Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.156
Filtrar
1.
Insect Sci ; 27(1): 14-21, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31246335

RESUMO

Manipulating an exogenous or endogenous gene of interest at a defined level is critical for a wide variety of experiments. The Gal4/UAS system has been widely used to direct gene expression for studying complex genetic and biological problems in Drosophila melanogaster and other model organisms. Driven by a given tissue-specific Gal4, expressing UAS-transgene or UAS-RNAi (RNA interference) could be used to up- or down-regulate target gene expression, respectively. However, the efficiency of the Gal4/UAS system is roughly predefined by properties of transposon vector constructs and the insertion site in the transgenic stock. Here, we describe a simple way to modulate optomotor blind (omb) expression levels in its endogenous expression region of the wing disc. We co-expressed UAS-omb and UAS-omb-RNAi together under the control of dpp-Gal4 driver which is expressed in the omb expression region of the wing pouch. The repression effect is more sensitive to temperature than that of overexpression. At low temperature, overexpression plays a dominant role but the efficiency is attenuated by UAS-omb-RNAi. In contrast, at high temperature RNAi predominates in gene expression regulation. By this strategy, we could manipulate omb expression levels at a moderate level. It allows us to manipulate omb expression levels in the same tissue between overexpression and repression at different stages by temperature control.

2.
Arch Insect Biochem Physiol ; : e21639, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31647582

RESUMO

Carbon dioxide (CO2 ) exposure is a common method of anesthesia in studies of Drosophila melanogaster. A number of negative side effects of CO2 anesthesia have been reported. It is not clear whether the length of CO2 anesthesia time affects Drosophila survival in aging research. Here, we examined the potential effect of the CO2 anesthesia time length of 10-150 min. We found that long CO2 exposure could lead to Drosophila death, more significant in males. The longer the anesthesia time is, the longer it takes for flies to wake up. Long-time CO2 anesthesia can reduce the lifespan. Our stress tests showed that long-time CO2 anesthesia can increase the average survival time in both males and females under starvation conditions, but can only increase female lifespan under H2 O2 oxidative stress. Long-time CO2 anesthesia also significantly affects physiological traits, with spontaneous activity increased in females but decreased in males, and reduced female fecundity. Our study suggests that limiting the CO2 anesthesia time and giving enough recovery time before performing physiological tests are important in Drosophila aging research.

3.
J Control Release ; 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31654687

RESUMO

Development of IVIVCs is a very complicated process, especially for complex drug products such as parenteral PLGA microspheres with multiphasic drug release characteristics. Specifically, microspheres that exhibit an initial burst release phase are even more challenging since the in vitro and in vivo burst release phases may not be comparable if drug absorption is rate-limiting at this stage. Therefore, the objectives of the present work were: 1) to investigate the predictability of developed IVIVCs for the in vivo burst release phase based on the in vitro burst release phase of the formulations; and 2) to evaluate the impact of variable burst release on the predictability of the developed IVIVCs for two different types of microsphere-based drug products. Accordingly, Risperdal Consta® (Risperidone) and Lupron Depot® (Leuprolide acetate, LA) were selected as model products. Compositionally equivalent risperidone and LA formulations with variable burst release phases were prepared with manufacturing process changes (such as solvent systems and mixing methods). The prepared microspheres exhibited differences in critical physicochemical properties (such as particle size, porosity, average pore diameter, and drug distribution) and hence differences in their in vitro release characteristics (such as variable burst release and release rate). The in vitro and in vivo (rabbit model (intramuscular injection) burst release were similar for the risperidone microspheres but were significantly different for the LA microspheres. This had an impact on the complexity of the developed IVIVC models. Level A IVIVCs with the ability to predict various types of burst release were developed using time scaling and shifting factors. Moreover, it was observed that IVIVCs developed using formulations with less variation in burst release had better predictability and vice-versa. Thus, the present research has provided a comprehensive understanding of the impact of the burst release phase on the development, complexity, and predictability of IVIVCs for complex parenteral microspheres containing a variety of therapeutic molecules.

4.
Medicine (Baltimore) ; 98(38): e17241, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567989

RESUMO

BACKGROUND: Previous studies have reported that physical therapy (PT) can be used for the treatment of chronic obstructive pulmonary disease (COPD). However, its effectiveness is still inconclusive. This systematic review will aim to assess its effectiveness and safety for the treatment of patients with COPD. METHODS: All randomized controlled trials (RCTs) literatures of PT for COPD will be searched from the databases of Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDILINE, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Information, and Wanfang Data from inception to the present without any language restrictions. Two reviewers will independently perform the study selection, data extraction, and methodological quality assessment. A third reviewer will be invited to resolve any disagreements occurred between 2 reviewers. RESULTS: The primary outcome is lung function. The secondary outcomes include symptoms, health-related quality of life, mortality, and adverse events. The outcome data will be pooled by using the models of random-effects or fixed-effects according to the detected heterogeneity. CONCLUSION: The findings of this study will provide up-todated summary evidence for assessing the effectiveness and safety of PT for COPD.


Assuntos
Modalidades de Fisioterapia , Doença Pulmonar Obstrutiva Crônica/terapia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
5.
Respir Res ; 20(1): 161, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31590675

RESUMO

BACKGROUND: There is growing literature suggesting a link between vitamin D and asthma lung function, but the results from systematic reviews are conflicting. We conducted this meta-analysis to investigate the relation between serum vitamin D and lung function in asthma patients. METHODS: Major databases, including OVID, MEDLINE, Web of Science and PUBMED, were searched until 10th October 2018. All published observational studies related to vitamin D and asthma were extracted. All meta-analyses were performed using Review Manager 5.3.5. RESULTS: This quantitative synthesis found that asthma patients with low vitamin D levels had lower forced expiratory volume In 1 s (FEV1) (mean difference (MD) = - 0.1, 95% CI = - 0.11 to - 0.08,p < 0.01;I2 = 49%, p = 0.12) and FEV1% (MD = - 10.02, 95% CI = - 11 to - 9.04, p < 0.01; I2 = 0%, p = 0.82) than those with sufficient vitamin D levels. A positive relation was found between vitamin D and FEV1 (r = 0.12, 95% CI = 0.04 to 0.2, p = 0.003; I2 = 59%,p = 0.01), FEV1% (r = 0.19, 95% CI = 0.13 to 0.26, p < 0.001; I2 = 42%, p = 0.11), forced vital capacity (FVC) (r = 0.17, 95% CI = 0.00 to 0.34, p = 0.05; I2 = 60%, p = 0.04), FEV1/FVC (r = 0.4, 95% CI = 0.3 to 0.51, p < 0.001; I2 = 48%, p = 0.07), and the asthma control test (ACT) (r = 0.33, 95% CI = 0.2 to 0.47, p < 0.001; I2 = 0%, p = 0.7). Subgroup analysis indicated that the positive correlation between vitamin D and lung function remained significant in both children and adults. CONCLUSIONS: Our meta-analysis suggested that serum vitamin D levels may be positively correlated with lung function in asthma patients. Future comprehensive studies are required to confirm these relations and to elucidate potential mechanisms.

6.
Ann Palliat Med ; 8(4): 469-475, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31594375

RESUMO

BACKGROUND: This study aimed to investigate the effects of dexmedetomidine on the post-operative recovery and mental status in patients receiving robotic-assisted thoracic surgery (RATS). METHODS: One hundred patients who received selective RATS under general anesthesia were recruited and assigned into control group (C) and dexmedetomidine group (D). The anesthesia induction and maintenance were consistent between groups. Midazolam, sufentanil, propofol and rocuronium were intravenously injected for anesthesia induction, followed by mechanical ventilation after endotracheal intubation. Sevoflurane inhalation at a minimum alveolar concentration (MAC) of 0.5 was administered, propofol and remifentanil were intravenously injected to maintain the bispectral index (BIS) at 40-60, and rocuronium was intravenously injected once every 30 min. In the D group, dexmedetomidine was intravenously injected after endotracheal intubation, and then it was injected before the end of surgery. In the C group, normal saline of equal volume was injected. The hemodynamic parameters, blood loss, urine volume, time of surgery, time of anesthesia, total dose of propofol, time of thoracic tube indwelling, hospital stay and pulmonary complications were recorded; blood gas analysis was performed after extubation; the QoR-15 and mini-mental state examination (MMSE) questionnaires were employed for the assessment of mental status at 1 and 3 days after surgery. RESULTS: The mean arterial pressure (MAP), heart rate (HR) and brain oxygenation were similar between groups at different time points (P>0.05). There were no significant differences in the operation time, time of anesthesia and intra-operative urine volume between groups. As compared to the C group, the blood loss and dose of propofol reduced significantly (P<0.05). After extubation, the respiratory frequency reduced and PaO2 increased markedly (P<0.05). After surgery, the time of thoracic tube indwelling and hospital stay reduced dramatically in the D group as compared to the C group (P<0.05). The QoR-15 score and MMSE score in the D group were markedly higher than in the C group (P<0.05). CONCLUSIONS: Dexmedetomidine can improve the post-operative recovery and mental status after RATS.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31584221

RESUMO

Protein channels are characterized by high transport selectivity essential for maintaining proper cellular functions. Extensive efforts over the past four decades to recapitulate such high selectivity have not been very successfully. In this work, we report a novel series of aromatic foldamer-based polymeric channels, with the backbone stabilized by differential electrostatic repulsions among heteroatoms helically arrayed along in the helical backbone. Possessing a hydrophilic electron-rich hollow cavity of 3 Å in diameter, nanotubes of 2.3 and 2.7 nm in average length mediate highly efficient transport of K + ions, with exceptionally high K + /Na + selectivity values of 16.3 and 12.6, respectively.

8.
Br J Cancer ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31570753

RESUMO

BACKGROUND: The extracellular matrix (ECM) is essential for malignant tumour progression, as it is a physical barrier to various kinds of anticancer therapies. Matrix metalloproteinase (MMPs) can degrade almost all ECM components, and macrophages are an important source of MMPs. Studies using macrophages to treat tumours have shown that macrophages can enter tumour tissue to play a regulatory role. METHODS: We modified macrophages with a designed chimeric antigen receptor (CAR), which could be activated after recognition of the tumour antigen HER2 to trigger the internal signalling of CD147 and increase the expression of MMPs. RESULTS: Although CAR-147 macrophage treatment did not affect tumour cell growth in vitro compared with control treatment. However, we found that the infusion of CAR-147 macrophages significantly inhibited HER2-4T1 tumour growth in BALB/c mice. Further investigation showed that CAR-147 macrophages could reduce tumour collagen deposition and promote T-cell infiltration into tumours, which were consistent with expectations. Interestingly, the levels of the inflammatory cytokines TNF-α and IL-6, which are key factors in cytokine release syndrome, were significantly decreased in the peripheral blood in CAR-147 macrophage-transfused mice. CONCLUSION: Our data suggest that targeting the ECM by engineered macrophages would be an effective treatment strategy for solid tumours.

9.
Int Urol Nephrol ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31571158

RESUMO

PURPOSE: The number of examined lymph node (ELN) is regarded as the critical quality index for cancer care. We scrutinize the relationship among ELN number, accurate staging, and long-term survival in prostate cancer (Pca). METHODS: Population-based data on Pca patients in 2004-2015 from the US SEER database were investigated. The connection among ELN number and stage migration, overall survival (OS), and prostate cancer-specific survival (CSS) were evaluated by performing multivariable-adjusted logistic, Cox proportional hazards, and fine-gray competing-risk regression models, respectively. LOWESS smoother was used to fit the series of ELN number, odds ratios (OR), and hazard ratios (HR), while the Chow test was used to resolve the structural breakpoints. Subgroup and interaction analyses were performed in different risk populations. RESULTS: Overall, 84,838 patients were analyzed. Serial improvements were seen in stage migration (OR, 1.072, P < 0.001), OS (HR, 0.991; P < 0.001), and CSS (HR, 0.983; P < 0.001) per additional ELN after adjusting for confounders. Subgroup analysis revealed that the ELN number gains the most staging and survival benefits in high-risk population (P for interaction < 0.001). Cut-point analyses suggested that an optimal number of 12 ELNs, which was verified by the cumulative incidence curve, had a strong capability to distinguish different probabilities of CSS. CONCLUSIONS: Higher quantities of ELNs are related to more-accurate nodal staging and long-term survival of Pca patients undergoing RP. We highlight that 12 ELNs are the optimal cut-point for the high-risk population to investigate the quality of LN detection and stratifying postoperative prognosis.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31564529

RESUMO

BACKGROUND: To evaluate and compare the results of three different cervical cancer screening strategies including cytology screening, HR-HPV screening which taking HR-HPV testing as primary test and co-testing which taking both tests at the same time, then provide evidence to explore whether the cervical cancer screening can be conducted in community healthcare centers in Beijing. METHODS: 182,119 women aged between 35 and 64, who were screened in the primary healthcare facilities of nine districts in Beijing from January 2014 to March 2015, were enrolled in this study. Cytology screening was performed in participants during January 2014 and December 2014 as a conventional arm. HR-HPV screening strategy and co-testing were randomly allocated to participants on districts level as experimental arm 1 and 2 during January 2015 and March 2015. Cervical Intraepithelial Neoplasia grade 2 or worse (CIN 2+) was defined as endpoint. The screening results and costs to detect a case of three strategies were calculated. RESULTS: The positivity rate, colposcopy referral rate and biopsy referral rate of co-testing were 8.46%, 6.36% and 4.65% respectively, which were all significantly higher than the other two screening strategies. The detection rate of CIN 2+ by co-testing was 5.06‰ and was much more than the other two screening strategies, while the HR-HPV screening had the highest PPV of 14.40%. The HR-HPV screening ignores some lesion which can be found by co-testing. Co-testing refers a woman to colposcopy with a positive screening result at the least cost, but it costs the most to detect a CIN 2+ case. CONCLUSIONS: To detect more cases of CIN 2+, co-testing performs better although with the most cost. And the primary healthcare facilities in Beijing have the capability to carry out the cervical cancer screen programs and prompts women with positive screen results to the hospital.

11.
Neurochem Int ; 131: 104567, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31586590

RESUMO

P2Y purinergic receptors expressed in neurons and satellite glial cells (SGCs) of the trigeminal ganglion (TG) contribute to inflammatory and neuropathic pain. P2Y14 receptor expression is reported in the spinal cord, dorsal root ganglion (DRG), and TG. In present study, the role of P2Y14 receptor in the TG in inflammatory orofacial pain of Sprague-Dawley (SD) rats was investigated. Peripheral injection of complete Freund's adjuvant (CFA) induced mechanical hyperalgesia with the rapid upregulation of P2Y14 receptor, glial fibrillary acidic protein (GFAP), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), C-C chemokine CCL2, phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), and phosphorylated p38 (p-p38) proteins in the TG. Furthermore, immunofluorescence staining confirmed the CFA-induced upregulation of P2Y14 receptor. Double immunostaining showed that P2Y14 receptor colocalized with glutamine synthetase (GS) and neuronal nuclei (NeuN). Finally, trigeminal injection of a selective antagonist (PPTN) of P2Y14 receptor attenuated CFA-induced mechanical hyperalgesia. PPTN also decreased the upregulation of the GFAP, IL-1ß, TNF-α, CCL2, p-ERK1/2, and p-p38 proteins. Our findings showed that P2Y14 receptor in TG may contribute to orofacial inflammatory pain via regulating SGCs activation, releasing cytokines (IL-1ß, TNF-α, and CCL2), and phosphorylating ERK1/2 and p38.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31576591

RESUMO

OBJECTIVES: To develop child- and parent-reported toolkits for active caries and caries experience in children and adolescents, ages 8-17. METHODS: A sample of 398 child/parent dyads recruited from 12 dental practices in Los Angeles County completed a computer-assisted survey that assessed oral health perceptions. In addition, children received a dental examination that identified the presence or absence of active caries and caries experience. A Multiple Adaptive Regression Splines model was used to identify a subset of survey items associated with active caries and caries experience. The splines and coefficients were refined by generalized cross-validation. Sensitivity and specificity for both dependent variables were evaluated. RESULTS: Eleven child self-reported items were identified that had sensitivity of 0.82 and specificity of 0.45 relative to active caries. Twelve parent-reported items had a sensitivity of 0.86 and specificity of 0.50. Seven child self-reported items had a sensitivity of 0.86 and specificity of 0.34, and 11 parent-reported items had a sensitivity of 0.86 and specificity of 0.47 for caries experience. CONCLUSIONS: The survey items identified here are useful in distinguishing children with and without active caries and with and without caries experience. This research presents a path towards using children's and their parents' reports about oral health to screen for clinically determined caries and caries exposure. The items identified in this study can be useful when clinical information is unavailable.

14.
BMC Surg ; 19(1): 142, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601219

RESUMO

BACKGROUND: Eccrine porocarcinoma is an extremely rare skin adnexal malignant neoplasia with highly invasive and metastatic potential. We report an additional case of eccrine porocarcinoma with intracranial metastases. This case is characterized by a complete record of the progress of eccrine porocarcinoma, its immunohistochemistry after three operations showed a progressive increase in the level of Ki-67 index. CASE PRESENTATION: We herein report a case of a 37-year-old-male with eccrine carcinoma occurring on the left posterior occipital scalp which invaded the skull and dura, presenting with progressive headache. This patient has performed three surgeries in total. During the last hospitalization, he underwent an extended surgical resection, lymphadenectomy, myocutaneous flap transplantation and vascular anastomosis in our institution. After surgery, he was treating with radiotherapy at 200 Gray in 12 fractions. But one year after the operation, he developed chest tightness, imaging examination and biopsy puncture revealed pulmonary metastasis. CONCLUSION: Intracranial metastasis of eccrine porocarcinoma is a late event with poor prognosis. This case emphases on that progressively increased level of Ki-67 index may predict more chance to occur the intracranial metastasis of scalp eccrine porocarcinoma, long-term follow-up and appropriately dense follow-up interval is necessary.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31581074

RESUMO

Natural human-computer interaction and audio-visual human behaviour sensing systems, which would achieve robust performance in-the-wild are more needed than ever as digital devices are becoming indispensable part of our life more and more. Accurately annotated real-world data are the crux in devising such systems. However, existing databases usually consider controlled settings, low demographic variability, and a single task. In this paper, we introduce the SEWA database of more than 2000 minutes of audio-visual data of 398 people coming from six cultures, 50% female, and uniformly spanning the age range of 18 to 65 years old. Subjects were recorded in two different contexts: while watching adverts and while discussing adverts in a video chat. The database includes rich annotations of the recordings in terms of facial landmarks, facial action units (FAU), various vocalisations, mirroring, and continuously valued valence, arousal, liking, agreement, and prototypic examples of (dis)liking. This database aims to be an extremely valuable resource for researchers in affective computing and automatic human sensing and is expected to push forward the research in human behaviour analysis, including cultural studies. Along with the database, we provide extensive baseline experiments for automatic FAU detection and automatic valence, arousal and (dis)liking intensity estimation.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31516025

RESUMO

We investigated the use of a system with an ingestible sensor (Proteus Digital Health Feedback system) coencapsulated with antiretrovirals (ARVs) to measure real-time adherence. To assess the safety and impact, if any, coencapsulation might have on ARV concentrations, we evaluated the pharmacokinetics of ARVs coencapsulated with an ingestible sensor for eight commonly used fixed-dose combination ARVs: emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF); FTC/tenofovir alafenamide (TAF); efavirenz (EFV)/FTC/TDF; abacavir (ABC)/lamivudine (3TC); dolutegravir (DTG)/ABC/3TC; rilpivirine (RPV)/TAF/FTC; elvitegravir (EVG)/cobicistat (COBI)/FTC/TAF; and bictegravir (BIC)/FTC/TAF. The steady-state apparent peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) were determined from plasma concentrations measured at predose, 1, 2, 4, and 6 h postdose, and compared with literature values. A total of 49 unique patients on stable regimens for at least 12 weeks with undetectable viral loads were recruited. Cmax and AUC values were not statistically significantly different from literature values for all of the formulations except the Cmax of FTC/TDF, Cmax of BIC, and the Cmax of RPV. In a subsequent evaluation of FTC/TDF and BIC/FTC/TAF using a crossover design, the geometric mean ratio (GMR) between the coencapsulated and the unencapsulated formulations for FTC/TDF were the following: FTC, 84.6% (90% confidence interval [CI] 66.6-107.4) for AUC and 77.5% (60.1-99.9) for Cmax. For tenofovir (TFV), the GMR was 96.2% (90% CI 89.2-103.8) for AUC and 87.3% (64.2-118.7) for Cmax. The GMR for BIC (from the BIC/FTC/TAF formulation) was 98.0% (90% CI 84.5-113.5) for AUC and 89.9% (84.5-95.7) for Cmax. The observed deviation in FTC/TDF (Truvada) may be due to participant characteristics, fasted/fed conditions, and/or random variation and may warrant further investigations with a larger sample size. These findings provide assurance for use of coencapsulated ARVs for future HIV treatment-adherence research.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31500322

RESUMO

Due to the widespread use of bisphenol analogues (BPs) as alternatives to bisphenol A (BPA), considerable attention for health risk has been shown in aquatic ecosystems. The occurrence and distribution of six BPs were researched in a soluble phase (<10-3 µm), colloidal phase (10-3 µm to 1 µm), and suspended particulate matter (SPM >1 µm) in a water diversion project of Nanjing, China. Except for bisphenol Z, all BPs were detected in two or three phases, where the total concentrations of detected BPs were 161-613 ng/L, 5.19-77.2 ng/L, and 47.5-353 ng/g for the soluble phase, colloidal phase, and SPM, respectively. Among the detected compounds, BPA is still the dominant BPs in the soluble and colloidal phases, which is followed by bisphenol-S , while bisphenol-AF was the major contaminant in SPM, followed by BPA. The mean contribution proportions of colloids were 1-2 orders of magnitude higher than SPM, which suggests that colloids have a clear impact on regulating BPs' environmental behaviors. In terms of spatial distribution, the water diversion project could reduce the pollution levels of BPs, which might further affect the ecological security of the Yangtze River.

18.
Neuropharmacology ; 160: 107779, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31539536

RESUMO

Depression is considered a neuropsychiatric condition which is associated with neuronal injury within specific brain regions. We previously reported that cyclo-oxygenase (COX)-2, a rate-limiting enzyme for prostaglandin E2 (PGE2) synthesis, significantly enhanced depressive-like disorders induced by chronic stress in rats. However, the underlying molecular mechanisms and identification of potential therapeutic targets for preventing neuronal injury associated with depression remain largely uncharacterized. Here, we show that COX-2 inhibition by celecoxib protects against neuronal injury through suppression of oxidative stress and, in this way, mediates its antidepressant effects. COX-2 is highly expressed in the hippocampal dentate gyrus (DG) of rat depression model and its activity is responsible for depression-like behaviors as demonstrated in two independent rat models of depression. Inhibition of COX-2 exerts neuroprotective actions in DG regions, including suppressing neuroinflammatory response, against oxidative stress and neuronal apoptosis, which are the critical risk factors for neuronal injury and pathophysiology of depression. Moreover, the antioxidant, N-acetylcysteine (NAC), significantly attenuates oxidative stress levels and dendritic spine deficiencies resulting from COX-2 overexpression; and, suppression of oxidative stress by NAC also significantly ameliorates depressive behaviors in rats. These findings suggest that selective inhibition of COX-2 ameliorates depression-like behaviors in rat models of depression. This selective inhibition of COX-2 appears to be protective against oxidative stress and neuronal deterioration resulting from chronic stress. Taken together, these findings have potentially important clinical implications with regard to the development of novel therapeutic approaches in the treatment of neuropsychiatric conditions like depression.

19.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(4): 548-555, 2019 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-31484620

RESUMO

Leukemia is a disease featured by the malignant proliferation of hematopoietic stem cells or progenitor cells in the blood system.While chemotherapy remains its mainstream treatment,disease relapse and drug resistance are still challenging problems.As one of the epigenetic mechanisms,histone methylation is involved in cell proliferation,differentiation,and apoptosis by regulating gene transcription.Recent studies have found that the histone demethylase lysine-specific demethylase 6A(KDM6A),also known as ubiquitously transcribed tetratricopeptide repeat on chromosome X(UTX),is closely related to the occurrence of a variety of tumors,especially leukemia.KDM6A activates gene expression by demethylating H3K27me3 to H3K27me2 or H3K27me1.Besides,KDM6A can regulate the activation of the target gene transcription through its non-demethylase functions.It can serve as the subunit of complex of proteins associated with Set1,thus getting involved in the regulation of H3K4me1.It can be combined with yeast mating type conversion/sucrose unfermented complex family to promote the formation of an open chromatin conformation.Finally,it can promote the production of H3K27ac.This article reviews the recent studies on the structure and biological activity of histone demethylase KDM6A(UTX)and its role in treating leukemia,thus providing a new research direction for targeted treatment of leukemia.


Assuntos
Epigênese Genética , Histona Desmetilases/metabolismo , Leucemia/enzimologia , Lisina , Proteínas Nucleares/metabolismo , Histonas , Humanos , Leucemia/terapia
20.
Hum Immunol ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31521393

RESUMO

Chronic kidney disease (CKD) is becoming a global public health problem and usually cause End-Stage Renal Disease (ESRD) in the end of progression. To analyze the associations of HLA-A, -B, -C, -DRB1 and -DQB1 alleles at high resolution with ESRD in Jiangsu province of China, a total of 499 unrelated patients with ESRD from the First Affiliated Hospital with Nanjing Medical University and 1584 healthy controls from Jiangsu Branch of Chinese Marrow Donor Program (CMDP) were genotyped at HLA-A, -B, -C, -DRB1 and -DQB1 loci. Statistical analysis was applied to compare the differences of HLA allele frequencies between patients with ESRD and healthy controls. As results, no protective allele at A locus was found and the susceptible alleles were A*11:01 and A*31:01. At B locus, B*15:01, B*55:02 and B*39:05 emerged as susceptible alleles, whereas no protective allele was found. At C locus, C*06:02 and C*07:01 emerged as protective alleles and no susceptible allele was found. At DRB1 locus, six alleles including DRB1*03:01, DRB1*04:03, DRB1*04:04, DRB1*04:05, DRB1*11:01 and DRB1*12:02 emerged as susceptible alleles, while DRB1*15:01 emerged as a protective allele. At DQB1 locus, DQB1*02:01, DQB1*03:01, DQB1*03:02 and DQB1*04:01 emerged as susceptible alleles, while DQB1*06:02 and DQB1*06:09 emerged as protective alleles. Haplotype A*11:01-C*03:03-B*15:01-DRB1*11:01-DQB1*03:01 containing four susceptible alleles was regarded as the most susceptible haplotype. The susceptible alleles and haplotypes might be used as some important risk classification markers. Besides, in the consanguineous renal transplantation, it would be very beneficial for the long-term survival of renal transplant patients to avoid the susceptible alleles and haplotypes in selecting optimal donors.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA