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1.
Eur J Pediatr ; 2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-32488736

RESUMO

The authors regrets that there is a typo error on the Abbreviation section of their published paper. "Area under the curve" should have been abbreviated to "AUC" instead of "A". The authors have requested that this be noted. The original article has been corrected.

2.
Small ; 16(23): e2001059, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32378337

RESUMO

Hypoxia severely impedes photodynamic therapy (PDT) efficiency. Worse still, considerable tumor metastasis will occur after PDT. Herein, an organic superoxide radical (O2 ∙- ) nano-photogenerator as a highly effcient type I photosensitizer with robust vascular-disrupting efficiency to combat these thorny issues is designed. Boron difluoride dipyrromethene (BODIPY)-vadimezan conjugate (BDPVDA) is synthesized and enwrapped in electron-rich polymer-brushes methoxy-poly(ethylene glycol)-b-poly(2-(diisopropylamino) ethyl methacrylate) (mPEG- PPDA) to afford nanosized hydrophilic type I photosensitizer (PBV NPs). Owing to outstanding core-shell intermolecular electron transfer between BDPVDA and mPEG-PPDA, remarkable O2 ∙- can be produced by PBV NPs under near-infrared irradiation even in severe hypoxic environment (2% O2 ), thus to accomplish effective hypoxic-tumor elimination. Simultaneously, the efficient ester-bond hydrolysis of BDPVDA in the acidic tumor microenvironment allows vadimezan release from PBV NPs to disrupt vasculature, facilitating the shut-down of metastatic pathways. As a result, PBV NPs will not only be powerful in resolving the paradox between traditional type II PDT and hypoxia, but also successfully prevent tumor metastasis after type I PDT treatment (no secondary-tumors found in 70 days and 100% survival rate), enabling enhancement of existing hypoxic-and-metastatic tumor treatment.

3.
Eur J Pediatr ; 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32394266

RESUMO

The aim of this study is to explore the prognostic values and optimal cutoff point of time to positivity (TTP) of blood culture in children with Klebsiella pneumoniae (K. pneumoniae) bloodstream infection. Ninety-four children with K. pneumoniae bloodstream infection hospitalized in Children's Hospital of Chongqing Medical University from April 2014 to January 2019 were enrolled retrospectively. TTP and risk factors were determined and analyzed by receiver operating characteristic (ROC) analysis and logistic regression analysis. The standard cutoff point of TTP was 13 h. Patients in early TTP (≤ 13 h) group had significantly higher in-hospital mortality (37.93% vs 6.15%, P = 0.000), higher incidence of septic shock (44.83% vs 6.15%, P = 0.000), higher proportion of PRISM III scores ≥ 10 (48.28% vs 20.00%, P = 0.005), and higher proportion of hypoalbuminemia on admission (44.83% vs 18.46%, P = 0.008). Multivariate analysis indicated PRISM III scores ≥ 10, early TTP, and hypoalbuminemia on admission were independent risk factors of in-hospital mortality (OR 8.36, 95% CI 1.80-38.92, P = 0.007; OR 5.85, 95% CI 1.33-25.61, P = 0.019; OR 5.73, 95% CI 1.30-25.22, P = 0.021, respectively) and septic shock (OR 14.04, 95% CI 2.63-75.38, P = 0.002; OR 11.26, 95% CI 2.10-60.22, P = 0.005; OR 10.27, 95% CI 2.01-52.35, P = 0.005, respectively).Conclusion: Early TTP (TTP ≤ 13 h), PRISM III scores ≥ 10, and hypoalbuminemia on admission appeared to be associated with worse outcomes for K. pneumoniae bloodstream infection children.What is Known:• Klebsiella pneumoniae bloodstream infection is an important cause of infectious disease morbidity and mortality worldwide in children.• Short duration of time to positivity indicated poor clinical outcomes.What is New:• Time to positivity ≤ 13 h, along with PRISM III scores ≥ 10 and hypoalbuminemia on admission, indicated higher in-hospital mortality and incidence of septic shock in Klebsiella pneumoniae bloodstream infection children.• The cut-off point of TTP in this pediatric study was much longer than that reported in adult patients.

4.
Chin Med J (Engl) ; 133(12): 1436-1444, 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32472783

RESUMO

BACKGROUND: Degree of mucosal recovery is an important indicator for evaluating the therapeutic effects of drugs in treatment of inflammatory bowel disease (IBD). Increasing evidences has proved that tight junction (TJ) barrier dysfunction is one of the pathological mechanisms of IBD. The aim of this study was to observe whether enhancement of TJ can decrease colitis recurrence. METHODS: Eighty C57BL/6 mice were randomly divided into four groups including normal group, colitis group, sulfasalazine (SASP) treated group, and traditional Chinese drug salvianolic acid B (Sal B) treated group. Colitis was established in mice by free drinking water containing dextran sulfate sodium, after treatments by SASP and Sal B, recombinant human interleukin-1ß (IL-1ß) was injected intraperitoneally to induce colitis recurrence. RESULTS: Compared with sham control, cell apoptosis in colitis group was increased from 100.85 ±â€Š3.46% to 162.89 ±â€Š11.45% (P = 0.0038), and TJ dysfunction marker myosin light chain kinase (MLCK) was also significantly increased from 99.70 ±â€Š9.29% to 296.23 ±â€Š30.78% (P = 0.0025). The increased cell apoptosis was reversed by both SASP (125.99 ±â€Š8.45% vs. 162.89 ±â€Š11.45%, P = 0.0059) and Sal B (104.27 ±â€Š6.09% vs. 162.89 ±â€Š11.45%, P = 0.0044). High MLCK expression in colitis group was reversed by Sal B (182.44 ±â€Š89.42% vs. 296.23 ±â€Š30.78%, P = 0.0028) but not influenced by SASP (285.23 ±â€Š41.04% vs. 296.23 ±â€Š30.78%, P > 0.05). The recurrence rate induced by recombinant human IL-1ß in Sal B-treated group was significantly lower than that in SASP-treated group. CONCLUSIONS: These results suggested a link between intestinal mucosal barrier dysfunction, especially TJ barrier dysfunction, and colitis recurrence. The TJ barrier dysfunction in remission stage of colitis increased the colitis recurrence. This study might provide potential treatment strategies for IBD recurrence.

5.
ACS Appl Mater Interfaces ; 12(24): 26914-26925, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32463220

RESUMO

Cancer phototheranostics, composed of optical diagnosis and phototherapy (including photodynamic therapy and photothermal therapy), is a promising strategy for precise tumor treatment. Due to the unique properties of near-infrared absorption/emission, high reactive oxygen species generation, and photothermal conversion efficiency, aza-boron-dipyrromethene (aza-BODIPY), as an emerging organic photosensitizer, has shown great potential for tumor phototheranostics. By encapsulating aza-BODIPY photosensitizers within functional amphiphilic polymers, we can afford hydrophilic nanomedicines that selectively target tumor sites via an enhanced permeability and retention effect, thereby efficiently improving diagnosis and therapeutic efficacy. Herein, in this spotlight article, we attempt to highlight our recent contributions in the development of aza-BODIPY-based nanomedicines, which comprises three main sections: (1) to elucidate the design strategy of aza-BODIPY photosensitizers and corresponding nanomedicines; (2) to overview their photophysical properties and biomedical applications in phototheranostics, including fluorescence imaging, photoacoustic imaging, photodynamic therapy, photothermal therapy, and synergistic therapy; and (3) to depict the challenges and future perspectives of aza-BODIPY nanomedicines. It is believed that this Spotlight on Applications article would illuminate the way of developing new aza-BODIPY nanomedicines as well as other organic photosensitizer-based nanomedicines for future clinical translation.

6.
Cell Death Dis ; 11(5): 404, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32472021

RESUMO

Dysfunction of intestinal epithelial Cl- currents and channels have previously been reported in inflammatory intestinal diseases. However, the expression and function of the newly identified Ca2+-activated Cl- channel transmembrane member 16A (TMEM16A) in the intestinal epithelium is unclear. In this study, we investigated the effects of TMEM16A on intestinal epithelial barrier function in vitro. Intestinal epithelial barrier dysfunction was modeled by lipopolysaccharide (LPS)-induced cell damage in intestinal epithelial IEC-6 cells and the effects of TMEM16A knockdown and overexpression on cell apoptosis and tight junctions were studied. Corresponding mRNA and protein expression levels were measured by quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence analysis, respectively. TMEM16A expression was significantly increased by LPS, possibly via a process involving the transcription factor nuclear factor-κB and both Th1 and Th2 cytokines. Low- and high-dose LPS dysregulated tight junctions (high-myosin light-chain kinase expression) and cell apoptosis-dependent cell barrier dysfunction, respectively. TMEM16A aggravated cell barrier dysfunction in IEC-6 cells pretreated with low-dose LPS by activating ERK1/MLCK signaling pathways, but protected against cell barrier dysfunction by activating ERK/Bcl-2/Bax signaling pathways in IEC-6 cells pretreated with high-dose LPS. We concluded that TMEM16A played a dual role in LPS-induced epithelial dysfunction in vitro. The present results indicated the complex regulatory mechanisms and targeting of TMEM16A may provide potential treatment strategies for intestinal epithelial barrier damage, as well as forming the basis for future studies of the expression and function of TMEM16A in normal and inflammatory intestinal diseases in vivo.

7.
Sci Rep ; 10(1): 7647, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32376992

RESUMO

Tuberculosis remains a global health threat killing over 1 million people per year. Current sputum-based diagnostics are specific but lack sensitivity resulting in treatment of many sputum negative cases. In this proof-of-concept study, we used high-resolution mass spectrometry to identify specific lipids in peripheral lung fluid samples of TB patients and controls, captured using a novel non-invasive sampling system. Exhaled respiratory particles were collected in liquid and after concentration and lipid extraction directly infused into a high-resolution mass spectrometer. High-resolution mass spectrometric data collection was conducted in a dual ion mode and chemical compositions were constructed using accurate mass measurement. Over 400 features with high segregating capacity were extracted and optimized using feature selection algorithm and machine learning, from which the accuracy of detection of positive tuberculosis patients was estimated. This current strategy provides sensitivity offered by high-resolution mass spectrometry and can be readily susceptible for developing a novel clinical assay exploring peripheral lung fluid for the detection of active TB cases.

8.
Acta Pharmacol Sin ; 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32238887

RESUMO

Our preliminary study shows that cinnamaldehyde (CA) could protect against intestinal ischemia/reperfusion (I/R) injuries, in which p53 and NF-κB p65 play a synergistic role. In this study, we conducted in vivo and in vitro experiments to verify this proposal. SD rats were pretreated with CA (10 or 40 mg · kg-1 · d-1, ig) for 3 days, then subjected to 1 h mesenteric ischemia followed by 2 h reperfusion. CA pretreatment dose-dependently ameliorated morphological damage and reduced inflammation evidenced by decreased TNF-α, IL-1ß, and IL-6 levels and MPO activity in I/R-treated intestinal tissues. CA pretreatment also attenuated oxidative stress through restoring SOD, GSH, LDH, and MDA levels in I/R-treated intestinal tissues. Furthermore, CA pretreatment significantly reduced the expression of inflammation/apoptosis-related NF-κB p65, IKKß, IK-α, and NF-κB p50, and downregulated apoptotic protein expression including p53, Bax, caspase-9 and caspase-3, and restoring Bcl-2, in I/R-treated intestinal tissues. We pretreated IEC-6 cells in vitro with CA for 24 h, followed by 4 h hypoxia and 3 h reoxygenation (H/R) incubation. Pretreatment with CA (3.125, 6.25, and 12.5 µmol · L-1) significantly reversed H/R-induced reduction of IEC-6 cell viability. CA pretreatment significantly suppressed oxidative stress, NF-κB activation and apoptosis in H/R-treated IEC-6 cells. Moreover, CA pretreatment significantly reversed mitochondrial dysfunction in H/R-treated IEC-6 cells. CA pretreatment inhibited the nuclear translocation of p53 and NF-κB p65 in H/R-treated IEC-6 cells. Double knockdown or overexpression of p53 and NF-κB p65 caused a synergistic reduction or elevation of p53 compared with knockdown or overexpression of p53 or NF-κB p65 alone. In H/R-treated IEC-6 cells with double knockdown or overexpression of NF-κB p65 and p53, CA pretreatment caused neither further decrease nor increase of NF-κB p65 or p53 expression, suggesting that CA-induced synergistic inhibition on both NF-κB and p53 played a key role in ameliorating intestinal I/R injuries. Finally, we used immunoprecipitation assay to demonstrate an interaction between p53 and NF-κB p65, showing the basis for CA-induced synergistic inhibition. Our results provide valuable information for further studies.

9.
J Mater Chem B ; 8(15): 2990-3004, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32211649

RESUMO

Anti-vascular agents (AVAs) are a class of promising therapeutic agents with tumor vasculature targeting properties, which can be divided into two types: anti-angiogenic agents (AAAs, inhibit angiogenesis factors) and vascular disrupting agents (VDAs, disrupt established tumor vasculature). AVAs exhibit an enhanced anti-cancer effect by cutting off the oxygen and nutrition supplement channels of tumors. However, the intrinsic drawbacks, such as poor hydrophilicity, undesirable membrane permeability and inferior tumor targeting ability, discount their anti-vascular efficacy. Fortunately, the development of nanotechnology has brought an opportunity for efficient delivery of AVAs to tumour sites with great therapeutic efficacy. The works summarized in this review will provide an understanding of recent advances of anti-vascular nano agents (AVNAs) with a goal to define the mechanism of anti-vascular-based cancer therapy and discuss the challenges and opportunities of AVNAs for clinical translation.

10.
Int Immunopharmacol ; 82: 106356, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32151958

RESUMO

Interferon-γ (IFN-γ) is traditionally regarded as a proinflammatory cytokine by virtue of its strong macrophage activating potential and its association with Th1 driven immune responses. NOD1 and NOD2 are cytoplasmic receptors that can initiate the initial immune response by sensing bacterial components or danger signals. In this study, we investigated the immunopathological roles of IFN-γ and NOD1, 2 ligands iE-DAP/MDP on the activation of fibroblast-like synoviocytes (FLS) in RA. FLS constitutively express functional NOD1 and NOD2, and the gene and protein expression of NOD1 and NOD2 could be enhanced by the treatment with IFN-γ. The synergistic effect was observed in the combined treatment of IFN-γ and NOD1 ligand iE-DAP or NOD2 ligand MDP on the release of CCL5, CXCL9 and CXCL10 from FLS, and its effect was in a dose-dependent manner. The co-stimulation which IFN-γ combined with iE-DAP/MDP could abolish the inhibition of CXCL8 level by IFN-γ alone. Further investigations showed that synergistic effects on the production of CCL5, CXCL9 and CXCL10 in FLS stimulated by IFN-γ and iE-DAP/MDP were differentially regulated by intracellular activation of NF-κB, p38MAPK and ERK pathways. In conclusion, our data confirmed the inflammatory effect of IFN-γ and iE-DAP/MDP on human FLS for the first time and therefore provided a new insight into the IFN-γ combined with NOD1 or NOD2 activated immunopathological mechanisms mediated by distinct intracellular signal transduction in joint inflammation of RA.

11.
Int J Mol Med ; 45(3): 939-946, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31985021

RESUMO

Acute kidney injury (AKI) is characterized by abrupt kidney dysfunction. It results in remote organ dysfunction, including the brain. The underlying mechanism of the kidney­brain axis in AKI and effective protective approaches remain unknown. The present study aimed to investigate the potential protective effect of ginsenoside (GS) on AKI induced by glycerol in rats. Kidney function was initially assessed by blood urea nitrogen (BUN) and creatinine (Cre) tests, and was identified to be severely impaired following glycerol treatment, based on significant increases in BUN and Cre levels observed. Severe extensive necrosis of the majority of the renal tubules was observed by hematoxylin and eosin staining, additionally confirming that glycerol induced AKI. GS was identified to ameliorate the impairment of kidney function in the context of AKI. Further investigation of the mechanism revealed that GS may induce protection against oxidative stress via a kidney­brain axis. Furthermore, GS improved the activation of hypoxia­inducible factor 1α (HIF­1α) and vascular endothelial growth factor A (VEGF­A) in the hypothalamus response to AKI, and in the kidney tissues. The protective effect of GS in AKI may be associated with the interaction between the kidney and the brain. Taken together, these results suggested that GS was involved in the protective effects against AKI by decreasing oxidative damage to the kidney and brain, and by upregulating HIF­1α and VEGF­A levels in the kidney­brain axis.

12.
Cytokine ; 128: 155000, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31982701

RESUMO

BACKGROUND: Infections are leading causes of morbidity and mortality in neonates and may also have severe long-term consequences. As early diagnosis of neonatal sepsis improves prognosis, identification of new or complementary biomarkers is of great importance. In this study, we have evaluated the diagnostic value of progranulin (PGRN) in early-onset neonatal sepsis (EOS) and compare its effectiveness with other commonly used biomarkers, such as procalcitonin (PCT) and C-reactive protein (CRP). METHODS: A total of 121 infants with gestational age of >34 weeks admitted with suspected EOS were included in this study. Before initiating therapy, blood samples for whole blood count, CRP, PCT and PGRN were obtained from all neonates. Receiver-operating characteristic (ROC) curve and multivariate logistic regression analyses were performed. RESULTS: Serum PGRN level of infected group was significantly higher than uninfected group (median 47.72 vs. 37.86 ng/ml, respectively; Mann-Whitney p < 0.0001). The ROC area under the curve (AUC) was 0.786 [95% confidence interval (CI) 0.706-0.867; p < 0.0001] for PGRN, 0.699 (95% CI 0.601-0.797; p = 0.0001) for age adjusted PCT, and 0.673 (95% CI 0.573-0.773; p = 0.0007) for CRP. With a cut-off value of 37.89 ng/ml, the diagnostic sensitivity and negative predictive value of PGRN were 94.34% and 91.7%, respectively. PGRN could significantly predict EOS independently of PCT (p < 0.0001), and the combined use of PGRN and PCT could significantly improve diagnostic performance for EOS (0.806; 95% CI 0.73-0.88; p < 0.0001), with a specificity of 89.06% and a positive predictive value of 81.10%. CONCLUSIONS: PGRN may be used as a promising biomarker for the diagnosis of EOS, and the combined use of PGRN and PCT could improve the diagnosis of sepsis.

13.
Am J Respir Cell Mol Biol ; 62(6): 760-766, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31991091

RESUMO

Invasive pulmonary aspergillosis is a life-threatening disease, particularly in immunocompromised patients, despite currently available therapy. IL-27 is an important regulatory cytokine in infection and immunity. However, its role in the pathogenesis of invasive pulmonary aspergillosis remains unknown. Here we found that Aspergillus fumigatus pulmonary infection induced an elevated production of IL-27 in the lung. As compared with wild-type (WT) mice, IL-27R (IL-27 receptor)-deficient mice developed less severe infection when challenged with A. fumigatus conidia, as evidenced by the decreased fungal colonization and pathology of lungs and the increased survival. IL-27R deficiency led to significantly higher production of IFN-γ in the lung after A. fumigatus infection, and the increased resistance to invasive pulmonary A. fumigatus infection in IL-27R-deficient mice was ablated by neutralizing IFN-γ. Importantly, neutralization of IL-27 could protect WT mice against invasive pulmonary A. fumigatus infection. Our data therefore suggest an important role of IL-27 in impairing anti-A. fumigatus host immunity, which may have translational implications in treating clinical cases of invasive pulmonary aspergillosis.

14.
Bioorg Med Chem Lett ; 30(1): 126715, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31757666

RESUMO

A high-throughput screening (HTS) campaign identified a class of heteroaryl piperazines with excellent baseline affinity and selectivity for phosphoinositide 3-kinase δ (PI3Kδ) over closely related isoforms. Rapid evaluation and optimization of structure-activity relationships (SAR) for this class, leveraging the modular nature of this scaffold, facilitated development of this hit class into a series of potent and selective inhibitors of PI3Kδ. This effort culminated in the identification of 29, which displayed excellent potency in enzyme and cell-based assays, as well as favorable pharmacokinetic and off-target profiles.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31751224

RESUMO

Person re-identification (re-ID) aims to robustly measure visual affinities between person images. It has wide applications in intelligent surveillance by associating same persons' images across multiple cameras. It is generally treated as an image retrieval problem: given a probe person image, the affinities between the probe image and gallery images (P2G affinities) are used to rank the retrieved gallery images. There exist two main challenges for effectively solving this problem. 1) Person images usually show significant variations because of different person poses and viewing angles. The spatial layouts and correspondences between person images are therefore vital information for tackling this problem. State-of-the-art methods either ignore such spatial variation or utilize extra pose information for handling the challenge. 2) Most existing person re-ID methods rank gallery images considering only P2G affinities but ignore the affinities between the gallery images (G2G affinity). Such affinities could provide important clues for accurate gallery image ranking but were only utilized in post-processing stages by current methods. In this paper, we propose a unified end-to-end deep learning framework to tackle the two challenges. For handling viewpoint and pose variations between compared person images, we propose a novel Kronecker Product Matching operation to match and warp feature maps of different persons. Comparing warped feature maps results in more accurate P2G affinities. To fully utilize all available P2G and G2G affinities for accurately ranking gallery person images, a novel group-shuffling random walk operation is proposed. Both Kronecker Product Matching and Group-shuffling Random Walk operations are end-to-end trainable and are shown to improve the learned visual features if integrated in the deep learning framework. The proposed approach outperforms state-of-the-art methods on Market-1501, CUHK03 and DukeMTMC datasets, which demonstrates the effectiveness and generalization ability of our proposed approach. Code is available at https://github.com/YantaoShen/kpm rw person reid.

16.
J Proteome Res ; 18(11): 4013-4019, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31545043

RESUMO

A top-down proteomic strategy with semiautomated analysis of data sets has proven successful for the global identification of truncated proteins without the use of chemical derivatization, enzymatic manipulation, immunoprecipitation, or other enrichment. This approach provides the reliable identification of internal polypeptides formed from precursor gene products by proteolytic cleavage of both the N- and C-termini, as well as truncated proteoforms that retain one or the other termini. The strategy has been evaluated by application to the immunosuppressive extracellular vesicles released by myeloid-derived suppressor cells. More than 1000 truncated proteoforms have been identified, from which binding motifs are derived to allow characterization of the putative proteases responsible for truncation.

17.
Pharmacol Res ; 148: 104461, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31542404

RESUMO

Intestinal epithelial barrier dysfunction is a key pathology of colitis. Autophagy of epithelial cells maintains homeostasis of the intestinal barrier by inhibiting apoptosis and stimulating degradation of the tight junction protein claudin-2. This study investigated the effects and mechanism of activity of sinensetin, a polymethylated flavonoid isolated from tangerine peel and citrus, on intestinal barrier dysfunction in colitis. Animal model of colitis were established by intracolonic administration of 2, 4, 6-trinitrobenzene sulfonic acid and oral treatment with dextran sulfate sodium. Epithelial barrier function was evaluated by measuring the serum recovery of fluorescein isothiocyanate-4 kD dextran in vivo and transepithelial electrical resistance in Caco-2 cells, respectively. Epithelial cell autophagy assayed by autophagosome formation and expression of autophagy-related protein. Sinensetin reversed colitis-associated increase in intestinal permeability, significantly promoted epithelial cell autophagy, and further decreased epithelial cell apoptosis, and reduced mucosal claudin-2. Sinenstetin alleviated colitis symptoms rats and mice with colitis. Knockdown of 5' adenosine monophosphate-activated protein kinase (AMPK) reversed the promotion of epithelial autophagy by sinensetin. In conclusion, sinensetin significantly alleviated intestinal barrier dysfunction in colitis by promoting epithelial cell autophagy, and further inhibiting apoptosis and promoting claudin-2 degradation. The results highlighted novel potential benefits of sinensetin in colitis.

18.
Biosci Rep ; 39(10)2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31551340

RESUMO

AIM: IgA nephropathy (IgAN) is one of the most common chronic glomerulonephritis. Its etiology and pathogenesis remain unclear. We thus explored the immune repertoire of the B-cell receptor (BCR) and the heavy-chain complementarity-determining region 3 (CDR3) in renal tissue and peripheral blood of IgAN patients. METHOD: Total RNAs extracted from renal tissues and peripheral blood of patients and peripheral blood of healthy controls (HCs) were analyzed via high-throughput multiplex PCR sequencing. We amplified and sequenced BCR heavy-chain CDR3 regions to explore repertoire diversity, V/J gene family distribution, CDR3 lengths, BCR heavy-chain variants, consistency between tissue and peripheral blood data, and clones 'shared' by these bodily compartments. RESULTS: We identified the renal tissue and peripheral blood BCR heavy-chain CDR3 immune repertoires of 15 IgAN patients. Top1 could be more readily cloned from peripheral blood of patients than from controls (P<0.05), the average CDR3 length was significantly shorter in patients than in HCs (P<0.05), the variant frequency of the gene encoding the BCR heavy chain was higher in patients than in HCs (P<0.05), and the BCR variant frequency was highest in IgAN kidney tissue. Preliminary screening for 'shared' clones showed that, in at least 13 patients, the 'ALYFHNSAY', 'ARWGPMYYYMDV', 'ARDQGALNA', and 'ARVDNPADF' CDR3 sequences were evident in peripheral blood samples from patients, but not HCs. CONCLUSIONS: We found that the 'ALYFHNSAY', 'ARWGPMYYYMDV', 'ARDQGALNA', and 'ARVDNPADF' clonal sequences may be useful for noninvasive diagnosis and treatment planning in IgAN.

19.
Micromachines (Basel) ; 10(10)2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547592

RESUMO

Wafer bonding of a silicon carbide (SiC) diaphragm to a patterned SiC substrate coated with aluminum nitride (AlN) film as an insulating layer is a promising choice to fabricate an all-SiC capacitive pressure sensor. To demonstrate the bonding feasibility, a crystalline AlN film with a root-mean-square (RMS) surface roughness less than ~0.70 nm was deposited on a SiC wafer by a pulsed direct current magnetron sputtering method. Room temperature wafer bonding of SiC-AlN by two surface activated bonding (SAB) methods (standard SAB and modified SAB with Si nano-layer sputtering deposition) was studied. Standard SAB failed in the bonding, while the modified SAB achieved the bonding with a bonding energy of ~1.6 J/m2. Both the microstructure and composition of the interface were investigated to understand the bonding mechanisms. Additionally, the surface analyses were employed to confirm the interface investigation. Clear oxidation of the AlN film was found, which is assumed to be the failure reason of direct bonding by standard SAB.

20.
Biomaterials ; 221: 119422, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31437723

RESUMO

Highly specific and effective cancer phototherapy remains as a great challenge. Herein, a smart nanoplatform (TENAB NP) sequentially responsive to light, low pH and hypoxia is demonstrated for multi-mode imaging guided synergistic cancer therapy with negligible skin phototoxicity. Upon 808-nm laser irradiation, TENAB NPs can generate hyperthermia to melt the phase change material (PCM-LASA) coat and thereafter release chemo-drug tirapazamine (TPZ). Meanwhile, under acidic pH, photosensitizer ENAB would turn "off" its charge-transfer state, generating prominent 1O2 for photodynamic therapy (PDT) and heat for photothermal therapy (PTT), respectively. Accompanied with PDT-induced hypoxia, the released TPZ can be activated into its cytotoxic form for tumor cells killing. Notably, owing to phase change material LASA coat and ENAB's pH sensitivity, TENAB NPs show negligible photosensitization to skin and normal tissues. As the multi-stimuli responsive mechanism, TENAB NPs demonstrate a promising future in cancer photo-chemo theranostics with excellent skin protection.

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