Molecular Pathways in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension is a multifactorial, chronic disease process that leads to pulmonary arterial endothelial dysfunction and smooth muscular hypertrophy, resulting in impaired pliability and hemodynamics of the pulmonary vascular system, and consequent right ventricular dysfunction. Existing treatments target limited pathways with only modest improvement in disease morbidity, and little or no improvement in mortality. Ongoing research has focused on the molecular basis of pulmonary arterial hypertension and is going to be important in the discovery of new treatments and genetic pathways involved. This review focuses on the molecular pathogenesis of pulmonary arterial hypertension.     

Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease characterized by unexplained physical fatigue, cognitive and sensory dysfunction, sleeping disturbances, orthostatic intolerance, and gastrointestinal problems. People with ME/CFS often report a prodrome consistent with infections. Using regression, Bayesian and enrichment analyses, we conducted targeted and untargeted metabolomic analysis of plasma from 106 ME/CFS cases and 91 frequency-matched healthy controls. Subjects in the ME/CFS group had significantly decreased levels of plasmalogens and phospholipid ethers (p < 0.001), phosphatidylcholines (p < 0.001) and sphingomyelins (p < 0.001), and elevated levels of dicarboxylic acids (p = 0.013). Using machine learning algorithms, we were able to differentiate ME/CFS or subgroups of ME/CFS from controls with area under the receiver operating characteristic curve (AUC) values up to 0.873. Our findings provide the first metabolomic evidence of peroxisomal dysfunction, and are consistent with dysregulation of lipid remodeling and the tricarboxylic acid cycle. These findings, if validated in other cohorts, could provide new insights into the pathogenesis of ME/CFS and highlight the potential use of the plasma metabolome as a source of biomarkers for the disease.     

Systems Development Strategy: A Component Based Approach, The Architecture

An architecture for building laboratory automation systems was developed using the component-based framework. The requirements to build a flexible and adaptable automation system were exemplified through the architectural design process. Existing tools and technologies facilitated the development of this scalable architecture. Several design patterns were used to model this architecture. The influence of these patterns on systems design and the impact of Unified Modeling Language on component and interface design was explored. Integration of the system components with the peripheral components to build an automated system is discussed with emphasis on run-time configuration and component reuse.     

COVID-19 Mimics Pulmonary Dysfunction in Muscular Dystrophy as a Post-Acute Syndrome in Patients

Although progressive wasting and weakness of respiratory muscles are the prominent hallmarks of Duchenne muscular dystrophy (DMD) and long-COVID (also referred as the post-acute sequelae of COVID-19 syndrome); however, the underlying mechanism(s) leading to respiratory failure in both conditions remain unclear. We put together the latest relevant literature to further understand the plausible mechanism(s) behind diaphragm malfunctioning in COVID-19 and DMD conditions. Previously, we have shown the role of matrix metalloproteinase-9 (MMP9) in skeletal muscle fibrosis via a substantial increase in the levels of tumor necrosis factor-α (TNF-α) employing a DMD mouse model that was crossed-bred with MMP9-knockout (MMP9-KO or MMP9^-/-) strain. Interestingly, recent observations from clinical studies show a robust increase in neopterin (NPT) levels during COVID-19 which is often observed in patients having DMD. What seems to be common in both (DMD and COVID-19) is the involvement of neopterin (NPT). We know that NPT is generated by activated white blood cells (WBCs) especially the M1 macrophages in response to inducible nitric oxide synthase (iNOS), tetrahydrobiopterin (BH4), and tetrahydrofolate (FH4) pathways, i.e., folate one-carbon metabolism (FOCM) in conjunction with epigenetics underpinning as an immune surveillance protection. Studies from our laboratory, and others researching DMD and the genetically engineered humanized (hACE2) mice that were administered with the spike protein (SP) of SARS-CoV-2 revealed an increase in the levels of NPT, TNF-α, HDAC, IL-1β, CD147, and MMP9 in the lung tissue of the animals that were subsequently accompanied by fibrosis of the diaphragm depicting a decreased oscillation phenotype. Therefore, it is of interest to understand how regulatory processes such as epigenetics involvement affect DNMT, HDAC, MTHFS, and iNOS that help generate NPT in the long-COVID patients.     

Enzyme-Assisted Process for Production of Superior Quality Vanilla Extracts from Green Vanilla Pods Using Tea Leaf Enzymes

Vanilla planifolia Andrews is a perennial tropical vine and is an orchid grown for its pleasant flavor. There is an increasing trend world over for using natural flavors. Vanilla being an important food flavoring ingredient, the demand for natural vanilla extract is increasing. Hence, the aim of the present study was to prepare vanilla extract from green beans without going through the elaborate and time-consuming conventional curing process. Vanilla beans after size reduction were mixed in a suitable proportion with tea leaf enzyme extract (TLEE) and incubated to facilitate action of enzymes on vanilla flavor precursors. The beans mix was squeezed, and the filtrate was treated with ethanol to extract the vanilla flavor. TLEE-treated extracts had higher vanillin content (4.2%) compared to Viscozyme extract (2.4%). Also, it had higher intensity of vanilla flavor, sweet, and floral notes. Further, electronic nose analysis confirmed the discrimination between extracts. It was concluded that the use of TLEE is very much useful to obtain higher yield of vanilla extract and superior quality vanilla flavor, which avoids the traditional laborious and time-consuming curing process.     

Long‐term impact of nitrogen and potassium fertilizers on yield,soil nutrients and biochemical parameters of tea

A field experiment was conducted with tea cultivar UPASI‐9 over a period of 9 years to evaluate the long‐term effects of nitrogen (N) and potassium (K) fertilizers on yield, biochemical parameters, soil and leaf nutrient status. The yield increase was as high as 66% over the control for N application of 450 kg ha^?1 year^?1. Polyphenol and amino acid contents increased with increase in K application rate. Positive and significant correlation was found between nitrate reductase activity and the amino acid content of the tea shoots. While ammoniacal nitrogen in the soil was not affected by the application of fertilizer, ammonium acetate extractable K increased. The failure to apply fertilizer resulted in depletion of the organic matter status of the soil. Although increased rate of nitrogen application increased the overall yield of made tea (kg ha^?1 year^?1), the specific yield (kg kg^?1 N) declined. The soil tended to become acidic from frequent application of high doses of nitrogenous fertilizer. The leaf NK status was significantly influenced by the various treatments. Copyright © 2004 Society of Chemical Industry     

An investigation of normal and submerged condition on microstructural and tribological properties of friction stir processed AZ91-D magnesium alloy

A comparative study of micro-structural transformations and tribological properties of the friction stir processed AZ91-D magnesium (Mg) alloy in normal friction stir processing (NFSP) and submerged friction stir processing (SFSP) conditions was carried out. The optimum parameters used for processing were tool rotational speed of 1000?rpm/min, 50?mm/min of transverse speed and 6 numbers of passes. A significant reduction in grain size (28.7% and 13.1%) and increase in micro-hardness (14.55% and 8.92%) along depth and width of stir zone (SZ) of SFSPed specimen has been achieved as compared to NFSPed specimens. This change can be attributed to the dynamic recrystallisation and removal of excess frictional heat leading to inhibited post-grain growth in the processed alloy. Pin-on-disc sliding wear testing was conducted to compare the wear performance of NFSPed and SFSPed specimens. The SFSPed specimen has shown an improved wear resistance as compared to NFSPed specimens. The major prevailing wear mechanisms were abrasion, delamination, oxidation and mild plastic deformation.     

Perspective model-based visual tracking scheme for robust tracking of objects in complex environs

Multimedia Tools and Applications - Robust tracking of moving objects is still an open problem in computer vision. The problem and its difficulty depend on many factors, which includes the...     

Development of Phospholipids Vesicular Nanocarrier for Topical Delivery of Tea Tree Oil in Management of Atopic Dermatitis Using BALB/c Mice Model

This work aims to develop and evaluate the efficacy of tea tree oil (TTO) ethosomal cream with improved deposition in skin layers for treatment of atopic dermatitis (AD). Ethosomes of TTO are developed using phosphatidylcholine (2% and 3% w/v) and ethanol (20%, 30%, and 40% w/v). Ethosomes are evaluated for percent entrapment efficiency (%EE), vesicle size, zeta potential, and in vitro drug diffusion. Ethosomal creams with optimized ethosomal dispersion are developed and evaluated for physicochemical parameters, thermal stability, ex vivo permeation, skin retention, and in vitro cytotoxicity using HaCat skin cell lines in comparison to conventional creams of TTO. In vivo investigations of optimized creams are performed using BALB/c mice model. The %EE, vesicle size, and zeta potential for optimized ethosomes are found to be 76.19 ± 3.26%, 333.6 nm, and –35.3 mV, respectively. Ethosomal creams showed higher deposition in the epidermis and dermis. The optimized creams are non-cytotoxic to HaCat cell lines. The creams significantly reduce the inflammatory response by decreasing the clinical score and infiltration of white blood cells, eosinophils, and IgE antibodies. Overall efficacy of ethosomal cream is higher than conventional cream. In conclusion, optimized ethosomal cream of TTO shows good efficacy for treatment of AD. Practical applications : The method used for the formulation of ethosomes is simple and can be easily scaled up on the industrial level. The loading of TTO within ethosomes can increase the efficiency by enhanced drug deposition in the epidermis and might also improve its stability against oxidative degradation. Topical ethosomal cream of TTO can improve patient compliance by avoidance of adverse effects linked with corticosteroids and could be a possible complementary or alternative therapy in management of AD.