sGP73 levels were detected in subjects

of group D (n = 287) by enzyme-linked immunoassay. GP73 expression increased gradually BTK inhibitor from NC, CHB, PTL to high-grade AH and HCC at both protein and mRNA levels (P < 0.05), while sGP73 in the HCC group was lower than in the liver cirrhosis (LC) group (P < 0.001). Both tGP73 and sGP73 levels were negatively associated with tumor size and tumor–node–metastasis stage, and tGP73 levels were positively associated with tumor differentiation. The high-tGP73 group showed significantly better overall and disease-free survival than the low-tGP73 group (P = 0.008, P = 0.018). Multivariate analysis revealed that the tGP73 level was an independent prognostic factor for HCC, but not sGP73. GP73 expression pattern suggests that the regulatory mechanism of GP73 is related to the progression of chronic liver diseases. Furthermore, a high level of tGP73 is a favorable prognostic factor for HCC. "
“There are several murine models described with features similar to human primary biliary cirrhosis (PBC). Among these models, the one which has the closest serologic features to PBC is a mouse with a T-cell-restricted expression of the dominant negative transforming selleck chemicals growth factor β receptor type II (dnTGFβRII).

Our work has demonstrated that CD8+ T cells from dnTGFβRII mice transfer autoimmune cholangitis to Rag1−/− recipients. However, it remained unclear whether the autoimmune cholangitis was secondary to an intrinsic function within CD8+ T cells or due to the abnormal

Sulfite dehydrogenase TGFβR environment within which CD8+ T cells were generated. To address this mechanistic issue, we used our dnTGFβRII, OT-I/Rag1−/−, OT-II/Rag1−/− mice and in addition generated OT-I/dnTGFβRII/Rag1−/−, and OT-II/dnTGFβRII/Rag1−/− mice in which the entire T-cell repertoire was replaced with ovalbumin (OVA)-specific CD8+ or CD4+ T cells, respectively. Importantly, neither the parental OT-I/dnTGFβRII/Rag1−/− mice and/or OT-II/dnTGFβRII/Rag1−/− mice developed cholangitis. However, adoptive transfer demonstrated that only transfer of CD8+ T cells from dnTGFβRII mice but not CD8+ T cells from OT-I/Rag1−/− mice or from OT-I/dnTGFβRII/Rag1−/− mice transferred disease. These data were not secondary to an absence of CD4+ T cell help since a combination of CD8+ T cells from OT-I/dnTGFβRII/Rag1−/− and CD4+ T cells from OT II/dnTGFβRII/Rag1−/− or CD8+ T cells from OT-I/dnTGFβRII/Rag1−/− with CD4+ T cells from OT-II/Rag1−/− mice failed to transfer disease. Conclusion: Defective TGFβRII signaling, in addition to clonal CD8+ T cells that target biliary cells, are required for induction of autoimmune cholangitis.

Gomez et al.[9] have further contributed to our understanding of decompensation in cirrhosis. In particular, the group focused on patients from Latin America with the main objective to evaluate the 6-year cumulative incidence AG14699 of overall mortality or transplantation, HCC, and major clinical outcomes of hepatic decompensation. The authors evaluated a large Cuban cohort of HCV patients with cirrhosis with two different

stages of compensated disease with the absence (stage 1) and presence of varices (stage 2). The study was conducted as a prospective longitudinal “inception cohort” study. Between 2004 and 2007, 402 patients were included in the study if they were >18 years of age, had confirmed

Staurosporine molecular weight diagnosis of cirrhosis based on clinical, laboratory, and imaging findings, or histology, without a history of decompensation and absence of alcoholism. Patients were excluded if there was concurrent liver disease, concomitant diseases with reduced life expectancy, psychiatric disease, or HCC. Noninvasive studies were relied on to make the diagnoses of cirrhosis in some patients. This may influence the findings, as noninvasive testing can occasionally misdiagnose cirrhosis. The primary outcome of the study was overall mortality or liver transplantation. Secondary outcomes were diagnosis of HCC, variceal hemorrhage, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, jaundice, and development of varices in patients (in stage 1 patients only). Similar to previous studies, the authors found that patients with stage 2 disease with varices had poorer outcomes when compared to stage 1 disease without varices. The cumulative overall mortality or liver transplantation at 312 weeks was significantly lower in stage 1 cirrhosis without varices (15%) compared to stage 2 cirrhosis with varices (45%). Also consistent with previously published results, the incidence

of HCC at 312 weeks was significantly lower in patients with stage 1 cirrhosis (9%) compared to stage 2 cirrhosis (29%). Notably, not patients were screened for HCC every 6 months with liver ultrasonography and α-fetoprotein determination throughout the study. Similar to previous findings, ascites was the most common first decompensating event, at 15%. Variceal hemorrhage and hepatic encephalopathy each occurred as the first decompensating event in 5% of patients. The occurrence of clinical decompensation was different in patients with stage 1 and 2 cirrhosis. One possible explanation is that patients both with (higher HVPG) and without varices (lower HVPG) were included. Patients with stage 2 cirrhosis with varices had a higher 6-year cumulative incidence of decompensation at 66% but stage 1 patients without varices had a significantly lower incidence, at 26%.

8C). This may help explain a lack of correlation between inflammation and hepatocellular damage (serum ALT levels) observed in some patients with chronic liver diseases.8-13 In our study, injection with CCl4 induced much higher levels of systemic and hepatic inflammation in STAT3 mice than in wild-type mice, suggesting that STAT3 in myeloid cells plays an important role in inhibiting inflammation in a

model of CCl4-induced liver injury. This is consistent with previously well-documented studies showing the anti-inflammatory effects of STAT3 in ACP-196 myeloid cells using various models of organ injury.26-28 Surprisingly, despite higher levels of inflammation in STAT3 mice, they had much lower serum ALT levels and less liver necrosis than wild-type mice after CCl4 administration.

The resistance of STAT3 mice to CCl4-induced liver necrosis may be attributable to either the impaired ability of STAT3-deficient neutrophils/macrophages to induce hepatocellular damage or the resistance of hepatocytes to CCl4-induced hepatocellular damage in STAT3 mice. Several lines of evidence suggest that it is the second mechanism that contributes to reducing liver necrosis in STAT3 mice because of enhanced STAT3 activation in the liver. The hepatotoxicity of CCl4 is mediated by the direct induction of hepatocyte damage RG7204 mw and indirect activation of Kupffer cells/macrophages and neutrophils.14 Activated Kupffer cells/macrophages produce free radicals and proinflammatory cytokines such as TNF-α that further trigger hepatocellular damage and induce neutrophil accumulation and activation.2, 5 Activated neutrophils can cause hepatocyte damage by releasing oxygen species and proteases.2, 5 We have

previously shown that Kupffer cells from STAT3 mice produce much higher levels of reactive oxygen species and TNF-α compared with those from wild-type mice.27 By using four different assays, Lee et al.29 previously demonstrated that STAT3-deficient neutrophils mature normally and are functional. In the Sulfite dehydrogenase current study we also confirmed that STAT3-deficient neutrophils from STAT3 mice are functional in vitro because they produced a similar respiratory burst after phorbol 12-myristate 13-acetate stimulation compared with phorbol 12-myristate 13-acetate–stimulated wild-type mouse neutrophils (Supporting Fig. S1c). Moreover, an additional deletion of STAT3 in hepatocytes restored liver necrosis in STAT3 mice after CCl4 administration, suggesting that neutrophils from STAT3 mice are functional in vivo. Collectively, these findings suggest that STAT3-deficient macrophages and neutrophils in STAT3 mice have normal ability to induce inflammatory responses and hepatocellular damage, and that the reduced liver necrosis observed in STAT3 mice is not attributable to a defect in STAT3-deficient macrophages and neutrophils to induce hepatocellular damage.

RUVBL1 bound

F-actin in cell protrusions, and increased concentration of G-actin and additional formation of actin filaments in cell protrusions. Conclusion: RUVBL1 contributes to the formation of membrane protrusions by promoting peripheral actin polymerization. These RUVBL1-actin interactions enhance the invasive properties of PDAC cells. Inhibition of binding between RUVBL1 and actin filaments may be a rational approach MAPK Inhibitor Library to a targeted molecular therapy for PDAC because any such therapy would inhibit the formation of cell protrusions and consequently limit the motility and invasiveness of PDAC cells. Key Word(s): 1. pancreatic ductal adenocarcinoma; 2. AAA + ATPase; 3. invasiveness; 4. cell protrusion; 5. actin polymerization Presenting Author: MASAHIKO UCHIDA

Additional Authors: TAICHI NAKAMURA, TETSUHIDE ITO, MASAYUKI NAKAYAMA, HIROYUKI SAKATA, RYUICHI IWAKIRI, KAZUMA FUJIMOTO Corresponding Author: MASAHIKO UCHIDA Affiliations: Kyushu University, Kyushu MK-2206 concentration University, Saga University, Saga University, Saga University, Saga University Objective: Chronic pancreatitis (CP) worsens with drinking, and pancreatic stellate cells (PSCs) play an important role in the pathogenesis of alcoholic CP. Fractalkine is chemokines, and membrane type and soluble type is present. A membrane-bound extracellular region is cut by sheddase, and soluble type fractalkine shows migration activity for the inflammatory cell with CX3CR1 (fractalkine receptor). Serum levels of fractalkine (CX3CL1) are elevated in patients with alcoholic CP, however the mechanism remains unclear. This study aims to determine the effects of cytokines, pathogen-associated molecular patterns (PAMPs), and ethanol and its metabolites on CX3CL1 secretion by PSCs. Methods: Male Wistar/Bonn Kobori (WBN/Kob) rats were used as models GPX6 of CP in vivo. PSCs were isolated from 6-week-old male Wistar rats.

The effects of cytokines, PAMPs, and ethanol on chemokine production and activation of signaling pathways in PSCs in vitro were examined by real-time reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and enzyme-linked immunosorbent assay. Results: Expression of CX3CL1 and matrix metalloprotease (MMP)-2 was increased in the pancreas of WBN/Kob rats. The rat PSCs expressed CX3CL1, MMP-2, and a disintegrin and metalloprotease domain (ADAM) 17. Cytokines and PAMPs induced CX3CL1 release. Ethanol synergistically increased CX3CL1 release via ERK and ADAM17 activation in PSCs. Several cellular signaling cascades are activated by CX3CL1 in PSCs and associated with cell proliferation. Conclusion: We demonstrated for the first time that ethanol synergistically increased CX3CL1 release from PSCs in part through activation of ERK and ADAM17. This might be one of the mechanisms of serum CX3CL1 elevation and disease progression in patients with alcoholic CP. Key Word(s): 1. chronic pancreatitis; 2. PSCs; 3. chemokine; 4.

Proven CCR2/CCR5 antagonism, antifibrotic effects in animal models and extensive clinical safety data all support clinical

studies of CVC in liver fibrosis. Disclosures: Melanie Thompson – Advisory Committees or Review Panels: Janssen/Tibotec Therapeutics (Data Safety Monitoring Board), Viiv Healthcare (Data Safety Monitoring Board); Grant/Research Support: Bristol Myers Squibb, Inc. (via AIDS Research Consortium of Atlanta), Gilead Sciences (via AIDS Research Consortium of Atlanta), Geovax, learn more Inc. (via AIDS Research Consortium of Atlanta), Kowa Research Institute (via AIDS Research Consortium of Atlanta), Pfizer Inc. (via AIDS Research Consortium of Atlanta), Janssen/Tibotec Therapeutics (via AIDS Research Consortium

of Atlanta), Merck & Co. (via AIDS Research Consortium of Atlanta), Tobira Therapeutics (via AIDS Research Consortium of Atlanta), Viiv Healthcare (via AIDS Research Consortium of Atlanta) Will Chang – Employment: Tobira Therapeutics Inc. Helen Jenkins – Employment: Tobira Therapeutics, Inc. Millie Gottwald – Stock Shareholder: Gilead Sciences, Alexza Pharmaceuticals Eric Lefebvre – Employment: Tobira Therapeutics Inc., San Francisco, CA, USA The following people have nothing to disclose: Amy Flynt Background & aims: HBV related liver fibrosis (HRLF) has been shown to involve complex interactions in genomics. Methods: 143 patients were divided into 3 groups Vadimezan cell line including control, Fibrosis and HCC. Affymetrix GeneChip was used. Genome data analysis was obtained by GeneSpring GX software, Significant Analysis of Microarray (SAM) and Prediction Analysis of Microarray Interleukin-2 receptor (PAM). Then qRT-PCR was used to verify predictor

genes. Results: The expression pattern of 678 significant genes identified by SAM showed different feature in significant HRLF (>S2). A subset of 18 predictor genes, which were identified by PAM, was defined to have “Fibrotic Risk” signature of HRLF. Six predictor genes were differentially expressed among S4, S1-S3 and S0 group (Figure 1). AUROCs of 6 genes were 0.85-0.88 in diagnosing significant HRLF (>S2). Total 6 predictor genes including CD24, CXCL6, EHF, ITGBL1, LUM and SOX9 were found to have AUROCs among 0.90-0.96 in discriminating cirrhosis. Univariate logistic regression analysis also identified their expression in liver tissue associated with cirrhosis. Conclusions: These findings provide a molecular portrait of genomes in HRLF. A set of 6 “Fibrotic Risk” genes are promising predictors for diagnosis of advanced stages of presymptomatic HBV related fibrosis.

, MD (Early Morning Workshops, Meet-the-Professor Luncheon) Consulting: Salix, Abbott, Merck, Lilly, Enterome, Aegerion Grant/Research Support: Intercept, Lilly, GenFit, Gilead, Enterome, Cumberland, Galectin Content of the presentation does not include discussion

of off-label/investigative use of medicine(s), medical devices or procedure(s) Chang, Kyong-Mi, MD (Early Morning Workshops, Parallel Session) Stock Shareholder: BMS (spouse employment) Chapman, Roger W., MD, PhD (Early Morning Workshops) Advisory Committees or Review Panels: falk, takeda Speaking and Teaching: roche Stock Shareholder: gilead Content of the presentation does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s) Chapman, William C., MD (SIG Program) Nothing to disclose Content of the buy LY2157299 presentation does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s) Charlton, Michael R., MD (AASLD Postgraduate Course, AASLD/ILTS Transplant Course,

Early Morning Workshops) Nothing to disclose Content of the presentation does not include discussion of off-label/investigative http://www.selleckchem.com/products/PD-0332991.html use of medicine(s), medical devices or procedure(s) Chavin, Kenneth D., MD, PhD (Plenary Session, Transplant Surgery Workshop) Advisory Committees or Review Panels: Novartis Grant/Research Support: Bridge to Life, Novartis, Sanofi Chojkier, Mario, MD (Parallel Session) Nothing to disclose Chung, Raymond T., MD (Early Morning Workshops, Meet-the-Professor Luncheon, Parallel Session) Advisory Committees or Review Panels: Idenix Consulting: Enanta Grant/Research Support: Gilead, Merck, Mass Biologic, Gilead Clark, Jeanne M., MD (AASLD/IASL Symposium) Nothing to disclose Content of the presentation does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s) Colombo, Massimo, MD (Parallel Session) Advisory Committees or Review Panels: Bristol-Meyers

Squibb, Schering-Plough, Roche, Gilead, Janssen Cilag, Achillion Grant/Research Support: Bristol-Meyers Squibb, Roche, Gilead Speaking and Teaching: Glaxo Smith-Kline, Bristol-Meyers Squibb, Schering-Plough, Roche, Novartis, Gilead, Vertex Baricitinib Copple, Bryan, PhD (Parallel Session) Nothing to disclose Crabb, David W., MD (Federal Focus) Nothing to disclose Content of the presentation does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s) Crippin, Jeffrey S., MD (AASLD Postgraduate Course) Consulting: Bayer Speaking and Teaching: Vertex, Genentech, Salix Content of the presentation does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s) Curry, Michael P.

21 Very recently, Spechler et al.4 have reported that the authors of a recently drafted Technical Review on BE commissioned by the American Gastroenterological Association

(AGA) considered the data summarized in the previous paragraph and, as a result, concluded that the “intestinal-type metaplasia only” definition should be discarded, in favor of the following: (Barrett’s esophagus is) . . . “the condition in which any extent of metaplastic columnar epithelium that predisposes to cancer development replaces the stratified squamous epithelium that normally lines the esophagus”.4 This circuitously worded definition still clings to the illogical concept that malignant potential should be a requirement for any definition of BE, but this AZD8055 chemical structure is no longer of practical importance if

it is accepted Maraviroc cost that all types of BE mucosa carry a risk for malignant change. The wording of this new definition conveys more than a whiff of political struggle and will bamboozle some readers, especially those whose first language is other than English, but still, this is real progress! Oddly, at the time of finalizing this article, there is no indication when this review will be published in Gastroenterology, the established journal for publication of AGA Technical Reviews. The Montréal workshop12 recommended the term “endoscopically suspected esophageal metaplasia (ESEM)”, pending histological confirmation, rather than “suspected BE”. This was driven by concerns of participants from the USA that the word mafosfamide “Barrett” causes major, unjustified loadings to life insurance premiums.12 This is a real issue that needs to be addressed, but this problem must not influence the clarity

of clinical terminology around the world; specifically, it is unjustified to coin yet another code term that would, in time, presumably be discovered and acted on with the same prejudice by insurance companies in the USA. This is a field that needs de-, rather than re-coding! There is now general acceptance that BE is an acquired abnormality. There remain major gaps in our understanding of factors that lead to its development and the factors that trigger progression to dysplasia and EA. Reflux disease is proven to be a major pathogenetic factor for development of BE,2–4 even though in some it is symptomatically mild or silent. In the minority of BE patients with metaplastic segments longer that 3 cm, gastroesophageal competence is usually severely impaired. Limited data also indicate that metaplastic segments shorter than 3 cm are associated with reflux disease. A careful search for BE (defined as at least 3 cm of metaplasia) in 733 unselected post-mortems revealed seven cases of which only two had been diagnosed during life. After adjustment, this was interpreted as showing that only 1 in 21 cases of BE is recognized during life.

It has been Gemcitabine proposed that pretreatment with PPI decreases the efficacy of H. pylori eradication treatment. With so many patients being treated with PPI for a period prior to being investigated for dyspepsia, this could have obvious negative

clinical implications. Two studies published on this topic this year, however, failed to support this hypothesis nor does it appear to have any impact on symptom severity and quality of life [38,39]. There is a cohort of patients, however, for whom the use of a PPI for H. pylori eradication might be undesirable, for instance those on dual antiplatelet therapy with coronary stents or patients with allergies and intolerances. A trial was published this year on a new-generation histamine-2 Paclitaxel cell line receptor antagonist, lafutidine, that has antisecretory properties. This study suggested that as part of a standard

triple-therapy regimen, similar rates of eradication could be achieved with lafutidine as with lansoprazole with no increase in adverse events [40]. It may be possible to tailor the eradication regime offered to individual patients to maximize its efficacy. There are a number of options available to achieve this, which have been examined in the past such as examining bacterial virulence factors and pretesting for antibiotic susceptibility,

but in the last year, some new developments have been made. One of the more interesting targets for this aim lies in understanding the role of the cytochrome P450 2C19 (CYP2C19) genotype in H. pylori eradication. The effect here is exerted via the PPI component of therapy with polymorphisms of the CYP2C19 leading some individuals to metabolize more extensively than others. The studies carried crotamiton out in the last year have mainly involved Chinese patients. One study divided subjects receiving a standard triple-therapy regime with omeprazole into extensive (EM), intermediate (IM), and poor (PM) metabolizers according to their CYP2C19 phenotype: 33% for the EM group, 92% for the IM group, and 100% for PM [41]. CYP2C19 polymorphisms can be overcome somewhat in EM by increasing PPI dose with one study showing significantly higher eradication rates in EM when 40 mg rather than 20 mg of omeprazole is used in a dual-therapy regime [42]. It may also be the case that not all PPIs are the same. In another Chinese study where esomeprazole was used, no significant difference was observed when 40 mg was used as opposed to 20 mg in either rate of eradication or side effects [43]. Similarly, in another study where rabeprazole and lansoprazole were used, a dose-dependent effect was not seen [44].

Additional Supporting Information may be found in the online version of this article.

“
“Hepatocellular carcinoma (HCC) is a common, treatment-resistant malignancy with a complex molecular pathogenesis. Statins are a widely used class of cholesterol-lowering drugs with potential anticancer activity. We reviewed the evidence for a role of statins in primary and secondary chemoprevention of HCC and slowing the course of otherwise GW-572016 cell line incurable primary or recurrent disease. A literature search (key words: Statins, hepatocellular carcinoma) conducted to this end, retrieved 119 references. Here we summarize the history, mechanism of action and cardiovascular use of statins and highlight that statins can affect several pathways implicated in the development of HCC. In vitro and animal studies provide strong evidence for a favorable effect of statins on HCC. However, evidence in humans is conflicting. We discuss in full detail the methodological strengths and pitfalls of published data including three cohort studies suggesting that the use www.selleckchem.com/products/abt-199.html of statins may protect from the development of HCC and of a single trial reporting increased survival in those with advanced HCC randomized to receive statins.

A remarkably hepato-safe class of drugs acting on both hepatocyte and endothelial cells, statins also have potentially beneficial effects in lowering portal hypertension. In conclusion, there is strong experimental evidence that statins are beneficial in chemopreventing and slowing the growth of HCC. However, randomized controlled trials are necessary in order to investigate the role of statins in the chemoprevention of HCC and in slowing the course of otherwise incurable disease in humans. Hepatocellular carcinoma (HCC) is one of the most lethal cancers, and affects many of the world’s populations. Various etiologies have been linked to HCC development, the most prominent of which include hemochromatosis, chronic viral hepatitis due to either B or C infection, excess alcohol consumption and aflatoxin-B1-contaminated food.[1] Virtually all cirrhosis-inducing

conditions can cause HCC, pointing to important interactions with learn more the host micro-environment.[2] Moreover, the number of multifocal disease stemming from non-cirrhotic disease[3] may be expected to increase as a result of the “explosion” of nonalcoholic fatty liver disease (NAFLD) worldwide and of failure to offer surveillance to patients with clinically occult chronic liver disease developed in the setting of the metabolic syndrome. The presently available therapeutic weaponry, which includes radical and palliative options,[4] is not applicable to all patients. Therapeutic failures may result from diagnostic delays, particularly in those with underlying non-cirrhotic liver disease, or recurrent HCC in those with poor liver function.

Serum phytosterol levels might become additional predictive biomarkers for evaluating increased risk of gallstones. A new strategy aiming at inhibiting both hepatic synthesis and intestinal absorption of cholesterol for reducing its biliary output might be envisioned for a genetically defined subgroup of individuals at a high risk for gallstones. Overall, data need to be integrated Selleck PD0325901 with those suggesting that the absorption of intestinal cholesterol indeed plays a role in the pathogenesis of gallstone disease, and that other groups of patients might benefit from drugs (such as ezetimibe) inhibiting

this process.11 Although the ultimate and major sources of biliary cholesterol remain to be established in different populations, a more and more intriguing story about cholesterol cholelithiasis is developing and linking with complex metabolic disturbances and genetics. This will require appropriate preventive and medicinal approaches in the future. “
“M1 activation of hepatic macrophage (MΦ）drives liver inflammation in alcoholic steatohepatitis (ASH). We have previously reported an advanced ASH produced by obesity and

alcohol in a mouse intragastric feeding (iG) model, which is characterized by heightened hepatic MΦ M1 activation with Nos2 upregulation, nitrosative stress, and hepatocyte mitochondria damage, suggesting the central role of M1 Nos2 upregulation in ASH pathogenesis. [Aim] The present study FK228 chemical structure tested the hypothesis that Notch pathway activates Nos2 by direct stimulation of Nos2 transcription,

metabolic reprograming, and generation of mitochondrial R〇S (mtR〇S). [Methods] M1 MΦ was isolated from the liver of iG ASH mice or produced in vitro using Raw264. 7 cells Fenbendazole treated with LPS. Expression of mitochondrial DNA (mtDNA) and nuclear genes involved in mitochondrial metabolism was evaluated by TaqMan qRT-PCR array. Notch intracellular domain (NICD) recruitment to gene promoters was assessed by ChlP; metabolic flux analysis using13C6-glucose; mitochondrial respiration by Seahorse; and mtR〇S by FACS analysis with MitoSox. [Results] Expression of Notch1, its ligand Dll4 and target Hes1, and cellular NICD1 levels are upregulated in M1 MO. NICD1 is enriched at the Nos2 promoter and the promoter activity is suppressed by Notch inhibition with y-secretase inhibitor DAPT. M1 MO has increased glucose uptake, glycolytic flux to TCA cycle, mitochondrial respiration, and mtROS, all of which are blocked or attenuated with DAPT. Pyruvate dehydrogenase (PDH) kinase, which prevents glycolyfic flux to TCA through phosphor-inhibition of PDH, is downregulated. DAPT, glycolytic inhibition with 2-deoxyglucose, and mtROS specific scavenger MitoQ attenuate the expression of Nos2 and other M1 genes.