Epidemiological and Clinical Presentation of Retinoblastoma among Nepalese Children in 2019.

Suresh B.K. RasailyObjectives Retinoblastoma (RB) is rare but potentially fatal if left untreated. This study aimed to evaluate the epidemiological profile, clinical manifestation, classification, and affordability of RB treatment among Nepalese children in the year 2019. Materials and Method A multicentric, multiethnic hospital-based cross-sectional study after ethical approval from the National Health Research Council was conducted from January 2019 to December 2019 by incorporating ophthalmologists all over the nation. Twenty-seven RB centers were selected. All the RB presented in the RB centers either newly diagnosed or ongoing treatment consented to the study were included and failed to consent for the study, RB survivors were excluded from the study. Data based on demographic profile, clinical manifestation, ethnical and geographical distribution, and treatment received were collected in the customized Google Form. Each case was classified at the time of diagnosis as per the International Classification of Retinoblastoma groups and different treatment modalities offered as per grouping and staging. The affordability of treatment was calculated using a catastrophic approach. Statistical Analysis Data were entered into Microsoft Excel 2010 and analyzed using Statistical Package for Social Sciences version 20. Result A total of 34 RB cases, 21 (61.76%) in ongoing treatment group and 13 (38.2%) in newly diagnosed group presented in the RB centers. Out of total, 32 (64.7%) had unilateral and 12 (35.3%) cases had bilateral involvement. The majority of patients was from Province 1 (35.3%) and belonged to the upper caste (38.2%). Leukocoria was the most common presentation (73.9%) followed by proptosis, red eye, and phthisis bulbi. More than 75% patients presented at advanced group D (54%) and E (21%) and stage 0 (90%). More than 90% of patients received systemic chemotherapy, and 42.6% received transpupillary thermotherapy. The average cost of RB treatment was estimated to be 521% of the nonfood expense of the family which is unaffordable to almost all cases (100%). Conclusion Leukocoria is the most common mode of clinical presentation in both unilateral and bilateral RBs. Early diagnosis and appropriate treatment are key to success for saving life, sight, and eye. However, community awareness programs against RB, active referral networks, and the establishment of chemotherapy centers with trained human resources are needed to reduce loss of life, sight, and eye.

The discovery of the natural compound Boeravinone-C as a potential antiobesity drug candidate targeting pancreatic lipase using chemo-informatics-based approaches.

Obesity is a metabolic disorder distinguished by excess fat deposition in fatty tissues. Pancreatic lipase is one of the promising drug targets for treating obesity due to its critical role in the hydrolysis of triglycerides into mono-glycerides and free fatty acids. Due to unsatisfactory results and severe side effects of the current drugs available for treating obesity, there is an urgent need to identify novel therapeutic options. Boerhaavia diffusa is one of the widely known species of flowering plant commonly known as Punamava. Extracts from Punamava plants have been widely used in treating countless ailments in traditional medicine. Recently, multiple reports demonstrated the potential antiobesity activity of B. diffusa plant extracts. In this scenario, we have evaluated numerous reported B. diffusa against pancreatic lipase drug targets to identify which reported phytochemicals to have the most promising potential to act as an inhibitor for pancreatic lipase using computational approaches. All the twenty-four phytochemicals from Boerhaavia diffusa were identified as significantly strong binders with a range of binding energies between -6.0 to -8.0 Kcal/mol inside the pancreatic lipase active binding site. On the other hand, we calculated 2D Quantitative Structure-Activity Relationship (QSAR) molecular descriptor properties adhered to Lipinski's rule of five. Between twenty-four phytochemicals evaluated, Boeravinone-C, with a range binding energy of -8.0 Kcal/mol, was discovered as the best lead-like molecule, compared to marketed Orlistat, which has shown -5.6 Kcal/mol of binding energy. Conclusively, Boeravinone-C from B. diffusa extract showed promising inhibitory potential against pancreatic lipase worth further evaluation.

Cyanotriazoles are selective topoisomerase II poisons that rapidly cure trypanosome infections.

Millions who live in Latin America and sub-Saharan Africa are at risk of trypanosomatid infections, which cause Chagas disease and human African trypanosomiasis (HAT). Improved HAT treatments are available, but Chagas disease therapies rely on two nitroheterocycles, which suffer from lengthy drug regimens and safety concerns that cause frequent treatment discontinuation. We performed phenotypic screening against trypanosomes and identified a class of cyanotriazoles (CTs) with potent trypanocidal activity both in vitro and in mouse models of Chagas disease and HAT. Cryo-electron microscopy approaches confirmed that CT compounds acted through selective, irreversible inhibition of trypanosomal topoisomerase II by stabilizing double-stranded DNA:enzyme cleavage complexes. These findings suggest a potential approach toward successful therapeutics for the treatment of Chagas disease.

Basella alba stem extract integrated poly (vinyl alcohol)/chitosan composite films: A promising bio-material for wound healing.

Natural extract-based bio-composite material for wound healing is gaining much attention due to risk of infection and high cost of commercial wound dressing film causes serious problem on the human well-being. Herein, the study outlines the preparation of Poly (vinyl alcohol)/Chitosan/Basella alba stem extract (BAE) based bio-composite film through solvent casting technique and well characterized for wound healing application. Incorporation of BAE into Poly (vinyl alcohol)/Chitosan matrix has shown existence of secondary interactions confirmed by FT-IR analysis. Good morphology, thermal stability and significant improvement in flexibility (∼63.38 %) of the films were confirmed by SEM, TGA and Mechanical test results, respectively. Hydrophilic property (∼9.04 %), water vapor transmission rate (∼70.07 %), swelling ability (∼14.7 %) and degradation rate (∼14.04 %) were enhanced with increase in BAE content. In-vitro studies have shown good antibacterial activity against foremost infectious bacterial strains S. aureus and E. coli. Additionally, BAE integrated Poly (vinyl alcohol)/Chitosan film has amplified anti-inflammatory (∼79.38 %) property, hemocompatibility and excellent biocompatibility (94.9 %) was displayed by cytotoxicity results. Moreover, in-vitro scratch assay and cell adhesion test results illustrated prominent wound healing (96.5 %) and adhesion. Overall results of the present work proclaim that developed bio-composite film could be utilized as a biomaterial in wound care applications.

Efficacy and safety of polyherbal formulation as an add-on to standard-of-care in mild-to-moderate COVID-19: A randomized, double-blind, placebo-controlled trial.

Background: Novel corona virus disease-2019 (COVID-19) pandemic is a significant contributor to morbidity and mortality in affected individuals. Modulating the immune response in COVID-19 is now an established treatment approach. Polyherbal formulations have long been assessed for their potential immune modulating effects and are expected to be beneficial on COVID-19. Methods: This study aims at assessing the efficacy and safety of polyherbal formulation (referred as IP) in comparison to placebo, as add on to the standard of care (SOC), in patients with mild to moderate COVID-19 patients. Hospitalized RT-PCR positive patients were randomized to either SOC + IP or SOC + Placebo arm. The viral load (VL) was assessed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Immunological parameters were also assessed. The clinical improvement was assessed using a numeric rating scale (NRS) and WHO ordinal scale, and follow-up period was 30 days. Results: Seventy-two patients were randomized to SOC + IP (n = 39) and SOC + Placebo (n = 33) arms. There was significant reduction in VL in SOC + IP arm from day 0-4 (p = 0.002), compared to SOC + Placebo arm (p = 0.106). Change in the NRS score and WHO score was significant in both arms, however, the difference between the two arms was statistically significant in favour of IP arm. The increase in Th1 response was significant in SOC + IP arm (p = 0.023), but not in SOC + Placebo arm. COVID-19 specific antibodies were numerically higher in the SOC + IP arm. Conclusion: The study finds that polyherbal formulation significantly reduces VL and contributes to immunomodulation and improvement in clinical conditions without side effects.

Performance of Swarnadhara breeder hens supplemented with reduced levels of different copper forms.

BACKGROUND AND AIM: Copper (Cu) is a vital mineral involved in various physiological and biochemical processes, growth, and productivity of animals and birds. Birds can absorb only a small fraction of Cu and most is excreted, contaminating soil and aquatic environment which is toxic for microorganisms, plants, animals, and humans. This study evaluated the possibility of use of organic and nanoparticles sources of Cu to reduce supplementation level without compromising the performance of breeder hens. MATERIALS AND METHODS: A total of 224 Swarnadhara breeder hens were divided into seven treatment groups having four replicates in each. The basal diet (control) containing 20 ppm inorganic Cu (100% of standard recommendation) and six test diets containing 20, 15, and 10 ppm (100, 75, and 50% of standard recommendation) from Cu organic source, and 15, 10, and 5 ppm (75, 50, and 25%) from Cu nanoparticles (Cu-NP), were prepared and offered to respective treatment groups for a duration of 20 weeks. RESULTS: The hen day egg production, hen housed egg production, feed conversion ratio egg mass, albumen index, yolk index, total fat content, and color score were not affected by the source and inclusion level of Cu. The feed intake was significantly (p<0.05) lower at 15 ppm and egg weight was significantly (p<0.05) higher at 10 ppm Cu-NP supplemental level, but was non-significant in other treatment groups compared to control. The body weight gain was significantly (p<0.05) higher at 20 ppm organic and 15 ppm Cu-NP inclusion. The egg shape index and Haugh unit were significantly (p<0.05) lower at 10 and 15 ppm of Cu-NP inclusion level, respectively. The shell thickness was improved (p<0.05) at 20 and 15 ppm organic and 15 and 10 ppm Cu-NP inclusion level. The egg fertility rate was shown to be significantly (p<0.05) higher at 20 ppm organic Cu inclusion group, but the hatchability based on total number of eggs set improved (p<0.05) at 20 and 15 ppm organic Cu inclusion level while all treatment groups were comparable to control. The hatchability of fertilized egg and chick's quality significantly (p<0.05) improved, while embryonic and chick mortality after hatching before-sorting was significantly (p<0.05) reduced at 15 ppm of Cu-NP inclusion group. CONCLUSION: It was concluded that the inorganic Cu can be replaced with 50% of organic or 25% of nanoparticles form of Cu without jeopardizing the breeder hens' productivity, egg quality characteristics, hatchability, and progeny.

Effect of Pepper-Containing Diets on the Diversity and Composition of Gut Microbiome of Drosophila melanogaster.

One of the greatest impacts on the gastrointestinal microbiome is diet because the host and microbiome share the same food source. In addition, the effect of diet can diverge depending on the host genotype. Diets supplemented with phytochemicals found in peppers might cause shifts in the microbiome. Thus, understanding how these interactions occur can reveal potential health implications associated with such changes. This study aims to explore the gut microbiome of different Drosophila genetic backgrounds and the effects of dietary pepper treatments on its composition and structure. We analyzed the gut microbiomes of three Drosophila melanogaster genetic backgrounds (Canton-S, Oregon-RC, and Berlin-K) reared on control and pepper-containing diets (bell, serrano, and habanero peppers). Results of 16S rRNA gene sequencing revealed that the variability of Drosophila gut microbiome can be driven mainly by genetic factors. When the abundance of these communities is considered, pepper-containing diets also appear to have an effect. The most relevant change in microbial composition was the increment of Lactobacillaceae and Acetobacteraceae abundance in the pepper-containing diets in comparison with the controls in Oregon-RC and Berlin-K. Regression analysis demonstrated that this enhancement was associated with the content of phenolic compounds and carotenoids of the peppers utilized in this study; specifically, to the concentration of ß-carotene, ß-cryptoxanthin, myricetin, quercetin, and apigenin.

Safety and efficacy of an herbal formulation in patients with renal calculi - A 28 week, randomized, double-blind, placebo-controlled, parallel group study.

BACKGROUND: Urolithiasis is a growing problem worldwide. Many a times, asymptomatic stones are kept under observation. Many herbal preparations are available for the same, but they lack proper scientific documentation. OBJECTIVE: To study the anti-urolithiatic effect of an herbal preparation, Subap Plus (IP) capsules in patients with asymptomatic renal calculi of size ranging from 4 to 9 mm. MATERIAL AND METHODS: This was a prospective, randomized, double-blind, placebo-controlled clinical trial conducted in a tertiary care hospital in Pune, India. Patients with asymptomatic renal calculi of 4-9 mm size were randomized (1:1, block randomization) to one of the group Subap Plus (treatment group) or placebo (placebo group). The study outcome included change in visual analog scale (VAS), change in the surface area and density of calculi and their expulsion. Statistical analysis was performed using student's t-test and Chi-square test. RESULTS: A total of 120 patients were screened and 84 were enrolled who met the eligibility criteria, of which 65 patients completed the trial (treatment, n = 34; placebo, n = 31). The VAS score significantly decreased in the treatment group (6.9-1.8) than placebo group (7.2-6.8) (p < 0.001). The surface area and density were decreased by 47.58% (p < 0.008) and 43.01% (p < 0.001), respectively, in the treatment group than the placebo group. The expulsion of calculi was significantly higher in the treatment group than placebo group (20.59 vs. 3.23%, p < 0.03). CONCLUSION: Patients treated with herbal formulation showed better expulsion rate and reduction in surface area and density than the placebo group.

Discovery of Potent Inhibitors of 11ß-Hydroxysteroid Dehydrogenase Type 1 Using a Novel Growth-Based Protocol of in Silico Screening and Optimization in CONTOUR.

With the continuous progress in ultralarge virtual libraries which are readily accessible, it is of great interest to explore this large chemical space for hit identification and lead optimization using reliable structure-based approaches. In this work, a novel growth-based screening protocol has been designed and implemented in the structure-based design platform CONTOUR. The protocol was used to screen the ZINC database in silico and optimize hits to discover 11ß-HSD1 inhibitors. In contrast to molecular docking, the virtual screening process makes significant improvements in computational efficiency without losing chemical equities through partitioning 1.8 million ZINC compounds into fragments, docking fragments to form key hydrogen bonds with anchor residues, reorganizing molecules into molecular fragment trees using matched fragments and common substructures, and then regrowing molecules with the help of developed intelligent growth features inside the protein binding site to find hits. The growth-base screening approach is validated by the high hit rate. A total of 50 compounds have been selected for testing; of these, 15 hits having diverse scaffolds are found to inhibit 11ß-HSD1 with IC50 values of less than 1 µM in a biochemical enzyme assay. The best hit which exhibits an enzyme IC50 of 33 nM is further developed to a novel series of bicyclic 11ß-HSD1 inhibitors with the best inhibition of enzyme IC50 of 3.1 nM. The final lead candidate exhibits IC50 values of 7.2 and 21 nM in enzyme and adipocyte assays, respectively, displayed greater than 1000-fold of selectivity over 11ß-HSD2 and two other related hydroxysteroid dehydrogenases, and can serve as good starting points for further optimization to develop clinical candidates.

Discovery of BI 135585, an in vivo efficacious oxazinanone-based 11ß hydroxysteroid dehydrogenase type 1 inhibitor.

A potent, in vivo efficacious 11ß hydroxysteroid dehydrogenase type 1 (11ß HSD1) inhibitor (11j) has been identified. Compound 11j inhibited 11ß HSD1 activity in human adipocytes with an IC50 of 4.3nM and in primary human adipose tissue with an IC80 of 53nM. Oral administration of 11j to cynomolgus monkey inhibited 11ß HSD1 activity in adipose tissue. Compound 11j exhibited >1000× selectivity over other hydroxysteroid dehydrogenases, displays desirable pharmacodynamic properties and entered human clinical trials in 2011.

In vitro studies on medicinal plants used against bacterial diabetic foot ulcer (BDFU) and urinary tract infected (UTI) causing pathogens.

The pus samples from diabetic foot ulcer patients and urine samples from urinary tract infected patients were collected and inoculated in nutrient agar plates. The colonies showing different morphologies were streaked on selective agar plates. The antibacterial assay of selected commercial antibiotics was tested against the foot ulcer and urinary tract isolates. The result revealed that most of the organisms were found to be resistant against the antibiotics. Screening of antibacterial activity of selected plants, methanol extracts of plants were prepared and tested against foot ulcer pathogens. Among the plants used, the methanolic extract Tragia involucrata was very effective against the foot ulcer pathogens and to separate the compounds present in the methanolic extract of T. involucrata, when it was subjected to column chromatography. The fractions obtained were further checked for their antibacterial property and fraction 1 which inhibited the pathogens, were subjected to thin layer chromatography and the structure of the particular phytochemical compound was elucidated by NMR study. The spices were tested for their antibacterial property against the urinary tract pathogens. Among the spices tested; Allium sativum inhibited the growth of the pathogens isolated from urinary tract infection. It can be concluded that the plants extract can be used to discover natural products that may serve as lead for the development of new pharmaceuticals addressing the major therapeutic needs.

Cinnamon Converts Poor Learning Mice to Good Learners: Implications for Memory Improvement.

This study underlines the importance of cinnamon, a commonly used natural spice and flavoring material, and its metabolite sodium benzoate (NaB) in converting poor learning mice to good learning ones. NaB, but not sodium formate, was found to upregulate plasticity-related molecules, stimulate NMDA- and AMPA-sensitive calcium influx and increase of spine density in cultured hippocampal neurons. NaB induced the activation of CREB in hippocampal neurons via protein kinase A (PKA), which was responsible for the upregulation of plasticity-related molecules. Finally, spatial memory consolidation-induced activation of CREB and expression of different plasticity-related molecules were less in the hippocampus of poor learning mice as compared to good learning ones. However, oral treatment of cinnamon and NaB increased spatial memory consolidation-induced activation of CREB and expression of plasticity-related molecules in the hippocampus of poor-learning mice and converted poor learners into good learners. These results describe a novel property of cinnamon in switching poor learners to good learners via stimulating hippocampal plasticity.

The effect of audio therapy to treat postoperative pain in children undergoing major surgery: a randomized controlled trial.

PURPOSE: To evaluate the analgesic effect of music and audiobooks in children undergoing major surgical procedures when compared to a control (silence) group. METHODS: The study was a prospective and randomized trial. Children undergoing major surgeries were randomized to one of the three groups: music, audiobook or control (silence). The primary outcome was the pain burden reduction by two treatments within 48 h postoperatively. Pain burden was measured using the area under the pain scale versus the 30 min interval for each treatment. RESULTS: 60 patients were recruited and 56 completed the study. Pain burden was reduced in the music and audiobook groups compared to control, median (IQR) of -60 (-90 to 0), -45 (-90 to 0) and 0 (-30 to 90) (min × pain score), respectively, P = 0.04. A linear regression analysis demonstrated an independent group effect on pain reduction even after adjusting for the mean pain scores recorded at the beginning of the treatment, slope of regression line -56.8 ± 24 goodness of fit r (2) = 0.25 and slope significantly different from 0 (P = 0.02). CONCLUSIONS: Audio therapy is an efficacious adjunct method to decrease post-surgical pain in children undergoing major surgeries. Audio therapy should be considered as an important strategy to minimize pain in children undergoing major surgery.

Evaluation of antihyperlipidemic potency of a polyherbomineral formulation (AF-LIP) in experimental animal models.

There is a growing interest in the screening of antihyperlipidemic activity and the present study deals with the screening of a polyherbomineral formulation (AF-LIP) which possess many important ingredients reported to have antihyperlipidemic potency. Acute antihyperlipidemic activity was evaluated by using Triton WR-1339 (100 mg kg(-1)) and chronic, induced by high fat diet. Total Cholesterol (TC), triglycerides (TG), Low Density Lipoproteins (LDL), High Density Lipoproteins (HDL) and Very Low Density Lipoproteins (VLDL) were examined in addition to HMG-CoA reductase enzyme activity and fecal cholesterol excretion. In Triton WR-1339 (acute model) at the dose of 400 mg kg(-1), AF-LIP significantly lowered TC, TG, very Low Density Lipoproteins Cholesterol (VLDL-C), Low Density Lipoproteins Cholesterol (LDL-C) levels with simultaneous increase in High Density Lipoproteins Cholesterol (HDL-C) levels (p < 0.01) at 6 and 24 h. Also there was significant reduction in TC and LDL-C levels at 48 h at the dose of 400 mg kg(-1). In chronic model also at the dose of 100, 200 and 400 mg kg(-1), AF-LIP significantly reduced (p < 0.001) TC and LDL-C levels with increase in HDL-C levels. TG and VLDL-C levels were also not much affected. HMG-CoA reductase enzyme activity when estimated was not much decreased. Also AF-LIP showed significant reduction in atherogenic index (p < 0.01) with significant increase in HDL/TC ratio (p < 0.01). Fecal cholesterol excretion was significantly enhanced (p < 0.01) in all the test doses of AF-LIP. AF-LIP may be beneficial for the treatment of atherosclerosis, since atherosclerosis is one of the secondary complications of hyperlipidemia.

Indolcarboxamide is a preclinical candidate for treating multidrug-resistant tuberculosis.

New chemotherapeutic compounds against multidrug-resistant Mycobacterium tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis (TB). We have identified and characterized the indolcarboxamides as a new class of antitubercular bactericidal agent. Genetic and lipid profiling studies identified the likely molecular target of indolcarboxamides as MmpL3, a transporter of trehalose monomycolate that is essential for mycobacterial cell wall biosynthesis. Two lead candidates, NITD-304 and NITD-349, showed potent activity against both drug-sensitive and multidrug-resistant clinical isolates of Mtb. Promising pharmacokinetic profiles of both compounds after oral dosing in several species enabled further evaluation for efficacy and safety. NITD-304 and NITD-349 were efficacious in treating both acute and chronic Mtb infections in mouse efficacy models. Furthermore, dosing of NITD-304 and NITD-349 for 2 weeks in exploratory rat toxicology studies revealed a promising safety margin. Finally, neither compound inhibited the activity of major cytochrome P-450 enzymes or the hERG (human ether-a-go-go related gene) channel. These results suggest that NITD-304 and NITD-349 should undergo further development as a potential treatment for multidrug-resistant TB.

Evaluation of a multi-herb supplement for erectile dysfunction: a randomized double-blind, placebo-controlled study.

BACKGROUND: Evidence is lacking for multi-ingredient herbal supplements claiming therapeutic effect in sexual dysfunction in men. We examined the safety and efficacy of VigRX Plus (VXP) - a proprietary polyherbal preparation for improving male sexual function, in a double blind, randomized placebo-controlled, parallel groups, multi-centre study. METHODS: 78 men aged 25-50 years of age; suffering from mild to moderate erectile dysfunction (ED), participated in this study. Subjects were randomized to receive VXP or placebo at a dose of two capsules twice daily for 12 weeks. The international index of erectile function (IIEF) was the primary outcome measure of efficacy. Other efficacy measures were: Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), Serum testosterone, Semen analysis, Investigator's Global assessment and Subjects' opinion. RESULTS: In subjects receiving VXP, the IIEF-Erectile Function (EF) scores improved significantly as compared to placebo. After 12 weeks of treatment, the mean (sd) IIEF-EF score at baseline increased from 16.08 (2.87) to 25.08 (4.56) in the VXP group versus 15.86 (3.24) to 16.47 (4.25) in the placebo group (P < 0.0001). Similar results were observed in each of the remaining four domains of the IIEF (orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction).There was a significant difference for VXP versus placebo comparison of mean (sd) EDITS scores of patients: 82.31(20.23) vs 36.78(22.53) and partners :(82.75(9.8) vs 18.50(9.44);P < 0.001. Thirty-five out of 39 (90%) subjects from the VXP group and one (3%) from the placebo group wished to continue with the treatment they received. Investigator's global assessment rated VXP therapy as very good to excellent in more than 50% patients and placebo therapy as fair to good in about 25% of patients. Incidence of side effects and subject's rating for tolerability of treatment was similar in both groups. CONCLUSIONS: VigRX Plus was well tolerated and more effective than placebo in improving sexual function in men. TRIAL REGISTRATION: Clinical Trial Registry India, CTRI/2009/091/000099, 31-03-2009.

Metastasis-associated protein 1/histone deacetylase 4-nucleosome remodeling and deacetylase complex regulates phosphatase and tensin homolog gene expression and function.

Metastasis-associated protein 1 (MTA1) is widely overexpressed in human cancers and is associated with malignant phenotypic changes contributing to morbidity in the associated diseases. Here we discovered for the first time that MTA1, a master chromatin modifier, transcriptionally represses the expression of phosphatase and tensin homolog (PTEN), a tumor suppressor gene, by recruiting class II histone deacetylase 4 (HDAC4) along with the transcription factor Yin-Yang 1 (YY1) onto the PTEN promoter. We also found evidence of an inverse correlation between the expression levels of MTA1 and PTEN in physiologically relevant breast cancer microarray datasets. We found that MTA1 up-regulation leads to a decreased expression of PTEN protein and stimulation of PI3K as well as phosphorylation of its signaling targets. Accordingly, selective down-regulation of MTA1 in breast cancer cells increases PTEN expression and inhibits stimulation of the PI3K/AKT signaling. Collectively, these findings provide a mechanistic role for MTA1 in transcriptional repression of PTEN, leading to modulation of the resulting signaling pathways.

Structure-activity relationships of antitubercular nitroimidazoles. 3. Exploration of the linker and lipophilic tail of ((s)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-yl)-(4-trifluoromethoxybenzyl)amine (6-amino PA-824).

The (S)-2-nitro-6-(4-(trifluoromethoxy)benzyloxy)-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine named PA-824 (1) has demonstrated antitubercular activity in vitro and in animal models and is currently in clinical trials. We synthesized derivatives at three positions of the 4-(trifluoromethoxy)benzylamino tail, and these were tested for whole-cell activity against both replicating and nonreplicating Mycobacterium tuberculosis (Mtb). In addition, we determined their kinetic parameters as substrates of the deazaflavin-dependent nitroreductase (Ddn) from Mtb that reductively activates these pro-drugs. These studies yielded multiple compounds with 40 nM aerobic whole cell activity and 1.6 µM anaerobic whole cell activity: 10-fold improvements over both characteristics from the parent molecule. Some of these compounds exhibited enhanced solubility with acceptable stability to microsomal and in vivo metabolism. Analysis of the conformational preferences of these analogues using quantum chemistry suggests a preference for a pseudoequatorial orientation of the linker and lipophilic tail.

Lipid lowering activity of ethanolic extract of leaves of Aegle marmelos (Linn.) in hyperlipidaemic models of Wistar albino rats.

Lipid lowering effect of 50% ethanolic extract of the leaves of A. marmelos (Linn.) was evaluated in triton and diet induced hyperlipidaemic models of Wistar albino rats. The extract at 125 and 250 mg/kg dose levels inhibited the elevation in serum cholesterol and triglycerides levels on Triton WR 1339 administration in rats. The extract at the same dose levels significantly attenuated the elevated serum total cholesterol and triglycerides with an increase in the high-density lipoprotein cholesterol in high-fat diet- induced hyperlipidaemic rats. The standard drugs atorvastatin in the former and gemfibrozil in the latter studies showed slightly better effects.

Invitro antioxidant activity of selected antiasthmatic herbal constituents.

Asthmatic patients are more subjected to continuous oxidative stress. Roosting the antioxidant defenses of asthma patient could be beneficial as it may help thwart symptoms of the lung disease and asthma. Considering these facts different plant extracts and phytoconstituents with proven anti asthmatic property had been subjected to antioxidant study at various combinations using Diphenyl Vicryl Hydrazyl radical scavenging method, Hydrogen Peroxide radical scavenging method, Nitric oxide radical inhibition method, ABTS radical scavenging method and Lipid peroxidation assay method.All the selected herbal based constituents and extracts at different combination showed a potent antioxidant activiy by Nitric oxide radical inhibition activiy method followed by ABTS method. The present finding suggests that the selected plant based anti asthmatic constituents namely Coleus extract (10% Forskolin), Piper longum extract (20% Piperine), CurcuminC3Complex (60% Curcumin), Vasaka (30% Vasicinone), Forskolin (95%), Pperine (98%), Curcumin C3 Complex (98.5%) and Vasicinone (75%) could be utilised in alternate anti asthmatic therapy, since they play a vital role in scavenging Nitric oxide which could prevent the bronchial inflammation in asthmatic patients.