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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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The oncogenic potential of human papillomavirus (HPV) has been widely acknowledged in relation to multiple types of cancer. The objective of this investigation was to conduct a comprehensive assessment of the available evidence pertaining to the correlation between HPV and various types of cancer, such as cervical, colon, ovarian, and head and neck cancers, in the Kingdom of Saudi Arabia (KSA). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were complied with to conduct a systematic literature search aimed at identifying studies that explore the correlation between HPV and the specified cancers. Databases such as Web of Science, Embase, PubMed, and the Cochrane Library were queried up until May of 2023. Relevant literature was obtained, information was extracted, and the methodological rigor was evaluated. The high-risk HPV, namely HPV-16 and HPV-18, were detected as the most prevalent variants in KSA. A significant proportion of cervical cancer cases in the region were found to be associated HPV infection. The molecular tests have furnished evidence that establishes a connection between HPV infection and colonic polyps as well as colorectal cancer. This finding suggests that HPV may have a plausible role in the etiology of these medical conditions. The results of genotyping and integration analyses suggest a probable correlation between HPV and the development of ovarian cancer. Additionally, the prevalence of head and neck squamous cell cancer related to HPV was notably reduced in this particular geographical area. This study presents persuasive findings that establish a connection between HPV and cervical cancer and proposes plausible correlations with squamous cell carcinomas in the colon, ovaries, and head and neck. The aforementioned results emphasize the necessity for additional inquiry into the function of HPV in the onset and advancement of said malignancies. Further investigations are necessary to augment our comprehension of the role of HPV in these neoplasms.
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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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BACKGROUND: Although, approximately 30% of the world's population is estimated to be infected with Toxoplasma gondii (T. gondii) with serious manifestations in immunocompromised patients and pregnant females, the available treatment options for toxoplasmosis are limited with serious side effects. Therefore, it is of great importance to identify novel potent, well tolerated candidates for treatment of toxoplasmosis. The present study aimed to evaluate the effect of Zinc oxide nanoparticles (ZnO NPs) synthesized using Zingiber officinale against acute toxoplasmosis in experimentally infected mice. METHODS: The ethanolic extract of ginger was used to prepare ZnO NPs. The produced ZnO NPs were characterized in terms of structure and morphology using Fourier Transformed Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), UV- spectroscopy and scanning electron microscopy (SEM). The prepared formula was used in treatment of T. gondii RH virulent strain. Forty animals were divided into four groups, with ten mice per group. The first group was the uninfected, control group. The second group was infected but untreated. The third and the fourth groups received ZnO NPs and Spiramycin orally in a dose of 10 mg/kg and 200 mg/kg/day respectively. The effect of the used formulas on the animals survival rate, parasite burden, liver enzymes -including Alanine transaminase (ALT) and aspartate transaminase (AST)-, nitric oxide (NO) and Catalase antioxidant enzyme (CAT) activity was measured. Moreover, the effect of treatment on histopathological alterations associated with toxoplasmosis was examined. RESULTS: Mice treated with ZnO NPs showed the longest survival time with significant reduction in the parasite load in the livers and peritoneal fluids of the same group. Moreover, ZnO NPs treatment was associated with a significant reduction in the level of liver enzymes (ALT, AST) and NO and a significant increase in the antioxidant activity of CAT enzyme. SEM examination of tachyzoites from the peritoneal fluid showed marked distortion of T. gondii tachyzoites isolated from mice treated with ZnO NPs in comparison to untreated group. T. gondii induced histopathological alterations in the liver and brain were reversed by ZnO NPs treatment with restoration of normal tissue morphology. CONCLUSION: The produced formula showed a good therapeutic potential in treatment of murine toxoplasmosis as demonstrated by prolonged survival rate, reduced parasite burden, improved T. gondii associated liver injury and histopathological alterations. Thus, we assume that the protective effect observed in the current research is attributed to the antioxidant capability of NPs. Based on the results obtained from the current work, we suggest greenly produced ZnO NPs as a chemotherapeutic agent with good therapeutic potential and high levels of safety in the treatment of toxoplasmosis.
Subject(s)
Nanoparticles , Parasites , Toxoplasma , Toxoplasmosis , Zinc Oxide , Zingiber officinale , Female , Mice , Animals , Zinc Oxide/therapeutic use , Zinc Oxide/chemistry , Zinc Oxide/pharmacology , Antioxidants , Toxoplasmosis/drug therapy , Toxoplasmosis/parasitology , Nanoparticles/chemistry , Disease Models, AnimalABSTRACT
Background: Mobile phones have become part of everyday life with a potential risk for microbial transmission. Makkah is a mass gathering city that may act as hotspots of disease transmission. The contact between public and both visitors and pilgrims to Makkah can't be overlooked, and any small outbreak within the public can be transmitted rapidly to them. Aim: We aimed to assess knowledge, attitudes, and practices (KAP) of general population towards infection transmission via mobile phones in Makkah and different characteristics relevant to KAP scores. Methods: A cross-sectional web-based survey was conducted on general population in Makkah city using a snowballing sampling method. Participants answered questions about their KAP towards infection transmission via mobile phone. The overall KAP scores were graded as good, fair, and poor and explored against different population characteristics using suitable statistical methods. Results: The study included 385 participants aged 15-64 years. About 88.8% owned personal mobile phone, 3.9% encountering a patient with infections transmitted via mobile phones, and 60.5% know nothing about potential role of mobile phones in infection transmission. Only 16.6% had good knowledge, 64.1% with positive attitudes, and 55.3% reported poor practices. The mean knowledge score was significantly higher among young adults (p = 0.002) and those with higher education (p = 0.005). Their mean attitude and practice scores were significantly higher among older adults (p < 0.001 and p = 0.015), female (p = 0.001 and p = 0.022), and those with higher education (p = 0.036 and p = 0.041) respectively. Conclusion: The overall public knowledge and practices towards the role of mobile phones in infection transmission in Makkah was below average though they have positive attitudes. Raising public awareness is important to decrease the possibility of cross-contamination via mobile phones and to develop adequate preventive strategies in a mass gathering setting like Makkah city.
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BACKGROUND: Previous studies have reported involvement of Toxoplasma gondii (T. gondii) infections in the pathogenesis of some autoimmune diseases, such as polymyositis, rheumatoid arthritis, autoimmune thyroiditis, and Crohn's disease. However, data on the association between T. gondii infections and Type 1 diabetes mellitus (T1DM) are still controversial. Therefore, in the present study, we aimed to investigate the pancreatic pathological changes in mouse models with acute and chronic toxoplasmosis and their association with T1DM. MATERIALS AND METHODS: Three groups (10 mice each) of male Swiss Albino mice were used. One group of mice was left uninfected, whereas the second and third groups were infected with the acute virulent T. gondii RH strain and the chronic less virulent Me49 T. gondii strain, respectively. T. gondii-induced pancreatic pathological changes were evaluated by histopathological examination of pancreatic tissues. Moreover, the expression of insulin, levels of caspase-3, and the pancreatic infiltration of CD8+ T cells were evaluated using immunohistochemical staining. RESULTS: Pancreatic tissues of T. gondii-infected animals showed significant pathological alterations and variable degrees of insulitis. Mice with acute toxoplasmosis exhibited marked enlargement and reduced numbers of islets of Langerhans. However, mice with chronic toxoplasmosis showed considerable reduction in size and number of islets of Langerhans. Moreover, insulin staining revealed significant reduction in ß cell numbers, whereas caspase-3 staining showed induced apoptosis in islets of Langerhans of acute toxoplasmosis and chronic toxoplasmosis mice compared to uninfected mice. We detected infiltration of CD8+ T cells only in islets of Langerhans of mice with chronic toxoplasmosis. CONCLUSIONS: Acute and chronic toxoplasmosis mice displayed marked pancreatic pathological changes with reduced numbers of islets of Langerhans and insulin-producing-ß cells. Since damage of ß cells of islets of Langerhans is associated with the development of T1DM, our findings may support a link between T. gondii infections and the development of T1DM.