MoDeSuS: A Machine Learning Tool for Selection of Molecular Descriptors in QSAR Studies Applied to Molecular Informatics

The selection of the most relevant molecular descriptors to describe a target variable in the context of QSAR (Quantitative Structure-Activity Relationship) modelling is a challenging combinatorial optimization problem. In this paper, a novel software tool for addressing this task in the context of regression and classification modelling is presented. The methodology that implements the tool is organized into two phases. The first phase uses a multiobjective evolutionary technique to perform the selection of subsets of descriptors. The second phase performs an external validation of the chosen descriptors subsets in order to improve reliability. The tool functionalities have been illustrated through a case study for the estimation of the ready biodegradation property as an example of classification QSAR modelling. The results obtained show the usefulness and potential of this novel software tool that aims to reduce the time and costs of development in the drug discovery process.

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New Platinum(IV) and Palladium(II) Transition Metal Complexes of s-Triazine Derivative: Synthesis, Spectral, and Anticancer Agents Studies

New Pd(II) and Pt(IV) triazine complexes [Pt3(L1)2(Cl)9(H2O)3].3Cl.3H2O (1), [Pt3(L2)2(Cl)9(H2O)3].3Cl (2), [Pt3(L3)2(Cl)9(H2O)3].3Cl (3), [Pt2(L4)2(Cl)6(H2O)2] .2Cl.4H2O (4), [Pd3(L1)2(H2O)6] .3Cl2 (5), [Pd3(L2)2(H2O)6].3Cl2 (6), [Pd3(L3)2(H2O)6].3Cl2 (7), and [Pd2(L4)2(H2O)4].2Cl2 (8) were synthesized and well characterized using elemental analyses, molar conductance, IR, UV-Vis, magnetic susceptibility, 1H, 13C-NMR spectra, and thermal analyses. These analyses deduced that the L1, L2, and L3 ligands act as tridentate forming octahedral geometry with Pt(IV) metal ions and square planar geometry in case of Pd(II) complexes but the L4 ligand acts as bidentate chelate. The molar conductance values refer to the fact that all the prepared s-triazine complexes have electrolyte properties which are investigated in DMSO solvent. Surface morphology behaviors of prepared complexes have been scanned using TEM. The crystalline behavior of triazine complexes has been checked based on X-ray powder diffraction patterns. The antimicrobial activity of the free ligands and their platinum(IV) and palladium(II) complexes against the species Staphylococcus aureus (G+), Escherichia coli (G−), Aspergillus flavus, and Candida albicans has been carried out and compared with the standard one. The coordination of ligands towards metal ions makes them stronger bacteriostatic agents, thus inhibiting the growth of bacteria and fungi more than the free ligands. The cytotoxic assessment IC50 of the free ligands and its platinum(IV) complexes in vitro against human colon and lung cancer cell lines introduced a promising efficiency.

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Gastroprotective Effects of Plants Extracts on Gastric Mucosal Injury in Experimental Sprague-Dawley Rats

Rubus crataegifolius (black raspberry, RF), Ulmus macrocarpa (elm, UL), and Gardenia jasminoides (cape jasmine, GJ) are well known for hundreds of years as folk medicines in China and Korea to treat various gastrointestinal disturbance. The present study evaluated the gastroprotective effects of these plants either single or in combination against HCl/EtOH-induced gastritis and indomethacin-induced ulcer in rat model. Stomach ulcer was induced by oral ingestions of HCl/EtOH or indomethacin. Treatment with RF, UL, and GJ separately or in combination was done 1 h before ulcer induction. On HCl/EtOH-induced gastritis RF, UL, and GJ at a dose of 150 mg/kg showed comparable antigastritis effect (less than 50% inhibition) with lesion index of 94.97±8.05, 108.48±11.51, and 79.10±9.77 mm compared to cimetidine (45.33±23.73 mm). However, the combination of RF, UL, and GJ at a dose of 150 mg/kg with a ratio of 50:50:50 showed remarkable antigastritis effect with 77% inhibition. The observed lesion index at a ratio of 50:50:50 was 23.34±9.11 mm similar to cimetidine (18.88±19.88 mm). On indomethacin-induced ulcer, RF and GJ showed 38.28% and 51.8% inhibition whereas UL showed around 17.73% inhibition at 150 mg/kg. Combination of RF, UL, and GJ at 150 mg/kg showed strong antigastritis effect with 83.71% inhibition. These findings suggest strong gastroprotective effect of combined extract. In addition, these plants showed significant antioxidant activity in DPPH scavenging assay and antilipid peroxidation activity. Combination of black raspberry, elm, and cape jasmine might be a significant systemic gastroprotective agent that could be utilized for the treatment and/or protection of gastritis and gastric ulcer.

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The Green Synthesis of MgO Nano-Flowers Using Rosmarinus officinalis L. (Rosemary) and the Antibacterial Activities against Xanthomonas oryzae pv. oryzae

Recently, the use of herbs in the agriculture and food industry has increased significantly. In particular, Rosmarinus officinalis L. extracts have been reported to have strong antibacterial properties, which depend on their chemical composition. The present study displayed a biological method for synthesis of magnesium oxide (MgO) nano-flowers. The nano-flowers are developed without using any catalyst agent. Aqueous Rosemary extract was used to synthesize MgO nano-flowers (MgONFs) in stirring conditions and temperature at 70°C for 4 h. The mixture solution was checked by UV-Vis spectrum to confirm the presence of nanoparticles. The MgO nano-flowers powder was further characterized in this study by the X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy. In addition, bacteriological tests indicated that MgO nano-flowers significantly inhibited bacterial growth, biofilm formation, and motility of Xanthomonas oryzae pv. oryzae, which is the causal agent of bacterial blight disease in rice. The electronic microscopic observation showed that bacterial cell death may be mainly due to destroy of cell integrity, resulting in leakage of intracellular content. As recommended, the use of Rosemary extract is an effective and green way to produce the MgO nano-flowers, which can be widely used in agricultural fields to suppress bacterial infection.

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Reduced Patient-Reported Outcome Scores Associate with Level of Fibrosis in Patients with Nonalcoholic Steatohepatitis

Patient-reported outcomes (PROs) are used to measure patients' experience with their disease. However, there are few PRO data from patients with NASH. We collected data from the STELLAR clinical trials to assess PROs for NASH and advanced fibrosis.

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Cell Therapies for Parkinson's Disease

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Enrichment of CLDN18‐ARHGAP fusion gene in gastric cancers in young adults

Summary

Gastric cancer in young adults has been pointed out to comprise a subgroup associated with distinctive clinicopathological features, including an equal gender distribution, advanced disease and diffuse‐type histology. Comprehensive molecular analyses of gastric cancers have led to molecular‐based classifications and to specific and effective treatment options available. The molecular traits of gastric cancers in young adults await investigations, which should provide a clue to explore therapeutic strategies. Here we studied 146 gastric cancer patients diagnosed at the age of less than 40 years old at the Cancer Institute Hospital. Tumor specimens were examined for Helicobacter pylori infection, Epstein‐Barr virus positivity, and for the expression of mismatch repair genes to indicate microsatellite instability. Overexpression, gene amplifications and rearrangements of 18 candidate driver genes were examined by immunohistochemistry and fluorescence in situ hybridization. Besides small number of cases positive for Epstein‐Barr virus and microsatellite instability (n=2, each), we repeatedly found tumors having gene fusion between a tight‐junction protein claudin CLDN18 and a regulator of small G proteins ARHGAP in as many as 22 cases (15.1%), and RNA sequencing identified two novel types of the fusion. Notably, patients with the CLDN18‐ARHGAP fusion revealed association with aggressive disease and poor prognosis, even when grouped by their clinical stages. These observations indicate that a fusion gene between CLDN18 and ARHGAP is enriched in younger age‐onset gastric cancers, and its presence may contribute to their aggressive characteristics.

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