Article
Multidisciplinary Sciences
Helena Costa-Verdera, Fanny Collaud, Christopher R. Riling, Pauline Sellier, Jayme M. L. Nordin, G. Michael Preston, Umut Cagin, Julien Fabregue, Simon Barral, Maryse Moya-Nilges, Jacomina Krijnse-Locker, Laetitia van Wittenberghe, Natalie Daniele, Bernard Gjata, Jeremie Cosette, Catalina Abad, Marcelo Simon-Sola, Severine Charles, Mathew Li, Marco Crosariol, Tom Antrilli, William J. Quinn, David A. Gross, Olivier Boyer, Xavier M. Anguela, Sean M. Armour, Pasqualina Colella, Giuseppe Ronzitti, Federico Mingozzi
Summary: Hepatic-directed gene therapy with adeno-associated virus (AAV) vectors enhances bioavailability of acid alpha-glucosidase (GAA) compared with enzyme replacement therapy (ERT), resulting in improved rescue of Pompe disease phenotype in mice and broad enzyme distribution in mice and non-human primates.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Qian-Fang Meng, Wanbo Tai, Mingyao Tian, Xinyu Zhuang, Yuanwei Pan, Jialin Lai, Yangtao Xu, Zhiqiang Xu, Min Li, Guangyu Zhao, Guang-Tao Yu, Guocan Yu, Rongchang Chen, Ningyi Jin, Xiao Li, Gong Cheng, Xiaoyuan Chen, Lang Rao
Summary: Researchers have developed an inhalation delivery system using engineered neutrophil nanovesicles to deliver dexamethasone (DEX) for enhanced treatment of COVID-19. The system targets macrophages and neutralizes broad-spectrum cytokines, showing improved effects against lung inflammation and injury. Inhalation administration of nanoDEX produced better results than intravenous administration, making it a safe and effective platform for respiratory diseases.
Article
Biochemistry & Molecular Biology
Yaswanthi Yanamadala, Mahdi Y. Saleh, Afrika A. Williams, Yuri Lvov, Teresa A. Murray
Summary: The blood-brain barrier prevents most therapeutic drugs from entering the brain, but drugs loaded within halloysite nanotubes can overcome this barrier. Halloysite nanotubes, with their needle-like shape, were used as a nano-torpedo to deliver drugs across the blood-brain barrier when administered intranasally. By loading halloysite nanotubes with diazepam or xylazine and delivering them to mice intranasally, sedative effects were observed. This study confirms that halloysite can permeate the blood-brain barrier to deliver drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Hirotaka Fukami, Jun Morinaga, Hironori Nakagami, Hiroki Hayashi, Yusuke Okadome, Eiji Matsunaga, Tsuyoshi Kadomatsu, Haruki Horiguchi, Michio Sato, Taichi Sugizaki, Keishi Miyata, Daisuke Torigoe, Masashi Mukoyama, Ryuichi Morishita, Yuichi Oike
Summary: This study assessed the durability and booster effects of an ANGPTL3 vaccine, which showed efficacy for over one year and maintained suppression of circulating triglyceride levels without major adverse effects on important organs.
Article
Chemistry, Multidisciplinary
Qiang Lu, Yue Zhou, Min Xu, Xiaoyang Liang, Huaqing Jing, Xinxing Wang, Nan Li
Summary: The engineered sequential delivery strategy of Au NS@CAR-HA effectively targeted hepatic stellate cells by releasing CAR and utilizing the ROS scavenging capability of Au NS to regulate cell proliferation and activation, presenting a promising new approach for hepatic fibrosis treatment.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Food Science & Technology
Ryota Ojiro, Hiromu Okano, Shunsuke Ozawa, Hiroshi Yamagata, Xinyu Zou, Qian Tang, Meilan Jin, Kazuaki Sasaki, Toshinori Yoshida, Tomoya Yoshinari, Makoto Shibutani
Summary: The study investigated the pharmacokinetics and repeated oral toxicity of enniatin B (ENNB) in mice. ENNB showed high bioavailability after oral dosing, with elimination half-life and fecal excretion. The 28-day toxicity study revealed no adverse effects in mice at a dose of 30 mg/kg BW/day.
FOOD AND CHEMICAL TOXICOLOGY
(2023)
Article
Nanoscience & Nanotechnology
Qin Yang, Tiantian Tan, Qin He, Chenqi Guo, Dan Chen, Yulu Tan, Jiaxing Feng, Xu Song, Tao Gong, Jia Li
Summary: This study developed a novel nanosuspension loaded with silybin and silybin meglumine salt to improve the therapeutic effect against hepatic fibrosis. The results showed that the nanosuspension inhibited hepatic fibrosis both in vitro and in vivo, and targeted activated hepatic stellate cells. This innovative approach may have great potential for the treatment of hepatic fibrosis.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Maria Espinosa-Velasco, Marina D. Reguilon, Marina Bellot, Nuria Nadal-Gratacos, Xavier Berzosa, Pol Puigseslloses, Cristian Gomez-Canela, Marta Rodriguez-Arias, David Pubill, Jordi Camarasa, Elena Escubedo, Raul Lopez-Arnau
Summary: The research demonstrates that acute use of NEP can lead to anxiolytic effects, aggressive behavior, and social exploration deficits, which persist during withdrawal. Furthermore, repeat use of NEP can result in hyperthermia and depressive symptoms, possibly due to decreases in serotonin and noradrenaline levels. Additionally, the long-term increase in Delta FosB levels in the striatum after chronic NEP use indicates a high risk of dependence.
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Danielle Weber-Adrian, Rikke Hahn Kofoed, Joseph Silburt, Zeinab Noroozian, Kairavi Shah, Alison Burgess, Shawna Rideout, Sebastian Kuegler, Kullervo Hynynen, Isabelle Aubert
Summary: Non-surgical gene delivery to the brain using AAV6-syn-GFP with MRIgFUS resulted in lower off-target biodistribution in the liver compared to AAV9 and AAV1&2, while providing neuronal GFP expression in the striatum and hippocampus.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Seyoung Kim, Daniel J. Fesenmeier, Sungwan Park, Sandra E. Torregrosa-Allen, Bennett D. Elzey, You-Yeon Won
Summary: This study investigates the clearance pathways and kinetics of amphiphilic poly(styrene-block-ethylene glycol) (PS-PEG) nanoparticles in the lungs. The results demonstrate that PS-PEG nanoparticles have a prolonged retention time in the lungs and are cleared through both mucociliary escalator mechanism and alveolar clearance by macrophages. Additionally, a portion of the nanoparticles translocates directly into the circulation.
Article
Medicine, Research & Experimental
Erawan Borkham-Kamphorst, Ute Haas, Manuela Pinoe-Schmidt, Ali T. Abdallah, Ralf Weiskirchen
Summary: Our study revealed that LCN2 plays an important role in chronic inflammation and fibrosis, with levels correlating with hepatic inflammation rather than fibrosis. Chronic mineral-oil administration induces hepatic inflammation through innate immune responses via myeloid cell activation. Lcn2 null mice exhibit less inflammation due to defective genes involved in myeloid cell activation, leading to mitigation of liver fibrosis.
LABORATORY INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Zhiqiang Fang, Hao Xu, Juanli Duan, Bai Ruan, Jingjing Liu, Ping Song, Jian Ding, Chen Xu, Zhiwen Li, Kefeng Dou, Lin Wang
Summary: Nonalcoholic fatty liver disease (NAFLD) lacks effective treatment. Tamoxifen, which is commonly used as chemotherapy for solid tumors, was found to protect hepatocytes against lipotoxicity and improve glucose and insulin intolerance in mice with NAFLD. However, tamoxifen did not improve inflammation and fibrosis in these models. The therapeutic effect of tamoxifen on NAFLD was not gender or ER dependent, and it was found to inactivate the JNK/MAPK signaling pathway in hepatocytes to improve NAFLD.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Qinxi Li, Bangcheng Zhao, Wanxin Li, Yao He, Xun Tang, Ting Zhang, Zhihui Zhong, Qiangwen Pan, Yingqian Zhang
Summary: Mental disorders have a high incidence and recurrence rate, and some patients do not respond to drug medication. The study found that different methods of drug administration have varying effects on behaviors and drug efficacy. Gastric administration induces CUMS-like behaviors that negatively affect drug efficacy.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Nutrition & Dietetics
Yuko Ishii, Orie Muta, Tomohiro Teshima, Nayuta Hirasima, Minayu Odaka, Taiki Fushimi, Yasuyuki Fujii, Naomi Osakabe
Summary: The study demonstrated that flavan 3-ol (FLs) may induce browning of adipose tissue in mice by activating the sympathetic nervous system (SNS), leading to increased expression of uncoupling protein (Ucp)-1 and thermogenic transcriptome factors. This effect was confirmed by a marked increase in urinary catecholamine (CA) levels, suggesting enhanced SNS activity.
Article
Food Science & Technology
Jaeyoon Byun, Seongsung Kwak, Jin-Hee Kwon, Minhee Shin, Dong-Kyu Lee, Chang-Hoon Rhee, Won-ho Kang, Jae-Wook Oh, Deu John M. Cruz
Summary: This study compared the pharmacodynamics of three BoNT/A formulations in mice and found that Coretox (R) provided a prolonged duration of action and significant paretic effects after repeated injections.
Article
Virology
Beatriz Pacin-Ruiz, Maria Francesca Cortese, David Tabernero, Sara Sopena, Josep Gregori, Selene Garcia-Garcia, Rosario Casillas, Adrian Najarro, Unai Aldama, Adriana Palom, Ariadna Rando-Segura, Anna Galan, Marta Vila, Mar Riveiro-Barciela, Josep Quer, Gloria Gonzalez-Aseguinolaza, Maria Buti, Francisco Rodriguez-Frias
Summary: This study used next-generation sequencing to analyze the ribozyme quasispecies of hepatitis delta virus (HDV). The ribozyme was found to be highly conserved overall, with a hyper-conserved region between nucleotides 715-745. Several mutations were observed, with the deletion of C64 showing a strong impact on HDV replication. The findings suggest that the conserved region of the ribozyme could be a potential target for gene-silencing strategies.
Review
Gastroenterology & Hepatology
Nerea Zabaleta, Laura Torella, Nicholas D. Weber, Gloria Gonzalez-Aseguinolaza
Summary: The efficient delivery of RNA molecules and the intentional modification of the host genome using nucleases have revolutionized modern medicine. Clinical trials have shown promising results in treating liver disorders and the breakout of CRISPR technology has marked a turning point in gene editing. In this review, preclinical data and different gene editing strategies for liver diseases are summarized.
Letter
Gastroenterology & Hepatology
Nicholas D. Weber, Javier Martinez-Garcia, Gloria Gonzalez-Aseguinolaza
JOURNAL OF HEPATOLOGY
(2022)
Article
Virology
Dawid Maciorowski, Cheikh Diop, Urja Bhatt, Reynette Estelien, Dan Li, Ruchi Chauhan, Luk H. Vandenberghe, Nerea Zabaleta
Summary: The SARS-CoV-2 pandemic has had a disastrous impact globally, with limitations in vaccine access due to logistical, economical, and sociological factors. Two AAV-based COVID-19 vaccines have shown promise in murine and primate models, but their effectiveness varies in obese and aged populations. Obesity does not significantly alter vaccine immunogenicity, but older mice have impaired vaccine response. These findings suggest that AAV-based vaccines may have limitations in older populations, while remaining applicable in obese and non-obese populations.
Review
Biochemistry & Molecular Biology
Javier Martinez-Garcia, Angie Molina, Gloria Gonzalez-Aseguinolaza, Nicholas D. Weber, Cristian Smerdou
Summary: Gene therapy shows promising results in treating cholestatic diseases, but challenges remain in translating this therapy to clinical practice and developing strategies for other types of cholestasis.
Review
Gastroenterology & Hepatology
Nerea Zabaleta, Carmen Unzu, Nicholas D. Weber, Gloria Gonzalez-Aseguinolaza
Summary: In this review, the authors discuss gene therapy involving the use of recombinant adeno-associated virus vectors for the treatment of inherited liver diseases, including ongoing clinical trials that are producing promising results. Clinical testing has revealed several key challenges associated with gene therapy, such as the interaction of the immune system with the vector and the risk of adverse events. The permanent modification of the host genome through gene editing raises concerns about oncogenicity and requires careful evaluation.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2023)
Article
Gastroenterology & Hepatology
Nicholas D. Weber, Leticia Odriozola, Irene Ros-Ganan, Guillermo Garcia-Porrero, David Salas, Josepmaria Argemi, Jean-Philippe Combal, Takashi K. Kishimoto, Gloria Gonzalez-Aseguinolaza
Summary: The study demonstrates that repeat administration of rAAV combined with immunotolerant nanoparticles can effectively treat PFIC3 in infant mice and reduce the risk of liver cancer.
Review
Biotechnology & Applied Microbiology
Helena Costa-Verdera, Carmen Unzu, Erika Valeri, Sahil Adriouch, Gloria Gonzalez Aseguinolaza, Federico Mingozzi, Anna Kajaste-Rudnitski
Summary: As the clinical experience in AAV vector-based gene therapies grows, there is a need to better understand and control the host immune responses. Our current understanding of the immune responses to AAV gene therapies is limited, which is further hindered by the lack of replication of clinical findings in preclinical animal models.
HUMAN GENE THERAPY
(2023)
Article
Cell Biology
Susana Aguilar, Paula Garcia-Olloqui, Lidia Amigo-Moran, Jose Luis Toran, Juan Antonio Lopez, Guillermo Albericio, Gloria Abizanda, Diego Herrero, Africa Vales, Saray Rodriguez-Diaz, Marina Higuera, Ruben Garcia-Martin, Jesus Vazquez, Carmen Mora, Gloria Gonzalez-Aseguinolaza, Felipe Prosper, Beatriz Pelacho, Antonio Bernad
Summary: Oxidative stress-induced myocardial apoptosis and necrosis play a critical role in ischemic infarction. This study identified and validated miR-935 as a highly differentially expressed miRNA in exosomes derived from human cardiac progenitor cells (CPC). Reduction of miR-935 expression promotes oxidative stress-associated apoptosis. Together with other exosomal miRNA members, miR-935 may counteract oxidative stress-related apoptosis in the CPC microenvironment.
Article
Pharmacology & Pharmacy
Andoni Gomez-Moreno, Enara San Sebastian, Jennifer Moya, Pilar Gomollon-Zueco, Sergio Isola, Africa Vales, Gloria Gonzalez-Aseguinolaza, Carmen Unzu, Urtzi Garaigorta
Summary: Gene therapy is a promising approach to treat inherited metabolic liver disorders. This study shows that using topoisomerase inhibitors can increase the expression of viral genes in non-dividing hepatic cells, with a greater effect seen in the integration-deficient LV strain. These effects are associated with increased DNA damage response.
Meeting Abstract
Biotechnology & Applied Microbiology
Laura Torella, Ibon Tamayo, Africa Vales, Daniel Moreno, Jessica Del Campo, Juan R. Rodriguez-Madoz, Mikel Hernaez, Eduardo Salido, Gloria Gonzalez-Aseguinolaza, Nerea Zabaleta
Meeting Abstract
Biotechnology & Applied Microbiology
Nerea Zabaleta, Urja Bhatt, Cecile Herate, Pauline Maisonnasse, Jessica A. Chichester, Julio Sanmiguel, Cheikh Diop, James M. Wilson, Roger Le Grand, Luk H. Vandenberghe
Meeting Abstract
Biotechnology & Applied Microbiology
Eric M. Zinn, Pauline Schmit, Cheikh Diop, Allegra Fieldsend, Ru Xiao, Nerea Zabaleta, Luk H. Vandenberghe
Article
Immunology
Irene Ros-Ganan, Mirja Hommel, Laia Trigueros-Motos, Blanche Tamarit, Estefania Rodriguez-Garcia, David Salas, Guiomar Perez, Anne Douar, Jean Philippe Combal, Bernard Benichou, Veronica Ferrer, Gloria Gonzalez-Aseguinolaza
Summary: This study tested the effectiveness of an enzyme called IdeS in cleaving neutralizing antibodies and improving the transduction efficiency of AAV-mediated gene therapy. The results showed that IdeS was able to efficiently cleave human IgG and had varying effects on different AAV serotypes in vivo. The study suggests that preconditioning with IdeS could provide a unique treatment opportunity for patients who are excluded from gene therapy due to elevated levels of anti-AAV antibodies.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2022)