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Alpha-1 antitrypsin deficiency and Pi*Z allele as important co-factors in the development of liver fibrosis

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World Journal of Hepatology 2024年第8期16卷 1099-1110页

作者： ana Isabel Ferreira Catarina Guimarães Vitor Macedo Silva Sofia Xavier Joana Magalhães JoséCotter Department of Gastroenterology Hospital da Senhora da Oliveira-GuimarãesGuimarães 4835-044Portugal Life and Health Sciences Research Institute School of MedicineUniversity of MinhoBraga 4710-057Portugal Life and Health Sciences Research Institute/3B’s PT Government Associate LaboratoryBraga 4710-057Portugal Department of Pulmonology Hospital Senhora da Oliveira-GuimarãesGuimarães 4835-044Portugal

BACKGROUND Alpha-1 antitrypsin deficiency(AATD)is a codominant autosomal hereditary condition that predisposes patients to the development of lung and/or liver disease,and Pi*Z allele is the most clinically relevant *** To evaluate the impact of clinical parameters and AATD phenotypes,particularly the Pi*Z allele,in liver *** Cross-sectional cohort study including consecutive patients with AATD followed in Pulmonology or Hepatology *** Included 69 patients,49.3%had Pi*MZ phenotype and 10.1%Pi**** age≥55 years,age at diagnosis≥41 years and AAT at diagnosis<77 mg/dL predicted a nonalcoholic fatty liver disease fibrosis score(NFS)not excluding advanced fibrosis[area under the curve(AUC)=0.840,P<0.001;AUC=0.836,P<0.001;AUC=0.681,P=0.025].An age≥50 years and age at diagnosis≥41 years predicted a fibrosis-4 index of moderate to advanced fibrosis(AUC=0.831,P<0.001;AUC=0.795,P<0.001).Patients with hypertension,type 2 diabetes mellitus(DM),dyslipidaemia,metabolic syndrome,and regular alcohol consumption were more likely to have a NFS not excluding advanced fibrosis(P<0.001,P=0.002,P=0.008,P<0.001,P=0.033).Patients with at least one Pi*Z allele and type 2 DM were 8 times more likely to have liver stiffness measurement≥7.1 kPa(P=0.040).CONCLUSION Risk factors for liver disease in AATD included an age≥50 years,age at diagnosis≥41 years,metabolic risk factors,regular alcohol consumption,at least one Pi*Z allele,and AAT value at diagnosis<77 mg/*** created an algorithm for liver disease screening in AATD patients to use in primary care,selecting those to be referred to Hepatology consultation.

关键词： Alpha-1 antitrypsin deficiency Liver fibrosis Nonalcoholic fatty liver disease fibrosis score Fibrosis-4 index Liver stiffness measurement

Periodontal disease:A silent factor in the development and progression of diabetic retinopathy

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World Journal of Diabetes 2024年第8期15卷 1672-1676页

作者： Sarah Monserrat LomelíMartínez Irán Cortés Trujillo Melissa Martínez Nieto ana Esther Mercado González Department of Medical and Life Sciences Centro Universitario de la CiénegaUniversidad de GuadalajaraOcotlán 47810Mexico Master of Public Health Department of Wellbeing and SustainableCentro Universitario del NorteUniversidad de GuadalajaraColotlán 46200Mexico Periodontics Program Department of Integrated Dentistry ClinicsCentro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajara 44340Mexico Antiguo Hospital Civil de Guadalajara“Fray Antonio Alcalde” Guadalajara 44280Mexico

The global increase in the prevalence of type 2 diabetes mellitus(T2DM)and its complications presents significant challenges to public ***,periodontal disease(PD)was recognized as a factor that is likely to influence the progression of T2DM and its complications due to its potential to exacerbate systemic inflammation and oxidative *** this editorial,we comment on the article published by Thazhe Poyil et al in the very recent issue of the World Journal of Diabetes in 2024,which investigated the correlation between PD and diabetic retinopathy(DR)in T2DM patients,with emphasis on the association between periodontal swollen surface area,glycated hemoglobin(HbA1c),interleukin-6(IL-6),and lipoprotein(a).The findings by Thazhe Poyil et al are significant as they demonstrate a strong link between PD and DR in T2DM *** correlation highlights the importance of addressing periodontal health in diabetes management to potentially reduce the risk and severity of DR,a complication of *** integration of periodontal evaluation and treatment into diabetes care protocols may lead to improved glycemic control and better overall outcomes for T2DM patients.A few studies have established an interconnection between PD and diabetic complication,specifically DR,in T2DM patients,which we aim to highlight in this *** was placed on the different mechanisms that suggest a bidirectional relationship between PD and T2DM,where the presence of periodontal inflammation negatively influenced glycemic control and contributed to the development and progression of DR through shared inflammatory and vascular *** article highlights the importance of collaboration amongst diabetes specialists,ophthalmologists,periodontists,and public health professionals to advance the prevention,early detection,and treatment of PD and *** will improve the health and quality of life of T2DM ***,the editorial highlights the need for further re

关键词： Type 2 diabetes mellitus Periodontal disease Periodontitis Diabetic retinopathy Editorial

Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

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Neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： Ramón Pérez-Núñez María Fernanda González ana María Avalos Lisette Leyton Cellular Communication Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDiS) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant type of glial cell in the central nervous *** injury and inflammation,astrocytes become reactive and undergo morphological and functional *** on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,***,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and *** analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their *** actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune *** phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo *** astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory ***,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their *** highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT *** targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial *** dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function *** review emphasizes the importance of employing astrocyte-exclusive models to underst

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)

Outcomes of long-acting injectable antipsychotics use in pregnancy:A literature review

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World Journal of Psychiatry 2024年第4期14卷 582-599页

作者： ana V Pejčić Srdjan M Stefanović MilošN Milosavljević Vladimir S Janjić Marko M Folić Nevena D Folić Jovana Z Milosavljević Department of Pharmacology and Toxicology Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia Department of Pharmacy Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia Department of Clinical Pharmacology University Clinical Center KragujevacKragujevac 34000Serbia Department of Psychiatry Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia Clinic for Psychiatry University Clinical Center KragujevacKragujevac 34000Serbia Center for Pharmaceutical and Pharmacological Research Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia Department of Pediatrics Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia Pediatric Clinic University Clinical Center KragujevacKragujevac 34000Serbia Department of anatomy Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia

BACKGROUND Women with a history of serious psychotic disorders are at increased risk of disease relapse during ***-acting injectable(LAI)antipsychotics have been widely used to improve adherence and prevent relapse in patients with various severe psychotic disorders,but there is a lack of high-quality data from previous research on the safety of LAI antipsychotics during *** To summarize relevant data on maternal,pregnancy,neonatal,and developmental outcomes from published cases of LAI antipsychotic use in *** A literature search was performed through November 11,2023,using three online databases:PubMed/MEDLINE,Scopus,and Web of *** reports or case series that reported information about the outcomes of pregnancy in women who used LAI antipsychotics at any point in pregnancy,with available full texts,were *** statistics,narrative summation,and tabulation of the extracted data were *** A total of 19 publications satisfied the inclusion criteria:3 case series,15 case reports,and 1 conference *** reported the outcomes of LAI antipsychotic use in 74 women and 77 *** use of secondgeneration LAI antipsychotics was reported in the majority(n=47;61.0%)of ***-generation LAI antipsychotics were administered during 30 pregnancies(39.0%).Most of the women(approximately 64%)had either satisfactory control of symptoms or no information about relapse,while approximately 12%of them had developed gestational diabetes mellitus.A minority of cases reported adverse outcomes such as stillbirth,spontaneous abortion,preterm birth,low birth weight,congenital anomalies,and neurological manifestations in ***,there were no reports of negative long-term developmental *** Currently available data seem reassuring,but further well-designed studies are required to properly evaluate the risks and benefits of LAI antipsychotic use during pregnancy.

关键词： Antipsychotic agents Long-acting injectable Pregnancy Outcome Review

Robotic Surgery: An Effective Treatment Option for Epiphrenic Diverticulum Associated with Nutcracker Esophagus

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Surgical Science 2024年第1期15卷 1-6页

作者： Augusto Tinoco Gilberto Carvalho Leonardo Tinoco ana Paula Quintão Department of Digestive Surgery Hospital S&#227o Jos&#233 do Ava&#237 Itaperuna Brazil

Background: Epiphrenic Diverticulum is frequently associated with esophageal motility disorders, such as nutcrackers esophagus. The diagnosis is usually made using imaging studies such as a Barium esophagogram, and esophageal manometry. Surgical treatment options for epiphrenic diverticulum and EN include diverticulectomy and wide myotomy. Aim: The resection of three epiphrenic diverticula and extensive myotomy were performed by robotic thoracoscopy uneventfully. Case presentation: A 65-year-old female complaining of dysphagia for solid foods, Chest pain and regurgitation. Esophagogastroduodenoscopy (EDG) with difficulty in advancing the endoscope at 25 cm and demonstrating an ED, no hiatal hernia and normal stomach and duodenum. Barium Esophagogram showed multiple diverticula and tortuosity throughout the esophagus. Conclusion: With robotic surgery, surgeons can perform highly precise operations with enhanced 3D vision and control. Through this cutting-edge approach, the treatment of ED associated with EN can be drastically changed, promising better outcomes for patients.

关键词： Robotic Surgery Myotomy Nutcracker Esophagus Epiphrenic Diverticulum

Is magnesium deficiency the major cause of needle chlorosis of Pinus taeda in Brazil?

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Journal of Forestry Research 2024年第2期35卷 209-221页

作者： Antônio Carlos Vargas Motta Shizuo Maeda Valdécio dos Santos dos Santos Rodrigues Tamires Maiara Ercole Stephen Arthur Prior ana Elisa Lyra Brumat Amanda Pacheco Cardoso Moura Julierme Zimmer Barbosa João Bosco Vasconcellos Gomes Department of Soil Sciences and Agriculture Engineering Federal University of ParanáR.dos Funcionários1540.CuritibaParanáCEP 80035‑050Brazil Brazilian Agricultural Research Company Embrapa FlorestasEstr.da Ribeira–Br‑476Km 111–Parque Monte Castelo.ColomboParanáCEP 83411‑000Brazil United States Department of Agriculture‑Agricultural Research Service USDA-ARS National Soil Dynamics Laboratory411 South Donahue DriveAuburnAL 36832USA Reforestation Remasa Rodovia PR 170–Km 522.BiturunaParanáCEP 84640‑000Brazil Federal Institute of Southeast of Minas Gerais R.Luz Interior360.Juiz de ForaMinas Gerais CEP 36030‑713Brazil

Needle chlorosis(NC)in Pinus taeda *** in Brazil becomes more frequent after second and third harvest rotation *** a study to identify factors contributing to yellowing needle chorosis(YNC),trees were grown in soils originating from contrasting parent materials,and soils and needles(whole,green and chlorotic portions)from 1-and 2-year-old branches and the first and second needle flush release at four sites with YNC on *** were analyzed for various elements and *** soils had very low base levels(Ca^(2+),Mg^(2+)and K^(+))and P,suggesting a possible lack of multiple *** symptoms started at needle tips,then extended toward the needle base with *** flush needles had longer portions with YNC than second flush needles *** from the lower crown also had more symptoms along their length than those higher in the *** were similar to those reported for *** chlorotic portions,Mg and Ca concentrations were well below critical values;in particular,Mg levels were only one third of the critical value of 0.3 g kg^(-1).Collectively,results suggest that Mg deficiency is the primary reason for NC of *** in various parent soils in Brazil.

关键词： Nutritional deficiency Forest management Soil depletion Pine foliar analysis Needle chlorosis

Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery-design,characterization,and biological insights

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Nano Research 2024年第10期17卷 9111-9125页

作者： ana M.López-Estévez Y.Zhang María Medel Iker Arriaga Lucía Sanjurjo Cristian Huck-Iriart Nicola G.A.Abrescia María J.Vicent Defang Ouyang Dolores Torres María José Alonso Center for Research in Molecular Medicine and Chronic Diseases(CiMUS) University of Santiago de CompostelaSantiago de Compostela 15782Spain Department of Pharmacology Pharmacy and Pharmaceutical TechnologySchool of PharmacyUniversity of Santiago de CompostelaSantiago de Compostela 15782Spain Health Research Institute of Santiago de Compostela(IDIS) Santiago de Compostela 15782Spain State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences(ICMS)University of MacaoMacao 999078China Polymer Therapeutics Laboratory and CIBERONC Prince Felipe Research Centre Valencia E-46012Spain Structure and Cell Biology of Viruses Lab CIC bioGUNEBasque Research and Technology Alliance(BRTA)Derio 48160Spain ALBA Synchrotron Light Source Experiments DivisionCerdanyola del VallèsBarcelona 08290Spain IKERBASQUE Basque Foundation for ScienceBilbao 48009Spain

The current spotlight of cancer therapeutics is shifting towards personalized medicine with the widespread use of monoclonal antibodies(mAbs).Despite their increasing potential,mAbs have an intrinsic limitation related to their inability to cross cell membranes and reach intracellular *** offers promising solutions to overcome this limitation,however,formulation challenges *** challenges are the limited loading capacity(often insufficient to achieve clinical dosing),the complex formulation methods,and the insufficient characterization of mAb-loaded ***,we present a new nanocarrier consisting of hyaluronic acid-based nanoassemblies(Hanas)specifically designed to entrap mAbs with a high efficiency and an outstanding loading capacity(50%,w/w).Hanas composed by an mAb,modified HA and phosphatidylcholine(PC)resulted in sizes of~100 nm and neutral surface *** modeling identified the principal factors governing the high affinity of mAbs with the amphiphilic HA and *** composition and structural configuration were analyzed using the orthogonal techniques cryogenic transmission electron microscopy(cryo-TEM),asymmetrical flow field-flow fractionation(AF4),and small-angle X-ray scattering(SAXS).These techniques provided evidence of the formation of core-shell nanostructures comprising an aqueous core surrounded by a bilayer consisting of phospholipids and amphiphilic *** vitro experiments in cancer cell lines and macrophages confirmed Hanas’low toxicity and ability to transport mAbs to the intracellular *** reproducibility of this assembling process at industrial-scale batch sizes and the long-term stability was *** conclusion,these results underscore the suitability of Hanas technology to load and deliver biologicals,which holds promise for future clinical translation.

关键词： monoclonal antibody nanoparticles hyaluronic acid characterization particle size computational modeling

Neuroprotective effects of G9a inhibition through modulation of peroxisome-proliferator activator receptor gamma-dependent pathways by miR-128

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Neural Regeneration Research 2024年第11期19卷 2532-2542页

作者： Aina Bellver-Sanchis Pedro AAvila-López Iva Tic David Valle-García Marta Ribalta-Vilella Luis Labrador Deb Ranjan Banerjee ana Guerrero Gemma Casadesus Coralie Poulard Mercè Pallàs Christian Grinán-Ferré Department of Pharmacology and Therapeutic Chemistry Institut de Neurociències-Universitat de BarcelonaBarcelonaSpain Department of Biochemistry and Molecular Genetics Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Institute of Biotechnology National Autonomous University of MexicoCuernavacaMexico Department of Pharmacology and Therapeutics Health Science Center-University of FloridaGainesvilleFLUSA Department of Chemistry National Institute of Technology DurgapurM G AvenueDurgapurWest BengalIndia Cancer Research Cancer Lyon Universitéde LyonLyonFrance Inserm U1052 Centre de Recherche en Cancérologie de LyonLyonFrance CNRS UMR5286 Centre de Recherche en Cancérlogie de LyonLyonFrance Centro de Investigación en Red Enfermedades Neurodegenerativas(CIBERNED)Instituto de Salud Carlos IIIMadridSpain Neuroimmunology Department National Institute of Neurology and Neurosurgery“Manuel Velasco Suárez”Mexico CityMexico

Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative ***,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s ***,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and *** better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor *** found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)***,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control *** also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a *** confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative *** this setting,treatment with G9a inhibitor increases both cell survival and antioxidant ***,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and *** addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers ***,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a ***,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.

关键词： aging cognitive decline epigenetics G9a inhibition microRNAs miR-128 peroxisome-proliferator activator receptorγ(PPARγ) PPARG SAMP8

基于艺术治疗方法的护理干预在边缘型人格障碍患者中的应用

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International Journal of Nursing Sciences 2024年第2期11卷 205-213页

作者： ana Morales-Alonso Angela Iglesias-de-la-Iglesia Miriam Alonso-Maza Dr.Rodríguez Lafora Hospital(Hospital Dr.Rodríguez Lafora) MadridSpain Department of Nursing and Stomatology University Rey Juan CarlosAlcorconMadridSpain

目的ZentangleR艺术治疗方法被应用于心理健康相关领域,尚未在边缘型人格障碍患者得到验证。本研究分析边缘型人格障碍患者接受ZentangleR艺术治疗方法的练习体验。方法采用现象学解释方法,对患者进行半结构化访谈。患者均已在西班牙某... 详细信息

目的ZentangleR艺术治疗方法被应用于心理健康相关领域,尚未在边缘型人格障碍患者得到验证。本研究分析边缘型人格障碍患者接受ZentangleR艺术治疗方法的练习体验。方法采用现象学解释方法,对患者进行半结构化访谈。患者均已在西班牙某医院的人格障碍治疗室接受了每个月1次,共6次ZentangleR艺术治疗。本研究中共访谈了15例患者。Smith、Flowers和Larkin方法用于资料分析中的评估。结果根据研究结果,共提炼出3个类别的主题:有耕耘即有收获(参与者报告了注意力、放松、人际关系、与环境互动方面的改善,以及接受和改变的积极体验);众擎易举(患者认可在团体中感觉更好,并建立了相互联系;他们也描述了团体环境对个人行为的影响);画出自己的轨迹(通过绘画方式提供了自我表达和自我认识的媒介,通过情感表达提升了幸福感,提高了创造力,增强了自信心)。结论通过练习ZentangleR,患者可以作出灵活性和适应性等行为反应,通过焦虑管理、冲动控制改善情绪健康,学习应对问题,提高自尊或注意力。心理健康护理在边缘型人格的综合治疗及协同多样化补充性干预措施中发挥着积极作用。

关键词：艺术治疗边缘型人格障碍心理健康护理 Zentangle®