Oral and systemic diseases under the framework of homeostatic medicine

Jian Zhou , Xiaoyu Li , Lei Hu , Songlin Wang

Dental Research ›› 2026, Vol. 1 ›› Issue (2) : 100027

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Dental Research ›› 2026, Vol. 1 ›› Issue (2) :100027 DOI: 10.1016/j.dtrs.2026.100027
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Oral and systemic diseases under the framework of homeostatic medicine
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Abstract

Homeostatic Medicine is an emerging integrative discipline that focuses on decoding the pivotal role of homeostasis in health and diseases and exploring strategies to restore inherent homeostasis for disease treatment and prevention. It not only provides a transformative theoretical framework, but also novel therapeutic strategies that may potentially revolutionize medical research and clinical practice. In this review, we first introduce the development, fundamental concepts, and core principles of Homeostatic Medicine. Then, we delve into two key regulatory systems as examples of homeostatic control: the nitrate-nitrite-nitric oxide (NO) pathway, mediated by the transporter Sialin, and the multifaceted regulation of oral stem cell (OSC) homeostasis, which encompasses metabolic flexibility, epigenetic programming, signaling networks, and immune-stem cell crosstalk. Under the framework of Homeostatic Medicine, we investigate the mechanisms of homeostatic dysregulation across a spectrum of diseases, including oral diseases, cancer, and cardiovascular and metabolic disorders. Subsequently, we leverage these insights to propose novel therapeutic strategies. Lastly, by synthesizing current knowledge, we outline the future research directions and translational pathways, emphasizing the importance of deep interdisciplinary collaboration in the development of Homeostatic Medicine.

Keywords

Homeostasis / Homeostatic medicine / Oral stem cell / Nitrate / Sialin

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Jian Zhou, Xiaoyu Li, Lei Hu, Songlin Wang. Oral and systemic diseases under the framework of homeostatic medicine. Dental Research, 2026, 1 (2) : 100027 DOI:10.1016/j.dtrs.2026.100027

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References

[1]

S.Y. Wang, et al., DPSCs regulate epithelial-T cell interactions in oral submucous fibrosis, Stem Cell Res. & Ther. 15 (1) (2024).

[2]

G.E. Billman, Homeostasis: The Underappreciated and Far Too Often Ignored Central Organizing Principle of Physiology, Front. Physiol. 11 (2020) 2020.

[3]

C. Lopez-Otin, G. Kroemer, Hallmarks of Health, Cell 184 (1) (2021) 33-63.

[4]

L.Z. Qin, et al., Homeostatic medicine: new strategy and concept of health maintenance as well as diagnosis and treatment of diseases, Zhonghua Kou Qiang Yi Xue Za Zhi 58 (2) (2023) 109-117.

[5]

D. Furman, et al., Chronic inflammation in the etiology of disease across the life span, Nat. Med. 25 (12) (2019) 1822-1832.

[6]

L. Kraehenbuehl, et al., Enhancing immunotherapy in cancer by targeting emerging immunomodulatory pathways, Nat. Rev. Clin. Oncol. 19 (1) (2022) 37-50.

[7]

S. Wang, L. Qin, Homeostatic medicine: a strategy for exploring health and disease, Curr. Med. 1 (1) (2022) 16.

[8]

Unschuld, P.U., H. Tessenow, and J. Zheng, Huang Di Nei Jing Su Wen: An Annotated Translation of Huang Di’s Inner Classic - Basic Questions: 2 Volumes. 2011: University of California Press.

[9]

E.F. Adolph, Early concepts of physiological regulations, Physiol. Rev. 41 (1961) 737-770.

[10]

L.H. Toledo-Pereyra, Introduction à L′Etude de la Médecine Expérimentale. Surgical revolution. Part I, J. Invest Surg. 22 (3) (2009) 157-161.

[11]

S.J. Cooper, From Claude Bernard to Walter Cannon. Emergence of the concept of homeostasis, Appetite 51 (3) (2008) 419-427.

[12]

C.F. Arias, et al., A functional approach to homeostatic regulation, Biol. Direct 19 (1) (2024) 134.

[13]

S. Chirumbolo, A. Vella, Molecules, Information and the Origin of Life: What Is Next? Molecules 26 (4) (2021).

[14]

J.D. Humphrey, M.A. Schwartz, Vascular Mechanobiology: Homeostasis, Adaptation, and Disease, Annu Rev. Biomed. Eng. 23 (2021) 1-27.

[15]

G.B. Kamm, et al., A synaptic temperature sensor for body cooling, Neuron 109 (20) (2021) 3283-3297.e11.

[16]

R.H. Carpenter, Homeostasis: a plea for a unified approach, Adv. Physiol. Educ. 28 (1-4) (2004) 180-187.

[17]

L. Qin, S. Wang, Protective roles of inorganic nitrate in health and diseases, Curr. Med. 1 (1) (2022).

[18]

S.L. Wang, Development and application of homeostatic medicine in stomatology, Zhonghua Kou Qiang Yi Xue Za Zhi 59 (2) (2024) 119-123.

[19]

H. Atamna, et al., Organ reserve, excess metabolic capacity, and aging, Biogerontology 19 (2) (2018) 171-184.

[20]

Y. Tang, et al., Modulation of the dynamics of cerebellar Purkinje cells through the interaction of excitatory and inhibitory feedforward pathways, PLoS Comput. Biol. 17 (2) (2021) e1008670.

[21]

L. Campana, et al., Liver regeneration and inflammation: from fundamental science to clinical applications, Nat. Rev. Mol. Cell Biol. 22 (9) (2021) 608-624.

[22]

R. Palsson, S.S. Waikar, Renal Functional Reserve Revisited, Adv. Chronic Kidney Dis. 25 (3) (2018) e1-e8.

[23]

M. D'Acierno, R.A. Fenton, E.J. Hoorn, The biology of water homeostasis, Nephrol. Dial. Transpl. 40 (4) (2025) 632-640.

[24]

L. Meoli, D. Günzel, The role of claudins in homeostasis, Nat. Rev. Nephrol. 19 (9) (2023) 587-603.

[25]

L.L. Hamm, N. Nakhoul, K.S. Hering-Smith, Acid-Base Homeostasis, Clin. J. Am. Soc. Nephrol. 10 (12) (2015) 2232-2242.

[26]

J. Danziger, M.L. Zeidel, Osmotic homeostasis, Clin. J. Am. Soc. Nephrol. 10 (5) (2015) 852-862.

[27]

C.R. Harapas, et al., Organellar homeostasis and innate immune sensing, Nat. Rev. Immunol. 22 (9) (2022) 535-549.

[28]

D. Acosta-Alvear, et al., Homeostasis control in health and disease by the unfolded protein response, Nat. Rev. Mol. Cell Biol. 26 (3) (2025) 193-212.

[29]

J.J. Collier, et al., Mitochondrial signalling and homeostasis: from cell biology to neurological disease, Trends Neurosci. 46 (2) (2023) 137-152.

[30]

S. Herzig, R.J. Shaw, AMPK: guardian of metabolism and mitochondrial homeostasis, Nat. Rev. Mol. Cell Biol. 19 (2) (2018) 121-135.

[31]

X. Hu, F. Guo, Amino Acid Sensing in Metabolic Homeostasis and Health, Endocr. Rev. 42 (1) (2021) 56-76.

[32]

T. TeSlaa, et al., The pentose phosphate pathway in health and disease, Nat. Metab. 5 (8) (2023) 1275-1289.

[33]

G.R. Steinberg, D.G. Hardie, New insights into activation and function of the AMPK, Nat. Rev. Mol. Cell Biol. 24 (4) (2023) 255-272.

[34]

H. Yoon, et al., Lipid metabolism in sickness and in health: Emerging regulators of lipotoxicity, Mol. Cell 81 (18) (2021) 3708-3730.

[35]

B. Thorens, Neuronal glucose sensing mechanisms and circuits in the control of insulin and glucagon secretion, Physiol. Rev. 104 (4) (2024) 1461-1486.

[36]

M.G. Myers Jr. et al., Central nervous system regulation of organismal energy and glucose homeostasis, Nat. Metab. 3 (6) (2021) 737-750.

[37]

P.V. Röder, et al., Pancreatic regulation of glucose homeostasis, Exp. Mol. Med 48 (3) (2016) e219.

[38]

A.R. Saltiel, Insulin signaling in health and disease, J. Clin. Invest 131 (1) (2021).

[39]

M.N. Cramer, et al., Human temperature regulation under heat stress in health, disease, and injury, Physiol. Rev. 102 (4) (2022) 1907-1989.

[40]

J.D. Périard, T.M.H. Eijsvogels, H.A.M. Daanen, Exercise under heat stress: thermoregulation, hydration, performance implications, and mitigation strategies, Physiol. Rev. 101 (4) (2021) 1873-1979.

[41]

J.Y. Lee, R.M. Tsolis, A.J. Bäumler, The microbiome and gut homeostasis, Science 377 (6601) (2022) eabp9960.

[42]

R.J. Lamont, H. Koo, G. Hajishengallis, The oral microbiota: dynamic communities and host interactions, Nat. Rev. Microbiol 16 (12) (2018) 745-759.

[43]

H. Sies, R.J. Mailloux, U. Jakob, Fundamentals of redox regulation in biology, Nat. Rev. Mol. Cell Biol. 25 (9) (2024) 701-719.

[44]

R. Baron, M. Kneissel, WNT signaling in bone homeostasis and disease: from human mutations to treatments, Nat. Med 19 (2) (2013) 179-192.

[45]

L. Kong, et al., Macrophages in Bone Homeostasis, Curr. Stem Cell Res Ther. 14 (6) (2019) 474-481.

[46]

J.M. Kim, et al., Osteoblast-Osteoclast Communication and Bone Homeostasis, Cells 9 (9) (2020).

[47]

G. Yuan, et al., Skeletal stem cells in bone development, homeostasis, and disease, Protein Cell 15 (8) (2024) 559-574.

[48]

S. Berry, L. Pelkmans, Mechanisms of cellular mRNA transcript homeostasis, Trends Cell Biol. 32 (8) (2022) 655-668.

[49]

J. Zhou, et al., Nitrate and body homeostasis, Medicine 1 (1) (2024).

[50]

H. Liu, et al., From nitrate to NO: potential effects of nitrate-reducing bacteria on systemic health and disease, Eur. J. Med. Res. 28 (1) (2023) 425.

[51]

O. Mazuryk, et al., Nitric Oxide Signaling and Sensing in Age-Related Diseases, Antioxid. (Basel) 13 (10) (2024).

[52]

J.O. Lundberg, et al., Roles of dietary inorganic nitrate in cardiovascular health and disease, Cardiovasc Res 89 (3) (2011) 525-532.

[53]

E. Weitzberg, J.O. Lundberg, Novel aspects of dietary nitrate and human health, Annu Rev. Nutr. 33 (2013) 129-159.

[54]

T.M. Knight, et al., Estimation of dietary intake of nitrate and nitrite in Great Britain, Food Chem. Toxicol. 25 (4) (1987) 277-285.

[55]

B. Spiegelhalder, G. Eisenbrand, R. Preussmann, Influence of dietary nitrate on nitrite content of human saliva: possible relevance to in vivo formation of N-nitroso compounds, Food Cosmet. Toxicol. 14 (6) (1976) 545-548.

[56]

M. Silva-Cunha, R. Lacchini, J.E. Tanus-Santos, Facilitating Nitrite-Derived S-Nitrosothiol Formation in the Upper Gastrointestinal Tract in the Therapy of Cardiovascular Diseases, Antioxid. (Basel) 13 (6) (2024).

[57]

R.M. Pluta, et al., Nitrite infusions to prevent delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage, Jama 293 (12) (2005) 1477-1484.

[58]

J.P. Kinsella, et al., Early inhaled nitric oxide therapy in premature newborns with respiratory failure, N. Engl. J. Med 355 (4) (2006) 354-364.

[59]

J.O. Lundberg, E. Weitzberg, M.T. Gladwin, The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics, Nat. Rev. Drug Discov. 7 (2) (2008) 156-167.

[60]

L. Jin, et al., Active secretion and protective effect of salivary nitrate against stress in human volunteers and rats, Free Radic. Biol. Med 57 (2013) 61-67.

[61]

S.M. Nadtochiy, L.S. Burwell, P.S. Brookes, Cardioprotection and mitochondrial S-nitrosation: effects of S-nitroso-2-mercaptopropionyl glycine (SNO-MPG) in cardiac ischemia-reperfusion injury, J. Mol. Cell Cardiol. 42 (4) (2007) 812-825.

[62]

M.D. Ferrer, et al., Nitrite Attenuates the In Vitro Inflammatory Response of Immune Cells to the SARS-CoV-2 S Protein without Interfering in the Antioxidant Enzyme Activation, Int J. Mol. Sci. 25 (5) (2024).

[63]

L. Qin, et al., Sialin (SLC17A5) functions as a nitrate transporter in the plasma membrane, Proc. Natl. Acad. Sci. USA 109 (33) (2012) 13434-13439.

[64]

A.M. Jones, et al., Dietary Nitrate and Nitric Oxide Metabolism: Mouth, Circulation, Skeletal Muscle, and Exercise Performance, Med Sci. Sports Exerc 53 (2) (2021) 280-294.

[65]

L. Ma, et al., Nitrate and Nitrite in Health and Disease, Aging Dis. 9 (5) (2018) 938-945.

[66]

J.F. Harb, et al., Base editing corrects the common Salla disease SLC17A5c.115C > T variant, Mol. Ther. Nucleic Acids 34 (2023) 102022.

[67]

X. Feng, et al., Dietary nitrate supplementation prevents radiotherapy-induced xerostomia, Elife 10 (2021).

[68]

S. Li, et al., Inorganic nitrate alleviates irradiation-induced salivary gland damage by inhibiting pyroptosis, Free Radic. Biol. Med 175 (2021) 130-140.

[69]

H. Jiang, et al., Dietary nitrite improves insulin signaling through GLUT4 translocation, Free Radic. Biol. Med 67 (2014) 51-57.

[70]

A. Gola, E. Fuchs, Environmental control of lineage plasticity and stem cell memory, Curr. Opin. Cell Biol. 69 (2021) 88-95.

[71]

D. Babaki, M.M. Matin, Odontoblast-like Cytodifferentiation of Dental Stem Cells: A Review, Iran. Endod. J. 15 (2) (2020) 79-89.

[72]

Y. Yu, et al., Function of Orofacial Stem Cells in Tooth Eruption: An Evolving Perspective, Chin. J. Dent. Res. 24 (3) (2021) 143-152.

[73]

M. Cabaña-Muñoz, et al., Adult Mesenchymal Stem Cells from Oral Cavity and Surrounding Areas: Types and Biomedical Applications, Pharmaceutics 15 (8) (2023).

[74]

Z. Mai, et al., Translational and Clinical Applications of Dental Stem Cell-Derived Exosomes, Front. Genet. 12 (2021).

[75]

S. Trubin, D.B. Patel, A. Tian, Regulation of the Intestinal Stem Cell Pool and Proliferation in Drosophila, Cells 13 (22) (2024).

[76]

L. Hu, Y. Liu, S. Wang, Stem cell-based tooth and periodontal regeneration, Oral. Dis. 24 (5) (2017) 696-705.

[77]

L. Shang, J. Shao, S. Ge, Immunomodulatory functions of oral mesenchymal stem cells: Novel force for tissue regeneration and disease therapy, J. Leukoc. Biol. 110 (3) (2021) 539-552.

[78]

X. Zhang, et al., Oral stem cells, decoding and mapping the resident cells populations, Biomater. Transl. 3 (1) (2022) 24-30.

[79]

I. Okic-Dordevic, et al., Dental mesenchymal stromal/stem cells in different microenvironments- implications in regenerative therapy, World J. Stem Cells 13 (12) (2021) 1863-1880.

[80]

S. Shi, S. Gronthos, Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp, J. Bone Min. Res 18 (4) (2003) 696-704.

[81]

E.R. Moore, et al., CGRP and Shh Mediate the Dental Pulp Cell Response to Neuron Stimulation, J. Dent. Res 101 (9) (2022) 1119-1126.

[82]

A. Li, et al., Role of Heparan Sulfate in Vasculogenesis of Dental Pulp Stem Cells, J. Dent. Res 102 (2) (2023) 207-216.

[83]

R. Pires, et al., Electrical Stimulation of Oral Tissue-Derived Stem Cells: Unlocking New Potential for Dental and Periodontal Regeneration, Cells 14 (11) (2025).

[84]

F. Wei, et al., Mechanical Force-Induced Specific MicroRNA Expression in Human Periodontal Ligament Stem Cells, Cells Tissues Organs 199 (5-6) (2014) 353-363.

[85]

L. Xiaoyu, J. Ou, W. Songlin, Molecular mechanisms of cellular metabolic homeostasis in stem cells, Int. J. Oral. Sci. 15 (4) (2023) 527-539.

[86]

Y. Su, et al., Physiologic Levels of Endogenous Hydrogen Sulfide Maintain the Proliferation and Differentiation Capacity of Periodontal Ligament Stem Cells, J. Periodontol. 86 (11) (2015) 1276-1286.

[87]

Y. Li, et al., Epigenetic control of dental stem cells: progress and prospects in multidirectional differentiation, Epigenetics & Chromatin 17 (1) (2024).

[88]

K. Nasiri, et al., MicroRNAs Function in Dental Stem Cells as a Promising Biomarker and Therapeutic Target for Dental Diseases, Mol. Diagn. & Ther. 27 (6) (2023) 703-722.

[89]

A. Hussain, H. Tebyaniyan, D. Khayatan, The Role of Epigenetic in Dental and Oral Regenerative Medicine by Different Types of Dental Stem Cells: A Comprehensive Overview, Stem Cells Int. 2022 (2022).

[90]

X. Li, O. Jiang, S. Wang, Molecular mechanisms of cellular metabolic homeostasis in stem cells, Int. J. Oral. Sci. 15 (1) (2023).

[91]

V.O.C. Rigaud, et al., Stem Cell Metabolism: Powering Cell-Based Therapeutics, Cells 9 (11) (2020).

[92]

V. Scandella, et al., Neural stem cell metabolism revisited: a critical role for mitochondria, Trends Endocrinol. Metab. 34 (8) (2023) 446-461.

[93]

R.P. Chakrabarty, N.S. Chandel, Mitochondria as Signaling Organelles Control Mammalian Stem Cell Fate, Cell Stem Cell 28 (3) (2021) 394-408.

[94]

K. Pieknell, et al., LIN28A enhances regenerative capacity of human somatic tissue stem cells via metabolic and mitochondrial reprogramming, Cell Death Differ. 29 (3) (2022) 540-555.

[95]

H.T. Langer, et al., AMPK as a mediator of tissue preservation: time for a shift in dogma? Nat. Rev. Endocrinol. 20 (9) (2024) 526-540.

[96]

I. Calatayud-Baselga, et al., Autophagy drives the conversion of developmental neural stem cells to the adult quiescent state, Nat. Commun. 14 (1) (2023) 7541.

[97]

N. Yin, et al., SZT2 maintains hematopoietic stem cell homeostasis via nutrient-mediated mTORC1 regulation, J. Clin. Invest 132 (20) (2022).

[98]

M. Jhanwar-Uniyal, et al., Discrete Mechanistic Target of Rapamycin Signaling Pathways, Stem Cells, and Therapeutic Targets, Cells 13 (5) (2024).

[99]

L. Cao, et al., Glycolytic Pfkp acts as a Lin41 protein kinase to promote endodermal differentiation of embryonic stem cells, EMBO Rep. 24 (3) (2023) e55683.

[100]

A.T. Vessoni, A.R. Muotri, O.K. Okamoto, Autophagy in stem cell maintenance and differentiation, Stem Cells Dev. 21 (4) (2012) 513-520.

[101]

X. Xu, et al., Autophagy, a double-edged sword for oral tissue regeneration, J. Adv. Res 59 (2024) 141-159.

[102]

X. Xu, et al., Melatonin Increased Autophagy Level to Facilitate Osteogenesis of Inflamed PDLSCs Through TMEM110 Signaling Pathways, J. Pineal Res 77 (2) (2025) e70039.

[103]

C. Zhang, Y. Meng, J. Han, Emerging roles of mitochondrial functions and epigenetic changes in the modulation of stem cell fate, Cell Mol. Life Sci. 81 (1) (2024) 26.

[104]

B. Wang, et al., Lipid metabolism within the bone micro-environment is closely associated with bone metabolism in physiological and pathophysiological stages, Lipids Health Dis. 21 (1) (2022) 5.

[105]

E. Villa, et al., mTORC1 stimulates cell growth through SAM synthesis and m(6)A mRNA-dependent control of protein synthesis, Mol. Cell 81 (10) (2021) 2076-2093.e9.

[106]

D. Pladevall-Morera, J.J. Zylicz, Chromatin as a sensor of metabolic changes during early development, Front Cell Dev. Biol. 10 (2022) 1014498.

[107]

M. Hu, Z. Fan, Role and mechanisms of histone methylation in osteogenic/odontogenic differentiation of dental mesenchymal stem cells, Int J. Oral. Sci. 17 (1) (2025) 24.

[108]

J. Xu, et al., KDM6B epigenetically regulates odontogenic differentiation of dental mesenchymal stem cells, Int J. Oral. Sci. 5 (4) (2013) 200-205.

[109]

D. Liu, et al., Demethylation of IGFBP5 by Histone Demethylase KDM6B Promotes Mesenchymal Stem Cell-Mediated Periodontal Tissue Regeneration by Enhancing Osteogenic Differentiation and Anti-Inflammation Potentials, Stem Cells 33 (8) (2015) 2523-2536.

[110]

G. Yu, et al., Demethylation of SFRP2 by histone demethylase KDM2A regulated osteo-/dentinogenic differentiation of stem cells of the apical papilla, Cell Prolif. 49 (3) (2016) 330-340.

[111]

R. Gao, et al., Depletion of histone demethylase KDM2A inhibited cell proliferation of stem cells from apical papilla by de-repression of p15INK4B and p27Kip1, Mol. Cell. Biochem. 379 (1-2) (2013) 115-122.

[112]

R. Dong, et al., Depletion of histone demethylase KDM2A enhanced the adipogenic and chondrogenic differentiation potentials of stem cells from apical papilla, Exp. Cell Res. 319 (18) (2013) 2874-2882.

[113]

N.C. Huynh, et al., Inhibition of Histone Deacetylases Enhances the Osteogenic Differentiation of Human Periodontal Ligament Cells, J. Cell Biochem 117 (6) (2016) 1384-1395.

[114]

F. Paino, et al., Histone deacetylase inhibition with valproic acid downregulates osteocalcin gene expression in human dental pulp stem cells and osteoblasts: evidence for HDAC2 involvement, Stem Cells 32 (1) (2014) 279-289.

[115]

Z. Fan, et al., BCOR regulates mesenchymal stem cell function by epigenetic mechanisms, Nat. Cell Biol. 11 (8) (2009) 1002-1009.

[116]

X. Zhu, et al., Novel BCOR mutation in a boy with Lenz microphthalmia/oculo-facio-cardio-dental (OFCD) syndrome, Gene 571 (1) (2015) 142-144.

[117]

Uddin, M.G. and T.E. Fandy, DNA methylation inhibitors: Retrospective and perspective view. Adv. Cancer Res 152 (2021) 205-223.

[118]

J. Shi, et al., The concurrence of DNA methylation and demethylation is associated with transcription regulation, Nat. Commun. 12 (1) (2021) 5285.

[119]

E. Giabicani, et al., Dental pulp stem cells as a promising model to study imprinting diseases, Int J. Oral. Sci. 14 (1) (2022) 19.

[120]

R.I.F. Assis, et al., Osteogenic Commitment of Human Periodontal Ligament Cells Is Predetermined by Methylation, Chromatin Accessibility and Expression of Key Transcription Factors, Cells 11 (7) (2022).

[121]

Z. Liu, et al., DNA Demethylation Rescues the Impaired Osteogenic Differentiation Ability of Human Periodontal Ligament Stem Cells in High Glucose, Sci. Rep. 6 (2016) 27447.

[122]

T. Ai, et al., DNA methylation profile is associated with the osteogenic potential of three distinct human odontogenic stem cells, Signal Transduct. Target Ther. 3 (2018) 1.

[123]

X. Gu, et al., Profiling and functional characterization of long noncoding RNAs during human tooth development, Int. J. Oral. Sci. 17 (1) (2025).

[124]

A.B. Herman, D. Tsitsipatis, M. Gorospe, Integrated lncRNA function upon genomic and epigenomic regulation, Mol. Cell 82 (12) (2022) 2252-2266.

[125]

W.C. Liang, et al., H19 activates Wnt signaling and promotes osteoblast differentiation by functioning as a competing endogenous RNA, Sci. Rep. 6 (2016) 20121.

[126]

S. Ghafouri-Fard, et al., The impact of non-coding RNAs on normal stem cells, Biomed. Pharm. 142 (2021) 112050.

[127]

Z. Li, X. Guo, S. Wu, Epigenetic silencing of KLF2 by long non-coding RNA SNHG1 inhibits periodontal ligament stem cell osteogenesis differentiation, Stem Cell Res Ther. 11 (1) (2020) 435.

[128]

H. Liu, et al., LncRNA, PLXDC2-OT Promoted the Osteogenesis Potentials of MSCs by Inhibiting the Deacetylation Function of RBM6/SIRT7 Complex and OSX Specific Isoform, Stem Cells 39 (8) (2021) 1049-1066.

[129]

S.N. Hurwitz, S.K. Jung, P. Kurre, Hematopoietic stem and progenitor cell signaling in the niche, Leukemia 34 (12) (2020) 3136-3148.

[130]

M. Maccaferri, et al., Human dental pulp stem cells modulate pro-inflammatory macrophages both through cell-to-cell contact and paracrine signaling, Front Immunol. 15 (2024) 1440974.

[131]

X.P. Wang, et al., An integrated gene regulatory network controls stem cell proliferation in teeth, PLoS Biol. 5 (6) (2007) e159.

[132]

G. Yang, et al., Mesenchymal TGF-βSignaling Orchestrates Dental Epithelial Stem Cell Homeostasis Through Wnt Signaling, Stem Cells 32 (11) (2014) 2939-2948.

[133]

J. Li, et al., BMP-SHH Signaling Network Controls Epithelial Stem Cell Fate via Regulation of Its Niche in the Developing Tooth, Dev. Cell 33 (2) (2015) 125-135.

[134]

D. Cheng, et al., Canonical Wnt Pathway Enhanced Dental Pulp Mesenchymal Stem Cells-Mediated Cementum Regeneration, J. Oral. Rehabil. (2025).

[135]

J.H. Driskill, D. Pan, Control of stem cell renewal and fate by YAP and TAZ, Nat. Rev. Mol. Cell Biol. 24 (12) (2023) 895-911.

[136]

M.P. Dieterle, et al., Role of mechanotransduction in periodontal homeostasis and disease, J. Dent. Res 100 (11) (2021) 1210-1219.

[137]

J. Wang, et al., LRP6/filamentous-actin signaling facilitates osteogenic commitment in mechanically induced periodontal ligament stem cells, Cell Mol. Biol. Lett. 28 (1) (2023) 7.

[138]

C.R. Harrell, V. Djonov, V. Volarevic, The Cross-Talk between Mesenchymal Stem Cells and Immune Cells in Tissue Repair and Regeneration, Int J. Mol. Sci. 22 (5) (2021).

[139]

E.Z. Poirier, How stem cells respond to infection, inflammation and ageing, Nat. Rev. Immunol. (2025).

[140]

G. Ding, et al., Suppression of T Cell Proliferation by Root Apical Papilla Stem Cells in vitro, Cells Tissues Organs 191 (5) (2010) 357-364.

[141]

M. Di Nicola, et al., Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli, Blood 99 (10) (2002) 3838-3843.

[142]

N. Wada, et al., Immunomodulatory properties of human periodontal ligament stem cells, J. Cell Physiol. 219 (3) (2009) 667-676.

[143]

K. Sato, et al., Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells, Blood 109 (1) (2007) 228-234.

[144]

O. Liu, et al., Periodontal ligament stem cells regulate B lymphocyte function via programmed cell death protein 1, Stem Cells 31 (7) (2013) 1371-1382.

[145]

K. English, et al., Cell contact, prostaglandin E(2) and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of CD4+CD25(High) forkhead box P3+ regulatory T cells, Clin. Exp. Immunol. 156 (1) (2009) 149-160.

[146]

J. Kim, P. Hematti, Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages, Exp. Hematol. 37 (12) (2009) 1445-1453.

[147]

F. Yan, et al., Human dental pulp stem cells regulate allogeneic NK cells’ function via induction of anti-inflammatory purinergic signalling in activated NK cells, Cell Prolif. 52 (3) (2019).

[148]

Z. Yang, et al., Dental pulp stem cells accelerate wound healing through CCL2-induced M2 macrophages polarization, iScience 26 (10) (2023).

[149]

J. Liu, et al., Periodontal ligament stem cells promote polarization of M2 macrophages, J. Leukoc. Biol. 111 (6) (2022) 1185-1197.

[150]

Z. Ma, et al., Function of Innate Lymphoid Cells in Periodontal Tissue Homeostasis: A Narrative Review, Int. J. Mol. Sci. 24 (7) (2023).

[151]

Q. Zhao, et al., A Salivary Gland Resident Macrophage Subset Regulating Radiation Responses, J. Dent. Res 102 (5) (2023) 536-545.

[152]

D. Liu, et al., Mesenchymal stem cells derived from inflamed periodontal ligaments exhibit impaired immunomodulation, J. Clin. Periodontol. 39 (12) (2012) 1174-1182.

[153]

Y. Liu, et al., Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-γ and TNF-α, Nat. Med 17 (12) (2011) 1594-1601.

[154]

Y. Liu, R. Yang, S. Shi, Systemic infusion of mesenchymal stem cells improves cell-based bone regeneration via upregulation of regulatory T cells, Tissue Eng. Part A 21 (3-4) (2015) 498-509.

[155]

S. Yu, et al., Inflammatory microenvironment of moderate pulpitis enhances the osteo-/odontogenic potential of dental pulp stem cells by autophagy, Int Endod. J. 57 (10) (2024) 1465-1477.

[156]

Y. Lin, et al., Inhibition of Streptococcus mutans biofilm formation by strategies targeting the metabolism of exopolysaccharides, Crit. Rev. Microbiol 47 (5) (2021) 667-677.

[157]

M. Tatullo, et al., Dental pulp stem cells: function, isolation and applications in regenerative medicine, J. Tissue Eng. Regen. Med 9 (11) (2015) 1205-1216.

[158]

M. Gallorini, et al., Relevance of Cellular Redox Homeostasis for Vital Functions of Human Dental Pulp Cells, Antioxid. (Basel) 11 (1) (2021).

[159]

C.L. Hahn, F.R. Liewehr, Update on the adaptive immune responses of the dental pulp, J. Endod. 33 (7) (2007) 773-781.

[160]

S. Pohl, et al., Understanding dental pulp inflammation: from signaling to structure, Front Immunol. 15 (2024) 1474466.

[161]

M. Kilian, et al., The oral microbiome - an update for oral healthcare professionals, Br. Dent. J. 221 (10) (2016) 657-666.

[162]

G. Hajishengallis, R.J. Lamont, Beyond the red complex and into more complexity: the polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology, Mol. Oral. Microbiol 27 (6) (2012) 409-419.

[163]

L. Lin, et al., UCHL1 Impairs Periodontal Ligament Stem Cell Osteogenesis in Periodontitis, J. Dent. Res 102 (1) (2023) 61-71.

[164]

M. Xu, et al., SLC30A4-AS1 Mediates the Senescence of Periodontal Ligament Stem Cells in Inflammatory Environments via the Alternative Splicing of TP53BP1, Cell Prolif. 58 (4) (2025) e13778.

[165]

X. Li, et al., Mesenchymal stem cell-derived apoptotic bodies alleviate alveolar bone destruction by regulating osteoclast differentiation and function, Int J. Oral. Sci. 15 (1) (2023) 51.

[166]

Q. Niu, et al., FoxO1-Overexpressed Small Extracellular Vesicles Derived from hPDLSCs Promote Periodontal Tissue Regeneration by Reducing Mitochondrial Dysfunction to Regulate Osteogenesis and Inflammation, Int J. Nanomed. 19 (2024) 8751-8768.

[167]

Y.Y. Zhang, et al., Fumarate Restrains Alveolar Bone Restoration via Regulating H3K9 Methylation, J. Dent. Res 103 (12) (2024) 1302-1312.

[168]

L. Li, et al., Oxidative Stress-Induced Hypermethylation of KLF5 Promoter Mediated by DNMT3B Impairs Osteogenesis by Diminishing the Interaction with beta-Catenin, Antioxid. Redox Signal 35 (1) (2021) 1-20.

[169]

S. Nusrat, et al., Epigenetic Dysregulation and Osteocyte Senescence: Convergent Drivers of Osteosarcopenia in Aging Bone and Muscle, Aging Dis. (2025).

[170]

X. Zhao, et al., Circular RNA BIRC6 depletion promotes osteogenic differentiation of periodontal ligament stem cells via the miR-543/PTEN/PI3K/AKT/mTOR signaling pathway in the inflammatory microenvironment, Stem Cell Res Ther. 13 (1) (2022) 417.

[171]

Z. Zhang, et al., Periodontal ligament stem cells in the periodontitis niche: inseparable interactions and mechanisms, J. Leukoc. Biol. 110 (3) (2021) 565-576.

[172]

R.J. Bertelsen, et al., Association of oral bacteria with oral hygiene habits and self-reported gingival bleeding, J. Clin. Periodo 49 (8) (2022) 768-781.

[173]

V. Kapil, et al., The Noncanonical Pathway for In Vivo Nitric Oxide Generation: The Nitrate-Nitrite-Nitric Oxide Pathway, Pharm. Rev. 72 (3) (2020) 692-766.

[174]

D.P. Wicaksono, et al., Nitrite Production from Nitrate and Its Link with Lactate Metabolism in Oral Veillonella spp, Appl. Environ. Microbiol 86 (20) (2020).

[175]

L.M. Estes Bright, et al., Dual Action Nitric Oxide and Fluoride Ion-Releasing Hydrogels for Combating Dental Caries, ACS Appl. Mater. Interfaces 14 (19) (2022) 21916-21930.

[176]

B.T. Rosier, et al., The Importance of Nitrate Reduction for Oral Health, J. Dent. Res 101 (8) (2022) 887-897.

[177]

J.O. Lundberg, E. Weitzberg, Nitric oxide signaling in health and disease, Cell 185 (16) (2022) 2853-2878.

[178]

D. Mazurel, et al., Nitrate and a nitrate-reducing Rothia aeria strain as potential prebiotic or synbiotic treatments for periodontitis, NPJ Biofilms Micro 9 (1) (2023) 40.

[179]

Y. Jockel-Schneider, et al., Nitrate-rich diet alters the composition of the oral microbiota in periodontal recall patients, J. Periodo 92 (11) (2021) 1536-1545.

[180]

Y. Si, et al., Nitrate-driven maintenance of lipid homeostasis by M2 macrophages alleviates atherosclerosis via downregulation of LOX1 expression and reduction of lipid deposition, Sci. China Life Sci. 68 (10) (2025) 2995-3009.

[181]

R. Saini, et al., Neuronal Nitric Oxide Synthase (nNOS) in Neutrophils: An Insight, Rev. Physiol. Biochem Pharm. 180 (2021) 49-83.

[182]

P. Zhan, et al., FoxO1 mediates odontoblast differentiation of hDPSCs via B cell-derived ANGPTL1 in dental caries: A laboratory investigation, Int Endod. J. 58 (5) (2025) 757-775.

[183]

M. Parirokh, M. Torabinejad, Mineral trioxide aggregate: a comprehensive literature review-Part III: Clinical applications, drawbacks, and mechanism of action, J. Endod. 36 (3) (2010) 400-413.

[184]

Y.J. Kim, et al., Mineral trioxide aggregate-induced AMPK activation stimulates odontoblastic differentiation of human dental pulp cells, Int Endod. J. 54 (5) (2021) 753-767.

[185]

Y. Liu, et al., Wnt/beta-catenin plays a dual function in calcium hydroxide induced proliferation, migration, osteogenic differentiation and mineralization in vitro human dental pulp stem cells, Int Endod. J. 56 (1) (2023) 92-102.

[186]

Z. Xie, et al., Antimicrobial Peptide- and Dentin Matrix-Functionalized Hydrogel for Vital Pulp Therapy via Synergistic Bacteriostasis, Immunomodulation, and Dentinogenesis, Adv. Health Mater. 13 (18) (2024) e2303709.

[187]

C.W. Chi, et al., Multiple growth factors accommodated degradable submicron calcium sulfate hemihydrate/porous hydroxyapatite for dentin-pulp regeneration, Biomater. Adv. 140 (2022) 213045.

[188]

J. Chen, et al., Resolvin E1 accelerates pulp repair by regulating inflammation and stimulating dentin regeneration in dental pulp stem cells, Stem Cell Res Ther. 12 (1) (2021) 75.

[189]

K.M. Galler, et al., EDTA conditioning of dentine promotes adhesion, migration and differentiation of dental pulp stem cells, Int Endod. J. 49 (6) (2016) 581-590.

[190]

Y. Liu, et al., Challenges and Tissue Engineering Strategies of Periodontal-Guided Tissue Regeneration, Tissue Eng. Part C. Methods 28 (8) (2022) 405-419.

[191]

B. Yin, et al., Smart injectable hydrogels for periodontal regeneration: Recent advancements in biomaterials and biofabrication strategies, Mater. Today Bio 32 (2025) 101855.

[192]

X. Wang, et al., Recent Strategies and Advances in Hydrogel-Based Delivery Platforms for Bone Regeneration, Nanomicro Lett. 17 (1) (2024) 73.

[193]

H. Guo, et al., Injectable and Self-Healing Hydrogels with Double-Dynamic Bond Tunable Mechanical, Gel-Sol Transition and Drug Delivery Properties for Promoting Periodontium Regeneration in Periodontitis, ACS Appl. Mater. Interfaces 13 (51) (2021) 61638-61652.

[194]

M.G. Balta, B.G. Loos, E.A. Nicu, Emerging Concepts in the Resolution of Periodontal Inflammation: A Role for Resolvin E1, Front Immunol. (8) (2017) 1682.

[195]

E. Albuquerque-Souza, et al., Maresin-1 and Resolvin E1 Promote Regenerative Properties of Periodontal Ligament Stem Cells Under Inflammatory Conditions, Front Immunol. 11 (2020) 585530.

[196]

C.T. Lee, et al., Resolvin E1 Reverses Experimental Periodontitis and Dysbiosis, J. Immunol. 197 (7) (2016) 2796-2806.

[197]

Y.L. Zhang, et al., Metformin combats high glucose-induced damage to the osteogenic differentiation of human periodontal ligament stem cells via inhibition of the NPR3-mediated MAPK pathway, Stem Cell Res Ther. 13 (1) (2022) 305.

[198]

L. Jia, et al., Metformin promotes osteogenic differentiation and protects against oxidative stress-induced damage in periodontal ligament stem cells via activation of the Akt/Nrf2 signaling pathway, Exp. Cell Res 386 (2) (2020) 111717.

[199]

Z. Yang, et al., Effect of metformin on human periodontal ligament stem cells cultured with polydopamine-templated hydroxyapatite, Eur. J. Oral. Sci. 127 (3) (2019) 210-221.

[200]

M. Ghorbaninejad, et al., Epidrugs: novel epigenetic regulators that open a new window for targeting osteoblast differentiation, Stem Cell Res Ther. 11 (1) (2020) 456.

[201]

J. Hu, et al., Periodontal regeneration in swine after cell injection and cell sheet transplantation of human dental pulp stem cells following good manufacturing practice, Stem Cell Res. & Ther. 7 (1) (2016).

[202]

Y. Cao, et al., Adenovirus-mediated transfer of hepatocyte growth factor gene to human dental pulp stem cells under good manufacturing practice improves their potential for periodontal regeneration in swine, Stem Cell Res. & Ther. 6 (1) (2015).

[203]

Y. Liu, et al., Impact of allogeneic dental pulp stem cell injection on tissue regeneration in periodontitis: a multicenter randomized clinical trial, Signal Transduct. Target Ther. 10 (1) (2025) 239.

[204]

D. Lin, et al., Crosstalk between the oral microbiota, mucosal immunity, and the epithelial barrier regulates oral mucosal disease pathogenesis, Mucosal Immunol. 14 (6) (2021) 1247-1258.

[205]

H.C. Pitot, The molecular biology of carcinogenesis, Cancer 72 (3) (1993) 962-970.

[206]

P. Kordowitzki, A. Grzeczka, Unveiling the Relation between Cellular Ageing, Epigenetics Cancer Aging Dis. (2025).

[207]

M. Laisne, M. Lupien, C. Vallot, Epigenomic heterogeneity as a source of tumour evolution, Nat. Rev. Cancer 25 (1) (2025) 7-26.

[208]

E.N. Mendoza, M.R. Ciriolo, F. Ciccarone, Hypoxia-Induced Reactive Oxygen Species: Their Role in Cancer Resistance and Emerging Therapies to Overcome It, Antioxid. (Basel) 14 (1) (2025).

[209]

S.K. Rehman, et al., Colorectal Cancer Cells Enter a Diapause-like DTP State to Survive Chemotherapy, Cell 184 (1) (2021) 226-242 e21.

[210]

Y. Naoi, et al., CD106 in Tumor-Specific Exhausted CD8+ T Cells Mediates Immunosuppression by Inhibiting TCR Signaling, Cancer Res 84 (13) (2024) 2109-2122.

[211]

W. Ding, et al., Metabolic reprogramming of tumor-associated macrophages via adenosine-A(2A)R signaling drives cross-resistance in non-small cell lung cancer, Drug Resist Updat 82 (2025) 101272.

[212]

C.C. Zebley, et al., T cell dysfunction and therapeutic intervention in cancer, Nat. Immunol. 25 (8) (2024) 1344-1354.

[213]

J. Kwon, S.F. Bakhoum, The Cytosolic DNA-Sensing cGAS-STING Pathway in Cancer, Cancer Discov. 10 (1) (2020) 26-39.

[214]

Y.H. Chen, et al., TRABID inhibition activates cGAS/STING-mediated anti-tumor immunity through mitosis and autophagy dysregulation, Nat. Commun. 14 (1) (2023) 3050.

[215]

J. Li, et al., cGAS-ISG15-RAGE axis reprogram necroptotic microenvironment and promote lymphatic metastasis in head and neck cancer, Exp. Hematol. Oncol. 13 (1) (2024) 63.

[216]

L. Jingyuan, et al., Matrix stiffness induces an invasive-dormant subpopulation via cGAS-STING axis in oral cancer, Transl. Oncol. 33 (2023) 101681.

[217]

C. Hong, et al., cGAS-STING drives the IL-6-dependent survival of chromosomally instable cancers, Nature 607 (7918) (2022) 366-373.

[218]

J. Li, et al., Non-cell-autonomous cancer progression from chromosomal instability, Nature 620 (7976) (2023) 1080-1088.

[219]

S. Yu, et al., Nanosized Shikonin Disrupts Tumor-Cell Mismatch Repair and Synergizes with Manganese to Sensitize Squamous Carcinoma to Immunotherapy, ACS Nano 19 (14) (2025) 13889-13905.

[220]

J. Cai, et al., Lactylation-Driven NUPR1 Promotes Immunosuppression of Tumor-Infiltrating Macrophages in Hepatocellular Carcinoma, Adv. Sci. (Weinh.) 12 (20) (2025) e2413095.

[221]

Y. Li, et al., SHP2 deneddylation mediates tumor immunosuppression in colon cancer via the CD47/SIRPα axis, J. Clin. Invest 133 (4) (2023).

[222]

Z. Zhou, et al., Tumor-intrinsic SIRPA promotes sensitivity to checkpoint inhibition immunotherapy in melanoma, Cancer Cell 40 (11) (2022) 1324-1340.e8.

[223]

E. Panieri, M.M. Santoro, ROS homeostasis and metabolism: a dangerous liason in cancer cells, Cell Death Dis. 7 (6) (2016) e2253.

[224]

K.A. Conklin, Chemotherapy-associated oxidative stress: impact on chemotherapeutic effectiveness, Integr. Cancer Ther. 3 (4) (2004) 294-300.

[225]

P. Panneerselvan, et al., Insights on the functional dualism of nitric oxide in the hallmarks of cancer, Biochim Biophys. Acta Rev. Cancer 1878 (6) (2023) 189001.

[226]

Z. Jiang, et al., A NIR-II Photoacoustic Probe for High Spatial Quantitative Imaging of Tumor Nitric Oxide in Vivo, Angew. Chem. Int Ed. Engl. 63 (19) (2024) e202320072.

[227]

L. Morbidelli, Therapeutic Potential of Nitric Oxide Donors in Cancer: Focus on Angiogenesis, Crit. Rev. Oncog. 21 (5-6) (2016) 447-458.

[228]

Y. Feng, et al., Nitrate increases cisplatin chemosensitivity of oral squamous cell carcinoma via REDD1/AKT signaling pathway, Sci. China Life Sci. 64 (11) (2021) 1814-1828.

[229]

L.J. Frederiksen, et al., Hypoxia induced resistance to doxorubicin in prostate cancer cells is inhibited by low concentrations of glyceryl trinitrate, J. Urol. 170 (3) (2003) 1003-1007.

[230]

L. Rishi, et al., Nitric oxide induces apoptosis in cutaneous T cell lymphoma (HuT-78) by downregulating constitutive NF-kappaB. Biochim Biophys Acta, 1770 (8) (2007) 1230-1239.

[231]

S. Chang, et al., Inorganic Nitrate Alleviates Total Body Irradiation-Induced Systemic Damage by Decreasing Reactive Oxygen Species Levels, Int J. Radiat. Oncol. Biol. Phys. 103 (4) (2019) 945-957.

[232]

W. Wang, et al., Total body irradiation-induced colon damage is prevented by nitrate-mediated suppression of oxidative stress and homeostasis of the gut microbiome, Nitric Oxide 102 (2020) 1-11.

[233]

T. Yang, et al., The Effects of Mesenchymal Stem Cells on Oral Cancer and Possible Therapy Regime, Front Genet 13 (2022) 949770.

[234]

P. Liu, et al., Exosomes derived from stem cells of human deciduous exfoliated teeth inhibit angiogenesis in vivo and in vitro via the transfer of miR-100-5p and miR-1246, Stem Cell Res Ther. 13 (1) (2022) 89.

[235]

X. Ji, et al., Mesenchymal stem cells derived from normal gingival tissue inhibit the proliferation of oral cancer cells in vitro and in vivo, Int J. Oncol. 49 (5) (2016) 2011-2022.

[236]

L. Zhang, et al., Targeting Breast Cancer Stem Cells, Int J. Biol. Sci. 19 (2) (2023) 552-570.

[237]

Z. Weng, et al., Therapeutic roles of mesenchymal stem cell-derived extracellular vesicles in cancer, J. Hematol. Oncol. 14 (1) (2021) 136.

[238]

S. Wang, et al., Can precancerous stem cells be risk markers for malignant transformation in the oral mucosa? Cell Mol. Biol. Lett. 28 (1) (2023) 30.

[239]

X. Wang, et al., Endothelial mechanobiology in atherosclerosis, Cardiovasc Res 119 (8) (2023) 1656-1675.

[240]

W.L. Wang, et al., Impacts of aging and fluid shear stress on vascular endothelial metabolism and atherosclerosis development, J. Biomed. Sci. 32 (1) (2025) 83.

[241]

K.S. Heo, et al., Mechanistic insights and emerging therapeutic strategies targeting endothelial dysfunction in cardiovascular diseases, Arch. Pharm. Res 48 (4) (2025) 305-332.

[242]

O. Berillo, P. Paradis, E.L. Schiffrin, Role of Immune Cells in Perivascular Adipose Tissue in Vascular Injury in Hypertension, Arterioscler. Thromb. Vasc. Biol. 45 (5) (2025) 563-575.

[243]

J.O. Lundberg, M.T. Gladwin, E. Weitzberg, Strategies to increase nitric oxide signalling in cardiovascular disease, Nat. Rev. Drug Discov. 14 (9) (2015) 623-641.

[244]

D.A. Hobbs, T.W. George, J.A. Lovegrove, The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies, Nutr. Res Rev. 26 (2) (2013) 210-222.

[245]

V. Kapil, et al., Dietary nitrate provides sustained blood pressure lowering in hypertensive patients: a randomized, phase 2, double-blind, placebo-controlled study, Hypertension 65 (2) (2015) 320-327.

[246]

A.J. Webb, et al., Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite, Hypertension 51 (3) (2008) 784-790.

[247]

S. Velmurugan, et al., Dietary nitrate improves vascular function in patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled study, Am. J. Clin. Nutr. 103 (1) (2016) 25-38.

[248]

J.R. Bakker, et al., Low dose dietary nitrate improves endothelial dysfunction and plaque stability in the ApoE(-/-) mouse fed a high fat diet, Free Radic. Biol. Med 99 (2016) 189-198.

[249]

J. Eggebeen, et al., One Week of Daily Dosing With Beetroot Juice Improves Submaximal Endurance and Blood Pressure in Older Patients With Heart Failure and Preserved Ejection Fraction, JACC Heart Fail 4 (6) (2016) 428-437.

[250]

A.R. Coggan, et al., Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients With Heart Failure: A Double-Blind, Placebo-Controlled, Randomized Trial, Circ. Heart Fail 8 (5) (2015) 914-920.

[251]

J.M. Tarkin, J.C. Kaski, Vasodilator Therapy: Nitrates and Nicorandil, Cardiovasc Drugs Ther. 30 (4) (2016) 367-378.

[252]

T. Münzel, A. Daiber, A. Mülsch, Explaining the phenomenon of nitrate tolerance, Circ. Res 97 (7) (2005) 618-628.

[253]

C. Koliaki, et al., The Implication of Gut Hormones in the Regulation of Energy Homeostasis and Their Role in the Pathophysiology of Obesity, Curr. Obes. Rep. 9 (3) (2020) 255-271.

[254]

M.A. Rossi, G.D. Stuber, Overlapping Brain Circuits for Homeostatic and Hedonic Feeding, Cell Metab. 27 (1) (2018) 42-56.

[255]

T.V. Rohm, et al., Inflammation in obesity, diabetes, and related disorders, Immunity 55 (1) (2022) 31-55.

[256]

T. Kawai, M.V. Autieri, R. Scalia, Adipose tissue inflammation and metabolic dysfunction in obesity, Am. J. Physiol. Cell Physiol. 320 (3) (2021) C375-c391.

[257]

Z. Bahadoran, et al., Inorganic nitrate, a natural anti-obesity agent: A systematic review and meta-analysis of animal studies, Excli J. 19 (2020) 972-983.

[258]

I. Cordero-Herrera, et al., AMP-activated protein kinase activation and NADPH oxidase inhibition by inorganic nitrate and nitrite prevent liver steatosis, Proc. Natl. Acad. Sci. USA 116 (1) (2019) 217-226.

[259]

A.H. de Mello, et al., Mitochondrial dysfunction in obesity, Life Sci. 192 (2018) 26-32.

[260]

L.D. Roberts, et al., Inorganic nitrate promotes the browning of white adipose tissue through the nitrate-nitrite-nitric oxide pathway, Diabetes 64 (2) (2015) 471-484.

[261]

L. Ma, et al., Rebalancing glucolipid metabolism and gut microbiome dysbiosis by nitrate-dependent alleviation of high-fat diet-induced obesity, BMJ Open Diabetes Res Care 8 (1) (2020).

[262]

M. Carlström, et al., Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice, Proc. Natl. Acad. Sci. USA 107 (41) (2010) 17716-17720.

[263]

S. Khalifi, et al., Dietary nitrate improves glucose tolerance and lipid profile in an animal model of hyperglycemia, Nitric Oxide 44 (2015) 24-30.

[264]

T.A. Schiffer, et al., Modulation of mitochondria and NADPH oxidase function by the nitrate-nitrite-NO pathway in metabolic disease with focus on type 2 diabetes, Biochim Biophys. Acta Mol. Basis Dis. 1866 (8) (2020) 165811.

[265]

P. Carter, et al., Fruit and vegetable intake and incidence of type 2 diabetes mellitus: systematic review and meta-analysis, Bmj 341 (2010) c4229.

[266]

K.J. Joshipura, et al., Over-the-counter mouthwash use and risk of pre-diabetes/diabetes, Nitric Oxide 71 (2017) 14-20.

[267]

W. Pan, et al., Nanonitrator: novel enhancer of inorganic nitrate's protective effects, predicated on swarm learning approach, Sci. Bull. (Beijing) 68 (8) (2023) 838-850.

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