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1.
Eur J Pharmacol ; : 174260, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34144026

RESUMO

Sphingosine-1-phosphate (S1P)/S1P receptor 1 signaling exerts cardioprotective effects including inhibition of myocyte apoptosis. However, little is known about the effect of S1P treatment on myocyte autophagy after myocardial infarction (MI). In the present study, we tested the hypothesis that S1P induces myocyte autophagy through inhibition of the mammalian target of rapamycin (mTOR), leading to improvement of left ventricular (LV) function after MI. Sprague-Dawley rats underwent MI or sham operation. The animals were randomized to receive S1P (50 ug/kg/day, i.p.) or placebo for one week. H9C2 cardiomyocytes cultured in serum- and glucose-deficient medium were treated with or without S1P for 3 h. MI rats exhibited an increase in LV end-diastolic dimension (EDD) and decreases in LV fractional shortening (FS) and the maximal rate of LV pressure rise (+dP/dt). S1P treatment attenuated the increase in LV EDD and decreases in LV FS and +dP/dt. In the MI placebo group, the LC3 II/I ratio, a marker of autophagy, was increased, and increased further by S1P treatment. S1P also enhanced the autophagy-related proteins Atg4b and Atg5 after MI. Similarly, in cultured cardiomyocytes, autophagy was increased under glucose and serum deprivation, and increased further by S1P treatment. The effect of S1P on myocyte autophagy was associated with mTOR inhibition after MI or in cultured cardiomyocytes under glucose and serum deprivation. S1P treatment prevents LV remodeling, enhances myocyte autophagy and inhibits mTOR activity after MI. These findings suggest that S1P treatment induces myocyte autophagy through mTOR inhibition, leading to the attenuation of LV dysfunction after MI.

2.
J Chromatogr Sci ; 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34136906

RESUMO

An efficient method for simultaneous extraction, purification and determination of six lignans in Schisandra chinensis Baill was developed by employing matrix solid-phase dispersion (MSPD) extraction followed by HPLC-UV determination analysis. Several sorbent and desorption solvent that affected the extraction yield of lignans were investigated; neutral alumina and absolute ethanol were selected as the best dispersing material and desorption agent, respectively. Other extraction conditions for MSPD were optimized as follows: 1:2 of S. chinensis raw material to neutral aluminum oxide mass ratio, 1:30 (g/mL) of sample to absolute ethanol, 2.5 h of desorption time and 50°C of desorption temperature. Under the above conditions, the total extraction yield for six lignans have reached (16.99 ± 0.33) x 103 mg/kg with a higher content of 6.88 ± 0.25% in the extracts. Comparative studies were explored by conducting other six extraction approaches including Soxhlet extraction, heat reflux extraction, smashing tissue extraction, microwave-assisted extraction, ultrasonic-assisted extraction and ultrasonic-microwave synergistic extraction. Results showed MSPD technique not only improved the extraction yield, but also improved the purity of lignans, it can be generalized to more extraction of natural compounds. In addition, the validated HPLC-UV method had been successfully applied to analysis of lignans from 10 real S. chinensis samples.

3.
Bioengineered ; 12(1): 1457-1470, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33949285

RESUMO

Pediatric sepsis is a great threat to death worldwide. However, the pathogenesis has not been clearly understood until now in sepsis. This study identified differentially expressed mRNAs and lncRNAs based on Gene Expression Omnibus (GEO) database. And the weighted gene co-expression network analysis (WGCNA) was performed to explore co-expression modules associated with pediatric sepsis. Then, Gene Ontology (GO), KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway, mRNA­lncRNA and mRNA­lncRNA-pathway co-expression network analysis was conducted in selected significant module. A total of 1941 mRNAs and 225 lncRNAs were used to conduct WGCNA. And turquoise module was selected as a significant module that was associated with particular traits. The mRNAs functions associated with many vital processes were also shown by GO and KEGG pathway analysis in the turquoise module. Finally, 15 mRNAs (MAPK14, ITGAM, HK3, ALOX5, CR1, HCK, NCF4, PYGL, FLOT1, CARD6, NLRC4, SH3GLB1, PGS1, RAB31, LTB4R) and 4 lncRNAs (GSEC, NONHSAT160878.1, XR_926068.1 and RARA-AS1) were selected as hub genes in mRNA­lncRNA-Pathway co-expression network. We identified 15 mRNAs and 4 lncRNAs as diagnostic markers, which have potential functions in pediatric sepsis. Our study provides more directions to study the molecular mechanism of pediatric sepsis.Abbreviations: mRNA: messenger RNA; lncRNA: long noncoding RNAs; GEO: Gene Expression Omnibus; WGCNA: weighted gene co-expression network analysis; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; SIRS: systemic inflammatory response syndrome; TOM: topological overlap measure; BP: biological process; MF: molecular function; CC: cellular component; ROC: receiver operating characteristic curve; AUC: area under curve; MAPK14: Mitogen-activated protein kinase 14; ALI: acute lung injury; ITGAM: Integrin subunit alpha M; HK3: Hexokinase 3; LPS: lipopolysaccharide; 5-LO: 5-lipoxygenase; LTs: leukotrienes; LTB4R: leukotriene B4 receptor.

4.
BMC Genomics ; 22(1): 328, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952209

RESUMO

BACKGROUND: Fatty liver has become a main problem that causes huge economic losses in many aquaculture modes. It is a common physiological or pathological phenomenon in aquaculture, but the causes and occurring mechanism are remaining enigmatic. METHODS: Each three liver samples from the control group of allogynogenetic gibel carp with normal liver and the overfeeding group with fatty liver were collected randomly for the detailed comparison of histological structure, lipid accumulation, transcriptomic profile, latent pathway identification analysis (LPIA), marker gene expression, and hepatocyte mitochondria analyses. RESULTS: Compared to normal liver, larger hepatocytes and more lipid accumulation were observed in fatty liver. Transcriptomic analysis between fatty liver and normal liver showed a totally different transcriptional trajectory. GO terms and KEGG pathways analyses revealed several enriched pathways in fatty liver, such as lipid biosynthesis, degradation accumulation, peroxidation, or metabolism and redox balance activities. LPIA identified an activated ferroptosis pathway in the fatty liver. qPCR analysis confirmed that gpx4, a negative regulator of ferroptosis, was significantly downregulated while the other three positively regulated marker genes, such as acsl4, tfr1 and gcl, were upregulated in fatty liver. Moreover, the hepatocytes of fatty liver had more condensed mitochondria and some of their outer membranes were almost ruptured. CONCLUSIONS: We reveal an association between ferroptosis and fish fatty liver for the first time, suggesting that ferroptosis might be activated in liver fatty. Therefore, the current study provides a clue for future studies on fish fatty liver problems.


Assuntos
Carpas , Fígado Gorduroso , Ferroptose , Animais , Fígado Gorduroso/genética , Transcriptoma
5.
Orthop Surg ; 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33973714

RESUMO

OBJECTIVES: Measure and systematically evaluate the distribution of microhardness in the human skeleton. METHODS: Three fresh corpses were obtained, aged 62 (male), 45 (female), and 58 years (male). Soft tissues were removed, and all axial and unilateral appendicular bones were freshly harvested. All three skeletons were examined by X-ray and computed tomography (CT) to exclude skeletal pathology. Only bones from donors with no known skeletal pathology were included in the study. Axial and unilateral appendicular skeleton bones from each of the three donors were obtained, except for ear ossicles, hyoid bone, tailbone, and 14 phalanges of the foot, for which samples were difficult to obtain. Precision bone specimens with a thickness of 3 mm, which were cut with a Buehler IsoMet 11-1280-250 low-speed diamond saw (Buehler, USA), were obtained from all important anatomic sites in a direction perpendicular to the mechanical axis of each bone. Micro-indentation (the Vickers hardness test) was performed on the surface of each specimen using a microhardness tester with a diamond indenter. Hardness value (HV) was computed for each indentation. Each bone specimen was divided into several regions of interest. Indentations were carefully made and computed. Then we analyzed the data to identify hardness distribution rules at different anatomic sites. RESULTS: In total, 5360 indentations were made in 1072 regions of interest in each donor. Hardness of the axial and appendicular bones were all inhomogeneous depending on the anatomic sites, but the distribution of microhardness followed certain rules. The mean hardness value ranged from 24.46 HV (HV = hardness value, kgf/mm2 ) for the sacrum to 53.20 HV for the shaft of the tibia. The diaphysis was harder than the metaphysis, and the proximal and distal epiphysis had lower values (8.85%- 40.39%) than the diaphysis. Among the long bone diaphyses, the tibia cortical bone (51.20 HV) was the hardest, harder than the humerus (47.25 HV), the ulna (43.26 HV), the radius (42.54 HV), and the femur (47.53 HV). However, in some anatomic sites such as the lumbar vertebra (cortical bone 32.86 HV, cancellous bone 31.25 HV), the cortical shells were sometimes not harder than the internal cancellous bones. The lumbar vertebra (32.86 HV) was harder than the cervical vertebra (28.51 HV) and the thoracic vertebra (29.01 HV). CONCLUSIONS: The distribution of microhardness in the human skeleton follows certain rules. These distribution rules could be used to predict the mechanical properties of bone and progress in this field could provide data for the basis of a new three-dimensional printing technique, which may lead to new perspectives for custom-made implants.

6.
Nanoscale ; 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34013941

RESUMO

Water electrolysis is a significant alternative technique to produce clean hydrogen fuel in order to replace environmentally destructive fossil fuel combustion. However, the sluggish oxygen evolution kinetics makes this process vulnerable as it requires relatively high overpotentials. Hence, significantly effective electrocatalysts are necessary to access the water-oxidation process at a low overpotential to make this process industrially viable. Therefore, in order to reduce the energy barrier, we developed bimetallic CoSe2-FeSe2 heteronanoparticles along the carbon nanotube network (CoSe2-FeSe2/CNT) via a facile selenization strategy. Due to the unique assembly of highly conductive nanoparticles along the CNT network, the CoSe2-FeSe2/CNT displays an exceptionally good oxygen evolution (OER) activity; it requires 248 mV overpotential to reach a current density of 10 mA cm-2 (η10) with an ultra-low Tafel slope of 36 mV dec-1 and displays an overpotential of 1.59 V (η10) in the full water-splitting catalysis with the commercial Pt/C cathode. The high OER activity of CoSe2-FeSe2/CNT over the monometallic CoSe2/CNT and FeSe2/CNT electrocatalysts approve the synergistic interactions. Therefore, the superior performance is possibly ascribed to the unique porous nanoarchitecture and the strong coupling interactions between CoSe2 and FeSe2 heteronanoparticles on the conductive network. This study introduces an innovative approach to rationally design and fabricate cost-effective and highly proficient electrocatalysts for boosted OER performance.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33837431

RESUMO

BACKGROUND: Conclusions remain controversial between the consumption of sugar and artificially sweetened beverages (SSBs and ASBs) and mortality. METHODS: We systematically searched the PubMed, Embase, Cochrane Library and Web of Science databases from their inception date to 1st January 2020, prospective cohort studies researching the mortality risk and SSBs or ASBs consumption were included. Random effects meta-analyses and dose-response analyses were performed to measure the association. Subgroup analyses and sensitivity analyses were further performed to explore the source of heterogeneity. Publication bias was assessed by Funnel plots and Egger's regression test. RESULTS: Across all 15 cohorts, 1211 470 participants were included. High SSB consumption was associated with a higher risk of all-cause mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.06-1.19, P < 0.001; and cardiovascular disease [CVD] mortality [HR 1.20, 95% CI, 1.05-1.38, P < 0.001]), and high ASBs consumption showed similar result (HR 1.12, 95% CI, 1.04-1.21, P = 0.001 for all-cause mortality and HR 1.23, 95% CI, 1.00-1.50, P = 0.049 for CVD mortality), both showed a linear dose-response relationship. CONCLUSIONS: High consumption of both ASBs and SSBs showed significant associations with a higher risk of CVD mortality and all-cause mortality. This information may provide ideas for decreasing the global burden of diseases by reducing sweetened beverage intake.

8.
Small ; : e2100460, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33891797

RESUMO

The slow redox kinetics during cycling process and the serious shuttle effect caused by the solubility of lithium polysulfides (LiPSs) dramatically hinder the practical application of Li-S batteries. Herein, a facile and scalable spray-drying strategy is presented to construct conductive polar Mo2 C quantum dots-decorated carbon nanotube (CNT) networks (MCN) as an efficient absorbent and electrocatalyst for Li-S batteries. The results reveal that the MCN/S electrode exhibits a high specific capacity of 1303.3 mAh g-1 at 0.2 C, and ultrastable cycling stability with decay of 0.019% per cycle even at 1 C. Theoretical simulation uncovers that Mo2 C exhibits much stronger binding energies for S8 and Li2 Sn . The energy barrier for the conversion between Li2 S4 and Li2 S2 decreases from 1.02 to 0.72 eV when hybriding with Mo2 C. Furthermore, in situ discharge/charge-dependent Raman spectroscopy shows that long-chain Li2 S8 configuration is generated via S8 ring opening near the first plateaus at ≈2.36 V versus Li/Li+ and the S6 2- configuration in CNT/S electrode is maintained below the potential of ≈2.30 V versus Li/Li+ , indicating that the shuttle of soluble LiPSs happens during the whole discharge process. This work provides deep insights into the polar nanoarchitecture design and scalable fabrication for advanced Li-S batteries.

9.
Ann Palliat Med ; 10(3): 3039-3049, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33849094

RESUMO

BACKGROUND: This study aimed to estimate peripheral blood lymphocyte subsets and programmed death receptor-1 positive (PD-1+) proportions of T cells, and their impact on progression free survival (PFS) and radiological response in lung cancer. METHODS: From May 2018 to April 2020, 34patients of the Henan Tumor Hospital who were diagnosed with advanced lung cancer were recruited to this study. Peripheral blood lymphocyte subsets and PD-1+ proportions of T cells were assessed by flow cytometry before and after treatment with immune checkpoint inhibitors (ICIs). The associations among these parameters, and PFS and clinical response were estimated by survival analysis and Fishers' exact test, respectively. RESULTS: Several lymphocyte variables and biomarkers were found to be correlated with PFS and tumor response, as assessed using the Response Evaluation Criteria in Solid Tumors (RECIST). In all 34 lung cancer participants and a subgroup of 28 participants with non-small cell lung cancer (NSCLC), higher levels of natural killer (NK) cells and higher CD4+/CD8+ cell ratios before the ICIs treatment were associated with longer PFS. Moreover, CD4+ T cells were significantly correlated with radiological response in all 34 lung cancer participants. Of the 28 NSCLC participants, those with higher levels of CD4+ T cells, CD4+/CD8+ cell ratios, absolute numbers of NK cells, and lower levels of regulatory T cells (Tregs)before treatment had better tumor response. After 2 cycles of combined ICIs treatment, both the absolute numbers of CD4+ T cells and CD45+ lymphocytes were statistically associated with PFS after being adjusted for gender and neutrophil-lymphocyte ratio (NLR) [hazard ratio (HR) =0.23, P=0.015; HR=0.30, P=0.032, respectively]. The absolute numbers of CD45+, CD3+, and CD4+ T lymphocytes were associated with radiological response treated by ICIs (P=0.038). CONCLUSIONS: Our results suggested that the absolute number of NK cells and CD4+/CD8+ cells ratio before treatment could predict longer PFS and better radiological response in lung cancer patients treated with ICIs combination therapy. In addition, Tregs, as well as the other parameters in lymphocyte subsets, may also predict response.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares/tratamento farmacológico , Subpopulações de Linfócitos , Análise de Sobrevida
10.
Artigo em Inglês | MEDLINE | ID: mdl-33890784

RESUMO

It is still a big challenge to effectively suppress dendrite growth, which increases the safety and life of lithium-metal-based high energy/power density batteries. To address such issues, herein we design and fabricate a lithiophilic VN@N-rGO as a multifunctional layer on commercial polypropylene (PP) separator, which is constructed by a thin N-rGO nanosheet-wrapped VN nanosphere with a uniform pore distribution, relatively high lithium ionic conductivity, excellent electrolyte wettability, additional lithium-ion diffusion pathways, high mechanical strength, and reliable thermal stability, which are beneficial to regulate the interfacial lithium ionic flux, resulting in the formation of a stable and homogeneous current density distribution on Li-metal electrodes and hard modified separators that can resist dendrites piercing. Consequently, the growth of Li dendrite is effectively suppressed, and the cycle stability of lithium-metal batteries is significantly improved. In addition, even at a high current density of 10 mA cm-2 and cutoff areal capacity of 5 mAh cm-2, the Li|Li symmetric batteries with VN@N-rGO/PP separators still work very well even over 2500 h, exhibiting ultrahigh cycling stability. This work presents rational design ideas and a facile fabrication strategy of a lithiophilic 3D porous multifunctional interlayer for dendrite-free and ultrastable lithium-metal-based batteries.

11.
Food Microbiol ; 98: 103766, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33875202

RESUMO

Daqu, a brick-shaped product spontaneously fermented under an open environment, has been regarded as the starter of fermentation, raw enzyme preparation and raw materials for baijiu production. However, its contribution in baijiu fermentation has not been fully elaborated yet. Here, the effects of daqu microbiota on baijiu fermentation were investigated under both field-scale and lab-scale conditions. In field-scale baijiu fermentation, the dominant daqu microbes (average relative abundance>10.0%), including unclassified_Leuconostocaceae, Thermoascus, and Thermomyces, tended to dominate the early stage (0-7 d). However, the rare daqu microbes (average relative abundance <0.1%, e.g., Kazachstania) tended to dominate the middle and late stages (11-40 d). In addition, some genera showed differences in species diversity between daqu and fermented grains. The average relative abundance of Lactobacillus was over 75% during baijiu fermentation, and most of them were affiliated with Lactobacillus acetotolerans, while Lactobacillus crustorum dominated the Lactobacillus OTUs in daqu. The similar patterns were also observed during lab-scale baijiu fermentation. The results of function prediction showed the enriched metabolic pathways were associated with glycolysis and long-chain fatty acid esters in baijiu fermentation. These results improved the understanding of daqu microbiota function during baijiu fermentation and provided a basic theory to support the regulation of baijiu production.


Assuntos
Bebidas Alcoólicas/microbiologia , Lactobacillus/isolamento & purificação , Lactobacillus/metabolismo , Microbiota , China , Fermentação , Microbiologia de Alimentos , Lactobacillus/classificação , Lactobacillus/genética
12.
Clin Exp Pharmacol Physiol ; 48(5): 704-716, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33650189

RESUMO

Reduced nerve growth factor (NGF) is associated with cardiac sympathetic nerve denervation in heart failure (HF) which is characterized by increased oxidative stress. Apocynin is considered an antioxidant agent which inhibits NADPH oxidase activity and improves reactive oxygen species scavenging. However, it is unclear whether apocynin prevents reduced myocardial NGF, leading to improvement of cardiac function in HF. In this study, we tested the hypothesis that apocynin prevents reduced myocardial NGF, contributing to amelioration of myocardial apoptosis and failure. Rabbits with myocardial infarction (MI) or sham operation were randomly assigned to receive apocynin or placebo for 4 weeks. MI rabbits exhibited left ventricular (LV) dysfunction, and elevation in oxidative stress, as evidenced by a decreased reduced-to-oxidized glutathione ratio and an increased 4-hydroxynonenal expression, and reduction in NGF and NGF receptor tyrosine kinase A (TrKA) expression in the remote non-infarcted myocardium. Apocynin treatment ameliorated LV dysfunction, reduced oxidative stress, prevented decreases in NGF and TrKA expression and reduced cardiomyocyte apoptosis after MI. In cultured H9C2 cardiomyocytes, hypoxia or hydrogen peroxide decreased NGF expression, and apocynin normalized hypoxia-induced reduction of NGF. Recombinant NGF attenuated hypoxia-induced apoptosis. Apocynin prevented hypoxia-induced apoptosis, and the suppressive effect of apocynin on apoptosis was abolished by NGF receptor TrKA inhibitor K252a. We concluded that apocynin prevented reduced myocardial NGF, leading to attenuation of cardiomyocyte apoptosis and LV remodelling and dysfunction in HF after MI. These findings suggest that strategies to prevent NGF reduction by inhibition of oxidative stress may be of value in amelioration of LV dysfunction in HF.

13.
Food Res Int ; 140: 110037, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33648263

RESUMO

As a widely used Asian starter culture, the quality of daqu can significantly affect the organoleptic characteristics of the final products, yet the microbial metabolic network involved in flavor development remains unclear. This study aims to investigate that network based on the dynamics of physicochemical properties, microbial community, and volatile compounds in medium-temperature daqu (MT-daqu) during spontaneous fermentation. Analyses using the metagenomic data set facilitated the gene repertoire overview of this ecosystem, indicating that Lactobacillales (mainly Weissella, Lactobacillus, and Pediococcus), Mucorales (mainly Lichtheimia), and Eurotiales (mainly Aspergillus, Rasamsonia and Byssochlamys) were the potential predominant populations successively responsible for the production of lytic enzymes and flavor precursors/compounds in MT-daqu. Flavor-relevant pathways were found to exist in multiple species, but only bacteria showed the potential to participate in butane-2,3-diol (e.g. Weissella, Lactobacillus, and Staphylococcus) and butanoate (Thermoactinomyces) metabolism, and only fungi were potentially involved in biosynthesis of guaiacol (Byssochlamys) and 4-vinylguaiacol (Aspergillus). Furthermore, a combined analysis revealed that the acidic thermal environment present in early phases was mainly due to the catabolic activities of Lactobacillales and Lichtheimia, which could contribute to the effective self-domestication of microbiota. The study helps elucidate the different metabolic roles of microorganisms and disclose the formation mechanism of daqu's partial functions, namely providing various aromatic substances/precursors and enzymes.


Assuntos
Metagenômica , Microbiota , Bebidas Alcoólicas/análise , Redes e Vias Metabólicas , Microbiota/genética , Temperatura
14.
J Intensive Care Med ; : 885066621992320, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33626964

RESUMO

Septic shock with multiple organ failure is a devastating situation in clinical settings. Through the past decades, much progress has been made in the management of sepsis and its underlying pathogenesis, but a highly effective therapeutic has not been developed. Recently, macromolecules such as histones have been targeted in the treatment of sepsis. Histones primarily function as chromosomal organizers to pack DNA and regulate its transcription through epigenetic mechanisms. However, a growing body of research has shown that histone family members can also exert cellular toxicity once they relocate from the nucleus into the extracellular space. Heparin, a commonly used anti-coagulant, has been shown to possess life-saving capabilities for septic patients, but the potential interplay between heparin and extracellular histones has not been investigated. In this review, we summarize the pathogenic roles of extracellular histones and the therapeutic roles of heparin in the development and management of sepsis and septic shock.

15.
Anticancer Drugs ; 32(6): 647-656, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33587351

RESUMO

Triple-negative breast cancer (TNBC) is highly aggressive, with high rates of early relapse and very poor overall prognosis. Amphiregulin (AREG) is the most abundant epidermal growth factor receptor (EGFR) agonist in MDA-MB-231 TNBC cells, whose proliferation can be inhibited by (-)-epigallocatechin gallate (EGCG), a constituent of green tea that is prone to oxidative polymerization. The effect of dimeric-EGCG, a dimer of oxidized and polymerized EGCG, on MDA-MB-231 cell the proliferation warrants further exploration. In the present study, MTT, flow cytometry, migration scratch, transwell, western blotting, and surface plasmon resonance assays were used to evaluate the effect of dimeric-EGCG on MDA-MB-231 cells and explore the underlying mechanism. MDA-MB-231 cell proliferation and migration were significantly inhibited by dimeric-EGCG at concentrations as low as 10 µM. Levels of EGFR and p44/42 MAPK phosphorylation in MDA-MB-231 cells were significantly reduced by treatment with 10 µM dimeric-EGCG (P < 0.01). In addition, the levels of phosphorylation induced by exogenous AREG were also inhibited by dimeric-EGCG (P < 0.01); however, no significant effects of dimeric-EGCG were observed on epidermal growth factor or transforming growth factor-alpha signaling. Surface plasmon resonance analysis demonstrated that 10 µM dimeric-EGCG bound directly to the extracellular domain of EGFR, competitively inhibiting the binding of AREG to EGFR. These results suggest a novel mechanism underlying the inhibitory effect of dimeric-EGCG on MDA-MB-231 cells, with potential application in the development of drugs for the treatment of TNBC.

16.
Mol Biol Evol ; 38(5): 1995-2013, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33432361

RESUMO

Evolutionary fates of duplicated genes have been widely investigated in many polyploid plants and animals, but research is scarce in recurrent polyploids. In this study, we focused on foxl2, a central player in ovary, and elaborated the functional divergence in gibel carp (Carassius gibelio), a recurrent auto-allo-hexaploid fish. First, we identified three divergent foxl2 homeologs (Cgfoxl2a-B, Cgfoxl2b-A, and Cgfoxl2b-B), each of them possessing three highly conserved alleles and revealed their biased retention/loss. Then, their abundant sexual dimorphism and biased expression were uncovered in hypothalamic-pituitary-gonadal axis. Significantly, granulosa cells and three subpopulations of thecal cells were distinguished by cellular localization of CgFoxl2a and CgFoxl2b, and the functional roles and the involved process were traced in folliculogenesis. Finally, we successfully edited multiple foxl2 homeologs and/or alleles by using CRISPR/Cas9. Cgfoxl2a-B deficiency led to ovary development arrest or complete sex reversal, whereas complete disruption of Cgfoxl2b-A and Cgfoxl2b-B resulted in the depletion of germ cells. Taken together, the detailed cellular localization and functional differences indicate that Cgfoxl2a and Cgfoxl2b have subfunctionalized and cooperated to regulate folliculogenesis and gonad differentiation, and Cgfoxl2b has evolved a new function in oogenesis. Therefore, the current study provides a typical case of homeolog/allele diversification, retention/loss, biased expression, and sub-/neofunctionalization in the evolution of duplicated genes driven by polyploidy and subsequent diploidization from the recurrent polyploid fish.

17.
Sci China Life Sci ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33428077

RESUMO

Goldfish comprise around 300 different strains with drastically altered and aesthetical morphologies making them suitable models for evolutionary developmental biology. The dragon-eye strain is characterized by protruding eyes (analogous to those of Chinese dragons). Although the strain has been selected for about 400 years, the mechanism of its eye development remains unclear. In this study, a stable dragon-eye goldfish strain with a clear genetic background was rapidly established and studied. We found that upregulation of the PPAR signaling pathway accompanied by an increase in lipid accumulation might trigger the morphological and structural transformation of the eye in dragon-eye goldfish. At the developmental stage of proptosis (eye protrusion), downregulation of the phototransduction pathway was consistent with the structural defects and myopia of the dragon-eye strain. With the impairment of retinal development, cytokine-induced inflammation was activated, especially after proptosis, similar to the pathologic symptoms of many human ocular diseases. In addition, differentially expressed transcription factors were significantly enriched in the PAX and homeobox families, two well-known transcription factor families involved in eye development. Therefore, our findings reveal the dynamic changes in key pathways during eye development in dragon-eye goldfish, and provide insights into the molecular mechanisms underlying drastically altered eyes in goldfish and human ocular disease.

18.
BMC Genomics ; 22(1): 50, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446100

RESUMO

BACKGROUND: Loaches of Cobitinae, widely distributed in Eurasian continent, have high economic, ornamental and scientific value. However, the phylogeny of Cobitinae fishes within genera or family level remains complex and controversial. Up to now, about 60 Cobitinae mitogenomes had been deposited in GenBank, but their integrated characteristics were not elaborated. RESULTS: In this study, we sequenced and analyzed the complete mitogenomes of a female Cobits macrostigma. Then we conducted a comparative mitogenome analysis and revealed the conserved and unique characteristics of 58 Cobitinae mitogenomes, including C. macrostigma. Cobitinae mitogenomes display highly conserved tRNA secondary structure, overlaps and non-coding intergenic spacers. In addition, distinct base compositions were observed among different genus and significantly negative linear correlation between AT% and AT-skew were found among Cobitinae, genus Cobitis and Pangio mitogenomes, respectively. A specific 3 bp insertion (GCA) in the atp8-atp6 overlap was identified as a unique feature of loaches, compared to other Cypriniformes fish. Additionally, all protein coding genes underwent a strong purifying selection. Phylogenetic analysis strongly supported the paraphyly of Cobitis and polyphyly of Misgurnus. The strict molecular clock predicted that Cobitinae might have split into northern and southern lineages in the late Eocene (42.11 Ma), furthermore, mtDNA introgression might occur (14.40 Ma) between ancestral species of Cobitis and ancestral species of Misgurnus. CONCLUSIONS: The current study represents the first comparative mitogenomic and phylogenetic analyses within Cobitinae and provides new insights into the mitogenome features and evolution of fishes belonging to the cobitinae family.


Assuntos
Cipriniformes , Genoma Mitocondrial , Animais , Composição de Bases , Cipriniformes/genética , DNA Mitocondrial/genética , Evolução Molecular , Feminino , Filogenia , RNA de Transferência/genética
19.
Syst Appl Microbiol ; 44(1): 126171, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33360414

RESUMO

Two nitrogen-fixing and heavy oil degrading strains, designated RWY-5-1-1T and ROY-1-1-2, were isolated from an oil production mixture from Yumen Oilfield in China. The 16S rRNA gene sequence showed they belong to Azospirillum and have less than 96.1 % pairwise similarity with each species in this genus. The average nucleotide identity and digital DNA-DNA hybridization values between them and other type strains of Azospirillum species were less than 75.69 % and 22.0 %, respectively, both below the species delineation threshold. Pan-genomic analysis showed that the novel isolate RWY-5-1-1T shared 2145 core gene families with other type strains in Azospirillum, and the number of strain-specific gene families was 1623, almost two times more than the number known from other species. Furthermore, genes related to nitrogenase, hydrocarbon degradation and biosurfactant production were found in the isolates' genomes. Also, this strain was capable of reducing acetylene to ethylene at a rate of 22nmol ethylene h-1 (108 cells) and degrading heavy oil at a rate of 36.2 %. The major fatty acids and polar lipids were summed feature 8 (C18:1ω7c/C18:1ω6c), and phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylcholine. Furthermore, a combination of phenotypic, chemotaxonomic, phylogenetic and genotypic data clearly indicated that strains RWY-5-1-1T and ROY-1-1-2 represent a novel species, for which the name Azospirillum oleiclasticum sp. nov. is proposed. The type strain is RWY-5-1-1T (=CGMCC 1.13426T =KCTC 72259 T). Azospirillum novel strains with the ability of heavy oil degradation associated with the promotion of plant growth has never been reported to date.


Assuntos
Azospirillum/classificação , Fixação de Nitrogênio , Campos de Petróleo e Gás/microbiologia , Petróleo/metabolismo , Filogenia , Azospirillum/isolamento & purificação , Técnicas de Tipagem Bacteriana , China , DNA Bacteriano/genética , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Ubiquinona/análogos & derivados , Ubiquinona/química
20.
Rapid Commun Mass Spectrom ; 35(8): e9029, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33326132

RESUMO

RATIONALE: Ginger pulp is the dried rhizome scraped off the skin which originates from Zingiber officinale Rosc., a Zingiberaceae plant. Ginger peel is the dried rhizome skin of Zingiber officinale Rosc. (Zingiberaceae). The present work aims to investigate the different chemical constituents that are related to the medicinal properties of the ginger pulp and ginger peel. METHODS: A rapid ultra-high-performance liquid chromatography/electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC/ESI-QTOF/MS) method was developed for qualitative analysis of the constituents in different polarity extracted fractions of the pulp and peel of ginger rhizomes. RESULTS: A total of 83 compounds were identified from the pulp and peel of ginger rhizomes, including 36 diarylheptanoids, 25 gingerols and 22 other compounds. Nine of these were new compounds. In total, 46, 27, 65 and 51 compounds were identified from the crude extract, petroleum ether, ethyl acetate, and n-butanol fractions of the ginger pulp, respectively, and 60, 30, 70 and 62 compounds were identified from the crude extract, petroleum ether, ethyl acetate, n-butanol fractions of the ginger peel, respectively. Each identified compound is marked on the corresponding chromatogram. CONCLUSIONS: The integrated method is sensitive and reliable for searching the different chemical constituents from different polarity extracted fractions of the ginger pulp and ginger peel. This work may provide a significant contribution to research into the medicinal properties of the ginger pulp and ginger peel.

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