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Item Dataset from: Highly purified and functionally stable in vitro expanded allospecific Tr1 cells expressing immunosuppressive graft-homing receptors as new candidates for cell therapy in solid organ transplantation(Frontiers, 2023-02-24) Arteaga-Cruz, Saúl; Cortés-Hernández, Arimelek; Alvarez Salazar, Evelyn Katy; Rosas-Cortina, Katya; Aguilera-Sandoval, Christian; Morales-Buenrostro, Luis E.; Alberú-Gómez, Josefina M.; Soldevila, GloriaThe development of new strategies based on the use of Tr1 cells has taken relevance to induce long-term tolerance, especially in the context of allogeneic stem cell transplantation. Although Tr1 cells are currently identified by the co-expression of CD49b and LAG-3 and high production of interleukin 10 (IL-10), recent studies have shown the need for a more exhaustive characterization, including co-inhibitory and chemokines receptors expression, to ensure bona fide Tr1 cells to be used as cell therapy in solid organ transplantation. Moreover, the proinflammatory environment induced by the allograft could affect the suppressive function of Treg cells, therefore stability of Tr1 cells needs to be further investigated. Here, we establish a new protocol that allows long-term in vitro expansion of highly purified expanded allospecific Tr1 (Exp-allo Tr1). Our expanded Tr1 cell population becomes highly enriched in IL-10 producers (> 90%) and maintains high expression of CD49b and LAG-3, as well as the co-inhibitory receptors PD-1, CTLA-4, TIM-3, TIGIT and CD39. Most importantly, high dimensional analysis of Exp-allo Tr1 demonstrated a specific expression profile that distinguishes them from activated conventional T cells (T conv), showing overexpression of IL-10, CD39, CTLA-4 and LAG-3. On the other hand, Exp-allo Tr1 expressed a chemokine receptor profile relevant for allograft homing and tolerance induction including CCR2, CCR4, CCR5 and CXCR3, but lower levels of CCR7. Interestingly, Exp-allo Tr1 efficiently suppressed allospecific but not third-party T cell responses even after being expanded in the presence of proinflammatory cytokines for two extra weeks, supporting their functional stability. In summary, we demonstrate for the first time that highly purified allospecific Tr1 (Allo Tr1) cells can be efficiently expanded maintaining a stable phenotype and suppressive function with homing potential to the allograft, so they may be considered as promising therapeutic tools for solid organ transplantation.Item Data_Sheet_1_Genome-Wide Inhibition of Pro-atherogenic Gene Expression by Multi-STAT Targeting Compounds as a Novel Treatment Strategy of CVDs.docx(Frontiers, 2018-09-18) Plens-Galaska, Martyna; Ramos Gonzalez, Mariella; Malgorzata, Szelag; Collado, Aida; Marques, Patrice; Vallejo, Susana; Wesoly, Joanna; Jesus Sanz, María; Peiró, Concepción; Bluyssen, Hans A. R.Cardiovascular diseases (CVDs), including atherosclerosis, are globally the leading cause of death. Key factors contributing to onset and progression of atherosclerosis include the pro-inflammatory cytokines Interferon (IFN)α and IFNγ and the Pattern Recognition Receptor (PRR) Toll-like receptor 4 (TLR4). Together, they trigger activation of Signal Transducer and Activator of Transcription (STAT)s. Searches for compounds targeting the pTyr-SH2 interaction area of STAT3, yielded many small molecules, including STATTIC and STX-0119. However, many of these inhibitors do not seem STAT3-specific. We hypothesized that multi-STAT-inhibitors that simultaneously block STAT1, STAT2, and STAT3 activity and pro-inflammatory target gene expression may be a promising strategy to treat CVDs. Using comparative in silico docking of multiple STAT-SH2 models on multi-million compound libraries, we identified the novel multi-STAT inhibitor, C01L_F03. This compound targets the SH2 domain of STAT1, STAT2, and STAT3 with the same affinity and simultaneously blocks their activity and expression of multiple STAT-target genes in HMECs in response to IFNα. The same in silico and in vitro multi-STAT inhibiting capacity was shown for STATTIC and STX-0119. Moreover, C01L_F03, STATTIC and STX-0119 were also able to affect genome-wide interactions between IFNγ and TLR4 by commonly inhibiting pro-inflammatory and pro-atherogenic gene expression directed by cooperative involvement of STATs with IRFs and/or NF-κB. Moreover, we observed that multi-STAT inhibitors could be used to inhibit IFNγ+LPS-induced HMECs migration, leukocyte adhesion to ECs as well as impairment of mesenteric artery contractility. Together, this implicates that application of a multi-STAT inhibitory strategy could provide great promise for the treatment of CVDs.Item Twenty-one different avian species identified as possible reservoir of avian influenza virus in Lima Metropolitan Region, Peru, Pacific flyway, South America.(PLOS, 2022-06) Castro Sanguinetti, Gina Ruth; Marques Simas, Paulo Vitor; Apaza-Chiara, Ana Paola; Callupe-Leyva, Jose Alonso; Rondon-Espinoza , Juan Alexander; Gavidia, Cesar M.; More-Bayona, Juan Anderson; Gonzalez Veliz, Rosa Isabel; Vakharia, Vikram N.; Eliana Icochea, MariaTwenty-one different avian species identified as possible reservoir of avian influenza virus in Lima Metropolitan Region, Peru, Pacific flyway, South America.Item Status of samples tested positives by hemagglutination test followed by confirmation using rapid antigen and PCR tests for influenza A virus.(Public Library of Science, 2022-06-07) Castro-Sanguinetti, Gina R.; Marques Simas, Paulo Vitor; Apaza-Chiara, Ana Paola; Callupe-Leyva, Jose Alonso; Rondon-Espinoza, Juan Alexander; Gavidia, Cesar M.; More-Bayona, Juan Anderson; Gonzalez Veliz, Rosa Isabel; Vakharia, Vikram N.; Eliana Icochea, MariaStatus of samples tested positives by hemagglutination test followed by confirmation using rapid antigen and PCR tests for influenza A virus.Item Evaluation of abortions spontaneously induced by Neospora caninum and risk factors in dairy cattle from Lima, Peru(SciELO journals, 2019-06-18) Serrano-Martínez, Marcos Enrique; Burga Cisterna, Cesar Abel; Evaristo Romero, Roberto Carlos; Quispe Huacho, Marco Antonio; Matienzo Bermabé, Alessandra; Llanco Albornoz, Luis AntonioOur objective was to identify the direct and indirect presence of Neospora caninum in dairy cattle and their aborted fetuses from Lima, Peru. A total 219 blood samples obtained from dairy cattle with records of spontaneous abortion were collected to detect antibodies against N. caninum in serum with indirect ELISA and search for risk-factor associations. 68 fetal aborted tissue samples of these cows were analyzed by PCR, indirect ELISA and histopathology assay to detect N. caninum presence. The prevalence ratio (PR) and 95% confidence intervals (CI) were estimated. Univariate analysis was performed using the chi-squared test. Among the 68 aborted fetuses collected, 10 (15%) were positive in at least two diagnostic tests. Among 219 serum samples, 46.6% (95% CI: 40.0%-53.3%) were positive. Cows with 4 years or older (PR: 7.10; 95% CI: 4.89-10.67) and multiparous (PR: 1.76; 95% CI: 1.11-2.80) were found to be more likely to possess N. caninum antibodies. This study detects presence of N. caninum in dairy cattle and their aborted fetus from Lima valley, suggesting biosecurity management improve to neosporosis control.Item Supplemental Table S4 from Evaluation of Multiple Breast Cancer Polygenic Risk Score Panels in Women of Latin American Heritage(American Association for Cancer Research (AACR), 2025-02-06) Huang, Xiaosong; Lott, Paul C.; Hu, Donglei; Zavala, Valentina A.; Jamal, Zoeb N.; Vidaurre, Tatiana; Casavilca Zambrano, Sandro Angel Aníbal; Navarro Vásquez, Jeannie; Castañeda, Carlos A.; Valencia, Guillermo; Morante, Zaida; Calderón, Mónica; Abugattas, Julio E.; Fuentes, Hugo A.; Liendo-Picoaga, Ruddy; Cotrina, Jose M.; Neciosup, Silvia P.; Rioja Viera, Patricia; Salinas, Luis A.; Galvez-Nino, Marco; Huntsman, Scott; Sanchez, Sixto E.; Williams, Michelle A.; Gelaye, Bizu; Estrada-Florez, Ana P.; Polanco-Echeverry, Guadalupe; Echeverry, Magdalena; Velez, Alejandro; Carmona-Valencia, Jenny A.; Bohorquez-Lozano, Mabel E.; Torres, Javier; Cruz, Miguel; Ho, Weang-Kee; Hwang Teo, Soo; Chee Tai, Mei; John, Esther M.; Haiman, Christopher A.; Conti, David V.; Chen, Fei; Torres-Mejía, Gabriela; Kushi, Lawrence H.; Neuhausen, Susan L.; Ziv, Elad; Carvajal-Carmona, Luis G.; Fejerman, LauraA substantial portion of the genetic predisposition for breast cancer is explained by multiple common genetic variants of relatively small effect. A subset of these variants, which have been identified mostly in individuals of European (EUR) and Asian ancestries, have been combined to construct a polygenic risk score (PRS) to predict breast cancer risk, but the prediction accuracy of existing PRSs in Hispanic/Latinx individuals (H/L) remain relatively low. We assessed the performance of several existing PRS panels with and without addition of H/L-specific variants among self-reported H/L women. PRS performance was evaluated using multivariable logistic regression and the area under the ROC curve. Both EUR and Asian PRSs performed worse in H/L samples compared with original reports. The best EUR PRS performed better than the best Asian PRS in pooled H/L samples. EUR PRSs had decreased performance with increasing Indigenous American (IA) ancestry, while Asian PRSs had increased performance with increasing IA ancestry. The addition of two H/L SNPs increased performance for all PRSs, most notably in the samples with high IA ancestry, and did not impact the performance of PRSs in individuals with lower IA ancestry. A single PRS that incorporates risk variants relevant to the multiple ancestral components of individuals from Latin America, instead of a set of ancestry-specific panels, could be used in clinical practice. The results highlight the importance of population-specific discovery and suggest a straightforward approach to integrate ancestry-specific variants into PRSs for clinical application.Item DataSheet_1_Preclinical Assessment of IgY Antibodies Against Recombinant SARS-CoV-2 RBD Protein for Prophylaxis and Post-Infection Treatment of COVID-19.docx(Frontiers, 2022-05) Agurto-Arteaga, Andres; Poma-Acevedo, Astrid; Rios-Matos, Dora; Choque-Guevara, Ricardo; Montesinos-Millán, Ricardo; Montalván, Ángela; Isasi-Rivas, Gisela; Cauna-Orocollo, Yudith; Cauti-Mendoza, María de Grecia; Pérez-Martínez, Norma; Gutierrez-Manchay, Kristel; Ramirez-Ortiz, Ingrid; Núñez-Fernández, Dennis; Salguedo-Bohorquez, Mario I.; Quiñones-Garcia, Stefany; Fernández Díaz, Manolo; Guevara Sarmiento, Luis A.; Zimic, Mirko; COVID-19 Working Group in PeruWithin the framework of the current COVID-19 pandemic, there is a race against time to find therapies for the outbreak to be controlled. Since vaccines are still tedious to develop and partially available for low-income countries, passive immunity based on egg-yolk antibodies (IgY) is presented as a suitable approach to preclude potential death of infected patients, based on its high specificity/avidity/production yield, cost-effective manufacture, and ease of administration. In the present study, IgY antibodies against a recombinant RBD protein of SARS-CoV-2 were produced in specific-pathogen-free chickens and purified from eggs using a biocompatible method. In vitro immunoreactivity was tested, finding high recognition and neutralization values. Safety was also demonstrated prior to efficacy evaluation, in which body weight, kinematics, and histopathological assessments of hamsters challenged with SARS-CoV-2 were performed, showing a protective effect administering IgY intranasally both as a prophylactic treatment or a post-infection treatment. The results of this study showed that intranasally delivered IgY has the potential to both aid in prevention and in overcoming COVID-19 infection, which should be very useful to control the advance of the current pandemic and the associated mortality.