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1.
Mol Carcinog ; 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32424979

RESUMO

Drug resistance is the leading cause for rapid progression and relapse in small-cell lung cancer (SCLC) patients. Thus overcoming drug resistance still remains to be urgently resolved during SCLC treatment. Here, we found p62/SQSTM1 was enriched in SCLC spheroids, a subpopulation possessing cancer stem-like properties, which is responsible for cancer relapse and metastasis. Subsequent functional assays in vitro showed that short hairpin RNA (shRNA)-mediated p62 knockdown increased sensitivity of SCLC cell lines to cisplatin (DDP), whereas lentivirus-mediated p62 ectopic overexpression diminished DDP-induced cytotoxicity in both NCI-H446 and NCI-H1688 cell lines. Moreover, ectopic p62 overexpression promoted DDP resistance of NCI-H446 cells-derived tumor xenografts in immunodeficient mice in vivo, as indicated by accelerated tumor growth rate and reduced fluorescent activity of cleaved caspase-3. Gene expression profiling analysis revealed that p62 was positively correlated with neuronal precursor cell-expressed, developmentally downregulated gene 9 (NEDD9) expression level. Consistently, NEDD9 messenger RNA (mRNA) level was decreased upon p62 suppression by small interfering RNA (siRNA) and increased with p62 transient overexpression in SCLC cell lines, suggesting that p62 positively regulated NEDD9 mRNA. Depletion of NEDD9 by siRNA, to a large extent, reversed p62-overexpressed SCLC cells to DDP-induced cytotoxicity, implying NEDD9 might act as a downstream target which was in charge of p62-mediated DDP resistance. Taken together, our findings uncovered a previously unknown role of p62 in the regulation of SCLC drug resistance, assigning p62 as an attractive target for SCLC treatment.

2.
Nat Methods ; 17(5): 531-540, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32371980

RESUMO

Single-molecule localization microscopy is a powerful tool for visualizing subcellular structures, interactions and protein functions in biological research. However, inhomogeneous refractive indices inside cells and tissues distort the fluorescent signal emitted from single-molecule probes, which rapidly degrades resolution with increasing depth. We propose a method that enables the construction of an in situ 3D response of single emitters directly from single-molecule blinking datasets, and therefore allows their locations to be pinpointed with precision that achieves the Cramér-Rao lower bound and uncompromised fidelity. We demonstrate this method, named in situ PSF retrieval (INSPR), across a range of cellular and tissue architectures, from mitochondrial networks and nuclear pores in mammalian cells to amyloid-ß plaques and dendrites in brain tissues and elastic fibers in developing cartilage of mice. This advancement expands the routine applicability of super-resolution microscopy from selected cellular targets near coverslips to intra- and extracellular targets deep inside tissues.

3.
Aging (Albany NY) ; 122020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32434960

RESUMO

Bone volume inadequacy is an emerging clinical problem impairing the feasibility and longevity of dental implants. Human bone marrow mesenchymal stem cells (HBMSCs) have been widely used in bone remodeling and regeneration. This study examined the effect of long noncoding RNAs (lncRNAs)-H19 on the human amnion-derived mesenchymal stem cells (HAMSCs)-droved osteogenesis in HBMSCs. HAMSCs and HBMSCs were isolated from abandoned amniotic membrane samples and bone marrow. The coculture system was conducted using transwells, and H19 level was measured by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). The mechanism was further verified. We here discovered that osteogenesis of HBMSCs was induced by HAMSCs, while H19 level in HAMSCs was increased during coculturing. H19 had no significant effect on the proliferative behaviors of HBMSCs, while its overexpression of H19 in HAMSCs led to the upregulated osteogenesis of HBMSCs in vivo and in vitro; whereas its knockdown reversed these effects. Mechanistically, H19 promoted miR-675 expression and contributed to the competitively bounding of miR-675 and Adenomatous polyposis coli (APC), thus significantly activating the Wnt/ß-catenin pathway. The results suggested that HAMSCs promote osteogenic differentiation of HBMSCs via H19/miR-675/APC pathway, and supply a potential target for the therapeutic treatment of bone-destructive diseases.

4.
Environ Pollut ; 263(Pt A): 114554, 2020 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-32305800

RESUMO

In recent years, antibiotic pollution has become worse, especially in China. In this study, the ecotoxicological effects of four frequently used antibiotics with different lipophilic degrees (log Kow) (sulfadiazine (SD), sulfamethazine (SM2), enrofloxacin (ENR), and norfloxacin (NOR)) at four concentrations of 1, 5, 20, and 50 mg L-1 were examined using batch cultures of green alga Chlorella vulgaris and cyanobacterium Chrysosporum ovalisporum for 16 days based on changes in chlorophyll fluorescence parameters (chl a, Fv/Fm, and ΦPSII) and responses of the antioxidant system. Besides, the antibiotics removal efficiencies of the two microalgae were investigated. Sulfonamides (SD and SM2) had no significant inhibitory effect on the growth of C. ovalisporum, but had an inhibitory effect on C. vulgaris, whereas fluoroquinolones (ENR and NOR) significantly inhibited C. ovalisporum. The activities of superoxide dismutase, catalase, and glutathione reductase suggested that C. vulgaris was more tolerant to these antibiotics than C. ovalisporum. The increased malondialdehyde level in both algae indicated their tolerance against antibiotics. When compared with C. ovalisporum, C. vulgaris presented better capacity to remove antibiotics. In summary, the four antibiotics exerted time- or concentration-dependent ecotoxicological effects on the microalgae examined, whereas the microalgae could remove the antibiotics based on the log Kow of the antibiotics. The findings of this study contribute to effective understanding of the ecotoxicological effects of antibiotics and their removal by microalgae.

5.
Nano Lett ; 20(5): 3155-3159, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32286079

RESUMO

DNA origami holds an unprecedented capability on assembling metallic nanoparticles into designer plasmonic metamolecules of emerging properties, including surface-enhanced Raman scattering (SERS). SERS metamolecules were produced by positioning nanoparticles in close proximity to each other on a DNA origami template for Raman enhancement. In earlier reports, SERS metamolecules were generally assembled into clusters containing small number of nanoparticles (2, 3, or 4) and thus had limited programmability over SERS. Herein, we expanded the structural complexity of SERS metamolecules by increasing the number of nanoparticles and by arranging them into sophisticated configurations. DNA origami hexagon tile was used as the assembling template to fabricate clusters consisting of 6, 7, 12, 18, and 30+ metallic nanoparticles. Programmable SERS was realized via controlling the size, number, or spatial arrangement of nanoparticles. We believe this method offers a general platform for fabricating sophisticated nanodevices with programmable SERS that may be applied to a variety of fields including plasmonics, nanophotonics, and sensing.

8.
Curr Mol Med ; 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32282301

RESUMO

PURPOSE: Aiming at measuring levels of High-mobility group box-1 (HMGB1) and inflammation-related cytokines in the aqueous humor of patients with acute primary angle-closure glaucoma (APAG) and age-related cataract eyes (ARC). METHODS: Aqueous humor samples were obtained from 59 eyes of 59 Chinese subjects(APAG, 32 eyes; and ARC, 27eyes). The multiplex bead immunoassay technique was used to measure the Levels of HMGB1 and IL-8, IL-6, G-CSF, MCP-3, VEGF, sVEGFR-1, sVEFGR-2, TNF-α, PDGF and IL-10 in aqueous. The data of Patients' demographics and preoperative intraocular pressure (IOP) were also gathering for related analysis. RESULTS: The APAG group showed significantly elevated concentrations of HMGB1, IL-8, IL-6, G-CSF, VEGF, sVEGFR-1 and TNF-α than those in ARC group. Aqueous HMGB1 level correlated significantly with IOP, IL-8, IL6, G-CSF and sVEGFR-1 levels but not with age, TNF-α or VEGF levels. CONCLUSIONS: The aqueous level of HMGB1 is elevated in APAG and is associated with aqueous level of inflammation-related cytokines, suggesting an association between elevated levels of HMGB1, APAC and certain inflammatory modulators which, of course, should lead to further investigations in order to demonstrate cause and effect.

9.
Urol Oncol ; 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32241690

RESUMO

PURPOSE: To predict Gleason grade group (GG) upgrade in biopsy Gleason grade group 1 (GG1) prostate cancer (CaP) patients using surface-enhanced Raman spectroscopy (SERS). MATERIALS AND METHODS: Preoperative serum samples of patients with biopsy GG1 and subsequent radical prostatectomy were analyzed using SERS. The role of clinical variables and distinctive SERS spectra in the prediction of GG upgrade were evaluated. Principal component analysis and linear discriminant analysis (PCA-LDA) were used to manage spectral data and develop diagnostic algorithms. RESULTS: A total of 342 preoperative serum SERS spectra from 114 patients were obtained. SERS detected a higher level of circulating free nucleic acid bases and a lower level of lipids in patients with GG upgrade to GG3 and higher, presenting as SERS spectral peaks of 728 cm-1 and 1,655 cm-1, respectively. Both spectral peaks were independent predictors of GG upgrade and their addition to clinical predictors of PSA and positive core percent significantly improved predictive power of the logistic regression model with area under curve improved from 0.65 to 0.80 (P = 0.0045). Meanwhile, PCA-LDA diagnostic model based on serum SERS spectra showed a high accuracy of 91.2% in predicted groups and remained stable with a sensitivity, specificity, and accuracy of 65%, 97.3%, 86.0%, respectively when validated by leave-one-out cross-validation method. CONCLUSIONS: By analyzing preoperative serum samples, SERS combined with PCA-LDA model could be a promising tool for prediction of Gleason GG upgrade in biopsy GG1 CaP and assist in treatment decision-making in clinical practice.

10.
Int Urogynecol J ; 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32242276
11.
Artigo em Inglês | MEDLINE | ID: mdl-32212827

RESUMO

Aims: Neuroinflammation and oxidative stress are deemed the prime causes of brain injury after cerebral ischemia/reperfusion (I/R). Since the silent mating-type information regulation 2 homologue 3 (Sirt3) pathway plays an imperative role in protecting against neuroinflammation and oxidative stress, it has been verified as a target to treat ischemia stroke. Therefore, we attempted to seek novel Sirt3 agonist and explore its underlying mechanism for stroke treatment both in vivo and in vitro. Results: Trilobatin (TLB) not only dramatically suppressed neuroinflammation and oxidative stress injury after middle cerebral artery occlusion in rats, but also effectively mitigated oxygen and glucose deprivation/reoxygenation injury in primary cultured astrocytes. These beneficial effects, along with the reduced proinflammatory cytokines via suppressing Toll-like receptor 4 (TLR4) signaling pathway, lessened oxidative injury via activating nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways, in keeping with the findings in vivo. Intriguingly, the TLB-mediated neuroprotection on cerebral I/R injury was modulated by reciprocity between TLR4-mediated neuroinflammatory responses and Nrf2 antioxidant responses as evidenced by molecular docking and silencing TLR4 and Nrf2, respectively. Most importantly, TLB not only directly bonded to Sirt3 but also increased Sirt3 expression and activity, indicating that Sirt3 might be a promising therapeutic target of TLB. Innovation: TLB is a naturally occurring Sirt3 agonist with potent neuroprotective effects via regulation of TLR4/nuclear factor-kappa B and Nrf2/Kelch-like ECH-associated protein 1 (Keap-1) signaling pathways both in vivo and in vitro. Conclusion: Our findings indicate that TLB protects against cerebral I/R-induced neuroinflammation and oxidative injury through the regulation of neuroinflammatory and oxidative responses via TLR4, Nrf2, and Sirt3, suggesting that TLB might be a promising Sirt3 agonist against ischemic stroke.

12.
Nano Lett ; 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32202795

RESUMO

Reduced dimensional lead halide perovskites (RDPs) have attracted great research interest in diverse optical and optoelectronic fields. However, their poor stability is one of the most challenging obstacles prohibiting them from practical applications. Here, we reveal that ultrastable laurionite-type Pb(OH)Br can spontaneously encapsulate the RDPs in their formation solution without introducing any additional chemicals, forming RDP@Pb(OH)Br core-shell microparticles. Interestingly, the number of the perovskite layers within the RDPs can be conveniently and precisely controlled by varying the amount of CsBr introduced into the reaction solution. A single RDP@Pb(OH)Br core-shell microparticle composed of RDP nanocrystals with different numbers of perovskite layers can be also prepared, showing different colors under different light excitations. More interestingly, barcoded RDP@Pb(OH)Br microparticles with different parts emitting different lights can also be prepared. The morphology of the emitting microstructures can be conveniently manipulated. The RDP@Pb(OH)Br microparticles demonstrate outstanding environmental, chemical, thermal, and optical stability, as well as strong resistance to anion exchange processes. This study not only deepens our understanding of the reaction processes in the extensively used saturation recrystallization method but also points out that it is highly possible to dramatically improve the performance of the optoelectronic devices through manipulating the spontaneous formation process of Pb(OH)Br.

13.
J Mol Histol ; 51(1): 89-97, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32065357

RESUMO

To examine the expression of P53-induced protein with a death domain (PIDD) at retina in animal model of optic nerve crush (ONC) and to investigate the role of PIDD in retinal glial activation and NF-κB activation induced by optic nerve damage, ONC animal model was established in Sprague-Dawley rats. PIDD has three isoforms (Isof); Western blot was performed to examine the expression of PIDD (Isof-1, Isof-2, and Isof-3, respectively) in retina at different time points after ONC. Retinal glial activation is closely associated with retinal neuronal death and is monitored by the expression of GFAP+ glial cells and IBA1+ microglia, then activated microglia leads to inflammatory cytokine production. NF-kB activation in glial cells also can promote neuronal death. In our study, the role of PIDD in retinal glial activation and NF-kB activation was investigated with PIDD inhibition selectively. PIDD expression (Isof-1 and Isof-3) was dramatically increased, and peaked at 3 days after ONC, while Isof-2 did not show any difference. In the ONC animal model, the number of GFAP+ glial cells and IBA1+ microglia in retinal layers was increased significantly, inflammatory cytokine production was upregulated, and NF-κB in glial cell was also activated. Moreover, those responses induced by optic nerve damage were attenuated with PIDD inhibition, which indicated that PIDD could regulate retinal glial activation, neuro-inflammation, and NF-κB activation. These results provided the direct demonstration that the PIDD (Isof-1and Isof-3) was overexpressed in retina after ONC, and PIDD may be involved in retinal neurodegenerative diseases by regulating retinal glial activation and NF-κB activation.

14.
Phys Rev Lett ; 124(3): 038003, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-32031851

RESUMO

Lotus leaves floating on water usually experience short-wavelength edge wrinkling that decays toward the center, while the leaves growing above water normally morph into a global bending cone shape with long rippled waves near the edge. Observations suggest that the underlying water (liquid substrate) significantly affects the morphogenesis of leaves. To understand the biophysical mechanism under such phenomena, we develop mathematical models that can effectively account for inhomogeneous differential growth of floating and freestanding leaves to quantitatively predict formation and evolution of their morphology. We find, both theoretically and experimentally, that the short-wavelength buckled configuration is energetically favorable for growing membranes lying on liquid, while the global buckling shape is more preferable for suspended ones. Other influencing factors such as the stem or vein, heterogeneity, and dimension are also investigated. Our results provide a fundamental insight into a variety of plant morphogenesis affected by water foundation and suggest that such surface instabilities can be harnessed for morphology control of biomimetic deployable structures using substrate or edge actuation.


Assuntos
Lotus/crescimento & desenvolvimento , Modelos Biológicos , Água/química , Fenômenos Biofísicos , Lotus/anatomia & histologia , Morfogênese , Folhas de Planta/anatomia & histologia , Folhas de Planta/crescimento & desenvolvimento
16.
Theor Appl Genet ; 133(5): 1467-1489, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31965233

RESUMO

KEY MESSAGE: Epigenetic regulation has been implicated in the control of multiple agronomic traits in maize. Here, we review current advances in our understanding of epigenetic regulation, which has great potential for improving agronomic traits and the environmental adaptability of crops. Epigenetic regulation plays vital role in the control of complex agronomic traits. Epigenetic variation could contribute to phenotypic diversity and can be used to improve the quality and productivity of crops. Maize (Zea mays L.), one of the most widely cultivated crops for human food, animal feed, and ethanol biofuel, is a model plant for genetic studies. Recent advances in high-throughput sequencing technology have made possible the study of epigenetic regulation in maize on a genome-wide scale. In this review, we discuss recent epigenetic studies in maize many achieved by Chinese research groups. These studies have explored the roles of DNA methylation, posttranslational modifications of histones, chromatin remodeling, and noncoding RNAs in the regulation of gene expression in plant development and environment response. We also provide our future prospects for manipulating epigenetic regulation to improve crops.

17.
IUBMB Life ; 72(2): 296-304, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31509344

RESUMO

Human adipose-derived stem cells (HASCs) represent pluripotent cells capable of differentiating into the bone tissue. Meanwhile, human amnion-derived mesenchymal stem cells (HAMSCs) could cause mesenchymal stem cells to differentiate into the bone tissue. This work assessed the osteogenic effects exerted by HAMSCs on the potential of HASCs to form bone cells. Cell growth was evaluated flow-cytometrically. Differentiation into osteoblasts and mineral formation were assessed by chromogenic alkaline phosphatase activity substrate assay and Alizarin red S staining. Adiponectin (APN), the adipocytokine secreted by adipocytes, was evaluated by enzyme-linked immunosorbent assay. In this study, HAMSCs concentration-dependently induced growth, osteoblastic differentiation, and APN excretion in HASCs. Mechanistically, immunofluorescence and immunoblot revealed HAMSCs promoted cytosolic translocation of leucine zipper motif (APPL1) from the nucleus and induced extracellular signaling-regulated kinase 1/2 (ERK1/2) phosphorylation in HASCs. Furthermore, HAMSC effects were markedly blunted by pretreatment with APPL1 siRNA and U0126, an ERK1/2 signaling inhibitor with high selectivity. These results suggested that APN excretion is not suppressed by APPL1 knockdown in HASCs, but by ERK1/2 inhibition. These findings collectively indicate that HAMSCs induce the osteogenesis of HASCs by promoting APN excretion through APPL1-ERK1/2 activation.

18.
Nat Biomed Eng ; 4(2): 159-171, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31659307

RESUMO

Mechanical mismatches between implanted electronics and biological tissues can lead to inaccurate readings and long-term tissue damage. Here, we show that functionalized multi-walled carbon nanotubes twisted into helical fibre bundles that mimic the hierarchical structure of muscle can monitor multiple disease biomarkers in vivo. The flexible fibre bundles are injectable, have a low bending stiffness and display ultralow stress under compression. As proof-of-concept evidence of the sensing capabilities of these fibre bundles, we show that the fibre bundles enable the spatially resolved and real-time monitoring of H2O2 when implanted in tumours in mice, and that they can be integrated with a wireless transmission system on an adhesive skin patch to monitor calcium ions and glucose in the venous blood of cats for 28 d. The versatility of the helical fibre bundles as chemically functionalized electrochemical sensors makes them suitable for multiple sensing applications in biomedicine and healthcare.

19.
Cytokine ; 126: 154924, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31864100

RESUMO

AIMS: At present, there are few studies on the relationship between circulating irisin levels and gestational diabetes mellitus (GDM), and the results are inconsistent. Therefore, this study conducts a systematic review and meta-analysis to comprehensively discuss the role of irisin in the occurrence and development of GDM. METHODS: We searched the articles on the relationship between GDM and circulating irisin levels up to September 2019, using the CNKI, WANFANG-DATA, PubMed and the Web of Science databases. RESULTS: Twenty two articles including 3563 participants were selected in the meta-analysis. Meta-analysis found the blood irisin levels for GDM group were significantly lower than that for control group during pregnancy(SMD = -0.88, 95%CI: -1.34, -0.42, P < 0.001). However, there was no significant difference of irisin levels in the postpartum blood and cord blood between the two groups (SMD = -1.44, 95 %CI: -3.79, 0.92, P = 0.23; SMD = -0.17, 95 %CI: -0.59, 0.25, P = 0.42, respectively). CONCLUSIONS: Compared with the control group, irisin levels in the GDM group during pregnancy are lower. However, it is no significant difference of irisin levels in the postpartum blood and cord blood. Irisin may play an important role in the occurrence and development of GDM, which needs further research to demonstrate.

20.
Int Immunopharmacol ; 78: 106060, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31841757

RESUMO

Overwhelming inflammation and extensive alveolar-endothelial injury are characteristic pathological features of acute respiratory distress syndrome (ARDS)). MicroRNAs are involved in the regulation of a variety of cellular processes including endothelial damage and inflammatory responses. However, little is known about their function and the molecules regulating lung microvascular endothelial injury. Here, we determined the levels of microRNA-92a (miR-92a) in lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cells (HPMECs). We found that miR-92a expression was greater in HPMECs treated with LPS than in control cells. Inhibition of miR-92a through transfection with a miR-92a inhibitor significantly increased HPMECs migration, enhanced tube formation, and improved endothelial cell barrier dysfunction. Inhibition of miR-92a ameliorated the inflammatory response by decreasing the release of the proinflammatory factors IL-6 and TNF-α. In addition, integrin α5 (ITGA5) was found to be a target gene of miR-92a in LPS-induced endothelial barrier dysfunction. Western blot analysis showed that inhibition of miR-92a may ameliorate endothelial barrier dysfunction by activating the PI3K/Akt signaling pathway. Together, these results reveal an important role of miR-92a in LPS-induced endothelial barrier dysfunction, and suggest that miR-92a may have potential as a prognostic indicator and a future target for the treatment of acute lung injury (ALI)/ARDS.

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