Clinical effectiveness of krill oil supplementation on cardiovascular health in humans: An updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The potential role of krill oil (KO) supplementation on cardiovascular health are inconsistent in several clinical trials. Therefore, our present meta-analysis aimed to systematically evaluate the impacts of supplementation of KO on cardiovascular disease risk factors (CVDRFs). METHODS: Intervention trials assessing KO supplementation on cardiovascular disease (CVD) outcomes were systematically retrieved for pooling. The primary outcome was lipid profile. Secondary outcomes were consisted by blood pressure, glycemic indices, body composition together with inflammatory markers. We synthesized the effect sizes with 95% confidence intervals and weighted mean difference. To explore the heterogeneity source, we employed meta-regression and subgroup analysis. Quality assessment, publication bias, sensitivity-analysis and the certainty of evidence were also carried out. RESULTS: We included 14 trials (18 treatment arms) with 1458 participants. KO supplementation had beneficial effects on total cholesterol (P = 0.01), low-density lipoprotein cholesterol (P = 0.006), and triglycerides (P = 0.0005). However, no effects were found for other CVDRFs, such as blood pressure, glycemic control, body composition as well as inflammatory markers. Subgroup analyses indicated that these notably favorable effects were observed in trials with a parallel design, treatment duration <8 weeks and subjects with baseline body mass index <28 kg/m2. The above findings remained consistent in the sensitivity analysis, without obvious publication bias detected. CONCLUSIONS: The current evidence demonstrated that daily KO supplementation may as a candidate for lipid management strategies. In future, studies should pay attention to the relationships of KO intake with the incidence of CVD events or all-cause mortality.

MicroRNA-194-3p impacts autophagy and represses rotavirus replication via targeting silent information regulator 1.

BACKGROUND: Rotavirus (RV) is the main cause of serious diarrhea in infants and young children worldwide. Numerous studies have demonstrated that RV use host cell mechanisms to motivate their own stabilization and multiplication by degrading, enhancing, or hijacking microRNAs (miRNAs). Therefore, exploring the molecular mechanisms by which miRNAs motivate or restrain RV replication by controlling different biological processes, including autophagy, will help to better understand the pathogenesis of RV development. This study mainly explored the effect of miR-194-3p on autophagy after RV infection and its underlying mechanism of the regulation of RV replication. METHODS: Caco-2 cells were infected with RV and used to measure the expression levels of miR-194-3p and silent information regulator 1 (SIRT1). After transfection with plasmids and RV infection, viral structural proteins, RV titer, cell viability, and autophagy-linked proteins were tested. The degree of acetylation of p53 was further investigated. A RV-infected neonatal mouse model was constructed in vivo and was evaluated for diarrhea symptoms and lipid droplet formation. RESULTS: The results showed that miR-194-3p was reduced but SIRT1 was elevated after RV infection. Elevation of miR-194-3p or repression of SIRT1 inhibited RV replication through the regulation of autophagy. The overexpression of SIRT1 reversed the effects of miR-194-3p on RV replication. The upregulation of miR-194-3p or the downregulation of SIRT1 repressed RV replication in vivo. MiR-194-3p targeted SIRT1 to decrease p53 acetylation. CONCLUSION: These results were used to determine the mechanism of miR-194-3p in RV replication, and identified a novel therapeutic small RNA molecule that can be used against RV.

Arctigenin hinders the invasion and metastasis of cervical cancer cells via the FAK/paxillin pathway.

Context: Cervical cancer is the most common gynecological pernicious tumor with high morbidity and mortality worldwide, especially in developing countries. Arctigenin (ARG), a nature-derived component, has exhibited anti-tumor activity in various tumors. Objective: To explore the effect of ARG on cervical cancer. Materials and methods: The effect and mechanism of ARG on cervical cancer cells were explored by cell counting kit-8 (CCK-8), flow cytometry, transwell and Western blot assays. Additionally, in vivo experiment was conducted in xenografted mice by immunohistochemistry (IHC), terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) and Western blot assays. Results: ARG treatment induced both concentration-dependent and time-dependent reductions in the cell viability of SiHa and HeLa cells with a IC50 value of 9.34 µM and 14.45 µM, respectively. ARG increased the apoptosis rate and the protein levels of cleaved-caspase 3 and E-cadherin, but decreased the invaded cell numbers and the protein levels of Vimentin and N-cadherin in vitro. Mechanically, ARG inhibited the expression of focal adhesion kinase (FAK)/paxillin pathway, which was confirmed by the overexpression of FAK in SiHa cells. The inhibitory role of overexpression of FAK in proliferation and invasion, as well as its promoted role in apoptosis were reversed with ARG treatment. Meanwhile, ARG suppressed growth and metastasis, and enhanced apoptosis in vivo. Consistently, ARG administration reduced the relative protein level of p-FAK/FAK and p-paxillin/paxillin in tumor tissues of xenografted mice. Conclusion: ARG inhibited proliferation, invasion and metastasis, but enhanced apoptosis of cervical cancer via the FAK/paxillin axis.

Deoxyshikonin inhibited rotavirus replication by regulating autophagy and oxidative stress through SIRT1/FoxO1/Rab7 axis.

BACKGROUND: Rotavirus (RV) is a double-stranded RNA virus. RV prevention and treatment remain a major public health problem due to the lack of clinically specific drugs. Deoxyshikonin is a natural compound isolated from the root of Lithospermum erythrorhizon and one of the shikonin derivatives which owns remarkable therapeutic effects on multiple diseases. The purpose of this research was to inquire Deoxyshikonin's role and mechanism in RV infection. METHODS: Deoxyshikonin's function in RV was estimated using Cell Counting Kit-8 analysis, cytopathic effect inhibition assay, virus titer determination, quantitative real-time PCR, enzyme linked-immunosorbent assay, Western blot, immunofluorescence, and glutathione levels detection. Also, Deoxyshikonin's mechanism in RV was appraised with Western blot, virus titer determination, and glutathione levels detection. Moreover, Deoxyshikonin's function in RV in vivo was determined using animal models, and diarrhea score analysis. RESULTS: Deoxyshikonin owned anti-RV activity and repressed RV replication in Caco-2 cells. Furthermore, Deoxyshikonin reduced autophagy and oxidative stress caused by RV. Mechanistically, Deoxyshikonin induced low protein levels of SIRT1, ac-Foxo1, Rab7, VP6, low levels of RV titers, low autophagy and oxidative stress. SIRT1 overexpression abolished the effects of Deoxyshikonin on RV-treated Caco-2 cells. Meanwhile, in vivo research affirmed that Deoxyshikonin also possessed anti-RV function, and this was reflected in increased survival rate, body weight, GSH levels, and decreased diarrhea score, RV virus antigen, LC-3II/LC3-I. CONCLUSION: Deoxyshikonin reduced RV replication through mediating autophagy and oxidative stress via SIRT1/FoxO1/Rab7 pathway.

Calcium-sensing receptor acts as an antiviral factor for rotavirus infections and participates in cellular antiviral response.

Objectives: Rotavirus (RV) is one of the most significant pathogens associated with childhood diarrhoeal deaths worldwide. Elevated cytoplasmic calcium is required for RV replication, but the underlying mechanisms responsible for calcium influx remain poorly understood. The Calcium-sensing receptor (CaSR) is an important Ca2+ sensor that regulates the transport of Ca2+ into or out of the extracellular space by affecting the status of Ca2+ ion channels on the membrane of cells. Currently, the function of CaSR in RV replication is unclear. Materials and Methods: We evaluated the mRNA and protein levels of CaSR in RV-infected cells using qRT-PCR and Western blotting, respectively. Furthermore, we silenced or overexpressed CaSR in Caco-2 cells using siRNA or a CaSR gene contained adenovirus (Adv-CaSR). qRT-PCR, plaque assay, and Western blotting were used to determine the synthesis of virus genomic RNA, production of progeny virion, and the levels of viral proteins. The content of Ca2+ in cells was observed under confocal microscopy. Results: Compared with control cells, the RV-infected cells presented significantly decreased CaSR expression. Moreover, adenoviral-mediated over-expression or induction of CaSR by R568 greatly inhibited the RV RNA synthesis, protein expression, and formation of viroplasm plaques, thereby suppressing RV replication. In contrast, CaSR-silenced cells exhibited significantly enhanced RV replication. Compared with the Adv-Control group, the concentration of cytosolic Ca2+ significantly decreased in the Adv-CaSR group. Conclusion: These findings demonstrated that CaSR is a potential target for inhibition of RV replication. Therefore, enhancing the expression of CaSR might protect hosts from RV infections.

Clinical evidence of dietary supplementation with sesame on cardiovascular risk factors: An updated meta-analysis of randomized controlled trials.

The present analysis was to summarize the evidence of the effects of sesame and its derivatives supplementation on cardiovascular disease (CVD) risk factors by performing a meta-analysis of randomized controlled trials (RCTs). Electronic databases were searched from their inception to July 2020. Two investigators independently assessed articles for inclusion, extracted data, and statistical analysis. The quality of included articles was assessed according to the Cochrane risk of bias tool. Major outcomes were synthesized using a random effect model and presented as weighted mean difference and 95% confidence interval. Heterogeneity, subgroup analyses, sensitivity analysis, meta-regression, and publication bias were also conducted. The GRADE approach was used to evaluate the quality of evidence. Overall, 16 trials involving 908 participants were included for statistical pooling. Compared with the control group, sesame intake significantly decreased the levels of total cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure, body weight, body mass index, hip circumference, and waist circumference (P < 0.05). These results were stable in sensitivity analysis, and no significant publication bias was detected. Our findings provided evidence that sesame consumption may reduce the risk of CVD by improving blood lipids, blood pressure, and body weight management. Further large-scale, well-designed RCTs are required to confirm these results.

circRNA_0006470 promotes the proliferation and migration of gastric cancer cells by functioning as a sponge of miR-27b-3p.

Cancer pathogenesis is influenced by epigenetic alterations mediated by circular RNAs (circRNAs). In this study, we aimed to investigate the regulatory mechanisms and cytological function of hsa_circ_0006470/miR-27b-3p in gastric cancer (GC). circRNA and microRNA expressions in cancer cells were measured by the qRT-PCR method. A dual-luciferase reporter assay was performed to validate the binding of hsa_circ_0006470 with miR-27b-3p. hsa_circ_0006470 was silenced in AGS cells, and proliferation, migration, and invasion were tested via the CCK-8 assay and Transwell system, respectively. The autophagy in GC cells was assessed by marker protein detection and transmission electron microscope. The results showed that hsa_circ_0006470 expression was significantly elevated in GC cells, which was mainly distributed in cytoplasmic components and could directly bind with miR-27b-3p in GC cells. Silencing of hsa_circ_0006470 repressed cell proliferation, migration, and invasion, which may be through regulating miR-27b-3p/Receptor tyrosine kinase-like orphan receptor 1 (ROR1). Silencing of hsa_circ_0006470 also elevated LC3II and Beclin-1 and suppressed p62 protein abundances, which subsequently induced autophagy in AGS cells. Furthermore, we found that hsa_circ_0006470 promotes phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PI3KCA) expressing by sponging miR-27b-3p. In conclusion, hsa_circ_0006470 promoted GC cell proliferation and migration through targeting miR-27b-3p and suppressing autophagy machinery.

MicroRNA 144 inhibits cell migration and invasion and regulates inflammatory cytokine secretion through targeting toll like receptor 2 in non-small cell lung cancer.

INTRODUCTION: MicroRNAs (miRNAs) are endogenous small noncoding RNA molecules involved in modulation of cancer progression. Here, we investigated the possible role of miR-144 in non-small cell lung cancer (NSCLC) development. MATERIAL AND METHODS: The expression of miR-144 and TLR2 in NSCLC tissue and cell lines was determined by quantitative real-time PCR (qPCR). The TargetScan database was used to predict potential target genes of miR-144. Luciferase assay was used to verify the interaction between TLR2 and miR-144. TLR2 protein expression was measured by western blot. The secretion of interleukin (IL)-1ß, IL-6 and IL-8 in A549 cells was detected by an ELISA kit. Cell migration and invasion were evaluated by wound healing assay and transwell assay, respectively. RESULTS: Our results showed that miR-144 was downregulated in NSCLC tissue and cell lines when compared with the normal tissues and cell line (p < 0.05). The protein level of TLR2 in NSCLC tissue and cell lines was significantly higher than that in normal lung tissues. Dual luciferase reporter gene assay showed that miR-144 could bind to the 3'UTR of TLR2 specifically. Up-regulation of miR-144 significantly decreased the expression of TLR2. Up-regulation of miR-144 or down-regulation of TLR2 could decrease cell migration, invasion and secretion of IL-1ß, IL-6 and IL-8 in A549 cells. Moreover, overexpression of TLR2 rescued the inhibitory effects of miR-144 on migration, invasion and inflammatory factor secretion of A549 cells. CONCLUSIONS: miR-144 could inhibit the migration, invasion and secretion of IL-1ß, IL-6 and IL-8 through downregulation of TLR2 expression in A549 cells.

Combined targeting of vascular endothelial growth factor C (VEGFC) and P65 using miR-27b-3p agomir and lipoteichoic acid in the treatment of gastric cancer.

BACKGROUND: Gastric cancer is the second leading cancer-related mortality worldwide and more effective treatment strategies are urgently needed to combat the disease. Using lipoteichoic acid (LTA) and miR-27b-3p agomir, we aimed to assess the efficacy of this combination of therapies in treating gastric cancer. METHODS: The RNA levels of miR-27b-3p, FOXO3, MET, KRAS, vascular endothelial growth factor C (VEGFC), TSC1, and P65 were analyzed by quantified-PCR (Q-PCR) and the cell viability of AGS cells was analyzed by MTT. Confirm Luciferase reporter assays were used to explore the putative miR-27b-3p binding sites and Western blot analyzed the protein level of GAPDH, VEGFC, P65, AKT, and phosphorylated-AKT (p-AKT). The level of P65 in both the cytoplasm and nucleus of AGS cells was visualized by immunofluorescence assay. Subcutaneous xenograft models of gastric cancer were established, and mice were treated with miR-27b-3p agomir, LTA, or both. Hematoxylin-eosin staining and Ki-67 immunohistochemistry analysis of tumor tissues were then performed. RESULTS: The results showed that the decreased expression of miR-27b-3p in gastric cancer cell lines inhibited the viability of AGS cells, and VEGFC was confirmed as the target of miR-27b-3p. In addition, ectopic expression of miR-27b-3p significantly inhibited the AKT pathway in AGS and N87 cells, and LTA suppressed the proliferation of gastric cancer cells by inhibiting the NF-κB pathway. In an established xenograft model, both miR-27b-3p agomir alone and LTA treatment alone inhibited tumor growth and treatment which combined the two showed an even stronger inhibitory effect. CONCLUSIONS: Taken together, the combined use of LTA and miR-27b-3p agomir exhibited a synergistic effect in the treatment of gastric cancer.

LncRNA FAM230B Promotes Gastric Cancer Growth and Metastasis by Regulating the miR-27a-5p/TOP2A Axis.

AIM: Long non-coding RNAs serve as key components of competing endogenous RNA (ceRNA) networks that underlie tumorigenesis. We investigated the pathogenic roles of lncRNA FAM230B and its molecular mechanism in gastric cancer (GC). METHOD: The levels of FAM230B expression in five gastric cancer cell lines and in human gastric mucosal cells were compared by quantitative RT-PCR. To analyze the function of FAM230B in GC, we overexpressed FAM230B in AGS cells, silenced FAM230B in MGC-803 cells, and tested the effect of FAM230B on tumor growth in nude mice. The interaction between miR-27a-5p and FAM230B was predicted by a bioinformatics analysis and then verified with a dual-luciferase reporter assay. We also further investigated the role and mechanism of FAM230B by forcing overexpression of miR-27a-5p in MGC-803 gastric cancer cells. RESULTS: We found that FAM230B was highly expressed in gastric cancer cell lines and mainly located in the cytoplasm. FAM230B overexpression promoted the proliferation, migration, and invasion of AGS cells and repressed their apoptosis; it also facilitated tumor growth in vivo. In contrast, FAM230B knockdown suppressed the proliferation, migration, and invasion of MGC0803 cells, but enhanced their apoptosis and inhibited tumor growth in vivo. MiR-27a-5p expression was suppressed by FAM230B overexpression in AGS cells. MiR-27a-5p inhibited the proliferation, migration, and invasion of gastric cancer cells, and promoted the apoptosis of gastric cancer cells by reducing TOP2A (topoisomerase 2 alpha) expression. CONCLUSION: Our study showed that lncRNA FAM230B might function to promote GC. FAM230B functioned as a ceRNA by sponging miR-27a-5p and enhancing TOP2A expression.

Antiviral activities of resveratrol against rotavirus in vitro and in vivo.

BACKGROUND: Rotavirus (RV) is the primary causative agent for viral gastroenteritis among infants and young children worldwide. Currently, no clinically approved and effective antiviral drug for the treatment of RV infection is available. PURPOSE: We investigated the potential anti-RV activity of resveratrol and underlying mechanisms by which resveratrol acted against RV. METHODS: The anti-RV activity of resveratrol in vitro was evaluated using plaque reduction assays. The effects of resveratrol on yield of virion progeny, viral polyprotein expression and genomic RNA synthesis were respectively investigated using enzyme-linked immunosorbent assays, western blotting and qRT-PCR assays. Further, we also measured the antiviral effect of resveratrol by evaluation of antigen clearance and assessment of changes in proinflammatory cytokines/chemokines in RV-infected neonatal mouse model. RESULTS: Our results indicated that 20 µM of resveratrol significantly inhibited RV replication in Caco-2 cell line by suppressing RV RNA synthesis, protein expression, viroplasm plaque formation, progeny virion production, and RV-induced cytopathy independent of the different strains and cell lines of RV that we used. Analysis of the effect of time post-addition of resveratrol indicated that its application inhibited early processes in the RV replication cycle. Further study of the underlying mechanism of anti-RV activity indicated that resveratrol inhibited RV replication by suppressing expression of heat-shock protein 90 (HSP90) mRNA and protein, and that the effect occurred in a dose-dependent manner. Overexpression of HSP90 was found to have attenuated the inhibitory effect of resveratrol on RV replication. Interestingly, the application of resveratrol were found to down-regulate the level of inhibition of RV-mediated MEK1/2 and ERK phosphorylation. Using a RV-infected suckling mice model, we found that application of resveratrol significantly lessened the severity of diarrhea, decreased viral titers, and relieved associated symptoms. Levels of mRNA expression of interleukin-2, interleukin-10, tumor necrosis factor-α, interferon-γ, macrophage inflammatory protein 1, and monocyte chemotactic protein-1 were all found to have been sharply reduced in intestinal tissue from mice which had been treated with resveratrol (10 or 20 mg/kg) after RV infection (p < 0.05). CONCLUSION: These findings implied that resveratrol exhibits antiviral activity and could be a promising treatment for rotavirus infection.

Effect of quercetin supplementation on plasma lipid profiles, blood pressure, and glucose levels: a systematic review and meta-analysis.

CONTEXT: Clinical trials examining the cardiovascular protective effects of quercetin in humans have reported conflicting results. OBJECTIVE: The aim of this systematic review was to summarize evidence of the effects of quercetin supplementation on plasma lipid profiles, blood pressure (BP), and glucose levels in humans by performing a meta-analysis of randomized controlled trials. DATA SOURCES: MEDLINE, Embase, and Scopus databases were searched electronically from their inception to July 2018 to identify randomized controlled trials that assessed the impact of quercetin on lipid profiles, BP, and glucose levels. STUDY SELECTION: Randomized controlled trials assessing the effects of quercetin or a standardized quercetin-enriched extract on plasma lipid profiles, BP, and glucose levels in humans were eligible for inclusion. DATA EXTRACTION: A random-effects model was used for data analysis. Continuous variables were expressed as weighted mean differences (WMDs) and 95%CIs. Subgroup analyses were conducted to explore possible influences of study characteristics. Sensitivity analyses were also performed, as were analyses of publication bias. RESULTS: Seventeen trials (n = 896 participants total) were included in the overall analysis. Pooled results showed that quercetin significantly lowered both systolic BP (WMD, -3.09 mmHg; 95%CI, -4.59 to -1.59; P = 0.0001) and diastolic BP (WMD, -2.86 mmHg; 95%CI, -5.09 to -0.63; P = 0.01). Neither lipid profiles nor glucose concentrations changed significantly. In subgroup analyses, significant changes in high-density lipoprotein cholesterol and triglycerides were observed in trials with a parallel design and in which participants consumed quercetin for 8 weeks or more. CONCLUSION: Quercetin intake resulted in significantly decreased BP in humans. Moreover, participants who consumed quercetin for 8 weeks or more showed significantly changed levels of high-density lipoprotein cholesterol and triglycerides in trials with a parallel design.

The effects of chitosan supplementation on body weight and body composition: a systematic review and meta-analysis of randomized controlled trials.

Although several clinical trials studied the efficacy of chitosan on weight loss, controversial results have been found. Herein, we evaluated randomized controlled trials (RCTs) of chitosan consumption in adult participants on body weight and body composition through a meta-analysis with trial sequential analysis (TSA). We searched EMBASE, MEDLINE, Web of Science, and CENTRAL databases. The primary body composition indices including body weight, body mass index (BMI), waist circumference, body fat, and hip circumference were extracted. The quality of included articles was assessed according to the Cochrane risk of bias tool. Data were pooled using the random-effects models and calculated as weighted mean difference (WMD) with 95% confidence intervals (CI). Heterogeneity investigated using I2 statistics. TSA, subgroup analyses, sensitivity analysis, meta-regression and publication bias were also evaluated. Overall, 15 eligible trials (18 treatment arms) with 1130 subjects were included. The pooled analyses revealed a significant reduction in body weight (WMD, -0.89 kg; 95% CI, -1.41 to -0.38; P = 0.0006), BMI (WMD, -0.39 kg/m2; 95% CI, -0.64 to -0.14; P = 0.002) and body fat (WMD, -0.69%; 95% CI, -1.02 to -0.35; P = 0.0001) receiving chitosan supplementation. Subgroup analyses also showed that consuming chitosan in dose (>2.4 g/d), shorter-term (<12 weeks), studies with parallel design and studies including participants with obese or overweight had positive effects on body composition. TSA provided conclusive evidence for the benefit of chitosan supplementation. Our findings provided evidence that chitosan consumption might be a useful adjunctive pharmacological therapeutic tool for body weight management particularly in overweight/obese participants. Further well-constructed clinical trials that target body weight and body composition as their primary outcomes are needed.

Clinical effectiveness of quercetin supplementation in the management of weight loss: a pooled analysis of randomized controlled trials.

Purpose: The previous investigations which considered the possible effect of the quercetin supplementation for overweight and obesity have led to inconsistent results. Here, we aimed to evaluate the effects of quercetin on weight loss using a meta-analysis of randomized controlled clinical trials (RCTs). Methods: Relevant studies were systematically searched from the MEDLINE, EMBASE, Google Scholar, and Scopus databases. RCTs that investigated the effects of quercetin on weight loss in humans were included for quality assessment, meta-analyses, sensitivity analysis, subgroup analyses, and publication bias assessment. Effect size was expressed as weighted mean difference (WMD) and 95% CI by using a random-effects model. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to rate the level of evidence. Results: Nine RCTs (11 treatment arms) with 525 participants were finally included for data pooling. Our meta-analysis revealed that daily quercetin supplementation did not significantly affect the body weight (WMD: -0.35 kg, 95% CI: -2.03, 1.33; P=0.68), body mass index (WMD: -0.04 kg/m2, 95% CI: -0.54, 0.45; P=0.87), waist circumference (WMD: -0.37 cm, 95% CI: -1.81, 1.06; P=0.61), and waist to hip ratio (WMD: -0.01, 95% CI: -0.03, 0.01; P=0.48). Subgroup analysis could not identify factors significantly influencing these parameters. These results were robust in sensitivity analysis, and no significant publication bias was found. Conclusion: The current evidence suggests that quercetin intake did not show a notably favorable effect on weight loss. Future well-designed and long-term clinical trials are required to confirm these results.

Effects of coenzyme Q10 on cardiovascular and metabolic biomarkers in overweight and obese patients with type 2 diabetes mellitus: a pooled analysis.

BACKGROUND: The potential effects of coenzyme Q10 (CoQ10) supplementation in overweight/obese patients with type 2 diabetes mellitus are not fully established. In this article, we aimed to perform a pooled analysis to investigate the effects of CoQ10 intervention on cardiovascular disease (CVD) risk factors in overweight/obese patients with type 2 diabetes mellitus (T2DM). METHODS: MEDLINE, Embase, and Cochrane databases were searched for randomized controlled trials that evaluated the changes in CVD risk factors among overweight and obese patients with T2DM following CoQ10 supplementation. Two investigators independently assessed articles for inclusion, extracted data, and assessed risk of bias. Major endpoints were synthesized as weighted mean differences (WMDs) with 95% CIs. Subgroup analyses were performed to check the consistency of effect sizes across groups. Publication bias and sensitivity analysis were also performed. RESULTS: Fourteen eligible trials with 693 overweight/obese diabetic subjects were included for pooling. CoQ10 interventions significantly reduced fasting blood glucose (FBG; -0.59 mmol/L; 95% CI, -1.05 to -0.12; P=0.01), hemoglobin A1c (HbA1c; -0.28%; 95% CI-0.53 to -0.03; P=0.03), and triglyceride (TG) levels (0.17 mmol/L; 95% CI, -0.32 to -0.03; P=0.02). Subgroup analysis also showed that low-dose consumption of CoQ10 (<200 mg/d) effectively reduces the values of FBG, HbA1c, fasting blood insulin, homeostatic model assessment of insulin resistance, and TG. CoQ10 treatment was well tolerated, and no drug-related adverse reactions were reported. CONCLUSION: Our findings provide substantial evidence that daily CoQ10 supplementation has beneficial effects on glucose control and lipid management in overweight and obese patients with T2DM.

Quantifying the effects of spirulina supplementation on plasma lipid and glucose concentrations, body weight, and blood pressure.

PURPOSE: Spirulina is generally used as a nutraceutical food supplement due to its nutrient profile, lack of toxicity, and therapeutic effects. Clinical trials have investigated the influence of spirulina on metabolic-related risk factors but have yielded conflicting results in humans. Here, we summarize the evidence of the effects of spirulina on serum lipid profile, glucose management, BP, and body weight by conducting a meta-analysis. MATERIALS AND METHODS: Relevant studies were retrieved by systematic search of MEDLINE, EMBASE, Scopus databases, and reference lists of relevant original studies from inception to July 2018. Data were extracted following a standardized protocol. Two investigators independently extracted study characteristics, outcomes measures, and appraised methodological quality. Effect sizes were performed using a random-effects model, with weighted mean differences (WMDs) and 95% CIs between the means for the spirulina intervention and control arms. Subgroup analyses were conducted to explore the possible influences of study characteristics. Publication bias and sensitivity analysis were also performed. RESULTS: A total of 1,868 records were identified of which 12 trials with 14 arms were eligible. The amount of spirulina ranged from 1 to 19 g/d, and intervention durations ranged from 2 to 48 weeks. Overall, data synthesis showed that spirulina supplements significantly lowered total cholesterol (WMD = -36.60 mg/dL; 95% CI: -51.87 to -21.33; P=0.0001), low-density lipoprotein cholesterol (WMD = -33.16 mg/dL; 95% CI: -50.52 to -15.75; P=0.0002), triglycerides (WMD = -39.20 mg/dL; 95% CI: -52.71 to -25.69; P=0.0001), very-low-density lipoprotein cholesterol (WMD = -8.02 mg/dL; 95% CI: -8.77 to -7.26; P=0.0001), fasting blood glucose (WMD = -5.01 mg/dL; 95% CI: -9.78 to -0.24; P=0.04), and DBP (WMD = -7.17 mmHg; 95% CI: -8.57 to -5.78; P=0.001). These findings remained stable in the sensitivity analysis, and no obvious publication bias was detected. CONCLUSION: Our findings provide substantial evidence that spirulina supplementation has favorable effect on select cardiovascular and metabolic biomarkers in humans, including lipid, glucose, and DBP management.

Quantitative assessment of the clinical susceptibility of calcium-sensing receptor polymorphisms in cancer patients.

BACKGROUND: Accumulating evidence has suggested a relationship between calcium-sensing receptor (CASR) polymorphisms and cancer risk in different types of cancer; however, the findings from epidemiologic studies have been conflicting. The purpose of this meta-analysis was to assess the clinical susceptibility of CASR polymorphisms in cancer patients. MATERIALS AND METHODS: This study systematically searched MEDLINE and EMBASE databases for eligible articles through March 2017. The strength of association was expressed as odds ratio and 95% CI. Publication bias, heterogeneity, sensitivity analysis, and subgroup analyses were also examined. RESULTS: Fourteen related case-control studies were finally identified to be included in the present analysis. The pooled result showed that no significant associations were found among CASR rs1801725, rs1042636, rs12485716, rs4678174, rs1801726, rs17251221, rs10934578, and rs2270916 polymorphisms and cancer risk under all genetic models (P>0.05). The relationship between CASR rs1801725 polymorphism and risk of cancer was consistent in the subgroup analyses, and robust in sensitivity analysis. No publication bias was presented in our pooled-analysis. CONCLUSION: The current evidence for our pooled analysis suggests that the CASR polymorphisms are not associated with an increased risk of cancer. Further larger studies are still necessary to warrant and validate the findings in the current meta-analysis.

Lipid-Modifying Effects of Chitosan Supplementation in Humans: A Pooled Analysis with Trial Sequential Analysis.

SCOPE: We performed a pooled analysis with trial sequential analysis (TSA) to evaluate the efficacy and safety of chitosan supplementation on serum lipids in humans. METHODS AND RESULTS: Medline, EMBASE, and CENTRAL databases were queried. Impact was expressed as a weighted mean difference (WMD) and 95% confidence interval (CI). Sensitivity analysis was conducted using the leave-one-out method. Statistical heterogeneity, publication bias, TSA, and subgroup analyses were also assessed. Fourteen trials (21 treatment arms) encompassing 1108 participants were suitable for statistical pooling. Chitosan supplementation significantly improved the total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations in all patients. The WMDs were -0.20 mmol L-1 (95% CI, -0.35 to -0.05; p = 0.009) for TC, and -0.20 mol L-1 (95% CI, -0.26 to -0.15; p = 0.0001) for LDL-C, respectively. TSA demonstrated that the cumulative Z-curve crossed the trial sequential monitoring boundary for benefit providing conclusive evidence for the benefit of chitosan. However, no significant changes were seen with high-density lipoprotein cholesterol (HDL-C) and triglycerides. Our findings were robust after sensitivity analyses, and no serious adverse events were reported with chitosan intake. CONCLUSION: Supplementation with chitosan effectively reduces plasma concentrations of TC and LDL-C. Current evidence indicates daily chitosan supplementation as a candidate for therapeutic lipid management strategies.

Quantitative assessment of the effects of chitosan intervention on blood pressure control.

BACKGROUND: Chitosan is a popular dietary fiber often used to reduce dietary fat absorption to control weight and blood lipids. However, its effects on blood pressure (BP) have not been fully elucidated. We evaluated the effects of chitosan administration on systolic blood pressure (SBP) and diastolic blood pressure (DBP) through a pooled analysis of available randomized controlled trials (RCTs). MATERIALS AND METHODS: Electronic searches were conducted in Medline, Cochrane Library, Scopus, and EMBASE to identify relevant human placebo-control RCTs. Trials that reported BP changes from baseline to study endpoint in patients receiving treatment of chitosan were included for analysis. Weighted mean difference (WMD) and 95% CIs were pooled using fixed-effects or random-effects models. Statistical heterogeneity, prespecified subgroup, publication bias, sensitivity analysis, and meta-regression assessments were also tested. RESULTS: Six hundred and seventeen participants from eight trials with 10 arms were included. Overall, chitosan administration did not significantly lower SBP (WMD: -1.41 mmHg, 95% CI: -3.29 to 0.47; P=0.14) and DBP (WMD: -0.61 mmHg, 95% CI: -1.75 to 0.52; P=0.29). However, our subgroup analyses indicated that chitosan consumption significantly reduced DBP in shorter-term (<12 weeks) and higher-dose (>2.4 g/day) arms. Funnel plots or Egger's tests analysis (P=0.36 and 0.43 for SBP and DBP, respectively) demonstrated that there was no significant publication bias in this study. CONCLUSION: This meta-analysis indicates that chitosan consumption significantly decreases DBP at higher dosage and in shorter-term interventions, while chitosan has no significant effects on SBP. However, these results should be interpreted cautiously because of the limited eligible RCTs included in this meta-analysis; further large-scale, well-designed RCTs on this topic are urgently needed.

Chromium supplementation for adjuvant treatment of type 2 diabetes mellitus: Results from a pooled analysis.

SCOPE: We conducted a pooled analysis of randomized controlled trials to evaluate the effects of chromium supplementation on clinically relevant metabolic biomarkers in type 2 diabetes mellitus (T2DM) patients. METHODS AND RESULTS: Electronic searches were conducted and the bibliographies of located articles were searched, and 28 studies were suitable for statistical pooling. Endpoints were calculated as weighted mean differences (WMDs) with 95% confidence intervals (CIs) by using fixed-effects or random-effects models. Statistical heterogeneity, publication bias, subgroup analyses, sensitivity analysis and meta-regression assessments were also assessed. Chromium reduced levels of fasting plasma glucose (WMD, -0.99 mmol/L; 95% CI, -1.72 to -0.25; p = 0.008), hemoglobin A1c (WMD, -0.54 %; 95% CI, -0.82 to -0.25; p = 0.0002), triglycerides (WMD, -11.71 mg/dL; 95% CI, -18.38 to -5.04; p = 0.0006). Chromium also increased levels of high-density lipoprotein cholesterol (WMD, 1.73 mg/dL; 95% CI, 0.50 to 2.96; p = 0.006). These results were robust in sensitivity analysis and were not dependent on the chromium dose and duration of supplementation. Subgroup analyses indicated that these notably favorable effects were presented in T2DM subjects ingesting chromium chloride and chromium picolinate formulations. CONCLUSION: Our pooled analysis suggested that chromium supplementation might be a candidate as an adjunct to pharmacological management in patients with T2DM.