Search

Background: Giardia duodenalis and Cryptosporidium parvum are the primary causes of diarrhea with global attention due to the severe pathophysiological changes leading to mortality. During this study, we explored the biological protozoal contaminants (Giardia and Cryptosporidium spp.) in some areas of the Nile River. Then, we evaluated effectiveness of melatonin (Mel) and melatonin loaded lecithin/chitosan nanoparticles (Mel-LCNPs) against giardiasis and cryptosporidiosis in mice models using parasitological and inflammatory response examination. Results: The number of positive samples for Cryptosporidium was higher than that for Giardia with percentage of 46.67% and 40.0%, respectively. Prior to treatment, the physical characterization (hydrodynamic size and zeta potential) and in vitro characterization of Mel-LCNPs were carried. Mel-LCNPs revealed a hydrodynamic size of 78.8 nm and a zeta potential of − 27.2 mV. Furthermore, they have powerful antioxidant and anti-inflammatory properties, while displaying minimal anticoagulant and cytotoxic effects during in vivo evaluation. Mel was consistently discharged from nanoparticles in a regulated and enduring manner for 36 h. Moreover, Mel in NPs has an entrapment efficiency (EE) of 33.6% and a drug loading capacity (DLC) of 7.2% and significant reduction (100% and 99.4%, respectively) in the shedding of Giardia cysts and Cryptosporidium oocysts. This reduction was higher than that observed with Mel alone or LCNPs alone on the 14th day post-infection. Moreover, mice of group V, which received Mel-LCNP treatment, exhibited significantly normal levels of interleukin-4 (IL-4) and interferon-gamma (IFN-γ) as well as healthy control mice group (group I). Conclusion: Mel-LCNPs were highly effective preparations against giardiasis and cryptosporidiosis in Balb/c mice experimentally infected with proved antioxidant, anti-inflammatory, and immunological modulatory characteristics. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus (SLE) is a debilitating rheumatic condition that results in the dysfunction of multiple organs in the body. Atherosclerosis is a common occurrence in people with SLE and is exacerbated by an overabundant of various cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), and their soluble receptors, such as soluble tumor necrosis factor receptor I (sTNFR I) and soluble interleukin-6 receptor (sIL-6R) (known as SLE risk factors) and high concentrations of lipids (known as dyslipidemia risk factors). The intimal medial thickness (IMT) of the internal carotid artery (ICA) is a sonographic measurement that assesses the extent of atherosclerosis. On the other hand, the resistive index (RI) is primarily employed to evaluate the severity of chronic kidney diseases (CKDs), but it is seldom utilized to estimate atherosclerosis in ICA. So, the objective of this study was to conduct retrospective cohort study among SLE patients to define which risk factor, inflammation or dyslipidemia, correlated with the development of atherosclerosis in SLE and which ultrasound assessment, CIMT or RI, is more useful in identifying atherosclerosis. Results: TNF-α, sTNFR I, IL-6, and sIL-6R were significantly elevated (P < 0.0001) in SLE patients (n = 75) compared to the controls (n = 15); also, both CIMT and RI showed significant higher levels in patient's group (P = 0.001 and 0.0025, respectively). Systemic lupus disease activity index (SLEDAI) (P = 0.002), total cholesterol (TC) (P = 0.025), CIMT (P = 0.00045), TNF-α (P < 0.0001), IL-6 (P < 0.0001), sTNFR I (P = 0.006), and sIL-6R (P < 0.0001) rates were significantly higher in atherosclerotic SLE patients (n = 27) than in non-atherosclerotic patients (n = 48). There were clear and meaningful positive correlations (r = 0.82, P = 0.003) observed between CIMT and SLEDAI, as well as between investigated cytokines and their soluble receptors. RI showed no significant differences between two studied groups of patients and also no significant correlations with the studied parameters except with age (r = 0.45, P = 0.035). Conclusion: Inflammation is a more prevalent cause of atherosclerosis than dyslipidemia in SLE, thereby making it a recognized risk factor for SLE. In comparison to RI, CIMT is a valuable sonographic measure for identifying incidence of atherosclerosis. [ABSTRACT FROM AUTHOR]

Cancer remains a formidable global health challenge, with current treatment modalities such as chemotherapy, radiotherapy, surgery, and targeted therapy often hindered by low efficacy and adverse side effects. The indole scaffold, a prominent heterocyclic structure, has emerged as a promising candidate in the fight against cancer. This review consolidates recent advancements in developing natural and synthetic indolyl analogs, highlighting their antiproliferative activities against various cancer types over the past five years. These analogs are categorized based on their efficacy against common cancer types, supported by biochemical assays demonstrating their antiproliferative properties. In this review, emphasis is placed on elucidating the mechanisms of action of these compounds. Given the limitations of conventional cancer therapies, developing targeted therapeutics with enhanced selectivity and reduced side effects remains a critical focus in oncological research. [ABSTRACT FROM AUTHOR]