Vascular endothelial growth factor (VEGF) is well recognized as an essential component of angiogenesis and the increased proliferation and migration of endothelial cells. Bone marrow-derived ...endothelial progenitor cells (EPCs) are involved in VEGF-induced vessel formation during physiological and pathological states. Soya-cerebroside, an extract from Cordyceps militaris, reduces synovial inflammation and prevents cartilage damage in an osteoarthritis model. However, the role of soya-cerebroside in VEGF-regulated EPC angiogenesis is uncertain. Records from the Oncomine database demonstrate higher levels of VEGF in cancerous tissue compared with normal tissue. This study describes VEGF-induced promotion of EPC-associated angiogenesis in vivo and how the treatment of EPCs with soya-cerebroside inhibited VEGF-facilitated migration and tube formation. The study evidence shows that the c-Src, FAK and Runx2 signalling pathways are involved in the inhibitory effects of soya-cerebroside. This novel agent may therefore be used to inhibit EPC-associated angiogenesis.
This retrospective cohort study investigated the risk of major bleeding events during the concurrent use of Chinese herbal medicine (CHM) and anticoagulants in clinical practice. A total of 4,470 ...patients receiving anticoagulant drugs were selected from Taiwan's National Health Insurance Research Database (NHIRD). Half (n = 2,235) were also using CHMs (CHM cohort); the other half were not (non-CHM cohort). Each cohort was matched 1:1 using the propensity score. Chi-square testing and the Student's t-test were used to examine differences between two cohorts. Cox proportional hazard regression analysis assessed the risks for major bleeding events in each cohort, as well as bleeding risks associated with specific CHM formulas and herbs. Cumulative incidence curves for major bleeding events were calculated using Kaplan-Meier analysis. Compared with the non-CHM cohort, the CHM cohort had a lower risk of overall bleeding events (p < 0.001) including hemorrhagic stroke (p = 0.008), gastrointestinal (GI) bleeding (p < 0.001), urogenital bleeding (p less than or equal to 0.001) and nasal/ear/eye bleeding (p = 0.004). Single herbs, such as Glycyrrhiza uralensis et Rhizoma, Panax notoginseng, Panax ginseng, Platycodon grandiflorum, Eucommia ulmoides Oliver and formulas, such as Shu Jing Huo Xue Tang, Shao Yao Gan Cao Tang and Ji Sheng Shen Qi Wan were associated with a lower risk of major bleeding events. Using CHMs with anticoagulants appeared to decrease the risk of major bleeding, especially CHMs products containing Glycyrrhiza uralensis et Rhizoma, Panax notoginseng, Panax ginseng, Platycodon grandiflorum and Eucommia ulmoides Oliver. Further investigations are needed to determine whether CHM can maintain the therapeutic efficacy of anticoagulants while simultaneously reducing potential side effects.
The recruitment of bone marrow-derived endothelial progenitor cells (EPCs) facilitates physiological and pathological processes involved in new blood vessel synthesis. Glucocerebroside, an extract of ...Cordyceps militaris, inhibits inflammatory cytokine production and monocyte migration, although its anti-angiogenic properties in human EPCs has remained largely unknown up until now. We describe how glucocerebroside reduces migration as well as tube formation induced by vascular endothelial growth factor (VEGF) stimulation in human EPCs, without affecting cell viability. This inhibitory effect was achieved through the focal adhesion kinase (FAK)/c-Src pathways. We also found that glucocerebroside reduced VEGF-promoted upregulation of the transcription factor Runx2 in the EPCs. The in vivo chick embryo chorioallantoic membrane model demonstrated that glucocerebroside reduces new vessel formation. Our investigation is the first to show that glucocerebroside reduces angiogenesis in human EPCs and to describe the underlying mechanisms. Further investigations are needed to examine the effects of glucocerebroside in other angiogenesis-related disorders.
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•Plumbagin does not affect the cell viability of human EPCs.•Plumbagin suppresses VEGF-promoted EPC migration and tube formation.•Plumbagin reduces VEGF-induced promotion of PLC, Akt ...and ERK activation.•Plumbagin inhibits VEGF-induced promotion of NF-κB and HIF-1 activation in EPCs.•Plumbagin suppress EPC expression and angiogenesis in vivo.
Plumbagin, a naturally occurring naphthoquinone component isolated from the root of Plumbago zeylanica, reduces angiogenesis in human umbilical vein endothelial cells; whether plumbagin also has anti-angiogenic activity in human endothelial progenitor cells (EPCs) has remained unclear. Importantly, the recruitment of bone marrow-derived EPCs promotes physiological and pathological neovascularization. In this study, plumbagin inhibited vascular endothelial growth factor (VEGF)-induced migration and tube formation of human EPCs, without cytotoxic effects. We also found that plumbagin inhibited angiogenesis via the phospholipase C (PLC), Akt, extracellular-signal-regulated kinase (ERK), nuclear factor (NF)-κB and hypoxia-inducible factor (HIF)-1 signaling pathways. In an EPC Matrigel plug assay, plumbagin significantly diminished microvessel formation and EPC-specific marker expression. Our report is the first to reveal that plumbagin reduces EPC-related angiogenesis both in vitro and in vivo. Further evaluations of plumbagin are warranted, to determine its antitumor activity and other angiogenesis-related disorders.
YKL-40, also known as human cartilage glycoprotein-39 or chitinase-3-like-1, is a pro-inflammatory protein that is highly expressed in rheumatoid arthritis (RA) patients. Angiogenesis is a critical ...step in the pathogenesis of RA, promoting the infiltration of inflammatory cells into joints and providing oxygen and nutrients to RA pannus. In this study, we examined the effects of YKL-40 in the production of the pro-inflammatory cytokine interleukin-18 (IL-18), and the stimulation of angiogenesis and accumulation of osteoblasts. We observed that YKL-40 induces IL-18 production in osteoblasts and thereby stimulates angiogenesis of endothelial progenitor cells (EPCs). We found that this process occurs through the suppression of miR-590-3p via the focal adhesion kinase (FAK)/PI3K/Akt signaling pathway. YKL-40 inhibition reduced angiogenesis in in vivo models of angiogenesis: the chick embryo chorioallantoic membrane (CAM) and Matrigel plug models. We report that YKL-40 stimulates IL-18 expression in osteoblasts and facilitates EPC angiogenesis.
Purpose: Fu’s subcutaneous needling (FSN) is a new acupuncture technique that produces a long-lasting effect in soft-tissue injuries. In patients with degenerative knee osteoarthritis (OA), ...myofascial trigger points (MTrPs) are common in the lower-limb muscles. In this randomized clinical trial, we evaluated the immediate, 1-week and 2-week effectiveness of FSN therapy in the treatment of degenerative knee OA. Patients and methods: We randomly divided 32 patients with knee OA into the FSN group (mean age: 65.73 ± 6.79 years) or the transcutaneous electrical nerve stimulation (TENS) group (mean age: 62.81 ± 5.72 years). The pressure pain threshold (PPT) and tissue hardness (TH) of the muscle and tendon attachment sites, knee range of motion, and physical ability (average walking speed) were measured. The subjective pain intensity index, Western Ontario and McMaster Universities OA Index (WOMAC), and Lequesne index were used to determine the efficacy of FSN on MTrP-induced soft-tissue pain compared with that of TENS. Results: A significantly greater improvement in pain qualities in the VAS (p < 0.05) was found in the FSN group. Moreover, in muscle and tendon qualities (including PPT and TH), a significant difference in the PPT of the quadriceps muscle (p < 0.05) was also observed among the immediate treatments in the FSN group. As for the functional index questionnaire assessment, the FSN group exhibited significant improvements among the immediate, 1-week and 2-week efficacies in terms of WOMAC (p < 0.05) and Lequesne index scores (p < 0.05). Conclusion: FSN was effective in treating soft-tissue pain in degenerative knee OA in terms of alleviating pain, strengthening walking ability, and improving overall functional performance. Pain relief was the primary benefit of FSN and a significant correlation between pain relief and knee joint mobility improvement was found. Trial registration: ClinicalTrials.gov Protocol Registration and Results System (registration number: NCT04356651).
Rheumatoid arthritis (RA) is characterised by the infiltration of a number of proinflammatory cytokines into synovial fluid. Soya-cerebroside, an extract from Cordyceps militaris, inhibits synovial ...inflammation and reduces cartilage damage in an osteoarthritis model, although the role of soya-cerebroside in inflammatory cytokine expression in RA is uncertain. In this study, Gene Expression Omnibus (GEO) database records revealed higher levels of interleukin (IL)-1β, IL-6 and IL-8 in RA tissue compared with normal tissue. Elevated levels of these inflammatory cytokines were also higher in mice with collagen-induced arthritis (CIA) than in control mice. Soya-cerebroside effectively inhibited IL-1β, IL-6 and IL-8 expression in RA synovial fibroblasts, apparently by inhibiting the ERK, NF-κB and AP-1 signalling pathways. This anti-inflammatory agent shows promise for the treatment of RA.
This study aims to explore the effects of noise and music types on nurses' anxiety, mental workload and situation awareness during an operation. Participants included 20 circulating nurses (CNs) and ...16 nurse anesthetists (NAs) who completed a total of 70 operations in which each operation required one CN and one NA. The experiment was separated into a control group (operating noise only) vs. an experimental group (3 different music types-between subjects and 2 music volume levels-within-subjects). Results showed that all participants had excellent situation awareness performance despite their mental workload showing significant differences in various phases of the surgery. Music at 55–60 dB caused lower mental workloads and anxiousness for nurses than those exposed to levels of 75–80 dB. When Mozart's music was played, the participants' mental workload and situation anxiety were lower than when exposed to other music types. Music played at 60 dB during an operation may be a feasible solution to mitigate the negative effects of extra noise and thus improve the nurses' performance.
•Noise exposure and music impact the effectiveness of the operation and patient safety.•Sound level exhibited a significant effect on the mental workload and anxiety of nurses.•The nurses' SWAT scores and STAI-S scores were positively correlated.•However, the nurses' SA remained unaffected and kept in excellent levels.•Mozart music set at 60 dB during the operation could improve the nurses' performance.
In Taiwan, lung cancer remains one of the deadliest cancers. Survival of lung cancer patients remains low, ranging from 6% to 18%. Studies have shown that Chinese herbal medicine (CHM) can be used to ...induce cell apoptosis and exhibit anti-inflammatoryanti-inflammatory activities in cancer cells.
This study aimed to investigate the frequencies and patterns of CHM treatment for lung cancer patients and the effect of CHM on their survival probability in Taiwan.
We identified 6939 lung cancer patients (ICD-9-CM: 162). We allocated 264 CHM users and 528 CHM-non users, matched for age, gender, duration, and regular treatment. Chi-square test, conditional multivariable logistic regression, Kaplan-Meier method, and the log-rank test were used in this study.
The CHM group was characterized by a longer follow up time and more cases of hyperlipidemia and liver cirrhosis. This group exhibited a lower mortality hazard ratio (0.48, 95% confidence interval 0.39–0.61, p < 0.001), after adjusting for comorbidities. The trend was also observed that the cumulative survival probability was higher in CHM than in non-CHM users (p < 0.0001, log rank test). Analysis of their CHM prescription pattern revealed that Bu-Zhong-Yi-Qi-Tang (BZYQT), Xiang-Sha-Liu-Jun-Zi-Tang (XSLJZT), and Bai-He-Gu-Jin-Tang (BHGJT); and Bei-Mu (BM), Xing-Ren (XR) and Ge-Gen (GG) were found to be the top three formulas and herbs, respectively. Among them, BM was the core CHM of the major cluster, and Jie-Geng (JG) and Mai-Men-Dong-Tang (MMDT) were important CHMs by CHM network analysis.
The use of CHM as an adjunctive therapy may reduce the mortality hazard ratio of lung cancer patients. The investigation of their comprehensive CHM prescription patterns might be useful in future large-scale, randomized clinical investigations of agent effectiveness, safety, and potential interactions with conventional treatments for lung cancer patients.
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Chondrosarcoma is a type of highly malignant tumor with a potent capacity for local invasion and causing distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. ...Hepatocyte growth factor (HGF) has been demonstrated to stimulate cancer proliferation, migration, and metastasis. However, the effect of HGF on migration activity of human chondrosarcoma cells is not well known. Here, we found that human chondrosarcoma tissues demonstrated significant expression of HGF, which was higher than that in normal cartilage. We also found that HGF increased the migration and expression of matrix metalloproteinase (MMP)-2 in human chondrosarcoma cells. c-Met inhibitor and siRNA reduced HGF-increased cell migration and MMP-2 expression. HGF treatment resulted in activation of the phosphatidylinositol 3'-kinase (PI3K)/Akt/PKCδ/NF-κB pathway, and HGF-induced expression of MMP-2 and cell migration was inhibited by specific inhibitors or siRNA-knockdown of PI3K, Akt, PKCδ, and NF-κB cascades. Taken together, our results indicated that HGF enhances migration of chondrosarcoma cells by increasing MMP-2 expression through the c-Met receptor/PI3K/Akt/PKCδ/NF-κB signal transduction pathway.
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