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Rheumatoid arthritis (RA) is an inflammatory disease marked by a massive proliferation of synovial cells in the joints. In this study, we investigated the pro-apoptotic effects of docosahexaenoic acid (DHA) in human fibroblast-like synovial cells from RA patients (RA-FLS). An in vitro study using MH7A cells showed that DHA treatment induced caspase-8-dependent apoptosis in a dose-dependent manner and reduced the TNF-α-mediated induction of MMP-9 and IL-1β. DHA also induced the phosphorylation of eIF2α, the expression of the ER stress markers ATF4 and C/EBP homologous protein (CHOP), and death receptor 5 (DR5). The knockdown of CHOP or DR5 increased cell viability and reduced apoptosis in DHA-treated cells. Furthermore, the knockdown of CHOP reduced DHA-mediated DR5 expression, while the overexpression of CHOP increased DR5 expression. We also found that DHA treatment induced the accumulation of reactive oxygen species (ROS), and pretreatment with the anti-oxidant Tiron effectively abrogated not only the expression of CHOP and DR5, but also DHA-induced apoptosis. Under this condition, cell viability was increased, while PARP-1 cleavage and caspase-8 activation were reduced. All the findings were reproduced in human primary synovial cells obtained from RA patients. These results suggest that the DHA-mediated induction of ROS and CHOP induced apoptosis through the upregulation of DR5 in RA-FLSs, and that CHOP could be used as a therapy for RA.

Radioiodine (RI) therapy is known to cause salivary gland (SG) dysfunction. The effects of antioxidants on RI-induced SG damage have not been well described. This study was performed to investigate the radioprotective effects of alpha lipoic acid (ALA) administered prior to RI therapy in a mouse model of RI-induced sialadenitis. Four-week-old female C57BL/6 mice were divided into four groups (n = 10 per group): group I, normal control, group II, ALA alone (100 mg/kg), group III, RI alone (0.01 mCi/g body weight, orally), and group IV, ALA + RI (ALA at 100 mg/kg, 24 h and 30 min before RI exposure at 0.01 mCi/g body weight). The animals in these groups were divided into two subgroups and euthanized at 30 or 90 days post-RI treatment. Changes in salivary 99mTc pertechnetate uptake and excretion were tracked by single-photon emission computed tomography. Salivary histological examinations and TUNEL assays were performed. The 99mTc pertechnetate excretion level recovered in the ALA treatment group. Salivary epithelial (aquaporin 5) cells of the ALA + RI group were protected from RI damage. The ALA + RI group exhibited more mucin-containing parenchyma and less fibrotic tissues than the RI only group. Fewer apoptotic cells were observed in the ALA + RI group compared to the RI only group. Pretreatment with ALA before RI therapy is potentially beneficial in protecting against RI-induced salivary dysfunction.

Background: Endothelial progenitor cells (EPCs) have the potential to protect against atherothrombotic event occurrences. There are no data to evaluate the impact of cilostazol on EPC levels in high-risk patients. Methods: We conducted a randomized, double-blind, placebo-controlled trial to assess the effect of adjunctive cilostazol on EPC mobilization and platelet reactivity in patients with acute myocardial infarction (AMI). Before discharge, patients undergoing percutaneous coronary intervention (PCI) were randomly assigned to receive cilostazol SR capsule (200-mg) a day (n = 30) or placebo (n = 30) on top of dual antiplatelet therapy (DAPT) with clopidogrel and aspirin. Before randomization (baseline) and at 30-day follow-up, circulating EPC levels were analyzed using flow cytometry and hemostatic measurements were evaluated by VerifyNow and thromboelastography assays. The primary endpoint was the relative change in EPC levels between baseline and 30-day. Results: At baseline, there were similar levels of EPC counts between treatments, whereas patients with cilostazol showed higher levels of EPC counts compared with placebo after 30 days. Cilostazol versus placebo treatment displayed significantly higher changes in EPC levels between baseline and follow-up (&Delta, CD133+/KDR+: difference 216%, 95% confidence interval (CI) 44~388%, p = 0.015, &Delta, CD34+/KDR+: difference 183%, 95% CI 25~342%, p = 0.024). At 30-day follow-up, platelet reactivity was lower in the cilostazol group compared with the placebo group (130 &plusmn, 45 versus 169 &plusmn, 62 P2Y12 Reaction Unit, p = 0.009). However, there were no significant correlations between the changes of EPC levels and platelet reactivity. Conclusion: Adjunctive cilostazol on top of clopidogrel and aspirin versus DAPT alone is associated with increased EPC mobilization and decreased platelet reactivity in AMI patients, suggesting its pleiotropic effects against atherothrombotic events (NCT04407312).

Dance therapy can improve motor skills, balance, posture, and gait in people diagnosed with Parkinson’s disease (PD) and healthy older adults (OA). It is not clear how specific movement patterns during dance promote these benefits. The purpose of this cohort study was to identify differences and complexity in dance movement patterns among different dance styles for PD and OA participants in community dance programs using approximate entropy (ApEn) analysis. The hypothesis was that PD participants will show greater ApEn during dance than OA participants and that the unique dance style of tango with more pronounced foot technique and sharp direction changes will show greater ApEn than smoother dance types such as foxtrot and waltz characterized by gradual changes in direction and gliding movement with rise and fall. Individuals participated in one-hour community dance classes. Movement data were captured using porTable 3D motion capture sensors attached to the arms, torso and legs. Classes were also video recorded to assist in analyzing the dance steps. Movement patterns were captured and ApEn was calculated to quantify the complexity of movements. Participants with PD had greater ApEn in right knee flexion during dance movements than left knee flexion (p = 0.02), greater ApEn of right than left hip flexion (p = 0.05), and greater left hip rotation than right (p = 0.03). There was no significant difference in ApEn of body movements (p > 0.4) or mean body movements (p > 0.3) at any body-segment in OA. ApEn analysis is valuable for quantifying the degree of control and predictability of dance movements and could be used as another tool to assess the movement control of dancers and aid in the development of dance therapies.

Avian pathogenic Escherichia coli (APEC) causes colibacillosis, which is an economically important disease in the poultry industry worldwide. The present study investigated O-serogroups, phylogenetic groups, antimicrobial resistance, and the existence of virulence-associated genes (VAGs) and antimicrobial resistance genes in 125 APEC isolates between 2018 and 2019 in Korea. The phylogenetic group B2 isolates were confirmed for human-related sequence types (STs) through multi-locus sequence typing (MLST). O-serogroups O2 (12.5%) and O78 (10.3%) and phylogenetic group B1 (36.5%) and A (34.5%) were predominant in chicken and duck isolates, respectively. Out of 14 VAGs, iucD, iroN, hlyF, and iss were found significantly more in chicken isolates than duck isolates (p &lt, 0.05). The resistance to ampicillin, ceftiofur, ceftriaxone, and gentamicin was higher in chicken isolates than duck isolates (p &lt, 0.05). The multidrug resistance (MDR) rates of chicken and duck isolates were 77.1% and 65.5%, respectively. One isolate resistant to colistin (MIC 16 μg/mL) carried mcr-1. The B2-ST95 APEC isolates possessed more than 9 VAGs, and most of them were MDR (82.4%). This report is the first to compare the characteristics of APEC isolates from chickens and ducks in Korea and to demonstrate that B2-ST95 isolates circulating in Korea have zoonotic potential and pose a public health risk.

Chikungunya virus (CHIKV) infection can result in chronic and debilitating arthralgia affecting humans in tropical and subtropical regions around the world, yet there are no licensed vaccines to prevent infection. DNA launched virus like particle (VLP) vaccines represent a potentially safer alternative to traditional live-attenuated vaccines, however, fully characterized immunocompetent mouse models which appropriately include both male and female animals for preclinical evaluation of these, and other, vaccine platforms are lacking. Utilizing virus stocks engineered to express mutations reported to enhance CHIKV virulence in mice, infection of male and female immunocompetent mice was evaluated, and the resulting model utilized to assess the efficacy of candidate DNA launched CHIKV VLP vaccines. Results demonstrate the potential utility of DNA launched VLP vaccines in comparison to a live attenuated CHIKV vaccine and identify gender differences in viral RNA loads that impact interpretation of vaccine efficacy and may have important implications for future CHIKV vaccine development.

The immunologic aspects of radiation pneumonitis (RP) are unclear. We analyzed variations in cytokine profiles between patients with grade (Gr) 0–1 and Gr ≥ 2 RP. Fifteen patients undergoing concurrent chemoradiotherapy for non-small cell lung cancer were included. Blood samples of 9 patients with Gr 0–1 and 6 with Gr ≥ 2 RP were obtained from the Biobank. Cytokine levels were evaluated using an enzyme linked immunosorbent assay at before radiotherapy (RT) initiation, 1, 3, and 6 weeks post-RT initiation, and 1 month post-RT completion. Concentrations of granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-6, IL-10, IL-13, IL-17, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β were analyzed, none were related to the occurrence of Gr ≥ 2 RP at pre-RT initiation. At 3 weeks, relative changes in the G-CSF, IL-6, and IFN-γ levels differed significantly between the groups (p = 0.026, 0.05 and 0.026, respectively). One month post-RT completion, relative changes of IL-17 showed significant differences (p = 0.045), however, relative changes in TNF-α, IL-10, IL-13, and TGF-β, did not differ significantly. Evaluation of changes in IL-6, G-CSF, and IFN-γ at 3 weeks after RT initiation can identify patients pre-disposed to severe RP. The mechanism of variation in cytokine levels in relation to RP severity warrants further investigation.

Light is a major environmental factor affecting the regulation of secondary metabolites, such as pigments and flavor. The Solanaceae plant family has diverse patterns of fruit metabolisms that serve as suitable models to understand the molecular basis of its regulation across species. To investigate light-dependent regulation for fruit pigmentation and volatile flavors, major fruit pigments, their biosynthetic gene expression, and volatiles were analyzed in covered fruits of tomato and bell pepper. Immature covered fruits were found to be ivory in color and no chlorophyll was detected in both plants. The total carotenoid content was found to be reduced in ripe tomato and bell pepper under cover. Naringenin chalcone decreased more than 7-fold in ripe tomato and total flavonoids decreased about 10-fold in immature and ripe pepper fruit under light deficiency. Light positively impacts fruit pigmentation in tomato and bell pepper by regulating gene expression in carotenoid and flavonoid biosynthesis, especially phytoene synthase and chalcone synthase, respectively. Nineteen volatile flavors were detected, and seven of these exhibited light-dependent regulations for both ripe tomato and pepper. This study will help in improving fruit quality and aid future research works to understand the molecular mechanisms regulating the influence of light-dependency on pigments and flavor volatiles.

The objective was to investigate if high cadence cycling altered non-motor cognition and depression symptoms in individuals with Parkinson&rsquo, s disease (PD) and whether exercise responses were influenced by brain-derived neurotrophic factor (BDNF) Val66Met polymorphism. Individuals with idiopathic PD who were &ge, 50 years old and free of surgical procedures for PD were recruited. Participants were assigned to either a cycling (n = 20) or control (n = 15) group. The cycling group completed three sessions of high cadence cycling on a custom motorized stationary ergometer. The primary outcome was cognition (attention, executive function, and emotion recognition were assessed via WebNeuro&reg, and global cognition via Montreal Cognitive Assessment). Depression symptoms were assessed via Beck Depression Inventory-II. There was a main effect of time for emotional recognition (p = 0.048), but there were no other changes in cognition or depression symptoms. Regardless of intervention or Val66Met polymorphism, high cadence cycling does not alter cognition or depression symptoms after three sessions in one week.