Differentiation of Uc-MSCs into insulin secreting islet-like clusters by trypsin through TGF-beta signaling pathway.

Differentiation of human umbilical cord mesenchymal stem cells (Uc-MSCs) into islet-like clusters which are capable of synthesizing and secreting insulin can potentially serve as donors for islet transplantation in the patient deficiency in islet β cell function both in type 1 or type 2 diabetic patients. Therefore, we developed an easy and higher efficacy approach by trypsinazing the Uc-MSCs and followed culture in differentiation medium to induce of Uc-MSCs differentiation into islet-like clusters, and the potential mechanism that in the early stage of differentiation was also investigated by using RNA-sequencing and bioinformatics. Results show that induction efficacy was reached to 98% and TGF-β signaling pathway may play critical role in the early stage differentiation, it was further confirmed that the retardant effect of differentiation progress either in cell morphology or in islet specific genes expression can be observed upon blocking the activation of TGF-β signaling pathway using specific inhibitor of LY2109761 (TβRI/II kinase inhibitor).

Trioxidized cysteine in the aging proteome mimics the structural dynamics and interactome of phosphorylated serine.

Aging is the primary risk factor for the development of numerous human chronic diseases. On a molecular level, it significantly impacts the regulation of protein modifications, leading to the accumulation of degenerative protein modifications (DPMs) such as aberrant serine phosphorylation (p-Ser) and trioxidized cysteine (t-Cys) within the proteome. The altered p-Ser is linked to abnormal cell signaling, while the accumulation of t-Cys is associated with chronic diseases induced by oxidative stress.

The Prognostic Value of CD39 as a Marker of Tumor-Specific T Cells in Triple-Negative Breast Cancer in Asian Women.

Triple-negative breast cancer (TNBC) has a poor prognosis with limited therapeutic options available for affected patients. Efforts are ongoing to identify surrogate markers for tumor-specific CD8 T cells that can predict the response to immune checkpoint inhibitor (ICI) therapies, such as programmed cell death protein 1 or programmed cell death ligand-1 blockade. We have previously identified tumor-specific CD39CD8 T cells in non-small cell lung cancer that might help predict patient responses to programmed cell death protein 1 or programmed cell death ligand-1 blockade.

JAK2 as a surface marker for enrichment of human pluripotent stem cells-derived ventricular cardiomyocytes.

Background: Human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) hold great promise for cardiac disease modelling, drug discovery and regenerative medicine. Despite the advancement in various differentiation protocols, the heterogeneity of the generated population composed of diverse cardiac subtypes poses a significant challenge to their practical applications. Mixed populations of cardiac subtypes can compromise disease modelling and drug discovery, while transplanting them may lead to undesired arrhythmias as they may not integrate and synchronize with the host tissue's contractility.

3D Printed Bioactive PLGA Dermal Scaffold for Burn Wound Treatment.

Burn injury represents a major global public healthcare problem and has a significant health-economics impact. In this study, we report on a 3D printed poly(lactic--glycolic acid) (PLGA) dermal scaffold containing bioactive PLGA for burn wound healing. Bioactive brush copolymers containing pendant side chains of PLGA and PEGylated Arg-Gly-Asp tripeptide (RGD) or hyaluronic acid (HA) were synthesized by ring-opening metathesis polymerization (ROMP).

Up-regulation of SLC7A11/xCT creates a vulnerability to selenocystine-induced cytotoxicity.

The SLC7A11/xCT cystine and glutamate antiporter has emerged as an attractive target for cancer therapy due to its selective overexpression in multiple cancers and its role in preventing ferroptosis. Utilizing pharmacological and genetic approaches in hepatocellular carcinoma cell lines, we demonstrate that overexpression of SLC7A11 engenders hypersensitivity towards l-selenocystine, a naturally occurring diselenide that bears close structural similarity to l-cystine. We find that the abundance of SLC7A11 positively correlates with sensitivity to l-selenocystine, but surprisingly, not to Erastin, an inhibitor of SLC7A11 activity.

Expression and engineering of PET-degrading enzymes from , and .

Mismanagement of PET plastic waste significantly threatens human and environmental health. Together with the relentless increase in plastic production, plastic pollution is an issue of rising concern. In response to this challenge, scientists are investigating eco-friendly approaches, such as bioprocessing and microbial factories, to sustainably manage the growing quantity of plastic waste in our ecosystem.

Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy.

Loss of pancreatic beta cells is the central feature of all forms of diabetes. Current therapies fail to halt the declined beta cell mass. Thus, strategies to preserve beta cells are imperatively needed.

Direct arene trifluoromethylation enabled by promiscuous activity of fungal laccase.

Laccase from was found to oxidize non-phenolic arenes and enable the trifluoromethylation of arenes in the presence of generated CF radicals at a catalyst loading as low as 0.0034%. The biocatalytic trifluoromethylation proceeded under mild conditions and could increase the yield by up to 12 fold, compared to the control.

Complete remission of tumors in mice with neoantigen-painted exosomes and anti-PD-1 therapy.

Neoantigen-based cancer vaccines are emerging as promising tumor therapies, but enhancement of immunogenicity can further improve therapeutic outcomes. Here, we demonstrate that anchoring different peptide neoantigens on subcutaneously administered serum exosomes promote lymph node homing and dendritic cell uptake, resulting in significantly enhanced antigenicity in vitro and in vivo. Exosomes anchoring of melanoma peptide neoantigens augmented the magnitude and breadth of T cell response in vitro and in vivo, to a greater extent with CD8 T cell responses.

iPS-cell-derived microglia promote brain organoid maturation via cholesterol transfer.

Microglia are specialized brain-resident macrophages that arise from primitive macrophages colonizing the embryonic brain. Microglia contribute to multiple aspects of brain development, but their precise roles in the early human brain remain poorly understood owing to limited access to relevant tissues. The generation of brain organoids from human induced pluripotent stem cells recapitulates some key features of human embryonic brain development.

Therapeutic Efficacy of Mesenchymal Stem/Stromal Cell Small Extracellular Vesicles in Alleviating Arthritic Progression by Restoring Macrophage Balance.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and damage, often associated with an imbalance in M1/M2 macrophages. Elevated levels of anti-inflammatory M2 macrophages have been linked to a therapeutic response in RA. We have previously demonstrated that mesenchymal stem/stromal cell small extracellular vesicles (MSC-sEVs) promote M2 polarization and hypothesized that MSC-sEVs could alleviate RA severity with a concomitant increase in M2 polarization.

Serrated colorectal cancer: preclinical models and molecular pathways.

Serrated lesions are histologically heterogeneous, and detection can be challenging as these lesions have subtle features that may be missed by endoscopy. Furthermore, while approximately 30% of colorectal cancers (CRCs) arise from serrated lesions, only 8-10% of invasive serrated CRCs exhibit serrated morphology at presentation, suggesting potential loss of apparent characteristics with increased malignancy. Thus, understanding the genetic basis driving serrated CRC initiation and progression is critical to improve diagnosis and identify therapeutic biomarkers and targets to guide disease management.

wnt10a is required for zebrafish median fin fold maintenance and adult unpaired fin metamorphosis.

Background: Mutations of human WNT10A are associated with odonto-ectodermal dysplasia syndromes. Here, we present analyses of wnt10a loss-of-function mutants in the zebrafish.

Results: wnt10a mutant zebrafish embryos display impaired tooth development and a collapsing median fin fold (MFF).

To B(enign) or Not to B: functionalisation of variant in a mild form of argininosuccinate lyase deficiency identified through newborn screening.

Argininosuccinate lyase (ASL) deficiency is an autosomal recessive disorder of the urea cycle with a diverse spectrum of clinical presentation that is detectable in newborn screening. We report an 8-year-old girl with ASL deficiency who was detected through newborn screening and was confirmed using biochemical and functional assay. She is compound heterozygous for a likely pathogenic variant NM_000048.

Telomerase and hallmarks of cancer: An intricate interplay governing cancer cell evolution.

Transformed cells must acquire specific characteristics to be malignant. Weinberg and Hanahan characterize these characteristics as cancer hallmarks. Though these features are independently driven, substantial signaling crosstalk in transformed cells efficiently promotes these feature acquisitions.

Transcriptional repression by a secondary DNA binding surface of DNA topoisomerase I safeguards against hypertranscription.

Regulation of global transcription output is important for normal development and disease, but little is known about the mechanisms involved. DNA topoisomerase I (TOP1) is an enzyme well-known for its role in relieving DNA supercoils for enabling transcription. Here, we report a non-enzymatic function of TOP1 that downregulates RNA synthesis.

Mitochondria: A Potential Rejuvenation Tool against Aging.

Aging is a complex physiological process encompassing both physical and cognitive decline over time. This intricate process is governed by a multitude of hallmarks and pathways, which collectively contribute to the emergence of numerous age-related diseases. In response to the remarkable increase in human life expectancy, there has been a substantial rise in research focusing on the development of anti-aging therapies and pharmacological interventions.

Quantitative live imaging reveals a direct interaction between CD44v6 and MET in membrane domains upon activation with both MET ligands, HGF and internalin B.

Deregulation of the receptor tyrosine kinase MET/hepatocyte growth factor (HGF) pathway results in several pathological processes involved in tumor progression and metastasis. In a different context, MET can serve as an entry point for the bacterium Listeria monocytogenes, when activated by the internalin B (InlB) protein during infection of non-phagocytic cells. We have previously demonstrated that MET requires CD44v6 for its ligand-induced activation.

PAX4 loss of function increases diabetes risk by altering human pancreatic endocrine cell development.

The coding variant (p.Arg192His) in the transcription factor PAX4 is associated with an altered risk for type 2 diabetes (T2D) in East Asian populations. In mice, Pax4 is essential for beta cell formation but its role on human beta cell development and/or function is unknown.

Towards a better preclinical cancer model - human immune aging in humanized mice.

Background: Preclinical models are often used for cancer studies and evaluation of novel therapeutics. The relevance of these models has vastly improved with mice bearing a human immune system, especially in the context of immunotherapy. Nonetheless, cancer is an age-related disease, and studies often overlook the effects of aging.

Encapsulation of Human Spinal Cord Progenitor Cells in Hyaluronan-Gelatin Hydrogel for Spinal Cord Injury Treatment.

Transplanting human induced pluripotent stem cells (iPSCs)-derived spinal cord progenitor cells (SCPCs) is a promising approach to treat spinal cord injuries. However, stem cell therapies face challenges in cell survival, cell localization to the targeted site, and the control of cell differentiation. Here, we encapsulated SCPCs in thiol-modified hyaluronan-gelatin hydrogels and optimized scaffold mechanical properties and cell encapsulation density to promote cell viability and neuronal differentiation and .