hole liver only flows towards the remaining 1/3 from the liver tissue (36). A basic mathematical deduction demonstrates that this can inevitably result in two outcomes: first, the friction exerted by blood flow around the endothelial surface increases considerably, that may be, there is an increase in shear strain (37,38); second, every liver cell receiving a number of signal variables from the portal vein is numerous times that just before liver resection. The hepatic-portal shunt model was established to help keep the blood stress continuous and steady just after PHx. Preceding findings indicate that the liver could not regenerate in time, which confirm the essential function of portal blood stress alterations for liver injury perception and growth signal activation (39). Studies have found that hemodynamic alterations in the portal vein result in enhanced shear stress 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 growth element (VEGF) (41,42), and stimulates HSCs to release HGF and VEGF (43). The interleukin (IL)-6 released by LSEC may possibly also bring about a rise in shear anxiety. Compared with unstretched LSECs, mechanically stretched LSECs releases much more IL-6 (44). Correspondingly, an improvement in shear anxiety will increase the activity of urokinase-type plasminogen activator (uPA) (45,46). The rapid 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 growth element receptor (HGFR or c-Met) (47-50). EGF increases in relative concentration because of the enhance in portal venous flow and motivates the epidermal HDAC10 site development factor receptor (EGFR, also known as ErbB) (51,52). Activated HGFR and EGFR trigger the liver regeneration cascade, including phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinases (MAPK, also called Ras/Raf/MEK/Erk), and elevate the enhanced expression of c-myc, c-fos, c-jun, along with other transcription variables, which ultimately facilitates protein 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 (such as C3a and C5a) are released from 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 prospective mechanisms via which PHx might trigger liver regeneration Trigger Elevation of shear pressure Elevation of shear stress Elevation of shear stress Elevation of shear pressure 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 KDM2 Formulation nitrite levels result in reduce liver mass recovery and larger 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 components Release of NO; The HSP70 loved ones and Ki-67; Induction of Nrp1 and EGFR uPA and uPAR activat