{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T10:50:42Z","timestamp":1770288642813,"version":"3.49.0"},"reference-count":59,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T00:00:00Z","timestamp":1586390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012544","name":"China Medical University, Taiwan","doi-asserted-by":"publisher","award":["CMU106-BC-2"],"award-info":[{"award-number":["CMU106-BC-2"]}],"id":[{"id":"10.13039\/501100012544","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 106-2320-B-039-019"],"award-info":[{"award-number":["MOST 106-2320-B-039-019"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Irreversible pulpitis is an extremely painful condition and its consequence in the central nervous system (CNS) remains unclear. A mouse model of dental pulp injury (DPI) resembles the irreversible pulpitis profile in humans. This study sought to determine whether pain induced by DPI activates microglia and astrocytes in the trigeminal subnucleus caudalis (Vc), as well as increases levels of proinflammatory cytokines, and whether electroacupuncture (EA) can be a potential analgesic and neuroprotective therapy following DPI. Pain behavior was measured via head-withdrawal threshold (HWT) and burrowing behavior at days 1, 3, 7, 14 and 21 after DPI. A marked decrease in HWT and burrowing activity was observed from day 1 to 14 after DPI and no changes were seen on day 21. Microglial and astrocytes activation; along with high cytokine (TNF\u03b1, IL-1\u03b2, and IL-6) levels, were observed in the Vc at 21 days after DPI. These effects were attenuated by verum (local and distal) EA, as well as oral ibuprofen administration. The results suggest that DPI-induced pain and glial activations in the Vc and EA exert analgesic efficacy at both local and distal acupoints. Furthermore, verum (local and distal) EA might be associated with the modulations of microglial and astrocytes activation.<\/jats:p>","DOI":"10.3390\/ijms21072628","type":"journal-article","created":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T14:42:03Z","timestamp":1586443323000},"page":"2628","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Analgesic and Neuroprotective Effects of Electroacupuncture in a Dental Pulp Injury Model\u2014A Basic Research"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9486-5985","authenticated-orcid":false,"given":"Sharmely Sharon","family":"Ballon Romero","sequence":"first","affiliation":[{"name":"Graduate Institute of Acupuncture Science, China Medical University, Taichung 40402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9510-3146","authenticated-orcid":false,"given":"Yu-Chen","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate Institute of Acupuncture Science, China Medical University, Taichung 40402, Taiwan"},{"name":"Department of Acupuncture, China Medical University Hospital, Taichung 40447, Taiwan"},{"name":"Chinese Medicine Research Center, China Medical University, Taichung 40402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3008-8165","authenticated-orcid":false,"given":"Lih-Jyh","family":"Fuh","sequence":"additional","affiliation":[{"name":"School of Dentistry, College of Dentistry, China Medical University; Taichung 40402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsin-Yi","family":"Chung","sequence":"additional","affiliation":[{"name":"Graduate Institute of Acupuncture Science, China Medical University, Taichung 40402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0749-1562","authenticated-orcid":false,"given":"Shih-Ya","family":"Hung","sequence":"additional","affiliation":[{"name":"Graduate Institute of Acupuncture Science, China Medical University, Taichung 40402, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, Taichung 40447, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8946-7939","authenticated-orcid":false,"given":"Yi-Hung","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Acupuncture Science, China Medical University, Taichung 40402, Taiwan"},{"name":"Chinese Medicine Research Center, China Medical University, Taichung 40402, Taiwan"},{"name":"Department of Photonics and Communication Engineering, Asia University, Taichung 41354, Taiwan"},{"name":"Brain Disease Research Center, China Medical University Hospital, Taichung 40447, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1111\/jcmm.12988","article-title":"Pannexin3 inhibits TNF-\u03b1-induced inflammatory response by suppressing NF-\u03baB signalling pathway in human dental pulp cells","volume":"21","author":"Song","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S94","DOI":"10.1111\/jcpe.12677","article-title":"Global epidemiology of dental caries and severe periodontitis\u2013a comprehensive review","volume":"44","author":"Frencken","year":"2017","journal-title":"J. Clin. Periodontol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.joen.2018.11.017","article-title":"Microbiome of Deep Dentinal Caries from Reversible Pulpitis to Irreversible Pulpitis","volume":"45","author":"Zheng","year":"2019","journal-title":"J. Endod."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.joen.2005.10.029","article-title":"A Cochrane systematic review finds no evidence to support the use of antibiotics for pain relief in irreversible pulpitis","volume":"32","author":"Keenan","year":"2006","journal-title":"J. Endod."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Khan, A., and Hargreaves, K.M. (2010). Animal models of orofacial pain. Analgesia, Humana Press.","DOI":"10.1007\/978-1-60327-323-7_8"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1177\/10454411990100010101","article-title":"Dental injury models: Experimental tools for understanding neuroinflammatory interactions and polymodal nociceptor functions","volume":"10","author":"Byers","year":"1999","journal-title":"Crit. Rev. Oral Biol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"198","DOI":"10.3389\/fimmu.2017.00198","article-title":"Cellular and molecular characterization of microglia: A unique immune cell population","volume":"8","author":"Sousa","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/glia.10161","article-title":"Microglia as a source and target of cytokines","volume":"40","author":"Hanisch","year":"2002","journal-title":"Glia"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/S0165-5728(99)00218-0","article-title":"Astrocytes modulate macrophage phagocytosis of myelin in vitro","volume":"102","author":"Smith","year":"2000","journal-title":"J. Neuroimmunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s00401-009-0622-0","article-title":"Microglia: Biology and pathology","volume":"119","author":"Graeber","year":"2010","journal-title":"Acta Neuropathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.archoralbio.2010.06.007","article-title":"Involvement of microglial activation in the brainstem in experimental dental injury and inflammation","volume":"55","author":"Fan","year":"2010","journal-title":"Arch. Oral Biol."},{"key":"ref_12","first-page":"3","article-title":"Pain management for dentists: The role of ibuprofen","volume":"2","author":"Pozzi","year":"2011","journal-title":"Ann. Stomatol."},{"key":"ref_13","first-page":"10","article-title":"Use of nonsteroidal antiinflammatory drugs in dental practice: A review","volume":"12","year":"2007","journal-title":"Med. OralPatol. Oral Y Cirug\u00eda Bucal"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wu, H.M., Tang, J.L., Lin, X.P., Lau, J.T., Leung, P.C., Woo, J., and Li, Y. (2006). Acupuncture for stroke rehabilitation. Cochrane Database Syst. Rev.","DOI":"10.1002\/14651858.CD004131.pub2"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.jams.2017.09.002","article-title":"Comparison of acupuncture with ibuprofen for pain management in patients with symptomatic irreversible pulpitis: A randomized double-blind clinical trial","volume":"10","author":"Murugesan","year":"2017","journal-title":"J. Acupunct. Meridian Stud."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1177\/201010581202100108","article-title":"Acupuncture in dentistry: Its possible role and application","volume":"21","author":"Wong","year":"2012","journal-title":"Proc. Singap. Healthc."},{"key":"ref_17","first-page":"40","article-title":"Temporal dynamics of anxiety phenotypes in a dental pulp injury model","volume":"11","author":"Shang","year":"2015","journal-title":"Mol. Pain"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1038\/nn.2562","article-title":"Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture","volume":"13","author":"Goldman","year":"2010","journal-title":"Nat. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"De Matos, N.M., Pach, D., Xing, J.J., Barth, J., Beyer, L.E., Shi, X., Kern, A., Lukic, N., Ettlin, D.A., and Br\u00fcgger, M. (2019). Evaluating the Effects of Acupuncture Using a Dental Pain Model in Healthy Subjects\u2013A Randomized, Cross-Over Trial. J. Pain.","DOI":"10.1016\/j.jpain.2019.08.013"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0304-3959(99)00009-3","article-title":"Involvement of trigeminal subnucleus caudalis (medullary dorsal horn) in craniofacial nociceptive reflex activity","volume":"81","author":"Tsai","year":"1999","journal-title":"Pain"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"173","DOI":"10.2334\/josnusd.16-0858","article-title":"Neuron-glia interaction is a key mechanism underlying persistent orofacial pain","volume":"59","author":"Iwata","year":"2017","journal-title":"J. Oral Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"227","DOI":"10.2147\/JIR.S141198","article-title":"Electroacupuncture therapy in inflammation regulation: Current perspectives","volume":"11","author":"Park","year":"2018","journal-title":"J. Inflamm. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1016\/j.pain.2013.04.018","article-title":"Paradoxical surrogate markers of dental injury-induced pain in the mouse","volume":"154","author":"Gibbs","year":"2013","journal-title":"Pain\u00ae"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Rossi, H.L., See, L.P., Foster, W., Pitake, S., Gibbs, J., Schmidt, B., Mitchell, C.H., and Abdus-Saboor, I. (2019). Evoked and spontaneous pain assessment during tooth pulp injury. bioRxiv, 742049.","DOI":"10.1101\/742049"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.physbeh.2018.04.020","article-title":"Orofacial neuropathic pain reduces spontaneous burrowing behavior in rats","volume":"191","author":"Deseure","year":"2018","journal-title":"Physiol. Behav."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Matsubara, T., Arai, Y.-C.P., Shiro, Y., Shimo, K., Nishihara, M., Sato, J., and Ushida, T. (2011). Comparative effects of acupressure at local and distal acupuncture points on pain conditions and autonomic function in females with chronic neck pain. Evid.-Based Complementary Altern. Med., 2011.","DOI":"10.1155\/2011\/543291"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1749-8546-7-4","article-title":"Point specificity in acupuncture","volume":"7","author":"Choi","year":"2012","journal-title":"Chin. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lee, S.-H., Kim, C.-E., Lee, I.-S., Jung, W.-M., Kim, H.-G., Jang, H., Kim, S.-J., Lee, H., Park, H.-J., and Chae, Y. (2013). Network analysis of acupuncture points used in the treatment of low back pain. Evid.-Based Complementary Altern. Med., 2013.","DOI":"10.1155\/2013\/402180"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.pain.2005.12.023","article-title":"Activation of glia and microglial p38 MAPK in medullary dorsal horn contributes to tactile hypersensitivity following trigeminal sensory nerve injury","volume":"121","author":"Piao","year":"2006","journal-title":"Pain"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s10735-018-9765-4","article-title":"Activation of satellite glial cells in trigeminal ganglion following dental injury and inflammation","volume":"49","author":"Liu","year":"2018","journal-title":"J. Mol. Histol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Taves, S., Berta, T., Chen, G., and Ji, R.-R. (2013). Microglia and spinal cord synaptic plasticity in persistent pain. Neural Plast., 2013.","DOI":"10.1155\/2013\/753656"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.brainresrev.2008.12.020","article-title":"Role of interleukin-1\u03b2 during pain and inflammation","volume":"60","author":"Ren","year":"2009","journal-title":"Brain Res. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1007\/s12035-018-1076-y","article-title":"TNF\u03b1 in the Trigeminal Nociceptive System Is Critical for Temporomandibular Joint Pain","volume":"56","author":"Bai","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8489","DOI":"10.1523\/JNEUROSCI.2552-08.2008","article-title":"Differential implication of proinflammatory cytokine interleukin-6 in the development of cephalic versus extracephalic neuropathic pain in rats","volume":"28","author":"Mauborgne","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1034\/j.1600-0757.2001.22250103.x","article-title":"Relationship between periodontal disease and systemic health","volume":"25","author":"Garcia","year":"2001","journal-title":"Periodontology 2000"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"241","DOI":"10.4103\/1947-2714.159325","article-title":"Association between periodontitis and Alzheimer\u2019s disease","volume":"7","author":"Abbayya","year":"2015","journal-title":"North Am. J. Med. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1177\/0022034516653604","article-title":"Microglial signaling in chronic pain with a special focus on caspase 6, p38 MAP kinase, and sex dependence","volume":"95","author":"Berta","year":"2016","journal-title":"J. Dent. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.nbd.2010.04.003","article-title":"Acupuncture-mediated inhibition of inflammation facilitates significant functional recovery after spinal cord injury","volume":"39","author":"Choi","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/B978-0-12-407178-0.00006-5","article-title":"Inflammatory pathways in spinal cord injury","volume":"106","author":"David","year":"2012","journal-title":"International Review of Neurobiology"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Lin, D., De La Pena, I., Lin, L., Zhou, S.-F., Borlongan, C., and Cao, C. (2014). The neuroprotective role of acupuncture and activation of the BDNF signaling pathway. Int. J. Mol. Sci., 15.","DOI":"10.3390\/ijms15023234"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1136\/acupmed-2013-010410","article-title":"Acupuncture with non-steroidal anti-inflammatory drugs (NSAIDs) versus acupuncture or NSAIDs alone for the treatment of chronic neck pain: An assessor-blinded randomised controlled pilot study","volume":"32","author":"Cho","year":"2014","journal-title":"Acupunct. Med."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Corder, G., Castro, D.C., Bruchas, M.R., and Scherrer, G. (2018). Endogenous and exogenous opioids in pain. Annu. Rev. Neurosci.","DOI":"10.1146\/annurev-neuro-080317-061522"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.expneurol.2013.11.008","article-title":"Chronic ibuprofen administration reduces neuropathic pain but does not exert neuroprotection after spinal cord injury in adult rats","volume":"252","author":"Navarro","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1089\/neu.2007.0464","article-title":"Ibuprofen enhances recovery from spinal cord injury by limiting tissue loss and stimulating axonal growth","volume":"26","author":"Wang","year":"2009","journal-title":"J. Neurotrauma"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4154","DOI":"10.1523\/JNEUROSCI.4353-06.2007","article-title":"Nonsteroidal anti-inflammatory drugs promote axon regeneration via RhoA inhibition","volume":"27","author":"Fu","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.pneurobio.2008.05.004","article-title":"Neural mechanism underlying acupuncture analgesia","volume":"85","author":"Zhao","year":"2008","journal-title":"Prog. Neurobiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0166-2236(02)00006-1","article-title":"Acupuncture: Neuropeptide release produced by electrical stimulation of different frequencies","volume":"26","author":"Han","year":"2003","journal-title":"Trends Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"E10720","DOI":"10.1073\/pnas.1807991115","article-title":"Median nerve stimulation induces analgesia via orexin-initiated endocannabinoid disinhibition in the periaqueductal gray","volume":"115","author":"Chen","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","first-page":"482","article-title":"Mechanisms of acupuncture\u2013electroacupuncture on persistent pain","volume":"120","author":"Zhang","year":"2014","journal-title":"Anesthesiol. J. Am. Soc. Anesthesiol."},{"key":"ref_50","first-page":"1","article-title":"Inhibiting the LPS-induced enhancement of mEPSC frequency in superficial dorsal horn neurons may serve as an electrophysiological model for alleviating pain","volume":"9","author":"Yang","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.expneurol.2011.11.012","article-title":"ATP receptors gate microglia signaling in neuropathic pain","volume":"234","author":"Trang","year":"2012","journal-title":"Exp. Neurol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.rvsc.2007.04.004","article-title":"A proposed transpositional acupoint system in a mouse and rat model","volume":"84","author":"Yin","year":"2008","journal-title":"Res. Vet. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Gaertner, D.J. (2008). Anesthesia and analgesia for laboratory rodents. Anesth. Analg. Lab. Anim., 240\u2013297.","DOI":"10.1016\/B978-012373898-1.00010-4"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"12549","DOI":"10.1038\/srep12549","article-title":"Toll-like receptor 4 signaling in neurons of trigeminal ganglion contributes to nociception induced by acute pulpitis in rats","volume":"5","author":"Lin","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Huang, F., Zhang, M., Chen, Y.-J., Li, Q., and Wu, A.-Z. (2011). Psychological stress induces temporary masticatory muscle mechanical sensitivity in rats. Biomed. Res. Int., 2011.","DOI":"10.1155\/2011\/720603"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jneumeth.2014.02.001","article-title":"Burrowing and nest building behavior as indicators of well-being in mice","volume":"234","author":"Jirkof","year":"2014","journal-title":"J. Neurosci. Methods"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.brainres.2016.07.007","article-title":"Electroacupuncture inhibits pruritogen-induced spinal microglial activation in mice","volume":"1649","author":"Lin","year":"2016","journal-title":"Brain Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.ejphar.2009.06.026","article-title":"Inhibitory effect of lidocaine on pain and itch using formalin-induced nociception and 5\u2032-guanidinonaltrindole-induced scratching models in mice: Behavioral and neuroanatomical evidence","volume":"616","author":"Inan","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.neuropharm.2015.02.003","article-title":"LC3 overexpression reduces A\u03b2 neurotoxicity through increasing \u03b17nAchR expression and autophagic activity in neurons and mice","volume":"93","author":"Hung","year":"2015","journal-title":"Neuropharmacology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/7\/2628\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:17:06Z","timestamp":1760174226000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/7\/2628"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,9]]},"references-count":59,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["ijms21072628"],"URL":"https:\/\/doi.org\/10.3390\/ijms21072628","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,9]]}}}