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1.
Vitamin D Treatment Attenuates Heart Apoptosis After Coronary Artery Bypass Surgery: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial.
Tasdighi, E, Hekmat, M, Beheshti, M, Baghaei, R, Mirhosseini, SM, Torbati, P, Pourmotahari, F, Foroughi, M
Journal of cardiovascular pharmacology and therapeutics. 2020;(4):338-345
Abstract
BACKGROUND Vitamin D plays an important role in immune system and in the regulation of inflammatory cytokines. Coronary artery bypass graft (CABG) with cardiopulmonary bypass (CPB) is associated with an extensive inflammatory response. The aim of this study is to examine the effect of vitamin D treatment on the apoptosis and inflammatory changes developed after CABG. METHODS This trial was conducted on 70 patients undergoing CABG with CPB. Patients were randomly administered either in placebo or in the group of orally consuming 150 000 IU vitamin D daily for 3 consecutive days before surgery. The right atrium sample was taken to assess caspases 2, 3, and 7 activity using immunohistochemistry method. The serum level of interleukin-10 (IL-10) and insulin-like growth factor 1 (IGF-1) were compared at intervals. RESULTS The average number of positive cells for caspases 2 and 3 were less in vitamin D group (P = .006 and P < .001, respectively). There was an increase in serum levels of IL-10 after 3 days from vitamin D treatment before surgery (vitamin D group = 4.4 ± 4.9 ng/mL and control group = 1 ± 0.5 ng/mL, P = .001). After operation, IL-10 increased in both groups, higher level in vitamin D group (P < .001). The comparison of serum IGF-1 showed significant difference after 3 days (P = .006) and remained higher in vitamin D group after CPB (P < .001). CONCLUSIONS These findings suggest the apoptosis rate after CPB can be reduced by vitamin D. Vitamin D treatment may improve the inflammatory status before and after surgery. Further studies are needed to confirm the antiapoptotic property of vitamin D and clinical implication.
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2.
Comparative Effects of Monosialoganglioside versus Citicoline on Apoptotic Factor, Neurological Function and Oxidative Stress in Newborns with Hypoxic-Ischemic Encephalopathy.
Liang, SP, Chen, Q, Cheng, YB, Xue, YY, Wang, HJ
Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 2019;(4):324-327
Abstract
OBJECTIVE To determine the comparative effect of monosialoganglioside versus citicoline on the content changes of serum apoptotic factors (PDCD5, sFas and sFasL), neurological function indices (BDNF, NSE, S100-β and NGF) and oxidative stress indices (SOD, MDA and GSH-PX) in newborns with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN An experimental study. PLACE AND DURATION OF STUDY Emergency Department, Affiliated Children's Hospital of Zhengzhou University, China, from October 2016 to February 2018. METHODOLOGY A total of 90 newborns with HIE were randomly divided into a treatment group and a control group, with 45 cases in each group. In addition to the conventional treatment, the treatment group was given monosialoganglioside treatment, while the control group was given citicoline treatment. Both groups were treated for 10 days. After treatment, the content differences of serum apoptosis factors (PDCD5, sFas and sFasL), neurological function indices (BDNF, NSE, S100-β and NGF) and oxidative stress indices (SOD, MDA and GSH-PX) were observed in the two groups. RESULTS After treatment, the levels of serum PDCD5, sFas, sFasL, MDA, NSE and S100-β in the treatment group were lower than those in the control group (all p<0.001). The contents of serum SOD, GSH-PX, BDNF and NGF in the treatment group were higher than those in the control group (all p<0.001). CONCLUSION Monosialoganglioside can effectively improve the apoptotic factors, neurological function and oxidative stress indices in newborns and maintain the stability of the internal environment, so it is worthy of promotion and application.
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3.
Effect of dietary supplementation with a highly pure and concentrated docosahexaenoic acid (DHA) supplement on human sperm function.
González-Ravina, C, Aguirre-Lipperheide, M, Pinto, F, Martín-Lozano, D, Fernández-Sánchez, M, Blasco, V, Santamaría-López, E, Candenas, L
Reproductive biology. 2018;(3):282-288
Abstract
The aim of this study was to evaluate the possible beneficial effects of diet supplementation with a highly concentrated and purified docosahexaenoic acid (DHA) formula on human sperm function. We performed a prospective, randomized, double blind, placebo-controlled intervention study. One-hundred eighty human semen samples from sixty infertile patients recruited in a private assisted reproduction center were included. All samples were examined according to World Health Organization guidelines. We analyzed macroscopic and microscopic sperm parameters, oxidative stress, apoptosis, lipid peroxidation, mitochondrial membrane potential and DNA fragmentation before and after supplementation with different DHA daily doses (0.5, 1 and 2 g) or placebo for 1 and 3 months. No differences were found in traditional sperm parameters except for progressive sperm motility, with a significant increase after DHA ingestion after the first month with 1 or 2 g doses and after 3 months with 0.5 g of DHA. This effect was more evident in asthenozoospermic patients. No differences were found in any molecular semen parameter except oxidative stress, in which a slight benefit was observed after DHA treatment. In conclusion, this study support previous indications that highlight the importance of DHA supplementation as a means of improving sperm quality in asthenozoospermic men.
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4.
Influence of Creatine Supplementation on Apoptosis Markers After Downhill Running in Middle-Aged Men: A Crossover Randomized, Double-Blind, and Placebo-Controlled Study.
Sheikholeslami-Vatani, D, Faraji, H
American journal of physical medicine & rehabilitation. 2018;(11):825-831
Abstract
OBJECTIVE Strenuous exercise can induce apoptosis in a variety of tissues. We investigated the effects of creatine loading on apoptosis markers after downhill running. DESIGN Twenty-two middle-aged men were randomly assigned to either a creatine or a placebo group. Crossover design, double-blind controlled supplementation was performed using 20 g/d(-1) of creatine or maltodextrin for 7 days. Downhill running (12% incline) at 70% of heart rate maximum for 40 mins was performed on the eighth day. Blood samples were taken on the day before supplementation, after supplementation and after running. RESULTS There were no significant changes in the caspase-3, caspase-9, p53, Bax, and IGF-1 concentrations from presupplementation to postsupplementation in both groups of creatine and placebo (P > 0.05). There were significant increases (P < 0.05) in serum caspase-3, caspase-9, p53, and Bax after running in the placebo group. These markers were not noticeably changed in the creatine group (P > 0.05). Bcl-2 was unchanged in the placebo group but substantially increased (P < 0.05) in the creatine group. No significant changes were observed in IGF-1 concentration after running comparing to prerunning in both groups (P > 0.05). Lactate levels increased similarly in both groups (P < 0.05). CONCLUSIONS The findings indicate that creatine supplementation could prevent exercise-induced apoptotic markers.
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5.
Effects of bayberry juice on inflammatory and apoptotic markers in young adults with features of non-alcoholic fatty liver disease.
Guo, H, Zhong, R, Liu, Y, Jiang, X, Tang, X, Li, Z, Xia, M, Ling, W
Nutrition (Burbank, Los Angeles County, Calif.). 2014;(2):198-203
Abstract
OBJECTIVE Oxidative stress and inflammation are involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Bayberries contain high levels of polyphenols that possess antioxidative and anti-inflammatory properties in vitro. The purpose of this study was to investigate whether the consumption of bayberry juice beneficially alters the levels of oxidative, inflammatory, and apoptotic biomarkers in young individuals with features of NAFLD. METHODS In this randomized, placebo-controlled, double-blind, crossover study, 44 participants (ages 18-25 y) were given 250 mL of either bayberry juice or placebo twice daily for 4 wk. Several anthropometric characteristics were measured, and fasting blood samples were drawn before and after each intervention period. The levels of plasma glucose, insulin, lipids, and some NAFLD-related biomarkers were determined. RESULTS No significant effects on the anthropometric parameters and the homeostasis model assessment for insulin resistance were observed. Compared with placebo, the consumption of bayberry juice significantly decreased the plasma levels of protein carbonyl groups (P = 0.038), tumor necrosis factor-α (P < 0.001), and interleukin-8 (P = 0.022). The apoptosis markers analysis revealed significant differences between the treatment and the placebo in the levels of tissue polypeptide-specific antigen (P < 0.001) and cytokeratin-18 fragment M30 (P < 0.001). CONCLUSION The consumption of bayberry juice for a period of 4 wk can protect against NAFLD in young adults by improving the plasma antioxidant status and inhibiting the inflammatory and apoptotic responses that are involved in this disease.
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6.
High-dose insulin therapy reduces postoperative liver dysfunction and complications in liver resection patients through reduced apoptosis and altered inflammation.
Fisette, A, Hassanain, M, Metrakos, P, Doi, SA, Salman, A, Schricker, T, Lattermann, R, Wykes, L, Nitschmann, E, Smith, J, et al
The Journal of clinical endocrinology and metabolism. 2012;(1):217-26
Abstract
CONTEXT An exaggerated inflammatory response in patients undergoing major liver resection coupled with poor nutrition diminishes liver regenerative capacity and increases the risk of postoperative complications. OBJECTIVES Our objective was to evaluate the biological context leading to better clinical outcomes in patients undergoing liver resection coupled with hyperinsulinemic-normoglycemic clamp vs. standard care (insulin sliding care). DESIGN AND SETTING This study was a fundamental research analysis of a patient subset from a randomized-controlled study at the McGill University Health Center. PATIENTS AND INTERVENTION Thirty consenting patients participating in a randomized clinical trial for liver resection received either hyperinsulinemic-normoglycemic clamp technique with 24-h preoperative carbohydrate load (intervention) or standard glucose control through insulin sliding scale treatment (control). MAIN OUTCOME MEASURES Liver biopsies and plasma samples were taken at various time points before and after surgery. Primary measures included mRNA quantitation for genes related to insulin signaling, inflammation, and proliferation; proinflammatory cytokines at various time points; and liver function markers. These measurements were associated with clinical outcomes. RESULTS The hyperinsulinemic-normoglycemic clamp technique reduced postoperative liver dysfunction, infections, and complications. Markers of energy stores indicated higher substrate availability. Cytokine expression pattern was altered (TNF-α, IL-8, monocyte chemoattractant protein-1, IL-6, IL-10, and C-reactive protein). Apoptosis was markedly reduced, whereas the complement system was unaltered. CONCLUSION The hyperinsulinemic-normoglycemic clamp technique reduced postoperative negative outcomes by suppressing apoptosis. This phenomenon appears to be linked with higher substrate availability and altered cytokine secretion profile and may provide a long-term benefit of this therapy on liver resection patients.
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7.
Endothelial antioxidant compound prolonged the endothelial antiapoptotic effects registered after tadalafil treatment in patients with arterial erectile dysfunction.
La Vignera, S, Condorelli, R, Vicari, E, D'Agata, R, Calogero, AE
Journal of andrology. 2012;(2):170-5
Abstract
This study evaluated the effects of a chronic treatment with tadalafil, a specific phosphodiesterase V inhibitor, on endothelial apoptosis through changes in the serum concentration of endothelial microparticles (EMP). EMPs were arbitrarily chosen as a marker of endothelial apoptosis, and the changes in their concentration were monitored before and after treatment. Additionally, administration of endothelial antioxidant compound (EAC) during the follow-up, after discontinuation of tadalafil, was evaluated to determine whether this treatment improved the potential effects of tadalafil on the endothelium. Seventy-five patients with arterial erectile dysfunction were evaluated at baseline and after administration of tadalafil (5 mg once daily for 90 days). The International Index of Erectile Function questionnaire was administered, and penile dynamic Doppler and flow-cytometric (serum concentrations of EMPs) analyses were performed before (T0) and after treatment. Time points after tadalafil discontinuation: T1, after 1 week; T2, after 3 months; and T3, after 6 months. Three different schemes of follow-up were evaluated: group A, follow-up with EAC administration, after tadalafil discontinuation, for 6 months; group B, follow-up without other treatment; and group C, follow-up with placebo during the follow-up, after tadalafil cessation. The events CD45(neg)/CD144(pos)/annexinV(pos) were defined EMPs. Patients treated with tadalafil showed a significant decrease in serum EMPs 1 week after discontinuing tadalafil (16.4% ± 3.6% vs 7.1% ± 3.3%). This effect was maintained for up to 3 months in the group without other treatment during follow-up and was maintained for up to 6 months in the group treated with EAC during follow-up. Chronic treatment with tadalafil reduces endothelial apoptosis in patients with arterial erectile dysfunction. Further, EAC treatment prolongs and stabilizes the duration of antiapoptotic effects on the endothelium that are initially promoted by tadalafil treatment.
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8.
Mediterranean diet reduces senescence-associated stress in endothelial cells.
Marin, C, Delgado-Lista, J, Ramirez, R, Carracedo, J, Caballero, J, Perez-Martinez, P, Gutierrez-Mariscal, FM, Garcia-Rios, A, Delgado-Casado, N, Cruz-Teno, C, et al
Age (Dordrecht, Netherlands). 2012;(6):1309-16
Abstract
This paper aims to study the effects of the oxidative stress induced by quality and quantity of dietary fat on cellular senescence. Twenty elderly subjects consumed three diets, each for 4 weeks: a saturated fatty acid diet (SFA), a low-fat and high-carbohydrate diet (CHO-ALA), and a Mediterranean diet (MedDiet) enriched in monounsaturated fatty acid following a randomized crossover design. For each diet, we investigated intracellular reactive oxidative species (ROS), cellular apoptosis and telomere length in human umbilical endothelial cells incubated with serum from each patient. MedDiet induced lower intracellular ROS production, cellular apoptosis, and percentage of cell with telomere shortening, compared with the baseline and with SFA and CHO-ALA diets. Dietary fat modulates the oxidative stress in human endothelial cells. MedDiet protects these cells from oxidative stress, prevents cellular senescence and reduces cellular apoptosis.
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9.
A clinical study on regional lymphatic chemotherapy using an activated carbon nanoparticle-epirubicin in patients with breast cancer.
Yang, Q, Wang, XD, Chen, J, Tian, CX, Li, HJ, Chen, YJ, Lv, Q
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2012;(6):2341-8
Abstract
The purpose of this study was to understand the short-term therapeutic effects of an activated carbon nanoparticle-epirubicin suspension for regional lymphatic chemotherapy in patients with breast cancer. One hundred and twenty patients with stage I, II, or III primary breast cancer were randomly divided into three groups: the lymphatic chemotherapy group using the activated carbon nanoparticle-epirubicin suspension, the epirubicin control group, and the activated carbon control group. Each group of 40 patients was further divided into two subgroups with the drug injected either 24 or 48 h before surgery. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay was used to determine cancer cell apoptotic indices in metastatic lymph nodes. The epirubicin concentration in the black-stained lymph nodes in the lymphatic chemotherapy treatment group was 4,144.64 ± 2,426.44 ng/g, which is significantly higher than in the epirubicin control group (335.87 ± 212.82 ng/g, P < 0.001). The plasma epirubicin concentrations at 0.5, 1.5, and 24 h postinjection in the regional lymphatic chemotherapy treatment group were significantly lower than in the epirubicin control group (P < 0.001). Tolerable mild pain was observed at the injection area after administration of the epirubicin-activated carbon nanoparticle suspension. No regional necrosis or adverse effects were found. The TUNEL assay demonstrated that there was no significant difference in the apoptotic indices in the metastatic lymph nodes from the three groups. Performing lymphatic chemotherapy by regionally injecting the epirubicin-activated carbon nanoparticle suspension could significantly enhance the drug concentration in the stained lymph nodes and lower the plasma drug concentration. The epirubicin-activated carbon nanoparticle suspension has the ability to release the drug slowly in the lymph nodes and, as a result, can prolong the chemotherapeutic effects.
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10.
Leukocyte apoptosis and pro-/anti-apoptotic proteins following downhill running.
Park, KS, Sedlock, DA, Navalta, JW, Lee, MG, Kim, SH
European journal of applied physiology. 2011;(9):2349-57
Abstract
The purposes of this study were to determine the effect of eccentric exercise-induced muscle damage on the induction of apoptosis in peripheral blood leukocytes and to investigate if the elevation in apoptotic leukocytes was mediated by changes in the concentration of anti-/pro-apoptotic proteins in circulation. Twelve moderately trained subjects performed three 40 min treadmill runs at ~70% VO(2max): a level run (L) followed by two downhill runs (DH1 and DH2). Blood samples were taken at rest (PRE) and immediately (POST), 2, 24, and 48 h after each run. Data were analyzed using two-way repeated measures analysis of variance with post hoc Tukey tests. Creatine kinase (CK) activity was significantly elevated at 24 and 48 h following DH1 (P < 0.01). The proportion (%) of apoptotic leukocytes was significantly elevated at POST and 2 h following all three runs, and up to 48 h following DH1 (P < 0.01). Bax at 24-h post and Bax/Bcl-2 ratio at 24- (P < 0.01) and 48-h post (P < 0.05) following DH1 were greater than PRE (P < 0.05). An acute bout of moderate intensity downhill running altered CK activity, Bax concentration and the Bax/Bcl-2 ratio in circulating leukocytes resulting in a greater apoptotic response at 24- and 48-h post-exercise compared to level grade running or a second downhill run. Although the mechanism by which these proteins are altered by unaccustomed eccentric exercise is currently unknown, the differential response to DH1 versus L and DH2 indicates that it may be related to exercise-induced muscle damage.