Cannabiorcol as a novel inhibitor of the p38/MSK-1/NF-κB signaling pathway, reducing matrix metalloproteinases in osteoarthritis.

BACKGROUND: The bioactivity and potential medicinal applications of cannabiorcol, a lesser-known derivative of Cannabis sativa, require further investigation. Osteoarthritis (OA) is a chronic joint condition marked by gradual degradation of the cartilage and commonly associated with elevated levels of matrix metalloproteinases (MMPs). However, the influence of cannabiorcol on OA and its underlying mechanisms remains unclear. METHODS: In silico analysis investigated the key transcription factors that regulate MMP expression. A chondrocyte cell model [interleukin (IL)-1ß and IL-1⍺-treated C20A4 cell line] was established and treated with cannabiorcol. Associated cytotoxicity was assessed using a WST-8 assay. A monoiodoacetate-induced OA rat model was established and treated with cannabiorcol. Protein translocation and transactivation analyses were conducted using immunofluorescence and dual-luciferase reporter assays, respectively. Western blotting and real-time PCR analyzed relevant markers to examine cannabiorcol's effects on OA and its fundamental mechanisms. RESULTS: Cannabiorcol inhibits the expression of IL-1ß-induced MMPs compared to other cannabis-related compounds. In silico analysis revealed that the nuclear factor-kappa ß (NF-κß) and mitogen-activated protein kinase (MAPK) pathways are associated with MMP expression as key regulators. In vitro, cannabiorcol inhibits the NF-κB and p38 MAPK pathways independently cannabinoid receptors and transient receptor potential vanilloids. In vivo, cannabiorcol reduces MMP expression and ameliorates monoiodoacetate-induced OA traits in rats. CONCLUSION: Cannabiorcol inhibits IL-1ß-induced MMP expression in vitro and alleviates OA in an MIA-induced OA rat model by reducing MMP expression and inhibiting the p65/p38 axis.

Detection of foreign bodies in the canine stomach using capsule endoscopy: a randomized trial.

Introduction: This study aimed to assess the effectiveness of capsule endoscopy in detecting gastric foreign bodies in normal dogs, considering variations in the number of foreign bodies and the gastric environment. Methods: Five healthy male beagles were administered virtual, non-harmful foreign objects that maintained their shape in the stomach. Capsule endoscopy was performed and the images were evaluated by veterinarians and non-veterinarians. Results: The overall sensitivity and specificity of capsule endoscopy were 99.1 and 90.4%, respectively. Sensitivity and specificity were comparable between veterinarians and non-veterinarians. Sensitivity and specificity in the veterinarian group were 98.7 and 91.2%, respectively, whereas those in the non-veterinarian group were 100 and 88.5%, respectively. Discussion: Capsule endoscopy is a valuable alternative diagnostic tool for identifying foreign bodies in the stomach, particularly in challenging cases in which conventional imaging or invasive approaches have limitations.

Effect of Nurse's detection of neurological deterioration on the prognosis of patients with acute cerebral infarction.

Introduction: There is little evidence about the factors related to the detection of neurological deterioration by nurses. We examined the related factors and therapeutic outcomes of nurses' detections of patient's neurological deterioration. Methods: This was a descriptive retrospective study. We included 549 adult stroke patients who were admitted to the acute stroke unit of a tertiary hospital between May 2018 and December 2019 and had changes in neurological symptoms that were detected by stroke nurses. We measured the following outcomes: stroke lesion progression, early neurological deterioration (increase in the total national institutes of health stroke scale score of 2 points or more, increase in the limb weakness score of 1 point or more, or decrease in the alertness score of 1 point or more), and additional clinical management (increasing intravenous fluids, diagnostic imaging, or neuro-intervention). Data was analyzed by logistic regression. Results: A total of 651 new or aggravating symptoms were detected by nurses. The most detected symptom was motor aggravations (49.2 %). Symptoms were commonly detected during the day shift (51.0 %) and by scheduled neurochecks (71.3 %). Of 132 patients who underwent diagnostic imaging by nurses' detection, 63.6 % cases had stroke lesion progression. Nursing experience over 4 years was positively associated with finding stroke lesion progression (OR: 2.49, 95 % CI = 1.09-5.67). Early neurological deterioration was found in 70.7 %, and it was significantly higher during scheduled neurochecks (OR:2.65, 95 % CI = 1.04-6.72) and in the group of large artery atherosclerosis (OR: 2.19, 95 % CI = 1.06-4.49) Additional clinical management was provided to 49.9 % of detection, and scheduled neurocheks (OR: 4.76, 95 % CI = 2.18-10.39) and changes of alertness (OR: 2.89, 96 % CI = 1.51-5.26) were the significant factors. Conclusion: Stroke nurses were able to detect a large number of stroke lesion progression and early neurological deterioration as well as to provide additional clinical management. Systematic guidelines for qualification of stroke nurses may be beneficial.

Design and thermal-hydraulic analysis of multi-target system with 100 MeV proton linear accelerator for the production of 67Cu and 68Ge radioisotopes.

Radioisotopes are widely used in the fields of medicine, science, and industry. The growing demand for medical radioisotopes has driven research on alternative production methods. In particular, both isotopes of 67Cu and 68Ge play vital roles in the medical environment in many countries to be used in the radio-immunotherapy and the positron emission tomography imaging, respectively. This study designed a multi-target system consisting of two Zn and one Ga2O3 plates to enable simultaneous production of the medical radioisotopes 67Cu and 68Ge using 100 MeV proton beams. To understand the thermal effect on the multi-targets, we examined the distribution of energy absorbed in each solid plate target when exposed to an accelerated proton beam through the thermal-fluid analysis based on ANSYS simulation. For confirming thermal stability for two Zn targets and one Ga2O3 target, the modified water flow path inside the multi-target system was designed effectively with the controlled distribution of multiple sub-holes between main inlet and the following four channels. It was confirmed that the newly designed multi-target system of Zn and Ga2O3 solid plates shows higher thermal stability than the case of uniform distribution of water inlet, which means it could be exposed to a higher current beam of 7.57% to decrease the processing time.

Excessive Blood Pressure Rise and Cardiovascular Remodeling in Marathon Runners.

Exercise-induced hypertension (EIH) is thought to be associated with increased cardiovascular (CV) risks. However, no previous studies have investigated the effects of EIH on CV systems in marathon runners without CV risk factors using both 24-hr ambulatory blood pressure (BP) monitoring and exercise stress echocardiography (ESE). This study firstly described differences in CV adaptations according to EIH assessed by both exams. Marathon runners between 35 and 64 years of age without CV risk factors were eligible. All the participants underwent both 24-hr ambulatory BP monitoring and ESE. EIH was defined as a maximal exercise systolic BP≥210 mmHg. The EIH group (n=19) had shorter training history and higher exercise intensity compared to the non-EIH group (n=23). The average systolic BP was higher in the EIH group than in the non-EIH group. Left cardiac chamber size and left ventricular mass (LVM) were also higher in the EIH group compared to the non-EIH group. Maximal BP during ESE was positively correlated with both parameters. Exaggerated BP response during exercise needs to be monitored for pre-emptive measurements before it results in progressive cardiovascular maladaptation.

Possible Mechanisms for Adverse Cardiac Events Caused by Exercise-Induced Hypertension in Long-Distance Middle-Aged Runners: A Review.

Sudden cardiac death (SCD) is rare among athletes. However, hypertrophic cardiomyopathy is the leading cause of SCD among those <35 years of age. Meanwhile, coronary artery disease (CAD) is the primary SCD cause among those ≥35 years of age. CAD-induced plaque ruptures are believed to be a significant cause of cardiovascular diseases in middle-aged individuals who participate in extreme long-distance running activities such as marathons. A total of 1970 articles related to EIH were identified using search terms. Out of these, 1946 studies were excluded for reasons such as arterial hypertension, exercise-induced pulmonary hypertension, the absence of exercise stress testing (EST), and a lack of relevance to EIH. The study analyzed 24 studies related to both long-distance runners with exercise-induced hypertension (EIH) and the general public. Among these, 11 studies were quasi-experimentally designed studies used in randomized controlled trials (RCTs) on long-distance runners with EIH. Additionally, 12 studies utilized cohort designs, and one study with a quasi-experimental design was conducted among the general population. Recent studies suggest that an imbalance between oxygen demand and supply due to ventricular hypertrophy may be the actual cause of cardiovascular disease, regardless of CAD. Exercising excessively over an extended period can reduce endothelial function and increase arterial stiffness, which in turn increases afterload and leads to an excessive increase in blood pressure during exercise. Exercise-induced hypertension (EIH), which increases the morbidity rate of resting hypertension and is a risk factor for cardio-cerebro-vascular diseases, is more prevalent in middle-aged long-distance runners than in runners from other age groups, and it increases the prevalence of critical arrhythmias, such as atrial fibrillation or ventricular arrhythmias. EIH is associated with angiotensin II activity, and angiotensin II receptor blockers show promising effects in middle-aged runners. Further, guidelines for preventing excessive participation in races and restricting exercise intensity and frequency would be useful. This review identifies EIH as a potential risk factor for cardiovascular diseases and describes how EIH induces SCD.

Exercise-induced Hypertension and Carotid Intima-media Thickness in Male Marathon Runners.

This study aimed to identify the relationship between exercise-induced hypertension and carotid artery intima-media thickness in long-distance runners. Sixty healthy male runners aged 40 to 60 years were assigned to the following three groups based on resting blood pressure and maximal systolic blood pressure during a maximal exercise test: normal blood pressure response, exercise-induced hypertension, and complex hypertension. An exaggerated systolic blood pressure response was defined as a maximal systolic blood pressure+≥+210 mmHg during the maximal exercise test, while carotid intima-media thickness was measured using B-mode ultrasonography. The carotid intima-media thickness mean values were the highest in the complex hypertension group (0.72±0.11 mm), followed by exercise-induced hypertension (0.62±0.12 mm) and normal blood pressure groups (0.55±0.13 mm), with a significant difference between the groups (p+<+0.002). In linear regression analysis, the mean intima-media thickness was independently associated with age (p=0.015) and maximal systolic blood pressure (p=0.046) but not with resting systolic blood pressure. These results suggest that exercise-induced hypertension is associated with carotid intima-media thickness, a surrogate marker of cardiovascular disease, in long-distance runners. Therefore, evaluating the blood pressure response during exercise is important for the early detection of potential cardiovascular disease risks in long-distance runners.

Validation of the Korean Version of the Health Care Climate Questionnaire among Cancer Survivors.

Healthcare professionals should support autonomy in their patients in order for them to maintain the motivation to cope actively with their conditions. The Health Care Climate Questionnaire (HCCQ) is useful for assessing patients' perceptions of the autonomy support provided to them. We aimed to validate the psychometric properties of the Korean version of the HCCQ (HCCQ-K) among Korean cancer survivors. This study evaluated the factor structure, concurrent validity, and internal consistency. Data from 367 cancer survivors were analyzed using confirmatory factor analysis (CFA), Pearson's correlations, and Cronbach's α values. The CFA validated that the single-factor structure of the HCCQ-K had an excellent fit that was consistent with that of the original English version. Concurrent validity was confirmed by moderate correlations between the HCCQ-K and both psychological well-being and self-management. Reliability was verified by satisfactory internal consistency, with a Cronbach's α value of 0.91 and strong item-total and inter-item correlations. The HCCQ-K is therefore a valid and reliable tool for assessing autonomy support provided by healthcare professionals to Korean cancer survivors. The HCCQ-K may help healthcare professionals understand their patients' needs for autonomy support and develop strategies to motivate active coping behaviors.

Is wide excision really needed? Correlation between resection margin and recurrence in benign phyllodes tumors of the breast.

Purpose: Phyllodes tumors are similar to fibroadenomas in imaging and in pathological characteristics and are difficult to identify preoperatively. The purpose of this study was to analyze the recurrence rate after excision stratified by the surgical margin width and to propose and emphasize the "wait and watch" treatment strategy for benign phyllodes tumors. Methods: We performed a retrospective cohort study of patients diagnosed with benign phyllodes tumors by surgical excision between January 2000 and December 2022 at our institution. The medical and histopathological records were reviewed. Results: The results were obtained using the Cox proportional hazard regression and logistic regression. Resection margin status and recurrence were the independent variables. In each variable selection model, the resection margin was positive or less than 1 cm, and the recurrence rate was 3.7 and 1.04 times higher than the control group, but the difference was not statistically significant in 2 analyses. Conclusion: The surgical resection margin status of benign phyllodes tumors did not significantly affect locoregional recurrence. Therefore, follow-up imaging at short intervals without additional surgery is a feasible clinical option when the surgical resection margin is positive or less than 1 cm.

Photolithographic patterning on multi-wavelength quantum dot film of the improved conversion efficiency for digital holography.

A triple-wavelength patterned quantum dot film was fabricated for the light source of digital holography to improve both the axial measurement range and noise reduction. The patterned quantum dot film was fabricated after optimizing the photolithography process condition based on the UV-curable quantum dot solution, which was capable of multiple patterning processes. In addition, an optimized pattern structure was developed by adding TiO2 nanoparticles to both the quantum dot and bank layers to increase the scattering effect for the improved photoluminescence intensity. Finally, the newly developed light source with the balanced spectral distribution was applied to the digital holography, rendering it applicable as an improved light source.

Insampaedok-San Extract Exerts an Immune-Enhancing Effect through NF-κB p65 Pathway Activation.

Insampaedok-san (IS) has traditionally been prescribed as a medication for cold-related symptoms in Northeast Asia, including Korea and China. In this study, we focused on elucidating the molecular mechanism underlying the immunomodulatory activity of IS water extract (ISE) in macrophages. ISE significantly enhanced the levels of nitric oxide (NO) and prostaglandin E2 (PGE2) by increasing the expression of inducible NO synthase and cyclooxygenase-2 (COX-2) in a dose-dependent manner. ISE, which consists of many herbs, contains a large number of active compounds whose pharmacological targets and mechanisms are complicated. Therefore, network pharmacology analysis was used to predict the potential key components, targets, and mechanisms of ISE as immunomodulators. Subsequently, the network pharmacology results were validated experimentally. Seven key components were identified through HPLC-QTOF-MS. As predicted by the network pharmacology analysis, ISE increased the mRNA expression of Tnf and Il6. Furthermore, ISE increased the phosphorylation, nuclear translocation, and transcriptional activity of the p65 subunit of the nuclear factor-κB (NF-κB) signaling pathway. In contrast, rapamycin, an NF-κB inhibitor, suppressed the ISE-induced mRNA expression of Tnf and Il6. In conclusion, ISE is an immune activator that can elevate the production of NO, PGE2, and proinflammatory cytokines mediated by NF-κB signaling.

Cannabidiol Enhances Cabozantinib-Induced Apoptotic Cell Death via Phosphorylation of p53 Regulated by ER Stress in Hepatocellular Carcinoma.

Cannabidiol (CBD), a primary constituent in hemp and cannabis, exerts broad pharmacological effects against various diseases, including cancer. Additionally, cabozantinib, a potent multi-kinase inhibitor, has been approved for treating patients with advanced hepatocellular carcinoma (HCC). Recently, there has been an increase in research on combination therapy using cabozantinib to improve efficacy and safety when treating patients. Here, we investigated the effect of a combination treatment of cabozantinib and CBD on HCC cells. CBD treatment enhanced the sensitivity of HCC cells to cabozantinib-mediated anti-cancer activity by increasing cytotoxicity and apoptosis. Phospho-kinase array analysis demonstrated that the apoptotic effect of the combination treatment was mainly related to p53 phosphorylation regulated by endoplasmic reticulum (ER) stress when compared to other kinases. The inhibition of p53 expression and ER stress suppressed the apoptotic effect of the combination treatment, revealing no changes in the expression of Bax, Bcl-2, cleaved caspase-3, cleaved caspase-8, or cleaved caspase-9. Notably, the effect of the combination treatment was not associated with cannabinoid receptor 1 (CNR1) and the CNR2 signaling pathways. Our findings suggest that the combination therapy of cabozantinib and CBD provides therapeutic efficacy against HCC.

Grasping through dynamic weaving with entangled closed loops.

Pick-and-place is essential in diverse robotic applications for industries including manufacturing, and assembly. Soft grippers offer a cost-effective, and low-maintenance alternative for secure object grasping without complex sensing and control systems. However, their inherent softness normally limits payload capabilities and robustness to external disturbances, constraining their applications and hindering reliable performance. In this study, we propose a weaving-inspired grasping mechanism that substantially increases payload capacity while maintaining the use of soft and flexible materials. Drawing from weaving principles, we designed a flexible continuum structure featuring multiple closed-loop strips and employing a kirigami-inspired approach to enable the instantaneous and reversible creation of a woven configuration. The mechanical stability of the woven configuration offers exceptional loading capacity, while the softness of the gripper material ensures safe and adaptive interactions with objects. Experimental results show that the 130 g·f gripper can support up to 100 kg·f. Outperforming competitors in similar weight and softness domains, this breakthrough, enabled by the weaving principle, will broaden the scope of gripper applications to previously inaccessible or barely accessible fields, such as agriculture and logistics.

Examining the heterogeneity by employment status in dynamics between BMI and cognition: a longitudinal cohort study of the Korean aging population.

PURPOSE: This study investigated the potential heterogeneity by employment status in the relationship between body mass index (BMI) trajectory and cognitive function among an aging population. METHODS: We analyzed 2010-2018 cohort data from the Korean Longitudinal Study of Aging involving 4889 individuals aged over 45. We used statistical techniques of quadratic terms, interaction terms, time-invariant unobserved fixed effects, and time-lag effects to estimate the dynamic and interactive relationships among study variables. RESULTS: The effect of BMI on cognitive function was heterogeneous based on employment status. For the nonemployed group, the impact of BMI on cognitive function showed an inverted U-shape with a turning point (BMI 25); a higher BMI (up to 25) was associated with higher cognitive function, but further increases beyond this threshold led to decreased cognitive function. For the employed group, however, the impact of BMI on cognitive function was nonsignificant. The nonlinear effect of BMI on cognitive function for the nonemployed group was robust across various subgroups and specifications. CONCLUSIONS: The findings highlight the risk of obesity (BMI ≥ 25) on cognitive decline, particularly among nonemployed individuals. This illuminates the critical role of labor activity in regulating the impact of BMI on cognitive function among an aging population.

The Phytochemical Constituents of Medicinal Plants for the Treatment of Chronic Inflammation.

Prolonged exposure to inflammatory mediators can lead to tissue damage, fibrosis, angiogenesis, and altered cellular metabolism [...].

Harnessing a paper-folding mechanism for reconfigurable DNA origami.

The paper-folding mechanism has been widely adopted in building of reconfigurable macroscale systems because of its unique capabilities and advantages in programming variable shapes and stiffness into a structure1-5. However, it has barely been exploited in the construction of molecular-level systems owing to the lack of a suitable design principle, even though various dynamic structures based on DNA self-assembly6-9 have been developed10-23. Here we propose a method to harness the paper-folding mechanism to create reconfigurable DNA origami structures. The main idea is to build a reference, planar wireframe structure24 whose edges follow a crease pattern in paper folding so that it can be folded into various target shapes. We realized several paper-like folding and unfolding patterns using DNA strand displacement25 with high yield. Orthogonal folding, repeatable folding and unfolding, folding-based microRNA detection and fluorescence signal control were demonstrated. Stimuli-responsive folding and unfolding triggered by pH or light-source change were also possible. Moreover, by employing hierarchical assembly26 we could expand the design space and complexity of the paper-folding mechanism in a highly programmable manner. Because of its high programmability and scalability, we expect that the proposed paper-folding-based reconfiguration method will advance the development of complex molecular systems.

Gene Signatures and Associated Transcription Factors of Allergic Rhinitis: KLF4 Expression Is Associated with Immune Response.

This study is aimed at investigating the potential molecular features of allergic rhinitis (AR) and identifying gene signatures and related transcription factors using transcriptome analysis and in silico datasets. Transcriptome profiles were obtained using three independent cohorts (GSE101720, GSE19190, and GSE46171) comprising healthy controls (HC) and patients with AR. The pooled dataset (n = 82) was used to identify the critical signatures of AR compared with HC. Subsequently, key transcription factors were identified by a combined analysis using transcriptome and in silico datasets. Gene ontology: bioprocess (GO: BP) analysis using differentially expressed genes (DEGs) revealed that immune response-related genes were significantly enriched in AR compared with HC. Among them, IL1RL1, CD274, and CD44 were significantly higher in AR patients. We also identified key transcription factors between HC and AR using the in silico dataset and found that AR samples frequently express KLF transcription factor 4 (KLF4), which regulates immune response-related genes including IL1RL1, CD274, and CD44 in human nasal epithelial cells. Our integrative analysis of transcriptomic regulation provides new insights into AR, which may help in developing precision management for patients with AR.

The Impact of Light Wavelength and Darkness on Metabolite Profiling of Korean Ginseng: Evaluating Its Anti-Cancer Potential against MCF-7 and BV-2 Cell Lines.

Korean ginseng is a source of functional foods and medicines; however, its productivity is hindered by abiotic stress factors, such as light. This study investigated the impacts of darkness and different light wavelengths on the metabolomics and anti-cancer activity of ginseng extracts. Hydroponically-grown Korean ginseng was shifted to a light-emitting diodes (LEDs) chamber for blue-LED and darkness treatments, while white fluorescent (FL) light treatment was the control. MCF-7 breast cancer and lipopolysaccharide (LPS)-induced BV-2 microglial cells were used to determine chemo-preventive and neuroprotective potential. Overall, 53 significant primary metabolites were detected in the treated samples. The levels of ginsenosides Rb1, Rb2, Rc, Rd, and Re, as well as organic and amino acids, were significantly higher in the dark treatment, followed by blue-LED treatment and the FL control. The dark-treated ginseng extract significantly induced apoptotic signaling in MCF-7 cells and dose-dependently inhibited the NF-κB and MAP kinase pathways in LPS-induced BV-2 cells. Short-term dark treatment increased the content of Rd, Rc, Rb1, Rb2, and Re ginsenosides in ginseng extracts, which promoted apoptosis of MCF-7 cells and inhibition of the MAP kinase pathway in BV-2 microglial cells. These results indicate that the dark treatment might be effective in improving the pharmacological potential of ginseng.

Comparison of the differences in iron and anemia-related markers by ultramarathon distance.

BACKGROUND: Iron and anemia-related markers in long-distance runners have mostly been investigated following single distance marathons, with contradictory findings. This study compared iron and anemia-related markers according to marathon distance. METHODS: Iron and anemia-related markers were analyzed from blood samples of healthy, adult male (aged ≥40-60 years) long-distance runners before and after ultramarathon races of 100 km (N.=14), 308 km (N.=14), and 622 km (N.=10). Fe, total iron-binding capacity (TIBC), unsaturated iron-binding capacity (UIBC), transferrin saturation, ferritin, high-sensitivity C-reactive protein (hs-CRP), white blood cell (WBC), red blood cell (RBC), hemoglobin (Hb), and hematocrit (Hct) levels were analyzed. RESULTS: On completion of all races, the iron levels and transferrin saturation decreased (P<0.05), while the ferritin and hs-CRP levels and WBC counts significantly increased (P<0.05). The Hb concentrations increased after the 100-km race (P<0.05), although the Hb levels and Hct decreased after the 308- and 622-km races (P<0.05). The highest-to-lowest levels of unsaturated iron-binding capacity were found following the 100-km, 622-km, and 308-km races, whereas those of the RBC count were found following the 622-km, 100-km, and 308-km races. Ferritin levels were significantly higher following the 308-km race than after the 100-km race (P<0.05); hs-CRP levels in the 308- and 622-km races were higher than those in the 100-km race. CONCLUSIONS: Ferritin levels increased due to inflammation following distance races, and runners experienced transient iron deficiency without anemia. However, the differences in iron and anemia-related markers according to the ultramarathon distance remain unclear.

The efficient synthesis and biological evaluation of justicidin B.

A facile new synthetic method for the preparation of a Type-A 1-arylnaphthalene lactone skeleton was developed and used to synthesise justicidin B and several derivatives. Key synthesis steps included Hauser-Kraus annulation of a phthalide intermediate and Suzuki-Miyaura cross coupling between a triflated naphthalene lactone intermediate and various potassium organotrifluoroborates. With two exceptions, the derivatives showed significant inhibitory effect on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse macrophages. Moreover, several compounds, including justicidin B, had marked cytotoxicity towards six human tumour cell lines.