Metformin mitigates dementia risk among individuals with type 2 diabetes.

This mini-narrative review explores the relationship between diabetes and dementia, focusing on the potential mitigating role of metformin in reducing cognitive decline among individuals with type 2 diabetes. The interplay of factors such as glycemic control, diabetic complications, and lifestyle influences characterises diabetes-related dementia. This review emphasises the significance of comprehensive diabetes management in addressing the heightened risk of dementia in this population. Methodologically, the review synthesises evidence from 23 studies retrieved through searches on PubMed, Embase, Google Scholar, and Scopus. Current evidence suggests a predominantly positive association between metformin use and a reduced risk of dementia in individuals with diabetes. However, the review shows the complex nature of these outcomes, revealing variations in results in some studies. These discrepancies show the importance of exploring dose-response relationships, long-term effects, and demographic diversity to unravel the complexities of metformin's impact on cognitive health. Limitations in the existing body of research, including methodological disparities and confounding variables, necessitate refined approaches in future studies. Large-scale prospective longitudinal studies and randomised controlled trials focusing specifically on cognitive effects are recommended. Propensity score matching and exploration of molecular mechanisms can enhance the validity of findings in clinical practice. From a clinical perspective, metformin can serve as a potential adjunctive therapy for individuals with diabetes at risk of cognitive decline.

Mental health challenges in Nigeria: Bridging the gap between demand and resources.

This study discusses the significant topic of mental health challenges in Nigeria, focusing on the shortage of mental health professionals, particularly psychiatrists, and the factors influencing medical students' hesitation to pursue psychiatry as a career path. We examine the multifaceted difficulties in Nigeria's mental health environment using various sources, including research studies and statistical data. The scarcity of psychiatrists, with only 250 for a population of 200 million, underscores the urgent need for attention to mental health within the country. Factors such as brain drain, inadequate learning infrastructure, limited research exposure and insufficient health coverage contribute to this crisis. Additionally, societal stigma and financial constraints discourage students from pursuing psychiatry as a career. To address these challenges comprehensively, we propose a holistic approach that involves cross-disciplinary collaboration, robust mental health education in all healthcare programs, community-based awareness initiatives and transdisciplinary teamwork among mental health providers. We highlight the importance of mentorship, scholarships and national advocacy to encourage more individuals to enter the mental health profession, emphasizing the need for diversity and inclusiveness. Furthermore, our paper stresses the significance of research and innovation in advancing mental health treatment and inspiring passion for mental health among students and aspiring professionals. By embracing this comprehensive set of recommendations, we aim to cultivate a diverse, talented and compassionate workforce capable of effectively addressing Nigeria's pressing mental health challenges.

M1 polarization bias and subsequent nonalcoholic steatohepatitis progression is attenuated by nitric oxide donor DETA NONOate via inhibition of CYP2E1-induced oxidative stress in obese mice.

Activation of M1 macrophages in nonalcoholic steatohepatitis (NASH) is produced by several external or endogenous factors: inflammatory stimuli, oxidative stress, and cytokines are known. However, any direct role of oxidative stress in causing M1 polarization in NASH has been unclear. We hypothesized that CYP2E1-mediated oxidative stress causes M1 polarization in experimental NASH, and that nitric oxide (NO) donor administration inhibits CYP2E1-mediated inflammation with concomitant attenuation of M1 polarization. Because CYP2E1 takes center stage in these studies, we used a toxin model of NASH that uses a ligand and a substrate of CYP2E1 for inducing NASH. Subsequently, we used a methionine and choline-deficient diet-induced rodent NASH model where the role of CYP2E1 in disease progression has been shown. Our results show that CYP2E1 causes M1 polarization bias, which includes a significant increase in interleukin-1ß (IL-1ß) and IL-12 in both models of NASH, whereas CYP2E1-null mice or diallyl sulfide administration prevented it. Administration of gadolinium chloride (GdCl3), a macrophage toxin, attenuated both the initial M1 response and the subsequent M2 response, showing that the observed increase in cytokine levels is primarily from macrophages. Based on the evidence of an adaptive NO increase, the NO donor administration in vivo that mechanistically inhibited CYP2E1 catalyzed the oxidative stress during the entire study in NASH-abrogated M1 polarization and NASH progression. The results obtained show the association of CYP2E1 in M1 polarization, and that inhibition of CYP2E1 catalyzed oxidative stress by an NO donor (DETA NONOate [(Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate]) can be a promising therapeutic strategy in NASH.