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1.
Nat Commun ; 15(1): 3235, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622157

RESUMO

Conformational arrangements within nanostructures play a crucial role in shaping the overall configuration and determining the properties, for example in covalent/metal organic frameworks. In on-surface synthesis, conformational diversity often leads to uncontrollable or disordered structures. Therefore, the exploration of controlling and directing the conformational arrangements is significant in achieving desired nanoarchitectures. Herein, a conformationally flexible precursor 2,4,6-tris(3-bromophenyl)-1,3,5-triazine is employed, and a random phase consisting of C3h and Cs conformers is firstly obtained after deposition of the precursor on Cu(111) at room temperature to 365 K. At low coverage (0.01 ML) selenium doping, we achieve the selectivity of the C3h conformer and improve the nanopore structural homogeneity. The ordered two-dimensional metal organic nanostructure can be fulfilled by selenium doping from room temperature to 365 K. The formation of the conformationally flexible precursor on Cu(111) is explored through the combination of high-resolution scanning tunneling microscopy and non-contact atomic force microscopy. The regulation of energy diagrams in the absence or presence of the Se atom is revealed by density functional theory calculations. These results can enrich the on-surface synthesis toolbox of conformationally flexible precursors, for the design of complex nanoarchitectures, and for future development of engineered nanomaterials.

2.
Immunology ; 172(1): 127-143, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38332630

RESUMO

Myeloid-derived suppressor cells (MDSCs) increase in number and gain immunosuppressive functions in tumours and many other pathological conditions. MDSCs are characterized by their strong T-cell immunosuppressive capacity. The effects that MDSCs may have on B cells, especially within the tumour microenvironment, are less well understood. Here, we report that either monocytic MDSCs or polymorphonuclear MDSCs can promote increases in interleukin (IL)-10-expressing CD19hiFcγRIIbhi regulatory B cells in vitro and in vivo. Splenic transitional-1, -2, and -3 cells and marginal zone B cells, but not follicular B cells, differentiate into IL-10-expressing CD19hiFcγRIIbhi regulatory B cells. The adoptive transfer of CD19hiFcγRIIbhi regulatory B cells via tail vein injection can promote subcutaneous 3LL tumour growth in mice. The expression of programmed death-ligand 1 on MDSCs was found to be strongly associated with CD19hiFcγRIIbhi regulatory B cell population expansion. Furthermore, the frequency of circulating CD19+FcγRIIhi regulatory B cells was significantly increased in advanced-stage lung cancer patients. Our results unveil a critical role of MDSCs in regulatory B-cell differentiation and population expansion in lung cancer patients.


Assuntos
Linfócitos B Reguladores , Neoplasias Pulmonares , Células Supressoras Mieloides , Camundongos , Humanos , Animais , Linfócitos B Reguladores/metabolismo , Células Supressoras Mieloides/metabolismo , Antígeno B7-H1/metabolismo , Diferenciação Celular , Camundongos Endogâmicos C57BL , Microambiente Tumoral
3.
J Sep Sci ; 47(3): e2300847, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38356235

RESUMO

In this work, the potential synergetic effect between deep eutectic solvents and an antibiotic chiral selector (clindamycin phosphate) for enantioseparation was investigated in capillary electrophoresis. We synthesized a series of deep eutectic solvents with choline chloride as hydrogen bond acceptor and three α-hydroxyl acids (l-lactic acid, l-malic acid, and l-tartaric acid) as hydrogen bond donors. Compared to the single clindamycin phosphate separation system, significantly improved separations of model drugs were observed in several synergetic systems. Compared to deep eutectic solvents with a single hydrogen bond donor, deep eutectic solvents with mixed-type hydrogen bond donors were superior. The influences of several key parameters including the type and proportion of organic modifier, clindamycin phosphate concentrations, deep eutectic solvents concentrations, and buffer pH were investigated in detail. The mechanism of the enhanced separations in deep eutectic solvents systems was investigated by means of electroosmotic flow analysis, nuclear magnetic resonance analysis, and molecular modeling. It was the first time that the synergetic systems between deep eutectic solvents and antibiotic chiral selector were established in capillary electrophoresis, and these deep eutectic solvents were demonstrated to have a good synergetic effect with clindamycin phosphate for enantioseparation.


Assuntos
Antibacterianos , Clindamicina/análogos & derivados , Solventes Eutéticos Profundos , Estereoisomerismo , Antibacterianos/química , Eletroforese Capilar/métodos , Solventes/química
4.
Anal Bioanal Chem ; 416(6): 1417-1425, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38240794

RESUMO

Recently, deep eutectic solvents (DESs) have attracted considerable interest in analytical chemistry. This work described the enantioseparations of twenty amino alcohol drugs with several DESs based on lactobionic acid (LA) as the sole chiral selector in capillary electrophoresis (CE) firstly. Compared to the single LA system and the ionic liquid/LA synergistic system, the DES system exhibited considerably improved separations. The influences of some key parameters on separations were investigated in detail. This work also experimentally demonstrated that the carboxyl group was indispensable in the process of chiral recognition. The mechanisms of the improvements of DESs on enantioseparations were studied via ultraviolet spectroscopy. Furthermore, the proposed method was used to determine the enantiomeric purity of propranolol hydrochloride successfully. This is the first time that chiral DESs were utilized as the sole chiral selectors in CE, and this strategy has opened up a new prospect for the use of DESs in enantioseparation.

5.
BMC Endocr Disord ; 23(1): 271, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057752

RESUMO

BACKGROUND: The association involving N6-methyladenosine (m6A) modification, molecular subtype and specific immune cell group in tumor microenvironment has been the focus of recent studies. The underlying function of m6A modification in thyroid cancer (TC) remains elusive. METHODS: The m6A modification regulations, molecular character and tumor immune profile of 461 TC patients were explored and then the correlation between them were comprehensively evaluated. The m6Ascore was established using principal component analysis (PCA) to quantify the m6A pattern of individual TC patients. The prognostic significance of the m6Ascore was evaluated by multivariate Cox regression analysis. RESULTS: Four m6Aclusters (mc1, 2, 3, 4)-characterized by differences in extent of aneuploidy, expression of immunomodulatory genes, mRNA or lncRNA expression pattern and prognosis were identified. T Preliminary validation of m6Ascore was a potential independent prognostic factor of TC involving in mc3. Finally, the prognostic value of the m6Ascore and its association with copy number variation (CNV) and tumor immune microenvironment (TIME) of TC in mc3 were verified. CONCLUSIONS: The correlation between m6A modification, the copy number burden and tumor immune landscape in TC was demonstrated. A m6Acluster-mc3 with low m6Ascore and high CNV molecular subtype was identified with poor clinical prognosis, low infiltrating immunocyte and weak effector T cell. A three-gene clinical prognosis model for TC based on 4 m6a cluster expression was established. Understanding of TIME is enhanced by comprehensive assessment of m6A patterns in individual TC patients and gives a new insight toward improved immunotherapy strategies for TC cancer patients.


Assuntos
Variações do Número de Cópias de DNA , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/genética , Adenina , Imunomodulação , Microambiente Tumoral/genética
6.
Front Immunol ; 14: 1247288, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38022677

RESUMO

Introduction: Low-grade glioma (LGG) is a prevalent malignant tumor in the intracranial region. Despite the advancements in treatment methods for this malignancy over the past decade, significant challenges still persist in the form of drug resistance and tumor recurrence. The Notch signaling pathway plays essential roles in many physiological processes as well as in cancer development. However, the significance of the pathway and family genes in LGG are poorly understood. Methods: We conducted gene expression profiling analysis using the TCGA dataset to investigate the gene set associated with the Notch signaling pathway. we have proposed a metric called "NotchScore" that quantifies the strength of the Notch signaling pathway and enables us to assess its significance in predicting prognosis and immune response in LGG. We downregulated JAG1 in low-grade gliomas to assess its influence on the proliferation and migration of these tumors. Ultimately, we determined the impact of the transcription factor VDR on the transcription of PDL1 through chip-seq data analysis. Results: Our findings indicate that tumors with a higher NotchScore, exhibit poorer prognosis, potentially due to their ability to evade the anti-tumor effects of immune cells by expressing immune checkpoints. Among the genes involved in the Notch signaling pathway, JAG1 has emerged as the most representative in terms of capturing the characteristics of both NotchScore and Notch pathways. The experimental results demonstrate that silencing JAG1 yielded a significant decrease in tumor cell proliferation in LGG cell lines. Our study revealed mechanisms by which tumors evade the immune system through the modulation of PDL1 transcription levels via the PI3K-Akt signaling pathway. Additionally, JAG1 potentially influences PDL1 in LGG by regulating the PI3K-Akt signaling pathway and the expression of the transcription factor VDR. Discussion: These findings contribute to our understanding of immune evasion by tumors in LGG. The insights gained from this research may have implications for the development of therapeutic interventions for LGG.


Assuntos
Glioma , Fosfatidilinositol 3-Quinases , Humanos , Proteínas Proto-Oncogênicas c-akt , Recidiva Local de Neoplasia , Glioma/genética , Prognóstico , Imunidade , Fatores de Transcrição , Proteína Jagged-1/genética
7.
J Nanobiotechnology ; 21(1): 281, 2023 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-37598162

RESUMO

BACKGROUND: Iron sulfide nanomaterials have been successfully employed as therapeutic agents for bacterial infection therapy and catalytic-ferroptosis synergistic tumor therapy due to their unique structures, physiochemical properties, and biocompatibility. However, biomedical research and understanding of the biological functions of iron sulfides are insufficient, and how iron sulfide nanomaterials affect reactive oxygen species (ROS) in diseases remains unknown. Acute kidney injury (AKI) is associated with high levels of ROS, and therefore nanomedicine-mediated antioxidant therapy has emerged as a novel strategy for its alleviation. RESULTS: Here, mackinawite nanozymes were synthesized from glutathione (GSH) and iron ions (Fe3+) (denoted as GFeSNs) using a hydrothermal method, and then evaluated as ROS scavengers for ROS-related AKI treatment. GFeSNs showed broad-spectrum ROS scavenging ability through synergistic interactions of multiple enzymes-like and hydrogen polysulfide-releasing properties. Furthermore, both in vitro and in vivo experiments demonstrated that GFeSNs exhibited outstanding cytoprotective effects against ROS-induced damage at extremely low doses and significantly improved treatment outcomes in AKI. CONCLUSIONS: Given the synergetic antioxidant properties and high biocompatibility, GFeSNs exhibit great potential for the treatment of AKI and other ROS-associated diseases.


Assuntos
Injúria Renal Aguda , Antioxidantes , Animais , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio , Injúria Renal Aguda/tratamento farmacológico , Ferro , Peixes , Glutationa
8.
BMC Cancer ; 23(1): 514, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37280528

RESUMO

BACKGROUND: The association involving mismatch repair (MMR) genes, molecular subtype and specific immune cell group in tumor microenvironment has been focused by more recent studies. Its prognosis value in lung adenocarcinoma (LUAD) neoadjuvant chemotherapy remains elusive. METHODS: The correlation between the MMR gene patterns and the immune landscape were comprehensively evaluated. The MMRScore was calculated using principal component analysis (PCA) after grouping using R/mclust package. The prognostic significance of the MMRScore was evaluated by Kaplan-merrier analysis. Then a cohort of 103 Chinese LUAD patients was collected for neoadjuvant chemotherapy prognosis evaluation and validation using MMRScore. RESULTS: Four MMRclusters (mc1, 2, 3, 4)-characterized by differences in extent of aneuploidy, expression of immunomodulatory (IM) genes, mRNA expression, lncRNA expression and prognosis were identified. We established MMRscore to quantify the MMR pattern of individual LUAD patients. As is shown in further analyses, the MMRscore was a potential independent prognostic factor of LUAD. Finally, the prognostic value of the MMRscore and its association with tumor immune microenvironment (TIME) of LUAD were verified in Chinese LUAD cohort. CONCLUSIONS: We demonstrated the correlation between MMR gene pattern, the CNV and tumor immune landscape in LUAD. A MMRcluster mc2 with high MMRscore, high TMB and high CNV subtype was identified with poor prognosis and infiltrating immunocyte. The comprehensive evaluation of MMR patterns in individual LUAD patients enhances the understanding of TIME and gives a new insight toward improved immune treatment strategies for LUAD patients compared to neoadjuvant chemotherapy.


Assuntos
Neoplasias Pulmonares , Terapia Neoadjuvante , Humanos , Reparo de Erro de Pareamento de DNA/genética , Imunoterapia , Imunomodulação , Pulmão , Prognóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Microambiente Tumoral/genética
9.
Talanta ; 260: 124657, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37187030

RESUMO

Determining glucose in biological samples is tedious and time-consuming due to sample pretreatment. The sample is usually pretreated to remove lipids, proteins, hemocytes and other sugars that interfere with glucose detection. A surface-enhanced Raman scattering (SERS) active substrate based on hydrogel microspheres has been developed to detect glucose in biological samples. Due to the specific catalytic action of glucose oxidase (GOX), the high selectivity of detection is guaranteed. The hydrogel substrate prepared by microfluidic droplets technology protects the silver nanoparticles from the surrounding environment and improves the stability and reproducibility of the assay. In addition, the hydrogel microspheres have size-adjustable pores that selectively allow small molecules to pass through. The pores block the entry of large molecules, such as impurities, enabling glucose detection through glucose oxidase etching without sample pretreatment. This hydrogel microsphere-SERS platform is highly sensitive and enables reproducible detection of different glucose concentrations in biological samples. The use of SERS to detect glucose provides clinicians with new diagnostic methods for diabetes and a new application opportunity for SERS-based molecular detection techniques.


Assuntos
Nanopartículas Metálicas , Microesferas , Nanopartículas Metálicas/química , Glucose , Análise Espectral Raman/métodos , Glucose Oxidase , Hidrogéis , Reprodutibilidade dos Testes , Prata/química
10.
J Am Chem Soc ; 145(11): 6203-6209, 2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36897772

RESUMO

Elimination reactions are one of the most important reactions in organic synthesis, especially in the formation of alkenes and alkynes. Herein, based on scanning tunneling microscopy, we report the bottom-up synthesis of one-dimensional carbyne-like nanostructures, metalated carbyne ribbons with the incorporation of Cu or Ag atoms, through α- and ß-elimination reactions of tetrabromomethane and hexabromoethane on surfaces. Density functional theory calculations demonstrate a width-dependent band gap modulation within these ribbon structures, which is affected by interchain interactions. Moreover, mechanistic insights into the on-surface elimination reactions have also been provided in this study.

11.
J Cancer Res Clin Oncol ; 149(10): 6967-6977, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36849756

RESUMO

PURPOSE: To explore transcriptome and immunological features of patients with Ewing sarcoma (ES) using all publicly available microarray data. METHODS: Data of 479 ES tissues were integrated and normalized. Gene expression, immune infiltration, and cancer-specific pathways were analyzed. Genes of interest were knocked down, followed by cell proliferation and colony formation assays. RESULTS: Consistent with the previous reports of differential expressed genes (DEGs) in ES, our analysis identified CCND1, HMCN1, and NKX2-2 were among the most highly expressed, while TWNC1, MYBPC1, and CKM were among the lowest expressed genes. GO, KEGG, and GSEA enrichment analysis identified that the DEGs related to bone and muscle functioning, those that contributed to crucial cellular, and metabolism pathways such as actin binding, apoptosis, TCA cycle, and cell cycle were also significantly enriched. Immune infiltration analysis discovered that many T cell subsets including CD4T, CD8 T, and Gamma delta T cells were highly infiltrated, while monocytes and B cells were less infiltrated in tumors. A total of 138 genes were both significantly up-regulated in tumors and associated with decreased survival, while 38 significantly down-regulated genes were associated with increased survival, many of which were previously reported as oncogenes and tumor suppressors in ES and other cancers. Silencing of four newly identified top ranked up-regulated genes with decreased survivals in ES inhibited proliferation and colony formation of ES cells. CONCLUSION: This study may provide a clear representative transcriptome profile of ES, providing diagnostic biomarkers, pathways, and immune infiltrative characteristics targets for ES.


Assuntos
Sarcoma de Ewing , Humanos , Sarcoma de Ewing/genética , Sarcoma de Ewing/patologia , Transcriptoma , Proliferação de Células/genética , Apoptose/genética
12.
Analyst ; 148(6): 1322-1329, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36853240

RESUMO

The discovery of novel chiral selectors always fascinates us. This work describes the chiral separation performances of a new chiral selector (kasugamycin, KAS) in capillary electrophoresis (CE) for six pairs of stereoisomers, including ephedrine and pseudoephedrine, quinine and quinidine, cinchonine and cinchonidine, and amlodipine, promethazine and ofloxacin enantiomers. Kasugamycin, an aminoglycoside antibiotic in agriculture, shows significant biological activity against rice blast with low toxicity. As it turns out, this new chiral selector possesses good CE compatibility and stereoselectivity towards model analytes. In this work, we systematically investigated several separation parameters including kasugamycin concentration, buffer pH, separation voltage and the composition of the buffer solution. A detailed discussion about the chiral recognition mechanism was made based on Statistical Product and Service Solution (SPSS) analysis, NMR experiments (1D and 2D) and molecular modeling. This is the first time that kasugamycin is utilized as a chiral selector in CE, and the development of new chiral selectors from agricultural or veterinary antibiotics deserves more attention.


Assuntos
Aminoglicosídeos , Antibacterianos , Antibacterianos/química , Ofloxacino , Eletroforese Capilar/métodos , Estereoisomerismo , Concentração de Íons de Hidrogênio
13.
Int Immunopharmacol ; 117: 109907, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36827915

RESUMO

Circular RNAs (circRNAs) are a subclass of noncoding RNAs and widely involve in the occurrence of multiple human diseases. It is an urgent task to clarify circRNA upstream regulation mechanism and seek their biofunction. Our previous study has confirmed that circular RNA HIPK2 (circHIPK2) promotes astrocyte activation via SIGMAR1, sigma non-opioid intracellular receptor 1, in a mouse model of single high-dose lipopolysaccharide (LPS) injection. However, what mechanism circHIPK2 is regulated by and whether it is involved in the inflammatory response of astrocytes remain unclear. In this study, we reported that circHIPK2 and SIGMAR1 were significantly increased in mouse prefrontal cortex after multiple intraperitoneal injection of LPS, with the elevation of inflammatory mediators. Knockdown circHIPK2 in primary astrocytes suppressed the SIGMAR1 expression and inflammation. Pretreatment of autophagy inducer rapamycin on astrocytes suppressed the circHIPK2 expression and inactivated inflammatory response. These results implied that autophagy inducer rapamycin could suppress astrocytic inflammation by inactivating circHIPK2-SIGMAR1 axis. Autophagy may be a promising upstream administrator of circHIPK2 and therapeutic target for central nervous system inflammation.


Assuntos
Lipopolissacarídeos , RNA Circular , Camundongos , Animais , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Lipopolissacarídeos/metabolismo , Astrócitos/metabolismo , Autofagia , Inflamação/metabolismo , Sirolimo , Proteínas de Transporte/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo
15.
J Oncol ; 2022: 9772208, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467497

RESUMO

Background: The association involving cuprotosis, molecular subtype, and specific immune cell groups in the tumor microenvironment has been focused on by more recent studies. In lung adenocarcinoma (LUAD), the potential functions of cuprotosis remain elusive. Methods: The cuprotosis regulations and tumor immune profile of 567 LUAD patients and the correlation between the cuprotosis patterns and the immune landscape were comprehensively evaluated. The cuprotosisScore was calculated using principal component analysis (PCA). The prognostic significance of the cuprotosisScore was evaluated by Cox regression statistics analysis. Results: Five cuprotosisClusters (named mc1, 2, 3, 4, 5)-characterized by differences in expression of immunomodulatory genes, mRNA, or lncRNA expression, and prognosis were identified. We established cuprotosisScore to quantify the cuprotosis pattern of individual LUAD patients. As is shown in further analyses, the cuprotosisScore was a relatively potential independent prognostic factor of LUAD involved in mc1. Finally, the prognostic value of the cuprotosisScore and its association with tumor immune microenvironment (iTME) of LUAD in five cuprotosisClusters were verified. Conclusions: We demonstrated the correlation between cuprotosis modification, the molecular subtype, and tumor immune landscape in LUAD. The cuprotosisCluster with high cuprotosisScore and high tumor mutation burden (TMB) was identified with a good prognosis and immune functions. The comprehensive evaluation of cuprotosis patterns in individual LUAD patients enhances the understanding of iTME and gives a new insight toward improved immune treatment strategies for LUAD patients.

16.
J Sep Sci ; 45(22): 4070-4078, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36106903

RESUMO

Abemaciclib is an effective selective cyclin-dependent kinases 4 and 6 inhibitors for cancer therapy. The abemaciclib-related substances influence its efficacy and safety, and are important in process preparation studies and quality control. Thus, a reversed-phase high-performance liquid chromatography method was developed and validated for the detection of related substances in its bulk drug. The separation of abemaciclib and related substances was performed on a Phenomenon Gemini C18 column (4.6 × 250 mm, 5 µm) with a flow rate of 1.0 ml/min. The ultraviolet detection wavelength was 280 nm. Mobile phase A was composed of a mixed solution of aqueous solution and acetonitrile (9:1, v/v). The aqueous solution (pH 2.5) contained 0.025-mM potassium dihydrogen phosphate solution and 0.4% triethylamine. Mobile phase B was composed of acetonitrile. This novel method exhibits good system suitability, specificity, precision, stability, linearity (0.1-20 µg/ml), repeatability, and durability. Among abemaciclib and related substances, the lowest limit of detection and quantitation were 0.02 and 0.06 µg/ml, respectively, for abemaciclib. The recovery rates for related substances were above 95%. In addition, a novel degradation product was found during the process. In summary, a reliable reversed-phase high-performance liquid chromatography method was developed for abemaciclib-related substance detection in bulk drugs.


Assuntos
Cromatografia de Fase Reversa , Cromatografia Líquida de Alta Pressão/métodos , Estabilidade de Medicamentos , Cromatografia de Fase Reversa/métodos , Acetonitrilas
17.
J Sep Sci ; 45(18): 3604-3613, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35916273

RESUMO

Taking advantage of chiral ionic liquids, this study deals with the improvement of the enantioseparation performance of a traditional chiral selector (maltodextrin) in capillary electrophoresis. Herein, two polyhydroxy compound-based chiral ionic liquids, namely tetramethylammonium-D-gluconic acid and tetramethylammonium-shikimic acid were designed and utilized as additives for chiral separation for the first time. The synergistic systems provided much better enantioseparations of twelve model drugs compared to the single maltodextrin system. These model analytes contained analgesics, antidepressants, antiallergic drugs, antifungal drugs, antihypertensive drugs, and antiparkinsonian drugs. After optimizing the separation conditions, the chiral recognition mechanism was probed by means of ultraviolet spectroscopy, nuclear magnetic resonance, and molecular modeling. The results of spectroscopic and computational analyses were in good consistency with enantioseparation outcomes. Finally, the proposed method was successfully used for the determination of the enantiomeric purity of duloxetine hydrochloride.


Assuntos
Antialérgicos , Líquidos Iônicos , Antifúngicos , Anti-Hipertensivos , Cloridrato de Duloxetina , Eletroforese Capilar/métodos , Líquidos Iônicos/química , Polissacarídeos , Compostos de Amônio Quaternário , Ácido Chiquímico , Estereoisomerismo
18.
Sci Rep ; 12(1): 12208, 2022 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-35842463

RESUMO

Localized in the mitochondria, SIRT4 is a nicotinamide adenine dinucleotide (NAD +) -dependent adenosine diphosphate (ADP) -ribosyltransferase and is one of the least characterized members of the sirtuin family. Although it is well known that it shows deacetylase activity for energy metabolism, little is understood about its function in tumorigenesis. Recent research suggests that SIRT4 may work as both a tumor suppressor gene and an oncogene. However, the clinical significance of SIRT4 in prostate cancer remains unknown. In this study, we evaluated SIRT4 protein levels in cancerous prostate tissue and corresponding non-tumor prostate tissue via immunohistochemical staining on a tissue microarray including tissues from 89 prostate cancer patients. The association between SIRT4 expression and Gleason score was also determined. Further, shSIRT4 or stable prostate cancer cell lines (22RV1) overexpressing SIRT4 were constructed via lentiviral infection. Using Cell-Counting Kit-8 (CCK-8) assay, wound healing assay, migration, and invasion and apoptosis assays, the effects of SIRT4 on the migration, invasion ability, and proliferation of prostate cancer cells were investigated. We also determined the effect of SIRT4 on glutamine metabolism in 22RV1 cells. We found the protein levels of SIRT4 in prostate cancer tissues were significantly lower than those in their non-neoplastic tissue counterparts (P < 0.01); a lower SIRT4 level was also significantly associated with a higher Gleason score (P < 0.01). SIRT4 suppressed the migration, invasion capabilities, and proliferation of prostate cancer cells and induced cellular apoptosis. Furthermore, the invasion and migration of 22RV1 cells were mechanistically inhibited by SIRT4 via glutamine metabolism inhibition. In conclusion, the present study's findings showed that SIRT4 protein levels are significantly associated with the Gleason score in patients with prostate cancer, and SIRT4 exerts a tumor-suppressive effect on prostate cancer cells by inhibiting glutamine metabolism. Thus, SIRT4 may serve as a potential novel therapeutic target for prostate cancer.


Assuntos
Neoplasias da Próstata , Sirtuínas , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Genes Supressores de Tumor , Glutamina/metabolismo , Humanos , Masculino , Proteínas Mitocondriais/metabolismo , NAD/metabolismo , Neoplasias da Próstata/genética , Sirtuínas/genética , Sirtuínas/metabolismo
19.
ACS Nano ; 16(6): 9843-9851, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35657207

RESUMO

Polycyclic hydrocarbons (PHs) share the same hexagonal structure of sp2 carbons as graphene but possess an energy gap due to quantum confinement effect. PHs can be synthesized by a bottom-up strategy starting from small building blocks covalently bonded into large 2D organic sheets. Further investigation of the role of the covalent bonding/coupling ways on their electronic properties is needed. Here, we demonstrate a surface-mediated synthesis of hexa-peri-hexabenzocoronene (HBC) and its extended HBC oligomers (dimers, trimers, and tetramers) via single- and triple-coupling ways and reveal the implication of different covalent bonding on their electronic properties. High-resolution low-temperature scanning tunneling microscopy and noncontact atomic force microscopy are employed to in situ determine the atomic structures of as-synthesized HBC oligomers. Scanning tunneling spectroscopy measurements show that the length extension of HBC oligomers narrows the energy gap between highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO). Furthermore, the energy gaps of triple-coupling HBC oligomers are smaller and decrease more significantly than that of the single-coupling ones. We hypothesize that the triple coupling promotes a more effective delocalization of π-electrons than the single coupling, according to density functional theory calculations. We also demonstrate that the HBC oligomers can further extend across the substrate steps to achieve conjugated polymers and large-area porous carbon networks.

20.
Oncol Lett ; 24(2): 251, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35761941

RESUMO

Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer, and its development, growth, and invasiveness are regulated by the tumor microenvironment (TME). Insulin-like growth factor-binding protein-7 (IGFBP7), which is closely related to various tumors, transforming growth factor-ß1 (TGFß1), which is a key signal mediator in oncogenesis, α-smooth muscle actin (α-SMA), and collagen I are important components of the TME. IGFBP7 can upregulate the expression of TGFß1 and activate the TGFß1/SMAD signaling pathway, which leads to an increase in collagen I in hepatic stellate cells (HSCs). However, the contribution of IGFBP7 to TGFß1 and the TME in the progression of ESCC remains unknown. In the present study, we investigated IGFBP7 expression and its effects on TGFß1 and the TME in ESCC. A total of 45 patients were divided into three groups: early-tumor group (n=15), advanced-tumor group (n=15), and paracancer control group (n=15). The EC109 cell line was cultured and treated with AdIGFBP7 and LvshTGFß1, and the expression levels of IGFBP7, TGFß1, α-SMA, collagen I, and p-SMAD2/3 were determined by immunohistochemical staining and western blotting analysis. IGFBP7, TGFß1, α-SMA, and collagen I were upregulated in the ESCC samples compared with the control samples (P<0.05), and the values peaked in the advanced-tumor group (P<0.05). Compared with the control group, the TGFß1, α-SMA, p-SMAD2/3, and collagen I proteins were gradually increased from 24 to 72 h in the EC109 cells treated with AdIGFBP7 (P<0.05). Inhibition of TGFß1 expression in the EC109 cells treated with AdIGFBP7 gradually reduced the expression of α-SMA, collagen I, and p-SMAD2/3 from 24 to 72 h (P<0.05). These findings suggest that increased IGFBP7 may accelerate the progression of ESCC by upregulating TGFß1, α-SMA, and collagen I via activating the TGFß1/SMAD signaling pathway, which could remodel the TME.

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