Interspecies transcriptome profiles of human T cell activation and liver inflammation in a xenogeneic graft-versus-host disease model.

Background: Xenogeneic transplantation induces acute graft-versus-host disease (aGvHD) and subsequent vital organ damage. Herein, we aimed to examine hepatic damage associated with aGvHD using histopathology and gene expression profiles.

Methods: A xenografic GvHD model was established by engrafting human peripheral blood mononuclear cells (PBMCs) into immunodeficient NOD-scid IL2Rγnull (NSG) mice after busulfan conditioning.

Amplified response of drug-induced liver fibrosis immune cell co-culture in a 3D hepatic fibrosis model.

Liver fibrosis, a critical consequence of chronic liver diseases, is characterized by excessive extracellular matrix (ECM) deposition driven by inflammation. This process involves complex interactions among hepatocytes, hepatic stellate cells (HSCs), and Kupffer cells, the liver's resident macrophages. Kupffer cells are essential in initiating fibrosis through the release of pro-inflammatory cytokines that activate HSCs.

In Vitro Nonalcoholic Fatty Liver Disease Model Elucidating the Effect of Immune Environment on Disease Progression and Alleviation.

Nonalcoholic fatty liver disease (NAFLD), which is a major cause of chronic liver disease, is characterized by fat accumulation in the liver. Existing models struggle to assess medication effects on liver function in the context of NAFLD's unique inflammatory environment. We address this by developing a 3D in vitro NAFLD model using HepG2 and THP-1 cells (mimicking liver and Kupffer cells) cocultured using transwell and hydrogel system.

Cyclosporine A-induced systemic metabolic perturbations in rats: A comprehensive metabolome analysis.

A better understanding of cyclosporine A (CsA)-induced nephro- and hepatotoxicity at the molecular level is necessary for safe and effective use. Utilizing a sophisticated study design, this study explored metabolic alterations after long-term CsA treatment in vivo. Rats were exposed to CsA with 4, 10, and 25 mg/kg for 4 weeks and then sacrificed to obtain liver, kidney, urine, and serum for untargeted metabolomics analysis.

The Effects of Busulfan on Xenogeneic Transplantation of Human Peripheral Blood Mononuclear Cells in Recipient Mice.

Background: Humanized mouse models with engraftment of human peripheral blood mononuclear cells (PBMCs) or hematopoietic stem cells (HSCs) are effective tools for the study of human immunity. Busulfan has been used as a substitute for irradiation in human hematopoietic stem cell (HSC) transplantation models, but it has not been tested in human peripheral blood mononuclear cell (PBMC) transplantation models.

Methods: This study evaluated PBMC engraftment using cytometry and enzyme-linked immunosorbent assay (ELISA) in female NOD.

LC-MS-Based Direct Quantification of MicroRNAs in Rat Blood.

MicroRNA (miRNA) has recently garnered significant research attention, owing to its potential as a diagnostic biomarker and therapeutic target. Liquid chromatography-mass spectrometry (LC-MS) offers accurate quantification, multiplexing capacity, and high compatibility with various matrices. These advantages establish it as a preferred technique for detecting miRNA in biological samples.

genome editing using 244- LNPs and low-dose AAV achieves therapeutic threshold in hemophilia A mice.

Gene therapy and rebalancing therapy have emerged as promising approaches for treating hemophilia A, but there are limitations, such as temporary efficacy due to individual differences. Genome editing for hemophilia has shown long-term therapeutic potential in preclinical trials. However, a cautious approach is necessary because genome editing is irreversible.

Development of an In Vitro Model for Inflammation Mediated Renal Toxicity Using 3D Renal Tubules and Co-Cultured Human Immune Cells.

Background: The emergence of various infectious diseases and the toxic effects of hyperinflammation by biotherapeutics have highlighted the need for in vitro preclinical models mimicking the human immune system. In vitro models studying the relationship between hyperinflammation and acute renal injury mainly rely on 2D culture systems, which have shown limitations in recapitulating kidney function. Herein, we developed an in vitro kidney toxicity model by co-culturing 3D engineered kidney proximal tubules cells (RPTEC/TERT1) with human peripheral blood mononuclear cells (PBMC).

Pathway-level multi-omics analysis of the molecular mechanisms underlying the toxicity of long-term tacrolimus exposure.

Tacrolimus (TAC)-based treatment is associated with nephrotoxicity and hepatotoxicity; however, the underlying molecular mechanisms responsible for this toxicity have not been fully explored. This study elucidated the molecular processes underlying the toxic effects of TAC using an integrative omics approach. Rats were sacrificed after 4 weeks of daily oral TAC administration at a dose of 5 mg/kg.

Preclinical Evaluation of interferon-gamma primed human Wharton's jelly-derived mesenchymal stem cells.

The potential of human mesenchymal stem cells (MSCs) for cell therapy has been investigated in numerous immune-mediated conditions; MSCs are considered one of the most promising cellular therapeutics to treat intractable diseases. Recently, approaches to prime MSCs have been investigated, thereby generating cellular products with enhanced potential for a variety of clinical applications. Interferon-gamma (IFN-γ) priming is a current approach used to increase the therapeutic efficacy of MSCs.

Transition Metal β-Diketonate Adhesion Promoters in Epoxy-Anhydride Resin.

Epoxy to copper adhesion supports the reliability of numerous structures in electronic packaging. Compared to substrate pre-treatment, processing and cost considerations are in favor of adhesion promoters loaded in epoxy formulations. In this work, first row transition metal β-diketonates present such a compelling case when added in epoxy/anhydride resins: over 30% (before moisture aging) and 50% (after moisture aging) enhancement in lap shear strength are found using Co(II) and Ni(II) hexafluoroacetylacetonate.

Systems-level multi-omics characterization provides novel molecular insights into indomethacin toxicity.

The mechanism of indomethacin toxicity at the systemic level is largely unknown. In this study, multi-specimen molecular characterization was conducted in rats treated with three doses of indomethacin (2.5, 5, and 10 mg/kg) for 1 week.

A general toxicity and biodistribution study of human natural killer cells by single or repeated intravenous dose in severe combined immune deficient mice.

Natural killer (NK) cells are a part of the innate immune system and represent the first line of defense against infections and tumors. NK cells can eliminate tumor cells without major histocompatibility restriction and are independent of the expression of tumor-associated antigens. Therefore, they are considered an emerging tool for cancer immunotherapy.

Bisphenol A impairs renal function by reducing Na/K-ATPase and F-actin expression, kidney tubule formation in vitro and in vivo.

The kidney proximal tubule is responsible for reabsorbing water and NaCl to maintain the homeostasis of the body fluids, electrolytes, and nutrients. Thus, abnormal functioning of the renal proximal tubule can lead to life-threatening imbalances. Bisphenol A (BPA) has been used for decades as a representative chemical in household plastic products, but studies on its effects on the kidney proximal tubule are insufficient.

Tumorigenicity Assessment of Human Cancer Cell Lines Xenografted on Immunodeficient Mice as Positive Controls of Tumorigenicity Testing.

Recent advances in human pluripotent stem cell (hPSC)-derived cell therapies and genome editing technologies such as CRISPR/Cas9 make regenerative medicines promising for curing diseases previously thought to be incurable. However, the possibility of off-target effects during genome editing and the nature of hPSCs, which can differentiate into any cell type and infinitely proliferate, inevitably raises concerns about tumorigenicity. Tumorigenicity acts as a major obstacle to the application of hPSC-derived and gene therapy products in clinical practice.

Decellularized Human Adipose Tissue as an Alternative Graft Material for Bone Regeneration.

Background: Tissue engineering approaches to treat damaged bone include various tissue transplants such as autologous, allogeneic, and xenografts. Artificial materials have been widely introduced to meet the demand for graft materials, but insufficiency in supply is still not resolved. In this study, human adipose tissue, easily obtained from the human body, was harvested, and the tissue was decellularized to fabricate a decellularized human adipose tissue matrix (DM) as an alternative graft material.

Nephrotoxicity evaluation and proteomic analysis in kidneys of rats exposed to thioacetamide.

Thioacetamide (TAA) was administered orally at 0, 10, and 30 mg/kg body weight (BW) daily to Sprague-Dawley rats aged 6-7 weeks for 28 consecutive days. Nephrotoxicity and proteomics were evaluated in the kidneys of rats exposed to TAA. The BW decreased, however, the relative kidneys weight increased.

Characteristics of Extracellular Vesicles and Preclinical Testing Considerations Prior to Clinical Applications.

Cell therapy products have significant limitations, such as storage instability, difficulties with transportation, and toxicity issues such as tumorigenicity and immunogenicity. Extracellular vesicles (EVs) secreted from cells show potential for therapeutic agent development. EVs have not been widely examined as investigational drugs, and non-clinical studies for the clinical approval of EV therapeutic agents are challenging.

Identification of integrative hepatotoxicity induced by lysosomal phospholipase A2 inhibition of cationic amphiphilic drugs via metabolomics.

Drug-induced liver injury (DILI) is a condition caused by drugs that leads to abnormal hepatic function. Hepatotoxicity caused by DILI has been shown to be due to cellular stress, mitochondrial dysfunction, cell necrosis and apoptosis and many types of hepatotoxicity, such as phospholipidosis, steatosis and hepatitis, commonly share intracellular molecular mechanisms. Metabolomics can be useful for mechanism-based toxicity evaluations and has been recently utilized as a scientific technique that can effectively predict the risk factors for chemical substances.

Adipose stem cell-derived extracellular vesicles ameliorates corticosterone-induced apoptosis in the cortical neurons via inhibition of ER stress.

Background: Corticosterone (CORT) can induce neuronal damage in various brain regions, including the cerebral cortex, the region implicated in depression. However, the underlying mechanisms of these CORT-induced effects remain poorly understood. Recently, many studies have suggested that adipose stem cell-derived extracellular vesicles (A-EVs) protect neurons in the brain.

Difluorobenzylamine Treatment of Organolead Halide Perovskite Boosts the High Efficiency and Stability of Photovoltaic Cells.

As one of the most competitive light-harvesting materials, organometal halide perovskites have attracted great attention due to their low-cost and top-down solution fabricability. However, the instability of perovskites in a moist environment reduces the potential for their commercialization. In this study, novel 2,4-fluorobenzylamine (FBA) was employed as the passivation material, which could successfully suppress the defects and improve the moisture resistance of perovskites, resulting in an ultrahigh power conversion efficiency of 17.

Biomarker LEPRE1 induces pelitinib-specific drug responsiveness by regulating ABCG2 expression and tumor transition states in human leukemia and lung cancer.

Biomarkers for treatment sensitivity or drug resistance used in precision medicine include prognostic and predictive molecules, critical factors in selecting appropriate treatment protocols and improving survival rates. However, identification of accurate biomarkers remain challenging due to the high risk of false-positive findings and lack of functional validation results for each biomarker. Here, we discovered a mechanical correlation between leucine proline-enriched proteoglycan 1 (LEPRE1) and pelitinib drug sensitivity using in silico statistical methods and confirmed the correlation in acute myeloid leukemia (AML) and A549 lung cancer cells.

Atomic Modulation of 3D Conductive Frameworks Boost Performance of MnO for Coaxial Fiber-Shaped Supercapacitors.

Coaxial fiber-shaped supercapacitors are a promising class of energy storage devices requiring high performance for flexible and miniature electronic devices. Yet, they are still struggling from inferior energy density, which comes from the limited choices in materials and structure used. Here, Zn-doped CuO nanowires were designed as 3D framework for aligned distributing high mass loading of MnO nanosheets.

Melt Processable Novolac Cyanate Ester/Biphenyl Epoxy Copolymer Series with Ultrahigh Glass-Transition Temperature.

The rapid progress in silicon carbide (SiC)-based technology for high-power applications expects an increasing operation temperature (up to 250 °C) and awaits reliable packaging materials to unleash their full power. Epoxy-based encapsulant materials failed to provide satisfactory protection under such high temperatures due to the intrinsic weakness of epoxy resins, despite their unmatched good adhesion and processability. Herein, we report a series of copolymers made by melt blending novolac cyanate ester and tetramethylbiphenyl epoxy (NCE/EP) that have demonstrated much superior high-temperature stability over current epoxies.