The Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU) is a public university in Islamabad, Pakistan. Established on 21 March 2013, it offers undergraduate and postgraduate courses of medicine, surgery, dentistry, basic medical sciences and allied health professions..
Fluoride is a naturally occurring compound widely present in soil, water, rocks and is essential to maintain the physiological function and structure of bones and teeth. However, chronic exposure to elevated fluoride levels has been linked to adverse neurological effects. Despite its widespread environmental presence, the molecular mechanisms underlying fluoride-induced neurotoxicity remain incompletely understood. This study aimed to elucidate the effects of fluoride on oxidative stress, endoplasmic reticulum (ER) stress, apoptosis, and associated histopathological alterations in brain tissue. Forty Sprague–Dawley rats were randomly assigned to four groups (n = 10 per group; 5 male + 5 female) and administered sodium fluoride (NaF) in drinking water at concentrations of < 0.5 ppm (control), 50 ppm, 150 ppm, and 300 ppm for 90 consecutive days. The expression of antioxidant genes (SOD1 and GCLC), ER stress, and apoptosis-related genes (XBP1, GRP78, BCL-2, and BAX) was quantified using real-time quantitative PCR (RT-qPCR), and histopathological analysis of the brain tissues was performed. Fluoride exposure caused a dose-dependent downregulation of antioxidant and ER stress–related genes and concurrent upregulation of the pro-apoptotic genes. Histopathological analysis revealed structural damage in hippocampus and cerebral cortex, including neuronal shrinkage, vacuolization, and apoptotic features. These findings indicate that prolonged NaF exposure impairs antioxidant defenses, induces ER stress, and activates apoptotic pathways, thereby contributing to neuronal damage. This study provides mechanistic insights into fluoride-induced neurotoxicity and highlights the need for further research on potential therapeutic strategies targeting oxidative and ER stress pathways.
Porphyria cutanea tarda (PCT), caused by hepatic uroporphyrinogen decarboxylase deficiency, may rarely overlap with undiagnosed celiac disease (CD), complicating diagnosis due to shared hepatic and dermatologic features. Both conditions present with skin manifestations such as photosensitivity, blistering, or dermatitis herpetiformis-like lesions, often leading to misclassification. AI-driven metabolomics provides a novel strategy to identify metabolic biomarkers, predict CD with high accuracy through machine learning, and uncover hidden comorbidities in PCT patients. Despite challenges including limited datasets, bioinformatics demands, and regulatory barriers, integrating metabolomics with AI could enhance diagnostic precision and enable personalized management. Multidisciplinary collaboration is critical to translating these technologies into clinical practice for early detection and improved outcomes in PCT-CD overlap.
The shared risk factor approach (SRFA) provides a comprehensive framework that can effectively manage the growing global burden of oral and systemic diseases using a common modifiable risk factors approach. Oral health and major non-communicable diseases are closely linked risk factors such as tobacco use, unhealthy dietary patterns, physical inactivity, obesity, and inadequate oral hygiene. This chapter explores the relationship between dental health and the major NCDs, especially the periodontal-cardiovascular-diabetes complex. The chapter also discusses the problem of global differences in terms of disease occurrence and availability of healthcare services, highlighting the need for equity-based interventions. It suggests a global policy framework based on SRFA, which involves the integration of oral health in health systems, the enhancement of primary health care, and inter-sectoral cooperation. Therefore, optimal resource allocation and adherence to global health priorities are possible.
