Inhibitory Effects of Rhaponticin on Osteoclast Formation and Resorption by Targeting RANKL-Induced NFATc1 and ROS Activity

The extravagant osteoclast formation and resorption is the main cause of osteoporosis. Inhibiting the hyperactive osteoclastic resorption is considered as an efficient treatment for osteoporosis. Rhaponticin (RH) is a small molecule that has been reported to possess anti-inflammatory, anti-allergic, anti-fibrotic, and anti-diabetic activities. However, the influence of RH on osteoclasts differentiation and function is still unclear. To this end, an array of assays including receptor activator of nuclear factor kappa-Β (NF-κB) ligand (RANKL) induced osteoclastogenesis, tartrate-resistant acidic phosphatase (TRAcP) staining, immunofluorescence, and hydroxyapatite resorption were performed in this study. It was found that RH had significant anti-catabolic effects by inhibiting osteoclastogenesis and bone resorption without cytotoxicity. Mechanistically, the expression of NADPH oxidase 1 (Nox1) was found to be suppressed and antioxidant enzymes including catalase, superoxide dismutase 2 (SOD-2), and heme oxygenase-1(HO-1) were enhanced following RH treatment, suggesting RH exhibited antioxidant activity by reducing the generation of reactive oxygen species (ROS) as well as enhancing the depletion of ROS. In addition, MAPKs, NF-κB, and intracellular Ca2+ oscillation pathways were significantly inhibited by RH. These changes led to the deactivation of osteoclast master transcriptional factor-nuclear factor of activated T cells 1 (NFATc1), as examined by qPCR and Western blot assay, which led to the decreased expression of downstream integrin β3, c-Fos, cathepsin K, and Atp6v0d2. These results suggested that RH could effectively suppress RANKL-regulated osteoclast formation and bone resorption. Therefore, we propose that RH can represent a novel natural small molecule for the treatment of osteoporosis by inhibiting excessive osteoclast activity

Facile synthesis of N-acetylglycine from chitin-derived N-acetylmonoethanolamine

The effective conversion of renewable chitin and its derivatives to organonitrogen chemicals is of significance. N-acetylmonoethanolamine (NMEA) is a compound that can be produced from N-acetylglucosamine (NAG, the monomer of chitin) via successive retro-aldol and hydrogenation reactions. Here we report the aerobic oxidation of NMEA to N-acetylglycine in O2 using cheap Fe(NO3)3⋅9H2O, TEMPO, and KCl. The effects of catalysts, additives, and reaction conditions on the N-acetylglycine synthesis were investigated. Under optimized conditions, a 62.1% yield of N-acetylglycine with almost full conversion was obtained

Recent advances in catalytic synthesis of 2,5-furandimethanol from 5-hydroxymethylfurfural and carbohydrates

Abstract 5-Hydroxymethylfurfural (HMF) is a versatile platform chemical derived from the dehydration of renewable carbohydrates (typically glucose/fructose-based monosaccharides, oligosaccharides, and polysaccharides). Some useful compounds, such as 2,5-furandimethanol (FDM), 2,5-dimethylfuran (DMF) and 2,5-dimethyltetrahydrofuran (DMTHF), have been synthesized by reduction of HMF. Among these, FDM is a promising diol and can be further converted towards fine chemicals, liquid fuels and polymer materials. In this review, some typical catalytic systems for the synthesis of FDM from both HMF and carbohydrates were summarized. The discussion focused on controlling the reaction networks for the reduction of HMF. The reaction mechanisms and the stability of the catalysts were introduced briefly. Last but not least, the prospects of effective production of FDM were discussed as well

Progress in Catalytic Conversion of Renewable Chitin Biomass to Furan-Derived Platform Compounds

Chitin is one of the most abundant biopolymers on Earth but under-utilized. The effective conversion of chitin biomass to useful chemicals is a promising strategy to make full use of chitin. Among chitin-derived compounds, some furan derivatives, typically 5-hydroxymethylfurfural and 3-acetamido-5-acetylfuran, have shown great potential as platform compounds in future industries. In this review, different catalytic systems for the synthesis of nitrogen-free 5-hydroxymethylfurfural and nitrogen-containing 3-acetamido-5-acetylfuran from chitin or its derivatives are summarized comparatively. Some efficient technologies for enhancing chitin biomass conversion have been introduced. Last but not least, future challenges are discussed to enable the production of valuable compounds from chitin biomass via greener processes

Global Single-Cell Sequencing Landscape of Adipose Tissue of Different Anatomical Site Origin in Humans

Chronic refractory wounds (CRW) are one of the most serious clinical challenges for surgeons to address. Stromal vascular fraction gels (SVFG), including human adipose stem cells (hASCs), have excellent vascular regenerative and tissue repair properties. Here, we combined single-cell RNA sequencing (scRNA-seq) of leg subcutaneous adipose tissue samples with scRNA-seq data from abdominal subcutaneous adipose tissue, leg subcutaneous adipose tissue, and visceral adipose tissue samples from public databases. The results showed specific differences in cellular levels in adipose tissue from different anatomical site sources. We identified cells including CD4+ T cells, hASCs, adipocyte (APC), epithelial (Ep) cells, and preadipocyte. In particular, the dynamics between groups of hASCs, epithelial cells, APCs, and precursor cells in adipose tissue of different anatomical site origins were more significant. Furthermore, our analysis reveals alterations at the cellular level and molecular level, as well as the biological signaling pathways involved in these subpopulations of cells with specific alterations. In particular, certain subpopulations of hASCs have higher cell stemness, which may be related to lipogenic differentiation capacity and may be beneficial in promoting CRW treatment and healing. In general, our study captures a human single-cell transcriptome profile across adipose depots, the cell type identification and analysis of which may help dissect the function and role of cells with specific alterations present in adipose tissue and may provide new ideas and approaches for the treatment of CRW in the clinical setting

TAZ encodes tafazzin, a transacylase essential for cardiolipin formation and central to the etiology of Barth syndrome

Tafazzin, which is encoded by the TAZ gene, catalyzes transacylation to form mature cardiolipin and shows preference for the transfer of a linoleic acid (LA) group from phosphatidylcholine (PC) to monolysocardiolipin (MLCL) with influence from mitochondrial membrane curvature. The protein contains domains and motifs involved in targeting, anchoring, and an active site for transacylase activity. Tafazzin activity affects many aspects of mitochondrial structure and function, including that of the electron transport chain, fission-fusion, as well as apoptotic signaling. TAZ mutations are implicated in Barth syndrome, an underdiagnosed and devastating disease that primarily affects male pediatric patients with a broad spectrum of disease pathologies that impact the cardiovascular, neuromuscular, metabolic, and hematologic systems

Autologous hematopoietic stem cell transplantation following high dose chemotherapy for non-rhabdomyosarcoma soft tissue sarcomas

© 2013 The Cochrane Collaboration. Background: Soft tissue sarcomas (STS) are a highly heterogeneous group of rare malignant solid tumors. Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) comprise all STS except rhabdomyosarcoma. In patients with advanced local or metastatic disease, autologous hematopoietic stem cell transplantation (HSCT) applied after high-dose chemotherapy (HDCT) is a planned rescue therapy for HDCT-related severe hematologic toxicity. The rationale for this update is to determine whether any randomized controlled trials (RCTs) have been conducted and to clarify whether HDCT followed by autologous HSCT has a survival advantage. Objectives: To assess the effectiveness and safety of HDCT followed by autologous HSCT for all stages of non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) in children and adults. Search methods: For this update we modified the search strategy to improve the precision and reduce the number of irrelevant hits. All studies included in the original review were considered for re-evaluation in the update. We searched the electronic databases CENTRAL (2012, Issue 11) in The Cochrane Library, MEDLINE and EMBASE (05 December 2012) from their inception using the newly developed search strategy. Online trials registers and reference lists of systematic reviews were searched. Selection criteria: Terms representing STS and autologous HSCT were required in the title or abstract. In studies with aggregated data, participants with NRSTS and autologous HSCT had to constitute at least 80% of the data. Single-arm studies were included in addition to studies with a control arm because the number of comparative studies was expected to be very low. Data collection and analysis: Two review authors independently extracted study data. Some studies identified in the original review were re-examined and found not to meet the inclusion criteria and were excluded in this update. For studies with no comparator group, we synthesized the results for studies reporting aggregate data and conducted a pooled analysis of individual participant data using the Kaplan-Meyer method. The primary outcomes were overall survival (OS) and treatment-related mortality (TRM). Main results: The selection process was carried out from the start of the search dates for the update. We included 57 studies, from 260 full text articles screened, reporting on 275 participants that were allocated to HDCT followed by autologous HSCT. All studies were not comparable due to various subtypes. We identified a single comparative study, an RCT comparing HDCT followed by autologous HSCT versus standard chemotherapy (SDCT). The overall survival (OS) at three years was 32.7% versus 49.4% with a hazard ratio (HR) of 1.26 (95% confidence interval (CI) 0.70 to 2.29, P value 0.44) and thus not significantly different between the treatment groups. In a subgroup of patients that had a complete response before treatment, OS was higher in both treatment groups and OS at three years was 42.8% versus 83.9% with a HR of 2.92 (95% CI 1.1 to 7.6, P value 0.028) and thus was statistically significantly better in the SDCT group. We did not identify any other comparative studies. We included six single-arm studies reporting aggregate data of cases; three reported the OS at two years as 20%, 48%, and 51.4%. One other study reported the OS at three years as 40% and one further study reported a median OS of 13 months (range 3 to 19 months). In two of the single-arm studies with aggregate data, subgroup analysis showed a better OS in patients with versus without a complete response before treatment. In a survival analysis of pooled individual data of 80 participants, OS at two years was estimated as 50.6% (95% CI 38.7 to 62.5) and at three years as 36.7% (95% CI 24.4 to 49.0). Data on TRM, secondary neoplasia and severe toxicity grade 3 to 4 after transplantation were sparse. The one included RCT had a low risk of bias and the remaining 56 studies had a high risk of bias. Authors' conclusions: A single RCT with a low risk of bias shows that OS after HDCT followed by autologous HSCT is not statistically significantly different from standard-dose chemotherapy. Therefore, HDCT followed by autologous HSCT for patients with NRSTS may not improve the survival of patients and should only be used within controlled trials if ever considered