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1.
Anesthesiology ; 140(4): 690-700, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38150544

RESUMEN

BACKGROUND: Propofol is an intravenous anesthetic associated with hypotension, respiratory depression, and injection-site pain. HSK3486 injectable emulsion (ciprofol) is a 2,6-disubstituted phenol derivative with fast onset and quick, stable recovery. Previous studies support HSK3486 as an effective, safe anesthetic with substantially less injection-site pain than propofol. The primary objective of this study was to investigate the noninferiority of HSK3486 compared with propofol in successful general anesthesia induction. METHODS: Two hundred fifty-five participants were enrolled in HSK3486-304, a multicenter, randomized (2:1), double-blind, propofol-controlled, phase 3 study evaluating HSK3486 for general anesthesia induction in adults undergoing elective surgery with tracheal intubation. The primary endpoint was successful anesthesia induction, defined as 1 or less on the Modified Observer's Assessment of Alertness/Sedation scale. Key secondary endpoints were proportion of participants with injection-site pain on the Numerical Rating Scale of 1 or greater and a composite endpoint, including the proportion of participants successfully induced while maintaining the desired anesthetic depth and without substantial cardiac and respiratory events. Safety endpoints included adverse events, abnormal vital signs, and injection-site pain. RESULTS: Two hundred fifty-one participants (HSK3486, n = 168; propofol, n = 83) were included in the analyses. General anesthesia was successfully induced in 97.0% versus 97.6% of participants with HSK3486 and propofol, respectively. The difference in success rate was -0.57% (95% CI, -5.4 to 4.2%); the noninferiority boundary of -8% was not crossed. Thirty participants (18.0%) had injection-site pain with HSK3486 versus 64 (77.1%) with propofol (P < 0.0001). Eighty-one participants (48.2%) with HSK3486 versus 42 (50.6%) with propofol (P = 0.8780) satisfied the composite endpoint. When injection-site pain was excluded, the incidence of treatment-emergent adverse events related to study drug was 17.9% for HSK3486 and 14.5% for propofol. CONCLUSIONS: The study met its primary objective and endpoint, demonstrating noninferiority of HSK3486 compared with propofol in successful anesthetic induction. Substantially less injection-site pain was associated with HSK3486 than with propofol.


Asunto(s)
Hipotensión , Propofol , Adulto , Humanos , Propofol/efectos adversos , Anestésicos Intravenosos/efectos adversos , Dolor/tratamiento farmacológico , Anestesia General/efectos adversos , Hipotensión/complicaciones , Método Doble Ciego
2.
J Formos Med Assoc ; 121(3): 613-622, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34332829

RESUMEN

BACKGROUND: Healthcare personnel (HCP) at the front line of care are exposed to occupational hazards that place them at risk for infection, which then endanger patient safety and compromise the capability of the healthcare workforce. As of March 8, 2021 more than 420,170 HCP in US had been infected with SARS CoV-2 with 1388 deaths. In two Taiwan hospitals COVID-19 outbreaks involved HCP and resulted in shutdown of service. This report describes our prospective health surveillance of the HCP and COVID-19 containment measures in a teaching hospital in Taiwan during Jan. 1 through June 30, 2020. METHODS: We prospectively monitored incidents, defined as an HCP with the predefined symptoms, reported by HCP through the web-based system. HCP were managed based on an algorithm that included SARS CoV-2 RNA PCR testing. Infection prevention and control policy/practice were reviewed. RESULTS: This hospital took care of 17 confirmed COVID-19 cases during the study period and the first Case was admitted on January 23, 2020. Among the 14,210 HCP, there were 367 incident events. Of 283 HCP tested for SARS CoV-2, 179 had predefined symptoms. These included 10 HCP who met the national case definition for COVID-19 infection and 169 based on Extended COVID-19 Community Screening program. The other 104 asymptomatic HCP were tested based on hospital policy. All of them had tested negative. CONCLUSION: We attribute our success in preventing COVID-19 infections among HCP to rapid, proactive, decisive, integrated national and institutional response in the early stages of the epidemic.


Asunto(s)
COVID-19 , Centros Médicos Académicos , COVID-19/epidemiología , COVID-19/prevención & control , Personal de Salud , Humanos , Estudios Prospectivos , SARS-CoV-2 , Taiwán/epidemiología
3.
J Chem Phys ; 155(7): 074701, 2021 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-34418937

RESUMEN

We studied the dissociation of water (H2O*, with * denoting adspecies) on atomic oxygen (O*)-covered Rh nanoclusters (RhO* ) supported on a graphene film grown on a Ru(0001) surface [G/Ru(0001)] under ultrahigh-vacuum conditions and with varied surface-probe techniques and calculations based on density-functional theory. The graphene had a single rotational domain; its lattice expanded by about 5.7% to match the Ru substrate structurally better. The Rh clusters were grown by depositing Rh vapors onto G/Ru(0001); they had an fcc phase and grew in (111) orientation. Water adsorbed on the Rh clusters was dissociated exclusively in the presence of O*, like that on a Rh(111) single-crystal surface. Contrary to the case on Rh(111)O* , excess O* (even at a saturation level) on small RhO* clusters (diameter of 30-34 Å) continued to promote, instead of inhibiting, the dissociation of water; the produced hydroxyl (OH*) increased generally with the concentration of O* on the clusters. The difference results from more reactive O* on the RhO* clusters. O* on RhO* clusters activated the dissociation via both the formation of hydrogen bonds with H2O* and abstraction of H directly from H2O*, whereas O* on Rh(111)O* assisted the dissociation largely via the formation of hydrogen bonds, which was readily obstructed with an increased O* coverage. As the disproportionation (2 OH* → H2O* + O*) is endothermic on the RhO* clusters but exothermic on Rh(111)O* , OH* produced on RhO* clusters showed a thermal stability superior to that on the Rh(111)O* surface-thermally stable up to 400 K.

4.
Int J Mol Sci ; 22(11)2021 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-34072831

RESUMEN

Although histone deacetylase 8 (HDAC8) plays a role in glioblastoma multiforme (GBM), whether its inhibition facilitates the treatment of temozolomide (TMZ)-resistant GBM (GBM-R) remains unclear. By assessing the gene expression profiles from short hairpin RNA of HDAC8 in the new version of Connectivity Map (CLUE) and cells treated by NBM-BMX (BMX)-, an HDAC8 inhibitor, data analysis reveals that the Wnt signaling pathway and apoptosis might be the underlying mechanisms in BMX-elicited treatment. This study evaluated the efficacy of cotreatment with BMX and TMZ in GBM-R cells. We observed that cotreatment with BMX and TMZ could overcome resistance in GBM-R cells and inhibit cell viability, markedly inhibit cell proliferation, and then induce cell cycle arrest and apoptosis. In addition, the expression level of ß-catenin was reversed by proteasome inhibitor via the ß-catenin/ GSK3ß signaling pathway to reduce the expression level of c-Myc and cyclin D1 in GBM-R cells. BMX and TMZ cotreatment also upregulated WT-p53 mediated MGMT inhibition, thereby triggering the activation of caspase-3 and eventually leading to apoptosis in GBM-R cells. Moreover, BMX and TMZ attenuated the expression of CD133, CD44, and SOX2 in GBM-R cells. In conclusion, BMX overcomes TMZ resistance by enhancing TMZ-mediated cytotoxic effect by downregulating the ß-catenin/c-Myc/SOX2 signaling pathway and upregulating WT-p53 mediated MGMT inhibition. These findings indicate a promising drug combination for precision personal treating of TMZ-resistant WT-p53 GBM cells.


Asunto(s)
Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Glioblastoma/tratamiento farmacológico , Histona Desacetilasas/genética , Proteínas Represoras/genética , Proteína p53 Supresora de Tumor/genética , Proteínas Supresoras de Tumor/genética , beta Catenina/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioblastoma/genética , Glioblastoma/patología , Humanos , Proteínas Represoras/antagonistas & inhibidores , Bibliotecas de Moléculas Pequeñas/farmacología , Temozolomida/efectos adversos , Temozolomida/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto
5.
J Pharmacol Sci ; 138(1): 46-53, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30245287

RESUMEN

Hepatic steatosis is the early stage of alcoholic liver disease (ALD), may progress to steatohepatitis, fibrosis even cirrhosis. Polydatin, the primary active component of Polygonum cuspidatum Sieb. et Zucc, has been recognized to possess hepatoprotective and anti-inflammatory properties. To investigate whether polydatin alleviates ethanol induced liver injury and to elucidate the underlying molecular mechanisms, zebrafish larvae at 4 days post-fertilization (dpf) were exposed to 350 mmol/L of ethanol for 32 h, then treated with polydatin for 48 h. Oil red O, Nile Red and H&E staining were used to analyze the pathological changes in liver. The mRNA levels were measured by quantitative PCR and the antioxidant capacity was detected using H2O2-specific fluorescent probe. Here, polydatin strongly alleviated hepatic steatosis and decreased the expression levels of alcohol and lipid metabolism-related genes, including CYP2Y3, CYP3A65, HMGCRa, HMGCRb and FASN. Additionally, polydatin inhibited oxidative stress in the liver according to fluorescent probe. Moreover, significantly up-regulated expression of DNA damage-related genes (CHOP, GADD45αa) revealed that polydatin attenuated hepatic apoptosis in larvae. In conclusion, polydatin may improve the liver function of zebrafish with acute alcoholic liver injury through attenuating hepatic fat accumulation, ameliorating lipid and ethanol metabolism and reducing oxidative stress and DNA damage.


Asunto(s)
Antiinflamatorios , Antioxidantes , Glucósidos/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Hepatopatías Alcohólicas/tratamiento farmacológico , Hepatopatías Alcohólicas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fitoterapia , Estilbenos/farmacología , Pez Cebra , Animales , Hidrocarburo de Aril Hidroxilasas/genética , Hidrocarburo de Aril Hidroxilasas/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Familia 3 del Citocromo P450/genética , Familia 3 del Citocromo P450/metabolismo , Daño del ADN/genética , Fallopia japonica/química , Expresión Génica/efectos de los fármacos , Glucósidos/aislamiento & purificación , Glucósidos/uso terapéutico , Metabolismo de los Lípidos/genética , Hepatopatías Alcohólicas/genética , Hepatopatías Alcohólicas/patología , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Oxidorreductasas N-Desmetilantes/genética , Oxidorreductasas N-Desmetilantes/metabolismo , Estilbenos/aislamiento & purificación , Estilbenos/uso terapéutico , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo
6.
Phys Chem Chem Phys ; 20(2): 1261-1266, 2018 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-29250624

RESUMEN

The dissociation of water molecules absorbed on a cleaved non-polar GaN(11[combining macron]00) surface was studied primarily with synchrotron-based photoemission spectra and density-functional-theory calculations. The adsorbed water molecules are spontaneously dissociated into hydrogen atoms and hydroxyl groups at either 300 or 130 K, which implies a negligible activation energy (<11 meV) for the dissociation. The produced H and OH were bound to the surface nitrogen and gallium on GaN(11[combining macron]00) respectively. These results highlight the promising applications of the non-polar GaN(11[combining macron]00) surface in water dissociation and hydrogen generation.

7.
Phys Chem Chem Phys ; 19(22): 14566-14579, 2017 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-28537293

RESUMEN

Self-organized alloying of Au with Rh in nanoclusters on an ordered thin film of Al2O3/NiAl(100) was investigated via various surface probe techniques under ultrahigh-vacuum conditions and calculations based on density-functional theory. The bimetallic clusters were formed on the sequential deposition of vapors of Au and Rh onto Al2O3/NiAl(100) at 300 K. The formation was more effective on the oxide seeded with Rh, since all post-deposited Au joined the pregrown Rh clusters; for metal deposition in the reverse order, some separate Rh clusters were formed. The contrasting behavior is rationalized through the easier nucleation of Rh on the oxide surface, due to the stronger Rh-oxide and Rh-Rh bonds. The alloying in the clusters proceeded, regardless of the order of metal deposition, toward a specific structure: an fcc phase, (100) orientation and Rh core-Au shell structure. The orientation, structural ordering and lattice parameters of the Au-Rh bimetallic clusters resembled Rh clusters, rather than Au clusters, on Al2O3/NiAl(100), even with Rh in a minor proportion. The Rh-predominated core-shell structuring corresponds to the binding energies in the order Rh-Rh > Rh-Au > Au-Au. The core-shell segregation, although active, was somewhat kinetically hindered, since elevating the sample temperature induced further encapsulation of Rh. The bimetallic clusters became thermally unstable above 500 K, for which both Rh and Au atoms began to diffuse into the substrate. Moreover, the electronic structures of surface elements on the bimetallic clusters, controlled by both structural and electronic effects, show a promising reactivity.

8.
J Imaging Inform Med ; 37(1): 209-229, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38343263

RESUMEN

The purpose of this study is to predict the mRNA expression of CSF1R in HGG non-invasively using MRI (magnetic resonance imaging) omics technology and to evaluate the correlation between the established radiomics model and prognosis. We investigated the predictive value of CSF1R in the Cancer Genome Atlas (TCGA) and The Cancer Imaging Archive (TCIA) database. The Support vector machine (SVM) and the Logistic regression (LR) algorithms were used to create a radiomics_score (Rad_score), respectively. The effectiveness and performance of the radiomics model was assessed in the training (n = 89) and tenfold cross-validation sets. We further analyzed the correlation between Rad_score and macrophage-related genes using Spearman correlation analysis. A radiomics nomogram combining the clinical factors and Rad_score was constructed to validate the radiomic signatures for individualized survival estimation and risk stratification. The results showed that CSF1R expression was markedly elevated in HGG tissues, which was related to worse prognosis. CSF1R expression was closely related to the abundance of infiltrating immune cells, such as macrophages. We identified nine features for establishing a radiomics model. The radiomics model predicting CSF1R achieved high AUC in training (0.768 in SVM and 0.792 in LR) and tenfold cross-validation sets (0.706 in SVM and 0.717 in LR). Rad_score was highly associated with tumor-related macrophage genes. A radiomics nomogram combining the Rad_score and clinical factors was constructed and revealed satisfactory performance. MRI-based Rad_score is a novel way to predict CSF1R expression and prognosis in high-grade glioma patients. The radiomics nomogram could optimize individualized survival estimation for HGG patients.

9.
Heliyon ; 10(1): e23500, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38192826

RESUMEN

HOXC6 plays an essential part of the carcinogenesis of solid tumors, but its functional relevance within the immune contexture in patients with colorectal cancer (CRC) is still uncertain. We intended to investigate the predictive value of HOXC6 expression for survival outcomes and its correlation with immune contexture in CRC patients by utilizing the Cancer Genome Atlas database (n = 619). Validation was performed in cohorts from Zhongshan Hospital (n = 200) and Shanghai Cancer Center (n = 300). Immunohistochemical (IHC) staining was utilized to compare the levels of immunocytes infiltrating the tumor between the groups with high and low expression of HOXC6. Elevated levels of HOXC6 expression in CRC tissues were linked to malignant progression and poor prognosis. HOXC6 as a risk factor for survival of CRC patients was confirmed. Receiver operating characteristic analysis confirmed its diagnostic value, and a reliable prognostic nomogram was constructed. KEGG analysis and GSEA showed that HOXC6 participated in immune regulation, and its expression was tightly linked to the abundance of infiltrating immunocytes. HOXC6 was upregulated in patients diagnosed with CRC within the two cohorts, and high HOXC6 levels were correlated with a worse prognosis. The high-HOXC6 expression group showed increased infiltration of Treg cells, CD68+ macrophages, CD66b+ neutrophils, and CD8+ T-cells and elevated levels of PD-L1 and PD-1, but decreased levels of granzyme B and perforin. These findings suggest that HOXC6 abundance in patients with CRC determines a poor prognosis, promotes an immunoevasive environment, and directs CD8+ T-cell dysfunction. HOXC6 is expected to become a prospective biomarker for the outcome of CRC.

10.
Ann Med ; 56(1): 2394584, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39183455

RESUMEN

BACKGROUND: With the decline of global fertility, drug therapeutic of ectopic pregnancy is of great significance. Lithospermum erythrorhizon is using for embryo killing as herbal medicine. Shikonin is the critical nucleus of Lithospermum erythrorhizon; however, the mechanism is still unclear. The study aimed to explore the mechanism of shikonin against ectopic pregnancy. MATERIAL AND METHODS: In this study, we examined the viability and LDH release of HTR-8/SVneo cells by assays, observed pore formation in cell membranes by microscopy imaging and PI staining, and IL-1ß release by WB and ELISA assay kit. Then, we used network pharmacology to analyse the potential interaction between shikonin, ectopic pregnancy and pyroptosis and used molecular docking techniques to verify interactions between shikonin and core common targets. Finally, western blotting and immunofluorescence assay were used to explore the mechanism of shikonin-inducing pyroptosis of HTR-8/SVneo cells. RESULTS: Shikonin could cause a significant inhibition of HTR-8/SVneo cell viability in a concentration- and time-dependent manner. In HTR-8/SVneo cells, shikonin-induced cell swelling, bubble formation, an increase in the release of lactate dehydrogenase (LDH) and up-regulation of several pyroptosis-associated factors. And network pharmacology showed that The main targets of shikonin-ectopic pregnancy-pyroptosis were IL-1ß and caspase-1, and molecular docking results showed that shikonin can closely bind to IL-1ß, caspase-1 and GSDMD. Additionally, the necroptosis inhibitor GSK'872 could not suppress the expression of mature-IL-1ß and prevent the pyroptosis phenotype from developing. However, the nucleotide oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inhibitor MCC-950 could downregulate the expression of pyroptosis-associated factors and prevent the pyroptosis phenotype from developing. Shikonin led to an elevation in the expression of cathepsin B (CTSB), and the CTSB inhibitor CA-074 abolished pyroptosis induced by shikonin; however, the NLRP3 inhibitor MCC-950 could not inhibit the expression of CTSB. CONCLUSIONS: Our results suggest that shikonin activates CTSB to induce NLRP3-dependent pyroptosis in HTR-8/SVneo cells. This study has important clinical implications for the treatment of ectopic pregnancy.


Asunto(s)
Inflamasomas , Lithospermum , Simulación del Acoplamiento Molecular , Proteína con Dominio Pirina 3 de la Familia NLR , Naftoquinonas , Piroptosis , Trofoblastos , Naftoquinonas/farmacología , Humanos , Piroptosis/efectos de los fármacos , Lithospermum/química , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Trofoblastos/efectos de los fármacos , Trofoblastos/metabolismo , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Femenino , Embarazo , Línea Celular , Interleucina-1beta/metabolismo , Supervivencia Celular/efectos de los fármacos , Farmacología en Red
11.
Nat Commun ; 15(1): 653, 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38253575

RESUMEN

Transition metal dichalcogenides, by virtue of their two-dimensional structures, could provide the largest active surface for reactions with minimal materials consumed, which has long been pursued in the design of ideal catalysts. Nevertheless, their structurally perfect basal planes are typically inert; their surface defects, such as under-coordinated atoms at the surfaces or edges, can instead serve as catalytically active centers. Here we show a reaction probability > 90 % for adsorbed methanol (CH3OH) on under-coordinated Pt sites at surface Te vacancies, produced with Ar+ bombardment, on layered PtTe2 - approximately 60 % of the methanol decompose to surface intermediates CHxO (x = 2, 3) and 35 % to CHx (x = 1, 2), and an ultimate production of gaseous molecular hydrogen, methane, water and formaldehyde. The characteristic reactivity is attributed to both the triangular positioning and varied degrees of oxidation of the under-coordinated Pt at Te vacancies.

12.
ACS Appl Mater Interfaces ; 15(12): 16153-16161, 2023 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-36802501

RESUMEN

Layered transition metal dichalcogenides (TMDs) are two-dimensional materials exhibiting a variety of unique features with great potential for electronic and optoelectronic applications. The performance of devices fabricated with mono or few-layer TMD materials, nevertheless, is significantly affected by surface defects in the TMD materials. Recent efforts have been focused on delicate control of growth conditions to reduce the defect density, whereas the preparation of a defect-free surface remains challenging. Here, we show a counterintuitive approach to decrease surface defects on layered TMDs: a two-step process including Ar ion bombardment and subsequent annealing. With this approach, the defects, mainly Te vacancies, on the as-cleaved PtTe2 and PdTe2 surfaces were decreased by more than 99%, giving a defect density <1.0 × 1010 cm-2, which cannot be achieved solely with annealing. We also attempt to propose a mechanism behind the processes.

13.
Biomed Pharmacother ; 156: 113743, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36252358

RESUMEN

Ovarian damage and infertility are the main side effects of chemotherapy for women of childbearing age with cancer. The main objective of this study was to investigate the protective effects and mechanisms of hyperoside against cyclophosphamide (Cy) -induced ovarian damage and reduced fertility. This study consists of two parts: in vivo experiments using Cy intraperitoneal injections to simulate clinical chemotherapy sessions and in vitro experiments using 4-HC, a precursor of an activated form of Cy, to intervene in human granulosa-like cell line (KGN). We found that Cy disrupted the estrous cycle in mice, resulting in decreased serum Anti-Mullerian hormone (AMH) levels, loss of primordial follicles, primary follicle and secondary follicle, increased atretic follicles, and diminished ovarian reserve function. Cy prolonged the time between mating and pregnancy in mice and increased the number of absorbed embryos. Western Blot analysis demonstrate that Cy activated key proteins of HIF-1α/BNIP3-associated autophagy both in vivo and in vitro, while in vivo experiments we also found that 4-HC increased KGN cell apoptosis, damaged mitochondrial membrane potential, and activated autophagic flow. Co-treatment with hyperoside diminished follicular depletion of the primordial follicles, decreased follicular atresia, prevented Cy-induced excessive hypoxia and autophagy activation, increased mitochondrial membrane potential, thereby increasing follicular reserve and rescuing fertility in Cy-treated mice. It suggests that HIF-1α/BNIP3-mediated autophagy is an essential mechanism by which Cy impairs ovarian function and fertility in mice, by blocking this activation, hyperoside shows potential as an ovarian protectant that may be capable of preserving fertility in women undergoing chemotherapy.


Asunto(s)
Atresia Folicular , Folículo Ovárico , Animales , Femenino , Humanos , Ratones , Embarazo , Autofagia , Ciclofosfamida/toxicidad , Proteínas de la Membrana/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas Proto-Oncogénicas/metabolismo
14.
Drug Des Devel Ther ; 16: 2083-2099, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35800255

RESUMEN

Background: Albeit oxidative stress has been implied in the pathogenesis of tubal pregnancy (TP), there are scant data to suggest that ferroptosis occurs in TP. Shikonin plays a pivotal role in redox status, but whether it can regulate ferroptosis to treat TP remains unknown. Methods: We collected and analyzed ferroptosis-related indices from the villous tissue (VT) of women suffering from TP and from women with a normal pregnancy. In vitro, we used shikonin and/or RAS-selective lethal 3 (RSL3) to intervene HTR-8/SVneo cells and further detected ferroptosis indices and cell functions. Finally, the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) is pharmacologically activated to explore the effect of Nrf2 on shikonin regulating ferroptosis. Results: Increased malondialdehyde content, reduced levels of glutathione and glutathione peroxidase (GPx), and upregulated protein expression which promoted ferroptosis were observed in the VT of TP patients, suggesting that ferroptosis occurred during TP. In vitro, shikonin enhanced ferroptosis sensitivity in HTR-8/SVneo cells induced by RSL3 via amplifying lipid peroxidation, which mainly included increasing cellular reactive oxygen species (ROS), lipid ROS and Fe2+ level. RSL3 and/or shikonin inhibited Nrf2 and downregulated protein expression of SLC7A11 and GPx4 caused by RSL3 + shikonin co-treatment, which could be reversed under activation of Nrf2. Hence, shikonin facilitated lipid peroxidation by inhibiting Nrf2 signaling. Additionally, shikonin and/or RSL3 potently inhibited the invasion and migration of HTR-8/SVneo cells. Conclusion: This study firstly showed that ferroptosis may be involved in TP pathogenesis and shikonin potentially targeted ferroptosis to treat TP.


Asunto(s)
Ferroptosis , Embarazo Tubario , Carbolinas/farmacología , Muerte Celular , Femenino , Humanos , Factor 2 Relacionado con NF-E2/metabolismo , Naftoquinonas , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Especies Reactivas de Oxígeno/metabolismo
15.
ACS Appl Mater Interfaces ; 14(14): 16901-16910, 2022 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-35357129

RESUMEN

Organic-molecular magnets based on a metal-organic framework with chemically tuned electronic and magnetic properties have been attracting tremendous attention due to their promising applications in molecular magnetic sensors, magnetic particle medicines, molecular spintronics, etc. Here, we investigated the magnetic behavior of a heterojunction comprising a ferromagnetic nickel (Ni) film and an organic semiconductor (OSC) 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4-TCNQ) layer. Through the magneto-optical Kerr effect (MOKE), a photoemission electron microscopy (PEEM), X-ray magnetic circular dichroism (XMCD), and X-ray photoelectron spectroscopy (XPS), we found that the adsorption of F4-TCNQ on Cu(100)/Ni not only reverses the in-plane magnetization direction originally exhibited by the Ni layer but also results in enhanced magnetic ordering. Furthermore, the cyano group (CN) in adsorbed F4-TCNQ was found spin-polarized along with conspicuous charge transfer with Ni. The density functional theory (DFT) calculations suggest that the experimentally found spin polarization originates from hybridization between the CN group's π orbitals and Ni's d band. These findings signify that the hybrid states at the organic-ferromagnet interface play a key role in tailoring the magnetic behavior of interfaces. For the case of the F4-TCNQ and Ni heterojunction reported here, interface coupling is an antiferromagnetic one.

16.
Artículo en Inglés | MEDLINE | ID: mdl-35783512

RESUMEN

Asperosaponin VI (AS6), as the quality marker of Dipsaci Radix, is verified to exert therapeutic effect on alleviating recurrent spontaneous abortion (RSA). However, due to the lack of relevant research, its molecular mechanism is still unclear. We retrieved targets for AS6 and RSA, and then used their overlapped targets for PPI analysis. In addition, we used GO and KEGG enrichment analyses, and molecular docking to investigate the anti-RSA mechanisms of AS6. Furthermore, we conducted in vitro experiments to validate the predictions of network pharmacology. Results showed that a total of 103 AS6-associated targets and 2084 RSA-associated targets, with 49 targets overlapped. GO enrichment analysis showed 845 significant biological processes like decidualization, while KEGG pathway enrichment analysis revealed 76 significant entries including 18 signaling pathways, which were closely linked to PI3K-Akt, HIF-1, TNF, IL-17, and VEGF signaling pathways, etc. Molecular docking findings verified that AS6 had tight link with the key targets including JUN, CASP3, STAT3, SRC, and PTGS2. Notably, in vitro experiments revealed that AS6 treatment could exert lower expressions of JUN, pro-CASP3, CASP3, STAT3, SRC, and PTGS2 in decidual cells compared with progesterone despite the expressions of STAT3, SRC, and PTGS2 with no significant difference, and mifepristone could interfere with the effects. In general, numerous targets and multiple pathways involve during the process of AS6 treatment against RSA. Moreover, our in vitro research first reported that AS6 may regulate the expressions of key targets (JUN, CASP3, STAT3, SRC, and PTGS2) in decidual cells to promote decidualization, thus treating RSA.

17.
RSC Adv ; 11(40): 24762-24771, 2021 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-35481058

RESUMEN

Annealed Rh nanoclusters on an ordered thin film of Al2O3/NiAl(100) were shown to exhibit a promoted reactivity toward the decomposition of methanol-d4, under both ultrahigh vacuum and near-ambient-pressure conditions. The Rh clusters were grown with vapor deposition onto the Al2O3/NiAl(100) surface at 300 K and annealed to 700 K. The decomposition of methanol-d4 proceeded only through dehydrogenation, with CO and deuterium as products, on Rh clusters both as prepared and annealed. Nevertheless, the catalytic reactivity of the annealed clusters, measured with the production of either CO or deuterium per surface Rh site from the reaction, became at least 2-3 times that of the as-prepared ones. The promoted reactivity results from an altered support effect associated with an annealing-induced mass transport at the surface. Our results demonstrate a possibility to practically prepare reactive Rh clusters, regardless of the cluster size, that can tolerate an elevated reaction temperature, with no decreased reactivity.

18.
Phys Rev Lett ; 104(17): 177204, 2010 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-20482136

RESUMEN

To emulate the interfacial regimes of a Co/Pc/Co spin-valve structure, we fabricated ultrathin pentacene/cobalt (Pc/Co) and cobalt/pentacene (Co/Pc) bilayers. Through measurement of the magneto-optical Kerr effect, we found the Co layer has its magnetic properties depend strongly upon the order of deposition. Further x-ray spectroscopy and microscopy investigation indicated Co/Pc was chemically stable, whereas Pc/Co was reactive and exhibited complex magnetization pattern. The different chemistry and magnetic configurations at interfaces could cause additional complication for spin injection.

19.
Reprod Toxicol ; 95: 104-112, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32461113

RESUMEN

Unruptured ectopic pregnancy (UEP) is a common cause of morbidity and, occasionally, of mortality in women of reproductive age. Pharmacological intervention is a common therapeutic approach for early-stage UEP. Herein, we investigated the cytotoxic effect and novel mechanism of shikonin, a natural naphthoquinone pigment purified from Lithospermum erythrorhizon, in human trophoblast cells. These data demonstrated that shikonin suppressed proliferation and induced apoptosis in a time-dependent manner in HTR-8/SVneo cells. Shikonin blocked autophagic flux and promoted p62 interaction with caspase 8, resulting in caspase 8 activation. Moreover, shikonin suppressed GLI1 expression, and GLI1 overexpression attenuated shikonin-induced cell apoptosis. Although silencing GLI1 slightly promoted cell apoptosis, p62 overexpression enhanced GLI1 silencing-induced cell apoptosis by activating caspase 8. Furthermore, rapamycin increased shikonin-induced cell apoptosis in HTR-8/SVneo cells, whereas 3-MA attenuated the cytotoxic effect of shikonin. In conclusion, shikonin suppressed trophoblast cell growth by silencing GLI1 and increasing p62 co-mediated activation of caspase 8, which suggested a potential novel therapeutic target for UEP.


Asunto(s)
Naftoquinonas/farmacología , Trofoblastos/efectos de los fármacos , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Caspasa 8/metabolismo , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Humanos , Proteínas de Unión al ARN/metabolismo , Trofoblastos/metabolismo , Proteína con Dedos de Zinc GLI1/genética , Proteína con Dedos de Zinc GLI1/metabolismo
20.
RSC Adv ; 10(30): 17787-17794, 2020 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-35515600

RESUMEN

We have studied the reforming reaction of ethanol co-adsorbed with atomic oxygen (O*, * denotes adspecies) and deuterated water (D2O*) on a Rh(111) surface, with varied surface probe techniques under UHV conditions and with density-functional-theory calculations. Adsorbed ethanol molecules were found to penetrate readily through pre-adsorbed water, even up to eight overlayers, to react at the Rh surface; they decomposed at a probability promoted by the water overlayers. The production probabilities of H2, CO, CH2CH2 and CH4 continued to increase with co-adsorbed D2O*, up to two D2O overlayers, despite separate increasing rates; above two D2O overlayers, those of H2, CO and CH2CH2 were approximately saturated while that of CH4 decreased. The increased (or saturated) production probabilities are rationalized with an increased (saturated) concentration of surface hydroxyl (OD*, formed by O* abstracting D from D2O*), whose intermolecular hydrogen bonding with adsorbed ethanol facilitates proton transfer from ethanol to OD* and thus enhances the reaction probability. The decreasing behavior of CH4 could also involve the competition for H* with the formation of H2 and HDO.

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