Nonviral siRNA delivery systems for pancreatic cancer therapy.

The serious drawbacks of the conventional treatment of pancreatic ductal adenocarcinoma (PDAC) such as nonspecific toxicity and high resistance to chemo and radiation therapy, have prompted the development and application of countless small interfering RNA (siRNA)-based therapeutics. Recent advances in drug delivery systems hold great promise for improving siRNA-based therapeutics and developing a new class of drugs, known as nano-siRNA drugs. However, many fundamental questions, regarding toxicity, immunostimulation, and poor knowledge of nano-bio interactions, need to be addressed before clinical translation. In this review, we provide recent achievements in the design and development of various nonviral delivery vehicles for pancreatic cancer therapy. More importantly, codelivery of conventional anticancer drugs with siRNA as a new revolutionary pancreatic cancer combinational therapy is completely discussed.

Overcoming the blood-brain barrier in neurodegenerative disorders and brain tumours.

Drug delivery is one of the major challenges in the treatment of central nervous system disorders. The brain needs to be protected from harmful agents, which are done by the capillary network, the so-called blood-brain barrier (BBB). This protective guard also prevents the delivery of therapeutic agents to the brain and limits the effectiveness of treatment. For this reason, various strategies have been explored by scientists for overcoming the BBB from disruption of the BBB to targeted delivery of nanoparticles (NPs) and cells and immunotherapy. In this review, different promising brain drug delivery strategies including disruption of tight junctions in the BBB, enhanced transcellular transport by peptide-based delivery, local delivery strategies, NP delivery, and cell-based delivery have been fully discussed.

Antimicrobial peptides: a promising strategy for lung cancer drug discovery?

INTRODUCTION: Antimicrobial peptides (AMPs), also called host defense peptides (HDPs), are identified in almost any form of life, which play an important role in innate immune systems. They have a broad spectrum of antifungal, antiviral, antibacterial, and anticancer activities. Lung cancer remains the leading cause of global cancer-related death. Unfortunately, lung cancer chemotherapy is accompanied by serious side effects, nonspecific toxicity, and multidrug resistance. Hence, to overcome these drawbacks, anticancer peptides (ACPs) derived from AMPs may represent a potential promising synergistic treatment strategy for lung cancer. AREAS COVERED: In this review, the authors provide the recent advancements in the use of AMPs for the treatment of lung cancer. Furthermore, the anti-lung cancer modes of action of these peptides have been fully reviewed. Importantly, various strategies for increasing the efficiency and safety of AMPs have been discussed. EXPERT OPINION: The combination of AMPs and other cancer treatment approaches such as chemotherapy, nanoparticle-based delivery systems, and photodynamic therapy can be used as a promising revolutionary strategy for the treatment of lung cancer. The most significant limitations of this strategy that need to be focused on are low efficiency and off-target events.

The effect of berberine supplementation on obesity indices: A dose- response meta-analysis and systematic review of randomized controlled trials.

BACKGROUND: and purpose: Clinical studies investigating the effects of berberine supplementation on anthropometric indices in humans have generated inconsistent results. Thus, the objective of this systematic review and meta-analysis was to clarify the effects of berberine supplementation on obesity indices in human subjects. METHODS: Several online medical databases were systematically searched up to February 2019. All clinical trials exploring the effects of berberine supplementation on indices of obesity were included. The combined weighted mean difference (WMD) of eligible studies was assessed using a random-effects model. We evaluated publication bias by using the Egger's test. RESULTS: Overall, 10 studies were included. The combined outcomes suggested a significant influence of berberine administration on body mass index (BMI) (WMD: -0.29 kg/m2, 95% CI: -0.51 to -0.08, p = 0.006) and waist circumference (WC) (WMD: -2.75 cm, 95% CI: -4.88 to -0.62, p = 0.01). However, berberine supplementation yielded no significant decline in body weight (BW) (WMD: -0.11 kg, 95% CI: -0.99 to 0.76, p = 0.79). Following the dose-response evaluation, berberine intake was found to significantly reduce BMI (r = -0.02) and WC (r = -0.72) based on treatment duration. CONCLUSION: The results of the current study support the use of berberine supplementation for the improvement of obesity indices.

Delivery of genome editing tools: A promising strategy for HPV-related cervical malignancy therapy.

INTRODUCTION: Persistent high-risk human papillomavirus infection is the main cause of various types of cancer especially cervical cancer. The E6 and E7 oncoproteins of HPV play critical roles in promoting carcinogenesis and cancer cell growth. As a result, E6 and E7 oncogenes are considered as promising therapeutic targets for cervical cancer. Recently, the development of genome-editing technologies including transcription activator-like effector nucleases (TALEN), meganucleases (MNs), zinc finger nucleases (ZFN), and more importantly clustered regularly interspaced short palindromic repeat-CRISPR-associated protein (CRISPR-Cas) has sparked a revolution in the cervical cancer-targeted therapy. However, due to immunogenicity, off-target effect, renal clearance, guide RNA (gRNA) nuclease degradation, and difficult direct transportation into the cytoplasm and nucleus, the safe and effective delivery is considered as the Achilles' heel of this robust strategy. AREAS COVERED: In this review, we discuss cutting-edge available strategies for in vivo delivery of genome-editing technologies for HPV-induced cervical cancer therapy. Moreover, the combination of genome-editing tools and other therapies has been fully discussed. EXPERT OPINION: The combination of nanoparticle-based delivery systems and genome-editing tools is a promising powerful strategy for cervical cancer therapy. The most significant limitations of this strategy that need to be focused on are low efficiency and off-target events.

The influence of metformin on IGF-1 levels in humans: A systematic review and meta-analysis.

BACKGROUND: A meta-analysis is needed to comprehensively consolidate findings from the influence of metformin on IGF-1 levels. The present study was conducted with the objective to accurately evaluate the influence of metformin intake on IGF-1 levels via a meta-analysis of randomized controlled trials. METHODS: A comprehensive systematic search was carried out in PubMed/MEDLINE, Web of Science, SCOPUS and Embase from inception until June 2019. Weighted mean difference (WMD) with the 95 % CI were applied for estimating the effects of metformin on serum IGF-1 levels. RESULTS: 11 studies involving a total of 569 individuals reported changes in IGF-1 plasma concentrations as an outcome measure. Pooled results demonstrated an overall non-significant decline in IGF-1 following metformin intake (WMD: -8.292 ng/ml, 95 % CI: -20.248, 3.664, p = 0.174) with heterogeneity among (p = 0.000,I2 = 87.1 %). The subgroup analyses displayed that intervention duration <12 weeks on children (WMD:-55.402 ng/ml, 95 % CI: -79.845, -30.960, I2 = 0.0 %) significantly reduced IGF-1. Moreover, in age 18 < years older metformin intake (WMD: 15.125 ng/ml, 95 % CI: 5.522, 24.729, I2 = 92.5 %) significantly increased IGF-1 than 18 ≤ years older (WMD:-1.038 ng/ml, 95 % CI: -3.578,1.502,I2 = 78.0 %). Following dose-response evaluation, metformin intake reduced IGF-1 (coefficient for dose-response analysis= -13.14, P = 0.041 and coefficient for liner analysis= -0.066, P = 0.038) significantly based on treatment duration. CONCLUSION: We found in children, intervention duration <12 weeks yielded significant reductions in IGF-1, whilst paradoxically, in participants >18 years old, metformin intake significantly increased IGF-1. We suggest that caution be taken when interpreting the findings of this review, particularly given the discordant supplementation practices between children and adults.

Impact of phytosterol supplementation on plasma lipoprotein(a) and free fatty acid (FFA) concentrations: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Although some earlier studies have indicated the effect of phytosterol (PS) supplementation on serum lipoprotein(a) (Lp(a)) and free fatty acid (FFA) concentration, findings are still conflicting. We aimed to assess the impact of PS supplementation on serum Lp(a) and FFA concentration through a systematic review and meta-analysis of available RCTs. METHODS AND RESULTS: We performed a systematic search of all available RCTs conducted up to 21 February 2019 in the following databases: PubMed, Scopus, and Cochrane. The choice of fixed- or random-effect model for analysis was determined according to the I2 statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Pooling of 12 effect sizes from seven articles revealed a significant reduction of Lp(a) levels following PS supplementation (MD: -0.025 mg/dl, 95% CI: -0.045, -0.004, p = 0.017) without significant heterogeneity among the studies (I2 = 0.0%, p = 0.599). Also, PS supplementation significantly lowered FFA (MD: -0.138 mg/dl, 95% CI: -0.195, -0.081, p = 0.000) without significant heterogeneity among the studies (I2 = 0.0%, p = 0.911). The results for meta-regression and sensitivity analysis were not significant. CONCLUSION: The meta-analysis suggests that oral PS supplementation could cause a significant reduction in serum Lp(a) and FFA.

The effect of green coffee extract supplementation on blood pressure: A systematic review and meta-analysis of randomized controlled trials.

Given the proliferation in studies investigating green coffee bean extract (GCBE) supplementation, the purpose of this study was to determine the efficacy and effectiveness of GCBE supplementation on indices of blood pressure. The literature search was performed in four databases, namely, PubMed/Medline, Scopus, the Cochrane Library, and Google Scholar, to identify clinical trials that examined the effects of green coffee supplements on systolic blood pressure (SBP) and diastolic blood pressure (DBP) up to February 2019. Mean change and standard deviation (SD) of the outcome measures were used to estimate the mean difference between the intervention group and the control group at follow-up. Nine studies reported SBP and DBP as an outcome measure. Results revealed significant reduction in SBP (weighted mean difference: -3.093 mmHg, 95% confidence interval [CI]: -3.914, -2.273; I2 = 0.0%) and DBP (-2.170 mmHg, 95% CI: -2.749, -1.590; I2 = 46.5%) after green coffee supplementation with low heterogeneity among the studies. In addition, in subgroup analysis, a significant reduction in SBP and DBP in studies with hypertensive patients, green coffee dosage <400 mg, and administered for 4 weeks was identified. The results of the current meta-analysis study support the use of GCBE supplementation for the improvement of blood pressure indices, with subgroup analysis highlighting improvements in hypertensive patients.

The effect of green-coffee extract supplementation on obesity: A systematic review and dose-response meta-analysis of randomized controlled trials.

BACKGROUND: Given that the most recent systematic review investigating Green-Coffee Extract (GCE) as a weight loss facilitator was nearly a decade ago and that the authors reported there no consensus on the effect of GCE/CGA (Chlorogenic acids) on body composition indices, a comprehensive systematic review and dose-response meta-analysis of all available randomized controlled trial (RCTs) was undertaken to examine the effect of GCE and CGA intervention on body weight (BW), body mass index (BMI) and waist circumference (WC) in adults. METHODS: We conducted a systematic search of all available randomized controlled trials (RCTs) performed up to June 2019 in the following electronic databases: PubMed, Scopus and Google Scholar. RCTs that investigated the effect GCE/CGA Supplementation on BW, BMI and WC in adults were included for final analysis. The pooled weight mean difference (WMD) of included studies was estimated using a random-effects model. RESULTS: A total of 13 articles with 16 RCTs were included in the meta-analysis. Results revealed significant reduction in BMI (WMD: -0.403 kg/m2, 95% CI: -0.800, -0.005, p = 0.047) and no significant change in BW (WMD: -0.585 kg, 95% CI: -1.498, 0.329, p = 0.210) and WC (WMD: -0.847 cm, 95% CI: -1.764, 0.071, p = 0.070). In the subgroup analysis, studies that were conducted on baseline BMI ≥25 kg/m2 revealed a significant greater reduction in body weight and BMI than those performed on baseline BMI <25 kg/m2. Moreover, short supplementation periods of less than 4 weeks had no effect. CONCLUSION: The results of current meta-analysis study support the use of GCE supplementation for the improvement of obesity indices, with sub-group analysis highlighting greater improvements in individuals with a starting BMI ≥25 kg/m2.