Anti-arthritic Effect of the Spirocyclopiperazinium Salt Compound  LXM-15 in Rats and Its Underlying Mechanism

In this study, we aimed to evaluate the effects of the spirocyclopiperazinium salt compound LXM-15 on rheumatoid arthritis induced by complete Freund ’s adjuvant (CFA) in rats and investigate the underlying mechanism. The results showed that LXM-15 significantly inhibited the paw edema and ankle swelling, and alleviated the mechanical allodynia and thermal hyperalgesia responses in the CFA rats. The histopathological results revealed that LXM-1 5 ameliorated the infiltration of inflammatory cells and joint destruction. The micro-CT scan showed that LXM-15 alleviated bone erosion and increased BMD in the ankle joints of the CFA rats. Western blot analyses showed that LXM-15 significantly reduced the upregulation of phospho-JAK2, phospho-STA T3, phospho-IκBα, and phospho-NF-κBp65, and the overexpression of BDNF in the dorsal root ganglions. ELISA result showed that the protein level of TNF-α in the paw tissue was decreased upon LXM-15 treatment. RT-PCR analysis showed that the mRNA expression levels of c-fos and BDNF were reduced in the dorsal root ganglions by LXM-15 treatment. The LXM-15-mediated anti-arthritic effects were abolished by treatment with hexamethonium (a peripheral nicotinic receptor antagonist), atropine methylnitrate (a peripheral muscarinic receptor antagonist), methyllycaconitine citrate (a selective α7 ni cotinic receptor antagonist), and tropicamide (a selective M4 muscarinic receptor antagonist). Collectively, our resul...
Source: Inflammation - Category: Allergy & Immunology Source Type: research

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Conclusion A great deal of progress is being made in the matter of treating aging: in advocacy, in funding, in the research and development. It can never be enough, and it can never be fast enough, given the enormous cost in suffering and lost lives. The longevity industry is really only just getting started in the grand scheme of things: it looks vast to those of us who followed the slow, halting progress in aging research that was the state of things a decade or two ago. But it is still tiny compared to the rest of the medical industry, and it remains the case that there is a great deal of work yet to be done at all...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Conclusion: The present study suggests that the extract of LMZ attenuates CFA-induced inflammatory pain by suppressing the ERK1/2 and NF-κB signaling pathway at both peripheral and central level. Introduction Pain is one of the most common symptoms in clinical practice, and inflammatory pain is the most important type of pain (Patapoutian et al., 2009). Inflammatory pain is a growing global health problem. In generally, there is a common course of progression in inflammation and pain share. When patients experience inflammation, they may develop hyperalgesia or allodynia to various mechanical, thermal, or che...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
In this study, we found that senescent chondrocytes isolated from OA patients secrete more EVs compared with nonsenescent chondrocytes. These EVs inhibit cartilage ECM deposition by healthy chondrocytes and can induce a senescent state in nearby cells. We profiled the miR and protein content of EVs isolated from the synovial fluid of OA joints from mice with SnCs. After treatment with a molecule to remove SnCs, termed a senolytic, the composition of EV-associated miR and protein was markedly altered. The senolytic reduced OA development and enhanced chondrogenesis, and these were attributable to several specific differenti...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
MicroRNA‑143‑3p contributes to the regulation of pain responses in collagen‑induced arthritis. Mol Med Rep. 2018 Jul 26;: Authors: Zhou LL, Zhu YM, Qian FY, Yuan CC, Yuan DP, Zhou XP Abstract Patients with rheumatoid arthritis (RA) suffer from pain, which is associated with inflammation, peripheral and central pain processing, and joint structure damage. The aim of the present study was to investigate a key microRNA (miR) and its target genes that are involved in the pain responses of RA, and to clarify the mechanism of pain regulation. Collagen‑induced arthritis (CIA) was induced in DBA/1 and ...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
CONCLUSIONS: Antibiotic prophylaxis for common soft tissue procedures of the hand is not associated with reduction in postoperative infection risk. While our analysis cannot account for factors that are not captured in the billing process, this study nevertheless provides strong evidence against unnecessary use of antibiotics before these procedures, especially given the difficulty of conducting a randomized prospective study with a sample size large enough to detect the effect of prophylaxis on the low baseline risk of infection. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID: 29432267 [PubMed - as supplied by publisher]
Source: Clinical Orthopaedics and Related Research - Category: Orthopaedics Authors: Tags: Clin Orthop Relat Res Source Type: research
Neuromodulation: Technology at the Neural Interface, EarlyView.
Source: Neuromodulation - Category: Neurology Source Type: research
In this study we investigated whether neuronal FcγRI contributes to antigen-specific pain in the naïve and rheumatoid arthritis model rats. In vitro calcium imaging and whole-cell patch clamp recordings in dissociated DRG neurons revealed that only the small-, but not medium- or large-sized DRG neurons responded to IgG-IC. Accordingly, in vivo electrophysiological recordings showed that intradermal injection of IgG-IC into the peripheral receptive field could sensitize only the C- (but not A-) type sensory neurons and evoke action potential discharges. Pain-related behavioral tests showed that intradermal inject...
Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research
In this study we investigated whether neuronal FcγRI contributes to antigen-specific pain in the naïve and rheumatoid arthritis model rats. In vitro calcium imaging and whole-cell patch clamp recordings in dissociated DRG neurons revealed that only the small-, but not medium- or large-sized DRG neurons responded to IgG-IC. Accordingly, in vivo electrophysiological recordings showed that intradermal injection of IgG-IC into the peripheral receptive field could sensitize only the C- (but not A-) type sensory neurons and evoke action potential discharges. Pain-related behavioral tests showed that intradermal inject...
Source: Brain, Behavior, and Immunity - Category: Neurology Authors: Tags: Brain Behav Immun Source Type: research
Conclusions. Preclinical Chloroquine toxicity can lead to early thinning in the central fovea as well as the parafoveal regions that is detected by SD-OCT. PMID: 26301102 [PubMed]
Source: Journal of Ophthalmology - Category: Opthalmology Tags: J Ophthalmol Source Type: research
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