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Impact of sodium glucose cotransporter-2 inhibitors on liver steatosis/fibrosis/inflammation and redox balance in non-alcoholic fatty liver disease

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World Journal of Gastroenterology 2022年第26期28卷 3243-3257页

作者： Francesco Bellanti Aurelio Lo Buglio MichałDobrakowski Aleksandra kasperczyk Sławomir kasperczyk Palok Aich Shivaram P Singh Gaetano Serviddio Gianluigi Vendemiale Department of Medical and Surgical Sciences University of FoggiaFoggia 71122Italy Department of Biochemistry Medical University of Silesia in KatowiceZabrze 41-808Poland School of Biological Sciences National Institute of Science Education and ResearchKhurdha 752050India Department of Gastroenterology SCB Medical CollegeCuttack 753007India

BACKGROUND Sodium glucose cotransporter-2 inhibitors(SGLT2-I)are the most recently approved drugs for type 2 diabetes(T2D).Recent clinical trials of these compounds reported beneficial cardiovascular(CV)and renal outcomes.A major cause of vascular dysfunction and CV disease in diabetes is hyperglycemia associated with inflammation and oxidative stress.Pre-clinical studies demonstrated that SGLT2-I reduce glucotoxicity and promote anti-inflammatory effects by lowering oxidative stress.AIM To investigate the effects of SGLT2-I on markers of oxidative stress,inflammation,liver steatosis,and fibrosis in patients of T2D with non-alcoholic fatty liver disease(NAFLD).METHODS We referred fifty-two consecutive outpatients treated with metformin monotherapy and exhibiting poor glycemic control to our centre.We introduced the outpatients to an SGLT2-I(dapagliflozin,empagliflozin,or canagliflozin;n=26)or a different hypoglycemic drug[other glucose-lowering drugs(OTHER),n=26].We evaluated circulating interleukins and serum hydroxynonenal(HNE)-or malondialdehyde(MDA)-protein adducts,fatty liver index(FLI),NAFLD fibrosis score,aspartate aminotransferase(AST)/alanine aminotransferase(ALT)ratio,AST-to-platelet-ratio index(APRI),and fibrosis-4 on the day before(T0)and following treatment for six months(T1).We also performed transient elastography at T0 and T1.RESULTS Add-on therapy resulted in improved glycemic control and reduced fasting blood glucose in both groups.Of note,following treatment for six months,a reduction of FLI and APRI,as well as of the FibroScan result,was reported in patients treated with SGLT2-I,but not in the OTHER group;furthermore,in the SGLT2-I group,we reported lower circulating levels of interleukin(IL)-1β,IL-6,tumor necrosis factor,vascular endothelial growth factor,and monocyte chemoattractant protein-1,and higher levels of IL-4 and IL-10.We did not observe any modification in circulating interleukins in the OTHER group.Finally,serum HNE-and MDA-protein adducts decreased significantly in SGLT2-I rather

关键词： Sodium glucose cotransporter-2 inhibitors Non-alcoholic fatty liver disease Oxidative stress Type 2 diabetes Liver fibrosis Inflammation

Environmental exposure to cadmium but not lead is associated with decreased semen quality parameters:quality regionalism of sperm properties

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Asian Journal of Andrology 2022年第1期24卷 26-31页

作者： Katarzyna Olszak-Wasik Andrzej Tukiendorf Aleksandra kasperczyk Artur Wdowiak Stanislaw Horak Department of Gynecology Obstetrics and Oncological Gynecology in BytomMedical University of SilesiaSchool of Medicine and Division of Dentistry in ZabrzeBatorego 15Bytom 41-902Poland Department of Public Health Wroclaw Medical UniversityBartla 5Wroclaw 51-618Poland Department of Biochemistry Medical University of SilesiaSchool of Medicine and Division of Dentistry in ZabrzeJordana 19Zabrze 41-808Poland Faculty of Health Sciences Diagnostic Techniques UnitMedical University of LublinStaszica 4/6Lublin 20-081Poland

Environmental factors may negatively contribute to a progressive worsening of semen quality,and differences in semen quality may result from different environmental exposures(regional differences)or lifestyle differences.Heavy metals are factors with a confirmed negative influence on male fertility.Among them,lead and cadmium are commonly found in human surroundings.Thus,we analyzed semen parameters(according to the World Health Organization 2010 recommendations)and semen lead and cadmium concentrations in 188 men from two different regions in Poland,a typical agricultural area and an industrial area,in couples that had been diagnosed with infertility.The assays were performed using flameless electrothermal atomic absorption spectrometry.In the statistical analysis,regional comparisons and then taxonomic comparisons based on three parameters(age,semen concentration,and sperm morphology)were applied.We showed that more cadmium than lead accumulated in semen,a higher cadmium concentration was observed in semen obtained from men from the agricultural region,and better semen quality and lower cadmium concentrations were found in the semen of men from the industrial,more polluted region.We thus showed an existing regionalism in the sperm quality properties.However,semen parameters such as morphology and progressive and nonprogressive motility followed the same trends,regardless of the patient’s age,region,or class.We could conclude that the environment has a minor impact on sperm morphology and progressive and nonprogressive motility and that other existing factors could have an indirect influence on semen quality.

关键词： cadmium environment lead semen quality taxonomic analysis

Impact of senescence on the transdifferentiation process of human hepatic progenitor-like cells

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World Journal of Stem Cells 2021年第10期13卷 1595-1609页

作者： Francesco Bellanti Giorgia di Bello Rosanna Tamborra Marco Amatruda Aurelio Lo Buglio MichałDobrakowski Aleksandra kasperczyk Sławomir kasperczyk Gaetano Serviddio Gianluigi Vendemiale Department of Medical and Surgical Sciences University of FoggiaFoggia 71122Italy Department of Biochemistry Medical University of SilesiaZabrze 41-808Poland

BACKGROUND Senescence is characterized by a decline in hepatocyte function,with impairment of metabolism and regenerative capacity.Several models that duplicate liver functions in vitro are essential tools for studying drug metabolism,liver diseases,and organ regeneration.The human HepaRG cell line represents an effective model for the study of liver metabolism and hepatic progenitors.However,the impact of senescence on HepaRG cells is not yet known.AIM To characterize the effects of senescence on the transdifferentiation capacity and mitochondrial metabolism of human HepaRG cells.METHODS We compared the transdifferentiation capacity of cells over 10(passage 10[P10])vs P20.Aging was evaluated by senescence-associated(SA)beta-galactosidase activity and the comet assay.HepaRG transdifferentiation was analyzed by confocal microscopy and flow cytometry(expression of cluster of differentiation 49a[CD49a],CD49f,CD184,epithelial cell adhesion molecule[EpCAM],and cytokeratin 19[CK19]),quantitative PCR analysis(expression of albumin,cytochrome P4503A4[CYP3A4],γ-glutamyl transpeptidase[γ-GT],and carcinoembryonic antigen[CEA]),and functional analyses(albumin secretion,CYP3A4,andγ-GT).Mitochondrial respiration and the ATP and nicotinamide adenine dinucleotide(NAD^(+))/NAD with hydrogen(NADH)content were also measured.RESULTS SAβ-galactosidase staining was higher in P20 than P10 HepaRG cells;in parallel,the comet assay showed consistent DNA damage in P20 HepaRG cells.With respect to P10,P20 HepaRG cells exhibited a reduction of CD49a,CD49f,CD184,EpCAM,and CK19 after the induction of transdifferentiation.Furthermore,lower gene expression of albumin,CYP3A4,andγ-GT,as well as reduced albumin secretion capacity,CYP3A4,andγ-GT activity were reported in transdifferentiated P20 compared to P10 cells.By contrast,the gene expression level of CEA was not reduced by transdifferentiation in P20 cells.Of note,both cellular and mitochondrial oxygen consumption was lower in P20 than in P10 transdifferentiated cells.Finally,both ATP and NAD^

关键词： Senescence HepaRG cells Transdifferentiation Mitochondria Regeneration Nicotinamide adenine dinucleotide

Influence of the Type of Fertilization on Nitrogen Balance of the Mountain Meadow

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Journal of Life Sciences 2014年第10期8卷 828-834页

作者： Piotr Kacorzyk Miroslaw kasperczyk Wojciech Szewczyk Department of Grassland Management Institute of Plant Production University of Agriculture in Krakow Al. Mickiewicza 21Krakow 31-120 Poland

Synthesis of a new hydroxy functionalized polyesters by ROP copolymerization of cyclic comonomers, based on the renewable resources

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Synthesis of a new hydroxy functionalized polyesters by ROP ...