Review
Biochemistry & Molecular Biology
Arpad Szallasi
Summary: Today's sedentary lifestyle and poor dietary habits contribute to the increasing prevalence of hypertension, a major risk factor for stroke. Recent research suggests that the activation of TRPV1 receptor by capsaicin, a compound found in chili peppers, can lower blood pressure and potentially be a therapeutic target for hypertensive patients. However, the mechanism of action of capsaicin on blood pressure regulation is more complex than previously understood. Further studies are needed to explore the potential benefits of TRPV1-targeting drugs in treating hypertension.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Jin Mi Kang, Sun Ok Kwon, Jihyae Ann, Sunho Lee, Changhoon Kim, Nayeon Do, Jin Ju Jeong, Peter M. Blumberg, Heejin Ha, Thi Ngoc Lan Vu, Sanghee Yoon, Sun Choi, Robert Frank-Foltyn, Bernhard Lesch, Gregor Bahrenberg, Hannelore Stockhausen, Thomas Christoph, Jeewoo Lee
Summary: The series of 117 2-(halogenated phenyl) acetamide and propanamide analogs were investigated as TRPV1 antagonists, with halogenated phenyl A-region analogs showing a broad functional profile. Antagonists 28 and 92 exhibited potent antagonism against capsaicin for hTRPV1, with antagonist 92 displaying promising analgesic activity in vivo. Molecular modeling of compound 92 suggested that the two fluoro groups in the A-region interacted hydrophobically with the receptor.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Tatsuya Kida, Nobuaki Takahashi, Masayuki X. Mori, Jiacheng H. Sun, Hideto Oota, Kosuke Nishino, Takashi Okauchi, Yuta Ochi, Daisuke Kano, Ukihide Tateishi, Yasuyoshi Watanabe, Yilong Cui, Yasuo Mori, Hisashi Doi
Summary: TRPV1-targeted compounds were synthesized by modifying the structure of SB366791, and higher antagonistic activities were achieved by avoiding amide-iminol tautomerization. Additionally, explorative PET imaging trials were conducted using labeled derivatives, providing a basis for further applications.
RSC MEDICINAL CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Koki Nagaoka, Takuya Nagashima, Nozomi Asaoka, Hiroki Yamamoto, Chihiro Toda, Gen Kayanuma, Soni Siswanto, Yasuhiro Funahashi, Keisuke Kuroda, Kozo Kaibuchi, Yasuo Mori, Kazuki Nagayasu, Hisashi Shirakawa, Shuji Kaneko
Summary: It was discovered that acetaminophen was able to prevent adverse movement symptoms induced by antipsychotic drugs, and this effect was achieved by activating TRPV1 channels to increase the activity of indirect pathway neurons.
Article
Medicine, Research & Experimental
Ben Katz, Rachel Zaguri, Simon Edvardson, Channa Maayan, Orly Elpeleg, Shaya Lev, Elyad Davidson, Maximilian Peters, Shlomit Kfir-Erenfeld, Esther Berger, Shifa Ghazalin, Alexander M. Binshtok, Baruch Minke
Summary: This study provides direct evidence in humans for pain-related functional changes linked to TRPV1, a potential target in the development of pain relievers. Two individuals carrying a homozygous missense mutation in TRPV1 demonstrated insensitivity to heat stimulation, elevated pain thresholds, and abnormal responses to a TRPA1 channel activator. These findings highlight the importance of TRPV1 in pain modulation and may contribute to the development of novel pain therapies.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Multidisciplinary Sciences
Tina Blazevic, Cosmin I. Ciotu, Markus Gold-Binder, Elke H. Heiss, Michael J. M. Fischer, Verena M. Dirsch
Summary: Capsaicin, an active compound of chili peppers, can inhibit platelet-derived growth factor-induced proliferation in primary rat vascular smooth muscle cells (VSMCs), possibly through a role of TRPV1. However, commercially available antibodies were ineffective in detecting TRPV1 expression. Moreover, TRPV1 agonists did not increase intracellular calcium levels in VSMCs. RT-qPCR results showed low TRPV1 expression in VSMCs, suggesting the absence of canonical TRPV1 channel activity.
Article
Pharmacology & Pharmacy
Ankush M. Korishettar, Yoshinori Nishijima, Zhihao Wang, Yangjing Xie, Juan Fang, David A. Wilcox, David X. Zhang
Summary: TRPV1 channels are expressed in the human vasculature and affect vascular tone of human arterioles when activated. Their vasomotor function is modulated by endothelin-1, partly mediated by protein kinase C.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jing Hu, Mengkang Gao, Yang Zhang, Yusui Wang, Zhenrui Qiao, Weiya Zhang, Qiang Wang, Lin Yan, Hai Qian
Summary: In this study, three series of new piperazine urea TRPV1 antagonists were designed, synthesized, and evaluated, among which compound 5ac showed excellent TRPV1 antagonistic activity, good bioavailability, and no hyperthermia side effects. The molecular docking study revealed that compound 5ac interacted well with the amino acid residues on rTRPV1 through hydrophobic interaction, making it an efficient TRPV1 antagonist and a potential candidate for analgesic drug development.
BIOORGANIC CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Fang Zhao, Shuangyan Wang, Yan Li, Jin Wang, Yujing Wang, Chunlei Zhang, Yong Li, Longjiang Huang, Ye Yu, Jie Zheng, Boyang Yu, Isaac N. Pessah, Zhengyu Cao
Summary: CMEA directly activates TRPV1 channels to produce eye irritation, with selective ablation of TRPV1 channels ameliorating the eye irritation caused by CMEA. Rodents exhibit stronger responses to CMEA than rabbits, indicating that rabbits are poor models for evaluating human eye irritants structurally related to CMEA.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Review
Cell Biology
Yixiao Xu, Yongcai Zhao, Binghong Gao
Summary: TRPV1 channel plays a role in releasing Ca2+ from cells under high-temperature stress, thus enhancing mitochondrial biogenesis in skeletal muscle. High-temperature stress can benefit the adaptation of muscle mitochondria to aerobic capacity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Ye Liu, Ruizheng Zhu, Bei Liu, Wuqing Wang, Ping Yang, Zhonglian Cao, Xiaolei Yang, Wandi Du, Qing Yang, Jingru Liang, Jiarong Hu, Guo Ma
Summary: This study aimed to disclose the antidiabetic mechanisms of Rehmanniae Radix. The results showed that Rehmanniae Radix displayed an inspiring antidiabetic effect by reducing fasting blood glucose and insulin resistance, upregulating the mRNA and protein expressions of TRPV1, and downregulating mRNA expression of SCD1.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Liping Liu, Xiaodong Sun, Yunliang Guo, Keli Ge
Summary: Evodiamine (EVO) from Evodiae fructus has antitumor effects on gastric cancer cells, mainly through cytotoxicity, including inhibition of proliferation, cell cycle arrest, apoptosis, and metastasis. This study aimed to investigate the role of TRPV1/Ca2+ in EVO-induced cytotoxicity in human gastric cancer cells. The results showed that EVO exposure led to ROS generation and apoptotic cell death, which could be ameliorated by pretreatment with EUK134. EVO exposure also induced ROS generation and mitochondrial dysfunction, mainly through mitochondrial ROS generation, which could be attenuated by rotenone pretreatment. Moreover, EVO-induced cytotoxicity could be significantly ameliorated by chelation of intracellular Ca2+, confirming that EVO induces cell death through Ca2+ overload. Inhibition of TRPV1 attenuated Ca2+ influx, ROS generation, and apoptotic cell death induced by EVO exposure, while overexpression of TRPV1 augmented EVO-induced cytotoxicity. Furthermore, inhibition of mitochondrial calcium uniporter (MCU) attenuated EVO-induced cell death and mitochondrial dysfunction. EVO exposure also induced endoplasmic reticulum stress, which was depleted by EUK134 pretreatment.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Immunology
Yuchen Cai, Jin Chen, Hao Sun, Tianyi Zhou, Xueyao Cai, Yao Fu
Summary: In this study, the upregulation of TRPV1 in FECD was observed, and its association with immune regulation was investigated. Negative correlation between TRPV1 and various immune cells, especially Tregs, was found. TRPV1-related core genes and immune-related pathways were identified, providing new insights for the mechanistic and therapeutic studies of FECD.
CLINICAL IMMUNOLOGY
(2023)
Article
Chemistry, Medicinal
Yue Qiao, Yang Zhang, Zhenrui Qiao, Wenya He, Yingda Chen, Depu Song, Guohao Wang, Ning Guo, Lulian Shao, Zhiyong Tian, Qiang Wang, Lin Yan, Hai Qian
Summary: In this study, novel molecules based on the key pharmacophore structures of classic TRPV1 ligands were designed and synthesized, and a potent TRPV1 antagonist with excellent central nervous system penetration and bioavailability was identified. The findings provide a valuable lead for the development of novel TRPV1 antagonists.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Katherine Sattler, Ibrahim El-Battrawy, Lukas Cyganek, Siegfried Lang, Huan Lan, Xin Li, Zhihan Zhao, Jochen Utikal, Thomas Wieland, Martin Borggrefe, Xiaobo Zhou, Ibrahim Akin
Summary: Recent evidence shows the important role of the TRPV1 channel in the cardiovascular system and its association with inflammation. Experimental results demonstrate that TRPV1 mediates LPS-induced inflammation in cardiomyocytes, leading to changes in cellular electrophysiology. Further studies are needed to investigate the underlying pathways and clinical applications of these findings.
SCIENTIFIC REPORTS
(2021)
Article
Clinical Neurology
Bjoern B. Hofmann, Christian Rubbert, Bernd Turowski, Daniel Haenggi, Sajjad Muhammad
Summary: For extremely rare bilateral distal fusiform superior cerebellar artery (SCA) aneurysms, surgical therapy reaches its limit, but mini-flow diverter devices (FDDs) offer an effective and successful alternative treatment option.
JOURNAL OF NEUROLOGICAL SURGERY PART A-CENTRAL EUROPEAN NEUROSURGERY
(2023)
Article
Chemistry, Physical
Jose Luis Velazquez-Libera, Julio Caballero, Jans Alzate-Morales, J. Javier Ruiz-Pernia, Inaki Tunon
Summary: We conducted a computational study on the reaction mechanism of USP7 with Ubiquitin-Rhodamine 110-G substrate using a robust methodology. Our findings provide insights into the dynamic nature of USP7 enzyme-substrate complexes and describe the conformational changes observed in our simulations. The protein-protein interactions and geometric states identified in this study could be utilized for designing potent and selective inhibitors for USP7's activity.
Article
Critical Care Medicine
Bjoern B. Hofmann, Daniel M. Donaldson, Igor Fischer, Cihat Karadag, Milad Neyazi, Guilherme S. Piedade, Yousef Abusabha, Sajjad Muhammad, Christian Rubbert, Daniel Haenggi, Kerim Beseoglu
Summary: This study aimed to investigate the influence of blood pressure on early computed tomography perfusion (CTP) imaging in patients with aneurysmatic subarachnoid hemorrhage (aSAH). The results showed an inverse correlation between mean arterial pressure (MAP) and mean transit time (MTT) in early CTP imaging. Lower blood pressure was associated with longer MTT, and this correlation became stronger with the severity of aSAH. Therefore, maintaining physiological blood pressure values in the early phase of aSAH is crucial.
NEUROCRITICAL CARE
(2023)
Letter
Critical Care Medicine
Bjoern B. Hofmann, Christian Rubbert, Kerim Beseoglu
NEUROCRITICAL CARE
(2023)
Article
Oncology
Elizabeth Orozco-Garcia, D. J. van Meurs, JC. Calderon, Raul Narvaez-Sanchez, M. C. Harmsen
Summary: Vascularization is a crucial process for cell and tissue survival, and its alterations play a significant role in the development and progression of various diseases. PTEN and Hippo signaling are key players in vascular system development and homeostasis, and their suppression is associated with developmental defects and cancer. Non-coding RNAs (ncRNAs) are regulators of PTEN and Hippo pathways during development and disease. This paper reviews the mechanisms by which exosome-derived ncRNAs modulate endothelial cell plasticity during physiological and pathological angiogenesis, providing insights into cellular communication during tumoral and regenerative vascularization.
TRANSLATIONAL ONCOLOGY
(2023)
Article
Cell & Tissue Engineering
Kaixuan Yan, Jiaxing Zheng, Mark Andreas Kluth, Lin Li, Christoph Ganss, Benito Yard, Richard Magdeburg, Markus H. H. Frank, Prama Pallavi, Michael Keese
Summary: ABCB5(+) MSCs therapy can restore cellular Ca2+ homeostasis, which may beneficially affect the angiogenic function of endothelial cells under hypoxia in vitro and in vivo.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Chemistry, Multidisciplinary
S. Monroy-Moya, J. Caballero, F. Gonzalez-Norambuena, M. Simirgiotis, E. Sanchez, C. Areche, D. Fuentealba, A. Cornejo
Summary: Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide, and the treatment focuses on delivering L-DOPA. In this study, multiple compounds including flavonols, isoflavone, flavone, and compounds with alpha, beta unsaturated carbonyl moieties were found to inhibit alpha-synuclein fibrillization and promote cell proliferation and differentiation.
Article
Neurosciences
Bjoern B. Hofmann, Igor Fischer, Daniel M. Donaldson, Yousef Abusabha, Cihat Karadag, Sajjad Muhammad, Kerim Beseoglu, Daniel Haenggi, Bernd Turowski, Christian Rubbert, Jan F. Cornelius, Marcel A. Kamp
Summary: The concept of early brain injury (EBI) assumes a decrease in brain perfusion after aneurysmal subarachnoid hemorrhage (aSAH). This study investigated whether the heterogeneity of computed tomography perfusion (CTP) imaging in the EBI phase is an independent predictor of the neurological outcome after aSAH. The analysis found that microvascular perfusion heterogeneity, assessed by the heterogeneity of mean transit time (MTT) in early CTP imaging, does not appear to be an independent predictor of the neurological outcome 6 months after aSAH.
Review
Biotechnology & Applied Microbiology
Linda Vriend, Berend van der Lei, Martin C. C. Harmsen, Joris A. A. van Dongen
Summary: In recent years, adipose tissue transplantation has emerged as a crucial treatment for tissue restoration and regeneration. The regenerative properties of adipose tissue, attributed to its stromal vascular fraction (tSVF), have been shown to reduce scarring and accelerate wound healing. This review focuses on dermal regeneration using adipose-tissue components such as adipose-tissue-derived stromal cells (ASCs), their secreted trophic factors, and the extracellular matrix (ECM). The potential of using an ECM-based hydrogel loaded with trophic factors to enhance wound healing is also explored as an alternative to traditional adipose tissue transplantation.
BIOENGINEERING-BASEL
(2023)
Article
Biochemistry & Molecular Biology
Hector Montecino-Garrido, Magdalena Sepulveda, Diego Mendez, Matias Monroy-Cardenas, Sergio Alfaro, Mariela Gonzalez-Avendano, Julio Caballero, Felix A. Urra, Ramiro Araya-Maturana, Eduardo Fuentes
Summary: In this study, the effects of triphenylphosphonium-linked acyl hydroquinone derivatives with different alkyl chain lengths on the metabolism and function of human platelets were evaluated. It was found that longer alkyl chain lengths were associated with increased cytotoxicity and decreased mitochondrial membrane potential. Molecular dynamics simulations indicated that the permeability of the mitochondrial membrane may be involved in the cytotoxicity of phosphonium salts. These findings are important for the design of new TPP+-based drugs with a safe cardiovascular profile.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Ricelia Gonzalez, Juliana Murillo-Lopez, Walter Rabanal-Leon, Luis Prent-Penaloza, Odette Concepcion, Pedro Olivares, Yorley Duarte, Alexander F. de la Torre, Margarita Gutierrez, Julio Caballero
Summary: Novel alpha, beta-unsaturated carbonyl depsipeptides and peptoids incorporating various chromophores were synthesized using multicomponent reactions. UV/Vis spectroscopy was used to study the photophysical properties of the compounds, and the differences in electron delocalization caused by different chromophores were captured in the spectra. A photostability study for one compound showed that its molecular structure remained unchanged after exposure to UV radiation. Fluorescence analysis revealed incipient emission and blue fluorescence for specific compounds under UV radiation. The photophysical properties and electronic structure were also studied theoretically.
FRONTIERS IN CHEMISTRY
(2023)
Review
Biotechnology & Applied Microbiology
Jan Aart M. Schipper, Constance J. H. C. M. van Laarhoven, Rutger H. Schepers, A. Jorien Tuin, Marco C. Harmsen, Fred K. L. Spijkervet, Johan Jansma, Joris A. van Dongen
Summary: Clinical indications for adipose tissue therapy are expanding towards a regenerative-based approach. Mechanical fractionation procedures are effective in obtaining tissue stromal vascular fraction (tSVF) for therapeutic purposes such as skin rejuvenation, wound healing, and osteoarthritis. Centrifugation prior to mechanical fractionation seems to be the most effective method.
BIOENGINEERING-BASEL
(2023)
Article
Cell & Tissue Engineering
Erika Pinheiro-Machado, Vasilena E. Getova, Martin C. Harmsen, Janette K. Burgess, Alexandra M. Smink
Summary: The secretome of adipose-derived stromal cells (ASC) is a heterogeneous mixture of components that have a beneficial influence on cellular microenvironments. Pathophysiological conditions can enhance the therapeutic capacity of ASC and the benefits of their secretome. Secretomics, the unbiased analysis of a cell secretome by mass spectrometry, is a powerful tool to understand the composition of ASC secretomes. However, the currently available ASC secretomic studies lack standardization, making it difficult to draw solid conclusions on the therapeutic value of different ASC secretomes.
STEM CELL REVIEWS AND REPORTS
(2023)
Article
Respiratory System
Dennis Kruk, Anna C. Y. Yeung, Alen Faiz, Nick H. T. ten Hacken, Wim Timens, Toin H. van Kuppevelt, Willeke Daamen, Danique Hof, Martin C. Harmsen, Mauricio Rojas, Irene H. Heijink
Summary: This study evaluated the transcriptome differences between lung-derived MSCs (LMSCs), bone marrow-derived MSCs (BM-MSC), and adipose-derived MSCs (AD-MSCs) from COPD patients and non-COPD controls. The results showed strong gene signature differences between MSCs from different sources. LMSCs predominantly expressed FGF10 and HGF growth factors. MSCs from all sources displayed altered gene expression in COPD, with the most significant changes observed in AD-MSCs, particularly in genes involved in extracellular matrix binding and expression. The gene CSGALNACT1 showed the strongest difference between COPD and control in LMSCs, which is a gene involved in extracellular matrix modulation.
RESPIRATORY RESEARCH
(2023)
Article
Engineering, Biomedical
Meng Zhang, Fenghua Zhao, Xue Zhang, Linda A. Brouwer, Janette K. Burgess, Martin C. Harmsen
Summary: This study found that MRC-5 fibroblasts promote collagen fiber remodeling and deposition of fibronectin in the hydrogel, leading to modifications in the ECM microenvironment and promoting vascularization.
MATERIALS TODAY BIO
(2023)
