.2 ml/d] by gavage. Four weeks later, the mice were sacrificed. Disease activity index (DAI) and inflammatory score were evaluated by HE staining. The levels of interleukin 10 (IL-10), IL-6 and tumor necrosis factor α (TNF-α) were detected by ELISA. The expressions and localization of ZO-1 and claudin-1 were identified with immunofluorescence technique. Western blot analysis was performed to detect the expressions of ZO-1, claudin-1, p-JAK2 and p-STAT3 proteins. Results GTP decreased the DAI and inflammatory score, and reduced the levels of TNF-α and IL-6 in TNBS-induced colitis mice at three and four weeks after the administration. Meanwhile, the levels of ZO-1 and claudin-1 increased in the mice of GTP group when compared with those in model group. Western blot analysis showed that GTP down-regulated the JAK2/STAT3 signaling pathway in the intestinal mucosa. Conclusion GTP has a significant therapeutic effect on TNBS-induced colitis through down-regulating the JAK2/STAT3 signaling pathway.


Assuntos
Camellia sinensis/química , Colite/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Janus Quinase 2/metabolismo , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Fator de Transcrição STAT3/metabolismo , Animais , Claudina-1/genética , Claudina-1/metabolismo , Colite/induzido quimicamente , Colite/genética , Colite/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Janus Quinase 2/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fator de Transcrição STAT3/genética , Transdução de Sinais/efeitos dos fármacos , Chá/química , Ácido Trinitrobenzenossulfônico/efeitos adversos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
14.
ACS Nano ; 12(5): 4218-4223, 2018 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-29634231

RESUMO

Opioid neuropeptides play a significant role in pain perception, appetite regulation, sleep, memory, and learning. Advances in understanding of opioid peptide physiology are held back by the lack of methodologies for real-time quantification of affinities and kinetics of the opioid neuropeptide-receptor interaction at levels typical of endogenous secretion (<50 pM) in biosolutions with physiological ionic strength. To address this challenge, we developed all-electronic opioid-neuropeptide biosensors based on graphene microelectrodes functionalized with a computationally redesigned water-soluble µ-opioid receptor. We used the functionalized microelectrode in a bias-free charge measurement configuration to measure the binding kinetics and equilibrium binding properties of the engineered receptor with [d-Ala2, N-MePhe4, Gly-ol]-enkephalin and ß-endorphin at picomolar levels in real time.


Assuntos
Grafite/química , Proteínas Imobilizadas/química , Microeletrodos , Peptídeos Opioides/análise , Receptores Opioides mu/química , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Ala(2)-MePhe(4)-Gly(5)-Encefalina/química , Humanos , Polimetil Metacrilato/química , Termodinâmica , beta-Endorfina/química
15.
Biomed Environ Sci ; 31(12): 876-882, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30636657

RESUMO

OBJECTIVE: To determine the mitigating effects of sodium 4-phenylbutyrate (4-PBA) on high-fat diet (HFD)-induced spermatogenesis dysfunction. METHODS: Male rats (n = 30) were randomly divided into three groups: control, HFD, and 4-PBA (HFD +4-PBA). After 13 weeks, rats were euthanized. Testes and epididymis were harvested for further analysis. Sex hormones were detected, and hematoxylin and eosin staining was performed to examine the histological changes in the testes. Semen samples were collected to evaluate sperm quality. Spermatogenic cell apoptosis was detected by TUNEL assay. RESULTS: Compared with the control group, the final body weight and body weight gain were significantly higher in HFD-fed rats, while the testicle/body weight ratios were lower (P < 0.05). In HFD-fed rats, obvious pathological changes in the testicular tissue were observed. Treatment with 4-PBA attenuated HFD-induced histological damage, ameliorated the HFD-induced decrease in serum testosterone (T), and reduced the rate of testicular cell apoptosis (P < 0.05) in obese male rats. Finally, 4-PBA significantly improved semen parameters in HFD rats (P < 0.05). CONCLUSION: HFD exposure induced detrimental effects on spermatogenesis, semen quality, serum T level, and testicular cell apoptosis in rats. Treatment with 4-PBA ameliorated HFD?induced impaired spermatogenesis via inhibition of apop-tosis in rats. 4-PBA may have therapeutic value in the treatment of obesity?related impairment of spermatogenesis.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Fenilbutiratos/farmacologia , Espermatogênese/efeitos dos fármacos , Animais , Masculino , Ratos Sprague-Dawley , Análise do Sêmen , Testículo/efeitos dos fármacos , Testículo/patologia , Testosterona/sangue
16.
Mol Med Rep ; 17(1): 1118-1124, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29115484

RESUMO

Levodopa (L­DOPA) is the gold standard for symptomatic treatment of Parkinson's disease (PD); however, long­term therapy is associated with the emergence of L­DOPA­induced dyskinesia (LID). Nigral dopaminergic cell loss determines the degree of drug exposure and time required for the initial onset of LID. Accumulating evidence indicates that α­lipoic acid (ALA) decreases this nigral dopaminergic cell loss. However, until now, the precise mechanisms of ALA have only been partially understood in LID. Chronic L­DOPA treatment was demonstrated to develop intense AIM scores to assess dyskinetic symptoms. Rats in the LID group were administrated twice daily with L­DOPA + benserazide for 3 weeks to induce a rat model of dyskinesia. Moreover, other 6­OHDA­lesioned rats were treatment with ALA (31.5 mg/kg or 63 mg/kg) in combination with L­DOPA treatment. Furthermore, the authors investigated the level of malondialdehyde (MDA) and glutathione (GSH) activity, as well as IBa­1, caspase­3 and poly (ADP-ribose) polymerase (PARP) in substantia nigra by the way of western blotting and immunofluorescence. ALA reduced LID in a dose­dependent manner without compromising the anti­PD effect of L­DOPA. Moreover, ALA reduced the level of MDA and upregulated the GSH activity, as well as ameliorated IBa­1 positive neurons in the substantia nigra. Finally, it was identified that ALA could reduce L­DOPA­induced cleaved­caspase­3 and PARP overexpression in the substantia nigra. Based on the present findings, ALA could be recommended as a promising disease­modifying therapy when administered with L­DOPA early in the course of PD. The exact mechanism for this action, although incompletely understood, appears to relate to anti­oxidative stress and anti­apoptosis.


Assuntos
Antioxidantes/farmacologia , Discinesia Induzida por Medicamentos , Levodopa/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Ácido Tióctico/farmacologia , Animais , Caspase 3/metabolismo , Modelos Animais de Doenças , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Feminino , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/prevenção & controle , Poli(ADP-Ribose) Polimerases/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Substância Negra/metabolismo
17.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 33(11): 1467-1471, 2017 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-29268848

RESUMO

Objective To investigate the effects of paeoniflorin (PF) on liver injury of MRL/lpr mice and its underlying mechanisms. Methods The research included 10 normal control C57BL/6 mice and 40 MRL/lpr mice. MRL/lpr mice were randomly assigned equally to a blank control group, a dexamethasone (1.5 mg/kg) group, and two PF (20, 40 mg/kg) groups. The serum levels of alanine transaminase (ALT) and aspartate transaminase (AST) were tested with microplate assay. Inflammatory cytokines in the serum and liver were also detected using ELISA. Liver pathological changes were observed using HE staining. The protein levels of receptor interacting protein140 (RIP140), Toll-like receptor 4 (TLR4), p-NF-κBp65, NF-κBp65, p-IκBα and IκBα in the liver were detected by Western blot analysis. Results PF significantly decreased the serum levels of AST and ALT, obviously decreased the expressions of the inflammatory cytokines IL-1ß, IL-6 and TNF-α in the serum and liver, alleviated liver pathological changes and inhibited the expressions of RIP140, TLR4, p-NF-κBp65, p-IκBα proteins in the MRL/lpr mice. Conclusion PF has protective effects against liver injury in MRL/lpr mice by inhibiting NF-κB pathway.


Assuntos
Glucosídeos/farmacologia , Fígado/efeitos dos fármacos , Monoterpenos/farmacologia , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Aspartato Aminotransferases/sangue , Citocinas/sangue , Citocinas/metabolismo , Feminino , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos MRL lpr , Fitoterapia , Distribuição Aleatória , Receptor 4 Toll-Like/metabolismo
18.
Hum Mutat ; 38(12): 1740-1750, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28887846

RESUMO

Leukoencephalopathies are a broad class of common neurologic deterioration for which the etiology remains unsolved in many cases. In a Chinese Han family segregated with sensorineural hearing loss and leukoencephalopathy, candidate pathogenic variants were identified by targeted next-generation sequencing of 144 genes associated with deafness and 108 genes with leukoencephalopathy. Novel compound heterozygous mutations p.R477H and p.P505S were identified in KARS, which encodes lysyl-tRNA synthetase (LysRS), as the only candidate causative variants. These two mutations were functionally characterized by enzymatic assays, immunofluorescence, circular dichroism analysis, and gel filtration chromatography. Despite no alteration in the dimer-tetramer oligomerization and cellular distribution by either mutation, the protein structure was notably influenced by the R477H mutation, which subsequently released the protein from the multiple-synthetase complex (MSC). Mutant LysRSs with the R477H and P505S mutations had decreased tRNALys aminoacylation and displayed a cumulative effect when introduced simultaneously. Our studies showed that mutations in KARS lead to a newly defined subtype of leukoencephalopathy associated with sensorineural hearing impairment. The combined effect of reduced aminoacylation and release of LysRS from the MSC likely underlies the pathogenesis of the KARS mutations identified in this study.


Assuntos
Surdez/genética , Perda Auditiva Neurossensorial/genética , Leucoencefalopatias/genética , Lisina-tRNA Ligase/genética , Adulto , Substituição de Aminoácidos , Aminoacilação/genética , Grupo com Ancestrais do Continente Asiático , Encéfalo/diagnóstico por imagem , Surdez/complicações , Surdez/diagnóstico por imagem , Surdez/enzimologia , Feminino , Perda Auditiva Neurossensorial/complicações , Perda Auditiva Neurossensorial/diagnóstico por imagem , Perda Auditiva Neurossensorial/enzimologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Leucoencefalopatias/complicações , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/enzimologia , Lisina-tRNA Ligase/metabolismo , Imagem por Ressonância Magnética , Masculino , Modelos Moleculares , Mutação , Fenótipo , Análise de Sequência de DNA , Espectrometria de Massas em Tandem , Adulto Jovem
19.
Front Cell Neurosci ; 11: 79, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28377695

RESUMO

Our previous study showed that Schwann cells (SCs) promote survival, proliferation and migration of co-transplanted oligodendrocyte progenitor cells (OPCs) and neurological recovery in rats with spinal cord injury (SCI). A subsequent in vitro study confirmed that SCs modulated OPC proliferation and migration by secreting platelet-derived growth factor (PDGF)-AA and fibroblast growth factor-2 (FGF)-2. We also found that PDGF-AA stimulated OPC proliferation and their differentiation into oligodendrocytes (OLs) at later stages. We therefore speculated that PDGF-AA administration can exert the same effect as SC co-transplantation in SCI repair. To test this hypothesis, in this study we investigated the effect of transplanting PDGF-AA-overexpressing OPCs in a rat model of SCI. We found that PDGF-AA overexpression in OPCs promoted their survival, proliferation, and migration and differentiation into OLs in vivo. OPCs overexpressing PDGF-AA were also associated with increased myelination and tissue repair after SCI, leading to the recovery of neurological function. These results indicate that PDGF-AA-overexpressing OPCs may be an effective treatment for SCI.

20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 42(3): 251-256, 2017 Mar 28.
Artigo em Chinês | MEDLINE | ID: mdl-28364096

RESUMO

OBJECTIVE: To evaluate the effects of dexamethasone on systemic lupus erythematosus complicated with cognitive dysfunction.
 Methods: Ten wild type mice and 20 MRL/lpr mice were applied for the research. MRL/lpr mice were randomly assigned to a MRL/lpr group and a MRL/lpr + dexamethasone (1.5 mg/kg) group. Interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor alpha (TNF-α) in serum and hippocampus were detected. The protein phosphorylation levels of phosphoinositide 3-kinase (P-PI3K), protein kinase B (P-Akt), NF-kappa-B inhibitor alpha (P-IκBa) and nuclear transcription factor kappa-B p65 (P-NF-κB p65) were detected by Western blot, the level of P-NF-κB p65 also was detected by immunohistochemistry. 
 Results: Treatment with dexamethasone (1.5 mg/kg) alleviated the cognitive dysfunction and decreased the levels of IL-6, IL-1ß and TNF-α in serum and hippocampus, and reduced the levels of P-PI3K, P-Akt, P-IκBa and P-NF-κB p65 in hippocampus in MRL/lpr mice.
 Conclusion: Dexamethasone may play a protective role in the cognitive function by decreasing the levels of TNF-α and IL-1ß in the hippocampus of MRL/lpr lupus mice.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Animais , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Hipocampo/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/metabolismo , Camundongos , Camundongos Endogâmicos MRL lpr , Inibidor de NF-kappaB alfa/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Distribuição Aleatória , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
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