The advent of RNA-based therapeutics for metabolic syndrome and associated conditions: a comprehensive review of the literature.

Metabolic syndrome (MetS) is a prevalent and intricate health condition affecting a significant global population, characterized by a cluster of metabolic and hormonal disorders disrupting lipid and glucose metabolism pathways. Clinical manifestations encompass obesity, dyslipidemia, insulin resistance, and hypertension, contributing to heightened risks of diabetes and cardiovascular diseases. Existing medications often fall short in addressing the syndrome's multifaceted nature, leading to suboptimal treatment outcomes and potential long-term health risks. This scenario underscores the pressing need for innovative therapeutic approaches in MetS management. RNA-based treatments, employing small interfering RNAs (siRNAs), microRNAs (miRNAs), and antisense oligonucleotides (ASOs), emerge as promising strategies to target underlying biological abnormalities. However, a summary of research available on the role of RNA-based therapeutics in MetS and related co-morbidities is limited. Murine models and human studies have been separately interrogated to determine whether there have been recent advancements in RNA-based therapeutics to offer a comprehensive understanding of treatment available for MetS. In a narrative fashion, we searched for relevant articles pertaining to MetS co-morbidities such as cardiovascular disease, fatty liver disease, dementia, colorectal cancer, and endocrine abnormalities. We emphasize the urgency of exploring novel therapeutic avenues to address the intricate pathophysiology of MetS and underscore the potential of RNA-based treatments, coupled with advanced delivery systems, as a transformative approach for achieving more comprehensive and efficacious outcomes in MetS patients.

Advancements and progress in juvenile idiopathic arthritis: A Review of pathophysiology and treatment.

Juvenile idiopathic arthritis (JIA) is a chronic clinical condition characterized by arthritic features in children under the age of 16, with at least 6 weeks of active symptoms. The etiology of JIA remains unknown, and it is associated with prolonged synovial inflammation and structural joint damage influenced by environmental and genetic factors. This review aims to enhance the understanding of JIA by comprehensively analyzing relevant literature. The focus lies on current diagnostic and therapeutic approaches and investigations into the pathoaetiologies using diverse research modalities, including in vivo animal models and large-scale genome-wide studies. We aim to elucidate the multifactorial nature of JIA with a strong focus towards genetic predilection, while proposing potential strategies to improve therapeutic outcomes and enhance diagnostic risk stratification in light of recent advancements. This review underscores the need for further research due to the idiopathic nature of JIA, its heterogeneous phenotype, and the challenges associated with biomarkers and diagnostic criteria. Ultimately, this contribution seeks to advance the knowledge and promote effective management strategies in JIA.

The paradoxical role of cytokines and chemokines at the tumor microenvironment: a comprehensive review.

Tumor progression and eradication have long piqued the scientific community's interest. Recent discoveries about the role of chemokines and cytokines in these processes have fueled renewed interest in related research. These roles are frequently viewed as contentious due to their ability to both suppress and promote cancer progression. As a result, this review critically appraised existing literature to discuss the unique roles of cytokines and chemokines in the tumor microenvironment, as well as the existing challenges and future opportunities for exploiting these roles to develop novel and targeted treatments. While these modulatory molecules play an important role in tumor suppression via enhanced cancer-cell identification by cytotoxic effector cells and directly recruiting immunological effector cells and stromal cells in the TME, we observed that they also promote tumor proliferation. Many cytokines, including GM-CSF, IL-7, IL-12, IL-15, IL-18, and IL-21, have entered clinical trials for people with advanced cancer, while the FDA has approved interferon-alpha and IL-2. Nonetheless, low efficacy and dose-limiting toxicity limit these agents' full potential. Conversely, Chemokines have tremendous potential for increasing cancer immune-cell penetration of the tumor microenvironment and promoting beneficial immunological interactions. When chemokines are combined with cytokines, they activate lymphocytes, producing IL-2, CD80, and IL-12, all of which have a strong anticancer effect. This phenomenon opens the door to the development of effective anticancer combination therapies, such as therapies that can reverse cancer escape, and chemotaxis of immunosuppressive cells like Tregs, MDSCs, and TAMs.

The clinical aspects of septo-optic dysplasia: A narrative review with illustrative case report.

INTRODUCTION AND IMPORTANCE: Septo-optic dysplasia (SOD) is a rare congenital disorder characterized by abnormal development of the optic nerve, pituitary gland, hypothalamus, and midline brain structures, with heterogeneous presentation among cases. CASE PRESENTATION: We report a seven-month-old male infant presented with persistent vomiting and delayed developmental milestones. He had dysmorphic facial features, bilateral esotropia, a head circumference of 50 cm, and scoliosis. His muscle tone was high (clasp-knife spasticity) and his deep tendon reflexes were brisk in the four limbs. Clinical evaluation and brain MRI confirmed the diagnosis of SOD, for which, he was subjected for multidisciplinary evaluation. Genetic testing revealed an autosomal dominant TUBB gene mutation. On follow-up, at the age of three years, he presented with recurrent focal motor and generalized seizures, which were controlled with levetiracetam. CLINICAL DISCUSSION: The ophthalmic manifestations of SOD include optic nerve hypoplasia, which can lead to visual impairments such as nystagmus, strabismus, and reduced visual acuity. Midline brain anomalies involve structures like the corpus callosum and septum pellucidum, and can result in cognitive and neurological deficits. Hypothalamic-pituitary axis abnormalities can cause endocrine dysfunction and growth abnormalities. The clinical heterogeneity of SOD is attributed to variable phenotypic penetration and genetic mutations. Environmental risk factors may also contribute to the development of the syndrome. CONCLUSION: SOD is a complex disorder with diverse clinical manifestations. Early diagnosis and multidisciplinary management are crucial for optimizing patient outcomes. Further research is needed to understand the underlying genetic and environmental factors involved in SOD and to develop targeted treatments.

Barriers and shortcomings in access to cardiovascular management and prevention for familial hypercholesterolemia during the COVID-19 pandemic.

Familial hypercholesterolemia (FH) is a hereditary condition caused by mutations in the lipid pathway. The goal in managing FH is to reduce circulating low-density lipoprotein cholesterol and, therefore, reduce the risk of developing atherosclerotic cardiovascular disease (ASCVD). Because FH patients were considered high risk groups due to an increased susceptible for contracting COVID-19 infection, we hypothesized whether the effects of the pandemic hindered access to cardiovascular care. In this review, we conducted a literature search in databases Pubmed/Medline and ScienceDirect. We included a comprehensive analysis of findings from articles in English related and summarized the effects of the pandemic on cardiovascular care through direct and indirect effects. During the COVID-19 pandemic, FH patients presented with worse outcomes and prognosis, especially those that have suffered from early ASCVD. This caused avoidance in seeking care due to fear of transmission. The pandemic severely impacted consultations with lipidologists and cardiologists, causing a decline in lipid profile evaluations. Low socioeconomic communities and ethnic minorities were hit the hardest with job displacements and lacked healthcare coverage respectively, leading to treatment nonadherence. Lock-down restrictions promoted sedentary lifestyles and intake of fatty meals, but it is unclear whether these factors attenuated cardiovascular risk in FH. To prevent early atherogenesis in FH patients, universal screening programs, telemedicine, and lifestyle interventions are important recommendations that could improve outcomes in FH patients. However, the need to research in depth on the disproportionate impact within different subgroups should be the forefront of FH research.

COVID-19 Vaccine Booster Dose Acceptance: Systematic Review and Meta-Analysis.

The World Health Organization (WHO) recommended coronavirus disease 2019 (COVID-19) booster dose vaccination after completing the primary vaccination series for individuals ≥18 years and most-at-risk populations. This study aimed to estimate the pooled proportion of COVID-19 vaccine booster dose uptake and intention to get the booster dose among general populations and healthcare workers (HCWs). We searched PsycINFO, Scopus, EBSCO, MEDLINE Central/PubMed, ProQuest, SciELO, SAGE, Web of Science, Google Scholar, and ScienceDirect according to PRISMA guidelines. From a total of 1079 screened records, 50 studies were extracted. Meta-analysis was conducted using 48 high-quality studies according to the Newcastle-Ottawa Scale quality assessment tool. Using the 48 included studies, the pooled proportion of COVID-19 vaccine booster dose acceptance among 198,831 subjects was 81% (95% confidence interval (CI): 75-85%, I2 = 100%). The actual uptake of the booster dose in eight studies involving 12,995 subjects was 31% (95% CI: 19-46%, I2 = 100%), while the intention to have the booster dose of the vaccine was 79% (95% CI: 72-85%, I2 = 100%). The acceptance of the booster dose of COVID-19 vaccines among HCWs was 66% (95% CI: 58-74%), I2 = 99%). Meta-regression revealed that previous COVID-19 infection was associated with a lower intention to have the booster dose. Conversely, previous COVID-19 infection was associated with a significantly higher level of booster dose actual uptake. The pooled booster dose acceptance in the WHO region of the Americas, which did not include any actual vaccination, was 77% (95% CI: 66-85%, I2 = 100%). The pooled acceptance of the booster dose in the Western Pacific was 89% (95% CI: 84-92%, I2 = 100), followed by the European region: 86% (95% CI: 81-90%, I2 = 99%), the Eastern Mediterranean region: 59% (95% CI: 46-71%, I2 = 99%), and the Southeast Asian region: 52% (95% CI: 43-61%, I2 = 95). Having chronic disease and trust in the vaccine effectiveness were the significant predictors of booster dose COVID-19 vaccine acceptance. The global acceptance rate of COVID-19 booster vaccine is high, but the rates vary by region. To achieve herd immunity for the disease, a high level of vaccination acceptance is required. Intensive vaccination campaigns and programs are still needed around the world to raise public awareness regarding the importance of accepting COVID-19 vaccines needed for proper control of the pandemic.