RESUMO
The in vivo functions of SerpinB2 in tumor cells and tumor-associated macrophages (TAMs) during breast cancer development and metastasis remain elusive. SerpinB2-deficient MMTV-PyMT mice (PyMTSB2-/-) were previously produced to explore the biological roles of SerpinB2 in breast cancer. Compared with MMTV-PyMT wild-type (PyMTWT) mice, PyMTSB2-/- mice showed delayed tumor progression and reduced CK8 + tumor cell dissemination to lymph nodes. RNA-Seq data revealed significantly enriched genes associated with inflammatory responses, especially upregulated M1 and downregulated M2 macrophage marker genes in PyMTSB2-/- tumors. Decreased CD206+M2 and increased NOS2+M1 markers were detected in the primary tumors and metastatic lymph nodes of PyMTSB2-/- mice. In an in vitro study, SerpinB2 knockdown decreased the sphere formation and migration of MDA-MB-231 cells and suppressed protumorigenic M2 polarization of RAW264.7 cells. The combination of low SerpinB2, high NOS2, and low CD206 expression was favorable for survival in patients with breast cancer, as assessed in the BreastMark dataset. Our study demonstrates that SerpinB2 deficiency delays mammary tumor development and metastasis in PyMTWT mice, along with reduced sphere formation and migration abilities of tumor cells and decreased macrophage protumorigenic polarization.
Assuntos
Neoplasias da Mama , Inibidor 2 de Ativador de Plasminogênio , Animais , Feminino , Humanos , Camundongos , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Macrófagos/metabolismo , Neoplasias Mamárias Experimentais/patologia , Neoplasias Mamárias Experimentais/genética , Camundongos Knockout , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Inibidor 2 de Ativador de Plasminogênio/genética , Inibidor 2 de Ativador de Plasminogênio/metabolismo , Inibidor 2 de Ativador de Plasminogênio/deficiência , Células RAW 264.7 , Macrófagos Associados a Tumor/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismoRESUMO
Thymocyte selection-associated high-mobility group box (TOX) is a transcription factor that is crucial for T cell exhaustion during chronic antigenic stimulation, but its role in inflammation is poorly understood. Here, we report that TOX extracellularly mediates drastic inflammation upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by binding to the cell surface receptor for advanced glycation end-products (RAGE). In various diseases, including COVID-19, TOX release was highly detectable in association with disease severity, contributing to lung fibroproliferative acute respiratory distress syndrome (ARDS). Recombinant TOX-induced blood vessel rupture, similar to a clinical signature in patients experiencing a cytokine storm, further exacerbating respiratory function impairment. In contrast, disruption of TOX function by a neutralizing antibody and genetic removal of RAGE diminished TOX-mediated deleterious effects. Altogether, our results suggest an insight into TOX function as an inflammatory mediator and propose the TOX-RAGE axis as a potential target for treating severe patients with pulmonary infection and mitigating lung fibroproliferative ARDS.
Assuntos
COVID-19 , Receptor para Produtos Finais de Glicação Avançada , SARS-CoV-2 , Humanos , Receptor para Produtos Finais de Glicação Avançada/metabolismo , COVID-19/imunologia , COVID-19/metabolismo , COVID-19/patologia , COVID-19/complicações , COVID-19/virologia , Animais , Camundongos , Inflamação/metabolismo , Inflamação/patologia , Síndrome do Desconforto Respiratório/imunologia , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/patologia , Síndrome do Desconforto Respiratório/virologia , Lesão Pulmonar/imunologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Proteínas de Grupo de Alta Mobilidade/metabolismo , Proteínas de Grupo de Alta Mobilidade/genética , Masculino , Pulmão/patologia , Pulmão/metabolismo , Pulmão/imunologia , FemininoRESUMO
Background: Osteoarthritis (OA), the most prevalent form of arthritis, is a degenerative joint disease marked by the progressive deterioration of articular cartilage, leading to clinical manifestations such as joint pain. Objective: This study investigated the effects of Curcuma longa L. extract (CL) containing curcumin, demethoxycurcumin, and bisdemethoxycurcumin on monosodium iodoacetate (MIA)-induced OA rats. Design: Sprague-Dawley rats with MIA-induced OA received CL supplementation at doses of 5, 25, and 40 mg/kg body weight. Results: CL extract administration suppressed mineralisation parameters and morphological modifications and decreased arachidonate5-lipoxygenase and leukotriene B4 levels in articular cartilage. Additionally, it decreased serum prostaglandin E2, NO, and glycosaminoglycanlevels as well as the protein expression of phosphorylated inhibitor kappa B-alpha, phosphorylated p65, cyclooxygenase-2, and inducible nitric oxide synthase in the cartilage of MIA-injected rats. Furthermore, it also reduced matrix metalloproteinases and elevated SMAD family member 3 phosphorylation, tissue inhibitor of metalloproteinases, aggrecan, collagen type I, and collagen type II levels in the articular cartilage of MIA-induced OA rats. Conclusions: This study's findings suggest that CL supplementation helps prevent OA development and is an effective therapy for OA.
RESUMO
Wearable 2.0 research has been conducted on the manufacture of smart fitness wear that collects bio-signals through the wearing of a textile-based electrode. Among them, the electromyography (EMG) suit measures the electrical signals generated by the muscles to check their activity, such as contraction and relaxation. General gel-type electrodes have been reported to cause skin diseases due to an uncomfortable feel and skin irritation when attached to the skin for a long time. Dry electrodes of various materials are being developed to solve this problem. Previous research has reported EMG detectio performance and conducted economic comparisons according to the size and shape of the embroidery electrode. On the other hand, these embroidery electrodes still have foreign body sensations. In this study, a moss sEMG electrode was produced with various shapes (W3 and WF) and loop lengths (1-5 mm). The optimized conditions of the embroidery-based electrodes were derived and analyzed with the tactile comfort factors and sensing performances. As the loop length of the electrode increased, MIU and Qmax increased, but the SMD decreased due to the free movement of the threads constituting the loop. Impedance and sEMG detection performance showed different trends depending on the electrode type.
Assuntos
Eletricidade , Têxteis , Eletromiografia/métodos , Impedância Elétrica , EletrodosRESUMO
Ag/AgCl hydrogel electrodes, which are wet electrodes, are generally used to acquire bio-signals non-invasively. Research concerning dry electrodes is ongoing due to the following limitations of wet electrodes: (1) skin irritation and disease when attached for a long time; (2) poor adhesion due to sweat; and (3) considerable cost due to disposable use. Accordingly, electrodes in film, embroidery, and knit forms were manufactured from conductive sheets and conductive yarns, which are typical textile-type dry electrode materials, using different manufacturing methods and conditions. The prepared electrodes were conducted to measure the morphology, surface resistance, skin-electrode impedance, EMG signal acquisition, and analysis. The conductive sheet type electrode exhibited a similar skin-impedance, noise, and muscle activation signal amplitude to the Ag/AgCl gel electrode due to the excellent adhesion and shape stabilization. Embroidery electrodes were manufactured based on two-dimension lock stitch (Em_LS) and three-dimension moss-stitch (Em_MS). More stable EMG signal acquisition than Em_LS was possible when manufactured with Em_MS. The knit electrode was manufactured with the typical structures of plain, purl, and interlock. Although it was possible to acquire EMG signals, considerable noise was generated as the shape and size of the electrodes were changed due to the stretch characteristics of the knit structure. Finally, the applicability of the textile-type dry electrode was confirmed by combining it with a wearable device. More stable and accurate EMG signal acquirement will be possible through more precise parameter control in the future.
RESUMO
The interest in wearable devices has expanded to measurement devices for building IoT-based mobile healthcare systems and sensing bio-signal data through clothing. Surface electromyography, called sEMG, is one of the most popular bio-signals that can be applied to health monitoring systems. In general, gel-based (Ag/AgCl) electrodes are mainly used, but there are problems, such as skin irritation due to long-time wearing, deterioration of adhesion to the skin due to moisture or sweat, and low applicability to clothes. Hence, research on dry electrodes as a replacement is increasing. Accordingly, in this study, a textile-based electrode was produced with a range of electrode shapes, and areas were embroidered with conductive yarn using an embroidery technique in the clothing manufacturing process. The electrode was applied to EMG smart clothing for fitness, and the EMG signal detection performance was analyzed. The electrode shape was manufactured using the circle and wave type. The wave-type electrode was more morphologically stable than the circle-type electrode by up to 30% strain, and the electrode shape was maintained as the embroidered area increased. Skin-electrode impedance analysis confirmed that the embroidered area with conductive yarn affected the skin contact area, and the impedance decreased with increasing area. For sEMG performance analysis, the rectus femoris was selected as a target muscle, and the sEMG parameters were analyzed. The wave-type sample showed higher EMG signal strength than the circle-type. In particular, the electrode with three lines showed better performance than the fill-type electrode. These performances operated without noise, even with a commercial device. Therefore, it is expected to be applicable to the manufacture of electromyography smart clothing based on embroidered electrodes in the future.
Assuntos
Materiais Inteligentes , Dispositivos Eletrônicos Vestíveis , Eletrodos , Eletromiografia/métodos , TêxteisRESUMO
Severe infectious diseases, such as coronavirus disease 2019 (COVID-19), can induce hypercytokinemia and multiple organ failure. In spite of the growing demand for peptide therapeutics against infectious diseases, current small molecule-based strategies still require frequent administration due to limited half-life and enzymatic digestion in blood. To overcome this challenge, a strategy to continuously express multi-level therapeutic peptide drugs on the surface of immune cells, is established. Here, chimeric T cells stably expressing therapeutic peptides are presented for treatment of severe infectious diseases. Using lentiviral system, T cells are engineered to express multi-level therapeutic peptides with matrix metallopeptidases- (MMP-) and tumor necrosis factor alpha converting enzyme- (TACE-) responsive cleavage sites on the surface. The enzymatic cleavage releases γ-carboxyglutamic acid of protein C (PC-Gla) domain and thrombin receptor agonist peptide (TRAP), which activate endothelial protein C receptor (EPCR) and protease-activated receptor-1 (PAR-1), respectively. These chimeric T cells prevent vascular damage in tissue-engineered blood vessel and suppress hypercytokinemia and lung tissue damages in vivo, demonstrating promise for use of engineered T cells against sepsis and other infectious-related diseases.
Assuntos
COVID-19 , Doenças Transmissíveis , Antígenos CD/metabolismo , Antígenos CD/farmacologia , Síndrome da Liberação de Citocina , Células Endoteliais/metabolismo , Humanos , Peptídeos/metabolismo , Receptor PAR-1/metabolismo , Receptores de Superfície Celular/metabolismo , Linfócitos T/metabolismoRESUMO
This study aimed to manufacture PAN-based conductive yarn using a wet-spinning process. Two types of carbon nanomaterials, multiwall carbon nanotubes (MWCNT) and carbon nanofiber (CNF), were used alone or in a mixture. First, to derive the optimal composite solution condition for the wet spinning process, a composite solution was prepared with carbon nanomaterials of the same total mass weight (%) and three types of mechanical stirring were performed: mechanical stirring, ultra-sonication, and ball milling. A ball milling process was finally selected by analyzing the viscosity. Based on the above results, 8, 16, 24, and 32 wt% carbon nanomaterial/PAN composite solutions were prepared to produce wet spinning-based composite films before preparing a conductive yarn, and their physical and electrical properties were examined. By measuring the viscosity of the composite solution and the surface resistance of the composite film according to the type and content of carbon nanomaterials, a suitable range of viscosity was found from 103 cP to 105 cP, and the electrical percolation threshold was from 16 wt% carbon nanomaterial/PAN, which showed a surface resistance of 106 Ω/sq or less. Wet spinning was possible with a PAN-based composite solution with a high content of carbon nanomaterials. The crystallinity, crystal orientation, tenacity, and thermal properties were improved when CNF was added up to 24 wt%. On the other hand, the properties deteriorated when CNTs were added alone due to aggregation. Mixing CNT and CNF resulted in poorer properties than with CNF alone, but superior properties to CNT alone. In particular, the electrical properties after incorporating 8 wt% CNT/16 wt% CNF into the PAN, 106 Ω/cm was similar to the PAN-based conductive yarn containing 32 wt% CNF. Therefore, this yarn is expected to be applicable to various smart textiles and wearable devices because of its improved physical properties such as strength and conductivity.
RESUMO
PURPOSE: The breast cancer susceptibility gene, BRCA1, is involved in normal development and carcinogenesis of mammary glands. Here, we aimed to evaluate the relationship between histological findings of mammary gland development and breast cancer risk in BRCA1 mutant mice. METHODS: Five BRCA1 mutant mice and five non-mutant FVB/NJ mice were used for each group of 1-month-old (pubertal), 3-month-old (fertile), and 8-month-old (menopausal) mice. In another experiment, 15 BRCA1 mutant mice were followed up to 8 months after birth and classified into tumor-bearing (11 mice) and tumor-free (4 mice) groups. Excised mammary gland tissues were stained with Carmine Alum, and the number of terminal end buds (or alveolar buds), branching density, and duct elongation were measured using image analysis programs. Differences between the two groups were assessed using paired t-test. RESULTS: One-month-old BRCA1 mutant mice showed a higher number of terminal end buds (23.8 ± 1.0 vs. 15.6 ± 0.8, p = 0.0002), branching density (11.7 ± 0.4 vs. 9.6 ± 0.5%, p = 0.0082), and duct elongation (9.7 ± 0.7 vs. 7.3 ± 0.4 mm, p = 0.0186) than controls. However, there was no difference between the 3- and 8-month-old groups. In BRCA1 mutant mice, the tumor-bearing group showed a significantly higher number of alveolar buds (142.7 ± 5.5 vs. 105.5 ± 5.4, p = 0.0008) and branching density (30.0 ± 1.0 vs. 24.1 ± 1.1%, p = 0.008) than the tumor-free group; however, duct elongation was not different (23.9 ± 0.6 vs. 23.6 ± 0.6 mm, p = 0.8099) between the groups. CONCLUSION: BRCA1 mutant mice exhibited early pubertal mammary gland development and delayed age-related mammary gland involution was associated with breast cancer. Our results may have clinical implications for predicting breast cancer risk and developing prevention strategies for BRCA1 mutation carriers.
RESUMO
To evaluate the electrical heating performance by auxetic pattern, re-entrant honeycomb (RE), chiral truss (CT), honeycomb (HN), and truss (TR), using graphene/PLA (Polylactic acid) filament, were manufactured by CFDM (conveyor fused deposition modelling) 3D printer. In addition, HN and TR, which was indicated to have an excellent electrical heating property, were selected to verify the feasibility of applying fabric heating elements. The result of morphology was that the number of struts constituting the unit cell and the connected points were TR < HN < CT < RE. It was also influenced by the surface resistivity and electrical heating performance. RE, which has the highest number of struts constituting the unit cell and the relative density, had the highest value of surface resistivity, and the lowest value was found in the opposite TR. In the electrical heating performance of samples, the heat distribution of RE was limited even when the applied voltage was increased. However, HN and TR were diffused throughout the sample. In addition, the surface temperature of RE, CT, HN, and TR was about 72.4 °C, 83.1 °C, 94.9 °C, and 85.9, respectively as applied at 30 V. When the HN and TR were printed on cotton fabric, the surface resistivity of HN/cotton and TR/cotton was about 103 Ω/sq, which showed conductive material. The results of electrical heating properties indicated that the heat distribution of HN/cotton showed only in the region where power was supplied, but the TR/cotton was gradually expanded and presented stable electric heating properties. When 30 V was applied, the surface temperature of both samples showed more than 80 °C, and the shape was maintained stably due to the high thermal conductivity of the cotton fabric. Therefore, this study ensured that HN and TR show excellent electrical heating performance among four types of auxetic patterns with continuity.
RESUMO
The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on a global scale urges prompt and effective countermeasures. Recently, a study has reported that coronavirus disease-19 (COVID-19), the disease caused by SARS-CoV-2 infection, is associated with a decrease in albumin level, an increase in NETosis, blood coagulation, and cytokine level. Here, we present drug-loaded albumin nanoparticles as a therapeutic agent to resolve the clinical outcomes observed in severe SARS-CoV-2 patients. PEGylated nanoparticle albumin-bound (PNAB) was used to promote prolonged bioactivity of steroidal ginsenoside saponins, PNAB-Rg6 and PNAB-Rgx365. Our data indicate that the application of PNAB-steroidal ginsenoside can effectively reduce histone H4 and NETosis-related factors in the plasma, and alleviate SREBP2-mediated systemic inflammation in the PBMCs of SARS-CoV-2 ICU patients. The engineered blood vessel model confirmed that these drugs are effective in suppressing blood clot formation and vascular inflammation. Moreover, the animal model experiment showed that these drugs are effective in promoting the survival rate by alleviating tissue damage and cytokine storm. Altogether, our findings suggest that these PNAB-steroidal ginsenoside drugs have potential applications in the treatment of symptoms associated with severe SARS-CoV-2 patients, such as coagulation and cytokine storm.
Assuntos
COVID-19 , Ginsenosídeos , Nanopartículas , Albuminas , Animais , Ginsenosídeos/farmacologia , Humanos , Polietilenoglicóis , SARS-CoV-2RESUMO
In response to the coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global efforts are focused on the development of new therapeutic interventions. For the treatment of COVID-19, selective lung-localizing strategies hold tremendous potential, as SARS-CoV-2 invades the lung via ACE2 receptors and causes severe pneumonia. Similarly, recent reports have shown the association of COVID-19 with decreased 25-hydroxycholesterol (25-HC) and increased cytokine levels. This mechanism, which involves the activation of inflammatory NF-κB- and SREBP2-mediated inflammasome signaling pathways, is believed to play a crucial role in COVID-19 pathogenesis, inducing acute respiratory distress syndrome (ARDS) and sepsis. To resolve those clinical conditions observed in severe SARS-CoV-2 patients, we report 25-HC and didodecyldimethylammonium bromide (DDAB) nanovesicles (25-HC@DDAB) as a COVID-19 drug candidate for the restoration of intracellular cholesterol level and suppression of cytokine storm. Our data demonstrate that 25-HC@DDAB can selectively accumulate the lung tissues and effectively downregulate NF-κB and SREBP2 signaling pathways in COVID-19 patient-derived PBMCs, reducing inflammatory cytokine levels. Altogether, our findings suggest that 25-HC@DDAB is a promising candidate for the treatment of symptoms associated with severe COVID-19 patients, such as decreased cholesterol level and cytokine storm.
RESUMO
Ischemic stroke remains a leading cause of disability worldwide, with limited treatment options available. This study investigates GABAC receptors as novel pharmacological targets for stroke recovery. The expression of ρ1 and ρ2 mRNA in mice were determined in peri-infarct tissue following photothrombotic motor cortex stroke. (R)-4-amino-cyclopent-1-enyl butylphosphinic acid (R)-4-ACPBPA and (S)-4-ACPBPA were assessed using 2-elecotrode voltage electrophysiology in Xenopus laevis oocytes. Stroke mice were treated for 4 weeks with either vehicle, the α5-selective negative allosteric modulator, L655,708, or the ρ1/2 antagonists, (R)-4-ACPBPA and (S)-4-ACPBPA respectively from 3 days post-stroke. Infarct size and expression levels of GAT3 and reactive astrogliosis were determined using histochemistry and immunohistochemistry respectively, and motor function was assessed using both the grid-walking and cylinder tasks. After stroke, significant increases in ρ1 and ρ2 mRNAs were observed on day 3, with ρ2 showing a further increase on day 7. (R)- and (S)-4-ACPBPA are both potent antagonists at ρ2 and only weak inhibitors of α5ß2γ2 receptors. Treatment with either L655,708, (S)-4-ACPBPA (ρ1/2 antagonist; 5 mM only), or (R)-4-ACPBPA (ρ2 antagonist; 2.5 and 5 mM) from 3 days after stroke resulted in a significant improvement in motor recovery on the grid-walking task, with L655,708 and (R)-4-ACPBPA also showing an improvement in the cylinder task. Infarct size was unaffected, and only (R)-4-ACPBPA significantly increased peri-infarct GAT3 expression and decreased the level of reactive astrogliosis. Importantly, inhibiting GABAC receptors affords significant improvement in motor function after stroke. Targeting the ρ-subunit could provide a novel delayed treatment option for stroke recovery.
RESUMO
In skeletal-muscle regeneration, it is critical to promote efferocytosis of immune cells and differentiation of satellite cells/postnatal muscle stem cells at the damaged sites. With the optimized poloxamer 407 composition gelled at body temperature, the drugs can be delivered locally. The purpose of this study is to develop a topical injection therapeutic agent for muscle regeneration, sarcopenia, and cachexia. Herein, we construct an injectable, in situ hydrogel system consisting of CD146, IGF-1, collagen I/III, and poloxamer 407, termed CIC gel. The secreted CD146 then binds to VEGFR2 on the muscle surface and effectively induces efferocytosis of neutrophils and macrophages. IGF-1 promotes satellite cell differentiation, and biocompatible collagen evades immune responses of the CIC gel. Consequently, these combined molecules activate muscle regeneration via autophagy and suppress muscle inflammation and apoptosis. Conclusively, we provide an applicable concept of the myogenesis-activating protein formulation, broadening the thermoreversible hydrogel to protein therapeutics for damaged muscle recovery.
Assuntos
Hidrogéis , Nanopartículas , Antígeno CD146/metabolismo , Colágeno/metabolismo , Hidrogéis/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Músculo Esquelético , Nanopartículas/uso terapêutico , Poloxâmero/farmacologia , CicatrizaçãoRESUMO
Antimony oxide (ATO) is used mainly as a flame retardant, but it is classified as a hazardous substance. Therefore, regulations on the use of antimony trioxide (ATO(3)) and antimony pentoxide (ATO(5)) in textile products are being developed. Accordingly, there is a need for alternative flame retardants. In this study, antimony tetroxide (ATO(4)), which has higher thermal stability and resistance to acids and alkalis than ATO(3) or ATO(5), was selected to assess its use as an alternative flame retardant. First, ATO(3) or ATO(4) were added to poly(acrylonitrile-co-vinylidene chloride) (PANVDC), and the film and wet-spun fiber were prepared. The PANVDC film with flame retardants was prepared to evaluate the flame retardancy and the mechanism of action of the flame retardants. Flame retardancy analysis showed that a limiting oxygen index of 31.2% was obtained when ATO(4) was added, which was higher than when ATO(3) was used. Subsequently, PANVDC fibers with antimony oxide were manufactured and showed improved mechanical and thermal properties when ATO(4) was used, compared to when ATO(3) was tested. In addition, migration analysis due to antimony in the fiber confirmed that the elution amount was below the acceptable standard when PANVDC fibers with ATO(4) were added. Therefore, based on these results, the flame-retardant and thermal properties of antimony tetroxide were superior to antimony trioxide, and it was confirmed that ATO(4) could be used as an alternative flame retardant to ATO(3).
RESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus not previously identified in humans. Globally, the number of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) have risen dramatically. Currently, there are no FDA-approved antiviral drugs and there is an urgency to develop treatment strategies that can effectively suppress SARS-CoV-2-mediated cytokine storms, acute respiratory distress syndrome (ARDS), and sepsis. As symptoms progress in patients with SARS-CoV-2 sepsis, elevated amounts of cell-free DNA (cfDNA) are produced, which in turn induce multiple organ failure in these patients. Furthermore, plasma levels of DNase-1 are markedly reduced in SARS-CoV-2 sepsis patients. In this study, we generated recombinant DNase-1-coated polydopamine-poly(ethylene glycol) nanoparticulates (named long-acting DNase-1), and hypothesized that exogenous administration of long-acting DNase-1 may suppress SARS-CoV-2-mediated neutrophil activities and the cytokine storm. Our findings suggest that exogenously administered long-acting nanoparticulate DNase-1 can effectively reduce cfDNA levels and neutrophil activities and may be used as a potential therapeutic intervention for life-threatening SARS-CoV-2-mediated illnesses.
Assuntos
COVID-19/complicações , Síndrome da Liberação de Citocina/tratamento farmacológico , DNA/sangue , Desoxirribonuclease I/uso terapêutico , Portadores de Fármacos/administração & dosagem , Nanopartículas/administração & dosagem , Neutrófilos/efeitos dos fármacos , SARS-CoV-2 , Sepse/tratamento farmacológico , Animais , COVID-19/sangue , COVID-19/imunologia , Síndrome da Liberação de Citocina/etiologia , Desoxirribonuclease I/administração & dosagem , Dexametasona/uso terapêutico , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Armadilhas Extracelulares/efeitos dos fármacos , Humanos , Indóis , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/prevenção & controle , NF-kappa B/sangue , Neutrófilos/enzimologia , Peroxidase/sangue , Polietilenoglicóis , Poliglactina 910 , Polímeros , Sepse/etiologia , Sepse/imunologiaRESUMO
Chondroitin sulfate-hybridized zein nanoparticles (zein/CS NPs) were developed for targeted delivery of docetaxel, which exhibited mean diameters of 157.8 ± 3.6 nm and docetaxel encapsulation efficiency of 64.2 ± 1.9 %. Docetaxel was released from the NPs in a sustained manner (â¼72 h), following first-order kinetics. The zein/CS NPs showed improved colloidal stability, maintaining the initial size in serum for 12 h. The pre-treatment of CS reduced the uptake efficiency of the NPs by 23 % in PC-3 cells, suggesting the involvement of CD44-mediated uptake mechanism. The NPs showed 2.79-fold lower IC50 values than free docetaxel. Enhanced tumor accumulation of the NPs was confirmed in PC-3 xenograft mice by near-infrared fluorescence imaging (35.3-fold, versus free Cy5.5). The NPs exhibited improved pharmacokinetic properties (9.5-fold longer terminal half-life, versus free docetaxel) and anti-tumor efficacy comparable to Taxotere with negligible systemic toxicity, suggesting zein/CS NPs could be a promising nanoplatform for targeted cancer therapy.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/administração & dosagem , Sulfatos de Condroitina/química , Docetaxel/administração & dosagem , Portadores de Fármacos/química , Nanopartículas/química , Neoplasias da Próstata/tratamento farmacológico , Zeína/química , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Animais , Sulfatos de Condroitina/metabolismo , Portadores de Fármacos/metabolismo , Meia-Vida , Humanos , Receptores de Hialuronatos/metabolismo , Concentração Inibidora 50 , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Terapia de Alvo Molecular/métodos , Células NIH 3T3 , Nanopartículas/metabolismo , Células PC-3 , Tamanho da Partícula , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto , Zeína/metabolismoRESUMO
This study manufactured a horseshoe pattern (HP)-type electrical heating element based on a graphene/polylactic acid (GR/PLA) filament using CFDM (conveyor-fused deposition modeling) 3D printing technology, which is a new manufacturing process technology. CFDM 3D printing HP was fabricated in the different printing directions of 0°, 45°, and 90°. To confirm the effects of different 3D printing directions, the morphology, surface resistivity, and electrical heating properties of the different HPs were analyzed. In addition, the CFDM 3D-printed HPs made using different printing directions were printed on cotton fabric to confirm their applicability as fabric heating elements, and their electrical heating properties were measured. Regarding the morphology of the GR/PLA-HP, each sample was stacked according to the printing direction. It was also confirmed through FE-SEM images that the graphene was arranged according to the printing direction in which the nozzle moved. In the XRD pattern analysis, the GR/PLA-HP samples showed two diffraction peaks of PLA and graphene. The sizes of those peaks were increased in the order of 90° < 45° ≤ 0° according to the printing direction, which also affected the electrical and electric heating properties. The surface resistivities of the GR/PLA-HP samples were shown to be increased in the order of 0° < 45° < 90°, indicating that the electrical properties of GR/PLA HP printed at 0° were improved compared to those of the other samples. When 30 V was applied to three GR/PLA-HP samples according to the printing direction, the surface temperatures were decreased in the order of 0° < 45° < 90°, and the samples were indicated as 83.6, 80.6, and 52.5 °C, respectively; the same result was shown when the samples were printed on cotton fabric. Therefore, it was confirmed that the GR/PLA CFDM 3D-printed HP sample printed at 0° direction showed low surface resistivity and high surface temperature, so that improving the electrical heating properties.
RESUMO
The current outbreak of the beta-coronavirus (beta-Cov) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in December 2019. No specific antiviral treatments or vaccines are currently available. A recent study has reported that coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2 infection, is associated with neutrophil-specific plasma membrane rupture, and release excessive neutrophil extracellular traps (NETs) and extracellular DNAs (eDNAs). This mechanism involves the activation of NETosis, a neutrophil-specific programmed cell death, which is believed to play a crucial role in COVID-19 pathogenesis. Further progression of the disease can cause uncontrolled inflammation, leading to the initiation of cytokine storms, acute respiratory distress syndrome (ARDS), and sepsis. Herein, it is reported that DNase-I-coated melanin-like nanospheres (DNase-I pMNSs) mitigate sepsis-associated NETosis dysregulation, thereby preventing further progression of the disease. Recombinant DNase-I and poly(ethylene glycol) (PEG) are used as coatings to promote the lengthy circulation and dissolution of NET structure. The data indicate that the application of bioinspired DNase-I pMNSs reduce neutrophil counts and NETosis-related factors in the plasma of SARS-CoV-2 sepsis patients, alleviates systemic inflammation, and attenuates mortality in a septic mouse model. Altogether, the findings suggest that these nanoparticles have potential applications in the treatment of SARS-CoV-2-related illnesses and other beta-CoV-related diseases.