Ecological and human health risk from exposure to metal contaminated sediments in a subtropical river affected by anthropogenic activities: A case study from river Yamuna.

Heavy metal enrichment in river sediments poses a significant risk to human and aquatic health. The Yamuna River faces severe challenges due to untreated industrial and domestic wastewater discharge. The study evaluates sediment metal content, ecological and human health risks, and potential sources.

Structure-guided engineering of immunotherapies targeting TRBC1 and TRBC2 in T cell malignancies.

Peripheral T cell lymphomas are typically aggressive with a poor prognosis. Unlike other hematologic malignancies, the lack of target antigens to discriminate healthy from malignant cells limits the efficacy of immunotherapeutic approaches. The T cell receptor expresses one of two highly homologous chains [T cell receptor β-chain constant (TRBC) domains 1 and 2] in a mutually exclusive manner, making it a promising target.

Enhancing CAR T-cell Therapy Using Fab-Based Constitutively Heterodimeric Cytokine Receptors.

Adoptive T-cell therapy aims to achieve lasting tumor clearance, requiring enhanced engraftment and survival of the immune cells. Cytokines are paramount modulators of T-cell survival and proliferation. Cytokine receptors signal via ligand-induced dimerization, and this principle has been hijacked utilizing nonnative dimerization domains.

Exploration of T cell immune responses by expression of a dominant-negative SHP1 and SHP2.

SHP1 and SHP2 are SH2 domain-containing proteins which have inhibitory phosphatase activity when recruited to phosphorylated ITIMs and ITSMs on inhibitory immune receptors. Consequently, SHP1 and SHP2 are key proteins in the transmission of inhibitory signals within T cells, constituting an important point of convergence for diverse inhibitory receptors. Therefore, SHP1 and SHP2 inhibition may represent a strategy for preventing immunosuppression of T cells mediated by cancers hence improving immunotherapies directed against these malignancies.

Dual targeting of CD19 and CD22 against B-ALL using a novel high-sensitivity aCD22 CAR.

CAR T cells recognizing CD19 effectively treat relapsed and refractory B-ALL and DLBCL. However, CD19 loss is a frequent cause of relapse. Simultaneously targeting a second antigen, CD22, may decrease antigen escape, but is challenging: its density is approximately 10-fold less than CD19, and its large structure may hamper immune synapse formation.

Efficient clinical-grade γ-retroviral vector purification by high-speed centrifugation for CAR T cell manufacturing.

γ-Retroviral vectors (γ-RV) are powerful tools for gene therapy applications. Current clinical vectors are produced from stable producer cell lines which require minimal further downstream processing, while purification schemes for γ-RV produced by transient transfection have not been thoroughly investigated. We aimed to develop a method to purify transiently produced γ-RV for early clinical studies.

Reconstruction of Scalp with Local Axial Flaps.

The scalp is a unique part of the human body and various etiological factors, such as tumour extirpation, infection, burns, or trauma, can lead to scalp defects. Primary closure, skin grafting, local flaps, tissue expansion or free tissue transfer are modalities available for scalp reconstruction. In this article, the authors share their institutional experience using various local flaps concerning the size, location, depth of defect and the quality of surrounding tissue.

CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial.

Chimeric antigen receptor (CAR) T cells targeting CD19 or CD22 have shown remarkable activity in B cell acute lymphoblastic leukemia (B-ALL). The major cause of treatment failure is antigen downregulation or loss. Dual antigen targeting could potentially prevent this, but the clinical safety and efficacy of CAR T cells targeting both CD19 and CD22 remain unclear.

Comparison of the outcomes of adipofascial and two-staged fasciocutaneous reverse sural flap in patients with lower leg trauma.

Background: Distal one - third trauma of the lower limb is a complex condition to treat. The reverse sural flap is a time tested procedure for reconstruction of such defects especially in patients where free flaps are ruled out due to comorbidities. The purpose of this study is to compare the two modifications of the classical technique of reverse sural flap (adipofascial and fasciocutaneous) which is lacking in the literature.

Enhancement of the immunoregulatory potency of mesenchymal stromal cells by treatment with immunosuppressive drugs.

Background Aims: Multipotent mesenchymal stromal cells (MSCs) are distinguished by their ability to differentiate into a number of stromal derivatives of interest for regenerative medicine, but they also have immunoregulatory properties that are being tested in a number of clinical settings.

Methods: We show that brief incubations with rapamycin, everolimus, FK506 or cyclosporine A increase the immunosuppressive potency of MSCs and other cell types.

Results: The treated MSCs are up to 5-fold more potent at inhibiting the induced proliferation of T lymphocytes in vitro.