The enhanced differentiation and activation of osteoclasts (OCs) in the inflammatory arthritis such as rheumatoid arthritis (RA) and gout causes not only local bone erosion, but also systemic osteoporosis, leading to functional disabilities and morbidity. The induction and amplification of NFATc1, a master regulator of OC differentiation, is mainly regulated by receptor activator of NF-κB (RANK) ligand-RANK and calcium signaling which are amplified in the inflammatory milieu, as well as by inflammatory cytokines such as TNFα, IL-1β and IL-6. Moreover, the predominance of CD4+ T cell subsets, which varies depending on the condition of inflammatory diseases, can determine the fate of OC differentiation. Anti-citrullinated peptide antibodies which are critical in the pathogenesis of RA can bind to the citrullinated vimentin on the surface of OC precursors, and in turn promote OC differentiation and function via IL-8. In addition to adaptive immunity, the activation of innate immune system including the nucleotide oligomerization domain leucine rich repeat with a pyrin domain 3 inflammasome and TLRs can regulate OC maturation. The emerging perspectives about the diverse and close interactions between the immune cells and OCs in inflammatory milieu can have a significant impact on the future direction of drug development.
Adaptive Immunity ; Antibodies ; Arthritis ; Arthritis, Rheumatoid ; Calcium Signaling ; Cytokines ; Gout ; Immune System ; Inflammasomes ; Interleukin-6 ; Interleukin-8 ; Leucine ; Osteoclasts ; Osteolysis ; Osteoporosis ; T-Lymphocyte Subsets ; Vimentin

BACKGROUND: The aim of this study was to clarify the topographical relationships between the dorsal scapular nerve (DSN) and the dorsal scapular artery (DSA) in the interscapular region to identify safe and convenient injection points related to DSN blockade. METHODS: Thirty shoulders of embalmed Korean cadavers and 50 live subjects were used for dissection and ultrasound (US) analysis. RESULTS: The running patterns of the DSA and DSN in the interscapular region were classified into 3 types. Type I was defined as nerves that were medial to the artery and parallel without changing location (80.0% of specimens). In type II (13.3%), the nerve and artery traversed one another only one time over their entire length. In type III (6.7%), the nerve and artery traversed one another, resembling a twist. Above the level of the scapular spine, the nerve was always medial to the artery. Below the scapular spine, the number of arteries was obviously decreased. Most of the arteries were lateral to the medial border of the scapula, except at the level of the superior angle of the scapula artery (SA). The positional tendency of the DSN toward the medial or lateral sides from the medial border of the scapula was similar. In US imaging of live subjects, the DSA was most observed at the level of the SA (94.0%). CONCLUSIONS: Results of this study enhance the current knowledge regarding the pathway of the DSN and DSA and provide helpful information for selective diagnostic nerve blocks in the interscapular region.
Arteries ; Cadaver ; Diagnosis ; Nerve Block ; Running ; Scapula ; Shoulder ; Spine ; Ultrasonography

Psychiatric disorders are a prevalent global health problem, over 900 million individuals affected by a continuum of mental and substance use disorders. Due to this high prevalence, and the substantial direct and indirect societal costs, it is essential to understand the underlying mechanisms of these disorders to facilitate development of new and more effective treatments. Since the advent of recombinant DNA technologies in the early 1980s, genetically modified rodent models have significantly contributed to the genetic and molecular basis of psychiatric disorders. Despite significant advancements, many challenges remain after unsuccessful drug development based on rodent models. Recent human genetics show the polygenetic nature of mental disorders, identifying hundreds of allelic variants that confer increased risk. However, given the complexity of the brain, with many unique cell types, gene expression profiles, and developmental trajectories, proper animal models are needed more than ever to dissect genes and circuits in a cell type-specific manner to advance our understanding and treatment of psychiatric disorders. In this mini-review, we highlight current challenges and promises of using rodent models in advancing science and drug development, focusing on advanced techniques, and their applications to rodent models of psychiatric disorders.

Electroconvulsive shock (ECS) induces not only an antidepressant effect but also adverse effects such as amnesia. One potential mechanism underlying both the antidepressant and amnesia effect of ECS may involve the regulation of serotonin (5-hydroxytryptamine) 6 (5-HT6) receptor, but less is known about the effects of acute ECS on the changes in 5-HT6 receptor expression in the hippocampus. In addition, as regulation of 5-HT receptor expression is influenced by the number of ECS treatment and by interval between ECS treatment and sacrifice, it is probable that magnitude and time-dependent changes in 5-HT6 receptor expression could be influenced by repeated ECS exposure. To explore this possibility, we observed and compared the changes of 5-HT6 receptor immunoreactivity (5-HT6 IR) in rat hippocampus at 1, 8, 24, or 72 h after the treatment with either a single ECS (acute ECS) or daily ECS for 10 days (chronic ECS). We found that acute ECS increased 5-HT6 IR in the CA1, CA3, and granule cell layer of hippocampus, reaching peak levels at 8 h and returning to basal levels 72 h later. The magnitude and time-dependent changes in 5-HT6 IR observed after acute ECS were not affected by chronic ECS. These results demonstrate that both acute and chronic ECS transiently increase the 5-HT6 IR in rat hippocampus, and suggest that the magnitude and time-dependent changes in 5-HT6 IR in the hippocampus appear not to be influenced by repeated ECS treatment.
Amnesia ; Animals ; Electroshock* ; Hippocampus* ; Rats* ; Serotonin

Although growth associated protein-43 (GAP-43) is known to play a significant role in the regulation of axonal growth and the formation of new neuronal connections in the hippocampus, there is only a few studies on the effects of acute stress on GAP-43 mRNA expression in the hippocampus. Moreover, the effects of repeated citalopram treatment on chronic mild stress (CMS)-induced changes in GAP-43 mRNA expression in the hippocampus have not been explored before. To explore this question, male rats were exposed to acute immobilization stress or CMS. Also, citalopram was given prior to stress everyday during CMS procedures. Acute immobilization stress significantly increased GAP-43 mRNA expression in all subfields of the hippocampus, while CMS significantly decreased GAP-43 mRNA expression in the dentate granule cell layer (GCL). Repeated citalopram treatment decreased GAP-43 mRNA expression in the GCL compared with unstressed controls, but this decrease was not further potentiated by CMS exposure. Similar decreases in GAP-43 mRNA expression were observed in CA1, CA3 and CA4 areas of the hippocampus only after repeated citalopram treatment in CMS-exposed rats. This result indicates that GAP-43 mRNA expression in the hippocampus may differently respond to acute and chronic stress, and that repeated citalopram treatment does not change CMS-induced decreases in GAP-43 mRNA expression in the GCL.
Animals ; Axons ; Citalopram ; GAP-43 Protein ; Hippocampus ; Humans ; Immobilization ; Male ; Neurons ; Rats ; RNA, Messenger

Animals ; Cats ; Diagnostic Tests, Routine ; Hemorrhage ; Humans ; Injury Severity Score ; Mortality ; Odds Ratio ; Resuscitation ; ROC Curve ; Sensitivity and Specificity

Hodgson's bats are critically endangered in South Korea. This study analyzed the concentrations of elements in liver, kidney, and intestine tissues from a Hodgson's bat found dead in the wild. The concentrations of essential elements followed the order Fe > Zn > Cu >Mn > Se in the three tissues. Hg was detected at the highest concentrations among the non-essential elements analyzed in the liver and kidney tissues, while As was the most highly concentrated non-essential element in the intestine. To the best of our knowledge, this is the first study of tissue element concentrations in Hodgson's bats.
Chiroptera ; Intestines* ; Kidney* ; Korea ; Liver*