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1.
Nano Lett ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32031817

RESUMO

Photonic nanostructures that realize ultrafast switching of light polarization are essential to advancements in the area of optical information processing. The unprecedented flexibility of metasurfaces in light manipulation makes them a promising candidate for active polarization control. However, due to the lack of optical materials exhibiting a fast as well as large refractive index change, photonic metadevices capable of ultrafast polarization switching remain elusive. Here, an ultrathin nonlinear chiral meta-mirror consisting of an array of amorphous silicon (α-Si) split-ring resonators on top of a silver backplane is demonstrated as a feasible platform for picosecond all-optical polarization switching of near-infrared light at picojoule-per-resonator pump energies. This success was made possible by the high-quality-factor resonances of the proposed meta-atoms that enable the mirror to exhibit strong chiro- and enantioselectivity. Experimental results confirm that our meta-mirrors can be used to facilitate high-speed and power-efficient polarization-state modulators.

2.
Sex Transm Dis ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32011419

RESUMO

BACKGROUND: Partner notification (PN) is an essential component of syphilis control and is recommended by Chinese Sexually Transmitted Disease guidelines. However, in China, studies examining local practice are limited. This study evaluated partner notification outcomes among persons with early syphilis infection in an urban district in China. METHODS: From 2011 to 2017, persons diagnosed with early syphilis were asked to participate in an evaluation of supportive patient referral partner services for all recent sex partners, and the contact and case finding indices were determined in Nanshan District, Shenzhen, China. RESULTS: During the study period, 642 index patients with early syphilis reported 1749 sex partners. Of those partners, 678 were potentially contactable and 525 (30%) were contacted. The overall contact index was 0.82. Among the 1749 partners reported, 1108 (63%) were described as casual partners and only 37 (3%) were contacted (contact index 0.13) compared to 641 partners who were either spouses and regular partners (contact index 1.37). Among those 525 partners contacted, 418 (80%) were tested and 205 (39%) were diagnosed with and treated for syphilis. Among those, 9 (4%) were primary, 26 (13%) were secondary, 16 (8%) were early latent, and 154 (49%) were other syphilis infections. The overall case finding index was 0.29. CONCLUSIONS: There is a need to improve PN practices in China, which include developing operational guidelines of PN and to develop and evaluate novel PN ways like using Internet-based strategy.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32007626

RESUMO

Circular RNAs (circRNAs), covalently closed continuous RNA loops, are generated from cognate linear RNAs through back splicing events, and alternative splicing events may generate different circRNA isoforms at the same locus. However, the challenges of reconstruction and quantification of alternatively spliced full-length circRNAs remain unresolved. On the basis of the internal structural characteristics of circRNAs, we developed CircAST, a tool to assemble alternatively spliced circRNA transcripts and estimate their expression by using multiple splice graphs. Simulation studies showed that CircAST correctly assembled the full sequences of circRNAs with a sensitivity of 85.63%-94.32% and a precision of 81.96%-87.55%. By assigning reads to specific isoforms, CircAST quantified the expression of circRNA isoforms with correlation coefficients of 0.85-0.99 between theoretical and estimated values. We evaluated CircAST on an in-house mouse testis RNA-seq dataset with RNase R treatment for enriching circRNAs and identified 380 circRNAs with full-length sequences different from those of their corresponding cognate linear RNAs. RT-PCR and Sanger sequencing validated 32 out of 37 randomly selected isoforms, thus further indicating the good performance of CircAST, especially for isoforms with low abundance. We also applied CircAST to published experimental data and observed substantial diversity in circular transcripts across samples, thus suggesting that circRNA expression is highly regulated. CircAST can be accessed freely at https://github.com/xiaofengsong/CircAST.

5.
Int J Biochem Cell Biol ; 121: 105701, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32007602

RESUMO

As one of the major global health issues, allergic disease represents a considerable burden both on individual patients and public health. (-)-Asarinin (Asa), a lignan isolated from the roots of Asiasari radix, was reported to be associated with anti-allergic effect, but its efficacy and mechanism of action remain unclear. This study investigated the inhibitory effect of Asa on allergic reaction and its mechanism of action. Asa significantly suppressed Ag-sensitized human mast cell line LAD2 calcium mobilization, degranulation, and secretion. It also could reduce OVA-induced local and system anaphylaxis of mice in vivo. Further experiments revealed that Asa inhibit the mast cell activation by preventing the phosphorylation of Src family kinases. Moreover, after the IgE-dependent murine model of allergic rhinitis was treated with Asa, not only the concentration of histamine, total IgE, and IL-4 decreased, but also the inflammatory infiltrates and nasal mucosa incrassation were attenuated significantly. Meanwhile, Asa also inhibited the activation of mast cells induced by Compound48/80 in vivo and in vitro. In conclusion, Asa may serve as a potential novel Src family kinase inhibitor to inhibit IgE-dependent andIgE-independent allergic reaction and treat anaphylactic disease.

6.
Phytochemistry ; 172: 112282, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32036186

RESUMO

Seventeen highly oxygenated and rearranged limonoids, including nine previously undescribed phragmalin-type limonoids with 1,8,9- and 8,9,30-orthesters (entanutilins C-K, 1-9), three undescribed limonoids with rare rearranged-6/6/7/5 skeleton (entanutilins L-N, 10-12), and 5 known limonoids, were isolated from the stem barks of Entandrophragma utile from Ghana (Africa). Their structures including absolute configurations were elucidated based on comprehensive spectroscopic analyses, such as HRESIMS, 1D/2D-NMR, CD exciton chirality method, time-dependent density functional theory (TDDFT)/ECD calculations, and single-crystal X-ray diffraction. Bioactivity screenings suggested that some of these compounds effectively reversed resistance in MCF-7/DOX cells at a nontoxic concentration of 30 µM with 6- to 19-fold enhancing effects.

7.
Biomed Pharmacother ; 125: 109918, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32036213

RESUMO

OBJECTIVES: Drug abuse is one of the most severe global social and public health problems, especially in China. However, objective blood biomarkers that are easy to detect are still in great need. This study was aim to explore the expression pattern of circulating microRNAs (miRNAs) in subjects with drug addiction and test the potential of altered serum miRNAs as noninvasive diagnostic tools for drug abuse. METHODS: Serum samples were obtained from 42 heroin abusers, 42 methamphetamine (MA) abusers and 42 controls. Microarray-based miRNA analysis was first applied to screen unique serum miRNA profiles in drug abusers on a training set of serum samples from 12 heroin abusers, 12 MA abusers and 12 control subjects. The expression levels of selected candidate miRNAs were subsequently verified in individual samples of the training set and further confirmed independently in a validation set of samples from 30 heroin abusers, 30 MA abusers and 30 controls using real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: Microarray analysis identified 116 and 109 significantly altered miRNAs in heroin abusers and MA abusers, respectively. Three miRNAs, including let-7b-5p, miR-206 and miR-486-5p, were verified to be significantly and steadily increased in heroin abusers, and miR-9-3p was significantly increased in MA abusers compared with normal controls. The areas under the curve (AUCs) of the ROC curve of these miRNAs ranged from 0.718 to 0.867. CONCLUSIONS: Our study raises the possibility that the altered serum miRNAs could potentially be used as an auxiliary tool to identify individuals in drug abuse and addiction.

8.
Mar Pollut Bull ; 151: 110839, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32056629

RESUMO

Different phosphorus fractions, including total dissolved P (TDP), dissolved inorganic P (DIP), total particulate P (TPP), and particulate inorganic P (PIP), were analyzed in the Danshuei River Estuary (DRE), northern Taiwan to study the P partitioning within the estuary. Relatively higher concentrations of TDP (4.3-12.4 µM) and TPP (2.3-8.7 µM) were generally found in the upper estuary, salinity <5 region, during the four surveys. The DIP concentration generally dominated the total P pool (TDP + TPP) within the estuary. However, dissolved organic P (DOP) became the important fraction in the salinity >25 region, probably attributed to phytoplankton production because the higher DOP concentration was generally accompanied with a higher Chl. a concentration. The TPP concentrations generally correlated well with the total particulate Fe and Mn concentrations, suggesting that particulate Fe and Mn played crucial roles influencing the P distribution within the DRE.

9.
J Agric Food Chem ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32009392

RESUMO

Luteolin is a typical flavonoid and broadly distributed in the plants. Oral bioavailability of luteolin is low owing to extensive metabolism. Regioselective glucuronidation by UDP-glucuronosyltransferases (UGTs) and liver uptake by organic anion transporting polypeptides (OATPs) of luteolin and consequent glucuronidation metabolites were studied. Luteolin-3'-O-glucuronide (L-3'-G) and luteolin-7-O-glucuronide (L-7-G) were the major metabolites in human liver microsomes. Further study demonstrated that UGT1A9 played a predominant role in the glucuronidation of luteolin. Transporter study showed that OATP1B1- and 1B3-transfected cells selectively uptake L-3'-G into cells but not luteolin or L-7-G. After intravenous administration of luteolin to mice, the area under the curve of L-3'-G in the plasma was the highest among luteolin, L-3'-G, and L-7-G. In the liver, the concentration of L-3'-G was significantly greater than L-7-G. In conclusion, OATP1B1 and OATP1B3 play an important role in the liver disposition of luteolin and its glucuronidation metabolites.

10.
Ann Am Thorac Soc ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32011907

RESUMO

RATIONALE: Previous outcome studies of mechanical ventilation usually adopted a static time frame to observe the outcome and reported prognosis from the standpoint of the first ventilator day. However, patients and their family may repeatedly inquire about prognosis over time after the initiation of mechanical ventilation. OBJECTIVES: We aimed to describe dynamic changes in prognosis according to the elapsed time on ventilators for mechanically ventilated patients. METHODS: This cohort study used the entire population dataset of Taiwan's National Health Insurance database. We enrolled adults who newly received invasive mechanical ventilation for at least two consecutive days between March 1, 2010 and August 31, 2011. For every single ventilator day after the initiation of mechanical ventilation, we estimated the cumulative probabilities of weaning success and death in the following 90 days. RESULTS: A total of 162,200 episodes of respiratory failure requiring invasive mechanical ventilation were included. The median age was 72 years (IQR, 57-81) and the median follow-up time was 250 days (IQR, 30-463). The probability curve of weaning success against the time on ventilation showed a unidirectionally decreasing trend with a relatively sharp slope in the initial two months. The probabilities of weaning success in 90 days following the second, 7th, 21th and 60th ventilator days were 68.3% (95% CI, 68.1-68.5%), 62.6% (95% CI, 62.2-62.9%), 46.3% (95% CI, 45.8-46.8%) and 21.0% (95% CI, 20.3-21.8%), respectively. In contrast, the death curve has an initial increase and then a decreasing trend after the 19th ventilator day. We also reported tailored prognosis information according to the age, sex and ventilator-day of a mechanically ventilated patient. CONCLUSIONS: This study provides ventilator-day specific prognosis in a large cohort of unselected patients on invasive mechanical ventilation. The probability of weaning success decreases with the elapsed time on mechanical ventilation and the decline is particularly remarkable in the first two months of ventilatory support.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32013027

RESUMO

Remediation of soil heavy metal by biochar has been extensively studied. However, few studies focused on the role of biochar on the co-immobilization of cadmium (Cd(II)) and arsenate (As(V)) and related soil nutrient availability. Remediation tests were conducted with three types of pristine and ferric trichloride (FeCl3) modified biochar (rice, wheat, and corn straw biochar) in Cd-As co-contaminated soil, with application rates of 1, 5, and 10% (w/w) and the incubation of 1, 7, 10, and 15 days. Using TCLP (Toxicity Characteristic Leaching Procedure) method, 10% of FeCl3 modified corn-straw derived biochar (FCB) had the highest immobilization efficiency of Cd(II) (63.21%) and As(V) (95.10%) after 10 days of the incubation. Iron-modified biochar immobilized higher fractions of water-soluble (F1) and surface-absorbed (F2) metal fractions than pristine biochar. For FCB amendment, Cd was mostly presented in the organic matter (OM) and sulfides associated (F4) and residual (F5) fractions (88.52%), as was found in the Fe-Al (oxides and hydroxides) (F3), F4, and F5 fractions (75.87%). FCB amendment increased soil pH values and available iron contents (p < 0.05), while no changes in soil available phosphorus content (p > 0.05). This study showed that FCB application reduces the environmental mobility of metals in Cd-As contaminated soil, while it also increases soil pH and available nutrient mobility, improving soil environmental quality and reducing remediation costs.

12.
Head Neck ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32048783

RESUMO

Epithelial-mesenchymal transition (EMT) plays a critical role in cancer progression and is primarily regulated by several EMT-inducing transcription factors (EMT-TFs), including TWIST1, TWIST2, SNAI1, SNAI2, ZEB1, and ZEB2. However, the prognostic value of EMT-TFs remains controversial in head and neck squamous cell carcinoma (HNSCC). Studies on the prognostic role of EMT-TFs in HNSCC were searched for in the Web of Science, Science Direct, Proquest, EMBASE, PubMed, and Cochrane Library. Meta-analysis was performed by using Revman 5.2 software. The pooled analysis showed that overexpression of EMT-TFs indicated a poor overall survival (OS) (HR = 1.93, 95% CI = 1.67-2.23) of HNSCC. Subgroup analysis for individual EMT-TFs revealed that overexpression of TWIST1 (HR = 1.61, 95% CI = 1.29-2.02), SNAI1 (HR = 2.17, 95% CI = 1.63-2.88), SNAI2 (HR = 1.90, 95% CI = 1.38-2.62), and ZEB1 (HR = 2.70, 95% CI = 1.61-4.53) were significantly associated with poor OS of HNSCC. These findings support the hypothesis that overexpression of EMT-TFs indicates a poor prognosis for HNSCC patients.

13.
Clin Chem ; 66(2): 342-351, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32040577

RESUMO

BACKGROUND: Dysregulation of N6-methyladenosine (m6A) is associated with various human diseases including cancer. This study aimed to evaluate the level of m6A as a biomarker for gastric cancer (GC) diagnosis. METHODS: Peripheral blood samples were collected from 100 GC patients, 30 benign gastric disease (BGD) patients, and 75 healthy controls (HCs). Levels of m6A in total RNA and expression of m6A-related proteins were analyzed. RESULTS: The m6A levels in peripheral blood RNA were significantly increased in the GC group compared with those in the BGD or HC groups; moreover, levels increased with the progression and metastasis of GC and decreased in GC patients after surgery. The area under the curve (AUC) for m6A in the GC group was 0.929 (95% CI, 0.88-0.96), which is markedly greater than the AUCs for carcinoembryonic antigen (CEA; 0.694) and carbohydrate antigen 199 (CA199; 0.603). The combination of CEA and CA199 with m6A improved the AUC to 0.955 (95% CI, 0.91-0.98). The expressions of m6A demethylases ALKBH5 and FTO were significantly downregulated in the GC group compared with the HC group. Coculture with GC cells increased the m6A of RNA in promyelocytic (HL-60) and monocytic (THP-1) leukemia cells and nontumorigenic human peripheral blood B lymphocyte cells (PENG-EBV). Furthermore, a xenograft model enhanced the m6A in peripheral blood RNA of mice. Accordingly, expressions of ALKBH5 and FTO were decreased both in vitro and in vivo. CONCLUSIONS: Level of m6A in peripheral blood RNA is a promising noninvasive diagnostic biomarker for GC patients.

14.
J Am Chem Soc ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32050761

RESUMO

Rational construction of covalent organic frameworks (COFs) with novel structures still remains a challenge. Herein, we report-ed the designed synthesis of two COFs, 2D-BPTA-COF and 3D-BMTA-COF, starting from biphenyl-based precursors but with different groups on ortho positions. Both COFs exhibited high crystallinity and large surface area, and interestingly, 2D-BPTA-COF crystallizes into 2D sheets with AB stacking mode while 3D-BMTA-COF adopts a seven-fold interpenetrated structure with pts topology. This structural difference could be ascribed to the introduction of methyl groups in the building blocks, as the dihedral angle of biphenyl rings in 2D-BPTA-COF is ~0° while in 3D-BMTA-COF is ~60°. Therefore, it is possible to synthesize COFs with different structures by twisting building blocks from planar to tetrahedral with steric hindrance. We believe this result represents a general and straightforward way to expand the diver-sity of tetrahedral nodes for constructing 3D COFs in future, and moreover, a new tetrahedral node for constructing 3D COFs is now available.

15.
Psychon Bull Rev ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32052268

RESUMO

Human behavior fluctuates. A growing body of evidence has demonstrated that behavioral performance in perception fluctuates rhythmically, with dynamics closely resembling spectral features of neural oscillations. However, it is unclear whether the behavioral fluctuations in a complex cooperation context can also express similar rhythmic features, and, more importantly, whether these behavioral rhythms are synchronized among co-actors in a neurophysiologically relevant manner. To answer these questions, we applied a time-resolved approach, previously used for probing individual-level behavioral oscillations in perception, in a complex social interaction context, and further probed dyad-level behavioral synchrony. Twenty pairs of male participants completed, in dyad, joint-action tasks with cooperation or competition demand. We extracted behavioral rhythms from ongoing cooperative performance and measured behavioral synchrony by computing the phase coherence of these behavioral rhythms between dyad members. Despite the absence of significant behavioral oscillations in individuals' amplitude spectrum, we observed enhanced theta-band phase coherence between co-actors' behavioral rhythms during cooperation compared to competition conditions. These results indicate that cooperative behaviors of co-actors fluctuated synchronously within the theta band, providing a behavioral counterpart of theta-band interbrain synchrony in cooperation reported in previous hyperscanning studies. Furthermore, the observed behavioral synchrony could be used as a sensitive predictor of cooperation pattern, as evidenced by its significant correlation with leader-follower relationship during cooperation.

16.
J Pineal Res ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32052470

RESUMO

Melatonin (MT), endogenously secreted by the pineal gland, is closely related to multiple biological processes; however, its effect on thrombopoiesis is still not well illustrated. Here, we demonstrate that MT administration can elevate peripheral platelet levels. Analysis of different stages in thrombopoiesis reveals that MT has the capacity to promote the expansion of CD34+ and CD41+ cells, and accelerate proplatelet formation (PPF) and platelet production. Furthermore, in vivo experiments show that MT has a potential therapeutic effect on radiation-induced thrombocytopenia. The underlying mechanism suggests that both extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt signaling are involved in the processes of thrombopoiesis facilitated by MT. Interestingly, in addition to the direct regulation of Akt signaling by its upstream phosphoinositide 3-kinase (PI3K), ERK1/2 signaling is also regulated by PI3K via its effector, dual adaptor for phosphotyrosine and 3-phosphoinositides (DAPP1), in megakaryocytes after MT treatment. Moreover, the expression level of DAPP1 during megakaryocyte differentiation is closely related to the activation of ERK1/2 and Akt at different stages of thrombopoiesis. In conclusion, our data suggest that MT treatment can promote thrombopoiesis, which is modulated by the DAPP1-orchestrated activation of ERK1/2 and Akt signaling.

17.
Planta ; 251(2): 44, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907626

RESUMO

MAIN CONCLUSION: In Hordeum vulgare, nine differentially expressed novel miRNAs were induced by colchicine. Five novel miRNA in colchicine solution showed the opposite expression patterns as those in water. Colchicine is a commonly used agent for plant chromosome set doubling. MicroRNA-mediated responses to colchicine treatment in plants have not been characterized. Here, we characterized new microRNAs induced by colchicine treatment in Hordeum vulgare using high-throughput sequencing. Our results showed that 39 differentially expressed miRNAs were affected by water treatment, including 34 novel miRNAs and 5 known miRNAs; 42 miRNAs, including 37 novel miRNAs and 5 known miRNAs, were synergistically affected by colchicine and water, and 9 differentially expressed novel miRNAs were induced by colchicine. The novel_mir69, novel_mir57, novel_mir75, novel_mir38, and novel_mir56 in colchicine treatment showed the opposite expression patterns as those in water. By analyzing these 9 differentially expressed novel miRNAs and their targets, we found that novel_mir69, novel_mir56 and novel_mir25 co-target the genes involving the DNA repair pathway. Based on our results, microRNA-target regulation network under colchicine treatment was proposed, which involves actin, cell cycle regulation, cell wall synthesis, and the regulation of oxidative stress. Overall, the results demonstrated the critical role of microRNAs mediated responses to colchicine treatment in plants.

18.
FASEB J ; 34(1): 720-734, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914611

RESUMO

Confusion persists over pathogenesis of spondylolysis. To confirm pathogenicity of the previously identified causative mutation of spondylolysis and investigate the genetic etiology, we generate a new mouse line harboring D673V mutation in the Slc26a2 gene. D673V mutation induces delayed endochondral ossification characterized by transiently reduced chondrocyte proliferation in mice at the early postnatal stage. Adult D673V homozygotes exhibit dysplastic isthmus and reduced bone volume of the dorsal vertebra resembling the detached vertebral bony structure when spondylolysis occurs, including the postzygopophysis, vertebral arch, and spinous process, which causes biomechanical alterations around the isthmic region of L4-5 vertebrae indicated by finite element analysis. Consistently, partial ablation of Slc26a2 in vertebral skeletal cells using Col1a1-Cre; Slc26a2 fl/fl mouse line recapitulates a similar but worsened vertebral phenotype featured by lamellar isthmus. In addition, when reaching late adulthood, D673V homozygotes develop an evident bone-loss phenotype and show impaired osteogenesis. These findings support a multifactorial etiology, involving congenitally predisposed isthmic conditions, altered biomechanics, and age-dependent bone loss, which leads to SLC26A2-related spondylolysis.

19.
Theranostics ; 10(3): 1433-1453, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31938073

RESUMO

Elucidation of the molecular mechanisms governing aggressiveness of HNSCC may provide clinical therapeutic strategies for patients. In this study, a novel hub miR-204-5p functioning as tumor suppressor has been identified and explored in HNSCC. Methods: A novel hub miR-204-5p was identified based on miRNA microarray, bioinformatics analysis and validated in different HNSCC patient cohorts. The functional role of miR-204-5p and its downstream and upstream regulatory machinery were investigated by gain-of-function and loss-of-function assays in vitro and in vivo. Interactions among miR-204-5p and SNAI2/SUZ12/HDAC1/STAT3 complex were examined by a series of molecular biology experiments. Then, the clinical relevance of miR-204-5p and its targets were evaluated in HNSCC samples. HNSCC patient-derived xenograft (PDX) model was used to assess the therapeutic value of miR-204-5p. Results: We reveal that miR-204-5p as a tumor suppressor is commonly repressed in HNSCC, which can inhibit tumor growth, metastasis and stemness. Mechanically, miR-204-5p suppresses epithelial-mesenchymal transition (EMT) and STAT3 signaling by targeting SNAI2, SUZ12, HDAC1 and JAK2. Among these targets, we further showed that SNAI2, SUZ12, and HDAC1 form a repressive complex on CDH1 promoter to maintain EMT in HNSCC. In turn, the SNAI2/SUZ12/HDAC1 complex interacts with STAT3 on miR-204-5p-regulatory regions to suppress the transcription of miR-204-5p. Moreover, we also show that decrease of miR-204-5p indicates a poor prognosis in HNSCC patients and administration of agomiR-204-5p inhibits tumor growth and metastasis in HNSCC PDX models. Conclusion: miR-204-5p-SNAI2/SUZ12/HDAC1/STAT3 regulatory circuit has a critical role in maintaining aggressiveness of HNSCC, suggesting that miR-204-5p might serve as a promising therapeutic target for clinical intervention.

20.
FASEB J ; 34(2): 2792-2811, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31912559

RESUMO

While adipose tissue is required to maintain glucose metabolism, excessive calorie intake induces obesity via mechanisms including accelerated proliferation and differentiation of preadipocytes, leading to insulin resistance. Here, we investigated the role of myoferlin (MYOF), a ferlin family protein, in regulating glucose metabolism by mainly focusing on its unknown role in adipose tissue. Whereas young MYOF knockout (KO) mice on a normal diet showed aggravated glucose tolerance and insulin sensitivity, those on a high-fat diet (HFD) showed preserved glucose tolerance with an attenuated gain of body weight, reduced visceral fat deposits, and less severe fatty liver. The Adipose MYOF expression was reduced by aging but was restored by an HFD along with the retained expression of NFAT transcription factors. Loss-of-function of MYOF in preadipocytes suppressed proliferation and differentiation into mature adipocytes along with the decreased expression of genes involved in adipogenesis. The MYOF expression in preadipocytes was reduced with differentiation. Attenuated obesity in MYOF KO mice on an HFD was also accompanied with increased oxygen consumption by an unidentified mechanism and with reduced adipose inflammation due to less inflammatory macrophages. These insights suggest that the multifunctional roles of MYOF involve the regulation of preadipocyte function and affect glucose metabolism bidirectionally depending on consumed calories.

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