Nanofabrication of chitosan-based dressing to treat the infected wounds: in vitro and in vivo evaluations.

Aim: Here, an innovative kind of antibacterial nanocomposite film is developed by incorporating graphene oxide and zinc oxide into chitosan matrix. Materials & methods: Our dressing was fabricated using the solution casting method. Fourier transform infrared spectra and TGA-DTG clearly confirmed the structure of film dressing. Results & conclusion: Our results showed the tensile strength and elongation at the break of the films were 20.1 ± 0.7 MPa and 36 ± 10%, respectively. Our fabricated film could absorb at least three-times the fluid of its dry weight while being biocompatible, antibacterial, non-irritant and non-allergic. In addition, it accelerated the healing process of infected wounds by regulating epithelium thickness and the number of inflammatory cells, thus it may be useful for direct application to damaged infected wounds.

In this study, an innovative kind of antibacterial nanocomposite film is developed by incorporating graphene oxide and zinc oxide into chitosan matrix. Our antibacterial wound dressing was fabricated using the solution casting method. Our fabricated film could absorb at least three-times the fluid of its dry weight while being biocompatible, antibacterial, non-irritant and non-allergic. In addition, our film accelerated the healing process of infected wounds by regulating epithelium thickness and the number of inflammatory cells. thus it may be useful for direct application to damaged infected wounds.

The Effect of Warmed Serum on Shivering and Recovery Period of Patients Under General and Spinal Anesthesia: A Randomized Clinical Trial.

PURPOSE: Postoperative hypothermia followed by shivering is a common phenomenon in patients undergoing surgery under anesthesia, and should be prevented and treated in postoperative patient care units. This study was conducted to investigate the effect of warmed serum injection on postoperative shivering and recovery period of patients operated under general and spinal anesthesia. DESIGN: In this clinical trial, patients to be operated on under general and spinal anesthesia were randomly assigned into two groups of test and control. In the test group, patients received warmed intravenous fluids and blood products. All patients were monitored to record vital signs, incidences of hypothermia and shivering, and recovery period. METHODS: The collected data were analyzed with repeated measures analysis of variance to detect significant differences between groups and significant changes within groups over time. FINDINGS: The incidence of nausea, vomiting, and shivering in the intervention and control groups was (4.7%, 42%), (2.8%, 16.8%), and (6.6%, 43%), respectively. Patients in the intervention group had higher body temperature than the control group (<0.001). Also, patients under spinal anesthesia had higher body temperature than patients under general anesthesia (<0.001). Blood pressure reduction was also significantly higher in the control group than in the intervention group. The patients who received warm intravenous serum, and especially those who had received spinal anesthesia spent less time in the recovery room (<0.001). CONCLUSIONS: The use of warmed intravenous serum increased the patients' core temperature, reduced their postoperative shivering, and shortened their recovery period. Considering the potential risks associated with hypothermia, using such methods for hypothermia prevention can be highly effective in preventing shivering and prolongation of the recovery period and other potential complications. Anesthesia specialists and technicians are therefore encouraged to use this method as a preventive measure.

Biocatalytic synthesis of oxadiazole thioethers and evaluation of their antitumor activity.

A multicomponent enzyme-catalyzed process is suggested for the synthesis of a novel series of 1,3,4-oxadiazole thioether derivatives with yields ranging from 65 to 94%. Novozym 435, the immobilized form of Candida antarctica lipase B (CALB), was found to efficiently catalyze the reaction. The products were evaluated for antitumor activities against two cancer cell lines, HT-29 (human colorectal cancer cell) and HepG2 (human liver cancer cell), by MTT assays. Among them, two compounds exhibited higher antitumor activities, for both cell lines, compared to doxorubicin. In silico molecular docking and computational ADME analysis were performed to propose a mode of action for the anti-cancer activities and to predict drug-likeness, respectively.

Chitosan nanoparticle loaded by epidermal growth factor as a potential protein carrier for wound healing: In vitro and in vivo studies.

Epidermal growth factor (EGF) can be efficiently used in wound healing process; but the main obstacle of its clinical use is its susceptibility to proteolysis and maintaining its effective concentration in the site of action. In this study, chitosan nanoparticles containing EGF is formulated using a simple method to increase its stability in physiological pH as well as protect its biological activity and effectiveness in wound healing process. Nanoparticles with different ratios of chitosan/EGF were prepared and evaluated in vitro and in vivo. Obtained results showed nanoparticles with 2:1 ratio of chitosan/EGF were able to release 80% of encapsulated protein after 12 h. Cell proliferation study demonstrated that prepared nanoparticles could protect EGF functionality in physiological pH. In vivo results showed that nanoparticles with 2:1 ratio of chitosan/EGF could significantly accelerate the wound closure-rate, re-epithelialisation and collagen deposition. In conclusion, the designed nanoparticles in optimal ratio can be considered as a potential vehicle for EGF delivery to wounds with the aim of improving healing process.

Diarylation of thiazolopyrimidines by laccase and their in vitro evaluation as antitumor agents.

A mild and efficient method was developed for the synthesis of new derivatives of thiazolo[3,2-a] pyrimidin-3(2H)-ones from available starting materials based on the oxidation of catechols to ortho-quinone by Myceliophthora thermophila laccase (Novozym 51,003) and 1,4-addition of active methylene carbon to these in situ generated intermediates in moderate to good yields (35-93%). The structure of the products was confirmed through 1H NMR, 13C NMR, HMBC, HSQC, DEPT-135, and mass spectroscopy techniques. These novel compounds were evaluated as active antitumor agents against human colorectal adenocarcinoma and liver adenocarcinoma cell lines. All compounds displayed potent inhibition activities against the HT-29 cell line with IC50 values of 9.8-35.9 µM, superior to the positive control doxorubicin, and most showed potent anticancer activities against the HepG2 cell line.

Determination of Phthalate Esters in Cosmetics and Baby Care Products by a Biosorbent Based on Lawsone Capped Chitosan and Followed by Liquid Chromatography.

This research presents a green synthetic pathway for the preparation of a new biosorbent and eco-friendly extraction process of three phthalate esters: dimethyl phthalate, di-butyl phthalate and benzyl butyl phthalate, from cosmetics and baby care products. Dispersive solid-phase extraction was used based on a new core-shell biomass/sorbent; chitosan-loaded lawsone. The proposed method provides fortunate trapping of phthalate esters in a one-step extraction. Under the optimized extraction conditions, the current work was presented low detection limits (0.03-0.15 ng. g-1), limits of quantification (0.1-0.5 ng·g-1) and reasonable linearity (0.1-10 000 ng. g-1). The applicability of the method was estimated by recovery experiments at different spiking levels (n = 5) for phthalate esters in the real samples.

The association between lunch composition and obesity in Iranian adults.

We aimed to assess the dietary composition of lunch meal using a posteriori-derived dietary patterns and to determine the association of lunch composition with obesity in a sample of Iranian adults. This cross-sectional study was conducted on 850 men and women in Tehran (aged 20-59 years). Dietary intakes were assessed using three 24-h dietary recalls, and dietary patterns were identified via principal component factor analysis. For each identified pattern, scores were calculated for each participant and then classified into tertiles. Central obesity was defined WHO criteria. General obesity was defined as a BMI of more than 30 kg/m2. Three major dietary patterns were identified at lunch meal using twelve food groups: 'Bread, grains and fat', 'Western' and 'Potato and eggs'. After adjustment for potential confounders, participants at the top tertile of the 'Bread, grains and fat' dietary pattern had greater odds for a higher waist-to-hip ratio (WHR), compared with those in the lowest tertile (OR: 1·44, 95 % CI 1·01, 2·07). However, we found no association between 'Western' or 'potato and eggs' patterns and WHR (OR: 0·89, 95 % CI 0·62, 1·28 and OR: 1·16, 95 % CI 0·69, 1·42, respectively). None of the identified dietary patterns was associated when defining obesity with waist circumference or BMI. In conclusion, participants had a greater chance of central obesity defined based on WHR following a lunchtime pattern with a higher and positive loading factor for 'Bread, grains and fat'.

Chitosan-Raloxifene nanoparticle containing doxorubicin as a new double-effect targeting vehicle for breast cancer therapy.

BACKGROUND: treatment of breast cancer as one of the most common cancers in the world remains an important area of drug development based on nanoparticulate systems. Effective targeted therapy of affected cells based on ligand conjugate biocompatible polymeric nanoparticles is an attractive perspective in this context. OBJECTIVE: In this study, a novel double effect nanoparticle based on Chitosan-Raloxifene conjugate was prepared for adjuvant therapy (hormone and chemo therapy) and drug targeting to breast cancer cells via estrogen receptor (ER). METHODS: Chitosan-raloxifene conjugate was synthesized. Related nanoparticles containing doxorubicin (DOX) were prepared and characterized. Experimental design study was performed to determine the optimum levels of variables in the preparation of nanoparticle. Drug loading, release, nanoparticle stability, and the effect of nanoparticles on cell viability were evaluated. Further, inhibition tests were performed to demonstrate that the function of these novel nanoparticles is mediated via ER. RESULTS: Chitosan-raloxifene conjugate was successfully synthesized. The prepared nanoparticles showed sizes within 25-35 nm, more than 95% drug loading, about 60% of drug release and desired stability after 24 h. XTT assay on MCF-7 cell line illustrated that these nanoparticles could inhibit the cellular growth up to 60%. The results from inhibition tests revealed that prepared nanoparticles can inhibit cell growth via ER blocking. CONCLUSION: This study introduced chitosan-raloxifene nanoparticles containing doxorubicin as a novel targeting agent for adjuvant therapy of breast cancer. Graphical abstract.

Novel chitosan based nanoparticles as gene delivery systems to cancerous and noncancerous cells.

The present study aimed to investigate in vitro DNA transfection efficiency of three novel chitosan derivatives: thiolated trimethyl chitosan (TMC-Cys), methylated 4-N,N dimethyl aminobenzyl N,O carboxymethyl chitosan(MABCC) and thiolated trimethyl aminobenzyl chitosan(MABC-Cys). After polymer synthesis and characterization, nanoparticles were prepared using these polymers and their size, zeta potential and DNA condensing ability were measured. After that, cytotoxicity and transfection efficiency of nanocomplexes were carried out in three different cells. The results showed that all polymers could condense DNA plasmid strongly from N/P 2 and nanocomplexes had eligible sizes and zeta potentials. Moreover, the nanocomplexes had negligible cytotoxicity and MABC-Cys was the most effective vehicle for gene delivery in HEK-293T cells. In the two other cell lines, SKOV-3 and MCF-7, TMC-Cys exhibited the highest transfection efficiency. This study indicated that chemical structure of these novel chitosan derivatives in the interaction with the cell type can lead to successful gene delivery.

Characteristics of women applying for a legal abortion in the Islamic Republic of Iran.

BACKGROUND: Legal abortion has been permitted in the Islamic Republic of Iran since 2003 if there is serious and incurable disease that would cause the mother or the fetus suffering. AIMS: This study evaluated the characteristics of women applying for a legal abortion licence to the Tehran Province General Office of Legal Medicine, and compared the findings with earlier studies to evaluate changes over time. METHODS: All women visiting the office between August 2011 and 2012 to apply for a legal abortion licence were interviewed and sociodemographic data, reason for the application and outcome of the application were recorded. RESULTS: A total of 1378 women applied for a licence, and 48% were issued. Most applications (80.6%) were for fetal rather than maternal indications and 90.2% of the licences issued were for fetal indications. Most of the applications for fetal indications (53.7%) were granted a licence, while 75.7% for maternal indications were rejected. Neurological abnormalities in the fetus were the most common reason for the application (24.6%) and licences issued (30.7%). Neurological and psychological disorders were the most common maternal reason in all applications (25.7%) and in unsuccessful applications (28.6%). Cardiac disease (23.1%) was the most common maternal reason in successful applications. CONCLUSIONS: Comparison of the results with those of earlier studies shows an increase in the number of women applying for a legal abortion licence and in the number of licences issued. Similar studies are recommended to provide information on the effect of national abortion laws and help improve the legal abortion process in the Islamic Republic of Iran.

An insight into the determination of trace levels of benzodiazepines in biometric systems: Use of crab shell powder as an environmentally friendly biosorbent.

A vortex assisted dispersive solid phase extraction approach (VADSPE) based on crab shell powder as biodegradable and biocompatible µ-sorbent was developed for simultaneous analysis of three benzodiazepines (BZPs): Oxazepam, Flurazepamand Diazepam, in biological matrixes included blood, nail, hair and urine samples. The effective parameters in VADSPE process, including the volume of uptake solvent, the dosage of sorbent, extraction time and back extraction time, were optimized using response surface methodology(RSM) based on central composite design(CCD). The suggested technique allows successful trapping of BZPs in a single-step extraction. Under the optimized extraction conditions, the proposed approach was exhibited low limits of detection (0.003-1.2 µg·mL-1), an acceptable linearity (0.04-20 µg·mL-1). Method performance was assessed by recovery experiments at spiking levels of 10 µg·mL-1(n = 5) for BZPs in blood, nail, hair and urine samples. Relative recoveries were determined by HPLC, which were between 36%and 95.6%.

Biocompatible electrospinning chitosan nanofibers: A novel delivery system with superior local cancer therapy.

In this study, an electrospinning technique was used for the fabrication of novel biomedicated nanofibers which are applied for preventing wound infections and local chemotherapy. CURs containing nanofibers with a crosslinking agent (Si-O-Si network) have been produced through functionalization of graphene oxide with APTES. In vitro drug release profile results showed the novel nanofibers could limit the drug's initial burst release and provide better sustainability in comparison with the blend nanofibers without modified GO. The novel delivery vehicle can inhibit the growth of MRSA and S. epidermidis up to 94% and 88%. Also in vitro cell toxicity experiments which were performed by XTT method on MCF-7, HEP G2 and L929 cell lines showed that anticancer activity of CUR remained intact even after loading into nanofibers. This result suggested that the fGO-Si-CUR including nanofibers were a promising candidate for postoperative chemotherapy.

Thiolated methylated dimethylaminobenzyl chitosan: A novel chitosan derivative as a potential delivery vehicle.

Chitosan is a natural mucoadhesive, biodegradable, biocompatible and nontoxic polymer which has been used in pharmaceutical industry for a lot of purposes such as dissolution enhancing, absorption enhancing, sustained releasing and protein, gene or drug delivery. Two major disadvantages of chitosan are poor solubility in physiological pH and low efficiency for protein and gene delivery. In this study thiolated methylated N-(4-N,N-dimethylaminobenzyl) chitosan was prepared for the first time in order to improve the solubility and delivery properties of chitosan. This novel chitosan derivative was characterized using 1H NMR, Ellman test, TGA and Zetasizer. Cell toxicity studies were performed on Human Embryonic Kidney 293 (Hek293) cell line using XTT method, to investigate the potential effect of this new derivative on cell viability. 1H NMR results showed that all substitution reactions were successfully carried out. Zeta potential of new derivative at acidic and physiological pHs was greater than chitosan and it revealed an increase in solubility of the derivative. Furthermore, it had no significant cytotoxicity against Hek293 cell line in comparison to chitosan. These findings confirm that this new derivative can be introduced as a suitable compound for biomedical purposes.

Synthesis of raloxifene-chitosan conjugate: A novel chitosan derivative as a potential targeting vehicle.

Chitosan is a biocompatible, non-toxic and biodegradable biopolymer. Due to the presence of functional groups on its surface, it can be modified and used as a carrier in targeted drug/gene delivery systems. In this study, raloxifene (a selective estrogen receptor ligand) was conjugated to chitosan using different methods. The conjugates were investigated by means of FTIR, TGA and physical properties assessments. Cell viability was evaluated by XTT assay. FTIR and TGA results confirmed that the conjugation between chitosan and raloxifene occurred more efficiently when trimethyl chitosan in the presence of triethylamine and excess amount of linker was used. XTT assay on MCF-7 cell line illustrated that more than 80% of cells were viable after 24h exposure to selected molecules. These findings confirm that the conjugation of raloxifene-chitosan can occur successfully using special synthesis condition and this novel chitosan derivative can be introduced as a potential drug/gene targeting agent.

Neglected role of hookah and opium in gastric carcinogenesis: a cohort study on risk factors and attributable fractions.

A recent study showed an association between hookah/opium use and gastric cancer but no study has investigated the relationship with gastric precancerous lesions. We examined the association between hookah/opium and gastric precancerous lesions and subsequent gastric cancer. In a population-based cohort study, 928 randomly selected, healthy, Helicobacter pylori-infected subjects in Ardabil Province, Iran, were followed for 10 years. The association between baseline precancerous lesions and lifestyle risk factors (including hookah/opium) was analyzed using logistic regression and presented as odds ratios (ORs) and 95% confidence intervals (CIs). We also calculated hazard ratios (HRs) and 95% CIs for the associations of lifestyle risk factors and endoscopic and histological parameters with incident gastric cancers using Cox regression models. Additionally, the proportion of cancers attributable to modifiable risk factors was calculated. During 9,096 person-years of follow-up, 36 new cases of gastric cancer were observed (incidence rate: 3.96/1,000 persons-years). Opium consumption was strongly associated with baseline antral (OR: 3.2; 95% CI: 1.2-9.1) and body intestinal metaplasia (OR: 7.3; 95% CI: 2.5-21.5). Opium (HR: 3.2; 95% CI: 1.4-7.7), hookah (HR: 3.4; 95% CI: 1.7-7.1) and cigarette use (HR: 3.2; 95% CI: 1.4-7.5), as well as high salt intake, family history of gastric cancer, gastric ulcer and histological atrophic gastritis and intestinal metaplasia of body were associated with higher risk of gastric cancer. The fraction of cancers attributable jointly to high salt, low fruit intake, smoking (including hookah) and opium was 93% (95% CI: 83-98). Hookah and opium use are risk factors for gastric cancer as well as for precancerous lesions. Hookah, opium, cigarette and high salt intake are important modifiable risk factors in this high-incidence gastric cancer area.

Serum ghrelin; a new surrogate marker of gastric mucosal alterations in upper gastrointestinal carcinogenesis.

BACKGROUND: A few studies have indicated inverse relationships between serum ghrelin and gastric and esophageal cancers but those associations have been restricted to specific populations, including smokers and overweight individuals. We examined the association between ghrelin and gastroesophageal cancers and atrophic gastritis in a population-based setting. METHODS: In total 220 gastroesophageal cancers, comprising non-cardia and cardia gastric cancer, esophageal adenocarcinoma, esophageal squamous cell carcinoma (SCC) and age and gender-matched controls were recruited. Serum ghrelin, pepsinogen I/II ratio (PGI/II) and anti-H.pylori IgG antibodies were measured. Relationships between ghrelin and gastroesophageal cancers, after adjustment for PGI/II ratio, H.pylori status and smoking, were tested using logistic regression. Furthermore, in 125 endoscopically normal volunteers, with and without histological atrophic gastritis, the relationship with ghrelin was compared. RESULTS: Serum ghrelin (lowest vs. highest quintile) was inversely associated with gastric cancer: OR (95% CI) 8.71 (1.70-44.59) for cardia and 6.58 (1.26-34.46) for non-cardia cancer. Lower serum ghrelin was also associated with esophageal SCC: OR (95% CI) 5.69 (1.36-23.78), but not with esophageal adenocarcinoma. A similar association was observed between gastric cancer (cardia and non-cardia) and esophageal SCC when serum ghrelin was analysed as a continuous scaled variable. In endoscopically-normal volunteers, extensive atrophic gastritis was associated with low serum ghrelin [OR (95% CI) 0.25 (0.10-0.64)]. CONCLUSION: Inverse associations between ghrelin and some gastroesophageal cancers suggest a potential role for serum ghrelin as a biomarker of upper gastrointestinal cancers and atrophic gastritis. In areas with a high incidence of gastric and/or esophageal cancer, screening might be more effectively targeted to individuals with low serum ghrelin in addition to the PGI/II ratio.

Gastric cancer mortality in a high incidence area: long-term follow-up of Helicobacter pylori-related precancerous lesions in the general population.

BACKGROUND: Due to a lack of clear criteria for recognizing subjects at risk of progression to gastric cancer (GC), this cohort study seeks to identify predictors of GC death in a high-risk population. METHODS: During 2000-2001, 1011 randomly selected residents of Ardabil, Iran without a history of gastrointestinal diseases, underwent upper endoscopy with targeted biopsy sampling. Until 2013, cancer mortality data were obtained using cancer and death registry data and verbal autopsy reports. Cox regression was used to estimate hazard ratios (HR). RESULTS: A total of 3.95% of the participants [mean age: 53.1 ± 9.9 years, 49.8% males, and 88.2% Helicobacter pylori (H. pylori-positive)] died of GC. In the multivariate model, precancerous lesions at the beginning of follow-up were associated with increased GC mortality. The HR [95% confidence interval (CI)] was 7.4 (1.6-33.8) for atrophic gastritis (AG) and 23.6 (5.5-102.3) for intestinal metaplasia (IM). Age over 50 (HR = 4.4; 1.3-14.2), family history of GC (HR = 6.8; 3.3-13.8), smoking (HR = 7.4; 3.2-17.3), and endoscopically confirmed gastric ulcer (GU, HR = 6.5; 2.5-16.4) were independently associated with GC mortality. The concomitant presence of a precancerous lesion increased the HR to 46.5 (10.8-198.6) for a family history of GC, 27.6 (6.5-116.4) for smoking, and 25.1 (6.3-105.3) for age >50 years. CONCLUSIONS: In this population with a high rate of H. pylori infection, age over 50 years, smoking, family history of GC, IM, AG, and in particular, an undiagnosed GU were significant independent risk factors for mortality due to GC. The assessment of a combination of these risk factors might identify individuals at risk of GC who could possibly benefit from regular surveillance.

Rational design of heteropolyacid-based nanosorbent for hollow fiber solid phase microextraction of organophosphorus residues in hair samples.

A novel heteropolyacid-based supported ionic liquid (IL) mediated sol-gel hybrid organic-inorganic material is presented for effective use in hollow fiber solid phase microextraction (HF-SPME). We examined a Keggin-based IL that was evaluated in conjunction with sol-gel. This study shows that Keggin-based IL sol-gel generated porous morphology pro effective extraction media. The method was developed for the extraction of the organophosphorus pesticides (OPs); diazinon, fenitrothion and malathion from human hair samples. The OPs were subsequently analyzed with high performance liquid chromatography and photodiode array detection (HPLC-PDA). In the basic condition (pH 10-11), the gel growth process in the presence of IL was initiated. Afterward, this sol was injected into a polypropylene hollow fiber segment for in situ-gelation process. Parameters affecting the efficiency of HF-SPME were thoroughly investigated. Linearity was observed over a range of 0.02-50,000 µg/g and 0.0001-25,000 ng/mL with detection limits between 0.0074-1.3000 µg/g and 0.00034-0.84 ng/mL for the OPs in hair and aqueous matrices, respectively. The relative recoveries in the real samples, for OPs in the storekeeper hair ranged from 86 to 95.2%.

Ionic liquid mediated sol-gel sorbents for hollow fiber solid-phase microextraction of pesticide residues in water and hair samples.

An ionic liquid mediated sol-gel sorbents for hollow fiber solid-phase microextraction (HF-SPME) was developed for extraction of the pesticides: diazinon, fenitrothion, malathion, fenvalerate, phosalone and tridemorph from human hair and water samples. The analytes were subsequently analyzed with high performance liquid chromatography and diode array detection (HPLC-DAD). Preliminary experiments were carried out in order to study experimental conditions for pesticides' extraction from spiked hair and water samples with HF-SPME using hollow fiber-supported ionic liquid mediated sol-gel sorbent. The sol-gel nanocomposites were reinforced with nanoparticles such as carboxylic functionalized multi-walled carbon nanotubes (COOH-MWCNTs), amino functionalized multi-walled carbon nanotubes (NH(2)-MWCNTs), nano SiO(2), nano TiO(2) and nano MgO comparatively to promote extraction efficiency. In this device, the innovative solid sorbents were developed by the sol-gel method via the reaction of tetraethylorthosilicate (TEOS) with 2-amino-2-hydroxymethyl-propane-1,3-diol (TRIS). In the basic condition (pH 10-11), the gel growth process in the presence of ionic liquid and nanoparticles was initiated. Then, the sol was injected into a polypropylene hollow fiber segment for in situ gelation process. Parameters affecting the efficiency of HF-SPME were thoroughly investigated. Linearity was observed over a range of 0.01-25,000 ng/mL with detection limits between 0.004 and 0.095 ng/mL for the pesticides in the aqueous matrices and 0.003-0.080 ng/mL in the hair matrices. The relative recoveries in the real samples ranged from 82.0% to 94.0% for the pesticides store seller's hair and the work researchers' hair. Results are showing the great possibilities of HF-SPME-HPLC-PDA for analysis of pesticides in biological and environmental samples.

Gastric cancer in Ardabil, Iran--a review and update on cancer registry data.

The incidence rate of gastric cancer in western countries has shown a remarkable decline in recent years while it is still the most common cancer among men in Iran. Ardabil, a North Western province, was found to have the highest rate of GC in Iran and one of the highest gastric cardia cancer rates in the world. We used the most recent data from Ardabil cancer registry to update on the incidence and mortality of GC and performed an extensive search of the English and Persian literature in Pub Med, Embase and all 5 Persian web-based databases, respectively, to summarize all possible risk factors for GC in Ardabil. The age-standardized incidence rate of gastric cancer was 51.8 (95% CI: 47.8-55.8) in men and 24.9 (95% CI: 21.5-27.2) in women per 100,000. Age-standardized mortality rates for gastric cancer in this population were 32.2 (95% CI: 29.1-35.3) and 16.3 (95% CI: 13.9-18.6). The gastric cardia sub-site was the most common location (32.7%) in Ardabil. According to our review H.pylori infection, gastroesphageal reflux symptoms, tobacco smoking, and high intakes of salt, red meat and dairy products increase the risk of GC while diets with a high content of allium vegetables and fruits, especially citrus fruits, and consumption of fresh fish, were significantly protective against GC. We conclude that Ardabil has the highest rate of GC in Iran and one the highest rates of gastric cardia cancer in the world, with no evidence of decline in incidence since 2000. In addition to H.pylori infection, the epidemic of gastroesphageal reflux disease and several dietary factors may be responsible for the very high incidence of gastric cardia cancer in Ardabil.