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1.
Sci Adv ; 6(20): eaaz0480, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32426496

RESUMO

Although multiple signaling pathways work synergistically in various niches to control stem cell self-renewal and differentiation, it remains poorly understood how they cooperate with one another molecularly. In the Drosophila ovary, Hh and Wnt pathways function in the niche to promote germline stem cell (GSC) progeny differentiation. Here, we show that glypican Dlp-mediated Hh and Wnt signaling interdependence operates in the niche to promote GSC progeny differentiation by preventing BMP signaling. Hh/Wnt-mediated dlp repression is essential for their signaling interdependence in niche cells and for GSC progeny differentiation by preventing BMP signaling. Mechanistically, Hh and Wnt downstream transcription factors directly bind to the same dlp regulatory region and recruit corepressors composed of transcription factor Croc and Egg/H3K9 trimethylase to repress Dlp expression. Therefore, our study reveals a novel mechanism for Hh/Wnt signaling-mediated direct dlp repression and a novel regulatory mechanism for Dlp-mediated Hh/Wnt signaling interdependence in the GSC differentiation niche.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32277024

RESUMO

It has long been predicted that oscillatory behavior exists in reactivity as a function of collision energy for heavy-light-heavy (HLH) chemical reactions in which a light atom is transferred between two heavy atoms or groups of atoms, but direct observation of such a behavior in bimolecular reactions remains a challenge. Here we report a joint theoretical and crossed-molecular-beam study on the Cl + CH4 → HCl + CH3 reaction. A distinctive peak at a collision energy of 0.15 eV for the CH3(v = 0) product was experimentally detected in the backward scattering direction. Detailed quantum-dynamics calculations on a highly accurate potential energy surface revealed that this feature originates from the reactivity oscillation in this HLH polyatomic reaction. We anticipate that such reactivity oscillations exist in many HLH reactions involving polyatomic reagents.

3.
Signal Transduct Target Ther ; 5(1): 21, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32296014

RESUMO

Internal tandem duplication (ITD) mutations of FMS-like tyrosine kinase-3 (FLT3) are the most frequent genetic alterations in acute myeloid leukemia (AML) and predict a poor prognosis. FLT3 tyrosine kinase inhibitors (TKIs) provide short-term clinical responses, but the long-term prognosis of FLT3/ITD+ AML patients remains poor. Notch signaling is important in numerous types of tumors. However, the role of Notch signaling in FLT3/ITD+ AML remains to be elucidated. In the current study, we found that Notch signaling was activated upon FLT3-TKI treatment in FLT3/ITD+ cell lines and primary cells. As Notch signaling can be blocked by γ-secretase inhibitors (GSIs), we examined the combinatorial antitumor efficacy of FLT3-TKIs and GSIs against FLT3/ITD+ AML and explored the underlying molecular mechanisms. As a result, we observed synergistic cytotoxic effects, and the treatment preferentially reduced cell proliferation and induced apoptosis in FLT3/ITD+ AML cell lines and in primary AML cells. Furthermore, the combination of FLT3-TKI and GSI eradicated leukemic cells and prolonged survival in an FLT3/ITD+ patient-derived xenograft AML model. Mechanistically, differential expression analysis suggested that CXCR3 may be partially responsible for the observed synergy, possibly through ERK signaling. Our findings suggest that combined therapies of FLT3-TKIs with GSI may be exploited as a potential therapeutic strategy to treat FLT3/ITD+ AML.

4.
Addict Biol ; : e12888, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32115811

RESUMO

The gray matter volume (GMV) of the putamen has been reported to be regulated by kinectin 1 gene (KTN1). As a hub of the dopaminergic circuit, the putamen is widely implicated in the etiological processes of substance use disorders (SUD). Here, we aimed to identify robust and reliable associations between KTN1 SNPs and SUD across multiple samples. We examined the associations between SUD and KTN1 SNPs in four independent population-based or family-based samples (n = 10,209). The potential regulatory effects of the risk alleles on the putamen GMVs, the effects of alcohol, nicotine, marijuana and cocaine on KTN1 mRNA expression, and the relationship between KTN1 mRNA expression and SUD were explored. We found that a total of 23 SNPs were associated with SUD across at least two independent samples (1.4 × 10-4 ≤ p ≤ 0.049), including one SNP (rs12895072) across three samples (8.8 × 10-3 ≤ p ≤ 0.049). Four other SNPs were significantly or suggestively associated with SUD only in European-Australians (4.8 × 10-4 ≤ p ≤ 0.058). All of the SUD-risk alleles of these 27 SNPs increased (ß > 0) the putamen GMVs and represented major alleles (f > 0.5) in Europeans. Twenty-two SNPs were potentially biologically functional. Alcohol, nicotine and cocaine significantly affected the KTN1 mRNA expression, and the KTN1 mRNA was differentially expressed between nicotine or cocaine dependent and control subjects. We concluded that there was a replicable and robust relationship among the KTN1 variants, KTN1 mRNA expression, putamen GMVs, molecular effects of substances, and SUD, suggesting that some risk KTN1 alleles might increase kinectin 1 expression in the putamen, altering putamen structures and functions, and leading to SUD.

5.
BMC Cancer ; 20(1): 195, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32143579

RESUMO

BACKGROUND: Donor acute lymphoblastic leukemia with recipient intact is a rare condition. We report a case of donor developing acute lymphoblastic leukemia 8 yrs after donating both bone marrow and peripheral blood hematopoietic stem cells. CASE PRESENTATION: This case report describes a 51-year old female diagnosed with acute lymphoblastic leukemia who donated both bone marrow and peripheral blood stem cells 8 yrs ago for her brother with severe aplastic anemia. Whole exome sequencing revealed leukemic genetic lesions (SF3B1 and BRAF mutation) only appeared in the donor sister, not the recipient, and an unusual type of hematopoietic stem cell transplantation with the recipient's peripheral blood stem cells was done. The patient remained in remission for 3 months before disease relapsed. CD19 CAR-T therapy followed by HLA-identical unrelated hematopoietic stem cell transplantation was applied and the patient remains in remission for 7 months till now. CONCLUSIONS: This donor leukemia report supports the hypothesis that genetic lesions happen randomly in leukemogenesis. SF3B1 combined with BRAF mutation might contribute to the development of acute lymphoblastic leukemia.

6.
J Am Chem Soc ; 142(12): 5526-5530, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32131597

RESUMO

Planar, terpyridine-based metal complexes with the Sierpinski triangular motif and alkylated corners undergo a second self-assembly event to give megastructural Sierpinski pyramids; assembly is driven by the facile lipophilic-lipophilic association of the alkyl moieties and complementary perfect fit of the triangular building blocks. Confirmation of the 3D, pyramidal structures was verified and supported by a combination of TEM, AFM, and multiscale simulation techniques.

7.
J Mol Biol ; 432(7): 2141-2163, 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32087196

RESUMO

Cells have evolved molecular chaperones that modulate phase separation and misfolding of amyloidogenic proteins to prevent neurodegenerative diseases. Protein disulfide isomerase (PDI), mainly located at the endoplasmic reticulum and also present in the cytosol, acts as both an enzyme and a molecular chaperone. PDI is observed to be S-nitrosylated in the brain of Alzheimer's disease patients, but the mechanism has remained elusive. We herein report that both wild-type PDI and its quadruple cysteine mutant only having chaperone activity, significantly inhibit pathological phosphorylation and abnormal aggregation of Tau in cells, and significantly decrease the mitochondrial damage and Tau cytotoxicity resulting from Tau aberrant aggregation, highlighting the chaperone property of PDI. More importantly, we show that wild-type PDI is selectively recruited by liquid droplets of Tau, which significantly inhibits phase separation and stress granule formation of Tau, whereas S-nitrosylation of PDI abrogates the recruitment and inhibition. These findings demonstrate how phase separation of Tau is physiologically regulated by PDI and how S-nitrosylation of PDI, a perturbation in this regulation, leads to disease.

8.
BMC Genomics ; 21(1): 139, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041524

RESUMO

BACKGROUND: Lead (Pb) pollution in soil has become one of the major environmental threats to plant growth and human health. Safe utilization of Pb contaminated soil by phytoremediation require Pb-tolerant rapeseed (Brassica napus L.) accessions. However, breeding of new B. napus cultivars tolerance to Pb stress has been restricted by limited knowledge on molecular mechanisms involved in Pb tolerance. This work was carried out to identify genetic loci related to Pb tolerance during seedling establishment in rapeseed. RESULTS: Pb tolerance, which was assessed by quantifying radicle length (RL) under 0 or 100 mg/L Pb stress condition, shown an extensive variation in 472 worldwide-collected rapeseed accessions. Based on the criterion of relative RL > 80%, six Pb-tolerant genotypes were selected. Four quantitative trait loci (QTLs) associated with Pb tolerance were identified by Genome-wide association study. The expression level of nine promising candidate genes, including GSTUs, BCATs, UBP13, TBR and HIPP01, located in these four QTL regions, were significantly higher or induced by Pb in Pb-tolerant accessions in comparison to Pb-sensitive accessions. CONCLUSION: To our knowledge, this is the first study on Pb-tolerant germplasms and genomic loci in B. napus. The findings can provide valuable genetic resources for the breeding of Pb-tolerant B. napus cultivars and understanding of Pb tolerance mechanism in Brassica species.

9.
Proc Natl Acad Sci U S A ; 117(7): 3603-3609, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32015133

RESUMO

5-Methylcytosine (m5C) is a RNA modification that exists in tRNAs and rRNAs and was recently found in mRNAs. Although it has been suggested to regulate diverse biological functions, whether m5C RNA modification influences adult stem cell development remains undetermined. In this study, we show that Ypsilon schachtel (YPS), a homolog of human Y box binding protein 1 (YBX1), promotes germ line stem cell (GSC) maintenance, proliferation, and differentiation in the Drosophila ovary by preferentially binding to m5C-containing RNAs. YPS is genetically demonstrated to function intrinsically for GSC maintenance, proliferation, and progeny differentiation in the Drosophila ovary, and human YBX1 can functionally replace YPS to support normal GSC development. Highly conserved cold-shock domains (CSDs) of YPS and YBX1 preferentially bind to m5C RNA in vitro. Moreover, YPS also preferentially binds to m5C-containing RNAs, including mRNAs, in germ cells. The crystal structure of the YBX1 CSD-RNA complex reveals that both hydrophobic stacking and hydrogen bonds are critical for m5C binding. Overexpression of RNA-binding-defective YPS and YBX1 proteins disrupts GSC development. Taken together, our findings show that m5C RNA modification plays an important role in adult stem cell development.

10.
J Gastroenterol Hepatol ; 35(2): 343-352, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31318997

RESUMO

BACKGROUND AND AIM: Diabetes mellitus (DM) is a common complication of idiopathic chronic pancreatitis (ICP), which impairs the quality of life for patients. This study aimed to identify risk factors and develop nomogram for DM in ICP to help early diagnosis. METHODS: Idiopathic chronic pancreatitis patients admitted to our center from January 2000 to December 2013 were included. Cumulative rates of DM were calculated by Kaplan-Meier method. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on training cohort, risk factors for DM were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively. RESULTS: Totally, 1633 patients with ICP were finally enrolled. The median follow-up duration was 9.8 years. DM was found in 26.3% (430/1633) of patients after the onset of CP. Adult at onset of ICP, biliary stricture at/before diagnosis of CP, steatorrhea at/before diagnosis of CP, and complex pathologic changes in main pancreatic duct were identified risk factors for DM development. The nomogram achieved good concordance indexes in the training and validation cohorts, respectively, with well-fitted calibration curves. CONCLUSIONS: Risk factors were identified, and nomogram was developed to determine the risk of DM in ICP patients. Patients with one or more of the risk factors including adult at onset of ICP, biliary stricture at/before diagnosis of CP, steatorrhea at/before diagnosis of CP, and complex pathologic changes in main pancreatic duct have higher incidence of DM.

11.
Bioorg Chem ; 95: 103525, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31887474

RESUMO

The phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) have been regarded as promising targets for the treatment of cancer. Herein, we synthesized a new series of substituted 2-(thiophen-2-yl)-1,3,5-triazine derivatives as novel PI3Kα/mTOR dual inhibitors for cancer therapy. All compounds were evaluated for the IC50 values against three cancer cell lines (A549, MCF-7 and Hela). Most of the target compounds exhibited moderate to excellent anti-tumor activities against these three tested cancer cell lines especially against A549 and Hela cancer cell lines. Among them, the most promising compound 13g showed excellent anti-tumor potency for A549, MCF-7 and Hela cell lines with IC50 values of 0.20 ± 0.05 µM, 1.25 ± 0.11 µM and 1.03 ± 0.24 µM, respectively. Notably, according to the result of enzymatic activity assay, compound 13g was identified as a novel PI3Kα/mTOR dual inhibitor, which had an approximately 10-fold improvement in mTOR inhibition, compared to the class I PI3K inhibitor 1 (pictilisib, GDC-0941), with IC50 values of 525 nM to 48 nM. And western blot analysis indicated compound 13g could efficiently suppress the phosphorylation of AKT at the dose of 0.1 µM, which further demonstrated compound 13g had significant inhibitory effect on the PI3K/Akt/mTOR pathway. Furthermore, compound 13g could stimulate A549 cells arrest at G0/G1 phase in a dose-dependent manner, and induced apoptosis at a low concentration.

12.
IEEE Trans Image Process ; 29: 44-56, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31329555

RESUMO

Hyperspectral images (HSIs) are often degraded by a mixture of various types of noise during the imaging process, including Gaussian noise, impulse noise, and stripes. Such complex noise could plague the subsequent HSIs processing. Generally, most HSI denoising methods formulate sparsity optimization problems with convex norm constraints, which over-penalize large entries of vectors, and may result in a biased solution. In this paper, a nonconvex regularized low-rank and sparse matrix decomposition (NonRLRS) method is proposed for HSI denoising, which can simultaneously remove the Gaussian noise, impulse noise, dead lines, and stripes. The NonRLRS aims to decompose the degraded HSI, expressed in a matrix form, into low-rank and sparse components with a robust formulation. To enhance the sparsity in both the intrinsic low-rank structure and the sparse corruptions, a novel nonconvex regularizer named as normalized ε -penalty, is presented, which can adaptively shrink each entry. In addition, an effective algorithm based on the majorization minimization (MM) is developed to solve the resulting nonconvex optimization problem. Specifically, the MM algorithm first substitutes the nonconvex objective function with the surrogate upper-bound in each iteration, and then minimizes the constructed surrogate function, which enables the nonconvex problem to be solved in the framework of reweighted technique. Experimental results on both simulated and real data demonstrate the effectiveness of the proposed method.


Assuntos
Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Razão Sinal-Ruído
13.
Dalton Trans ; 48(48): 17800-17809, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31769766

RESUMO

Hg2+ is highly toxic and hazardous and widely found in polluted water. To remove mercury ions from wastewater, there is an urgent need to investigate and develop new adsorbents. Herein, we synthesized three novel thioether-based metal-organic frameworks (MOFs) through a facile diffusion method or a solvothermal strategy, i.e. [(ZnCl2)3(L1)2·χ(solvent)]n (1), [(Cu2I3O2)4(CH4N0.5)4(L1)4(DMA)4·3(H2O)·χ(solvent)]n (2) and [(CuBr2)2(L2)2 CH3CN·χ(solvent)]n (3), where L1 = 1,3,5-tris((pyridin-4-ylthio)methyl)benzene and L2 = 2,4,6-trimethoxy-1,3,5-tris((pyridin-4-ylthio)methyl)benzene. The obtained thioether-based MOFs were characterized by single-crystal X-ray diffraction, Fourier transform infrared spectroscopy, elemental analysis and thermogravimetric analysis. Further studies revealed that they could remove Hg2+ from water. They have high adsorptivity (up to 362 mg g-1) and are highly efficient in removing Hg2+ (up to 95%). Besides, these MOFs can be recycled and can selectively remove Hg2+ from water in the presence of other metal ions. Consequently, these MOFs are highly promising candidates for the selective absorption and removal of mercury ions from water.

14.
Medicine (Baltimore) ; 98(48): e17984, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770208

RESUMO

Pediatric patients suffer from chronic pancreatitis (CP), especially those with diabetes mellitus (DM). This study aimed to identify the incidence of and risk factors for DM in pediatric CP.CP patients admitted to our center from January 2000 to December 2013 were assigned to the pediatric (<18 years old) and adult group according to their age at onset of CP. Cumulative rates of DM and risk factors for both groups were calculated and identified.The median follow-up duration for the whole cohort was 7.6 years. In these 2153 patients, 13.5% of them were pediatrics. The mean age at the onset and the diagnosis of CP in pediatrics were 11.622 and 19.727, respectively. DM was detected in 13.1% patients and 31.0% patients in the pediatric group and adult group, respectively. Age at the onset of CP, smoking history, body mass index (BMI), and etiology of CP were identified risk factors for DM in pediatrics.DM was detected in 13.1% pediatric patients. Age at the onset of CP, smoking history, BMI, and etiology of CP were identified risk factors for the development of DM in pediatric CP patients. The high-risk populations were suggested to be monitored frequently. They could also benefit from a lifestyle modification.


Assuntos
Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Pancreatite Crônica/complicações , Adolescente , Criança , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
15.
Chin J Integr Med ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31768871

RESUMO

OBJECTIVE: To investigate the phenolic composition, antioxidant properties, and hepatoprotective mechanisms of polyphenols from green tea extract (GTP) in carbon tetrachloride (CCl4)-induced acute liver injury mouse model. METHODS: High-performance liquid chromatography was used to analyze the chemical composition of the extract. Antioxidant activity of GTP was assessed by O2∙-, OH∙, DPPH∙, and ferric-reducing antioxidant power (FRAP) assay in vitro. Sixty Kunming mice were divided into 6 groups including control, model, low-, medium-, and high-doses GTP (200, 400, 800 mg/kg) and vitamin E (250 mg/kg) groups, 10 in each group. GTP and vitamin E were administered at a level of abovementioned doses twice per day for 7 days prior to exposure to a single injection of CCl4. Hepatoprotective effects of GTP were evaluated in a CCl4-induced mouse model of acute liver injury, using commercial enzyme linked immunosorbent assay kits, histopathological observation, terminal deoxynucleotidyl transferase-mediated dUTPNick-end labeling (TUNEL) assay and Western blot. RESULTS: GTP contained 98.56 µg gallic acid equivalents per milligram extract total polyphenols, including epicatechingallate, epigallocatechin gallate, epicatechin, and epigallocatechin. Compared with the model group, low-, medium-, or high doses GTP significantly decreased serum levels of alanine aminotransferase and aspartate transaminase (P<0.01). Histopathological observation confirmed that pretreatment of GTP prevented swelling and necrosis in CCl4-exposed hepatocytes. Hepatoprotective effects of low-, medium-, and high-dose GTP were associated with eliminating free radicals and improving superoxide dismutase, catalase, and glutathione peroxidase activity in the liver. Additionally, low-, medium-, and high-dose GTP decreased cell apoptosis in the CCl4-exposed liver (P<0.01). Phosphorylated nuclear factor kappa-B (NF-κB), p53, Bcl-2 associated x protein/B-cell lymphoma/leukemia-2 gene, cytochrome C, and cleaved caspase-3 levels were downregulated compared with the model group (P<0.01). CONCLUSION: GTP achieves hepatoprotective effects by improving hepatic antioxidant status and preventing cell apoptosis through caspase-3-dependent signaling pathways.

16.
PeerJ ; 7: e7690, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576242

RESUMO

Background: Lecanicillium lecanii is an entomopathogenic fungi, which was isolated from insects suffering from disease. Now, it is an effective bio-control resource that can control agricultural pests such as whitefly and aphids. There are many studies on the control of various agricultural pests by L. lecanii, but no report on its control of Bemisia tabaci biotype-Q exists. In this work, we studied the susceptibility of B. tabaci Q-biotype (from Ningxia, China) to L. lecanii JMC-01 in terms of nymph mortality and the changes in detoxifying protective enzymes activities. Methods: B. tabaci nymphs were exposed to L. lecanii JMC-01 conidia by immersion with the host culture. Mortality was assessed daily for all nymph stages. The detoxifying and protective enzyme activity changes, weight changes, and fat, and water contents of the nymphs were determined spectrophotometrically. Results: All instars of B. tabaci died after being infested with 1 × 108 conidia/mL. The 2nd-instar nymphs were the most susceptible, followed by the 3rd-instar nymphs. The corrected cumulative mortality of the 2nd- and 3rd-instar nymphs was 82.22% and 75.55%, respectively. The levels of detoxifying and protective enzymes initially increased and then decreased. The highest activities of carboxylesterase, acetylcholinesterase, peroxidase, and catalase occurred on the 3rd day, reaching 10.5, 0.32, 20, and 6.3 U/mg prot, respectively. These levels were 2.2-, 4.3-, 2.4-, and 1.4-fold the control levels, respectively. The highest activities of glutathione-S transferase and superoxide dismutase on the 2nd day were, respectively, 64 and 43.5 U/mg prot. These levels were, respectively, 2.7 and 1.1-fold that of the control level. The water and fat content in the infected B. tabaci nymphs decreased and differed significantly from the control levels. The weight increased continuously in the first 24 h, decreasing thereafter. At 72 h, the infestation level was about 0.78-fold that of the control level. Conclusions: The studied L. lecanii JMC-01 strain is pathogenic to the B. tabaci Q-biotype. This strain interferes with the normal functioning of detoxifying and protective enzymes, and is also involved in the disruption of normal physiological metabolism in B. tabaci.

17.
Life Sci Alliance ; 2(5)2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31619466

RESUMO

Piwi-interacting RNAs (piRNAs) are important for repressing transposable elements (TEs) and modulating gene expression in germ cells, thereby maintaining genome stability and germ cell function. Although they are also important for maintaining germline stem cells (GSCs) in the Drosophila ovary by repressing TEs and preventing DNA damage, piRNA expression has not been investigated in GSCs or their early progeny. Here, we show that the canonical piRNA clusters are more active in GSCs and their early progeny than late germ cells and also identify more than 3,000 new piRNA clusters from deep sequencing data. The increase in piRNAs in GSCs and early progeny can be attributed to both canonical and newly identified piRNA clusters. As expected, piRNA clusters in GSCs, but not those in somatic support cells (SCs), exhibit ping-pong signatures. Surprisingly, GSCs and early progeny express more TE transcripts than late germ cells, suggesting that the increase in piRNA levels may be related to the higher levels of TE transcripts in GSCs and early progeny. GSCs also have higher piRNA levels and lower TE levels than SCs. Furthermore, the 3' UTRs of 171 mRNA transcripts may produce sense, antisense, or dual-stranded piRNAs. Finally, we show that alternative promoter usage and splicing are frequently used to modulate gene function in GSCs and SCs. Overall, this study has provided important insight into piRNA production and TE repression in GSCs and SCs. The rich information provided by this study will be a beneficial resource to the fields of piRNA biology and germ cell development.

18.
Clin Sci (Lond) ; 133(19): 2029-2044, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31654570

RESUMO

Fibroblast growth factor 21 (FGF21) is known as a potent metabolic regulator but its protective mechanisms against lipotoxicity-induced ß-cell dysfunction and apoptosis remain elusive. Here, we aimed to examine the regulatory pathways whereby FGF21 mediates islet lipid metabolism in lipotoxicity-treated cells and animal models. Rat ß-cell line (INS-1E cells) and islets isolated from C57/BL6J mice were exposed to palmitic acid (PA) with/without FGF21, mimicking lipotoxic conditions. Resultant insulin secretion and intracellular signaling were analyzed with Western blotting and RNA-seq. C57/BL6J and global FGF21 knockout (KO) mice were fed with a high-fat diet (HFD) to induce lipotoxicity and given with a long-acting mimetic of FGF21. Insulin resistance and ß-cell function were then assessed using homeostasis model assessment of insulin resistance (HOMA-IR) and insulinogenic index. FGF21 ameliorated PA-induced lipid accumulation, reversed cell apoptosis, and enhanced glucose-stimulated insulin secretion (GSIS) as impaired by lipotoxicity in islet ß-cells. Mechanistically, FGF21 exerted its beneficial effects through activation of AMPK-ACC (acetyl-CoA carboxylase) pathway and peroxisome proliferation-activated receptors (PPARs) δ/γ signaling, thus increasing the levels of carnitine palmitoyltransferase-1A (CPT1A) and leading to increased fatty acid (FA) oxidation and reduced lipid deposition in ß-cells. Interestingly, FGF21 reduced PA-induced cell death via restoration of the expression of apoptosis inhibitor Birc3. In vivo studies further showed that FGF21 is critical for islet insulinogenic capacity and normal function in the context of HFD-treated animals. FGF21 down-regulates islet cell lipid accumulation, probably via activation of AMPK-ACC and PPARδ/γ signaling, and reduces cell death under lipotoxicity, indicating that FGF21 is protective against lipotoxicity-induced ß-cell dysfunction and apoptosis.

19.
Chin J Traumatol ; 22(5): 296-299, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31481277

RESUMO

The incidence of chronic wounds has been increasing over the past 20 years. However, the standardized diagnosis and treatment practice of chronic refractory wounds have not been established. In addition, the properties of the wound are characterized by morphology and thus correct description of the wound in medical history collection plays a vital role, which directly affects the definitive diagnosis. To develop more accurate format of clinical history record which can correctly reflect a patient's course and treatment progress, and to standardize the medical history record of chronic refractory wounds, at the national or regional level, we designed the WoundCareLog APP. It acts as a recording and communication tool for wound healing specialists at all levels of medical institutions in China. The WoundCareLog APP is fully compatible to meet the criteria and requirements of conventional medical records by embedding 9 modules. In addition, the demands for morphological description of wounds in wound healing diagnosis and treatment have been fulfilled by enroll of digital imaging technology to overcome the inadequacies of traditional medical history records.


Assuntos
Aplicativos Móveis , Cicatrização , Ferimentos e Lesões/diagnóstico , China , Doença Crônica , Humanos , Ferimentos e Lesões/patologia , Ferimentos e Lesões/fisiopatologia , Ferimentos e Lesões/terapia
20.
Nat Plants ; 5(8): 822-832, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31383969

RESUMO

The non-random three-dimensional (3D) organization of the genome in the nucleus is critical to gene regulation and genome function. Using high-throughput chromatin conformation capture, we generated chromatin interaction maps for Brassica rapa and Brassica oleracea at a high resolution and characterized the conservation and divergence of chromatin organization in these two species. Large-scale chromatin structures, including A/B compartments and topologically associating domains, are notably conserved between B. rapa and B. oleracea, yet their KNOT structures are highly divergent. We found that genes retained in less fractionated subgenomes exhibited stronger interaction strengths, and diploidization-resistant duplicates retained in pairs or triplets are more likely to be colocalized in both B. rapa and B. oleracea. These observations suggest that spatial constraint in duplicated genes is correlated to their biased retention in the diploidization process. In addition, we found strong similarities in the epigenetic modification and Gene Ontology terms of colocalized paralogues, which were largely conserved across B. rapa and B. oleracea, indicating functional constraints on their 3D positioning in the nucleus. This study presents an investigation of the spatial organization of genomes in Brassica and provides insights on the role of 3D organization in the genome evolution of this genus.

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