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1.
J Mater Chem B ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32037408

RESUMO

Using Chitosan/PEO as the shell and PCL as the core, chitosan-polyethylene oxide/polycaprolactone nanofibrous mats were prepared successfully by coaxial electrospinning for co-load and sequential co-delivery of two drugs. Herein, lidocaine hydrochloride (Lid), used for pain relief, was added to the shell, and curcumin (Cur), an anti-inflammatory agent, was introduced into the core. Sodium bicarbonate (SB) was also added to the core layer to provide wound microenvironment sensitivity. Under acidic conditions, Lid was released due to the formation of -NH3+ by protonation of -NH2 on the chitosan molecular chains. At the same time, SB reacted with hydrogen ions to generate CO2, and many holes were generated on the surface of the fibers, providing more discharge paths for Cur release. Additionally, both Lid in the shell layer and Cur in the core layer exhibited acidic pH (∼5.4)-responsive release profiles. Moreover, a rapid release of Lid and a sustained release of Cur were observed to provide the immediate effects of analgesia and long-term antibacterial activity in the process of wound healing. Furthermore, after 48 h incubation, the mats showed continuous and excellent antibacterial performance against E. coli and S. aureus. The results of blood coagulation showed that the mats could achieve rapid hemostasis in the early stage of wound formation. Hemolytic and cytotoxicity evaluation also revealed that the mats had excellent hemocompatibility and cytocompatibility. Therefore, this study has made invaluable contributions to the design of a dual-drug-loaded dressing with microenvironment-responsive and sequential release properties towards wound care.

2.
Angiology ; : 3319719896472, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32013536

RESUMO

C-reactive protein (CRP) and high-sensitivity CRP (hsCRP), along with a series of hematological indices, platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), mean platelet volume (MPV), platelet distribution width (PDW), and red blood cell distribution width (RDW), are regarded to be related to the incidence of no-reflow or slow flow. Clinical studies were retrieved from the electronic databases of PubMed, EMBASE, Google Scholar, Clinical Trials, and science direct from their inception to August 24, 2019. A total of 21 studies involving 7403 patients were included in the meta-analysis. Pooled analysis results revealed patients with higher hsCRP (odds ratio [OR] = 1.03, 95% confidence interval [CI], 1.01-1.05, P = .006), hsCRP (OR = 1.04, 95% CI: 1.0-1.08, P = .012), NLR (OR = 1.23, 95% CI: 1.11-1.37, P < .0001), PLR (OR = 1.13, 95% CI: 1.07-1.20, P < .0001), and MPV (OR = 2.13, 95% CI: 1.57-2.90, P < .0001) all exhibited significantly higher no-reflow incidence, but there was no significant association between no-reflow risk and RDW or PDW. Patients with higher CRP/hsCRP also performed higher rate of slow flow (OR = 1.06, 95% CI: 1.01-1.11, P = .018). Preangiographic CRP/hsCRP could independently predict no-reflow and slow flow. Moreover, some hematological indices are associated with no-flow.

3.
BMC Cardiovasc Disord ; 20(1): 40, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000667

RESUMO

BACKGROUND: Endothelial dysfunction may play a key role in non-obstructive coronary artery atherosclerosis. Our study aimed to evaluate the vascular endothelial function and its influencing factors in patients with non-obstructive coronary artery atherosclerosis. METHODS: A total of 131 consecutive patients with non-obstructive coronary artery atherosclerosis were enrolled. Flow-mediated dilatation (FMD) was measured at baseline and 1-year follow-up. Endothelial progenitor cells (EPCs) were counted by staining the fasting venous blood with antibodies against CD34 and vascular endothelial growth factor receptor 2. RESULTS: Systolic blood pressure, pulse pressure and the levels of HbA1c in participants with baseline FMD < 6% (n = 65) were significantly higher than those with baseline FMD ≥ 6% (n = 66). Baseline FMD was negatively associated with EPC counts (r = - 0.199, P < 0.05) and systolic blood pressure (r = - 0.315, P < 0.01). The 1-year FMD was significantly increased compared to the baseline FMD [(9.31 ± 5.62) % vs (7.31 ± 5.26) %, P < 0.001]. Independent predictors of FMD improvement included elevated EPC counts (OR = 1.104, 95% CI: 1.047-1.165, P < 0.001) and decreased levels of serum creatinine (OR = 0.915, 95% CI: 0.843-0.993, P = 0.034). CONCLUSIONS: Family history of premature cardiovascular diseases, hypertension, elevated systolic pressure, and HbA1c > 6.5% are independent risk factors for endothelial dysfunction in non-obstructive atherosclerotic patients. Elevated peripheral blood EPC counts and decreased levels of serum creatinine are independent predictors of endothelial function improvement.

4.
Cancer Lett ; 475: 22-33, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32014457

RESUMO

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related mortality. Artemisinin (ART) and SOMCL-14-221 (221), a spirobicyclic analogue of ART, have been reported to inhibit the proliferation of A549 cells with unclear underlying mechanism. In the present study, we validated that both ART and 221 inhibited the proliferation and migration of NSCLC cells and the growth of A549 xenograft tumors without appreciable toxicity. The proteomic data revealed proteins upregulated in ART and 221 groups were involved in "response to endoplasmic reticulum stress" and "amino acid metabolism". Asparagine synthetase (ASNS) was identified as a key node protein in these processes. Interestingly, knockdown of ASNS improved the antitumor potency of ART and 221 in vitro and in vivo, and treatments with ART and 221 disordered the amino acid metabolism of A549 cells. Moreover, ART and 221 activated ER stress, and inhibition of ER stress abolished the anti-proliferative effects of ART and 221. In conclusion, this study demonstrates that ART and 221 suppress tumor growth by triggering ER stress, and the inhibition of ASNS enhances the antitumor activity of ART and 221, which provides new strategy for drug combination therapy.

5.
Curr Pharm Des ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32066357

RESUMO

In animals, the gastrointestinal microbiota is reported to play a major role in digestion, nutrient absorption and the release of energy through metabolism of food. Therefore, the microbiota may be a factor in the links between diet and enteric diseases and oxidative stress. The gut microbial composition and concentration are affected by diet throughout the lifetime of an animal, and respond rapidly and efficiently to dietary alterations, in particular to the use of prebiotics. Prebiotics, which play an important role in mammalian nutrition, are defined as dietary ingredients that lead to specific changes in both the composition and activity of the gastrointestinal microbiota through suppressing the proliferation of pathogens and in modifying the growth of beneficial microorganisms in the host intestine. A review of the evidence suggests possible beneficial effects of prebiotics on host intestinal health, including immune stimulation, gut barrier enhancement and the alteration of the gastrointestinal microbiota, and these effects appear to be dependent on alteration of the bacterial composition and short-chain fatty acid (SCFA) production. The production of SCFAs depends on the microbes available in the gut and the type of prebiotics available. The SCFAs most abundantly generated by gastrointestinal microbiota are acetate, butyrate and propionate, which are reported to have physiological effects on the health of the host. Nowadays, prebiotics are widely used in a range of food products to improve the intestinal microbiome and stimulate significant changes to the immune system. Thus, a diet with prebiotic supplements may help prevent enteric disease and oxidative stress by promoting a microbiome associated with better growth performance. This paper provides an overview of the hypothesis that a combination of ingestible prebiotics, chitosan, fructooligosaccharides and inulin will help relieve the dysbiosis of the gut and the oxidative stress of the host.

6.
Sci Rep ; 10(1): 2639, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060329

RESUMO

Plasma trimethylamine N-oxide (TMAO) is associated with coronary atherosclerotic plaque and cardiovascular disease risk, but associations between gut microbes in acute coronary syndrome (ACS) and post-ST-segment elevation myocardial infarction (post-STEMI) events are unknown. We investigated associations between gut microbial taxa and systemic TMAO levels and the possible TMAO contribution to incident post-STEMI cardiovascular events. PATIENTS AND METHODS: A total of 60 patients, including 30 with unstable angina pectoris (UAP), 30 post-STEMI and 30 healthy controls, were enrolled from June to November 2017. Metagenomic sequencing was performed and TMAO and IL-6 were detected. RESULTS: Minimal discriminators of gut microbial taxa (top 40) distinguished ACS patients from controls. Serum TMAO levels were positively associated with increased abundance of Aerococcaceae, Ruminococcaceae_UCG.005, Ruminococcaceae_UCC.014 and X. Eubacterium_fissicatena, and decreased abundance of Lachnospiraceae_FCS020 (P < 0.05). Elevated serum TMAO levels correlated independently with ACS (P < 0.05). Risk stratification for incident major adverse cardiovascular events (MACE) improved at one year in patients with serum TMAO levels ≦2.19 µM. Serum interleukin-6 levels were not significantly increased in patients with ACS and post-STEMI MACE. CONCLUSIONS: ACS and incident post-STEMI MACE may be associated with the gut bacteria choline metabolite TMAO. The specific gut microbial taxa identified in association with serum TMAO levels may be potential predictive biomarkers for accurate diagnosis of ACS onset.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32076930

RESUMO

BACKGROUND: Although Takotsubo syndrome (TS) was once considered to be rare and largely benign, it is now recognized to represent a major cause of cardiac morbidity and mortality, especially in ageing women. The biochemical precipitant of attacks of TS is an increase in catecholamine concentrations within the myocardium, engendering inflammatory activation via biased post-receptor signalling at myocardial ß2-adrenoceptor level. Cases of TS have been reported in patients treated with catecholamines, and with antidepressants which limit catecholamine re-uptake. In the current investigation, we sought to delineate the extent and potential impact of this "iatrogenic" form of TS. METHODS/RESULTS: Patients' data from a regional registry of 301 consecutive cases of TS were evaluated after exclusion of patients (n = 20) in whom TS had occurred in association with life threatening extracardiac disease states. A total of 55 (18%) of patients were identified as having antecedent exposure to potentially "iatrogenic" agents (tricyclic antidepressants in 24 cases, ß2-adrenoceptor agonists in 15). Demographics, including proportion of male patients, did not differ significantly between patients with and without "iatrogenic" TS, but plasma concentrations of the catecholamine metabolite normetanephrine tended to be greater (median 1149 pmol/L vs 938 pmol/L; p = 0.03). Long-term survival (median follow-up 3 years) was marginally (p = 0.13) worse for patients with "iatrogenic" TS. CONCLUSION: Potentially iatrogenic precipitation of TS attacks (via iatrogenic elevation of catecholamine levels and ß2-adrenoceptor stimulation) is common, associated with greater elevation of plasma normetanephrine concentrations, and also with a trend towards increased long-term mortality when compared to the remainder of TS patients.

8.
Anal Chem ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32077685

RESUMO

Microplastics (MPs) pollution has drawn increasing concern due to its widespread occurrence and potential risks in the environment. The reliable methods and instruments for fast analysis of microplastics (MPs) less than 5 mm are urgently needed. In this study, a new method based on custom-made portable pyrolysis-mass spectrometry (Pyr-MS) is developed, which enables rapid identification and mass related quantification of MPs. MPs are decomposed in the compact pyrolyzer, then directly analyzed in the portable MS by the chemical fingerprints of polymers including characteristic ions and their special ratio. It avoids the complex extraction and separation procedures of the pyrolysis/ thermogravimetric-gas chromatography-mass spectrometry (Pyr/TGA-GC-MS), realizes the rapid analysis of MPs in 5 minutes, thus can practically apply to a large number of MPs samples. In comparison to fourier transform infrared spectroscopy (FT-IR) and Raman, this method is not limited by the shape, size, and colour of MPs. Four common plastics including polyethylene (PE), polypropylene (PP), polystyrene (PS), and poly (methyl methacrylate) (PMMA) were investigated to verify the feasibility of this method. The environmental MPs samples collected from a beach were successfully identified and quantified, demonstrating the simplicity and practicality of this approach. The influence of plastics aging on the chemical fingerprints and the potential of mixed plastics detection by Pyr-MS are also assessed. The portable Pyr-MS could provide a promising tool for in-field analysis of MPs such as ship-based marine MPs surveys.

9.
Reprod Sci ; 27(1): 152-162, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32046397

RESUMO

Recurrent spontaneous abortion (RSA) is a common health problem that affects 1-5% of women in reproductive age. Plenty of studies have indicated that microRNAs (miRNAs) are involved in the occurrence of miscarriage. MiR-93 has a wide range of functions in mammalian tissues and plays an important role in many diseases especially for cancers. However, it remains unknown whether miR-93 is associated with human RSA. In this report, clinical samples revealed that miR-93 expression was significantly elevated in the villi tissues of RSA patients. Upregulation of miR-93 inhibited human trophoblast cells HTR-8/SVneo cell proliferation, migration, and invasiveness, but promoted cell apoptosis in vitro. Conversely, the downregulation of miR-93 reversed these effects. Bcl-2 like protein 2 (BCL2L2), a potential target gene of miR-93, was inversely correlated with miR-93 expression in the villi of clinical samples. Furthermore, the luciferase reporter system demonstrated that miR-93 directly downregulated the expression of BCL2L2 by binding a specific sequence of its 3'-untranslated region (3'UTR). Collectively, these data strongly suggest that miR-93 regulates trophoblast cell proliferation, migration, invasive, and apoptosis by targeting BCL2L2 expression and is involved in the pathogenesis of RSA.

10.
Environ Int ; 137: 105540, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32032776

RESUMO

The prevalence and accumulation of antibiotic resistance genes (ARGs) were frequently detected in biological wastewater treatment processes, which might cause potential health crisis to human. In present study, the fates of ARGs during two different aerobic granular sludge (AGS) cultivation processes were investigated. The results showed that traditional AGS (T-AGS) cultivation process and enhanced AGS (E-AGS) cultivation process had significant differences (P < 0.005) in ARGs shift patterns. E-AGS process had higher average relative abundance (0.280 ± 0.079) of ARGs than T-AGS process (0.130 ± 0.041), while the intensity of ARGs enrichment during E-AGS (1.52-5.29 fold) was lower than T-AGS (3.79-75.31 fold) process. TnpA and intI1 as two different types of mobile genetic elements (MGEs) carrying ARGs, were observed to contribute significantly to the horizontal gene transfer (HGT) during T-AGS (r = 0.902, P < 0.050) and E-AGS (r = 0.823, P < 0.001) processes, respectively. Higher HGT level took place and more possible potential hosts (25 hosts) harboring ARGs were detected during E-AGS process comparing with T-AGS process (17 hosts). Meanwhile, over large AGS might increase the propagation of several antibiotic deactivation ARGs, so it was not advised. Overall, whether during T-AGS or during E-AGS process which was applied in a pilot-scale sequencing batch reactor treating municipal wastewater, the accumulation and spread of ARGs were inevitable. It should be valued that some suitable pre-treatments of seed sludge should be executed, meanwhile, advanced treatment for removing of ARGs in AGS should be conducted to maintain the relative abundances of ARGs at relatively low level.

11.
Circ Res ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32078445

RESUMO

Rationale: High-salt diet (HSD) is one of the most important risk factors for hypertension. Intestinal flora has been reported to be associated with high salt-induced hypertension (hSIH). However, the detailed roles of intestinal flora in hSIH pathogenesis have not yet been fully elucidated. Objective: To reveal the roles and mechanisms of intestinal flora in hSIH development. Methods and Results: The above-mentioned issues were investigated using various techniques including 16S rRNA gene sequencing, untargeted metabolomics, selective bacterial culture and fecal microbiota transplantation (FMT). We found that HSD induced hypertension in Wistar rats. The fecal microbiota of healthy rats could dramatically lower blood pressure (BP) of hypertensive rats, while the fecal microbiota of hSIH rats had opposite effects. The composition, metabolism and interrelationship of intestinal flora in hSIH rats were considerably reshaped, including the increased corticosterone level and reduced Bacteroides and arachidonic acid (AA) levels, which tightly correlated with BP. The serum corticosterone level was also significantly increased in rats with hSIH. Furthermore, the above abnormalities were confirmed in patients with hypertension. The intestinal Bacteroides fragilis (B. fragilis) could inhibit the production of intestinal-derived corticosterone induced by HSD through its metabolite AA. Conclusions: hSIH could be transferred by FMT, indicating the pivotal roles of intestinal flora in hSIH development. HSD reduced the levels of B. fragilis and AA in the intestine, which increased intestinal-derived corticosterone production and corticosterone levels in serum and intestine, thereby promoting BP elevation. This study revealed a novel mechanism different from inflammation/immunity by which intestinal flora regulated BP, namely intestinal flora could modulate BP by affecting steroid hormone levels. These findings enriched the understanding of the function of intestinal flora and its effects on hypertension.

12.
Ultrasound Med Biol ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32081585

RESUMO

To assess the feasibility of ultrasound imaging in depicting the changes in kidney size, hemodynamics and cortex viscoelasticity after hydration, we prospectively performed 2-D ultrasound shear wave elastography (SWE) and Doppler sonography of bilateral kidneys in 30 volunteers. Kidney length, cortex shear wave velocity (SWV), shear wave dispersion (SWD), interlobar artery peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistive index (RI) were measured before and 60 min after with and without drinking water (1 L). The differences in kidney length, SWV, PSV, EDV and color pixel intensity before and after hydration were significant (p < 0.001), whereas these differences were not significant without hydration (p > 0.05). SWD and RI did not significantly differ with or without hydration. Inter- and intra-observer reliability in performing SWE and Doppler sonography was good. The use of Doppler sonography and ultrasound SWE to evaluate the effect of hydration on kidney size, hemodynamics and viscoelasticity seem to be feasible.

13.
Gastric Cancer ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919745

RESUMO

PURPOSE: Here, we sought to develop a PET radioligand based on trastuzumab labeled with 124I, 124I-trastuzumab, to evaluate its distribution, internal dosimetry, and initial PET images of HER2-positive lesions in gastric cancer (GC) patients. METHODS: In animal studies, micro-PET imaging and bio-distribution were performed to examine the specificity of 124I-trastuzumab in HER2-positive and HER2-negative mouse models. Subsequently, 124I-trastuzumab was applied in human clinic trial. Six gastric cancer patients with metastases underwent 124I-trastuzumab PET imaging, with 18F-FDG PET/CT in each to compare. RESULTS: In animal studies, PET imaging of 124I-trastuzumab showed significant higher tumor uptake than that of 124I-IgG1 in HER2-positive PDX mouse models at 24 h. The low tumor uptake of 124I-trastuzumab in HER2-negative PDX models further confirmed the specificity. In human clinical studies, 18 HER2-positive lesions and 11 HER2-negative lesions were evaluated in PET imaging analysis. The detection sensitivity of 124I-trastuzumab was 100% (18/18) at 24 h. The PET images showed significant difference in tumor uptake between HER2-positive and HER2-negative lesions at 24 h (SUVmax 7.83 ± 0.55 vs. 1.75 ± 0.29, p < 0.0001). Quite striking difference in tumor uptake was observed between 124I-trastuzumab and 18F-FDG (SUVmax 1.75 ± 0.29 vs. 6.46 ± 0.44, p < 0.0001) in HER2-negative lesions, further confirming the specific binding of 124I-trastuzumab in HER2-positive lesions. The radiation-absorbed dose was calculated to be 0.3011 ± 0.005 mSv/MBq. No toxicities or adverse effects were observed in any of the patients. CONCLUSION: The findings described here demonstrated that 124I-trastuzumab was feasible to detect HER2-positive lesions in primary and metastatic gastric cancer patients and to differentiate HER2-positive and HER2-negative lesions quantitatively.

14.
Nanoscale ; 12(4): 2703-2714, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31950964

RESUMO

The Hippo signaling pathway plays critical roles in many biological processes including mechanotransduction. The key activator YAP of this pathway is considered as a central component of mechanotransduction signaling sensing the extracellular mechanical microenvironment changes, such as different cell density, the architecture of tissues and matrix stiffness. Although it has been largely studied that YAP is involved in these processes, the underlying mechanism of mechanical force-induced YAP regulation remains unclear. Here we exerted pressure on cell surfaces and investigated how YAP senses the extracellular mechanical force change using one of the super-resolution imaging techniques, dSTORM. We demonstrated that pressure promoted F-actin depolymerization, RhoA down-regulation, and LPAR1 (Gα12/13-coupled receptor) inactivation, which led to YAP cytoplasmic translocation and decreased clustering. Our work uncovers the role of GPCRs and F-actin in pressure-controlled YAP inactivation, and provides new insights into the mechanisms of mechanical regulation of the Hippo signaling pathway.

15.
Phys Chem Chem Phys ; 22(6): 3254-3263, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-31995071

RESUMO

On the basis of density functional theory (DFT) calculations, we have systematically investigated the structures and hydrogen evolution reaction (HER) catalytic activities for a series of new composite systems TM4@GDY (TM = Sc, Ti, Mn, Fe, Co, Ni and Cu), which are constructed by embedding tetrahedral 3d transition metal TM4 clusters in the in-plane cavity of two-dimensional (2D) π-conjugated graphdiyne (GDY). Our computed results reveal that compared with the constituent subunits, namely the sole TM4 cluster and GDY, all these composite TM4@GDY nanostructures can uniformly exhibit considerably high HER catalytic activity over a wide range of hydrogen coverage, and especially the Fe4@GDY and Co4@GDY systems can possess higher HER activity, in view of their higher number of active sites. The high HER catalytic activity for TM4@GDY can be mainly due to the occurrence of obvious electron transfer from TM4 cluster to GDY, significantly activating the correlative C and TM atoms. Moreover, all these composite TM4@GDY systems can also exhibit high structural stability and good conductivity. Therefore, all of them can be considered as a new kind of promising HER catalyst, and this study can provide new strategies for designing low-cost and high-performance 2D carbon-based electrocatalysts.

16.
J Cancer Res Clin Oncol ; 146(2): 329-342, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31912229

RESUMO

PURPOSE: Members of the aaRS (aminoacyl-tRNA synthetase) family are proteins controlling the aminoacylation process, in which YARS (tyrosyl-tRNA synthetase) catalyzes the binding of tyrosine to its cognate tRNA and plays an important role in basic biosynthesis. Several studies have demonstrated the association between YARS mutation and certain developmental abnormalities/diseases, yet YARS's linkage with cancer remains uncategorized. In this study, by combining in silico, in vitro, and in vivo studies, we explored the expressions and functions of YARS in gastric cancer (GC). METHODS: We evaluated YARS's distribution in tumor and paired normal tissues/specimens of GC by referring to large cohort online datasets and patient-derived tissue specimens. YARS-related changes were assessed by phenotypical/molecular experiments and RNA-sequencing analysis in GC cell lines harboring YARS knockdown or overexpression. RESULTS: Both the transcript and protein levels of YARS were evidently higher in gastric cancer tissues than in paired normal tissues. YARS knockdown induced repressed proliferation and invasiveness, as well as enhanced apoptosis in GC cell lines, while abnormally upregulating YARS expression promoted gastric cancer growth in vivo. We inferred based on RNA-sequencing that YARS modulates multiple cancerous signaling pathways and proved through cellular experiments that YARS promoted GC progression, as well as homologous recombination by activating PI3K-Akt signaling. CONCLUSIONS: By revealing the existence of a YARS-PI3K-Akt signaling axis in gastric cancer, we discovered that tRNA synthetase YARS is a novel tumorigenic factor, characterized by its upregulation in tumor-derived specimens, as well as its functions in promoting gastric cancer progression.

17.
Int Immunopharmacol ; 80: 106219, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31991373

RESUMO

Fibroblast Growth Factor 21 (FGF21) has been reported to reduce inflammation and apoptosis. Inflammation and apoptosis are both the essential mechanisms during development of acute lung injury. This study evaluated whether pre-treatment of FGF21 could alleviate acute lung injury. Mice were pre-treated with FGF21 prior to lipopolysaccharide (LPS) treatment. 24 h later, the lung tissues and BALF were obtained to detect H&E pathology, W/D ratio, pro-inflammatory factors (TNF-α, IL-1ß and IL-6) and apoptosis. In vitro, Human BEAS-2B and THP-1 cells were overexpressed with TLR4 or MYD88 or NF-κB plasmid to detect the inflammation or apoptosis. Data showed that FGF21 was proved to be beneficial for inhibiting inflammation and apoptosis in the LPS- induced Balb/c mice or LPS induced BEAS-2B or THP-1 cells. Furthermore, the data showed that FGF21 suppressed inflammation and apoptosis via inhibition of TLR4/MYD88/NF-κB signaling pathway. Therefore, FGF21 provides a possibility for the treatment of LPS induced acute lung injury.

18.
ACS Appl Mater Interfaces ; 12(5): 5680-5694, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31944660

RESUMO

Photodynamic therapy (PDT), a clinically approved cancer treatment, has faced many drawbacks that restricted its applications. For example, the hypoxia-induced elevated hypoxia-inducible factor-1α (HIF-1α) may desensitize tumors to PDT, and the high concentration of glutathione (GSH) in cancer cells can also neutralize the generated reactive oxygen species (ROS) during PDT, resulting in insufficient therapy. Moreover, extra probes for imaging-guided visualization therapy are always needed to track drug release or distribution, while it may decrease the drug loading of the drug delivery system (DDS). In the present study, we have designed and prepared a novel multifunctional combined therapy nanoparticle (ZnPc@Cur-S-OA NPs), in which curcumin (Cur) was not only used as a chemotherapy drug to achieve a combination therapy with PDT via downregulating HIF-1α and depleting GSH in B16F10 cells but also designed as a small-molecule ROS-triggered release prodrug to deliver the photosensitizer (PS). The red fluorescence of PS in the nanoparticles (NPs) can be used to track the NPs distribution, while the green fluorescence of Cur showed an "OFF-ON" activation, which enables additional imaging and real-time self-monitoring capabilities. These results proved that the prepared combined therapy NPs were more effective to inhibit the growth of B16F10 mouse melanoma tumor than was monotherapy without eliciting systemic toxicity either in vitro or in vivo, which indicated the combined therapy NPs as an effective way to improve the PDT efficacy via downregulation of HIF-1α and depletion of GSH. Thus, the strategy of using a multifunctional natural product as the stimuli-responsive carrier as well as the synergist with PDT for enhancing antitumor efficacy via multiple pathways may open an alternative avenue to fabricate new self-delivery combination therapy nanodrugs. Besides, the fluorescence emitted from the drug can be used for real-time self-monitoring of drug release and distribution, which has great potential in clinic to adjust the administration dose and irradiation time for different tumor types and stages for individual therapy.

19.
J Proteome Res ; 19(2): 962-972, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31922419

RESUMO

Aspirin, or acetylsalicylic acid (ASA), is the most widely used medication to relieve pain, fever, and inflammation. Recent studies have revealed new benefits of aspirin, including reduction of heart attack and stroke, anticancer, and life extension. Despite the profound effects of aspirin, the mechanism of its action remains to be elucidated. Here, we used deuterium-labeled aspirin (D-aspirin) together with mass spectrometry-based acetylomic analysis, termed DAcMS, to investigate the landscape of protein acetylation induced by aspirin. The DAcMS revealed the acetylomes of lipopolysaccharide-induced inflammatory BV2 cells and colon cancer HCT116 cells. The acetylation level was substantially induced upon aspirin treatment in both cell lines. In total, we identified 17,003 acetylation sites on 4623 proteins in BV2 cells and 16,366 acetylated sites corresponding to 4702 acetylated proteins in HCT116 cells. Importantly, functional analyses of these aspirin-induced acetylated proteins suggested that they were highly enriched in many key biological categories, which function importantly in inflammatory response. We further demonstrated that aspirin acetylates proteins through both acetyl-CoA-dependent and acetyl-CoA-independent pathways, and the accessible lysine residues at the protein surface are major acetylation targets of aspirin. Hence, our study provides the comprehensive atlas of aspirin-induced acetylome under disease conditions. This knowledge proffers new insight into the aspirin-directed acetylome and perhaps new drug target sites relevant to human cancer and inflammatory diseases. The MS data of this study have been deposited under the accession number IPX0001923000 at iProX.

20.
Int J Neural Syst ; 30(2): 2050001, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31969078

RESUMO

Neuromodulation plays a vital role in the prevention and treatment of neurological and psychiatric disorders. Neuromodulation's feasibility is a long-standing issue because it provides the necessity for neuromodulation to realize the desired purpose. A controllability analysis of neural dynamics is necessary to ensure neuromodulation's feasibility. Here, we present such a theoretical method by using the concept of controllability from the control theory that neuromodulation's feasibility can be studied smoothly. Firstly, networks of multiple coupled neural populations with different topologies are established to mathematically model complicated neural dynamics. Secondly, an analytical method composed of a linearization method, the Kalman controllable rank condition and a controllability index is applied to analyze the controllability of the established network models. Finally, the relationship between network dynamics or topological characteristic parameters and controllability is studied by using the analytical method. The proposed method provides a new idea for the study of neuromodulation's feasibility, and the results are expected to guide us to better modulate neurodynamics by optimizing network dynamics and network topology.

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