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Understanding the stability of mRNA loaded lipid nanoparticles (mRNA-LNPs) is imperative for their clinical development. Herein, we propose the use of size-exclusion chromatography coupled with dual-angle light scattering (SEC-MALS) as a new approach to assessing mRNA-LNP stability in pure human serum and plasma. By applying a dual-column configuration to attenuate interference from plasma components, SEC-MALS was able to elucidate the degradation kinetics and physical property changes of mRNA-LNPs, which have not been observed accurately by conventional dynamic light scattering techniques. Interestingly, both serum and plasma had significantly different impacts on the molecular weight and radius of gyration of mRNA-LNPs, suggesting the involvement of clotting factors in desorption of lipids from mRNA-LNPs. We also discovered that a trace impurity (~1 %) in ALC-0315, identified as its O-tert-butyloxycarbonyl-protected form, greatly diminished mRNA-LNP stability in serum. These results demonstrated the potential utility of SEC-MALS for optimization and quality control of LNP formulations.
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Cromatografia em Gel , Lipídeos , Nanopartículas , RNA Mensageiro , Humanos , RNA Mensageiro/genética , RNA Mensageiro/sangue , Nanopartículas/química , Lipídeos/química , Difusão Dinâmica da Luz , Plasma/química , Luz , Espalhamento de Radiação , Soro/química , Estabilidade de RNA , LipossomosRESUMO
Background: Hepatoblastoma is the most prevalent primary hepatic malignancy in children, comprising 80% of pediatric hepatic malignancies and 1% of all pediatric malignancies. However, traditional treatments have proven inadequate in effectively curing hepatoblastoma, leading to a poor prognosis. Methods: A literature search was conducted on multiple electronic databases (PubMed and Google Scholar). A total of 86 articles were eligible for inclusion in this review. Result: This review aims to consolidate recent developments in hepatoblastoma research, focusing on the latest advances in cancer-associated genomics, epigenetic studies, transcriptional programs and molecular subtypes. We also discuss the current treatment approaches and forthcoming strategies to address cancer-associated biological challenges. Conclusion: To provide a comprehensive summary of the molecular mechanisms associated with hepatoblastoma occurrence, this review highlights three key aspects: genomics, epigenetics, and transcriptomics. Our review aims to facilitate the exploration of novel molecular mechanisms and the development of innovative clinical treatment strategies for hepatoblastoma.
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Phosphorus (P) conveyed by surface runoff plays an essential role in regulating nutrient balance and primary production in estuarine waters. In this study, basic physiochemical properties, total phosphorus (TP, including speciation), particulate iron (PFe), particulate manganese (PMn), and particulate aluminum (PAl) of the surface water in the Pearl River Estuary (PRE) in different seasons were determined to investigate the spatiotemporal distribution characteristics of P and to identify the crucial factor controlling P migration and transformation in the freshwater-saltwater interaction zone. TP concentrations (28.88-233.68 µg·L-1) decreased with increasing salinity gradient owing to deposition and dilution. The proportions of P speciation followed a decreasing order as dissolved inorganic phosphorus (DIP, 37.3%) > particulate inorganic phosphorus (PIP, 22.7%) > dissolved organic phosphorus (DOP, 21.0%) > particulate organic phosphorus (POP, 19.0%). PIP was positively related to PFe, PMn, and PAl (P < 0.05), confirming their concurrent migration behaviors. In addition, the increase in salinity promoted the desorption of phosphate on the suspended particulate matters, which mainly took place near the freshwater-saltwater interface. A significant positive correlation (P < 0.001) between the solid-liquid phase partitioning coefficient (Kd) of phosphate and salinity indicated that PIP was present mainly in more stable forms in the brackish water. Most importantly, a better relationship between Kd and PMn (P < 0.01) supported our scientific hypothesis of the "load-unload" effect of Mn oxides on P:particulate-carrying phosphates transported from the freshwater zone tend to be desorbed and released into the brackish water.
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Intracellular Staphylococcus aureus (S. aureus), especially the methicillin resistant staphylococcus aureus (MRSA), are difficult to detect and eradicate due to the protection by the host cells. Antibacterial photodynamic therapy (aPDT) offers promise in treating intracellular bacteria, provided that selective damage to the bacteria ranther than host cells can be realized. According to the different nitroreductase (NTR) levels in mammalian cells and S. aureus, herein NTR-responsive photosensitizers (PSs) (T)CyI-NO2 were designed and synthesized. The emission and 1O2 generation of (T)CyI-NO2 are quenched by the 4-nitrobenzyl group, but can be specifically switched on by bacterial NTR. Therefore, selective imaging and photo-inactivation of intracellular S. aureus and MRSA were achieved. Our findings may pave the way for the development of more efficient and selective aPDT agents to combat intractable intracellular infections.
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Staphylococcus aureus Resistente à Meticilina , Fotoquimioterapia , Animais , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Staphylococcus aureus , Dióxido de Nitrogênio , Fotoquimioterapia/métodos , Antibacterianos/farmacologia , MamíferosRESUMO
Animal-derived basement-membrane matrices such as Geltrex are used to grow cells and tissues. Particularly, these are commonly applied to support tumor growth in animals for cancer research. However, a material derived from an animal source has an undefined composition, and may thus have unavoidable batch-to-batch variation in properties. To overcome these issues, a series of synthetic short peptides to form hydrogels is designed in combination with gelatin to promote cell adhesion and growth. The peptides have sequences of (X1Y1X2Y2)2 , where X1 and X2 are hydrophobic residues, while Y1 and Y2 are hydrophilic residues. The peptides spontaneously fold and self-assemble into a ß-sheet secondary structure upon contact with salts, and then aggregate to form hydrophilic networks of hydrogels. Hybrid hydrogels formed by mixing the peptide IEVEIRVK (IVK8) with gelatin are injectable and enzymatically degradable. The hybrid hydrogels at optimal compositions support SW480 and HepG2 tumor spheroid growth in vitro as effectively as Geltrex. More importantly, the peptide/gelatin hydrogels support tumor growth in a SW480 human colorectal adenocarcinoma xenograft mouse model. Altogether, the results illustrate that the synthetic peptide/gelatin hybrid hydrogel is a promising scaffold that can be used to support cell and tissue growth both in vitro and in vivo.
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Neoplasias Colorretais , Gelatina , Humanos , Animais , Camundongos , Membrana Basal , Modelos Animais de Doenças , Hidrogéis/farmacologia , Peptídeos/farmacologiaRESUMO
Objective To explore the mechanism of lipid metabolism disorder promoting the progress of lung cancer based on the oxidized low density lipoprotein(ox-LDL)/human lectin-like oxidized low density lipopro-tein receptor 1(LOX-1)signaling pathway.Methods Eighty-one identified lung adenocarcinoma tissues with paired adjacent non-cancerous tissues(at least 5 cm away from the tumor)were collected from our hospital,and the expression of LOX-1 was detected by immunohistochemistry.LOX-1 was overexpressed in lung adenocarcinoma cell lines(A549 and H1299 cells).Cell invasion ability was measured by Transwell.Cells were treated with different concentrations of oxLDL,and cellular LOX-1 expression was investigated.Results LOX-1 staining in the tumor was significantly stronger than that in the non-cancerous tissue samples(99.4 vs.16.2 for median H score,P<0.001).High LOX-1 expression was significantly correlated with low survival(P<0.001).As compared with the patients without lymph node metastasis,those with lymph node metastasis had higher LOX-1 level(83.2 vs.121.1 for median H score,P<0.01).Overexpression of LOX-1 in lung cancer cells significantly promoted the number of invasive and metastatic cells(P<0.01).In addition,LOX-1 was an essential functional target for oxLDL-induced metastasis of lung cancer cells.Itatinib inhibited the metastasis of LOX-1 overexpressed A549 in vitro.Conclusions With an increase in oxLDL level,the expression of LOX-1 increases.Up-regulation of LOX-1 promotes metastasis of lung cancer,and its mechanism may be related to activation of the JAK1/STAT6 signaling pathway.
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Objective:To investigate the conversion of stromal vascular fraction (SVF) in the microenvironment of radiation-induced skin injuries to provide guidance for clinical applications.Methods:Based on a random number table, C57BL/6N mice were categorized into four groups: the blank control, negative control, acute injury, and chronic injury groups, with each group containing 25 mice. The backs of mice in the blank control, acute injury, and chronic injury groups were exposed to 15 Gy X-ray irradiation. Then, the mice in the negative control, acute injury, and chronic injury groups were injected subcutaneously with the SVF derived from B6/G-R mice. The survival of these mice was observed 1, 3, 7, 14, and 21 d after the injection through fluorescence tracing and in vivo imaging. Accordingly, the clinical SVF injection regimens were optimized based on the experimental result of mice. Finally, local SVF injection was performed on different frequencies for patients in different wound conditions, with the efficacy being observed. Results:The fluorescence of SVF was observed from the tissue slices of the acute injury, chronic injury, and negative control groups 14 d post-injection. The result showed that the fluorescence intensity of SVF 1, 3, and 7 d post-injection was in the order of the negative control group > the acute injury group > the chronic injury group. The acute injury group ranked at the top and the chronic injury group remained at the bottom 14 d after the injection. The fluorescence of SVF in each group was barely detected 21 d after the injection. Compared to the negative control group, the acute injury group exhibited statistical differences only 14 d post-injection ( t = 4.11, P < 0.05), while the chronic injury group displayed statistical differences 1, 3, 7, and 14 d after the injection ( t = 3.88-5.74, P < 0.05). Furthermore, the acute injury group exhibited significantly higher fluorescence intensity of SVF than the chronic injury group ( t = 4.73-8.38, P < 0.05). The half-life of SVF for the negative control, acute injury, and chronic injury groups was 6.336, 6.014, and 2.163 d, respectively. As indicated by the application of SVF transplantation based on traditional surgical protocols in the clinical trial, SVF can significantly promote wound repair, with earlier SVF transplantation being more beneficial for wound healing. Conclusions:The conversion of SVF differs in the microenvironments of acute and chronic radiation-induced skin injuries. This can serve as an essential guide for the administration timing and injection frequency of SVF in clinical applications.
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The occurrence of early brain injury (EBI) significantly contributes to the unfavorable prognosis observed in patients with subarachnoid hemorrhage (SAH). During the process of EBI, a substantial quantity of iron permeates into the subarachnoid space and brain tissue, thereby raising concerns regarding its metabolism. To investigate the role and metabolic processes of excessive iron in neurons, we established both in vivo and in vitro models of SAH. We substantiated that ferritinophagy participates in iron metabolism disorders and promotes neuronal ferroptosis using an in vivo model, as detected by key proteins such as ferritin heavy chain 1, glutathione peroxidase 4, autophagy related 5, nuclear receptor coactivator 4 (NCOA4), LC3B, and electron microscopy results. By interfering with NCOA4 expression in vitro and in vivo, we confirmed the pivotal role of elevated NCOA4 levels in ferritinophagy during EBI. Additionally, our in vitro experiments demonstrated that the addition of oxyhemoglobin alone did not result in a significant upregulation of NCOA4 expression. However, simultaneous addition of oxyhemoglobin and hypoxia exposure provoked a marked increase in NCOA4 expression and heightened ferritinophagy in HT22 cells. Using YC-1 to inhibit hypoxia signaling in in vitro and in vitro models effectively attenuated neuronal ferroptosis. Collectively, we found that the hypoxic microenvironment during the process of EBI exaggerates iron metabolism abnormalities, leading to poor prognoses in SAH. The findings also offer a novel and potentially effective foundation for the treatment of SAH, with the aim of alleviating hypoxia.
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In this work, a silicon photodiode integrated with a piezoelectric membrane is studied by Kelvin probe force microscopy (KPFM) under modulated illumination. Time-dependent KPFM enables simultaneous quantification of the surface photovoltage generated by the photodiode as well as the resulting mechanical oscillation of the piezoelectric membrane with vertical atomic resolution in real-time. This technique offers the opportunity to measure concurrently the optoelectronic and mechanical response of the device at the nanoscale. Furthermore, time-dependent atomic force microscopy (AFM) was employed to spatially map voltage-induced oscillation of various sizes of piezoelectric membranes without the photodiode to investigate their position- and size-dependent displacement.
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Here, we present a case with genetically confirmed SCN. The main symptom of the child was recurring fever. The combination of antibiotics combined with G-CSF injection was proved to be insufficient, and the patient developed "solid" liver abscess. After undergoing surgical anatomical hepatic lobectomy, the child's infection symptoms showed improvement. The postoperative culture of the purulent material from the liver infection lesion revealed an infection with Staphylococcus aureus. Our case raises the possibility of pathogen sources and routes of infection, clinical characteristics, and effective treatment for SCN patients with concomitant liver abscess.
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Short- and medium-chain chlorinated paraffins (SCCPs and MCCPs) have attracted significant attention because of their persistence, biotoxicity, bioaccumulation, and long-range migration. Given their worldwide detection in a variety of environmental matrices, concerns related to the high exposure risks of SCCPs and MCCPs to humans have grown. Thus, knowledge of the contamination patterns of SCCPs and MCCPs and their distribution characteristics in the vivo exposure of humans is of great importance. However, little information is available on the contamination of SCCPs and MCCPs in human blood/plasma/serum, mainly because of the difficulty of sample preparation and quantitative analysis. In this study, a new blood sample pretreatment method based on Percoll discontinuous density gradient centrifugation was developed to separate plasma, red blood cells, white blood cells, and platelets from human whole blood. A series of Percoll sodium chloride buffer solutions with mass concentrations of 1.095, 1.077, and 1.060 g/mL were placed in a centrifuge tube from top to bottom to establish discontinuous density gradients. The dosage for each density gradient was 1.5 mL. Human whole blood samples mixed with 0.85% sodium chloride aqueous solution were then added to the top layer of the Percoll sodium chloride solution. After centrifugation, the whole blood was separated into four components. The plasma was located at the top layer of the centrifuge tube, whereas the platelets, white blood cells, and red blood cells were retained at the junction of the various Percoll sodium chloride solutions. The sampling volume of human whole blood and incubation time were optimized, and results indicated that an excessively long incubation time could lead to hemolysis, resulting in a decrease in the recoveries of SCCPs and MCCPs. Therefore, a sampling volume of 1.5 mL and incubation time of 10 min at 4 â were adopted. The cells of the blood components were further broken and extracted by ultrasonic pretreatment, followed by multilayer silica gel column chromatography for lipid removal. The use of 80 mL of n-hexane-dichloromethane (1â¶1, v/v) and 50 mL of dichloromethane as the elution solvents (collected together) for the gel column separated the SCCPs and MCCPs from the lipid molecules in the blood samples. Gas chromatography-electron capture negative ion-low resolution mass spectrometry (GC-ECNI-LRMS) was used to determine the SCCPs and MCCPs. Quantification using the corrected total response factor with degrees of chlorination was achieved with linear corrections (R2=0.912 and 0.929 for the SCCPs and MCCPs, respectively). The method detection limits (MDLs) for the SCCPs and MCCPs were 1.57 and 8.29 ng/g wet weight (ww, n=7), respectively. The extraction internal standard recoveries were 67.0%-126.6% for the SCCPs and 69.5%-120.5% for the MCCPs. The developed method was applied to determine SCCPs and MCCPs in actual human whole blood samples. The contents of SCCPs and MCCPs were 10.81-65.23 and 31.82-105.65 ng/g (ww), respectively. Red blood cells exhibited the highest contents of CPs, followed by plasma, white blood cells, and platelets. The proportions of SCCPs and MCCPs in red blood cells and plasma were 70% and 66%, respectively. In all four components, the MCCP contents were higher than the SCCP contents, and the ratios of MCCPs to SCCPs ranged from 1.04 to 3.78. Similar congener patterns of SCCPs and MCCPs were found in the four components of human whole blood. C10-CPs and C14-CPs were predominantly observed in the SCCPs and MCCPs, respectively. In summary, a simple and efficient method was proposed to determine low concentrations of SCCPs and MCCPs in human blood with high sensitivity and selectivity. This method can meet requirements for the quantitative analysis of SCCPs and MCCPs in human blood components, thereby providing technical support for human health risk assessment.
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Hidrocarbonetos Clorados , Parafina , Humanos , Parafina/análise , Cloreto de Metileno/análise , Hidrocarbonetos Clorados/análise , Elétrons , Cloreto de Sódio/análise , Monitoramento Ambiental/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Lipídeos , ChinaRESUMO
Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is a chronic autoimmune disorder characterized by inflammation. However, currently available disease-modifying anti-IBD drugs exhibit limited efficacy in IBD therapy. Furthermore, existing therapeutic approaches provide only partial relief from IBD symptoms and are associated with certain side effects. In recent years, a novel category of nanoscale membrane vesicles, known as plant-derived exosome-like nanoparticles (PDENs), has been identified in edible plants. These PDENs are abundant in bioactive lipids, proteins, microRNAs, and other pharmacologically active compounds. Notably, PDENs possess immunomodulatory, antitumor, regenerative, and anti-inflammatory properties, making them particularly promising for the treatment of intestinal diseases. Moreover, PDENs can be engineered as targeted delivery systems for the efficient transport of chemical or nucleic acid drugs to the site of intestinal inflammation. In the present study, we provided an overview of PDENs, including their biogenesis, extraction, purification, and construction strategies, and elucidated their physiological functions and therapeutic effects on IBD. Additionally, we summarized the applications and potential of PDENs in IBD treatment while highlighting the future directions and challenges in the field of emerging nanotherapeutics for IBD therapy.
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Background: Osteoarticular tuberculosis (TB) is an uncommon form of extrapulmonary TB. In this study, we analyzed the epidemiological characteristics, common sites, and drug resistance profiles of osteoarticular TB infections occurring in southwest China. Methods: A total of 3,254 cases of patients clinically diagnosed with osteoarticular TB infections between 2013 and 2021 were retrospectively analyzed. Patients' demographic and clinical characteristics were collected. Drug sensitivity testing was performed using the microporous plate ratio method. Chi-squared analysis was used to analyze the rates of and trends in mycobacterial isolates. Results: Of the 3,254 patients, 1,968 (60.5%) were men and boys, and 1,286 (39.5%) were women and girls; patients' ages ranged from 1 to 91 years, with an average of 42 ± 19.3 years. In terms of disease, 2,261 (69.5%) had spinal TB, mainly thoracic (815, 36%) or lumbar (1,080, 48%); joint TB was found in 874 cases (26.9%), mainly occurring in the knee (263, 30%) or hip (227, 26%); and both spinal and joint TB were observed in 119 cases (3.7%). Drug susceptibility tests were performed on 241 isolated strains of MTB; 70 strains (29.0%) were resistant to at least one drug, and MDR-TB and XDR-TB were observed in 7.1 and 1.2% of strains, respectively. Conclusions: In southwest China over this period, osteoarticular TB mainly affected middle-aged and young men with poor nutritional status. Patients from ethnic minority areas also accounted for a large proportion of cases. Spinal TB is prone to occur in the lumbar and thoracic vertebrae, and joint TB is prone to occur in the lower limb joints. Additionally, there has been an increasing trend in the number of TB cases over the past 9 years, and drug resistance has also increased.
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Drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), pose a serious threat to human life. Therefore, there is urgent need to develop antibiotics with new chemical structures and antibacterial mechanisms, especially those that elicit little drug resistance after long-term use. Herein we synthesized three novel ruthenium complexes (Ru1-Ru3) containing the enaminone structures for the first time. At a concentration of 5â µM, Ru1-Ru3 can lead to a CFU reduction of about 5 log units towards S. aureus and MRSA. Interestingly, Ru3 displayed rapid bactericidal effects and could decrease the CFU numbers of both pathogens by 5 log units within 40â min. The control compounds (Ru4 and Ru5) without the enaminone structures displayed very poor antibacterial activity under the same conditions. Moreover, S. aureus did not show apparent drug resistance towards Ru3 after 20 passages incubation with a sublethal concentration. These results highlight the critical role of enaminone structures for antibacterial applications.
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Staphylococcus aureus Resistente à Meticilina , Humanos , Staphylococcus aureus , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/química , Esterilização , Resistência a MedicamentosRESUMO
Background: Hepatoblastoma (HB) is the most common liver malignancy in childhood with poor prognosis and lack of effective therapeutic targets. Single-cell transcriptome sequencing technology has been widely used in the study of malignant tumors, which can understand the tumor microenvironment and tumor heterogeneity. Materials and methods: Two children with HB and a healthy child were selected as the research subjects. Peripheral blood and tumor tissue were collected for single-cell transcriptome sequencing, and the sequencing data were compared and analyzed to describe the differences in the immune microenvironment between children with HB and normal children. Results: There were significant differences in the number and gene expression levels of natural killer cells (NK cells) between children with HB and normal children. More natural killer cells were seen in children with HB compared to normal control. KIR2DL were highly expressed in children with HB. Conclusion: Single-cell transcriptome sequencing of peripheral blood mononuclear cells (PBMC) and tumor tissue from children with HB revealed that KIR2DL was significantly up-regulated in NK cells from children with HB. HLA-C molecules on the surface of tumor cells interact with inhibitory receptor KIR2DL on the surface of NK cells, inhibiting the cytotoxicity of NK cells, resulting in immune escape of tumors. Inhibitors of related immune checkpoints to block the interaction between HLA-C and KIR2DL and enhance the cytotoxicity of NK cells, which may be a new strategy for HB treatment.
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Objective: To evaluate the feasibility of reducing the injection velocity and volume of contrast agent according to BMI, and the effect of body weight (BW), body surface areaï¼BSAï¼, body mass indexï¼BMIï¼ï¼and blood volume (BV) on aortic contrast enhancement when the voltage of third-generation dual-source CT is selected at 70 KV. Methods: A total of 280 patients selected at 70 KV were randomly divided into an experimental group and a control group. Each group was divided into 7 subgroups according to BMI ≤20, 20-21, 21-22, 22-23, 23-24, 24-25, and 25-26. The experimental group uses 2.3/2.4/2.5/2.6/2.7/2.8/2.9 ml/s injection speed with 350 mgI/ml contrast agents according to the subgroups; injection time was fixed at 10 s. In the control group, the fixed injection flow rate was 3.5 ml/s, time was 12 s with a total of 42 ml. Subjects in both groups were inspected to adaptive prospective ECG-gating sequence scanning, and subjective and objective image quality of the two groups were compared using Student's t-test. BMI, BSA, and BV were calculated from the patient's body weight and height. We assess the relationship between aortic attenuation and BW, BMI, BV, and BSA using regression analysis or correlation analysis. Results: Significant differences exist in vascular enhancement between the two groups; SNR and CNR of objective image quality in the experimental group were lower than those in the control group (P < 0.05). Both groups had the same subjective image scores (P > 0.05). The number of vessels in the optimal enhancement range counts more in the experimental group than in the control group (χ2 value = 334.25, P ï¼ 0.05). In the control group, a weak to medium correlation was seen between vascular enhancement and BMI (r = -0.20), BW (r = -0.42), BSA (r = -0.46), and BV (r = -0.48) (P ï¼ 0.05 for all). Conclusions: Compared to BW, BSA, and BV, a weaker negative correlation exists between vascular enhancement and BMI when ATVS selects 70 KV. However, as a much easier way to operate, the stepped low flow and low-contrast agent injection based on BMI was feasible, and the image quality was more homogenized than that of the control group.
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Iodo , Índice de Massa Corporal , Peso Corporal , Meios de Contraste , Humanos , Estudos Prospectivos , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador/métodosRESUMO
As a group of chronic and idiopathic gastrointestinal (GI) disorders, inflammatory bowel disease (IBD) is characterized by recurrent intestinal mucosal inflammation. Oral administration is critical for the treatment of IBD. Unfortunately, it is difficult to target the bowel located in the GI tract due to multiple physical barriers. The unique physicochemical properties of nanoparticle-based drug delivery systems (DDSs) and their enhanced permeability and retention effects in the inflamed bowel, render nanomedicines to be used to implement precise drug delivery at diseased sites in IBD therapy. In this review, we described the pathophysiological features of IBD, and designed strategies to exploit these features for intestinal targeting. In addition, we introduced the types of currently developed nano-targeted carriers, including synthetic nanoparticle-based and emerging naturally derived nanoparticles (e.g., extracellular vesicles and plant-derived nanoparticles). Moreover, recent developments in targeted oral nanoparticles for IBD therapy were also highlighted. Finally, we presented challenges associated with nanotechnology and potential directions for future IBD treatment.
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Doenças Inflamatórias Intestinais , Nanopartículas , Administração Oral , Sistemas de Liberação de Medicamentos , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , NanomedicinaRESUMO
Tissue engineering involves the transplantation of stem cell-laden hydrogels as synthetic constructs to replace damaged tissues. However, their time-consuming fabrication procedures are hurdles to widespread application in clinics. Fortunately, similar to cell banking, synthetic tissues could be cryopreserved for subsequent central distribution. Here, we report the use of trehalose and gellan gum as biomacromolecules to form a cryopreservable yet directly implantable hydrogel system for adipose-derived stem cell (ADSC) delivery. Through a modified cell encapsulation method and a preincubation step, adequate cryoprotection was afforded at 0.75 M trehalose to the encapsulated ADSCs. At this concentration, trehalose demonstrated lower propensity to induce apoptosis than 10% DMSO, the current gold standard cryoprotectant. Moreover, when cultured along with trehalose after thawing, the encapsulated ADSCs retained their stem cell-like phenotype and osteogenic differentiation capacity. Taken together, this study demonstrates the feasibility of an "off-the-shelf" biomacromolecule-based synthetic tissue to be applied in widespread tissue engineering applications.
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Hidrogéis , Osteogênese , Colágeno , Criopreservação , Hidrogéis/farmacologia , Polissacarídeos Bacterianos , Células-Tronco , Açúcares , Trealose/farmacologiaRESUMO
As a common pulmonary malignant disease, lung adenocarcinoma exhibits high mortality and morbidity rate. Phospholipase Cδ1 (PLCD1), an enzyme involved in the homeostasis of energy metabolism, is downregulated in lung adenocarcinoma. According to GEPIA, origin recognition complex 1 (ORC1) is a highly expressed gene in lung adenocarcinoma and is negatively associated with PLCD1. To the best of our knowledge, the present study was the first to investigate the role of ORC1 in regulating PLCD1 in lung adenocarcinoma. According to TCGA database, low expression of PLCD1 was correlated with the low overall survival rate of patients suffering from lung adenocarcinoma. The protein and mRNA expression levels of PLCD1 and ORC1 were detected in A549 cells by western blot analysis and reverse transcription-quantitative PCR, respectively. Cell proliferation, invasion and migration were analyzed by MTT, colony formation, Transwell and wound healing assay. Immunofluorescence staining was adopted to estimate the content of Ki67 and western blot was applied for the evaluation of PLCD1, MMP2, MMP9, E-cadherin, N-cadherin, vimentin, Snail and ORC. The binding interaction between ORC1 and PLCD1 was analyzed using chromatin immunoprecipitation and luciferase reporter enzyme gene assays. The results indicated that PLCD1 was lowly expressed in lung adenocarcinoma cells in comparison with that in 16HBE. When PLCD1 was overexpressed in cancer cells, cell proliferation, invasion and migration were significantly inhibited. However, in the presence of both ORC1 and PLCD1 overexpression, the suppressive effects of PLCD1 overexpression alone on cell proliferation, invasion, migration and EMT were attenuated. In conclusion, ORC1 was indicated to inhibit PLCD1, thus regulating the proliferation, migration and EMT processes of lung adenocarcinoma cells, which suggested that ORC1 might be a target for the treatment of lung adenocarcinoma.
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Chemodynamic therapy (CDT) is novel and promising for cancer treatment, however, the potential systematic toxicity of the used nanoparticles is still a big concern. In this work the biocompatible hypocrellin A-Fe(III) nanoparticles (HA-Fe(III) NPs) were synthesized and studied. The CDT effect of HA-Fe(III) NPs in the dark is negligible but can be photo-activated upon red light irradiation, which is meaningful to realize precise CDT treatment by selective light irradiation. Moreover, HA-Fe(III) NPs can also generate O2Ë-, which may be converted into H2O2 to further enhance the CDT effect. As a result, HA-Fe(III) NPs had little cytotoxicity in the dark at the concentration up to 200 µg ml-1, but exhibited efficient CDT activity upon red light irradiation under both normoxic and hypoxic conditions. The in vivo results also showed that HA-Fe(III) NPs can efficiently inhibit tumor growth upon 628 nm light irradiation.