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Glioblastoma multiforme (GBM) is the most lethal brain malignancy which involves multi-gene abnormality. Unfortunately, effective therapy against GBM remains lacking. Previously, we found that NRP-1 and its downstream NRP-1/GIPC1 pathway played an important role in GBM. In our study, we further investigated the upstream signaling of NRP-1 to understand how it is regulated. First, we identified that hsa-miR-124-3p was miRNA differentially expressed in GBM and in normal brain tissues by high-throughput sequencing. Then, by dual luciferase reporter gene, we found miR-124-3p can specially bind to the 3'UTR region of the NRP-1 thus suppresses its expression. Moreover, miR-124-3p overexpression significantly inhibited GBM cell proliferation, migration and tumor angiogenesis which resulted in GBM apoptosis and cell cycle arrest, putatively via NRP-1 mediated PI3K/Akt/NFκB pathways activation in GBM cells. Meanwhile, miR-124-3p overexpression also suppressed tumor growth and reduced tumor angiogenesis when targeted by NRP-1 in a PDX model. Furthermore, NRP-1 mAb exerted synergistic inhibitory effects with miR-124-3p overexpression in GBM. Thus, we discovered that miR-124-3p acts as the upstream suppressor of NRP-1 which promotes GBM cell development and growth by PI3K/Akt/NFκB pathway. The miR-124-3p/NRP-1/GIPC1 pathway as a new pathway has a vital role in GBM, and it could be considered as the potential target for malignant gliomas in future.

BackgroundAccording to the National Health survey only 3% of the population has controlled hypertension. This study was designed to elucidate the knowledge about hypertension in hypertensive patients at three tertiary care centers in Karachi. Secondly we sought to compare the knowledge of those with uncontrolled hypertension and controlled hypertension.MethodsIt was a cross-sectional study conducted at The Aga Khan University hospital (AKUH), Ziauddin Hospital (ZH) and Civil hospital, Karachi (CHK. All diagnosed Hypertensive patients (both inpatients and outpatients) coming to a tertiary care hospital in Pakistan aged > 18 years were included. Patients were categorized into 2 groups: controlled and uncontrolled hypertension based on their initial BP readings on presentation Uncontrolled Hypertension was defined as average BP ≥ 140/90 mm Hg in patients on treatment. Controlled Hypertension (HTN) was defined as average BP <140/90 mm Hg in patients on treatment. Standardized methods were used to record BP in the sitting position. Knowledge was recorded as a15 item question. Primary outcome was knowledge about hypertension.ResultsA total of 650 participants were approached and consented 447 were found eligible. 284(63.5%) were from Aga Khan University, 101(22.6) from Dow University of health sciences and 62(13.9) were from Ziauddin University. Mean (SD) age of participants was 57.7(12) years, 50.1(224) were men. Controlled hypertension was present in 323(72.3) and uncontrolled hypertension was present in 124(27.4). The total mean (SD) Knowledge score was 20.97(4.93) out of a maximum score of 38. On comparison of questions related to knowledge between uncontrolled and controlled hypertension, there was statistically significant different in; meaning of hypertension (p <0.001), target SBP(p0.001), target DBP(p 0.001), importance of SBP versus DBP, improvement of health with lowering of blood pressure (p 0.002), high blood pressure being asymptomatic (p <0.001), changing lifestyle improves blood pressure(p 0.003),hypertension being a lifelong disease (<0.001), lifelong treatment with antihypertensives(<0.001) and high blood pressure being part of aging(<0.001). On comparison of knowledge as a composite score between uncontrolled and controlled hypertensive; Mean (SD) score was 21.85(4.74) v18.67 (4.70) (p value: < 0.001). On multivariate analysis; gender β (95% CI) 1.67(0.75, 2.59) p <0.001, uncontrolled blood pressure; -2.70(−3.76,-1.67) p <0.001, Sindhi ethnicity; -1.79(−3.25,-3.27) p 0.01 and pukhtoon ethnicity; -2.72(−4.13,-1.32) p <0.001 were significantly associated with knowledge score.ConclusionKnowledge about hypertension in hypertensive patients is not adequate and is alarmingly poor in patients with uncontrolled hypertension. More emphasis needs to be made on target blood pressure and need for taking antihypertensives for life to patients by physicians.

The proposed MCI is feasible for implementation and requires long-term, large-scale evaluation in the rural public health infrastructure in South Asian countries to determine sustainability of health system changes and BP control. If these long-term effects are confirmed, MCI may be a long-term strategy for tackling rising rates of cardiovascular disease in low-resourced countries.Clintrial.gov NCT02341651.

Objective. Systematic review and meta-analysis to observe the efficacy and safety of stem cell transplantation therapy in patients with brain ischemia. Methods. We searched Cochrane Library, PubMed, Ovid, CBM, CNKI, WanFang, and VIP Data from its inception to December 2015, to collect randomized controlled trials (RCT) of stem cell transplantation for the ischemic stroke. Two authors independently screened the literature according to the inclusion and exclusion criteria, extracted data, and assessed the risk of bias. Thereafter, meta-analysis was performed. Results. Sixteen studies and eighteen independent treatments were included in the current meta-analysis. The results based upon the pooled mean difference from baseline to follow-up points showed that the stem cell transplantation group was superior to the control group with statistical significance in the neurologic deficits score (NIHSS, MD = 1.57; 95% CI, 0.64–2.51; I 2 = 57%; p = 0.001), motor function (FMA, MD = 4.23; 95% CI, 3.08–5.38; I 2 = 0%; p < 0.00001), daily life ability (Barthel, MD = 8.37; 95% CI, 4.83–11.91; I 2 = 63%; p < 0.00001), and functional independence (FIM, MD = 8.89; 95% CI, 4.70–13.08; I 2 = 79%; p < 0.0001). Conclusions. It is suggested that the stem cell transplantation therapy for patients with brain ischemic stroke can significantly improve the neurological deficits and daily life quality, with no serious adverse events. However, higher quality and larger data studies are required for further investigation to support clinical application of stem cell transplantation.

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BACKGROUND The setting of a randomized trial can determine whether its findings are generalizable and can therefore apply to different settings. The contribution of low- and middle-income countries (LMICs) to neurosurgical randomized trials has not been systematically described before. OBJECTIVE To perform a systematic analysis of design characteristics and methodology, funding source, and interventions studied between trials led by and/or conducted in high-income countries (HICs) vs LMICs. METHODS From January 2003 to July 2016, English-language trials with &gt;5 patients assessing any one neurosurgical procedure against another procedure, nonsurgical treatment, or no treatment were retrieved from MEDLINE, Scopus, and Cochrane Library. Income classification for each country was assessed using the World Bank Atlas method. RESULTS A total of 73.3% of the 397 studies that met inclusion criteria were led by HICs, whereas 26.7% were led by LMICs. Of the 106 LMIC-led studies, 71 were led by China. If China is excluded, only 8.8% were led by LMICs. HIC-led trials enrolled a median of 92 patients vs a median of 65 patients in LMIC-led trials. HIC-led trials enrolled from 7.6 sites vs 1.8 sites in LMIC-led studies. Over half of LMIC-led trials were institutionally funded (54.7%). The majority of both HIC- and LMIC-led trials evaluated spinal neurosurgery, 68% and 71.7%, respectively. CONCLUSION We have established that there is a substantial disparity between HICs and LMICs in the number of published neurosurgical trials. A concerted effort to invest in research capacity building in LMICs is an essential step towards ensuring context- and resource-specific high-quality evidence is generated.

BackgroundHigh blood pressure (BP) is the leading attributable risk for cardiovascular disease (CVD). In rural South Asia, hypertension continues to be a significant public health issue with sub-optimal BP control rates. The goal of the trial is to compare a multicomponent intervention (MCI) to usual care to evaluate the effectiveness and cost-effectiveness of the MCI for lowering BP among adults with hypertension in rural communities in Bangladesh, Pakistan and Sri Lanka.Methods/designThis study is a stratified, cluster randomized controlled trial with a qualitative component for evaluation of processes and stakeholder feedback. The MCI has five components: (1) home health education by government community health workers (CHWs), (2) BP monitoring and stepped-up referral to a trained general practitioner using a checklist, (3) training public and private providers in management of hypertension and using a checklist, (4) designating hypertension triage counter and hypertension care coordinators in government clinics and (5) a financing model to compensate for additional health services and provide subsidies to low income individuals with poorly controlled hypertension. Usual care will comprise existing services in the community without any additional training.The trial will be conducted on 2550 individuals aged ≥40 years with hypertension (with systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg, based on the mean of the last two of three measurements from two separate days, or on antihypertensive therapy) in 30 rural communities in Bangladesh, Pakistan and Sri Lanka. The primary outcome is change in systolic BP from baseline to follow-up at 24 months post-randomization. The incremental cost of MCI per CVD disability-adjusted life years averted will be computed.Stakeholders including policy makers, provincial- and district-level coordinators of relevant programmes, physicians, CHWs, key community leaders, hypertensive individuals and family members in the identified clusters will be interviewed.DiscussionThe study will provide evidence of the effectiveness and cost-effectiveness of MCI strategies for BP control compared to usual care in the rural public health infrastructure in South Asian countries. If shown to be successful, MCI may be a long-term sustainable strategy for tackling the rising rates of CVD in low resourced countries.Trial registrationClinicalTrials.gov, NCT02657746. Registered on 14 January 2016.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2018-0) contains supplementary material, which is available to authorized users.