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1.
Connect Tissue Res ; 65(4): 293-303, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38884152

RESUMO

BACKGROUND: Previous research has identified a significant role of Thioredoxin-interacting protein (TXNIP) in bone loss. The purpose of this investigation was to assess the role and the underlying molecular mechanisms of TXNIP in the osteogenic differentiation of human bone marrow stromal cells (hBMSCs) and pre-osteoblast MC3T3-E1 cells. METHODS: Human bone marrow stem cells (hBMSCs) and MC3T3-E1 cells were used to induce osteogenic differentiation. The expression of genes and proteins was assessed using RT-qPCR and western blot, respectively. ChIP assay was used to validate the interaction between genes. The osteogenic differentiation ability of cells was reflected using ALP staining and detection of ALP activity. The mineralization ability of cells was assessed using ARS staining. DCFCA staining was employed to evaluate the intracellular ROS level. RESULTS: Initially, downregulation of TXNIP and upregulation of EZH2 were observed during osteogenesis in hBMSCs and MC3T3-E1 cells. Additionally, it was discovered that EZH2 negatively regulates TXNIP expression in these cells. Furthermore, experiments indicated that the knockdown of TXNIP stimulated the activation of the PI3K/AKT/Nrf2 signaling pathway in hBMSCs and MC3T3- E1 cells, thus inhibiting the production of reactive oxygen species (ROS). Further functional experiments revealed that overexpression of TXNIP inhibited the osteogenic differentiation in hBMSCs and MC3T3-E1 cells by enhancing ROS produc-tion. On the other hand, knockdown of TXNIP promoted the osteogenic differentiation capacity of hBMSCs and MC3T3-E1 cells through the activation of the PI3K/AKT/Nrf2 pathway. CONCLUSION: In conclusion, this study demonstrated that TXNIP expression, under the regulation of EZH2, plays a crucial role in the osteogenic differentiation of hBMSCs and MC3T3-E1 cells by regulating ROS production and the PI3K/AKT/Nrf2 pathway.


Assuntos
Proteínas de Transporte , Diferenciação Celular , Proteína Potenciadora do Homólogo 2 de Zeste , Células-Tronco Mesenquimais , Osteogênese , Estresse Oxidativo , Transdução de Sinais , Animais , Humanos , Camundongos , Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Fator 2 Relacionado a NF-E2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Tiorredoxinas
2.
Cell Mol Biol (Noisy-le-grand) ; 70(2): 113-119, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38430033

RESUMO

Strategies targeting lin-28 homolog A (LIN28A) for the treatment of osteosarcoma are limited, even though salient findings have illustrated the crucial role of LIN28A in bone deformities and cancer. In the present study, we proved circ_0096041, one of the circular RNAs (circRNAs) with significant upregulated expression in osteosarcoma, to be notably engaged in the progression of osteosarcoma. We elucidated that osteosarcoma patients with highly expressed circ_0096041 had relatively worse prognoses. We determined that circ_0096041 potentially sponge miR-556-5p using the Circular RNA Interactome database. Meanwhile, we proved circ_0096041 was associated with miR-556-5p. Furthermore, we determined that miR-556-5p was targeted by LIN28A directly, evidenced by in silico analysis using the miRWALK tool and in vitro analysis. Functionally, our experimental setting aimed to explore the function of circ_0096041/miR-556-5p/LIN28A axis in vitro and in vivo. Our findings demonstrated that circ_0096041 boosted the proliferation and migration of osteosarcoma via LIN28A/miR-556-5p axis. In vivo models were further established to estimate the metastasis promoted by circ_0096041. This research elucidated the enhanced osteosarcoma progression by circ_0096041 and its potential mechanism, which provided innovative targets for osteosarcoma treatment.


Assuntos
Neoplasias Ósseas , MicroRNAs , Osteossarcoma , RNA Circular , Humanos , Neoplasias Ósseas/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , MicroRNAs/genética , Osteossarcoma/genética , Osteossarcoma/metabolismo , RNA Circular/genética
3.
BMC Musculoskelet Disord ; 25(1): 671, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39192239

RESUMO

BACKGROUND: Triangular fibrocartilage complex (TFCC) injuries, especially Palmer type IB, pose surgical management challenges due to associated distal radial ulnar joint (DRUJ) instability. Traditional surgeries entail risks of complications. Arthroscopic repair presents advantages but lacks consensus on optimal techniques. To evaluate arthroscopic dual-bone tunnel repair in patients with Palmer type IB TFCC injuries of the wrist. METHODS: In this retrospective case series, grip strength ratio, joint range of motion, pain visual analogue scale (VAS), modified Mayo wrist score, and Disabilities of the Arm, Shoulder, and Hand (DASH) scores were assessed before and 12 months after surgery. RESULTS: The cohort consisted of 45 patients. At 12 months, the grip strength ratio improved from 0.71 ± 0.08 to 0.93 ± 0.05 (P < 0.001), and wrist joint rotation increased from 126.78 ± 13.28° to 145.76 ± 8.52° (P < 0.001). VAS (1.60 ± 0.58 vs. 6.33 ± 0.91, P < 0.001), DASH (12.96 ± 3.18 vs. 46.87 ± 6.62, P < 0.001), and modified Mayo wrist (88.11 ± 4.43 vs. 63.78 ± 7.99, P < 0.001) scores all improved after surgery. The overall complication rate was 4.44%. CONCLUSION: Arthroscopic dual-bone tunnel repair appears to be an effective intervention for alleviating wrist pain, restoring stability, and enhancing joint function in patients with TFCC Palmer type IB injuries.


Assuntos
Artroscopia , Amplitude de Movimento Articular , Fibrocartilagem Triangular , Humanos , Artroscopia/métodos , Masculino , Feminino , Estudos Retrospectivos , Fibrocartilagem Triangular/lesões , Fibrocartilagem Triangular/cirurgia , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Traumatismos do Punho/cirurgia , Resultado do Tratamento , Força da Mão , Articulação do Punho/cirurgia , Articulação do Punho/fisiopatologia
4.
Lipids Health Dis ; 22(1): 182, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37880723

RESUMO

BACKGROUND: Polyunsaturated fatty acids (PUFAs) have demonstrated significant therapeutic potential across a wide range of disease. The aim of this study was to investigate the potential impact of PUFA intake on the prevalence of erectile dysfunction (ED). METHODS: The study included a total of 3730 participants from the National Health and Nutrition Examination Survey (NHANES) 2001-2004. Univariate analysis, multivariate regression analysis, subgroup analysis and machine learning were utilized to explore the relationship of variables to ED. Dose response curves were constructed to observe the linear or nonlinear relationship between PUFA intake and the prevalence of ED. Propensity score matching (PSM) was used for sensitivity analysis. Finally, the potential mechanistic link between PUFA intake and ED was explored. RESULTS: Through univariate and multivariate regression analysis results before and after PSM and XGBoost algorithm model results, arachidonic acid (AA) was chosen as the main research object. The consumption of AA was found to be associated with a decreased prevalence of ED under the fully adjusted model [OR = 0.33 (0.20, 0.56), P < 0.001]. The interaction between AA and education was found in the subgroup analysis. Dose-response curves indicated a linear negative correlation between AA intake and the prevalence of ED. The above results were confirmed in the data analysis after 1:1 PSM. In addition, AA intake was associated with a decrease in inflammatory biomarkers and homocysteine. CONCLUSIONS: The results suggest that AA intake is negatively correlated with the prevalence of ED. Further, anti-inflammatory and anti-endothelial damage may play a role in this.


Assuntos
Disfunção Erétil , Masculino , Humanos , Disfunção Erétil/epidemiologia , Inquéritos Nutricionais , Estudos Transversais , Prevalência , Ácidos Graxos Insaturados , Ácido Araquidônico
5.
Angew Chem Int Ed Engl ; 59(52): 23532-23536, 2020 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-32924253

RESUMO

Described herein is a strategy to construct cationic azahelicenes through the three-component annulation reaction of isoquinoline, indole, and 1,2-dichloroethane (DCE), in which DCE serves as an in situ activating agent for C1-H activation of isoquinoline, a vinyl equivalent, and a solvent. This in situ activation annulation reaction features a facile one-step synthesis and complete regioselectivity. The complete regioselectivity of C1 over C3 for the isoquinoline ring paves a path to the helical structure in a highly ordered sequence. One of the synthesized ionic [5]azahelicenium fluorophores exhibits the potential to serve as a mitochondria-targeted biomarker with good photostability and low cytotoxicity.


Assuntos
Compostos Policíclicos/química , Catálise , Estrutura Molecular , Estereoisomerismo
6.
Angew Chem Int Ed Engl ; 58(1): 254-258, 2019 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-30421489

RESUMO

Reported herein is a rhodium(III)-catalyzed three-component annulation reaction of simple pyridines, alkynes, and 1,2-dichloroethane (DCE), affording a streamlined pathway to diverse ring-fused pyridiniums. DCE not only serves as a vinyl equivalent but also as an in situ activating agent for pyridine C2-H activation. A cationic five-membered rhodacycle complex has been isolated and proposed as a possible intermediate. This strategy can be extended to other N-containing heteroarenes for the synthesis of multiring-fused pyridiniums. These multicomponent reactions exhibit excellent regioselectivity for 1,3-diynes, paving a path to the cascade cyclization of 3-fluoropyridine or N-methylpyridin-3-amine with 1,3-diynes for the construction of brand-new tricyclic-fused pyrano- or hydropyridoquinolizinium salts. These ionic fluorophores have been investigated as potential biomarkers.

7.
J Org Chem ; 83(16): 9538-9546, 2018 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-29979039

RESUMO

A highly efficient palladium-catalyzed direct C-H functionalization/annulation of BODIPYs with alkynes has been developed for the first time to construct a series of unsymmetrical benzo[ b]-fused BODIPYs from readily available starting materials. These unsymmetrical benzo[ b]-fused BODIPYs exhibit remarkably red-shifted emissions and larger Stokes shifts than classical BODIPY dyes. Cell imaging experiments and cytotoxicity assays demonstrate that BODIPYs 4c and 4d have specific lysosome-labeling capacities, turn-on fluorescence emissions in cells, and low cytotoxicity.


Assuntos
Alcinos/química , Compostos de Boro/química , Compostos de Boro/metabolismo , Carbono/química , Hidrogênio/química , Lisossomos/metabolismo , Paládio/química , Catálise , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Células Hep G2 , Humanos , Imagem Óptica
8.
Angew Chem Int Ed Engl ; 57(29): 9108-9112, 2018 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-29862624

RESUMO

By making use of a dual-chelation-assisted strategy, a completely regiocontrolled oxidative C-H/C-H cross-coupling reaction between an N-acylaniline and a benzamide has been accomplished for the first time. This process constitutes a step-economic and highly efficient pathway to 2-amino-2'-carboxybiaryl scaffolds from readily available substrates. A Cp*-free RhCl3 /TFA catalytic system was developed to replace the [Cp*RhCl2 ]2 /AgSbF6 system generally used in oxidative C-H/C-H cross-coupling reactions between two (hetero)arenes (Cp*=pentamethylcyclopentadienyl, TFA=trifluoroacetic acid). The RhCl3 /TFA system avoids the use of the expensive Cp* ligand and AgSbF6 . As an illustrative example, the procedure developed herein greatly streamlines the total synthesis of the naturally occurring benzo[c]phenanthridine alkaloid oxynitidine, which was accomplished in excellent overall yield.

9.
Analyst ; 142(14): 2678, 2017 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-28660925

RESUMO

Correction for 'A universal strategy for visual chiral recognition of α-amino acids with l-tartaric acid-capped gold nanoparticles as colorimetric probes' by Guoxin Song et al., Analyst, 2016, 141, 1257-1265.

10.
Analyst ; 141(4): 1257-65, 2016 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-26759834

RESUMO

The ability to recognize and quantify the chirality of alpha-amino acids constitutes the basis of many critical areas for specific targeting in drug development and metabolite probing. It is still challenging to conveniently distinguish the enantiomer of amino acids largely due to the lack of a universal and simple strategy. In this work, we report a strategy for the visual recognition of α-amino acids. It is based on the chirality of L-tartaric acid-capped gold nanoparticles (L-TA-capped AuNPs, ca. 13 nm in diameter). All of 19 right-handed α-amino acids can induce a red-to-blue color change of L-TA-capped AuNP solution, whereas all of the left-handed amino acids (except cysteine) cannot. The chiral recognition can be achieved by the naked eye and a simple spectrophotometer. This method does not require complicated chiral modification, and excels through its low-cost, good availability of materials and its simplicity. Another notable feature of this method is its high generality, and this method can discriminate almost all native α-amino acid enantiomers. This versatile method could be potentially used for high-throughput chiral recognition of amino acids.


Assuntos
Aminoácidos/química , Colorimetria/métodos , Ouro/química , Nanopartículas Metálicas/química , Tartaratos/química , Cor , Histidina/química , Modelos Moleculares , Conformação Molecular , Tamanho da Partícula , Estereoisomerismo
11.
Anal Bioanal Chem ; 408(7): 1863-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26781100

RESUMO

A simple and rapid method for detection of potassium ion (K(+)) based on a guanine chemiluminescence (CL) system is presented. In this system, one guanine-rich DNA molecule is used as the recognition element. K(+) can cause the guanine-rich DNA to form a G-quadruplex conformation, resulting in remarkable quenching of the guanine CL intensity of guanine-rich DNA. The CL intensity of this CL system decreased with increasing K(+) concentration, revealing a linear relationship in K(+) concentration range from 3 × 10(-5) to 1 × 10(-3) M. A complete detection process can be accomplished in about 5 min. Other common cations (such as Na(+), NH4 (+), Mg(2+), Ca(2+), Zn(2+), and Pb(2+)) did not notably interfere with K(+) detection. The mechanism of this strategy is also discussed. The sensing strategy is low cost and simple without the requirement of complex labeling of probe DNA. The scheme is applicable to the detection of other guanine-rich aptamer-binding chemicals or biomolecules.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Quadruplex G , Guanina/química , Medições Luminescentes/métodos , Potássio/urina , Técnicas Biossensoriais/economia , Humanos , Limite de Detecção , Luminescência , Medições Luminescentes/economia , Modelos Moleculares , Potássio/análise
12.
Anal Chem ; 87(14): 7156-62, 2015 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-26111123

RESUMO

Detection of ultralow concentration of specific DNA sequence is a central challenge in the early diagnosis of gene-related disease and biodefense application. Herein, we report a dual-amplification strategy for highly sensitive fluorescence detection of DNA. In this proposed strategy, a dumbbell-shaped DNA probe is designed to integrate target binding, magnetic separation, and signal response. In the presence of specific DNA target, the multifunctional dumbbell probe can initiate exonuclease III (Exo III)-aided target recycling amplification, and, in the meantime, generate a large number of fluorescein (FAM)-encapsulated liposomes. The developed method offers very high sensitivity due to primary amplification via numerous FAM from a liposome and secondary amplification via target recycling amplification. The detection limit of the proposed method can reach 4 aM, which is much lower than that of the Exo III-aided target recycling technique applied for DNA quantification without FAM-encapsulated liposomes amplification. Moreover, the dual-signal amplification process can be completed one-step in this system. Therefore, this method provides a simple, isothermal, and low-cost approach for sensitive detection of DNA and holds a great potential for early diagnosis in gene-related diseases.


Assuntos
Técnicas Biossensoriais , DNA/análise , Exodesoxirribonucleases/metabolismo , Fluorescência , Lipossomos/metabolismo , Técnicas de Amplificação de Ácido Nucleico , DNA/metabolismo , Exodesoxirribonucleases/química , Fluoresceína/química , Fluoresceína/metabolismo , Lipossomos/química , Tamanho da Partícula
13.
Aging (Albany NY) ; 16(9): 8086-8109, 2024 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-38728245

RESUMO

BACKGROUND: Research has shown a connection between vasculogenic mimicry (VM) and cancer progression. However, the functions of genes related to VM in the emergence and progression of TNBC have not been completely elucidated. METHODS: A survival risk model was constructed by screening biomarkers using DESeq2 and WGCNA based on public TNBC transcriptome data. Furthermore, gene set enrichment analysis was performed, and tumor microenvironment and drug sensitivity were analyzed. The selected biomarkers were validated via quantitative PCR detection, immunohistochemical staining, and protein detection in breast cancer cell lines. Biomarkers related to the proliferation and migration of TNBC cells were validated via in vitro experiments. RESULTS: The findings revealed that 235 target genes were connected to the complement and coagulation cascade pathways. The risk score was constructed using KCND2, NRP1, and VSTM4. The prognosis model using the risk score and pathological T stage yielded good validation results. The clinical risk of TNBC was associated with the angiogenesis signaling pathway, and the low-risk group exhibited better sensitivity to immunotherapy. Quantitative PCR and immunohistochemistry indicated that the expression levels of KCND2 in TNBC tissues were higher than those in adjacent nontumor tissues. In the TNBC cell line, the protein expression of KCND2 was increased. Knockdown of KCND2 and VSTM4 inhibited the proliferation and migration of TNBC cells in vitro. CONCLUSIONS: In this study, three VM-related biomarkers were identified, including KCND2, NRP1, and VSTM4. These findings are likely to aid in deepening our understanding of the regulatory mechanism of VM in TNBC.


Assuntos
Biomarcadores Tumorais , Neovascularização Patológica , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Feminino , Prognóstico , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral/genética , Proliferação de Células/genética , Neuropilina-1/genética , Neuropilina-1/metabolismo , Movimento Celular/genética , Transcriptoma , Canais de Potássio de Domínios Poros em Tandem/genética , Canais de Potássio de Domínios Poros em Tandem/metabolismo
14.
Gene ; 920: 148538, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38710294

RESUMO

To explore whether Fengshi Liuhe Decoction (FLD) alleviates rheumatoid arthritis (RA) via the Fzd6/NF-κB signaling axis. We used real-time quantitative PCR (qPCR) and western blotting (WB) to determine the genes of the frizzled (Fzd) protein 1- Fzd protein 10 that are significantly differentially expressed between normal rat fibroblast-like synoviocyte (FLS) and collagen II-induced arthritis (CIA) rat FLS. Next, we used enzyme-linked immunosorbent assay (ELISA) to evaluate the levels of inflammatory factors in cell culture supernatant to determine the ability of FLD to ameliorate RA. Finally, we employed WB to detect the key gene expression in protein levels of the Fzd6/NF-κB signaling axis among normal rat FLS, CIA rat FLS, and FLD-treated CIA rat FLS. Our results showed that Fzd6 expression was significantly higher in CIA rat FLS at both the mRNA and protein levels than in normal rat FLS. FLD was found to downregulate Fzd6 and inflammatory factors, including COX-2, IL-8, and TNF-α, at both the mRNA and protein levels. FLD was also found to downregulate the total protein levels of Fzd6 and the NF-κB signaling pathway key gene phosphorylation of p-p65/p65 and p-IκBα/IκBα. Moreover, FLD inhibited the nuclear translocation of NF-κB p65 in CIA rat FLS. FLD can alleviate inflammation of CIA rat FLS via the Fzd6/NF-κB signaling axis.


Assuntos
Artrite Reumatoide , Medicamentos de Ervas Chinesas , Receptores Frizzled , NF-kappa B , Transdução de Sinais , Animais , Transdução de Sinais/efeitos dos fármacos , Ratos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Artrite Reumatoide/genética , NF-kappa B/metabolismo , Receptores Frizzled/metabolismo , Receptores Frizzled/genética , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Artrite Experimental/genética , Sinoviócitos/metabolismo , Sinoviócitos/efeitos dos fármacos , Masculino , Células Cultivadas
15.
J Neuroimmune Pharmacol ; 19(1): 24, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38780885

RESUMO

Cornuside has been discovered to improve learning and memory in AD mice, however, its underlying mechanism was not fully understood. In the present study, we established an AD mice model by intracerebroventricular injection of Aß1-42, which were treated with cornuside (3, 10, 30 mg/kg) for 2 weeks. Cornuside significantly ameliorated cognitive function of AD mice in series of behavioral tests, including Morris water maze test, nest building test, novel object recognition test and step-down test. Additionally, cornuside could attenuate neuronal injury, and promote cholinergic synaptic transmission by restoring the level of acetylcholine (ACh) via inhibiting acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), as well as facilitating choline acetyltransferase (ChAT). Furthermore, cornuside inhibited oxidative stress levels amplified as decreased malondialdehyde (MDA), by inhibiting TXNIP expression, improving total anti-oxidative capacity (TAOC), raising activities of superoxide dismutase (SOD) and catalase (CAT). Cornuside also reduced the activation of microglia and astrocytes, decreased the level of proinflammatory factors TNF-α, IL-6, IL-1ß, iNOS and COX2 via interfering RAGE-mediated IKK-IκB-NF-κB phosphorylation. Similar anti-oxidative and anti-inflammatory effects were also found in LPS-stimulated BV2 cells via hampering RAGE-mediated TXNIP activation and NF-κB nuclear translocation. Virtual docking revealed that cornuside could interact with the active pocket of RAGE V domain directly. In conclusion, cornuside could bind to the RAGE directly impeding the interaction of Aß and RAGE, and cut down the expression of TXNIP inhibiting ROS production and oxidative stress, as well as hamper NF-κB p65 mediated the inflammation.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Disfunção Cognitiva , NF-kappa B , Fragmentos de Peptídeos , Receptor para Produtos Finais de Glicação Avançada , Transdução de Sinais , Animais , Camundongos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/induzido quimicamente , Peptídeos beta-Amiloides/toxicidade , Peptídeos beta-Amiloides/metabolismo , Fragmentos de Peptídeos/toxicidade , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/induzido quimicamente , Transdução de Sinais/efeitos dos fármacos , Receptor para Produtos Finais de Glicação Avançada/metabolismo , NF-kappa B/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos
16.
Polymers (Basel) ; 15(14)2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37514489

RESUMO

Disulfide bonds are dynamic covalent bonds, which are easy to cleave and reform upon chemical stimulus. Various methods including the oxidative coupling of thiols and polymerization of disulfide-containing monomers have been developed for the synthesis of poly(disulfide)s. However, installing small amounts of disulfide units in the main chain of polyolefins has received much less attention. Herein, we report a novel strategy for incorporating cleavable disulfide units into the backbone of polyolefins using commercially available diallyl disulfide (DADS) as a comonomer via metathesis copolymerization. The copolymerization of diallyl disulfide with cyclooctene occurred using the second-generation Grubbs catalyst under mild conditions, allowing for the synthesis of copolymers with adjustable disulfide content ranging from 0.7 to 8.5 mol%, and the molecular weight of the obtained copolymers ranged from 5.8 kg·mol-1 to 42.8 kg·mol-1. The resulting polyolefins with disulfide insertion retained excellent thermal processability and exhibited degradability. Treatment of the copolymer (8.5 mol% disulfide content) with tri-n-butylphosphine resulted in a significant reduction in molecular weight from 5.8 kg·mol-1 to 1.6 kg·mol-1. Successful copolymerization with diallyl disulfide provides a convenient and effective method for obtaining degradable polyolefins.

17.
Front Med (Lausanne) ; 10: 1218051, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37636579

RESUMO

Purpose: It is currently controversial whether smoke exposure is associated with the risk of kidney stones. Herein, publicly available databases were combined to explore relationships with the risk of nephrolithiasis in terms of smoking status and serum cotinine concentrations. Materials and methods: First, we conducted an observational study using data from 2007 to 2018, based on the National Health and Nutrition Examination Survey (NHANES) database. Univariate analysis, multivariate logistic regression, trend testing, restricted cubic spline (RCS), and multiple imputation (MI) were the main analytical methods of our study. Then, A Mendelian randomization (MR) analysis was performed to explore the causal relationship between serum cotinine and nephrolithiasis. Genetic instruments for serum cotinine and pooled data for kidney stones were derived from publicly available large-scale genome-wide association studies (GWAS). Inverse-variance weighting (IVW) was the primary method for our MR analysis. Results: A total of 34,657 and 31,352 participants were included in the observational study based on smoking status and serum cotinine concentrations, respectively. Under full adjustment of covariates, current smokers had an increased risk of kidney stones compared to non-smokers [OR = 1.17 (1.04-1.31), P = 0.009, P for trend = 0.010]. Compared with serum cotinine of <0.05 ng/ml, serum cotinine levels of 0.05-2.99 ng/ml [OR = 1.15 (1.03-1.29), P = 0.013] and ≥3.00 ng/ml [OR = 1.22 (1.10-1.37), P < 0.001] were observed to have a higher risk of nephrolithiasis (P for trend < 0.001). In addition, a non-linear relationship between log2-transformed serum cotinine and the risk of nephrolithiasis was found (P for non-linearity = 0.028). Similar results were found when serum cotinine (log2 transformation) was used as a continuous variable [OR = 1.02 (1.01-1.03), P < 0.001] or complete data was used to analyze after MI. In the MR analysis, genetically predicted high serum cotinine was causally related to the high risk of nephrolithiasis [IVW: OR = 1.09 (1.00-1.19), P = 0.044]. Conclusion: Current smoking and high serum cotinine concentrations may be associated with an increased risk of kidney stones. Further research is needed to validate this relationship and explore its underlying mechanisms.

18.
Front Oncol ; 13: 1322078, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38293701

RESUMO

Deregulation of cell cycles can result in a variety of cancers, including breast cancer (BC). In fact, abnormal regulation of cell cycle pathways is often observed in breast cancer, leading to malignant cell proliferation. CDK4/6 inhibitors (CDK4/6i) can block the G1 cell cycle through the cyclin D-cyclin dependent kinase 4/6-inhibitor of CDK4-retinoblastoma (cyclinD-CDK4/6-INK4-RB) pathway, thus blocking the proliferation of invasive cells, showing great therapeutic potential to inhibit the spread of BC. So far, three FDA-approved drugs have been shown to be effective in the management of advanced hormone receptor positive (HR+) BC: palbociclib, abemaciclib, and ribociclib. The combination strategy of CDK4/6i and endocrine therapy (ET) has become the standard therapeutic regimen and is increasingly applied to advanced BC patients. The present study aims to clarify whether CDK4/6i can also achieve a certain therapeutic effect on Human epidermal growth factor receptor 2 positive (HER2+) BC. Studies of CDK4/6i are not limited to patients with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) advanced BC, but have also expanded to other types of BC. Several pre-clinical and clinical trials have demonstrated the potential of CDK4/6i in treating HER2+ BC. Therefore, this review summarizes the current knowledge and recent findings on the use of CDK4/6i in this type of BC, and provides ideas for the discovery of new treatment modalities.

19.
Chem Commun (Camb) ; 58(16): 2730-2733, 2022 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-35113981

RESUMO

A simple Ni(II)-catalyzed C-H hydroarylation of diarylacetylenes with imidazolium salts without adding any ligand was developed. It provides a facile and efficient access to (E)-2-(1,2-diarylvinyl)imidazolium salts. The preliminary results indicate a rare nonredox catalytic cycle of Ni(II), complementary to the common redox catalytic cycle starting from Ni(0).

20.
Int J Gen Med ; 15: 5701-5713, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35755862

RESUMO

Background: Tumor immune cell infiltration is closely associated with the occurrence and development of tumors. Collagen triple helix repeats containing 1 (CTHRC1), a regulator of collagen expression and cell migration, is involved in the metastasis and invasion of tumors. However, the role of CTHRC1 in breast cancer remains unclear. This study aimed to investigate the prognostic value of CTHRC1, and further explore its association with immune infiltration in breast cancer. Methods: CTHRC1 expression pattern and prognostic value were analyzed using ONCOMINE, PrognoScan, GEPIA, and Kaplan-Meier Plotter databases. We then detected CTHRC1 mRNA levels in breast cancer tissues and paired normal breast tissues by Q-PCR. Subsequently, the University of California Santa Cruz (UCSC) database was used to determine the methylation status of CTHRC1. Furthermore, CTHRC1 mutations were investigated using the Catalogue of Somatic mutations in Cancer (COSMIC) and cBioPortal databases. We also assessed the correlation between CTHRC1 expression and immune cell infiltration using TIMER. In addition, The relationship of CTHRC1 expression with the immune marker sets of various immune cells was evaluated using GEPIA and TIMER. Results: CTHRC1 was highly expressed in a variety of tumors, including breast cancer. Elevated CTHRC1 expression was related to a poor prognosis. Notably, CTHRC1 expression was significantly associated with macrophage infiltration, especially the immune infiltration gene marker set of M2. Copy number variations, DNA mutations and methylation states might be potential mechanisms for regulating CTHRC1 expression. Protein digestion and absorption, human papillomavirus infection, ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling pathways were identified as the potential CTHRC1-driven signaling pathways. Conclusion: These findings suggest that CTHRC1 could be a promising immune-related biomarker for the treatment of breast cancer patients.

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