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1.
Environ Geochem Health ; 45(11): 7759-7773, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37428427

RESUMO

Zahedan City is situated in the Sistan basin, a highly active dust source region that poses significant risks to human and ecological health due to potentially toxic elements (PTEs) present in atmospheric dust. In this study, we investigated the concentration, sources, and human health risk assessment of PTEs in 88 monthly atmospheric dust samples collected between December 2020 and October 2021 using inductively coupled plasma mass spectrometry. The results showed that the concentrations of PTEs in atmospheric dust followed the descending order of Mn > Zn > Ba > Sr > Cr > V > Ni > Cu > Pb > Co > As > Mo > Cd. The calculated enrichment factors revealed significant enrichment for As > Zn, moderate enrichment Pb > Ni, deficiency to minimal enrichment for Cr > Mn > Fe > Sr > Cd > V > Cu > Ba > Co, and no enrichment for Mo. Arsenic was found to be the major contributor to the potential ecological risk index, accounting for 55% of the total risk. The widespread utilization of arsenic-based pesticides in the surrounding agricultural lands may be a significant contributor to the severe arsenic pollution in the region. The winter season exhibited the highest monthly mean concentrations of Zn and Pb possibly due to temperature inversions trapping local anthropogenic pollutants near the Earth's surface. Cluster analysis revealed a strong correlation between Ni-Cr-Fe-V-Mn-Al, which shows mainly the geogenic source for these elements. The predominant exposure route for non-carcinogenic risk to humans was ingestion. The hazard index (HI) values for the heavy metals studied decreased in the following order: Cr > As > Pb > Ni > Zn > Cu > Cd, for both children and adults. The HI values indicated that there was no possible non-carcinogenic risk associated with exposure to these heavy metals in Zahedan's atmospheric dust. The result of the inhalation cancer risk assessment suggested that while the potential risks of cancer for As, Cd, Cr, and Ni were below the safe level, the levels of Chromium were close enough to the threshold to warrant further investigation and monitoring.


Assuntos
Arsênio , Metais Pesados , Neoplasias , Adulto , Criança , Humanos , Poeira/análise , Monitoramento Ambiental , Arsênio/análise , Irã (Geográfico) , Cádmio/análise , Chumbo/análise , Metais Pesados/análise , Medição de Risco , China
2.
Water Sci Technol ; 83(11): 2732-2743, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34115627

RESUMO

A novel photocatalytic continuous system has been proposed for the treatment of tannery waste water, which has high levels of environmental pollutants. The purification process was performed by passing wastewater on a titanium dioxide (TiO2)-coated surface, which is continuously activated by irradiation of ultraviolet light. To improve the yield of the process, ferric chloride (FeCl3) was used as a coagulation agent. The organic and inorganic compounds, as well as the microorganisms in the tannery wastewater media, were degraded through a photocatalytic process. The results revealed that total dissolved solids and total suspended solids contents were significantly decreased from 8,450 and 8,990 mg·L-1 to 4,032 and 4,127 mg·L-1, respectively. Furthermore, the chemical oxygen demand content of the sample was reduced from 370 to 50 mg·L-1 after the addition of 100 mL of FeCl3 and 4 h of treatment. The same results were observed for the elimination of sulfate and chromium ions, which led to a decline in electrical conductivity. This suggests that introducing 100 mL of FeCl3 as the coagulation agent and continuous treatment with photocatalityc set-up could be considered as an effective method for the purification of tannery wastewaters.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Catálise , Titânio , Águas Residuárias , Poluentes Químicos da Água/análise
3.
Nat Mater ; 18(10): 1124-1132, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31133730

RESUMO

Ex vivo CRISPR gene editing in haematopoietic stem and progenitor cells has opened potential treatment modalities for numerous diseases. The current process uses electroporation, sometimes followed by virus transduction. While this complex manipulation has resulted in high levels of gene editing at some genetic loci, cellular toxicity was observed. We have developed a CRISPR nanoformulation based on colloidal gold nanoparticles with a unique loading design capable of cellular entry without the need for electroporation or viruses. This highly monodispersed nanoformulation avoids lysosomal entrapment and localizes to the nucleus in primary human blood progenitors without toxicity. Nanoformulation-mediated gene editing is efficient and sustained with different CRISPR nucleases at multiple loci of therapeutic interest. The engraftment kinetics of nanoformulation-treated primary cells in humanized mice are better relative to those of non-treated cells, with no differences in differentiation. Here we demonstrate non-toxic delivery of the entire CRISPR payload into primary human blood progenitors.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Nanopartículas Metálicas/química , Células-Tronco/citologia , Animais , Sangue , Eletroporação , Ouro/química , Humanos
4.
Int J Toxicol ; 39(4): 328-340, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483993

RESUMO

Gold nanoparticles (AuNPs) have been widely used in many biological and biomedical applications. In this regard, their surface modification is of paramount importance in order to increase their cellular uptake, delivery capability, and optimize their distribution inside the body. The aim of this study was to examine the effects of AuNPs on cytotoxicity, oxidant/antioxidant parameters, and DNA damage in HepG2 cells and investigate the potential toxic effects of different surface modifications such as polyethylene glycol (PEG) and polyethyleneimine (PEI; molecular weights of 2,000 (low molecular weight [LMW]) and 25,000 (high molecular weight [HMW]). The study groups were determined as AuNPs, PEG-coated AuNPs (AuNPs/PEG), low-molecular weight polyethyleneimine-coated gold nanoparticles (AuNPs/PEI LMW), and high-molecular weight polyethyleneimine-coated gold nanoparticles (AuNPs/PEI HMW). After incubating HepG2 cells with different concentrations of nanoparticles for 24 hours, half maximal inhibitory concentrations (the concentration that kills 50% of the cells) were determined as 166.77, 257.73, and 198.44 µg/mL for AuNPs, AuNPs/PEG, and AuNPs/PEI LMW groups, respectively. Later, inhibitory concentration 30 (IC30, the concentration that kills 30% of the cells) doses were calculated, and further experiments were performed on cells that were exposed to IC30 doses. Although intracellular reactive oxygen species levels significantly increased in all nanoparticles, AuNPs as well as AuNPs/PEG did not cause any changes in oxidant/antioxidant parameters. However, AuNPs/PEI HMW particularly induced oxidative stress as evidence of alterations in lipid peroxidation and protein oxidation. These results suggest that at IC30 doses, AuNPs do not affect oxidative stress and DNA damage significantly. Polyethylene glycol coating does not have an impact on toxicity, however PEI coating (particularly HMW) can induce oxidative stress.


Assuntos
Ouro/toxicidade , Nanopartículas Metálicas/toxicidade , Polietilenoglicóis/toxicidade , Polietilenoimina/toxicidade , Catalase/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Ouro/química , Células Hep G2 , Humanos , Nanopartículas Metálicas/química , Estresse Oxidativo/efeitos dos fármacos , Polietilenoglicóis/química , Polietilenoimina/química , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
5.
Mol Cell Probes ; 41: 8-13, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30053513

RESUMO

Staphylococcus aureus is a gram-positive and opportunistic pathogen that is one of the most common causes of nosocomial infections; therefore, its rapid diagnosis is important and valuable. Today, the use of nanoparticles is expanding due to their unique properties. The purpose of the present study is the determination of S. aureus by a colorimetric method based on gold nanoparticles (AuNPs). Firstly, S. aureus was cultured on both LB media (broth and agar) and their chromosomal DNA was extracted. Afterwards, primers and biosensor were designed based on Protein A sequence data in the gene bank. PCR assay was performed under optimal conditions and the PCR product was electrophoresed on 2-percent agarose gel. The synthesized biosensors were conjugated with AuNPs and, eventually, a single-stranded genome was added to the conjugated AuNPs and hybridization was performed. The results were evaluated based on color change detected by the naked eye, optical spectrophotometry, and transient electron microscopy. Finally, the sensitivity and specificity of the AuNP-biosensor were determined. The results of the present study showed a 390 bp band on the agarose electrophoresis gel, which confirmed the presence of Protein A genes on the chromosome of the bacteria. The PCR and colorimetric methods were compared with each other. The sensitivity of the PCR and colorimetric methods were 30 ng µL-1 and 10 ng µL-1, respectively. The limit of detection (LOD) equaling 8.73 ng µL-1 was determined and the specificity of the method was confirmed by the DNA of other bacteria. According to the results, the present method is rapid and sensitive in detecting S. aureus.


Assuntos
Técnicas Biossensoriais/métodos , Ouro/química , Nanopartículas Metálicas/química , Staphylococcus aureus/isolamento & purificação , Difusão Dinâmica da Luz , Limite de Detecção , Nanopartículas Metálicas/ultraestrutura , Tamanho da Partícula , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade , Espectrofotometria Ultravioleta , Staphylococcus aureus/genética
6.
Nanotechnology ; 28(2): 025103, 2017 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-27924783

RESUMO

It is generally known that gold nanoparticles are localised in the cytoplasm and, if synthesised in small sizes or functionalized with specific proteins, they enter the cell nucleus. However, there is no report emphasising the importance of surface functionalization in their accumulation in the nucleolus. Here, for the first time in the literature, it is proposed that functionalization of gold nanoparticles with a thin layer of polyethyleneimine (PEI) spearheads them to the nucleolus of hard-to-transfect post-mitotic dorsal root ganglion neurones in a size-independent manner. As a potential for theranostic applications, it was found that functionalization with a thin layer of PEI affected the emission signal intensity of gold nanoparticles so that the cellular biodistribution of nanoparticles was visualised clearly under both confocal and two-photon microscopes.


Assuntos
Núcleo Celular/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Gânglios Espinais/metabolismo , Ouro , Nanopartículas Metálicas/química , Neurônios/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Células Cultivadas , Gânglios Espinais/citologia , Ouro/química , Ouro/farmacocinética , Ouro/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Neurônios/citologia
7.
J Microencapsul ; 32(7): 687-98, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26471402

RESUMO

Targeted delivery of therapeutics is the favourable idea, whereas it is possible to distribute the therapeutically active drug molecule only to the site of action. For this purpose, in this study, catalase encapsulated poly(D,L-lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles were developed and an endothelial target molecule (anti-ICAM-1) was conjugated to this carrier system in order to decrease the oxidative stress level in the target site. According to the enzymatic activity results, initial catalase activity of nanoparticles was increased from 27.39 U/mg to up to 45.66 U/mg by adding 5 mg/mL bovine serum albumin (BSA). After 4 h, initial catalase activity was preserved up to 46.98% while free catalase retained less than 4% of its activity in proteolytic environment. Furthermore, FITC labelled anti-ICAM-1 targeted catalase encapsulated nanoparticles (anti-ICAM-1/CatNPs) were rapidly taken up by cultured endothelial cells and concomitantly endothelial cells were resistant to H2O2 induced oxidative impairment.


Assuntos
Vasos Sanguíneos/efeitos dos fármacos , Catalase/farmacologia , Molécula 1 de Adesão Intercelular/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Poliésteres/química , Polietilenoglicóis/química , Animais , Antioxidantes/metabolismo , Vasos Sanguíneos/metabolismo , Catalase/administração & dosagem , Células Cultivadas , Cães , Composição de Medicamentos , Células Endoteliais/efeitos dos fármacos , Excipientes , Peróxido de Hidrogênio/farmacologia , L-Lactato Desidrogenase/metabolismo , Malondialdeído/metabolismo , Nanopartículas , Tamanho da Partícula
8.
Int J Pharm ; 655: 124057, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38552752

RESUMO

Cancer remains one of the major causes of death globally, with one out of every six deaths attributed to the disease. The impact of cancer is felt on psychological, physical, and financial levels, affecting individuals, communities, and healthcare institutions. Conventional cancer treatments have many challenges and inadequacies. Nanomedicine, however, presents a promising solution by not only overcoming these problems but also offering the advantage of combined therapy for treatment-resistant cancers. Nanoparticles specifically engineered for use in nanomedicine can be efficiently targeted to cancer cells through a combination of active and passive techniques, leading to superior tumor-specific accumulation, enhanced drug availability, and reduced systemic toxicity. Among various nanoparticle formulations designed for cancer treatment, gold nanoparticles have gained prominence in the field of nanomedicine due to their photothermal, photodynamic, and immunologic effects without the need for photosensitizers or immunotherapeutic agents. To date, there is no comprehensive literature review that focuses on the photothermal, photodynamic, and immunologic effects of gold nanoparticles. In this review, significant attention has been devoted to examining the parameters pertaining to the structure of gold nanoparticles and laser characteristics, which play a crucial role in influencing the efficacy of photothermal therapy (PTT) and photodynamic therapy (PDT). Moreover, this article provides insights into the success of PTT and PDT mediated by gold nanoparticles in primary cancer treatment, as well as the immunological effects of PTT and PDT on metastasis and recurrence, providing a promising strategy for cancer therapy. In summary, gold nanoparticles, with their unique properties, have the potential for clinical application in various cancer therapies, including the treatment of primary cancer, recurrence and metastasis.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Ouro/química , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/química , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/química
9.
Eur J Pharm Biopharm ; 203: 114432, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39097115

RESUMO

Non-melanoma skin cancer (NMSC) is one of the most prevalent cancers, leading to significant mortality rates due to limited treatment options and a lack of effective therapeutics. Janus kinase (JAK1), a non-receptor tyrosine kinase family member, is involved in various cellular processes, including differentiation, cell proliferation and survival, playing a crucial role in cancer progression. This study aims to provide a more effective treatment for NMSC by concurrently silencing the JAK1 gene and administering 5-Fluorouracil (5-FU) using liposome nanocomplexes as delivery vehicles. Utilizing RNA interference (RNAi) technology, liposome nanocomplexes modified with polyethylene imine (PEI) were conjugated with siRNA molecule targeting JAK1 and loaded with 5-FU. The prepared formulations (NL-PEI) were characterized in terms of their physicochemical properties, morphology, encapsulation efficiency, in vitro drug release, and stability. Cell cytotoxicity, cell uptake and knockdown efficiency were evaluated in human-derived non-melanoma epidermoid carcinoma cells (A-431). High contrast transmission electron microscopy (CTEM) images and dynamic light scattering (DLS) measurements revealed that the nanocomplexes formed spherical morphology with uniform sizes ranging from 80-120 nm. The cationic NL-PEI nanocomplexes successfully internalized within the cytoplasm of A-431, delivering siRNA for specific sequence binding and JAK1 gene silencing. The encapsulation of 5-FU in the nanocomplexes was achieved at 0.2 drug/lipid ratio. Post-treatment with NL-PEI for 24, 48 and 72 h showed cell viability above 80 % at concentrations up to 8.5 × 101 µg/mL. Notably, 5-FU delivery via nanoliposome formulations significantly reduced cell viability at 5-FU concentration of 5 µM and above (p < 0.05) after 24 h of incubation. The NL-PEI nanocomplexes effectively silenced the JAK1 gene in vitro, reducing its expression by 50 %. Correspondingly, JAK1 protein level decreased after transfection with JAK1 siRNA-conjugated liposome nanocomplexes, leading to a 37 % reduction in pERK (phosphor extracellular signal-regulated kinase) protein expression. These findings suggest that the combined delivery of JAK1 siRNA and 5-FU via liposomal formulations offers a promising and novel treatment strategy for targeting genes and other identified targets in NMSC therapy.


Assuntos
Sistemas de Liberação de Medicamentos , Fluoruracila , Inativação Gênica , Janus Quinase 1 , Lipossomos , RNA Interferente Pequeno , Neoplasias Cutâneas , Humanos , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Fluoruracila/administração & dosagem , Fluoruracila/farmacologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Linhagem Celular Tumoral , Janus Quinase 1/genética , Janus Quinase 1/metabolismo , Inativação Gênica/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Nanopartículas/química , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Interferência de RNA
10.
Food Sci Nutr ; 11(5): 2243-2253, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37181302

RESUMO

The main purpose of this study was to evaluate the effects of the cushion box and closed let-down ladder usage in minimizing mechanical damage to corn kernels during free fall. Kernels from a single lot of cultivar KSC 705 were evaluated for percentage of breakage using three drop methods (free fall, with cushion box, and with closed let-down ladder) at five different moisture contents (10%, 15%, 20%, 25%, and 30%), and three drop heights (5, 10, and 15 m). The results showed that the drop methods had a significant effect on the breakage sensibility of kernels. Sample kernels dropped without a ladder (free fall) had a significantly higher average percentage breakage of 13.80%. In the use of the cushion box, the average kernel breakage was calculated to be 11.41%, which was decreased by about 17% more than the free fall. Sample kernels dropped with the closed let-down ladder had a lower average breakage of 7.26%, which showed that the closed let-down ladder significantly helped to reduce mechanical damage to corn kernels by about 47% comparing free fall and by about 37% than the use of the cushion box. The amounts of kernel damage increased significantly with increasing drop height and decreasing moisture content, but the use of the cushion box and closed let-down ladder systems somewhat reduced the adverse effect of the above factors. To minimize mechanical damage to kernels as they fall into the bin, a grain let-down ladder should be installed in the bin so that it can receive kernels from the filling spout with minimum damage. Empirical models were developed for the dependency of damage to corn kernels due to the impact caused by free fall on the drop height and moisture content at different drop methods.

11.
Methods Mol Biol ; 2567: 39-62, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36255694

RESUMO

Genetic editing of hematopoietic stem and progenitor cells can be employed to understand gene-function relationships underlying hematopoietic cell biology, leading to new therapeutic approaches to treat disease. The ability to collect, purify, and manipulate primary cells outside the body permits testing of many different gene editing approaches. RNA-guided nucleases, such as CRISPR, have revolutionized gene editing based simply on Watson-Crick base-pairing, employed to direct activity to specific genomic loci. Given the ease and affordability of synthetic, custom RNA guides, testing of precision edits or large random pools in high-throughput screening studies is now widely available. With the ever-growing number of CRISPR nucleases being discovered or engineered, researchers now have a plethora of options for directed genomic change, including single base edits, nicks or double-stranded DNA cuts with blunt or staggered ends, as well as the ability to target CRISPR to other cellular oligonucleotides such as RNA or mitochondrial DNA. Except for single base editing strategies, precise rewriting of larger segments of the genetic code requires delivery of an additional component, templated DNA oligonucleotide(s) encoding the desired changes flanked by homologous sequences that permit recombination at or near the site of CRISPR activity. Altogether, the ever-growing CRISPR gene editing toolkit is an invaluable resource. This chapter outlines available technologies and the strategies for applying CRISPR-based editing in hematopoietic stem and progenitor cells.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Sistemas CRISPR-Cas/genética , Oligonucleotídeos , Células-Tronco , RNA , DNA Mitocondrial
12.
Plant Methods ; 18(1): 142, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36550504

RESUMO

BACKGROUND: Corn seeds have a high susceptibility to mechanical damage due to their large size and mass. The main purpose of this study was to evaluate the effects of the cushion box and closed let-down ladder usage in minimizing the negative influence of the free fall on the storage potential of corn seeds. Corn seeds were evaluated for the extent of physiological damage by measuring the seed deterioration by the accelerated aging test (percentage loss in germination in the accelerated aging test), using three drop methods (free fall, with cushion box, and with closed let-down ladder) at three drop heights (5, 10, and 15 m) and five different moisture contents (10, 15, 20 and 25%). RESULTS: The drop methods had a significant effect on the storage potential of corn seeds. Sample seeds dropped without a ladder (free fall) had a significantly higher average physiological quality loss of 13.87% (loss in accelerated aging germination). In the use of the cushion box, the average percentage loss in germination was calculated to be 11.38%, which was decreased by about 18% more than the free fall. Sample seeds dropped with the closed let-down ladder had a lower average percentage loss in the germination of 8.78%, which showed that the closed let-down ladder significantly helped to reduce mechanical damage to corn seeds by about 37% comparing free fall and by about 23% to the use of the cushion box. The amounts of loss in physiological quality of corn seeds increased significantly with increasing drop height and moisture content, but the use of the cushion box and closed let-down ladder systems somewhat reduced the adverse effect of the above factors. Empirical models were developed for the dependency of physiological damage to corn seeds due to the impact caused by free fall, on the drop height and moisture content at different drop methods. CONCLUSIONS: To minimize mechanical damage to seeds as they fall into the bin, a let-down ladder should be installed in the bin so that it can receive seeds from the filling spout with minimum damage.

13.
Front Oncol ; 12: 1023565, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36686736

RESUMO

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally, with nearly half of patients detected in the advanced stages. This is due to the fact that symptoms associated with CRC often do not appear until the cancer has reached an advanced stage. This suggests that CRC is a cancer with a slow progression, making it curable and preventive if detected in its early stage. Therefore, there is an urgent clinical need to improve CRC early detection and personalize therapy for patients with this cancer. Recently, liquid biopsy as a non-invasive or nominally invasive approach has attracted considerable interest for its real-time disease monitoring capability through repeated sample analysis. Several studies in CRC have revealed the potential for liquid biopsy application in a real clinical setting using circulating RNA/miRNA, circulating tumor cells (CTCs), exosomes, etc. However, Liquid biopsy still remains a challenge since there are currently no promising results with high specificity and specificity that might be employed as optimal circulatory biomarkers. Therefore, in this review, we conferred the plausible role of less explored liquid biopsy components like mitochondrial DNA (mtDNA), organoid model of CTCs, and circulating cancer-associated fibroblasts (cCAFs); which may allow researchers to develop improved strategies to unravel unfulfilled clinical requirements in CRC patients. Moreover, we have also discussed immunotherapy approaches to improve the prognosis of MSI (Microsatellite Instability) CRC patients using neoantigens and immune cells in the tumor microenvironment (TME) as a liquid biopsy approach in detail.

14.
Biomed Mater ; 16(5)2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34330118

RESUMO

In this study, we evaluated cardiomyogenic differentiation of electromechanically stimulated rat bone marrow-derived stem cells (rt-BMSCs) on an acellular bovine pericardium (aBP) and we looked at the functioning of this engineered patch in a rat myocardial infarct (MI) model. aBP was prepared using a detergent-based decellularization procedure followed by rt-BMSCs seeding, and electrical, mechanical, or electromechanical stimulations (3 millisecond pulses of 5 V cm-1at 1 Hz, 5% stretching) to enhance cardiomyogenic differentiation. Furthermore, the electromechanically stimulated patch was applied to the MI region over 3 weeks. After this period, the retrieved patch and infarct region were evaluated for the presence of calcification, inflammatory reaction (CD68), patch to host tissue cell migration, and structural sarcomere protein expressions. In conjunction with any sign of calcification, a higher number of BrdU-labelled cells, and a low level of CD68 positive cells were observed in the infarct region under electromechanically stimulated conditions compared with static conditions. More importantly, MHC, SAC, Troponin T, and N-cad positive cells were observed in both infarct region, and retrieved engineered patch after 3 weeks. In a clear alignment with other results, our developed acellular patch promoted the expression of cardiomyogenic differentiation factors under electromechanical stimulation. Our engineered patch showed a successful integration with the host tissue followed by the cell migration to the infarct region.


Assuntos
Materiais Biocompatíveis , Estimulação Elétrica , Infarto do Miocárdio , Miocárdio , Engenharia Tecidual/métodos , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos da radiação , Bovinos , Diferenciação Celular/efeitos dos fármacos , Miocárdio/citologia , Miocárdio/metabolismo , Miócitos Cardíacos/citologia , Pericárdio/citologia , Pericárdio/transplante , Ratos , Células-Tronco/citologia , Células-Tronco/efeitos da radiação
15.
Artif Cells Nanomed Biotechnol ; 48(1): 810-817, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32476515

RESUMO

Staphylococcus aureus is an important infectious factor in the food industry and hospital infections. Many methods are used for detecting bacteria but they are mostly time-consuming, poorly sensitive. In this study, a nano-biosensor based on iron nanoparticles (MNPs) was designed to detect S. aureus. MNPs were synthesized and conjugated to Biosensors. Then S. aureus was lysed and nano-biosensor (MNP-TiO2-AP-SMCC-Biosensors) was added to the lysed bacteria. After bonding the bacterial genome to the nano-biosensor, MNPs were separated by a magnet. Bacterial DNA was released from the surface of nano-biosensor and researched by Nano-drop spectrophotometry. The results of SEM and DLS revealed that the size of MNPs was 20-25 nm which increased to 38-43 nm after modification and addition of biosensors. The designed nano-biosensor was highly sensitive and specific for the detection of S. aureus. The limit of detection (LOD) was determined as 230 CFU mL-1. There was an acceptable linear correlation between bacterial concentration and absorption at 3.7 × 102-3.7× 107 whose linear diagram and regression was Y = 0.242X + 2.08 and R2 = .996. Further, in the presence of other bacteria as a negative control, it was absolutely specific. The sensitivity of the designed nano-biosensor was investigated and compared through PCR.


Assuntos
Técnicas Biossensoriais/métodos , Limite de Detecção , Nanopartículas de Magnetita/química , Fotometria , Staphylococcus aureus/isolamento & purificação , Ouro/química
16.
Mol Ther Methods Clin Dev ; 17: 796-809, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32355868

RESUMO

In vivo tracking of retrovirus-tagged blood stem and progenitor cells is used to study hematopoiesis. Two techniques are used most frequently: sequencing the locus of retrovirus insertion, termed integration site analysis, or retrovirus DNA barcode sequencing. Of these, integration site analysis is currently the only available technique for monitoring clonal pools in patients treated with retrovirus-modified blood cells. A key question is how these two techniques compare in their ability to detect and quantify clonal contributions. In this study, we assessed both methods simultaneously in a clinically relevant nonhuman primate model of autologous, myeloablative transplantation. Our data demonstrate that both methods track abundant clones; however, DNA barcode sequencing is at least 5-fold more efficient than integration site analysis. Using computational simulation to identify the sources of low efficiency, we identify sampling depth as the major factor. We show that the sampling required for integration site analysis to achieve minimal coverage of the true clonal pool is likely prohibitive, especially in cases of low gene-modified cell engraftment. We also show that early subsampling of different blood cell lineages adds value to clone tracking information in terms of safety and hematopoietic biology. Our analysis demonstrates DNA barcode sequencing as a useful guide to maximize integration site analysis interpretation in gene therapy patients.

17.
Anticancer Res ; 38(12): 6591-6606, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30504367

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers with a median survival of 6 months after diagnosis. Intrinsic resistance to chemotherapeutics and lack of effective targeted therapies are the major factors contributing to dismal prognosis. Several important genetic alterations (i.e., mutations, deletions) have been identified to be involved in the initiation and progression of pancreatic cancer, including KRAS and inactivation of tumor suppressors, such as TP53, SMAD4 and CDKN2A. Unique tumor microenvironment with excessive stroma due to desmoplastic reaction is one of the major characteristics of PDAC, promoting tumor growth and leading to treatment failures. In addition, tumor stroma represents an important biological barrier for drug delivery and successful treatment of PDAC. Small interfering RNA (siRNA) has recently emerged as a potential and targeted therapeutic approach which is now evaluated in clinical trials. However, siRNA-based therapeutics face important challenges, including rapid serum degradation, poor tumor cell uptake and cellular uptake, leading to off-target effects. Therefore, there is a great need for the development of safe and effective nanoparticles for better tumor-specific delivery of anti-cancer therapeutics. In this article, the main challenges in the treatment of pancreatic cancer and recent advancements on nano delivery systems of chemotherapeutics and gene-targeted agents, used both in preclinical and clinical trials are reviewed.


Assuntos
Carcinoma Ductal Pancreático/terapia , Terapia de Alvo Molecular , Neoplasias Pancreáticas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/etiologia , Carcinoma Ductal Pancreático/patologia , Sistemas de Liberação de Medicamentos , Predisposição Genética para Doença , Humanos , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/patologia , Transdução de Sinais/genética
19.
J Biomed Mater Res A ; 106(6): 1604-1613, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29427534

RESUMO

Neurite outgrowth and elongation of neural cells is the most important subject that is considered in nerve tissue engineering. In this regard, aligned nanofibers have taken much attention in terms of providing guidance for newly outgrown neurites. The main objective of this study was to fabricate aligned polyurethane nanofibers by electrospinning process and decorate them with gold nanoparticles to further investigate the synergistic effects of nanotopography, biological nerve growth factor (NGF) and electrical stimulations on neurite outgrowth and elongation of pheochromocytoma (PC-12) model cells. In this regard, smooth and uniform aligned polyurethane nanofibers with the average diameter of 519 ± 56 nm were fabricated and decorated with the gold nanoparticles with the average diameter of ∼50 nm. PC-12 cells were cultured on the various nanofiber surfaces inside the bio-mimetic bioreactor system and exposed either to NGF alone or combination of NGF and electrical stimulation. It was found that 50 ng/mL NGF concentration is an optimal value for the stimulation of neurite outgrowth. After 4 days of culture under 100 mV, 10 ms electrical stimulation in 1 h/day period it was found that the gold nanoparticle decorated aligned polyurethane nanofibers increased the neurite outgrowth and elongation more with the combinational NGF and electrical stimulation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1604-1613, 2018.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Nanofibras/química , Crescimento Neuronal , Poliuretanos/química , Alicerces Teciduais/química , Animais , Nanopartículas Metálicas/ultraestrutura , Nanofibras/ultraestrutura , Células PC12 , Ratos , Propriedades de Superfície , Engenharia Tecidual
20.
Expert Opin Drug Discov ; 12(4): 391-406, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28165829

RESUMO

INTRODUCTION: Conventional administration of antibacterial drugs to the human body can cause vital problems such as dose dependent systemic toxicity and bacterial resistance which prevent the healing process. In this regard, recent studies have been devoted to producing nanofiber based antibacterial drug delivery approaches which surpass bacterial resistance and toxicological issues. Areas covered: This review summarizes latest developments in the production of antibacterial nanofibers, nanofiber based antibacterial action mechanisms and release profiles of nanofibers. In the first section, key challenges of antibacterial nanofibers and release and non-release antibacterial action mechanisms of nanofibers are highlighted. In the second section, routes of antibacterial nanofiber design have been given. Factors affecting drug release mechanisms have been discussed elaborately in the final section. Literature was surveyed from research articles, standard sources (WOS and Scopus) and clinical trials. Expert opinion: New generation nanofibers provide high drug loading capacity and efficiency with their high surface area and tunable pore size. They also enable sustained and controlled release of antibacterial drugs with basic (direct incorporation, physically adsorption or chemically surface modification of antibacterial drugs), advanced (core-shell structure, nanoparticle decorated and multidrug loaded) and smart (stimuli responsive) antibacterial nanofiber design strategies.


Assuntos
Antibacterianos/administração & dosagem , Desenho de Fármacos , Nanofibras , Animais , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Preparações de Ação Retardada , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Farmacorresistência Bacteriana , Humanos
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