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1.
J Adv Med Educ Prof ; 12(1): 57-65, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38313418

RESUMEN

Introduction: Distance education as a training method is used today to train nurses around the world. This study aimed to determine the impact of using the community of inquiry model on the quality of distance learning of airway management among anesthesia nurse students. Methods: This is a quasi-experimental study with a pre-test post-test design conducted at Ahvaz Jundishapur University of Medical Sciences. Participants were selected by census, and they were second, third, and fourth-year nurse anesthesia students (n=66). The participants were assigned to intervention and control groups (n=33 each) based on the table of random numbers. Given the three dimensions of the community of inquiry model, interventions were carried out in terms of social, teaching, and cognitive dimensions to increase social presence, teaching presence, and cognitive presence. Data collection tools included a questionnaire. The data were analyzed using Independent T-test, paired T-test, ANCOVA, and Chi-square in SPSS software, version 16. Results: The results showed that the promotion of each of the three elements of the community of inquiry model had a significant effect on the quality of distance learning of airway management. Moreover, the mean scores of these elements were significantly different (P<0.001) in the intervention and control groups [teaching presence (3.742±0.453 vs. 2.573±0.241), social presence (2.245±0.488 vs. 1.434±0.297), and cognitive presence (3.421±0.569 vs. 2.369±0.223)]. Conclusion: The community of inquiry is a practical and effective framework for the better design and implementation of distance education courses. Therefore, nursing educators and course designers are strongly recommended to use this framework in nursing education.

2.
Avicenna J Med Biotechnol ; 15(2): 68-75, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37034891

RESUMEN

Background: Vimentin is a prominent Intermediate Filaments (IFs) protein expressed in different mesenchymal origin cell types. Besides a wide range of cellular function roles associated with vimentin expression, its dysregulation and cell surface expression in the induction of malignancy properties have been reported extensively, making it a promising cancer-specific target. Therefore, this study aimed to generate and characterize anti-vimentin monoclonal antibodies. Methods: A 14-mer synthetic peptide from vimentin was conjugated to Keyhole Limpet Hemocyanin (KLH) and used for immunization of Blab/C mice and monoclonal production by conventional hybridoma technology. The monoclonal antibody was purified using affinity chromatography of supernatants from the selected hybridoma cells. ELISA, Immunoprecipitation-Western blotting (IP-WB), Immunocytochemistry (ICC), and flow cytometry were employed to characterize the produced monoclonal antibody in terms of interaction with vimentin immunizing peptide as well as vimentin protein. Results: Amid the several obtained producing anti-vimentin antibody hybridomas, the 7C11-D9 clone (IgG1 isotype with kappa light chain) showed higher reactivity with the immunizing peptide, and led to its selection for purification and characterization. The purified antibody could detect vimentin protein in IP-WB, ICC and flow cytometry of the normal and cancerous cells with different origin. No vimentin expression was found in normal healthy Peripheral Blood Mononuclear Cell (PBMC). Conclusion: Taken together, 7C11-D9 anti-vimentin monoclonal antibody might be used as immune diagnostic or immune therapeutic tool where detection or targeting of vimentin in a wide range of organisms is required.

3.
J Bioinform Comput Biol ; 20(3): 2250015, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35880255

RESUMEN

Recepteur d'Origine Nantais known as RON is a member of the receptor tyrosine kinase (RTK) superfamily which has recently gained increasing attention as cancer target for therapeutic intervention. The aim of this work was to perform an alignment-independent three-dimensional quantitative structure-activity relationship (3D QSAR) study for a series of RON inhibitors. A 3D QSAR model based on GRid-INdependent Descriptors (GRIND) methodology was generated using a set of 19 compounds with RON inhibitory activities. The generated 3D QSAR model revealed the main structural features important in the potency of RON inhibitors. The results obtained from the presented study can be used in lead optimization projects for designing of novel compounds where inhibition of RON is needed.


Asunto(s)
Relación Estructura-Actividad Cuantitativa , Proteínas Tirosina Quinasas Receptoras , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Tirosina Quinasas Receptoras/metabolismo
4.
Iran J Pathol ; 17(2): 174-182, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35463727

RESUMEN

Background & Objective: Cell surface expression of sortilin in different types of cancer signifies it as a therapeutic target for cancer therapy. The aim of this study was to detect sortilin expression in bladder cancer cells using an anti-sortilin monoclonal antibody (mAb) to evaluate sortilin as a target for developing diagnostic and therapeutic agents against bladder carcinoma. Methods: The protein expression of sortilin in bladder cancer tissues and cell lines (5637 and EJ138) was investigated by immunohistochemistry (IHC), immune-cytochemistry (ICC), and flow cytometry. Furthermore, the capability of anti-sortilin mAb in apoptosis induction in bladder cancer cells was evaluated. Results: A high expression level was observed in bladder carcinoma tissues (P≤0.001) and cell lines, using IHC and ICC, respectively. Flow cytometry results showed cell surface expression of 27.5±3% (P≤0.01), 74.4±7.8% (P≤0.001), and 4.2±0.4% of sortilin in EJ138, 5637, and HFFF cells, respectively. In EJ138 anti-sortilin mAb induced apoptosis in 25.2±11.5% (P≤0.05) (early) and 4.5±1.1% (P>0.05) (late) after 6 h incubation, while for 12 h, the values of 11.6±3.8% (P>0.05) and 20.7±4.4% (P≤0.05) were achieved. In 5637 cells, 6 h incubation resulted in 10.2±0.3% (P>0.05) and 6.6±1.4% (P>0.05) apoptosis induction, while these values were 12.1±0.8% (P>0.05) and 27.4±4.5% (P≤0.01) after 12 h. The HFFF cells did not show significant apoptosis. Conclusion: The overexpression of sortilin in bladder tumor cells and its potential in inducing apoptosis via directed targeting with the specific monoclonal antibody may represent this protein as a potential candidate of targeted therapy in bladder carcinoma.

5.
Mol Inform ; 41(7): e2100231, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35068079

RESUMEN

BACKGROUND: Coronavirus disease 2019 (COVID-19) as global pandemic disease has been adversely affecting public health and social life with considerable loss of human life worldwide. Therefore, there is an urgent need for developing novel therapeutics to combat COVID-19. The causative agent of COVID-19 is SARS-CoV-2 which targets human angiotensin converting enzyme 2 (ACE2) as cellular receptor via its spike (S) protein. In this context, interfering with the binding of SARS-CoV-2 S protein to target molecules could provide a promising strategy to find novel therapeutic agents against SARS-CoV-2. The purpose of the current study was to identify potential peptidomimetics against S protein with a combination of structure-based virtual screening methods and in vitro assays. METHODS: The candidates were inspected in terms of ADME properties, drug-likeness, as well as toxicity profiles. Additionally, molecular docking and dynamics simulations were performed to predict binding of the studied ligands to spike protein. RESULTS: Biological evaluation of the compounds revealed that PM2 molecule exhibits some antiviral activity. CONCLUSION: In summary, this study highlights the importance of combining in silico and in vitro techniques in order to identify antiviral compound to tackle COVID-19 and presents a new scaffold that may be structurally optimized for improved antiviral activity.


Asunto(s)
Antivirales , Peptidomiméticos , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Antivirales/química , Simulación del Acoplamiento Molecular , Peptidomiméticos/farmacología , SARS-CoV-2/efectos de los fármacos , Glicoproteína de la Espiga del Coronavirus/antagonistas & inhibidores , Glicoproteína de la Espiga del Coronavirus/química
6.
Mol Inform ; 41(1): e2000181, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-33274845

RESUMEN

BACKGROUND: RON (Recepteur d'Origine Nantais) receptor tyrosine kinase is a promising target for anti-cancer therapeutics. The aim of this study was to identify new RON inhibitors using virtual screening methods. METHODS: To this end, a ligand-based virtual screening approach was employed for screening of ZINC database on the homology model of RON receptor. All the selected hits were inspected in terms of drug-likeness, ADME properties, and toxicity profiles. Ligand-based similarity searches along with further filtering criteria led to the identification of two compounds, TKI1 and TKI2 that were evaluated using in vitro cell-based RON inhibition assays. RESULTS: The results showed that TKI1 and TKI2 could reduce phosphorylation of RON. Both compounds showed inhibitory activity of the downstream mTOR pathway with no apparent effects on other signaling mediators in a dose-dependent manner. CONCLUSION: These compounds can provide a basis for developing novel anti-RON inhibitors applicable to cancer therapy using medicinal chemistry-oriented optimization strategies.


Asunto(s)
Proteínas Tirosina Quinasas Receptoras , Transducción de Señal , Ligandos
7.
Int J Microbiol ; 2021: 5573388, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34221021

RESUMEN

AIM: Klebsiella pneumoniae (K. pneumoniae) is an encapsulated Gram-negative bacterium that can lead to 14-20% of nosocomial infections. The ability of biofilm formation in this bacterium decreases the host immune response and antibiotic efficacy. This may impose a huge impact on patients and healthcare settings. This study aimed to evaluate the antibiotic resistance pattern and biofilm formation in K. pneumoniae strains isolated from two major Hamadan hospitals, west of Iran. METHODS: A total of 83 K. pneumoniae strains were isolated from clinical samples of patients in different wards of Hamadan hospitals from September 2018 to March 2019. Determination of antimicrobial susceptibility was performed using the disk diffusion method. Biofilm formation was evaluated by the crystal violet method. Data were analyzed by the SPSS software and chi-square test. RESULTS: The results showed that clinical samples included 18 urinary tract samples (22%), 6 wound samples (7%), 6 blood samples (7%), 17 tracheal tube aspiration samples (20%), 32 throat cultures (38%), 2 sputum samples (2.5%), and 2 abscess drain cultures (2.5%). High-level resistance to cefotaxime was detected in 92%, and all of isolates were susceptible to colistin. Biofilm formation was seen in 62 (75%) isolates. Strong biofilm formation was observed in 17 (20%) strains. A significant correlation was seen between biofilm formation and antibiotic resistance (P value <0.05). CONCLUSION: Our findings emphasize the need for proper diagnosis, control, and treatment of infections caused by K. pneumoniae especially in respiratory tract infections due to the strong biofilm formation and high antibiotic resistance in these strains.

8.
Urol J ; 19(3): 189-195, 2021 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-34247360

RESUMEN

BACKGROUND: Fibromodulin (FMOD) is a secretory protein which is considered a major component of extracellular matrix. Its dysregulation in different types of cancer implies it as a promising target for cancer therapy. Within the scope of its rather wide expression in different tumors, we studied expression of FMOD and effect of anti-FMOD antibody in bladder cancer cells in order to identify new target for diagnostic and therapeutic interventions. We report here for the first time the expression of FMOD in bladder cancer cell lines in comparison to the normal cell line and tissues. METHODS: A peptide-based produced anti-FMOD murine monoclonal antibody (mAb) (clone 2C2-A1) was applied for evaluation of FMOD expression in bladder cancer and normal tissues by immunohistochemistry (IHC) staining. Furthermore, the expression of FMOD was examined in human bladder cell lines, 5637 and EJ138, as well as a non-cancerous human cell line, human fetal foreskin fibroblast (HFFF), by immunocytochemistry (ICC) and flow cytometry. The apoptosis induction of anti-FMOD mAb was also evaluated in bladder cancer cells. RESULTS: IHC and ICC analyses revealed that the qualitative expression of FMOD in bladder cancer tissues and cell lines is higher than in normal tissues and cell lines. Flow cytometry analyses revealed that 2C2-A1 mAb could recognize FMOD expression in 84.05 ± 1.85%, 46.1 ± .4% , and 2.56 ± 1.26% of 5637, EJ138, and HFFF cells, respectively. An effective apoptosis induction was detected in 5637 and EJ138 cells with no significant effect on HFFF cell. CONCLUSION: To our knowledge, this is for the first time reporting surface expression of FMOD in bladder cancer. This significant surface expression of FMOD in bladder cancer with no expression in normal bladder tissues and the capacity of inducing apoptosis through directed targeting of FMOD with specific monoclonal antibody might candidates FMOD as a diagnostic marker as well as a potential immunotargeting with monoclonal antibody.


Asunto(s)
Carcinoma , Fibromodulina , Neoplasias de la Vejiga Urinaria , Anticuerpos Monoclonales , Fibromodulina/metabolismo , Humanos , Vejiga Urinaria
9.
BMC Pharmacol Toxicol ; 22(1): 32, 2021 06 08.
Artículo en Inglés | MEDLINE | ID: mdl-34103078

RESUMEN

BACKGROUND: Acinetobacter baumannii is an opportunistic pathogen that can cause several kinds of nosocomial infections. Increasing antibiotic resistance as well as identifying genetic diversity and factors associated with pathogenicity and prevalence of this bacterium is important. The aim of this study was the investigation of molecular typing, biofilm production, and detection of carbapenemase genes in multidrug-resistant Acinetobacter baumannii isolated from different infection sites using ERIC-PCR in Iran. METHODS: Forty isolates of A. baumannii were obtained from various wards of the central hospital, in the west of Iran. Phenotypic identification and genetic diversity, biofilm production assay, and detection of Carbapenemase genes carried out. RESULTS: Tracheal samples 26 (61.9 %) are the most frequent isolates, and 95 % of isolates were identified as MDR. 32.5 % of all A. baumannii strains were capable to form a strong biofilm. It was founded that antimicrobial resistance patterns had a significant relationship with strong biofilm formation (P = 0.001). Most frequencies of the studied genes were in the order of VIM (81 %), SPM (45.2 %), and IMP (35.7 %) genes. The VIM gene was the most frequent in all isolates which were significant (P = 0.006). 14 different ERIC-types were observed including 7 common types and 7 unique or single types. F type is the largest common type consisting of nine isolates and B, D, and E types contain two isolates separately. CONCLUSIONS: ERIC-PCR technique was used to genetically classify A. baumannii isolates as one of the most common microorganisms in nosocomial infections.


Asunto(s)
Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii , Proteínas Bacterianas/genética , beta-Lactamasas/genética , Acinetobacter baumannii/enzimología , Acinetobacter baumannii/genética , Acinetobacter baumannii/aislamiento & purificación , Acinetobacter baumannii/fisiología , Adolescente , Adulto , Biopelículas , Niño , Farmacorresistencia Bacteriana Múltiple , Femenino , Genes Bacterianos , Humanos , Irán , Masculino , Persona de Mediana Edad , Tipificación Molecular , Reacción en Cadena de la Polimerasa , Adulto Joven
10.
Int J Microbiol ; 2021: 3333240, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34987586

RESUMEN

BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) is known as a crucial zoonotic food-borne pathogen. A total of 257 raw chicken meat samples were collected from different markets in Hamadan, west of Iran, from January 2016 to May 2017. MATERIALS AND METHODS: The samples were cultured in selective and differential culture media, and the virulence genes of E. coli isolates were analyzed by PCR assay. The antibiotic resistance patterns of E. coli isolates were determined by the disk diffusion method. The genetic relatedness of the E. coli O157 isolates was analyzed by ERIC-PCR. RESULTS: In total, 93 (36% ± 3.12) of the isolates were identified as E. coli in this study. Based on serological and microbiological tests, 36 (38.7% ± 9.9), 7 (7.5% ± 5.35), and 12 (12.9% ± 6.81) of the E. coli isolates were characterized as STEC, enteropathogenic E. coli (EPEC), and attaching and effacing E. coli (AEEC) strains, respectively. A high level of resistance to nalidixic acid (91.4% ± 5.7), tetracycline (89.2% ± 6.31), ampicillin (82.8% ± 7.67), and trimotoprime-sulfametoxazole (71% ± 9.22) was detected among the E. coli isolates. The analysis of the ERIC-PCR results showed five different ERIC types among the E. coli O157 isolates. CONCLUSIONS: Based on our findings, control and check-up of poultry meats should be considered as a crucial issue for public health.

11.
J Pept Sci ; 27(3): e3292, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33200451

RESUMEN

To investigate whether peptide sequences with specific translocation across the gastrointestinal barrier can be identified as drug delivery vehicles, in vivo phage display was conducted. For this purpose, a random library of 12-mer peptides displayed on M13 bacteriophage was orally administered to mice followed by recovery of the phage particles from the blood samples after three consecutive biopanning rounds. The obtained peptide sequences were analyzed using bioinformatics tools and software. The results demonstrated that M13 bacteriophage bearing peptides translocate nonspecifically across the mice intestinal mucosal barrier deduced from random distribution of amino acids in different positions of the identified peptide sequences. The most probable reason for entering the phage particles into systemic circulation after oral administration of the peptide library can be related to the nanoscale nature of their structures which provides a satisfying platform for the purpose of designing nanocarriers in pharmaceutical applications.


Asunto(s)
Bacteriófago M13/metabolismo , Mucosa Intestinal/metabolismo , Péptidos/metabolismo , Administración Oral , Animales , Sistemas de Liberación de Medicamentos , Mucosa Intestinal/virología , Masculino , Ratones , Biblioteca de Péptidos , Péptidos/administración & dosificación
12.
Infect Drug Resist ; 13: 2365-2374, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32765011

RESUMEN

INTRODUCTION: The prevalence of nosocomial infections in patients hospitalized to three hospitals of Shahid Beheshti, Farshchian, and Be' saat in Hamadan was investigated for 2 years (2018 to 2020). MATERIALS AND METHODS: The samples were cultured and characterized using morphological and diagnostic biochemical tests. The analysis of the frequency of the isolates and their antibiotic resistance were calculated using SPSS (version 22) at a significant level of P-value < 0.05. RESULTS: Bacterial isolates were collected from the 1194 clinical specimens, of which 1394 were isolated from urine, 16 from CSF, and 588 from tracheal aspiration. Also, 654 (54.8%) isolates were obtained from females and 540 (45.2%) from males with the age range 15-73 years (P> 0.05). The results showed that 22.1% were gram-positive and 77.9% were gram-negative. In our study, the frequency of Klebsiella pneumoniae bacteria was higher than in some studies, and this indicates the genetic changes and resistance of this bacterium to many antibiotics. CONCLUSION: To prevent further spread of resistance, increase the effectiveness of antibiotics and prevent multidrug resistance, it is essential to establish a precise schedule for the use of antibiotics and assess the resistance pattern periodically in each region based on the antibiotic resistance pattern.

13.
Avicenna J Med Biotechnol ; 12(3): 165-171, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32695279

RESUMEN

BACKGROUND: Receptor tyrosine kinase-like Orphan Receptor 1 (ROR1) is one of the promising cell surface antigens for targeting cancer cells. The aim of this study was to evaluate ROR1 cell surface expression in bladder cancer cells using a murine anti-ROR1 monoclonal antibody (mAb) called 5F1-B10 as well as investigate its potential in apoptosis induction. METHODS: Expression of ROR1 in two human bladder cell lines, 5637 and EJ138, as well as a non-cancerous human cell line, Human Fetal Foreskin Fibroblast (HFFF), was examined by flow cytometry and immunocytochemistry. Immunohistochemical staining of cancer and normal bladder tissues was also performed. RESULTS: The flow cytometry results showed that 5F1-B10 mAb could recognize ROR1 molecules in 86.1% and 45.6% of 5637 and EJ138 cells, respectively. The expression level of ROR1 was 5.49% in HFFF cells. The immunocytochemistry and immunohistochemistry staining results also confirmed the presence of ROR1 on the surface of both bladder cancer cells and tissues, respectively. The obtained data from apoptosis assay demonstrated that 5F1-B10 mAb could induce apoptosis in both 5637 and EJ138 cell lines. CONCLUSION: Taken together, our finding indicates the role of ROR1 in bladder cancer cell survival and suggests this receptor might be a promising target for developing novel therapeutic agents against bladder carcinoma.

14.
Infect Disord Drug Targets ; 20(5): 758-762, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31889501

RESUMEN

BACKGROUND: Pseudomonas aeruginosa is a gram-negative non-glucose fermenting aerobic bacteria and an opportunistic pathogen in humans and animals. The present study was carried out to investigate the distribution of virulence factors and antibiotic resistance properties of P. aeruginosa isolated from patients and intensive care unit (ICU) environment. MATERIAL AND METHODS: A total of 116 P. aeruginosa isolated from patients and ICU environment were collected from Besat hospital in Hamadan, the West of Iran. P. aeruginosa isolates were analyzed based on the presence of the virulence factors encoding genes included exoA, exoS, exoU, and algD using polymerase chain reaction (PCR). Antimicrobial susceptibility test was performed using a disk diffusion method. RESULTS: The results showed the prevalence of exoA 33 (56.9%), exoS 21 (36.20%), exoU 37 (63.8%), and algD 35 (60.34%) genes in ICU environment P. aeruginosa strains and exo A 23 (39.25%), exoS 25 (43.1%), exoU 40(68.98%), and algD 25 (43.1%) genes in clinical isolates of P. aeruginosa. High resistance levels of the clinical and ICU environment isolate to ampicillinsulbactam (100%), were also observed. CONCLUSION: Our findings should raise awareness about antibiotic resistance in hospitalized patients in Iran. Clinicians should exercise caution in prescribing antibiotics, especially in cases of human infections.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/clasificación , Factores de Virulencia/genética , Ampicilina/farmacología , Proteínas Bacterianas/genética , Pruebas Antimicrobianas de Difusión por Disco , Microbiología Ambiental , Humanos , Unidades de Cuidados Intensivos , Irán , Reacción en Cadena de la Polimerasa , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/aislamiento & purificación , Sulbactam/farmacología
15.
Artículo en Inglés | MEDLINE | ID: mdl-31198116

RESUMEN

INTRODUCTION: Antibiotic resistance and extensive use of antibiotics are amongst the major causes of failure in antibiotic treatment. The purpose of this study was to investigate antibiotic resistance patterns and to identify resistance genes of quinolones and colistin in Escherichia coli. There are a very few patents on E. coli isolated from colorectal cancer. So, this study demonstrates that some bacteria resistant to ciprofloxacin have not resistance genes.Moreover, new patterns for E. coli are presented for isolates of patients with colorectal cancer. MATERIALS AND METHODS: Of the three healthy people, inflammatory bowel diseases (IBD) patients and colorectal cancer patients, 40 E. coli strains isolated after confirmation by biochemical and molecular methods. The susceptibility of isolates to antibiotics was investigated using disk diffusion test. After deoxyribonucleic acid (DNA) extraction, polymerase chain reaction (PCR) was used to identify genes encoding resistance to ciprofloxacin (qnr A, qnr B) and colistin (mcr-1). RESULTS: The results showed that E. coli isolates from colorectal cancer patients had the highest resistance to piperacillin (67.5%), ceftazidime (47.5%), and cefepime (42.5%). Also, E. coli strains isolated from IBD patients showed resistance to antibiotic ceftazidime 13%. More than 95% of E. coli strains isolated from healthy people were susceptible to antibiotics. Based on the results, 18 (15%) E. coli strains showed resistance to ciprofloxacin. The qnr A gene was detected in 61.11% isolates; however, qnr B was detected in 9 (50%) isolates. Isolates resistant to colistin were not observed. CONCLUSION: These findings indicate increased resistance of E. coli to ciprofloxacin in comparison with prior studies. Further research in this field will increase our knowledge and more effective exposure to the antibiotic resistance of the pathogenic microorganisms.


Asunto(s)
Colistina/farmacología , Neoplasias Colorrectales/microbiología , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Quinolonas/farmacología , Antibacterianos/farmacología , Farmacorresistencia Bacteriana/efectos de los fármacos , Farmacorresistencia Bacteriana/genética , Escherichia coli/aislamiento & purificación , Proteínas de Escherichia coli/genética , Voluntarios Sanos , Humanos , Enfermedades Inflamatorias del Intestino/microbiología , Mucosa Intestinal/microbiología , Irán
16.
Chem Biol Drug Des ; 95(2): 279-290, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31661597

RESUMEN

Recently, multi-target directed ligands have been of research interest for multifactorial disorders such as Alzheimer's disease (AD). Since H3 receptors (H3 Rs) and cholinesterases are involved in pathophysiology of AD, identification of dual-acting compounds capable of improving cholinergic neurotransmission is of importance in AD pharmacotherapy. In the present study, H3 R antagonistic activity combined with anticholinesterase properties of two previously computationally identified lead compounds, that is, compound 3 (6-chloro-N-methyl-N-[3-(4-methylpiperazin-1-yl)propyl]-1H-indole-2-carboxamide) and compound 4 (7-chloro-N-[(1-methylpiperidin-3-yl)methyl]-1,2,3,4-tetrahydroisoquinoline-2-carboxamide), was tested. Moreover, molecular docking and binding free energy calculations were conducted for binding mode and affinity prediction of studied ligands toward cholinesterases. Biological evaluations revealed inhibitory activity of ligands in nanomolar (compound 3: H3 R EC50  = 0.73 nM; compound 4: H3 R EC50  = 31 nM) and micromolar values (compound 3: AChE IC50  = 9.09 µM, BuChE IC50  = 21.10 µM; compound 4: AChE IC50  = 8.40 µM, BuChE IC50  = 4.93 µM) for H3 R antagonism and cholinesterase inhibition, respectively. Binding free energies yielded good consistency with cholinesterase inhibitory profiles. The results of this study can be used for lead optimization where dual inhibitory activity on H3 R and cholinesterases is needed. Such ligands can exert their biological activity in a synergistic manner resulting in higher potency and efficacy.


Asunto(s)
Inhibidores de la Colinesterasa/farmacología , Colinesterasas/efectos de los fármacos , Antagonistas de los Receptores Histamínicos H3/farmacología , Receptores Histamínicos H3/efectos de los fármacos , Inhibidores de la Colinesterasa/química , Simulación por Computador , Antagonistas de los Receptores Histamínicos H3/química , Técnicas In Vitro , Ligandos , Relación Estructura-Actividad
17.
Bioorg Chem ; 94: 103374, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31699389

RESUMEN

Platelet-derived growth factor (PDGF) is a family of growth factors with mitogenic and chemotactic activity. However, uncontrolled and overactivated PDGF signaling has been implicated in a variety of diseases, such as cancers and atherosclerosis. In this context, inhibition of PDGF-PDGFR signaling is of paramount importance in progression of such diseases. The purpose of the current study was to identify novel PDGF-B inhibitors using virtual screening methods. To this end, a combination of molecular modeling techniques such as molecular docking and dynamics simulation, as well as drug likeness filtering criteria, was applied to select anti-PDGF peptidomimetic candidates based on crystallography solved structure of an anti-PDGF-B monoclonal antibody named, MOR8457. In vitro biological assays of the selected compounds revealed two of them being active at micromolar IC50 concentrations. The presented work can provide a framework for systematic peptidomimetic identification for anti-PDGF-B agents from large chemical libraries.


Asunto(s)
Anticuerpos Monoclonales/farmacología , Descubrimiento de Drogas , Proteínas Proto-Oncogénicas c-sis/antagonistas & inhibidores , Bibliotecas de Moléculas Pequeñas/farmacología , Anticuerpos Monoclonales/química , Células Cultivadas , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Humanos , Modelos Moleculares , Estructura Molecular , Bibliotecas de Moléculas Pequeñas/síntesis química , Bibliotecas de Moléculas Pequeñas/química , Relación Estructura-Actividad
18.
Hum Vaccin Immunother ; 15(9): 2178-2182, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31267848

RESUMEN

Streptococcus pneumoniae is a common cause of community-acquired pneumonia, meningitis, and otitis media in children. The aim of this study was to determine the prevalence of nasopharyngeal carriage of Streptococcus pneumoniae among children in the city of Hamadan, west of Iran. In this cross-sectional study, 532 students aged 7 to 14 years old from Hamadan were enrolled during the period from February to April 2016. Children were recruited using multi-stage sampling method. Informed consent form was obtained from parents of children. A researcher developed checklist was completed for every child by interviewer and samples of the throat of children were taken by swap method from the nasopharyngeal area. Descriptive statistics and chi square test were used to describe the study population. This study was approved by the Committee on Ethics of Hamadan University of Medical Sciences (IR.UMSHA.REC.1394.66). Prevalence of nasopharyngeal carriage of S. pneumoniae in children was 12.03% (95%CI: 9.38-15.10). About 37% (196 persons) of study population were male and 63% were female. Sixty four percent (345 people) of the studied population were from district two in Hamadan and others from District one. Prevalence of nasopharyngeal carriage of S. pneumoniae by sex was 13.77% (95% CI: 9.27-19.40) in males and 11.02 % (95% CI: 7.87-14.85) in females (P = 0.345). Considering the high prevalence of nasopharyngeal carriage of Streptococcus pneumoniae in children studied in Hamadan, pneumococcal conjugate vaccine (PCV) is recommended to be integrated into the Iran's National Immunization Program.


Asunto(s)
Portador Sano/epidemiología , Nasofaringe/microbiología , Infecciones Neumocócicas/epidemiología , Vacunas Neumococicas/administración & dosificación , Streptococcus pneumoniae/aislamiento & purificación , Adolescente , Portador Sano/microbiología , Niño , Estudios Transversales , Femenino , Humanos , Programas de Inmunización , Irán/epidemiología , Masculino , Infecciones Neumocócicas/prevención & control , Prevalencia , Serogrupo , Encuestas y Cuestionarios , Vacunas Conjugadas/administración & dosificación
19.
Gastroenterol Hepatol Bed Bench ; 12(1): 52-59, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30949320

RESUMEN

AIM: This study determined the genes encoding the binding and receiving factors of iron and microbial biofilm in E. coli strains isolated from mucosal samples of patients with colorectal cancer and inflammation of the colorectal compared to healthy people. BACKGROUND: Colorectal cancer is one of the most important malignancies in recent years. Escherichia coli is the most important infectious agents associated with colorectal cancer that has numerous virulence factors such as iron uptake and adhesion factors included in the process of inflammation and colorectal cancer. METHODS: Of the three healthy, inflammatory bowel diseases and colorectal cancer groups, 40 Escherichia coli strains isolated after confirmation by biochemical and molecular methods. After determining the isolates phylogroups, the frequency of genes was measured by PCR method. The biofilm formation of isolates was performed using Crystal Violet method. RESULTS: In the determination of the bacteria phylogroups, the colorectal cancer isolates had a maximum incidence of phylogroups B2 and A. In the analysis of fimH, papA, papC, iutA, ireA and fyuA genes, the highest frequency was observed in these two phylogroups. The presence of ireA gene in bacterial isolates from three groups showed a significant difference (P value: 0.004). There was also no significant difference in biofilm productions in Escherichia coli strains isolated from the three groups. CONCLUSION: Unlike previous studies focusing solely on Escherichia coli toxins, we found that iron absorption and adhesion factors could be effective in developing inflammatory bowel diseases and colorectal cancer. It was also determined that biofilm formation is a specific characteristic of Escherichia coli isolated from the healthy colon.

20.
Pharmacol Ther ; 200: 69-84, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31028835

RESUMEN

Since the discovery of the histamine H3 receptor in 1983, tremendous advances in the pharmacological aspects of H3 receptor antagonists/inverse agonists have been accomplished in preclinical studies. At present, there are several drug candidates that reached clinical trial studies for various indications. However, entrance of these candidates to the pharmaceutical market is not free from challenges, and a variety of difficulties is engaged with their developmental process. In this review, the potential role of H3 receptors in the pathophysiology of various central nervous system, metabolic and allergic diseases is discussed. Thereafter, the current status for H3 receptor antagonists/inverse agonists in ongoing clinical trial studies is reviewed and obstacles in developing these agents are emphasized.


Asunto(s)
Antagonistas de los Receptores Histamínicos H3/uso terapéutico , Receptores Histamínicos H3/metabolismo , Animales , Agonismo Inverso de Drogas , Humanos
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