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Aim: This study was conducted to investigate the effect of fibrin glue-CM11 antibacterial peptide mixture (FG-P) on the healing of infected wounds in vivo. Materials & methods: We formulated a mixture of FG-P and evaluated its antimicrobial activity in vitro against multidrug-resistant (MDR) bacteria involved in wound infection as well as its healing effect on wound infected by methicillin-resistant S. aureus (MRSA) in vivo. Results: The peptide had an MIC of 8 µg/ml against all bacteria isolates. Growth inhibition zones were evident for FG-P compared with FG. The in vivo study showed that the FG-P could be significantly effective in healing the MRSA-infected wound. Conclusion: The use of FG-P mixture is a very suitable option for treating infected wounds.
[Box: see text].
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Stem cells transplantation (SCT) is known as a newfound strategy for multiple sclerosis (MS) treatment. Human umbilical cord mesenchymal stem cells (hUCMSCs) contain various regenerative features. Experimental autoimmune encephalomyelitis (EAE) is a laboratory model of MS. This meta-analysis study was conducted to assess the overall therapeutic effects of hUCMSCs on reduction of clinical score (CS) and restoration of active movement in EAE-induced animals. For comprehensive searching (in various English and Persian databases until May 1, 2024), the main keywords of "Experimental Autoimmune Encephalomyelitis", "Multiple Sclerosis", "Human", "Umbilical Cord", "Mesenchymal", and "Stem Cell" were hired. Collected data were transferred to the citation manager software (EndNote x8) and duplicate papers were merged. Primary and secondary screenings were applied (according to the inclusion and exclusion criteria) and eligible studies were prepared for data collection. CS of two phases of peak and recovery of EAE were extracted as the difference in means and various analyses including heterogeneity, publication bias, funnel plot, and sensitivity index were reported. Meta-analysis was applied by CMA software (v.2), P<0.05 was considered a significant level, and the confidence interval (CI) was determined 95% (95% CI). Six eligible high-quality (approved by ARRIVE checklist) papers were gathered. The difference in means of peak and recovery phases were -0.775 (-1.325 to -0.225; P=0.006; I2=90.417%) and -1.230 (-1.759 to -0.700; P<0.001; I2=93.402%), respectively. The overall therapeutic effects of SCT of hUCMSCs on the EAE cases was -1.011 (95% CI=-1.392 to -0.629; P=0.001). hUCMSCs transplantation through the intravenous route to the animal MS model (EAE) seems a considerably effective procedure for the alleviation of motor defects in both phases of peak and recovery.
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Infectious diseases are among the factors that account for a significant proportion of disease-related deaths worldwide. The primary treatment approach to combat microbial infections is the use of antibiotics. However, the widespread use of these drugs over the past two decades has led to the emergence of resistant microbial species, making the control of microbial infections a serious challenge. One of the most important solutions in the field of combating infectious diseases is the regulation of the host's defense system. Toll-like receptors (TLRs) play a crucial role in the first primary defense against pathogens by identifying harmful endogenous molecules released from dying cells and damaged tissues as well as invading microbial agents. Therefore, they play an important role in communicating and regulating innate and adaptive immunity. Of course, excessive activation of TLRs can lead to disruption of immune homeostasis and increase the risk of inflammatory reactions. Targeting TLR signaling pathways has emerged as a new therapeutic approach for infectious diseases based on host-directed therapy (HDT). In recent years, stem cell-derived exosomes have received significant attention as factors regulating the immune system. The regulation effects of exosomes on the immune system are based on the HDT strategy, which is due to their cargoes. In general, the mechanism of action of stem cell-derived exosomes in HDT is by regulating and modulating immunity, promoting tissue regeneration, and reducing host toxicity. One of their most important cargoes is microRNAs, which have been shown to play a significant role in regulating immunity through TLRs. This review investigates the therapeutic properties of stem cell-derived exosomes in combating infections through the interaction between exosomal microRNAs and Toll-like receptors.
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Exossomos , MicroRNAs , Células-Tronco , Receptores Toll-Like , Exossomos/metabolismo , Receptores Toll-Like/metabolismo , Humanos , MicroRNAs/metabolismo , MicroRNAs/genética , Animais , Células-Tronco/metabolismo , Transdução de Sinais , Imunidade Inata , Doenças Transmissíveis/imunologia , Doenças Transmissíveis/metabolismo , Imunidade AdaptativaRESUMO
The present study aimed to investigate the neuroprotective activity of the black peel pomegranate extract, and silver nanoparticles (AgNPs) biosynthesized using the extract. We pretreated the human neuroblastoma SH-SY5 cells with the extract and AgNPs and evaluated the neuroprotective activity of these agents against methamphetamine (Meth) cytotoxicity. The NPs were spherical with 19 ± 8 nm size, - 28 mV surface charge, and 0.20 PDI. Meth killed the cells by increasing proapoptotic (Bax, PTEN, AKT, PI3K, NF-κB, P53, TNF-α, Cyt C, and Cas 3) and decreasing the antiapoptotic genes (Bcl-2) expression. Exposure to Meth caused DNA fragmentation and increased the intercellular ROS and malondialdehyde (MDA) levels while reducing the mitochondrial membrane potential (MMP). A 4-h pretreatment of the cells with the extract and AgNPs could retain the viability of the cells above 80% by increasing the Bcl-2 expression up to fourfold and inhibiting the cell death pathways. ROS, MDA, and MMP levels in the pretreated cells were close to the control group. The percentage of necrosis in cells pretreated with the extract and AgNPs declined to 32% and 8%, respectively. Our promising findings indicated that AgNPs could reduce Meth-induced oxidative stress and prevent necrotic and apoptotic cell death by regulating related genes' expression.
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Nanopartículas Metálicas , Metanfetamina , Neuroblastoma , Humanos , Prata/farmacologia , Espécies Reativas de Oxigênio , Morte Celular , Necrose , Metanfetamina/toxicidadeRESUMO
BACKGROUND: The creation of brand-new, potent, and less harmful medications to treat leukemia is urgently needed. Antimicrobial peptides (AMPs) have drawn a lot of interest as potential substitutes for chemotherapy. OBJECTIVE: In the present investigation, the anticancer activity of CM11, a short cationic AMP, was assessed on Jurkat and Raji leukemia cell lines and peripheral blood mononuclear cells (PBMCs). METHODS: Different CM11 doses were applied to the Jurkat and Raji cell lines and PBMCs throughout a 24-hour period. The impact of the CM11 on cell viability and toxicity was assessed using an MTT assay. Flow cytometry and Real-Time PCR were used to analyze the effect of this peptide on apoptotic/necrosis pathways and assess the ratio expression of the P53 and Bcl-2 genes, respectively. RESULTS: Despite the fact that peptide toxicity was successful in a variety of cell lines, cancer cells were more sensitive to the medication. The survival of Jurkat and Raji cell lines treated with 32 µg/ml peptide was 47% and 51%, respectively, while the survival of normal PBMC cells was about 65%. According to flow cytometry, Jurkat and Raji cells exposed to peptide had much greater levels of apoptosis than PBMCs. Peptide-treated cells were associated with increased expression of P53 the gene and decreased expression of the Bcl-2 gene. CONCLUSION: These results revealed that the CM11 caused more cytotoxicity to leukemia Raji and Jurkat leukemia cells compared to the normal cells by apoptosis pathway. Our findings demonstrated the potential of CM11 peptide to develop as a new antileukemic agent.
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Cecropinas , Leucemia , Humanos , Cecropinas/farmacologia , Meliteno/farmacologia , Leucócitos Mononucleares , Proteína Supressora de Tumor p53/genética , Apoptose , Células Jurkat , Peptídeos/farmacologia , Leucemia/tratamento farmacológico , Linhagem Celular TumoralRESUMO
Dental caries and oral infections have become a widespread issue in the modern world. This study aimed to investigate the antibacterial, antifungal, and cytotoxicity characteristics of the extracts of Echinacea purpura, Arctium lappa, and the essential oil of Zataria multiflora as a potential herbal mouthwash. The essential oil of Z. multiflora leaves and the extracts of E. purpurea and A. lappa roots were prepared. The characterization was carried out by GC-MS and also, total phenol and flavonoid were assed for all three samples. The antimicrobial and anti-biofilm effects were evaluated against Streptococcus mutans, Streptococcus mitis, Streptococcus salivarius, Lactobacillus acidophilus, Escherichia coli, Staphylococcus aureus, and Candida albicans. The cytotoxic effect of the samples was evaluated on HEK 293 and HDFa cells by MTT test. Thymol and carvacrol contents in EO of Z. multiflora were measured at 31% and 42.2%, respectively. A. lappa had the lowest total phenolic and flavonoid value among the samples. On the other hand, the total phenolic content of Z. multiflora and the total flavonoid content of E. purpurea were the highest. The MIC values of Zataria, Arctium, and Echinacea against S. mutans were 0.011% v/v, 187.5 mg/ml, and 93.75 mg/ml, while MBC were 0.011% v/v, 375 mg/ml, and 187.5 mg/ml, respectively. The formulation showed bactericidal activity against S. mutans in the concentration of 5.86 mg/ml for Echinacea and Burdock extracts and 0.08 µl/ml for EO of Zataria. The formulation significantly affected microbial biofilm formation and induced biofilm degradation. The cell viability percentages were higher than 50% during 24 and 48 h. The formulation had a significant antimicrobial effect on cariogenic bacteria and C. albicans, with the lowest cytotoxic effects. Therefore, this formulation can be an appropriate candidate for mouthwash.
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Cornea as the outermost layer of the eye is at risk of various genetic and environmental diseases that can damage the cornea and impair vision. Corneal transplantation is among the most applicable surgical procedures for repairing the defected tissue. However, the scarcity of healthy tissue donations as well as transplantation failure has remained as the biggest challenges in confront of corneal grafting. Therefore, alternative approaches based on stem-cell transplantation and classic regenerative medicine have been developed for corneal regeneration. In this review, the application and limitation of the recently-used advanced approaches for regeneration of cornea are discussed. Additionally, other emerging powerful techniques such as 5D printing as a new branch of scaffold-based technologies for construction of tissues other than the cornea are highlighted and suggested as alternatives for corneal reconstruction. The introduced novel techniques may have great potential for clinical applications in corneal repair including disease modeling, 3D pattern scheming, and personalized medicine.
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Bioimpressão , Engenharia Tecidual , Córnea , Impressão Tridimensional , Regeneração , Medicina Regenerativa , Engenharia Tecidual/métodos , Alicerces TeciduaisRESUMO
It has been about a century since the discovery of the first antibiotic, and during this period, several antibiotics were produced and marketed. The production of high-potency antibiotics against infections led to victories, but these victories were temporary. Overuse and misuse of antibiotics have continued to the point that humanity today is almost helpless in the fight against infection. Researchers have predicted that by the middle of the new century, there will be a dark period after the production of antibiotics that doctors will encounter antibiotic-resistant infections for which there is no cure. Accordingly, researchers are looking for new materials with antimicrobial properties that will strengthen their ammunition to fight antibiotic-resistant infections. One of the most important alternatives to antibiotics introduced in the last three decades is antimicrobial peptides (AMPs), which affect a wide range of microbes. Due to their different antimicrobial properties from antibiotics, AMPs can fight and kill MDR, XDR, and colistin-resistant bacteria through a variety of mechanisms. Therefore, in this study, we intend to use the latest studies to give a complete description of AMPs, the importance of colistin-resistant bacteria, and their resistance mechanisms, and represent impact of AMPs on colistin-resistant bacteria. KEY POINTS: ⢠AMPs as limited options to kill colistin-resistant bacteria. ⢠Challenge of antibiotics resistance, colistin resistance, and mechanisms. ⢠What is AMPs in the war with colistin-resistant bacteria?
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Anti-Infecciosos , Colistina , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos , Bactérias , Colistina/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Multimicrobial infections caused by pathobionts are called dysbiotic multimicrobial illnesses. Commercial mouthwashes, such as chlorhexidine, have negative side effects that can prevent tooth decay and infection. The present study aimed to determine the antifungal, antibacterial, and cytotoxicity characteristics of the propolis extracts from different areas (Iran). The ethanolic extract of propolis was prepared. GC/MS carried out the characterization to determine the thymol, carvacrol, and menthol extracts, and also, total phenol and flavonoid were assed for all samples. The antimicrobial and antibiofilm effects were evaluated against S. mutans, S. mitis, S. salivarius, L. acidophilus, E. coli, S. aureus, and C. albicans. The cytotoxic effect of extracts was measured on human fibroblast cells by MTT test. The MIC values in mg mL-1 were ranged as follows: S. salivarius (0.003 to 0.048), S. mutans (0.003 to 0.029), S. mitis (0.007 to 0.058), L. acidophilus (0.007 to 0.117), C. albicans (0.014 to 0.234), E. coli (0.007 to 0.058), and S. aureus (0.007 to 0.058), while MBC were, respectively, S. mutans (0.007 to 0.058), S. salivarius (0.007 to 0.117), S. mitis (0.007 to 0.117), L. acidophilus (0.014 to 0.234), C. albicans (0.029 to 0.468), E. coli (0.014 to 0.234), and S. aureus (0.007 to 0.117). Cariogenic bacteria and Candida albicans were demonstrated to be resistant to propolis extracts. Therefore, propolis extracts may make good mouthwashes.
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Própole , Antibacterianos/farmacologia , Candida albicans , Escherichia coli , Fibroblastos , Humanos , Irã (Geográfico) , Lactobacillus acidophilus , Testes de Sensibilidade Microbiana , Antissépticos Bucais/farmacologia , Extratos Vegetais/farmacologia , Própole/química , Própole/farmacologia , Staphylococcus aureusRESUMO
Cancer is one of the leading causes of mortality worldwide. Although chemotherapeutic agents have been effectively designed to increase the survival rates of some patients, the designed chemotherapeutic agents necessarily deliver toxic chemotherapeutic drugs to healthy tissues, resulting in serious side effects. Cancer cells can often acquire drug resistance after repeatedly administering current chemotherapeutic agents, restricting their efficacy. Given such obstacles, investigators have attempted to distribute chemotherapeutic agents using targeted drug delivery systems (DDSs), especially nanotechnology-based DDSs. The lipid-based nanoparticles (LBNPs) are a large and complex class of substances utilized to manage various diseases, especially cancers. Liposomes seem to be the most frequently employed LBNPs, owing to their high biocompatibility, bioactivity, stability, and flexibility. Solid lipid NPs and non-structured lipid carriers have lately received a lot of interest. In addition, several reports focused on novel therapies via LBNPs to manage various forms of cancer. In the present research, the latest improvements in applying LBNPs have been shown to deliver different therapeutic agents to cancerous cells and be a quite successful candidate in cancer therapy.
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Antineoplásicos , Nanopartículas , Neoplasias , Portadores de Fármacos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Humanos , Lipídeos , Lipossomos , Neoplasias/tratamento farmacológicoRESUMO
BACKGROUND: Dental caries is known as a multimicrobial disease. Caries are very prevalent in numerous countries, and the incidence is higher in underdeveloped countries than in developed countries. Dental caries is a major public health problem, and it is the most prevalent health problem across the world, affecting 2.4 billion people. Natural mouthwashes can be beneficial in the prevention of dental caries and oral infections without the side effects of synthetic mouthwashes. AIM: The aim of the present study was to investigate the antibacterial, antifungal, and cytotoxicity properties of sea salt from different areas of Iran. METHODS AND MATERIALS: Sea salts from different areas (Urmia, Qom, and Jarquyeh) of Iran were collected. In order to define the elemental and mineralogical features of different salt samples, X-ray powder diffraction (XRD) was employed. Different concentrations (0.19-50 mg/mL) of sea salt were used in the antimicrobial and antibiofilm tests. The antimicrobial (MIC, MBC, MFC, and DAD tests) and antibiofilm (formation and degradation tests) effects were evaluated against L. acidophilus, S. aureus, E. coli, S. mitis, S. mutans, S. salivarius, and C. albicans. The cytotoxic effect of salts was evaluated on human gingival fibroblasts by the MTT test. RESULTS: The range of MIC values in mg ml-1 was as follows: S. salivarius (50), S. mutans (50), S. mitis (50), L. acidophilus (12.5 to >50), C. albicans (50), E. coli (12.5 to 25), and S. aureus (12.5 to 25), while MBC values were, S. mutans (>50), S. salivarius (>50), S. mitis (>50), L. acidophilus (50 to >50), C. albicans (>50), E. coli (50), and S. aureus (50). MTT results showed that more than 50% of cell viability depends on decreasing the salt concentration (<1.56 mg/ml). CONCLUSION: Sea salts had significant antimicrobial effects on cariogenic bacteria and C. albicans. Therefore, sea salts can be a suitable candidate for mouthwash.
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Due to the broad-spectrum of antibiotic resistance, herein we investigated the possibility of using imipenemconjugated silver nanoparticles (IMP-AgNPs) against multidrug-resistant isolates of Pseudomonas aeruginosa. For this purpose, 200 clinical isolates were tested against different antibiotics to determine the antimicrobial susceptibility. To identify blaVIM and blaIMP resistance genes, PCR was used. The synthesized AgNPs and conjugants were characterized using UV-vis spectroscopy, XRD, SEM, TEM, DLS, and FTIR. The stability, drug release kinetics, cytotoxicity, hemolytic and apoptotic effects of NPs were also investigated. MIC of the imipenem, AgNPs, and conjugants were evaluated versus P. aeruginosa isolates. Finally, the effects of the IMP-AgNPs to heal burn wounds in rats was evaluated. According to the results, about 68% of isolates showed resistance to imipenem (MIC ≥ 64 µg/ml to ≥ 512 µg/ml). Analytical results verified the synthesis of AgNPs and IMP-AgNPs. A Dose-dependent decrease happened in terms of the MIC values of IMP-AgNPs were also affected by the existence of resistant genes. Low cytotoxic was observed regarding AgNPs which lead to apoptosis. The histopathological results showed a considerable epithelization in treated groups with IMPAgNPs. Accordingly, IMP-AgNPs can be considered as a powerful antibacterial agent to treat the infections caused by multidrug-resistant P. aeruginosa.
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Antibacterianos/administração & dosagem , Farmacorresistência Bacteriana Múltipla , Imipenem/administração & dosagem , Pseudomonas aeruginosa , Prata/administração & dosagem , Nanopartículas Metálicas , Testes de Sensibilidade MicrobianaRESUMO
Many factors including growth factors (GF), scaffold materials, and chemical and physical cues determine the cell behaviors. For many years, growth factors have been considered as the pivotal cell behavior regulators, whereas recent studies emphasize also the key role of physical factors such as mechanical forces, cell shape, surface topographies, and extracellular matrix (ECM) in regulating the cell proliferation, apoptosis, differentiation, etc. through mechanotransduction pathways. In this process, the cell morphology and mechanical properties of the cell's micro/ nano-environments and ECM can be conveyed to the nucleus by regulating transcriptional factors such as Yes-associated protein and transcriptional coactivator with PDZ-binding motif (TAZ). Generally, YAP/TAZ activity is considered as the key factor for the growth of whole organs, however, recent studies have also repeatedly addressed the role of YAP/TAZ in mechanotransduction. In this review, the biological functions of the YAP/TAZ pathway and its contribution to the mechanotransduction and cell behavior regulation in response to the mechanical cues have been summarized. Also, the role of key mechanical checkpoints in the cell including focal adhesions, cytoskeletal tension, Rho small GTPases, and nuclear membrane protein elements involved in the transfer of environmental mechanical cues from the cell surface to the nucleus and their effect in regulating the YAP/TAZ activity are discussed.
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Proteínas de Ciclo Celular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Mecanotransdução Celular , Fatores de Transcrição/metabolismo , Forma Celular/fisiologia , Humanos , Proteínas com Motivo de Ligação a PDZ com Coativador TranscricionalRESUMO
Toxoplasmosis is one of the most important zoonotic diseases with serious health risks for humans, especially for immunodeficient patients, and can lead to abortion in pregnant women worldwide. The oral uptake of sporulated oocysts and/or consumption of undercooked/raw meat of animals infected with Toxoplasma gondii can infect other animals and humans. Heart, liver, and meat tissues of 150 sheep and 150 goats from a slaughterhouse in Ahvaz, Iran, were collected during autumn 2018 and analyzed via polymerase chain reaction (PCR) to detect parasitic DNA in the animal tissues. Moreover, antibodies against T. gondii of 150 sera samples were detected as the targets by in-house enzyme-linked immunosorbent assay (in-house ELISA). A total of 26 (17.3%), 33 (22%), and 48 (32%) of liver, meat, and heart samples in sheep, and a total of 24 (16%), 26 (17.3%), and 36 (24%) of liver, meat, and heart samples in goats, respectively, showed positive PCR results. Besides, the ELISA evaluation of sera samples from 150 sheep and 150 goats resulted in 26 (13.3%) and 16 (10.6%) positive cases, respectively. A significant difference was also found between PCR-positive heart samples and ELISA-positive sera samples of both animal species (p < 0.05), but no significant difference existed between PCR-positive liver samples and ELISA-positive sera samples of both species (p > 0.05). The results of this study confirm the presence of T. gondii in sheep and goats' consumable organs, highlighting the need to avoid consuming raw or uncooked organs of these animal species to prevent human infection with T. gondii.
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AIM: To describe the epidemiological and clinical characteristics along with outcomes of hospitalized Coronavirus Disease 2019 (COVID-19) patients with and without diabetes. METHODS: This retrospective, single-center study included 595 consecutive hospitalized patients with confirmed COVID-19 at Baqiyatallah Hospital in Tehran, Iran, from February 26, 2020 to March 26, 2020. Demographic data, clinical, laboratory, and radiological findings were collected and compared between patients based on diabetes status. Complications and clinical outcomes were followed up until April 4, 2020. RESULTS: From among the 595 hospitalized patients with COVID-19, the median age was 55 years and 401 (67.4%) were male. The most common symptoms included fever (419 [70.4%]), dry cough (368 [61.8%]) and dyspnea (363 [61%]). A total of 148 patients (24.9%) had diabetes, and compared with patients without diabetes, these patients had more comorbidities (eg, hypertension [48.6% vs. 22.3%; P < 0.001]); had higher levels of white blood cell count, neutrophil count, C-reactive protein, erythrocyte sedimentation rate and blood urea nitrogen, and had a higher proportion of patchy ground-glass opacity in chest computed tomography findings (52.7% vs. 25.7%; P < 0.001). Significantly, patients with diabetes had more complications and needed more respiratory support than those without diabetes (P < 0.001). At the end of the follow-up, treatment failure and death was significantly higher in patients with diabetes compared to those without diabetes (17.8% vs. 8.7%; P = 0.003). CONCLUSION: COVID-19 patients with diabetes are at a higher risk of complications and a higher in-hospital mortality during hospitalization. Diabetes status of COVID-19 patients and frequent monitoring of glycemia would be helpful to prevent deteriorating clinical conditions.
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COVID-19/complicações , Diabetes Mellitus/patologia , Mortalidade Hospitalar/tendências , Hospitalização/estatística & dados numéricos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/transmissão , COVID-19/virologia , Comorbidade , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/virologia , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
In recent decades, many novel methods by using nanoparticles (NPs) have been investigated for diagnosis, drug delivery and treatment of cancer. Accordingly, the potential of NPs as carriers is very significant for the delivery of anticancer drugs, because cancer treatment with NPs has led to the improvement of some of the drug delivery limitations such as low blood circulation time and bioavailability, lack of water solubility, drug adverse effect. In addition, the NPs protect drugs against enzymatic degradation and can lead to the targeted and/or controlled release of the drug. The present review focuses on the potential of NPs that can help the targeted and/or controlled delivery of anticancer agents for cancer therapy.
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Antineoplásicos/química , Portadores de Fármacos/química , Nanopartículas/química , Polímeros/química , Antineoplásicos/metabolismo , Antineoplásicos/uso terapêutico , Materiais Biocompatíveis/química , Liberação Controlada de Fármacos , Humanos , Neoplasias/tratamento farmacológicoRESUMO
An ultrahigh sensitive, simple and reliable Electrochemiluminescence (ECL) immunosensor for selective quantification of p53 protein was designed according to the enhancement effects of AuNPs on ECL emission of CdS nanocrystals (CdS NCs). CdS NCs were immobilized on the glassy carbon electrode and AuNPs introduced to the process through formation of a sandwich-type immunocomplex between first anti-p53/p53/ secondary anti-p53. ECL of CdS NCs firstly evoked the SPR of AuNPs which in return amplified the CdS NCs ECL intensity. By using graphene oxide in immunosensor fabrication procedure, and attaching more AuNPs on the surface of the electrode, the ECL intensity was further increased resulting in much higher sensitivity. After applying the optimum conditions, the linear range of the developed immunosensor was found between 20 and 1000â¯fg/ml with a calculated limit of detection of 4â¯fg/ml. Moreover, the interference, reproducibility and storage stability studies of the immunosensor were investigated. Finally, immunosensor's authenticity was evaluated by detecting the p53 protein in human spikes which offers it as a potential in early detection of cancer, monitoring the cancer progress and clinical prognosis.
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Anticorpos Imobilizados/química , Técnicas Biossensoriais/instrumentação , Compostos de Cádmio/química , Ouro/química , Grafite/química , Nanopartículas/química , Sulfetos/química , Proteína Supressora de Tumor p53/sangue , Biomarcadores Tumorais/sangue , Técnicas Eletroquímicas/instrumentação , Desenho de Equipamento , Humanos , Imunoensaio/instrumentação , Limite de Detecção , Nanopartículas Metálicas/química , Neoplasias/sangueRESUMO
The respiratory system is a complex group of organs in the human body, all of which are necessary in breathing. Due to its special anatomy and composition, after exposure to various damaging factors such as micro particles, carbon granules and toxic gases, the respiratory system can be affected by a variety of damage without return to its original state. Currently, the prevalence of lung diseases, including asthma, and chronic obstructive pulmonary diseases, such as emphysema, has increased remarkably. New therapeutic approaches are desperately needed to discover regenerative medicine approaches, especially cell therapy. This review summarizes the recent advances in stem cell treatments and the research efforts conducted through the application of stem cell therapy for respiratory system diseases. In particular, researchers have used animal models to gather data about treating lung injury by stem cell transplantation. This review concentrated on the findings about route, timing and adjustment of cell transplantation dose, optimum stem cell type selection and potency marker of cells as therapeutic agents. These factors are essential subjects for approval and clinical transplantation. The current clinical trials aiming at treatment of lung diseases by stem cells are mentioned and discussed.
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Pneumopatias/terapia , Pulmão/citologia , Pulmão/fisiologia , Regeneração , Transplante de Células-Tronco/métodos , Animais , Bioengenharia/métodos , Ensaios Clínicos como Assunto , Humanos , Pulmão/patologia , Pneumopatias/patologia , Células-Tronco/citologiaRESUMO
Owing to essential role in bacterial survival, DNA gyrase has been exploited as a validated drug target. However, rapidly emerging resistance to gyrase-targeted drugs such as widely utilized fluoroquinolones reveals the necessity to develop novel compounds with new mechanism of actions against this enzyme. Here, an attempt has been made to identify new drug-like molecules for Shigella flexneri DNA gyrase inhibition through in silico approaches. The structural similarity search was carried out using the natural product simocyclinone D8, a unique gyrase inhibitor, to virtually screen ZINC database. A total of 11830 retrieved hits were further screened for selection of high-affinity compounds by implementing molecular docking followed by investigation of druggability according to Lipinski's rule, biological activity and physiochemical properties. Among the hits initially identified, three molecules were then confirmed to have reasonable gyrase-binding affinity and to follow Lipinski's rule. Based on these in silico findings, three compounds with different chemical structures from previously identified gyrase inhibitors were proposed as potential candidates for the treatment of fluoroquinolone-resistant strains and deserve further investigations.