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1.
J Cell Mol Med ; 28(2): e18053, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38014923

RESUMEN

Immune disorders caused by sepsis have recently drawn much attention. We sought to dynamically monitor the expression of small extracellular vesicle (sEV) miRNAs in peripheral blood during sepsis to explore these miRNAs as potential biomarkers for monitoring immune function in sepsis patients. This study included patients with sepsis. Blood samples were obtained from 10 patients on the first through 10th days, the 12th day and the 14th day since sepsis onset, resulting in 120 collected samples. Serum sEVs were extracted from peripheral venous blood, and levels of MIR497HG, miR-195, miR-497, and PD-L1 in serum sEVs were detected by qPCR, and clinical information was recorded. Our study revealed that the levels of MIR497HG, miR-195, miR-497 and PD-L1 in serum sEVs showed periodic changes; the time from peak to trough was approximately 4-5 days. The levels of sEV MIR497HG and miR-195 had a positive linear relationship with SOFA score (r values were -0.181 and -0.189; p values were 0.048 and 0.039, respectively). The recorded quantities of sEV MIR497HG, miR-195 and PD-L1 showed a substantial correlation with ARDS. ROC curve analysis revealed that sEV MIR497HG, miR-195 and miR-497 could predict the 28-day mortality of sepsis patients with an AUC of 0.66, 0.68 and 0.72, respectively. Levels of sEVs MIR497HG, miR-195, miR-497 and PD-L1 showed periodic changes with the immune status of sepsis, which provides a new exploration direction for immune function biomarkers and immunotherapy timing in sepsis patients.


Asunto(s)
Vesículas Extracelulares , MicroARNs , Sepsis , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Antígeno B7-H1/metabolismo , Sepsis/metabolismo , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Biomarcadores/metabolismo
2.
Hum Mol Genet ; 31(23): 4094-4106, 2022 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-35848890

RESUMEN

High-throughput circular RNA (circRNA) sequencing identified circRNA_001678 (circ_001678) as an upregulated circRNA in non-small cell lung cancer (NSCLC) tissues. Hence, the current study sought to investigate the function and the underlying mechanism of circRNA_001678 in immune escape of NSCLC. Briefly, commercially purchased NSCLC cell lines were adopted for in vitro experiment to evaluate the effects of circ_001678 over-expression or knockdown on cell biological functions, including proliferation, migration and invasive abilities. In addition, the effects of circ_001678 on the in vivo tumorigenicity ability were evaluated for verification. Accordingly, we uncovered that circ_001678 over-expression augmented NSCLC progression in vitro and enhanced tumorigenicity ability in vivo. The interaction between circ_001678 and miR-326 predicted online was verified by means of luciferase and RNA pull-down assays. Furthermore, circ_001678 could sponge miR-326 to up-regulate ZEB1. On the other hand, the tumor-promoting effects of circ_001678 could be inhibited by anti-PD-L1/PD-1 treatment. Mechanistically, circ_001678 led to the activation of the PD-1/PD-L1 pathway to promote CD8+ T cell apoptosis, thereby inducing NSCLC cell immune escape via regulation of the miR-326/ZEB1 axis. To conclude, our findings revealed that circ_001678 sponges miR-326 to up-regulate ZEB1 expression and induce the PD-1/PD-L1 pathway-dependent immune escape, thereby promoting the malignant progression of NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptor de Muerte Celular Programada 1/genética , ARN Circular/genética , Neoplasias Pulmonares/genética , MicroARNs/genética , Proliferación Celular/genética , Línea Celular Tumoral , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética
3.
J Biochem Mol Toxicol ; 38(7): e23761, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38952040

RESUMEN

Non-small cell cancer (NSCLC) is the most common cancer in the world, but its effective therapeutic methods are limited. Tilianin and sufentanil alleviate various human tumors. This research aimed to clarify the functions and mechanisms of Tilianin and sufentanil in NSCLC. The functions of Tilianin and sufentanil on NSCLC cell viability, apoptosis, mitochondrial dysfunction, and immunity in vitro were examined using Cell Counting Kit-8 assay, flow cytometry, reactive oxygen species level analysis, CD8+ T cell percentage analysis, Western blot, and enzyme-linked immunosorbent assay, respectively. The molecular mechanism regulated by Tilianin and sufentanil in NSCLC was assessed using Western blot, and immunofluorescence assays. Meanwhile, the roles of Tilianin and sufentanil in NSCLC tumor growth, apoptosis, and immunity in vivo were determined by establishing a tumor xenograft mouse model, immunohistochemistry, and Western blot assays. When sufentanil concentration was proximity 2 nM, the inhibition rate of NSCLC cell viability was 50%. The IC50 for A549 cells was 2.36 nM, and the IC50 for H1299 cells was 2.18 nM. The IC50 of Tilianin for A549 cells was 38.7 µM, and the IC50 of Tilianin for H1299 cells was 44.6 µM. Functionally, 0.5 nM sufentanil and 10 µM Tilianin reduced NSCLC cell (A549 and H1299) viability in a dose-dependent manner. Also, 0.5 nM sufentanil and 10 µM Tilianin enhanced NSCLC cell apoptosis, yet this impact was strengthened after a combination of Tilianin and Sufentanil. Furthermore, 0.5 nM sufentanil and 10 µM Tilianin repressed NSCLC cell mitochondrial dysfunction and immunity, and these impacts were enhanced after a combination of Tilianin and Sufentanil. Mechanistically, 0.5 nM sufentanil and 10 µM Tilianin repressed the NF-κB pathway in NSCLC cells, while this repression was strengthened after a combination of Tilianin and Sufentanil. In vivo experimental data further clarified that 1 µg/kg sufentanil and 10 mg/kg Tilianin reduced NSCLC growth, immunity, and NF-κB pathway-related protein levels, yet these trends were enhanced after a combination of Tilianin and Sufentanil. Tilianin strengthened the antitumor effect of sufentanil in NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Sufentanilo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Humanos , Sufentanilo/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Animales , Ratones , Apoptosis/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Células A549 , Ratones Desnudos , Sinergismo Farmacológico , Línea Celular Tumoral , Ratones Endogámicos BALB C , Antineoplásicos/farmacología , Sulfatos de Condroitina/farmacología , Venenos de Anfibios
4.
J Nat Prod ; 87(2): 228-237, 2024 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-38266493

RESUMEN

As a model liverwort, Marchantia polymorpha contains various flavone glucuronides with cardiovascular-promoting effects and anti-inflammatory properties. However, the related glucuronosyltransferases have not yet been reported. In this study, two bifunctional UDP-glucuronic acid/UDP-glucose:flavonoid glucuronosyltransferases/glucosyltransferases, MpUGT742A1 and MpUGT736B1, were identified from M. polymorpha. Extensive enzymatic assays found that MpUGT742A1 and MpUGT736B1 exhibited efficient glucuronidation activity for flavones, flavonols, and flavanones and showed promiscuous regioselectivity at positions 3, 6, 7, 3', and 4'. These enzymes catalyzed the production of a variety of flavonoid glucuronides with medicinal value, including apigenin-7-O-glucuronide and scutellarein-7-O-glucuronide. With the use of MpUGT736B1, apigenin-4'-O-glucuronide and apigenin-7,4'-di-O-glucuronide were prepared by scaled-up enzymatic catalysis and structurally identified by NMR spectroscopy. MpUGT742A1 also displayed glucosyltransferase activity on the 7-OH position of the flavanones using UDP-glucose as the sugar donor. Furthermore, we constructed four recombinant strains by combining the pathway for increasing the UDP-glucuronic acid supply with the two novel UGTs MpUGT742A1 and MpUGT736B1. When apigenin was used as a substrate, the extracellular apigenin-4'-O-glucuronide and apigenin-7,4'-di-O-glucuronide production obtained from the Escherichia coli strain BB2 reached 598 and 81 mg/L, respectively. Our study provides new candidate genes and strategies for the biosynthesis of flavonoid glucuronides.


Asunto(s)
Flavanonas , Marchantia , Flavonoides/química , Apigenina , Glucurónidos/metabolismo , Marchantia/metabolismo , Glucuronosiltransferasa/química , Glucuronosiltransferasa/metabolismo , Escherichia coli/metabolismo , Glucosa , Ácido Glucurónico , Uridina Difosfato
5.
Environ Res ; 244: 117865, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38103776

RESUMEN

Rhizosphere soil fungal and enzyme activities affect the nutrient cycling of terrestrial ecosystems, and rhizosphere fungi are also important participants in the ecological process of vegetation succession, responding to changes in plant communities. Stipa is an excellent forage grass with important ecological and economic value, and has the spatial distribution pattern of floristic geographical substitution. In order to systematically investigate the synergistic response strategies of fungal communities and enzyme activities in the rhizosphere under the vegetation succession. Here we explored the turnover and assembly mechanisms of Stipa rhizosphere fungal communities and the spatial variation of metabolic activity under the succession of seven Stipa communities in northern China grassland under large scale gradients. The results indicated that the composition, abundance and diversity of fungal communities and microbial enzyme activities in rhizosphere soil differed among different Stipa species and were strikingly varied along the Stipa community changes over the geographic gradient. As the geographical distribution of Stipa community changed from east to west in grassland transect, Mortierellomycetes tended to be gradually replaced by Dothideomycetes. The null models showed that the rhizosphere fungal communities were governed primarily by the dispersal limitation of stochastic assembly processes, which showed decreased relative importance from S. grandis to S. gobica. Moreover, the MAT and MAP were the most important factors influencing the changes in the fungal community (richness, ß-diversity and composition) and fungal community assembly, while SC and NP also mediated fungal community assembly processes. These findings deepen our understanding of the responses of the microbial functions and fungal community assembly processes in the rhizosphere to vegetation succession.


Asunto(s)
Micobioma , Rizosfera , Humanos , Suelo , Ecosistema , Pradera , Microbiología del Suelo , Poaceae/microbiología , China
6.
World J Surg ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38955808

RESUMEN

BACKGROUND: The superiority between remimazolam and propofol for anesthesia is controversial in elderly patients (≥60 years). This meta-analysis aimed to systematically compare anesthetic effect and safety profile between remimazolam and propofol in elderly patients under any surgery. METHODS: Cochrane Library, Web of Science, and PubMed were searched until December 25, 2023 for relevant randomized controlled trials. RESULTS: Ten studies with 806 patients receiving remimazolam (experimental group) and 813 patients receiving propofol (control group) were included. Time to loss of consciousness [standard mean difference (SMD) (95% confidence interval (CI): 1.347 (-0.362, 3.055), p = 0.122] and recovery time [SMD (95% CI): -0.022 (-0.300, 0.257), p = 0.879] were similar between experimental and control groups. Mean arterial pressure at baseline minus 1 min after induction [SMD (95% CI): -1.800 (-3.250, -0.349), p = 0.015], heart rate at baseline minus 1 min after induction [SMD (95% CI): -1.041 (-1.537, -0.545), p < 0.001], incidences of hypoxemia [relative risk (RR) (95% CI): 0.247 (0.138, 0.444), p < 0.001], respiratory depression [RR (95% CI): 0.458 (0.300, 0.700), p < 0.001], bradycardia [RR (95% CI): 0.409 (0.176, 0.954), p = 0.043], hypotension [RR (95% CI): 0.415 (0.241, 0.714), p = 0.007], and injection pain [RR (95% CI): 0.172 (0.113, 0.263), p < 0.001] were lower in the experimental group compared to the control group. Postoperative nausea and vomiting was not different between groups [RR (95% CI): 1.194 (0.829, 1.718), p = 0.341]. Moreover, this meta-analysis displayed a low risk of bias, minimal publication bias, and good robustness. CONCLUSION: Remimazolam shows comparative anesthetic effect and better safety profile than propofol in elderly patients under any surgery.

7.
J Appl Toxicol ; 44(8): 1198-1213, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38639436

RESUMEN

Intracerebral hemorrhage (ICH), for which there are currently no effective preventive or treatment methods, has a very high fatality rate. Statins, such as atorvastatin (ATV), are the first-line drugs for regulating blood lipids and treating hyperlipidemia-related cardiovascular diseases. However, ATV-associated ICH has been reported, although its incidence is rare. In this study, we aimed to investigate the protective action and mechanisms of berberine (BBR) against ATV-induced brain hemorrhage. We established an ICH model in zebrafish induced by ATV (2 µM) and demonstrated the effects of BBR (10, 50, and 100 µM) on ICH via protecting the vascular network using hemocyte staining and three transgenic zebrafish. BBR was found to reduce brain inflammation and locomotion injury in ICH-zebrafish. Mechanism research showed that ATV increased the levels of VE-cadherin and occludin proteins but disturbed their localization at the cell membrane by abnormal phosphorylation, which decreased the number of intercellular junctions between vascular endothelial cells (VECs), disrupting the integrity of vascular walls. BBR reversed the effects of ATV by promoting autophagic degradation of phosphorylated VE-cadherin and occludin in ATV-induced VECs examined by co-immunoprecipitation (co-IP). These findings provide crucial insights into understanding the BBR mechanisms involved in the maintenance of vascular integrity and in mitigating adverse reactions to ATV.


Asunto(s)
Atorvastatina , Berberina , Hemorragia Cerebral , Pez Cebra , Animales , Atorvastatina/farmacología , Hemorragia Cerebral/inducido químicamente , Berberina/farmacología , Animales Modificados Genéticamente , Modelos Animales de Enfermedad , Células Endoteliales/efectos de los fármacos
8.
Artículo en Inglés | MEDLINE | ID: mdl-38960394

RESUMEN

INTRODUCTION: Antithrombin (AT) deficiency is a rare but highly thrombogenic inherited thrombophilia. Its association with adverse pregnancy outcomes (APO) is undefined. There is limited guidance on managing AT deficiency in pregnancy. Some significant issues remain controversial, including risk assessment for prophylactic anticoagulation, anticoagulant therapy, and monitoring. Our goal was to examine if the antepartum management of patients with AT deficiency affected their pregnancy outcomes. MATERIALS AND METHODS: This retrospective, single-center observational study included pregnant women with inherited AT deficiency in Peking Union Medical College Hospital between 2013 and 2024. RESULTS: Seventeen pregnancies in 6 women with AT deficiency were identified. A total of 7 pregnancies received adjusted-dose low-molecular-weight heparin (LMWH) and were monitored by anti-Xa level, AT activity, and D-dimer. There were 5 live births (all received LMWH), 7 second-trimester abortions (1 received LMWH), and 5 early pregnancy losses (1 received LMWH). There were 5 abruptio placentae events (3 received LMWH) and 7 thrombotic events (2 received LMWH). CONCLUSIONS: AT deficiency is at least an important partial factor contributing to APO. It is suggested to make a full assessment of AT patients both for venous thrombus embolism and APO risk. We observed a high prevalence of heparin resistance and a positive correlation between adequate anticoagulation and pregnancy outcome based on tight monitoring with anti-Xa level and timely adjustment of the LMWH dosage.

9.
Sensors (Basel) ; 24(3)2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38339504

RESUMEN

ß-Ga2O3 photodetectors have the advantages of low dark current and strong radiation resistance in UV detection. However, the limited photocurrent has restricted their applications. Herein, MSM UV photodetectors based on (InxGa1-x)2O3 (x = 0, 0.1, 0.2, 0.3) by a sol-gel method were fabricated and studied. The doping of indium ions in Ga2O3 leads to lattice distortion and promotes the formation of oxygen vacancies. The oxygen vacancies in (InxGa1-x)2O3 can be modulated by various proportions of indium, and the increased oxygen vacancies contribute to the enhancement of electron concentration. The results show that the amorphous In0.4Ga1.6O3 photodetector exhibited improved performances, including a high light-to-dark current ratio (2.8 × 103) and high responsivity (739.2 A/W). This work provides a promising semiconductor material In0.4Ga1.6O3 for high-performance MSM UV photodetectors.

10.
J Am Chem Soc ; 145(11): 6057-6066, 2023 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-36888741

RESUMEN

The development of efficient photocatalysts for N2 fixation to produce NH3 under ambient conditions remains a great challenge. Since covalent organic frameworks (COFs) possess predesignable chemical structures, good crystallinity, and high porosity, it is highly significant to explore their potential for photocatalytic nitrogen conversion. Herein, we report a series of isostructural porphyrin-based COFs loaded with Au single atoms (COFX-Au, X = 1-5) for photocatalytic N2 fixation. The porphyrin building blocks act as the docking sites to immobilize Au single atoms as well as light-harvesting antennae. The microenvironment of the Au catalytic center is precisely tuned by controlling the functional groups at the proximal and distal positions of porphyrin units. As a result, COF1-Au decorated with strong electron-withdrawing groups exhibits a high activity toward NH3 production with rates of 333.0 ± 22.4 µmol g-1 h-1 and 37.0 ± 2.5 mmol gAu-1 h-1, which are 2.8- and 171-fold higher than that of COF4-Au decorated with electron-donating functional groups and a porphyrin-Au molecular catalyst, respectively. The NH3 production rates could be further increased to 427.9 ± 18.7 µmol g-1 h-1 and 61.1 ± 2.7 mmol gAu-1 h-1 under the catalysis of COF5-Au featuring two different kinds of strong electron-withdrawing groups. The structure-activity relationship analysis reveals that the introduction of electron-withdrawing groups facilitates the separation and transportation of photogenerated electrons within the entire framework. This work manifests that the structures and optoelectronic properties of COF-based photocatalysts can be finely tuned through a rational predesign at the molecular level, thus leading to superior NH3 evolution.

11.
J Am Chem Soc ; 145(50): 27531-27538, 2023 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-38054906

RESUMEN

Single-atom catalysts exhibit promising electrocatalytic activity, a trait that can be further enhanced through the introduction of heteroatom doping within the carbon skeleton. Nonetheless, the intricate relationship between the doping positions and activity remains incompletely elucidated. This contribution sheds light on an inductive effect of single-atom sites, showcasing that the activity of the oxygen reduction reaction (ORR) can be augmented by reducing the spatial gap between the doped heteroatom and the single-atom sites. Drawing inspiration from this inductive effect, we propose a synthesis strategy involving ligand modification aimed at precisely adjusting the distance between dopants and single-atom sites. This precise synthesis leads to optimized electrocatalytic activity for the ORR. The resultant electrocatalyst, characterized by Fe-N3P1 single-atom sites, demonstrates remarkable ORR activity, thus exhibiting great potential in zinc-air batteries and fuel cells.

12.
New Phytol ; 237(2): 515-531, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36062450

RESUMEN

Unlike bibenzyls derived from the vascular plants, lunularic acid (LA), a key precursor for macrocyclic bisbibenzyl synthesis in nonvascular liverworts, exhibits the absence of one hydroxy group within the A ring. It was hypothesized that both polyketide reductase (PKR) and stilbenecarboxylate synthase 1 (STCS1) were involved in the LA biosynthesis, but the underlined mechanisms have not been clarified. This study used bioinformatics analysis with molecular, biochemical and physiological approaches to characterize STCS1s and PKRs involved in the biosynthesis of LA. The results indicated that MpSTCS1s from Marchantia polymorpha catalyzed both C2→C7 aldol-type and C6→C1 Claisen-type cyclization using dihydro-p-coumaroyl-coenzyme A (CoA) and malonyl-CoA as substrates to yield a C6-C2-C6 skeleton of dihydro-resveratrol following decarboxylation and the C6-C3-C6 type of phloretin in vitro. The protein-protein interaction of PKRs with STCS1 (PPI-PS) was revealed and proved essential for LA accumulation when transiently co-expressed in Nicotiana benthamiana. Moreover, replacement of the active domain of STCS1 with an 18-amino-acid fragment from the chalcone synthase led to the PPI-PS greatly decreasing and diminishing the formation of LA. The replacement also increased the chalcone formation in STCS1s. Our results highlight a previously unrecognized PPI in planta that is indispensable for the formation of LA.


Asunto(s)
Marchantia , Salicilatos , Coenzima A/química
13.
Clin Exp Rheumatol ; 41(7): 1480-1490, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36622337

RESUMEN

OBJECTIVES: To explore the potential biomarkers and mechanisms in obstetric antiphospholipid syndrome (OAPS) patients by placental proteomics. METHODS: Among 212 follow-up pregnancy patients based on the Chinese Rheumatism Data Center database (CRDC), we continuously recruited 30 pregnancy patients at the late stage of pregnancy for proteomics study. Fresh placental tissues were collected and 4D label-free technologies were used to analyse the placental proteome in patients. Bioinformatic analysis was applied to identify differentially expressed proteins (DEPs) and crucial pathways. Placental tissues were also stained with haematoxylin and eosin (H & E) for histological analysis. RESULTS: We collected 7 OAPS patients (33.85±1.57 years), 4 SAPS patients (34.25 ± 3.86 years), 8 SLE patients (30.38±2.56 years), and 11 healthy controls (31.45±3.01 years). All patients in the SAPS and OAPS group had adverse pregnancy history. A total of 7040 proteins containing at least one unique peptide were identified. There were 214 DEPs between the healthy group and the OAPS group, of which 82 proteins were upregulated and 132 proteins were downregulated in the OAPS group based on fold change ≥1.5 and p-values ≤0.05. We found that the complement and coagulation pathway played a significant role in OAPS patients. Several key proteins (C1Q, C4b, SERPINA1, plasminogen) highly expressed in placental tissues, that may serve as biomarkers for OAPS patients. CONCLUSIONS: The complement and coagulation pathway and related DEPs (SERPINA1 and plasminogen) were of crucial importance in OAPS patients.


Asunto(s)
Síndrome Antifosfolípido , Complicaciones del Embarazo , Humanos , Embarazo , Femenino , Síndrome Antifosfolípido/diagnóstico , Plasminógeno , Placenta , Biomarcadores , alfa 1-Antitripsina
14.
Bioorg Chem ; 134: 106459, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36924653

RESUMEN

Both estrogen receptor α (ERα) and histone deacetylases (HDACs) are valid therapeutic targets for anticancer drug development. Combination therapies using diverse ERα antagonists or degraders and HDAC inhibitors have been proven effective in endocrine-resistant ER + breast cancers based on the crosstalk between ERα and HDAC pathway. In this study, we reported the optimization of a series of methoxyphenyl- or pyridinyl- substituted tetrahydroisoquinoline-hydroxamates, which were optimized from 31, a dual ERα degrader/HDAC inhibitor previously reported by our group. Most of the synthesized compounds displayed potent ERα degradation efficacy and antiproliferative activity. Among them, A04 demonstrated the best anti-proliferation activity (MCF-7 IC50 = 1.96 µM) and HDAC6 inhibitory activity (HDAC6 IC50 = 25.96 nM), which is slightly more potent than the lead compound 31 (MCF-7 IC50 = 4.38 µM, HDAC6 IC50 = 63.03 nM). In addition, compound A04 exerted ERα-independent HDAC6-inhibiting effect without agonistic activity in endometrial cells. These results demonstrated that A04 is a novel and promising dual ERα degrader/HDAC inhibitor worthy of further development.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Tetrahidroisoquinolinas , Humanos , Femenino , Inhibidores de Histona Desacetilasas/química , Receptor alfa de Estrógeno/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Histona Desacetilasas/metabolismo , Ácidos Hidroxámicos/farmacología , Tetrahidroisoquinolinas/farmacología , Proliferación Celular , Antineoplásicos/química , Relación Estructura-Actividad , Línea Celular Tumoral
15.
Plant Cell Rep ; 42(12): 1951-1965, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37805949

RESUMEN

KEY MESSAGE: VAMP726/VAMP725 and SYP131 can form a part of a SNARE complex to mediate vesicle secretion at the pollen tube apex. Secretory vesicle fusion with the plasma membrane of the pollen tube tip is a key step in pollen tube growth. Membrane fusion was mediated by SNAREs. However, little is known about the composition and function of the SNARE complex during pollen tube tip growth. In this study, we constructed a double mutant vamp725 vamp726 via CRISPR‒Cas9. Fluorescence labeling combined with microscopic observation, luciferase complementation imaging, co-immunoprecipitation and GST pull-down were applied in the study. We show that double mutation of the R-SNAREs VAMP726 and VAMP725 significantly inhibits pollen tube growth in Arabidopsis and slows vesicle exocytosis at the apex of the pollen tube. GFP-VAMP726 and VAMP725-GFP localize mainly to secretory vesicles and the plasma membrane at the apex of the pollen tube. In addition, fluorescence recovery after photobleaching (FRAP) experiments showed that mCherry-VAMP726 colocalizes with Qa-SNARE SYP131 in the central region of the pollen tube apical plasma membrane. Furthermore, we found that VAMP726 and VAMP725 can interact with the SYP131. Based on these results, we suggest that VAMP726/VAMP725 and SYP131 can form a part of a SNARE complex to mediate vesicle secretion at the pollen tube apex, and vesicle secretion may mainly occur at the central region of the pollen tube apical plasma membrane.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Tubo Polínico/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Membrana Celular/metabolismo , Proteínas SNARE/genética , Proteínas SNARE/metabolismo
16.
BMC Geriatr ; 23(1): 284, 2023 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-37170210

RESUMEN

BACKGROUND: There is well-established evidence to understand the characteristics of falls among the older patients with hip fracture in many countries, but very little knowledge existed in China. This study described the characteristics of falls in older patients with hip fractures from six Chinese hospitals. METHODS: This cross-sectional study is a post-hoc descriptive analysis of a recently completed trial. Eligible patients were aged 65 years and older, with confirmed hip fractures due to falls, and were admitted to the hospital within 21 days of the fracture. All patients were consecutively enrolled and screened within one year (November 15, 2018, to November 14, 2019). The collected data included patient demographics and fall-related information. RESULTS: A total of 1,892 patients' fall-related information were described. Most patients with hip fractures caused by falls were in the oldest old age group (60.4% in age group ≥ 80), with an overall average age of 80.7 (7.6) years. There were more females (n = 1,325, 70.0%) than males (n = 567, 30.0%). The majority lived in urban (n = 1,409, 74.5%). Most falls (n = 1,237, 67.3%) occurred during the daytime (6:01-18:00). There were 1,451 patients had their falls occurring at home (76.7%). Lost balance (n = 1,031, 54.5%) was reported as the primary reason to cause falls. The most common activity during a fall was walking (n = 1,079, 57.0%). CONCLUSIONS: Although the incidence of fall-related hip fractures in China is unclear, preventing falls and fall-related hip fractures in older people remains an urgent health concern as the ageing society increases. Studies with larger sample size and diverse population are needed to robustly understand this growing epidemic.


Asunto(s)
Fracturas de Cadera , Masculino , Anciano de 80 o más Años , Femenino , Humanos , Anciano , Estudios Transversales , Fracturas de Cadera/epidemiología , Fracturas de Cadera/prevención & control , Caminata , Hospitales , Factores de Riesgo
17.
BMC Med Inform Decis Mak ; 23(1): 157, 2023 08 11.
Artículo en Inglés | MEDLINE | ID: mdl-37568134

RESUMEN

BACKGROUND: Artificial intelligence (AI) tools are more effective if accepted by clinicians. We developed an AI-based clinical decision support system (CDSS) to facilitate vancomycin dosing. This qualitative study assesses clinicians' perceptions regarding CDSS implementation. METHODS: Thirteen semi-structured interviews were conducted with critical care pharmacists, at Mayo Clinic (Rochester, MN), from March through April 2020. Eight clinical cases were discussed with each pharmacist (N = 104). Following initial responses, we revealed the CDSS recommendations to assess participants' reactions and feedback. Interviews were audio-recorded, transcribed, and summarized. RESULTS: The participants reported considerable time and effort invested daily in individualizing vancomycin therapy for hospitalized patients. Most pharmacists agreed that such a CDSS could favorably affect (N = 8, 62%) or enhance (9, 69%) their ability to make vancomycin dosing decisions. In case-based evaluations, pharmacists' empiric doses differed from the CDSS recommendation in most cases (88/104, 85%). Following revealing the CDSS recommendations, we noted 78% (69/88) discrepant doses. In discrepant cases, pharmacists indicated they would not alter their recommendations. The reasons for declining the CDSS recommendation were general distrust of CDSS, lack of dynamic evaluation and in-depth analysis, inability to integrate all clinical data, and lack of a risk index. CONCLUSION: While pharmacists acknowledged enthusiasm about the advantages of AI-based models to improve drug dosing, they were reluctant to integrate the tool into clinical practice. Additional research is necessary to determine the optimal approach to implementing CDSS at the point of care acceptable to clinicians and effective at improving patient outcomes.


Asunto(s)
Sistemas de Apoyo a Decisiones Clínicas , Vancomicina , Humanos , Inteligencia Artificial , Farmacéuticos
18.
Arch Gynecol Obstet ; 307(1): 263-274, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35474494

RESUMEN

PURPOSE: To analyze the clinical characteristics of abdominal pregnancy, and to explore the diagnosis and prognosis of different treatment methods. METHODS: The cases of patients with abdominal pregnancy admitted to Peking Union Medical College Hospital between January 1, 1989 and January 1, 2021, were analyzed retrospectively. RESULTS: The median age of 17 patients was 34 years (22-42 years); the median gestational duration was 57 days (from 41 days to 32 weeks). Among all 17 patients, 15 (88.24%) presented with abdominal pain. The implantation sites of the gestational sac included the bladder peritoneal reflection, anterior wall of the rectum, omentum, serous membrane of the uterus, and inside or on the surface of uterosacral ligament. In all, only 29.41% cases (5/17) were diagnosed before surgery. All 17 patients were treated via surgery. Further, 58.82% (10/17) patients recovered without complications, 29.41% (5/17) developed fever, 5.88% (1/17) underwent reoperation because of intra-abdominal bleeding, and 5.88% (1/17) developed double lower limb venous thrombosis. All 17 patients survived. CONCLUSION: The preoperative diagnosis rate of abdominal pregnancy is low. Planting sites in the pelvic peritoneum and pelvic organs are more common than the others. Laparoscopic surgery in the first trimester of pregnancy can achieve better therapeutic effects. However, the blood supply of the placenta should be fully evaluated before surgery. When it is expected that attempts to remove the placenta will cause fatal bleeding, the placenta can be left in place, but long-term close follow-up should be paid attention to.


Asunto(s)
Embarazo Abdominal , Embarazo , Femenino , Humanos , Adulto , Embarazo Abdominal/diagnóstico , Embarazo Abdominal/cirugía , Estudios Retrospectivos , Placenta , Primer Trimestre del Embarazo , Útero
19.
BMC Med Educ ; 23(1): 541, 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37525126

RESUMEN

BACKGROUND: Digital health is important for sustainable health systems and universal health coverage. Since the outbreak of COVID-19, many countries, including China, have promoted the introduction of digital health in their medical services. Developing the next generation of physicians with digital health knowledge and skills is a prerequisite for maximizing the potential of digital health. OBJECTIVE: We aimed to understand the perception of digital health among Chinese medical students, the current implementation of digital health education in China, and the urgent need of medical students. METHODS: Our cross-sectional survey was conducted online and anonymously among current medical students in China. We used descriptive statistical analysis to examine participant demographic characteristics and the demand for digital health education. Additional analysis was conducted by grouping responses by current participation in a digital health course. RESULTS: A total of 2122 valid responses were received from 467 medical schools. Most medical students had positive expectations that digital health will change the future of medicine. Compared with wearable devices (85.53%), telemedicine (84.16%), and medical big data (86.38%), fewer respondents believed in the benefits of clinical decision support systems (CDSS) (63.81%). Most respondents said they urgently needed digital health knowledge and skills, and the teaching method of practical training and internship (78.02%) was more popular than the traditional lecture (10.54%). However, only 41.45% wanted to learn about the ethical and legal issues surrounding digital health. CONCLUSIONS: Our study shows that the current needs of Chinese medical students for digital health education remain unmet. A national initiative on digital health education, is necessary and attention should be paid to digital health equity and education globally, focusing on CDSS and artificial intelligence. Ethics knowledge must also be included in medical curriculum. Students as Partners (SAP) is a promising approach for designing digital health courses.


Asunto(s)
COVID-19 , Estudiantes de Medicina , Humanos , Estudios Transversales , Inteligencia Artificial , COVID-19/epidemiología , Curriculum , Educación en Salud
20.
Telemed J E Health ; 29(5): 646-656, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36251955

RESUMEN

Background: While the use of telemedicine had been expanding before the initial outbreak of COVID-19, the pandemic has dramatically accelerated its implementation and expanded its usage in many hospitals. Tele-intensive care unit (ICU) is a specialized type of telemedicine that adapts available technologies to the unique needs of critically ill patients. We published an editorial in 2020 describing our initial experiences of Tele-ICU application in Shandong Province. Here, we update our insights gained over the past 2 years, and we provide a systematic review of the literature to compare our perspectives with those from other institutions. Methods: We performed a systematic literature review of publications describing the use of telemedicine in an ICU setting during COVID-19. The PubMed database was searched for studies published after January 1, 2020, which offered detailed descriptions of tele-ICU usage. Extracted data included details regarding tele-ICU technologies, descriptions of the institution, usage cases, assessments of tele-ICU effectiveness, and site-reported opinions (e.g., advantages, disadvantages). Results: We screened 162 studies resulting from the PubMed literature search, along with one expert recommendation. Of the 112 full-text articles retrieved, 11 were selected for inclusion in this qualitative summary. All were retrospective descriptions of tele-ICU experiences at a single site. Some pairs of included articles reported results from the same institution, with seven unique sites being described. Three sites employed centralized models of tele-ICU, while four allowed staff to participate from distant locations. Five sites collected user-reported feedback regarding tele-ICU. While the advantages and disadvantages described rarely overlapped directly between sites, many reported positive opinions of tele-ICU use overall. Conclusions: The potential applications of tele-ICU technologies vary widely, making them highly adaptable to the needs of individual institutions. Tele-ICU has proven invaluable to some hospitals during COVID-19 due to its effectiveness at aiding patient care while mitigating risk to health care workers.


Asunto(s)
COVID-19 , Telemedicina , Humanos , Cuidados Críticos/métodos , Pandemias , Estudios Retrospectivos , COVID-19/epidemiología , Unidades de Cuidados Intensivos
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