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MMP-2 and MMP-9 play an important role in pathogenesis of chronic liver diseases, participating in the processes of inflammation and fibrosis. Their role in progression of non-alcoholic fatty liver disease (NAFLD) is poorly understood. Analysis of MMP-2, -9 levels in the blood plasma of patients with different forms of NAFLD [liver steatosis (LS) and non-alcoholic steatohepatitis (NASH) of weak (-WA), moderate (MA), high (-HA) activity without pronounced fibrosis] was performed. Correlations between the levels of MMP-2, -9 and mRNA of the genes MMP2 , MMP9 , ADAM17 , NLRP3 , caspase 3 activity in peripheral blood leukocytes (PBL), TNFα, IL-6, sIL-6R, cytokeratin-18 fragments in plasma were assessed. In steatosis, the levels of MMP2 gene mRNA in PBL and MMP-2 in plasma are lower than in the control, and expression of the NLRP3 gene in PBL is increased relative to other groups. In the NASH-WA, the level of MMP-9 is higher than in the control, in LS, and in NASH-MA, which could be associated with activation of inflammation during transformation of LS into NASH. The plasma level of MMP-9 over 389.50 pg/ml has been shown to be diagnostically significant for identification of NASH-WA among the patients with steatosis ( AUC ROC  = 0.818, 95% CI = 0.689-0.948, p  < 0.001). In NAFLD, the level of MMP-9 could be associated not only with inflammation, but also with apoptosis. ADAM17 probably plays a certain role in this regard. In the advanced NASH, hepatocyte apoptosis is increased, the level of caspase 3 activity in PBL is increased, the level of MMP-9 in the blood is reduced to the level of the control and LS. In the NASH-HA, the level of mRNA of the ADAM17 gene in PBL is increased compared to the control, NASH-WA, and NASH-MA. Thus, MMP-2 and MMP-9 are involved in pathogenesis of NAFLD already at the early stages and their level in blood could be associated with the presence and severity of inflammation in the liver parenchyma.

Objectives: We aimed to assess the serum levels of caspase-3 as a marker of apoptosis and microtubule-associated protein 1A/1B-light chain 3 (MAP1-LC3) as an autophagy marker in epileptic children with various clinical and pharmacological types., Methods: This case-control study was carried out on 90 participants (50 pediatric patients with epilepsy and 40 healthy matched children), the patients were categorized into three groups: Group (A): 25 pharmacosensitive epilepsy, Group (B): 25 pharmacoresistant epilepsy, and Group (C): 40 (age, sex, and body mass index) matched healthy children selected as controls. Serum caspase-3 and MAP1-LC3 were measured in all study groups, using commercially available ELISA kits., Results: Serum caspase-3 was significantly higher among epileptic children, especially in the pharmacoresistant group, cases managed with multiple antiepileptic drugs, and cases with abnormal EEG findings. Conversely, circulating MAP1-LC3 levels showed a significant reduction in epilepsy cases, particularly in pharmacoresistant cases, in cases treated with multiple antiepileptic drugs, and in cases with abnormal EEG data. A significant negative correlation between serum caspase-3 and MAP1-LC3 was found among epileptic children ( r  =  -0.369, p  = 0.0083). Serum caspase-3 was a more valid biomarker in helping diagnose childhood epilepsy, while serum MAP1-LC3 was more valid in predicting pharmacoresistant type., Conclusion: The study reveals that serum caspase-3 levels were significantly elevated, particularly in pharmacoresistant cases and those managed with multiple drugs. Conversely, MAP1-LC3 levels were significantly reduced in epilepsy cases, suggesting potential involvement of altered apoptosis and autophagy in childhood epilepsy., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction: Intermittent hypoxemia has an important role in the physiopathogenesis of obstructive sleep apnea (OSA) complications. Increased apoptosis due to intermittent hypoxemia may be an important clinical entity in OSA. In this study, we aimed to evaluate caspase-3 enzyme level, which is an indirect marker of increased apoptosis in patients with OSA and to evaluate the effect of OSA treatment with continuous positive airway pressure on caspase-3 enzyme level., Materials and Methods: This study included 141 consecutive patients admitted to the sleep-disordered breathing laboratory within 6 months. Caspase-3 was measured in routine blood samples obtained on the morning of polysomnography (PSG) performed at night. The compliance of the patients to CPAP treatment was evaluated and caspase-3 levels were checked again after treatment., Results: A total of 141 patients, 39 females (27,7%) and 102 males (72,3%) were included in the study. The mean age of the patients was 49 ± 12 years (min-17, max-77). According to PSG results, OSA was detected in 95.7% (135/141) of the cases. Mild OSA was 35 (24.8%), moderate OSA 39 (27.7%) and severe OSA 61 (43.3%) cases. Median caspase-3 enzyme levels were similar in men and women in the study group. There was no statistically significant difference in hemogram parameters and caspase-3 enzyme levels between the groups divided according to the presence and severity of OSA. It was determined that caspase-3 enzyme level did not change significantly after 3 months of CPAP treatment in OSA compared to pretreatment. Caspase-3 was found to have a negative correlation with both the percentage of daily use of CPAP therapy and the percentage of CPAP device use for more than 1 h per night. It was found that the control caspase-3 level decreased statistically significantly as the percentage of daily use of CPAP therapy increased (r = -0.397, p = 0.030). It was found that the control caspase-3 level decreased statistically significantly as the percentage of CPAP therapy use for more than 1 h per night increased (r = -0.411, p = 0.024)., Conclusion: The results of this study did not reveal a relationship between the severity of OSA and caspase-3 levels. However, blood caspase-3 levels decreased as treatment compliance increased, suggesting that CPAP treatment may correct increased apoptosis in OSA. There is a need for more comprehensive studies on this issue., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Caspases are key players in the apoptotic process and have been found to contribute to the pathogenesis of a variety of diseases, including neurological disorders such as ischemic stroke. This study aimed to investigate the serum levels of Caspase-3 in patients with acute ischemic stroke (AIS) and in control patients without ischemic events. Moreover, we explored any potential associations with the clinical outcomes of AIS. We enrolled 69 consecutive patients with clinical signs and symptoms of AIS in the presence of a negative CT scan who presented themselves at the Clinical Neurological Department from the Emergency Clinical Hospital of Galati within the first 24 h of symptom onset. The control group comprised 68 patients without cerebral ischemic pathologies. A comparison of the two groups showed significantly higher levels of caspase-3 at 24 and 48 h after hospital admission. No significant associations between caspase-3 levels and clinical features of AIS were seen. However, in a subgroup analysis conducted on patients with moderate/severe and severe stroke, lower levels of caspase-3 were associated with early mortality. Caspase-3 levels did not directly correlate with AIS severity or prognosis when considering all AIS patients. In patients with moderate to severe National Institute of Health Stroke Scale (NIHSS) scores, caspase-3 might be a prognostic indicator of early death. Further studies are required to confirm these results and further explore the mechanisms behind these findings.

Purpose: Neurotoxicity concerns have been raised over general anesthesia and sedation medication use in children. Such concerns are largely based on animal studies, historical anesthetic agents, and assessment tools, thus warranting further investigations. Blood biomarkers in detecting neuronal inflammation and apoptosis are novel methods for detecting neuronal damage. Therefore, the aim of this feasibility study was to assess the usefulness of the levels of four plasma biomarkers in dental general anesthesia (DGA) as surrogate markers of neurotoxicity in children. The secondary aim was to compare changes in motor manipulative skills pre- and post-anesthetic exposure., Methods: This single-center prospective observational study included 22 healthy children aged between 3 and 6 years old who underwent DGA. Subclinical neurotoxicity was measured with a panel of four plasma biomarkers: Caspase-3, neuron-specific enolase (NSE), neurofilament light chain, and S100B at three time points (1; at start, 2; end and 3; on recovery from DGA). The Skillings-Mack test was used to identify the difference in the biomarker levels at three time points. Motor manipulative score assessment, prior and two weeks after DGA was also performed., Results: A total of 22 study participants (mean age = 5 ± 1 years) were included with a median DGA duration of 106 ± 28 min. A reduction in Caspase-3 levels was recorded, with pairwise comparison over three time points, reporting a statistical significance between time point 2 vs. 1 and time point 3 vs. 1. Although fluctuations in NSE levels were recorded, no significant changes were found following pairwise comparison analysis. Among other biomarkers, no significant changes over the three periods were recorded. Furthermore, no significant changes in manipulative motor scores were reported., Conclusion: Caspase-3 reduced significantly in the short time frames during day-care DGA; this might be due to the relatively short anesthesia duration associated with dental treatment as compared with more extensive medical-related treatments. Therefore, further studies on Caspase-3 as a potential biomarker in pediatric DGA neurotoxicity are required to further ascertain results of this study., (© 2024. The Author(s).)

Aim: This study aimed to estimate and correlate the serum and gingival crevicular fluid (GCF) levels of caspase-3 and milk fat globule-epidermal growth factor 8 (MFG-E8) in healthy, gingivitis and generalised chronic periodontitis subjects., Materials and Methods: A total of 24 subjects were selected and divided into three groups. After recording the periodontal parameters (plaque index (PI), modified gingival index (MGI), probing depth (PD) and clinical attachment level (CAL)), the serum and GCF samples were collected and the levels of caspase-3 and MFG-E8 were estimated using enzyme-linked immunoassay (ELISA)., Results: The mean values of PI, MGI, PD and CALs were significantly higher in group III when compared to group II and group I. The mean value of serum and GCF caspase-3 increased with increasing disease severity, whereas the mean serum and GCF values of MFG-E8 decreased with increasing severity of disease. Spearman's correlation showed a strong positive correlation between the serum and GCF levels of caspase-3 and periodontal parameters, whereas serum and GCF levels of MFG-E8 showed a strong negative correlation with the periodontal parameters., Conclusion: The findings of this study are suggestive that the serum and GCF levels of caspase-3 and MFG-E8 could serve as a potential biomarker for the role of apoptosis in periodontal disease. However, further studies are required to explore the mechanism and understand the relationship between these apoptotic markers and periodontitis., (Copyright © 2024 Copyright: © 2024 Indian Journal of Dental Research.)

Background: Apoptosis is central in both diabetes and atherosclerosis, linked to pancreatic beta cell death and plaque progression. Circulating Caspase-3 has also been associated with diabetes and coronary calcium score. Here, we explored if soluble Caspase-3 (sCaspase-3) is associated with cardio-metabolic risk factors and predicts incidence of diabetes and coronary artery disease (CAD)., Methods: Clinical data and plasma from 4637 individuals from the Malmö Diet and Cancer cohort were studied. Plasma sCaspase-3 was measured by a Proximity Extension Assay. National registers were used to identify diabetes and CAD events during follow-up. Type 2 diabetes risk variants and expression quantitative trait loci (eQTL) for sCaspase-3 were retrieved from the DIAGRAM consortium and the Genotype-Tissue Expression project., Results: HbA1c was the factor with the strongest association with sCaspase-3 (r = 0.18, P = 1.3x10 -36 ). During follow-up 666 individuals developed diabetes and 648 individuals suffered from CAD. Increasing sCaspase-3 was associated with a higher risk of developing diabetes (hazard ratio (HR) 1.18 per 1unit; P = 7 × 10 -5 ) and CAD (HR 1.2 per 1 unit, P = 1 × 10 -4 ) during follow-up. A genetic variant rs60780116, located upstream of CASP3, showed strong association with type 2 diabetes (OR 1.06, 95%CI 1.04-1.07, P = 8.4 × 10 -11 ). An eQTL was identified between this variant and gene expression of CASP3, where the allele positively correlated with type 2 diabetes was associated with increased CASP3 expression in blood., Conclusions: The present study provides evidence for plasma sCaspase-3 as a marker of cardio-metabolic risk factors and as a predictor of future diabetes and CAD in a cohort without cardiovascular disease or diabetes at baseline., (© 2021 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: General anesthesia has been associated with neuronal apoptosis and activation of caspases. Apoptosis is a crucial factor in early brain injury following aneurysmal subarachnoid hemorrhage (aSAH). We conducted a double-blind, prospective, randomized pilot study to evaluate the effect of 4 anesthetic agents on cerebrospinal fluid (CSF) and serum caspase-3 levels in aSAH patients., Materials and Methods: A total of 44 good-grade aSAH patients with preoperative lumbar drain scheduled for surgical clipping or endovascular coiling were randomized to receive maintenance of anesthesia with propofol, isoflurane, sevoflurane, or desflurane. Caspase-3 levels were measured in CSF and serum samples collected at baseline, 1 hour after induction, and 1 hour after cessation of anesthesia., Results: Compared with baseline, there was a decrease in CSF caspase-3 levels and an increase in serum caspase-3 levels 1 hour after exposure to all 4 anesthetic agents; levels returned to baseline values after cessation of anesthesia. Median CSF caspase-3 levels at baseline, 1 hour after anesthesia exposure, and 1 hour after cessation of anesthesia were 0.0679, 0.0004, and 0.0689 ng/mL, respectively (P<0.05). Median serum caspase-3 levels at baseline, 1 hour after anesthesia exposure, and 1-hour after cessation of anesthesia were 0.0028, 0.0682, and 0.0044 ng/mL, respectively (P<0.05)., Conclusions: Propofol, isoflurane, sevoflurane, or desflurane have similar effects on CSF and serum caspase-3. The reduction of intraoperative CSF caspase-3 levels suggests a possible role for general anesthesia in neuroresuscitation by slowing the neuronal apoptotic pathway., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Autism spectrum disorder (ASD) is classified as a neurodevelopmental disorder characterized by reduced social communication as well as repetitive behaviors. Many studies have proved that defective synapses in ASD influence how neurons in the brain connect and communicate with each other. Synaptopathies arise from alterations that affecting the integrity and/or functionality of synapses and can contribute to synaptic pathologies. This study investigated the GABA levels in plasma being an inhibitory neurotransmitter, caspase 3 and 9 as pro-apoptotic proteins in 20 ASD children and 20 neurotypical controls using the ELISA technique. Analysis of receiver-operating characteristic (ROC) of the data that was obtained to evaluate the diagnostic value of the aforementioned evaluated biomarkers. Pearson's correlations and multiple regressions between the measured variables were also done. While GABA level was reduced in ASD patients, levels of caspases 3 and 9 were significantly higher when compared to neurotypical control participants. ROC and predictiveness curves showed that caspases 3, caspases 9, and GABA might be utilized as predictive markers in autism diagnosis. The present study indicates that the presence of GABAergic dysfunction promotes apoptosis in Egyptian ASD children. The obtained GABA synaptopathies and their connection with apoptosis can both relate to neuronal excitation, and imbalance of the inhibition system, which can be used as reliable predictive biomarkers for ASD.

Sepsis is a dysregulated host response to infection related to devastating outcomes. Recently, interest has been shifted towards apoptotic and antiapoptotic pathobiology. Apoptosis is executed through the activation of caspases regulated by a number of antiapoptotic proteins, such as survivin. The survivin and caspases' responses to sepsis have not yet been elucidated. This is a multicenter prospective observational study concerning patients with sepsis (n = 107) compared to patients with traumatic systemic inflammatory response syndrome (SIRS) (n = 75) and to healthy controls (n = 89). The expression of survivin was quantified through real-time quantitative polymerase chain reaction for the different survivin splice variants (wild type-WT, ΔEx3, 2B, 3B) in peripheral blood leukocytes. The apoptotic or antiapoptotic tendency was specified by measuring survivin-WT, caspase-3, and -9 serum protein concentrations through enzyme-linked immunosorbent assay. The survivin-WT, -2B, -ΔΕx3 mRNA, survivin protein, and caspases showed an escalated increase in SIRS and sepsis, whereas survivin-3B was repressed in sepsis (p < 0.05). Survivin correlated with IL-8 and caspase-9 (p < 0.01). For discriminating sepsis, caspase-9 achieved the best receiver operating characteristic curve (AUROC) of 0.95. In predicting mortality, caspase-9 and survivin protein achieved an AUROC of 0.70. In conclusion, specific apoptotic and antiapoptotic pathways might represent attractive targets for future research in sepsis.

The development of drug resistance remains the major obstacle to clinical efficacy of cancer chemotherapy. Consequently, finding new therapeutic options for cancerous patients is an urgent need. Sixty newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients were recruited from Clinical Oncology Department, Faculty of Medicine, Menoufia University, Egypt prospectively randomized to three groups (n = 20 for each group). Group one (control group) received R-CHOP standard chemotherapy {Rituximab, Cyclophosphamide, Hydroxyldaunorubicin (Doxorubicin)®, Vincristine (oncovin)®, prednisolone in the first five days of cycle}, group two received lansoprazole (LAN) 60 mg p.o. bid for only one week before starting each of cycle + R-CHOP and group three received famotidine (FAM) 40 mg p.o. once daily one week before cycle and continues daily through the cycle + R-CHOP for six cycles. Blood samples were obtained for biochemical analysis of transforming growth factor-β (TGF-β), Basic fibroblast growth factor (bFGF), interleukin-9 (IL-9), nuclear factor-kappa B (NF-κB) and Caspase 3 before and after six cycles of therapy. The obtained data showed that LAN and FAM resulted in significant decrease in (LDH, TGF-β, bFGF and IL-9, respectively) and significant increase in (Caspase-3). In addition, LAN produced a significant elevation in the response rate compared to the control group or the FAM group. Both LAN and FAM as adjuvant therapy represents a promising anticancer strategy in DLBCL by modulation of malignancy homeostasis mechanisms and boosting chemotherapy antitumor effects without further toxicity. In addition, LAN has a synergetic effect in improving the response rate.Trial registration Clinical Trial.gov Identifier: NCT0364707.

In this study, changes in the blood tissue of rainbow trout ( Oncorhynchus mykiss, Walbaum, 1792 ) caused by Fipronil (FP) insecticide were investigated using different biomarkers (Hematology parameters, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), malondialdehyde (MDA), paraoxonase (PON), arylesterase (ARE), myeleperoxidase (MPO), micronucleus (MN), 8-hydroxy-2-deoxyguanosine (8-OHdG)) level and caspase-3 activity. Statistically significant alterations in hematology parameters occurred with FP effect. In blood tissue, dose-dependent inhibition was determined in SOD-CAT-GPX-PON and ARE enzyme activities, but MDA and MPO were induced statistically significant. The results of MN assay were compared with the control group and it was obtained that genotoxicity of different dose groups was similar. The level of 8-OHdG and the activity and caspase-3 examined in blood tissue was increased depending on the dose. It was determined with different biomarkers that this insecticide caused physiological stress changes in the tissues examined.

An inadequate platelet response to aspirin (ASA) has been identified in some patients under chronic ASA treatment. The aim of this study was to analyze if ASA-sensitive and ASA-resistant platelets have differences in their apoptotic capability. Clinically stable ischemic coronary patients who had been taking ASA (100 mg/d) for at least 9 months before inclusion were divided into ASA-resistant (n = 11) and ASA-sensitive (n = 13) groups as defined by the PFA-100 test. Platelets from ASA-sensitive patients showed higher expression of the proapoptotic proteins Bak and Bax than those from ASA-resistant patients, although only Bak protein remained different when the results were adjusted by age. In resting platelets, neither caspase-3 activity nor cytosolic cytochrome C levels were different between both experimental groups. Stimulation of platelets with calcium ionophore (10 nmol/L, A23187) increased caspase-3 activity (1.91-fold higher; P < 0.05) and cytosolic cytochrome C levels (1.84-fold higher; P < 0.05) to a higher degree in ASA-sensitive than in ASA-resistant platelets. In conclusion, ASA-sensitive platelets seem to be better prepared to undergo apoptosis during robust platelet activation.

The overexpression of inducible nitric oxide synthase (iNOS) induces cell apoptosis through various signal transduction pathways and aggravates lung injury. Caspase‑3 is an important protein in the apoptotic pathway and its activation can exacerbate apoptosis. Simvastatin, a hydroxymethyl glutaryl‑A reductase inhibitor, protects against smoke inhalation injury by inhibiting the synthesis and release of inflammatory factors and decreasing cell apoptosis. Following the establishment of an animal model of smoke inhalation injury, lung tissue and serum were collected at different time points and the protein and mRNA expression of iNOS and caspase‑3 in lung tissue by immunochemistry, western blot and reverse transcription‑quantitative polymerase chain reaction, the malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in lung tissue and serum were analyzed using thiobarbituric acid method and the WST‑1 method. The results were statistically analyzed. The lung tissues of the rats in the saline group and the low‑, middle‑ and high‑dose groups exhibited clear edema and hemorrhage, and had significantly higher pathological scores at the various time points compared with the rats in the control group (P<0.05). Furthermore, lung tissue and serum samples obtained from these four groups had significantly higher mRNA and protein expression levels of iNOS and caspase‑3 (P<0.05), significantly lower SOD activity and higher MDA content (P<0.05). Compared with the saline group, the low‑, middle‑ and high‑dose groups had significantly lower pathological scores (P<0.05), significantly lower mRNA and protein expression levels of iNOS, caspase‑3 and MDA content in lung tissues (P<0.05) and significantly higher SOD activity in lung tissues and serum. The middle‑ and high‑dose groups had significantly lower pathological scores (P<0.05), significantly decreased iNOS and caspase‑3 mRNA and protein expression in lung tissues, significantly higher SOD activity in lung tissues and serum and a significantly lower MDA content (P<0.05) compared with the low‑dose group. With the exception of SOD activity in lung tissues at 24 and 72 h and MDA content in serum at 48 h, no significant differences were observed between the middle‑ and high‑dose groups. The present study demonstrated that there was an association between the therapeutic effect and dosage of simvastatin within a definitive range. In rats with smoke inhalation injury, simvastatin inhibited iNOS and caspase‑3 expression in lung tissues and mitigated oxidative stress, thereby exerting a protective effect. In addition, the effect and dose were associated within a definitive range.

Background: Platelet apoptosis is considered as one of the important factors involved in platelet storage lesion (PSL) and affect the quality of platelets during storage. The beneficial effect of L-carnitine (LC) on platelet apoptosis during platelet concentrates (PCs) storage has not been fully investigated. The aim of this study was to evaluate the effects of LC on platelets of PC regarding their apoptosis markers during storage., Methods: Ten PCs from healthy donors were investigated in this study. PCs were prepared by platelet rich plasma (PRP) method and stored at 22±2°C with gentle agitation during storage. The effects of LC (15mM) on the platelet apoptosis were assessed by analyzing different indicative presence or absence of LC. Sampling was performed to evaluate apoptosis markers during platelet storage., Results: The results indicated significantly higher mitochondrial membrane potential for LC-treated platelets than the untreated on the days 2 and 5 of storage (P day2 =0.001, P day5 =0.001). Phosphatidylserine (PS) exposure significantly increased on the untreated compared with LC-treated platelets on the second and third days of storage (P day2 =0.014, P day3 =0.012). Also, active caspase 3 was lower in the LC- treated platelets than the control group on the day 5 of storage (P day5 =0.004). Cytosolic cytochrome C was so significantly lower in LC-treated compared to the untreated platelets during storage time (P day2 =0.002, P day3 =0.001, Pday5=0.001)., Conclusion: The results of this study indicate that the use of LC as an additive solution in platelets may be useful to reduce PSL by decreasing platelet apoptosis via mitochondrial pathway and increase platelet quality during storage., (Copyright © 2020 Société française de transfusion sanguine (SFTS). Published by Elsevier Masson SAS. All rights reserved.)

Background:  Implantable cardiovascular therapeutic devices, while hemodynamically effective, remain limited by thrombosis. A driver of device-associated thrombosis is shear-mediated platelet activation (SMPA). Underlying mechanisms of SMPA, as well as useful biomarkers able to detect and discriminate mechanical versus biochemical platelet activation, are poorly defined. We hypothesized that SMPA induces a differing pattern of biomarkers compared with biochemical agonists., Methods:  Gel-filtered human platelets were subjected to mechanical activation via either uniform constant or dynamic shear; or to biochemical activation by adenosine diphosphate (ADP), thrombin receptor-activating peptide 6 (TRAP-6), thrombin, collagen, epinephrine, or arachidonic acid. Markers of platelet activation (P-selectin, integrin αIIbβ3 activation) and apoptosis (mitochondrial membrane potential, caspase 3 activation, and phosphatidylserine externalization [PSE]) were examined using flow cytometry. Platelet procoagulant activity was detected by chromogenic assay measuring thrombin generation. Contribution of platelet calcium flux in SMPA was tested employing calcium chelators, ethylenediaminetetraacetic acid (EDTA), and BAPTA-AM., Results:  Platelet exposure to continuous shear stress, but not biochemical agonists, resulted in a dramatic increase of PSE and procoagulant activity, while no integrin αIIbβ3 activation occurred, and P-selectin levels remained barely elevated. SMPA was associated with dissipation of mitochondrial membrane potential, but no caspase 3 activation was observed. Shear-mediated PSE was significantly decreased by chelation of extracellular calcium with EDTA, while intracellular calcium depletion with BAPTA-AM had no significant effect. In contrast, biochemical agonists ADP, TRAP-6, arachidonic acid, and thrombin were potent inducers of αIIbβ3 activation and/or P-selectin exposure. This differing pattern of biomarkers seen for SMPA for continuous uniform shear was replicated in platelets exposed to dynamic shear stress via circulation through a ventricular assist device-propelled circulatory loop., Conclusion:  Elevated shear stress, but not biochemical agonists, induces a differing pattern of platelet biomarkers-with enhanced PSE and thrombin generation on the platelet surface. This differential biomarker phenotype of SMPA offers the potential for early detection and discrimination from that mediated by biochemical agonists., Competing Interests: Y.R.-M., D.B., and M.J.S. have a patent PCT/US2019/037528 pending to University of Arizona.J. I. reports personal fees from Platelet BioGenesis, outside the submitted work., (Georg Thieme Verlag KG Stuttgart · New York.)

Aim: Disturbed placentation results in pregnancy complications like preeclampsia. Placental development is influenced by apoptosis during trophoblast differentiation and proliferation. Increased oxidative stress upregulates placental apoptosis. We have earlier reported increased oxidative stress, lower omega-3 fatty acids and vitamin E levels in women with preeclampsia. Current study examines effect of maternal omega-3 fatty acids and vitamin E supplementation on apoptotic markers across gestation in a rat model of preeclampsia., Main Methods: Pregnant Wistar rats were randomly assigned to control; early onset preeclampsia (EOP); late onset preeclampsia (LOP); early onset preeclampsia + omega-3 fatty acid + vitamin E supplementation (EOP + O + E) and late onset preeclampsia + omega-3 fatty acid + vitamin E supplementation (LOP + O + E) groups. Animals (Control, EOP, EOP + O + E) were sacrificed at d14 and d20 of gestation while animals (LOP, LOP + O + E) were sacrificed at d20 to collect blood and placentae. Protein and mRNA levels of apoptotic markers were analyzed by ELISA and RT-PCR respectively., Key Findings: Protein levels of proapoptotic markers like Bcl-2 associated X-protein (BAX) (p < 0.05), caspase-8 and 3 (p < 0.01 for both) and malondialdehyde (p < 0.01) were higher only in the EOP group as compared to control. However, the antiapoptotic marker, B cell lymphoma 2 (Bcl-2) protein levels were lower in both the subtypes of preeclampsia (p < 0.01 for both)., Significance: Our findings suggest that supplementation was beneficial in reducing the caspase-8 and 3 in early onset preeclampsia but did not normalize BAX and Bcl-2 levels. This has implications for reducing placental apoptosis in preeclampsia., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Anti-neoplastic agents are widely used in the treatment of cancer and some non-neoplastic diseases. These drugs have been proved to be carcinogens, teratogens, and mutagens. Concern exists regarding the possible dangers of the staff handling anti-cancer drugs. The long-term exposure of nurses to anti-neoplastic drugs is still a controversial issue. The purpose of this study was to monitor cellular toxicity parameters and gene expression in nurses who work in chemotherapy wards and compare them to nurses who work in other wards., Methods: To analyze the apoptosis-related genes overexpression and cytotoxicity effects, peripheral blood lymphocytes obtained from oncology nurses and the control group., The Results: Significant alterations in four analyzed apoptosis-related genes were observed in oncology nurses. In most individual samples being excavated, Bcl-2 overexpression is superior to that of Bax. Prominent P53 and Hif-1α up-regulation were observed in oncology nurses. Moreover, all cytotoxicity parameters (cell viability, ROS formation, MMP collapse, Lysosomal membrane damage, Lipid peroxidation, Caspase 3 activity and Apoptosis phenotype) in exposed oncology nurses were significantly (p < 0.001) higher than those of unexposed control nurses. Up-regulation of three analyzed apoptosis-related genes were observed in nurses occupationally exposed to anti-cancer drugs., Conclusion: Our data show that oxidative stress and mitochondrial toxicity induced by anti-neoplastic drugs lead to overexpression of apoptosis-related genes in oncology nurses.

Purpose: Circulating caspase-3 levels at 24 h of ischemic stroke were found to be associated with poorer functional neurological outcome in a previous study. The aim of this study was to determine whether there is an association between serum caspase-3 levels and early mortality in patients with malignant middle cerebral artery infarction (MMCAI)., Methods: We included patients with MMCAI defined as computer tomography showing ischemic changes in more than 50% of the middle cerebral artery territory and Glasgow Coma Scale ≤ 8. Serum caspase-3 levels at days 1, 4, and 8 of MMCAI were determined., Results: Non-surviving MMCAI (n = 34) showed higher serum caspase-3 levels at days 1 (p < 0.001), 4 (p = 0.001), and 8 (p = 0.01) than surviving patients (n = 34). We found that the area under the curve of serum caspase-3 levels for prediction of mortality at 30 days was 88% (95% CI = 78-95%; p < 0.001). Multiple logistic regression showed that serum caspase-3 levels were associated with 30-day mortality (OR = 51.25; 95% CI = 8.30-316.31; p < 0.001)., Conclusions: The novel and more important findings of our study were that high serum caspase-3 levels were associated with mortality in MMCAI patients.

Objective: Behçet's syndrome (BS) is a chronic, multisystemic and inflammatory syndrome. In our study, we aimed to compare the initiator, effector and inflammatory caspases and pannexin channel protein, which is thought to have an activity in inflammation, in the inflammatory process of BS, with healthy subjects, to investigate their level in patients and their relationship with the clinical findings., Method: Forty-six patients who were under follow-up for BS in the Sivas Cumhuriyet University Medical Faculty Department of Internal Diseases, Rheumatology Unit, between January 2017 and June 2017 and 44 healthy controls (HC) who did not have any rheumatic, systemic or metabolic diseases, were enrolled in this study., Results: The mean serum pannexin-1 level was 6.36 (4.21-527.2) pg/mL in the BS group and 255.8 (5.38-2000) pg/mL in the HC group. Serum pannexin-1 levels were statistically significantly lower in the BS group (P < 0.0001). The measured mean serum caspase-3 level was 12.04 (11.25-43.69) pg/mL in the group with BS and 12.1 (11.19-484.3) pg/mL in the HC group (P = 0.143), mean serum caspase-9 level was 22 (5.14-29.33) pg/mL in the BS group and 22.01 (11.23-850) pg/mL in the HC group (P = 0.593), mean serum caspase-14 level was 6 (5.2-8.21) pg/mL in the BS group and 6.15 (5.7-353) pg/mL in the HC group (P = 0.053)., Conclusion: Comparison of serum caspase-3, caspase-9 and caspase-14 levels in subjects with BS and in the HC group did not reveal any statistically significant differences. On the other hand, serum pannexin-1 levels were statistically significantly lower in the BS group., (© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background : Higher liver caspase-3 activity has been found in patients with different liver diseases. However, there is no published data about circulating caspase-3 levels in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT). Therefore, our objective in this study was to determine whether an association between circulating caspase-3 levels in HCC patients prior to LT and one-year mortality after LT exists. Methods : In this observational and retrospective study, we included HCC patients who underwent LT. We measured serum levels of caspase-3 (as the main executor of apoptosis) and caspase-cleaved cytokeratin (CCCK)-18 (to estimate apoptosis degree) before LT. Results : One-year surviving LT patients (n = 129) showed lower serum levels of caspase-3 (p = 0.004) and CCCK-18 (p = 0.001) than non-surviving LT patients (n = 16). Logistic regression analysis showed that serum caspase-3 levels prior to LT were associated with one-year after LT mortality (Odds Ratio = 2.612; 95% CI = 1.519-4.493; p = 0.001). We found a positive association between serum levels of caspase-3 and CCCK-18 (rho = 0.26; p = 0.002). Conclusions : Our study is the first one reporting data of circulating caspase-3 levels prior to LT for HCC, and an association between high serum caspase-3 levels previously to LT and survival at first year after LT.

Chemotherapy leads to a loss of fertility and reproductive endocrine function, thereby increasing the risk of premature ovarian failure (POF). Studies have suggested that the transplantation of mesenchymal stem cells could inhibit apoptosis in ovarian granulosa cells and improve follicular development. In the present study, the effects of human umbilical cord mesenchymal stem cell (UCMSC) transplantation on ovarian function after ovarian damage caused by chemotherapy and the mechanism underlying these effects were investigated. POF model rats were obtained by the intraperitoneal injection of cyclophosphamide, and cultured UCMSCs were transplanted by tail vein injection. Serum estrogen, follicle-stimulating hormone, gonadotropin releasing hormone, and anti-Mullerian hormone levels were detected by ELISA. Folliculogenesis was evaluated by histopathological examination. The expression levels of nerve growth factor (NGF), high affinity nerve growth factor receptor (TrkA), follicle-stimulating hormone receptor (FSHR), and caspase-3 were evaluated by western blotting and RT-qPCR. The natural reproductive capacity was assessed by pregnant rate and numbers of embryos. The results indicated that UCMSC transplantation recovered disturbed hormone secretion and folliculogenesis in POF rats. NGF and TrkA levels increased, while FSHR and caspase-3 decreased. The pregnancy rate of POF rats was improved. Therefore, UCMSCs could reduce ovarian failure due to premature senescence caused by chemotherapy, and the NGF/TrkA signaling pathway was involved in the amelioration of POF.

Objective: To study the protective mechanism of ibuprofen (Ib) in myocardial ischemia-reperfusion (I/R) injury in rats, and to analyze its regulatory effect on the phosphatidylinositol 3-hydroxy kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway., Materials and Methods: The rat model of myocardial I/R injury was established via ligation of the left main coronary artery (LCA) for 30 min and then reperfusion for 120 min. A total of 36 Sprague-Dawley (SD) rats were randomly divided into sham group (S group, n=12), model group (I/R group, n=12) and Ib group (n=12). The levels of serum creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in each group were detected. The rats were executed, the heart was isolated and the area of myocardial infarction was determined via 2,3,5-triphenyltetrazolium chloride (TTC) staining. The expression levels of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1 (HIF-1) and apoptosis-related proteins in myocardial tissues in each group were detected via Western blotting. Moreover, the content of inflammatory factors in myocardial tissues in each group was detected using the enzyme-linked immunosorbent assay (ELISA) kit. The expression levels of related proteins in the PI3K/Akt/mTOR signaling pathway in myocardial tissues were further analyzed., Results: Compared with those in S group, the levels of CK-MB and LDH were significantly increased (p<0.01), the area of myocardial infarction was significantly increased (p<0.01), the VEGF, HIF-1 and Cleaved caspase-3 protein levels in myocardial tissues were increased (p<0.01), while Bcl-2/Bax declined (p<0.01), the content of interleukin-1 (IL-1), IL-6 and tumor necrosis factor-α (TNF-α) in myocardial tissues was increased (p<0.01), while the content of IL-10 declined (p<0.01), and the expression levels of PI3K, p-Akt and p-mTOR proteins in myocardial tissues were significantly decreased (p<0.01) in I/R group. Compared with those in I/R group, the levels of CK-MB and LDH were significantly decreased (p<0.01), the area of myocardial infarction was significantly decreased (p<0.01), the VEGF, HIF-1 and Cleaved caspase-3 protein levels in myocardial tissues were decreased (p<0.01), while Bcl-2/Bax was increased (p<0.01), the content of IL-1, IL-6 and TNF-α in myocardial tissues declined (p<0.01), while the content of IL-10 was significantly increased (p<0.01), and the expression levels of PI3K, p-Akt and p-mTOR proteins in myocardial tissues were significantly increased (p<0.01) in Ib group., Conclusions: Ib can activate the PI3K/Akt/mTOR signaling pathway, reduce the release of inflammatory factors and apoptosis, and alleviate the myocardial I/R injury in myocardial cells in rats.

Evidence is accumulating that cardiac apoptosis occurs and contributes to myocyte cell death during myocardial ischemia. Cardioplegia, defined as the temporary cessation of cardiac activity during cardiac surgery, is a clinically controlled condition with myocardial ischemia and reperfusion. Our goal was to determine whether the apoptotic biomarker caspase-3 p17 is elevated in the coronary sinus (CS) during cardioplegia and if any elevations were reflected in the peripheral venous (PV) blood. Levels of the necrotic biomarker cardiac troponin I (cTnI) and the inflammatory marker caspase-1 p20 were also quantified in CS and PV. Blood was drawn before and at the end of cardioplegia in PV and CS and levels of p20, p17, and cTnI were measured. cTnI, p20, and p17 PV levels were significantly elevated compared with the control population before and at the end of cardioplegia. PV levels of all 3 markers increased after cardioplegia. CS levels were higher than PV levels for all 3 markers at both time points. Our data are consistent with the occurrence of cardiac apoptosis and inflammation during cardioplegia, in addition to necrosis. The heart-derived markers contributed to the peripheral levels and suggest that measurement of PV biomarker concentrations can be used to gauge cardiac preservation., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

BACKGROUND Cardiac remote ischemic conditioning (RIC) is a noninvasive cardioprotective method in ischemia-reperfusion injury and acute myocardial infarction (AMI). The aims of this study were to investigate the effects of RIC in a rat model of AMI. MATERIAL AND METHODS Adult male Sprague-Dawley rats included the AMI group that underwent ligation of the left anterior descending (LAD) coronary artery (n=24), the RIC group that consisted the AMI rat model treated with RIC once daily in the left hind limb until days 1, 7 and 14 (n=24), and the sham group (n=24). Myocardial infarct size was measured by routine histology with triphenyltetrazolium chloride (TTC) and Masson's trichrome histochemical staining for myocardial necrosis and fibrosis, respectively. Serum levels of Bcl-2, Bax, caspase-3, and inducible nitric oxide synthase (iNOS) were measured by enzyme-linked immunosorbent assay (ELISA). The apoptosis index was detected using the TUNEL assay. Spectrophotometry of the myocardium was used to identify mitochondrial complexes and myocardial ATP. RESULTS The RIC group showed improved cardiac hemodynamics, reduced the size of the myocardial infarction, upregulated expression of Bcl-2, and down-regulation of the levels of Bax, caspase-3, and iNOS, and reduced cardiac myocyte apoptosis and inhibited the opening of the mitochondrial permeability transition pore (MPTP). CONCLUSIONS In a rat model of AMI, RIC improved the hemodynamic index, reduce the levels of apoptosis and myocardial injury, and improved mitochondrial function.

Caspases play a central role in apoptosis, inflammation, and fibrosis. They produce hemodynamically active, proinflammatory microparticles that cause intrahepatic inflammation, vasoconstriction, and extrahepatic splanchnic vasodilation. Emricasan is a pan-caspase inhibitor that lowers portal hypertension (PH) and improves survival in murine models of cirrhosis. This exploratory study assessed whether emricasan lowers PH in patients with compensated cirrhosis. This multicenter, open-label study enrolled 23 subjects with compensated cirrhosis and PH (hepatic vein pressure gradient [HVPG] >5 mm Hg). Emricasan 25 mg twice daily was given for 28 days. HVPG measurements were standardized and performed before and after emricasan. A single expert read all HVPG tracings. Median age was 59 (range 49-80); 70% were male. Cirrhosis etiologies were nonalcoholic steatohepatitis and hepatitis C virus. Subjects were Child class A (87%) with a median Model for End-Stage Liver Disease score of 8 (range 6-15). Twelve had severe PH (HVPG ≥12 mm Hg). Overall, there was no significant change in HVPG after emricasan (mean [standard deviation, SD] -1.1 [4.57] mm Hg). HVPG decreased significantly (mean [SD] -3.7[4.05] mm Hg; P = 0.003) in those with severe PH: 4/12 had a ≥20% decrease, 8/12 had a ≥10% decrease, and 2/12 HVPG decreased below 12 mm Hg. There were no significant changes in blood pressure or heart rate. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) decreased significantly in the entire group and in those with severe PH. Serum cleaved cytokeratin 18 and caspase-3/7 decreased significantly. Emricasan was well tolerated. One subject discontinued for nonserious adverse events. Conclusion: Emricasan administered for 28 days decreased HVPG in patients with compensated cirrhosis and severe PH; an effect upon portal venous inflow is likely, and concomitant decreases in AST/ALT suggest an intrahepatic anti-inflammatory effect., (© 2018 The Authors. Hepatology published by Wiley Periodicals, Inc. on behalf of American Association for the Study of Liver Diseases.)

The manganese-dependent superoxide dismutase (MnSOD) Ala16Val single nucleotide polymorphism (SNP) has shown to be associated to risk factors of vascular diseases. Brain-Derived Neurotrophic Factor (BDNF) plays an essential role in the plasticity and neuronal regeneration of the brain after vascular injuries. However, little is known about interaction between MnSOD Ala16Val SNP on stroke, a frequent neurologic disease that involves various interacting pathways, such as vascular dysfunctions, inflammation, and neurotrophic factors. In this sense, the objective of this study was to investigate the relationship between MnSOD Ala16Val SNP with BDNF levels on stroke and also its influence on nitrosative stress, inflammatory, apoptotic, and DNA damage parameters. For this, 88 subjects were investigated, 44 subjects poststroke and 44 healthy controls. Questionnaires were applied to clinical characteristics and after laboratorial exams were collected. We analyzed levels of oxidative/nitrosative stress, inflammatory, apoptotic, and DNA damage markers. We showed a higher proportion of VV genotype in poststroke as compared to healthy subjects. Nitrite/nitrate, Tumor Necrosis Factor-α, Caspase 3 (CASP 3) and 8 (CASP 8) activation, Acethylcholinesterase (AChE), and Picogreen levels were higher in VV poststroke group, as well as BDNF and ACh levels were lower in VV and AV poststroke. We may suggest that V allele carries a worse outcome profile after stroke, relating to nitrosative stress, inflammatory, and apoptotic response. These events associated to a BDNF reduction, probably, contribute to the appearance or reincidence of stroke., (Copyright © 2018. Published by Elsevier Inc.)

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.

Yaks (Bos grunniens) have special physiological structures that help them adapt to high-altitude environments. Survivin is actively studied in cancer tissues, but less in normal tissues. Therefore, the aim of the present study was to analysis the relationship between survivin expression and apoptosis rate in yaks. A partial gene sequence of survivin was cloned and characterized using bioinformatics. The expression of survivin was investigated using real-time quantitative PCR (RT-qPCR) and western blot (WB) analysis and localized using immunohistochemistry (IHC). The results revealed that in normal physiological organs, survivin is mainly expressed in cytoplasm and its expression was up-regulated with age. Its expression in heart and liver was higher than in other organs, such as spleen, lung, brain, kidney, and testis. It is noteworthy that the expression of survivin in spleen is differed from that in other organs. Therefore, we selected immune organs (lymph node, thymus and spleen) to investigate the relationship between survivin expression and apoptosis. Caspase-3 was used as a reference. Within the same age group, the expression of survivin was the highest in the spleen, but that of caspase-3 was the highest in the lymph node (P < 0.01). Furthermore, the IHC analysis revealed that survivin and caspase-3 are expressed in the same location (mainly in the cytoplasm, Hassall's corpuscles, the medulla of the lymph node, the red pulp and marginal zone of the spleen. More importantly, survivin expression was down-regulated with age in immune organs, and the opposite trend was observed for caspase-3 expression (P < 0.01). The results proved that the expression of survivin and caspase-3 is down- and up-regulated with age, respectively, suggesting that survivin and caspase-3 might coordinating and participating in slowing down the rate of apoptosis rate in immune organs of healthy yak., (Copyright © 2018. Published by Elsevier Inc.)

Objective To investigate the clinical application value of circulating miR-29a in diagnosis and prognosis monitoring in acute pancreatitis (AP) patients, and to preliminary explore the molecular pathology significance of high expression of miR-29a. Methods 30 cases of mild acute pancreatitis (MAP) patients (MAP group) and 30 cases of moderately serve acute pancreatitis (MSAP) or serve acute pancreatitis (SAP) patients ( M-SAP group) were randomly selected, and 30 cases of healthy adults were used as control group. The general clinical data of each group were compared, and miR-29a levels in peripheral blood were measured by real tome quantitative PCR, then the correlation between miR-29a levels and Ranson score or APACHEIIscore were analyzed. The clinical usefulness of miR-29a for AP patients was assessed by ROC curve analysis. AR42J cells were treated with deoxycholic acid (DCA) to establish AP cell model, the expression levels of miR-29a and caspase-3 were detected. AR42J cells were transfected by lentiviral vector contain miR-29a mimic or miR-29a AMO and measured of expression levels of miR-29a and caspase-3. Results In acute phase, the expression of circulating miR-20a was up-regulated in MAP and M-SAP group patients, and miR-20a levels of M-SAP group patients were higher than MAP group patients. In same group, miR-20a levels in acute phase were higher than recovery phase. Correlation analysis indicated the positive correlation between miR-20a levels and Ranson score or APACHEII score. ROC curve analysis indicated that the AUC of miR-29a for diagnosis MAP patients was 0.961 ( 95%CI: 0.921~ 1.002), cut-off value was 1.460. The AUC of miR-29a for diagnosis M-SAP patients was 0.972 ( 95%CI: 0.939 ~ 1.004), cut-off value was 1.340. The expression levels of miR-29a and caspase 3 were increased in AP cell model. Moreover, caspase 3 levels in AP cell model were increased than vector control after overexpression of miR-29a, and caspase-3 levels were reduced than vector control after suppressing of miR-29a expression. Conclusion Circulating miR-29a is high expression in MAP and M-SAP patients, and high expression of miR-29a may relate to pancreatic acinar cell apoptosis, and this biomarkers has high clinical value in AP diagnosis and prognosis monitoring.

Purpose: To investigate the apoptotic mechanisms in rabbits with blast-induced acute lung injury (ALI)., Methods: A total of 40 rabbits were randomly divided into a blank control group (A, n=10) and an experimental group (EXP, n=30). Explosion-induced chest-ALI models were prepared and sampled at different time points (4, 12, and 24h after modeling, T1-T3) to test the lung dry weight/wet weight ratio (W/D) and arterial oxygen pressure (PaO2), apoptosis of lung tissue by the TUNEL assay, and Caspase-3, Bax, and Bcl-2 levels by immunohistochemical analysis. Furthermore, lung tissue was sampled to observe pathological morphology by microscopy., Results: Under a light microscope, Group EXP exhibited obvious edema in the pulmonary interstitial substance and alveoli, a large number of red blood cells, inflammatory cells, and serous exudation in the alveolar cavity, as well as thickening of the pulmonary interstitial fluid. Compared to Group A, the W/D ratio was significantly increased in Group EXP (P<0.01), while PaO2 was significantly reduced (P<0.01). The apoptosis index was significantly increased (P<0.01), and caspase-3 and Bax/Bcl-2 levels were increased (P<0.01)., Conclusion: Apoptosis plays an important role in the occurrence and development of acute lung injury in rabbits by participating in lung injury and promoting the progression of ALI.

To investigate the role of S100B, oxidative stress and the apoptosis signaling pathways in the sevoflurane induced neuroprotective effect on stroke. The brain injury, molecular and cellular damage, and functional recovery were investigated upon ischemic brain injury followed by sevoflurane treatment. Longa rodent stroke scales was used to quantify neurological deficits. TTC staining was used to measure infarct volume of brain tissue. Absolute brain water content was measured by wet/dry weight method. The neuronal morphological change was assessed by H and E staining. The spatial learning and memory ability were measured by water maze test. Serum proteins including S100B, GSH-PX, SOD, Bcl-2, Bax, Caspase-3 were measured by ELISA. The level of NOS and NO in serum was determined by colorimetric method. Compared with control, the serum proteins including S100B, Bax, NO, Caspase-3, and NOS activity in cerebral infarction rats increased significantly while SOD, GSH-PX, and Bcl-2 decreased significantly. Diabetic mellitus complicated with cerebral infarction rats showed more dramatic increase for S100B, Bax, NO, Caspase-3, and NOS activity and dramatic decrease for SOD, GSH-PX, and Bcl-2. Interestingly, sevoflurane reduced the changes significantly. The S100B level positively correlated with brain damage, NO, Bax, caspase-3, and NOS activity but negatively correlated with SOD, Bax, and GSH-PX. Brain damage in sevoflurane groups decreased while behavior outcomes including Longa neurologic score, learning, and memory increased significantly. The neuroprotective effect of sevoflurane is associated with defense mechanisms against free radical-induced oxidative stress and inhibition of apoptosis. S100B protein correlated with oxidative stress and the apoptosis signaling pathways.

Peripheral nervous system neurotoxicity is the most problematic complication of cisplatin treatment. In this study, we have addressed the possible neuroprotective effect of canagliflozin on cisplatin-induced peripheral neurotoxicity in rats. Rats were randomly allocated into the following: control (vehicle) group, received hydhroxypropyl methyl cellulose; cisplatin group, injected cisplatin 2 mg/kg intraperitoneal, twice a week for 5 consecutive weeks; canagliflozin-cisplatin of received canagliflozin, 10 mg/kg/day by gavage and cisplatin in the same schedule like cisplatin group. Thermal nociception and rotarod performance were assessed. Malondialdehyde (MDA), reduced glutathione (GSH), tumor necrosis factor-α (TNF-α), and caspase 3 were determined in serum. Hematoxylin and eosin (H&E) and immunohistochemical stained sciatic nerve sections were examined. Cisplatin induced thermal hypoalgesia and decreased rotarod performance as well as GSH serum level while increased MDA, TNF-α, and caspase-3 serum levels with atrophy and fragmentation of the nerve fibers with decreased expression of myelin basic protein. Canagliflozin prevented thermal hypoalgesia and improved rotarod performance with increment in GSH serum level while decreased MDA, TNF-α, and caspase-3 levels as well as prevented fragmentation of the nerve fibers and enhanced myelin basic protein expression in relation to cisplatin group. Canagliflozin attenuates the neurotoxic effect of cisplatin through anti-inflammatory and anti-oxidant actions as well as inhibition of apoptosis.

Aim To investigate the lipid membranes of rat enterocytes in chronic carrageenan-induced gastroenterocolitis accompanied by the activation of apoptotic processes. Methods Steady-state fluorescence spectroscopy: a study by fluorescent probes - by ortho-hydroxy derivatives of 2,5-diaryl-1,3- oxazole. Activity of apoptosis signal-regulating kinase 1 and poly (ADP-ribose) polymerase in small intestinal homogenates, blood serum levels of matrix metalloproteinase-2 and caspase-3 and the level of DNA fragmentation in small intestinal homogenates were determined. Results Biochemical analysis revealed that an activation of apoptotic processes occurred in the intestinal epithelium of rats during chronic carrageenan-induced gastroenterocolitis. The fluorescence probes showed that activation of apoptotic processes in carrageenan-induced gastroenterocolitis was accompanied by changes in polar regions of rat enterocyte membranes, while no changes were revealed in more hydrophobic regions of the membranes. Conclusion The increase in hydration of membranes was attributed to the activation of the apoptosis of enterocytes. It has been shown that a fluorescent probe (2-(2'-hydroxyphenyl)-5-phenyl-1,3-oxazole) can be used for the detection of apoptosis of enterocytes., (Copyright© by the Medical Assotiation of Zenica-Doboj Canton.)

Objective: Melatonin has a protective role in adults with cardiovascular disease, but the effects of melatonin in children with cardiac dysfunction are not well understood. This study was designed to explore the variations in melatonin, myeloperoxidase, and caspase-3 levels in children suffering from heart failure., Methods: Seventy-two pediatric patients with heart failure and twelve healthy children were enrolled in this study. A modified Ross scoring system was used to evaluate clinical cardiac function. Patients with a score of >2 points were included in the study and were divided into three groups according to severity of heart failure: mild (score: 3-6), moderate (score: 7-9), and severe (score: 10-12). Echocardiographic parameters, laboratory data, and serum levels of melatonin, myeloperoxidase, and caspase-3 were measured and analyzed in all patients., Results: Compared with patients with mild and moderate heart failure, patients in the severe heart failure group had significantly decreased left ventricular ejection fraction (p<0.001), and significantly increased serum melatonin levels (p=0.013) and myeloperoxidase levels (p<0.001). Serum melatonin levels were positively correlated with serum caspase-3 levels (p<0.001). The optimal cutoff values of serum melatonin levels for the diagnosis of severe heart failure and primary cardiomyopathy in pediatric patients with heart failure were 54.14pg/mL and 32.88pg/mL, respectively., Conclusions: Serum melatonin and myeloperoxidase levels were increased in children with severe heart failure. It is likely that increasing melatonin levels may act as a compensatory mechanism in pediatric children with heart failure., (Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Elevated blood glucose and insulin resistance are triggering factors for non-alcoholic steatohepatitis (NASH). We investigated the effects of the Sodium Glucose co-Transporter 2 (SGLT2) inhibitor canagliflozin on NASH development in rats with type 2 diabetes mellitus as well as the possible underlying mechanisms and for the first time the effect of canagliflozin on the hepatic zinc-α2-glycoprotein (ZAG) levels. Rats were treated with nicotinamide and streptozotocin to reduce the insulin secretory capacity then fed high fat diet for 8 weeks. The diabetic high fat diet rats were divided into three groups; untreated group, canagliflozin 10 mg/kg treated group and canagliflozin 20 mg/kg treated group during this period. The elevated blood glucose and glycated haemoglobin (HbA1c) levels in the diabetic high fat diet rats were significantly reduced by canagliflozin. Moreover, the diabetic high fat diet induced NASH development as evidenced by liver weight gain, hepatic lipid accumulation and low hepatic ZAG expression as well as increased serum alanine aminotransferase; all these changes were reversed in rats treated with canagliflozin. Additionally, canagliflozin succeeded to upregulate the hepatic ZAG levels in both normal and diabetic high fat fed rats, lower the serum and hepatic inflammatory cytokines levels as well as lower the serum caspase-3 levels and enhanced hepatic Bcl-2 expression. Also, canagliflozin attenuated hepatic oxidative stress and elevated the antioxidant enzymes activity as well as the total antioxidant capacity. All these effects of canagliflozin were dose dependant., Conclusion: SGLT2 inhibitor-canagliflozin- has beneficial effects in treatment of NASH associated with diabetes mellitus., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: The study was processed to investigate the effect of astaxanthin (AST; 3,3-dihydroxybeta, beta-carotene-4,4-dione) on the acute kidney injury induced by iohexol and the relationship with SIRT1/FOXO3a signal pathway., Methods: Thirty male Sprague Dawley rats were randomly divided into five groups as follows: control group (CON; olive oil only), contrast media group, astaxanthin control group (100 mg/kg), low astaxanthin dose group (LAG, 50 mg/kg) and high astaxanthin dose group (HAG, 100 mg/kg). As followed, serum creatinine (SCr), blood urea nitrogen (BUN), the oxidative stress markers and apoptosis-related proteins were detected. Human proximal tubular epithelial cells (HK-2) were cultured in DMEM/F12 medium in vitro and then randomly divided into appropriate experimental groups: normal group (N), dimethyl sulfoxide (DMSO), iohexol group (I), iohexol + (1.0, 10.0 μmol/L) astaxanthin group (I + LAST; I + HAST), iohexol + SIRT1 inhibitors (nicotinamide) group (NA) and iohexol + si-RNA FOXO3a group (si-RNA FOXO3a); when cultured for 24 h, cell proliferation ability was tested by cell counting kit (CCK-8), reactive oxygen species (ROS) were detected by flow cytometry and the expression of SIRT1 and FOXO3a were observed using western blot., Results: At the end of the experiment, the levels of SCr, BUN and malondialdehyde (MDA) were all increased in the CM group. The LAG and HAG reduce superoxide anion (SOD) activity, catalase (CAT) activity, glutathione peroxidase (GPx) activity and glutathione (GSH) content, as well as SCr and BUN level. Moreover, apoptosis-associated proteins, caspase 3 p17, bax and bcl-2 were upregulated. In HK-2 cells, after adding iohexol, proliferation and intracellular ROS levels were significantly increased. Using astaxanthin in advance after the intervention, the result is opposite. SIRTl inhibitors NA can reduce the expression of SIRTl and decrease the expression of FOXO3a protein. Si-RNA FOXO3a reduces the expression of FOXO3a but had no significant effect on the expression of SIRT1., Conclusions: Our study demonstrates that the intervention of astaxanthin could attenuate the oxidative stress and apoptosis in contrast-induced acute kidney injury (CI-AKI), and the SIRT1/FOXO3a pathway participates in the contrast-induced apoptosis of HK-2 cells. Finally, astaxanthin reduces CI-AKI by suppression of apoptosis, which may be through inhibition of SIRT1/FOXO3a pathways.

The aims of this study were to investigate the interplay between autophagy and apoptosis and to investigate the association between both of autophagy and apoptosis and vitamin D and its receptor in hepatitis C virus (HCV) viral infection and its implication in the progression into hepatocellular carcinoma (HCC).A cross-sectional study where serum levels of microtubule-associated protein 1A/1B-light chain 3 (LC3); marker of autophagy, caspase-3; marker of apoptosis, vitamin D3 and vitamin D receptor (VDR) were measured in healthy subjects as well as HCV and HCV-HCC patients using enzyme-linked immunosorbent assay technique.Collectively, the liver profile revealed hepatic dysfunctions in HCV patients with or without HCC. A significant reduction in the serum concentration levels LC3 and caspase-3 were observed referring to the down regulation of autophagy and host-mediated apoptosis in HCV patients with or without HCC. Deficiency of vitamin D and decreased levels of its receptor were observed in HCV and HCV-HCC patients.The perturbation in vitamin D/VDR axis, which modulates both of autophagy and apoptosis in HCV infection, may point out to its involvement and implication in the pathogenesis of HCV infection and the development of HCV-related HCC. Therefore, supplementation with vitamin D may not be the only solution to restore the vital biological functions of vitamin D but VDR-targeted therapy may be of great importance in this respect.

Caspase-3 is the main executor of the apoptotic process. Higher serum caspase-3 concentrations in non-survivor compared to survivor septic patients have been found. The objectives of this work (with the increase of sample size to 308 patients, and the determination of serum caspase-3 concentrations also on days 4 and 8 of diagnosis of severe sepsis) were to know whether an association between serum caspase-3 concentrationss during the first week, degree of apoptosis, sepsis severity, and sepsis mortality exists. We collected serum samples of 308 patients with severe sepsis from eight intensive care units on days 1, 4 and 8 to measure concentrations of caspase-3 and caspase-cleaved cytokeratin (CCCK)-18 (to assess degree of apoptosis). End point was 30-day mortality. We found higher serum concentrations of caspase-3 and CCCK-18 in non-survivors compared to survivors on days 1 (p < 0.001), 4 (p < 0.001), and 8 (p < 0.001). We found an association between serum caspase-3 concentrations on days 1, 4 and 8 of severe sepsis diagnosis and serum CCCK-18 concentrations (p < 0.001), SOFA (p < 0.001), serum acid lactic concentrations (p < 0.001), and 30-day sepsis mortality (p < 0.001). The new findings of this work were that an association between serum caspase-3 concentrations during the first week, apoptosis degree, sepsis severity, and sepsis mortality exists.

Background: Topiramate (TPM) decreases cytokine release and generation of reactive oxygen species (ROS). Cytokine and endothelin-1 (ET-1) secretion and ROS formation play an important role in ischemia-reperfusion (I/R) injury. We aimed to evaluate whether TPM prevents damage occurring in lung tissue during I/R., Materials and Methods: A total of 27 Wistar albino rats were divided into three groups of nine. To the I/R group, two hours of ischemia via infrarenal abdominal aorta cross-ligation and then two hours of reperfusion process were applied. TPM (100 mg/kg/day) orally for seven days was administered in the TPM treatment group. After the last dose of TPM treatment, respectively, two hours of ischemia and two hours of reperfusion were applied in this group., Results: Tumor necrosis factor-alpha (TNF-α) (p < 0.05), malondialdehyde (MDA) (p < 0.05), myeloperoxidase (MPO) (p < 0.05) and ET-1 (p < 0.05) levels of TPM treatment group's lung tissue were significantly lower than for the I/R group. Caspase-3 and histopathological damage were rather lower than that of the I/R group., Conclusions: During I/R, lung damage occurs due to excessive TNF-α and ET-1 release and ROS generation. TPM could well reduce development of lung damage by decreasing cytokine and ET-1 release and levels of ROS produced.

The aim of the present study was to investigate the cardioprotective effects of anisodamine against myocardial ischemia/reperfusion (I/R) injury and the molecular mechanisms involved. The present results demonstrated that anisodamine attenuated myocardial infarct sizes, decreased the levels of creatine kinase and lactate dehydrogenase, whereas it increased the left ventricular (LV) systolic pressure, the LV end‑diastolic pressure, and the LV pressure maximum rising and falling rates in a myocardial I/R rat model. In addition, anisodamine was revealed to suppress oxidative stress, inflammatory factor production and myocardial cell apoptosis, as demonstrated by the downregulation of caspase‑3 and apoptosis regulator BAX protein expression. The production of reactive oxygen species was decreased and the protein expression of inducible nitric oxide synthase (iNOS) was downregulated, whereas the expression of endothelial NOS was enhanced. In addition, the activity of nicotinamide‑adenine dinucleotide phosphate oxidase (Nox) was suppressed and the expression of Nox4 was downregulated in rats with myocardial I/R injury. In conclusion, the results of the present study suggested that anisodamine exerted a cardioprotective effect against myocardial I/R injury in rats, through the inhibition of oxidative stress, the suppression of inflammatory processes and the inhibition of myocardial cell apoptosis.

Background/aims: To identify the role of serum caspase 3, Annexin A2 (ANXA2), and Soluble Fas Ligand (sFasL) levels in the prediction of endometriosis severity., Methods: The study was performed on 90 women who were candidates for laparoscopic surgery due to endometrioma or any other benign ovarian cysts detected by ultrasound examination, pelvic pain, or infertility. The control group comprised 29  patients. The second group comprised 29 patients with stage I-II endometriosis and the third group comprised 30 patients with stage III-IV endometriosis., Results: Significant differences were detected between the control and stage III-IV endometriosis groups and between stage I-II and stage III-IV endometriosis groups in terms of caspase-3 levels (both, p < 0.001), ANXA2 levels (p = 0.007 and p = 0.002), and sFasL levels (p = 0.022 and p = 0.044). After receiver operating characteristic analysis, the area under curve was 93% (95% CI 57-82) at 10.7 ng/mL cut-off level for caspase-3 with 90% sensitivity and 87% specificity., Conclusion: Serum caspase-3 level may be a reliable predictor of endometriosis severity., (© 2018 S. Karger AG, Basel.)

Background: Cardiorenal syndrome type 1 (CRS type 1) is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Its pathophysiology is complex and not completely understood. In this study, we examined the role of apoptosis and the caspase pathways involved., Material and Methods: We enrolled 40 acute heart failure (AHF) patients, 11 of whom developed AKI characterizing CRS type 1. We exposed the human cell line U937 to plasma from the CRS type 1 and AHF groups and then we evaluated apoptotic activity by annexin-V evaluation, determination of caspase-3, -8 and -9 levels, and BAX, BAD, and FAS gene expression., Results: We observed significant upregulation of apoptosis in monocytes exposed to CRS type 1 plasma compared to AHF, with increased levels of caspase-3 (p < 0.01), caspase-9 (p < 0.01), and caspase-8 (p < 0.03) showing activation of both intrinsic and extrinsic pathways. Furthermore, monocytes exposed to CRS type 1 plasma had increased gene expression of BAX and BAD (intrinsic pathways) (p = 0.010 for both). Furthermore, strong significant correlations between the caspase-9 levels and BAD and BAX gene expression were observed (Spearman ρ = - 0.76, p = 0.011, and ρ = - 0.72, p = 0.011)., Conclusion: CRS type 1 induces dual apoptotic pathway activation in monocytes; the two pathways converged on caspase-3. Many factors may induce activation of both intrinsic and extrinsic apoptotic pathways in CRS type 1 patients, such as upregulation of proinflammatory cytokines and hypoxia/ischemia. Further investigations are necessary to corroborate the present findings, and to better understand the pathophysiological mechanism and consequent therapeutic and prognostic implications for CRS type 1., (© 2018 S. Karger AG, Basel.)

Background: One of the important risk factors for dementia is chronic cerebral hypoperfusion (CCH) especially in patients with cerebrovascular disease., Objectives: In the present study, using rat model of bilateral common carotid artery occlusion, the possible protective effects of ethyl pyruvate (EP) have been explored in terms of memory impairment, oxidative stress, and levels of caspase-3, Na-K ATPase, and IL- 1β., Methods: Rats were treated with EP (50 mg/kg, i.p) for 4 weeks. Cognitive function was evaluated by Morris Water Maze (MWM). Both levels of caspase-3 and Na-K ATPase in tissue, IL-1β in plasma were measured by ELISA method. Status of oxidative stress in brain was assessed by the measurements of the tissue malondialdehyde (MDA) and reduced glutathione (GSH) contents.  RESULTS: Results showed that CCH caused a striking impairment of spatial working memory, accompanied with increased levels of MDA and IL-1β as well as caspase 3 level. The treatment with EP, however, significantly improved the memory impairment. Moreover, the treatment also provided beneficial effects on the disturbances of caspase 3, IL-1β and MDA., Conclusion: This study strongly imply that the EP administration can alleviate the memory impairment observed due to CCH. The protection provided by EP may result from inhibition of inflammatory response, apoptotic processes and oxidative stress (Fig. 3, Ref. 58).

Background: To investigate the effects of obesity on CD47, phosphatidylserine (PS) exposure, and Caspase-8 and Caspase-3 activities in erythrocytes., Methods: The study included 25 morbidly obese patients and 20 healthy people as the control group. We evaluated CD47 expression on the red blood cell (RBC) membrane surface and eryptosis markers such as PS externalization and caspase activity using flow cytometric analyses., Results: CD47 expression on the RBC surface was significantly lower in obese patients than in the control group (P = 0.000001). We did not find significant differences in the Caspase-3 and Caspase-8 activities between the obese and nonobese control groups. Additionally, we did not find differences in PS exposure on erythrocyte membranes. The fibrinogen levels were higher in the obese group than they were in the control group (P = 0.00002). Correlations between CD47 expression and body mass index (r = -0.65; P = 0.0004), waist circumference (r = -0.54; P = 0.0052), and fibrinogen (r = 0.57; P = 0.0024) were found. Univariate analyses revealed that body mass index, waist circumference, hip circumference, and fibrinogen levels were potential predictors of CD47 expression. Multivariate analyses found that fibrinogen levels (β = 0.4708; P = 0.045) independently predicted CD47 expression., Conclusions: The study demonstrated that CD47 expression is decreased on the surface of RBCs in obese subjects. These changes in CD47 expression on the RBC surface may be an adaptive response to hyperfibrinogenemia associated with obesity. © 2015 International Clinical Cytometry Society., (© 2015 International Clinical Cytometry Society.)

Objective: To investigate the potential of the baseline gene expression in the whole blood of disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis (RA) patients for predicting the response to methotrexate (MTX) treatment., Methods: Twenty-six control subjects and 40 RA patients were examined. Clinical, immunological and radiographic parameters were assessed before and after 24 months of follow-up. The gene expressions in the whole blood were measured using real-time reverse transcription polymerase chain reaction. The protein concentrations in peripheral blood mononuclear cells were quantified using enzyme-linked immunosorbent assay. Receiver operating characteristic curve analyses were used to suggest thresholds that were associated with the prediction of the response., Results: Decreases in the disease activity at the end of the study were accompanied by significant increases in joint space narrowing score (JSN). Positive correlations between the expressions of the Unc-51-like kinase 1 (ULK1) and matrix metalloproteinase 9 (MMP-9) genes with the level of C-reactive protein and MMP-9 expression with Disease Activity Score of 28 joints (DAS28) and swollen joint count were noted at baseline. The baseline tumor necrosis factor (TNF)α gene expression was positively correlated with JSN at the end of the follow-up, whereas p21, caspase 3, and runt-related transcription factor (RUNX)2 were correlated with the ΔDAS28 values., Conclusions: Our results suggest that the expressions of MMP-9 and ULK1 might be associated with disease activity. Increased baseline gene expressions of RUNX2, p21 and caspase 3 in the peripheral blood might predict better responses to MTX therapy., (© 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background and Purpose: Stroke diagnosis could be challenging in the acute phase. We aimed to develop a blood-based diagnostic tool to differentiate between real strokes and stroke mimics and between ischemic and hemorrhagic strokes in the hyperacute phase., Methods: The Stroke-Chip was a prospective, observational, multicenter study, conducted at 6 Stroke Centers in Catalonia. Consecutive patients with suspected stroke were enrolled within the first 6 hours after symptom onset, and blood samples were drawn immediately after admission. A 21-biomarker panel selected among previous results and from the literature was measured by immunoassays. Outcomes were differentiation between real strokes and stroke mimics and between ischemic and hemorrhagic strokes. Predictive models were developed by combining biomarkers and clinical variables in logistic regression models. Accuracy was evaluated with receiver operating characteristic curves., Results: From August 2012 to December 2013, 1308 patients were included (71.9% ischemic, 14.8% stroke mimics, and 13.3% hemorrhagic). For stroke versus stroke mimics comparison, no biomarker resulted included in the logistic regression model, but it was only integrated by clinical variables, with a predictive accuracy of 80.8%. For ischemic versus hemorrhagic strokes comparison, NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) >4.9 (odds ratio, 2.40; 95% confidence interval, 1.55-3.71; P <0.0001) and endostatin >4.7 (odds ratio, 2.02; 95% confidence interval, 1.19-3.45; P =0.010), together with age, sex, blood pressure, stroke severity, atrial fibrillation, and hypertension, were included in the model. Predictive accuracy was 80.6%., Conclusions: The studied biomarkers were not sufficient for an accurate differential diagnosis of stroke in the hyperacute setting. Additional discovery of new biomarkers and improvement on laboratory techniques seem necessary for achieving a molecular diagnosis of stroke., (© 2017 American Heart Association, Inc.)

To explore the effect of leech on proliferation and apoptosis of vascular smooth muscle cells(VSMCs) in early atherosclerosis rats via p38MAPK signaling pathway and investigate its possible mechanism. Biochemical analyzer was used to examine the regulation of leech on levels of triglycerides(TG), total cholesterol(TC), low-density lipoprotein(LDL-C), and high-density lipoprotein(HDL-C) in blood lipid of rats. The expression of transforming growth factor-beta 1(TGF-β1) in serum was detected by ELISA. Immunological histological chemistry (IHC) was taken to measure the expression levels of proliferating cell nucleus antigen(PCNA) and cell apoptosis proteinase-3(Caspase-3), while the protein expression levels of MKK3, p38 and C-myc were detected by Western blot. In addition, hematoxylin and eosin(HE) staining was used to observe the morphological change of thoracic aortas. The results showed that leech decreased the levels of TC, LDL-C obviously and increased HDL-C, suppressed the expression levels of TGF-β1 and PCNA, up-regulated Caspase-3, down-regulated the expression levels of MKK3, p38, and C-myc protein. HE staining indicated that it could inhibit intimal thickening and reduce plaque formation. The above results indicated that leech may affect the protein expression of the p38MAPK signaling pathway to inhibit proliferation and promote the apoptosis of VSMCs via reducing blood lipid levels and suppressing TGF-β1, aiming at inhibiting intimal thickening and reducing plaque formation, tand then slowing down the process of early atherosclerosis., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Background: Caspase-3 is a potential marker of apoptosis. We investigated whether serum caspase-3 concentrations were increased and its association with severity and prognosis after intracerebral hemorrhage (ICH)., Methods: This prospective clinical study recruited 112 ICH patients and 112 healthy individuals. Serum was assayed for caspase-3 using enzyme-linked immunosorbent assay. Stroke severity was quantified by National Institute of Health Stroke Scale (NIHSS) and hematoma volume. Six-month outcome was measured by modified Rankin Scale. Analyses were performed using univariate and multivariate analyses., Results: Patients had significantly higher serum caspase-3 concentrations than controls. Capase-3 concentrations correlated with NIHSS score and hematoma volume. Serum caspase-3 emerged as an independent predictor for 6-month mortality and bad prognosis (modified Rankin scale score>2). Based on receiver operating characteristic curve, caspase-3 concentrations showed similar prognostic value when compared with NIHSS score and hematoma volume., Conclusion: Serum caspase-3 concentrations are increased in ICH patients as well as correlate with clinical severity and prognosis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The cardio-protective effects of zinc oxide nanoparticles (Zn NPs) against diabetes-induced cardiopathy were evaluated and compared with zinc sulfate (ZnSO 4 ). A total of 120 Wistar rats were randomly categorized as healthy and diabetic groups. Then, the 2 groups were classified in 5 subgroups. The animals received oral supplementations containing different Zn NP (ie, doses of 1, 3, and 10mg/kg) and ZnSO 4 (30mg/kg) concentrations over 8 weeks. Blood and cardiac tissue samples were collected in the different time intervals and subjected to biochemical and histopathological analysis. Zn NPs showed dual effects, as its middle dose played protective role and recovered cardiac damages evidenced by significant reduction of serum cholesterol, HDL-cholesterol, lipoprotein (a), atherogenic index, TNF-α, cardiac MDA, B-type natriuretic peptide and caspase-3 activity. Apoptosis indices and histopathological features also were improved. However, the highest dose was found to be toxic and resulted in aggravation of the injuries. Another interesting finding is the ability of the higher doses of Zn-NPs (3 and 10mg/kg) to elevate cardiac zinc levels above the normal range in healthy animal. ZnSO 4 also helped to recuperation of the damages, but the middle dose of Zn NPs was more efficient as compared to ZnSO 4 . Conclusively, Zn NPs have the potential for Zn delivery in diabetic patients., (Copyright © 2017 Elsevier GmbH. All rights reserved.)