Metformin, a widely prescribed biguanide for type 2 diabetes, has emerged as a promising candidate in skin cancer therapy due to its diverse anticancer mechanisms. Beyond its glucoselowering effects, metformin inhibits key oncogenic pathways, including the PI3K/AKT/mTOR and insulin/IGF-1 signaling pathways, activates AMP-activated protein kinase, and disrupts mitochondrial complex I function. These mechanisms are presumed to contribute to metformin's antiproliferative, pro-apoptotic, and anti-inflammatory effects, potentially reducing tumor growth and metastasis in melanoma and non-melanoma skin cancers. Predictive molecular docking studies reveal that metformin interacts with critical proteins in melanoma pathophysiology. Against PI3K/mTOR (PDB: 5OQ4), PTPN2 (PDB: 7UAD), and TRIP13 (PDB: 5VQA), metformin exhibited docking scores of -4.4, -4.6, and -5.6 kcal/mol, respectively, interacting via hydrogen bonding with residues such as ASP-836, ASP-964 (5OQ4), ASP-50 (7UAD), and SER-187, SER-138 (5VQA). Compared to standard inhibitors, PQR309 (-9.4 kcal/mol), ABBV-CLS-484 (-7.5 kcal/mol), and ATP (-10.8 kcal/mol), metformin displayed moderate binding affinity, suggesting potential but weaker inhibition of these targets. Preclinical and clinical studies support metformin's potential to reduce skin cancer risk, particularly in diabetic patients. However, challenges regarding bioavailability, optimal dosing, and patient selection persist, necessitating further investigation. Therefore, given its affordability, safety, and multitargeted action, metformin represents an attractive candidate for repurposing in skin cancer pharmacotherapy. Focusing future research on optimizing its therapeutic application, refining drug combinations, and identifying biomarkers would enhance clinical outcomes.
Background: Although statins are considered safe, they do have side effects with a wide range of hepatic adverse effects. The present study aims to estimate the frequency of liver injury in patients treated with various statins and to describe their clinical characteristics and outcomes. Materials and Methods: We carried out a secondary post hoc analysis of collected data from our previous study entitled “Frequency of Rhabdomyolysis in Patients Treated with Statins in Hamad General Hospital, Qatar.” Results: We identified 10 cases (1.0%) of statin-induced liver injury during the study period. Their mean age was 62±10.09 years, with 6 (60%) males and 4 (40%) females. Of the 10 patients, six patients received rosuvastatin, two patients received atorvastatin, and other two cases received simvastatin. The mean duration between the initiation of statin and the development of liver injury (latency period) was 20.40±6.91 months. Five of our patients were asymptomatic, and liver injury was discovered incidentally during routine testing of the patients during routine follow-up, while four patients developed painless jaundice and one developed muscle pain attributed to rhabdomyolysis. Statins were stopped in all patients. Nine of them were managed on an outpatient basis, while one patient with rhabdomyolysis was admitted. In all patients, other statins were reintroduced after a mean time of 7.4±3 months without recurrence of liver injury. No mortality has been reported. Conclusion: Our study demonstrated that statin-induced liver injury is a rare clinical entity that occurs regardless of the dose and type of statin, with rosuvastatin being the most causative drug. Statin-induced liver injury was asymptomatic and was discovered incidentally in 50% of our cases during routine testing, underscoring the importance of routine follow-up of liver function tests in asymptomatic patients.
The leaves of khat (Catha edulis) are chewed as a social habit for the central stimulant action of their cathinone content. There is growing concern about the health hazards of chronic khat chewing. Many authors have addressed the adverse effects of khat chewing on the cardiovascular and other systems. Based on a limited number of case reports and few prospective controlled studies, associations between khat chewing and the occurrence of myocardial infarction, dilated cardiomyopathy, and vascular diseases such as hypertension and cerebrovascular ischemia have been proposed. This review outlines the current knowledge on the adverse health effects of khat chewing on the cardiovascular system, assesses the strength and the limitations of the studies, and identifies the questions that the future studies should address.
We reported a case of cyclophosphamide (CYP)-induced posterior reversible encephalopathy syndrome (PRES) in a 26-year-old previously healthy male patient who was presented to the emergency department with a history of fever, shortness of breath, and hemoptysis. After extensive investigations, including bronchoscopy and autoimmune screening, he was diagnosed with renalpulmonary syndrome. The diagnosis of CYP-related PRES was based on the development of neurological clinical picture supported by magnetic resonance imaging findings. The dose of CYP was decreased to 75 mg/day, and the patient’s symptoms improved after 3 days.