Post-traumatic osteoarthritis (PTOA) is a painful joint disease characterized by the degradation of bone, cartilage, and other connective tissues in the joint. PTOA is initiated by trauma to joint-stabilizing tissues, such as the anterior cruciate ligament, medial meniscus, or by intra-articular fractures. In humans, ~50% of joint injuries progress to PTOA, while the rest spontaneously resolve.
View Article and Find Full Text PDFUnlabelled: Plaque assay is the gold standard for the quantification of viable cytopathic viruses like Zika virus (ZIKV). Some strains of ZIKV produce plaques that are very difficult to accurately visualize and count on the commonly used Vero cell line. From data generated in our lab, we became curious if Vero/TMPRSS2 cells may be a better alternative; therefore, we compared the plaque forming units of two strains of ZIKV on Vero/TMPRSS2 cells to those produced by Vero cells.
View Article and Find Full Text PDFCoccidioidomycosis, or Valley fever, is a lung disease caused by inhalation of fungi, prevalent in the Southwestern United States, Mexico, and parts of Central and South America. Annually, the United States reports 10,000-20,000 cases, although those numbers are expected to increase as climate change expands the fungal geographic range. While 60% of infections are asymptomatic, 40% symptomatic infections are often misdiagnosed due to similarities with bronchitis or pneumonia.
View Article and Find Full Text PDFFemur fracture leads to loss of bone at uninjured skeletal sites, which may increase risk of subsequent fracture. Osteocytes, the most abundant bone cells, can directly resorb bone matrix and regulate osteoclast and osteoblast activity, but their role in systemic bone loss after fracture remains poorly understood. In this study we used a transgenic (TG+) mouse model that overexpresses human B-cell lymphoma 2 (BCL-2) in osteoblasts and osteocytes.
View Article and Find Full Text PDFSkeletal fracture resistance emerges from multiple components of bone structure like microarchitecture, matrix mineralization, and organization. These characteristics are engendered via mechanisms like the hypoxia-inducible factors (HIF) pathway, involving two paralogs, HIF-1α and HIF-2α. Under normoxia, HIF-α is targeted for degradation via von-Hippel Lindau (VHL); hypoxia enables HIF-α stabilization and induction of target genes.
View Article and Find Full Text PDFAcromegaly is a rare pituitary condition stemming from hypersecretion of growth hormone (GH). Classic presentation involves enlarged hands, feet, and coarse facial features. However, late-onset cardiac manifestations develop in the absence of disease control.
View Article and Find Full Text PDFSpermatogonial stem cell (SSC) acquisition of meiotogenetic state during puberty to produce genetically diverse gametes is blocked by drugs collectively referred as 'puberty blocker' (PB). Investigating the impact of PB on juvenile SSC state and function is challenging due to limited tissue access and clinical data. Herein, we report largest clinically annotated juvenile testicular biorepository with all children with gender dysphoria on chronic PB treatment highlighting shift in pediatric patient demography in US.
View Article and Find Full Text PDFMef2c is a transcription factor that mediates key cellular behaviors that promote endochondral ossification and bone formation. Previously, Mef2c has been shown to regulate Sost transcription via its osteocyte-specific enhancer, ECR5, and conditional deletions of Mef2c with either Col1-Cre or Dmp1-Cre produced generalized high bone mass (HBM) consistent with Van Buchem Disease phenotypes. However, Sost; Mef2c; Dmp1-Cre mice produced a significantly higher bone mass phenotype that Sost alone suggesting that Mef2c modulates bone mass through additional mechanisms, independent of Sost.
View Article and Find Full Text PDFBioorg Med Chem
December 2023
In the present study, we evaluated the neuroprotective potential of Hesperidin Methyl Chalcone (HMC) against the neurotoxicity induced by Aβ peptide HMC demonstrated higher free-radical scavenging activity than Hesperidin in initial cell-free studies. Investigations using the fluorescent dye thioflavin T with Aβ peptide showed that HMC has the ability to combat extracellular amyloid aggregation by possessing anti-aggregation property against oligomers and by disaggregating mature fibrils. Also, the results of the molecular simulation studies show that HMC ameliorated oligomer formation.
View Article and Find Full Text PDFPost traumatic osteoarthritis (PTOA) is a form of secondary osteoarthritis (OA) that develops in ~50% of cases of severe articular joint injuries and leads to chronic and progressive degradation of articular cartilage and other joint tissues. PTOA progression can be exacerbated by repeated injury and systemic inflammation. Few studies have examined approaches for blunting or slowing down PTOA progression with emphasis on systemic inflammation; most arthritis studies focused on the immune system have been in the context of rheumatoid arthritis.
View Article and Find Full Text PDFA polarization-insensitive planar patch antenna, which has a large embedded serial capacitance, is proposed for constructing a metal mountable tag by using merely a single radiator. The proposed antenna structure itself contains two flaps of patches, which are very closely overlapped, for generating a large capacitive reactance for reducing the resonant frequency of the tag. It has been found that the surface currents in the overlapped region are in the reverse direction as the large capacitance is virtually placed in series.
View Article and Find Full Text PDFWe propose an unbiased methodology to rank compounds for advancement into comprehensive preclinical testing for Alzheimer's disease (AD). Translation of compounds to the clinic in AD has been hampered by poor predictive validity of models, compounds with limited pharmaceutical properties, and studies that lack rigor. To overcome this, MODEL-AD's Preclinical Testing Core developed a standardized pipeline for assessing efficacy in AD mouse models.
View Article and Find Full Text PDFMolecular oxygen levels vary during development and disease. Adaptations to decreased oxygen bioavailability (hypoxia) are mediated by hypoxia-inducible factor (HIF) transcription factors. HIFs are composed of an oxygen-dependent α subunit (HIF-α), of which there are two transcriptionally active isoforms (HIF-1α and HIF-2α), and a constitutively expressed β subunit (HIFβ).
View Article and Find Full Text PDFBackground: Gynecomastia is defined as a benign enlargement of male breast glandular tissue. It is the most common breast condition in male, and the prevalence ranges from 32% to 72%. No standardized treatment exists for gynecomastia.
View Article and Find Full Text PDFThe photoredox amination of arene protocols mostly comprises photocatalyst-mediated transformations. Herein, we presented the photocatalyst-free, visible-light promoted, direct conversion of C(sp)-H to C(sp)-N method. Multipurpose benzothiadiazoles are used as model synthons and secondary amines as aminating agents.
View Article and Find Full Text PDFOrg Biomol Chem
January 2023
The synthesis of unsymmetrical dithioacetals based on gold catalysis is described. Although many approaches to the preparation of symmetrical dithioacetals have been developed, the methods to access unsymmetrical ones remain limited. In this regard, we report a mild synthetic method with a broad substrate scope.
View Article and Find Full Text PDFMechanical unloading causes rapid loss of bone structure and strength, which gradually recovers after resuming normal loading. However, it is not well established how this adaptation to unloading and reloading changes with age. Clinically, elderly patients are more prone to musculoskeletal injury and longer periods of bedrest, therefore it is important to understand how periods of disuse will affect overall skeletal health of aged subjects.
View Article and Find Full Text PDFUnlabelled: The influence of particle size and solvent flow rate on the kinetics of oil extraction from soybean (eight fractions from 0.433 to 0.122 mm) was studied using hexane, simulating commercial percolation type extractor.
View Article and Find Full Text PDFType 1 diabetes mellitus (T1DM) affects 9.5% of the population. T1DM is characterized by severe insulin deficiency that causes hyperglycemia and leads to several systemic effects.
View Article and Find Full Text PDFHerein, we present a tandem aza-Michael addition-vinylogous aldol condensation strategy for the synthesis of -bridged pyridine fused quinolone derivatives from quinolones and ynones. The presented tandem transformation features the construction of C-N and CC bonds in a single operation, under transition metal-free conditions. The wide substrate scope and gram scale synthesis of pyridine fused quinolone derivatives expand the synthetic value of the presented protocol.
View Article and Find Full Text PDFRomosozumab, a humanized monoclonal antibody specific for sclerostin (SOST), has been approved for treatment of postmenopausal women with osteoporosis at a high risk for fracture. Previous work in sclerostin global knockout () mice indicated alterations in immune cell development in the bone marrow (BM), which could be a possible side effect in romosozumab-treated patients. Here, we examined the effects of short-term sclerostin depletion in the BM on hematopoiesis in young mice receiving sclerostin antibody (Scl-Ab) treatment for 6 weeks, and the effects of long-term deficiency on wild-type (WT) long-term hematopoietic stem cells transplanted into older cohorts of mice.
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