Comparison of tissue biomarkers between non-schistosoma and schistosoma-associated urothelial carcinoma.

BACKGROUND: High-grade urothelial carcinoma either non-Schistosoma (NS-UBC) or Schistosoma (S-UBC)-associated is the tenth cause of death worldwide and represents a serious therapeutic problem. AIM: Evaluation of the immmunohistochemical expression of tumor necrosis factor-alpha (TNFα), epidermal growth factor receptor (EGFR), programmed cell death protein-1 (PDL1), estrogen receptor-alpha (ERα) and UroplakinIII, in the high-grade in NS-UBC and S-UBC as potential prognostic and therapeutic targets analyzed through estimation of area percentage, optical density and international pathological scoring system for each marker. MATERIAL AND METHODS: Sixty high grade urothelial carcinoma cases were enrolled in the study (30 cases of NS-UBC and 30 cases of S-UBC). The cases were immunohistochemically-assessed for TNFα, EGFR, PDL1, ERα and Uroplakin III expression. In S-UBC, parasite load was also evaluated for correlation with the immunohistochemical markers' expression in S-UBC. RESULTS: The area percentage of immune-expression of TNFα and EGFR was higher in S-UBC compared to NS-UBC. On the other hand, the NS-UBC displayed statistically-higher expression of PDL1 and uroplakinIII (p-value <0.001). ERα revealed higher, yet, non-significant expressions in S-UBC compared to NS-UBC (p-value =0.459). PDL1 expression showed the most superior record regarding area percentage (64.6± 34.5). Regarding optical density, TNF-α showed the highest transmittance expression (2.4 ± 0.9). EGFR positively correlated with PDL1 in S-UBC (r= 0.578, p-value =0.001) whereas in NS-UBC, TNFα and PDL1 (r=0.382, p-value=0.037) had positive correlation. Schistosoma eggs in tissues oppose uroplakin III expression and trigger immunomodulation via PDL1. CONCLUSION: Due to lower UroplakinIII expression, S-UBC is supposed to have a poorer prognosis. Hormonal therapy is not hypothesized due to a very minimal ERα expression in both NS-UBC and S-UBC. Regarding immunotherapy, anti-TNF-α is suggested for S-UBC whilst in NS-UBC, blockading PDL1 might be useful. Targeted EGFR therapy seems to carry emphasized outcomes in S-UBC. Correlations encourage combined immune therapy in NS-UBC; nevertheless, in S-UBC, combined anti-EGFR and PDL1 seem to be of benefit.

Impact of Escherichia coli, Candida non-albicans, and Trichomonas vaginalis on Semen Chemical and Functional Parameters: an In-Vitro Study.

BACKGROUND: Infertility is a worldwide medical issue in which infection is recognized to play a major role. Pathogens trigger various mechanisms that impact fertility, either directly by affecting the physiological indices of semen or indirectly by disrupting the process of spermatogenesis. In the current work, the effect of in-vitro cultivation of Escherichia coli (E. coli), Candida non-albicans (C. non-albicans), and Trichomonas vaginalis (T. vaginalis) (as the most frequently reported sexually transmitted infections) was assessed on the physiological functions of the spermatozoa and the chemical characteristics of the seminal fluid. METHOD: The semen samples were exposed to cultures of E. coli, C. non-albicans, and T. vaginalis. The study analyzed the changes in motility, agglutination, viability, DNA fragmentation index (DFI%), seminal pH, and biochemical parameters at 1/2, 1, 1.5, 2, 2.5, 3.5 and 4 hours. RESULTS: Incubation of the semen samples with E. coli resulted in a progressive increase in agglutination, pH, and nitrite. The seminal glucose and the sperm motility, on the other hand, were reduced. The sperm vitality and seminal protein remained unaffected. C. non-albicans induced three forms of agglutination (head-to-head, tail-to-tail, and head-to-tail), lowered pH values and decreased the sperm motility, but did not alter the seminal protein, glucose, nitrite, nor the spermatozoa viability at the different tested time intervals. T. vaginalis resulted in increased seminal protein, and reduced glucose, pH, and motility. It also induced minimal agglutination and caused unchanged nitrite and sperm viability. The DFI% was increased in all pathogens with the C. non-albicans showing the highest DNA fragmentation index. CONCLUSION: Urogenital infection with E. coli, C. non-albicans, or T. vaginalis is assumed to affect the quality of semen through DNA fragmentation, agglutination and altered seminal chemical microenvironment.

Microbiota-Parasite Interaction: Implication of Secretory Immunoglobulin A and P2X7 Receptor Signaling.

The microbiota community is composed of bacteria, fungi, viruses, and protists that exert symbiotic effects within the human body. Unlike microbiota, parasites are characteristically reliant on their hosts to thrive and flourish, producing toxic metabolites that agitate microbiota and disturb homeostasis. The proper management of parasitic infections addresses several important challenges related to low socioeconomic status and emergent resistance. Therefore, understanding the microbiota's role in interactions with hosts and parasites is crucial for managing parasite diseases with fewer economic and adverse effects associated with pharmaceutical interventions. The current review was divided into three sections. Section 1 focused on the mutual microbiota-host interaction through the purinergic P2X7 receptor (P2X7R) and secretory immunoglobulin A (SIgA). The P2X7R is an abundant intestinal cation channel that is crucial in mucosal immunity, facilitated by SIgA-mediated protection in both innate and adaptive immunity. This study demonstrated that microbiota continually "teach and train" host immunity to attain homeostasis via SIgA production (in T cell-independent and T cell-dependent pathways) and the purinergic receptor P2X7R. In addition, we discussed the potential of manipulating SIgA and P2X7R in immune therapies targeting parasitic infections. Section 2 exhibited parasite-microbiota (microbe-microbe) interactions wherein each can indirectly affect one another through physical and immunogenic alterations and directly via predation, bactericidal protein production, and overlapping of nutrient resources. Thus, microbe-microbe interactions appeared to be multifaceted and species-dependent. Section 3 showed the relationship between microbiota and specific parasites, and the promising role of probiotics. In this section, the review discussed examples of tissue, blood, gastrointestinal, genitourinary, and respiratory parasitic diseases, while highlighting the associated dysbiosis. Furthermore, Section 3 acknowledged the importance of "strain-dependent" biotherapy to boost beneficial microbiota, modulate immunity, and exert anti-parasitic effects.

Effects of Lactobacilli acidophilus and/or spiramycin as an adjunct in toxoplasmosis infection challenged with diabetes.

The current study assessed the anti-parasitic impact of probiotics on Toxoplasma gondii infection either solely or challenged with diabetes in Swiss albino mice. The study design encompassed group-A (diabetic), group-B (non-diabetic), and healthy controls (C). Each group was divided into infected-untreated (subgroup-1); infected and spiramycin-treated (subgroup-2); infected and probiotic-treated (subgroup-3); infected and spiramycin+ probiotic-treated (subgroup-4). Diabetic-untreated animals exhibited acute toxoplasmosis and higher cerebral parasite load. Overall, various treatments reduced intestinal pathology, improved body weight, and decreased mortalities; nevertheless, probiotic + spiramycin exhibited significant differences. On day 7 post-infection both PD-1 and IL-17A demonstrated higher scores in the intestine of diabetic-untreated mice compared with non-diabetics and healthy control; whereas, claudin-1 revealed worsening expression. Likewise, on day 104 post-infection cerebral PD-1 and IL-17A showed increased expressions in diabetic animals. Overall, treatment modalities revealed lower scores of PD-1 and IL-17A in non-diabetic subgroups compared with diabetics. Intestinal and cerebral expressions of IL-17A and PD-1 demonstrated positive correlations with cerebral parasite load. In conclusion, toxoplasmosis when challenged with diabetes showed massive pathological features and higher parasite load in the cerebral tissues. Probiotics are a promising adjunct to spiramycin by ameliorating IL-17A and PD-1 in the intestinal and cerebral tissues, improving the intestinal expression of claudin-1, and efficiently reducing the cerebral parasite load.

Histological and immunological insights to hydatid disease in camels.

PURPOSE: To investigate the immuno-histological evidences in viable and non-viable hydatid cysts obtained from naturally infected camels. METHODS: A cohort study (February 2018-December 2019), a total of 15 hydatidosis-infected camels from slaughter houses in Cairo were involved. Specimens were investigated for parasite viability, liver histological changes, IL-17A cytokine immunohistochemical expressions in the adventitial layer, and the anti-nuclear antibodies (ANAs) immunofluorescent expression in the metacestode's structures. Real-Time Quantitative -Morphocytometry and SPSS were utilized. RESULTS: Multi-focal lesions and high viability were found in 60% of the cases. Overall accumulation of collagen associated the parasite establishment that involved infiltrations of mononuclear cells with significantly increased IL-17A expression. Interestingly, the ANAs appeared to have a role in the immune-defense against the metacestode showing different patterns. ANAs production correlated with IL-17A expression and the viability of the parasite. CONCLUSION: IL-17A responses in hydatidosis is associated with collagen deposition and ANA production as a sort of anti-parasite immunity in a viability dependent manner.

Validity of urine-CCA cassette test and indirect haem-agglutination assay (IHA) in the detection of schistosomiasis-mansoni infection relative to microscopic examination.

Several immunodiagnostic assays have been commercially presented over the last years as easy diagnostic methods for schistosomiasis using serum or urine samples. The performance of immunochromatographic test (ICT) and indirect hemagglutination assay (IHA) was validated in the identification of active schistosomiasis infection. Detection of circulating cathodic antigen (CCA) of the parasite in urine samples and anti-Schistosoma antibodies in serum using ICT (Urine-CCA Cassette test) and IHA respectively. Proved diagnosis of Schistosoma mansoni infection was defined by the sum of positive results from microscopic examination (Gold standard) and Kato-Katz method. Out of 173 (mean age, 45 ± 10 years; 70 from Giza, 103 from different Egyptian governorates), 9 4 adult patients were infected. Urine-CCA cassette test despite showing high specificity (91.14%) it was of low sensitivity (23.40%). PPVs was 75.86% and NPV was 50.00% and diagnostic accuracy of 54.34%. The IHA showed a sensitivity of 57.45% and specificity of 48.10%. PPVs was 56.84% whereas NPVs was 48.72%. As for diagnostic accuracy, it was 53.18%. Urine-CCA Cassette test had lower sensitivity than expected for detection of circulating antigen and the IHA kit is generally more expensive than microscopic examination and Urine-CCA cassette test with low sensitivity and specificity. On the basis of this diagnostic performance none of the two tested immune-assays can be a sole tool in the principal diagnosis of active schistosomiasis infections.

Can Toxoplasma gondii Pave the Road for Dementia?

Dementia is an ominous neurological disease. Scientists proposed a link between its occurrence and the presence of Toxoplasma gondii (T. gondii). The long-term sequels of anti-Toxoplasma premunition, chiefly dominated by TNF-α, on the neurons and their receptors as the insulin-like growth factor-1 receptor (IGF-1R), which is tangled in cognition and synaptic plasticity, are still not clear. IGF-1R mediates its action via IGF-1, and its depletion is incorporated in the pathogenesis of dementia. The activated TNF-α signaling pathway induces NF-κß that may induce or inhibit neurogenesis. This study speculates the potential impact of anti-Toxoplasma immune response on the expression of IGF-1R in chronic cerebral toxoplasmosis. The distributive pattern of T. gondii cysts was studied in association with TNF-α serum levels, the in situ expression of NF-κß, and IGF-1R in mice using the low virulent ME-49 T. gondii strain. There was an elevation of the TNF-α serum level (p value ≤ 0.004) and significant upsurge in NF-κß whereas IGF-1R was of low abundance (p value < 0.05) compared to the controls. TNF-α had a strong positive correlation with the intracerebral expression of NF-κß (r value ≈ 0.943, p value ≈ 0.005) and a strong negative correlation to IGF-1R (r value -0.584 and -0.725 for area% and O.D., respectively). This activated TNF-α/NF-κß keeps T. gondii under control at the expense of IGF-1R expression, depriving neurons of the effect of IGF-1, the receptor's ligand. We therefore deduce that T. gondii immunopathological reaction may be a road paver for developing dementia.

The hidden impact of different Blastocystis genotypes on C-3 and IgE serum levels: a matter of debate in asthmatic Egyptian children.

Blastocystis hominis is highly prevalent with respiratory allergies among Egyptian children. Yet, little is known about the possible immunological relationship. Aims of this study were to measure complement-3 (C-3), total and specific IgE to intestinal allergens in patients' serum regarding the identified B. hominis genotypes. In a cross-sectional study, three hundred children (150 asthmatics and 150 non asthmatics) participated in the study from both sexes, mean age 7.5 ± SD (3-4) years after a questionnaire administration. PCR-based genotyping of B. hominis selective in vitro cultivation was performed. C-3, total and specific IgE were all measured in patients' serum utilizing ELISA. Blastocystosis was detected in 100 out of 300 children, 65 (43.3%) out of 150 asthmatics and 35 (23.3%) out of 150 non-asthmatics. Vacuolar forms were the most prevalent in both direct wet mount and stool cultures. Forty (61.5%) out 65 asthmatics and 5 (14.2%) out of 35 non-asthmatics were ≥ 5 organisms/HPF. Sex and irritable bowel disease were statistically insignificant (p value < 0.05). Urticaria was coincided in 15.4% of asthmatics and 8.6% of non-asthmatics. Of 100 cases of blastocystosis, eighty-four were genotype-3 and sixteen were genotype-4. Out of these, 55 cases of genotype-3 and 6 cases of genotype-4 were asthmatics. Positive C-3 serum levels were in 46 (54.81%) of genotype-3 and 2 (12.5%) of genotype-4. High total IgE levels in 30 (35.7%) out of 84 cases of genotype-3 and 4 (25%) out of 16 cases of genotype-4. Positive specific IgE was in 25 (29.8%) of genotype-3 and 3 (18.75%) of genotype-4. Genotype-3 was of higher infection intensity (p value = 0.0001). In conclusion, B. hominis possess a hidden allergy triggering impact that can be obscured by simultaneous high (total and specific) IgE levels towards specific common intestinal allergens. Blastocystosis induces allergy by increasing C-3 serum levels in a genotype-dependent manner being higher in genotype-3. Virulence of genotype-3 seems to stand beyond increased parasite intensity and wide absorption of intestinal allergens that indirectly elevate IgE serum levels.