Tim3 and PD-1 as a therapeutic and prognostic targets in colorectal cancer: Relationship with sidedness, clinicopathological parameters, and survival.

Background: Colorectal cancer (CRC) is a heterogeneous disease that complicates predicting patients' prognosis and their response to treatment. CRC prognosis is influenced by the tumor microenvironment (TME). The immune system is a critical component of the TME. Programmed cell death receptor 1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (Tim3) are inhibitory immune checkpoints that regulate immune response and may provide prognostic power. However, the effect of their expressions and co-expressions on the CRC prognosis remains unclear. Accordingly, this study aimed to investigate the prognostic value of the CD8, CD3, PD-1, Tim3 expression, and PD-1/Tim3 co-expression in patients with CRC. Materials and Methods: One hundred and thirty six patients with CRC who underwent curative surgery were enrolled in the study. Immunohistochemical staining was performed for PD-1, Tim3, CD8, and CD3, and the expression of each marker was evaluated in the center of the tumor (CT), invasive margin (IM), and adjacent normal-like tissue. Result: Our results indicated that high expression of PD-1 in IM was significantly associated with lower TNM stage, T-stage, M-stage, lack of metastasis, the presence of tertiary lymphoid structure (TLS), lack of recurrence (in the left-sided tumors), and larger tumor size (in right-sided tumors) (P<0.05). High expression of PD-1 in IM was also associated with improved overall survival (OS) in a subgroup of patients with high CD8 expression. High Tim3 expression in CT was associated with higher M-stage (M1) (in left-sided CRCs) (P<0.05). It was also associated with decreased OS in total cohort and left-sided CRCs and represented an independent prognostic factor for CRC patients in multivariate analysis. PD-1 and Tim3 co-expression had no synergistic effects on predicting OS. Conclusion: Our findings suggest that the clinicopathological and prognostic significance of immune system-related markers such as CD8, PD-1, and Tim3 depends on the primary tumor sides. We also showed that Tim3 could act as a prognostic factor and therapeutic target in CRC. This marker is probably a more preferred target for immunotherapy than PD-1, especially in left-sided CRCs.

Immunogenic cell death inducer peptides: A new approach for cancer therapy, current status and future perspectives.

Immunogenic Cell Death (ICD) is a type of cell death that kills tumor cells by stimulating the adaptive immune response against other tumor cells. ICD depends on the endoplasmic reticulum (ER) stress and the secretion of Damage-Associated Molecular Patterns (DAMP) by the dying tumor cell. DAMPs recruit innate immune cells such as Dendritic Cells (DC), triggering a cancer-specific immune response such as cytotoxic T lymphocytes (CTLs) to eliminate remaining cancer cells. ICD is accompanied by several hallmarks in dying cells, such as surface translocation of ER chaperones, calreticulin (CALR), and extracellular secretion of DAMPs such as high mobility group protein B1 (HMGB1) and adenosine triphosphate (ATP). Therapeutic peptides can kill bacteria and tumor cells thus affecting the immune system. They have high specificity and affinity for their targets, small size, appropriate cell membrane penetration, short half-life, and simple production processes. Peptides are interesting agents for immunomodulation since they may overcome the limitations of other therapeutics. Thus, the development of peptides affecting the TME and active antitumoral immunity has been actively pursued. On the other hand, several peptides have been recently identified to trigger ICD and anti-cancer responses. In the present review, we review previous studies on peptide-induced ICD, their mechanism, their targets, and markers. They include anti-microbial peptides (AMPs), cationic or mitochondrial targeting, checkpoint inhibitors, antiapoptotic inhibitors, and "don't eat me" inhibitor peptides. Also, peptides will be investigated potentially inducing ICD that is divided into ER stressors, ATPase inhibitors, and anti-microbial peptides.

Clinicopathological significance and prognostic role of LAG3 + tumor-infiltrating lymphocytes in colorectal cancer; relationship with sidedness.

BACKGROUND: It is well-documented that the interplay between tumor-infiltrating lymphocytes (TILs) and tumor cells is a major determining factor in cancer progression. CD45RO seems to be a reliable indicator for predicting prognosis and disease outcome, along with CD3 and CD8 markers. LAG-3 is another important marker that overexpresses on TILs in a variety of cancers and is associated with disease prognosis; however, its prognostic impact is controversial. Hence, in the present study, we aimed to investigate the presence of CD45RO + , LAG3 + , CD3 + , and CD8 + lymphocytes in CRC tumor tissues and their association with clinicopathological parameters of the disease as well as patients' survival, according to primary tumor locations. METHODS: Expression of CD45RO, LAG3, CD3, and CD8 was immunohistochemically assessed in tissue sections of 136 patients with CRC. The percentages of TILs expressing these markers were then separately determined in both invasive margin (IM) and center of tumor (CT). Their associations with clinicopathological factors and patients' survival were analyzed in the entire cohort and the subgroups of patients with right- and left- rectum tumors. RESULTS: Based on our observation, CD45RO + and CD3 + cells were the most frequent infiltrated lymphocytes in both CT and IM regions of colon tumor tissue. Whilst, LAG3 + lymphocytes were the least frequent subset in both areas. Statistical analysis indicated that the frequency of CD45RO + TILs was positively associated with advanced TNM stages (III/IV), in the entire cohort and right-sided tumors (P < 0.05). LAG3 + TILs in IM were also increased in tumor tissues with higher T-stages in the entire cohort (P = 0.027). In univariate analysis, high score of CD45RO + TILs in IM was associated with better overall survival in the entire cohort. High score of CD8 + and CD45RO + lymphocytes in IM were also associated with improved survival in patients with right-sided tumors. CONCLUSIONS: Our findings generally suggest that the clinicopathological and prognostic significance of immune system-related markers such as CD45RO and LAG3 depends on the primary tumor sides. Our results collectively demonstrated that infiltration of CD45RO + lymphocytes in IM could be an independent prognostic factor in a site-dependent manner.

The role of unfolded protein response-associated miRNAs in immunogenic cell death amplification: A literature review and bioinformatics analysis.

Immunogenic cell death (ICD) is a type of cellular death that is elicited in response to the specific types of anti-cancer therapies and enhances the anti-tumor immune responses by the combination of antigenicity and adjuvanticity of dying tumor cells. There is a well-established interlink between endoplasmic reticulum stress (ERS) and ICD elicited by anti-cancer therapies. Most recent evidences support that unfolded protein response (UPR)-associated miRNAs can be key players in the ERS-induced ICD. Hence, in the present study, we conducted a literature review on the role of these miRNAs and associated molecular pathways that may regulate ICD. We first collected UPR-associated miRNAs that promote ERS-induced apoptosis and then focused on microRNAs (miRNAs) that promote ERS-induced apoptosis via PERK/eIF2α/ATF4/CHOP pathway activation, as the main core for ICD and release of damage-associated molecular patterns. To better identify PERK/eIF2α/ATF4/CHOP pathway-inducing miRNAs that can be used as potential therapeutic targets for improving ICD in cancer treatment, we did a comprehensive bioinformatics analysis and network construction. Our results showed that "pathways in cancer", "MAPK signaling pathway", "PI3K-Akt signaling pathway", and "Cellular senescence", which correlate with UPR components and ERS induction, were among the significant signaling pathways related to the target genes of these miRNAs. Furthermore, a protein-protein interaction (PPI) network was constructed, which revealed the involvement of the PPI-extracted hub genes in the regulation of proliferation and apoptosis. In conclusion, we propose that these types of miRNAs can be considered as the potential cancer therapy options for better induction of ICD in combination with other ICD inducers.

Expression Analysis of Five Different Long Non-Coding Ribonucleic Acids in Nonsmall-Cell Lung Carcinoma Tumor and Tumor-Derived Exosomes.

Long non-coding ribonucleic acids (LncRNAs) are recently known for their role in regulating gene expression and the development of cancer. Controversial results indicate a correlation between the tissue expression of LncRNA and LncRNA content of extracellular vesicles. The present study aimed to evaluate the expression of different LncRNAs in non-small cell lung cancer (NSCLC) patients in tumor tissue, adjacent non-cancerous tissue (ANCT), and exosome-mediated lncRNA. Tumor and ANCT, as well as serum samples of 168 patient with NSCLC, were collected. The GHSROS, HNF1A-AS1, HOTAIR, HMlincRNA717, and LINCRNA-p21 relative expressions in tumor tissue, ANCT, and serum exosomes were evaluated in NSCLC patients. Among 168 NSCLC samples, the expressions of GHSROS (REx = 3.64, p = 0.028), HNF1A-AS1 (REx = 2.97, p = 0.041), and HOTAIR (REx = 2.9, p = 0.0389) were upregulated, and the expressions of HMlincRNA717 (REx = −4.56, p = 0.0012) and LINCRNA-p21 (REx = −5.14, p = 0.00334) were downregulated in tumor tissue in contrast to ANCT. Moreover, similar statistical differences were seen in the exosome-derived RNA of tumor tissues in contrast to ANCT samples. A panel of the five lncRNAs demonstrated that the area under the curve (AUC) for exosome and tumor was 0.937 (standard error: 0.012, p value < 0.0001). LncRNAs GHSROS, HNF1A-AS1, and HOTAIR showed high expression in tumor tissue and exosome content in NSCLC, and a panel that consisted of all five lncRNAs improved diagnosis of NSCLC.

Immune checkpoint inhibitors as mediators for immunosuppression by cancer-associated fibroblasts: A comprehensive review.

The tumor microenvironment (TME) is a significant contributor to cancer progression containing complex connections between cellular and chemical components and provides a suitable substrate for tumor growth and development. Growing evidence shows targeting tumor cells while ignoring the surrounding TME is not effective enough to overcome the cancer disease. Fibroblasts are essential sentinels of the stroma that due to certain conditions in TME, such as oxidative stress and local hypoxia, become activated, and play the prominent role in the physical support of tumor cells and the enhancement of tumorigenesis. Activated fibroblasts in TME, defined as cancer-associated fibroblasts (CAFs), play a crucial role in regulating the biological behavior of tumors, such as tumor metastasis and drug resistance. CAFs are highly heterogeneous populations that have different origins and, in addition to their role in supporting stromal cells, have multiple immunosuppressive functions via a membrane and secretory patterns. The secretion of different cytokines/chemokines, interactions that mediate the recruitment of regulatory immune cells and the reprogramming of an immunosuppressive function in immature myeloid cells are just a few examples of how CAFs contribute to the immune escape of tumors through various direct and indirect mechanisms on specific immune cell populations. Moreover, CAFs directly abolish the role of cytotoxic lymphocytes. The activation and overexpression of inhibitory immune checkpoints (iICPs) or their ligands in TME compartments are one of the main regulatory mechanisms that inactivate tumor-infiltrating lymphocytes in cancer lesions. CAFs are also essential players in the induction or expression of iICPs and the suppression of immune response in TME. Based on available studies, CAF subsets could modulate immune cell function in TME through iICPs in two ways; direct expression of iICPs by activated CAFs and indirect induction by production soluble and then upregulation of iICPs in TME. With a focus on CAFs' direct and indirect roles in the induction of iICPs in TME as well as their use in immunotherapy and diagnostics, we present the evolving understanding of the immunosuppressive mechanism of CAFs in TME in this review. Understanding the complete picture of CAFs will help develop new strategies to improve precision cancer therapy.

Purinergic receptors are a key bottleneck in tumor metabolic reprogramming: The prime suspect in cancer therapeutic resistance.

ATP and other nucleoside phosphates have specific receptors named purinergic receptors. Purinergic receptors and ectonucleotidases regulate various signaling pathways that play a role in physiological and pathological processes. Extracellular ATP in the tumor microenvironment (TME) has a higher level than in normal tissues and plays a role in cancer cell growth, survival, angiogenesis, metastasis, and drug resistance. In this review, we investigated the role of purinergic receptors in the development of resistance to therapy through changes in tumor cell metabolism. When a cell transforms to neoplasia, its metabolic processes change. The metabolic reprogramming modified metabolic feature of the TME, that can cause impeding immune surveillance and promote cancer growth. The purinergic receptors contribute to therapy resistance by modifying cancer cells' glucose, lipid, and amino acid metabolism. Limiting the energy supply of cancer cells is one approach to overcoming resistance. Glycolysis inhibitors which reduce intracellular ATP levels may make cancer cells more susceptible to anti-cancer therapies. The loss of the P2X7R through glucose intolerance and decreased fatty acid metabolism reduces therapeutic resistance. Potential metabolic blockers that can be employed in combination with other therapies will aid in the discovery of new anti-cancer immunotherapy to overcome therapy resistance. Therefore, therapeutic interventions that are considered to inhibit cancer cell metabolism and purinergic receptors simultaneously can potentially reduce resistance to treatment.

Isolation of a lytic bacteriophage against extensively drug-resistant Acinetobacter baumannii infections and its dramatic effect in rat model of burn infection.

OBJECTIVES: Acinetobacter Baumannii is an opportunistic nosocomial pathogen belonging to the Moraxellaceae family. The emergence of multidrug resistant strains of this pathogen caused many problems for hospitals and patients. The aim of the current study was to isolate, identify, and morphologically, physiologically, and in vivo analyze a new lytic bacteriophage targeting extensively drug-resistant (XDR) A. baumannii. MATERIALS AND METHODS: Different wastewater samples were tested for isolation of lytic bacteriophage against 19 A. baumannii isolates obtained from patients hospitalized in a hospital in Arak, Iran, from January 2019 to March 2019. The phenotypic and genotypic characteristics of A. baumannii strains (resistance genes including: adeA, adeB, adeC, adeR, adeS, ISAba1, blaOXA-23, blaOXA-24) were analyzed. The isolated phage characteristics including adsorption time, pH and thermal stability, host range, one-step growth rate, electron microscopy examination, and therapeutic efficacy of the phage were also investigated. Therapeutic efficacy of the phage was evaluated in a rat model with burn infection of XDR A. baumannii. The lesion image was taken on different days after burning and infection induction and was compared with phage untreated lesions. RESULTS: The results showed unique characteristics of the isolated phage (vB-AbauM-Arak1) including high specificity for Acinetobacter baumannii, stability at a relatively wide range of temperatures and pH values, short adsorption time, short latent period, and large burst size. In relation to the therapeutic efficacy of the phage, the lesion area decreased in phage-treated groups over 14 days than in those untreated, significantly (p < 0.05). CONCLUSION: Our findings demonstrated that isolated lytic phage was able to eliminate burn infections caused by XDR A. baumannii in a rat model. So, it may be recommended as alternative options toward to developing a treatment for extensively drug resistant Acinetobacter infections.

Spontaneous Regression of Diffuse Large B-cell Lymphoma in a Patient with Ataxia-Telangiectasia.

Ataxia-telangiectasia (AT) is a type of primary immunodeficiency characterized by an autosomal recessive mode of inheritance and usually presents with progressive cerebellar ataxia in early life. This complex disease is associated with humoral and cellular immune dysfunction and other features including characteristic oculocutaneous telangiectasia and increased predisposition to cancers, particularly lymphoma and leukemia. An 11-year-old Iranian girl presented with primary immunodeficiency and was diagnosed as having AT according to her clinical manifestations and molecular findings. She had a history of two types of non-Hodgkin's lymphoma and showed spontaneous regression of her diffuse large B-cell lymphoma without any specific treatment. Gene mutations and dysfunction in patients with AT result in different manifestations including abnormal development of the thymus, immunodeficiency, increased susceptibility to malignancies, and increased radiosensitivity. No standard treatment is available for these patients. The use of immunotherapeutic strategies in patients with primary immune deficiency disease-associated tumors is potentially important.

Design and production of a novel chimeric human growth hormone superagonist fused to human Fc domain.

Background and purpose: Growth hormone (GH) has been known as a crucial metabolic hormone expressed at the pituitary and the other number of cells and tissues and responsible for body growth. Because of the short half-life of GH, daily subcutaneous injections were shown to be more effective for GH therapy. This represents a burden for patients. So, there is a strong effort from the industry to create a long-acting form of GH and lots of technologies like GH fusion proteins are used to increase GH half-life. Experimental approach: In this study, the Fc domain of human IgG1 with serine-glycine linkers was attached to the C-terminal of a GH superagonist via molecular cloning. The presence of recombinant vector in E. coli host was confirmed by PCR. SDS-PAGE and western blot analysis showed the expression of recombinant proteins in the bacterial lysate. The binding ability to growth hormone receptors is determined by ELISA. Findings / Results: Our results showed that the novel SupGH-Fc has a good binding affinity to its receptor in ELISA in comparison to standard GH, although it has a big size. Conclusion and implications: Our data in this study clearly demonstrated the expression of the SupGH-Fc in a recombinant protein expression system. It is an introduction to the production of the new recombinant GH, which can bind to its receptor more effectively than commercial growth hormones and also might have a longer half-life.

New Generation Vaccines for COVID-19 Based on Peptide, Viral Vector, Artificial Antigen Presenting Cell, DNA or mRNA.

At present, effective vaccines have been developed as the most successful approaches for preventing widespread infectious disease. The global efforts are focusing with the aim of eliminating and overcoming the Coronavirus Disease 2019 (COVID-19) and are developing vaccines from the date it was announced as a pandemic disease. In this study, PubMed, Embase, Cochrane Library, Clinicaltrial.gov, WHO reports, Science Direct, Scopus, Google Scholar, and Springer databases were searched for finding the relevant studies about the COVID-19 vaccines. This article provides an overview of multiple vaccines that have been manufactured from December 2020 up to April 2021 and also offers a perspective on their efficacy, safety, advantages, and limitations. Currently, there are several categories of COVID-19 vaccines based on Protein Subunit (PS), Inactivated Virus (IV), Virus Like Particle (VLP), Live Attenuated Virus (LAV), Viral Vector (replicating) (VVr) and Viral Vector (non-replicating) (VVnr) in progress or finalized as indicated by the WHO reporting of April 1, 2020.

Cellulose-Based Nanofibril Composite Materials as a New Approach to Fight Bacterial Infections.

Antibiotic resistant microorganisms have become an enormous global challenge, and are predicted to cause hundreds of millions of deaths. Therefore, the search for novel/alternative antimicrobial agents is a grand global challenge. Cellulose is an abundant biopolymer with the advantages of low cost, biodegradability, and biocompatibility. With the recent growth of nanotechnology and nanomedicine, numerous researchers have investigated nanofibril cellulose to try to develop an anti-bacterial biomaterial. However, nanofibril cellulose has no inherent antibacterial activity, and therefore cannot be used on its own. To empower cellulose with anti-bacterial properties, new efficient nanomaterials have been designed based on cellulose-based nanofibrils as potential wound dressings, food packaging, and for other antibacterial applications. In this review we summarize reports concerning the therapeutic potential of cellulose-based nanofibrils against various bacterial infections.

Diversity of HLA class I and class II alleles in Iran populations: Systematic review and Meta-Analaysis.

The human leukocyte antigen (HLA) system plays an essential role in the peptides antigen presentation and more regulation of immune responses. Regarding all HLA molecules' associations with various diseases and their clinical utilities in understanding drug reactions or prediction of transplantation outcome, there is a need for much more extensive HLA data generated from Asian countries. METHOD: A comprehensive search was conducted in electronic databases between 1990 and 2021 to identify relevant articles to HLA frequency in the normal Iranian population. Two independent reviewers screened and selected the eligible studies. After data extraction, the meta-analysis was performed using STATA version 14. The overall frequencies and their 95% confidence intervals (CIs) were obtained using the random-effects model. RESULTS: Among 1141 studies 78 were eligible for this study and the sample sizes varied from 14 to 15,600. The most frequent alleles of HLA class I were HLA-A*02 (22%; 95%CI: 20-24%; I2 = 88.63%), -B*35 (18%; 95%CI: 16-21%; I2 = 90.95%), -C*12 (18%; 95%CI: 13-22%; I2 = 89.51%). HLA-DQA1*01 (42%; 95%CI: 40-44%; I2 = 56.80%), -DQB1*03 (38%; 95%CI: 35-42%; I2 = 92.38%), and -DRB1*11 (24%; 95%CI: 22-26%; I2 = 90.72%) were the most frequent alleles of HLA class II in Iran. DISCUSSION: Our meta-analysis results point out that the comprehensive report of HLA allele frequency in the Iranian population could be helpful as reference data for planning and managing transplantation and immune disease treatment in Iran.

Lactococcus-based vaccine against brucellosis: IgG immune response in mice with rOmp16-IL2 fusion protein.

This study was designed to introduce the recombinant Lactococcus lactis MG1363 as a cell factory candidate for production of recombinant Brucella melitensis Omp16-Human IL2 (r-Omp16-IL2) and to suggest it as a promising safe, non-pathogenic mucosal live vaccine against brucellosis. Three groups of BALB/c mice (10 mice per group) were intragastrically administrated with phosphate-buffered saline (PBS), L. lactis harboring the empty pAMJ2008 plasmid and with L. lactis expressing rOmp-IL2. The first two groups were classified as control groups and the third one is indicated as treatment group. Another group was injected by the intraperitoneal (i.p.) route with purified rOmp16-IL2 protein. The total serum IgG of each group was assessed with indirect ELISAs at two days before immunization and also two weeks after the last immunization. Results showed that BALB/c mice intragastrically administrated with L. lactis expressing rOmp-IL2 had dominant IgG response compared to the control (PBS administrated) group (P < 0.05). The level of IgG was significantly increased by intraperitoneally injection of recombinant Omp-IL2 in adjuvant compared to the intragastrically administration of PBS and L. lactis/pAMJ2008 as control groups, and also compared to L. lactis/pAMJ2008-rOmp-IL2 (P < 0.05). Our findings provide the use of L. lactis rOmp16-IL2 as a new promising alternative safe strategy than presently live attenuated vaccines toward developing an oral vaccine or subunit-based vaccine against brucellosis.

The association between HPV gene expression, inflammatory agents and cellular genes involved in EMT in lung cancer tissue.

BACKGROUND: Lung cancer is a leading cause of cancer morbidity and mortality worldwide. Several studies have suggested that Human papillomavirus (HPV) infection is an important risk factor in the development of lung cancer. In this study, we aim to address the role of HPV in the development of lung cancer mechanistically by examining the induction of inflammation and epithelial-mesenchymal transition (EMT) by this virus. METHODS: In this case-control study, tissue samples were collected from 102 cases with lung cancer and 48 controls. We examined the presence of HPV DNA and also the viral genotype in positive samples. We also examined the expression of viral genes (E2, E6 and E7), anti-carcinogenic genes (p53, retinoblastoma (RB)), and inflammatory cytokines in HPV positive cases. RESULTS: HPV DNA was detected in 52.9% (54/102) of the case samples and in 25% (12/48) of controls. A significant association was observed between a HPV positive status and lung cancer (OR = 3.37, 95% C.I = 1.58-7.22, P = 0.001). The most prevalent virus genotype in the patients was type 16 (38.8%). The expression of p53 and RB were decreased while and inflammatory cytokines were increased in HPV-positive lung cancer and HPV-positive control tissues compared to HPV-negative lung cancer and HPV-negative control tissues. Also, the expression level of E-cad and PTPN-13 genes were decreased in HPV- positive samples while the expression level of SLUG, TWIST and N-cad was increased in HPV-positive samples compared to negative samples. CONCLUSION: Our study suggests that HPV infection drives the induction of inflammation and EMT which may promote in the development of lung cancer.

Production of Brucella melitensis Omp16 protein fused to the human interleukin 2 in Lactococcus lactis MG1363 toward developing a Lactococcus-based vaccine against brucellosis.

The use of the food-grade bacterium Lactococcus lactis as a new cell factory is a promising alternative expression system for producing a desired protein. The Omp16-IL2 fusion protein antigen was cloned, expressed, and purified in this study. The Omp16-IL2 fusion gene was designed and cloned in pGH plasmid with appropriate restriction sites and subcloned in pAMJ2008 expression vector digested with the same enzymes. The purified recombinant constructed pAMJ-rOmp-IL2 was introduced into L. lactis subsp. cremoris MG1363 by electrotransformation. Finally, the expression and purification of Omp16-IL2 fusion protein was investigated. This study reports the construction of a recombinant L. lactis expressing the Omp16-IL2 fusion protein as an oral Lactococcus-based vaccine, as compared with commonly used live attenuated vaccines, for future studies against brucellosis.

Organochlorine pesticides contamination in agricultural soils of southern Iran.

There is limited information about pesticide contamination in Iran's agricultural land, particularly in plains producing exportable fruits. The aim of this investigation was to evaluate the concentration of organochlorine pesticides (OCPs) including hexachlorocyclohexane (HCH), heptachlor, dichloro-diphenyl-trichloroethane (DDT), chlordane (CHL), and their isomers compounds in agricultural soils of southern Iran. A total of 28 topsoil samples were collected from agricultural lands of Dalaki and Shabankare areas, Bushehr, Iran. In Dalaki area, the mean value of ΣHCH (α, ß, γ, δ), ΣDDT (o,p-DDE, o,p-DDD, o,p-DDT, p,p-DDE, p,p-DDD, p,p-DDT, and DDT), and ΣCHL (Trans-chlordane, Cis-chlordane, Heptachlor-exo-epoxide, and Heptachlor) was found to be 0.411 ng/g (dry weight, dw), 4.37 ng/g dw, and 2.04 ng/g dw, respectively. In Shabankare area the mean value of ΣHCH, ΣDDT, and ΣCHL was measured to be 1.38 ng/g dw, 11.99 ng/g dw, and 1.62 ng/g dw, respectively. The concentration trend of pesticides in both areas was as follows: DDT > CHL > HCH. Source identification indicated recent usage of HCH and DDT in the studied areas. Obtaining a cis-chlordane/trans-chlordane ratio greater than one in Shabankare farmlands showed that chlordane was not used recently. The health risk assessment showed that children and adults groups in both areas are exposed to negligible cancer risk. More serious attempts are necessary to reduce usage of OCPs during the agricultural process and the protection of soil and human health in the studied areas.

Effect of intramuscular hyoscine-n-butyl bromide on fallopian tube spasm and pain perception during and after hysterosalpingography in infertile women: A randomized single-blind controlled clinical trial.

Background: Hysterosalpingography plays an important role in diagnostic work-up and treatment planning for infertile women. This procedure is usually uncomfortable and painful. The present study plans to investigate the effect of intramuscular Hyoscine-N-Butyl Bromide (HBB) on fallopian tube spasm and pain perception during and after hysterosalpingography (HSG) in infertile women. Methods: This randomized single-blind controlled clinical trial (IRCT2017021132455N2) was conducted on infertile women scheduled for HSG in one radiology clinic affiliated to Arak University of Medical Sciences between July and August 2017. Patients were selected by convenience sampling and were randomly assigned to HBB (n=50) and a control group (n=50). Women received 20 mg/1cc HBB intramuscularly in the intervention group, 30 minutes before the procedure. Women in the control group did not receive any medication. The patients were requested to complete the Numeric Pain Rating Scale after injection of the dye, and also 30 minutes following the end of the HSG. Presence or absence of tubal spasm was determined after checking the radiographic images. For the data analysis using SPSS version 18, descriptive statistics, and analytical tests such as independent sample t-test, Mann- Whitney test, chi-square or Fisher's exact tests and logistic regression and ANCOVA were used. Results: Statistically significant differences were not observed in pain scores between the HBB and the control groups at the point of dye injection and 30 minutes after ending the HSG (p>0.05). Also, tubal spasm in the HBB group was lower than in the control group, but the differences were not statistically significant between the two groups (p=0.37). Conclusion: The use of intramuscular HBB before HSG has no advantage in reducing tubal spasm and the induced pain during dye injection and 30 minutes after the HSG procedure. Thus, we don't recommend HBB use before the HSG in order to relief from pain and spasm.

Metal(loid)s urinary level among workers of gas refinery and petrochemical companies: Health risk assessment of metal(loid)s in drinking water and dust.

BACKGROUND: Asalouyeh (southern Iran) contains many pollution sources like petrochemical and gas refinery companies. Few studies were conducted on the body burden of metal(loid)s in occupationally exposed workers of the companies in this area. OBJECTIVES: The urine concentration of metal(loid)s in workers of gas refinery and petrochemical companies in Asalouyeh (who have been worked as "two weeks work-two weeks rest" schedule) was evaluated during a before-and-after observational study. The risks of metal(loid)s in drinking water and dust particles in the studied area were also assessed. METHODS: Urinary samples (n = 179) were gathered at the first day of two weeks of work (before) and at the end of two weeks of work (after). The concentration of V, Ni, Mn, Cd, and As was measured using a graphite furnace atomic absorption spectrometry. The health hazards of metal(loid)s in the air dust and drinking water of workers were also evaluated. RESULTS: The median concentration of metal(loid)s for workers of gas refinery and petrochemical companies for before and after two weeks of work was measured, respectively, as: As (11.44 and 9.31 µg/L), Ni (1.06 and 0.51 µg/L), Cd (0.36 and 0.31 µg/L), Mn (0.29 and 0.24 µg/L), and V (0.08 and 0.05 µg/L). After two weeks work, the median of all metal(loid)s in the urine of petrochemical and gas refinery workers was significantly increased. The non-cancer risk due to intake metal(loid)s from drinking water was more than the threshold value and the cancer risk from drinking water and inhaled air dust was less than the threshold. CONCLUSION: Our results revealed the effect of gas refinery and petrochemical activities on increasing the metal(loid)s concentration of the worker's body and the necessity to protect this group. Additionally, the metal(loid)s intake from drinking water and inhaled dust posed no cancer risk to the workers.

Knockdown of Sal-like 4 expression by siRNA induces apoptosis in colorectal cancer.

Colorectal cancer (CRC) is known as the third most common malignancies among men and women and is also the second leading cause of cancer-related deaths worldwide. It has been indicated that a variety of risk factors are involved in the pathogenesis of CRC. Spalt-like transcription factor 4 (SALL4) is known as a transcription factor that plays an important role in the proliferation of cancerous cells. In this study, using a specific sequence of small interfering RNA (siRNA) against the sequence of SALL4, its activity is investigated in the CRC cell line (sw742). The CRC cells (sw742) were cultured and then, using a specific anti-SALL4 siRNA, their toxic doses were determined. Then, the gene is transfected into the cell. Proliferation and expression of the SALL4 and Bcl-2 gene were measured using the real-time polymerase chain reaction method. Cell death was evaluated by propidium iodide staining and fluorescence-activated cell sorting analysis. Our results indicated that the specific concentration of siRNA of the SALL4 gene was 62.5 nmole. Gene expression of SALL4 and Bcl-2 results showed that expression of Bcl-2 gene in the siRNA group was significantly reduced. In conclusion, our finding indicated that it could be used as a therapeutic and diagnostic biomarker in the treatment of patients with CRC.