Anticancer Activity of Delphinium semibarbatum Alkaloid Fractions against LNCaP, and DU 145 Human Prostate Cancer Cells through the Intrinsic Apoptotic Pathway.

Prostate cancer is one of the common cancers with a high mortality rate in men. Therefore, there is always a necessity to discover new medications for treatment or alleviating its symptoms. In recent years, anticancer properties of a number of delphinium species were reported, but there is no study on the anticancer effects of Delphinium semibarbatum (D. semibarbatum) alkaloid contents. Therefore, this survey aimed to check the cytotoxicity and apoptotic properties of D. semibarbatum alkaloid fractions (DSAFs) against prostate cancer cells. Cytotoxicity was measured by MTT assay. We examined the apoptosis by detecting annexin V-FITC/PI staining, the mitochondrial membrane potential (ΔΨm) disruption, reactive oxygen species (ROS) generation, the activity of caspase-3, and expression of the Bax and Bcl-2 in cancer cells. DSAFs treatment inhibited the growth of LNCaP and DU-145 cells by the increase of apoptotic (Q2+Q3) cells detected by annexin V/PI assay. We found over-generation of intracellular ROS and ΔΨm loss in mitochondrial membrane potential treated cell lines. Attenuation of anti-apoptotic Bcl-2 followed by the increase in pro-apoptotic Bax bands, as well as activation of the caspase-3 enzyme was shown in Western blot analysis. Phytochemical analysis suggested that hetisine type diterpene alkaloids were probably responsible for apoptotic activities. Conclusively, the present study demonstrated that D. semibarbatum alkaloid content exerted antiproliferative effects against prostate cancer cells by inducing the intrinsic pathway of apoptosis.

Baseline and postoperative levels of C-reactive protein and interleukins as inflammatory predictors of atrial fibrillation following cardiac surgery: a systematic review and meta-analysis.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a leading arrhythmia with high incidence and serious clinical implications after cardiac surgery. Cardiac surgery is associated with systemic inflammatory response including increase in cytokines and activation of endothelial and leukocyte responses. AIM: This systematic review and meta-analysis aimed to determine the strength of evidence for evaluating the association of inflammatory markers, such as C-reactive protein (CRP) and interleukins (IL), with POAF following isolated coronary artery bypass grafting (CABG), isolated valvular surgery, or a combination of these procedures. METHODS: We conducted a meta-analysis of studies evaluating measured baseline (from one week before surgical procedures) and postoperative levels (until one week after surgical procedures) of inflammatory markers in patients with POAF. A compre-hensive search was performed in electronic medical databases (Medline/PubMed, Web of Science, Embase, Science Direct, and Google Scholar) from their inception through May 2017 to identify relevant studies. A comprehensive subgroup analysis was performed to explore potential sources of heterogeneity. RESULTS: A literature search of all major databases retrieved 1014 studies. After screening, 42 studies were analysed including a total of 8398 patients. Pooled analysis showed baseline levels of CRP (standard mean difference [SMD] 0.457 mg/L, p < 0.001), baseline levels of IL-6 (SMD 0.398 pg/mL, p < 0.001), postoperative levels of CRP (SMD 0.576 mg/L, p < 0.001), postoperative levels of IL-6 (SMD 1.66 pg/mL, p < 0.001), postoperative levels of IL-8 (SMD 0.839 pg/mL, p < 0.001), and postoperative levels of IL-10 (SMD 0.590 pg/mL, p < 0.001) to be relevant inflammatory parameters significantly associated with POAF. CONCLUSIONS: Perioperative inflammation is proposed to be involved in the pathogenesis of POAF. Therefore, perioperative assessment of CRP, IL-6, IL-8, and IL-10 can help clinicians in terms of predicting and monitoring for POAF.

Haematological indices as predictors of atrial fibrillation following isolated coronary artery bypass grafting, valvular surgery, or combined procedures: a systematic review with meta-analysis.

BACKGROUND: New postoperative atrial fibrillation (POAF) is one of the most critical and common complications after cardiovascular surgery precipitating early and late morbidities. Complete blood count (CBC) is an imperative blood test in clinical practice, routinely used in the examination of cardiovascular diseases. AIM: This systematic review with meta-analysis aimed to determine the strength of evidence for evaluating the association of haematological indices in CBC tests with atrial fibrillation following isolated coronary artery bypass graft (CABG), isolated valvular surgery, or a combination of these treatments. METHODS: We conducted a meta-analysis of studies evaluating pre- and postoperative haematological indices in patients with POAF. A comprehensive subgroup analysis was performed to explore potential sources of heterogeneity. RESULTS: A literature search of all major databases retrieved 732 studies. After screening, 22 studies were analysed including a total of 6098 patients. Pooled analysis showed preoperative platelet count (PC) (weighted mean difference [WMD] = -7.07 × 10^9/L and p < 0.001), preoperative mean platelet volume (MPV) (WMD = 0.53 FL and p < 0.001), preoperative white blood cell count (WBC) (WMD = 0.130 × 10^9/L and p < 0.001), preoperative neutrophil-to-lymphocyte ratio (NLR) (WMD = 0.33 and p < 0.001), preoperative red blood cell distribution width (RDW) (WMD = 0.36% and p < 0.001), postoperative WBC (WMD = 1.36 × 10^9/L and p < 0.001), and postoperative NLR (WMD = 0.74 and p < 0.001) as associated factors with POAF. CONCLUSIONS: Haematological indices may predict the risk of POAF before surgery. These easily-performed tests should definitely be taken into account in patients undergoing isolated CABG, valvular surgery, or combined procedures.

Prediction of New-Onset and Recurrent Atrial Fibrillation by Complete Blood Count Tests: A Comprehensive Systematic Review with Meta-Analysis.

BACKGROUND Atrial fibrillation (AF) is one of the most critical and frequent arrhythmias precipitating morbidities and mortalities. The complete blood count (CBC) test is an important blood test in clinical practice and is routinely used in the workup of cardiovascular diseases. This systematic review with meta-analysis aimed to determine the strength of evidence for evaluating the association of hematological parameters in the CBC test with new-onset and recurrent AF. MATERIAL AND METHODS We conducted a meta-analysis of observational studies evaluating hematologic parameters in patients with new-onset AF and recurrent AF. A comprehensive subgroup analysis was performed to explore potential sources of heterogeneity. RESULTS The literature search of all major databases retrieved 2150 studies. After screening, 70 studies were analyzed in the meta-analysis on new-onset AF and 23 studies on recurrent AF. Pooled analysis on new-onset AF showed platelet count (PC) (weighted mean difference (WMD)=WMD of -26.39×10^9/L and p<0.001), mean platelet volume (MPV) (WMD=0.42 FL and p<0.001), white blood cell (WBC) (WMD=-0.005×10^9/L and p=0.83), neutrophil to lymphocyte ratio (NLR) (WMD=0.89 and p<0.001), and red blood cell distribution width (RDW) (WMD=0.61% and p<0.001) as associated factors. Pooled analysis on recurrent AF revealed PC (WMD=-2.71×109/L and p=0.59), WBC (WMD=0.20×10^9/L (95% CI: 0.08 to 0.32; p=0.002), NLR (WMD=0.37 and p<0.001), and RDW (WMD=0.28% and p<0.001). CONCLUSIONS Hematological parameters have significant ability to predict occurrence and recurrence of AF. Therefore, emphasizing the potential predictive role of hematological parameters for new-onset and recurrent AF, we recommend adding the CBC test to the diagnostic modalities of AF in clinical practice.

Predictive Role of Coagulation, Fibrinolytic, and Endothelial Markers in Patients with Atrial Fibrillation, Stroke, and Thromboembolism: A Meta-Analysis, Meta-Regression, and Systematic Review.

BACKGROUND The pathophysiological mechanism associated with the higher prothrombotic tendency in atrial fibrillation (AF) is complex and multifactorial. However, the role of prothrombotic markers in AF remains inconclusive. MATERIAL AND METHODS We conducted a meta-analysis of observational studies evaluating the association of coagulation activation, fibrinolytic, and endothelial function with occurrence of AF and clinical adverse events. A comprehensive subgroup analysis and meta-regression was performed to explore potential sources of heterogeneity. RESULTS A literature search of major databases retrieved 1703 studies. After screening, a total of 71 studies were identified. Pooled analysis showed the association of coagulation markers (D-dimer (weighted mean difference (WMD) =197.67 and p<0.001), fibrinogen (WMD=0.43 and p<0.001), prothrombin fragment 1-2 (WMD=0.53 and p<0.001), antithrombin III (WMD=23.90 and p=0.004), thrombin-antithrombin (WMD=5.47 and p=0.004));  fibrinolytic markers (tissue-type plasminogen activator (t-PA) (WMD=2.13 and p<0.001), plasminogen activator inhibitor (WMD=11.44 and p<0.001), fibrinopeptide-A (WMD=4.13 and p=0.01)); and  endothelial markers (von Willebrand factor (WMD=27.01 and p<0.001) and soluble thrombomodulin (WMD=3.92 and p<0.001)) with AF. CONCLUSIONS The levels of coagulation, fibrinolytic, and endothelial markers have been reported to be significantly higher in AF patients than in SR patients.

Platelets Cellular and Functional Characteristics in Patients with Atrial Fibrillation: A Comprehensive Meta-Analysis and Systematic Review.

BACKGROUND This systematic review with meta-analysis aimed to determine the strength of evidence for evaluating the association of platelet cellular and functional characteristics including platelet count (PC), MPV, platelet distribution width (PDW), platelet factor 4, beta thromboglobulin (BTG), and p-selectin with the occurrence of atrial fibrillation (AF) and consequent stroke. MATERIAL AND METHODS We conducted a meta-analysis of observational studies evaluating platelet characteristics in patients with paroxysmal, persistent and permanent atrial fibrillations. A comprehensive subgroup analysis was performed to explore potential sources of heterogeneity. RESULTS Literature search of all major databases retrieved 1,676 studies. After screening, a total of 73 studies were identified. Pooled analysis showed significant differences in PC (weighted mean difference (WMD)=-26.93 and p<0.001), MPV (WMD=0.61 and p<0.001), PDW (WMD=-0.22 and p=0.002), BTG (WMD=24.69 and p<0.001), PF4 (WMD=4.59 and p<0.001), and p-selectin (WMD=4.90 and p<0.001). CONCLUSIONS Platelets play a critical and precipitating role in the occurrence of AF. Whereas distribution width of platelets as well as factors of platelet activity was significantly greater in AF patients compared to SR patients, platelet count was significantly lower in AF patients.

Strategies Preventing Contrast-Induced Nephropathy After Coronary Angiography: A Comprehensive Meta-Analysis and Systematic Review of 125 Randomized Controlled Trials.

This systematic review with meta-analysis sought to determine the strength of evidence for the effects of hydration (sodium bicarbonate [SB] and normal saline [NS]), supplementations ( N-acetylcysteine [NAC] and vitamin C), and some common drugs (adenosine antagonists [AAs], statins, loop diuretics, and angiotensin-converting enzyme inhibitors [ACEIs]) on the incidence of contrast-induced nephropathy (CIN) and requirement for hemodialysis after coronary angiography. After screening, a total of 125 trials that reported outcomes were identified. Pooled analysis indicated beneficial effects of SB versus NS (odds ratio [OR] = 0.73; 95% confidence interval [CI]: 0.56-0.94; P = .01), NAC (OR = 0.79; 95% CI: 0.70-0.88; P = .001), vitamin C (OR = 0.64; 95% CI: 0.45-0.89; P = .01), statins (OR = 0.45; 95% CI: 0.35-0.57; P = .001), AA (OR = 0.28; 95% CI: 0.14-0.47; P = .001), loop diuretics (OR = 0.97; 95% CI: 0.33-2.85; P = .9), and ACEI (OR = 1.06; 95% CI: 0.69-1.61; P = .8). Overall, hydration with SB, use of supplements, such as NAC and vitamin C, and administration of statins and AA should always be considered for the prevention of CIN after coronary angiography.

Impact of antioxidant supplementations on cardio-renal protection in cardiac surgery: an updated and comprehensive meta-analysis and systematic review.

This systematic review with meta-analysis sought to determine the strength of evidence in terms of the impact of common antioxidant supplementations, such as N-acetylcysteine (NAC), vitamin C, and polyunsaturated fatty acids (PUFA) on perioperative outcomes after cardiac surgery with particular focus on the incidence of atrial fibrillation (AF) and acute kidney injury (AKI) with associated mortality. A total of 29 trials were identified that reported incidence of AF and 17 trials that reported incidence of AKI. Pooled analysis reported that NAC (OR=0.5; P=.001), vitamin C (OR=0.4; P=.001), and PUFA (OR=0.8; P=.01) administration were associated with significantly reduced incidence of AF. In terms of postoperative AKI, only NAC was shown to be a beneficial supplement that was able to significantly reduce the incidence of AKI (OR=0.7; P=.01), and NAC could also significantly decrease overall mortality (OR=0.3; P=.03) following cardiac surgery. The use of NAC in patients undergoing cardiac surgery should be strongly recommended due to its combined cardio-renal protective effects and reduced mortality. Also, PUFA and vitamin C might be able to significantly decrease the incidence of arrhythmia; however, reno-protective effects and impact on overall mortality of these supplements seem to be less impressive.

Transplantation of bone marrow stem cells during cardiac surgery.

BACKGROUND: This systematic review with meta-analysis sought to determine the efficacy and safety of intramyocardial transplantation of bone marrow stem cells during coronary artery bypass graft surgery on postoperative cardiac functional parameters such as left ventricular ejection fraction and left ventricular end-diastolic volume. METHODS: Medline/PubMed, Embase, Elsevier, Sciences online database, and Google Scholar literature search were searched. The effect sizes measured were risk ratio for categorical variables and weighted mean difference with 95% confidence interval for calculating differences between mean values of baseline and follow-up cardiac functional parameters. A value of p < 0.1 for Q test, or I(2 )> 50%, indicated significant heterogeneity among studies. The literature search retrieved 2900 studies from screened databases, of which 2866 (98.6%) were excluded and 34 (619 patients) were included for scoping review. The final analysis included 9 studies (335 patients). RESULTS: Pooled effects estimates of left ventricular ejection fraction and left ventricular end-diastolic volume showed that bone marrow stem cell transplantation had a weighted mean difference of 4.06 (95% confidence interval: 0.41-7.72; p = 0.02) and 7.06 (95% confidence interval: -8.58-22.7; p = 0.3), respectively. CONCLUSIONS: Intramyocardial transplantation of bone marrow stem cells improves cardiac functional parameters, significantly increasing left ventricular ejection fraction with a nonsignificant reduction in left ventricular end-diastolic volume. Also, this therapeutic method has no life-threatening complications and was therefore found to be an effective and safe method.