Anticancer properties of red beetroot hydro-alcoholic extract and its main constituent; betanin on colorectal cancer cell lines.

Colorectal cancer (CRC) is the third most common type of cancer worldwide. Red beetroot (Beta vulgaris) contains Betanin as its major betacyanin, possessing wide proapoptotic effects. This study aimed to investigate the anticancer and pro-papoptotic effects of beetroot hydro-alcoholic extract (BHE) and betanin, on colorectal cancer cell lines. BHE and betanin were used to treat Caco-2 and HT-29 colorectal cancer cells. MTT assay, DAPI staining, and FACS-flow cytometry tests were used to determine the half-maximal inhibitory concentration (IC50) and apoptosis-inducing evaluations. Intended genes were assessed by real-time polymerase chain reaction (RT-PCR). The IC50 for HT-29 and Caco-2 cell lines were 92 µg/mL, 107 µg/mL for BHE, and 64 µg/mL, 90 µg/mL for betanin at 48 h, respectively. BHE and betanin significantly inhibited the growth of both cancer cell lines time and dose-dependently. DAPI staining and flow cytometry results revealed significant apoptosis symptoms in treated cancerous cell lines. The expression level of proapoptotic genes (BAD, Caspase-3, Caspase-8, Caspase-9, and Fas-R) in treated HT-29 and Caco-2 cells was higher than in untreated and normal cells. In contrast, the anti-apoptotic gene (Bcl-2) was significantly downregulated. BHE and betanin effectively inhibited cancer cell proliferation and induced apoptosis via the modification of effective genes.

Prevalence and Predicting Risk Factors of Polypharmacy in Azar Cohort Population.

Background: As polypharmacy has some medically negative impacts, it has become a challenging issue for public health and affected people. Therefore, we decided to investigate the prevalence of polypharmacy and its predicting risk factors in the Azar cohort population. Methods: In this cross-sectional population-based cohort study, the prevalence of polypharmacy was evaluated in 15,001 subjects who participated in the Azar cohort study. We measured demographic characteristics (age, gender, socioeconomic status, smoking status, marital status, and education level), physical activity level, body mass index (BMI), blood pressure, multimorbidity (coexistence of two or more chronic diseases (CDs)), and polypharmacy status (a daily intake of five or more medicines for a minimum of 90 days). Results: Based on our results, 9.51% of the population had polypharmacy. The five most prescribed medications were drugs acting on the cardiovascular system (19.9%), central nervous system (16.7%), endocrine system (13.3%), NSAIDs (11.5%), and drugs used for musculoskeletal and joint diseases (11.4%). Being female, illiterate, and having the lowest tertile of physical activity level significantly increased the risk of polypharmacy. The risk of polypharmacy was 49.36 times higher in patients with four or more CDs than in those without. Conclusions: Our study emphasized the importance of routine monitoring to evaluate polypharmacy among those aged 35 to 59 and the elderly. Physicians should carefully assess drug suitability, especially in multimorbid and obese patients, to prevent excessive polypharmacy and its potentially negative impacts.

Prevalence, awareness, treatment, and control of hypertension based on ACC/AHA versus JNC7 guidelines in the PERSIAN cohort study.

In this cross-sectional population-based study, we used the baseline data of the Prospective Epidemiologic Research Studies in IrAN cohort study collected in Iran from 2014 to 2020. The main outcomes were the prevalence of hypertension and proportion of awareness, treatment, and control based on the 2017 ACC/AHA guideline compared to the seventh report of the Joint National Committee (JNC7). Of the total of 163,770 participants, aged 35-70 years, 55.2% were female. The sex-age standardized prevalence of hypertension was 22.3% (95% CI 20.6, 24.1) based on the JNC7 guideline and 36.5% (31.1, 41.8) based on the ACC/AHA guideline. A total of 24,312 participants [14.1% (10.1, 18.1)] were newly diagnosed based on the ACC/AHA guideline. Compared to adults diagnosed with hypertension based on the JNC7 guideline, the newly diagnosed participants were mainly young literate males who had low levels of risk factors and were free from conventional comorbidities of hypertension. About 30.7% (25.9, 35.4) of them (4.3% of the entire population) were eligible for pharmacologic intervention based on the ACC/AHA guideline. Implementation of the new guideline may impose additional burden on health systems. However, early detection and management of elevated blood pressure may reduce the ultimate burden of hypertension in Iran.

Single-pill sofosbuvir and daclatasvir for treating hepatis C in patients co-infected with human immunodeficiency virus.

BACKGROUND: The current recommendation for treating hepatitis C virus (HCV) in HIV patients includes the combination of sofosbuvir (SOF) and daclatasvir (DCV). DCV should be used at different doses to compensate for interactions with antiretroviral therapy (ART). Up to three pills a day might be required which will significantly add to the pill burden of these patients. In this study, we have used a single-tablet approach to treating HCV-HIV coinfection. METHODS: Patients coinfected with HIV and HCV were prospectively enrolled from 10 centers throughout the country. Patients received a single once-daily fixed dose combination (FDC) pill containing 400 mg SOF and 30, 60 or 90 mg DCV depending on the type of ART they were receiving for 12 or 24 weeks. (ClinicalTrials.gov ID: NCT03369327). RESULTS: Two hundred thirty-three patients were enrolled from 10 centers. Twenty-three patients were lost to follow-up and two patients died from causes unrelated to treatment. Two hundred eight patients completed the treatment course of which 201 achieved SVR (96.6%). CONCLUSION: Single-tablet combination of DCV and SOF is an effective and safe treatment for patients coinfected with HIV and HCV. The combination works well in patients on ART in which dose adjustment is required. Patients with cirrhosis, previous treatment failure and various genotypes respond identically. The expenses of genotyping can be saved.

Tacrolimus and mycophenolate mofetil as second-line treatment in autoimmune hepatitis: Is the evidence of sufficient quality to develop recommendations?

BACKGROUND: The standard management of autoimmune hepatitis (AIH) is based on corticosteroids, alone or in combination with azathioprine. Second-line treatments are needed for patients who have refractory disease. However, high-quality data on the alternative management of AIH are scarce. AIM: To evaluate the efficacy and safety of tacrolimus and mycophenolate mofetil (MMF) and the quality of evidence by using the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE). METHODS: A systematic review and meta-analysis of the available data were performed. We calculated pooled event rates for three outcome measures: Biochemical remission, adverse events, and mortality, with their corresponding 95% confidence intervals (CI). RESULTS: The pooled biochemical remission rate was 68.9% (95%CI: 60.4-76.2) for tacrolimus, and 59.6% (95%CI: 54.8-64.2) for MMF, and rates of adverse events were 25.5% (95%CI: 12.4-45.3) for tacrolimus and 24.1% (95%CI: 15.4-35.7) for MMF. The pooled mortality rate was estimated at 11.5% (95%CI: 7.1-18.1) for tacrolimus and 9.01% (95%CI: 6.2-12.8) for MMF. Pooled biochemical remission rates for tacrolimus and MMF in patients with intolerance to standard therapy were 56.6% (CI: 43.4-56.6) vs 73.5% (CI: 58.1-84.7), and among non-responders were 59.1% (CI: 48.7-68.8) vs 40.8% (CI: 32.3-50.0), respectively. Moreover, the overall quality assessments using GRADE proved to be very low for all our outcomes in both treatment groups. CONCLUSION: Tacrolimus and MMF are in practice considered effective for patients with AIH who are non-responders or intolerant to first-line treatment, but we found no high-quality evidence to support this statement.

The combination of sofosbuvir and daclatasvir is effective and safe in treating patients with hepatitis C and severe renal impairment.

BACKGROUND AND AIM: Many of the treatment regimens available for hepatitis C include sofosbuvir. Unfortunately, sofosbuvir has not been recommended for use in patients with severe renal impairment leaving these group of patients with very few options. Nevertheless, there are many reports in which these patients have been treated with sofosbuvir-containing regiments without important adverse events. This study aims at determining the safety and effectiveness of a sofosbuvir-based treatment in patients with severe renal impairment, including those on hemodialysis. METHOD: We enrolled subjects with hepatitis C and estimated glomerular filtration rate under ml/min/1.73m2 from 13 centers in Iran. Patients were treated for 12 weeks with a single daily pill containing 400-mg sofosbuvir and 60-mg daclatasvir. Patients with cirrhosis were treated for 24 weeks. Response to treatment was evaluated 12 weeks after end of treatment (sustained viral response [SVR]). ClinicalTrials.gov identifier: NCT03063879. RESULTS: A total of 103 patients were enrolled from 13 centers. Seventy-five patients were on hemodialysis. Thirty-nine had cirrhosis and eight were decompensated. Fifty-three were Genotype 1, and 27 Genotype 3. Twenty-seven patients had history of previous failed interferon-based treatment. Three patients died in which cause of death was not related to treatment. Six patients were lost to follow-up. The remaining 94 patients all achieved SVR. No adverse events leading to discontinuation of medicine was observed. CONCLUSIONS: The combination of sofosbuvir and daclatasvir is an effective and safe treatment for patients infected with all genotypes of hepatitis C who have severe renal impairment, including patients on hemodialysis.

Association between food insecurity and metabolic syndrome in North West of Iran: Azar Cohort study.

Introduction: Nowadays, prevalence of metabolic syndrome (MetS) is increasing in the world. There are inconsistence findings about the relationship between food insecurity and MetS. Therefore, the aim of this cross-sectional study was to determine the association between food insecurity and MetS in North West of Iran. Methods: The anthropometric measurements, food insecurity, dietary intake, blood pressure, fasting blood glucose (FBS), serum triglyceride and HDL levels of 151 subjects who had participated in Azar cohort study were evaluated. Food security was assessed by Household Food Security Scale (HFIAS) (six-item short questionnaire) and dietary intake (using 24- hour recall questionnaire) of participants. MetS was defined according to National Cholesterol Education Program's Adult Treatment Panel III report (ATPIII ) criteria. Results: On the basis of HFIAS and energy, 7.3% and 11.9% of participants were food insecure and hunger, respectively. We observed no significant differences in mean body weight, BMI, waist circumference and FBS between food insecure and secure groups. Moreover, obesity (41.7% vs 30.2%) and MetS (45.5% vs 30%) were more prevalent in the food insecure group but the differences were not significant. Conclusion: The most percent of participants in food insecure were obese and had MetS. However, we could not find significant differences between food insecure and food secure groups. Therefore, for achieving more clear results, further studies with large sample size are needed.

The Effect of Oral Administration of PUFAs on the Matrix Metalloproteinase Expression in Gastric Adenocarcinoma Patients Undergoing Chemotherapy.

OBJECTIVE: Gastric cancer is the third-leading cause of cancer-related mortality and the fifth most common cancer globally. Polyunsaturated fatty acids (PUFAs) are considered as functional ingredients that improve the efficacy of chemotherapeutic drugs. The aim of this study is to investigate the effect of PUFAs administration on matrix metalloproteinases (MMPs). METHODS: This study was designed as a randomized, double-blind trial. Thirty-four newly diagnosed patients with gastric cancer were randomly divided into two groups: control group (n = 17) and case group (n =17). Both groups received the same dose (75 mg/m2) of cisplatin. Control group received cisplatin plus placebo and the case group received cisplatin plus PUFAs [3600 mg/day, for three courses (each course included 3 weeks)]. The mRNA and protein expression of MMPs determined by real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC), respectively. RESULTS: The relative gene expression of MMP-1 and MMP-9 was significantly lower in case group than control. The protein expression of MMP-1 and MMP-9 was significantly lower in case group than control. CONCLUSION: According to the results of this study, PUFAs reduced the expression of MMPs in gastric cancer cells. It seems that PUFAs may have an inhibitory effect on invasion and metastasis of gastric cancer cells.

Effects of Pharmacologic Dose of Resveratrol Supplementation on Oxidative/Antioxidative Status Biomarkers in Nonalcoholic Fatty Liver Disease Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.

Purpose: Despite a proposed role for oxidative stress in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), antioxidant approaches have not been sufficiently investigated in human NAFLD management. Resveratrol has been reported to possess a wide range of biological functions, including antioxidant activities. This study aimed to evaluate the effects of resveratrol supplementation on oxidative/anti-oxidative status in patients with NAFLD. Methods: This randomized, double-blind, placebo-controlled clinical trial was conducted on 60 patients with NAFLD (males and females) aged 20 to 60 years, and body mass index (BMI) of 25-35 kg/m2. Subjects were randomly assigned to receive a daily dose of 600 mg resveratrol (2×300 mg pure trans-resveratrol capsules; n=30) or placebo capsules (n=30) for 12 wk. Fasting blood samples, anthropometric measurements, and dietary intakes were collected for all patients at baseline and at the end of the trial. Oxidative stress was evaluated by measurement of serum malondialdehyde (MDA), oxidized low-density lipoprotein (ox-LDL), total antioxidant capacity (TAC), and erythrocyte superoxide dismutase (SOD) as well as glutathione peroxidase (GSH-Px) activities. Changes in the outcomes were analyzed using analysis of covariance (ANCOVA). Results: Resveratrol supplementation did not significantly affect neither serum MDA, ox-LDL, and TAC levels, nor erythrocyte SOD and GSH-Px activities, compared to placebo group (All P>0.05). Moreover, changes in serum levels of liver enzymes (ALT, AST, GGT, and ALP) were not significant in neither of the study groups (All P>0.05). Conclusion: Resveratrol supplementation did not modify oxidative/anti-oxidative status in patients with NAFLD.

Comparison of Calorie-Restricted Diet and Resveratrol Supplementation on Anthropometric Indices, Metabolic Parameters, and Serum Sirtuin-1 Levels in Patients With Nonalcoholic Fatty Liver Disease: A Randomized Controlled Clinical Trial.

OBJECTIVE: There is a promising perspective regarding the potential effect of resveratrol in preventing and treating metabolic disturbances similar to that of calorie restriction. The aim of this study was to evaluate the effects of calorie-restricted (CR) diet on metabolic parameters and then to investigate whether resveratrol supplementation has beneficial effects similar to CR diet in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: This randomized controlled clinical trial was conducted in 90 patients with NAFLD (males and females) aged 20 to 60 years with body mass index (BMI) ranging from 25 to 35 kg/m2. Participants were assigned to one of three intervention groups as follows: The CR diet group (n = 30) received a prescribed low-calorie diet, the resveratrol group (n = 30) received 600 mg pure trans-resveratrol (2 × 300 mg) daily, and the placebo group (n = 30) received placebo capsules (2 × 300 mg) daily for 12 weeks. Fasting blood samples, anthropometric measurements, and dietary intake and physical activity data were collected for all participants at baseline and at the end of the trial. RESULTS: CR diet significantly reduced weight (by 4.5%); BMI; waist circumference; waist-to-hip ratio; and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lipid profiles in participants compared to resveratrol and placebo (all p < 0.05). Significant reductions in weight (by 1.1%) and BMI were found in the resveratrol group compared to the placebo group (p < 0.05). ALT, AST, and lipid profiles did not change significantly in the resveratrol group (all p > 0.05). No significant changes were seen in hepatic steatosis grade, serum glycemic parameters, and high-density lipoprotein cholesterol and sirtuin-1 levels in any group (all p > 0.05). CONCLUSIONS: CR diet with moderate weight loss has favorable effects on NAFLD, and resveratrol supplementation induced weight loss but failed to mimic other aspects of CR diet. Future studies are warranted to evaluate the long-term and dose-dependent effects of resveratrol on metabolic diseases.

Common chemotherapeutic agents modulate fatty acid distribution in human hepatocellular carcinoma and colorectal cancer cells.

Introduction: Cancer cells are critically correlated with lipid molecules, particularly fatty acids, as structural blocks for membrane building, energy sources, and related signaling molecules. Therefore, cancer progression is in direct correlation with fatty acid metabolism. The aim of this study was to investigate the potential effects of common chemotherapeutic agents on the lipid metabolism of hepatocellular carcinoma (HCC) and colorectal cancer (CRC) cells, with a focus on alterations in cellular fatty acid contents. Methods: Human HepG2 and SW480 cell lines as HCC and CRC cells were respectively cultured in RPMI-1640 medium supplemented with non-toxic doses of 5-fluorouracil and doxorubicin for 72 hours. Oil Red O dye was used to estimate intracellular lipid vacuole intensity. Fatty acid analysis of isolated membrane phospholipids and cytoplasmic triglycerides (TG) was performed by gas-liquid chromatography (GLC) technique. Results: Oil red O staining represented significantly higher lipid accumulation and density in cancer cells after exposure to the chemotherapeutic agents as compared to non-treated control cells. Doxorubicin and 5-fluorouracil treatment promoted the channeling of saturated fatty acids (SFAs) from phospholipids to triglyceride pool in both HepG2 (+5.91% and +8.50%, P < 0.05, respectively) and SW480 (+37.41% and +5.73%, P < 0.05, respectively) cell lines. However, total polyunsaturated fatty acid content was inversely shifted from TG to phospholipid fraction after doxorubicin and 5-fluorouracil incubation of HepG2 (+58.89% and +29.13%, P < 0.05, respectively) and SW480 (+19.20% and +14.65%, P < 0.05, respectively) cells. Conclusion: Our data showed that common chemotherapeutic agents of HCC and CRC can induce significant changes in cellular lipid accumulation and distribution of fatty acids through producing highly saturated and unsaturated lipid droplets and membrane lipids, respectively. These metabolic side effects may be associated with gastrointestinal cancers treatment failure.

Effect of PUFAs Oral Administration on the Amount of Apoptotic Caspases Enzymes in Gastric Cancer Patients Undergoing Chemotherapy.

OBJECTIVE: Gastric cancer is the fourth most common cancer and the second cause of death in the world. According to the studies, the gastric cancer is relatively sensitive to chemotherapy. The aim of this study was to investigate the association of oral administer PUFAs with Caspase enzymes in patients with gastric cancer under chemotherapy. METHODS: This study was a Clinical Trial in which the target group consisted of the patients recognized with gastric cancer for the first time and cured under chemotherapy. Thirty-four patients were selected and categorized randomly into two groups. The case group included the patients taking PUFAs along with chemotherapeutic agent. In these patients, chemotherapy started with Cis-Platin plus PUFAs supplement in the scale of 3600 mg daily and in three courses. In control group, the individuals were under the same chemotherapy protocol without PUFAs. Biopsy samples from tumor were taken from the patients before and after chemotherapy. Levels of mRNA and protein expression of caspase 3, 8, 9 were measured in biopsy samples by Real-Time PCR and Frozen Section methods. The levels of apoptosis were determined using DNA-damage colorimetric assay. RESULTS: In the case group, caspase 3 showed a significant increase in both gene and protein expression levels after administration of PUFAs supplement in comparison with those of the control group (p=0.006 for gene, p=0.001 for protein). PUFAs induced caspase-9 gene expression level in these patients (p<0.0001). Caspase-9 protein level also revealed a marked elevation when PUFAs were administered along with chemotherapeutic agent (p<0.0001). DNA damage in gastric tissue from the patients under PUFAs treatment plus Cis-Platin was significantly higher than that of control group (p=0.003). PUFAs showed no significant changes in caspase-8 both at the gene and protein levels in the patients. CONCLUSION: According to the results of present study, it appears that oral administration of PUFAs can elevate the efficacy of chemotherapy agent in individuals' mitochondria-dependent apoptosis. As PUFAs enhances caspase-3 and 9 genes expression levels, which is an important induce the mitochondrial dependent apoptosis process. The study was registered in Iran clinical trials registry center under No. IRCT2014031016922N1.

Non-invasive serum fibrosis markers: A study in chronic hepatitis.

INTRODUCTION: Chronic hepatitis is specified as inflammatory disease of the liver lasting for more than six months. Role of noninvasive fibrosis markers as prognostication factors of the presence or absence of significant fibrosis on liver biopsy of patients with chronic hepatitis is the aim of this study. METHODS: Two hundred twenty-one patients with chronic hepatitis involved in the study between 2011 and 2013. Routine biochemical indices and serum fibrosis markers such as aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), AST to platelet ratio index (APRI) and Fibrosis 4 score (FIB-4) were evaluated, and the histological grade and stage of the liver biopsy specimens were scored according to the Ishak scoring system. Diagnostic accuracies of these markers for prediction of significant fibrosis were assessed by Receiver Operating Characteristic (ROC) curve analysis. RESULTS: Contemporaneous laboratory indices for imputing AAR, APRI, and FIB-4 were identified with liver biopsies. From all, 135 males (61.1%) and 86 females (38.9%), with mean age of 39.6±14.4 were studied. Significant correlation between stages of fibrosis and FIB-4, APRI and AAR were detected, with a correlation coefficient higher than that of other markers in the patients with Hepatitis B (r = 0.46), C (r = 0.58) and autoimmune hepatitis (r = 0.28). FIB-4 (AUROC = 0.84) and APRI (AUROC = 0.78) were superior to AAR at distinguishing severe fibrosis from mild-to-moderate fibrosis and gave the highest diagnostic accuracy. CONCLUSION: Application of these markers was good at distinguishing significant fibrosis and decreased the need for staging liver biopsy specimens among patients with chronic hepatitis.

Liver mass due to penetration of a silent duodenal ulcer.

Liver penetration is a rare but serious complication of peptic ulcer disease. We report a 60-year-old man, without any serious risk factor for peptic ulcer, presented with mild abdominal discomfort, food-related vomiting and weight loss, and a mass in the left hepatic lobe, which was the result of a silent duodenal ulcer penetration. The diagnosis was based on histological examination of the endoscopic biopsies.

Abdominal pain due to lead-contaminated opium: a new source of inorganic lead poisoning in Iran.

Although the incidence of occupational and adult lead poisoning has declined, the problem still exists. We encountered three patients with lead poisoning in Iran, all of whom associated with presented with diffuse abdominal pain, which was at times colicky in nature, anemia, constipation, nausea, vomiting, and slightly abnormal liver biochemistries. A history of opium ingestion was present in each of these patients. None of the patients reported known occupational exposure to toxins. Diagnoses of lead poisoning were confirmed through the detection of elevated blood lead levels. The cause of lead poisoning was attributed to the ingestion of contaminated opium. Opium adulterated with lead had not been previously recognized as a source of lead poisoning in Iran. It is, therefore, pointed out that lead poisoning should be considered as a differential diagnosis for acute abdominal colic of unclear cause in patients with opium addiction.