ABSTRACT
BACKGROUND: Limited evidence exists about suicide risk in persons with polycystic ovary syndrome (PCOS). OBJECTIVE: To assess suicide risk in persons with PCOS, accounting for psychiatric comorbid conditions and age group. DESIGN: Cohort study. SETTING: Data from the Taiwanese nationwide database from 1997 to 2012. PATIENTS: A cohort of 18 960 patients diagnosed with PCOS, each matched with control participants in a 1:10 ratio on the basis of age, psychiatric comorbid conditions, urbanization level, and income. Suicide attempts were evaluated using Cox regression models. MEASUREMENTS: Suicide risk with hazard ratios (HRs). RESULTS: Participants with PCOS had a notable 8.47-fold increase in risk for suicide attempt compared with the control group (HR, 8.47 [95% CI, 7.54 to 9.51]), after adjustment for demographic characteristics, psychiatric comorbid conditions, Charlson Comorbidity Index scores, and frequency of all-cause clinical visits. The elevated risk was evident across the adolescent (HR, 5.38 [CI, 3.93 to 7.37]), young adult (<40 years; HR, 9.15 [CI, 8.03 to 10.42]), and older adult (HR, 3.75 [CI, 2.23 to 6.28]) groups. Sensitivity analyses involving the exclusion of data from the first year or the first 3 years of observation yielded consistent results. LIMITATION: Potential underestimation of PCOS and mental disorder prevalence due to use of administrative claims data; lack of clinical data, such as body mass index and depressive symptoms; and no assessment of a confounding effect of valproic acid exposure. CONCLUSION: This study underscores the heightened risk for suicide attempt that persons with PCOS face, even after adjustment for demographics, psychiatric comorbid conditions, physical conditions, and all-cause clinical visits. This suggests the importance of routine monitoring of mental health and suicide risk in persons diagnosed with PCOS. PRIMARY FUNDING SOURCE: Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and Ministry of Science and Technology of Taiwan.
Subject(s)
Mental Disorders , Polycystic Ovary Syndrome , Female , Adolescent , Young Adult , Humans , Aged , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/diagnosis , Polycystic Ovary Syndrome/epidemiology , Cohort Studies , Suicide, Attempted , Retrospective Studies , Mental Disorders/complications , Mental Disorders/epidemiologyABSTRACT
AIM: Large language models (LLMs) have been suggested to play a role in medical education and medical practice. However, the potential of their application in the psychiatric domain has not been well-studied. METHOD: In the first step, we compared the performance of ChatGPT GPT-4, Bard, and Llama-2 in the 2022 Taiwan Psychiatric Licensing Examination conducted in traditional Mandarin. In the second step, we compared the scores of these three LLMs with those of 24 experienced psychiatrists in 10 advanced clinical scenario questions designed for psychiatric differential diagnosis. RESULT: Only GPT-4 passed the 2022 Taiwan Psychiatric Licensing Examination (scoring 69 and ≥ 60 being considered a passing grade), while Bard scored 36 and Llama-2 scored 25. GPT-4 outperformed Bard and Llama-2, especially in the areas of 'Pathophysiology & Epidemiology' (χ2 = 22.4, P < 0.001) and 'Psychopharmacology & Other therapies' (χ2 = 15.8, P < 0.001). In the differential diagnosis, the mean score of the 24 experienced psychiatrists (mean 6.1, standard deviation 1.9) was higher than that of GPT-4 (5), Bard (3), and Llama-2 (1). CONCLUSION: Compared to Bard and Llama-2, GPT-4 demonstrated superior abilities in identifying psychiatric symptoms and making clinical judgments. Besides, GPT-4's ability for differential diagnosis closely approached that of the experienced psychiatrists. GPT-4 revealed a promising potential as a valuable tool in psychiatric practice among the three LLMs.
Subject(s)
Psychiatry , Taiwan , Humans , Diagnosis, Differential , Educational Measurement/standards , Mental Disorders/diagnosis , Adult , PsychiatristsABSTRACT
Pinus taiwanensis Hayata (Pinaceae) is an endemic plant in Taiwan. According to the Chinese Materia Medica Grand Dictionary, the Pinus species is mainly used to relieve pain, and eliminate pus and toxicity. In this study, nineteen compounds were isolated from the ethyl acetate layer of the ethanolic extract of P. taiwanensis Hayata twigs using bioassay-guided fractionation, and their anti-melanoma effects were investigated through a B16-F10 mouse melanoma cell model. The structures of the purified compounds were identified by 2D-NMR, MS, and IR, including 1 triterpenoid, 9 diterpenoids, 2 lignans, 4 phenolics, 1 phenylpropanoid, 1 flavonoid, and 1 steroid. Among them, compound 3 was found to be a new diterpene. Some of the compounds (2, 5, 6, 17, 18) showed moderate cytotoxicity effects. On the other hand, the anti-melanoma effect was no better than that from the original ethyl acetate layer. We presumed it resulted from the synergistic effect, although further experimentation needs to be performed.
Subject(s)
Lignans , Melanoma, Experimental , Pinus , Animals , Lignans/chemistry , Melanoma, Experimental/drug therapy , Mice , Pinus/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , TaiwanABSTRACT
BACKGROUND: We previously showed the efficacy of bi-anodal transcranial direct current stimulation (tDCS) over the prefrontal cortex (PFC) regions with extracephalic reference placement in improving negative symptoms in schizophrenia. In this ancillary investigation, the effects of this intervention on insight levels, other clinical outcomes, and cardio-respiratory and autonomic functions were examined and the potential of biomarkers for treatment response was explored. METHODS: Schizophrenia patients were randomly allocated to receive 10 sessions of bi-anodal tDCS over the PFC regions with extracephalic reference placement (2 mA, 20 minutes, twice daily for 5 weeks) or sham stimulation. We examined, in 60 patients at baseline, immediately after stimulation and at follow-up visits, the insight levels, other clinical outcomes, blood pressure, respiratory rate, heart rate, and heart rate variability. RESULTS: Insight levels as assessed by the abbreviated version of the Scale to Assess Unawareness in Mental Disorder in schizophrenia awareness of the disease, positive and negative symptoms dimensions, and beliefs about medication compliance as assessed by Medication Adherence Rating Scale were significantly enhanced by active stimulation relative to sham. No effects were observed on cognitive insight, other clinical outcomes, or cardio-respiratory and autonomic functions. Heart rate variability indices as biomarkers were not associated with the clinical response to the intervention. CONCLUSIONS: Our results provide evidence for bi-anodal tDCS over the PFC regions with extracephalic reference placement in heightening the levels of insight into the disease and symptoms, as well as beliefs about medication compliance in schizophrenia, without impacting other clinical outcomes and cardio-respiratory/autonomic functions.
Subject(s)
Autonomic Nervous System/physiopathology , Diagnostic Self Evaluation , Prefrontal Cortex/physiopathology , Schizophrenia/physiopathology , Schizophrenia/therapy , Transcranial Direct Current Stimulation , Vital Signs/physiology , Adult , Biomarkers , Blood Pressure/physiology , Double-Blind Method , Female , Heart Rate/physiology , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Respiratory Rate/physiology , Transcranial Direct Current Stimulation/methodsABSTRACT
BACKGROUND: Previous studies have shown elevated cancer risk in anorexia nervosa but the literature on other eating disorders (EDs) is scarce. This study aimed to investigate the association between all EDs and esophageal, stomach, and other cancers. METHODS: We used a retrospective cohort design, based on a two-million randomized longitudinal health insurance dataset, a sub-dataset of Taiwan's National Health Insurance Research Database. From all the potential participants aged 20 years or more, a total of 6,628 participants were enrolled, including 1,657 patients with EDs, with sex-, age-, and indexed date-matched (1:3) 4,971 controls. Each participant was individually tracked from 2000 to 2015 to identify incident cases of cancers, including esophageal cancer (EC), stomach cancer (SC), and all other cancers (AOC). The multivariate Cox proportional hazards model was employed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between EDs and cancer. RESULTS: Of the total 6,628 enrollees, 222 in 1,657 individuals with EDs and 810 in the 4,971 non-ED control individuals developed cancer (1,262.40 vs. 1,472.15 per 100,000 person-years), and the Kaplan-Meier survival analysis was not statistically significant (log-rank, p = .324). However, after adjusting for covariates, the risk of EC and SC among the individuals with an ED was significantly higher, with adjusted HRs of 5.32 (95% CI: 1.07-26.49, p < .001) and 4.61 (95% CI: 1.91-11.14, p < .001), respectively. EDs were not associated with other cancers. CONCLUSIONS: This study provides evidence for the association between EDs and the risk for EC and SC. Further research on mechanisms and prevention is therefore needed.
Subject(s)
Esophageal Neoplasms , Feeding and Eating Disorders , Stomach Neoplasms , Cohort Studies , Esophageal Neoplasms/epidemiology , Feeding and Eating Disorders/epidemiology , Humans , Incidence , Proportional Hazards Models , Retrospective Studies , Risk Factors , Stomach Neoplasms/epidemiology , Taiwan/epidemiologyABSTRACT
OBJECTIVE: To investigate the risk of psychiatric disorders after traumatic brain injury (TBI), and to clarify whether the post-TBI rehabilitation was associated with a lower risk of developing psychiatric disorders. DESIGN: A register-based, retrospective cohort design. SETTING: Using data from the National Health Insurance Research Database of Taiwan, we established an exposed cohort with TBI and a nonexposed group without TBI matched by age and year of diagnosis between 2000 and 2015. PARTICIPANTS: This study included 231,894 patients with TBI and 695,682 patients without TBI (N=927,576). INTERVENTIONS: Rehabilitation therapies in TBI patients. MAIN OUTCOME MEASURES: A multivariable Cox proportional hazards regression model was used to compare the risk of developing psychiatric disorders. RESULTS: The incidence rate of psychiatric disorders was higher in the TBI group than the control group. Compared with the control group, the risk of psychiatric disorders in the TBI group was twofold (hazard ratio [HR]=2.072; 95% confidence interval [95% CI], 1.955-2.189; P<.001). Among the participants with TBI, 49,270 (21.25%) had received rehabilitation therapy and had a lower risk of psychiatric disorders (HR=0.691; 95% CI, 0.679-0.703; P<.001). In the subgroup analysis, the medium- to high-level intensity rehabilitation therapy was associated with lower risks of psychiatric disorder (HR=0.712 and 0.568, respectively), but there was no significant finding in the low-intensity group. CONCLUSIONS: We found that TBI was associated with a high risk for developing psychiatric disorders, and that the post-TBI rehabilitation significantly reduced the risk of psychiatric disorders in a dose-dependent manner.
Subject(s)
Brain Injuries, Traumatic/epidemiology , Mental Disorders/epidemiology , Adolescent , Adult , Brain Injuries, Traumatic/rehabilitation , Case-Control Studies , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Occupational Therapy/statistics & numerical data , Physical Therapy Modalities/statistics & numerical data , Proportional Hazards Models , Registries , Retrospective Studies , Taiwan/epidemiology , Young AdultABSTRACT
BACKGROUND: The risk of injury directly related to hospitalization for motor vehicle accidents (MVAs) in the obstructive sleep apnea (OSA) patients has not been thoroughly understood. Our study aimed to examine the association between the OSA and the hospitalization for an MVA injury. METHODS: This retrospective cohort study used Taiwan's National Health Insurance Research Database (NHIRD) between 2000 and 2015. The OSA patients aged ≥20 years by age, sex, and index-year matched by non-OSA controls were enrolled (1:3). We used the Cox proportional regression model to evaluate the association between the OSA and the hospitalization for an MVA injury. RESULTS: The incidence rate of hospitalization for an MVA injury was higher in the OSA cohort (N = 3025) when compared with the non-OSA controls (N = 9075), as 575.3 and 372.0 per 100,000 person-years, respectively (p < 0.001). The Kaplan-Meier analysis showed that the OSA cohort had a significantly higher incidence of hospitalization for the MVA injury (log-rank test, p < 0.001). After adjusting for the covariates, the risk of hospitalization for the MVA injury among the OSA was significantly higher (hazard ratio [HR] =2.18; 95% confidence interval [CI] = 1.79-2.64; p < 0.001). Stimulants usage was associated with a nearly 20% decrease in the risk of an overall hospitalization for an MVA injury in the OSA patients. CONCLUSIONS: This study provides evidence that patients with OSA are at a two-fold higher risk of developing hospitalization for an MVA injury, and the usage of modafinil and methylphenidate was associated with a lower risk of an overall hospitalization for the MVA injury.
Subject(s)
Accidents, Traffic/prevention & control , Accidents, Traffic/statistics & numerical data , Central Nervous System Stimulants/therapeutic use , Hospitalization/trends , Sleep Apnea, Obstructive/drug therapy , Adult , Aged , Databases, Factual , Female , Humans , Kaplan-Meier Estimate , Male , Methylphenidate/therapeutic use , Middle Aged , Modafinil/therapeutic use , Motor Vehicles , Proportional Hazards Models , Retrospective Studies , Risk Factors , Sleep Apnea, Obstructive/epidemiology , Taiwan/epidemiology , Young AdultABSTRACT
AIM: This study aimed to investigate the association between males with pinworm infections and the risk of developing psychiatric disorders. METHOD: A total of 2044 enrolled patients, with 511 pinworm subjects and 1533 unexposed subjects (1:3) matched for sex, age and index year, from Taiwan's Longitudinal Health Insurance Database (LHID) from 2000 to 2015, selected from the National Health Insurance Research Database (NHIRD). After adjusting for confounding factors, the Cox regression model was used to compare the risk of developing psychiatric disorders during the 15â¯years of follow-up. RESULTS: Of all the enrollees, 24 in the pinworm cohort and 18 in the unexposed cohort (343.10 vs 84.96 per 100,000 person-year) developed psychiatric disorders. The Cox regression model revealed that, after adjusting for sex, age, monthly income, urbanization level, geographic region, and comorbidities, the adjusted HR was 4.581 (95% CI: 2.214-9.480, pâ¯<â¯.001, pâ¯<â¯.001). Pinworm infections were associated with the increased risk in anxiety disorders, depressive disorders, and sleep disorders, respectively. CONCLUSION: Patients who suffered from pinworm infections have a higher risk of developing psychiatric disorders, and this finding should be considered as a timely reminder for the clinicians to provide much more attention for these patients because of their mental health issues.
Subject(s)
Enterobiasis/epidemiology , Enterobiasis/psychology , Mental Disorders/epidemiology , Mental Disorders/psychology , Adolescent , Adult , Aged , Child , Child, Preschool , Cohort Studies , Comorbidity , Databases, Factual , Enterobiasis/diagnosis , Female , Follow-Up Studies , Humans , Infant , Longitudinal Studies , Male , Mental Disorders/diagnosis , Middle Aged , Retrospective Studies , Risk Factors , Taiwan/epidemiology , Young AdultABSTRACT
Pentachloropseudilin (PClP) is a chlorinated phenylpyrrole compound that was first isolated from Actinoplanes (ATCC33002), and its structure has been confirmed by chemical synthesis. PClP shows broad antimicrobial activity against Gram-negative and Gram-positive bacteria, protozoa, fungi, and yeast. In mammalian cells, PClP is known to act as a reversible and allosteric inhibitor of myosinâ 1c (Myo1c). Herein, we report that PCIP is a potent inhibitor of transforming growth factor-ß (TGF-ß)-stimulated signaling. PCIP inhibits TGF-ß-stimulated Smad2/3 phosphorylation and plasminogen activator inhibitor-1 (PAI-1) promoter activation with an IC50 of 0.1â µm in target cells (A549, HepG2, and Mv1Lu cells). In addition, PCIP attenuates TGF-ß-stimulated expression of vimentin, N-cadherin, and fibronectin and, thus, blocks TGF-ß-induced epithelial to mesenchymal transition (EMT) in these cells. Furthermore, cell-surface labeling and immunoblot analysis indicates that PCIP suppresses TGF-ß-stimulated cellular responses by attenuating cell-surface expression of the typeâ II TGF-ß receptor through accelerating caveolae-mediated internalization followed by primarily lysosome-dependent degradation of the receptor, as demonstrated by sucrose density gradient analysis and immune fluorescence staining.
Subject(s)
Hydrocarbons, Chlorinated/pharmacology , Pyrroles/pharmacology , Receptor, Transforming Growth Factor-beta Type II/agonists , Transforming Growth Factor beta/drug effects , Animals , Cell Line , Epithelial-Mesenchymal Transition/drug effects , Extracellular Matrix/drug effects , Extracellular Matrix/metabolism , Humans , Myosin Type I/genetics , Myosin Type I/metabolism , Smad Proteins/metabolism , Transforming Growth Factor beta/metabolismABSTRACT
Impaired quality of life (QoL) is a common and clinically relevant feature of schizophrenia. In the present study, we attempted to formulate a model of QoL in the chronic stage of schizophrenia by including key variables-namely cognitive insight, self-stigma, insight into treatment, and medication compliance-that were proposed as its significant predictors in previous studies. We employed structural equation modeling (SEM) to simultaneously test the associations between these variables. A total of 170 community-dwelling patients with schizophrenia participated in this study. Cognitive insight, self-stigma, insight into treatment, medication compliance, and QoL were assessed through self-reporting. Symptoms were rated by interviewers. The influences of cognitive insight, stigma, insight into treatment, and medication compliance on QoL were supported using SEM. Our findings indicated that cognitive insight had a significant, positive, and direct effect on both self-stigma and insight into treatment; in contrast, it had a negative and direct effect on medication compliance. Notably, no evidence indicated a direct effect of cognitive insight on QoL. Thus, individuals with high cognitive insight reported low QoL because of stigma, low medication compliance, and their increased insight into treatment. In contrast, cognitive insight might indirectly ameliorate QoL mediated by the effect of insight into treatment on medication compliance. The findings provide additional support of the links between cognitive and clinical insight, self-stigma, medication compliance, and QoL in those with schizophrenia and suggest the need for screening and intervention services appropriate for this high-risk population.
Subject(s)
Cognition Disorders/etiology , Patient Compliance , Quality of Life/psychology , Schizophrenia/complications , Schizophrenic Psychology , Social Stigma , Adult , Aged , Cognition Disorders/psychology , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Self Concept , Self Report , Statistics, Nonparametric , Surveys and Questionnaires , Young AdultABSTRACT
Pentabromopseudilin (PBrP) is a marine antibiotic isolated from the marine bacteria Pseudomonas bromoutilis and Alteromonas luteoviolaceus. PBrP exhibits antimicrobial, anti-tumour, and phytotoxic activities. In mammalian cells, PBrP is known to act as a reversible and allosteric inhibitor of myosin Va (MyoVa). In this study, we report that PBrP is a potent inhibitor of transforming growth factor-ß (TGF-ß) activity. PBrP inhibits TGF-ß-stimulated Smad2/3 phosphorylation, plasminogen activator inhibitor-1 (PAI-1) protein production and blocks TGF-ß-induced epithelial-mesenchymal transition in epithelial cells. PBrP inhibits TGF-ß signalling by reducing the cell-surface expression of type II TGF-ß receptor (TßRII) and promotes receptor degradation. Gene silencing approaches suggest that MyoVa plays a crucial role in PBrP-induced TßRII turnover and the subsequent reduction of TGF-ß signalling. Because, TGF-ß signalling is crucial in the regulation of diverse pathophysiological processes such as tissue fibrosis and cancer development, PBrP should be further explored for its therapeutic role in treating fibrotic diseases and cancer.
Subject(s)
Lysosomes/drug effects , Lysosomes/metabolism , Myosin Type V/antagonists & inhibitors , Protein Serine-Threonine Kinases/antagonists & inhibitors , Pyrroles/pharmacology , Receptors, Transforming Growth Factor beta/antagonists & inhibitors , Transforming Growth Factor beta/antagonists & inhibitors , Alteromonas/chemistry , Animals , Cell Line , Dose-Response Relationship, Drug , HEK293 Cells , Hep G2 Cells , Humans , Mink , Molecular Structure , Myosin Type V/metabolism , Protein Serine-Threonine Kinases/biosynthesis , Pseudomonas/chemistry , Pyrroles/chemistry , Pyrroles/isolation & purification , Receptor, Transforming Growth Factor-beta Type II , Receptors, Transforming Growth Factor beta/biosynthesis , Structure-Activity Relationship , Transforming Growth Factor beta/metabolismABSTRACT
PURPOSE: The transforming growth factor-beta (TGF-ß) pathway is an important in the initiation and progression of cancer. Due to a strong association between an elevated colorectal cancer risk and increase fecal excretion of cholest-4-en-3-one, we aim to determine the effects of cholest-4-en-3-one on TGF-ß signaling in the mink lung epithelial cells (Mv1Lu) and colorectal cancer cells (HT29) in vitro. METHODS: The inhibitory effects of cholest-4-en-3-one on TGF-ß-induced Smad signaling, cell growth inhibition, and the subcellular localization of TGF-ß receptors were investigated in epithelial cells using a Western blot analysis, luciferase reporter assays, DNA synthesis assay, confocal microscopy, and subcellular fractionation. RESULTS: Cholest-4-en-3-one attenuated TGF-ß signaling in Mv1Lu cells and HT29 cells, as judged by a TGF-ß-specific reporter gene assay of plasminogen activator inhibitor-1 (PAI-1), Smad2/3 phosphorylation and nuclear translocation. We also discovered that cholest-4-en-3-one suppresses TGF-ß responsiveness by increasing lipid raft and/or caveolae accumulation of TGF-ß receptors and facilitating rapid degradation of TGF-ß and thus suppressing TGF-ß-induced signaling. CONCLUSIONS: Our results suggest that cholest-4-en-3-one inhibits TGF-ß signaling may be due, in part to the translocation of TGF-ß receptor from non-lipid raft to lipid raft microdomain in plasma membranes. Our findings also implicate that cholest-4-en-3-one may be further explored for its potential role in colorectal cancer correlate to TGF-ß deficiency.
Subject(s)
Colorectal Neoplasms/genetics , Plasminogen Activator Inhibitor 1/genetics , Protein Serine-Threonine Kinases/genetics , Receptors, Transforming Growth Factor beta/genetics , Transforming Growth Factor beta1/genetics , Animals , Cholestenones/administration & dosage , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Epithelial Cells/pathology , HT29 Cells , Humans , Lung/pathology , Membrane Microdomains/drug effects , Membrane Microdomains/genetics , Membrane Microdomains/metabolism , Mink/genetics , Phosphorylation , Plasminogen Activator Inhibitor 1/biosynthesis , Protein Serine-Threonine Kinases/biosynthesis , Proteolysis/drug effects , Receptor, Transforming Growth Factor-beta Type I , Receptors, Transforming Growth Factor beta/biosynthesis , Signal Transduction/drug effects , Transforming Growth Factor beta1/biosynthesisABSTRACT
OBJECTIVE: Stigma resistance (SR) has recently emerged as a prominent aspect of research on recovery from schizophrenia, partly because studies have suggested that the development of stigma-resisting beliefs may help individuals lead a fulfilling life and recover from their mental illness. The present study assessed the relationship between personal SR ability and prediction variables such as self-stigma, self-esteem, self-reflection, coping styles, and psychotic symptomatology. METHOD: We performed an exploratory cross-sectional study of 170 community-dwelling patients with schizophrenia. Self-stigma, self-esteem, self-reflection, coping skills, and SR were assessed through self-report. Psychotic symptom severity was rated by the interviewers. Factors showing significant association in univariate analyses were included in a stepwise backward regression model. RESULTS: Stepwise regressions revealed that acceptance of stereotypes of mental illness, self-esteem, self-reflection, and only 2 adaptive coping strategies (positive reinterpretation and religious coping) were significant predictors of SR. The prediction model accounted for 27.1% of the variance in the SR subscale score in our sample. CONCLUSIONS: Greater reflective capacity, greater self-esteem, greater preferences for positive reinterpretation and religious coping, and fewer endorsements of the stereotypes of mental illness may be key factors that relate to higher levels of SR. These factors are potentially modifiable in tailored interventions, and such modification may produce considerable improvements in the SR of the investigated population. This study has implications for psychosocial rehabilitation and emerging views of recovery from mental illness.
Subject(s)
Adaptation, Psychological/physiology , Resilience, Psychological , Schizophrenia/physiopathology , Schizophrenic Psychology , Self Concept , Social Stigma , Adult , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
For clinical application, there is a great need for small-molecule inhibitors (SMIs) that could control pathogenic effects of transforming growth factor (TGF-ß) and/or modulate effects of TGF-ß in normal responses. Selective SMIs of the TGF-ß signaling pathway developed for therapeutics will also be powerful tools in experimentally dissecting this complex pathway, especially its cross-talk with other signaling pathways. In this study, we characterized (1'R,5'S,6'S)-2-(3',5'-dibromo-1',6'-dihydroxy-4'-oxocyclohex-2'-enyl) acetonitrile (DT), a member of a new class of small-molecule inhibitors related to bromotyrosine derivate from Pseudoceratina sp., which inhibits the TGF-ß type I receptor serine/threonine kinase known as activin receptor-like kinase (ALK) 5. The inhibitory effects of DT on TGF-ß-induced Smad signaling and epithelial-to-mesenchymal transition (EMT) were investigated in epithelial cells using in vitro kinase assay, luciferase reporter assays, immunoblotting, confocal microscopy, and wound healing assays. The novel ALK5 inhibitor, DT, inhibited the TGF-ß-stimulated transcriptional activations of 3TP-Lux. In addition, DT decreased phosphorylated Smad2/3 levels and the nuclear translocation of Smad2/3 increased by TGF-ß. In addition, DT inhibited TGF-ß-induced EMT and wound healing of A549 cells. Our results suggest that DT is a potential therapeutic agent for fibrotic disease and cancer treatment. J. Cell. Biochem. 117: 2800-2814, 2016. © 2016 Wiley Periodicals, Inc.
Subject(s)
Acetonitriles/pharmacology , Cyclohexanones/pharmacology , Enzyme Inhibitors/pharmacology , Lung Neoplasms/drug therapy , Porifera/chemistry , Protein Serine-Threonine Kinases/antagonists & inhibitors , Receptors, Transforming Growth Factor beta/antagonists & inhibitors , Transforming Growth Factor beta/pharmacology , Tyrosine/analogs & derivatives , Animals , Apoptosis/drug effects , Blotting, Western , Cell Proliferation/drug effects , Epithelial-Mesenchymal Transition/drug effects , Fluorescent Antibody Technique , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Phosphorylation/drug effects , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Receptor, Transforming Growth Factor-beta Type I , Receptors, Transforming Growth Factor beta/genetics , Receptors, Transforming Growth Factor beta/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effects , Smad Proteins/genetics , Smad Proteins/metabolism , Tumor Cells, Cultured , Tyrosine/pharmacologyABSTRACT
BACKGROUND: Chronic periodontitis and gingivitis are associated with various diseases; however, their impact on dementia is yet to be elucidated. This study is aimed at investigating the association between chronic periodontitis and gingivitis, and the risk of developing dementia. METHODS: A total of 2,207 patients, with newly diagnosed chronic periodontitis and gingivitis between January 1, 2000 and December 31, 2000, were selected from the National Health Insurance Research Database of Taiwan, along with 6,621 controls matched for sex and age. After adjusting for confounding factors, Cox proportional hazards analysis was used to compare the risk of developing dementia during the 10-year follow-up period. RESULTS: Of the study subjects, 25 (1.13%) developed dementia compared to 61 (0.92%) in the control group. Cox proportional hazards regression analysis revealed that the study subjects were more likely to develop dementia (hazard ratio (HR) 2.085, 95% CI 1.552-4.156, p < 0.001). After adjusting for sex, age, monthly income, urbanization level, geographic region, and comorbidities, the HR for dementia was 2.54 (95% CI 1.297-3.352, p = 0.002). CONCLUSIONS: Patients with chronic periodontitis and gingivitis have a higher risk of developing dementia. However, further studies on other large or national data sets are required to support the current findings.
Subject(s)
Chronic Periodontitis/epidemiology , Dementia/epidemiology , Gingivitis/epidemiology , Adult , Aged , Cohort Studies , Comorbidity , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Taiwan , Young AdultABSTRACT
BACKGROUND: Reduced health-related quality of life in the physical domain (HRQOLphysical) has been reported to increase risks for cardiovascular disease (CVD); however, the mechanism underlying this phenomenon is still unclear. The autonomic nervous system (ANS) that connects the body and mind is a biologically plausible candidate to investigate this mechanism. The aim of our study is to examine whether the HRQOLphysical independently contributes to heart rate variability (HRV), which reflects ANS activity. METHODS: We recruited 329 physically and mentally healthy adults. All participants completed Beck Anxiety Inventory, Beck Depression Inventory and World Health Organization Questionnaire on Quality of Life: Short Form-Taiwanese version (WHOQOL-BREF). They were divided into groups of individuals having high or low scores of HRQOLphysical as discriminated by the quartile value of WHOQOL-BREF. We obtained the time and frequency-domain indices of HRV, namely variance (total HRV), the low-frequency power (LF; 0.05-0.15 Hz), which may reflect baroreflex function, the high-frequency power (HF; 0.15-0.40 Hz), which reflects cardiac parasympathetic activity, and the LF/HF ratio. RESULTS: There was an independent contribution of HRQOLphysical to explaining the variance in HRV after excluding potential confounding factors (gender, age, physical activity, alcohol use, depression and anxiety). Compared with the participants with high levels of HRQOLphysical, those with low levels of HRQOLphysical displayed significant reductions in variance and LF. CONCLUSIONS: This study highlights the independent role of low HRQOLphysical in contributing to the reduced HRV in healthy adults and points to a potential underlying mechanism for HRQOLphysical to confer increased risks for CVD.
Subject(s)
Anxiety Disorders/psychology , Arrhythmias, Cardiac/psychology , Quality of Life , Adult , Anxiety Disorders/complications , Arrhythmias, Cardiac/complications , Exercise , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Surveys and Questionnaires , Taiwan , Young AdultABSTRACT
Inflammation has been considered important in the pathogenesis of schizophrenia. Increasing evidence reveals that patients with schizophrenia have abnormal expression of cytokines, which are related to development of metabolic abnormalities. Metabolic abnormality has become a critical issue, though its longitudinal relationship with the disorder, such as the antipsychotics influence, is unclear. We aimed to investigate whether abnormalities of metabolic parameters and cytokine levels in acute exacerbated schizophrenic patients existed, and whether intervention of antipsychotic could help. The present study analyzed peripheral cytokines and metabolic/hemodynamic parameters in healthy controls and acute exacerbated schizophrenic patients hospitalized for three weeks under the unique treatment of quetiapine, a well-known second-generation antipsychotic. Our results showed that patients with schizophrenia were predisposed to metabolic abnormalities in acute exacerbation, including body mass index (BMI) and waist circumference (WC). The patients were also prone to dysglycemia, lower high-density lipoprotein cholesterol (HDL-c) levels, and higher blood pressure with concomitant of elevation of interleukin (IL)-2, IL-6 and IL-10 in which IL-6 was associated with BMI. After quetiapine treatment, IL-2, IL-6 and IL-10 remained higher than the controls, but IL-10 was significantly decreased in follow-up comparison. Glycemic-related indexes, HDL-c and IL-10 levels were significantly changed by variance analysis. Results of the present study imply that acute exacerbated schizophrenic patients with metabolism abnormalities may involve disruption of expression of cytokines, and that quetiapine may have therapeutic effects. Nonetheless, metabolism parameters of patients undergoing treatment with quetiapine should be closely monitored.