Autoimmune hepatitis: a study of 50 patients.

INTRODUCTION: Autoimmune hepatitis (AIH) is a well-defined entity in the West but there are sparse Indian data on this disease. AIM: To study the clinical profile and response to treatment of Indian patients with AIH. METHODS: This is a part retrospective and part prospective study of 50 patients (median age 48 years, range 11-82; 43 women) seen between 1995 to 2001, diagnosed to have AIH as per the revised scoring system. Clinical and laboratory profile, response to treatment, and complications of treatment were analyzed. RESULTS: AIH accounted for 6% of all patients with liver disease seen during the period. The presenting symptoms were gastrointestinal in 43 and non-gastrointestinal in 7, with median symptom duration of 6 months (range 2 weeks to 40 years). Forty patients (80%) had chronic liver disease. Associated illnesses were present in 28 patients. Twenty-six patients were classified as definite and the rest as probable AIH. Forty-nine patients had Type 1 AIH. Five patients had overlap syndrome. Forty-five patients (90%) received immunosuppressive therapy. Twelve of 18 patients receiving only prednisolone and 21 of 27 patients receiving prednisolone and azathioprine combination responded. Thirteen (26%) patients had therapy-related complications (infectious 5, non infectious 8) with two treatment-related deaths. CONCLUSION: Type 1 AIH was the predominant type of AIH. The majority of patients with AIH presented with chronic liver disease. There was good response to immunosuppressive therapy. Therapy-related complications occurred in one-fourth of patients.     

Possibilities of interference with the immune system of tumor bearers by non-lymphoid Fc gamma RII expressing tumor cells.

The ectopic expression of Fc gamma RII by PyV transformed 3T3 cells derived from tumors of long latency has been established. It was suggested that this expression is one of several changes conferring upon the cells an increased capacity for survival. We found that in one case cells expressing a very high level of Fc gamma RII had also a very high metastatic phenotype as compared to FcR negative cells. Direct evidence that Fc gamma RIIbl functions as a progression factor was provided by transfection experiments. The transfected gene conferred an increased malignancy and invasive phenotype upon PyV or c-Ha-ras transformed cells. In the present study we tested the possibility that Fc gamma RII expressing tumor cells could interfere with the immune system. The following subjects were investigated: 1) The ability of Fc gamma R on the tumor cells to bind the ligand and/or release IBF. 2) The effect of a local accumulation of ligand and/or IBF (assumed to take place in situ in the tumor) on Fc gamma RII expressing T cells. It was found that both tumor-derived receptor positive and beta l transfected PyV transformed cells were capable of binding aggregated mouse IgG. The binding of bivalent ligand was followed by an increase in membrane Fc gamma RII expression. Also both types of cells were capable of releasing IBF. We then tested the possibility that a local accumulation of IgG within the tumor could effect Fc gamma R expressing T cells. It was found that aggregated mouse IgG (as well as IgGl) could stimulate the proliferation of the T cell hybridoma (T2D4) and other Fc gamma RII expressing T cells. We also found that the expression of beta Fc gamma RII specific mRNA peaked at the logarithmic phase of T2D4 cultures, in parallel with their maximal potential to release IBF. Several pathways for interference with the immune system are suggested.     

Review of COVID-19 and male genital tract

COVID-19 pandemic leads to health challenges globally, and its diverse aspects need to be uncovered. Multi-organ injuries have been reported by describing potential SARS-CoV-2 entrance routes: ACE2 and TMPRSS2. Since these cell surface receptors’ expression has been disclosed within the male reproductive system, its susceptibility to being infected by SARS-CoV-2 has been summarised through this literature review. Expression of ACE2 and TMPRSS2 at RNA or protein level has been reported across various investigations indicates that the male genitalia potentially is vulnerable to SARS-CoV-2 infection. Presence of SARS-CoV-2 within semen samples and following direct viral damage, secondary inflammatory response causing orchitis or testicular discomfort and finally the amount of viral load leading testicular damage and immune response activation are among probable underlying mechanisms. Therefore, genital examination and laboratory tests should be considered to address the male reproductive tract complications and fertility issues.     

Human induced pluripotent stem cells can reach complete terminal maturation: in vivo and in vitro evidence in the erythropoietic differentiation model

Background

Human induced pluripotent stem cells offer perspectives for cell therapy and research models for diseases. We applied this approach to the normal and pathological erythroid differentiation model by establishing induced pluripotent stem cells from normal and homozygous sickle cell disease donors.

Design and Methods

We addressed the question as to whether these cells can reach complete erythroid terminal maturation notably with a complete switch from fetal to adult hemoglobin. Sickle cell disease induced pluripotent stem cells were differentiated in vitro into red blood cells and characterized for their terminal maturation in terms of hemoglobin content, oxygen transport capacity, deformability, sickling and adherence. Nucleated erythroblast populations generated from normal and pathological induced pluripotent stem cells were then injected into non-obese diabetic severe combined immunodeficiency mice to follow the in vivo hemoglobin maturation.

Results

We observed that in vitro erythroid differentiation results in predominance of fetal hemoglobin which rescues the functionality of red blood cells in the pathological model of sickle cell disease. We observed, in vivo, the switch from fetal to adult hemoglobin after infusion of nucleated erythroid precursors derived from either normal or pathological induced pluripotent stem cells into mice.

Conclusions

These results demonstrate that human induced pluripotent stem cells: i) can achieve complete terminal erythroid maturation, in vitro in terms of nucleus expulsion and in vivo in terms of hemoglobin maturation; and ii) open the way to generation of functionally corrected red blood cells from sickle cell disease induced pluripotent stem cells, without any genetic modification or drug treatment.Key words: human induced pluripotent stem cells, terminal maturation, erythropoietic differentiation     

Formation and Investigation of Physicochemical,Biological and Bacteriostatic Properties of Nanocomposite Foils Containing Silver Nanoparticles and Graphene Oxide in Hyaluronic Acid Matrix

Natural polysaccharides, including hyaluronic acid, find a wide range of applications in biomedical sciences. There is a growing interest in nanocomposites containing hyaluronic acid and nanoparticles such as nanometals or graphene. In this study, we prepared foils of pure sodium hyaluronate and sodium hyaluronate containing nanosilver, graphene oxide, nanosilver/graphene oxide and characterized their properties. UV-vis spectroscopy and scanning electron microscopy (SEM) confirmed the formation of 10–20 nm silver nanoparticles. The structural changes were investigated using Fourier transforms infrared (FTIR) spectra and size exclusion chromatography. The obtained results suggest changes in molecular weights in the samples containing nanoparticles, which was highest in a sample containing nanosilver/graphene oxide. We also assessed the mechanical properties of the foils (thickness, tensile strength and elongation at break) and their wettability. The foils containing nanosilver and nanosilver/graphene oxide presented bacteriostatic activity against E. coli, Staphylococcus spp. and Bacillus spp., which was not observed in the control and sample containing graphene oxide. The composites containing graphene oxide and nanosilver/graphene oxide exhibited a cytotoxic effect on human melanoma WM266-4 cell lines (ATCC, Manassas, VA, USA).     

Tissue engineering applications in breast cancer

Abstract

In Iran, breast cancer (BC) is the most prevalent cancer among women. The standard treatment for this cancer is partial or total removal of breast tissue, followed by chemotherapy and radiation. Tissue engineering (TE) has made new treatments for tissue loss in these patients by creating functional substitutes in the laboratory. In addition, cancer biology combined with TE provides a new strategy for evaluation of anti-BC therapy. Several innovations in TE have led to the design of scaffold or matrix based culture systems that more closely mimic the native extracellular matrix (ECM). Currently, engineered three-dimensional (3D) cultures are being developed for modelling of the tumour microenvironment. These 3D cultures fulfil the need for in vitro approaches that allow an accurate study of the molecular mechanisms and a better analysis of the drugs effect. In the present study, we review recent developments in utilising of TE in BC. Moreover, this review describes achievements of Iranian researchers in the field of breast TE.