SUMMARY Production of reactive oxygen species (ROS) increases with neuronal activity that accompanies synaptic development and function. Transcription-related factors and metabolic enzymes that are expressed in all tissues have been described to counteract neuronal ROS to prevent oxidative damage. Here, we describe the antioxidant gene LanCL1 that is prominently enriched in brain neurons. Its expression is developmentally regulated and induced by neuronal activity, neurotrophic factors implicated in neuronal plasticity and survival, and oxidative stress. Genetic deletion of LanCL1 causes enhanced accumulation of ROS in brain, and development-related lipid, protein, and DNA damage, mitochondrial dysfunction and apoptotic neurodegeneration. LanCL1 transgene protects neurons from ROS. LanCL1 protein purified from eukaryotic cells catalyzes the formation of thioether products similar to glutathione S-transferase. These studies reveal a neuron-specific glutathione defense mechanism that is essential for neuronal function and survival.

ObjectivesWe conducted a systematic review and meta-analysis of observational case-control studies to evaluate markers of oxidative stress in seminal plasma of patients with male infertility.BackgroundCurrent evidence links oxidative stress to male infertility, in which multiple markers of oxidative stress have been widely detected, publishing inconsistent results with regard to the role of oxidative stress markers in the evaluation of male infertility. Therefore, a systematic review and meta-analysis on this issue is necessary.ResultsFrom the 1024 articles initially retrieved, 65 studies were included in our meta-analysis with 11 oxidative stress markers, containing 3819 male infertility patients and 2012 controls. The concentrations of malondialdehyde (SMD = 1.86, p < 0.00001), NO (SMD = 0.89, p = 0.001), carbonyl protein (SMD = 2.09, p < 0.00001) in seminal plasma were significantly higher in infertility patients. The concentrations of GSH (SMD = –1.68, p < 0.00001), vitamin C (SMD = –1.12, p < 0.00001), and vitamin E (SMD = –1.48, p = 0.003), as well as the activities of catalase (SMD = –1.91, p < 0.0001), glutathione peroxidase (SMD = –1.96, p = 0.0002) and glutathione-S-transferase (SMD = –1.62, p = 0.009) declined remarkably, resulting in decreased total antioxidant capacity (SMD = –1.77, p < 0.00001). Besides, the activity of superoxide dismutase showed no statistical difference between infertility patients and controls (SMD = –0.51, p = 0.07).ConclusionsOur meta-analysis suggests that oxidative stress in seminal plasma resulting from decreased antioxidant defense are associated with male infertility.MethodsUsing PubMed, EMBASE, CNKI, VIP, and Wanfang database, we searched for literature reporting the detection of oxidative stress markers in the seminal plasma of male infertility published up to June 2017. Standardized mean differences (SMDs) and 95% confidence intervals (95%CI) were calculated for the finally analysis.

The high recurrence frequency of gliomas but deficiency of effective treatment and prevalent chemoresistance have elicited interests in exploring and developing new agents. Paris polyphyllins are monomers extracted from rhizome of Paris polyphylla var. yunnanensis. Here, we first reported that polyphyllin VII (PP7) exhibited cytotoxic effect on glioma cells. PP7 significantly suppressed the viability and induced cell death of U87-MG and U251 cells after 24 h, with the IC50 values 4.24 ± 0.87 μM and 2.17 ± 0.14 μM, respectively. Both apoptotic and autophagic processes were involved in the cytotoxic effect of PP7, as PP7 activated the Bcl2/Bax pathway and the inhibition of autophagy partly rescued the toxicity of PP7 in glioma cells. In addition, an inhibition of AKT/mTORC1 activity was found after PP7 administration, and it seemed that the overproduction of reactive oxygen species (ROS) was responsible for this effect. Namely, the removal of ROS by NAC treatment mitigated PP7-induced cell death, autophagy, and its effect on the AKT/mTORC1 signaling. Additionally, a combination assay of PP7 with temozolomide (TMZ), the most used chemotherapy for glioma patients, was performed resulting in synergism, while PP7 reduced TMZ resistance through inhibition of MGMT expression. Thus, our study reports PP7 as a potential agent for glioma treatment and reveals its underlying mechanisms of action.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. Improving neuronal survival in ALS remains a significant challenge. Previously, we identified Lanthionine synthetase C-like protein 1 (LanCL1) as a neuronal antioxidant defense gene, the genetic deletion of which causes apoptotic neurodegeneration in the brain. Here, we report in vivo data using the transgenic SOD1 G93A mouse model of ALS indicating that CNS-specific expression of LanCL1 transgene extends lifespan, delays disease onset, decelerates symptomatic progression, and improves motor performance of SOD1 G93A mice. Conversely, CNS-specific deletion of LanCL1 leads to neurodegenerative phenotypes, including motor neuron loss, neuroinflammation, and oxidative damage. Analysis reveals that LanCL1 is a positive regulator of AKT activity, and LanCL1 overexpression restores the impaired AKT activity in ALS model mice. These findings indicate that LanCL1 regulates neuronal survival through an alternative mechanism, and suggest a new therapeutic target in ALS.