Background:

MicroRNA-155 (miR-155) is a pro-inflammatory molecule implicated in autoimmune and inflammatory diseases, including inflammatory bowel disease (IBD). This study evaluated circulating miR-155 expression in IBD patients versus healthy controls and its association with clinical markers.

Methods:

Thirty IBD patients (20 ulcerative colitis [UC], 10 Crohn’s disease [CD]) and 20 age- and sex-matched healthy controls were enrolled. Plasma miR-155 levels were measured using qRT-PCR. Clinical data included C-reactive protein (CRP), fecal calprotectin, and Mayo score (for UC). Analyses were conducted using SPSS v26.0.

Results:

miR-155 expression was significantly elevated in IBD patients (median fold change: UC = 24.2, CD = 37.5, controls = 1.00; p < 0.0001). No significant difference was observed between UC and CD groups. miR-155 positively correlated with fecal calprotectin (ρ = 0.475, p = 0.008) and Mayo score in UC patients (ρ = 0.748, p < 0.001).

Conclusion:

Circulating miR-155 is significantly overexpressed in IBD and correlates with intestinal inflammation and disease activity, supporting its utility as a non-invasive biomarker.

Inflammatory bowel disease (IBD) is a persistent inflammatory illness of the gastrointestinal tract (GIT) triggered by an inappropriate immune response to environmental stimuli in genetically predisposed persons. Unfortunately, IBD patients' quality of life is negatively impacted by the symptoms associated with the disease. The exact etiology of IBD pathogenesis is not fully understood, but the emerging research indicated that the microRNA (miRNA) plays an important role. miRNAs have been documented to possess a significant role in regulating pro- and anti-inflammatory pathways, in addition to their roles in several physiological processes, including cell growth, proliferation, and apoptosis. Variations in the miRNA profiles might be a helpful prognostic indicator and a valuable tool in the differential diagnosis of IBD. Most interestingly, these miRNAs have a promising therapeutic target in several pre-clinical animal studies and phase 2 clinical studies to alleviate inflammation and improve patient's quality of life. This comprehensive review discusses the current knowledge about the significant physiological role of different miRNAs in the health of the intestinal immune system and addresses the role of the most relevant differentially expressed miRNAs in IBD, identify their potential targets, and emphasize their diagnostic and therapeutic potential for future research.

Introduction: CD34+CD38-stem cells were identified as the most related markers to acute myeloid leukemia (AML) progression, resistance, and relapse. However, there is still a lack of published data identifying the level of CD34 and CD38 during induction chemotherapy and after complete remission. Objectives: This study aimed to evaluate the levels of CD34+CD38+progenitor cells and CD34+CD38-stem cells in AML patients at diagnosis and after induction chemotherapy. Patients and Methods: This is a prospective cohort study. Both CD34 and CD38 cell markers were identified using f low cytometry in newly diagnosed AML patients and after induction chemotherapy. Results: Forty newly diagnosed AML patients (27 males and 13 females) were followed up after induction chemotherapy. Results revealed a statistically significant decline (P ≤ 0.05) in CD34+CD38-stem cell levels as well as in CD34+CD38+progenitor cell levels in AML patients who achieved complete or incomplete remission compared to newly diagnosed AML patients. Besides, age and CD34+CD38-stem cells exhibited a statistically significant positive correlation at diagnosis. Conclusion: Our study showed CD34+CD38-stem cells are associated with disease progression and poor survival in AML patients. We concluded that, CD34 and CD38 are promising follow-up markers for AML patients on induction chemotherapy. In order to keep AML patients in full remission and increase their chances of survival, medications that target leukemic stem cells (LSCs) should be used in conjunction with the usual chemotherapy that targets blasts.

Background Acute myeloid leukemia (AML) has been linked to immunological disorders. The immunological milieu associated with AML is still debated, particularly regarding interleukins (IL) linked to T regulatory cells dysregulation and apoptosis. Till now, IL33 has not been studied in AML patients on induction chemotherapy or correlated with AML immunophenotypic markers. This study aimed to investigate the levels of IL10, IL33, and IL35 as possible follow-up markers in AML patients at diagnosis and after chemotherapy induction and to correlate their levels with AML immunophenotypic markers. Patients and methods In this study, newly diagnosed AML patients were followed up from diagnosis till complete remission or death, and levels of IL10, IL33, and IL35 were detected using enzyme-linked immunosorbent assay. Results The results revealed that IL10 and IL35 levels were significantly elevated in newly diagnosed AML patients in comparison to the control group (P>0.001). After chemotherapy induction, IL10 and IL35 levels in complete remission in AML patients were significantly reduced (P>0.001). The results of this study reveal, for the first time, a statistically significant association between IL33 level and CD13 prognostic marker.

Impaired renal functions have been reported with Hepatitis E virus (HEV) infections, especially with genotypes 3 and 4. These complications were reported during the acute and chronic phases of infection. HEV genotype 1 causes acute infection, and the effect of HEV-1 infections on renal functions is not known. We examined the kidney function parameters in the serum of HEV-1 patients (AHE, n = 31) during the acute phase of infection. All of the included patients developed an acute self-limiting course of infection, without progression to fulminant hepatic failure. We compared the demographic, laboratory, and clinical data between AHE patients with normal kidney function parameters and those with abnormal renal parameters. Out of 31 AHE patients, 5 (16%) had abnormal kidney function tests (KFTs) during the acute phase of infection. Three patients had abnormal serum urea and creatinine, and two patients had either abnormal urea or creatinine. Four out of five patients had an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2. AHE patients with abnormal KFTs were older and had a lower level of albumin, but a slightly elevated alanine transaminase (ALT) compared to AHE patients with normal KFTs. There were no significant differences between the two groups in terms of age, sex, liver transaminase levels, and the viral load. Similarly, the clinical presentations were comparable in both groups. Interestingly, these KFTs in patients with abnormal renal parameters returned to normal levels at the recovery. The serum creatinine level was not correlated with patients’ age or liver transaminase levels, but it was significantly negatively correlated with albumin level. In conclusion, this study is the first report that evaluated KFTs in patients during the acute phase of HEV-1 infections. Impaired KFTs in some AHEpatients resolved at convalescence. KFTs and renal complications should be monitored during HEV-1 infections.

The World Health Organization (WHO) recently alerted the emergence of new pathogens causing acute hepatitis in children across several countries. This new situation directs us to the screening of neglected pathogens that cause acute hepatitis. Q-fever is a zoonotic disease, caused by Coxiella burnetii. Although a high seroprevalence of Coxiella burnetii was recorded in animals present in Egypt, Q-fever is still a neglected disease, and the diagnosis of Q-fever is not routinely performed in Egyptian hospitals. In this study, we performed a retrospective assessment for Coxiella burnetii in cases of hepatitis of unknown causes (HUC) enrolled in Assiut University hospitals, in Egypt. Out of 64 samples of HUC, 54 samples were negative for all hepatitis markers, labeled as acute hepatitis of unknown etiology (AHUE), and 10 samples tested positive for adenovirus and Hepatitis E virus (HEV). Q-fever was detected in 3 out of 54 (5.6%) of AHUE, and one sample was confirmed as coinfection of HEV/Q-fever. Jaundice was the most common clinical symptom developed in the patients. In conclusion, Coxiella burnetii was found to be a potential cause of acute hepatitis in HUC. The diagnosis of Q-fever should be considered in acute hepatitis cases in Egyptian hospitals.

HEV-Ag ELISA assay is a reliable diagnostic test in resource-limited areas. HEV genotype 1 (HEV-1) infections are either self-limited or progress to fulminant hepatic failure (FHF) and death if anti- HEV therapy is delayed. Limited data is available about the diagnostic utility of HEV Ag on HEV-1 infections. Herein we aimed to study the kinetics of HEV Ag during HEV-1 infections at different stages, i.e., acute HEV infection, recovery, and progression to FHF. Also, we evaluated the diagnostic utility of this marker to predict the outcomes of HEV-1 infections. Plasma of acute hepatitis E (AHE) patients were assessed for HEV RNA by RT-qPCR, HEV Ag, and anti-HEV IgM by ELISA. The kinetics of HEV Ag was monitored at different time points; acute phase of infection, recovery, FHF stage, and post-recovery. Our results showed that the level of HEV Ag was elevated in AHE patients with a significantly higher level in FHF patients than recovered patients. We identified a plasma HEV Ag threshold that can differentiate between self-limiting infection and FHF progression with 100% sensitivity and 88.89% specificity. HEV Ag and HEV RNA have similar kinetics during the acute phase and self-limiting infection. In the FHF stage, HEV Ag and anti-HEV IgM have similar patterns of kinetics which could be the cause of liver damage. In conclusion, the HEV Ag assay can be used as a biomarker for predicting the consequences of HEV-1 infections which could be diagnostically useful for taking the appropriate measures to reduce the complica tions, especially for high-risk groups.

A novel series of 2-substituted thio-7-chloroquinazolin-4(3H)-one derivatives was rationally designed, synthesized, and evaluated as dual inhibitors of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor-2 (VEGFR-2) with potential anticancer activity. Structural optimization was achieved through the incorporation of diverse linkers and pharmacophoric motifs, including aryl amides, hydrazones, chalcones, and heterocyclic moieties, to target key kinase binding domains. In vitro screening against the NCI-60 human tumor cell line panel revealed several compounds with broad-spectrum antiproliferative activity, among which the chalcone derivative (11a) emerged as the most potent. Compound (11a) exhibited low micromolar GI₅₀ values, high selectivity towards cancer cells over normal cells, and strong dual inhibition of EGFR and VEGFR-2 in the nanomolar range. Mechanistic studies demonstrated that (11a) induced G₁/S phase cell cycle arrest, activated apoptotic pathways, suppressed receptor phosphorylation, and promoted PARP-1 cleavage. Notably, (11a) retained inhibitory activity against clinically relevant EGFR resistance mutants, including C797S. Molecular docking and dynamics simulations indicated stable, favorable binding within the ATP-binding sites of both kinases. Collectively, these findings identify compound (11a) as a promising dual-target anticancer lead warranting further preclinical investigation.