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Recent Advances in Drug Delivery and Formulation

Editor-in-Chief

ISSN (Print): 2667-3878
ISSN (Online): 2667-3886

Research Article

Cytotoxic Impact of Naringenin-Loaded Solid Lipid Nanoparticles on RIN5F Pancreatic β Cells via Autophagy Blockage

In Press, (this is not the final "Version of Record"). Available online 07 August, 2024
Author(s): Pardis Mohammadi Pour, Zeinab Nouri, Dariush Ghasemi, Soraya Sajadimajd and Mohammad Hosein Farzaei*
Published on: 07 August, 2024

DOI: 10.2174/0126673878297658240804192222

Price: $95

Abstract

Background: Autophagy plays a crucial role in modulating the proliferation of cancer diseases. However, the application of Naringenin (Nar), a compound with potential benefits against these diseases, has been limited due to its poor solubility and bioavailability.

Objective: This study aimed to develop solid lipid nanoparticles (Nar-SLNs) loaded with Nar to enhance their therapeutic impact.

Methods: In vitro experiments using Rin-5F cells exposed to Nar and Nar-SLNs were carried out to investigate the protective effects of Nar and its nanoformulation against the pancreatic cancer cell line of Rin-5F.

Results: Treatment with Nar and Nar-SLN led to an increase in autophagic markers (Akt, LC3, Beclin1, and ATG genes) and a decrease in the level of miR-21. Both Nar and Nar-SLN treatments inhibited cell proliferation and reduced the expression of autophagic markers. Notably, Nar-SLNs exhibited greater efficacy compared to free Nar.

Conclusion: These findings suggest that SLNs effectively enhance the cytotoxic impact of Nar, making Nar-SLNs a promising candidate for suppressing or preventing Rin-5Fcell growth.

[1]
Owens DK, Davidson KW, Krist AH, et al. Screening for pancreatic cancer: US preventive services task force reaffirmation recommendation statement. JAMA 2019; 322(5): 438-44.
[http://dx.doi.org/10.1001/jama.2019.10232] [PMID: 31386141]
[2]
Luo W, Tao J, Zheng L, Zhang T. Current epidemiology of pancreatic cancer: Challenges and opportunities. Chin J Cancer Res 2020; 32(6): 705-19.
[http://dx.doi.org/10.21147/j.issn.1000-9604.2020.06.04] [PMID: 33446994]
[3]
Jagadeesan B, Haran PH, Praveen D, Chowdary PR, Aanandhi MV. A comprehensive review on pancreatic cancer. Res J Pharm Technol 2021; 14(1): 552-4.
[http://dx.doi.org/10.5958/0974-360X.2021.00100.1]
[4]
Hu JX, Zhao CF, Chen WB, et al. Pancreatic cancer: A review of epidemiology, trend, and risk factors. World J Gastroenterol 2021; 27(27): 4298-321.
[http://dx.doi.org/10.3748/wjg.v27.i27.4298] [PMID: 34366606]
[5]
Cheng Jin, Ling Bai. Pancreatic cancer: Current situation and challenges. Gastroenterol Hepatol Lett 2020; 2(1): 1-3.
[http://dx.doi.org/10.18063/ghl.v2i1.243]
[6]
Menini S, Iacobini C, Vitale M, Pesce C, Pugliese G. Diabetes and pancreatic cancer—A dangerous liaison relying on carbonyl stress. Cancers 2021; 13(2): 313.
[http://dx.doi.org/10.3390/cancers13020313] [PMID: 33467038]
[7]
Liang JQ, Teoh N, Xu L, et al. Dietary cholesterol promotes steatohepatitis related hepatocellular carcinoma through dysregulated metabolism and calcium signaling. Nat Commun 2018; 9(1): 4490.
[http://dx.doi.org/10.1038/s41467-018-06931-6] [PMID: 30367044]
[8]
Klionsky DJ, Emr SD. Autophagy as a regulated pathway of cellular degradation. Science 2000; 290(5497): 1717-21.
[http://dx.doi.org/10.1126/science.290.5497.1717] [PMID: 11099404]
[9]
Ebato C, Uchida T, Arakawa M, et al. Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat diet. Cell Metab 2008; 8(4): 325-32.
[http://dx.doi.org/10.1016/j.cmet.2008.08.009] [PMID: 18840363]
[10]
Boya P. González-Polo RA, Casares N, et al. Inhibition of macroautophagy triggers apoptosis. Mol Cell Biol 2005; 25(3): 1025-40.
[http://dx.doi.org/10.1128/MCB.25.3.1025-1040.2005] [PMID: 15657430]
[11]
Tsujimoto Y, Shimizu S. Another way to die: Autophagic programmed cell death. Cell Death Differ 2005; 12 (Suppl. 2): 1528-34.
[http://dx.doi.org/10.1038/sj.cdd.4401777] [PMID: 16247500]
[12]
Eltschinger S, Loewith R. TOR complexes and the maintenance of cellular homeostasis. Trends Cell Biol 2016; 26(2): 148-59.
[http://dx.doi.org/10.1016/j.tcb.2015.10.003] [PMID: 26546292]
[13]
Levine B, Kroemer G. SnapShot: Macroautophagy. Cell Death Differ 2008; 132(1): 162.
[http://dx.doi.org/10.1016/j.cell.2007.12.026]
[14]
Lim YM, Lim H, Hur KY, et al. Systemic autophagy insufficiency compromises adaptation to metabolic stress and facilitates progression from obesity to diabetes. Nat Commun 2014; 5(1): 4934.
[http://dx.doi.org/10.1038/ncomms5934] [PMID: 25255859]
[15]
Shibata M, Yoshimura K, Furuya N, et al. The MAP1-LC3 conjugation system is involved in lipid droplet formation. Biochem Biophys Res Commun 2009; 382(2): 419-23.
[http://dx.doi.org/10.1016/j.bbrc.2009.03.039] [PMID: 19285958]
[16]
Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American college of rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol 2016; 68(1): 1-26.
[http://dx.doi.org/10.1002/art.39480] [PMID: 26545940]
[17]
Zhang Y, Goldman S, Baerga R, Zhao Y, Komatsu M, Jin S. Adipose-specific deletion of autophagy-related gene 7 (atg7) in mice reveals a role in adipogenesis. Proc Natl Acad Sci USA 2009; 106(47): 19860-5.
[http://dx.doi.org/10.1073/pnas.0906048106] [PMID: 19910529]
[18]
Deshpande S, Abdollahi M, Wang M, Lanting L, Kato M, Natarajan R. Reduced autophagy by a microRNA-mediated signaling cascade in diabetes-induced renal glomerular hypertrophy. Sci Rep 2018; 8(1): 6954.
[http://dx.doi.org/10.1038/s41598-018-25295-x] [PMID: 29725042]
[19]
Estrella S, Garcia-Diaz DF, Codner E, Camacho-Guillén P, Pérez-Bravo F. Expression of miR-22 and miR-150 in type 1 diabetes mellitus: Possible relationship with autoimmunity and clinical characteristics. J Medicina Clínica 2016; 147(6): 245-7.
[PMID: 27377214]
[20]
Madhyastha R, Madhyastha H, Nakajima Y, Omura S, Maruyama M. MicroRNA signature in diabetic wound healing: Promotive role of miR‐21 in fibroblast migration. Int Wound J 2012; 9(4): 355-61.
[http://dx.doi.org/10.1111/j.1742-481X.2011.00890.x] [PMID: 22067035]
[21]
Olivieri F, Spazzafumo L, Bonafè M, et al. MiR-21-5p and miR-126a-3p levels in plasma and circulating angiogenic cells: Relationship with type 2 diabetes complications. Oncotarget 2015; 6(34): 35372-82.
[PMID: 26498351]
[22]
Zhong X, Chung ACK, Chen HY, et al. miR-21 is a key therapeutic target for renal injury in a mouse model of type 2 diabetes. Diabetologia 2013; 56(3): 663-74.
[http://dx.doi.org/10.1007/s00125-012-2804-x] [PMID: 23292313]
[23]
Guo YB, Ji TF, Zhou HW, Yu JL. Retracted article: Effects of microRNA-21 on nerve cell regeneration and neural function recovery in diabetes mellitus combined with cerebral infarction rats by targeting pdcd4. Mol Neurobiol 2018; 55(3): 2494-505.
[http://dx.doi.org/10.1007/s12035-017-0484-8] [PMID: 28389999]
[24]
Zhang Y. MicroRNA-22 promotes renal tubulointerstitial fibrosis by targeting PTEN and suppressing autophagy in diabetic nephropathy. J Diabetes Res 2018; 2018: 4728645.
[25]
Chen Z, Li YB, Han J, et al. The double-edged effect of autophagy in pancreatic beta cells and diabetes. Autophagy 2011; 7(1): 12-6.
[http://dx.doi.org/10.4161/auto.7.1.13607] [PMID: 20935505]
[26]
Yang LC, Hsieh CC, Wen CL, Chiu CH, Lin WC. Structural characterization of an immunostimulating polysaccharide from the stems of a new medicinal Dendrobium species: Dendrobium Taiseed Tosnobile. Int J Biol Macromol 2017; 103: 1185-93.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.05.185] [PMID: 28579460]
[27]
Hidayat AFA, Chan CK, Mohamad J, Kadir HA. Leptospermum flavescens Sm. Protect pancreatic β cell function from streptozotocin involving apoptosis and autophagy signaling pathway in in vitro and in vivo case study. J Ethnopharmacol 2018; 226: 120-31.
[http://dx.doi.org/10.1016/j.jep.2018.08.020] [PMID: 30118836]
[28]
Varshney R, Gupta S, Roy P. Cytoprotective effect of kaempferol against palmitic acid-induced pancreatic β-cell death through modulation of autophagy via AMPK/mTOR signaling pathway. Mol Cell Endocrinol 2017; 448: 1-20.
[http://dx.doi.org/10.1016/j.mce.2017.02.033] [PMID: 28237721]
[29]
Fattahi A, Niyazi F, Shahbazi B, Farzaei MH, Bahrami G. Antidiabetic mechanisms of Rosa canina fruits: An in vitro evaluation. J Evid Based Complementary Altern Med 2017; 22(1): 127-33.
[http://dx.doi.org/10.1177/2156587216655263] [PMID: 27352916]
[30]
Nouri Z, Fakhri S, El-Senduny FF, et al. On the neuroprotective effects of naringenin: Pharmacological targets, signaling pathways, molecular mechanisms, and clinical perspective. Biomolecules 2019; 9(11): 690.
[http://dx.doi.org/10.3390/biom9110690] [PMID: 31684142]
[31]
Nouri Z, Hajialyani M, Izadi Z, Bahramsoltani R, Farzaei MH, Abdollahi M. Nanophytomedicines for the prevention of metabolic syndrome: A pharmacological and biopharmaceutical review. Front Bioeng Biotechnol 2020; 8: 425.
[http://dx.doi.org/10.3389/fbioe.2020.00425] [PMID: 32478050]
[32]
Mishra V, Bansal KK, Verma A, et al. Solid lipid nanoparticles: Emerging colloidal nano drug delivery systems. Pharmaceutics 2018; 10(4): 191.
[http://dx.doi.org/10.3390/pharmaceutics10040191] [PMID: 30340327]
[33]
Ji P, Yu T, Liu Y, et al. Naringenin-loaded solid lipid nanoparticles: Preparation, controlled delivery, cellular uptake, and pulmonary pharmacokinetics. Drug Des Devel Ther 2016; 10: 911-25.
[PMID: 27041995]
[34]
Nouri Z, Sajadimajd S, Hoseinzadeh L, et al. Neuroprotective effect of naringenin‐loaded solid lipid nanoparticles against streptozocin‐induced neurotoxicity through autophagy blockage. J Food Biochem 2022; 46(12): e14408.
[http://dx.doi.org/10.1111/jfbc.14408] [PMID: 36129161]
[35]
Ahmadifard Z, Ahmeda A, Rasekhian M, Moradi S, Arkan E. Chitosan-coated magnetic solid lipid nanoparticles for controlled release of letrozole. J Drug Deliv Sci Technol 2020; 57: 101621.
[http://dx.doi.org/10.1016/j.jddst.2020.101621]
[36]
Sajadimajd S, Bahrami G, Mohammadi B, Nouri Z, Farzaei MH, Chen JT. Protective effect of the isolated oligosaccharide from Rosa canina in STZ‐treated cells through modulation of the autophagy pathway. J Food Biochem 2020; 44(10): e13404.
[http://dx.doi.org/10.1111/jfbc.13404] [PMID: 32761921]
[37]
Vistica DT, Skehan P, Scudiero D, Monks A, Pittman A, Boyd MR. Tetrazolium-based assays for cellular viability: A critical examination of selected parameters affecting formazan production. Cancer Res 1991; 51(10): 2515-20.
[PMID: 2021931]
[38]
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Δ Δ C(T)) method. Methods 2001; 25(4): 402-8.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[39]
Hashemi M, Mirdamadi MSA, Talebi Y, et al. Pre-clinical and clinical importance of miR-21 in human cancers: Tumorigenesis, therapy response, delivery approaches and targeting agents. Pharmacol Res 2023; 187: 106568.
[http://dx.doi.org/10.1016/j.phrs.2022.106568] [PMID: 36423787]
[40]
Zhao Q, Chen S, Zhu Z, et al. miR-21 promotes EGF-induced pancreatic cancer cell proliferation by targeting Spry2. Cell Death Dis 2018; 9(12): 1157.
[http://dx.doi.org/10.1038/s41419-018-1182-9] [PMID: 30464258]
[41]
Sui X, Chen R, Wang Z, et al. Autophagy and chemotherapy resistance: A promising therapeutic target for cancer treatment. Cell Death Dis 2013; 4(10): e838-8.
[http://dx.doi.org/10.1038/cddis.2013.350] [PMID: 24113172]
[42]
Tracey N, Creedon H, Kemp AJ, et al. HO-1 drives autophagy as a mechanism of resistance against HER2-targeted therapies. Breast Cancer Res Treat 2020; 179(3): 543-55.
[http://dx.doi.org/10.1007/s10549-019-05489-1] [PMID: 31705351]
[43]
Clark CA, Gupta HB, Curiel TJ. Tumor cell-intrinsic CD274/PD-L1: A novel metabolic balancing act with clinical potential. Autophagy 2017; 13(5): 987-8.
[http://dx.doi.org/10.1080/15548627.2017.1280223] [PMID: 28368722]
[44]
Qu X, Yu J, Bhagat G, et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest 2003; 112(12): 1809-20.
[http://dx.doi.org/10.1172/JCI20039] [PMID: 14638851]
[45]
Yue Z, Jin S, Yang C, Levine AJ, Heintz N. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci USA 2003; 100(25): 15077-82.
[http://dx.doi.org/10.1073/pnas.2436255100] [PMID: 14657337]
[46]
Takamura A, Komatsu M, Hara T, et al. Autophagy-deficient mice develop multiple liver tumors. Genes Dev 2011; 25(8): 795-800.
[http://dx.doi.org/10.1101/gad.2016211] [PMID: 21498569]
[47]
Jung YY, Lee YK, Koo JS. The potential of Beclin 1 as a therapeutic target for the treatment of breast cancer. Expert Opin Ther Targets 2016; 20(2): 167-78.
[http://dx.doi.org/10.1517/14728222.2016.1085971] [PMID: 26357854]
[48]
Yang S, Wang X, Contino G, et al. Pancreatic cancers require autophagy for tumor growth. Genes Dev 2011; 25(7): 717-29.
[http://dx.doi.org/10.1101/gad.2016111] [PMID: 21406549]
[49]
Algul D, Duman G, Ozdemir S, Acar ET, Yener G. Preformulation, characterization, and in vitro release studies of caffeine-loaded solid lipid nanoparticles. J Cosmet Sci 2018; 69(3): 165-73.
[PMID: 30052191]
[50]
Hu F, Hong Y, Yuan H. Preparation and characterization of solid lipid nanoparticles containing peptide. Int J Pharm 2004; 273(1-2): 29-35.
[http://dx.doi.org/10.1016/j.ijpharm.2003.12.016] [PMID: 15010127]
[51]
Bollimpelli VS, Kumar P, Kumari S, Kondapi AK. Neuroprotective effect of curcumin-loaded lactoferrin nano particles against rotenone induced neurotoxicity. Neurochem Int 2016; 95: 37-45.
[http://dx.doi.org/10.1016/j.neuint.2016.01.006] [PMID: 26826319]
[52]
Brunet A, Bonni A, Zigmond MJ, et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 1999; 96(6): 857-68.
[http://dx.doi.org/10.1016/S0092-8674(00)80595-4] [PMID: 10102273]
[53]
John A, Raza H. Azadirachtin attenuates lipopolysaccharide-induced ROS production, DNA damage, and apoptosis by regulating JNK/Akt and AMPK/mTOR-dependent pathways in Rin-5F pancreatic beta cells. Biomedicines 2021; 9(12): 1943.
[PMID: 34944759]
[54]
Huo D, Jiang S, Qin Z, et al. Omethoate induces pharyngeal cancer cell proliferation and G1/S cell cycle progression by activation of Akt/GSK-3β/cyclin D1 signaling pathway. Toxicology 2019; 427: 152298.
[http://dx.doi.org/10.1016/j.tox.2019.152298] [PMID: 31574243]
[55]
Martindale JL, Holbrook NJ. Cellular response to oxidative stress: Signaling for suicide and survival. J Cell Physiol 2002; 192(1): 1-15.
[http://dx.doi.org/10.1002/jcp.10119] [PMID: 12115731]
[56]
Jiang P, Mizushima N. Autophagy and human diseases. Cell Res 2014; 24(1): 69-79.
[http://dx.doi.org/10.1038/cr.2013.161] [PMID: 24323045]
[57]
Ornatowski W, Lu Q, Yegambaram M, et al. Complex interplay between autophagy and oxidative stress in the development of pulmonary disease. Redox Biol 2020; 36: 101679.
[http://dx.doi.org/10.1016/j.redox.2020.101679] [PMID: 32818797]
[58]
Chen X, Li L, Xu S, et al. Ultraviolet B radiation down-regulates ULK1 and ATG7 expression and impairs the autophagy response in human keratinocytes. J Photochem Photobiol B 2018; 178: 152-64.
[http://dx.doi.org/10.1016/j.jphotobiol.2017.08.043] [PMID: 29154199]
[59]
Madrigal-Matute J, Cuervo AM. Regulation of liver metabolism by autophagy. Gastroenterology 2016; 150(2): 328-39.
[http://dx.doi.org/10.1053/j.gastro.2015.09.042] [PMID: 26453774]
[60]
Yang Y, Fiskus W, Yong B, et al. Acetylated hsp70 and KAP1-mediated Vps34 SUMOylation is required for autophagosome creation in autophagy. Proc Natl Acad Sci USA 2013; 110(17): 6841-6.
[http://dx.doi.org/10.1073/pnas.1217692110] [PMID: 23569248]
[61]
Yang K, Cao F, Wang W, Tian Z, Yang L. The relationship between HMGB1 and autophagy in the pathogenesis of diabetes and its complications. Front Endocrinol 2023; 14: 1141516.
[http://dx.doi.org/10.3389/fendo.2023.1141516] [PMID: 37065747]
[62]
Essick EE, Sam F. Oxidative stress and autophagy in cardiac disease, neurological disorders, aging and cancer. Oxid Med Cell Longev 2010; 3(3): 168-77.
[http://dx.doi.org/10.4161/oxim.3.3.12106] [PMID: 20716941]
[63]
Brimson JM, Prasanth MI, Malar DS, et al. Plant polyphenols for aging health: Implication from their autophagy modulating properties in age-associated diseases. Pharmaceuticals 2021; 14(10): 982.
[http://dx.doi.org/10.3390/ph14100982] [PMID: 34681206]
[64]
Wang Z, Quan W, Zeng M, et al. Regulation of autophagy by plant‐based polyphenols: A critical review of current advances in glucolipid metabolic diseases and food industry applications. Food Front 2023; 4(3): 1039-67.
[http://dx.doi.org/10.1002/fft2.255]
[65]
Barth S, Glick D, Macleod KF. Autophagy: Assays and artifacts. J Pathol 2010; 221(2): 117-24.
[http://dx.doi.org/10.1002/path.2694] [PMID: 20225337]
[66]
Hsu CP, Oka S, Shao D, Hariharan N, Sadoshima J. Nicotinamide phosphoribosyltransferase regulates cell survival through NAD+ synthesis in cardiac myocytes. Circ Res 2009; 105(5): 481-91.
[http://dx.doi.org/10.1161/CIRCRESAHA.109.203703] [PMID: 19661458]
[67]
Salminen A, Kaarniranta K. SIRT1: Regulation of longevity via autophagy. Cell Signal 2009; 21(9): 1356-60.
[http://dx.doi.org/10.1016/j.cellsig.2009.02.014] [PMID: 19249351]
[68]
Magura J, Hassan D, Moodley R, Mackraj I. Hesperidin-loaded nanoemulsions improve cytotoxicity, induce apoptosis, and downregulate miR-21 and miR-155 expression in MCF-7. J Microencapsul 2021; 38(7-8): 486-95.
[http://dx.doi.org/10.1080/02652048.2021.1979673] [PMID: 34510994]
[69]
Fahmy AM, Labonté P. The autophagy elongation complex (ATG5-12/16L1) positively regulates HCV replication and is required for wild-type membranous web formation. Sci Rep 2017; 7(1): 40351.
[http://dx.doi.org/10.1038/srep40351] [PMID: 28067309]
[70]
Chen J, Zhang L, Zhou H, et al. Inhibition of autophagy promotes cisplatin-induced apoptotic cell death through Atg5 and Beclin 1 in A549 human lung cancer cells. Mol Med Rep 2018; 17(5): 6859-65.
[http://dx.doi.org/10.3892/mmr.2018.8686] [PMID: 29512762]
[71]
Ustuner D, Kolac UK, Ustuner MC, et al. Naringenin ameliorate carbon tetrachloride-induced hepatic damage through inhibition of endoplasmic reticulum stress and autophagy in rats. J Med Food 2020; 23(11): 1192-200.
[http://dx.doi.org/10.1089/jmf.2019.0265] [PMID: 32125927]
[72]
Xu Z, Han X, Ou D, et al. Targeting PI3K/AKT/mTOR-mediated autophagy for tumor therapy. Appl Microbiol Biotechnol 2020; 104(2): 575-87.
[http://dx.doi.org/10.1007/s00253-019-10257-8] [PMID: 31832711]
[73]
Wang X, Jiang Y, Zhu L, et al. Autophagy protects PC12 cells against deoxynivalenol toxicity via the class III PI3K/beclin 1/Bcl‐2 pathway. J Cell Physiol 2020; 235(11): 7803-15.
[http://dx.doi.org/10.1002/jcp.29433] [PMID: 31930515]
[74]
Xu L, Shen J, Yu L, et al. Role of autophagy in sevoflurane-induced neurotoxicity in neonatal rat hippocampal cells. Brain Res Bull 2018; 140: 291-8.
[http://dx.doi.org/10.1016/j.brainresbull.2018.05.020] [PMID: 29857124]
[75]
Eisenberg-Lerner A, Bialik S, Simon H-U, Kimchi A. Life and death partners: Apoptosis, autophagy and the cross-talk between them. Cell Death Differ 2009; 16(7): 966-75.
[http://dx.doi.org/10.1038/cdd.2009.33] [PMID: 19325568]
[76]
Gao Y, Li J, Wu L, et al. Tetrahydrocurcumin provides neuroprotection in rats after traumatic brain injury: Autophagy and the PI3K/AKT pathways as a potential mechanism. J Surg Res 2016; 206(1): 67-76.
[http://dx.doi.org/10.1016/j.jss.2016.07.014] [PMID: 27916377]
[77]
Li Y, Cho MH, Lee SS, Lee DE, Cheong H, Choi Y. Hydroxychloroquine-loaded hollow mesoporous silica nanoparticles for enhanced autophagy inhibition and radiation therapy. J Control Release 2020; 325: 100-10.
[http://dx.doi.org/10.1016/j.jconrel.2020.06.025] [PMID: 32621826]
[78]
Bai Y, Su X, Piao L, Jin Z, Jin R. Involvement of astrocytes and microRNA dysregulation in neurodegenerative diseases: From pathogenesis to therapeutic potential. Front Mol Neurosci 2021; 14: 556215.
[http://dx.doi.org/10.3389/fnmol.2021.556215] [PMID: 33815055]
[79]
Yu X, Li R, Shi W, et al. Silencing of MicroRNA-21 confers the sensitivity to tamoxifen and fulvestrant by enhancing autophagic cell death through inhibition of the PI3K-AKT-mTOR pathway in breast cancer cells. Biomed Pharmacother 2016; 77: 37-44.
[http://dx.doi.org/10.1016/j.biopha.2015.11.005] [PMID: 26796263]
[80]
Meng X, Zhang Y, Huang XR, Ren G, Li J, Lan HY. Treatment of renal fibrosis by rebalancing TGF-β/Smad signaling with the combination of asiatic acid and naringenin. Oncotarget 2015; 6(35): 36984-97.
[http://dx.doi.org/10.18632/oncotarget.6100] [PMID: 26474462]
[81]
Shi LB, Tang PF, Zhang W, Zhao YP, Zhang LC, Zhang H. Naringenin inhibits spinal cord injury-induced activation of neutrophils through miR-223. Gene 2016; 592(1): 128-33.
[http://dx.doi.org/10.1016/j.gene.2016.07.037] [PMID: 27432064]

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