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Reconstruction of the lip is a necessary procedure when lip tumors are excised. Although many good techniques have been described, they often have disadvantages such as necrosis and extensive suture lines. In our approach, we aim to minimize the suture line and avoid tissue necrosis for medium-sized lip defects (30-80 %). This is a surgical technique report from a single center. After tumor resection, we made a bilateral 15 mm horizontal skin and mucosa incision from the angles of the lip to the lateral sides. The mucosa and skin were dissected from the underlying muscle, and the muscle was cut approximately 15 mm on each side. The lip defect was then closed and sutured in four layers. Finally, the released mucosa was sutured to the corner of the incised skin. We followed the patients for 36 months and found that their speech intelligibility, sensation, mobility, and aesthetic satisfaction were preserved. The scars were also less pronounced compared to flaps, and there were no signs of edema or drooling. In conclusion, our technique offers many advantages for moderate defects of lower lip tumors. By avoiding the use of flaps, we eliminate the complications associated with flap surgery while achieving aesthetically satisfactory results. However, further evaluation by other surgeons is necessary to fully examine the technique's benefits.
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Neoplasias Labiais , Procedimentos de Cirurgia Plástica , Humanos , Lábio/cirurgia , Neoplasias Labiais/cirurgia , Retalhos Cirúrgicos , Necrose/cirurgiaRESUMO
Flexion-relaxation phenomenon (FRP) is a well-known phenomenon in spinal extensor muscles. According to the literature, prolonged flexed posture leads to creep phenomenon and affects the active and passive neuromuscular control of the spinal column. The purpose of this study was to investigate FRP occurrence in elite cyclists that prolonged flexion posture is an integral part of their professional life. Their muscles' contraction pattern during forward bending was also compared. Electromyography (EMG) was recorded during flexion and extension from standing position in thoracic erector spinae (TES), lumbar erector spinae (LES) and gluteus maximus (Gluteus max) in 15 healthy male elite cyclists. In addition, the kinematic data related to the trunk angles were simultaneously recorded by a motion analysis system. Two-way ANOVA was used to assess the effects of muscle group and direction of movement on maximum amplitude of EMG activity. Among 15 cyclists, FRP was detectable in 60%, 87% and 73% of the participants in TES, LES and Gluteus max, respectively, and happened between 74% and 82% of the trunk flexion. There was no statistically significant difference in onset and offset of muscles FRP. Despite prolong hyper kyphotic posture, FRP was identifiable in TES, LES and Gluteus max muscles of elite cyclists.
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Reactive oxygen species are associated with cryodamage and may be a factor causing or exacerbating cellular cryodamage during freezing and thawing processes. Induction of sublethal oxidative stress as a new approach for preconditioning of sperm improves the cryo-resistance of sperm. The aim of this study was to investigate effects of sublethal concentrations of xanthine oxidase (XO), which induces oxidative stress before cryopreservation on values for semen quality variables of rooster sperm post-thawing. Semen samples were collected from 15 roosters and treated with different concentrations of XO [XO-0, XO-0.005, XO-0.05, XO-0.5, XO-5, and XO-50 U/ml]; then, the effects of treatments with XO as sublethal stressors, were examined. Results indicated the XO-0.5 and XO-5 treatments resulted in a greater percentage of sperm total motility, progressive motility, viability, and membrane functionality compared to other groups. There was no difference after treatments with XO-0, XO-0.005, and XO-0.05 on sperm total motility, membrane functionality, apoptosis, mitochondria activity, and viability. There was a greater percentage of mitochondria activity in sperm of the XO-0.05, XO-0.5, and XO-5 groups. Furthermore, there was the greatest concentration of malondialdehyde (MDA) in samples of the XO-50 group. Values for sperm abnormal morphology, acrosome integrity, and DNA fragmentation were not different among samples post-thawing. Sperm treated with XO-0.5 and XO-5 had a greater fertilization capacity than those of the control group. In conclusion, treatment of sperm with 0.5 and 5 U/ml XO as inducers of mild oxidative stress before cryopreservation, improved several function quality indices of sperm post-thawing.
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Galinhas/fisiologia , Criopreservação/veterinária , Estresse Oxidativo , Análise do Sêmen/veterinária , Sêmen/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Xantina Oxidase/efeitos adversos , Animais , Masculino , Preservação do Sêmen/veterinária , Xantina Oxidase/administração & dosagemRESUMO
Malformations of the maxillofacial region has disturbing psychosocial effects and causes enormous socioeconomic concerns. The management of maxillofacial defects caused by congenital anomalies, trauma, osteoporotic fractures, periodontitis, or cancer treatment is challenging for oral and maxillofacial surgeons. Numerous approaches have been recommended for the managing of these deficiencies. The traditional treatment for maxillofacial defects or their repair is an intricate process by autologous bone grafts from the scapula, ribs, fibula, or iliac crest origins. Regenerative medicine is well thought-out as a perfect substitute approach for autologous bone grafts to renovate bone deficiencies. The use of stem cells has improved results and offered a technique to reconstruct craniofacial bone defects. The field of tissue engineering for the regeneration of maxillofacial needs integration of biochemical and biomaterial engineering aspects with cell transplantation to generate better-quality biomimetic scaffolds, prevascularize three-dimensional (3D) tissue structures, and engineer the composite interface of diverse facial tissues. In this review, we have discussed the application of different adult stem cells to repair oral and maxillofacial defects in animal models and clinical trials.
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Medicina Regenerativa , Engenharia Tecidual , Animais , Transplante Ósseo , Fíbula , Humanos , Células-TroncoRESUMO
1. This study examined the expression of genes related to appetite-regulating neuropeptides in the hypothalamus of broiler and layer chicks (Gallus gallus) after intraperitoneal (IP) injection of lipopolysaccharide (LPS). 2. Both broiler and layer chicks received (n = 10 per group) LPS at doses of 0 and 200 µg and feed intake was measured up to 6 h after injection. In a further experiment, (n = 8 per group) mRNA abundance of some hypothalamic neuropeptides was measured 2 h after injection. The rectal temperature of each chick was measured before and 2 h post-injection. 3. Feed intake was significantly decreased by LPS from 2 h after injection and thereafter, while the rectal temperature did not change. 4. LPS decreased the expression of appetite-enhancing neuropeptides: neuropeptide Y (NPY) and agouti-related peptide (AgRP) in broilers and, NPY in layer chicks. The expression of appetite-suppressing neuropeptides (corticotrophin-releasing factor (CRF), proopiomelanocortin (POMC) and, cocaine and amphetamine regulated-transcript (CART) was not changed in broilers, while CRF tended to decrease and POMC was significantly decreased in layers. The abundance of the cytokine tumour necrosis factor-alpha (TNF-α) did not change in broilers but was decreased in layers. 5. The findings indicated that the reduction in gene expression of hypothalamic appetite-enhancing neuropeptides NPY and AgRP is responsible for anorexia caused by LPS at a dose that did not influence body temperature.
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Galinhas , Neuropeptídeos , Animais , Regulação do Apetite , Temperatura Corporal , Galinhas/genética , Galinhas/metabolismo , Ingestão de Alimentos , Hipotálamo/metabolismo , Lipopolissacarídeos , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , TemperaturaRESUMO
Burns are considered an important preventable fraction of injuries in low and middle-income countries, and are still a leading cause of death in Iran. This study investigates features of burns in Sina Hospital's Burn Centre in East Azerbaijan Province in order to calculate survival and mortality rates as well as factors affecting mortality in this centre. In this cross-sectional study, demographic characteristics of patients such as age, sex, cause of burns, type of burns, length of stay (LOS) in the hospital, total body surface area (TBSA), anatomic distribution of burn, mortality rate and final status of patients at the time of discharge from hospital (recovery, death) were investigated. The total mortality rate was 6.84%. Hot liquid burns and gas cylinder explosion burns were among the most common. Burns on multiple regions of the body (45.9%) and pelvic and lower limb burns (22%) constituted the next most common injury. In the TBSA index, compared to reference categories (extent of burn less than 50 percent), the categories of 50-59, 60-69, 70-79, 80-89 and over 90 percent indicated lowest survival based on the Log-Rank test. Hazard ratio for burns greater than 10% was 15.33 fold. Total body surface area burned of over 10% constantly increases the instantaneous risk of mortality therefore there is a need to enhance the quality of care provided to burn victims.
Les brûlures sont considérées comme des accidents hautement évitables dans les pays à IDH bas et moyen. Elles restent une cause majeure de décès en Iran. Cette étude détaille les caractéristiques des brûlés hospitalisés dans le CTB de l'hôpital Sina (province iranienne d'est Azerbaïdjan) afin d'en évaluer la mortalité et les facteurs l'influençant. Dans cette étude transversale, nous avons analysé l'âge et le sexe des patients, la cause de la brûlure, la surface atteinte et la localisation, la durée d'hospitalisation et la mortalité. Celle ci était de 6,84%, elle était plus élevée au-delà de 50% SCT brûlée (Log Rank). Le risque de mortalité est multiplié par 15,33 au-delà de 10% de SCT, limite de surface nécessitant donc des soins spécifiques. Les 2 causes les plus fréquentes étaient les ébouillantements et les explosions de gaz. Les atteintes disséminées (45,9%) ainsi que celles de la région pelviennes et des membres inférieurs (22%) prédominaient.
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AIMS: The current study aimed to investigate the ability of lactic acid bacteria (LABs) in removing four polycyclic aromatic hydrocarbons (PAHs) namely, benzo(a)pyrene (BaP), benz(a)anthracene (BaA), chrysene (Chr) and benzo(b)fluoranthene (BbF) from contaminated phosphate buffer saline (PBS). METHOD AND RESULTS: The effect of initial PAH concentrations (5, 10, 15, 20 µg ml-1 ), bacterial population (107 , 108 , 109 , 1010 CFU per ml) and pH (3, 5, 7) was studied to evaluate bacterial binding ability. All the tested bacteria could remove BaA, Chr, BbF and BaP from phosphate buffer solution and in almost all assays, removing of PAHs was as follows: BaP>Chr>BaA>BaF. Bifidobacterium lactis BB-12 had the lowest binding rate for all four PAHs, while the highest binding ability was related to Lactobacillus acidophilus LA-5. Moreover, cell viability was not required for the binding ability and even acid-treated, heat-treated and ultrasonic-treated bacterial cells showed more binding ability. The results showed that the bacteria-PAH complex was irreversible after washing with PBS. CONCLUSIONS: The removal of PAHs was significantly related to pH of media, strains of bacteria, type and concentration of PAHs SIGNIFICANCE AND IMPACT OF THE STUDY: This study has been focused on the reduction of polycyclic aromatic hydrocarbons using LABs and probiotics. Our results showed that not only live strains but also inactivated tested strains are able to remove PAHs from aqueous media, presenting new methods to diminish the amount of these contaminants in foods. Furthermore, the results of this study can be used in future research on evaluating the effects of oral administration of probiotic supplements and even dead probiotic strains on reducing PAHs in humans.
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Lactobacillales , Hidrocarbonetos Policíclicos Aromáticos , Lactobacillales/química , Lactobacillales/metabolismo , Lactobacillales/fisiologia , Hidrocarbonetos Policíclicos Aromáticos/isolamento & purificação , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , ProbióticosRESUMO
To evaluate the effect of microsurgical inguinal varicocelectomy with testicular delivery on semen parameters. A total of 416 patients, diagnosed with grade III varicocele, were randomised into two groups. One group underwent microsurgical inguinal varicocelectomy without testicular delivery. For the other group, testicular delivery and ligation of gubernacular and all collateral veins were performed. A semen analysis was performed before and 6 months after the procedure. Mean age of the patients in the case and control groups was 27.3 ± 6.1 years and 25.9 ± 4.6 years respectively (p = .1). The total number of recurrence after 6 months in the conventional and testicular delivery groups was 13 (6.5%) and 3 (1.5%) (p < .05). No case of hydrocele formation was observed in any of the groups. All sperm parameters were improved 6 months after the surgery in both groups. But comparing the mean improved difference between the two groups revealed a significant difference in improvement in sperm motility for patients who had undergone varicocelectomy with testicular delivery (p = .05). Microsurgical inguinal varicocelectomy is a safe and efficient technique with a minimum chance of post-operative complications and recurrence and also may have role in improvement of sperm motility compared with conventional techniques.
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OBJECTIVE: To assess the frequency of bacterial agents in chronic suppurative otitis media and the antibiotic susceptibility patterns of isolates among patients. METHODS: A total of 185 patients clinically diagnosed with chronic suppurative otitis media were interviewed and middle-ear effusion samples were collected using sterile swabs. All bacterial isolates were identified by conventional microbiological methods. Antibiotic susceptibility patterns of the isolates were determined by Kirby-Bauer disc diffusion. RESULTS: Staphylococci spp. (64.9 per cent) were the most prevalent bacteria isolated, followed by Klebsiella spp. (12.9 per cent) and Pseudomonas aeruginosa (10.3 per cent). The most effective antibiotic for treatment of bacterial chronic suppurative otitis media was ciprofloxacin. Statistical analysis showed no significant difference in bacterial infestations among chronic suppurative otitis media patients and the antimicrobial susceptibility patterns of the bacterial isolates based on gender and age (p > 0.05). CONCLUSION: Our findings highlight the importance of a continuous and periodic evaluation of the bacteriological profile and antibiotic susceptibility patterns in chronic suppurative otitis media patients for efficacious treatment of the infection.
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Antibacterianos/uso terapêutico , Bactérias/isolamento & purificação , Farmacorresistência Bacteriana , Otite Média Supurativa/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bactérias/efeitos dos fármacos , Criança , Pré-Escolar , Doença Crônica , Estudos Transversais , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Otite Média Supurativa/tratamento farmacológico , Adulto JovemRESUMO
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major causes of hospital- and community-acquired infections worldwide. Although S. aureus rarely accounts for urinary tract infections (UTI), untreated UTI can lead to several complications. For decades vancomycin has been used for the treatment of MRSA infections. This study was performed to assess the in vitro activity of vancomycin, tigecycline, linezolid and quinupristin/dalfopristin against MRSA isolates from UTI patients. Thirty MRSA strains from 54 S. aureus isolates were isolated from patients with UTI. The antimicrobial susceptibility patterns of the strains were determined by the Kirby-Bauer disk diffusion and broth microdilution methods. PCR assays were used to detect the vanA gene. The MRSA isolates resistant to vancomycin were confirmed using the broth microdilution method. The results revealed that the MRSA isolates were 100% susceptible to linezolid and quinupristin/dalfopristin but 93.3% susceptible to vancomycin and tigecycline respectively. The broth microdilution method confirmed two MRSA strains (6.6%) to be resistant to vancomycin and tigecycline. The study identified vancomycin resistance among the MRSA isolates from UTI patients. This vancomycin resistance in MRSA isolates poses a challenge in managing S. aureus infections. Our study's results highlight the need to correctly identify patients in whom last-resort therapy such as linezolid and quinupristin/dalfopristin should be administered.
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BACKGROUND: Urinary tract infection (UTI) is one of the most frequent types of nosocomial and community acquired infections in humans. Management of multidrug-resistant Enterococci UTI due to the limited therapeutic options is a great challenge for physicians and clinical microbiologists. The role of bacterial biofilms in recurrent urinary tract infections and antimicrobial resistance has great importance for public health. The aim of this study was to investigate the antibiotic susceptibility pattern as well as the phenotypic and genotypic biofilm formation ability of Enterococci isolates from patients with UTI. METHODS: A total of 57 isolates of Enterococci were collected from patients with UTI. Enterococcus species were identified using conventional microbiological methods. The antibiotic susceptibility patterns of the isolates were determined by the Kirby-Bauer disk-diffusion. The Modified Congo red agar (MCRA) and Microtiter plate methods used to assess the ability of biofilm formation. All enterococcal isolates were examined for determination of biofilm-related genes, esp, asa1 and ebpR using PCR method. RESULTS: Of 57 enterococcal isolates, 85.9% were recognized as E. faecalis and 14.1% of them were E. faecium. According to our results, linezolid, chloramphenicol and nitrofurantoin were the most effective agents against Enterococcus species. Overall, 26.5% of E. faecalis and 75% of E. faecium isolates were biofilm producers, respectively. Resistance to some antibiotics including penicillin G, ampicillin, vancomycin, nitrofurantoin and chloramphenicol, and ciprofloxacin was significantly higher among biofilm producers than non-biofilm producers Enterococci. The esp, asa1 and ebpR genes were present in 84.2%, 91.2% and 100% isolates. In this study, there was not a significant relationship between presence of these genes and biofilm formation. CONCLUSION: Our findings reinforce the role of biofilm formation in resistance to antimicrobial agents. Quinupristin/dalfopristin, tetracycline and rifampin may be used as an effective treatment for UTI caused by biofilm producers Enterococci. Our results suggest that biofilm formation is complex and depends on various factors but not just esp, asa1 and ebpR genes in Enterococcus strains.
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Biofilmes/crescimento & desenvolvimento , Enterococcus/genética , Enterococcus/metabolismo , Genótipo , Infecções por Bactérias Gram-Positivas/microbiologia , Fenótipo , Infecções Urinárias/microbiologia , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Cloranfenicol/farmacologia , Farmacorresistência Bacteriana , Enterococcus/efeitos dos fármacos , Enterococcus/isolamento & purificação , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/isolamento & purificação , Enterococcus faecium/efeitos dos fármacos , Enterococcus faecium/isolamento & purificação , Genes Bacterianos/genética , Humanos , Irã (Geográfico) , Linezolida/farmacologia , Testes de Sensibilidade Microbiana , Nitrofurantoína/farmacologia , Reação em Cadeia da Polimerase , Infecções Urinárias/tratamento farmacológico , Fatores de Virulência/genéticaRESUMO
This study presents an agent-based simulation modeling in an emergency department. In a traditional approach, a supervisor (or a manager) allocates the resources (receptionist, nurses, doctors, etc.) to different sections based on personal experience or by using decision-support tools. In this study, each staff agent took part in the process of allocating resources based on their observation in their respective sections, which gave the system the advantage of utilizing all the available human resources during the workday by being allocated to a different section. In this simulation, unlike previous studies, all staff agents took part in the decision-making process to re-allocate the resources in the emergency department. The simulation modeled the behavior of patients, receptionists, triage nurses, emergency room nurses and doctors. Patients were able to decide whether to stay in the system or leave the department at any stage of treatment. In order to evaluate the performance of this approach, 6 different scenarios were introduced. In each scenario, various key performance indicators were investigated before and after applying the group decision-making. The outputs of each simulation were number of deaths, number of patients who leave the emergency department without being attended, length of stay, waiting time and total number of discharged patients from the emergency department. Applying the self-organizing approach in the simulation showed an average of 12.7 and 14.4% decrease in total waiting time and number of patients who left without being seen, respectively. The results showed an average increase of 11.5% in total number of discharged patients from emergency department.
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Simulação por Computador , Tomada de Decisões Assistida por Computador , Técnicas de Apoio para a Decisão , Serviço Hospitalar de Emergência/organização & administração , APACHE , Eficiência Organizacional , Humanos , Modelos Organizacionais , Pacientes , Admissão e Escalonamento de Pessoal , Reprodutibilidade dos Testes , Fatores de Tempo , Estudos de Tempo e Movimento , TriagemRESUMO
This study presents an agent-based simulation modeling in an emergency department. In a traditional approach, a supervisor (or a manager) allocates the resources (receptionist, nurses, doctors, etc.) to different sections based on personal experience or by using decision-support tools. In this study, each staff agent took part in the process of allocating resources based on their observation in their respective sections, which gave the system the advantage of utilizing all the available human resources during the workday by being allocated to a different section. In this simulation, unlike previous studies, all staff agents took part in the decision-making process to re-allocate the resources in the emergency department. The simulation modeled the behavior of patients, receptionists, triage nurses, emergency room nurses and doctors. Patients were able to decide whether to stay in the system or leave the department at any stage of treatment. In order to evaluate the performance of this approach, 6 different scenarios were introduced. In each scenario, various key performance indicators were investigated before and after applying the group decision-making. The outputs of each simulation were number of deaths, number of patients who leave the emergency department without being attended, length of stay, waiting time and total number of discharged patients from the emergency department. Applying the self-organizing approach in the simulation showed an average of 12.7 and 14.4% decrease in total waiting time and number of patients who left without being seen, respectively. The results showed an average increase of 11.5% in total number of discharged patients from emergency department.
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Humanos , Simulação por Computador , Tomada de Decisões Assistida por Computador , Técnicas de Apoio para a Decisão , Serviço Hospitalar de Emergência/organização & administração , APACHE , Eficiência Organizacional , Modelos Organizacionais , Pacientes , Admissão e Escalonamento de Pessoal , Reprodutibilidade dos Testes , Estudos de Tempo e Movimento , Fatores de Tempo , TriagemRESUMO
High-mobility group AT-hook2 (HMGA2), involved in epithelial mesenchymal transition (EMT) process, has a pivotal role in lung cancer metastasis. Lung cancer therapy with HMGA2 suppressing small interfering RNA (siRNA) has been introduced recently while doxorubicin (DOX) has been used as a frequent cancer chemotherapy agent. Both reagents have been faced with obstacles in clinic which make them ineffective. NanoParticles (NPs) provided a platform for efficient co delivery of the anticancer drugs. The aim of this study was production and in vitro characterization of different pharmacological groups (siRNA, DOX or siRNA-DOX) of carboxymethyl dextran thrimethyl chitosan nanoparticles (CMDTMChiNPs) on cytotoxicity, gene expression, apoptosis and migration of metastatic lung cancer cell line (A-549). CMDTMChiNPs were synthesized and encapsulated with siRNA, DOX or siRNA-DOX. Then the effects of HMGA2 siRNA and DOX co delivery was assessed in A549 viability and target genes (HMGA2, Ecadherin, vimentin and MMP9) by MTT and real time PCR, respectively. In addition capability of apoptosis induction and anti-migratory features of formulated NPs were analyzed by flowcytometry and wound healing assays. SiRNA-DOX-CMDTM ChiNPs approximate size were 207±5 with poly dispersity index (PDI) and zeta potential of 0.4 and 16.3±0.3, respectively. NPs loaded with DOX and siRNA were the most efficient drug formulations in A549 cell cytotoxicity, altering of EMT markers, apoptosis induction and migration inhibition. Generally our results showed that co delivery of HMGA2 siRNA and DOX by novel designed CMDTMChiNPs is a new therapeutic approach with great potential efficiency for lung cancer treatment.
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Antineoplásicos/química , Quitosana/análogos & derivados , Doxorrubicina/química , Portadores de Fármacos/química , Nanopartículas/química , RNA Interferente Pequeno/química , Células A549 , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Caderinas/genética , Caderinas/metabolismo , Movimento Celular/efeitos dos fármacos , Quitosana/química , Doxorrubicina/toxicidade , Proteína HMGA2/antagonistas & inibidores , Proteína HMGA2/genética , Proteína HMGA2/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Microscopia Eletrônica de Varredura , RNA Interferente Pequeno/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Espectroscopia de Infravermelho com Transformada de Fourier , Vimentina/genética , Vimentina/metabolismoRESUMO
Inflammation is inseparable part of different diseases especially cancer and autoimmunity. During inflammation process toll like receptor 4(TLR4) responds to lipopolysaccharide (LPS), one of the bacterial components, and TLR4 signaling leads to interleukine-1 receptor associated kinase-1 (IRAK1) and tumor necrosis factor (TNF) receptor associated factor6 (TRAF6) activation which ultimately results in nuclear factor- ĸB (NF-ĸB) activation as the main transcription factor of inflammatory cytokines. Conversely, NF-ĸB over activation induces miR-146a in innate immune cells which can consequently reduce TRAF6, IRAK1, and NF-ĸB activation in a negative feedback. G2013 is a novel designed non-steroidal anti-inflammatory drug (NSAID) which was recently shown to be effective in experimental autoimmune encephalomyelitis (EAE) mouse model. The aim of this study was to evaluate G2013 effects on inflammatory (IRAK1 and TRAF6) and anti-inflammatory (miR-146a) factors of TLR4 signaling pathway. For this purpose, cytotoxicity of G2013 has been evaluated by MTT assay. Expression level of miR-146a in PBMCs and IRAK1 along with TRAF6 in HEK-293 TLR4 cells have been determined using real time PCR. Our results showed that IC50 of G2013 was 25µg/ml, thus 5 and 25 µg/ml concentrations used for further treatments as low dose and high dose concentrations. Our results showed that IRAK1 expression reduced between 5 to 8 fold after treatment by G2013 in a dose dependent manner (p<0.001). In parallel TRAF6 expression declined between 3 to 10 fold dose dependently (p<0.05). However, miR-146a expression was not affected after treatment with low dose and high dose of G2013. In conclusion our data showed that G2013 can regulate TLR4 signaling pathway during inflammation by reducing downstream signaling molecules, IRAK1 and TRAF6 without altering miR-146a expression.
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Ácidos Hexurônicos/farmacologia , Quinases Associadas a Receptores de Interleucina-1/metabolismo , MicroRNAs/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator 6 Associado a Receptor de TNF/metabolismo , Receptor 4 Toll-Like/metabolismo , Ácidos Urônicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Quinases Associadas a Receptores de Interleucina-1/genética , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , MicroRNAs/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator 6 Associado a Receptor de TNF/genética , Fatores de Tempo , Receptor 4 Toll-Like/genéticaRESUMO
A protective response against tetanus toxin and toxoid demands efficient specific T cell and B cell responses. Tetanus neurotoxin (TeNT), a 150 kDa polypeptide, is the main cause of tetanus disease. TeNT consists of two structurally distinct chains, a 50 kDa N-terminal light (L) and a 100 kDa C-terminal heavy (H) chain. C-terminal heavy (H) chain (fragment C) has two sub-domains named as proximal HCN and carboxy sub-domain or HCC. Beside neural binding property, HCC has been recently found as an immunodominant module of TeNT. In the present study, we investigated the effects of recombinant HCC (rHCC) on the expression of lineage specific transcription factors and secretion of a panel of functional cytokines including IFN-γ, IL-4, and IL-17 from purified human T cells. Our results revealed that T-bet transcript level, as TH1 specific transcription factor, was significantly increased in the cells treated with 10 and 20 µg/ml of rHCC following 48 h treatment(p<0.05). Treated purified human T cells with rHCC showed significant increase in IFN-γ mRNA level and cytokine secretion, but not IL-4 and IL-17, following 48 h treatment. In conclusion, our results showed that treatment of T cells with r HCC resulted in development of Th1 lineage phenotype, which might lead to a specific and protective antibody mediated response against tetanus toxin.
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Clostridium tetani/imunologia , Interferon gama/imunologia , Interleucina-17/imunologia , Metaloendopeptidases/imunologia , Linfócitos T/microbiologia , Toxina Tetânica/imunologia , Tétano/imunologia , Adulto , Humanos , Interferon gama/genética , Interleucina-4/imunologia , RNA Mensageiro/genética , Proteínas Recombinantes/imunologia , Proteínas com Domínio T/genética , Linfócitos T/imunologia , Linfócitos T/metabolismo , Tétano/genética , Tétano/microbiologia , Ativação TranscricionalRESUMO
Breast cancer is the most common cancer and one of the main causes of cancer-related death in the world and has become a major public health concern. Many genes have been shown to be involved in the progress of the breast cancer. Human apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional protein that has an important role in the base excision repair (BER) pathway. The aim of this study was to evaluate the association between ApE1 -656T>G and 1349T>G polymorphisms and the susceptibility to breast cancer in northern Iran population. Samples were obtained from 150 patients diagnosed with breast cancer and 150 control subjects and genotyped by tetra - primer amplification refractory mutation system PCR (T-ARMS-PCR). We observed a significant difference in genotype distributions of -656T>G polymorphism between patients and controls (P= 0.03). Findings indicated that individuals with the variant TG genotypes had a significant decreased risk of breast cancer (OR= 0.55, 95% CI= 0.33 - 0.91, P= 0.019). However, the significant association between 1349T>G polymorphism and breast cancer risk was not observed (P = 0.89). Larger studies are needed to confirm our results.
Assuntos
Neoplasias da Mama/genética , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Humanos , Irã (Geográfico) , Pessoa de Meia-IdadeRESUMO
Prostate cancer (PCa) is the most common malignancy in men and the fourth most common cause of death based on cancer all over the world. Many genes has been shown to be involved in the progress of the prostate cancer. Human apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional protein that has an important role in the base excision repair (BER) pathway. The aim of this study was to evaluate the association of ApE1 1349T>G polymorphism and the susceptibility to prostate cancer in northern Iran population. Samples were collected from 100 patients diagnosed with prostate cancer patients and 100 controls subjects and genotyped by PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism). We observed a significant difference in genotype distributions of ApE1 1349T>G polymorphism between patients and controls (P= 0.039). Our findings revealed individuals with the variant TG and GG had a significant increased risk of prostate cancer (GG: OR= 2.50, 95%CI= 1.063-5.874, P= 0.035. TG: OR= 2.40, 95%CI= 1.16-4.95, P= 0.017). Also, more analyses were showed that G allele were associated with increased risk of prostate cancer (OR= 1.493, 95%CI= 1.007-2.21, P= 0.045). The data from this study indicates that the ApE1 1349T>G polymorphism is associated with increased risk of prostate cancer. Although more studies should be considered with larger number of patients and control subjects to confirm our results.
Assuntos
DNA Liase (Sítios Apurínicos ou Apirimidínicos)/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/genética , Estudos de Casos e Controles , Estudos de Associação Genética , Genótipo , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
Infertility is a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months of regular unprotected sexual intercourse. Both environmental and genetic factors are involved in female infertility. Paraoxonase (PON) is an oxidant enzyme which plays an important role in various diseases and is associated with inflammation, oxidative stress and lipid metabolism. The present study was aimed to evaluate the PON1 192 Q/R gene polymorphism in female infertility. Samples were obtained from 150 patients diagnosed with female infertility and 150 controls subjects and genotyped by Polymerase Chain Reaction—Restriction Fragment Length Polymorphism (PCR—RFLP). The PON genotype frequencies amongst the 70 cases were C/C=40%, C/T=52.8% and T/T=7.2%; the C and T allele frequencies were 66% and 34%, respectively. The PON genotype frequencies amongst the 73 controls were C/C=45.20%, C/T=50.70% and T/T=4.1%; the C and T allele frequencies were 70% and 30%, respectively. We observed a significant difference in the genotype distributions of PON1 192 Q/R polymorphism between patients and controls (P= 0.03). Our findings revealed that individuals with the variant QR had a significant decrease risk of female infertility (OR= 0.55, 95% CI= 0.33 - 0.91, P= 0.019). The data from this study indicates that the PON1 192 Q/R polymorphism may be associated with decreased risk of female infertility. Although more studies should be considered with larger number of patients and control subjects to confirm our results.
Assuntos
Arildialquilfosfatase/genética , Predisposição Genética para Doença , Infertilidade Feminina/genética , Adulto , Feminino , Frequência do Gene/genética , Estudos de Associação Genética , Humanos , Estresse Oxidativo/genética , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único/genética , Gravidez , Espécies Reativas de Oxigênio/metabolismo , RiscoRESUMO
One of the most challenging aspects of colon cancer therapy is rapid acquisition of multidrug resistant phenotype. The multidrug resistance gene 1 (MDR1) product, p—glycoprotein (P—gp), pump out a variety of anticancer agents from the cell, giving rise to a general drug resistance against chemotherapeutic agents. The aim of this study was to investigate the effect of a specific MDR1 small interference RNA (siRNA) on sensitivity of oxaliplatin—resistant SW480 human colon cancer cell line (SW480/OxR) to the chemotherapeutic drug oxaliplatin. SW480 cells were made resistant by continuous incubation with stepwise serially increased concentrations of oxaliplatin over a 6—months period. Resistance cell were subsequently transfected with specific MDR1 siRNA. Relative MDR1 mRNA expression was measured by Quantitative real—time PCR. Western blot analysis was performed to determine the protein levels of P—gp. The cytotoxic effects of oxaliplatin and MDR1 siRNA, alone and in combination were assessed using MTT and the number of apoptotic cells was determined with the TUNEL assay. MDR1 siRNA effectively reduced MDR1 expression in both mRNA and protein levels. MDR1 down—regulation synergistically increased the cytotoxic effects of oxaliplatin and spontaneous apoptosis SW480/OxR. Our data demonstrates that RNA interference could down regulate MDR1 gene expression and reduce the P—gp level, and partially reverse the drug resistance in SW480/OxR cells in vitro. Therefore, the results could suggest that MDR1 silencing may be a potent adjuvant in human colon chemotherapy.