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8-Hydroxyquinolylnitrones as multifunctional ligands for the therapy of neurodegenerative diseases

Acta Pharmaceutica Sinica B 2023年第5期13卷 2152-2175页

作者： Damijan Knez Daniel Diez-Iriepa Mourad Chioua Andrea Gottinger Milica Denic Fabien Chantegreil Florian Nachon Xavier Brazzolotto Anna Skrzypczak-Wiercioch Ane Meden Anja Pilar Janko Kos Simon akelj Jure Stojan kinga saat Julia Serrano Ana Patricia Fernández Aitana Sánchez-García Ricardo Martínez-Murillo Claudia Binda Francisco López-Muoz Stanislav Gobec JoséMarco-Contelles University of Ljubljana Faculty of PharmacyLjubljana 1000Slovenia Laboratory of Medicinal Chemistry(Institute of Organic Chemistry CSIC)Madrid 28006Spain Departamento de Química Orgánicay Química Inorgánica Alcaláde HenaresMadrid 28871Spain Department of Biology and Biotechnology University of PaviaPavia 27100Italy Département de Toxicologie et Risques Chimiques Institut de Recherche Biomédicale des ArméesParis 91220France Department of Animal Anatomy and Preclinical Sciences University Centre of Veterinary Medicine JU-UAUniversity of Agriculture in KrakowKrakow 30-059Poland Institute of Biochemistry Faculty of MedicineUniversity of LjubljanaLjubljana 1000Slovenia Department of Pharmacodynamics Chair of PharmacodynamicsFaculty of PharmacyJagiellonian University Medical CollegeKrakow 30-688Poland Department of Translational Neurobiology Neurovascular Research GroupCajal Institute(CSIC)Madrid 28002Spain Biotechnology and Vegetal Biology Department Escuela Técnica Superior de Ingeniería AgronómicaAlimentaria y de BiosistemasUniversidad Politécnica de MadridMadrid 28040Spain Faculty of Health Camilo JoséCela University of Madrid(UCJC)Neuropsychopharmacology Unit“Hospital 12 de Octubre”Research InstituteMadrid 28692Spain

We describe the development of quinolylnitrones(QNs)as multifunctional ligands inhibiting cholinesterases(ChEs:acetylcholinesterase and butyrylcholinesterase—h BChE)and monoamine oxidases(hMAO-A/B)for the therapy of neurodegenerative diseases.We identified QN 19,a simple,low molecular weight nitrone,that is readily synthesized from commercially available 8-hydroxyquinoline-2-carbaldehyde.Quinolylnitrone 19 has no typical pharmacophoric element to suggest ChE or MAO inhibition,yet unexpectedly showed potent inhibition of h BChE(IC50=1.06±0.31 nmol/L)and h MAO-B(IC_(50)=4.46±0.18μmol/L).The crystal structures of 19 with hBChE and hMAO-B provided the structural basis for potent binding,which was further studied by enzyme kinetics.Compound 19 acted as a free radical scavenger and biometal chelator,crossed the blood—brain barrier,was not cytotoxic,and showed neuroprotective properties in a 6-hydroxydopamine cell model of Parkinson's disease.In addition,in vivo studies showed the anti-amnesic effect of 19 in the scopolamine-induced mouse model of AD without adverse effects on motoric function and coordination.Importantly,chronic treatment of double transgenic APPswe-PS1δE9 mice with 19 reduced amyloid plaque load in the hippocampus and cortex of female mice,underscoring the disease-modifying effect of QN 19.

关键词： Quinolylnitrone Butyrylcholinesterase Monoamine oxidase B Alzheimer's disease Multifunctional ligands 6-Hydroxydopamine model Passive avoidance task Novel object recognition

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栖息地条件对白杨与枫树林群落中高山天南星的丰富度和选定个体特征的影响

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Journal of Plant Ecology 2024年第1期17卷 33-49页

作者： Tomasz Wójcik kinga Kostrakiewicz-Gierałt Department of Nature Conservation and Landscape Ecology Institute of Agricultural SciencesLand Management and Environmental ProtectionUniversity of Rzeszow35-601 RzeszowPoland Department of Tourism Geography and Ecology Institute of TourismFaculty of Tourism and RecreationUniversity of Physical Education in Krakow31-571 KrakowPoland

本研究于2020至2021年在西喀尔巴阡山脉的山麓地区进行,研究了高山天南星(Arum alpinum)的物种数量和选定特征的空间-时间变异。调查分别在4个永久样地中进行(Patch Ⅰ、Ⅱ、Ⅲ、Ⅳ)。Patch Ⅰ和Patch Ⅲ位于以低矮植被为主的枫树-鹅耳... 详细信息

本研究于2020至2021年在西喀尔巴阡山脉的山麓地区进行,研究了高山天南星(Arum alpinum)的物种数量和选定特征的空间-时间变异。调查分别在4个永久样地中进行(Patch Ⅰ、Ⅱ、Ⅲ、Ⅳ)。Patch Ⅰ和Patch Ⅲ位于以低矮植被为主的枫树-鹅耳枥林(Tilio cordatae-Carpinetum betuli)林地中,而Patch Ⅱ和Patch Ⅳ位于以阔叶物种为主的白杨(Populetum albae)河滩林中。调查结果表明,高山天南星最丰富种群出现在Patch Ⅰ,但Patch Ⅱ和Patch Ⅳ中也存在大量的营养体和繁殖个体。个体性状的时间变异性在Patch Ⅳ最低,其次是Patch Ⅰ和Patch Ⅱ,在Patch Ⅲ最高。所有种群中均发现叶柄长度与叶片尺寸以及有性茎长度与果序特征之间的关系显著呈正相关,这一发现证实了先前的研究。这些研究结果表明,高山天南星与特定的森林群落没有密切关联。充足的遮荫和湿润富养分的土壤对该物种有利,而干燥的土壤和过多的日照可能会限制其个体的开花与结果。

关键词：高山天南星(Arum alpinum) 枫树-鹅耳枥林河滩林开花茎果序叶片山地物种

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Influence of processing history on microstructure， mechanical properties， and electrical conductivity of Cu-0.7Mg alloy

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Transactions of Nonferrous Metals Society of China 2024年

作者： Alireza KALHOR kinga RODAK Marek TKOCZ Bartosz CHMIELA Ivo SCHINDLER ?ukasz POLOCZEK Krzysztof RADWA?SKI Hamed MIRZADEH Marian KAMPIK Faculty of Materials Engineering Silesian University of Technology V?B – Technical University of Ostrava Faculty of Materials Science and Technology Materials Research Group ?ukasiewicz Upper Silesian Institute of Technology School of Metallurgy and Materials Engineering College of Engineering University of Tehran Faculty of Electrical Engineering Silesian University of Technology

The effects of forward extrusion as well as extrusion combined with reversible torsion (KoBo extrusion)， followed by additional deformation via the MaxStrain module of the Gleeble thermomechanical simulator， on the microstructure， mechanical properties， and electrical conductivity of a Cu-0.7Mg (wt.%) alloy， were investigated in this work. The simulation results highlighted the critical influence of processing history in determining the equivalent strain distribution. The sample subjected to forward extrusion at 400 ℃and subsequent MaxStrain processing (FM sample)， possessed 76% lower grain size compared to the sample processed solely with MaxStrain (AM sample). Likewise， the KoBo-extruded and MaxStrain-processed sample (KM sample) exhibited 66% smaller grain size compared to the AM sample. Tensile test results revealed that the AM， FM， and KM samples， respectively， possessed 251%， 288%， and 360% higher yield strength， and 95%， 121%， and 169% higher tensile strength compared to the initial annealed alloy， as a result of grain refinement as well as deformation strengthening. Finally， the electrical conductivity measurements revealed that AM， FM， and KM samples， respectively， possessed electrical conductivity values of 37.9， 35.6， and 32.0 (MS/m)， which， considering their mechanical properties， makes them eligible to be categorized as high-strength and high-conductivity copper alloys.

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The influence of Mycoplasma species on human and canine semen quality:a review

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Asian Journal of Andrology 2023年第1期25卷 29-37页

作者： kinga Domrazek Ilona Kaszak Szymon Kanafa Mariusz Sacharczuk Piotr Jurka Laboratory of Small Animal Reproduction Institute of Veterinary MedicineWarsaw University of Life SciencesNowoursynowska 159C StreetWarsaw 02-787Poland Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences Jastrz biec Postepu Street 36AMagdalenka 05-552Poland

Mycoplasma species(spp.)are bacteria that are difficult to detect.Currently,the polymerase chain reaction(PCR)is considered the most effective diagnostic tool to detect these microorganisms in both human and veterinary medicine.There are 13 known species of human Mycoplasma and 15 species of canine Mycoplasma.Owing to the difficulties in identifying the individual species of Mycoplasma,there is a lack of information regarding which species are saprophytic and which are pathogenic.The prevalence of the individual species is also unknown.In addition,in both humans and dogs,the results of some studies on the impact of Mycoplasma are conflicting.The presence of Mycoplasma spp.on the epithelium of reproductive tract is often associated with infertility,although they are also detected in healthy individuals.The occurrence of Mycoplasma spp.is more common in dogs(even 89%)than in humans(1.3%–4%).This is probably because the pH of a dog's genital is more conducive to the growth of Mycoplasma spp.than that of humans.Phylogenetically,human and canine Mycoplasma are related,and majority of them belong to the same taxonomic group.Furthermore,40%of canine Mycoplasma spp.are placed in common clusters with those of human.This suggests that species from the same cluster can play a similar role in the canine and human reproductive tracts.This review summarizes the current state of knowledge about the impact of Mycoplasma on canine and human male fertility as well as the prospects of further development in this field.

关键词： Mycoplasma sperm morphology sperm motility

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Protocadherin gamma C3:a new player in regulating vascular barrier function

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Neural Regeneration Research 2023年第1期18卷 68-73页

作者： Victoria Kaupp kinga G.Blecharz-Lang Christina Dilling Patrick Meybohm Malgorzata Burek Department of Anesthesiology Intensive CareEmergency and Pain MedicineUniversity of WürzburgUniversity Hospital WürzburgWürzburgGermany Department of Experimental Neurosurgery Charité-UniversitätsmedizinBerlinGermany

Defects in the endothelial cell barrier accompany diverse malfunctions of the central nervous system such as neurodegenerative diseases,stroke,traumatic brain injury,and systemic diseases such as sepsis,viral and bacterial infections,and cancer.Compromised endothelial sealing leads to leaking blood vessels,followed by vasogenic edema.Brain edema as the most common complication caused by stroke and traumatic brain injury is the leading cause of death.Brain microvascular endothelial cells,together with astrocytes,pericytes,microglia,and neurons form a selective barrier,the so-called blood-brain barrier,which regulates the movement of molecules inside and outside of the brain.Mechanisms that regulate blood-brain barrier permeability in health and disease are complex and not fully understood.Several newly discovered molecules that are involved in the regulation of cellular processes in brain microvascular endothelial cells have been described in the literature in recent years.One of these molecules that are highly expressed in brain microvascular endothelial cells is protocadherin gamma C3.In this review,we discuss recent evidence that protocadherin gamma C3 is a newly identified key player involved in the regulation of vascular barrier function.

关键词： blood-brain barrier brain microvascular endothelial cells permeability protein interaction protocadherin gamma C3 protocadherins tight junctions

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Evaluation of the nutritional status of patients with liver cirrhosis

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World Journal of Hepatology 2023年第7期15卷 914-924页

作者： Barbara Janota Aneta Krupowicz kinga Noras Ewa Janczewska Department of Basic Medical Sciences Faculty of Public Health in BytomMedical University of Silesia in KatowiceBytom 41-902Poland ID Clinic Mysłowice 41-400Poland Department of Biometry Warsaw University of Life SciencesWarsaw 02-787Poland

BACKGROUND Progressive malnutrition coexists with liver diseases,particularly in patients with cirrhosis.Early diagnosis of malnutrition in patients with advanced stages of chronic liver disease and the implementation of appropriate nutritional treatment for malnourished patients should be an integral part of the therapeutic process.AIM To evaluate the nutritional status of patients with various severities of advanced liver fibrosis,using various nutritional status parameters.METHODS This study involved 118 patients with liver cirrhosis who were classified into three groups according to their Child-Pugh score.The nutritional status of the patients in each group was assessed using different methods.The average values obtained from the measurements were calculated for each research group.The influence of disease stage on the examined parameters of nutritional status was determined using one-way analysis of variance.To investigate the relationship between the parameters determining nutritional status and the stage of disease advancement,a correlation analysis was performed.RESULTS The Child-Pugh A group had the highest mean body weight(76.42 kg),highest mean body mass index(BMI)(26.72 kg/m²),and largest mean arm circumference(27.64 cm).In the Child-Pugh B group,the mean scores of all examined variables were lower than those of the Child-Pugh A group,whereas the mean body weight and BMI of the Child-Pugh C group were higher than those of the Child-Pugh B group.There was a very strong correlation between the Child-Pugh classification and subjective global assessment score;a very strong correlation between the Child-Pugh classification and arm circumference;a strong correlation between the Child-Pugh classification and body weight,albumin concentration,fat-free mass index,muscle mass index,phase angle,and BMI;and an average correlation between Child-Pugh classification and fat mass index.Notably,these indicators deteriorated with disease progression.CONCLUSION Advanced liver fibrosis leads to the deterioration of many

关键词： Liver cirrhosis Fibrosis Nutritional status Malnourishment Sarcopenia

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Applying Rational Envelope curves for skinning purposes

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Frontiers of Information Technology & Electronic Engineering 2021年第2期22卷 202-209页

作者： kinga KRUPPA Faculty of Informatics University of DebrecenDebrecen H-4028Hungary Doctoral School of Informatics University of DebrecenDebrecen H-4028Hungary

Special curves in the Minkowski space such as Minkowski Pythagorean hodograph curves play an important role in computer-aided geometric design,and their usages are thoroughly studied in recent years.Bizzarri et al.(2016)introduced the class of Rational Envelope(RE)curves,and an interpolation method for G1 Hermite data was presented,where the resulting RE curve yielded a rational boundary for the represented domain.We now propose a new application area for RE curves:skinning of a discrete set of input circles.We show that if we do not choose the Hermite data correctly for interpolation,then the resulting RE curves are not suitable for skinning.We introduce a novel approach so that the obtained envelope curves touch each circle at previously defined points of contact.Thus,we overcome those problematic scenarios in which the location of touching points would not be appropriate for skinning purposes.A significant advantage of our proposed method lies in the efficiency of trimming offsets of boundaries,which is highly beneficial in computer numerical control machining.

关键词： Medial axis transform Envelope Interpolation Skinning Circle

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Lower Extremity Arterial Disease in Patients with Type 2 Diabetes: Prevalence and Associated Factors at the Libreville University Hospital Center

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World Journal of Cardiovascular Diseases 2024年第5期14卷 295-308页

作者： Allognon Mahutondji Christian Ayo Bivigou Elsa Ntoutoume Mvé Dylan Anthony N’nang Jean-Fidel kinga Armel Mpori Jamila Myrtille Akagah Kondé Christelle Ndoume Obiang Francis Yékini Carole Fadylath Ndjibah Alakoua Cajole Ludvine Babongui Boussougou Latifah Mipinda Jean-Bruno Moubamba Franck Ecke Nzengue Jean-Emmanuel Houenassi Dèdonougbo Martin Boguikouma Jean-Bruno Department of Medicine and Medical Specialties Health Sciences University (USS) Libreville Gabon Cardiology Service Libreville University Hospital Center (CHUL) Libreville Gabon Department of Physiology Health Sciences University Libreville Gabon Amissa Bongo Regional Hospital Franceville Gabon Mother-Child Hospital Center Jeanne Ebori Foundation Libreville Gabon Medicine Service Owendo University Hospital Center Owendo Gabon

Introduction: Lower extremity arterial disease in diabetic patients has distinct characteristics. Objectives: To study the hospital frequency of lower extremity arterial disease and identify associated factors in diabetic patients at the Libreville University Hospital Center (CHUL). Materials and Methods: This was a cross-sectional study conducted from July 1, 2023, to January 31, 2024, in the endocrinology department of the CHUL. All patients with type 2 diabetes over the age of 18 admitted to this department, regardless of the reason for hospitalization, who provided informed consent, were included. Socio-demographic data and cardiovascular risk factors were recorded. Personal and family cardiovascular history and functional symptoms were investigated. The physical examination included measuring blood pressure, heart rate, and the ankle-brachial index in all patients. Results: A total of 219 patients were included, of whom 75 had lower extremity arterial disease, representing a prevalence of 34.24%. It was compensated in 28 cases (37.33%) and decompensated in 39 patients (52%). In eight cases (10.67%), there was critical chronic ischemia. Cardiovascular risk factors associated with diabetes were physical inactivity (89.5%), hypertension (55.25%), overweight (49.77%), obesity (22.84%), and smoking (10.04%). In multivariate analysis, only hypertension (OR = 2.09;95% CI: 1.05 - 4.17;p = 0.035) and LDL cholesterol (OR = 2.75;95% CI: 1.10 - 6.85;p = 0.03) were significantly associated with lower extremity arterial disease in diabetics at the University Hospital of Libreville. Conclusion: Lower extremity arterial disease is common in diabetic patients at the University Hospital of Libreville. It is often asymptomatic, thus requiring systematic screening.[-rId11-]

关键词： Lower Extremity Arterial Disease Diabetes Hypertension Ankle-Brachial Index Gabon

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Changes in the gut mycobiome in pediatric patients in relation to the clinical activity of Crohn's disease

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World Journal of Gastroenterology 2023年第14期29卷 2172-2187页

作者： Agnieszka Krawczyk Dominika Salamon kinga Kowalska-Duplaga Barbara Zapała Teofila Książek Marta Drażniuk-Warchoł Tomasz Gosiewski Department of Microbiology Division of Molecular Medical MicrobiologyJagiellonian University Medical CollegeCracow 31-121Poland Department of Pediatrics Gastroenterology and NutritionJagiellonian University Medical CollegeCracow 30-663Poland Department of Clinical Biochemistry Jagiellonian University Medical CollegeCracow 31-066Poland Department of Medical Genetics Jagiellonian University Medical CollegeCracow 30-663Poland Department of Pediatrics Gastroenterology and NutritionUniversity Children's HospitalCracow 30-663Poland

BACKGROUND Numerous studies have shown that in Crohn’s disease(CD),the gut microbiota is of great importance in the induction and maintenance of inflammation in the gastrointestinal tract.Until recently,studies have focused almost exclusively on bacteria in the gut.Lately,more attention has been paid to the role of intestinal fungi.AIM To study the gut mycobiome analysis of pediatric patients with CD(in different stages of disease activity)compared to healthy children.METHODS Fecal samples were collected from patients:With active,newly diagnosed CD(n=50);active but previously diagnosed and treated CD(n=16);non-active CD and who were in clinical remission(n=39)and from healthy volunteers(n=40).Fungal DNA was isolated from the samples.Next,next generation sequencing(MiSeq,Illumina)was performed.The composition of mycobiota was correlated with clinical and blood parameters.RESULTS Candida spp.were overrepresented in CD patients,while in the control group,the most abundant genus was Saccharomyces.In CD patients,the percentage of Malassezia was almost twice that of the control(P<0.05).In active CD patients,we documented a higher abundance of Debaryomyces hansenii(D.hansenii)compared to the non-active CD and control(P<0.05)groups.Moreover,statistically significant changes in the abundance of Mycosphaerella,Rhodotorula,and Microidium were observed.The analyses at the species level and linear discriminant analysis showed that in each group it was possible to distinguish a specific species characteristic of a given patient population.Moreover,we have documented statistically significant correlations between:D.hansenii and patient age(negative);C.zeylanoides and patient age(positive);C.dubliniensis and calprotectin(positive);C.sake and calprotectin(positive);and C.tropicalis and pediatric CD activity index(PCDAI)(positive).CONCLUSION Mycobiome changes in CD patients,and the positive correlation of some species with calprotectin or PCDAI,give strong evidence that fungi may be of key importance in the development of CD.

关键词： Intestinal mycobiome Fungi Crohn’s disease Inflammatory bowel disease Next generation sequencing Molecular microbiology

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Effect of Compression with Oscillatory Torsion Processing on Structure and Properties of Cu

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Journal of Materials Science & Technology 2011年第11期27卷 1083-1088页

作者： kinga Rodak Jacek Pawlicki Department of Materials Science Silesian University of Technology Department of Materials Technology Silesian University of Technology

The results presented in this study were concerned with microstructures and mechanical properties of poly- crystalline Cu subjected to plastic deformation by a compression with oscillatory torsion process. Different deformation parameters of the compression with oscillatory torsion process were adopted to study their effects on the microstructure and mechanical properties. The deformed microstructure was characterized quantitatively by electron backscattered diffraction （EBSD） and scanning transmission electron microscopy （STEM）. Mechanical properties were determined on an MTS QTest/10 machine equipped with digital image correlation. From the experimental results, processes performed at high compression speed and high torsion frequency are recommended for refining the grain size. The size of structure elements, such as average grain size （D） and subgrain size （d）, reached 0.42 μm and 0.30 μm, respectively, and the fraction of high angle boundaries was 35% when the sample was deformed at a torsion frequency f = 1.6 Hz and compression rate v= 0.04 mm/s. These deformation parameters led to an improvement in the strength properties. The material exhibited an ultimate tensile strength （UTS） of 434 MPa and a yield strength （YS） of 418 MPa. These values were about two times greater than those of the initial state.

关键词： Severe plastic deformation Copper Fine-grained microstructure Electronbackscattered diffraction （EBSD） Scanning transmission electronmicroscopy （STEM）

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