Evaluating the novel parameters for assessing the LAA function and thrombus formation with nonvalvular atrial fibrillation.

The dysfunction of left atrial appendage (LAA) is prone to form thrombus when atrial fibrillation (AF) sustained more than 48 h. Traditional 2D-TEE (transesophageal echocardiography) can not accurate evaluate the function of LAA. The purpose of this study is to analyze the relationship of LAA function parameters and thrombus formation in patients with non-valvular atrial fibrillation (NVAF) by real-time three-dimensional transesophageal echocardiography (RT-3D-TEE). High risk patients can be identified according to the characteristics of ultrasonic index in patients with left atrial appendage thrombosis, which has important clinical value and significance in the risk assessment, guiding treatment and judging prognosis. We examined the relationship between the echocardiographic parameters of LAA function and the incidence of thrombus in 102 NVAF patients. They underwent RT-3D-TEE and left atrial appendage thrombus (LAAT)/severe spontaneous echocardiographic contrast (SSEC) was found in 67 patients (thrombus group) but absent in the remaining 35 patients (non-thrombus group). After measured by QLAB software, the LAA functional parameters were significantly associated with LAAT/SEC formation. Univariate analysis indicated that AF time, LAD, LVEF, LAA-OAmax, LAAVmax, LAAVI and LAAEF demonstrated a positive association (P < 0.05). However, logistic regression analysis identified that AF time (OR:1.73, P < 0.05)、LAAEF (OR:4.09, P < 0.01)and LAAVI (OR:3.28, P < 0.01) were independent predictors of LAAT/SSEC. In patients with nonvalvular atrial fibrillation, echocardiographic parameters of LAA function are significantly associated with LAAT/SSEC.

Identification of novel bioactive molecules from garlic bulbs: A special effort to determine the anticancer potential against lung cancer with targeted drugs.

Garlic (Allium sativum L.), is a predominant spice, which is used as an herbal medicine and flavoring agent, since ancient times. It has a rich source of various secondary metabolites such as flavonoids, terpenoids and alkaloids, which have various pharmacological properties. Garlic is used in the treatment of various ailments such as cancer, diabetes and cardiovascular diseases. The present study aims to explore the plausible mechanisms of the selected phytocompounds as potential inhibitors against the known drug targets of non-small-cell lung cancer (NSCLC). The phytocompounds of garlic were identified by gas chromatography-mass spectrometry (GC-MS) technique. Subsequently, the identified phytocompounds were subjected to molecular docking to predict the binding with the drug targets, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) and group IIa secretory phospholipase A2 (sPLA2-IIA). Molecular dynamics is used to predict the stability of the identified phytocompounds against NSCLC drug targets by refining the intermolecular interactions formed between them. Among the 12 phytocompounds of garlic, three compounds[1,4-dimethyl-7-(1-methylethyl)-2-azulenyl]phenylmethanone, 2,4-bis(1-phenylethyl)-phenol and 4,5-2 h-oxazole-5-one,4-[3,5-di-t-butyl-4-methoxyphenyl] methylene-2-phenyl were identified as potential inhibitors, which might be suitable for targeting the different clinical forms of EGFR and dual inhibition of the studied drug targets to combat NSCLC. The result of this study suggest that these identified phytocompounds from garlic would serve as promising leads for the development of lead molecules to design new multi-targeting drugs to address the different clinical forms of NSCLC.

In-vitro phytochemical and pharmacological bio-efficacy studies on Azadirachta indica A. Juss and Melia azedarach Linn for anticancer activity.

In this study, phyto-constituents, anti-bacterial and anticancer activity of Azadirachta indica A. Juss and Melia azedarach Linn was analyzed. High Performance Liquid Chromatography (HPLC) and Thin Layer Chromatography (TLC) fingerprint profile of methanol extract of A. indica and M. azedarach was carried out. The present findings showed the presence of phytochemicals such as, steroids, alkaloids, phenols, flavonoids, saponins, tannins, anthraquinone and aminoacids in A. indica and M. azedarach extracts. HPLC profiling of methanolic extract of A. indica and M. azaderach revealed eleven and ten fractions of compounds were visualized in the form of peak. In TLC methanolic extract of A. indica was separated by eight distinct phenolic and three steroidal bands and M. azaderach showed sixteen distinct phenolic and three different steroidal bands. In antibacterial activity, Among the various extracts 50 µg/ml methanolic extracts of A. indica showed high activity against K. pneumoniae (14 mm) and M. azedarach showed high activity against S. aureus (15 mm). The results suggest that the crude methanolic extracts of A. indica and M. azedarach possess significant phytochemical properties compared to other extracts and hence the phytochemicals of M. azedarach and A. indica can be exploited for plant based anticancer and antimicrobial agents in the near future.

Acetaminophen Induced Hepatotoxicity in Wistar Rats--A Proteomic Approach.

Understanding the mechanism of chemical toxicity, which is essential for cross-species and dose extrapolations, is a major challenge for toxicologists. Standard mechanistic studies in animals for examining the toxic and pathological changes associated with the chemical exposure have often been limited to the single end point or pathways. Toxicoproteomics represents a potential aid to the toxicologist to understand the multiple pathways involved in the mechanism of toxicity and also determine the biomarkers that are possible to predictive the toxicological response. We performed an acute toxicity study in Wistar rats with the prototype liver toxin; the acetaminophen (APAP) effects on protein profiles in the liver and its correlation with the plasma biochemical markers for liver injury were analyzed. Three separate groups--control, nontoxic (150 mg/kg) and toxic dose (1500 mg/kg) of APAP--were studied. The proteins extracted from the liver were separated by 2-DE and analyzed by MALDI-TOF. The differential proteins in the gels were analyzed by BIORAD's PDQuest software and identified by feeding the peptide mass fingerprint data to various public domain programs like Mascot and MS-Fit. The identified proteins in toxicity-induced rats were classified based on their putative protein functions, which are oxidative stress (31%), immunity (14%), neurological related (12%) and transporter proteins (2%), whereas in non-toxic dose-induced rats they were oxidative stress (9%), immunity (6%), neurological (14%) and transporter proteins (9%). It is evident that the percentages of oxidative stress and immunity-related proteins were up-regulated in toxicity-induced rats as compared with nontoxic and control rats. Some of the liver drug metabolizing and detoxifying enzymes were depleted under toxic conditions compared with non-toxic rats. Several other proteins were identified as a first step in developing an in-house rodent liver toxicoproteomics database.