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Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation and swelling. Several studies have demonstrated that RA fibroblast-like synovial cells (RA-FLS) play an important role in RA pathogenesis. Activated RA-FLS contribute to synovial inflammation by secreting inflammatory cytokines including interleukin (IL)-1β, IL-6 and tumor necrosis factor-α. LMT-28 is derivative of oxazolidone and exerts anti-inflammatory effects on RA via IL-6 signaling pathway regulation. LMT-28 also regulates T cell differentiation in RA condition. However, the effect of LMT-28 on the migration and invasion of RA-FLS remains unknown. Kaempferol has been reported to have pharmacological effects on various diseases, such as inflammatory diseases, autoimmune diseases, and cancer. Additionally, kaempferol has been reported to inhibit RA-FLS migration and invasion, but it is not known about the therapeutic mechanism including molecular mechanism such as receptor. The present study aimed to investigate the synergistic effects of the combined treatment of LMT-28 and kaempferol on RA-FLS activation and RA pathogenesis in mouse model. LMT-28 and kaempferol co-administration inhibited RA disease severity and histological collapse in the joint tissues of CIA mice, as well as downregulated the levels of pro-inflammatory cytokines in mouse serum. Additionally, the combined treatment inhibited excessive differentiation of T helper 17 cells and osteoclasts. Furthermore, compared with single treatments, combined treatment showed enhanced inhibitory effects on the hyperactivation of IL-6-induced signaling pathway in RA-FLS. Combined treatment also inhibited RA-FLS cell proliferation, migration, and invasion and suppressed the expression of matrix metalloproteinase in RA-FLS. Furthermore, we confirmed that the combined treatment inhibited chondrocyte proliferation, migration, and invasion. In conclusion, our results suggest that the combined treatment of LMT-28 and kaempferol exerts a synergistic effect on the RA development via the regulation of IL-6-induced hyperactivation of RA-FLS. Furthermore, this study suggests that combination therapies can be an effective therapeutic option for arthritis. [ABSTRACT FROM AUTHOR]

Summary: Molybdenum sulfide (MoSx)‐based materials have been extensively studied as a potential alternative of low‐capacity graphite anode, owing to their remarkable capacity through intercalation and conversion reactions. However, these materials should be electrochemically activated at a low potential in first discharge and simultaneously degrade, owing to their inert basal plane and unstable sulfur configuration, respectively, leading to unexpectedly low performance. Hence, it is necessary to apply sulfur‐enriched crystalline Mo3S13 clusters as an anode material to increase the number of active sites and energy densities. Unlike MoS2 possessing only terminal sulfur, Mo3S13 clusters have higher sulfur content with various and stable configuration in their structure, which can act as additional active sulfur sites. To realize an electrode with high energy density, we used the Mo3S13 clusters without any carbon supports as active materials. In the electrode preparation, we confirmed that employing poly(acrylic acid) and isopropyl alcohol as a binder and solvent, respectively, was appropriate for retaining the cluster crystallinity, resulting in the enhanced cycling stability. The Mo3S13 cluster‐based electrode as a carbon‐free electrode exhibited capacity of 1192 mAh g−1 at 0.1 A g−1 and good C‐rate capability. The significant capacity variation with the selective removal of sulfur configuration in Mo3S13 clusters indicates that the increased sulfur contents were provided as additional sources for (de)lithiation. [ABSTRACT FROM AUTHOR]

The major surface protein (MspTL) of Treponema lecithinolyticum, associated with periodontitis and endodontic infections, has been reported to induce proinflammatory mediators such as intercellular adhesion molecule (ICAM)-1, and interleukin (IL)-1[beta], IL-6 and IL-8. The purpose of this study was to examine the role of MspTL in cell adhesion/migration and to identify its proinflammatory domains. Using the human monocytic cell line THP-1 and human dermal microvascular endothelial cells (HMEC-1), it was demonstrated that MspTL increased adhesion of monocytes to endothelial cells and transendothelial migration. To analyse the proinflammatory domains of the protein, four gene constructs covering different regions of MspTL were designed and expressed in Escherichia coli using the expression vector pQE-30. Histidine-tagged recombinant proteins were purified using Ni-NTA agarose and polymyxin B agarose to remove LPS contamination. Recombinant truncated polypeptides were assessed for the ability to induce ICAM-1 and proinflammatory factors in THP-1 cells by real-time RT-PCR and ELISA. Of the four polypeptides, the one spanning the N-terminal 86 amino acids significantly induced ICAM-1, IL-1[beta], IL-6, IL-8, tumour necrosis factor-[alpha] (TNF-[alpha]), cyclooxygenase (COX)-2, and prostaglandin [E.sub.2] ([PGE.sub.2]). The results indicate that MspTL may induce cell adhesion and inflammation via its N-terminal region.

Summary: Applications utilizing Li‐ion batteries (LIBs) have recently been broadened from portable electronic devices to electric vehicles. Graphite has been applied as an anode material for commercialized LIBs; however, there is a growing demand for application‐oriented LIBs with higher energy and power densities, and faster charging, compared with its limited electrochemical properties. Heteroatom‐doped graphene has been considered as a potential alternative to graphite, although its synthesis is complex and costly. In this study, we introduced a facile strategy to realize advanced anode materials through fine control of the sheet size and oxygen‐containing functional groups on the surface of graphene oxide (GO) as a raw material for heteroatom‐doped graphene. The sheet size of GO is inversely proportional to the amount of oxidizing agent, which affects the formation of various types of oxygen‐containing functional groups at the edges of GO. Mild annealing of GO selectively removes the functional groups with weak binding strength, leading to the formation of GO maximized with carbonyl groups, which can interact with Li ions quickly and reversibly. The GO with the average sheet size of 500 nm developed in this study exhibits capacities of up to 779 and 220 mAh g−1 at 0.1 and 2 A g−1, respectively. Therefore, decreasing the sheet size of GO with mild‐temperature annealing increases the number of carbonyl groups formed on the additional exposed edge of the sheets, resulting in facile Li‐ion interaction and a higher capacity as an anode material. [ABSTRACT FROM AUTHOR]

Summary: Lithium‐ion batteries (LIBs) have been widely used for powering electric vehicles (EVs), however, the charging time of LIBs is considerably higher than the refueling time of petrol‐fueled vehicles, which limits the applications of LIBs. Materials that can overcome this limitation should be developed, and these materials should be inexpensive to commercialize. In this study, activated carbon (AC) was used as an anode material in LIB to satisfy both the requirements. The surface and pore structure of commercial AC was suitably modified for fast charging using physical and chemical activation methods, that is, P‐AC and C‐AC, respectively. We focused on the stability of various kinds of electrode materials, such as AC, C‐AC, P‐AC, commercial graphite, and graphene, under fast‐charging conditions. Among these methods, P‐AC exhibited the most stable and highest capacity during 500 cycles at the 5C rate, although the initial capacity (<50 cycles) of P‐AC was given the second priority. We believe that the suitable mixture of meso‐ and micropores in P‐ACs increases the diffusivity and insertion rate of the Li‐ion (solvation) at fast‐charging condition, thereby leading to higher long‐term stability. [ABSTRACT FROM AUTHOR]

Objectives: The interleukin-6 (IL-6)-mediated signaling pathway plays an essential role in the development of rheumatoid arthritis. LMT-28 suppresses the activation of the IL-6-mediated signaling by direct targeting of gp130. Although LMT-28 and metformin both possess anti-inflammatory activity, the beneficial effect of LMT-28 and metformin combination on a collagen-induced arthritis (CIA) model has not yet been investigated. This study aimed to investigate the anti-inflammatory effect and mechanism of a combination of LMT-28 and metformin in a CIA model. Methods: In MH7A cells, cell proliferation and the IL-6-mediated signaling pathway following administration of LMT-28 and metformin combination was analyzed through MTT assay and Western blotting. The level of T helper 17 (Th17) cell differentiation from CD4+ T cells was analyzed in mouse splenocytes and human peripheral blood mononuclear cells. Arthritis score, incidence rate, inflammatory cytokine, and T-cell subsets were measured in CIA mice following administration of LMT-28 and metformin combination. Results: Combination treatment with LMT-28 and metformin diminished proliferation of MH7A cells and IL-6-mediated gp130, STAT3, and ERK signaling more than in individual treatments. Furthermore, the differentiation of CD4+ T cells into Th17 cells was attenuated more by combination treatment with LMT-28 and metformin than individual treatments. The combination of LMT-28 and metformin ameliorated the arthritic score better than individual treatments. The combination significantly reduced tumor necrosis factor and IL-6 levels in the sera and had an anti-inflammatory effect on the distribution of Treg/Th17 cells in the lymph nodes. Conclusion: Combination treatment with LMT-28 and metformin significantly ameliorates arthritic symptoms in CIA by suppressing Th17 differentiation and IL-6 signaling. [ABSTRACT FROM AUTHOR]

Antiplatelet drugs are conventionally used as treatments because of their anti‐coagulation functions. However, their pleiotropic effects are of great significance to the treatment of ischaemic cardiovascular diseases. Many studies have reported that an excessive amount of inflammation driven by tumour necrosis factor (TNF) is closely related to the prevalence of atherosclerosis. As the drug selection criteria and evaluation methods related to the anti‐TNF activity of antiplatelet drugs remain limited, our investigation of these drugs should prove beneficial. In this study, we compared the anti‐TNF activity of three antiplatelet agents, namely clopidogrel, sarpogrelate, and cilostazol, using the TNF‐induced inflammatory mouse model. After the oral administration of these drugs, acute inflammation was induced via injection of lipopolysaccharide (LPS) or D‐galactosamine (D‐gal) and TNF. Serum TNF levels, and the mRNA and protein expression levels of TNF in mouse heart tissue, macrophage accumulation in aortic lesions, and mouse survival were analysed to compare the anti‐TNF effects of the three antiplatelet agents. Of the three antiplatelet agents, cilostazol significantly reduced the different levels under the most effective observation. In addition, cilostazol was found to attenuate the TNF‐stimulated phosphorylation of mitogen‐activated protein kinase (MAPK) and nuclear factor kappa‐light‐chain‐enhancer of activated B cell (NF‐κB) p65 in the aortic vascular smooth muscle cell line, MOVAS‐1 and the D‐gal plus TNF‐challenged heart tissue of mouse. Therefore, cilostazol is the most ideal of the three antiplatelet drugs for the treatment of TNF‐mediated inflammatory disorders. [ABSTRACT FROM AUTHOR]