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Synthesis,cytotoxicity assay,and molecular docking study of hydroxychalcone derivatives as potential tyrosinase inhibitors

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Journal of Chinese Pharmaceutical Sciences 2021年第8期30卷 634-644页

作者： aris Stiawan Eti Nurwening Sholikhah Yehezkiel Steven Kumiawan Yoga Priastomo Jumina Department of Chemistry Faculty of Mathematics and Natural SciencesLJniversitas Gadjah MadaSekip UtaraYogyakarta 55281Indonesia Department of Pharmacology and Therapy Faculty of MedicinePublic Health and NursingUniversitas Gadjah MadaSekip UtaraYogyakarta 55281Indonesia Ma Chung Research Center for Photosynthetic Pigments Universitas Ma ChungVilla Puncak TidarN-01Malang 65151Indonesia

In this work,we studied the synthesis,cytotoxicity assay,and molecular docking of hydroxychalcone derivatives as tyrosinase *** of chalcone derivatives was carried out through a Claisen-Schmidt condensation reaction between acetophenone and benzaldehyde derivatives under alkaline conditions for 48 *** synthesized products were characterized by using Fourier transform infrared(FTIR),gas chromatography-mass spectrometry(GC-MS),proton and carbon nuclear magnetic resonance(1H and 13C NMR)*** in vitro inhibitory activity was evaluated against tyrosinase enzyme by employing L-3,4-dihydroxyphenylalanine(L-DOPA)as the *** successfully synthesized 4-hydroxychalcone(HC)and 4-hydroxy-3-methoxychalcone(HMC)with a yield of 60%and 76%,*** the tyrosinase inhibitory test of HC and HMC gave the IC50 value of 64.35 and 21.56μg/mL,respectively,demonstrating that their inhibitory activities against tyrosinase enzyme were better compared with kojic acid and hydroquinone as the positive *** also found that HC gave 2025μg/m L as the IC50 value against Vero cells,confirming that it was not toxic to the normal cell *** molecular docking study gave the root-mean-square deviation value of less than 2?.Furthermore,the binding energies of hydroxychalcone derivatives were found as-30.13 and-31.38 kJ/mol,showing that those compounds could be potentially used as the alternative tyrosinase inhibitors in medical application.

关键词： Hydroxychalcone Cytotoxicity In vitro Molecular docking Tyrosinase inhibitors

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Evaluation of agro-based waste substrates for micropropagule formation in biocontrol fungi,Trichoderma asperellum and ***

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Studies in Fungi 2020年第1期5卷 94-102页

作者： Hasan ZAE Mohd Zainudin NAI aris A Ibrahim MH Yusof MT Department of Biology Faculty of ScienceUniversiti Putra Malaysia43400 Serdang SelangorMalaysia Department of Botany Faculty of ScienceOmar Al Mukhtar UniversityAl BaydaLibya Department of Microbiology Faculty of Biotechnology and Biomolecular SciencesUniversiti Putra Malaysia43400 SerdangSelangorMalaysia

Trichoderma species have shown efficiency on biocontrol of *** commercial application,it must be propagated in mass scale using a cost-effective *** an alternative way to effectively deliver biocontrol fungi inoculum to the field;seven agro-based wastes including rice bran,biochar,empty fruit bunches,coconut fibre,compost,topsoil and mixed soil were used in this study for evaluating mass multiplication of Trichoderma *** on the evaluation of colony-forming units(cfu)among the agro-based waste media used,coconut fibre is the most suitable in promoting the sporulation of Trichoderma asperellum and *** asperellum C1667 showed the higher micropropagule count through incubation period compared to *** *** 120 days on the agro-based waste media,*** C1667 and *** C1675 produced the highest(7.717×10^(5)cfu/g and 6.836±13.79×10^(5)cfu/g)coconut fibres,***,the mixed soil appeared with the lowest *** fibres were shown as a great biocomposting medium for both Trichoderma *** of the present study are valuable for disease management using agro-based wastes as a cost-effective medium for biocontrol agents like Trichoderma species.

关键词： Biocontrol agent mass multiplication shelf life

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Decreasing a-synuclein aggregation by methanolic extract of Centella asiatica in zebrafish Parkinson's model

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Asian Pacific Journal of Tropical Biomedicine 2015年第11期5卷 948-954页

作者： Husnul Khotimah Mulyohadi Ali Sutiman Bambang Sumitro Mochamad aris Widodo Medical Faculty Brawijaya University Laboratory of Pharmacology Medical FacultyBrawijaya University Department of Biology Faculty of ScienceBrawijaya University

Objective: To observe the effects of Centella asiatica(C. asiatica) methanolic extract on a-synuclein aggregation and its expression in rotenone-exposed zebra ***: Zebra fish(Danio rerio) were exposed to 5 m g/L rotenone for 28 days and coincubated with 2.5, 5.0 and 10.0 m g/mL of C. asiatica methanolic extract. The medium was changed every 48 h for maintain the concentration of rotenone and extract. After 28 days zebra fish were sacrificed on the ice block and protein was isolated from zebra fish brain for ELISA of dopamine and Western blotting of a-synuclein. Immunohistochemistry was conducted to observe the a-synuclein expressions from histopathological preparation of zebra fish brain. The head were soaked in 10% formaline for less than 24 h and embedded onto paraffin block, then sliced for immunohistochemistry using anti a-synuclein antibody. We also measured zebra fish motility for 5 min in each ***: C. asiatica has important bioactive compounds such as asiaticoside that has antiin flammatory and antioxidant properties. It may inhibit cascade reaction due to oxidative stress induced by rotenone. Decreasing reactive oxygen species proposed probability of radical attack to a-synuclein protein that caused aggregation and increase of its *** motility of zebra fish was also maintained in C. asiatica groups due to the increasing dopamine level in rotenone-induced zebra fish. High level of reactive oxygen species inactivated enzyme for dopamine synthesis such as tyrosine hydroxylase, and oxidized dopamine itself. Oxidized dopamine increased a-synuclein aggregation. Thus, the dopamine level decreased in rotenone-induced zebra fish, but C. asiatica increased dopamine ***: C. asiatica has a potential to be developed as an anti-Parkinson's disease treatment due to its capability for minimized the sign of Parkinson's such as a-synuclein aggregation and expression, increasing motility and dopamine as well.

关键词： a-Synuclein Centella asiatica Rotenone Parkinson’s

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Mechanism of retinal pericyte migration through Angiopoietin/Tie-2 signaling pathway on diabetic rats

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International Journal of Ophthalmology(English edition) 2018年第3期11卷 375-381页

作者： Nadia Artha Dewi Aulanni'am Aulanni 'am Hidayat Sujuti Muhammad aris Widodo Ojoko Wahono Soeatmadji Department of Ophthalmology Vitreoretinal Subdivision Faculty of Medicine Brawijaya University Malang 65111 Indonesia Department of Biochemistry Faculty of Sciences Brawijaya University Malang 65111 Indonesia Department of Biochemistry Faculty of Medicine Brawijaya University Malang 65111 Indonesia Department of Pharmacology Faculty of Medicine Brawijaya University Malang 65111 Indonesia Department of Endocrinology Faculty of Medicine Brawijaya University Malang 65111 Indonesia

AIM： To investigate the mechanism of pericyte migration through Angiopoietin-2 （Ang-2）/Tie-2 signaling pathway. METHODS： We divided the rats into 5 groups. Each diabetic rat model groups injected with Tie-2 inhibitor, ERK1/2 inhibitor, Akt/PKB inhibitor, and DMSO intravitreal. Retinal digest preparation was done to examine the retinal vasculature including pericyte： endothelial ratio, and morphology of pericyte migration. Tie-2, ERKI/2 and Akt/PKB phosporylation were analyzed by confocal laser scanning microscopy. RESULTS： There was a correlation between pericyte migration with increasing Ang-2 （P〈0.05）. Pericyte number reduced by 40% （1：2.4） after 5wk diabetes on diabetic rats. The pericyte： endothelial ratio on group with Tie-2 inhibitor were 1：1.8. The same result shows on group with Akt/PKB inhibition. ERK1/2 inhibitor group shows the best results of pericyte： endothelial ratio （1：1,7）, Inhibition on Tie-2 receptor decreased the phosphorylation activity of Tie-2, ERK1/2 and Akt/PKB pathway. ERK1/2 inhibition also decreasing the phosphorylation of Tie-2 and Akt/PKB. But on Akt/PKB inhibition, the phosphorylation of Tie-2 and ERK1/2 were relative the same. CONCLUSION： Ang-2 has a role for pericyte migration on diabetic rats through Tie-2 receptor, ERKII2 and Akt/PKB pathways. ERK1/2 is a dominant pathway based on the ability to supress another pathway activity and decreasing pericyte migration on diabetic rats.

关键词： pericyte Angiopoietin/Tie-2 diabetes cellmigration rat

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Last glacial geomorphologic records in Mt Chelmos, North Peloponnesus, Greece

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Journal of Mountain Science 2018年第5期15卷 948-965页

作者： Kosmas PAVLOPOULOS aris LEONTARITIS Constantin D. ATHANASSAS Chara PETRAKOU Dimitris VANDARAKIS Kosnstantinos NIKOLAKOPOILOS Leonidas STAMATOPOULOS Katherina THEODORAKOPOULOU Paris Sorbonne University Abu Dhabi P.O. 38044 Abu Dhabi United Arab Emirates Harokopio University 70 El. Venizelou sir. 17671 Athens Greece Department of Geological Sciences School of Mining and Metallurgical Engineering National Technical University of Athens (NTUA) Zografos Athens 15780 Greece Hellenic Centre for Marine Research 46.7 Ion Athens-Sounio av. P.O. Box 712 Greece University of Patrus Geology Department University Campus 26504 Rio Achaia Greece National and Kapodistrian University of Athens Panepistimioupolis 15784 Ilissia Athens Greece

This study deals with the analysis of the glacial processes that have affected the relief of Mt Chelmos in northern Peloponnesus, Greece during middle and Late Pleistocene. The goal was to compile a combined geomorphological-geological map of the study area which would enable the chronological stratification of the glacial landforms cropping up on Mt. Chelmos. Chronological stratification was further aided by optically stimulated luminescence(OSL)dating. The map served as the basis upon which the reconstruction and discussion on the phases of the Middle-Late Quaternary paleoclimatic history of *** have been made. A sophisticated semiautomated method was first used to analyze the Digital Elevation Model(DEM), combined with Aster,Quickbird and ALOS imagery in order to identify glacial and periglacial, as well as karstic ***, these features along with other nonrecognizable features from the remote-sensing images were documented in the field. In this way, several glacial landforms were identified, such as moraines and cirques, indicating extended glaciation phases during the middle and Late Pleistocene. Additionally,a ground moraine located at an altitude of 1900-2050 m, within the Spanolakos glacial valley, was dated using the OSL-dating method. The resulting ages indicate a phase of glacier advance/stabilization during MIS-5 b(89-86 ka), which is in consistence with pollenrecord evidence from Greece and the *** above the floors of the highest cirques on Mount Tymphi(Hughes 2004). These glacial landforms postdate the youngest moraines on Mount Tymphi(Tymphian Stage MIS 5 d-2), and it has been argued that they might be Younger Dryas in age(Woodward and Hughes 2011) although this has not been confirmed by radiometric dating(Hughes et al. 2006 d).Recent field observations throughout the mountains of central Greece(Leontartitis and Pavlopoulos, unpublished data) demonstrate that the glaciation extent has been underestimated in several

关键词： Semi-automated geomorphologicalmapping Glacial geomorphology Mediterranean OSL dating

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Hepatitis C and renal transplantation in era of new antiviral agents

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World Journal of Transplantation 2018年第4期8卷 84-96页

作者： Maurizio Salvadori aris Tsalouchos Department of Transplantation Renal Unit Careggi University Hospital Nephrology and Dialysis Unit Saints Cosmas and Damian Hospital

Data from World Health Organization estimates that the hepatitis C virus(HCV) prevalence is 3% and approxi-mately 71 million persons are infected worldwide. HCV infection is particularly frequent among patients affected by renal diseases and among those in dialysis treatment. In addition to produce a higher rate of any cause of death, HCV in renal patients and in renal transplanted patients produce a deterioration of liver disease and is a recognized cause of transplant glomerulopathy, new onset diabetes mellitus and lymphoproliferative disorders. Treatment of HCV infection with interferon alpha and/or ribavirin had a poor efficacy. The treatment was toxic, expensive and with limited efficacy. In the post-transplant period was also cause of severe humoral rejection. In this review we have highlighted the new direct antiviral agents that have revolutionized the treatment of HCV both in the general population and in the renal patients. Patients on dialysis or with low glomerular filtration rate were particularly resistant to the old therapies, while the direct antiviral agents allowed achieving a sustained viral response in 90%- 100% of patients with a short period of treatment. This fact to date allows HCV patients to enter the waiting list for transplantation easier than before. These new agents may be also used in renal transplant patients HCV -positive without relevant clinical risks and achieving a sustained viral response in almost all patients. New drug appears in the pipeline with increased profile of efficacy and safety. These drugs are now the object of several phases Ⅱ, Ⅲ clinical trials.

关键词： Hepatitis C virus Renal transplantation Hepatitis C virus and renal diseases Interferon based therapies Direct antiviral agents Hepatitis C viruspositive donors

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Effects of cryoprotectant treatments on bovine sperm function and osmolyte content

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Asian Journal of Andrology 2009年第5期11卷 571-582,I0002,I0003页

作者： Erif E. M. Setyawan[德国] Trevor G. Cooper[德国] Dyah A. Widiasih[德国] aris Junaidi[德国] Ching-Hei Yeung[德国] Centre of Reproductive Medicine and Andrology of the University Clinic Miinster D-48149 Germany Department of Obstetrics and Gynecology Faculty of Veterinary Medicine Gadjah Mada University Yogyakarta 55281Indonesia Department of Public Health Faculty of Veterinary Medicine Gadjah Mada University Yogyakarta 55281 Indonesia

The hypothesis that addition and removal of cryoprotectants to and from spermatozoa would initiate regulatory volume decrease, and lead to osmolyte loss and reduced sperm function, was tested. Common cryoprotectants, in the absence of freezing and thawing, affected bovine ejaculated spermatozoa by lowering their total and progressive motility in medium, reducing their migration through surrogate cervical mucus, damaging sperm head membranes and inducing sperm tail coiling. Sperm function was slightly better maintained after cryoprotectants were added and removed in multiple small steps rather than in a single step. The intracellular content of the polyol osmolytes, D-sorbitol and myo-inositol, exceeded that of the zwitterion osmolytes, L-carnitine and L-glutamate. Certain cryoprotectants reduced intracellular L-camitine and L-glutamate concentration but not that of myo-inositol or D-sorbitol. Multistep treatments with some cryoprotectants had advantages over one-step treatments in mucus penetration depending on the original amount of intracellular camitine and glutamate in the spermatozoa. Overall, sperm quality was best maintained by multistep treatment with glycerol and propanediols that were associated with decreased intracellular glutamate concentration. Bovine spermatozoa seem to use glutamate to regulate cryoprotectant-induced cell swelling.

关键词： cryoconservation cryoprotectants osmotic swelling regulatory volume decrease

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Pharmacogenetics of immunosuppressant drugs:A new aspect for individualized therapy

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World Journal of Transplantation 2020年第5期10卷 90-103页

作者： Maurizio Salvadori aris Tsalouchos Department of Renal Transplantation Careggi University HospitalFlorence 50139Italy Nephrology and Dialysis Unit Saints Cosmas and Damian HospitalPescia 51017Italy

In recent years,pharmacogenetics has emerged as an important tool for choosing the right immunosuppressant drug and its appropriate ***,pharmacogenetics may exert its action on immunosuppressant drugs at three *** identifies and studies the genes involved in encoding the proteins involved in drug pharmacokinetics and in encoding the enzymes involved in drug *** is also relevant in encoding the enzymes and proteins involved in codifying the transmembrane proteins involved in transmembrane passage favoring the absorption and intracellular action of several *** concern the variability of genes encoding the proteins involved as immunosuppressant triggers in the pharmacodynamic *** course,not all genes have been discovered and studied,but some of them have been clearly examined and their relevance together with other factors such as age and race has been *** genes on the basis of relevant studies have been proposed as good candidates for future ***,to date,clear conclusions may be drawn only for those drugs that are metabolized by CYP3A5 and its genotyping before kidney,heart and lung transplantation is *** conclusions of the studies on the recommended candidate genes,together with the development of omics techniques could in the future allow us to choose the right dose of the right immunosuppressant for the right patient.

关键词： Immunosuppressant pharmacokinetics Immunosuppressant pharmacodynamics Immunosuppressant pharmacogenetics Immunosuppressant pharmacogenomics Transplantation Immunosuppressant drugs

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Immunoglobulin G4-related kidney diseases: An updated review

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World Journal of Nephrology 2018年第1期7卷 29-40页

作者： Maurizio Salvadori aris Tsalouchos Renal Unit Department of Transplantation Careggi University Hospital Division of Nephrology Nephrology and Dialysis Unit Saints Cosmas and Damian Hospital

This review will encompass definition, pathogenesis, renal clinical manifestations and treatment of immunoglobulin G4-related diseases( IgG4-RDs). IgG4-RD is a recently recognized clinical entity that often involves multiple organs and is characterized by high levels of serum immunoglobulins G4, dense infiltration of IgG4+ cells and storiform fibrosis. Cellular immunity, particularly T-cell mediated immunity, has been implicated in the pathogenesis of IgG4-RDs. The most frequent renal manifestations of IgG4-RD are IgG4-related tubulointerstitial nephritis, membranous glomerulopathy and obstructive nephropathy secondary to urinary tract obstruction due to IgG4-related retroperitoneal fibrosis. IgG4-RD diagnosis should be based on specific histopathological findings, confirmed by tissue immunostaining, typical radiological findings and an appropriate clinical context. The first line treatment is the steroids with two warnings: Steroid resistance and relapse after discontinuation. In the case of steroid resistance, B cell depleting agents as rituximab represent the secondline treatment. In the case of relapse after discontinuation, steroid treatment may be associated with steroid sparing agents. Since the disease has been only recently identified, more prospective, long-term studies are needed to an improved understanding and a more correct and safe treatment.

关键词： Immunoglobulin G4-related disease Storiform fibrosis Lymphoplasmacytic infiltration Tubulointerstitial nephritis Steroid treatment B cell depleting agents

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Biomarkers in renal transplantation:An updated review

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World Journal of Transplantation 2017年第3期7卷 161-178页

作者： Maurizio Salvadori aris Tsalouchos Renal Unit Department of TransplantationCareggi University Hospital Division of Nephrology Careggi University Hospital

Genomics, proteomics and molecular biology lead to tremendous advances in all fields of medical sciences. Among these the finding of biomarkers as non invasiveindicators of biologic processes represents a useful tool in the field of transplantation. In addition to define the principal characteristics of the biomarkers, this review will examine the biomarker usefulness in the different clinical phases following renal transplantation. Biomarkers of ischemia-reperfusion injury and of delayed graft function are extremely important for an early diagnosis of these complications and for optimizing the treatment. Biomarkers predicting or diagnosing acute rejection either cell-mediated or antibody-mediated allow a risk stratification of the recipient, a prompt diagnosis in an early phase when the histology is still unremarkable. The kidney solid organ response test detects renal transplant recipients at high risk for acute rejection with a very high sensitivity and is also able to make diagnosis of subclinical acute rejection. Other biomarkers are able to detect chronic allograft dysfunction in an early phase and to differentiate the true chronic rejection from other forms of chronic allograft nephropathies no immune related. Finally biomarkers recently discovered identify patients tolerant or almost tolerant. This fact allows to safely reduce or withdrawn the immunosuppressive therapy.

关键词： Renal transplantation Biomarkers Genomic Proteomics Transplant outcome Molecular signatures

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