Cannabinoids have recently emerged the anti-hyperalgesic actions

Cannabinoids have recently emerged the anti-hyperalgesic actions in visceral pain, however its molecular mechanisms by which cannabinoid receptors would regulate stress-induced visceral pain and the Y-27632 solubility dmso prolonged visceral hyperalgesia remains unknown. Here, we examined whether cannabinoid receptor activation could prevent the effects of traumatic stress on the development of visceral hyperalgesia via ERK1/2 signaling in a rat model of PTSD, the single-prolonged stress (SPS) model. Methods: The models of post-traumatic stress disorder (PTSD) were created by single-prolonged

stress (SPS) following basic the ovalbumin (OVA) sensitization. Visceral hypersensitivity was measured by grading the behavioral response of rats to phasic colorectal distention (CRD) before

initiation of SPS and at various time points (on days 1, 6, 7, 9, 14) in rats exposed to SPS. Rats were injected with the CB1 receptor agonist WIN55,212–2 (WIN) systemically at different time points following SPS exposure and were tested 1 week later for visceromotor responses (VMR) to phasic CRD and abdominal withdrawal reflex (AWR). To examine ERK1/2 and cannabinoid receptor type 1 (CB1) receptor contributions to visceral hyperalgesia, immunofluorescence staining and Western blotting were performed using spinal cord and colon preparation in parallel experiments. Results: Exposure to SPS TAM Receptor inhibitor enhanced VMR to CRD and impaired AWR. WIN (0.5 mg/kg) administered intraperitoneally 2 or 24 h after SPS prevented the trauma-induced alterations 上海皓元医药股份有限公司 in VMR and AWR. These effects were blocked by co-administration of the CB1 receptor antagonist AM251, suggesting the involvement of CB1 receptors. SPS rats treated with cannabinoid agonist WIN (3 mg/kg, 7 days, i.p.) downregulated p-ERK protein levels, and enhanced

expression of CB1 receptors in dorsal horn of the spinal cord at various time points (on days 7, 14, 21) after SPS when compared with vehicle injection. This effect that was prevented by selective CB1 receptor antagonist AM251. Additionally, Intrathecal administration of ERK1/2 inhibitor (U0126) also prevented the cannabinoid receptor-induced downregulation of p-ERK. Conclusion: These findings suggest that the CB1 receptor-mediated downregulation of ERK1/2 emerged the preventive effects after exposure to a highly stressful event, cannabinoids could serve as a pharmacological treatment of visceral hyperalgesia following exposure to PTSD-like stress. Key Word(s): 1. ERK1/2 signaling; 2. CB1; 3. visceral pain; 4.

Cannabinoids have recently emerged the anti-hyperalgesic actions

Cannabinoids have recently emerged the anti-hyperalgesic actions in visceral pain, however its molecular mechanisms by which cannabinoid receptors would regulate stress-induced visceral pain and the Idasanutlin datasheet prolonged visceral hyperalgesia remains unknown. Here, we examined whether cannabinoid receptor activation could prevent the effects of traumatic stress on the development of visceral hyperalgesia via ERK1/2 signaling in a rat model of PTSD, the single-prolonged stress (SPS) model. Methods: The models of post-traumatic stress disorder (PTSD) were created by single-prolonged

stress (SPS) following basic the ovalbumin (OVA) sensitization. Visceral hypersensitivity was measured by grading the behavioral response of rats to phasic colorectal distention (CRD) before

initiation of SPS and at various time points (on days 1, 6, 7, 9, 14) in rats exposed to SPS. Rats were injected with the CB1 receptor agonist WIN55,212–2 (WIN) systemically at different time points following SPS exposure and were tested 1 week later for visceromotor responses (VMR) to phasic CRD and abdominal withdrawal reflex (AWR). To examine ERK1/2 and cannabinoid receptor type 1 (CB1) receptor contributions to visceral hyperalgesia, immunofluorescence staining and Western blotting were performed using spinal cord and colon preparation in parallel experiments. Results: Exposure to SPS ICG-001 order enhanced VMR to CRD and impaired AWR. WIN (0.5 mg/kg) administered intraperitoneally 2 or 24 h after SPS prevented the trauma-induced alterations MCE公司 in VMR and AWR. These effects were blocked by co-administration of the CB1 receptor antagonist AM251, suggesting the involvement of CB1 receptors. SPS rats treated with cannabinoid agonist WIN (3 mg/kg, 7 days, i.p.) downregulated p-ERK protein levels, and enhanced

expression of CB1 receptors in dorsal horn of the spinal cord at various time points (on days 7, 14, 21) after SPS when compared with vehicle injection. This effect that was prevented by selective CB1 receptor antagonist AM251. Additionally, Intrathecal administration of ERK1/2 inhibitor (U0126) also prevented the cannabinoid receptor-induced downregulation of p-ERK. Conclusion: These findings suggest that the CB1 receptor-mediated downregulation of ERK1/2 emerged the preventive effects after exposure to a highly stressful event, cannabinoids could serve as a pharmacological treatment of visceral hyperalgesia following exposure to PTSD-like stress. Key Word(s): 1. ERK1/2 signaling; 2. CB1; 3. visceral pain; 4.

The presence

The presence buy Decitabine of LAS improved Cu2+ removal by ~20%, and accelerated attainment of Cu2+ retention equilibrium. For the 2- mg · L−1 Cu2+ treatments, retention equilibrium occurred within 2 d and showed maximum Cu2+ removal of 1.83 mg · L−1. In the presence of LAS, the ratio of extracellular bound Cu2+ to intracellular Cu2+ taken up by the cells was lower (1.05–2.26) than corresponding ratios (2.46–7.85) in the absence of LAS. The percentages of extracellular bound Cu2+ to total Cu2+ removal (both bound and taken up by cells) in the presence of LAS ranged from 51.2% to 69.3%, which was lower than their corresponding percentages (71.1%–88.7%) in the absence of LAS. LAS promoted

biologically active MLN0128 price transport of the extracellular bound form of Cu2+ into the cell. In contrast, the addition of LAS did not increase the maximum removal efficiency of Cu2+ (61.4% ± 5.6%) by heat-inactivated cells compared to that of living

cells (59.6% ± 6.0%). These results provide a theoretical foundation for designing bioremediation strategies using FACHB-834 for use in surface waters contaminated by both heavy metals and LAS. “
“Twenty-six strains morphologically identified as Cylindrospermum as well as the closely related taxon Cronbergia siamensis were examined microscopically as well as phylogenetically using sequence data for the 16S rRNA gene and the 16S-23S internal transcribed spacer (ITS) region. Phylogenetic analysis of the 16S rRNA revealed three distinct clades. The clade we designate as Cylindrospermum sensu stricto contained all five of the foundational species, C. maius, C. stagnale, C. licheniforme, C. muscicola, and C. catenatum. In addition to these taxa, three MCE公司 species new to science in this clade were described: C. badium, C. moravicum, and C. pellucidum. Our evidence indicated that Cronbergia is a later synonym of Cylindrospermum. The phylogenetic

position of Cylindrospermum within the Nostocaceae was not clearly resolved in our analyses. Cylindrospermum is unusual among cyanobacterial genera in that the morphological diversity appears to be more evident than sequence divergence. Taxa were clearly separable using morphology, but had very high percent similarity among ribosomal sequences. Given the high diversity we noted in this study, we conclude that there is likely much more diversity remaining to be described in this genus. The genus Cylindrospermum Kütz. ex Bornet et Flahault (1886) is distinguished from other Nostocaceae by the presence of terminal heterocytes with paraheterocytic akinete development, and absence of aerotopes. It is often found associated with damp soils, but also occurs in periodically flooded soils (such as rice paddies) and some species have even been reported to be present in permanent aquatic habitats (Singh et al. 1980, Cronberg 2003). Akinetes in species of Cylindrospermum are large, thick-walled, and often bear spines or other ornamentation on the exospore.

17 The first Denver successes were bolstered

by the openi

17 The first Denver successes were bolstered

by the opening in 1968 of a second clinical liver program by Roy Calne in Cambridge, England,133 following preclinical studies in outbred pigs.21,134 The early trials were described in my 1969 book titled, “Experience Selleckchem ACP-196 in Hepatic Transplantation”,22 based on our first 25 human liver replacements and eight performed elsewhere (four by Calne). Collateral support was provided with the use of the same immunosuppression regimen for the first successful human heart, lung, and pancreas transplantations (Table 5).135-137 However, the promise of the nonrenal procedures, and even of deceased donor kidney transplantation, was unfulfilled for the next 12 years because of immunosuppression-related

morbidity and mortality. Half or more of the liver recipients treated during this time died within the first RG7204 cost post-transplant year. The most encouraging observation was that many patients who survived to this milestone were quietly compiling years of good health thereafter (Fig. 7).64,155 Despite deepening suspicion that progress in the whole field of organ transplantation had permanently stalled, the new French and German liver teams of Henri Bismuth and Rudolf Pichlmayr joined the Denver-Cambridge (England) alliance in the early 1970s, followed later in the decade by the Dutch group of Rudi Krom. Much of the medical-scientific, logistic, and administrative framework of hepatic transplantation that exists today was developed by the five mutually supportive liver centers during the frustrating period between 1969

and 1979. Most of the indications for liver transplant candidacy 上海皓元 were obvious, including inheritable disorders with a definitive biochemical explanation (e.g., Wilson’s disease23). The acid test of liver transplantation ultimately would help elucidate the mechanisms or pathophysiology of less well-understood inborn errors: e.g., the three diseases that were palliated by portacaval shunt (see above). Four patients with alpha-1-antitrypsin deficiency underwent liver transplantation between 1973-1977.138,139 Liver replacement for treatment of glycogen storage disorders,140,141 hyperlipoproteinemia,44, 45 and a growing panoply of other metabolic diseases awaited better immunosuppression. Improvements in therapy were heralded in 1979 by Roy Calne’s report of cyclosporine-based immunosuppression in 34 patients, including two liver recipients.33 The side effects of cyclosporine precluded its use as a single agent. However, when it was substituted for azathioprine in our two-drug or three-drug therapeutic algorithm that included dose-maneuverable prednisone,34 cyclosporine’s full potential was realized. Kidney recipients were the first to be treated, with liver recipients close behind. Eleven of our first 12 liver recipients treated in Colorado with cyclosporine-based immunosuppression during 1979-1980 survived for >1 year.

The cross-sectional imaging patterns of GBC consist of a mass rep

The cross-sectional imaging patterns of GBC consist of a mass replacing the gallbladder (40%–65% of cases) [pattern A], focal or diffuse wall thickening (20%–30%) check details [pattern B]. In pattern C (15%–25%)—as in the present case—GBC is manifested as a polypoid lesion (usually larger than 1 cm in diameter) with

a thickened implantation base. The differential diagnosis should include adenomatous or cholesterol polyps, carcinoid or melanoma metastasis. It has been reported that conventional MRI with associated Magnetic Resonance Angiography (MRA) and MRCP can disclose the disease and simultaneously detect liver or vascular invasion, biliary tract and/or lymph node involvement. Contributed by “
“A 49-year-old male was referred to our hospital for chronic diarrhea and

weight loss. Patient was previously treated for articular rheumatism with immunosuppressive therapy for 7 years without significant benefit. Upon admission, hypochromic microcytic anemia, low serum cholesterol, elevated C-reactive protein and erythrocyte sedimentation rate were observed. Anti-transglutaminase antibodies were normal. Computed tomography (CT) showed multiple intra and retroperitoneal lymphadenopathy suspicious of lymphoma, admixed with some fatty tissue areas. Ultrasonography (US) performed to obtain LY2157299 concentration fine-needle biopsy failed to demonstrate a target lesion, but the retroperitoneum appeared thickened by a diffuse non-homogeneous, hyperechoic fatty-like tissue (Figures 1A and B). Endoscopy showed erythema and erosions of the duodenum. Histology of duodenal biopsies showed modifications suggestive of Whipple’s disease (WD) (Figures 2A and B), confirmed by specific polymerase-chain-reaction. The patient MCE was given twice daily sulfametoxazole/trimetroprim

for one year. The symptoms improved after 3 weeks of treatment and completely disappeared after 3 months. Follow-up CTs showed a progressive reduction of lymphadenopathy. WD is a chronic multi-organ infectious disease caused by Tropheryma whipplei, commonly affecting middle-aged white men. About 1000 cases have been reported. Tropheryma whipplei is a ubiquitous pathogen. The transmission mode is still unclear although faecal-oral way has been suggested. The decreased production of interleukin-12 with reduced release of interferon-gamma by T-cells and defective macrophage activation might represent the predisposing pathogenetic mechanism. Several studies have shown that macrophages accumulating within the lamina propria appear unable to degrade phagocytosed bacteria. WD may interest every organ. Gastrointestinal involvement occurs in 70% of cases with weight loss, diarrhoea and abdominal pain. Extraintestinal manifestations can involve joints, heart, lymphatic system, skin and central nervous system.

1%(5/45), 95% (2/21) and 273% (3/11) at month 24, 36, and 48 N

1%(5/45), 9.5% (2/21) and 27.3% (3/11) at month 24, 36, and 48. Nine patients (20.0%) changed medication dut to myopathy with elevated creatine kinase. Conclusion: Our result shows viral breakthrough and myopathy

were increased in the course of long term use of clevudine. So, clevudine is not suitable as first line treatment of CHB. Key Word(s): 1. Clevudine; 2. Chronic hepatitis B; 3. Viral breakthrough; 4. Myopathy; Presenting Author: KYIKYI THA Additional Authors: CHIRKJENN NG, WENTING TONG, SYAFIQAHABDUL KADAR, WAHYUN LOW, ROSMAWATI MOHAMED Corresponding Author: MAPK Inhibitor Library price KYIKYI THA Affiliations: Monash University Sunway Campus; University of Malaya Objective: The use of complementary and alternative medicine (CAM) is common among patients with chronic hepatitis B (CHB) infection. However, the effectiveness and safety of CAM in the treatment of CHB infection is unclear. This Topoisomerase inhibitor study aimed to explore doctors’ views and experiences on the use of CAM in patients with CHB infection. Methods: We used a qualitative methodology to capture doctors’ views and experiences. The participants were doctors in primary and secondary care, who had experience in managing patients with CHB infection for the past six months. It was conducted in a tertiary hospital located in an urban area in Malaysia between year 2012 and 2013. Two focus groups discussions were conducted (n = 12). Trained

facilitators conducted the focus groups using a topic guide, which was developed based on literature review and expert opinions. Each focus group comprised six participants. The interviews were audio-recorded, transcribed verbatim, checked

and analysed by researchers using a thematic approach. Results: The doctors were aware of a range of CAM for the treatment of CHB infection including herbs, traditional medicine, vitamin supplement and spiritual healing. The attitudes towards CAM varied among the doctors; while some discussed the options, others were either ambivalent or strongly discouraged patients from using CAM. The doctors were aware and concerned about the potential side effects of some of the CAM and the lack of evidence in recommending them in their practice. However, some highlighted that the limitations of western medicine, such as no MCE guarantee for cure, safety, were the reason why patients used CAM. Some doctors also stated that there were lack of clear guidelines and regulations on use of CAM in Malaysia. This has made it challenging for the doctors to advise patients on proper use of CAM. Conclusion: There was a wide variation in the doctors’ views and experiences in managing patients who use CAM. This appears to be due to the lack of evidence on the role of CAM in treating CHB infection. Key Word(s): 1. CAM; 2. Chronic hepatitis B; 3. qualitative study; 4.

Dilatation of the cystic duct appears to be rare but was demonstr

Dilatation of the cystic duct appears to be rare but was demonstrated in the patient illustrated below. A 36-year-old man was investigated because of upper abdominal symptoms including abdominal pain. Blood tests revealed a minor elevation of bilirubin (1.7 mg/dl, 29 μmol/l) and a mild elevation of alanine aminotransferase and gamma-glutamyl transpeptidase. An ultrasound study showed a dilated bile duct, mild dilatation of intrahepatic ducts and minor thickening of the wall of the gallbladder. MRCP revealed a dilated lower bile duct and marked dilatation of the portion of the cystic duct that entered the bile duct (Figure 1).

Other images showed that the junction of the cystic duct and bile duct was widely patent. Tipifarnib in vitro Figure 2 demonstrates a narrow distal bile duct (short arrow), the main pancreatic duct (long arrows) and a long common channel (thick arrow). As the cyst appeared to spare at least some of the common hepatic duct, it was classified as type IB with atypical involvement of a portion of the cystic LDK378 duct. He was treated by cyst excision, cholecystectomy and Roux-en-Y hepaticojejunostomy to correct the extrahepatic obstruction and to minimize the risk of malignant change within the cyst wall. “
“A national viral hepatitis therapy program was launched in

Taiwan in October 2003. This study aimed to assess the impact of the program on reduction of end-stage liver disease burden. Profiles of national registries of households, cancers and death certificates were used to derive incidence and mortality MCE of end-stage liver diseases from 2000 to 2011. The age-gender-adjusted incidence and mortality rates of hepatocellular carcinoma (HCC) and chronic liver diseases and cirrhosis of adults aged 30-69 years were compared before and after launching the program using Poisson regression models. A total of 157,570 and 61,823 patients (15-25% of the eligible for reimbursed treatment) received therapy for chronic hepatitis B and C, respectively,

by 2011. There were 42,526 chronic liver diseases and cirrhosis deaths, 47,392 HCC deaths, and 74,832 incident HCC cases occurred in 140,814,448 person-years from 2000 to 2011. Male gender and elder age were associated with a significantly increased risk of chronic liver diseases and cirrhosis and HCC. The mortality and incidence rates of the end-stage liver diseases decreased continuously from 2000-2003 (before therapy program) through 2004-2007 to 2008-2011 in all age and gender groups. The age-gender-adjusted rate ratio (95% confidence interval, p-value) in 2008-2011 was 0.78 (0.76-0.80, p<0.001) for chronic liver diseases and cirrhosis mortality, 0.76 (0.75-0.78, p<0.005) for HCC mortality, and 0.86 (0.85-0.88, p<0.

Additionally, medication acceptance rates of baseline adherers on

Additionally, medication acceptance rates of baseline adherers on follow up is currently unknown. Aims: 1) To investigate the effects and durability of IBD pharmacist targeted counselling intervention on adherence Selleckchem Lumacaftor rates, necessity and concerns with the primary outcome of increasing medication acceptance. 2) To test whether adherence at baseline changes on long term follow up. Methods: Patients were recruited from the IBD clinic of a Sydney tertiary hospital. Medication Adherence

Rating scale (MARS) questionnaire screened for non-adherence (defined as score ≤16). Beliefs about Medications Questionnaire (BMQ) addressed necessity and concerns (with “medication acceptance” defined as high Necessity >15/ low Concerns score ≤15). Non-adherers were targeted for a structured personalized counselling session with an IBD pharmacist addressing misperceptions, concerns, risk and other queries. Adherers (MARS ≥ 17) were recruited as controls. All patients were followed up with 3-monthly MARS and BMQ questionnaires. Data were analyzed using the Wilcoxon signed rank and Kruskal-Wallis non-parametric statistics and Chi square test. Results: A total of 89 consecutive patients (49% males, median age 37 years, 67% Crohn’s, PS-341 concentration median follow up 12 months, 48% 5-ASA, 66% immunomodulator, 26% biological agent) were prospectively recruited and 21 (23.5%) were non-adherers. For non-adherers, baseline median MARS was 16 increasing

to 19.0 at 3 months (P = 0.02) corresponding to significant increase in medication acceptance rate (P = 0.007). Medication acceptance rates at baseline for non-adherers and adherers were 10.5% and 44.3% respectively (P = 0.008) and at 3 months they were 58.3% and 42.3% respectively (P = 0.358, Table 1). Durability of acceptance was up to 15 months in non-adherers (66.6% P = 0.015) but had declined in baseline adherers

(23.0%, P = 0.095). Non-adherers’ Concern scores significantly decreased from baseline to 3 months (median difference 6, P = 0.033), MCE公司 9 months (median difference 6, P = 0.030) with a durable trend at 15 months (median difference 7, P = 0.08). Although baseline adherers’ median MARS increased from 19 to 20 at 15 months (P = 0.028), 9% had become non-adherent on follow up. Conclusion: Targeted pharmacist counselling intervention on non-adherers effectively increases medication acceptance rates to be equivalent to adherers and was durable to at least 15 months. Medication concerns decreased significantly and were sustained for at least 9 months for non-adherers. However, 9% of adherers became non-adherent at follow up with decreasing medication acceptance rates by 15 months. Medication adherence, therefore, is a dynamic factor that may change over time. Overall, a single targeted session is impactful not only by affecting concerns and adherence in the short term but by initiating a shift in the patient’s attitudes towards their medications. Table 1.

63 Several other medications have been used in the treatment of E

63 Several other medications have been used in the treatment of EoE. Montelukast, a leukotriene inhibitor used in asthma prevention, has been studied in an uncontrolled adult trial but its use was limited because of side effects.72 Mepolizumab, a humanized monoclonal antibody against IL-5, has been shown to effectively reduce esophageal eosinophil counts, but its effect on symptoms was disappointing.73,74 Therefore, given its cost and limited clinical efficacy, Ferroptosis phosphorylation the role of this medication requires further evaluation. As a relatively recently discovered medical condition, EoE is still associated with significant diagnostic, therapeutic and prognostic uncertainties. Controversy

remains as to whether treatment should aim for complete mucosal remission or merely for symptom control. This issue cannot be resolved based on current published knowledge. In this context it will be important to prospectively click here study the natural history of untreated EoE in children and adults. In addition, well-designed head-to-head randomized clinical trials are urgently called for to inform best treatment

guidelines for patients with EoE. Case study 1 A 12-month-old girl (birthweight 3.25 kg) was referred with a history of unsettled behavior, feeding difficulties and failure to thrive. She was breast-fed until 8 months of age, and solids were introduced from 5 months. She initially presented with minor regurgitation after feeds but no overt vomiting. An empirical trial of ranitidine at 2 months of age for suspected GERD did not improve her symptoms. She also had persistent MCE low-grade diarrhea with four to six loose bowel motions daily, but without visible blood. From 4 months of age, her

growth velocity slowed significantly and supplemental soy formula was started by her parents. At the time of first review by a pediatric allergist at 12 months, she was generally well but had ongoing diarrhea. Her weight had fallen to well below the 3rd weight-for-age percentile. On examination, she had a distended abdomen with significant loss of subcutaneous tissue. Bloods tests revealed a mild microcytic anemia. The tissue transglutaminase IgA antibody was negative (normal total serum IgA) while receiving wheat in her diet. SPTs were negative to cow’s milk 0 mm, egg 0 mm, soy 0 mm and wheat 0 mm. The APT was positive for cow’s milk and soy, and negative for egg and wheat. A gastroscopy at the age of 15 months revealed longitudinal furrowing and white plaques in the esophagus; stomach and duodenum were macroscopically normal. Histological examination of esophageal biopsies was in keeping with a diagnosis of EoE, with 42 eosinophils/HPF in the upper, 38/HPF in the middle and 28/HPF in the lower esophagus. Basal cell proliferation occupying more than 50% of the epithelial thickness was demonstrated. Biopsies from stomach and duodenum were normal, thus excluding celiac disease.

αGalCer, alpha-galactosylceramide; α-SMA, alpha-smooth muscle act

αGalCer, alpha-galactosylceramide; α-SMA, alpha-smooth muscle actin; ctgf, connective tissue growth factor; FACS, fluorescent activated cell sorting; FFPE, formalin-fixed paraffin-embedded;

Foxf1, Forkhead box F1; Gli, glioblastoma; Hh, Hedgehog; HSC, hepatic stellate cells; iNKT, invariant natural killer T; LMNC, liver mononuclear cell; MCD, selleck chemicals methionine choline deficient; mmp9, matrix metalloproteinase 9; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; NK, natural killer; NKT, natural killer T; Ptc+/−, patched; Shh, sonic hedgehog; Tgf-β, transforming growth factor beta; Vcam1, vascular cell adhesion molecule 1. C57BL/6 wildtype (WT) (Jackson Laboratories, Bar Harbor, ME), Patched-deficient (Ptc+/−) mice (from R.J. Wechsler-Reya, Duke University, NC), and CD1d-deficient mice (from Z.P. Li, Johns Hopkins University, Baltimore, MD) were fed a methionine-choline deficient (MCD) diet or control chow for 8 weeks. Ptc+/−

mice have only one copy of patched, a Hedgehog (Hh)-pathway repressor. Therefore, they are unable to silence Hh-signaling and exhibit excessive Hh-pathway activity.25 NKT cells are genetically absent in CD1d-deficient mice.26 Formalin-fixed paraffin-embedded (FFPE)-livers were analyzed27 (for detailed protocol and antibodies, see Supporting Information Materials and Methods). Total liver RNA extraction

and messenger RNA (mRNA) quantification by real-time qualitative reverse-transcription polymerase chain reaction (qRT-PCR) were performed as detailed in Supporting Information Angiogenesis inhibitor Materials and Methods.27 Primers are in Supporting Information Table 1. Hydroxylproline content in whole liver specimens was quantified colorimetrically.27 LMNC were isolated from WT mice28, 29 medchemexpress and characterized by fluorescent antibody cell sorting (FACS) as detailed in Supporting Information Materials and Methods. LMNC were cultured in complete NKT media (RPMI 1640, supplemented with IL2 [10 ng/mL; Biolegend] and 10% heat-inactivated fetal bovine serum),28 with or without the NKT cell ligand, alpha-galactosylceramide (αGalCer; 100 ng/mL; Axxora, Cat. no. 306027, CA), for 24 hours. This αGalCer dose elicits maximal iNKT activation.30 Conditioned media were then added to primary murine HSCs for 1 day and RNA was harvested for qRT-PCR. Experiments were performed in duplicate wells and repeated twice. Murine cholangiocyte 603B line (from Yoshiyuki Ueno, Tohoku University, Sendai, Japan, and G. Gores, Mayo Clinic, Rochester, MN),31 rat HSC line 8B (from M. Rojkind, George Washington University, Washington, DC),32 and murine invariant hybridoma cell line DN32 (from Albert Bendelac, University of Chicago, Chicago, IL)33 were cultured according to established protocols.