MOLECULAR DOCKING STUDIES OF MAGE INHIBITORS IN THE TREATMENT OF LUNG CANCER

The insilico methods for drug discovery are becoming increasingly powerful and useful. That in combination with increasing computer processor power. Lung cancer is the leading cause of cancer associated deaths Worldwide and has one of the poorest prognoses among all cancer types. A variety of melanoma antigen A (MAGE-A) genes are commonly detected in non-small cell lung cancers. Their biological function is not well characterized but may involve the regulation of apoptosis and cell cycle progression. In this study  ligand-based drug design were employed to design novel MAGE inhibitors from  Naringi crenulata found in  Asia. The MAGE structure model was built in homology modelling based on known receptors of the same family.  A phytochemicals of Naringi crenulata are analysed and optimized with the Arguslab to investigate the interactions between the target compounds and the amino acid residues of the Mage protein .All the compound have shown binding pose  between  from – 6.54 to -15.34.out of five compound 1,2-benzenedicarboxylic acid show best ligand energy -8.15Kcal/mol with  3 hydrogen  bond  of distance is 2.1,3.0 and 2.3               Key Words: Lung Cancer, Mage Protein, Docking, Modelling, Naringi Crenulata,Argus la

PHYTOSYNTHESIS OF SILVER NANOPARTICLES USING HYGROPHILA AURICULATA LEAF EXTRACT AND ASSESSMENT OF THEIR ANTIBACTERIAL AND ANTIOXIDANT PROPERTIES

Objective: In this study, the phytosynthesis of silver nanoparticles (AgNPs) using leaf extracts of Hygrophila auriculata (HA) and their biological activities was investigated.Methods: The synthesis of AgNPs was done by using the green synthetic method and analyzed by UV-Visible spectroscopy, X-ray diffraction (XRD), fourier transform infrared spectroscopy (FTIR) and further characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The antibacterial activity of HA AgNPs was studied by agar well diffusion method and micro broth dilution method for determination of minimum inhibitory concentration (MIC). The antioxidant potentials of HA AgNPs were detected by Diphenyl-1-picryl hydrazyl radical scavenging assay (DPPH), Phosphomolybdenum assay, reducing power assay.Results: The prepared HA AgNPs showed characteristic absorption peak at 420 nm in the UV-Vis spectrum. FTIR spectra had shown that the biomolecules present in leaf extract were responsible for the reduction and capping material of silver nanoparticles. XRD study showed the particles found to be crystalline in nature, with a face-centered cubic (fcc) structure. TEM and DLS results revealed that the AgNPs were mostly spherical with an average size ranging from ~15-115 nm with a mean diameter of 40.96 nm. The HA AgNPs showed good antibacterial activity and MIC against Staphylococcus aureus (ATCC 6538), Bacillus cereus (NCIM 2106), Pseudomonas aeruginosa (ATCC 9027) and Escherichia coli (ATCC 8739). In agar well diffusion method, the maximum zone of inhibition was found against Pseudomonas aeruginosa (ATCC 9027) with 18 mm and minimum zone of inhibition was found to be against Escherichia coli (ATCC 8739) with 13 mm. The MIC of the HA AgNp was found to be 5µg against all the test organisms. In addition, the Diphenyl-1-picryl hydrazyl radical scavenging assay (DPPH), Phosphomolybdenum assay, reducing power assay revealed they can be used as the potential scavenger against deleterious damages caused by the free radicals.Conclusion: The present study explored that Hygrophila auriculata which are efficient producers of AgNPs and could act as safe and cost-effective with potential antibacterial and antioxidant activities. These findings encourage studying HA AgNP further for their potential biological applications

Hydrodynamics of thermal granular convection

A hydrodynamic theory is formulated for buoyancy-driven ("thermal") granular convection, recently predicted in molecular dynamic simulations and observed in experiment. The limit of a dilute flow is considered. The problem is fully described by three scaled parameters. The convection occurs via a supercritical bifurcation, the inelasticity of the collisions being the control parameter. The theory is expected to be valid for small Knudsen numbers and nearly elastic grain collisions.Comment: 4 pages, 4 EPS figures, some details adde

Diagnosis of biliary tract and ampullary carcinomas

Diagnostic methods for biliary tract carcinoma and the efficacy of these methods are discussed. Neither definite methods for early diagnosis nor specific markers are available in this disease. When this disease is suspected on the basis of clinical symptoms and risk factors, hemato-biochemical examination and abdominal ultrasonography are performed and, where appropriate, enhanced computed tomography (CT) and/or magnetic resonance cholangiopancreatography (MRCP) is carried out. Diagnoses of extrahepatic bile duct cancer and ampullary carcinoma are often made based on the presence of obstructive jaundice. Although rare, abdominal pain and pyrexia, as well as abnormal findings of the hepatobiliary system detected by hemato-biochemical examination, serve as a clue to making a diagnosis of these diseases. On the other hand, the early diagnosis of gallbladder cancer is scarcely possible on the basis of clinical symptoms, so when this cancer is found with the onset of abdominal pain and jaundice, it is already advanced at the time of detection, thus making a cure difficult. When gallbladder cancer is suspected, enhanced CT is carried out. Multidetector computed tomography (MDCT), in particular — one of the methods of enhanced CT — is useful for decision of surgical criteria, because MDCT shows findings such as localization and extension of the tumor, and the presence or absence of remote metastasis. Procedures such as magnetic resonance imaging, endoscopic ultrasonography, bile duct biopsy, and cholangioscopy should be carried out taking into account indications for these procedures in individual patients. However, direct biliary tract imaging is necessary for making a precise diagnosis of the horizontal extension of bile duct cancer

Flowcharts for the management of biliary tract and ampullary carcinomas

No strategies for the diagnosis and treatment of biliary tract carcinoma have been clearly described. We developed flowcharts for the diagnosis and treatment of biliary tract carcinoma on the basis of the best clinical evidence. Risk factors for bile duct carcinoma are a dilated type of pancreaticobiliary maljunction (PBM) and primary sclerosing cholangitis. A nondilated type of PBM is a risk factor for gallbladder carcinoma. Symptoms that may indicate biliary tract carcinoma are jaundice and pain in the upper right area of the abdomen. The first step of diagnosis is to carry out blood biochemistry tests and ultrasonography (US) of the abdomen. The second step of diagnosis is to find the local extension of the carcinoma by means of computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), percutaneous transhepatic cholangiography (PTC), and endoscopic retrograde cholangiopancreatography (ERCP). Because resection is the only way to completely cure biliary tract carcinoma, the indications for resection are determined first. In patients with resectable disease, the indications for biliary drainage or portal vein embolization (PVE) are checked. In those with nonresectable disease, biliary stenting, chemotherapy, radiotherapy, and/or best supportive care is selected

Association of variants in the SPTLC1 gene with juvenile amyotrophic lateral sclerosis

IMPORTANCE Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.OBJECTIVE To identify the genetic variants associated with juvenile ALS.DESIGN, SETTING, AND PARTICIPANTS In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.MAIN OUTCOMES AND MEASURES De novo variants present only in the index case and not in unaffected family members.RESULTS Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p. Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.CONCLUSIONS AND RELEVANCE These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.Genetics of disease, diagnosis and treatmen

Common mode behavior in grid connected DC and AC decoupled PV Inverter topologies

The transformer-less grid connected inverters are gaining more popularity due to their high efficiency, very low ground leakage current and economic feasibility especially in photovoltaic systems. The major issue which surfaces these systems is that of common mode leakage current which arises due to the absence of an electrical transformer connected between the inverter and the utility grid. Several topologies have evolved to reduce the impact of common mode leakage current and a majority of them have succeeded in eliminating the impacts and have well kept them within the limits of grid standards. This paper compares and analyses the impact of the common mode leakage current for four popular inverter configurations through simulation of the topologies such as H5, H6, HERIC and FBZVR inverters