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1.
J Hazard Mater ; 421: 126740, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34333409

RESUMO

Azo dye pollution has become a worldwide issue, and the current treatment methods can hardly meet the expected emission standards. Microbial electrochemical systems (MESs) show promising applications for decolorization, but their performance critically depends on the microorganisms. Electrode modification is an interesting method of improving decolorization performance. However, the mechanisms of how the modification can affect microbial communities and the decolorization process remain unclear. Here, a modified anode with polyaniline (PANI) and graphene was fabricated via electro-deposition. Consequently, the highest decolorization efficiency was obtained. The Congo red (CR) decolorization rate of the MESs with the PANI/graphene-modified electrode (PG) reached 90% at 54 h. By contrast, the CR decolorization rates of the MESs with the PANI-modified electrode (P) and those of the MESs with the unmodified electrode (C) only reached 68% and 79%, respectively. Results of the microbial community analysis showed abundant Methanobrevibacter arboriphilus in PG (11%), which was 5.5 times that in C (2%) at 18 h. This phenomenon may be related to the rapid decolorization. The upregulated metabolism pathways, including arginine and proline metabolism, purine metabolism, arginine biosynthesis, and riboflavin metabolism, provided more electron shuttles and redox mediators that facilitated the extracellular electron transfer. Therefore, the PG-modified electrode facilitated the decolorization by altering certain metabolic pathways. This study can help to improve the guideline on the potential application of MESs for wastewater treatment.


Assuntos
Compostos Azo , Grafite , Compostos de Anilina , Corantes , Eletrodos , Águas Residuárias
3.
Biomacromolecules ; 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34723499

RESUMO

Hyaluronic acid (HA) based hydrogels are one of most functional natural biomaterials in the field of cartilage tissue engineering (CTE). Even with the promising advantages of HA hydrogels, the complicated mechanical properties of the native cartilage have not been realized, and fabricating HA hydrogels with excellent mechanical properties to make them practical in CTE still remains a current challenge. Here, a strategy that integrates hydrogels and nanomaterials is shown to form a HA hydrogel with sufficient mechanical loading for cartilage tissue production and recombination. Cellulose nanofibrils (CNFs) are promising nanomaterial candidates as they possess high mechanical strength and excellent biocompatibility. In this study, we developed methacrylate-functionalized CNFs that are able to photo-crosslink with methacrylated HA to fabricate HA/CNF nanocomposite hydrogels. The present composite hydrogels with a compressive modulus of 0.46 ± 0.05 MPa showed adequate compressive strength (0.198 ± 0.009 MPa) and restorability, which can be expected to employ as a stress-bearing tissue such as articular cartilage. Besides, this nanocomposite hydrogel could provide a good microenvironment for bone marrow mesenchymal stem cell proliferation, as well as chondrogenic differentiation, and exhibit prominent repair effect in the full-thickness cartilage defect model of SD rats. These results suggest that the HA/CNF nanocomposite hydrogel creates a new possibility for fabricating a scaffold in CTE.

4.
Cell Biol Toxicol ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34755307

RESUMO

The modern categories of endogenous non-coding RNAs, namely circular RNAs (circRNAs), involved within the carcinogenesis and progression of various human cancers. The fundamental aim of the current investigation was the evaluation of the hsa_circ_0014130 expressions, their biological functions, and potential regulatory network in bladder cancer. The level of expression for hsa_circ_0014130 was evaluated by qRT-PCR, and its relationships to clinicopathological features and survival outcomes of cases experiencing cancer of the bladder were scrutinized. The impact of hsa_circ_0014130 expressions on biological attitudes of bladder cancer cells in vitro was investigated. The interactions between hsa_circ_0014130 and microRNA (miRNA) sponge, miRNA, and its direct targets were determined by RNA pull-down as well as luciferase reporter gene assay. The correlations of their expression were determined by Pearson's correlation analysis. Rescue experiments were carried out to identify the biological roles of the regulation network. The expressions of hsa_circ_0014130 were markedly ameliorated in bladder cancer samples and linked with aggressive characteristics and unfavorable survival. Ectopic expression of hsa_circ_0014130 clearly enhanced the differentiation, proliferative, migratory, invasive potential of the cell in bladder cancer, and the development of tumor xenograft in vivo, while malignant biological behaviors were inhibited by hsa_circ_0014130 knockdown. The expression of hsa_circ_0014130 was tied to miR-132-3p in a negative manner with the cells and tissues of bladder cancer. hsa_circ_0014130 function as a competitive endogenous RNA for miR-132-3p to play oncogenic roles in bladder cancer cells. On the other hand, KCNJ12 was a straightforward target of miR-132-3p at the downstream, and the expressions of KCNJ12 were inversely related to that of miR-132-3p. Furthermore, a significantly positive correlation was found between hsa_circ_0014130 and KCNJ12 mRNA expression. More importantly, the oncogenic impact of hsa_circ_0014130 on bladder cancer cells was partly suppressed by ectopic expression of miR-132-3p or KCNJ12 knockdown. The underlined data revealed that hsa_circ_0014130 exerted its biological roles by regulating miR-132-3p/KCNJ12 expression. Further research revealed hsa_circ_0014130/miR-132-3p/KCNJ12 axis has participated in the Epithelial-mesenchymal transition (EMT) progress and GSK3ß/AKT signaling pathway. hsa_circ_0014130 works as a sponge of miR-132-3p to advance the oncogenesis and metastasis of bladder cancer by regulation of the KCNJ12 expression. These achievements might ameliorate the comprehension of tumor pathogenesis and provide novel therapeutic targets for cancer of the bladder.

5.
J Invasive Cardiol ; 33(11): E877-E883, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34653957

RESUMO

BACKGROUND AND AIM: Patients with chronic dialysis dependency undergoing percutaneous coronary intervention (PCI) are at a greater risk of hemorrhagic and ischemic events. Due to their exclusion from randomized clinical trials, the optimal antithrombotic regimen for this population remains unknown. Bivalirudin has been associated with fewer hemorrhagic complications than unfractionated heparin (UFH) in patients undergoing PCI. We evaluated major adverse cardiac event (MACE) and hemorrhagic event rates for an antithrombotic regimen using bivalirudin or UFH during PCI in acute coronary syndrome (ACS) patients with chronic dialysis dependency. METHODS: A retrospective study was performed, including 211 patients on dialysis undergoing PCI due to ACS from January 2014 to April 2019 at the China-Japan Friendship Hospital. Patients were divided into 2 groups based on anticoagulation regimen: the bivalirudin group (86 cases) or the UFH group (125 cases) during and after PCI. Statistical analyses were used to compare MACE and hemorrhagic events between groups at 30 days after PCI. RESULTS: No patients experienced stent thrombosis within 30 days after PCI regardless of anticoagulant. There was no difference in the incidence of MACE in the bivalirudin group compared with the UFH group (6.98% vs 8.80%, respectively; P>.05). The rate of hemorrhagic events in the bivalirudin group was significantly lower than in the UHP group (5.81% vs 18.4%, respectively; P<.05), particularly for rates of mild bleeding (4.65% vs 15.2%, respectively; P<.05). There were no significant differences in rates of severe bleeding between the bivalirudin and UFH groups (1.16% vs 4.00%, respectively; P>.05), although fewer severe hemorrhagic events occurred in the bivalirudin group. CONCLUSION: Bivalirudin was associated with fewer bleeding events following PCI in individuals with end-stage renal disease on dialysis.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/cirurgia , Anticoagulantes/efeitos adversos , Antitrombinas/efeitos adversos , Heparina/efeitos adversos , Hirudinas/efeitos adversos , Humanos , Fragmentos de Peptídeos/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Proteínas Recombinantes , Diálise Renal/efeitos adversos , Estudos Retrospectivos
6.
Ann Palliat Med ; 10(9): 9993-10004, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34628923

RESUMO

BACKGROUND: The prognosis of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) between patients with diabetes mellitus (DM) and those without DM is unknown. This study aimed to investigate whether DM has adverse effects on CTO PCI patients. METHODS: This single-center retrospective study included consecutive patients who underwent PCI for CTO at the China-Japan Friendship Hospital (Beijing, China) between January 2016 and April 2019. The clinical outcomes during follow-up were compared between patients with DM and those without DM. RESULTS: The analysis included 187 patients (152 males) aged 62.6±11.5 years. A total of 99 participants (52.9%) had DM, which involved a higher body mass index (BMI) and triglyceride level than those without DM (P<0.05). Participants with DM and those without DM had similar PCI success rates (89.9% vs. 95.4%, respectively) and complete revascularization rates (82.8% vs. 84.1%, respectively). There were no significant differences between groups in the rates of all-cause mortality, cardiac death, major adverse cardiovascular events (MACEs), readmission, recurrence of angina, target vessel revascularization (TVR), or myocardial infarction (MI) during a median follow-up of 20.5 months. Multivariable logistic regression revealed that CTO in a coronary branch vessel was associated with higher odds of all-cause death (odds ratio (OR): 53.56; 95% confidence interval (CI): 2.48 to 1,155.41; P<0.05) and failure of PCI for CTO (OR: 5.40; 95% CI: 1.263 to 23.098; P<0.05). Additionally, PCI for single CTO was associated with lower odds of MACEs (OR: 0.300; 95% CI: 0.118 to 0.765; P<0.05). CONCLUSIONS: The performance of PCI for CTO has a high success rate in both patients with DM and those without DM, and clinical outcomes are comparable between groups.


Assuntos
Oclusão Coronária , Diabetes Mellitus , Intervenção Coronária Percutânea , Doença Crônica , Angiografia Coronária , Oclusão Coronária/cirurgia , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
7.
Aging (Albany NY) ; 13(19): 22843-22855, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34607973

RESUMO

OBJECTIVES: Allicin is an allyl 2-propenethiosulfinate or diallyl thiosulfinate acid with cardioprotective effects in myocardial ischemia/reperfusion (MI/R) injury. This study aims to examine the underlying mechanism by which Allicin protects against MI/R. METHODS: C57BL6 mice were subjected to either sham or MI/R surgery, and mice in the Allicin group were injected with Allicin (5 mg/ml) before the induction of ischemia. The cardiac function and histopathology of experimental mice were evaluated by ultrasound quantification and Masson staining. We next measured the capillary angiogenesis of the peri-infarct area by Masson staining and immunohistochemical staining. The miRNA microarray was carried out to examine the expressed miRNAs in MI/R tissues and corresponding normal tissues. Real-time quantitative polymerase chain reaction (q-PCR) was performed to validate the selected miRNA-19α-3p gene expression. Besides, we evaluated the myocardial lactate dehydrogenase and COX-2 by immunofluorescence staining. The western blot analysis was used to evaluate the protein levels of p-AKT, p-PI3K, p-mTOR, COX-2, and VEGF protein in the Allicin and Model group. In vitro study, LPS stimulated Tie2 expressing macrophages were cultured in an ischemic buffer. We evaluated the accumulation of VEGF by fura-2/AM fluorescence. Besides, Western blotting was performed to examine the protein levels of p-PI3K, p-AKT, p-mTOR, VEGF, COX2, and MMP2. The PI3K inhibitor was applied to investigate whether Allicin-induced myocardial ischemia-reperfusion injury protection is mediated via the PI3K/AKT pathway. And the miR-19α-3p mimic/inhibitor were transfected to promote/inhibit the expression of miR-19a-3p for verifying the regulation of miR-19a-3p on PI3K pathway. RESULTS: Allicin pretreatment significantly improved I/R-induced cardiac function damage. Furthermore, Allicin could repress cardiac fibrosis, as evidenced by reduced areas of cardiac fibrosis. Allicin's effect on the MI/R was associated with increased capillary angiogenesis. Microarray analysis exposed that miR-19a-3p down-regulated PIK3CA (PI3K) expression by directly targeting the PIK3CA gene. The regulation of the angiogenesis pathway and gene miRNA-19a-3p might affect the Allicin-induced MI/R protection. Immunofluorescence staining revealed that COX-2 and myocardial lactate dehydrogenase were significantly increased after Allicin treatment. Furthermore, western blot analysis demonstrated that p-AKT, p-PI3K, p-mTOR, COX-2, and VEGF protein levels were also increased in the Allicin group. In vitro study, the protein levels of p-PI3K, p-AKT, p-mTOR, VEGF, COX2, and MMP2 were significantly increased in the Allicin-treated Tie2 expressing macrophages. These effects were partially reversed by PI3K inhibitor (Wortmannin) treatment. MiR-19α-3p plays an important role in myocardial I/R injury. It could regulate the activity of the PI3K-AKT pathway. And inhibition of miR-19a-3p promoted angiogenesis by regulating PI3K/AKT pathway. CONCLUSIONS: Allicin pretreatment protects against myocardial I/R and activating the miR-19a-3p/PI3K/AKT pathway.

8.
Histol Histopathol ; : 18381, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34668176

RESUMO

Cardiomyocyte apoptosis is a fundamental pathogenic factor leading to myocardial ischemia/reperfusion (MI/R) injury. The long non-coding RNA (IncRNA) TUG1 regulates apoptosis in various cell types. We report here that TUG1 expression is induced in mouse heart following MI/R injury as well as in cardiomyocytes subjected to simulated ischemia/reperfusion (SI/R) in vitro. Clinically, TUG1 expression is also elevated in plasma from patients with acute myocardial infarction (AMI), which implies its potential application as a disease biomarker. Functionally, TUG1 overexpression promotes, and its knockdown reduces SI/R-induced lactate dehydrogenase (LDH) release and caspase-3 activity in cardiomyocytes in vitro, illustrating that TUG1 exacerbates SI/R-induced apoptosis. Furthermore, in vivo, TUG1 aggravates MI/R injury in a mouse model, and subsequent observations show concurrent increased apoptosis of cardiomyocytes. Hence, this study unveils a clinical relevance and functional role of TUG1 in MI/R injury, and also implicates that targeting TUG1 may have therapeutic effects in treating MI/R injury.

9.
J Clin Lab Anal ; 35(11): e23989, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34558723

RESUMO

Recent studies have shown that miR-802 is abnormally expressed in many tumors. miR-802 is expressed at low levels in tissues and cells of gastric cancer, colorectal cancer, breast cancer, cervical cancer, epithelial ovarian cancer, tongue squamous cell carcinoma, oral squamous cell carcinoma, esophageal squamous cell carcinoma, laryngeal squamous cell carcinoma, and melanoma. In contrast, miR-802 is overexpressed in hepatocellular carcinoma, bladder urothelial cancer, osteosarcoma, and cholesteatoma tissue cells. It should be noted that the results of studies on the expression of miR-802 in pancreatic cancer, prostate cancer, and lung cancer are inconsistent. Current studies have found that miR-802 can target and regulate genes in different tumors, and affect the regulation of the Wnt signaling pathway, EMT signaling pathway, PI3K/AKT signaling pathway, ERK signaling pathway, and Hedgehog signaling pathway. At the same time, miR-802 is regulated by the endogenous competition of four ceRNAs, including circDONSON, IGFL2-AS1, MIR155HG, and MIR4435-2HG. This article reviews the abnormal expression of miR-802 in a variety of tumors, expounds the mechanism by which miR-802 affects tumor progression by regulating different target genes, and elaborates the network of miR-802-related ceRNAs. We also summarized the limitations of miR-802 research and looked forward to the potential application of miR-802 in the diagnosis and prognosis of tumors.

10.
Nanoscale ; 13(38): 16084-16093, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34549749

RESUMO

Bio-mass materials have been selected as one of the advanced electromagnetic (EM) functional materials due to their natural porous framework for dynamically and flexibly optimizing the EM response property. Herein, we demonstrate sulfur-doped wood-derived porous carbon EM materials (SPC) for optimizing the EM response performance via the coupling between doped heterostructures and the original 3D microchannels. The experimental results reveal that both the dielectric loss capacity and interfacial impedance matching could be increased by the sulfur-doped heterostructures. By tailoring the sulfur content, the microwave absorption (normalized RLmin) of SPC could be optimized to -15.90 dB mm-1, while the effective absorption bandwidth (EABRL≤-10 dB) could cover the K band. Moreover, the shielding effectiveness of SPC can be enhanced from 10 dB to 30 dB with the assistance of water, ascribed to the super-wettability performance. This present study provides a novel strategy to further optimize the EM response performance of wood-derived materials, and meanwhile could be widely extended to other bio-mass absorbers.

11.
Aging (Albany NY) ; 13(15): 19643-19656, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34343971

RESUMO

PURPOSE: To investigate the protective effect and mechanism of allicin on myocardial ischemia-reperfusion (MI/R) injury. METHODS: We investigated the mechanisms by which allicin attenuated the MI/R injury by focusing on phosphoinositide 3-kinase, G protein coupled receptor kinases 2, phospholipase Cγ and cardiomyocyte apoptosis. Sixty male mice were randomly assigned into three groups: repeated MI/R (model), sham-operated (control), and MI/R+ allicin group (allicin). Ultrasound examination was used to examine the cardiac function. Masson staining was used to evaluate the myocardial infarct area. TUNEL assay was performed to examine the anti-apoptotic effect of allicin. Differentially expressed genes (DEGs) and pathways were analyzed by mRNA microarray analysis. Immunofluorescence staining and western blot were carried out to detect the effect of allicin on the PI3K. A pan-PLC activator, m-3M3FBS, was applied to investigate whether allicin induced cardiomyocyte apoptosis was via the GRK2/PLC/IP3R signaling pathway. RESULTS: Masson staining and the TUNEL assay revealed that allicin reduced infarct size and played an anti-apoptotic role in M/IR. Ultrasound examination revealed that allicin improved cardiac function after M/IR injury. Gene ontology analysis indicated that the calcium signaling pathway and PI3KCA(PI3K) were selected. Immunofluorescence staining and western blot exposed that PI3K was activated by allicin during MI/R injury. Fura-2AM staining revealed that the PI3K -mediated GRK2/PLC-γ/IP3R pathway may be involved in the protective effect of allicin on MI/R injury. CONCLUSIONS: Allicin has a protective effect on MI/R injury. This effect might be associated with the inhibition of Ca2+ overload-induced apoptosis and the inhibition of the PI3K -mediated GRK2/PLC-γ/IP3R signaling pathway.

12.
Pak J Pharm Sci ; 34(1): 129-134, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34248012

RESUMO

The aim of this study was to examine the effects of glycosaminoglycan (GAG) from Urechis unicinctus on the P2Y1 receptor pathway and expression of related factors in rat platelets. The concentration of calcium ion (Ca2+) in rat platelets was determined by double wavelength Fura-2 fluorescence spectrophotometry, and the concentrations of inositol trisphosphate (IP3) and glycoprotein IIb/IIIa (GPIIb/IIIa) in rat platelets were measured using the enzymatic immunoassay method. The phosphorylation levels of phospholipase C (PLC), phospholipase A2 (PLA2), protein kinase C (PKC), and p38 mitogen-activated protein kinase (p38MAPK) were also detected by Western blot. It was found that the GAG from U. unicinctus significantly reduced the Ca2+ and IP3 levels in rat platelets (p<0.05, p<0.01). Moreover, medium and high concentrations of GAG significantly reduced the concentration of the platelet membrane GPIIb/IIIa in rats (p<0.05, p<0.01). The phosphorylation levels of PLC, PLA)2), PKC and p38MAPK in rat platelets were also inhibited by GAG and P)2)Y)1) receptor blocker MRS2179 (p<0.05, p<0.01). However, the degree of inhibition of GAG was lower than that of MRS2179. The results laid a foundation for further utilization of the glycosaminoglycan.

13.
J Control Release ; 336: 621-634, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34246701

RESUMO

Immune checkpoint antibodies have emerged as novel therapeutics, while many patients are refractory. Researchers had identified tumor-associated macrophages (TAMs) is the pivotal factor involved in immune resistance and that manipulation of TAMs functions would improve the immunotherapies effectively. NF-κB pathway was one of the master regulators in TAMs manipulation. Inhibition of NF-κB pathway could achieve both re-polarization M2 TAMs and downregulation the expression of programmed cell death protein 1 (PD-1) ligand 1 (PD-L1) on TAMs to improve the effect of immunotherapies. Here, IMD-0354, inhibitor of NF-κB pathway was loaded in mannose modified lipid nanoparticles (M-IMD-LNP). Then, PD-1 antibody and M-IMD-LNP were co-loaded in matrix metalloproteinase 2 (MMP2) responsive and tumor target nanogels (P/ML-NNG). P/ML-NNG could co-deliver drugs to tumor site, disintegrated by MMP2 and release drugs to different targets. Evaluation of PD-1 expression, inhibition of NF-κB pathway, expression of PD-L1 on M2 TAMs and M2 TAMs re-polarization demonstrated that P/ML-NNG could block the PD-1/PD-L1 and NF-κB pathways simultaneously. Evaluation of CD4 + T cells, CD8 + T cells, Tregs, cytokines and antitumor immunity confirmed that IMD-0354 could improve the immunotherapies effectively. Those results provided forceful references for tumor immunetherapy.


Assuntos
Metaloproteinase 2 da Matriz , Macrófagos Associados a Tumor , Humanos , Imunoterapia , NF-kappa B , Microambiente Tumoral
14.
Stem Cells Dev ; 30(17): 843-855, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34148409

RESUMO

Lung aging alters the intrinsic structure of the lung and pulmonary surfactant system and increases the mortality and morbidity due to respiratory diseases in elderly individuals. We hypothesized that lung aging results from an insufficiency of type II alveolar epithelial cells (AECIIs) in the lung tissue. Sirtuin 3 (SIRT3) is a member of the sirtuin family of proteins that promote longevity in many organisms. Increased SIRT3 expression has been linked to an extended life span in humans. Hence, we speculated that the overexpression of SIRT3 may help to ameliorate lung senescence and improve AECII function. AECIIs were isolated from young and old patients with pneumothorax caused by pulmonary bullae. The expression of SIRT3, manganese superoxide dismutase, and catalase, as well as cell function and senescence indicators of young and old AECIIs, was measured before and after SIRT3 overexpression. After SIRT3 overexpression, the aged state of old AECIIs improved, and antiapoptotic activity, proliferation, and secretion were dramatically enhanced. Surfactant protein C (SPC), which is secreted by AECIIs, reduces alveolar surface tension, repairs the alveolar structure, and regulates inflammation. SPC deficiency in patients is associated with increased inflammation and delayed repair. SIRT3 deacetylated forkhead box O3a, thereby protecting mitochondria from oxidative stress and improving cell function and the senescent state of old AECIIs. These findings provide a possible direction for aging-delaying therapies and interventions for diseases of the respiratory system.

15.
Int J Nanomedicine ; 16: 4161-4173, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34168446

RESUMO

Purpose: Specific targeting receptors for efficiently capturing and applicable nanodevice for separating and instant observing of circulating tumour cells (CTC) are critical for early diagnosis of cancer. However, the existing CTC detection system based on epithelial cell adhesion molecule (EpCAM) was seriously limited by low expression and poor specificity of targeting receptors, and not instant observation in clinical application. Methods: Herein, an alternative glypican-3 (GPC3)-based immunomagnetic fluorescent system (C6/MMSN-GPC3) for high-specific isolation and instant observation of CTC from hepatocellular carcinoma (HCC) patients' peripheral blood was developed. The high-specific HCC targeting receptor, GPC3, was employed for improving the sensitivity and accuracy in CTC detection. GPC3 monoclonal antibody (mAb) was linked to immunomagnetic mesoporous silica for specific targeting capture and separate CTC, and fluorescent molecule coumarin-6 (C6) was loaded for instant detection of CTC. Results: The cell recovery (%) of C6/MMSN-GPC3 increased in 106 HL-60 cells (from 49.7% to 83.0%) and in whole blood (from 42% to 80.3%) compared with MACS® Beads. In clinical samples, the C6/MMSN-GPC3 could capture more CTC in the 13 cases of HCC patients and the capture efficiency was improved by 83.3%-350%. Meanwhile, the capture process of C6/MMSN-GPC3 was harmless, facilitating for the subsequent culture. Significantly, the C6/MMSN-GPC3 achieved the high-specific isolation and instant observation of CTC from HCC patients' blood samples, and successfully separated CTC from one patient with early stage of HCC (Stage I) and one post-surgery patient, further indicating the potential ability of C6/MMSN-GPC3 for HCC early diagnosis and prognosis evaluation. Conclusion: Our study provides a feasible glypican-3 (GPC3)-based immunomagnetic fluorescent system (C6/MMSN-GPC3) for high-specific isolation and instant observation of HCC CTC.


Assuntos
Carcinoma Hepatocelular/patologia , Separação Celular/instrumentação , Glipicanas/metabolismo , Neoplasias Hepáticas/patologia , Nanotecnologia/instrumentação , Células Neoplásicas Circulantes/patologia , Adulto , Carcinoma Hepatocelular/sangue , Fluorescência , Humanos , Neoplasias Hepáticas/sangue , Masculino , Pessoa de Meia-Idade
16.
Microb Cell Fact ; 20(1): 95, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952256

RESUMO

BACKGROUND: The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the need to develop safe and effective vaccines with a top priority. Multiple vaccine candidates are under development, and several vaccines are currently available. Efforts need to be undertaken to counter the threat of the global COVID-19 pandemic. RESULTS: We generated a Saccharomyces cerevisiae (S. cerevisiae)-based SARS-CoV-2 vaccine, EBY100/pYD1-RBD, in which the full-length receptor binding domain (RBD) of the spike protein of SARS-CoV-2 was expressed on the surface of yeast. Mice vaccinated orally with unadjuvanted EBY100/pYD1-RBD could produce significant humoral and mucosal responses as well as robust cellular immune responses. Notably, EBY100/pYD1-RBD elicited a mixed Th1/Th2-type cellular immune response with a Th1-biased immune response in a mouse model. CONCLUSIONS: Our findings highlight the importance of the RBD as a key target to design and develop vaccines against SARS-CoV-2 and provide evidence of oral administration of a S. cerevisiae-based SARS-CoV-2 vaccine eliciting significant immune responses. Most importantly, the S. cerevisiae surface display system can serve as a universal technology platform and be applied to develop other oral viral or bacterial vaccines.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Imunidade Celular , Saccharomyces cerevisiae , Glicoproteína da Espícula de Coronavírus/imunologia , Administração Oral , Animais , Sítios de Ligação , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Feminino , Imunidade Humoral , Imunidade nas Mucosas , Camundongos , Camundongos Endogâmicos BALB C
17.
ACS Appl Mater Interfaces ; 13(19): 22213-22224, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-33955746

RESUMO

Lymph nodes are the main sites for immune activation and surveillance. Effective delivery of immunomodulators into lymph nodes to trigger antitumor immunity is essential for cancer treatment. Here, we propose a lymph node delivery strategy to modulate the immune response by activating cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells simultaneously. Novel pH/redox dual-sensitive micelles were prepared using poly(l-histidine)-poly(ethylene glycol) (PLH-PEG) as a skeleton, which can effectively deliver immunomodulators to the lymph nodes due to their suitable particle size. At 48 h after subcutaneous injection, the accumulation efficiency in lymph nodes increased 8.12-fold compared with the control group. Subsequently, Trp2/CpG-coloaded pH/redox dual-sensitive micelles (Trp2/CpG-NPs) acted on antigen-presenting cells, fully promoting CTL activation through dendritic cell antigen cross-presentation and macrophage repolarization. IL-15-loaded pH/redox dual-sensitive micelles (IL-15-NPs) were developed to activate the killing effect of NK cells by interacting with IL-15 receptors. In the tumor-bearing mice model, this lymph node delivery strategy showed significant antitumor efficiency and the tumor inhibition rate reached 93.76%. Meanwhile, the infiltration of CTLs and NK cells in tumor tissues increased, and the immunosuppressive microenvironment was relieved by the repolarization of macrophages from M2-type to M1-type. Overall, this study highlighted the potential of the lymph node delivery strategy for cancer immunotherapy.


Assuntos
Imunoterapia/métodos , Células Matadoras Naturais/imunologia , Linfonodos/imunologia , Ativação Linfocitária , Neoplasias/terapia , Linfócitos T Citotóxicos/imunologia , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Ensaios Antitumorais Modelo de Xenoenxerto
18.
BMC Cardiovasc Disord ; 21(1): 200, 2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33882833

RESUMO

BACKGROUND: Myocardial ischemia-reperfusion (IR) injury is a damage due to an initial reduction in blood flow to the heart, preventing it from receiving enough oxygen, and subsequent restoration of blood flow through the opening of an occluded coronary artery producing paradoxical harmful effects. The finding of new therapies to prevent IR is of utmost importance. Allicin is a compound isolated from garlic having the ability to prevent and cure different diseases, and a protective effect on the myocardium was also demonstrated. Therefore, the aim of this study was to evaluate the in vitro protective effect of Allicin against myocardial IR injury on cardiomyocytes. METHODS: We established an in vitro hypoxia-reoxygenation (HR) model of primary porcine cardiomyocytes to simulate myocardial IR injury. Primary porcine cardiomyocytes were extracted from Mini-musk swines (1 day old). After a period of adaptation of at least 2-3 days, cardiomyocytes in good condition were selected and randomly divided into control group (normal oxygen for 5 h), HR group (2 h of hypoxia/3 h of reoxygenation), and HR + Allicin group (hypoxia/reoxygenation + Allicin treatment). RESULTS: After the induction of hypoxia/reoxygenation, Allicin treatment enhanced the cell viability. Moreover, Allicin treatment resulted in a reduction of apoptosis from 13.5 ± 1.2% to 6.11 ± 0.15% compared with the HR group (p < 0.05), and the apoptosis related proteins were regulated as well, with a decreased expression of Bax, cleaved caspase-3 and cytosolic cytochrome C and an increase in Bcl-2 expression in the HR + Allicin group (all p < 0.01). Pro-inflammatory cytokines, such as interleukin-6 and tumor necrosis factor alpha were down-regulated by the treatment with Allicin (both p < 0.01). In addition, it significantly decreased intracellular reactive oxygen species generation (p < 0.01) and reduced the loss of mitochondrial membrane potential (p < 0.01). Furthermore, the expression of PPARγ coactivator-1α and endothelial nitric oxide synthase was up-regulated (both p < 0.01), while the expression of Endothelin-1, hypoxia inducing factor-1α and transforming growth factor beta was down-regulated (all p < 0.01) by Allicin treatment. CONCLUSIONS: These results suggested that Allicin protected the cardiomyocytes against HR damage by reducing apoptosis, inflammation and mitochondrial injury, thus providing a basis for its potential use in the treatment of myocardial IR.


Assuntos
Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Dissulfetos/farmacologia , Mediadores da Inflamação/metabolismo , Inflamação/prevenção & controle , Mitocôndrias Cardíacas/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Ácidos Sulfínicos/farmacologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Hipóxia Celular , Células Cultivadas , Citocinas/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Suínos , Porco Miniatura
19.
J Cereb Blood Flow Metab ; 41(10): 2510-2523, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33818184

RESUMO

Nicotinamide phosphoribosyltransferase (NAMPT) is the key enzyme for the synthesis of nicotinamide adenine dinucleotide (NAD) in the salvaging pathway. Though NAMPT inhibitors such as FK866 were originally developed as anti-cancer drugs, they also display neuroprotective effects. Here we show that the administration of FK866 at 0.5 mg/kg (ip, qod) for four weeks, i.e., ∼1% of the dose used for the treatment of cancer, significantly alleviates the aging-induced impairment of cognition and locomotor activity. Mechanistically, FK866 enhanced autophagy, reduced protein aggregation, and inhibited neuroinflammation indicated by decreasing TNFα, IL-6, GFAP, and Iba1 levels in the aged mouse brain. Though FK866 did not affect the total NAD and nicotinamide mononucleotide (NMN) levels in the mouse brain at the dose we used, FK866 increased nicotinamide (NAM) level in the young mouse brain and decreased NAM level in the aged mouse brain. On the other hand, FK866 did not affect the serum glucose, cholesterol, and triglyceride of young and aged mice and exhibited no effects on the various indices of young mice. Thus, the NAMPT inhibitor can be repurpose to counteract the cognitive impairment upon aging. We also envision that NAMPT inhibitor can be used for the treatment of age-related neurodegenerative diseases.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Nicotinamida Fosforribosiltransferase/antagonistas & inibidores , Envelhecimento , Animais , Feminino , Humanos , Camundongos
20.
Acta Haematol ; 144(1): 44-47, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32653886

RESUMO

BACKGROUND: Previous studies had shown that glycosaminoglycan (GAG) from Urechis unicinctus exerts an obvious antiplatelet aggregation effect. OBJECTIVE: This study aims to investigate the effects of GAG from Urechis unicinctus on ADP-induced platelet calcium and membrane glycoprotein expressions in rats. METHODS: Fura-2/AM fluorescence probe was used to measure intracytosolic free-calcium concentration ([Ca2+]i) of platelets and calculate platelet calcium influx and release concentrations. Flow cytometry was used to detect the expressions of platelet membrane glycoproteins GPIIb/IIIa (PAC-1) and P-selectin (CD62P) in rats. RESULTS: The results showed that the GAG from U. unicinctus significantly inhibited the release of platelet calcium (p < 0.01) and the expressions of platelet GPII b/IIIa and P-selectin (p < 0.01) induced by ADP in rats but had no significant effect on the influx of platelet calcium (p > 0.01). CONCLUSIONS: This study indicated that GAG may inhibit platelet activation and aggregation by reducing the release of Ca2+ and ADP-induced expression of platelet membrane glycoprotein in rats.


Assuntos
Difosfato de Adenosina/farmacologia , Produtos Biológicos/farmacologia , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Cálcio/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Glicosaminoglicanos/farmacologia , Glicoproteínas da Membrana de Plaquetas/genética , Poliquetos/química , Animais , Produtos Biológicos/química , Sinalização do Cálcio , Citometria de Fluxo , Glicosaminoglicanos/química , Íons/metabolismo , Glicoproteínas da Membrana de Plaquetas/metabolismo , Ratos
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