Pharmacology
Navigating the Complex Landscape of Autism Spectrum Disorder: Challenges and Opportunities in Diagnosis, Treatment, and Supports
Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by persistent deficits in social communication and interaction as well as restricted repetitive patterns of behaviour interests or activities. Despite advancements in our understanding of ASD identification screening diagnosing and treating this condition present significant challenges. This review article comprehensively examines the current diagnostic and treatment landscape for ASD addressing key issues and opportunities for improvement. The diagnostic criteria for ASD as outlined in the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) provide a framework for identifying the condition. Still the heterogeneity of presentation and the presence of comorbidities contribute to diagnostic complexity. Early intervention is crucial for improving outcomes in individuals with ASD; however accessing timely and appropriate interventions can be challenging. A diverse range of interventions exists for individuals with ASD including behavioural therapies pharmacological treatments gene expression and alternative therapies. However the efficacy and accessibility of these treatments vary and navigating the treatment landscape can be daunting for caregivers and clinicians alike. Moreover due to the persistence of healthcare disparities underserved populations face barriers to diagnosis and treatment. Transitioning to adulthood poses unique challenges for individuals with ASD including finding employment and accessing support services. Additionally ASD affects not only individuals diagnosed with the condition but also their families and caregivers. Addressing caregiver stress and burnout is essential for providing holistic care to individuals with ASD and their families. This review also identifies areas needing further research such as personalized medicine and healthcare disparities and discusses policy implications for enhancing ASD care and support. By highlighting research needs and policy considerations this review aims to inform future efforts to improve ASD Screening diagnosis and treatment ultimately striving to enhance outcomes for individuals with ASD and their families.
TSIX: A Novel Long Noncoding RNA in Cancer Development and Progression
Long noncoding RNAs (LncRNAs) represent a group of long noncoding RNA molecules exceeding 200 nt in length and lacking the capacity for protein coding. In recent years the function and progress of lncRNA have attracted the attention of more and more researchers. Specifically the long non-coding RNA TSIX (TSIX transcript XIST antisense RNA) plays a significant role in ensuring random X-chromosome inactivation. Recent investigations have highlighted the involvement of lncRNA TSIX in the development of various cancers emphasizing its crucial functions in tumorigenesis. TSIX has emerged as a novel cancer-associated lncRNA and it is identified for its aberrant expression in diverse tumors such as those of the breast gastric hepatocellular head and neck lung esophageal squamous cell and uterine smooth muscle. Furthermore lncRNA TSIX regulates mRNA expression by binding to specific miRNAs utilizing a competitive endogenous RNA regulatory mechanism. This interaction significantly influences tumor cell proliferation migration invasion and apoptosis. LncRNA TSIX may serve as a useful biomarker or a prospective therapeutic target in a variety of malignant cancers because of the biological functions and mechanisms associated with it.
Stem Cell Nanotechnology Applications as Drug Delivery Systems for Cancer Therapy: A New Era in Targeted Treatment
Cancer is still one of the most serious and life-threatening diseases in humans and the conventional chemotherapies radiation treatments and surgical methods have yet to provide an effective resolution due to some drawbacks concerning drug resistance general toxicity and poor targeting to tumor sites. To surmount these challenges some innovative approaches are under exploration; hence the emergence of more promising solutions in the format of nanotechnology that combine with stem cell (SC)-based drug delivery systems (DDS). Its advantages include autonomous proliferative potential and the ability to clonally generate various cell types leading to malignant transformation. Additionally they possess an innate ability to migrate toward tumor sites making them highly effective vectors for targeted DDS. The integration of nanotechnology with SCs offers several benefits such as controlled release of therapeutic molecules improved bioavailability and reduced systemic toxicity. These advantages may provide the opportunity to improve cancer therapy with fewer side effects than those resulting from conventional treatments. This review has focused on the emerging role of SC-nanotechnology-based DDS as a new era in targeted cancer treatment and has emphasized enhancing therapeutic outcomes with a more precise approach to cancer therapy.
Neuroprotective Effects of Thymol-Loaded Selenium Nanoparticles against 6-OHDA-Induced Apoptosis and Oxidative Stress in an In Vitro Parkinson’s Disease Model
Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic neurons within the substantia nigra leading to progressive motor dysfunction. There are still limited disease-modifying options that counteract the process of disease progression. This study aimed to evaluate the neuroprotective effects of thymol both in its free form and when loaded onto selenium nanoparticles (SeNPs) in a 6-hydroxydopamine (6-OHDA)-induced PD model using SH-SY5Y cells.
SeNPs were synthesized using a chemical reduction method with ascorbic acid achieving a 68% entrapment efficiency for thymol. FTIR analysis suggested an interaction between thymol and selenium which was confirmed by EDX analysis. Nano-Se-thymol particles were observed to be spherical with a mean size of 135.7 nm and a negative surface charge.
Nano-Se-thymol exhibited low toxicity in normal fibroblast cells and demonstrated greater neuroprotective effects against 6-OHDA-induced cytotoxicity compared to thymol. Nano-Se-thymol significantly reduced ROS generation and increased cell viability compared to 6-OHDA. Furthermore Nano-Se-thymol decreased the expression of NF-κB inflammatory markers and caspase-3 apoptotic proteins which were elevated by 6-OHDA compared to thymol alone.
Nano-Se-Thymol significantly attenuates 6-OHDA-induced cytotoxicity in an established in vitro model of PD. The neuroprotective efficacy of Nano-Se-Thymol is attributed to its enhanced antioxidant capacity as evidenced by a significant reduction in ROS levels along with its ability to inhibit apoptosis and modulate cell cycle progression.
Nano-Se-thymol is a potential disease-modifying agent for the treatment of PD; however further studies and long-term safety assessments are essential to confirm these benefits and understand the underlying mechanisms.
Single-Cell Transcriptome and Microbiome Profiling Uncover Ileal Immune Impairment in Intrauterine Growth-Retarded Piglets
Impaired intestinal immune function is commonly observed in neonates with intrauterine growth retardation (IUGR) yet its underlying mechanisms and regulatory pathways remain poorly understood. Therefore we aimed to investigate gene regulatory patterns and microbiota alterations in IUGR piglets.
Three newborn IUGR piglets and three normal littermates were selected from the same sow and sacrificed at seven days of age. Ileal digesta was collected for 16S rRNA amplicon sequencing (16S-seq) and ileum segments were dissociated for single-cell RNA sequencing (scRNA-seq).
The scRNA-seq results revealed a reduced proportion of plasma B cells in IUGR piglets along with alterations in the distribution of various T cell subsets. KEGG pathway analysis further indicated a downregulation of the B cell receptor signaling pathway in B cells from IUGR piglets. In contrast both the T cell receptor signaling pathway and antigen processing and presentation were attenuated in T cells. Pseudotime trajectory analysis suggested that the differentiation of B cells was impaired in IUGR piglets. SCENIC analysis revealed that GATA3 IRF2 and BCL11A were downregulated in T cells of IUGR piglets. The 16S-seq results revealed that α-diversity was lower in IUGR piglets. At the genus level the relative abundance of Prevotella was significantly lower in IUGR piglets.
Significant changes were identified in the proportions of B and T cells their associated signaling pathways and intestinal microbiota composition in IUGR piglets suggesting underlying immune dysfunction and dysbiosis.
We identified novel immune-related transcription factors and key microbes as potential therapeutic targets shedding light on strategies for preventing and treating IUGR.
Mebendazole as an Adjunct Therapy with Mesalamine to Increase Efficacy and Maintenance Therapy for Ulcerative Colitis Patients: A Pilot Study
Ulcerative colitis (UC) is an inflammatory disorder of the large intestine characterized by inflammation in the mucosal tissue of the colon and rectal area. In the present pilot study we assessed the efficacy of combining mebendazole with mesalamine in moderate UC patients.
In the present exploratory pilot trial designed to assess both the safety and preliminary efficacy of mebendazole a total number of 10 moderate UC patients with Mayo scores ranging from 6 to 9 were enrolled. The participants were divided into two groups at random and were treated with 3 gr mesalamine per day plus 300 mg/day mebendazole or matching placebo for 3 months. The efficacy of treatment was assessed in 8 and 12-week timelines with Mayo score. Moreover the safety of the given dose of mebendazole in UC patients was also assessed by laboratory tests.
The addition of mebendazole to the mesalamine in the treatment regimen of patients suffering from UC caused a greater decrease in the Mayo score of the patients compared to the mesalamine monotherapy at 8 and 12-week timelines. Despite this trend statistical significance was not reached likely due to the limited sample size. Moreover all the patients in the mebendazole group experienced clinical remission at the 12-week timeline but 4 of 5 patients in the placebo group experienced a clinical remission state indicating that mebendazole caused a 20% increase in the clinical remission rate. As indicated by the results of the laboratory tests the given dose of mebendazole showed no toxicity in the patients.
The addition of mebendazole to mesalamine for UC treatment appears to be a safe and potentially beneficial approach to enhance mesalamine’s efficacy and reduce clinical symptoms. However given the small sample size and the short study duration further large-scale long-term trials are necessary to validate these preliminary findings.
IRCT20220115053713N2.