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1.
Front Pharmacol ; 12: 665951, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239440

RESUMO

Purpose: The objective of this study was to evaluate the efficacy of machine learning algorithms in predicting risks of complications and poor glycemic control in nonadherent type 2 diabetes (T2D). Materials and Methods: This study was a real-world study of the complications and blood glucose prognosis of nonadherent T2D patients. Data of inpatients in Sichuan Provincial People's Hospital from January 2010 to December 2015 were collected. The T2D patients who had neither been monitored for glycosylated hemoglobin A nor had changed their hyperglycemia treatment regimens within the last 12 months were the object of this study. Seven types of machine learning algorithms were used to develop 18 prediction models. The predictive performance was mainly assessed using the area under the curve of the testing set. Results: Of 800 T2D patients, 165 (20.6%) met the inclusion criteria, of which 129 (78.2%) had poor glycemic control (defined as glycosylated hemoglobin A ≥7%). The highest area under the curves of the testing set for diabetic nephropathy, diabetic peripheral neuropathy, diabetic angiopathy, diabetic eye disease, and glycosylated hemoglobin A were 0.902 ± 0.040, 0.859 ± 0.050, 0.889 ± 0.059, 0.832 ± 0.086, and 0.825 ± 0.092, respectively. Conclusion: Both univariate analysis and machine learning methods reached the same conclusion. The duration of T2D and the duration of unadjusted hypoglycemic treatment were the key risk factors of diabetic complications, and the number of hypoglycemic drugs was the key risk factor of glycemic control of nonadherent T2D. This was the first study to use machine learning algorithms to explore the potential adverse outcomes of nonadherent T2D. The performances of the final prediction models we developed were acceptable; our prediction performances outperformed most other previous studies in most evaluation measures. Those models have potential clinical applicability in improving T2D care.

2.
Dalton Trans ; 50(32): 11130-11136, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34323902

RESUMO

A series of Bi3+ and Mn2+ co-doped CaZnOS phosphors with a tunable emission color have been synthesized by a high temperature solid-state reaction method. Their crystal structure, spectroscopic properties, energy transfer and thermal quenching have been investigated systematically. An intense blue-green emission band at 485 nm and a red emission band at 616 nm were observed at an excitation wavelength of 375 nm, owing to the 3P1,0→1S0 transition of Bi3+ and the 4T1(4G) →6A1(6S) transition of Mn2+, respectively. The tunable color from blue-green, white light to red light can be obtained by varying the Mn2+ ion concentration from 0.005 to 0.015 in CaZnOS:Bi3+. The decay time decreased from 642 to 273 ns with the Mn2+ ion concentration x increasing from 0.005 to 0.015, and the energy transfer efficiency ηT can reach up to 65% in the CaZnOS:Bi3+,0.015Mn2+ phosphor. As the temperature increases from 300 to 420 K, the emission intensity is maintained at 67%, and the activation energy Ea is estimated to be 0.28 eV. An LED fabricated using CaZnOS:Bi3+,0.01Mn2+ exhibited the chromaticity coordinates and corrected color temperature (CCT) of (0.338, 0.364) and 4655 K, respectively. These results validate the promising applications of the CaZnOS:Bi3+,Mn2+ phosphor in UV white LEDs.

3.
Food Chem ; 362: 130218, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34087713

RESUMO

In this research, three various Mw of chitosan (CS)-gallic acid (GA) conjugates were synthesized, characterized, and used for improvement of physicochemical stability of ß-carotene (BC) nanoemulsion (NE) by layer-by-layer technique. GA conjugation degrees were in the following order: HCS (125.6 mg/g) > MCS (102.3 mg/g) > LCS (74.6 mg/g) at GA:CS mass ratio of 0.5:1. Three varying Mw of CS-GA conjugates exhibited pronouncedly higher antioxidant abilities than native CS. For native CS, antioxidant abilities increased with the decrease of Mw. However, HCS-GA conjugate showed the highest antioxidant activity, due to the higher GA conjugation degrees and decreased intramolecular hydrogen bonds and crystallinity in HCS-GA conjugate. CS-GA conjugates substantially improved BC chemical stability in NE than CS and BC retentions were in the following order: HCS-GA (76.8%) > MCS-GA (68.3%) > LCS-GA (53.4%) after 30 days storage. The results obtained may provide some useful information for the applications of CS-GA conjugates for nutraceuticals stabilization in food systems.


Assuntos
Quitosana/química , Emulsões/química , Ácido Gálico/química , beta Caroteno/química , Antioxidantes/química , Suplementos Nutricionais , Armazenamento de Alimentos , Peso Molecular , Nanoestruturas/química , Eletricidade Estática
4.
Int J Endocrinol ; 2021: 8888862, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679975

RESUMO

Aims: To investigate the influence of body mass index (BMI) and its change from adolescence to adulthood (ΔBMI) on the risk of metabolic syndrome (MetS) in early adulthood. Methods: We selected 931 students from 12 to 16 years of age in Liaoyang City, China. Ninety-three participants from 18 to 22 years of age with complete baseline data were available for follow-up after 5 years. Statistical analysis determined the relationship of MetS at follow-up with baseline BMI (BMIb), ΔBMI, and follow-up BMI (BMIf). Results: ΔBMI was positively correlated with the change of waist circumference (ΔWC), systolic blood pressure (ΔSBP), triglycerides (ΔTG), uric acid, and glycosylated hemoglobin (ΔHbA1c) in follow-up (p < 0.05). For every 1 kg/m2 increase in BMIb, ΔBMI, and BMIf, the risk of MetS at follow-up increased 1.201-fold, 1.406-fold, and 1.579-fold, respectively. Both BMIb and ΔBMI were predictive of MetS at follow-up, with prediction thresholds of 23.47 kg/m2 and 1.95 kg/m2. The participants were divided by the predicted BMIb and ΔBMI threshold values into four study groups. Interestingly, the group with lower BMI but a higher increase in BMI presented the same metabolic derangements and Mets% of the group with higher BMI but lower Δ BMI. Conclusion: Both BMI of adolescence and ΔBMI were predictive of MetS and cardiovascular risk factors in adulthood. Control of both variables in adolescents would be more effective in decreasing the risk of MetS in young adults than control of BMI alone.

5.
Food Chem ; 348: 129102, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33508599

RESUMO

The present study aimed to fabricate whey protein isolate (WPI)-sodium alginate (ALG) nanocomplexes for curcumin (CUR) stabilization in a model fat-free beverage. Mass ratio of 5:1 at pH 5.0 in the absence of NaCl was optimized for WPI-ALG nanocomplex fabrication. Mean particle size and zeta-potential of CUR-WPI-ALG nanocomplex was 209.9 nm and -39.1 mV at pH 5.0, respectively. Highest loading amount (LA) of CUR in CUR-WPI-ALG nanocomplex were 15.26 µg/mg. No obvious precipitates were observed for CUR-WPI-ALG nanocomplex under simulated food processing and storage conditions including high sucrose, high NaCl, and thermal treatment at 90 °C for 2 h. Fluorescence results confirmed that the spontaneous interaction between CUR and WPI-ALG nanocomplex was primarily motivated by hydrophobic interaction and hydrogen bonding. Compared with CUR (free), chemical stability (UV light, and heat), and DPPH scavenging capacities of CUR in CUR-WPI-ALG nanocomplex were strikingly improved.


Assuntos
Alginatos/química , Bebidas/análise , Curcumina/química , Proteínas do Soro do Leite/química , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula , Solubilidade
6.
Appl Opt ; 59(24): 7477-7483, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32902517

RESUMO

A reconfigurable photonic binary phase-coded microwave signal generator with fundamental/subharmonic carrier frequency is proposed and experimentally investigated based on a dual-electrode dual parallel Mach-Zehnder modulator (DE-DPMZM). The local oscillator (LO) signal and coding signal are intensity modulated and phase modulated, respectively, on the two arms of the DE-DPMZM. The bias voltage of the intensity modulator is set to the quadrature or maximum working points to produce fundamental or subharmonic frequency, respectively. By precisely adjusting the amplitude of the LO signal and the bias voltage of the parent modulator, the light carriers of both arms of the DE-DPMZM can be eliminated. After detection, binary phase-coded microwave signal with frequency equal to or twice the frequency of the LO signal can be generated. The proposed system has a simple structure, high reconfigurability, and good frequency tunability due to its avoidance of using optical filters. In the experiment, phase-coded microwave waveforms at 6 GHz and 11 GHz are generated by using 6 GHz and 11 GHz LO signals or 3 GHz and 5.5 GHz LO signals, respectively. Meanwhile, the performance is evaluated in terms of phase recovery accuracy and pulse compression capability. The experimental results show that the proposed generator has high peak-to-sidelobe ratio, which has practical significance for radar detection of weak targets.

7.
Aging Cell ; 19(9): e13206, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32744417

RESUMO

Mammals' aging is correlated with the accumulation of somatic heteroplasmic mitochondrial DNA (mtDNA) mutations. Whether and how aging accumulated mtDNA mutations modulate fertility remains unknown. Here, we analyzed oocyte quality of young (≤30 years old) and elder (≥38 years old) female patients and show the elder group had lower blastocyst formation rate and more mtDNA point mutations in oocytes. To test the causal role of mtDNA point mutations on infertility, we used polymerase gamma (POLG) mutator mice. We show that mtDNA mutation levels inversely correlate with fertility, interestingly mainly affecting not male but female fertility. mtDNA mutations decrease female mice's fertility by reducing ovarian primordial and mature follicles. Mechanistically, accumulation of mtDNA mutations decreases fertility by impairing oocyte's NADH/NAD+ redox state, which could be rescued by nicotinamide mononucleotide treatment. For the first time, we answer the fundamental question of the causal effect of age-accumulated mtDNA mutations on fertility and its sex dependence, and show its distinct metabolic controlling mechanism.

8.
Elife ; 92020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32686646

RESUMO

Fertility across metazoa requires the germline-specific DAZ family of RNA-binding proteins. Here we examine whether DAZL directly regulates progenitor spermatogonia using a conditional genetic mouse model and in vivo biochemical approaches combined with chemical synchronization of spermatogenesis. We find that the absence of Dazl impairs both expansion and differentiation of the spermatogonial progenitor population. In undifferentiated spermatogonia, DAZL binds the 3' UTRs of ~2,500 protein-coding genes. Some targets are known regulators of spermatogonial proliferation and differentiation while others are broadly expressed, dosage-sensitive factors that control transcription and RNA metabolism. DAZL binds 3' UTR sites conserved across vertebrates at a UGUU(U/A) motif. By assessing ribosome occupancy in undifferentiated spermatogonia, we find that DAZL increases translation of its targets. In total, DAZL orchestrates a broad translational program that amplifies protein levels of key spermatogonial and gene regulatory factors to promote the expansion and differentiation of progenitor spermatogonia.


Assuntos
Diferenciação Celular , Proteínas de Ligação a RNA , Espermatogênese , Regiões 3' não Traduzidas , Animais , Diferenciação Celular/fisiologia , Masculino , Camundongos , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Espermatogênese/fisiologia , Espermatogônias/metabolismo
9.
Signal Transduct Target Ther ; 5(1): 82, 2020 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-32467564

RESUMO

Although targeted therapy has been extensively investigated for breast cancers, a molecular target with broad application is currently unavailable due to the high heterogeneity of these cancers. Mammaglobin-A (Mam-A), which is overexpressed in most breast carcinomas, has been proposed as a promising target. However, the lack of specific targeting moieties due to uncertain binding epitopes hampers further translational study. Here, seven potential epitopes of Mam-A were disclosed, and a unique epitope was then identified in most types of breast cancers, despite the genotypic heterogeneity. With phage display technology, the epitope was determined to be N-terminal amino acids 42-51 of Mam-A (N42-51). Then, the N42-51 epitope-specific monoclonal antibody, mAb785, was conjugated to poly lactic-co-glycolic acid (PLGA) nanoparticles loaded with therapeutic agents, thereby enhancing the drug uptake and therapeutic efficacy in different genotypes of breast cancers. The computer simulation of the N42-51 epitope and the mAb785 structures, as well as their interactions, further revealed the specific targeting mechanism of the mAb785-conjugated nanoparticles to breast cancers.

10.
Int J Biol Macromol ; 152: 189-198, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32105693

RESUMO

In this study, pea protein isolate (PPI) nanoparticles were fabricated with calcium-induced cross-linking and the potential as a nano-carrier for protecting resveratrol (RES) from degradation as well as improving its antioxidant activities was investigated. Ca2+ ions concentration and pH value had significant impacts on the formation of PPI nanoparticles. Dissociation assays suggested that PPI nanoparticles were mainly formed and stabilized by Ca2+ ions induced salt-bridge, hydrophobic interaction, and hydrogen bonding. Encapsulation efficiency (EE) and Loading amount (LA) of RES in PPI nanoparticles was 74.08%, and 30.24 µg/mg protein, respectively. Fluorescence emission results suggested that the formation of RES-PPI nanoparticles was primarily driven with hydrophobic interaction. AFM results clearly indicated that both RES-PPI nanocomplexes and RES-PPI nanoparticles were nano-scale, spherical shaped and distributed uniformly. RES-PPI nanoparticles exhibited higher physicochemical stability (Z-average diameter stability and RES retention) than RES-SPI nanocomplexes. Antioxidant ability of RES can be remarkably enhanced with both PPI-based nano-delivery systems. Ca2+ ions induced PPI nanoparticles obtained in this study have the great potential as functional delivery systems for hydrophobic nutraceuticals in food, and pharmaceutical industry.


Assuntos
Antioxidantes/química , Cálcio/química , Portadores de Fármacos/química , Nanopartículas/química , Proteínas de Ervilha/química , Resveratrol/química , Benzotiazóis/química , Compostos de Bifenilo/química , Tamanho da Partícula , Picratos/química , Solubilidade , Ácidos Sulfônicos/química
11.
Food Funct ; 11(2): 1740-1753, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32043514

RESUMO

The effects of essential hydrophobic carrier properties of α-lactalbumin (α-LA) : chitosan (CHI, Mw 100 kDa, degree of deacetylation 75-85%) including mass ratio and pH on the characteristics, emulsifying activities, and interfacial properties of α-LA-CHI complexes were investigated. The interaction between α-LA and CHI was dominated by electrostatic interactions. Soluble α-LA-CHI complexes can be formed at both pH 6.0, and 6.5 at mass ratios of 1 : 1, 2 : 1, and 5 : 1, as shown by their optical appearance. UV-vis spectra demonstrated that the interaction between α-LA and CHI is highly CHI concentration, and pH-dependent. AFM graphs confirmed that α-LA-CHI complexes were spherical in shape and homogeneously dispersed in solution. The diameters of α-LA-CHI complexes were found to be around 100-250 nm, which was in accordance with DLS results, even though some aggregates were observed for the 1 : 1 α-LA-CHI complex. The emulsifying activity of α-LA was enhanced by complexation with CHI. Both the emulsifying activity index (EAI) and emulsifying stability index (ESI) of α-LA-CHI complexes were associated with mass ratio and pH values. The interfacial tension of α-LA-CHI complexes was negatively exponentially correlated with the EAI. The lower the interfacial tension of α-LA-CHI complexes on the oil-water interface, the higher the EAI. The results obtained from this study were complementary and provided insights into the interaction between α-LA and CHI, and suggested that α-LA-CHI complexes can be utilized as effective food ingredients for stabilizing, protecting, and delivering hydrophobic nutraceuticals.


Assuntos
Quitosana/química , Coloides/química , Emulsões/química , Lactalbumina/química , Acetilação , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Nanoestruturas/química , Eletricidade Estática
12.
Food Funct ; 11(2): 1525-1536, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-31995080

RESUMO

Resveratrol (RES)-loaded protein-polysaccharide nanoparticles were fabricated through simple electrostatic interactions with oppositely charged α-lactalbumin (ALA) and chitosan (CHI) with a mass ratio of 5 : 1 without the addition of NaCl at pH 6.5. The Z-average diameter and zeta-potential values of RES-ALA-CHI nanoparticles were 211.0 nm and 13.23 mV, respectively. Both TEM and AFM graphs confirmed that RES-ALA-CHI nanoparticles had a spherical shape, and were dispersed homogeneously at the nanoscale. The encapsulation efficiency (EE) and loading amount (LA) of RES in RES-ALA-CHI nanoparticles were 58.86% and 196.2 µg mg-1, respectively, in the presence of 400 µg mL-1 RES. XRD results confirmed that RES was in amorphous form in ALA-CHI nanoparticles. The interaction between RES and ALA-CHI nanoparticles was mainly driven by hydrophobic interaction and hydrogen bonding. Compared to RES (free), the UV light and heat stability, in vitro bioaccessibility, and antioxidant activity of RES in RES-ALA-CHI nanoparticles were pronouncedly enhanced. The information provided in this study should be of interest to the food industry to fabricate robust nanoscale delivery systems with ALA-CHI nanoparticles for RES and other hydrophobic bioactive compounds.


Assuntos
Antioxidantes , Quitosana/química , Lactalbumina/química , Nanopartículas/química , Resveratrol , Antioxidantes/química , Antioxidantes/metabolismo , Compostos de Bifenilo/química , Compostos de Bifenilo/metabolismo , Portadores de Fármacos/química , Estabilidade de Medicamentos , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula , Picratos/química , Picratos/metabolismo , Resveratrol/química , Resveratrol/metabolismo
13.
Food Chem ; 313: 126118, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31945700

RESUMO

There is an ever-increasing need to protect health-beneficial ß-carotene (BC) from degradation with novel ingredients. Natural antioxidant-loaded protein-polysaccharide ternary complex has great potential for BC emulsions stabilization. In this study, curcumin (CUR)-loaded pea protein isolate (PPI), and high methoxyl pectin (HMP) ternary complex (804.0 nm) was fabricated by a self-assembly approach for BC emulsions stabilization. Highest CUR loading amount (LA, 33.19 µg/mg) was obtained in CUR-PPI-HMP complex. Hydrophobic interaction and hydrogen bonding were the prime driving forces for ternary complex formation. XRD results showed that CUR was amorphous. BC emulsion with PPI-HMP and CUR-PPI-HMP possessed higher droplet sizes (357.8 and 360.2 nm) than that with PPI and CUR-PPI (325.6, and 313.5 nm). Excellent physical stability with PPI-HMP and CUR-PPI-HMP was observed. BC retention with CUR-PPI-HMP was highest exposure to UV light (76.15%, 8 h), or heat treatment at 25 (91.50%) and 50 °C (74.35%) for 30 days.


Assuntos
Curcumina/química , Emulsões/química , Proteínas de Ervilha/química , Pectinas/química , beta Caroteno/química , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula , Temperatura , Raios Ultravioleta
14.
Food Funct ; 11(1): 768-778, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31917381

RESUMO

Whey protein isolate (WPI) nanoparticles were fabricated with Ca2+ induced cross-linking and used as an effective particle stabilizer for high internal phase Pickering emulsion (HIPPE) formulation aiming to improve the chemical stability and bioaccessibility of ß-carotene (BC). Ca2+ concentration dominated the characteristics of WPI nanoparticles. Spherically shaped and homogeneously dispersed WPI nanoparticles with a Z-average diameter of approximately 150.0 nm were obtained with 5.0 mM Ca2+ concentration. No cytotoxicity was observed for WPI nanoparticles even at 10.0 mg mL-1 concentration. HIPPE (oil fraction 80.0%, w/w) can be successfully prepared with WPI nanoparticles at a concentration as low as 0.2% (w/w) and was stable for at least 2 months at room temperature. A higher WPI nanoparticle concentration resulted in more solid-like HIPPEs. BC exhibited appreciably higher retention in HIPPEs than in bulk oil during 30 days of storage at 50 °C. Moreover, BC bioaccessibility was appreciably improved with the HIPPE delivery system. Both the chemical stability and bioaccessibility of BC increased with the increase of WPI nanoparticle concentrations from 0.2 to 1.0% (w/w). The results obtained in this study may facilitate the fabrication of edible and biocompatible protein-based nanoparticle stabilizers for HIPPE formulation with more innovative and tailored functionalities.


Assuntos
Proteínas do Soro do Leite/química , beta Caroteno/química , Cálcio/química , Fenômenos Fisiológicos do Sistema Digestório/efeitos dos fármacos , Armazenamento de Medicamentos , Emulsões/química , Humanos , Nanopartículas , beta Caroteno/farmacocinética
15.
J Assist Reprod Genet ; 37(2): 297-304, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31867688

RESUMO

PURPOSE: To determine age-adjusted overall success rates for patients undergoing clomiphene citrate only minimal stimulation cycle (mini) in vitro fertilization (IVF) without any gonadotropin administration. METHODS: Eight hundred thirty-nine women (mean age: 38.4 ± 0.1 years; 2488 cycles) underwent clomiphene citrate only mini-IVF. Their first oocyte retrieval was between January 2009 and December 2009, with follow-up until December 2014. The cumulative live birth rate (CLBR) per oocyte retrieval cycle started and live birth rate per oocyte was retrospectively analyzed. The basic CLBR was calculated as the number of women who achieved a live birth divided by the total number of women who started oocyte retrieval. RESULTS: The mean number of oocytes retrieved was 1.5. The basic CLBRs for all ages after the first and third cycles were 22.6% and 39.2%, respectively. For ≤ 34 years, 35-37 years, 38-40 years, 41-42 years, and ≥ 43 years, CLBRs after the first and third cycles were 42.5% and 70.1%, 32.9% and 49.1%, 20.0% and 38.6%, 12.6% and 25.2%, and 4.4% and 8.8%, respectively. These rates had a significant relationship with age (P < 0.01). The LBR per oocyte for all ages was 9.6%. CONCLUSION: Acceptable overall IVF success rates can be achieved in clomiphene citrate only mini-IVF, as well as acceptable LBR. The CLBRs and LBRs per oocyte are evidently influenced by women's age.


Assuntos
Clomifeno/administração & dosagem , Fertilização In Vitro , Oócitos/crescimento & desenvolvimento , Adulto , Coeficiente de Natalidade , Transferência Embrionária/métodos , Feminino , Gonadotropinas/metabolismo , Humanos , Nascido Vivo/epidemiologia , Recuperação de Oócitos/métodos , Oócitos/efeitos dos fármacos , Indução da Ovulação/métodos , Gravidez , Taxa de Gravidez , Injeções de Esperma Intracitoplásmicas/métodos
16.
Liver Int ; 40(3): 598-608, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31758647

RESUMO

BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is a major cause of chronic liver disease. The precise role of NK cells in the progression of NASH has yet to be elucidated. METHODS: Using methionine- and choline-deficient diets (MCD)-induced NASH model, the role of NK cells was identified in WT mice compared with conventional NK cell-deficient Nfil3-/- mice. RESULTS: After 8 weeks of MCD treatment, NASH was induced as shown by the significant macrovesicular steatosis, necro-inflammation and fibrosis in the liver of WT B6 mice. In MCD-treated WT B6 mice, the number of NK cells was markedly increased in the liver, but decreased in the spleen. Intrahepatic NK cells exhibited high levels of activation, as evidenced by the expression of CD107a and cytokine production of IFN-γ, TGF-ß and IL-10. Lower expression levels of Ki67 indicated a reduction in the proliferation of intrahepatic NK cells after MCD treatment. Increased expression of CXCL10 in the liver early after MCD treatment led to the increased recruitment of CXCR3+ NK cells into the liver. The MCD-treated Nfil3-/- mice showed similar levels of TG and macrovesicular steatosis, thus more inflammatory infiltration and increased collagen deposition in the liver. Furthermore, the depletion of NK cells during MCD-induced NASH caused a significant increase in the infiltration of monocyte-derived macrophages (MoMFs) particularly Ly6Clo subsets towards M2. CONCLUSIONS: Intrahepatic NK cells, recruited through CXCL10-CXCR3 interaction, play a protective role against the fibrosis progression in NASH, which provide us with a better understanding of the immunopathogenesis of NASH.


Assuntos
Deficiência de Colina , Hepatopatia Gordurosa não Alcoólica , Animais , Deficiência de Colina/patologia , Fibrose , Células Matadoras Naturais , Fígado/patologia , Metionina , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/patologia
17.
Proc Natl Acad Sci U S A ; 116(51): 25677-25687, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31754036

RESUMO

Mammalian primordial germ cells (PGCs) are induced in the embryonic epiblast, before migrating to the nascent gonads. In fish, frogs, and birds, the germline segregates even earlier, through the action of maternally inherited germ plasm. Across vertebrates, migrating PGCs retain a broad developmental potential, regardless of whether they were induced or maternally segregated. In mammals, this potential is indicated by expression of pluripotency factors, and the ability to generate teratomas and pluripotent cell lines. How the germline loses this developmental potential remains unknown. Our genome-wide analyses of embryonic human and mouse germlines reveal a conserved transcriptional program, initiated in PGCs after gonadal colonization, that differentiates germ cells from their germline precursors and from somatic lineages. Through genetic studies in mice and pigs, we demonstrate that one such gonad-induced factor, the RNA-binding protein DAZL, is necessary in vivo to restrict the developmental potential of the germline; DAZL's absence prolongs expression of a Nanog pluripotency reporter, facilitates derivation of pluripotent cell lines, and causes spontaneous gonadal teratomas. Based on these observations in humans, mice, and pigs, we propose that germ cells are determined after gonadal colonization in mammals. We suggest that germ cell determination was induced late in embryogenesis-after organogenesis has begun-in the common ancestor of all vertebrates, as in modern mammals, where this transition is induced by somatic cells of the gonad. We suggest that failure of this process of germ cell determination likely accounts for the origin of human testis cancer.


Assuntos
Diferenciação Celular/genética , Embrião de Mamíferos , Regulação da Expressão Gênica no Desenvolvimento/genética , Células Germinativas , Gônadas , Animais , Embrião de Mamíferos/citologia , Embrião de Mamíferos/fisiologia , Feminino , Células Germinativas/metabolismo , Células Germinativas/fisiologia , Gônadas/citologia , Gônadas/fisiologia , Masculino , Camundongos , Neoplasias Ovarianas/genética , Células-Tronco Pluripotentes/metabolismo , Células-Tronco Pluripotentes/fisiologia , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Suínos , Teratoma/genética , Neoplasias Testiculares/genética
18.
Stem Cell Res ; 40: 101576, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31622877

RESUMO

We generated three human induced pluripotent stem cell (hiPSC) sublines from human dermal fibroblasts (HDFs) (MZT04) generated from a skin biopsy donated from a previously fertile woman. The skin biopsy was broadly consented for generating hiPSC lines for biomedical research, including unique consent specifically for studying human fertility, infertility and germ cells. hiPSCs were reprogrammed using Sendai virus vectors and were subsequently positive for markers of self-renewal including OCT4, NANOG, TRA-1-81 and SSEA-4. Pluripotency was further verified using teratomas and PluriTest. These sublines serve as controls for hiPSC research projects aimed at understanding the cell and molecular regulation of female fertility and infertility.


Assuntos
Linhagem Celular/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Diferenciação Celular , Linhagem Celular/metabolismo , Células Cultivadas , Reprogramação Celular , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Homozigoto , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Masculino , Pessoa de Meia-Idade , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo
19.
J Cancer ; 10(16): 3778-3788, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31333795

RESUMO

Selective covalent CDK7 inhibitor THZ1 is a promising potential anti-tumor drug in many kinds of cancers. Epithelial-mesenchymal Transition (EMT) is highly related to cancer initiation, development, invasion and metastasis and other pathogenesis processes. We treated cancer cell line Hela229 and three retinoblastoma cell lines so-RB50, WERI-Rb-1, Y79 with gradient concentration of THZ1, and found that THZ1 could inhibit cell viability and EMT, suggesting that THZ1 may be a promising drug for human cervical cancer and retinoblastoma treatment. Our results verified the role of THZ1 in EMT for the first time, however, the mechanism needs further study. Here we report that THZ1 suppresses the TGFß2 induced EMT in human SRA01/04 lens epithelial cells (LECs), rabbit primary lens epithelial cells, and whole rat lens culture semi-in vivo model. RNA-sequencing and KEGG analysis revealed that the THZ1 inhibits EMT by down-regulating phosphorylate Smad2 and Notch signaling pathway. On the other hand, we found that THZ1 could strongly inhibit LECs proliferation through G2/M phase arrest as well as attenuating of MAPK, PI3K/AKT signaling pathway. Our results uncovered the function and underlying mechanism of THZ1 in regulation of EMT, which provides a new perspective of the anti-tumor effect by THZ1 and may offer a novel treatment for PCO.

20.
Nanoscale ; 11(30): 14123-14133, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31322633

RESUMO

Quantum dots, derived from two-dimensional (2D) materials, have shown promise in bioimaging, sensing and photothermal applications, and in white light emitting devices (WLEDs). Herein, nitrogen and phosphorus functionalized Ti3C2 MXene based quantum dots (N,P-MQDs) were successfully prepared through a top-bottom hydrothermal method. This type of photoluminescent quantum dots has realized green fluorescence for the first time at around 560 nm with a photoluminescence quantum yield (PLQY) of 20.1%, the highest ever reported; meanwhile, it also exhibits excellent photostability and pH resistance capacities. Comprehensive characterization and well-resolved density functional theory (DFT) calculation were implemented to determine the mechanism of fluorescence shift and enhancement. Furthermore, the N,P-MQDs have been proved to efficiently act as fluorescent probes for macrophage labeling. In addition, the high sensitivity of the N,P-MQDs toward Cu2+ ions made them a low cost, sensitive, environment-friendly, and label-free fluorescence platform for Cu2+ detection. The outstanding performance of Ti3C2 MXene based quantum dots has demonstrated their great potential to be used as promising fluorescent probes in the fields of biological imaging, optical sensing, photoelectric conversion, etc.


Assuntos
Cobre/análise , Macrófagos/química , Microscopia de Fluorescência , Pontos Quânticos/química , Titânio/química , Linhagem Celular , Teoria da Densidade Funcional , Corantes Fluorescentes/química , Humanos , Concentração de Íons de Hidrogênio , Íons/química , Macrófagos/metabolismo , Espectrometria de Fluorescência
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