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Myocardial ischemia-reperfusion injury (MIRI) is a phenomenon that reperfusion leads to irreversible damage to the myocardium and increases mortality in acute myocardial infarction (AMI) patients. There is no effective drug to treat MIRI. Tubeimoside I (TBM) is a triterpenoid saponin purified from Chinese traditional medicine tubeimu. In this study, 4 mg/kg TBM was given to mice intraperitoneally at 15 min after ischemia. And TBM treatment improved postischemic cardiac function, decreased infarct size, diminished lactate dehydrogenase release, ameliorated oxidative stress, and reduced apoptotic index. Notably, ischemia-reperfusion induced a significant decrease in cardiac SIRT3 expression and activity, while TBM treatment upregulated SIRT3's expression and activity. However, the cardioprotective effects of TBM were largely abolished by a SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP). This suggests that SIRT3 plays an essential role in TBM's cardioprotective effects. In vitro , TBM also protected H9c2 cells against simulated ischemia/reperfusion (SIR) injury by attenuating oxidative stress and apoptosis, and siSIRT3 diminished its protective effects. Taken together, our results demonstrate for the first time that TBM protects against MIRI through SIRT3-dependent regulation of oxidative stress and apoptosis. TBM might be a potential drug candidate for MIRI treatment., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Dingyi Lv et al.)

The biological function of miRNA (miR)-424-5p in glioma has not been clarified. This study was to explore the roles of miR-424-5p/Bifunctional apoptosis regulator (BFAR) axis in glioma. Ninety-six pairs of human glioma tissues and their adjacent non-cancer tissues were collected. The levels of BFAR and miR-424-5p were detected by quantitative polymerase chain reaction (qPCR) in glioma tissues and cell lines. Moreover, the biological roles of miR-424-5p and BFAR in glioma cells were assessed. We found a miR-424-5p binding site in the 3'UTR of BFAR by using TargetScan 7.2 online database. The miR-424-5p level was dramatically decreased in glioma tissues and cell lines, and the BFAR expression was significantly increased. The BFAR expression was negatively related to the miR-424-5p level in glioma tissues. Compared to patients with high miR-424-5p levels in glioma tissues, patients with low miR-424-5p levels had significantly lower survival rate (χ 2  = 13.728 and P < 0.001). Compared to patients with high BFAR levels in glioma tissues, patients with low BFAR levels had significantly higher survival rate (χ 2  = 5.516 and P = 0.027). Furthermore, up-regulation of miR-424-5p obviously restrained glioma cells proliferation and invasion, and promoted apoptosis. Besides, knockdown of BFAR also could markedly inhibit the proliferation and invasion, and promote apoptosis. Finally, overexpression of BFAR in glioma cells partially reversed the inhibited effects of miR-424-5p mimic. Knockdown of miR-424-5p restrained glioma cell apoptosis and promoted invasion and proliferation via regulation of BFAR.

Programmed cell death (PCD) refers to the way in which cells die depending on specific genes encoding signals or activities. Apoptosis, autophagy, and pyroptosis are all mechanisms of PCD. Among these mechanisms, pyroptosis is mediated by the gasdermin family, accompanied by inflammatory and immune responses. The relationship between pyroptosis and cancer is complex, and the effects of pyroptosis on cancer vary in different tissues and genetic backgrounds. On one hand, pyroptosis can inhibit the occurrence and development of tumors; on the other hand, as a type of proinflammatory death, pyroptosis can form a suitable microenvironment for tumor cell growth and thus promote tumor growth. In addition, the induction of tumor pyroptosis is also considered a potential cancer treatment strategy. Studies have shown that DFNA5 (nonsyndromic hearing impairment protein 5)/GSDME (Gasdermin-E) mRNA methylation results in lower expression levels of DFNA5/GSDME in most tumor cells than in normal cells, making it difficult to activate the pyroptosis in most tumor cells. During the treatment of malignant tumors, appropriate chemotherapeutic drugs can be selected according to the expression levels of DFNA5/GSDME, which can be upregulated in tumor cells, thereby increasing the sensitivity to chemotherapeutic drugs and reducing drug resistance. Therefore, induced pyroptosis may play a predominant role in the treatment of cancer. Here, we review the latest research on the anti- and protumor effects of pyroptosis and its potential applications in cancer treatment.

Larvae of the fox tapeworm, Echinococcus multilocularis, cause alveolar echinococcosis, which is considered to be the most lethal helminthic infection in humans. Since it develops in host organs, the parasite must have evolved a stress defense system to cope with various genotoxic and cellular stresses that may cause DNA damage and genomic instability. Tumor suppressor p53, well known as the "guardian of the genome", plays a vital role in response to many types of stress and damage. In the present study, we describe the characterisation of Emp53 from E. multilocularis and demonstrate that it is a structural and functional homologue of mammalian tumor suppressor p53. We show that Emp53 binds specifically to oligonucleotides containing conventional p53 binding sites, indicating that it exhibits a function as a DNA binding transcription factor. Inhibition of Emp53 function can suppress UV irradiation-induced apoptosis in the E. multilocularis metacestode, indicating an important role of Emp53 in the induction of apoptosis following DNA damage. We also reveal that Emp53 plays important roles in resistance to oxidative stress and regulation of oxidative stress-induced apoptosis. Our results suggest that, similar to its human counterpart, Emp53 plays a central role in the network of DNA damage responses and apoptosis in E. multilocularis. These results may help in exploring stress defense mechanisms of parasitic helminths and may provide useful information for the development of new interventions and therapeutic drugs for the control of alveolar echinococcosis., (Copyright © 2015 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.)

Experimental studies have demonstrated that lanthanides could impair cognitive functions of children and animals, but very little is known about the hippocampal apoptosis and its molecular mechanism. The study investigated the signal pathway of hippocampal apoptosis induced by intragastric administration of CeCl(3) for 60 consecutive days. It showed that cerium had been significantly accumulated in the mouse hippocampus, and CeCl(3) caused hippocampal apoptosis and impairment of spatial recognition memory of mice. CeCl(3) effectively activated caspase-3 and -9, inhibited Bcl-2, and increased the levels of Bax and cytochrome c, promoted accumulation of reactive oxygen species in the mouse hippocampus. It implied that CeCl(3)-induced apoptosis in the mouse hippocampus could be triggered via mitochondrion-mediated pathway. Our findings suggest the need for great caution to handle the lanthanides for workers and consumers., (2011 Wiley Periodicals, Inc)

Cerium (Ce) was shown to cause various toxic effects both in rats and mice; however, the molecular mechanism by which Ce exert theirs toxicity is still understood. In this report, the impairment of liver DNA conformation and liver apoptosis of mice caused by CeCl(3) was studied in vivo using inductively coupled plasma-mass spectrometry, various spectral methods, gel electrophoresis, and transmission electron micrograph. We found that the coefficients of liver to body weight of the mice treated with CeCl(3) were significantly increased. Ce(3+) could be significantly accumulated in the liver, and it insert itself into DNA base pairs and/or bind to DNA nucleotide, and alter the conformation of DNA. Furthermore, the evaluation by gel electrophoresis and transmission electron micrograph showed that higher dose of Ce(3+) could cause DNA cleavage and hepatocyte apoptosis in mice. Therefore, our study aroused the attention of Ce application and exposure effects especially on human liver for long-term and low-dose treatment.

Previous studies demonstrate that the exposure to titanium dioxide nanoparticles (TiO(2) NPs) damages the central nervous system of mice; however, very little is known about the effects of TiO(2) NPs on hippocampal apoptosis or its molecular mechanism. The present study investigated the molecular mechanism associated with hippocampal apoptosis in mice induced by intragastric administration of TiO(2) NPs for consecutive 60 days. Our findings indicate that TiO(2) NPs accumulate in the mouse hippocampus, and this accumulation, in turn, led to hippocampal apoptosis and impairment in spatial recognition memory in mice. In addition, TiO(2) NPs significantly activated caspase-3 and -9, inhibited Bcl-2, and promoted the levels of Bax and cytochrome c. Furthermore, TiO(2) NPs induced accumulation of reactive oxygen species in the mouse hippocampus. These findings suggest that TiO(2) NP-induced apoptosis in the mouse hippocampus may result from an intrinsic pathway, and workers and consumers should take great caution when handling nanomaterials., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Purpose: Candida albicans is one of the main opportunistic pathogen for human , the aim of this study is to investigate the phenomena of apoptosis in oral Candida albicans induced by acetic acid., Methods: The Candida albicans of clinical strains were induced to apoptosis by using a weak acid acetic acid.The apoptosis was detected by flow cytometry and TEM. The data were processed for Chi-square test using SPSS11.5 software package., Results: Oral Candida albicans had classic apoptosis when induced by proper concentration of acetic acid, and different concentrations of acetic acid had variable ability of inducing apoptosis of Candida albicans., Conclusions: Apoptosis can be detected in clinical strains of Candida albicans, the mechanism of apoptosis needs further research for the purpose of developing new antifungal drugs. Supported by National Natural Science Foundation of China(Grant No.30400498) and 2007 National College Student Innovative Planning Project.

Cell death is an important physiological and pathological phenomenon in multicellular animals and occurs widely in various body's systems. In recent years, researchers have gained a deeper understanding of the mechanisms of necrosis and apoptosis in mammals. In addition, many new forms of lytic regulated cell death (RCD), such as pyroptosis, necroptosis and ferroptosis, have been discovered, thus enhancing our understanding of the molecular mechanisms of programmed cell death (PCD) and the associated signalling pathways as well as their relationship with diseases. However, our understanding of lytic RCD in fish is limited. Recently, some progress has been made regarding the induction conditions, expression of related genes and regulation of lytic RCD in fish. Furthermore, research on the roles of lytic RCD in tissue development, against pathogenic microorganism, inflammatory disease and neurological disease, has also been advanced. Understanding lytic RCD in fish will enable the regulation of its occurrence through human intervention to inhibit disease processes, improve fish health and explore possible countermeasures based on these basic theoretical studies. [ABSTRACT FROM AUTHOR]

Pregnant rats were treated intraperitoneally with a single dose of methotrexate (MTX) 90 mg/kg on gestation day (GD) 13, and fetal eyeballs were examined time-dependently from GD 13.5 to 15.5. Throughout the experimental period, the inner plate of the ocular cup in the MTX group was significantly thinner than that in the control group. In the inner plate of the ocular cup on GD 15 and 15.5, whereas a developed ganglion cell layer was observed in the control group, the ganglion cell layer in the MTX group was undeveloped and indistinguishable. Disturbance of the arrangement of lens fiber cells, narrowing of the hyaloid cavity of the optic cup, and hypoplasia of optic nerve fibers were observed in the MTX group on GD 15 and 15.5. Increase of pyknosis and decrease of mitosis were induced in the optic cup and the lens epithelium of the MTX group. In the inner plate of the optic cup and the lens epithelium of the MTX group, the cleaved caspase-3- and TUNEL-positive rates increased significantly throughout the experimental period. The phospho-histone H3-positive rate in the inner plate of the optic cup decreased significantly from GD 13.5 to 14.5, and it recovered on GD 15. On the other hand, the phospho-histone H3-positive rate in the lens epithelium decreased significantly throughout the experimental period. These results suggested that optic tissue on GD 13 in rats was sensitive to MTX. [ABSTRACT FROM AUTHOR]

We here describe a convenient method for preparation, fixation and fluorescence analysis of in vitro cultivated metacestode vesicles from E. multilocularis. Parasite materials could be prepared in one hour, did not need to be sectioned, and were subsequently utilized for further whole-mount staining assays directly. Using these preparations, in combination with conventional fluorescence staining techniques, we could detect the expression and subcellular localization of a specific protein and identify in situ proliferative or apoptotic cells in the germinal layer of metacestode vesicles. Based on this approach, future molecular and cellular analysis of Echinococcus metacestode vesicles in the in vitro system will be greatly facilitated. [ABSTRACT FROM AUTHOR]

Highlights: [•] We used Caenorhabditis elegans to investigate how TBTCL exhibits its effect on animal germline. [•] TBTCL exposure resulted in increased sterility and embryonic lethality. [•] TBTCL exposure induced increased DSBs and checkpoint activation in germline. [•] Germ cell apoptosis and proliferation arrest were induced by TBTCL exposure. [•] Checkpoint and p53 signaling pathways were found essential in response to TBTCL. [Copyright &y& Elsevier]

Cerium is widely used in many aspects of modern society, including agriculture, industry and medicine. It has been demonstrated to enter the ecological environment, is then transferred to humans through food chains, and causes toxic actions in several organs including the brain of animals. However, the neurotoxic molecular mechanisms are not clearly understood. In this study, mice were exposed to 0.5, 1, and 2 mg/kg BW cerium chloride (CeCl3) for 90 consecutive days, and their learning and memory ability as well as hippocampal gene expression profile were investigated. Our findings suggested that exposure to CeCl3 led to hippocampal lesions, apoptosis, oxidative stress and impairment of spatial recognition memory. Furthermore, microarray data showed marked alterations in the expression of 154 genes involved in learning and memory, immunity and inflammation, signal transduction, apoptosis and response to stress in the 2 mg/kg CeCl3 exposed hippocampi. Specifically, the significant up-regulation of Axud1, Cdc37, and Ube2v1 caused severe apoptosis, and great suppression of Adcy8, Fos, and Slc5a7 expression led to impairment of mouse cognitive ability. Therefore, Axud1, Cdc37, Ube2v1, Adcy8, Fos, and Slc5a7 may be potential biomarkers of hippocampal toxicity caused by CeCl3 exposure. [ABSTRACT FROM AUTHOR]

Abstract: A xenograft brain tumor model was established by the subcutaneous injection of U87MG cells into nude mice to investigate the efficacy of a non-viral vector, arginine-modified polyamidoamine dendrimer (PAMAM-R), in delivering a therapeutic gene, human interferon beta (IFN-β). We used 4′,6-diamidino-2-phenylindole staining, the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, and the caspase-3 activity assay to determine the induction of apoptosis upon transfection with the PAMAM-R/IFN-β gene polyplex in vitro. The polyplex was injected into xenograft brain tumors. Mice treated with PAMAM-R/pORF-IFN-β exhibited a significantly smaller tumor size than control mice and PAMAM-R/pORF treated mice. Hematoxylin/eosin staining and immunohistochemistry with the endothelial growth factor receptor antibody also revealed inhibition of tumor growth. Furthermore, reverse transcription polymerase chain reaction and the TUNEL assay also verified the expression of IFN-β and induction of apoptosis in vivo. These results indicate that the PAMAM-R/pORF-IFN-β polyplex is an effective therapeutic candidate for glioblastoma multiforme due to its selective induction of apoptosis in tumor cells. [Copyright &y& Elsevier]

Although liver toxicity induced by titanium dioxide nanoparticles (TiO2 NPs) has been demonstrated, very little is known about the molecular mechanisms of multiple genes working together underlying this type of liver injury in mice. In this study, we used the whole-genome microarray analysis technique to determine the gene expression profile in the livers of mice exposed to 10 mg/kg body weight TiO2 NPs for 90 days. The findings showed that long-term exposure to TiO2 NPs resulted in obvious titanium accumulation in the liver and TiO2 NP aggregation in hepatocyte nuclei, an inflammatory response, hepatocyte apoptosis, and liver dysfunction. Furthermore, microarray data showed striking changes in the expression of 785 genes related to the immune/inflammatory response, apoptosis, oxidative stress, the metabolic process, response to stress, cell cycle, ion transport, signal transduction, cell proliferation, cytoskeleton, and cell differentiation in TiO2 NP–exposed livers. In particular, a significant reduction in complement factor D (Cfd) expression following long-term exposure to TiO2 NPs resulted in autoimmune and inflammatory disease states in mice. Therefore, Cfd may be a potential biomarker of liver toxicity caused by TiO2 NPs exposure. [ABSTRACT FROM PUBLISHER]

Cerium has been demonstrated to damage liver of mice, but very little is known about the molecular mechanisms underlying the mouse liver apoptosis. In order to understand the liver injury induced by intragastric administration of cerium chloride (CeCl) for 60 consecutive days, the hepatocyte ultrasrtucture, various oxidative stress parameters, and the stress-related gene expression levels were investigated for the mouse liver. The results demonstrated that CeCl had an obvious accumulation in the mouse liver, leading to a classical laddering cleavage of DNA and hepatocyte apoptosis. CeCl significantly promoted the accumulation of reactive oxygen species and inhibited the stress-related gene expression of superoxide dismutase, catalase, glutathione peroxidase, metallothionein, heat-shock protein 70, glutathione- S-transferase, P53, and transferring, and it effectively activated the cytochrome p450 1A. It implied that CeCl resulted in apoptosis and alteration of expression levels of the genes related with metal detoxification/metabolism regulation and radical scavenging action in mice. [ABSTRACT FROM AUTHOR]

Ferroptosis is a type of nonapoptotic regulated cell death (RCD) manifesting as changes in the regulatory signaling of multiple organelles. Currently, part of the upstream execution mechanism of ferroptosis, namely, the production of unstable iron pools and/or the inhibition or inactivation of glutathione peroxidase 4 (GPX4), and the downstream trigger mechanism of lipid peroxide production and accumulation have been clarified. In addition, ferroptosis-related signaling molecules can undergo protein posttranslational modification to enable their participation in the regulation of signaling network functions. Our understanding of ferroptosis is based on observations of invertebrates and mammals. Although the ferroptosis mechanism in aquatic organisms and terrestrial organisms has been well conserved throughout evolution, some components of the ferroptosis pathway differ. As a newly discovered type of cell death, ferroptosis may be at the root of many diseases. Given that aquatic animal diseases present major challenges to the development of aquaculture, interest in ferroptosis has increased dramatically in recent years, and reports of iron-based programmed death of fish cells will continue to strengthen. Ferroptosis in fish can be mediated by human intervention, thereby providing a possible breakthrough for inhibiting disease processes and improving fish health. • The most recent discoveries concerning ferroptosis in aquaculture are overviewed. • Ferroptosis participated in resistance to toxins and pathogen invasion, development, and other mechanisms are included. • Future perspectives on the theoretical importance and value of ferroptosis research in aquaculture for application are proposed. [ABSTRACT FROM AUTHOR]

Sepsis-induced cardiac dysfunction (SICD) is one of the key complications in sepsis and it is associated with adverse outcomes and increased mortality. There is no effective drug to treat SICD. Previously, we reported that tubeimoside I (TBM) improved survival of septic mice. The aim of this study is to figure out whether TBM ameliorates SICD. Also, SIRT3 was reported to protects against SICD. Our second aim is to confirm whether SIRT3 plays essential roles in TBM's protective effects against SICD. Our results demonstrated that TBM could alleviate SICD and SICD's key pathological factor, inflammation, oxidative stress, and apoptosis were all reduced by TBM. Notably, SICD induced a significant decrease in cardiac SIRT3 expression, while TBM treatment could reverse SIRT3 expression. To clarify whether TBM provides protection via SIRT3, we injected a specific SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP) into mice before TBM treatment. Then the cardioprotective effects of TBM were largely abolished by 3-TYP. This suggests that SIRT3 plays an essential role in TBM's cardioprotective effects. In vitro , TBM also protected H9c2 cells against LPS-induced injury, and siSIRT3 diminished these protective effects. Taken together, our results demonstrate that TBM protects against SICD via SIRT3. TBM might be a potential drug candidate for SICD treatment. [ABSTRACT FROM AUTHOR]

Abstract: With their widespread application in agriculture, industry, culture, medicine, and daily life, lanthanide compounds are being brought into the ecological environment and human body through food chains. It is important to know the acute and chronic effects of lanthanides on the environment, nature balance, and the human body after their entry into bodies and the environment. Lanthanides have been demonstrated to cause spleen apoptosis and decreased immunity of mice, but very little is known about the molecular aspects of these mechanism. In order to understand the spleen apoptotic mechanism induced by intragastric administration of 2, 10 and 20mgkg−1 body weight CeCl3 for consecutive 60d, we investigated the cerium accumulation, apoptosis, the expression levels of the apoptosis-related cytokines into apoptosis-related genes and proteins. The results demonstrated that cerium had obvious accumulation in the mouse spleen, leading to the significant increase of the spleen indices and splenocyte apoptosis. Furthermore, CeCl3 could effectively activate caspase-3 and -9, decrease the Bcl-2 the levels of gene and protein, and increase the levels of Bax, and cytochrome c genes and their protein expressions, and promote reactive oxygen species production. It implied CeCl3-induced apoptosis in the mouse spleen via intrinsic pathway. Our findings suggest the need for great caution to handle the lanthanides for workers and consumers. [Copyright &y& Elsevier]

Abstract: Mucositis arising from cancer chemotherapy is a common problem for which there is no definitive treatment. 5-fluorouracil (5-FU) is a common cytotoxic agent used to treat solid tumors. A global gene expression array was performed to identify genetic signals involved in the pathogenesis of mucositis. The chemokine (C-X-C motif) ligand 9 (CXCL9) was one of the candidates identified that presented a characteristic gene expression profile; its temporal expression pattern was correlated with the damage and regeneration phases of the small intestine upon 5-FU chemotherapy. We found that prophylactic CXCL9 administration was able to attenuate the severity of mucositis, weight loss and diarrhea caused by chemotherapy. CXCL9 also increased the tolerance of the mice to lethal-dose chemotherapy. Moreover, we demonstrated that CXCL9 was able to promote the proliferation and regeneration of intestinal cells by inhibiting the proliferation of normal intestinal mucosal cells prior to chemotherapy and by reducing the 5-FU-induced apoptosis in intestinal crypts. Thus, pretreatment with CXCL9 is a new and promising strategy for the alleviation of chemotherapy-induced intestinal mucositis in clinical settings. [Copyright &y& Elsevier]