Phosphorus-Doped Activated Coconut Shell Carbon-Anchored Highly Dispersed Pt for the Chemoselective Hydrogenation of Nitrobenzene to p-Aminophenol.

Highly dispersed Pt nanoparticles (∼2.5 nm) on phosphorus-doped activated coconut shell carbon (Pt/P-ACC) were synthesized by a two-step impregnation route. Pt/P-ACC showed a high activity, chemoselectivity, and reusability toward the hydrogenation of nitrobenzene to p-aminophenol, with hydrogen as the reducing agent in sulfuric acid. The effects of P species on the catalyst structure, surface properties, and catalytic performance were investigated. It was found that the Pt/P-ACC catalyst had an excellent catalytic activity due to its smaller Pt nanoparticles and higher content of surface-active metal compared with Pt/ACC. Besides, the experimental results and in situ infrared studies demonstrated that the interaction effect between the Pt and P species imbued the surface of Pt with an electron-rich feature, which decreased the adsorption of electron-rich substrates (that is, phenylhydroxylamine) and prevented their full hydrogenation, leading to enhanced selectivity during the hydrogenation of nitrobenzene to p-aminophenol.

One-Pot Synthesis of Al-P-O Catalysts and Their Catalytic Properties for O-Methylation of Catechol and Methanol.

A series of Al-P-O catalysts (Al-xP-O) were prepared using a P123-assisted one-pot method at different P/Al molar ratios and used for O-methylation of catechol and methanol. The influences of the P/Al molar ratio and P123 addition on catalyst structure and surface acid-base characteristics were investigated in detail. Increasing the P/Al molar ratio more favored crystalline aluminophosphate. The P123-assisted Al3+ and PO43- are known to be stabilized through weak steric force so that the formation of crystalline aluminophosphate could be inhibited at higher P/Al molar ratios. The results showed that the prepared Al-P-O catalysts possessed appropriate weak acid and weak base sites, which was beneficial to the reaction of catechol and methanol. The Al-1.1P-O catalyst synthesized with the assistance of P123 exhibited superior catalytic performances, with 52.5% catechol conversion and higher guaiacol selectivity of 97.6%.

Exosomal miR-9-5p secreted by bone marrow-derived mesenchymal stem cells alleviates osteoarthritis by inhibiting syndecan-1.

Mesenchymal stem cells (MSCs) have been demonstrated to serve as targets for the treatment of osteoarthritis (OA) and exosomes derived from MSCs also display chondroprotective effects. This study aims to investigate the regulatory role of exosomal microRNA-9-5p (miR-9-5p) secreted by bone marrow-derived MSCs (BM-MSCs) on OA in a rat model induced by anterior cruciate ligament/medial collateral ligament transection. Luciferase reporter assay was conducted to verify the putative miR-9-5p binding sites to 3'UTR of syndecan-1 (SDC1). Additionally, an intra-articular injection of miR-9-5p carried by BM-MSC-derived exosomes or liposomes into rats with OA-like damage was performed to ascertain the role of exosomal miR-9-5p and a gain-of-function study of SDC1 was carried out to explore the potential mechanism in relation to SDC1. Subsequently, the expression of SDC1 was determined and the levels of inflammatory factors (IL-1, IL-6, TNF-α and CRP) and oxidative stress injury indicators (NO, MDA, iNOS, COX2 and SOD), the contents of AKP as well as the levels of OA-related factors (MMP-13, COMP and OCN) were measured. Injection of miR-9-5p-contained exosomes resulted in an alleviation of inflammation and OA-like damage, which was evidenced by downregulated levels of inflammatory factors, reduced oxidative stress injury and decreased OCN, MMP-13, COMP and AKP levels. As a target gene of miR-9-5p, the upregulation of SDC1 led to aggravation of inflammation and OA-like damage, which is opposite to exosomal miR-9-5p. To conclude, these findings suggest the anti-inflammatory and chondroprotective effects of BM-MSC-derived exosomal miR-9-5p on OA via regulation of SDC1.

Human bone mesenchymal stem cells-derived exosomes overexpressing microRNA-26a-5p alleviate osteoarthritis via down-regulation of PTGS2.

Osteoarthritis (OA) is a degenerative disease characterized by synovium inflammation and articular cartilage damage. The aberrant expression profile of microRNAs (miRNAs) has been implicated in the cartilage of patients with OA. However, how microRNAs carried by exosomes derived from mesenchymal stem cells (MSCs) associated with OA progression is still unknown. Thus, the current study aimed to elucidate the potential therapeutic role of human bone MSC (hBMSC)-derived exosomal miR-26a-5p in OA progression. Initially, the differentially expressed genes related to OA were identified by microarray analysis which provided data predicting the interaction between miR-26a-5p and PTGS2 in OA. Next, miR-26a-5p and PTGS2 were elevated or silenced to determine their effects on the damage of synovial fibroblasts treated with IL-1ß. Exosomes derived from hBMSCs were co-cultured with synovial fibroblasts to explore the effect of hBMSC-derived exosomes carrying miR-26a-5p on synovial fibroblast damage. This effect was further verified by an in vivo experiment. Our results revealed that miR-26a-5p was poorly expressed, while PTGS2 was highly expressed in OA patients and synovial fibroblasts treated with IL-1ß. Furthermore, miR-26a-5p was identified to specifically target PTGS2. Additionally, the overexpression of miR-26a-5p exerted an alleviatory effect on the damage of the synovial fibroblasts by repressing PTGS2. Moreover, hBMSC-derived exosomes overexpressing miR-26a-5p retarded damage of synovial fibroblasts in vitro and alleviated OA damage in vivo. Taken together, hBMSC-derived exosomes overexpressing miR-26a-5p serve as a repressor for damage of synovial fibroblasts via PTGS2 in OA, which is of significance for the treatment of OA in rats.

Different epidermal growth factor receptor signaling pathways in neurons and astrocytes activated by extracellular matrix after spinal cord injury.

Spinal cord injury (SCI) is a serious central nervous system (CNS) trauma that results in permanent and severe disability. The extracellular matrix (ECM) can affect the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) by interacting with the ERK integrin subunits. In this study, we built a model of SCI with glial fibrillary acidic protein-green fluorescent protein (GFAP-GFP) and thymus cell antigen 1-yellow fluorescent protein-H (Thy1-YFPH) in mice that express specific transgenes in their astrocytes or neurons. Then, we collected spinal cord neurons or astrocytes by fluorescence-activated cell sorting (FACS). In this way, we investigated the SCI-induced phosphorylation of ERK1/2 and epidermal growth factor receptor (EGFR) in neurons and astrocytes, and we discovered that the SCI-induced EGFR signaling pathways differed between neurons and astrocytes. In the present study, we found that the Src-dependent phosphorylation of EGFR induced by SCI occurred only in neurons, not in astrocytes. This phenomenon may be due to the involvement of Thy-1, which promoted the binding between Src and EGFR in neurons after SCI. In addition, the expression of the integrin subunits after SCI differed between neurons and astrocytes. Our present study shows that the EGFR signaling pathway triggered by SCI in neurons differed from the EGFR signaling pathway triggered in astrocytes, a finding that may help to pave the way for clinical trials of therapies that inhibit EGFR signaling pathways after SCI.

Protective effect of leptin-mediated caveolin-1 expression on neurons after spinal cord injury.

Spinal cord injury (SCI) causes long-term disability and has no effective clinical treatment. After SCI, extracellular adenosine triphosphate (ATP) leads to an influx of extracellular Ca2+, and this Ca2+ overload causes neuronal toxicosis and apoptosis. The biological functions of leptin have been widely investigated in the central nervous system. In this study, we discovered that the administration of leptin could improve locomotor recovery following SCI. The aim of this study was to determine the neuroprotective mechanism of leptin in vivo and in vitro. The neuronal apoptosis and Ca2+ imaging signal induced by ATP were suppressed by leptin, due to elevated caveolin-1 expression. In vivo two-photon observations revealed that leptin reduced the neuronal Ca2+ imaging signal in the exposed spinal cords of live Thy1-YFP mice. In conclusion, leptin promotes locomotor functional recovery and suppresses neuronal impairment after SCI, suggesting that leptin has a promising clinical therapeutic value for treatment of SCI.

Lithium Inhibits GSK3ß Activity via Two Different Signaling Pathways in Neurons After Spinal Cord Injury.

Spinal cord injury (SCI) is a type of long-term disability with a high morbidity rate in clinical settings for which there is no effective clinical treatment to date. Usually, lithium is used as a popular mood stabilizer. Recently, growing evidence has shown that lithium has clear neuroprotective effects after SCI, and the administration of lithium can effectively improve locomotor recovery. However, the exact neuroprotective mechanism of lithium is still not understood. Glycogen synthase kinase-3 beta (GSK3ß) is a serine/threonine kinase that plays an important role in the neuroprotective effects of lithium both in vivo and in vitro. In this study, we discovered that lithium inhibits GSK3ß activity through two different signaling pathways in spinal cord neurons. In the acute phase, lithium inhibited GSK3ß activity by stimulating phosphorylation of AKT; in the chronic phase, we first discovered that lithium additionally upregulated the expression of Na+, K+-ATPase α1 (NKA α1), which had an inhibitory effect on GSK3ß activity by inducing the expression of glucocorticoid inducible kinase 1 (SGK1). SGK1 is well known as a regulator of the GSK3ß/ß-catenin signaling pathway. Moreover, the suppressed activity of GSK3ß increased the level of ß-catenin in the cytoplasm, which gave rise to the translocation of the freely stabilized ß-catenin to the nucleus. In addition, the accumulation of ß-catenin in the nucleus had the benefits of neuronal survival. Hopefully our findings from this study are beneficial in revealing the neuroprotective mechanism of lithium and in offering novel targets for the development of new SCI therapeutic drugs.

The ameliorative effect of fluoxetine on neuroinflammation induced by sleep deprivation.

It is well known that sleep disorders are harmful to people's health and performance, and growing evidence suggests that sleep deprivation (SD) can trigger neuroinflammation in the brain. The nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome is reported to be relevant to the neuroinflammation induced by SD, but the regulatory signaling that governs the NLRP3 inflammasome in SD is still unknown. Meanwhile, whether the regulatory action of antidepressants in astrocytes could affect the neuroinflammation induced by SD also remains obscure. In this study, we were the first to discover that the antidepressant fluoxetine, a type of specific serotonin reuptake inhibitor widely used in clinical practice, could suppress the neuroinflammation and neuronal apoptosis induced by SD. The main findings from this study are as follows: (i) SD stimulated the expression of activated NLRP3 inflammasomes and the maturation of IL-1ß/18 via suppressing the phosphorylation of STAT3 in astrocytes; (ii) SD decreased the activation of AKT and stimulated the phosphorylation of GSK-3ß, which inhibited the phosphorylation of STAT3; (iii) the NLRP3 inflammasome expression stimulated by SD was partly mediated by the P2X7 receptor; (iv) an agonist of STAT3 could significantly abolish the expression of NLRP3 inflammasomes induced by an agonist of the P2X7 receptor in primary cultured astrocytes; (v) the administration of fluoxetine could reverse the stimulation of NLRP3 inflammasome expression and function by SD through elevating the activation of STAT3. In conclusion, our present research suggests the promising possibility that fluoxetine could ameliorate the neuronal impairment induced by SD.