Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. The tropism of HEV is not restricted to the liver, and the virus replicates in other organs. Not all the extrahepatic targets for HEV are identified. Herein, we found that non-decidualized primary human endometrial stromal cells (PHESCs), which are precursors for the decidua and placenta, are susceptible to HEV infection. PHESCs, isolated from healthy non-pregnant women (n = 5), were challenged with stool-derived HEV-1 and HEV-3. HEV RNA was measured by qPCR, and HEV capsid protein was assessed by flow cytometry, immunofluorescence (IF), and ELISA. HEV infection was successfully established in PHESCs. Intracellular and extracellular HEV RNA loads were increased over time, indicating efficient replication in vitro. In addition, HEV capsid protein was detected intracellularly in the HEV-infected PHESCs and accumulated extracellularly over time, confirming the viral assembly and release from the infected cells. HEV-1 replicated more efficiently in PHESCs than HEV-3 and induced more inflammatory responses. Ribavirin (RBV) treatment abolished the replication of HEV in PHESCs. In conclusion, PHESCs are permissive to HEV infection and these cells could be an endogenous source of HEV infection during pregnancy and mediate HEV vertical transmission.

HEV is the most causative agent of acute viral hepatitis globally. HEV causes acute, chronic, and extrahepatic manifestations. Chronic HEV infection develops in immunocompromised patients such as organ transplant patients, HIV-infected patients, and leukemic patients. The source of chronic HEV infection is not known. Also, the source of extrahepatic manifestations associated with HEV infection is still unclear. Hepatotropic viruses such as HCV and HBV replicate in peripheral blood mononuclear cells (PBMCs) and these cells become a source of chronic reactivation of the infections in allograft organ transplant patients. Herein, we reported that PBMCs and bone marrow-derived macrophages (BMDMs), isolated from healthy donors (n = 3), are susceptible to HEV in vitro. Human monocytes (HMOs), human macrophages (HMACs), and human BMDMs were challenged with HEV-1 and HEV-3 viruses. HEV RNA was measured by qPCR, the marker of the intermediate replicative form (ds-RNA) was assessed by immunofluorescence, and HEV capsid protein was assessed by flow cytometry and ELISA. HEV infection was successfully established in primary HMOs, HMACs, and human BMDMs, but not in the corresponding cells of murine origin. Intermediate replicative form (ds RNA) was detected in HMOs and HMACs challenged with HEV. The HEV load was increased over time, and the HEV capsid protein was detected intracellularly in the HEV-infected cells and accumulated extracellularly over time, confirming that HEV completes the life cycle inside these cells. The HEV particles produced from the infected BMDMs were infectious to naive HMOs in vitro. The HEV viral load was comparable in HEV-1- and HEV-3-infected cells, but HEV-1 induced more inflammatory responses. In conclusion, HMOs, HMACs, and human BMDMs are permissive to HEV infection and these cells could be the source of chronic and recurrent infection, especially in immunocompromised patients. Replication of HEV in human BMDMs could be related to hematological disorders associated with extrahepatic manifestations.

Renal disorders are associated with Hepatitis E virus (HEV) infection. Progression to end-stage renal disease and acute kidney injury are complications associated with HEV infection. The mechanisms by which HEV mediates the glomerular diseases remain unclear. CD10⁺/CD13⁺ primary proximal tubular (PT) epithelial cells, isolated from healthy donors, were infected with HEV. Inflammatory markers and kidney injury markers were assessed in the presence or absence of peripheral blood mononuclear cells (PBMCs) isolated from the same donors. HEV replicated efficiently in the PT cells as shown by the increase in HEV load over time and the expression of capsid Ag. In the absence of PBMCs, HEV was not nephrotoxic, with no direct effect on the transcription of chemokines (Cxcl-9, Cxcl-10, and Cxcl-11) nor the kidney injury markers (kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and interleukin 18 (lL-18)). While higher inflammatory responses, upregulation of chemokines and kidney injury markers expression, and signs of nephrotoxicity were recorded in HEV-infected PT cells cocultured with PBMCs. Interestingly, a significantly higher level of IFN-γ was released in the PBMCs-PT coculture compared to PT alone during HEV infection. In conclusion: The crosstalk between immune cells and renal epithelium and the signal axes IFN-γ/chemokines and IL-18 could be the immune-mediated mechanisms of HEV-induced renal disorder.

Breast cancer is one of the most malignant tumors in women across the globe. Diagnosis of breast cancer at early stages is essential to improve treatment outcomes and decrease mortality rates. There is a pressing need for new non-invasive biomarkers to improve early diagnosis of breast cancer. This study aims to assess plasma miR-27a for the early diagnosis of breast cancer. miR-27a was evaluated in a total of 95 blood samples, 40 newly diagnosed cancer patients, 20 patients with benign breast lesions, 20 females with positive family history for breast cancer and 15 apparently healthy controls, using quantitative real time polymerase chain reaction. Our results exhibited significantly higher expression level of plasma miR-27a in breast cancer patients (median= 8.3 and 19 fold change for early and late stages respectively) compared to controls, high risk group and benign group with (P <0.001) for each. Plasma miR-27a was significantly higher in late breast cancer (median=19 fold change) compared to early breast cancer (median= 8.3) with (P <0.001). There was no statistically significant difference of plasmamiR-27a levels in benign group (median=1.8 fold change) compared to both control group and high risk group. There was no statistically significant difference of plasma miR-27a levels in high risk group (median= 1.2 fold change) compared to control group (median= 1 fold change). We performed Receiver Operating Characteristic (ROC) analysis for discriminating malignant from non-malignant cases. Plasma miR-27a yielded an area under the curve (AUC) of 0.983 with sensitivity 97.5%, specificity 91% and accuracy 94%.We concluded that miR-27a expression level represents sensitive and specific non-invasive molecular biomarkers for diagnosis of breast cancer.

Background: Bariatric surgery is an effective treatment that induces substantial and sustained weight loss through restriction, malabsorption, and hormonal mechanisms that regulate appetite and energy balance. This study aimed to assess the role of body contouring surgery in enhancing long-term weight loss maintenance and improving metabolic outcomes following bariatric surgery. Methods: This prospective comparative study was conducted at Assiut University Hospitals on 60 postbariatric (sleeve) patients aged 20 to 60 years who underwent body contouring surgery and had been stable within 5 kg for 3 months. Patients were divided into 2 equal groups. Group A: underwent postbariatric body contouring. Group B: served as the control group and did not undergo body contouring surgery. Results: Group A showed significantly greater reductions in weight at 3 months ( ) and 6 months ( ), and in body mass index at 3 months and 6 months ( ) than group B. A significantly lower basal metabolic rate was observed in group A at 6 months ( ), with a significant decline from baseline ( ). While hematological, coagulation, and B-type natriuretic peptide parameters remained comparable between groups, group A demonstrated significantly better metabolic and inflammatory outcomes, including lower total cholesterol, triglycerides, low-density lipoprotein cholesterol, tumor necrosis factor-alpha, and high-sensitivity C-reactive protein levels ( ), and higher high-density lipoprotein cholesterol levels at 3 months and 6 months ( ). Furthermore, most patients reported high satisfaction with body contouring surgery. Conclusions: Postbariatric body contouring surgery appears to be a safe and effective adjunct to bariatric surgery, contributing to sustained weight loss and improved metabolic outcomes.