Skin delivery of epigallocatechin-3-gallate (EGCG) and hyaluronic acid loaded nano-transfersomes for antioxidant and anti-aging effects in UV radiation induced skin damage

The present work attempts to develop and statistically optimize transfersomes containing EGCG and hyaluronic acid to synergize the UV radiation-protective ability of both compounds, along with imparting antioxidant and anti-aging effects. Transfersomes were prepared by thin film hydration technique, using soy phosphatidylcholine and sodium cholate, combined with high-pressure homogenization. They were characterized with respect to size, polydispersity index, zeta potential, morphology, entrapment efficiency, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), in vitro antioxidant activity and ex vivo skin permeation studies. Cell viability, lipid peroxidation, intracellular ROS levels and expression of MMPs (2 and 9) were determined in human keratinocyte cell lines (HaCaT). The composition of the transfersomes was statistically optimized by Design of Experiments using Box–Behnken design with four factors at three levels. The optimized transfersome formulation showed vesicle size, polydispersity index and zeta potential of 101.2?±?6.0?nm, 0.245?±?0.069 and ?44.8?±?5.24?mV, respectively. FTIR and DSC showed no interaction between EGCG and the selected excipients. XRD results revealed no form conversion of EGCG in its transfersomal form. The optimized transfersomes were found to increase the cell viability and reduce the lipid peroxidation, intracellular ROS and expression of MMPs in HaCaT cells. The optimized transfersomal formulation of EGCG and HA exhibited considerably higher skin permeation and deposition of EGCG than that observed with plain EGCG. The results underline the potential application of the developed transfersomes in sunscreen cream/lotions for improvement of UV radiation-protection along with deriving antioxidant and anti-aging effects.     

Multi-detector computed tomography imaging of large airway pathology: A pictorial review

The tracheobronchial tree is a musculo-cartilagenous framework which acts as a conduit to aerate the lungs and consequently the entire body. A large spectrum of pathological conditions can involve the trachea and bronchial airways. These may be congenital anomalies, infections, post-intubation airway injuries, foreign body aspiration or neoplasms involving the airway. Appropriate management of airway disease requires an early and accurate diagnosis. In this pictorial essay review, we will comprehensively describe the various airway pathologies and their imaging findings by multi-detector computed tomography.     

Inhaled therapies for tuberculosis and the relevance of activation of lung macrophages by particulate drug-delivery systems

Pathogenic strains of Mycobacterium tuberculosis (Mtb) induce 'alternative activation' of lung macrophages that they colonize, in order to create conditions that promote the establishment and progression of infection. There is some evidence to indicate that such macrophages may be rescued from alternative activation by inhalable microparticles containing a variety of drugs. This review summarizes the experience of various groups of researchers, relating to observations of induction of a number of classical macrophage activation pathways. Restoration of a 'respiratory burst' and upregulation of reactive oxygen species and nitrogen intermediates through the phagocyte oxidase and nitric oxide synthetase enzyme systems; induction of proinflammatory macrophage cytokines; and finally induction of apoptosis rather than necrosis of the infected macrophage are discussed. It is suggested that there is scope to co-opt host responses in the management of tuberculosis, through the route of pulmonary drug delivery.     

Effect of omeprazole and domperidone on adult asthmatics with gastroesophageal reflux

AIM: To study the effect of combined omeprazole (Ome) and domperidone (Dom) therapy on asthma symptoms and pulmonary function in asthmatics with gastroesoph- ageal reflux. METHODS: We selected 198 asthmatics with gastroesophageal reflux diagnosed by 24-h esophageal pH monitoring to receive Ome 20 mg twice daily and Dom 10 mg three times daily or placebo for 16 wk (1:1 double-blind randomization). Spirometry was done at baseline and af- ter 16 wk of treatment. The primary outcome measures were: mean daily daytime and nighttime asthma symp- tom scores. Mean daily reflux symptom scores, albuterol use as rescue medication (number of puffs), daytime and nighttime peak expiratory flow rate (PEFR), postbroncho- dilator forced expiratory volume in 1 second (FEV1) and postbronchodilator forced vital capacity (FVC) were secondary outcome measures. RESULTS: Comparison of mean change from baseline between antireflux therapy and placebo groups revealed significant reduction in daytime asthma symptom score (17.4% vs 8.9%), nighttime asthma symptom score (19.6% vs 5.4%), reflux symptom score (8.7% vs 1.6%) and rescue medication use (23.2% vs 3.1%) after antire- flux therapy compared to mean change in placebo group (P < 0.001). There was significant improvement in morn- ing PEFR (7.9% vs 0.2%), evening PEFR (9.8% vs 0.5%), FEV1 (11.1% vs 3.78%) and FVC (9.3% vs 1.52%) in the antireflux therapy group compared to placebo on compar-ing the mean change from baseline after 16 wk (P < 0.01).     

Genetic differentiation and phylogenetic potential of Ty3/Gypsy LTR retrotransposon markers in soil and plant pathogenic fungi

Genetic diversity studies are crucial for understanding the genetic structure and evolutionary dynamics of fungal species and communities. Fungal genomes are often reshaped by their repetitive components such as transposable elements. These elements are key players in genomic rearrangements and are ideal targets for genetic diversity and evolutionary studies. Herein, we used three Ty3/Gypsy long terminal repeat retrotransposons, Grasshopper, Maggy, and Pyret, for genetic differentiation and diversity in soil and plant pathogenic fungi, representing diverse species, order, and phyla. Pyret DNA markers showed the highest gene diversity and Shannon's information indices, followed by Maggy and Grasshopper. The observed high levels of multilocus polymorphism indicate the continuous mobility of these elements after their transfer in the new host. In conclusion, this study presents novel markers for genetic differentiation and evolutionary studies of fungi, and sheds light on the prevalence of gene acquisition phenomenon in field fungi.     

Synthesis,evaluation, molecular docking,and molecular dynamics studies of novel N-(4-[pyridin-2-yloxy]benzyl)arylamine derivatives as potential antitubercular agents

A new series of novel triclosan (2,4,4′-trichloro-2′-hydroxydiphenylether) analogues were designed, synthesized, and screened for their in vitro antimycobacterial and antibacterial activities. Most of the compounds showed significant activity against Mycobacterium tuberculosis H37Rv strain with minimum inhibitory concentration (MIC) values in 20–40 μM range in GAST/Fe medium when compared with triclosan (43 μM) in the first week of assay, and after additional incubation, seven compounds, that is, 2a , 2c , 2g , 2h , 2i , 2j , and 2m , exhibited MIC values at the concentration of 20–40 μM. The compounds also showed more significant activity against Bacillus subtilis and Staphylococcus aureus. The synthesized compounds showed druggable properties, and the predicted ADME (absorption, distribution, metabolism, and excretion) properties were within the acceptable limits. The in silico studies predicted better interactions of compounds with target protein residues and a higher dock score in comparison with triclosan. Molecular dynamics simulation study of the most active compound 2i was performed in order to further explore the stability of the protein–ligand complex and the protein–ligand interaction in detail.