Protective effect of glucosamine cyclohexyl ester on osteoarthritis in rat via targeting expressions of matrix metalloproteinase and tissue inhibitor of metalloproteinases-1

Purpose: To investigate the therapeutic effect of glucosamine cyclohexyl ester on osteoarthritis (OA) in a rat model.Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assays were used to analyze the effect of glucosamine cyclohexyl ester on changes in mRNA and protein expressions of matrix metalloproteinase and tissue inhibitor of metalloproteinases-1 in isolated rat chondrocytes, and in a rat model of OA. The rat model of OA was prepared by injecting monoiodoacetate to Sprague-Dawley rats via intra-articular route.Results: Treatment of the chondrocytes with glucosamine cyclohexyl ester for 48 h prevented interleukin-1 β (IL-1β)-mediated increases in mRNA and protein  expressions in matrix metalloproteinases-1, -3 and -13, and also blocked IL-1β-induced decreases in mRNA and protein expressions of tissue inhibitor of metalloproteinase-1. Glucosamine cyclohexyl ester treatment also blocked the onset of morphological changes such as irregular surface, adhesion of tissues andpresence of osteophytes in the femoral condyle surface of the OA rats. Mankin score for control, OA and glucosamine cyclohexyl ester treatment groups were 0.98 ± 0.15, 8.35 ± 0.88 and 2.39 ± 0. 67 (p = 0.002), respectively. Treatment of OA rats with glucosamine cyclohexyl ester also inhibited increases in the activities of matrix metalloproteinases-1, -3 and -13, and decreases of tissue inhibitor of metalloproteinase-1 mRNA and protein expressions. Treatment of chondrocytes and OA rats with IL-1β caused no significant changes in the levels of H3K27 and H4K8.Conclusion: These results show that glucosamine cyclohexyl ester prevents OA by targeting the expressions of matrix metalloproteinases-1, -3 and -13 and tissue inhibitor of metalloproteinases-1.Keywords: Metalloproteinases, Interleukin, Mankin score, Osteoarthritis, Cartilag

Flotillin-2 Modulates Fas Signaling Mediated Apoptosis after Hyperoxia in Lung Epithelial Cells

Lipid rafts are subdomains of the cell membrane with distinct protein composition and high concentrations of cholesterol and glycosphingolipids. Raft proteins are thought to mediate diverse cellular processes including signal transduction. However, its cellular mechanisms remain unclear. Caveolin-1 (cav-1, marker protein of caveolae) has been thought as a switchboard between extracellular matrix (ECM) stimuli and intracellular signals. Flotillin-2/reggie-1(Flot-2) is another ubiquitously expressed raft protein which defines non-caveolar raft microdomains (planar raft). Its cellular function is largely uncharacterized. Our novel studies demonstrated that Flot-2, in conjunction with cav-1, played important functions on controlling cell death via regulating Fas pathways. Using Beas2B epithelial cells, we found that in contrast to cav-1, Flot-2 conferred cytoprotection via preventing Fas mediated death-inducing signaling complex (DISC) formation, subsequently suppressed caspase-8 mediated extrinsic apoptosis. Moreover, Flot-2 reduced the mitochondria mediated intrinsic apoptosis by regulating the Bcl-2 family and suppressing cytochrome C release from mitochondria to cytosol. Flot-2 further modulated the common apoptosis pathway and inhibited caspase-3 activation via up-regulating the members in the inhibitor of apoptosis (IAP) family. Last, Flot-2 interacted with cav-1 and limited its expression. Taken together, we found that Flot-2 protected cells from Fas induced apoptosis and counterbalanced the pro-apoptotic effects of cav-1. Thus, Flot-2 played crucial functions in cellular homeostasis and cell survival, suggesting a differential role of individual raft proteins

A bibliometric analysis of studies on the gut microbiota in cardiovascular disease from 2004 to 2022

BackgroundIncreasing evidence indicates that the gut microbiota (GM) is linked to cardiovascular disease (CVD). Many studies on the GM in CVD have been published in the last decade. However, bibliometric analysis in this field is still lacking.MethodsOn 30 September 2022, a search of the Web of Science™ (WoS; Clarivate™, Philadelphia, PA, USA) yielded 1,500 articles and reviews on the GM and CVD. Microsoft Excel and CiteSpace and VOSviewer software were used to analyze publication trends and research hotspots in this field.ResultsOur search generated 1,708 publications on the GM in CVD published between 2004 and 2022, and 1,500 articles and review papers were included in the final analysis. The number of publications relating to the GM in CVD increased from 1 in 2004 to 350 in 2021. China (485 publications, 9,728 non-self-citations, and an H-index of 47) and the USA (418 publications, 24,918 non-self-citations, and an H-index of 82) contributed 32.31%, and 27.85%, respectively, of the total number of publications. Examination of the number of publications (Np) and number of citations, excluding self-citations (Nc), of individual authors showed that Y. L. Tian (Np: 18, Nc: 262, and H-index: 12), from China, is the most productive author, followed by R. Knight (Np: 16, Nc: 3,036, and H-index: 15) and M. Nieuwdorp (Np: 16, Nc: 503, and H-index: 9). The Chinese Academy of Medical Sciences and Peking Union Medical College accounted for the largest number of publications (Np: 62, Nc: 3,727, and H-index: 13, average citation number (ACN): 60.11). The journal Nutrients had the most publications (Np: 73, Nc: 2,036, and ACN: 27.89). The emerging keywords in this field were “monooxygenase 3” (strength 3.24, 2020–2022), “short-chain fatty acid” (strength 4.63, 2021–2022), “fatty liver disease” (strength 3.18, 2021–2022), “metabolic disease” (strength 3.04, 2021–2022), “Mediterranean diet” (strength 2.95, 2021–2022), “prevention” (strength 2.77, 2021–2022), and “intestinal barrier” (strength 2.8, 2021–2022).ConclusionPublications on the GM in CVD rapidly increased in the last decade. The USA was the most influential country in publications in this field, followed by China. The journal with the most publications was Nutrients. Monooxygenase-3, short-chain fatty acids, fatty liver disease, metabolic disease, the Mediterranean diet, intestinal barrier, and prevention are the current hotspots or potential hotspots for future study

An electroporation chip based on flexible microneedle array for in vivo nucleic acid delivery

This paper reports a flexible microneedle array (MNA) electroporation chip for in vivo nucleic acid delivery, which is of great importance for gene therapy. Silicon MNA is proposed to penetrate the high-resistant stratum corneum, while a flexible parylene substrate is used to fit the natural shape of electroporated objects. The chip provides a sufficient electrical field beneath the skin for electroporation with low voltage, which is less likely to harm tissues. Using the proposed chip, we successfully achieved plasmid DNA expression and siRNA delivery in living tissue with low voltage (30-40V). Neither physical nor biological harm to skin was observed. ? 2014 IEEE.EICPCI-S(ISTP)

Addition of a carbene catalyst to indole aryl aldehyde activates a remote δ-sp2 carbon for protonation and formal [4+2] reaction

The addition of a carbene catalyst to an indole aryl aldehyde leads to the activation of a remote sp2 carbon that is five atoms away from the catalyst. The unsaturated Breslow intermediate formed between the catalyst and substrate undergoes an internal redox reaction and remote carbon protonation to generate an analogous azolium vinyl enolate intermediate. Subsequent [4+2] reaction with cyclic imine substrates eventually affords multicyclic pyridoindoles as nearly single diastereomers with excellent enantioselectivities.NRF (Natl Research Foundation, S’pore)ASTAR (Agency for Sci., Tech. and Research, S’pore)MOE (Min. of Education, S’pore)Accepted versio

Molecular Characteristics and Quantitative Proteomic Analysis of <i>Klebsiella pneumoniae</i> Strains with Carbapenem and Colistin Resistance

Carbapenem-resistant Klebsiella pneumoniae (CRKP) are usually multidrug resistant (MDR) and cause serious therapeutic problems. Colistin is a critical last-resort therapeutic option for MDR bacterial infections. However, increasing colistin use has led to the emergence of extensively drug-resistant (XDR) strains, raising a significant challenge for healthcare. In order to gain insight into the antibiotic resistance mechanisms of CRKP and identify potential drug targets, we compared the molecular characteristics and the proteomes among drug-sensitive (DS), MDR, and XDR K. pneumoniae strains. All drug-resistant isolates belonged to ST11, harboring blaKPC and hypervirulent genes. None of the plasmid-encoded mcr genes were detected in the colistin-resistant XDR strains. Through a tandem mass tag (TMT)-labeled proteomic technique, a total of 3531 proteins were identified in the current study. Compared to the DS strains, there were 247 differentially expressed proteins (DEPs) in the MDR strains and 346 DEPs in the XDR strains, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that a majority of the DEPs were involved in various metabolic pathways, which were beneficial to the evolution of drug resistance in K. pneumoniae. In addition, a total of 67 DEPs were identified between the MDR and XDR strains. KEGG enrichment and protein–protein interaction network analysis showed their participation in cationic antimicrobial peptide resistance and two-component systems. In conclusion, our results highlight the emergence of colistin-resistant and hypervirulent CRKP, which is a noticeable superbug. The DEPs identified in our study are of great significance for the exploration of effective control strategies against infections of CRKP

Low-Diffusion Fricke Gel Dosimeters with Core-Shell Structure Based on Spatial Confinement

The diffusion of ferric ions is an important challenge to limit the application of Fricke gel dosimeters in accurate three-dimensional dose verification of modern radiotherapy. In this work, low-diffusion Fricke gel dosimeters, with a core-shell structure based on spatial confinement, were constructed by utilizing microdroplet ultrarapid freezing and coating technology. Polydimethylsiloxane (PDMS), with its excellent hydrophobicity, was coated on the surface of the pellets. The concentration gradient of the ferric ion was realized through shielding half of a Co-60 photon beam field size, and ion diffusion was measured by both ultraviolet-visible spectrophotometry and magnetic resonance imaging. No diffusion occurred between the core-shell pellets, even at 96 h after irradiation, and the diffusion length at the irradiation boundary was limited to the diameter (2–3 mm) of the pellets. Furthermore, Monte Carlo calculations were conducted to study dosimetric properties of the core-shell dosimeter, which indicated that a PDMS shell hardly affected the performance of the dosimeter

Addition of N-heterocyclic carbene catalyst to aryl esters induces remote C-Si bond activation and benzylic carbon functionalization

Through the incorporation of a silicon atom to an aryl carboxylic ester substrate, the resulting C-Si bond can be activated via the addition of a carbene catalyst on a remote site. This strategy allows for efficient functionalization of the benzylic sp3-carbons of aryl carboxylic esters.NRF (Natl Research Foundation, S’pore)ASTAR (Agency for Sci., Tech. and Research, S’pore)MOE (Min. of Education, S’pore)Accepted versio