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Complementary roles of glial cells in generating region-specific neuroinflammatory responses and phagocytosis in Parkinson’s disease

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Neural Regeneration Research 2025年第10期20卷 2917-2918页

作者： Leyre Ayerra Maria S.Aymerich Universidad de Navarra Facultad de CienciasDepartamento de Bioquímica y GenéticaPamplonaSpain CIMA-Universidad de Navarra PamplonaSpain IdiSNA Instituto de Investigación Sanitaria de NavarraPamplonaSpain

Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic *** has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be *** leukocyte antigen.

关键词： inflammation leukocyte generating

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)

New approaches to identification and characterization of tioconazole in raw material and in pharmaceutical dosage forms

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Journal of Pharmaceutical Analysis 2019年第1期9卷 40-48页

作者： Natalia L.Calvo Vera A.Alvarez María C.Lamas Darío Leonardi Instituto de Química Rosario (IQUIR CONICET-UNR) área Análisis de Medicamentos Facultad de Ciencias Bioquímicas y Farmacéuticas Universidad Nacional de Rosario Grupo de Materiales Compuestos Termoplásticos (CoMP) Instituto de Investigaciones de Cienciay Tecnología de Materiales (INTEMA CONICET-UNMdP) área Técnica farmacéutica Facultad de Ciencias Bioquímicas y Farmacéuticas Universidad Nacional de Rosario

Tioconazole(TCZ), a broad-spectrum antifungal agent, has significant activity against Candida albicans and other Candida species, and therefore, it is indicated for the topical treatment of superficial *** main goal of this work is to report an exhaustive identification and characterization procedure to improve and facilitate the online quality control and continuous process monitoring of TCZ in bulk material and loaded in two different dosage forms: ovules and nail lacquer. The methodologies were based on thermal(differential scanning calorimetry(DSC), melting point, and thermogravimetry(TG)),spectroscopic(ultraviolet(UV), Raman, near infrared(NIR), infrared spectroscopy coupled to attenuated total reflectance(FTIR-ATR), and nuclear magnetic resonance(NMR)), microscopic and X-ray diffraction(XRD). The TCZ bulk powder showed a high crystallinity, as observed by XRD, with a particles size distribution(3–95 mm) resolved by microscopic measurements. TCZ melting point(82.8 °C) and a degradation peak centered at 297.8 °C were obtained by DSC and DTG, respectively. An unambiguous structure elucidation of TCZ was obtained by mono-and two-dimensional1 H and13 C NMR spectral data analysis. The FTIR-ATR, Raman and NIR spectra of both the raw material and the commercial products were analyzed and their characteristic bands were tabulated. The best methods for TCZ identification in ovules were DSC, TG, XRD, NIR and Raman, while NIR and FTIR-ATR were the most appropriate techniques to analyze it in the nail lacquer. DSC, TG, DRX, Raman, FTIR-ATR and NIR spectroscopy are effective techniques to be used in online process analysis, because they do not require sample preparation, and they are considerably sensitive to analyze complex samples.

关键词： Tioconazole Identification Characterization Pharmaceutical dosage forms Spectroscopic methods

Hepatic drug transporters and nuclear receptors:Regulation by therapeutic agents

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World Journal of Gastroenterology 2008年第46期14卷 7068-7074页

作者： Aldo D Mottino Viviana A Catania Instituto de Fisiología Experimental Facultad de Ciencias Bioquímicas y FarmacéuticasUniversidad Nacional de RosarioSuipacha 570(S2002LRL)-RosarioArgentina

The canalicular membrane represents the excretory pole of *** is an important route of elimination of potentially toxic endo-and xenobiotics(including drugs and toxins),mediated by the major canalicular transporters:multidrug resistance protein 1(MDR1, ABCB1),also known as P-glycoprotein,multidrug resistance-associated protein 2(MRP2,ABCC2),and the breast cancer resistance protein(BCRP,ABCG2).Their activities depend on regulation of expression and proper localization at the canalicular membrane,as regulated by transcriptional and post-transcriptional events,*** transcriptional level,specific nuclear receptors(NR)s modulated by ligands,co-activators and co-repressors,mediate the physiological requirements of these *** complex system is also responsible for alterations occurring in specific liver *** briefly describe the major ClassⅡNRs, pregnane X receptor(PXR)and constitutive androstane receptor(CAR),and their role in regulating expression of multidrug resistance *** therapeutic agents regulate the expression of relevant drug transporters through activation/inactivation of these *** provide some representative examples of the action of therapeutic agents modulating liver drug transporters, which in addition,involve CAR or PXR as mediators.

关键词： Drug transport Biliary secretion ABC proteins Multidrug resistance proteins Nuclear receptors Constitutive androstane receptor Pregnane X receptor Therapeutic agents

Aquaporins:Their role in cholestatic liver disease

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World Journal of Gastroenterology 2008年第46期14卷 7059-7067页

作者： Guillermo L Lehmann Maria C Larocca Leandro R Soria Raúl A Marinelli Instituto de Fisiología Experimental Consejo Nacional de Investigaciones Científicas y TécnicasFacultad de Ciencias Bioquímicas y FarmacéuticasUniversidad Nacional de Rosario2000 RosarioSanta FeArgentina

This review focuses on current knowledge on hepato-cyte aquaporins(AQPs)and their significance in bile formation and *** bile secretion results from a combined interaction of several solute transporters and AQP water channels that facilitate water flow in response to the osmotic gradients created. During choleresis,hepatocytes rapidly increase their canalicular membrane water permeability by modulating the abundance of *** question was raised as to whether the opposite process,i.e.a decreased canalicular AQP8 expression would contribute to the development of *** in several experimental models of cholestasis,such as extrahepatic obstructive cholestasis,estrogen-induced cholestasis, and sepsis-induced cholestasis demonstrated that the protein expression of hepatocyte AQP8 was impaired. In addition,biophysical studies in canalicular plasma membranes revealed decreased water permeability associated with AQP8 protein *** combined alteration in hepatocyte solute transporters and AQP8 would hamper the efficient coupling of osmotic gradients and canalicular water *** cholestasis may result from a mutual occurrence of impaired solute transport and decreased water permeability.

关键词： Aquaporin Cholestasis Estrogen Hepatocyte Obstructive cholestasis, Sepsis Water transport

Reassessing the AMPK-MTORC1 balance in autophagy in the central nervous system

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Neural Regeneration Research 2025年第11期20卷 3209-3210页

作者： Marta García-Juan Mario Villa Irene Benito-Cuesta Lara Ordónez-Gutiérrez Francisco Wandosell Centro de Biología Molecular“Severo Ochoa”(CSIC-UAM) Nicolas Cabrera 1Universidad Autónoma de MadridMadridSpain Fisiología Animal Departamento de BiologíaFacultad de CienciasUniversidad Autónoma de MadridMadridSpain department of Clinical Neuroscience CMM Karolinska Universitetssjukhuset SolnaStockholmSweden departamento de bioquímica y Biología Molecular Universidad Complutense de MadridMadridSpain Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas(CIBERNED) MadridSpain

Autophagy is a cellular degradation and recycling system,indispensable for cellular and organ development,homeostasis,and *** cellular process is evolutionarily highly conserved to quality control of many proteins and dysfunctional organelles,which finally recycle components as amino *** process is effective during normal physiology as part of anabolism and plays an additional important role during starvation(Dikic and Elazar,2018).Different types of autophagy have been chara cterized based on their dynamic,mechanism of action,target substrates,and protein *** of them are macroautophagy(hereafter called"autophagy"),microa utophagy,and chape rone-media ted autophagy(Fleming et al.,2022).

关键词： homeostasis system hereafter

Performance of cold-preserved rat liver Microorgans as the biological component of a simplified prototype model of bioartificial liver

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World Journal of Hepatology 2016年第33期8卷 1442-1451页

作者： María Dolores Pizarro María Gabriela Mediavilla Alejandra Beatriz Quintana ángel Luis Scandizzi Joaquín Valentín Rodriguez María Eugenia Mamprin Centro Binacional de Criobiología Clínica y Aplicada Instituto de Biología Molecular y Celular de Rosario Consejo Nacional de Investigaciones Científicas y Técnicas Morfología Facultad de Ciencias Bioquímicas y Farmacéuticas área Farma-cología Facultad de Ciencias Bioquímicas y FarmacéuticasUniversidad Nacional de Rosario

AIMTo develop a simplified bioartificial liver (BAL) device prototype, suitable to use freshly and preserved liver Microorgans (LMOs) as biological component. METHODSThe system consists of 140 capillary fibers through which goat blood is pumped. The evolution of hematocrit, plasma and extra-fiber fluid osmolality was evaluated without any biological component, to characterize the prototype. LMOs were cut and cold stored 48 h in BG35 and ViaSpan® solutions. Fresh LMOs were used as controls. After preservation, LMOs were loaded into the BAL and an ammonia overload was added. To assess LMOs viability and functionality, samples were taken to determine lactate dehydrogenase (LDH) release and ammonia detoxification capacity. RESULTSThe concentrations of ammonia and glucose, and the fluids osmolalities were matched after the first hour of perfusion, showing a proper exchange between blood and the biological compartment in the minibioreactor. After 120 min of perfusion, LMOs cold preserved in BG35 and ViaSpan® were able to detoxify 52.9% ± 6.5% and 53.6% ± 6.0%, respectively, of the initial ammonia overload. No significant differences were found with Controls (49.3% ± 8.8%, P ® cold preserved LMOs, respectively (n = 6, P CONCLUSIONThis prototype relied on a simple design and excellent performance. It’s a practical tool to evaluate the detoxification ability of LMOs subjected to different preservation protocols.

关键词： Rat liver Microorgans Cold preservation BG35 preservation solution Bioartificial liver device Acute liver failure

Dynamic localization of hepatocellular transporters in health and disease

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World Journal of Gastroenterology 2008年第44期14卷 6786-6801页

作者： Marcelo G Roma Fernando A Crocenzi Aldo D Mottino Instituto de Fisiología Experimental (IFISE)-facultad de ciencias bioquímicasy farmacéuticas (CONICET-U.N.R.) S2002LRLRosarioArgentina

Vesicle-based traffi cking of hepatocellular transporters involves delivery of the newly-synthesized carriers from the rough endoplasmic reticulum to either the plasma membrane domain or to an endosomal,submembrane compartment,followed by exocytic targeting to the plasma membrane. Once delivered to the plasma membrane,the transporters usually undergo recycling between the plasma membrane and the endosomal compartment,which usually serves as a reservoir of pre-existing transporters available on demand. The balance between exocytic targeting and endocytic internalization from/to this recycling compartment is therefore a chief determinant of the overall capability of the liver epithelium to secrete bile and to detoxify endo and xenobiotics. Hence,it is a highly regulated process. Impaired regulation of this balance may lead to abnormal localization of these transporters,which results in bile secretory failure due to endocytic internalization of key transporters involved in bile formation. This occurs in several experimental models of hepatocellular cholestasis,and in most human cholestatic liver diseases. This review describes the molecular bases involved in the biology of the dynamic localization of hepatocellular transporters and its regulation,with a focus on the involvement of signaling pathways in this process. Their alterations in different experimental models of cholestasis and in human cholestatic liver disease are reviewed. In addition,the causes explaining the pathological condition (e.g. disorganization of actin or actin-transporter linkers) and the mediators involved (e.g. activation of cholestatic signaling transduction pathways) are also discussed. Finally,several experimental therapeutic approaches based upon the administration of compounds known to stimulate exocytic insertion of canalicular transporters (e.g. cAMP,tauroursodeoxycholate) are described.

关键词： Hepatocellular transporters Cholestasis cAMP Bile salts Vesicular trafficking Endocytosis Signaling pathways

Renal elimination of organic anions in cholestasis

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World Journal of Gastroenterology 2008年第43期14卷 6616-6621页

作者： Adriana Mónica Torres facultad de ciencias bioquimicas y farmacéuticas Universidad Nacional de RosarioCONICETSuipacha 5312000RosarioArgentina

The disposition of most drugs is highly dependent on specialized transporters. OAT1 and OAT3 are two organic anion transporters expressed in the basolateral membrane of renal proximal tubule cells, identified as contributors to xenobiotic and endogenous organic anion secretion. It is well known that cholestasis may cause renal damage. Impairment of kidney function produces modifications in the renal elimination of drugs. Recent studies have demonstrated that the renal abundance of OAT1 and OAT3 plays an important role in the renal elimination of organic anions in the presence of extrahepatic cholestasis. Time elapsed after obstructive cholestasis has an important impact on the regulation of both types of organic anion transporters. The renal expression of OAT1 and OAT3 should be taken into account in order to improve pharmacotherapeutic efficacy and to prevent drug toxicity during the onset of this hepatic disease.

关键词： Organic anions P-aminohippurate Furosemide OAT1 OAT3 Extrahepatic cholestasis