rTMS Induces Brain Functional and Structural Alternations in Schizophrenia Patient With Auditory Verbal Hallucination

BackgroundLow-frequency transcranial magnetic stimulation (rTMS) over the left temporoparietal cortex reduces the auditory verbal hallucination (AVH) in schizophrenia. However, the underlying neural basis of the rTMS treatment effect for schizophrenia remains not well understood. This study investigates the rTMS induced brain functional and structural alternations and their associations with clinical as well as neurocognitive profiles in schizophrenia patients with AVH.MethodsThirty schizophrenia patients with AVH and thirty-three matched healthy controls were enrolled. The patients were administered by 15 days of 1 Hz rTMS delivering to the left temporoparietal junction (TPJ) area. Clinical symptoms and neurocognitive measurements were assessed at pre- and post-rTMS treatment. The functional (amplitude of low-frequency fluctuation, ALFF) and structural (gray matter volume, GMV) alternations were compared, and they were then used to related to the clinical and neurocognitive measurements after rTMS treatment.ResultsThe results showed that the positive symptoms, including AVH, were relieved, and certain neurocognitive measurements, including visual learning (VisLearn) and verbal learning (VerbLearn), were improved after the rTMS treatment in the patient group. Furthermore, the rTMS treatment induced brain functional and structural alternations in patients, such as enhanced ALFF in the left superior frontal gyrus and larger GMV in the right inferior temporal cortex. The baseline ALFF and GMV values in certain brain areas (e.g., the inferior parietal lobule and superior temporal gyrus) could be associated with the clinical symptoms (e.g., positive symptoms) and neurocognitive performances (e.g., VerbLearn and VisLearn) after rTMS treatment in patients.ConclusionThe low-frequency rTMS over the left TPJ area is an efficacious treatment for schizophrenia patients with AVH and could selectively modulate the neural basis underlying psychiatric symptoms and neurocognitive domains in schizophrenia

Protocol development for discovery of angiogenesis inhibitors via automated methods using zebrafish.

Their optical clarity as larvae and embryos, small size, and high fecundity make zebrafish ideal for whole animal high throughput screening. A high-throughput drug discovery platform (HTP) has been built to perform fully automated screens of compound libraries with zebrafish embryos. A Tg(kdrl:EGFP) line, marking endothelial cell cytoplasm, was used in this work to help develop protocols and functional algorithms for the system, with the intent of screening for angiogenesis inhibitors. Indirubin 3' Monoxime (I3M), a known angiogenesis inhibitor, was used at various concentrations to validate the protocols. Consistent with previous studies, a dose dependant inhibitory effect of I3M on angiogenesis was confirmed. The methods and protocols developed here could significantly increase the throughput of drug screens, while limiting human errors. These methods are expected to facilitate the discovery of novel anti-angiogenesis compounds and can be adapted for many other applications in which samples have a good fluorescent signal

Mental health status and related influencing factors in patients with COVID-19

Abstract Background The outbreak of the Corona Virus Disease 2019 (COVID-2019) has resulted in a significant number of diagnosed patients requiring treatment in designated hospitals. However, limited evidence exists regarding the prevalence of mental health problems and associated psychological factors in COVID-19 patients. Objectives This study investigated the prevalence rates of anxiety, depression, and insomnia among COVID-19 patients, as well as explored the associations between these mental health problems and psychological factors. Methods A cross-sectional study was conducted among 387 COVID-19 patients in a designated shelter hospital. Online measures were used to assess anxiety, depression, insomnia, social support, coping styles, and emotional regulation. Data were analyzed to determine the prevalence rates of mental health problems and examine the associations between these problems and the psychological factors. Results The results revealed high prevalence rates of anxiety (21.80%), depression (49.0%), and insomnia (63.70%) among COVID-19 patients. Objective social support scores and positive coping style scores were significantly associated with lower levels of anxiety, depression, and insomnia, respectively. Conversely, high negative coping style scores, higher education level, and self-perceived illness severity, were significantly related to higher levels of anxiety, depression, or insomnia symptoms. Emotional regulation scores did not show a significant association with any of the examined mental health problems. Conclusions These findings have implications for guiding psychological interventions tailored to COVID-19 patients in future outbreaks. By targeting social support and promoting adaptive coping strategies, psychological interventions can address the psychological distress experienced by COVID-19 patients

Table_1_The alternations of nucleus accumbent in schizophrenia patients with auditory verbal hallucinations during low-frequency rTMS treatment.docx

Low-frequency repetitive transcranial magnetic stimulation (rTMS) has been shown to reduce the severity of auditory verbal hallucinations (AVH) and induce beneficial functional and structural alternations of the brain in schizophrenia patients with AVH. The nucleus accumbens (NAcc) as an important component of the ventral striatum is implicated with the pathology in AVH. However, the induced characteristic patterns of NAcc by low-frequency rTMS in schizophrenia with AVH are seldom explored. We investigated the functional and structural characteristic patterns of NAcc by using seed-based functional connectivity (FC) analysis and gray matter volume (GMV) measurement in schizophrenia patients with AVH during 1 Hz rTMS treatment. Although low-frequency rTMS treatment did not affect the volumetric changes of NAcc, the abnormal FC patterns of NAcc, including increased FC of NAcc with the temporal lobes and decreased FC of NAcc with the frontal cortices in the pretreatment patients compared to healthy controls, were normalized or reversed after treatment. These FC changes were associated with improvements in clinical symptoms and neurocognitive functions. Our findings may extend our understanding of the NAcc in the pathology of schizophrenia with AVH and might be a biomarker of clinical effect for low-frequency rTMS treatment in schizophrenia.</p

DACT1 Involvement in the Cytoskeletal Arrangement of Cardiomyocytes in Atrial Fibrillation by Regulating Cx43

Abstract Objective: To determine the role of the dishevelled binding antagonist of beta catenin 1 (DACT1) in the cytoskeletal arrangement of cardiomyocytes in atrial fibrillation (AF). Methods: The DACT1 expression and its associations with the degree of fibrosis and β-catenin in valvular disease patients were analyzed by immunohistochemistry and Masson’s staining. DACT1 was overexpressed in the atrial myocyte cell line (HL-1) and the cardiac cell line (H9C2) by adenoviral vectors. Alterations in the fibrous actin (F-actin) content and organization and the expression of β-catenin were detected by flow cytometry, immunofluorescence, and Western blotting. Additionally, the association of DACT1 with gap junctions connexin 43 (Cx43) was detected by immunohistochemistry, immunofluorescence, and Western blotting. Results: Decreased cytoplasmic DACT1 expression in the myocardium was associated with AF (P=0.037) and a high degree of fibrosis (weak vs. strong, P=0.028; weak vs. very strong, P=0.029). A positive association was observed between DACT1 and β-catenin expression in clinical samples (P=0.028, Spearman’s rho=0.408). Furthermore, overexpression of DACT1 in HL-1 and H9C2 cells induced an increase in β-catenin and subsequent partial colocalization of DACT1 and β-catenin. In addition, F-actin content and organization were enhanced. Interestingly, DACT1 was positively correlated with the Cx43 expression in clinical samples (P=0.048, Spearman’s rho=0.370) and changed the Cx43 distribution in cardiac cell lines. Conclusion: DACT1 proved to be a novel AF-related gene by regulating Cx43 via cytoskeletal organization induced by β-catenin accumulation in cardiomyocytes. DACT1 could thus serve as a potential therapeutic marker for AF

Mesenchymal stem cell attenuates spinal cord injury by inhibiting mitochondrial quality control-associated neuronal ferroptosis

Ferroptosis is a newly discovered form of iron-dependent oxidative cell death and drives the loss of neurons in spinal cord injury (SCI). Mitochondrial damage is a critical contributor to neuronal death, while mitochondrial quality control (MQC) is an essential process for maintaining mitochondrial homeostasis to promote neuronal survival. However, the role of MQC in neuronal ferroptosis has not been clearly elucidated. Here, we further demonstrate that neurons primarily suffer from ferroptosis in SCI at the single-cell RNA sequencing level. Mechanistically, disordered MQC aggravates ferroptosis through excessive mitochondrial fission and mitophagy. Furthermore, mesenchymal stem cells (MSCs)-mediated mitochondrial transfer restores neuronal mitochondria pool and inhibits ferroptosis through mitochondrial fusion by intercellular tunneling nanotubes. Collectively, these results not only suggest that neuronal ferroptosis is regulated in an MQC-dependent manner, but also fulfill the molecular mechanism by which MSCs attenuate neuronal ferroptosis at the subcellular organelle level. More importantly, it provides a promising clinical translation strategy based on stem cell-mediated mitochondrial therapy for mitochondria-related central nervous system disorders