Resazurin dye is an in vivo sensor of kidney tubular function.

Glomerular filtration rate (GFR) is the main functional index of kidney health and disease. Currently, no methods are available to directly measure tubular mass and function. Here, we report a serendipitous finding that the in vitro cell viability dye resazurin can be used in mice as an exogenous sensor of tubular function.

Partial repair causes permanent defects in papillary structure and function after reversal of urinary obstruction.

Unlabelled: Urinary obstruction causes injury to the renal papilla and leads to defects in the ability to concentrate urine which predisposes to progressive kidney injury. However, the regenerative capacity of the papilla after reversal of obstruction is poorly understood. To address this, we developed a mouse model of reversible urinary obstruction which is characterized by extensive papillary injury, followed by a robust regeneration response and complete histological recovery over a 3- month period.

Role of the CDKL1-SOX11 signaling axis in acute kidney injury.

The biology of the cyclin-dependent kinase-like (CDKL) kinase family remains enigmatic. Contrary to their nomenclature, CDKLs do not rely on cyclins for activation and are not involved in cell cycle regulation. Instead, they share structural similarities with mitogen-activated protein kinases and glycogen synthase kinase-3, although their specific functions and associated signaling pathways are still unknown.

A genetically inducible endothelial niche enables vascularization of human kidney organoids with multilineage maturation and emergence of renin expressing cells.

Vascularization plays a critical role in organ maturation and cell-type development. Drug discovery, organ mimicry, and ultimately transplantation hinge on achieving robust vascularization of in vitro engineered organs. Here, focusing on human kidney organoids, we overcame this hurdle by combining a human induced pluripotent stem cell (iPSC) line containing an inducible ETS translocation variant 2 (ETV2) (a transcription factor playing a role in endothelial cell development) that directs endothelial differentiation in vitro, with a non-transgenic iPSC line in suspension organoid culture.

Inhibition of retinoic acid signaling in proximal tubular epithelial cells protects against acute kidney injury.

Retinoic acid receptor (RAR) signaling is essential for mammalian kidney development but, in the adult kidney, is restricted to occasional collecting duct epithelial cells. We now show that there is widespread reactivation of RAR signaling in proximal tubular epithelial cells (PTECs) in human sepsis-associated acute kidney injury (AKI) and in mouse models of AKI. Genetic inhibition of RAR signaling in PTECs protected against experimental AKI but was unexpectedly associated with increased expression of the PTEC injury marker Kim1.

Functional characterization of ion channels expressed in kidney organoids derived from human induced pluripotent stem cells.

Kidney organoids derived from human or rodent pluripotent stem cells have glomerular structures and differentiated/polarized nephron segments. Although there is an increasing understanding of the patterns of expression of transcripts and proteins within kidney organoids, there is a paucity of data regarding functional protein expression, in particular on transporters that mediate the vectorial transport of solutes. Using cells derived from kidney organoids, we examined the functional expression of key ion channels that are expressed in distal nephron segments: the large-conductance Ca-activated K (BK) channel, the renal outer medullary K (ROMK, Kir1.

Modeling oxidative injury response in human kidney organoids.

Background: Hemolysis occurs in many injury settings and can trigger disease processes. In the kidney, extracellular hemoglobin can induce damage via several mechanisms. These include oxidative stress, mitochondrial dysfunction, and inflammation, which promote fibrosis and chronic kidney disease.

HMP-S7 Is a Novel Anti-Leukemic Peptide Discovered from Human Milk.

Chemotherapy in childhood leukemia is associated with late morbidity in leukemic survivors, while certain patient subsets are relatively resistant to standard chemotherapy. It is therefore important to identify new agents with sensitivity and selectivity towards leukemic cells, while having less systemic toxicity. Peptide-based therapeutics has gained a great deal of attention during the last few years.

Cell-Main Spectra Profile Screening Technique in Simulation of Circulating Tumour Cells Using MALDI-TOF Mass Spectrometry.

Circulating atypical cells (CAC) are released from a primary tumour site into peripheral blood and are indicators of cancer metastasis. CAC occur at very low frequency in circulating blood, and their detection remains challenging. Moreover, white blood cells (WBC) are the major contaminant in enriched CAC samples.

Production and characterization of haploidentical CD19 CAR T cells: Validated to induce a continuous complete remission in a patient with relapsed refractory B-cell ALL.

Aims: The purpose of this study was to design and manufacture CD19 chimeric antigen receptor (CAR)-modified T cells for clinical use in Thailand, as a model for how this technology can be directly applied at individual institutions treating high-risk leukemia patients.

Methods: We constructed second-generation CAR T cells expressing CD19 scFV-CD28-CD3ζ with different lengths of the spacer region: full, intermediate, and short length, by using a lentiviral vector. We wanted to determine whether the difference in length of the spacer would affect the cytotoxic potential of the CD19 CAR T cells against the leukemic cells.

Evaluation of cisplatin-induced injury in human kidney organoids.

Acute kidney injury (AKI) remains a major global healthcare problem, and there is a need to develop human-based models to study AKI in vitro. Toward this goal, we have characterized induced pluripotent stem cell-derived human kidney organoids and their response to cisplatin, a chemotherapeutic drug that induces AKI and preferentially damages the proximal tubule. We found that a single treatment with 50 µM cisplatin induces hepatitis A virus cellular receptor 1 () and C-X-C motif chemokine ligand 8 () expression, DNA damage (γH2AX), and cell death in the organoids but greatly impairs organoid viability.

Suppressive Characteristics of Umbilical Cord Blood-derived Regulatory T Cells After Ex Vivo Expansion on Autologous and Allogeneic T Effectors and Various Lymphoblastic Cells.

The third-party umbilical cord blood (UCB)-derived regulatory T cells (Treg) are an alternative to donor-derived Treg as cellular therapy of graft-versus-host disease following hematopoietic stem cell transplantation. However, their suppressive characteristics against autologous and allogeneic T effector cells (Teff) have rarely been documented. The exact role of UCB-Treg in hematologic malignancies is also uncertain.

Secretory High-Mobility Group Box 1 Protein Affects Regulatory T Cell Differentiation in Neuroblastoma Microenvironment .

Neuroblastoma (NB) is the most common extracranial tumor of childhood with poor prognosis in a high-risk group. An obstacle in the development of treatment for solid tumors is the immunosuppressive nature of the tumor microenvironment (TME). Regulatory T cells (Tregs) represent a T cell subset with specialized function in immune suppression and maintaining self-tolerance.

Immune Escape Mechanisms and Future Prospects for Immunotherapy in Neuroblastoma.

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood with 5-year survival rate of 40% in high-risk patients despite intensive therapies. Recently, adoptive cell therapy, particularly chimeric antigen receptor (CAR) T cell therapy, represents a revolutionary treatment for hematological malignancies. However, there are challenges for this therapeutic strategy with solid tumors, as a result of the immunosuppressive nature of the tumor microenvironment (TME).

Hypoxia enhances cholangiocarcinoma invasion through activation of hepatocyte growth factor receptor and the extracellular signal‑regulated kinase signaling pathway.

Hypoxia is associated with tumor progression and poor prognosis in several cancer types. The present study aimed to examine the contribution of hypoxia (1% O2) to cancer progression in a cholangiocarcinoma cell line, RMCCA‑1. The molecular basis of the hypoxic response pathway was investigated.