Genetic and Regulatory Mechanisms of Comorbidity of Anxiety, Depression and ADHD: A GWAS Meta-Meta-Analysis Through the Lens of a System Biological and Pharmacogenomic Perspective in 18.5 M SubjectsLewandrowski, Blum, Sharafshah
et alJ Pers Med (2025) 15 (3)
Abstract: Background: In the United States, approximately 1 in 5 children experience comorbidities with mental illness, including depression and anxiety, which lead to poor general health outcomes. Adolescents with substance use disorders exhibit high rates of co-occurring mental illness, with over 60% meeting diagnostic criteria for another psychiatric condition in community-based treatment programs. Comorbidities are influenced by both genetic (DNA antecedents) and environmental (epigenetic) factors. Given the significant impact of psychiatric comorbidities on individuals' lives, this study aims to uncover common mechanisms through a Genome-Wide Association Study (GWAS) meta-meta-analysis. Methods: GWAS datasets were obtained for each comorbid phenotype, followed by a GWAS meta-meta-analysis using a significance threshold of p < 5E-8 to validate the rationale behind combining all GWAS phenotypes. The combined and refined dataset was subjected to bioinformatic analyses, including Protein-Protein Interactions and Systems Biology. Pharmacogenomics (PGx) annotations for all potential genes with at least one PGx were tested, and the genes identified were combined with the Genetic Addiction Risk Severity (GARS) test, which included 10 genes and eleven Single Nucleotide Polymorphisms (SNPs). The STRING-MODEL was employed to discover novel networks and Protein-Drug interactions. Results: Autism Spectrum Disorder (ASD) was identified as the top manifestation derived from the known comorbid interaction of anxiety, depression, and attention deficit hyperactivity disorder (ADHD). The STRING-MODEL and Protein-Drug interaction analysis revealed a novel network associated with these psychiatric comorbidities. The findings suggest that these interactions are linked to the need to induce "dopamine homeostasis" as a therapeutic outcome. Conclusions: This study provides a reliable genetic and epigenetic map that could assist healthcare professionals in the therapeutic care of patients presenting with multiple psychiatric manifestations, including anxiety, depression, and ADHD. The results highlight the importance of targeting dopamine homeostasis in managing ASD linked to these comorbidities. These insights may guide future pharmacogenomic interventions to improve clinical outcomes in affected individuals.
Hybridization Chain Reaction-Enhanced Ultrasensitive Electrochemical Analysis of miRNAs with a Silver Nano-Reporter on a Gold Nanostructured Electrode ArrayWang, Ma, Zhou
et alJ Funct Biomater (2025) 16 (3)
Abstract: Abnormal expression of miRNAs is associated with the occurrence and progression of cancer and other diseases, making miRNAs essential biomarkers for disease diagnosis and prognosis. However, the intrinsic properties of miRNAs, such as short length, low abundance, and high sequence homology, represent great challenges for fast and accurate miRNA detection in clinics. Herein, we developed a novel hybridization chain reaction (HCR)-based electrochemical miRNAs chip (e-miRchip), featured with gold nanostructured electrodes (GNEs) and silver nanoparticle reporters (AgNRs), for sensitive and multiplexed miRNA detection. AgNRs were synthesized and applied on the e-miRchip to generate strong redox signals in the presence of miRNA. The stem-loop capture probe was covalently immobilized on the GNEs, and was opened upon miRNA hybridization to consequently trigger the HCR for signal amplification. The multiple long-repeated DNA helix generated by HCR provides the binding sites for the AgNRs, contributing to the amplification of the electrochemical signals of miRNA hybridization. To optimize the detection sensitivity, GNEs with three distinct structures were electroplated, in which flower-like GNEs were found to be the best electrode morphology for miRNAs analysis. Under optimal conditions, the HCR-based e-miRchip showed an excellent detection performance with an LOD of 0.9 fM and a linear detection range from 1 fM to 10 pM. Moreover, this HCR-based e-miRchip platform was able to effectively distinguish miRNAs from the one- or two-base mismatches. This HCR-based e-miRchip holds great potential as a highly efficient and promising miRNA detection platform for the diagnosis and prognosis of cancer and other diseases in the future.
Comparison of the Properties of Acellular Matrix from the Skins of Cod (Gadus morhua) and Tilapia (Oreochromis mossambicus)Liu, Wei, Duan
et alJ Funct Biomater (2025) 16 (3)
Abstract: Acellular tissue matrices of fish skin origin are highly promising materials for tissue engineering due to their low biological risks and few religious restrictions. The main component of acellular fish skin matrices (AFSMs) is collagen, but collagen properties significantly differ between marine and freshwater fish. Although the characteristics of acellular matrices may vary, relevant reports about them are few. In this study, we used cod and tilapia fish skin as raw materials to prepare acellular matrices with low DNA content (≤50 ng/mg) and low endotoxin. They were denoted as C-AFSM (cod) and T-AFSM (tilapia) and had endotoxin removal rates of 92.47% and 96.73%, respectively. Their physicochemical properties, cytotoxicity, and wound healing effects were evaluated and compared. Scanning electron microscopy images showed that C-AFSM and T-AFSM had collagenous meshwork and high porosity. They also did not induce skin irritations. Their proliferation rates on mouse fibroblasts at 36 h were 192.21% ± 33.25% and 162.89% ± 36.47%, respectively. The wound healing effect of C-AFSM was faster than that of T-AFSM group (7 and 14 days: 45.3% ± 5.99% and 93.77% ± 1.58% for C-AFSM and 39.7% ± 2.84% and 93.35% ± 1.1% for T-AFSM, respectively). Therefore, the two acellular fish skin matrices can be used as tissue-engineering materials for wound repair, with C-AFSM being more effective than T-AFSM.
Optimization of Protoplast Preparation and Establishment of PEG-Mediated Genetic Transformation Method in Cordyceps cicadaeQi, Ruan, Wu
et alJ Fungi (Basel) (2025) 11 (3)
Abstract: Cordyceps cicadae (C. cicadae) is an important edible medicinal fungus; however, owing to its wild growth and lack of genome annotation, construction of a stable genetic transformation system in C. cicadae is greatly limited, impeding the extensive exploitation of C. cicadae in industry. Here, we successfully established an efficient plasmid transformation method within protoplasts of C. cicadae by PEG mediation using pCas9-EGFP as a marker plasmid. In order to overcome low transformation efficiency and acquire sufficient protoplasts for transformation, the influence of enzyme species, enzymatic hydrolysis time, enzymatic hydrolysis temperature, and fungal age on protoplast preparation were analyzed sequentially, and the optimal conditions for protoplast preparation were determined as follows: 2-day-old C. cicadae mycelia with 1.5% lywallzyme hydrolysis at 34 °C for 5 h. Our results indicate that no less than 5.1 × 107 CFU/mL protoplasts could be acquired. Additionally, five osmotic pressure stabilizers including potassium chloride (KCl), sodium chloride (NaCl), glucose, mannitol, and sucrose were employed to enhance the regeneration of protoplasts, among which sucrose exhibited the highest regeneration rate of 10.43%. The transformation efficiency of plasmid was 37.3 CFU/µg DNA. On this basis, a genetic transformation method was successfully constructed, laying the foundation for further gene editing and metabolic engineering of C. cicadae.
膜杰作
Star Staining
