Vol 30, No 15 (2024)

CRISPR and gene editing technologies have emerged as transformative tools in medicine, offering unprecedented precision in targeting genetic disorders and revolutionizing drug development. This review explores the multifaceted impact of CRISPR across various medical domains, from hereditary diseases to infectious diseases and cancer. The potential of CRISPR in personalized medicine, therapeutic innovation, and pandemic prevention is highlighted, along with its role in reshaping traditional drug development processes. However, alongside its promise, ethical considerations loom large, particularly regarding germline editing and equitable access to treatments. The commercialization of CRISPR poses further challenges, raising questions about affordability and healthcare equity. Collaboration among scientists, policymakers, and the public is emphasized to navigate the ethical and societal implications of CRISPR responsibly. As the field advances, it is essential to ensure that the benefits of CRISPR are realized while addressing potential risks and maintaining a commitment to the well-being of future generations.

:The SARS-CoV-2 virus emerged towards the end of 2019 and caused a major worldwide pandemic lasting at least 2 years, causing a disease called COVID-19. SARS-CoV-2 caused a severe infection with direct cellular toxicity, stimulation of cytokine release, increased oxidative stress, disruption of endothelial structure, and thromboinflammation, as well as angiotensin-converting enzyme 2 (ACE2) down-regulation-mediated renin-angiotensin system (RAS) activation. In addition to glucosuria and natriuresis, sodium-glucose transport protein 2 (SGLT2) inhibitors (SGLT2i) cause weight loss, a decrease in glucose levels with an insulin-independent mechanism, an increase in erythropoietin levels and erythropoiesis, an increase in autophagy and lysosomal degradation, Na+/H+-changer inhibition, prevention of ischemia/reperfusion injury, oxidative stress and they have many positive effects such as reducing inflammation and improving vascular function. There was great anticipation for SGLT2i in treating patients with diabetes with COVID-19, but current data suggest they are not very effective. Moreover, there has been great confusion in the literature about the effects of SGLT2i on COVID-19 patients with diabetes . Various factors, including increased SGLT1 activity, lack of angiotensin receptor blocker co-administration, the potential for ketoacidosis, kidney injury, and disruptions in fluid and electrolyte levels, may have hindered SGLT2i's effectiveness against COVID-19. In addition, the duration of use of SGLT2i and their impact on erythropoiesis, blood viscosity, cholesterol levels, and vitamin D levels may also have played a role in their failure to treat the virus. This article aims to uncover the reasons for the confusion in the literature and to unravel why SGLT2i failed to succeed in COVID-19 based on some solid evidence as well as speculative and personal perspectives.

Background:Metabolism of oral anticoagulants (OAC) is affected by P-glycoprotein (P-gp)/ CYP3A4 enzyme. However, the P-gp/CYP3A4 inhibitors are unavoidably used with OACs.

Methods:Medline, Cochrane, and Embase were systematically searched for randomized controlled trials and cohort studies from inception till 23rd November, 2022 to assess the safety and effectiveness of OACs when concomitantly used with P-gp/CYP3A4 inhibitors. The primary outcomes were major bleeding and gastrointestinal (GI) bleeding. Secondary outcomes were stroke/systemic embolism (SE), all-cause mortality, any bleeding as well as intracranial hemorrhage (ICH). We estimated summary odds ratios (OR) with 95% credible intervals (CI) using pairwise and network meta-analysis with random effects

Results:A total of 11 studies involving 37,973 patients were included. When concomitantly used with P-pg/ CYP3A4 inhibitors, network meta-analysis indicated that dabigatran, apixaban, and edoxaban were associated with significantly lower risk of major bleeding compared to rivaroxaban, with ORs of 0.56, 0.51 and 0.48, respectively. Rivaroxaban and dabigatran were associated with a significantly increased risk of GI bleeding than warfarin, apixaban and edoxaban. Dabigatran and apixaban were linked with significantly lower risk of any bleeding compared with warfarin (ORs were 0.75 and 0.68, respectively) or rivaroxaban (ORs were 0.67 and 0.60, respectively). Apixaban (OR 0.32) and edoxaban (OR 0.35) were associated with a lower risk of ICH compared with warfarin. There was no difference between any OACs in terms of stroke/SE or all-cause mortality.

Conclusion:When concomitantly used with P-gp/CYP3A4 inhibitors, apixaban and edoxaban were associated with a lower risk of bleeding, though no significant difference in effectiveness was observed among all OACs.

Background:After implementing the two-child policy, more Chinese women who had a previous delivery had their second child. Nevertheless, the impacts of parity on Gestational Diabetes (GDM) and macrosomia have not been fully confirmed. Therefore, we aimed to analyse the characteristics of pregnancy by parity and evaluate the association of parity with risks of GDM/macrosomia in a Chinese population.

Methods:A total of 193,410 pregnant women (including 148,293 primiparae and 45,117 multiparae) with complete information were included. Univariate and multivariate logistic regression analyses were used to examine the association between parity and risks of GDM/macrosomia.

Results:With the gradual implementation of the two-child policy, the proportion of multiparae increased rapidly and then decreased slightly. Multiparae were more likely to be older and have higher intrapartum BMI, as compared to primiparae (p < 0.001). Univariate regression analyses suggested that parity could increase the risks of GDM and macrosomia; while after adjustment, the association between parity and GDM risk disappeared, and the effects of parity on macrosomia risk and birth weight of babies were also weakened. Further, stratified analysis showed that parity only increased the risk of GDM in women over 30 years, and the effects of parity on macrosomia risk and birth weight were more pronounced among women over 30 years compared to women under 30 years.

Conclusion:Parity was not associated with GDM risk, but mildly associated with macrosomia risk. Particular attention should be paid to multiparae with advanced age to reduce the risks of GDM and macrosomia.

A typographical error appeared in author's affiliation in the article titled "N-unsubstituted Imidazoles: Design, Synthesis, and Antimicrobial Evaluation", published in Current Pharmaceutical Design, 2023; 29(23): 1875-1881 [1]. Details of the error and a correction are provided below. Original: Author Affiliation: ¹Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Tehran Islamic Azad Medical Sciences University, Tehran, Iran. Corrected: Author Affiliation: ¹Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. We regret the error and apologize to readers. The original article can be found online at: https://www.eurekaselect.com/article/133413