Resveratrol suppresses hyperglycemia-induced activation of NF-κB and AP-1 via c-Jun and RelA gene regulation.

Background: Resveratrol (RSV) provides several important biological functions in wide variety of cells. In this study, we investigated the molecular mechanisms underlying anti-inflammatory effect of RSV on HepG2 cells by assessing the gene expression of RelA and c-Jun- subunits of NF-κB and AP-1 transcription factors. Methods: HepG2 cells were settled in a serum- free medium with high concentrations of glucose (30 mM) and insulin (1 µM) overnight and were then incubated with RSV (5, 10, and 20 µM) for 24 and 48 hours. Real time quantitative polymerase chain reaction (qRT-PCR) was used to determine RelA and c-Jun expression. Results: RSV diminished hyperglycemia/hyperinsulinemia stimulated expression of c-Jun dose- dependently after 24 and 48 hours (p<0.05). In addition, RelA gene expression was decreased dose-dependently in all RSV doses after 48-hour incubation (p<0.05). Our results indicated that RSV may reduce NF-κB and AP-1 activity via RelA and c-Jun gene regulation. Conclusion: The findings of the present study demonstrated that RSV may be considered as a preventative and therapeutic agent for antagonizing inflammation in Hepatocellular carcinoma (HCC).

Metal-based biologically active azoles and ß-lactams derived from sulfa drugs.

Metal complexes of Schiff bases derived from sulfamethoxazole (SMZ) and sulfathiazole (STZ), converted to their ß-lactam derivatives have been synthesized and experimentally characterized by elemental analysis, spectral (IR, (1)H NMR, (13)C NMR, and EI-mass), molar conductance measurements and thermal analysis techniques. The structural and electronic properties of the studied molecules were investigated theoretically by performing density functional theory (DFT) to access reliable results to the experimental values. The spectral and thermal analysis reveals that the Schiff bases act as bidentate ligands via the coordination of azomethine nitrogen to metal ions as well as the proton displacement from the phenolic group through the metal ions; therefore, Cu complexes can attain the square planner arrangement and Zn complexes have a distorted tetrahedral structure. The thermogravimetric (TG/DTG) analyses confirm high stability for all complexes followed by thermal decomposition in different steps. In addition, the antibacterial activities of synthesized compounds have been screened in vitro against various pathogenic bacterial species. Inspection of the results revealed that all newly synthesized complexes individually exhibit varying degrees of inhibitory effects on the growth of the tested bacterial species, therefore, they may be considered as drug candidates for bacterial pathogens. The free Schiff base ligands (1-2) exhibited a broad spectrum antibacterial activity against Gram negative Escherichia coli, Pseudomonas aeruginosa, and Proteus spp., and Gram positive Staphylococcus aureus bacterial strains. The results also indicated that the ß-lactam derivatives (3-4) have high antibacterial activities on Gram positive bacteria as well as the metal complexes (5-8), particularly Zn complexes, have a significant activity against all Gram negative bacterial strains. It has been shown that the metal complexes have significantly higher activity than corresponding ligands due to chelation process which reduces the polarity of metal ion by coordinating with ligands.

Invasive Fungal Infections With Good Survival Following Liver Transplant: A Single-Center Experience From a Developing Country.

OBJECTIVES: Invasive fungal infection following liver transplant is considered as one of the important factors influencing morbidity and mortality among liver transplant recipients. The aim of the present study was to describe the prevalence of invasive fungal infections and their predisposing factors in a singlecenter cohort of patients who received liver transplant. MATERIALS AND METHODS: For this study, 250 adult patients undergoing orthotopic liver transplant between March 2010 and March 2015 were enrolled. All patients were followed prospectively for infections. RESULTS: The diagnosis of invasive fungal infection was made in 15 patients (6%). One patient had 2 episodes of fungal infection, and reoperation was performed for 3 patients. Invasive aspergillosis developed in 8 patients (53.3%),followed by Candida species infection in 3 patients (20%) and cryptococcosis in 2 patients (13.3%).The main predisposing factors were renal failure (12/15) and positive history of rejection (11/15). Other risk factors for development of invasive fungal infections were choledochojejunostomy in 3 patients (20%), bile leaks in 3 patients (20%), and pretransplant steroid use in 2 patients (11.8%). Two patients (13.3%) died due to invasive fungal infections. CONCLUSIONS: In this single-center series of liver transplant recipients, the incidence of invasive fungal infections was relatively low, probably due to the universal prophylaxis with fluconazole and limited use of the broad-spectrum antibiotics. Early diagnosis and treatment of invasive fungal infections could lead to a better prognosis for liver transplant recipients with invasive fungal infections.

Conflict of Interest: Are Iranian Breast Cancer Specialists Prone to it?

INTRODUCTION: Giving gifts is a common way to promote and encourage the use of products of trading companies and increase the patient referrals to diagnostic centers. The present study aimed to assess the practice of physicians of different (sub) specialties/educational levels engaged in breast cancer management in some conflict of interest (COI) situations in their relation with pharmaceutical companies and paraclinical centers. METHODS: A self-administered online questionnaire including questions on demographic and professional information as well as the attitude of physicians toward COI by answering the questions in three different practical scenarios was developed. Respondents were asked to answer each question by selecting one of the five options: strongly agree, agree, undecided/neutral, disagree, and strongly disagree in their own practices as well as the same questions asking the same subject for what they think of the other physicians. Descriptive statistical analysis was used to report qualitative and quantitative variables. RESULT: The response rate was 66.24%. In general, physicians considered their performance better than that of other physicians in the situations asked. More than 90% stated that they would participate in the sponsorship congress for introducing new drugs. One fifth of the physicians stated that they would accept the 30% financial proposition for the referral of every single patient to other clinics. More than half of the physicians stated that they had considered the risks resulted from the COI for referring patients to private radiobiological centers. CONCLUSION: This study indicated that physicians in the field of breast cancer were at the risk of COI. Even within the medical field, there is not sufficient trust in the proper functioning of doctors in dealing with COI situations.
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Retrospective Review of Complications of Liver Hydatid Cyst Surgery with Emphasis on Outcomes of Omentoplasty.

BACKGROUND: The outcome and complications of liver hydatid cyst surgeries with new and old techniques are not well determined. We intended to present the results of operations done for patients with hepatic hydatid cyst in an endemic area. METHODS: Data of 112 patients referred and operated for liver hydatid cyst, in Imam Khomeini Hospital complex, Tehran, Iran, from 2015 to 2018, were collected including demographic characteristics, operation parameters and complication related statistics. The variables were presented for different surgical methods including operations with and without omentoplasty. RESULTS: Patients aged 39. 3 ± 13. 9 yr (70 females; 63. 5%). Most frequent clinical complaint was vague abdominal pain (n=45; 40. 2%). The most prevalent comorbidity was hypertension (18; 16.0%). Conservative methods were chosen more frequently including omentoplasty (44; 39. 3%), cyst drainage (27; 24. 1%), cyst resection (19; 17%) and marsupialization (3; 2. 7%). Overall, 56 patients (50%) were operated with omentoplasty as the single method or in combination with segmentectomy. Complications occurred less in patients operated with omentoplasty (41. 1 vs. 23. 2%; P=0. 043); particularly, biloma was more frequent in surgeries without omentoplasty (7. 1 vs 0. 0%; P=0. 042). Persistence and recurrence rates were 12. 5% and 3. 6% with relative predilection in, respectively, segmentectomy and lobectomy surgical methods compared to Omentoplasty. No mortality was recorded. CONCLUSIONS: In our case series of hepatic hydatid cyst patients, omentoplasty was safe with less complication and similar long-term recurrence rate.

Comparison of Coagulation Conditions in Patients With Liver Cirrhosis Due to Primary Sclerosing Cholangitis and Nonbiliary Causes of Cirrhosis Before Orthotopic Liver Transplant.

OBJECTIVES: Orthotopic liver transplant can be accompanied by an obscure bleeding pattern in patients with severe hepatic malfunction. In the present study, coagulation conditions of patients with cirrhosis of the liver due to primary sclerosing cholangitis and nonbiliary causes of cirrhosis were compared using rotational thromboelastometry assays obtained before orthotopic liver transplant. MATERIALS AND METHODS: This case control study analyzed patients who were candidates for orthotopic liver transplant from 2010 to 2016. Eighty patients with cirrhosis of the liver (40 patients with primary sclerosing cholangitis and 40 with nonbiliary causes of cirrhosis) were randomly selected and enrolled into the study. Patients received rotational thromboelastometry assays under anesthesia just before the start of the operation, and results were compared between the 2 patient groups. RESULTS: Of 80 patients, 52 were men and 28 were women. In the assays, we found that maximum amplitudes in 10 and in 20 minutes and maximum clot firmness parameters were higher in patients with primary sclerosing cholangitis. The alpha angle and clot formation time were different in the intrinsic and extrinsic assay panels. In the intrinsic assay, we found clotting time to be shorter (P < .05). The average of all parameters in all 3 assays (intrinsic, extrinsic, and fibrinogen contribution) was lower in patients with nonbiliary causes of cirrhosis than in those with primary sclerosing cholangitis. CONCLUSIONS: In contrast with previous studies that found that patients with primary sclerosing cholangitis are hypercoagulable, our study observed that they have normal coagulable results. Furthermore, we found that, although mean coagulation indexes in patients with primary sclerosing cholangitis were within normal ranges, in patients with nonbiliary causes of cirrhosis, these indexes were generally lower.

The utility of early post-liver transplantation model for end-stage liver disease score in prediction of long-term mortality.

BACKGROUND: Little is known about the prognostic ability of post-liver transplantation (LT) model for end-stage liver disease (MELD) score measurement in assessing long-term outcomes. The aim of the present study was to investigate this possible relationship. METHODS: In this retrospective cohort study, the medical records of LT recipients operated under a LT program were reviewed. The accuracy of post-operation MELD score for predicting mortality was evaluated based on receiver operating characteristic (ROC) curves. Univariate and Cox proportional hazard regression models were used to assess the risk factors associated with mortality. RESULTS: Eight hundred twenty-six consecutive LT recipients were included in the study. The areas under the ROC curve on postoperative days (POD) 5 and 9 for predicting 1-year mortality were 0.712 (95% confidence interval [CI] 0.614-0.811) and 0.682 (95%CI 0.571-0.798), respectively. A cutoff point of 14.5 was obtained for MELD score on POD5 that significantly differentiated between survivors and non-survivors with a sensitivity of 69.8% (95%CI 50.7-83.1) and a specificity of 57.2% (95%CI 50.6-63.6). In the Cox multivariate analysis, factors including MELD score on POD5 (hazard ratio [HR] 1.83, 95%CI 1.07-3.12; P=0.026), pre-transplant MELD (HR 1.064, 95%CI 1.025-1.104; P=0.001) and operation duration (min) (HR 1.004, 95%CI 1.003-1.006; P=0.013) were identified as independent risk factors for predicting overall survival. CONCLUSION: The immediate postoperative MELD scores after LT may be of value in predicting mortality and could be used as a tool for postoperative risk assessment of patients.

NAFLD Prevalence in a Young Cadaveric Organ Donor Population.

BACKGROUND: Liver transplantation is a critical survival point for patients with end stage liver diseases. It can dramatically increase patients' survival if the donor liver is intact. One aspect of liver health is absence of steatosis. Nonalcoholic Steato Hepatitis (NASH) and Nonalcoholic Fatty Liver Disease (NAFLD) are increasing among young adults and patients living with chronic liver diseases. OBJECTIVES: In this study, we determined the prevalence of NALFD in livers of brain-dead donors in Imam-Khomeini hospital Complex, Tehran, Iran. We assumed that the calculated prevalence would represent NAFLD prevalence in Iranian population in the age range of 20-60 years. MATERIALS AND METHODS: All eligible brain dead liver transplant donors were enrolled in the survey from March 21, 2011 to March 21, 2013 in Imam-Khomeini hospital Complex. Eligible participants were donors aged 20 to 60 years without any obvious history of liver disease. Liver needle biopsy was performed at the end of the transplant operation; time zero biopsy. We calculated the prevalence of NAFLD among brain-dead donors. Moreover, the frequency of NASH was calculated based on the NAS (NAFLD Activity Score). RESULTS: Among 116 cases, two were diagnosed as probable NASH. There was a significant association between NAFLD and male gender (P = 0.04). Moreover, we found a higher steatosis level in male gender. There was a significant association between NAFLD and BMI (P = 0.05). Those with BMI more than 27 had severe steatosis. CONCLUSIONS: Our comprehensive literature review showed that our study was the first investigation in Iran and the region, which determined the prevalence of NAFLD based on tissue diagnosis. We believe that the prevalence of NAFLD/NASH in our donors can represent the overall prevalence in this age group in Iran.