Lymphocyte antigen 96: A new potential biomarker and immune target in Parkinson's disease.

BACKGROUND: Lymphocyte antigen 96 (LY96) plays an important role in innate immunity and has been reported to be associated with various neurological diseases. However, its role in Parkinson's disease (PD) remains unclear. METHODS: Transcriptome data from a total of 49 patients with PD and 34 healthy controls were downloaded from the Gene Expression Omnibus (GEO) database to analyse the expression pattern of LY96 and its relationship with gene function and immune-related markers. In addition, peripheral blood samples were collected from clinical patients to validate LY96 mRNA expression levels. Finally, an in vitro cell model of PD based on highly differentiated SH-SY5Y cells was constructed, with small interfering RNA-silenced LY96 expression, and LY96 mRNA level, cell viability, flow cytometry, and mitochondrial membrane potential assays were performed. RESULTS: The results of the analyses of the GEO database and clinical samples revealed significantly abnormally high LY96 expression in patients with PD compared with healthy controls. The results of cell experiments showed that inhibiting LY96 expression alleviated adverse cellular effects by increasing cell viability, reducing apoptosis, and reducing oxidative stress. Gene set enrichment analysis showed that LY96 was positively correlated with T1 helper cells, T2 helper cells, neutrophils, natural killer T cells, myeloid-derived suppressor cells, macrophages, and activated CD4 cells, and may participate in PD through natural killer cell-mediated cytotoxicity pathways and extracellular matrix receptor interaction pathways. CONCLUSION: These findings suggested that LY96 might be a novel potential biomarker for PD, and offer insights into its immunoregulatory role.

Clinical findings of hyperechoic substantia nigra in patients with Parkinson's disease.

This study aims to analyse hyperechoic substantia nigra (HSN) characteristics and the correlation of HSN with clinical features and blood biomarkers in patients with Parkinson's disease (PD). Transcranial sonography (TCS) evaluations of the substantia nigra (SN) were performed in 40 healthy controls and 71 patients with PD, including patients with SN hyperechogenicity (SN+) and those with normal SN echogenicity (SN-). Evaluation of motor and non-motor symptoms was assessed by a series of rating scales. The uricase method was used to determine serum uric acid (UA) levels, and enzyme-linked immunosorbent assay (ELISA) was used to measure plasma interleukin (IL)-1ß levels. TCS showed 92.50% specificity and 61.97% sensitivity in differentiating PD patients from controls. The area of SN+ contralateral to the side of initial motor symptoms (SNcontra) was larger than that ipsilateral to the side of initial motor symptoms (SNipsi). The PDSN+ group had lower Argentine Hyposmia Rating Scale (AHRS) scores and UA levels than the PDSN- group. Binary logistic regression analysis revealed that AHRS scores and UA levels could be independent predictors for HSN. The larger SN echogenic area (SNL) sizes positively correlated with plasma IL-1ß levels in PD patients with SN+. The present study provides further evidence of the potential of SN echogenicity as an imaging biomarker for PD diagnosis. PD patients with HSN have more severe non-motor symptoms of hyposmia. HSN in PD patients is related to the mechanism of abnormal iron metabolism and microglial activation.

Increased plasma lipocalin-2 levels are associated with nonmotor symptoms and neuroimaging features in patients with Parkinson's disease.

Lipocalin-2 (LCN2) is essential for the regulation of neuroinflammation and cellular uptake of iron. This study aimed to evaluate plasma LCN2 levels and explore their correlation with clinical and neuroimaging features in Parkinson's disease (PD) patients. Enzyme-linked immunosorbent assay (ELISA) was used to measure plasma LCN2 levels in 120 subjects. Evaluation of motor symptoms and nonmotor symptoms in PD patients was assessed by the associated scales. Voxel-based morphometry (VBM) was used to evaluate brain volume alterations, and quantitative susceptibility mapping (QSM) was used to quantitatively analyze brain iron deposition in 46 PD patients. Plasma LCN2 levels were significantly higher in PD patients than those in healthy controls. LCN2 levels were negatively correlated with Montreal Cognitive Assessment (MoCA) scores, total brain gray matter volume (GMV), and GMV/total intracranial volume (TIV) ratio, but positively correlated with Hamilton Anxiety Rating Scale (HAMD) scores and mean QSM values of the bilateral substantial nigra (SN). Receiver operating characteristic (ROC) curves confirmed that plasma LCN2 levels had good predictive accuracy for PD. The results suggest that plasma LCN2 levels have potential as a biomarker for the diagnosis of PD. LCN2 may be a therapeutic target for neuroinflammation and brain iron deposition.

Whole-brain spatial organization of hippocampal single-neuron projectomes.

Mapping single-neuron projections is essential for understanding brain-wide connectivity and diverse functions of the hippocampus (HIP). Here, we reconstructed 10,100 single-neuron projectomes of mouse HIP and classified 43 projectome subtypes with distinct projection patterns. The number of projection targets and axon-tip distribution depended on the soma location along HIP longitudinal and transverse axes. Many projectome subtypes were enriched in specific HIP subdomains defined by spatial transcriptomic profiles. Furthermore, we delineated comprehensive wiring diagrams for HIP neurons projecting exclusively within the HIP formation (HPF) and for those projecting to both intra- and extra-HPF targets. Bihemispheric projecting neurons generally projected to one pair of homologous targets with ipsilateral preference. These organization principles of single-neuron projectomes provide a structural basis for understanding the function of HIP neurons.

Single-neuron projectomes of mouse paraventricular hypothalamic nucleus oxytocin neurons reveal mutually exclusive projection patterns.

Oxytocin (OXT) plays important roles in autonomic control and behavioral modulation. However, it is unknown how the projection patterns of OXT neurons align with underlying physiological functions. Here, we present the reconstructed single-neuron, whole-brain projectomes of 264 OXT neurons of the mouse paraventricular hypothalamic nucleus (PVH) at submicron resolution. These neurons hierarchically clustered into two groups, with distinct morphological and transcriptional characteristics and mutually exclusive projection patterns. Cluster 1 (177 neurons) axons terminated exclusively in the median eminence (ME) and have few collaterals terminating within hypothalamic regions. By contrast, cluster 2 (87 neurons) sent wide-spread axons to multiple brain regions, but excluding ME. Dendritic arbors of OXT neurons also extended outside of the PVH, suggesting capability to sense signals and modulate target regions. These single-neuron resolution observations reveal distinct OXT subpopulations, provide comprehensive analysis of their morphology, and lay the structural foundation for better understanding the functional heterogeneity of OXT neurons.

Diagnostic value of plasma SIRT1 levels and whole-brain gray matter volume in Parkinson's disease patients with cognitive impairment.

OBJECTIVE: This study was designed to investigate the diagnostic value of plasma SIRT1 levels and whole-brain gray matter (GM) volume in Parkinson's disease (PD) patients with cognitive impairment. METHODS: Automated enzymatic analysis was performed to measure plasma SIRT1 levels in 80 healthy controls and 77 PD patients. Motor symptoms and nonmotor symptoms in PD patients were assessed using the corresponding scales. A Siemens MAGNETOM Prisma 3 T MRI scanner was used to acquire images in 35 of 77 PD patients. RESULTS: Plasma SIRT1 levels in PD patients were lower than those in healthy controls. Plasma SIRT1 levels were negatively correlated with the age, Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) scores, anxiety, depression, excessive daytime sleepiness (EDS), quality of life, and especially cognitive impairment. Thus, it showed that plasma SIRT1 levels were relevant to visuospatial/executive function, memory, and language. Receiver-operating characteristic (ROC) analysis confirmed that plasma SIRT1 levels had good diagnostic accuracy for PD with anxiety and EDS. Furthermore, plasma SIRT1 levels had a significant positive correlation with GM volume in the whole brain, and ROC analysis confirmed that plasma SIRT1 levels and the total GM volume had good diagnostic accuracy for PD with cognitive impairment. CONCLUSIONS: This study showed that plasma SIRT1 levels were correlated with the nonmotor symptoms of anxiety, depression, EDS, and especially cognitive impairment as well as the total GM volume. Furthermore, the combination of plasma SIRT1 levels and the total GM volume had good diagnostic accuracy for PD with cognitive impairment.

Relationship of irisin with disease severity and dopamine uptake in Parkinson's disease patients.

BACKGROUND: This study was designed to investigate the relationship of irisin with the severity of Parkinson's disease (PD) and dopamine (DOPA) uptake in patients with PD and to understand the role of irisin in PD. METHODS: The plasma levels of irisin and α-syn were measured by enzyme-linked immunosorbent assay (ELISA). Motor and nonmotor symptoms were assessed with the relevant scales. DOPA uptake was measured with DOPA positron emission tomography (PET)/magnetic resonance imaging (MRI). RESULTS: The plasma levels of α-syn and irisin in patients with PD gradually increased and decreased, respectively, with the progression of the disease. There was a negative correlation between plasma α-syn and irisin levels in patients with PD. The level of irisin in plasma was negatively correlated with Unified Parkinson's Disease Rating Scale (UPDRS)-III scores and positively correlated with Montreal Cognitive Assessment (MoCA) scores. The striatal/occipital lobe uptake ratios (SORs) of the ipsilateral and contralateral caudate nucleus and anterior and posterior putamen in the high-irisin group were significantly higher than those in the low-irisin group, and irisin levels in the caudate nucleus and anterior and posterior putamen contralateral to the affected limb were lower than those on the ipsilateral side. The level of irisin was positively correlated with the SORs of the ipsilateral and contralateral caudate nucleus and putamen in PD patients. CONCLUSIONS: Irisin plays a neuroprotective role by decreasing the level of α-syn. Irisin is negatively correlated with the severity of motor symptoms and cognitive impairment. More importantly, irisin can improve DOPA uptake in the striatum of patients with PD, especially on the side contralateral to the affected limb.

Structural changes in the retina and serum HMGB1 levels are associated with decreased cognitive function in patients with Parkinson's disease.

BACKGROUND: Cognitive impairment is a serious nonmotor symptom in patients with Parkinson's disease (PD). Currently, there are few studies investigating the relationship of serum markers and retinal structural changes with cognitive function in PD. OBJECTIVE: To investigate the relationship between retinal structural changes, serum high mobility group box-1 (HMGB1) levels and cognitive function and motor symptoms in PD patients. METHODS: Eighty-nine participants, including 47 PD patients and 42 healthy subjects, were enrolled. PD patients were divided into Parkinson's disease with normal cognitive (PD-NC), Parkinson's disease with mild cognitive impairment (PD-MCI), and Parkinson's disease with dementia (PDD) groups. The motor and nonmotor symptoms of PD patients were evaluated with clinical scale. Serum HMGB1 levels were detected by enzyme-linked immunosorbent assay (ELISA), and ganglion cell-inner plexiform layer complex (GCIPL) thickness changes in the macula were quantitatively analyzed by swept source optical coherence tomography (SS-OCT) in all patients. RESULTS: Compared with the control group, the macular GCIPL (t = -2.308, P = 0.023) was thinner and serum HMGB1 (z = -2.285, P = 0.022) was increased in PD patients. Macular GCIPL thickness in patients with PD-MCI and PDD were significantly lower than that in PD-NC patients, but there were no significant difference between the PD-MCI and PDD groups. Serum HMGB1 levels in patients with PD-MCI and PDD were significantly higher than those in PD-NC patients, and serum HMGB1 levels in PDD patients were higher than those in PD-MCI patients. Correlation analysis showed that serum HMGB1 levels in PD patients were positively correlated with disease duration, HY stage, UPDRS-I score, UPDRS-III score, and UPDRS total score and negatively correlated with MOCA score. Macular GCIPL thickness was negatively correlated with HY stage and positively correlated with MOCA score, and macular GCIPL thickness was negatively correlated with serum HMGB1 level. Logistic regression analysis showed that elevated serum HMGB1 level, thinner macular GCIPL thickness, and higher HY stage were independent risk factors for Parkinson's disease with cognitive impairment (PD-CI). The areas under the receiver operating characteristic curve (AUC) for the serum HMGB1 level and macular GCIPL thickness-based diagnosis of PD-MCI, PDD and PD-CI based on in patients with PD were 0.786 and 0.825, 0.915 and 0.856, 0.852 and 0.841, respectively. The AUC for the diagnosis of PD-MCI, PDD and PD-CI with serum HMGB1 level and GCIPL thickness combined were 0.869, 0.967 and 0.916, respectively. CONCLUSION: The macular GCIPL thickness and serum HMGB1 level are potential markers of cognitive impairment in PD patients, and their combination can significantly improve the accuracy of the diagnosis of cognitive impairment in PD.

An atlas of itch-associated neural dynamics in the mouse brain.

The itch-scratching cycle is mediated by neural dynamics in the brain. However, our understanding of the neural dynamics during this cycle remains limited. In this study, we examine the neural dynamics of 126 mouse brain areas by measuring the calcium signal using fiber photometry. We present numerous response patterns in the mouse brain during the itch-scratching cycle. Interestingly, we find that a group of brain areas exhibit activation only at the end of histamine-induced scratching behavior. Additionally, several brain areas exhibit transient activation at the onset of scratching induced by chloroquine. Both histamine- and chloroquine-induced itch evoke diverse response patterns across the mouse brain. In summary, our study provides a comprehensive dataset for the diverse activity pattern of mouse brain during the itch-scratching cycle, paving the way for further exploration into the neural mechanisms underlying the itch-scratching cycle.

Predictors of dopamine dysregulation syndrome in patients with early Parkinson's disease.

BACKGROUND: Dopamine dysregulation syndrome (DDS) is a complication of Parkinson's disease (PD) that seriously affects the quality of life of PD patients. Currently, the risk factors for DDS are poorly known, and it is critical to identify them in the early stages of PD. OBJECTIVE: To explore the incidence of and risk factors for DDS in patients with early PD. METHODS: A retrospective cohort study was conducted on the general data, clinical features, and imaging data of patients with early PD in the PPMI database. Multivariate Cox regression analysis was performed to analyze the risk factors for the development of DDS in patients with early PD, and Kaplan‒Meier curves examined the frequency and predictors of incident DDS symptoms. RESULTS: At baseline, 2.2% (n = 6) of patients with early PD developed DDS, and the cumulative incidence rates of DDS during the 5-year follow-up period were 2.8%, 6.4%, 10.8%, 15.5%, and 18.7%, respectively. In the multivariate Cox regression model controlling for age, sex, and drug use, hypersexuality (HR = 3.088; 95% CI: 1.416~6.732; P = 0.005), compulsive eating (HR = 3.299; 95% CI: 1.665~6.534; P = 0.001), compulsive shopping (HR = 3.899; 95% CI: 1.769~8.593; P = 0.001), anxiety (HR = 4.018; 95% CI: 2.136~7.599; P < 0.01), and lower Hoehn-Yahr (H-Y) stage (HR = 0.278; 95% CI: 0.152~0.509; P < 0.01) were independent risk factors for DDS in patients with early PD. PD patients with DDS had lower DAT uptake values than those patients without DDS. CONCLUSION: Early PD patients with hypersexuality, compulsive eating, compulsive shopping, anxiety, and lower H-Y stage were at increased risk for DDS. The occurrence of DDS may be related to the decrease in the average DAT uptake of the caudate and putamen.

Alpha-synuclein in skin as a high-quality biomarker for Parkinson's disease.

Parkinson's disease (PD), the most common neurological motor system disorder, which characterised by the irreversible loss of dopaminergic neurones in the substantia nigra pars compacta, and leads to the deficiency of dopamine in the striatum. Deposited Lewy bodies (LBs) in diseased neurones and nerve terminals are the pathological hallmark of PD, and alpha-synuclein (α-Syn) is the most prominent protein in LBs. The tight association between α-Syn and the molecular pathology of PD has generatly increaed the interest in using the α-Syn species as biomarkers to diagnose early PD. α-Syn is not confined to the central nervous system, it is also present in the peripheral tissues, such as human skin. The assessment of skin α-Syn has the potential to be a diagnostic method that not only has excellent sensitivity, specificity, and reproducibility, but also convenient and acceptable to patients. In this review, we (i) integrate the biochemical, aggregation and structural features of α-Syn; (ii) map the distribution of the α-Syn species present in the brain, biological fluids, and peripheral tissues; and (iii) present a critical and comparative analysis of previous studies that have measured α-Syn in the skin. Finally, we provide an outlook on the future of skin biopsy as a diagnostic approach for PD, and highlight its potential implications for clinical trials, clinical decision-making, treatment strategies as well as the development of new therapies.

Correlation between serum IGF-1 and EGF levels and neuropsychiatric and cognitive in Parkinson's disease patients.

BACKGROUND: Insulin-like growth factor 1 (IGF-1) and epidermal growth factor (EGF) exert neuroprotective effects in Parkinson's disease (PD). To date, studies on the relationships between serum IGF-1 and EGF levels and nonmotor symptoms in PD patients have been rare. METHODS: A Siemens automatic chemical analyzer was used to determine serum IGF-1 levels, and enzyme-linked immunosorbent assay was used to detect serum EGF levels in 100 healthy controls and 100 PD patients, including those in the early (n = 49) and middle-late (n = 51) stage of the disease. Evaluation of motor symptoms and nonmotor symptoms in PD patients was assessed by the associated scales. RESULTS: Serum IGF-1 and EGF levels were higher in PD patients than in healthy controls, and serum IGF-1 and EGF levels were higher in early stage PD patients than in middle-late stage PD patients. Serum IGF-1 levels were significantly negatively correlated with anxiety, depression, and cognitive dysfunction; serum EGF levels were significantly negatively correlated with cognitive dysfunction. Combining IGF-1 and EGF in the diagnosis of PD was more valuable than using a single factor in the diagnosis. CONCLUSIONS: This study shows that serum IGF-1 levels were correlated with the nonmotor symptoms of anxiety, depression, and cognitive dysfunction and that EGF levels were correlated with cognitive dysfunction. The combination of IGF-1 and EGF increased the value for a PD diagnosis. This is the first report of the simultaneous detection of IGF-1 and EGF levels to explore the correlation with nonmotor symptoms of PD.

A Novel Prognostic Signature Associated With the Tumor Microenvironment in Kidney Renal Clear Cell Carcinoma.

Background: The tumor microenvironment (TME) is a complex and evolving environment, and the tumor immune microenvironment in kidney renal clear cell carcinoma (KIRC) has a strong suppressive profile. This study investigates the potential prognostic role and value of genes of the tumor microenvironment in KIRC. Methods: The transcriptome sequencing data of 530 cases and 39 cases of KIRC and the corresponding clinical prognosis information were downloaded from TCGA data and GEO data, respectively, and TME-related gene expression profiles were extracted. A prognostic signature was constructed and evaluated using univariate Cox regression analysis and LASSO regression analysis. Gene set enrichment analysis (GSEA) was used to obtain the biological process of gene enrichment in patients with high and low-risk groups. Results: A prognostic signature consisting of eight TME-related genes (LRFN1, CSF1, UCN, TUBB2B, SERPINF1, ADAM8, ABCB4, CCL22) was constructed. Kaplan-Meier survival analysis yielded significantly lower survival times for patients in the high-risk group than in the low-risk group, and the AUC values for the ROC curves of this prognostic signature were essentially greater than 0.7, and univariate and multifactorial Cox regression analyses indicated that the risk score was independent risk factors for KIRC prognosis. GSEA analysis showed that immune-related biological processes were enriched in the high-risk group and that risk values were strongly associated with multiple immune cell scores and immune checkpoint-related genes (PDCD1, CTLA4). Conclusions: The prognostic signature can accurately predict the prognosis of KIRC patients, which may provide new ideas for future precision immunotherapy of KIRC.

Insulin-like growth factor in Parkinson's disease is related to nonmotor symptoms and the volume of specific brain areas.

BACKGROUND: Insulin-like growth factor 1 (IGF-1) plays a protective role in Parkinson's disease (PD). To date, studies on the relationship between plasma IGF-1 levels and nonmotor symptoms and brain gray matter volume in PD patients have been rare. METHODS: A Siemens automatic chemical analyzer was used to determine plasma IGF-1 levels in 55 healthy controls and 119 PD patients, including those at the early (n = 67) and middle-late (n = 52) stages of the disease. Evaluation of motor symptoms and nonmotor symptoms in PD patients was assessed by the associated scales. Image acquisition in 65 PD patients was performed using a Siemens MAGNETOM Prisma 3 T magnetic resonance imaging (MRI) scanner. RESULTS: Plasma IGF-1 levels in early-stage PD patients were higher than those in healthy controls, and plasma IGF-1 levels in early-stage PD patients were higher than those in middle-late-stage PD patients. Plasma IGF-1 levels were significantly negatively correlated with anxiety, depression and cognitive dysfunction. Receiver operating characteristic (ROC) curve assessment confirmed that plasma IGF-1 levels had good predictive accuracy for PD with anxiety, depression and cognitive dysfunction. Furthermore, plasma IGF-1 levels were significantly positively correlated with volumes in the insula, caudate and anterior cingulate. CONCLUSIONS: This study shows that plasma IGF-1 levels were correlated with the nonmotor symptoms of anxiety, depression and cognitive dysfunction and the volume in specific brain areas. This is the first report examining the relationships between plasma IGF-1 and clinical manifestations and imaging features in PD patients.

Family Resilience and Adolescent Mental Health during COVID-19: A Moderated Mediation Model.

BACKGROUND: The COVID-19 pandemic has impacted and is still impacting people's lives, including physical and mental health. Family plays an important role in adolescent mental health due to the long staying at home. AIMS: This paper aimed to investigate the impact of family resilience on adolescent mental health during the COVID-19 pandemic, and the mediation role of pandemic stress perception and the moderation role of meta-mood. METHODS: A total of 2691 Chinese adolescents were recruited using convenient sampling. Their mental health, family resilience, pandemic stress perception and meta-mood were surveyed. Multivariate statistics were used to analyze the data. RESULTS: Our results showed that (1) about 36.7% adolescents in our sample have some mental health problems; (2) family resilience can positively predict adolescent mental health, whereas pandemic stress perception can negatively predict mental health; (3) pandemic stress perception mediates the relationship between family resilience and adolescent mental health; (4) meta-mood moderates the relationship between family resilience and pandemic perception, i.e., the first half of the mediation role. CONCLUSIONS: Our results indicate that one can either improve family resilience or improve adolescents' meta-mood to relieve adolescents' mental health problems.

Single-neuron projectome of mouse prefrontal cortex.

Prefrontal cortex (PFC) is the cognitive center that integrates and regulates global brain activity. However, the whole-brain organization of PFC axon projections remains poorly understood. Using single-neuron reconstruction of 6,357 mouse PFC projection neurons, we identified 64 projectome-defined subtypes. Each of four previously known major cortico-cortical subnetworks was targeted by a distinct group of PFC subtypes defined by their first-order axon collaterals. Further analysis unraveled topographic rules of soma distribution within PFC, first-order collateral branch point-dependent target selection and terminal arbor distribution-dependent target subdivision. Furthermore, we obtained a high-precision hierarchical map within PFC and three distinct functionally related PFC modules, each enriched with internal recurrent connectivity. Finally, we showed that each transcriptome subtype corresponds to multiple projectome subtypes found in different PFC subregions. Thus, whole-brain single-neuron projectome analysis reveals organization principles of axon projections within and outside PFC and provides the essential basis for elucidating neuronal connectivity underlying diverse PFC functions.

Plasma arylsulfatase A levels are associated with cognitive function in Parkinson's disease.

BACKGROUND: Arylsulfatase A (ARSA), a lysosomal enzyme, has been shown to inhibit the aggregation and propagation of α-synuclein (α-syn) through its molecular chaperone function. The relationship between ARSA levels and Parkinson's disease (PD) in the Chinese Han population remains controversial, and few quantitative research studies have investigated the relationship between plasma ARSA levels and PD. OBJECTIVES: The purpose of this study was to investigate the relationships between ARSA levels and cognitive function in PD patients and to evaluate the association of ARSA and α-syn levels with nonmotor symptoms. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma ARSA and α-syn levels in 50 healthy controls, 120 PD patients (61 PD patients with no cognitive impairment (PD-NCI) and 59 PD patients with cognitive impairment (PD-CI)). Motor symptoms and nonmotor symptoms (cognitive function, Unified Parkinson's Disease Rating Scale (UPDRS) score, depression, anxiety, constipation, olfactory dysfunction, sleep disruption, and other symptoms) were assessed with the relevant scales. The Kruskal-Wallis H test was used for comparison between groups, and Pearson/Spearman analysis was used for correlation analysis. RESULTS: The plasma ARSA concentrations were lower in the PD-CI group than in the PD-NCI group. The plasma α-syn levels in the PD-CI group were higher than those in the healthy control group, and the plasma ARSA levels were correlated with the Mini-Mental State Examination (MMSE scores) and Hoehn and Yahr (H-Y) stage. CONCLUSION: We used a quantitative assessment method to show that low plasma ARSA levels and high α-syn levels are related to cognitive impairment in PD patients. Plasma ARSA levels gradually decrease with PD progression.

Application of m6A and TME in Predicting the Prognosis and Treatment of Clear Cell Renal Cell Carcinoma.

Background: Previous studies have shown that RNA N6-methyladenosine (m6A) plays an important role in the construction of the tumor microenvironment (TME). However, how m6A plays a role in the TME of clear cell renal cell carcinoma remains unclear. Methods: Based on 23 m6A modulators, we applied consensus cluster analysis to explore the different m6A modification profiles of ccRCC. The CIBERSORT method was employed to reveal the correlation between TME immune cell infiltration and different m6A modification patterns. A m6A score was constructed using a principal component analysis algorithm to assess and quantify the m6A modification patterns of individual tumors. Results: Three distinct m6A modification patterns of ccRCC were identified. The characteristics of TME cell infiltration in these three patterns were consistent with immune rejection phenotype, immune inflammation phenotype, and immune desert phenotype. In particular, when m6A scores were high, TME was characterized by immune cell infiltration and patient survival was higher (p < 0.05). When m6A scores were low, TME was characterized by immunosuppression and patient survival was lower (p < 0.05). The immunotherapy cohort confirmed that patients with higher m6A scores had significant therapeutic advantages and clinical benefits. Conclusions: The m6A modification plays an important role in the formation of TME. The m6A scoring system allows the identification of m6A modification patterns in individual tumors, discriminates the immune infiltrative features of TME, and provides more effective prognostic indicators and treatment strategies for immunotherapy.

MicroRNA-181a-2-3p shuttled by mesenchymal stem cell-secreted extracellular vesicles inhibits oxidative stress in Parkinson's disease by inhibiting EGR1 and NOX4.

The current study investigated the physiological mechanisms by which extracellular vesicle (EV)-encapsulated miR-181a-2-3p derived from mesenchymal stem cells (MSCs) might mediate oxidative stress (OS) in Parkinson's disease (PD). First, 6-hydroxydopamine (6-OHDA)-induced PD cell and mouse models were established, after which miR-181a-2-3p, EGR1, and NOX4 expression patterns were determined in SH-SY5Y cells and substantia nigra (SN) of PD mice. Next, the binding affinity among miR-181a-2-3p, EGR1, and NOX4 was identified using multiple assays. Gain- or loss-of-function experiments were further adopted to detect SH-SY5Y cell proliferation and apoptosis and to measure the levels of SOD, MDA, and ROS. Finally, the effects of miR-181a-2-3p from MSC-derived EVs in PD mouse models were also explored. It was found that miR-181a-2-3p was poorly expressed in 6-OHDA-induced SH-SY5Y cells, whereas miR-181a-2-3p from MSCs could be transferred into SH-SY5Y cells via EVs. In addition, miR-181a-2-3p could target and inhibit EGR1, which promoted the expression of NOX4. The aforementioned miR-181a-2-3p shuttled by MSC-derived EVs facilitated SH-SY5Y proliferation and SOD levels, but suppressed apoptosis and MDA and ROS levels by regulating EGR1 via inhibition of NOX4/p38 MAPK, so as to repress OS of PD. Furthermore, in PD mice, miR-181a-2-3p was carried by EVs from MSCs to alleviate apoptosis of dopamine neurons and OS, accompanied by increased expressions of α-syn and decreased 4-HNE in SN tissues. Collectively, our findings revealed that MSC-derived EV-loaded miR-181a-2-3p downregulated EGR1 to inhibit OS via the NOX4/p38 MAPK axis in PD.

Association between Parent-Child Relationship and Second-Time Mother's Prenatal Depressive Symptoms: The Mediation Role of Parenting Burnout.

PURPOSE: The aim of this research was to study the association between the mother-firstborn relationship and second-time mothers' prenatal depressive symptoms before the birth of a second child and the mediation role of parenting burnout on this relationship. METHODS: Empirical study was adopted in this research. Using a convenient sampling method, we recruited 110 second-time mothers who were in their third trimester of pregnancy. Child-parent relationship questionnaire, parenting burnout scale, and Beck Depression Instrument were used to measure the relationship between firstborn and second-time mothers, mothers' parenting burnout, and prenatal depressive symptoms, respectively. Regression analysis was conducted to test the relationship between variables, and the mediation effect was tested using PROCESS. RESULTS: Regression results showed that the parent-child relationship is negatively associated with second-time mothers' prenatal depressive symptoms. The parent-child relationship is negatively associated with parenting burnout which is positively related to prenatal depressive symptoms. When considering the mediation variable of parenting burnout, the direct effect is not statistically significant. CONCLUSIONS: Parent-child relationship has a significant impact on second-time mothers' prenatal depressive symptoms, and this relationship is mediated by parenting burnout.