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1.
J Hum Genet ; 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32427951

RESUMO

Human Y-chromosome haplogroup C2b-F1067 is one of the dominant paternal lineages of populations in Eastern Eurasia. In order to explore the origin, diversification, and expansion of this haplogroup, we generated 206 new Y-chromosome sequences from C2b-F1067 males and coanalyzed 220 Y-chromosome sequences of this haplogroup. BEAST software was used to reconstruct a revised phylogenetic tree of haplogroup C2b-F1067 with age estimates. The revised phylogeny of C2b-F1067 included 155 sublineages, 1986 non-private variants, and >6000 private variants. The age estimation suggested that the initial splitting of C2b-F1067 happened at about 32.8 thousand years ago (kya) and the major sublineages of this haplgroup experienced continuous expansion in the most recent 10,000 years. We identified numerous sublineages that were nearly specific for Korean, Mongolian, Chinese, and other ethnic minorities in China. In particular, we evaluated the candidate-specific lineage for the Dayan Khan family and the Confucius family, the descendants of the ruling family of the Chinese Shang dynasty. These findings suggest that ancient populations with varied C2b-F1067 sublineages played an important role during the formation of most modern populations in Eastern Eurasia, and thus eventually became the founding paternal lineages of these populations.

2.
Biochem Biophys Res Commun ; 526(4): 906-912, 2020 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-32279997

RESUMO

C-phycocyanin (C-PC) is a kind of photosynthetically assisted pigment, which is ubiquitous in cyanobacteria cells. We investigated the effect of C-PC on non-alcoholic fatty liver disease (NAFLD) and its mechanism. Through oil red O staining, TC/TG detection, liver SOD/MDA detection and liver H&E staining, we found that C-PC could significantly reduce the lipid accumulation in the steatosis L02 cells and the liver of non-alcoholic steatohepatitis (NASH) mice, and improve the antioxidant capacity of liver. The results of Western Blotting showed that C-PC upregulated the expression of AMPK phosphorylation and downregulated SREBP-1c and its target genes ACC and FAS expression levels. Furthermore, C-PC also upregulated the expression of transcription factor PPARα, which was regulated by AMPK, and its target genes CPT1 level. In addition, C-PC could promote AMPK phosphorylation in hepatocytes while increasing the phosphorylation level of ACC in vivo and in vitro. Besides, C-PC could also improve the liver inflammatory infiltration by upregulated the expression of PPARγ and downregulated the expression of CD36, IL6 and TNFα. These results indicate that C-PC may improve hepatic lipid accumulation and inflammation in the non-alcoholic fatty liver mice by activating AMPK pathway of hepatocytes. The finding provides important help for the research and development of C-PC in the nutraceuticals and therapeutics of NAFLD.

3.
Oxid Med Cell Longev ; 2020: 6431459, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32184918

RESUMO

Oxidative stress has been recognized as the contributor to diabetic peripheral neuropathy (DPN). Antioxidant strategies have been most widely explored; nevertheless, whether antioxidants alone prevent DPN still remains inconclusive. In the present study, we established an in vitro DPN cell model for drug screening using Schwann RSC96 cells under high glucose (HG) stimulation, and we found that salvianolic acid A (SalA) mitigated HG-induced injury evidenced by cell viability and myelination. Mechanistically, SalA exhibited strong antioxidative effects by inhibiting 1,1-diphenyl-2-picrylhydrazyl (DPPH) and reducing reactive oxygen species (ROS), malondialdehyde (MDA), and oxidized glutathione (GSSG) content, as well as upregulating antioxidative enzyme mRNA expression. In addition, SalA significantly extenuated neuroinflammation with downregulated inflammatory factor mRNA expression. Furthermore, SalA improved the mitochondrial function of HG-injured Schwann cells by scavenging mitochondrial ROS, decreasing mitochondrial membrane potential (MMP), and enhancing ATP production, as well as upregulating oxidative phosphorylation gene expression. More importantly, we identified nuclear factor-E2-related factor 2 (Nrf2) as the upstream regulator which mediated protective effects of SalA on DPN. SalA directly bound to the Kelch domain of Kelch-like ECH-associated protein 1 (Keap1) and thus disrupted the interaction of Nrf2 and Keap1 predicted by LibDock of Discovery Studio. Additionally, SalA significantly inhibited Nrf2 promoter activity and downregulated Nrf2 mRNA expression but without affecting Nrf2 protein expression. Interestingly, SalA upregulated the nuclear Nrf2 expression and promoted Nrf2 nuclear translocation by high content screening assay, which was confirmed to be involved in its antiglucotoxicity effect by the knockdown of Nrf2 in RSC96 cells. In KK-Ay mice, we demonstrated that SalA could effectively improve the abnormal glucose and lipid metabolism and significantly protect against DPN by increasing the mechanical withdrawal threshold and sciatic nerve conduction velocity and restoring the ultrastructural impairment of the injured sciatic nerve induced by diabetes. Hence, SalA protected against DPN by antioxidative stress, attenuating neuroinflammation, and improving mitochondrial function via Nrf2. SalA may be prospective therapeutics for treating DPN.

4.
Mol Phylogenet Evol ; 146: 106758, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32028031

RESUMO

The Bambusa-Dendrocalamus-Gigantochloa complex (BDG complex) is the most diversified and phylogenetically recalcitrant group of the paleotropical woody bamboos. Species of this complex occur in tropical and subtropical Asia and most of them are of great economic, cultural and ecological value. The lack of resolution achieved through the analyses of previous molecular datasets has long confounded its phylogenetic estimation and generic delimitation. Here, we adopted a ddRAD-seq strategy to investigate phylogenetic relationships of the four main genera (Bambusa, Dendrocalamus, Gigantochloa, and Melocalamus) in the BDG complex. A total of 102 species were sampled, and SNP data were generated. Both MP and ML analyses of the ddRAD-seq data resulted in a well-resolved topology with Gigantochloa and Melocalamus confirmed as monophyletic, and Melocalamus resolved as sister to the rest of the complex. Bambusa and Dendrocalamus were both resolved as paraphyletic. The phylogenetic relationships were mostly supported by morphological evidence including characters of the branch complement, rachilla, lodicules, filaments and stigma. We also generated and assembled complete plastid genomes of 48 representative species. There were conflicts between the plastome and the ddRAD topologies. Our study demonstrated that RAD-seq can be used to reconstruct evolutionary history of lineages such as the bamboos where ancient hybridization and polyploidy play a significant role. The four genera of the BDG complex have a complex evolutionary history which is likely a product of ancient introgression events.

5.
Life Sci ; 245: 117352, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32006527

RESUMO

AIMS: The depot-specific differences in lipidome of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) reflect heterogeneity of white adipose tissue (WAT), which plays a central role in its distinct response to outside stimuli. However, the detailed lipidome of depot-specific WAT is largely unknown, especially the minor constitutes including phospholipid and sphingolipid. MATERIALS AND METHODS: To investigate this field, we applied a high-coverage targeted lipidomics approach of VAT and SAT in male C57BL/6J mice to compare the basal level of their lipid profiles. Applying microarray and quantitative real-time polymerase chain reaction, we analyzed the transcriptome of twodepot-specific WAT and verified the differences in individual genes. KEY FINDINGS: In total, 342 lipid species from 19 lipid classes were identified. Our results showed the composition of TAG and FFA were different in length of chain and saturation. Interestingly, low abundance phospholipid, sphingolipid and cardiolipin were significantly higher in SAT. Lipid correlation network analysis vindicated that TAG and phospholipid formed distinct subnet and had more connections with other lipid species. Enriched ontology analysis of gene screened from LIPID MAPS and microarray suggested the differences were mainly involved in lipid metabolism, insulin resistance and inflammatory response. SIGNIFICANCE: Our comprehensive lipidomics and transcriptomics analyses revealed differences in lipid composition and lipid metabolism of two depot-specific WAT, which would offer new insights into the investigation of heterogeneity of visceral and subcutaneous white adipose tissue.


Assuntos
Tecido Adiposo Branco/metabolismo , Gordura Intra-Abdominal/metabolismo , Lipidômica , Gordura Subcutânea/metabolismo , Transcriptoma , Tecido Adiposo Branco/química , Animais , Cardiolipinas/análise , Cardiolipinas/metabolismo , Ceramidas/análise , Ceramidas/metabolismo , Ácidos Graxos/análise , Ácidos Graxos/metabolismo , Glicerídeos/análise , Glicerídeos/metabolismo , Gordura Intra-Abdominal/química , Metabolismo dos Lipídeos , Lipídeos/análise , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosfolipídeos/análise , Fosfolipídeos/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Gordura Subcutânea/química
6.
Liver Int ; 40(5): 1211-1223, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32077551

RESUMO

BACKGROUND AND AIMS: Heat shock factor (HSF4) plays a vital role in carcinogenesis and tumour progression. However, its clinical significance implications in hepatocellular carcinoma (HCC) remained elusive. METHODS: RT-PCR and western blot were used to detect the HSF4 expression levels in HCC cells and tissues. Immunohistochemistry staining was performed on a tissue microarray containing 104 HCC patients received radical resection. In vitro effects of HSF4 on proliferation, migration and invasion were determined by colony formation and transwell assays in HCCLM3, Huh7, MHCC97L and SMMC7721 cells. Epithelial-mesenchymal transition (EMT) was identified by RT-PCR, WB and immunofluorescence in HCCLM3 and MHCC97L cells. AKT pathway activation was detected by WB and dual luciferase report system in HCCLM3 and MHCC97L cells. RESULTS: HSF4 expression was higher in primary HCC tissues derived from recurrent patients, and positively correlated with invasiveness potentials of cell lines. Clinically, patients with high HSF4 expression had significant poorer prognosis. In vitro experiments showed HSF4 silencing inhibited HCC cell proliferation, migration and invasion, whereas HSF4 overexpression had inverse effects. Moreover, silence of HSF4 induced an epithelial-like phenotype, whereas the overexpression of HSF4 resulted in a mesenchymal-like phenotype in HCC by activating AKT pathway. Further experiments showed that HSF4 could activate AKT pathway in a hypoxia-inducible factor-1α (HIF-1α) dependent, but transforming growth factor-ß (TGF-ß) independent manner. CONCLUSIONS: HSF4 is upregulated in HCC, resulting in greater proliferation, migration and invasion capacities. Moreover, high HSF4 expression is a promising predictive indicator of poor outcome after radical resection. HSF4 may promote aggressive tumour behaviour by enhancing EMT through activating AKT pathway in a HIF1α-dependent manner.

7.
FEBS Open Bio ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31898405

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid tumors in the digestive system. A greater understanding of the pathogenesis of PDAC may facilitate the search for new therapeutic targets. Guanine nucleotide-binding protein subunit gamma-12 (GNG12) belongs to the G protein family and participates in the modulation of the inflammatory signaling cascade. However, the cancer-related function and clinical relevance of GNG12 in PDAC have not previously been reported. Here, we investigated the clinical significance of GNG12 in PDAC using the Oncomine web tool, the gene expression profiling interactive analysis tool and tissue microarray (TMA). GNG12 expression was observed to be higher in PDAC patient specimens than in nontumor pancreatic tissues, and high expression of GNG12 was associated with poor prognosis. We subsequently show that GNG12 promotes pancreatic cancer cell growth in vivo and in vitro, as evaluated using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assays, colony formation assays and a xenograft mouse model. Furthermore, our results suggest that GNG12 activates nuclear factor-κB signaling and modulates the immune response. Collectively, our findings suggest that GNG12 may be suitable as a new prognosis-related biomarker and a promising target for treatment of pancreatic cancer.

8.
Biophys J ; 118(3): 729-741, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-31928764

RESUMO

The aim of this study was to characterize cupular deformation by calculating the degree of cupular expansion and cupular deflection using a finite element model of bilateral human semicircular canals (SCCs). The results showed that cupular deflection responses were consistent with Ewald's II law, whereas each pair of bilateral cupulae simultaneously expanded or compressed to the same degree. In addition, both the degree of cupular expansion and cupular deflection can be expressed as the solution of forced oscillation during head sinusoidal rotation, and the amplitude of cupular expansion was approximately two times greater than that of cupular deflection. Regarding the amplitude frequency and phase frequency characteristics, the amplitude ratios among the horizontal SCC, the anterior SCC, and the posterior SCC cupular expansion was constant at 1:0.82:1.62, and the phase differences among them were constant at 0 or 180° at the frequencies of 0.5-6 Hz. However, both the amplitude ratio and the phase differences of the cupular deflection increased nonlinearly with the increase of frequency and tended to be constant at the frequency band between 2 and 6 Hz. The results indicate that the responses of cupular expansion might only be related to the mass and rigidity of three cupulae and the endolymph, but the responses of cupular deflection are related to the mass, rigidity, or damping of them, and these physical properties would be affected by vestibular dysfunction. Therefore, both the degree of cupular expansion and cupular deflection should be considered important mechanical variables for induced neural signals as these variables provide a better understanding of the SCCs system's role in the vestibulo-ocular reflex during the clinical rotating chair test and the vestibular autorotation test. Such a numerical model can be further built to provide a useful theoretical approach for exploring the biomechanical nature underlying vestibular dysfunction.

9.
Talanta ; 208: 120484, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816727

RESUMO

Gas embolism is the abnormal emergence of bubble in the vascular system, which can induce local ischemic symptoms. For studying the mechanism underlying gas embolism and revealing local ischemic diseases information, novel technique for analyzing cells response to bubble contact with high controllability is highly desired. In this paper, we present an integrated microfluidic device for the precise generation and control of microbubble based on the gas permeability of polydimethysiloxane (PDMS) to study the effect of bubble's mechanical contact on cells. Cell viability analysis demonstrated that short-term (<15 min) bubble contact was generally non-lethal to cultured endothelial cells. The significant increase in intracellular calcium of the microbubble-contacted cells and cell-to-cell propagation of calcium signal in the adjacent cells were observed during the process of bubble expansion. In addition, the analysis of intercellular calcium signal in the cells treated with suramin and octanol revealed that cell-released small nucleotides and gap junction played an important role in regulating the propagation of calcium wave triggered by bubble contact. Thus, our microfluidic method provides an effective platform for studying the effect of gas embolism on cultured adherent cells and can be further needed for anti-embolism drugs test.

10.
J Neurosci Res ; 98(2): 384-403, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31407399

RESUMO

The cAMP-dependent protein kinase A family (PKAs), protein kinase C family (PKCs), and Src family kinases (SFKs) are found to play important roles in pain hypersensitivity. However, more detailed investigations are still needed in order to understand the mechanisms underlying the actions of PKAs, PKCs, and SFKs. Neurons in the hypothalamic arcuate nucleus (ARC) are found to be involved in the regulation of pain hypersensitivity. Here we report that the action potential (AP) firing activity of ARC neurons in culture was up-regulated by application of the adenylate cyclase activator forskolin or the PKC activator PMA, and that the forskolin or PMA application-induced up-regulation of AP firing activity could be blocked by pre-application of the SFK inhibitor PP2. SFK activation also up-regulated the AP firing activity and this effect could be prevented by pre-application of the inhibitors of PKCs, but not of PKAs. Furthermore, we identified that forskolin or PMA application caused increases in the phosphorylation not only in PKAs at T197 or PKCs at S660 and PKCα/ßII at T638/641, but also in SFKs at Y416. The forskolin or PMA application-induced increase in the phosphorylation of PKAs or PKCs was not affected by pre-treatment with PP2. The regulations of the SFK and AP firing activities by PKCs were independent upon the translocation of either PKCα or PKCßII. Thus, it is demonstrated that PKAs may act as an upstream factor(s) to enhance SFKs while PKCs and SFKs interact reciprocally, and thereby up-regulate the AP firing activity in hypothalamic ARC neurons.

11.
Opt Express ; 27(19): 27229-27241, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31674588

RESUMO

An accurate model for the silicon refractive index including its temperature and wavelength dependence is critically important for many disciplines of science and technology. Currently, such a model for temperatures above 22°C in the optical communication bands is not available. The temperature dependence in the spectral response of integrated echelle grating filters made in silicon-on-insulator is solely determined by the optical properties of the slab waveguide, making it largely immune to dimensional uncertainties. This feature renders the echelle filters a reliable tool to evaluate the thermo-optic properties of silicon. Here we investigate the temperature dependence of silicon echelle filters for the wavelength range of both O and C bands, measured between 22°C to 80°C. We show that if a constant thermo-optic coefficient of silicon is assumed for each band, as is common in the literature, the predictions show an underestimate of up to 10% in the temperature-induced channel wavelength shift. We propose and assess a model of silicon refractive index that encompasses both the wavelength and temperature dependence of its thermo-optic coefficients. We start from literature data for bulk silicon and further refine the model using the echelle filter measurement results. This model is validated through accurate predictions of device channel wavelengths and their temperature dependence, including the quadratic term, over a wide wavelength and temperature range. This work also demonstrates a new high-precision method for characterizing the optical properties of a variety of materials.

12.
PLoS One ; 14(11): e0225214, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31714929

RESUMO

Dysfunctional mitochondria have been implicated in aging and age-related disorders such as Parkinson's diseases (PD). We previously showed that pink1 and parkin, two familial PD genes, function in a linear pathway to maintain mitochondrial integrity and function. Studies of mammalian cell lines also suggest that these genes regulate mitochondrial autophagy(mitophagy). Overexpressing Parkin promotes proteostasis and function of aged muscles both in fruit flies and mice, and recent studies also indicated that mitochondrial ubiquitination are accumulated in aged muscles. However, the underlying mechanisms for pink1 and parkin mediated mitophagy on longevity is not fully understood. Here, we found that mitochondrial ubiquitination increased in indirect flight muscles (IFMs) in an age-dependent manner. Overexpression of pink1 or parkin in IFMs can abolish mitochondrial ubiquitination, restore ATP level and extend lifespan, while blocking autophagy via ATG1 knock-down suppress these effects in aged IFMs. Taken together, these results show that pink1/parkin promotes mitophagy of mitochondrial ubiquitination in aged muscles and extend lifespan in an Atg1-dependent manner. Our study provides physiological evidence that mitophagy of mitochondrial ubiquitination mediated by PINK1/ Parkin is crucial for muscle function and highlights the role of mitophagy in the pathogenesis of chronic diseases like PD.

13.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(5): 629-634, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31762229

RESUMO

OBJECTIVE: To establish a way for screening Mycobacterium mutants through adding the screening markers into pJV53. METHODS: The sucrose counter selection gene SacB and mutant hygromycin-resistant gene hygS were inserted into pJV53; The recovery of the hygromycin-resistance indicated the successful homologous recombination in Mycobacterium smegmatis (Ms), which could serve as mutant screening marker; The sucrose counter selection could be used to screen the plasmid-free mutants. RESULTS: The recombinant plasmid pJV53-SacB-hygS were successfully constructed. The rifampin-resistant rpoB D516Y and rpoB H526Q mutants and MSMEG_4487 G188A mutant were efficiently screened out. All mutants had shed the plasmid successfully. CONCLUSION: pJV53-SacB-hygS can efficiently contribute to construct and screen the mutants and to get the mutants shedding the plasmid self, which has high value of extensive application; the D516Y and H526Q mutations in gene rpoB of Mycobacterium tuberculosis contribute to its rifampin-resistance.


Assuntos
Farmacorresistência Bacteriana/genética , Recombinação Homóloga , Mycobacterium smegmatis/genética , Mycobacterium tuberculosis/genética , Proteínas de Bactérias/genética , RNA Polimerases Dirigidas por DNA/genética , Testes de Sensibilidade Microbiana , Mutação , Mycobacterium tuberculosis/efeitos dos fármacos , Plasmídeos/genética , Rifampina/farmacologia
14.
Pharmacology ; : 1-16, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31630149

RESUMO

Nitroglycerin (NTG), a nitric oxide-donating drug, may increase tumor blood flow and consequently increase cancer drug delivery to tumor cells. Thymidylate synthase (TS) is an essential enzyme for the de novo synthesis of deoxythymidine monophosphate; we had found that knocking down the expression of TS sensitizes lung cancer cells to cisplatin-induced cytotoxicity. However, whether NTG and cisplatin could induce synergistic cytotoxicity in nonsmall cell lung cancer (NSCLC) cells through modulating TS expression is unknown. In this study, NTG decreased TS expression in an AKT, also known as Protein kinase B (PKB) inactivation dependent manner in human lung adenocarcinoma A549 and squamous cell carcinoma H1703 cells. Enhancement of AKT activity by transfection with constitutive active AKT vectors increased the TS expression level as well as the cell survival pretreated by NTG. Moreover, NTG synergistically enhanced cytotoxicity and cell growth inhibition by cisplatin treatment in NSCLC cells, which were associated with downregulation of TS expression and inactivation of AKT in A549 and H1703 cells. Together, these results may provide a rationale to combine NTG with cisplatin-based chemotherapy to enhance the therapeutic effect for lung cancer in the future.

15.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(3): 291-297, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31631592

RESUMO

Objective: To explore the biological characteristics of the esterase LipR encoded by Mycobacterium tuberculosis (MTB) Rv3084 and its immunomodulatory function in vivo. Methods: The LipR gene was amplified from MTB H37Rv strain to construct recombinant expression plasmid. After sequencing, the recombinant plasmid was transformed into E. coli for expression and purification of LipR protein. The expressed protein was confirmed with Western blot assay. The hydrolyzing activity of LipR was detected and the factors affecting LipR enzyme activity were analyzed. Mice were intramuscularly injected with 0.1 mL (containing plasmid DNA 100 µg) recombinant eukaryotic plasmid three times (day 1, 8, and 15); seven days after the last injection, the mice were executed, and the lung and spleen were taken for cytokine detection. Results: The recombinant expression plasmid was successfully constructed and it was found that LipR protein was mainly expressed in the form of inclusion bodies in E. coli with the relative molecular mass of about 33×10 3. LipR was demonstrated as an alkaline eurythermic esterase, due to the preference of hydrolyzing short carbon chain esters with optimal hydrolyzing activity on pNP-acetate (pNPA, C2) and the capability in tolerance of high pH and temperature; in the presence of different detergents or metal ions, the activity of LipR hydrolyzing pNP-butyrate (pNPB, C4) was inhibited to some extent. In the mouse model, it was found that LipR could inhibit the secretion of interferon-γ (IFN- γ) and interleukin-2 (IL-2), but to stimulate the secretion of IL-10. Conclusion: The esterase LipR may be one of the esterases help M. tuberculosis withstand harsh environment inside the host in collaboration, and simultaneously act as an immune modulator to inhibit the secretion of pro-inflammatory cytokines and consequently impact the killing effect of host immune system against M. tuberculosis.


Assuntos
Proteínas de Bactérias/metabolismo , Esterases/metabolismo , Interferon gama/imunologia , Interleucina-10/imunologia , Interleucina-2/imunologia , Mycobacterium tuberculosis/enzimologia , Animais , Camundongos
16.
Biomolecules ; 9(9)2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31484405

RESUMO

BACKGROUND: White adipose tissue (WAT) browning confers beneficial effects on metabolic diseases. However, visceral adipose tissue (VAT) is not as susceptible to browning as subcutaneous adipose tissue (SAT). AIM: Interpreting the heterogeneity of VAT and SAT in brown remodeling and provide promising lipid targets to promote WAT browning. METHODS: We first investigated the effects of ß3-adrenergic stimulation by CL316,243 on systemic metabolism. Then, high-coverage targeted lipidomics approach with multiple reaction monitoring (MRM) was utilized to provide extensive detection of lipid metabolites in VAT and SAT. RESULTS: CL316,243 notably ameliorated the systemic metabolism and induced brown remodeling of SAT but browning resistance of VAT. Comprehensive lipidomics analysis revealed browning heterogeneity of VAT and SAT with more dramatic alteration of lipid classes and species in VAT rather than SAT, though VAT is resistant to browning. Adrenergic stimulation differentially affected glycerides content in VAT and SAT and boosted the abundance of more glycerophospholipids species in VAT than in SAT. Besides, CL316,243 increased sphingolipids in VAT without changes in SAT, meanwhile, elevated cardiolipin species more prominently in VAT than in SAT. CONCLUSIONS: We demonstrated the browning heterogeneity of WAT and identified potential lipid biomarkers which may provide lipid targets for overcoming VAT browning resistance.

17.
Talanta ; 205: 120101, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31450477

RESUMO

Pseudo-graphite from the University of Idaho Thermolyzed Asphalt Reaction also known as GUITAR is a new form of carbon. It shares morphological features with graphites, including basal and edge planes. Unlike graphites and other sp2-hybridized carbons, GUITAR has fast heterogeneous electron transfer across its basal planes and resistance to corrosion similar to boron-doped diamond electrodes. In this contribution GUITAR electrodes were examined as sensors for aqueous free chlorine (HOCl and OCl-) at pH 7.0 with cyclic voltammetric (CV) and chronoamperometric (CA) methods. Using CV at 50 mV s-1 GUITAR has a limit of detection of 1.0 µmol L-1, linear range of 0-5,000 µmol L-1, sensitivity of 215.8 µA L mmol-1 cm-2 and a signal stability of 4 days in constant exposure to 1 mmol L-1 free chlorine in pH 7.0, 0.1 mol L-1 phosphate buffer system. After 7 days of exposure GUITAR electrodes lost 37% of the former sensitivity, which was recovered by an in-situ regeneration procedure. The common aqueous ions, Ca2+, Na+, NO3-, SO42-, Cl-, CO32- and dissolved oxygen did not affect the response of the GUITAR-based sensor. The combination of limit of detection, linear range, sensitivity, sensor lifetime and its relative lack of interferences indicate that GUITAR is one of the best performers in free chlorine sensors.

18.
J Cancer ; 10(15): 3533-3542, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31293658

RESUMO

The role of the human cervical cancer oncogene (HCCR-1) in the development of various tumors has been elucidated; however, its expression and function in gastric cancer remains largely unknown. Accordingly, the expression of HCCR-1 and epidermal growth factor (EGF) were detected in paired gastric cancer tissues and cell lines by western blotting (WB) and immunohistochemistry (IHC). Furthermore, the correlations between HCCR-1 expression in 209 gastric cancer tissues and the clinicopathological features and disease prognosis were analyzed. A stable HCCR-1 overexpression cell line was established, and the influence of increased HCCR-1 expression on the growth of gastric cancer cells was observed in vivo and in vitro. The expression of HCCR-1 generally increased in gastric cancer tissues. Further, increased HCCR-1 expression in gastric cancer tissues was associated with tumor T stage and was an independent factor that influenced poor postoperative prognosis in gastric cancer patients. A positive correlation was also detected between the expression of EGF and HCCR-1 in a time- and dose-dependent manner. The overexpression of HCCR-1 might enhance the growth rate of gastric cancer cells in vitro, increase the number of colony forming units, and promote the growth, volume, and weight of subcutaneous tumors in nude mice. In conclusion, HCCR-1 is a gastric cancer oncogene, and its increased expression plays a critical role in the occurrence and development of gastric cancer. Hence, HCCR-1 could serve as a valuable marker for the postoperative prognostic assessment of gastric cancer patients.

20.
Ann Hum Biol ; : 1-6, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31208219

RESUMO

Background: Previous studies have suggested that the human Y-chromosome haplogroup Q1a1a-M120, a widespread paternal lineage in East Asian populations, originated in South Siberia. However, much uncertainty remains regarding the origin, diversification, and expansion of this paternal lineage. Aim: To explore the origin and diffusion of paternal Q-M120 lineages in East Asia. Subjects and methods: The authors generated 26 new Y chromosome sequences of Q-M120 males and co-analysed 45 Y chromosome sequences of this haplogroup. A highly-revised phylogenetic tree of haplogroup Q-M120 with age estimates was reconstructed. Additionally, a comprehensive phylogeographic analysis of this lineage was performed including 15,007 samples from 440 populations in eastern Eurasia. Results: An ancient connection of this lineage with populations in Siberia was revealed. However, this paternal lineage experienced an in-situ expansion between 5000 and 3000 years ago in northwestern China. Ancient populations with high frequencies of Q-M120 were involved in the formation of ancient Huaxia populations before 2000 years ago; this haplogroup eventually became one of the founding paternal lineages of modern Han populations. Conclusion: This study provides a clear pattern of the origin and diffusion process of haplogroup Q1a1a-M120, as well as the role of this paternal lineage during the formation of ancient Huaxia populations and modern Han populations.

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