bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis, characterization and in-vitro antitubercular activity of isoniazid-gelatin conjugate
Authors: Cassano Roberta , Trombino Sonia , Ferrarelli Teresa , Cavalcanti Paolina , Giraldi Cristina , Lai Francesco , Loy Giuseppe , Picci Nevio 
Published: February 2012

Abstract

Objectives
A novel and simple method to synthesize antitubercular-protein conjugate by solid phase synthesis was developed employing a carboxypolystyrene resin. The aim was to covalently bind a drug with antitubercular activity, isoniazid, to a biomacromolecule, gelatin, widely used in the pharmaceutical, cosmetic and food industry.

Methods
Calorimetric and 1H NMR analyses were performed to verify the bond formation between the antitubercular drug and gelatin. After absorption isoniazid delivers toxic metabolites and so an oxidation test with tert-butyl hydroperoxide was performed to assess the amount of toxic metabolites released from the prodrug (gelatin linked to isoniazid), compared with isoniazid itself.

Key findings
Spectrophotometric analysis revealed that the protein derivative was an excellent isoniazid prodrug since there was a 40% reduction in release of toxic metabolites (isonicotinic acid) by the prodrug. The results clearly showed that antitubercular moieties, covalently linked to a natural polymer, allowed the introduction of peculiar features for specific pharmaceutical applications into the macromolecule. In addition, antitubercular activity of the new polymer was determined by Middlebrook 7H11 medium against Mycobacterium tuberculosis complex.

Conclusions
The new isoniazid-gelatin conjugate showed significant antitubercular activity and for this reason should be useful as an efficacious tool in the treatment of tuberculosis.
Novel actions of progesterone: what we know today and what will be the scenario in the future?
Authors: Kaore Shilpa N , Langade Deepak Kumar , Yadav Vijay Kumar , Sharma Parag , Thawani Vijay R , Sharma Raj 
Published: February 2012

Abstract

Objectives
This article is aimed to review the novel actions of progesterone, which otherwise is considered as a female reproductive hormone. The article focuses on its important physiological actions in males too and gives an overview of its novel perspectives in disorders of central and peripheral nervous system.

Key findings
Progesterone may have a potential benefit in treatment of traumatic brain injury, various neurological disorders and male related diseases like benign prostatic hypertrophy (BPH), prostate cancer and osteoporosis. Norethisterone (NETA), a progesterone derivative, decreases bone mineral loss in male castrated mice suggesting its role in osteoporosis. In the future, progesterone may find use as a male contraceptive too, but still needs confirmatory trials for safety, tolerability and acceptability. Megestrol acetate, a progesterone derivative is preferred in prostatic cancer. Further, it may find utility in nicotine addiction, traumatic brain injury (recently entered Phase III trial) and Alzheimer's disease, diabetic neuropathy and crush injuries. Studies also suggest role of progesterone in stroke, for which further clinical trials are needed. The non genomic actions of progesterone may be in part responsible for these novel actions.

Summary
Although progesterone has shown promising role in various non-hormonal benefits, further clinical studies are needed to prove its usefulness in conditions like stroke, traumatic brain injury, neuropathy and crush injury. In male related illnesses like BPH and prostatic Ca, it may prove a boon in near future. New era of hormonal male contraception may be initiated by use of progesterone along with testosterone.
Tyrosine-like condensed derivatives as tyrosinase inhibitors
Authors: Matos Maria João , Santana Lourdes , Uriarte Eugenio , Serra Silvia , Corda Marcella , Fadda Maria Benedetta , Era Benedetta , Fais Antonella 
Published: February 2012

Abstract

Objectives
We report the pharmacological evaluation of a new series of 3-aminocoumarins differently substituted with hydroxyl groups, which have been synthesized because they include in their structures the tyrosine fragment (tyrosine-like compounds), with the aim of discovering structural features necessary for tyrosinase inhibitory activity.

Methods
The synthesized compounds 4 and 7–9 were evaluated in vitro as mushroom tyrosinase inhibitors.

Key findings
Two of the described compounds showed lower IC50 (concentration giving 50% inhibition of tyrosinase activity) than umbelliferone, used as a reference compound.

Conclusions
Compound 7 (IC50 = 53 µm) was the best tyrosinase inhibitor of this small series, having an IC50 value 10-fold lower than umbelliferone. Compound 7 (3-amino-7-hydroxycoumarin) had amino and hydroxyl groups precisely mimicking the same positions that both groups occupy on the tyrosine molecule.
Condensational growth of combination drug-excipient submicrometer particles for targeted high-efficiency pulmonary delivery: evaluation of formulation and delivery device
Authors: Hindle Michael , Longest P Worth 
Published: February 2012

Abstract

Objectives
The objective of this study was to investigate the in-vitro particle-size growth of combination drug and excipient submicrometer aerosols generated from a series of formulations and two aerosol delivery devices.

Methods
Submicrometer combination drug and excipient particles were generated experimentally using both the capillary aerosol generator and the Respimat inhaler. Budesonide and albuterol sulfate were used as model drugs and were formulated with sodium chloride, citric acid and mannitol as excipients in various ratios. Aerosol growth was evaluated in-vitro in a coiled-tube geometry designed to provide residence times and thermodynamic conditions consistent with the airways.

Key findings
Submicrometer combination drug : excipient aerosols when exposed to simulated respiratory conditions increased to micrometer size suitable for pulmonary deposition. It was possible to control the aerosol growth ratio by altering: (1) the hygroscopic excipient, (2) the drug : excipient ratio and (3) the drug. The applicability of this approach was demonstrated using the capillary aerosol generator and the Respimat inhaler.

Conclusions
The enhanced excipient growth approach may enable the delivery of submicrometer aerosol particles that increase in size within the airways and result in high percentages of pulmonary deposition.
Hepatoprotective activity of Feronia limonia root
Authors: Jain Mahendra , Kapadia Rakhee , Jadeja Ravirajsinh N , Thounaojam Menaka C , Devkar Ranjitsinh V , Mishra Shri H 
Published: February 2012

Abstract

Objectives
The aim of this study was to evaluate the hepatoprotective potential of a methanolic extract and of marmesin isolated from the root bark of Feronia limonia.

Methods
Activity levels of aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT), cell viability and cell death were evaluated in HepG2 cells (human liver hepatoma cells) treated with CCl4 in the presence or absence of F. limonia extract or marmesin. Plasma activity levels of AST, ALT, bilirubin, alkaline phosphatase, protein, hepatic antioxidants, lipid peroxidation and histopathological evaluations were carried out in rats treated with CCl4 alone or co-supplemented with F. limonia extract or marmesin in a dose-dependent manner.

Key findings
In-vitro co-supplementation of F. limonia methanolic extract or marmesin significantly minimized alteration in levels of AST and ALT and improved cell viability. Oral administration of F. limonia methanolic extract or marmesin significantly prevented CCl4-induced elevation in the plasma markers of hepatic damage and hepatic lipid peroxidation and a decrease in hepatic antioxidants. In-vivo hepatoprotective potential of F. limonia methanolic extract and marmesin was evident from the minimal alterations in the histoarchitecture of liver.

Conclusions
This has been the first scientific report on the hepatoprotective potential of F. limonia root bark methanolic extract and marmesin.
Physical activity does not attenuate the obesity risk of TV viewing in youth
Authors: Rey‐López J. P. , Ruiz J. R. , Vicente‐Rodríguez G. , Gracia‐Marco L. , Manios Y. , Sjöström M. , De Bourdeaudhuij I. , Moreno L. A. ,   HELENA Study Group
Published: February 2012

SummaryObjectiveThis study aimed to examine the association of television (TV) time, the frequency of meals while watching TV and the presence of TV set in the bedroom with total and abdominal obesity and to assess whether physical activity (PA) attenuates the obesity risk of TV viewing.MethodsCross‐sectional data were obtained from 2200 adolescents (46% boys) from 10 European cities, The Healthy Lifestyle in Europe by Nutrition in Adolescence study, between 2006 and 2007. TV viewing, PA (by accelerometry) and body composition were measured. Binary logistic regression analyses were performed.ResultsEven adjusting by vigorous PA, TV in the bedroom (odds ratio [OR]: 1.33, 95% confidence interval [CI], 1.01–1.74) and >4 h d−1 TV during week days (OR: 1.30, 95% CI, 1.02–1.67) (in boys) and eating every day with TV (OR: 1.18, 95% CI, 1.07–1.30) and >2 h d−1 TV during weekend days (OR: 1.68, 95% CI, 1.25–2.26) (in girls) were significantly associated with total obesity. Likewise, in both sexes, having a TV set at bedroom was significantly associated with abdominal obesity.ConclusionsAdolescents spending excessive TV time are prone to obesity independently of their PA levels. Families should put TV sets out of adolescents’ bedroom and keep TV sets off during meal times.
The upright posture improves plantar stepping and alters responses to serotonergic drugs in spinal rats
Authors: Sławińska Urszula , Majczyński Henryk , Dai Yue , Jordan Larry M. 
Published: February 2012

Key points
Locomotor training of rats held in an upright posture has been used recently to restore locomotion after spinal cord injury. Our results show that the upright posture alone improves locomotor recovery in spinal rats.
This improvement is reversed by the removal of cutaneous afferent feedback from the paw, showing that sensory feedback from the foot facilitates the spinal central pattern generator (CPG) for locomotion.
5‐HT2 and 5‐HT1A/7 agonists improve locomotion in the horizontal posture but can impair locomotion in the upright posture, suggesting that a proper balance of afferent feedback from the foot and 5‐HT receptor activation is necessary for optimal locomotor recovery.
Our results provide new insights into the organization of the CPG for locomotion and the evolution of hominid bipedalism. The potent effects of cutaneous afferents from the paw revealed here must be taken into account in the design of strategies to restore locomotion after spinal cord injury.
Contrarily to whey and high protein diets, dietary free leucine supplementation cannot reverse the lack of recovery of muscle mass after prolonged immobilization during ageing
Authors: Magne Hugues , Savary‐Auzeloux Isabelle , Migné Carole , Peyron Marie‐Agnès , Combaret Lydie , Rémond Didier , Dardevet Dominique 
Published: February 2012

Key points
During ageing, there is a lack of recovery of muscle mass following immobilization.
We showed, in old rats, an ‘anabolic resistance’ of muscle protein synthesis to food intake during immobilization and only a slight increase of protein synthesis during the recovery, which explain a poor muscle nitrogen balance that is insufficient to induce a muscle mass gain.
A supplementation with free leucine, an essential amino acid known to stimulate muscle protein metabolism, was efficient in inducing a greater anabolism but failed to induce muscle mass recovery.
This discrepancy was explained by a ‘desynchronization’ between the leucine signal and amino acids coming from dietary protein digestion.
An induction of a larger increase and a longer availability of amino acids in the postprandial state with rich‐protein leucine (i.e. whey) and high protein diets were efficient in inducing a muscle mass recovery after immobilization.
Complete Genome Sequence of a Novel Flavivirus, Duck Tembusu Virus, Isolated from Ducks and Geese in China
Authors: Yun Tao , Zhang Dabing , Ma Xuejun , Cao Zhenzhen , Chen Liu , Ni Zheng , Ye Weicheng , Yu Bin , Hua Jionggang , Zhang Yan , Zhang Cun 
Published: February 2012

ABSTRACT
Duck tembusu virus (DTMUV) is an emerging agent that causes a severe disease in ducks. We report herein the first complete genome sequences of duck tembusu virus strains YY5, ZJ-407, and GH-2, isolated from Shaoxing ducks, breeder ducks, and geese, respectively, in China. The genomes of YY5, ZJ-407, and GH-2 are all 10,990 nucleotides (nt) in length and encode a putative polyprotein of 3,426 amino acids. It is flanked by a 5′ and a 3′ noncoding region (NCR) of 94 and 618 nt, respectively. Knowledge of the whole sequence of DTMUV will be useful for further studies of the mechanisms of virus replication and pathogenesis.
Complete Genome Sequence of a Porcine Epidemic Diarrhea Virus Variant
Authors: Chen Jianfei , Liu Xiaozhen , Shi Da , Shi Hongyan , Zhang Xin , Feng Li 
Published: February 2012

ABSTRACT
In 2011, outbreaks of viral diarrhea were observed on most swine-breeding farms in most of the provinces of China. The disease is characterized by vomiting, severe diarrhea, and a high mortality rate (82.3%) in newborn piglets. The clinical appearance was similar to that of porcine epidemic diarrhea virus (PEDV) infection. PEDVs were detected in samples (feces or small intestines) from most farms. In order to investigate whether there is a PEDV variant circulating in China, we sequenced and analyzed the complete genome of the recently identified field strain, CH/FJND-3/2011. The sequence data indicate that this PEDV variant prevails in China.
Complete Genome Sequence of Pseudomonas aeruginosa Lytic Bacteriophage PA1Ø Which Resembles Temperate Bacteriophage D3112
Authors: Kim Shukho , Rahman Marzia , Kim Jungmin 
Published: February 2012

ABSTRACT

A novel
Pseudomonas aeruginosa
lytic bacteriophage (phage), PA1Ø, was isolated, and its genome was sequenced completely. This phage is able to lyse not only
P. aeruginosa
but also
Staphylococcus aureus
. Genome analysis of PA1Ø showed that it is similar to a
P. aeruginosa
temperate phage, D3112, with the exception of the absence of a
c
repressor-encoding gene, which is known to play a critical role in the maintenance of the lysogenic state of D3112 in
P. aeruginosa
.
Comparing media and family predictors of alcohol use: a cohort study of US adolescents
Authors: Stoolmiller Mike , Wills Thomas A , McClure Auden C , Tanski Susanne E , Worth Keilah A , Gerrard Meg , Sargent James D 
Published: February 2012

ObjectiveTo compare media/marketing exposures and family factors in predicting adolescent alcohol use.DesignCohort study.SettingConfidential telephone survey of adolescents in their homes.ParticipantsRepresentative sample of 6522 US adolescents, aged 10–14 years at baseline and surveyed four times over 2 years.Primary outcome measureTime to alcohol onset and progression to binge drinking were assessed with two survival models. Predictors were movie alcohol exposure (MAE), ownership of alcohol-branded merchandise and characteristics of the family (parental alcohol use, home availability of alcohol and parenting). Covariates included sociodemographics, peer drinking and personality factors.ResultsOver the study period, the prevalence of adolescent ever use and binge drinking increased from 11% to 25% and from 4% to 13%, respectively. At baseline, the median estimated MAE from a population of 532 movies was 4.5 h and 11% owned alcohol-branded merchandise at time 2. Parental alcohol use (greater than or equal to weekly) was reported by 23% and 29% of adolescents could obtain alcohol from home. Peer drinking, MAE, alcohol-branded merchandise, age and rebelliousness were associated with both alcohol onset and progression to binge drinking. The adjusted hazard ratios for alcohol onset and binge drinking transition for high versus low MAE exposure were 2.13 (95% CI 1.76 to 2.57) and 1.63 (1.20 to 2.21), respectively, and MAE accounted for 28% and 20% of these transitions, respectively. Characteristics of the family were associated with alcohol onset but not with progression.ConclusionThe results suggest that family focused interventions would have a larger impact on alcohol onset while limiting media and marketing exposure could help prevent both onset and progression.
Dermatan Sulfate Is Involved in the Tumorigenic Properties of Esophagus Squamous Cell Carcinoma
Authors: Thelin Martin A. , Svensson Katrin J. , Shi Xiaofeng , Bagher Mariam , Axelsson Jakob , Isinger-Ekstrand Anna , van Kuppevelt Toin H. , Johansson Jan , Nilbert Mef , Zaia Joseph , Belting Mattias , Maccarana Marco , Malmström Anders 
Published: February 2012

Abstract
Extracellular matrix, either produced by cancer cells or by cancer-associated fibroblasts, influences angiogenesis, invasion, and metastasis. Chondroitin/dermatan sulfate (CS/DS) proteoglycans, which occur both in the matrix and at the cell surface, play important roles in these processes. The unique feature that distinguishes DS from CS is the presence of iduronic acid (IdoA) in DS. Here, we report that CS/DS is increased five-fold in human biopsies of esophagus squamous cell carcinoma (ESCC), an aggressive tumor with poor prognosis, as compared with normal tissue. The main IdoA-producing enzyme, DS epimerase 1 (DS-epi1), together with the 6-O- and 4-O-sulfotransferases, were highly upregulated in ESCC biopsies. Importantly, CS/DS structure in patient tumors was significantly altered compared with normal tissue, as determined by sensitive mass spectrometry. To further understand the roles of IdoA in tumor development, DS-epi1 expression, and consequently IdoA content, was downregulated in ESCC cells. IdoA-deficient cells exhibited decreased migration and invasion capabilities in vitro, which was associated with reduced cellular binding of hepatocyte growth factor, inhibition of pERK-1/2 signaling, and deregulated actin cytoskeleton dynamics and focal adhesion formation. Our findings show that IdoA in DS influences tumorigenesis by affecting cancer cell behavior. Therefore, downregulation of IdoA by DS-epi1 inhibitors may represent a new anticancer therapy. Cancer Res; 72(8); 1943–52. ©2012 AACR.
miRNA Signatures Associate with Pathogenesis and Progression of Osteosarcoma
Authors: Jones Kevin B. , Salah Zaidoun , Del Mare Sara , Galasso Marco , Gaudio Eugenio , Nuovo Gerard J. , Lovat Francesca , LeBlanc Kimberly , Palatini Jeff , Randall R. Lor , Volinia Stefano , Stein Gary S. , Croce Carlo M. , Lian Jane B. , Aqeilan Rami I. 
Published: February 2012

Abstract
Osteosarcoma remains a leading cause of cancer death in adolescents. Treatment paradigms and survival rates have not improved in two decades. Driving the lack of therapeutic inroads, the molecular etiology of osteosarcoma remains elusive. MicroRNAs (miRNAs) have demonstrated far-reaching effects on the cellular biology of development and cancer. Their role in osteosarcomagenesis remains largely unexplored. Here we identify for the first time an miRNA signature reflecting the pathogenesis of osteosarcoma from surgically procured samples from human patients. The signature includes high expression of miR-181a,miR-181b, and miR-181c as well as reduced expression of miR-16, miR-29b, and miR-142-5p. We also demonstrate that miR-181b and miR-29b exhibit restricted expression to distinct cell populations in the tumor tissue. Further, higher expression of miR-27a and miR-181c* in pre-treatment biopsy samples characterized patients who developed clinical metastatic disease. In addition, higher expression of miR-451 and miR-15b in pre-treatment samples correlated with subsequent positive response to chemotherapy. In vitro and in vivo functional validation in osteosarcoma cell lines confirmed the tumor suppressive role of miR-16 and the pro-metastatic role of miR-27a. Furthermore, predicted target genes for miR-16 and miR-27a were confirmed as down-regulated by real-time PCR. Affymetrix array profiling of cDNAs from the osteosarcoma specimens and controls were interrogated according to predicted targets of miR-16, miR142-5p, miR-29b, miR-181a/b, and miR-27a. This analysis revealed positive and negative correlations highlighting pathways of known importance to osteosarcoma, as well as novel genes. Thus, our findings establish a miRNA signature associated with pathogenesis of osteosarcoma as well as critical pre-treatment biomarkers of metastasis and responsiveness to therapy. Cancer Res; 72(7); 1865–77. ©2012 AACR.
MiR-155 Is a Liposarcoma Oncogene That Targets Casein Kinase-1α and Enhances β-Catenin Signaling
Authors: Zhang Pingyu , Bill Katelynn , Liu Juehui , Young Eric , Peng Tingsheng , Bolshakov Svetlana , Hoffman Aviad , Song Yechun , Demicco Elizabeth G. , Terrada Dolores Lopez , Creighton Chad J. , Anderson Matthew L. , Lazar Alexander J. , Calin George G. , Pollock Raphael E. , Lev Dina 
Published: February 2012

Abstract
Liposarcoma can be an aggressive, debilitating, and fatal malignancy. In this study, we identifed miRNAs associated with the differentiation status of liposarcoma to gain insight into the basis for its progression. miRNA expression profiles determined in human tumors and normal fat specimens identified a dedifferentiated tumor expression signature consisting of 35 miRNAs. Deregulated miRNA expression was confirmed in a second independent sample cohort. The miR-155 was the most overexpressed miRNA and functional investigations assigned an important role in the growth of dedifferentiated liposarcoma cell lines. Transient or stable knockdown of miR-155 retarded tumor cell growth, decreased colony formation, and induced G1-S cell-cycle arrest in vitro and blocked tumor growth in murine xenografts in vivo. We identified casein kinase 1α (CK1α) as a direct target of miR-155 control which enhanced β-catenin signaling and cyclin D1 expression, promoting tumor cell growth. In summary, our results point to important functions for miR-155 and β-catenin signaling in progression of liposarcoma, revealing mechanistic vulnerabilities that might be exploited for both prognostic and therapeutic purposes. Cancer Res; 72(7); 1751–62. ©2012 AACR.