Article
Environmental Sciences
Lingli Chen, Hongmei Ning, Penghuan Jia, Hongli Zhang, Yuye Liu, Rui Wang, Fei Ren, Zhihong Yin, Dongfang Hu, Yaming Ge
Summary: Excessive fluoride intake can lead to health risks, including damage to the cytoskeleton and synapses, which affects the intellectual development of humans and animals. In this study, the researchers investigated the role of the RhoA/ROCK signalling pathway in fluoride-induced cytoskeletal injury and synaptic dysfunction. They found that inhibiting RhoA/ROCK activation could alleviate the damaging effects of fluoride on the cytoskeleton and synapses, and improve cognitive impairment. These findings suggest that fasudil and Y-27632 can reverse the neurotoxicity caused by fluoride exposure.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Article
Dermatology
Hai Wang, Fang Fang, Shaofeng Chen, Xing Jing, Yuehong Zhuang, Yun Xie
Summary: This study evaluated the efficacy of Fasudil in promoting flap survival and reinnervation. The results showed that Fasudil significantly reduced the necrosis rate of the flaps, increased the diameter of the iliolumbar artery, improved blood perfusion and microvascular density of the flaps. Additionally, Fasudil promoted axon growth.
INTERNATIONAL WOUND JOURNAL
(2022)
Review
Neurosciences
Abhishek Roy, Zarna Pathak, Hemant Kumar
Summary: The difficulties in regenerating after CNS injuries, including spinal cord injury, are attributed to factors such as hypertrophic scarring, inhibitory molecules, and the absence of mechanisms responsible for axonal regeneration in the adult CNS. Strategies to improve axon regeneration include neutralizing inhibitors/proteins and stabilizing microtubules. Furthermore, the focus on counteracting inhibitors of axonal growth and their downstream signaling through the RhoA/ROCK pathway is emphasized.
EXPERIMENTAL NEUROLOGY
(2021)
Review
Neurosciences
Weizhuo Lu, Jiyue Wen
Summary: Ischemic stroke is a major cause of disability and death, and enhancing axonal regeneration and remyelination can promote neural functional recovery. However, the activation of the RhoA/ROCK pathway plays a harmful role in axonal recovery and regeneration. Inhibition of this pathway can promote axonal regeneration and remyelination. Additionally, hydrogen sulfide (H2S) has a significant neuroprotective role in the recovery from ischemic stroke. This review discusses the relationship among H2S, the RhoA/ROCK pathway, astrocytes, and microglial cells in axonal remyelination following ischemic stroke, aiming to reveal new strategies for prevention and treatment of this devastating disease.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Pingping Liu, Zhenghui Xiao, Xiulan Lu, Xinping Zhang, Jiaotian Huang, Cheng Li
Summary: The combination of fasudil and SR1001 has a synergistic effect on protecting against sepsis-associated pancreatic injury, reducing Th17 cell differentiation and IL-17 expression, and inhibiting the expressions of GEF-H1, RhoA, and ROCK1. Moreover, the combination treatment also reduces apoptosis of pancreatic cells.
Article
Biochemistry & Molecular Biology
Claudia M. Lucero, Lucas Marambio-Ruiz, Javiera Balmazabal, Juan Prieto-Villalobos, Marcelo Leon, Paola Fernandez, Juan A. Orellana, Victoria Velarde, Juan C. Saez, Gonzalo Gomez
Summary: This study found that the activation of Cx43 hemichannels and inhibition of cell-cell coupling during inflammation may contribute to oxidative stress and damage of mesangial cells through the RhoA/ROCK pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Toxicology
Xiwen Ren, Tong Meng, Xingbin Ren, Xiaoyu Li, Lin Lu
Summary: Fasudil attenuates APAP-induced liver injury by targeting Rhoa/ROCK signal pathway, inhibiting inflammation and oxidative damage in liver tissue.
JOURNAL OF TOXICOLOGICAL SCIENCES
(2021)
Article
Physiology
Fen Tang, Kongqian Huang, Biyan Peng, Wen Deng, Ning Su, Fan Xu, Mingyuan Zhang, Haibin Zhong
Summary: The study aimed to evaluate the effect of the RhoA/ROCK inhibitor Fasudil on retinal neovascularization in vivo and angiogenesis in vitro. The researchers found that RhoA/ROCK expression was upregulated in the OIR model, and Fasudil effectively reduced retinal neovascularization and inhibited angiogenesis. These results suggest that Fasudil may be a potential treatment strategy for retinal vascular diseases.
JOURNAL OF VASCULAR RESEARCH
(2023)
Review
Pharmacology & Pharmacy
Emily Holz, Martine Darwish, Devin B. Tesar, Whitney Shatz-Binder
Summary: In the last few decades, the complexity of therapeutic molecular entities has been continuously evolving in the pharmaceutical industry to meet the needs of novel diseases and delivery challenges. One area of interest is the development of chemically enhanced peptide and protein therapeutics. This review evaluates the development landscape of protein-based chemical conjugates, focusing on considerations such as pharmacokinetics modulation, safety, and entry into difficult targets, as well as bioavailability. The breadth of novel peptide- or protein-based therapeutics supports the pursuit of more complex therapeutic strategies.
Article
Biochemistry & Molecular Biology
Pablo Bonilla, Joaquim Hernandez, Esther Giraldo, Miguel A. Gonzalez-Perez, Ana Alastrue-Agudo, Hoda Elkhenany, Maria J. Vicent, Xavier Navarro, Michael Edel, Victoria Moreno-Manzano
Summary: The combination of PA-C with stem cell transplantation has been shown to protect neural stem cells in vitro, significantly reduce scar formation, promote preservation of neurons and axons, and inhibit inflammatory response in microglia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Materials Science, Multidisciplinary
Tianhui Zhang, Feng Lin, Wanguo Liu, Yixuan Liu, Zhihui Guo, Chunsheng Xiao, Xiuli Zhuang, Xuesi Chen
Summary: This study presents a novel lipid-polymer nanoparticle PELPNPs, which effectively scavenges ROS and reduces long-term secondary injury in a rat SCI model. PELPNPs show promise for effective treatment of clinical SCI by protecting neurons and myelin sheaths through ROS scavenging and anti-inflammatory abilities.
APPLIED MATERIALS TODAY
(2021)
Review
Neurosciences
Areez Shafqat, Ibrahem Albalkhi, Hamzah M. Magableh, Tariq Saleh, Khaled Alkattan, Ahmed Yaqinuddin
Summary: Poor axonal regeneration and functional recovery after SCI is not primarily due to the injury scar, but rather a failure to stimulate axon growth adequately. Targeting neuroinflammation and glial scarring may not be as effective as neuron-directed approaches. This raises questions about the viability of these translational avenues.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Neurosciences
Andrea J. Mothe, Peer B. Jacobson, Mitchell Caprelli, Antigona Ulndreaj, Radmehr Rahemipour, Lili Huang, Philippe P. Monnier, Michael G. Fehlings, Charles H. Tator
Summary: RGMa plays an important role in spinal cord injury, and delayed administration of elezanumab promotes neuroprotection and regeneration, with efficacy demonstrated in a cervical SCI model. Elezanumab facilitates recovery of motor and fine motor function, and improves specific gait parameters.
NEUROBIOLOGY OF DISEASE
(2022)
Review
Instruments & Instrumentation
Snezana Dordevic, Maria Medel Gonzalez, Inmaculada Conejos-Sanchez, Barbara Carreira, Sabina Pozzi, Rita C. Acurcio, Ronit Satchi-Fainaro, Helena F. Florindo, Maria J. Vicent
Summary: The field of nanomedicine faces challenges in regulatory clarity and consistency. Developing nanomedicines requires considerations of critical quality attributes, appropriate analytical methods, important process parameters, and pre-clinical models. Close collaboration with regulatory agencies is advised to accelerate the development of future nanomedicines.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2022)
Article
Cell Biology
Maria Jose Lopez-Grueso, Carmen Alicia Padilla, Jose Antonio Barcena, Raquel Requejo-Aguilar
Summary: The multifunctional protein DJ-1 is involved in the development of Parkinson's disease through disruption of cell cycle checkpoints. It leads to accumulation of p-tau and alpha-synuclein proteins, alteration of PI3K/AKT and MAPK signaling pathways, and deregulation of Cdk5. The findings suggest that aborted cell cycle re-entry could be the trigger for DJ-1-associated Parkinson's disease, and targeting cell cycle re-entry may improve therapeutic strategies.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2022)
Article
Engineering, Biomedical
Yolanda Fernandez, Julie Movellan, Laia Foradada, Vanessa Gimenez, Natalia Garcia-Aranda, Sandra Mancilla, Ana Arminan, Sven Even Borgos, Astrid Hyldbakk, Anna Bogdanska, Oliviero L. Gobbo, Adriele Prina-Mello, Jessica Ponti, Luigi Calzolai, Oleksandr Zagorodko, Elena Gallon, Amaya Nino-Pariente, Alison Paul, Simo Schwartz Jr, Ibane Abasolo, Maria J. Vicent
Summary: The study demonstrates that tert-Ser-PTX conjugate can provide sustained release of PTX in a pH-responsive manner over 2 weeks, along with epimerization of PTX to 7-epi-PTX. Serum proteins can stabilize tert-Ser-PTX, showing enhanced stability in human serum compared to PBS. While in vitro efficacy assessments in PCa cells showed IC50 values higher than the free form of PTX, in vivo tolerability assays revealed that tert-Ser-PTX significantly reduces systemic toxicities associated with free PTX treatment.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Cell Biology
Esther Giraldo, Pablo Bonilla, Mara Mellado, Pablo Garcia-Manau, Carlota Rodo, Ana Alastrue, Eric Lopez, Elena Carreras Moratonas, Ferran Pellise, Snezana Dordevic, Maria J. Vicent, Victoria Moreno Manzano
Summary: Neural precursor cell transplantation is a promising therapy for spinal cord injuries, but its clinical translation remains challenging. A study found that priming human-fetal-spinal-cord-derived NPCs with PGA-SS-FAS improved neuronal differentiation and enhanced migration and survival of transplanted cells in the spinal cord.
Review
Cell Biology
Raquel Requejo-Aguilar
Summary: Neurodegenerative diseases are caused by the progressive loss of specific neurons. The exact mechanisms of action of these diseases are unknown, but aberrant cell cycle re-entry seems to play a major role. Factors such as oxidative stress, DNA damage response, signaling pathway disturbance, and ubiquitin proteasome malfunction contribute to cell cycle re-entry in post-mitotic neurons, with Cdk5 being a key protein involved.
NEURAL REGENERATION RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Tetiana Melnyk, Esther Masia, Oleksandr Zagorodko, Inmaculada Conejos-Sanchez, Maria J. Vicent
Summary: Brain tumors, specifically malignant gliomas, are a major cause of pediatric cancer death. In this study, we synthesized a family of polyglutamate-palbociclib conjugates to overcome limitations associated with free palbociclib in the treatment of pediatric brain tumors. We evaluated the activity of these conjugates in different types of brain tumor cells and discovered that the microenvironment and conformational changes influenced drug release kinetics and therapeutic output.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Biochemistry & Molecular Biology
Daniel J. Lagal, Maria J. Lopez-Grueso, Jose R. Pedrajas, Thomas L. Leto, J. Antonio Barcena, Raquel Requejo-Aguilar, C. Alicia Padilla
Summary: PRDX6, a member of the peroxiredoxin family, exhibits peroxidase, phospholipase A2 (PLA2), and lysophosphatidylcholine (LPC) acyltransferase (LPCAT) activities. Knockout of PRDX6 in SNU475 hepatocarcinoma cells leads to lipid peroxidation, mitochondrial dysfunction, metabolic reprogramming, altered cytoskeleton, and down-regulation of growth-related proteins. Activation of upstream regulators and inhibition of migration and invasiveness suggest the involvement of PRDX6 in tumor development and metastasis.
Article
Chemistry, Analytical
Ines Domingo-Orti, Patricia Ferrer-Torres, Ana Arminan, Maria J. Vicent, Antonio Pineda-Lucena, Martina Palomino-Schaetzlein
Summary: Studying metabolism can help understand the relationship between mitochondrial activity and various diseases. This study developed a method to characterize mitochondrial metabolism in healthy, tumoral, and metastatic tissues and discovered significant differences in metabolites between these tissues.
ANALYTICAL CHEMISTRY
(2023)
Article
Engineering, Biomedical
Sonia Vicente-Ruiz, Ana Arminan, Katia Maso, Elena Gallon, Oleksandr Zagorodko, Julie Movellan, Fernanda Rodriguez-Otormin, Maike Baues, Jan-Niklas May, Federica De Lorenzi, Twan Lammers, Maria J. Vicent
Summary: Modifying biological agents with polymers such as PEG has clinical benefits, but PEGylated derivatives have toxicity issues, which leads to the search for alternatives. Conjugating PGA to AVE1642 alters its bio-nano interface and anti-tumor activity, inhibiting IGF-1R internalization and altering cell trafficking. PGA conjugation enhances AVE1642's anti-tumor activity and inhibits PI3K and MAPK signaling more effectively than AVE1642 alone.
Article
Chemistry, Multidisciplinary
Snezana Dordevic, Maria Medel, Justine Hillaert, Esther Masia, Inmaculada Conejos-Sanchez, Maria J. Vicent
Summary: The design of a suitable linking moiety is crucial for controlled drug release in polymer-drug conjugates. This study evaluates the influence of drug and spacer chemical structures on drug release and the biological effects of the resultant PDCs. A comprehensive characterization method is developed to quantify low drug concentrations and elucidate metabolite presence. The study provides insights into how drug structural features affect drug release and highlights the importance of rigorous linker characterization in understanding structure-function correlations.
Article
Engineering, Biomedical
Javier Monreal-Trigo, Jose Manuel Terres-Haro, Beatriz Martinez-Rojas, Maria del Mar Sanchez-Martin, Esther Giraldo, Victoria Moreno Manzano, Miguel Alcaniz Fillol
Summary: Optogenetics is a versatile field in neuroscience that has applications in studying neuronal pathways and treating various disorders. However, current instrumentation cannot observe certain phenomena, leading researchers to develop a controllable optogenetic stimulation matrix through a graphical user interface, which was validated in experiments.
IEEE TRANSACTIONS ON BIOMEDICAL CIRCUITS AND SYSTEMS
(2022)
Article
Oncology
Anni Lepland, Alessio Malfanti, Uku Haljasorg, Eliana K. Asciutto, Monica Pickholz, Mauro Bringas, Snezana Dordevic, Liis Salumae, Paert Peterson, Tambet Teesalu, Maria J. Vicent, Pablo Scodeller
Summary: This study developed a novel TAM-depleting agent and demonstrated its efficacy in a triple-negative breast cancer mouse model. The agent specifically targets CD206+ TAMs and does not show acute liver or kidney toxicity in vivo. Treatment with this agent showed potential benefits in reducing tumor progression and modulating the immune system. This research represents a novel design of a peptide-targeted nanotherapeutic for TAM depletion.
CANCER RESEARCH COMMUNICATIONS
(2022)
Article
Engineering, Biomedical
Lin-Lin Luo, Jie Xu, Bing-Qiao Wang, Chen Chen, Xi Chen, Qiu-Mei Hu, Yu-Qiu Wang, Wan-Yun Zhang, Wan-Xiang Jiang, Xin-Ting Li, Hu Zhou, Xiao Xiao, Kai Zhao, Sen Lin
Summary: A novel AAV serotype, AAVYC5, introduced in this study, showed more efficient transduction into multiple retinal layers compared to AAV2, and enabled successful delivery of anti-angiogenic molecules in mice and non-human primates.