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1.
Sci Data ; 11(1): 1028, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39300149

RESUMEN

The functional traits of soil protists have been employed in ecological research to enhance comprehension of the underlying mechanisms of ecological processes. Among the numerous soil protists, testate amoebae emerge as a prominent and abundant group, playing a pivotal role in soil micro-food webs. Furthermore, they are regarded as valuable bioindicators for environmental monitoring and palaeoecological studies due to their sensitivity to environmental changes. We screened 372 testate amoebae species widely distributed across Northern Holarctic realm and collected trait data, representing the morphological and feeding characteristics of testate amoebae. The dataset would provide valuable basis for investigation of the functional diversity and ecological roles of testate amoebae, thus facilitating further research on soil protist communities and ecosystem dynamics.


Asunto(s)
Amoeba , Suelo , Ecosistema , Cadena Alimentaria
2.
Oecologia ; 205(3-4): 691-707, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39115695

RESUMEN

The relationship between species diversity and spatial scale is a central topic in spatial community ecology. Latitudinal gradient is among the core mechanisms driving biodiversity distribution on most scales. Patterns of ß-diversity along latitudinal gradient have been well studied for aboveground terrestrial and marine communities, whereas soil organisms remain poorly investigated in this regard. The West Siberian Plain is a good model to address diversity scale-dependence since the latitudinal gradient does not overlap with other possible factors such as elevational or maritime. Here, we collected 111 samples following hierarchical sampling (sub-zones, ecosystem types, microhabitat and replicate samples) and performed multi-scale partitioning of ß-diversity of testate amoeba assemblages as a model of study. We found that among-ecosystem ß-diversity is a leading scale in testate amoeba assemblages variation. Rare species determine ß-diversity at all scale levels especially in the northern regions, where rare taxa almost exclusively accounted for the diversity at the ecosystem level. ß-Diversity is generally dominated by the turnover component at all scales in lower latitudes, whereas nestedness prevailed at among-ecosystem scale in higher latitudes. These findings indicate that microbial assemblages in northern latitudes are spatially homogeneous and constrained by historical drivers at larger scales, whereas in southern regions, it is dominated by the turnover component both at the microhabitat and ecosystem scales and therefore determined by recent vegetation and environmental heterogeneity. Overall, we have provided the evidence for the existence of negative latitudinal gradient for among-ecosystem ß-diversity but not for among-microhabitat and among-sample ß-diversity for terrestrial testate amoeba communities.


Asunto(s)
Amoeba , Biodiversidad , Ecosistema
3.
Langmuir ; 40(33): 17526-17535, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39102742

RESUMEN

The adsorption behaviors and electronic properties of five gas molecules (CO, H2O, NH3, NO, and C2H6O) on the intrinsic Ti2CO2 and Fe-doped Ti2CO2 were calculated and studied based on first principles. The adsorption height, bond length change, adsorption energy, charge transfer, band structure, differential charge, work function, and recovery time of the two gas adsorption systems were discussed, and their sensing performance was evaluated. The results show that the CO gas molecules have the best adsorption energy and charge transfer on Ti2CO2 modified by the Fe atom (Ti2CO2-Fe). The electrical conductivity obviously increases with the decrease of the band gap, which changes from semiconductor to conductor behavior. The reduction of the work function in the Ti2CO2-Fe system weakens the binding of the electron, which improves the electron flow between the substrate and the gas molecules. In addition, the Ti2CO2-Fe system with H2O molecule participation remained the best adsorption effect on CO gas, and the fast recovery time was 625 s at 398 K. Therefore, Ti2CO2-Fe is a prospective material for the advancement of CO gas-sensitive sensors.

4.
Sci Total Environ ; 947: 174717, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-38997027

RESUMEN

Retinoic acid receptors (RARs) are known as crucial endocrine receptors that could mediate a broad diversity of biological processes. However, the data on endocrine disrupting effects of emerging chemicals by targeting RAR (ant)agonism are far from sufficient. Herein, we investigated the RARα agonistic or antagonistic activities for 75 emerging chemicals of concern, and explored their interactions with this receptor. A recombinant two-hybrid yeast assay was used to examine the RARα activities of the test chemicals, wherein 7 showed effects of RARα agonism and 54 exerted potentials of RARα antagonism. The representative chemicals with RARα agonistic activities, i.e. 4-hydroxylphenol (4-HP) and bisphenol AF (BPAF), significantly increased the mRNA levels of CRABP2 and CYP26A1, while 4 select chemicals with RARα antagonistic potentials, including bisphenol A (BPA), tetrabromobisphenol A (TBBPA), 4-tert-octylphenol (4-t-OP), and 4-n-nonylphenol (4-n-NP), conversely decreased the transcriptional levels of the test genes. The in silico molecular docking analysis using 3 different approaches further confirmed the substantial binding between the chemicals with RARα activities and this nuclear receptor protein. This work highlights the promising strategy for screening endocrine-disrupting effects of emerging chemicals of concern by targeting RARα (ant)agonism.


Asunto(s)
Disruptores Endocrinos , Receptor alfa de Ácido Retinoico , Xenobióticos , Receptor alfa de Ácido Retinoico/metabolismo , Receptor alfa de Ácido Retinoico/genética , Humanos , Simulación del Acoplamiento Molecular , Simulación por Computador , Receptores de Ácido Retinoico/metabolismo
5.
Heliyon ; 10(13): e33638, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39071716

RESUMEN

Background: Gestational diabetes mellitus (GDM) is a common condition observed globally, and previous studies have suggested a link between GDM and insomnia. The objective of this study was to elucidate the causative relationship between insomnia and GDM, and to investigate the influence of factors related to insomnia on GDM. Methods: We performed bidirectional Mendelian randomization (MR) analyses using single nucleotide polymorphisms (SNPs) as genetic instruments for exposure and mediators, thereby minimizing bias due to confounding and reverse causation. The Cochran Q test was utilized for heterogeneity analysis, MR-Egger regression for pleiotropy assessment, and the leave-one-out method for evaluating the robustness of the results. Additionally, we determined the causal relationships between GDM and other factors such as coffee consumption, alcohol intake, and household income. Results: Insomnia was positively associated with GDM, as indicated by 39 SNPs (OR = 1.27, 95 % CI 1.12-1.439, P-value = 0.008). Conversely, the MR analysis did not reveal any causal relationship between GDM and insomnia (OR = 1.032, 95 % CI 0.994-1.071, P-value = 0.99). Additionally, no causal relationship was observed between coffee consumption, alcohol intake, household income, and GDM (all P-values >0.05). Conclusion: Our study indicates that insomnia elevates the risk of GDM, thereby establishing a causal link with GDM, independent of coffee consumption, alcohol intake, and household income.

6.
Research (Wash D C) ; 7: 0317, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38357698

RESUMEN

Silica glass, known for its brittleness, weight, and non-biodegradable nature, faces challenges in finding suitable alternatives. Transparent wood, made by infusing polymers into wood, shows promise but is hindered by limited availability of wood in China and fire risks associated with its use. This study explores the potential of utilizing bamboo, which has a shorter growth cycle, as a valuable resource for developing flame-retardant, smoke-suppressing, and superhydrophobic transparent bamboo. A 3-layered flame-retardant barrier, composed of a top silane layer, an intermediate layer of SiO2 formed through hydrolysis-condensation of Na2SiO3 on the surface, and an inner layer of Na2SiO3, has been confirmed to be effective in reducing heat release, slowing flame spread, and inhibiting the release of combustible volatiles, toxic smoke, and CO. Compared to natural bamboo and other congeneric transparent products, the transparent bamboo displays remarkable superiority, with the majority of parameters being notably lower by an entire order of magnitude. It achieves a long ignition time of 116 s, low total heat release (0.7 MJ/m2), low total smoke production (0.063 m2), and low peak CO concentration (0.008 kg/kg). Moreover, when used as a substrate for perovskite solar cells, the transparent bamboo displays the potential to act as a light management layer, leading to a marked efficiency enhancement of 15.29%. The excellent features of transparent bamboo make it an enticing choice for future advancements in flame-retardant glasses and optical devices.

7.
Br J Pharmacol ; 181(5): 640-658, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-37702564

RESUMEN

BACKGROUND AND PURPOSE: Atherosclerosis induced by cyclosporine A (CsA), an inhibitor of the calcineurin/nuclear factor of activated T cells (NFAT) pathway, is a major concern after organ transplantation. However, the atherosclerotic mechanisms of CsA remain obscure. We previously demonstrated that calcineurin/NFAT signalling inhibition contributes to atherogenesis via suppressing microRNA-204 (miR-204) transcription. We therefore hypothesised that miR-204 is involved in the development of CsA-induced atherosclerosis. EXPERIMENTAL APPROACH: ApoE-/- mice with macrophage-miR-204 overexpression were generated to determine the effects of miR-204 on CsA-induced atherosclerosis. Luciferase reporter assays and chromatin immunoprecipitation sequencing were performed to explore the targets mediating miR-204 effects. KEY RESULTS: CsA alone did not significantly affect atherosclerotic lesions or serum lipid levels. However, it exacerbated high-fat diet-induced atherosclerosis and hyperlipidemia in C57BL/6J and ApoE-/- mice, respectively. miR-204 levels decreased in circulating monocytes and plaque lesions during CsA-induced atherosclerosis. The upregulation of miR-204 in macrophages inhibited CsA-induced atherosclerotic plaque formation but did not affect serum lipid levels. miR-204 limited the CsA-induced foam cell formation by reducing the expression of the scavenger receptors SR-BII and CD36. SR-BII was post-transcriptionally regulated by mature miR-204-5p via 3'-UTR targeting. Additionally, nuclear-localised miR-204-3p prevented the CsA-induced binding of Ago2 to the CD36 promoter, suppressing CD36 transcription. SR-BII or CD36 expression restoration dampened the beneficial effects of miR-204 on CsA-induced atherosclerosis. CONCLUSION AND IMPLICATIONS: Macrophage miR-204 ameliorates CsA-induced atherosclerosis, suggesting that miR-204 may be a potential target for the prevention and treatment of CsA-related atherosclerotic side effects.


Asunto(s)
Aterosclerosis , MicroARNs , Placa Aterosclerótica , Animales , Ratones , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Aterosclerosis/inducido químicamente , Aterosclerosis/genética , Calcineurina/metabolismo , Antígenos CD36/metabolismo , Ciclosporina/efectos adversos , Ciclosporina/metabolismo , Lípidos , Macrófagos , Ratones Endogámicos C57BL , MicroARNs/genética , MicroARNs/metabolismo , Placa Aterosclerótica/inducido químicamente , Placa Aterosclerótica/metabolismo
8.
Sci Total Environ ; 882: 163593, 2023 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-37087015

RESUMEN

Parabens, as the synthetic preservatives, have caused universal environmental contamination and human exposure. Whether parabens could disturb neuroendocrine system was still ambiguous. In this study, the effects of four commonly-used parabens, i.e. methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP) and butyl paraben (BuP), were tested on the neuroendocrine system of zebrafish larvae by investigating the swimming behavior, the related hormones and biomarkers in the hypothalamic-pituitary-interrenal (HPI) axis. The results showed that all test chemicals significantly reduced the swimming distance and mean velocity of zebrafish larvae. The adrenocorticotropic hormone (ACTH) levels in zebrafish larvae were significantly increased, while the cortisol levels were obviously decreased by paraben exposure. The transcriptional analysis showed that the expressions of the target genes including gr, mr and crhr2 in the HPI axis were mostly down-regulated. The exploration of the initial molecular event showed that parabens could bind with the glucocorticoid receptor (GR) and trigger its transactivation, according to MDA-kb2 luciferase assay and molecular docking analysis. The interaction of parabens with the GR included the hydrogen bond and hydrophobic interaction. The findings herein revealed the potential deleterious effects of parabens on the neuroendocrine system of zebrafish larvae, thus accumulating the in vivo toxicological data on this kind of food preservatives.


Asunto(s)
Contaminantes Ambientales , Parabenos , Humanos , Animales , Parabenos/análisis , Pez Cebra/metabolismo , Contaminantes Ambientales/análisis , Simulación del Acoplamiento Molecular , Exposición a Riesgos Ambientales/análisis , Sistemas Neurosecretores
9.
Org Lett ; 25(11): 1974-1977, 2023 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-36920185

RESUMEN

An efficient rhodium-catalyzed dearomative rearrangement of 2-oxypyridines with quinone diazides has been developed for the direct synthesis of N-arylated pyridones, in which a novel 1,6-O-to-O rather than 1,4-O-to-C acyl rearrangement has been achieved under mild reaction conditions.

10.
iScience ; 26(2): 105964, 2023 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-36818307

RESUMEN

Traditional electrode materials still face vital challenges of few active sites, low porosity, complex synthesis process, and low specific capacitance. Herein, N-doped and 3D hierarchical porous graphene nanofoam (N-GNF) is created on carbon fibers (CFs) by employing a facile, fast, and environmentally friendly strategy of N2 plasma activation. After an appropriated N2 plasma activation, the graphene nanosheets (GNSs) synthesized by Ar/CH4 plasma deposition transform into N-GNF successfully. N doping donates rich active sites and increases the hydrophilia, while hierarchical nanoarchitecture exposes an enlarged effective contact area at the interface between electrode and electrolyte and affords sufficient space for accommodating more electrolytes. The as-assembled flexible N-GNF@CFs//Zn NSs@CFs Zn ion capacitor delivered a high energy density of 105.2 Wh kg-1 at 378.6 W kg-1 and initial capacity retention of 87.9% at the current of 2 A g-1 after a long cycle of 10,000.

11.
Front Pharmacol ; 13: 1040999, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36457708

RESUMEN

Obesity-induced metabolic syndrome is a rapidly growing conundrum, reaching epidemic proportions globally. Chronic inflammation in obese adipose tissue plays a key role in metabolic syndrome with a series of local and systemic effects such as inflammatory cell infiltration and inflammatory cytokine secretion. Adipose tissue macrophages (ATM), as one of the main regulators in this process, are particularly crucial for pharmacological studies on obesity-related metabolic syndrome. Ponatinib, a multi-targeted tyrosine kinase inhibitor originally used to treat leukemia, has recently been found to improve dyslipidemia and atherosclerosis, suggesting that it may have profound effect on metabolic syndrome, although the mechanisms underlying have not yet been revealed. Here we discovered that ponatinib significantly improved insulin sensitivity in leptin deficient obese mice. In addition to that, ponatinib treatment remarkably ameliorated high fat diet-induced hyperlipidemia and inhibited ectopic lipid deposition in the liver. Interestingly, although ponatinib did not reduce but increase the weight of white adipose tissue (WAT), it remarkably suppressed the inflammatory response in WAT and preserved its function. Mechanistically, we showed that ponatinib had no direct effect on hepatocyte or adipocyte but attenuated free fatty acid (FFA) induced macrophage transformation from pro-inflammatory to anti-inflammatory phenotype. Moreover, adipocytes co-cultured with FFA-treated macrophages exhibited insulin resistance, while pre-treat these macrophages with ponatinib can ameliorate this process. These results suggested that the beneficial effects of ponatinib on metabolic disorders are achieved by inhibiting the inflammatory phenotypic transformation of ATMs, thereby maintaining the physiological function of adipose tissue under excessive obesity. The data here not only revealed the novel therapeutic function of ponatinib, but also provided a theoretical basis for the application of multi-target tyrosine kinase inhibitors in metabolic diseases.

12.
J Org Chem ; 87(24): 16937-16940, 2022 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-36455299

RESUMEN

We present here a rhodium-catalyzed reaction between N-acyl pyridazinones and diazoacetates, leading to pyridazine derivatives in good yield under mild reaction conditions. This whole sequence probably proceeds through a carbene insertion into a C═O bond and an unprecedented 1,4-N-to-O acyl rearrangement reaction.

13.
Carbohydr Polym ; 296: 119905, 2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36088018

RESUMEN

A nature-inspired strategy is developed to build dual-network hydrogels made up of rigid graphene oxide-functionalized nanocellulose (GO@NC) network and flexible poly[acrylamide-co-(acrylic acid)] (poly(AAm-co-AAc)) network. A pre-stretching method is used to form a muscle-shape anisotropic architecture. The penetration of poly(AAm-co-AAc) flexible network relieves the stiffness of NC network, thus improving the average elongation at break from 86.2 % to 748.0 %. Compared with the poly(AAm-co-AAc), the average rupture tensile strength rises remarkably by 228.6 %. The dual-crosslinked strategy endows the GO@NC-poly(AAm-co-AAc) hydrogels with a fast, stable and repeatable self-healing ability, which can achieve 85.0 % of healing efficiency after only 600 s of self-healing and maintain 76.2 % of initial strength after 10 cycles of breaking-self-healing. The superb self-healing ability is similar to the muscle function. For potential applications, the hydrogels can achieve real-time, stable, and long-term sensing as smart wearable strain sensors (high gauge factor: 5.13), and can effectively purify Sudan IV wastewater as green recyclable adsorbents.


Asunto(s)
Grafito , Hidrogeles , Acrilamidas , Poli A , Resistencia a la Tracción
14.
Front Immunol ; 13: 943783, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36119040

RESUMEN

Basic research for prevention and treatment of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues worldwide. In particular, multiple newly reported cases of autoimmune-related diseases after COVID-19 require further research on coronavirus-related immune injury. However, owing to the strong infectivity of SARS-CoV-2 and the high mortality rate, it is difficult to perform relevant research in humans. Here, we reviewed animal models, specifically mice with coronavirus-related immune disorders and immune damage, considering aspects of coronavirus replacement, viral modification, spike protein, and gene fragments. The evaluation of mouse models of coronavirus-related immune injury may help establish a standardised animal model that could be employed in various areas of research, such as disease occurrence and development processes, vaccine effectiveness assessment, and treatments for coronavirus-related immune disorders. COVID-19 is a complex disease and animal models cannot comprehensively summarise the disease process. The application of genetic technology may change this status.


Asunto(s)
COVID-19 , Glicoproteína de la Espiga del Coronavirus , Animales , Modelos Animales de Enfermedad , Humanos , Ratones , SARS-CoV-2
15.
Front Aging Neurosci ; 14: 773687, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35721029

RESUMEN

Objective: To explore the effect of moxa cone moxibustion on N-acetyl aspartate/total creatinine (NAA/tCr) and choline/total creatinine (Cho/tCr) in the bilateral hippocampus (HIP) and bilateral posterior cingulate gyrus (PCG) in patients with mild cognitive impairment (MCI) using hydrogen proton magnetic resonance spectroscopy (1H-MRS) and to provide imaging basis for moxa cone moxibustion treatment for MCI. Methods: One hundred eight patients with MCI were served as the MCI group, and 67 age-matched subjects were enrolled as the normal control group. The MCI group was randomized and allocated into acupoint group, drug group, and sham acupoint group, with 36 cases in each group. Some patients in each group withdrew. Finally, 25 cases were included in the acupoint group, 24 cases in the drug group, and 20 cases in the sham acupoint group. The drug group was treated with oral donepezil hydrochloride. The acupoint group and sham acupoint group received moxa cone moxibustion treatment. Mini-mental state exam (MMSE) and Montreal cognitive assessment (MoCA) scores were recorded before intervention, at the end of the first and the second months of intervention, and in the 5th month of follow-up. The NAA/tCr and Cho/tCr ratios in the HIP and PCG were bilaterally measured by 1H-MRS before and after intervention. Results: Before intervention, compared with the normal control group, the MMSE and MoCA scores, the Cho/tCr ratio in the right HIP, the NAA/tCr ratio in the bilateral HIP, and the NAA/tCr ratio in the left PCG in the three treatment groups decreased significantly (both p < 0.01), and the NAA/tCr ratio in the right PCG significantly reduced in the acupoint and drug groups (p < 0.05). After two months of treatment, compared with the normal control group, there were no differences in the MoCA scores, the NAA/tCr, and Cho/tCr ratios in the bilateral PCG and bilateral HIP in the three treatment groups (p > 0.05). However, the MMSE scores in the drug group decreased when compared with the acupoint group and normal control group (p < 0.05, p < 0.01). The scores of MMSE and MoCA in the acupoint group and sham acupoint group at all time points were better than those in the drug group, which were similar to those in the normal control group. Conclusion: Our findings suggest that moxibustion could improve the cognitive function of patients with MCI. The mechanism may be related to the improvement of abnormal brain metabolism in HIP and PCG.

16.
J Hazard Mater ; 435: 129024, 2022 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-35523094

RESUMEN

The screening of compounds with endocrine disrupting effects has been attracting increasing attention due to the continuous release of emerging chemicals into the environment. Testing the (ant)agonistic activities of these chemicals on the retinoic acid receptor α (RARα), a vital nuclear receptor, is necessary to explain their perturbation in the endocrine system in vivo. In the present study, MCF-7 breast carcinoma cells were transiently transfected with a RARα expression vector (pEF1α-RARα-RFP) and a reporter vector containing a retinoic acid reaction element (pRARE-TA-Luc). Under optimized conditions, the performance of the newly constructed system was evaluated for its feasibility in screening the (ant)agonistic effects of emerging phenolic compounds on RARα. The results showed that this transient transfection cell model responded well to stimulation with (ant)agonists of RARα, and the EC50 and IC50 values were 0.87 nM and 2.67 µM for AM580 and Ro41-5253, respectively. Its application in testing several emerging phenolic compounds revealed that triclosan (TCS) and tetrabromobisphenol A (TBBPA) exerted notable RARα antagonistic activities. This newly developed bioassay based on MCF-7 is promising in identifying the agonistic or antagonistic activities of xenobiotics on RARα and has good potential for studying RARα signaling-involved toxicological effects of emerging chemicals of concern.


Asunto(s)
Hormigas , Neoplasias de la Mama , Animales , Bioensayo , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Detección Precoz del Cáncer , Femenino , Humanos , Células MCF-7 , Fenoles/toxicidad , Receptores de Ácido Retinoico/química , Receptores de Ácido Retinoico/genética , Receptores de Ácido Retinoico/metabolismo , Transfección
17.
Front Physiol ; 13: 784521, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35222071

RESUMEN

Phosphate (Pi) is one of the basic necessities required for sustenance of life and its metabolism largely relies on excretory function of the kidney, a process chiefly under the endocrine control of bone-derived fibroblast growth factor 23 (FGF23). However, knowledge gap exists in understanding the regulatory loop responsible for eliciting phophaturic response to Pi treatment. Here, we reported a novel role of (pro)renin receptor (PRR) in mediating phosphaturic response to Pi treatment via upregulation of FGF23 production. Male Sprague-Dawley rats were pretreated for 5 days via osmotic pump-driven infusion of a PRR antagonist PRO20 or vehicle, and then treated with high Pi (HP) solution as drinking fluid for the last 24 h. PRO20 reduced HP-induced Pi excretion by 42%, accompanied by blunted upregulation of circulating FGF23 and parathyroid hormone (PTH) and downregulation of renal Na/Pi-IIa expression. In cultured osteoblast cells, exposure to HP induced a 1.56-fold increase in FGF23 expression, which was blunted by PRO20 or siRNA against PRR. Together, these results suggest that activation of PRR promotes phosphaturic response through stimulation of FGF23 production and subsequent downregulation of renal Na/Pi-IIa expression.

18.
Org Lett ; 24(8): 1637-1641, 2022 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-35191701

RESUMEN

An enantioselective cyclopropanation reaction of N-substituted 2-pyridones with diazo compounds has been realized by using a chiral rhodium complex as the catalyst, and the corresponding chiral cyclopropanes could be formed in good yields with high enantioselectivities. Moreover, using acceptor-acceptor dimethyl 2-diazomalonate as the carbene precursor, a novel 1,4-rearrangement of a Boc group from N to C has also been discovered under rhodium catalysis.

19.
Am J Physiol Renal Physiol ; 322(4): F437-F448, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-35073210

RESUMEN

Calcineurin inhibitors such as cyclosporin A (CsA) have been widely used to improve graft survival following solid-organ transplantation. However, the clinical use of CsA is often limited by its nephrotoxicity. The present study tested the hypothesis that activation of the (pro)renin receptor (PRR) contributes to CsA-induced nephropathy by activating the renin-angiotensin system (RAS). Renal injury in male Sprague-Dawley rats was induced by a low-salt diet combined with CsA as evidenced by elevated plasma creatinine and blood urea nitrogen levels, decreased creatinine clearance and induced renal inflammation, apoptosis and interstitial fibrosis, and elevated urinary N-acetyl-ß-d-glucosaminidase activity and urinary kidney injury molecule-1 content. Each index of renal injury was attenuated following 2 wk of treatment with the PRR decoy inhibitor PRO20. Although CsA-treated rats with kidney injury displayed increased renal soluble (s)PRR abundance, plasma sPRR, renin activity, angiotensin II, and heightened urinary total prorenin/renin content, RAS activation was attenuated by PRO20. Exposure of cultured human renal proximal tubular HK-2 cells to CsA induced expression of fibronectin and sPRR production, but the fibrotic response was attenuated by PRO20 and siRNA-mediated PRR knockdown. These findings support the hypothesis that activation of PRR contributes to CsA-induced nephropathy by activating the RAS in rats. Of importance, we provide strong proof of concept that targeting PRR offers a novel therapeutic strategy to limit nephrotoxic effects of immunosuppressant drugs.NEW & NOTEWORTHY The present study reports, for the first time, that activation of the (pro)renin receptor drives the renin-angiotensin system to induce renal injury during cyclosporin A administration. More importantly, our study has identified that antagonism with PRO20 offers a novel intervention in the management of side effects of cyclosporin A.


Asunto(s)
Enfermedades Renales , Renina , Animales , Creatinina/metabolismo , Ciclosporina/toxicidad , Femenino , Humanos , Riñón/metabolismo , Enfermedades Renales/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Receptores de Superficie Celular/metabolismo , Renina/metabolismo , Sistema Renina-Angiotensina
20.
Eco Environ Health ; 1(3): 198-199, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38075600

RESUMEN

[This corrects the article DOI: 10.1016/j.eehl.2022.04.003.].

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