Associations between meteorological variation and rupture of intracranial aneurysm in Fujian, China: A 5-year multicenter study.

OBJECTIVE: By exploring the exposure-response relationships between meteorological factors and rupture of intracranial aneurysm (IA) to reveal the influence of meteorological variation on IA rupture under the specific climate in Fujian, China. METHOD: 7515 cases of IA rupture from several municipal medical institutions in Fujian Province as well as local meteorological data during the same period were collected from 2013 to 2017. Poisson regression and Spearman correlation analysis were applied to explore the distribution characteristics of IA rupture and how it is associated with meteorological parameters. Poisson generalized additive model was established to further analyze the exposure-response relationships between meteorological factors and IA rupture, and its hysteresis effects. RESULT: The IA rupture exhibited a negative correlation with temperature (rs = -0.323, 95% CI: -0.539 ~ -0.068) and a positive correlation with atmospheric pressure (rs = 0.397, 95% CI: 0.152-0.597) or pressure difference (rs = 0.296, 95% CI: 0.038-0.517), 21.05 â„ƒ and 1000.14 hPa were the risk thresholds for the onset ascribed to variation in temperature and atmospheric pressure, respectively. Temperature and atmospheric pressure also exerted hysteresis effects on IA rupture. Cold will increase the rupture risk in the subsequent 1-3 days, and high pressure will raise the morbidity in the next 1-2 days. Besides, drastic variations in temperature and atmospheric pressure were also associated with the higher risk of IA rupture in the next 2 days and 1 day, respectively. CONCLUSION: Temperature and atmospheric pressure have a negative and positive correlation with IA rupture in Fujian, China, respectively. Variation in temperature and atmospheric pressure exert different degrees of hysteresis effects on IA rupture.

Targeting Mitochondrial Dysfunction With LncRNAs in a Wistar Rat Model of Chronic Obstructive Pulmonary Disease.

BACKGROUND/AIM: Chronic obstructive pulmonary disease (COPD) has become a prominent healthcare issue in recent years. Cigarette smoking (CS) and fine particulate matter (PM2.5) are important causative factors for COPD. This study assessed the aberrant lncRNA profiles in the tissue of rats with COPD caused by CS or PM2.5 Materials and Methods: A COPD rat model was developed using CS (CSM) or PM2.5 (PMM), and lung tissue RNA was extracted. The Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) were used to investigate the correlations between the distinct lncRNAs and mRNA pathways. A coding-non-coding gene co-expression network (CNC) was constructed by establishing connections between differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) associated with mitochondrial dysfunction and the inflammatory response. RESULTS: A quantitative real-time reverse transcription PCR (qRT-PCR) experiment was performed to verify the expression of the particular lncRNAs. Microarray analysis of lung tissue from the COPD model revealed that 123 and 444 lncRNAs were substantially raised and reduced in PMM vs. the control group (Ctrl), respectively, as were 621 and 1,178 mRNAs. Meanwhile, 81 and 340 lncRNAs were consistently raised and lowered in CSM vs. Ctrl, respectively, as were 408 and 931 mRNAs. GO enrichment and KEGG pathway analysis indicated that the COPD model was connected to inflammatory responses, mitochondrial dysfunction, and others. CONCLUSION: XR_340674, ENSRNOT00000089642, XR_597045, and XR_340651 were decreased, and XR_592469 was elevated. These lncRNAs were shown to be related to mitochondrial dysfunction in the lung tissue of animals exposed to CS or PM2.5.

The mediating and moderating role of personal strain and coping resource in the relationship between work stressor and quality of life among Chinese nurses.

OBJECTIVE: To determine whether personal strain and coping resources act as either mediator or moderator or both in the relationship between work stressor and quality of life among Chinese nurses. METHODS: A total of 1,012 nurses were selected from eight hospitals located in two provinces in China. Quality of life was measured with the Chinese version of the Short Form-36 Health Survey; work stressor, personal strain, and coping resources were evaluated using the Occupation Stress Inventory-Revised Edition. The hierarchical multiple regression procedure and Baron and Kenny's model of mediation were applied to test for moderation and mediation, respectively. A structural equation model was fit to assess the interrelationships among these variables. RESULTS: Work stressor was closely associated with quality of life, which was mediated and moderated by personal strain and coping resources. Personal strain also acted both as moderator and mediator in the relationship between coping resources and quality of life. The relationships were verified in the structural equation model. The greatest absolute value of the standardized total effects was seen in personal strain (0.817), followed by work stressor (0.634) and coping resources (0.488). CONCLUSIONS: Personal strain and coping resources have both mediating and moderating effects on the relationship between work stress and quality of life in a sample of Chinese nurses. An effective intervention strategy is needed to reduce work stress and ensure better quality of life.

Delicaflavone Represses Lung Cancer Growth by Activating Antitumor Immune Response through N6-Methyladenosine Transferases and Oxidative Stress.

Our previous studies have shown that delicaflavone (DLL), a biocomponent extracted from Selaginella doederleinii Hieron, has antitumor activity. However, the role of DLL in the antitumor immune response is unknown. In this study, we tested the potential roles of DLL in antitumor immune response. An animal tumor model with Lewis lung cancer cell line (3LL) in C57BL/6 mice was established to determine whether DLL induced the tumor-bearing host's antitumor immune response. m6A-MeRIP-qPCR, western blot, and flow cytometry were performed to explore the underlying mechanisms. DLL inhibited the proliferation of 3LL lung cancer cells in vitro and in vivo and induced tumor cell oxidative stress. DLL significantly inhibited tumor growth in immunocompetent mice compared with nude mice. DLL treatment significantly increased Th1 cytokine production and CD8+ T cell infiltration into tumor tissues in tumor-bearing mice. DLL-mediated antitumor immune effects were reversed by overexpression of the N6-methyladenosine (m6A) transferase Mettl3/Mettl14. Mechanistically, DLL upregulated the expression of Stat1 and Irf1 and the secretion of cytokines by inhibiting Mettl3 and Mettl14 in lung cancer cells. In conclusion, DLL inhibited lung cancer cell growth by suppressing Mettl3/Mettl14 to activate antitumor immunity. These findings provided an opportunity to enhance lung cancer immunotherapy.

Involvement of NEAT1/PINK1-mediated mitophagy in chronic obstructive pulmonary disease induced by cigarette smoke or PM2.5.

Background: This study sought to explore the underlying mechanism of long non-coding ribonucleic acid nuclear enriched abundant transcript 1 (NEAT1) and PTEN-induced kinase 1 (PINK1)-mediated mitophagy in chronic obstructive pulmonary disease (COPD) induced by cigarette smoke (CS) or fine particular matter (PM2.5). Methods: In total, 30 male Wistar Rats were divided into the following 3 groups: (I) the COPD group exposed to CS (CSM); (II) the COPD group exposed to PM2.5 (PMM); and (III) the control (Ctrl) group. Pulmonary function, the enzyme-linked immunoassay analysis results, the histopathology results, and the ultrastructures of the lung tissues were examined in the 3 groups, and NEAT1 expression levels and the mitophagy-related protein PINK1, Parkin, LC3B, and p62 levels were assessed by quantitative reverse transcription PCR (RT-qPCR) and Western blotting. The A549 cells were transfected with small interfering ribonucleic acid (siRNA) targeting NEAT1, and subsequently stimulated with CS extract (CSE) and PM2.5 suspension (PMS). Mitochondrial dysfunction and enhanced mitophagy were observed, and the expression of the NEAT1/PINK1 pathway was assessed by RT-qPCR and Western blotting. Results: Both the CSM and PMM groups had a lower tidal volume (VT), minute ventilation (MV), and a higher respiratory rate (f) than the Ctrl group. The interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha levels in the serum and bronchoalveolar lavage fluid of the CSM and PMM groups were significantly increased. The histological examination results revealed airway remodeling, the formation of pulmonary bullae, and emphysema in the CSM and PMM groups. Subsequently, the ultrastructures of the lung tissues in the CSM and PMM groups showed mitochondrial swelling and autophagosomes. Additionally, NEAT1 expression, the level of the mitophagy-related protein PINK1, Parkin, and the ratio of LC3-II/I increased synchronously. Further, NEAT1 siRNA blocked PINK1 expression, inhibited mitochondrial dysfunctions, and mitophagy activation in the A549 cells exposed to CSE or PMS. Conclusions: Our results suggest that CS and PM2.5 exposure induce mitochondrial dysfunction, and the NEAT1/PINK1 pathway plays a critical role in the occurrence and development of COPD by regulating mitophagy.

A glutamatergic basal forebrain to midbrain circuit mediates wakefulness and defensive behavior.

Defensive behavior, a group of responses that evolved due to threatening stimuli, is crucial for animal survival in the natural environment. For defensive measures to be timely and successful, a high arousal state and immediate sleep-to-wakefulness transition are required. Recently, the glutamatergic basal forebrain (BF) has been implicated in sleep-wake regulation; however, the associated physiological functions and underlying neural circuits remain unknown. Here, using in vivo fiber photometry, we found that BF glutamatergic neuron is activated by various threatening stimuli, including predator odor, looming threat, sound, and tail suspension. Optogenetic activation of BF glutamatergic neurons induced a series of context-dependent defensive behaviors in mice, including escape, fleeing, avoidance, and hiding. Similar to the effects of activated BF glutamatergic cell body, photoactivation of BF glutamatergic terminals in the ventral tegmental area (VTA) strongly drove defensive behaviors in mice. Using synchronous electroencephalogram (EEG)/electromyogram (EMG) recording, we showed that photoactivation of the glutamatergic BF-VTA pathway produced an immediate transition from sleep to wakefulness and significantly increased wakefulness. Collectively, our results clearly demonstrated that the glutamatergic BF is a key neural substrate involved in wakefulness and defensive behaviors, and encodes these behaviors through glutamatergic BF-VTA pathway. Overexcitation of the glutamatergic BF-VTA pathway may be implicated in clinical psychiatric diseases characterized by exaggerated defensive responses, such as autism spectrum disorders.

[Induction of cell damage and change of miR-133b expression by paraquat in PC12 cells].

OBJECTIVE: To investigate the effect of paraquat on induction of cell damage and miR-133b expression in PC12 cells. METHODS: Cytotoxicity of PC12 cells was measured by MTT assay, following the PC12 cells treatment with 50, 100, or 300 µmol/L paraquat. Cell apoptosis was examined by the method of Annexin V-FITC/PI in flow cytometry (FCM) and the relative level of miR-133b expression was measured by real time RT-PCR, following the PC12 cells treatment with 100 or 300 µmol/L paraquat. RESULTS: Survival rate of PC12 cells treated with 100 or 300 µmol/L paraquat was lower than that of the vehicle control group (P < 0.01, P < 0.05), in the dose dependent pattern. Apoptotic rate of PC12 cells treated with 100, 300 µmol/L paraquat was higher than that of the vehicle control group (P < 0.05). The relative level of miR-133b expression of PC12 cells treated with 300 µmol/L paraquat was higher than that of the vehicle control group (P < 0.05). CONCLUSIONS: Paraquat may cause cell damage and induce apoptosis in PC12 cells, and induce miR-133b expression.

[Effects of the workplace violence on the sub-health status of nurses].

OBJECTIVE: To explore the effects of workplace violence on sub-health status of nurses and to provide the theoretical basis for preventing the workplace violence in the hospitals and improving the health status of nurses. METHODS: A total of 679 nurses were selected by using stratified cluster sampling method. The Chinese version of workplace violence scale (WVS) and sub-health scale were used to measure workplace violence and sub-health status, respectively. RESULTS: The subjects with middle age (30-45 years) were found to have the highest incidence of physical assault (24.5%) and emotional assault (52.2%) as compared with other subjects (P<0.05). The prevalence (23.6%) of emotional assault of subjects with lowest education levels was significantly lower than that of others (P<0.05). The nurses with work shift were more vulnerable to emotional assault (45.1%) than those without work shift (36.8%)(P<0.05). The prevalence of the workplace violence of nurses in the psychiatric department and emergency department was significantly higher than that of nurses in other departments (P<0.05). The results of multivariate analysis showed that workplace violence was an important risk factor for sub-health status of nurses when other potential confounding factors were taken into account. CONCLUSION: The results of present study showed that workplace violence plays an important role in sub-health status of nurses after adjusting other potential confounding factors. It is important to develop the prevention strategies for reducing the incidence of workplace violence and improving the sub-health status of nurses.

[Antagonism of tert-butylhydroquinone on neurotoxicity and oxidative stress induced by paraquat in PC12].

OBJECTIVE: To investigate the protective effects of the tert-butylhydroquinone (tBHQ) pretreatment on neurotoxicity and oxidative stress induced by paraquat (PQ) in PC12 cells. METHODS: Cytotoxicity of PC12 cells was measured by MTT assay, following the PC12 cells treatment with different concentrations of 100, 300 micromol/L PQ for 24 h and 48 h. PC12 cells were pretreated with or without 40 micromol/L tBHQ for 4 h, PC12 cells were exposed to PQ at the doses of 0, 100, 300 micromol/L for 24 h and 48 h, respectively. The viability of PC12 cells was measured by MTT assay, the apoptosis rates of PC12 cells were detected by flow cytometry (FCM) and the malondialdehyde (MDA) levels of PC12 cells were examine by thiobarbituric acid (TBA) method. RESULTS: When the exposure doses of PQ were 100 and 300 micromol/L for 24 h, the viability of PC12 cells pretreated with tBHQ was significantly higher than that of PC12 cells only exposed to PQ (P < 0.05 or P < 0.01). When the exposure dose of PQ was 100 micromol/L for 48 h, the viability of PC12 cells pretreated with tBHQ was significantly higher than that of PC12 cells only exposed to PQ (P < 0.01). When the exposure doses of PQ were 100 and 300 micromol/L for 24 h, the apoptosis rates and MDA levels of PC12 cells pretreated with tBHQ were significantly lower than those of PC12 cells only exposed to PQ (P < 0.05 or P < 0.01). CONCLUSIONS: tBHQ pretreatment can reduce the cytotoxicity, apoptosis and oxidative stress induced by PQ in PC12 cells.

Ventral tegmental area GABAergic neurons induce anxiety-like behaviors and promote palatable food intake.

The obesity epidemic is a global problem and a great challenge for public health. Overconsumption of food, especially palatable food, is the leading cause of obesity. The precise neural circuits underlying food overconsumption remain unclear and require further characterization. In the present study, we showed that Ca2+ signals of GABAergic neurons within the ventral tegmental area (VTA) increased after the onset of food intake, especially high-fat or high-sugar chow. Optogenetic activation of VTA GABAergic neurons evoked immediate eating of palatable food and significantly increased palatable food intake in satiated mice. Photoinhibition of VTA GABAergic neurons suppressed palatable food intake. Surprisingly, photoactivation of VTA GABAergic neurons suppressed the intake of standard chow in fasted mice, but did not reduce the duration of eating of standard chow. Moreover, we found that photoactivation of these neurons drove a series of anxiety-like behaviors in the open field, elevated plus maze, and marble-burying test. Additionally, we found that VTA GABAergic neurons sent abundant projections to the lateral hypothalamus and photoactivation of GABAergic VTA terminals in the lateral hypothalamus induced overconsumption of palatable food, but not anxiety-like behaviors. Taken together, our results illustrate that GABAergic VTA neurons are a key node in the neural circuitry underlying anxiety-like behavior and over-feeding of palatable food, and that over-excitation of GABAergic VTA neurons may underlie clinical diseases related to anxiety and obesity.

Basal forebrain GABAergic neurons promote arousal and predatory hunting.

Predatory hunting is an important approach for animals to obtain valuable nutrition and energy, which critically depends on heightened arousal. Yet the neural substrates underlying predatory hunting remain largely undefined. Here, we report that basal forebrain (BF) GABAergic neurons play an important role in regulating predatory hunting. Our results showed that BF GABAergic neurons were activated during the prey (cricket)-hunting and food feeding in mice. Optogenetic activation of BF GABAergic neurons evoked immediate predatory-like actions to both artificial and natural preys, significantly reducing the attack latency while increasing the attack probability and the number of killed natural prey (crickets). Similar to the effect of activating the soma of BF GABAergic neurons, photoactivation of their terminals in the ventral tegmental area (VTA) also strongly promotes predatory hunting. Moreover, photoactivation of GABAergic BF - VTA pathway significantly increases the intake of various food in mice. By synchronous recording of electroencephalogram and electromyogram, we showed that photoactivation of GABAergic BF - VTA pathway induces instant arousal and maintains long-term wakefulness. In summary, our results clearly demonstrated that the GABAergic BF is a key neural substrate for predatory hunting, and promotes this behavior through GABAergic BF - VTA pathway.

Glutamatergic lateral hypothalamus promotes defensive behaviors.

The glutamatergic lateral hypothalamus (LH) has been implicated in a variety of behaviors, such as evasion and feeding, while its role in defensive behaviors and relevant neurocircuits remains unclear. Here, we demonstrated that the glutamatergic LH is a critical structure regulating defensive behaviors. Trimethylthiazole (TMT), the odor of mice predator, significantly increased c-Fos expression in the LH. Using fiber photometry technology, we found that TMT exposure increased the activity of LH glutamatergic neurons. Selective activation of LH glutamatergic neurons with optogenetics and chemogenetics promoted a series of defense-related behaviors, including fleeing, avoidance, and hiding, while selective inhibition of LH glutamatergic neurons suppressed the avoidance provoked by TMT. Activation of both the glutamatergic LH terminals in the hypothalamic paraventricular nucleus (PVN) and the glutamatergic projection from the basolateral amygdala (BLA) to the LH elicited defensive behaviors. Finally, by combining the viral-mediated retrograde tracing with anterograde activation, we found that PVN-projecting glutamatergic neurons in the LH were activated by BLA glutamatergic inputs. Taken together, our results illustrate that the glutamatergic LH is a pivotal relay of defensive behaviors and possibly promotes these behaviors through the BLA→LH→PVN pathway.

[Effect of deltamethrin on production of free radical and transcription factor Nrf2 in rats' brain tissue].

OBJECTIVE: To explore the effect of deltamethrin (DM) on production of free radical and transcription factor Nrf2 in rats' brain tissue. METHODS: 8 male rats were randomly assigned to four groups and administered with 1% W/W tertiary butylhydroquinone (tBHQ) or olive oil for 3 days, prior to exposure to DM and then with 12.50 mg or 0mg DM/Kg BW for 5 days. The level of free radical in rats' hippocampus tissue was detected by electron spin resonance (ESR) spectroscopy. 18 male rats were randomly assigned to three groups and administered with i.p. (daily dose was respectively 0, 3.13, 12.50 mg/kg DM) for five days. After treatment, Nrf2 protein levels in the cytoplasmic and nuclear fractions of both cerebral cortex and hippocampus tissue were measured by western blot. RESULTS: The level of free radical in hippocampus tissue of rats administered by DM and pretreatment with tBHQ prior to DM were increased to a 2.45-fold and 2.97-fold of values of control group, respectively (P < 0.05). Nrf2 protein levels in the cytoplasmic fractions of cerebral cortex of both low and high dose group were significantly increased, 1.68- fold and 1.34- fold of values of control group, respectively. Nrf2 protein levels in the nuclear fractions of cerebral cortex of both low and high dose group were increased in a dose- dependent model, 1.51-fold and 2.29-fold of values of control group, respectively (P < 0.01). Nrf2 protein levels in the cytoplasmic fractions of hippocampus tissue of both low and high dose group were increased in a dose- dependent model, 2.26-fold and 3.58-fold of values of control group, respectively. Nrf2 protein levels in the nuclear fractions of hippocampus tissue of both low and high dose group were increased, 2.42-fold and 2.45-fold of values of control group, respectively (P < 0.01). CONCLUSION: The studies in vivo demonstrate that DM treatment could induce free radical production and expression of Nrf2 protein in both cerebral cortex and hippocampus tissue and activate Nrf2.

[Protective effect of tert-butylhydroquinone on PC12 cells from neurotoxicity induced by manganese in vitro].

OBJECTIVE: To investigate the protective effect of the tert-butylhydroquinone (tBHQ) on PC12 cells from neurotoxicity induced by manganese. METHODS: Cytotoxicity of PC12 cells was measured by MTT assay, following the PC12 cells treatment with different concentrations of MnCl2 (300, 600, 900 µmol/L) for 24, 48 or 72 h. PC12 cells were pretreated with 40 µmol/L tBHQ for 12 h, followed by the treatment of 600 micromol/L or 300 µmol/L MnCl2 for 72 h. Cytotoxicity of PC12 cells was measured by MTT assay, and cell apoptosis was examined by the method of Annexin V-FITC/PI in flow cytometry (FCM). RESULTS: The proliferation of PC12 cells treated with 300, 600, 900 µmol/L MnCl2 was suppressed in the dose dependent pattern (P < 0.01). Proliferation of PC12 cells treated with 600 µmol/L MnCl2 was suppressed to 40% of that in control group (P < 0.01), but the proliferation rate of PC12 cell pretreated with 40 µmol/L tBHQ was 180% of that in control group (P < 0.01). Apoptotic rate of PC12 cells treated with 300 micromol/L MnCl2 was higher than the vehicle control group (P < 0.01). Apoptotic rate of 40 µmol/L tBHQ pretreatment followed by 300 µmol/L MnCl2 treatment was lower than that of MnCl2 treatment group (P < 0.01). The inhibition rate of apoptosis was 61%. CONCLUSIONS: Manganese may suppress PC12 cells proliferation and induce apoptosis. tBHQ can reduce PC12 cells proliferation suppressed by manganese and attenuate the apoptosis induced by manganese.

Meteorological Variation Is a Predisposing Factor for Aneurismal Subarachnoid Hemorrhage: A 5-Year Multicenter Study in Fuzhou, China.

OBJECTIVE: The climatic characteristics of aneurysmal subarachnoid hemorrhage (aSAH) have been reported, but consensus has not yet been reached. It is of great significance to elucidate the relationships between meteorological variation and aSAH in regions with specific climate patterns. We analyzed the occurrence of aSAH in the capital city of Fujian Province, China, through a multicenter, 5-year study, and aimed to reveal the meteorological influences on aSAH in the coastal city of eastern Fujian under the subtropical marine monsoon condition. METHODS: A total of 2555 consecutive patients with aSAH in Fuzhou were collected using specialized stroke admission database from January 2013 to December 2017. Meteorological parameters including temperature, atmospheric pressure, and humidity were obtained from China Surface Meteorological Station during the same period. Poisson regression was used to explore the association between meteorological parameters and aSAH to calculate the incidence rate ratios (IRRs) with corresponding 95% confidence intervals (CIs). Generalized additive model analysis further revealed the nonlinear relationships between weather and aSAH. RESULTS: Daily minimum temperature (IRR 0.976, 95% CI 0.958-0.996) and maximum pressure (IRR 1.022, 95% CI 1.001-1.042) were independently correlated with the onset of aSAH. Low temperature (below 16°C) and excessive atmospheric pressure (above 1008 hPa) increased the risk of aSAH. In addition, March in spring and December in winter were the 2 ictus peaks in Fuzhou throughout the year. CONCLUSIONS: Cold and excessive atmospheric pressure are triggers for the occurrence of aSAH; March in spring and December in winter are the predominant onset periods in Fuzhou.

[Effect of deltamethrin on production of reactive oxygen species in PC12 cells].

OBJECTIVE: To investigate the effect of deltamethrin (DM) on production of reactive oxygen species (ROS) of rat pheochromocytoma (PC12) cells and its mechanism. METHODS: PC12 cells were treated with various dose of DM (0, 10 or 100 micromol/L) for 1, 6 or 12 h respectively. Furthermore, PC12 cells were treated with various dose of DM (0, 10 or 100 micromol/L) for 24 or 48 h, respectively. PC12 cells were pre-incubated with 10 mmol/L N-acetyl-L-cysteine (NAC) for 2 h, or with 500 micromol/L DL-Buthionine-[S, R]-Sulfoximine (BSO) for 16 h, or with 40 micromol/L tertiary butylhydroquinone (tBHQ) for 16 h, prior to exposure to DM and then with 10 micromol/L DM for 6 h. After treatment, ROS production in PC12 cells were measured by a molecular probe, 2', 7'-dichlorofluorescein diacetate (DCFH-DA). RESULTS: DM induced a dose-time dependent increase in ROS production (indicated by DCF fluorescence intensity). 10 micromol/L DM treatment for 6 h enhanced DCF fluorescence intensity that reached approximately 2.24 times of values of control group. Furthermore, a pretreatment with NAC, BSO or tBHQ significantly reduced the DM-enhanced DCF fluorescence intensity that reached approximately 22%, 62% or 38% of values of DM treatment, respectively (P < 0.05), indicating that all these pretreatments attenuate ROS production. CONCLUSION: The in vitro studies demonstrate that DM could enhance ROS production, and may be the influential factor for the decreased mercapto level and antioxidative function.

Transcription factor Nrf2 activation by deltamethrin in PC12 cells: Involvement of ROS.

Activation of transcription factor NF-E2-related factor 2 (Nrf2) is a key initiation step in the cellular protection against a broad range of chemical oxidative stresses. To gain insights into dopaminergic cell responses to pesticides, the present study was conducted to examine the effects of deltamethrin (DM), a prototype of widely used pyrithroid pesticides, on the activation and expression of Nrf2 in PC12 rat adrenal pheochromocytoma cells as a dopaminergic cell model. We found, for the first time, that DM enhanced cellular expression of Nrf2 at the transcriptional and protein levels and activated expression of Nrf2-regulated genes in these cells. In addition, DM exposure caused nuclear accumulation of Nrf2 in association with downstream activation of Nrf2-mediated oxidative response genes, such as heme oxygenase-l (HO-1) and gamma-glutamylcysteine synthetase catalytic heavy subunit (GCSh). Furthermore, when cells were pretreated with N-acetyl cysteine (NAC), a scavenger of reactive oxygen species (ROS), DM-induced Nrf2 signaling was suppressed. These results indicate that ROS is the mediator of nuclear Nrf2 accumulation. Taken together, these data clearly show that DM increases Nrf2 expression and activity and that ROS is one of the mediators of this process.

Independent and combined effects of environmental factors and miR-126, miR-143, and miR-145 on the risk of coronary heart disease.

OBJECTIVE: To evaluate the effects of environmental factors and microRNAs (miRNAs) (miR-126, miR-143, and miR-145) on the risk of coronary heart disease (CHD). METHODS: A frequency-matched case-control study (450 patients, 450 controls) was conducted from April 2014 to December 2016 in Fuzhou City, China. Environmental factors were investigated using a self-administered questionnaire, and the expression levels of miR-126, miR-143, and miR-145 were determined by quantitative real-time Polymerase Chain Reaction (PCR) in peripheral blood mononuclear cells. Unconditional logistic regression models were used for statistical evaluation. RESULTS: Alcohol consumption, high-salt diets, high-intensity work, and lack of physical activity were significantly associated with increased CHD risk, whereas light diet was significantly associated with decreased risk. MiR-126, miR-143, and miR-145 were highly expressed in the CHD group compared with the control group. After adjustment for other environmental factors, unconditional logistic regression results revealed that miR-126, miR-143, and depression were the independent risk factors of CHD, and light diet was the independent protective factor of CHD. CONCLUSIONS: Our data suggest that a family history of CHD, anxiety, and alcohol consumption was significantly associated with increased CHD risk, whereas light diet was significantly associated with decreased risk. Furthermore, miR-126 and miR-143 in combination with several risk factors, could play a joint role in the development of CHD. Therefore, it is necessary to manage patients with CHD in all directions and multiple level.

[Time course of gene expression of gamma-glutamylcysteine synthetase subunit and Nrf2 in brain tissues of rats exposed by deltamethrin].

OBJECTIVE: To investigate the time course of mRNA expression of gamma- glutamylcysteine synthetase light (GCSl) and heavy subunit (GCSh), as well as protein expression of both GCSh and NF-E2 related factor 2 (Nrf2) in cerebral cortex and hippocampus in rats exposed at single dose of deltamethrin (DM). METHODS: Wistar male rats were exposed at single dose of DM (12.50 mg/kg bw) with i.p. At various time points of post-exposure, the rats were sacrificed at indicated time, then their cerebral cortex and hippocampus were isolated. The relative amount of mRNA expression of these genes was measured by the method of reverse transcription polymerase chain reaction (RT-PCR). The protein level was detected by the method of immunohistochemistry and image analysis system. RESULTS: (1) At 5 and 48h after DM exposure, GCSh mRNA relative levels in cerebral cortex in rats were significantly decreased to 83.9% and 86.0% of mRNA level of corresponding tissue of control group at Oh, respectively (P < 0.05). At 5, 24 and 48h after DM exposure, transcriptional factors Nrf2 mRNA relative levels were more higher than those of both control and 72 h group and increased to 146.4%, 145.2% and 147.9% of those of control group at Oh,respectively (P < 0.05). (2) At 5 and 48h after DM exposure, GCSh mRNA relative levels in hippocampus were significantly increased to 118.4% and 118.4% of those of control group at 0h, respectively (P < 0.05). At 5h after DM exposure, GCSl mRNA relative levels in hippocampus were more higher than those of control,24h and 48h group and increased to 121.4% of those of control group at Oh (P < 0.05). CONCLUSION: After single dose of DM exposure, there are up-regulation of mRNA expression of both GCSh and GCSl gene in rats hippocampus, down-regulation of mRNA expression of GCSh gene and up-regulation of mRNA expression of Nrf2. gene in rats cerebral cortex under the experimental condition.

[Toxicity and oxidative stress on rats by hexachlorobenzene].

OBJECTIVE: To study the toxicity on rats by hexachlorobenzene (HCB), and to explore the role of oxidative stress in the mechanism of HCB intoxication. METHODS: SD female rats were fed on a powdered diet containing 0.25 per thousand or 2.00 per thousand HCB for 14 days. The content of malondialdehyde (MDA) and the activity of total-superoxide dismutase (T-SOD), catalase (CAT) and glutathione peroxidase (GSH-PX) in cerebral cortex, hippocampus, liver tissue and serum were determined. Eleven biochemical indicators including alkaline phosphatase (ALP) were surveyed. RESULTS: (1) MDA levels in cerebral cortex, hippocampus, liver and serum of the high dosage group rats and that in hippocampus and serum of the low dosage group were significantly higher than that of the control group. (2) The activity of T-SOD was increased in cerebral cortex and hippocampus of the rats in both groups (P < 0.01), but decreased in the serum of the high dosage group (P < 0.01). (3) The activity of CAT was also increased in the hippocampus of rats in the high dosage group. (4) In cerebral cortex and hippocampus of the rats in the high dosage group and in the hippocampus of the rats in the low dosage group, the activity of GSH-PX was significantly higher compared with the control group. However, in liver of both dosage groups, the activity of GSH-PX was decreased (P < 0.01). (5) The activity of serum alkaline phosphatase of both dosage groups was also decreased, but the contents of both serum albumin and total cholesterol were significantly higher than those of the control group (P < 0.01). CONCLUSION: HCB can induce enhanced lipid peroxidation on SD rats, and the oxidative stress plays an important role in the mechanism of neurotoxicity and hepatotoxicity.