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Over 150 types of chemical modifications have been identified in RNA to date, with pseudouridine (Ψ) being one of the most prevalent modifications in RNA. Ψ plays vital roles in various biological processes, and precise, base-resolution detection methods are fundamental for deep analysis of its distribution and function. In this study, we introduced a novel base-resolution Ψ detection method named pseU-TRACE. pseU-TRACE relied on the fact that RNA containing Ψ underwent a base deletion after treatment of bisulfite (BS) during reverse transcription, which enabled efficient ligation of two probes complementary to the cDNA sequence on either side of the Ψ site and successful amplification in subsequent real-time quantitative PCR (qPCR), thereby achieving selective and accurate Ψ detection. Our method accurately and sensitively detected several known Ψ sites in 28S, 18S, 5.8S, and even mRNA. Moreover, pseU-TRACE could be employed to measure the Ψ fraction in RNA and explore the Ψ metabolism of different pseudouridine synthases (PUSs), providing valuable insights into the function of Ψ. Overall, pseU-TRACE represents a reliable, time-efficient and sensitive Ψ detection method.
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Seudouridina , Reacción en Cadena en Tiempo Real de la Polimerasa , Sulfitos , Humanos , Seudouridina/química , Seudouridina/genética , Seudouridina/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , ARN/química , ARN/genética , ARN Mensajero/genética , ARN Mensajero/química , ARN Mensajero/metabolismo , Sulfitos/químicaRESUMEN
INTRODUCTION: Circular RNAs (CircRNA) have emerged as an interest of research in recent years due to its regulatory role in various kinds of cancers of human body. Esophageal squamous cell carcinoma (ESCC) is one of the major disease subtype in Asian countries, including China. CircRNAs are formed by back-splicing covalently joined 3'- and 5'- ends rather than canonical splicing and are found to have binding affinity with miRNAs that conjointly contribute to oncogenesis. MATERIALS AND METHODS: 4 pairs of normal, cancer adjacent tissues and cancer tissues were analyzed by high-throughput RNA sequencing and 84 differentially upregulated circRNAs were detected in cancer tissues. hsa_circ_0032746 was silenced by siRNA and lentivirus and then further proliferation, migration and invasion were performed by CCK-8 and transwell assays. Bioinformatic analysis predicted binding affinity of circRNA/miRNA/mRNA axis. RESULTS: After qPCR validation, we selected a novel upregulated hsa_circ_0032746 to explore its biogenetic functions which showed high expression in cancer tissues but not in cancer adjacent tissues. The clinicopathological relation of hsa_circ_0032746 showed positive correlation with the tumor location (P = 0.026) and gender (P = 0.05). We also predicted that hsa_circ_0032746 could sponge with microRNA. Bioinformatic analysis predicted 11 microRNA response element (MRE) sequences of hsa_circ_0032746 and dual luciferase reporter assay confirmed binding affinity with miR4270 evidencing further study of circRNA/miRNA role. The knockdown of hsa_circ_0032746 by siRNA and lentivirus demonstrated that proliferation, invasion and migration of ESCC were inhibited in vitro and vivo experiments. Bioinformatic analysis further predicted MCM3 as a target of miR-4270 and was found upregulated in ESCC upon validation. miR4270 mimic decreased the level of hsa_circ_0032746 and MCM3 while further rescue experiments demonstrated that hsa_circ_0032746 was dependent on miR4270/MCM3 axis on the development process of ESCC. CONCLUSION: We revealed for the first time that circ_0032746/mir4270/MCM3 contributes in proliferation, migration and invasion of ESCC and could have potential prognostic and therapeutic significance.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , MicroARNs , Humanos , ARN Circular/genética , Carcinoma de Células Escamosas de Esófago/genética , Neoplasias Esofágicas/genética , Carcinogénesis/genética , MicroARNs/genética , ARN Interferente Pequeño , Componente 3 del Complejo de Mantenimiento de MinicromosomaRESUMEN
As an integral lysosomal transmembrane protein, transmembrane protein 106B (TMEM106B) regulates several aspects of lysosomal function and is associated with neurodegenerative diseases. The TMEM106B gene mutations lead to lysosomal dysfunction and accelerate the pathological progression of Neurodegenerative diseases. Yet, the precise mechanism of TMEM106B in Neurodegenerative diseases remains unclear. Recently, different research teams discovered that TMEM106B is an amyloid protein and the C-terminal domain of TMEM106B forms amyloid fibrils in various Neurodegenerative diseases and normally elderly individuals. In this review, we discussed the physiological functions of TMEM106B. We also included TMEM106B gene mutations that cause neurodegenerative diseases. Finally, we summarized the identification and cryo-electronic microscopic structure of TMEM106B fibrils, and discussed the promising therapeutic strategies aimed at TMEM106B fibrils and the future directions for TMEM106B research in neurodegenerative diseases.
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Proteínas de la Membrana , Proteínas del Tejido Nervioso , Enfermedades Neurodegenerativas , Animales , Humanos , Amiloide/metabolismo , Amiloide/genética , Amiloide/química , Lisosomas/metabolismo , Lisosomas/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/química , Mutación , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/química , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/patologíaRESUMEN
A multiple sub-pupil ultra-spectral imaging system designed with a single spectrometer and detector can simultaneously detect multiple-channel spectra with ultra-high spectral resolution. However, due to using a prism in the system's front end, the nonlinear dispersion introduces spectral line tilt in the imaging spectra. This phenomenon can lead to bias in the final spectral data. To eliminate this issue, we propose a new design by introducing a second prism to correct this spectral tilt in the system. The angle of spectral line tilt generated by the nonlinear dispersion of the first prism is derived. It provides the theoretical basis for characterizing the second complementary prism. Finally, a UV multiple sub-pupil ultra-spectral imaging system is designed. The system employs two pupil separation prisms and one flat panel array to segment the pupil in three channels, each operating within spectral ranges of 180â¼210â nm, 275â¼305â nm, and 370â¼400â nm, respectively. The spectral resolutions in all three channels are better than 0.1â nm. The corrected spectral line tilt is less than 1/3 of a pixel in the two channels with pupil separation prisms. At a Nyquist frequency of 30 lp/mm, the modulation transfer functions of all three channels are greater than 0.7, ensuring imaging quality. The design results indicate that the method proposed in this paper, utilizing complementary prisms, can effectively correct the spectral line tilt caused by the nonlinear dispersion of the pupil separation prisms. This design approach can be a reference for developing multiple sub-pupil ultra-spectral imaging systems.
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PURPOSE/AIM OF THE STUDY: To summarize and discuss macrophage properties and their roles and mechanisms in the process of osseointegration in a comprehensive manner, and to provide theoretical support and research direction for future implant surface modification efforts. MATERIALS AND METHODS: Based on relevant high-quality articles, this article reviews the role of macrophages in various stages of osseointegration and methods of implant modification. RESULTS AND CONCLUSIONS: Macrophages not only promote osseointegration through immunomodulation, but also secrete a variety of cytokines, which play a key role in the angiogenic and osteogenic phases of osseointegration. There is no "good" or "bad" difference between the M1 and M2 phenotypes of macrophages, but their timely presence and sequential switching play a crucial role in implant osseointegration. In the implant surface modification strategy, the induction of sequential activation of the M1 and M2 phenotypes of macrophages is a brighter prospect for implant surface modification than inducing the polarization of macrophages to the M1 or M2 phenotypes individually, which is a promising pathway to enhance the effect of osseointegration and increase the success rate of implant surgery.
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Macrófagos , Oseointegración , Macrófagos/metabolismo , Citocinas/metabolismo , Prótesis e Implantes , Osteogénesis , Titanio/metabolismo , Propiedades de SuperficieRESUMEN
The total syntheses of (±)-quebrachamine and (±)-kopsiyunnanine D are reported. Key transformations include an intermolecular Horner-Wadsworth-Emmons olefination to merge the two fragments convergently and an intramolecular Mitsunobu reaction to introduce the synthetically challenging nine-membered azonane ring efficiently.
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INTRODUCTION: The effect of nutritional status on osteosarcopenia (OS) and major osteoporotic fracture (MOF) among the elderly is still unclear. So we aimed to compare the efficacy of the Mini-Nutrition Assessment-Short Form (MNA-sf), the Geriatric Nutritional Risk Index (GNRI) and Controlling Nutritional Status (CONUT) for predicting OS and MOF among the elderly. MATERIALS AND METHODS: A total of 409 participants were enrolled in this prospective study. Blood biochemical indexes, nutritional status, and bone- and muscle-related examinations were assessed at initial visit to the outpatient. Participants were divided into 4 groups: (1) control; (2) osteopenia/osteoporosis; (3) sarcopenia; (4) osteosarcopenia, and then followed for 5 years, recording the occurrence time of MOF. RESULTS: The frequency values of osteopenia/osteoporosis, sarcopenia, and OS, at baseline, were respectively 13.4, 16.1, and 12% among the study samples. Correlation analysis showed that nutritional status scores were associated with body mass index, handgrip strength, albumin, bone mineral density, and physical functions. According to multivariate models, poor nutritional status was significantly associated with a higher risk of OS and MOF (P < 0.05). Survival analysis showed that the MOF rate in malnutrition group was significantly higher than normal nutrition group (P < 0.05). The receiver operator characteristic curve shows that the value of MNA-sf to diagnose OS and MOF is greater (P < 0.05). CONCLUSION: The poor nutritional status was associated with a higher risk of both OS and MOF. MNA-sf showed a superior diagnostic power for OS and MOF among the elderly. Early nutrition assessments and interventions may be key strategies to prevent OS and fractures.
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Estado Nutricional , Fracturas Osteoporóticas , Sarcopenia , Humanos , Sarcopenia/sangre , Sarcopenia/diagnóstico , Sarcopenia/epidemiología , Anciano , Femenino , Masculino , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/sangre , Incidencia , Estudios Prospectivos , Evaluación Nutricional , Anciano de 80 o más Años , Enfermedades Óseas Metabólicas/epidemiología , Enfermedades Óseas Metabólicas/sangre , Densidad Ósea , Osteoporosis/epidemiología , Osteoporosis/sangre , Osteoporosis/diagnóstico , Persona de Mediana EdadRESUMEN
INTRODUCTION: To investigate the clinical value of serum albumin to alkaline phosphatase ratio (AAPR) in predicting the risk of osteoporotic vertebral refractures group (OVRFs) after percutaneous vertebral augmentation (PVA) in postmenopausal women. MATERIALS AND METHODS: This is a retrospective case-control study including a series of postmenopausal women patients with osteoporotic vertebral fracture (OVF) and underwent PVA. Patients were divided into OVRFs and non-OVRFs. COX model was used to evaluate the correlation between preoperative AAPR and OVRFs after PVA. The receiver operating characteristic (ROC) curve and Kaplan-Meier method were used to analyze the predictive value of AAPR for the incidence of OVRFs. RESULTS: A total of 305 patients were included in the final study, and the incidence of postoperative OVRFs was 28.9%. Multivariate COX analysis showed that advanced age (HRs = 1.062, p = 0.002), low BMI (HRs = 0.923, p = 0.036), low AAPR (HRs = 0.019, p = 0.001), previous fall history (HRs = 3.503, p = 0.001), denosumab treatment (HRs = 0.409, p = 0.007), low L3 BMD (HRs = 0.977, p = 0.001) and low L3 paravertebral muscle density (PMD)value (HRs = 0.929, p = 0.001)) were closely related to the incidence of OVRFs. The area under the curve (AUC) of AAPR for predicting OVRFs was 0.740 (p < 0.001), and the optimal diagnostic cut-off value was 0.49. Kaplan-Meier curve analysis showed that low AAPR group (< 0.49) was significantly associated with lower OVRFs-free survival (p = 0.001; log-rank test). CONCLUSION: AAPR is an independent risk factor for OVRFs after PVA in postmenopausal women, and it can be used as an effective index to predict OVRFs.
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Two-dimensional double perovskites have experienced rapid development due to their outstanding optoelectronic properties and diverse structural characteristics. However, the synthesis of high-performance multifunctional compounds and the regulation of their properties still lack relevant examples. Herein, we synthesized two multifunctional compounds, (C6H14N)4AgSbBr8 (1) and (F2-C6H12N)4AgSbBr8 (2), which exhibit high solid-state phase transition temperature, bistable dielectric constant switching, second harmonic generation (SHG), and bright emission. Through H/F substitution, the transition temperature increases and achieves a smaller band gap attributed to reduced interlayer spacing. Furthermore, we investigated the broad emission mechanism of the compounds through first-principles calculation and variable-temperature fluorescence, confirming the presence of the STE1 emission. Our work provides insight into the further development of multifunctional compounds and chemical modification that enhances compound properties.
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Prenatal per and polyfluoroalkyl substances (PFAS) exposure is associated with adverse birth outcomes. There is an absence of evidence on the relationship between maternal and paternal preconception PFAS exposure and birth outcomes. This study included 312 mothers and 145 fathers with a singleton live birth from a preconception cohort of subfertile couples seeking fertility treatment at a U.S. clinic. PFAS were quantified in serum samples collected before conception. Gestational age (GA) and birthweight (BW) were abstracted from delivery records. We also assessed low birthweight (BW < 2500 g) and preterm birth (GA < 37 completed weeks). We utilized multivariable linear regression, logistic regression, and quantile-based g computation to examine maternal or paternal serum concentrations of individual PFAS and mixture with birth outcomes. Maternal serum concentrations of perfluorooctanesulfonate (PFOS), perfluorohexanesulfonate (PFHxS), and the total PFAS mixture were inversely associated with birthweight. Maternal PFOS concentration was associated with a higher risk of low birthweight. Conversely, paternal PFOS and PFHxS concentrations were imprecisely associated with higher birthweight. No associations were found for gestational age or preterm birth. The findings have important implications for preconception care. Future research with larger sample sizes would assist in validating these findings.
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Ácidos Alcanesulfónicos , Contaminantes Ambientales , Fluorocarburos , Nacimiento Prematuro , Masculino , Embarazo , Femenino , Humanos , Recién Nacido , Peso al Nacer , Nacimiento Prematuro/epidemiología , PadreRESUMEN
Eleven undescribed monoterpenoid bisindole alkaloids, alstomaphyines A-K (1-11), along with three known analogues were isolated from the leaves and stem bark of the Alstonia macrophylla. Compounds 1-3 were unprecedented dimerization alkaloids incorporating a macroline-type motif with an ajmaline-type motif via a C-C linkage. Their structures and absolute configurations were elucidated by extensive spectroscopic analysis, electronic circular dichroism (ECD) calculation, and CD exciton chirality method. Compounds 1-3 displayed potential inhibitory bioactivity against AChE with IC50 values of 4.44 ± 0.35, 3.59 ± 0.18, and 3.71 ± 0.23 µM, respectively. Enzyme kinetic study revealed compounds 1-3 as mixed competitive AChE inhibitors. Besides, compounds 8 and 12-14 exhibited better cytotoxicity against human cancer cell line HT-29 than cisplatin. Flow cytometry data revealed that compounds 8, 13, and 14 significantly induced the HT-29 cells arrest in G0/G1 phase in a concentration-dependent manner.
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Endometrial carcinoma is one of most common malignant tumors in women, and ferroptosis is closely related to the development and treatment of endometrial carcinoma. The aim of this study was to screen ferroptosis-related genes associated with endometrial carcinoma and predict targeted drugs through bioinformatics. 761 differentially expressed genes were obtained by the dataset GSE63678 from the GEO database, and most of the genes were enriched in the KEGG_CELL_CYCLE and KEGG_OOCYTE_MEIOSIS signaling pathways. 22 ferroptosis-differentially expressed genes were obtained by intersection with the FerrDb database. These genes were involved in biological processes including macromolecular complex assembly and others, and involved in signal pathways including glutathione metabolism, p53 signaling pathway and others. CDKN2A, IDH1, NRAS, TFRC and GOT1 were obtained as hub genes by PPI network analysis. GEPIA showed that CDKN2A, IDH1, NRAS and TFRC were significantly expressed in endometrial carcinoma. Immunohistochemical results showed that CDKN2A, NRAS and TFRC were significantly expressed in endometrial carcinoma clinical tissue samples. The ROC constructed by TCGA database showed that CDKN2A, NRAS and TFRC had significant value in the diagnosis of endometrial carcinoma, and all had prognostic efficacy. 136,572-09-3 BOSS and others were identified as potential targeted drugs for endometrial carcinoma targeting ferroptosis. Our study has shown that ferroptosis-related genes CDKN2A, NRAS and TFRC are diagnostic markers of endometrial carcinoma, and 136,572-09-3 BOSS, methyprylon BOSS, daunorubicin CTD 00005752, nitroglycerin BOSS and dUTP BOSS, IRON BOSS, Imatinib mesylate BOSS, 2-Butanone BOSS, water BOSS, and L-thyroxine BOSS may be potential therapeutic drugs.
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Biología Computacional , Neoplasias Endometriales , Ferroptosis , Femenino , Ferroptosis/efectos de los fármacos , Ferroptosis/genética , Humanos , Neoplasias Endometriales/genética , Neoplasias Endometriales/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , GTP Fosfohidrolasas/genética , Biomarcadores de Tumor/genética , Proteínas de la Membrana/genética , Receptores de Transferrina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Mapas de Interacción de Proteínas , Bases de Datos Genéticas , Antígenos CDRESUMEN
BACKGROUND: Sitosterolemia, an autosomal recessive condition, is characterized by impaired metabolism of plant sterols. Clinical symptoms include skin xanthoma, premature atherosclerotic disease, arthritis, and unexplained hematological abnormalities. However, there is a dearth of studies on sitosterolemia-related brain damage. METHODS: This study focused on the family of two sitosterolemia patients who presented with severe hypercholesterolemia and xanthoma. Radiological examinations, biopsies, whole-exome sequencing (WES), and plant sterol tests were conducted. RESULTS: The index patient, a 66-year-old female, initially exhibited weakness in both lower limbs and later developed urinary and fecal incontinence. Neuroimaging showed that the falx of the brain had irregular fusiform thickening. Significant tissue edema was observed around the lesions in the bilateral frontal-parietal lobes. Pathological analysis of the biopsied brain lesion revealed extensive cholesterol crystal deposition and lymphocyte infiltration in the matrix. The index patient who experienced cerebral impairment and her sister both carried two compound heterozygous variants in ATP binding cassette transporter G5 (ABCG5). These included the nonsense variants NM_022436: c.751 C > T (p.Q251X) in exon 6 and NM_022436: c.1336 C > T (p.R446X) in exon 10. A notable increase in plant sterol levels was observed in the younger sister of the index patient. CONCLUSION: This study highlights a previously unreported neurological aspect of sitosterolemia. Imaging and pathology findings suggest that cholesterol crystals may be deposited in connective tissues such as the cerebral falx and pia mater through blood circulation.
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Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 5 , Hipercolesterolemia , Enfermedades Intestinales , Errores Innatos del Metabolismo Lipídico , Fitosteroles , Humanos , Femenino , Fitosteroles/efectos adversos , Anciano , Hipercolesterolemia/genética , Hipercolesterolemia/patología , Hipercolesterolemia/complicaciones , Errores Innatos del Metabolismo Lipídico/genética , Errores Innatos del Metabolismo Lipídico/patología , Errores Innatos del Metabolismo Lipídico/diagnóstico por imagen , Enfermedades Intestinales/genética , Enfermedades Intestinales/patología , Enfermedades Intestinales/diagnóstico por imagen , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 5/genética , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Secuenciación del Exoma , Xantomatosis/patología , Xantomatosis/genética , Xantomatosis/diagnóstico por imagen , Linaje , Colesterol/sangre , Masculino , Sitoesteroles , LipoproteínasRESUMEN
OBJECTIVE: This study aimed to investigate the expression of tight junction, its distribution pattern in oral lichen planus samples and its potential association with the severity of oral lichen planus. MATERIALS AND METHODS: Cross-sectional study designs were conducted. Transcriptome sequencing was conducted using oral mucosal tissues from 22 patients with oral lichen planus and 11 healthy controls. Immunohistochemistry and quantitative reverse transcription PCR were performed to verify the expression of claudin-1, claudin-4, occludin and zonula occludens-1 in oral mucosal tissues from another 30 patients with oral lichen planus and 26 healthy controls. The relationship between tight junction protein expression and oral lichen planus severity was explored using correlation analysis. RESULTS: 5603 and 2475 differentially expressed genes were upregulated and downregulated respectively, in oral lichen planus tissues. KEGG analysis showed that tight junctions including CLDN1, CLDN4, OCLN and TJP1 were downregulated in oral lichen planus. Claudin-1, claudin-4, occludin and zonula occludens-1 expression was verified to be significantly lower in oral lichen planus. Furthermore, correlation analyses showed that decreased occludin expression was positively related to oral lichen planus severity. CONCLUSION: Decreased expression of TJ barrier proteins may be associated with the development of oral lichen planus.
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Endothelial hyperpermeability is pivotal in sepsis-associated multi-organ dysfunction. Increased von Willebrand factor (vWF) plasma levels, stemming from activated platelets and endothelium injury during sepsis, can bind to integrin αvß3, exacerbating endothelial permeability. Hence, targeting this pathway presents a potential therapeutic avenue for sepsis. Recently, we identified isaridin E (ISE), a marine-derived fungal cyclohexadepsipeptide, as a promising antiplatelet and antithrombotic agent with a low bleeding risk. ISE's influence on septic mortality and sepsis-induced lung injury in a mouse model of sepsis, induced by caecal ligation and puncture, is investigated in this study. ISE dose-dependently improved survival rates, mitigating lung injury, thrombocytopenia, pulmonary endothelial permeability, and vascular inflammation in the mouse model. ISE markedly curtailed vWF release from activated platelets in septic mice by suppressing vesicle-associated membrane protein 8 and soluble N-ethylmaleide-sensitive factor attachment protein 23 overexpression. Moreover, ISE inhibited healthy human platelet adhesion to cultured lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), thereby significantly decreasing vWF secretion and endothelial hyperpermeability. Using cilengitide, a selective integrin αvß3 inhibitor, it was found that ISE can improve endothelial hyperpermeability by inhibiting vWF binding to αvß3. Activation of the integrin αvß3-FAK/Src pathway likely underlies vWF-induced endothelial dysfunction in sepsis. In conclusion, ISE protects against sepsis by inhibiting endothelial hyperpermeability and platelet-endothelium interactions.
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Plaquetas , Células Endoteliales de la Vena Umbilical Humana , Sepsis , Factor de von Willebrand , Animales , Sepsis/tratamiento farmacológico , Factor de von Willebrand/metabolismo , Humanos , Ratones , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Masculino , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Integrina alfaVbeta3/metabolismo , Integrina alfaVbeta3/antagonistas & inhibidores , Permeabilidad Capilar/efectos de los fármacosRESUMEN
To clarify the chemical basis of the total alkaloids of Uncaria rhynchophylla, HPLC-VWD chromatogram of total alkaloids was established. Under its guidance, modern chromatographic and spectroscopic techniques were used to track, isolate and identify the representative principal components. As a result, one new monoterpenoid indole alkaloid, 3S,15S-N4-methoxymethyl-geissoschizine methyl ether (1), together with 20 known alkaloids (2-21), and 5 other known compounds (22-26) were obtained. Meanwhile, sixteen characteristic peaks were identified from the total alkaloids using HPLC analysis. Then, the anti-neuroinflammatory effect of compounds 1-21 was assessed through inhibiting nitric ---oxide (NO) production in lipopolysaccharide (LPS)-induced BV-2 microglial cells. Among them, compounds 1, 3, 7, 8, 11, 12, 19 and 21 showed potent inhibitory activities with IC50 values of 5.87-76.78 µM.
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Alcaloides , Antiinflamatorios , Alcaloides Indólicos , Lipopolisacáridos , Microglía , Óxido Nítrico , Uncaria , Uncaria/química , Estructura Molecular , Alcaloides/farmacología , Alcaloides/química , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Antiinflamatorios/farmacología , Antiinflamatorios/química , Lipopolisacáridos/farmacología , Microglía/efectos de los fármacos , Animales , Ratones , Cromatografía Líquida de Alta Presión , Alcaloides de Triptamina Secologanina/farmacología , Alcaloides de Triptamina Secologanina/químicaRESUMEN
Four new alkaloids, arecatines A-D (1-4), were isolated from the peels of Areca catechu. Compound 1 is an unusual piperidine-pyridine hybrid alkaloid, whereas compounds 2-4 feature bis-piperidine alkaloids. Their structures were elucidated by UV, IR, HRESIMS, and NMR spectra analysis. The molecular docking analysis indicated that compound 3 exhibited the best binding affinity with the GABAA receptor, indicating its potential anti-epilepsy activity.
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Phytophthora root rot is a devastating disease of soybean caused by Phytophthora sojae. However, the resistance mechanism is not yet clear. Our previous studies have shown that GmAP2 enhances sensitivity to P. sojae in soybean, and GmMYB78 is downregulated in the transcriptome analysis of GmAP2-overexpressing transgenic hairy roots. Here, GmMYB78 was significantly induced by P. sojae in susceptible soybean, and the overexpressing of GmMYB78 enhanced sensitivity to the pathogen, while silencing GmMYB78 enhances resistance to P. sojae, indicating that GmMYB78 is a negative regulator of P. sojae. Moreover, the jasmonic acid (JA) content and JA synthesis gene GmAOS1 was highly upregulated in GmMYB78-silencing roots and highly downregulated in overexpressing ones, suggesting that GmMYB78 could respond to P. sojae through the JA signaling pathway. Furthermore, the expression of several pathogenesis-related genes was significantly lower in GmMYB78-overexpressing roots and higher in GmMYB78-silencing ones. Additionally, we screened and identified the upstream regulator GmbHLH122 and downstream target gene GmbZIP25 of GmMYB78. GmbHLH122 was highly induced by P. sojae and could inhibit GmMYB78 expression in resistant soybean, and GmMYB78 was highly expressed to activate downstream target gene GmbZIP25 transcription in susceptible soybean. In conclusion, our data reveal that GmMYB78 triggers soybean sensitivity to P. sojae by inhibiting the JA signaling pathway and the expression of pathogenesis-related genes or through the effects of the GmbHLH122-GmMYB78-GmbZIP25 cascade pathway.
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Ciclopentanos , Resistencia a la Enfermedad , Regulación de la Expresión Génica de las Plantas , Glycine max , Oxilipinas , Phytophthora , Enfermedades de las Plantas , Proteínas de Plantas , Factores de Transcripción , Glycine max/genética , Glycine max/microbiología , Glycine max/parasitología , Glycine max/metabolismo , Phytophthora/patogenicidad , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/parasitología , Enfermedades de las Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Plantas Modificadas Genéticamente , Raíces de Plantas/microbiología , Raíces de Plantas/genética , Raíces de Plantas/parasitología , Raíces de Plantas/metabolismoRESUMEN
BACKGROUND: Enshi Yulu tea (ESYL) is the most representative of steamed green tea in China, but its aroma formation in processing is unclear. Thus, the ESYL volatiles during the whole industrial processing were investigated using headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry. RESULTS: A total of 134 volatiles were identified. Among these, 31 differential volatiles [P < 0.05 and variable importance in projection (VIP) > 1] and 25 key volatiles [relative odor activity value (rOAV) and/or the ratio of each rOAV to the maximum rOAV (ROAV) > 1.0] were screened out, wherein ß-ionone and nonanal were the most key odorants. Besides, the sensory evaluation combined with multivariate statistical analysis of volatiles pinpointed spreading, fixation, first drying, and second drying as the key processing steps that have a pronounced influence on the aroma quality of ESYL. Furthermore, the oxidative degradation of unsaturated fatty acids, synthesis of monoterpenes, and degradation of carotenoids were the main metabolic pathway for the formation of key odorants. CONCLUSION: The study provides comprehensive insights into the volatile characteristics during the industrial processing of ESYL and promote our understanding of the aroma formation in steamed green teas. © 2024 Society of Chemical Industry.
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This meta-analysis evaluates the efficacy and safety of non-surgical treatments for diabetic foot ulcers and infections. After a rigorous literature review, seven studies were selected for detailed analysis. The findings demonstrate that non-surgical treatments significantly reduce wound infection rates (standardized mean difference [SMD] = -15.15, 95% confidence interval [CI]: [-19.05, -11.25], p < 0.01) compared to surgical methods. Ulcer healing rates were found to be comparable between non-surgical and surgical approaches (SMD = 0.07, 95% CI: [-0.38, 0.51], p = 0.15). Importantly, the rate of amputations within 6 months post-treatment was significantly lower in the non-surgical group (risk ratio [RR] = 0.19, 95% CI: [0.09, 0.41], p < 0.01). Additionally, a lower mortality rate was observed in patients treated non-surgically (RR = 0.28, 95% CI: [0.13, 0.59], p < 0.01). These results affirm the effectiveness and safety of non-surgical interventions in managing diabetic foot ulcers, suggesting that they should be considered a viable option in diabetic foot care.