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1.
Org Lett ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34643399

RESUMO

Ovalene's nitrogenated derivative with all zigzag edges and nitrogen atom doping at the periphery has been developed via one-step nitrogenation of formylbisanthene. Because of nitrogen incorporation, these molecules show greatly decreased highest occupied molecular orbital levels, enhanced intermolecular interactions, and a reversible acid response. Aza-ovalene also exhibits a diatropic ring current along the periphery. This work provides rare examples of all-zigzag-edged N-polycyclic aromatic hydrocarbons.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34637590

RESUMO

Engineering of cell plasma membrane using functional DNA is important for study and control of cellular behaviors. However, most efforts limit to apply artificial DNA interactions on external cell membrane due to the lack of suitable synthetic tools to engineer intracellular side, which impedes many applications in cell biology. Inspired by natural extracellular vesicle-cell fusion process, we introduce a fusogenic spherical nucleic acid construct to realize robust DNA functionalization on both external and internal cell surfaces via liposome fusion-based transport (LiFT), enabling applications including construction of heterotypic cell assembly for programmed signaling pathway and detection of intracellular metabolites. This approach can engineer cell membrane in a highly efficient and spatially-controlled manner, allowing for building anisotropic membrane structure with two orthogonal DNA functionalities.

3.
Anal Chem ; 93(40): 13734-13741, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34605236

RESUMO

Precisely detecting biomarkers in living systems holds tremendous promise for disease diagnosis and monitoring. Herein, we developed a covalent organic framework (COF)-based tricolor fluorescent nanoprobe for simultaneously imaging biomarkers with different spatial locations in living cells. Briefly, a TAMRA-labeled survivin mRNA antisense nucleotide and a Cy5-labeled transmembrane glycoprotein mucin 1 (MUC1) aptamer were adsorbed on a nanoscale fluorescent COF. To enhance the interactions between COF nanoparticles (NPs) and nucleic acid molecules, a freezing method was employed for improving the nucleic acid loading density and ensuring detection performance. The fluorescence signals of dyes on DNAs were first quenched by the COF NPs. Internalization and distribution of the nanoprobes can be real-time visualized by the autofluorescence of COF NPs. In living cells, recognition between MUC1 with MUC1 aptamers causes fluorescence signal recovery of Cy5, while hybridization between survivin mRNA and its antisense DNA induces the signal recovery of TAMRA. Therefore, this COF-based multicolor nanoprobe could be employed for visualizing MUC1 on the cell membrane and survivin mRNA in the cytoplasm. Cancer cell-specific diagnostic imaging and monitoring of the process of cancer cell exosomes infecting normal cells using the nanoprobe were achieved. This work not only offers a versatile nanoprobe for bioanalysis but also provides new insights for developing novel COF-based nanoprobes.

4.
J Dairy Sci ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34538488

RESUMO

Bovine mammary epithelial cells undergo an increase in metabolic rate, mitochondrial dysfunction, and oxidative stress after calving. Nuclear factor erythroid 2-related factor 2 (NFE2L2), a master regulator of cellular redox homeostasis, plays crucial roles in the regulation of mitochondrial function. The objective of this study was to investigate the role of NFE2L2 on mitochondrial function in bovine mammary epithelial cells under hyperlipidemic conditions. Three experiments were conducted as follows: (1) the immortalized bovine mammary epithelial cell line MAC-T was treated with various concentrations of free fatty acids (FFA; 0, 0.6, 1.2, or 2.4 mM) for 24 h to induce stress; (2) MAC-T cells were transfected with small interfering RNA targeting NFE2L2 (si-NFE2L2) and scrambled nontarget negative control (si-Control) for 48 h; and (3) MAC-T cells were pretreated with 10 µM sulforaphane (SFN), an activator of NFE2L2, for 24 h followed by treatment with 1.2 mM FFA for an additional 24 h. Results indicated that exogenous FFA challenge induced linear and quadratic increases in concentrations of mitochondrial reactive oxygen species (ROS). Compared with 0 mM FFA, mitochondrial membrane potential, mRNA abundance of oxidative phosphorylation complexes (CO I-V), protein abundance of nuclear respiratory factor 1 (NRF1), peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α), mitochondrial transcription factor A (TFAM), and NFE2L2 along with the contents of ATP, mitochondrial DNA (mtDNA), and total mitochondria were greater in the MAC-T challenged with 0.6 mM FFA group, but lower in the 1.2 and 2.4 mM FFA cultures. Knockdown of NFE2L2 via small interfering RNA led to greater mitochondrial ROS content and lower mitochondrial membrane potential along with contents of ATP, mtDNA, and total mitochondria. The SFN pretreatment upregulated protein abundance of NFE2L2 and attenuated the downregulation of NFE2L2 induced by FFA. Pretreatment with SFN attenuated the downregulation induced by FFA of PGC-1α, NRF1, and TFAM protein abundance along with contents of mtDNA and total mitochondria. Furthermore, SFN pretreatment attenuated the upregulation of mitochondrial ROS content, the downregulation of mitochondrial membrane potential, and the decreases in ATP, mtDNA, and mitochondrial content induced by FFA. Overall, data indicated that FFA inhibit NFE2L2, resulting in mitochondrial dysfunction and ROS production in bovine mammary epithelial cells. Thus, NFE2L2 may be a promising therapeutic target against metabolic challenge-driven mitochondrial dysfunction and oxidative stress in bovine mammary epithelial cells.

6.
Acta Pharmacol Sin ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34522005

RESUMO

Behavioral sensitization is a progressive increase in locomotor or stereotypic behaviours in response to drugs. It is believed to contribute to the reinforcing properties of drugs and to play an important role in relapse after cessation of drug abuse. However, the mechanism underlying this behaviour remains poorly understood. In this study, we showed that mTOR signaling was activated during the expression of behavioral sensitization to cocaine and that intraperitoneal or intra-nucleus accumbens (NAc) treatment with rapamycin, a specific mTOR inhibitor, attenuated cocaine-induced behavioural sensitization. Cocaine significantly modified brain lipid profiles in the NAc of cocaine-sensitized mice and markedly elevated the levels of phosphatidylinositol-4-monophosphates (PIPs), including PIP, PIP2, and PIP3. The behavioural effect of cocaine was attenuated by intra-NAc administration of LY294002, an AKT-specific inhibitor, suggesting that PIPs may contribute to mTOR activation in response to cocaine. An RNA-sequencing analysis of the downstream effectors of mTOR signalling revealed that cocaine significantly decreased the expression of SynDIG1, a known substrate of mTOR signalling, and decreased the surface expression of GluA2. In contrast, AAV-mediated SynDIG1 overexpression in NAc attenuated intracellular GluA2 internalization by promoting the SynDIG1-GluA2 interaction, thus maintaining GluA2 surface expression and repressing cocaine-induced behaviours. In conclusion, NAc SynDIG1 may play a negative regulatory role in cocaine-induced behavioural sensitization by regulating synaptic surface expression of GluA2.

7.
Environ Int ; 157: 106866, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34525388

RESUMO

The exposome overhauls conventional environmental health impact research paradigms and provides a novel methodological framework that comprehensively addresses the complex, highly dynamic interplays of exogenous exposures, endogenous exposures, and modifiable factors in humans. Holistic assessments of the adverse health effects and systematic elucidation of the mechanisms underlying environmental exposures are major scientific challenges with widespread societal implications. However, to date, few studies have comprehensively and simultaneously measured airborne pollutant exposures and explored the associated biomarkers in susceptible healthy elderly subjects, potentially resulting in the suboptimal assessment and management of health risks. To demonstrate the exposome paradigm, we describe the rationale and design of a comprehensive biomarker and biomonitoring panel study to systematically explore the association between individual airborne exposure and adverse health outcomes. We used a combination of personal monitoring for airborne pollutants, extensive human biomonitoring, advanced omics analysis, confounding information, and statistical methods. We established an exploratory panel study of Biomarkers of Air Pollutant Exposure in Chinese people aged 60-69 years (China BAPE), which included 76 healthy residents from a representative community in Jinan City, Shandong Province. During the period between September 2018 and January 2019, we conducted prospective longitudinal monitoring with a 3-day assessment every month. This project: (1) leveraged advanced tools for personal airborne exposure monitoring (external exposures); (2) comprehensively characterized biological samples for exogenous and endogenous compounds (e.g., targeted and untargeted monitoring) and multi-omics scale measurements to explore potential biomarkers and putative toxicity pathways; and (3) systematically evaluated the relationships between personal exposure to air pollutants, and novel biomarkers of exposures and effects using exposome-wide association study approaches. These findings will contribute to our understanding of the mechanisms underlying the adverse health impacts of air pollution exposures and identify potential adverse clinical outcomes that can facilitate the development of effective prevention and targeted intervention techniques.

8.
J BUON ; 26(4): 1432-1439, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34565001

RESUMO

PURPOSE: To explore the effect of dexmedetomidine combined with flurbiprofen axetil on postoperative analgesia and immune function in patients with lung cancer after radical operation. METHODS: 60 lung cancer patients undergoing open chest radical surgery were selected and randomly divided into D & F Group (dexmedetomidine combined with flurbiprofen axetil) and F Group (flurbiprofen axetil), with 30 cases in each group. Before induction of general anesthesia, Group F was administered intravenous flurbiprofen axetil, and in D & F group, dexmedetomidine and erfuorbiprofen axetil were injected. RESULTS: At T2 (intubation) and T3 (extubation), map and HR in D & F group were significantly lower than those in F group (p<0.05). The extubation quality score of D & F group was significantly lower than that of F group (p<0.05). At 6 h and 12 h after operation, visual analogue scale (VAS) score and Bruggrmann comfort scale (BCS) score of D & F group were significantly lower than that of F group (p<0.05). The dosage of sufentanil and the times of pressing analgesia pump in group D & F were significantly less than those in group F (p<0.05). NK cells, CD3 + T cells and CD4 + / CD8 + in the D & F group were significantly higher than those in F group at 12h, 24h, 48 h and 1 week after operation (p<0.05). CONCLUSIONS: Flurbiprofen axetil can improve postoperative pain, but combined with dexmedetomidine better effect, postoperative comfort and immune function of patients were significantly improved.

9.
Medicine (Baltimore) ; 100(38): e27321, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34559149

RESUMO

ABSTRACT: Stroke-associated pneumonia (SAP) is a spectrum of pulmonary infections in patients within 7 days of stroke. Which is one of the most common complications after stroke and is significantly associated with a poor prognosis of stroke. To the best of our knowledge, a bibliometric method was not previously used to analyze the topic of SAP; we aim to describe the situation and evolution of SAP from 2003 to 2020, and to discuss the research hotspots and frontiers.A total of 151 articles were retrieved from the Scopus database. Bibliometric analysis was used to explore the dynamic trends of articles and the top subject areas, journals, institutes, citations, and co-keywords. VOS viewer software (version 1.6.15) was used to graphically map the hot topics of SAP based on the co-keywords.A total of 151 articles were identified. Articles have increased over the recent years and faster in the last 2 years (55 articles, 36.4%), the majority of subject areas are medicine (124 articles, 82.1%) and neuroscience (38 articles, 25.2%). The "Journal Of Stroke And Cerebrovascular Diseases" with 15 articles has been scored as the first rank followed by "Plos One." Regarding the geographical distribution of articles, China is the most productive country with 50 articles (33.1%), others are more prominent in Europe, and most institutes are universities. Citations have increased over time, the main country of the top five highly cited published articles are Germany and before 2008. The co-keywords are mainly divided into four aspects: risk factors, predictive scores, preventions, and outcomes.This study could provide practical sources for researchers to find the top subject areas, journals, institutes, citations, and co-keywords. Moreover, the study could pave the way for researchers to be engaged in studies potentially lead to more articles in this field.


Assuntos
Bibliometria , Pneumonia/etiologia , Acidente Vascular Cerebral/complicações , Humanos , Estudos Retrospectivos
10.
Nano Lett ; 21(18): 7862-7869, 2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34494442

RESUMO

Blocking energy metabolism of cancer cells and simultaneously stimulating the immune system to perform immune attack are significant for cancer treatment. However, how to potently deliver different drugs with these functions remains a challenge. Herein, we synthesized a nanoprodrug formed by a F127-coated drug dimer to inhibit glycolysis of cancer cells and alleviate the immunosuppressive microenvironment. The dimer was delicately constructed to connect lonidamine (LND) and NLG919 by a disulfide bond which can be cleaved by excess GSH to release two drugs. LND can decrease the expression of hexokinase II and destroy mitochondria to restrain glycolysis for energy supply. NLG919 can reduce the accumulation of kynurenine and the number of regulatory T cells, thus alleviating the immunosuppressive microenvironment. Notably, the consumption of GSH by disulfide bond increased the intracellular oxidative stress and triggered immunogenic cell death of cancer cells. This strategy can offer more possibilities to explore dimeric prodrugs for synergistic cancer therapy.


Assuntos
Antineoplásicos , Neoplasias , Pró-Fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Glicólise , Morte Celular Imunogênica , Imunossupressão , Neoplasias/tratamento farmacológico , Polímeros/uso terapêutico , Pró-Fármacos/uso terapêutico
11.
BMJ Open ; 11(9): e049581, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489283

RESUMO

OBJECTIVES: To evaluate the cost-effectiveness of four different primary screening strategies: high-risk factor questionnaire (HRFQ) alone, single immunochemical faecal occult blood test (iFOBT), double iFOBT and HRFQ+double iFOBT for colorectal cancer (CRC) screening compared with no screening using the Markov model. METHODS: Treeage Pro V.2011 software was used to simulate the Markov model. The incremental cost-effectiveness ratio, which was compared with the willingness-to-pay (WTP) threshold, was used to reflect the cost-effectiveness of the CRC screening method. One-way sensitivity analysis and probabilistic sensitivity analysis were used for parameter uncertainty. RESULTS: All strategies had greater effectiveness because they had more quality-adjusted life years (QALYs) than no screening. When the WTP was ¥435 762/QALY, all screening strategies were cost-effective compared with no screening. The double iFOBT strategy was the best-buy option compared with all other strategies because it had the most QALYs and the least cost. One-way sensitivity analysis showed that the sensitivity of low-risk adenoma, compliance with colonoscopy and primary screening cost were the main influencing factors comparing single iFOBT, double iFOBT and HRFQ+double iFOBT with no screening. However, within the scope of this study, there was no fundamental impact on cost-effectiveness. Probabilistic sensitivity analysis showed that when the WTP was ¥435 762/QALY, the probabilities of the cost-effectiveness acceptability curve with HRFQ alone, single iFOBT, double iFOBT and HRFQ+double iFOBT were 0.0%, 5.3%, 69.3% and 25.4%, respectively. CONCLUSIONS: All screening strategies for CRC were cost-effective compared with no screening strategy. Double iFOBT was the best-buy option compared with all other strategies. The significant influencing factors were the sensitivity of low-risk polyps, compliance with colonoscopy and cost of primary screening.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , China , Colonoscopia , Neoplasias Colorretais/diagnóstico , Análise Custo-Benefício , Humanos , Cadeias de Markov , Programas de Rastreamento , Sangue Oculto , Anos de Vida Ajustados por Qualidade de Vida
12.
Hum Reprod ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34590680

RESUMO

STUDY QUESTION: Is CDC26 a key factor in human oocyte aging? SUMMARY ANSWER: The lack of CDC26 disrupts the oocytes maturation process, leading to oocyte aging, but these defects could be partially rescued by overexpression of the CDC26 protein. WHAT IS KNOWN ALREADY: Age-related oocyte aging is the main cause of female fertility decline. In mammalian oocytes, aberrant meiosis can cause chromosomal abnormalities that might lead to infertility and developmental disorders. CDC26 participates in the meiosis process. STUDY DESIGN, SIZE, DURATION: Differential gene expression in young and old women oocytes were screened by single-cell RNA-seq technology, and the functions of differentially genes were verified on mouse oocytes. Finally, transfection technology was used to evaluate the effect of a differentially expressed gene in rescuing human oocyte from aging. PARTICIPANTS/MATERIALS, SETTING, METHODS: Discarded human oocytes were collected for single-cell RNA-seq, q-PCR and immunocytochemical analyses to screen for and identify differential gene expression. Female KM mice oocytes were collected for IVM of oocytes, q-PCR and immunocytochemical analyses to delineate the relationships between oocyte aging and differential gene expression. Additionally, recombinant lentiviral vectors encoding CDC26 were transfected into the germinal vesicle oocytes of older women, to investigate the effects of the CDC26 gene expression on oocyte development. MAIN RESULTS AND THE ROLE OF CHANCE: Many genes were found to be differentially expressed in the oocytes of young versus old patients via RNA-seq technology. CDC26 mRNA and protein levels in aged oocytes were severely decreased, when compared with the levels observed in young oocytes. Moreover, aged oocytes lacking CDC26 were more prone to aneuploidy. These defects in aged oocytes could be partially rescued by overexpression of the CDC26 protein. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Our study delineated key steps in the oocyte aging process by identifying the key role of CDC26 in the progression of oocyte maturation. Future studies are required to address whether other signaling pathways play a role in regulating oocyte maturation via CDC26 and which genes are the direct molecular targets of CDC26. WIDER IMPLICATIONS OF THE FINDINGS: Our results using in vitro systems for both mouse and human oocyte maturation provide a proof of principle that CDC26 may represent a novel therapeutic approach against maternal aging-related spindle and chromosomal abnormalities. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from the National Natural Science Foundation of China (81571442 and 81170571), the outstanding Talent Project of Shanghai Municipal Commission of Health (XBR2011067) and Clinical Research and Cultivation Project in Shanghai Municipal Hospitals (SHDC12019X32). The authors declare no conflict of interest.

13.
Small ; 17(41): e2103986, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34510759

RESUMO

Injecting micro/nanorobots into the body to kill tumors is one of the ultimate ambitions for medical nanotechnology. However, injecting current micro/nanorobots based on 3D-printed biocompatible materials directly into blood vessels for targeted therapy is often difficult, and mistakes in targeting can cause serious side effects, such as blood clots, oxidative stress, or inflammation. The natural affinity of macrophages to tumors, and their natural phagocytosis and ability to invade tumors, make them outstanding drug delivery vehicles for targeted tumor therapy. Hence, a magnetically controlled cell robot (MCR) based on a macrophage drug carrier is proposed. Here, living macrophages are converted into MCRs through endocytosis of specially-designed magnetic nanoparticles loaded with doxorubicin and indocyanine green. Following this, the MCRs can be transported to tumors through the blood vessels using external magnetic fields, and penetrate the blood vessels into the interior of the tumor due to their deformability. With the MCR's cascaded drug release, targeted killing of tumors in mice is demonstrated, with minimal effects on the normal surrounding tissue. The ability to impart precise drug doses onto natural cells, such as macrophages, and load various functional components into the MCRs, offers an efficient method for precise targeted therapy.

14.
Diagn Pathol ; 16(1): 67, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34332589

RESUMO

BACKGROUND: Sudden cardiac death (SCD) remains a great health threat and diagnostic challenge, especially those cases without positive autopsy findings. Molecular biomarkers have been urgently needed for the diagnosis of SCD displaying negative autopsy results. Due to their nature of stability, microRNAs (miRNAs) have emerged as promising diagnostic biomarkers for cardiovascular diseases. METHODS: This study investigated whether specific cardio-miRNAs (miR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p) could serve as potential biomarkers for the diagnosis of SCD. Thirty-four SCD cases were selected, 18 categorized as SCD with negative autopsy (SCD-negative autopsy) findings and 16 as SCD with positive autopsy (SCD-positive autopsy) findings such as coronary atherosclerosis and gross myocardial scar. Carbon monoxide (CO) intoxication (n = 14) and fatal injury death (n = 14) that displayed no pathological changes of myocardium were selected as control group, respectively. Histological analyses were performed to reveal the pathological changes and real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression of those miRNAs. RESULTS: It showed that heart samples from the SCD-negative autopsy group displayed no remarkable difference with regard to the expression of cleaved-caspase3, CD31, and CD68 and the extent of fibrotic tissue accumulation when compared with control samples. The four cardio-miRNAs were significantly up-regulated in the SCD samples as compared with control. When discriminating SCD from controls, receiver operating characteristic (ROC) curve analysis revealed that the areas under the curve (AUC) of these 4 miRNAs were from 0.7839 to 0.9043 with sensitivity of 64.71-97.06% and specificity of 70-100%. Moreover, when discriminating the specific causes of SCD, the four miRNA expressions increased in the heart from the SCD-negative autopsy group as relative to that from the SCD-positive autopsy group, and a combination of two miRNAs presented higher diagnostic value (AUC = 0.7407-0.8667). CONCLUSION: miR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p may serve as independent diagnostic biomarkers for SCD, and a combination of two of these miRNAs could further discriminate detailed causes of SCD.

15.
Ecotoxicol Environ Saf ; 223: 112601, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34385060

RESUMO

Although standard two-dimensional (2D) cell culture is an effective tool for cell studies, monolayer cultivation can yield imperfect or misleading information about numerous biological functions. In this study, we developed an alveolar-capillary exchange (ACE) chip aiming to simulate the cellular microenvironment at the alveolar-capillary interface. The ACE chip was designed with two chambers for culturing alveolar epithelial cells and vascular endothelial cells separately, which are separated by a microporous polycarbonate film that allows for the exchange of soluble biomolecules. Using this model, we further tested the toxic effects of fine particulate matter (PM2.5), a form of airborne pollutant known to induce adverse effects on human respiratory system. These effects are largely associated with the ability of PM2.5 to penetrate the alveoli, where it negatively affects the pulmonary function. Our results indicate that alveolar epithelial cells cultured in the ACE chip in solo and coculture with vascular endothelial cells underwent oxidative injury-induced apoptosis mediated via the PEAK-eIF2α signaling pathway of endoplasmic reticulum stress. The use of ACE chip in an alveolar epithelial cell-vascular endothelial cell coculture model revealed cellular vulnerability to PM2.5. Therefore, this chip provides a feasible surrogate approach in vitro for investigating and simulating the cellular microenvironment responses associated with ACE in vivo.


Assuntos
Poluentes Atmosféricos , Poluentes Atmosféricos/toxicidade , Células Epiteliais Alveolares , Células Endoteliais , Humanos , Pulmão , Material Particulado/toxicidade
16.
Anal Chem ; 93(34): 11751-11757, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34398599

RESUMO

Developing nanoplatforms that simultaneously integrate diagnostic imaging and therapy functions has been a promising but challenging task for cancer theranostics. Herein, we report the rational design of a smart nucleic acid-gated covalent organic framework (COF) nanosystem for cancer-specific imaging and microenvironment-responsive drug release. Cy5 dye-labeled single-stranded DNA (ssDNA) for mRNA recognition was adsorbed on the surface of doxorubicin (Dox)-loaded COF nanoparticles (NPs). Dox loaded in the pores of COF NPs could strengthen the interactions between ssDNA and COF and enhance the fluorescence quenching effect toward Cy5, while the densely coated ssDNA could prevent the leakage of Dox from COF NPs. The obtained nanosystem exhibited low fluorescence signal and Dox release in normal cells; however, the ssDNA could be released by the overexpressed TK1 mRNA in cancer cells to recover the intense fluorescence signal of Cy5, and the loaded Dox could be further released for chemotherapy. Therefore, cancer cell-specific diagnostic imaging and drug release were realized with the rationally developed nanosystem. This work offers a universal nanoplatform for cancer theranostics and a promising strategy for regulating the interaction between COFs and biomolecules.


Assuntos
Estruturas Metalorgânicas , Nanopartículas , Neoplasias , Ácidos Nucleicos , Diagnóstico por Imagem , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico
17.
Cell Biol Toxicol ; 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34458952

RESUMO

Clarithromycin (CLA) has been widely used in the treatment of bacterial infection. Research reveals the adverse effects on the central nervous system among patients receiving CLA treatment; whereas, a relevant underlying mechanism remains considerably unclear. According to our research, an integrated lipidomic and transcriptomic analysis was applied to explore the effect of CLA on neurobehavior. CLA treatment caused anxiety-like behaviors dose-dependently during open field as well as elevated plus maze trials on mice. Transcriptomes and LC/MS-MS-based metabolomes were adopted for investigating how CLA affected lipidomic profiling as well as metabolic pathway of the cerebral cortex. CLA exposure greatly disturbed glycerophospholipid metabolism and the carbon chain length of fatty acids. By using whole transcriptome sequencing, we found that CLA significantly downregulated the mRNA expression of CEPT1 and CHPT1, two key enzymes involved in the synthesis of glycerophospholipids, supporting the findings from the lipidomic profiling. Also, CLA causes changes in neuronal morphology and function in vitro, which support the existing findings concerning neurobehavior in vivo. We speculate that altered glycerophospholipid metabolism may be involved in the neurobehavioral effect of CLA. Our findings contribute to understanding the mechanisms of CLA-induced adverse effects on the central nervous system. 1. Clarithromycin treatment caused anxiety-like behavior with dose-dependent response both in the open field and elevated plus maze test in mice; 2. Clarithromycin exposing predominately disturbed the metabolism of glycerophospholipids in the cerebral cortex of mice; 3. Clarithromycin application remarkably attenuated CEPT1 and CHPT1 gene expression, which participate in the last step in the synthesis of glycerophospholipids; 4. The altered glycerophospholipid metabolomics may be involved in the abnormal neurobehavior caused by clarithromycin.

18.
Genes Brain Behav ; : e12765, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34355499

RESUMO

Previous investigations have implicated the basolateral amygdala (BLA) epigenetic mechanisms in the pathophysiology of depression. SIRT1 is a NAD+-dependent class III histone deacetylase, widely expresses in BLA. However, epigenetic mechanisms in the BLA under the regulation of SIRT1 in the depression are largely uncharacterized. Under the chronic unpredictable chronic mild stress (CUMS) mouse model, we used adeno-associated viral vectors (AAV) that encoded SIRT1-shRNA or SIRT1 to specifically knockdown or overexpress SIRT1 in BLA neurons, respectively. CUMS procedure induced significant depression symptoms including the decreased sucrose preference, the less bodyweight gained, the decreased immobile latency and the increased immobile time both in forced swim test (FST) and tail suspension test (TST). Knockdown of SIRT1 in BLA glutamatergic neurons reversed these depression-like behaviors and restored the synaptic abnormalities. Overexpression of SIRT1 in BLA glutamatergic neurons induced depression-like behaviors in non-stressed control mice. The result of protein expressions and ultrastructural changes were consistent with the behavioral results. Our study suggested that downregulation of SIRT1 in BLA has certain beneficial effect on CUMS-induced depression-like behaviors such as anorexia, anhedonia, hopelessness and despair. In addition, the increased expression of SIRT1 may be the immediate cause of depressive-like symptoms. The abnormal expression of SIRT1 may affect the transcriptional regulation mechanism and signaling protein acetylation, affecting neuroplasticity and ultimately contribute to MDD. In the stress-susceptible mice, these two mechanisms may co-exist, but the specific mechanism needs further research.

19.
Plant J ; 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34369010

RESUMO

Plants interact with other organisms employing volatile organic compounds (VOCs). The largest group of plant-released VOCs are terpenes, comprised of isoprene, monoterpenes, and sesquiterpenes. Mono- and sesquiterpenes are well-known communication compounds in plant-insect interactions, whereas the smallest, most commonly emitted terpene, isoprene, is rather assigned a function in combating abiotic stresses. Recently, it has become evident that different volatile terpenes also act as plant-to-plant signaling cues. Upon being perceived, specific volatile terpenes can sensitize distinct signaling pathways in receiver plant cells, which in turn trigger plant innate immune responses. This vastly extends the range of action of volatile terpenes, which not only protect plants from various biotic and abiotic stresses, but also convey information about environmental constraints within and between plants. As a result, plant-insect and plant-pathogen interactions, which are believed to influence each other through phytohormone crosstalk, are likely equally sensitive to reciprocal regulation via volatile terpene cues. Here, we review the current knowledge of terpenes as volatile semiochemicals and discuss why and how volatile terpenes make good signaling cues. We discuss how volatile terpenes may be perceived by plants, what are possible downstream signaling events in receiver plants, and how responses to different terpene cues might interact to orchestrate the net plant response to multiple stresses. Finally, we discuss how the signal can be further transmitted to the community level leading to a mutually beneficial community-scale response or distinct signaling with near kin.

20.
Biosci Rep ; 41(8)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34339487

RESUMO

miR-219-5p has been reported to act as either a tumor suppressor or a tumor promoter in different cancers by targeting different genes. In the present study, we demonstrated that miR-219-5p negatively regulated the expression of TBXT, a known epithelial-mesenchymal transition (EMT) inducer, by directly binding to TBXT 3'-untranslated region. As a result of its inhibition on TBXT expression, miR-219-5p suppressed EMT and cell migration and invasion in breast cancer cells. The re-introduction of TBXT in miR-219-5p overexpressing cells decreased the inhibitory effects of miR-219 on EMT and cell migration and invasion. Moreover, miR-219-5p decreased breast cancer stem cell (CSC) marker genes expression and reduced the mammosphere forming capability of cells. Overall, our study highlighted that TBXT is a novel target of miR-219-5p. By suppressing TBXT, miR-219-5p plays an important role in EMT and cell migration and invasion of breast cancer cells.

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