1. Introduction
2. Pathophysiological and Clinical Aspects in Sepsis
3. Biochemical Aspects of Cannabinoids
4. The Expression of Cannabinoid Signaling System in Sepsis
5. The Cannabinoid Signaling System and Inflammation-Linked with Sepsis
6. Cannabinoid Signaling System and Redox Activity-Linked with Sepsis
7. MicroRNAs Expression in Sepsis-Induced by Cannabinoid Signaling System
8. Immune System Expression-Induced by Cannabinoid Signaling System
9. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Angus, D.C.; van der Poll, T.; Wacker, D.A.; Winters, M.E.; Finfer, S.R.; Vincent, J.-L.; De Backer, D.; Martin, G.S.; Mutschler, M.; Paffrath, T.; et al. Severe sepsis and septic shock. Emerg. Med. Clin. N. Am. 2013, 45 (Suppl. 3), 747–758. [Google Scholar] [CrossRef] [PubMed]
- Coelho, F.R.; Martins, J.O. Diagnostic methods in sepsis: The need of speed. Rev. Assoc. Med. Bras. 2012, 58, 498–504. [Google Scholar] [CrossRef]
- David, V.L.; Ercisli, F.; Florin, A.; Boia, E.S.; Nitu, R. Early Prediction of Sepsis Incidence in Critically Ill Patients Using Specific Genetic Polymorphisms. Biochem. Genet. 2017, 55, 193–203. [Google Scholar] [CrossRef] [PubMed]
- Abraham, E. NF-κB activation. Crit. Care Med. 2000, 28, N100–N104. [Google Scholar] [CrossRef]
- Cimolai, M.C.; Alvarez, S.; Bode, C.; Bugger, H. Mitochondrial Mechanisms in Septic Cardiomyopathy. Int. J. Mol. Sci. 2015, 16, 17763–17778. [Google Scholar] [CrossRef]
- Horhat, F.G.; Gundogdu, F.; David, L.V.; Boia, E.S.; Pirtea, L.; Horhat, R.; Cucui-Cozma, A.; Ciuca, I.; Diaconu, M.; Nitu, R.; et al. Early Evaluation and Monitoring of Critical Patients with Acute Respiratory Distress Syndrome (ARDS) Using Specific Genetic Polymorphisms. Biochem. Genet. 2017, 55, 204–211. [Google Scholar] [CrossRef]
- Koekkoek, W.A.C.; van Zanten, A.R.H. Antioxidant Vitamins and Trace Elements in Critical Illness. Nutr. Clin. Pract. 2016, 31, 457–474. [Google Scholar] [CrossRef]
- Akinosoglou, K.; Alexopoulos, D. Use of antiplatelet agents in sepsis: A glimpse into the future. Thromb. Res. 2014, 133, 131–138. [Google Scholar] [CrossRef]
- Pop-Began, V.; Păunescu, V.; Grigorean, V.; Pop-Began, D.; Popescu, C. Molecular mechanisms in the pathogenesis of sepsis. J. Med. Life 2014, 7, 38–41. [Google Scholar]
- Xie, L.X. New biomarkers for sepsis. Med. J. Chin. People’s Lib. Army 2013, 38, 6–9. [Google Scholar]
- Bartz, R.R.; Fu, P.; Suliman, H.B.; Crowley, S.D.; MacGarvey, N.C.; Welty-Wolf, K.; Piantadosi, C.A. Staphylococcus aureus sepsis induces early renal mitochondrial DNA repair and mitochondrial biogenesis in mice. PLoS ONE 2014, 9, e100912. [Google Scholar] [CrossRef] [PubMed]
- Id, A.S.; Theilla, M.; Hellerman, M.; Singer, P.; Maggiore, U.; Barbagallo, M.; Regolisti, G.; Fiaccadori, E. Energy and Protein in Critically Ill Patients with AKI: A Prospective, Multicenter Observational Study Using Indirect Calorimetry and Protein Catabolic Rate. Nutrients 2017, 9, 802. [Google Scholar]
- Daniel Lafreniere, J.; Lehmann, C. Parameters of the endocannabinoid system as novel biomarkers in sepsis and septic shock. Metabolites 2017, 7, 55. [Google Scholar] [CrossRef] [PubMed]
- Rogobete, A.F.; Sandesc, D.; Bedreag, O.H.; Papurica, M.; Popovici, S.E.; Bratu, T.; Popoiu, C.M.; Nitu, R.; Dragomir, T.; AAbed, H.I.M.; et al. MicroRNA Expression is Associated with Sepsis Disorders in Critically Ill Polytrauma Patients. Cells 2018, 7, 271. [Google Scholar] [CrossRef] [PubMed]
- Meza, A.; Lehmann, C. Betacaryophyllene—A phytocannabinoid as potential therapeutic modality for human sepsis? Med. Hypotheses 2018, 110, 68–70. [Google Scholar] [CrossRef]
- Chiarlone, A.; Börner, C.; Martín-Gómez, L.; Jiménez-González, A.; García-Concejo, A.; García-Bermejo, M.L.; Lorente, M.; Blázquez, C.; García-Taboada, E.; de Haro, A.; et al. MicroRNA let-7d is a target of cannabinoid CB1 receptor and controls cannabinoid signaling. Neuropharmacology 2016, 108, 345–352. [Google Scholar] [CrossRef]
- Fox, E.D.; Heffernan, D.S.; Cioffi, W.G.; Reichner, J.S. Neutrophils from critically ill septic patients mediate profound loss of endothelial barrier integrity. Crit. Care 2013, 17, R226. [Google Scholar] [CrossRef]
- Gu, W.; Jiang, J. Genetic polymorphisms and posttraumatic complications. Comp. Funct. Genom. 2010, 2010. [Google Scholar] [CrossRef]
- Wenceslau, C.F.; McCarthy, C.G.; Goulopoulou, S.; Szasz, T.; NeSmith, E.G.; Webb, R.C. Mitochondrial-derived N-formyl peptides: Novel links between trauma, vascular collapse and sepsis. Med. Hypotheses 2013, 81, 532–535. [Google Scholar] [CrossRef]
- Huber-Lang, M.; Kovtun, A.; Ignatius, A. The role of complement in trauma and fracture healing. Semin. Immunol. 2013, 25, 73–78. [Google Scholar] [CrossRef]
- Sun, S.; Sursal, T.; Adibnia, Y.; Zhao, C.; Zheng, Y.; Li, H.; Otterbein, L.E.; Hauser, C.J.; Itagaki, K. Mitochondrial DAMPs Increase Endothelial Permeability through Neutrophil Dependent and Independent Pathways. PLoS ONE 2013, 8, e59989. [Google Scholar] [CrossRef] [PubMed]
- Romero, R.; Chaiworapongsa, T.; Alpay Savasan, Z.; Xu, Y.; Hussein, Y.; Dong, Z.; Kusanovic, J.P.; Kim, C.J.; Hassan, S.S. Damage-associated molecular patterns (DAMPs) in preterm labor with intact membranes and preterm PROM: A study of the alarmin HMGB1. J. Matern.-Fetal Neonatal Med. 2011, 24, 1444–1455. [Google Scholar] [CrossRef] [PubMed]
- Bronkhorst, M.W.G.A.; Boyé, N.D.A.; Lomax, M.A.Z.; Vossen, R.H.A.M.; Bakker, J.; Patka, P.; Van Lieshout, E.M.M. Single-nucleotide polymorphisms in the Toll-like receptor pathway increase susceptibility to infections in severely injured trauma patients. J. Trauma Acute Care Surg. 2013, 74, 862–870. [Google Scholar] [CrossRef] [PubMed]
- Sutherland, A.M.; Walley, K.R.; Russell, J.A. Polymorphisms in CD14, mannose-binding lectin, and Toll-like receptor-2 are associated with increased prevalence of infection in critically ill adults*. Crit. Care Med. 2005, 33, 638–644. [Google Scholar] [CrossRef]
- Szilágyi, B.; Fejes, Z.; Pócsi, M.; Kappelmayer, J.; Nagy, B., Jr. Role of sepsis modulated circulating microRNAs. EJIFCC 2019, 30, 128–145. [Google Scholar]
- Davis, S.M.; Clark, E.A.S.; Nelson, L.T.; Silver, R.M. The association of innate immune response gene polymorphisms and puerperal group a streptococcal sepsis. Am. J. Obstet. Gynecol. 2010, 202, 308 e1–308 e8. [Google Scholar] [CrossRef]
- Stanilova, S.A.; Miteva, L.D.; Karakolev, Z.T.; Stefanov, C.S. Interleukin-10-1082 promoter polymorphism in association with cytokine production and sepsis susceptibility. Intensive Care Med. 2006, 32, 260–266. [Google Scholar] [CrossRef]
- Unit, I.C.; Paz, H. La Interleukin-1 receptor antagonist gene polymorphism and mortality in patients with severe sepsis. Clin. Exp. Immunol. 2002, 127, 331–336. [Google Scholar]
- Das, U.N. Serum adipocyte fatty acid-binding protein in the critically ill. Crit. Care 2013, 17, 121. [Google Scholar] [CrossRef]
- Kołakowska, B. Nutrition challenges in polytrauma patients. New trends in energy expenditure measurements. Central European J. of Clin. Res. 2019, 2, 51–57. [Google Scholar] [CrossRef]
- Pravda, J. Metabolic theory of septic shock. World J. Crit. Care Med. 2014, 3, 45–54. [Google Scholar] [CrossRef] [PubMed]
- Papadopoulos, M.C.; Davies, D.C.; Moss, R.F.; Tighe, D.; Bennett, E.D. Pathophysiology of septic encephalopathy: A review. Crit. Care Med. 2000, 28, 3019–3024. [Google Scholar] [CrossRef] [PubMed]
- Malbrain, M.L.N.G.; Marik, P.E.; Witters, I.; Cordemans, C.; Kirkpatrick, A.W.; Roberts, D.J.; Van Regenmortel, N. Fluid overload, de-resuscitation, and outcomes in critically ill or injured patients: A systematic review with suggestions for clinical practice. Anaesthesiol. Intensive Ter. 2014, 46, 361–380. [Google Scholar] [CrossRef] [PubMed]
- Oudemans-van Straaten, H.M.; Man, A.M.S.; de Waard, M.C. Vitamin C revisited. Crit. Care 2014, 18, 460. [Google Scholar] [CrossRef]
- Gill, S.E.; Rohan, M.; Mehta, S. Role of pulmonary microvascular endothelial cell apoptosis in murine sepsis-induced lung injury in vivo. Respir. Res. 2015, 16, 109. [Google Scholar] [CrossRef] [PubMed]
- Biron, B.M.; Ayala, A.; Lomas-neira, J.L. Biomarkers for Sepsis: What Is and What Might Be? Biomark Insights. 2015, 10, 7–17. [Google Scholar] [CrossRef]
- Binkowska, A.M.; Michalak, G.; Słotwiński, R. Current views on the mechanisms of immune responses to trauma and infection. Cent.-Eur. J. Immunol. 2015, 40, 206–216. [Google Scholar] [CrossRef]
- Leite, H.P.; de Lima, L.F.P. Metabolic resuscitation in sepsis: A necessary step beyond the hemodynamic? J. Thorac. Dis. 2016, 8, E552–E557. [Google Scholar] [CrossRef]
- Arlati, S.; Storti, E.; Pradella, V.; Bucci, L.; Vitolo, A.; Pulici, M. Decreased fluid volume to reduce organ damage: A new approach to burn shock resuscitation? A preliminary study. Resuscitation 2007, 72, 371–378. [Google Scholar] [CrossRef]
- Iseppi, R.; Brighenti, V.; Licata, M.; Lambertini, A.; Sabia, C.; Messi, P.; Pellati, F.; Benvenuti, S. Chemical characterization and evaluation of the antibacterial activity of essential oils from fibre-type cannabis sativa L. (Hemp). Molecules 2019, 24, 7–12. [Google Scholar] [CrossRef]
- Khuja, I.; Yekhtin, Z.; Or, R.; Almogi-Hazan, O. Cannabinoids reduce inflammation but inhibit lymphocyte recovery in murine models of bone marrow transplantation. Int. J. Mol. Sci. 2019, 20, 668. [Google Scholar] [CrossRef] [PubMed]
- Alexander, A.; Smith, P.F.; Rosengren, R.J. Cannabinoids in the treatment of cancer. Cancer Lett. 2009, 285, 6–12. [Google Scholar] [CrossRef] [PubMed]
- Chiurchiu, V.; Leuti, A.; Cencioni, M.T.; Albanese, M.; De Bardi, M.; Bisogno, T.; Centonze, D.; Battistini, L.; Maccarrone, M. Modulation of monocytes by bioactive lipid anandamide in multiple sclerosis involves distinct Toll-like receptors. Pharmacol. Res. 2016, 113, 313–319. [Google Scholar] [CrossRef] [PubMed]
- Leishman, E.; Murphy, M.; Mackie, K.; Bradshaw, H.B. BBA—Molecular and Cell Biology of Lipids Δ9-Tetrahydrocannabinol changes the brain lipidome and transcriptome di ff erentially in the adolescent and the adult. BBA-Mol. Cell Biol. Lipids 2018, 1863, 479–492. [Google Scholar] [CrossRef] [PubMed]
- Chiurchiu, V.; Cencioni, M.T.; Bisicchia, E.; De Bardi, M.; Gasperini, C.; Borsellino, G.; Centonze, D.; Battistini, L.; Maccarrone, M. Distinct modulation of human myeloid and plasmacytoid dendritic cells by anandamide in multiple sclerosis. Ann. Neurol. 2013, 73, 626–636. [Google Scholar] [CrossRef] [PubMed]
- Matthews, A.T.; Ross, M.K. Oxyradical Stress, Endocannabinoids, and Atherosclerosis. Toxics 2015, 3, 481–498. [Google Scholar] [CrossRef] [PubMed]
- Chanda, D.; Kim, D.-K.; Li, T.; Kim, Y.-H.; Koo, S.-H.; Lee, C.-H.; Chiang, J.Y.L.; Choi, H.-S. Cannabinoid receptor type 1 (CB1R) signaling regulates hepatic gluconeogenesis via induction of endoplasmic reticulum-bound transcription factor cAMP-responsive element-binding protein H (CREBH) in primary hepatocytes. J. Biol. Chem. 2011, 286, 27971–27979. [Google Scholar] [CrossRef]
- Bisogno, T.; Ligresti, A.; Di Marzo, V. The endocannabinoid signalling system: Biochemical aspects. Pharmacol. Biochem. Behav. 2005, 81, 224–238. [Google Scholar] [CrossRef]
- Silvestri, C.; Di Marzo, V. The Endocannabinoid System in Energy Homeostasis and the Etiopathology of Metabolic Disorders. Cell Metab. 2013, 17, 475–490. [Google Scholar] [CrossRef]
- Maione, S.; Costa, B.; Di Marzo, V. Endocannabinoids: A unique opportunity to develop multitarget analgesics. PAIN 2013, 154, S87–S93. [Google Scholar] [CrossRef]
- Di Marzo, V. Targeting the endocannabinoid system: To enhance or reduce? Nat. Rev. Drug Discov. 2008, 7, 438–455. [Google Scholar] [CrossRef] [PubMed]
- Mechoulam, R.; Parker, L.A. The Endocannabinoid System and the Brain. Annu. Rev. Psychol. 2013, 64, 21–47. [Google Scholar] [CrossRef] [PubMed]
- McHugh, D.; Tanner, C.; Mechoulam, R.; Pertwee, R.G.; Ross, R.A. Inhibition of Human Neutrophil Chemotaxis by Endogenous Cannabinoids and Phytocannabinoids: Evidence for a Site Distinct from CB1 and CB2. Mol. Pharmacol. 2008, 73, 441–450. [Google Scholar] [CrossRef] [PubMed]
- Tabarkiewicz, J. Endocannabinoid system as a regulator of tumor cell malignancy—Biological pathways and clinical significance. Onco Targets Ther. 2016, 9, 4323–4336. [Google Scholar]
- Gardner, E.L. Endocannabinoid signaling system and brain reward: Emphasis on dopamine. Pharmacol. Biochem. Behav. 2005, 81, 263–284. [Google Scholar] [CrossRef]
- Watkins, B.A.; Hutchins, H.; Li, Y.; Seifert, M.F. The endocannabinoid signaling system: A marriage of PUFA and musculoskeletal health. J. Nutr. Biochem. 2010, 21, 1141–1152. [Google Scholar] [CrossRef]
- Dogjani, A.; Zatriqi, S.; Uranues, S.; Latifi, R. Biology-based nutritional support of critically ill and injured patients. Eur. Surg. 2011, 43, 7–12. [Google Scholar] [CrossRef]
- Vallejo, K.P.; Martínez, C.M.; Adames, A.A.M.; Fuchs-tarlovsky, V.; Carlos, G.; Nogales, C.; Enrique, R.; Paz, R.; Perman, M.I.; Isabel, M.; et al. Current clinical nutrition practices in critically ill patients in Latin America: A multinational observational study. Crit. Care 2017, 21, 227. [Google Scholar] [CrossRef]
- Maday, K.R. Energy Estimation in the Critically Ill: A Literature Review. Int. J. Clin. Med. 2013, 1, 39–43. [Google Scholar]
- Rogobete, A.F.; Sandesc, D.; Papurica, M.; Stoicescu, E.R.; Popovici, S.E.; Bratu, L.M.; Vernic, C.; Sas, A.M.; Stan, A.T.; Bedreag, O.H. The influence of metabolic imbalances and oxidative stress on the outcome of critically ill polytrauma patients: A review. Burn. Trauma 2017, 5, 8. [Google Scholar] [CrossRef]
- Mecha, M.; Torrao, A.S.; Mestre, L.; Carrillo-salinas, F.J.; Mechoulam, R.; Guaza, C. Cannabidiol protects oligodendrocyte progenitor cells from inflammation-induced apoptosis by attenuating endoplasmic reticulum stress. Cell Death Discov. 2012, 3, e331. [Google Scholar] [CrossRef]
- Simon, L.; Song, K.; Stouwe, C.V.; Hollenbach, A.; Amedee, A.; Mohan, M.; Winsauer, P.; Molina, P. Δ9-Tetrahydrocannabinol (Δ9-THC) Promotes Neuroimmune-Modulatory MicroRNA Profile in Striatum of Simian Immunodeficiency Virus (SIV)-Infected Macaques. J. Neuroimmune Pharmacol. 2016, 11, 192–213. [Google Scholar] [CrossRef] [PubMed]
- Mechoulam, R.; Peters, M.; Murillo-Rodriguez, E.; Hanus, L.O. Cannabidiol--recent advances. Chem. Biodivers. 2007, 4, 1678–1692. [Google Scholar] [CrossRef] [PubMed]
- Brown, I.; Cascio, M.G.; Rotondo, D.; Pertwee, R.G.; Heys, S.D.; Wahle, K.W.J. Cannabinoids and omega-3/6 endocannabinoids as cell death and anticancer modulators. Prog. Lipid Res. 2013, 52, 80–109. [Google Scholar] [CrossRef]
- Palomba, L.; Silvestri, C.; Imperatore, R.; Morello, G.; Piscitelli, F.; Martella, A.; Cristino, L.; Marzo, V. Di Negative Regulation of Leptin-induced Reactive Oxygen Species (ROS) Formation by Cannabinoid CB 1 Receptor Activation in Hypothalamic Neurons. J. Biol. Chem. 2015, 290, 13669–13677. [Google Scholar] [CrossRef]
- Lau, F.C.; Bagchi, M.; Sen, C.; Roy, S.; Bagchi, D. Nutrigenomic Analysis of Diet-Gene Interactions on Functional Supplements for Weight Management. Curr. Genom. 2008, 9, 239–251. [Google Scholar] [CrossRef]
- Endocannabinoids, S.C.; Mukhopadhyay, P.; Horiguchi, N.; Jeong, W.; Osei-hyiaman, D.; Park, O.; Liu, J.; Harvey-white, J.; Marsicano, G.; Lutz, B.; et al. Paracrine Activation of Hepatic CB1 Receptors Mediates Alcoholic Fatty Liver. Cell. Metab. 2008, 7, 227–235. [Google Scholar]
- Prester, L.; Mikoli, A.; Juri, A.; Fuchs, N.; Neuberg, M.; Luci, A.; Br, I. Chemico-Biological Interactions Effects of Δ9-tetrahydrocannabinol on irinotecan-induced clinical effects in rats. Chem.-Biol. Interact. 2018, 294, 128–134. [Google Scholar] [CrossRef]
- Bruni, N.; Della Pepa, C.; Oliaro-Bosso, S.; Pessione, E.; Gastaldi, D.; Dosio, F. Cannabinoid delivery systems for pain and inflammation treatment. Molecules 2018, 23, 2478. [Google Scholar] [CrossRef]
- Ladak, N.; Beishon, L.; Thompson, J.P.; Lambert, D.G. Trends in Anaesthesia and Critical Care Cannabinoids and sepsis. Trends Anaesth. Crit. Care 2011, 1, 191–198. [Google Scholar] [CrossRef]
- Malfait, A.M.; Gallily, R.; Sumariwalla, P.F.; Malik, A.S.; Andreakos, E.; Mechoulam, R.; Feldmann, M. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc. Natl. Acad. Sci. USA 2000, 97, 9561–9566. [Google Scholar] [CrossRef] [PubMed]
- Esposito, G.; Scuderi, C.; Valenza, M.; Togna, G.I.; Latina, V.; Iuvone, T.; Steardo, L.; De Filippis, D.; Cipriano, M.; Carratu, M.R. Cannabidiol Reduces Aβ-Induced Neuroinflammation and Promotes Hippocampal Neurogenesis through PPARγ Involvement. PLoS ONE 2011, 6, e28668. [Google Scholar] [CrossRef] [PubMed]
- Ribeiro, A.M.; Homsi, C.; Ferreira, J.; Mateus-vasconcelos, E.C.L.; Moroni, R.M.; Maria, L.; Brito, O.; Gustavo, L.; Brito, O. Case Report Physical Therapy in the Management of Pelvic Floor Muscles Hypertonia in a Woman with Hereditary Spastic Paraplegia. Case Rep. Obstet. Gynecol. 2014, 2014, 306028. [Google Scholar]
- Ruiz-valdepeñas, L.; Martínez-orgado, J.A.; Benito, C.; Millán, Á.; Tolón, R.M. Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: An intravital microscopy study Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: An intravital micros. J. Neuroinflamm. 2011, 8, 5. [Google Scholar] [CrossRef] [PubMed]
- Chen, W.; Kaplan, B.L.F.; Pike, S.T.; Topper, L.A.; Lichorobiec, N.R.; Simmons, S.O.; Ramabhadran, R.; Kaminski, N.E. Magnitude of stimulation dictates the cannabinoid-mediated differential T cell response to HIVgp120. J. Leukoc. Biol. 2012, 92, 1093–1102. [Google Scholar] [CrossRef]
- Cassol, O.J., Jr.; Comim, C.M.; Silva, B.R.; Hermani, F.V.; Constantino, L.S.; Felisberto, F.; Petronilho, F.; Hallak, J.E.C.; De Martinis, B.S.; Zuardi, A.W.; et al. Treatment with cannabidiol reverses oxidative stress parameters, cognitive impairment and mortality in rats submitted to sepsis by cecal ligation and puncture. Brain Res. 2010, 1348, 128–138. [Google Scholar] [CrossRef]
- Vuolo, F.; Petronilho, F.; Sonai, B.; Ritter, C.; Hallak, J.E.C.; Zuardi, A.W.; Crippa, J.A.; Dal-pizzol, F. Evaluation of Serum Cytokines Levels and the Role of Cannabidiol Treatment in Animal Model of Asthma. Mediat. Inflamm. 2015, 2015, 538670. [Google Scholar] [CrossRef]
- Nissen, L.; Zatta, A.; Stefanini, I.; Grandi, S.; Sgorbati, B.; Biavati, B.; Monti, A. Characterization and antimicrobial activity of essential oils of industrial hemp varieties (Cannabis sativa L.). Fitoterapia 2010, 81, 413–419. [Google Scholar] [CrossRef]
- Hernández-cervantes, R.; Méndez-díaz, M.; Prospéro-garcía, Ó. Immunoregulatory Role of Cannabinoids during Infectious Disease. Neuroimmunomodulation 2017, 24, 183–199. [Google Scholar] [CrossRef]
- Wasim, K.; Haq, I.; Ashraf, M. Antimicrobial studies of the leaf of cannabis sativa L. Pak. J. Pharm. Sci. 1995, 8, 29–38. [Google Scholar]
- Elphick, M.R. BfCBR: A cannabinoid receptor ortholog in the cephalochordate Branchiostoma floridae (Amphioxus). Gene 2007, 399, 65–71. [Google Scholar] [CrossRef] [PubMed]
- Appendino, G.; Gibbons, S.; Giana, A.; Pagani, A.; Grassi, G.; Stavri, M.; Smith, E.; Rahman, M.M. Antibacterial cannabinoids from Cannabis sativa: A structure-activity study. J. Nat. Prod. 2008, 71, 1427–1430. [Google Scholar] [CrossRef] [PubMed]
- Bass, R.; Engelhard, D.; Trembovler, V.; Shohami, E. A novel nonpsychotropic cannabinoid, HU-211, in the treatment of experimental pneumococcal meningitis. J. Infect. Dis. 1996, 173, 735–738. [Google Scholar] [CrossRef] [PubMed]
- Chakraborty, S.; Bisoi, S.; Chattopadhyay, D.; Mishra, R. A Study on Demographic and Clinical Profile of Burn Patients in an Apex Institute of West Bengal. Indian J. Public Health. 2010, 54, 92–94. [Google Scholar]
- Bellocchio, L.; Lafenetre, P.; Cannich, A.; Cota, D.; Puente, N.; Grandes, P.; Chaouloff, F.; Piazza, P.V.; Marsicano, G. Bimodal control of stimulated food intake by the endocannabinoid system. Nat. Neurosci. 2010, 13, 281–283. [Google Scholar] [CrossRef]
- Sardinha, J.; Kelly, M.E.M.; Zhou, J.; Lehmann, C. Experimental Cannabinoid 2 Receptor-Mediated Immune Modulation in Sepsis. Mediat. Inflamm. 2014, 2014, 978678. [Google Scholar] [CrossRef]
- Wang, L.-L.; Zhao, R.; Li, J.-Y.; Li, S.-S.; Liu, M.; Wang, M.; Zhang, M.-Z.; Dong, W.-W.; Jiang, S.-K.; Zhang, M.; et al. Pharmacological activation of cannabinoid 2 receptor attenuates inflammation, fibrogenesis, and promotes re-epithelialization during skin wound healing. Eur. J. Pharmacol. 2016, 786, 128–136. [Google Scholar] [CrossRef]
- Eisenstein, T.K.; Meissler, J.J. Effects of Cannabinoids on T-cell Function and Resistance to Infection. J. Neuroimmune Pharmacol. 2015, 10, 204–216. [Google Scholar] [CrossRef]
- Ribeiro, A.; Ferraz-de-Paula, V.; Pinheiro, M.L.; Vitoretti, L.B.; Mariano-Souza, D.P.; Quinteiro-Filho, W.M.; Akamine, A.T.; Almeida, V.I.; Quevedo, J.; Dal-Pizzol, F.; et al. Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases inflammation in a murine model of acute lung injury: Role for the adenosine A2A receptor. Eur. J. Pharmacol. 2012, 678, 78–85. [Google Scholar] [CrossRef]
- Obeid, R.; Herrmann, W. Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett. 2006, 580, 2994–3005. [Google Scholar] [CrossRef]
- Naviaux, R.K. Mitochondrion Metabolic features of the cell danger response. MITOCH 2014, 16, 7–17. [Google Scholar] [CrossRef] [PubMed]
- Horhat, F.G.; Rogobete, A.F.; Papurica, M.; Sandesc, D.; Tanasescu, S.; Dumitrascu, V.; Licker, M.; Nitu, R.; Cradigati, C.A.; Sarandan, M.; et al. The Use of Lipid Peroxidation Expression as a Biomarker for the Molecular Damage in the Critically Ill Polytrauma Patient. Clin. Lab. 2016, 62, 1601–1607. [Google Scholar] [CrossRef] [PubMed]
- Melo, A.C.; Valença, S.S.; Gitirana, L.B.; Santos, J.C.; Ribeiro, L.M.; Machado, M.N.; Magalhães, C.B.; Zin, W.A.; Porto, L.C. Redox markers and inflammation are differentially affected by atorvastatin, pravastatin or simvastatin administered before endotoxin-induced acute lung injury. Int. Immunopharmacol. 2013, 17, 57–64. [Google Scholar] [CrossRef] [PubMed]
- Moise, A. Vitamin D in Critically Ill Patients - From Molecular Damage Interactions to Clinical Outcomes Benefits. When, Why, How? Central. European. J. Clin. Res. 2018, 1, 59–66. [Google Scholar] [CrossRef]
- Sandesc, M.; Rogobete, A.F.; Bedreag, O.H.; Dinu, A.; Papurica, M.; Cradigati, C.A.; Sarandan, M.; Popovici, S.E.; Bratu, L.M.; Bratu, T.; et al. Analysis of oxidative stress-related markers in critically ill polytrauma patients: An observational prospective single-center study. Bosn. J. Basic Med. Sci. 2018, 18, 191–197. [Google Scholar] [CrossRef]
- Bedreag, O.H.; Rogobete, A.F.; Sandesc, D.; Cradigati, C.A.; Sarandan, M.; Popovici, S.E.; Dumache, R.; Horhat, F.G.; Vernic, C.; Sima, L.V.; et al. Modulation of the Redox Expression and Inflammation Response in the Critically Ill Polytrauma Patient with Thoracic Injury. Statistical Correlations between Antioxidant Therapy and Clinical Aspects. A Retrospective Single Center Study. Clin. Lab. 2016, 62, 1747–1759. [Google Scholar] [CrossRef]
- Hu, Y.; Deng, H.; Xu, S.; Zhang, J. MicroRNAs Regulate Mitochondrial Function in Cerebral Ischemia-Reperfusion Injury. Int. J. Mol. Sci. 2015, 16, 24895–24917. [Google Scholar] [CrossRef]
- Fredriksson, K.; Tjäder, I.; Keller, P.; Petrovic, N.; Ahlman, B.; Schéele, C.; Wernerman, J.; Timmons, J.A.; Rooyackers, O. Dysregulation of mitochondrial dynamics and the muscle transcriptome in ICU patients suffering from sepsis induced multiple organ failure. PLoS ONE 2008, 3, e3686. [Google Scholar] [CrossRef]
- Ross, J.A.; Tolar, J.; Spector, L.G.; DeFor, T.; Lund, T.C.; Weisdorf, D.J.; Langer, E.; Hooten, A.J.; Thyagarajan, B.; Gleason, M.K.; et al. An exploratory analysis of mitochondrial haplotypes and allogeneic hematopoietic cell transplantation outcomes. Biol. Blood Marrow Transplant. 2015, 21, 81–88. [Google Scholar] [CrossRef]
- Yao, X.; Carlson, D.; Sun, Y.; Ma, L.; Wolf, S.E.; Minei, J.P.; Zang, Q.S. Mitochondrial ROS induces cardiac inflammation via a pathway through mtDNA damage in a pneumonia-related sepsis model. PLoS ONE 2015, 10, e0139416. [Google Scholar] [CrossRef]
- Liu, X.; Chen, Z. The pathophysiological role of mitochondrial oxidative stress in lung diseases. J. Transl. Med. 2017, 15, 207. [Google Scholar] [CrossRef] [PubMed]
- Sun, S.; Hu, F.; Wu, J.; Zhang, S. Redox Biology Cannabidiol attenuates OGD/R-induced damage by enhancing mitochondrial bioenergetics and modulating glucose metabolism via pentose-phosphate pathway in hippocampal neurons. Redox Biol. 2017, 11, 577–585. [Google Scholar] [CrossRef] [PubMed]
- Burstein, S. Bioorganic & Medicinal Chemistry Cannabidiol (CBD) and its analogs: A review of their effects on inflammation. Bioorg. Med. Chem. 2015, 23, 1377–1385. [Google Scholar] [PubMed]
- Carrier, E.J.; Auchampach, J.A.; Hillard, C.J. Inhibition of an equilibrative nucleoside transporter by cannabidiol: A mechanism of cannabinoid immunosuppression. Proc. Natl. Acad. Sci. USA 2006, 103, 7895–7900. [Google Scholar] [CrossRef] [PubMed]
- Castillo, R.L.; Loza, R.C. Pathophysiological Approaches of Acute Respiratory Distress syndrome: Novel Bases for Study of Lung Injury. Open Respir. Med. J. 2015, 9, 83–91. [Google Scholar] [CrossRef] [PubMed]
- Hebert-Chatelain, E.; Desprez, T.; Serrat, R.; Bellocchio, L.; Soria-Gomez, E.; Busquets-Garcia, A.; Pagano Zottola, A.C.; Delamarre, A.; Cannich, A.; Vincent, P.; et al. A cannabinoid link between mitochondria and memory. Nature 2016, 539, 555. [Google Scholar] [CrossRef] [PubMed]
- Ryan, D.; Drysdale, A.J.; Lafourcade, C.; Pertwee, R.G.; Platt, B. Cannabidiol Targets Mitochondria to Regulate Intracellular Ca+2 Levels. J. Neurosci. 2009, 29, 2053–2063. [Google Scholar] [CrossRef]
- Resstel, L.B.M.; Tavares, R.F.; Lisboa, S.F.S.; Joca, S.R.L.; Corrêa, F.M.A.; Guimarães, F.S. 5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats. Br. J. Pharmacol. 2009, 156, 181–188. [Google Scholar] [CrossRef]
- Nalivaiko, E.; Ootsuka, Y.; Blessing, W.W. Activation of 5-HT1A receptors in the medullary raphe reduces cardiovascular changes elicited by acute psychological and inflammatory stresses in rabbits. Am. J. Physiol. Integr. Comp. Physiol. 2005, 289, R596–R604. [Google Scholar] [CrossRef]
- Mccoy, K.L. Interaction between Cannabinoid System and Toll-Like Receptors Controls Inflammation. Mediat. Inflamm. 2016. [Google Scholar] [CrossRef]
- Kennett, G.A.; Dourish, C.T.; Curzon, G. Antidepressant-like action of 5-HT1A agonists and conventional antidepressants in an animal model of depression. Eur. J. Pharmacol. 1987, 134, 265–274. [Google Scholar] [CrossRef]
- Popova, N.K.; Amstislavskaya, T.G. Involvement of the 5-HT1A and 5-HT1B serotonergic receptor subtypes in sexual arousal in male mice. Psychoneuroendocrinology 2002, 27, 609–618. [Google Scholar] [CrossRef]
- Kathmann, M.; Flau, K.; Redmer, A.; Tränkle, C.; Schlicker, E. Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors. Naunyn. Schmiedebergs. Arch. Pharmacol. 2006, 372, 354–361. [Google Scholar] [CrossRef] [PubMed]
- Iuvone, T.; Esposito, G.; De Filippis, D.; Scuderi, C.; Steardo, L. Cannabidiol: A Promising Drug for Neurodegenerative Disorders? CNS Neurosci. Ther. 2009, 15, 65–75. [Google Scholar] [CrossRef]
- Jhaveri, M.D.; Sagar, D.R.; Elmes, S.J.R.; Kendall, D.A.; Chapman, V. Cannabinoid CB2 Receptor-Mediated Anti-nociception in Models of Acute and Chronic Pain. Mol. Neurobiol. 2007, 36, 26–35. [Google Scholar] [CrossRef]
- Rog, D.J.; Nurmikko, T.J.; Friede, T.; Young, C.A. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology 2005, 65, 812. [Google Scholar] [CrossRef]
- Chang, Y.-H.; Lee, S.T.; Lin, W.-W. Effects of cannabinoids on LPS-stimulated inflammatory mediator release from macrophages: Involvement of eicosanoids. J. Cell. Biochem. 2001, 81, 715–723. [Google Scholar] [CrossRef]
- Baldwin, G.C.; Tashkin, D.P.; Buckley, D.M.; Park, A.N.; Dubinett, S.M.; Roth, M.D. Marijuana and cocaine impair alveolar macrophage function and cytokane production. Am. J. Respir. Crit. Care Med. 1997, 156, 1606–1613. [Google Scholar] [CrossRef]
- Sido, J.M.; Nagarkatti, P.S.; Nagarkatti, M. Δ9-Tetrahydrocannabinol attenuates allogeneic host-versus-graft response and delays skin graft rejection through activation of cannabinoid receptor 1 and induction of myeloid-derived suppressor cells. J. Leukoc. Biol. 2015, 98, 435–447. [Google Scholar] [CrossRef]
- Lee, W.; Erdelyi, K.; Matyas, C.; Mukhopadhyay, P.; Varga, Z.V. Cannabidiol Limits T Cell – Mediated Chronic Autoimmune Myocarditis: Implications to Autoimmune Disorders and Organ Transplantation. Mol. Med. 2016, 22, 136–146. [Google Scholar] [CrossRef]
- Pandey, R.; Hegde, V.L.; Nagarkatti, M.; Nagarkatti, P.S.; Carolina, S. Targeting Cannabinoid Receptors as a Novel Approach in the Treatment of Graft-versus-Host Disease: Evidence from an Experimental Murine Model. J. Pharmacol. Exp. Ther. 2011, 338, 819–828. [Google Scholar] [CrossRef] [PubMed]
- Kozela, E.; Juknat, A.; Gao, F.; Kaushansky, N.; Coppola, G.; Vogel, Z. Pathways and gene networks mediating the regulatory effects of cannabidiol, a nonpsychoactive cannabinoid, in autoimmune T cells. J. Neuroinflammation 2016, 13, 1–19. [Google Scholar] [CrossRef] [PubMed]
- Rock, E.M.; Sullivan, M.T.; Pravato, S.; Pratt, M.; Limebeer, C.L.; Parker, L.A. Effect of combined doses of Δ(9)-tetrahydrocannabinol and cannabidiol or tetrahydrocannabinolic acid and cannabidiolic acid on acute nausea in male Sprague-Dawley rats. Psychopharmacology (Berl). 2020. [Google Scholar] [CrossRef] [PubMed]
- Id, A.J.; Gao, F.; Coppola, G.; Vogel, Z.; Kozela, E. miRNA expression profiles and molecular networks in resting and LPS-activated BV-2 microglia—Effect of cannabinoids. PLoS ONE 2019, 14, e0212039. [Google Scholar]
- Dumache, R.; Ciocan, V.; Muresan, C.; Rogobete, A.F.; Enache, A. Circulating microRNAs as promising biomarkers in forensic body fluids identification. Clin. Lab. 2015, 61, 1129–1135. [Google Scholar] [CrossRef]
- Dumache, R.; Rogobete, A.F.; Bedreag, O.H.; Sarandan, M.; Cradigati, A.C.; Papurica, M.; Dumbuleu, C.M.; Nartita, R.; Sandesc, D. Use of miRNAs as Biomarkers in Sepsis. Anal. Cell. Pathol. 2015, 2015, 186716. [Google Scholar] [CrossRef]
- Papurica, M.; Rogobete, A.F.; Sandesc, D.; Dumache, R.; Cradigati, C.A.; Sarandan, M.; Nartita, R.; Popovici, S.E.; Bedreag, O.H. Advances in Biomarkers in Critical Ill Polytrauma Patients. Clin. Lab. 2016, 62, 977–986. [Google Scholar] [CrossRef]
- Negoita, S.I.; Sandesc, D.; Rogobete, A.F.; Dutu, M.; Bedreag, O.H.; Papurica, M.; Ercisli, M.F.; Popovici, S.E.; Dumache, R.; Sandesc, M.; et al. MiRNAs expressions and interaction with biological systems in patients with Alzheimer’s disease. Using miRNAs as a diagnosis and prognosis biomarker. Clin. Lab. 2017, 63, 1315–1321. [Google Scholar] [CrossRef]
- Ivan, M.V.; Rogobete, A.F.; Bedreag, O.H.; Papurica, M.; Popovici, S.E.; Dinu, A.; Sandesc, M.; Beceanu, A.; Bratu, L.M.; Popoiu, C.M.; et al. New Molecular and Epigenetic Expressions as Novel Biomarkers in Critically Ill Polytrauma Patients with Acute Kidney Injury (AKI). Clin. Lab. 2018, 64, 663–668. [Google Scholar] [CrossRef]
- Koukos, G.; Polytarchou, C.; Kaplan, J.L.; Morley-Fletcher, A.; Gras-Miralles, B.; Kokkotou, E.; Baril-Dore, M.; Pothoulakis, C.; Winter, H.S.; Iliopoulos, D. MicroRNA-124 regulates STAT3 expression and is down-regulated in colon tissues of pediatric patients with ulcerative colitis. Gastroenterology 2013, 145, 842–852. [Google Scholar] [CrossRef]
- Ma, C.; Li, Y.; Li, M.; Deng, G.; Wu, X.; Zeng, J.; Hao, X.; Wang, X.; Liu, J.; Cho, W.C.S.; et al. microRNA-124 negatively regulates TLR signaling in alveolar macrophages in response to mycobacterial infection. Mol. Immunol. 2014, 62, 150–158. [Google Scholar] [CrossRef] [PubMed]
- Dasgupta, N.; Peng, Y.; Tan, Z.; Ciraolo, G.; Wang, D.; Li, R. miRNAs in mtDNA-less cell mitochondria. Cell Death Discov. 2015, 1, 1–6. [Google Scholar] [CrossRef] [PubMed]
- Wang, H.; Li, J.; Chi, H.; Zhang, F.; Zhu, X. MicroRNA-181c targets Bcl-2 and regulates mitochondrial morphology in myocardial cells. 2015, 19, 2084–2097. J. Cell. Mol. Med. 2015, 19, 20. [Google Scholar] [CrossRef] [PubMed]
- Sun, X.; Icli, B.; Wara, A.K.; Belkin, N.; He, S.; Kobzik, L.; Hunninghake, G.M.; Vera, M.P.; Registry, M.; Blackwell, T.S.; et al. MicroRNA-181b regulates NF- κ B – mediated vascular inflammation. J. Clin. Investig. 2012, 122, 1973–1990. [Google Scholar] [CrossRef]
- Mu, N.; Gu, J.; Huang, T.; Zhang, C.; Shu, Z.; Li, M.; Hao, Q.; Li, W.; Zhang, W.; Zhao, J.; et al. A novel NF-κB/YY1/microRNA-10a regulatory circuit in fibroblast-like synoviocytes regulates inflammation in rheumatoid arthritis. Sci. Rep. 2016, 6, 20059. [Google Scholar] [CrossRef]
- Jeker, L.T.; Zhou, X.; Gershberg, K.; De Kouchkovsky, D.; Morar, M.M.; Stadthagen, G.; Lund, A.H.; Bluestone, J.A.
- Sheedy, F.J.; Palsson-McDermott, E.; Hennessy, E.J.; Martin, C.; O’Leary, J.J.; Ruan, Q.; Johnson, D.S.; Chen, Y.; O’Neill, L.A.J. Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nat. Immunol. 2010, 11, 141–147. [Google Scholar] [CrossRef]
- Liu, S.S.; Wang, Y.U.S.H.I.; Sun, Y.A.N.F.; Miao, L.I.X.I.A. Plasma microRNA - 320, microRNA - let - 7e and microRNA - 21 as novel potential biomarkers for the detection of retinoblastoma. Biomedical Reports 2014, 424–428. [Google Scholar] [CrossRef]
- Lin, Q.; Geng, Y.; Zhao, M.; Lin, S.; Zhu, Q.; Tian, Z. MiR-21 Regulates TNF-alpha-Induced CD40 Expression via the SIRT1-NF-kappaB Pathway in Renal Inner Medullary Collecting Duct Cells. Cell. Physiol. Biochem. 2017, 41, 124–136. [Google Scholar] [CrossRef]
- Canfran-Duque, A.; Rotllan, N.; Zhang, X.; Fernandez-Fuertes, M.; Ramirez-Hidalgo, C.; Araldi, E.; Daimiel, L.; Busto, R.; Fernandez-Hernando, C.; Suarez, Y. Macrophage deficiency of miR-21 promotes apoptosis, plaque necrosis, and vascular inflammation during atherogenesis. EMBO Mol. Med. 2017, 9, 1244–1262. [Google Scholar] [CrossRef]
- Caescu, C.I.; Guo, X.; Tesfa, L.; Bhagat, T.D.; Verma, A.; Zheng, D.; Stanley, E.R. Colony stimulating factor-1 receptor signaling networks inhibit mouse macrophage inflammatory responses by induction of microRNA-21. Blood 2015, 125, e1–e13. [Google Scholar] [CrossRef] [PubMed]
- Das, A.; Ganesh, K.; Khanna, S.; Sen, C.K.; Roy, S. Engulfment of apoptotic cells by macrophages: A role of microRNA-21 in the resolution of wound inflammation. J. Immunol. 2014, 192, 1120–1129. [Google Scholar] [CrossRef] [PubMed]
- Cd, H.S.-; Cells, S.-C.D.; Wu, Q.; Zhan, J.; Li, Y.; Wang, X.; Xu, L.; Yu, J.; Pu, S.; Zhou, Z. Differentiation-Associated MicroRNA Alterations in Mouse. Stem cells International 2016, 2016. [Google Scholar]
- Suarez, Y.; Wang, C.; Manes, T.D.; Pober, J.S. Cutting edge: TNF-induced microRNAs regulate TNF-induced expression of E-selectin and intercellular adhesion molecule-1 on human endothelial cells: Feedback control of inflammation. J. Immunol. 2010, 184, 21–25. [Google Scholar] [CrossRef]
- Ganan-Gomez, I.; Wei, Y.; Yang, H.; Pierce, S.; Bueso-Ramos, C.; Calin, G.; Boyano-Adanez, M.D.C.; Garcia-Manero, G. Overexpression of miR-125a in myelodysplastic syndrome CD34+ cells modulates NF-kappaB activation and enhances erythroid differentiation arrest. PLoS ONE 2014, 9, e93404. [Google Scholar] [CrossRef]
- Ho, J.; Chan, H.; Wong, S.H.; Wang, M.H.T.; Yu, J.; Xiao, Z.; Liu, X.; Choi, G.; Leung, C.C.H.; Wong, W.T.; et al. The involvement of regulatory non-coding RNAs in sepsis: A systematic review. Crit. Care 2016, 20, 1–12. [Google Scholar] [CrossRef]
- Gaston, T.E.; Friedman, D. Pharmacology of cannabinoids in the treatment of epilepsy. Epilepsy. Behav. 2017, 70, 313–318. [Google Scholar] [CrossRef]
- O’Neill, L.A.J.; Bowie, A.G. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat. Rev. Immunol. 2007, 7, 353–364. [Google Scholar] [CrossRef]
- Chen, X.-M.; Splinter, P.L.; O’Hara, S.P.; LaRusso, N.F. A cellular micro-RNA, let-7i, regulates Toll-like receptor 4 expression and contributes to cholangiocyte immune responses against Cryptosporidium parvum infection. J. Biol. Chem. 2007, 282, 28929–28938. [Google Scholar] [CrossRef]
- Ma, C.; Li, Y.; Zeng, J.; Wu, X.; Liu, X.; Wang, Y. Mycobacterium bovis BCG Triggered MyD88 Induces miR-124 Feedback Negatively Regulates Immune Response in Alveolar Epithelial Cells. PLoS ONE 2014, 9, e92419. [Google Scholar] [CrossRef]
- Liang, H.; Yan, X.; Pan, Y.; Wang, Y.; Wang, N.; Li, L.; Liu, Y.; Chen, X. MicroRNA-223 delivered by platelet-derived microvesicles promotes lung cancer cell invasion via targeting tumor suppressor EPB41L3. Mol. Cancer 2015, 14, 58. [Google Scholar] [CrossRef] [PubMed]
- Qi, J.; Qiao, Y.; Wang, P.; Li, S.; Zhao, W.; Gao, C. microRNA-210 negatively regulates LPS-induced production of proinflammatory cytokines by targeting NF-kappaB1 in murine macrophages. FEBS Lett. 2012, 586, 1201–1207. [Google Scholar] [CrossRef] [PubMed]
- Meng, Q.-T.; Chen, R.; Chen, C.; Su, K.; Li, W.; Tang, L.-H.; Liu, H.-M.; Xue, R.; Sun, Q.; Leng, Y.; et al. Transcription factors Nrf2 and NF-κB contribute to inflammation and apoptosis induced by intestinal ischemia-reperfusion in mice. Int. J. Mol. Med. 2017, 40, 1731–1740. [Google Scholar] [CrossRef] [PubMed]
- Xiao, B.; Liu, Z.; Li, B.-S.; Tang, B.; Li, W.; Guo, G.; Shi, Y.; Wang, F.; Wu, Y.; Tong, W.-D.; et al. Induction of microRNA-155 during Helicobacter pylori infection and its negative regulatory role in the inflammatory response. J. Infect. Dis. 2009, 200, 916–925. [Google Scholar] [CrossRef] [PubMed]
- Wu, M.; Gu, J.T.; Yi, B.I.N.; Tang, Z.Z.H.I.; Tao, G.U. microRNA-23b regulates the expression of inflammatory factors in vascular endothelial cells during sepsis. Exp. Ther. Med. 2015, 9, 1125–1132. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Dalli, J.; Chiang, N.; Baron, R.M.; Quintana, C.; Serhan, C.N. Article Plasticity of Leukocytic Exudates in Resolving Acute Inflammation Is Regulated by MicroRNA and Proresolving Mediators. Immunity 2013, 39, 885–898. [Google Scholar] [CrossRef]
- Ma, X.; Buscaglia, L.E.B.; Barker, J.R.; Li, Y. MicroRNAs in NF-kB signaling. J. Mol. Cell Biol. 2011, 3, 159–166. [Google Scholar] [CrossRef]
- Yang, X.; Bam, M.; Nagarkatti, P.S.; Nagarkatti, M. RNA-seq Analysis of δ9-Tetrahydrocannabinol-treated T Cells Reveals Altered Gene Expression Profiles That Regulate Immune Response and Cell Proliferation. J. Biol. Chem. 2016, 291, 15460–15472. [Google Scholar] [CrossRef]
- Rao, R.; Nagarkatti, P.S.; Nagarkatti, M. Δ9 Tetrahydrocannabinol attenuates Staphylococcal enterotoxin B-induced inflammatory lung injury and prevents mortality in mice by modulation of miR-17-92 cluster and induction of T-regulatory cells Tables of Links. Br. J. Pharmacol. 2015, 172, 1792–1806. [Google Scholar] [CrossRef]
- Ingram, G.; Pearson, O.R. Cannabis and multiple sclerosis. Pract Neurol. 2019, 19, 310–315. [Google Scholar] [CrossRef]
- Sripada, L.; Tomar, D.; Singh, R. Mitochondrion Mitochondria: One of the destinations of miRNAs. MITOCH 2012, 12, 593–599. [Google Scholar] [CrossRef] [PubMed]
- Kren, B.T.; Wong, P.Y.; Sarver, A.; Zhang, X.; Zeng, Y.; Steer, C.J. MicroRNAs identified in highly purified liver-derived mitochondria may play a role in apoptosis. RNA Biol. 2009, 6, 65–72. [Google Scholar] [CrossRef] [PubMed]
- Sripada, L.; Tomar, D.; Prajapati, P.; Singh, R.; Singh, A.K.; Singh, R. Systematic Analysis of Small RNAs Associated with Human Mitochondria by Deep Sequencing: Detailed Analysis of Mitochondrial Associated miRNA. PLoS ONE 2012, 7, e44873. [Google Scholar] [CrossRef] [PubMed]
- Bian, H.; Peng, X.; Huang, F.; Yao, D.; Yu, Q.; Liang, H. The Spectroscopy Study of the Binding of an Active Ingredient of Dioscorea Species with Bovine Serum Albumin with or without Co 2+. Evid. Based Complementary Altern. Med. 2014. [Google Scholar] [CrossRef]
- Zhou, W.; Su, L.; Duan, X.; Chen, X.; Hays, A.; Upadhyayula, S.; Shivde, J.; Wang, H.; Li, Y.; Huang, D.; et al. MicroRNA-21 down-regulates inflammation and inhibits periodontitis. Mol. Immunol. 2018, 101, 608–614. [Google Scholar] [CrossRef]
- Sido, J.M.; Jackson, A.R.; Nagarkatti, P.S.; Nagarkatti, M. Marijuana-derived Δ-9-tetrahydrocannabinol suppresses Th1/Th17 cell-mediated delayed-type hypersensitivity through microRNA regulation. J. Mol. Med. 2016, 94, 1039–1051. [Google Scholar] [CrossRef]
- Al-Ghezi, Z.Z.; Miranda, K.; Nagarkatti, M.; Nagarkatti, P.S. Combination of Cannabinoids, Δ9- Tetrahydrocannabinol and Cannabidiol, Ameliorates Experimental Multiple Sclerosis by Suppressing Neuroinflammation Through Regulation of miRNA-Mediated Signaling Pathways. Front. Immunol. 2019, 10, 1–17. [Google Scholar] [CrossRef]
- Lehmann, C.; Kianian, M.; Zhou, J.; Küster, I.; Kuschnereit, R.; Whynot, S.; Hung, O.; Shukla, R.; Johnston, B.; Cerny, V.; et al. Cannabinoid receptor 2 activation reduces intestinal leukocyte recruitment and systemic inflammatory mediator release in acute experimental sepsis. Crit. Care 2012, 16. [Google Scholar] [CrossRef]
- Çakır, M.; Tekin, S.; Okan, A.; Çakan, P.; Doğanyiğit, Z. The ameliorating effect of cannabinoid type 2 receptor activation on brain, lung, liver and heart damage in cecal ligation and puncture-induced sepsis model in rats. Int. Immunopharmacol. 2019, 78. [Google Scholar] [CrossRef]
- Newton, C.A.; Klein, T.W.; Friedman, H. Secondary immunity to Legionella pneumophila and Th1 activity are suppressed by delta-9-tetrahydrocannabinol injection. Infect. Immun. 1994, 62, 4015–4020. [Google Scholar] [CrossRef]
- Gardner, B.; Zu, L.X.; Sharma, S.; Liu, Q.; Makriyannis, A.; Tashkin, D.P.; Dubinett, S.M. Autocrine and Paracrine Regulation of Lymphocyte CB2 Receptor Expression by TGF-β. Biochem. Biophys. Res. Commun. 2002, 290, 91–96. [Google Scholar] [CrossRef] [PubMed]
- Croxford, J.L.; Yamamura, T. Cannabinoids and the immune system: Potential for the treatment of inflammatory diseases? J. Neuroimmunol. 2005, 166, 3–18. [Google Scholar] [CrossRef] [PubMed]
- Mageed, R.A.; Adams, G.; Woodrow, D.; Podhajcer, O.L.; Chernajovsky, Y. Prevention of collagen-induced arthritis by gene delivery of soluble p75 tumour necrosis factor receptor. Gene Ther. 1998, 5, 1584–1592. [Google Scholar] [CrossRef] [PubMed]
- Triantaphyllopoulos, K.A.; Williams, R.O.; Tailor, H.; Chernajovsky, Y. Amelioration of collagen-induced arthritis and suppression of interferon-γ, interleukin-12, and tumor necrosis factor α production by interferon-β gene therapy. Arthritis Rheum. 1999, 42, 90–99. [Google Scholar] [CrossRef]
- David, V.L.; Izvernariu, D.A.; Popoiu, C.M.; Puiu, M.; Boia, E.S. Morphologic, morphometrical and histochemical proprieties of the costal cartilage in children with pectus excavatum. Rom. J. Morphol. Embryol. 2011, 52, 625–629. [Google Scholar]
- Ross, R.A.; Brockie, H.C.; Pertwee, R.G. Inhibition of nitric oxide production in RAW264.7 macrophages by cannabinoids and palmitoylethanolamide. Eur. J. Pharmacol. 2000, 401, 121–130. [Google Scholar] [CrossRef]
- Watzl, B.; Scuderi, P.; Watson, R.R. marijuana components stimulate human peripheral bloodmonon uclear cell secretion of interferon - gammaandsuppress interleukin-1 alpha in vitro. Int. J. Immunopharmacol. 1991, 13, 1091–1097. [Google Scholar] [CrossRef]
- Srivastava, M.D.; Srivastava, B.I.S.; Brouhard, B. Δ9 Tetrahydrocannabinol and cannabidiol alter cytokine production by human immune cells. Immunopharmacology 1998, 40, 179–185. [Google Scholar] [CrossRef]
- Yuan, M.; Kiertscher, S.M.; Cheng, Q.; Zoumalan, R.; Tashkin, D.P.; Roth, M.D. Δ9-Tetrahydrocannabinol regulates Th1/Th2 cytokine balance in activated human T cells. J. Neuroimmunol. 2002, 133, 124–131. [Google Scholar] [CrossRef]
- Aziz, M.; Jacob, A.; Yang, W.-L.; Matsuda, A.; Wang, P. Current trends in inflammatory and immunomodulatory mediators in sepsis. J. Leukoc. Biol. 2013, 93, 329–342. [Google Scholar] [CrossRef]



Disorder | Observations | Reference |
---|---|---|
Pain | CB1 receptor agonists have a nociceptive action on the interneurons in the spinal cord, CB2 acts directly on reducing inflammation, and the CB2 receptor was shown to have an increased immunomodulatory response. | [63] |
Cancer | The following effects have been reported: Anti-inflammatory, anti-proliferative, pro-apoptotic, anti-invasive, and anti-metastatic. | [50,51,64] |
Hepatic metabolism | Directly acts on the modulation of the hepatic metabolism through gluconeogenesis and lipogenesis, and the CB2 receptor has a protective action on the phenomenon induced by ischemia reperfusion injury. | [47,49,65,66,67] |
Gastrointestinal system | CB1 and CB2 receptors inhibit the pro-inflammatory and pro-oxidative activities specifically for the colon. | [49,65,68] |
Cardiovascular system | CB2 receptor reduces inflammation specifically related to atheromatous plaques and reduces thrombosis risk; CB1 activates AMP-activated protein kinase (AMPK), reduces insulin resistance, and mimics all of the effects that encompass ischemia-reperfusion injury (IR). | [40,68,69,70] |
Immune system/inflammation response | Reduces iNOS activity, reduces IL-6 expression; reduces TNF-α and IL-1β expression; reduces specific inflammation of ARDS/ALI; modulates and reduces the activity of TNF-α and COX-2 in the context of LPS-induced inflammation; inhibits neutrophil chemotaxis; and modulates the expression of IFN-γ, leading to the decrease of IL-2 expression. | [53,71,72,73,74,75] |
Cannabinoid | Observations | References |
---|---|---|
CBD in vitro and in vivo studies |
| [108,109,110,111,112,113,114,115,116,117,118,119,120,121,122] |
THC in vivo and in vitro studies |
| [105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123] |
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