Publications by authors named "An Li Wang"

81 Publications

Reductions in tobacco use in naltrexone, relative to buprenorphine-maintained individuals with opioid use disorder: Secondary analysis from the National Drug Abuse Treatment Clinical Trials Network.

J Subst Abuse Treat 2021 May 21;130:108489. Epub 2021 May 21.

Department of Psychiatry, NYU Grossman School of Medicine, One Park Avenue, New York, NY 10016, USA.

Background: Smoking prevalence in individuals with opioid use disorder (OUD) is over 80%. Research suggests that opioid use significantly increases smoking, which could account for the strikingly low smoking-cessation rates observed in both methadone- and buprenorphine-maintained patients, even with the use of first-line smoking-cessation interventions. If opioids present a barrier to smoking-cessation, then better smoking outcomes should be observed in OUD patients treated with extended-release naltrexone (XR-NTX, an opioid antagonist) compared to those receiving buprenorphine (BUP-NX, a partial opioid agonist).

Methods: The current study is a secondary analysis of a 24-week, multi-site, open-label, randomized clinical trial conducted within the National Drug Abuse Treatment Clinical Trials Network comparing the effectiveness of XR-NTX vs. BUP-NX for adults with OUD. Longitudinal mixed effects models were used to determine if there was a significant reduction in cigarette use among daily smokers successfully inducted to treatment (n = 373) and a subset of those who completed treatment (n = 169).

Results: Among daily smokers inducted onto OUD medication, those in the XR-NTX group smoked fewer cigarettes per day (M = 11.36, SE = 0.62) relative to smokers in the BUP-NX group (M = 13.33, SE = 0.58) across all study visits, (b (SE) = -1.97 (0.55), p < .01). Results were similar for the treatment completers.

Conclusions: OUD patients treated with XR-NTX reduced cigarette use more than those treated with BUP-NX, suggesting that XR-NTX in combination with other smoking cessation interventions might be a better choice for OUD smokers interested in reducing their tobacco use.
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http://dx.doi.org/10.1016/j.jsat.2021.108489DOI Listing
May 2021

Moderate prenatal ethanol exposure leads to attention deficits in both male and female rats.

Alcohol Clin Exp Res 2021 05 16;45(5):1122-1135. Epub 2021 Apr 16.

Department of Pharmacology and Toxicology, Jacob School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.

Background: Attention deficits caused by prenatal ethanol (EtOH) exposure (PE) are a prevalent condition in fetal alcohol spectrum disorders (FASDs). Importantly, the deficits are observed in individuals with FASD who have normal IQs and show no dysmorphic facial features caused by heavy PE. These observations suggest that even moderate PE could lead to attention deficits. This possibility was investigated in the present study using a rat model.

Methods: Pregnant Sprague Dawley rats were administered EtOH (3 g/kg/day) or vehicle via intragastric gavage on gestational days 8 to 20. The blood EtOH concentration (BEC) in EtOH-treated rats was 87.7 ± 1.2 mg/dl (1 h after the gavage), similar to the BECs reported in other moderate PE studies in rodents. Moderate PE did not produce teratogenic effects on birthweight or litter size. The adult offspring underwent a 2-choice reaction time task.

Results: Moderate PE led to augmented action impulsivity in both sexes, indicated by more rapid response initiation and more premature responses. Deficits were more marked in males than in females. No greater lapses of attention, assessed by incorrect or relatively slow responses, were observed in rats of either sex with moderate PE. In addition, no deficits in learning or motor function were detected after moderate PE. Interestingly, rats with moderate PE completed more trials than controls.

Conclusions: Our results confirm that moderate PE leads to attention deficits in both sexes, which is demonstrated by greater action impulsivity, but not more lapses of attention. This effect differs from that of heavy PE, as shown in our previous study, which is manifested as impaired action impulsivity and lapses of attention in both sexes.
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http://dx.doi.org/10.1111/acer.14599DOI Listing
May 2021

Mental health-related stigma and attitudes toward patient care among providers of mental health services in a rural Chinese county.

Int J Soc Psychiatry 2021 Feb 7:20764021992807. Epub 2021 Feb 7.

School of Social Policy & Practice, University of Pennsylvania, USA.

Background And Aims: The increasing prevalence of mental illness and low treatment rate presents a pressing public health issue in China. Pervasive stigma is a significant barrier to mental health recovery and community inclusion. In particular, stigmatizing or supportive attitudes held by healthcare providers could either perpetuate or mitigate self-stigma of people with mental illness. Moreover, mental health resources are unevenly distributed in China, with most of them concentrated in urban centers and provincial capitals. This study explores healthcare providers' attitudes toward mental illness and the challenges they faced at work in a rural Chinese county.

Method: Four focus groups were conducted with 36 healthcare providers from a three-tier mental healthcare system in a rural county in southwestern China. Focus group discussions were recorded and transcribed verbatim. The team employed a conventional content analysis approach for data analysis. All transcripts were double-coded by three bilingual team members who are native Chinese speakers. Coding discrepancies were resolved by consensus.

Results: Healthcare providers recruited from the county, township, and village levels varied in educational background, professional qualification, and experience of working with people with mental illness. Five thematic categories identified across four groups include (1) barriers to mental healthcare delivery, (2) keys to mental health recovery, (3) providers' attitudes toward providing care, (4) providers' perception toward patients and family members, and (5) providers' perception of training needs.

Conclusions: This is a unique study that included healthcare providers from a three-tier healthcare system. Findings signal the importance of understanding healthcare practitioners' experiences and views to inform the design of training initiatives in rural or low-resource communities.
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http://dx.doi.org/10.1177/0020764021992807DOI Listing
February 2021

The role of withdrawal in mesocorticolimbic drug cue reactivity in opioid use disorder.

Addict Biol 2021 Jul 23;26(4):e12977. Epub 2020 Oct 23.

Center for Studies of Addiction, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

Opioid use disorder (OUD) is characterized by heightened cognitive, physiological, and neural responses to opioid-related cues that are mediated by mesocorticolimbic brain pathways. Craving and withdrawal are key symptoms of addiction that persist during physiological abstinence. The present study evaluated the relationship between the brain response to drug cues in OUD and baseline levels of craving and withdrawal. We used functional magnetic resonance imaging (fMRI) to examine brain responses to opioid-related pictures and control pictures in 29 OUD patients. Baseline measures of drug use severity, opioid craving, and withdrawal symptoms were assessed prior to cue exposure and correlated with subsequent brain responses to drug cues. Mediation analysis was conducted to test the indirect effect of drug use severity on brain cue reactivity through craving and withdrawal symptoms. We found that baseline drug use severity and opioid withdrawal symptoms, but not craving, were positively associated with the neural response to drug cues in the nucleus accumbens, orbitofrontal cortex, and amygdala. Withdrawal, but not craving, mediated the effect of drug use severity on the nucleus accumbens' response to drug cues. We did not find similar effects for the neural responses to stimuli unrelated to drugs. Our findings emphasize the central role of withdrawal symptoms as the mediator between the clinical severity of OUD and the brain correlates of sensitization to opioid-related cues. They suggest that in OUD, baseline withdrawal symptoms signal a high vulnerability to drug cues.
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http://dx.doi.org/10.1111/adb.12977DOI Listing
July 2021

Neutral Sphingomyelinase is an Affective Valence-Dependent Regulator of Learning and Memory.

Cereb Cortex 2021 Jan;31(2):1316-1333

Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen 91054, Germany.

Sphingolipids and enzymes of the sphingolipid rheostat determine synaptic appearance and signaling in the brain, but sphingolipid contribution to normal behavioral plasticity is little understood. Here we asked how the sphingolipid rheostat contributes to learning and memory of various dimensions. We investigated the role of these lipids in the mechanisms of two different types of memory, such as appetitively and aversively motivated memory, which are considered to be mediated by different neural mechanisms. We found an association between superior performance in short- and long-term appetitively motivated learning and regionally enhanced neutral sphingomyelinase (NSM) activity. An opposite interaction was observed in an aversively motivated task. A valence-dissociating role of NSM in learning was confirmed in mice with genetically reduced NSM activity. This role may be mediated by the NSM control of N-methyl-d-aspartate receptor subunit expression. In a translational approach, we confirmed a positive association of serum NSM activity with long-term appetitively motivated memory in nonhuman primates and in healthy humans. Altogether, these data suggest a new sphingolipid mechanism of de-novo learning and memory, which is based on NSM activity.
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http://dx.doi.org/10.1093/cercor/bhaa298DOI Listing
January 2021

Neutral ceramidase is a marker for cognitive performance in rats and monkeys.

Pharmacol Rep 2021 Feb 16;73(1):73-84. Epub 2020 Sep 16.

Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany.

Background: Ceramides are lipid molecules determining cell integrity and intercellular signaling, and thus, involved in the pathogenesis of several psychiatric and neurodegenerative disorders. However, little is known about the role of particular enzymes of the ceramide metabolism in the mechanisms of normal behavioral plasticity. Here, we studied the contribution of neutral ceramidase (NC), one of the main enzymes mediating ceramide degradation, in the mechanisms of learning and memory in rats and non-human primates.

Methods: Naïve Wistar rats and black tufted-ear marmosets (Callithrix penicillata) were tested in several tests for short- and long-term memory and then divided into groups with various memory performance. The activities of NC and acid ceramidase (AC) were measured in these animals. Additionally, anxiety and depression-like behavior and brain levels of monoamines were assessed in the rats.

Results: We observed a predictive role of NC activity in the blood serum for superior performance of long-term object memory tasks in both species. A brain area analysis suggested that high NC activity in the ventral mesencephalon (VM) predicts better short-term memory performance in rats. High NC activity in the VM was also associated with worse long-term object memory, which might be mediated by an enhanced depression-like state and a monoaminergic imbalance.

Conclusions: Altogether, these data suggest a role for NC in short- and long-term memory of various mammalian species. Serum activity of NC may possess a predictive role in the assessing the performance of certain types of memory.
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http://dx.doi.org/10.1007/s43440-020-00159-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862079PMC
February 2021

Multi-View Cluster Analysis with Incomplete Data to Understand Treatment Effects.

Inf Sci (N Y) 2019 Aug 22;494:278-293. Epub 2019 Apr 22.

Department of Computer Science and Engineering, University of Connecticut, Storrs, CT, USA.

Multi-view cluster analysis, as a popular granular computing method, aims to partition sample subjects into consistent clusters across different views in which the subjects are characterized. Frequently, data entries can be missing from some of the views. The latest multi-view co-clustering methods cannot effectively deal with incomplete data, especially when there are mixed patterns of missing values. We propose an enhanced formulation for a family of multi-view co-clustering methods to cope with the missing data problem by introducing an indicator matrix whose elements indicate which data entries are observed and assessing cluster validity only on observed entries. In comparison with the simple strategy of removing subjects with missing values, our approach can use all available data in cluster analysis. In comparison with common methods that impute missing data in order to use regular multi-view analytics, our approach is less sensitive to imputation uncertainty. In comparison with other state-of-the-art multi-view incomplete clustering methods, our approach is sensible in the cases of missing any value in a view or missing the entire view, the most common scenario in practice. We first validated the proposed strategy in simulations, and then applied it to a treatment study of heroin dependence which would have been impossible with previous methods due to a number of missing-data patterns. Patients in a treatment study were naturally assessed in different feature spaces such as in the pre-, during-and post-treatment time windows. Our algorithm was able to identify subgroups where patients in each group showed similarities in all of the three time windows, thus leading to the recognition of pre-treatment (baseline) features predictive of post-treatment outcomes.
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http://dx.doi.org/10.1016/j.ins.2019.04.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455020PMC
August 2019

Reduced cigarette smoking during injectable extended-release naltrexone treatment for opioid use disorder.

Am J Drug Alcohol Abuse 2020 07 7;46(4):472-477. Epub 2020 May 7.

Center for Studies of Addiction, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA, USA.

Background: The prevalence of tobacco cigarette smoking in the US has declined to approximately 15%, yet, it remains over 90% among individuals with opioid use disorder regardless of whether they are currently using opioids illicitly or as opioid substitution therapy. This disparity raises the question of whether opioids facilitate smoking among individuals with opioid use disorder and whether opioid antagonists may reduce it.

Objectives: Determine whether injectable extended-release naltrexone (XR-NTX) treatment of opioid use disorder patients is associated with a spontaneous smoking reduction. We hypothesized that treatment with XR-NTX for would lead to a reduction in smoking in tobacco cigarette smokers with opioid use disorder.

Methods: We analyzed data from 64 tobacco cigarette smokers (38% female) with opioid use disorder who were induced on XR-NTX for prevention of relapse to opioids. The number of cigarettes smoked per day and opioid-related craving and withdrawal were assessed at baseline and during treatment.

Results: Smoking was reduced from 14.4 ± 1.0 to 9.8 ± 1.0(p < 0.001) cigarettes per day after one month and 8.6 ± 1.1 cigarettes per day after two months of treatment. Daily cigarette consumption was positively correlated with the pre-treatment frequency of opioid use and opioid-related craving during the XR-NTX treatment.

Conclusions: XR-NTX treatment in smokers with opioid use disorder was associated with a 29% decline in daily cigarette consumption. Together with prior evidence of increased smoking during opioid agonist therapy, our finding suggests a pharmacodynamic interaction between nicotine and opioid systems that could influence treatment choices in this population. Our findings merit confirmation in a prospective controlled study. (NCT02324725 and NCT01587196).
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http://dx.doi.org/10.1080/00952990.2020.1741001DOI Listing
July 2020

Connectivity between visual and auditory cortices mediates the influence of argument strength on the effectiveness of smoking-cessation videos among smokers low in sensation seeking.

Psychol Res Behav Manag 2019 18;12:531-542. Epub 2019 Jul 18.

Center for Studies of Addiction, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.

Purpose: Argument strength (AS) is a validated measure of persuasiveness that has been identified as one of the key variables determining the effectiveness of video ads. Smoking-cessation videos with high AS are more effective at reducing smoking behavior than videos with low AS. The neural processes that mediate the effects of AS on subsequent smoking have not been identified. In the present study, we tested whether the efficacy of high-AS smoking-cessation videos is determined by the level of integration of visual and auditory (ie, multisensory) processes. In addition, we tested differences in sensation seeking, which is repeatedly associated with smokers' sensitivity to cessation interventions.

Patients And Methods: Using functional magnetic resonance imaging (fMRI), we recorded the brain response of 66 smokers randomly assigned to view either 16 high-AS or 16 low-AS smoking-cessation videos. Multisensory processing was assessed by the functional connectivity between brain regions that encoded visual and auditory information in the videos. Smoking behavior was indexed by the urine level of cotinine, a nicotine metabolite, immediately before and approximately 30 days after the fMRI session.

Results: We found a significant moderated mediation effect, such that the connectivity between visual and auditory cortices mediated the effect of AS on subsequent smoking, but only for smokers lower in sensation seeking. The prediction performance of the model was confirmed by leave-one-out cross-validation.

Conclusion: Our study suggests that audiovisual integration underlies the greater efficacy of high- vs low-AS smoking-cessation videos for individuals lower in sensation seeking. High-sensation-seeking smokers may be responsive to other characteristics of smoking-cessation videos.
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http://dx.doi.org/10.2147/PRBM.S183394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6645608PMC
July 2019

Brain Responses to Anti-Smoking Health Warnings In Youth.

Curr Addict Rep 2018 Sep 19;5(3):372-378. Epub 2018 Jul 19.

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029 USA.

Purpose Of The Review: Adolescents and young adults are a critical target for smoking prevention efforts. Health education is a key approach to these efforts, yet little is known about how adolescents and young adults process health information. One novel approach to understanding the neurobiological mechanisms of cognitive processing of public health communications is to use neuroimaging techniques to map the brain regions involved and make inferences about the neural systems engaged in the processing of health information. We reviewed recent studies that employed functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) to examine the brain responses of adolescents and young adults to anti-smoking health messages and videos.

Findings: This narrative literature review found that the medial prefrontal cortex, amygdala, and hippocampus were the brain regions most commonly engaged in response to health warnings. Developmental factors modulate the relationship between brain regions, regulated emotional reaction, and frontal regions that are responsible for decision making.

Summary: Research that integrates neurophysiology and behavior to study adolescent and young adult neurocognitive responses to health messaging is an important tool for identifying optimal methods to communicate the health hazards of smoking to this vulnerable population.
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http://dx.doi.org/10.1007/s40429-018-0221-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687325PMC
September 2018

Disrupted-in-Schizophrenia 1 (DISC1) Overexpression and Juvenile Immune Activation Cause Sex-Specific Schizophrenia-Related Psychopathology in Rats.

Front Psychiatry 2019 9;10:222. Epub 2019 Apr 9.

Department of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.

Synaptic pruning is a critical refinement step during neurodevelopment, and schizophrenia has been associated with overpruning of cortical dendritic spines. Both human studies and animal models implicate disrupted-in-schizophrenia 1 (DISC1) gene as a strong susceptibility factor for schizophrenia. Accumulating evidence supports the involvement of DISC1 protein in the modulation of synaptic elimination during critical periods of neurodevelopment and of dopamine D2-receptor-mediated signaling during adulthood. In many species, synaptic pruning occurs during juvenile and adolescent periods and is mediated by microglia, which can be over-activated by an immune challenge, giving rise to overpruning. Therefore, we sought to investigate possible interactions between a transgenic DISC1 model (tgDISC1) and juvenile immune activation (JIA) by the bacterial cell wall endotoxin lipopolysaccharide on the induction of schizophrenia-related behavioral and neurochemical disruptions in adult female and male rats. We examined possible behavioral aberrations along three major symptom dimensions of schizophrenia including psychosis, social and emotional disruptions, and cognitive impairments. We detected significant gene-environment interactions in the amphetamine-induced locomotion in female animals and in the amphetamine-induced anxiety in male animals. Surprisingly, gene-environment interactions improved social memory in both male and female animals. JIA alone disrupted spatial memory and recognition memory, but only in male animals. DISC1 overexpression alone induced an improvement in sensorimotor gating, but only in female animals. Our neurochemical analyses detected sex- and manipulation-dependent changes in the postmortem monoamine content of animals. Taken together, we here report sex-specific effects of environment and genotype as well as their interaction on behavioral phenotypes and neurochemical profiles relevant for schizophrenia.
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http://dx.doi.org/10.3389/fpsyt.2019.00222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465888PMC
April 2019

Anxiogenic-like behavior and deficient attention/working memory in rats expressing the human DISC1 gene.

Pharmacol Biochem Behav 2019 04 16;179:73-79. Epub 2019 Feb 16.

Center for Behavioral Neuroscience, Institute of Experimental Psychology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. Electronic address:

In humans, mutations in the Disrupted-in-schizophrenia 1 (DISC1) gene have been related to psychiatric disorders, including symptoms of abnormal cognitive and emotional behaviors. In our previous studies, overexpression of the human DISC1 gene in rats resulted in schizophrenia-like phenotypes showing deficits in motor learning, impaired cognitive function and dysfunctions of the dopamine system. Here we asked, whether the DISC1 overexpression affects locomotor activity in the open field (OF), anxiety in the elevated plus-maze (EPM), depression-related behavior in the forced swim test (FST), and attention-like/short-term working-memory in the spontaneous alternation behavior (SAB) in the T-maze in transgenic DISC1 (tgDISC1) rats and littermate controls (WT). TgDISC1 rats showed enhanced anxiety behavior in the EPM and an impairment in attention-like/short-term working-memory in the SAB. However, tgDISC1 animals showed no locomotor impairments or depression-like behavior in the OF and FST. These results suggest that DISC1 overexpression leads to higher anxiety level and an attention-like/working-memory deficit. These findings may expand the causal role of DISC1 in its contribution to multiple symptom dimensions of psychiatric disorders.
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http://dx.doi.org/10.1016/j.pbb.2019.02.005DOI Listing
April 2019

Behavioral and Accumbal Responses During an Affective Go/No-Go Task Predict Adherence to Injectable Naltrexone Treatment in Opioid Use Disorder.

Int J Neuropsychopharmacol 2019 03;22(3):180-185

Annenberg Public Policy Center, University of Pennsylvania, Philadelphia, PA.

Adherence is a major factor in the effectiveness of the injectable extended-release naltrexone as a relapse prevention treatment in opioid use disorder. We examined the value of a variant of the Go/No-go paradigm in predicting extended-release naltrexone adherence in 27 detoxified opioid use disorder patients who were offered up to 3 monthly extended-release naltrexone injections. Before extended-release naltrexone, participants performed a Go/No-go task that comprised positively valenced Go trials and negatively valenced No-go trials during a functional magnetic resonance imaging scan. Errors of commission and neural responses to the No-go vs Go trials were independent variables. Adherence, operationalized as the completion of all 3 extended-release naltrexone injections, was the outcome variable. Fewer errors of commission and greater left accumbal response during the No-go vs Go trials predicted better adherence. These findings support the clinical potential of the behavioral and neurophysiological correlates of response inhibition in the prediction of extended-release naltrexone treatment outcomes in opioid use disorder.
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http://dx.doi.org/10.1093/ijnp/pyz002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403086PMC
March 2019

cDNA cloning and expression analysis of glutaredoxin (Grx) 2 in the Pacific white shrimp Litopenaeus vannamei.

Fish Shellfish Immunol 2019 Mar 8;86:662-671. Epub 2018 Dec 8.

Hainan Provincial Key Laboratory for Functional Components Research and Utilization of Marine Bio-resources, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou, 571101, People's Republic of China. Electronic address:

Glutaredoxin (Grx) is a class molecule oxidoreductase, which can regulate the redox state of proteins and plays a key role in antioxidant defense. However, the informations of Grx cDNA sequences and their functions are lack in decapod crustacea. In the present study, the cDNA of LvGrx 2 was cloned from the Pacific white shrimp, Litopenaeus vannamei. The open reading frame (ORF) of LvGrx 2 was 360 bp, which encoded a polypeptide of 119 amino acids. The molecular mass of the predicted protein is 12.87 kDa with an estimated pI of 8.22. Sequence alignment showed that the amino acid sequence of LvGrx 2 shares 59%, 59% and 58% identity with that of the coelacanth Latimeria chalumnae, the plateau frog Nanorana parkeri and the half-smooth tongue sole Cynoglossus semilaevis, respectively. Quantitative real-time PCR analysis revealed that LvGrx 2 were detected in a wide range of tissues, with highest expression in gill, hepatopancrea and intestine, and weakest expression in muscle. The expression responses of LvGrx 2 were analyzed in hepatopancrea and gill after ammonia-N stress or lipopolysaccharide (LPS) injection. During ammonia-N exposure, the LvGrx 2 transcriptions in hepatopancrea and gill significantly up-regulated, and the peak value appeared after 12 h and 24 h exposure respectively. After LPS injection, expression levels of LvGrx 2 in hepatopancrea obviously increased in the early and late stages, while LvGrx 2 transcription in gill sharply up-regulated in the middle period. These results suggest that LvGrx 2 may play a vital role in shrimp defense system against environmental stress and pathogen infection. RNA interference experiment was designed to further probe roles of LvGrx 2 during ammonia-N exposure. Ammonia-N induced obvious improvement in expression levels of LvGrx 2, LvGrx 3, GPx, GST and Trx, accompanied by increases of protein carbonyl and malondialdehyde (MDA) contents. However, transcription of GPx and GST were much weaker in LvGrx 2 interfered-shrimp, and oxidative damage in both lipid and protein were more serious. These results further suggest that LvGrx 2 in shrimp participates in oxidative defence and regulation of antioxidant system.
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http://dx.doi.org/10.1016/j.fsi.2018.12.011DOI Listing
March 2019

Effects of extended-release naltrexone on the brain response to drug-related stimuli in patients with opioid use disorder.

J Psychiatry Neurosci 2018 07;43(4):254-261

From the Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa. (Shi, Wang, Jagannathan, Fairchild, O'Brien, Childress, Langleben); the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY (Wang); the Annenberg Public Policy Center, University of Pennsylvania, Philadelphia, Pa. (Langleben); and the Corporal Michael J. Crescenz Veterans Administration Medical Center, Philadelphia, Pa. (Langleben).

Background: Heightened response to drug-related cues is a hallmark of addiction. Extended-release naltrexone (XR-NTX) is a US Food and Drug Administration-approved pharmacotherapy for relapse prevention in patients with opioid use disorder (OUD). In these patients, XR-NTX has been shown to reduce brain responses to opioid-related visual stimuli. To assess the biomarker potential of this phenomenon, it is necessary to determine whether this effect is limited to opioid-related stimuli and whether it is associated with key OUD symptoms.

Methods: Using functional MRI (fMRI), we measured the brain responses to opioid-related and control (i.e., sexual and aversive) images in detoxified patients with OUD before, during and after XR-NTX treatment. Craving and withdrawal severity were evaluated using clinician- and self-administered instruments during each session.

Results: We included 24 patients with OUD in our analysis. During XR-NTX treatment, we found reduced responses to opioid-related stimuli in the nucleus accumbens (NAcc) and medial orbitofrontal cortex (mOFC). The reduction in mOFC response was specific to the opioid-related stimuli. The reduced NAcc and mOFC opioid cue reactivity was correlated with reduction in clinician-assessed and self-reported withdrawal symptoms, respectively.

Limitations: The study was not placebo-controlled owing to ethical, safety and feasibility concerns.

Conclusion: Extended-release naltrexone reduces the NAcc and mOFC cue reactivity in patients with OUD. This effect is specific to opioid-related stimuli in the mOFC only. The reduction in neural response to opioid-related stimuli is more robust in patients with greater decline in withdrawal severity. Our results support the clinical utility of mesocorticolimbic cue reactivity in monitoring the XR-NTX treatment outcomes and highlight the link between opioid withdrawal symptomatology and neural opioid cue reactivity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019353PMC
July 2018

A Grading Scale for Pial Collaterals in Middle Cerebral Artery Total Occlusion Based on Time-of-flight MR Angiography Source Images.

Magn Reson Med Sci 2019 Jan 31;18(1):62-69. Epub 2018 May 31.

Department of Neurology, The First Affiliated Hospital, College of Medicine, Zhejiang University.

Purpose: To verify whether a new grading based on time-of-flight magnetic resonance angiography source images (TOF-MRAsi) can reflect the abundance of pial collaterals, in patients with total occlusion of M1 segment of middle cerebral artery in the chronic stage.

Methods: In this single-center retrospective study, consecutive patients with total occlusion of M1 segment of middle cerebral artery, with both magnetic resonances angiography and digital subtraction angiography image were included. Time-of-flight magnetic resonance angiography source images were evaluated in a blinded fashion for pial collaterals (PCs) that were graded on a four-point scale. Good and poor PCs were defined as TOF-MRAsis grade <2 and ≥2, respectively. Receiver operating characteristic curve analysis was done to calculate the area under curve, sensitivity, and specificity.

Results: A total of 26 patients were included. The inter-reader agreement for time TOF-MRAsi and digital subtraction angiography images were 0.930 and 0.843, respectively. Compared with digital subtraction angiography grading, the area under curve of pial collateral grading based on TOF-MRAsi was 0.830 (0.636-1.000; P = 0.006). The sensitivity and specificity were 0.700 and 0.933, respectively. The modified Rankin Scale at follow-up was lower in patients with good PCs than in those with poor PCs (0[0, 1] vs. 1[1, 3], P = 0.055), although statistical significance was not reached.

Conclusion: The grading scale based on TOF-MRAsi could be a new empirical approach for pial collateral evaluation. The clinical use of the proposed approach for identifying patients with total occlusion of middle cerebral artery with a high risk of poor outcome requires evaluation in further studies.
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http://dx.doi.org/10.2463/mrms.mp.2018-0001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326771PMC
January 2019

[Aerobic exercise improves spermatogenesis of male rats: Results of iTRAQ-based proteomic analysis of the testis tissue].

Zhonghua Nan Ke Xue 2017 Sep;23(9):776-781

Department of Sport Rehabilitation, Beijing Sport University, Beijing 100083, China.

Objective: To investigate the effect of aerobic exercise on the spermatogenic function of male rats and screen out differentially expressed proteins related to spermatonesis-regulation by proteomic analysis.

Methods: We randomly divided 24 SD male rats into groups A (non-exercise control), B (exercise), and C (weight-bearing exercise), those in the latter two groups made to swim for 60 minutes a day and those in group C bearing a load 3% of the body weight, both 6 times a week for 9 weeks. At 24 hours after the last exercise, we obtained the sperm count, measured the levels of such serum reproductive hormones as testosterone (T), luteotrophic hormone (LH), follicle-stimulating hormone (FSH), and gonadotrophin-releasing hormone (GnRH), and employed isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis of the testicular tissue.

Results: Compared with group A, group C showed significant increases in sperm concentration ([2.12 ± 0.43] vs [3.54 ± 0.52] ×10⁶/ml, P <0.01) and the levels of serum LH ([35.99 ± 2.90] vs [38.96 ± 1.34] IU/L, P <0.01) and T ([19.99 ± 0.25] vs [21.36 ± 0.53] nmol/L, P <0.01), but no statistically significant differences in GnRH ([623.95 ± 41.44] vs [641.82 ± 42.78] ng/L, P >0.05) and FSH ([20.49 ± 2.44] vs [22.29 ± 2.31] IU/L, P >0.05). No significant changes were observed in sperm concentration or reproductive hormone levels in group B as compared with A. Group B exhibited obviously more mature sperm and cell layers in the seminiferous epithelium than group A. A total of 47 differentially expressed proteins were identified, of which 37 were up-regulated and the other 10 down-regulated. In addition, another 5 significantly differentially expressed proteins closely related to reproductive function were identified, including up-regulated Anx A1, GPX3, Rimbp3, and Dpy19l2 and down-regulated CYP17. Enrichment analysis showed that the differentially expressed proteins were mainly involved in extracellular matrix-receptor interaction, protein digestion and absorption, and focal adhesion pathways.

Conclusions: Proper-intensity exercise can improve the spermatogenic function of rats. Aerobic exercise promotes spermatogenesis mainly by up-regulating the expressions of the proteins related to the production and differentiation of spermatozoa.
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September 2017

Emotional salience of the image component facilitates recall of the text of cigarette warning labels.

Eur J Public Health 2019 02;29(1):153-158

Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Background: Graphic warning labels (GWLs) on cigarette packages, that combine textual warnings with emotionally salient images depicting the adverse health consequences of smoking, have been adopted in most European countries. In the US, the courts deemed the evidence justifying the inclusion of emotionally salient images in GWLs insufficient and put the implementation on hold. We conducted a controlled experimental study examining the effect of emotional salience of GWL's images on the recall of their text component.

Methods: Seventy-three non-treatment-seeking daily smokers received cigarette packs carrying GWLs for a period of 4 weeks. Participants were randomly assigned to receive packs with GWLs previously rated as eliciting high or low level of emotional reaction (ER). The two conditions differed in respect to images but used the same textual warning statements. Participants' recognition of GWL images and statements were tested separately at baseline and again after the 4-week repetitive exposure.

Results: Textual warning statements were recognized more accurately when paired with high ER images than when paired with low ER images, both at baseline and after daily exposure to GWLs over a 4-week period.

Conclusion: The results suggest that emotional salience of GWLs facilitates cognitive processing of the textual warnings, resulting in better remembering of the information about the health hazards of smoking. Thus, high emotional salience of the pictorial component of GWLs is essential for their overall effectiveness.
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http://dx.doi.org/10.1093/eurpub/cky059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345145PMC
February 2019

The protective effects of taurine on oxidative stress, cytoplasmic free-Ca and apoptosis of pufferfish (Takifugu obscurus) under low temperature stress.

Fish Shellfish Immunol 2018 Jun 12;77:457-464. Epub 2018 Apr 12.

Key Laboratory of Ecology and Environmental Science of Guangdong Higher Education Institutes, Guangdong Provincial Key Laboratory for Healthy and Safe Aquaculture, School of Life Science, South China Normal University, Guangzhou 510631, PR China. Electronic address:

The present study was aimed to investigate the low temperature toxicity and its protection by taurine in pufferfish. The experimental basal diets supplemented with taurine at the rates of 250 (control), 550, 850, 1140, 1430, 1740 mg kg were fed to fish for 8 weeks. The results showed that fish fed diet with taurine had significantly improved weight gain and specific growth rate. After the feeding trial, the fish were then exposed to low temperature stress. The results showed that low temperature stress could induce reactive oxygen species (ROS) generation, disturb the cytoplasm Ca homeostasis, and lead to oxidative stress and apoptosis. Compared with the control group, dietary taurine supplementation groups increased antioxidant enzyme genes such as manganese superoxide dismutase (Mn-SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT), heat shock proteins (HSP70) and complement C3 (C3) mRNA levels under low temperature stress. Meanwhile, dietary taurine supplementation groups reduced ROS generation, and stabilized the cytoplasm Ca under low temperature stress. Furthermore, dietary taurine supplementation groups reduced apoptosis via decreasing caspase-3 activity. This is the first report to demonstrate the mechanisms of taurine against low temperature stress in fish.
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http://dx.doi.org/10.1016/j.fsi.2018.04.022DOI Listing
June 2018

Effects of extended-release naltrexone on the brain response to drug-related stimuli in patients with opioid use disorder.

J Psychiatry Neurosci 2018 Feb 23;43(3):170036. Epub 2018 Feb 23.

From the Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa. (Shi, Wang, Jagannathan, Fairchild, O'Brien, Childress, Langleben); the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY (Wang); the Annenberg Public Policy Center, University of Pennsylvania, Philadelphia, Pa. (Langleben); and the Corporal Michael J. Crescenz Veterans Administration Medical Center, Philadelphia, Pa. (Langleben).

Background: Heightened response to drug-related cues is a hallmark of addiction. Extended-release naltrexone (XR-NTX) is a US Food and Drug Administration-approved pharmacotherapy for relapse prevention in patients with opioid use disorder (OUD). In these patients, XR-NTX has been shown to reduce brain responses to opioid-related visual stimuli. To assess the biomarker potential of this phenomenon, it is necessary to determine whether this effect is limited to opioid-related stimuli and whether it is associated with key OUD symptoms.

Methods: Using functional MRI (fMRI), we measured the brain responses to opioid-related and control (i.e., sexual and aversive) images in detoxified patients with OUD before, during and after XR-NTX treatment. Craving and withdrawal severity were evaluated using clinician- and self-administered instruments during each session.

Results: We included 24 patients with OUD in our analysis. During XR-NTX treatment, we found reduced responses to opioid-related stimuli in the nucleus accumbens (NAcc) and medial orbitofrontal cortex (mOFC). The reduction in mOFC response was specific to the opioid-related stimuli. The reduced NAcc and mOFC opioid cue reactivity was correlated with reduction in clinician-assessed and self-reported withdrawal symptoms, respectively.

Limitations: The study was not placebo-controlled owing to ethical, safety and feasibility concerns.

Conclusion: Extended-release naltrexone reduces the NAcc and mOFC cue reactivity in patients with OUD. This effect is specific to opioid-related stimuli in the mOFC only. The reduction in neural response to opioid-related stimuli is more robust in patients with greater decline in withdrawal severity. Our results support the clinical utility of mesocorticolimbic cue reactivity in monitoring the XR-NTX treatment outcomes and highlight the link between opioid withdrawal symptomatology and neural opioid cue reactivity.
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http://dx.doi.org/10.1503/jpn.170036DOI Listing
February 2018

Quantitative Proteomics of Synaptosomal Fractions in a Rat Overexpressing Human DISC1 Gene Indicates Profound Synaptic Dysregulation in the Dorsal Striatum.

Front Mol Neurosci 2018 6;11:26. Epub 2018 Feb 6.

Department of Neuroproteomics, Paracelsus Private Medical University, Salzburg, Austria.

Disrupted-in-schizophrenia 1 (DISC1) is a key protein involved in behavioral processes and various mental disorders, including schizophrenia and major depression. A transgenic rat overexpressing non-mutant human DISC1, modeling aberrant proteostasis of the DISC1 protein, displays behavioral, biochemical and anatomical deficits consistent with aspects of mental disorders, including changes in the dorsal striatum, an anatomical region critical in the development of behavioral disorders. Herein, dorsal striatum of 10 transgenic DISC1 (tgDISC1) and 10 wild type (WT) littermate control rats was used for synaptosomal preparations and for performing liquid chromatography-tandem mass spectrometry (LC-MS)-based quantitative proteomics, using isobaric labeling (TMT10plex). Functional enrichment analysis was generated from proteins with level changes. The increase in DISC1 expression leads to changes in proteins and synaptic-associated processes including membrane trafficking, ion transport, synaptic organization and neurodevelopment. Canonical pathway analysis assigned proteins with level changes to actin cytoskeleton, Gαq, Rho family GTPase and Rho GDI, axonal guidance, ephrin receptor and dopamine-DARPP32 feedback in cAMP signaling. DISC1-regulated proteins proposed in the current study are also highly associated with neurodevelopmental and mental disorders. Bioinformatics analyses from the current study predicted that the following biological processes may be activated by overexpression of DISC1, i.e., regulation of cell quantities, neuronal and axonal extension and long term potentiation. Our findings demonstrate that the effects of overexpression of non-mutant DISC1 or its misassembly has profound consequences on protein networks essential for behavioral control. These results are also relevant for the interpretation of previous as well as for the design of future studies on DISC1.
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http://dx.doi.org/10.3389/fnmol.2018.00026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808171PMC
February 2018

Growth performance and protective effect of vitamin E on oxidative stress pufferfish (Takifugu obscurus) following by ammonia stress.

Fish Physiol Biochem 2018 Apr 18;44(2):735-745. Epub 2018 Jan 18.

Key Laboratory of Ecology and Environmental Science of Guangdong Higher Education Institutes, Guangdong Provincial Key Laboratory for Healthy and Safe Aquaculture, School of Life Science, South China Normal University, Guangzhou, 510631, People's Republic of China.

This study was conducted to determine the effects of vitamin E on growth performance, biochemical parameters, and antioxidant capacity of pufferfish (Takifugu obscurus) exposed to ammonia stress. The experimental basal diets supplemented with vitamin E at the rates of 2.31 (control), 21.84, 40.23, 83.64, 158.93, and 311.64 mg kg dry weight were fed to fish for 60 days. After the feeding trial, the fish were exposed to 100 mg L ammonia-nitrogen for 48 h. The results shown that the vitamin E group significantly improved weight gain, specific growth rate, and the expression levels of growth hormone receptors and insulin-like growth factor. Fish fed with the vitamin E-supplemented diets could increase plasma alkaline phosphatase activities and decrease plasma glutamicoxalacetic transaminase and glutamic-pyruvic transaminase activities. The relative expression levels of heat shock proteins (40.23-311.64 mg kg vitamin E diet group), manganese superoxide dismutase (83.64-158.93 mg kg vitamin E diet group), catalase (40.23-311.64 mg kg vitamin E diet group), and glutathione reductase (40.23-311.64 mg kg vitamin E diet group) were upregulated. On the other hand, the decreased level of reactive oxygen species (ROS) was observed in the 83.64-311.64 mg kg vitamin E additive group. These results showed that vitamin E might have a potentially useful role as an effective antioxidant to improve resistance in pufferfish.
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http://dx.doi.org/10.1007/s10695-018-0468-2DOI Listing
April 2018

Applying a "Big Data" Literature System to Recommend Antihypertensive Drugs for Hypertension Patients with Diabetes Mellitus.

Med Sci Monit 2018 Jan 7;24:114-148. Epub 2018 Jan 7.

Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China (mainland).

BACKGROUND The explosive increase in medical literature has changed therapeutic strategies, but it is challenging for physicians to keep up-to-date on the medical literature. Scientific literature data mining on a large-scale of can be used to refresh physician knowledge and better improve the quality of disease treatment. MATERIAL AND METHODS This paper reports on a reformulated version of a data mining method called MedRank, which is a network-based algorithm that ranks therapy for a target disease based on the MEDLINE literature database. MedRank algorithm input for this study was a clear definition of the disease model; the algorithm output was the accurate recommendation of antihypertensive drugs. Hypertension with diabetes mellitus was chosen as the input disease model. The ranking output of antihypertensive drugs are based on the Joint National Committee (JNC) guidelines, one through eight, and the publication dates, ≤1977, ≤1980, ≤1984, ≤1988, ≤1993, ≤1997, ≤2003, and ≤2013. The McNemar's test was used to evaluate the efficacy of MedRank based on specific JNC guidelines. RESULTS The ranking order of antihypertensive drugs changed with the date of the published literature, and the MedRank algorithm drug recommendations had excellent consistency with the JNC guidelines in 2013 (P=1.00 from McNemar's test, Kappa=0.78, P=1.00). Moreover, the Kappa index increased over time. Sensitivity was better than specificity for MedRank; in addition, sensitivity was maintained at a high level, and specificity increased from 1997 to 2013. CONCLUSIONS The use of MedRank in ranking medical literature on hypertension with diabetes mellitus in our study suggests possible application in clinical practice; it is a potential method for supporting antihypertensive drug-prescription decisions.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769362PMC
http://dx.doi.org/10.12659/msm.907015DOI Listing
January 2018

The protective effects of vitamin C on apoptosis, DNA damage and proteome of pufferfish (Takifugu obscurus) under low temperature stress.

J Therm Biol 2018 Jan 13;71:128-135. Epub 2017 Nov 13.

Key Laboratory of Ecology and Environmental Science of Guangdong Higher Education Institutes, Guangdong Provincial Key Laboratory for Healthy and Safe Aquaculture, School of Life Science, South China Normal University, Guangzhou 510631, PR China. Electronic address:

The aim of this study was to investigate the protective effects of vitamin C on apoptosis, DNA damage and proteome of pufferfish under low temperature stress. Six diets were formulated to contain 2.60, 48.90, 95.50, 189.83, 382.40, 779.53mg/kg vitamin C. After 8-week feeding trial, fish were exposed to low temperature challenge. The results showed that pufferfish receiving vitamin C diet exhibited a significant decrease in ROS production (48.9-189.83mg/kg vitamin C diet groups), cytoplasmic free-Ca concentration (48.9-779.53mg/kg vitamin C diet groups), apoptotic cell ratio (95.5-779.53mg/kg vitamin C diet groups) and DNA damage (189.83-779.53mg/kg vitamin C diet groups) under low temperature stress in comparison with those of control. We also investigated the alteration in protein expression under low temperature stress by a comparative proteomic analysis. The results demonstrated that 24 protein spots showed significantly differential expression in the cold-stress-treated group compared with those of the control group, and 5 protein spots were successfully identified. Furthermore, comparative proteomic analysis revealed that vitamin C could increase expressed proteins related to energy metabolism, immune responses and cytoskeleton. These findings would be helpful to understand the protective effects of vitamin C against cold stress.
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http://dx.doi.org/10.1016/j.jtherbio.2017.11.004DOI Listing
January 2018

Oxidative burst activity in haemocytes of the freshwater prawn Macrobrachium rosenbergii.

Fish Shellfish Immunol 2018 Feb 22;73:272-278. Epub 2017 Dec 22.

Key Laboratory of Ecology and Environment Science in Guangdong Higher Education, Guangdong Provincial Key Laboratory for Healthy and Safe Aquaculture, School of Life Sciences, South China Normal University, Guangzhou 510631, People's Republic of China. Electronic address:

Oxidative burst, release of reactive oxygen species/reactive nitrogen species (ROS/RNS) contributed to microorganisms killing, is a vital immune response of crustacean haemocyte. Three morphologic haemocyte types (hyaline cells, HC; semigranular cells, SGC; granular cells, GC) have been defined in crustaceans, and found to play different roles in immune defense. However, oxidative burst activities of different haemocyte subpopulations in crustaceans are currently not documented. In the present study, we investigated the oxidative burst activities of the three haemocyte types in the freshwater prawn Macrobrachium rosenbergii using the common ROS fluorescent probe dichlorofluorescin-diacetate (DCFH-DA). Nitric oxide (NO) donor sodium nitroprusside (SNP) improved the DCF fluorescence in haemocytes, while NO scavenger C-PTIO (2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) and NO-synthase inhibitor N-monomethyl-l-arginine (L-NMMA) reduced the fluorescence, suggesting that DCF fluorescence intensity could also be modified by intracellular NO level and activity of NO-synthase pathway. ROS/RNS was also produced in the untreated haemocytes. GC contained most non-induced ROS/RNS production, while oxidative activity of HC was rather weak. No significant impact of PMA could be observed on ROS/RNS level in all the three cell types. Both zymosan A (ZA) and lipopolysaccharide (LPS) significantly triggered the production of ROS/RNS in SGC and GC, whereas they had no effect on those of HC, suggesting that SGC and GC were the primary cell types involved in pathogens killing by ROS/RNS pathway. Cytochalasin B (Cyt B) inhibited the ZA-induced ROS/RNS production, but could not change the ROS/RNS level stimulated by LPS. For unstimulated haemocytes, ROS/RNS productions decreased 29.6%, 44.1% and 48.6% in SGC, and decreased 44.5%, 28.4% and 57.3% in GC, in the presence of L-NMMA, Fccp and DPI respectively, whereas apocynin could not modulate DCF fluorescence in both SGC and GC, suggesting that mitochondrial oxidative pathway was relatively more dominant in SGC, and NO-synthase (NOS) pathway appeared more active in GC. For LPS-stimulated haemocytes, oxidative activities decreased 22.9%, 42.9%, 29.6% and 60.0% in SGC, and reduced 40.6%, 25.2%, 26.7% and 70.6% in GC with the presence of L-NMMA, apocynin, Fccp and DPI respectively, suggesting that NADPH-oxidase (NOX) pathway in both SGC and GC was activated by LPS, and it became the predominant oxidative pathway in stimulated SGC, while NOS pathway was the relative main source for ROS/RNS production in stimulated GC.
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http://dx.doi.org/10.1016/j.fsi.2017.12.028DOI Listing
February 2018

Effects of high temperature on biochemical parameters, oxidative stress, DNA damage and apoptosis of pufferfish (Takifugu obscurus).

Ecotoxicol Environ Saf 2018 Apr 4;150:190-198. Epub 2018 Jan 4.

Key Laboratory of Ecology and Environmental Science of Guangdong Higher Education Institutes, Guangdong Provincial Key Laboratory for Healthy and Safe Aquaculture, School of Life Science, South China Normal University, Guangzhou 510631, PR China. Electronic address:

Water temperature is an important environmental factor that affects physiology and biochemical activities of fish. In this study, we investigated of high temperature on biochemical parameters, oxidative stress, DNA damage and apoptosis of pufferfish. Thermal stress could significantly increase the levels of AST, ALT, LDH, GLU and TG, whereas the levels of ALP and TP decrease significantly. In addition, thermal stress also decreased total blood cell count, inhibited cell viability, and subsequently lead to DNA damage and apoptosis. The mRNA levels of p53, caspase-9 and caspase-3 were up-regulated under thermal stress. These results suggested that caspase-dependent and p53 signaling pathways could play important roles in thermal stress-induced apoptosis in fish. Furthermore, the gene expression of SOD, CAT, HSP90 and C3 were induced by thermal stress. This study provides new insights into the mechanism whereby thermal stress affects physiological responses and apoptosis in pufferfish.
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http://dx.doi.org/10.1016/j.ecoenv.2017.12.045DOI Listing
April 2018

Sustained opioid antagonism modulates striatal sensitivity to baby schema in opioid use disorder.

J Subst Abuse Treat 2018 02 18;85:70-77. Epub 2017 Oct 18.

Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Behavioral Health Service, Veterans Administration Medical Center, Philadelphia, PA, USA.

Background: Chronic opioid misuse is associated with reduced sensitivity to natural rewards and social motivation deficits that include impaired caregiving. The neurobiological mechanisms underlying these deficits and their response to treatment are not well understood. Baby schema (Kindchenschema) is a set of juvenile physical features, which is perceived as "cute" and triggers motivation for caregiving. Recent studies suggest that the "baby schema effect" is mediated by the brain "reward" network. We studied the impact of opioid antagonist treatment on the baby schema response in patients with opioid use disorder.

Methods: Forty-seven (24 F) recently detoxified patients with opioid use disorder underwent functional magnetic resonance imaging (fMRI) while viewing infant portraits that were parametrically manipulated for baby schema content and rating them for cuteness, at baseline and during treatment with the injectable extended release opioid antagonist naltrexone (XRNTX). The study was not placebo-controlled.

Results: The behavioral effect of baby schema, indexed by "cuteness" ratings, was present and unaffected by XRNTX. The brain response to baby schema was absent at baseline, but present in the bilateral ventral striatum after two weeks of XRNTX treatment. The decline in self-reported craving for opioids was positively correlated with the brain fMRI response to baby schema in the bilateral ventral striatum.

Conclusions: Opioid antagonist treatment modulated the brain reward system response to a marker of caregiving motivation in patients with opioid use disorder. Neural response to baby schema may offer a novel probe of social motivation and affiliative behaviors in this population.
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http://dx.doi.org/10.1016/j.jsat.2017.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043353PMC
February 2018

Intra-nasal dopamine alleviates cognitive deficits in tgDISC1 rats which overexpress the human DISC1 gene.

Neurobiol Learn Mem 2017 Dec 28;146:12-20. Epub 2017 Oct 28.

Center for Behavioral Neuroscience, Institute of Experimental Psychology, Heinrich Heine University Düsseldorf, Germany. Electronic address:

The Disrupted-in-Schizophrenia 1 (DISC1) gene has been associated with mental illnesses such as major depression and schizophrenia. The transgenic DISC1 (tgDISC1) rat, which overexpresses the human DISC1 gene, is known to exhibit deficient dopamine (DA) homeostasis. To ascertain whether the DISC1 gene also impacts cognitive functions, 14-15 months old male tgDISC1 rats and wild-type controls were subjected to the novel object preference (NOP) test and the object-based attention test (OBAT) in order to assess short-term memory (1 h), long-term memory (24 h), and attention.

Results: The tgDISC1 group exhibited intact short-term memory, but deficient long-term-memory in the NOP test and deficient attention-related behavior in the OBAT. In a different group of tgDISC1 rats, 3 mg/kg intranasally applied dopamine (IN-DA) or its vehicle was applied prior to the NOP or the OBAT test. IN-DA reversed cognitive deficits in both the NOP and OBAT tests. In a further cohort of tgDISC1 rats, post-mortem levels of DA, noradrenaline, serotonin and acetylcholine were determined in a variety of brain regions. The tgDISC1 group had less DA in the neostriatum, hippocampus and amygdala, less acetylcholine in neostriatum, nucleus accumbens, hippocampus, and amygdala, more serotonin in the nucleus accumbens, and less serotonin and noradrenaline in the amygdala.

Conclusions: Our findings show that DISC1 overexpression and misassembly is associated with deficits in long-term memory and attention-related behavior. Since behavioral impairments in tgDISC1 rats were reversed by IN-DA, DA deficiency may be a major cause for the behavioral deficits expressed in this model.
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http://dx.doi.org/10.1016/j.nlm.2017.10.015DOI Listing
December 2017

Effect of dietary astaxanthin on the growth performance, non-specific immunity, and antioxidant capacity of pufferfish (Takifugu obscurus) under high temperature stress.

Fish Physiol Biochem 2018 Feb 21;44(1):209-218. Epub 2017 Sep 21.

South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center (SCS-REPIC), Guangzhou, People's Republic of China.

The present study was conducted to investigate the effects of astaxanthin on growth performance, biochemical parameters, ROS production, and immune-related gene expressions of the pufferfish (Takifugu obscurus) under high temperature stress. The experimental basal diets supplemented with astaxanthin at the rates of 0 (control), 20, 40, 80, 160, and 320 mg kg were fed to fish for 8 weeks. The results showed that the fish fed diet with 80, 160, and 320 mg kg astaxanthin significantly improved weight gain and specific growth rate. Furthermore, fish fed the moderate dietary astaxanthin increased plasma alkaline phosphatase activities, and decrease plasma aspartate aminotransferase and alanine aminotransferase activities. After the feeding trial, the fish were exposed to high temperature stress for 48 h. The results shown that astaxanthin could suppress ROS production induced by high temperature stress. Meanwhile, compared with the control group, the astaxanthin groups increased SOD, CAT, and HSP70 mRNA levels under high temperature stress. These results showed that the basal diet supplemented with 80-320 mg kg astaxanthin could enhance growth, nonspecific immune responses, and antioxidant defense system and improve resistance against high temperature stress in pufferfish.
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http://dx.doi.org/10.1007/s10695-017-0425-5DOI Listing
February 2018

Individual differences in the processing of smoking-cessation video messages: An imaging genetics study.

Biol Psychol 2017 09 28;128:125-131. Epub 2017 Jul 28.

Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Annenberg Public Policy Center, University of Pennsylvania, Philadelphia, PA 19104, United States; Corporal Michael J. Crescenz Veterans Administration Medical Center, Philadelphia, PA 19104, United States. Electronic address:

Studies testing the benefits of enriching smoking-cessation video ads with attention-grabbing sensory features have yielded variable results. Dopamine transporter gene (DAT1) has been implicated in attention deficits. We hypothesized that DAT1 polymorphism is partially responsible for this variability. Using functional magnetic resonance imaging, we examined brain responses to videos high or low in attention-grabbing features, indexed by "message sensation value" (MSV), in 53 smokers genotyped for DAT1. Compared to other smokers, 10/10 homozygotes showed greater neural response to High- vs. Low-MSV smoking-cessation videos in two a priori regions of interest: the right temporoparietal junction and the right ventrolateral prefrontal cortex. These regions are known to underlie stimulus-driven attentional processing. Exploratory analysis showed that the right temporoparietal response positively predicted follow-up smoking behavior indexed by urine cotinine. Our findings suggest that responses to attention-grabbing features in smoking-cessation messages is affected by the DAT1 genotype.
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http://dx.doi.org/10.1016/j.biopsycho.2017.07.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731475PMC
September 2017
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