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1.
Pathol Res Pract ; : 152848, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32051106

RESUMO

Piwi-interacting RNAs (piRNAs) dysregulation occurs frequently in extensive cancers. However, there was no report about piRNA expression in esophageal cancer (EC). In this study, the expression levels of piR-823 and DNMT1, DNMT3A, DNMT3B were detected in 54 pairs of ESCC tissues and adjacent normal tissues using the quantitative real-time polymerase chain reaction method. Pearson's chi-squared test and receiver operating characteristic curves were established to evaluate the diagnostic and prognostic value of piR-823 in ESCC. Spearman's correlation analysis was used to evaluate the association between piR-823 and DNMTs. We found that piR-823 was significantly upregulated in ESCC tissues compared with matched normal tissues (P = 0.0213), the level of piR-823 was significantly associated with lymph node metastasis (P = 0.042). The ROC curve analysis of piR-823 expression level yielded an area under the ROC curve value of 0.713 (P = 0.0001). DNMT3B was upregulated in ESCC tissues compared with matched normal tissues (P = 0.0286). There was an obvious positive correlation between piR-823 and DNMT3B expression (r = 0.6420, P < 0.0001). In conclusion, for the first time, we provided evidence about piRNA expression in EC. piRNA-823 and DNMT3B were both upregulated in ESCC and positively correlated with each other, suggesting the tumor oncogenic role of piR-823 in ESCC to epigenetically induce aberrant DNA methylation through DNMT3B. In addition, piRNA-823 showed high specificity in detecting ESCC and higher piRNA-823 level indicated higher risk of lymph node metastasis, suggesting its diagnostic and prognostic biomarker potential.

2.
Drug Deliv ; 27(1): 283-291, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32013620

RESUMO

Discovery of novel pharmacological effects of berberine hydrochloride (BH) has made its clinical application valuable. However, further development and applications of BH are hampered by its short half-life and the side effects associated with its intravenous (iv) injection. To improve the hypolipidemia efficacy and reduce side effects, we encapsulated BH into biocompatible red blood cells (RBCs) to explore its sustained-release effect by hypotonic pre-swelling method. From in vitro evaluation, BH loaded RBCs (BH-RBCs) presented similar morphology and osmotic fragility to native RBCs (NRBCs). After the loading process, the BH-RBCs maintained around 69% of Na+/K+-ATPase activity of NRBCs and phosphatidylserine externalization value of BH-RBCs was about 26.1 ± 2.9%. The survival test showed that the loaded cells could circulate in plasma for over 9 d. For in vivo evaluation, a series of tests including pharmacokinetics study and hypolipidemic effect were carried out to examine the long-acting effect of BH-RBCs. The results showed that the release of BH in the loaded cells could last for about 5 d and the hypolipidemic effect can still be observed on 5 d after injection. BH-loaded autologous erythrocytes seem to be a promising sustained releasing delivery system with long hypolipidemic effect.

3.
Org Lett ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32052978

RESUMO

A combined approach toward syntheses of epoxyguaiane sesquiterpenes is presented. By use of a fungus sesquiterpene cyclase, guaian-6,10(14)-diene was produced through metabolic engineering of the isoprenoid pathway in E. coli. (-)-Englerin A, (-)-oxyphyllol, (+)-orientatol E, and (+)-orientalol F have been synthesized in two to six steps. This strategy provided rapid access to the epoxyguaiane core structure and would facilitate syntheses of (-)-englerin A and its analogues for evaluation of their therapeutic potentials in drug discovery.

4.
Biomed Chromatogr ; : e4806, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32012312

RESUMO

Rosmarinic acid (RA) is a phenolic acid originally isolated from the herb medicine Rosmarinus officinalis. The purpose of this study was to identify the metabolites of RA. RA was incubated with human liver microsomes in the presence of ß-nicotinamide adenine dinucleotide phosphate tetrasodium salt and/or uridine diphosphate glucuronic acid using glutathione (GSH) as a trapping agent. After 60-min incubation, the samples were analyzed using high-resolution liquid chromatography tandem mass spectrometry. Under the current conditions, 14 metabolites were detected and identified. Our data revealed that RA was metabolized through the following pathways: the first pathway is the oxidation of catechol to form ortho-quinone intermediates, which react with GSH to form mono-GSH adducts (M1, M2, and M3) and bis-GSH adducts (M4 and M5); the second pathway is conjugation with glucuronide to yield acylglucuronide (M7), which further reacts with GSH to form RA-S-acyl-GSH adduct (M9); the third pathway is hydroxylation to form M10, M11, and M12, which further react with GSH to form mono-GSH adducts (M13 and M14); the fourth pathway is conjugation with GSH through Michael addition (M6); the fifth pathway is conjugation with glucuronidation, forming M8, which is the major metabolic pathway of RA.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32057994

RESUMO

PURPOSE: Melanoma brain metastases (MBM) occur in ∼50% of melanoma patients. While both Radiation Therapy (RT) and immune checkpoint inhibitor (ICI) are used alone or in combination for MBM treatment, the role of combination and how these treatments could best be sequenced, remains unclear. METHODS AND MATERIALS: We conducted a retrospective analysis of patients with resected MBM who underwent treatment with either RT, ICI or a combination of RT and ICI. Among the latter, we specifically investigated the differential gene expression via RNA-sequencing between patients who received RT first then ICI (RT→ICI) vs. ICI first then RT (ICI→RT). We use a glycoprotein-transduced syngeneic melanoma mouse model for validation experiments. RESULTS: We find that for patients with resected MBM, combination of RT and ICI confers superior survival compared to RT alone. Specifically, we find that RT→ICI was superior compared to ICI→RT. Transcriptome analysis of resected MBM revealed that the RT→ICI cohort demonstrated deregulation of genes involved in apoptotic signaling, and key modulators of inflammation, most implicated in NFΚB signaling. In a pre-clinical model, we show that RT followed by anti-PD-L1 therapy was superior to the reverse sequence of therapy, supporting the observations we made in patients with MBM. CONCLUSIONS: Our study provides initial insights into the optimal sequence of RT and ICI in the treatment of MBM following surgical resection. Prospective studies examining the best sequence of RT and ICI are necessary and our study contributes to the rationale to pursue these.

6.
Mol Cell Endocrinol ; 505: 110742, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32006608

RESUMO

Epidemiological evidence suggests that the etiology and pathogenesis of rheumatoid arthritis (RA) are closely associated with estrogen metabolism and deficiency. Estrogen protects against articular damage. Estradiol replacement therapy ameliorates local inflammation and knee joint swelling in ovariectomized models of RA. The mechanistic basis for the protective role of 17ß-estradiol (17ß-E2) is poorly understood. Acid-sensing ion channel 1a (ASIC1a), a sodium-permeable channel, plays a pivotal role in acid-induced articular chondrocyte injury. The aims of this study were to evaluate the role of 17ß-E2 in acid-induced chondrocyte injury and to determine the effect of 17ß-E2 on the level and activity of ASIC1a protein. Results showed that pretreatment with 17ß-E2 attenuated acid-induced damage, suppressed apoptosis, and restored mitochondrial function. Further, 17ß-E2 was shown to reduce protein levels of ASIC1a through the ERα receptor, to protect chondrocytes from acid-induced apoptosis, and to induce ASIC1a protein degradation through the autophagy-lysosomal pathway. Taken together, these results show that the use of 17ß-E2 may be a novel strategy for the treatment of RA by reducing cartilage destruction through down-regulation of ASIC1a protein levels.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31965648

RESUMO

RATIONALE: Although the 2 H/1 H ratio of the carbon-bound hydrogens (C-Hs) in α-cellulose extracted from higher plants has long been used successfully for climate, environmental and metabolic studies, the assumption that bleaching with acidified NaClO2 to remove lignin before pure α-cellulose can be obtained does not alter the 2 H/1 H ratio of α-cellulose C-Hs has nonetheless not been tested. METHODS: For reliable application of the 2 H/1 H ratio of α-cellulose C-H, we processed plant materials representing different phytochemistries and photosynthetic carbon assimilation modes in isotopically contrasting bleaching media (with an isotopic difference of 273 mUr). All the isotope ratios were measured by elemental analyzer/isotope ratio mass spectrometry (EA-IRMS). RESULTS: Our results show that H from the bleaching medium does appear in the final pure α-cellulose product, although the isotopic alteration to the C-H in α-cellulose due to the incorporation of processing H from the medium is small if isotopically "natural" water is used to prepare the processing medium. However, under prolonged bleaching such an isotope effect can be significant, implying that standardizing the bleaching process is necessary for reliable 2 H/1 H measurement. CONCLUSIONS: The currently adopted method for removing lignin for α-cellulose extraction from higher plant materials with acidified NaClO2 bleaching method is considered acceptable in terms of preserving the isotopic fidelity if isotopically "natural" water is used to prepare the bleaching solution.

8.
J Neurooncol ; 146(2): 285-292, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31894518

RESUMO

PURPOSE: Patients with high rates of developing new brain metastases have an increased likelihood of dying of neurologic death. It is unclear, however, whether this risk is affected by treatment choice following failure of primary stereotactic radiosurgery (SRS). METHODS: From July 2000 to March 2017, 440 patients with brain metastasis were treated with SRS and progressed to have a distant brain failure (DBF). Eighty-seven patients were treated within the immunotherapy era. Brain metastasis velocity (BMV) was calculated for each patient. In general, the institutional philosophy for use of salvage SRS vs whole brain radiotherapy (WBRT) was to postpone the use of WBRT for as long as possible and to treat with salvage SRS when feasible. No further treatment was reserved for patients with poor life expectancy and who were not expected to benefit from salvage treatment. RESULTS: Two hundred and eighty-five patients were treated with repeat SRS, 91 patients were treated with salvage WBRT, and 64 patients received no salvage radiation therapy. One-year cumulative incidence of neurologic death after salvage SRS vs WBRT was 15% vs 23% for the low- (p = 0.06), 30% vs 37% for the intermediate- (p < 0.01), and 31% vs 48% (p < 0.01) for the high-BMV group. Salvage WBRT was associated with increased incidence of neurologic death on multivariate analysis (HR 1.64, 95% CI 1.13-2.39, p = 0.01) when compared to repeat SRS. One-year cumulative incidence of neurologic death for patients treated within the immunotherapy era was 9%, 38%, and 38% for low-, intermediate-, and high-BMV groups, respectively (p = 0.01). CONCLUSION: Intermediate and high risk BMV groups are predictive of neurologic death. The association between BMV and neurologic death remains strong for patients treated within the immunotherapy era.

9.
Oncol Rep ; 43(2): 591-600, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894331

RESUMO

Mutation of the p53 tumor suppressor frequently occurs in lung cancer, and can be as high as 75­90% in small­cell lung cancer. Mutant p53 (mtp53) can inhibit the wild­type p53 protein, disrupting its tumor suppressor functions. In addition, mutant p53 often acquires the functions of an oncogene. Post­translational modification of the p53 protein is important for its transcriptional and tumor suppressive functions. We previously revealed that high levels of mutant p53 expression were associated with reduced expression of the deacetylation enzyme sirtuin 3 (SIRT3) in lung cancer tissues. Given this negative correlation between p53 and SIRT3 expression, and given that SIRT3 is a deacetylase, we speculated that SIRT3 participates in the post­translational modification of mutant p53, regulating its stability and function, thereby inhibiting the growth of lung cancer cells. Light microscopy, MTT and flow cytometric assays revealed that SIRT3 overexpression inhibited growth and promoted apoptosis in NCI­H446 human small cell lung cancer cells. SIRT3 overexpression also resulted in necroptosis, and this could be partially reversed following cell treatment with the necroptosis inhibitor necrostatin­1 (Nec­1), which could restore certain cells to survive. Western blotting assays revealed that SIRT3 overexpression resulted in the reduced expression and half­life of mutant p53, indicating that SIRT3 decreases mutant p53 stability. Proteasome inhibitor experiments revealed that the decrease in mutant p53 stability was a result of increased proteasomal degradation of the protein. Immunoprecipitation studies revealed that ubiquitination of mutant p53 was elevated in SIRT3­overexpressing cells, indicating that SIRT3 affected ubiquitination­mediated protein degradation. In the present study, it was therefore revealed that SIRT3 can inhibit the growth of human small­cell lung cancer cells by promoting apoptosis and necroptosis. It was also revealed that SIRT3 expression could regulate the stability of mutant p53 by controlling ubiquitination­mediated proteasomal degradation of the protein. SIRT3 expression may therefore play an important role in the growth of mutant p53­associated lung cancer.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31935182

RESUMO

Strain CPCC 203383T, isolated from the surface-sterilized fruit of Cerasus pseudocerasus (Lindl.) G. Don, was taxonomically characterized based on a polyphasic investigation. It had the highest 16S rRNA gene sequence similarities with Ornithinimicrobium pekingense DSM 21552 (97.2 %) and O. kibberense DSM 17687T (97.2%). Phylogenetic analysis based on 16S rRNA gene sequences showed that the strain formed a distinct phyletic branch within the genus Ornithinimicrobium and the whole genome sequence data analyses supported that strain CPCC 203383T was phylogenetically related to the Ornithinimicrobium species. The isolate shared a range of phenotypic patterns reported for members of the genus Ornithinimicrobium, but also had a range of cultural, physiological and biochemical characteristics that separated it from related Ornithinimicrobium species. The menaquinone was MK-8(H4). The polar lipid profile consisted of diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylinositol (PI) and unidentified lipids (ULs). The major fatty acids (>5 %) were iso-C15 : 0, anteiso-C15 : 0, iso-C16:0, 9-methyl C16 : 0, iso-C17 : 0 and anteiso-C17 : 0. The cell wall peptidoglycan contains l-ornithine as diagnostic diamino acid and an interpeptide bridge consisting of L-Orn←L-Ala←Gly←D-Asp. The combined genotypic and phenotypic data indicated that the isolate represents a novel species of the genus Ornithinimicrobium, for which the name Ornithinimicrobium cerasi sp. nov. is proposed, with CPCC 203383T(=NBRC 113522T=KCTC 49200T) as the type strain. The DNA G+C composition is 72.3 mol%. The availability of new data allows for an emended description of the genus Ornithinimicrobium.

11.
Ann Surg Oncol ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980985

RESUMO

BACKGROUND: Appendiceal mucinous neoplasm (AMN) with peritoneal metastasis is a rare but deadly disease with few prognostic or therapy-predictive biomarkers to guide treatment decisions. Here, we investigated the prognostic and biological attributes of gene expression-based AMN molecular subtypes. METHODS: AMN specimens (n = 138) derived from a population-based subseries of patients treated at our institution with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) between 05/2000 and 05/2013 were analyzed for gene expression using a custom-designed NanoString 148-gene panel. Signed non-negative matrix factorization (sNMF) was used to define a gene signature capable of delineating robustly-classified AMN molecular subtypes. The sNMF class assignments were evaluated by topology learning, reverse-graph embedding and cross-cohort performance analysis. RESULTS: Three molecular subtypes of AMN were discerned by the expression patterns of 17 genes with roles in cancer progression or anti-tumor immunity. Tumor subtype assignments were confirmed by topology learning. AMN subtypes were termed immune-enriched (IE), oncogene-enriched (OE) and mixed (M) as evidenced by their gene expression patterns, and exhibited significantly different post-treatment survival outcomes. Genes with specialized immune functions, including markers of T-cells, natural killer cells, B-cells, and cytolytic activity showed increased expression in the low-risk IE subtype, while genes implicated in the promotion of cancer growth and progression were more highly expressed in the high-risk OE subtype. In multivariate analysis, the subtypes demonstrated independent prediction power for post-treatment survival. CONCLUSIONS: Our findings suggest a greater role for the immune system in AMN than previously recognized. AMN subtypes may have clinical utility for predicting CRS/HIPEC treatment outcomes.

12.
J Colloid Interface Sci ; 564: 134-142, 2020 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-31911219

RESUMO

The metal (Fe/Co), nitrogen co-doped carbon represent an important class of oxygen reduction reaction (ORR), which can be obtained via the thermal treatment of transition-metal macrocycles (TMMs). However, the N4-chelate complex with metal atom (M-N4) moieties as major activity site for ORR are easily destroyed to form inorganic metal species during simple pyrolysis of TMMs. In this report, polyacrylonitrile (PAN) nanofibers were prepared by electrospinning containing a small amount of hemin (chloroprotoporphyrin IX iron(III), TMMs). The electrospun nanofibers were converted into Fe, N co-doped carbon nanofibers (Fe-N-CNFs) through preoxidized and thermal treatment. The PAN macromolecules can prevent hemin from aggregation during the process of pyrolysis. The Fe elemental mapping demonstrated that Fe species probably existed in a single atom state. The Fe K-edge X-ray absorption fine structure spectrum of Fe-N-CNFs proved that the Fe-N4 moieties have been successfully reserved. The X-ray photoelectron spectra of Fe-N-CNFs indicated that the amount of Fe-N4 moieties increased with the increased percent of hemin. Therefore, the Fe-N-CNFs exhibited the higher catalytic activity for ORR compared with Pt electrocatalysts. Furthermore, the Fe1-N-CNFs displayed higher stability and methanol tolerance than Pt/C.

13.
Eur J Pharmacol ; 871: 172916, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31930970

RESUMO

Macrophages play important roles in the healing and remodeling of cardiac tissues after myocardial ischemia/reperfusion (MI/R) injury. Here we investigated the potential effects of salvianolic acid B (SalB), one of the abundant and bioactive compounds extracted from Chinese herb Salvia Miltiorrhiza (Danshen), on macrophage-mediated inflammation after MI/R and the underlying mechanisms. In primary cultured bone marrow-derived macrophages (BMDMs), SalB attenuated lipopolysaccharide (LPS)-induced M1 biomarkers (IL-6, iNOS, CCL2 and TNF-α) mRNA expression in a concentration-dependent manner. In contrast, M2 biomarkers (Arg1, Clec10a and Mrc) mRNA levels following interleukinin-4 (IL-4) stimulation were significantly upregulated by SalB. In addition, LPS stimulation potently induced transcriptional upregulation of RagD, an important activation factor of mammalian target of rapamycin complex 1 (mTORC1). Interestingly, SalB inhibited RagD upregulation and mTORC1 activation, decreased glycolysis, and reduced inflammatory cytokine production in LPS-stimulated macrophages, all of which were blunted in RagD knockdown macrophages. In mice subjected to MI/R, SalB treatment decreased cardiac M1-macrophages and increased M2-macrophages at 3 days post-MI/R, followed by decreased collagen deposition and ameliorated cardiac dysfunction at 7 days post-MI/R. Collectively, our data have shown that SalB decreases M1-polarized macrophages in MI/R hearts via inhibiting mTORC1-dependent glycolysis, which might contribute to alleviated inflammation and improved cardiac dysfunction afforded by SalB after MI/R.

14.
Int Immunopharmacol ; 80: 106181, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31926446

RESUMO

Saikosaponin-d (SSd), a triterpenoid saponins compound extracted from Radix Bupleuri, has been demonstrated to effectively alleviate chronic mild stress-induced depressive behaviors in rats, but the underlying molecular mechanisms are still uncertain. Increasing evidence indicated that microglia activation and inflammatory responses were involved in the pathogenesis of depression. Thus, we desired to induce inflammation-related depressive-like behaviors in mice by injecting lipopolysaccharide (LPS) to investigate whether the antidepressant effect of SSd is related to inhibiting inflammation. The results of behavioral tests showed that SSd administration ameliorated LPS-induced depressive-like behaviors, as shown by increased sucrose consumption in the sucrose preference test and decreased immobility time in the tail suspension test and forced swimming test. Furthermore, immunostaining results showed that SSd pretreatment inhibited LPS-induced microglia activation in the hippocampus of mice and primary microglia cells. Enzyme-linked immunosorbent assay (ELISA) results showed that SSd pretreatment suppressed LPS-induced overexpression of inflammatory factors such as interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α both in vivo and in vitro. Immunostaining and western blot analysis results demonstrated that SSd pretreatment also inhibited LPS-induced HMGB1 translocation from nuclear to extracellular and decreased the protein levels of TLR4, p-IκB-α, NF-κBp65. These results suggested that SSd effectively improved LPS-induced inflammation-related depressive-like behaviors by inhibiting LPS-induced microglia activation and neuroinflammation, and the possible mechanism might associate with the regulation of the HMGB1/TLR4/NF-κB signaling pathway.

15.
Bioorg Med Chem Lett ; 30(2): 126795, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31759850

RESUMO

High throughput screening for ß-lactamase inhibitors afforded biphenyl hits such as 1. Hit confirmation and X-ray soaking experiments with Pseudomonas Aeruginosa AmpC enzyme led to the identification of an aryl boronic acid-serine complex 4, which was formed from phenyl boronic acid 8 (an impurity in compound 1) and ethylene glycol (the cryoprotectant in the soaking experiment).

16.
J Craniofac Surg ; 31(1): e73-e75, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31634308

RESUMO

Cutaneous lymphangioma circumscriptum (CLC) is an uncommon congenital lymphatic malformation. Its dermoscopic features have been reported, however, if blood has infiltrated the lacunas, a pink hue overwhelms the lacunar structures, rendering dermoscopic features indistinguishable. In addition, dermoscopy cannot assess the subcutaneous extent of the lesion before surgery. The high-frequency array transducer Sonography with a high-frequency transducer is excellent in its resolution to evaluate skin lesions and is unaffected by infiltration of blood. Here, the authors report the use of ultrasound (color Doppler and pulse wave Doppler) for the diagnosis and management of CLC.An 18-year-old man presented 10 years previously with an asymptomatic 0.5 × 0.7 cm cluster of dark reddish vesicular lesions on his buttock. The lesions had recently increased in size and number. There was associated pachyderma. The lesions were hyperechoic and well defined on grayscale ultrasound and hypervascular on color Doppler ultrasound. Cluster cystics of lymphatic spaces were found throughout the whole dermis, especially in the papillary dermis. The lymphatic channels extended downwards to the reticular dermis and the superficial layer of the subcutaneous tissue. The pathological findings revealed lymphangiomas invading the subcutaneous tissue. The flat endothelial cells were partly positive for D2-40, which is a marker of lymphatic endothelial cells. Ultrasound was able to delineate the margins of the lesions. Diagnosis of CLC using preoperative color Doppler and pulse wave Doppler could reduce unnecessary repeated pre- and postoperative biopsies.

17.
J Hazard Mater ; 384: 121461, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31685320

RESUMO

Sulfur-containing materials are very attractive for the efficient decontamination of some heavy metals. However, the effective and irreversible removal of Cd2+, coupled with a high uptake efficiency, remains a great challenge due to the relatively low bond dissociation energy of CdS. Herein, we propose a new strategy to overcome this challenge, by the incorporation of Cd2+ into a stable ZnxCd1-xS solid solution, rather than into CdS. This can be realised through the adsorption of Cd2+ by ZnS nanoparticles, which have exhibited a Cd2+ uptake capacity of approximate 400 mg g-1. Through this adsorption mechanism, the Cd2+ concentration in a contaminated solution could effectively be reduced from 50 ppb to <3 ppb, a WHO limit acceptable for drinking water. In addition, ZnS continued to exhibit this noteworthy uptake capacity even in the presence of Cu2+, Pb2+, and Hg2+. ZnS displayed high chemical stability. Particles aged in air for 3 months still retained a> 80% uptake capacity for Cd2+, compared with only 9% uptake capacity for similarly-aged FeS particles. This work reveals a new mechanism for Cd2+ removal with ZnS and establishes a valuable starting point for further studies into the formation of solid solutions for hazardous heavy metal removal applications.

18.
Stem Cells ; 38(2): 261-275, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31721342

RESUMO

The tunica adventitia ensheathes arteries and veins and contains presumptive mesenchymal stem cells (MSCs) involved in vascular remodeling. We show here that a subset of human adventitial cells express the CD10/CALLA cell surface metalloprotease. Both CD10+ and CD10- adventitial cells displayed phenotypic features of MSCs when expanded in culture. However, CD10+ adventitial cells exhibited higher proliferation, clonogenic and osteogenic potentials in comparison to their CD10- counterparts. CD10+ adventitial cells increased expression of the cell cycle protein CCND2 via ERK1/2 signaling and osteoblastogenic gene expression via NF-κB signaling. CD10 expression was upregulated in adventitial cells through sonic hedgehog-mediated GLI1 signaling. These results suggest that CD10, which marks rapidly dividing cells in other normal and malignant cell lineages, plays a role in perivascular MSC function and cell fate specification. These findings also point to a role for CD10+ perivascular cells in vascular remodeling and calcification.

19.
Br J Pharmacol ; 177(2): 432-448, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31655022

RESUMO

BACKGROUND AND PURPOSE: Growing evidence indicates targeting mitochondrial dynamics and biogenesis could accelerate recovery from renal ischemia-reperfusion (I/R) injury, but the underlying mechanisms remain elusive. Transcription factor forkhead box O1 (FOXO1) is a key regulator of mitochondrial homeostasis and plays a pathological role in the progression of renal disease. EXPERIMENTAL APPROACH: A mouse model of renal I/R injury and a hypoxia/reoxygenation (H/R) injury model for human renal tubular epithelial cells were used. KEY RESULTS: I/R injury up-regulated renal expression of FOXO1 and treatment with FOXO1-selective inhibitor AS1842856 prior to I/R injury decreased serum urea nitrogen, serum creatinine and the tubular damage score after injury. Post-I/R injury AS1842856 treatment could also ameliorate renal function and improve the survival rate of mice following injury. AS1842856 administration reduced mitochondrial-mediated apoptosis, suppressed the overproduction of mitochondrial ROS and accelerated recovery of ATP both in vivo and in vitro. Additionally, FOXO1 inhibition improved mitochondrial biogenesis and suppressed mitophagy. Expression of PPAR-γ coactivator 1α (PGC-1α), a master regulator of mitochondrial biogenesis, was down-regulated in both I/R and H/R injury, which could be abrogated by FOXO1 inhibition. Experiments using integrated bioinformatics analysis and coimmunoprecipitation established that FOXO1 inhibited PGC-1α transcription by competing with cAMP-response element binding protein (CREB) for its binding to transcriptional coactivators CREBBP/EP300 (CBP/P300). CONCLUSION AND IMPLICATIONS: These findings suggested that FOXO1 was critical to maintain mitochondrial function in renal tubular epithelial cells and FOXO1 may serve as a therapeutic target for pharmacological intervention in renal I/R injury.

20.
Inorg Chem ; 59(1): 161-171, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31498603

RESUMO

Bis[o-(trifluoromethyl)phenyl]dithiophosphinate is a sulfur-donating ligand capable of providing the largest reported trivalent lanthanide (Ln3+)-actinide (An3+) group separation factors. Literature has shown that the placement and number of the -CF3 functionalities on the aryl rings proximate to the ligating sulfur atoms can significantly impact Ln3+-An3+ extraction and separation factors, but the complexation thermodynamics of -CF3-derivatized aryldithiophosphinates have not been considered to date. This systematic study considers the complexation of three CF3-substituted aryldithiophosphinates-bis(phenyl)dithiophosphinate (LI), [o-(trifluoromethyl)phenyl](phenyl)dithiophosphinate (LII), and bis[o-(trifluoromethyl)phenyl]dithiophosphinate (LIII), with Nd3+ in an ethanolic environment. The chelating ability of NdIII by these ligands follows the order of LIII > LII > LI, which is in line with the reported extraction efficiency. The positive ΔS, as well as positive ΔH, suggests that Nd3+ chelation is entropy-driven and effective desolvation is critical to enabling Nd3+ interaction with otherwise weakly interacting sulfur-containing ligands. Extended X-ray absorption fine structure results confirm thermodynamic investigations and suggest that LI can only form up to 1:2 (M-L) complexes, while LII and LIII form up to 1:3 complexes with Nd3+. All three LIII anions have bidentate interactions with NdIII, but two LII anions have bidentate interactions with Nd3+, while the third LII anion is monodentate. The significant increase in ΔS with each o-CF3 addition suggests aiding desolvation could be central in enabling f-element interaction with weakly interacting donor groups, and this report provides an approach to controlling f-element desolvation as an innovative f-element chelating strategy.

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