najmeh ranji

 Acinetobacter baumannii, a gram-negative pathogen, is recognized as a healthcare-associated opportunistic pathogens. In this study, the in vitro antibacterial properties of margatoxin (MgTX) were investigated against clinical isolates.

The drug resistance profile of five antibiotics: piperacillin (100μg), imipenem (10μg), ceftazidime (30μg), amikacin (30μg), and ciprofloxacin (5μg) were evaluated with disc diffusion (Kirby-Bauer) method in 20 clinical isolates. Biofilm formation was assessed using the microtiter plate assay. Synergistic effects of MgTX in combination with ciprofloxacin was evaluated.

Our results showed that the resistance to all antibiotics was ≥90%. All isolates had ability of biofilm formation (moderate to strong). Checker board method confirmed synergistic effect between MgTX and ciprofloxacin. indicated that a dose-dependent suppression of bacterial growth was achieved with the combined use of MgTX and ciprofloxacin.

 It seems that MgTX, with antibacterial properties, can use in therapeutic strategies in future against antibiotic resistant isolates.

Matrix metalloproteinases (MMPs) as MMP2 and MMP9 degrade extracellular matrix. Lead (Pb) is a well-known environmental contaminant which could impair the activity of MMPs. The aim of this study was to investigate the effects of N-acetylcysteine, as an antioxidant, on the expression of MMP2 and MMP9 genes in the liver of rats exposed with Pb.

In this study, the 30 male rats were randomly divided into five groups(n=6): 1) control, 2) acute dose of Pb (70 mg/kg), 3) acute dose of Pb (70 mg/kg) + continuous administration of NAC (50 mg/kg), 4) chronic dose of Pb (2 mg/kg), and 5) chronic dose of Pb (2 mg/kg) + continuous administration of NAC (50 mg/kg). Acute dose of Pb was administrated on the first day of study and chronic dose of Pb and Continuous administration of NAC was used every day for 4 weeks as gavage. Hematoxylin and eosin (H&E) staining was used to study histopathological changes. The expression of MMP2 and MMP9 genes was evaluated using Quantitative RT-PCR

In the liver of rats exposed with Lead (Pb) especially at chronic dose, was observed structural abnormality and increased inflammatory. Q-RT-PCR analysis showed the expression of MMP2a and MMP9 genes increased in Pb exposed liver and decreased in NAC administrated liver after Pb exposure.

Our results suggest that NAC can protect the liver of rats through downregulation of metalloproteinases after Pb exposure and decrease inflammation and tissue damage.

Curcumin, a natural product of turmeric, is known for its antibacterial and antifungal properties. Candida albicans is a major fungal pathogen with high mortality rate, particularly in immunocompromised patients. This study aimed to evaluate the effect of curcumin encapsulated in nanoparticles (polymersomes) in combination with fluconazole on the expression of the MDRI gene in drug-resistant isolates of C. albicans. This descriptive cross-sectional study involved obtaining 50 clinical samples, from women with vulvovaginal infections at Al-Zahra hospital (Rasht, Iran). After identifying the strains, resistance to fluconazole was assessed using disc diffusion and broth dilution methods. Six fluconazole-resistant isolates of C. albicans were treated with ½ MIC fluconazole (control) alone and in combination with curcumin encapsulated in nanoparticles. After 24 hours, the two cell groups were cultured on Sabouraud dextrose agar (SDA) to estimate the cell death rate. The expression of the MDR1 gene was quantitatively investigated using the qRT-PCR method in treated and untreated isolates. Our finding indicated that combined therapy with ½ MIC fluconazole and curcumin encapsulated in nanoparticles (at a concentration of 400µg/ml) reduced fungal growth by up to 50% within during 24 hours. In treated cells, qRT-PCR analysis revealed a decrease in MDR1 gene expression compared to untreated cells. Curcumin appears to enhance the effectiveness of fluconazole in fluconazole-resistant isolates by reducing MDR1 gene expression.

MicroRNAs (miRNAs) are a class of small non-coding RNAs (17-25 nucleotides) that have been studied in many diseases. miRNAs studies in different cancers have shown that miRNAs may be considered oncogene or tumor suppressor. So far, many studies have shown that miR-17-5p and miR-93-5p are important regulatory molecules in some biological processes, such as cell proliferation, associated with cancer formation. This study aimed to investigate and compare the tissue and plasma expression levels of miR-17-5p and miR-93-5p in patients with ductal carcinoma breast cancer with the normal control group.

The total RNA (including miRNA) was extracted from breast and plasma tissue samples of cancerous and normal samples. The RNA concentration and purity were confirmed using optical absorbance measurements. cDNA was synthesized, and the expression levels of miR-17-5p and miR-93-5p were assessed semi-quantitatively by SYBR Green-based real-time RT-PCR assay in plasma and breast tissues of ductal carcinoma breast cancer compared with the control normal samples with SNORD47 as internal normalizer. Data were statistically evaluated using GraphPad Prism 8.0.2.

This study was approved by the Ethics Committee of the institute (IRAN 52d/4922, 6.10.2016). All study individuals signed a consent form to use their clinical samples and personal data under the physician’s supervision.

The expression level of miR-17-5p showed significantly higher expression in tissues and plasma of the cancer group compared with the control group (P<0.0001). It was also significantly associated with tumor stage and lymph node, and ER (estrogen receptor) and PR (progesterone receptor) status (P<0.0001). While decreased expression of miR-93-5p in plasma and tumor tissues was shown to be significantly associated with tumor stage and lymph node involvement (P<0.0001).

The data revealed that high expression of miR-17-5p and low expression of miR-93-5p in both plasma and breast tumor might be associated with poor prognosis in breast cancer. However, miR-17-5p, due to the greater change in expression and ease of plasma detection, may serve as a possible non-invasive biomarker for breast cancer’s poor prognosis. Further follow-up studies are required to confirm this finding.

Colorectal Cancer (CRC) is the most common malignant gastrointestinal cancer. Cancer stem cells (CSCs) are the major cause of cancer recurrenceand cancer drug resistance. Silibinin, as an herbal compound, has anticancer properties.

The present study aimed to evaluate the antiproliferative effects of silibinin on HT29 stem-like cells (spheroids).

In this study, antiproliferative and apoptotic properties of Silibinin encapsulated in Polymersome Nanoparticles (SPNs) were evaluated by MTT assay, propidium iodide(PI)/AnnexinV assay, cell cycle analysis, and DAPI (4',6-diamidino-2-phenylindole) staining. The expression of some miRNAs and their potential targets was evaluated by real-time reverse transcription-polymerase chain reaction (qRT-PCR).

IC50 of SPNs was determined at 28.13±0.78μg/ml after 24 h. SPNs (28μg/ml) induced apoptosis by 32.36% in HT29 cells after 24 h. DAPI staining indicated a decrease instained nuclei after SPNs induction.SPNs treatment increased the expression of miR-34a, as well as P53, BAX, CASP9, CASP3, and CASP8. The downregulation of miR-221 and miR-222 was observed in SPNs treated cells. Moreover, SPNs decrease the expression level of CD markers inHT29 spheroids (cancer stem cells) compared to untreated spheroids.Spheroids were completely destroyed after 72 h treatment with SPNs (28μg/ml).

As evidenced by the obtained results, SPNs can be used as an effective anticancer agent in multi-layer (cancer stem cells) and mono-layer cancerous cells with the upregulation of tumor suppressive miRs and genes, as well as downregulation of oncomiRs and oncogenes.

Gastric cancer is the sixth most frequent malignancy and the fourth leading cause of cancer death in the world with poor survival rate. Early detection may increase patient’s survival and reduce mortality. miRNAs are small non-coding RNAs which function as negative regulators of genes expression in post-transcriptional level. The aim of this study was to evaluate the expression of miR-34a and miR-375 in the plasma of gastric cancer patients in Guilan province.Methods and materials: In this study, 25 gastric cancer patients and 25 healthy individuals in Guilan province during 2018-2019 were enrolled. The expression of miR-34a and miR-375 was evaluated in plasma of patients with Gastric cancer and healthy individuals by Q-RT-PCR method. The correlation between their expression and patient’s clinicopathological characteristics was also investigated. ROC curve analysis of the miRNAs was performed.

There was no significant difference in the plasma level of miR-34a and miR-375 in gastric cancer patients compared to control. There was no significant difference between the the plasma level of miR-34a and miR-375 and clinicopathological features of patients. Area under the curve (AUC) value of ROC analysis for miR-34a was 0.56±0.08 (P=0.42). Area under the curve (AUC) value of ROC analysis for miR-375 was 0.62±0.08 (P=0.14).

Our results suggested that miR-34a and miR-375 probably don’t be appropriate biomarkers for diagnosis of gastric cancer in Guilan province.

The increasing trend of cancer morbidity and mortality is a major human health concern, indicating the necessity for the design and introduction of novel anticancer compounds. The use of nanotechnology products is a new approach to cancer treatment. Therefore, the current study was performed to synthesize Titanium Dioxide nanoparticles (NPs) functionalized with glutamine and conjugated to Thiosemicarbazide (TiO2@Gln-TSC) to inhibit the proliferation of liver cancer cells line (HepG2) and evaluate the effect of TiO2@Gln-TSC NPs on the expression of apoptotic genes.

TiO2@Gln-TSC NPs were synthesized by a chemical method and characterized by Fourier-transform infrared spectroscopy (FT-IR), Energy-dispersive X-ray spectroscopy (EDS), Scanning electron microscopy (SEM), and Transmission electron microscopy (TEM). The cytotoxicity of the Titanium Dioxide nanoparticles was evaluated by the MTT assay, and relative gene expression was studied by Real Time PCR method.

The results showed that the synthesized Titanium Dioxide nanoparticles were spherical with a size range of 59 to 82 nm. The particles had a considerable anti-proliferative effect on liver cancer cells line with IC50 of 80 µg/mL. The treatment of the cancer cell line with TiO2@Gln-TSC NPs significantly increased the expression of the CASP3, BAX, and BCL2 by 2.8, 2.7, and 1.3 folds, respectively, which indicated the activation of apoptotic pathways in the treated cells.

The results showed that the TiO2@Gln-TSC NPs could inhibit the proliferation of liver cancer cells line and by triggering the apoptosis pathway.

Organic meat products are well known for their probiotic values due to the presence of probiotic lactic acid bacteria such as Lactobacillus, Leuconostoc, Lactococcus, and Pediococcus strains. The present study aimed to isolate and characterize new strains of lactic acid bacteria (LABs) from organic meat sausages and evaluate their antimicrobial activities.

In this study, LAB strains were isolated from vacuum-packed organic meat sausages bought from Solico Group Co Ltd. (Tehran, Iran). All isolates were characterized by morphological, biochemical, and 16S rRNA analysis. The primary antibacterial activity of the isolates was evaluated against Micrococcus luteus PTCC 1408. The growth kinetics and antimicrobial activity of the strain MN-B against Lactobacillus casei ATCC 39392 were determined in an MRS broth medium. In addition, a bacteriocin produced by the strains MN-B revealed antimicrobial activity against selected foodborne pathogens. Bacteriocin produced by the MN-B strain was partially purified using the adsorption-desorption method followed by dialyzes.

In this study, two Pediococcus spp. and three Leuconostoc spp. with antimicrobial activity were isolated from vacuum-packed organic meat sausages and designated as MN-A, MN-B, MN-A2, MN-A2-1, and MN-A3. The results showed that the isolate MN-A and MN-B belonged to the strain Pediococcus acidilactici and the MN-A2, MN-A2-1, and MN-A3 isolates were identified as Leuconostoc mesenteroides strains. Amongst the isolates, the strain MN-B showed the highest antimicrobial activity against the Micrococcus luteus PTCC 1408. The molecular weight of bacteriocin was about 5.0 KDa.

Pediococcus acidilactici (strain MN-B) showed significant antimicrobial activity against Salmonella enterica subsp. enterica serotype Typhimurium PTCC 1709, Staphylococcus aureus PTCC 1113, Listeria monocytogenes PTCC1302, and Listeria inovani PTCC 1303. Therefore, this strain can be considered a potential candidate in different sectors such as the food industry as a preservative.

The first vital stage in the developmental program occurs at the time before implantation, after  fertilization, and before implantation of the fetus in the uterus. This period represents a vulnerable stage because the epigenome undergoes dynamic changes in DNA methylation profiles. Changes in early embryonic reprogramming can disrupt DNA methylation patterns and cause permanent changes in the growth program, leading to the onset of adverse health outcomes in offspring. Although there are many evidences that exposure to harmful substances during embryonic development before implantation can cause lasting epigenetic changes in offspring, the mechanisms are not yet fully understood. Since the physiological or pathological changes in DNA methylation can occur in response to environmental cues, a suitable environment plays an important role in fetal growth success. In this review article, we investigated the mechanisms involved in fetal epigenetic reprogramming during DNA methylation and maternal environmental stressors, such as the effects of paraquat herbicide during the pre-implantation stages of the embryo.

Urinary tract infection (UTI) is one of the common infections in children which is rapidly acquiring more and more resistance to antimicrobial drugs in the worldwide. The aim of this study was to evaluate the frequency of SHV, TEM and CTX-M genes in Escherichia Coli and Klebsiella Pneumoniae strains isolated from UTI in children in 17 Shahrivar hospital from Rasht city, Iran.

In this descriptive cross-sectional study, 49 strains of Escherichia Coli and Klebsiella Pneumoniae were isolated from 17 Shahrivar hospital from Rasht city and identified by biochemical tests. The resistance and susceptibility of the strains to antibiotics was determined by both Kirby Bauer and Broth dilution methods. To evaluate frequency of SHV, TEM, and CTX-M genes in the isolates, the PCR method was used. To statistical analysis, χ2 test was used with SPSS software version 19.

In this study, the most resistance was observed to Ceftriaxone (88.9%) and ampicillin (81.5%) in Escherichia Coli and to ampicillin (95.5%) and Ceftriaxone (77.3%) in Klebsiella Pneumoniae. Of 49 isolates, 89.8% had SHV gene, 89.8% had CTX-M gene, and 100% had TEM gene.

We concluded that one of the reasons of increasing multi drug resistance in nosocomial isolates of UTI in Rasht may be an increase in horizontal transfer of plasmid genes between these isolates.

MicroRNAs (miRNAs) are a class of small non-coding RNAs (17-25 nucleotides) that have been studied in many diseases. miRNAs studies in different cancers have shown that miRNAs may be considered oncogene or tumor suppressor. So far, many studies have shown that miR-17-5p and miR-93-5p are important regulatory molecules in some biological processes, such as cell proliferation, associated with cancer formation. This study aimed to investigate and compare the tissue and plasma expression levels of miR-17-5p and miR-93-5p in patients with ductal carcinoma breast cancer with the normal control group.

The total RNA (including miRNA) was extracted from breast and plasma tissue samples of cancerous and normal samples. The RNA concentration and purity were confirmed using optical absorbance measurements. cDNA was synthesized, and the expression levels of miR-17-5p and miR-93-5p were assessed semi-quantitatively by SYBR Green-based real-time RT-PCR assay in plasma and breast tissues of ductal carcinoma breast cancer compared with the control normal samples with SNORD47 as internal normalizer. Data were statistically evaluated using GraphPad Prism 8.0.2.

This study was approved by the Ethics Committee of the institute (IRAN 52d/4922, 6.10.2016). All study individuals signed a consent form to use their clinical samples and personal data under the physician’s supervision.

The expression level of miR-17-5p showed significantly higher expression in tissues and plasma of the cancer group compared with the control group (P<0.0001). It was also significantly associated with tumor stage and lymph node, and ER (estrogen receptor) and PR (progesterone receptor) status (P<0.0001). While decreased expression of miR-93-5p in plasma and tumor tissues was shown to be significantly associated with tumor stage and lymph node involvement (P<0.0001).

The data revealed that high expression of miR-17-5p and low expression of miR-93-5p in both plasma and breast tumor might be associated with poor prognosis in breast cancer. However, miR-17-5p, due to the greater change in expression and ease of plasma detection, may serve as a possible non-invasive biomarker for breast cancer’s poor prognosis. Further follow-up studies are required to confirm this finding.

Cadmium has similar chemical and physical properties to metals such as zinc and copper, can be transferred to cells via an ionic and molecular process, and disrupts cell biological functions and homeostasis. The aim of this study was to investigate the effect of cadmium chloride on serum and tissue levels of zinc and copper, Also, the protective role of N-acetylcysteine (NAC) in preventing cadmium-induced toxicity and tissue inflammation in the lung tissue of rats exposed to single-dose and continuous-dose cadmium.

30 male Wistar rats were randomly divided into five groups of six in this interventional-experimental study. The control group only received regular water and food. The first group received a single dose treatment of 80 mg/kg of cadmium chloride on the first day of the study, while the second group received a continuous dose of 2.5 mg / kg of cadmium chloride every other day for 4 weeks.  On the first day of the study, the third group received a single dose of 80 mg / kg cadmium chloride along with 50 mg / kg N-acetylcysteine. For four weeks, the fourth treatment group received a continuous dose of 2. 5 mg of cadmium chloride along with 50 mg of N-acetylcysteine. Cadmium chloride and N-acetylcysteine were administered to the animals via gavage. At the end of the treatment period, blood samples from the heart were taken to determine the level of the elements. After anesthesia, lung tissue was removed from the chest and part of it was used for histological work, while the other part was used to measure element levels.

Treatment with cadmium chloride showed a decrease in serum copper levels in the second treatment group compared to the control group (P-value <0.01). In addition, cadmium chloride treatment in the second treatment group compared to the control group caused a significant reduction in copper tissue level (P-value <0.001). Cadmium chloride treatment reduced serum zinc levels in the second treatment group compared to the control group (P-value <0.01). Tissue level of zinc in the second treatment group compared to the control showed a significant decrease (P-value <0.001). Simultaneous treatment of cadmium chloride and N-acetylcysteine ​​in the fourth treatment group as a continuous dose compared to the second treatment group caused a significant increase in serum copper level (P-value <0.05). And copper tissue level in the fourth treatment group increased significantly compared to the second treatment group (P-value <0. 001). Also, simultaneous treatment of cadmium chloride and N-acetylcysteine ​​in the fourth treatment group showed that serum zinc level (P-value <0.05) and tissue level of zinc (P-value <0.01) were significantly higher than the second treatment group.

Continuous N-acetylcysteine administration reduces the toxicity of cadmium chloride in rats exposed to a continuous dose of cadmium chloride and improves serum and tissue copper and zinc levels.

Cadmium is a toxic heavy metal found in environmental pollutants in metropolitan areas that enters the body via inhalation and causes the production of reactive oxygen species, apoptosis, and changes in protein structure. The purpose of this study was to see how N-acetyl cysteine (due to its sulfhydryl group and purification of reactive oxygen species) affected liver enzymes and inflammation in rats exposed to acute and chronic cadmium chloride doses.

In this study, 30 two-month-old male Wistar rats were randomly divided into 5 groups of 6. The control group (G1) was fed only standard water and food and the first treatment group (G2) received 80 mg / kg cadmium chloride on the first day of the study. The second treatment group (G3) received 2.5 mg / kg cadmium chloride daily for four weeks. The third treatment group (G4) received 80 mg / kg cadmium chloride along with 50 mg / kg n-acetyl cysteine ​​on the first day of the study. The fourth treatment group (G5) received 2.5 mg / kg cadmium chloride and 50 mg / kg N-acetyl cysteine ​​daily for four weeks. At the end of the treatment period, after anesthesia, blood samples were taken from the hearts of rats to measure the level of liver enzymes. Then their liver was removed and histopathological tests were performed.

Treatment with cadmium chloride in continuous dose caused a significant increase in the levels of ALT, AST, ALP and LDH enzymes compared to the control group. There was no significant change in GGT enzyme level. Cadmium chloride caused inflammation around the arteries and increased the thickness of the hepatic arteries. After treatment with N-acetyl cysteine ​​in the fourth treatment group (G5), the level of enzymes compared to the second treatment group (G3) showed a significant decrease. Inflammation around the arteries and the thickness of the arteries were also reduced compared to G3.

Continuous N-acetyl cysteine administration reduces cadmium chloride toxicity in rats exposed to a continuous dose of cadmium chloride by lowering serum levels of ALT, AST, ALP, and LDH enzymes, as well as hepatitis.

VNTR alleles in the phenylalanine hydroxylase (PAH) gene are used for carrier detection and prenatal diagnosis in phenylketonuria families. The aim of this study was to investigate linkage between VNTR alleles and the PAH gene mutations in PKU patients in Guilan province, Iran.

In this descriptive cross-sectional study, 19 unrelated PKU patients from 17 Shahrivar children hospital in Rasht were enrolled. Genomic DNA was extracted from blood samples of PKU patients. Amplification of gene fragments was carried out by PCR method and underwent direct sequencing.

Our analysis showed that PKU patients in Guilan province had VNTR3/VNTR3, VNTR3/VNTR7, ND/VNTR7, VNTR7/VNTR7, and VNTR8/VNTR8 genotypes in PAH gene. The frequencies of VNTR3, VNTR7, and VNTR8 alleles were 21.05%, 28.94%, and 47.4%, respectively. Length of one allele was not determined (ND) by frequency 0.03%. The linkage between was observed in some mutations of PAH gene such as R400K, R261X, R261Q, IVS4+5G>T و and IVS10-11G>A with VNTR allelels PKU patients.

VNTR3, VNTR7, and VNTR8 alleles can be considered as useful marker in determining PKU carriers in Guilan. Furthermore, Genetic heterogeneity and geographic variation may be the cause of correlation of different mutations with VNTR alleles in PAH gene in Guilan province.

Lead (Pb) is a toxic heavy metal which causes adverse health effects on humans and animals. N-acetylcysteine (NAC), as an antioxidant agent, decreases tissue damages and inflammations. The aim of this study was to evaluate the effects of N-acetylcysteine on the expression of IL-10 and TGF-β genes in the lung of rats exposed to Pb.

In this interventional quasi-experimental study, the rats were randomly divided into 5 groups, including 1) control, 2) acute dose of Pb, 3) acute dose of Pb + continuous administration of NAC, 4) chronic dose of Pb, and 5) chronic dose of Pb + continuous administration of NAC. Acute dose of Pb (70 mg/kg) was administrated on the first day of the study. Chronic dose of Pb (2 mg/kg) and Continuous administration of N-acetylcysteine (50 mg/kg) was used every day for 4 weeks. Both N-acetylcysteine and Pb were dissolved in sterile water and administrated to rats orally by gavage. Histopathological analysis was performed by tissues staining with hematoxylin-eosin (H&E). qRT-PCR method and one-Way ANOVA statistical tests with a significant level of P<0.05 were used to evaluate the expression of IL-10 and TGF-β genes.

Pb induced inflammation in acute and chronic doses. qRT-PCR analysis showed a significant decrease in IL-10 and a significant increase in TGF-β expressions. However, administration of NAC with Pb led to a decrease in inflammation by upregulation of IL-10 and downregulation of TGF-β genes in the lungs of rats.

Our results suggest that N-acetylcysteine can protect the lungs against Pb toxicity by reducing inflammation.

The aim of this experimental study was to investigate the effect of cadmium (Cd) on the expression of matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 2 (TIMP2) genes and to investigate the protective role of N-acetylcysteine ​​(NAC) on cadmium toxicity in the liver tissue of rats. In this study, male Wistar rats were randomly divided into 5 groups: control (G1), single dose of cadmium (80 mg/kg) (G2), continuous dose of cadmium (2.5 mg/kg) (G3), Single dose of cadmium (80 mg/kg) and continuous dose of NAC (50 mg/kg) (G4) and continuous dose of cadmium (2.5 mg/kg) and continuous dose of NAC (50 mg/kg) (G5). Hematoxylin and eosin (H&E) staining was used to study histopathological changes. Cadmium concentration was measured by graphite furnace spectroscopy in the liver samples. The expression of MMP9 and TIMP2 genes was evaluated using RT-PCR. Cadmium exposure, especially at continuous dose, was associated with severe tissue damage and increased inflammatory cells in the liver. The mean tissue of cadmium concentration was significantly increased by 27% (P<0.05) in the G2 group and 60% (P<0.01) in G3 group. NAC treatment in G4 group (P<0.01) and G5 group (P<0.01) significantly reduced the tissue concentration of cadmium. Cadmium also increased the expression of MMP9 gene (P<0.001) and TIMP2 gene (P<0.01) in G2 and G3 groups. NAC treatment significantly reversed these effects. Our results suggested that NAC protects liver cells by decreasing the accumulation of cadmium and reducing the expression of TIMP2 and MMP9 genes.

Gastric cancer is the fourth most common cancer in the world and Ardabil province is in the top ranks in the world. MicroRNAs are non-coding RNA molecules with a length of 18 to 21 nucleotides and due to their regulatory role in post- transcriptional gene expression; single nucleotide polymorphisms (SNPs) could affect their function on target genes regulation.

Genomic DNA was extracted from peripheral blood of 150 healthy volunteers, which were born and living in Ardabil province, 30 SNPs in microRNA genes have been detected by the Whole Exome Sequencing assay. Then, the obtained results were evaluated using Sanger-based PCR-Sequencing method. The Pearson correlation test was used for finding significant relationships.

After confirming the WES results, the population frequency of the selected variants was compared with the general populations of Iran, Europe and the world. Based on the age-standardized rate (ASR), six variants with significant differences, including rs10061133, rs12220909, rs12983273, rs2292832, rs2505901 and rs6505162 were observed.

According to the previous case-control studies which indicate the association between the variants rs10061133, rs12220909, rs12983273, rs2505901, and rs6505162 and gastric carcinogenesis in various populations, the observed significant differences in our population could imply on the presence of the cancer susceptibility in Ardabil province.

 Prostate Cancer (PCa) is the major reason for the high mortality rates among men worldwide. In fact, current therapeutic approaches are not successful. It appears that discovering more effective methods considering several parameters such as availability, low cost, and no toxicity to normal cells is one of the biggest challenges for interested researchers. Green tea (extracted from the plant Camellia sinensis) with high level of polyphenolic compounds and as the most globally consumed beverage has attracted considerable interest. MicroRNAs (or miRNAs) were considered as novel tools in cancer therapy which modulate various biological events in cell by regulation of gene expression. The aim of the current study was to evaluate the antitumor activity of green tea in LNCaP cells through up-regulation of miR-181a expression.

 First, LNCaP cells were cultured and by using quantitative real time PCR (qRT-PCR) and western blot methods, the expression levels of Bax and BCL2 were analyzed. Next, a 3D cell culture model was applied to evaluate the expression of miRNA-181a in LNCaP cells.

 It was shown that green tea induced cellular apoptosis. The high number of apoptotic nuclei was also shown by using DAPI staining. The inhibition of tumor growth was revealed by analyzing the size and number of spheroids. Also, up-regulation of miR-181a expression in LNCaP cells was revealed after treatment with green tea.

 Our results are helpful to design antitumor regimens based on consumption of green tea through up-regulation of miRNA-181a expression and induction of apoptosis.

Pseudomonas aeruginosa is an opportunistic nosocomial infection implicated in bacteremia in patients with compromised host defenses. Resistance to ciprofloxacin and imipenem, which are considered as suitable therapeutic options, is increasing in P. aeruginosa. Curcumin is a diferuloylmethane with antimicrobial properties. The present study was conducted to find the molecular effects of curcumin on clinical isolates with mutated genes involved in ciprofloxacin resistance. Fifty-two clinical isolates of P. aeruginosa were obtained from several hospitals and laboratories in Guilan province, northern Iran. Susceptibility to five antibiotics was evaluated by disc diffusion and broth dilution (MIC) methods. Furthermore, PCR-sequencing was carried out to evaluate mutations in topoisomerase subunits, five negative regulators of efflux pumps and oprD gene in these isolates. The effects of curcumin on the expression of mexB and mexY were evaluated using Q-RT-PCR.Of 52 P. aeruginosa isolated strains, 32-44% resistance to amikacin, ciprofloxacin, imipenem and gentamicin was observed. All isolates had mutation in gyrA. Some isolates had mutation in other topoisomerase subunits, some negative regulator genes and oprD gene. Curcumin (400µg/ml) along with ciprofloxacin (subMIC) increased ciprofloxacin susceptibility in four isolates. In these isolates, the expression of MexB and MexY efflux pump genes were downregulated. It seems that among P. aeruginosa isolates with various mutations in important genes in antibiotic resistant pathways, curcumin can intelligently sensitize isolates to these drugs.

The miRNAs are referred to small non-coding RNAs (consisting of 18 to 25 nucleotides). Functional studies have shown their functions to be oncogenes or tumor suppressor genes in different types of cancers. The miR-106b and miR-21 have been identified to participate in the biological behaviors of cells. This study aimed to evaluate the tissue and plasma levels of miR-21 and miR-106b in patients with breast cancer who were diagnosed with ductal carcinoma.

In total, 40 cases of breast cancer patients 180 samples were examined in this project. Samples included ductal carcinoma breast tumors (n=40), normal breast tissues of the margin of the tumor (n=40) and 20 samples from unaffected mammary tissue of females undergoing reduction mammoplasty (control group), plasma samples of patients with breast cancer (n=40), and plasma of non-affected individuals (n=40). The expression levels of miR-106b and miR-21 were determined using SYBR Green real-time RT-PCR assay in breast tissues and plasma of cancerous patients in comparison to the controls.

MiR-106b and miR-21 revealed much higher expression in tissues and plasma of patients with breast cancer in comparison to that in the group of control (P<0.001). High levels of mir-106b and miR-21 expression in plasma and tumor tissues were highly correlated with tumors in higher stages and lymph node involvement (P<0.0001).

Based on the obtained results, upregulation of miR-106b and miR-21 in the plasma of patients with breast cancer can act as a possible non-invasive biomarker for breast cancer prognosis. Further follow-up studies are required to confirm this.

Non-syndromic hearing loss is a genetically heterogeneous disorder. Mutation in GJB2 gene is a major cause of non-syndromic hearing loss in many countries. The aim of this study was to evaluate GJB2 mutations in 31 individuals with non-syndromic hearing loss in Guilan province.

In this descriptive cross-sectional study, blood samples were collected from 31 individuals with non-syndromic hearing loss in Rasht and Bandar Anzali cities. After DNA isolation, GJB2 gene was amplified by PCR method and underwent sequencing.

In this study, three mutations were determined in 18 individuals with hearing loss. 35delG mutation had the highest frequency (48.38%) in individuals with hearing loss as homozygote (in 14 individuals) and heterozygote (in 2 individuals). A patient with heterozygosity in V153I mutation and a patient with compound heterozygosity in 35delG/G200R mutation were determined. 

It appears that 35delG mutation is a common mutation in GJB2 gene in individuals with non-syndromic hearing loss in Guilan province

Gastric cancer is one of the five most common cancers in Iran, the sixth most common cancer in the world, and the second cause of cancer-related death worldwide. Failure to diagnose gastric cancer in early stages suggests the need to find potential biomarkers. This study aimed to evaluate the miR-195 expression as a potential biomarker in the plasma of gastric cancer patients in Guilan province.

In this case-control study, the Q-RT-PCR method was used to evaluate the expression level of miR-195 in the plasma of 25 patients with gastric cancer and 25 normal individuals. The relationship between the expression level of miR-195 and clinicopathologic features was evaluated using the ANOVA test. The receiver operating characteristic (ROC) and area under the curve (AUC) were used to evaluate the miR-195 as a potential biomarker to discriminate cancerous from non-cancerous states of the samples.

Our analysis showed that miR-195 was significantly downregulated in gastric cancer patients compared to the normal individuals (p˂0.05). The AUC value of ROC analysis was 0.7325±0.008 (p=0.0119) with the sensitivity of 51.7% and specificity of 71.8%.

Downregulation of miR-195 in gastric cancer patients and ROC analysis suggested that miR-195 can be introduced as a potential biomarker in the diagnosis of gastric cancer in Guilan province.

Gastric cancer (GC) is the most prevalent malignancy worldwide and a common cause of death in Iran. Studies have proved that a variety of dysregulated microRNAs is involved in the development and progression of gastric cancer. The present study aimed to evaluate the expression levels of plasma circulating oncogenic miR-21 and miR-192 and their association with clinical phenotypes of patients with gastric cancer in the north of Iran.

Clinico-pathological analysis was conducted using a standard protocol and pathological tests. The expression levels of miR-21 and miR-192 were measured using quantitative reverse transcription-polymerase chain reaction in the plasma of twenty pre/post-operative gastric cancer patients and twenty healthy subjects. The receiver operating characteristic (ROC) curve of these microRNAs was analyzed to investigate their diagnosis properties.

The study results indicated that plasma miR-21 expression was significantly associated with tumor stage and helicobacter pylori infection status (P=0.024, P=0.0004, respectively). However, no association was observed between clinic-pathological characteristics and miR-192 expression. The results showed that the plasma levels of miR-21 (P=0.0001) and miR-192 (P=0.0007) were significantly higher in GC patients compared to those in healthy individuals. Furthermore, the ROC analyses yielded the mean ±SD area under the curve (AUC) values of 0.9525±0.03 (P<0.0001) and 0.5925±0.09 (P=0.316) for miR-21 and miR-192, respectively. Pearson regression analysis showed that there was no significant correlation between the expression of miR-21 and miR-192 (P=0.1507).

Based on the obtained results, the expression of the plasma level of miR-21 was significantly higher in gastric cancer patients compared to that in the healthy group. Furthermore, the higher levels of AUC in miR-21 indicated the potential role of miR-21 as a noninvasive biomarker for the prognosis of gastric cancer in the population of the north of Iran.

Gastric cancer (GC) is a global health problem and the second deadly type of cancer worldwide with 1000 deaths per year. Poor prognosis in the early stages is one of the burdens in the treatment of GC. MicroRNAs are 18-22 nucleotide non-coding RNAs which play critical roles in the regulation of gene expression. Nowadays, miRNAs are widely known as non-invasive biomarkers for various kinds of cancers. This study aimed to evaluate the expression level of circulating miR-16 and miR-26a in GC patients and investigate the potential prognostic role of these miRNAs.

Initially, 20 plasma samples were obtained from pre-and post-operative GC patients, and the expression of miR-16 and -26a were compared with that of 20 healthy controls. The miRNAs expression was investigated using Real-Time quantitative PCR. The association between the expression levels of these miRNAs and clinicopathological features was also investigated in this study.

MiR-16 was down-regulated in GC patients; however, miR-26a expression revealed no significant difference between patients and controls in this regard. Furthermore, the expression of two miRNAs showed no association with the grade, TNM stage, and smoking status of the patients. Eventually, decreased expression of miR-16 was not correlated with the expression level of miR-26a.

The downregulation of circulating miR-16 introduces this microRNA as a candidate biomarker for the non-invasive early prognosis of GC.

Cancer stem cells (CSCs) have powerful self-renewal ability and tumor recurrence. Pancreatic ductal adenocarcinoma is a malignancy with high mortality rate and ˃5% survival. Silybin has anticancer and hepatoprotective properties. We loaded silybin in PEG400-OA (SPNs) and evaluated its cytotoxic effects on PANC-1 cells and PANC-1 CSCs.   Spheroids from PANC-1 cells were obtained by the hanging drop method. Anti-proliferative and apoptotic functions of SPNs were evaluated in spheroids and non-spheroids with MTT, DNA fragmentation, PI and PI/AnnexinV assays. The expression of CD markers was assessed with flow cytometry. QRT-PCR was used to evaluate the expression of some miRNAs and targets.    IC50 of SPNs was identified to be 50 µg/ml, 45 µg/ml, and 42µg/ml, respectively after 24 hr, 48 hr, and 72 hr in PANC-1 treated cells. PI staining and PI/AnnexinV assay showed that ~20%, ~60%, and ~80%, of cells treated with 30, 50, and 60 µg/ml of SPNs were in sub-G1 and apoptosis phase, respectively. DNA degradation was confirmed after SPNS stimulation. CD24, CD44, and CD133 expression decreased after SPNs treatment both in PANC-1 spheroid cells and PANC-1 cancer cell line. Under-expression of onco-miRs (miR-21, miR-155, and miR-221), over-expression of several apoptotic potential targets of oncomiRs (Bax, Casp-9, and P53), over-expression of tumor suppressive-miRs (let-7b, miR-34a, and miR-126), and under-expression of Bcl-2 was found in SPNs-treated cells.   We suggest that silybin encapsulated in polymersomes (SPNs) may be useful as a complementary agent for destroying both pancreatic cancer cells and pancreatic CSCs  along with chemotherapeutic agents.