Key Word(s): 1. Hepatocellular ; 2. Carcinoma; 3. Etiology ; 4. Iran; Presenting Author: YIAN ZHANG Additional Authors: TAOTAO LIU, XIZHONG SHEN Corresponding Author: XIZHONG SHEN Affiliations: Zhongshan Hospital affiliated to Fudan University Objective: Neuro-oncological ventral antigen-1(Nova-1) Temsirolimus research buy is a neuron-specific RNA-binding protein, a target antigen in human paraneoplastic opsoclonus-myoclonus ataxia(POMA), always accompanied by malignant tumors. Previous studies reported its expression in breast carcinoma and small cell lung carcinoma. However,

studies on the occurrence of Nova-1 protein in liver cancer have so far been absent. Thus, in this study,we investigated the expression and clinical significance of Nova-1 in hepatocelluar carcinoma (HCC). Methods: We analyzed Nova-1 protein expression in 91 HCC

patients by immunohistochemical staining. The prognostic value of Nova-1 was assessed by using Kaplan-Meier survival estimates and log-rank tests. Results: High expression of intratumoral Nova-1 was associated with poorer survival and increased recurrence (P = 0.01 and 0.022, respectively). Multivariate Cox analysis revealed that intratumoral Nova-1 expression was an independent prognostic factor for OS(HR = 2.120, P = 0.025) and TTR (HR = 1.395, P = 0.002). Moreover, intratumoral Nova-1 could predict HCC early recurrence(HR = 2.163, NVP-AUY922 cell line P = 0.012). Conclusion: Nova-1 may serve as a promising prognostic predictor for poor outcome and high recurrence rate of HCC patients. Key Word(s): 1. Nova-1; 2. HCC; 3. prognosis;

Table 2 Prognostic factors for survival and recurrence Factor   OS     TTR   Early Recurrence find more   Univeriate Multivariate   Univeriate Multivariate   Univeriate Multivariate   P HR(95%CI) P P HR(95%CI) P P HR(95%CI) P Abbreviation: OS, overall survival; TTR, time to recurrence; HR, hazard ratio; CI, confidence interval; AFP, alpha fetoprotein; TNM, tumor-node-metastasis; NS, not significant. Presenting Author: QUN YAN Additional Authors: AIMIN LI, LIJUAN DENG, SIDE LIU Corresponding Author: SIDE LIU Affiliations: Nanfang Hospital, Southern Medical University Objective: Bioartificial liver (BAL) treatment played a significant role in improving survival of patients with liver failure who undergo orthotopic liver transplantation. Human and porcine hepatocytes have been widely used for BAL development. However, the clinical success of BAL has been impeded by the scarcity of human hepatocytes and restrictions on the use of xenogeneic cells. Hepatocellular adenoma (HCA) is an uncommon benign liver tumor. Its monoclonal property may facilitate cell lineage establishment and storage. These properties are attractive for use in BAL development.

, MD, FRCP(C) (Clinical Research Workshop) Nothing to disclose Sherman, Kenneth E., MD, PhD (Early Morning Workshops) Advisory Committees or Review Panels: MedImmune, Bioline, Janssen, Merck, Synteract Grant/Research Support: Merck, Genentech/Roche, Gilead, Anadys, Briston-Myers Squibb, Vertex Sherman, Morris, MD, PhD (SIG Program) Advisory Committees or Review Panels: Merck, Janssen, Roche, Gilead, Celsion, click here Janssen, Eli Lilly, Arqule, Tekmira, Oncozyme,

Nimbus, Rheolysin Speaking and Teaching: Gilead, Bristol Myers Squibb, Bayer Shiffman, Mitchell L., MD (Career Development Workshop, Early Morning Workshops) Advisory Committees or Review Panels: Merck, Gilead, Boehringer- Ingelheim, Bristol-Myers-Squibb, Abbvie, Janssen Consulting: Roche/Genentech, Gen-Probe Grant/Research Support: Merck, Gilead, Boehringer-Ingelheim, Bristol-Myers-Squibb, GSK, Abbvie, Beckman-Coulter,

Achillion, Lumena, Intercept, Novarit, Gen-Probe Speaking and Teaching: Roche/Genentech, Merck, Gilead, GSK, Janssen, Bayer Shrestha, Roshan, MD (SIG Program) Nothing to disclose Silveira, Marina G., MD (Professional Development Workshop) Nothing to disclose Singal, Amit G., MD (Early Morning Workshops, Parallel Session) Speaking and Teaching: Bayer, Onyx Sirlin, Claude B., MD (Parallel

Session) Advisory Committees or Review Panels: Bayer Grant/Research Support: GE, Pfizer, Bayer Speaking Daporinad mw and Teaching: Bayer Slivka, Adam, MD, PhD, FASGE (AASLD/ASGE Endoscopy Course) Consulting: Boston Scientific Grant/Research Support: Mauna Kea Technology Sokol, Ronald J., MD (Early Morning Workshops, Parallel Session) Advisory Committees or Review Panels: Yasoo Health, Inc., Ikaria, Yasoo Health, Inc., Ikaria Consulting: Roche, Roche Grant/Research Support: Lumena Spearman, C. W., MBChB, check details PhD (Global Forum) Nothing to disclose Sterling, Richard K., MD, MSc (ABIM Maintenance of Certification, Career Development Workshop) Advisory Committees or Review Panels: Merck, Vertex, Salix, Bayer, BMS, Abbott, Gilead Grant/Research Support: Merck, Roche/Genentech, Pfizer, Gilead, Boehringer Ingelheim, Bayer, BMS, Abbott Stewart, Charmaine, MD (Parallel Session) Nothing to disclose Strader, Doris B., MD (Parallel Session) Nothing to disclose Stravitz, R. Todd, MD (Early Morning Workshops) Nothing to disclose Strazzabosco, Mario, MD, PhD (Value Based Medicine) Nothing to disclose Subramanian, Ram M., MD (Early Morning Workshops) Nothing to disclose Suchy, Frederick J., MD (AASLD/NASPGHAN Pediatric Symposium) Nothing to disclose Sulkowski, Mark S.

As this occurred in several repeated experiments, the hepatocytes were not investigated further. The movement of procaspase-9 into PLX3397 in vitro and out of the nuclei appeared to occur in an organized manner. Whether this transport depended on the assembly of microtubules was tested by the microtubule-disrupting agent vinblastine. Ten μM vinblastine was added to the cell culture medium 4 hours after the isolation of hepatocytes (Fig. 3B). Its addition prevented the transport of procaspase-9

into cell nuclei. Therefore, procaspase-9 is transported along the microtubules from the cytoplasm to the nuclei. The mitochondrial morphology changed over time in cultured hepatocytes (Fig. 4A). The same types of changes were observed when the mitochondria were labeled by a MitoTracker, fluorescently labeled Tim23 (an integral mitochondrial inner membrane protein) and by fluorescently labeled streptavidin, which specifically labels mitochondria by binding

to biotinylated proteins of mitochondrial matrix.21 Mitochondria were labeled by streptavidin in this study because the strengths of streptavidin fluorescent signals did not vary during the incubation time of primary hepatocytes. Silmitasertib mw Mitochondria appeared circular in liver slices and in freshly isolated cells for up to 8 hours. They appeared dispersed after 24 hours postisolation (Fig. 4A), whereas mitochondria formed longer tubules after 3 days in culture. It seemed that mitochondrial fission predominated immediately after the isolation of primary hepatocytes. As in the case of the nuclear shift of procaspase-9, the fission of mitochondria was reversible too. Despite the

changes in mitochondrial morphology, there was neither Cyt-c leakage from dispersed mitochondria nor was there a decrease in MMP (Fig. 4B). The ratio between the potentials of the energized mitochondria and when MMP was dissipated by FCCP was statistically higher at 1 day of hepatocyte culture compared to immediately after isolation (P = 3 × 10−7, unpaired two-tailed Student’s t test). The difference between the MMPs of hepatocytes immediately after isolation and check details those cultured for 1 day is relatively small and could be due to the presence of some cells that were damaged during isolation in the sample that was assayed immediately thereafter. The change in cellular location of Bax may be another feature of early apoptosis. We localized Bax to the cytoplasm of hepatocytes in rat liver sections (Fig. 5A). In contrast, only minor amounts of it were cytoplasmic, whereas most of it was in the nuclei of the primary hepatocytes cultured for 24 hours. Bax remained predominantly in the nuclei throughout the culturing of primary hepatocytes; it shifted to cytosol and mitochondria whenever apoptosis was induced by STS. The antibody used for labeling of Bax detected a single band of 22 kDa (Fig. 5B). This proves that Bax was labeled specifically.

We analyzed the expression of miR-148a/b and PrPc in GC cell lines. The results showed a negative correlation between the levels of miR-148a/b and PrPc mRNA in these cells. Furthermore, we observed that PrPc mRNA and protein levels were decreased when miR-148a/b were overexpressed by miR-148a/b-lentivirus in MKN28 and SGC7901 cells. The inverse relationship between miR-148a/b and PrPc expression was

further confirmed by in situ hybridization immunohistochemistry in 90 cases of GC, in matched adjacent normal tissues. Luciferase reporter assay showed that the luciferase activity in the Luc-PrPc-transfected cells was significantly decreased compared to the luciferase activity in the mutant and negative control cells (P < 0.05), suggesting that miR-148a/b reduced the luciferase activity of Luc-PrPc but ABT-199 clinical trial had no effect on MDV3100 ic50 Luc-PrPc-mu. Conclusion:  miR-148a/b were significant down-regulated in gastric cancer tissues.

Ectopic expression of miR-148a/b inhibited tumor cell proliferation and metastasis. PrPc may be a target gene of miR-148a/b. Key Word(s): 1. gastric cancer; 2. microRNA; 3. miR-148a/b; 4. PrPc; Presenting Author: ZHANKUN HE Additional Authors: JIANG WANG, QINGXIANG YU, BANGMAO WANG Corresponding Author: BANGMAO WANG Affiliations: Department of Gastroenterology of Tian Jin Medical University General Hospital Objective: Berberine has been shown to possess anti-tumor activity against a wide spectrum of

cancer cells. It inhibits cancer cell proliferation by inducing cell cycle arrest, at G1 and/or G2/M, and apoptosis. In this study, we aimed to determine whether berberine inhibits the cell proliferation and induces cell cycle arrest and apoptosis in human duodenal gastrointestinal stromal tumour selleck inhibitor GIST882 cell line. Methods: The GIST882 cell line were treated with different concentrations of berberine. MTT assay was used to determine the effect of berberine on the viability of these cells. The cell cycle arrest was detected through propidium iodide (PI) staining. The induction of apoptosis was determined via Annexin V-PI staining. Results: Berberine inhibited the viability of GIST882 cells in a dose-and time-dependent manner. The IC50 was found to be 85.54, 52.81, 41.32 μmol/L of berberine at 24 h, 48 h, 72 h, respectly. It also promoted cell cycle arrest at G2/M and induced apoptosis in a dose-and time-dependent manner. Conclusion: Berberine inhibits the cell proliferation and induces cell cycle arrest and apoptosis in human duodenal gastrointestinal stromal tumour GIST882 cell line. Key Word(s): 1. Berberine; 2. GIST882; 3. cell cycle; 4.

Peripheral nerve blocks (PNBs) have been used for the acute and preventive treatment of a variety of primary headache disorders for decades.[1-3] These procedures provide prompt pain relief for many patients with various headache types. Moreover, their analgesic effect typically lasts beyond the duration of anesthesia caused by the nerve blockade, providing some patients with pain relief for several weeks or even months.[4] This prolonged analgesia after peripheral nerve blockade may be due to an effect on central pain modulation.[5] The most widely used target for

PNBs is the greater occipital nerve (GON). Other commonly targeted nerves are the lesser occipital nerve (LON) and several branches of the trigeminal nerve, including the supratrochlear (STN), supraorbital (SON), and auriculotemporal nerves (ATN). PNBs check details are generally safe and well-tolerated procedures that may be performed in the outpatient setting.

A sound knowledge of the anatomy of the different nerves is critical for obtaining good results CP-690550 nmr and for avoiding adverse effects (AEs) such as bleeding or inadvertent systemic injection of the drugs used for nerve blockade. Despite the common use of PNBs by clinicians involved in the care of patients with headache, there has been no standardized approach for the performance of these procedures. A recent survey conducted by the American Headache Society Special Interest Section for PNBs and other Interventional Procedures (AHS-IPS) showed that 69% of responding practitioners used PNBs; however, patterns of use, drug dosages, volumes of injections, and injection schedules varied greatly.[2] To address this issue, members of the AHS-IPS convened, aiming to reach a consensus on the recommended techniques for the performance of PNBs for headaches. In this report, we summarize the results of this effort. This endeavor selleck compound was initiated by a systematic literature review[2] and a survey of the AHS membership[3] by the AHS-IPS that established the need for standardized PNB methodology. Section meetings were convened during the 2010 AHS Scottsdale Headache Symposium

and the 2011 AHS annual scientific meeting in Washington, DC, with a cross-section of the AHS membership who are active with PNBs, featuring formal discussion about each methodological point, and majority rule for consensus. No formal vote was required as an agreement was reached on each point by the AHS-IPS. The manuscript was then drafted and revised by a subcommittee of the AHS-IPS (authors of this manuscript) from July to November 2011. After consultation with the AHS Guidelines Committee and the Board of Directors throughout 2012, the manuscript was determined to be best framed as a narrative review by the AHS-IPS; further edits were implemented, followed by final manuscript submission with full approval from all authors.

During admission, patient developed melena and there was coffee-ground material per NGT, he Cetuximab was referred to gastroenterology service for co-management. His medical history was unremarkable except for a history of previously treated pulmonary tuberculosis in 2012. Physical examination revealed direct tenderness on the epigastric area and there was left lower quadrant rebound tenderness and multiple purpuric rashes on the gluteal area up to the dorso-medial aspect of both lower extremities. The initial leukocyte count was 17000/mm3,

and the C-reactive protein was elevated to more than 16 mg/dL. Urinalysis showed hematuria with trace albuminuria. Serum creatinine and liver function was normal and a plain abdominal film did not show pneumoperitoneum or obstruction. A repeat fecalysis and stool culture was negative for enteric pathogens, and no ova or parasites were found. Results: An selleck inhibitor upper endoscopy showed patchy to linear erythematous areas following the rugal

folds and edematous mucosa from the cardia up to the antral area there was note of stellate to linear ulcers at the second part of the duodenum. Colonoscopy was done which showed patches of erythema, with mucosal and submucosal hemorrhages at the rectum up to the sigmoid area. The skin biopsy of the purpuric lesions showed evolving leukocytoclastic vasculitis compatible with Henoch-Schonlein purpura. Patient was started on IV Hydrocortisone and was eventually shifted to oral prednisone. Abdominal pain improved remarkedly during the course of the steroid therapy. We only maintained the patient on oral proton-pump inhibitor while on prednisone. Conclusion: The American College of Rheumatology has defined four diagnostic criteria, two of which are necessary selleck screening library to distinguish HSP from other forms of vasculitis. These criteria are (a) age of 20 years or younger at onset, (b)

palpable purpura, (c) gastrointestinal bleeding, and (d) biopsy evidence of granulocytes around small arteriolar and venular walls. The clinical presentation of HSP is more severe among adults and tends to be atypical where there is higher rate of severe and atypical gastrointestinal & renal complications. Gastrointestinal pain was the first manifestation in 11% of patients with HSP. Massive GI hemorrhage and grossly bloody or melenic stools are respectively reported in 2% and 30% of the patients 3 Mucosal lesions develop anywhere within the GI tract. Diffuse mucosal redness, small ring-like petechiae and hemorrhagic erosions are characteristic endoscopic findings. As seen in our patient, the small intestine is considered to be the most frequently affected site with the duodenal being the most commonly affected site especially the second part of the duodenum than in the bulb. 3 In most cases, HSP spontaneously disappears without treatment. The use of corticosteroids is controversial and usually reserved for severe systemic manifestations4.

Balloon used for dilatation were Olympus Achalasia Balloon Dilators. All procedures were performed by expert

endoscopists. Telephonic follow up was done and patients response was graded as follows. Excellent response was taken as improvement of dysphagia for both solids and liquids, Good response was taken as improvement of dysphagia for both solids and liquids but still has problems in food intake while poor response was taken as no improvement following balloon dilatation. Time to recurrence of symptoms and complications was also asked. Results: Seventy seven dilatations were performed in 60 patients (mean1.28 ± 0.691). There were 31 males (51.7%) and 29 (48.3%) females. Fostamatinib nmr Male to female ratio was 1.07:1. The age ranged from 13–65 yrs with a mean of 35.48 ± 13.366. The dilatations in the first session ranged from 30–40 mm with a mean of 36 ± 3.884 while the remaining 17 dilatation in the successive sessions ranged from 35–40 with a mean of 38.53 ± 2.35. 25 (41.7%) patients had recurrence of symptoms following balloon dilatation. There were

35(58.33%) patients with excellent response, 19(31.67%) with good response and 6(10%) with poor response after dilatations. There was one (1.7%) case of perforation. 4 patients (6.7%) were referred for surgery after failure to improve after balloon dilatation. Conclusion: Balloon dilation with fluoroscopic guidance is a safe and successful treatment for esophageal achalasia. Key Word(s): 1. Achalasia; 2. pneumatic dilatation Presenting Author: SUZUKI HAJIME Additional Authors: MAEDA SATOSHI, IMAMURA AKIMICHI Corresponding Author: HAJIME SUZUKI Affiliations: Sapporo Kosei selleck chemicals General Hospital, Sapporo Kosei General Hospital Objective: The Japanese Gastric Cancer Association has proposed expanded criteria for the curative endoscopic resection of early gastric cancer. However, it remains controversial

whether endoscopic submucosal dissection (ESD) for submucosal invasive early gastric cancer (SM-EGC) is feasible or not. The aim of our study was to assess the feasibility of ESD for SM-EGC. Methods: We retrospectively collected clinical data of 1060 consecutive patients with gastric lesions who had undergone ESD at our hospital between January 2008 and September 2013. Of these, 150 lesions (14.2%) were classified as MCE SM-EGC by pathological evaluation using the ESD specimen; 72 lesions (47.7%) had submucosal invasion of less than 500 μm (SM1-EGC), and the remaining 78 lesions (52.0%) had invasion of 500 μm or more (SM2-EGC). Results: There were no significant differences in patient age, sex, tumor size, location, and histology or morphological type between patients with SM1-EGC and SM2-EGC. Lymphovascular involvement was found in 9 patients with SM1-EGC (12.5%) and 42 patients with SM2-EGC (53.8%) (p < 0.05). The complete resection rates for SM1-EGC and SM2-EGC were 84.7% and 63.3%, respectively (p < 0.05).

Residual acquisition

is most likely based on automatic coding processes. “
“In the field of dementia research, there are reports of neurodegenerative cases with a focal loss of language, termed primary progressive aphasia (PPA). Currently, this condition has been further sub-classified, with the most recent sub-type dubbed logopenic variant (PPA-LV). As yet, there remains somewhat limited evaluation of the characteristics of this condition, with no studies http://www.selleckchem.com/products/lee011.html providing longitudinal assessment accompanied by post-mortem examination. Moreover, a key characteristic of the PPA-LV case is a deterioration of phonological short-term memory, but again little work has scrutinized the nature of this impairment over time. The current study seeks to redress these oversights and presents detailed longitudinal examination of language and memory function in a case of PPA-LV, with special focus on tests linked to components of phonological short-term memory function. Our findings are then considered with reference to a contemporary model http://www.selleckchem.com/products/Y-27632.html of the neuropsychology of phonological short-term memory. Additionally, post-mortem examinations indicated Alzheimer’s disease type pathology, providing further evidence that the PPA-LV presentation may reflect an atypical presentation of this condition. “
“Visuo-spatial

representations of the alphabet (so-called ‘alphabet forms’) may be as common as other types of sequence–space synaesthesia, but little is known about them or the way they relate to implicit spatial associations in the general population. In the first study, we describe the characteristics of a large sample of alphabet

forms visualized by synaesthetes. They most often run from left to right and have salient features (e.g., bends, breaks) at particular points in the sequence that correspond to chunks in the ‘Alphabet Song’ and at the alphabet mid-point. The Alphabet Song chunking suggests that the visuo-spatial 上海皓元医药股份有限公司 characteristics are derived, at least in part, from those of the verbal sequence learned earlier in life. However, these synaesthetes are no faster at locating points in the sequence (e.g., what comes before/after letter X?) than controls. They tend to be more spatially consistent (measured by eye tracking) and letters can act as attentional cues to left/right space in synaesthetes with alphabet forms (measured by saccades), but not in non-synaesthetes. This attentional cueing suggests dissociation between numbers (which reliably act as attentional cues in synaesthetes and non-synaesthetes) and letters (which act as attentional cues in synaesthetes only). “
“About 50% of neglect patients show ipsilesional target re-exploration on neglect tasks and in daily life. The present study examines whether omissions and revisitings are due to disengagement failure from visible stimuli on the ipsilesional side.

However, the mechanisms by which caspase-1 affects tumor cancer progression remain incompletely understood. We speculate that hypoxia promotes the caspase-1 activation and maturation of IL-1β and -18, thus contributing to invasion and metastasis. Inflammation can promote tumorigenesis. Robust epidemiological data support the role of inflammation induced by chronic hepatitis B or C viral (HBV/HCV) selleck chemicals llc infections and alcohol abuse as key players in HCC development. Lymphotoxin, the proinflammatory and homeostatic cytokine, is induced by HBV or HCV infection and can promote HCC development.31

Similarly, HMGB1 can be secreted in response to HBC or HCV infection and can contribute to the pathogenesis of these infections.32, 33 Additionally, HMGB1 may be involved in the initial phases of tumorigenesis associated with these viral infections. Indeed, activation of the HMGB1 receptor, RAGE, significantly affects tumorigenesis and hepatic tumor growth.34 Studies have shown that, when HMGB1 is overexpressed, the oncoproteins, Cyclin D and E, which regulate cell proliferation, are overexpressed, whereas selleck compound tumor-suppressor protein p53 is repressed.35 Overexpression of HMGB1 is also associated with tumor progression, including invasion and metastasis13; however, the mechanism is still not fully understood. We hypothesized that during hypoxia, the release of HMGB1 may promote caspase-1 activation and may thus contribute

to invasion and metastasis of liver cancer. Our results demonstrate that inhibiting HMGB1 release or blocking its effects inhibits the activation of caspase-1 in hypoxia. In normoxia, rhHMGB1 can induce caspase-1 activation. This confirms that released HMGB1 from HCC cells can induce caspase-1 activation in both normoxia and hypoxia. Using Transwell experiments, we confirmed that hypoxia promotes liver cancer cell migration and invasion in vitro. Therefore, we wished to study what role HMGB1 plays in hypoxia-induced invasion. We found that HMGB1-induced

MCE caspase-1 activation promoted invasion in hypoxia. Conversely, knockdown of endogenous HMGB1, specifically using shRNA, significantly reduced the invasiveness of HCC cells, indicating that HMGB1 is closely involved in HCC invasion. Furthermore, an in vivo murine model of HCC lung metastases also confirmed that HMGB1 is associated with tumor invasion and metastasis. Taken together, our data demonstrate that HMGB1 plays a pivotal role in HCC invasion and metastasis by way of enhancing invasiveness and activating caspase-1, with the subsequent production of multiple mediators. These findings support the notion that HMGB1 may serve as a suitable target for the development of novel anticancer agents. Expert technical assistance from X. Liao, L. Shao, and J. Chen is appreciated. The authors thank J. Evankovich, L. Zhang, G. Nace, and J. Klune for their valuable advice and discussion.

9 The currently accepted model stipulates Vemurafenib that alcohol-induced enhancement of gut permeability to bacterial LPS/endotoxin increases the translocation of endotoxin to the liver that activates Kupffer cells after binding to Toll-like receptor 4 (TLR4).8, 10 Alcohol also sensitizes Kupffer cells to LPS by increasing

oxidative stress and primes Kupffer cells to respond to LPS by up-regulating a number of proinflammatory mediators, including cytokines and chemokines, as well as their cognate receptors.11, 12 Among the panel of secreted cytokines, tumor necrosis factor-alpha (TNF-α) is considered as a major mediator of alcohol-induced liver injury, as shown in a number of clinical studies,8, 13 and on the basis of experimental data demonstrating the substantial reduction of hepatic steatosis, as well as liver inflammation and injury, in TNF-R1 deficient mice and in rats treated with TNF-α antibodies.14, 15 These findings have prompted an evaluation of the effect of TNF-α antibody treatment in patients with severe alcoholic hepatitis, an entity associated with elevated buy Sirolimus short-term mortality. Unfortunately, direct blockade of TNF-α has proved deleterious, owing to a high rate of infectious events in these patients.16 Therefore, other strategies need to be envisioned, and interventional tools able to favor the anti-inflammatory M2 phenotype

in the liver warrant consideration as potential protective agents for the management of alcohol-induced liver injury. Cannabinoid CB2 receptors are G-protein-coupled receptors predominantly expressed by cells of the immune system, including macrophages. These receptors are constituent elements of an endocannabinoid system with pleiotropic effects that also comprise CB1 receptors, highly lipophilic ligands known as endocannabinoids, and mediators responsible for their synthesis, metabolism, and catabolism.17, 18 A number of studies have demonstrated that CB2 receptors display potent

anti-inflammatory 上海皓元医药股份有限公司 properties, although proinflammatory effects have occasionally been described.17, 19, 20 Thus, CB2 receptors reduce inflammation in models of atherosclerosis21 and in a variety of neuroinflammatory disorders, including multiple sclerosis, Alzheimer’s disease, or amyotrophic lateral sclerosis.22 In addition, in vitro studies have shown that CB2-receptor activation impairs several macrophage functions, such as oxidized low-density lipoprotein (oxLDL)-induced inflammatory response, oxidative stress, migration, and antigen processing.22 In the liver, recent data indicate that CB2 receptors are induced after acute or chronic injury, both in Kupffer cells and in liver fibrogenic cells.23-25 Remarkably, endogenous activation of these receptors has been shown to limit liver injury in several instances.