Preparation, Characterization, and Anticancer Activity Assessment of Chitosan/TPP Nanoparticles Loaded with Echis carinatus Venom.

AIMS AND BACKGROUND: Echis carinatus venom is a toxic substance naturally produced by special glands in this snake species. Alongside various toxic properties, this venom has been used for its therapeutic effects, which are applicable in treating various cancers (liver, breast, etc.). OBJECTIVE: Nanotechnology-based drug delivery systems are suitable for protecting Echis carinatus venom against destruction and unwanted absorption. They can manage its controlled transfer and absorption, significantly reducing side effects. METHODS: In the present study, chitosan nanoparticles were prepared using the ionotropic gelation method with emulsion cross-linking. The venom's encapsulation efficiency, loading capacity, and release rate were calculated at certain time points. Moreover, the nanoparticles' optimal formulation and cytotoxic effects were determined using the MTT assay. RESULTS: The optimized nanoparticle formulation increases cell death induction in various cancerous cell lines. Moreover, chitosan nanoparticles loaded with Echis carinatus venom had a significant rate of cytotoxicity against cancer cells. CONCLUSION: It is proposed that this formulation may act as a suitable candidate for more extensive assessments of cancer treatment using nanotechnology-based drug delivery systems.

Therapeutic effect of 5-ASA and hesperidin-loaded chitosan/Eudragit® S100 nanoparticles as a pH-sensitive carrier for local targeted drug delivery in a rat model of ulcerative colitis.

Ulcerative colitis (UC) is an idiopathic disease characterized by colonic mucosal tissue destruction secondary to an excessive immune response. We synthesized pH-sensitive cross-linked chitosan/Eudragit® S100 nanoparticles (EU S100/CS NPs) as carriers for 5-aminosalicylic acid (5-ASA) and hesperidin (HSP), then conducted in-vitro and in-vivo studies and evaluated the therapeutic effects. In-vitro analysis revealed that the 5-ASA-loaded EU S100/CS NPs and the HSP-loaded EU S100/CS NPs had smooth and curved surfaces and ranged in size between 250 and 300 nm, with a zeta potential of 32 to 34 mV. FTIR analysis demonstrated that the drugs were loaded on the nanoparticles without significant alterations. The loading capacity and encapsulation efficiency of loading 5-ASA onto EU S100/CS NPs were 25.13 % and 60.81 %, respectively. Regarding HSP, these values were 38.34 % and 77.84 %, respectively. Drug release did not occur in simulated gastric fluid (SGF), while a slow-release pattern was recorded for both drugs in simulated intestinal fluid (SIF). In-vivo macroscopic and histopathological examinations revealed that both NPs containing drugs significantly relieved the symptoms of acetic acid (AA)-induced UC in Wistar rats. We conclude that the synthesized pH-sensitive 5-ASA/EU S100/CS NPs and HSP/EU S100/CS NPs offer promise in treating UC.

Synthesis, characterization and hepatoprotective effect of silymarin phytosome nanoparticles on ethanol-induced hepatotoxicity in rats.

Introduction: Silymarin proved to be a beneficial herbal medicine against many hepatic disorders such as alcoholic liver disease (ALD). However, its application is restricted due to its low bioavailability and consequently decreased efficacy. We herein used a nano-based approach known as "phytosome", to improve silymarin bioavailability and increase its efficacy. Methods: Phytosome nanoparticles (NPs) were synthesized using thin film hydration method. NPs size, electrical charge, morphology, stability, molecular interaction, entrapment efficiency (EE %) and loading capacity (LC %) were determined. Moreover, in vitro toxicity of NPs was investigated on mesenchymal stem cells (MSCs) viability using MTT assay. In vivo experiments were performed using 24 adult rats that were divided into four groups including control, ethanol (EtOH) treatment, silymarin/EtOH treatment and silymarin phytosome/EtOH, with 6 mice in each group. Experimental groups were given 40% EtOH, silymarin (50 mg/kg) and silymarin phytosome (200 mg/kg) through the gastric gavage once a day for 3 weeks. Biochemical parameters, containing ALP, ALT, AST, GGT, GPx and MDA were measured before and after experiment to investigate the protective effect of silymarin and its phytosomal form. And histopathological examination was done to evaluate pathological changes. Results: Silymarin phytosome NPs with the mean size of 100 nm were produced and were well tolerated in cell culture. These NPs showed a considerable protective effect against ALD through inverting the biochemical parameters (ALP, ALT, AST, GGT, GPx) and histopathological alterations. Conclusion: Silymarin phytosomal NPs can be used as an efficient treatment for ALD.

pH-sensitive HPMCP-chitosan nanoparticles containing 5-aminosalicylic acid and berberine for oral colon delivery in a rat model of ulcerative colitis.

Ulcerative colitis (UC) with continuous and extensive inflammation is limited to the colon mucosa and can lead to abdominal pain, diarrhea, and rectal bleeding. Conventional therapies are associated with several limitations, such as systemic side effects, drug degradation, inactivation, and limited drug uptake, leading to poor bioavailability. These restrictions necessitate drug delivery to the colon so that the drug passes through the stomach unchanged and has selective access to the colon. The present study aimed to formulate 5-aminosalicylic acid (5-ASA) and berberine (BBR) in chitosan nanoparticles cross-linked by HPMCP (hydroxypropyl methylcellulose phthalate) as a colon drug delivery system for UC. Spherical nanoparticles were prepared. They showed appropriate drug release in the simulated intestinal fluid (SIF), while the release did not occur in the simulated gastric fluid (SGF). They improved disease activity parameters (DAI) and ulcer index, increased the length of the colon, and decreased the wet weight of the colon. Furthermore, histopathological colon studies showed an improved therapeutic effect of 5-ASA/HPMCP/CSNPs and BBR/HPMCP/CSNPs. In conclusion, although 5-ASA/HPMCP/CSNPs showed the best effect in the treatment of UC, BBR/HPMCP/CSNPs, and 5-ASA/BBR/HPMCP/CSNPs were also effective in vivo study, and this study anticipated they could be helpful in future clinical applications for the management of UC.

Reactogenicity within the first week after Sinopharm, Sputnik V, AZD1222, and COVIran Barekat vaccines: findings from the Iranian active vaccine surveillance system.

BACKGROUND: This study aimed to evaluate the reactogenicity effects of COVID-19 vaccines, used in Iran. METHODS: At least 1000 people were followed up with phone calls or self-report in a mobile application within 7 days after vaccination. Local and systemic reactogenicities were reported overall and by subgroups. RESULTS: The presence of one or more local and systemic adverse effects after the first dose of vaccines was 58.9% [(95% Confidence Intervals): 57.5-60.3)] and 60.5% (59.1-61.9), respectively. These rates were reduced to 53.8% (51.2-55.0) and 50.8% (48.8-52.7) for the second dose. The most common local adverse effect reported for all vaccines was pain in the injection site. During the first week after the first dose of vaccines, the frequency of the pain for Sinopharm, AZD1222, Sputnik V, and Barekat was 35.5%, 86.0%, 77.6%, and 30.9%, respectively. The same rates after the second dose were 27.3%, 66.5%, 63.9%, and 49.0%. The most common systemic adverse effect was fatigue. In the first dose, it was 30.3% for Sinopharm, 67.4% for AZD1222, 47.6% for Sputnik V, and 17.1% for Barekat. These rates were reduced to 24.6%, 37.1%, 36.5%, and 19.5%, in the second dose of vaccines. AZD1222 had the highest local and systemic adverse effects rates. The odds ratio of local adverse effects of the AZD1222 vaccine compared to the Sinopharm vaccine were 8.73 (95% CI 6.93-10.99) in the first dose and 4.14 (95% CI 3.32-5.17) in the second dose. Barekat and Sinopharm had the lowest frequency of local and systemic adverse effects. Compared to Sinopharm, systemic adverse effects were lower after the first dose of Barekat (OR = 0.56; 95% CI 0.46-0.67). Reactogenicity events were higher in women and younger people. Prior COVID-19 infection increased the odds of adverse effects only after the first dose of vaccines. CONCLUSIONS: Pain and fatigue were the most common reactogenicities of COVID-19 vaccination. Reactogenicities were less common after the second dose of the vaccines. The adverse effects of AZD1222 were greater than those of other vaccines.

COVID-19 cases, hospitalizations and deaths after vaccination: a cohort event monitoring study, Islamic Republic of Iran.

Objective: To investigate the incidence of coronavirus disease 2019 (COVID-19) cases, hospitalizations and deaths in Iranians vaccinated with either AZD1222 Vaxzevria, CovIran® vaccine, SARS-CoV-2 Vaccine (Vero Cell), Inactivated (lnCoV) or Sputnik V. Methods: We enrolled individuals 18 years or older receiving their first COVID-19 vaccine dose between April 2021 and January 2022 in seven Iranian cities. Participants completed weekly follow-up surveys for 17 weeks (25 weeks for AZD1222) to report their COVID-19 status and hospitalization. We used Cox regression models to assess risk factors for contracting COVID-19, hospitalization and death. Findings: Of 89 783 participants enrolled, incidence rates per 1 000 000 person-days were: 528.2 (95% confidence interval, CI: 514.0-542.7) for contracting COVID-19; 55.8 (95% CI: 51.4-60.5) for hospitalization; and 4.1 (95% CI: 3.0-5.5) for death. Compared with SARS-CoV-2 Vaccine (Vero Cell), hazard ratios (HR) for contracting COVID-19 were: 0.70 (95% CI: 0.61-0.80) with AZD1222; 0.73 (95% CI: 0.62-0.86) with Sputnik V; and 0.73 (95% CI: 0.63-0.86) with CovIran®. For hospitalization and death, all vaccines provided similar protection 14 days after the second dose. History of COVID-19 protected against contracting COVID-19 again (HR: 0.76; 95% CI: 0.69-0.84). Diabetes and respiratory, cardiac and renal disease were associated with higher risks of contracting COVID-19 after vaccination. Conclusion: The rates of contracting COVID-19 after vaccination were relatively high. SARS-CoV-2 Vaccine (Vero Cell) provided lower protection against COVID-19 than other vaccines. People with comorbidities had higher risks of contracting COVID-19 and hospitalization and should be prioritized for preventive interventions.

The effect of sesame oil consumption compared to sunflower oil on lipid profile, blood pressure, and anthropometric indices in women with non-alcoholic fatty liver disease: a randomized double-blind controlled trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in the world. There is strong evidence that dyslipidemia and other cardio-metabolic disorders are highly prevalent in patients with NAFLD. This trial aimed at examining the effect of sesame oil (SO) in the context of a weight loss program on lipid profile, blood pressure, and anthropometric indices in women with NAFLD. METHODS: This randomized, double-blind, controlled trial was carried out on 60 women with NAFLD. Subjects were randomly assigned to the SO group (n = 30) and sunflower oil (SFO) group (n = 30), each person consuming 30 g of oil per day for 12 weeks. All the participants received a hypocaloric diet (- 500 kcal/day) during the study. Lipid profile, blood pressure, and anthropometric indices were assessed at pre- and post-intervention phases. RESULTS: In total, 53 participants completed the study. Following 12 weeks of intervention, anthropometric indices (p < 0.001) and systolic blood pressure (SBP) (p < 0.05) were significantly decreased in both groups and diastolic blood pressure (DBP) was significantly decreased in So group (p = 0.03). There was no significant change in lipid profile in both groups (p > 0.05). After adjusting for confounders, DBP (p = 0.031) and total cholesterol (TC) divided by high-density lipoprotein cholesterol (HDL-C) (p = 0.039) in the SO group were significantly reduced compared to the SFO group (p < 0.05). CONCLUSIONS: The present clinical trial revealed that SO and SFO may not differently affect anthropometric indices, SBP, and lipid profile except for TC/HDL-C. In addition, SO may be effective in improvement of DBP and TC/HDL-C compared to the SFO group. TRIAL REGISTRATION: Ethical approval of this trial was obtained at Isfahan University of Medical Sciences with the reference number of IR.MUI. RESEARCH: REC.1399.548 ( https://ethics. RESEARCH: ac.ir/ProposalCertificateEn.php?id=158942&Print=true&NoPrintHeader=true&NoPrintFooter=true&NoPrintPageBorder=true&LetterPrint=true ), and it was registered before the start of the patient recruitment on December 12th, 2020 in the Iranian Registry of Clinical Trials (IRCT) with the registration number of IRCT20140208016529N6 .

The effects of sesame oil on metabolic biomarkers: a systematic review and meta-analysis of clinical trials.

Background: Clinical evidences showing the effects of sesame oil on metabolic biomarkers led to inconsistent results. Propose: This meta-analysis was designed to examine the effects of sesame oil on metabolic biomarkers in adults, including the maximum number of clinical trials. Methods: Google Scholar, PubMed, Web of Science, and Scopus were systematically searched to date up to July 2021 to identify eligible clinical trial studies. We obtained the pooled estimates of weighted mean differences (WMDs) with their 95% confidence intervals (CIs) using random-effects meta-analysis. Result: Meta-analysis showed that sesame oil consumption significantly lowered the levels of fasting blood glucose (FBG) (WMD: -3.268 mg/dl; 95% CI: -4.677, -1.86; P < 0.001), and malondialdehyde (MDA) (WMD: -4.847 nmol/dL; 95% CI: -7.051, -2.698; P < 0.001) between the intervention and control groups. Also, this study showed sesame oil consumption significantly decreased HbA1C (WMD: -2.057%; 95% CI: -3.467, -0.646; P = 0.004), systolic blood pressure (SBP) (WMD: -2.679 mmHg; 95% CI: -5.257, -0.101; P < 0.001), diastolic blood pressure (DBP) (WMD: -1.981 mmHg; 95% CI: -3.916, -0.046; P = 0.045), body weight (WMD: -0.346 kg; 95% CI: -0.641, -0.051; P = 0.021), and body mass index (BMI) (WMD: -0.385 kg/m2; 95% CI:-0.721, -0.049; P = 0.025) after intervention. No significant effect was seen in serum insulin levels (p > .05). Conclusions: The current study provided some evidence regarding the beneficial effects of sesame oil on metabolic biomarkers. Further studies are still required to confirm our results. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-00997-2.

Sesame Oil Ameliorates Alanine Aminotransferase, Aspartate Aminotransferase, and Fatty Liver Grade in Women with Nonalcoholic Fatty Liver Disease Undergoing Low-Calorie Diet: A Randomized Double-Blind Controlled Trial.

Background: The type and amount of dietary fats play an important role in fat accumulation in the liver. Sesame oil (SO) is a good source of monounsaturated acids (MUFAs) and polyunsaturated fatty acids (PUFAs). Objective: This trial aimed at examining the effect of SO consumption on the levels of liver enzymes and the severity of fatty liver in women with nonalcoholic fatty liver disease (NAFLD) undergoing a weight loss diet. Methods: This randomized, double-blind, controlled trial was carried out on 60 women with NAFLD. Subjects were randomly assigned to the SO group (n = 30) and sunflower oil (SFO) group (n = 30), each person consuming 30 grams of oil per day for 12 weeks. All the participants received a hypocaloric diet (-500 kcal/day) during the study. Fatty liver grade and liver enzymes were assessed at pre- and postintervention phases. Results: 53 patients completed the study. Significant reductions in body weight, body mass index (BMI), waist circumference (WC), and fatty liver grade were observed in both groups (P < 0.05). Following SO, significant decreases in serum aspartate and alanine aminotransferases (AST and ALT) were observed. After adjusting for confounders, ALT, AST, and fatty liver grade of the SO group were significantly reduced compared to the SFO group (P < 0.05). However, the changes in serum alkaline phosphatase (ALP) were not significant (P > 0.05). Conclusions: The desired effects of weight loss were reinforced by the consumption of SO through improving fatty liver severity and serum ALT and AST levels in NAFLD patients. Moreover, low-calorie diets may lead to favorable outcomes for NAFLD patients through mitigation of obesity and fatty liver grade.

Urbanization Levels and Its Association with Prevalence of Risk Factors and Colorectal Cancer Incidence.

BACKGROUND: Colorectal cancer is one of the most common cancers in the world. This study aimed to determine the relationship between risk factors and the incidence of colorectal cancer in Urbanization levels in Iran. METHODS: This was a population-based study. Urbanization levels were determined using the census data of the Statistical Center in 2012. Data on risk factors for colorectal cancer were obtained from the information provided by the Iranian Non-Communicable Disease Control Center and the incidence of colorectal cancer from the data from the National Cancer Registry System. Negative binomial regression analysis was used to determine the relationship between colorectal cancer risk factors and urbanization levels with colorectal cancer incidence. For statistical analysis, SPSS and Stata software were used. A significant level of P≤0.05 was considered. RESULTS: The relationship between urbanization levels and risk factors with the incidence of colorectal cancer, nutrition Status, tobacco use, and body mass index were not significant. There was a significant relationship between physical activity and incidence at different levels and between levels of urbanization and incidence rate, indicating a lower incidence rate of colorectal cancer at lower levels of urbanization. CONCLUSION: Colorectal cancer incidence is higher at higher levels of urbanization than lower levels. The difference between regions in terms of urbanization can have in flounce on access to facilities, health service, and counseling opportunities to modify the risk factors and access to proper screening and follow-up care.

Kaolin-loaded chitosan/polyvinyl alcohol electrospun scaffold as a wound dressing material: in vitro and in vivo studies.

OBJECTIVE: To evaluate the application of a fabricated dressing containing kaolin for skin regeneration in a rat model of excisional wounds. METHOD: In the present study, kaolin was loaded into electrospun polyvinyl alcohol (PVA)/chitosan polymer blend to develop a composite nanofibrous dressing. To make the yarns, kaolin with weight ratio of 5% was added to PVA/chitosan polymer blend and subsequently formed into nanofibres using the electrospinning method. Scaffolds were evaluated for to their microstructure, mechanical properties, surface wettability, water vapour transmission rate, water-uptake capacity, blood uptake capacity, blood compatibility, microbial penetration test, the number of colonies, and cellular response with the L929 cell line. Rats with full-thickness excisional wounds were treated with kaolin-containing and kaolin-free dressings. RESULTS: The study showed that rats treated with the kaolin-incorporated mats demonstrated a significant closure to nearly 97.62±4.81% after 14 days compared with PVA/chitosan and the sterile gauze, which showed 86.15±8.11% and 78.50±4.22% of wound closure, respectively. The histopathological studies showed that in the PVA/chitosan/kaolin group, dense and regular collagen fibres were formed, while wounds treated with sterile gauze or PVA/chitosan scaffolds had random and loose collagen fibres. CONCLUSION: Our results show the potential applicability of PVA/chitosan/kaolin scaffolds as a wound care material.

Evaluation of empowerment model on indicators of metabolic control in patients with type 2 diabetes, a randomized clinical trial study.

AIMS: Diabetes education is a major subject in achieving optimal glycemic control. Effective empowerment approach can be beneficial for improving patients' health. The aim of this study was to evaluate the effect of empowerment model on indicators of metabolic control in patients with type 2 diabetes. METHODS: a randomized controlled trial of 103 patients with type 2 diabetes were randomly assigned to either the intervention (empowerment approach training) or the control group (conventional training) 2014. Empowerment approach training were performed for the experimental group for eight weeks. Data collection tool included demographic information form and indicators of metabolic control checklist. Analysis was performed by one-way analysis of variance, chi-square test, paired t-test, independent t-test and multiple linear regression. RESULTS: Before the intervention, two groups were homogeneous in terms of demographic variables, glycosylated hemoglobin (HbA1C), and other indicators of metabolic control. After the intervention, average HbA1C and other metabolic indicators except for LDL showed significant differences in the experimental group compared to the control group. CONCLUSION: study results indicated the positive effects of applying the empowerment model on the metabolic control indicators. Therefore, applying this model is recommended to nurses and the relevant authorities in order to improve clinical outcomes in diabetic patients.

Smoking and Its Related Factors Among Iranian High School Students.

BACKGROUND: In different studies, the prevalence of tobacco consumption has been growing in high schools boys. OBJECTIVES: This study was conducted to determine the prevalence of smoking and its related factors among Iranian high school students in 2011. MATERIALS AND METHODS: In this cross-sectional study, 450 male students from 15 high schools of Shahroud (northeast of Iran) were selected for evaluation of the knowledge, attitude and practices (KAP) of students regarding tobacco consumption. RESULTS: Overall, 51% (95% CI: 46.5 - 55.7) of the students had positive history of smoking for at least one time and 7.1% (95% CI: 5 - 10) of them were current smokers. The most prevalent source of information about smoking was TV and radio programs (48%) and friends were the second source (22%). Based on the students' opinions, entertainment and smoker friends were the most important reasons for smoking tendency. There was significant statistical association between students smoking and positive family history of smoking (P value < 0.05). CONCLUSIONS: The prevalence of smoking experince was very high among high school students. The most prevalent source of information about smoking was Iranian broadcasting companies. Positive family history of smoking and smoker friends were the important motivating factors toward smoking.