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Previous studies have investigated the role of inflammatory markers in suicidality of patients with major depressive disorder (MDD) or panic disorder (PD). However, few studies have investigated associations between serum inflammatory cytokine levels and suicidality. We hypothesized that MDD and PD status might be significantly associated with serum inflammatory cytokines and that we could predict levels of improvement in suicide ideation intensity using serum inflammatory biomarkers in patients with MDD and PD. For this study, 41 patients with MDD, 52 patients with PD, and 59 healthy control (HC) subjects were enrolled. Psychological measurements and serum inflammatory markers such as interleukin (IL) −6, −10, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and C reactive protein (CRP) were examined. A total of five visits were completed during 12 weeks. After controlling for confounding factors, log-transformed IL-6 (ln_IL-6) at baseline (MDD: 0.297 ± 0.626; PD: 0.342 ± 0.723; HC: −0.121 ± 0.858; p = 0.007, >0.0017, 0.05/30) and mean ln_IL-6 (MDD: 0.395 ± 0.550, PD: 0.249 ± 0.544, HC: −0.139 ± 0.622, p = 0.002, >0.0017, 0.05/30) levels were trends towards significantly higher in patients with MDD and PD than in HC. In MDD patients, a higher level of basal ln_TNF-α was a significant predictor of ΔSSI (changes in SSI scores between baseline and week 12) even after controlling for changes of depression symptoms and baseline SSI scores (standardized β = 0.541, p = 0.002 < 0.0028, 0.05/18). In conclusion, we could predict ΔSSI using baseline inflammatory biomarkers for patients with MDD. [ABSTRACT FROM AUTHOR]

• Mitochondrial dysfunction was observed in the PPA-treated SH-SY5Y cells. • Mitochondrial biogenesis-related protein expression was increased by PPA treatment. • PPA treatment induce ASCL1 and LFNG gene expression change. Studies in animal models have shown that the short-chain fatty acid, propionic acid (PPA), interferes with mitochondrial metabolism leading to mitochondrial dysfunction and behavioral abnormalities. The aim of this study was to investigate the effects of PPA on mitochondrial function and gene expression in neuronal cells. SH-SY5Y cells and normal human neural progenitor (NHNP) cells were exposed to 1, 5 mM PPA for 4 or 24 h and we found that the mitochondrial potential measured in SH-SY5Y cells decreased in a dose-dependent manner after PPA treatment. Electron microscopy analysis revealed that the size of the mitochondria was significantly reduced following PPA treatment. A dose-dependent increase in the mitochondrial DNA copy number was observed in the PPA-treated cells. The expression of the mitochondrial biogenesis-related proteins PGC-1α, TFAM, SIRT3, and COX4 was significantly increased after PPA treatment. Transcriptome analysis revealed that mRNA expression in the notch signaling-related genes ASCL1 and LFNG changed after PPA treatment and the positive correlated protein expression changes were also observed. These results revealed that PPA treatment may affect neurodevelopment by altering mitochondrial function and notch signaling-related gene expression. [ABSTRACT FROM AUTHOR]

Background: Heart Rate Variability (HRV) parameters have been used to evaluate the autonomic nervous system. We hypothesized that patients with major depressive disorder (MDD) and panic disorder (PD) showed different HRV profiles compared to healthy controls. We also hypothesized that we could predict the responder groups in the MDD and PD patients, using differences in HRV indices between the stress and rest phases.Methods: 28 MDD patients and 29 PD patients were followed for 12 weeks, and we also followed 39 healthy control subjects. We measured HRV parameters at the rest, stress, and recovery phases.Results: Patients with MDD and PD demonstrated lower pNN50 than controls during the stress (F = 7.49, p = 0.001), and recovery phases (F = 9.43, p = 0.0001). Patients with MDD and PD also showed higher LF/HF ratio than controls during the stress phase (F = 6.15, p = 0.002). Responders in the PD group presented a lower level of LF/HF ratio during the stress phase compared to non-responders (F = 10.14, p = 0.002), while responders in the MDD group showed a lower level of heart rate during all three phases, compared to non-responders. Additionally, we could predict treatment response in patients with MDD using ΔLF/HF ratio (OR: 1.33, 95% CI = 1.07-1.65, p = 0.011) and ΔpNN50 (OR: 1.49, 95% CI 1.09-1.77, p = 0.014).Conclusion: The changes of HRV parameters of pNN50 and LF/HF ratio between the stress and recovery phase may be clinical markers of predictors of treatment responsiveness in MDD and PD patients. [ABSTRACT FROM AUTHOR]

• FOXO3 induction by acute valproate exposure was confirmed at in vivo model in juvenile male hippocampus only. • Proneural gene expression, ASCL1 and NGN2, were upregulated by FOXO3 down expression in FOXO3 siRNA treated PC12 cells. • Mitochondria biogenesis related gene expressions were regulated by FOXO3 expression in FOXO3 siRNA treated PC12 cells. Valproic acid (VPA), an anticonvulsant and mood stabilizer, may affect Notch signaling and mitochondrial function. In a previous study, acute VPA exposure induced increased expression of FOXO3, a transcription factor that shares common targets with pro-neuronal ASCL1. In this study, intraperitoneal acute VPA (400 mg/kg) administration in 4-week-old mice increased and decreased FOXO3 and ASCL1 expression, respectively, in the hippocampus, associated with sex-based differences. Treatment of Foxo3 siRNA increased the mRNA expression levels of Ascl1, Ngn2, Hes6, and Notch1 in PC12 cells. Furthermore, VPA exposure induced significant expression changes of mitochondria-related genes, including COX4 and SIRT1 , in hippocampal tissues, associated with sex-based differences. This study suggests that acute VPA exposure differently affects proneural gene expression via FOXO3 induction in the hippocampus based on sex. [ABSTRACT FROM AUTHOR]

• Higher pre-treatment leptin is associated with better treatment response on panic symptoms in MDD patients. • Higher pre-treatment IL-6 is associated with worse treatment response on panic symptoms in PD patients. • Individualized predictive biomarker research is neccessary for clinical practice. Peripheral biomarkers have been studied to predict treatment response of panic symptoms. We hypothesized that depressive disorder (MDD) vs. panic disorder (PD) would exhibit different peripheral biomarkers, and their correlation with severity of panic attacks (PA) would also differ. Forty-one MDD patients, 52 PD patients, and 59 healthy controls were followed for 12 weeks. We measured peripheral biomarkers along with the Panic Disorder Severity Scale (PDSS) at each visit—pre-treatment, 2, 4, 8, and 12 weeks on a regular schedule. Peripheral biomarkers including serum cytokines, plasma and serum brain-derived neurotrophic factor (BDNF), leptin, adiponectin, and C-reactive protein (CRP) were quantified using enzyme-linked immunosorbent assay (ELISA). Patients with MDD and PD demonstrated significantly higher levels of pre-treatment IL-6 compared to controls, but no differences were seen in plasma and serum BDNF, leptin, adiponectin, and CRP. Pre-treatment leptin showed a significant clinical correlation with reduction of panic symptoms in MDD patients at visit 5 (p = 0.011), whereas pre-treatment IL-6 showed a negative correlation with panic symptom reduction in PD patients (p = 0.022). An improvement in three panic-related items was observed to be positively correlated with pre-treatment leptin in MDD patients: distress during PA, anticipatory anxiety, and occupational interference. Higher pre-treatment leptin was associated with better response to treatment regarding panic symptoms in patients with MDD, while higher IL-6 was associated with worse response regarding panic symptoms in PD patients. Different predictive peripheral biomarkers observed in MDD and PD suggest the need for establishing individualized predictive biomarkers, even in cases of similar symptoms observed in different disorders. [ABSTRACT FROM AUTHOR]

Herein, we developed a facile one-pot approach to prepare amphiphilic aggregation-induced emission (AIE)-active hyperbranched fluorescent nanoparticles with a core–shell structure. This was conducted via the addition reaction between tetraphenylethylene (TPE)-OH, isophorone diisocyanate, and hyperbranched polyglycidol (HPG) using a one-pot method. The resultant AIE-active hyperbranched polymer structure was characterized by 1H nuclear magnetic resonance and Fourier-transform infrared spectroscopy. The amphiphilic AIE-active polymer was prone to self-assemble in an aqueous solution to form core–shell type nanoparticles with a TPE core and hydroxyl groups on the core surface. The self-assembly of nanoparticles in the aqueous solution was characterized using dynamic light scattering, ultraviolet–visible spectroscopy, fluorescence spectroscopy, and transmission electron microscopy. Aggregation behavior of TPE-HPG polymer in water and diethyl ether was studied by dissipative particle dynamics simulation. Furthermore, these TPE-HPG nanoparticles exhibited a strong blue luminescence in the aqueous solution due to the aggregation of the AIE feature of TPE. These polymeric nanoparticles showed high water solubility, good photostability, and biological imaging properties. The cell viability assay and confocal microscopy imaging results suggested that the TPE-HPG fluorescent polymeric organic nanoparticles (FPNs) have low cytotoxicity and excellent biocompatibility. Thus, TPE-HPG FPNs are excellent candidates for biomedical applications. Image 1 • Aggregation-induced emission (AIE)-active hyperbranched polymer is synthesized. • The amphiphilic polymer is self-assembled to form AIE-active nanoparticles (NPs). • The AIE-active NPs show excellent water dispersibility and biocompatibility for bioimaging applications. [ABSTRACT FROM AUTHOR]

Abstract: Background: The genetic factors that determine the heterogeneity of cognitive impairment in Alzheimer's disease (AD) patients have been rarely reported. We aimed to investigate the association between top hits of genome-wide association studies (GWAS) and specific cognitive domains in AD patients. Methods: We investigated 86 single nucleotide polymorphisms (SNPs) selected from 12 genes (ABCA7, APOE, BIN1, CD2AP, CD33, CLU, CR1, EPHA1, LRAT, MS4A6A, PCDH11X, and PICALM) based on results of the recent GWAS and genotyped in 211 AD cases. We also analyzed results of comprehensive neuropsychological evaluations in all cases. We performed multiple regression analyses. Results: There were four significant associations between genotypes and phenotypes of AD patients: CR1 SNP rs11803956 correlated with Mini-Mental State Examination (MMSE) score (β=1.718, Pcorrected =0.002); ABCA7 SNP rs3752232 correlated with Rey Complex Figure Test (RCFT) copy score (β=−6.861, Pcorrected =0.013); APOE SNP rs2075650 correlated with the percentile of RCFT copy score (β=14.005, Pcorrected =0.021) and the percentile of total score in phonemic fluency (β=11.052, Pcorrected =0.035). Conclusion: Our results suggest that CR1, ABCA7, and APOE correlate with specific aspects of cognitive impairments in AD patients. [Copyright &y& Elsevier]

Highlights: [•] We investigated brain MD changes in Parkinson's disease patients. [•] MD changes in corticofugal tract, cingulum and other white matter tracts in PD. [•] MD changes in left putamen, caudate, pallidum and thalamus in PD [Copyright &y& Elsevier]