PEGylated liposome containing sildenafil for the treatment of hypertension

The purpose of this study was to prepare PEGylated liposomes containing sildenafil for the treatment of pulmonary arterial hypertension. PEGylated liposomes were prepared by thin film hydration method by varying the concentration of lipids. The prepared liposomes were characterized for the particle size, PDI, zeta potential, % entrapment efficiency and in-vitro release study. The optimized formulation exhibits a particle size of 104.27±1.4 nm, PDI of 0.449±0.02, zeta potential of -42.9±0.7 along with the maximum encapsulation of drug i.e. 87.30±2.6. Optimized formulation showed % cumulative drug release of 85.38±0.26 in 48 hr.  From the study it can be concluded that the PEGylated liposomes containing sildenafil for the treatment of pulmonary arterial hypertension provides a sustained release of drug and further studies are required to confirm their efficacy at clinical level. Keywords: Sildenafil; PEGylated liposomes; Pulmonary arterial hypertension; % entrapment efficienc

Calpain activity is negatively regulated by a KCTD7-Cullin-3 complex via non-degradative ubiquitination

Calpains are a class of non-lysosomal cysteine proteases that exert their regulatory functions via limited proteolysis of their substrates. Similar to the lysosomal and proteasomal systems, calpain dysregulation is implicated in the pathogenesis of neurodegenerative disease and cancer. Despite intensive efforts placed on the identification of mechanisms that regulate calpains, however, calpain protein modifications that regulate calpain activity are incompletely understood. Here we show that calpains are regulated by KCTD7, a cytosolic protein of previously uncharacterized function whose pathogenic mutations result in epilepsy, progressive ataxia, and severe neurocognitive deterioration. We show that KCTD7 works in complex with Cullin-3 and Rbx1 to execute atypical, non-degradative ubiquitination of calpains at specific sites (K398 of calpain 1, and K280 and K674 of calpain 2). Experiments based on single-lysine mutants of ubiquitin determined that KCTD7 mediates ubiquitination of calpain 1 via K6-, K27-, K29-, and K63-linked chains, whereas it uses K6-mediated ubiquitination to modify calpain 2. Loss of KCTD7-mediated ubiquitination of calpains led to calpain hyperactivation, aberrant cleavage of downstream targets, and caspase-3 activation. CRISPR/Cas9-mediated knockout of Kctd7 in mice phenotypically recapitulated human KCTD7 deficiency and resulted in calpain hyperactivation, behavioral impairments, and neurodegeneration. These phenotypes were largely prevented by pharmacological inhibition of calpains, thus demonstrating a major role of calpain dysregulation in KCTD7-associated disease. Finally, we determined that Cullin-3-KCTD7 mediates ubiquitination of all ubiquitous calpains. These results unveil a novel mechanism and potential target to restrain calpain activity in human disease and shed light on the molecular pathogenesis of KCTD7-associated disease

Community acquired pneumonia with shock, severe hypoxemia and leucopenia: Is the etiology methicillin resistant Staphylococci?

A young, male presented to the emergency department with respiratory signs and symptoms along with shock and leucopenia. The suspected diagnosis of methicillin resistant Staphylococcus aureus (MRSA) necrotizing pneumonia was confirmed later radiographically and microbiologically. This entity is common in childhood, but rarely reported in adults. This form of pneumonia affects young individuals without any comorbid illness. This is the first reported case of necrotizing pneumonia caused by community acquired-MRSA from Indian subcontinent. The probability to predict etiology of pneumonia from clinical signs is low; yet in the presence of shock, severe hypoxemia and leucopenia suspicion of MRSA should be kept high and hence that prompt initiation of appropriate antimicrobials may reduce mortality

LT-FS-ID: Log-Transformed Feature Learning and Feature-Scaling-Based Machine Learning Algorithms to Predict the <i>k</i>-Barriers for Intrusion Detection Using Wireless Sensor Network

The dramatic increase in the computational facilities integrated with the explainable machine learning algorithms allows us to do fast intrusion detection and prevention at border areas using Wireless Sensor Networks (WSNs). This study proposed a novel approach to accurately predict the number of barriers required for fast intrusion detection and prevention. To do so, we extracted four features through Monte Carlo simulation: area of the Region of Interest (RoI), sensing range of the sensors, transmission range of the sensor, and the number of sensors. We evaluated feature importance and feature sensitivity to measure the relevancy and riskiness of the selected features. We applied log transformation and feature scaling on the feature set and trained the tuned Support Vector Regression (SVR) model (i.e., LT-FS-SVR model). We found that the model accurately predicts the number of barriers with a correlation coefficient (R) = 0.98, Root Mean Square Error (RMSE) = 6.47, and bias = 12.35. For a fair evaluation, we compared the performance of the proposed approach with the benchmark algorithms, namely, Gaussian Process Regression (GPR), Generalised Regression Neural Network (GRNN), Artificial Neural Network (ANN), and Random Forest (RF). We found that the proposed model outperforms all the benchmark algorithms

<b style="">Evaluation of antifungal activity of <i>Salvadora</i><i> persica</i> Linn.</b><b style=""> leaves</b>

372-374Invasive fungal infections are significant causes of morbidity and mortality, particularly in immuno-compromised patients. In vitro antifungal activity of dried leaf extract of Salvadora persica Linn. was assessed against Aspergillus niger, A. flavus, A. xylinium and Candida albicans by zone of inhibition method using Clotrimazole as a positive control. The leaf extract was found active against all three species of Aspergillus but the extract did not show significant activity against C. albicans