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1.
Plant Mol Biol ; 114(4): 79, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935184

RESUMO

Plants are expected to play a critical role in the biological life support systems of crewed spaceflight missions, including in the context of upcoming missions targeting the Moon and Mars. Therefore, understanding the response of plants to spaceflight is essential for improving the selection and engineering of plants and spaceflight conditions. In particular, understanding the root-tip's response to spaceflight is of importance as it is the center of orchestrating the development of the root, the primary organ for the absorption of nutrients and anchorage. GLDS-120 is a pioneering study by Paul et al. that used transcriptomics to evaluate the spaceflight response of the root-tip of the model plant Arabidopsis thaliana in dark and light through separate analyses of three genotype groups (Wassilewskija, Columbia-0, and Columbia-0 PhyD) and comparison of genotype responses. Here, we provide a complementary analysis of this dataset through a combined analysis of all samples while controlling for the genotypes in a paired analysis. We identified a robust transcriptional response to spaceflight with 622 DEGs in light and 200 DEGs in dark conditions. Gene enrichment analysis identified 37 and 13 significantly enriched terms from biological processes in light and dark conditions, respectively. Prominent enrichment for hypoxia-related terms in both conditions suggests hypoxia is a key stressor for root development during spaceflight. Additional enriched terms in light conditions include the circadian cycle, light response, and terms for the metabolism of flavonoid and indole-containing compounds. These results further our understanding of plants' responses to the spaceflight environment.


Assuntos
Arabidopsis , Regulação da Expressão Gênica de Plantas , Voo Espacial , Arabidopsis/genética , Arabidopsis/fisiologia , Arabidopsis/crescimento & desenvolvimento , Genótipo , Perfilação da Expressão Gênica , Meristema/genética , Meristema/crescimento & desenvolvimento , Meristema/efeitos da radiação , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/efeitos da radiação , Transcriptoma , Luz , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo
2.
BMC Biotechnol ; 24(1): 10, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38439037

RESUMO

Polymicrobial communities lead to worsen the wound infections, due to mixed biofilms, increased antibiotic resistance, and altered virulence production. Promising approaches, including enzymes, may overcome the complicated condition of polymicrobial infections. Therefore, this study aimed to investigate Staphopain A-mediated virulence and resistance alteration in an animal model of Staphylococcus aureus and Pseudomonas aeruginosa co-infection. S. aureus and P. aeruginosa were co-cultured on the L-929 cell line and wound infection in an animal model. Then, recombinant staphopain A was purified and used to treat mono- and co-infections. Following the treatment, changes in virulence factors and resistance were investigated through phenotypic methods and RT-PCR. Staphopain A resulted in a notable reduction in the viability of S. aureus and P. aeruginosa. The biofilm formed in the wound infection in both animal model and cell culture was disrupted remarkably. Moreover, the biofilm-encoding genes, quorum sensing regulating genes, and virulence factors (hemolysin and pyocyanin) controlled by QS were down-regulated in both microorganisms. Furthermore, the resistance to vancomycin and doripenem decreased following treatment with staphopain A. According to this study, staphopain A might promote wound healing and cure co-infection. It seems to be a promising agent to combine with antibiotics to overcome hard-to-cure infections.


Assuntos
Coinfecção , Infecção dos Ferimentos , Animais , Virulência , Pseudomonas aeruginosa/genética , Staphylococcus aureus/genética , Coinfecção/tratamento farmacológico , Fatores de Virulência/genética , Modelos Animais , Resistência Microbiana a Medicamentos , Infecção dos Ferimentos/tratamento farmacológico
3.
BMC Biotechnol ; 23(1): 39, 2023 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-37723466

RESUMO

Staphylococcus aureus is a unique challenge for the healthcare system because it can form biofilms, is resistant to the host's immune system, and is resistant to numerous antimicrobial therapies. The aim of this study was to investigate the effect of poly (lactic-co-glycolic acid) (PLGA) polymer nanoparticles loaded with vancomycin and conjugated with lysostaphin (PLGA-VAN-LYS) on inhibiting S. aureus biofilm formation. Nano drug carriers were produced using the double emulsion evaporation process. we examined the physicochemical characteristics of the nanoparticles, including particle size, polydispersity index (PDI), zeta potential, drug loading (DL), entrapment efficiency (EE), Lysostaphin conjugation efficiency (LCE), and shape. The effect of the nano drug carriers on S. aureus strains was evaluated by determining the minimum inhibitory concentration (MIC), conducting biofilm formation inhibition studies, and performing agar well diffusion tests. The average size, PDI, zeta potential, DL, EE, and LCE of PLGA-VAN-LYS were 320.5 ± 35 nm, 0.270 ± 0.012, -19.5 ± 1.3 mV, 16.75 ± 2.5%, 94.62 ± 2.6%, and 37% respectively. Both the agar well diffusion and MIC tests did not show a distinction between vancomycin and the nano drug carriers after 72 h. However, the results of the biofilm analysis demonstrated that the nano drug carrier had a stronger inhibitory effect on biofilm formation compared to the free drug. The use of this technology for treating hospital infections caused by the Staphylococcus bacteria may have favorable effects on staphylococcal infections, considering the efficacy of the nano medicine carrier developed in this study.


Assuntos
Infecções Estafilocócicas , Vancomicina , Humanos , Vancomicina/farmacologia , Glicóis , Staphylococcus aureus , Ágar , Lisostafina , Polímeros , Biofilmes
4.
Mol Biol Rep ; 50(5): 4675-4686, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37022526

RESUMO

INTRODUCTION: Multiple sclerosis (MS) is a progressive inflammatory autoimmune disease that involves young individuals. The drug delivery systems now are available for this disease have chronic and non-targeted effects on the patients. Because of the presence of BBB (blood-brain-barrier), their concentration in the CNS (central nervous system) is low. Because of this flaw, it is critical to use innovative active targeted drug delivery methods. RESULT: Platelets are blood cells that circulate freely and play an important role in blood hemostasis. In this review, we emphasize the various roles of activated platelets in the inflammatory condition to recruit other cells to the injured area and limit inflammation. Besides, the activated platelets in the different stages of the MS disease play a significant role in limiting the progression of inflammation in the peripheral area and CNS. DISCUSSION: This evidence indicates that a platelet-based drug delivery system can be an efficient biomimetic candidate for drug targeting to the CNS and limiting the inflammation in the peripheral and central areas for MS therapy.


Assuntos
Esclerose Múltipla , Humanos , Esclerose Múltipla/tratamento farmacológico , Sistema Nervoso Central , Plaquetas , Barreira Hematoencefálica , Inflamação
5.
Molecules ; 28(9)2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37175267

RESUMO

Cadmium sulfide nanoparticles (CdS NPs) have been employed in various fields of nanobiotechnology due to their proven biomedical properties. They are unique in their properties due to their size and shape, and they are popular in the area of biosensors, bioimaging, and antibacterial and anticancer applications. Most CdS NPs are generally synthesized through chemical, physical, or biological methods. Among these methods, biogenic synthesis has attracted more attention due to its high efficiency, environmental friendliness, and biocompatibility features. The green approach was found to be superior to other methods in terms of maintaining the structural characteristics needed for optimal biomedical applications. The size and coating components of CdS NPs play a crucial role in their biomedical activities, such as anticancer, antibacterial, bioimaging, and biosensing applications. CdS NPs have gained significant interest in bioimaging due to their desirable properties, including good dispersion, cell integrity preservation, and efficient light scattering. Despite these, further studies are necessary, particularly in vivo studies to reduce NPs' toxicity. This review discusses the different methods of synthesis, how CdS NPs are characterized, and their applications in the biomedical field.


Assuntos
Compostos de Cádmio , Nanopartículas , Nanopartículas/química , Compostos de Cádmio/química , Sulfetos/química , Antibacterianos/química
6.
Gerontology ; 68(2): 224-233, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33971647

RESUMO

BACKGROUND: Cognitive frailty (CF), defined as the simultaneous presence of cognitive impairment and physical frailty, is a clinical symptom in early-stage dementia with promise in assessing the risk of dementia. The purpose of this study was to use wearables to determine the most sensitive digital gait biomarkers to identify CF. METHODS: Of 121 older adults (age = 78.9 ± 8.2 years, body mass index = 26.6 ± 5.5 kg/m2) who were evaluated with a comprehensive neurological exam and the Fried frailty criteria, 41 participants (34%) were identified with CF and 80 participants (66%) were identified without CF. Gait performance of participants was assessed under single task (walking without cognitive distraction) and dual task (walking while counting backward from a random number) using a validated wearable platform. Participants walked at habitual speed over a distance of 10 m. A validated algorithm was used to determine steady-state walking. Gait parameters of interest include steady-state gait speed, stride length, gait cycle time, double support, and gait unsteadiness. In addition, speed and stride length were normalized by height. RESULTS: Our results suggest that compared to the group without CF, the CF group had deteriorated gait performances in both single-task and dual-task walking (Cohen's effect size d = 0.42-0.97, p < 0.050). The largest effect size was observed in normalized dual-task gait speed (d = 0.97, p < 0.001). The use of dual-task gait speed improved the area under the curve (AUC) to distinguish CF cases to 0.76 from 0.73 observed for the single-task gait speed. Adding both single-task and dual-task gait speeds did not noticeably change AUC. However, when additional gait parameters such as gait unsteadiness, stride length, and double support were included in the model, AUC was improved to 0.87. CONCLUSIONS: This study suggests that gait performances measured by wearable sensors are potential digital biomarkers of CF among older adults. Dual-task gait and other detailed gait metrics provide value for identifying CF above gait speed alone. Future studies need to examine the potential benefits of gait performances for early diagnosis of CF and/or tracking its severity over time.


Assuntos
Fragilidade , Velocidade de Caminhada , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Cognição , Fragilidade/diagnóstico , Marcha , Humanos , Caminhada
7.
Nanomedicine ; 44: 102575, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35714923

RESUMO

A cell-based drug delivery system based on yeast-cell wall loaded with sitagliptin, a drug with an anti-inflammatory effect, was developed to control neuroinflammation associated with Alzheimer's disease. The optimized nanoparticles had a spherical shape with a negative surface charge, and were shown to be less toxic than the carrier and sitagliptin. Moreover, the nanoparticles caused anti-inflammatory effects against tumor necrosis factor-alpha in mice model of neuroinflammation. The pharmacokinetics study showed the brain concentration of drug in the nanoparticles group was much higher than in the control group. To evaluate the effect of P-glycoprotein on brain entry of sitagliptin, the experiment was repeated with verapamil, as a P-glycoprotein inhibitor. Brain concentration of the nanoparticles group remained approximately unchanged, proving the "Trojan Horse" effect of the developed nanocarriers. The results are promising for using yeast-cell wall as a carrier for targeted delivery to immune cells for the management of inflammation.


Assuntos
Doença de Alzheimer , Subfamília B de Transportador de Cassetes de Ligação de ATP/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Animais , Anti-Inflamatórios/uso terapêutico , Parede Celular/metabolismo , Camundongos , Doenças Neuroinflamatórias , Saccharomyces cerevisiae , Fosfato de Sitagliptina/farmacologia , Fosfato de Sitagliptina/uso terapêutico
8.
Small ; 17(12): e2006484, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33577127

RESUMO

Nanotechnology has provided great opportunities for managing neoplastic conditions at various levels, from preventive and diagnostic to therapeutic fields. However, when it comes to clinical application, nanoparticles (NPs) have some limitations in terms of biological stability, poor targeting, and rapid clearance from the body. Therefore, biomimetic approaches, utilizing immune cell membranes, are proposed to solve these issues. For example, macrophage or neutrophil cell membrane coated NPs are developed with the ability to interact with tumor tissue to suppress cancer progression and metastasis. The functionality of these particles largely depends on the surface proteins of the immune cells and their preserved function during membrane extraction and coating process on the NPs. Proteins on the outer surface of immune cells can render a wide range of activities to the NPs, including prolonged blood circulation, remarkable competency in recognizing antigens for enhanced targeting, better cellular interactions, gradual drug release, and reduced toxicity in vivo. In this review, nano-based systems coated with immune cells-derived membranous layers, their detailed production process, and the applicability of these biomimetic systems in cancer treatment are discussed. In addition, future perspectives and challenges for their clinical translation are also presented.


Assuntos
Materiais Biomiméticos , Nanopartículas , Neoplasias , Biomimética , Membrana Celular , Humanos , Neoplasias/terapia , Fototerapia
9.
Chembiochem ; 22(13): 2306-2318, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33884725

RESUMO

Cytotoxic aggregation of misfolded ß-amyloid (Aß) proteins is the main culprit suspected to be behind the development of Alzheimer's disease (AD). In this study, Aß interactions with the novel two-dimensional (2D) covalent organic frameworks (COFs) as therapeutic options for avoiding ß-amyloid aggregation have been investigated. The results from multi-scale atomistic simulations suggest that amine-functionalized COFs with a large surface area (more than 1000 m2 /gr) have the potential to prevent Aß aggregation. Gibb's free energy analysis confirmed that COFs could prevent protofibril self-assembly in addition to inhibiting ß-amyloid aggregation. Additionally, it was observed that the amine functional group and high contact area could improve the inhibitory effect of COFs on Aß aggregation and enhance the diffusivity of COFs through the blood-brain barrier (BBB). In addition, microsecond coarse-grained (CG) simulations with three hundred amyloids reveal that the presence of COFs creates instability in the structure of amyloids and consequently prevents the fibrillation. These results suggest promising applications of engineered COFs in the treatment of AD and provide a new perspective on future experimental research.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/química , Estruturas Metalorgânicas/química , Barreira Hematoencefálica/metabolismo , Simulação por Computador , Dissecação , Ligação Proteica , Conformação Proteica , Relação Estrutura-Atividade
10.
Chem Soc Rev ; 49(4): 1253-1321, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-31998912

RESUMO

Studies of nanosized forms of bismuth (Bi)-containing materials have recently expanded from optical, chemical, electronic, and engineering fields towards biomedicine, as a result of their safety, cost-effective fabrication processes, large surface area, high stability, and high versatility in terms of shape, size, and porosity. Bi, as a nontoxic and inexpensive diamagnetic heavy metal, has been used for the fabrication of various nanoparticles (NPs) with unique structural, physicochemical, and compositional features to combine various properties, such as a favourably high X-ray attenuation coefficient and near-infrared (NIR) absorbance, excellent light-to-heat conversion efficiency, and a long circulation half-life. These features have rendered bismuth-containing nanoparticles (BiNPs) with desirable performance for combined cancer therapy, photothermal and radiation therapy (RT), multimodal imaging, theranostics, drug delivery, biosensing, and tissue engineering. Bismuth oxyhalides (BiOx, where X is Cl, Br or I) and bismuth chalcogenides, including bismuth oxide, bismuth sulfide, bismuth selenide, and bismuth telluride, have been heavily investigated for therapeutic purposes. The pharmacokinetics of these BiNPs can be easily improved via the facile modification of their surfaces with biocompatible polymers and proteins, resulting in enhanced colloidal stability, extended blood circulation, and reduced toxicity. Desirable antibacterial effects, bone regeneration potential, and tumor growth suppression under NIR laser radiation are the main biomedical research areas involving BiNPs that have opened up a new paradigm for their future clinical translation. This review emphasizes the synthesis and state-of-the-art progress related to the biomedical applications of BiNPs with different structures, sizes, and compositions. Furthermore, a comprehensive discussion focusing on challenges and future opportunities is presented.


Assuntos
Bismuto/química , Nanopartículas Metálicas/química , Nanomedicina Teranóstica , Técnicas Biossensoriais , Regeneração Óssea , Meios de Contraste/síntese química , Meios de Contraste/química , Humanos , Nanopartículas Metálicas/uso terapêutico , Imagem Multimodal , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Fototerapia
11.
Pharm Res ; 37(8): 160, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32747991

RESUMO

PURPOSE: The aim of this study was to introduce a smart and responsive drug carrier for Doxorubicin (DOX) and Paclitaxel (PAX) for desirable therapeutic application. METHOD: Loading and releasing of DOX and PAX from smart and pH-sensitive functionalized single-walled carbon nanotube (SWCNTs) and graphene carriers have been simulated by molecular dynamics. The influences of chitosan polymer on proposed carriers have been studied, and both carriers were functionalized with carboxyl groups to improve the loading and releasing properties of the drugs. RESULTS: The results showed that DOX could be well adsorbed on both functionalized SWCNTs and graphene. In contrast, there was a weak electrostatic and Van der Waals interaction between both these drugs and carriers at cancerous tissues, which is highly favorable for cancer therapy. Adding trimethyl chitosan (TMC) polymer to carriers facilitated DOX release at acidic tissues. Furthermore, at blood pH, the PAX loaded on the functionalized SWCNTs carrier represented the highest dispersion of the drug while the DOX-graphene showed the highest concentration of the drug at a point. In addition, the mean-square displacement (MSD) results of PAX-graphene indicated that the PAX could be adsorbed quickly and be released slowly. Finally, functionalized graphene-TMC-PAX is a smart drug system with responsive behavior and controllable drug release, which are essential in cancer therapy. CONCLUSION: Simultaneous application of the carboxyl group and TMC can optimize the pH sensitivity of the SWCNTs and graphene to prepare a novel and smart drug carrier for cancer therapy.


Assuntos
Quitosana/química , Portadores de Fármacos/química , Grafite/química , Nanomedicina/métodos , Nanotubos de Carbono/química , Adsorção , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Paclitaxel/administração & dosagem , Eletricidade Estática
12.
Ann Vasc Surg ; 67: 425-436, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32209405

RESUMO

BACKGROUND: The aim of this study was to describe the applicability of the Society for Vascular Surgery (SVS) objective performance goals (OPGs) as a tool to evaluate results in the context of endovascular management of noncomplex and complex patients (i.e., end stage renal disease/history of prosthetic conduit) with chronic limb-threatening ischemia (CLTI). METHODS: Patients diagnosed with CLTI undergoing endovascular procedures from March 2016 to April 2017 were included, and medical records were examined. Patients were categorized as OPG risk (OPGR) and non-OPG risk (nOPGR) groups in accordance with the SVS performance criteria. We compared clinical events between the two groups and then further to the SVS OPGs. Thirty-day outcomes (safety) were major amputation (AMP), major adverse limb events (MALEs), and major adverse cardiovascular events (MACEs), and 1-year outcomes (efficacy) were limb salvage, MALE + 30-day perioperative death (MALE + POD), and survival. Mortality was demonstrated using Kaplan-Meier analysis. RESULTS: A total of 72 patients were included (OPGR = 58.3% vs. nOPGR = 41.7%). Mean follow-up was 20 months (range, 1-40 months). Retrograde pedal access was used in 65.2% of patients. The overall AMP rate was 2.7% (OPGR = 4.7%, nOPGR = 0%, P = 0.225, vs. SVS OPG<3%), MALE was 4.1% (OPGR = 7.1%, nOPGR = 0%, P = 0.135, vs. SVS OPG<8%), and MACE was 6.9% (OPGR = 2.3%, nOPGR = 13.3%, P = 0.071, vs. SVS OPG<8%). The limb salvage was 90.3% (OPGR = 88%, nOPGR = 93.3%, P = 0.46, vs. SVS OPG>84%), MALE + POD was 76.4% (OPGR = 78.6%, nOPGR = 73.4%, P = 0.606, vs. SVS OPG>71%), and survival was 77.7% (OPGR = 83.3%, nOPGR = 70%, P = 0.18, vs. SVS OPG>80%). CONCLUSIONS: The SVS OPGs set appropriate safety and efficacy standards as a bar for new technologies. In this series, endovascular therapy in all-comers exceeded the safety and efficacy endpoints proposed by the limited risk OPG panel.


Assuntos
Implante de Prótese Vascular , Procedimentos Endovasculares , Isquemia/cirurgia , Doença Arterial Periférica/cirurgia , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Doença Crônica , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Isquemia/diagnóstico , Isquemia/mortalidade , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/mortalidade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
14.
Bioconjug Chem ; 28(6): 1639-1648, 2017 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-28557453

RESUMO

The encapsulation of drugs to nanoparticles may offer a solution for targeted delivery. Here, we set out to engineer a self-assembling targeting ligand by combining the functional properties of human transferrin and fungal hydrophobins in a single fusion protein. We showed that human transferrin can be expressed in Nicotiana benthamiana plants as a fusion with Trichoderma reesei hydrophobins HFBI, HFBII, or HFBIV. Transferrin-HFBIV was further expressed in tobacco BY-2 suspension cells. Both partners of the fusion protein retained their functionality; the hydrophobin moiety enabled migration to a surfactant phase in an aqueous two-phase system, and the transferrin moiety was able to reversibly bind iron. Coating porous silicon nanoparticles with the fusion protein resulted in uptake of the nanoparticles in human cancer cells. This study provides a proof-of-concept for the functionalization of hydrophobin coatings with transferrin as a targeting ligand.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Proteínas Recombinantes de Fusão/metabolismo , Linhagem Celular Tumoral , Proteínas Fúngicas/genética , Humanos , Nanopartículas/uso terapêutico , Neoplasias/terapia , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/farmacocinética , Nicotiana/metabolismo , Transferrina/genética
15.
Reprod Health ; 13: 102, 2016 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-27576489

RESUMO

BACKGROUND: The purpose of this study is to assess attitudes toward premarital dating and sexual encounters in individuals aged 15-49 years in Tehran. METHODS: Utilizing the attitudes section of an original cross-sectional study (n = 755) aimed at assessing sexual health needs of adults, this paper examined personal attitudes towards premarital dating, non-sexual relationships and sexual encounters in both male and female adults aged between 15-49 years. Multi-stage cluster random sampling and a validated/reliable questionnaire were used. Descriptive, bivariate and multivariate analyses were conducted using statistical software. RESULTS: The results indicated that the majority of the participants were supportive of dating. Almost three-fourths of the males were more positively inclined towards non-sexual, yet tactile, affectionate interactions between unmarried males and females as opposed to only half of the females (70 % vs. 50.5 %). Also, males held significantly more liberal attitudes than females in their acceptance of premarital sex. On preserving virginity prior to marriage, 43 % of the males felt that it was important for a female to be a virgin, whereas only 26 % felt it was important for males to remain a virgin. Interestingly, more females (61 %) supported the importance of a female's virginity compared with the importance of males' virginity (48 %). This study showed that, being a male, of a younger age, single, and being less religious or being secular were important determinants of a liberal sexual attitude. CONCLUSION: These results might reflect a socio-cultural transition in the sexual attitudes of different age groups of participants - a phenomenon that will need empirical studies to unpack in the Iranian socio-cultural context.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Assunção de Riscos , Comportamento Sexual/psicologia , Comportamento Sexual/estatística & dados numéricos , Adolescente , Adulto , Atitude , Estudos Transversais , Feminino , Humanos , Relações Interpessoais , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Gravidez , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
16.
Langmuir ; 30(8): 2196-205, 2014 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-24517629

RESUMO

Thermally hydrocarbonized porous silicon (THCPSi) microparticles were loaded with indomethacin (IMC) and griseofulvin (GSV) using three different payloads between 6.2-19.5 and 6.2-11.4 wt %, respectively. The drug loading parameters were selected to avoid crystallization of the drug molecules on the external surface of the particles that would block the pore entrances. The successfulness of the loadings was verified with TG, DSC, and XRPD measurements. The effects of the confinement of IMC and GSV into the small mesopores of THCPSi were analyzed with helium pycnometry, FTIR, and NMR spectroscopy. The results showed the density of the THCPSi loaded drugs to be ca. 10% lower than the bulk crystalline forms, while a melt quenched amorphous drugs showed a density reduction of 3-7.5%. DSC and FTIR results confirmed that the drugs reside in an amorphous form within the THCPSi pores. Similar results were obtained with NMR, which also indicated that IMC may reside as both amorphous clusters and individual molecules within the pores. The (1)H transverse relaxation times (T2) of amorphous and THCPSi loaded drugs showed IMC relaxation times of 0.28 ms for both the cases, whereas for GSV the values were 0.32 and 0.39 ms, respectively, indicating similar limited mobility in both cases. The results indicated that strong drug-carrier interactions were not necessary for stabilizing the amorphous state of the adsorbed drug. Dissolution tests using biorelevant media, fasted state simulated intestinal fluid (FaSSIF) and simulated gastric fluid (SGF), showed that THCPSi-loaded IMC and GSV were rapidly released in FaSSIF with comparable rates to the amorphous forms, whereas in SGF the THCPSi reduced the pH dependency in the dissolution of IMC.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Suco Gástrico/química , Griseofulvina/química , Indometacina/química , Silício/química , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Porosidade , Espectroscopia de Infravermelho com Transformada de Fourier
17.
J Immunol ; 188(9): 4297-304, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22407918

RESUMO

Human embryonic stem cell-derived dendritic cells (hESC-DCs) may potentially provide a platform to generate "off-the-shelf" therapeutic cancer vaccines. To apply hESC-DCs for cancer immunotherapy in a semiallogeneic setting, it is crucial for these cells to "jump-start" adaptive antitumor immunity before their elimination by host alloreaction. In this study, we investigated whether CD1d upregulation in hESC-DCs may exploit invariant NKT (iNKT) cell adjuvant activity and boost antitumor immunity. Using a baculoviral vector carrying the CD1d gene, we produced CD1d-overexpressing hESC-DCs and demonstrated that the upregulated CD1d was functional in presenting α-galactosylceramide for iNKT cell expansion. Pulsed with melanoma Ag recognized by T cell 1 peptide, the CD1d-overexpressing hESC-DCs displayed enhanced capability to prime CD8(+) T cells without relying on α-galactosylceramide loading. Blocking the CD1d with Ab reduced the immunogenicity, suggesting the importance of hESC-DC and iNKT cell interaction in this context. The CD1d-overexpressing hESC-DCs also induced a proinflammatory cytokine profile that may favor the T cell priming. Moreover, a similar immunostimulatory effect was observed when the CD1d upregulation strategy was applied in human monocyte-derived dendritic cells. Therefore, our study suggests that the upregulation of CD1d in hESC-DCs provides a novel strategy to enhance their immunogenicity. This approach holds potential for advancing the application of hESC-DCs into human cancer immunotherapy.


Assuntos
Antígenos CD1d/imunologia , Comunicação Celular/imunologia , Células Dendríticas/imunologia , Células-Tronco Embrionárias/imunologia , Regulação para Cima/imunologia , Animais , Antígenos CD1d/biossíntese , Antígenos CD1d/genética , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/metabolismo , Vacinas Anticâncer/genética , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/metabolismo , Comunicação Celular/genética , Linhagem Celular Tumoral , Células Dendríticas/citologia , Células Dendríticas/metabolismo , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Humanos , Camundongos , Células T Matadoras Naturais/citologia , Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/metabolismo , Regulação para Cima/genética
18.
Macromol Rapid Commun ; 35(6): 624-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24497275

RESUMO

Currently, developing a stable nanocarrier with high cellular internalization and low toxicity is a key bottleneck in nanomedicine. Here, we have developed a successful method to covalently conjugate poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) copolymer on the surface of (3-aminopropyl)triethoxysilane-functionalized thermally carbonized porous silicon nanoparticles (APSTCPSi NPs), forming a surface negatively charged nanovehicle with unique properties. This polymer conjugated NPs could modify surface smoothness, charge, and hydrophilicity of the developed NPs, leading to considerable improvement in the colloidal and plasma stabilities via enhanced suspensibility and charge repulsion. Furthermore, despite the surface negative charge of the polymer-conjugated NPs, the cellular internalization was increased in both MDA-MB-231 and MCF-7 breast cancer cells. These results provide a proof-of-concept evidence that such polymer-based PSi nanocomposite can be extensively used as a promising candidate for intracellular drug delivery.


Assuntos
Células/citologia , Nanopartículas/química , Polímeros/química , Silício/química , Adesão Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Humanos , Porosidade
19.
Hemoglobin ; 38(1): 19-23, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24274135

RESUMO

The marginal zones of the Caspian Sea and the Persian Gulf have a higher prevalence of thalassemia compared to other regions of Iran. This disease has disabled many people and resulted in increasing health care costs. The aim of this study was to assess the incidence of ß-thalassemia (ß-thal) and to evaluate the outcome of applied preventive strategies over a 14-year period in Fars Province, Southern Iran. This cross-sectional study comprised all new cases of ß-thal recorded during 1997-2011. The data were obtained from the Non-Communicable Diseases Surveillance Department of Shiraz University of Medical Sciences, Shiraz, Iran, and are presented as mean ± standard deviation (SD). The Fars Health Network System screened 840 686 males and females applying for marriage certificates. Among the carriers, 50.5% cancelled their marriages, 42.5% married, and 7.0% did not show up at the clinics. The rate of cancelled marriages has reduced since 2000, when marriage candidates were given the option of prenatal diagnosis. From 2000 to 2011, a total of 3539 married couples were referred for prenatal diagnosis. Of these, 806 fetuses were found to carry thalassemia and 800 aborted. It is impressive to note that while 101 cases of thalassemia were recorded in 1997, this figure was reduced to two cases by 2011. This study has established that an integrated primary health care approach, with good infrastructure for implementing successful strategies, can significantly reduce the incidence of ß-thal.


Assuntos
Talassemia beta/epidemiologia , Adulto , Estudos Transversais , Feminino , Humanos , Incidência , Irã (Geográfico)/epidemiologia , Masculino , Programas de Rastreamento , Gravidez , Diagnóstico Pré-Natal , Prevalência , Adulto Jovem , Talassemia beta/diagnóstico , Talassemia beta/prevenção & controle
20.
ACS Biomater Sci Eng ; 10(3): 1207-1234, 2024 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-38416058

RESUMO

Biomaterials possess distinctive properties, notably their ability to encapsulate active biological products while providing biocompatible support. The immune system plays a vital role in preventing cancer recurrence, and there is considerable demand for an effective strategy to prevent cancer recurrence, necessitating effective strategies to address this concern. This review elucidates crucial cellular signaling pathways in cancer recurrence. Furthermore, it underscores the potential of biomaterial-based tools in averting or inhibiting cancer recurrence by modulating the immune system. Diverse biomaterials, including hydrogels, particles, films, microneedles, etc., exhibit promising capabilities in mitigating cancer recurrence. These materials are compelling candidates for cancer immunotherapy, offering in situ immunostimulatory activity through transdermal, implantable, and injectable devices. They function by reshaping the tumor microenvironment and impeding tumor growth by reducing immunosuppression. Biomaterials facilitate alterations in biodistribution, release kinetics, and colocalization of immunostimulatory agents, enhancing the safety and efficacy of therapy. Additionally, how the method addresses the limitations of other therapeutic approaches is discussed.


Assuntos
Materiais Biocompatíveis , Neoplasias , Humanos , Materiais Biocompatíveis/uso terapêutico , Distribuição Tecidual , Sistemas de Liberação de Medicamentos , Imunoterapia , Neoplasias/tratamento farmacológico , Microambiente Tumoral
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