Plasma exosomes carrying mmu-miR-146a-5p and Notch signalling pathway-mediated synaptic activity in schizophrenia.

BACKGROUND: Schizophrenia is characterized by a complex interplay of genetic and environmental factors, leading to alterations in various molecular pathways that may contribute to its pathogenesis. Recent studies have shown that exosomal microRNAs could play essential roles in various brain disorders; thus, we sought to explore the potential molecular mechanisms through which microRNAs in plasma exosomes are involved in schizophrenia. METHODS: We obtained sequencing data sets (SUB12404730, SUB12422862, and SUB12421357) and transcriptome sequencing data sets (GSE111708, GSE108925, and GSE18981) from mouse models of schizophrenia using the Sequence Read Archive and the Gene Expression Omnibus databases, respectively. We performed differential expression analysis on mRNA to identify differentially expressed genes. We conducted Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to determine differentially expressed genes. Subsequently, we determined the intersection of differentially expressed microRNAs in plasma exosomes and in prefrontal cortex tissue. We retrieved downstream target genes of mmu-miR-146a-5p from TargetScan and used Cytoscape to visualize and map the microRNA-target gene regulatory network. We conducted in vivo experiments using MK-801-induced mouse schizophrenia models and in vitro experiments using cultured mouse neurons. The role of plasma exosomal miR-146a-5p in schizophrenia was validated using a cell counting kit, detection of lactate dehydrogenase, dual-luciferase assay, quantitative reverse transcription polymerase chain reaction, and Western blot analysis. RESULTS: Differential genes were mainly enriched in synaptic regulation-related functions and pathways and were associated with neuronal degeneration. We found that mmu-miR-146a-5p was highly expressed in both prefrontal cortical tissue and plasma exosomes, which may be transferred to lobe cortical vertebral neurons, leading to the synergistic dysregulation of gene network functions and, therefore, promoting schizophrenia development. We found that mmu-miR-146a-5p may inhibit the Notch signalling pathway-mediated synaptic activity of mouse pyramidal neurons in the lobe cortex by targeting NOTCH1, which in turn could promote the onset and development of schizophrenia in mice. LIMITATIONS: The study's findings are based on animal models and in vitro experiments, which may not fully replicate the complexity of human schizophrenia. CONCLUSION: Our findings suggest that mmu-miR-146a-5p in plasma-derived exosomes may play an important role in the pathogenesis of schizophrenia. Our results provide new insights into the underlying molecular mechanisms of the disease.

Identification of Immune-Related Gene Signature in Schizophrenia.

BACKGROUND: Schizophrenia (SCZ) is a type of psychiatric disorder characterized by multiple symptoms. Our aim is to decipher the relevant mechanisms of immune-related gene signatures in SCZ. METHODS: The SCZ dataset and its associated immunoregulatory genes were retrieved using Gene Expression Omnibus (GEO) and single-sample gene set enrichment analysis (ssGSEA). Co-expressed gene modules were determined through weighted gene correlation network analysis (WGCNA). To elucidate the functional characteristics of these clusters, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used. Additionally, gene set enrichment analysis (GSEA) and Gene Set Variation Analysis (GSVA) were conducted to identify enriched pathways for the immune subgroups. A protein-protein interaction (PPI) network analysis was performed to identify core genes relevant to SCZ. RESULTS: A significantly higher immune score was observed in SCZ compared to control samples. Seven distinct gene modules were identified, with genes highlighted in green selected for further analysis. Using the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) method, degrees of immune cell adhesion and accumulation related to 22 different immune cell types were calculated. Significantly enriched bioprocesses concerning the immunoregulatory genes with differential expressions included interferon-beta, IgG binding, and response to interferon-gamma, according to GO and KEGG analyses. Eleven hub genes related to immune infiltration emerged as key players among the three top-ranked GO terms. CONCLUSIONS: This study underscores the involvement of immunoregulatory reactions in SCZ development. Eleven immune-related genes (IFITM1 (interferon induced transmembrane protein 1), GBP1 (guanylate binding protein 1), BST2 (bone marrow stromal cell antigen 2), IFITM3 (interferon induced transmembrane protein 3), GBP2 (guanylate binding protein 2), CD44 (CD44 molecule), FCER1G (Fc epsilon receptor Ig), HLA-DRA (major histocompatibility complex, class II, DR alpha), FCGR2A (Fc gamma receptor IIa), IFI16 (interferon gamma inducible protein 16), and FCGR3B (Fc gamma receptor IIIb)) were identified as hub genes, representing potential biomarkers and therapeutic targets associated with the immune response in SCZ patients.

Health insurance status and its determinants among patients with type 2 diabetes mellitus in a tertiary teaching hospital in Malaysia.

INTRODUCTION: Even in a country with a tax-based healthcare financing system, health insurance can play an important role, especially in the management of chronic diseases with high disease and economic burden such as Type 2 Diabetes Mellitus (T2DM). The insurance coverage among T2DM patients in Malaysia is currently unclear. The aim of this study was to determine the insurance status of T2DM patients in public and private healthcare facilities in Malaysia, and the association between this status and patients' sociodemographic and economic factors. METHODS: A cross-sectional study among T2DM patients seeking inpatient or outpatient treatment at a public tertiary hospital (Hospital Canselor Tuanku Muhriz) and a private tertiary hospital (Universiti Kebangsaan Malaysia Specialist Centre) in Kuala Lumpur between August 2019 and March 2020. Patients were identified via convenience sampling using a self-administered questionnaire. Data collection focused on identifying insurance status as the dependent factor while the independent factors were the patients' sociodemographic characteristics and economic factors. RESULTS: Of 400 T2DM patients, 313 responded (response rate, 78.3%) and 76.0% were uninsured. About 69.6% of the respondents had low monthly incomes of

Recent perspectives and awareness on transmission, clinical manifestation, quarantine measures, prevention and treatment of COVID-19 among people living in Malaysia in 2020.

Background: There is a major public health challenge threatening the world with the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in December 2019 from Wuhan, China. Objective: The aim of this study was to assess the knowledge, attitude and practice regarding COVID-19 and its transmission, causes and prevention among people living in Malaysia. Methods: A cross-sectional study was conducted among people living in Malaysia by using an online survey in March and April 2020. Results: Out of 520 respondents, the mean age was 36.9 ± 14.9, between 19 and 67 years with the majority being female. Most respondents had good knowledge, attitude and practice towards COVID-19 with mean ± sd 18.2 ± 1.7, 5.2 ± 1.1 and 4.1 ± 1.4, respectively. In addition, the majority had good knowledge regarding cause, mode of transmission, signs and symptoms, prevention and treatment and quarantine measures after answering 21 questions. Conclusion: To date, there is no specific treatment or vaccine for COVID-19, thus staying at home is the best preventive measure to curb the further growth of positive cases in the country. These findings could provide an insight in designing effective preparedness for future pandemic outbreaks.

Maggot debridement therapy to treat hard-to-heal diabetic foot ulcers: a single-centre study.

OBJECTIVE: Maggot debridement therapy (MDT) has seen a resurgence in recent years in the treatment of hard-to-heal wounds, as a result of rising antibiotic resistance. The sterilised larvae of Lucilia cuprina have been used in MDT in Malaysia since 2003, with encouraging results for the treatment of hard-to-heal diabetic wounds. We report a case series of 30 patients selected from our clinic by convenient sampling with diabetic lower limb ulcers treated with MDT. The average age of patients receiving MDT was >50 years. Of the 30 patients in the study, nine were female and 21 were male. All patients had underlying diabetes, two patients had leg ulcers and 28 patients had diabetic foot ulcers. Sterilised Lucilia cuprina larvae were applied via a standard method of 10 maggots per square centimetre and dressed with sterile gauze. The study endpoint was defined as ≤5% coverage with slough or necrotic tissue following three successive applications of MDT. In this study, maximum debridement of wounds was achieved in 96.6% (29 patients) of our patients, with ≤5% coverage with slough or necrotic tissue, in addition to a reduction in wound-related pain, as assessed by a visual analogue scale. No adverse events were reported. The findings of this study support the use of MDT as a safe, efficacious, and cost-effective method of managing diabetic wounds.