Molecular insights to explore abietane diterpenes as new LOX inhibitors

Lipoxygenase (LOX) inhibitors are well known for their anti-inflammatory effects derived from both natural products and synthetic sources. Taxus wallichiana Zucc is traditionally used in the treatment of various diseases including inflammation. In a recent study, it was used to conduce the isolation of the bioactive compounds from Taxus wallichiana Zucc. thanks to its ethnopharmacological use in diseases including inflammation. Phytochemical studies lead to the isolation of abietane diterpenoids, namely Taxusabietane C (TC) and Taxamairin F (TF). Test compounds showed significant LOX inhibitory effects. IC₅₀ values of TC and TF were 69 ± 0.31 and 73 ± 0.14 μM, respectively. The standard compound Baicalein and Tenidap sodium showed the IC₅₀ value being 22.1 ± 0.03 and 41.6 ± 0.02 μM. Significant LOX inhibitory activities were supported by a molecular docking simulation to explore molecular interactions of the compounds with the active (catalytic) site of LOX.     

The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story,yet mesmerizing

The prevalence of colorectal cancer (CRC) has markedly increased worldwide in the last decade. Alterations of bile acid metabolism and gut microbiota have been reported to play vital roles in intestinal carcinogenesis. About trillions of bacteria have inhabited in the human gut and maintained the balance of host metabolism. Bile acids are one of numerous metabolites that are synthesized in the liver and further metabolized by the gut microbiota, and are essential in maintaining the normal gut microbiota and lipid digestion. Multiple receptors such as FXR, GPBAR1, PXR, CAR and VDR act as sensors of bile acids have been reported. In this review, we mainly discussed interplay between bile acid metabolism and gut microbiota in intestinal carcinogenesis. We then summarized the critical role of bile acids receptors involving in CRC, and also addressed the rationale of multiple interventions for CRC management by regulating bile acids–microbiota axis such as probiotics, metformin, ursodeoxycholic acid and fecal microbiota transplantation. Thus, by targeting the bile acids–microbiota axis may provide novel therapeutic modalities in CRC prevention and treatment.     

Treatment of chronic hepatitis delta virus with peg-interferon and factors that predict sustained viral response

AIM:To observe the efficacy of peg-interferon in the treatment of hepatitis delta virus(HDV) and to identify the factors that would be predictive of the sustained viral response(SVR).METHODS:This prospective study was conducted in Medical Unit Ⅳ of the Liaquat University of Medical and Health Sciences Hospital Jamshoro from June 2008 to September 2011.This study cohort included all patients of either sex who presented during this time with hepatitis B surface antigen positivity,hepatitis B virus DNA 20 000 IU/mL,serum glutamic pyruvic transaminase(SGPT) 2(upper limit of normal),HDV-RNA positivity with fibrosis stage ≥ 2.Informed consent was obtained from each of these individuals.Patients were diagnosed with hepatitis D on the basis of detectable viral antibodies and the presence of HDV-RNA in their serum.A liver biopsy was performed in all cases and fibrosis staging was performed in accordance with the METAVIR scoring system.All eligible patients were administered peg-interferon at a weekly dosage of 1.5 g/kg body weight for 48 wk.HDV-RNA was assayed at the end of this treatment period and again at 24 wk later.A biochemical response was determined by a normalization of SGPT at the end of the treatment or during follow up.The end of treatment response was defined by a HDV-RNA negative status.A sustained virological response was defined by undetectable serum HDV-RNA at six months after the end of treatment.RESULTS:Among the 277 patients enrolled in our present study,238 completed a course of peg-interferon therapy of which 180(75.6%) were male and 58(24.4%) female.Biochemical responses were achieved in 122/238(51.3%) patients.End of treatment responses were achieved in 71/238(29.8%) cases.A SVR was achieved in 70 of these patients(29.4%).A strong association was found between the SVR and the end of treatment responses(P = 0.001),biochemical responses(P = 0.001) and the degree of fibrosis(P = 0.002).CONCLUSION:Peg-interferon therapy can induce remission in nearly one third of patients harboring HDV.     

Unusual presentations of foreign body in aerodigestive tract

Foreign bodies lodged in aerodigestive tract makes the commonest emergency in the otorhinolaryngology clinics. Diagnosis often becomes difficult with parental ignorance and lack of clear history. Patients with foreign body can have unusual presentations.     

Infectious bronchitis virus and brown shell colour: Australian strains of infectious bronchitis virus affect brown eggshell colour in commercial laying hens differently

The aim of the current study was to assess any effect of wild and vaccine Australian infectious bronchitis virus (IBV) strains on shell colour in brown-shelled eggs. In Experiment 1, eggs were collected from day 1 to day 13 post-inoculation (p.i.) from unvaccinated laying hens challenged with IBV wild strains T and N1/88 and from a negative control group of hens. In Experiment 2, eggs were collected from 2 to 22 days p.i. from unvaccinated and vaccinated laying hens challenged with either a wild or a vaccine strain of IBV. In Experiment 1, there was a significant effect (P?相似文献   

Self-assembled supramolecular thermoreversible β-cyclodextrin/ethylene glycol injectable hydrogels with difunctional Pluronic®127 as controlled delivery depot of curcumin. Development,characterization and in vitro evaluation

This study aimed to design a novel thermoreversible compact self-assembled host macromolecule based on β-cyclodextrin and low molecular weight ethylene glycol with a difunctional guest molecule i.e. poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) tri-block co-polymer (Pluronic^® 127) through host-guest inclusion complexation in aqueous media using cold method. The injectable thermoreversible self-assembled supramolecular hydrogel was developed to encapsulate hydrophobic curcumin as anti-malignant agent and for controlled delivery to systemic circulation after in vivo application through subcutaneous route. As reversible supramolecular assembly, the thermoresponsive gels showed a unique structure-related reversible gel to sol transition above and below LCST determined via tube titling method. The rheological measurements of the supramolecular hydrogels showed a viscoelastic structure. Optical transmittance of supramolecular assembly also confirmed the thermoreversible sol–gel transitions. The strong potential of supramolecular assembly as injectable controlled delivery was assessed using curcumin as model active pharmaceutical ingredient for in vitro release experiments. The release experiments conducted in various dissolution medias and at different temperature programs showed maximum curcumin release in phosphate buffer solution (7.4) at 35 °C. methyl thiazolyl tetrazolium assay was used to assess the safety and efficacy of self-assembled supramolecular injectable hydrogels. In vitro cytotoxicity study showed that blank supramolecular gels are non-toxic to the L929 cells. While curcumin released from supramolecular injectable hydrogels (Cur-β-CD/EG-PF127) has the ability to show pharmacological activity and kill the cancer cells. Furthermore the formation of channel type inclusion complex was studied through Fourier transformed infra-red spectroscopy, X-ray diffraction, thermogravimetric analysis, differential scanning calorimetric and scanning electron microscopic analysis.