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1.
J Alzheimers Dis ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34602486

RESUMO

BACKGROUND: Amyloid plaques and neurofibrillary tangles are two pathological hallmarks of Alzheimer's disease (AD). However, synaptic deficits occur much earlier and correlate stronger with cognitive decline than amyloid plaques and neurofibrillary tangles. Mislocalization of tau is an early hallmark of neurodegeneration and precedes aggregations. Sirtuin type 1 (SIRT1) is a deacetylase which acts on proteins including transcriptional factors and associates closely with AD. OBJECTIVE: The present study investigated the association between SIRT1 and tau expression in cells and in mice brains. METHODS: Western blot was performed to detected tau, SIRT1, C/EBPα, and GAPDH protein levels. Immunological fluorescence assay was used to assess tau localization in primary cortical neuronal cells. Golgi staining was performed to evaluated dendritic spine morphology in mice brains. RESULTS: In the present study, we found that SIRT1 negatively regulates expression of tau at the transcriptional level through transcriptional factor C/EBPα. Inhibition of the activity of SIRT1 limits the distribution of tau to the neurites. In the meantime, the alteration of dendritic spine morphology is also observed in the brains of SIRT1+/- mice. CONCLUSION: SIRT1 may be a potential drug target for early intervention in AD.

3.
Geroscience ; 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34480713

RESUMO

It has been demonstrated that elamipretide (SS-31) rescues age-related functional deficits in the heart but the full set of mechanisms behind this have yet to be determined. We investigated the hypothesis that elamipretide influences post-translational modifications to heart proteins. The S-glutathionylation and phosphorylation proteomes of mouse hearts were analyzed using shotgun proteomics to assess the effects of aging on these post-translational modifications and the ability of the mitochondria-targeted drug elamipretide to reverse age-related changes. Aging led to an increase in oxidation of protein thiols demonstrated by increased S-glutathionylation of cysteine residues on proteins from Old (24 months old at the start of the study) mouse hearts compared to Young (5-6 months old). This shift in the oxidation state of the proteome was almost completely reversed by 8 weeks of treatment with elamipretide. Many of the significant changes that occurred were in proteins involved in mitochondrial or cardiac function. We also found changes in the mouse heart phosphoproteome that were associated with age, some of which were partially restored with elamipretide treatment. Parallel reaction monitoring of a subset of phosphorylation sites revealed that the unmodified peptide reporting for Myot S231 increased with age, but not its phosphorylated form and that both phosphorylated and unphosphorylated forms of the peptide covering cMyBP-C S307 increased, but that elamipretide treatment did not affect these changes. These results suggest that changes to thiol redox state and phosphorylation status are two ways in which age may affect mouse heart function, which can be restored by treatment with elamipretide.

4.
J Xray Sci Technol ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34511478

RESUMO

OBJECTIVE: To compare and evaluate diagnostic capabilities of preoperative ultrasonography (US) and magnetic resonance imaging (MRI) in the cervical lymph nodes of patients with papillary thyroid cancer. METHODS: A retrospective dataset involving 156 patients who had undergone thyroidectomy and preoperative US and MRI was assembled. Among these, 69 had cervical lymph node metastasis and 87 did not. At least four radiologists unilaterally and spontaneously investigated the US and MRI attributes of the cervical lymph nodes. The efficiency of diagnostic imaging for cervical lymph nodes, including their true-positive rate or sensitivity, true-negative rate or specificity, positive predictive value, negative predictive value, and predictive accuracy were analysed and assessed. RESULTS: In the assessment of cervical lymph node metastases of papillary thyroid cancer, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of diagnostic US vs. MRI were 58.0% vs. 79.7%, 69.0% vs. 83.9%, 59.7% vs. 79.7%, 67.4% vs. 83.9%, and 64.1% vs. 82.1%, respectively. The accuracy consistency of the two imaging modalities was 83.5%. CONCLUSIONS: MRI is more effective than US in diagnosing and assessing cervical lymph node metastases of papillary thyroid cancer.

5.
Adv Sci (Weinh) ; : e2102730, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34495577

RESUMO

Perovskite materials in different dimensions show great potential in direct X-ray detection, but each with limitations stemming from its own intrinsic properties. Particularly, the sensitivity of two-dimensional (2D) perovskites is limited by poor carrier transport while ion migration in three-dimensional (3D) perovskites causes the baseline drifting problem. To circumvent these limitations, herein a double-layer perovskite film is developed with properly aligned energy level, where 2D (PEA)2 MA3 Pb4 I13 (PEA=2-phenylethylammonium, MA=methylammonium) is cascaded with vertically crystallized 3D MAPbI3 . In this new design paradigm, the 3D layer ensures fast carrier transport while the 2D layer mitigates ion migration, thus offering a high sensitivity and a greatly stabilized baseline. Besides, the 2D layer increases the film resistivity and enlarges the energy barrier for hole injection without compromising carrier extraction. Consequently, the double-layer perovskite detector delivers a high sensitivity (1.95 × 104 µC Gyair -1 cm-2 ) and a low detection limit (480 nGyair s-1 ). Also demonstrated is the X-ray imaging capacity using a circuit board as the object. This work opens up a new avenue for enhancing X-ray detection performance via cascade assembly of various perovskites with complementary properties.

6.
NanoImpact ; 232021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34514184

RESUMO

Carbon dots (CDs) are a promising material currently being explored in many industrial applications in the biomedical and agri-food areas; however, studies supporting the environmental health risk assessment of CDs are needed. This study focuses on various CD forms including iron (FeCD) and copper (CuCD) doped CDs synthesized using hydrothermal method, their fate in gastrointestinal tract, and their cytotoxicity and potential changes to cellular metabolome in a triculture small intestinal epithelial model. Physicochemical characterization revealed that 75% of Fe in FeCD and 95% of Cu in CuCD were dissolved during digestion. No significant toxic effects were observed for pristine CDs and FeCDs. However, CuCD induced significant dose-dependent toxic effects including decreases in TEER and cell viability, increases in cytotoxicity and ROS production, and alterations in important metabolites, including D-glucose, L-cysteine, uridine, citric acid and multiple fatty acids. These results support the current understanding that pristine CDs are relatively non-toxic and the cytotoxicity is dependent on the doping molecules.

8.
J Hazard Mater ; 416: 125930, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492860

RESUMO

The pollution of heavy metals and organic compounds has received increased attention in recent years. In the current study, a novel biochar-based iron oxide composite (FeYBC) was successfully synthesized using pomelo peel and ferric chloride solution through one-step process at moderate temperature. Results clearly demonstrate that FeYBC exhibited more efficient removal of Cr(VI) and/or phenol compared with the pristine biochar, and the maximum adsorption amounts of Cr(VI) and phenol by FeYBC could reach 24.37 and 39.32 mg g-1, respectively. A series of characterization data suggests that several iron oxides such as Fe2O3, Fe0, FeOOH and Fe3O4 were formed on the FeYBC surface as well as oxygen-containing groups. Thermodynamics study indicates that Cr(VI) and phenol adsorption by FeYBC were endothermic and exothermic processes, respectively. Langmuir adsorption isotherm and pseudo-second order models could better explain the Cr(VI) and phenol adsorption behaviors over FeYBC. The Cr(VI) adsorption might be primarily achieved through the ion exchange and surface complexation and reduction, whereas the π-π interaction and electron donor-acceptor complex mainly contributed to phenol adsorption. The findings indicate that the biochar-based iron oxide composites material was an efficient adsorbent for the remediation of industrial effluents containing Cr(VI) and phenol.


Assuntos
Poluentes Químicos da Água , Água , Adsorção , Carvão Vegetal , Cromo , Compostos Férricos , Cinética , Fenol , Poluentes Químicos da Água/análise
9.
Brain Imaging Behav ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34549378

RESUMO

Neuroimaging studies have displayed aberrant brain activities in individual sensory- and emotional-linked regions in postherpetic neuralgia (PHN) patients. However, multi-dimensional dysfunction in chronic pain may rely on the interplay between networks. Little is known about the changes in the functional architecture of resting state networks (RSNs) in PHN. In this cross-sectional study, we recruited 31 PHN patients, 33 RHZ patients and 34 HCs; all participants underwent resting-state functional magnetic resonance imaging scans. We investigated the differences of within- and cross-network connectivities between different outcomes of HZ patients [including PHN and recuperation from herpes zoster (RHZ)] and healthy controls (HCs) so as to extract a characteristic network pattern of PHN. The abnormal network connectivities were then correlated with clinical variables in respective groups. PHN and RHZ patients could be similarly characterized by abnormal within-default mode network (DMN), DMN-salience network (SN) and SN-basal ganglia network (BGN) connectivity relative to HCs. Of note, compared with RHZ patients, PHN patients could be characterized by abnormal DMN-BGN and within-BGN connectivity. Furthermore, the within-DMN connectivity was associated with pain-induced emotional scores among PHN patients. Our study presented that network-level imbalance could account for the pain-related dysfunctions in different outcomes of herpes zoster patients. These insights are potentially useful for understanding neuromechanism of PHN and providing central therapeutic targets for PHN.

10.
Med Sci Monit ; 27: e933084, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34471085

RESUMO

The abnormal accumulation of amyloid-b (Ab) and neurofibrillary tangles (NFTs) containing phosphorylated tau proteins are the main histopathological feature of Alzheimer's disease (AD). Synaptic damage and loss are earlier events than amyloid plaques and NFTs in AD progress and best correlate with cognitive deficits in AD patients. Soluble oligomeric Aß initiates the progression of AD and tau mediates the subsequent synaptic impairments at an early stage of AD. In this review we discuss how Ab or/and tau causes synaptic dysfunction. Ab oligomers gather at synapses and give rise to synaptic death in a variety of ways such as regulating receptors and receptor tyrosine kinases, unbalancing calcium homeostasis, and activating caspases and calcineurin. A large amount of hyperphosphorylated tau exists in the synapse of the AD brain. Aß-triggered synaptic deficits are dependent on tau. Soluble, hyperphosphorylated tau is much more correlated to cognitive decline in AD patients. Tau-targeted therapies have received more attention because the treatments targeting Aß failed in AD. Here, we also review the therapy strategies used to intervene in the very early stages of AD. Soluble hyperphosphorylated tau forms a complex with cell surface receptors, scaffold proteins, or intracellular signaling molecules to damage synaptic function. Therefore, therapeutic strategies targeting synaptic tau at the early stage of AD may ameliorating pathology in AD. This review aims to provide an update on the role of oligomeric Ab and soluble hyperphosphorylated tau in the early pathogenesis of Alzheimer's disease and to develop a new treatment strategy based on this.

11.
Cell Death Dis ; 12(10): 883, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580275

RESUMO

Protein phosphatase 6 (PP6) is a member of the PP2A-like subfamily, which plays significant roles in numerous fundamental biological activities. We found that PPP6C plays important roles in male germ cells recently. Spermatogenesis is supported by the Sertoli cells in the seminiferous epithelium. In this study, we crossed Ppp6cF/F mice with AMH-Cre mice to gain mutant mice with specific depletion of the Ppp6c gene in the Sertoli cells. We discovered that the PPP6C cKO male mice were absolutely infertile and germ cells were largely lost during spermatogenesis. By combing phosphoproteome with bioinformatics analysis, we showed that the phosphorylation status of ß-catenin at S552 (a marker of adherens junctions) was significantly upregulated in mutant mice. Abnormal ß-catenin accumulation resulted in impaired testicular junction integrity, thus led to abnormal structure and functions of BTB. Taken together, our study reveals a novel function for PPP6C in male germ cell survival and differentiation by regulating the cell-cell communication through dephosphorylating ß-catenin at S552.

12.
Methods Enzymol ; 657: 443-480, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34353498

RESUMO

Near-infrared (NIR) targeting contrast agents have been investigated as great photoabsorbers to improve photoacoustic microscopy (PAM), OCT, and fluorescence imaging contrast for visualization of various diseases. In ophthalmology, a limited number of NIR contrast agents have been approved for clinical use. Recently, gold nanoparticles with different size and shapes have been developed for molecular imaging. This chapter provides the principles of multimodality PAM, OCT, and fluorescence imaging as well as a brief overview of contrast agents for optical imaging. A detailed protocol for the fabrication of discrete colloidal gold nanoparticles (GNPs), synthesis of functionalized RGD-conjugated chain-like GNP (CGNP) clusters labeled with indocyanine green (ICG) fluorescence dye (ICG@CGNP clusters-RGD), and validation of the synthesized nanoparticles to evaluate newly developed blood vessels in the retina, named choroidal neovascularization (CNV), is described. Using RGD peptide, ICG@CGNPs clusters-RGD can bind integrin which is expressed on activated endothelial cells and newly developed CNV. The targeting efficiency of nanoparticles is monitored by multimodality PAM, OCT, and fluorescence imaging longitudinally.


Assuntos
Nanopartículas Metálicas , Tomografia de Coerência Óptica , Meios de Contraste , Células Endoteliais , Ouro , Microscopia de Fluorescência , Retina
13.
Aging (Albany NY) ; 13(15): 19375-19396, 2021 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-34390328

RESUMO

BACKGROUND: BM-MSCs contribute to Helicobacter pylori (H. pylori)-induced gastric cancer, but their mechanism is still unclear. The aim of our study was to investigate the specific role and mechanism of BM-MSCs in H. pylori-induced gastric cancer. MAIN METHODS: Mice received total bone marrow transplants and were then infected with H. pylori. BM-MSCs were extracted and transplanted into the gastric serosal layer of mice chronically infected with H. pylori. Hematoxylin and eosin staining, immunohistochemistry staining and immunofluorescence were performed to detect tumor growth and angiogenesis in mouse stomach tissues. Chicken chorioallantoic membrane assays, xenograft tumor models, and human umbilical vein endothelial cell tube formation assays were used for in vivo and in vitro angiogenesis studies. THBS4 was screened from RNA-seq analysis of gastric tissues of BM-MSCs transplanted into H. pylori-infected mice. RESULTS: BM-MSCs can migrate to the site of chronic mucosal injury and promote tumor angiogenesis associated with chronic H. pylori infection. Migration of BM-MSCs to the site of chronic mucosal injury induced the upregulation of THBS4, which was also evident in human gastric cancer and correlated with increased blood vessel formation and worse outcome. The THBS4/integrin α2 axis promoted angiogenesis by facilitating the PI3K/AKT pathway in endothelial cells. CONCLUSIONS: Our results revealed a novel proangiogenic effect of BM-MSCs in the chronic H. pylori infection microenvironment, primarily mediated by the THBS4/integrin α2 axis, which activates the PI3K/AKT pathway in endothelial cells and eventually induces the formation of new tumor vessels.

14.
Trop Med Infect Dis ; 6(3)2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34449729

RESUMO

Ross River virus (RRV), the most common human arbovirus infection in Australia, causes significant morbidity and substantial medical costs. About half of Australian cases occur in Queensland. We describe the spatial and temporal patterns of RRV disease in Queensland over the past two decades. RRV notifications, human population data, and weather data from 2001 to 2020 were analysed by the Statistical Area Level 2 (SA2) area. Spatial interpolation or linear extrapolation were used for missing weather values and the estimated population in 2020, respectively. Notifications and incidence rates were analysed through space and time. During the study period, there were 43,699 notifications in Queensland. The highest annual number of notifications was recorded in 2015 (6182), followed by 2020 (3160). The average annual incidence rate was 5 per 10,000 people and the peak period for RRV notifications was March to May. Generally, SA2 areas in northern Queensland had higher numbers of notifications and higher incidence rates than SA2 areas in southern Queensland. The SA2 areas with high incidence rates were in east coastal areas and western Queensland. The timely prediction may aid disease prevention and routine vector control programs, and RRV management plans are important for these areas.

15.
Food Res Int ; 147: 110449, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34399451

RESUMO

Mud cellars have long been used as anaerobic bioreactors for the fermentation of Chinese strong-flavor Baijiu, where starchy raw materials (mainly sorghum) are metabolized to ethanol and various flavor compounds by multi-species microorganisms. Jiupei (fermented grains) and pit mud are two spatially linked microbial habitats in the mud cellar, yet their metabolic division of labor remains unclear. Here, we investigated the changes in environmental variables (e.g., temperature, oxygen, pH), key metabolites (e.g., ethanol, organic acids) and microbial communities in jiupei and pit mud during fermentation. Jiupei (low pH, high ethanol) and pit mud (neutral pH) provided two habitats with distinctly different environmental conditions for microbial growth. Lactic acid accumulated in jiupei, while butyric and hexanoic acids were mainly produced by microbes inhabiting the pit mud. Biomass analysis using quantitative real-time PCR showed that bacteria dominated the microbial consortia during fermentation, moreover cluster and principal coordinate analysis (PCoA) analysis showed that the bacterial communities of jiupei and pit mud were significantly divergent. The bacterial community diversity of jiupei decreased significantly during the fermentation process, and was relatively stable in pit mud. Lactobacillus dominated the jiupei bacterial community, and its relative abundance reached 98.0% at the end of fermentation. Clostridia (relative abundance: 42.9-85.5%) was the most abundant bacteria in pit mud, mainly distributed in the genus Hydrogenispora (5.3-68.4%). Fungal communities of jiupei and pit mud showed a similar succession pattern, and Kazachstania, Aspergillus and Thermoascus were the predominant genera. PICRUSt analysis demonstrated that enzymes participating in the biosynthesis of acetic and lactic acid were mainly enriched in jiupei samples, while the bacterial community in the pit mud displayed greater potential for butyric and hexanoic acid synthesis. Assays from an in vitro simulated fermentation further validated the roles of jiupei microbiota in acetic and lactic acid production, and these acids were subsequently metabolized to butyric and hexanoic acid by the pit mud microbiota. This work has demonstrated the synergistic cooperation between the microbial communities of jiupei and pit mud for the representative flavor formation of strong-flavor Baijiu.


Assuntos
Consórcios Microbianos , Microbiota , Bebidas Alcoólicas/análise , Bactérias/genética , Fermentação
16.
J Proteome Res ; 20(9): 4452-4461, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34351778

RESUMO

Recent advances in sample preparation enable label-free mass spectrometry (MS)-based proteome profiling of small numbers of mammalian cells. However, specific devices are often required to downscale sample processing volume from the standard 50-200 µL to sub-µL for effective nanoproteomics, which greatly impedes the implementation of current nanoproteomics methods by the proteomics research community. Herein, we report a facile one-pot nanoproteomics method termed SOPs-MS (surfactant-assisted one-pot sample processing at the standard volume coupled with MS) for convenient robust proteome profiling of 50-1000 mammalian cells. Building upon our recent development of SOPs-MS for label-free single-cell proteomics at a low µL volume, we have systematically evaluated its processing volume at 10-200 µL using 100 human cells. The processing volume of 50 µL that is in the range of volume for standard proteomics sample preparation has been selected for easy sample handling with a benchtop micropipette. SOPs-MS allows for reliable label-free quantification of ∼1200-2700 protein groups from 50 to 1000 MCF10A cells. When applied to small subpopulations of mouse colon crypt cells, SOPs-MS has revealed protein signatures between distinct subpopulation cells with identification of ∼1500-2500 protein groups for each subpopulation. SOPs-MS may pave the way for routine deep proteome profiling of small numbers of cells and low-input samples.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34455563

RESUMO

Spatial and temporal variations in soil denitrification and anaerobic ammonium oxidation (anammox) across the freshwater-oligohaline wetlands in subtropical estuary have not been well understood. In this study, continuous-flow soil core incubation combined with nitrogen isotope tracer was used to determine denitrification and anammox rates across freshwater-oligohaline tidal wetlands in Min River Estuary, Southeast China. Areal rates of denitrification and anammox varied from 3.89 to 19.0 µmol m-2 h-1 and from 0.15 to 1.11 µmol m-2 h-1, respectively, across these wetlands and throughout sampling months. Denitrification rates were higher in warm months (July, September) than in cool months (November, January), whereas anammox did not vary significantly across the sampling months. Average denitrification rates throughout the sampling months were higher in freshwater than in oligohaline wetlands, while anammox rates did not vary among the wetlands. Relative contribution of anammox (Ra) to N2 production (including denitrification and anammox) varied from 1.03 to 18.3% across the sampling months and wetlands. Denitrification rates differed significantly across the wetlands and sampling months. Anammox rates and Ra did not vary significantly among the sampling months. Denitrification rates were positively correlated with water content, total organic carbon (TOC), total nitrogen, dissolved organic nitrogen, NH4+, NOx-, Fe2+, and Fe2+/Fe3+, but negatively related to pH. Anammox rates showed negative relationships with water content and TOC. Water content, temperature, and pH were crucial for organic carbon and Fe2+ availability with important implications on denitrification and anammox. Therefore, denitrification rates vary significantly, whereas anammox rates do not vary significantly across freshwater-oligohaline wetlands in the Min River Estuary.

18.
Water Res ; 203: 117515, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34388498

RESUMO

Dissolved organic carbon derived from biomass-pyrogenic smoke (SDOC) can be transported and deposited with atmospheric aerosols, enter aqueous environments, and possibly alter aqueous chemistry and quality. However, the characteristics of SDOC in aqueous environments and their effects on the fate of hydrophobic organic pollutants are poorly understood. In this study, we found that the emitted SDOC is 7.2∼19.6 wt.% of biochar retained in situ after biomass pyrolysis, and the emitted SDOC is approximately 1-3 orders of magnitude greater than dissolved organic carbon (DOC) released from biochar in a short term, which indicates that SDOC is a more important source of DOC in aqueous environments relative to biochar-released DOC after a biomass burning/pyrolysis event. The characteristics of SDOC in aqueous environments are dominated by the <1000 Da fraction, which accounts for >96 wt.% of bulk SDOC. In comparison with DOC in biochar, natural water, and soil, the S275-295 value of SDOC (0.037-0.053) is significantly greater, further indicating that SDOC has a smaller molecular size. Moreover, fluorescence EEM suggests that a fluorescence component located at the Ex/Em of 205/310 nm and the combinational ranges of fluorescence index (1.28-2.28), humification index (0.07-0.80), and biological index (1.16-1.72) can be used to identify SDOC from DOC in other media. Solubilization experiments indicated that SDOC (20 mg/L) improved the solubility of hydrophobic pollutants (pyrene and triclocarban) by 2-6 folds in aqueous environments, which potentially enhances the mobility of pollutants and enlarges the potential risk region. This study indicates that SDOC may cause a severe harm to aqueous environments in addition to the atmosphere. The results have profound implications for comprehensive assessments of the environmental effects of SDOC while promoting its identification and elucidating its behavior in aqueous environments.


Assuntos
Carbono , Poluentes Ambientais , Biomassa , Fumaça , Água
19.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(4): 385-388, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34374258

RESUMO

Objective: To investigate the role of cell autophagy in lung ischemia/reperfusion injury in rats. Methods: Forty SD rats were randomly divided into 5 groups (n=8): ①Sham operated group (sham group):just open rat chest for 3.5 h; ②Ischemia/reperfusion group (I/R group):after open chest, clamp pulmonary hilus for 0.5h then reperfusion for 3 h; ③Solvent group (DMSO group): intraperitoneal injection of DMSO solution for 1h before operation; ④Autophagic inhibitor group (3-MA group); ⑤Autophagic agonist group (Rap group): intraperitoneal injection of autophagic agonist rapamycin before operation; the rest operations of DMSO, 3-MA and Rap groups are the same as that of I/R group. At the end of the experiment, the rats were killed by euthanasia-killing. The lung tissues were collected and the wet/dry weight ratio (W/D) and total lung water content (TLW) of the lung tissues were detected. The lung tissue structure and cell ultramicro morphology were observed by light microscopy and electron microscopy and the injuried alveolar rate(IAR) was calculated. The autophagy-related protein expressions were detected by Western blot. Results: Compared with sham group, the levels of W/D, TLW and IAR were increased, the expressions of autophagy related protein and p-AMPK, Beclin 1, LC3 II were also increased in other four groups, while the protein expressions of p-mTOR and p62 were decreased significantly (P< 0.05 or P<0.01). Under the light microscope, the other groups of lung tissue had edema and exudation in varying degrees, the structure of alveoli was disordered, the ultrastructural damage of cells was aggravated under the electron microscope, and autophagosome could be observed. Compared with DMSO group, the expressions of autophagy related protein, the levels of W/D, TLW and IAR in 3-MA group were decreased (P<0.05 or P<0.01), the edema of lung interstitial was lighter, and less cells were found in alveolar cavity. Ultrastructural damage was also lighter and with less autophagosome. Besides, there was no significant difference among I/R, DMSO and Rap groups (P>0.05). Conclusion: Autophagy can be activated during ischemia/reperfusion in rats to induce lung injury.


Assuntos
Lesão Pulmonar , Traumatismo por Reperfusão , Animais , Autofagia , Isquemia , Pulmão , Ratos , Ratos Sprague-Dawley
20.
ACS Nano ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34378374

RESUMO

Stem cell regenerative medicine therapies have emerged as promising treatments for currently incurable diseases. A remaining challenge for cell therapies is the ability to track the migration and distribution of the transplanted cells in a long-term, noninvasive manner in vivo to assess their efficacy. This study develops a noninvasive, and high spatial resolution photoacoustic microscopy (PAM) and optical coherence tomography (OCT) imaging system for in vivo tracking of subretinally injected progenitor human retinal pigment epithelium cells (ARPE-19) labeled with chainlike gold nanoparticle (CGNP) clusters in RPE damage. CGNP provided significant PAM, OCT, and fluorescence signals to selectively track the migration of ARPE-19 cells in living rabbit eyes for 3 months. PAM and OCT imaging allow accurate anatomical information to determine the exact retinal layer in which the transplanted ARPE-19 cells are located which was confirmed by histology. This presents an efficient and advanced technology to visualize fundamental biological processes of cell therapies in complex in vivo environments in real time.

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