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1.
Invest Ophthalmol Vis Sci ; 61(2): 14, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32049344

RESUMO

Purpose: Experimental access to specific cell subtypes is essential for deciphering the complexity of retinal networks. Here, we characterized the selective labeling, caused by ectopic transgene expression, of two atypical retinal neurons in the ChAT-Channelrhodopsin-2 (ChR2)-EYFP mouse. Methods: Retinal sections and flat-mounts were prepared for double-staining immunohistochemistry with antibodies against EYFP and various neuronal markers. Sagittal/coronal brain slices were made to visualize EYFP signals in central nuclei. Whole-cell recordings were conducted to test the functionality of ChR2. Results: Two populations of EYFP-positive retinal cells were observed. The inner nuclear layer (INL)-located one (type I cell) distributed regularly throughout the entire retina, whereas the ganglion cell layer (GCL)-residing one (type II cell) was restricted ventrally. None of them was cholinergic, as evidenced by the complete absence of ChAT immunoreactivity. Type I cells were immunolabeled by the amacrine marker syntaxin. However, the vast majority of them were neither positive to GABA/GAD65, nor to GlyT1/glycine, suggesting that they were non-GABAergic non-glycinergic amacrine cells (nGnG ACs), which was confirmed by double-labeling with the nGnG AC marker PPP1R17. Type II cells were immunopositive to melanopsin, but not to Brn3a or Brn3b. They possessed dendrites stratifying in the outermost inner plexiform layer (IPL) and axons projecting to the suprachiasmatic nucleus (SCN) rather than the olivary pretectal nucleus (OPN), suggesting that they belonged to a Brn3b-negative subset of M1-type intrinsically photosensitive retinal ganglion cells (ipRGCs). Glutamatergic transmission-independent photocurrents were elicited in EYFP-positive cells, indicating the functional expression of ChR2. Conclusions: The ChAT-ChR2-EYFP retina exhibits ectopic, but functional, transgene expression in nGnG ACs and SCN-innervating M1 ipRGCs, thus providing an ideal tool to achieve efficient labeling and optogenetic manipulation of these cells.

2.
Int J Mol Sci ; 21(4)2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32054031

RESUMO

Lung cancer is one of the most malignant cancers around the world, with high morbidity and mortality. Metastasis is the leading cause of lung cancer deaths and treatment failure. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs), two groups of small non-coding RNAs (nc-RNAs), are confirmed to be lung cancer oncogenes or suppressors. Transforming growth factor-ß (TGF-ß) critically regulates lung cancer metastasis. In this review, we summarize the dual roles of miRNAs and lncRNAs in TGF-ß signaling-regulated lung cancer epithelial-mesenchymal transition (EMT), invasion, migration, stemness, and metastasis. In addition, lncRNAs, competing endogenous RNAs (ceRNAs), and circular RNAs (circRNAs) can act as miRNA sponges to suppress miRNAs, thereby mediating TGF-ß signaling-regulated lung cancer invasion, migration, and metastasis. Through this review, we hope to cast light on the regulatory mechanisms of miRNAs and lncRNAs in TGF-ß signaling-regulated lung cancer metastasis and provide new insights for lung cancer treatment.

3.
Photodiagnosis Photodyn Ther ; : 101663, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31945549

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the third most common malignant tumor worldwide. Photodynamic therapy (PDT) is an emerging modality for the treatment of solid tumors. Sinoporphyrin sodium (DVDMS) is a new photosensitizer with good therapeutic killing effects on cancer cells. Recent findings have shown that microRNAs play important roles in many biological processes. However, the functions of microRNAs in DVDMS-induced PDT remain largely unclear. MATERIALS AND METHODS: Proteins involved in endoplasmic reticulum (ER) stress and apoptosis of CX-1 cells treated with DVDMS-PDT were examined by Western blotting and cell viability assays. 15 candidate miRNAs targeting RNA-dependent protein kinase-like ER kinase (PERK) were screened and verified using the TargetScan, miRWalk and miRDB databases. The downstream pathways of candidate miRNAs with high scores were studied by cell transfection, qRT-PCR, Western blotting and dual-luciferase reporter assays. The subcellular location of DVDMS was confirmed by laser confocal microscopy. RESULTS: DVDMS-PDT induced apoptosis via elevated ER stress and activation of the PERK/ATF4/CHOP/caspase cascade pathway in CX-1 cells. The endoplasmic reticulum was involved in the subcellular accumulation of DVDMS in CX-1 cells. Dual-luciferase reporting experiment confirmed that a direct crosslinking between miR-7112-3p and PERK. In addition, miR-7112-3p was highly expressed in CRC tissues compared with peripheral tissues. CONCLUSION: Our work showed that miR-7112-3p directly targeted PERK and further regulated PERK/ATF4/CHOP/caspase cascade pathway, resulting in enhanced apoptosis in CX-1 cells treated with DVDMS-PDT.

4.
Stroke ; : STROKEAHA119027981, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31964286

RESUMO

Background and Purpose- Poststroke autonomic dysfunction portended an unfavorable prognosis. We investigated whether blood pressure variability (BPV), heart rate variability, and baroreflex sensitivity might predict stroke functional outcome. Methods- We calculated BPV, heart rate variability, baroreflex slope, and baroreflex effectiveness index from a 5-minute beat-to-beat blood pressure and heart rate monitoring within 7 days from the stroke onset. We compared the parameters between patients with a good outcome (modified Rankin Scale score, 0-2) and those with a poor outcome. Results- Among 142 patients (mean age, 63.9±10.2 years; 88.0% men), functional outcome was good in 112 (78.9%) and poor in 30 (21.1%). There were significant differences in admission National Institutes of Health Stroke Scale, prior stroke, high-frequency systolic BPV, low/high-frequency ratio of BPV, baroreflex sensitivity-up, and baroreflex sensitivity-total between the 2 groups (all P<0.05). In multivariate analysis, National Institutes of Health Stroke Scale (OR, 1.672 [95% CI, 1.316-2.125]; P<0.001), low/high-frequency ratio of systolic BPV (OR, 0.493 [95% CI, 0.250-0.973]; P=0.041), and baroreflex effectiveness index-down (OR, 0.958 [95% CI, 0.924-0.992]; P=0.017) independently predicted a poor functional outcome. Conclusions- A decreased low/high-frequency ratio of systolic BPV and impaired baroreflex sensitivity predicted an unfavorable stroke outcome, in addition to the established prognostic factor such as the National Institutes of Health Stroke Scale.

5.
Brain Res ; 1726: 146537, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31672473

RESUMO

Higher visual centers could modulate visually-guided ocular growth, in addition to local mechanisms intrinsic to the eye. There is evidence that such central modulations could be species (even subspecies)-dependent. While the mouse has recently become an important experimental animal in myopia studies, it remains unclear whether and how visual centers modulate refractive development in mice, an issue that was examined in the present study. We found that optic nerve crush (ONC), performed at P18, could modify normal refractive development in the C57BL/6 mouse raised in normal visual environment. Unexpectedly, sham surgery caused a steeper cornea, leading to a modest myopic refractive shift, but did not induce significant changes in ocular axis length. ONC caused corneal flattening and re-calibrated the refractive set-point in a bidirectional manner, causing significant myopic (<-3 D, 54.5%) or hyperopic (>+3 D, 18.2%) shifts in refractive error in most (totally 72.7%) animals, both due to changes in ocular axial length. ONC did not change the density of dopaminergic amacrine cells, but increased retinal levels of dopamine and DOPAC. We conclude that higher visual centers are likely to play a role in fine-tuning of ocular growth, thus modifying refractive development in the C57BL/6 mouse. The changes in refractive error induced by ONC are accounted for by alternations in multiple ocular dimensions, including corneal curvature and axial length.

6.
World J Clin Cases ; 7(22): 3734-3741, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31799298

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is the world's sixth most common malignant tumor and the third cause of cancer death. Although great progress has been made in hepatectomy, it is still associated with a certain degree of risk of post-hepatectomy liver failure (PHLF), which extends the length of hospital stay and remains the leading cause of postoperative death. Studies have shown that assessment of hepatic functional reserve before hepatectomy is beneficial for reducing the incidence of PHLF. AIM: To assess the value of model for end-stage liver disease (MELD) score combined with standardized future liver remnant (sFLR) volume in predicting PHLF in patients undergoing hepatectomy for HCC. METHODS: This study was attended by 238 patients with HCC who underwent hepatectomy between January 2015 and January 2018. Discrimination of sFLR volume, MELD score, and sFLR/MELD ratio to predict PHLF was evaluated according to the area under the receiver operating characteristic curve. RESULTS: The patients were divided into two groups according to whether PHLF occurred after hepatectomy. The incidence of PHLF was 8.4% in our research. The incidence of PHLF increased with the decrease in sFLR volume and the increase in MELD score. Both sFLR volume and MELD score were considered independent predictive factors for PHLF. Moreover, the cut-off value of the sFLR/MELD score to predict PHLF was 0.078 (P < 0.001). This suggests that an sFLR/MELD ≥ 0.078 indicates a higher incidence of PHLF than an sFLR/MELD < 0.078. CONCLUSION: MELD combined with sFLR is a reliable and effective PHLF predictor, which is superior to MELD score or sFLR volume alone.

7.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(6): 872-877, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31880120

RESUMO

OBJECTIVE: To study the relationship between the copy numbers of repetitive units at variable number tandem repeat (VNTR) loci of Mycobacterium tuberculosis complex (MTBC) with its diversity of protein profiles. METHODS: The MTBC strains were subjected to genotyping using multiple locus variable number tandem repeat analysis (MLVA). Also, the principal component analysis (PCA) was performed for bacterial protein profiles of MTBC using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The relationship between the polymorphism of VNTR loci and PCA clustering was analyzed. RESULTS: A total of 157 MTBC strains were collected. 146 MTBC strains (MS identification score values ≥1.700) were performed PCA and three clusters, clusterⅠ(61 strains), clusterⅡ(26 strains) and cluster Ⅲ(59 strains), were generated. Polymorphic diversities were observed in 24 VNTR loci, among them, 7 were highly various, 7 were moderately, and 10 were low various. The polymorphism of Mtub39, QUB26 and QUB4156 loci were correlated with the results of MALDI-TOF MS clustering (P=0.000, P=0.035, P=0.017). CONCLUSION: The polymorphism of Mtub39, QUB26 and QUB4156 loci in MTBC was correlated with the difference of MALDI-TOF MS protein profiles, suggesting that these loci may play a role in regulating the composition of protein profiles of MTBC strains.


Assuntos
Repetições Minissatélites , Mycobacterium tuberculosis , Genótipo , Polimorfismo Genético , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
8.
Gastroenterol Res Pract ; 2019: 3682836, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772570

RESUMO

The very low birth weight (VLBW) infant is at great risk for marked dysbiosis of the gut microbiota. In the present study, a total of 36 VLBW infants were randomly divided into two groups, who were treated with combined probiotics and placebo, and 72 fecal specimens on days 14 and 28 of life were collected from them. Finally, 32 fecal specimens extracted from 16 preterm VLBW infants were qualified and analyzed using 16S rRNA gene sequencing. The primary outcome was to evaluate the change of gut microbiota in VLBW infants after combined probiotic supplement. The secondary outcome was to analyze the correlation gut microbial composition and levels of cytokines. We found that probiotic treatment, but not placebo, decreased the α-diversity of gut microbiota in VLBW infants. At the phylum level, probiotic treatment strongly increased the abundance of Firmicutes, whereas that of Proteobacteria was significantly reduced. At the family level, Streptococcaceae and Lactobacillaceae became prevalent after probiotic treatment, while the relative abundance of Enterobacteriaceae was reduced in the meantime. Most notably, significant correlations were observed between Lactobacillaceae abundance and serum cytokine levels. Further studies are required to shed more light on the characteristics of gut microbiota of VLBW neonates. And the modulation of microbiota should be considered to improve the survival rate of VLBW infants.

9.
Cell Death Dis ; 10(11): 829, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685807

RESUMO

Metastasis is a well-known poor prognostic factor in cancer. However, the mechanisms how long non-coding RNAs (lncRNAs) regulate metastasis in colorectal cancer (CRC) remain largely unknown. Besides, tumor-associated macrophages (TAMs) play an important role in tumor progression, yet the contribution of lncRNA-mediated crosstalk between TAMs and CRC cells to tumor progression is not well understood. In this study, we report that lncRNA RPPH1 was significantly upregulated in CRC tissues, and the RPPH1 overexpression was associated with advanced TNM stages and poor prognosis. RPPH1 was found to promote CRC metastasis in vitro and in vivo. Mechanistically, RPPH1 induced epithelial-mesenchymal transition (EMT) of CRC cells via interacting with ß-III tubulin (TUBB3) to prevent its ubiquitination. Furthermore, CRC cell-derived exosomes transported RPPH1 into macrophages which mediate macrophage M2 polarization, thereby in turn promoting metastasis and proliferation of CRC cells. In addition, exosomal RPPH1 levels in blood plasma turned out to be higher in treatment-naive CRC patients but lower after tumor resection. Compared to CEA and CA199, exosomal RPPH1 in CRC plasma displayed a better diagnostic value (AUC = 0.86). Collectively, RPPH1 serves as a potential therapeutic and diagnostic target in CRC.

10.
Org Biomol Chem ; 17(44): 9567-9572, 2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31686070

RESUMO

Inspired by the chemistry and biology of chromone and oxindole derivatives, herein we report the first example of thermal-mediated [1,3]-hydrogen transfer as the key step for the efficient synthesis of oxindole-chromone hybrid collections 2, which avoids additional catalyst and solvent conditions. All the oxindole-chromones 2 are smoothly obtained in >99% yields in all cases, avoiding column chromatography purification. In particular, the products 2 can act as potential synthons for further elaboration in structural diversity, which might be valuable in organic and medicinal chemistry.

11.
Fish Shellfish Immunol ; 95: 287-296, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31669895

RESUMO

Disulfide bonds are fundamental in establishing Ig structure and maintaining Ig biological function. Here, we analysed disulfide bonds and free cysteine in three grass carp IgM isoforms (monomeric, dimeric/trimeric, and tetrameric IgM) by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The results revealed that Cys574 residue status at the C-terminal tail differed substantially in monomeric IgM in comparison with polymeric IgM, Cys574 was found as free thiol in monomeric IgM, while it formed disulfide linkages in dimeric/trimeric and tetrameric IgM. Five intra-chain disulfide bonds in the CH1~CH4 and CL1 domains, as well as one H-H and one H-L inter-chain disulfide linkages, were also observed and shown identical connectivity in monomeric, dimeric/trimeric, and tetrameric IgM. These findings represent the first experimental assignments of disulfide linkages of grass carp IgM and reveal that grass carp IgM isoform formation is due to alternative disulfide bonds connecting the Cys574 residue at the C-terminal tail.

12.
Chem Commun (Camb) ; 55(93): 14003-14006, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31690910

RESUMO

The first example of a bifunctional donor-donor 3C synthon in situ from activated methine (methyleneindolinone and methylenebenzofuranone) with nitromethane through a [2+1] Michael addition, which further directed the following organocascade Michael/Henry cycloaddition reaction in a one-pot operation is developed, serving as a fruitful strategy for facile access to optically active and structurally diverse hexahydroxanthones with up to six contiguous stereocenters, including a quaternary one. A series of diversely functionalized products are smoothly obtained with up to 76% yield, >20 : 1 d.r. and 98% ee from simple and readily available starting materials. In addition, this is the first example of 3-formyl chromone as an acceptor-acceptor 3C building block, and also the first asymmetric catalytic construction of six vicinal stereogenic centers on a hexahydroxanthone scaffold.

13.
Cancers (Basel) ; 11(11)2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31744046

RESUMO

As a highly heterogeneous malignancy, breast cancer (BC) has become the most significant threat to female health. Distant metastasis and therapy resistance of BC are responsible for most of the cases of mortality and recurrence. Distant metastasis relies on an array of processes, such as cell proliferation, epithelial-to-mesenchymal transition (EMT), mesenchymal-to-epithelial transition (MET), and angiogenesis. Long non-coding RNA (lncRNA) refers to a class of non-coding RNA with a length of over 200 nucleotides. Currently, a rising number of studies have managed to investigate the association between BC and lncRNA. In this study, we summarized how lncRNA has dual effects in BC metastasis by regulating invasion, migration, and distant metastasis of BC cells. We also emphasize that lncRNA has crucial regulatory effects in the stemness and angiogenesis of BC. Clinically, some lncRNAs can regulate chemotherapy sensitivity in BC patients and may function as novel biomarkers to diagnose or predict prognosis for BC patients. The exact impact on clinical relevance deserves further study. This review can be an approach to understanding the dual effects of lncRNAs in BC, thereby linking lncRNAs to quasi-personalized treatment in the future.

14.
Bioorg Med Chem ; 27(22): 115109, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615696

RESUMO

A series of structurally diverse chrysin-chromene-spirooxindole hybrids were designed, synthesized via a Knoevenagel/Michael/cyclization of chrysin and isatylidene malononitrile derivatives through utilizing a hybrid pharmacophore approach. The newly synthesized compounds were evaluated for their in vitro anticancer activity, and most of the compounds showed stronger anti-proliferative activity than parent compound chrysin. In particular, compound 3e had the highest cytotoxicity towards A549 cells (IC50 = 3.15 ±â€¯0.51 µM), and had better selectivity in A549 cells and normal MRC-5 cells. Furthermore, compound 3e could significantly inhibit the proliferation and migration of A549 cells in a dose-dependent manner, as well as induce the apoptosis possibly through mitochondria-mediated caspase-3/8/9 activation and multi-target co-regulation of the p53 signaling pathway. Thus, our results provide in vitro evidence that compound 3e may be a potential candidate for the development of new anti-tumour drugs.

15.
Kidney Blood Press Res ; 44(6): 1339-1351, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31661692

RESUMO

AIM: This study aimed to investigate the effect of norcantharidin (NCTD) on human mesangial cells (HMCs) apoptosis in vitro and further examine its molecular mechanism. METHODS: HMCs were divided into 5 groups: control group, 25% fetal bovine serum (FBS)-treated group, and NCTD groups (NCTD [2.5, 5 and 10 µg/mL] + 25% FBS, respectively). Cell proliferation was determined by MTT assay, while apoptosis was evaluated by Hoechest 33258 staining, the level of cytochrome c, immunohistochemistry, and apoptotic-related proteins/gene expression. RESULTS: Cell viability was inhibited in NCTD-treated HMCs in a dose-dependent manner. The number of apoptotic cells and the content of cytochrome c were significantly increased by NCTD treatment but that of mitochondrial membrane was decreased. Moreover, the expression of bcl-2 and caspase-3 was prompted by NCTD, but the expression of bax, MMP-2, and MMP-9 in 25% FBS-treated HMCs was inhibited. In addition, NCTD markedly unregulated the expression of apoptosis-related gene/protein, including p-Erk1/2, phosphorylated-Jun N-terminal kinase (JNK), p-p38, and p53. CONCLUSION: NCTD enhances 25% FBS-treated HMC apoptosis in vitro, and this effect may be attributed to the modulation of the ERK, JNK, and p38 mitogen-activated protein kinase signaling pathways.

16.
J Stroke Cerebrovasc Dis ; 28(12): 104413, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31582272

RESUMO

BACKGROUND: Poststroke depression (PSD) is one of the most common complications after ischemic stroke, and periodontitis is associated with depression. However, whether severe periodontitis is associated with early-onset PSD status remains unknown. In this study, we aimed to investigate whether there is an association between severe periodontitis and PSD status in acute ischemic stroke patients. MATERIAL AND METHODS: We recruited 202 acute ischemic stroke patients within 7 days after stroke onset. Pocket depth and clinical attachment loss were assessed by oral examination to define the severe periodontitis. On the basis of diagnosis of PSD status according to DSM-5 criteria and a 24-item Hamilton Depression Rating Scale score greater than or equal to 8 within 2 weeks after stroke onset, we stratified patients into PSD status or non-PSD status groups and identified the independent predictors for the development of PSD status in multivariate logistic analysis. RESULTS: 77 (38.1%) patients were diagnosed as early-onset PSD status. PSD status group showed more severe periodontitis, lower income, lower Barthel Index (BI) score and Montreal Cognitive Assessment score, higher National Institutes of Health Stroke Scale score and modified Rankin scale (mRS) score compared with non-PSD status group. Multivariate logistic regression showed that severe periodontitis (odds ratio 2.401) and NIHSS score (>4, odds ratio 2.130) were independent predictors for early-onset PSD status. CONCLUSIONS: Severe periodontitis is found to be an important independent predictor of early-onset PSD status in patients with acute ischemic stroke, in addition to the well-known prognostic factors such as nonminor stroke assessed by NIHSS greater than 4.

17.
IEEE Trans Knowl Data Eng ; 31(7): 1397-1411, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31564814

RESUMO

Outsourcing data and computation to cloud server provides a cost-effective way to support large scale data storage and query processing. However, due to security and privacy concerns, sensitive data (e.g., medical records) need to be protected from the cloud server and other unauthorized users. One approach is to outsource encrypted data to the cloud server and have the cloud server perform query processing on the encrypted data only. It remains a challenging task to support various queries over encrypted data in a secure and efficient way such that the cloud server does not gain any knowledge about the data, query, and query result. In this paper, we study the problem of secure skyline queries over encrypted data. The skyline query is particularly important for multi-criteria decision making but also presents significant challenges due to its complex computations. We propose a fully secure skyline query protocol on data encrypted using semantically-secure encryption. As a key subroutine, we present a new secure dominance protocol, which can be also used as a building block for other queries. Furthermore, we demonstrate two optimizations, data partitioning and lazy merging, to further reduce the computation load. Finally, we provide both serial and parallelized implementations and empirically study the protocols in terms of efficiency and scalability under different parameter settings, verifying the feasibility of our proposed solutions.

18.
Int J Endocrinol ; 2019: 5219782, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31662747

RESUMO

Background: Diabetes is a progressive metabolic disease characterized by hyperglycemia. Functional impairment of islet ß cells can occur to varying degrees. This impairment can initially be compensated for by proliferation and metabolic changes of ß cells. Cell division control protein 42 (Cdc42) and the microRNA (miRNA) miR-29 have important roles in ß-cell proliferation and glucose-stimulated insulin secretion (GSIS), which we further explored using the mouse insulinoma cell line MIN6. Methods: Upregulation and downregulation of miR-29a and Cdc42 were accomplished using transient transfection. miR-29a and Cdc42 expression was detected by real-time PCR and western blotting. MIN6 proliferation was detected using a cell counting kit assay. GSIS under high-glucose (20.0 mM) or basal-glucose (5.0 mM) stimulation was detected by enzyme-linked immunosorbent assay. The miR-29a binding site in the Cdc42 mRNA 3'-untranslated region (UTR) was determined using bioinformatics and luciferase reporter assays. Results: miR-29a overexpression inhibited proliferation (P < 0.01) and GSIS under high-glucose stimulation (P < 0.01). Cdc42 overexpression promoted proliferation (P < 0.05) and GSIS under high-glucose stimulation (P < 0.05). miR-29a overexpression decreased Cdc42 expression (P < 0.01), whereas miR-29a downregulation increased Cdc42 expression (P < 0.01). The results showed that the Cdc42 mRNA 3'-UTR is a direct target of miR-29a in vitro. Additionally, Cdc42 reversed miR-29a-mediated inhibition of proliferation and GSIS (P < 0.01). Furthermore, miR-29a inhibited ß-catenin expression (P < 0.01), whereas Cdc42 promoted ß-catenin expression (P < 0.01). Conclusion: By negatively regulating Cdc42 and the downstream molecule ß-catenin, miR-29a inhibits MIN6 proliferation and insulin secretion.

19.
Adv Mater ; 31(49): e1904329, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31538379

RESUMO

Surgical resection is the primary and most effective treatment for most patients with solid tumors. However, patients suffer from postoperative recurrence and metastasis. In the past years, emerging nanotechnology has led the way to minimally invasive, precision and intelligent oncological surgery after the rapid development of minimally invasive surgical technology. Advanced nanotechnology in the construction of nanomaterials (NMs) for precision imaging-guided surgery (IGS) as well as surgery-assisted synergistic therapy is summarized, thereby unlocking the advantages of nanotechnology in multimodal IGS-assisted precision synergistic cancer therapy. First, mechanisms and principles of NMs to surgical targets are briefly introduced. Multimodal imaging based on molecular imaging technologies provides a practical method to achieve intraoperative visualization with high resolution and deep tissue penetration. Moreover, multifunctional NMs synergize surgery with adjuvant therapy (e.g., chemotherapy, immunotherapy, phototherapy) to eliminate residual lesions. Finally, key issues in the development of ideal theranostic NMs associated with surgical applications and challenges of clinical transformation are discussed to push forward further development of NMs for multimodal IGS-assisted precision synergistic cancer therapy.

20.
Org Biomol Chem ; 17(36): 8369-8373, 2019 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-31486452

RESUMO

We report the first asymmetric iminium ion catalysis-enabled cascade cycloaddition reaction of bifunctional chromone-oxindole synthons and α,ß-unsaturated aldehydes. This allowed one quaternary and four tertiary contiguous stereogenic centers to be constructed in a single operation. A range of spirooxindole-hexahydroxanthone molecules are obtained with up to 62% yield, >20 : 1 dr and >99% ee. This reaction has not only provided a new approach for constructing hexahydroxanthone-fused scaffolds by utilizing asymmetric iminium ion catalysis, but also advanced the chemistry of diversity-oriented synthesis based on bifunctional chromone synthons.

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