Another modern topic involves deciphering transitional evolutiona

Another modern topic involves deciphering transitional evolutionary conditions. For plants, PCM and other evidence indicate that evolutionary transitions to dioecy from cosexuality often occur along an evolutionary pathway that entails gynodioecy as an intermediate stage. For invertebrate animals, however, intermediate evolutionary buy HM781-36B states generally have been harder to identify, in part because androdioecy and gynodioecy are rare and probably transient

conditions in animals. Perhaps contrary to naive expectations, sexual selection (selective pressures arising from competition for mates or for opposite-sex gametes) does not cease with the evolutionary dissolution of the separate-sex condition. Instead, evidence of many sorts strongly implicates continuing pervasive roles for sexual selection in the evolution of sex-related phenotypes in hermaphroditic animals (Leonard, 2006) and dual-sex plants

(Willson, 1990). Dual sexuality opens a window of opportunity for self-fertilization that simply is closed to gonochoristic or dioecious species. But this option may or may not be exercised depending on the species and circumstance. For example, many hermaphroditic plant species have evolved mechanisms such as dichogamy (a temporal separation Akt inhibitor in an individual’s production of male and female gametes), herkogamy (a physical separation of male and female gametes Evodiamine on a plant), and genetic self-incompatibilities, all of which can inhibit selfing, promote outcrossing, and thereby circumvent inbreeding depression. These mechanisms

often are less than fully effective, however, with the net result that many dual-sex plant species display ‘mixed-mating’ systems with intermediate rates of selfing and outcrossing, and the same holds true for many invertebrate animals (Jarne & Auld, 2006). Species that show gynodioecy or androdioecy (or other categories of dual sexuality) also can have mixed-mating systems. The outcrossing component is guaranteed (assuming that pure males and pure females are reproductively successful), so the behavior of hermaphroditic specimens determines whether selfing (and hence mixed-mating) applies as well. At least one vertebrate species – the mangrove killifish (K. marmoratus) – also shows a mixed-mating system of selfing and outcrossing (Mackiewicz et al., 2006b). Some populations of this species include functional adult males as well as the hermaphrodites with whom the males apparently outcross occasionally (Mackiewicz et al., 2006a-2006c). Thus, mixed-mating systems have evolved convergently not only in numerous plants and invertebrate animals but also in this one small vertebrate clade (Tatarenkov et al., 2009). In the case of K.

Another modern topic involves deciphering transitional evolutiona

Another modern topic involves deciphering transitional evolutionary conditions. For plants, PCM and other evidence indicate that evolutionary transitions to dioecy from cosexuality often occur along an evolutionary pathway that entails gynodioecy as an intermediate stage. For invertebrate animals, however, intermediate evolutionary buy Tamoxifen states generally have been harder to identify, in part because androdioecy and gynodioecy are rare and probably transient

conditions in animals. Perhaps contrary to naive expectations, sexual selection (selective pressures arising from competition for mates or for opposite-sex gametes) does not cease with the evolutionary dissolution of the separate-sex condition. Instead, evidence of many sorts strongly implicates continuing pervasive roles for sexual selection in the evolution of sex-related phenotypes in hermaphroditic animals (Leonard, 2006) and dual-sex plants

(Willson, 1990). Dual sexuality opens a window of opportunity for self-fertilization that simply is closed to gonochoristic or dioecious species. But this option may or may not be exercised depending on the species and circumstance. For example, many hermaphroditic plant species have evolved mechanisms such as dichogamy (a temporal separation see more in an individual’s production of male and female gametes), herkogamy (a physical separation of male and female gametes ioxilan on a plant), and genetic self-incompatibilities, all of which can inhibit selfing, promote outcrossing, and thereby circumvent inbreeding depression. These mechanisms

often are less than fully effective, however, with the net result that many dual-sex plant species display ‘mixed-mating’ systems with intermediate rates of selfing and outcrossing, and the same holds true for many invertebrate animals (Jarne & Auld, 2006). Species that show gynodioecy or androdioecy (or other categories of dual sexuality) also can have mixed-mating systems. The outcrossing component is guaranteed (assuming that pure males and pure females are reproductively successful), so the behavior of hermaphroditic specimens determines whether selfing (and hence mixed-mating) applies as well. At least one vertebrate species – the mangrove killifish (K. marmoratus) – also shows a mixed-mating system of selfing and outcrossing (Mackiewicz et al., 2006b). Some populations of this species include functional adult males as well as the hermaphrodites with whom the males apparently outcross occasionally (Mackiewicz et al., 2006a-2006c). Thus, mixed-mating systems have evolved convergently not only in numerous plants and invertebrate animals but also in this one small vertebrate clade (Tatarenkov et al., 2009). In the case of K.

3–10%, it follows that about 2400–4800 patients suffer adverse e

3–1.0%, it follows that about 2400–4800 patients suffer adverse events and up to 480 die every year directly as a result of ERCP. The Joint Advisory Group FK506 datasheet on GI endoscopy of the United Kingdom has recommended a minimum of two ERCP-trained endoscopists within a centre or local network to enable continuous service provision. ERCP endoscopists who wish to continue to partake in the ERCP service should currently aim to achieve a minimum of 75 cases per year. The aim of the study is to describe the practice of single handed low volume ERCP in a district general hospital in England with particular emphasis on the success rates of the technical aspects of the procedures and the rates of complications.

Methods: Descriptive study with prospective data collection from 500 patients undergoing ERCP between 2006 and 2012. The main outcomes were technical success (cannulation rates and therapeutic success rates) and safety (complication rate). Results: Technical success rates

were high: cannulation of common bile duct was achieved in 90% during 2006–2012; high success rates were also achieved for sphincterotomy, pre-cut incision, selleck stent insertion and stone removal. The complication rate was low: post ERCP pancreatitis accured in 6%, decreasing to 1% during 2009–2012; no procedure related perforation, haemorrhage and mortality. During the study period, the success rates for cannulation and therapeutic procedures increased, while complications decreased Conclusion: The diagnostic

and therapeutic success rates by strict intention to treat analysis were excellent while the risk of complications was low. The low risk of complications draw attention to the changes that have taken place over the past decade particularly in relation to the selection of most suitable patients for the procedure. mafosfamide Key Word(s): 1. ERCP; 2. LOW VOLUME ERCP; Presenting Author: HUI XU Additional Authors: JING YU Corresponding Author: HUI XU Affiliations: General Hospital of Chengdu Military Region Objective: To probe Capsule endoscopy used in digestivetract hemorrhageof undetermined origin examination preoperative preparation method, then try to find an ideal preoperative method which increases the detection rate of diseases. Methods: From 2009 July to 2012 June, a result of treatment of hemorrhage of digestive tract, 62 cases of patients with gastrointestinal endoscopy is not clear diagnosis, were randomly divided into 3 groups. 19 cases in group A (compound polyethylene glycol electrolyte powder), 21 cases in B group (A group based on the combined with dimethicone powder), 22 cases in C group (B group based on the combination of Mosapride Citrate Dispersible Tablets). Observation of capsule endoscopy through the pylorus intestine examination time, completion rate, quality of image acquisition (bubble volume, digestive fluid volume, digestive fluid cleanliness and overall observation effect), lesion detection, safety of capsule endoscopy in preoperative bowel preparation, and so on.

3–10%, it follows that about 2400–4800 patients suffer adverse e

3–1.0%, it follows that about 2400–4800 patients suffer adverse events and up to 480 die every year directly as a result of ERCP. The Joint Advisory Group http://www.selleckchem.com/products/GDC-0941.html on GI endoscopy of the United Kingdom has recommended a minimum of two ERCP-trained endoscopists within a centre or local network to enable continuous service provision. ERCP endoscopists who wish to continue to partake in the ERCP service should currently aim to achieve a minimum of 75 cases per year. The aim of the study is to describe the practice of single handed low volume ERCP in a district general hospital in England with particular emphasis on the success rates of the technical aspects of the procedures and the rates of complications.

Methods: Descriptive study with prospective data collection from 500 patients undergoing ERCP between 2006 and 2012. The main outcomes were technical success (cannulation rates and therapeutic success rates) and safety (complication rate). Results: Technical success rates

were high: cannulation of common bile duct was achieved in 90% during 2006–2012; high success rates were also achieved for sphincterotomy, pre-cut incision, find more stent insertion and stone removal. The complication rate was low: post ERCP pancreatitis accured in 6%, decreasing to 1% during 2009–2012; no procedure related perforation, haemorrhage and mortality. During the study period, the success rates for cannulation and therapeutic procedures increased, while complications decreased Conclusion: The diagnostic

and therapeutic success rates by strict intention to treat analysis were excellent while the risk of complications was low. The low risk of complications draw attention to the changes that have taken place over the past decade particularly in relation to the selection of most suitable patients for the procedure. Cetuximab chemical structure Key Word(s): 1. ERCP; 2. LOW VOLUME ERCP; Presenting Author: HUI XU Additional Authors: JING YU Corresponding Author: HUI XU Affiliations: General Hospital of Chengdu Military Region Objective: To probe Capsule endoscopy used in digestivetract hemorrhageof undetermined origin examination preoperative preparation method, then try to find an ideal preoperative method which increases the detection rate of diseases. Methods: From 2009 July to 2012 June, a result of treatment of hemorrhage of digestive tract, 62 cases of patients with gastrointestinal endoscopy is not clear diagnosis, were randomly divided into 3 groups. 19 cases in group A (compound polyethylene glycol electrolyte powder), 21 cases in B group (A group based on the combined with dimethicone powder), 22 cases in C group (B group based on the combination of Mosapride Citrate Dispersible Tablets). Observation of capsule endoscopy through the pylorus intestine examination time, completion rate, quality of image acquisition (bubble volume, digestive fluid volume, digestive fluid cleanliness and overall observation effect), lesion detection, safety of capsule endoscopy in preoperative bowel preparation, and so on.

Previously, we reported that short-term ingestion of DDC diet by

Previously, we reported that short-term ingestion of DDC diet by hepatocyte-specific β-catenin conditional knockout (KO) mice led to fewer A6-positive oval cells than wildtype (WT) littermates. To examine the role of β-catenin in chronic hepatic injury and repair, we exposed WT and KO mice to DDC for 80 and 150 days. Paradoxically, long-term DDC exposure led to significantly more A6-positive cells, indicating greater atypical ductular proliferation in KO, which coincided with increased fibrosis and cholestasis. Surprisingly, at 80 and 150 days in KO we observed a significant amelioration of hepatocyte injury. This coincided with extensive repopulation of β-catenin

null livers with β-catenin-positive hepatocytes at 150 days, which was preceded by appearance of β-catenin-positive hepatocyte clusters at 80 days and a few β-catenin-positive hepatocytes at earlier times. Intriguingly, occasional β-catenin-positive TSA HDAC in vitro hepatocytes that were negative for progenitor markers were also observed at baseline in the KO livers, suggesting spontaneous escape from cre-mediated recombination. These cells with hepatocyte morphology expressed mature hepatocyte markers but lacked markers of hepatic progenitors. The gradual PLX4032 in vivo repopulation of KO livers with β-catenin-positive hepatocytes occurred only following DDC injury and coincided with a progressive loss of hepatic cre-recombinase

expression. A few β-catenin-positive cholangiocytes were observed albeit only after long-term DDC exposure and trailed the appearance of β-catenin-positive hepatocytes. Conclusion: In PIK3C2G a chronic liver injury model, β-catenin-positive hepatocytes exhibit growth and survival advantages and repopulate KO livers, eventually limiting hepatic

injury and dysfunction despite increased fibrosis and intrahepatic cholestasis. (HEPATOLOGY 2011;) Expansion of hepatic progenitors in the liver has been observed in chronic liver injury and is believed to me a mode of repair. One model currently used in mouse that induces chronic liver injury and oval cell activation is the exposure to a diet containing 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). This induces atypical ductular proliferation along with periportal inflammation and plugging of the bile ducts with porphyrin crystallization.1 Ultimately, injury to the biliary epithelium and clogging of the ducts induces biliary stasis and a subsequent rise in serum bilirubin. It is believed that hepatic oval cells arise as a response to the hepatobiliary injury in this model. A more recent study presented long-term feeding of DDC as a model of xenobiotic-induced cholangiopathy representative of sclerosing cholangitis and biliary cirrhosis.2 Various molecular pathways have been implicated in the oval cell response.

3; CI 15–35) and a previous child with haemophilia (RR 22; CI

3; CI 1.5–3.5) and a previous child with haemophilia (RR 2.2; CI 1.4–3.4). More than half of all Dutch haemophilia carriers underwent prenatal diagnosis. Several determinants were strongly associated see more with prenatal diagnosis. “
“Summary.  Sport is increasingly recommended for haemophilic patients due to physical and psychological benefits. ‘WATERCISE’ is a specific aqua-training programme for

haemophiliacs in which endurance, strength, coordination and mobility are trained. In the WAT-QoL study benefits and risks of regular WATERCISE training sessions were investigated in terms of health-related quality of life (HRQoL), physical functioning (PF), orthopaedic joint status (OJS), bleeding frequency and factor consumption. Patients in the WATERCISE group attended an aqua-training

programme once a week for 1 h over 12 months, patients in the control group did not. Patients were matched for clinical and demographic data. Information on clinical data, orthopaedic status, PF (HEP-Test-Q) and HRQoL were collected in both groups at baseline and at follow-up (6 and 12 months). Twenty-eight adult severely affected haemophilic patients (WATERCISE group: 10 haemophilia A (HA), 3 haemophilia B (HB) patients; control group: 12 HA and 3 HB patients) were enrolled (aged 40.68 ± 12.7 years). Baseline data (body mass indices, OJS, sportive activities, HRQoL and PF) were well distributed between groups. Selleck Deforolimus After 12 months the WATERCISE group reported a significantly better PF (MW = 65.22, SD = 11.3; MC = 52.5, SD = 15.0), especially for endurance (P < 0.004). Although always differently reported by the patients within the WATERCISE

group, HRQoL did not prove to be significantly different between groups. WATERCISE seems to Montelukast Sodium have a positive effect on the PF of patients suffering from haemophilia. These study findings need to be further investigated in a larger study group. “
“Summary.  While the majority of this session will deal with selected inherited vascular abnormalities that may manifest as a haemorrhagic disorder, the initial discussion by Dr Key will focus on the interplay between the vessel wall and components of the coagulation system, with a focus on haemophilia A and B. Although it is generally accepted that physiological haemostasis is triggered by contact of blood with tissue factor (TF), there remains some controversy regarding the cellular origin of TF in vivo. In addition, the initiation and propagation of thrombin generation are highly dependent on the balance of pro- and anticoagulant functions of endothelium, a profile that varies significantly throughout the vasculature. Drs De Paepe and Malfait address heritable collagen disorders such as the Ehlers–Danlos syndromes (EDS), a heterogeneous group of diseases involving the skin, ligaments and joints, blood vessels and internal organs.

3; CI 15–35) and a previous child with haemophilia (RR 22; CI

3; CI 1.5–3.5) and a previous child with haemophilia (RR 2.2; CI 1.4–3.4). More than half of all Dutch haemophilia carriers underwent prenatal diagnosis. Several determinants were strongly associated Selleck Sunitinib with prenatal diagnosis. “
“Summary.  Sport is increasingly recommended for haemophilic patients due to physical and psychological benefits. ‘WATERCISE’ is a specific aqua-training programme for

haemophiliacs in which endurance, strength, coordination and mobility are trained. In the WAT-QoL study benefits and risks of regular WATERCISE training sessions were investigated in terms of health-related quality of life (HRQoL), physical functioning (PF), orthopaedic joint status (OJS), bleeding frequency and factor consumption. Patients in the WATERCISE group attended an aqua-training

programme once a week for 1 h over 12 months, patients in the control group did not. Patients were matched for clinical and demographic data. Information on clinical data, orthopaedic status, PF (HEP-Test-Q) and HRQoL were collected in both groups at baseline and at follow-up (6 and 12 months). Twenty-eight adult severely affected haemophilic patients (WATERCISE group: 10 haemophilia A (HA), 3 haemophilia B (HB) patients; control group: 12 HA and 3 HB patients) were enrolled (aged 40.68 ± 12.7 years). Baseline data (body mass indices, OJS, sportive activities, HRQoL and PF) were well distributed between groups. buy FK506 After 12 months the WATERCISE group reported a significantly better PF (MW = 65.22, SD = 11.3; MC = 52.5, SD = 15.0), especially for endurance (P < 0.004). Although always differently reported by the patients within the WATERCISE

group, HRQoL did not prove to be significantly different between groups. WATERCISE seems to Progesterone have a positive effect on the PF of patients suffering from haemophilia. These study findings need to be further investigated in a larger study group. “
“Summary.  While the majority of this session will deal with selected inherited vascular abnormalities that may manifest as a haemorrhagic disorder, the initial discussion by Dr Key will focus on the interplay between the vessel wall and components of the coagulation system, with a focus on haemophilia A and B. Although it is generally accepted that physiological haemostasis is triggered by contact of blood with tissue factor (TF), there remains some controversy regarding the cellular origin of TF in vivo. In addition, the initiation and propagation of thrombin generation are highly dependent on the balance of pro- and anticoagulant functions of endothelium, a profile that varies significantly throughout the vasculature. Drs De Paepe and Malfait address heritable collagen disorders such as the Ehlers–Danlos syndromes (EDS), a heterogeneous group of diseases involving the skin, ligaments and joints, blood vessels and internal organs.

13 Dendritic cells (DCs) are classified as professional antigen p

13 Dendritic cells (DCs) are classified as professional antigen presenting cells (APCs) and play a central role in both the innate and acquired immune responses. DCs are heterogeneous populations of cells. Migratory Protein Tyrosine Kinase inhibitor and resident DCs are involved in the maintenance of self-tolerance

and the induction of specific immune responses against invading pathogens. DCs act as APCs by phagocytosing pathogens and self-antigens and then presenting the antigens to T and B cells on their cell surface. DCs also produce several cytokines in response to stimulation signals from pathogen-associated molecular patterns (PAMPs) or whole bacteria. Thus, DCs contribute to immunological homeostasis by promoting inflammatory responses to pathogens, inducing tolerance to self-antigens,

and suppressing this website excessive immune responses.14 Dysregulation of DCs can therefore lead to autoimmune diseases and chronic inflammatory disorders. Abnormally strong immune responses to commensal bacteria, food antigens, and self-antigens have been reported in the pathogenesis of these diseases. The article by Long and colleagues in this issue of the Journal compares the phenotype and function of mouse lamina propria DCs (LPDCs) in the acute infectious and post-infectious phases of a PI-IBS mouse model (Fig. 1).15 The model used mice infected with Trichinella spiralis, which showed a prolonged disturbance in intestinal motility, with visceral hyperalgesia observed 8 weeks

after infection.16 In the acute infectious phase (2 weeks after infection), LPDCs displayed low CD86 and MHC class II molecule expression patterns and lesser ability to induce T cell proliferation, although endocytosis function was well maintained. On the other hand, in the PI-IBS phase (8 weeks after infection), LPDCs displayed increased CD86 and MHC class II expression patterns resulting in enhanced induction of T cell proliferation, while endocytosis function was decreased. These results demonstrate that post-infectious LPDCs in the mouse model display the phenotype with higher APC function. Interestingly, co-culture of naïve T cells with LPDCs in the acute infectious phase induced a Th2 response. In contrast, Fenbendazole co-culture of naïve T cells with LPDCs in the post-infectious phase induced Th1 and Th17 responses. Based on these findings, Long and colleagues concluded that phenotypical and functional alterations of LPDCs contribute to the development of PI-IBS. Studies of DC function in human IBS are few, but it has been reported that the plasma concentration of kynurenic acid, which is produced through the tryptophan degradation pathway regulated by indoleamine 2,3-dioxygenase (IDO), is increased in male patients with IBS.17 Since IDO is a key enzyme regulating the metabolism of tryptophan, which plays an important role in DC function, this finding may support the hypothesis that DC function is changed in patients with IBS.

This article is protected by copyright All rights reserved “

This article is protected by copyright. All rights reserved. “
“What is the appropriate selection standard for the treatment methods for hepatocellular carcinoma? The “Makuuchi group’s algorithm” (Fig. 2) is recommended as the basis for selecting appropriate Sorafenib mw treatment methods for

hepatocellular carcinoma (grade B). We specified a treatment algorithm for hepatocellular carcinoma based on three factors: degree of liver damage, number of tumors and tumor diameter. For patients with the severity of the liver damage categorized into class A or B, first, hepatectomy is recommended, regardless of tumor diameter, if a single tumor is present. However, local ablation therapy can also be selected if the severity of liver damage is class B and the tumor diameter is 2 cm or less (LF001781 level 2b). Second, hepatectomy or local ablation therapy is recommended when the number of tumors is two or three and their diameter is 3 cm or less (LF001781 level 2b). Third, hepatectomy or transcatheter arterial embolization (TAE) is recommended when the number of tumors is two or three and their diameter selleck chemicals llc is larger than 3 cm (LF062832 level 1b). Fourth, TAE or hepatic arterial infusion chemotherapy is recommended when the number of tumors is four or more (LF062832 level 1b; LF100333 level 3). For patients with class C liver damage, first, liver transplantation is recommended when the number of tumors is three or fewer and their diameter is 3 cm

or less (or a single tumor measuring ≤5 cm in diameter) and patients are 65 years of age or younger (LF005404 level 2a; LF111445 level 2b). Second, palliative treatment is recommended when the number of tumors is four or more. For patients with class A liver damage accompanied by vascular invasion, hepatectomy, TAE or hepatic arterial infusion chemotherapy may be selected, and for those with extrahepatic metastasis, chemotherapy is an option. Choosing between hepatectomy and local ablation therapy for patients with class A or B liver damage was specified based on Arii’s article that described the results of a multicenter study having the Tau-protein kinase largest scale of such an investigation

performed in Japan to date (LF001781 level 2b). The rationale for the selection of TAE was based on Llovet’s article on a randomized controlled trial (RCT) that demonstrated significant improvement in the prognosis of Child–Pugh class A or B patients with multiple hepatocellular carcinoma (LF062832 level 1b). For the selection of liver transplantation, Mazzaferro’s article on a prospective cohort study presenting the Milan Criteria (LF005404 level 2a) and Todo’s article on living donor liver transplantation (LF111445 level 2b) were used as rationales. Two RCTs of hepatectomy and local ablation therapy encountered problems with study designs, such that they were used only as references (LF101346 level 1b) (LF101357 level 1b). “
“We read with great interest the report by Serste et al.

In this issue of HEPATOLOGY, Kahraman et al13 report that hepati

In this issue of HEPATOLOGY, Kahraman et al.13 report that hepatic NK cells, expression of NK cell–associated cytotoxic mediators (such as tumor necrosis factor–related apoptosis-inducing ligand [TRAIL]), NKG2D, and MICA/B messenger RNAs in the liver are significantly elevated in nonalcoholic steatohepatitis (NASH) and, to a lesser extent, in nonalcoholic fatty liver (NAFL), when compared to normal healthy control livers. Immunohistochemical analyses reveal

that MICA/B proteins are detected from hepatocytes in patients with NASH and NAFL. Moreover, the expression of MICA/B messenger RNAs are positively correlated with NAS score and hepatocyte apoptosis in NASH. These findings suggest that the MICA/B protein levels are up-regulated in hepatocytes from patients with NASH through mechanisms that have yet to be identified. selleck screening library This is then followed by activation of hepatic NK cells that release TRAIL as a means of killing hepatocytes, and thereby inducing hepatocelluar damage in these patients. It is not clear whether NK cells only kill MICA/B-positive hepatocytes or if they also kill MICA/B-negative cells. This could be confirmed by performing double-staining to determine whether MICA/B protein and terminal deoxynucleotidyl transferase–mediated dUTP nick-end selleck compound labeling (TUNEL+) hepatocytes are colocalized. Whereas the molecular mechanism underlying up-regulation of hepatic MICA/B

in NASH and NAFL patients was not explored in the study by Kahraman et al.,13 it has been well documented that expression of NKG2D ligands are up-regulated through a variety of stimuli that have been collectively termed “cellular stress”, such as cellular transformation, viral infection, and/or DNA damage.2, 3 It is known that fat accumulation can generate oxidative stress-induced DNA damage in hepatocytes,14 which may contribute to the up-regulation of hepatic MICA/B http://www.selleck.co.jp/products/PD-0332991.html in patients with NASH and NAFL. Interestingly, Kahraman et al.13 also show that levels of MICA/B messenger RNAs correlate positively with stage of fibrosis, suggesting that MICA/B also contribute to the progression of liver fibrosis. However, recent studies using

murine models of liver fibrosis suggest that the NKG2D-ligand interaction triggers the killing of activated hepatic stellate cells (HSCs) by NK cells through a TRAIL-dependent mechanism, thereby inhibiting liver fibrosis.15, 16 Liver fibrosis is a common scarring response to virtually all forms of chronic liver injury and is characterized by HSC activation and accumulation of collagen in the liver. In normal healthy livers, HSCs are quiescent, storing large amounts of vitamin A (retinol). During liver injury or culturing on plastic dishes, HSCs become activated and differentiate into myofiboblast cells that produce collagen. Activated HSCs can also become senescent during chronic liver injury or after 9–15 passages in vitro.