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Role of peripheral amyloid-β aggregates in Alzheimer’s disease: mechanistic, diagnostic, and therapeutic implications

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Neural Regeneration Research 2025年第4期20卷 1087-1089页

作者： Nazaret Gamez rodrigo morales Department of Neurology The University of Texas Health Science Center at HoustonHoustonTXUSA Centro Integrativo de Biologia y Quimica Aplicada(CIBQA) Universidad Bernardo O’HigginsSantiagoChile

Compelling evidence demonstrates that the levels of peripheral amyloid-β(Aβ)fluctuate in Alzheimer’s disease(AD)patients.Moreover,Aβdeposits have been identified in peripheral tissues.However,the relevance of peripheral Aβ(misfolded or not)in pathological situations,and the temporal appearance of these pathological fluctuations,are not well understood.The presence of misfolded Aβin peripheral compartments raises concerns on potential inter-individual transmissions considering the well-reported prion-like properties of this disease-associated protein.The latter is supported by multiple reports demonstrating that Aβmisfolding can be transmitted between humans and experimental animals through multiple routes of exposure.In this mini-review,we discuss the potential implications of peripheral,disease-associated Aβin disease mechanisms,as well as in diagnostic and therapeutic approaches.

关键词： therapeutic amyloid latter

Misfolded amyloid-βstrains and their potential roles in the clinical and pathological variability of Alzheimer’s disease

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Neural Regeneration Research 2023年第1期18卷 119-120页

作者： Sara Kelley Nelson Perez-Urrutia rodrigo morales Department of Neurology University of Texas Health Science Center at HoustonHoustonTXUSA Centro Integrativo de Biologia y Quimica Aplicada(CIBQA) Universidad Bernardo O’HigginsSantiagoChile

Potential causes for the clinical and pathological variability observed in Alzheimer’s disease(AD):AD is an age-related neurodegenerative disorder characterized by the impairment of cognitive functions such as memory,learning,and reasoning.These commonly described clinical symptoms are due to particular pathological changes in the brain,including inflammation,synaptic loss,and neuronal death.These changes are a consequence of the accumulation of abnormally folded amyloid-β(Aβ)and tau proteins in specific areas of the central nervous system.Considering the progressive aging of the world’s population,the number of people affected by AD is expected to substantially and consistently increase in the coming years.This positions AD as one of the main public health challenges in the near future.

关键词： clinical Alzheimer amyloid

Effect of the Type of Pasture on the Meat Characteristics of Chilote Lambs

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Food and Nutrition Sciences 2014年第7期5卷 635-644页

作者： Jorge Ramírez-Retamal rodrigo morales M. Eugenia Martínez rodrigo de la Barra Escuela de Graduados Facultad Ciencias Agrarias Universidad Austral de Chile Becario CONICYT Valdivia Chile Instituto de Investigaciones Agropecuarias (INIA) Osorno Chile Instituto de Investigaciones Agropecuarias (INIA) Castro Chile Instituto de Investigaciones Agropecuarias (INIA) Osorno Chile

Chilote sheep are a native breed from Chiloé Archipelago in the southern Chile. They are descendants from sheep originally introduced by the Spaniards in the 1600s, and then evolved in a harsh environment in relative isolation from the continent. There is little information about the quality of the meat of the Chilote lambs (Ch). The objective of this study was to compare the quality of Ch lamb meat with two types of marginal pastures. The two treatments were: 1) Ch lambs, naturalized grassland (n = 13) and 2) Ch lambs, rangeland (n = 11). Rangeland is composed of both grasses and native shrubs. All lambs were kept with their mothers until slaughter at 90 days of age. Instrumental color, shear force, pH levels, and chemical and fatty acid content were analyzed. The pasture type did affect the results, given that Ch lambs fed on naturalized pasture had a lower shear force and higher intramuscular fat levels whereas Ch lambs fed on rangeland pasture showed higher percentages of n-3, n-6 fatty acids and Polyunsaturated fatty acids. However, the concentrations of fatty acids were similar in both groups. The results indicated some evidences that the type of pasture of Chiloe archipelago confers specific differences of quality that could form the basis to generate a premium product.

关键词： Rangeland Feeding Quality Fatty Acids

Estimating prion concentration in fluids and tissues by quantitative PMCA

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Estimating prion concentration in fluids and tissues by quan...

Observation of dipolar transport in one-dimensional photonic lattices

中国畜牧兽医学会2010年学术年会——第二届中国兽医临...

作者： rodrigo morales Marcelo A Barria Claudio Soto Mitchell Center for Alzheimer’s Disease and Related Brain Disorders Department of NeurologyUniversity of Texas Houston Medical School

＜正＞Aims:Estimating prion concentration in fluids and tissues after prion infection. Methods:Prions,the proteinaceous infectious agent responsible for prion diseases,can be detected with high sensitivity by protein misfolding cyclic amplification（PMCA） technology. Results:We describe a quantitative PMCA procedure to calculate the concentration of very low levels of prions in biological samples. Conclusions:Using the procedure of quantitative PMCA,we determined the quantities of misfolded prion protein （PrPSc） in brain,spleen,blood and urine of scrapie-affected hamsters.

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Science Bulletin 2017年第5期62卷 339-344页

作者： Camilo Cantillano Luis morales-Inostroza Bastián Real Santiago Rojas-Rojas Aldo Delgado Alexander Szameit rodrigo A.Vicencio Departamento de Física MSI-Nucleus on Advanced Opticsand Center for Optics and Photonics(CEFOP)Facultad de CienciasUniversidad de ChileSantiagoChile Center for Optics and Photonics and MSI-Nucleus on Advanced Optics Universidad de ConcepciónCasilla 160-C ConcepcionChile Institute for Physics University of RostockD-18059 RostockGermany

We experimentally study the transport properties of dipolar and fundamental modes on one dimensional(1D) coupled waveguide arrays. By carefully modulating a wide optical beam, we are able to effectively excite dipolar or fundamental modes to study discrete diffraction(single-site excitation) and gaussian beam propagation(multi-site excitation plus a phase gradient). We observe that dipolar modes experience a larger spreading area due to an effective larger coupling constant, which is found to be more than two times larger than the one for fundamental modes. Additionally, we study the effect of non-diagonal disorder and find that while fundamental modes are already trapped on a weakly disorder array, dipoles are still able to propagate across the system.

关键词： Photonic lattices Waveguide arrays Wave propagation Integrated optics

Helicobacter pylori HopE and HopV porins present scarce expression among clinical isolates

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World Journal of Gastroenterology 2010年第3期16卷 320-329页

作者： Maritza Lienlaf Juan Pablo morales María Inés Díaz rodrigo Díaz Elsa Bruce Freddy Siegel Gloria León Paul R Harris Alejandro Venegas Microbial Pathogenesis and Vaccine Biotechnology Laboratory Department of Molecular Genetics and MicrobiologyFaculty of Biological SciencesPontificia Universidad Católica de Chile Gastroenterology Unit Faculty of MedicineUniversidad Austral de Chile Institute of Biochemistry Faculty of SciencesUniversidad Austral de Chile Department of Pediatrics School of MedicinePontificia Universidad Católica de Chile

AIM:To evaluate how widely Helicobacter pylori (H. pylori ) HopE and HopV porins are expressed among Chilean isolates and how seroprevalent they are among infected patients in Chile.METHODS: H. pylori hopE and hopV genes derived from strain CHCTX-1 were cloned by polymerase chain reaction (PCR), sequenced and expressed in Escherichia coli AD494 (DE3). Gel-purified porins were used to prepare polyclonal antibodies. The presence of both genes was tested by PCR in a collection of H. pylori clinical isolates and their expression was detected in lysates by immunoblotting. Immune responses against HopE, HopV and other H. pylori antigens in sera from infected and non-infected patients were tested by Western blotting using these sera as f irst antibody on recombinant H. pylori antigens.RESULTS: PCR and Western blotting assays revealed that 60 and 82 out of 130 Chilean isolates carried hopE and hopV genes, respectively, but only 16 and 9, respectively, expressed these porins. IgG serum immunoreactivity evaluation of 69 H. pylori-infected patients revealed that HopE and HopV were infrequently recognized (8.7% and 10.1% respectively) compared to H. pylori VacA (68.1%) and CagA (59.5%) antigens. Similar values were detected for IgA serum immunoreactivity against HopE (11.6%) and HopV (10.5%) although lower values for VacA (42%) and CagA (17.4%) were obtained when compared to the IgG response.CONCLUSION: A scarce expression of HopE and HopV among Chilean isolates was found, in agreement with the infrequent seroconversion against these antigens when tested in infected Chilean patients.

关键词： Helicobacter pylori Gene expression HopE and HopV porins Antigens Immune response

Duodenal biopsy may be avoided when high transglutaminase antibody titers are present

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世界胃肠病学杂志：英文版 2009年第38期15卷 4775-4780页

作者： Santiago Vivas Jose G Ruiz de morales Sabino Riestra Laura Arias Dolores Fuentes Noemi Alvarez Sara Calleja Mercedes Hernando Blanca Herrero Javier Casqueiro Luis rodrigo Department of Gastroenterology Hospital de León Institute of Biomedicine University of León Immunology Section Hospital de León Department of Gastroenterology Hospital Universitario Central de Asturias Department of Pathology Hospital de León Department of Pediatrics Hospital de León Faculty of Biology and Environmental Sciences University of León

AIM:To evaluate the predictive value of tissue transglutaminase (tTG) antibodies for villous atrophy in adult and pediatric populations to determine if duodenal biopsy can be avoided.METHODS: A total of 324 patients with celiac disease (CD; 97 children and 227 adults) were recruited prospectively at two tertiary centers. Human IgA class anti-tTG antibody measurement and upper gastrointestinal endoscopy were performed at diagnosis. A second biopsy was performed in 40 asymptomatic adults on a gluten-free diet (GFD) and with normal tTG levels.RESULTS: Adults showed less severe histopathology (26% vs 63%, P<0.0001) and lower tTG antibody titers than children. Levels of tTG antibody correlated with Marsh type in both populations (r=0.661, P<0.0001). Multiple logistic regression revealed that only tTG antibody was an independent predictor for Marsh type 3 lesions, but clinical presentation type and age were not. A cut-off point of 30 U tTG antibody yielded the highest area under the receiver operating characteristic curve (0.854). Based on the predictive value of this cut-off point, up to 95% of children and 53% of adults would be correctly diagnosed without biopsy. Despite GFDs and decreased tTG antibody levels, 25% of the adults did not recover from villous atrophy during the second year after diagnosis.CONCLUSION: Strongly positive tTG antibody titers might be sufficient for CD diagnosis in children. However, duodenal biopsy cannot be avoided in adults because disease presentation and monitoring are different.

关键词：转谷氨酰胺酶十二指肠抗体滴度活检

Glucocorticosteroid therapy in inflammatory bowel diseases: From clinical practice to molecular biology

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World Journal of Gastroenterology 2017年第36期23卷 6628-6638页

作者： Karen Dubois-Camacho Payton A Ottum Daniel Franco-Munoz Marjorie De la Fuente Alejandro Torres-Riquelme David Díaz-Jiménez Mauricio Olivares-morales Gonzalo Astudillo rodrigo Quera Marcela A Hermoso Innate Immunity Laboratory Immunology ProgramInstitute of Biomedical SciencesFaculty of MedicineUniversidad de Chile Neuroimmunology Laboratory Immunology ProgramInstitute of Biomedical SciencesFaculty of MedicineUniversidad de Chile Division of Research Clínica Las Condes Gastroenterology Department Inflammatory Bowel Disease ProgramClínica Las Condes

Inflammatory bowel diseases(IBDs),such as ulcerative colitis and Crohn's disease,are chronic pathologies associated with a deregulated immune response in the intestinal mucosa,and they are triggered by environmental factors in genetically susceptible individuals.Exogenous glucocorticoids(GCs)are widely used as anti-inflammatory therapy in IBDs.In the past,patients with moderate or severe states of inflammation received GCs as a first line therapy with an important effectiveness in terms of reduction of the disease activity and the induction of remission.However,this treatment often results in detrimental side effects.This downside drove the development of second generation GCs and more precise(non-systemic)drugdelivery methods.Recent clinical trials show that most of these new treatments have similar effectiveness to first generation GCs with fewer adverse effects.The remaining challenge in successful treatment of IBDs concerns the refractoriness and dependency that some patients encounter during GCs treatment.A deeper understanding of the molecular mechanisms underlying GC response is key to personalizing drug choice for IBDs patients to optimize their response to treatment.In this review,we examine the clinical characteristics of treatment with GCs,followed by an in depth analysis of the proposed molecular mechanisms involved in its resistance and dependence associated with IBDs.This thorough analysis of current clinical and biomedical literature may help guide physicians in determining a course of treatment for IBDs patients and identifies important areas needing further study.

关键词： Inflammatory bowel diseases Ulcerative colitis Crohn's disease Glucocorticoid dependence Glucocorticoid resistance

Evaluation of VEGF gene polymorphisms and proliferative diabetic retinopathy in Mexican population

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International Journal of Ophthalmology(English edition) 2017年第1期10卷 135-139页

作者： Roberto Gonzalez-Salinas Maria C Garcia-Gutierrez Gerardo Garcia-Aguirre Virgilio morales-Canton Raul Velez-Montoya Vidal R Soberon-Ventura Victoria Gonzalez rodrigo Lechuga Pablo Garcia-Solis David G Garcia-Gutierrez Marco Vinicio Garcia-Solis Manuel Saenz de Viteri Juan C Solis-S Biomedical Research Department Autonomous University of QueretaroQueretaro 76170Mexico Retina Department Asociation to Prevent Blindness in MexicoMexico City 04030Mexico Research Department Asociation to Prevent Blindness in MexicoMexico City 04030Mexico Retina Department General Hospital of Queretaro(ISSSTE)Queretaro 76000Mexico Universidad La Salle School of Medicine Mexico City 06140Mexico

AIM： To assess if the included vascular endothelial growth factor （VEGF） polymorphisms rs3025035, rs3025021 and rs2010963 are associated to proliferative retinopathy in a Mexican population with type 2 diabetes mellitus （T2DM）. METHODS： A case-control study was conducted in adult individuals with T2DM associated to proliferative retinopathy or non-proliferative retinopathy from Oct. 2014 to Jun. 2015 from the Retina Department of the Asociation to Prevent Blindness in Mexico. The selected patients were adults with a diagnosis of T2DM ≥5y. All subjects had a comprehensive ocular examination and the classification of the retinopathy severity was made considering the Early Treatment Diabetic Retinopathy Study （ETDRS） standardization protocols. Genomic DNA was extracted from whole fresh blood. All samples were genotyped by qPCR for selected VEGF polymorphisms. Hardy-Weinberg equilibrium was calculated by comparing Chi-square values between the expected and the observed values for genotype counts.RESULTS： In total 142 individuals were enrolled, 71 individuals with T2DM and associated proliferative retinopathy and 71 individuals with non-proliferative retinopathy. One-sided Fisher’s exact test was performed for rs3025021 [OR （95% CI）=0.44（0.08-2.2）; P=0.25] and rs2010963 [OR （95% CI）=0.63（0.25-1.6）; P=0.23]. The minor allelic frequencies obtained were 26% for rs3025021, 10% for rs3025035 and 61% for rs2010963. The pairwise linkage disequilibrium between the three SNP was assessed, and was as follows： rs3025021 vs rs3025035： D’=1.0, r2=0.1043, P≤0.0001; rs3025021 vs rs2010963： D’=0.442, r2=0.0446, P=0.149; rs3025035 vs rs2010963： D’=0.505, r2=0.0214, P=0.142.CONCLUSION： This is the first analysis involving VEGF polymorphisms and proliferative diabetic retinopathy in a Mexican population. A major finding of the present study is that none of the polymorphisms studied was significantly associated with proliferative retinopathy. Based on these results, we can infer that different populations have different associations for

关键词： vascular endothelial growth factor polymor-phism proliferative diabetic retinopathy non-proliferative diabetic retinopathy rs3025021 rs3025035 rs2010963