Articles: cations.
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In our prospective cross-sectional study, we comprehensively characterized Parkinson disease (PD)-related pain in monocentrically recruited patients with PD using standardized tools of pain assessment and categorization. One hundred fifty patients were systematically interviewed and filled in questionnaires for pain, depression, motor, and nonmotor symptoms. Patients with PD-related pain (PD pain), patients without PD-related pain (no PD pain), and patients without pain (no pain) were compared. ⋯ Parkinson disease-related pain was most frequently located in the feet (51/90, 57%), mainly at the toe joints (22/51, 43%). 38/90 (42%) patients with PD-related pain received analgesic medication with nonsteroidal anti-inflammatory drugs being the most frequently used (31/42, 82%) and opioids most effective (70% pain reduction of individual maximum pain intensities, range 22%-100%, confidence interval 50%-90%). All patients received oral PD treatment; however, levodopa equivalent dose showed no correlation with mean pain intensities (Spearman ρ = 0.027, P > 0.05). Our data provide a comprehensive analysis of PD-related pain, giving evidence for mainly non-neuropathic podalgia, which bears the potential to rethink assessment and analgesic treatment of pain in PD in clinical practice.
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Proinflammatory hyperactivation of Kupffer cells (KCs) is foremost involved in the pathogenesis of sepsis-induced liver injury. Our previous study found that stimulator of interferon genes (STING) signaling was activated in KCs in response of lipopolysaccharide (LPS) and knocking down dynamin-related protein 1 (DRP1) in KCs effectively inhibited the activation of STING signaling and the subsequent production of proinflammatory cytokines. In this study, we demonstrated that in vivo treatment with mitochondrial division inhibitor 1 (Mdivi-1), a selective inhibitor of DRP1, alleviated cecal ligation and puncture (CLP)-induced liver injury with the improvement of liver pathology and function. ⋯ The further study showed that Mdivi-1 markedly attenuated STING signaling activation in KCs and inhibited systemic inflammatory response. Importantly, DMXAA application in CLP mice blunted Mdivi-1's liver protection effect. Taken together, our study confirmed Mdivi-1 effectively alleviated CLP-induced liver injury partially through inhibiting STING signaling activation in KCs, which provides new insights and a novel potential pharmacological therapeutic target for treating septic liver injury.
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Introduction: Intestinal flora and the translocation of its products, such as muramyl dipeptide (MDP), are common causes of sepsis. MDP is a common activator of the intracellular pattern recognition receptor NOD2, and MDP translocation can cause inflammatory damage to the small intestine and systemic inflammatory responses in rats. Therefore, this study investigated the effects of MDP on the intestinal mucosa and distant organs during sepsis and the role of the NOD2/AMPK/LC3 pathway in MDP-induced mitochondrial dysfunction in the intestinal epithelium. ⋯ Compared to the MDP+LPS groups, the MDP+SPEN+LPS groups had decreased IL-6 and MDP production, increased AMPK and LC3 protein expression, and protected mitochondrial and organ functions. Conclusions: MDP translocation reduced mitochondrial autophagy by regulating the NOD2/AMPK/LC3 pathway, causing mitochondrial dysfunction. SPEN protected against MDP-induced impairment of intestinal epithelial mitochondrial function during sepsis.
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Few analgesics identified using preclinical models have successfully translated to clinical use. These translational limitations may be due to the unidimensional nature of behavioral response measures used to assess rodent nociception. Advances in high-speed videography for pain behavior allow for objective quantification of nuanced aspects of evoked paw withdrawal responses. ⋯ Similar high-speed videography assessments were performed in CFA- and vehicle-treated animals, and the cumulative data failed to reveal an effect of CFA injection on withdrawal as measured by high-speed videography. This study does not support using paw height, velocity, or pain score measurements from high-speed recordings to delineate behavioral responses to innocuous and noxious stimuli. Our group encourages the continued use of traditional mechanical withdrawal assessments until additional high-speed withdrawal measures are validated in established pain models.