Cardiac pericyte reprogramming by MEK inhibition promotes arteriologenesis and angiogenesis of the ischemic heart

Pericytes (PCs) are abundant yet remain the most enigmatic and ill-defined cell population in the heart. Here, we investigated whether PCs can be reprogrammed to aid neovascularization. Primary PCs from human and mouse hearts acquired cytoskeletal proteins typical of vascular smooth muscle cells (VSMCs) upon exclusion of EGF/bFGF, which signal through ERK1/2, or upon exposure to the MEK inhibitor PD0325901. Differentiated PCs became more proangiogenic, more responsive to vasoactive agents, and insensitive to chemoattractants. RNA sequencing revealed transcripts marking the PD0325901-induced transition into proangiogenic, stationary VSMC-like cells, including the unique expression of 2 angiogenesis-related markers, aquaporin 1 (AQP1) and cellular retinoic acid–binding protein 2 (CRABP2), which were further verified at the protein level. This enabled us to trace PCs during in vivo studies. In mice, implantation of Matrigel plugs containing human PCs plus PD0325901 promoted the formation of αSMA(+) neovessels compared with PC only. Two-week oral administration of PD0325901 to mice increased the heart arteriolar density, total vascular area, arteriole coverage by PDGFRβ(+)AQP1(+)CRABP2(+) PCs, and myocardial perfusion. Short-duration PD0325901 treatment of mice after myocardial infarction enhanced the peri-infarct vascularization, reduced the scar, and improved systolic function. In conclusion, myocardial PCs have intrinsic plasticity that can be pharmacologically modulated to promote reparative vascularization of the ischemic heart

Mucin 13 expression correlates with tumor development in hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) has a poor prognosis due to ineffective therapeutic modality and lack of early diagnostic marker. Accumulating studies have shown that elevated expression of mucin 13 as potential oncogene and predictive biomarker for various cancer. However, very little is known about its expression and function for development and progression of HCC Objective: To investigate mucin 13 expression in chemically induced hepatocellular carcinoma model. Methodology: Diethyl nitrosamine (DEN) and 2-Acetylaminofluorene (2-AAF) induced method was employed for the development of hepatocellular carcinoma in Male Wistar rats. Serum and tissues were collected at regular interval of time and routinely validated for liver cancer stages. Immunohistochemistry and in situ hybridization were performed on formalin-fixed, paraffin-embedded tissues. Molecular docking studies were performed to study the interaction of mucin 13 and DEN. Results: Our results demonstrate hepatocellular adenoma as observed by histopathological analysis. Biochemical analysis showed a progressive increase in the levels of serum ALT, AST and ALP, suggesting the development and progression of hepatocellular damage. Notably, mucin 13 expression gradually elevated during consecutive stages of hepatocellular carcinoma. Interestingly, an increase in nuclear localization of mucin 13 was observed in treated group as compared to control group. In situ hybridization analysis showed that a decrease in miR-132 and miR-145, which are inversely related with mucin 13 expression. Moreover, DEN efficiently binds mucin 13 with high affinity and thus stabilize it as demonstrated by molecular docking analysis. Conclusion: These results suggest that mucin 13 expression is closely associated with hepatocarcinogenesis and could serve as a predictive candidate biomarker for HCC

Mucin 13 expression is an early indicator of hepatocellular carcinoma development

Background: Hepatocellular carcinoma (HCC) has a poor prognosis due to ineffective therapeutic modality and lack of an early marker for diagnosis. Studies show that increased mucin 13 (MUC13) expression as a possible oncogene and predictive biomarker for various cancers has been shown. But its expression and role in the development of HCC is very little known. Objective: The aim of this study is to investigate the MUC13 expression in chemically induced hepatocellular carcinoma model. Methodology: Male Wistar rats were subjected to a DEN and 2-Acetylaminofluorene (2-AAF) induced method for the development of hepatocellular carcinoma. Serum and tissues were collected at regular intervals and routinely validated for various stages of liver cancer. On formalin-fixed, paraffin-embedded tissues, immunohistochemistry and in situ hybridization were performed. The molecular interaction of mucin 13 and DEN were also performed using in silico analysis. Results: Histopathological analysis of liver tissues revealed the development of hepatocellular carcinoma with successive stages in chemically induced model HCC. Moreover, biochemical analysis showed a progressive increase in serum ALT, AST, and ALP levels, indicating the development and progression of hepatocellular damage. Notably, mucin 13 expression gradually increased during the progression of hepatocellular carcinoma. The treated group showed an increase in nuclear localization of mucin 13 as compared to the control group. In situ hybridization analysis revealed a reduction in miR-132 and miR145, both of which are inversely related to mucin 13 expression. Furthermore, molecular docking analysis showed that DEN efficiently binds mucin 13 with high affinity and thus stabilizes it. Conclusion: These findings suggest that mucin 13 expression is linked to hepatocarcinogenesis and could be used as a candidate biomarker for HCC

Semiempirical in-cylinder pressure based model for NOx prediction oriented to control applications

This work describes the development of a fast NO X predictive model oriented to engine control in diesel engines. The in-cylinder pressure is the only instantaneous input signal required, along with several mean variables that are available in the ECU during normal engine operation. The proposed model is based on the instantaneous evolution of the heat release rate and the adiabatic flame temperature (both obtained among other parameters from the in-cylinder pressure evolution). Corrections for considering the NO X reduction due to the re-burning mechanism are also included. Finally, the model is used for providing a model-based correction of tabulated values for the NO X emission at the reference conditions. The model exhibits a good behaviour when varying exhaust gas recirculation rate, boost pressure and intake temperature, while changes in the engine speed and injection settings are considered in the tabulated values. Concerning the calculation time, the model is optimised by proposing simplified sub-models to calculate the heat release and the adiabatic flame temperature. The final result is suitable for real time applications since it takes less than a cycle to complete the NO X prediction.Guardiola García, C.; López Sánchez, JJ.; Martín Díaz, J.; García Sarmiento, D. (2011). Semiempirical in-cylinder pressure based model for NOx prediction oriented to control applications. Applied Thermal Engineering. 31(16):3275-3286. doi:10.1016/j.applthermaleng.2011.05.048S32753286311

High-Sensitivity Cardiac Troponin-I Is Elevated in Patients with Rheumatoid Arthritis, Independent of Cardiovascular Risk Factors and Inflammation

We examined the hypothesis that cardiac-specific troponin-I (cTn-I), a biomarker of myocardial injury, is elevated in patients with rheumatoid arthritis (RA).RA patients have an increased incidence of heart failure (HF). Chronic myocardial injury in RA may be a mechanism for the development of HF.We compared cTn-I concentrations measured by high-sensitivity immunoassay in 164 patients with RA and 90 controls, excluding prior or active heart failure. We examined the relationship between cTn-I concentrations and cardiovascular risk factors, inflammation, and coronary artery calcium score (CACS), a measure of coronary atherosclerosis.cTn-I concentrations were 49% higher in patients with RA (median 1.15 pg/mL [IQR 0.73–1.92] than controls (0.77 pg/mL [0.49–1.28](P<0.001). The difference remained statistically significant after adjustment for demographic characteristics (P = 0.002), further adjustment for cardiovascular (CV) risk factors (P = 0.004), inflammatory markers (P = 0.008), and in a comprehensive model of CV risk factors and inflammatory markers (P = 0.03). In patients with RA, cTn-I concentrations were positively correlated with age (rho = 0.359), Framingham risk score (FRS) (rho = 0.366), and systolic blood pressure (rho = 0.248 (all P values ≤0.001)), but not with measures of inflammation or RA drug therapies. cTn-I was significantly correlated with CACS in RA in univariate analysis, but not after adjustment for age, race, sex and FRS (P = 0.79). Further model adjustments for renal function and coronary artery disease confirmed the significance of the findings.High-sensitivity cTn-I concentrations are elevated in patients with RA without heart failure, independent of cardiovascular risk profile and inflammatory markers. Elevated troponin concentrations in RA may indicate subclinical, indolent myocardial injury

Equation of Craft in India

Description ‘Equation of Craft in India’ is a design research project of Craft Future Lab, NID Ahmedabad, India under the collaborative effort of the International Centre for Indian Craft (ICIC), Dept. of Lifestyle Accessory Design (LAD), and Design for Social Innovation and Sustainability Lab (NID DESIS Lab). The project was initiated and led by Prof. Amresh Panigrahi with his fellow 16 Master level Design students of the Department of LAD batch 2018 with the prime objective of attempting to understand the current dynamics in the Indian craft sector. The origin of crafts goes a long way back, to the Indus Valley civilization. It had its fair share of evolution through the centuries that followed from the Vedic, Mauryan, Mughal periods to the British colonization and the onset of industrialization. The crafts of India have gone through several impactful events with our relatively newfound Independent democratic country and its political and economic development. The current context of craft in the 20th century takes into account the social, economic and geopolitical setting of India with the presence of various global developments in technology, import-export scenario, travel and popular mass ideas. Here the System mapping is an attempt to represent the identified components and variables and interrelationship within the current system understanding of the craft sector in India. Craft in its essence Craft is a vital source of identity for the craftsman as it derived its meaning by its local acceptance in its socio-cultural fabric. It has developed through a long line of rich cultural heritage. The function of crafts varies from being utilitarian, ornamental to finding purposes in religious, ritualistic, and festival purposes. Crafts now are much more susceptible to cross-cultural influences of the increasing spread of media, the internet, and education. The Development Commissioner of Handicrafts (DCH), India defined crafts as ‘items made by hand, often with the use of simple tools and generally artistic and traditional. They include objects of utility and objects of decoration’. The three main confluence for the creation of a craft comes with (a) an artisan along with his ability working on (b) the raw materials with a little help from the (c) simple tools that aids where human abilities limit him. The craftsmen and the craft dynamics The four significant divisions of craftsmen based on their ability are – Master-craftsmen, Craftsmen, Apprentice, and newly joined. Master-craftsmen display the highest skill and bring novelty in the craft. Apart from the newly joined category of artisans, all other craftsmen majorly learn the craft from the master craftsperson or from within the family itself, passed down through the generations. It is a labour-intensive sector where artisans get less return in terms of money, recognition, value for craft for the much more investment they put into it. The investment may be in terms of effort, time, and the number of workforces. The real success of a craft is no more confined to the ability of the craftsperson’s skills, raw material and tools. It is the time that demands the market knowledge to make the craft a success. However, the craftsman abilities are currently limited with less market knowledge and mostly restricted to the boundaries of his craft understanding. Lack of knowledge, their struggle with the craft practices and its continuity became much more complicated, which forced them to switch to other jobs or to want a different life for their children. Initiatives at organising the sector The craft & cottage industry is the most significant non-agricultural decentralized sector of the Indian economy. In the wake of the government’s attempt to organize the sector and tap into its full potential, it works on multiple value chains of the craft sector. The government provides market platforms through multiple exhibitions, Haats, fairs and emporiums, wherein efforts are put into making the customer realize the cultural context of the craft. One of the major competitors in the market remains to be the mass-produced industrialized products flooding in domestically and also via imports from other neighbouring countries. Domestically, authentic craft loses its market to mass-produced fake craft due to its comfortable, cheaper availability. Protection of crafts ingenuity The fake market affected the craftsmen and the identity of the craft which led to government initiatives aimed at creating protection and preservation of craft’s ingenuity owing to the craftsmen and its community through the creation of geographical indication (GI) tag, Craftmark logo and also through handicraft census. With over 200 crafts GI tagged, it is beneficial to the owners as they can safeguard their products from unauthorized commercial use. Presence of the GI tag has still left some room for improvements for craftsman’s awareness and fight for their rights. The Craftmark logo is an initiative to provide a mark for genuine handicraft for the consumers to authenticate their purchase. Private exhibitions and museums purposefully created for documentation and preservation of the handicrafts. Role of design in craft innovation With above systematic study, the working groups further discovered various gaps as an opportunity for design-driven strategic intervention. Practice-based Design research facilitates the application of design strategies at various levels to imagine a craft social innovation and its sustainable future

Glutaredoxin-1 Overexpression Enhances Neovascularization and Diminishes Ventricular Remodeling in Chronic Myocardial Infarction

Oxidative stress plays a critical role in the pathophysiology of cardiac failure, including the modulation of neovascularization following myocardial infarction (MI). Redox molecules thioredoxin (Trx) and glutaredoxin (Grx) superfamilies actively maintain intracellular thiol-redox homeostasis by scavenging reactive oxygen species. Among these two superfamilies, the pro-angiogenic function of Trx-1 has been reported in chronic MI model whereas similar role of Grx-1 remains uncertain. The present study attempts to establish the role of Grx-1 in neovascularization and ventricular remodeling following MI. Wild-type (WT) and Grx-1 transgenic (Grx-1Tg/+) mice were randomized into wild-type sham (WTS), Grx-1Tg/+ Sham (Grx-1Tg/+S), WTMI, Grx-1Tg/+MI. MI was induced by permanent occlusion of the LAD coronary artery. Sham groups underwent identical time-matched surgical procedures without LAD ligation. Significant increase in arteriolar density was observed 7 days (d) after surgical intervention in the Grx-1Tg/+MI group as compared to the WTMI animals. Further, improvement in myocardial functional parameters 30 d after MI was observed including decreased LVIDs, LVIDd, increased ejection fraction and, fractional shortening was also observed in the Grx-1Tg/+MI group as compared to the WTMI animals. Moreover, attenuation of oxidative stress and apoptotic cardiomyocytes was observed in the Grx-1Tg/+MI group as compared to the WTMI animals. Increased expression of p-Akt, VEGF, Ang-1, Bcl-2, survivin and DNA binding activity of NF-κB were observed in the Grx-1Tg/+MI group when compared to WTMI animals as revealed by Western blot analysis and Gel-shift analysis, respectively. These results are the first to demonstrate that Grx-1 induces angiogenesis and diminishes ventricular remodeling apparently through neovascularization mediated by Akt, VEGF, Ang-1 and NF-κB as well as Bcl-2 and survivin-mediated anti-apoptotic pathway in the infarcted myocardium