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Prodigiosin (PG) is a secondary metabolite of bacterial origin that is able to absorb the visible light and plays a role as a photosensitizer in photodynamic therapy (PDT). This in vitro study aimed to investigate the cytotoxicity of PG-mediated PDT against the reference strains of Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of PG were determined. Each strain was then allocated into four groups as follows: G1: control (no treatment), G2: PG-treated groups that received different PG concentrations (1000-1.95 μM), G3: laser-treated group (wavelength: 520 nm, radiation dose: 187 J/cm

Background: The cellular antiviral responses induced by interferons require some cellular protein kinase for its activation. Evidence indicated that a number of Hepatitis C Virus (HCV) proteins can repress double-stranded (ds) RNA-dependent Protein Kinase (PKR) function and help HCV to escape. However, the reports are controversial, some researchers have suggested that a region in Nonstructural 5A (NS5A) gene called Protein Kinase R-Binding Domain (PKR-BD) is associated with HCV sensitivity to the antiviral effects of Interferon (IFN). In addition, the other factor that might be associated with response to PEGylated-IFNα (Peg-IFNα) and Ribavirin (RBV) combination therapy, is IFNL4 genotypes. Objective: The aim of this study was to investigate the association between amino acid (aa) substitutions in the NS5A region and the IFNL4 genotypes in two Single Nucleotide Polymorphism (SNP) (rs8099917. rs12979860) in patients with HCV genotypes 1a and 3a. We also examined their response to combination therapy and the effect of these mutations on the function and structure of PKR-BD. Methods: Eighty-six patients with hepatitis C were recruited and follow-up for 6 months. Several tests, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), viral load, IFNL4 genotyping, and PKR-BD sequencing were performed. Using several well-known and trustworthy bioinformatics tools, sequences were analyzed to define physio-chemical properties, structural features, immune epitopes and protein-protein interaction. Results: Of the 86 patients, 65.1% had high viral load at baseline, 64% had CT genotype for rs12979860 and 57% had GT genotype for rs8099917. Several aa residues changes were found in the PKR-BD region. We could not find any link between mutations in the PKR-BD region and different genotypes of IFNL4 in response to antiviral therapy. Regardless of pI, PKR-BD 1a and 3a showed similar physio-chemical properties, and 2 phosphorylation sites and one glycosylation site were estimated for both PKR-BD 1a and 3a. Trustworthy software were employed in order to predict B-cell epitopes, 3 regions (6-17, 26-32, 34-41) were found for both proteins, indicating a huge potential of PKR-BD protein to induce humoral immune system. Docking analysis determined non-responder sequences in both 1a and 3a genotypes to have higher energy value and are more compatible with PKR. Conclusion: To sum up, our results could not determine any significant relationship between mutations of PKR-BD and genotypes of IFNL4 with other factors; ALT, AST, viral load. However, docking results showed strengthened interaction between PKR-BD and PKR in non-responders that could have a momentous impact on the illness severity.

Background: Arum conophalloides (A. conophalloides) is a wild edible delicate plant, widely used in traditional medicine. Objective: This study aimed to examine the effects of A. conophalloides extracts on biochemical, molecular, and histopathological changes in the rat. Methods: Fifty adult male Sprague-Dawley rats were divided into 5 groups (10 each) as follows: G1 or control, received distilled water; G2 and G3, treated with the aqueous extract at doses of 200 and 400 mg/kg; G4 and G5, treated with the hydroalcoholic extract at doses of 200 and 400 mg/kg. Prior to and at the end of the experiments, the serum levels of biochemistry parameters and the relative expression of miR-122 were assessed. Moreover, the liver and kidney tissues were examined microscopically. Results: Liver and kidney tissues showed normal structure in all groups. There were no significant changes in biochemical indices or the expression of miR-122 in the extract-treated groups at the dose of 200 mg/kg. However, the group that received the aqueous extract at the dose of 400 mg/kg exhibited a significantly lower level of HDL, LDL, ALT, and ALP in comparison to the control. Additionally, miR-122 expression in this group exhibited a 10-fold increase (P=0.009). Conclusion: The serum level of hepatocyte-specific miR-122 will be more helpful in detecting hepatic changes in early stages than ALT and AST activity or histopathological evaluations of liver sections. Our findings highlight the potential hepatotoxicity of A. conophalloides aqueous extract in a rat model.

Background:: HCV Alternate Reading Frame Protein (ARFP) is a frameshift product of HCV-core encoding. Here, we characterized specific anti-ARFP antibodies in Liver Transplant Candidate (LTC) and chronic HCV-infected patients. Methods:: The ARFP gene was cloned and the recombinant protein was purified using Nickel chromatography and confirmed by western blotting. ELISA was developed using recombinant core-1a, core- 1b, ARFP-1a protein, and 99-residue synthetic ARFP 1b peptide. By several Bioinformatics tools, general properties, immunogenic epitopes, and structures of these proteins were obtained. Results:: The seroprevalence of anti-core and anti-ARFP antibodies was 100% in LTC patients, but only 75.2% and 94.3% of chronic patients had evidence of anti-ARFP and anti-core antibodies, respectively. In-silico results demonstrated physicochemical features, antigen properties and potential interactors that could describe progression toward advanced liver disease. Conclusion:: As the first report, the prevalence of anti-ARFP antibodies in LTC patients is of the order of 100% and titer of anti-ARFP antibody was significantly higher in LTC patients compared to chronic individuals, suggesting the possible role of ARFP in the progression toward advanced liver disease. In addition, docking analysis determined several interactor proteins such as prefoldin 2, cathepsin B, vitronectin, and angiotensinogen that have an important role in progression to chronic infection and liver disease development.

Background In vivo cell tracking after transplantation in regenerative medicine remains an unmet challenge and limits current understanding of the wound healing mechanism through cell-based therapies. This study investigated tracking of human Wharton’s jelly stem cells (hWJSCs) seeded onto an acellular dermal matrix (ADM) and labeled with superparamagnetic iron oxide nanoparticles (SPIONs) by magnetic resonance imaging (MRI) in burn injury. Method The hWJSCs were characterized and assessed for growth kinetics. A total of 30 rats were enrolled in three equal groups. Group 1 underwent scald burn injury left without treatment, the group 2 was treated by an ADM that was prepared from cosmetic surgery skin samples and the group 3 received hWJSCs labeled with SPIONs seeded onto an ADM. Tensile strength was evaluated before and after interventions, real time PCR assessed apoptosis, and Prussian blue staining, scanning electron microscopy (SEM) and MRI were used for the tracking of labeled cells. Results The hWJSCs exhibited mesenchymal stem cell properties. Population doubling time was 40.1 hours. SPIONs did not show any toxic effect. The hWJSCs seeded onto an ADM decreased Bax and increased Bcl-2 gene expression. Internalization of SPIONs within hWJSCs was confirmed by Prussian blue staining, SEM and MRI until day 21. There was a significant difference between the Young’s moduli of normal skin and the group receiving hWJSCs seeded onto an ADM. Histological observations and SEM imaging confirmed that MRI is an accurate method to track SPION-labeled hWJSCs in vivo. Conclusions This study showed that SPION labeling coupled with MRI can be used to further understand the fate of stem cells after transplantation in a burn model.

Hepatitis C virus (HCV) is an important causative agent of acute and chronic hepatitis. The non-structural protein 3 (NS3) of HCV retains two enzymatic domains which are essential for the virus life cycle. The serine protease inhibitors have developed to improve the responses of HCV-infected patients that have an effective impact on NS3. Nonetheless, drug-resistant variants are the prominent obstruction toward therapeutic success. Sixty-eight Iranian patients infected with HCV genotypes 1a and 3a and diagnosed with chronic active hepatitis were examined. Plasma viral RNA was used to amplify and sequence the HCV NS3 gene; also, HCV viral load, molecular genotyping, and the ALT test were determined for all samples. The sequencing results were used to be analyzed by several reliable bioinformatics tools to determine the physicochemical properties, B cell epitopes, post-modification changes and secondary/tertiary structures; and evaluate the interactions with four drugs. Our results showed that 45% of patients were 1a genotype, the rest of them belonged to 3a genotype, and 70% of patients had abnormal ALT and AST levels. Several substitutions were observed in codons I52M, S102A, L132I, and S166A in 3a genotype and 40, 153 and 91 in 1a genotype. Interactions between references and sample sequences with available drugs showed that different genotypes or common mutations could not have any striking effect on the energy value of the interaction. This study displayed resistance mutations and genetic polymorphisms of NS3 region that are crucial in determining the efficiency of protease inhibitor class of drugs in Iranian HCV infected patients.

Background Various methods were introduced to overcome the autograft shortage in burn wound care, including cell transplantation and tissue engineering. Aims To evaluate the healing effect of allogenic human Wharton's jelly stem cells (hWJSCs) seeded onto acellular dermal matrix (ADM) in rat burn injuries. Patients and methods Human Wharton's jelly stem cells provided from umbilical cord tissue were characterized before transplantation, and the growth kinetic was determined. Skin samples from cosmetic surgeries were used for preparation of ADM. Forty male Sprague Dawley rats were randomly divided into 4 equal groups. Third-degree burn was induced for all animals by exposing to hot water using a 2 cm ring for 10 seconds. Group 1 was burned rats that did not receive any treatment. After burn injury, the second group received silver sulfadiazine (SSD), the third group was treated just by using ADM, and the fourth group received 2 × 106 hWJSCs seeded onto ADM. The animals were euthanized for histologic evaluation after 7, 14, and 21 days. Results Human Wharton's jelly stem cells were characterized to be spindle shape and positive for osteogenic and adipogenic induction and for mesenchymal markers but lacked hematopoietic markers. Population doubling time (PDT) was 40.1 hours with an increasing growth trend until day 6th. Macro- and microscopically, the healing was mild in ADM group and moderate in ADM + hWJSCs group after 21 days. Conclusion Allogenic hWJSCs seeded onto ADM improved the healing process in burn wounds denoting to their therapeutic and anti-inflammatory effects in burn wounds that can be added to the literature.

Experimental burn can be inflicted by various means, and each method affects the healing processes. To date, several methods have been developed, but their standardization is difficult. We aimed to compare two experimental methods, heated brass bar, and scalding, to provide an in-depth understanding of their limitations and errors. Scald burn is afflicted by pouring 2.5 cc of boiling water (95 °C) into a firm rubber ring (2 cm diameter) on the dorsal surface of a rat skin for 15 s. The other experimental model is performed by bringing a brass bar (2 cm diameter) heated to 95 °C in boiling water in contact with the surface of the skin for 15 s. The clinical course of healing was evaluated macroscopically for 7 days, and then microscopically. The scald burn produced a uniform wound with the same depth of tissue damage without any marked inflammation and hemorrhage. The scab formation and the extent of granulation tissue, as well as re-epithelialization, were the same in all rats and the lesions healed uniformly. Compared with scald, burns of various depths were induced by the heated brass bar and the burn area did not heal uniformly. Widespread hemorrhage and microabscess were common in this group without any sign of scab formation or re-epithelialization. This study highlights the benefits of scald method in comparison with the heated brass bar.

Background & Objective:Perovskia abrotanoidesKarel locally known as Brazambal, is widely used in medical practice to treat various disorders. Burn is a common source of injury and Brazambal ointment has been extensively used in burn wound healing in North of Iran. The purpose of this study was to examine the healing effect of Brazambal ointment in experimental model of burn. In addition, in-vitro healing characteristics and antibacterial activity ofP. abrotanoideswas investigated. Materials & Methods:Scald burn injury was produced by pouring 2.5cc of boiling water (95ºC) on the posterior surface of rat’s neck for 10 seconds. Twenty-eight adult male Sprague Dawley rats were divided into 4 groups (7 rats each) and followed for 7 days. Control group (no treatment); Silver sulfadiazine-treated group; Brazambal ointment-treated group; and vehicle-treated group received the complete ointment without Brazambal part. The effects of Brazambal aqueous extract on fibroblast cells and antibacterial activity againstEscherichia coli,Staphylococcus aureusandPseudomonas aeruginosawere evaluated. Results:Topical application of Brazambal ointment can accelerate wound healing process by initiating re-epithelialization and formation of granulation tissue. Proliferative activity of the aqueous extract on fibroblast cells was observed after 48 h in concentrations of 7.5% and 10% (PP.abrotanoidesKarel extract had no significant antibacterial effect. Conclusion:The presence of hair follicles, re-epithelialization and granulation tissue is suggestive of Brazambal ointment relative effectiveness on experimental scald burn in rats. However, further studies are warranted to reveal the healing mechanisms ofP. abrotanoides. Keywords:Perovskia abrotanoides,Brazambal,Traditional medicine,Burn

Human pegivirus-1 (HPgV-1) is known for its protective role in HIV co-infected individuals. This immunomodulatory effect raised questions concerning the possible role of HPgV-1 infection and the risk of rejection in liver transplanted patients. We aimed to evaluate the possible protective effect of HPgV-1 on graft outcome of liver transplanted patients. A total of 283 patients were recruited. Formalin-fixed paraffin-embedded tissue samples were collected from the explanted liver. HBV-DNA, HCV-RNA, and HPgV-1-RNA were determined using PCR and multiplex RT-PCR assays. The clinical course of patients including the occurrence of acute cellular rejection was compared between HPgV-1-infected vs. uninfected patients. HBV-DNA, HCV-RNA and HPgV-1-RNA were detected in 42.6%, 4.9%, and 7.8% of samples, respectively. None of the HPgV-1-infected patients experienced graft rejection. Group LASSO logistic regression revealed that HPgV-1 infection was the only factor which significantly reduced the odds of graft rejection (OR = 0.5, 95% CI = 0.29-0.89). No significant association was found between the presence of HPgV-1 with HBV and HCV infections. The lack of graft rejection in HPgV-1-infected liver transplanted patients might indicate a possible role of this virus for graft surveillance. Since these are still preliminary findings, prospective studies should further elucidate the role of HPgV-1 in liver transplantation outcomes.

Objective(s): Various therapeutic approaches, including stem-cell-based strategies and tissue engineering, have been proposed for oral ulcerative lesions. We investigated the effects of adipose tissue-derived stem cells (ADSCs) seeded onto the curcumin-loaded collagen scaffold in the mucosal healing of oral ulcers in rats.Materials and Methods: The current experimental study was conducted on 40 male Sprague-Dawley rats. Oral ulcers were created over both sides of buccal mucosa, and the rats were randomly divided into four equal groups: 1) an untreated group (negative control); 2) Teriadent-treated group (positive control); 3) group treated with curcumin-loaded collagen scaffold; and 4) group received the ADSCs (3 × 106 cells) seeded onto the curcumin-loaded collagen scaffold. Rats were sacrificed on 3rd and 7th day after ulceration for histopathological examination as well as measurement of tissue levels of myeloperoxidase (MPO), superoxide dismutase (SOD), and Interleukin-1 beta (IL-1β) activity. Results: Compared with the negative control, the tissue levels of MPO and IL-1β were significantly decreased in all treated groups (p

Objective To investigate hepatotoxicity in Iranian patients with HIV to assess the association between virologic response to HIV treatment and serum alanine aminotransferase (ALT). Methods This study was conducted with 200 control patients, 75 patients with HIV naïve to antiretroviral therapy (ART), and 443 patients who received ARTs with virologic response (≤1000 copies/mL) or virologic treatment failure (>1000 copies/mL). Serum ALT level and HIV viral load were determined in all patients. Results Patient ALT levels were significantly higher than those of control patients (45.1 ± 44.4 IU/L vs 23.8 ± 5.4 IU/L). Compared to patients who were ART-naïve, patients with ART experience had significantly higher ALT levels (38.2 ± 26.2 IU/L vs 46.3 ± 46.7 IU/L), and severe hepatotoxicity was only detected in those with ART experience (8 patients, 1.8%). Mean ALT had no significant difference between virologic response/failure groups. The ALT activity and HIV load had a negative correlation coefficient, but it was not significant. Conclusion Periodic monitoring for the possibility of hepatotoxicity is highly recommended in all patients with HIV, especially in those receiving ART treatment.

We aimed to investigate the association of pretreatment host and/or viral related factors with sustained virological response (SVR) rate in chronic hepatitis C (CHC) infected patients. This cohort study was performed on 200 IFN-naïve Iranian CHC patients who were treated with pegylated interferon-α (PEG-IFN-α) plus ribavirin (RBV). Pretreatment levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting blood sugar (FBS), HCV load and genotype were determined, and the pattern of changes was monitored throughout the course of treatment. The baseline FBS value in the non-responder group was significantly higher than that of the SVR group. The SVR group showed a rapid and continuous decline of ALT/AST activity from the beginning of the treatment, while the ALT level was fluctuating in non-responder and relapse groups. Persistent normalization of transaminases during combination antiviral therapy was significantly associated with SVR rate. Besides, age and FBS levels had the greatest impact on SVR. Minocycline seems to be a safe and effective adjuvant in the management of patients with schizophrenia.

Background: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are the most common markers of liver damage, but serum level interpretation can be complicated. In hepatocytes, microRNA-122 (miR-122) is the most abundant miRs and its high expression in the serum is a characteristic of liver disease. Objective: We aimed to compare the circulatory level of miR-122 in patients with Chronic Hepatitis C (CHC), Hepatitis C Virus (HCV) infected Liver Transplant Candidates (LTC) and healthy controls to determine if miR-122 can be considered as an indicator of chronic and advanced stage of liver disease. Methods: MiR-122 serum level was measured in 170 Interferon-naïve (IFN-naïve) CHC patients, 62 LTC patients, and 132 healthy individuals via TaqMan real-time PCR. Serum levels of miR-122 were normalized to the serum level of Let-7a and miR-221. Also, the ALT and AST levels were measured. Results: ALT and AST activities and the expression of circulatory miR-122 were similar in the CHC and LTC groups, but it had significantly increased compared to healthy individuals (P Conclusion: miR-122 seemed to be more specific for liver diseases in comparison with the routine ALT and AST liver enzymes. Since the lower levels of circulating miR-122 were observed in the LTC group compared to the CHC group, advanced liver damages might reduce the release of miR-122 from the hepatocytes, as a sign of liver function deficiency.

Introduction: Combination of interferon-alpha (IFN-α) and Ribavirin (RBV) drugs is used for treatment of hepatitis C virus (HCV) chronic infection. Various factors play role in the response rate of HCV infected patients to treatment. HCV genotype along with viral load, age, race, obesity, insulin resistance, fibrosis and interleukin 28B gene (IL-28B) polymorphisms are considered the most important ones. In recent years, it has been claimed that some polymorphisms close to IL-28B gene play a significant role in response to combined therapy among which IL-28B polymorphisms have a more important role in sustained virological response (SVR). In this study, frequency of genotypes of rs8099917 polymorphism of interleukin 28B gene in 2 groups of Iranian healthy individuals and HCV infected patients living in Tehran was compared. Materials & Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to compare the frequency of genotypes of rs8099917 polymorphism between 105 healthy individuals and 105 chronic HCV infected patients. The results were analyzed with SPSS version 15 using χ2 test. Findings: The genotype frequency of this polymorphism in the healthy individuals was demonstrated as GG: 1%, GT: 25.7% and TT: 73.3%, while in HCV infected patients, it was shown as GT: 58.1% and TT: 41.9%.. No GG genotype was detected in the patients infected with HCV. Discussion & Conclusion: Our investigation came to the conclusion that a significant difference existed between the 2 groups of Iranian healthy and HCV infected individuals regarding the frequency of rs8099917 genotypes and frequency of favorable TT genotype, because it was higher among the healthy individuals than that of the patients infected with HCV

Interleukin-28B (IL-28B) is suspected to be associated with response to treatment and one of the basic immunological backgrounds in liver transplant candidate (LTC). We aimed to assess whether genotypes of IL-28B can play a role in therapeutic response or advanced stages of liver disease. A total of 364 subjects were genotyped for IL-28B rs12979860 and rs8099917 SNPs using PCR-RFLP assay. Moreover, IL-28 serum level, HCV loads, and genotype were performed. A significant increase was observed in the frequencies of unfavorable rs12979860 genotypes/CT + TT in the chronic hepatitis C (CHC) and LTC groups. In the case of rs8099917, CHC group had a significantly higher frequency of unfavorable genotypes/GT + GG compared to the healthy group. IL-28B serum level was also significantly higher in healthy group compared with the CHC and LTC groups. There were no differences in the distribution of the IL-28B genotypes and haplotypes between responder and non-responder patients. Our results suggest, for the first time, that unfavorable rs12979860 genotypes can be considered one of the important immunological backgrounds in the Iranian LTC population that was confirmed with the lower IL-28 serum level compared to healthy group. Besides, there was a possible association of favorable IL-28B genotypes with lower odds of susceptibility to CHC infection but no support for a positive association between analyzed SNPs and an outcome of therapy. Moreover, non-CT haplotypes may be regarded as a genetic risk factor that can increase the chance of infection with HCV and progression toward end-stage HCV-related liver disease.

Mutations in the core CVR region of hepatitis C virus (HCV) and polymorphisms of interleukin 28B (IL28B) are associated with progression toward liver disease and in response to therapy. In addition, interactions of the core protein with some cell interactors can be related to HCV liver damage. This study aimed to evaluate the effect of core mutations as well as IL28B polymorphism on clinical features, sustained virological response (SVR) in 1a and 3a HCV genotypes amongst Iranian HCV infected patients, and the impact of mutations on core protein properties, antigenic properties, and interactions with HCV inhibitors, using several bioinformatics tools. Seventy-nine Iranian patients infected with HCV genotypes 1a and 3a and diagnosed with chronic active hepatitis were examined. Plasma viral RNA was used to amplify and sequence the HCV Core gene; also, HCV viral load, molecular genotyping, and the liver enzymes were determined for all samples. The sequencing results were analyzed by several reliable bioinformatics tools to determine the physicochemical properties, B cell epitopes, post-modification changes, and secondary/tertiary structures; and evaluate the interactions with 4 drugs by docking method. There were some substitutions in core CVR related to ALT and AST enzymes that can lead to HCV advanced liver disease. The most prevalent mutation for 3a genotypes was a substitution in aa 162 (I to V) while we did not find any mutation in 1a responder group. Polymorphism of the rs8099917 showed that the majority of patients had TG heterozygous and carried CT genotype at the rs12979860. Analysis indicated several phosphorylation sits for core protein as well as two important disulfide bonds. Immunogenic prediction showed that core protein can strongly induce the immune system. Interaction analysis, using the docking method revealed two potential interactors (Vitronectin and SETD2). Generally, mutations in all core CVR regions in all patients showed a relationship between such substitutions and higher liver enzymes that can result in advanced liver disease progression in HCV infected patients. Furthermore, immunoinformatics analysis determined the possible immunodominant regions to be considered in HCV vaccine designs. Furthermore, no association between SVR and IL28B polymorphism was shown. In silico analysis determined modification sites, structures, B-cell epitopes of core protein and interactions with several interactors can lead to persistent HCV infection in the cell and the progress of liver diseases.

Background: The causes of cryptogenic cirrhosis, as one of the most important unresolved issues in the management of liver failure, remains unknown. Hepatitis B virus (HBV) infection with a high impact in Iranian liver graft recipients may have a key role in introducing and developing cryptogenic cirrhosis, especially in the occult form. Therefore, the prevalence of occult HBV infection was evaluated in liver transplant recipients with cryptogenic cirrhosis. Methods: In this cross-sectional study, a total of 127 liver transplant recipients with cryptogenic cirrhosis were recruited. The serum samples of patients were evaluated for immunological HBV infective markers, using enzyme-linked immune sorbent assay (ELISA) methods. Moreover, immunohistochemistry (IHC) was used for detection of HBsAg in liver tissue sections. Collected serums and liver tissue samples were also examined for HBV genomic DNA, using a qualitative polymerase chain reaction (PCR) technique. Results: HBsAg was not found in any studied liver tissue or serum samples. However, HBV genomic DNA was found in the liver tissue and serum samples of 35.4% and 36.2% of the liver transplant patients with cryptogenic cirrhosis, respectively. Occult HBV infection was found in 35.4% of the patients with cryptogenic cirrhosis. Seropositive and seronegative types of occult HBV infection were found in 82.2% and 17.8% of the patients, respectively. Conclusions: Findings of the high prevalence of molecular and immunological markers of HBV infection, especially occult ones, in liver transplanted patients with cryptogenic cirrhosis was re-enforced. These results indicate the important role of occult HBV infection in the pathogenesis of cryptogenic cirrhosis, which needs to be evaluated in the future through comprehensive studies.

Hepatitis C virus (HCV) infection is a serious global health problem and a cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Bioinformatics software has been an effective tool to study the HCV genome as well as core domains. Our research was based on employing several bioinformatics software applications to find important mutations in domain 1 of core protein in Iranian HCV infected samples from 2006 to 2017, and an investigation of general properties, B-cell and T-cell epitopes, modification sites, and structure of domain 1. Domain 1 sequences of 188 HCV samples isolated from 2006 to 2017, Iran, were retrieved from NCBI gene bank. Using several tools, all sequences were analyzed for determination of mutations, physicochemical analysis, B-cell epitopes prediction, T-cell and CTL epitopes prediction, post modification, secondary and tertiary structure prediction. Our analysis determined several mutations in some special positions (70, 90, 91, and 110) that are associated with HCC and hepatocarcinogenesis, efficacy of triple therapy and sustained virological response, and interaction between core and CCR6. Several B-cell, T-cell, and CTL epitopes were recognized. Secondary and tertiary structures were mapped fordomain1 and core proteins. Our study, as a first report, offered inclusive data about frequent mutation in HCV-core gene domain 1 in Iranian sequences that can provide helpful analysis on structure and function of domain 1 of the core gene.

Background & Objective:Toxico-pathological effects of herbal plants have always been a major concern, but little information is provided on the toxico-pathological effects oforiganumon the fetus. Due to ethical rules and regulations, no drug experiment on the human fetus is permitted; hence, the chick embryo model is used as an ideal opportunity to study the adverse effects of drugs. This study aims to assess the histopathological effects of the various doses ofOriganum vulgare(O. vulgare) using the chick embryo model. Materials & Methods:Ross chicken eggs were subjected into four experimental groups (n=7); phosphate buffered saline-injected group andOriganum-injected groups that were treated withO. vulgareleaf-extract at doses of 25, 50, and 100 mg per kg egg-weight, respectively. After injecting the embryos with the extracts, re-incubation was performed and allowed to develop until day 18, when embryos were evaluated for pathological lesions. Results:Treated embryos were normal in theOriganum-injected groups and no defect was noticed on the body features. The microscopic lesions including congestion and edema were made in the brain, liver, kidney, heart, and lung in a dose-dependent manner. Conclusion:It can be concluded thatO. vulgareat a concentration higher than 25 mg per kg is toxic for chick embryo in a dose-dependent manner; therefore, more attention should be given to the toxicity ofO. vulgarein the period of fetal development. Keywords:Chick,Embryo,Fetus,Origanum vulgare,Pathology

Objectives Investigations into the viral causes of end-stage liver disease in liver transplant patients with cryptogenic underlying disease remain of interest. Hepatitis C virus infection, especially in its silent (occult) form, may play a key role in the introduction and development of cryptogenic cirrhosis. We aimed to determine the prevalence of occult hepatitis C virus infection in liver transplant recipients with cryptogenic cirrhosis. Materials and methods In this cross-sectional study, 127 liver transplant recipients confirmed to have cryptogenic cirrhosis were included. Plasma samples of the patients underwent evaluation for hepatitis C virus antibody using the enzyme-linked immunosorbent assay method. Plasma samples and paraffin-embedded liver tissue samples were tested for hepatitis C virus RNA using nested reverse transcriptase-polymerase chain reaction. Results Hepatitis C virus RNA was detected in liver tissue sections of 10 patients (7.9%). However, none of the cryptogenic patients had hepatitis C virus RNA or antibody in their plasma samples. None of the patients had hepatitis C or G virus coinfection, but simultaneous detection of hepatitis B and hepatitis C virus was diagnosed in 4 liver tissue samples. Conclusions A finding of hepatitis C virus RNA in liver tissue samples of transplant recipients presents the historical possibility of occult hepatitis C virus infection as underlying disease in our patients with cryptogenic cirrhosis. Results present an important and determinative role of occult hepatitis C virus infection in the pathogenesis of cryptogenic cirrhosis, which needs further confirmation in additional studies.

Background: Hepatitis C virus (HCV) causes one of the major chronic liver diseases (CLD). Hepatitis C virus-core encoding sequence possesses an overlapping open reading frame (ORF) that expresses a protein called F or core+1. Objectives: The current study aimed at assessing the presence and titer of anti-core+1 antibody (Ab) in 70 Iranian patients infected with HCV-1a, responder and non-responder groups, under combination therapy with pegylated interferon-alpha (PegIFN-alpha) plus ribavirin (RBV) using an enzyme-linked immunosorbent assay (ELISA). Methods: In the current cohort study, HCV-1a core+1 gene was amplified and cloned into vector followed by expressing in Escherichia coli and then, purified by ion exchange chromatography. The antibody titer of patients was evaluated before, during (12, 24, and 48 weeks), and 6 months after the end of therapy (ETR). Results: The seroprevalence of anti-core+1 Ab was 75.7% in pretreatment sera. The combination therapy could induce a decline in the level of anti-core+1 Ab in both groups of responders and non-responders. These changes were significant only in the responders (P = 0.003). The seroprevalence of anti-core+1 Ab had no correlation with the outcome of treatment. Conclusions: According to the current study results, HCV core+1 protein elicit a specific antibody response other than the anti-core protein antibodies. The current study data also suggested that the level of anti-core+1 antibody might be affected by the combination therapyandassociated with sustained virological response (SVR). The data implied that the declining trend of anti-core+1 Abs during the treatment might be an alternative representation of the therapeutic response in Iranian population infected with HCV.

Background/Aims The goal of this study was to review cataract surgery outcomes at three independent surgery treatment centres established by the UK Specialist Hospitals (UKSH) and to compare these outcomes with recognised benchmarks. Methods All patients who underwent cataract surgery at UKSH between July 2005 and March 2013 were included. Complication rates were obtained using annual quality reports, logbooks kept in operating theatres and outpatient departments, and electronic medical records. Refractive outcomes and biometry results between December 2010 and March 2013 were obtained from electronic medical records. Results were compared with previously published benchmarks. Results This study reviewed 20 070 cataract surgeries. UKSH had lower rates of several operative complications compared with the Cataract National Dataset benchmark study. These included choroidal haemorrhage, hyphaema, intraocular lens complications, iris damage from phacoemulsification, nuclear fragment into the vitreous, phacoemulsification wound burn, posterior capsule rupture or vitreous loss or both, vitreous in anterior chamber, and zonular dialysis. UKSH had lower rates of postoperative complications including corneal decompensation, cystoid macular oedema, iris to wound, posterior capsule opacification with yttrium aluminium garnet indicated, raised intraocular pressure, retained soft lens matter, uveitis, vitreous to section, and wound leak. Biometry outcomes at UKSH were significantly better than recently published benchmarks from the National Healthcare Service. Conclusions This is the first large-scale retrospective study of cataract surgery outcomes in the UK independent sector. The results indicate comparable or lower rates for most complications as compared with data collected in a previously published study.

Background: Spontaneous viral clearance occurs in 10% to 40% of individuals after hepatitis C virus infection. Some polymorphisms in IL-28B gene may influence the outcome of HCV infection. The present study aimed at investigating the genotype and allele frequency of IL-28B rs12979860 and rs8099917 SNPs in HCV infected patients in addition to determining their association with disease outcome. Methods: A total of 302 patients with chronic hepatic C infection and 36 individuals whose infection was spontaneously cleared were included in this case-control study. The presences of chronic or spontaneously cleared infection in participants were determined by serologic and molecular methods. Genomic DNA of the participants was extracted using salting out method. IL-28B/IFN-λ3 gene polymorphisms were conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The frequency of CC genotype (P = 0.001) and C allele (P = 0.0007) of IL-28B gene at rs12979860 SNP was significantly higher in participants with spontaneously cleared HCV infection compared to that of those who were chronically infected. In the case of rs8099917 SNP of IL-28B, no correlation was found between frequency of genotype (P = 0.17) or allele (P = 0.12) and HCV infection outcome. The results of haplotype analysis showed the association of CT (P = 0.012) and TT (P = 0.013) haplotypes with spontaneous clearance and chronic infection, respectively. Conclusions: The findings implied that individuals with CC or CT genotype at rs12979860 SNP but rs8099917 SNP was not in association with spontaneous clearance of HCV in an Iranian population with HCV infection.

Background and Objectives: Approximately one-third of hepatitis C virus (HCV) infected patients who complete antiviral therapy with undetectable serum HCV RNA at the end of therapy (ETR), will experience relapse. The reasons for the failure of treatment have not been elucidated. It was showed that HCV RNA can persist and replicate in extra hepatic sites, e.g. in peripheral blood mononuclear cells (PBMCs), but the relevance of its presence with relapse over time is still unknown. Moreover, interferon-gamma (IFN-γ) and IFN-lambdas [IFN-λ1, interleukin-29 (IL-29)], possess potent antiviral activity. We studied if the presence of plus-/minus strand RNA in PBMCs of patients and the serum level of IFN-γ and IL-29, which is the most abundant IFN-lambdas in serum, can be considered as predictive factors in relapse outcomes. Methods: Patients were screened for plus-/minus strand RNA at ETR and after 6 months. Also, we measured the serum level of IFN-γ and IL-29 and compared the result with those who developed a sustained virological response (SVR). Results: Levels of IL-29 and IFN-γ serum were significantly higher in SVR at ETR and 6 months later compared to those of the relapsed patients, but there was no difference between the two groups regarding the presence or absence of plus-/minus HCV strand in PBMCs. Conclusions: Our novel findings showed that the serum level of IL-29 and IFN-γ are predictive of relapse outcomes to HCV treatment, but there was no association between the presence of plus-/minus HCV RNA in PBMCs of patients with an outcome of therapy at ETR and later.