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Summary: The crosstalk between intestinal epithelial cells (IECs) and Th17-polarized CD4+ T cells is critical for mucosal homeostasis, with HIV-1 causing significant alterations in people living with HIV (PLWH) despite antiretroviral therapy (ART). In a model of IEC and T cell co-cultures, we investigated the effects of IL-17A, the Th17 hallmark cytokine, on IEC ability to promote de novo HIV infection and viral reservoir reactivation. Our results demonstrate that IL-17A acts in synergy with TNF to boost IEC production of CCL20, a Th17-attractant chemokine, and promote HIV trans-infection of CD4+ T cells and viral outgrowth from reservoir cells of ART-treated PLWH. Importantly, the Illumina RNA-sequencing revealed an IL-17A-mediated pro-inflammatory and pro-viral molecular signature, including a decreased expression of type I interferon (IFN-I)-induced HIV restriction factors. These findings point to the deleterious features of IL-17A and raise awareness for caution when designing therapies aimed at restoring the paucity of mucosal Th17 cells in ART-treated PLWH.

Background/aim: Diabetes mellitus (DM) is a serious, chronic and epidemic disease. Its effective therapy with exogenous insulin places an overwhelming burden on the patient's lifestyle. Moreover, pancreatic islet transplantation is limited by the scarceness of donors and the need for chronic immunosuppression. Cell-based therapy is considered an alternative source of insulin-producing cells (IPCs); encapsulating such cellular grafts in immunoisolating devices would protect the graft from immune attack without the need for immunosuppression. Herein, we investigate the ability of TheraCyte capsule as an immunoisolating device to promote the maturation of differentiated rat bone marrow derived mesenchymal stem cells (BM-MSCs), transplanted subcutaneously to treat diabetic rats in comparison with intratesticular transplantation. Main methods: Rat BM-MSC were differentiated into IPCs, and either encapsulated in TheraCyte capsules for subcutaneous transplantation or transplanted intratesticular into diabetic rats. Serum insulin, C-peptide & blood glucose levels of transplanted animals were monitored. Retrieved cells were further characterized by immunofluorescence staining and gene expression analysis. Key findings: Differentiated rat BM-MSC were able to produce insulin in vitro, ameliorate hyperglycemia in vivo and survive for 6 months post transplantation. Transplanted cells induced higher levels of insulin and C-peptide, lower levels of blood glucose in the cured animals of both experimental groups. Gene expression revealed a further in vivo maturation of the implanted cells. Significance: These data suggest that TheraCyte encapsulation of allogeneic differentiated stem cells are capable of reversing hyperglycemia, which holds a great promise as a new cell based, clinically applicable therapies for diabetes.

Background and rationale for the study. Continuing search for suitable tumor-markers is of clinical value in managing patients with various malignancies. These markers may be presented as intracellular substances in tissues or may be released into the circulation and appear in serum. Therefore, this work is concerned with identification and quantitative determination of epithelial membrane antigen (EMA) and fibronectin and estimating their performances as surrogate markers for identifying hepatocellular carcinoma (HCC).Results. A total of 627 individuals constituted this study [fibrosis (F1-F3) = 217; cirrhosis = 191; HCC = 219]. Western-blot was used for identifying EMA and fibronectin in sera. As a result, a single immunoreactive band was shown at 130-kDa and 90-kDa corresponding to EMA and fibronectin, respectively. They were quantified using ELISA providing values in HCC higher than fibrosis or cirrhosis with a significant difference (P < 0.0001). For identifying HCC, EMA showed 0.82 area under receiver-operating characteristic curve (AUC) with sensitivity = 70% and specificity = 78% while fibronectin yielded AUC = 0.70 with sensitivity = 67% and specificity = 82%. FEBA-Test comprising fibronectin and EMA together with total-bilirubin and AFP was constructed yielding AUC = 0.92 for identifying HCC from cirrhosis with sensitivity = 89% and specificity = 85%. FEBA-Test was then tested for differentiating HCC from fibrosis showing AUC = 0.97 with sensitivity = 90% and specificity = 89%. FEBA-Test enabled the correct identification of HCC patients with CLIP 0-1 and size ≤ 3 cm with AUC = 0.80 and AUC = 0.84, respectively, indicating its ability in identifying early HCC.Conclusions. A four-marker index may improve the early detection of HCC with a high degree of accuracy.

Background and rationale for the study. The assessment of liver fibrosis provides useful information not only for diagnosis but also for therapeutic decision. This study was concerned with determining the levels of collagen III and its degrading enzyme matrix metalloproteinase-1 (MMP-1) as direct and complementary markers for liver fibrosis staging.Results. A total of 269 chronic hepatitis C patients constituted this study. Western blotting was used for identifying collagen III and MMP-1 in serum samples. As a result, collagen III and MMP-1 were identified, respectively, at 70 and 245 kDa using their respective mono-specific antibodies. These two markers were quantified in sera of patients using ELISA. Next, Fibro-check was constructed combining collagen III and MMP-1 together with other indirect markers which reflect alteration in hepatic functions that proved useful to stage liver fibrosis. Fibro-check produced area under the receiver-operating characteristic curve (AUC) 0.91 and 0.83 for significant (F2-F4) and cirrhosis (F4), respectively. Additionally, we estimated the performance of Fibro-check in comparison with aspartate to platelet ratio index (APRI) and fibrosis index. Fibro-check seems to be more efficient than both of them. Fibro-check was then applied to the validation study to test its accuracy and reproducibility showing AUCs 0.90 for F2-F4 and 0.86 for F4.Conclusions. Fibro-check combining ‘direct’ and ‘indirect’ markers using a mathematical formula may improve the staging of liver fibrosis with a high degree of accuracy and seems more efficient than APRI and Fibrosis index in this group of Egyptian patients.