Inhibition of acyl-CoA synthetase long-chain isozymes decreases multiple myeloma cell proliferation and causes mitochondrial dysfunction.

Multiple myeloma (MM) is an incurable cancer of plasma cells with a 5-year survival rate of 59%. Dysregulation of fatty acid (FA) metabolism is associated with MM development and progression; however, the underlying mechanisms remain unclear. Herein, we explore the roles of long-chain fatty acid coenzyme A ligase (ACSL) family members in MM.

Comparative Sensitivity of MRI Indices for Myelin Assessment in Spinal Cord Regions.

Although multiple magnetic resonance imaging (MRI) indices are known to be sensitive to the noninvasive assessment of myelin integrity, their relative sensitivities have not been directly compared. This study aimed to identify the most sensitive MRI index for characterizing myelin composition in the spinal cord's gray matter (GM) and white matter (WM). MRI was performed on a deer's ex vivo cervical spinal cord.

Emergence of Near-Infrared Photoluminescence via ZnS Shell Growth on the AgBiS Nanocrystals.

AgBiS nanocrystals (NCs), composed of nontoxic, earth-abundant materials and exhibiting an exceptionally high absorption coefficient from visible to near-infrared (>10 cm), hold promise for photovoltaics but have lack of photoluminescence (PL) due to intrinsic nonradiative recombination and challenging shell growth. In this study, we reported a facile wet-chemical approach for the epitaxial growth of ZnS shell on AgBiS NCs, which triggered the observation of PL emission in the near-infrared (764 nm). Since high quality of the core is critical for epitaxial shell growth, we first obtained rock-salt structured AgBiS NCs with high crystallinity, nearly spherical shape and monodisperse size distribution (<6%) via a dual-ligand approach reacting Ag-Bi oleate with elemental sulfur in oleylamine.

Recent progress in CRISPR/Cas9 system for eye disorders.

Ocular disorders encompass a broad spectrum of phenotypic and clinical symptoms resulting from several genetic variants and environmental factors. The unique anatomy and physiology of the eye facilitate validation of cutting-edge gene editing treatments. Genome editing developments have allowed researchers to treat a variety of diseases, including ocular disorders.

Advances in applications of the CRISPR/Cas9 system for respiratory diseases.

Genetic and environmental factors can have an impact on lung and respiratory disorders which are associated with severe symptoms and have high mortality rates. Many respiratory diseases are significantly influenced by genetic or epigenetic factors. Gene therapy offers a powerful approach providing therapeutic treatment for lung diseases.

Contribution of long-lived plasma cells to antibody-mediated allograft rejection.

Persistent alloantigens derived from allograft tissues can be recognized by the host's alloreactive immune system. This process enables cognate B cells to differentiate into plasma cells, which secrete donor-specific antibodies that are key drivers of antibody-mediated allograft rejection. A subset of these plasma cells can survive for extended periods in a suitable survival niche and mature into long-lived plasma cells (LLPCs), which are a cellular component of humoral memory.

Mitochondrial Transplantation Ameliorates Pulmonary Fibrosis by Suppressing Myofibroblast Activation.

Idiopathic pulmonary fibrosis (IPF) is a pulmonary disease characterized by excessive extracellular matrix protein deposition in the lung interstitium, subsequently causing respiratory failure. IPF still has a high medical unmet requirement due to the lack of effective treatments to inhibit disease progression. The etiology of IPF remains unclear, but mitochondrial dysfunction is considered to be associated with IPF development.

Wnt5a exacerbates pathological bone features and trabecular bone loss in curdlan-injected SKG mice via osteoclast activation.

Many studies on osteoblasts have suggested that Wnt5a plays a crucial role in excessive osteoblast activity, which is responsible for ectopic new bone formation, but research on osteoclasts in ankylosing spondylitis (AS) remains relatively limited. This study aimed to explore whether Wnt5a influences osteoclast-mediated bone resorption in curdlan-injected SKG mice, a model that mimics AS. Compared to the Vehicle group, the Wnt5a treatment group exhibited statistically higher clinical arthritis scores and increased hindpaw thickness values.

The early transition to cold-induced browning in mouse subcutaneous white adipose tissue (scWAT) involves proteins related to nerve remodeling, cytoskeleton, mitochondria, and immune cells.

White adipose tissue (WAT) is a dynamic organ capable of remodelling in response to metabolic state. For example, in response to stimuli such as cold exposure, WAT can develop inducible brown adipocytes ('browning') capable of non-shivering thermogenesis, through concurrent changes to mitochondrial content and function. This is aided by increased neurite outgrowth and angiogenesis across the tissue, providing the needed neurovascular supply for uncoupling protein 1 activation.

Development of a Myogenin minimal promoter-based system for visualizing the degree of myogenic differentiation.

Myogenic differentiation plays a fundamental role in myogenesis during development and in muscle regeneration. Sequential expression of myogenic regulatory factors (MRFs) including myogenin in the progenitor cells triggers the expression of effector proteins such as myosin heavy chain (MHC), leading to the terminal muscle differentiation. Although we have a snapshot-like understanding of molecules at each stage of the differentiation, how these molecules are interrelated in the continuum of myogenic differentiation remains poorly understood.

Cellular Characteristics and Protein Signatures of Human Adipose Tissues from Donors With or Without Advanced Coronary Artery Disease.

: Perivascular adipose tissue (PVAT) exerts a paracrine effect on blood vessels and our objective was to understand PVAT molecular signatures related to cardiovascular disease. : We studied two groups: those undergoing mitral valve repair/replacement (VR, n = 16) and coronary artery bypass graft (CABG, n = 38). VR donors did not have coronary artery disease, whereas CABG donors had advanced coronary artery disease.

Thymidine Phosphorylase Imaging Probe for Differential Diagnosis of Metabolic dysfunction-associated Steatohepatitis.

Purpose: Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises simple steatosis (SS), which has a low risk of mortality, and metabolic dysfunction-associated steatohepatitis (MASH), which can progress to liver cirrhosis and hepatocellular carcinoma. Because differentiation between MASH and SS is the most important issue in the diagnosis of MASLD, the establishment of noninvasive diagnostic methods is urgently needed. In this study, we evaluated the potential of [I]IIMU, a thymidine phosphorylase (TYMP) targeted SPECT imaging probe, for differential diagnosis of MASLD in a preclinical animal model.

Complement factor H-related protein 5 alleviates joint inflammation and osteoclast differentiation by disrupting RANK-JNK signaling in collagen antibody-induced arthritis mouse model.

Background: Complement Factor H-Related protein 5 (CFHR5) belongs to the factor H/CFHR family and regulates the complement system by modulating factor H's inhibitory activity against C3b. Despite its known role, the impact of CFHR5 on autoimmune arthritis and its relationship to pathophysiological changes in arthritis and bone loss remain unclear. This study aimed to assess the effect of CFHR5 on aggressive osteoclast activity and arthritis using a murine model of collagen antibody-induced arthritis (CAIA).

GPCR Inhibitors Have Antiviral Properties against JC Polyomavirus Infection.

JC polyomavirus (JCPyV) infects the majority of the population and initially establishes a persistent but asymptomatic infection of the kidneys. In healthy individuals, the infection remains controlled by the host immune system, but for individuals experiencing prolonged immunosuppression, the infection can reactivate and spread to the brain, where it causes progressive multifocal leukoencephalopathy (PML), which is a fatal neurodegenerative disease. Currently, there are no approved therapies to treat PML, and affected individuals suffer rapid motor weakness and cognitive deterioration.

Enhancing Drug Solubility, Bioavailability, and Targeted Therapeutic Applications through Magnetic Nanoparticles.

Biological variability poses significant challenges in the development of effective therapeutics, particularly when it comes to drug solubility and bioavailability. Poor solubility across varying physiological conditions often leads to reduced absorption and inconsistent therapeutic outcomes. This review examines how nanotechnology, especially through the use of nanomaterials and magnetic nanoparticles, offers innovative solutions to enhance drug solubility and bioavailability.

ALK1 Signaling in Human Cardiac Progenitor Cells Promotes a Pro-angiogenic Secretome.

Pro-angiogenic paracrine/autocrine signaling impacts myocardial repair in cell-based therapies. Activin A receptor-like type 1 (, ALK1) signaling plays a pivotal role in cardiovascular development and maintenance, but its importance in human-derived therapeutic cardiac cells is not well understood. Here, we isolated a subpopulation of human highly proliferative cells (hHiPCs) from adult epicardial tissue and found that they express ALK1, a high affinity receptor for bone morphogenetic protein-9 (BMP9), which signals via SMAD1/5 to regulate paracrine/autocrine signaling and angiogenesis.

Clinical Oversight and Delayed Diagnosis of a Pathological Compression Fracture Causing Paraplegia.

While osteoporosis is the primary cause of vertebral compression fractures (VCFs), it's crucial to promptly recognize pathological fractures through comprehensive diagnostic tests, including vertebral biopsies, to determine the exact etiology. For instance, a 66-year-old male with osteoporosis experienced worsening lower limb weakness and back pain after an initial vertebroplasty for a T12 compression fracture. Subsequent MRI revealed severe circumferential extradural compression at T12, leading to further surgeries that eventually uncovered metastatic adenocarcinoma from a pancreatic tumor.

Single-cell and bulk transcriptional profiling of mouse ovaries reveals novel genes and pathways associated with DNA damage response in oocytes.

Immature oocytes enclosed in primordial follicles stored in female ovaries are under constant threat of DNA damage induced by endogenous and exogenous factors. Checkpoint kinase 2 (CHEK2) is a key mediator of the DNA damage response (DDR) in all cells. Genetic studies have shown that CHEK2 and its downstream targets, p53, and TAp63, regulate primordial follicle elimination in response to DNA damage.

A cochlear progenitor pool influences patterning of the mammalian sensory epithelium via MYBL2.

During embryonic development, Wnt signaling influences both proliferation and sensory formation in the cochlea. How this dual nature of Wnt signaling is coordinated is unknown. In this study, we define a novel role for a Wnt-regulated gene, Mybl2, which was already known to be important for proliferation, in determining the size and patterning of the sensory epithelium in the murine cochlea.