Metformin: A Dual-Role Player in Cancer Treatment and Prevention.

Cancer continues to pose a significant global health challenge, as evidenced by the increasing incidence rates and high mortality rates, despite the advancements made in chemotherapy. The emergence of chemoresistance further complicates the effectiveness of treatment. However, there is growing interest in the potential of metformin, a commonly prescribed drug for type 2 diabetes mellitus (T2DM), as an adjuvant chemotherapy agent in cancer treatment. Although the precise mechanism of action of metformin in cancer therapy is not fully understood, it has been found to have pleiotropic effects, including the modulation of metabolic pathways, reduction in inflammation, and the regulation of cellular proliferation. This comprehensive review examines the anticancer properties of metformin, drawing insights from various studies conducted in vitro and in vivo, as well as from clinical trials and observational research. This review discusses the mechanisms of action involving both insulin-dependent and independent pathways, shedding light on the potential of metformin as a therapeutic agent for different types of cancer. Despite promising findings, there are challenges that need to be addressed, such as conflicting outcomes in clinical trials, considerations regarding dosing, and the development of resistance. These challenges highlight the importance of further research to fully harness the therapeutic potential of metformin in cancer treatment. The aims of this review are to provide a contemporary understanding of the role of metformin in cancer therapy and identify areas for future exploration in the pursuit of effective anticancer strategies.

Novel TLR7 hemizygous variant in post-COVID-19 neurological deterioration: a case report with literature review.

The neurological complications of coronavirus disease 2019 (COVID-19) can range from simple tremors and dystonia to features of encephalopathy. Toll-like receptor 7 (TLR7) belongs to a family of innate immune receptors responsible for viral RNA detection (such as SARS-CoV-2) and immune response initiation. TLR7 loss of function variants have been previously reported as genetic risk factors for severe COVID-19 infection in young patients with no comorbidities. In this case, we report a pediatric patient who developed severe long-term neurological deterioration following his COVID-19 infection. Presenting first to the clinic with episodic dystonia and finger spasticity, the patient's condition rapidly deteriorated with a significant drop in the Glasgow Coma Scale (GCS). Despite improvement following initial treatment with rituximab and intravenous immunoglobulin, the patient's symptoms relapsed, and GCS further dropped to 3/15. Serial brain magnetic resonance imaging scans revealed diffuse parenchymal atrophy, ventricular enlargement, and spinal cord thickening. Autoimmune investigations were negative but clinical whole genome sequencing prioritized four gene variants, the most significant of which was a novel frameshift null variant of the X chromosomal TLR7 gene (c.1386_1389dup, p.[His464Ilefs*7]). This case illustrates a role for TLR7 in long-term COVID-19 complications and highlights that TLR7 deficiency in the future may be addressed as a therapeutic measure.

Cerebrospinal fluid microRNAs as potential biomarkers in Alzheimer's disease.

Alzheimer's disease (AD) is the leading form of dementia worldwide, but its early detection and diagnosis remain a challenge. MicroRNAs (miRNAs) are a group of small endogenous RNA molecules that regulate mRNA expression. Recent evidence suggests miRNAs play an important role in the five major hallmarks of AD pathophysiology: amyloidogenesis, tauopathy, neuroinflammation, synaptic dysfunction, and neuronal death. Compared to traditional biomarkers of AD, miRNAs display a greater degree of stability in cerebrospinal fluid. Moreover, aberrant changes in miRNA expression can be measured over time to monitor and guide patient treatment. Specific miRNA profiles and combinations may also be used to distinguish AD subjects from normal controls and other causes of dementia. Because of these properties, miRNAs are now being considered as promising and potential biomarkers of AD. This review comprehensively summarizes the diagnostic potential and regulatory roles miRNAs play in AD.

Neutrophil extracellular traps in central nervous system pathologies: A mini review.

Neutrophils are the first cells to be recruited to sites of acute inflammation and contribute to host defense through phagocytosis, degranulation and neutrophil extracellular traps (NETs). Neutrophils are rarely found in the brain because of the highly selective blood-brain barrier (BBB). However, several diseases disrupt the BBB and cause neuroinflammation. In this regard, neutrophils and NETs have been visualized in the brain after various insults, including traumatic (traumatic brain injury and spinal cord injury), infectious (bacterial meningitis), vascular (ischemic stroke), autoimmune (systemic lupus erythematosus), neurodegenerative (multiple sclerosis and Alzheimer's disease), and neoplastic (glioma) causes. Significantly, preventing neutrophil trafficking into the central nervous system or NET production in these diseases alleviates brain pathology and improves neurocognitive outcomes. This review summarizes the major studies on the contribution of NETs to central nervous system (CNS) disorders.