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1.
ACS Chem Biol ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38624108

RESUMO

Bufadienolides are a class of steroids with a distinctive α-pyrone ring at C17, mostly produced by toads and consisting of over 100 orthologues. They exhibit potent cardiotonic and antitumor activities and are active ingredients of the traditional Chinese medicine Chansu and Cinobufacini. Direct extraction from toads is costly, and chemical synthesis is difficult, limiting the accessibility of active bufadienolides with diverse modifications and trace content. In this work, based on the transcriptome and genome analyses, using a yeast-based screening platform, we obtained eight cytochrome P450 (CYP) enzymes from toads, which catalyze the hydroxylation of bufalin and resibufogenin at different sites. Moreover, a reported fungal CYP enzyme Sth10 was found functioning in the modification of bufalin and resibufogenin at multiple sites. A total of 15 bufadienolides were produced and structurally identified, of which six were first discovered. All of the compounds were effective in inhibiting the proliferation of tumor cells, especially 19-hydroxy-bufalin (2) and 1ß-hydroxy-bufalin (3), which were generated from bufalin hydroxylation catalyzed by CYP46A35. The catalytic efficiency of CYP46A35 was improved about six times and its substrate diversity was expanded to progesterone and testosterone, the common precursors for steroid drugs, achieving their efficient and site-specific hydroxylation. These findings elucidate the key modification process in the synthesis of bufadienolides by toads and provide an effective way for the synthesis of unavailable bufadienolides with site-specific modification and active potentials.

2.
Clin Neuroradiol ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489035

RESUMO

PURPOSE: Cerebral hemodynamics are important for the management of intracranial atherosclerotic stenosis (ICAS). The quantitative flow ratio (QFR) is a novel angiography-derived index for assessing the functional relevance of ICAS without pressure wires and adenosine. Good diagnostic yield with the hyperemic fractional flow reserve (FFR) have been reported, while data on the comparison of QFR to FFR are scarce. METHODS: In this prospective study 56 patients with anterior circulation symptomatic ICAS who received endovascular treatment were included. The new method of computing QFR from a single angiographic view, i.e., the Murray law-based QFR (µQFR), was applied to the examined vessels. An artificial intelligence algorithm was developed to realize the automatic delineation of vascular contour. Pressure gradients were measured before and after treatment within the lesion vessel using a pressure guidewire and the FFR was calculated. RESULTS: There was a good correlation between µQFR and FFR. Preoperative FFR predicted DWI watershed infarction (FFR optimal cut-off level: 0.755). Preoperative µQFR predicted DWI watershed infarction (µQFR optimal cut-off level: 0.51). Preoperative FFR predicted CTP hypoperfusion (FFR best predictive value: 0.62). Preoperative µQFR predicted CTP hypoperfusion (µQFR best predictive value: 0.375). CONCLUSION: The µQFR based on DSA images can be used as an indicator to assess the functional status of the lesion in patients with ICAS.

3.
Nat Commun ; 15(1): 2786, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38555287

RESUMO

Monolithic integration of novel materials without modifying the existing photonic component library is crucial to advancing heterogeneous silicon photonic integrated circuits. Here we show the introduction of a silicon nitride etch stop layer at select areas, coupled with low-loss oxide trench, enabling incorporation of functional materials without compromising foundry-verified device reliability. As an illustration, two distinct chalcogenide phase change materials (PCMs) with remarkable nonvolatile modulation capabilities, namely Sb2Se3 and Ge2Sb2Se4Te1, were monolithic back-end-of-line integrated, offering compact phase and intensity tuning units with zero-static power consumption. By employing these building blocks, the phase error of a push-pull Mach-Zehnder interferometer optical switch could be reduced with a 48% peak power consumption reduction. Mirco-ring filters with >5-bit wavelength selective intensity modulation and waveguide-based >7-bit intensity-modulation broadband attenuators could also be achieved. This foundry-compatible platform could open up the possibility of integrating other excellent optoelectronic materials into future silicon photonic process design kits.

4.
Anal Chim Acta ; 1290: 342223, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38246740

RESUMO

Photodeposited TiO2/Ag nanocomposites were generally used to be a friendly catalyst for degrading organic contaminant in environmental field. However, electrochemiluminescence (ECL) sensing analysis based on photocatalysts remains a significant challenge. Herein, polyvinylimide (PEI)-TiO2/Ag nanocomposites (PEI-TiO2/AgNCPs) film with reduced graphene oxide(r-GO) was constructed as a sensing interface for copper(II) ECL detection. TiO2/Ag nanocomposites was prepared by reversed phase microemulsion method and photodeposition technique. Moreover, it was discovered that a small amount of Cu2+ could obviously boost the ECL signal of ninhydrin-hydrogen peroxide system. Signal amplification was achieved by using the synergistic effect between r-GO and TiO2/Ag nanocomposites, and the efficiently concentrated effect of PEI to Cu2+. Furthermore, the investigation showed that ECL mechanism of ninhydrin-hydrogen peroxide system was attributed to the generated hydroxyl radical and superoxide anion during the several type of reactions. Thus for the first time, an ultrasensitive ECL approach for detecting Cu2+ could be performed using ninhydrin as an ECL signal probe and hydrogen peroxide as a co-reaction reagent. Under the suitable circumstances, the proposed method showed an excellent linear relationship in the concentration range of Cu2+ from 1.0 fM to 5.0 nM. Detection limit was estimated to be as low as 0.26 fM. The sensing interface expanded the application of photodeposited TiO2/Ag nanocomposites in ultrasensitive ECL detection. It has potential applications in other components and biological analysis.

5.
Fitoterapia ; 173: 105780, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38135092

RESUMO

In this study, 16 new ent-labdane-type diterpene glycosides, designated as goshonosides J1-J16 (1-16), along with nine previously known diterpene glycosides (17-25) were extracted from the fruits of Rubus chingii Hu. The structures of goshonosides J1-J16 were elucidated using various analytical techniques, such as nuclear magnetic resonance, electron capture detector ECD, high-resolution electrospray ionization mass spectrometry HREIMS, single-crystal X-ray diffraction, and hydrolysis. Furthermore, the isolates' efficacy in inhibiting the activity of phosphodiesterase type 5 A was evaluated. Goshonosides J1, J2, and G effectively inhibited the activity of the aforementioned enzyme (IC50 values: 6.15 ± 1.76, 3.27 ± 0.65, and 9.61 ± 2.36 µM, respectively). Our findings highlight the remarkable structural diversity of bioactive compounds in R. chingii Hu and offer insights into the use of this shrub.


Assuntos
Diterpenos , Rubus , Rubus/química , Estrutura Molecular , Glicosídeos/farmacologia , Glicosídeos/química , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5 , Diterpenos/farmacologia
6.
Food Res Int ; 173(Pt 1): 113255, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37803568

RESUMO

Rubi fructus (Rubus chingii Hu) is a fruit of Rubus genus and is used in medicine and food applications. In this study, eight new phenylpropanoids (1-8) and seven known compounds (9-15) were isolated from the dried fruits of Rubus chingii Hu, and their structures were characterized through high-resolution electrospray ionization mass spectrometry and nuclear magnetic resonance spectroscopy. Electronic circular dichroism (ECD) experiments were performed, and the results were compared with ECD spectra. Compound 3 was characterized through extensive single crystal X-ray diffraction. Evaluation of the neuroprotective pharmacological activities revealed that compounds 6, 7, 9, and 14 exerted protective effects against H2O2-induced neurotoxicity by reducing the reactive oxygen species levels at concentrations of 50 and 100 µM. Moreover, the three compounds 6, 9, and 14 significantly inhibited the expression of the Casp3 gene at a concentration of 50 µM. Compounds 7 and 9 effectively repressed the expression of the MYC gene. Compounds 6 and 9 obviously upregulated the ratio of Bcl2/Bax in SH-SY5Y cells and inhibited cell apoptosis. The study results can be used as a reference for the development of R. chingii products to realize their neuroprotective functions in the future.


Assuntos
Neuroblastoma , Fármacos Neuroprotetores , Rubus , Humanos , Extratos Vegetais/química , Neuroblastoma/metabolismo , Frutas/química , Fármacos Neuroprotetores/farmacologia , Rubus/química , Peróxido de Hidrogênio/análise
7.
Nano Lett ; 23(19): 8898-8906, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37676244

RESUMO

Photonic mechanical sensors offer several advantages over their electronic counterparts, including immunity to electromagnetic interference, increased sensitivity, and measurement accuracy. Exploring flexible mechanical sensors on deformable substrates provides new opportunities for strain-optical coupling operations. Nevertheless, existing flexible photonics strategies often require cumbersome signal collection and analysis with bulky setups, limiting their portability and affordability. To address these challenges, we propose a waveguide-integrated flexible mechanical sensor based on cascaded photonic crystal microcavities with inherent deformation and biaxial tensile state analysis. Leveraging the advanced multiplexing capability of the sensor, for the first time, we successfully demonstrate 2D shape reconstruction and quasi-distributed strain sensing with 110 µm spatial resolution. Our microscale mechanical sensor also exhibits exceptional sensitivity with a detected force level as low as 13.6 µN in real-time measurements. This sensing platform has potential applications in various fields, including biomedical sensing, surgical catheters, aircraft and spacecraft engineering, and robotic photonic skin development.

8.
Antiviral Res ; 217: 105702, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37604350

RESUMO

Coxsackievirus B3 (CVB3) is one of the major pathogens of viral myocarditis, lacking specific anti-virus therapeutic options. Increasing evidence has shown an important involvement of the miR-17-92 cluster both in virus infection and cardiovascular development and diseases, while its role in CVB3-induced viral myocarditis remains unclear. In this study, we found that miR-19a and miR-19b were significantly up-regulated in heart tissues of CVB3-infected mice and exerted a significant facilitatory impact on CVB3 biosynthesis and replication, with a more pronounced effect observed in miR-19b, by targeting the encoding region of viral RNA-dependent RNA polymerase 3D (RdRp, 3Dpol) to increase viral genomic RNA stability. The virus-promoting effects were nullified by the synonymous mutations in the viral 3Dpol-encoding region, which corresponded to the seed sequence shared by miR-19a and miR-19b. In parallel, treatment with miR-19b antagomir not only resulted in a noteworthy suppression of CVB3 replication and infection in infected cells, but also demonstrated a significant reduction in the cardiac viral load of CVB3-infected mice, resulting in a considerable alleviation of myocarditis. Collectively, our study showed that CVB3-induced cardiac miR-19a/19b contributed to viral myocarditis via facilitating virus biosynthesis and replication, and targeting miR-19a/19b might represent a novel therapeutic target for CVB3-induced viral myocarditis.


Assuntos
Enterovirus Humano B , MicroRNAs , Miocardite , Miocárdio , Replicação Viral , Enterovirus Humano B/genética , Enterovirus Humano B/fisiologia , Miocardite/metabolismo , Miocardite/virologia , Miocárdio/metabolismo , Miocárdio/patologia , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Humanos , Replicação Viral/efeitos dos fármacos , Replicação Viral/genética , Genoma Viral , RNA Polimerase Dependente de RNA/genética , Antagomirs/farmacologia , Camundongos Endogâmicos BALB C , Células HEK293 , Células HeLa , Camundongos , Animais
9.
Ther Adv Neurol Disord ; 16: 17562864231159438, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37114069

RESUMO

Background: Previous studies have shown a potential beneficial effect of endovascular therapy (EVT) in patients with acute basilar artery occlusion (BAO). It was unclear that whether atrial fibrillation (AF) can affect the clinical outcomes for BAO patients treated with EVT. Objectives: To investigate the association between AF and clinical outcomes, and whether AF can modify the efficacy and safety of EVT in patients with BAO. Design: We conducted a multicenter, nationwide, retrospective analysis to investigate how the presence of AF affects treatment allocation for BAO patients. Methods: The endovascular treatment for acute basilar artery occlusion (ATTENTION) registry was a multicenter, prospective study in China that included acute BAO patients who underwent EVT or received best medical management (BMM) between 2017 and 2021. The outcomes include the distribution of 3-month modified Rankin scale (mRS) score, functional independence (defined as mRS 0-3), symptomatic intracerebral hemorrhage, and mortality. Results: 2134 patients were included in the study, of which 619 had AF and 1515 did not have AF. The median age was 65 (interquartile range [IQR]: 56-73) years, and 689 (32.3%) patients were female. Multivariate regression analysis indicated no significant association existed between AF and the distribution of mRS (adjusted common odds ratio, 1.05 [95% CI: 0.88, 1.25]; p = 0.564) at 90 days. Similarly, AF was not found to have a significant association with and other measured outcomes, or with the effects of EVT in AF subgroups for at 90 days as measured by ordinal mRS (p for heterogeneity = 0.247). Finally, no significant differences were found for symptomatic intracerebral hemorrhage and mortality within 90 days between the EVT and BMM groups across AF subgroups. Conclusions: Our results illustrated that the effect of EVT did not differ statistically in acute ischemic stroke patients with and without AF. Moreover, no significant association between AF and functional or safety outcomes could be detected at 90 days.

10.
Heliyon ; 9(3): e13587, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36851959

RESUMO

A simple solid phase extraction (SPE) coupled with spectrophotometric method was developed for determination of trace permanganate (MnO4 -) in water. Commercial reagent polyamined-6 powder was used as SPE stationary phase to retain MnO4 - which is based on the fact that MnO4 - can be adsorbed on polyamide 6 (PA-6) sorbent as water samples flow through the SPE cartridge. 3,3',5,5'-tetramethylbenzidine (TMB) were used both as eluent solution and chromogenic agent to convert the adsorbed MnO4 - into Mn2+ and generate blue oxidized product with high molar absorptivity. Quantification of MnO4 - could be obtained by spectrophotometric detection of the resulting solution flow out of the SPE cartridge. The extraction and detection variables was optimized to maximize the absorbance of the TMB oxidized product. Under optimized conditions, this method provided linear dynamic ranges of 0.01-1 µmol L-1 for MnO4 - with preconcentration of 100 mL water sample. The limits of detection (3Sb/m) of this method in deionized water were calculated to be 5.1 nM, and the relative standard deviations were determined to be 3.2% (C = 0.1 µmol L-1, n = 5). This method has been applied to the determination of MnO4 - in spiked tap waters and satisfactory recovery was obtained.

11.
Opt Lett ; 47(20): 5272-5275, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36240340

RESUMO

This work proposed a synthetic aperture rainbow refractometry (SARR) by synthesizing rainbow signals of the same droplet with dual-wavelength laser beams, in order to increase the aperture of rainbow refractometry. In this way, the SARR can apply to long distance and small droplets measurement. An achromatic imaging system, which simultaneously records while separating the two rainbow signals in two channels of a color image, is elaborately designed. A data processing algorithm is developed to retrieve the optimal droplet refractive index and size. Numerical simulations of different droplet sizes from 10 µm to 200 µm certify the viability of the SARR. Proof-of-concept experiments of micron-sized ethanol droplets are performed with 1650 mm measurement distance. Results show that the SARR can accurately measure droplet refractive index and size with uncertainties of 2.3 × 10-4 and 2µm, respectively. The feasibility and accuracy of the proposed SARR are successfully demonstrated, paving the way for rainbow refractometry applied to large-scale industrial applications.

12.
Appl Opt ; 61(25): 7455-7462, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36256049

RESUMO

Rainbow refractometry was used to measure the temperature and size of transparent spherical particles. In practice, however, there are limitations to the application of heating and cooling droplets, as the temperature measured is neither the average nor the surface or core temperature of the droplet. Reported here is an exploitation of this technique for droplet surface temperature determination. Droplet surface tension was measured by detecting the evolution of interference fringes of oscillating droplets. The dependence of surface tension on temperature facilitated the study of surface temperature of an evaporating droplet with time. Moving ethanol, n-heptane, and n-decane droplets were investigated under heating and cooling conditions. The capabilities and limitations of rainbow refractometry were verified by comparing the droplet temperature values measured directly by rainbow refractometry with the surface temperature.

13.
Opt Lett ; 47(13): 3203-3206, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35776585

RESUMO

The astigmatic interferometric particle imaging (AIPI) model reveals that the fringe orientation shifts with droplet depth displacement, and their relationships are quantitatively formulated. The depth displacement is directly evaluated from the relative angular shift of the fringes with angular cross power spectral density, and this algorithm isolates the uncertainty of droplet depth position from depth displacement. Proof-of-concept experiments on micrometer-sized transparent droplets with a 5 kHz AIPI system demonstrates that droplet three-dimensional (3D) trajectories are accurately obtained with the accuracy of depth displacement up to tens of micrometers, improving an order of magnitude from hundreds of microns in a traditional Lagrangian framework by comparing droplet depth positions.

14.
Circulation ; 146(1): 6-17, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35656816

RESUMO

BACKGROUND: The authors compare the effectiveness and safety of endovascular treatment (EVT) versus best medical management (BMM) in strokes attributable to acute basilar artery occlusion (BAO). METHODS: The present analysis was based on the ongoing, prospective, multicenter ATTENTION (Endovascular Treatment for Acute Basilar Artery Occlusion) trial registry in China. Our analytic sample comprised 2134 patients recruited at 48 sites between 2017 and 2021 and included 462 patients who received BMM and 1672 patients who received EVT. We performed an inversed probability of treatment weighting analysis. Qualifying patients had to present within 24 hours of estimated BAO. The primary clinical outcome was favorable functional outcome (modified Rankin Scale score, 0-3) at 90 days. We also performed a sensitivity analysis with the propensity score matching-based and the instrumental variable-based analysis. RESULTS: In our primary analysis using the inversed probability of treatment weighting-based analysis, there was a significantly higher rate of favorable outcome at 90 days among EVT patients compared with BMM-treated patients (adjusted relative risk, 1.42 [95% CI, 1.19-1.65]; absolute risk difference, 11.8% [95% CI, 6.9-16.7]). The mortality was significantly lower (adjusted relative risk, 0.78 [95% CI, 0.69-0.88]; absolute risk difference, -10.3% [95% CI, -15.8 to -4.9]) in patients undergoing EVT. Results were generally consistent across the secondary end points. Similar associations were seen in the propensity score matching-based and instrumental variable-based analysis. CONCLUSIONS: In this real-world study, EVT was associated with significantly better functional outcomes and survival at 90 days. Well-designed randomized studies comparing EVT with BMM in the acute BAO are needed. REGISTRATION: URL: www.chictr.org.cn; Unique identifier: ChiCTR2000041117.


Assuntos
Arteriopatias Oclusivas , Procedimentos Endovasculares , Acidente Vascular Cerebral , Arteriopatias Oclusivas/terapia , Artéria Basilar , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Humanos , Estudos Prospectivos , Sistema de Registros , Trombectomia/métodos , Resultado do Tratamento
15.
Pharmgenomics Pers Med ; 15: 449-464, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572349

RESUMO

Background: The pathological basis of coronary heart disease (CHD) is atherosclerosis. BTNL2 can inhibit the activation of T cells. We aimed to explore the association between BTNL2 genetic variants and CHD risk in the southern Chinese Han population. Methods: We recruited 1419 participants to perform an association analysis between missense variants in BTNL2 and CHD risk through SNPStats online software. Genotyping of all candidate SNPs were completed by the Agena MassARRAY. In addition, we used false-positive report probability analysis to detect whether the positive findings were noteworthy observations. We also used Haploview 4.2 software and SNPStats online software to conduct the haplotype analysis and analysis of linkage disequilibrium (LD). Finally, the interaction of SNP-SNP in CHD risk was evaluated by multi-factor dimensionality reduction (MDR). Results: The results showed that BTNL2-rs35624343, -rs117896888, -rs41441651, -rs41417449, -rs28362680 and -rs2076523 were significantly associated with the CHD susceptibility. Especially for BTNL2-rs28362680, the allele A (OR = 0.68, p < 0.0001), genotype AA (OR = 0.40, p = 0.001) or GA (OR = 0.68, p < 0.0001) were associated with the reducing CHD risk. And -rs28362680 significantly reduced the CHD risk under all genetic models (dominant: OR = 0.64, p < 0.0001; recessive: OR = 0.47, p = 0.003; overdominant: OR = 0.73, p = 0.004; log-additive: OR = 0.66, p < 0.0001). And -rs28362680 was also closely associated with CHD risk reduction in all stratified analyses (age, gender, smoking, drinking, hypertension and diabetes). In addition, haplotype analysis showed that the "Crs117896888Crs41441651Trs41417449Ars28362680" (OR = 0.65, p < 0.0001) and "Grs117896888Trs41441651Crs41417449Ars28362680" (OR = 0.68, p = 0.013) may reduce CHD risk. Conclusion: Missense variants (rs35624343, rs117896888, rs41441651, rs41417449, rs28362680, rs2076523) may be protective factors for the CHD risk. In particular, there were sufficient evidences that BTNL2-rs28362680 can protective CHD risk.

16.
Phytochemistry ; 198: 113164, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35306002

RESUMO

Eight undescribed sesquiterpenes including seven guaianes and one pseudoguaiane which were named as wenyujinols A-H, along with ten known guaianes, were isolated from rhizomes of Curcuma wenyujin Y. H. Chen et C. Ling. The structures of wenyujinols A-H were elucidated by 1D and 2D nuclear magnetic resonance (NMR) data, high resolution mass spectrum (HRMS), electronic circular dichroism (ECD) spectra, and X-ray single crystallographic analysis. All of the isolated compounds were evaluated for antioxidant activity via activation of the Nrf2-ARE pathway in human embryonic kidney (HEK) 293 cells, for inhibitory effects on NO production in RAW 264.7 cells, and for cytotoxicity against three human cancer cell lines A549, HL60, and MCF7 in vitro. The results indicated that procurcumenol (50-200 µM) and 9-oxo-neoprocurcumenol (25-200 µM) exhibited antioxidant activity via activation of the Nrf2-ARE pathway in a dose-dependent manner.


Assuntos
Fator 2 Relacionado a NF-E2 , Sesquiterpenos , Antioxidantes/farmacologia , Curcuma/química , Curcuma/metabolismo , Células HEK293 , Humanos , Macrófagos , Estrutura Molecular , Fator 2 Relacionado a NF-E2/metabolismo , Óxido Nítrico , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos de Guaiano/química
17.
Arch Biochem Biophys ; 721: 109194, 2022 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-35337811

RESUMO

Androgen receptor (AR) is a promising therapeutic target for AR-positive triple-negative breast cancer (TNBC). However, clinical trials of AR inhibitors only reveal modest therapeutic efficacy for AR-positive TNBC, and drug resistance is also inevitable. To address these challenges, we herein report the use of an AR-targeting proteolysis targeting chimera (AR-PROTAC) to treat AR-positive TNBC. We demonstrated that AR-PROTAC potently degraded AR protein via the ubiquitin-proteasome pathway in AR-positive TNBC BT549 cells, with a half degradation concentration of ∼46.9 nM. By evaluating the therapeutic efficacies in vitro and in vivo, we validated that AR-PROTAC was superior to enzalutamide, an AR inhibitor. Specifically, AR-PROTAC at 100 nM reduced BT549 cell viability by up to ∼80%, and AR-PRTOAC at 10 mg/kg suppressed tumor growth by ∼60% when administrated intratumorally in subcutaneous BT549 tumor mice model. Overall, these results demonstrate for the first time that PROTAC holds promise to enhance the treatment of AR-positive TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Antagonistas de Receptores de Andrógenos/farmacologia , Antagonistas de Receptores de Andrógenos/uso terapêutico , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Proteólise , Receptores Androgênicos/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
18.
Anal Chem ; 94(12): 5069-5074, 2022 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-35286070

RESUMO

Mitochondria, as "cell energy stations", are involved in the regulation of various cell functions. Recent investigations revealed that mitochondrial dysfunction that can cause an intracellular viscosity mutation, a process that is associated with an increasing number of diseases that are not curable or manageable. However, conventional viscometers cannot be used to monitor the viscosity changes in living cells and in vivo. In order to cater to the complex biological environment, we present a chemical toolbox, MI-BP-CC, that employs N,N-diethyl and double bonds as sensitive sites for viscosity based on the TICT mechanism (twisted intramolecular charge transfer) to monitor the viscosity of living cells and fatter liver mice. MI-BP-CC features good mitochondrial targeting and a near-infrared emission. Surprisingly, in the presence of viscosity, the MI-BP-CC probe exhibited an ultrasensitive model for viscosity detection showing a red fluorescence signal from a silent "off" state to "on". More importantly, utilizing the satisfactory detection performance of MI-BP-CC, we have successfully visualized increased viscosity under the pathological models of Parkinson's (PD) and fatty liver mice. We anticipate that these findings will provide a convenient and efficient tool to understand physiological functions of viscosity in more biosystems.


Assuntos
Fígado Gorduroso , Corantes Fluorescentes , Animais , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/patologia , Corantes Fluorescentes/química , Células HeLa , Humanos , Camundongos , Mitocôndrias/química , Viscosidade
19.
Front Neurol ; 13: 798542, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35237229

RESUMO

BACKGROUND: There is no clear consensus on the optimal endovascular treatment strategy for patients with ischemic stroke caused by ICAS-related large vessel occlusion (LVO). SPACEMAN, a novel thrombectomy technique that entails passing an aspiration catheter over the stent retriever and then retaining the microwire for angioplasty, has not been described. The aim of this prospective study was to evaluate our initial application of SPACEMAN and compare this technique with the Solumbra technique. METHODS: Forty-four consecutive patients with acute ischemic stroke resulting from ICAS-related LVO were randomly divided into two groups: Solumbra group (n = 22) and SPACEMAN group (n = 22). Demographic and clinical data were prospectively collected. Modified Rankin Scale (mRS) score of ≤ 2 of anterior circulation and mRS score ≤ 3 of posterior circulation at 3 months post-discharge was regarded as good prognosis. RESULTS: The SPACEMAN group showed reduced mean time from femoral access to recanalization compared with the Solumbra group (39.55 ± 10.63 min vs. 50.73 ± 9.89 min, P = 0.001). The overall recanalization rate in the entire cohort was 93.18% (41/44). At 3-month follow-up, the overall good prognosis rate was 47.73%; 13 patients (59.09%) in the SPACEMAN group and 8 (36.36%) in the Solumbra group showed good prognosis. One patient in the SPACEMAN group (4.55%) and two patients in the Solumbra group (9.09%) developed symptomatic intracranial hemorrhage. The overall mortality rate was 4.55% (2/44). CONCLUSIONS: This study suggests that SPACEMAN exhibits a shorter operation revascularization time than the standard thrombectomy. Complications and prognosis were comparable between the two groups. The safety and efficacy of this novel technique need to be studied in larger patient series.

20.
Fitoterapia ; 158: 105167, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35227788

RESUMO

Nine new sesquiterpenes wenyujinones A-I (1-9), along with ten known ones (10-19), were isolated from the rhizomes of Curcuma wenyujin Y. H. Chen et C. Ling (C. wenyujin). The chemical structures of compounds 1-9 were elucidated by NMR spectroscopic and mass spectrometric data, electronic circular dichroism (ECD) spectra analysis. Furthermore, all compounds were evaluated for the protective effects against hydrogen peroxide (H2O2)-induced injury in human hepatic L02 cells, for the inhibitory effects on nitric oxide (NO) production in RAW 264.7 cells, and for their cytotoxicity against three human cancer cell lines A549, HL60, and MCF7 in vitro. As a result, compounds 2, 4, 14 markedly weakened the oxidative damage induced by H2O2 in L02 cells via strengthening the cell viability.


Assuntos
Curcuma , Sesquiterpenos , Curcuma/química , Humanos , Peróxido de Hidrogênio/análise , Estrutura Molecular , Rizoma/química , Sesquiterpenos/química
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