The Autocrine Role of Proteoglycan-4 (PRG4) in Modulating Osteoarthritic Synoviocyte Proliferation and Expression of Matrix Degrading Enzymes

Background: Lubricin/proteoglycan 4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes. Recently, we showed that recombinant human PRG4 (rhPRG4) is a putative ligand for CD44 receptor. rhPRG4-CD44 interaction inhibits cytokine-induced rheumatoid arthritis synoviocyte proliferation. The objective of this study is to decipher the autocrine function of PRG4 in regulating osteoarthritic synoviocyte proliferation and expression of catabolic and pro-inflammatory mediators under basal and interleukin-1 beta (IL-1β)- stimulated conditions. Methods: Cytosolic and nuclear levels of nuclear factor kappa B (NFκB) p50 and p65 subunits in Prg4+/+ and Prg4-/- synoviocytes were studied using western blot. Nuclear translocation of p50 and p65 proteins in osteoarthritis (OA) fibroblast-like synoviocytes (FLS) in response to IL-1β stimulation in the absence or presence of rhPRG4 was studied using DNA binding assays. OA synoviocyte (5000 cells per well) proliferation following IL-1β (20 ng/ml) treatment in the absence or presence of rhPRG4 (50–200 μg/ml) over 48 hours was determined using a colorimetric assay. Gene expression of matrix metalloproteinases (MMPs), tissue inhibitor of metallproteinases-1 (TIMP-1), TIMP-2, IL-1β, IL-6, IL- 8, TNF-α, cycloxygenae-2 (COX2) and PRG4 in unstimulated and IL-1β (1 ng/ml)-stimulated OA synoviocytes, in the presence or absence of rhPRG4 (100 and 200 μg/ml), was studied following incubation for 24 hours. Results: Prg4-/- synoviocytes contained higher nuclear p50 and p65 levels compared to Prg4+/+ synoviocytes (p \u3c 0. 05). rhPRG4 (100 μg/ml) reduced p50 and p65 nuclear levels in Prg4+/+ and Prg4-/- synoviocytes (p \u3c 0.001). Similarly, rhPRG4 (200 μg/ml) inhibited NFκB translocation and cell proliferation in OA synoviocytes in a CD44-dependent manner (p \u3c 0.001) via inhibition of IκBα phosphorylation. IL-1β reduced PRG4 expression in OA synoviocytes and rhPRG4 (100 μg/ml) treatment reversed this effect (p \u3c 0.001). rhPRG4 (200 μg/ml) reduced basal gene expression of MMP-1, MMP-3, MMP-13, IL-6, IL-8, and PRG4 in OA synoviocytes, while increasing TIMP-2 and cycloxygenase-2 (COX2) expression (p \u3c 0.001). rhPRG4 (200 μg/ml) reduced IL-1β induction of MMP-1, MMP-3, MMP-9, MMP-13, IL-6, IL-8, and COX2 expression in a CD44-dependent manner (p \u3c 0.001). Conclusion: PRG4 plays an important anti-inflammatory role in regulating OA synoviocyte proliferation and reduces basal and IL-1β-stimulated expression of catabolic mediators. Exogenous rhPRG4 autoregulates native PRG4 expression in OA synoviocytes

Barium-Promoted Yttria-Zirconia-Supported Ni Catalyst forHydrogen Production via the Dry Reforming of Methane: Role ofBarium in the Phase Stabilization of Cubic ZrO2 br

:developing cost-effective nonprecious active metal-basedcatalysts for syngas (H2/CO) production via the dry reforming of methane(DRM) for industrial applications has remained a challenge. Herein, weutilized a facile and scalable mechanochemical method to develop Ba-promoted (1-5 wt %) zirconia and yttria-zirconia-supported Ni-basedDRM catalysts. BET surface area and porosity measurements, infrared,ultraviolet-visible, and Raman spectroscopy, transmission electronmicroscopy, and temperature-programmed cyclic (reduction-oxidation-reduction) experiments were performed to characterize and elucidate thecatalytic performance of the synthesized materials. Among differentcatalysts tested, the inferior catalytic performance of 5Ni/Zr was attributedto the unstable monoclinic ZrO2support and weakly interacting NiOspecies whereas the 5Ni/YZr system performed better because of the stablecubic ZrO2phase and stronger metal-support interaction. It is establishedthat the addition of Ba to the catalysts improves the oxygen-endowing capacity and stabilization of the cubic ZrO2and BaZrO3phases. Among the Ba-promoted catalysts, owing to the optimal active metal particle size and excess ionic CO32-species, the5Ni4Ba/YZr catalyst demonstrated a high, stable H2yield (i.e., 79% with a 0.94 H2/CO ratio) for up to 7 h of time on stream. The5Ni4Ba/YZr catalyst had the highest H2formation rate, 1.14 mol g-1h-1and lowest apparent activation energy, 20.07 kJ/mol,among all zirconia-supported Ni catalyst systemsISSN:2470-134

Current Overview on Therapeutic Potential of Vitamin D in Inflammatory Lung Diseases

Inflammatory lung disorders (ILDs) are one of the world’s major reasons for fatalities and sickness, impacting millions of individuals of all ages and constituting a severe and pervasive health hazard. Asthma, lung cancer, bronchiectasis, pulmonary fibrosis acute respiratory distress syndrome, and COPD all include inflammation as a significant component. Microbe invasions, as well as the damage and even death of host cells, can cause and sustain inflammation. To counteract the negative consequences of irritants, the airways are equipped with cellular and host defense immunological systems that block the cellular entrance of these irritants or eliminate them from airway regions by triggering the immune system. Failure to activate the host defense system will trigger chronic inflammatory cataracts, leading to permanent lung damage. This damage makes the lungs more susceptible to various respiratory diseases. There are certain restrictions of the available therapy for lung illnesses. Vitamins are nutritional molecules that are required for optimal health but are not produced by the human body. Cholecalciferol (Vitamin D) is classified as a vitamin, although it is a hormone. Vitamin D is thought to perform a function in bone and calcium homeostasis. Recent research has found that vitamin D can perform a variety of cellular processes, including cellular proliferation; differentiation; wound repair; healing; and regulatory systems, such as the immune response, immunological, and inflammation. The actions of vitamin D on inflammatory cells are dissected in this review, as well as their clinical significance in respiratory illnesses

Arabinoxylan-Carboxymethylcellulose composite films for antibiotic delivery to infected wounds

Modern dressings should provide for local delivery of antibiotics and protect the wound from bacterial infection, dehydration and environmental factors to achieve optimal healing. The local delivery of antibiotics can reduce adverse effects and resistance challenges. In this study, we fabricated film dressings composed of arabinoxylan (AX) from Plantago ovata seed husks and carboxymethylcellulose (CMC) by a solvent cast method for the delivery of the antibiotic amikacin (AMK). To determine the suitability of the prepared AX-CMC composite films as wound dressings and drug delivery materials, their physical, chemical, mechanical, morphological, thermal, pharmaceutical, antimicrobial, cytocompatible, and drug delivery properties were investigated. The results demonstrated that the dressings were suitable for delivering the drug at the wound site in a sustained manner and keeping the environment moist for rapid healing. The AMK-loaded AX-CMC films exhibited controlled release of AMK, excellent antibacterial activity, and cytocompatibility. Thus, the AX-CMC composite films appear to be promising bioactive dressing materials for the prevention of wound infections

Repetitive Traumatic Brain Injury Causes Neuroinflammation before Tau Pathology in Adolescent P301S Mice

Repetitive closed head injury (rCHI) is commonly encountered in young athletes engaged in contact and collision sports. Traumatic brain injury (TBI) including rCHI has been reported to be an important risk factor for several tauopathies in studies of adult humans and animals. However, the link between rCHI and the progression of tau pathology in adolescents remains to be elucidated. We evaluated whether rCHI can trigger the initial acceleration of pathological tau in adolescent mice and impact the long-term outcomes post-injury. To this end, we subjected adolescent transgenic mice expressing the P301S tau mutation to mild rCHI and assessed tau hyperphosphorylation, tangle formation, markers of neuroinflammation, and behavioral deficits at 40 days post rCHI. We report that rCHI did not accelerate tau pathology and did not worsen behavioral outcomes compared to control mice. However, rCHI induced cortical and hippocampal microgliosis and corpus callosum astrocytosis in P301S mice by 40 days post-injury. In contrast, we did not find significant microgliosis or astrocytosis after rCHI in age-matched WT mice or sham-injured P301S mice. Our data suggest that neuroinflammation precedes the development of Tau pathology in this rCHI model of adolescent repetitive mild TBI

Repetitive Traumatic Brain Injury Causes Neuroinflammation before Tau Pathology in Adolescent P301S Mice

Repetitive closed head injury (rCHI) is commonly encountered in young athletes engaged in contact and collision sports. Traumatic brain injury (TBI) including rCHI has been reported to be an important risk factor for several tauopathies in studies of adult humans and animals. However, the link between rCHI and the progression of tau pathology in adolescents remains to be elucidated. We evaluated whether rCHI can trigger the initial acceleration of pathological tau in adolescent mice and impact the long-term outcomes post-injury. To this end, we subjected adolescent transgenic mice expressing the P301S tau mutation to mild rCHI and assessed tau hyperphosphorylation, tangle formation, markers of neuroinflammation, and behavioral deficits at 40 days post rCHI. We report that rCHI did not accelerate tau pathology and did not worsen behavioral outcomes compared to control mice. However, rCHI induced cortical and hippocampal microgliosis and corpus callosum astrocytosis in P301S mice by 40 days post-injury. In contrast, we did not find significant microgliosis or astrocytosis after rCHI in age-matched WT mice or sham-injured P301S mice. Our data suggest that neuroinflammation precedes the development of Tau pathology in this rCHI model of adolescent repetitive mild TBI