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In fatty liver disease, systemic homeostasis is perturbed. While pre-clinical models are used to understand its pathogenesis, translating this knowledge to patients is difficult. However, by focusing on the most preserved homeostasis systems between species and models, novel disease dimensions can be unearthed. We interrogated core liver gene co-expression networks in a mouse model of liver cancer following dietary challenge. Immunometabolic modules showed temporal changes under the influence of diet duration and aging. The behaviour of immune network in tumours mirrored their counterparts in non-tumour liver. A high immune response network was associated with a lower tumour burden in mice and humans. This module in mice was enriched for genes related to haematopoietic cell differentiation. Consistently, the bone marrow haematopoietic stem and progenitor cells response was reflective of the liver immune response. Linking haematopoiesis to hepatic homeostasis uncovers a hitherto unexplored dimension of tissue crosstalk that can inform pathogenesis.

Background: Traditional Iranian Medicine (TIM) pays special attention to the prevention of diseases rather than their treatment. The six considerations of maintaining health and prevention from diseases are also apply to the eye in TIM. Objective: This study aims to assess the relationship between essential lifestyle and eye health and preventive factors of ocular diseases in TIM. Methods: In this library-based study, primarily the standpoints of ancient Iranian physicians on the effect of lifestyle concerning the eye health were extracted from 4 sources including Al-Qanun fi at-Teb, Al-Havi fi at-Teb, AL-mujaz fi at-Teb and Akbari’s Teb about food and drinks, climatic conditions and environment, physical activities and rest, sleep and wakefulness, evacuation and retention, and psychological states; Then some of these factors were compared to new literature. Diseases of other organs effective on ocular health were also investigated. The findings were compared with modern medicine in medical literature such as PubMed and Google Scholar databases. Results: Some of the most effective factors on the eye health from the TIM point of view are foods and drinks, sleep, weather conditions, paying attention to evacuation and retention, psychological conditions, physical activities and rest and also stomach health. Conclusion: Correct lifestyle and improving the general health play important role in eye health. Lifestyle modification decrease the risk of developing near-sightedness, age-related macular degeneration, glaucoma, and cataract. More clinical studies should be performed to collaborate the role of all components of the six principles of health maintenance on eye health.

Esmaili et al.1 conducted co-expression network analysis to uncover core homeostatic modules critical to a broad spectrum of liver diseases in mouse and human. Perturbation state of core modules may underlie disease stages across species and serve as therapeutic targets., Esmaili et al. conducted co-expression network analysis to uncover core homeostatic modules critical to a broad spectrum of liver diseases in mouse and human. Perturbation state of core modules may underlie disease stages across species and serve as therapeutic targets.

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) affects a quarter of the adult population. A significant subset of patients are lean, but their underlying pathophysiology is not well understood. Approach and Results: We investigated the role of bile acids (BAs) and the gut microbiome in the pathogenesis of lean NAFLD. BA and fibroblast growth factor (FGF) 19 levels (a surrogate for intestinal farnesoid X receptor [FXR] activity), patatin-like phospholipase domain containing 3 (PNPLA3), and transmembrane 6 superfamily member 2 (TM6SF2) variants, and gut microbiota profiles in lean and nonlean NAFLD were investigated in a cohort of Caucasian patients with biopsy-proven NAFLD (n=538), lean healthy controls (n=30), and experimental murine models. Patients with lean NAFLD had a more favorable metabolic and histological profile compared with those with nonlean NAFLD (P&nbsp

BACKGROUND & AIMS Macrophage activation plays a key pathogenic role in experimental non-alcoholic fatty liver disease (NAFLD) and contributes to the progression of steatohepatitis (NASH) and fibrosis. We studied macrophage activation in human NAFLD by measuring soluble (s)CD163, a specific macrophage activation marker, hypothesizing that sCD163 would be associated with the patients' morphological disease grade. Furthermore, we investigated an association between sCD163 and the apoptosis marker cytokeratin-18 (CK-18) to explore a link between macrophage activation and apoptosis. METHODS sCD163 associations with biochemical and histological measures of NAFLD were investigated in two independent cohorts of 157 Australian and 174 Italian NAFLD patients, with liver biopsies graded for NAFLD severity, steatosis and fibrosis. sCD163 and CK-18 were measured by enzyme-linked immunosorbent assay. RESULTS In both cohorts sCD163 increased in parallel with the patients' morphological disease grading, being independently associated with the Kleiner fibrosis score (P < 0.001). A high sCD163 predicted advanced fibrosis {F ≥ 3; Australian cohort: area under receiver-operating characteristics curve 0.77 [95% confidence interval (CI): 0.76-0.87], Italian cohort: 0.80 (95% CI: 0.72-0.88)}. In both groups, sCD163 was independently associated with CK-18 (P < 0.001). CONCLUSION Soluble CD163 reflecting macrophage activation is associated with morphological features of NAFLD suggesting their involvement in the pathogenesis of NAFLD, NASH and particularly fibrosis. An independent association between sCD163 and cytokeratin-18 suggests that apoptosis may contribute to macrophage activation in NAFLD/NASH.

We evaluated the immune response to neonatal HBV immunization in children of infected parents 10-18 years after primary vaccination. Healthy individuals immunized with an infantile course of three doses of HBV vaccine were tested for persistence of anti-HB surface antibody (HBsAb). Those with an HBsAb level of

Background & Aims: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) is likely due to the interaction between a deranged metabolic milieu and local mediators of hepatic inflammation and fibrosis. We undertook this study to elucidate the interplay between macrophage activation, insulin resistance (IR) in target organs/tissues and hepatic damage. Methods: In 40 non-diabetic patients with biopsy-proven NAFLD we assessed: i) endogenous glucose production (EGP), glucose clearance and indexes of IR in the adipose tissue (Adipo-IR and Lipo-IR) and in the liver (Hep-IR) by tracer infusion ([6,6-2H2]glucose and [2H5]glycerol); ii) macrophage activity (by soluble sCD163) and iii) hepatic expression of CD163 (hCD163). Results: We found that sCD163 levels paralleled both the plasma free fatty acid (FFA) levels and lipolysis from adipose tissue. Consistently, sCD163 significantly correlated with adipose tissue IR (Adipo-IR: r = 0.32, p = 0.042; Lipo-IR: r = 0.39, p = 0.012). At multiple regression analysis, sCD163 levels were associated with FFA levels (r p = 0.35, p = 0.026). In vitro exposure of human monocyte-derived macrophages to palmitate enhanced sCD163 secretion. Conversely, sCD163 did not correlate with EGP or with Hep-IR. In the liver, hCD163 positively correlated with sCD163 (r = 0.58, p = 0.007) and the degree of steatosis (r = 0.34, p = 0.048), but not with EGP or Hep-IR (r = −0.27 and r = 0.11, respectively, p >0.10, both). Conclusions: Our findings suggest a link between deranged metabolism in the adipose tissue and activation of hepatic macrophages in patients with NAFLD, possibly in response to FFA overflow and independent of obesity and diabetes. Conversely, our findings do not support a link between activated hepatic macrophages and glucose metabolism (EGP or Hep-IR). The relationship between adipose tissue IR and hepatic macrophages should be considered to define therapeutic targets for NAFLD. Lay summary: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) is likely due to the interaction between a deranged metabolic milieu and local mediators of hepatic inflammation and fibrosis in the insulin resistant state. This study provides in vivo support for a possible link between deranged metabolism in the adipose tissue and activation of hepatic macrophages in patients with NAFLD, most likely in response to free fatty acid overflow and independent of obesity and diabetes.

Identity and Access Management (IAM) and Single Sign on (SSO) are two security concepts that are related to each other. IAM governs the user access in an organization whereas SSO facilitates the user by authenticating to one centralized application and not having to re-authenticate when trying to access other applications. This paper addresses the different benefits that an IAM and SSO tool can provide to reduce the security risk within an organization. Since, authentication and authorization are one of the major concerns in the cyber security; this paper analyzes common problems that are faced during authentication and authorization. We have also analyzed prior researches that have been done in the IAM and SSO space along with conducting a survey to understand the different issues and benefits of IAM and SSO. From the survey that has been conducted, we have addressed different issues when implementing IAM and SSO solutions along with understanding the architecture, in which these solutions have been deployed into. The surveys conducted have been compared with prior researches done in IAM and SSO space to understand the benefits that the solution provides. The results from the survey have been analyzed to provide the best practices when implementing IAM and SSO solutions along with the benefits provided by the solution.

The aim of this study was to investigate the intra-familial transmission of chronic hepatitis B (CHB) in Golestan province, that has the highest prevalence of CHB in Iran.The Golestan Cohort Study (GCS) is a population-based prospective study of 50045 individuals, 40 years or older, initially set-up to study upper GI cancers in Northern Iran. In 2008, a baseline measurement of hepatitis B surface antigen (HBsAg) on the stored serum of all GCS participants identified 3505 HBsAg+ individuals. In 2011, we assessed HBV serological markers in 2590 initially HBsAg+ individuals and their first-degree relatives including spouses (1454) and children (3934).The median (IQR) age of spouses and children were 52 (12) and 25 (12) years respectively. Out of 5388 family members, 2393 (44.5%) had no HBV markers, indicating susceptibility to infection. Of these, 378 (15.8%) were fully-vaccinated children with no apparent response to primary immunization. HBsAg was positive in 2.2% (n = 33) of spouses and 8.2% (n = 325) of children (overall rate of 6.6%). HBcAb was positive in 761 (52.3%) and 914 (23%) spouses and children, respectively. The rate of spontaneous loss of HBsAg (HBsAg-, HBsAb+ and HbcAb+) was 41.3% and 13.9% in spouses and children, respectively. A higher rate of HBsAg+ children (10.2%) was found in families in which the mother was positive for HBsAg compared with families where the father was positive for HBsAg (6.3%) (P0.001). When both parents were positive for HBsAg, the rate of HBsAg positivity was high (23.5%, P0.001). Despite high virus exposure rates between spouses (52.6 %), the prevalence of HBsAg positivity among them was very low (2.3 %).Sexual and parent-to-child transmission are important routes of CHB spread in this population from northern Iran despite the fact that 24 years have passed since the beginning of hepatitis B vaccination in infants. Low percentage of HBsAg positivity in spouses is related to high HBsAg clearance rate among them.

In this study, silver/silver chloride nanoparticles (Ag@AgCl-NPs) were successfully synthesized using silver nitrate (AgNO3) via an eco-friendly and simple green approach using the seed extract of Conium maculatum (SECM) at room temperature. The biologically synthesized Ag@AgCl-NPs were characterized by UV-vis spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD). Electron microscopic imaging showed that the size of the Ag@AgCl-NPs was about 20 nm, with the particles spherical in shape. Moreover, the crystalline structure of the synthesized nanoparticles was confirmed using the XRD pattern. The potential antibacterial activity of the NPs against standard strains of human pathogens (Gram-positive and negative bacteria) and in vitro anticancer activity against the MCF-7 cell line were investigated. The results demonstrated the ability of the synthesized nanoparticle to kill the cancer cells and inhibit the growth of the human pathogenic and standard strains.

Adiponectin protects against liver fibrosis, but the mechanisms have not been fully elucidated. Here, we showed that adiponectin upregulated inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) and protein expression in hepatic non-parenchymal cells, particularly in hepatic stellate cells (HSCs), and increased nitric oxide (NO2−/NO3−) concentration in HSC-conditioned medium. Adiponectin attenuated HSC proliferation and migration but promoted apoptosis in a NO-dependent manner. More advanced liver fibrosis with decreased iNOS/NO levels was observed in adiponectin knockout mice comparing to wide-type mice when administered with CCI4 while NO donor supplementation rescued the phenotype. Further experiments demonstrated that adiponectin-induced iNOS/NO system activation is mediated through adipoR2-AMPK-JNK/Erk1/2-NF-κB signaling. These data suggest that adiponectin inhibits HSC function, further limiting the development of liver fibrosis at least in part through adiponectin-induced NO release. Therefore, adiponectin-mediated NO signaling may be a novel target for the treatment of liver fibrosis. • Adiponectin activates HSC iNOS/NO and SEC eNOS/NO systems. • Adiponectin inhibits HSC proliferation and migration but promotes its apoptosis. • Adiponectin inhibits CCL4-induced liver fibrosis by modulation of liver iNOS/NO. • Adiponectin stimulates HSC iNOS/NO via adipoR2-AMPK-JNK/ErK1/2-NF-κB pathway.

Adiponectin, one of the most abundant adipose-derived hormones, has variable actions in many tissues and organs. Although principally known for its insulin-sensitizing activity, recent data also highlight its homeostatic function, which is mediated both by direct actions on metabolic cells and indirectly through immunomodulatory effects on immune cells. Here we review the multifaceted immunometabolic actions of adiponectin and attempt to unify some of the contradictory reports on adiponectin function in inflammatory processes. We propose that a holistic understanding of adiponectin function can be garnered only from understanding its actions both on the immune system and on metabolism.

Hepatitis C virus interacts extensively with host factors not only to establish productive infection but also to trigger unique pathological processes. Our recent genome-wide siRNA screen demonstrated that IKKα is a critical host factor for HCV. Here we describe a novel NF-κB-independent and kinase-mediated nuclear function of IKKα in HCV assembly. HCV infection, through its 3’-untranslated region, interacts with DDX3X to activate IKKα, which translocates to the nucleus and induces a CBP/p300-mediated transcriptional program involving SREBPs. This novel innate pathway induces lipogenic genes and enhances core-associated lipid droplet formation to facilitate viral assembly. Chemical inhibitors of IKKα suppress HCV infection and IKKα-induced lipogenesis, offering a proof-of-concept approach for novel HCV therapeutic development. Our results show that HCV commands a novel mechanism to its advantage by exploiting intrinsic innate response and hijacking lipid metabolism, which likely contributes to a high chronicity rate and the pathological hallmark of steatosis in HCV infection.

Adiponectin demonstrates beneficial effects in various metabolic diseases, including diabetes, and in bowel cancer. Recent data also suggest a protective role in colitis. However, the precise molecular mechanisms by which adiponectin and its receptors modulate colitis and the nature of the adaptive immune response in murine models are yet to be elucidated. Adiponectin knock-out mice were orally administered dextran sulfate sodium for 7 days and were compared with wild-type mice. The severity of disease was analyzed histopathologically and through cytokine profiling. HCT116 colonic epithelial cells were employed to analyze the in vitro effects of adiponectin and AdipoR1 interactions in colonic injury following dextran sulfate sodium treatment. Adiponectin knock-out mice receiving dextran sulfate sodium exhibited severe colitis, had greater inflammatory cell infiltration, and an increased presence of activated B cells compared with controls. This was accompanied by an exaggerated proinflammatory cytokine profile and increased STAT3 signaling. Adiponectin knock-out mouse colons had markedly reduced proliferation and increased epithelial apoptosis and cellular stress. In vitro, adiponectin reduced apoptotic, anti-proliferative, and stress signals and restored STAT3 signaling. Following the abrogation of AdipoR1 in vitro, these protective effects of adiponectin were abolished. In summary, adiponectin maintains intestinal homeostasis and protects against murine colitis through interactions with its receptor AdipoR1 and by modulating adaptive immunity.

Summary Objective Early studies on blood donors point to a seroprevalence of approximately 0.25% for hepatitis C virus (HCV) infection in Iran. However, the true prevalence in the general population is unknown. The objective of this study was to determine the prevalence of HCV infection in the general population of Iran. Methods We randomly selected 6583 subjects from three provinces in Iran for inclusion in the study. Subjects were aged between 18 and 65 years. Anti-hepatitis C antibody was tested by a third-generation ELISA test. A recombinant immunoblot assay (RIBA) test was used to confirm the results. Risk factors were recorded and a multivariate analysis was performed. Results A total of 5684 plasma samples were tested. After confirmatory tests, we found 50 cases of HCV. The overall weighted prevalence of anti-HCV was 0.5%. The rate was significantly higher in men (1.0%) than in women (0.1%). In multivariate analysis, male sex, history of intravenous drug abuse, and imprisonment were significantly associated with anti-HCV. Conclusions We found the prevalence of HCV infection in Iran to be higher than previous estimates. It appears that the rate is rising, and in the future, hepatitis C will replace hepatitis B as the most common cause of chronic viral liver disease in Iran.

Although most hepatitis C virus (HCV)-infected individuals develop chronic infection, about 25% of them are able to clear the virus spontaneously without any therapeutic intervention. The aim of the present study was to identify genes associated with spontaneous HCV clearance in a population of Iranian patients. We genotyped 110 single-nucleotide polymorphisms (SNPs) in 59 selected--candidate--genes in a cohort of 107 HCV-infected participants who spontaneously cleared the infection and 176 participants whose infection persisted. Three out of the 110 SNPs were found to be associated with HCV outcome (P-values

The potent chemokine leukotriene B4 (LTB4) is increased in obesity, and is associated with insulin resistance. A recent article shows that inhibition of its receptor LTB4 receptor 1 (Ltb4r1) improves insulin sensitivity in muscle and liver via cytokine-independent mechanisms, and reduces proinflammatory immune cell infiltration in the adipose tissue.

Hepatitis B virus (HBV) infection is the most common cause of end stage liver disease in Iran and in Golestan province. Large-scale population-based prospective cohort studies with long term follow-up are the method of choice to accurately understand the natural course of HBV infection. To date, several studies of HBV epidemiology, natural history, progression to cirrhosis and association with HCC have been reported from other countries. However, few of these are prospective and fewer still are population-based. Moreover, the underlying molecular mechanisms and immunogenetic determinants of the outcome of HBV infection especially in low and middle income countries remains largely unknown. Therefore, the hepatitis B cohort study (HBCS), nested as part of the Golestan Cohort Study (GCS), Golestan, Iran was established in 2008 with the objective to prospectively investigate the natural course of chronic hepatitis B with reference to its epidemiology, viral/host genetic interactions, clinical features and outcome in the Middle East where genotype D HBV accounts for >90% of infections. In 2008, a baseline measurement of HBV surface antigen (HBsAg) was performed on stored serum samples of all GCS participants. A sub-cohort of 3,505 individuals were found to be HBsAg positive and were enrolled in the Golestan HBCS. In 2011, all first degree relatives of HBsAg positive subjects including their children and spouses were invited for HBV serology screening and those who were positive for HBsAg were also included in the Golestan HBCS.

In this study, we investigated long-term mental sequelae of torture in Iran and explored differences between treatment seekers and nontreatment seekers. Thirty-four torture victims suffering from enduring mental sequelae and now living in Germany were examined. According to DSM-III-R, depressive, anxiety, and somatoform disorders were diagnosed with a high degree of comorbidity and with posttraumatic stress disorder (PTSD) being the most frequent diagnosis. Treatment seekers had a higher level of psychopathology, particularly the PTSD symptoms of intrusion and increased arousal, and a poorer knowledge of German. They reported different ways of coping. The differences found between the two groups may reflect more or less successful adaptation to conditions in the host country and contribute to the motivation to seek treatment.

A study of the conductivity type of undoped high quality ZnO thin-films grown on (100) Si substrates by pulsed laser deposition (PLD), is reported. Two groups of samples were prepared at a wide range of growth temperatures between 150 and 350 °C and oxygen overpressure of 5.5×10−6 Torr (low oxygen pressure regime) for one group and 2.5×10−4 Torr (high oxygen pressure regime) for the other group. The electrical properties of the samples were studied by Hall Effect measurements using the four-point van der Pauw method. The measurements were performed using an Ecopia HMS-5000 Hall Effect Measurement System, with fixed magneto-flux density of 0.51T, and injected current that can be controlled between 1nA to 20mA. The system allows for variable temperature readings between 77 and 350K. Standard photolithography was used to prepare a cloverleaf mesa pattern of ZnO for the Hall Effect measurements.

We present the design, fabrication and the first successful demonstration of a bacterial biofilm Surface Acoustic Wave (SAW) sensor. Bacterial biofilms cause severe infections, and are often difficult to remove without invasive surgery. Hence, their detection at an early stage is critical for effective treatment. The detection of biofilm growth is achieved using a high quality zinc oxide (ZnO) piezoelectric thin film which is grown by pulsed laser deposition (PLD). The detection limit of the SAW sensor is approximately 5.3 pico-grams (10−12 g). The resonant frequency shift of the SAW sensor over the biofilm growth period corresponds to in-vitro biofilm growth, demonstrating the first application of a SAW sensor toward real time biofilm sensing. The sensor is biocompatible and the operation frequency is designed to meet the regulations set forth by the Federal Communication Commission (FCC) for implantable applications.

Zinc oxide is a wide band-gap (3.37eV) semiconductor with high exciton binding energy (60meV) and excellent piezoelectric properties, showing promise for UV lasers, optical detection, sensors, and solar cells [1,2]. Epitaxial growth of ZnO on Si is challenging due to lattice mismatch and thermal expansion coefficient differences, but it is important to develop such film growth in order to enhance the functionality of Si and provide optoelectronic and gas sensing capabilities in CMOS based ICs. Furthermore, ZnO grown by most techniques is nominally n-type and p-type films are hard to achieve; hampering the development of p-n junction devices.

We report a conductivity type conversion of ZnO films from n to p-type for films grown on silicon (100) substrates by pulsed laser deposition under low constant oxygen overpressure. Conductivity conversion is attributed to a competition between donor and acceptor-like native defects correlating with growth conditions and surface differences between phosphorus doped n-type and boron doped p-Si substrates. Effects of growth temperature on intrinsic defects including oxygen vacancies, zinc vacancies and hydrogen impurity contamination are discussed. Our results show that the interplay of defect-related centers is critical to the electrical behavior and conductivity type of ZnO grown on Si substrates.