Association between vitiligo and risk of retinal detachment: A population-based cohort study in Taiwan.

BACKGROUND: Vitiligo is reportedly associated with several ocular abnormalities. However, the relationship between vitiligo and retinal detachment (RD) remains unclear. OBJECTIVE: This study examined the risk of RD among vitiligo patients. PATIENTS AND METHODS: A nationwide population-based cohort study was conducted using data from the Taiwan National Health Insurance Database between 2007 and 2018. A total of 21,132 vitiligo patients were 1:4 matched with non-vitiligo patients by age, sex, and propensity score of comorbidities. Cumulative incidence and Cox proportional hazard models were used to investigate the risk of RD in vitiligo patients. Subgroup analysis was performed. RESULTS: The vitiligo cohort had a significantly higher RD rate than the non-vitiligo cohort (adjusted hazard ratio, 1.44; 95% confidence interval, 1.20-1.72; P-value <0.001). Vitiligo patients who required treatments such as phototherapy, systemic corticosteroids, or immunosuppressants exhibited an even greater risk (adjusted hazard ratio, 1.57; 95% confidence interval, 1.16-2.14; P-value 0.004). CONCLUSION: Our study revealed a 1.44-fold increased risk of RD in vitiligo patients with an even higher risk in patients receiving phototherapy, systemic corticosteroids or immunosuppressants. The risk remains consistently higher over a 10-year follow-up period.

A Network Comparison of Sexual Dysfunction, Psychological Factors, and Body Dissociation between Individuals with and without Sexual Trauma Histories.

Sexual dysfunction is associated with psychological symptoms, including depression and anxiety. Sexual dysfunctions are often attributed to dissociation symptoms in individuals who reported sexual trauma histories. This study utilized a network approach to analyze relationships between sexual and psychological symptoms and examine whether the identified network structures differed between individuals who reported a history of sexual trauma and those who did not. Sexual dysfunction, history of sexual trauma, internalizing symptoms, dissociation symptoms, sex-related shame, and negative body image were assessed in 1,937 United States college students (women = 69.5%). Nearly half (46.8%) of the participants reported a sexual trauma history in their lifetime. Using regularized partial correlation networks, the relationships between sexual and psychological symptoms were analyzed and compared between groups with and without trauma histories. Internalizing symptoms were positively correlated with sexual dysfunction regardless of the presence of sexual trauma history. Anxiety had a stronger influence in the trauma network than in the no-trauma network. Feeling separated from the body during sexual activity was a central symptom and was related to difficulties relaxing and enjoying sex only in the trauma network. Sex-related shame appeared to play a more important role in men compared to women. To improve clinical practice of assessing and treating sexual dysfunction, researchers and clinicians should consider core symptoms that connect different aspects of sexual and psychological functioning while being aware of the unique role of dissociation in the context of traumatic stress.

Psychometric Properties and Clinical Utility of CBCL and P-GBI Sleep Items in Children and Adolescents.

OBJECTIVE: Sleep is crucial to overall health, playing a complex role in a wide range of mental health concerns in children and adults. Nevertheless, clinicians may not routinely assess sleep problems due to lack of awareness or limitations such as cost or time. Scoring sleep-related items embedded on broader scales may help clinicians get more out of tools they are already using. The current study explores evidence of reliability, validity, and clinical utility of sleep-related items embedded on two caregiver-report tools: the Child Behavior Checklist (CBCL) and Parent General Behavior Inventory (P-GBI). METHOD: Youth aged 5-18 years and their parents were recruited from both an academic medical center (N = 759) and an urban community health center (N = 618). Caregivers completed the CBCL and P-GBI as part of a more comprehensive outpatient evaluation. Exploratory factor analyses, multi-group confirmatory factor analyses, and graded response models evaluated dimensionality, reliability, and invariance across samples. Correlations and receiver operating characteristic curve analyses probed associations with diagnostic and demographic variables. RESULTS: Two subscales emerged for each itemset. Across both samples, P-GBI sleep subscales were more reliable and consistent than CBCL sleep subscales, showed greater coverage of sleepiness and insomnia constructs, were better at discriminating individuals within a wider range of sleep complaints, and showed significant correlation with mood disorder diagnoses. CONCLUSIONS: The P-GBI sleep items provide a brief, reliable measure for assessing distinct dimensions of sleep complaints and detecting mood symptoms or diagnoses related to the youth's sleep functioning, making them a useful addition to clinical practice.

Association between chronic kidney disease and risk of bullous pemphigoid: a nationwide population-based cohort study.

BACKGROUND: Studies have shown that bullous pemphigoid (BP) occurs in patients with chronic kidney disease (CKD). However, the risk of developing BP in patients with CKD remains inconclusive. OBJECTIVE: To investigate whether CKD increases the risk of BP. METHODS: Participants were recruited from the National Health Insurance Database of Taiwan between 2007 and 2018. Overall, 637,664 newly diagnosed patients with CKD and 637,664 age-, sex-, and comorbidity-matched non-CKD participants were selected. A competing risk model was used to evaluate the risk of development of BP. RESULTS: After adjusting for age, sex, and comorbid diseases in the multivariate model, CKD was a significant risk factor for BP (adjusted hazard ratio [aHR]: 1.29; 95% confidence interval [CI]: 1.17-1.42; p < 0.001). CKD patients were classified into the dialytic or non-dialytic groups and compared to non-CKD participants, and this revealed that patients with dialysis-dependent CKD had the highest risk of BP (aHR 1.75; 95% CI 1.51-2.03), followed by patients with non-dialysis-dependent CKD (aHR 1.20; 95% CI 1.08-1.32). LIMITATIONS: We lacked detailed laboratory data on the severity of CKD. CONCLUSIONS: Compared with individuals without CKD, those with CKD had a 1.3-fold increased risk of BP. Patients with dialysis-dependent CKD had an even higher BP risk (1.8-fold).

Fluorescence detection of apolipoprotein E gene polymorphisms based on oligonucleotide ligation and magnetic separation.

Alzheimer's disease is a progressive neurodegenerative condition that causes brain cell death and is the leading cause of dementia. Most patients with Alzheimer's disease are diagnosed with late-onset Alzheimer's disease (LOAD), with apolipoprotein E (APOE) genotypes being highly associated with the frequency of LOAD risk. A fluorescence detection system coupled with oligonucleotide ligation and magnetic separation was developed to identify two single-nucleotide polymorphisms (SNPs) for the APOE gene and recognize APOE alleles for LOAD. The system utilized a fluorescence probe with one base-discriminating nucleoside for SNP (F probe) and a perfectly complementary biotin-modified sequence against the target DNA (P probe). When the F and P probes matched the target DNA sequences, DNA ligation occurred, and ligation products were produced. Streptavidin magnetic beads were subsequently employed to remove the ligation products, and a decrease in fluorescence intensity was observed in the supernatant compared to when there was no target DNA. This system detected two SNPs of APOE alleles, namely rs429358 and rs7412. The results indicated that the R-values ((F0 - F1)/F0) for rs429358 were 0.92 ± 0.002 for the T/T target, 0.47 ± 0.004 for the T/C target and 0.11 ± 0.004 for the C/C target, respectively. The R-values for rs7412 were 0.73 ± 0.009 for the C/C target, 0.42 ± 0.001 for the C/T target and 0.16 ± 0.007 for the T/T target, respectively. F0 and F1 represent the fluorescence intensity of the F probe without and with target DNA, respectively. Based on fluorescence intensity, the fluorescence detection system was able to identify the genotypes of the APOE gene accurately to evaluate the risk of Alzheimer's disease.

CVM-1118 (foslinanib), a 2-phenyl-4-quinolone derivative, promotes apoptosis and inhibits vasculogenic mimicry via targeting TRAP1.

CVM-1118 (foslinanib) is a phosphoric ester compound selected from 2-phenyl-4-quinolone derivatives. The NCI 60 cancer panel screening showed CVM-1125, the major active metabolite of CVM-1118, to exhibit growth inhibitory and cytotoxic effects at nanomolar range. CVM-1118 possesses multiple bioactivities, including inducing cellular apoptosis, cell cycle arrest at G2/M, as well as inhibiting vasculogenic mimicry (VM) formation. The TNF receptor associated protein 1 (TRAP1) was identified as the binding target of CVM-1125 using nematic protein organization technique (NPOT) interactome analysis. Further studies demonstrated CVM-1125 reduced the protein level of TRAP1 and impeded its downstream signaling by reduction of cellular succinate levels and destabilization of HIF-1α. The pharmacogenomic biomarkers associated with CVM-1118 were also examined by Whole Genome CRISPR Knock-Out Screening. Two hits (STK11 and NF2) were confirmed with higher sensitivity to the drug in cell knock-down experiments. Biological assays indicate that the mechanism of action of CVM-1118 is via targeting TRAP1 to induce mitochondrial apoptosis, suppress tumor cell growth, and inhibit vasculogenic mimicry formation. Most importantly, the loss-of-function mutations of STK11 and NF2 are potential biomarkers of CVM-1118 which can be applied in the selection of cancer patients for CVM-1118 treatment. CVM-1118 is currently in its Phase 2a clinical development.

A Machine-Learning Approach to Assess Factors Associated With Hospitalization of Children and Youths in Psychiatric Crisis.

OBJECTIVE: The authors used a machine-learning approach to model clinician decision making regarding psychiatric hospitalization of children and youths in crisis and to identify factors associated with the decision to hospitalize. METHODS: Data consisted of 4,786 mobile crisis response team assessments of children and youths, ages 4.0-19.5 years (mean±SD=14.0±2.7 years, 56% female), in Nevada. The sample assessments were split into training and testing data sets. A random-forest machine-learning algorithm was used to identify variables related to the decision to hospitalize a child or youth after the crisis assessment. Results from the training sample were externally validated in the testing sample. RESULTS: The random-forest model had good performance (area under the curve training sample=0.91, testing sample=0.92). Variables found to be important in the decision to hospitalize a child or youth were acute suicidality, followed by poor judgment or decision making, danger to others, impulsivity, runaway behavior, other risky behaviors, nonsuicidal self-injury, psychotic or depressive symptoms, sleep problems, oppositional behavior, poor functioning at home or with peers, depressive or schizophrenia spectrum disorders, and age. CONCLUSIONS: In crisis settings, clinicians were found to mostly focus on acute factors that increased risk for danger to self or others (e.g., suicidality, poor judgment), current psychiatric symptoms (e.g., psychotic symptoms), and functioning (e.g., poor home functioning, problems with peer relationships) when deciding whether to hospitalize or stabilize a child or youth. To reduce psychiatric hospitalization, community-based services should target interventions to address these important factors associated with the need for a higher level of care among youths in psychiatric crisis.

Neurobiological Markers for Predicting Treatment Response in Patients with Bipolar Disorder.

Predictive neurobiological markers for prognosis are essential but underemphasized for patients with bipolar disorder (BD), a neuroprogressive disorder. Hence, we developed models for predicting symptom and functioning changes. Sixty-one patients with BD were recruited and assessed using the Young Mania Rating Scale (YMRS), Montgomery−Åsberg Depression Rating Scale (MADRS), Positive and Negative Syndrome Scale (PANSS), UKU Side Effect Rating Scale (UKU), Personal and Social Performance Scale (PSP), and Global Assessment of Functioning scale both at baseline and after 1-year follow-up. The models for predicting the changes in symptom and functioning scores were trained using data on the brain morphology, functional connectivity, and cytokines collected at baseline. The correlation between the predicted and actual changes in the YMRS, MADRS, PANSS, and UKU scores was higher than 0.86 (q < 0.05). Connections from subcortical and cerebellar regions were considered for predicting the changes in the YMRS, MADRS, and UKU scores. Moreover, connections of the motor network were considered for predicting the changes in the YMRS and MADRS scores. The neurobiological markers for predicting treatment-response symptoms and functioning changes were consistent with the neuropathology of BD and with the differences found between treatment responders and nonresponders.

Fluorescent aptasensor based on conformational switch-induced hybridization for facile detection of ß-amyloid oligomers.

Aß oligomers (AßO) are a dominant biomarker for early Alzheimer's disease diagnosis. A fluorescent aptasensor coupled with conformational switch-induced hybridization was established to detect AßO. The fluorescent aptasensor is based on the interaction of fluorophore-labeled AßO-specific aptamer (FAM-Apt) against its partly complementary DNA sequence on the surface of magnetic beads (cDNA-MBs). Once the FAM-Apt binds to AßO, the conformational switch of FAM-Apt increases the tendency to be captured by cDNA-MBs. This causes a descending fluorescence of supernatant, which can be utilized to determine the levels of AßO. Thus, the base-pair matching above 12 between FAM-Apt and cDNA-MBs with increasing hybridizing free energies reached the ascending fluorescent signal equilibrium. The optimized aptasensor showed linearity from 1.7 ng mL-1 to 85.1 (R = 0.9977) with good recoveries (79.27-109.17%) in plasma. Furthermore, the established aptasensor possesses rational selectivity in the presence of monomeric Aß, fibrotic Aß, and interferences. Therefore, the developed aptasensor is capable of quantifying AßO in human plasma and possesses the potential to apply in clinical cases.

Recent progress in nanomaterial-functionalized membranes for removal of pollutants.

Membrane technology has gained tremendous attention for removing pollutants from wastewater, mainly due to their affordable capital cost, miniature equipment size, low energy consumption, and high efficiency even for the pollutants present in lower concentrations. In this paper, we review the literature to summarize the progress of nanomaterial-modified membranes for wastewater treatment applications. Introduction of nanomaterial in the polymeric matrix influences membrane properties such as surface roughness, hydrophobicity, porosity, and fouling resistance. This review also covers the importance of functionalization strategies to prepare thin-film nanocomposite hybrid membranes and their effect on eliminating pollutants. Systematic discussion regarding the impact of the nanomaterials incorporated within membrane, toward the recovery of various pollutants such as metal ions, organic compounds, dyes, and microbes. Successful examples are provided to show the potential of nanomaterial-functionalized membranes for regeneration of wastewater. In the end, future prospects are discussed to develop nanomaterial-based membrane technology.

Quantitative and amplification-free detection of SOCS-1 CpG methylation percentage analyses in gastric cancer by fiber optic nanoplasmonic biosensor.

A new innovative approach is essential for early and effective diagnosis of gastric cancer, using promoter hypermethylation of the tumor suppressor, SOCS-1, that is frequently inactivated in human cancers. We have developed an amplification-free fiber optic nanoplasmonic biosensor for detecting DNA methylation of the SOCS-1 human genome. The method is based on the fiber optic nanogold-linked sorbent assay of PCR-free DNA from human gastric tumor tissue and cell lines. We designed a specific DNA probe fabricated on the fiber core surface while the other probe is bioconjugated with gold nanoparticles in free form to allow percentage determination and differentiating the methylated and unmethylated cell lines, further demonstrating the SOCS-1 methylation occurs in cancer patients but not in normal cell lines. The observed detection limit is 0.81 fM for methylated DNA, and the detection time is within 15 min. In addition, our data were significantly correlated to the data obtained from PCR-based pyrosequencing, and yet with superior accuracy. Hence our results provide new insight to the quantitative evaluation of methylation status of the human genome and can act as an alternative to PCR with a great potential.

Predictors of Employment Status for Persons with Bipolar Disorder.

Bipolar disorder is characterized by manic and depressive episodes and can be a lifetime condition. Bipolar disorder has been found to be associated with various types of disabilities, including low employment rate and high dependence on public aid. The purpose of this study is to identify factors related to being employed for persons with bipolar disorder. Nine thousand eight hundred and eighty-six subjects with bipolar disorder were collected between July of 2012 and November of 2013 and retrieved from Taiwan national disability database on May of 2014. The mean age of the sample is 45.41 (SD = 10.5), with 64% as female. Logistic regression was used to examine the log odds of the predictive variables on outcome of employment. A Receiver Operating Characteristics analysis was applied to locate the cutoff score of World Health Organization Disability Assessment Schedule 2.0 for being employed. All demographic variables were found to be significantly correlated with employment status among subjects. The Receiver Operating Characteristics results revealed that those subjects whose scores were below 33.57 had about a four-fold higher probability of being in employment than those whose scores were above 33.57. The result provides insights into future research effort and intervention design aimed at helping persons with bipolar disorder to obtain gainful employment.

Determination of 13-cis-Retinoic Acid and Its Metabolites in Plasma by Micellar Electrokinetic Chromatography Using Cyclodextrin-Assisted Sweeping for Sample Preconcentration.

The online preconcentration technique, cyclodextrin-assisted sweeping (CD-sweeping), coupled with micellar electrokinetic chromatography (MEKC) was established to determine 13-cis-retinoic acid (13-cis-RA), all-trans-retinoic acid (all-trans-RA) and 4-oxo-13-cis-retinoic acid (4-oxo-13-cis-RA) in human plasma. A CD-sweeping buffer (45 mM borate (pH 9.2), containing 80 mM sodium dodecyl sulfate (SDS) and 22 mM hydroxypropyl ß-CD (HP-ß-CD) was introduced into the capillary and, then, the sample dissolved in 70 mM borate (pH 9.2): methanol = 9:1 (v/v) was injected into capillary by pressure. The separation voltage was 23 kV. Compared to the conventional cyclodextrin-micellar electrokinetic chromatography (CD-MEKC) method, the new technique achieved 224-257-fold sensitivity enrichment of analytes. The limits of detection of 13-cis-RA, all-trans-RA were 1 ng/mL, whereas that of 4-oxo-13-cis-RA was 25 ng/mL in plasma. The linear ranges of 13-cis-RA, all-trans-RA were between 15 and 1000 ng/mL, whereas that of 4-oxo-13-cis-RA was between 75 and 1500 ng/mL. The coefficient of correlation between the concentration of analytes and peak area ratio of analytes and internal standard (2, 4-dihydroxy-benzophenone) for intra-day (n = 3) and inter-day (n = 5) analyses were both greater than 0.999. The optimized experimental conditions were successfully applied to determine 13-cis-retinoic acid and its metabolites in plasma samples from a patient during the administration of 13-cis-RA for treating acne.

Dual-functional gold-iron oxide core-satellite hybrid nanoparticles for sensitivity enhancement in biosensors via nanoplasmonic and preconcentration effects.

A common strategy to improve the sensitivity of a biosensor for the detection of a low abundance analyte is to preconcentrate the analyte molecules before detection. A dual-functional gold-iron oxide core-satellite hybrid nanoparticle structure is proposed in this work to overcome the drawbacks of traditional sample pretreatment methods and the methods using non-magnetic nanomaterials for sample pretreatment. The new dual-functional hybrid nanoparticle structure can simultaneously serve as a signal reporter of a biorecognition event and a preconcentrator of a target at an extremely low concentration in a nanoplasmonic biosensor. By utilizing a fiber optic nanogold-linked sorbent assay in the fiber optic particle plasmon resonance (FOPPR) biosensor and an arbitrary DNA sequence as a target, we have demonstrated that the use of the new hybrid nanoparticle structure with magnetic preconcentration improves the limit of detection (LOD) for the DNA by 18 times as compared to the same method without magnetic preconcentration, so that the LOD for detecting the DNA can be as low as 2.6 fM. The new hybrid nanoparticle structure is easy to prepare and its use in the high-sensitivity and low-cost FOPPR biosensor provides vast opportunities in point-of-care applications.

Identifying subtypes of bipolar disorder based on clinical and neurobiological characteristics.

The ability to classify patients with bipolar disorder (BD) is restricted by their heterogeneity, which limits the understanding of their neuropathology. Therefore, we aimed to investigate clinically discernible and neurobiologically distinguishable BD subtypes. T1-weighted and resting-state functional magnetic resonance images of 112 patients with BD were obtained, and patients were segregated according to diagnostic subtype (i.e., types I and II) and clinical patterns, including the number of episodes and hospitalizations and history of suicide and psychosis. For each clinical pattern, fewer and more occurrences subgroups and types I and II were classified through nested cross-validation for robust performance, with minimum redundancy and maximum relevance, in feature selection. To assess the proportion of variance in cognitive performance explained by the neurobiological markers, multiple linear regression between verbal memory and the selected features was conducted. Satisfactory performance (mean accuracy, 73.60%) in classifying patients with a high or low number of episodes was attained through functional connectivity, mostly from default-mode and motor networks. Moreover, these neurobiological markers explained 62% of the variance in verbal memory. The number of episodes is a potentially critical aspect of the neuropathology of BD. Neurobiological markers can help identify BD neuroprogression.

Determination of quetiapine and its metabolites in plasma by field-enhanced sample stacking.

Quetiapine is an atypical antipsychotic drug that can be used to treat mental disorders, including schizophrenia, bipolar disorder and Alzheimer's disease. Quetiapine is mainly converted into the active metabolites of norquetiapine and 7-hydroxyquetiapine by the liver enzymes CYP3A4 and CYP2D6. In this study, liquid-liquid extraction (LLE) was used as a sample pretreatment method to eliminate interferences in plasma. tert-Butyl methyl ether was chosen as the extraction solvent. Field-enhanced sample injection (FESS), an online preconcentration technique, was used to analyze quetiapine and its metabolites norquetiapine and 7-hydroxyquetiapine in plasma. The optimal separation condition was 120 mM phosphate (pH 4.0) containing 0.005% (w/v) polyvinyl pyrrolidone and 40% (v/v) methanol. The methanol plug was 0.3 psi for 6 s, the sample was electrokinetic injection by 10 kV for 60 s at positive polarity, and the separation voltage was set at 26 kV. In this experiment, quetiapine, norquetiapine and 7-hydroxyquetiapine were successfully extracted from plasma by the LLE method and stacking and separated by FESS within 15 min. The limits of detection (S/N = 3) of quetiapine, norquetiapine and 7-hydroxyquetiapine were 0.25 ng/mL, 0.50 ng/mL and 1.00 ng/mL, respectively. The linear ranges of quetiapine, norquetiapine and 7-hydroxyquetiapine were 3-120 ng/mL and the correlation coefficients were 0.999. Compared with that of the traditional capillary zone electrophoresis method, the sensitivity enrichment of analytes was 463-835-fold. The optimal experimental conditions were successfully applied to the analysis of plasma samples from patients taking quetiapine for the treatment of schizophrenia.

Network-Specific Corticothalamic Dysconnection in Attention-Deficit Hyperactivity Disorder.

BACKGROUND: Functional connectivity (FC) is believed to be abnormal in attention-deficit hyperactivity disorder (ADHD). Most studies have focused on frontostriatal systems, and the role of the thalamic network in ADHD remains unclear. The current study used FC magnetic resonance imaging (fcMRI) to explore corticothalamic network properties and correlated network dysconnection with ADHD symptom severity. METHODS: Eighteen adolescents with ADHD and 16 healthy controls aged 12 to 17 years underwent resting functional MRI scans, clinical evaluations, and 2 parent rating scales, namely the Swanson, Nolan, and Pelham IV scale and the Child Behavior Checklist. Six a priori cortical regions of interest were used to derive 6 networks: the dorsal default mode network, frontoparietal network, cingulo-opercular network (CON), primary sensorimotor network (SM1), primary auditory network, and primary visual network (V1). The corticothalamic connectivity for each network was calculated for each participant and then compared between the groups. We also compared the 2 scales with the network connectivity. RESULTS: The corticothalamic connectivity within the CON was significantly reduced (p < 0.05) among adolescents with ADHD compared with the controls. The corticothalamic dysconnection within the CON, SM1, and V1 networks negatively correlated with ADHD symptom severity. CONCLUSION: This network analysis indicates that corticothalamic dysconnection in ADHD involves the CON, SM1, and V1 networks and relates to symptom severity. The findings provide evidence of dysfunctional thalamus-related networks in ADHD.

Using Minimal-Redundant and Maximal-Relevant Whole-Brain Functional Connectivity to Classify Bipolar Disorder.

BACKGROUND: A number of mental illness is often re-diagnosed to be bipolar disorder (BD). Furthermore, the prefronto-limbic-striatal regions seem to be associated with the main dysconnectivity of BD. Functional connectivity is potentially an appropriate objective neurobiological marker that can assist with BD diagnosis. METHODS: Health controls (HC; n = 173) and patients with BD who had been diagnosed by experienced physicians (n = 192) were separated into 10-folds, namely, a ninefold training set and a onefold testing set. The classification involved feature selection of the training set using minimum redundancy/maximum relevance. Support vector machine was used for training. The classification was repeated 10 times until each fold had been used as the testing set. RESULTS: The mean accuracy of the 10 testing sets was 76.25%, and the area under the curve was 0.840. The selected functional within-network/between-network connectivity was mainly in the subcortical/cerebellar regions and the frontoparietal network. Furthermore, similarity within the BD patients, calculated by the cosine distance between two functional connectivity matrices, was smaller than between groups before feature selection and greater than between groups after the feature selection. LIMITATIONS: The major limitations were that all the BD patients were receiving medication and that no independent dataset was included. CONCLUSION: Our approach effectively separates a relatively large group of BD patients from HCs. This was done by selecting functional connectivity, which was more similar within BD patients, and also seems to be related to the neuropathological factors associated with BD.

Resistin enhances IL-1ß and TNF-α expression in human osteoarthritis synovial fibroblasts by inhibiting miR-149 expression via the MEK and ERK pathways.

Resistin is a cysteine-rich adipokine that promotes the release of inflammatory cytokines, particularly interleukin 1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α), which are critical pro-inflammatory mediators in osteoarthritis (OA) pathogenesis. We describe evidence of significantly higher levels of resistin, IL-1ß, and TNF-α expression in OA knee synovial tissue compared with that from non-OA knees. Resistin-induced enhancement of IL-1ß and TNF-α expression in human OA synovial fibroblasts (OASFs) were attenuated by MEK and ERK inhibitors, as well as their respective siRNAs. Our data reveal that resistin enhances the expression of TNF-α and IL-1ß in OASFs by inhibiting miR-149 expression via MEK and ERK signaling. Our findings elucidate the inter-relationships between resistin and pro-inflammatory mediators during OA pathogenesis and could help to facilitate the development of synovium-targeted therapy in OA.