Nedeva, C. et al. TREML4 receptor regulates inflammation and innate immune cell death during polymicrobial sepsis. Nat. Immunol. 21(12), 1585–1596. https://doi.org/10.1038/s41590-020-0789-z (2020).
Singer, M. et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315(8), 801–810 (2016).
Srzić, I., Nesek Adam, V. & Tunjić Pejak, D. Sepsis definition: What’s new in the treatment guidelines. Acta Clin. Croat. 61(Suppl 1), 67–72. https://doi.org/10.20471/acc.2022.61.s1.11 (2022).
Rudd, K. E. et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: Analysis for the Global Burden of Disease Study. Lancet 395(10219), 200–211. https://doi.org/10.1016/s0140-6736(19)32989-7 (2020).
Shappell, C. N., Klompas, M. & Rhee, C. Surveillance strategies for tracking sepsis incidence and outcomes. J. Infect. Dis. 222(Suppl 2), S74-s83. https://doi.org/10.1093/infdis/jiaa102 (2020).
Hoste, E. A. et al. Epidemiology of acute kidney injury in critically ill patients: The multinational AKI-EPI study. Intensive Care Med. 41(8), 1411–1423. https://doi.org/10.1007/s00134-015-3934-7 (2015).
Uchino, S. et al. Acute renal failure in critically ill patients: A multinational, multicenter study. JAMA 294(7), 813–818. https://doi.org/10.1001/jama.294.7.813 (2005).
Thakar, C. V., Christianson, A., Freyberg, R., Almenoff, P. & Render, M. L. Incidence and outcomes of acute kidney injury in intensive care units: A Veterans Administration study. Crit. Care Med. 37(9), 2552–2558. https://doi.org/10.1097/CCM.0b013e3181a5906f (2009).
Ruiz-Ortega, M., Rayego-Mateos, S., Lamas, S., Ortiz, A. & Rodrigues-Diez, R. R. Targeting the progression of chronic kidney disease. Nat. Rev. Nephrol. 16(5), 269–288. https://doi.org/10.1038/s41581-019-0248-y (2020).
Wang, W., Koka, V. & Lan, H. Y. Transforming growth factor-beta and Smad signalling in kidney diseases. Nephrology (Carlton) 10(1), 48–56. https://doi.org/10.1111/j.1440-1797.2005.00334.x (2005).
Fathy, M., Okabe, M., Saad Eldien, H. M. & Yoshida, T. AT-MSCs antifibrotic activity is improved by eugenol through modulation of TGF-beta/smad signaling pathway in rats. Molecules 25(2), 1. https://doi.org/10.3390/molecules25020348 (2020).
Hewlett, J. C., Kropski, J. A. & Blackwell, T. S. Idiopathic pulmonary fibrosis: Epithelial-mesenchymal interactions and emerging therapeutic targets. Matrix Biol. 71–72, 112–127. https://doi.org/10.1016/j.matbio.2018.03.021 (2018).
Alaaeldin, R., Abuo-Rahma, G. E. A., Zhao, Q. L. & Fathy, M. Modulation of apoptosis and epithelial-mesenchymal transition E-cadherin/TGF-beta/Snail/TWIST pathways by a new ciprofloxacin chalcone in breast cancer cells. Anticancer Res. 41(5), 2383–2395. https://doi.org/10.21873/anticanres.15013 (2021).
Isaka, Y. Targeting TGF-β signaling in kidney fibrosis. Int. J. Mol. Sci. 19(9), 2532 (2018).
Németh, Á., Mózes, M. M., Calvier, L., Hansmann, G. & Kökény, G. The PPARγ agonist pioglitazone prevents TGF-β induced renal fibrosis by repressing EGR-1 and STAT3. BMC Nephrol. 20(1), 245. https://doi.org/10.1186/s12882-019-1431-x (2019).
Bekhit, A. A., Beshay, O. N., Fawzy, M. A. & Abdel-Hafez, S. M. N. Curative effect of AD-MSCs against cisplatin-induced hepatotoxicity in rats is potentiated by azilsartan: targeting oxidative stress, MAPK, and apoptosis signaling pathways. Stem Cells Int. 6767, 735. https://doi.org/10.1155/2023/6767735 (2023).
Fawzy, M. A., Maher, S. A., Bakkar, S. M., El-Rehany, M. A. & Fathy, M. Pantoprazole attenuates MAPK (ERK1/2, JNK, p38)-NF-kappaB and apoptosis signaling pathways after renal ischemia/reperfusion injury in rats. Int. J. Mol. Sci. 22(19), 10669. https://doi.org/10.3390/ijms221910669 (2021).
Fawzy, M. A., Nasr, G., Ali, F. E. M. & Fathy, M. Quercetin potentiates the hepatoprotective effect of sildenafil and/or pentoxifylline against intrahepatic cholestasis: Role of Nrf2/ARE, TLR4/NF-κB, and NLRP3/IL-1β signaling pathways. Life Sci. 314, 121343. https://doi.org/10.1016/j.lfs.2022.121343 (2023).
Abdellatef, A. A. et al. Inhibition of cell-intrinsic NF-kappaB activity and metastatic abilities of breast cancer by aloe-emodin and emodic-acid isolated from Asphodelus microcarpus. J. Nat. Med. 75(4), 840–853. https://doi.org/10.1007/s11418-021-01526-w (2021).
Alaaeldin, R. et al. A new EGFR inhibitor from ficus benghalensis exerted potential anti-inflammatory activity via Akt/PI3K pathway inhibition. Curr. Issues Mol. Biol. 44(7), 2967–2981. https://doi.org/10.3390/cimb44070205 (2022).
Fawzy, M. A. et al. Vincamine modulates the effect of pantoprazole in renal ischemia/reperfusion injury by attenuating MAPK and apoptosis signaling pathways. Molecules 27(4), 1383. https://doi.org/10.3390/molecules27041383 (2022).
Fathy, M. et al. A new ciprofloxacin-derivative inhibits proliferation and suppresses the migration ability of HeLa cells. Anticancer Res. 40(9), 5025–5033 (2020).
Mohyeldin, R. H. et al. LCZ696 attenuates sepsis-induced liver dysfunction in rats; the role of oxidative stress, apoptosis, and JNK1/2-P38 signaling pathways. Life Sci. 334, 122210. https://doi.org/10.1016/j.lfs.2023.122210 (2023).
Shytaj, I. L. et al. The FDA-approved drug cobicistat synergizes with remdesivir to inhibit SARS-CoV-2 replication in vitro and decreases viral titers and disease progression in syrian hamsters. mBiol. 13(2), e0370521. https://doi.org/10.1128/mbio.03705-21 (2022).
Alaaeldin, R. et al. Azilsartan modulates HMGB1/NF-kappa;B/p38/ERK1/2/JNK and apoptosis pathways during renal ischemia reperfusion injury. Cells 12(1), 185. https://doi.org/10.3390/CELLS12010185 (2023).
Sabra, R. T. et al. Russelioside A, a pregnane glycoside from Caralluma tuberculate, inhibits cell-intrinsic NF-κB activity and metastatic ability of breast cancer cells. Biol. Pharmaceut. Bull. 45(10), 1564–1571. https://doi.org/10.1248/bpb.b22-00508 (2022).
de Groot, A. A., Mathy, M. J., van Zwieten, P. A. & Peters, S. L. Antioxidant activity of nebivolol in the rat aorta. J. Cardiovasc. Pharmacol. 43(1), 148–153. https://doi.org/10.1097/00005344-200401000-00022 (2004).
Oelze, M. et al. Nebivolol inhibits superoxide formation by NADPH oxidase and endothelial dysfunction in angiotensin II-treated rats. Hypertension 48(4), 677–684. https://doi.org/10.1161/01.Hyp.0000239207.82326.29 (2006).
Wolf, S. C. et al. Major differences in gene expression in human coronary smooth muscle cells after nebivolol or metoprolol treatment. Int. J. Cardiol. 125(1), 4–10. https://doi.org/10.1016/j.ijcard.2007.02.045 (2008).
Mercanoglu, G. et al. The effects of nebivolol on apoptosis in a rat infarct model. Circ. J. 72(4), 660–670. https://doi.org/10.1253/circj.72.660 (2008).
Fink, M. P. Animal models of sepsis. Virulence 5(1), 143–153 (2014).
Bhatia, A., Saikia, P. P., Dkhar, B. & Pyngrope, H. Anesthesia protocol for ear surgery in Wistar rats (animal research). Anim. Mod. Exp. Med. 5(2), 183–188. https://doi.org/10.1002/ame2.12198 (2022).
Abdallah, O. & Sharaf Eldin, A. Nebivolol ameliorates indomethacin-induced gastric ulcer in adult albino rats: Role of inducible nitric oxide synthase. Egypt. J. For. Sci. Appl. Toxicol. 16, 147–167. https://doi.org/10.21608/ejfsat.2016.41023 (2016).
Mohamed, E. A. & Kassem, H. H. Protective effect of nebivolol on doxorubicin-induced cardiotoxicity in rats. Arch. Med. Sci. 14(6), 1450–1458. https://doi.org/10.5114/aoms.2018.79008 (2018).
Said, E. S. et al. Evaluation of hepatoprotective effect of nebivolol and sodium copper chlorophyllin on CCL4-induced hepatotoxicity in mice. Eur. Rev. Med. Pharmacol. Sci. 26(5), 1717–1728. https://doi.org/10.26355/eurrev_202203_28241 (2022).
Li, X., Li, Q., Wu, L. & Wang, Y. Nebivolol alleviates vascular endothelial insulin resistance by inhibiting endoplasmic reticulum stress. Int. Heart J. 64(2), 283–293. https://doi.org/10.1536/ihj.22-484 (2023).
Naeem, A. G., El-Naga, R. N. & Michel, H. E. Nebivolol elicits a neuroprotective effect in the cuprizone model of multiple sclerosis in mice: emphasis on M1/M2 polarization and inhibition of NLRP3 inflammasome activation. Inflammopharmacology 30(6), 2197–2209. https://doi.org/10.1007/s10787-022-01045-4 (2022).
Zhang, N. et al. Protective effects and mechanisms of high-dose vitamin C on sepsis-associated cognitive impairment in rats. Sci. Rep. 11(1), 14511. https://doi.org/10.1038/s41598-021-93861-x (2021).
Peerapornratana, S., Manrique-Caballero, C. L., Gómez, H. & Kellum, J. A. Acute kidney injury from sepsis: Current concepts, epidemiology, pathophysiology, prevention and treatment. Kidney Int. 96(5), 1083–1099. https://doi.org/10.1016/j.kint.2019.05.026 (2019).
Chaudhry, H., Zhou, J. & Zhong, Y. Role of cytokines as a double-edged sword in sepsis. In Vivo 27(6), 669–684 (2013).
Wang, H. et al. Epidemiology of sepsis-associated acute kidney injury in Beijing, China: A descriptive analysis. Int. J. Gen. Med. 14, 5631–5649. https://doi.org/10.2147/ijgm.S320768 (2021).
Wiersema, R. et al. Two subphenotypes of septic acute kidney injury are associated with different 90-day mortality and renal recovery. Crit. Care 24(1), 150. https://doi.org/10.1186/s13054-020-02866-x (2020).
Borges-Rodriguez, M. et al. Platelet inhibition prevents NLRP3 inflammasome activation and sepsis-induced kidney injury. Int. J. Mol. Sci. 22(19), 1. https://doi.org/10.3390/ijms221910330 (2021).
Jabber, H., Mohammed, B. & Hadi, N. R. Investigating the renoprotective effect of C21 in male mice with sepsis via modulation of p-AKT/PI3K expression. J. Med. Life 16(2), 203–209. https://doi.org/10.25122/jml-2022-0299 (2023).
Chen, X. et al. Klotho ameliorates sepsis-induced acute kidney injury but is irrelevant to autophagy. Oncol. Targets Ther. 11, 867–881. https://doi.org/10.2147/ott.S156891 (2018).
Guo, L.-P. et al. Effect of thymoquinone on acute kidney injury induced by sepsis in BALB/c mice. BioMed. Res. Int. 1594, 726. https://doi.org/10.1155/2020/1594726 (2020).
Abdelnaser, M., Alaaeldin, R., Attya, M. E. & Fathy, M. Modulating Nrf-2/HO-1, apoptosis and oxidative stress signaling pathways by gabapentin ameliorates sepsis-induced acute kidney injury. Naunyn Schmiedebergs Arch. Pharmacol. 397(2), 947–958. https://doi.org/10.1007/s00210-023-02650-y (2024).
Cavdar, Z. et al. Role of p38 MAPK, Akt and NFκB in renoprotective effects of nebivolol on renal ischemia-reperfusion injury in rats. Biotech. Histochem. 98(6), 401–411. https://doi.org/10.1080/10520295.2023.2212412 (2023).
Nasr, A. M., Rezq, S., Shaheen, A. & Elshazly, S. M. Renal protective effect of nebivolol in rat models of acute renal injury: Role of sodium glucose co-transporter 2. Pharmacol. Rep. 72(4), 956–968. https://doi.org/10.1007/s43440-020-00059-5 (2020).
Wanas, H. et al. Nebivolol protects against cyclophosphamide-induced nephrotoxicity through modulation of oxidative stress, inflammation, and apoptosis. Clin. Exp. Pharmacol. Physiol. 48(5), 811–819. https://doi.org/10.1111/1440-1681.13481 (2021).
Ow, C. P. C. et al. Targeting oxidative stress in septic acute kidney injury: From theory to practice. J. Clin. Med. 10(17), 1. https://doi.org/10.3390/jcm10173798 (2021).
Dröge, W. Free radicals in the physiological control of cell function. Physiol. Rev. 82(1), 47–95. https://doi.org/10.1152/physrev.00018.2001 (2002).
Biswal, S. & Remick, D. G. Sepsis: Redox mechanisms and therapeutic opportunities. Antioxid. Redox. Signal 9(11), 1959–1961. https://doi.org/10.1089/ars.2007.1808 (2007).
Son, Y., Cheong, Y. K., Kim, N. H., Chung, H. T. & Kang, D. G. Mitogen-activated protein kinases and reactive oxygen species: How can ROS activate MAPK pathways?. J. Signal Transduct. 792, 639. https://doi.org/10.1155/2011/792639 (2011).
Abdelnaser, M., Alaaeldin, R., Attya, M. E. & Fathy, M. Hepatoprotective potential of gabapentin in cecal ligation and puncture-induced sepsis; targeting oxidative stress, apoptosis, and NF-kB/MAPK signaling pathways. Life Sci. 121, 562. https://doi.org/10.1016/j.lfs.2023.121562 (2023).
Alaaeldin, R. et al. Vincamine ameliorates epithelial-mesenchymal transition in bleomycin-induced pulmonary fibrosis in rats; targeting TGF-beta/MAPK/snai1 pathway. Molecules 28(12), 1. https://doi.org/10.3390/molecules28124665 (2023).
Gu, Y.-Y., Liu, X.-S., Huang, X.-R., Yu, X.-Q. & Lan, H.-Y. Diverse role of TGF-β in kidney disease. Front. Cell Dev. Biol. 8, 1. https://doi.org/10.3389/fcell.2020.00123 (2020).
Fawzy, M. A. et al. Nephroprotective effect of AT-MSCs against cisplatin-induced EMT is improved by azilsartan via attenuating oxidative stress and TGF-β/Smad signaling. Biomed. Pharmacother. 158(6), 114097. https://doi.org/10.1016/j.biopha.2022.114097 (2023).
Sarkaki, A. et al. The renoprotective effects of hesperidin on kidney injury induced by exposure to severe chronic dust storm particulate matter through inhibiting the Smads/TGF-beta1 signaling in rat. Naunyn Schmiedebergs Arch. Pharmacol. 396(12), 3615–3626. https://doi.org/10.1007/s00210-023-02562-x (2023).
Amini, N. et al. The renoprotective effects of naringin and trimetazidine on renal ischemia/reperfusion injury in rats through inhibition of apoptosis and downregulation of micoRNA-10a. Biomed. Pharmacother 112, 108568. https://doi.org/10.1016/j.biopha.2019.01.029 (2019).
Yang, L., Besschetnova, T. Y., Brooks, C. R., Shah, J. V. & Bonventre, J. V. Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury. Nat. Med. 16(5), 535–543. https://doi.org/10.1038/nm.2144 (2010).
Saitoh, M. Epithelial-mesenchymal transition is regulated at post-transcriptional levels by transforming growth factor-β signaling during tumor progression. Cancer Sci. 106(5), 481–488. https://doi.org/10.1111/cas.12630 (2015).
Samarakoon, R. et al. Induction of renal fibrotic genes by TGF-β1 requires EGFR activation, p53 and reactive oxygen species. Cell Signal 25(11), 2198–2209. https://doi.org/10.1016/j.cellsig.2013.07.007 (2013).
Huang, R., Fu, P. & Ma, L. Kidney fibrosis: From mechanisms to therapeutic medicines. Signal Transd. Target. Ther. 8(1), 129. https://doi.org/10.1038/s41392-023-01379-7 (2023).
Freudlsperger, C. et al. TGF-β and NF-κB signal pathway cross-talk is mediated through TAK1 and SMAD7 in a subset of head and neck cancers. Oncogene 32(12), 1549–1559. https://doi.org/10.1038/onc.2012.171 (2013).
Alaaeldin, R., Eisa, Y. A., El-Rehany, M. A. & Fathy, M. Vincamine alleviates intrahepatic cholestasis in rats through modulation of NF-kB/PDGF/klf6/PPARgamma and PI3K/Akt pathways. Naunyn Schmiedebergs Arch. Pharmacol. https://doi.org/10.1007/s00210-024-03119-2 (2024).
Vaskivuo, T. E., Stenbäck, F. & Tapanainen, J. S. Apoptosis and apoptosis-related factors Bcl-2, Bax, tumor necrosis factor-alpha, and NF-kappaB in human endometrial hyperplasia and carcinoma. Cancer 95(7), 1463–1471. https://doi.org/10.1002/cncr.10876 (2002).
Vince, J. E. et al. The mitochondrial apoptotic effectors BAX/BAK activate caspase-3 and -7 to trigger NLRP3 inflammasome and caspase-8 driven IL-1β activation. Cell Rep. 25(9), 2339–2353. https://doi.org/10.1016/j.celrep.2018.10.103 (2018).
Bedirli, N. et al. Sevoflurane exerts brain-protective effects against sepsis-associated encephalopathy and memory impairment through caspase 3/9 and Bax/Bcl signaling pathway in a rat model of sepsis. J. Int. Med. Res. 46(7), 2828–2842. https://doi.org/10.1177/0300060518773265 (2018).
Lin, Z., Jin, J. & Shan, X. Fish oils protects against cecal ligation and puncture-induced septic acute kidney injury via the regulation of inflammation, oxidative stress and apoptosis. Int. J. Mol. Med. 44(5), 1771–1780. https://doi.org/10.3892/ijmm.2019.4337 (2019).
Akhurst, R. J. Targeting TGF-β signaling for therapeutic gain. Cold Spring Harb. Perspect. Biol. 9(10), 1. https://doi.org/10.1101/cshperspect.a022301 (2017).
Pekgöz, S. et al. Nebivolol alleviates liver damage caused by methotrexate via AKT1/Hif1α/eNOS signaling. Drug Chem. Toxicol. 45(5), 2153–2159. https://doi.org/10.1080/01480545.2021.1908759 (2022).
Colak, S. et al. Protective effects of nebivolol on ovarian ischemia-reperfusion injury in rat. J. Obstet Gynaecol. Res. 46(11), 2407–2416. https://doi.org/10.1111/jog.14503 (2020).
Gul, R. et al. Comparison of the protective effects of nebivolol and metoprolol against LPS-induced injury in H9c2 cardiomyoblasts. Curr. Issues Mol. Biol. 45(11), 9316–9327. https://doi.org/10.3390/cimb45110583 (2023).
Gandhi, C., Zalawadia, R. & Balaraman, R. Nebivolol reduces experimentally induced warm renal ischemia reperfusion injury in rats. Renal Fail. 30(9), 921–930. https://doi.org/10.1080/08860220802353900 (2008).
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