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Objective: 7,8-Dihydroxyflavone, a tyrosine kinase receptor agonist, is a flavonoid that has recently gained the attention of researchers due to its anticancer properties. Nevertheless, molecular pathways of 7,8-dihydroxyflavone for hepatocarcinoma are uncertain. Our aim was to identify the impact of 7,8-dihydroxyflavone on human hepatocarcinoma. Material and Methods: Human hepatocarcinoma cell line-7 cells were used as human hepatocarcinoma cells, and 7,8-dihydroxyflavone was applied to the cells at various doses. The cytotoxic and apoptotic effects of 7,8-dihydroxyflavone were determined with Alamar Blue and flow cytometry. The properties of 7,8-dihydroxyflavone on the mRNA expressions related with Bcl-2, Bax, cleaved-caspase-3 genes, and protein expressions were determined via quantitative real-time polymerase chain reaction and western blot analysis, respectively. Results: 7,8-D ihydr oxyfl avone -enha nced cell death in human hepatocarcinoma cell line-7 via the overexpression of cleaved-caspase-3 (P = .003) and decreased Bcl-2 (P = .038) protein levels. Furthermore, cleavedcaspase- 3 mRNA overexpression (P = .001) markedly led to 7,8-d ihydr oxyfl avone -indu ced apoptosis. Conclusion: 7,8-Dihydroxyflavone could promote apoptotic cell death by modulating caspase pathways and suppressing antiapoptotic protein. These characteristics may mediate to clinical practice of 7,8-dihydroxyflavone for prevention and therapy of hepatocarcinoma. [ABSTRACT FROM AUTHOR]

Hippocampal neurons undergo various forms of cell death after status epilepticus. Necrostatin-1 specifically inhibits necroptosis mediated by receptor interacting protein kinase 1 (RIP1) and RIP3 receptors. However, there are no reports of necroptosis in mouse models of status epilepticus. Therefore, in this study, we investigated the effects of necrostatin-1 on hippocampal neurons in mice with status epilepticus, and, furthermore, we tested different amounts of the compound to identify the optimal concentration for inhibiting necroptosis and apoptosis. A mouse model of status epilepticus was produced by intraperitoneal injection of kainic acid, 12 mg/kg. Different concentrations of necrostatin-1 (10, 20, 40, and 80 μM) were administered into the lateral ventricle 15 minutes before kainic acid injection. Hippocampal damage was assessed by hematoxylin-eosin staining 24 hours after the model was successfully produced. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, western blot assay and immunohistochemistry were used to evaluate the expression of apoptosis-related and necroptosis-related proteins. Necrostatin-1 alleviated damage to hippocampal tissue in the mouse model of epilepsy. The 40 μM concentration of necrostatin-1 significantly decreased the number of apoptotic cells in the hippocampal CA1 region. Furthermore, necrostatin-1 significantly downregulated necroptosis-related proteins (MLKL, RIP1, and RIP3) and apoptosis-related proteins (cleaved-Caspase-3, Bax), and it upregulated the expression of anti-apoptotic protein Bcl-2. Taken together, our findings show that necrostatin-1 effectively inhibits necroptosis and apoptosis in mice with status epilepticus, with the 40 μM concentration of the compound having an optimal effect. The experiments were approved by the Animal Ethics Committee of Fujian Medical University, China (approval No. 2016-032) on November 9, 2016.

Context: Caragana pruinosa Kom. (Fabaceae), a commonly used folk medicine, has been found to possess antitumor effects. However, the antiproliferative effect of 2,4-dihydroxy-3′-methoxy-4′-ethoxychalcone (DMEC) derived from C. pruinosa against multiple myeloma (MM) has never been investigated. Objective: This study systematically evaluates the antiproliferative effect of DMEC against MM cells. Materials and methods: The antiproliferative effect of DMEC (1, 2, 4, 8, 16, 32, and 64 μM) on MM cells lines, including RPMI8226, MM.1S, and U266, was examined using Cell counting kit-8 (CCK-8) assay after 24 h incubation. The proapoptotic effect of DMEC (20 μM) was determined using fluorescent microscope and flow cytometer, and its possible underlying mechanisms were further studied by using western blotting analysis. Results: The half maximal inhibitory concentrations (IC50) of DMEC on RPMI8226, MM.1S, and U266 cells were calculated as 25.97, 18.36, and 15.02 μM, respectively. The inhibitory effect of DMEC on MM cells was related to mitochondria-mediated apoptosis via upregulation of the cleaved-caspase-3 (C-3), cleaved-caspase-9 (C-9), Bad, and cytochrome C (Cyto C), but downregulation of the Bcl-2 and poly ADP-ribose polymerase (PARP). Furthermore, DMEC (5, 10, and 20 μM) reduced the expression of phosphatidylinositol-3-kinase (PI3K), phosphorylated (p)-protein kinase B (Akt), and p-mammalian target of rapamycin (p-mTOR), which were further evidenced by pretreatment with IGF-1, a PI3K activator. Conclusion: Collectively, our results indicate that the DMEC could be treated as a new candidate for treatment of multiple myeloma in the future. Also, an in vivo study is warranted in the future.

Context:Caragana pruinosa Kom. (Fabaceae), a commonly used folk medicine, has been found to possess antitumor effects. However, the antiproliferative effect of 2,4-dihydroxy-3′-methoxy-4′-ethoxychalcone (DMEC) derived from C. pruinosa against multiple myeloma (MM) has never been investigated. Objective: This study systematically evaluates the antiproliferative effect of DMEC against MM cells. Materials and methods: The antiproliferative effect of DMEC (1, 2, 4, 8, 16, 32, and 64 μM) on MM cells lines, including RPMI8226, MM.1S, and U266, was examined using Cell counting kit-8 (CCK-8) assay after 24 h incubation. The proapoptotic effect of DMEC (20 μM) was determined using fluorescent microscope and flow cytometer, and its possible underlying mechanisms were further studied by using western blotting analysis. Results: The half maximal inhibitory concentrations (IC50) of DMEC on RPMI8226, MM.1S, and U266 cells were calculated as 25.97, 18.36, and 15.02 μM, respectively. The inhibitory effect of DMEC on MM cells was related to mitochondria-mediated apoptosis via upregulation of the cleaved-caspase-3 (C-3), cleaved-caspase-9 (C-9), Bad, and cytochrome C (Cyto C), but downregulation of the Bcl-2 and poly ADP-ribose polymerase (PARP). Furthermore, DMEC (5, 10, and 20 μM) reduced the expression of phosphatidylinositol-3-kinase (PI3K), phosphorylated (p)-protein kinase B (Akt), and p-mammalian target of rapamycin (p-mTOR), which were further evidenced by pretreatment with IGF-1, a PI3K activator. Conclusion: Collectively, our results indicate that the DMEC could be treated as a new candidate for treatment of multiple myeloma in the future. Also, an in vivo study is warranted in the future. [ABSTRACT FROM AUTHOR]

Highlights • JNK signaling pathway is powerfully activated in P301L mice. • P-tau-induced spine injury is correlated by an increased level of JNK activation. • Synaptopathy, behavioral defects, P-JNK are well-correlated features in P301L tauopathy model. • The JNK activation shows a strong sexual dimorphism: higher in female vs male mice. Abstract Pathological Tau (P-Tau) leads to dementia and neurodegeneration in tauopathies, including Alzheimer's disease. The P301L transgenic mice well mimic human tauopathy features; P-Tau localizes also at the dendritic spine level and this correlates with synaptic markers down-regulation. Importantly, tg females present a more severe pathology compared to male mice. We describe JNK activation in P301L-tg mice, characterizing by P-JNK and P-c-Jun, cleaved-Caspase-3, P-PSD95 and P-Tau (direct JNK-targets) increased levels in tg vs control mice. These data indicate that JNK stress pathway is involved in neuronal degenerative mechanisms of this mouse model. In addition, P-JNK level is higher in females compared to male tg mice, underlying a sexual dimorphism in the JNK pathway activation. The behavioral studies highlight that tg females present major cognitive and locomotor defects, strongly correlated with a more severe synaptic injury, in comparison to tg male. Notably, at the dendritic spine level, JNK is powerfully activated and its level reveals a sexual dimorphism that is coherent with behavioral defects and spine pathology. The P301L's synaptic pathology is characterized by a strong increase of P-PSD95/PSD95 and P-JNK/JNK ratios and by an augmented level of cleaved-Caspase-3 and a decrease of Drebrin level in the post-synaptic elements. These results suggest that JNK plays a key role in synaptopathy of P301L mice. Importantly, until now, there are any efficient treatments against synaptic pathology and JNK could represent an interesting target to tackle P-Tau-induced synaptic pathology. It will be important to test specific JNK inhibitors to verify their potential neuroprotective effect. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) may be a significant risk factor for development of neurodegenerative disorders such as chronic traumatic encephalopathy (CTE), post-traumatic epilepsy (PTE), and Alzheimer's (AD) and Parkinson's (PD) diseases. Chronic TBI is associated with several pathological features that are also characteristic of neurodegenerative diseases, including tau pathologies, caspase-3-mediated apoptosis, neuroinflammation, and microvascular alterations. The goal of this study was to evaluate changes following TBI in cleaved-caspase-3 and caspase-3-cleaved tau truncated at Asp421, and their relationships to cellular markers potentially associated with inflammation and blood-brain (BBB) barrier damage. We studied astrocytes (glial fibrillary acidic protein [GFAP]), microglia (ionized calcium-binding adapter molecule 1 [Iba1]), BBB (endothelial barrier antigen [EBA]), and activated microglia/macrophages (cluster of differentiation 68 [CD68]). We employed immunohistochemistry at different time points from 24 h to 3 months after controlled cortical impact (CCI) injury in rats, with particular interest in white matter. The study demonstrated that CCI caused chronic upregulation of cleaved-caspase-3 in the white matter of the corpus callosum. Increases in cleaved-caspase-3 in the corpus callosum were accompanied by accumulation of caspase-3-cleaved tau, with increasing perivascular aggregation 3 months after CCI. Immunofluorescence experiments further showed cellular co-localization of cleaved-caspase-3 with GFAP and CD68 and its adjacent localization with EBA, suggesting involvement of apoptosis and neuroinflammation in mechanisms of delayed BBB and microvascular damage that could contribute to white matter changes. This study also provides the first evidence that evolving upregulation of cleaved-caspase-3 is associated with accumulation of caspase-3-cleaved tau following experimental TBI, thus providing new insights into potential common mechanisms mediated by caspase-3 and underlying chronic TBI pathologies and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is associated with long-term disabilities and devastating chronic neurological complications including problems with cognition, motor function, sensory processing, as well as behavioral deficits and mental health problems such as anxiety, depression, personality change and social unsuitability. Clinical data suggest that disruption of the thalamo-cortical system including anatomical and metabolic changes in the thalamus following TBI might be responsible for some chronic neurological deficits following brain trauma. Detailed mechanisms of these pathological processes are not completely understood. The goal of this study was to evaluate changes in the thalamus following TBI focusing on cleaved-caspase-3, a specific effector of caspase pathway activation and myelin and microvascular pathologies using immuno- and histochemistry at different time points from 24 h to 3 months after controlled cortical impact (CCI) in adult Sprague-Dawley rats. Significant increases in cleaved-caspase-3 immunoreactivity in the thalamus were observed starting one month and persisting for at least three months following experimental TBI. Further, the study demonstrated an association of cleaved-caspase-3 with the demyelination of neuronal processes and tissue degeneration in the gray matter in the thalamus, as reflected in alterations of myelinated fiber integrity (luxol fast blue) and decreases in myelin basic protein (MBP) immunoreactivity. The immunofluorescent counterstaining of cleaved-caspase-3 with endothelial barrier antigen (EBA), a marker of blood-brain barrier, revealed limited direct and indirect associations of cleaved caspase-3 with blood-brain barrier damage. These results demonstrate for the first time a significant chronic upregulation of cleaved-caspase-3 in selected thalamic regions associated with cortical regions directly affected by CCI injury. Further, our study is also the first to report that significant upregulation of cleaved-caspase-3 in selected ipsilateral thalamic regions is associated with microvascular reorganization reflected in the significant increases in the number of microvessels with blood-brain barrier alterations detected by EBA staining. These findings provide new insights into potential mechanisms of TBI cell death involving chronic activation of caspase-3 associated with disrupted cortico-thalamic and thalamo-cortical connectivity. Moreover, this study offers the initial evidence that this upregulation of activated caspase-3, delayed degeneration of myelinated nerve fibers and microvascular reorganization with impaired blood-brain barrier integrity in the thalamus might represent reciprocal pathological processes affecting neuronal networks and brain function at the chronic stages of TBI.

Streptococcus pneumoniae is the causative agent of numerous diseases including severe invasive infections such as bacteremia and meningitis. It has been previously shown that strains of S. pneumoniae that are unable to survive in the bloodstream may colonize the CNS. However, information on cellular components and pathways involved in the neurotropism of these strains is still scarce. The olfactory system is a specialized tissue in which olfactory receptor neurons (ORNs) are interfacing with the external environment through several microvilli. Olfactory ensheathing cells (OECs) which also form the glial limiting membrane at the surface of the olfactory bulb (OB) are the only cells that ensheathe the ORNs axons. Since previous data from our group showed that OECs may harbor S. pneumoniae , we decided to test whether infection of the OB or OEC cultures modulates the expression levels of neurotrophic factor’s mRNA and its putative effects on the activation and viability of microglia. We observed that neurotrophin-3 (NT-3) and glial cell-line-derived neurotrophic factor (GDNF) expression was significantly higher in the OB from uninfected mice than in infected mice. A similar result was observed when we infected OEC cultures. Brain-derived neurotrophic factor (BNDF) expression was significantly lower in the OB from infected mice than in uninfected mice. In contrast, in vitro infection of OECs resulted in a significant increase of BDNF mRNA expression. An upregulation of high-mobility group box 1 (HMGB1) expression was observed in both OB and OEC cultures infected with S. pneumoniae . Moreover, we found that conditioned medium from infected OEC cultures induced the expression of the pro-apoptotic protein cleaved-caspase-3 and an apparently continuous nuclear factor-kappa B (NF- κ B) p65 activation in the N13 microglia. Altogether, our data suggest the possible existence of an OEC–pathogen molecular interface, through which the OECs could interfere on the activation and viability of microglia, favoring the access of non-hematogenous S. pneumoniae strains to the CNS in the absence of bacteremia. [ABSTRACT FROM AUTHOR]

Abstract: Ovarian follicle atresia is a common phenomenon in vertebrate ovaries and this process is characterized by follicular wall degeneration. The molecular mechanism underlying follicle atresia is apoptotic granulusa cell death; however, the exact signaling pathway is still unclear. PARP-1, the founding member of the poly (ADP-ribose) polymerase (PARP) family, plays an important role in a large variety of physiological processes. Although its cleavage has recently been implicated in a variety of physiological and pathological processes, its role in the process of follicular atresia is not yet completely defined. We identified the cleavage of PARP-1 involved in the process of follicle degeneration, which is known as “follicular atresia”, both from in vivo models and cell culture data. The results from immunohistochemistry (IHC) showed that cleaved PARP-1 was mainly located in apoptotic granulosa cells (GCs); and the expression of PARP-1 and caspase-3 were decreased in apoptotic granulosa cells (GCs). The results from western blotting showed that PARP-1 expression was significantly decreased in atretic follicles compared with healthy (H) follicles, and the cleavage of caspase-3 (17kDa) significantly increased in atretic follicles. Along with the cleavage of caspase-3, the expression of cleaved PARP-1 (24kDa) product was significantly increased, which confirmed caspase-3 activation. Serum starvation led to a reduction in PARP-1 and an increase in cleaved PARP-1 (24kDa) and caspase-3 (17kDa), suggesting that caspase-3 was activated under the stress of withdrawal of growth factors, in accordance with the in vivo study. In the present study, the concentrations of estradiol (E2) and progesterone (P4) as well as the P4/E2 (P/E) ratio were combined with morphological features to determine follicular classification. In summary, the present study demonstrated that cleavage of PARP-1 by caspase-3 was involved in the process of granulosa cell apoptosis. PARP-1 may through its cleavage act as a critical regulator in the process of porcine follicular atresia. Our results identified that cleavage of PARP-1 by activated (cleaved) caspase-3 may serve a key role in controlling follicular atresia through granulosa cell degeneration. These findings should prove helpful in understanding the regulatory mechanisms controlling follicular development and atresia. [Copyright &y& Elsevier]

The cleaved-Caspase-3 antibody is a popular tool in apoptosis research in Drosophila. As the antibody was raised against cleaved human Caspase-3, it was assumed that it detects cleaved DRICE and DCP-1, Caspase-3-like effector caspases in Drosophila. However, as shown here, strong immunoreactivity persists in apoptotic models doubly mutant for drICE and dcp-1. In contrast, mutants of the apoptosome components DRONC (Caspase-9-like) and ARK (Apaf-1 related) do not label with the cleaved-Caspase-3 antibody. By peptide blocking experiments and further genetic studies, we provide evidence that the cleaved-Caspase-3 antibody recognizes multiple proteins including DCP-1 and likely DRICE, but also at least one additional unknown protein, all of which require DRONC for epitope exposure. The unknown substrate may be involved in non-apoptotic functions of DRONC. Because the cleaved-Caspase-3 antibody not only detects cleaved Caspase-3-like proteins in Drosophila, but also other proteins in a DRONC-dependent manner, it is more accurate to consider the cleaved-Caspase-3 antibody as a marker for DRONC activity, rather than effector caspase activity. [ABSTRACT FROM AUTHOR]

The development of chemotherapeutic dug resistance hinders the clinical treatment of cancer. MicroRNAs (miRNAs/miRs) have been revealed to serve essential roles in the drug resistance of numerous types of cancer. miR-139-5p was previously reported to be associated with cisplatin (DDP) sensitivity in human nasopharyngeal carcinoma cells and colorectal cancer cells. However, the effect and underlying mechanism of miR-139-5p in DDP sensitivity in non-small cell lung cancer (NSCLC) cells has not yet been fully elucidated. In the present study, the expression of miR-139-5p and Homeobox protein Hox-B2 (HOXB2) in NSCLC tissues was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Subsequently, the effect of miR-139-5p on the DDP sensitivity of NSCLC cells in vitro was investigated. Cell proliferation was examined using a Cell Counting Kit-8 assay. Western blotting was used to evaluate the protein expression of HOXB2, phosphorylated (p)-PI3K, p-AKT, caspase-3 and cleaved-caspase-3, and RT-qPCR was used to evaluate the expression of miR-139-5p, and the mRNA expression levels of HOXB2, PI3K, AKT and caspase-3. The apoptotic rate of the cells was detected using flow cytometry. miR-139-5p expression in NSCLC tissues was shown to be significantly lower compared with that in adjacent tissues. Additionally, miR-139-5p increased cell apoptosis and inhibited NSCLC cell proliferation induced by DDP in vitro via modulating the PI3K/AKT/caspase-3 signaling pathway. Furthermore, HOXB2 was identified to be a target of miR-139-5p, and miR-139-5p was revealed to sensitize NSCLC cells to DDP via the targeting of HOXB2. Taken together, the results of the present study demonstrated that regulating the expression of miR-139-5p could provide a novel approach to reverse DDP resistance and increase chemosensitivity in the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Hippocampal neurons undergo various forms of cell death after status epilepticus. Necrostatin-1 specifically inhibits necroptosis mediated by receptor interacting protein kinase 1 (RIP1) and RIP3 receptors. However, there are no reports of necroptosis in mouse models of status epilepticus. Therefore, in this study, we investigated the effects of necrostatin-1 on hippocampal neurons in mice with status epilepticus, and, furthermore, we tested different amounts of the compound to identify the optimal concentration for inhibiting necroptosis and apoptosis. A mouse model of status epilepticus was produced by intraperitoneal injection of kainic acid, 12 mg/kg. Different concentrations of necrostatin-1 (10, 20, 40, and 80 μM) were administered into the lateral ventricle 15 minutes before kainic acid injection. Hippocampal damage was assessed by hematoxylin-eosin staining 24 hours after the model was successfully produced. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, western blot assay and immunohistochemistry were used to evaluate the expression of apoptosis-related and necroptosis-related proteins. Necrostatin-1 alleviated damage to hippocampal tissue in the mouse model of epilepsy. The 40 μM concentration of necrostatin-1 significantly decreased the number of apoptotic cells in the hippocampal CA1 region. Furthermore, necrostatin-1 significantly downregulated necroptosis-related proteins (MLKL, RIP1, and RIP3) and apoptosis-related proteins (cleaved-Caspase-3, Bax), and it upregulated the expression of anti-apoptotic protein Bcl-2. Taken together, our findings show that necrostatin-1 effectively inhibits necroptosis and apoptosis in mice with status epilepticus, with the 40 μM concentration of the compound having an optimal effect. The experiments were approved by the Animal Ethics Committee of Fujian Medical University, China (approval No. 2016-032) on November 9, 2016., Competing Interests: None

Traumatic brain injury (TBI) is associated with long-term disabilities and devastating chronic neurological complications including problems with cognition, motor function, sensory processing, as well as behavioral deficits and mental health problems such as anxiety, depression, personality change and social unsuitability. Clinical data suggest that disruption of the thalamo-cortical system including anatomical and metabolic changes in the thalamus following TBI might be responsible for some chronic neurological deficits following brain trauma. Detailed mechanisms of these pathological processes are not completely understood. The goal of this study was to evaluate changes in the thalamus following TBI focusing on cleaved-caspase-3, a specific effector of caspase pathway activation and myelin and microvascular pathologies using immuno- and histochemistry at different time points from 24 h to 3 months after controlled cortical impact (CCI) in adult Sprague-Dawley rats. Significant increases in cleaved-caspase-3 immunoreactivity in the thalamus were observed starting one month and persisting for at least three months following experimental TBI. Further, the study demonstrated an association of cleaved-caspase-3 with the demyelination of neuronal processes and tissue degeneration in the gray matter in the thalamus, as reflected in alterations of myelinated fiber integrity (luxol fast blue) and decreases in myelin basic protein (MBP) immunoreactivity. The immunofluorescent counterstaining of cleaved-caspase-3 with endothelial barrier antigen (EBA), a marker of blood-brain barrier, revealed limited direct and indirect associations of cleaved caspase-3 with blood-brain barrier damage. These results demonstrate for the first time a significant chronic upregulation of cleaved-caspase-3 in selected thalamic regions associated with cortical regions directly affected by CCI injury. Further, our study is also the first to report that significant upregulation of cleaved-caspase-3 in selected ipsilateral thalamic regions is associated with microvascular reorganization reflected in the significant increases in the number of microvessels with blood-brain barrier alterations detected by EBA staining. These findings provide new insights into potential mechanisms of TBI cell death involving chronic activation of caspase-3 associated with disrupted cortico-thalamic and thalamo-cortical connectivity. Moreover, this study offers the initial evidence that this upregulation of activated caspase-3, delayed degeneration of myelinated nerve fibers and microvascular reorganization with impaired blood-brain barrier integrity in the thalamus might represent reciprocal pathological processes affecting neuronal networks and brain function at the chronic stages of TBI.

Oxidative stress is a critical factor in the pathophysiology of diabetic kidney disease. Previous study shows that hyperglycaemia aggravates renal injury through oxidative stress in diabetic model, and antioxidants have beneficial effect on diabetic kidney disease. However, the role of antioxidants in the progression of diabetic kidney disease is poorly understood. The aim of this study was to clarify whether zeaxanthin, an antioxidant, could ameliorate mesangial cell injury and if so, identify the related mechanism underlying this protective effect. To that end, superoxide dismutase (SOD) activity and methane dicarboxylic aldehyde (MDA) levels were measured by an assay kit, and mesangial cell apoptosis and ROS levels were assessed using flow cytometry analysis. Furthermore, The levels of a phosphorylated ser/thr protein kinase (p-AKT), phosphorylated glycogen synthase kinase-3 beta (p-GSK-3β), Bcl-2 associated X protein (Bax) and cleaved cysteinyl aspartate-specific proteinase-3 (caspase-3) were detected by western blot. We found that zeaxanthin decreases MDA levels and increased SOD activity, as well as inhibits apoptosis and decreases ROS levels in mesangial cells in a high sugar environment. Furthermore, zeaxanthin increased p-AKT levels while decreased the levels of p-GSK-3β, Bax and cleaved-caspase-3. In addition, LY294002 reversed the protective effect of zeaxanthin on mesangial cells. In conclusion, zeaxanthin ameliorated mesangial cell apoptosis may be involved in inhibiting oxidative stress through activating of the AKT signalling pathway., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)