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1.
Lasers Med Sci ; 2019 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-31446581

RESUMO

Based on two separate randomized controlled trials (RCTs) on traditional Chinese medicine (TCM) moxibustion and 10.6-µm infrared laser moxibustion in treating knee osteoarthritis (OA), we did an indirect and preliminary comparison of the effects of the 10.6-µm laser moxibustion with the traditional moxibustion for knee osteoarthritis. The objective was to see whether the laser moxibustion is non-inferior to the traditional moxibustion in alleviating symptoms of knee osteoarthritis such as pain, stiffness, and joint dysfunction as well as improving quality of life for the patients with knee osteoarthritis, and whether a further RCT directly comparing the laser and traditional moxibustion is necessary. Pooled data from two RCTs in patients with knee osteoarthritis, trial ISRCTN68475405 and trial ISRCTN26065334, were used. In the two RCTs, the eligibility criteria were almost identical, the treatment procedure (i.e., sessions, duration, and points) were similar, and the outcome measurements (i.e., WOMAC for symptoms and SF-36 for quality of life) were the same. The double robustness method was used for the WOMAC scale and the SF-36 endpoints to detect the difference between traditional and laser moxibustion. The analysis comprised 55 patients from ISRCTN68475405 in real moxibustion arm (moxibustion group) and 88 patients from ISRCTN26065334 in real laser moxibustion arm (laser group). Demographic characteristics and course of disease were similar between the two groups. Causal inference, using the doubly robust estimating approach to correct for bias due to baseline differences, showed that there was no statistically significant difference in the WOMAC pain, stiffness, and physical function between the two treatments at midterm, end of treatment, and 4 weeks after the end of treatment (P > 0.05). The exception was that there was statistically significantly more benefit associated with laser moxibustion compared with traditional moxibustion in physical function at the follow-up of 4 weeks after the end of treatment (P=0.006). There was no statistically significant difference in most SF-36 endpoints (P > 0.05) except that physical functioning (PF), mental health (MH), and bodily pain (BP) were statistically significantly better in the laser group than in the traditional moxibustion group at the follow-up of 4 weeks after the end of treatment (P = 0.005, 0.034, 0.002). The benefits of 10.6-µm infrared laser moxibustion and the traditional moxibustion for knee osteoarthritis were comparable in pain, stiffness, physical dysfunction, and in most of the quality of life subdimensions. The laser moxibustion might be more beneficial in terms of physical function, body pain, and mental health in the long term. RCTs directly comparing 10.6-µm laser moxibustion with traditional moxibustion are warranted.

2.
BMJ Open ; 9(8): e029194, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31439605

RESUMO

INTRODUCTION: Neck pain (NP) is a common condition that can be effectively treated by acupuncture. However, several treatment point prescriptions (ie, local acupoints, distal acupoints, and sensitised acupoints) may be used. The present study aims to identify the types of sensitisation and the distribution of sensitised points in patients with NP, to analyse the cut-off values and sensitisation rate for acupoint sensitisation, and to summarise the dominant forms of optimally sensitised points. This information will be helpful when choosing the optimal points to treat NP. METHODS AND ANALYSIS: This multicentre, matched, case-control study will enrol 224 patients with NP, and 224 age-matched and sex-matched healthy participants as controls. Body surface temperature, mechanical pain threshold, pressure pain threshold and skin resistance will be assessed at the 15 acupoints most frequently used to treat NP, and at the five body regions in which pain occurs most frequently. Hypothesis testing will be used to compare the differences in variables between cases and controls. In addition, receiver operating characteristic curve analysis will be used to explore the cut-off values of the sensitive states of heat, pain and electrical resistance, which indicate sensitisation of the acupoint. The optimal points will be comprehensively determined by the acupoint sensitisation rate and OR. ETHICS AND DISSEMINATION: Ethical approval of this study has been granted by the Research Ethical Committee of the Teaching Hospital of Chengdu University of Traditional Chinese Medicine (ID: 2018 KL-016). The outcomes of the study will be disseminated through peer-reviewed publications. TRIAL REGISTRATION: ChiCTR1800016220.

3.
Medicine (Baltimore) ; 98(32): e16769, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393398

RESUMO

BACKGROUND: Postcholecystectomy syndrome (PCS) is a term used to describe the persistence of biliary colic or right upper quadrant abdominal pain with a variety of postoperative gastrointestinal symptoms. Acupuncture and related treatments have shown clinical effects for PCS in many studies. But the systematic reviews and meta-analyses for them are lacking. We aim to evaluate the efficacy and safety of acupuncture on the treatment of PCS. METHODS: We will search 8 electronic databases, including the Web of Science, PubMed, Cochrane Library, Embase, and 4 Chinese databases (CBM, Wanfang, VIP, and CNKI databases), and additional sources (WHO ICTRP, ChiCTR, Clinical Trials, Grey Literature Database), for potentially eligible studies. Literature retrieval, screening, and data extraction will be conducted by 2 researchers independently. In case of disagreement, a 3rd party shall be consulted to assist judgment. We will use RevmanV.5.3 to perform a fixed effect meta-analysis on the data of clinical homogeneity studies, and evidence's level will be assessed through the method for GRADE. RESULTS: This systematic review and meta-analysis will put a high-quality synthesis of the efficacy and safety of acupuncture treatment in PCS. CONCLUSION: The conclusion of this systematic review will provide evidence to assess acupuncture therapy is an efficacy and safe intervention to treat and control PCS. ETHICS AND DISSEMINATION: Since this article does not involve patients' private data, no ethical approval is required. The agreement will be disseminated by peer-reviewed journals or conference reports. TRIAL REGISTRATION NUMBER: PROSPERO CRD4201929287.


Assuntos
Terapia por Acupuntura/métodos , Síndrome Pós-Colecistectomia/terapia , Humanos , Projetos de Pesquisa
4.
Medicine (Baltimore) ; 98(34): e16882, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441863

RESUMO

BACKGROUND: Cancer-related fatigue (CRF) is the most common and distressing symptom associated with cancer treatment that breast cancer survivors (BCS) experience. We previously found that laser moxibustion may be efficacious for CRF. The primary aim of this study is to determine the specific efficacy of 10.6 µm infrared laser moxibustion on CRF. The secondary aim is to evaluate the effect of infrared laser moxibustion on co-existing symptoms that BCS experience. METHODS: We will conduct a randomized, sham-controlled, three-arm trial of infrared laser moxibustion (ILM) against sham ILM (SILM) and waitlist control (WLC) among BCS with moderate to severe fatigue. The two intervention groups will receive either real or sham infrared laser moxibustion on four acupoints (i.e., ST36 [bilateral], CV4, and CV6) for 20 minutes each session for 6 weeks (twice per week). The primary endpoint is the change in fatigue score from Baseline to Week 6 as measured by the Chinese version of the Brief Fatigue Inventory (BFI-C). Our secondary aim is to compare the severity of co-morbidities (e.g., depression, insomnia, and pain) among the 3 groups. DISCUSSION: The results of our trial will establish evidence for the efficacy of infrared laser moxibustion for CRF, a very common and challenging symptom. TRIAL REGISTRATION NUMBER: NCT03553355.


Assuntos
Neoplasias da Mama/complicações , Sobreviventes de Câncer/psicologia , Fadiga/terapia , Raios Infravermelhos/uso terapêutico , Moxibustão/métodos , China , Feminino , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
BMJ Open ; 9(7): e026904, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31366643

RESUMO

INTRODUCTION: Chronic neck pain is a challenging condition to treat in clinical practice and has a considerable impact on quality of life and disability. According to the theory of traditional Chinese medicine, acupoints and tender points may become sensitised when the body is in a diseased state. Stimulation of such sensitive points may lead to disease improvement and improved clinical efficacy. This study aims to evaluate the efficacy and safety of needling at sensitive acupoints in providing pain relief, improvement of cervical vertebral function and quality of life in patients with chronic neck pain. METHODS AND ANALYSIS: This multicentre, randomised controlled, explanatory and parallel clinical trial will include 716 patients with chronic neck pain. Study participants will be randomly assigned in a 1:1:1:1 ratio to four treatment groups: the highly sensitive acupoints group, low/non-sensitive acupoints group, sham acupuncture group and waiting-list control group. The primary outcome will be the change in the visual analogue scale score for neck pain from baseline to 4 weeks. Secondary outcomes will be the Northwick Park Neck Pain Questionnaire and McGill pain questionnaire, 12-item Short-Form health survey, Neck Disability Index, changes in the pressure pain threshold, range of cervical motion, Self-Rating Anxiety Scale, Self-Rating Depression Scale and adverse events before treatment, post-treatment, and at 4, 8, 12, 16 and 20 weeks post-treatment. The intention-to-treat approach will be used in the statistical analysis. Group comparisons will be undertaken using χ2 tests for categorical characteristics, and analysis of variance for continuous variables to analyse whether acupuncture in the highly sensitive acupoints group achieves better treatment outcomes than in each of the other three groups. ETHICS AND DISSEMINATION: Ethical approval of this study has been granted by the local Institutional Review Board (ID: 2017 KL-038). The outcomes of the trial will be disseminated through peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR1800016371; Pre-results.

6.
Intensive Crit Care Nurs ; 54: 7-14, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31395447

RESUMO

OBJECTIVES: To assess the impact of analgosedation on mortality and delirium in critically ill patients. RESEARCH METHODOLOGY: A systematic review and meta-analysis was conducted to identify studies through Pubmed, Cochrane Library, Embase and Web of Science published from June 2017 to July 2018. Only articles published in English were considered. The Cochrane Collaboration Risk of Bias Tool was used to evaluate the methodological quality of randomised trials, while Newcastle-Ottawa Scale (NOS) was used for cohort studies. RESULTS: Seventeen eligible studies were identified, including 2298 patients (1170 in the experimental group and 1128 in the control group). Varying analgesics and sedatives were investigated, showing a high clinical heterogeneity. Analgosedation significantly decreased the ICU mortality rate when compared to conventional analgesia and sedation [odds ratio (OR) 0.72, 95%CI 0.53-0.97; P = 0.03]. No significant difference was demonstrated in 28-day/hospital mortality rate [OR 0.91, 95%CI 0.70-1.18; P = 0.48] or in the incidence of delirium [OR 1.06, 95%CI 0.78-1.45; P = 0.70]. However, subgroup analysis of trials indicated a significant increase in the delirium rate (OR: 1.88, 95%CI 1.14-3.10, p = 0.01). CONCLUSION: The ICU mortality was decreased by implementing analgosedation, but the hospital mortality and the delirium rates were not. Because of the absence of higher quality study designs, clinical heterogeneity and inclusion of small number of studies, the analysis results must be cautiously interpreted.

7.
ACS Synth Biol ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31465214

RESUMO

As an important posttranscriptional regulatory machinery mediated by ~21nt short-interfering double-stranded RNA (siRNA), RNA interference (RNAi) is a powerful tool to delineate gene functions and develop therapeutics. However, effective RNAi-mediated silencing requires multiple siRNAs for given genes, a time-consuming process to accomplish. Here, we developed a user-friendly system for single-vector-based multiplex siRNA expression by exploiting the unique feature of restriction endonuclease BstXI. Specifically, we engineered a BstXI-based shotgun cloning (BSG) system, which consists of three entry vectors with siRNA expression units (SiEUs) flanked with distinct BstXI sites, and a retroviral destination vector for shotgun SiEU assembly. For proof-of-principle studies, we constructed multiplex siRNA vectors silencing ß-catenin and/or Smad4 and assessed their functionalities in mesenchymal stem cells (MSCs). Pooled siRNA cassettes were effectively inserted into respective entry vectors in one-step, followed shotgun seamless assembly of pooled BstXI-digested SiEU fragments into retroviral destination vector. We found these multiplex siRNAs effectively silenced ß-catenin and/or Smad4, and inhibited Wnt3A- or BMP9-specific reporters and downstream target expression in MSCs. Furthermore, multiplex silencing of ß-catenin and/or Smad4 diminished Wnt3A and/or BMP9-induced osteogenic differentiation. Collectively, the BSG system is a user-friendly technology for single-vector-based multiplex siRNA expression to study gene functions and develop experimental therapeutics.

8.
Zhongguo Zhen Jiu ; 39(8): 889-95, 2019 Aug 12.
Artigo em Chinês | MEDLINE | ID: mdl-31397138

RESUMO

The internationally-accepted Consolidated Standards for Reporting of Trials (CONSORT) and Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) were applied to evaluate the literature quality of randomized controlled trials (RCTs) regarding acupuncture for chronic neck pain in past 10 years. The literature of RCTs regarding acupuncture for chronic neck pain was searched by computer; the English literature was searched in PubMed and EMbase, while the Chinese literature was searched in CNKI, Wanfang database, VIP database and China Biomedical Literature Database. The literature published from January 2008 to January 2018 was searched. As a result, 29 Chinese articles and 10 English articles were included. According to CONSORT, among Chinese articles, 28 articles (96.6%) described baseline data, 23 articles (79.3%) described randomization, 0 articles (0.0%) described allocation concealment, 3 articles (10.3%) described blind method; among English articles, 6 articles (60.0%) described baseline data, 8 articles (80.0%) described randomization, 8 articles (80.0%) described allocation concealment, and 7 articles (70.0%) described blind method. According to STRICTA, among Chinese articles, 8 articles (27.6%) described needle instrument selection, 18 articles (62.1%) described needle depth, 24 articles (82.8%) described needling sensation, and 0 articles (0.0%) described acupuncturist' qualifications; among English articles, 5 articles (50.0%) described needle instrument selection, 8 articles (80.0%) described needle depth, 3 articles (30.0%) described needling sensation, and 4 articles (40.0%) described acupuncturist' qualifications. In conclusion, the reporting of acupuncture details in Chinese literature is superior to that in English literature, while the reporting of trial design in English literature is slightly superior to that in Chinese literature. Moreover, both Chinese and English literature need to further improve clinical trial design to improve the reporting quality of clinical evidence based on CONSORT and STRICTA.

9.
J Gen Virol ; 100(8): 1222-1233, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31259681

RESUMO

Rabies, caused by rabies virus (RABV), is a fatal zoonosis, which still poses a threat to public health in most parts of the world. Glycoprotein of RABV is the only viral surface protein, which is critical for the induction of virus-neutralizing antibodies (VNA). In order to improve the production of VNA, recombinant RABVs containing two copies of G gene and codon-optimized G gene were constructed by using reverse genetics, named LBNSE-dG and LBNSE-dOG, respectively. After being inoculated into the mouse brains, LBNSE-dOG induced more apoptosis and recruited more inflammatory cells than LBNSE-dG and LBNSE, resulting in reduced virulence in vivo. After intramuscular (im) immunization in mice, LBNSE-dOG promoted the formation of germinal centres (GCs), the recruitment of GC B cells and the generation of antibody-secreting cells (ASCs) in the draining lymph nodes (LNs). Consistently, LBNSE-dOG boosted the production of VNA and provided better protection against lethal RABV challenge than LBNSE-dG and LBNSE when it was used as both live and inactivated vaccines. Our results demonstrate that the codon-optimized RABV LBNSE-dOG displays attenuated pathogenicity and enhanced immunogenicity, therefore it could be a potential candidate for the next generation of rabies vaccines.

10.
Food Chem Toxicol ; 132: 110653, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31265866

RESUMO

Methamphetamine (MA) and ketamine (KET) are widely abused drugs individually. Previous surveys have revealed that the combined consumption of MA and KET were prevalent in illicit drugs abusers. However, few studies on the toxic effects induced by the combination of MA and KET have been reported. In this study, combined treatments were carried out using 3 × 3 full factorial design to determine the combined effects of MA and KET on apoptosis, oxidative stress and genotoxicity in HepG2 cells. Higher apoptosis and oxidative damage were observed in the MA treatments groups. Compared with control groups, the maximum apoptotic rate and level of malondialdehyde were ∼7.7 fold and ∼5.5 fold respectively. The mechanism that excessive oxidative stress resulted in cell apoptosis and DNA damage was inferred. For the joint effects, synergistic or additive interactions were found at different biological endpoints for various combinations, likely due to the mechanism in which MA promotes the metabolism of KET, which together provokes even greater oxidative stress. In conclusion, synergistic or additive interactions between MA and KET enhance cytotoxicity, oxidative damage and genotoxicity in HepG2 cells more than either of the drugs alone, which implies higher risk for abusers when exposed to the polydrug situation.

11.
ACS Nano ; 13(8): 8811-8825, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31328922

RESUMO

Cancer metastasis is a serious concern and a major reason for treatment failure. Herein, we have reported the development of an effective and safe nanotherapeutic strategy that can eradicate primary tumors, inhibit metastasizing to lung, and control the metastasis and growth of distant tumors. Briefly, ferrimagnetic vortex-domain iron oxide nanoring (FVIO)-mediated mild magnetic hyperthermia caused calreticulin (CRT) expression on the 4T1 breast cancer cells. The CRT expression transmitted an "eat-me" signal and promoted phagocytic uptake of cancer cells by the immune system to induce an efficient immunogenic cell death, further leading to the macrophage polarization. This mild thermotherapy promoted 88% increase of CD8+ cytotoxic T lymphocyte infiltration in distant tumors and triggered immunotherapy by effectively sensitizing tumors to the PD-L1 checkpoint blockade. The percentage of CD8+ cytotoxic T lymphocytes can be further increased from 55.4% to 64.5% after combining with PD-L1 blockade. Moreover, the combination treatment also inhibited the immunosuppressive response of the tumor, evidenced by significant down-regulation of myeloid-derived suppressor cells (MDSCs). Our results revealed that the FVIO-mediated mild magnetic hyperthermia can activate the host immune systems and efficiently cooperate with PD-L1 blockade to inhibit the potential metastatic spreading as well as the growth of distant tumors.

12.
J Food Biochem ; 43(4): e12812, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31353582

RESUMO

In this present study, rhinacanthins-rich extract (RRE) and rhinacanthin C (RC) the main bioactive constituent of Rhinacanthus nasutus was investigated for their protective effect against diabetic nephropathy (DN). Diabetes was induced by administering nicotinamide (100 mg/kg, i.p.)/streptozotocin (60 mg/kg, i.p.) and diabetic rats were orally administered with RRE and RC for 4 weeks. RRE and RC significantly reduced the kidney index, renal oxidative stress markers, and pro-inflammatory cytokines. Furthermore, RRE and RC increased renal levels of glutathione, superoxide dismutase, catalase, and attenuated diabetic induced renal damages. In conclusion, RRE and RC confer protective effect against DN through the inhibition of oxidative stress and inflammation and could be a potential medicinal or nutritional supplement for the prevention of DN. PRACTICAL APPLICATIONS: Rhinacanthus nasutus is a medicinal plant that is extensively used in Thai traditional medicine as an antibacterial, antifungal, antidiabetic, and anti-inflammatory agent. The plant is rich in naphthoquinones, which confer it with several excellent bioactivities. The rich extract of the leaves was prepared with three major bioactive components and the extract was evaluated for its renoprotective effect in diabetic rats. The results from this study provides valuable pharmacological information that supports the use of the plant, especially the rich extract in the prevention and treatment of diabetes and diabetic complications.

13.
JAMA Intern Med ; 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31355870

RESUMO

Importance: The effects of acupuncture as adjunctive treatment to antianginal therapies for patients with chronic stable angina are uncertain. Objective: To investigate the efficacy and safety of acupuncture as adjunctive therapy to antianginal therapies in reducing frequency of angina attacks in patients with chronic stable angina. Design, Setting, and Participants: In this 20-week randomized clinical trial conducted in outpatient and inpatient settings at 5 clinical centers in China from October 10, 2012, to September 19, 2015, 404 participants were randomly assigned to receive acupuncture on the acupoints on the disease-affected meridian (DAM), receive acupuncture on the acupoints on the nonaffected meridian (NAM), receive sham acupuncture (SA), and receive no acupuncture (wait list [WL] group). Participants were 35 to 80 years of age with chronic stable angina based on the criteria of the American College of Cardiology and the American Heart Association, with angina occurring at least twice weekly. Statistical analysis was conducted from December 1, 2015, to July 30, 2016. Interventions: All participants in the 4 groups received antianginal therapies as recommended by the guidelines. Participants in the DAM, NAM, and SA groups received acupuncture treatment 3 times weekly for 4 weeks for a total of 12 sessions. Participants in the WL group did not receive acupuncture during the 16-week study period. Main Outcomes and Measures: Participants used diaries to record angina attacks. The primary outcome was the change in frequency of angina attacks every 4 weeks from baseline to week 16. Results: A total of 398 participants (253 women and 145 men; mean [SD] age, 62.6 [9.7] years) were included in the intention-to-treat analyses. Baseline characteristics were comparable across the 4 groups. Mean changes in frequency of angina attacks differed significantly among the 4 groups at 16 weeks: a greater reduction of angina attacks was observed in the DAM group vs the NAM group (difference, 4.07; 95% CI, 2.43-5.71; P < .001), in the DAM group vs the SA group (difference, 5.18; 95% CI, 3.54-6.81; P < .001), and in the DAM group vs the WL group (difference, 5.63 attacks; 95% CI, 3.99-7.27; P < .001). Conclusions and Relevance: Compared with acupuncture on the NAM, SA, or no acupuncture (WL), acupuncture on the DAM as adjunctive treatment to antianginal therapy showed superior benefits in alleviating angina. Trial Registration: ClinicalTrials.gov identifier: NCT01686230.

14.
Arch Gynecol Obstet ; 300(3): 683-691, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31256231

RESUMO

PURPOSE: The potential therapeutic benefits of lymphadenectomy in endometrial cancer (EC) patients are still ambiguous. Therefore, a population-based retrospective analysis was conducted to determine the association between lymphadenectomy and survival in elderly female patients with stage I endometrioid EC. METHODS: The Surveillance, Epidemiology, and End Results (SEER) program database was retrospectively analyzed, and data of 63,372 female patients with early-stage type I EC from 1988 to 2013 were collected. The main patient and tumor characteristics included marital status, age, ethnicity, time of diagnosis, tumor grade, radiotherapy, and lymphadenectomy status. Kaplan-Meier and Cox proportional hazard regression analyses were performed to determine the association between lymph node dissection and the overall survival (OS) and cancer-specific survival in women older than 50 years with stage I endometrioid EC. RESULTS: The majority (83.7%) of the patients who met the inclusion criteria for the study were older than 50 years. In both grade 1 and 2 patients aged over 50 years, lymph node conservation was associated with a higher mortality risk compared to lymphadenectomy (all P < 0.005). Multivariate analysis indicated that lymphadenectomy was an independent predictor of improved OS in early-stage type 1 EC patients, with hazard ratios of 0.893 and 0.827 for the grade 1 and grade 2 patients, respectively (P < 0.0001). CONCLUSIONS: Lymphadenectomy could improve long-term OS in women older than 50 years with grade 1 and 2 endometrioid EC.

15.
Eur J Med Chem ; 180: 524-535, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31336310

RESUMO

Curcumin (CU), an edible natural pigment from Curcuma Longa, has demonstrated extensive anti-tumor effect in vivo and in vitro. With the property of reversing drug resistance and low toxicity, CU has been considered to develop a new adjuvant chemotherapy protocol of cancer. However, the poor stability, solubility, in vivo bioavailability and weak activity of CU greatly limit its clinical application. Therefore, CU analogues have been extensively studied. Starting from the study of natural CU analogues, multiple approaches are being sought to obtain more stable, soluble and effective analogues of CU. This review focuses on the progress of these approaches to more potent CU analogues.

16.
Chemosphere ; 237: 124437, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31356994

RESUMO

Fluoride is known to affect the inflammatory process and autoregulation of immune responses, but the molecular mechanism by which fluoride causes innate immune injury remain largely unknown. Also, studies on sodium fluoride (NaF)-caused alteration of TLR signaling are still lacking. In the present study, we examined the effects of NaF on the mRNA and protein expression levels of TLR2/MyD88 signaling pathway molecules in the mouse spleen by using the methods of qRT-PCR and Western blotting. Consequently, we elucidated the mechanism underlying the effects of NaF on innate immunity. Two hundred and forty ICR mice were randomly divided into 4 groups with intragastric administration of distilled water in the control group and 12, 24, 48 mg/kg of NaF treatment in the experiment groups for 42 days. The findings revealed that NaF impaired splenic innate immunity in mice via inactivation of TLR2/MyD88 signaling pathway. NaF-inactivated TLR2/MyD88 signaling pathway was identified by prominently downregulated mRNA and protein expression levels of TLR2/MyD88, IRAK4, IRAK1, TRAF6, TAK1, MKK4/MKK7 and c-Jun, which ultimately altered the expression levels of IL-1ß, IL-4, IL-6 and IL-8 to attenuate innate immunity.

17.
Anal Chem ; 91(16): 10731-10737, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31342745

RESUMO

A G-triplex, a new kind of DNA structure, has been identified as an intermediate in the folding of G-quadruplexes. However, the studies on G-triplexes are still very limited, and the functions and applications of G-triplexes need to be further developed. In this paper, a new G-triplex sequence (5'-CTGGGAGGGAGGGA-3', G3), obtained by truncating four bases (GGGA) from the 3' end of an 18-base G-quadruplex sequence (G4), was found to significantly decrease the diffusion current of methylene blue (MB). In particular, we proved that (a) MB stabilized the structure of G3 and increased the Tm of G3 considerably based on circular dichroism; and (b) MB formed a 1:1 noncovalent complex with G3 based on electrospray ionization mass spectrometry. Moreover, molecular dynamics simulations established reliable speculation in the folding topology of G3 and interaction sites between G3 and MB. Based on the strong affinity of G3 with MB, we further developed a novel function of G3 as an electrochemical signal read-out and applied it in the fabrication of a sensitive homogeneous electrochemical aptasensor for cocaine. The features we observed in the G3/MB complex will serve as a new inspiring guideline for developing functional short G-rich ligands.

18.
Virol Sin ; 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31254272

RESUMO

Rabies is a zoonotic disease that still causes 59,000 human deaths each year, and rabies vaccine is the most effective way to control the disease. Our previous studies suggested that the maturation of DC plays an important role in enhancing the immunogenicity of rabies vaccine. Flt3L has been reported to own the ability to accelerate the DC maturation, therefore, in this study, a recombinant rabies virus expressing mouse Flt3L, designated as LBNSE-Flt3L, was constructed, and its immunogenicity was characterized. It was found that LBNSE-Flt3L could enhance the maturation of DC both in vitro and in vivo, and significantly more TFH cells and Germinal Center B (GC B) cells were generated in mice immunized with LBNSE-Flt3L than those immunized with the parent virus LBNSE. Consequently, expressing of Flt3L could elevate the level of virus-neutralizing antibodies (VNA) in immunized mice which provides a better protection from a lethal rabies virus challenge. Taken together, our study extends the potential of Flt3L as a good adjuvant to develop novel rabies vaccine by enhancing the VNA production through activating the DC-TFH-GC B axis in immunized mice.

19.
Medicine (Baltimore) ; 98(24): e16027, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31192956

RESUMO

BACKGROUND: Assessing the effectiveness and safety of acupuncture therapy for treating patients with radiotherapy-induced nausea and vomiting (RINV) is the main purpose of this systematic review protocol. METHODS: The following electronic databases will be searched from inception to Sep 2019: Cochrane Central Register of Controlled Trials, PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure, Traditional Chinese Medicine, Chinese Biomedical Literature Database, Wan-Fang Database, and Chinese Scientific Journal Database. All published randomized controlled trials in English or Chinese related to acupuncture for RINV will be included. The primary outcome is the severity and frequency of RINV during radiotherapy. The secondary outcomes is the physical condition and quality of life after radiotherapy. Two reviewers will conduct the study selection, data extraction, and assessment independently. The assessment of risk of bias and data synthesis will be conducted with Review Manager Software V.5.2. RESULTS: The results will provide a high-quality synthesis of current evidence for researchers in this subject area. CONCLUSION: The conclusion of our study will provide evidence to judge whether acupuncture is an effective intervention for patients suffered from RINV. PROSPERO REGISTRATION NUMBER: CRD42019130952.


Assuntos
Terapia por Acupuntura , Náusea/etiologia , Náusea/terapia , Radioterapia/efeitos adversos , Revisão Sistemática como Assunto , Vômito/etiologia , Vômito/terapia , Humanos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Cancer Gene Ther ; 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31222181

RESUMO

MicroRNAs (miRNAs) are ~22 nucleotide noncoding RNAs that are involved in virtually all aspects of cellular process as their deregulations are associated with many pathological conditions. Mature miRNAs (mMIRs) are generated through a series of tightly-regulated nuclear and cytoplasmic processing events of the transcribed primary, precursor and mMIRs. Effective manipulations of miRNA expression enable us to gain insights into miRNA functions and to explore potential therapeutic applications. Currently, overexpression of miRNAs is achieved by using chemically-synthesized miRNA mimics, or shRNA-like stem-loop vectors to express primary or precursor miRNAs, which are limited by low transfection efficacy or rate-limiting miRNA processing. To overcome rate-limiting miRNA processing, we developed a novel strategy to express mMIRs which are driven by converging U6/H1 dual promoters. As a proof-of-concept study, we constructed mMIR expression vectors for hsa-miR-223 and hsa-Let-7a-1, and demonstrated that the expressed mMIRs effectively silenced target gene expression, specifically suppressed miRNA reporter activity, and significantly affected cell proliferation, similar to respective primary and precursor miRNAs. Furthermore, these mMIR expression vectors can be easily converted into retroviral and adenoviral vectors. Collectively, our simplified mMIR expression system should be a valuable tool to study miRNA functions and/or to deliver miRNA-based therapeutics.

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