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1.
J Cell Physiol ; 235(1): 380-393, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31232476

RESUMO

Atherosclerosis (AS), a chronic disorder of large arteries, is the underlying pathological process of heart disease and stroke. Former researchers have found that microRNAs (miRs) are involved in the several key processes of AS. Apolipoprotein E knockout (ApoE-/- ) mice fed a high-fat-diet (HFD) to establish AS model. The expression of miR-103 was characterized in the mice model. The effects of miR-103 on inflammation and endoplasmic reticulum stress (ERS) were analyzed when the expression of miR-103 was inhibited in ApoE -/- mice fed an HFD and human aortic endothelial cells (HAECs) exposed to oxidized low-density lipoprotein (ox-LDL). The relationship between miR-103 and phosphatase and tensin homolog (PTEN) was identified by luciferase activity detection and real-time quantitative polymerase chain reaction (RT-qPCR). Gain- and loss-function approaches were further applied for investigating the regulatory effects of miR-103 and PTEN on ERS. Role of MAPK signaling was then analyzed using PD98059 to block this pathway. miR-103 was highly expressed in the ApoEApoE -/- mice fed an HFD. Downregulation of miR-103 suppressed inflammation and ERS in endothelial cells isolated from ApoE -/- mice fed a HFD and ox-LDL-exposed HAECs. In addition, miR-103 can target PTEN and downregulate its expression. Overexpression of PTEN reversed the miR-103-induced activation of MAPK signaling. Moreover, PTEN upregulation or MAPK signaling inhibition ease miR-103-induced inflammation and ERS in vivo and in vitro. Thus, miR-103 depletion restrains the progression of AS through blocking PTEN-mediated MAPK signaling.

2.
Nanotechnology ; 31(3): 035403, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31557753

RESUMO

The development of low-cost electrocatalysts with high performance is important to provide sustainable hydrogen energy. In this work, via one-step sulfuration of [Formula: see text] intercalated NiFe-layered double hydroxide (abbr. NiFe-MoO4-LDH), hierarchical microspheres are assembled by intersecting nanoplates (15-30 nm in thickness) which are then decorated with MoS2 and (NiFe)S x nanoparticles (∼25 nm in size). The NiFe-MoO4-LDH is synthesized beforehand by a one-pot hydrothermal reaction. Under sulfuration at 300 °C, 400 °C and 600 °C, the NiFe-MoO4-LDH transforms into multi-metal sulfides of NiFeMoS-T (T is applied temperature). During sulfuration, the confinement effect of LDH limits the growth of metal sulfides, causing formation of nanoparticles of MoS2 and (NiFe)S x to expose more catalytic active sites. In an alkaline medium, NiFeMoS-400 depicts superior performance for hydrogen evolution reaction (HER), giving an overpotential of 210 mV at 10 mA cm-2. A Tafel slope of 88 mV dec-1 indicates a mixed Volmer-Heyrovsky rate-determining step. The electrode also maintains long-term electrochemical durability during 15 h electrolysis at 25 mA cm-2. The NiFe-MoO4-LDH precursor owns three metal elements (Ni, Fe and Mo), which ensure the formation of polymetallic sulfides, and maximum utilization of the LDH layer and interlayer metals contributes to the optimal electrocatalytic activity. The NiFeMoS nanoassembly is a potential low-cost and high-efficiency electrocatalyst.

3.
J Hazard Mater ; 382: 121018, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31446354

RESUMO

The broad spectrum detection of veterinary drugs is very important for rapid and large-scale safe screen of animal-derived foods. Metal-organic frameworks (MOFs), as a kind of emerged functional porous materials are quite promising in the chemical sensing and molecular detection. In this work, we report the high-performance broad spectrum detection of 15 commonly-used veterinary drugs through the fluorescence quenching in a newly-designed chemically stable Al-based MOF, Al3(µ3-O)(OH)(H2O)2(PPTTA)3/2 (BUT-22). To the best of our knowledge, this is the first systematic investigation for the application of MOFs in the detection/sensing of veterinary drugs through fluorescence quenching method. The quenching efficiencies of the tested veterinary drugs on BUT-22 are all beyond 82%, and the limits of detection (LOD) are low at parts per billion (ppb) levels. Interestingly, BUT-22 also enables the selective detection of nicarbazin (NIC) through the clearly-observed red shift of its maximum fluorescence emission wavelength. Moreover, the fluorescence quenching mechanism was explored with the help of theoretical calculations. Our work indicates that MOFs are favorable materials for the detection of veterinary drugs, being potentially useful in monitoring drug residues of animal-derived foods.

4.
Res Microbiol ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31669369

RESUMO

Xanthomonas oryzae pv. oryzicola (Xoc) depends on its type III secretion system (T3SS) to translocate type III secreted effectors (T3SEs), including transcription activator-like effectors (TALEs) and non-transcription activator-like effectors (non-TALEs), into host cells. T3SEs can promote the colonization of Xoc and contribute to virulence by manipulating host cell physiology. We annotated 25 genes encoding non-TALEs in Xoc strain GX01, an isolate from Guangxi in the South China's rice growing region. Through systematic mutagenesis of non-TALEs, we found that xopN, the virulence contribution of which was previously unknown for Xoc, significantly contributes to the virulence of Xoc GX01, as does avrBs2.

5.
J Ethnopharmacol ; : 112338, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31669666

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Fritillariae cirrhosae (FC), referred to'Chuan beimu'in China. As an important edible and medicinal plant, the bulbs of F.cirrhosae is used traditionally in the treatment of pulmonary diseases associated with lung heat, inflammation and tumors. In the study, we investigated the effect of aqueous extract of FC (FC-AE) and elucidated its mechanism in non-small cell lung cancer A549 cells and a xenograft model of nude mice. MATERIALS AND METHODS: CCK-8 and plate colony formation assay were used to evaluate the effect of FC-AE in A549 cells in vitro, and the gene expression profile of FC-AE on A549 cells was assessed by RNA sequencing system. Then, the effects of FC-AE on cell cycle and apoptosis of A549 cells were analyzed by flow cytometry. In combination with RNA-seq data, RT-PCR and western blot were used to evaluate the expression of proteins related to apoptosis and immune regulation. A xenograft model of nude mice was used to assess the effect of FC-AE in vivo. RESULTS: CCK-8 and plate cloning assays showed that FC-AE inhibited the proliferation and colony formation of A549 cells. A549 cells treated with FC-AE can triggered apoptosis. GO and KEGG pathway enrichment analysis of RNA-seq data showed that most of the differentially expressed genes (DEGs) were related to immune response, apoptosis and cell cycle process. Several immune and apoptotic DEGs were identified by qRT-PCR which were consistented with RNA-seq data. In nude mice, FC-AE reduced the tumor size and promoted the secretion of cytokines IL12 and IFNγ. FC-AE up-regulated the two members (STAT1 and STAT4) of STATs and their target genes (IFNγ and IL-12, respectively) protein expressions, and actively regulates Bcl-2/Bax family proteins which resulted in cellular apoptosis in A549 cells. CONCLUSION: Our finding suggests that FC-AE mediates apoptosis through a STAT1 and STAT4-mediated co-regulatory network, which may be the key novel mechanism for its antitumor activity. The F. cirrhosa may be a promising antitumor drug for modulating immune responses to improve cancer therapy.

6.
Int J Med Sci ; 16(11): 1424-1429, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31673232

RESUMO

Down-regulation of Growth arrest-specific 5 (GAS5) is correlated with enhanced cell proliferation and poorer prognosis of prostate cancer. We aimed to investigate the effect of variant rs145204276 of GAS5 on the prostate cancer susceptibility and clinicopathologic characteristics. In this study, 579 prostate cancer patients who underwent robot-assisted radical prostatectomy and 579 healthy controls were included. The frequency of the allele del of rs145204276 were compared between the patients and the controls to evaluate the impact of tumor susceptibility and the correlation of clinicopathological variables. The results shown that patients who carries genotype ins/del or del/del at SNP rs145204276 showed decreased risk of pathological lymph node metastasis disease (OR=0.545, p=0.043) and risk of seminal vesicle invasion (OR=0.632, p=0.022) comparing to with genotype ins/ins. In the subgroup analysis of age, more significant risk reduction effects were noted over lymph node metastasis disease (OR=0.426, p=0.032) and lymphovascular invasion (OR=0.521, p=0.025). In conclusion, the rs145204276 polymorphic genotype of GAS5 can predict the risk of lymph node metastasis. This is the first study to report the correlation between GAS5 gene polymorphism and prostate cancer prognosis.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31666321

RESUMO

Secreted exosomal microRNAs (miRNAs) mediate interorgan/tissue communications by modulating target gene expression, thereby regulating developmental and physiological functions. However, the source, route, and function in target cells have not been formally established for specific miRNAs. Here, we show that glial miR-274 non-cell-autonomously modulates the growth of synaptic boutons and tracheal branches. Whereas the precursor form of miR-274 is expressed in glia, the mature form of miR-274 distributes broadly, including in synaptic boutons, muscle cells, and tracheal cells. Mature miR-274 is secreted from glia to the circulating hemolymph as an exosomal cargo, a process requiring ESCRT components in exosome biogenesis and Rab11 and Syx1A in exosome release. We further show that miR-274 can function in the neurons or tracheal cells to modulate the growth of synaptic boutons and tracheal branches, respectively. Also, miR-274 uptake into the target cells by AP-2-dependent mechanisms modulates target cell growth. In the target cells, miR-274 down-regulates Sprouty (Sty) through a targeting sequence at the sty 3' untranslated region, thereby enhancing MAPK signaling and promoting cell growth. miR-274 expressed in glia of an mir-274 null mutant is released as an exosomal cargo in the circulating hemolymph, and such glial-specific expression resets normal levels of Sty and MAPK signaling and modulates target cell growth. mir-274 mutant larvae are hypersensitive to hypoxia, which is suppressed by miR-274 expression in glia or by increasing tracheal branches. Thus, glia-derived miR-274 coordinates growth of synaptic boutons and tracheal branches to modulate larval hypoxia responses.

8.
Cancer Res Treat ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31671936

RESUMO

Purpose: To investigate the prognostic impact of EBV-miR-BHRF1-1 with chronic lymphocytic leukemia (CLL) as well as role of EBV-miR-BHRF1-1 in p53 gene. Materials and Methods: Quantitative reverse transcription-PCR (qRT-PCR) and western blotting (WB) were used to quantify EBV-miR-BHRF1-1 and p53 expression in cultured CLL. Results: p53 aberration was associated with higher expression level of Epstein-Barr virus (EBV)-microRNA (miRNA, miR)-BHRF1-1 (p<0.001) which was also an independent prognostic marker for overall survival (OS) (p=0.028; HR 5.335 [1.193, 23.846]) in 97 newly-diagnosed CLL patients after adjusted with CLL-international prognostic index (CLL-IPI). We identified EBV-miR-BHRF1-1 as a viral miRNA regulator of p53. EBV-miR-BHRF1-1 repressed luciferase reporter activity by specific interaction with the seed region within the p53 3' untranslated region. Discordance of p53 messenger RNA and protein expression was associated with high EBV-miR-BHRF1-1 levels in CLL patients and cell lines. EBV-miR-BHRF1-1 inhibition upregulated p53 protein expression, induced cell cycle arrest and apoptosis and decreased cell proliferation in cell lines. EBV-miR-BHRF1-1 mimics downregulated p53 protein expression, decreased cell cycle arrest and apoptosis, and induced cell proliferation in cell lines. Conclusion: This study supported a role of EBV-miR-BHRF1-1 in p53 regulation in vitro. Our results support the potential of EBV-miR-BHRF1-1 as a therapeutic target in EBV-associated CLL with p53 gene aberration.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31603301

RESUMO

A feasible strategy for the in situ growth of two-dimensional (2D) [Ni3(OH)2(1,4-BDC)2-(H2O)4]·2H2O (Ni-BDC; 1,4-BDC = 1,4-benzenedicarboxylate) and the subsequent partial sulfurization treatment for the decoration of nickle sulfide (NiS) is developed. The fabricated hierarchically structured Ni-BDC@NiS as a synergistic electrocatalyst shows extremely high activity toward the oxygen evolution reaction (OER). The optimal Ni-BDC@NiS catalyst acquires a current density of 20 mA cm-2 at a lower overpotential of 330 mV and low Tafel slope of 62 mV dec-1, outperforming most previously reported Ni-based sulfide catalysts. Clearly, the combination of the NiS and Ni-BDC array contributed to the improvement of electron transfer, promotion of water adsorption, and increase of rich active species. In addition, the in situ created hierarchical structure not only affords feasible access for mass transport but also strengthens structural integrity, contributing to efficient and stable OER performance. This general and effective strategy anchoring conductive active species on a porous metal-organic framework (MOF) thus provides an efficient way to fabricate synergistic electrocatalysts for the OER.

10.
Hemoglobin ; : 1-4, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645145

RESUMO

In this study, we report on a compound heterozygote for variants in the key erythroid transcription factor Krüppel-like factor 1 (KLF1) gene in a patient who presented with severe, transfusion-dependent hemolytic anemia. The red cells were normochromic and normocytic, and resembled those seen in patients with congenital nonspherocytic hemolytic anemia (CNSHA). Next generation sequencing (NGS) revealed that the patient was a compound heterozygote for the KLF1 frameshift variant c.519_525dup (p.Gly176ArgfsTer179) and a missense variant c.1012C>A (p.Pro338Thr). This report adds to the wide clinical spectrum of KLF1 gene variants. We suggest that loss of KLF1 should be considered in otherwise unexplained cases of congenital hemolytic anemia.

11.
Cell Cycle ; : 1-12, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645185

RESUMO

A keloid is defined as an overgrowth of the dense fibrous tissues that form around a wound. Since they destroy the vascular network, keloid tissues often exhibit anoxic conditions. Hypoxia-inducible factor-1α (HIF-1α) is a core factor that mediates hypoxia stress responses and regulates the hypoxic cellular and biological behaviors. In this study, we found that the expression level of HIF-1α in keloid tissue was significantly higher than that in the normal skin tissue. Hypoxia-induced HIF-1α expression significantly inhibited cellular apoptosis and promoted cellular proliferation in keloid fibroblasts but not in normal fibroblasts. Specifically, HIF-1α activated the TGF-ß/Smad and TLR4/MyD88/NF-κB pathways, and the interaction of these two pathways may promote the development of keloids. Moreover, in vivo experiments showed that the inhibition of HIF-1α significantly reduced the growth of keloids.

12.
Z Gerontol Geriatr ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31654128

RESUMO

The aim of this study was to confirm the effect of the systemic administration of melatonin on hydroxyapatite-coated titanium (HA-Ti) implants in senile osteopenic rats. For this study 24-month-old female Sprague-Dawley rats were used. The animals were randomly divided into two groups: a control group and a melatonin group and the bilateral femurs of all the rats received HA-Ti implants. Animals in the melatonin group received treatment with melatonin (30 mg/kg day). After a 12-week healing period, rats in the melatonin group revealed improved osseointegration compared to the control group, with the bone area ratio (BAR) and bone to implant contact (BIC) increased by 1.87-fold and 1.65-fold in histomorphometry, the quantitative results of implant osseointegration and peri-implant trabeculae, such as a higher bone volume per total volume (BV/TV), trabecular number (Tb.N), the mean connective density (Conn.D), trabecular thickness (Tb.Th), and a lower trabecular spacing (Tb.Sp) in micro-computed tomography (CT) evaluation and the maximum push-out force by 1.75-fold in push out tests. Additionally, compared with the control group, melatonin could significantly up-regulate the expression of the runt-related transcription factor 2 (Runx2), osteocalcin (OC) and osteoprotegerin (OPG) genes and down-regulate the expression of the RANKL gene. These findings suggest that systemic administration with melatonin is useful to improve the fixation of HA-coated implants even in osteopenic rats through promoting Runx2, OC and OPG gene expression and inhibiting RANKL gene expression.

13.
PLoS One ; 14(10): e0223169, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31609968

RESUMO

High levels of self-control are found to be associated with greater life satisfaction. To further understand this relationship, the current study examined two questions: (1) whether too much self-control reduces, rather than increases, life satisfaction, as argued by some scholars; and (2) whether engaging in prosocial behavior explains the "self-control-life satisfaction" link. To this end, we conducted survey research among adolescents (N = 1,009), university students (N = 2,620), and adult workers (N = 500). All participants answered the same self-control and life satisfaction measures, whereas prosocial behavior was assessed using different scales across samples. Results of two-line regressions failed to reveal significant inverted-U shaped association between self-control and life satisfaction across samples. Moreover, results of mediation analyses showed that across samples, high levels of self-control were related to greater life satisfaction and this association was partly mediated by prosocial behavior. In conclusion, there is no evidence showing that too much self-control impairs life satisfaction. Engaging in prosocial behavior partly explains how high self-control relates to greater well-being.

14.
Cell Signal ; : 109431, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31654721

RESUMO

The fusion oncogene, promyelocytic leukemia (PML)-retinoic acid receptor-α (RARα), is crucial for acute promyelocytic leukemia (APL) pathogenesis. Previous studies have reported that PML-RARα is cleaved by neutrophil elastase (NE), an early myeloid-specific serine protease, leading to translocation of the nuclear localization signal (NLS) of the PML protein to the N-terminal of RARα. This study was designed to evaluate the value of NLS-RARα in the early diagnosis of APL. To investigate the potential functional role of NLS-RARα in leukemogenesis, HL-60 and U937 cell lines were transfected with NLS-RARα lentivirus and negative control (LV-NC). The results showed that the induced expression of NLS-RARα down-regulated expressions of CD11b, CD11c, and CD14 compared to the LV-NC group induced by 1α, 25-dihydroxyvitamin D3(1,25(OH)2D3). This suggested that NLS-RARα overexpression inhibited granulocytic and monocytic differentiation of myeloid leukemia cells. In addition, Wright-Giemsa staining, flow cytometry, respiratory burst assay, and NBT reduction assay all confirmed the importance of NLS-RARα in differentiation. The mechanistic investigations revealed that induced NLS-RARα expression inhibited 1,25(OH)2D3-induced granulocytic differentiation by regulating the cell cycle regulators p19INK4D, p21WAF1/CIP1, cyclinD1, cyclin E1, and pRB. Furthermore, the cleaved protein NLS-RARα enhanced the oncogenicity of U937 cells in NOD/SCID mice. These findings collectively demonstrated that NLS-RARα blocked granulocytic and monocytic differentiation of myeloid leukemia cells by inhibiting the downstream targets of the RARα signal pathway and the cell cycle. This may provide a promising new target and method for diagnosing and treating APL.

15.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3745-3748, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602948

RESUMO

A new isobenzofuranone derivative was isolated from Chaenomeles sinensis by using various chromatographic techniques,including silica gel,Sephadex LH-20,MCI-gel resin and RP-HPLC. This compound was determined as 2,2-dimethyl-5-( 2-oxopropyl)-2 H-furo[3,4-h]chromen-7( 9 H)-one( 1) by NMR,MS,IR and UV spectra,and was also evaluated for its antibacterial activity. The results showed that it showed prominent antibacterial activity with MIC90 value of( 53. 7±4. 5) mg·L-1 for methicillin resistant Staphylococcus aureus( MRSA) strain. This value is close to that of levofloxacin [with MIC90 value( 50. 2± 4. 2) mg·L-1].


Assuntos
Antibacterianos/farmacologia , Benzofuranos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Rosaceae/química , Antibacterianos/isolamento & purificação , Benzofuranos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Testes de Sensibilidade Microbiana , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia
16.
Nat Commun ; 10(1): 4621, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31604910

RESUMO

Tumor subtype-specific metabolic reprogrammers could serve as targets of therapeutic intervention. Here we show that triple-negative breast cancer (TNBC) exhibits a hyper-activated cholesterol-biosynthesis program that is strongly linked to nuclear receptor RORγ, compared to estrogen receptor-positive breast cancer. Genetic and pharmacological inhibition of RORγ reduces tumor cholesterol content and synthesis rate while preserving host cholesterol homeostasis. We demonstrate that RORγ functions as an essential activator of the entire cholesterol-biosynthesis program, dominating SREBP2 via its binding to cholesterol-biosynthesis genes and its facilitation of the recruitment of SREBP2. RORγ inhibition disrupts its association with SREBP2 and reduces chromatin acetylation at cholesterol-biosynthesis gene loci. RORγ antagonists cause tumor regression in patient-derived xenografts and immune-intact models. Their combination with cholesterol-lowering statins elicits superior anti-tumor synergy selectively in TNBC. Together, our study uncovers a master regulator of the cholesterol-biosynthesis program and an attractive target for TNBC.

17.
Cardiovasc Diabetol ; 18(1): 134, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31610783

RESUMO

BACKGROUND: The aim of the present study is to examine the effects of free fatty acids (FFAs) on major cardiovascular events (MACEs) in patients with stable coronary artery disease (CAD) and different glucose metabolism status. METHODS: In this study, we consecutively enrolled 5443 patients from March 2011 to May 2015. Patients were categorized according to both status of glucose metabolism status [diabetes mellitus (DM), pre-diabetes (Pre-DM), normal glycaemia regulation (NGR)] and FFAs levels. All subjects were followed up for the occurrence of the MACEs. RESULTS: During a median of 6.7 years' follow-up, 608 MACEs occurred. A twofold higher FFAs level was independently associated with MACEs after adjusting for confounding factors [Hazard Ratio (HR): 1.242, 95% confidence interval (CI) 1.084-1.424, p value = 0.002]. Adding FFAs to the Cox model increased the C-statistic by 0.015 (0.005-0.027). No significant difference in MACEs was observed between NGR and Pre-DM groups (p > 0.05). When patients were categorized by both status of glucose metabolism and FFAs levels, medium and high FFAs were associated with significantly higher risk of MACEs in Pre-DM [1.736 (1.018-2.959) and 1.779 (1.012-3.126), all p-value < 0.05] and DM [2.017 (1.164-3.494) and 2.795 (1.619-4.824), all p-value < 0.05]. CONCLUSIONS: The present data indicated that baseline FFAs levels were associated with the prognosis in DM and Pre-DM patients with CAD, suggesting that FFAs may be a valuable predictor in patients with impaired glucose metabolism.

18.
Oxid Med Cell Longev ; 2019: 8768164, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31612078

RESUMO

Chronic hypertension, valvular heart disease, and heart infarction cause cardiac remodeling and potentially lead to a series of pathological and structural changes in the left ventricular myocardium and a progressive decrease in heart function. Angiotensin II (AngII) plays a key role in the onset and development of cardiac remodeling. Many microRNAs (miRNAs), including miR-154-5p, may be involved in the development of cardiac remolding, but the underlying molecular mechanisms remain unclear. We aimed to characterize the function of miR-154-5p and reveal its mechanisms in cardiac remodeling induced by AngII. First, angiotensin II led to concurrent increases in miR-154-5p expression and cardiac remodeling in adult C57BL/6J mice. Second, overexpression of miR-154-5p to a level similar to that induced by AngII was sufficient to trigger cardiomyocyte hypertrophy and apoptosis, which is associated with profound activation of oxidative stress and inflammation. Treatment with a miR-154-5p inhibitor noticeably reversed these changes. Third, miR-154-5p directly inhibited arylsulfatase B (Arsb) expression by interacting with its 3'-UTR and promoted cardiomyocyte hypertrophy and apoptosis. Lastly, the angiotensin type 1 receptor blocker telmisartan attenuated AngII-induced cardiac hypertrophy, apoptosis, and fibrosis by blocking the increase in miR-154-5p expression. Moreover, upon miR-154-5p overexpression in isolated cardiomyocytes, the protective effect of telmisartan was partially abolished. Based on these results, increased cardiac miR-154-5p expression is both necessary and sufficient for AngII-induced cardiomyocyte hypertrophy and apoptosis, suggesting that the upregulation of miR-154-5p may be a crucial pathological factor and a potential therapeutic target for cardiac remodeling.

19.
J Agric Food Chem ; 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31638789

RESUMO

Most common sphingolipids are comprised of "typical" sphingoid bases (sphinganine, sphingosine and structurally related compounds) and are produced via the condensation of L-serine with a fatty acyl-CoA by serine palmitoyltransferase. Some organisms, including mammals, also produce "atypical" sphingoid bases that lack a 1-hydroxyl-group due to the utilization of L-alanine or glycine instead of L-serine, resulting in the formation of 1-deoxy- or 1-desoxymethyl-sphingoid bases, respectively. Elevated production of "atypical" sphingolipids has been associated with human disease, but 1-deoxy-sphingoid bases have also been found to have potential as anti-cancer compounds; hence the importance of knowing more about the occurrence of these compounds in food. Most of the "typical" and "atypical" sphingoid bases are found as the N-acyl metabolites (e.g., ceramides and 1-deoxyceramides) in mammals, but this has not been uniformly assessed in previous studies, nor determined for other biological sources--including those that are consumed as food. Therefore, we developed a method for the quantitative analysis of "typical" and "atypical" sphingoid bases and their N-acyl-derivatives by reverse-phase liquid chromatography coupled to electrospray-ionization tandem-mass spectrometry. Based on these analyses, there was considerable variability in the amounts and molecular subspecies of atypical sphingoid bases and their N-acyl metabolites found in different edible sources. These findings demonstrate that a broader assessment of the types of sphingolipids in foods is needed because some diets might contain sufficient amounts of atypical as well as typical sphingolipids that could have beneficial, or possibly have deleterious effects on human health.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31640856

RESUMO

Before fertilization, ovulated mammalian oocytes are arrested at the metaphase of second meiosis (MII), which is maintained by the so-called cytostatic factor (CSF). It is well known that the continuous synthesis and accumulation of cyclin B is critical for maintaining the CSF-mediated MII arrest. Recent studies by us and others have shown that Ccnb3 is required for the metaphase-to-anaphase transition during the first meiosis of mouse oocytes, but whether Ccnb3 plays a role in MII arrest and exit remains unknown. Here, we showed that the protein level of Ccnb3 gradually decreased during oocyte meiotic maturation, and exogenous expression of Ccnb3 led to release of MII arrest, degradation of securin, separation of sister chromatids, extrusion of the second polar body (PB2), and finally entry into interphase. These phenotypes could be rescued by inhibition of Wee1B or CDK2. Our results indicate that Ccnb3 plays a critical regulatory role in MII arrest and exit in mouse oocytes.

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