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1.
Anal Chem ; 96(19): 7487-7496, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38695134

RESUMEN

Cinchona alkaloid derivatives as Brønsted base catalysts have attracted considerable attention in the field of asymmetric catalysis. However, their potential application as chiral solvating agents has not been described. In this research, we investigated the use of the Cinchona alkaloid dimer, namely, (DHQ)2PHAL, as a chiral solvating agent for discerning various mandelic acid derivatives through 1H NMR spectroscopy. The addition of catalytic amounts of DMAP facilitated this process. Our experimental results demonstrate that dimeric (DHQ)2PHAL exhibits remarkable chiral discrimination properties regarding the diagnostic split protons of 1H NMR signals (including 24 examples, up to 0.321 ppm). Furthermore, it serves as an excellent chiral discriminating agent and provides good resolution for racemic chiral phosphoric acid as determined by 31P NMR spectroscopy. The quality of enantiodifferentiation has also been evaluated by means of the parameter "resolution (Rs)". Significantly, this class of CSAs based on (alkaloid)2linker systems with an azaaromatic linker can be directly employed, which is commercially available in an enantiopure form at very low cost and exhibits promising potential in determining the enantiopurity of α-hydroxy acids by chemoselective and biocatalytic reactions.

2.
Chemphyschem ; 25(5): e202300642, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38165629

RESUMEN

The vertical detachment energy (VDE) is a vital factor for predicting the stability of anions that have important applications in the atom, molecule and cluster science. Due to the synthetic or characterization difficulty of anions, accurate and efficient predictions of VDE independent of laboratory data have always been an appealing task to remedy the experimental deficiencies. Unfortunately, the generally adopted CCSD(T) and electron propagator theory (EPT) methods have respectively been proven to be reliable but very cost-expensive, and cost-effective but sometimes problematic when Koopman's theorem is invalid. Here, we for the first time introduced and benchmarked a series of model chemistry composite methods (e. g., CBS-QB3, G4 and W1BD) on calculating VDE for 57 molecular anions. Notably, CBS-QB3 exceeds the accuracy of CCSD(T) while approaching the economy of EPT. Therefore, we highly recommend the composite method CBS-QB3 to compute VDEs for molecular anions in the attractive "killing two birds with one stone" manner.

3.
Phys Chem Chem Phys ; 26(2): 1077-1085, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38098362

RESUMEN

A Cu-Fe bimetallic hydrogel (2-QF-CuFe-G) was constructed through a simple method. The 2-QF-CuFe-G metallohydrogel possesses excellent peroxidase-like activity to catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2. The catalytic mechanism was confirmed by the addition of •OH radical scavenger isopropyl alcohol (IPA), tert-butyl alcohol (TBA) and ˙OH trapping agent terephthalic acid (TA). Remarkably, the resultant blue ox-TMB system can be used to selectively and sensitively detect ascorbic acid (AA) with an LOD of 0.93 µM in the range of 4-36 µM through the colorimetric method. Moreover, the assay based on the 2-QF-CuFe-G metallohydrogel can be successfully applied to detect AA in fresh fruits.

4.
Bioorg Chem ; 143: 107103, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38211549

RESUMEN

Three undescribed (1-3) and nine known (4-12) platanosides were isolated and characterized from a bioactive extract of the May leaves of Platanus × acerifolia that initially showed inhibition against Staphylococcus aureus. Targeted compound mining was guided by an LC-MS/MS-based molecular ion networking (MoIN) strategy combined with conventional isolation procedures from a unique geographic location. The novel structures were mainly determined by 2D NMR and computational (NMR/ECD calculations) methods. Compound 1 is a rare acylated kaempferol rhamnoside possessing a truxinate unit. 6 (Z,E-platanoside) and 7 (E,E-platanoside) were confirmed to have remarkable inhibitory effects against both methicillin-resistant S. aureus (MIC: ≤ 16 µg/mL) and glycopeptide-resistant Enterococcus faecium (MIC: ≤ 1 µg/mL). These platanosides were subjected to docking analyses against FabI (enoyl-ACP reductase) and PBP1/2 (penicillin binding protein), both of which are pivotal enzymes governing bacterial growth but not found in the human host. The results showed that 6 and 7 displayed superior binding affinities towards FabI and PBP2. Moreover, surface plasmon resonance studies on the interaction of 1/7 and FabI revealed that 7 has a higher affinity (KD = 1.72 µM), which further supports the above in vitro data and is thus expected to be a novel anti-antibacterial drug lead.


Asunto(s)
Glicósidos , Staphylococcus aureus Resistente a Meticilina , Fenoles , Sepsis , Infecciones Estafilocócicas , Humanos , Antibacterianos/química , Cromatografía Liquida , Enoil-ACP Reductasa (NADH) , Pruebas de Sensibilidad Microbiana , Espectrometría de Masas en Tándem , Relación Estructura-Actividad
5.
BMC Public Health ; 24(1): 908, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38539176

RESUMEN

BACKGROUND: As the internet develops and 5G technology becomes increasingly prominent, the internet has become a major source of health-related information. Increasingly, people use the internet to find health-related information, and digital health literacy is now a set of essential capabilities to improve their health in the digital era. However, little is known about the factors that influencing digital health literacy. This study aimed to assess digital health literacy scores and identify its influencing factors among internet users in China. Additionally, this study explored the participant's actual skills using an additional set of performance-based items from the Digital Health Literacy Instrument (DHLI). METHODS: An online cross-sectional study was conducted in August 2022. Participants aged ≥18 years were recruited to complete the survey. Data were collected using the Chinese revised version of the DHLI, the self-reported internet use questionnaire, and the sociodemographic questionnaire. We conducted multivariate linear regression analyses to explore the relationships among the sociodemographic variables, behavior of internet use, and the digital health literacy scores. RESULTS: In total, 702 participants completed the survey. The mean DHLI score was 2.69 ± 0.61. Multivariate linear regression analyses showed that the age groups 35-49 (ß = - 0.08, P = 0.033), 50-64 (ß = - 0.161, P < 0.001), and ≥ 65 (ß = - 0.138, P < 0.001) were negatively associated with DHL scores. However, education level, including bachelor's or associate degree (ß = 0.255, P = 0.002) and master's degree and above (ß = 0.256, P < 0.001), frequency of health-related Internet usage (ß = 0.192, P < 0.001), the number of digital devices used (ß = 0.129, P = 0.001), and OHISB (ß = 0.103, P = 0.006) showed a positive relationship with DHL scores. CONCLUSIONS: The study findings demonstrate that age, educational levels, number of technological devices used, and greater use of the web for health information were independently associated with DHL scores. Healthcare providers should consider providing training programs tailored to specific sociodemographic factors to improve the ability that find and use accurate information online to meet digital health services, which contributes to enhance their self-management and reduce health disparities.


Asunto(s)
Alfabetización en Salud , Telemedicina , Humanos , Adolescente , Adulto , Salud Digital , Estudios Transversales , Encuestas y Cuestionarios , Internet , China
6.
Anal Chem ; 95(51): 18850-18858, 2023 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-38091507

RESUMEN

The development of chiral alignment media for measuring anisotropic NMR parameters provides an opportunity to determine the absolute configuration of chiral molecules without the need for derivatization. However, chiral alignment media with a high and robust enantiodiscriminating property for a wide range of chiral molecules are still scarce. In this study, we synthesized cholesterol-end-functionalized helical polyisocyanides from a chiral monomer using a cholesterol-based alkyne-Pd(II) initiator. These stereoregular polyisocyanides form stable and weak anisotropic lyotropic liquid crystals (LLCs) in dichloromethane systems, exhibiting highly optical activities in both single left- and right-handed helices. The preparation process of the media was straightforward, and the aligning property of the LLCs could be controlled by adjusting the concentration and temperature. Using the chiral polyisocyanides, we extracted the residual dipolar coupling for an enantiomeric pair of isopinocampheol (IPC), as well as a number of pharmaceutical molecules, demonstrating excellent enantiodiscriminating properties for a broad range of chiral compounds.

7.
J Biol Inorg Chem ; 28(2): 205-211, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36652011

RESUMEN

A facile and dual fluorescent chemosensor (named 7-IDF) based on a phenylalanine derivative with an indole group was designed and synthesized. 7-IDF can selectively and sensitively detect Zn2+ via obvious fluorescence enhancement in an aqueous solution. Remarkably, the 7-IDF-Zn complex with blue luminescence has higher selectivity toward cysteine (Cys) and histidine (His) than for other amino acids. Intriguingly, 7-IDF can also be used as an excellent probe to detect Zn2+ in real water samples. Moreover, 7-IDF and 7-IDF-Zn possess excellent biocompatibility and cell permeability, and 7-IDF can consecutively detect Zn2+ and Cys/His in Hela cells through fluorescence imaging experiments. This study suggests that the phenylalanine-based chemosensor possesses great potential applications for the sequential detection of Zn2+ and Cys/His in biosystems.


Asunto(s)
Cisteína , Colorantes Fluorescentes , Humanos , Colorantes Fluorescentes/química , Cisteína/química , Células HeLa , Histidina , Fenilalanina , Espectrometría de Fluorescencia , Zinc
8.
Inorg Chem ; 62(46): 19087-19095, 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-37934916

RESUMEN

Triplet energy transfer (TET) from semiconductor quantum dots (QDs) is an emerging strategy for sensitizing molecular triplets that have great potential in many applications. Here, CdSe QDs with varying sizes and 1-pyrenecarboxylic acid (PCA) are selected as the triplet donor and acceptor, respectively, to study the TET and charge transfer dynamics as well as enhanced singlet oxygen (1O2) generation properties. The results from static and transient spectroscopy measurements demonstrate that both the TET and hole transfer occur at the QDs-PCA interface. The observed significant drop in TET efficiency from 52 to 8% with increasing QD size results from the reduced TET driving force between the QDs and PCA, which is further confirmed by the more efficient sensitization of the anthracene derivative with a large TET driving force. In contrast, the hole transfer efficiency displays a small decrease with an increasing QD size due to a slight change in the hole driving force. The sensitized PCA triplets show a good ability of 1O2 generation, and the 1O2 formation rate increases 10-fold as the QD size decreases from 3.3 to 2.4 nm. These findings provide a profound understanding of the TET and hole transfer mechanism from QDs to molecules and are significant in designing efficient 1O2 generation systems based on semiconductor QDs and triplet molecules.

9.
Phys Chem Chem Phys ; 25(27): 18354-18363, 2023 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-37401350

RESUMEN

The construction of smart materials, especially white light emitting (WLE) hydrogels with multi-stimuli responsive properties, has received widespread attention from researchers. In this study, a WLE hydrogel was obtained by the in situ doping of Eu3+ and Tb3+ into a blue emission low molecular weight gelator (MPF). Remarkably, the prepared WLE hydrogel possessed excellent stimuli responsiveness to pH, temperature and chemicals, and could be used as a soft thermometer and a selective sensor for Cu2+. The correlated color temperature of the WLE hydrogel was calculated to be 5063 K, suggesting a potential application in cool white light. Moreover, a series of metallohydrogels with different colors were obtained by modulating the ratio of MPF, Eu3+ and Tb3+ or changing the excitation wavelength, which was an excellent candidate to construct soft materials of a full-color system. Additionally, the WLE hydrogel could be used for constructing anti-counterfeiting materials. Therefore, this study provides a new approach for preparing smart WLE hydrogels with multiple functions.

10.
Part Fibre Toxicol ; 20(1): 38, 2023 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-37807046

RESUMEN

Recently, mesoporous nanomaterials with widespread applications have attracted great interest in the field of drug delivery due to their unique structure and good physiochemical properties. As a biomimetic nanomaterial, mesoporous polydopamine (MPDA) possesses both a superior nature and good compatibility, endowing it with good clinical transformation prospects compared with other inorganic mesoporous nanocarriers. However, the subacute toxicity and underlying mechanisms of biomimetic mesoporous polydopamine nanoparticles remain uncertain. Herein, we prepared MPDAs by a soft template method and evaluated their primary physiochemical properties and metabolite toxicity, as well as potential mechanisms. The results demonstrated that MPDA injection at low (3.61 mg/kg) and medium doses (10.87 mg/kg) did not significantly change the body weight, organ index or routine blood parameters. In contrast, high-dose MPDA injection (78.57 mg/kg) is associated with disturbances in the gut microbiota, activation of inflammatory pathways through the abnormal metabolism of bile acids and unsaturated fatty acids, and potential oxidative stress injury. In sum, the MPDA dose applied should be controlled during the treatment. This study first provides a systematic evaluation of metabolite toxicity and related mechanisms for MPDA-based nanoparticles, filling the gap between their research and clinical transformation as a drug delivery nanoplatform.


Asunto(s)
Biomimética , Nanopartículas , Nanopartículas/toxicidad , Nanopartículas/química , Compuestos de Diazonio
11.
BMC Pregnancy Childbirth ; 23(1): 501, 2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37420176

RESUMEN

BACKGROUND: Threatened preterm labor (TPL) is an important obstetrical challenge. Pregnant women with TPL may develop psychological and physical problems such as mental health disorders, sleep disturbance, and hormonal circadian rhythm disruption. This study aimed to investigate the current state of mental health, sleep quality, and circadian rhythms of cortisol and melatonin secretion in pregnant women with TPL and normal pregnant women (NPW). METHODS: A prospective observational clinical study was conducted at a maternal and child health hospital in Fuzhou, China, between June and July 2022. A total of 50 women between 32 and 36 weeks of gestation (TPL group, n = 20; NPW group, n = 30) were recruited. Data on anxiety symptom (Zung's Self-rating Anxiety Scale, SAS), depression symptom (Edinburgh Postnatal Depression Scale, EPDS), subjective sleep quality (Pittsburgh Sleep Quality Index, PSQI) and objective sleep outcomes (measured by actigraphy) of the pregnant women were collected at the time of enrolment. Salivary samples were collected once every 6 h (i.e., at 06:00, 12:00, 18:00, and 00:00) during 2 consecutive days to measure the circadian rhythm of hormone (cortisol and melatonin). RESULTS: There were no differences found in the total scores of SAS, EPDS scores, subjective sleep quality between the TPL and NPW groups (P > 0.05). In contrast, significant differences were found in sleep efficiency, total sleep time, wake time after sleep onset, and average awakening time between the groups (P < 0.05). The circadian rhythm of melatonin secretion was disrupted in the TPL group (P = 0.350); however, it was maintained in the NPW group (P = 0.044). The circadian rhythm of cortisol secretion was disrupted in both groups (P > 0.05). CONCLUSIONS: In the third trimester of pregnancy, women with TPL suffer from poorer sleep quality and disruption of circadian rhythm of melatonin secretion compared with NPW. Nevertheless, there were no differences found in mental health (i.e., anxiety and depression) and circadian rhythm of cortisol secretion. Large-scale studies should be conducted to evaluate these changes in women with TPL. TRIAL REGISTRATION: The study was registered from Chinese Clinical Trial Registry (Number: ChiCTR2200060674) on 07/06/2022.


Asunto(s)
Melatonina , Trabajo de Parto Prematuro , Recién Nacido , Niño , Femenino , Humanos , Embarazo , Mujeres Embarazadas , Calidad del Sueño , Salud Mental , Hidrocortisona , Ritmo Circadiano , Sueño
12.
BMC Pregnancy Childbirth ; 23(1): 399, 2023 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-37254065

RESUMEN

BACKGROUND: Parenting sense of competence is not only indispensable to the wellbeing of the parents of premature infants, but is also pivotal to the overall development of these infants. This study examined the level of parenting sense of competence and its associated factors in Chinese parents of preterm infants. METHODS: This cross-sectional study was performed at a university teaching hospital in Fuzhou (China) from December 2021 to April 2022. Data were collected using the Parenting Sense of Competence Scale, Edinburgh Postnatal Depression Scale, Social Support Rating Scale, Parenting Care Knowledge Subscale, Parenting Care Skill Subscale, and a sociodemographic questionnaire. RESULTS: A total of 401 Chinese parents were included in the analysis. The average parenting sense of competence scale score was 70.93 ± 13.06. After controlling for demographic characteristics, parenting knowledge (ß = 0.149, P = 0.013), parenting skills (ß = 0.241, P < 0.001), social support (ß = 0.184, P < 0.001) and depression (ß = -0.272, P < 0.001), were significantly associated with the parenting sense of competence score, and explained 43.60% of the variance in this score. CONCLUSIONS: Chinese parents of preterm infants were found to have a moderate parenting sense of competence. This could be further improved through efforts aimed at reducing depressive symptoms and increasing parenting knowledge, parenting skills, and social support.


Asunto(s)
Recien Nacido Prematuro , Responsabilidad Parental , Humanos , Lactante , Recién Nacido , Estudios Transversales , Pueblos del Este de Asia , Padres
13.
Zhongguo Zhong Yao Za Zhi ; 48(19): 5315-5325, 2023 Oct.
Artículo en Zh | MEDLINE | ID: mdl-38114121

RESUMEN

This study aims to investigate the effects and the molecular mechanism of Huangdi Anxiao Capsules(HDAX)-containing serum in protecting the rat adrenal pheochromocytoma(PC12) cells from diabetes-associated cognitive dysfunction induced by high glucose and whether the mechanism is related to the regulation of NOD-like receptor thermal protein domain associated protein 3(NLRP3)-mediated pyroptosis. The PC12 cell model of diabetes-associated cognitive dysfunction induced by high glucose was established and mcc950 was used to inhibit NLRP3. PC12 cells were randomized into control, model, HDAX-containing serum, mcc950, and HDAX-containing serum+mcc950 groups. Methyl thiazolyl tetrazolium(MTT) assay was employed to determine the viability, and Hoechst 33258/PI staining to detect pyroptosis of PC12 cells. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interleukin-1 beta(IL-1ß) and IL-18. Western blot was employed to determine the protein levels of postsynaptic density protein 95(PSD-95), NLRP3, apoptosis-associated speck-like protein containing a CARD(ASC), gasdermin D(GSDMD), GSDMD-N, and cleaved cysteinyl aspartate specific proteinase-1(caspase-1), and RT-PCR to determine the mRNA levels of NLRP3, ASC, GSDMD, and caspase-1. The immunofluorescence assay was adopted to measure the levels and distribution of NLRP3 and GSDMD-N in PC12 cells. Compared with the control group, the model group showed decreased cell proliferation, increased PI positive rate, down-regulated protein level of PSD-95, up-regulated protein levels of NLRP3, ASC, GSDMD-N, GSDMD, and cleaved caspase-1, up-regulated mRNA levels of NLRP3, ASC, GSDMD, and caspase-1, and elevated levels of IL-1ß and IL-18. Compared with the model group, HDAX-containing serum, mcc950, and the combination of them improved cell survival rate and morphology, decreased the PI positive rate, down-regulated the protein levels of NLRP3, ASC, GSDMD-N, GSDMD, and cleaved caspase-1 and the mRNA levels of NLRP3, ASC, GSDMD, and caspase-1, and promoted the secretion of IL-1ß and IL-18. The findings demonstrated that HDAX-containing serum can inhibit the pyroptosis-mediated by NLRP3 and protect PC12 cells from the cognitive dysfunction induced by high glucose.


Asunto(s)
Diabetes Mellitus , Proteína con Dominio Pirina 3 de la Familia NLR , Ratas , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Interleucina-18 , Piroptosis/fisiología , Caspasas , Glucosa , ARN Mensajero
14.
Chembiochem ; 23(23): e202200531, 2022 12 05.
Artículo en Inglés | MEDLINE | ID: mdl-36217897

RESUMEN

A double mutant of human H64M/V71C neuroglobin (Ngb) was engineered, which formed a single thioether bond as that in atypical cytochrome c, whereas the heme distal Met64 was oxidized to both sulfoxide (SO-Met) and sulfone (SO2 -Met). By contrast, no Cys-heme cross-link was formed in V71C Ngb with His64/His96 coordination, as shown by the X-ray crystal structure, which indicates that an open distal site facilitates the activation of heme iron for structural modifications.


Asunto(s)
Citocromos c , Sulfuros , Humanos , Citocromos c/genética , Citocromos c/metabolismo , Hemo/química , Neuroglobina/química , Neuroglobina/metabolismo , Oxidación-Reducción , Ingeniería de Proteínas
15.
Macromol Rapid Commun ; 43(14): e2100898, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35076973

RESUMEN

The measurement of anisotropic residual dipolar couplings (RDCs) parameters for the structure elucidation of organic molecules relies on suitable alignment media. Employment of self-assembled liquid crystalline systems to create anisotropic alignment can be an effective way to realize aligned samples and acquire RDCs. This Mini-review highlights the recent advances on amino acid-based helical polymers and supramolecular oligomers forming rigid, rod-like structures that aggregate into ordered liquid crystalline phases, including amino acid-based helical polyisocyanides, polyacetylenes, polypeptides, and oligopeptides assembled alignment media. The methodology for the determination of anisotropic liquid crystals is briefly discussed, and a summary of recent research progress in the enantiodifferentiation of helical polymers aligned media is followed. In addition, the self-assembled mechanism of oligopeptides and their RDCs structural analysis are also described.


Asunto(s)
Cristales Líquidos , Aminoácidos , Cristales Líquidos/química , Espectroscopía de Resonancia Magnética/métodos , Oligopéptidos , Polímeros
16.
Acta Pharmacol Sin ; 43(8): 1916-1927, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34893682

RESUMEN

PTEN-induced putative kinase 1 (PINK1)/parkin pathway mediates mitophagy, which is a specialized form of autophagy. Evidence shows that PINK1 can exert protective effects against stress-induced neuronal cell death. In the present study we investigated the effects of PINK1 overexpression on tau hyperphosphorylation, mitochondrial dysfunction and oxidative stress in a specific rat model of tau hyperphosphorylation. We showed that intracerebroventricular (ICV) microinjection of forskolin (FSK, 80 µmol) induced tau hyperphosphorylation in the rat brain and resulted in significant spatial working memory impairments in Y-maze test, accompanied by synaptic dysfunction (reduced expression of synaptic proteins synaptophysin and postsynaptic density protein 95), and neuronal loss in the hippocampus. Adeno-associated virus (AAV)-mediated overexpression of PINK1 prevented ICV-FSK-induced cognition defect and pathological alterations in the hippocampus, whereas PINK1-knockout significantly exacerbated ICV-FSK-induced deteriorated effects. Furthermore, we revealed that AAV-PINK1-mediated overexpression of PINK1 alleviated ICV-FSK-induced tau hyperphosphorylation by restoring the activity of PI3K/Akt/GSK3ß signaling. PINK1 overexpression reversed the abnormal changes in mitochondrial dynamics, defective mitophagy, and decreased ATP levels in the hippocampus. Moreover, PINK1 overexpression activated Nrf2 signaling, thereby increasing the expression of antioxidant proteins and reducing oxidative damage. These results suggest that PINK1 deficiency exacerbates FSK-induced tau pathology, synaptic damage, mitochondrial dysfunction, and antioxidant system defects, which were reversed by PINK1 overexpression. Our data support a critical role of PINK1-mediated mitophagy in controlling mitochondrial quality, tau hyperphosphorylation, and oxidative stress in a rat model of Alzheimer's disease.


Asunto(s)
Enfermedad de Alzheimer , Estrés Oxidativo , Proteínas Quinasas , Proteínas tau , Enfermedad de Alzheimer/metabolismo , Animales , Antioxidantes/metabolismo , Colforsina , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Quinasas/metabolismo , Ratas , Ubiquitina-Proteína Ligasas/metabolismo , Proteínas tau/metabolismo
17.
Nucleic Acids Res ; 48(D1): D307-D313, 2020 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-31598693

RESUMEN

RNA binding proteins (RBPs) are a large protein family that plays important roles at almost all levels of gene regulation through interacting with RNAs, and contributes to numerous biological processes. However, the complete list of eukaryotic RBPs including human is still unavailable. Here, we systematically identified RBPs in 162 eukaryotic species based on both computational analysis of RNA binding domains (RBDs) and large-scale RNA binding proteomic data, and established a comprehensive eukaryotic RBP database, EuRBPDB (http://EuRBPDB.syshospital.org). We identified a total of 311 571 RBPs with RBDs (corresponding to 6368 ortholog groups) and 3,651 non-canonical RBPs without known RBDs. EuRBPDB provides detailed annotations for each RBP, including basic information and functional annotation. Moreover, we systematically investigated RBPs in the context of cancer biology based on published literatures, PPI-network and large-scale omics data. To facilitate the exploration of the clinical relevance of RBPs, we additionally designed a cancer web interface to systematically and interactively display the biological features of RBPs in various types of cancers. EuRBPDB has a user-friendly web interface with browse and search functions, as well as data downloading function. We expect that EuRBPDB will be a widely-used resource and platform for both the communities of RNA biology and cancer biology.


Asunto(s)
Neoplasias , Proteínas de Unión al ARN/química , Proteínas de Unión al ARN/metabolismo , Bases de Datos de Proteínas , Eucariontes , Humanos , Internet , Mutación , Neoplasias/química , Motivos de Unión al ARN , Proteínas de Unión al ARN/genética
18.
Molecules ; 27(23)2022 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-36500571

RESUMEN

Heme proteins perform a variety of biological functions and also play significant roles in the field of bio-catalysis. The ß-lactamase activity of heme proteins has rarely been reported. Herein, we found, for the first time, that myoglobin (Mb), an O2 carrier, also exhibits novel ß-lactamase activity by catalyzing the hydrolysis of ampicillin. The catalytic proficiency ((kcat/KM)/kuncat) was determined to be 6.25 × 1010, which is much higher than the proficiency reported for designed metalloenzymes, although it is lower than that of natural ß-lactamases. Moreover, we found that this activity could be regulated by an engineered disulfide bond, such as Cys46-Cys61 in F46C/L61C Mb or by the addition of imidazole to directly coordinate to the heme center. These results indicate that the heme active site is responsible for the ß-lactamase activity of Mb. Therefore, the study suggests the potential of heme proteins acting as ß-lactamases, which broadens the diversity of their catalytic functions.


Asunto(s)
Hemo , Mioglobina , Mioglobina/química , Hemo/química , Conformación Proteica , Modelos Moleculares , beta-Lactamasas/genética , beta-Lactamasas/metabolismo
19.
Molecules ; 27(14)2022 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-35889429

RESUMEN

Imbalance in the cellular redox system is thought to be associated with the induction and progression of breast cancers, and heme proteins may regulate the redox balance. Cytochrome b5 (Cyt b5) is a small mitochondrial heme protein. Its function and regulating mechanism in breast cancer remain unknown. In this study, we elucidated the level of endogenous oxidative stress in breast cancer cells, MCF-7 cells (hormone receptor-positive cells) and MDA-MB-231 cells (triple-negative cells), and investigated the difference in Cyt b5 content. Based on the low content of Cyt b5 in MDA-MB-231 cells, the overexpression of Cyt b5 was found to regulate the oxidative stress and apoptosis cascades, including ERK1/2 and Akt signaling pathways. The overexpressed Cyt b5 MDA-MB-231 cells were shown to exhibit decreased oxidative stress, less phosphorylation of ERK1/2 and Akt, and less cleavage of caspases 3 and 9 upon treatment with H2O2, as compared to those of normal MDA-MB-231 cells. Moreover, the overexpressed Cyt b5 most likely functioned by interacting with its protein partner, Cyt c, as suggested by co-immunoprecipitation studies. These results indicated that Cyt b5 has different effects on breast cancer cells of different phenotypes, which provides useful information for understanding the multiple roles of Cyt b5 and provides clues for clinical treatment.


Asunto(s)
Neoplasias de la Mama , Citocromos b5 , Neoplasias de la Mama/genética , Citocromos b5/genética , Citocromos b5/metabolismo , Femenino , Humanos , Peróxido de Hidrógeno/farmacología , Proteínas Proto-Oncogénicas c-akt/genética
20.
BMC Infect Dis ; 21(1): 314, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33794779

RESUMEN

BACKGROUND: Older patients hospitalized with community-acquired pneumonia (CAP) are at high risk for short-term mortality. Activity of daily living (ADL) is associated with clinical outcomes in older patients. We aimed to investigate the prognostic value of ADL upon admission on the in-hospital mortality in older patients with CAP. METHODS: We conducted a retrospective cohort study involving patients aged ≥65 years admitted to Beijing Chao-Yang hospital due to CAP between June 2012 and June 2020. ADL evaluation upon admission was performed by Barthel Index (BI). Data from all patients were extracted from the electronic medical records. RESULTS: Four thousand eight hundred eighty patients were included, 131 patients (2.7%) died during their hospitalization. Median BI in the Deceased group was 45 (20-65), Deceased group had lower BI scores than Survivors group (p < 0.001). Low BI (< 60) was more frequent in patients who died in the hospital than in patients discharged alive (69.5% vs. 13%, p < 0.001). In-hospital mortality was higher among patients with worse ADL upon admission (BI< 60) compared to those BI≥60 (12.6% vs. 0.9%). The worse ADL upon admission (BI< 60) was associated with an increase in the risk of death during CAP hospitalization, worse ADL upon admission (BI< 60) showed an odds ratio (OR) for in-hospital mortality of 7.53 (95%CI: 2.77-20.48; P < 0.01). This association remained significant after adjustment for age, comorbid conditions, respiratory failure, pathogens and laboratory findings (OR, 3.74; 95%CI, 2.37-5.91; P < 0.01). Receiver operating characteristic (ROC) curve revealed that BI upon admission is a predictor related to in-hospital mortality in elderly patients, the area under the ROC curve of BI in predicting in-hospital mortality was 0.81 (with 95% confidence interval: 0.78-0.85). The predictive value of ADL upon admission was better than age in our study population. CONCLUSION: Activity of daily living upon admission is an independent predictor of in-hospital mortality in older patients with community-acquired pneumonia.


Asunto(s)
Actividades Cotidianas , Infecciones Comunitarias Adquiridas/mortalidad , Neumonía/mortalidad , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Infecciones Comunitarias Adquiridas/diagnóstico , Comorbilidad , Femenino , Mortalidad Hospitalaria , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Oportunidad Relativa , Neumonía/diagnóstico , Pronóstico , Curva ROC , Estudios Retrospectivos
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