TNFα inhibitors reduce bone loss in rheumatoid arthritis independent of clinical response by reducing osteoclast precursors and IL-20.

This is a pre-copyedited, author-produced version of an article accepted for publication in Rheumatology following peer review. The version of record:Mohammed Al-Bogami, Jonas Bystrom, Felix Clanchy, Taher E Taher, Pamela Mangat, Richard O Williams, Ali S Jawad, Rizgar A Mageed, TNFα inhibitors reduce bone loss in rheumatoid arthritis independent of clinical response by reducing osteoclast precursors and IL-20, Rheumatology, keaa551, https://doi.org/10.1093/rheumatology/keaa551 is available online at:  https://doi.org/10.1093/rheumatology/keaa551OBJECTIVES: About half of RA patients treated with TNFα inhibitors either do not respond or lose their initial therapeutic response over time. The clinical response is measured by reduction in DAS28, which primarily reflects inflammation. However, other effects of TNFα inhibitors, such as impact on bone erosion, are not assessed by DAS28. We aimed to examine the effect of TNFα inhibitors on bone density, bone biomarkers and cytokine production in responder and non-responder patients and assessed mechanisms of action. METHODS: BMD in the lumbar spine and femur neck of 117 RA patients was measured by DEXA scan. Bone turnover biomarkers CTX, osteoprotegerin (OPG), osteocalcin and RANKL were measured by ELISA. Levels of 16 cytokines in plasma and in tissue culture supernatants of ex vivo T cells were measured by multiplex assays and ELISA. The effect of treatment with TNFα inhibitors on blood mononuclear cell (MNC) differentiation to osteoclast precursors (OCP) was measured flow cytometry and microscopy. RESULTS: TNFα inhibitors improved lumbar spine BMD but had modest effects on blood bone biomarkers, irrespective of patients' clinical response. Blood OCP numbers and the ability of monocytes to differentiate to OCP in vitro declined after treatment. Treatment also reduced RANK expression and IL-20 production. BMD improvement correlated with reduced levels of IL-20 in responder patients. CONCLUSION: This study reveals that TNFα inhibitors reduce lumbar spine bone loss in RA patients irrespective of changes in DAS28. The reduction in bone loss is associated with reduction in IL-20 levels in responder patients

Free-Standing Hierarchically Sandwich-Type Tungsten Disulfide Nanotubes/Graphene Anode for Lithium-Ion Batteries

Transition metal dichalcogenides (TMD), analogue of graphene, could form various dimensionalities. Similar to carbon, one dimensional (1D) nanotube of TMD materials has wide application in hydrogen storage，Li-ion batteries and supercapacitors due to their unique structure and properties. Here we demonstrate the feasibility of tungsten disulfide nanotubes (WS2-NTs)/graphene (GS) sandwich-type architecture as anode for lithium-ion batteries for the first time. The graphene based hierarchical architecture plays vital roles in achieving fast electron/ion transfer, thus leading to good electrochemical performance. When evaluated as anode, WS2-NTs /GS hybrid could maintain a capacity of 318.6 mA/g over 500 cycles at a current density of 1A/g. Besides, the hybrid anode does not require any additional polymetric binder, conductive additives or a separate metal current-collector. The relatively high density of this hybrid is beneficial for high capacity per unit volume. Those characteristics make it a potential anode material for light and high performance lithium-ion batteries

Influence of resveratrol on liver fibrosis induced by dimethylnitrosamine in male rats

Liver fibrosis is a significant health problem which represents the liver’s scarring process and response to injury through deposition of collagen and extracellular matrix, and ultimately leads to cirrhosis. Resveratrol is a naturally occurring phytoalexin found predominantly in grapes. This study aimed to investigate the antifibrotic role of resveratrol on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. Rats were divided into four groups and treated for three weeks; control, resveratrol administered orally (20 mg/kg daily), DMN intraperitoneally injected (10 mg/kg 3 days/week), and the last group was pre-treated daily with resveratrol then injected with DMN, 3 days/week. DMN administration induced severe liver pathological alterations. However, oral administration of resveratrol before DMN significantly prevented the induced loss in body weight, as well as the increase in liver weight which arise from DMN administration. Resveratrol has also inhibited the elevation of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin levels. Furthermore, resveratrol significantly increased hepatic reduced glutathione (GSH) levels and reduced the levels of malondialdehyde (MDA) due to its antioxidants effect as well as increased serum protein levels. In addition, DMN induced elevation in hydroxyproline content. On the other hand, hydroxyproline level was significantly reduced in the resveratrol pretreated rats. Resveratrol has also remarkably maintained the normal liver lobular architecture. Moreover, resveratrol had displayed potent potentials to prevent collagen deposition, lymphocytic infiltration, necrosis, steatosis, vascular damage, blood hypertention, cholangiocyte proliferation. It can be concluded that resveratrol has a marked protective role on DMN-induced liver fibrosis in rats, and can be considered as antiproliferative, antihypertensive, as well as antifibrotic agent and may be used to block the development of liver fibrosis. Keywords: Dimethylnitrosamine, Liver fibrosis, Resveratrol, Antifibrotic role, Rat

Cubic–Quartic Optical Soliton Perturbation with Differential Group Delay for the Lakshmanan–Porsezian–Daniel Model by Lie Symmetry

This paper employs Lie symmetry analysis to recover cubic–quartic optical soliton solutions to the Lakshmanan–Porsezian–Daniel model in birefringent fibers. The results are a sequel to the previously reported work on the same model in unpolarized fibers. Dark, singular, and straddled optical solitons that emerged from the scheme are presented

Cubic–Quartic Optical Soliton Perturbation with Differential Group Delay for the Lakshmanan–Porsezian–Daniel Model by Lie Symmetry

This paper employs Lie symmetry analysis to recover cubic–quartic optical soliton solutions to the Lakshmanan–Porsezian–Daniel model in birefringent fibers. The results are a sequel to the previously reported work on the same model in unpolarized fibers. Dark, singular, and straddled optical solitons that emerged from the scheme are presented

Efficacy of Prednisolone/Zn Metal Complex and Artemisinin Either Alone or in Combination on Lung Functions after Excessive Exposure to Electronic Cigarettes Aerosol with Assessment of Antibacterial Activity

The use of transition metal complexes as therapeutic compounds has become more and more pronounced. These complexes offer a great diversity of uses in their medicinal applications. Electronic cigarettes (ECs) are an electronic nicotine delivery system that contain aerosol (ECR). The ligation behavior of prednisolone, which is a synthetic steroid that is used to treat allergic diseases and asthma arthritis, and its Zn (II) metal complex were studied and characterized based on elemental analysis, molar conductance, Fourier-transform infrared (FT-IR) spectra, electronic spectra, XRD, scanning electron microscopy (SEM), energy dispersive x-ray (EDX), and transmission electron microscopy (TEM). The FT-IR spectral data revealed that PRD acts as a mono-dentate ligand via oxygen atoms of the carbonyl group. Electronic and FT-IR data revealed that the PRD/Zn (II) metal complexes have square planner geometry. Artemisinin (ART) is the active main constituent of Artemisia annua extract, and it has been demonstrated to exert an excellent antimalarial effect. The experiment was performed on 40 male mice that were divided into the following 7 groups: Control, EC group, PRD/Zn, ART, EC plus PRD/Zn, EC plus ART, and PRD plus combination of PRD/Zn and ART. Serum CRP, IL-6, and antioxidants biomarkers were determined. Pulmonary tissue histology was evaluated. When in combination with Zn administration, PRD showed potent protective effects against pulmonary biochemical alterations induced by ECR and suppressed severe oxidative stress and pulmonary structure alterations. Additionally, PRD/Zn combined with ART prevented any stress on the pulmonary tissues via antioxidant regulation, reducing inflammatory markers CRP and Il-6 and improving antioxidant enzymatic levels more than either PRD or ART alone. Therefore, PRD/Zn combined with ART produced a synergistic effect against any sort of oxidative stress and also improved the histological structure of the lung tissues. These findings are of great importance for saving pulmonary function, especially during pandemic diseases, such as during the COVID-19 pandemic