Indoxyl sulfate aggravates podocyte damage through the TGF-ß1/Smad/ROS signaling pathway.

INTRODUCTION: Hyperglycaemia induces the production of a large quantity of reactive oxygen species (ROS) and activates the transforming growth factor ß1(TGF-ß1)/Smad signalling pathway, which is the main initiating factor in the formation of diabetic nephropathy. Indoxyl sulfate (IS) is a protein-binding gut-derived uraemic toxin that localizes to podocytes, induces oxidative stress and inflames podocytes. The involvement of podocyte damage in diabetic nephropathy through the TGF-ß1/) signalling pathway is still unclear. METHODS: In this study, we cultured differentiated rat podocytes in vitro and measured the expression levels of nephrin, synaptopodin, CD2AP, SRGAP2a and α-SMA by quantitative real-time PCR (qRT‒PCR) and western blotting after siRNA-mediated TGF-ß1 silencing, TGF-ß1 overexpression and the presence of the ROS inhibitor acetylcysteine. We detected the expression levels of nephrin, synaptopodin, CD2AP, SRGAP2a, SRGAP2a in the Smad2/3, phosphorylated-Smad2/3 (p-Smad2/3), Smad7, NADPH oxidase 4 (NOX4), and ROS levels under high glucose (HG) and IS conditions. RESULTS: The results indicated that nephrin, synaptopodin, CD2AP and SRGAP2a expressions were significantly upregulated and α-SMA expression was significantly downregulated in the presence of HG under siRNA-mediated TGF-ß1 silencing or after the addition of acetylcysteine. However, in the presence of HG, the expressions of nephrin, synaptopodin, CD2AP and SRGAP2a were significantly downregulated, and the expression of α-SMA was significantly upregulated with the overexpression of TGF-ß1. IS supplementation under HG conditions further significantly reduced the expressions of nephrin, synaptopodin, CD2AP and SRGAP2a; altered the expressions of Smad2/3, p-Smad2/3, Smad7 and NOX4; and increased ROS production in podocytes. CONCLUSIONS: This study suggests that IS may modulate the expression of nephrin, synaptopodin, CD2AP and SRGAP2a by regulating the ROS and TGF-ß1/Smad signalling pathways, providing new theoretical support for the treatment of diabetic nephropathy.

Critical role of water conditions in the responses of autumn phenology of marsh wetlands to climate change on the Tibetan Plateau.

The Tibetan Plateau, housing 20% of China's wetlands, plays a vital role in the regional carbon cycle. Examining the phenological dynamics of wetland vegetation in response to climate change is crucial for understanding its impact on the ecosystem. Despite this importance, the specific effects of climate change on wetland vegetation phenology in this region remain uncertain. In this study, we investigated the influence of climate change on the end of the growing season (EOS) of marsh wetland vegetation across the Tibetan Plateau, utilizing satellite-derived Normalized Difference Vegetation Index (NDVI) data and observational climate data. We observed that the regionally averaged EOS of marsh vegetation across the Tibetan Plateau was significantly (p < .05) delayed by 4.10 days/decade from 2001 to 2020. Warming preseason temperatures were found to be the primary driver behind the delay in the EOS of marsh vegetation, whereas preseason cumulative precipitation showed no significant impact. Interestingly, the responses of EOS to climate change varied spatially across the plateau, indicating a regulatory role for hydrological conditions in marsh phenology. In the humid and cold central regions, preseason daytime warming significantly delayed the EOS. However, areas with lower soil moisture exhibited a weaker or reversed delay effect, suggesting complex interplays between temperature, soil moisture, and EOS. Notably, in the arid southwestern regions of the plateau, increased preseason rainfall directly delayed the EOS, while higher daytime temperatures advanced it. Our results emphasize the critical role of hydrological conditions, specifically soil moisture, in shaping marsh EOS responses in different regions. Our findings underscore the need to incorporate hydrological factors into terrestrial ecosystem models, particularly in cold and dry regions, for accurate predictions of marsh vegetation phenological responses to climate change. This understanding is vital for informed conservation and management strategies in the face of current and future climate challenges.

Numerical modeling of the effects of the shape and aspect ratio of 3D curved fiber on the percolation threshold and electrical conductivity of conductive polymer composites.

For designing conductive polymer composites (CPCs), understanding how the fiber curvature affects the percolation behavior of curved conductive fibers is essential for determining the effective electrical conductivity σeff of the CPCs. In this work, CPCs were considered as a polymer matrix filled with the random packing of overlapped curved spherocylinders. The geometries of the curved spherocylinders were defined, and inter-curved spherocylinder contact-detecting and system-spanning fiber cluster searching algorithms were developed. The finite-size-scaling method was used to explore how the aspect ratio α and bending central angle θ of a curved spherocylinder affect the percolation threshold ϕc of an overlapped curved spherocylinder system in 3D space. The findings suggest that ϕc decreases as α increases and increases initially before declining as θ increases. An empirical approximation formula was proposed to quantify the effect of the curved spherocylinder's morphology, characterized by the dimensionless excluded volume Vdex of the curved spherocylinder, on ϕc. The new rigorous bound for ϕc of the soft-curved spherocylinder system was further proposed. A random resistor network model was constructed, and the reliability of this model was validated by comparing the simulations and published data. Finally, a fitting formula was developed to assess the impacts of the normalized reduced density (η - ηc)/ηc and Vdex on the σeff of CPCs. A distinct linear correlation between σeff and (η - ηc)/ηc was constructed, denoted as σeff ∼ [(η - ηc)/ηc]t(α,θ). An empirical approximation model was proposed to establish the relationship between the fiber shape and conductivity exponent t. Our study may provide a theoretical hint for the design of CPCs.

Assessment of urinary podocalyxin as an alternative marker for urinary albumin creatinine ratio in early stage of diabetic kidney disease in older patients.

This study's objective is to evaluate the correlation relationship between Podocalyxin (PCX), an urinary marker of podocytes, urinary albumin-creatinine ratio (ACR) and the predictive value of PCX in the routine screen of early diabetic kidney disease (DKD) among older people. We also aimed to explore its prediction value despite of other metabolic factor and how PCX alters in the predictive power for early stage of diabetic nephropathy. In retrospective, 320 cases of older patients diagnosed with type 2 diabetes mellitus who met both inclusion and exclusion criteria were collected and divided with levels of urinary albumin, that is, normal albuminuria group, microalbuminuria group and healthy group. The correlation coefficient between PCX and ACR, and the odds ratio of PCX were gauged in the study. Area under the receiver operating characteristic (ROC) curve was also calculated. There were 188 patients in the normal group with urine ACR<30mg/g, and 132 patients in the microproteinuria group with urine ACR 30-300mg/g. 132 cases of DKD diagnosed with ACR, among them, 104 cases of DKD were predicted by PCX. The percentage correction value was 78.8%. The following parameters such as gender, age, course of disease, glycated hemoglobin, triglyceride, total cholesterol, BMI, blood pressure, uric acid, and eGFR were used as variables for adjustment to establish the prediction model of urine PCX and ACR. Multiple logistic regression test was carried out to evaluate against the predictive ability of the model. The area under the ROC curve corresponding to the regression model after adjustment is 0.952. Although factors such as the course of disease, HbA1C, UA, and eGFR could influence on the predictive ability of PCX, PCX still has a good ability to predict early DKD in older patients. Therefore, it could be used as a diagnostic indicator for early-stage DKD in older patients.

Assessment of urinary podocalyxin as an alternative marker for urinary albumin creatinine ratio in early stage of diabetic kidney disease in older patients / Evaluación de la podocalyxina urinaria como marcador alternativo del cociente de creatinina albúmina urinaria en la etapa inicial de la enfermedad renal diabética en pacientes mayores

This study's objective is to evaluate the correlation relationship between Podocalyxin (PCX), an urinary marker of podocytes, urinary albumin-creatinine ratio (ACR) and the predictive value of PCX in the routine screen of early diabetic kidney disease (DKD) among older people. We also aimed to explore its prediction value despite of other metabolic factor and how PCX alters in the predictive power for early stage of diabetic nephropathy. In retrospective, 320 cases of older patients diagnosed with type 2 diabetes mellitus who met both inclusion and exclusion criteria were collected and divided with levels of urinary albumin, that is, normal albuminuria group, microalbuminuria group and healthy group. The correlation coefficient between PCX and ACR, and the odds ratio of PCX were gauged in the study. Area under the receiver operating characteristic (ROC) curve was also calculated. There were 188 patients in the normal group with urine ACR<30mg/g, and 132 patients in the microproteinuria group with urine ACR 30–300mg/g. 132 cases of DKD diagnosed with ACR, among them, 104 cases of DKD were predicted by PCX. The percentage correction value was 78.8%. The following parameters such as gender, age, course of disease, glycated hemoglobin, triglyceride, total cholesterol, BMI, blood pressure, uric acid, and eGFR were used as variables for adjustment to establish the prediction model of urine PCX and ACR. Multiple logistic regression test was carried out to evaluate against the predictive ability of the model. The area under the ROC curve corresponding to the regression model after adjustment is 0.952. Although factors such as the course of disease, HbA1C, UA, and eGFR could influence on the predictive ability of PCX, PCX still has a good ability to predict early DKD in older patients. (AU)

El objetivo de este estudio es evaluar la relación de correlación entre la podocalyxina (PCX), un marcador urinario de podocitos, el cociente albúmina-creatinina urinaria (ACR) y el valor predictivo de PCX en el cribado rutinario de la enfermedad renal diabética temprana (ERC) en personas mayores.. También nos propusimos explorar su valor de predicción a pesar de otros factores metabólicos y cómo la PCX altera el poder predictivo de la nefropatía diabética en la etapa temprana. En retrospectiva, se recogieron 320 casos de pacientes mayores diagnosticados con diabetes mellitus tipo 2 que cumplían con los criterios de inclusión y exclusión y se dividieron con los niveles de albúmina urinaria, es decir, grupo de albuminuria normal, grupo de microalbuminuria y grupo sano. El coeficiente de correlación entre PCX y ACR, y la razón de posibilidades de PCX se midió en el estudio. También se calculó el área bajo la curva de característica operativa del receptor (ROC). Hubo 188 pacientes en el grupo normal con ACR en orina <30 mg /gy 132 pacientes en el grupo de microproteinuria con ACR en orina 30-300 mg /g. 132 casos de DKD diagnosticados con ACR, entre ellos 104 casos de DKD fueron predichos por PCX. El valor de corrección porcentual fue del 78,8%. Los siguientes parámetros como sexo, edad, curso de la enfermedad, hemoglobina glucosilada, triglicéridos, colesterol total, IMC, presión arterial, ácido úrico y TFGe se utilizaron como variables de ajuste para establecer el modelo de predicción de PCX y ACR en orina. Se realizó una prueba de regresión logística múltiple para evaluar la capacidad predictiva del modelo. El área bajo la curva ROC correspondiente al modelo de regresión después del ajuste es 0,952. Aunque factores como el curso de la enfermedad, HbA1C, UA y eGFR podrían influir en la capacidad predictiva de PCX, PCX todavía tiene una buena capacidad para predecir la DKD temprana en pacientes mayores. (AU)

A Universal Method for Modeling and Characterizing Non-Circular Packing Systems Based on n-Point Correlation Functions.

A universal method for modeling and characterizing non-circular particles is developed. The n-point correlation functions (n = 1, 2 and 3) are efficiently computed with a GPU parallel computing procedure. An algorithm for dynamic packing of impenetrable non-circular particles is developed based on the fast estimation of overlap information using a one-point correlation function. The packing algorithm is independent of particle shape and proved to be reliable by examples of polygons and super-ellipses. In addition, penetrable packings are generated in an efficient and precise way. Using a two-point correlation function, these non-circular packs are accurately characterized and compared in terms of features such as penetrable and impenetrable, packing fraction and particle shape. In addition, three-point correlation functions are also illustrated and discussed.

Third-Order Effective Properties for Random-Packing Systems Using Statistical Micromechanics Based on a GPU Parallel Algorithm in Fast Computing n-Point Correlation Functions.

Estimating the effective properties of a particulate system is the most direct way to understand its macroscopic performance. In this work, we accurately evaluate the third-order approximations involving the three-point microstructural parameter ζ, which can be calculated from a triple integral involving 1-, 2-, and 3-point correlation functions. A GPU-based parallel algorithm was developed for quickly computing the n-point correlation functions, and the results agree well with analytical solutions. The effective thermal conductivity and diffusion coefficient are calculated by the third-order approximates for the random-packing systems of a super-ellipsoid. By changing the parameters of the super-ellipsoid, the particle-shape effect can be predicted for both the thermal conductivity and diffusion coefficient.

Adaptive method for estimating information from a polarized skylight.

The acquisition and processing of skylight polarization information forms the cornerstone in modern navigation systems that are developed by imitating certain biological mechanisms. The accuracy of skylight polarization mode information plays a major part in improving the accuracy of polarized light navigation. This paper mainly focuses on developing a methodology that can avoid the error caused by the inaccurate rotation of the polarizer and manual readings from non-electrical equipment, when the time-sequence polarization measurement system is used to obtain the skylight polarization mode information. We propose an adaptive algorithm that can obtain the pictures of angle of polarization and degree of polarization with sets of random rotation angles with no need for precise readings for the rotation angle of the polarizer. By allocating initial random values to rotation angles, a simple iterative estimation method like the Gaussian-Newton method can be used to converge calculated angle of polarization and degree of polarization values to their respective real values. The experiment results show that the proposed method can be used to estimate polarization information with high accuracy and universality under various experiment settings including both sunny and cloudy weathers. Meanwhile, the time efficiency of the proposed method is comparable to traditional methods.

Error Types of and Strategies on Learning Chinese Connectives: A Study on Chinese as a Second Language Learners' Writing.

The correct use of connectives has great influence on language learners' writing proficiency, while errors of connectives are common in foreign learners' interlanguages. This study examines the types of errors that occur in native English-speaking learners' Chinese writing, the possible causes for the errors, and the learners' consequent learning strategies. The present research adopted corpora investigation, questionnaire survey, and focus-group interviews to examine the error types, causes of identified errors, and related learning strategies. Data analysis indicated that: (1) the main error types made by native English-speaking learners from high to low are misuse, overuse, mismatch, misplacement, and underuse of connectives; (2) causes related to intralingual transfer greatly contributes to the presence of errors; and (3) memory, social, and cognitive strategies were the most preferred, followed by metacognitive and compensation strategies, and then by effective strategies which were the least preferred. These findings showed that different strategies can be employed to cope with different errors in writing. The study further suggests that teachers and educators need to help native English-speaking learners find strategies that work best for them in terms of learning Chinese connectives.

Controversies in the application of corticosteroids for pediatric septic shock treatment: a preferred reporting items for systematic reviews and meta-analysis-compliant updated meta-analysis.

OBJECTIVES: Septic shock is the major cause of childhood mortality. However, the application of corticosteroids remains controversial. This work aimed to analyze the source of controversy based on existing data and recent randomized controlled trials by meta-analysis and to assess whether it can avoid these factors to guide clinical treatment. METHODS: We searched the public databases up to 8 June 2019 and included only randomized controlled trials. The primary outcome was mortality. Sensitivity analysis, subgroup analysis, and dose-response meta-analysis were performed in this work. RESULTS: We included twelve studies consisting of 701 children in the meta-analysis. For primary outcome, the fixed-effect model showed steroids could significantly reduce the mortality compared to the control (Odds Ratio: 0.67; 95% confidence interval: 0.46-0.98; P = .041). However, the random-effect model showed a negative result (Odds Ratio: 0.69; 95% confidence interval: 0.32-1.51; P = .252). None of the subgroup results rejected the null hypothesis that the overall effect equaled zero. Dose-response effect analysis showed that increased dosage at a low dosage might reduce the mortality, while at a high dosage, increasing the dose might increase the mortality. Moreover, the grading of recommendations assessment, development, and evaluation level of evidence is low for mortality. CONCLUSIONS: Corticosteroid application is not recommended for septic shock children under current medical conditions.

lncRNA Oip5-as1 attenuates myocardial ischaemia/reperfusion injury by sponging miR-29a to activate the SIRT1/AMPK/PGC1α pathway.

OBJECTIVES: Myocardial ischaemia/reperfusion (MI/R) injury is associated with adverse cardiovascular outcomes after acute myocardial infarction. However, the molecular mechanisms underlying MI/R injury are unclear. This study investigated the role of long non-coding RNA (lncRNA) Oip5-as1 in regulating mitochondria-mediated apoptosis during MI/R injury. MATERIALS AND METHODS: Sprague-Dawley rats were subjected to MI/R induced by ligation of the left anterior descending coronary artery followed by reperfusion. H9c2 cells were incubated under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions to mimic in vivo MI/R. RT-qPCR and Western blot were used to evaluate gene and protein levels. CCK-8 assay, biochemical assay and flow cytometric analysis were performed to assess the function of Oip5-as1. The dual-luciferase gene reporter assay and RIP assay were conducted as needed. RESULTS: Oip5-as1 expression was downregulated in the hearts of rats with MI/R and in H9c2 cells treated with OGD/R. Oip5-as1 overexpression alleviated reactive oxygen species-driven mitochondrial injury and consequently decreased apoptosis in MI/R rats and H9c2 cells exposed to OGD/R. Mechanistically, Oip5-as1 acted as a competing endogenous RNA of miR-29a and thus decreased its expression. Inhibition of miR-29a reduced the oxidative stress and cytotoxicity induced by OGD/R. Overexpression of miR-29a reversed the anti-apoptotic effect of Oip5-as1 in H9c2 cells treated with OGD/R. Further experiments identified SIRT1 as a downstream target of miR-29a. Oip5-as1 upregulated SIRT1 expression and activated the AMPK/PGC1α pathway by targeting miR-29a, thus reducing the apoptosis triggered by OGD/R. However, these effects were reversed by a selective SIRT1 inhibitor, EX527. CONCLUSIONS: Oip5-as1 suppresses miR-29a leading to activation of the SIRT1/AMPK/PGC1α pathway, which attenuates mitochondria-mediated apoptosis during MI/R injury. Our findings thus provide new insights into the molecular mechanisms of MI/R injury.

Breakfast prevalence of medical students is higher than students from nonmedical faculties in Inner Mongolia Medical University.

BACKGROUND: Skipping breakfast is becoming common worldwide. Our previous studies showed that the breakfast prevalence was relatively low. METHODS: In three cross-sectional studies, breakfast prevalence in various populations in Inner Mongolia Medical University campus in 2011, 2013 and 2017 was investigated. Risk of skipping breakfast in 2017 was analyzed. In follow-up study, the incidence, RR, AR% and PAR% of eating and skipping breakfast from 2011 to 2013 were calculated. RESULTS: Data of 18,231 individuals were collected. Breakfast prevalence growth was 16.1% during the seven years. The annulus growth of breakfast prevalence was 9.3% (2013 vs 2011, P < 0.001) and 6.3% (2017 vs 2013, P < 0.001). The breakfast prevalence of three cross-sectional studies (73.0 vs 64.9%, P < 0.001; 79.5 vs 69.6%, P < 0.001; and 82.8 vs 77.4%, P < 0.001) and the breakfast incidence of a two-year follow-up study (70.6 vs 48.5% 95% CI: 1.12-1.90) both showed that breakfast consumption in medical students is higher than that in students from nonmedical faculties. The seven-year average breakfast prevalence of male and female medical students (70.0 and 82.5%) was 1.31 (95% CI: 1.23-1.39) and 1.09 (95% CI: 1.06-1.11) that of male and female students from nonmedical faculties (53.6 and 75.8%), respectively. CONCLUSION: Medical students have a higher breakfast consumption than nonmedical students. Male students from nonmedical faculties have the lowest breakfast prevalence and the highest breakfast skip risk in our university.

Improved Models of Imaging of Skylight Polarization Through a Fisheye Lens.

Researchers have found that some animals can use the skylight polarization pattern for navigation. It is also expected to use the skylight polarization pattern for human navigating in the near future. However, the challenge is that the need for a more accurate and efficient model of the imaging of skylight polarization is always felt. In this paper, three improved models of imaging of skylight polarization are proposed. The proposed models utilize the analysis of the distribution of the skylight polarization pattern after the polarization imaging system. Given that the skylight polarization pattern after the polarization imaging system is distorted, the focus of this paper is on the degree of distortion of the skylight polarization pattern in these imaging models. Experiments in clear weather conditions demonstrate that the proposed model operates close to the actual acquired skylight polarization pattern.

Multi-scale assessment of eco-hydrological resilience to drought in China over the last three decades.

Understanding to what extent can terrestrial ecosystems maintain their structure and functions and recover after being hit by drought is critical for sustainable ecosystem management and drought mitigation practices. This study assesses multi-scale (i.e., at grid, climate type, land use, basin, province scales) eco-hydrological resilience to drought over China during the period of 1982-2015, based on Standard Evapotranspiration Deficit Index as well as satellite-retrieved evapotranspiration (ET) and net primary production (NPP). Over the last three decades, the ecosystem water use efficiency (eWUE) increased in most regions of China (especially in Northeast China and North China Plain) in the context of climate change. The western China showed a significant wetting trend with ascending ET, GPP and eWUE. The SEDI and ET showed significantly increasing tendencies but the ecosystem GPP and eWUE did not exhibit obvious responses to regional wetting in the middle and lower reaches of Yangtze River basin. Most terrestrial ecosystems in China were found overall resilient to drought except for mild temperature-fully humid-warm summer at the climate type scale, water type at the land use scale, Northwest Rivers at the basin scale as well as Ningxia, Qinghai, Shanghai and Hong Kong at the province scale. These findings would facilitate the identification of most drought-vulnerable regions for ecosystem management and taking reasonable adaptation measures (e.g., use of alternative water resources or reuse water, water conservation and smart irrigation) to ensure the sustainability of terrestrial ecosystems during the drought periods over China.

Biomimetic chitosan-graft-polypeptides for improved adhesion in tissue and metal.

Inspired by the mussel foot protein and chitosan-based macromolecular adhesives, a series of chitosan-graft-polypeptides were synthesized by ring-opening polymerization of three N-carboxyanhydrides (NCAs) - 3,4-dihydroxyphenylalanine-N-carboxyanhydride (DOPA-NCA), cysteine-NCA (Cys-NCA) and arginine-NCA (Arg-NCA) - using partial-NH2-protected chitosan as an initiator. These copolymers demonstrated good biodegradability and low cytotoxicity. The results of lap-shear adhesion test showed that the maximum lap-shear adhesion strength on the porcine skin and aluminum sheet were 195.97 ± 21.1 kPa and 3080 ± 320 kPa, respectively, and the maximum tensile adhesion strength on bone was 642.70 ± 61.1 kPa. The rat experiment in vivo showed that these copolymers exhibited good hemostatic performance and can promote the healing of skin wound and bone fracture. It is expected that thesecopolymeric adhesives will have broad applications in hemostasis and soft tissue adhesions.

Impacts of Chinese Grain for Green program and climate change on vegetation in the Loess Plateau during 1982-2015.

Remote sensing based vegetation index provides a practical method for the monitoring of vegetation dynamics at regional and global scales. Here, using a long-term remotely sensed normalized difference vegetation index (NDVI) dataset, we quantified the vegetation changes in the Loess Plateau (LP) over the last three decades (1982-2015), which includes the period before the Chinese"Grain for Green Program"(GGP) was launched (1982-1999), and the period after the GGP (1999-2015). The correlations between the NDVI and four climate related variables, i.e., precipitation, temperature, root-soil moisture (RSM), and a drought proxy-standardized evapotranspiration deficit index (SEDI), were also examined. The results indicated that, (i) the GGP strongly changed the vegetation in the LP. The growing-season mean NDVI (GSM-NDVI) and the annual mean NDVI (AM-NDVI) decreased slightly before the GGP launched in 1999, with slopes of -3.38×10-3 and-8.00×10-4year-1, respectively. However, they showed slight and significant (p<0.05) increases after the GGP, with slopes of 4.75×10-3 and 2.32×10-3year-1, respectively. (ii) Climate change (i.e., warming and drying) resulted in adverse effects on vegetation in the LP during the period before the GGP. However, the observed changes (i.e., wetting and reduced drought) exerted positive effects on the vegetation during the period after the GGP. (iii) Inter-annual variations of spatially averaged NDVI over the LP were primarily determined by RSM rather than any other climate related variables. In the southeastern LP, the inter-annual variation of GSM-NDVI was mainly determined by precipitation and SEDI, while the inter-annual variation of AM-NDVI was mainly caused by SEDI and RSM. Inter-annual variations of both GSM-NDVI and AM-NDVI were mainly determined by SEDI and RSM in the northwestern LP, and by temperature in the southwestern LP.

Norcantharidin combined with diamminedichloroplatinum inhibits tumor growth and cancerometastasis of hepatic carcinoma in murine.

AIM: Norcantharidin (NCTD) has been used as a clinical antineoplastic drug in China for several years, and diamminedichloroplatinum is a valuable clinical cancer chemotherapy agent. Here, we tried to investigate the effects of NCTD plus diamminedichloroplatinum on hepatic carcinoma in murine. MATERIALS AND METHODS: In vivo and in vitro investigations on anticancer effects of the two drugs were individually made. RESULT: In vitro, the combination of the two drugs resulted in apparent apoptosis and cell proliferation inhibitions of H22 cancer cells. Meanwhile, their coadministration in vivo produced significant suppressions of tumor growth and cancerometastasis. Further, CD31 immunohistochemistry and matrigel tube formation assay demonstrated that angiogenesis was inhibited by NCTD plus diamminedichloroplatinum in vivo and in vitro, respectively. CONCLUSION: Based on the findings, we concluded that NCTD plus diamminedichloroplatinum may have an additive anticancer efficacy because the two drugs work in different ways, and thus, their combination had inhibited cancer cell proliferations and tumor angiogenesis more effectively than either of the compounds alone.

Network pharmacology-based identification of major component of Angelica sinensis and its action mechanism for the treatment of acute myocardial infarction.

Background: To decipher the mechanisms of Angelica sinensis for the treatment of acute myocardial infarction (AMI) using network pharmacology analysis. Methods: Databases were searched for the information on constituents, targets, and diseases. Cytoscape software was used to construct the constituent-target-disease network and screen the major targets, which were annotated with the DAVID (Database for Annotation, Visualization and Integrated Discovery) tool. The cardioprotective effects of Angelica sinensis polysaccharide (ASP), a major component of A. sinensis, were validated both in H9c2 cells subjected to simulated ischemia by oxygen and glucose deprivation and in rats with AMI by ligation of the left anterior coronary artery. Results: We identified 228 major targets against AMI injury for A. sinensis, which regulated multiple pathways and hit multiple targets involved in several biological processes. ASP significantly decreased endoplasmic reticulum (ER) stress-induced cell death both in vitro and in vivo In ischemia injury rats, ASP treatment reduced infarct size and preserved heart function. ASP enhanced activating transcription factor 6 (ATF6) activity, which improved ER-protein folding capacity. ASP activated the expression of p-AMP-activated protein kinase (p-AMPK) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α). Additionally, ASP attenuated levels of proinflammatory cytokines and maintained a balance in the oxidant/antioxidant levels after AMI. Conclusion:In silico analysis revealed the associations between A. sinensis and AMI through multiple targets and several key signaling pathways. Experimental data indicate that ASP protects the heart against ischemic injury by activating ATF6 to ameliorate the detrimental ER stress. ASP's effects could be mediated via the activation of AMPK-PGC1α pathway.