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1.
Chemosphere ; 361: 142462, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38815816

RESUMEN

As perfluorooctanoic acid (PFOA) alternatives, hexafluoropropylene oxide dimeric acid (HFPO-DA) and hexafluoropropylene oxide trimeric acid (HFPO-TA) have been increasingly used and caused considerable water pollution. However, their toxicities to aquatic organisms are still not well known. Therefore, in this study, zebrafish embryos were exposed to PFOA (0, 1.5, 3 and 6 mg/L), HFPO-DA (0, 3, 6 and 12 mg/L) and HFPO-TA (0, 1, 2 and 4 mg/L) to comparatively investigate their thyroid disrupting effects and the developmental toxicity. Results demonstrated that waterborne exposure to PFOA and its two alternatives decreased T4 contents, the heart rate and swirl-escape rate of zebrafish embryos/larvae. The transcription levels of genes related to thyroid hormone regulation (crh), biosynthesis (tpo and tg), function (trα and trß), transport (transthyretin, ttr), and metabolism (dio1, dio2 and ugt1ab), were differently altered after the exposures, which induced the thyroid disrupting effects and decreased the heart rate. In addition, the transcription levels of some genes related to the nervous system development were also significantly affected, which was associated with the thyroid disrupting effects and consequently affected the locomotor activity of zebrafish. Therefore, HFPO-DA and HFPO-TA could not be safe alternatives to PFOA. Further studies to uncover the underlying mechanisms of these adverse effects are warranted.

2.
Cancer Res ; 84(11): 1781-1798, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38507720

RESUMEN

Inflammatory breast cancer (IBC) is a highly aggressive subtype of breast cancer characterized by rapidly arising diffuse erythema and edema. Genomic studies have not identified consistent alterations and mechanisms that differentiate IBC from non-IBC tumors, suggesting that the microenvironment could be a potential driver of IBC phenotypes. Here, using single-cell RNA sequencing, multiplex staining, and serum analysis in patients with IBC, we identified enrichment of a subgroup of luminal progenitor (LP) cells containing high expression of the neurotropic cytokine pleiotrophin (PTN) in IBC tumors. PTN secreted by the LP cells promoted angiogenesis by directly interacting with the NRP1 receptor on endothelial tip cells located in both IBC tumors and the affected skin. NRP1 activation in tip cells led to recruitment of immature perivascular cells in the affected skin of IBC, which are correlated with increased angiogenesis and IBC metastasis. Together, these findings reveal a role for cross-talk between LPs, endothelial tip cells, and immature perivascular cells via PTN-NRP1 axis in the pathogenesis of IBC, which could lead to improved strategies for treating IBC. SIGNIFICANCE: Nonmalignant luminal progenitor cells expressing pleiotrophin promote angiogenesis by activating NRP1 and induce a prometastatic tumor microenvironment in inflammatory breast cancer, providing potential therapeutic targets for this aggressive breast cancer subtype.


Asunto(s)
Proteínas Portadoras , Citocinas , Neoplasias Inflamatorias de la Mama , Neovascularización Patológica , Microambiente Tumoral , Humanos , Femenino , Citocinas/metabolismo , Proteínas Portadoras/metabolismo , Proteínas Portadoras/genética , Animales , Ratones , Neovascularización Patológica/patología , Neovascularización Patológica/metabolismo , Neoplasias Inflamatorias de la Mama/patología , Neoplasias Inflamatorias de la Mama/metabolismo , Neoplasias Inflamatorias de la Mama/genética , Neuropilina-1/metabolismo , Neuropilina-1/genética , Línea Celular Tumoral , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/metabolismo , Metástasis de la Neoplasia , Angiogénesis
3.
Environ Sci Pollut Res Int ; 31(5): 6835-6846, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38153579

RESUMEN

A magnetic composite of CoFe2O4 and carbon nanotube (CNT) was prepared using the solvothermal approach and then employed for the activation of peroxydisulfate (PDS) to degrade reactive black 5 (RB5) and other organic pollutants. Characterization results of the composite catalyst revealed the successful loading of spherical CoFe2O4 particles on CNTs, possessing abundant porosity as well as magnetic separation capability. Under the degradation conditions of 0.2 g/L CoFe2O4-CNT dosage and 4 mM PDS dosage, the removal efficiencies of 10 mg/L RB5 and other pollutants were in the range of 94.5 to ~ 100%. The effects of pH, co-existing ions/humic acid, and water matrices as well as the reusability of the catalyst were also investigated in detail. Furthermore, the degradation mechanism and pathway were proposed based on quenching experiments, LC-MS analysis, and density functional theory (DFT) calculations, and the toxicity of the degradation products was evaluated in the quantitative structure-activity relationship approach.


Asunto(s)
Contaminantes Ambientales , Nanotubos de Carbono , Naftalenosulfonatos , Catálisis , Fenómenos Magnéticos
4.
Breast Care (Basel) ; 18(5): 390-398, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37901045

RESUMEN

Objective: Dyslipidemia can promote cell proliferation, malignant transformation, metastasis, and cancer recurrence. Moreover, it could also affect immune infiltration in the tumor microenvironment. Therefore, we aimed to explore the effects of lipid levels on tumor-infiltrating lymphocytes (TILs) and prognosis in patients with triple-negative breast cancer (TNBC). Methods: Samples from 222 patients with TNBC from July 2007 to December 2019 were obtained from the tissue specimen banks in 3 hospitals. The blood samples were used to detect the levels of lipid levels such as apolipoprotein B (Apo B), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C). The TILs in the 222 TNBC tissues were detected using hematoxylin and eosin (H&E) staining, and the relationship between the lipid levels, clinical characteristics, and prognosis was analyzed. Results: Among TNBC patients, the overall survival (OS) time and disease-free survival (DFS) time were lower in patients with high LDL-C levels than those with low LDL-C levels (p < 0.01, respectively). The DFS was shorter in patients with low stromal TIL (STIL) levels than those with moderate or high STIL levels (p = 0.023). Multifactor Cox regression analysis showed that LDL-C level, Apo B level, and lymphocyte-predominant breast cancer were independent risk factors for OS in TNBC patients. The number of positive lymph nodes, postoperative staging, and total amount of TILs were independent risk factors for DFS in TNBC patients. Conclusion: The LDL-C and STIL levels were correlated with survival and prognosis in patients with TNBC.

5.
Environ Toxicol Chem ; 42(11): 2490-2500, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37589400

RESUMEN

As a novel alternative to perfluorooctanoic acid (PFOA), hexafluoropropylene oxide trimer acid (HFPO-TA) has been widely used and has caused ubiquitous water pollution. However, its adverse effects on aquatic organisms are still not well known. In the present study, zebrafish at different life stages were exposed to 0, 5, 50, and 100 µg/L of HFPO-TA for 21 days to investigate reproductive toxicity in zebrafish. The results showed that HFPO-TA exposure significantly inhibited growth and induced reproductive toxicity in zebrafish, including a decrease of the condition factor, gonadosomatic index, and the average number of eggs. Histological section observation revealed that percentages of mature oocytes and spermatozoa were reduced, while those of primary oocytes and spermatocytes increased. In addition, exposure to HFPO-TA at three stages induced a significant decrease in the hatching rate, while the heart rate and normal growth rate of F1 offspring were only significantly inhibited for the exposure from fertilization to 21 days postfertilization (dpf). Compared with the exposure from 42 to 63 dpf, the reproductive toxicity induced by HFPO-TA was more significant for the exposure from fertilization to 21 dpf and from 21 to 42 dpf. Expression of the genes for cytochrome P450 A1A, vitellogenin 1, estrogen receptor alpha, and estrogen receptor 2b was significantly up-regulated in most cases after exposure to HFPO-TA, suggesting that HFPO-TA exhibited an estrogen effect similar to PFOA. Therefore, HFPO-TA might disturb the balance of sex steroid hormones and consequently induce reproductive toxicity in zebrafish. Taken together, the results demonstrate that exposure to HFPO-TA at different life stages could induce reproductive toxicity in zebrafish. However, the underlying mechanisms deserve further investigation. Environ Toxicol Chem 2023;42:2490-2500. © 2023 SETAC.


Asunto(s)
Fluorocarburos , Pez Cebra , Masculino , Animales , Pez Cebra/fisiología , Reproducción , Fluorocarburos/toxicidad , Estrógenos
6.
Head Neck ; 45(4): 900-912, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36786387

RESUMEN

BACKGROUND: Enhancer RNAs (eRNAs) are increasingly recognized as prognostic biomarkers-across human cancers. Here, we sought to develop a novel eRNA-regulated genes (ERGs)-derived prognostic signature for head neck squamous cell carcinoma (HNSCC). METHODS: Candidate ERGs were identified via co-expression between individual survival-related eRNAs and their putative targets by Spearman's correlation analyses. The ERG signature was developed by univariate Cox regression, Kaplan-Meier survival analysis and maximum AUC in 1000 iterations of LASSO-penalized multivariate Cox regression. An ERG nomogram incorporating ERG signature and selected clinicopathological parameters were constructed by multivariate Cox regression. Biological roles of eRNA of interest were further explored in vitro. RESULTS: The ERG signature successfully stratified patients into subgroups with distinct survival in multiple cohorts. An ERG nomogram was developed with satisfactory performance in prognostication. Inhibition of ENSR00000165816 significantly reduced transcript level of SLC2A9 and impaired cell proliferation and invasion. CONCLUSION: Our results establish ERG signature and nomogram as powerful prognostic predictors for HNSCC.


Asunto(s)
Neoplasias de Cabeza y Cuello , ARN Largo no Codificante , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Pronóstico , Neoplasias de Cabeza y Cuello/genética , Nomogramas , ARN Largo no Codificante/genética , Proteínas Facilitadoras del Transporte de la Glucosa
7.
Oral Dis ; 2022 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-36398480

RESUMEN

BACKGROUND: Identifying cell subpopulations conferring unfavorable prognosis in cancer holds clinical significance. Here, we sought to identify prognostic cell subsets and develop a novel, prognostic signature for head neck squamous cell carcinoma (HNSCC). METHODS: Highly prognostic cell subpopulations in HNSCC were identified by integrating single-cell and bulk transcriptomic datasets. The prognostic signature and nomogram were developed by least absolute shrinkage and selection operator and multivariate Cox regression analyses based on significantly upregulated genes in this specific cell subpopulation, respectively. The qRT-PCR experiments were utilized for independent validation in our patient cohort. RESULTS: A specific cancer cell subset associated with unfavorable prognoses was identified. Functional dissections revealed that its transcriptional programs were significantly enriched in E2F, epithelial-to-mesenchymal transition, and glycolysis. A novel prognostic signature comprising six genes was developed and further validated. Risk scores based on qRT-PCR data robustly stratified patients into subgroups with distinct prognoses. A nomogram integrated from this signature and clinical stage had superior performance. CONCLUSION: Our model derived from integrative analyses of single-cell and bulk RNA-sequencing is a novel, robust prognostic biomarker for HNSCC.

8.
Water Sci Technol ; 86(10): 2611-2626, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36450676

RESUMEN

The magnetic composite of Fe3O4 and carbon nanotube (MCNT) was fabricated in a facile one-pot solvothermal method and employed to activate peroxydisulfate (PDS) for degradation of Rhodamine B (RhB) and other pollutants. The effects of operational factors including MCNT dosage and PDS dosage were studied, and high removal efficiencies of 84.2-99.5% were achieved for these pollutants with 0.3 g/L MCNT and 4 mM PDS. The effects of environmental factors including initial pH, inorganic cations, inorganic anions, humic acid and water matrix were also studied. Reusability test showed that the removal efficiency declined in four consecutive runs, which was attributed to the adsorbed oxidation products on the catalyst surface. Based on quenching experiments, solvent exchange (H2O to D2O), inductively coupled plasma and open circuit potential tests, it was concluded that radicals of ·OH/SO4·- and the non-radical electron-transfer pathway were involved in the MCNT/PDS system, and the contributions of O2·-, 1O2, high-valent iron-oxo species and homogenous activation were insignificant. Moreover, the orbital-weighted Fukui functions of RhB were calculated by density functional theory, and its plausible degradation pathway was proposed based on the calculation results. Finally, toxicity evaluation of the degradation products was performed in the quantitative structure-activity relationship approach.


Asunto(s)
Contaminantes Ambientales , Nanotubos de Carbono , Solventes , Agua , Fenómenos Magnéticos
9.
Chemosphere ; 309(Pt 1): 136608, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36183880

RESUMEN

In this study, generalized predictive models were developed to estimate KOA of four kinds of aromatic pollutants based on the calculated solvation free energy and taking the dimer effect into account. Uncorrected log KOA values, which were directly estimated from the calculated solvation free energy of individual molecules, underestimated experimental values, and the deviation increased with increasing log KOA. Dimers were found to greatly affect the apparent KOA values of these aromatic pollutants, which were driven by π-π interactions. London dispersion and exchange-repulsion terms were identified to be dominant components of the underlying π-π interactions. It is interesting to find that the π-π interactions of polybrominated diphenyl ethers correlate with not only the molecular polarizability but also the size of opposing aromatic surfaces, which leads to a different trend of π-π interactions from other aromatic pollutants. A universal quantitative structure-activity relationship model was developed to estimate the proportion of dimers based on five molecular structural descriptors relevant to the π-π interactions. After calibration with the dimer effect, estimations of log KOA were consistent with experimental values. Therefore, the dimer effect should be taken into consideration when investigating the partition behavior of aromatic pollutants, and the solvation free energy model could be an alternative method for the prediction of KOA.


Asunto(s)
Contaminantes Ambientales , Contaminantes Ambientales/análisis , Éteres Difenilos Halogenados , Temperatura , Octanoles/química , Relación Estructura-Actividad Cuantitativa , Polímeros , Agua/química
10.
Open Life Sci ; 17(1): 1217-1222, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36185401

RESUMEN

Reactivation of latent human herpesvirus 2 (HHV-2) can cause spontaneous recovering aseptic meningitis and recurrent meningitis in adults, but it rarely affects the brain parenchyma to cause encephalitis. Here, we report the case of a 37-year-old male patient admitted to our hospital due to fever with a progressive headache for 3 days and paroxysmal episodes of unconsciousness for 1 day. Brain magnetic resonance imaging (MRI) revealed viral meningoencephalitis. Then, metagenomics next-generation sequencing (mNGS) was applied, which detected 12,024 unique sequences of HHV-2 in cerebrospinal fluid (2022), indicating HHV-2 encephalitis. After antiviral treatment, the patient's symptoms improved, and he was discharged. During the 1-month follow-up, the patient recovered without any new symptoms, but a brain MRI revealed significant atrophy of the original foci. The patient was finally diagnosed with HHV-2 necrotizing meningoencephalitis, which is extremely rare. mNGS helped with the clinical diagnosis and strengthened our understanding of HHV-2 infections in the central nervous system.

11.
Opt Express ; 30(16): 28550-28558, 2022 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-36299047

RESUMEN

Ultra-broadband near-infrared (NIR) spectroscopy has unparalleled application prospects in intelligent detection and phosphor-converted light-emitting diodes (pc-LED), which are most likely to become the next generation of NIR light sources, has become a hot spot for research nowadays. To cope with the demand for more NIR spectroscopy applications, more efficient NIR phosphors need to be developed. Here, by screening the subject with a smaller band gap and by screening the suitable ion electronegativity of the lattice position where the Cr3+ is located, and then through the energy transfer, a series of Gd3Zn2GaGe2O12:xCr3+, yYb3+ (GZGG:Cr3+/Yb3+) NIR broadband garnet phosphors were found for the first time. By controlling the energy transfer process, the internal quantum yield (IQY) (54.9%), external quantum yield (EQY) (24.65%), bandwidth (260 nm), and thermal stability (60% at 150 °C) of NIR emission were substantially improved. The obtained phosphors are packaged with blue light chips into pc-LED, which can be applied in different fields such as vascular visualization and night vision.

12.
Front Microbiol ; 13: 935072, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36060753

RESUMEN

Bacillus halotolerans DS5 was isolated and identified as a halophilic microbe according to 16S rRNA analysis and the physical and chemical indices of the strain. A new alkaline protease (designated as prot DS5) from Bacillus halotolerans DS5 was produced, purified, and characterized. After 12 h incubation in the medium with 1% dextrin, 0.5% NaCl, 2% soluble starch, and 1% yeast extract (pH 7.0), it could reach the maximum enzyme activity (279.74 U/ml). The prot DS5 was stable in the pH range of 6.0-12.0 and the temperature range of 40-60°C, with maximal hydrolytic activities at pH 9 and at 50°C. In the presence of Ca2+, Mn2+, Ba2+, Mg2+, and Fe3+, protease activity was enhanced. The prot DS5 was maintained highly stable in NaCl (up to 2.5 mol/L), reducing and oxidizing agents. The prot DS5 also exhibited compatibility in other detergent ingredients, such as non-ionic and anionic surfactants. These properties of prot DS5 make this enzyme suitable for various industrial applications (e.g., detergents and leather).

13.
Math Biosci Eng ; 19(11): 10741-10761, 2022 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-36124568

RESUMEN

In this paper, considering that sometimes signal transmission may be interrupted, or signal input errors may occur, we establish a novel class of parametric uncertainty hybrid control system models including the impulsive control signals under saturated inputs, which can reflect the signal transmission process more realistically. Based on the step-function method, improved polytopic representation approach and Schur complement, we find the stability conditions, which are less conservative than those with the traditional Lyapunov method, of the considered control system. In addition, we investigate the design of the control gains and the auxiliary control gains for easily finding the suitable control signals, the auxiliary signals and the estimation of the attraction domain. Moreover, our proposed methods are applied to the fixed time impulse problems of uncertain systems with or without Zeno behavior. Simulation results for the uncertain neural network systems are presented to show the feasibility and effectiveness of our stabilization methods using the step-function.

14.
RSC Adv ; 12(33): 21026-21040, 2022 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-35919837

RESUMEN

Magnetic graphene oxide (MGO) was prepared and used as a catalyst to activate peroxymonosulfate (PMS) for degradation of Coomassie brilliant blue G250 (CBB). The effects of operation conditions including MGO dosage, PMS dosage and initial concentration of CBB were studied. CBB removal could reach 99.5% under optimum conditions, and high removals of 98.4-99.9% were also achieved for other organic dyes with varied structures, verifying the high efficiency and wide applicability of the MGO/PMS catalytic system. The effects of environmental factors including solution pH, inorganic ions and water matrices were also investigated. Reusability test showed that CBB removals maintained above 90% in five consecutive runs, indicating the acceptable recyclability of MGO. Based on quenching experiments, solvent exchange (H2O to D2O) and in situ open circuit potential (OCP) test, it was found that ˙OH, SO4˙- and high-valent iron species were responsible for the efficient degradation of CBB in the MGO/PMS system, while the contributions of O2˙-, 1O2 and the non-radical electron-transfer pathway were limited. Furthermore, the plausible degradation pathway of CBB was proposed based on density functional theory (DFT) calculations and liquid chromatography-mass spectrometry (LC-MS) results, and toxicity variation in the degradation process was evaluated by computerized structure-activity relationships (SARs) using green algae, daphnia, and fish as indicator species.

15.
Inorg Chem ; 61(29): 11284-11292, 2022 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-35834349

RESUMEN

Broadband near-infrared (NIR) phosphors are necessary materials for developing portable NIR light sources. Moreover, exploiting an NIR phosphor with a main peak located beyond a wavelength of 900 nm remains a challenge because this spectral range has great potential in biological nondestructive testing and solution testing. In this study, a range of Cr3+-doped ZnTa2O6 (ZTO) phosphors were completely synthesized by a solid-state method, which show broadband Cr3+ emission centered at 935 nm with a large full width at half maximum (FWHM) of 185 nm due to two distorted octahedral sites. A packaged phosphor-converted light-emitting diode (pc-LED) device is used to penetrate a 5-cm-thick chicken breast and identify diverse solutions based on differences in the measured transmission spectra. The results indicate broad application prospects in the field of biological tissue penetration and solution analysis.

16.
Chemosphere ; 306: 135628, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35810871

RESUMEN

In this study, a Ti3+-doped TiO2 porous membrane (Blue TiO2/Ti) was fabricated and employed for electrochemical degradation of organic pollutants in the single-pass flow-through mode. Characterizations including X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microcopy (SEM) and energy dispersive spectroscopy (EDS) verified that Ti3+-doped anatase TiO2 with nanotube structures was successfully prepared. Electrochemical analysis including linear sweep voltammetry (LSV), cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and electrochemical active surface area (ESA) revealed higher oxygen evolution potential (OEP, 2.23 V vs. Ag/AgCl), larger redox peak current, lower impedance and larger ESA (69 cm2/cm2) of Blue TiO2/Ti compared to the Ti and TiO2/Ti membranes. The effects of current density, flow rate and solution environment on the removal of methylene blue (MB) were investigated. The removal rates of various organic pollutants including sulfamethoxazole (SMX), methyl orange (MO), bisphenol A (BPA) and MB could reach 92.2%-99.5%. The quenching experiment proved that hydroxyl radicals (•OH) played the major role in the Blue TiO2/Ti based electrochemical system. Furthermore, the degradation pathways of two typical pollutants (SMX and MB) were proposed by analyzing the oxidation products with liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS), with the assistance of orbital-weighted Fukui index (fw0 and fw-) obtained through Density Functional Theory (DFT) calculations. Moreover, toxicity indexes of the oxidation products were obtained and compared to the parent SMX and MB using Toxicity Estimation Software Tool (TEST) software. Finally, the long-term operation performance of the Blue TiO2/Ti membrane was evaluated.


Asunto(s)
Contaminantes Ambientales , Nanotubos , Electrodos , Azul de Metileno , Nanotubos/química , Titanio/química
17.
Front Genet ; 13: 855355, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35480301

RESUMEN

Gastric cancer is a kind of gastrointestinal tumor with high morbidity and mortality. Finding effective methods for early diagnosis and treatment of gastric cancer has important significance and application prospects. MicroRNAs without protein coding potential affect the occurrence and development of gastric cancer. This study aims to explore the biological function and mechanism of microRNA-107 (miR-107) in gastric cancer. The results show that miR-107 is low expressed in gastric cancer, while TRIAP1 is highly expressed; the overexpression of miR-107 can inhibit the progression of gastric cancer in vivo and in vitro, while the overexpression plasmid of TRIAP1 can restore the miR-107 mimic-induced cell proliferation and metastasis inhibition, and the small interfering RNA of TRIAP1 can inhibit the cell proliferation and invasion induced by miR-107 inhibitor. In conclusion, the results of this study show that miR-107 can inhibit the proliferation of gastric cancer in vivo and in vitro by targeting TRIAP1.

18.
Int J Biol Macromol ; 209(Pt A): 1271-1279, 2022 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-35460754

RESUMEN

Inhibiting α-glucosidase activity is important in controlling postprandial hyperglycemia and, thus, helping to manage type-2 diabetes mellitus (T2DM). In the present study, we purified a hypothetical protein of carrots called DCHP (Daucus Carrot hypoglycemic peptide), and their inhibitory effects on α-glucosidase, as well as related mechanisms, were investigated. The recombinant DCHP protein with a molecular weight of 8 kDa showed strong inhibitory activity against α-glycosidase and maintained good stability in solution. DCHP exhibited no inhibitory activity but was tolerant to trypsin and chymotrypsin. Cellular experiments demonstrated that glucose consumption and lactic acid production increased rapidly when treated with DCHP in Caco-2 and HepG2 cells. DCHP crystal was generated, and the crystal structure, which was similar to that of rBTI and consisted of a central α-helix and a two-stranded ß-sheet with a unique loop region. The interaction between DCHP and α-glycosidase was investigated by molecular docking and site-directed mutation, which revealed that Glu43, Pro46, Thr47 Thr48 and Gln49 are the key residues in DCHP that inhibit α-glycosidase activity. This work provides potential bioactive peptides as functional foods or nutraceutical supplements in preventing and managing T2DM.


Asunto(s)
Daucus carota , Diabetes Mellitus Tipo 2 , Células CACO-2 , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/farmacología , Glicósido Hidrolasas , Humanos , Hipoglucemiantes/farmacología , Simulación del Acoplamiento Molecular , Péptido Hidrolasas , Inhibidores de Proteasas , alfa-Glucosidasas/metabolismo
19.
Mol Biol Rep ; 49(5): 3939-3947, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35449318

RESUMEN

BACKGROUND: Tamoxifen is a first-line endocrine agent and is often used to treat estrogen receptor-positive (ER+) breast cancer. Unfortunately, approximately 30-40% of patients who received tamoxifen therapy experience recurrence or progression to a fatal advanced stage due to tamoxifen resistance. However, the mechanisms of tamoxifen resistance remain unclear. METHODS: The expression of lncRNA DLGAP1 antisense RNA 2 (DLGAP1-AS2) was detected by qPCR. The effect of DLGAP1-AS2 on tamoxifen resistance was evaluated by MTT, colony formation, TUNEL and flow cytometric assays. The mechanisms by which DLGAP1-AS2 regulates tamoxifen resistance were investigated through qPCR, RNA pull-down assays and RNA immunoprecipitation (RIP) assays. RESULTS: Our results showed that DLGAP1-AS2 is significantly upregulated in breast cancer and that tamoxifen can induce DLGAP1-AS2 expression. Further investigation suggested that upregulation of DLGAP1-AS2 can increase cell viability and inhibit apoptosis, while downregulation of DLGAP1-AS2 results in the opposite effects. Mechanistically, DLGAP1-AS2 can bind to the AFF3 protein to inhibit its degradation, which further promotes ER signalling. CONCLUSIONS: Our research clarified that DLGAP1-AS2 promotes ER signalling to induce tamoxifen resistance and that targeting DLGAP1-AS2 might be a promising strategy to overcome tamoxifen resistance in breast cancer.


Asunto(s)
Neoplasias de la Mama , Resistencia a Antineoplásicos , ARN Largo no Codificante , Proteínas Asociadas a SAP90-PSD95/genética , Tamoxifeno/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , ARN sin Sentido/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo
20.
Inorg Chem ; 61(14): 5665-5671, 2022 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-35341247

RESUMEN

The exploration of efficient broadband near-infrared (NIR) emitting materials is essential to establishing new NIR applications. In this work, an excellent NIR phosphor Mg7Ga2GeO12:Cr3+, with an emission band of 650-1350 nm and a full width at half maximum of 266 nm, was successfully prepared. When Ga3+ ions were replaced by In3+ ions, its emission intensity increased 4 times, and the internal and external quantum efficiency reached 86 and 37%, respectively. A NIR phosphor-converted light-emitting diode (pc-LED) component was made by combining a synthetic Mg7Ga1.84In0.07GeO12:0.09Cr3+ phosphor with a 450 nm blue luminescent chip. The vascular and skeletal distribution on human fingers and the back of the hand can be seen under the display of a commercial NIR camera, indicating that Mg7Ga1.84In0.07GeO12:0.09Cr3+ phosphors have promising applications in the field of the blood vessel and bone visualization.


Asunto(s)
Cromo , Luminiscencia , Humanos , Ocupaciones
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