medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2025-313medsovet-9379Research ArticleПРАКТИКАPRACTICEПрогнозирование вероятности возникновения отсроченных осложнений после введения препаратов на основе PLAPredicting the likelihood of late complications after administration of PLA-based drug productshttps://orcid.org/0000-0001-8657-9559МоржанаеваМ. А.MorzhanaevaM. A.

Моржанаева Мария Андреевна, к.м.н., врач-косметолог

127473, Москва, 2-й Щемиловский переулок, д. 4

Maria A. Morzhanaeva, Cand. Sci. (Med.), Cosmetologist

4, 2nd  Stchemilovsky Lane, Moscow, 127473

maria_morzhanaeva@mail.ruhttps://orcid.org/0000-0002-5885-4872СвечниковаЕ. В.SvechnikovaE. V.

Свечникова Елена Владимировна, д.м.н., заведующая отделением дерматовенерологии и косметологии, Поликлиника №1 Управления делами Президента Российской Федерации; профессор кафедры кожных и венерических болезней, Российский биотехнологический университет (РОСБИОТЕХ)

1119002, Москва, переулок Сивцев Вражек, д. 26/28; 125080, Москва, Волоколамское шоссе, д. 11

Elena V. Svechnikova, Dr. Sci. (Med.), Head of the Department of Dermatovenereology and Cosmetology, Polyclinic No. 1 of the Office of the President of the Russian Federation; rofessor of the Department of Skin and Sexually Transmitted Diseases, Russian Biotechnological University

26/28, Sivtsev Vrazhek Lane, Moscow, 119002; 11, Volokolamskoe Shosse, Moscow, 125080

elene-elene@bk.ruhttps://orcid.org/0000-0002-0896-1450СтаркинаО. B.StarkinaO. V.

Старкина Ольга Васильевна, руководитель лаборатории биотехнологий

603087, Россия, Нижний Новгород, ул. ВерхнеПечерская, д. 7

Olga V. Starkina, Head of the Biotechnology Laboratory

7, Verkhne-Pecherskaya St., Nizhny Novgorod, 603087

starkina@melsytech.ruhttps://orcid.org/0000-0003-0314-7035ГорскаяА. А.GorskayaA. A.

Горская Антонина Александровна, врач-косметолог, руководитель

603022, Россия, Нижний Новгород, ул. Тимирязева, д. 31а

Antonina A. Gorskaya, Cosmetologist, Head

31а, Timiryazev St., Nizhny Novgorod, 603022

aa.gorskaya@gmail.comМелситек КлиниксРоссияMelsitek ClinicsRussian FederationПоликлиника №1 Управления делами Президента Российской Федерации; Российский биотехнологический университет (РОСБИОТЕХ)РоссияPolyclinic No. 1 of the Office of the President of the Russian Federation; Russian Biotechnological UniversityRussian FederationMelsytech GeneticsРоссияMelsytech GeneticsRussian FederationКлиника “O’LIVE”РоссияO’LIFE ClinicRussian Federation2025100920251913304312Copyright © Моржанаева М.А., Свечникова Е.В., Старкина О.B., Горская А.А., 20252025Моржанаева М.А., Свечникова Е.В., Старкина О.B., Горская А.А.Morzhanaeva M.A., Svechnikova E.V., Starkina O.V., Gorskaya A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/9379Введение

Введение. Филлеры на основе поли-L-молочной кислоты (PLA) корректируют потерю объема кожи, стимулируя фибробласты к синтезу коллагена. Ткани вокруг места инъекции PLA накапливают макрофаги CD68+ и фибробласты CD90+. Они также повышают уровни TGF-β1 и тканевого ингибитора металлопротеиназы 1 (TIMP1), которые способствуют отложению коллагена I и III. Одним из серьезных осложнений после введения филлеров на основе поли-L-молочной кислоты (PLA) является гранулематозное воспаление. Генетическое тестирование представляет большой интерес с точки зрения прогнозирования как эффективности косметологических процедур, так и их безопасности.

Цель

Цель. Определить генетическую предрасположенность к нежелательному фиброзу и вероятность развития гранулематозного воспаления (реакции на инородное тело) после введения препаратов на основе PLA.

Материалы и методы

Материалы и методы. В пилотном исследовании участвовало 54 пациента женского пола, которым были проведены процедуры векторного лифтинга препаратом на основе PLA и проведено генетическое тестирование. Материалом для молекулярно-генетического исследования служил буккальный эпителий. ПЦР проводили с помощью амплификатора Rotor Gene Q (Qiagen, Германия).

Результаты

Результаты. В ходе проведенного исследования были четко определены закономерности развития гранулематозного воспаления у пациентов с полиморфизмом генов IL-4 и IL-13. Сравнение двух групп показало, что маркеры rs2243250_IL-4 и rs20541_IL-13 имеют статистически значимые различия (p < 0,05), что указывает на их потенциальную связь с осложнениями. Корреляционный анализ подтвердил наличие умеренной положительной взаимосвязи между осложнениями в виде отсроченной гранулематозной реакции на введение филлера на основе PLA и вариантом гена rs2243250_IL-4_TT (Rm = 0,480, p = 0,020*), что подчеркивает его значимость в данной выборке.

Выводы

Выводы. Результаты анализа показывают, что наличие полиморфизма и замены в двух аллелях в варианте гена rs2243250_ IL-4_TT значительно увеличивает риск неблагоприятного исхода.

Introduction

Introduction. Poly-L-lactic acid (PLA) fillers correct skin volume loss by stimulating fibroblasts to synthesize collagen. Tissues around the PLA injection site accumulate CD68+ macrophages and CD90+ fibroblasts. They also increase the levels of TGF-β1 and tissue inhibitor of metalloproteinase 1 (TIMP1), which promote the deposition of collagen I and III. One of the serious complications after the introduction of poly-L-lactic acid (PLA) fillers is granulomatous inflammation. Genetic testing is of great interest in terms of predicting both the effectiveness of cosmetic procedures and their safety.

Aim

Aim. To determine the genetic predisposition to unwanted fibrosis and the likelihood of developing granulomatous inflammation (foreign body reaction) after the introduction of PLA-based products.

Materials and methods

Materials and methods. The pilot study involved 54 female patients who underwent vector lifting procedures, a PLA-based drug, and genetic testing. Buccal epithelium served as the material for the molecular genetic study. PCR was performed using a Rotor Gene Q amplifier (Qiagen, Germany).

Results

Results. The study clearly identified patterns of granulomatous inflammation development in patients with IL-4 and IL-13 gene polymorphism. Comparison of the two groups showed that markers rs2243250_IL-4 and rs20541_IL-13 have statistically significant differences (p < 0.05), indicating their potential association with complications. Correlation analysis confirmed the presence of a moderate positive relationship between complications in the form of a delayed granulomatous reaction to the introduction of a PLA-based filler and the rs2243250_IL-4_TT gene (Rm = 0.480, p = 0.020*), which emphasizes its significance in this sample. Univariate analysis showed that the rs2243250_IL-4_TT gene, indicating a high mutation, significantly increases the risk of an unfavorable outcome (OR = 32.008, p = 0.011*).

Conclusions

Conclusions. Findings show that the presence of polymorphism and substitution in two alleles in the rs2243250_IL-4_TT gene variant significantly increases the risk of adverse outcomes.

полимолочная кислотагранулематозное воспалениеCOL1COL3MMP1MMP3IL-6IL-4IL-13TIMP1векторный лифтингPLAинтерлейкиныколлагеностимуляторыфиброзгенетический скринингpolylactic acidgranulomatous inflammationCOL1COL3MMP1MMP3IL-6IL-4IL-13TIMP1vector-liftingPLAinterleukinscollagen stimulatorsfibrosisgenetic screeningReferencesParola M, Pinzani M. Pathophysiology of Organ and Tissue Fibrosis. Mol Aspects Med. 2019;65:1. https://doi.org/10.1016/j.mam.2019.02.001.Parola M, Pinzani M. Pathophysiology of Organ and Tissue Fibrosis. Mol Aspects Med. 2019;65:1. https://doi.org/10.1016/j.mam.2019.02.001.Henderson NC, Rieder F, Wynn TA. Fibrosis: from mechanisms to medicines. Nature. 2020;587(7835):555–566. https://doi.org/10.1038/s41586-0202938-9.Henderson NC, Rieder F, Wynn TA. Fibrosis: from mechanisms to medicines. Nature. 2020;587(7835):555–566. https://doi.org/10.1038/s41586-0202938-9.Zhao X, Kwan JYY, Yip K, Liu PP, Liu FF. Targeting metabolic dysregulation for fibrosis therapy. Nat Rev Drug Discov. 2020;19(1):57–75. https://doi.org/10.1038/s41573-019-0040-5.Zhao X, Kwan JYY, Yip K, Liu PP, Liu FF. Targeting metabolic dysregulation for fibrosis therapy. Nat Rev Drug Discov. 2020;19(1):57–75. https://doi.org/10.1038/s41573-019-0040-5.Perez OA, Berman B. Cytokines and Chemokines. In: Gaspari A, Tyring S (eds.). Clinical and Basic Immunodermatology. Springer London; 2002.Perez OA, Berman B. Cytokines and Chemokines. In: Gaspari A, Tyring S (eds.). Clinical and Basic Immunodermatology. Springer London; 2002.Tanaka T, Narazaki M, Kishimoto T. Interleukin (IL-6) Immunotherapy. Cold Spring Harb Perspect Biol. 2018;10(8):a028456. https://doi.org/10.1101/cshperspect.a028456.Tanaka T, Narazaki M, Kishimoto T. Interleukin (IL-6) Immunotherapy. Cold Spring Harb Perspect Biol. 2018;10(8):a028456. https://doi.org/10.1101/cshperspect.a028456.Johnson BZ, Stevenson AW, Prêle CM, Fear MW, Wood FM. The Role of IL-6 in Skin Fibrosis and Cutaneous Wound Healing. Biomedicines. 2020;8(5):101. https://doi.org/10.3390/biomedicines8050101.Johnson BZ, Stevenson AW, Prêle CM, Fear MW, Wood FM. The Role of IL-6 in Skin Fibrosis and Cutaneous Wound Healing. Biomedicines. 2020;8(5):101. https://doi.org/10.3390/biomedicines8050101.Dalwadi H, Krysan K, Heuze-Vourc’h N, Dohadwala M, Elashoff D, Sharma S et al. Cyclooxygenase-2-dependent activation of signal transducer and activator of transcription 3 by interleukin-6 in non-small cell lung cancer. Clin Cancer Res. 2005;11(21):7674–7682. https://doi.org/10.1158/1078-0432.CCR-05-1205.Dalwadi H, Krysan K, Heuze-Vourc’h N, Dohadwala M, Elashoff D, Sharma S et al. Cyclooxygenase-2-dependent activation of signal transducer and activator of transcription 3 by interleukin-6 in non-small cell lung cancer. Clin Cancer Res. 2005;11(21):7674–7682. https://doi.org/10.1158/1078-0432.CCR-05-1205.Johnson DE, O’Keefe RA, Grandis JR. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol. 2018;15(4):234–248. https://doi.org/10.1038/nrclinonc.2018.8.Johnson DE, O’Keefe RA, Grandis JR. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol. 2018;15(4):234–248. https://doi.org/10.1038/nrclinonc.2018.8.Moodley YP, Misso NL, Scaffidi AK, Fogel-Petrovic M, McAnulty RJ, Laurent GJ et al. Inverse effects of interleukin-6 on apoptosis of fibroblasts from pulmonary fibrosis and normal lungs. Am J Respir Cell Mol Biol. 2003;29(4):490–498. https://doi.org/10.1165/rcmb.2002-0262OC.Moodley YP, Misso NL, Scaffidi AK, Fogel-Petrovic M, McAnulty RJ, Laurent GJ et al. Inverse effects of interleukin-6 on apoptosis of fibroblasts from pulmonary fibrosis and normal lungs. Am J Respir Cell Mol Biol. 2003;29(4):490–498. https://doi.org/10.1165/rcmb.2002-0262OC.Li W, He P, Huang Y, Li YF, Lu J, Li M et al. Selective autophagy of intracellular organelles: recent research advances. Theranostics. 2021;11(1):222–256. https://doi.org/10.7150/thno.49860.Li W, He P, Huang Y, Li YF, Lu J, Li M et al. Selective autophagy of intracellular organelles: recent research advances. Theranostics. 2021;11(1):222–256. https://doi.org/10.7150/thno.49860.Takagaki Y, Lee SM, Dongqing Z, Kitada M, Kanasaki K, Koya D. Endothelial autophagy deficiency induces IL6 – dependent endothelial mesenchymal transition and organ fibrosis. Autophagy. 2020;16(10):1905–1914. https://doi.org/10.1080/15548627.2020.1713641.Takagaki Y, Lee SM, Dongqing Z, Kitada M, Kanasaki K, Koya D. Endothelial autophagy deficiency induces IL6 – dependent endothelial mesenchymal transition and organ fibrosis. Autophagy. 2020;16(10):1905–1914. https://doi.org/10.1080/15548627.2020.1713641.Chen R, Sun Y, Cui X, Ji Z, Kong X, Wu S et al. Autophagy promotes aortic adventitial fibrosis via the IL-6/Jak1 signaling pathway in Takayasu’s arteritis. J Autoimmun. 2019;99:39–47. https://doi.org/10.1016/j.jaut.2019.01.010.Chen R, Sun Y, Cui X, Ji Z, Kong X, Wu S et al. Autophagy promotes aortic adventitial fibrosis via the IL-6/Jak1 signaling pathway in Takayasu’s arteritis. J Autoimmun. 2019;99:39–47. https://doi.org/10.1016/j.jaut.2019.01.010.Noble PW, Barkauskas CE, Jiang D. Pulmonary fibrosis: patterns and perpetrators. J Clin Invest. 2012;122(8):2756–2762. https://doi.org/10.1172/JCI60323.Noble PW, Barkauskas CE, Jiang D. Pulmonary fibrosis: patterns and perpetrators. J Clin Invest. 2012;122(8):2756–2762. https://doi.org/10.1172/JCI60323.Saito F, Tasaka S, Inoue K, Miyamoto K, Nakano Y, Ogawa Y et al. Role of interleukin-6 in bleomycin-induced lung inflammatory changes in mice. Am J Respir Cell Mol Biol. 2008;38(5):566–571. https://doi.org/10.1165/ rcmb.2007-0299OC.Saito F, Tasaka S, Inoue K, Miyamoto K, Nakano Y, Ogawa Y et al. Role of interleukin-6 in bleomycin-induced lung inflammatory changes in mice. Am J Respir Cell Mol Biol. 2008;38(5):566–571. https://doi.org/10.1165/ rcmb.2007-0299OC.Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008;453(7193):314–321. https://doi.org/10.1038/nature07039.Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008;453(7193):314–321. https://doi.org/10.1038/nature07039.Profyris C, Tziotzios C, Do Vale I. Cutaneous scarring: Pathophysiology, molecular mechanisms, and scar reduction therapeutics Part I. The molecular basis of scar formation. J Am Acad Dermatol. 2002;66(1):1–10. https://doi.org/10.1016/j.jaad.2011.05.055.Profyris C, Tziotzios C, Do Vale I. Cutaneous scarring: Pathophysiology, molecular mechanisms, and scar reduction therapeutics Part I. The molecular basis of scar formation. J Am Acad Dermatol. 2002;66(1):1–10. https://doi.org/10.1016/j.jaad.2011.05.055.Landén NX, Li D, Ståhle M. Transition from inflammation to proliferation: a critical step during wound healing. Cell Mol Life Sci. 2016;73:3861–3885. https://doi.org/Landén NX, Li D, Ståhle M. Transition from inflammation to proliferation: a critical step during wound healing. Cell Mol Life Sci. 2016;73:3861–3885. https://doi.org/Laurent P, Jolivel V, Manicki P, et al.Immune-mediated repair: A matter of plasticity. Front Immunol. 2017;8(20):1–8. https://doi.org/10.1007/s00018-016-2268-0.Laurent P, Jolivel V, Manicki P, et al.Immune-mediated repair: A matter of plasticity. Front Immunol. 2017;8(20):1–8. https://doi.org/10.1007/s00018-016-2268-0.Sidgwick GP, Bayat A. Extracellular matrix molecules implicated in hypertrophic and keloid scarring. J Eur Acad Dermatol Venereol. 2012;26(2):141–152. https://doi.org/10.1111/j.1468-3083.2011.04200.x.Sidgwick GP, Bayat A. Extracellular matrix molecules implicated in hypertrophic and keloid scarring. J Eur Acad Dermatol Venereol. 2012;26(2):141–152. https://doi.org/10.1111/j.1468-3083.2011.04200.x.Darby IA, Laverdet B, Bonté F, Desmoulière A. Fibroblasts and myofibroblasts in wound healing. Clin Cosmet Investig Dermatol. 2014;7:301–311. https://doi.org/10.2147/CCID.S50046.Darby IA, Laverdet B, Bonté F, Desmoulière A. Fibroblasts and myofibroblasts in wound healing. Clin Cosmet Investig Dermatol. 2014;7:301–311. https://doi.org/10.2147/CCID.S50046.Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol. 2019;214(2):199–210. https://doi.org/10.1002/path.2277.Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol. 2019;214(2):199–210. https://doi.org/10.1002/path.2277.Bhogal RK, Stoica CM, McGaha TL, Bona CA. Molecular aspects of regulation of collagen gene expression in fibrosis. J Clin Immunol. 2005;25(6):592–603. https://doi.org/10.1007/s10875-005-7827-3.Bhogal RK, Stoica CM, McGaha TL, Bona CA. Molecular aspects of regulation of collagen gene expression in fibrosis. J Clin Immunol. 2005;25(6):592–603. https://doi.org/10.1007/s10875-005-7827-3.Marshall CD, Hu MS, Leavitt T, Barnes LA, Lorenz HP, Longaker MT. Cutaneous Scarring: Basic Science, Current Treatments, and Future Directions. Adv Wound Care. 2018;7(2):29–45. https://doi.org/10.1089/wound.2016.0696.Marshall CD, Hu MS, Leavitt T, Barnes LA, Lorenz HP, Longaker MT. Cutaneous Scarring: Basic Science, Current Treatments, and Future Directions. Adv Wound Care. 2018;7(2):29–45. https://doi.org/10.1089/wound.2016.0696.Wynn TA, Ramalingam TR. Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat Med. 2012;18(7):1028–1040. https://doi.org/10.1038/nm.2807.Wynn TA, Ramalingam TR. Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat Med. 2012;18(7):1028–1040. https://doi.org/10.1038/nm.2807.Jagdeo J, Shumaker PR. Traumatic Scarring. JAMA Dermatol. 2017;153(3):364. https://doi.org/10.1001/jamadermatol.2016.5232.Jagdeo J, Shumaker PR. Traumatic Scarring. JAMA Dermatol. 2017;153(3):364. https://doi.org/10.1001/jamadermatol.2016.5232.Luzina IG, Atamas SP. Fibrotic Skin Diseases. In: Gaspari A, Tyring S (eds.). Clinical and Basic Immunodermatology. Springer London; 2008.Luzina IG, Atamas SP. Fibrotic Skin Diseases. In: Gaspari A, Tyring S (eds.). Clinical and Basic Immunodermatology. Springer London; 2008.Nguyen JK, Austin E, Huang A, Mamalis A, Jagdeo J. The IL-4/IL-13 axis in skin fibrosis and scarring: mechanistic concepts and therapeutic targets. Arch Dermatol Res. 2020;312(2):81–92. https://doi.org/10.1007/s00403-019-01972-3.Nguyen JK, Austin E, Huang A, Mamalis A, Jagdeo J. The IL-4/IL-13 axis in skin fibrosis and scarring: mechanistic concepts and therapeutic targets. Arch Dermatol Res. 2020;312(2):81–92. https://doi.org/10.1007/s00403-019-01972-3.Huang X-L, Wang Y-J, Yan J-W, Wan YN, Chen B, Li BZ et al. Role of antiinflammatory cytokines IL-4 and IL-13 in systemic sclerosis. Inflamm Res. 2015;64(3-4):151–159. https://doi.org/10.1007/s00011-015-0806-0.Huang X-L, Wang Y-J, Yan J-W, Wan YN, Chen B, Li BZ et al. Role of antiinflammatory cytokines IL-4 and IL-13 in systemic sclerosis. Inflamm Res. 2015;64(3-4):151–159. https://doi.org/10.1007/s00011-015-0806-0.Oriente A, Fedarko NS, Pacocha SE, Huang SK, Lichtenstein LM, Essayan DM. Interleukin-13 modulates collagen homeostasis in human skin and keloid fibroblasts. J Pharmacol Exp Ther. 2000;292(3):988–994. Available at: https://pubmed.ncbi.nlm.nih.gov/10688614.Oriente A, Fedarko NS, Pacocha SE, Huang SK, Lichtenstein LM, Essayan DM. Interleukin-13 modulates collagen homeostasis in human skin and keloid fibroblasts. J Pharmacol Exp Ther. 2000;292(3):988–994. Available at: https://pubmed.ncbi.nlm.nih.gov/10688614.Zhu Z, Ding J, Shankowsky HA, Tredget EE. The molecular mechanism of hypertrophic scar. J Cell Commun Signal. 2012;7(4):239–252. https://doi.org/10.1007/s12079-013-0195-5.Zhu Z, Ding J, Shankowsky HA, Tredget EE. The molecular mechanism of hypertrophic scar. J Cell Commun Signal. 2012;7(4):239–252. https://doi.org/10.1007/s12079-013-0195-5.Oh S, Lee JH, Kim HM, Batsukh S, Sung MJ, Lim TH et al. Poly-L-Lactic Acid Fillers Improved Dermal Collagen Synthesis by Modulating M2 Macrophage Polarization in Aged Animal Skin. Cells. 2023;12(9):1320. https://doi.org/10.3390/cells12091320.Oh S, Lee JH, Kim HM, Batsukh S, Sung MJ, Lim TH et al. Poly-L-Lactic Acid Fillers Improved Dermal Collagen Synthesis by Modulating M2 Macrophage Polarization in Aged Animal Skin. Cells. 2023;12(9):1320. https://doi.org/10.3390/cells12091320.Stein P, Vitavska O, Kind P, Hoppe W, Wieczorek H, Schürer NY. The biological basis for poly-L-lactic acid-induced augmentation. J Dermatol Sci. 2015;78(1):26–33. https://doi.org/10.1016/j.jdermsci.2015.01.012.Stein P, Vitavska O, Kind P, Hoppe W, Wieczorek H, Schürer NY. The biological basis for poly-L-lactic acid-induced augmentation. J Dermatol Sci. 2015;78(1):26–33. https://doi.org/10.1016/j.jdermsci.2015.01.012.Duggan S, Essig F, Hünniger K, Mokhtari Z, Bauer L, Lehnert T et al. Neutrophil activation by Candida glabrata but not Candida albicans promotes fungal uptake by monocytes. Cell Microbiol. 2015;17(9):1259–1276. https://doi.org/10.1111/cmi.12443.Duggan S, Essig F, Hünniger K, Mokhtari Z, Bauer L, Lehnert T et al. Neutrophil activation by Candida glabrata but not Candida albicans promotes fungal uptake by monocytes. Cell Microbiol. 2015;17(9):1259–1276. https://doi.org/10.1111/cmi.12443.Reedy JL, Negoro PE, Feliu M, Lord AK, Khan NS, Lukason DP et al. The carbohydrate lectin receptor dectin-1 mediates the immune response to exserohilum rostratum. Infect Immun. 2017;85(3):e00903–e00916. https://doi.org/10.1128/IAI.00903-16.Reedy JL, Negoro PE, Feliu M, Lord AK, Khan NS, Lukason DP et al. The carbohydrate lectin receptor dectin-1 mediates the immune response to exserohilum rostratum. Infect Immun. 2017;85(3):e00903–e00916. https://doi.org/10.1128/IAI.00903-16.Heung LJ. Monocytes and the host response to fungal pathogens. Front Cell Infect Microbiol. 2020;10:34. https://doi.org/10.3389/fcimb.2020.00034.Heung LJ. Monocytes and the host response to fungal pathogens. Front Cell Infect Microbiol. 2020;10:34. https://doi.org/10.3389/fcimb.2020.00034.Suzuki K, Meguro K, Nakagomi D, Nakajima H. Roles of alternatively activated M2 macrophages in allergic contact dermatitis. Allergol Int. 2017;66(3):392–397. https://doi.org/10.1016/j.alit.2017.02.015.Suzuki K, Meguro K, Nakagomi D, Nakajima H. Roles of alternatively activated M2 macrophages in allergic contact dermatitis. Allergol Int. 2017;66(3):392–397. https://doi.org/10.1016/j.alit.2017.02.015.Ma P-F, Gao C-C, Yi J, Zhao J-L, Liang S-Q, Zhao Y et al. Cytotherapy with M1-polarized macrophages ameliorates liver fibrosis by modulating immune microenvironment in mice. J Hepatol. 2017;67(4):770–779. https://doi.org/10.1016/j.jhep.2017.05.022.Ma P-F, Gao C-C, Yi J, Zhao J-L, Liang S-Q, Zhao Y et al. Cytotherapy with M1-polarized macrophages ameliorates liver fibrosis by modulating immune microenvironment in mice. J Hepatol. 2017;67(4):770–779. https://doi.org/10.1016/j.jhep.2017.05.022.Oh S, Rho N-K, Byun K-A, Yang JY, Sun HJ, Jang M et al. Combined treatment of monopolar and bipolar radiofrequency increases skin elasticity by decreasing the accumulation of advanced glycated end products in aged animal skin. Int J Mol Sci. 2022;23(6):2993. https://doi.org/10.3390/ijms23062993.Oh S, Rho N-K, Byun K-A, Yang JY, Sun HJ, Jang M et al. Combined treatment of monopolar and bipolar radiofrequency increases skin elasticity by decreasing the accumulation of advanced glycated end products in aged animal skin. Int J Mol Sci. 2022;23(6):2993. https://doi.org/10.3390/ijms23062993.

The authors declare that there are no conflicts of interest present.