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1.
Yi Chuan ; 44(4): 275-288, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35437236

RESUMO

Enhancer is a DNA sequence, and mainly acts in cis to regulate gene transcription. Due to the uncertainty in both location and distance between enhancers and their target genes, it is more complex and difficult to study the underlying regulatory mechanism of enhancers. Accumulating evidences indicate that enhancers are closely associated with the occurrence and development of diseases, such as cancer. Therefore, the studies of enhancers in cancer will be helpful to deeply unravel cancer pathogenesis and to promote the development of antitumor drugs. The related research is with great social significance and economic value. Currently, the identification of enhancers is insufficient. The regulatory mechanisms by enhancers during the initiation and progression of cancer and other diseases have not been fully delineated. In this review, we provide an overview of enhancers, super enhancers and their properties, followed by a description of enhancer prediction and identification at the genome-wide level. Finally, we summarize the regulatory roles of enhancers during diseases such as cancer in recent years, thereby providing a reference for the future exploration on enhancer regulatory mechanisms as well as cancer diagnosis and treatment.


Assuntos
Elementos Facilitadores Genéticos , Neoplasias , Humanos , Neoplasias/genética
2.
Anal Chim Acta ; 1206: 339798, 2022 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-35473863

RESUMO

Adenosine triphosphate (ATP) is an important biomolecule, which is the primary source of cellular energy. In particular, an abnormal metabolism of ATP level has been took part in many diseases, such as cancer. Thus, developing an effective fluorescent probe for tumor-targeting imaging of ATP is great importance for in-depth understanding the functions of ATP in tumor invasion and matastasis. In this work, we present the design and synthesis of a tumor-targeting near-infrared (NIR) fluorescent probe named Bio-SiR. Bio-SiR is mainly composed of three parts: si-rhodamine-based fluorophore, diethylenetriamine-based recognition group and biotin-based tumor-targetable group. When Bio-SiR reacts with ATP, a turn-on fluorescence at 675 nm (NIR region) is observed clearly, which is suitable for its application in mice. In addition, due to a concurrent effect from dual recognition sites, the probe Bio-SiR displays excellent selectivity for ATP over other potential biological analytes. Under the guidance of biotin group, Bio-SiR can be successfully used for imaging ATP in cancer cells. Furthermore, live-cell imaging allows us to directly real-time monitor the dynamic change of ATP in cancer cells. In particular, this is the first tumor-targeting NIR small-molecule fluorescent probe for endogenous ATP imaging in tumor-bearing mice. These features demonstrate that this probe is a useful imaging tool for expounding the function of ATP in cancer.


Assuntos
Corantes Fluorescentes , Neoplasias , Trifosfato de Adenosina , Animais , Biotina , Camundongos , Neoplasias/diagnóstico por imagem , Rodaminas
3.
Anal Chem ; 94(14): 5514-5520, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35360906

RESUMO

Hydrogen sulfide (H2S) is an important endogenous gas signal molecule in living system, which participates in a variety of physiological processes. Very recent evidence has accumulated to show that endogenous H2S is closely associated with various cancers and can be regarded as a biomarker of cancer. Herein, we have constructed a new near-infrared fluorescent probe (DCP-H2S) based on isophorone-xanthene dye for sensing hydrogen sulfide (H2S). The probe shows remarkable NIR turn-on signal at 770 nm with a large Stokes shift of 200 nm, together with high sensitivity (15-fold) and rapid detection ability for H2S (4 min). The probe also possesses excellent selectivity for H2S over various other analytes including biothiols containing sulfhydryl (-SH). Moreover, DCP-H2S has been successfully applied to visualize endogenous and exogenous H2S in living cells (293T, Caco-2 and CT-26 cells). In particular, the excellent ability of DCP-H2S to distinguish normal mice and tumor mice is shown, and it is expected to be a powerful tool for detection of H2S in cancer diagnosis.


Assuntos
Corantes Fluorescentes , Sulfeto de Hidrogênio , Animais , Células CACO-2 , Células HeLa , Humanos , Camundongos , Imagem Óptica
4.
Adv Sci (Weinh) ; 9(14): e2104333, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35403837

RESUMO

Coronavirus disease 2019 (COVID-19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID-19 hyperimmune globulin (COVID-HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP-CorV (Sinopharm COVID-19 vaccine). COVID-HIG shows high-affinity binding to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, the receptor-binding domain (RBD), the N-terminal domain of the S protein, and the nucleocapsid protein; and blocks RBD binding to human angiotensin-converting enzyme 2 (hACE2). Pseudotyped and authentic virus-based assays show that COVID-HIG displays broad-spectrum neutralization effects on a wide variety of SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) in vitro. However, a significant reduction in the neutralization titer is detected against Beta, Delta, and Omicron variants. Additionally, assessments of the prophylactic and treatment efficacy of COVID-HIG in an Adv5-hACE2-transduced IFNAR-/- mouse model of SARS-CoV-2 infection show significantly reduced weight loss, lung viral loads, and lung pathological injury. Moreover, COVID-HIG exhibits neutralization potency similar to that of anti-SARS-CoV-2 hyperimmune globulin from pooled convalescent plasma. Overall, the results demonstrate the potential of COVID-HIG against SARS-CoV-2 infection and provide reference for subsequent clinical trials.

5.
Brain Res Bull ; 185: 39-48, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35452749

RESUMO

Remote ischemic postconditioning (RIPostC) is a protective procedure for brain damage caused by ischemia/reperfusion (IR), yet the mechanism of this treatment remains to be elucidated. Circular RNAs (circRNAs) are endogenous non-coding RNAs that have recently been recognized to play vital roles in ischemic brain injury. The aim of this study was to explore the role of circRNAs in the protective mechanism of RIPostC and to analyze the circRNA-microRNA (miRNA) regulation network in RIPostC. Nine rats were assigned randomly into three groups (three rats per group): sham, IR, and RIPostC. Their brain tissues were extracted for next-generation RNA sequencing and bioinformatics analysis was performed for two comparisons: sham vs. IR and IR vs. RIPostC. The expression patterns of selected circRNAs and miRNAs were validated by quantitative real-time PCR (qPCR). We detected 82 upregulated and 51 downregulated circRNAs and 137 upregulated and 127 downregulated miRNAs in the IR group compared with the sham group, and 41 upregulated and 100 downregulated circRNAs and 45 upregulated and 64 downregulated miRNAs in the RIPostC group compared with the IR group. The proposed competitive endogenous RNA (ceRNA) network, which included 24 circRNAs, 20 miRNAs, and 145 mRNAs, indicated that the dysregulated circRNAs played important roles in brain IR injury. On the basis of the expression patterns of selected circRNAs, miRNAs, and mRNAs obtained by qPCR, we proposed a circRNA_0002286-miR-124-3p-VLCAD pathway. In PC12 cell, the expression level of miR-124-3p was significantly upregulated when the expression of circRNA_0002286 was repressed and the expression level of VLCAD (very-long chain acyl-CoA dehydrogenase) was significantly downregulated, which suggested that circRNA_0002286 may act as a miRNA sponge for miR-124-3p to regulate the expression of VLCAD. We found that upregulation of circRNA_0002286 attenuated IR injury and was associated with downregulation of miR-124-3p and upregulation of VLCAD. This is the first time that circRNAs have been shown to be closely related to brain IR injury and RIPostC and suggests that targeting the circRNA_0002286-miR-124-3p-VLCAD pathway might attenuate brain IR injury.

6.
Talanta ; 243: 123398, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35325748

RESUMO

Carbon monoxide (CO), as one of significant gas transmitter, is closely associated with a variety of physiological and pathological processes. Although plenty of fluorescent probes have been prepared for detecting CO, most of them suffer from water-soluble fluorophores and short emission wavelength, which tends to diffuse and is limited to apply in vivo. Herein, a novel water-soluble fluorescent probe (HPQ-MQ-CO) is prepared to detect CO by releasing a precipitating fluorochrome (HPQ-MQ-OH), which is developed by introducing the 1-ethyl-2-methylquinoline group into HPQ to obtain long emission wavelength and good diffusion resistant ability. Allyl formate, as the identification unit of CO, has good water solubility and quenches the fluorescence of HPQ-MQ-CO. When the probe reacts with CO and Pd2+, an long-emission and solid-state fluorescence signal at 650 nm can be observed, which is based on excited-state intramolecular proton transfer (ESIPT) mechanism. When the concentration of CO is raised to 100.0 µM, the fluorescence is increased 29 times, indicating the sensitivity of the probe. Moreover, this probe shows prominent selectivity for CO compared with other interfering species. Given these advantages, HPQ-MQ-CO can be used for CO detection in HepG2 cells and zebrafish by in-situ and long-term fluorescence imaging. In addition, this probe can monitor the up-regulation of CO in HepG2 cells and zebrafish during drug-induced liver injury (DILI).


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Corantes Fluorescentes , Animais , Monóxido de Carbono , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico por imagem , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Corantes Fluorescentes/toxicidade , Imagem Óptica/métodos , Peixe-Zebra
7.
Respir Res ; 23(1): 66, 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35313881

RESUMO

The globally increasing annual incidence of chronic obstructive pulmonary disease (COPD), a common chronic disease, poses a serious risk to public health. Although the exact mechanism underlying the pathogenesis of COPD remains unclear, a large number of studies have shown that its pathophysiology and disease course are closely related to oxidative stress, inflammation, apoptosis, autophagy, and aging. The key players involved in COPD include the sirtuin family of NAD-dependent deacetylases that comprise seven members (SIRT1-7) in mammals. Sirtuins play an important role in metabolic diseases, cell cycle control, proliferation, apoptosis, and senescence. Owing to differences in subcellular localization, sirtuins exhibit anisotropy. In this narrative review, we discuss the roles and molecular pathways of each member of the sirtuin family involved in COPD to provide novel insights into the prevention and treatment of COPD and how sirtuins may serve as adjuvants for COPD treatment.


Assuntos
Doença Pulmonar Obstrutiva Crônica/enzimologia , Sirtuínas/fisiologia , Remodelação das Vias Aéreas/fisiologia , Progressão da Doença , Humanos , Inflamação/enzimologia , Inflamação/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia
8.
Nanoscale ; 14(10): 3808-3817, 2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-35191447

RESUMO

Cancer is a major public health problem worldwide, and traditional chemotherapy or a single therapeutic strategy often fails to achieve expected results in cancer treatment. Thus, the development of a method to realize controlled drug delivery and synergistic therapy is required. Herein, MOF-based nanoparticles named RhI-DOX-GOD@ZIF-90 are synthesized using RhI (a near-infrared fluorescent dye), DOX (an anti-cancer drug) and GOD (glucose oxidase). RhI and DOX are encapsulated inside the ZIF-90 framework and GOD is loaded on the surface of ZIF-90. Owing to the fact that the ATP level in cancer cells is abnormally higher than that in normal cells, RhI-DOX-GOD@ZIF-90 nanoparticles are destructed only in cancer cells. RhI is released to give outstanding NIR emission and realize controlled drug delivery. DOX is released and cancer cells are killed by chemotherapy. Also, GOD is released to consume glucose and achieve the purpose of starving the cancer cells. By making full use of the advantages of near-infrared emission, RhI-DOX-GOD@ZIF-90 nanoparticles can be used to image ATP in tumor-bearing mice. At the same time, DOX and GOD can be released accurately at tumor sites of mice and excellent anti-tumor efficiency by synergistic chemotherapy and starvation therapy is achieved.


Assuntos
Doxorrubicina , Nanopartículas , Trifosfato de Adenosina , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Corantes Fluorescentes/farmacologia , Nanopartículas/uso terapêutico
9.
Medicine (Baltimore) ; 101(3): e28494, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35060500

RESUMO

BACKGROUND: Exercise tolerance and lung function can be improved by pulmonary rehabilitation. As a result, it may lower thoracic surgery intensive care unit (ICU) patients' postoperative problems and death. Enhanced recovery after surgery has advanced significantly in the perioperative care of thoracic surgery ICU patients in recent years, and it now plays an essential role in improving ICU patients' postoperative prognosis. Appropriate tailored rehabilitation nursing intervention is required to promote the postoperative recovery of respiratory function in thoracic surgery ICU patients. This study aims to look at the influence of tailored rehabilitation nurse intervention on postoperative respiratory function recovery in thoracic surgery ICU patients. METHODS: To find relevant papers, a comprehensive search of electronic databases will be conducted, including three English databases (PubMed, EMBASE, and the Cochrane Library) and two Chinese databases (Chinese National Knowledge Infrastructure and WanFang). Only research that has been published in either English or Chinese will be considered. The retrieval period will run from November 2021 to November 2021. We will look at randomized controlled trials (RCTs) studies that looked at the effect of a customized rehabilitation nursing intervention on the recovery of respiratory function in thoracic surgery ICU patients after surgery. Two writers will review the literature, retrieve study data, and assess the included studies' quality. Any disagreements will be settled via consensus. RevMan 5.3 will be used to do the meta-analysis. RESULTS: This research will offer high-quality data on the influence of customized rehabilitation nurse intervention on postoperative respiratory function recovery in thoracic surgery ICU patients. CONCLUSION: This study will look at whether a targeted rehabilitation nurse intervention might help thoracic surgery ICU patients recover their respiratory function more quickly after surgery. ETHICS AND DISSEMINATION: There will be no need for ethical approval. REGISTRATION NUMBER: December 12, 2021.osf.io/9rdu2/ (https://osf.io/9rdu2/).


Assuntos
Assistência ao Convalescente , Cuidados de Enfermagem/métodos , Assistência Centrada no Paciente , Cuidados Pós-Operatórios/métodos , Reabilitação , Procedimentos Cirúrgicos Operatórios/reabilitação , Cirurgia Torácica , Humanos , Unidades de Terapia Intensiva , Metanálise como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do Tratamento
10.
Biosci Rep ; 42(1)2022 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-34897384

RESUMO

Treatment of peripheral nerve regeneration with stem cells (SCs) alone has some limitations. For this reason, we evaluate the efficacy of neurotrophic factors combined with stem cell transplantation in the treatment of sciatic nerve injury (SNI) in rats. PubMed, Cochrane Library, Embase, WanFang, VIP and China National Knowledge Infrastructure databases were retrieved from inception to October 2021, and control experiments on neurotrophic factors combined with stem cells in the treatment of SNI in rats were searched. Nine articles and 551 rats were included in the meta-analysis. The results of meta-analysis confirmed that neurotrophic factor combined with stem cells for the treatment of SNI yielded more effective repair than normal rats with regard to sciatic nerve index, electrophysiological detection index, electron microscope observation index, and recovery rate of muscle wet weight. The conclusion is that neurotrophic factor combined with stem cells is more conducive to peripheral nerve regeneration and functional recovery than stem cells alone. However, due to the limitation of the quality of the included literature, the above conclusions need to be verified by randomized controlled experiments with higher quality and larger samples.


Assuntos
Regeneração Nervosa , Nervo Isquiático , Animais , Fatores de Crescimento Neural , Ratos , Transplante de Células-Tronco
11.
Front Psychol ; 13: 764121, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35496250

RESUMO

Deep learning is widely used in the fields of information technology and education innovation but there are few studies for young children in the preschool stage. Therefore, we aimed to explore factors that affect children's learning ability through collecting relevant information from teachers in the kindergarten. Literature review, interview, and questionnaire survey methods were used to determine the influencing factors of deep learning. There were five dimensions for these factors: the level of difficulty of academic, communication skills, level of active collaboration, level of in-depth processing, and reflection level evaluation. Reliability and validity tests were used to analyze the data from questionnaires. In total, 100 valid questionnaires were collected. The Cronbach coefficients for academic challenge, communication, active cooperation, deep processing, and reflective evaluation were 0.801, 0.689, 0.770, 0.758, and 0.665, respectively. Principal component analysis revealed that there were three main factors that affect children's learning depth: the level of deep processing (maximum KMO: 0.908), the level of reflective evaluation (maximum KMO: 0.542), and the active level of collaboration (maximum KMO: 0.410). In conclusion, there were several factors affecting deep learning in children and further studies are warranted to promote the development of this field.

12.
Neural Regen Res ; 17(6): 1299-1309, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34782575

RESUMO

During acute reperfusion, the expression profiles of long noncoding RNAs in adult rats with focal cerebral ischemia undergo broad changes. However, whether long noncoding RNAs are involved in neuroprotective effects following focal ischemic stroke in rats remains unclear. In this study, RNA isolation and library preparation was performed for long noncoding RNA sequencing, followed by determining the coding potential of identified long noncoding RNAs and target gene prediction. Differential expression analysis, long noncoding RNA functional enrichment analysis, and co-expression network analysis were performed comparing ischemic rats with and without ischemic postconditioning rats. Rats were subjected to ischemic postconditioning via the brief and repeated occlusion of the middle cerebral artery or femoral artery. Quantitative real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of differentially expressed long noncoding RNAs after ischemic postconditioning in a rat model of ischemic stroke. The results showed that ischemic postconditioning greatly affected the expression profile of long noncoding RNAs and mRNAs in the brains of rats that underwent ischemic stroke. The predicted target genes of some of the identified long noncoding RNAs (cis targets) were related to the cellular response to ischemia and stress, cytokine signal transduction, inflammation, and apoptosis signal transduction pathways. In addition, 15 significantly differentially expressed long noncoding RNAs were identified in the brains of rats subjected to ischemic postconditioning. Nine candidate long noncoding RNAs that may be related to ischemic postconditioning were identified by a long noncoding RNA expression profile and long noncoding RNA-mRNA co-expression network analysis. Expression levels were verified by quantitative real-time reverse transcription-polymerase chain reaction. These results suggested that the identified long noncoding RNAs may be involved in the neuroprotective effects associated with ischemic postconditioning following ischemic stroke. The experimental animal procedures were approved by the Animal Experiment Ethics Committee of Kunming Medical University (approval No. KMMU2018018) in January 2018.

13.
Chem Commun (Camb) ; 57(100): 13768-13771, 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34859797

RESUMO

A novel theranostic probe called CX-B-DF is constructed for precise chemotherapy guided by near-infrared (NIR) fluorescence imaging. Moreover, the theranostic probe shows high cytotoxicity to cancer cells under dual activation (H2O2 and TP), which causes the accuracy of drug release to be improved and the toxic side effects to be reduced.


Assuntos
Antineoplásicos/uso terapêutico , Ácidos Borônicos/uso terapêutico , Cumarínicos/uso terapêutico , Floxuridina/uso terapêutico , Corantes Fluorescentes/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/metabolismo , Ácidos Borônicos/metabolismo , Linhagem Celular Tumoral , Cumarínicos/metabolismo , Floxuridina/metabolismo , Corantes Fluorescentes/metabolismo , Células HEK293 , Humanos , Peróxido de Hidrogênio/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Neoplasias/diagnóstico por imagem , Imagem Óptica , Medicina de Precisão , Timidina Fosforilase/metabolismo
14.
Biomed Pharmacother ; 144: 112273, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34700232

RESUMO

Neurogenesis in the adult brain is well recognized and plays a critical role in the maintenance of brain function and homeostasis. However, whether neurogenesis also occurs in the adult peripheral nervous system remains unknown. Here, using sensory ganglia (dorsal root ganglia, DRGs) as a model, we show that neurogenesis also occurs in the peripheral nervous system, but in a manner different from that in the central nervous system. Satellite glial cells (SGCs) express the neuronal precursor markers Nestin, POU domain, class 4, transcription factor 1, and p75 pan-neurotrophin receptor. Following sciatic nerve injury, the suppression of endogenous proBDNF by proBDNF antibodies resulted in the transformation of proliferating SGCs into doublecortin-positive cells in the DRGs. Using purified SGCs migrating out from the DRGs, the inhibition of endogenous proBDNF promoted the conversion of SGCs into neuronal phenotypes in vitro. Our findings suggest that SGCs are neuronal precursors, and that proBDNF maintains the SGC phenotype. Furthermore, the suppression of proBDNF signaling is necessary for neuronal phenotype acquisition by SGCs. Thus, we propose that peripheral neurogenesis may occur via the direct conversion of SGCs into neurons, and that this process is negatively regulated by proBDNF.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Gânglios Espinais/metabolismo , Células-Tronco Neurais/metabolismo , Neurogênese , Neuroglia/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Precursores de Proteínas/metabolismo , Potenciais de Ação , Animais , Animais Recém-Nascidos , Fator Neurotrófico Derivado do Encéfalo/genética , Transdiferenciação Celular , Células Cultivadas , Modelos Animais de Doenças , Feminino , Gânglios Espinais/patologia , Gânglios Espinais/fisiopatologia , Masculino , Células-Tronco Neurais/patologia , Neuroglia/patologia , Traumatismos dos Nervos Periféricos/patologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Fenótipo , Precursores de Proteínas/genética , Ratos Sprague-Dawley , Receptores de Fator de Crescimento Neural/genética , Receptores de Fator de Crescimento Neural/metabolismo , Transdução de Sinais
15.
Onco Targets Ther ; 14: 4879-4890, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34588782

RESUMO

PURPOSE: Cisplatin is one of the most widely used antineoplastic drugs but has limited therapeutic effects due to nephrotoxicity. The aim of this study was to determine the possible renoprotective effect of the antioxidant raloxifene on cisplatin-induced nephrotoxicity in mice. MATERIALS AND METHODS: Cisplatin-induced acute renal injury was established in female C57 mice that were treated with saline (normal control) or raloxifene over a 7-day period. The body weight of the mice was recorded. Histopathological examinations of the kidney tissues were performed using H&E, PAS staining and TEM. The histomorphology of liver and other organs was observed by H&E staining. The serum levels of creatinine, blood urea nitrogen (BUN), alanine transaminase (ALT) and glutamic oxalacetic transaminase (AST) were analyzed by specific kits. Superoxide dismutase (SOD) and glutathione (GSH) activity, and the content of malondialdehyde (MDA) in the kidney, liver homogenates and HK-2 cells were measured by WST-8 and thiobarbituric acid colorimetric methods. Moreover, the mitochondrial structures of HK-2 cells were performed using TEM. The viability and proliferation of HK-2 cells were examined by CCK-8 and EdU incorporation assays. The mitochondrial membrane potential was measured by JC-1 fluorescence. RESULTS: Raloxifene significantly reduced the levels of serum creatinine, urea, ALT and AST in the cisplatin-treated mice, and alleviated cisplatin-induced renal and hepatic tissue injury. Furthermore, raloxifene also increased the activity of GSH and SOD in the renal tissues and HK-2 cells, and reduced MDA levels, thereby limiting oxidative stress in the kidney. CONCLUSION: Raloxifene protected against cisplatin-induced nephrotoxicity by activating the antioxidant system, along with alleviating liver damage. It should be considered as a potential adjuvant in cisplatin-based chemotherapeutic protocols.

16.
Anal Chem ; 93(34): 11826-11835, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34461732

RESUMO

Cancer ranks as a leading cause of death in every country of the world. However, if they are discovered early, a lot of cancers can be prevented or cured. Discovering and monitoring cancer markers are the main methods for early diagnosis of cancer. To date, many fluorescent probes designed and used for early cancer diagnosis can only react with a single marker, which always causes insufficient accuracy in complex systems. Herein, a novel near-infrared (NIR) fluorescent probe (CyO-DNP) for the sequential detection of H2S and H+ is synthesized. In this probe, a heptamethine dye is selected as the fluorophore and a 2,4-dinitrophenyl (DNP) ether is chosen as recognition group. In the presence of H2S, CyO-DNP is transformed into CyO, which exhibits an intense fluorescence at 663 nm. Then, H+ induces the protonation of CyO to obtain CyOH, and the final fluorescence emission at 793 nm significantly enhances. Owing to the low cytotoxicity and the NIR fluorescence emission, CyO-DNP can sequentially monitor endogenous H2S and H+ in cancer cells and image exogenous and endogenous H2S and H+ in mice. It is worth mentioning that CyO-DNP can effectively avoid the false positive signal caused by the liver and kidney and discriminate normal mice and tumor mice accurately. For all we know, CyO-DNP is the first fluorescent probe for early accurate diagnosis of cancer by sequentially detecting H2S and H+.


Assuntos
Sulfeto de Hidrogênio , Neoplasias , Animais , Corantes Fluorescentes , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Microscopia de Fluorescência , Neoplasias/diagnóstico
17.
Mikrochim Acta ; 188(9): 287, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34350511

RESUMO

A near-infrared (NIR) fluorescence nanoprobe named RhI-DOX@ZIF-90 has been synthesized by wrapping the guest molecule (RhI and DOX) into ZIF-90 framework. The nanoprobe itself is non-fluorescent and the drug (DOX) is inactive. Upon the addition of ATP, the structure of RhI-DOX@ZIF-90 is degraded. The fluorescence of RhI is recovered and DOX is released. The nanoprobe can detect ATP with high sensitivity and selectivity. There is good linear relationship between the nanoprobe and ATP concentration from 0.25 to 10 mM and the detection limit is 0.10 mM. The nanoprobe has the ability to monitor the change of ATP level in living cells and DOX is released inducing apoptosis of cancer cells. RhI-DOX@ZIF-90 is capable of targeting mitochondria, which provides a basis for improving the efficiency of drug delivery by mitochondrial administration. In particular, the nanoprobe is preferentially accumulated in the tumor sites and detect ATP in tumor mice by fluorescence imaging using near-infrared fluorescence. At the same time, DOX can be released accurately in tumor sites and have good anti-tumor efficiency. So, this nanoprobe is a reliable tool to realize early diagnosis of cancer and improve effect of anticancer drug.


Assuntos
Trifosfato de Adenosina/metabolismo , Antineoplásicos/farmacologia , Preparações de Ação Retardada/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Corantes Fluorescentes/uso terapêutico , Neoplasias/tratamento farmacológico , Humanos
18.
Huan Jing Ke Xue ; 42(9): 4441-4451, 2021 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-34414744

RESUMO

Heavy metals in farmland soil are one of the most hazardous pollutants in the environment, owing to their universality and irreversibility. Modified biochar has been widely used in the adsorption and immobilization of heavy metals in soil, and its applicability is mainly determined by the types of heavy metals, pollution levels, and soil environmental conditions. Soil pollution is gradually becoming more complex and diversified, and heavy metal pollutants mostly occur in the form of compound pollution. However, most studies have focused on single heavy metal pollutant or the addition of heavy metal to soil. This study used rice straw as a raw material to prepare biochar, and modified it with K3PO4, KMnO4, and NaOH. The physicochemical and structural characteristics of the modified biochars were detected using a BET accelerated surface area and porosimetry system, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and the biochars were then analyzed for the availability and forms of Cd and Cu in soils contaminated with heavy metals in the mining area. The results showed that the surface roughness of the modified biochar increased to different degrees with increases in specific surface area and pore volume, with the NaOH modified biochar showing the most significant increases from 4.96 m2·g-1 to 60.79 m2·g-1, and from 0.02 cm3·g-1 to 0.12 cm3·g-1, respectively. The pore diameter changed in the opposite direction. The absorption peaks of the functional groups of the modified biochar were all changed, with K3PO4 modified biochar exhibiting the greatest degree of change. The addition of biochar significantly improved the soil pH value (P<0.05), and the pH value of the soil treated with K3PO4 modified biochar exhibited the largest increase. With an application of 20.5% K3PO4 modified biochar, the availability of Cu and Cd in the soil was significantly reduced, by 75.44% and 67.70%, respectively. The immobilization efficiency of Cu was much higher than that of Cd. The best immobilization efficiency of Cu and Cd in soil was achieved with K3PO4 modified biochar. With an addition of 2% K3PO4 modified biochar, the immobilization efficiency of Cu and Cd was 61.06% and 4.12%, respectively. In summary, K3PO4 modified biochar had a better immobilization effect on both Cu and Cd in compound contaminated soil.


Assuntos
Recuperação e Remediação Ambiental , Poluentes do Solo , Cádmio , Carvão Vegetal , Poluição Ambiental/prevenção & controle , Fazendas , Solo , Poluentes do Solo/análise , Espectroscopia de Infravermelho com Transformada de Fourier
19.
Anal Chim Acta ; 1171: 338655, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34112439

RESUMO

Cysteine (Cys), a kind of small molecule biological thiol, not only involves in the regulation of physiological processes, but also is considered a marker of tumor. However, it is challenging to develop suitable probe for detecting Cys in tumors. In this paper, a near-infrared (NIR) fluorescent probe named IX for Cys has been designed and synthesized. The probe shows a NIR emission peak at 770 nm with large Stokes shift (180 nm) upon adding Cys. It displays high sensitivity to Cys with 6-fold increase of fluorescence intensity. Meanwhile, IX has the high selectivity to Cys over other potential interference such as Hcy and GSH, which have similar structure with Cys. In addition, a possible mechanism of fluorescence enhancement is the reaction of IX with Cys to release IX-OH, which is verified by fluorescence spectra, MS and HPLC. Next, IX can selectively image Cys in HCT-116 cells thanks to the low cytotoxicity. Most important of all, the fluorescent probe IX has visualized Cys in HCT116-xenograft tumor mice due to the near-infrared properties with large Stokes shift.


Assuntos
Cisteína , Corantes Fluorescentes , Animais , Glutationa , Células HCT116 , Humanos , Camundongos , Imagem Óptica
20.
Cancer Manag Res ; 13: 3685-3697, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33994809

RESUMO

AIM: Basal epithelial cells are absent in distant prostate cancer. This study aimed to investigate whether basal epithelial cells could suppress migration and invasion of prostate cancer cells to become a new treatment strategy for prostate cancer. MAIN METHODS: Basal epithelial cells were identified by immunofluorescence with anti-p63. Wound healing assays or transwell assays were used to explore the effects of basal epithelial cells, TGF-ß1, SB431542 (inhibitor of TGF-ß type I receptor) or stattic (inhibitor of phosphorylated STAT3) on migration or invasion of mouse prostate cancer cell (RM-1). Concentration of TGF-ß1 was measured by ELISA assay. HE staining was used to investigate cell morphology. Immunocytochemistry with anti-p63 was used to identify basal epithelial cells. Levels of STAT3, p-STAT3 (Ser727) and proteins associated with EMT were measured with Western blot assay. Cell proliferation was measured with MTT or CCK8 assay. RESULTS: Normal basal epithelial cells acquired from mouse prostate were specific to anti-p63 and more than 90%. Basal epithelial cells and RM-1 could both secrete TGF-ß1. Basal epithelial cells and TGF-ß1 promoted the migration and invasion of RM-1 through changing the cell morphology and up-regulating expression of ZEB1, N-cadherin, vimentin, snail and p-STAT3 (Ser727), at the same time down-regulating E-cadherin of RM-1. SB431542 strongly suppressed migration, invasion as well as the expressions of EMT relevant proteins and p-STAT3 (Ser727) of co-cultured RM-1. In addition, stattic suppressed proliferation, migration and invasion of non-treated RM-1 and co-cultured RM-1. CONCLUSION: Our study suggests that normal basal epithelial cells might stimulate the migration and invasion of RM-1 by TGF-ß1/STAT3 axis which could be suppressed by inhibitor of TGF-ß receptor and inhibitor of p-STAT3. So, basal epithelial cells might not become a treatment strategy for prostate cancer, but our results could provide some researching references for other diseases which include basal epithelial cells such as prostatic intraepithelial neoplasia, prostatic hyperplasia, cervical cancer, or urinary bladder cancer.

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