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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 322: 124802, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38996760

RESUMO

In this work, a near-infrared hepatocyte-targeting fluorescence probe TCF-Gal-Cys was developed. The TCF-Gal-Cys exhibited a low detection limit, good sensitivity and selectivity toward Cys. The responsive mechanism of TCF-Gal-Cys was proposed that the acrylate of TCF-Gal-Cys was subsequently attacked by the thiol group and the amino group of Cys, releasing a strong near-infrared fluorescent group. TCF-Gal-Cys displayed a good hepatocyte-targeting capacity and could specifically distinguish hepatocytes from A549, Hela, SGC-7901 cells because the galactose group of TCF-Gal-Cys can be recognized by HepG2 cells overexpressing ASGPR. The TCF-Gal-Cys has achieved excellently imaging performance to Cys in the zebrafish, so TCF-Gal-Cys has potential to be an effective tool to in real time monitor Cys-related diseases in vitro and in vivo.

2.
Molecules ; 29(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38731452

RESUMO

In this study, two "on-off" probes (BF2-cur-Ben and BF2-cur-But) recognizing acetylcholinesterase (AChE) were designed and synthesized. The obtained probes can achieve recognition of AChE with good selectivity and pH-independence with a linear range of 0.5~7 U/mL and 0.5~25 U/mL respectively. BF2-cur-Ben has a lower limit of detection (LOD) (0.031 U/mL), higher enzyme affinity (Km = 16 ± 1.6 µM), and higher inhibitor sensitivity. A responsive mechanism of the probes for AChE was proposed based on HPLC and mass spectra (MS) experiments, as well as calculations. In molecular simulation, BF2-cur-Ben forms more hydrogen bonds (seven, while BF2-cur-But has only four) and thus has a more stable enzyme affinity, which is mirrored by the results of the comparison of Km values. These two probes could enable recognition of intracellular AChE and probe BF2-cur-Ben has superior cell membrane penetration due to its higher log p value. These probes can monitor the overexpression of AChE during apoptosis of lung cancer cells. The ability of BF2-cur-Ben to monitor AChE in vivo was confirmed by a zebrafish experiment.


Assuntos
Acetilcolinesterase , Corantes Fluorescentes , Animais , Humanos , Acetilcolinesterase/metabolismo , Acetilcolinesterase/química , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Limite de Detecção , Peixe-Zebra
3.
Talanta ; 274: 126060, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38604044

RESUMO

In this study, a lysosomal targeting fluorescent probe recognition on CEs was designed and synthesized. The obtained probe BF2-cur-Mor demonstrated excellent selectivity, sensitivity, pH-independence, and enzyme affinity towards CEs within 5 min. BF2-cur-Mor could enable recognition of intracellular CEs and elucidate that the CEs content of different cancer cells follows the rule of HepG2 > HCT-116 > A549 > HeLa, and the CEs expression level of hepatoma cancer cells far exceeds that of normal hepatic cells, being in good agreement with the previous reports. The ability of BF2-cur-Mor to monitor CEs in vivo was confirmed by zebrafish experiment. BF2-cur-Mor exhibits some pharmacological activity in that it can induce apoptosis in hepatocellular carcinoma cells but is weaker in normal hepatocyte cells, being expected to be a potential "diagnostic and therapeutic integration" tool for the clinical diagnosis of CEs-related diseases.


Assuntos
Corantes Fluorescentes , Peixe-Zebra , Humanos , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Animais , Carboxilesterase/metabolismo , Carboxilesterase/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Desenho de Fármacos
4.
Neuroepidemiology ; 58(3): 182-198, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38295785

RESUMO

OBJECTIVE: The objective of this study was to study the primary risk factors for the long-term trends of mortality rates in ischemic stroke (IS) in China. METHODS: Using the Global Burden of Disease Study 2019 (GBD 2019) database, research was conducted on the 11 primary risk factors for the mortality rates of IS in China from 1990 to 2019. This study employed joinpoint regression software and the age-period-cohort method to evaluate the trends of mortality rates divided by age, period, and cohort over time. RESULTS: From 1990 to 2019, the age-standardized mortality rate (ASMR) caused by a diet high in red meat and high body mass index in China showed an upward trend. ASMR increased first and then decreased due to smoking, diet high in sodium, particulate matter pollution, high fasting plasma glucose, and high systolic blood pressure. Low-density lipoprotein cholesterol (LDL-C), kidney dysfunction, low temperature, and lead exposure remained relatively stable during this period. In the 35-45 age group, the mortality rate of IS due to high LDL-C was up to about 60%, and smoking affected men more than women. Overall, high LDL-C, high systolic blood pressure, and particulate matter pollution were the most common risk factors in patients with IS. The risk of death rose with age. The period and cohort relative risks showed that metabolic risk factors had the greatest impact on the mortality of IS. CONCLUSION: Metabolic risk factors have become the primary risk factors for the ASMR of IS in China. Relevant authorities should pay attention to their long-term effects on IS. Effective public health policies and interventions should be implemented to reduce the burden of IS.


Assuntos
AVC Isquêmico , Humanos , China/epidemiologia , Pessoa de Meia-Idade , Masculino , Feminino , Fatores de Risco , Idoso , Adulto , AVC Isquêmico/mortalidade , AVC Isquêmico/epidemiologia , Estudos de Coortes , Idoso de 80 Anos ou mais , Fatores Etários , Adulto Jovem , Mortalidade/tendências
5.
BMJ Open ; 14(1): e071417, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-38171624

RESUMO

OBJECTIVE: This research aimed to assess the levels of cognitive function and its contributing factors among individuals experiencing cancer pain (CP) in mainland China. DESIGN: A descriptive, cross-sectional study. SETTING: The investigation was undertaken within three tertiary oncology hospitals. PARTICIPANTS: We included 220 hospitalised individuals who reported experiencing cancer-related pain and consented to complete the research questionnaires. OUTCOME MEASURES: The collected data encompassed sociodemographic and clinical variables, augmented by results from validated questionnaires. Cognitive impairment (CI) was evaluated using the Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog) scale, with scores ranging from 0 to 148. Sleep quality, depression and anxiety were assessed through the Pittsburgh Sleep Quality Index, the Patient Health Questionnaire-9 and the Generalised Anxiety Disorder-7, respectively. A binary logistic regression model was used to identify factors associated with CI in individuals with CP. RESULTS: Of the 225 individuals approached, 220 (97.8%) participated in the study. The mean FACT-Cog score for those with CP was 101.29 (SD=25.24; range=25-148). The prevalence of CI among these individuals was 35.90%. Sleep quality was rated below medium in 45% of participants with CP. More than moderate pain was reported by 28.2%, with 64.6% experiencing depression and 38.6% experiencing anxiety. Increased odds of developing CI were observed in those with CP (OR 1.422, 95% CI 1.129 to 1.841), depression (OR 1.119, 95% CI 1.029 to 1.2117), anxiety (OR 1.107, 95% CI 1.005 to 1.220), advancing age (OR 1.042, 95% CI 1.013 to 1.073), poor sleep quality (OR 1.126, 95% CI 1.013 to 1.252) and a history of smoking (OR 3.811, 95% CI 1.668 to 8.707). CONCLUSIONS: CI associated with CP is notably prevalent in China. Those older, with a smoking history, inadequate sleep, more severe pain, depression and anxiety, have a heightened risk of CI. Consequently, interventions need to be personalised, addressing these key determinants.


Assuntos
Dor do Câncer , Neoplasias , Humanos , Dor do Câncer/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Depressão/psicologia , Fatores de Risco , Neoplasias/complicações , Ansiedade/epidemiologia , Ansiedade/psicologia , Dor/epidemiologia , Dor/etiologia , Cognição , China/epidemiologia
6.
J Clin Lab Anal ; 37(23-24): e24990, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38063322

RESUMO

BACKGROUND: Primary hepatocellular carcinoma (HCC) is one of the most prevalent world-wide malignancies. Half of the newly developed HCC occurs in China. Optimizing the strategies for high-risk surveillance and early diagnosis are pivotal for improving 5-year survival. Constructing the scientific non-invasive detection technologies feasible for medical and healthcare institutions is among the key routes for elevating the efficacies of HCC identification and follow-up. RESULTS: Based on the Chinese and international guidelines, expert consensus statements, literatures and evidence-based clinical practice experiences, this consensus statement puts forward the clinical implications, application subjects, detection techniques and results interpretations of the triple-biomarker (AFP, AFP-L3%, DCP) based GALAD, GALAD like models for liver cancer. CONCLUSIONS: The compile of this consensus statement aims to address and push the reasonable application of the triple-biomarker (AFP, AFP-L3%, DCP) detections thus to maximize the clinical benefits and help improving the high risk surveillance, early diagnosis and prognosis of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Biomarcadores Tumorais , alfa-Fetoproteínas , Sensibilidade e Especificidade , Precursores de Proteínas , Protrombina , Biomarcadores , Algoritmos
7.
Foods ; 12(13)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37444244

RESUMO

The effect of chlorogenic acid (CA) on the dielectric response of lotus seed starch (LS) after microwave treatment, the behavior and digestive characteristics of the resulting starch/chlorogenic acid complex (LS-CA) at different degrees of gelatinization and the inhibition of α-amylase by chlorogenic acid were investigated. The variation in dielectric loss factor, ε″, and dielectric loss tangent, tanδε, of the microwave thermal conversion indicated that LS-CA had a more efficient microwave-energy-to-thermal-energy conversion efficiency than LS. This gelatinized LS-CA to a greater extent at any given temperature between 65 and 85 °C than LS, and it accelerated the degradation of the starch crystalline structure. The greater disruption of the crystal structure decreased the bound water content and increased the thermal stability of LS-CA compared to LS. The simulated in vitro digestion found that the presence of the LS-CA complex improved the slow-digestion property of lotus seed starch by increasing its content of resistant and slowly digested starch. In addition, the release of chlorogenic acid during α-amylase hydrolysis further slowed starch digestion by inhibiting α-amylase activity. These findings provide a foundation for understanding the correlation between the complex behavior and digestive properties of naturally polyphenol-rich, starch-based foods, such as LS, under microwave treatment, which will facilitate the development of starch-based foods with tailored digestion rates, lower final degrees of hydrolysis and glycemic indices.

8.
Dalton Trans ; 52(25): 8503-8529, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37312618

RESUMO

Gas sensors are essential for detecting toxic gases that can harm social life or industrial production. Traditional metal oxide semiconductor (MOS)-based sensors suffer from shortcomings such as high operating temperature and slow response time, which limits their detection capabilities. Thus, there is a need to improve their performance. One useful technique is noble metal functionalization, which can effectively enhance the response/recovery time, sensitivity and selectivity, sensing response, and optimum operating temperature of MOS gas sensors. Among the noble metals, Au NPs are considered a promising material for forming composite sensing materials to achieve better sensing performance. This paper aims to review and discuss the recent research on Au-decorated MOS-based sensors, including Au/n-type MOS-based sensors, Au/p-type MOS-based sensors, Au/MOS/carbon composite materials, and Au/MOS/perovskite composite materials. The sensing mechanism of Au-functionalized MOS-based materials will also be examined.

9.
Phytomedicine ; 116: 154896, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37247588

RESUMO

BACKGROUND: Liver metastasis is a frequent event in breast cancer that causes low survival rate and poor prognosis. Citri Reticulatae Pericarpium-Reynoutria japonica Houtt. (CR), a traditional Chinese herb pair, is used for the treatment of breast cancer liver metastasis or cholesterol gallstone disease in clinics. PURPOSE: This study attempted to investigate the potential therapeutic target and mechanism of CR herb pair on breast cancer liver metastasis. METHODS: The anti-metastatic and cholesterol-lowering activities of CR extract were evaluated in triple-negative breast cancer (TNBC) cell lines and an experimental liver metastasis model. The role of extracellular matrix protein 1 (ECM1) in the cholesterol biosynthesis pathway was determined by the knockdown and overexpression of ECM1 gene of TNBC cells. Changes in the gene and protein expression levels of ECM1 and the cholesterol biosynthesis pathway after CR treatment were detected in vitro and in vivo by real-time PCR and Western blot. RESULTS: The invasive and metastatic potentials and hypercholesterol levels of TNBC cells were positively associated with ECM1 expression. ECM1 knockdown reduced tumor cholesterol levels via downregulating cholesterol biosynthesis genes, including ACAT2, HMGCS1, HMGCR, MVK, and MVD, whereas ECM1 overexpression elicited the opposite effects. CR herb pair exerts the potential therapeutic effects on TNBC liver metastasis, which is partially mediated by disrupting ECM1-activated cholesterol biosynthesis process in TNBC cells. CONCLUSION: This study reveals that ECM1 is a novel target for the activation of cholesterol biosynthesis to promote TNBC liver metastasis occurrence. CR herb pair, an ECM1 inhibitor, maybe be considered to serve as an adjuvant therapeutic drug for liver metastasis in clinical practice.


Assuntos
Neoplasias Hepáticas , Neoplasias de Mama Triplo Negativas , Humanos , Reynoutria , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Linhagem Celular Tumoral , Proteínas da Matriz Extracelular
10.
Biomed Pharmacother ; 160: 114319, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36724639

RESUMO

Non-alcoholic fatty liver disease (NAFLD) has become one of the main chronic liver diseases worldwide. Protopanaxadiol (PPD), an active compound derived from Gynostemma pentaphyllum, has been found able to improve free fatty acid-induced lipid accumulation in hepatocytes. However, the efficacy of PPD on NAFLD and the underlying mechanism remains unknown. In this study, the mice were fed with a high-fat diet for 22 weeks to induce the NAFLD model, and then were treated with PPD by gavage for 8 weeks. Moreover, AML12 and HepG2 cells induced by free fatty acids for 24 h, were treated with different doses of PPD and/or AMPK or SIRT1 inhibitor to explore the pharmacological mechanism of PPD. The results showed that mice with PPD treatment had significantly reduced liver weight and serum aminotransferase levels, less severe hepatosteatosis, and inflammatory cell infiltration in liver tissues when compared with the model mice. PPD also reversed the down-regulated activation of AMPK and SIRT1 expression as well as the change of lipid metabolism-related molecules in the mice liver tissues. Consistently, the in vitro experiments showed the effect of PPD in ameliorating lipid accumulation in hepatocytes. The inhibitor of AMPK or SIRT1 suppressed the AMPK and SIRT1 signaling and markedly diminished the anti-steatosis effect of PPD. In conclusion, our results prove the ameliorating impact of PPD on NAFLD and also reveal the involvement of regulation of AMPK/SIRT1 signaling pathway-mediated lipid metabolism in the underlying mechanism, suggesting PPD as a potential natural compound for the treatment of NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Metabolismo dos Lipídeos , Proteínas Quinases Ativadas por AMP/metabolismo , Sirtuína 1/metabolismo , Hepatócitos , Fígado , Transdução de Sinais , Ácidos Graxos não Esterificados/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL
11.
Nat Commun ; 13(1): 4711, 2022 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-35953472

RESUMO

Innate lymphoid cells (ILCs) exert important roles in host defense, tissue repair and inflammatory diseases. However, how ILC lineage specification is regulated remains largely elusive. Here we identify that circular RNA circTmem241 is highly expressed in group III innate lymphoid cells (ILC3s) and their progenitor cells. CircTmem241 deficiency impairs ILC3 commitment and attenuates anti-bacterial immunity. Mechanistically, circTmem241 interacts with Nono protein to recruit histone methyltransferase Ash1l onto Elk3 promoter in ILC progenitor cells (ILCPs). Ash1l-mediated histone modifications on Elk3 promoter enhance chromatin accessibility to initiate Elk3 transcription. Of note, circTmem241-/-, Nono-/- and Ash1l-/- ILCPs display impaired ILC3 differentiation, while Elk3 overexpression rescues ILC3 commitment ability. Finally, circTmem241-/-Elk3-/- mice show lower numbers of ILC3s and are more susceptible to bacterial infection. We reveal that the circTmem241-Nono-Ash1l-Elk3 axis is required for the ILCP differentiation into ILC3P and ILC3 maturation, which is important to manipulate this axis for ILC development on treatment of infectious diseases.


Assuntos
Imunidade Inata , Linfócitos , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas c-ets/metabolismo , Animais , Diferenciação Celular , Proteínas de Ligação a DNA/genética , Histona-Lisina N-Metiltransferase , Linfócitos/metabolismo , Camundongos , RNA Circular , Fatores de Transcrição/metabolismo
12.
Front Chem ; 10: 871659, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35494638

RESUMO

Alternariol (AOH) and alternariol monomethyl ether (AME) are two main Alternaria mycotoxins that endanger human health. In this study, a single-chain antibody fragment (scFv) capable of equivalently and specifically recognizing AOH and AME was first expressed, and its equivalent recognition mechanism was discussed. According to molecular docking and dynamic simulation, the C9 site, which was always exposed outside the binding cavity, made the structural differences between AOH and AME negligible. Due to the high similarity of structures, AOH and AME interacted with almost the same amino acids on the scFv; thus, the same interaction mode and interaction force were produced. This was considered to be the most critical reason for the equivalent recognition. Thus, the exposure of common structures was considered a potential strategy to obtain the equivalent recognition antibodies, and C9 was considered the key site in the process of hapten modification. These results laid a theoretical foundation for further research on antibodies against Alternaria mycotoxins. It could promote the rapid detection of AOH and AME in food and provide a new idea for targeted preparation of antibodies that could recognize multiple hazards with similar structures.

13.
Acta Pharmacol Sin ; 43(6): 1544-1555, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34426644

RESUMO

Metastasis is the leading cause of death in breast cancer patients. Osthole, as an active compound detected in the traditional Chinese medicine Wenshen Zhuanggu Formula, has shown a promising anti-metastatic activity in human breast cancer cells, but the underlying mechanisms remain ambiguous. In this study we elucidated the anti-metastatic mechanisms of osthole in highly metastatic breast cancer cells and a zebrafish xenograft model. We showed that the expression of integrin α3 (ITGα3) and integrin ß5 (ITGß5) was upregulated in highly metastatic MDA-MB-231, MDA-MB-231BO breast cancer cell lines but was downregulated in poorly metastatic MCF-7 breast cancer cell line, which might be the key targets of osthole's anti-metastatic action. Furthermore, we showed that knockdown of ITGα3 and ITGß5 attenuated breast cancer cell migration and invasion possibly via suppression of FAK/Src/Rac1 pathway, whereas overexpression of ITGα3 and ITGß5 caused the opposite effects. Consistently, osthole significantly inhibited breast cancer metastasis by downregulating ITGα3/ITGß5 signaling in vitro and in vivo. These results provide new evidence that osthole may be developed as a candidate therapeutic drug for metastatic breast cancer.


Assuntos
Neoplasias da Mama , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular , Cumarínicos/farmacologia , Cumarínicos/uso terapêutico , Feminino , Humanos , Invasividade Neoplásica/prevenção & controle , Peixe-Zebra
14.
Front Cell Dev Biol ; 9: 758776, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34912802

RESUMO

Colon cancer is a complex, heterogeneous disease. The Colorectal Cancer Subtyping Consortium reported a novel classification system for colon cancer in 2015 to better understand its heterogeneity. This molecular classification system divided colon cancer into four distinct consensus molecular subtypes (CMS 1, 2, 3, and 4). However, the characteristics of different colon cancer molecular subtypes have not been fully elucidated. This study comprehensively analyzed the molecular characteristics of varying colon cancer subtypes using multiple databases and algorithms, including The Cancer Genome Atlas (TCGA) database, DriverDBv3 database, CIBERSORT, and MCP-counter algorithms. We analyzed the alterations in the subtype-specific genes of different colon cancer subtypes, such as the RNA levels and DNA alterations, and showed that specific subtype-specific genes significantly affected prognosis. We also explored the changes in colon cancer driver genes and representative genes of 10 signaling pathways in different subtypes. We identified genes that were altered in specific subtypes. We further detected the infiltration of 22 immune cell types in four colon cancer subtypes and the infiltration level of primary immune cells among these subtypes. Additionally, we explored changes in immune checkpoint genes (ICGs) and immunotherapy responses among different colon cancer subtypes. This study may provide clues for the molecular mechanism of tumorigenesis and progression in colon cancer. It also offers potential biomarkers and targets for the clinical diagnosis and treatment of different colon cancer subtypes.

15.
Nat Commun ; 12(1): 6314, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34728628

RESUMO

Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers and is characterized by high recurrence and heterogeneity, yet its mechanism is not well understood. Here we show that N1-methyladenosine methylation (m1A) in tRNA is remarkably elevated in hepatocellular carcinoma (HCC) patient tumour tissues. Moreover, m1A methylation signals are increased in liver cancer stem cells (CSCs) and are negatively correlated with HCC patient survival. TRMT6 and TRMT61A, forming m1A methyltransferase complex, are highly expressed in advanced HCC tumours and are negatively correlated with HCC survival. TRMT6/TRMT61A-mediated m1A methylation is required for liver tumourigenesis. Mechanistically, TRMT6/TRMT61A elevates the m1A methylation in a subset of tRNA to increase PPARδ translation, which in turn triggers cholesterol synthesis to activate Hedgehog signaling, eventually driving self-renewal of liver CSCs and tumourigenesis. Finally, we identify a potent inhibitor against TRMT6/TRMT61A complex that exerts effective therapeutic effect on liver cancer.


Assuntos
Adenosina/análogos & derivados , Carcinoma Hepatocelular/patologia , Colesterol/metabolismo , Proteínas de Membrana/metabolismo , PPAR gama/metabolismo , RNA de Transferência/metabolismo , tRNA Metiltransferases/metabolismo , Adenosina/química , Adenosina/metabolismo , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Autorrenovação Celular , Modelos Animais de Doenças , Feminino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Proteínas de Membrana/genética , Metilação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Taxa de Sobrevida , tRNA Metiltransferases/genética
16.
Dalton Trans ; 51(1): 27-39, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34812463

RESUMO

The development and application of metal nanoclusters (MNCs) in nucleic acid testing in the past 10 years have been summarized. Fluorescence enhancement and red shift can occur when the G-rich sequence gets close to Ag NCs or the complementary DNA strand hybridizes with Ag NCs tail strand, which can be used to identify the nucleic acid. Ag NCs with the abasic site in DNA duplex can distinguish mutant genes such as cancer suppression gene p53. Ag NCs with auxiliary DNA can be used to detect miR-21, miR-16-5p, miR-19b-3p, and miR-141. Cu NCs/Cu NPs can recognize miRNA-155, miR-21, and miR-let-7d without auxiliary DNA. Au NCs can identify H1N1 gene fragments by fluorescence quenching caused by proximity to the G-rich sequence. Besides, Au NCs can recognize miRNA-21 and let-7a. SsDNA MNCs adsorbed on the surface of GO and CNPs oxide can be used to identify HBV and HIV gene fragments. The addition of enzymes or auxiliary amplification technologies is a popular way to improve probe sensitivity. Ag NCs combined with TAIEA has the best performance and can obtain LOD as low as aM for miRNA.


Assuntos
Metais Pesados/química , MicroRNAs/análise , Nanoestruturas/química
17.
Mol Cancer ; 20(1): 132, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34649567

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most intractable tumors in the world due to its high rate of recurrence and heterogeneity. Liver cancer initiating cells also called cancer stem cells (CSCs) play a critical role in resistance against typical therapy and high tumor-initiating potential. However, the role of the novel circular RNA (circRNA) circIPO11 in the maintenance of liver cancer initiating cells remains elusive. METHODS: CircRNAs highly conserved in humans and mice were identified from 3 primary HCC samples by circRNA array. The expression and function of circIPO11 were further evaluated by Northern blot, limiting dilution xenograft analysis, chromatin isolation by RNA purification-PCR assay (ChIRP) and HCC patient-derived tumor cells (PDC) models. CircIpo11 knockout (KO) mice were generated by a CRISPR/Cas9 technology. RESULTS: CircIPO11 is highly expressed in HCC tumor tissues and liver CSCs. CircIPO11 is required for the self-renewal maintenance of liver CSCs to initiate HCC development. Mechanistically, circIPO11 recruits TOP1 to GLI1 promoter to trigger its transcription, leading to the activation of Hedgehog signaling. Moreover, GLI1 is also highly expressed in HCC tumor tissues and liver CSCs, and TOP1 expression levels positively correlate with the metastasis, recurrence and survival of HCC patients. Additionally, circIPO11 knockout in mice suppresses the progression of chemically induced liver cancer development. CONCLUSION: Our findings reveal that circIPO11 drives the self-renewal of liver CSCs and promotes the propagation of HCC via activating Hedgehog signaling pathway. Antisense oligonucleotides (ASOs) against circIPO11 combined with TOP1 inhibitor camptothecin (CPT) exert synergistic antitumor effect. Therefore, circIPO11 and the Hedgehog signaling pathway may provide new potential targets for the treatment of HCC patients.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Autorrenovação Celular/genética , Proteínas Hedgehog/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Células-Tronco Neoplásicas/metabolismo , RNA Circular , beta Carioferinas/genética , Animais , Biomarcadores Tumorais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Suscetibilidade a Doenças , Dosagem de Genes , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Knockout , Células-Tronco Neoplásicas/patologia , Regiões Promotoras Genéticas , Transdução de Sinais
18.
J Med Chem ; 64(19): 14793-14808, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34595917

RESUMO

One antitumor ß-elemene derivative W-105 and three novel hepatocyte-targeting prodrugs (W-1-5, W-2-9, and W-3-8) were designed and synthesized. W-105 (IC50 6.107 µM) could cause cell apoptosis through upregulating the activity of caspase-3. The hepatocyte-targeting capacities of the aimed compounds followed the W-105 (parent compound) < W-1-5 (monodentate-galactose) < W-2-9 (bidentate-galactose) < W-3-8 (tridentate-galactose) order, which is attributed to the excellent affinity of the galactose ligand to ASGPR and the galactose-cluster recognition effect. Furthermore, prodrugs W-3-8 exhibited good antitumor activity and low toxic side effects. The liquid chromatography-mass spectrometry (LC-MS) assays revealed that prodrugs (W-1-5, W-2-9, and W-3-8) could release the antitumor pharmacophore in the presence of GSH (mimic the condition of the tumor cell) and maintain the low-toxic structures in the absence of GSH (mimic the condition of the normal cell). The release mechanisms of prodrugs were also proposed. Overall, these prodrugs developed in this study had potential in the treatment of liver cancer.


Assuntos
Antineoplásicos/farmacologia , Assialoglicoproteínas/metabolismo , Desenvolvimento de Medicamentos , Glutationa/metabolismo , Hepatócitos/efeitos dos fármacos , Pró-Fármacos/farmacologia , Antineoplásicos/química , Cromatografia Líquida/métodos , Sistemas de Liberação de Medicamentos , Espectrometria de Massas/métodos , Pró-Fármacos/química
19.
J Food Sci Technol ; 58(11): 4157-4166, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34538900

RESUMO

Lotus seed (LS) has a high starch content and possesses many useful functional properties, which are mainly attributed to its phenolic compound content. The objective of this study was to investigate the effect of microwave irradiation (MW) treatment on the structural and physicochemical properties of a lotus seed starch-chlorogenic acid (CA) blend. MW treatment appeared to promote the formation of LS-CA complexes and the modified starch displayed more rougher structures than native starch. The particle size distribution of starch remained approximately constant when the microwave power was 200 W, but increased sharply with further increases in microwave power; a similar trend was observed in the swelling and solubility of starch. XRD and FT-IR spectra show that MW treatment degraded the ordered crystalline structure of starch, facilitating exposure of the starch chains originally buried in the crystalline and amorphous regions within the grains. During this treatment, CA interacted with starch molecules by hydrogen bonding and form a LS-CA complex, which inhibited the self-assembly process of starch chains. These findings demonstrated the potential use of MW treatment in controlling the storage and processing quality of lotus seed, or other starchy foods rich in polyphenols.

20.
Int J Pharm ; 602: 120628, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33892061

RESUMO

Curcumin can induce cancer cell apoptosis through lysosomal permeabilization pathway. However, the poor selectivity of curcumin restricts its use in the therapy of hepatocellular carcinoma. Because galactose group can recognize ASGPR overexpressed on hepatoma cells and morpholine group can target to the lysosome, they are integrated into a dual-targeted lipid material with low toxicity. The corresponding galactose-morpholine modified liposomes loaded with curcumin (Gal-Mor-LPs) were prepared and evaluated in comparison with conventional liposomes (LPs) and galactose modified liposomes (Gal-LPs). The in vitro and in vivo hepatic targeting capacity of liposomes followed a trend of LPs < Gal-LPs < Gal-Mor-LPs. The endocytosis of Gal-Mor-LPs was competitively inhibited by galactose, which confirmed the galactose modified liposomes entered hepatoma cells via ASGPR-mediated pathway. Gal-Mor-LPs displayed more excellent lysosomal targeting efficacy than LPs and Gal-LPs due to the attraction of acidic lysosome on basic morpholine group of Gal-Mor-LPs. The in vivo tumor inhibition effects of formulations also followed a trend of free curcumin < LPs < Gal-LPs < Gal-Mor-LPs, confirming that hepatic and lysosomal dual-targeting vehicle can improve the antitumor efficacy of curcumin. Moreover, the curcumin-loaded liposomes modified with galactose and morpholine moieties show good biocompatibility in vivo.


Assuntos
Carcinoma Hepatocelular , Curcumina , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Galactose , Humanos , Lipossomos , Neoplasias Hepáticas/tratamento farmacológico , Lisossomos
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