Arturo Santos

Tecnológico de Monterrey

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Juan Armendáriz‐Borunda

Universidad de Guadalajara

José Navarro‐Partida

Tecnológico de Monterrey

Ana Sandoval-Rodríguez

Universidad de Guadalajara

Hugo Christian Monroy-Ramírez

Universidad de Guadalajara

Juan Carlos Altamirano-Vallejo

Tecnológico de Monterrey

Alejandro González‐De la Rosa

Tecnológico de Monterrey

Marina Galicia‐Moreno

Universidad de Guadalajara

Jesús García‐Bañuelos

Universidad de Guadalajara

Abril Bernardette Martínez-Rizo

Universidad Autónoma de Nayarit

Alejandra Meza-Ríos

Universidad de Guadalajara

Cooperative Institutions

Universidad de Guadalajara

115

Tecnológico de Monterrey

Hospital Civil de Guadalajara

Johns Hopkins University

University of Southern California

Centro de Retina Médica y Quirúrgica

Universidad Autónoma de Nayarit

Secretaría de Salud de Jalisco

Second Sight Medical Products

Mexican Social Security Institute

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Proapoptotic TLR4 polymorphism is more frequent in Stargardt disease patients. A family study.

Investigative Ophthalmology & Visual Science (2017)

Gonzalez-de la Rosa Alejandro José Navarro‐Partida Nicole Macriz-Romero Ramses Rosales Diaz Abril Bernardette Martínez-Rizo

Stargardt disease

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Prolonged-release pirfenidone prevents myocardial fibrosis in a mouse nonalcoholic steatohepatitis model

Annals of Hepatology (2020)

Jorge Gutiérrez‐Cuevas Ana Sandoval-Rodríguez C. Monroy-Ramírez Arturo Santos Juan Armendáriz‐Borunda

Nonalcoholic steatohepatitis

Pirfenidone

Steatohepatitis

Myocardial fibrosis

10.1016/j.aohep.2020.08.020

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Citations (2)

Topical Triamcinolone Acetonide-Loaded Liposomes Formulation Used as an Adjuvant to Intravitreal Ranibizumab Therapy for Neovascular Age Related Macular Degeneration

José Navarro‐Partida Juan Carlos Altamirano-Vallejo Luis Abraham Aceves Franco Jesús Hernán González-Cortés Sergio Hernandez Da Mota

Novel strategies have been developed to reduce or to avoid the intravitreal injections (IVTs) of the antiangiogenic (ranibizumab; RBZ) and the anti-inflammatory (triamcinolone acetonide; TA) agents used to treat vitreoretinal diseases. One of the strategies include liposomes. In this study, it was evaluated the safety and efficacy of topical triamcinolone-loaded liposomes formulation (TALF) as an adjuvant to intravitreal RBZ therapy in treatment-naive patients with neovascular age related macular degeneration (nAMD). Subjects were randomly assigned to the RBZ-TALF or the RBZ-pro re nata (RBZ-PRN) group. Patients from the RBZ-TALF group were instructed to apply TALF for a 12-month period after a single dose of RBZ. Patients from the RBZ-PRN group received three monthly RBZ-IVTs. Retreatment with RBZ was considered in case of nAMD reactivation. Related to safety, non-ocular abnormalities were observed during TALF therapy. Owing to the efficacy, non-significant differences are identified in visual acuity or central foveal thickness when the RBZ-PRN and RBZ-TALF groups are compared. Importantly the average number of RBZ injections was significantly lower in the RBZ-TALF group (2.5 ± 1.4 vs 6.1 ± 1.3 IVTs; p=0004). Therefore, TALF used as an adjuvant to RBZ reduce the number of RBZ-IVTs retreatment with optimal visual and anatomic results.

10.20944/preprints202106.0585.v1

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Surgical Results in Ocriplasmin Candidates With Symptomatic Vitreomacular Traction Syndrome

Current Eye Research (2017)

Darío H. Vásquez Juan Carlos Altamirano Angel Casaus Rodrigo A. Del Valle Roberto González

Purpose: To report surgical outcomes in a series of cases with symptomatic vitreomacular traction that met MIVI-TRUST (Microplasmin for intravitreous injection-traction release without surgical treatment) criteria for ocriplasmin use who underwent primary 25-gauge vitrectomy.Materials and Methods: A single-center retrospective chart review study was performed in patients who underwent primary 25-gauge vitrectomy for symptomatic vitreomacular traction (VTM) from January 2013 through January 2016. Pre- and postoperative visual acuity (measured by the early treatment diabetic retinopathy acuity test), and posterior hyaloid focal attachment to the macula (demonstrated by high-definition optical coherence tomography) were analyzed. In addition, intra- and postoperative complications were obtained from medical records.Results: Fifteen consecutive cases of symptomatic VMT traction that underwent primary 25-gauge vitrectomy were included. All met the MIVI-TRUST criteria for ocriplasmin use. In all cases, VMT resolution, macular hole closure, and improvement in best corrected visual acuity (BCVA) were observed. Mean visual acuity improved from 56.53 ± 16.04 letters at baseline to 73.13 ± 7.46 letters at 24 weeks of follow-up. The mean BCVA improvement from baseline was 16.60 letters (range 6–44), which was statistically significant (P < 0.0001). Ten of fifteen patients (66.6%) showed significant improvement of their BCVA to 20/40 or better (70 or more in ETDRS visual acuity test). No significant intra- or postoperative complications were documented.Conclusions: Primary 25-gauge pars plana vitrectomy in eyes with symptomatic vitreomacular traction is able to efficiently resolve VMT and macular holes, improving vision in candidates for intravitreal injection of ocriplasmin. This well-tolerated surgical procedure may be a reliable and predictable alternative for resolving VMT pathology.

10.1080/02713683.2017.1385086

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Adenovirus Biodistribution is Modified in Sensitive Animals Compared to Naïve Animals

Molecular Biotechnology (2020)

Ana Sandoval-Rodríguez Mayra Marta Mena Múgica Jesús García‐Bañuelos Adriana María Salazar-Montes Mary Fafutis‐Morris

Biodistribution

Immunosuppression

10.1007/s12033-020-00247-x

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Pirfenidone Is an Agonistic Ligand for PPARα and Improves NASH by Activation of SIRT1/LKB1/pAMPK

Hepatology Communications (2020)

Ana Sandoval-Rodríguez Hugo Christian Monroy-Ramírez Alejandra Meza-Ríos Jesús García‐Bañuelos José María Vera-Cruz

Nonalcoholic steatohepatitis (NASH) is recognized by hepatic lipid accumulation, inflammation, and fibrosis. No studies have evaluated the prolonged‐release pirfenidone (PR‐PFD) properties on NASH features. The aim of this study is to evaluate how PR‐PFD performs on metabolic functions, and provide insight on a mouse model of human NASH. Male C57BL/6J mice were fed with either normo diet or high‐fat/carbohydrate diet for 16 weeks and a subgroup also fed with PR‐PFD (300 mg/kg/day). An insulin tolerance test was performed at the end of treatment. Histological analysis, determination of serum hormones, adipocytokines measurement, and evaluation of proteins by western blot was performed. Molecular docking, in silico site‐directed mutagenesis, and in vitro experiments using HepG2 cultured cells were performed to validate PR‐PFD binding to peroxisome proliferator–activated receptor alpha (PPAR‐α), activation of PPAR‐α promoter, and sirtuin 1 (SIRT1) protein expression. Compared with the high‐fat group, the PR‐PFD‐treated mice displayed less weight gain, cholesterol, very low density lipoprotein and triglycerides, and showed a significant reduction of hepatic macrosteatosis, inflammation, hepatocyte ballooning, fibrosis, epididymal fat, and total adiposity. PR‐PFD restored levels of insulin, glucagon, adiponectin, and resistin along with improved insulin resistance. Noteworthy, SIRT1–liver kinase B1–phospho‐5′ adenosine monophosphate–activated protein kinase signaling and the PPAR‐α/carnitine O‐palmitoyltransferase 1/acyl‐CoA oxidase 1 pathway were clearly induced in high fat + PR‐PFD mice. In HepG2 cells incubated with palmitate, PR‐PFD induced activation and nuclear translocation of both PPARα and SIRT1, which correlated with increased SIRT1 phosphorylated in serine 47, suggesting a positive feedback loop between the two proteins. These results were confirmed with both synthetic PPAR‐α and SIRT1 activators and inhibitors. Finally, we found that PR‐PFD is a true agonist/ligand for PPAR‐α. Conclusions: PR‐PFD provided an anti‐steatogenic effect and protection for inflammation and fibrosis.

Sirtuin 1

Steatohepatitis

CD36

Resistin

10.1002/hep4.1474

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Citations (43)

Delphinidin Ameliorates Hepatic Triglyceride Accumulation in Human HepG2 Cells, but Not in Diet-Induced Obese Mice

Nutrients (2018)

Marcela Parra-Vargas Ana Sandoval-Rodríguez Roberto Rodriguez‐Echevarría José Alfredo Domínguez‐Rosales Arturo Santos

Anthocyanin consumption is linked to benefits in obesity-related metabolic alterations and non-alcoholic fatty liver disease (NAFLD), though the functional role of delphinidin (Dp) is yet to be established. Therefore, this study examined the effects of Dp on metabolic alterations associated with NAFLD, and molecular mechanisms in HepG2 cells and diet-induced obese mice. Cells incubated with palmitate to induce lipid accumulation, concomitantly treated with Dp, reduced triglyceride accumulation by ~53%, and downregulated gene expression of CPT1A, SREBF1, and FASN without modifying AMP-activated protein kinase (AMPK) levels. C57BL/6Nhsd mice were fed a standard diet (control) or a high-fat/high-carbohydrate diet (HFHC) for 16 weeks. Mice in the HFHC group were subdivided and treated with Dp (HFHC-Dp, 15 mg/kg body weight/day) or a vehicle for four weeks. Dp did not affect body weight, energy intake, hyperglycemia, insulin resistance, or histological abnormalities elicited by the HFHC diet. Furthermore, the messenger RNA (mRNA) expressions of Acaca, and Fasn in hepatic or epididymal adipose tissue, and the hepatic sirtuin 1 (SIRT1)/liver kinase B1 (LKB1)/AMPK and proliferator-activated receptor alpha (PPARα) signaling axis did not significantly change due to the HFHC diet or Dp. In summary, Dp effectively reduced triglyceride accumulation in vitro through the modulation of lipid metabolic gene expression. However, a dose of Dp administrated in mice simulating the total daily anthocyanin intake in humans had no effect on either metabolic alterations or histological abnormalities associated with HFHC diets.

Steatosis

10.3390/nu10081060

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P-2 NASH IS IMPROVED THROUGH MODIFICATIONS IN H3K9 METHYLATION BY PIRFENIDONE ACTING AS JMJD2B DEMETHYLASE ANTAGONIST.

Annals of Hepatology (2024)

Samael Rodríguez Rebeca Rosas Angel Omar Vazquez I. Silva Palacios Ricardo De la Rosa

NASH is characterized by hepatic lipid accumulation and inflammation and Jmjd2b up-regulation has been linked with this illness progression. Pirfenidone is an antifibrotic agent with anti-inflammatory and antioxidant effects recognized to decrease NASH features. Here, we report epigenetics mechanisms related to PFD-induced histone modifications involved in experimental NASH. This study aimed to investigate PFD as an epigenetic regulator in the Jmjd2b pathway by demethylating H3k9me3 in a NASH animal model. Male C57BL/6J mice were fed with either normo-diet, or high fat/carbohydrate-containing diet (HF) for 16 weeks. A HF-subgroup was treated with PFD 300 mg/kg/d from week 8th to the end of protocol. Weight was recorded on weekly basis. Insulin tolerance test was performed at the end of treatment. Dual channel microarrays were hybridized to the Mus musculus genome version with 22,000 genes using hepatic mRNAs. Liver and fat histological analyses were carried out, and liver proteins were analyzed by western blot and Chromatin immunoprecipitation (ChIP). Molecular docking was used to validate binding of PFD to JMJD2BBBBB. Compared with HF group, mice treated with PFD reduced weight gain, hepatic fat accumulation, and epididymal fat. In addition, treatment drastically decreased cholesterol, triglycerides and VLDL, ALT and AST. Inflammatory nodules, fibrosis, and steatosis in liver tissue were also reduced. Besides, PFD modified expression of genes, such as, Jmjd2b, Pparg, Fasn and Srebp1. Likewise, PFD restored the repressive marks in H3k9, suggesting its capacity as an epigenetic regulator by decreasing Jmjd2b protein activity and interacting with its catalytic site (JmjC). PFD played an important role as an epigenetic regulator modifying Jmjd2b activity and improving NASH features.

Demethylase

10.1016/j.aohep.2023.101189

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[Idiopathic macular hole surgery].

PubMed (2011)

Arturo Santos Juan Carlos Altamirano-Vallejo Sonia M. Cisneros-Gómez Alfonso Teramoto-Sera Yael Ileana Morales-Martínez

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History of Demyelinating Optic Neuropathies: Two Centuries of Progress (P2-1.014)

Neurology (2024)