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HSP70 inhibitors upregulate prostaglandin E1-induced synthesis of interleukin-6 in osteoblasts.

Interleukin-6 (IL-6) is a pro-inflammatory and bone-resorptive cytokine that also regulates bone formation. We previously showed that prostaglandin E1 (PGE1) induces the synthesis of IL-6 by activating p44/p42 mitogen-activated protein kinase (MAPK), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and p38 MAPK in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether heat shock protein 70 (HSP70), a molecular chaperone that coordinates protein folding and homeostasis, affects PGE1-stimulated IL-6 synthesis in MC3T3-E1 cells through the MAPK activation. The osteoblast-like MC3T3-E1 cells were treated with HSP70 inhibitors-VER-155008 and YM-08-, PD98059, SB203580 or SP600125 and then stimulated with PGE1. IL-6 synthesis was evaluated using an IL-6 enzyme-linked immunosorbent assay kit. IL-6 mRNA expression was measured by real-time RT-PCR. The phosphorylation of p38 MAPK was evaluated by Western blotting. We found that VER-155008, an HSP70 inhibitor, enhanced the PGE1-stimulated IL-6 release and IL-6 mRNA expression. YM-08, another HSP70 inhibitor, also enhanced PGE1-stimulated IL-6 release. PD98059, a p44/p42 MAPK inhibitor, and SP600125, a SAPK/JNK inhibitor, upregulated PGE1-stimulated IL-6 release. On the other hand, SB203580, a p38 MAPK inhibitor, suppressed PGE1-stimulated IL-6 release. YM-08 stimulated the PGE1-induced phosphorylation of p38 MAPK. SB203580 suppressed the amplification by YM-08 of the PGE1-stimulated IL-6 release. Our results suggest that HSP70 inhibitors upregulate the PGE1-stimulated IL-6 synthesis through p38 MAPK in osteoblasts and therefore affect bone remodeling.

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A cross-sectional assessment of knowledge, awareness of risk factors, and perceptions of thyroid disease (TD) among adults living in Saudi Arabia – A community based study.

The incidence of thyroid diseases has tripled in the last three decades, and the prevalence is rising rapidly irrespective of gender and genetics. This study aimed to assess the Knowledge, awareness of risk factors, and perceptions of thyroid disease among the Saudi Community in Saudi Arabia.

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Molecular Mechanism of the – Herb Pair in Migraine Therapy Based on Network Pharmacology and Molecular Docking.

This work studied the molecular mechanism of the – herb pair (SAHP) in migraine treatment.

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Face mask and protective eyewear-associated headache among healthcare workers during the COVID-19 pandemic.

The objective of this study was to investigate the prevalence, clinical features, and factors related to personal protective-associated headaches.

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Retracted: Perioperative Nursing Care of Vascular Decompression for Trigeminal Neuralgia under AR Medical Technology.

[This retracts the article DOI: 10.1155/2021/9921094.].

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Distribution profiles of diphenhydramine and lidocaine in scalp, axillary, and pubic hairs measured by micro-segmental hair analysis: good indicator for discrimination between administration and external contamination of the drugs.

Drug distribution in scalp hair can provide historical information about drug use, such as the date and frequency of drug ingestion. We previously developed micro-segmental hair analysis, which visualizes drug distribution at 0.4-mm intervals in individual hairs. The present study examines whether the distribution profiles of drugs can be markers for the administration or external contamination of the drugs using scalp, axillary, and pubic hairs.

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[Points of undenatured type II collagen application in musculoskeletal pain syndromes treatment].

The dominant collagen of the cartilaginous matrix in adults is type II collagen. The amount of type II collagen in the intercellular matrix of cartilage is significantly reduced against the background of musculoskeletal system diseases. The basis of articular cartilage is hyaline cartilage tissue consisting of chondrocytes with tissue-specific antigens that induce the production of antibodies in patients with osteoarthritis (OA). Today, new approaches are being considered in the treatment of OA with the use of udenatured type II collagen (UC-II). Such molecular mechanisms of action of UC-II as the formation of a systemic response through oral tolerance are discussed, since the induction of tolerance is the immune pathway, by default, in the intestine. A number of experimental, preclinical (on volunteers) and clinical studies have shown the effectiveness and safety of the use of UC-II in OA. Standardized extracts of UC-II exhibit anti-inflammatory, immunoregulatory, chondroprotective effects, contributing to the reduction of pain symptoms of OA. Against the background of taking UC-II with induced OA, there is a statistically significant decrease in the level of proinflammatory cytokines, such as interleukin (IL-1β, IL-6), tumor necrosis factor alpha (TNF), C-reactive protein (CRP) in serum and the level of max proteinases (MMP-3), nucleated factor «kappa-bi» (NF-κB) in the knee joint. UC-II significantly inhibits the production of prostaglandin E2 (by 20%) and the expression of genes encoding proinflammatory proteins. In experimental models and in OA patients, a decrease in the severity of pain syndrome, an increase in endurance, mobility and an improvement in the functional state of the joints were noted. Clinically, no changes in the structure of the muscle fiber were detected with increased physical exertion. With OA on the background of UC-II (10-40 mg/s), there was a statistically significant decrease in joint pain according to WOMAC. A promising direction of OA therapy is the combination of UC-II with chondroitin sulfate and glucosamine sulfate.

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Clusters of conditions among US service members diagnosed with mild TBI from 2017 through 2019.

Many US Military Service Members (SMs) newly diagnosed with mild Traumatic Brain Injury (mTBI) may exhibit a range of symptoms and comorbidities, making for a complex patient profile that challenges clinicians and healthcare administrators. This study used clustering techniques to determine if conditions co-occurred as clusters among those newly injured with mTBI and up to one year post-injury.

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Missed diagnosis of septic arthritis due to invasive pneumococcal disease.

A 61-year-old woman with severe gout, chronic kidney disease, type II diabetes, and heart failure with reduced ejection fraction was admitted with acute onset bilateral hand swelling and pain following a trauma. She was managed for a severe gout flare, but her symptoms, leukocytosis, and inflammatory markers did not improve. Six days into the hospital course, she developed fevers. Blood cultures grew Intravenous antibiotics were started, and the patient underwent multiple incision and debridements of the bilateral hands with improvement in symptoms and clinical status. Septic arthritis secondary to is uncommon. We highlight this case to recognize that septic arthritis should always be considered when a patient presents with a painful, erythematous joint. Pneumococcal vaccination reduces the incidence of invasive pneumococcal disease, and should be prioritized for those at high risk for invasive disease and who are immunocompromised.

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Infected abdominal aortic aneurysm due to Salmonella in a patient with diabetes mellitus.

We present a case of an elderly patient with uncontrolled diabetes mellitus, who presented with recurrent fever and abdominal pain, after which he was diagnosed with an infected abdominal aortic aneurysm, which represents only 1% of all aneurysms. The patient underwent surgical resection of the aneurysm, rifampicine-impregnated Dacron graft placement and intravenous antibiotic treatment. Microbiology reported Salmonella infection in the aneurysm. Currently, the patient is asymptomatic and without laboratory evidence of inflammatory process.

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