Traditional Banxia Xiexin decoction inhibits invasion, metastasis, and epithelial mesenchymal transition in gastric cancer by reducing lncRNA TUC338 expression.

Background: Banxia Xiexin decoction (BXD) is a classic traditional Chinese medicine (TCM) formula clinically used to treat chronic gastritis, gastric ulcers, gastric cancer, and many other gastrointestinal diseases. Long noncoding RNAs (lncRNAs) have been shown to play an important role in maintaining the malignant phenotype of tumors. However, no relevant studies have shown whether Banxia Xiexin decoction regulates and controls lncRNA TUC338, and the effect of TUC338 on the regulation of gastric cancer invasion and metastasis remains unclear. Purpose: To investigate the ability of the traditional Chinese medicine (TCM) Banxia Xiexin decoction (BXD) to inhibit the migration and invasion of human gastric cancer AGS cells by regulating the long noncoding RNA (lncRNA) TUC338. Methods: UHPLC‒MS/MS was used to analyze the chemical components of BXD. MTT was performed to determine the effects of BXD on the proliferation of AGS cells. qRT‒PCR was used to determine the expression of lncRNA TUC338 in gastric cancer tissues, paracarcinoma tissues, AGS human gastric cancer cells and GES-1 normal gastric mucosa cells and to evaluate the effects of BXD on the expression of lncRNA TUC338 in AGS cells. Lentiviral transfection was used to establish human gastric cancer AGS cells with knocked down lncRNA TUC338 expression. The effects of lncRNA TUC338 knockdown on the migration and invasion of AGS cells were observed by a scratch assay and Transwell migration assay, respectively. Western blotting was performed to analyze the effects of lncRNA TUC338 knockdown on epithelial-to-mesenchymal transition (EMT) in AGS cells. We performed quality control on three batches of BXD. We used UHPLC‒MS/MS to control the quality of three random batches of BXD used throughout the study. Results: Ninety-five chemical components were identified from the water extract of BXD, some of which have anticancer effects. The expression of TUC.338 in gastric cancer tissues was higher than that in para-carcinoma tissues. BXD inhibited the invasion and migration of gastric cancer cells by inhibiting the expression of lncRNA TUC338, which reduced EMT. After knockdown of lncRNA TUC338, the migration and invasion of AGS cells were reduced; the expression of the EMT-related protein E-cadherin was increased, and the expression of N-cadherin and vimentin was reduced. Conclusions: The present results suggest that BXD has potential as an effective treatment for gastric cancer through the inhibition of lncRNA TUC338 expression.

Sitagliptin mitigates hypoxia/reoxygenation (H/R)-induced injury in cardiomyocytes by mediating sirtuin 3 (SIRT3) and autophagy.

Potential ischemia/reperfusion (I/R) injuries are commonly induced during treatment of cardiovascular diseases, such as acute myocardial infarction (AMI). It is reported that oxidative stress and over-autophagy in cardiomyocytes are involved in the pathogenesis of I/R injury. Sitagliptin is an effective inhibitor of dipeptidyl peptidase 4 (DPP-4) for the treatment of diabetes, which is recently reported to regulate oxidative stress and autophagy. The present study is designed to explore the function of Sitagliptin on I/R injury. Hypoxia/reoxygenation (H/R) condition was used to simulate the I/R injury on cardiomyocytes. We found that the declined cell viability and elevated expression level of creatine kinase myocardial band (CK-MB) were observed in the H/R group, accompanied by the increased mitochondrial reactive oxygen species (ROS), elevated cellular malondialdehyde (MDA) level, and mitochondrial dysfunction. After Sitagliptin treatment, the damages in H9c2 cardiomyocytes, oxidative stress, and mitochondrial dysfunction were significantly alleviated. In addition, the overactivated autophagy and mitophagy in H/R-challenged cardiomyocytes were dramatically mitigated by Sitagliptin, accompanied by the upregulation of SIRT3. Lastly, the protective effect of Sitagliptin on H/R-induced mitophagy, autophagy, and damages in cardiomyocytes was dramatically abolished by the knockdown of SIRT3. Taken together, our data reveal that Sitagliptin ameliorated the H/R-induced injury in cardiomyocytes by mediating sirtuin 3 (SIRT3) and autophagy.

Atractylenolide I Inhibits NLRP3 Inflammasome Activation in Colitis-Associated Colorectal Cancer via Suppressing Drp1-Mediated Mitochondrial Fission.

Inflammatory bowel disease (IBD) is an important high-risk factor that promotes the occurrence and development of colon cancer. Research on the mechanism of regulating NLRP3 can provide potential targets for treating NLRP3 inflammasome-related diseases and changing the inflammatory potential of immune cells. In this study, the effects of atractylenolide I on colitis-associated CRC (caCRC) and inflammasome activation were investigated both in vivo and in vitro. Furthermore, the role of atractylenolide I on Drp1-mediated mitochondrial fission was analyzed via Western blotting and transmission electron microscopy (TEM). Moreover, the Drp1 overexpression lentiviral vector was used to study the role of Drp1 on the signaling mechanisms of atractylenolide I. Atractylenolide I treatment significantly reduced the cell viability of human HCT116 and SW480 cells and induced apoptosis, and effectively inhibited colon tumors in the AOM/DSS mouse model. The reduction of NLRP3 inflammasome activation and excessive fission of mitochondria mediated by Drp1 were associated with the administration of atractylenolide I. Upregulation of Drp1 reversed the inhibitory effect of atractylenolide I on the activation of NLRP3 inflammasomes. Overexpressing the Drp1 expression counteracted the restraint of atractylenolide I on the release of IL-1ß of LPS/DSS-stimulated BMDMs. Atractylenolide I inhibited NLRP3 and caspase-1 expression in mice BMDMs, with no influence in the Drp1-overexpressed BMDMs. These results demonstrated that atractylenolide I inhibits NLRP3 inflammasome activation in colitis-associated colorectal cancer via suppressing Drp1-mediated mitochondrial fission.

Greenway Cyclists' Visual Perception and Landscape Imagery Assessment.

Greenway is a kind of corridors in the city that takes natural elements as the main constituent foundation and connects open spaces with functions such as leisure and recreation. The assessment of the built greenway is a review of the past construction experiences, and it is also a supplement and improvement to the future greenway planning concept system, which has important academic and application value. This study will explore how greenway design factors influenced the local cyclists' perception of the landscape using on-site questionnaire and photo rating method. The results indicated that greenways with continuous cycling paths, high security awareness, open landscapes, and rich human activities evoke positive perceptions. Among the visual elements, natural elements such as plants and sky are more favorable than artificial elements. The research results show that the formation of greenway cyclists' landscape imagery is affected by visual perception elements, which suggests that special consideration should be given to the laws of cyclists' mental perception when designing greenways.

Metabolomic Study on the Therapeutic Effect of the Jianpi Yangzheng Xiaozheng Decoction on Gastric Cancer Treated with Chemotherapy Based on GC-TOFMS Analysis.

OBJECTIVE: This study aimed to find new biomarkers of prognosis and metabolomic therapy for gastric carcinoma (GC) treated with chemotherapy and investigate the metabolic mechanism of the Jianpi Yangzheng Xiaozheng (JPYZXZ) decoction in the treatment of GC. METHODS: First, 36 patients with GC were randomly assigned to the treatment (chemotherapy plus JPYZXZ) and control (chemotherapy alone) groups. The clinical efficacy, side effects, and quality of life of patients in the two groups were evaluated after treatment. Then, the serum samples taken from 16 randomly selected patients (eight treatment cases and eight control cases with no evident pattern characters) and eight healthy volunteers were tested to identify the differential metabolite under the gas chromatography-time-of-fight mass spectrometry platform. The relevant metabolic pathways of differential substances were analyzed using multidimensional statistical analysis. RESULTS: JPYZXZ combined with chemotherapy resulted in a lower risk of leucopenia, thrombocytopenia, and gastrointestinal reaction (P < 0.05). Additionally, patients in the treatment group showed a higher Karnofsky (KPS) scale (P < 0.05). Compared with healthy persons, patients with GC were found to have 26 significant differential metabolites after chemotherapy; these metabolites are mainly involved in 12 metabolic pathways, such as valine, leucine, and isoleucine biosynthesis. JPYZXZ primarily influences the pentose phosphate pathway; glutathione metabolism; glyoxylate and dicarboxylate metabolism; porphyrin and chlorophyll metabolism; and glycine, serine, and threonine metabolism of patients with GC treated with chemotherapy. CONCLUSIONS: The metabolic characteristics of patients with GC after chemotherapy are mainly various amino acid metabolic defects, especially L-glutamine, L-leucine, L-alloisoleucine, and L-valine. These defects lead to a series of problems, such as decreased tolerance and effectiveness of chemotherapy, increased side effects, decreased immunity, and shortened survival time. In addition, the remarkable upregulation of the gluconolactone level in patients with GC suggests the high proliferative activity of GC cells. Thus, gluconolactone may be used as a potential prognostic and diagnostic evaluation index. Moreover, JPYZXZ can reduce the incidence of ADRs and improve the life quality of patients by the correction of L-glutamine, L-leucine, L-alloisoleucine, and L-valine metabolism deficiency. In addition, gluconolactone metabolism is inhibited by JPYZXZ. Such inhibition may be one of the antitumor mechanisms of JPYZXZ.

Curculigoside attenuates oxidative stress and osteoclastogenesis via modulating Nrf2/NF-κB signaling pathway in RAW264.7 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Curculigo orchioides Gaertn is used for the treatment of impotence, atrophic debility of bones (osteoporosis), limb limpness, and arthritis of the lumbar and knee joints in traditional Chinese medicine and Ayurvedic medical system. Curculigoside (Cur) from Curculigo orchioides Gaertn has been shown to have regulatory effects on bone metabolism via anti-oxidative activities in rats and osteoblasts. However, little is known about the molecular pharmacological activity of Cur in osteoclastic bone resorption. AIM: The aim of this work is to investigate the inhibitory effect of Cur against osteoclasts (OCs) under the oxidative stress status, and explore the possible underlying mechanism. MATERIALS AND METHODS: OCs were induced from RAW264.7 cells using RANKL and H2O2. The number of OCs was measured by tartrate-resistant acid phosphatase (TRAP) staining. F-Actin and nuclear translocation of P65 and Nrf2 were stained with immunofluorescence assay and observed under a laser confocal microscope. The biochemical parameters of OCs were detected with an ELISA kit. The expression of Nrf2 and NF-κB pathway-related proteins was analyzed by Western Blot. RESULTS: Cur inhibited the TRAP activity, release of degrading products from bone slices and the expression of NFATc1, c-Fos, Cathepsin K (Ctsk) and matrix metallopeptidase 9 (MMP9) of OCs induced with RANKL and H2O2. In addition, Cur suppressed the ROS level and NADPH oxidase 1(NOX1) and NADPH oxidase 4 (NOX4) activities of OCS. More importantly, Cur enhanced the expression and nucleus translocation of Nrf2 and activities of its regulatory cytoprotective enzymes, and reduced the NF-κB expression and phosphorylation and nucleus translocation of p65 in OCs. Furthermore, the Nrf2 inhibitor ML385 and NF-κB inhibitor Bay11-7082 counteracted the effect of Cur in OCs. CONCLUSION: Cur mitigated oxidative stress and osteoclastogenesis by activating Nrf2 and inhibiting the NF-κB pathway, suggesting that Cur may prove to be a promising candidate for the treatment of osteoporosis. Our findings may also help partially explain the rationale behind the traditional use of Curculigo orchioides Gaertn.

Associations Between Built Environment Characteristics and Walking in Older Adults in a High-Density City: A Study From a Chinese Megacity.

The built environment is an important factor affecting physical activity, especially walkability. Walkability is used to characterize the user friendliness of outdoor physical activity. However, studies on walkability and physical activity are mainly concentrated on low-density Western cities. Study on the walkability of high-density cities in Asia, especially with the elderly, is seriously lacking. And walkability is often used as a composite indicator. This study mainly re-examines the relationship between the common indicators of walkability (population density, street connectivity, land-use mix, and retail density), transport-related walking, and leisure-time walking with older adults in China's megacities. Twelve housing estates in Wuhan were selected for study areas. We explored the association between the walking activities of 1,161 elderly people (≥60 years old) and the indicators of walkability in their neighborhoods. Socio-demographic characteristics were controlled in the multilevel logistic regression models of the built environment walking associations. We found that there was no significant correlation between the four indicators of walkability and transport-related walking. Street connectivity is significantly positively correlated with the participants' leisure-time walking (OR = 1.499, 95% CI = 1.068~2.103), and there was no significant correlation between the other indicator of walkability and leisure-time walking. The results show that there was no statistical correlation between walkability and transport-related walking in the elderly, and only one indicator was related to leisure-time walking. It is extremely important to re-examine the characteristics of built environments and elderly walking activities in high-density cities. Only by implementing effective intervention strategies in different urban backgrounds can cities move toward a more active and healthier path.

Prevention of ventricular arrhythmia complicating acute myocardial infarction by local cardiac denervation.

BACKGROUND: Augmentation of sympathetic nerve activity after acute myocardial infarction (AMI) contributes to fatal arrhythmia. In this study, we investigated whether local ablation of the coronary sinus (CS) and great cardiac vein (GCV) peripheral nerves could reduce ventricular arrhythmias (VA) in a canine AMI model. METHODS: Twenty-one anesthetized dogs were randomly assigned into the sham-operated, MI and MI-ablation groups, respectively. The incidence and duration of VA were monitored among different groups. The ventricular effective refractory period (ERP), the ERP dispersion and the ventricular fibrillation threshold (VFT) were measured during the experiments. Norepinephrine (NE) levels in CS blood and cardiac tissue were also detected in this study. RESULTS: The incidence and duration of VA in MI-ablation group were significantly reduced as compared to the MI dogs (p<0.05). Furthermore, local cardiac denervation drastically prolonged the ventricular ERP in the ischemia area, decreased the ERP dispersion, and reduced NE levels in CS blood (P<0.05). VFT also showed an increased trend in the AMI-ablation group. CONCLUSIONS: The results of this study indicate that, in the canine AMI model, local ablation of CS and GCV peripheral nerves reduces VA occurrence and improves ventricular electrical stability with no obvious effects on heart rate, mean arterial pressure and infarct size. This study suggests that local cardiac denervation may prevent ventricular arrhythmias complicating AMI.

Assessment of atrial fibrillation and vulnerability in patients with Wolff-Parkinson-White syndrome using two-dimensional speckle tracking echocardiography.

PURPOSE: The aim was to assess atrial fibrillation (AF) and vulnerability in Wolff-Parkinson-White (WPW) syndrome patients using two-dimensional speckle tracking echocardiography (2D-STE). METHODS: All patients were examined via transthoracic echocardiography and 2D-STE in order to assess atrial function 7 days before and 10 days after RF catheter ablation. A postoperative 3-month follow-up was performed via outpatient visit or telephone calls. RESULTS: Results showed significant differences in both body mass index (BMI) and supraventricular tachycardia (SVT) duration between WPW patients and DAVNP patients (both P<0.05). Echocardiography revealed that the maximum left atrial volume (LAVmax) and the left ventricular mass index (LVMI) in diastole increased noticeably in patients with WPW compared to patients with DAVNP both before and after ablation (all P<0.05). Before ablation, there were obvious differences in the levels of SRs, SRe, and SRa from the 4-chamber view (LA) in the WPW patients group compared with patients in the DAVNP group (all P<0.05). In the AF group, there were significant differences in the levels of systolic strain rate (SRs), early diastolic strain rate (SRe), and late diastolic strain rate (SRa) from the 4-chamber view (LA) both before and after ablation (all P<0.05). In the non-AF group, there were decreased SRe levels from the 4-chamber view (LA/RA) pre-ablation compared to post-ablation (all P<0.05). CONCLUSION: Our findings provide convincing evidence that WPW syndrome may result in increased atrial vulnerability and contribute to the development of AF. Further, RF catheter ablation of AAV pathway can potentially improve atrial function in WPW syndrome patients. Two-dimensional speckle tracking echocardiography imaging in WPW patients would be necessary in the evaluation and improvement of the overall function of RF catheter ablation in a long-term follow-up period.

The effect of B-type brain natriuretic peptide on patients with acute decompensated heart failure coexisting with lung cancer: a randomized controlled clinical trial.

Congestive heart failure (CHF) as a common comorbidity in patients with lung cancer, especially those of old age. The tumor combined with heart failure makes the reasons of dyspnea more complicated and effective drugs to improve symptoms are urgently needed. Recombinant human B-type natriuretic peptide (rhBNP) is a member of the natriuretic peptide family that exerts cardiovascular effects. The major goal of this study was to study the effect of rhBNP on patients with decompensated heart failure coexisted with lung cancer. Emergency decompensated HF patients with lung cancer admitted for dyspnea were randomly assigned to open label therapy with standard treatment (control group) or standard treatment + rhBNP(rhBNP group) for up to 7 days. Then we recorded the changes of symptoms, examined and followed up every 3 months to evaluate the effect of rhBNP on decompensated heart failure patients with lung cancer. We found that dyspnea, fatigue and edema of lower extremity were significantly improved in the rhBNP group compared to the control group after 7 days of treatment. Survival rate was not significantly different in the mean 18.4 +/- 8.6 months of follow-up. Results from our study suggested that rhBNP significantly improved symptoms in emergency decompensated HF patients with lung cancer admitted for dyspnea in the short-term, but did not improve survival rate in the long-term.

[Relationship between plasma asymmetrical dimethylarginine and coronary artery disease].

OBJECTIVE: To investigate whether the plasma asymmetrical dimethylarginine (ADMA) level correlates with the extent and severity of coronary atherosclerosis. METHODS: 110 consecutive patients undergoing coronary angiography were divided into five groups according to the result thereof: control group (n = 22, with normal coronary artery), mild coronary artery disease (CAD) group (n = 21, with stenosis < 50% of the major coronary arteries), single branch CAD group III (n = 22, with stenosis >/= 50% of one major coronary artery); double branch CAD group IV (n = 23, with stenosis >/= 50% of two major coronary arteries); and multi-branch CAD group (n = 22, with significant stenosis >/= 50% of more than two major coronary arteries or companies with stenosis of left major coronary). ELISA was used to detect the plasma ADMA. Nitric acid reductase method and colorimetry were used to measure the levels of plasma nitric oxide (NO) and nitrogen oxide synthase (NOS). The relationship between the plasma ADMA and severity of CAD was analyzed. RESULTS: The plasma ADMA levels of in last three a groups were 1.52 micromol/L +/- 0.61 micromol/L, 1.67 micromol/L +/- 0.80 micromol/L, and 2.60 micromol/L +/- 0.62 micromol/L all significantly higher than that of the control group (0.79 micromol/L +/- 0.54 micromol/L, P < 0.01). The plasma NO and NOS levels of the multi-branch CAD group were significantly lower than those of the other groups (all P < 0.01), and there were not significant differences in Plasma NO and NOS levels among the other groups. Multivariate stepwise logistic regression analysis showed that the plasma ADMA level was significantly positively correlated with the severity of coronary atherosclerosis (r = 0.684, P = 0.007) and total cholesterol and triglyceride (r = 0.623 and 0.536 respectively), and significantly negatively correlated with the NO and NOS levels (r = -0.709 and -0.701 respectively). CONCLUSION: Correlated significantly with the severity of coronary atherosclerosis, the plasma ADMA level may become a novel marker of CAD.

[The relationship between the levels of lysophosphatidic acid and left ventricular remodeling after acute myocardial infarction].

OBJECTIVE: To investigate the relationship between the levels of lysophsophatidic acid (LPA) and function of left ventricular after acute myocardial infarction (AMI) and the role of LPA in ventricular remodeling and the potential mechanism. METHODS: In this study, we selected 86 patients with AMI and measured the levels of LPA and type III procollagen (PCIII) on admission and 4 day after admission, and performed echocardiographic examinations on admission and 8 approximately 10 day after admission. And according to their serum LPA value at day 4 patients were stratified into two group (group A, LPA < 6.0 micro mol/L, n = 45; group B, LPA >/= 6.0 micro mol/L, n = 41). In 40 normal individuals, level of LPA and PCIII were measured. RESULTS: (1) The patient's levels of LPA after AMI were increased (5.1 micro mol/L +/- 1.1 micro mol/L and 6.4 micro mol/L +/- 1.3 micro mol/L vs 2.5 micro mol/L +/- 1.1 micro mol/L, P = 0.0001). (2) PCIII was significantly higher in group B than that in group A (136 micro g/L +/- 10 micro g/L vs 113 micro g/L +/- 12 micro g/L, P < 0.05). Left ventricular end-diastolic diameter was significantly higher in group B than in group A (54.0 mm +/- 3.3 mm vs 51.1 mm +/- 2.7 mm, P < 0.05). (3) The elevation of LPA after AMI was closed related to the function of left ventricular (P < 0.05). CONCLUSION: The levels of LPA after AMI were increased, which may play a role in ventricular remodeling. The potential mechanism may be that LPA can stimulate cardiac myocyte hypertrophy and cardiac fibroblast proliferation and cause collagen production increasing.