hole liver only flows to the remaining 1/3 from the liver tissue (36). A basic mathematical deduction demonstrates that this can inevitably bring about two results: first, the friction exerted by blood flow on the endothelial surface increases significantly, that is, there is certainly a rise in shear strain (37,38); second, every liver cell getting quite a few signal things from the portal vein is several instances that prior to liver resection. The hepatic-portal shunt model was established to maintain the blood stress constant and stable just after PHx. Prior findings indicate that the liver could not regenerate in time, which confirm the vital role of portal blood pressure changes for liver injury perception and growth signal activation (39). Research have identified that hemodynamic changes within the portal vein cause increased shear pressure in liver sinusoidal endothelial cells (LSECs), which in turn promotes the release of nitric oxide (NO), which increases the sensitivity of hepatocytes to hepatocyte growth issue (HGF) (40), induces vascular endothelial development aspect (VEGF) (41,42), and stimulates HSCs to release HGF and VEGF (43). The interleukin (IL)-6 released by LSEC may also lead to a rise in shear tension. Compared with unstretched LSECs, mechanically stretched LSECs releases much more IL-6 (44). Correspondingly, an improvement in shear pressure will increase the activity of urokinase-type plasminogen IRAK4 Storage & Stability activator (uPA) (45,46). The fast activation of uPA causes the conversion of plasminogen to plasmin, which subsequently initiates breakdown of extracellular matrix (ECM) constituents and cuts precursor (pro-HGF) molecules into active HGF binding to hepatocyte development element receptor (HGFR or c-Met) (47-50). EGF increases in relative concentration as a result of raise in portal venous flow and motivates the epidermal growth element receptor (EGFR, also referred to as ErbB) (51,52). Activated HGFR and EGFR trigger the liver regeneration cascade, like phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinases (MAPK, also known as Ras/Raf/MEK/Erk), and elevate the enhanced expression of c-myc, c-fos, c-jun, and also other transcription aspects, which ultimately facilitates protein CDK12 medchemexpress synthesis and cell division (40). Innate immune response The innate immune response is also regarded as a significant stimulus of liver regeneration (53,54). As elements of innate immunity, lipopolysaccharide (LPS) and complements (for instance C3a and C5a) are released in the intestinal tractAnn Transl Med 2021;9(22):1705 | dx.doi.org/10.21037/atm-21-Annals of Translational Medicine, Vol 9, No 22 November 2021 Table 1 The potential mechanisms via which PHx could trigger liver regeneration Trigger Elevation of shear tension Elevation of shear anxiety Elevation of shear stress Elevation of shear stress Innate immune response Innate immune response Innate immune response Hemostasis activation Hemostasis activation Animal Rat Rat Mice Degree of PHx Effect MechanismPage five ofRef (38) (40) (42)2/3PHx Initiates and maintains liver regeneration 2/3PHx Triggers the liver regeneration cascade 2/3PHx The decreased serum nitrate and nitrite levels cause decrease liver mass recovery and higher ALT 2/3PHx Initiates liver regenerationProper portal blood perfusion; Hepatocyte membrane and sodium-potassium pump modifications Expression of c-fos mRNA; Release of NO and proliferation aspects Release of NO; The HSP70 family and Ki-67; Induction of Nrp1 and EGFR uPA and uPAR activat