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The study is to investigate the effect of Euphorbia angustifolia lactone B (Jolkinolide B, JB) on the proliferation and apoptosis of A549 cells. The proliferation of A549 cells was detected by tetramethyl azothiolide. Activity changes of intracellular caspase-3, 8, 9 were determined by spectrophotometry. The content of cytochrome C (Cyt C) protein and the expression quantity of Bcl-2, Bax, p-ERK1/2, and p-Akt proteins were detected by Western blot and the apoptosis rates were detected by flow cytometry. JB significantly inhibited cell proliferation in a time-dose manner. With increase in JB concentrations, the expression level of Bax protein greatly increased, and the expression of caspase-3 and caspase-9 significantly increased with significant difference (P<0.01). Besides, the peak value of mitochondrial membrane potential decreased, while the number of cells distributed in the depolarized region increased, which was different from that in the control (P<0.05). Moreover, the expression levels of p-ERK1/2 and p-Akt in A549 cells gradually decreased with extending exposure duration. Moreover, 20 μ mol/L LY294002 (an PI3K inhibitor) + 120μg/mL JB and 10μmol/L PD98059 (an ERK inhibitor) +120μg/mL JB also increased apoptosis rates of A549 cells. JB could induced cell apoptosis through promoting endogenous mitochondrial signal transduction pathway and inhibiting PI3K/ERK pathway.

This study was aimed to investigate the protective effects of Lepidium draba L. (L. draba) extract on oxymetholone (OM)‐induced testicular injury in rat. Six groups of n = 5 adult male rats were used as; 1: control, 2: OM (5 mg/kg OM orally), 3, 4 and 5: L. draba extract (100, 200 and 400 mg kg−1 day−1) +OM (5 mg kg−1 day−1 OM) and 6:400 mg/kg/d L. draba extract for 30 days. Serum testosterone (T), follicle‐stimulating hormone (FSH) and luteinising hormone (LH), inflammatory cytokines (IL‐6, IL‐10, TNF‐α, IL‐1β), oxidative stress (OS) indicators [superoxide dismutase, catalase, glutathione peroxidase and nitric oxide (NO)], apoptotic related genes (Bcl‐2, p53, caspase‐3 (c3) and Bax) were investigated. OM significantly increased the serum levels of T, proinflammatory cytokines and pro‐apoptotic genes expression. Also, it decreased LH and FSH, sperm viability, count and motility. L. draba extract especially could markedly normalise the serum levels of LH and FSH, and T, restore serum antioxidant enzymes and suppressed the pro‐inflammatory cytokines. Also, germ cells apoptosis was inhibited against via downregulating the p53, c3, Bax and upregulating Bcl‐2. It concluded that L. draba extract could protect the function and structure of testis against OM‐induced testicular toxicity via its antioxidant and anti‐inflammatory properties. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the protective effects of Lepidium draba L. extract on cyclophosphamide (CP)‐induced oxidative damages to testes in rats using sex hormones, antioxidant properties, inflammatory, and apoptotic pathways. Six groups of male Wistar rats (n = 6/group) received distilled water (NC), CP (100 mg kg–1 day–1/intraperitoneal), CP with L. draba extract [100 (LDCP 100), 200 (LDCP 200), and 400 (LDCP 400) mg/kg/day/orally] and also only L. draba extract [400 (LD400) mg/kg/day/orally] in 35 days. On day 36 of the study, sperm parameters, serum levels of sex hormones, antioxidant enzyme activity, nitric oxide levels, and inflammatory cytokines and also testicular tissue (ferric reducing antioxidant power and thiobarbituric acid reactive substances levels and expression of ROS‐dependent pro/anti‐apoptotic pathways) were evaluated. In L. draba‐treated groups, especially doses of 200 and 400, in addition to improving sperm parameters and sex hormones (Increased levels of all three hormones luteinizing hormone, follicle‐stimulating hormone, and testosterone), serum antioxidant (catalase, superoxide dismutase, and glutathione peroxidase activity increased and nitric oxide levels decreased), and anti‐inflammatory properties (levels of IL‐6, TNF‐α, and IL‐1β decreased and MIF and TGF‐β increased) also showed modification. By strengthening the anti‐apoptotic pathway of Keap1/Nrf2/HO1 and inhibiting the apoptotic pathway of Bax/Bcl2/p53/caspase‐3, L. draba maintains the structure and function of testicular tissue so that eventually p53‐positive testicular cells are reduced and Bcl‐2‐positive cells increased. L. draba can help to maintain sexual potency and fertility in patients undergoing chemotherapy by controlling their apoptotic, anti‐inflammatory, and antioxidant pathways. Practical applications: Lepidium draba have considerable antioxidant properties and can help to maintain sexual potency and fertility in patients undergoing chemotherapy by controlling their apoptotic, anti‐inflammatory, and antioxidant pathways. The present results are useful to find a suitable supplement for improving the sexual performance of patients treated with chemotherapy drugs. [ABSTRACT FROM AUTHOR]

Objective: Tumor cells could acquire drug resistance through cell autophagy. This study aimed to explore the role of SNHG16 in sorafenib‐resistant HCC cells and its mechanism with miR‐23b‐3p. Methods: The sorafenib‐resistant Hep3B cell model was established. The SNHG16 and miR‐23b‐3p gene expressions were determined in normal HCC and sorafenib‐resistant HCC tissues. Detection of the expression of SNHG16 and miR‐23b‐3p and its respective correlation with survival rate were performed. Target genes to SNHG16 and miR‐23b‐3p were predicted, and verified by dual‐fluorescent reporter assay. The effects of SNHG16 and miR‐23b‐3p on SNHG16, miR‐23b‐3p, EGR1 expression, viability, apoptosis as well as LC3II/LC3 expression in Hep3B and Hep3B/So cells were detected by qRT‐PCR, CCK‐8, flow cytometry, and western blot. In in vivo studies, the NOD/SCID mice model was established to explore the effects of Hep3B and Hep3B/So cells with inhibited SNHG16 or miR‐23b‐3p on tumor size, EGR1 expression, and autophagy. Results: High SNHG16 expression in HCC‐resistant tissues and low miR‐23b‐3p expression in all HCC tissues were detected, and the two were negatively correlated. Low SNHG16 and high miR‐23b‐3p were related to a high survival rate of HCC patients. Moreover, SNHG16 overexpression promoted Hep3B/So cell viability and autophagy, suppressed apoptosis by inhibiting miR‐23b‐3p expression through up‐regulating EGR1, however, the effect of si‐SNHG16 was opposite. In in vivo studies, miR‐23b‐3p inhibitor suppressed the high sorafenib sensitivity in Hep3B/So cells caused by SNHG16 silencing through promoting viability, autophagy, and suppressing apoptosis. Conclusion: SNHG16 promotes Hep3B/So cell viability, autophagy, and inhibits apoptosis to maintain its resistance to sorafenib through regulating the expression of miR‐23b‐3p via sponging EGR1. [ABSTRACT FROM AUTHOR]

CD44, a cell‐surface glycoprotein, functions as a receptor for hyaluronic acid. Our research group has previously shown that CD44 is a biomarker for the CD44hi cells (tumor‐initiating cells; TICs) in murine salivary gland tumors. However, little is known concerning the biological roles of CD44 in the tumorigenesis of pleomorphic adenoma. The present study is aimed to investigate the effects of CD44 on the proliferation, invasive capability, and apoptosis of TICs in vitro, as well as the tumorigenicity of TICs in vivo. The results demonstrated that knockdown of CD44 attenuated the malignant phenotype of TICs. Furthermore, in vivo xenograft studies indicated that CD44 knockdown inhibited tumorigenesis of pleomorphic adenoma. In addition, neither the CD44low cells nor the CD44‐modified CD44low cells developed neo‐tumors, which indicated that overexpression of CD44 did not enable the CD44low cells to be transformed into TICs. Taken together, these data demonstrate that CD44 not only acts as a biomarker, but also functions as a key player in the tumor‐initiating capacity of TICs. These results shed light on the pathogenesis of salivary gland tumors and provide a potential therapeutic target for treating pleomorphic adenoma. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related death due to the failure of traditional therapies. In the present study, we attempted to construct a lncRNA-miRNA-mRNA network which may modulate PDAC cell proliferation and Gemcitabine-induced cell apoptosis starting from CDK14, a new member of the CDK family and an oncogene in many cancers. Based on TCGA data, a significant positive correlation was observed between lncRNA MSC-AS1 and CDK14. Moreover, MSC-AS1 expression was upregulated in PDAC tissues. Higher MSC-AS1 expression was correlated with poorer prognosis in patients with PDAC. MSC-AS1 knockdown in Panc-1 and BxPC-3 cells significantly inhibited the cell proliferation. Moreover, miR-29b-3p, which has been reported to act as a tumor suppressor, was predicted to bind to both MSC-AS1 and CDK14. Contrary to MSC-AS1, higher miR-29b-3p expression was correlated to better prognosis in patients with PDAC. In both PDAC cell lines, miR-29b-3p negatively regulated MSC-AS1 and CDK14. As confirmed using luciferase reporter gene and RIP assays, MSC-AS1 served as a ceRNA for miR-29b-3p to counteract miR-29b-mediated CDK14 repression. MSC-AS1 knockdown inhibited CDK14 protein levels and PDAC proliferation and enhanced gemcitabine-induced cell death and apoptosis while miR-29b-3p inhibition exerted an opposing effect; the effect of MSC-AS1 knockdown was partially attenuated by miR-29b-3p inhibition. Taken together, we demonstrated that MSC-AS1/miR-29b-3p axis modulates the cell proliferation and GEM-induced cell apoptosis in PDAC cell lines through CDK14. We provided a novel experimental basis for PDAC treatment from the perspective of lncRNA-miRNA-mRNA network. [ABSTRACT FROM AUTHOR]

Background/Aims: The increasing prevalence of ionizing radiation exposure has inevitably raised public concern over the potential detrimental effects of ionizing radiation on male reproductive system function. The detection of drug candidates to prevent reproductive system from damage caused by ionizing radiation is urgent. We aimed to investigate the protective role of taurine on the injury of mouse spermatocyte-derived cells (GC-2) subjected to ionizing radiation. Methods: mouse spermatocytes (GC-2 cells) were exposed to ionizing radiation with or without treatment of Taurine. The effect of ionizing radiation and Taurine treatment on GC-2 cells were evaluated by cell viability assay (CCK8), cell cycle and apoptosis. The relative protein abundance change was determined by Western blotting. The siRNA was used to explore whether Nrf2 signaling was involved in the cytoprotection of Taurine. Results: Taurine significantly inhibited the decrease of cell viability, percentage of apoptotic cells and cell cycle arrest induced by ionizing radiation. Western blot analysis showed that taurine significantly limited the ionizing radiation-induced down-regulation of CyclinB1 and CDK1, and suppressed activation of Fas/FasL system pathway. In addition, taurine treatment significantly increased the expression of Nrf2 and HO-1 in GC-2 cells exposed to ionizing radiation, two components in antioxidant pathway. The above cytoprotection of Taurine was blocked by siNrf2. Conclusion: Our results demonstrate that taurine has the potential to effectively protect GC-2 cells from ionizing radiation-triggered damage via upregulation of Nrf2/HO-1 signaling. [ABSTRACT FROM AUTHOR]

Introduction: Observing the effects of high-volume hemofiltration (HVHF) treatment on the monocytes apoptosis, antigen presentation, and secretion function, this study investigated the mechanism of HVHF effect on immunity homeostasis in multiple organ dysfunction syndrome (MODS) in an animal model.Materials and Methods: Lipopolysaccharides were administered in 12 Beagle dogs in order to induce MODS. Six dogs were randomly assigned to receive HVHF treatment for 12 hours (HVHF group) and the rest did not receive any treatment (the MODS group). The expression of DLA-DR, apoptosis, and cytokine levels were measured at 7 time points: normal condition (T1), after operation (T2), and zero, 3, 6, 9, and 12 hours after endotoxin injection (T3 to T7, respectively).Results: Apoptosis of CD14+ mononuclear cell increased in early and late stages gradually in the MODS group and began to decline gradually after the HVHF treatment. There was a significant difference between the two groups at time points T2 to T7 (P < .01). After HVHF, the impaired expression of dog leukocyte antigen-DR showed an improvement trend in the HVHF group, which was significant better at T5 and T7 than that in the MODS group (P < .05). Interleukin-4 secretion increased significantly with HVHF and was significantly higher at time points T4 to T7 as compared with the MODS group (P < .01).  Conclusions. High-volume hemofiltration can alleviate the mononuclear cell apoptosis, improve antigen-presenting function and secretion function, inhibit the release of inflammatory factors, and maintain immune homeostasis, and consequently alleviate symptoms of MODS effectively. [ABSTRACT FROM AUTHOR]

Aims: p21Waf1/Cip1 is a cyclin-dependent kinase inhibitor that is pivotal in arresting cellular growth in terminal cell differentiation and apoptosis. Thus, the existence of natural variants of p21 Waf1/Cip1 could be linked to specific cancer. The purpose of this report was to identify a novel tri-allelic insertion/deletion (INDEL) polymorphism (rs4135235) involving a poly-T sequence in the promoter region of p21 Waf1/Cip1 gene and to explore its role in gastric cancer (GC). Method: A total of unrelated 676 subjects (376 GC patients; 300 cancer-free controls) were enrolled in the study, and genomic DNA was obtained from each subject for genotyping. PCR-directed sequencing technique was used to detect the genotypes of the polymorphism. TA cloning was used to confirm the existence of three alleles. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression analysis. Results: Six genotypes (9T/9T, 10T/10T, 11T/11T, 9T/10T, 10T/11T, and 9T/11T) and three alleles (9Ts, 10Ts, and 11Ts) were identified among all study subjects. GC cases were different from the control group with over-representation of 9T/11T heterozygotes (19.7% vs. 12.3%) and under-representation of 10T/10T homozygotes (18.4% vs. 20.7%). Compared with those carrying 10T/10T, individuals with 9T/11T increased the susceptibility for GC (OR=1.797, 95%CI=1.065-3.031). Conclusion: Our findings confirmed the existence of a tri-allelic polymorphism in the promoter of p21 Waf1/Cip1. It has also shown the heterozygous genotype 9T/11T to be a potential risk factor for GC in the Chinese population. [ABSTRACT FROM AUTHOR]