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1.
Environ Res ; 183: 109197, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32058142

RESUMO

There is a large body of evidence linking Environmental Tobacco Smoke (ETS) exposure with impaired lung function. However, it is not known whether exposure to pets modifies this relationship. To investigate if pet ownership changes the association between ETS exposure and lung function, a population-based sample of 7326 children, 7-14 years old, were randomly recruited from 24 districts in northeast China. Lung function including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), and maximal mid-expiratory flow (MMEF) was measured by spirometry, while pet ownership time periods and ETS exposure were collected by questionnaire. Two-level regression analysis was done, with covariates controlled for. The results showed pet exposure in certain early lifetime windows modified the associations of ETS exposure on decreased lung function in children. Among children exposed to current ETS, those exposed to pets in utero had greater reductions in lung function (for instance: OR for reduced FVC (<85% predicted) = 10.86; 95% CI: 3.80-30.97) than those not exposed to pets in utero (OR = 2.32; 95% CI: 1.76-3.05) (pinteraction = 0.005). While, children exposed to current pet ownership reduced the lung function impairment induced by ETS exposure during the first 2 years of life and/or ETS exposure during pregnancy, especially for FVC impairment. For instance, OR (95%CI) for reduced FVC (<85% predicted) was 0.81 (0.56, 1.18) and 1.42 (1.15, 1.74), respectively, for children with or without current pet ownership exposed to ETS during the first 2 years of life (pinteraction = 0.010). Furthermore, pet type or number of pets did not significantly modify associations between ETS exposure and lung function. In conclusion, the timing of pet ownership modified associations between ETS exposure and lung function, pet ownership in utero and during the first 2 years of life significantly worsened the adverse impacts of passive smoking on lung function.

2.
Chemosphere ; 248: 126000, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-32007774

RESUMO

Recently, the technology for the remediation of Cr(VI) pollutant via bisulfite has been found to be effective for fast elimination of co-contaminants especially in acidic solution, where free radicals (i.e., sulfate and/or hydroxyl radicals) are proposed to act as dominant oxidants. Here, it was demonstrated that high-valent Cr intermediate played a primary role in the Cr(VI)/bisulfite system through applying methyl phenyl sulfoxide (PMSO) as a probe. PMSO was effectively transformed in the Cr(VI)/bisulfite system with appreciable generation of methyl phenyl sulfone (PMSO2) product, while PMSO was oxidized by free radicals to hydroxylated and/or polymeric products rather than PMSO2. The involvement of high-valent Cr species was further supported by the formation of 18O-labeled PMSO2 in 18O labeling experiments, where the incorporation of 18O from solvent water H218O into PMSO2 was likely resulted from competitive oxygen exchange of Cr-oxo species with water. The relative contribution of high valent Cr species versus free radicals was evaluated based on the yield of PMSO2, which was dependent on the solution chemistry such as [Cr(VI)]:[bisulfite] ratio and dissolved oxygen. This work advances the understanding of chromium chemistry involved in the Cr(VI)/bisulfite system. These findings have important implications on the application of this "waste control by waste" technology for environmental decontamination.

3.
Sci Total Environ ; 715: 136859, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-32014767

RESUMO

BACKGROUND: Little is known about whether exposure to pets influences the association between hypertension and environmental tobacco smoke (ETS). The current study aims to examine the interaction of pet ownership on ETS exposure and the development of hypertension in children. METHODS: From 2012 to 2013, a total of 9354 children, 5 to 17 years of age, were recruited from 62 schools in seven northeastern cities. BP in children was measured and hypertension was defined as an average diastolic blood pressure (DBP) or systolic blood pressure (SBP) at or above the 95th percentile for that child's age, sex, and height. Pet ownership in three different time periods (in utero, past 2 years, and currently) and ETS exposure data were collected from parents via a questionnaire. Two-level regressions were used for the data analyses. RESULTS: The data show consistent, significant interactions between exposure to pets and effects from ETS. Children who were not exposed to pets experienced stronger effects from ETS on hypertension when compared to those exposed to pets, and the protective effect of pet ownership became stronger with a greater number of pets in the home. Exposure to in utero ETS was associated with hypertension [adjusted odds ratio (aOR) = 1.32, 95% confidence interval (CI): 1.13-1.54] only for those children without pet exposure in utero but not for those with pets (aOR = 0.75; 95% CI: 0.49-1.15) (pinteraction < 0.05). Moreover, household dog ownership was related to significantly lower effects of current ETS on hypertension (aOR = 0.80, 95% CI: 0.61-1.05) compared with children without dogs (aOR = 1.26, 95% CI: 1.11-1.44) (pinteraction = 0.001). Interaction associations between ETS and pet ownership were more robust for girls than for boys and for younger than older children. CONCLUSION: This study indicates an inverse relationship between pet ownership and ETS, potentially pointing to pet ownership as protecting against the development of hypertension in children.

4.
Biosci Biotechnol Biochem ; : 1-7, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32019421

RESUMO

Peptidic inhibitors of proteases are attracting increasing interest not only as drug candidates but also for studying the function and regulation mechanisms of these [Formula: see text] out a cyclic peptide inhibitor of human uPA (upain-1, CSWRGLENHRMC) and found that Ala substitution of P2 residue turns upain-1 to a substrate. To further investigate the effect of P2 residue on the peptide behavior transformation, we constructed upain-1-W3F, which has Phe replacement in the P2 position. We determined KD and Ki of upain-1-W3F and found that upain-1-W3F might still exist as an inhibitor. Furthermore, the high-resolution crystal structure of upain-1-W3F·uPA reveals that upain-1-W3F indeed stays as an intact inhibitor bind to uPA. We thus propose that the P2 residue plays a nonnegligible role in the conversion of upain-1 to a substrate. These results also proposed a strategy to optimize the pharmacological properties of peptide-based drug candidates by hydrophobicity and steric hindrance.Abbreviations : uPA: urokinase-type plasminogen activator; SPD: serine protease domain; S1 pocket: specific substrate-binding pocket.

5.
J Chem Inf Model ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32053358

RESUMO

Intrinsically disordered proteins (IDPs) exert their functions by binding to partner proteins via a complex process that includes coupled folding and binding. Motivated by that inhibiting the binding of the IDP p53 to its partner MDM2 has become a promising strategy for the design of anticancer drugs, we carried out metadynamics simulations to study the coupled folding and binding process linking the IDP p53 to MDM2 in atomic detail. Using bias-exchange metadynamics (BE-MetaD) and infrequent metadynamics (InMetaD) we estimated the binding free energy, the unbinding rate and the binding rate. By analyzing the stable intermediates, we uncovered the role of nonnative interactions played in the p53-MDM2 binding/unbinding process. We used a three-state model to describe the whole binding/unbinding process and to obtain the corresponding rate constants. Our work shows that the binding of p53 favors an induced fit mechanism which proceeds in a stepwise fashion. Our results can be helpful for the in-depth understanding of the coupled folding and binding process needed for the design of MDM2 inhibitors.

6.
Proc Natl Acad Sci U S A ; 117(6): 3144-3149, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32001509

RESUMO

Glycogen plays a central role in glucose homeostasis and is abundant in several types of tissue. We report an MRI method for imaging glycogen noninvasively with enhanced detection sensitivity and high specificity, using the magnetic coupling between glycogen and water protons through the nuclear Overhauser enhancement (NOE). We show in vitro that the glycogen NOE (glycoNOE) signal is correlated linearly with glycogen concentration, while pH and temperature have little effect on its intensity. For validation, we imaged glycoNOE signal changes in mouse liver, both before and after fasting and during glucagon infusion. The glycoNOE signal was reduced by 88 ± 16% (n = 5) after 24 h of fasting and by 76 ± 22% (n = 5) at 1 h after intraperitoneal (i.p.) injection of glucagon, which is known to rapidly deplete hepatic glycogen. The ability to noninvasively image glycogen should allow assessment of diseases in which glucose metabolism or storage is altered, for instance, diabetes, cardiac disease, muscular disorders, cancer, and glycogen storage diseases.

7.
BMC Oral Health ; 20(1): 43, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32028960

RESUMO

BACKGROUND: Better understanding of the danger zone anatomy in mesial roots (MRs) of mandibular first molars (MFMs) may serve to decrease the risk of mishaps. This study aimed to measure the minimal distal dentine thicknesses of danger zone in MRs of MFMs in a native Chinese population using cone-beam computed tomography (CBCT). METHODS: CBCT images of 1792 MFMs from 898 Chinese patients were analyzed. The minimal distal dentine thicknesses of the mesiobuccal (MB) and mesiolingual (ML) canals below the furcation 1, 2, 3, 4, 5 mm were measured. The association between the minimal distal dentine thicknesses and the root lengths, patient's age and gender, side were assessed. RESULTS: The minimal distal dentine thicknesses of MB and ML canals are located 3 ∼ 4 mm below the furcation for both men and women. There are no differences between MB and ML canals, while the minimal distal dentine thicknesses of MB and ML canals were higher in men than women (P < 0.05), except at 1 and 3 mm of ML canals (P > 0.05). The minimal distal dentine thicknesses of MB and ML canals increased with age in both men and women at each location (P < 0.05). The minimum distal dentine thickness at every location were significantly different between long teeth and short teeth both in men and women (P < 0.05), with short teeth having the smallest mean values. There are no significant differences between two sides (P > 0.05). CONCLUSIONS: The minimal distal dentine thicknesses of MRs in MSMs have close correlation with root length, patient's age and gender.

8.
Dev Comp Immunol ; : 103641, 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32045589

RESUMO

Perception of extracellular ATP (eATP), a common endogenous damage-associated molecular pattern, is through its receptor P2X7R. If eATP/P2X7R signaling is conserved throughout animal evolution is unknown. Moreover, little information is currently available regarding P2X7R in invertebrates. Here we demonstrated that the coral P2X7-like receptor, AdP2X7RL, the amphioxus P2X7-like receptor, BjP2X7RL and the flounder P2X7 receptor, PoP2X7R, shared common features characteristic of mammalian P2X7R, and their 3D structures displayed high resemblance to that of human P2X7R. Expression of Adp2x7rl, Bjp2x7rl and Pop2x7r was all subjected to the regulation by LPS and ATP. We also showed that AdP2X7RL, BjP2X7RL and PoP2X7R were distributed on the plasma membrane in AdP2X7RL-, BjP2X7RL- and PoP2X7R-expressing HEK cells, and had strong affinity to eATP. Importantly, the binding of AdP2X7RL, BjP2X7RL and PoP2X7R to eATP all induced similar downstream responses, including induction of cytokines (IL-1ß, IL-6, IL-8 and CCL-2), enhancement of phagocytosis and activation of AKT/ERK-associated signaling pathway observed for mammalian P2X7R. Collectively, our results indicate for the first time that both coral and amphioxus P2X7RL as well as flounder P2X7R can interact with eATP, and induce events that trigger mammalian mechanisms, suggesting the high conservation of eATP perception throughout multicellular animal evolution.

9.
Environ Monit Assess ; 192(2): 154, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32006115

RESUMO

The pollution levels of lakes vary in quantity and type of contaminants accumulated in their sediment and water. The second Chinese capital city will be built around Baiyangdian Lake in the near future, and thus, it is important to monitor pollution status of Baiyangdian Lake. This study mainly focused on the accumulated heavy metal concentrations in the surface sediment and in variety of fish bodies. Sediment pollution status and ecological risk were evaluated through geo-accumulation (I-geo), contamination factor (CF), pollution load index (PLI), potential ecological risk ([Formula: see text]), and mean probable effect concentration quotient (mPEC-Q). In addition, human health risks via fish consumption were also evaluated. Based on the results, the average sediment trace As, Cd, Cr, Cu, Mn, Ni, Pb, and Zn concentrations were 9.53, 0.35, 56.37, 32.33, 617.05, 30.18, 19.17, and 84.24 mg/kg dry wt, respectively. Both I-geo and [Formula: see text] inferred low pollution levels and low ecological risks from all assessed trace metals except Cd. Cd posed moderate to high ecological risks. Based on sediment quality guidelines (SQGs), average Ni and Cr concentrations exceeded the threshold effect concentrations (TEC), but their [Formula: see text] are low as their average concentrations is below Hebei province pre-contaminations (30.8 mg/kg for Ni and 68.3 mg/kg for Cr). There is no cumulative toxicity from all the metals through mPEC-Q. Omnivorous fish accumulated statistically insignificantly higher amounts of metals than carnivorous fish, except for Hg. The intake of 12.22 g/person/day fish muscle for the entire life is safe from noncarcinogenic human health problems.

10.
Acta Biomater ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32001369

RESUMO

The translocation of natural cell membranes to the surface of synthetic nanoparticles, which allows man-made vectors to share merits and functionalities created by nature, has been a hot subject of research in the past decade. The resulting biomimetic nanoparticles not only retain the physicochemical properties of nanomaterials, but also inherit the advantageous functions of source cells. Combined with the preponderances of both synthetic and natural platforms, the optimized biomimetic systems can maximize the drug delivery efficiency. In this review, we first summarize the preparation strategies of the biomimetic systems from the perspective of the correlation between the properties of nanoparticles and cell membranes. Six types of cell membrane-camouflaged nanoparticles are further introduced with an emphasis on their properties and performance. Finally, a concluding remark regarding the primary challenges and opportunities associated with these nanoparticles is presented. STATEMENT OF SIGNIFICANCE: Translocation of natural cell membranes to the surface of synthetic nanoparticles has been repeatedly highlighted in the past decade to endow man-made vectors with merits and functionalities created by nature; therefore, the resulting biomimetic systems not only retain the physicochemical properties of nanomaterials but also inherit the biological functions of source cells for efficient drug delivery. To provide a timely review on this hot and rapidly developing subject of research, this paper summarized recent progress on the cell membrane-camouflaged nanoparticles as drug carriers for cancer therapy, and focused primarily on six different types of cell membrane-coated nanoparticles with an emphasis on the preparation strategies from the perspective of the correlation between the properties of nanoparticles and cell membrane.

11.
Gen Physiol Biophys ; 39(1): 49-58, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32039824

RESUMO

As a naturally occurring flavone, luteolin has received much attention due to its antioxidant, anti-inflammatory and anticancer functions. In the present study, we investigated the effect of luteolin on colonic motility and its mechanism using isometric muscle recording and the whole-cell patch-clamp technique in mice. Luteolin dose-dependently inhibited colonic smooth muscles motility and CMMC significantly. BayK8644, an L-type Ca2+ channel agonist, significantly attenuated the luteolin-induced inhibition. Moreover, the calcium currents recorded in colonic smooth muscle cells were dramatically inhibited by luteolin. However, no significant changes were found in the luteolin-induced inhibitory effect in the presence of TEA, a nonselective K+ channel blocker, glibenclamide, an ATP-dependent K+ channel blocker, and apamin, a small-conductance Ca2+-activated K+ channel blocker. Additionally, luteolin did not affect potassium currents. Furthermore, TTX, a Na+ channel blocker, L-NAME, an inhibitor of nitric oxide (NO) synthase, ODQ, an inhibitor of NO-sensitive guanylyl cyclase, and Ani9, a specific ANO1 channels blocker, had no effect on the luteolin-induced suppression. These results suggest that luteolin inhibited colonic smooth muscle motility by inhibiting L-type calcium channels in mice but not through potassium channels, the enteric nervous system (ENS), NO signaling pathways or ANO1 channels of interstitial cells of Cajal (ICCs).

12.
Sci Total Environ ; 711: 135108, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32000343

RESUMO

Submerged macrophytes are widely distributed primary producer that play important roles in maintaining healthy aquatic ecosystems. Generally, the relationships between macrophytes and environmental factors are complicated, so nonlinear nonparametric models with relatively flexible structures are optimal for macrophyte habitat simulation. In this study, generalized additive model (GAM) was used to evaluate the response of the submerged macrophytes biomass to water environmental factors in the Baiyangdian Lake. Forward stepwise method was used to implement model optimization. Likelihood ratio test was used to determine whether adding a variable enhances the model performance. Four individual variables (water depth, transparency, total nitrogen, and total phosphorus) and two interaction terms (water depth × transparency and water depth × total phosphorus) were included in the optimal GAM. The optimal model explained 70.5% of the biomass variation with a relatively low residual deviance value (22.40). There was a significant correlation between the measured and predicted data (R2 = 0.716, p = 0.0004). The response lines generated by the model indicated that macrophyte biomass had a positive correlation with transparency but negative correlations with total nitrogen and nitrite nitrogen in water. The response patterns of macrophyte biomass to water depth and total phosphorus were unimodal. The biomass reached the maximum value when the water depth was about 2.1 m and the total phosphorus concentration was 0.07 mg/L. Water depth and transparency, which affect light availability, are critical physical variables affecting the conditions associated with the submerged macrophytes, and excess nitrite and phosphorus limiting macrophyte biomass.

13.
Langmuir ; 36(4): 837-843, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-31898908

RESUMO

Use of a plasma-polymerized (pp) layer under a polyurethane (PU) coating on aluminum dramatically improves the corrosion resistance. Compared to conventional polymer coatings, pp coatings are highly cross-linked, have better adhesion to substrates, and result in lower emission of volatile organic contents. Although past research has focused on the properties of comparatively thick pp films and on the use of pp films alone to protect metals, we consider here very thin pp coatings as a primer layer to improve corrosion resistance. Electrochemical impedance spectroscopy combined with salt spray lab tests show that the corrosion resistance of a PU coating on top of a pp coating from hexamethyldisiloxane (HMDSO) is much better than that of a PU coating directly on Al 3003. The relatively poor pull-off adhesion between PU and pp-HMDSO is readily addressed using a gradient coating by depositing a pp maleic anhydride layer over the pp-HMDSO coating or by modifying the surface composition of the pp-HMDSO coating with N2 plasma. X-ray photon spectroscopy analysis of the failure interface from pull-off tests makes clear that failure does not occur at the interface between the pp coating and the metal substrate. Field tests show the performance of the coating system with PU on a gradient coating on Al 3003 to be superior to that of a coating system of PU on chromate-treated Al 3003.

14.
Anal Chem ; 92(3): 2435-2442, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-31904935

RESUMO

The process and mechanism of silk degradation is still a bewildering mystery in the investigation and conservation of cultural relics, which rely on the development of accurate and tailored analysis technologies. Here, two advanced approaches, proteomics and immunology, were developed for determining the deterioration behavior of historic silk fabrics and artificially aged samples from the molecular to the holistic level. The surface morphology and secondary structure of silk were destroyed during degradation. Subsequently, the proteomics and immunology analysis demonstrated a new degradation model differing from previous reports. First, the amorphous region and the looser crystalline regions were destroyed together, and the macromolecular chains were broken randomly. Then, the tight ß-sheet blocks in the crystalline region were exposed and deteriorated, which expedited the degradation of tight ß-sheet blocks and relatively loose blocks in the crystalline domain as well as the amorphous domain, ultimately yielding small molecule polypeptides. However, the deterioration process of ancient fabrics could be accelerated by poor burial conditions, thus showing distinct destructive characteristics. Overall, the results gave us a more comprehensive and profound understanding of the degradation process of ancient silk.

15.
Cell Death Dis ; 11(1): 26, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932578

RESUMO

Mitochondrial dysfunction leads to loss of renal function and structure; however, the precise mechanisms by which mitochondrial function can regulate renal fibrosis remain unclear. Proximal tubular cells (PTCs) prefer fatty acid oxidation as their energy source and dysregulation of lipid metabolism has been linked to tubulointerstitial fibrosis (TIF). Here, we demonstrated that mitochondrial uncoupling protein 2 (UCP2) regulates TIF through the stimulation of lipid deposition and extracellular matrix (ECM) accumulation. We show that UCP2 expression was increased in human biopsy sample and mouse kidney tissues with TIF. Moreover, UCP2-deficient mice displayed mitigated renal fibrosis in I/R-induced mouse model of TIF. Consistent with these results, UCP2 deficiency displayed reduced lipid deposition and ECM accumulation in vivo and in vitro. In UCP2-deficient PTCs, inhibition of TIF resulted from downregulation of hypoxia-inducible factor-1α (HIF-1α), a key regulator of lipid metabolism and ECM accumulation. Furthermore, we describe a molecular mechanism by which UCP2 regulates HIF-1α stabilization through regulation of mitochondrial respiration and tissue hypoxia during TIF. HIF-1α inhibition by siRNA suppressed lipid and ECM accumulation by restoration of PPARα and CPT1α, as well as suppression of fibronectin and collagen I expression in PTCs. In conclusion, our results suggest that UCP2 regulates TIF by inducing the HIF-1α stabilization pathway in tubular cells. These results identify UCP2 as a potential therapeutic target in treating chronic renal fibrosis.

16.
Carbohydr Polym ; 230: 115640, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887895

RESUMO

Bone transplantations are still facing many serious challenges, hydrogel as a new kind of artificial bone substitutes has developed into a promising bone scaffold material. However, it is still a challenge to combine bioactive agents and hydrogel matrix to promote osteoinductivity. Herein, we developed a novel bioactive hydrogel based on arginine-based unsaturated poly (ester amide) (Arg-UPEA) and methacrylated hyaluronic acid (HA-MA) via photo-crosslinking. As the results indicated, we found that the introduction of Arg-UPEA into HA-MA hydrogels could finely modulate their compressive modulus, swelling level and porous structure. Besides, among groups of different feed ratio, groups of 10 % and 15 % of Arg-UPEA content effectively enhanced osteogenic differentiation in osteoblasts when compared with HA-MA hydrogel. Furthermore, better bone regeneration and expression of osteogenesis-related factors in vivo also verified the Arg-UPEA/HA-MA hybrid hydrogels as a promising scaffold material for bone tissue engineering.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31907810

RESUMO

Eco-efficiency plays a significant role in expressing how efficient the economic activity consumes nature's goods and services. To accurately measure eco-efficiency, the method slack-based measure modified three-stage data envelopment analysis (DEA) is adopted to evaluate environmental conditions in China's 30 provinces from year 2004 to 2016. This study treats carbon emissions and three industrials wastes as undesirable outputs and excludes the influences from external environment and random errors when make adjustments. Based on the results, this study makes the following conclusions: Firstly, industrial structure, trade openness, and population have negative effects on eco-efficiency while technology investment, urbanization process, foreign direct investment, and fiscal decentralization have positive effects on eco-efficiency. Secondly, the eco-efficiency for most provinces after adjusted is lower than the pre-adjusted, which indicates the overestimation in eco-efficiency when using traditional approaches. Thirdly, the eco-efficiency in China showed a clear geographical step distribution, with the highest eco-efficiency in the east area, followed by the central, northwest, and southwest regions.

18.
Dev Comp Immunol ; 106: 103613, 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31935401

RESUMO

Teleost fish are the most primitive bony vertebrates that contain B cells; thus, comparative analysis of teleost naïve/mature B cells and plasma cells can provide helpful evidence for understanding the evolution paradigms of these two B-cell subpopulations in vertebrates. In this study, we developed monoclonal antibody against grass carp IgM and identified two different IgM+ cell subsets: IgM+ lymphocytes (Lym), resembling naïve/mature B cells, and IgM+ myeloid cells (Mye), resembling plasma cells. Like plasma cells in mammals, the size of IgM+ Mye is significantly larger than that of IgM+ Lym, as revealed by flow cytometric analysis and transmission electron microscopy. The IgM+ Mye were further verified as plasma cells because they showed gene expression patterns similar with those of human plasma cells and a great capacity to secrete IgM. Like mammalian IgM+ and IgA+ plasma cells, not IgG+ plasma cells, grass carp IgM+ Mye also expressed membrane immunoglobulins, a feature conserved in IgM+ plasma cells in vertebrates. Furthermore, recombinant CD40L or IL-21 alone could induce the plasma cell generation and IgM secretion, while the combination of CD40L and IL-21 had greater effect on IgM secretion, but not on plasma cell generation. This study fills an important gap in the knowledge of plasma cells in teleost fish and provides critical insights into the conserved evolution of IgM+ plasma cells in vertebrates.

19.
Cancer Lett ; 474: 94-105, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31954771

RESUMO

Nuclear factor erythroid-2-related factor 2 (Nrf2), a transcription factor, participates in protecting cells from electrophilic or oxidative stresses through regulating expression of cytoprotective and antioxidant genes. It has become one of the emerging targets for cancer chemosensitization, and small molecule inhibitors of Nrf2 can enhance the efficacy of chemotherapeutic drugs. Here, we found that flumethasone, a glucocorticoid, inhibited Nrf2 signaling in A549 and H460 cells by promoting Nrf2 protein degradation. Moreover, flumethasone significantly increased the sensitivity of A549 and H460 cells to chemotherapeutic drugs including cisplatin, doxorubicin and 5-FU. In mice bearing A549-shControl cells-derived xenografts, the size and weight of xenografts in the flumethasone and cisplatin combination group had a significant reduction compared with those in the cisplatin group, while in mice bearing A549-shNrf2 cells-derived xenografts, the size and weight of the xenografts in the combination group had no significant difference compared with those in the cisplatin group, demonstrating that chemosensitization effect of flumethasone is Nrf2-dependent. This work suggests that flumethasone can potentially be used as an adjuvant sensitizer to enhance the efficacy of chemotherapeutic drugs in lung cancer.

20.
Int J Biol Macromol ; 148: 333-341, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31954783

RESUMO

Deacetyl-7-aminocephalosporanic acid (D-7-ACA) is required for producing of many semisynthetic ß-lactam antibiotics; therefore, enzymes capable of converting 7-aminocephalosporanic acid (7-ACA) to D-7-ACA present a valuable resource to the pharmaceutical industry. In the present study, a putative acetylesterase, EstZY, was identified and characterized from a thermophilic bacterium Alicyclobacillus tengchongensis. Sequence alignment showed that EstZY was an acetylesterase which belonged to carbohydrate esterase family 7 (CE7), with substrate preference for short-chain acyl esters p-NPC2 to p-NPC8. Maximum enzyme activity was recorded at pH 9.0 and 50 °C, where Km and Vmax were calculated as 1.9 ± 0.23 mM and 258 ± 18.5 µM min-1, respectively. The residues Ser185, Asp274, and His303 were identified as the putative catalytic triad by homology modelling, site-directed mutagenesis and molecular docking. Moreover, EstZY can remove the acetyl group at C3' position of 7-ACA to form D-7-ACA; this is the first report of a 7-ACA deacetylase from CE7 family in A. tengchongensis and may represent a new enzyme with industrial values.

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