25 Using a luciferase reporter, which was driven by the HBV surface promoter, we found that KLF15 increased luciferase activity in a dose-dependent manner by up to 80-fold (Fig. 1A and Supporting Fig. 1). This transactivation effect of KLF15 was specific to the HBV surface promoter, because it had little effect on the cyclin D1 promoter (Fig. 1B). Previously, we and others found that the NF-Y binding site (CCAAT box, designated as the M2 site) and two flanking Sp1 factor binding sites (Z1/Z2 sites) are critical for HBV surface promoter activity.1, 10,

12, JQ1 purchase 30 As shown in Fig. 1C, the transactivation effect of KLF15 on the surface promoter was dramatically reduced to approximately four-fold by the mutations in the Z1/Z2 site and completely abolished

by the mutation in the M2 site (Fig. 1C and Supporting Fig. 1). These results indicate that KLF15 is a potent activator for the HBV surface promoter, and that its optimal activity on the surface promoter requires intact Z1/Z2 and M2 sites. Because the HBV core promoter is activated by Sp1 and/or Sp1-like factor,34 we thought KLF15 might also be involved in its regulation. To determine whether KLF15 could also activate the HBV core promoter, two different core promoter reporters, pCP1.3x and pCP, were used for the studies. pCP1.3x was generated from an HBV genomic DNA fragment, in which a luciferase open-reading frame substituted the core open-reading MLN8237 solubility dmso frame in the parental construct, whereas the pCP contains only a 162–base pair HBV core promoter fragment. In both reporter constructs, the expression of the luciferase was under the control of the core promoter. As shown in Fig. 2A,B, KLF15 could also MCE activate the core promoter in a dose-dependent manner similar to the effect on the surface promoter (Fig. 1). Notably, we identified a sequence within the 162–base pair core promoter in pCP that matched exactly the KLF15 consensus binding sequence (GGGGNGGNG) reported by Uchida et al.25 Moreover, this sequence matched

an Sp1 or Sp1-like factor binding site (C region, site 3) identified by McLachlan’s group in the HBV core promoter.34 To determine whether this consensus sequence could be recognized by KLF15, we generated two mutant luciferase reporters, pCPm1 and pCPm2, in which two guanosine residues in the KLF15 consensus sequence were changed to thymidine (Fig. 2C). These two constructs were designed to disrupt possible KLF15 binding to the core promoter. In addition, the CPm2 sequence was designed to maintain the overlapping HBV X (HBx) protein-coding sequence. Hence, the exact same mutations can be introduced into the HBV genome to study their effects on HBV gene expression without the confounding effect of HBx mutations.28, 31, 32 Consistent with our predictions, mutations in the KLF15 consensus sequence abolished the ability of KLF15 to transactivate CPm1 and CPm2 (Fig. 2D).

Human PBMCs were isolated by Ficoll-Paque density gradient centrifugation from blood of health volunteer donors. The immune cells and MSCs were cultured in transwell system. LC3-II was detected by Western Blot

so as to measure autophagic flux. Monocytes transfected with LC3-GFP were treated in different co-cultured system respectively and then LC3+ spots were quantified by fluorescent microscopy. The Microarray was done by CapitalBio Corporation. Results: The hMSChireg induce an almost complete inhibition of IFN-γ secretion of PHA stimulated PBMCs whereas the residual ones induce only partial inhibition (5% vs 39% change in IFN-γ secretion Ku 0059436 at 1 : 20 ratio to PBMC). Also, hMSChireg can suppress TNF-α production to a much lower level than their counterpoint (41% vs 79% change in IFN-γ secretion at 1 : 20 ratio to PBMC). hMSChireg decrease the expression of IFN-γ and TNF-α more effectively (2% vs 19%, 5% vs 19%). In addition, hMSChireg

can induce Treg more effectively than the other part of MSCs (5.4% vs 3.3%), hMSChireg treated monocytes up-regulate their LC3-II gene expression while the effect of their counterpoint is weaker. hMSChireg more significantly enhance autophagy of macrophage (4.20 vs. 1.56 LC3+ spots/cell). gene expression profiles are generated from both hMSChireg and residual MSCs which show that the levels of COX-2, IL-1α, IL-1β, IL-6, IL-8 and IDO1 are significantly up-regulated in hMSChireg with an increased ability to secrete PGE2. Conclusion: MSChireg, as a unique subpopulation of MSC, more effectively suppress Th1 polarization of CD4+ T cells and induce Treg and at same time more significantly enhance IWR-1 autophagy. This indicates that MSChireg may not only contribute to inhibit excess inflammatory but also ameliorate the defective innate immunity in IBD. However, according to our previous data and others’ reports, even under inflammatory conditions only a proportion of MSC can be detected in the intestine, suggesting that additional mechanisms of immune suppression may be active. In addition,

enhancing binding of MSChireg enhances their migration to the inflamed colon and in turn may also be expected to potentiate their immunosuppressive MCE effects in vivo. So we hypothesize that MSChireg could lead to a more rapid clinical response and a dose reduction of cells, which could have profound effects on current treatment development programs. Key Word(s): 1. IBD; 2. MSC; 3. immunoregulatory; 4. in vitro; Presenting Author: LEI LIU Additional Authors: XIAOLAN ZHANG Corresponding Author: XIAOLAN ZHANG Affiliations: The Second Hospital of Hebei Medical University Objective: T helper (TH) 1 and TH17 cytokines have been reported to be involved in the genesis and maintenance of inflammatory bowel disease (IBD). Mesenchymal stem cells (MSCs) were described to suppress effector T-cell responses and have therapeutic effects in some immune disorders.

4 M). Taken together, our data suggest that AH-RPS

might maintain its clay-dispersing activity and inhibit mutual flocculation of microalgae and suspended clay in saltern brine. “
“The dinophysoid dinoflagellates are currently divided into three families: Amphisoleniaceae, Dinophysaceae (mainly Dinophysis Ehrenb. and Phalacroma F. Stein), and Oxyphysaceae, the latter including only one member, Oxyphysis oxytoxoides Kof. Phalacroma has been recently reinstated separately from Dinophysis, and its amended description is currently restricted to cells whose epithecae selleck kinase inhibitor were large but <1/4 of the cell length. With the aim of improving the phylogeny of Dinophysales, we obtained 54 new SSU rRNA gene sequences of 28 species. Taxon-rich SSU rDNA phylogenetic analysis showed that Dinophysales split into two major clades, one containing the Amphisoleniaceae (Amphisolenia F. Stein–Triposolenia Kof.) and the other containing the Dinophysaceae. The latter are divided into two well-supported sister groups, the Dinophysaceae sensu stricto (s.s.) (Dinophysis, Ornithocercus F. Stein, Histioneis F. Stein) and, tentatively, a separate family for the clade of the type and most of the Phalacroma species. Based on combined Daporinad research buy phylogenies of new SSU rDNA and available LSU rDNA

data, O. oxytoxoides (elongated epitheca, >1/4 of the cell length) branched with a strong support with the type of Phalacroma. We therefore propose Phalacroma oxytoxoides comb. nov. for O. oxytoxoides. Our SSU rDNA phylogeny also suggests that the assumed high intraspecific variability of Dinophysis hastata F. Stein hides a number of cryptic species. According to their distinct phylogenetic placement, the forms D. hastata f. phalacromides Jørg. and D. hastata f. uracanthides Jørg. should be erected at the species level. We propose for them the names Dinophysis phalacromoides comb. nov. and Dinophysis uracanthoides comb. nov. “
“At present, there is strong commercial demand for recombinant proteins, such as antigens, antibodies, biopharmaceuticals, and industrial enzymes, which cannot be fulfilled by existing MCE公司 procedures. Thus, an intensive search for alternative models

that may provide efficiency, safety, and quality control is being undertaken by a number of laboratories around the world. The chloroplast of the eukaryotic microalgae Haematococcus pluvialis Flotow has arisen as a candidate for a novel expression platform for recombinant protein production. However, there are important drawbacks that need to be resolved before it can become such a system. The most significant of these are chloroplast genome characterizations, and the development of chloroplast transformation vectors based upon specific endogenous promoters and on homologous targeting regions. In this study, we report the identification and characterization of endogenous chloroplast sequences for use as genetic tools for the construction of H.

We also examined whether isolated exosomes could re-enter cells and thereby play roles in intercellular processes or events. Methods Ganetespib and Results: Groups were established of healthy C57BL/6 mice and mice with acute liver failure (ALF) induced by a single i.p. LD50 dose of 500mg/kg acetaminophen (APAP). The extent of injury was established by liver tests and histology. Primary mouse hepatocytes were

isolated by collagenase perfusion and cultured on collagen and additives with IC50 dose of 20 mM APAP. Cytotoxicity was monitored by MTT assay. Hepatic injury was ameliorated by G-CSF treatment. Exosomes were isolated by established methods from blood sera and culture medium. miRNA samples were prepared from liver, hepato-cytes and exosomes including healthy controls and APAP- or APAP+GCSF-treated conditions. Small RNA libraries were prepared with commercial kits and next-generation sequencing was performed with the Ion Torrent platform followed by comprehensive bioinformatics analysis. The miRNA profiles of intact tissue, cultured hepatocytes

and exosomes differed markedly, indicating significant divergences at both quanti tative and qualitative levels. These differences were amplified after APAP-induced injury. Remarkably, while miRNA profiles of healthy and GCSF-treated liver samples re-converged along pattern similarity, profiles of exosome miRNA remained different and included multiple species of unknown impact. We found exosomes were avidly incorporated Compound Library cost in hepatocytes, including after i.v. injection into DPPIV- mice or after culture with hepatocytes, where DPPIV+ or dye-labeled exosomes were identified by staining methods. Moreover, in MTT assays of APAP cytotoxicity with responder

mouse or human hepato-cytes, exosomes from healthy cells, but not from APAP-treated cells proved cytoprotective. Conclusions: Hepatic exosomal content altered after injury and offers opportunities for correlation with cell type-specific changes and therapeutic 上海皓元医药股份有限公司 responses. Moreover, differences in cytotoxic outcomes after incorporation of healthy exosomes indicate these may serve other relevant roles for cell-cell communication in health or disease. Disclosures: The following people have nothing to disclose: Yogeshwar Sharma, Tatyana Tchaikovskaya, Preeti Viswanathan, David B. Rhee, Pilib O Broin, Tatyana Gor-bacheva, Alexander Y. Maslov, Aaron Golden, Sanjeev Gupta BACKGROUND/AIM: Heat shock factor 1 (HSF1), is the master regulator of genes encoding molecular chaperones and is involved in cellular processes such as stress response, cell differentiation and carcinogenesis. Recent studies identified a HSF1-regulated transcriptional program specific to high malignancy and distinct from the classical HSF1-induced heat shock response. We have investigated the expression of HSF1 during tumour formation and after Radiofrequency Ablation (RFA) in vivo.

Using a combination of expression studies,

macrophage depletion, and ex vivo coculture, the authors propose a model whereby the balance between Notch and Wnt signaling in ADCs determines the proper ratio of BECs and hepatocytes during liver regeneration. They report their findings in the March issue of Nature Medicine.20 The authors begin their studies with a detailed immunohistochemical analysis and 3D reconstruction to characterize what they refer to as the hepatic progenitor cell “niche”—the population of nonparenchymal cells that arise alongside ADCs during liver injury. Using two different models: a murine choline deficient ethionine supplemented (CDE) model, which is thought to cause predominantly hepatocellular injury, and a DDC diet model, which is thought to cause predominantly biliary injury, the authors find two distinct patterns of infiltrating cells adjacent to the ADCs. Following Nutlin-3a in vivo hepatocyte injury, Kupffer cells were found in close proximity to the ADCs, Selleck JNK inhibitor whereas following biliary injury,

ADCs were associated with portal fibroblasts and thick bands of collagen. Based on this difference in relative proximity, Boulter et al. hypothesized that these two cell populations (Kupffer cells and portal fibroblasts) might influence ADC behavior differently. As portal fibroblasts express high levels of the Notch ligand Jagged1, Boulter et al. treated isolated ADCs with the γ-secretase inhibitor DAPT, which inhibits the Notch pathway. They observed a decrease in the expression of biliary markers, consistent with the known role of Notch signaling MCE in biliary fate and identity. Furthermore, treatment of animals with DAPT in vivo led to a decrease in the number of ADCs. Interestingly, expression of the hepatocyte marker HNF4α was not increased by DAPT treatment, indicating that pharmacological inhibition of Notch was not sufficient to direct the ADCs to differentiate to the hepatocyte lineage. The authors observed that a number of Wnt pathway target genes, including

Numb, were activated in the ADCs in both patient and murine hepatocellular injury models. Hence, they investigated whether Numb, which inhibits Notch signaling by facilitating proteasome-mediated degradation of the Notch receptor, might induce ADCs to differentiate into hepatocytes. To test their hypothesis in vivo, they activated canonical Wnt signaling in ADCs by expressing a constitutively active form of β-catenin in these cells, an experiment that resulted in an increased number of hepatocytes exhibiting nuclear β-catenin in staining. Importantly, although the authors interpreted this finding as evidence that β-catenin activation directs ADCs to differentiate to the hepatocyte lineage, the absence of formal lineage tracing precludes such a conclusion. Finally, Boulter et al. turned their attention to the cells that might be providing activating signals for these pathways.

One study observed HBeAg positive patients, 233 treated with IFN and 233 untreated for 6.8 years, with cancers detected in 2% of treated patients and 7%

of untreated controls, showing carcinogenesis significantly reduced in the IFN therapy group (P < 0.025).[90] On the other hand, the other study of HBeAg positive patients, 208 treated with IFN and 203 untreated, found no significant difference in the rate learn more of carcinogenesis (2.9% vs 0%).[260] Although many other studies have evaluated the relationship between IFN therapy and carcinogenesis,[261-266] they have all been cohort studies and their results do not consistently demonstrate a carcinogenesis suppressor effect for IFN. In these cohort studies, the carcinogenesis rate in the control group (untreated patients) varies greatly from 0% to 30.8%, and the rate including patients with cirrhosis also varies from 0% to 100%, with considerable differences in subject clinical backgrounds. These differences

in the clinical background of applicable cases may be related to the variations in the reported carcinogenesis suppression effect of IFN. PKC412 chemical structure A number of meta-analyses have examined the relationship between IFN therapy and carcinogenesis. One analysis of 11 studies comprising 1006 patients treated with IFN and 1076 untreated controls found IFN therapy significantly reduced the carcinogenesis risk ratio to 0.59.[267] Another meta-analysis of 8 studies found that, although carcinogenesis was suppressed in IFN treated patients compared to untreated controls medchemexpress (risk difference 5.0%), the carcinogenesis suppression

effect was found in a subgroup of ethnic Asians, where the carcinogenesis rate in the untreated controls was ≥10%, and ≥70% of subjects were HBeAg positive.[268] A third meta-analysis of 7 studies evaluated the therapeutic effect of IFN in patients with cirrhosis, 122 cases of HCC developed in 1505 patients with liver cirrhosis, and a carcinogenesis risk difference of 6.4% in IFN treated patients compared to untreated controls.[269] The authors discussed that, although all 7 studies indicated a tendency for IFN therapy to suppress carcinogenesis, only 3 studies showed a significant difference, of which 2 studies were results from Asia. Then they concluded that the overall significant difference disappeared with elimination of the last 2 Asian studies, and no firm conclusion was made concerning carcinogenesis suppression by IFN therapy. Another meta-analysis of 12 studies examining 1292 IFN treated patients and 1450 untreated controls, IFN therapy significantly reduced the carcinogenesis risk ratio to 0.66.[270] A sub-analysis indicated that carcinogenesis was suppressed by IFN therapy in liver cirrhosis patients (11.6% vs 21.5%, risk ratio 0.53, 95% CI: 0.36–0.78), whereas for non-cirrhosis patients the cancer rate was low, 0.9% in treated patients and 1.1% in untreated controls, showing no significant difference.

9 BU in the HIGS study and >0.6 BU in the MIBS study. Genotyping of the F8 mutation was performed as previously described [24, 25]. Statistical tests were performed in PASW 18.0

for Windows (SPSS Corporation, Chicago, IL, USA) and in Excel 2007 for Windows (Microsoft, Redmond, WA, USA). The Mann–Whitney U test was used to test the difference in median age between patients with and without non-neutralizing FVIII-antibodies. A P-value less than 0.05 was considered statistically significant. ELISA assays were performed in the 201 patients without a current inhibitor. Antibodies towards a mixture of all three rFVIII products were found in 43 (21.4%) patients, of whom 23 had no previous history of an inhibitor, corresponding to a frequency of NNA of 18.9% (23/122) (see Fig. 1). Within this subgroup PD-1/PD-L1 assay of 23 subjects, eight were ELISA-positive towards both the mixture of coating antigens and each antigen alone (see Table 1). The remaining 15 subjects TSA HDAC supplier showed a heterogeneous antibody response. In all but two cases, antibodies were identified against both full-length molecules, whereas only 10 of the plasma samples contained antibodies against the BDD-molecule. With subject plasma No. 1, the ELISA was negative

in the presence of both full-length molecules, but in No. 3, with only one of them. Immune tolerance induction had been initiated in 66 of the 79 subjects with a history of inhibitory FVIII antibodies (see Fig. 1). ITI was on-going in three

cases at the time of blood sampling. All 上海皓元 three of these were reported by the investigator to have a negative Bethesda titre; however, one had a positive ELISA assay. Failed ITI treatment was reported in four subjects, even though all four had a negative Bethesda titre. In two of these, an antigenic response was detected with the ELISA assay. Fifty-nine (89.4%) subjects were considered successfully treated with ITI. In 35 of the subjects, success was defined as having a negative Bethesda titre, a normal half-life (T1/2) and/or a normal FVIII recovery. In the remaining patients, ITI outcome was either confirmed exclusively with a negative Bethesda titre, or the confirmatory method was not specified. Overall, antibodies towards the FVIII mixture were found in plasma samples from 15 (25.4%) of the 59 subjects considered successfully treated. In Table 2, the antigenic responses of the nine HIGS patients with data available on the defined success criteria and the product used at inhibitor detection are shown. In 3 (33.3%) of the subjects, the ELISA assays were negative only towards the product the patient had been treated with, that is the BDD-rFVIII in two cases (patients No. 7 and 9), and full-length in one (patient No. 1). In this latter patient, it is noteworthy that a Bethesda titre of 0.7 BU was stated despite a successful ITI treatment. Likewise, a titre of 0.8 BU was reported in patient No. 4. For subject No.

4C). Furthermore, no other hepatic miRNA besides miR-27 was predicted to have high-confidence ORF or 3′ UTR sites in ANGPTL3. We placed 8-week-old Apoe−/− female mice on a high-fat/high-cholesterol diet (21% fat, 7.5% cocoa butter), which has been shown to induce severe hypercholesterolemia and advanced atherosclerosis.40, 41 To confirm the expected physiologic effects of this diet, we measured plasma total cholesterol and triglyceride levels after 4 weeks. We observed a significant increase

in plasma cholesterol levels (4.6-fold, unpaired t test, P < 0.001; Fig. 6A) and a significant decrease in plasma triglycerides (≈63% loss, unpaired t test, HSP inhibitor P = 0.003; Fig. 6B) in the Apoe−/− mice fed the atherogenic diet. After 4 weeks on the atherogenic diet, levels of both mature miR-27b (1.58-fold, unpaired t test, P = 0.09) and pri-miR-27b (unpaired t test, P = 0.03) were increased in the liver; Fig. 6C,D). Based on this finding, we next assessed the hepatic expression of miR-27b target genes. Consistent with the in vitro results, mRNA levels of both Angptl3 (≈30% loss) and Gpam (≈22% loss) were reduced (Supporting Fig. S4); however, these observations were outside of statistical significance. In this study we provide in silico, in vitro, and in vivo evidence that miR-27b is a strong candidate regulatory hub in lipid selleck compound metabolism. Based on Monte-Carlo

simulations, miR-27b was predicted to target significantly more lipid metabolism-associated genes than expected by chance and more than any other hepatic miRNA. Two of the other miRNAs

predicted to be regulatory hubs in lipid metabolism (Fig. 1B,C), miR-365 and miR-125, have previously been shown to play roles in either adipocyte differentiation42 or in cellular lipid uptake,27 respectively, thus validating our approach. High-throughput small RNA sequencing and real time quantitative PCR analysis revealed that miR-27b is ≈3-fold up-regulated in the livers of mice on a high-fat diet. MiR-27b is encoded with miR-23b and miR-24-1 in the same cistron on mouse chromosome 13. Small RNA sequencing results suggest that both miR-23b and miR-24 are also up-regulated in the 上海皓元医药股份有限公司 liver of wildtype mice after a high-fat diet by ≈2.2-fold and ≈7.9-fold, respectively. However, we did not detect any change in the levels of their primary transcript, which suggests that: (1) posttranscriptional mechanisms are completely responsible for the observed increase in the mature miRNA levels, or (2) there is an increase in transcription of the miR-27b locus but also a concomitant increase in the rate of processing of the primary transcript (i.e., decreased pri-miR-27b stability). In contrast, Apoe−/− mice on an atherogenic diet were found to have increased hepatic levels of both mature miR-27b and pri-miR-27b.

6) and nonentangled (γ  =  1.0) conditions

from tag-derived relative submergence depths (1.81 m and 4.25 m, respectively). We then calculated the drag on the body, Dw (N), as (6) Line lying flush with the body surface produces a surface protuberance that may disrupt fluid flow over the body, affecting body drag. The total drag of the system is not simply the sum of the drag on the body and on the element, but also High Content Screening the interference between the elements (interference drag) (Blake 1983). The magnitude of interference drag varies nonlinearly with the position (% of l) and height of the protuberance (p, m) compared to the length of the body (l, m) (Jacobs 1934, Blake 1983). As protuberance height is increased from p = 0 to p = 0.001 l (e.g., from 0 to 1.25 cm diameter line) interference drag is comparatively small, on the order of 10% of the drag of the element. Increases in drag over this height scale are slow due to the protuberance being

in the body’s boundary layer (δ); however, they should not be considered negligible (Jacobs 1934). For this height scale, the interference drag coefficient of a protuberance j(CDI,j) is (7) where we calculated boundary layer thickness (δ, m) at the location of protuberance j (distance from leading edge, lx,j; m) based on the ratio between the maximum diameter and the diameter at the location of protuberance j(dx,j) as (8) We Selleckchem Trichostatin A then calculated the total interference drag, DI (N), as the sum of the interference drag associated with all n protuberances on the frontal projection of the body (Hoerner 1965): (9) Bodies in water have a shielding effect that reduces drag on objects floating in their wake (Hoerner 1965).

In the wake 上海皓元医药股份有限公司 of the first body, the dynamic pressure is reduced and drag is decreased over the distance of x/d = 2, where x is the distance between the two bodies (m). Organisms take advantage of reduced drag in a wake by forming queues (e.g., Fish 1995, Bill and Herrnkind 1976), and the same theory holds for an animal towing accessory gear in its wake. Any object at a distance x/d < 2 should experience a reduction in drag by a factor of approximately 0.75 (Hoerner 1965). We calculated the total drag, DT (N), on an entangled whale: (10) where Db is the drag on tethered buoys or other accessory gear, Dl is the drag on the attached line, DI is the interference drag, and a is the shielding factor, based on the spacing distance, x, between the body and the towed gear where if x/d < 2, a = 0.75, and if x/d > 1, a = 1. In this study, we measured (Db + Dl) empirically. We derive the total power input (PI,T; W) required for propulsion at a certain speed under any calculated drag condition (generic D) as (11) where PL is locomotory power, and PI,B is power input for standard metabolism, both in W, and η is an efficiency coefficient of 0.15 (Fish 1993, Hind and Gurney 1997).

As a result of the delayed

graft function, the patient required intensive care unit treatment for 1 week before the liver graft function improved. He was able to be discharged in good general condition on postoperative day 21. Case 3: A 58-year-old male presented with multiple colorectal liver metastases in the right hemi-liver as well as in segment II, III, and 10 months after resection of the primary rectal tumor followed by 5 cycles of chemotherapy containing Folfox and Avastin. A work-up including positron emission tomography and CT failed to identify extrahepatic metastases. A curative resection was considered, A-769662 ic50 involving a right hemi-hepatectomy associated with wedge resections of the tumors located in the left hemi-liver. The estimated weight of the remnant liver after surgery was 320 g, reflecting 26% of the whole-liver volume and RLBW of 0.5% (Fig. 1). Postoperatively,

the patient developed severe encephalopathy, large amounts of ascites, hyperbilirubinemia up to 300 μmol/L (17.5 mg/dL), and persistent coagulopathy with a prothrombin time below 30%. He subsequently developed renal failure requiring replacement therapy by postoperative day 5 and pulmonary edema requiring reintubation. He died in the intensive care unit on postoperative day 13. These three cases illustrate the wide spectrum and clinical impact of SFSS, which possibly represents the most serious complication after partial OLT Mitomycin C in vivo and major hepatectomy. Preventing SFSS and understanding the underlying mechanisms may provide the most significant impact in improving outcome of many patients with liver diseases subjected to surgery or transplantation. 上海皓元医药股份有限公司 The liver has the fascinating ability to sustain its function, even after major reduction of its parenchymal mass, and regenerates to its normal size within a few days.1 However, there is a critical mass below which liver function cannot be preserved, leading to the widely used but poorly defined entity of SFSS, which is characterized by encephalopathy, coagulopathy, ascites, prolonged hyperbilirubinemia, and hypoalbuminemia, and is often

associated with renal impairment followed by pulmonary failure and ultimately death. A few attempts were made to standardize the definition of SFSS to enable meaningful comparisons over time and among different institutions. At this point, however, no consensus has been reached, making comparisons of studies in the literature nearly impossible. We previously attempted to define SFSS3 by the presence of two of the following three factors (bilirubin >100 μmol/L [5.85 mg/dL], international normalized ratio >2 [prothrombin time ∼33%], and the presence of encephalopathy ≥grade 3) on 3 consecutive days over the first postoperative week. SFSS should be, of course, considered only after exclusion of other causes of liver failure such as technical problems including outflow obstruction and immunological or infectious complications.