Biology subjects

Kassem, K. F.

Publications and source records attributed to Kassem, K. F..

2 recordsLinked to original sources

bioRxiv2026

Experimental Evidence for HIV-Associated Phenotypic Reprogramming of CD4⁺ T Cells: An Exploratory Immunological Study

BackgroundHuman immunodeficiency virus type 1 (HIV-1) infection is characterized by progressive immune dysfunction, classically attributed to depletion of CD4{square} T lymphocytes. Despite decades of research, the mechanisms underlying the functional deterioration of cellular immunity remain incompletely understood. We hypothesized that, in addition to quantitative CD4{square} T-cell loss, HIV infection may induce phenotypic reprogramming of CD4{square} T cells, resulting in altered surface-marker expression and impaired immunological function. MethodsPeripheral blood samples were obtained from untreated HIV-positive individuals and healthy controls. Flow cytometric immunophenotyping, recombinant HIV-1 p17 stimulation assays, immunofluorescence imaging, ELISPOT analysis of interferon-{gamma} secretion, and CD4{square}/CD8{square}conjugation assays were performed to investigate dynamic changes in T-cell phenotype and function following viral protein exposure. ResultsHIV-positive samples demonstrated progressive reductions in CD4{square} T-cell counts accompanied by corresponding increases in CD8{square} T-cell populations following p17 stimulation, while the combined CD4{square}/CD8{square} T-cell count remained relatively stable. Immunofluorescence analyses identified cells exhibiting simultaneous CD4- and CD8-associated marker expression after prolonged incubation. Functional analyses further demonstrated markedly reduced interferon-{gamma} secretion in the newly identified cell population compared with conventional CD8{square} T cells. Conjugation assays additionally suggested altered cellular interaction patterns between reprogrammed cells and target CD4{square}lymphocytes. ConclusionsThese findings support the hypothesis that chronic HIV infection may be associated with phenotypic reprogramming of CD4{square} T cells rather than simple quantitative depletion alone. Although the underlying molecular mechanisms remain to be established, this exploratory model provides an alternative framework for investigating HIV-associated immune dysfunction and may stimulate future studies using lineage-tracing, single-cell transcriptomics, and epigenetic profiling to evaluate this proposed mechanism.

immunology↗

bioRxiv2026

GLX10, a Novel Immunometabolic Modulator, Enhances Glycemic Control and Suppresses Inflammatory Signaling in a High-Fat Diet and Streptozotocin-Induced Rat Model of Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder characterized by persistent hyperglycemia, insulin resistance, and chronic low-grade inflammation. Despite the widespread use of established therapies such as metformin, long-term glycemic control remains suboptimal, and disease progression is often not adequately prevented. This highlights the need for novel therapeutic strategies that address both metabolic dysfunction and the underlying immunometabolic components of the disease. In this study, GLX10 (GLXM100) was evaluated as a novel immune modulator in a high-fat diet (HFD) and low-dose streptozotocin (STZ)-induced rat model of T2DM over a 91-day period. Glycemic outcomes were assessed using terminal random blood glucose and oral glucose tolerance testing (OGTT), with glucose exposure quantified by area under the curve (AUC 0-120). Complementary in vitro investigations were performed in hepatic and macrophage cell models to assess cytocompatibility, nitric oxide production, and modulation of pro-inflammatory cytokines, including IL-6 and TNF-. GLX10 treatment resulted in a significant reduction in random blood glucose levels and a marked improvement in glucose tolerance compared to diabetic control animals. Importantly, GLX10 demonstrated greater improvement in OGTT AUC compared to metformin under the same experimental conditions, indicating enhanced dynamic glucose regulation. In vitro, GLX10 maintained viability in normal hepatic cells while significantly suppressing nitric oxide production and inflammatory cytokine outputs in macrophages, supporting a favorable safety and immune profile. Collectively, these findings demonstrate that GLX10 exerts robust antidiabetic activity through a dual mechanism involving metabolic regulation and suppression of inflammatory signaling. The integration of in vivo efficacy with supportive in vitro safety and mechanistic data provides a strong preclinical foundation and supports the further development of GLX10 as a promising therapeutic candidate for T2DM.

immunology↗