Chronic treatment with TNF-α, alone and in combination with Takinib, SB203580 and metformin induce cell death in breast cancer.

Breast cancer (BC) is the most common malignancy, and the largest cause of cancer death among women. The interactions between tumor cells and tumor micro environmental factors have a major impact on tumor progression. One of the critical pro-inflammatory cytokines present in breast cancer tumor microenvironment is TNF-α. The aim of this study was to evaluate the long-term effect of TNF-α (1 week) along with p38 or TAK1 inhibitors as well as metformin on induction of cellular death, cancer stem cell and expression of metastatic marker CXCR4. MCF-7 and MDA-MB-231 cells were treated with TNF-α for one week and then were treated with combination of Takinib, SB203580 or Metformin; after all treatments were done, cell proliferation, cellular death, surface expression of CXCR4, CD44 and CD24 were determined. The results showed that treatment with TNF-α alone or in combination with Takinib, SB203580 and metformin elevated induction of cellular death in both cell lines compared to the control group. TNF-α also increased CXCR4 expression in MCF-7 cells, but it reduced its expression in the MDA-MB-231 cells. Also, breast cancer stem cells (BCSCs) population decreased in MDA-MB-231 cells treated with TNF-α alone or in combination with SB203580 and metformin. Although, in MCF-7 cells only combination of TNF-α and Takinib reduced BCSCs population in a time dependent manner. Altogether, we showed that TNF-α alone or in combination with other treatments can affect the progression of breast cancer.

The prevalence of colistin resistance in clinical Stenotrophomonas maltophilia isolates worldwide: a systematic review and meta-analysis.

While trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line therapy of Stenotrophomonas maltophilia infections, colistin is one of the therapeutic options in cases of allergy or resistance to TMP-SMX. However, understanding the global status of resistance to colistin amongst S. maltophilia isolates could be helpful for appropriate antibiotic prescription. This study aimed to conduct a systematic review and meta-analysis to examine the prevalence of colistin resistance in clinical S. maltophilia isolates worldwide. According to eligibility criteria, a total of 61 studies were included in the analysis. The pooled prevalence for colistin resistance was 42% (95% CI: 35-49%), ranging from 0.1 to 97%. Subgroups analysis indicated that, the pooled prevalence of colistin resistance was 44% (95% CI: 29-60%) in 15 studies during 2000-2010, and it was estimated to be 41% (95% CI: 33-50%) in 46 articles from 2011 to 2021. It was 46% (95% CI: 35-58%) in the studies that used broth microdilution method, and 39% (95% CI: 30-49%) in the studies with other used methods. The resistance rate in Asian countries was 45% (95% CI: 31-60%), in European countries was 45% (95% CI: 34-56%) and in the countries of North and South America was 33% (95% CI: 20-46%). Our review showed notable resistance to colistin in clinical S. maltophilia isolates. Given the estimated resistance rates, alternative antibiotics could be preferred to treat serious infections due to S. maltophilia.

A meta-analysis of the relationship between serums metrnl-like protein/subfatin and risk of type 2 diabetes mellitus and coronary artery disease.

There have been inconsistent reports that Metrnl-like protein, a new adipokine, is associated with the risk of metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD). A systematic search in PubMed, Scopus, Web of Science, and Google scholar databases were conducted up until 24 November 2020. Ten eligible studies were included in this meta-analysis. The overall results showed that there was no significant association between serum Metrnl levels and risk of T2DM and CAD in patients compared with healthy control (SMD= -0.717 and 95%CI -1.572_0.139, p = .1). However, in subgroup analysis, there was a significant association between a BMI ≥ 25 and the serum level of Metrnl-like protein (SMD= -0.688 and 95%CI -1.348_-0.028 p = .041), indicating a potential inverse connection between serum Metrnl and the adiposity. Further well-designed studies are needed to explain the more subtle roles of Metrnl in metabolic disorders like T2DM and CAD.

The potential association between metabolic syndrome and risk of post-surgical adhesion.

Metabolic syndrome (MetS) is defined by the clustering of several associated with a group of disorders that include: obesity, dyslipidemia, hypertension, and insulin resistance. The incidence of MetS is increasing globally around the world. Indeed the rates of different types of surgery in older or younger patients with Mets are increasing and they are exposed to a wide range of operations including abdominal, pelvic, urologic, or any invasive procedures. Post-surgical adhesion is a common problem and is a challenge for the surgeon. Despite many studies on its pathogenesis, there remain many un-answered questions about it, for example why certain tissues and patients are more at higher risk of post-surgical adhesions. Many studies have suggested that MetS is associated with up-regulating molecular mechanisms leading to chronic inflammation and hypercoagulability. In this review, we discuss some of the molecular mechanisms by MetS may enhance post-surgical adhesion, and particularly regarding those involved in coagulation and inflammation.

Relationship between mucosal TNF-α expression and Th1, Th17, Th22 and Treg responses in Helicobacter pylori infection.

Helicobacter pylori (H. pylori)-induced gastric inflammation in the gastric mucosa and significantly increases the risk of developing gastritis and peptic ulcer disease (PUD). The objective of this research is to determine the role of tumor necrosis factor-α (TNF-α) expression in the gastric mucosa of patients with H. pylori-associated gastritis and PUD compared to uninfected patients, and we determined the relation between TNF-α expression and Th1/Th17/Th22, and Treg cells. Fifty-five patients with H. pylori-associated gastritis, 47 patients with H. pylori-associated PUD, and 48 uninfected patients were in this research. Antrum biopsy was used to detect H. pylori, virulence factors and histopathological assessments. Expression of TNF-α in the infected group was significantly higher than the uninfected group. Also, cagA/oipA-positive infected patients induce significantly more TNF-α expression than do cagA/oipA-negative infected patients. Expression of TNF-α was significantly increased in the PUD group than the gastritis group. Notably, TNF-α expression had a significant positive correlation with the frequency of Th1/Th17/Th22 lymphocytes in the PUD group. These findings indicate the importance of increasing TNF-α with Th1, Th17, Th22 responses increase as an important risk factor for PUD in context of H. pylori infection.

The frequency of efflux pump genes expression in Acinetobacter baumannii isolates from pulmonary secretions.

Acinetobacter baumannii is an important opportunistic pathogen, and the cause of nosocomial infections worldwide in recent decades. Efflux pumps are considered as the important causes of multidrug resistance of A. baumannii. The aim of this study was to determine the frequency of efflux pump genes, and evaluate the antibiotic effect of Tigecycline on the expression of adeB gene in isolates of multidrug-resistant. A. baumannii. 70 isolates of A. baumannii were collected and confirmed by biochemical and molecular tests. Antibiotic resistance (Ciprofloxacin, Trimethoprim-sulfamethoxazole, and Tigecycline) was performed based on the minimum inhibitory concentration (MIC) method. Then, the effect of Carbonyl cyanide m-chlorophenyl hydrazone inhibitor (CCCP) on isolates was investigated and the frequency of adeB, adeG, adeJ and abeM genes were examined by PCR for isolates with reduced in MIC titer. Also, the antibiotic effect of Tigecycline on adeB gene expression in A. baumannii isolates was analyzed by Real-Time PCR. The antibiotic resistance for Ciprofloxacin, Trimethoprim-sulfamethoxazole, and Tigecycline was 97.1%, 95.8% and 37.2%, respectively. Following CCCP inhibitor use, the MIC titer had a decrease in MIC titer containing CCCP inhibitor was 64.3% for Ciprofloxacin, 51.5% for Trimethoprim-sulfamethoxazole and 50% for Tigecycline. The frequencies of genes associated with adeB, adeG, adeJ and abeM efflux pump were 100%, 92.8%, 86% and 98.5%, respectively. Real-Time PCR results showed a correlation between the antibiotic effects of Tigecycline on adeB gene expression. The antibiotic resistance of the isolates was relatively high. The isolates were resistant to Ciprofloxacin and Trimethoprim-sulfamethoxazole antibiotics, while more sensitive to Tigecycline. Also, efflux pump genes, which are the antibiotic resistance factors of A. baumannii, are frequently high in the isolates but it seems that isolates use other effluxe pumps than RND family to exit tigecycline.

The Potential Role of Changes in the Glucose and Lipid Metabolic Pathways in Gastrointestinal Cancer Progression: Strategy in Cancer Therapy.

BACKGROUND: Changes in cell metabolism are a well-known feature of some cancers, and this may be involved in the etiology of tumor formation and progression, as well as tumor heterogeneity. These changes may affect fatty acid metabolism and glycolysis and are required to provide the increase in energy necessary for the high rate of proliferation of cancer cells. Gastrointestinal cancers remain a difficult-to-treat cancer, particularly as they are usually diagnosed at a late stage of disease and are associated with poor outcomes. SUMMARY: Recently, the changes in the metabolic pathways, including the expression of the rate-limiting enzymes involved, have been considered to be a potential target for therapy for gastrointestinal tumors. KEY MESSAGE: A combination of routine chemotherapy drugs with metabolic inhibitors may improve the effectiveness of treatment.

Frequency of virulence-associated genotypes of Helicobacter pylori and their correlation with clinical outcome and histological parameters in infected patients.

Helicobacter pylori (H. pylori) is a gram-negative which can cause several gastroduodenal diseases, including gastritis and peptic ulcer disease (PUD). H. pylori specific genotypes have been related to increased occurrence of gastritis and PUD. The aim of this study was to investigate the clinical relevance of the major virulence factors of H. pylori with clinical outcomes and histological parameters in Iranian patients. Totally, 200 subjects with PUD and gastritis disease who underwent gastroduodenal endoscopy were enrolled in this study. The presence of the cagA, vacA, oipA, babA2, and iceA genes in antral gastric biopsy specimens were determined by polymerase chain reaction (PCR) and the results were compared with clinical outcomes and histological parameters. The frequency of babA2 + , oipA + , vacA s1/m2, and vacA m2 genes was significantly higher in patients with peptic ulcer disease compared with patients with gastritis. In contrast, the frequency of vacA s1/m1 gene was significantly higher in gastritis subjects than PUD subjects. The high-density scores of H. pylori were strongly associated with iceA1 ¯ , babA2 + , and oipA + genes. Additionally, the high polymorphonuclear cell infiltration and high mononuclear cell infiltration scores were strongly associated with the cagA + , iceA1 ¯ , oipA + genes and cagA + , babA2 + , oipA + genes, respectively. Our study indicated that the vacA, babA2, and oipA virulence factors are related to a higher risk of PUD in subjects with H. pylori-infection. Infection with these strains was associated with a more severe gastropathy.

High-level Gentamicin Resistance among Clinical Isolates of Enterococci in Iran: a Systematic Review and Meta-analysis.

Enterococci have been considered as one of the most common causes of nosocomial infections. The spread of antibiotic resistance has posed a serious challenge to treating the enterococcal infections. High-level aminoglycosides resistance leads to failure in the synergistic combination therapy. This study aimed to estimate the prevalence of high-level gentamicin resistance (HLGR) among clinical isolates of enterococci in Iran.Systematic literature search was conducted in the Web of Science, PubMed, Scopus and Google Scholar electronic databases from ar-ticles which were published from April 2000 to September 2018. Literature search yielded 918 studies. Eligible studies were selected ac-cording to the defined inclusion and exclusion criteria. Statistical heterogeneity was estimated by Q statistic and the I2 index. The Begg's rank correlation test and Egger's weighted regression tests were used to evaluate possible publication bias.Nineteen studies were included in this review. According to the meta-analysis results, the prevalence of HLGR among Enterococcus spp. was 49.4% (95% CI: 42.2%-56.6%). It was estimated 44.3% (95% CI: 38.1%-50.8%) and 66.3% (95% CI: 51.4%-78.6%) for E. faecalis and E. faecium, respectively.Since notable rate of HLGR in enterococci was seen in this analysis, improving the implementation of all aspects of the infection control programmes is required. Accurate and regular monitoring of infection control procedures are necessary for reducing the dissemination of such infections.

Phenotypic and genotypic detection of metallo-ß-lactamases in A. baumanii isolates obtained from clinical samples in Shahrekord, southwest Iran.

OBJECTIVE: Acinetobacter baumanii is a pathogenic bacterium that is the cause of many nosocomial infections. This study aimed to determine metallo-ß-lactamases (MBL) produced by the A. baumanii isolates obtained from clinical samples in Shahrekord, southwest Iran. RESULTS: A total of 100 A. baumanii were isolated from 250 clinical samples between June 2013 and June 2014. Then, the isolates were identified by biochemical tests, and MBL screening was conducted by the phenotypic tests modified Hodge, EDTA-disk synergy (EDS), combined disk (CD) and AmpC disc after antibiotic sensitivity test. Using PCR technique the bla genes were detected. Eighty-five (85%) isolates were resistant to meropenem and imipenem. Phenotypic tests showed that out of the 100 isolates, 46, 59, 50, 65 and 65 isolates were positive: AmpC disk, CD, EDS, Modified Hodge and E-test MBL respectively. Gene detection by PCR showed that 23 isolates carried the VIM-1 gene and only three isolates carried the IMP-1 gene. The prevalence of metallo-ß-lactamases isolates containing A. baumanii is increasing. Furthermore, the coexistence of various carbapenemases is dominantly act as a major problem. Continuous monitoring of the infections related to these bacteria should be considered to plan an alternative and new therapeutic strategies.

Agr typing of Staphylococcus aureus species isolated from clinical samples in training hospitals of Isfahan and Shahrekord.

OBJECTIVE: As an opportunistic pathogen, Staphylococcus aureus is associated with serious nosocomial infections and growing antimicrobial resistance against beta-lactams among S. aureus strains has become a global challenge. The current study was designed to investigate the presence of agr genes among S. aureus strains recovered from clinical samples in university hospitals of Isfahan and Shahrekord. RESULTS: A total of 150 S. aureus isolates were screened by Disk diffusion method (DDM) and conventional PCR. The minimum (17.3%) and maximum (46%) antibiotic resistance rates were found in vancomycin and cefoxitin, respectively. The majority of our isolates were classified as agr type I followed by type II, type IV, and type III. The statistical analysis showed a significant correlation between agr type I and antibiotic resistance against cefoxitin and erythromycin (p = 0.04 and p = 0.03, respectively). Based on our findings, the agr typing could be considered an effective approach for molecular tracking of S. aureus infections.

Prevalence and distribution of adhesins and the expression of fibronectin-binding protein (FnbA and FnbB) among Staphylococcus aureus isolates from Shahrekord Hospitals.

OBJECTIVE: One of the most important causes of nosocomial infections is Staphylococcus aureus. The aim of this study was to determine the frequency of these genes and the rate of expression of these genes during nasal colonization among the personnel of Kashani and Hajar hospitals. RESULTS: In this Analytical-descriptive study, 240 nasal swab specimens were collected from personnel of different departments of Kashani and Hajar hospitals in Shahr-e-kord. Nasal specimens were cultured and 110 Staphylococcus strains were isolated. Based on the results, 110 carriers of Staphylococcus aureus were identified. The frequency of clfA, clfB, fnbA and fnbB genes were 36.3%, 86.3%, 7.2% and 43.6% respectively. It was also observed that the fnbA gene showed no expression, but of 95 clfB-positive samples, 73 isolates (76.8%) were expressed clfB gene. This study showed that the abundance of these genes varies in nasal colonization. It was also observed that clfB gene with a high frequency and high expression rate has an important role in nose colonization. These results not only provide insight into the factors involved in S. aureus colonization but also provide potential therapeutic targets.

THE CHANGING TREND OF MORTALITY CAUSED BY GASTROINTESTINAL CANCERS IN IRAN DURING THE YEARS 2006-2010.

BACKGROUND: Cancers are one of the most important causes of death in the world. According to their high incidence and mortality, gastrointestinal cancers have particular importance among other cancers. OBJECTIVE: Therefore, this study was conducted to investigate the mortality change trends of gastrointestinal cancers in Iran. METHODS: This study was performed by analyzing the reported mortality data in 29 provinces of Iran in 2006-2010. Mortality trend of gastrointestinal cancers was drawn for both sexes in the study years and disaggregated by age groups and their frequency distribution. The WinPepi software was used for analysis. RESULTS: In the years 2006-2010, the mortality rate of, gastric, colorectal, liver and pancreatic cancers, has significantly increased. Totally, gastrointestinal mortality is higher in men than women. Also, the results showed that by increasing age, death from these cancers also increased. CONCLUSION: The most important causes of death from gastrointestinal cancers were gastric, liver and colorectal cancers in Iran and because of their increasing trend in the country, performing preventive interventions for the cancers' risk factors is necessary.

The highly conserved domain of RND multidrug efflux pumps in pathogenic Gram-negative bacteria.

RND (Resistance-Nodulation-Division) family transporters have a vital role in both intrinsic and acquired multi-drug resistance in Gram-negative bacteria. It is important to find a conserved domain in the RND family between different pathogenic bacteria for diagnostic and therapeutic purpose. Total sequences of three-component system RND efflux pumps were retrieved from NCBI nucleotide and protein database and were subjected to conservation and variation analysis using the multiple sequence alignment feature of the CLC workbench. The phylogenetic tree for main transporters was drawn and the three-dimensional structure was also evaluated. From the sequence conservation analysis, highly conserved residues with 282 base pair (94 amino acid) long were identified. The location of the highly conserved domain is positioned in the domain 1 crystallographic structure of AcrB Escherichia coli and MexB Pseudomonas aeruginosa. The main transporter component phylogenetic tree shows the clusters of different genotypes and their evolutionary association.  Each of three components of RND proteins is crucial for drug efflux, and the absence of even one component makes the entire complex totally nonfunctional. Therefore, this highly conserved region can be used to disable the RND multidrug efflux pumps. In addition, this highly conserved can also be used for diagnostic aspects.

A mudança da tendência de mortalidade causada por câncer gastrointestinal no Irã durante os anos 2006-2010 / The changing trend of mortality caused by gastrointestinal cancers in iran during the years 2006-2010

ABSTRACT BACKGROUND: Cancers are one of the most important causes of death in the world. According to their high incidence and mortality, gastrointestinal cancers have particular importance among other cancers. OBJECTIVE: Therefore, this study was conducted to investigate the mortality change trends of gastrointestinal cancers in Iran. METHODS: This study was performed by analyzing the reported mortality data in 29 provinces of Iran in 2006-2010. Mortality trend of gastrointestinal cancers was drawn for both sexes in the study years and disaggregated by age groups and their frequency distribution. The WinPepi software was used for analysis. RESULTS: In the years 2006-2010, the mortality rate of, gastric, colorectal, liver and pancreatic cancers, has significantly increased. Totally, gastrointestinal mortality is higher in men than women. Also, the results showed that by increasing age, death from these cancers also increased. CONCLUSION: The most important causes of death from gastrointestinal cancers were gastric, liver and colorectal cancers in Iran and because of their increasing trend in the country, performing preventive interventions for the cancers' risk factors is necessary.

RESUMO CONTEXTO: O câncer é uma das causas mais importantes de morte no mundo. De acordo com a sua alta incidência e mortalidade, o câncer gastrointestinal tem particular importância entre outros tipos de neoplasias. OBJETIVO: Este estudo foi conduzido para investigar as tendências de mudança de mortalidade de câncer gastrointestinal no Irã. MÉTODOS: Foi realizada pesquisa analisando-se os dados de mortalidade relatados em 29 províncias do Irã entre 2006-2010. A tendência de mortalidade de câncer gastrointestinal foi delineada para ambos os sexos nos anos de estudo e desagregadas por grupos etários em sua distribuição de frequência. O software WinPepi foi usado para análise. RESULTADOS: Nos anos 2006-2010, a taxa de mortalidade por câncer gástrico, colorretal, de fígado e pancreático aumentou significativamente. A mortalidade por câncer gastrointestinal é maior nos homens do que nas mulheres e, além disso, os resultados mostraram que com o aumentar a idade, a morte causada por estes cânceres também aumentou. CONCLUSÃO: As causas mais importantes da morte entre cânceres de origem gastrointestinal no Irã foram o gástrico, o hepático e o colorretal e devido a sua tendência crescente no país, a realização de intervenções preventivas para os fatores de risco é necessária.

Epidemiology of Panton-Valentine Leukocidin harbouring Staphylococcus aureus in cutaneous infections from Iran: a systematic review and meta-analysis.

Panton-Valentine Leukocidin (PVL) producing Staphylococcus aureus has been associated with severity of skin infections and pathology that suggest a major role in pathogenicity. The present study aimed to determine the overall prevalence of PVL harbouring S. aureus isolates from cutaneous infections in Iran. A systematic search was performed by using Medline electronic databases (PubMed) from the papers published by Iranian authors to the end of March 2017. Ten publications which met our inclusion criteria were then selected for data extraction and analysis by Comprehensive Meta-Analysis Software. The pooled prevalence of PVL in cutaneous infections was estimated at 27.9% (95% CI: 17.9-40.6). The range of PVL positivity among S. aureus isolates obtained from cutaneous infections was from 7.4% to 55.6%. In summary, despite the emergence of multiple-drug resistant strains, it seems that the overall prevalence of PVL carrying S. aureus in Iran remains steady regardless of methicillin resistance. However, further research is required to elucidate the interplay between the risk of invasive disease and PVL, especially in Iran.

Distribution and Diversity of hmw1A Among Invasive Nontypeable Haemophilus influenzae Isolates in Iran.

BACKGROUND: The pathogenesis of nontypeable Haemophilus influenzae (NTHi) begins with adhesion to the rhinopharyngeal mucosa. Almost 38-80% of NTHi clinical isolates produce proteins that belong to the High Molecular Weight (HMW) family of adhesins, which are believed to facilitate colonization. METHODS: In the present study, the prevalence of hmwA, which encodes the HMW adhesin, was determined for a collection of 32 NTHi isolates. Restriction Fragment Length Polymorphism (RFLP) was performed to advance our understanding of hmwA binding sequence diversity. RESULTS: The results demonstrated that hmwA was detected in 61% of NTHi isolates. According to RFLP, isolates were divided into three groups. CONCLUSION: Based on these observations, it is hypothesized that some strains of nontypeable Haemophilus influenzae infect some specific areas more than other parts.