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1.
Adv Mater ; : e2100843, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34240472

RESUMO

Plastics are now indispensable in daily lives. However, the pollution from plastics is also increasingly becoming a serious environmental issue. Recent years have seen more sustainable approaches and technologies, commonly known as upcycling, to transform plastics into value-added materials and chemical feedstocks. In this review, the latest research on upcycling is presented, with a greater focus on the use of renewable energy as well as the more selective methods to repurpose synthetic polymers. First, thermal upcycling approaches are briefly introduced, including the redeployment of plastics for construction uses, 3D printing precursors, and lightweight materials. Then, some of the latest novel strategies to deconstruct condensation polymers to monomers for repolymerization or introduce vulnerable linkers to make the plastics more degradable are discussed. Subsequently, the review will explore the breakthroughs in plastics upcycling by heterogeneous and homogeneous photocatalysis, as well as electrocatalysis, which transform plastics into more versatile fine chemicals and materials while simultaneously mitigating global climate change. In addition, some of the biotechnological advances in the discovery and engineering of microbes that can decompose plastics are also presented. Finally, the current challenges and outlook for future plastics upcycling are discussed to stimulate global cooperation in this field.

2.
Helicobacter ; : e12832, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34231948

RESUMO

OBJECTIVE: To evaluate the effectiveness of using WeChat platform to manage the patients with H. pylori infection. METHODS: 566 patients were randomly divided into two groups: The control group was treated with traditional management method, and the experimental group established WeChat group and implemented the informatization management. The two groups were given a unified plan to eradicate H. pylori. After the treatment, the C14 breath test was reexamined. The follow-up rate and H. pylori eradication rate of the two groups were counted. RESULTS: In the experimental group, 289 patients were enrolled and 271 patients were followed up. The follow-up rate was 93.8%. The number of H. pylori-negative patients was 244, and the eradication rate was 90.0%. In the control group, 277 patients were enrolled in the study, and 215 patients were followed up. The follow-up rate was 77.6%. 169 cases of H. pylori-negative conversion were found, and the eradication rate was 78.6%. CONCLUSION: Through WeChat management, the medication adherence, regular follow-up, and H.pylori infection eradication rate of the patients with H.pylori infection in the experimental group were better than that in control group, during the treatment of eradicating H.pylori, and the difference was statistically significant.

3.
Vet Res ; 52(1): 104, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34256834

RESUMO

In bovine mammary epithelial cells (BMECs), a cascade of inflammatory reactions induced by lipopolysaccharide (LPS) has been shown to result in cell injury and apoptosis. The present study aims to reveal the protective effect of ferulic acid (FA) on LPS-induced BMEC apoptosis and explore its potential molecular mechanisms. First, we showed that FA had low cytotoxicity to BMECs and significantly decreased cell apoptosis and the proinflammatory response induced by LPS. Next, FA blocked LPS-induced oxidative stress by restoring the balance of the redox state and inhibiting mitochondrial dysfunction, the main contributor to LPS-induced apoptosis and ROS generation. Furthermore, the relief of inflammation and redox disturbance in the FA preconditioning group were accompanied by weaker NF-κB activation, enhanced Nrf2 activation and maintained cell viability compared to the LPS group. When BMECs were treated with FA alone, we observed that Nrf2 activation was induced before the inhibition of NF-κB activation and that the Keap1-Nrf2 relationship was disturbed. We concluded that FA prevented LPS-induced BMEC apoptosis by reversing the dominant relationship between NF-κB and Nrf2.

4.
ChemSusChem ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34258888

RESUMO

Structural diversity and designability and eco-friendliness make organic electrode materials appealing to next-generation rechargeable batteries. However, most of them show low specific capacity and poor cycling stability, which limited their further application. To develop high-capacity imide-based cathode materials, we design three C 3 -symmetric triimides. Systematic comparisons of these triimides as cathode materials reveal that extending π-conjugation and incorporating multiple redox centers improve the cell performance in term of specific capacity and cycle stability. In particular, a nitrogen-rich heteroaromatic hexaazatrinaphthylene triimide (HATNTI-Pr) with multiple active sites (imide and pyrazine) exhibits high specific capacity. Hybridized with graphene sheets, a HATNTI-Pr-based binder-free cathode delivers a high practical capacity (317 mAh g -1 at 0.1 C), excellent cycling stability (80% retention after 100 cycles) and considerable rate performance (75 mAh g -1 at 5 C). The energy storage mechanism of HATNTI-Pr with up to nine Li + storage ability is investigated.

5.
Int J Nanomedicine ; 16: 4631-4642, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262273

RESUMO

Purpose: Antibiotic-resistant bacteria are pathogens that have emerged as a serious public health risk. Thus, there is an urgent need to develop a new generation of anti-bacterial materials to kill antibiotic-resistant bacteria. Methods: Nanosilver-decorated mesoporous organosilica nanoparticles (Ag-MONs) were fabricated for co-delivery of gentamicin (GEN) and nanosilver. After investigating the glutathione (GSH)-responsive matrix degradation and controlled release of both GEN and silver ions, the anti-bacterial activities of Ag-MONs@GEN were systematically determined against several antibiotic-susceptible and antibiotic-resistant bacteria including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. Furthermore, the cytotoxic profiles of Ag-MONs@GEN were evaluated. Results: The GEN-loaded nanoplatform (Ag-MONs@GEN) showed glutathione-responsive matrix degradation, resulting in the simultaneous controlled release of GEN and silver ions. Ag-MONs@GEN exhibited excellent anti-bacterial activities than Ag-MONs and GEN alone via inducing ROS generation, especially enhancing synergetic effects against four antibiotic-resistant bacteria including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. Moreover, the IC50 values of Ag-MONs@GEN in L929 and HUVECs cells were 313.6 ± 15.9 and 295.7 ± 12.3 µg/mL, respectively, which were much higher than their corresponding minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. Conclusion: Our study advanced the development of Ag-MONs@GEN for the synergistic and safe treatment of antibiotic-resistant bacteria.

6.
Am J Hematol ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34265098

RESUMO

The red blood cell (RBC) lifespan is an important physiological indicator of clear significance in clinical research, used for the differential diagnosis of various diseases such as anemia, compensatory phase hemolysis, and polycythemia. The 15 N-glycine labeling technique is the gold standard method for determining RBC lifespans. However, the usefulness of this technique in clinical settings is seriously hindered by the several weeks required to complete the analyses. Levitt's CO breath test is another reliable technique for determining RBC lifespans, with a simpler protocol giving much faster results, making it more useful in clinical applications. To compare the CO breath test and 15 N-glycine labeling technique for measuring the human RBC lifespan. We investigated human RBC lifespans where each subject undertook both the 15 N-glycine labeling technique and the CO breath test. The correlation between the results from these two methods were analyzed. Eight of the ten subjects successfully completed the study. The RBC lifespan values obtained by Levitt's CO breath test were lower than those obtained by the 15 N-glycine labeling technique. The RBC lifespan values determined from the 15 N-glycine labeling technique and the CO breath test were significantly correlated, with a Pearson correlation coefficient of R=0.98 (p<0.05), while the R2 of the linear regression equation was 0.96. The CO breath test as good performance as the 15 N-glycine labelling technique in order to distinguish healthy from haemolysis subjects. The result suggesting that the CO breath test is a reliable method (might be used) for quickly determining human RBC lifespans in clinical applications. This article is protected by copyright. All rights reserved.

7.
Exp Neurol ; : 113812, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34274327

RESUMO

Expression of CREB-regulated transcription coactivator 1 (CRTC1) in the hippocampus is impaired in Alzheimer's disease (AD). However, CRTC1 related mechanisms associated with long-term synaptic plasticity impairment and cognitive decline in the onset of AD are unknown. In this study, electrophysiological recordings indicated that lentivirus-mediated CRTC1 overexpression effectively ameliorates suppression of late-phase long-term potentiation (L-LTP) in rat hippocampal slices treated with oligomeric amyloid ß(1-42) peptides (oAß42) (200 nM). In addition, application of oAß42 and genetic knockdown of CRTC1 by lentivirus-mediated CRTC1-shRNA inhibits L-LTP, whereas their combination does not further impair L-LTP. Brain-derived neurotrophic factor (BDNF), an important downstream protein confers protection of CRTC1 overexpression against oAß42-induced L-LTP impairment as shown by administration of K252a (200 nM) and TrkB-FC (20 µg/mL). Furthermore, behavioral and western blotting analyses showed that CRTC1 overexpression reverses oAß42-induced hippocampal-dependent cognitive deficits, downregulation of CRTC1 and BDNF expression. Notably, CRTC1-shRNA directly elicits cognitive deficits. In summary, these findings show that hippocampal CRTC1 signaling is affected by soluble oAß, and CRTC1-BDNF pathway is involved in hippocampal L-LTP impairment and memory deficits induced by oAß42.

8.
Small ; : e2101741, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34288410

RESUMO

Recovery from bone, osteochondral, and cartilage injuries/diseases has been burdensome owing to the damaged vasculature of large defects and/or avascular nature of cartilage leading to a lack of nutrients and supplying cells. However, traditional means of treatment such as microfractures and cell-based therapy only display limited efficacy due to the inability to ensure cell survival and potential aggravation of surrounding tissues. Exosomes have recently emerged as a powerful tool for this tissue repair with its complex content of transcription factors, proteins, and targeting ligands, as well as its unique ability to home in on target cells thanks to its phospholipidic nature. They are engineered to serve specialized applications including enhancing repair, anti-inflammation, regulating homeostasis, etc. via means of physical, chemical, and biological modulations in its deriving cell culture environments. This review focuses on the engineering means to functionalize exosomes for bone, osteochondral, and cartilage regeneration, with an emphasis on conditions such as osteoarthritis, osteoporosis, and osteonecrosis. Finally, future implications for exosome development will be given alongside its potential combination with other strategies to improve its therapeutic efficacy in the osteochondral niche.

9.
Cell Death Dis ; 12(7): 680, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226519

RESUMO

It has been recently reported that CD38 expressed on tumor cells of multiple murine and human origins could be upregulated in response to PD-L1 antibody therapy, which led to dysfunction of tumor-infiltrating CD8+ T immune cells due to increasing the production of adenosine. However, the role of tumor expressed-CD38 on neoplastic formation and progression remains elusive. In the present study, we aimed to delineate the molecular and biochemical function of the tumor-associated CD38 in lung adenocarcinoma progression. Our clinical data showed that the upregulation of tumor-originated CD38 was correlated with poor survival of lung cancer patients. Using multiple in vitro assays we found that the enzymatic activity of tumor expressed-CD38 facilitated lung cancer cell migration, proliferation, colony formation, and tumor development. Consistently, our in vivo results showed that inhibition of the enzymatic activity or antagonizing the enzymatic product of CD38 resulted in the similar inhibition of tumor proliferation and metastasis as CD38 gene knock-out or mutation. At biochemical level, we further identified that cADPR, the mainly hydrolytic product of CD38, was responsible for inducing the opening of TRPM2 iron channel leading to the influx of intracellular Ca2+ and then led to increasing levels of NRF2 while decreasing expression of KEAP1 in lung cancer cells. These findings suggested that malignant lung cancer cells were capable of using cADPR catalyzed by CD38 to facilitate tumor progression, and blocking the enzymatic activity of CD38 could be represented as an important strategy for preventing tumor progression.

10.
Food Funct ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34251007

RESUMO

With the increasing incidence of type 2 diabetes, it is imperative to identify how to effectively prevent or treat this disease. Studies have shown that some lactic acid bacteria can improve type 2 diabetes with almost no side effects. Therefore, in this experimental study, we explored the preventive and therapeutic effects of Lactobacillus fermentum TKSN041 (L. fermentum TKSN041) on streptozotocin-induced type 2 diabetes in rats. The results showed that L. fermentum TKSN041 could reduce the amount of water intake, reduce weight loss, and control the increase in the fasting blood glucose level of diabetic rats. The organ index and tissue section results showed that L. fermentum TKSN041 could reduce the damage caused by diabetes to the liver, kidney, spleen, pancreatic, and brain tissue. Furthermore, L. fermentum TKSN041 decreased the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL), aminotransferase (AST), alanine aminotransferase (ALT), glycated serum proteins (GSP), malondialdehyde (MDA), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), and endothelin 1 (ET-1) in serum and increased the serum levels of high-density lipoprotein cholesterol (HDL) and interleukin 10 (IL-10). Finally, L. fermentum TKSN041 up-regulated the mRNA and protein expressions of NF-kappa-B inhibitor-α (IκB-α), AMP-activated protein kinase (AMPK), insulin receptor substrate-1 (IRS-1), liver kinase B1 (LKB1), and glucose transporter 4 (GLUT4) and down-regulated those of nuclear factor-κBp65 (NFκB-p65) and tumor necrosis factor alpha (TNF-α). Furthermore, LF-TKSN041 up-regulated the mRNA expressions of peroxisome proliferator-activated receptor γ (PPAR-γ) and down-regulated neuropeptide Y (NPY), sterol regulatory element-binding protein-1 (SREBF-1), and vascular endothelial growth factor (VEGF). These results suggest that L. fermentum TKSN041 may be a useful intervention factor for the prevention or treatment of type 2 diabetes induced by STZ. Clinical trials are needed to further demonstrate its effectiveness.

11.
Cell Signal ; : 110084, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34271086

RESUMO

Inflammation and pyroptosis play a deleterious role in cardiac dysfunction after myocardial infarction (MI). NLRP3/caspase-1 is a well-established axis in pyroptosis and inflammation. In this study, we examined the effects of TN-C on pyroptosis through NLRP3 is unclear. We constructed 18 TN-C-knockout and 38 WT male mice model and divided into WT sham (n = 16), WT MI (n = 22), TNKO sham (n = 6), TNKO MI (n = 12). Elisa, immunostaining, TTC, qPCR, CCK8, flow cytometry, and western blot, echocardiographic, TUNEL staining technologies were applied. Here, we found a positive correlation between TN-C and NLRP3 in heart tissue via the GEPIA database (r = 0.52, p < 0.05). The findings indicate that TN-C was elevated and peaked on the fifth day after MI. TN-C deficiency alleviated cardiac dysfunction (LVEF, FS, LVIDd, and LVIDs) and cardiomyocyte death. Though the intracellular levels of pyroptosis-related cytokine caspase-1, cleaved caspase-1, NLRP3, IL-18, IL-1ß were upregulated both in MI and H2O2 stimulation, knockout of TN-C resisted such injury and alleviated cardiac pyroptosis, which further decreased IL-6, TNF-α, MCP-1 expression. TN-C knockdown inhibited TLR4 expression, reduces the release of downstream factors by inactivating the TLR4/NF-kB pathway, while protects the cardiomyocytes. And TLR4 inhibitor TAK-242 significantly reduced NLRP3 expression levels after MI. We demonstrated for the first time a direct link between MI-induced TN-C upregulation and caspase-1-dependent cardiomyocyte pyroptosis, a process mediated, at least in part, by TLR4/NF-kB/NLRP3 and IL-18, IL-1ß signaling pathways. These findings provide new insights into the role of TN-C in post-MI cardiomyocytes' pyroptosis and inflammation.

12.
Ann Hematol ; 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34269836

RESUMO

The presence of paroxysmal nocturnal hemoglobinuria (PNH) clones in aplastic anemia (AA) suggests immunopathogenesis, but when and how PNH clones emerge and proliferate are unclear. Hepatitis-associated aplastic anemia (HAAA) is a special variant of AA, contrarily to idiopathic AA, in HAAA the trigger for immune activation is clearer and represented by the hepatitis and thus serves as a good model for studying PNH clones. Ninety HAAA patients were enrolled, including 61 males and 29 females (median age 21 years). Four hundred three of idiopathic AA have been included as controls. The median time from hepatitis to cytopenia was 50 days (range 0-180 days) and from cytopenia to AA diagnosis was 26 days (range 2-370 days). PNH clones were detected in 8 HAAA patients (8.9%) at diagnosis and in 73 patients with idiopathic AA (IAA) (18.1%). PNH cells accounted for 4.2% (1.09-12.33%) of red cells and/or granulocytes and were more likely to be detected in patients with longer disease history and less severe disease. During follow-up, the cumulative incidence of PNH clones in HAAA increased to 18.9% (17/90). Nine HAAA patients newly developed PNH clones, including six immunosuppressive therapy (IST) nonresponders. The clone size was mostly stable during follow-up, and only 2 of 14 patients showed increased clone size without proof of hemolysis. In conclusion, PNH clones were infrequent in newly diagnosed HAAA, but their frequency increased to one that was similar to the IAA frequency during follow-up. These results suggest that the PNH clone selection/expansion process is dynamic and takes time to establish, confirming that retesting for PNH clones during follow-up is crucial.

13.
Nat Commun ; 12(1): 4195, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: covidwho-1301166

RESUMO

SARS-CoV-2 can infect many domestic animals, including dogs. Herein, we show that dog angiotensin-converting enzyme 2 (dACE2) can bind to the SARS-CoV-2 spike (S) protein receptor binding domain (RBD), and that both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells. We solved the crystal structure of RBD in complex with dACE2 and found that the total number of contact residues, contact atoms, hydrogen bonds and salt bridges at the binding interface in this complex are slightly fewer than those in the complex of the RBD and human ACE2 (hACE2). This result is consistent with the fact that the binding affinity of RBD to dACE2 is lower than that of hACE2. We further show that a few important mutations in the RBD binding interface play a pivotal role in the binding affinity of RBD to both dACE2 and hACE2. Our work reveals a molecular basis for cross-species transmission and potential animal spread of SARS-CoV-2, and provides new clues to block the potential transmission chains of this virus.

14.
Nat Commun ; 12(1): 4195, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234119

RESUMO

SARS-CoV-2 can infect many domestic animals, including dogs. Herein, we show that dog angiotensin-converting enzyme 2 (dACE2) can bind to the SARS-CoV-2 spike (S) protein receptor binding domain (RBD), and that both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells. We solved the crystal structure of RBD in complex with dACE2 and found that the total number of contact residues, contact atoms, hydrogen bonds and salt bridges at the binding interface in this complex are slightly fewer than those in the complex of the RBD and human ACE2 (hACE2). This result is consistent with the fact that the binding affinity of RBD to dACE2 is lower than that of hACE2. We further show that a few important mutations in the RBD binding interface play a pivotal role in the binding affinity of RBD to both dACE2 and hACE2. Our work reveals a molecular basis for cross-species transmission and potential animal spread of SARS-CoV-2, and provides new clues to block the potential transmission chains of this virus.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , SARS-CoV-2/metabolismo , Enzima de Conversão de Angiotensina 2/química , Animais , Sítios de Ligação , Linhagem Celular , Cricetinae , Cristalografia por Raios X , Cães , Células HeLa , Humanos , Mutação , Ligação Proteica , Domínios Proteicos , SARS-CoV-2/genética , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do Vírus
15.
Environ Pollut ; 289: 117710, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34243057

RESUMO

Puberty is a critical period for growth and development. This period is sensitive to external stimuli, which ultimately affects the development of nerves and the formation of social behaviour. 17ß-Trenbolone (17ß-TBOH) is an endocrine disrupting chemicals (EDCs), which had been widely reported in aquatic vertebrates. But there is little known about the effects of 17ß-TBOH on mammals, especially on adolescent neurodevelopment. In this study, we found that 17ß-TBOH acute 1 h exposure can cause the activation of the dopamine circuit in pubertal male balb/c mice. At present, there is little known about the effects of puberty exposure of endocrine disruptors on these neurons/nerve pathways. Through a series of behavioural tests, exposure to 80 µgkg-1 d-1 of 17ß-TBOH during adolescence increased the anxiety-like behaviour of mice and reduced the control of wheel-running behaviour and the response of social interaction behaviour. The results of TH immunofluorescence staining showed that exposure to 17ß-TBOH reduced dopamine axon growth in the medial prefrontal cortex (mPFC). In addition, the results of real-time PCR showed that exposure to 17ß-TBOH not only down-regulated the expression of dopamine axon development genes, but also affected the balance of excitatory/inhibitory signals in mPFC. In this research, we reveal the effects of 17ß-TBOH exposure during adolescence on mammalian behaviour and neurodevelopment, and provide a reference for studying the origin of adolescent diseases.

16.
Rev Sci Instrum ; 92(5): 054702, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34243348

RESUMO

A transportable fountain clock with high reliability is important for high-precision time-frequency measurements. Because of its relatively small cold atoms' collision frequency shift and ease of attaining high quantum state preparation efficiency, the rubidium atomic fountain clock has an indicated higher stability and reliability. This paper reports the design and operation of a transportable rubidium atomic fountain clock developed by the Shanghai Institute of Optical and Fine Mechanics, Chinese Academy of Science. After being transported more than 1000 km from Shanghai to the Changping Campus of the National Institute of Metrology, China, the optical platform and other hardware of the fountain clock did not need to be adjusted. The rubidium fountain clock maintained a stability of 4.0 × 10-13τ1/2, reaching 5.0 × 10-16 at 300 000 s. After transportation, the rubidium fountain clock and a cesium fountain clock (NIM5) were operated together against the reference frequency of a hydrogen maser. In three separate operating periods, over a total of nearly three months, the average frequency repeatability of the rubidium fountain was less than 3.8 × 10-15.

17.
Health Commun ; : 1-8, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34251913

RESUMO

Ineffective identity construction of crowd-funders for medical events is a major factor blocking donations from arriving in time to help patients in need. There is a dearth of report on the discursive veins of identity construction in a web-based crowd-funding scenario in Eastern setting, such as in China. This is the first Chinese study aimed to discursively observe, analyze and evaluate identity construction of crowd-funders in online fundraising setting. Content and discourse analyses were employed, with focus on linguistic and interactional dimensions of 500 pieces of online fundraisers' personal statements (collected from https://www.qschou.com). Findings indicate that three different types of fundraisers' identities (as a family member/ a patient/ the disadvantaged) were constructed through discursive strategies oriented toward ethos, expertise and emotion respectively. The findings are conducive to offering online help-seekers an array of identity-motivated discursive strategies to make more prospective backers engage in a medical donative event. Results highlight that crowd-funders need support and training to obtain the expected amount of donation, focusing on enhancing the rhetoric toward sincerity, honesty and morality.

18.
Regul Toxicol Pharmacol ; 124: 104999, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34242706

RESUMO

Tea tree oil (TTO) is a popular topical use to treat skin infections. However, its poor aqueous solubility and stability have substantially limited its widespread application, including oral administration that might be therapeutic for enteric infections. In this study, mechanical ultrasonic methods were used to prepare TTO nanoemulsion (nanoTTO) with a mean droplet diameter of 161.80 nm ± 3.97, polydispersity index of 0.21 ± 0.01, and zeta potential of -12.33 ± 0.72 mV. The potential toxicity of nanoTTO was assessed by studying the oral median lethal dose (LD50) and repeated 28-day oral toxicity to provide a reference for in vivo application. Results showed that nanoTTO had no phase separation under a centrifugation test and displayed good stability during storage at -20, 4 and 25 °C over 60 days. Repeated-dose 28-day oral toxicity evaluation revealed no significant effects on growth and behavior. Assessments of hematology, clinical biochemistry, and histopathology indicated no obvious adverse effects in mice at 50, 100 and 200 mg/mL. These data suggest that nanoTTO can be considered a potential antimicrobial agent by oral administration due to its inhibitory effect on bacteria and relatively lower toxicity.

19.
J Exp Clin Cancer Res ; 40(1): 218, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193219

RESUMO

BACKGROUND: Liver cancer stem cells (LCSCs) play key roles in the metastasis, recurrence, and chemotherapeutic resistance of hepatocellular carcinoma (HCC). Our previous research showed that the POSTN gene is closely related to the malignant progression and poor prognosis of HCC. This study aimed to elucidate the role of POSTN in generating LCSCs and maintaining their stemness as well as the underlying mechanisms. METHODS: Human HCC tissues and matched adjacent normal tissues were obtained from 110 patients. Immunohistochemistry, western blotting (WB), and RT-PCR were performed to detect the expression of POSTN and stemness factors. The roles of transforming growth factor (TGF)-ß1 and AP-2α in the POSTN-induced stemness transformation of HCC cells were explored in vitro and in vivo using LCSCs obtained by CD133+ cell sorting. RESULTS: The high expression of POSTN was correlated with the expression of various stemness factors, particularly CD133, in our HCC patient cohort and in TCGA and ICGC datasets. Knockdown of POSTN expression decreased the abilities of HCC cell lines to form tumours in xenograft mouse models. Knockdown of POSTN expression also suppressed cell viability and clone formation, invasion, and sphere formation abilities in vitro. Knockdown of AP-2α attenuated the generation of CD133+ LCSCs and their malignant behaviours, indicating that AP-2α was a critical factor that mediated the POSTN-induced stemness transformation and maintenance of HCC cells. The role of AP-2α was verified by using a specific αvß3 antagonist, cilengitide, in vitro and in vivo. Activation of POSTN could release TGFß1 from the extracellular matrix and initiated POSTN/TGFß1 positive feedback signalling. Furthermore, we found that the combined use of cilengitide and lenvatinib suppressed the growth of HCC cells with high POSTN expression more effectively than the use of lenvatinib alone in the patient-derived xenograft (PDX) mouse model. CONCLUSIONS: The POSTN/TGFß1 positive feedback pathway regulates the expression of stemness factors and the malignant progression of HCC cells by regulating the transcriptional activation of AP-2α. This pathway may serve as a new target for targeted gene therapy in HCC.

20.
J Immunol Res ; 2021: 9947884, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34195300

RESUMO

Preeclampsia, a multisystem disorder in pregnant women, is diagnosed by onset of new hypertension, proteinuria, or organ damage. Antiangiogenic factors, such as soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng), are long known to be involved in preeclampsia. However, the role of maternal immune system and inflammation in promotion of preeclampsia has lately been a subject of immense interest. Link between maternal inflammation and preeclampsia is not well established. Furthermore, whether cigarette smoke promotes inflammation and also promotes severity of preeclampsia remains an open question. We herein investigated correlation of established inflammation signatures in the plasma and placental tissue from cohorts of preterm preeclampsia (PPE) and preterm pregnancies (control) with or without smoking history. Besides confirming increased levels of Flt1 and Eng in preeclampsia, we also observed an increase in various mediators of maternal inflammation in women with PPE compared to preterm cohort. Increased IL-6, IL-35, and TNF-α and reduced IL-10 in serum and higher MMP-12, TLR4, HMGB-1, and iNOS and lower Foxp3, CD56 transcripts in placental tissues of PPE compared to preterm pregnancies indicate an association of preterm preeclampsia with stark imbalance in maternal immune system and signatures of inflammation. Smoker PPE cohorts showed highest inflammatory signatures including statistically significant increase for many signatures compared to other cohorts. Together, these results provide evidence for association of inflammation with PPE and strong correlation of smoking with inflammatory signatures in PPE.

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