1. Turner, M. D., Nedjai, B., Hurst, T. & Pennington, D. J. Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease. Biochim. Biophys. Acta. 1843, 2563–2582 (2014).
2. Mittal, M., Siddiqui, M. R., Tran, K., Reddy, S. P. & Malik, A. B. Reactive oxygen species in inflammation and tissue injury. Antioxid
Redox Signal 20, 1126–1127 (2014).
3. Sharif, O., Bolshakov, V. N., Raines, S., Newham, P. & Perkins, N. D. Transcriptional profiling of the LPS induced NF-kappaB
response in macrophages. BMC Immunol. 8, 1. https://doi.org/10.1186/1471-2172-8-1 (2007).
4. Liu, T., Chang, L., Joo, D. & Sung, S. C. NF-κB signaling in inflammation. Signal Transduct. Targ. Ther. 2, 17023. https://doi.org/
10.1038/sigtrans.2017.23 (2017).
5. Kany, S., Vollrath, J. T. & Relja, B. Cytokines in inflammatory disease. Int. J. Mol. Sci. 20, 6008. https://doi.org/10.3390/ijms202360
08 (2019).
6. Diskin, C. & Palsson-McDermott, E. M. Metabolic modulation in macrophage effector function. Front. Immunol. 9, 270. https://
doi.org/10.3389/fimmu.2018.00270 (2018).
7. Kruger, A. et al. The pentose phosphate pathway is a metabolic redox sensor and regulates transcription during the antioxidant
response. Antioxid. Redox. Signal. 15, 311–324 (2011).
8. Yu, X. H., Zhang, D. W., Cheng, X. L. & Tang, C. K. Itaconate: an emerging determinant of inflammation in activated macrophages.
Immunol. Cell Biol. 97, 134–141 (2019).
9. Zhu, X. et al. Itaconic acid exerts anti-inflammatory and antibacterial effects via promoting pentose phosphate pathway to produce
ROS. Sci. Rep. 11, 18173. https://doi.org/10.1038/s41598-021-97352-x (2021).
10. Tannahill, G. M. et al. Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature 163, 238–242 (2013).
11. Khouri, C. et al. Hierarchical evaluation of electrical stimulation protocols for chronic wound healing: An effect size meta-analysis.
Wound. Rep. Reg. 25, 883–891 (2017).
12. Lala, D., Spaulding, S. J., Burke, S. M. & Houghton, P. E. Electrical stimulation therapy for the treatment of pressure ulcers in
individuals with spinal cord injury: A systematic review and meta-analysis. Int. Wound. J. 13, 1214–1226 (2016).
13. Polak, A. et al. A prospective, randomized, controlled, clinical study to evaluate the efficacy of high-frequency ultrasound in the
treatment of Stage II and Stage III pressure ulcers in geriatric patients. Ostomy. Wound Manag. 60, 16–28 (2014).
14. Yamaguchi, A. et al. Pulsed-ultrasound irradiation induces the production of itaconate and attenuates inflammatory responses in
macrophages. J. Inflamm. Res. 15, 2387–2395 (2022).
15. Srirussamee, K., Mobini, S., Cassidy, N. J. & Cartmell, S. H. Direct electrical stimulation enhances osteogenesis by inducing Bmp2
and Spp1 expressions from macrophages and preosteoblasts. Biotechnol. Bioeng. 116, 3421–3432 (2019).
16. Kao, C. H. et al. High-frequency electrical stimulation can be a complementary therapy to promote nerve regeneration in diabetic
rats. PLoS One 8, e79078. https://doi.org/10.1371/journal.pone.0079078 (2013).
17. Meneses, G. et al. Electric stimulation of the vagus nerve reduced mouse neuroinflammation induced by lipopolysaccharide. J
Inflamm 13, 33. https://doi.org/10.1186/s12950-016-0140-5 (2016).
18. Viola, A., Munari, F., Sánchez-Rodríguez, R., Scolaro, T. & Castegna, A. The metabolic signature of macrophage responses. Front.
Immunol. 10, 1462. https://doi.org/10.3389/fimmu.2019.01462 (2019).
19. Ma, R. et al. Pck1-directed glycogen metabolic program regulates formation and maintenance of memory CD8 + T cells. Nat. Cell
Biol. 20, 21–27 (2018).
20. Jiang, P., Du, W. & Wu, M. Regulation of the pentose phosphate pathway in cancer. Protein Cell 5, 592–602 (2014).
21. Mailloux, R. J. et al. The tricarboxylic acid cycle, an ancient metabolic network with a novel twist. PLoS One 2, e690. https://doi.
org/10.1371/journal.pone.0000690 (2007).
22. He, L. et al. Prevention of oxidative stress by α-ketoglutarate via activation of CAR signaling and modulation of the expression of
key antioxidant-associated targets in vivo and in vitro. J Agric Food Chem. 66, 11273–11283 (2018).
23. Cutalo, M., Campitiello, R., Gotelli, E. & Soldano, S. The role of M1/M2 macrophage polarization in rheumatoid arthritis synovitis.
Front Immunol. 13, 867260. https://doi.org/10.3389/fimmu.2022.867260 (2022).
24. Biswas, S. K. Does the Interdependence between oxidative stress and inflammation explain the antioxidant paradox?. Oxid. Med.
Cell Longev. 2016, 5698931. https://doi.org/10.1155/2016/5698931 (2016).
25. Kelley, N., Jeltema, D., Duan, Y. & He, Y. The NLRP3 inflammasome: An overview of mechanisms of activation and regulation.
Int. J. Mol. Sci. 20, 3328. https://doi.org/10.3390/ijms20133328 (2019).
26. Beckley, A. J. G., Lan, L. Q., Aono, S., Wang, L. & Shi, J. Caspase-1 activation and mature interleukin-1β release are uncoupled
events in monocytes. World J. Biol. Chem. 4, 30–4. https://doi.org/10.4331/wjbc.v4.i2.30 (2013).
27. Sutterwala, F. S. et al. Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1. Immunity 34(317–327), 7 (2006).
28. Cong, L. et al. Electrical stimulation inhibits Val-boroPro-induced pyroptosis in THP-1 macrophages via sirtuin3 activation to
promote autophagy and inhibit ROS generation. Aging 12, 6415–6435 (2020).
29. Uemura, M. et al. Monophasic pulsed 200-μA current promotes galvanotaxis with polarization of actin filament and integrin α2β1
in human dermal fibroblasts. Eplasty 16, e6 (2016).
30. Yoshikawa, Y. et al. Monophasic pulsed microcurrent of 1–8 Hz Increases the number of human dermal fibroblasts. Prog. Rehabil.
Med. 1, 20160005. https://doi.org/10.2490/prm.20160005 (2016).
Scientific Reports |
(2023) 13:17819 |
https://doi.org/10.1038/s41598-023-44886-x
Vol.:(0123456789)
www.nature.com/scientificreports/
31. Yoshikawa, Y. et al. Efficacy of low-frequency monophasic pulsed microcurrent stimulation therapy in undermining pressure
injury: A double-blind crossover-controlled study. Prog. Rehabil. Med. 7, 20220045. https://d
oi.o
rg/1 0.2 490/p
rm.2 02200 45 (2022).
32. Shihan, M. H., Novo, S. G., Le Marchand, S. J., Wang, Y. & Duncan, M. K. A simple method for quantitating confocal fluorescent
images. Biochem. Biophys. Rep. 25, 100916. https://doi.org/10.1016/j.bbrep.2021.100916 (2021).
33. Kato, H., Izumi, Y., Hasunuma, T., Matsuda, F. & Kondo, A. Widely targeted metabolic profiling analysis of yeast central metabolites.
J. Biosci. Bioeng. 113, 665–673 (2012).
34. Kanda, Y. Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant. 48,
452–458 (2013).
Acknowledgements
This study was supported by JSPS KAKENHI [Grant Numbers: 20K19398 and 21H03852].
Author contributions
M.U., N.M., and T.I. designed experiments. M.U., A.Y., X.M., M.M., Y.N., and T.H. performed experiments and
analyzed data. M.U., N.M., T.I., J.Y., J.W., H.K., and H.F. drafted and revised manuscript. All authors have read
and approved the final version of the manuscript before publication.
Competing interests The authors declare no competing interests.
Additional information
Supplementary Information The online version contains supplementary material available at https://doi.org/
10.1038/s41598-023-44886-x.
Correspondence and requests for materials should be addressed to N.M.
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