Corrigendum: Lower serum insulin-like growth factor 2 level in patients with bipolar disorder is associated with the severity of manic symptoms during manic episodes.

[This corrects the article DOI: 10.3389/fpsyt.2024.1354999.].

Lower serum insulin-like growth factor 2 level in patients with bipolar disorder is associated with the severity of manic symptoms during manic episodes.

Objective: Accumulating evidence has indicated that neurodevelopmental defects may underlie the pathophysiology of bipolar disorder (BD). Insulin-like growth factors (IGFs) are a family of neurotrophic factors that are essential for the survival and development of neurons. The present study aims to investigate whether IGF-2 signaling is implicated in the pathophysiological processes of BD. Method: 50 healthy controls and 78 patients with BD, including 23 patients who diagnosed acute depressive episode and 55 patients who diagnosed acute manic episode, were recruited in this study. The 17-item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale (YMRS) were used to assess the severity of the depressive and manic symptoms, respectively. The serum IGF-2 level was determined by an enzyme-linked immunosorbent assay (ELISA). The Kolmogorov-Smirnov and Mann-Whitney U tests were used for between-group comparisons and spearman analysis was used to analyze correlations. Results: Patients with BD had lower serum IGF-2 levels (66.08 ± 21.22 ng/ml) when compared to healthy controls (88.72 ± 31.55 ng/ml). BD patients were divided into manic episode and depressive episode subgroups. We found that serum IGF-2 levels were reduced in both the mania and depression subgroups (mania: 67.19 ± 21.52 ng/ml, depression: 63.43 ± 20.67 ng/ml; P < 0.001), while no significant difference was observed between two groups (P > 0.05). Spearman correlation analyses revealed that the levels of serum IGF-2 were negatively correlated with the YMRS scores in BD patients (r = -0.522, P < 0.001). Furthermore, IGF-2 was found to be an independent contributor to the severity of symptoms in patients with manic episodes (B = -0.610, t = -5.299, P < 0.001). Conclusion: Lower serum IGF-2 levels were found in BD patients and correlated with the severity of the manic symptoms in these patients during manic episodes. These results suggest that reduced IGF-2 levels might be involved in the pathophysiology of BD, and serum IGF-2 could be a peripheral biomarker for the evaluation of the severity of manic symptoms in BD patients.

The value of CT-based radiomics in predicting hemorrhagic transformation in acute ischemic stroke patients without recanalization therapy.

Objective: The aim of this study is to investigate the clinical value of radiomics based on non-enhanced head CT in the prediction of hemorrhage transformation in acute ischemic stroke (AIS). Materials and methods: A total of 140 patients diagnosed with AIS from January 2015 to August 2022 were enrolled. Radiomic features from infarcted areas on non-enhanced CT images were extracted using ITK-SNAP. The max-relevance and min-redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) were used to select features. The radiomics signature was then constructed by multiple logistic regressions. The clinicoradiomics nomogram was constructed by combining radiomics signature and clinical characteristics. All predictive models were constructed in the training group, and these were verified in the validation group. All models were evaluated with the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: Of the 140 patients, 59 experienced hemorrhagic transformation, while 81 remained stable. The radiomics signature was constructed by 10 radiomics features. The clinicoradiomics nomogram was constructed by combining radiomics signature and atrial fibrillation. The area under the ROC curve (AUCs) of the clinical model, radiomics signature, and clinicoradiomics nomogram for predicting hemorrhagic transformation in the training group were 0.64, 0.86, and 0.86, respectively. The AUCs of the clinical model, radiomics signature, and clinicoradiomics nomogram for predicting hemorrhagic transformation in the validation group were 0.63, 0.90, and 0.90, respectively. The DCA curves showed that the radiomics signature performed well as well as the clinicoradiomics nomogram. The DCA curve showed that the clinical application value of the radiomics signature is similar to that of the clinicoradiomics nomogram. Conclusion: The radiomics signature, constructed without incorporating clinical characteristics, can independently and effectively predict hemorrhagic transformation in AIS patients.

Role of microglial metabolic reprogramming in Parkinson's disease.

Parkinson's disease (PD) is a common age-related neurodegenerative disorder characterized by damage to nigrostriatal dopaminergic neurons. Key pathogenic mechanisms underlying PD include alpha-synuclein misfolding and aggregation, impaired protein clearance, mitochondrial dysfunction, oxidative stress, and neuroinflammation. However, to date, no study has confirmed the specific pathogenesis of PD. Similarly, current PD treatment methods still have shortcomings. Although some emerging therapies have proved effective for PD, the specific mechanism still needs further clarification. Metabolic reprogramming, a term first proposed by Warburg, is applied to the metabolic energy characteristics of tumor cells. Microglia have similar metabolic characteristics. Pro-inflammatory M1 type and anti-inflammatory M2 type are the two types of activated microglia, which exhibit different metabolic patterns in glucose, lipid, amino acid, and iron metabolism. Additionally, mitochondrial dysfunction may be involved in microglial metabolic reprogramming by activating various signaling mechanisms. Functional changes in microglia resulting from metabolic reprogramming can cause changes in the brain microenvironment, thus playing an important role in neuroinflammation or tissue repair. The involvement of microglial metabolic reprogramming in PD pathogenesis has been confirmed. Neuroinflammation and dopaminergic neuronal death can effectively be reduced by inhibiting certain metabolic pathways in M1 microglia or reverting M1 cells to the M2 phenotype. This review summarizes the relationship between microglial metabolic reprogramming and PD and provides strategies for PD treatment.

Stroke risk study based on deep learning-based magnetic resonance imaging carotid plaque automatic segmentation algorithm.

Introduction: The primary factor for cardiovascular disease and upcoming cardiovascular events is atherosclerosis. Recently, carotid plaque texture, as observed on ultrasonography, is varied and difficult to classify with the human eye due to substantial inter-observer variability. High-resolution magnetic resonance (MR) plaque imaging offers naturally superior soft tissue contrasts to computed tomography (CT) and ultrasonography, and combining different contrast weightings may provide more useful information. Radiation freeness and operator independence are two additional benefits of M RI. However, other than preliminary research on MR texture analysis of basilar artery plaque, there is currently no information addressing MR radiomics on the carotid plaque. Methods: For the automatic segmentation of MRI scans to detect carotid plaque for stroke risk assessment, there is a need for a computer-aided autonomous framework to classify MRI scans automatically. We used to detect carotid plaque from MRI scans for stroke risk assessment pre-trained models, fine-tuned them, and adjusted hyperparameters according to our problem. Results: Our trained YOLO V3 model achieved 94.81% accuracy, RCNN achieved 92.53% accuracy, and MobileNet achieved 90.23% in identifying carotid plaque from MRI scans for stroke risk assessment. Our approach will prevent incorrect diagnoses brought on by poor image quality and personal experience. Conclusion: The evaluations in this work have demonstrated that this methodology produces acceptable results for classifying magnetic resonance imaging (MRI) data.

Progress in research on the role of clinical nutrition in treating traumatic brain injury affecting the neurovascular unit.

The neurovascular unit (NVU) is composed of neurons, glial cells, and blood vessels. NVU dysfunction involves the processes of neuroinflammation, and microcirculatory disturbances, as well as neuronal injury after traumatic brain injury (TBI). Traditional anti-inflammatory drugs have limited efficacy in improving the prognosis of TBI. Thus, treatments that target NVU dysfunction may provide a breakthrough. A large number of clinical studies have shown that the nutritional status of patients with TBI was closely related to their conditions and prognoses. Nutrient complexes and complementary therapies for the treatment of TBI are therefore being implemented in many preclinical studies. Importantly, the mechanism of action for this treatment may be related to repair of NVU dysfunction by ensuring adequate omega-3 fatty acids, curcumin, resveratrol, apigenin, vitamins, and minerals. These nutritional supplements hold promise for translation to clinical therapy. In addition, dietary habits also play an important role in the rehabilitation of TBI. Poor dietary habits may worsen the pathology and prognosis of TBI. Adjusting dietary habits, especially with a ketogenic diet, may improve outcomes in patients with TBI. This article discusses the impact of clinical nutrition on NVU dysfunction after TBI, focusing on nutritional complexes and dietary habits.

Recent research progress on metabolic syndrome and risk of Parkinson's disease.

Parkinson's disease (PD) is one of the most widespread neurodegenerative diseases. PD is associated with progressive loss of substantia nigra dopaminergic neurons, including various motor symptoms (e.g., bradykinesia, rigidity, and resting tremor), as well as non-motor symptoms (e.g., cognitive impairment, constipation, fatigue, sleep disturbance, and depression). PD involves multiple biological processes, including mitochondrial or lysosomal dysfunction, oxidative stress, insulin resistance, and neuroinflammation. Metabolic syndrome (MetS), a collection of numerous connected cerebral cardiovascular conditions, is a common and growing public health problem associated with many chronic diseases worldwide. MetS components include central/abdominal obesity, systemic hypertension, diabetes, and atherogenic dyslipidemia. MetS and PD share multiple pathophysiological processes, including insulin resistance, oxidative stress, and chronic inflammation. In recent years, MetS has been linked to an increased risk of PD, according to studies; however, the specific mechanism remains unclear. Researchers also found that some related metabolic therapies are potential therapeutic strategies to prevent and improve PD. This article reviews the epidemiological relationship between components of MetS and the risk of PD and discusses the potentially relevant mechanisms and recent progress of MetS as a risk factor for PD. Furthermore, we conclude that MetS-related therapies are beneficial for the prevention and treatment of PD.

Update on the application of mesenchymal stem cell-derived exosomes in the treatment of Parkinson's disease: A systematic review.

Parkinson's disease (PD) has become the second largest neurodegenerative disease after Alzheimer's disease, and its incidence is increasing year by year. Traditional dopamine replacement therapy and deep brain stimulation can only alleviate the clinical symptoms of patients with PD but cannot cure the disease. In recent years, stem cell therapy has been used to treat neurodegenerative diseases. Many studies have shown that stem cell transplantation has a therapeutic effect on PD. Here, we review recent studies indicating that exosomes derived from mesenchymal stem cells also have the potential to treat PD in animal models, but the exact mechanism remains unclear. This article reviews the mechanisms through which exosomes are involved in intercellular information exchange, promote neuroprotection and freely cross the blood-brain barrier in the treatment of PD. The increase in the incidence of PD and the decline in the quality of life of patients with advanced PD have placed a heavy burden on patients, families and society. Therefore, innovative therapies for PD are urgently needed. Herein, we discuss the mechanisms underlying the effects of exosomes in PD, to provide new insights into the treatment of PD. The main purpose of this article is to explore the therapeutic potential of exosomes derived from mesenchymal stem cells and future research directions for this degenerative disease.

Life extension factor klotho regulates behavioral responses to stress via modulation of GluN2B function in the nucleus accumbens.

Klotho is a life extension factor that has the ability to regulate the function of GluN2B-containing N-methyl-D-aspartate receptors (NMDARs), whose dysfunction in the nucleus accumbens (NAc) underlies critical aspects of the pathophysiology of major depression. Here, we study the functional relevance of klotho in the pathogenesis of depression. A chronic social defeat stress paradigm, in which mice are categorized as either susceptible or unsusceptible based on their performance in a social interaction test, was used in this study. We found that the expression of klotho was largely decreased in the NAc of susceptible mice compared to control or unsusceptible mice. Genetic knockdown of klotho in the NAc induced behavioral alterations relevant to depression in naive mice, while overexpression of klotho produced an antidepressive effect in normal mice and ameliorated the behavioral responses to stress in susceptible mice. Molecularly, knockdown of klotho in the NAc resulted in selective decreases in total and synaptic GluN2B expression that were identical to those in susceptible mice. Elevation of klotho in the NAc reversed the reductions in GluN2B expressions and altered synaptic transmission and spine density in the NAc of susceptible mice. Furthermore, blockade of GluN2B with a specific antagonist abolished the beneficial effects of klotho elevation in susceptible mice. Collectively, we demonstrated that klotho in the NAc modulates behavioral responses to stress by regulating the function of GluN2B-containing NMDARs. These results reveal a novel role for klotho in the pathogenesis of depression, providing new insights into the molecular basis of major depression.

Decreased Plasma Hydrogen Sulfide Level Is Associated With the Severity of Depression in Patients With Depressive Disorder.

Accumulating evidence has suggested a dysfunction of synaptic plasticity in the pathophysiology of depression. Hydrogen sulfide (H2S), an endogenous gasotransmitter that regulates synaptic plasticity, has been demonstrated to contribute to depressive-like behaviors in rodents. The current study investigated the relationship between plasma H2S levels and the depressive symptoms in patients with depression. Forty-seven depressed patients and 51 healthy individuals were recruited in this study. The 17-item Hamilton Depression Rating Scale (HAMD-17) was used to evaluate depressive symptoms for all subjects and the reversed-phase high-performance liquid chromatography (RP-HPLC) was used to measure plasmaH2S levels. We found that plasma H2S levels were significantly lower in patients with depression relative to healthy individuals (P < 0.001). Compared with healthy controls (1.02 ± 0.34 µmol/L), the plasma H2S level significantly decreased in patients with mild depression (0.84 ± 0.28 µmol/L), with moderate depression (0.62 ± 0.21µmol/L), and with severe depression (0.38 ± 0.18 µmol/L). Correlation analysis revealed that plasma H2S levels were significantly negatively correlated with the HAMD-17 scores in patients (r = -0.484, P = 0.001). Multivariate linear regression analysis showed that plasma H2S was an independent contributor to the HAMD-17 score in patients (B = -0.360, t = -2.550, P = 0.015). Collectively, these results suggest that decreased H2S is involved in the pathophysiology of depression, and plasma H2S might be a potential indicator for depression severity.

Flavonoid fisetin reverses impaired hippocampal synaptic plasticity and cognitive function by regulating the function of AMPARs in a male rat model of schizophrenia.

Cognitive deficits are the core feature of schizophrenia and effective treatment strategies are still missing. Previous studies have reported that fisetin promotes long-term potentiation (LTP) and cognitive function in normal rodents and other model animals of neurological diseases. The aim of this study was to assess the effect of fisetin on synaptic plasticity and cognitive deficits caused by a brief disruption of N-methyl-D-aspartate receptors (NMDARs) with dizocilpine (MK-801) during early development in rats. The cognitive performance was examined by the Morris water maze task and a fear conditioning test. Hippocampal synaptic plasticity was investigated by field potential recording. The expression of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) and cognition-related proteins was measured by western blotting. We found that intraperitoneal administration of fisetin rescued hippocampus-dependent spatial and contextual fear memory in MK-801 rats. In parallel with these behavioral results, fisetin treatment in MK-801 rats reversed the impairment of hippocampal LTP. At the molecular level, fisetin treatment selectively increased the phosphorylation and surface expression of AMPA receptor subunit 1 (GluA1) in MK-801-treated rats. Moreover, fisetin restored the phosphorylation levels of calcium-calmodulin-dependent kinaseII (CaMKII), cAMP response element-binding protein (CREB), and the extracellular signal-regulated kinase (ERK1/2) in MK-801-treated rats. Collectively, our findings demonstrate that fisetin treatment can reverse the deficits of hippocampal synaptic plasticity and memory in a male rat model of schizophrenia by restoring the phosphorylation and surface expression of AMPAR GluA1 subunit, suggesting fisetin as a promising therapeutic candidate for schizophrenia-associated cognitive deficits.

Erratum to: Changes of Serum Insulin-like Growth Factor-2 Response to Negative Symptom Improvements in Schizophrenia Patients Treated with Atypical Antipsychotics.

The article "Changes of Serum Insulin-like Growth Factor-2 Response to Negative Symptom Improvements in Schizophrenia Patients Treated with Atypical Antipsychotics", written by Xue-lin CHAO, Shu-zhen JIANG, Jian-wen XIONG, Jin-qiong ZHAN, Bo WEI, Chun-nuan CHEN, Yuan-jian YANG was originally published electronically on the publisher's internet portal on June 2020 without open access. With the author(s)' decision to opt for Open Choice, the copyright of the article is changed to © The Author(s) 2020 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Changes of Serum Insulin-like Growth Factor-2 Response to Negative Symptom Improvements in Schizophrenia Patients Treated with Atypical Antipsychotics.

Accumulating evidence suggests that a disruption of early brain development, in which insulin-like growth factor-2 (IGF-2) has a crucial role, may underlie the pathophysiology of schizophrenia. Our previous study has shown that decreased serum IGF-2 was correlated with the severity of psychopathology in patients with schizophrenia. Here we conducted a prospective observation trial to investigate the effects of atypical antipsychotics on serum IGF-2 level and its relationship with clinical improvements in schizophrenia patients. Thirty-one schizophrenia patients with acute exacerbation and 30 healthy individuals were recruited in this study. Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and serum IGF-2 levels were determined using ELISA. We found that schizophrenia patients with acute exacerbation had lower serum IGF-2 levels than control individuals at baseline (P<0.05). After 2 months of atypical antipsychotic treatment, a significant improvement in each PANSS subscore and total score was observed in patients (all P<0.01), and the serum IGF-2 levels of patients were significantly increased compared with those at baseline (203.13±64.62 vs. 426.99±124.26 ng/mL; t =-5.044, P<0.001). Correlation analysis revealed that the changes of serum IGF-2 levels in patients were significantly correlated with the improvements of negative symptoms (r=-0.522, P=0.006). Collectively, our findings demonstrated changes of serum IGF-2 response to improvements of negative symptoms in schizophrenia patients treated with atypical antipsychotics, suggesting that serum IGF-2 might be a treatment biomarker for schizophrenia.