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1.
Nanomedicine ; 60: 102757, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38889854

RESUMO

Surgical site infection (SSI) significantly affects patient recovery time, health outcomes and quality of life which is closely associated with the use of implants or mesh. Sutures are the most frequently used implants that play a significant role in the development of SSI. Studies have demonstrated that the administration of effective bactericidal and anti-inflammatory treatments can significantly decrease the incidence of SSI. To address this concern, a versatile suture was engineered by coating MoO3-X nanodots in this study. The incorporation of MoO3-X nanodots endowed the suture with desirable antibacterial and anti-inflammatory properties that were evaluated in in vitro and in vivo experiments. The results showed its remarkable ability to facilitate wound healing and prevent SSI through its dual action of combating bacterial infection and reducing inflammation. These findings highlight the promising potential of this multifunctional surgical suture as a versatile tool to promote better outcomes in surgical procedures.

2.
Small ; 18(10): e2107137, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34927361

RESUMO

Diabetic ulcers (DUs) appearing as chronic wounds are difficult to heal due to the oxidative stress in the wound microenvironment and their high susceptibility to bacterial infection. A routine treatment combining surgical debridement with anti-infection therapy is widely used for treating DUs in the clinic, but hardly offers a satisfying wound healing outcome. It is known that a long-term antibiotic treatment may also lead to the drug resistance of pathogens. To address these challenges, new strategies combining both reactive oxygen species (ROS) scavenging and bacterial sterilization have been proposed for fighting against DUs. Following this idea, oxygen deficient molybdenum-based nanodots (MoO3-X ) for healing the DUs are reported. The ROS scavenging ability of MoO3-X nanodots is investigated and the antibacterial property of the nanodots is also demonstrated. The systematic cell and animal experimental results indicate that the MoO3-X nanodots can effectively reduce inflammation, promote epithelial cell regeneration, accelerate angiogenesis, and facilitate DUs recovery. Most importantly, they present excellent capacity to diminish infection of methicillin-resistant Staphylococcus aureus, manifesting the potent application prospect of MoO3-X nanodots for diabetic wound therapy.


Assuntos
Diabetes Mellitus , Staphylococcus aureus Resistente à Meticilina , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Espécies Reativas de Oxigênio , Úlcera , Cicatrização
3.
BMC Neurol ; 21(1): 325, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34425782

RESUMO

BACKGROUND: Few studies focused on the functional outcomes of patients at 3 months after receiving intravenous thrombolysis, anticoagulation, or antiplatelet therapy within 4.5 h of onset of the cardiogenic cerebral embolism (CCE) subtype. METHODS: The purpose of this retrospective study was to analyse the clinical data of patients with acute CCE and compare the 3-month functional prognoses of patients after administration of different antithrombotic therapies within 4.5 h of stroke onset. A total of 335 patients with CCE hospitalized in our institution were included in this study. The patients were stratified according to the hyperacute treatment received, and baseline clinical and laboratory data were analysed. A 3-month modified Rankin scale (mRS) score of 0-2 was defined as an excellent functional outcome. RESULTS: A total of 335 patients were divided into thrombolytic (n = 78), anticoagulant (n = 88), and antiplatelet therapy groups (n = 169). A total of 164 patients had a good prognosis at 3 months (mRS ≤ 2). After adjustments were made for age and National Institute of Health Stroke Scale (NIHSS) score, each group comprised 38 patients, and there were no significant differences in sex composition, complications, lesion characteristics, or Oxfordshire Community Stroke Project (OSCP) classification among the three groups. The plasma D-dimer level (µg/ml) in the thrombolytic group was significantly higher than those in the anticoagulant and antiplatelet groups [3.07 (1.50,5.62), 1.33 (0.95,1.89), 1.61 (0.76,2.96), P < 0.001]. After one week of treatment, the reduction in NIHSS in the thrombolytic group was significantly greater than those in the other two groups [3.00 (1.00, 8.00), 1.00 (0.00, 5.00), 1.00 (0.00, 2.00), P = 0.025]. A total of 47 patients (41.2 %) had an mRS score of ≤ 2 at 3 months, and 23 patients died (20.2 %). There was no significant difference in the proportion of patients with a good prognosis or the mortality rate among the three groups (P = 0.363, P = 0.683). CONCLUSIONS: Thrombolytic therapy is effective at improving short-term and 3-month prognoses. Anticoagulant therapy may be a safe and effective treatment option for patients with the cardiac stroke subtype who fail to receive intravenous recombinant tissue plasminogen activator (r-tPA) thrombolysis within 4.5 h in addition to antiplatelet therapy, as recommended by the guidelines.


Assuntos
Isquemia Encefálica , Embolia Intracraniana , Acidente Vascular Cerebral , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Humanos , Embolia Intracraniana/complicações , Embolia Intracraniana/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do Tratamento
4.
J Nanobiotechnology ; 19(1): 369, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34789288

RESUMO

BACKGROUND: Fluorescence imaging as the beacon for optical navigation has wildly developed in preclinical studies due to its prominent advantages, including noninvasiveness and superior temporal resolution. However, the traditional optical methods based on ultraviolet (UV, 200-400 nm) and visible light (Vis, 400-650 nm) limited by their low penetration, signal-to-noise ratio, and high background auto-fluorescence interference. Therefore, the development of near-infrared-II (NIR-II 1000-1700 nm) nanoprobe attracted significant attentions toward in vivo imaging. Regrettably, most of the NIR-II fluorescence probes, especially for inorganic NPs, were hardly excreted from the reticuloendothelial system (RES), yielding the anonymous long-term circulatory safety issue. RESULTS: Here, we develop a facile strategy for the fabrication of Nd3+-doped rare-earth core-shell nanoparticles (Nd-RENPs), NaGdF4:5%Nd@NaLuF4, with strong emission in the NIR-II window. What's more, the Nd-RENPs could be quickly eliminated from the hepatobiliary pathway, reducing the potential risk with the long-term retention in the RES. Further, the Nd-RENPs are successfully utilized for NIR-II in vivo imaging and magnetic resonance imaging (MRI) contrast agents, enabling the precise detection of breast cancer. CONCLUSIONS: The rationally designed Nd-RENPs nanoprobes manifest rapid-clearance property revealing the potential application toward the noninvasive preoperative imaging of tumor lesions and real-time intra-operative supervision.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Meios de Contraste , Corantes Fluorescentes , Metais Terras Raras , Nanopartículas , Animais , Linhagem Celular Tumoral , Meios de Contraste/química , Meios de Contraste/farmacocinética , Feminino , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacocinética , Fígado/metabolismo , Imageamento por Ressonância Magnética , Metais Terras Raras/química , Metais Terras Raras/farmacocinética , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/metabolismo , Imagem Óptica , Espectroscopia de Luz Próxima ao Infravermelho
5.
Chem Res Toxicol ; 32(7): 1357-1366, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31251039

RESUMO

Antibacterial agents are an important tool in the prevention of bacterial infections. Inorganic materials are attractive due to their high stability under a variety of conditions compared to organic antibacterial agents. Herein tungsten oxide nanodots (WO3-x), synthesized by a simple one-pot synthetic approach, were found to exhibit strong antibacterial capabilities. The analyses with colony-forming units (CFU) showed an excellent antibacterial activity of WO3-x against both Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) strains. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images revealed clear damages to the bacterial cell membranes, which was further confirmed by molecular dynamics simulations. Additionally, exposure to simulated sunlight was found to further increase the germicidal activity of WO3-x nanodots, a 30 min exposure to sunlight combined with 50 µg/mL WO3-x nanodots showed a 70% decrease in E. coli viability compared to without exposure. Electron spin resonance spectroscopy (ESR) was used to elucidate the underlying mechanism of this photocatalytic activity through the generation of hydroxyl radical species. The cell counting kit-8 (CCK-8) and the live/dead assay were further employed to evaluate the cytotoxicity of WO3-x nanodots on eukaryotic cells, which demonstrated their general biocompatibility. In summary, our results suggest WO3-x nanodots have considerable potential in antibacterial applications, while also being biocompatible at large.


Assuntos
Antibacterianos/farmacologia , Óxidos/farmacologia , Pontos Quânticos/química , Tungstênio/farmacologia , Antibacterianos/síntese química , Antibacterianos/toxicidade , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/efeitos da radiação , Humanos , Testes de Sensibilidade Microbiana , Óxidos/síntese química , Óxidos/toxicidade , Pontos Quânticos/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/efeitos da radiação , Tungstênio/toxicidade
6.
Small ; 14(52): e1803509, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30474237

RESUMO

The widespread use of nanomaterials, such as carbon based 2D nanomaterials, in biomedical applications, has been accompanied by a growing concern on their biocompatibility, and in particular, on how they may affect the integrity of cell membranes. Herein, the interactions between C2 N, a novel 2D nanomaterial, and human red blood cell membranes are explored using a combined experimental and theoretical approach. The experimental microscopies show that C2 N exerts a negligible hemolysis effect on the blood cells with a superior compatibility to their cell membranes, when compared with the control system, reduced graphene oxide (rGO), which is found to be highly hemolytic. The molecular dynamics simulations further reveal the underlying molecular mechanisms, which indicate that C2 N prefers to be adsorbed flat on the water-membrane interface. Interaction energy analyses demonstrate the crucial role of Coulombic contributions, originating from the unique electrostatic potential surface of C2 N, in preventing C2 N from penetrating into cell membranes. These findings indicate a high compatibility of C2 N with cell membranes, which may provide useful foundation for the future exploration of this 2D nanomaterial in related biomedical applications.


Assuntos
Membrana Eritrocítica/metabolismo , Grafite/química , Nanoestruturas/química , Humanos , Simulação de Dinâmica Molecular
7.
Small ; 13(3)2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27762498

RESUMO

Graphene and graphene-based nanomaterials are broadly used for various biomedical applications due to their unique physiochemical properties. However, how graphene-based nanomaterials interact with biological systems has not been thoroughly studied. This study shows that graphene oxide (GO) nanosheets retard A549 lung carcinoma cell migration through nanosheet-mediated disruption of intracellular actin filaments. After GO nanosheets treatment, A549 cells display slower migration and the structure of the intracellular actin filaments is dramatically changed. It is found that GO nanosheets are capable of absorbing large amount of actin and changing the secondary structures of actin monomers. Large-scale all-atom molecular dynamics simulations further reveal the interactions between GO nanosheets and actin filaments at molecular details. GO nanosheets can insert into the interstrand gap of actin tetramer (helical repeating unit of actin filament) and cause the separation of the tetramer which eventually leads to the disruption of actin filaments. These findings offer a novel mechanism of GO nanosheet induced biophysical responses and provide more insights into their potential for biomedical applications.


Assuntos
Citoesqueleto de Actina/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Grafite/farmacologia , Óxidos/farmacologia , Células A549 , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Morte Celular/efeitos dos fármacos , Grafite/química , Humanos , Ligação de Hidrogênio , Simulação de Dinâmica Molecular , Óxidos/química
8.
Neurol Res ; 46(6): 538-543, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38561007

RESUMO

BACKGROUND: Enterprise stent was approved for the treatment of wide-necked intracranial aneurysms. However, it has been widely used in the endovascular treatment of intracranial artery stenosis, which is still controversial. The purpose of this study was to evaluate the safety and efficiency of the Enterprise stent in the endovascular treatment of intracranial artery stenosis disease. METHODS: We conducted a retrospective case series of 107 patients with intracranial artery stenosis who received Enterprise stent implantation at Nanjing Drum Tower Hospital from January 2020 to December 2022. The rates of recanalization, perioperative complications, in-stent restenosis at 3-12 months and stroke recurrence were assessed for endovascular treatment. RESULTS: A total of 107 individuals were included in this study, 88 were followed up, and 19 (17.8%) patients were lost to follow-up. The operation success rate was 100%, During the procedure,4(3.7%)patients had vasospasm, and 2(1.9%) patients showed symptomatic bleeding. The overall perioperative complication rate was 5.6%, including 2.8% distal artery embolism, 0.9% in-stent thrombosis, and 1.9% symptomatic bleeding. 88 (82.2%) patients were followed up from 3 to 12 months, of whom 12 (13.6%) had in-stent restenosis, 4 (4.7%) recurrent strokes and 2 died of pulmonary infection caused by COVID-19. Patients were divided into 3 groups according to the cerebral artery, including the middle cerebral artery group, internal carotid artery group, and vertebrobasilar artery group. CONCLUSIONS: In this study, the placement of the Enterprise stent in patients with symptomatic non-acute intracranial stenosis was successful. However, the occurrence of periprocedural and long-term complications after stenting remains of high concern.


Assuntos
Procedimentos Endovasculares , Stents , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Stents/efeitos adversos , Estudos Retrospectivos , Procedimentos Endovasculares/métodos , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Idoso , Adulto , Resultado do Tratamento , Constrição Patológica , Doenças Arteriais Intracranianas/cirurgia
9.
Adv Healthc Mater ; : e2400830, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38857527

RESUMO

Compromises between enhanced on-targeting reactivity and precise real-time monitoring in the tumor microenvironment (TME) are the main roadblocks for catalytic cancer therapy. The hallmark of a high level of hydrogen peroxide (H2O2) and acidic extracellular environment of the hypoxia solid tumor can underpin therapeutic and tracking performance. Herein, this work provides an activatable wintersweet-like nanohybrid consisting of titanium (Ti) doped cerium vanadate nanorods with the modification of polypyrrole (PPy) nanoparticles (CeVO4-Ti@PPy) for combinatorial therapies of breast carcinoma. The Ti dopants in the size-controllable CeVO4 nanorods lower the energy barrier (0.5 eV) of the rate-determining steps and elaborate peroxidase-like (POD-like) activities to improve the generation of toxic hydroxyl radical (·OH) according to the density functional theory (DFT) calculation. The multiple enzyme-like activities, including the intrinsic glutathione peroxidase (GPx) and catalase (CAT), achieve a record-high therapeutic efficiency. Coupling this oxidative stress with the photothermal effects of PPy enables enhanced catalytic tumor necrosis. The exterior PPy heterogeneous structure can be further doped with protons in the local acidic environment to intensify photoacoustic signals, allowing the non-invasive accurate tracking of tumors. The theranostic performance displayed negligible attenuated signals in near-infrared (NIR) windows. This organic-inorganic nanohybrid with a heterogeneous structure provides the potential to improve the overall outcomes of catalytic therapy.

10.
Nanoscale Adv ; 5(16): 4240-4249, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37560436

RESUMO

The high mortality of breast cancer is closely related to lymph node (LN) metastasis. Sentinel LNs (SLNs) are the first station where tumor cells metastasize through the lymphatic system. As such, achieving precise diagnosis of the early metastatic status of SLNs during surgery is of paramount importance for precision therapy of breast cancer. While invasive SLNs biopsy is the gold standard for evaluating the status of SLNs, its use is often time-consuming and may increase the risk of operation. It is still challenging to develop a means for rapid SLN metastasis diagnosis. Herein, NaGdF4:5%Nd@NaLuF4 rare earth nanoparticles (Gd:Nd-RENPs) with near-infrared-II (NIR-II) fluorescence and magnetic resonance imaging (MRI) properties were fabricated. With the nanoprobe, metastatic SLNs and lymph vessels (LVs) rapidly brighten and can be observed by the NIR-II imaging system, which is totally different from normal LNs and LVs. The remarkable contrast observed via NIR-II imaging serves to swiftly delineate metastatic SLNs from normal ones, subsequently guiding precise surgical resection of metastatic LNs in just 10 minutes. Furthermore, the consistency between the results obtained via MRI and NIR-II imaging further validates the dependability of this nanoprobe as a diagnostic tool for metastatic SLNs. Additionally, the Gd:Nd-RENPs exhibited good biocompatibility in vitro and in vivo. In this study, we demonstrated the advantages and prospects of NIR-II imaging for intraoperative early SLN metastasis assessment and shed light on the potential of the dual-modal Gd:Nd-RENPs as a nanoprobe.

11.
ACS Nano ; 17(8): 7109-7134, 2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-37036400

RESUMO

Lesion areas are distinguished from normal tissues surrounding them by distinct physiological characteristics. These features serve as biological hallmarks with which targeted biomedical imaging of the lesion sites can be achieved. Although tremendous efforts have been devoted to providing smart imaging probes with the capability of visualizing the physiological hallmarks at the molecular level, the majority of them are merely able to derive anatomical information from the tissues of interest, and thus are not suitable for taking part in in vivo quantification of the biomarkers. Recent advances in chemical construction of advanced ratiometric nanoprobes (RNPs) have enabled a horizon for quantitatively monitoring the biological abnormalities in vivo. In contrast to the conventional probes whose dependency of output on single-signal profiles restricts them from taking part in quantitative practices, RNPs are designed to provide information in two channels, affording a self-calibration opportunity to exclude the analyte-independent factors from the outputs and address the issue. Most of the conventional RNPs have encountered several challenges regarding the reliability and sufficiency of the obtained data for high-performance imaging. In this Review, we have summarized the recent progresses in developing highly advanced RNPs with the capabilities of deriving maximized information from the lesion areas of interest as well as adapting themselves to the complex biological systems in order to minimize microenvironmental-induced falsified signals. To provide a better outlook on the current advanced RNPs, nanoprobes based on optical, photoacoustic, and magnetic resonance imaging modalities for visualizing a wide range of analytes such as pH, reactive species, and different derivations of amino acids have been included. Furthermore, the physicochemical properties of the RNPs, the major constituents of the nanosystems and the analyte recognition mechanisms have been introduced. Moreover, the alterations in the values of the ratiometric signal in response to the analyte of interest as well as the time at which the highest value is achieved, have been included for most of RNPs discussed in this Review. Finally, the challenges as well as future perspectives in the field are discussed.


Assuntos
Aminoácidos , Imageamento por Ressonância Magnética , Reprodutibilidade dos Testes
12.
Ann Nucl Med ; 36(1): 1-14, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34727331

RESUMO

With a 5-year overall survival of approximately 20%, lung cancer has always been the number one cancer-specific killer all over the world. As a fusion of positron emission computed tomography (PET) and computed tomography (CT), PET/CT has revolutionized cancer imaging over the past 20 years. In this review, we focused on the optimization of the function of 18F-flurodeoxyglucose (FDG)-PET/CT in diagnosis, prognostic prediction and therapy management of lung cancers by computer programs. FDG-PET/CT has demonstrated a surprising role in development of therapeutic biomarkers, prediction of therapeutic responses and long-term survival, which could be conducive to solving existing dilemmas. Meanwhile, novel tracers and optimized procedures are also developed to control the quality and improve the effect of PET/CT. With the continuous development of some new imaging agents and their clinical applications, application value of PET/CT has broad prospects in this area.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
13.
ACS Appl Mater Interfaces ; 14(26): 30306-30314, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35748354

RESUMO

With the rapid development of carbon-based two-dimensional nanomaterials in biomedical applications, growing concern has emerged regarding their biocompatibility and especially their interactions with cell membranes. Our experimental studies found that the oxidation state, as one of the most important chemical parameters of graphene derivatives, regulates the hemolysis effect on human red blood cells in a nonmonotonic manner. Scanning electron microscopy and optical microscopy observations suggested that graphene oxides with medium oxygen content have the most serious destructive effects on the cell membranes. Molecular dynamics simulations and potential of mean force calculations revealed that, on the one hand, with the decrease in the surface oxygenated groups, more sp2 carbon area of graphene-based materials will be exposed, playing a facilitating role in the damage of cell membranes; on the other hand, fewer oxygenated groups also lead to the accumulation of graphene-based nanosheets in solutions. The formation of the multilayer structure of graphene-based nanosheets reduces the exposed sp2 carbon area, prevents the collective extraction of lipid molecules, and eventually results in a weakened extraction effect on cell membranes. Together, these factors generate a nonmonotonic relationship between the oxidation state of graphene oxides and their destructive effects on cell membranes.


Assuntos
Grafite , Carbono/análise , Membrana Celular/química , Grafite/química , Humanos , Oxirredução , Óxidos/química
14.
Sci Total Environ ; 805: 150302, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34536880

RESUMO

The risk of graphene oxide (GO) exposure to various species has been greatly amplified in recent years due to its booming production and applications in various fields. However, a deep understanding of the GO biosafety lags its wide applications. Herein, we used W1118 flies as a model organism to study GO toxicity at relatively low concentrations. We found that GO exposure led to remarkable weight loss, delayed development, retarded motion, and shortened lifespan of these flies. On the other hand, the GO influence on their sex ratio and the total number of pupae and adults were insignificant. The toxicological effect of GO was shown to be related to its serious compromise of the nutrient absorption in flies due to the severe damages in midguts. These damages were then attributed to the excessive accumulation of reactive oxygen species (ROS), which triggers the oxidative stress. These findings reveal the underlying mechanisms of GO biotoxicities in fruit flies, which might provide a useful reference to assess the risks of these newly invented nanomaterials likely never encountered by various species before.


Assuntos
Dípteros , Grafite , Animais , Grafite/toxicidade , Óxidos/toxicidade , Espécies Reativas de Oxigênio
15.
Biomed Pharmacother ; 146: 112496, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34959117

RESUMO

Intestinal injury is one of the major side effects that are induced by medical radiation exposure, and has limited effective therapies. In this study, we investigated the beneficial effects of sanguinarine (SAN) on intestinal injury induced by ionizing radiation (IR) both in vitro and in vivo. Mice were exposed to whole abdominal irradiation (WAI) to mimic clinical scenarios. SAN was injected intraperitoneally to mitigate IR-induced injury. Histological examination was performed to assess the tissue injuries of the spleen and small intestine. A small intestinal epithelial cell line-6 (IEC-6) was analyzed for its viability and apoptosis in vitro under different treatments. Inflammation-related pathways and serum inflammatory cytokines were detected via Western blot analysis and ELISA, respectively. High-throughput sequencing was used to characterize the gut microbiota profile. High-performance liquid chromatography was performed to assess short-chain fatty acid contents in the colon. In vitro, SAN pretreatment protected cell viability and reduced apoptosis in IEC-6 cells. In vivo, SAN pretreatment protected immune organs, alleviated intestinal injury, and promoted intestinal recovery. SAN also reduced the levels of inflammatory cytokines, suppressed high mobility group box 1 (HMGB1)/ Toll-like receptor 4 (TLR4) pathway activation, and modulated gut microbiota composition. Our findings demonstrate that the beneficial properties of SAN alleviated intestinal radiation injury. Thus, SAN represents a therapeutic option for protecting against IR-induced intestinal injury in preclinical settings.


Assuntos
Benzofenantridinas/farmacologia , Intestino Delgado/efeitos dos fármacos , Isoquinolinas/farmacologia , Lesões Experimentais por Radiação/prevenção & controle , Baço/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação para Baixo , Ácidos Graxos Voláteis , Microbioma Gastrointestinal/efeitos dos fármacos , Proteína HMGB1/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Injeções Intraperitoneais , Intestino Delgado/patologia , Intestino Delgado/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Lesões Experimentais por Radiação/patologia , Radiação Ionizante , Transdução de Sinais/efeitos dos fármacos , Baço/patologia , Baço/efeitos da radiação , Receptor 4 Toll-Like/efeitos dos fármacos
16.
Colloids Surf B Biointerfaces ; 203: 111765, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33866278

RESUMO

Boron nitride (BN) nanosheets have emerged as promising nanomaterials in a wide range of biomedical applications. Despite extensive studies on these bio-nano interfacial systems, the underlying molecular mechanisms remain elusive. In this study, we used hemolysis assays and morphology observations to demonstrate for the first time that BN nanosheets can cause damages to the red-blood-cell membranes, leading to significant hemolysis. Further molecular dynamics simulations revealed that BN nanosheets can penetrate into the cell membrane and also extract considerable amount of phospholipid molecules directly from the lipid bilayer. The potential of mean force calculations then showed that their penetration effect was thermodynamically favorable due to the strong attractive van der Waals interactions between BN nanosheets and phospholipids. Overall, these findings provided valuable insights into the interaction of BN nanosheets with cell membranes at the atomic level, which can help future de novo design of BN-based nanodevices with better biocompatibility.


Assuntos
Hemólise , Nanoestruturas , Compostos de Boro , Humanos , Bicamadas Lipídicas
17.
Dose Response ; 19(1): 15593258211003798, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33867894

RESUMO

PURPOSE: The main objective is to investigate the protective effect of camel milk (CM) on radiation-induced intestinal injury. METHODS: The C57BL/6 J mice in 2 experiments were assigned into control group (Con), irradiation group (IR), and CM+irradiation group (CM+IR). After receiving the CM via gavage for 14 days, the mice in the first experiment were exposed to 6 Gy X-ray whole body irradiation, and survival rate was compared among the groups. Mice in the second experiment were exposed to 4 Gy irradiation and sacrificed at day 7. The small intestines were collected to examine the histopathological changes and to determine the anti-oxidative index and HMGB1/TLR4 inflammatory pathway. Fasting blood was used to measure serum pro-inflammatory factors. RESULTS: Compared with the IR group, the survival time was prolonged, and survival rate was increased in the CM+IR group. CM increased levels of SOD and GSH and decreased MDA in the jejunum. Furthermore, intestinal protein expression of HMGB1/TLR4 pathway (TLR4, NF-κB, and HMGB1) was up-regulated by CM intervention. CM decreased the serum levels of TNF-α and IL-1ß and increased IL-10 level. CONCLUSIONS: CM extended the survival time and had a protective effect against radiation-induced jejunum injury by regulation of antioxidant capacity and HMGB1/TLR4/NF-κB/MyD88 inflammatory signaling pathway.

18.
Nanoscale ; 12(17): 9430-9439, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32313912

RESUMO

Phosphorene, a monolayer of black phosphorus, has emerged as one of the most promising two-dimensional (2D) nanomaterials for various applications in the post-graphene-discovery period due to its highly anisotropic structure and novel properties. In order to apply phosphorene in biomedical fields, it is crucial to understand how it interacts with biomolecules. Herein, we use both molecular dynamics (MD) simulations and experimental techniques to investigate the interactions of phosphorene with a dsDNA segment. Our results reveal that dsDNA can form a stable binding on the phosphorene surface through the terminal base pairs and adopt an upright orientation regardless of its initial configurations. Moreover, the binding strength of dsDNA with phosphorene is found to be mild and does not cause significant distortion in the internal structure of dsDNA. This phenomenon is attributed to the weaker dispersion interaction between dsDNA and phosphorene. Further analysis of the free energy profile calculated by the umbrella sampling technique suggests that the puckered surface morphology significantly reduces the adsorption free energy of DNA bases to phosphorene. Compared to graphene, phosphorene is found to show a milder attraction to DNA, which is confirmed by our electrophoresis experiments. We believe that these findings provide valuable insight into the molecular interactions between phosphorene and dsDNA which may prompt further investigation of phosphorene for future biomedical applications.


Assuntos
DNA/química , Nanoestruturas/química , Fósforo/química , Adsorção , Pareamento de Bases , Eletroforese em Gel de Ágar , Entropia , Grafite/química , Simulação de Dinâmica Molecular , Propriedades de Superfície , Água/química
19.
ACS Appl Mater Interfaces ; 12(39): 43398-43407, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33003260

RESUMO

X-ray-responsive nanocarriers for anticancer drug delivery have shown great promise for enhancing the efficacy of chemoradiotherapy. A critical challenge remains for development of such radiation-controlled drug delivery systems (DDSs), which is to minimize the required X-ray dose for triggering the cargo release. Herein, we design and fabricate an effective DDS based on diselenide block copolymers (as nanocarrier), which can be triggered to release their cargo with a reduced radiation dose of 2 Gy due to their sensitivity to both X-ray and the high level of reactive oxygen species (ROS) in the microenvironment of cancer cells. The underlying molecular mechanism is further illustrated by proton nuclear magnetic resonance (1H NMR) experiments and density functional theory (DFT) calculations. In vivo experiments on tumor-bearing mice validated that the loaded drugs are effectively delivered to the tumor site and exert remarkable antitumor effects (minimum tumor volume/weight) along with X-ray. Furthermore, the diselenide nanocarriers exhibit no noticeable cytotoxicity. These findings provide new insights for the de novo design of radiation-controlled DDSs for cancer chemoradiotherapy.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Compostos de Selênio/química , Animais , Antibióticos Antineoplásicos/síntese química , Antibióticos Antineoplásicos/química , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Teoria da Densidade Funcional , Doxorrubicina/síntese química , Doxorrubicina/química , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Imagem Óptica , Tamanho da Partícula , Compostos de Selênio/síntese química , Propriedades de Superfície , Raios X
20.
Dose Response ; 18(3): 1559325820956783, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973418

RESUMO

PURPOSE AND METHODS: To investigate the doses of total body (TBI) and whole abdominal irradiation (WAI) induced lethal intestinal injury, healthy C57BL/6 J mice were divided randomly into 7 groups: control group; 6, 7, and 8 Gy TBI groups; and 5, 10, and 15 Gy WAI groups. The survival length, general conditions, body weight, daily food and water intake of the mice and the histopathological changes of small intestine were observed. RESULTS: Lethal injury among C57BL/6 J mice was caused by ≥6 Gy TBI and 15 Gy WAI. Their body weight and food intake decreased, the structure of their small intestinal villi was destroyed, and the number of surviving crypts per circumference of the jejunum decreased in ≥6 Gy TBI groups and 15 Gy WAI group. The mice in the 10 Gy WAI group significantly lost weight within 5 days but recovered slowly thereafter. They also had poor appetite and reversibly damaged intestinal mucosa. CONCLUSIONS: Nonlethal intestinal injury could be induced by 10 Gy WAI, whereas lethal intestinal injury could be triggered by ≥6 Gy TBI and >15 Gy WAI in mice. Our results provided a basis for establishing radiation-induced intestinal injury models with C57BL/6 J mice.

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