الملخص
Polo-like kinase (PLK1) has been identified as a potential target for cancer treatment. Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain (PBD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethyl-benzofuran-2-carboxylic acid ethyl ester (designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1 PBD was confirmed using fluorescence polarization and microscale thermophoresis. This compound exerted specificity towards PLK1 over PLK2 and PLK3. MCC1019 showed cytotoxic activity in a panel of different cancer cell lines. Mechanistic investigations in A549 lung adenocarcinoma cells revealed that MCC1019 induced cell growth inhibition through inactivation of AKT signaling pathway, it also induced prolonged mitotic arrest-a phenomenon known as mitotic catastrophe, which is followed by immediate cell death apoptosis and necroptosis. MCC1019 significantly inhibited tumor growth in a murine lung cancer model without affecting body weight or vital organ size, and reduced the growth of metastatic lesions in the lung. We propose MCC1019 as promising anti-cancer drug candidate.
الملخص
OBJECTIVE@#To identify and synthesize the most recent available evidence of effectiveness of acupuncture on pain, physical function and health-related quality of life (HRQoL) in patients with rheumatoid arthritis (RA).@*METHODS@#A comprehensive search of 12 Western and Chinese databases was undertaken from their inception up to end of 2016. Randomized controlled trials (RCTs), concerning patients with RA treated with needle acupuncture, written in English, Portuguese, German or Chinese were included. Primary outcomes included pain, physical function and HRQoL. Secondary outcomes included morning stiffness, functional impairment, number of tender and swollen joints and serum concentrations of inflamatory markers. Methodological quality was assessed by three independent reviewers using the standardized critical appraisal instrument from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument.@*RESULTS@#Twenty-two studies met the inclusion criteria. Of those, 9 studies were excluded after assessment of their methodological quality. The remaining 13 original RCTs included 974 patients. Ten of these studies published in China, showed favorable statistical significant effects of acupuncture in relieving symptoms of RA compared with controls.@*CONCLUSIONS@#Evidence suggests that acupuncture interventions may have a positive effect in pain relief, physical function and HRQoL in RA patients. However, due to the heterogeneity and methodologic limitations of the studies included in this systematic review, evidence is not strong enough to produce a best practice guideline.
الملخص
<p><b>BACKGROUND</b>Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by functional disability and pain. Although acupuncture is widely used, until now Western acupuncture studies on RA have not shown conclusive positive results. Acupuncture is regarded as a reflex therapy that has effects on the human autonomic nervous system. By establishing a traditional Chinese medicine (TCM) diagnosis first, the practitioner is able to choose acupoints according to the state of each individual patient.</p><p><b>METHODS/DESIGN</b>We are interested if acupuncture, using a classical diagnostic procedure to allocate acupoints to the patient according to the Shang Han Lun theory, can be effective in relieving pain, improving hand function and increasing health-related quality of life in RA.The authors intend to harmonize TCM diagnosis according to clinical and genetic profiles. Patients with the TCM diagnosis of a so-called Turning Point syndrome will be followed up in a randomized, prospective, double-blind, placebo-controlled, multicenter and three-armed parallel-group study with a standardized treatment in order to optimize potential therapeutic effects of acupuncture on pain, strength and muscle function of patients with RA as well as the influence on inflammation and quality of life.</p><p><b>DISCUSSION</b>The findings of this study will provide important clinical information about the feasibility and efficacy of acupuncture treatment for RA patients. In addition, it will explore the feasibility of further acupuncture research.</p><p><b>TRIAL REGISTRATION NUMBER</b>ClinicalTrials.gov Identifier NCT02553005.</p>
الموضوعات
Humans , Acupuncture Therapy , Arthritis, Rheumatoid , Psychology , Therapeutics , Clinical Protocols , Double-Blind Method , Hand , Medicine, Chinese Traditional , Pilot Projects , Quality of Lifeالملخص
<p><b>BACKGROUND</b>Musicians are frequently affected by playing-related musculoskeletal disorders (PRMD). Common solutions used by Western medicine to treat musculoskeletal pain include rehabilitation programs and drugs, but their results are sometimes disappointing.</p><p><b>OBJECTIVE</b>To study the effects of self-administered exercises based on Tuina techniques on the pain intensity caused by PRMD of professional orchestra musicians, using numeric visual scale (NVS).</p><p><b>DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS</b>We performed a prospective, controlled, single-blinded, randomized study with musicians suffering from PRMD. Participating musicians were randomly distributed into the experimental (n=39) and the control (n=30) groups. After an individual diagnostic assessment, specific Tuina self-administered exercises were developed and taught to the participants. Musicians were instructed to repeat the exercises every day for 3 weeks.</p><p><b>MAIN OUTCOME MEASURES</b>Pain intensity was measured by NVS before the intervention and after 1, 3, 5, 10, 15 and 20 d of treatment. The procedure was the same for the control group, however the Tuina exercises were executed in points away from the commonly-used acupuncture points.</p><p><b>RESULTS</b>In the treatment group, but not the control group, pain intensity was significantly reduced on days 1, 3, 5, 10, 15 and 20.</p><p><b>CONCLUSION</b>The results obtained are consistent with the hypothesis that self-administered exercises based on Tuina techniques could help professional musicians controlling the pain caused by PRMD. Although our results are very promising, further studies are needed employing a larger sample size and double blinding designs.</p>
الموضوعات
Adult , Female , Humans , Male , Middle Aged , Exercise Therapy , Medicine, Chinese Traditional , Musculoskeletal Diseases , Therapeutics , Music , Prospective Studies , Self Administration , Single-Blind Methodالملخص
<p><b>BACKGROUND</b>Musicians are a prone group to suffer from working-related musculoskeletal disorder (WRMD). Conventional solutions to control musculoskeletal pain include pharmacological treatment and rehabilitation programs but their efficiency is sometimes disappointing.</p><p><b>OBJECTIVE</b>The aim of this research is to study the immediate effects of Tuina techniques on WRMD of professional orchestra musicians from the north of Portugal.</p><p><b>DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS</b>We performed a prospective, controlled, single-blinded, randomized study. Professional orchestra musicians with a diagnosis of WRMD were randomly distributed into the experimental group (n=39) and the control group (n=30). During an individual interview, Chinese diagnosis took place and treatment points were chosen. Real acupoints were treated by Tuina techniques into the experimental group and non-specific skin points were treated into the control group. Pain was measured by verbal numerical scale before and immediately after intervention.</p><p><b>RESULTS</b>After one treatment session, pain was reduced in 91.8% of the cases for the experimental group and 7.9% for the control group.</p><p><b>CONCLUSION</b>Although results showed that Tuina techniques are effectively reducing WRMD in professional orchestra musicians of the north of Portugal, further investigations with stronger measurements, double-blinding designs and bigger simple sizes are needed.</p>