Targeting CD84 protein on myeloid-derived suppressor cells as a novel immunotherapy in solid tumors.

Background And Objective: Myeloid-derived suppressor cells (MDSCs) are a crucial and diverse group of cells found in the tumor microenvironment (TME) that facilitate progression, invasion, and metastasis within solid tumors. CD84, a homophilic adhesion molecule expressed on MDSCs, plays a critical role in their accumulation and function within the TME. This study aims to investigate the protein-protein interactions of CD84 using molecular dynamics simulations and to explore potential therapeutic strategies targeting these interactions.

Synthetic cells in tissue engineering.

Tissue functions rely on complex structural, biochemical, and biomechanical cues that guide cellular behavior and organization. Synthetic cells, a promising new class of biomaterials, hold significant potential for mimicking these tissue properties using simplified, nonliving building blocks. Advanced synthetic cell models have already shown utility in biotechnology and immunology, including applications in cancer targeting and antigen presentation.

Lysosomal dysfunction and inflammatory sterol metabolism in pulmonary arterial hypertension.

Vascular inflammation regulates endothelial pathophenotypes, particularly in pulmonary arterial hypertension (PAH). Dysregulated lysosomal activity and cholesterol metabolism activate pathogenic inflammation, but their relevance to PAH is unclear. Nuclear receptor coactivator 7 () deficiency in endothelium produced an oxysterol and bile acid signature through lysosomal dysregulation, promoting endothelial pathophenotypes.

Elevated Neutrophil-to-Lymphocyte Ratio Predicts Prognosis in Acute Myocarditis.

Background: Neutrophil-to-lymphocyte ratio (NLR) is an easy-to-use inflammatory biomarker. Baseline NLR is independently associated with incident cardiovascular events and all-cause mortality. However, whether this applies to acute myocarditis (AM) has not been evaluated.

Harnessing Anti-Inflammatory and Regenerative Potential: GelMA Hydrogel Loaded with IL-10 and Kartogenin for Intervertebral Disc Degeneration Therapy.

Intervertebral disc degeneration (IVDD) is a major contributor to chronic back pain and disability, with limited effective therapeutic options. Current treatment options, including conservative management and surgical interventions, often fail to effectively halt disease progression and come with notable side effects. IVDD is characterized by the breakdown of the extracellular matrix (ECM) and the infiltration of inflammatory cells, which exacerbate disc degeneration.

Billion-Scale Expansion of Functional hiPSC-Derived Cardiomyocytes in Bioreactors Through Oxygen Control and Continuous Wnt Activation.

Generation of upscaled quantities of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), for therapeutic or testing applications, is both expensive and time-consuming. Herein, a scalable bioprocess for hiPSC-CM expansion in stirred-tank bioreactors (STB) is developed. By combining the continuous activation of the Wnt pathway, through perfusion of CHIR99021, within a mild hypoxia environment, the expansion of hiPSC-CM as aggregates is maximized, reaching 4 billion of pure hiPSC-CM in 2L STB.

Biomolecular Microneedle Initiates FeO/MXene Heterojunction-Mediated Nanozyme-Like Reactions and Bacterial Ferroptosis to Repair Diabetic Wounds.

Reactive oxygen species (ROS) play a dual role in wound healing. They act as crucial signaling molecules and antimicrobial agents when present at moderate levels. However, excessive levels of ROS can hinder the healing process for individuals with diabetes.

Loss of Type 2 Bone Morphogenetic Protein Receptor Activates NOD-Like Receptor Family Protein 3/Gasdermin E-Mediated Pyroptosis in Pulmonary Arterial Hypertension.

Background: Pulmonary arterial hypertension (PAH) is an incurable disease initiated by endothelial dysfunction, secondary to vascular inflammation and occlusive pulmonary arterial vascular remodeling, resulting in elevated pulmonary arterial pressure and right heart failure. Previous research has reported that dysfunction of type 2 bone morphogenetic protein receptor (BMPR2) signaling pathway in endothelium is inclined to prompt inflammation in PAH models, but the underlying mechanism of BMPR2 deficiency-mediated inflammation needs further investigation. This study was designed to investigate whether BMPR2 deficiency contributes to pulmonary arterial hypertension via the NLRP3 (NOD-like receptor family protein 3)/GSDME (gasdermin E)-mediated pyroptosis pathway.

Adhesive and Conductive Fibrous Hydrogel Bandages for Effective Peripheral Nerve Regeneration.

Peripheral nerve injury is a common disease resulting in reversible and irreversible impairments of motor and sensory functions. In addition to conventional surgical interventions such as nerve grafting and neurorrhaphy, nerve guidance conduits are used to effectively support axonal growth without unexpected neuroma formation. However, there are still challenges to secure tissue-mimetic mechanical and electrophysiological properties of the conduit materials.

DNA2 knockout aggravates cerebral ischemia/reperfusion injury by reducing postsynaptic Homer1a.

DNA2, a multifunctional enzyme with structure-specific nuclease, 5 -to-3 helicase, and DNA-dependent ATPase activities, plays a pivotal role in the cellular response to DNA damage. However, its involvement in cerebral ischemia/reperfusion (I/R) injury remains to be elucidated. This study investigated the involvement of DNA2 in cerebral I/R injury using conditional knockout (cKO) mice ( -Cre) subjected to middle cerebral artery occlusion (MCAO), an established model of cerebral I/R.

Impact of eggshell membrane on metabolism and cell adhesion in oxidatively stressed canine chondrocytes.

Eggshell membrane (ESM) is a rich source of bioactive compounds, including proteins, peptides, and antioxidants, contributing to its potential therapeutic benefits. These natural antioxidants might help neutralize reactive oxygen species (ROS) and modulate inflammatory responses, which are often linked with chondrocyte damage in osteoarthritis. In this study, we investigated the functional effects of ESM proteins on HO-induced oxidative stress in a neonatal canine chondrocytes.

High-grade liver injury: outcomes with a trauma surgery-liver surgery collaborative approach.

Background: Operative mortality for high-grade liver injury (HGLI) remains 42% to 66%, with near-universal mortality after retrohepatic caval injury. The objective of this study was to evaluate mortality and complications of operative and nonoperative management (OM and NOM) of HGLI at our institution, characterized by a trauma surgery-liver surgery collaborative approach to trauma care.

Methods: This was an observational cohort study of adult patients (age ≥16) with HGLI (The American Association for Surgery of Trauma (AAST) grades IV and V) admitted to an urban level I trauma center from January 2010 to November 2021.

Treatment with Autologous Adipose-derived Regenerative Cells for Peyronie's Disease in Men: The Straight @head Pilot Study.

Background And Objective: We evaluated the effectiveness of injecting autologous adipose-derived regenerative cells (ADRCs) into plaque in men with chronic Peyronie's disease (PD).

Methods: This pilot safety study recruited 22 Danish men with chronic PD from an outpatient clinic. Patients received one bolus of ADRCs injected into plaque, with follow-ups at 1, 3, 6, and 12 mo.

A biocompatible β-cyclodextrin inclusion complex containing natural extracts: a promising antibiofilm agent.

Biofilms formed by several bacterial strains still pose a significant challenge to healthcare due to their resistance to conventional treatment approaches, including antibiotics. This study explores the potential of loading natural extracts with antimicrobial activities into β-cyclodextrin (βCD) nanoparticles, which are FDA-approved and have superior biocompatibility owing to their cyclic sugar structures, for biofilm eradication. An inclusion complex of βCD carrying essential oils (BOS) was prepared and characterized with regard to its physicochemical properties, antimicrobial efficacy, and antibiofilm activities.

3D bio-printed proteinaceous bioactive scaffold loaded with dual growth factor enhanced chondrogenesis and in situ cartilage regeneration.

Articular cartilage has a limited self-healing capacity, leading to joint degeneration and osteoarthritis over time. Therefore, bioactive scaffolds are gaining attention as a promising approach to regenerating and repairing damaged articular cartilage through tissue engineering. In this study, we reported on a novel 3D bio-printed proteinaceous bioactive scaffolds combined with natural porcine cancellous bone dECM, tempo-oxidized cellulose nanofiber (TOCN), and alginate carriers for TGF-β1, FGF-18, and ADSCs to repair cartilage defects.

Viral-based gene therapy clinical trials for immune deficiencies and blood disorders from 2013 until 2023 - an overview.

Gene therapy (GT) as a groundbreaking approach holds promise for treating many diseases including immune deficiencies and blood disorders. GT can benefit patients suffering from these diseases, especially those without matched donors or who are at risk after hematopoietic stem cell transplantation (HSCT). Due to all the advances in the field of GT, its main challenge is still gene delivery.

CD4-Derived Double-Negative T Cells Ameliorate Alzheimer's Disease-Like Phenotypes in the 5×FAD Mouse Model.

Background: Alzheimer's disease (AD) is a debilitating neurodegenerative disorder that is difficult to predict and is typically diagnosed only after symptoms manifest. Recently, CD4 T cell-derived double-negative T (DNT) cells have shown strong immuno-regulatory properties in both in vitro and in vivo neuronal inflammation studies. However, the effectiveness of DNT cells in treating on AD are not yet fully understood.

Basic Fibroblast Growth Factor-Releasing Polyglycolic Acid Duras Improve Neurological Function after Cerebral Infarction.

Objective: Regenerative therapy using stem cells to treat cerebral infarction is currently in the research phase. However, this method is costly. It also faces other significant challenges, including optimization of timing, delivery methods, and dosage.

Tissue-specific modulation of CRISPR activity by miRNA-sensing guide RNAs.

Nucleic acid nanostructures offer unique opportunities for biomedical applications due to their sequence-programmable structures and functions, which enable the design of complex responses to molecular cues. Control of the biological activity of therapeutic cargoes based on endogenous molecular signatures holds the potential to overcome major hurdles in translational research: cell specificity and off-target effects. Endogenous microRNAs (miRNAs) can be used to profile cell type and cell state, and are ideal inputs for RNA nanodevices.

Synthesis, Molecular Docking, Antimicrobial, and Antioxidant Evaluation of Novel Dithiazole and Thiazole Derivatives.

Introduction: An efficient procedure was reported for the synthesis of novel hybrid dithiazoles 7 and thiazoles 15, in good yields, by applying hydrazonyl chlorides 4 with thiocarbohydrazone derivatives 3 and 12.

Methods: The thiazole derivatives were evaluated for their antimicrobial and antioxidant activities.

Results: According to the results, thiazoles revealed marked potency as antimicrobial and antioxidant agents.

Mechanism of hyperbaric oxygen therapy downregulating H-type angiogenesis in subchondral bone of knee osteoarthritis through the PHD2/HIF-1α pathway.

Objective: To explore the mechanism of hyperbaric oxygen therapy in inhibiting subchondral bone angiogenesis and delaying the progression of osteoarthritis through the PHD2/HIF-1α signaling pathway.

Methods: Mice were randomly divided into three groups (control group, osteoarthritis group, and hyperbaric oxygen treatment group). The effect of hyperbaric oxygen therapy on osteoarthritis was evaluated using Micro-CT, Safranin O-Fast Green staining, and detection of osteoarthritis inflammation markers (MMP-13, ADAMTS-5, Col2a1, and Aggrecan).

Neutrophil extracellular traps (NETs) are increased in rheumatoid arthritis-associated interstitial lung disease.

Background: Neutrophil extracellular trap (NET) formation has been implicated as a pathogenic mechanism in both rheumatoid arthritis (RA) and interstitial lung disease (ILD). However, the role of NETs in RA-associated ILD (RA-ILD) and the mechanisms driving NET formation remain unclear. This study aimed to assess the involvement of NETs in RA-ILD and elucidate the underlying mechanisms.

Multiscale footprints reveal the organization of cis-regulatory elements.

Cis-regulatory elements (CREs) control gene expression and are dynamic in their structure and function, reflecting changes in the composition of diverse effector proteins over time. However, methods for measuring the organization of effector proteins at CREs across the genome are limited, hampering efforts to connect CRE structure to their function in cell fate and disease. Here we developed PRINT, a computational method that identifies footprints of DNA-protein interactions from bulk and single-cell chromatin accessibility data across multiple scales of protein size.

RELMβ sets the threshold for microbiome-dependent oral tolerance.

Tolerance to dietary antigens is critical for avoiding deleterious type 2 immune responses resulting in food allergy (FA) and anaphylaxis. However, the mechanisms resulting in both the maintenance and failure of tolerance to food antigens are poorly understood. Here we demonstrate that the goblet-cell-derived resistin-like molecule β (RELMβ) is a critical regulator of oral tolerance.