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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]

Objective: Lupus nephritis (LN) is a significant consequence of systemic lupus erythematosus (SLE). To the best of our knowledge, this is the first work that focuses on evaluation of serum interleukin (IL-) 21 as a diagnostic biomarker of LN activity, compared to B lymphocyte stimulator (BlyS), tumor necrosis factor ligand superfamily member 13 (TNF-SF13), and traditional techniques of active LN attempting to compare their diagnostic usefulness. Methods: Serum levels of IL-21, BlyS, and TNF-SF13 during LN were investigated. Twenty-five biopsy-proven, active LN female patients and 15 SLE patients without active LN and 20 healthy controls (HCs) joined this work. Results: Serum IL-21 level was significantly higher in active LN group than in inactive LN group. Correlation analysis showed that serum IL-21 levels were significantly correlated with total SLEDAI (r = 0.41, p = 0.03), renal-SLEDAI (r = 0.48, p = 0.04), renal activity index (AI) (r = 0.93; p < 0.001), and 24-h proteinuria (r = 0.51; p > 0.008). Receiver operating characteristic curve (ROC) revealed the ability of serum IL-21 to discriminate between active and inactive LN with 70% sensitivity at >240 pg/ml cutoff point (AUC 0.809). Conclusion: For Egyptian SLE patients, serum levels of IL-21 were superior to TNF-SF13 and BlyS and correlated significantly with the activity indexes of LN, indicating a promising role as a potential biomarker of active LN. [ABSTRACT FROM AUTHOR]

For thousands of years, garlic (Allium sativum Linnaeus) has been consumed in food and health by numerous civilizations. Cryptosporidium (C.) parvum is an apicomplexan parasite that causes a gastrointestinal disease, with the most common symptoms being watery diarrhea. Although several substances have been tried for its anti-cryptosporidial action, there is no effective treatment for Cryptosporidium disease, especially in immunocompromised individuals. The present study aimed firstly to characterize the bio-active compounds in Allium sativum L. and secondly to evaluate its efficacy as a therapy for cryptosporidiosis especially in immunocompromised mice. This was accomplished by evaluating the parasitological and histopathological parameters in the experimentally infected immunocompetent and immunocompromised mice. Also, the cytokine profile during the experimental time was recorded through the measuring of T helper (h)1, Th2 and Th17 cells cytokines. Immunosuppressed mice were given 0.25 μg/g per day of dexamethasone orally, before infection with Cryptosporidium parvum oocysts, for fourteen consecutive days. Starting 10 days post infection (PI), nitazoxanide (100 mg/kg per day) or Allium sativum (50 mg/kg per day) was given orally for fourteen consecutive days. Our results showed that oocyst shedding, on the 32nd day PI, in immunocompromised infected group treated with Allium sativum (354.11, 99.35% PR) showed a significant decrease when compared to its corresponding group treated with nitazoxanide (4369.14, 92.05% PR). On the 32nd day PI, all cytokines levels have been decreased to levels that were similar to those of their uninfected corresponding control groups; also, the histopathological changes and the loss in animals' body weight had been improved. Treatment with nitazoxanide did not result in infection clearance or a reduction in the increased cytokines' levels. Allium sativum L. displayed high efficacy as a potential therapeutic agent against Cryptosporidium , which supports its traditional usage in parasite diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

Cryptosporidiosis is a worldwide health problem that results in an economic loss. The disease is caused by the protozoan Cryptosporidium spp. Individuals with suppressed immunity, like those with organ transplantation, cancer and human immunodeficiency virus syndrome, suffer from the infection that may lead to the death. Nitazoxanide (NTZ) is the approved FDA treatment for cryptosporidiosis in immunocompetent individuals. There is an urgent need to find a new natural treatment that can replace NTZ in immunosuppressed hosts. The study aimed to use grape seed extract loaded chitosan nanoparticles (GSEx-CHNPs) in treatment of cryptosporidiosis in immunosuppressed male mice. GSEx was prepared by the alcoholic extraction method followed by the identification of its bioactive components. GSEx-CHNPs were synthesized by ionic gelation method and physically characterized then their activities were examined in vitro. The experimental groups, included immunocompetent and immunosuppressed groups, was treated with NPs for 14 days post infection (PI). The results showed the presence of many phenolic compounds in the GSEx. GSEx-CHNPs significantly improved the loss in animals body weight, cleared the infection and amolerated the serum cytokines levels. GSEx-CHNPs showed anti-cryptosporidial activity especially in immunosuppressed mice model. Where, it amolerated the disturbance in the cytokine profile leading to an anti-inflammatory response., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

Introduction. Cryptosporidium parvum causes intestinal parasitic infections affecting both immunosuppressed and immunocompetent individuals. Gap statement. Given the absence of effective treatments for cryptosporidiosis, especially in immunodeficient patients, the present study was designed to assess the therapeutic efficacy of secnidazole (SEC) and its combination with nitazoxanide (NTZ) in comparison to single NTZ treatment in relation to the immune status of a murine model of C. parvum infection. Methodology. The infected groups were administered NTZ, SEC or NTZ-SEC for three or five successive doses. At days 10 and 12 post-infection (p.i.), the mice were sacrificed, and the efficacy of the applied drugs was evaluated by comparing the histopathological alterations in ileum and measuring the T helper Th1 (interferon gamma; IFN-γ), Th2 [interleukin (IL)-4 and IL-10] and Th17 (IL-17) cytokine profiles in serum. Results. The NTZ-SEC combination recorded the maximal reduction of C. parvum oocyst shedding, endogenous stages count and intestinal histopathology, regardless of the immune status of the infected mice. The efficacy of NTZ-SEC was dependent on the period of administration, as the 5 day-based treatment protocol was also more effective than the 3 day-based one in terms of immunocompetence and immunosuppression. The present treatment schedule induced an immunomodulatory effect from SEC that developed a protective immune response against C. parvum infection with reduced production of serum IL-17, IFN-γ, IL-4 and IL-10. Conclusions. Application of NTZ-SEC combined therapy may be useful in treatment of C. parvum , especially in cases involving immunosuppression.

Cystic hydatid disease (Hydatidosis) is one of the most important parasitic zoonoses and remains a public health and economic problem all over the world. Cyst fluid was obtained from hepatic and pulmonary cysts for demonstration of protoscolices and hooklets. Therefore, a standardized and approachable diagnostic tool for the serodiagnosis of CE is still needed. Dot-ELISA is a solid phase diagnostic method for detection of antigen or antibody that is used widely for diagnosis of protozoan and metazoan diseases of human and animals. In the present study, E. granulosus protoscolex antigen was early detected in patient sera using Dot-ELISA, PAb was prepared from anti-rabbit sera and used for coating and as conjugate in Dot-ELISA technique. 48 patients out of 50 were positive to E. spp. with sensitivity and specificity 96% and 94%, respectively. The PPV was 94% and NPV was 90%. Finally, the present results showed that the Dot-ELISA was easy to perform, not expensive, safe, and with good sensitivity and specificity.

Toxoplasmosis is one of the most world-wide spread zoonosis representing a very serious clinical and veterinary problem. Although rare, congenital toxoplasmosis can cause severe ne- urological or ocular disease (leading to blindness) as well as cardiac and cerebral anomalies. Prenatal care must include education about prevention of toxoplasmosis. Thus, a standardized and approachable diagnostic tool for the serodiagnosis of toxoplasmosis is still needed. Serological tests are the most widely used biological tools for the diagnosis of toxoplasmosis worldwide. Sandwich-ELISA is a solid phase diagnostic method for detection of antigen or antibody that is used widely for diagnosis of protozoan and metazoan diseases of human and animals. In the present study, T. gondii SAG2 antigen was early detected in patient sera using Ssndwich-ELISA, PAb was prepared from anti-rabbit sera and used for coating and as conjugate in Sandwich-ELISA technique. 46 patients out of 50 were positive to Toxoplsama spp. with sensitivity and specificity 92% and 90%, respectively. The PPV was 90.2% and NPV was 83.3%. Finally, the result of our study showed that the Sandwich-ELISA designed in our study is easy to perform, not expensive, safe, and simple with good sensitivity and specificity.

Nanotechnology is important for medical diagnosis. Various nanoparticles have presented tremendous potential for diagnosing disease markers, pre-cancerous cells, fragment of viruses, specific proteins, antibodies, and other disease indicators. In general, nanoparticles are smaller than 1,000 nm and produced from different materials in different shapes such as spheres, rods, wires, and tubes. Our study aimed to develop a novel antigen-capture immunoassay based on IgG polyclonal antibody-coated magnetic microbead nanoparticles for the rapid detection of circulating surface antigen 1 of Toxoplasma gondii in human serum samples. Sandwich ELISA elicited a sensitivity of 92%, a specificity of 92.7%, a positive predictive value (PPV) of 92%, and a negative predictive value (NPV) of 92.7%. Immunomagnetic bead-ELISA showed sensitivity (98%), specificity (96.4%), PPV (96%), and NPV (98.1%) higher than that of sandwich ELISA. It is obvious that the use of magnetic microbead nanoparticles offers the potential advantage of improving the diagnostic testing of toxoplasmosis.