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1.
J Hazard Mater ; 393: 122390, 2020 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-32114130

RESUMEN

Iron oxide nanoparticles (IONPs), commonly occurring in soils, aquifers and subsurface sediments, may serve as important electron shuttles for the biotransformation of coexisting toxic metals. Here, we explored the impact of different IONPs (low-crystallinity goethite and ferrihydrite, high-crystallinity magnetite and hematite) on the reduction of Cu(II) by Geobacter sulfurreducens and the associated electron shuttle mechanisms. All four IONPs tested can function as electron shuttles to enhance long distance electron transfer from bacteria to Cu(II). Upon IONPs addition, the rate of Cu(II) reduction increased from 14.9 to 65.0-83.8 % in solution after 7 days of incubation. Formation of both Cu(I) and Cu(0) on the iron oxide nanoparticles was revealed by the X-ray absorption near-edge spectroscopy. The IONPs can be utilized as conduits by bacteria to directly transfer electrons and they can also reversibly accept and donate electrons as batteries through a charging-discharging cycle to transfer electron. The latter mechanism (geo-battery) played an important role in all four types of IONPs while the former one (geo-conductor) can only be found in the magnetite and hematite treatments due to the higher crystallinity. Our results shed new light on the biogeochemically mediated electron flux in microbe-IONPs-metal networks under anaerobic iron-reduction conditions.

2.
Ecotoxicol Environ Saf ; 194: 110411, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32151869

RESUMEN

Accidental ingestion of Pb-contaminated soil particles by direct hand-to-mouth activity or by swallowing airborne dust particles is important pathway of human exposure to Pb. Appropriate evaluation of Pb risk to human is important in determining whether the soil needs remediation or not, however, there is paucity of data about the dietary influences on Pb bioaccessibility (Pb-BA) and transformation in humans. This study chose two typical foods, spinach and cola, representing vegetable and soft drink, respectively, and investigated their effects on Pb species in gastrointestinal tract using the physiologically based extraction test. Results showed that ingestion of spinach and cola decreased the Pb-BA by 52%-94% in the gastric phase and by 38%-95% in the intestinal phase, respectively. The reduction of Pb-BA by spinach was attributed to the precipitation of Pb with phosphorus in spinach and the sorption of Pb by the generated hydrolysate and un-hydrolysate from spinach in gastrointestinal tract. Cola decreased Pb-BA mainly via formation of insoluble Pb phosphates precipitates. Analysis of X-ray diffraction and MINTEQ modeling demonstrated that the dissolved Pb was transformed to precipitated or sorbed Pb with intake of cola or spinach. Our findings suggest that dietary habit greatly influence the speciation and subsequent Pb-BA in the gastrointestinal tract, which should be incorporated into human health risk assessment of Pb-contaminated soil.

3.
Talanta ; 212: 120799, 2020 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-32113561

RESUMEN

A novel amine- and carboxyl-bifunctionalized organic-inorganic hybrid monolithic column (A&C-HMC) was synthesized via one-pot co-condensation of N-(2-aminoethyl)-3-aminopropyltriethoxysilane, carboxyethylsilanetriol sodium salt and tetramethoxysilane with cetyltrimethylammonium bromide and polyethylene glycol 6000 as binary porogens in this work. The introduction of the binary porogens controllably improved the morphology and pore structure of A&C-hybrid monolith (HM) and made the active sites of amine and carboxyl groups more prolific, compared with the monolith prepared with either of porogens. It is found that Cr(VI) and Cr(III) can be selectively adsorbed on A&C-HM under different pH ranges, and eluted by aqueous nitric acid solution completely. The A&C-HMC was used as needle-solid phase microextraction (SPME) matrix for direct separation and enrichment of inorganic chromium species coupled with inductively coupled plasma mass spectrometer without any oxidation/reduction treatment. Various parameters of SPME operation and analytical performance were investigated systematically, and the adsorption mechanism was also discussed and explained in depth. In view of the advantages of facile preparation, low cost, excellent speciation selectivity and high adsorption capacity to Cr(VI) and Cr(III), the A&C-HMC based SPME protocol is a promising alternative for non-disturbed speciation analysis of inorganic chromium in real environmental water samples.

4.
Cell Death Dis ; 11(3): 167, 2020 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-32127525

RESUMEN

Pseudogenes have long been considered as nonfunctional genomic sequences. Recent studies have shown that they can potentially regulate the expression of protein-coding genes and are dysregulated in diseases including cancer. However, the potential roles of pseudogenes in ovarian cancer have not been well studied. Here we characterized the pseudogene expression profile in HGSOC (high-grade serous ovarian carcinoma) by microarray. We identified 577 dysregulated pseudogenes and most of them were up-regulated (538 of 577). HMGA1P6 (High mobility group AT-hook 1 pseudogene 6) was one of the overexpressed pseudogenes and its expression was inversely correlated with patient survival. Mechanistically, HMGA1P6 promoted ovarian cancer cell malignancy by acting as a ceRNA (competitive endogenous RNA) that led to enhanced HMGA1 and HMGA2 expression. Importantly, HMGA1P6 was transcriptionally activated by oncogene MYC in ovarian cancer. Our findings reveal that MYC may contribute to oncogenesis through transcriptional regulation of pseudogene HMGA1P6 in ovarian cancer.

5.
Sensors (Basel) ; 20(6)2020 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-32178463

RESUMEN

Image classification is a fundamental task in remote sensing image processing. In recent years, deep convolutional neural networks (DCNNs) have experienced significant breakthroughs in natural image recognition. The remote sensing field, however, is still lacking a large-scale benchmark similar to ImageNet. In this paper, we propose a remote sensing image classification benchmark (RSI-CB) based on massive, scalable, and diverse crowdsourced data. Using crowdsourced data, such as Open Street Map (OSM) data, ground objects in remote sensing images can be annotated effectively using points of interest, vector data from OSM, or other crowdsourced data. These annotated images can, then, be used in remote sensing image classification tasks. Based on this method, we construct a worldwide large-scale benchmark for remote sensing image classification. This benchmark has large-scale geographical distribution and large total image number. It contains six categories with 35 sub-classes of more than 24,000 images of size 256 × 256 pixels. This classification system of ground objects is defined according to the national standard of land-use classification in China and is inspired by the hierarchy mechanism of ImageNet. Finally, we conduct numerous experiments to compare RSI-CB with the SAT-4, SAT-6, and UC-Merced data sets. The experiments show that RSI-CB is more suitable as a benchmark for remote sensing image classification tasks than other benchmarks in the big data era and has many potential applications.

6.
J Cell Physiol ; 2020 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-32180229

RESUMEN

Glioblastoma (GBM) is the most malignant primary brain tumor in adults. Due to its invasive nature, it cannot be thoroughly eliminated. WD repeat domain 12 (WDR12) processes the 32S precursor rRNA but cannot affect the synthesis of the 45S/47S primary transcript. In this study, we found that WDR12 is highly expressed in GBM according to the analysis results of mRNA expression by The Cancer Genome Atlas database. The high expression level of WDR12 is dramatically related to shorter overall survival and reduced disease-free survival. Next, we knocked down WDR12 and found that knockdown of WDR12 promoted the apoptosis and inhibited the proliferation by cell biology experiments. Differential expression genes in gene-chip revealed that WDR12 knockdown mainly inhibited cell cycle. Finally, we also found that WDR12 is associated with PLK1 and EZH2 in cell proliferation of GBM. Resumptively, this report showed a possible evidence that WDR12 drove malignant behavior of GBM, whose expression may present a neoteric independent prognostic biomarker in GBM.

7.
Infect Dis Poverty ; 9(1): 17, 2020 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-32114982

RESUMEN

BACKGROUND: Dengue is a re-emerging public health problem and mosquito-borne infectious disease that is transmitted mainly by Aedes aegypti and Ae. albopictus. Early diagnosis, isolation, and treatment of patients are critical steps for dengue epidemic control, especially to prevent secondary transmission of dengue virus (DENV). However, little is known about defervescent dengue patients as a source of infection. METHODS: This case study describes 1268 dengue patients hospitalized at Guangzhou Eighth People's Hospital from June 2013 to December 2014. The viral loads of each individual were measured using real-time reverse transcription-polymerase chain reaction. Ae. aegypti and Ae. albopictus were exposed to blood meal with gradated dengue viral loads to characterize the relationship between viremia in dengue patients and the vector competence of vector mosquitoes. RESULTS: The viral numbers in the blood were measured, ranging from 108 to 103 copies/ml from day 1 to day 12 after fever onset. Vector competence analysis of Ae. aegypti and Ae. albopictus indicated that viremia > 104 copies/ml can still infect vector mosquitoes, which implied that the defervescent dengue patients might be a source of infection. CONCLUSIONS: The results of this study indicate that some defervescent dengue patients still have sufficient viral load to infect vector mosquitoes. Therefore, the protection against mosquito biting for these people should be extended to prevent secondary transmission events.


Asunto(s)
Virus del Dengue/fisiología , Dengue/epidemiología , Dengue/transmisión , Mosquitos Vectores/virología , Aedes/virología , Animales , Virus del Dengue/aislamiento & purificación , Humanos , Carga Viral
8.
Expert Opin Drug Deliv ; : 1-11, 2020 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-32149539

RESUMEN

Introduction: Many active ingredients from natural plants (AINPs) have been revealed to possess remarkable anticancer properties. Combination chemotherapy of chemo-drugs and AINPs has also proven to be more advantageous than individual chemo-drug treatment with respect to enhancing efficiency, alleviating toxicity, and controlling the development of multidrug resistance (MDR). Co-delivery is considered a promising method to effectively achieve and manage combination chemotherapy of chemo-drugs and AINPs, and various distinctive and functional co-delivery systems have been designed for these purposes to date.Areas covered: This review focuses on recent preclinical investigations of co-delivery systems for chemo-drugs and AINPs as new cancer treatment modalities. We particularly emphasize the apparent treatment advantages of these approaches, including augmenting efficiency, reducing toxicity, and controlling MDR.Expert opinion: There has already been notable progress in the application of combination chemotherapy with co-delivery systems loaded with chemo-drugs and AINPs based on results with cellular and animal models. The main challenge is to translate these successes into new anticancer compound preparations and promote their clinical application in practice. Nevertheless, continuous efforts with new designs of co-delivery systems remain essential, providing a foundation for future clinical research and development of new anticancer drugs.

9.
Hum Mutat ; 2020 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-32126152

RESUMEN

Alexander disease results from gain-of-function mutations in the gene encoding glial fibrillary acidic protein (GFAP). At least eight GFAP isoforms have been described, however, the predominant alpha isoform accounts for ∼90% of GFAP protein. We describe exonic variants identified in three unrelated families with Type II Alexander disease that alter the splicing of GFAP pre-messenger RNA (mRNA) and result in the upregulation of a previously uncharacterized GFAP lambda isoform (NM_001363846.1). Affected members of Family 1 and Family 2 shared the same missense variant, NM_001363846.1:c.1289G>A;p.(Arg430His) while in Family 3 we identified a synonymous variant in the adjacent nucleotide, NM_001363846.1:c.1290C>A;p.(Arg430Arg). Using RNA and protein analysis of brain autopsy samples, and a mini-gene splicing reporter assay, we demonstrate both variants result in the upregulation of the lambda isoform. Our approach demonstrates the importance of characterizing the effect of GFAP variants on mRNA splicing to inform future pathophysiologic and therapeutic study for Alexander disease.

10.
Contraception ; 2020 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-32135125

RESUMEN

OBJECTIVES: To calculate the minimum fetal red blood cell concentration required to cause maternal Rh sensitization; validate the use of a flow cytometry protocol below that concentration; preliminarily assess the concentrations of fetal red blood cells in pregnant women before and after uterine aspiration. STUDY DESIGN: Using pre-existing literature, we calculated the lowest concentration of fetal red blood cells found to cause sensitization within adult female circulation. We validated a two-color flow cytometry protocol using fluorescently labeled antibodies to Hemoglobin F (expressed by fetal red blood cells and adult F cells) and Carbonic Anhydrase (expressed in red blood cells during the third trimester and postnatally) by titrating second trimester cord blood into non-pregnant adult blood. We applied this flow cytometry protocol in a prospective cohort study of 42 pregnant women at 5 to 12 weeks gestational age undergoing uterine aspiration for induced or spontaneous abortion. RESULTS: The calculated threshold for causing Rh sensitization was 250 fetal red blood cells per 10 million total red blood cells. We showed a linear relationship between observed and expected fetal red blood cell fractions in titrated samples. Fetal red blood cell counts were more reliable when samples acquired by flow cytometry contained at least 1 million red blood cells. All 37 subjects with evaluable paired samples demonstrated fetal red blood cell concentrations below the calculated threshold for Rh sensitization both pre- and post-procedure. The fetal RBC concentrations increased from a mean of 4.5 (median 0, range 0-57) fetal RBCS pre- to a mean of 8.6 (median 2, range 0-32) fetal RBCs post- per 10 million total RBCs (p<0.001). CONCLUSIONS: Flow cytometry was capable of separately quantifying fetal red blood cells and maternal F cells to very dilute concentrations. Fetal red blood cell exposure in the first trimester was well below the calculated threshold for maternal Rh sensitization in our cohort. Larger studies are warranted to confirm our pilot study findings, fill this evidence gap and inform universal guidelines for administering Rh immunoglobulin after first trimester uterine aspiration.

11.
Sci Total Environ ; 719: 137410, 2020 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-32120099

RESUMEN

Understanding the role played by autochthonous functional microbes involved in the biotransformation of pollutants would help optimize bioremediation performance at contaminated sites. However, our knowledge of the remediation potential of indigenous diazotrophs in contaminated soils remains inadequate. Using a microcosm experiment, soil nitrogen fixation activity was manipulated by molybdenum (Mo) and tungsten (W), and their effect on the removal of polycyclic aromatic hydrocarbons (PAHs) was determined in agricultural and industrial soils. Results showed that after 42 days of incubation, PAH dissipation efficiency was significantly enhanced by 1.06-fold in 600 µg kg-1 Mo-treated agricultural soil, compared with that in the control. For the industrial soil, 1200 µg kg-1 Mo treatment significantly promoted PAH removal by 90.76% in 21 days, whereas no significant change was observed between treatments and control at the end of the incubation period. W also exerted a similar effect on PAH dissipation. The activity and gene abundance of nitrogenase were also increased under Mo/W treatments in the two soils. Spearman's correlation analysis further indicated that removal of PAHs was positively correlated with nitrogenase activity in soil, which could be due to the elevated abundances of PAH-degrading genes (PAH-RHDα) in these treatments. Our results suggest the importance of autochthonous diazotrophs in PAH-contaminated soils, which indicates a feasible and environmentally friendly biostimulation strategy of manipulating nitrogen fixation capacity.

12.
Int J Biol Macromol ; 152: 718-726, 2020 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-32126201

RESUMEN

Colorectal peritoneal carcinomatosis (CRPC) is an advanced stage of colorectal cancer (CRC), which significantly decreases patient survival and quality of life. Here, the naturally occurring polysaccharide hyaluronic acid (HA) was used to prepare an injectable hydrogel and simultaneously deliver 5-fluorouracil (5-FU), cisplatin (DDP) and paclitaxel (PTX) microspheres for intraperitoneal CRPC chemotherapy. The drug-loaded HA hydrogel released the drugs in a sustained manner, and showed low toxicity both in vitro and in a mouse model of CRPC. Furthermore, direct injection of the drug-loaded HA hydrogel in the abdominal cavity of tumor-bearing mice significantly decreased tumor growth and liver/lung metastasis, along with decreasing the volume of ascites and inhibiting local intestinal infiltration of the tumor cells. Therefore, this novel multi-drug hydrogel delivery system may effectively clear CRPC tumors without any adverse effects when used in intraperitoneal chemotherapy.

13.
Drug Des Devel Ther ; 14: 715-730, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32158191

RESUMEN

Introduction: Enrofloxacin is used in the treatment of a wide variety of bacterial infections in mammals. However, its poor solubility limits the clinical use. Methods: In order to improve the solubility of enrofloxacin, the enrofloxacin mesylate (EM) were obtained by a chemical synthesis method. The characterization of EM was carried out using ultraviolet scan (UV), synchronous thermal analysis (SDT), fourier transform infrared spectrometer (FTIR) and mass spectrometry (MS), nuclear magnetic resonance (NMR) and X-ray powder diffraction analysis (XRPD). Acute toxicity of EM in Kunming mice was studied. Besides, pharmacokinetic studies were performed in New Zealand rabbits at a single oral dose of 10 mg/kg, and the antibacterial activity of EM was also evaluated. Results: EM was successfully synthesized and purified. The stoichiometric ratio of mesylate to enrofloxacin was 1:1 and the aqueous solubility of EM was 483.01±4.06 mg/mL, the solubility of EM was about 2000 times higher than enrofloxacin. The oral lethal dose (LD50) of EM was 1168.364 mg/kg, and the pharmacokinetics indicated that the oral relative bioavailability of EM was about 1.79 times and 1.48 times higher than that of enrofloxacin and enrofloxacin hydrochloride, respectively. In addition, the in vitro antibacterial activity of EM was not significantly changed compared with enrofloxacin and enrofloxacin hydrochloride. Conclusion: EM has higher solubility, low toxicity for oral use, and increases the oral bioavailability in rabbit. This study may be of benefit for the development of new enrofloxacin drugs.

14.
Artículo en Inglés | MEDLINE | ID: mdl-32169560

RESUMEN

BACKGROUND: Schizophrenia (SCZ) is a highly heritable disorder associated with brain connectivity changes. Although the mechanism of disease expression and vulnerability of SCZ have been reported by previous studies, the mechanism of resilience to SCZ based on the brain structural connectivity is poorly understood. The goal of the present study was to identify the structural brain connectivity related with the resilience to SCZ, which is defined here as the capacity to avoid or delay the onset of SCZ in unaffected siblings of SCZ probands. METHOD: We collected diffusion tensor imaging (DTI) data of 49 medication-naive, first-episode SCZ (FE-SCZ) patients, 56 unaffected siblings of SCZ probands (SIB-SCZ), and 90 healthy controls. Then we used graph theoretical approach to calculate the topological properties of the brain structural network, including global, subnetwork, and regional parameters. Finally, we compared the parameters between the three groups, and identified the brain structural network related to the resilience, vulnerability and disease expression to SCZ. RESULTS: With respect to resilience, only the SIB-SCZ showed significantly increased connectivity in the subnetworks of the left cuneus-precuneus and left posterior cingulate gyrus-precuneus, and in brain areas of right supramarginal gyrus and right inferior temporal gyrus. With respect to vulnerability, both the FE-SCZ and SIB-SCZ had decreased cluster coefficients and local efficiency, and decreased nodal efficiency in the right medial superior frontal gyrus and right medial orbital superior frontal gyrus compared with the healthy controls. With respect to disease expression, only the FE-SCZ group showed decreased or increased global, subnetwork, and nodal connectivity in broader brain regions compared with the healthy controls. CONCLUSION: Difference in the topological properties of brain structural connectivity not only reflect the underlying mechanism of vulnerability but also that of resilience to schizophrenia. Alteration in the brain structural connectivity associating with resilience and disease expression may contribute to the onset of SCZ.

15.
Cell Death Dis ; 11(3): 181, 2020 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-32165613

RESUMEN

Fatty acids are the most major substrate source for adult cardiac energy generation. Prohibitin 2 (PHB2), a highly conserved protein located in mitochondrial inner membrane, plays key roles in cellular energy metabolic homeostasis. However, its functions in regulating cardiac fatty acid metabolism have remained largely unknown. Our study demonstrates that cardiac-specific knockout of Phb2 leads to accumulation of lipid droplets and causes heart failure. Mechanistically, ablation of PHB2 impairs cardiac fatty acid oxidation (FAO) through downregulating carnitine palmitoyltransferase1b (CPT1b), a rate-limiting enzyme of cardiac mitochondrial FAO. Moreover, overexpression of CPT1b alleviates impaired FAO in PHB2-deficient cardiomyocytes. Thus, our study provides direct evidence for the link between PHB2 and cardiac fatty acid metabolism. Our study points out that PHB2 is a potential FAO regulator in cardiac mitochondrial inner membrane, as well as the connection between PHB2 and CPT1b and their relationships to cardiac pathology especially to cardiac fatty acid metabolic disorder.

16.
Sci Total Environ ; 716: 137120, 2020 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-32059321

RESUMEN

LiAl hydrotalcite-like compound (LiAl HTlc) was synthesized via a hydrothermal method and used to adsorb Cu2+ and Zn2+ for investigating the adsorption characteristics of heavy metal cations. The X-Raydiffraction (XRD), fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM) and transmission electron microscopy (TEM) characterizations revealed the interconnecting flower-like layered structure of LiAl HTlc. The adsorption kinetics and isotherms of Cu2+ and Zn2+ on LiAl HTlc agreed with the pseudo-second-order model and the Langmuir model at a given sorbent concentration (Cs), respectively. The Cs-effect on the adsorption kinetics and isotherms was observed, and the Langmuir-surface component activity (SCA) equation could be utilized to characterize the effect of Cs in the adsorption isotherms. The adsorption process was spontaneous and endothermic. The adsorption mechanism denoted that the adsorption process was controlled using two main mechanisms, i.e., surface complexation and isomorphic substitution. This is the first report, to the best of our knowledge, on the usage of LiAl HTlc for the removal of heavy metal cations Cu2+ and Zn2+ from a solution. LiAl HTlc is a promising sorbent for treating water containing heavy metal cations.

17.
J Am Chem Soc ; 142(12): 5636-5648, 2020 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-32077695

RESUMEN

A significant enhancement in the Menshutkin SN2 reaction between 1-methylimidazole (MeIm) and methyl thiocyanate (MeSCN) is observed when the reaction is confined in the nanoscale silica pores of MCM41 and SBA15. The experiments in the silica pores are conducted without the surrounding bulk reaction mixture. The influences of temperature, pore radius, and surface chemistry on the kinetics of the confined reaction are analyzed with time-dependent infrared spectroscopy, molecular dynamics simulations, and ab initio calculations. The rate constant of the pseudo-first order reaction increases with decreasing pore size, and the activation energy is found to decrease by 5.6 kJ/mol in the smallest pore studied (2.8 nm) relative to the bulk reaction. The rate constant dependence on pore size is accurately described by a two-state model in which molecules within the 4.6 Å interfacial layer experience a 2.4-fold rate constant increase relative to those reacting at the bulk rate further away from the interface. The removal of polar silanol groups from the silica surface via passivation with trimethylsilyl chloride results in bulk-like kinetics despite a reduction in the pore diameter, demonstrating the role of silanols as catalytic sites. Electronic structure calculations of the energy profile on a model silica surface confirm that silanol groups, particularly those of the vicinal type, can reduce the activation energy and reaction endothermicity through the donation of hydrogen bonds to the reactant, transition state, and product complexes.

18.
J Diabetes Res ; 2020: 6286571, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32104713

RESUMEN

Ischemic postconditioning (PC) is proved to efficiently protect diabetic patients with acute myocardial infarction from ischemia-reperfusion injury. We aimed to explore the protective roles of ischemic PC on diabetic retinopathy in tree shrews with diabetic cerebral ischemia. A diabetic tree shrew model was established through high-fat diet feeding combined with streptozotocin (STZ) injection, while cortical thrombotic cerebral ischemia was induced photochemically. Tree shrews were divided into the normal control group, sham operation group, diabetes mellitus group, diabetes mellitus+cerebral ischemia group, and diabetes mellitus+cerebral ischemia+PC group (in which the tree shrews with diabetic cerebral ischemia were treated with ischemic PC). H&E staining was used to examine the pathological changes in the retina, and immunohistochemistry was performed to determine the retinal expression of VEGF (vascular endothelial growth factor). The modeling resulted in 77% tree shrews with diabetes. Ischemic PC reduced the blood glucose levels in the tree shrews with diabetic cerebral ischemia. Tree shrews with diabetes had thinned retina with disordered structures, and these pathological changes were aggravated after cerebral ischemia. The retinopathy was alleviated after ischemic PC. Retina expression of VEGF was mainly distributed in the ganglion cell layer in tree shrews. Diabetes and cerebral ischemia increased retinal VEGF expression in a step-wise manner, while additional ischemic PC reduced retinal VEGF expression. Therefore, ischemic PC effectively alleviates retinopathy in tree shrews with diabetic cerebral ischemia, and this effect is associated with reduced retinal VEGF expression.

19.
BMC Complement Med Ther ; 20(1): 7, 2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32020868

RESUMEN

BACKGROUND: As the dry rhizome of Anemone raddeana Regel, Rhizoma Anemones Raddeanae (RAR), which belongs to Ranunculaceae, is usually used to treat wind and cold symptoms, hand-foot disease and spasms, joint pain and ulcer pain in China. It is well known that the efficacy of RAR can be distinctly enhanced by processing with vinegar due to the reduced toxicity and side effects. However, the entry of vinegar into liver channels can cause a series of problems. In this paper, the differences in the acute toxicity, anti-inflammatory and analgesic effects between RAR and vinegar-processed RAR were compared in detail. The changes in the chemical compositions between RAR and vinegar-processed RAR were investigated, and the mechanism of vinegar processing was also explored. METHODS: Acute toxicity experiments were used to examine the toxicity of vinegar-processed RAR. A series of studies, such as the writhing reaction, ear swelling experiment, complete Freund's adjuvant-induced rat foot swelling experiment and cotton granuloma, in experimental mice was conducted to observe the anti-inflammatory effect of vinegar-processed RAR. The inflammatory cytokines of model rats were determined by enzyme-linked immunosorbent assay (ELISA). Liquid Chromatography-Quadrupole-Time of Flight mass spectrometer Detector (LC-Q-TOF) was used to analyse the chemical compositions of the RARs before and after vinegar processing. RESULTS: Neither obvious changes in mice nor death phenomena were observed as the amount of vinegar-processed RAR in crude drug was set at 2.1 g/kg. Vinegar-processed RAR could significantly prolong the latency, reduce the writhing reaction time to reduce the severity of ear swelling and foot swelling, and remarkably inhibit the secretion of Interleukin-1ß(IL-1ß), Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) proinflammatory cytokines. The content of twelve saponins (e.g., Eleutheroside K) in RAR was decreased after vinegar processing, but six other types (e.g., RDA) were increased. CONCLUSIONS: These results revealed that vinegar processing could not only improve the analgesic and anti-inflammatory effects of RAR but also reduce its own toxicity. TRIAL REGISTRATION: Not applicable.

20.
Proc Natl Acad Sci U S A ; 117(8): 4328-4336, 2020 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-32029582

RESUMEN

Epigenetic alterations and metabolic dysfunction are two hallmarks of aging. However, the mechanism of how their interaction regulates aging, particularly in mammals, remains largely unknown. Here we show ELOVL fatty acid elongase 2 (Elovl2), a gene whose epigenetic alterations are most highly correlated with age prediction, contributes to aging by regulating lipid metabolism. Impaired Elovl2 function disturbs lipid synthesis with increased endoplasmic reticulum stress and mitochondrial dysfunction, leading to key accelerated aging phenotypes. Restoration of mitochondrial activity can rescue age-related macular degeneration (AMD) phenotypes induced by Elovl2 deficiency in human retinal pigmental epithelial (RPE) cells. We revealed an epigenetic-metabolism axis contributing to aging and potentially to antiaging therapy.

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