Article
Biochemistry & Molecular Biology
Volker Herzig, Yong-Cyuan Chen, Yanni K-Y Chin, Zoltan Dekan, Yu-Wang Chang, Hui-Ming Yu, Paul F. Alewood, Chien-Chang Chen, Glenn F. King
Summary: This study identified a tarantula venom from Avicularia spec. that can inhibit specific subtypes of T-type calcium channels, with the active toxin being omega-Avsp1a. The research suggests that omega-Avsp1a can inhibit specific subtypes of T-type calcium channels, and the domain-1 of Ca(V)3.3 is crucial for this inhibitory effect.
Article
Oncology
Hiroyuki Inoue, Atsushi Shiozaki, Toshiyuki Kosuga, Hiroki Shimizu, Michihiro Kudou, Takuma Ohashi, Tomohiro Arita, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Mitsuo Kishimoto, Eiichi Konishi, Eigo Otsuji
Summary: CACNA2D1 regulates the apoptosis signaling pathway, serving as a potential biomarker for cancer growth and therapeutic target for gastric cancer. Knocking down CACNA2D1 in the experiment suppressed cell proliferation, migration, and invasion, while inducing apoptosis. High expression levels of CACNA2D1 were identified as an independent poor prognostic factor in GC patients.
ANNALS OF SURGICAL ONCOLOGY
(2022)
Article
Ophthalmology
Yuto Tei, Yoshinori Mikami, Masanori Ito, Taichiro Tomida, Daisuke Ohshima, Yuichi Hori, Satomi Adachi-Akahane
Summary: The pathogenic mechanism of dry eye-induced chronic pain in the anterior eye area was explored in a rat dry eye model. The study found that hypersensitivity and hyperalgesia were caused by central sensitization in the trigeminal nucleus with upregulation of the alpha(2)delta-1 subunit. Chronic treatment with pregabalin effectively alleviated the pain symptoms and normalized neural activity and astrocyte activation.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Merav Mor, Ofer Beharier, David Cook, Craig R. Campbell, Levi A. Gheber, Amos Katz, Arie Moran, Yoram Etzion
Summary: ZnT1 is a zinc transporter that plays a crucial role in maintaining cellular zinc balance. In addition to its role in zinc transport, ZnT1 also inhibits the L-type calcium channel (LTCC) and activates the Raf-ERK signaling to enhance the activity of T-type calcium channel (TTCC). The presence of the voltage-gated calcium channel (VGCC) beta-subunit inhibits the ZnT1-induced augmentation of TTCC function, possibly through the reduction of ZnT1-induced activation of Ras-ERK signaling.
Article
Medicine, Research & Experimental
Bingqian Wang, Xiaopeng Li, Ning Yu, Liang Yang, Chengrui Nan, Lisi Guo, Zongmao Zhao
Summary: This study found that the expression levels of alpha 2 delta 1 and TSP1/2 in brain tissues can be altered by ICH, which in turn affects synapse formation and functional recovery.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2022)
Article
Multidisciplinary Sciences
Serap Erdogmus, Axel R. Concepcion, Megumi Yamashita, Ikjot Sidhu, Anthony Y. Tao, Wenyi Li, Pedro P. Rocha, Bonnie Huang, Ralph Garippa, Boram Lee, Amy Lee, Johannes W. Hell, Richard S. Lewis, Murali Prakriya, Stefan Feske
Summary: The regulatory beta subunit of voltage-gated calcium channels regulates T cell function despite no evidence that these channels were functional within T cells during activation.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Enling Zhan, Jie Jiang, Ying Wang, Kexin Zhang, Tao Tang, Yiqu Chen, Zhongqiang Jia, Qiuxia Wang, Chunqing Zhao
Summary: This study identified a homolog Shisa gene in the two-spotted spider mite and functionally examined its role as the auxiliary subunit of GABARs. Electrophysiological assays confirmed the formation of a functional GABA-activated channel in Xenopus laevis oocytes. These findings contribute to the understanding of invertebrate Shisa and its involvement in inhibitory transmission.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2023)
Article
Multidisciplinary Sciences
Maria Casas, Karl D. Murray, Keiko Hino, Nicholas C. Vierra, Sergi Simo, James S. Trimmer, Rose E. Dixon, Eamonn J. Dickson
Summary: The loss of NPC1 function alters the nanoscale distribution and function of ion channels, leading to abnormal calcium entry, mitochondrial dysfunction, and neurotoxicity. These findings provide insights into the molecular mechanisms connecting NPC1 loss to NPC-associated neuropathology.
NATURE COMMUNICATIONS
(2023)
Article
Anesthesiology
Manuela Nieto-Rostro, Ryan Patel, Anthony H. H. Dickenson, Annette C. C. Dolphin
Summary: In this study, the expression pattern of Ca(V)2.2, a voltage-gated calcium channel, in primary afferent terminals in the dorsal horn was visualized using a knockin mouse model. The increase in Ca(V)2.2 expression following partial sciatic nerve ligation (PSNL) was observed in large and medium dorsal root ganglion (DRG) neurons as well as their synaptic terminals. The upregulation of Ca(V)2.2 expression was dependent on the auxiliary subunit a(2)d-1 and was associated with enhanced synaptic transmission.
Article
Multidisciplinary Sciences
Yue Li, Tian Yuan, Bo Huang, Feng Zhou, Chao Peng, Xiaojing Li, Yunlong Qiu, Bei Yang, Yan Zhao, Zhuo Huang, Daohua Jiang
Summary: In this study, the cryo-EM structures of human Na(V)1.6/beta 1/beta 2 alone and complexed with 4,9-ah-TTX were determined, providing insights into the molecular mechanism of Na(V)1.6 inhibition and ion conductance.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Hyun Jong Kim, Seorin Park, Hui Young Shin, Yu Ran Nam, Phan Thi Lam Hong, Young-Won Chin, Joo Hyun Nam, Woo Kyung Kim
Summary: This study found that alpha-mangostin suppresses T cell stimulation by inhibiting ORAI1, K(v)1.3, and K(Ca)3.1 ion channels, thereby inhibiting immune cell activity. Additionally, alpha-mangostin demonstrates its anti-inflammatory effect by regulating calcium signals.
Review
Biochemistry & Molecular Biology
Yuting Chen, Qingqing Wu, Zhengsheng Jin, Yanlan Qin, Fancui Meng, Guilong Zhao
Summary: This study reviewed the latest progress in the discovery and development of gabapentinoids for the treatment of chronic neuropathic pain (NP). The structure-activity relationship (SAR) of gabapentinoids was analyzed through pharmacophore modeling. The findings provide valuable insights for the future design of novel therapeutic agents targeting the voltage-gated calcium channel (VGCC) alpha 2 delta subunit.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Organic
He Jinyan, Tian Fuyun, Wu Qingqing, Zheng Yueming, Chen Yuting, Xu Haiyan, Jin Zhengsheng, Zhan Li, Cheng Xinqiang, Gu Yueling, Gao Zhaobing, Zhao Guilong
Summary: Voltage-gated calcium channel (VGCC) alpha 2 delta subunit ligands are highly effective and safe drugs for chronic neuropathic pain. In this study, bulky alkyl moieties with constrained conformation were designed and synthesized to investigate their effect on the bioactivity of VGCC alpha 2 delta subunit ligands. The results showed that [3.3.3]propellane is tolerated but bulkier than optimal size, and modification or replacement of the amino group in GABA chain significantly decreases or eliminates the bioactivity. The structure-activity relationship revealed in this study may aid in the design of novel VGCC alpha 2 delta subunit ligands.
CHINESE JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Ngeywo Tolbert Kaner, Yadong Wei, Tao Ying, Xiaodong Xu, Weiqi Li, Ali Raza, Xingji Li, Jianqun Yang, YongYuan Jiang, Wei Quan Tian
Summary: This study predicts the giant and anisotropic shift current (SC) in 2D monolayer alpha-AsP and alpha-NP based on first-principle calculations, with multiple peaks across a wide range of frequencies. The dominant SC components are in-plane and reach peak values of -154 mu AV(-2) and 87 mu AV(-2) in the UV region for alpha-AsP and alpha-NP, respectively. The findings recommend new photovoltaic materials with strong SC peaks spread across the electromagnetic spectrum, particularly in the UV region.
ADVANCED THEORY AND SIMULATIONS
(2022)
Article
Multidisciplinary Sciences
Zhou Chen, Abhisek Mondal, Fayal Abderemane-Ali, Seil Jang, Sangeeta Niranjan, Jose L. Montano, Balyn W. W. Zaro, Daniel L. L. Minor Jr
Summary: This article reveals the assembly mechanism of high-voltage-activated calcium channels and their interactions with chaperone proteins through cryo-electron microscopy structure. The results indicate that chaperone proteins play an important role in the process of channel assembly.
Article
Chemistry, Organic
Saurabh K. Tiwari, Km Neha Shivhare, Manoj K. Patel, Vikas Yadav, Mohd Nazeef, I. R. Siddiqui
Summary: We report an eco-friendly and facile strategy for the synthesis of 1,4-dihydropyridine (1,4-DHP) derivatives through a one pot multi-component Hantzsch reaction using glycerol as a promoting medium. The protocol offers a greener, economical, and expeditious synthesis of biologically significant 1,4-DHPs with moderate to excellent yields under metal-free mild reaction conditions. The additional advantages include operational simplicity, cost effectiveness, and reusability with the avoidance of hazardous volatile solvents.
POLYCYCLIC AROMATIC COMPOUNDS
(2022)
Review
Pharmacology & Pharmacy
Cristiana-Ioana Bercea, Graeme S. Cottrell, Francesco Tamagnini, Alister J. McNeish
Summary: Hypertension is characterised by impaired vasodilation, which can be improved by omega-3 polyunsaturated fatty acids such as DHA and EPA. These fatty acids also have vasodilatory effects on vascular smooth muscle cells (VSMCs) by opening potassium channels and possibly voltage-activated potassium channels, leading to hyperpolarisation and relaxation. Structural manipulation of omega-3 PUFAs may lead to novel therapeutic strategies.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Cell Biology
Vasco C. Silveirinha, Hong Lin, Shota Tanifuji, Sumiko Mochida, Graeme S. Cottrell, Helena Cimarosti, Gary J. Stephens
Summary: SUMOylation is an important post-translational modification process that involves the covalent attachment of SUMO protein to target proteins. The study found that SUMO-1 protein can modulate the function of the Cav2.2 voltage-gated calcium channel, affecting neurotransmitter release and providing novel targets for SUMOylation pathways.
Review
Biochemistry & Molecular Biology
Dirk Roosterman, Graeme Stuart Cottrell
Summary: The Citric Acid Cycle, initially proposed in 1937 by Sir H. A Krebs, is a unidirectional cycle crucial for the degradation of lactic acid and energy production. The heart lactate dehydrogenase center · proton-linked monocarboxylate transporter 1 complex plays a key role in catalyzing the initial step of the cycle by oxidizing lactate to pyruvate. By incorporating oxaloacetic acid into the cycle, anabolic processes can be integrated, allowing organisms to recover ATP more efficiently.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Dirk Roosterman, Graeme Stuart Cottrell
Summary: Schizophrenia is a chronic and severe mental disorder affecting over 20 million people worldwide. Research suggests disturbances in glucose metabolism may be a potential mechanism for the disease, and a 'two-cell' model of glucose metabolism has been developed to explain treatment effects. The model challenges established concepts and suggests schizophrenia can be formulated in two steps involving dysregulation of glucose signaling pathways.
MOLECULAR PSYCHIATRY
(2021)
Review
Clinical Neurology
Eric R. Wengert, Manoj K. Patel
Summary: Voltage-gated sodium channels play a crucial role in generating action potentials in the nervous system, with a persistent sodium current contributing to normal neuronal function but potentially playing a pathogenic role in epilepsy. Targeting the persistent sodium current may hold promise for developing novel anti-seizure medication strategies.
Review
Cell & Tissue Engineering
Mesude Bicer, Graeme S. Cottrell, Darius Widera
Summary: As populations age, osteoporosis and osteoporosis-related fractures are becoming increasingly prevalent degenerative bone diseases. Three-dimensional cell culture technology may serve as an alternative therapeutic approach to tackle osteoporosis, allowing for more physiological expansion and differentiation of stem cells.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Clinical Neurology
Ian C. Wenker, Frida A. Teran, Eric R. Wengert, Pravin K. Wagley, Payal S. Panchal, Elizabeth A. Blizzard, Priyanka Saraf, Jacy L. Wagnon, Howard P. Goodkin, Miriam H. Meisler, George B. Richerson, Manoj K. Patel
Summary: The study revealed that apnea coincident with the tonic phase of a seizure, and subsequent failure to resume breathing, are determining events that cause seizure-induced death in Scn8a mutant mice.
ANNALS OF NEUROLOGY
(2021)
Article
Neurosciences
Eric R. Wengert, Ian C. Wenker, Elizabeth L. Wagner, Pravin K. Wagley, Ronald P. Gaykema, Jung-Bum Shin, Manoj K. Patel
Summary: This study demonstrates that mice harboring an Scn8a allele with a patient-derived mutation are susceptible to audiogenic seizures and seizure-induced death, providing a new model for studying seizure-induced death. Activation of adrenergic receptors is necessary and sufficient for recovery of breathing and prevention of seizure-induced death in this novel audiogenic seizure-induced death model.
FRONTIERS IN NEUROSCIENCE
(2021)
Editorial Material
Clinical Neurology
Eric R. Wengert, Manoj K. Patel
Article
Biochemistry & Molecular Biology
Enrico C. Torre, Mesude Bicer, Graeme S. Cottrell, Darius Widera, Francesco Tamagnini
Summary: Adipose-derived mesenchymal stromal cells (ASCs) have the potential to differentiate into various cell types and exhibit spontaneous Ca2+ oscillations. The effects of differentiation treatments on ASCs' Ca2+ dynamics, in terms of oscillation fraction and frequency, were examined in this study. Both adipogenic and osteogenic differentiation resulted in reduced Ca2+ dynamics, with adipogenic differentiation showing a more pronounced effect. Changes in Ca2+ oscillations were observed as early as 7 days in vitro (DIV). Further research is needed to understand the molecular and mechanistic correlates of these changes for the development of interventions in regenerative medicine.
Article
Pharmacology & Pharmacy
Ankita Sharma, Shardulya Shukla, Abul Quasim, Manoj Kumar Patel, Raj Kumar, Om Prakash Chaurasia, Shweta Saxena
Summary: This study developed an in vitro regeneration protocol for Rubia cordifolia using nodal and leaf explants, and compared the phytochemical profiles of in vitro grown leaves (RUML) and roots (RUMR). The results showed that both leaves and roots contain medicinal compounds, with 8 compounds commonly present in both extracts.
ANNALS OF PHYTOMEDICINE-AN INTERNATIONAL JOURNAL
(2021)
Article
Engineering, Electrical & Electronic
Aarti Chauhan, Manoj Kumar Patel, Shilpa Chaudhary, Manoj Kumar Nayak, Surender Singh Saini, Pratap Pullammanappallil, Nadarajah Manivannan, Geoffrey Robert Mitchell, Wamadeva Balachandran
Summary: This research aims to evaluate the chargeability of sodium hypochlorite and an air-assisted electrostatic disinfection device. Five different surfaces were examined to assess efficacy, survival time, off-target losses, spray coverage, and disinfectant consumption. The results showed that sodium hypochlorite achieved a significant charge-to-mass ratio of 2.43 mC/kg at specific conditions and effectively eliminated Pseudomonas aeruginosa, Clostridium perfringens, and Bacteriophage MS2 colonies at a concentration of 1000 mg/L.
JOURNAL OF ELECTROSTATICS
(2023)
Article
Multidisciplinary Sciences
Aarti Chauhan, Manoj Kumar Patel, Manoj Kumar Nayak, Surender Singh Saini
Summary: Electrostatic spraying is an effective method for disinfecting surfaces to prevent transmission of SARS-CoV-2. The design and performance of a motorized pressure-nozzle based handheld electrostatic disinfection device were optimized, and the chargeability of various disinfectants was investigated.
Review
Biophysics
Auste Kanapeckaite, Neringa Burokien, Asta Mazeikiene, Graeme S. Cottrell, Darius Widera
Summary: Epigenetic research is shifting towards multidisciplinary strategies that incorporate biophysical analysis tools, in order to advance understanding of biomarkers and regulatory processes in health and disease. By integrating biophysics with bioinformatics, machine learning, and artificial intelligence, new insights into complex epigenetic processes can be gained, with potential applications in translational and clinical research. This transformation allows for the development of high-throughput applications and the utilization of advanced methods in clinical practice and diagnostics.
BIOPHYSICAL REPORTS
(2021)