Background: Chronic pain significantly affects daily activities, mental health, and the interpersonal relationships of patients. Consequently, physicians use various treatments to manage pain. This study investigated the perceptions of treatment, accompanying symptoms, and other problems in patients with chronic pain. Methods: The authors enrolled patients with chronic pain from 19 university hospitals in South Korea. Data was collected on age, gender, diagnosis, disease duration, severity of pain, perception of pain treatment, and accompanying symptoms or problems using an anonymous survey comprising 19 questions. Results: In total, 833 patients with chronic pain completed the survey, and 257 (31.0%) and 537 (64.5%) patientsexpressed concerns about the potential adverse effects of medication and opioid addiction, respectively. Personalitychanges such as irritability or anger were the most frequent accompanying symptoms in 507 (63.8%) patients, followed by depression and sleep disturbance in 462 (58.1%) and 450 (54.5%) patients, respectively. Depression (P = 0.001) and anxiety (P = 0.029) were more common among women, whereas divorce (P = 0.016), family conflict (P < 0.001), unemployment (P < 0.001), suicide attempts (P < 0.001), and restrictions on economic activity (P < 0.001) were more common among men. The frequency of accompanying symptoms, except for suicidal ideation,was higher in the younger patients aged ≤ 40 years than in the older patients aged > 40 years. Conclusions Many patients with chronic pain had concerns about adverse effects or medication tolerance and experienced anxiety, depression, or sleep disturbances. The prevalence of accompanying problems varies according to age and gender.

PKD1 regulates a number of cellular processes through the formation of complexes with the PKD2 ion channel or transient receptor potential classical (TRPC) 4 in the endothelial cells. Although Ca 2+ modulation by polycystins has been reported between PKD1 and TRPC4 channel or TRPC1 and PKD2, the function with TRPC subfamily regulated by PKD2 has remained elusive. We confirmed TRPC4 or TRPC5 channel activation via PKD1 by modulating G-protein signaling without change in TRPC4/C5 translocation. The activation of TRPC4/C5 channels by intracellular 0.2 mM GTPγS was not significantly different regardless of the presence or absence of PKD1. Furthermore, the C-terminal fragment (CTF) of PKD1 did not affect TRPC4/C5 activity, likely due to the loss of the N-terminus that contains the G-protein coupled receptor proteolytic site (GPS). We also investigated whether TRPC1/C4/C5 can form a heterodimeric channel with PKD2, despite PKD2 being primarily retained in the endoplasmic reticulum (ER). Our findings show that PKD2 is targeted to the plasma membrane, particularly by TRPC5, but not by TRPC1. However, PKD2 did not coimmunoprecipitate with TRPC5 as well as with TRPC1. PKD2 decreased both basal and La 3+ -induced TRPC5 currents but increased M 3 R-mediated TRPC5 currents. Interestingly, PKD2 increased STAT3 phosphorylation with TRPC5 and decreased STAT1 phosphorylation with TRPC1. To be specific, PKD2 and TRPC1 compete to bind with TRPC5 to modulate intracellular Ca 2+ signaling and reach the plasma membrane. This interaction suggests a new therapeutic target in TRPC5 channels for improving vascular endothelial function in polycystic kidney disease.

Fine particulate matter (FPM) is a major component of air pollution and has emerged as a significant global health concern owing to its adverse health effects. Previous studies have investigated the correlation between bone health and FPM through cohort or review studies. However, the effects of FPM exposure on bone health are poorly understood. This study aimed to investigate the effects of FPM on bone health and elucidate these effects in vitro and in vivo using mice. Micro-CT analysis in vivo revealed FPM exposure decreased bone mineral density, trabecular bone volume/total volume ratio, and trabecular number in the femurs of mice, while increasing trabecular separation. Histological analysis showed that the FPM-treated group had a reduced trabecular area and an increased number of osteoclasts in the bone tissue. Moreover, in vitro studies revealed that low concentrations of FPM significantly enhanced osteoclast differentiation. These findings further support the notion that short-term FPM exposure negatively impacts bone health, providing a foundation for further research on this topic.

Schwann cells are the most abundant cells in the peripheral nervous system, maintaining the development, function and regeneration of peripheral nerves. Defects in these Schwann cells injury response potentially contribute to the pathogenesis of diabetic peripheral neuropathy (DPN), a common complication of diabetes mellitus. The protein p66shc is essential in regulating oxidative stress responses, autophagy induction and cell survival, and is also vital in the development of DPN. In this study, we hypothesized that p66shc mediates high glucose-induced oxidative stress and autophagic dysfunction. In Schwann cells treated with high glucose; p66shc expression, levels of reactive oxygen species, autophagy impairment, and early apoptosis were elevated. Inhibition of p66shc gene expression by siRNA reversed high glucose-induced oxidative stress, autophagy impairment, and early apoptosis. We also demonstrated that the levels of p66shc was increased, while autophagy-related proteins p62 and LC3 (LC3-II/I) were suppressed in the sciatic nerve of streptozotocin-induced diabetes mice. P66shc-deficient mice exhibited the improvement in autophagy impairment after diabetes onset. Our findings suggest that the p66 plays a crucial role in Schwann cell dysfunction, identifying its potential as a therapeutic target.

Microglial activation during aging is associated with neuroinflammation and cognitive impairment. Galectin-3 plays a crucial role in microglial activation and phagocytosis. However, the role of galectin-3 in the aged brain is not completely understood. In the present study, we investigated aging-related mechanisms and microglial galectin-3 expression in the mouse hippocampus using female 6-, 12-, and 24-month-old C57BL/6 mice. Western blot analysis revealed neurodegeneration, blood-brain barrier leakage, and increased levels of neuroinflammation-related proteins in 24-month-old mice compared to 6- and 12-month-old mice. Immunohistochemistry revealed an increase in activated microglia in the hippocampus of 24-month-old mice compared to 6- and 12-month-old mice. Furthermore, we found more galectin-3 and triggering receptor expressed on myeloid cells-2-positive microglia in 24-month-old mice compared to 6- and 12-month-old mice. Using primary mouse microglial cells, galectin -3 was also increased by lipopolysaccharide treatment. These findings suggest that galectin-3 may play an important role in microglial activation and neuroinflammation during brain aging.

Heart diseases are a significant contributor to global morbidity and mortality, and despite their diverse and complex mechanisms, treatment options remain limited. Maltol, a natural compound with antioxidant and anti-inflammatory activities, exhibits potential for addressing this need. This study evaluates the cardioprotective effects of maltol in isoproterenol (ISO)-induced cardiac stress models and Duchenne muscular dystrophy (DMD). Maltol’s cardiac cytotoxicity was assessed in rodent (H9c2) and human (AC16) cells and compared with that of dapagliflozin to illustrate its cardiac safety. In ISO-induced stress models, maltol significantly reduced hypertrophic markers and inflammation while enhancing autophagy and antioxidant pathways. In the mdx mice, a DMD model, maltol treatment improved cardiac contractility and reduced pathogenic remodeling. Enhanced phosphorylation of phospholamban and trends toward higher SERCA2a expression indicated enhanced Ca 2+ handling, which is crucial in DMD cardiomyopathy. This study demonstrated that maltol has the potential to provide therapeutic benefits for DMD and other cardiac conditions characterized by hypertrophy and inflammation, as evidenced by its well-known antioxidant properties, low cytotoxicity, and capacity to enhance cardiac function and Ca 2+ handling.

Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE -/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE –/–mice. This study highlights PA9RA's potential as a promising therapeutic agent for atherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.

Purpose: Persistent postoperative stiffness is a common complication after arthroscopic rotator cuff repair (ARCR).We hypothesized that a subacromial steroid injection (SAI) may improve the early outcomes in patients with persistent stiffness without increasing steroid-associated complications. Therefore, we evaluated the effectiveness and safety of SAI in patients with persistent stiffness 3 months after ARCR. Methods: We retrospectively analyzed 300 ARCR cases performed between January 2012 and May 2014, in which repair integrity was confirmed at postoperative 3 months. Patients were divided into SAI and control groups. The SAI group received a single SAI (triamcinolone 40 mg and ropivacaine 52.5 mg) to address postoperative stiffness, with no additional SAI thereafter. The control group did not receive any injections until the final follow-up. Functional and radiological outcomes were compared between the two groups. Results: The mean follow-up period was 18.1±4.7 months (range, 12.1–37.2 months), with no difference between groups (p=0.731). At the time of injection, the range of motion was significantly lower in the SAI (all p＜0.001). However, functional outcomes were comparable between the two groups at 3 months after injection and the final follow-up (all p＞ 0.05). The healing failure rate at the final follow-up also did not differ between the SAI and control groups (14.9% vs. 13.2%, p=0.671). Conclusion This short-term follow-up study suggests that the administration of a single SAI to treat persistent stiffness at 3 months after ARCR may improve functional recovery without increasing the risk of healing failure.