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1.
Ecotoxicol Environ Saf ; 193: 110348, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32114240

RESUMO

Due to rapid advances in the era of electronic technologies, indium has played the important material for the production of liquid crystal display screens in the semiconductor and optoelectronic industries. The present study focuses on evaluating the toxic effects and related mechanisms of indium chloride (InCl3) on RAW264.7 macrophages. Cytotoxicity was induced by InCl3 in a concentration- and time-dependent manner. InCl3 had the ability to induce macrophage death through apoptosis rather than through necrosis. According to the cytokinesis-block micronucleus assay and alkaline single-cell gel electrophoresis assay, InCl3 induced DNA damage, also called genotoxicity, in a concentration-dependent manner. Cysteine-dependent aspartate-directed protease (caspase)-3, -8, and -9 were activated by InCl3 in a concentration-dependent manner. Mitochondria dysfunction and cytochrome c release from the mitochondria were induced by InCl3 in a concentration-dependent manner. Downregulation of BCL2 and upregulation of BAD were induced by InCl3 in a concentration-dependent manner. More, we proposed that InCl3 treatment generated reactive oxygen species (ROS) in a concentration-dependent manner. In conclusion, the current study revealed that InCl3 induced macrophage cytotoxicity, apoptosis, and genotoxicity via a mitochondria-dependent apoptotic pathway and ROS generation.

2.
World Neurosurg ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32200017

RESUMO

BACKGROUND: Dilatation of Virchow-Robin spaces (dVRS) have been described in the development of hydrocephalic syndromes. We report an unusual case of a Type III dVRS presenting as a mimic of normal pressure hydrocephalus (NPH), due to distortion at the level of the cerebral aqueduct. CASE DESCRIPTION: A 59-year-old female presented with mild traumatic brain injury and possible NPH, due to a history of progressive gait disturbance, recurrent falls and cognitive decline over a year, in the context of ventriculomegaly. Detailed structural imaging of the brain revealed multiple dilated cystic lesions consistent with VRS causing distortion at the level of the cerebral aqueduct. CSF examination was negative for infection. The patient was treated with endoscopic third ventriculostomy (ETV); at 12 months post-operatively, she demonstrated a sustained improvement in gait and stabilization of cognitive decline. CONCLUSIONS: This is an illustrative case of a subacute obstructive hydrocephalus due to a collection of periaqueductal dVRS, leading to an insidious clinical presentation mimicking NPH. We reviewed the literature for key clinical presentations and describe neuroanatomical considerations as well as primary treatment strategies. Various hydrocephalic syndromes may present with classic symptoms from Hakim's triad; such symptoms are not specific to idiopathic NPH. Both ETV and shunting may be effacious. In our case, dVRS may serve as both a cause of and compensatory mechanism in a subacute obstructive hydrocephalus of unknown etiology. Our case highlights the need to understand the neuroanatomy of aberrant CSF spaces in hydrocephalic syndromes. Further studies of dVRS would provide valuable insights into the pathogenesis of hydrocephalus.

3.
Environ Sci Technol ; 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32202770

RESUMO

Zinc isotope ratios in water and suspended particles (SP) were measured in the Pearl River Estuary (PRE), China. Site-to-site δ66Zn values in water varied by approximately 1.3‰ (i.e., -0.66‰ to 0.65‰ relative to IRMM-3702 in August 2017). There were larger variations in δ66Zn values in water collected from the east shore (i.e., -0.66‰ to 0.37‰) of the PRE close to industrialized areas, in comparison to those from the western shore (i.e., -0.23‰ to 0.13‰), indicating that the PRE was influenced by different Zn sources. The variations in δ66Zn values in water from estuarine locations were much larger than those collected from river mouths. Similarly, larger variations in δ66Zn values were observed in suspended particles (i.e., -1.45‰ to 0.63‰) relative to the water. Zinc isotopic differences (i.e., Δ66Zn‰) between particles and water were significantly (p < 0.05) and linearly correlated with Zn concentrations in particles between 0.8 and 10 µm in size at most of the estuary stations, suggesting that Zn partitioning between dissolved and particulate phases influences the observed differences in Zn isotope ratios. A significant (p < 0.0001) linear correlation between the predicted δ66Zn values (using variations in water salinities) vs observed δ66Zn values indicates that Zn isotope ratios in water in the PRE can be useful for predicting the mixing processes in the water.

4.
Cancer Res ; 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32098780

RESUMO

At the request of my authors, you must replace the abstract that is in your manuscript AND on SmartSubmit with the following version: Perineural invasion (PNI) is a common feature of pancreatic ductal adenocarcinoma (PDAC). Here, we investigated the effect of PNI on the microenvironment and how this affects PDAC progression. Transcriptome expression profiles of PDAC tissues with different PNI status were compared, and the intratumoral T cell density and levels of neurotransmitters in these tissues were assessed. PNI was associated with impaired immune responses characterized by decreased CD8+ T and Th1 cells, and increased Th2 cells. Acetylcholine levels were elevated in severe PNI. Acetylcholine impaired the ability of PDAC cells to recruit CD8+ T cells via HDAC1-mediated suppression of CCL5. Moreover, acetylcholine directly inhibited IFN-γ production by CD8+ T cells in a dose-dependent manner, and favored Th2 over Th1 differentiation. Furthermore, hyperactivation of cholinergic signaling enhanced tumor growth by suppressing the intratumoral T cell response in an orthotopic PDAC model. Conversely, blocking PNI with bilateral subdiaphragmatic vagotomy in tumor-bearing mice was associated with an increase in CD8+ T cells, an elevated Th1/Th2 ratio and improved survival. In conclusion, PNI-triggered cholinergic signaling favors tumor growth by promoting an immune-suppressive microenvironment characterized by impaired CD8+ T cell infiltration and a reduced Th1/Th2 ratio.

5.
Eur J Immunol ; 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31943150

RESUMO

CD5 is expressed on T cells and a subset of B cells (B1a). It can attenuate TCR signalling and impair CTL activation and is a therapeutic targetable tumour antigen expressed on leukemic T and B cells. However, the potential therapeutic effect of functionally blocking CD5 to increase T cell anti-tumour activity against tumours (including solid tumours) has not been explored. CD5 knockout mice show increased anti-tumour immunity: reducing CD5 on CTLs may be therapeutically beneficial to enhance the anti-tumour response. Here, we show that ex vivo administration of a function-blocking anti-CD5 MAb to primary mouse CTLs of both tumour-naïve mice and mice bearing murine 4T1 breast tumour homografts enhanced their capacity to respond to activation by treatment with anti-CD3/anti-CD28 MAbs or 4T1 tumour cell lysates. Furthermore, it enhanced TCR signalling (ERK activation) and increased markers of T cell activation, including proliferation, CD69 levels, IFN-γ production, apoptosis and Fas receptor and Fas ligand levels. Finally, CD5 function-blocking MAb treatment enhanced the capacity of CD8+ T cells to kill 4T1-mouse tumour cells in an ex vivo assay. These data support the potential of blockade of CD5 function to enhance T cell-mediated anti-tumour immunity.

6.
Sci Rep ; 10(1): 489, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949227

RESUMO

Soil nitrification via ammonia oxidation is a key ecosystem process in terrestrial environments, but little is known of how increasing irrigation of farmland soils with saline waters effects these processes. We investigated the effects of long-term irrigation with saline water on the abundances and community structures of ammonia-oxidizing bacteria (AOB) and archaea (AOA). Irrigation with brackish or saline water increased soil salinity (EC1:5) and NH4-N compared to irrigation with freshwater, while NO3-N, potential nitrification rates (PNR) and amoA gene copy numbers of AOA and AOB decreased markedly under irrigation regimes with saline waters. Moreover, irrigation with brackish water lowered AOA/AOB ratios. PNR was positively correlated with AOA and AOB amoA gene copy numbers across treatments. Saline and brackish water irrigation significantly increased the diversity of AOA, as noted by Shannon index values, while saline water irrigation markedly reduced AOB diversity. In addition, irrigation with brackish or fresh waters resulted in higher proportions of unclassified taxa in the AOB communities. However, irrigation with saline water led to higher proportions of unclassified taxa in the AOA communities along with the Candidatus Nitrosocaldus genus, as compared to soils irrigated with freshwater. AOA community structures were closely associated with soil salinity, NO3-N, and pH, while AOB communities were only significantly associated with NO3-N and pH. These results suggest that salinity was the dominant factor affecting the growth of ammonia-oxidizing microorganisms and community structure. These results can provide a scientific basis for further exploring the response mechanism of ammonia-oxidizing microorganisms and their roles in nitrogen transformation in alluvial grey desert soils of arid areas.

7.
Exp Anim ; 69(1): 45-53, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31391379

RESUMO

Ip3r1 encodes an inositol 1,4,5-trisphosphate-responsive calcium channel. Mutations in the IP3R1 gene in humans may cause Gillespie syndrome (GS) typically presents as fixed dilated pupils in affected infants, which was referred to as iris hypoplasia. However, there is no report of mice with Ip3r1 heterozygous mutations showing dilated pupils. Here, we report a new Ip3r1 allele with short-term dilated pupil phenotype derived from an N-ethyl-N-nitrosourea (ENU) mutagenesis screen. This allele carries a G5927A transition mutation in Ip3r1 gene (NM_010585), which is predicted to result in a C1976Y amino acid change in the open reading frame of IP3R1 (NP_034715). We named this novel Ip3r1 allele Ip3r1C1976Y. Histology and pharmacological tests show that the dilated pupil phenotype is a mydriasis caused by the functional defect in the iris constrictor muscles in Ip3r1C1976Y. The dilated pupil phenotype in Ip3r1C1976Y was referred to as mydriasis and excluding iris hypoplasia. IHC analysis revealed increased expression of BIP protein, the master regulator of unfolded protein response (UPR) signaling, in Ip3r1C1976Y mice that did not recover. This study is the first report of an Ip3r1 mutation being associated with the mydriasis phenotype. Ip3r1C1976Y mice represent a self-healing model that may be used to study the therapeutic approach for Ip3r1-related diseases.

8.
ACS Appl Mater Interfaces ; 12(1): 858-867, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31820629

RESUMO

Recently, metal-halide perovskites have emerged as a candidate for optoelectronic applications such as photodetectors. However, the poor device performance and instability have limited their future commercialization. Herein, we report the spontaneous growth of perovskite/N-rGO hybrid structures using a facile solution method and their applications for photodetectors. In the hybrid structures, perovskites were homogeneously wrapped by N-rGO sheets through strong hydrogen bonding. The strongly coupled N-rGOs facilitate the charge carrier transportation across the perovskite crystals but also distort the surface lattice of the perovskite creating a potential barrier for charge transfer. We optimize the addition of N-rGO in the hybrid structures to balance interfacial structural distortion and the intercrystal conductivity. High-performance photodetection up to 3 × 104 A/W, external quantum efficiency exceeding 105%, and detectivity up to 1012 Jones were achieved in the optimal device with the weight ratio between perovskites and N-rGO to be 8:1.5. The underlying mechanism behind the optimal N-rGO addition ratio in the hybrids has also been rationalized via time-resolved spectroscopic studies as a reference for future applications.

9.
Huan Jing Ke Xue ; 41(1): 420-429, 2020 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854945

RESUMO

A five year field experiment was conducted to evaluate the effect of continually returning cotton straw or biochar on microbial metabolic function and bacterial community composition of soil in a cotton field under drip irrigation conditions. The experiment involved three treatments:control (single application of chemical fertilizer, CK), cotton straw (returning of cotton straw plus chemical fertilizer application, ST), and biochar (returning of cotton straw biochar plus chemical fertilizer application, BC). The returning of cotton straw and biochar both significantly increased soil organic matter, total nitrogen, and available nutrients, but the effect of returning biochar was more significant. The carbon source metabolic activities of the soil in the ST treatment was the highest, followed by the BC treatment, which was significantly higher than of that in the CK treatment. The returning of cotton straw promoted the metabolism of carbohydrate and amine carbon sources, while biochar significantly increased the metabolism of polymer carbon sources. Compared with the CK treatment, the ST treatment significantly increased the phylum of Proteobacteria, Actinobacteria, Bacteroides, and the family of Xanthomonadaceae, Acidobacteriaceae, Microbacteriaceae, and Cytophagaceae. The BC treatment significantly increased the phylum of Acidobacteria, Gemmatimonadetes, Nitrospirae, and the family of Blastocatellaceae (subgroup 4), Gemmatimonadaceae, and Nitrosomonadaceae. The correlation analysis showed that there were significant positive correlations between the relative abundances of Xanthomonadaceae and Acidobacteriaceae and the carbon source metabolic activities of carbohydrates, amino acids, carboxylic acids, and amines. The relative abundances of Microbacteriaceae and Cytophagaceae were positively correlated with carbohydrates and amines. There was a significant positive correlation between the relative abundance of Blastocatellaceae (subgroup 4), Gemmatimonadaceae, Nitrosomonadaceae and the carbon metabolism of polymers. These results suggest that the continual returning of biochar increased soil nutrients, change bacterial community composition, and promoted the metabolic activity of polymer carbon sources in the drip-irrigated cotton field.


Assuntos
Bactérias/metabolismo , Carvão Vegetal , Microbiologia do Solo , Irrigação Agrícola , Bactérias/classificação , Fertilizantes , Gossypium/crescimento & desenvolvimento
10.
Cell Mol Neurobiol ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31808009

RESUMO

Aneurysmal subarachnoid hemorrhage (SAH) is an acute cerebrovascular emergency resulting from the rupture of a brain aneurysm. Despite only accounting for 5% of all strokes, SAH imposes a significant health burden on society due to its relatively young age at onset. Those who survive the initial bleed are often afflicted with severe disabilities thought to result from delayed cerebral ischemia (DCI). Consequently, elucidating the underlying mechanistic pathways implicated in DCI development following SAH remains a priority. Neuroinflammation has recently been implicated as a promising new theory for the development of SAH complications. However, despite this interest, clinical trials have failed to provide consistent evidence for the use of anti-inflammatory agents in SAH patients. This may be explained by the complexity of SAH as a plethora of inflammatory pathways have been shown to be activated in the disease. By determining how these pathways may overlap and interact, we hope to better understand the developmental processes of SAH complications and how to prevent them. The goal of this review is to provide insight into the available evidence regarding the molecular pathways involved in the development of inflammation following SAH and how SAH complications may arise as a result of these inflammatory pathways.

11.
PLoS One ; 14(12): e0226776, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31869397

RESUMO

Soil salinity is a major abiotic stress factor that limits cotton production worldwide. To improve salt tolerance in cotton, an in-depth understanding of ionic balance is needed. In this study, a pot experiment using three levels of soil salinity (0%, 0.2%, and 0.4%, represented as CK, SL, and SH, respectively) and two cotton genotypes (salt-tolerant genotype: L24; salt-sensitive genotype: X45) was employed to investigate how sodium chloride (NaCl) stress effects cotton growth, ion distribution, and transport, as well as to explore the related mechanism. The results showed that SL treatment mainly inhibited shoot growth, while SH treatment caused more extensive impairment to roots and shoots. The growth inhibition ratio of NaCl stress on X45 was more marked than that of L24. Under NaCl stress, the Na concentration in the roots, stems and leaves significantly increased, whereas the K, Cu, B, and Mo concentration in roots, as well as Mg and S concentrations in the leaves, significantly decreased. Under salt stress conditions, salt-tolerant cotton plants can store Na in the leaves, and as a result, a larger amount of minerals (e.g., Cu, Mo, Si, P, and B) tend to transport to the leaves. By contrast, salt-sensitive varieties tend to accumulate certain minerals (e.g., Ca, P, Mg, S, Mn, Fe, Cu, B, Mo, and Si) in the roots. Most genes related to ion transport and homeostasis were upregulated in L24, but not in X45. The expression level of GhSOS1 in X45 was higher than L24, but GhNHX1 in L24 was higher than X45. Our findings suggest that the two varieties response to salt stress differently; for X45 (salt-sensitive), the response is predominantly governed by Na+ efflux, whereas for L24 (salt-tolerant), vacuolar sequestration of Na+ is the major mechanism. The expression changes of the genes encoding the ion transporters may partially explain the genotypic difference in leaf ion accumulation under salt stress conditions.

12.
World Neurosurg ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31756500

RESUMO

OBJECTIVE: Ventriculostomy-related infection (VRI) is associated with potential serious morbidity, extended hospitalization duration, increased health care costs, and mortality. We assessed the effectiveness of a pragmatic risk-stratification pathway for external ventricular drain (EVD) management, allowing for surgical decision making, in reducing the rate of VRIs. METHODS: Two studies were performed concurrently. A retrospective audit of EVD infection rates and outcomes in our unit across 3 hospitals was conducted from January to December 2014. The second prospective study compared the same variables during the implementation of the EVD pathway across the 3 sites from January 2015 to December 2016. RESULTS: The number of patients requiring EVDs increased from 2014 to 2016 (165 vs. 189 vs. 197 patients, respectively), with a significant increase in patients with intraventricular hemorrhage (P = 0.009). Despite increasing risk, overall EVD infections decreased during the implementation period, from 4.8% (8/165) in 2014 to 3.7% in 2015 (7/189) and 2.0% in 2016 (4/197, P = 0.33). In 2 sites (site 1, 2.0% vs. 2.1% vs. 1.9%, and site 2, 4.7% vs. 5.0% vs. 5.3%), transition to the EVD risk-stratification pathway maintained already low infection rates; in site 3, EVD infections decreased from 6.8% (5/73) to 3.9% (4/102) and 0% (0/86, P = 0.06). CONCLUSIONS: The introduction of a pragmatic evidence-based risk-stratification pathway, in which different options for EVD management are incorporated, results in low EVD infection rates across a multisite institutional practice. Our results are comparable to published protocols involving the implementation of standard care bundles and/or antibacterial EVDs alone, in reducing VRIs.

13.
Onco Targets Ther ; 12: 7573-7580, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571908

RESUMO

Purpose: Colorectal cancer (CRC) is the most common malignancy in the gastrointestinal tract. The liver is the most common location of CRC metastases, which are the main causes of CRC-related death. However, the mechanisms underlying metastasis of CRC to the liver have not been characterized, resulting in therapeutic challenges. Methods: The effects of hepatic stellate cells (HSCs) on T cells were evaluated using in vitro mixed lymphocyte reactions (MLRs) and cytokine production assays. HSC-induced CT26 cell migration and proliferation were evaluated in vitro and in vivo. Results: HSCs induced T cell hypo-responsiveness, promoted T cell apoptosis, and induced regulatory T cell expansion in vitro. IL-2 and IL-4 were significantly lower in MLRs incubated with HSCs. Supernatants of MLRs with HSCs promoted CT26 cell proliferation and migration. Furthermore, the presence of HSCs increased the number of liver metastases and promoted proliferation of liver metastatic tumor cells in vivo. Conclusion: HSCs may contribute to an immunosuppressive liver microenvironment, resulting in a favorable environment for the colonization of CRC cells in the liver. These findings highlight a potential strategy for treatment of CRC liver metastases.

14.
Nat Commun ; 10(1): 4764, 2019 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-31628307

RESUMO

Water is arguably the most common and yet least understood material on Earth. Indeed, the biophysical behavior of water in crowded intracellular milieu is a long-debated issue. Understanding of the spatial and compositional heterogeneity of water inside cells remains elusive, largely due to a lack of proper water-sensing tools with high sensitivity and spatial resolution. Recently, stimulated Raman excited fluorescence (SREF) microscopy was reported as the most sensitive vibrational imaging in the optical far field. Herein we develop SREF into a water-sensing tool by coupling it with vibrational solvatochromism. This technique allows us to directly visualize spatially-resolved distribution of water states inside single mammalian cells. Qualitatively, our result supports the concept of biological water and reveals intracellular water heterogeneity between nucleus and cytoplasm. Quantitatively, we unveil a compositional map of the water pool inside living cells. Hence we hope SREF will be a promising tool to study intracellular water and its relationship with cellular activities.


Assuntos
Microscopia de Fluorescência/métodos , Microscopia Óptica não Linear/métodos , Análise de Célula Única/métodos , Água/metabolismo , Núcleo Celular/química , Núcleo Celular/metabolismo , Fenômenos Fisiológicos Celulares , Cor , Citoplasma/química , Citoplasma/metabolismo , Células HeLa , Humanos , Espaço Intracelular/química , Espaço Intracelular/metabolismo , Reprodutibilidade dos Testes , Solventes/química , Vibração , Água/química
15.
J Cancer ; 10(20): 4947-4953, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31598167

RESUMO

Radiotherapy for liver cancer can affect the level of autophagy in cells, and effective autophagy regulation can increase the radiosensitivity of liver cancer cells.Saikosaponin-d (SSd) is an effective active ingredient extracted from traditional Chinese medicine Bupleurum. We have confirmed previously in vitro and in vitro experiments that SSd can significantly induce apoptosis of liver cancer cells, increase the radiosensitivity of liver cancer cells.This study explored the role of autophagy in SSd-mediated radiosensitivity of liver cancer cells. MTT and clone formation experiments showed that radiation can inhibit the proliferation of hepatoma cells and reduce the colony formation of hepatoma cells. After the addition of SSd, the inhibitory effect of radiation on the proliferation and clonal formation of hepatoma cells was further enhanced. However, the addition of the autophagy inhibitor chloroquine or mTOR agonist can partially reverse the inhibitory effect of the combined treatment of SSd with radiation on the proliferation of hepatoma cells. Similarly, transmission electron microscopy and laser confocal microscopy showed that after the addition of SSd, the number of radiation-induced autophagosomes increased significantly in hepatoma cells and the intervention of mTOR agonist can reduce the formation of autophagosomes in hepatoma cells.In addition,Western blot analysis presented that radiation significantly increased LC3-II levels. Especially when SSd is added, LC3-II levels is further increased. Our data indicate that SSd can inhibit the growth of liver cancer cells and enhance cell radiosensitivity by inducing autophagy formation.

16.
Nat Methods ; 16(9): 830-842, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31471618

RESUMO

All molecules consist of chemical bonds, and much can be learned from mapping the spatiotemporal dynamics of these bonds. Since its invention a decade ago, stimulated Raman scattering (SRS) microscopy has become a powerful modality for imaging chemical bonds with high sensitivity, resolution, speed and specificity. We introduce the fundamentals of SRS microscopy and review innovations in SRS microscopes and imaging probes. We highlight examples of exciting biological applications, and share our vision for potential future breakthroughs for this technology.


Assuntos
Substâncias Macromoleculares/análise , Imagem Molecular/métodos , Microscopia Óptica não Linear/métodos , Animais , Humanos
17.
Chem Commun (Camb) ; 55(63): 9379-9382, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31317975

RESUMO

Small-molecule natural products have been an essential source of pharmaceuticals to treat human diseases, but very little is known about their behavior inside dynamic, live human cells. Here, we demonstrate the first structure-activity-distribution relationship (SADR) study of complex natural products, the anti-cancer antimycin-type depsipeptides, using the emerging bioorthogonal Stimulated Raman Scattering (SRS) Microscopy. Our results show that the intracellular enrichment and distribution of these compounds are driven by their potency and specific protein targets, as well as the lipophilic nature of compounds.


Assuntos
Antimicina A/análogos & derivados , Antineoplásicos/química , Depsipeptídeos/química , Antimicina A/química , Antimicina A/metabolismo , Antimicina A/farmacologia , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Depsipeptídeos/metabolismo , Depsipeptídeos/farmacologia , Células HeLa , Humanos , Células MCF-7 , Microscopia de Fluorescência , Análise Espectral Raman , Relação Estrutura-Atividade
18.
J Phys Chem Lett ; 10(13): 3563-3570, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31185166

RESUMO

Fluorescence spectroscopy and Raman spectroscopy are two major classes of spectroscopy methods in physical chemistry. Very recently, stimulated Raman excited fluorescence (SREF) has been demonstrated ( Xiong, H.; et al. Nature Photonics , 2019 , 13 , 412 - 417 ) as a new hybrid spectroscopy that combines the vibrational specificity of Raman spectroscopy with the superb sensitivity of fluorescence spectroscopy (down to the single-molecule level). However, this proof-of-concept study was limited by both the tunability of the commercial laser source and the availability of the excitable molecules in the near-infrared. As a result, the generality of SREF spectroscopy remains unaddressed, and the understanding of the critical electronic preresonance condition is lacking. In this work, we built a modified excitation source to explore SREF spectroscopy in the visible region. Harnessing a large palette of red dyes, we have systematically studied SREF spectroscopy on a dozen different cases with a fine spectral interval of several nanometers. The results not only establish the generality of SREF spectroscopy for a wide range of molecules but also reveal a tight window of proper electronic preresonance for the stimulated Raman pumping process. Our theoretical modeling and further experiments on newly synthesized dyes also support the obtained insights, which would be valuable in designing and optimizing future SREF experiments for single-molecule vibrational spectroscopy and supermultiplex vibrational imaging.

19.
Nat Biomed Eng ; 3(5): 402-413, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31036888

RESUMO

Cells and tissues often display pronounced spatial and dynamical metabolic heterogeneity. Common glucose-imaging techniques report glucose uptake or catabolism activity, yet do not trace the functional utilization of glucose-derived anabolic products. Here we report a microscopy technique for the optical imaging, via the spectral tracing of deuterium (STRIDE), of diverse macromolecules derived from glucose. Based on stimulated Raman-scattering imaging, STRIDE visualizes the metabolic dynamics of newly synthesized macromolecules, such as DNA, protein, lipids and glycogen, via the enrichment and distinct spectra of carbon-deuterium bonds transferred from the deuterated glucose precursor. STRIDE can also use spectral differences derived from different glucose isotopologues to visualize temporally separated glucose populations using a pulse-chase protocol. We also show that STRIDE can be used to image glucose metabolism in many mouse tissues, including tumours, brain, intestine and liver, at a detection limit of 10 mM of carbon-deuterium bonds. STRIDE provides a high-resolution and chemically informative assessment of glucose anabolic utilization.


Assuntos
Deutério/química , Glucose/metabolismo , Imagem Óptica/métodos , Animais , Animais Recém-Nascidos , Linhagem Celular Tumoral , Humanos , Intestinos , Lipídeos/biossíntese , Substâncias Macromoleculares/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Nus , Biossíntese de Proteínas , Análise Espectral Raman
20.
Cancer Lett ; 453: 158-169, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30954649

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with no effective treatment. Cancer cells, especially cancer stem cells (CSCs), redirect immune cells to evade immune surveillance and even coopt these immune cells to support their growth and metastasis. However, the identification of CSCs and how CSCs interact with immune cells in PDAC remain uncharacterized. Here, we report that CD90 is expressed on both stromal and tumor cells and that high expression of CD90 is related to a poor prognosis in patients with PDAC. The CD90 highly expressed (CD90hi) population in PDAC cells harbors high stemness features and tumorigenicity. Notably, CD90 acts as an anchor for monocyte/macrophage adhesion, providing a physical interaction between CD90hi cells and monocytes/macrophages. In response, the crosstalk between CD90hi cells and monocytes/macrophages promotes immunosuppressive features of immune cells, which enhance the stemness and epithelial-mesenchymal transition (EMT) of PDAC cells. Moreover, PD-L1 is dominantly expressed in the CD90hi population, providing another strategy for these cells to evade immune surveillance. These findings provide an understanding of the biological significance of CD90 expression in PDAC cells and uncover a novel mechanism for how "stem-like" PDAC cells evade immune surveillance.

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