drug resistance

Deactivation of drugs by enzymes, especially UDP-glucuronosyltransferases (UGT), is a reasons for resistance. The aim of this study was to investigate the interaction of UGT1A3, UGT1A1 and UGT2B7 enzymes with tyrosine kinase inhibitors. The structure of enzymes was made by homology modeling method and the structure of 300 tyrosine kinase inhibitors was obtained from Pubchem database. Molecular docking simulation was performed by PyRx 0.8 software and the complexes were sorted based on the most negative binding energy and zero RMSD and the amino acids involved in the binding were analyzed. In total, forty-five drugs were introduced as possible substrates of these three enzymes. The results showed that the binding site of these drugs were to the amino acids of the active site of the enzymes and the binding energy of the ligands to UGT1A1 was more negative than the other two enzymes. It can be suggested that the possible glucuronidation of these inhibitors by UGT enzymes can lead to two important events: first, their rapid removal from the blood circulation and creating drug resistance, and second, preventing bilirubin glucuronidation and increasing serum bilirubin level. Therefore, laboratory investigation of the relationship between these inhibitors and UGT enzymes can be necessary.

Staphylococcus aureus is a major human pathogen. This opportunistic pathogen is responsible for a variety of infections in humans. Biofilm formation is a key factor in infection development and drug resistance. Biofilm acts as a barrier and reduces bacterial exposure to antibacterial drugs. Targeting bacterial biofilm is a promising strategy to overcome drug resistance. In this work, the antibiofilm potential of ZnO-rutin nanoparticles was characterized. Growth inhibitory potential was studied using the broth microdilution method. Biofilm inhibitory effects of ZnO and ZnO-rutin nanoparticles were investigated by crystal staining and electron microscopy imaging was used to visualize the treated and untreated biofilms. The minimum inhibitory concentration (MIC) of the ZnO and ZnO-rutin nanoparticles for S. aureus strains was 0.5-1.0µg/mL. Treatment of S. aureus with ZnO and ZnO-rutin nanoparticles inhibited biofilm formation by 68.2 and 81.2%, respectively. In addition, exposure of S. aureus with ZnO-rutin nanoparticles considerably disrupted biofilm architecture, inhibited cell adhesion to the surface, and caused morphological alteration of biofilm architecture. Additionally, damage to cell surface was evident in the treated cells. This study shows that ZnO-rutin can be a promising candidate for combating biofilm-associated infection and drug resistance caused by S. aureus.

Urinary tract infections have significant complications and high costs and can lead to death. Appropriate treatment has been challenged due to high drug resistance. The aim of the present study was the biosynthesis of zinc oxide nanoparticles/banana peel on multi-drug resistant uropathogenic bacteria in children under two years of age.

In this study, bionanoparticles of zinc oxide/banana peel were synthesized and the structural, optical, morphological, and particle size characteristics were investigated using X-ray diffraction, ultraviolet absorption spectrum, and scanning electron microscopy. Biochemical tests and Colony-PCR technique were used to identify bacteria. The antibacterial properties of the synthesized nanoparticles were evaluated by the Agar dilution method on isolated bacteria.

According to the XRD, SEM, and UV-Vis results, the synthesized zinc oxide had a hexagonal structure with a size of 100 nm and absorption at a wavelength of 258 nm. Bacterial strains of Escherichia coli, Proteus mirabilis and Klebsiella pneumoniae multidrug-resistant Uropathogenic bacteria were identified using morphological, biochemical, and molecular characteristics. The results of antibacterial tests showed that bionanoparticles of zinc oxide/banana peel at a concentration of 0.6 g/L were effective against all bacteria.

The findings of this research showed that zinc oxide/banana peel bio-nanoparticles had an effective antibacterial effect against multi-drug resistant UTI bacteria in children under two years of age.

Resistance to chemotherapy drugs always has been an obstacle in the definitive treatment of cancers. Therefore, the discovery of molecular events leading to drug resistance improves therapeutic methods. Non-coding RNAs (ncRNAs) are a group of molecules that regulate intracellular events, including carcinogenesis and drug resistance pathways. For example, the competitive network of endogenous ncRNAs (ceRNA) regulates the mRNA expression of target genes by binding to miRNAs and limiting their regulatory effect. So far, limited studies have been reported on the role of ceRNA in drug resistance in ovarian cancer. In this study, large-scale RNAseq sequencing data obtained from cisplatin-resistant and sensitive cells were used to search for ceRNAs that are possible regulators of drug resistance in ovarian cancer. For this purpose, the A2780 sensitive and resistant cisplatin ovarian cancer cell line was selected, and the SRA data prepared by RNAseq method was screened. During this process, lncRNAs, microRNAs and mRNAs with expression changes were separated and classified. In the bioinformatic analysis of resistant and sensitive cells, 16 mRNAs, 10 lncRNAs, and 149 miRNAs were overexpressed, and 622 mRNAs, 263 lncRNAs, and 177 miRNAs were underexpressed. These genes were involved in 57 cellular pathways, and by mapping the regulatory ceRNA network, ZNRF3-AS1-miR-33-DUSP1 and ZNRF3-AS1-miR33-HSPA2 axes were identified as potential ceRNA networks involved in cisplatin-resistant ovarian cancer.

Urinary tract infections are one of the medical and health problems. This type of infection is more common in women than in men due to the anatomy of the urinary tract and lack of hygiene. The aim of the present study is to investigate the drug resistance of urinary pathogens in women with urinary tract infection in Savojbolagh city.

The current study is descriptive-cross-sectional, which was collected by examining 5100 urine samples from women suffering from and suspected of urinary tract infection, and after culturing in general-pourpose media and selective media and biochemical tests, the type of pathogenic microorganism was determined; then, the level of resistance in the strains was reported with antibiogram. Microsoft Excel 2022 software was used to draw graphs.

Out of a total of 5100 urine samples, 302 samples were considered positive, and the most infectious pathogens were Escherichia coli (%60.93) and group B streptococcus (%16.56). The age group of 31-40 years (%17.55) was recognized as the high-risk group, and the highest frequency of drug resistance in Escherichia coli to cefazolin (%60.87) and in group B streptococci to tetracycline (%88) was observed.

The amount of drug resistance of microorganisms is increasing day by day, and this issue is a threat to all humans and animals. In this study, the highest rate of drug resistance to cefazolin and tetracycline was observed in two pathogens, which are main causes of urinary tract infection.

Drug-resistant infection is one of the leading causes of death from burn injuries. Bacteriovorus stalpii, like other predators, invades and destroys the periplasmic space of gram-negative bacteria. The aim of the present study was to investigate the Bacteriovorus stalpii on the healing rate of Pseudomonas aeruginosa-infected burn wounds in rats.

30 albino rats were randomly divided into 5 groups of positive, negative, gentamicin, ciprofloxacin and staphylococcal bacteriorex after 3 burn wounds.30 rats N-MRI were randomly divided in to 5 groups positive and negative control, gentamicin, ciprofloxacin and Bacteriovorus stalpii, and except for the negative control group, all groups Burned and Infected by 4 multidrug resistant Pseudomonas isolates. After treatment with bacteria and antibiotics, wound colonies were reported every other day and wound area was measured within 20 days.

The results of colony count showed that Bacteriovorus stalpii in infected wounds significantly reduced the amount of bacteria in 21 days compared to other groups and this decrease was better than the performance of gentamicin and ciprofloxacin antibiotics. Measurement of wound area over 20 days also showed that the use of predatory bacteria reduced wound area in burnt rat compared to control groups. Histological examination of the resulting wounds showed that the predatory bacteria reduced inflammation, increased fibroblasts cell and increased tissue collagen compared to the control group.

Bacteriovorus stalpii can accelerate the treatment process in drug-resistant infections.

Climate change is one of the most important issues that has attracted a great deal of attention and caused many environmental problems for health systems and global economy. Studies have shown that during climate change, microorganisms can change and cause many problems including the recurrence and spread of infectious diseases, emerging diseases (COVID-19 pandemic), and antibiotic resistance. Besides, it will lead to famine, drought, floods, and global warming that threatens the lives of many people. Reducing greenhouse gas emissions, especially the use of less fossil fuels in industry, can be a preventative way. Therefore, it is significant to have plans to deal with climate change consequences in the environment. In this article, 71 articles from 1992 to 2020 were reviewed by mentioned keywords. Some specific extreme environments that are rich in valuable secondary metabolites and microorganisms but are fragile to climate change and also their microorganism’s diversity and population which have been changed during climate change were reviewed.

Streptomyces is the most important bacterial genus known to produce secondary antibiotic compounds. Considering the speed of bacterial resistance spread, it becomes more important to study less used compounds. Aminoglycosides disrupt the function of the target microorganism by acting on the protein-synthesis process. Paromomycin is an aminoglycoside that acts on a wide range of gram-positive, gram-negative bacteria and protozoa. Today, this antibiotic is mostly used in the treatment of visceral leishmaniasis. The main producer of paromomycin is S. rimosus NRRL 2455. Taking these antibiotics in high doses can cause widespread complications in the heart, kidneys, and auditory system, but in low doses and in combination with other types of antibiotics, it can significantly inhibit the growth of multidrug-resistant (MDR) bacteria. According to this information, it is important to know the factors that increase production and to understand the relationship between the structure and performance of this antibiotic. The aim of this study was to collect useful and up-to-date information about paromomycin, production conditions and the importance of this antibiotic in the treatment of bacterial MDR infections.

Many single nucleotide polymorphisms have been identified in the androgen receptor coding gene that play an important role in the development, prediction, and diagnosis of cancer. In this regard, this study was designed to evaluate the allelic frequency of rs137852579 single-nucleotide polymorphism in the androgen receptor coding gene in patients suffering from prostate cancer.

In this study, peripheral blood was taken in 10cc out of 50 prostate cancer patients and 50 healthy individuals. Genomic DNA of the samples was extracted and isolated. ARMS-PCR and direct sequencing were used to determine the presence of the desired polymorphism in population.

The results of this study showed that the allele frequency of rs137852579 for the C allele in the healthy group was 0.06 and in the patient group was 0.28. In addition, the heterozygosity rate showed that the Iranian population was in Hardy Weinberg equilibrium for this polymorphism (p> 0.05).

Based on the results of this study, it can be concluded that rs137852579 polymorphism in the androgen receptor gene can contribute to prostate cancer in the Iranian population.

Cancer stem cells are responsible for the formation the resistance to treatment, tumor relapse, and metastasis. miRNAs play an important role in the regulation of biological processes. Therefore, the purpose of this review is to candidate miRNAs that are involved in the regulation of all three properties including stemness, metastasis, and drug resistance and find their target genes and signaling pathways by using literature learning and data mining. The present systematic review is done to identify stemness-regulating miRNAs. By using CORMINE database, metastasis and drug resistance regulating miRNAs collected. Finally, we compared these three lists of miRNAs and found common miRNAs in these three properties. ONCO.IO database and KEGG pathway have been done to obtain the interaction between miRNA-miRNA target and cancer-related signaling pathway respectively. We collected 191 stemness-regulating miRNAs from 21 excluded studies. Based on CORMINE database, 161 miRNAs and 57 miRNAs had metastasis and stemness features respectively. We obtained 7 common miRNAs that 4 of them including has-miR-34a, has-miR-23a, has-miR-30a, has-miR-100 has a significant role for targeting signaling pathways involved in cancer and their most important targets regulate many processes of cells. These data suggest that three important properties can regulate by common miRNAs. Therefore, target these miRNAs or their targets can be helpful to stop tumor growth and metastasis and may be useful biomarkers for early detection of gastric cancer.

The aim of this study was to investigate the effect of rs141831067 Single nucleotide Polymorphism existence on therapeutic response of patients diagnosed with Prostate Cancer to Methotrexate and investigation of the polymorphism Frequency in Iranian population.

In this study, peripheral blood samples were taken from 50 healthy individuals and 50 patients suffering from prostate cancer. Then genomic DNA of each sample was extracted and isolated. ARMS-PCR and direct sequencing techniques were used to determine the presence of the polymorphism in populations. Finally, the statistical analysis of the results was performed by analyzing allelic frequency, heterozygosity, PIC analysis and Hardy Weinberg equilibrium analysis.

A comparative study of rs141831067 polymorphism existence showed that the allele frequency of this marker was significantly higher in the patients relative to healthy group (P-value = 0.002). In addition the bioinformatics analyzes of the interactions of the dihydrofolate reductase enzyme and methotrexate showed that existence of the polymorphism may alter the interaction patterns and result in the relative displacement of methotrexate position from the active site of dihydrofolate reductase.

Rs141831067 Single nucleotide Polymorphism in Dihydrofolate reductase gene plays an important role in the prostate cancer occurrence and this Single nucleotide Polymorphism can cause drug resistance to methotrexate in prostate cancer.