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1.
Anal Chem ; 95(34): 12974-12981, 2023 08 29.
Article in English | MEDLINE | ID: mdl-37590447

ABSTRACT

Fat mass and obesity-associated proteins (FTO) play an essential role in the reversible regulation of N6-methyladenosine (m6A) epigenetic modification, and the overexpression of FTO is closely associated with the occurrence of diverse human diseases (e.g., obesity and cancers). Herein, we demonstrate the construction of multiple DNAzymes driven by single base elongation and ligation for the single-molecule monitoring of FTO in cancer tissues. When target FTO is present, the m6A-RNA is specifically demethylated and subsequently acts as a primer to combine with the padlock probe, initiating single-base elongation and ligation reaction to generate a closed template probe. Upon the addition of phi29 DNA polymerase, a rolling circle amplification (RCA) reaction is initiated to produce large numbers of Mg2+-dependent DNAzyme repeats. Subsequently, the DNAzymes cyclically digest the signal probes, liberating numerous Cy5 molecules that can be precisely counted by single-molecule imaging. Taking advantage of the sequence specificity of the polymerase/ligase-mediated gap-filling and ligation as well as the high amplification efficiency of RCA, this biosensor shows excellent specificity and high sensitivity with a detection limit of 5.96 × 10-16 M. It can be applied to screen FTO inhibitors and quantify FTO activity at the single-cell level. Moreover, the proposed strategy can accurately distinguish the FTO expression level in tissues of healthy individuals and breast cancer patients, providing a new platform for drug discovery, m6A modification-related research, and clinical diagnostics.


Subject(s)
Breast Neoplasms , DNA, Catalytic , Humans , Female , Drug Discovery , Epigenesis, Genetic , Obesity , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics
2.
Medicine (Baltimore) ; 102(28): e34304, 2023 Jul 14.
Article in English | MEDLINE | ID: mdl-37443496

ABSTRACT

To investigate the value of parameters of the pulmonary artery and right ventricular function in predicting the 30-day poor prognosis of patients with acute pulmonary embolism (APE). The heart rate, respiratory rate, systolic blood pressure, Wells score for APE, history of recent operation or immobilization, history of cancer, respiratory failure, smoking were significantly (P < .05) different among the control, good prognosis, and poor prognosis groups. The maximal short diameter of the right and left ventricle (RVD/LVD) ratio (P < .001) and left pulmonary artery (LPA) (P = .01) were significantly different between the good and poor prognosis groups. Systolic blood pressure (odds ratio [OR]: 0.98, P = .045) and the RVD/LVD ratio (OR: 12.57, P = .02) were significant independent risk factors for poor prognosis. The risk for poor prognosis significantly increased when the RVD/LVD ratio was >1.11 (cutoff value) with the area under the curve (AUC) of 0.71 (95% confidence interval [CI]: 0.61-0.80, P < .001). LPA (OR: 9.12, P = .01) and RVD/LVD (OR: 4.62, P = .012) were the significant independent risk factors for poor prognosis in the central pulmonary embolism. The LPA of 2.1 cm had the highest predictive value for poor prognosis in the central APE (AUC: 0.68; sensitivity 84.6%; specificity 53.1%). The RVD/LVD ratio and systolic blood pressure are significant risk factors for short-term prognosis in patients with APE. When the LPA is >2.1 cm in the central APE or the RVD/LVD is >1.11, the risk of poor prognosis increases, which can be used as important indicators for predicting the prognosis of patients with APE. Two hundred forty-three APE patients and 61 patients without APE who underwent computed tomographic pulmonary angiography (CTPA) were retrospectively enrolled as the experimental and the control group, respectively. APE patients who were followed up at the 30-day time point were divided into the good prognosis (n = 195) and poor prognosis group (n = 32). The main pulmonary artery (MPA) to the aorta (AO) ratio, maximal diameter of the LPA and right pulmonary artery (RPA), ratio of the RVD/LVD and the height and volume of the pulmonary artery (PAh and PAV, respectively) were analyzed after indexing to the body surface area.


Subject(s)
Hominidae , Pulmonary Embolism , Ventricular Dysfunction, Right , Humans , Animals , Ventricular Dysfunction, Right/diagnostic imaging , Ventricular Dysfunction, Right/etiology , Retrospective Studies , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/complications , Prognosis , Angiography
4.
Eur Urol ; 82(5): 543-550, 2022 11.
Article in English | MEDLINE | ID: mdl-36050131

ABSTRACT

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common paediatric soft-tissue sarcoma. Approximately 15-20% of RMS cases arise from the bladder and prostate (B/P). The optimal treatment strategy for B/P RMS remains unclear. OBJECTIVE: To retrospectively evaluate the applicability of our procedure performed to treat paediatric patients with B/P RMS. DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective analysis from a single tertiary referral hospital. From August 2003 to March 2021, 62 children pathologically diagnosed with B/P RMS underwent radical cystectomy and orthotopic detaenial sigmoid neobladder reconstruction in our centre. SURGICAL PROCEDURE: Surgical procedures included laparoscopic radical cystectomy and detaenial sigmoid neobladder reconstruction, which is demonstrated in the accompanying video. MEASUREMENTS: Demographic, clinical, and follow-up data were collected. Perioperative and long-term oncological and functional outcomes were reported. A logistic regression analysis was also performed. RESULTS AND LIMITATIONS: All surgeries, including three intracorporeal laparoscopic surgeries, were completed successfully. Of the 62 patients, 54 were alive without evidence of disease recurrence or metastasis at the last follow-up. Five of the 14 >12-yr-old boys reported that they experienced erections. Two female patients >12 yr old reported that they menstruated. However, this was a retrospective study conducted at a single centre with limited surgeon experience. CONCLUSIONS: Our results confirmed the safety and feasibility of primary orthotopic sigmoid neobladder reconstruction after radical cystectomy for paediatric patients with B/P RMS. Good outcomes in terms of oncological control and functional recovery were achieved. The high histocompatibility and tissue adaptability of children are inspiring. PATIENT SUMMARY: We describe our stepwise technique of radical cystectomy and detaenial sigmoid neobladder reconstruction for paediatric patients with bladder and prostate rhabdomyosarcoma. With this technique, we were able to achieve good functional recovery without compromising cancer control and significantly increasing complications.


Subject(s)
Prostatic Neoplasms , Rhabdomyosarcoma , Urinary Bladder Neoplasms , Urinary Diversion , Child , Cystectomy/adverse effects , Cystectomy/methods , Follow-Up Studies , Humans , Male , Neoplasm Recurrence, Local/surgery , Prostate , Prostatic Neoplasms/surgery , Retrospective Studies , Rhabdomyosarcoma/etiology , Rhabdomyosarcoma/surgery , Treatment Outcome , Urinary Bladder , Urinary Bladder Neoplasms/diagnosis , Urinary Diversion/adverse effects , Urinary Diversion/methods
5.
Medicine (Baltimore) ; 101(31): e30026, 2022 Aug 05.
Article in English | MEDLINE | ID: mdl-35945710

ABSTRACT

To investigate the normal diameter of the abdominal aorta and common iliac arteries of the middle-aged and elderly people in China and the relationship of the diameters with age, sex, height, weight, body mass index (BMI), and body surface area (BSA). This retrospective study enrolled 625 patients including 380 males and 245 females aged 60.00 years (interquartile range 13.00 years). All clinical data and the diameters of the abdominal aorta and common iliac arteries were analyzed. The diameter of the abdominal aorta was 21.49 ± 2.49 mm at the proximal, 16.94 (interquartile range 2.39) mm at the middle, and 15.65 (interquartile range 2.90) mm at the distal segment. The diameter of the common iliac artery was 10.76 (interquartile range 1.99) mm at the right proximal, 10.41 (interquartile range 2.05) mm at the left proximal, 10.74 (interquartile range 2.25) mm at the right distal, and 10.67 (interquartile range 2.22) mm at the left distal segment. The height, weight, BSA, BMI, diameters of the proximal, middle and distal abdominal aorta as well as the proximal and distal left and right common iliac arteries were significantly higher in males than those in females (P < .001). Height, weight, BSA, and BMI were significantly (P < .001) positively correlated with the diameter of the abdominal aorta and common iliac artery at the proximal, middle, and distal segments. The middle and distal diameters of the abdominal aorta were significantly higher in males than those in females (P < .05). The diameter of the abdominal aorta at the proximal, middle, and distal segment as well as the diameter of the left and right common iliac artery at the distal segment were significantly (P < .05) increased with age. The normal values of the diameter of the abdominal aorta and common iliac arteries are suggested for the middle-aged and elderly Chinese people for clinical reference. The diameters are gender related and significantly positively correlated with BSA, height, weight, and BMI, which is beneficial for the diagnosis and treatment planning of relevant vascular diseases.


Subject(s)
Aorta, Abdominal , Iliac Artery , Aged , Aorta, Abdominal/diagnostic imaging , Body Surface Area , China , Female , Humans , Iliac Artery/diagnostic imaging , Male , Middle Aged , Retrospective Studies
6.
Chem Commun (Camb) ; 58(73): 10229-10232, 2022 Sep 13.
Article in English | MEDLINE | ID: mdl-36004508

ABSTRACT

We demonstrate for the first time the utilization of fluorogenic RNA aptamers for label-free uracil-DNA glycosylase (UDG) assay. Through rationally engineering the transcription machine with dU substitution, this assay requires only a single probe to simultaneously sense and amplify the UDG signal, achieving a low detection limit of 6.3 × 10-6 U mL-1. Moreover, it can be applied for screening UDG inhibitors and measuring endogenous UDG activity in different cells.


Subject(s)
Aptamers, Nucleotide , DNA Repair , Uracil-DNA Glycosidase/metabolism
7.
J Int Med Res ; 50(1): 3000605211067688, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34986677

ABSTRACT

OBJECTIVE: To begin to understand how to prevent deep vein thrombosis (DVT) after an innovative operation termed intracorporeal laparoscopic reconstruction of detenial sigmoid neobladder, we explored the factors that influence DVT following surgery, with the aim of constructing a model for predicting DVT occurrence. METHODS: This retrospective study included 151 bladder cancer patients who underwent intracorporeal laparoscopic reconstruction of detenial sigmoid neobladder. Data describing general clinical characteristics and other common parameters were collected and analyzed. Thereafter, we generated model evaluation curves and finally cross-validated their extrapolations. RESULTS: Age and body mass index were risk factors for DVT, whereas postoperative use of hemostatic agents and postoperative passive muscle massage were significant protective factors. Model evaluation curves showed that the model had high accuracy and little bias. Cross-validation affirmed the accuracy of our model. CONCLUSION: The prediction model constructed herein was highly accurate and had little bias; thus, it can be used to predict the likelihood of developing DVT after surgery.


Subject(s)
Laparoscopy , Urinary Bladder Neoplasms , Venous Thrombosis , Humans , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Retrospective Studies , Risk Factors , Urinary Bladder Neoplasms/surgery , Venous Thrombosis/etiology , Venous Thrombosis/prevention & control
8.
Front Bioeng Biotechnol ; 10: 1078342, 2022.
Article in English | MEDLINE | ID: mdl-36588949

ABSTRACT

Introduction: Erythropoietin producing hepatocyte receptor A2 (EphA2) is widely presented in the tumor cells, closely related to tumor cell migration, not cell apoptosis and proliferation. Based on its high expression in castration-resistant prostate cancer (CRPC), we herein develop a CRISPR-Cas9-based genome-editing nanomedicine to target erythropoietin producing hepatocyte receptor A2 for the treatment of castration-resistant prostate cancer. Methods: To this end, TAT was designed to stabilize the distribution of calcium, and then bound to ribonucleoprotein (RNP) to form nanoparticles RNP@CaP-TAT. Results: This nanoparticle has a simple synthesis process with good biocompatible, to achieve the knockout of tumor cells (PC-3) targeting erythropoietin producing hepatocyte receptor A2 gene and to effectively suppress the migration of tumor cells. Discussion: This delivery genome editing system provides a promising gene therapy strategy for the treatment of castration-resistant prostate cancer, showing good potential against castration-resistant prostate cancer tumor metastasis. In addition, it can be extended to other types of cancer with highly heterogeneous gene expression.

9.
J Fish Biol ; 100(1): 192-202, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34716580

ABSTRACT

Interleukin-8 (IL-8) is a critical chemokine regulating immune cells' chemotaxis as well as their physiological or pathological activations. In fish cells, recombinant IL-8 proteins induced transcriptions of pro-inflammatory cytokines. Nonetheless, the exact mechanisms underlying the function of fish IL-8 as a pro-inflammatory cytokine are still unclear. In this paper, the authors first prepared recombinant grass carp IL-8 (rgcIL-8) using an Escherichia coli expression system, and later confirmed rgcIL-8 increased gene expression of il8, il1ß and tumour necrosis factor alpha (tnfα) in grass carp head kidney leukocytes (HKLs). Using signalling pathway inhibitors, the authors showed that rgcIL-8 regulated transcriptions of pro-inflammatory cytokines via MAPK and/or NF-κB signalling pathways. They cloned gcIL-8-specific receptor CXCR1 and subsequently discovered that gcIL-8 could increase the activity of NF-κB and the transcription of IL-1ß via CXCR1. Simultaneously, antibody neutralization assay showed that endogenous IL-8 is partially relevant to the self-regulation of IL-1ß. Moreover, rgcIL-8 led to the expression of inducible nitric oxide synthase gene, causing an accumulation of nitric oxide in the culture medium of HKLs, suggesting the potential of gcIL-8 to mediate inflammatory response. This study not only enriched the function of IL-8 in teleost but also revealed it as a potential target for the inflammatory control in grass carp.


Subject(s)
Carps , Fish Diseases , Animals , Carps/genetics , Fish Proteins , Head Kidney , Interleukin-8/genetics , Leukocytes , Signal Transduction
10.
Front Psychol ; 12: 670120, 2021.
Article in English | MEDLINE | ID: mdl-34658993

ABSTRACT

Citizenship pressure has recently been a hot topic in organizational citizenship behavior research since it aids in understanding the driving mechanism of organizational citizenship behavior. However, previous research has revealed discrepancies in the connection. This article develops a theoretical model of the impact of citizenship pressure on organizational citizenship performance based on expectancy theory. A leader-employee paired questionnaire was used to evaluate the hypotheses. The results indicate that organizational citizenship performance is positively influenced by citizenship pressure. The connection between organizational citizenship performance and citizenship pressure is positively moderated by transformational leadership. The better the transformational leadership, the greater the influence of citizenship pressure on organizational citizenship performance. Furthermore, the impact of transformational leadership on the link between citizenship pressure and organizational citizenship performance is dependent on the political skill of employees. When individuals with strong political skill encounter transformational leadership, the relationship between citizenship pressure and organizational citizenship performance is minimal. On the contrary, this relationship is enhanced when personnel with limited political skill are confronted with transformational leadership.

12.
J Clin Neurosci ; 89: 430-436, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34074598

ABSTRACT

OBJECTIVE: The purpose of this study was to perform a systematic review and meta-analysis on the association between insomnia and the risk of developing into metabolic syndrome (including hypertension, hyperglycemia, hyperlipidemia and obesity). METHOD: We conducted our research according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta Analyses). After the search term was determined, we searched Pubmed and Embase databases until December 1, 2020 for the observational studies. We used random effects models to aggregate risk estimates for individual studies and the odds ratio (OR) as well as 95% confidence intervals (CI) were calculated for pooled data. Heterogeneity in this study was assessed by using I2 statistic. RESULTS: 12 studies were eventually included in this meta-analysis which contained metabolic syndrome related symptoms (hypertension, hyperglycemia, hyperlipidemia and obesity). The combined OR value and 95% CI of the hypertension group was 1.41 (1.19-1.67). The hyperglycemia group was 1.29 (1.11-1.50). The hyperlipidemia group was 1.12 (0.92-1.37) and the obesity group was 1.31 (1.03-1.67). CONCLUSION: The risk of insomnia patients suffering from hypertension, hyperglycemia, hyperlipidemia and obesity in metabolic syndrome was 1.41 times, 1.29 times and 1.31 times than people without insomnia respectively.


Subject(s)
Metabolic Syndrome/epidemiology , Sleep Initiation and Maintenance Disorders/epidemiology , Humans , Hyperglycemia/epidemiology , Hypertension/epidemiology
13.
Clin Neuropharmacol ; 44(1): 5-8, 2021.
Article in English | MEDLINE | ID: mdl-33449474

ABSTRACT

INTRODUCTION: The efficacy of vitamin D for migraine remains controversial. We conduct a systematic review and meta-analysis to explore the influence of vitamin D versus placebo on treatment in migraine patients. METHODS: We search PubMed, EMbase, Web of Science, EBSCO, and Cochrane library databases through April 2020 for randomized controlled trials assessing the effect of vitamin D versus placebo on treatment efficacy in migraine patients. This meta-analysis is performed using the random-effect model. RESULTS: Five randomized controlled trials are included in the meta-analysis. Overall, compared with control group in migraine patients, vitamin D treatment is associated with substantially reduced number of headache days (standard mean difference [SMD], -0.53; 95% confidence interval [CI], -0.83 to -0.23; P = 0.0006), frequency of headache attacks (SMD, -1.09; 95% CI, -1.86 to -0.32; P = 0.006), headache severity (SMD, -0.55; 95% CI, -0.91 to -0.19; P = 0.0003), and Migraine Disability Assessment score (SMD, -0.76; 95% CI, -1.11 to -0.40; P < 0.0001). CONCLUSIONS: Vitamin D treatment is effective to alleviate migraine.


Subject(s)
Dietary Supplements , Migraine Disorders/drug therapy , Randomized Controlled Trials as Topic/methods , Vitamin D/administration & dosage , Humans , Migraine Disorders/diagnosis , Treatment Outcome
14.
Front Psychol ; 11: 1478, 2020.
Article in English | MEDLINE | ID: mdl-32848973

ABSTRACT

Most of the previous literature has focused on the positive effects of ethical leadership on organizations and employees, but some studies have unexpectedly found that ethical leadership is negatively related to employees' well-being at work. Based on the theory of workplace anxiety, this research explored whether ethical leadership can reduce employees' well-being at work by causing them to feel anxious about organizational citizenship behavior and whether organizational concern motivation moderates this mechanism. We collected 227 three-stage time-crossed data samples from 12 institutions in Hainan China, then tested our research hypotheses to confirm that ethical leadership has a negative impact on employees' well-being at work under certain conditions. We found that: (1) ethical leadership is significantly and positively correlated with the organizational citizenship anxiety perceived by employees, (2) organizational citizenship anxiety perceived by employees plays a completely mediating role between ethical leadership and employee well-being at work, and (3) organizational concern motivation not only negatively moderates the negative correlation between employees' organizational citizenship anxiety and well-being at work, but also further moderates the indirect negative effect of ethical leadership on employee well-being at work through organizational citizenship anxiety.

15.
J Transl Med ; 17(1): 101, 2019 03 28.
Article in English | MEDLINE | ID: mdl-30922329

ABSTRACT

BACKGROUND: SETD2, the single mediator of trimethylation of histone 3 at position lysine 36, has been reported associated with initiation progression and chemotherapy resistance in acute myeloid leukemia (AML). Whether polymorphisms of SETD2 affect prognosis and chemotherapy response of AML remains elusive. METHODS: Three tag single-nucleotide polymorphisms (tagSNPs) of SETD2 were genotyped in 579 AML patients by using Sequenom Massarray system. Association of the SNPs with complete remission (CR) rate after Ara-C based induction therapy, overall survival (OS) and relapse-free survival (RFS) were analyzed. RESULT: Survival analysis indicated that SETD2 rs76208147 TT genotype was significantly associated with poor prognosis of AML (TT vs. CC + CT hazard ratio: HR = 1.838, 95% confidence interval (CI) 1.005-3.360, p = 0.048). After adjusting for the known prognostic factors including risk stratification, age, allo-SCT, WBC count and LDH count, rs76208147 TT genotype was still associated with OS in the multivariate analysis (TT vs. CC + CT HR = 1.923, 95% CI 1.007-3.675, p = 0.048). In addition, after adjusting by other clinical features, patients with rs4082155 allele G carries showed higher rate of complete remission which indicated by CR rate (AG + GG vs. AA odd ratio (OR) = 0.544, 95% CI 0.338-0.876, p = 0.012). CONCLUSIONS: SETD2 genetic polymorphism is associated with AML prognosis and chemotherapy outcome, suggesting the possibility for development in AML diagnostics and therapeutics towards SETD2.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Histone-Lysine N-Methyltransferase/genetics , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Polymorphism, Single Nucleotide , Adolescent , Adult , Aged , China/epidemiology , Cytarabine/administration & dosage , Female , Follow-Up Studies , Genotype , Humans , Induction Chemotherapy , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Prognosis , Remission Induction , Survival Analysis , Treatment Outcome , Young Adult
16.
BMJ Open ; 6(11): e010707, 2016 11 30.
Article in English | MEDLINE | ID: mdl-27903557

ABSTRACT

OBJECTIVE: To evaluate the effectiveness of internet-based cognitive-behavioural therapy for insomnia (ICBT-i) in adults. DESIGN: A meta-analysis of ICBT-i. DATA SOURCES: Systematic searches of randomised controlled trials of ICBT-i were performed in the PubMed, EMBASE, PsycINFO and Cochrane Library databases up to 19 June 2016. REVIEW METHOD: 2 reviewers independently performed study selection, quality assessment and data extraction. Outcomes of interest included sleep onset latency (SOL), total sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO), number of nocturnal awakenings (NWAK), and Insomnia Severity Index (ISI). RevMan 5.2 and Stata 13.0 meta-analysis software were used to perform statistical analysis. RESULTS: 14 records for 15 studies (1013 experimental group participants, 591 waiting list group participants) were included. The meta-analysis indicated that, at the post-test time point, SOL decreased by 18.41 min (95% CI 13.60 to 23.21), TST increased by 22.30 min (95% CI 16.38 to 28.23), SE increased by 9.58% (95% CI 7.30% to 11.85%), WASO decreased by 22.31 min (95% CI 13.50 to 31.11), NWAK decreased by 0.52 (95% CI 0.28 to 0.76), and ISI decreased by 5.88 points (95% CI 4.29 to 7.46). Additionally SOL, TST, SE, and WASO exhibited statistically significant improvements at follow-up versus before treatment. CONCLUSIONS: ICBT-i is an effective treatment for adults with insomnia. This conclusion should be verified in further studies.


Subject(s)
Cognitive Behavioral Therapy , Sleep Initiation and Maintenance Disorders/therapy , Telemedicine , Therapy, Computer-Assisted , Adult , Female , Humans , Male , Randomized Controlled Trials as Topic , Sleep Initiation and Maintenance Disorders/psychology , Treatment Outcome
17.
PLoS One ; 10(11): e0142258, 2015.
Article in English | MEDLINE | ID: mdl-26581107

ABSTRACT

As the internet has become popularized in recent years, cognitive behavioral therapy for insomnia (CBT-i) has shifted from a face-to-face approach to delivery via the internet (internet-based CBT-i, ICBT-i). Several studies have investigated the effects of ICBT-i on comorbid anxiety and depression; however, the results remain inconclusive. Thus, a meta-analysis was conducted to determine the effects of ICBT-i on anxiety and depression. Electronic databases, including PubMed, EMBASE, PsycINFO and the Cochrane Library (throughout May 28, 2015), were systematically searched for randomized controlled trials (RCTs) of ICBT-i. Data were extracted from the qualified studies and pooled together. The standardized mean difference (SMD) and 95% confidence interval (95% CI) were calculated to assess the effects of ICBT-i on comorbid anxiety and depression. Nine records that included ten studies were ultimately qualified. The effect sizes (ESs) were -0.35 [-0.46, -0.25] for anxiety and -0.36 [-0.47, -0.26] for depression, which were stable using a between-group or within-group comparison and suggest positive effects of ICBT-i on both comorbid disorders. Although positive results were identified in this meta-analysis, additional high-quality studies with larger sample sizes are needed in the future.


Subject(s)
Cognitive Behavioral Therapy , Depressive Disorder/therapy , Sleep Initiation and Maintenance Disorders/therapy , Telemedicine , Anxiety Disorders/therapy , Depressive Disorder/physiopathology , Humans , Internet , Randomized Controlled Trials as Topic , Sleep Initiation and Maintenance Disorders/physiopathology
18.
Vet Immunol Immunopathol ; 160(3-4): 201-8, 2014 Aug 15.
Article in English | MEDLINE | ID: mdl-25001908

ABSTRACT

The Runt-related transcription factor (Runx) family consists of three members, Runx1, Runx2 and Runx3 in mammals, which are involved in various biological processes. Recent studies have demonstrated that Runx1 plays critical roles in the immunity of higher vertebrates. In fish, zebrafish and fugu Runx family members have been identified, and their chromosome location, promoter usage and expression patterns have been elucidated. However, their expression profiles in immune responses are still unknown. In this study, we identified grass carp five Runx1 (gcRunx1) variants (v1-5) possibly generated through alternative promoter usage and alternative splicing. The gcRunx1 v1-3 encodes the proteins possessing intact structural characteristics of Runx family, but the putative proteins of gcRunx1 v4-5 lack a transactivation domain, an inhibitory domain and a C-terminal pentapeptide motif (VWRPY). Tissue distribution assays revealed that gcRunx1 was preferentially expressed in some immune-related tissues including thymus and spleen, indicating its potential roles in teleost immunity. The changes of gcRunx1 expression to various immune stimuli was examined in periphery blood lymphocytes, showing that gcRunx1 v1-3 mRNA levels were increased after LPS, poly I:C and PHA treatment, whereas gcRunx1 v4-5 mRNA expression were stimulated only by LPS and PHA. Furthermore, in vivo studies confirmed that bacterial challenge enhanced gcRunx1 mRNA levels. In particular, in vitro and in vivo studies revealed that gcRunx1 v4-5 mRNA expression was induced with a delayed kinetics compared with that of gcRunx1 v1-3. These findings not only provide the evidence for the involvement of gcRunx1 in immune response, but also reveal the inducible expression diversity of fish Runx1 splicing variants, thereby facilitating further elucidating the role of Runx1 in piscine immunity.


Subject(s)
Carps/genetics , Carps/immunology , Core Binding Factor Alpha 2 Subunit/genetics , Core Binding Factor Alpha 2 Subunit/immunology , Fish Proteins/genetics , Fish Proteins/immunology , Genetic Variation , Alternative Splicing , Amino Acid Sequence , Animals , Bacterial Infections/genetics , Bacterial Infections/immunology , Bacterial Infections/veterinary , Carps/metabolism , Cloning, Molecular , Core Binding Factor Alpha 2 Subunit/chemistry , Fish Diseases/genetics , Fish Diseases/immunology , Fish Diseases/metabolism , Fish Proteins/chemistry , Molecular Sequence Data , Phylogeny , Promoter Regions, Genetic , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sequence Homology, Amino Acid , Tissue Distribution
19.
Endocrinology ; 155(7): 2355-62, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24735326

ABSTRACT

Prader-Willi syndrome (PWS) is a genetic disease characterized by persistent hunger and hyperphagia. The lack of the Snord116 small nucleolar RNA cluster has been identified as the major contributor to PWS symptoms. The Snord116 deletion (Snord116del) mouse model manifested a subset of PWS symptoms including hyperphagia and hyperghrelinemia. In this study, male Snord116del mice were characterized and tested for their acute and chronic responses to anorexic substances related to the ghrelin pathway. In comparison with their wild-type littermates, the food intake rate of Snord116del mice was 14% higher when fed ad libitum, and 32% to 49% higher within 12 hours after fasting. Fasted Snord116del mice were less sensitive to the acute anorexic effect of competitive antagonist [d-Lys(3)]-GHRP6, YIL-781, and reverse agonist [d-Arg(1),d-Phe(5),d-Trp(7,9),Leu(11)]-substance P (SPA) of ghrelin receptor GHS-R. All 3 GHS-R inhibitors failed to inhibit chronic food intake of either Snord116del or wild-type mice due to rapid adaptation. Although fasted Snord116del mice had normal sensitivity to the acute anorexic effect of glucagon-like peptide 1 receptor agonist exenatide, those fed ad libitum required a higher dose and more frequent delivery to achieve ∼15% suppression of long-term food intake in comparison with wild-type mice. Ghrelin, however, is unlikely to be essential for the anorexic effect of exenatide in fed mice, as shown by the fact that exenatide did not reduce ghrelin levels in fed mice and food intake of ghrelin(-/-) mice fed ad libitum could be suppressed by exenatide. In conclusion, this study suggests that GHS-R may not be an effective therapeutic target, and in contrast, exenatide may produce anorexic effect in PWS individuals.


Subject(s)
Anorexia/genetics , Peptides/pharmacology , Prader-Willi Syndrome/genetics , RNA, Small Nucleolar/genetics , Receptors, Ghrelin/antagonists & inhibitors , Venoms/pharmacology , Analysis of Variance , Animals , Anorexia/metabolism , Anorexia/physiopathology , Disease Models, Animal , Eating/drug effects , Eating/genetics , Eating/physiology , Exenatide , Fasting/blood , Ghrelin/blood , Ghrelin/genetics , Ghrelin/metabolism , Humans , Hyperphagia/genetics , Hyperphagia/metabolism , Hyperphagia/physiopathology , Hypoglycemic Agents/pharmacology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Oligopeptides/pharmacology , Piperidines/pharmacology , Prader-Willi Syndrome/metabolism , Prader-Willi Syndrome/physiopathology , Quinazolinones/pharmacology , RNA, Small Nucleolar/metabolism , Receptors, Ghrelin/metabolism , Substance P/analogs & derivatives , Substance P/pharmacology
20.
Asian Pac J Trop Med ; 6(7): 548-51, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23768827

ABSTRACT

OBJECTIVE: To determine whether alpha lipoic acid (LA) can effectively protect lenses from hydrogen peroxide (H2O2)-induced cataract. METHODS: Lens from adult Sprague-Dawley rats were cultured in 24-well plates and treated without or with 0.2 mM of H2O2, 0.2 mM of H2O2 plus 0.5 mM, 1.0 mM, or 2.0 mM of LA for 24 h. Cataract was assessed using cross line grey scale measurement. Superoxide dismutase (SOD), glutathione (GSH-Px), lactate dehydrogenase (LDH), and malondialdehyde (MDA) activity or level in lens homogenates was measured. Apoptosis of lens epithelial cells in each group were detected by Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) Assay. RESULTS: A total of 0.2 mM of H2O2 induced obvious cataract formation and apoptosis in lens' epithelial cells, but 0.5-2.0 mM of LA could block the effect of 0.2 mM H2O2 in inducing cataract and apoptosis. Furthermore, 0.2 mM of H2O2 significantly decreased SOD, GSH-Px, and LDH activity and significant increased MDA level in the lens, but 0.5-2.0 mM of LA blocked the effect of 0.2 mM H2O2. One mM of LA was found to be the most effective. CONCLUSIONS: LA can protect lens from H2O2-induced cataract. LA exerts protective effects through inhibition of lens' epithelial cell apoptosis and activation of anti-oxidative enzymes.


Subject(s)
Antioxidants/pharmacology , Apoptosis/drug effects , Cataract/prevention & control , Lens, Crystalline/pathology , Thioctic Acid/pharmacology , Animals , Cataract/pathology , Epithelial Cells , Glutathione/metabolism , Hydrogen Peroxide/toxicity , L-Lactate Dehydrogenase/metabolism , Malondialdehyde/metabolism , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/metabolism
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