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Combining immune checkpoint inhibitors, specifically nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4), holds substantial promise in revolutionizing cancer treatment. This review explores the transformative impact of these combinations, emphasizing their potential for enhancing therapeutic outcomes across various cancers. Immune checkpoint proteins, such as PD1 and CTLA4, play a pivotal role in modulating immune responses. Blocking these checkpoints unleashes anticancer activity, and the synergy observed when combining multiple checkpoint inhibitors underscores their potential for enhanced efficacy. Nivolumab and ipilimumab harness the host's immune system to target cancer cells, presenting a powerful approach to prevent tumor development. Despite their efficacy, immune checkpoint inhibitors are accompanied by a distinct set of adverse effects, particularly immune-related adverse effects affecting various organs. Understanding these challenges is crucial for optimizing treatment strategies and ensuring patient well-being. Ongoing clinical trials are actively exploring the combination of checkpoint inhibitory therapies, aiming to decipher their synergistic effects and efficacy against diverse cancer types. This review discusses the mechanisms, adverse effects, and various clinical trials involving nivolumab and ipilimumab across different cancers, emphasizing their transformative impact on cancer treatment.
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[This corrects the article DOI: 10.3389/fvets.2024.1374116.].
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Background: Cryptosporidiosis is an opportunistic parasitic disease widely distributed worldwide. Although Cryptosporidium sp. causes asymptomatic infection in healthy people, it may lead to severe illness in immunocompromised individuals. Limited effective therapeutic alternatives are available against cryptosporidiosis in this category of patients. So, there is an urgent need for therapeutic alternatives for cryptosporidiosis. Recently, the potential uses of Eugenol (EUG) have been considered a promising novel treatment for bacterial and parasitic infections. Consequently, it is suggested to investigate the effect of EUG as an option for the treatment of cryptosporidiosis. Materials and methods: The in silico bioinformatics analysis was used to predict and determine the binding affinities and intermolecular interactions of EUG and Nitazoxanide (NTZ) toward several Cryptosporidium parvum (C. parvum) lowa II target proteins. For animal study, five groups of immunosuppressed Swiss albino mice (10 mice each) were used. Group I was left uninfected (control), and four groups were infected with 1,000 oocysts of Cryptosporidium sp. The first infected group was left untreated. The remaining three infected groups received NTZ, EUG, and EUG + NTZ, respectively, on the 6th day post-infection (dpi). All mice were sacrificed 30 dpi. The efficacy of the used formulas was assessed by counting the number of C. parvum oocysts excreted in stool of infected mice, histopathological examination of the ileum and liver tissues and determination of the expression of iNOS in the ileum of mice in different animal groups. Results: treatment with EUG resulted in a significant reduction in the number of oocysts secreted in stool when compared to infected untreated mice. In addition, oocyst excretion was significantly reduced in mice received a combination therapy of EUG and NTZ when compared with those received NTZ alone. EUG succeeded in reverting the histopathological alterations induced by Cryptosporidium infection either alone or in combination with NTZ. Moreover, mice received EUG showed marked reduction of the expression of iNOS in ileal tissues. Conclusion: Based on the results, the present study signified a basis for utilizing EUG as an affordable, safe, and alternative therapy combined with NTZ in the management of cryptosporidiosis.
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INTRODUCTION: To date few studies have investigated the correlation between inflammatory markers and lipoproteins in the serum of age-related macular degeneration (AMD) patients, often reporting conflicting findings. This study aimed to investigate the correlation between lipid analytes and C-reactive protein (CRP) levels in individuals diagnosed with dry AMD. METHODS: A standard clinical lipid panel (total cholesterol, triglycerides, high-density lipoprotein [HDL], and low-density lipoproteins) and CRP laboratory results were retrospectively collected from the medical records of patients with dry AMD and age- and sex-matched controls. RESULTS: The study included 90 patients with dry AMD and 270 patients without AMD. In univariate analysis, CRP showed a higher mean value in cases than in controls. After adjusting for age and sex, CRP and triglyceride levels showed significant differences between cases and controls. Pearson's correlation analysis revealed a significant negative correlation between CRP and HDL levels in the dry AMD group (n=90). Other lipid analytes showed no significant correlations with CRP. CONCLUSION: Our findings add to the growing body of evidence linking inflammation to AMD. Although it is unclear whether changes in serum CRP and triglyceride levels are the causes or effects, monitoring both analytes may be beneficial as an early disease predictor, especially in individuals with a family history of AMD. The negative correlation between CRP and HDL (i.e., inflammation and good cholesterol) may be targeted for future therapies.