Cadherin switch (CS) outlined by downregulation of E-cadherin and upregulation of N-cadherin is an established epithelial-mesenchymal transition (EMT) hallmark, being a common signature in wound healing and carcinogenesis. It is intriguing to explore the EMT-associated CS pattern in precancerous phases as well as variably aggressive bladder cancer categories. In this study, we tested CS signified by a reduction in urothelial cells E-cadherin expression and/or aberrant N-cadherin expression in proliferative epithelial changes (PEC) associating inflammation, nonmuscle-invasive bladder cancer (NMIBC), and muscle-invasive bladder cancer (MIBC). Immunohistochemical study of both E-cadherin and N-cadherin was performed for 60 cases: 15 PEC, 8 NMIBC, and 37 MIBC. CS patterns were analyzed: abnormal CS patterns were expressed as deviated, hybrid, co-negative, and full CS patterns. E-cadherin expression was significantly preserved in PEC (86.7%) followed by NMIBC (62.5%) and then MIBC (37.8%) (P = 0.004), whereas N-cadherin showed obvious aberrant expression in MIBC (51.4%) as compared with PEC (33.3%) and NMIBC (25%). In the MIBC group, abnormal cadherin patterns were the highest (70.3%) and was associated with adverse prognostic indicators. In the context of NMIBC progression to MIBC, combined E and N-cadherin evaluation showed highest sensitivity (70.3%) and NPV (31.3%), whereas aberrant expression of N-cadherin presented highest specificity (75%) and positive predictive value (90.5%). For cancer prediction, combined E-cadherin and N-cadherin evaluation showed the highest sensitivity (64.4%); abnormal E-cadherin offered highest specificity (86.7%), positive predictive value (92.9%), and negative predictive value (40.6%). In posttherapy follow-up setting, a metastable EMT signature in the form of partial CS was noted and might reflect resistant dormant populations.
Background: Cryptosporidium species are zoonotic opportunistic coccidian parasites that could cause disseminated life-threatening infection in the immunocompromised host. Unfortunately, few available drugs effectively eradicate the infectious oocyst with limited availability in developing countries. Although Nitazoxanide (NTZ) is the drug of choice for the treatment of cryptosporidiosis, it has limited efficacy in malnourished and immunocompromised patients. Moreover, platelet-rich plasma (PRP) successfully ameliorated the hepatic granuloma size in patients with parasitic schistosomiasis mansoni. Objective: This study aims to test the potential therapeutic effect of PRP versus the currently used NTZ, and/or using PRP as adjuvant therapy. Material and Methods: Sixty-five immunosuppressed rats were divided into 5 groups: non-infected as negative control (GI), infected non-treated as the positive control (GII), infected with Cryptosporidium spp. and treated with either intraperitoneal PRP (GIII), or NTZ (GIV), or a combination of intraperitoneal PRP and NTZ (GV). Parameters used for evaluation of the therapeutic efficacy included parasitological examination, histopathological examination of ileocaecal and liver specimens, and quantitative analysis of reduced glutathione (GSH) and malondialdehyde (MDA) for evaluation of oxidative stress markers, glutamic-oxaloacetic transaminase (SGOT), and glutamic pyruvic transaminase (SGPT) for evaluation of liver functions. Results: Parasitological and histopathological examinations revealed minimal improvement in GIII, marked improvement in GIV, and the best results were recorded in GV. The administration of PRP in GIII produced no significant changes in GSH, MDA, SGOT compared to positive control GII. Treatment with NTZ in GIV, and in addition to PRP in GV showed significant difference (P<0.05) compared to GII regarding serum results of GSH, MDA, and SGOT with the best results recorded in GV. GIV and GV showed reduction of serum levels of SGPT although there was statistically insignificant difference between the study groups. Conclusion: PRP could be used as a potential adjuvant therapy with NTZ to ameliorate the pathologic and inflammatory effects of cryptosporidiosis on the ileocaecal region. It also improves liver function in the immunocompromised hosts. Platelet-rich plasma in cryptosporidiosisEl-Kholy et al.,
Introduction: Although widespread, BCC is still relatively poorly understood in regards to pathogenesis and prognosis, particularly the lesions formed on anatomical sites away from sun exposure. With the aim of deepening our understanding of the pathogenesis and clinico-pathological correlations of BCCs, we conducted this study. Methods: Tissue blocks and data of 52 Egyptian patients diagnosed with BCC were retrieved for clinical information and inclusion criteria, then re-examined histologically; p16 immunostaining was carried out and evaluated for analysis and comparison between the two groups, i.e., sun-exposed and sun-protected. Results: Sex, age, clinical suspicion, tumor size, recurrence status, and histologic variants did not show a significant difference between the sun-protected and sun-exposed groups; however, the mean ages recorded were 67.2 vs. 62.7 for the sun-protected and sun-exposed groups, respectively. A total of 52% of BCCs were positive for p16. The sun-protected lesions showed p16 positivity in 61% of cases, whereas 49% of the sun-exposed lesions were positive with no significant difference. There was a significant difference in p16 expression between the recurrent and non-recurrent lesions. Conclusions: A significant difference was seen in the case of cancer recurrence, where all the recurrent BCCs in this study demonstrated negative p16 immunostaining of the primary lesions; however, the positively stained cases in total were 52% of BCCs. The mean patient age of the sun-protected group was much higher than in previous peer studies. We assume that the biological, prognostic, and clinical aspects of p16 protein expression in BCCs are still far from being clearly understood. Further studies are highly recommended, with more focus on its role in the pathogenesis and the prognostic factors.
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are self-renewing, clonal precursors of non-haematopoietic tissues, with anti-inflammatory and anti-apoptotic effect. This study aimed to evaluate the effect of BM-MSCs on chronic toxoplasmosis. BM-MSCs were isolated from 6-wk-old BALB/c donor male mice, then grown and propagated in culture until cell count was 5–8x106/ml. Female Swiss albino mice were divided into five groups: Group I (infected mice injected with BM-MSCs); Group II (infected mice treated with both BM-MSCs and conventional treatment); Group III (infected mice conventionally treated with Spiramycin-Metronidazole combination); Group IV (infection control group in which mice were infected with Me49 strain of Toxoplasma gondii) and Group V (non-infected mice injected with BM-MSCs). Histopathological examination of brain tissue and survival rate were assessed in each group. Compared to the infection control group and conventionally treated group, the infected mice injected with BM-MSCs showed less tissue damage, mild inflammatory changes in brain sections and low mortality rate. The group treated with both MSCs and conventional treatment showed unexpected sever inflammation and the highest mortality rate.
Background: Schistosomiasis is a major health problem infecting about 7.2 million in Egypt. Praziquantel (PZQ) is the only drug effective against Schistosoma mansoni infection without effective available alternatives. VEGF was used to assess the associated schistosomal inflammatory and hepatic histopathological changes. Aim of Study:The aim of this work is to evaluate the expression of VEGF in hepatocytes and sinusoids of experimental infected mice with Schistosomiasis mansoni comparative to treated group with PZQ.
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