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1.
J Asian Nat Prod Res ; : 1-10, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38996034

RESUMEN

Three new diterpenoid alkaloids (1, 2, 3) and seventeen known (4-20) compounds were isolated from the whole plant of Delphinium sherriffii Munz (Ranunculaceae). Their structures were elucidated by various spectroscopic analyses, including IR, HR-ESI-MS, 1D and 2D NMR spectra. All compounds were evaluated for the inhibitory activity of Sf9 cells and compound 5 exhibited the strongest cytotoxicity (IC50 = 8.97 µM) against Sf9 cell line.

2.
Phytochemistry ; 225: 114186, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38878944

RESUMEN

The ethanol extract of the whole plant of Delphinium trichophorum Franch was subjected to a phytochemical study, leading to the isolation of ten unprecedented diterpenoid alkaloids, including nine delnudine-type C20-diterpenoid alkaloids named trichophodines A-I and one kusnezoline-type C20-diterpenoid alkaloid named trichophozine A. Additionally, seven known compounds were also identified. Their structures were elucidated on the basis of extensive spectroscopic analysis, including HSQC, HMBC, 1H-1H COSY, NOESY and X-ray crystallographic analysis. Most isolated compounds were screened for inhibitory activities against LPS-induced NO production in RAW 264.7 macrophage cells and acetylcholinesterase inhibitory effects. Guan-fu base V exhibited potent inhibitory activity against acetylcholinesterase, demonstrating an inhibitory rate of 53.81% at a concentration of 40 µM.


Asunto(s)
Alcaloides , Inhibidores de la Colinesterasa , Delphinium , Diterpenos , Delphinium/química , Ratones , Diterpenos/química , Diterpenos/farmacología , Diterpenos/aislamiento & purificación , Animales , Células RAW 264.7 , Alcaloides/química , Alcaloides/farmacología , Alcaloides/aislamiento & purificación , Estructura Molecular , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/aislamiento & purificación , Lipopolisacáridos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Acetilcolinesterasa/metabolismo , Acetilcolinesterasa/efectos de los fármacos , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga
3.
Muscle Nerve ; 70(2): 210-216, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38828855

RESUMEN

INTRODUCTION/AIMS: The current diagnosis of ulnar neuropathy at the elbow (UNE) relies mainly on the clinical presentation and nerve electrodiagnostic (EDX) testing, which can be uncomfortable and yield false negatives. The aim of this study was to investigate the diagnostic value of conventional ultrasound, shear wave elastography (SWE), and superb microvascular imaging (SMI) in diagnosing UNE. METHODS: We enrolled 40 patients (48 elbows) with UNE and 48 healthy volunteers (48 elbows). The patients were categorized as having mild, moderate or severe UNE based on the findings of EDX testing. The cross-sectional area (CSA) was measured using conventional ultrasound. Ulnar nerve (UN) shear wave velocity (SWV) and SMI were performed in a longitudinal plane. RESULTS: Based on the EDX findings, UNE severity was graded as mild in 4, moderate in 10, and severe in 34. The patient group showed increased ulnar nerve CSA and stiffness at the site of maximal enlargement (CSA mean at the site of max enlargement [CSAmax] and SWV mean at the site of max enlargement [SWVmax]), ulnar nerve CSA ratio, and stiffness ratio (elbow-to-upper arm), compared with the control group (p < .001). Furthermore, the severe UNE group showed higher ulnar nerve CSAmax and SWVmax compared with the mild and moderate UNE groups (p < .001). The cutoff values for diagnosis of UNE were 9.5 mm2 for CSAmax, 3.06 m/s for SWVmax, 2.00 for CSA ratio, 1.36 for stiffness ratio, and grade 1 for SMI. DISCUSSION: Our findings suggest that SWE and SMI are valuable diagnostic tools for the diagnosis and assessment of severity of UNE.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Codo , Nervio Cubital , Neuropatías Cubitales , Ultrasonografía , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Diagnóstico por Imagen de Elasticidad/métodos , Neuropatías Cubitales/diagnóstico por imagen , Neuropatías Cubitales/fisiopatología , Codo/diagnóstico por imagen , Ultrasonografía/métodos , Anciano , Nervio Cubital/diagnóstico por imagen , Nervio Cubital/fisiopatología , Microvasos/diagnóstico por imagen , Electrodiagnóstico/métodos
4.
Artículo en Inglés | MEDLINE | ID: mdl-38715377

RESUMEN

INTRODUCTION: Polycystic ovary syndrome (PCOS) is associated with a wide range of unfavorable cardiometabolic risk factors, including obesity, hypertension, insulin resistance, impaired glucose metabolism, dyslipidemia, and metabolic syndrome. Compared with women with regular menstrual cycles, women with a history of irregular menstrual periods have an increased unfavorable cardiometabolic risk. Recently, the association between the severity of oligomenorrhea and hyperinsulinemia and insulin resistance has been demonstrated. However, evidence linking the severity of menstrual cyclicity with cardiometabolic risk in PCOS women is scarce. MATERIAL AND METHODS: This work was a prospective cross-sectional study. A total of 154 women diagnosed with PCOS by the Rotterdam criteria were recruited from July 2021 to September 2022. PCOS women with eumenorrheic (eumeno group), oligomenorrhea (oligo group), and amenorrhea (ameno group) underwent history and physical examination, gonadal steroid hormone measurement, lipid profile, oral glucose tolerance test, and homeostasis model assessment of insulin resistance. RESULTS: A trend toward an increase in unfavorable cardiometabolic risk markers including obesity, hypertension, prevalence of insulin resistance, prediabetes, dyslipidemia, and metabolic syndrome was observed in the ameno group (n = 57) as compared with the eumeno (n = 24) or oligo group (n = 73). A higher prevalence of insulin resistance (odds ratio [OR]: 3.02; 95% confidence interval [CI]: 1.03-8.81) and prediabetes (OR: 3.94; 95% CI: 1.01-15.40) was observed in the ameno group than in the eumeno group, and a higher proportion of dyslipidemia (OR: 2.44; 95% CI: 1.16-5.15) was observed in the ameno group than in the oligo group in the binary logistic regression analysis after adjusting for confounding factors. CONCLUSIONS: PCOS women with amenorrhea show a higher prevalence of insulin resistance, prediabetes, and dyslipidemia compared with those with oligomenorrhea or eumenorrhea. The severity of menstrual dysfunction could be used as a readily obtainable marker for the identification of PCOS women at greatest risk of cardiometabolic diseases.

5.
Bioact Mater ; 39: 14-24, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38783926

RESUMEN

Tumor-promoting niche after incomplete surgery resection (SR) can lead to more aggressive local progression and distant metastasis with augmented angiogenesis-immunosuppressive tumor microenvironment (TME). Herein, elevated neutrophil extracellular traps (NETs) and cancer-associated neurotransmitters (CANTs, e.g., catecholamines) are firstly identified as two of the dominant inducements. Further, an injectable fibrin-alginate hydrogel with high tissue adhesion has been constructed to specifically co-deliver NETs inhibitor (DNase I)-encapsulated PLGA nanoparticles and an unselective ß-adrenergic receptor blocker (propranolol). The two components (i.e., fibrin and alginate) can respond to two triggers (thrombin and Ca2+, respectively) in postoperative bleeding to gelate, shaping into an interpenetrating network (IPN) featuring high strength. The continuous release of DNase I and PR can wreck NETs and antagonize catecholamines to decrease microvessel density, blockade myeloid-derived suppressor cells, secrete various proinflammatory cytokines, potentiate natural killer cell function and hamper cytotoxic T cell exhaustion. The reprogrammed TME significantly suppress locally residual and distant tumors, induce strong immune memory effects and thus inhibit lung metastasis. Thus, targetedly degrading NETs and blocking CANTs enabled by this in-situ IPN-based hydrogel drug depot provides a simple and efficient approach against SR-induced cancer recurrence and metastasis.

6.
Eur J Radiol ; 176: 111512, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38788609

RESUMEN

OBJECTIVE: To evaluate the effectiveness of a decision tree that integrates conventional ultrasound (CUS) with two different strain imaging (SI) techniques for diagnosing breast lesions, and to analyze the factors contributing to false negative (FN) and false positive (FP) in the decision tree's outcomes. MATERIALS AND METHODS: Imaging and clinical data of 796 cases in the training set and 351 cases in the validation set were prospectively collected. A decision tree model that combines two types of SI and CUS was constructed, and its diagnostic performance was analyzed. Univariate analysis and multivariate analysis were applied to identify independent risk factors associated with FP and FN results of the decision tree model. RESULTS: Size, shape, margin, vascularity, the types of internal calcifications, EI score and VTI pattern were found to be significantly independently associated with the diagnosis of benign and malignant breast lesions. Therefore, size, shape, margin, vascularity, EI score and VTI pattern were used to construct decision tree models. The Tree (EI+VTI) model had the highest AUC. Both in the training and validation groups, the AUC of Tree (EI+VTI) was significantly higher compared with that of EI, VTI, and BI-RADS (all, P < 0.05). Orientation, posterior acoustic features and the types of internal calcifications were significantly positively associated with misdiagnosis results of Tree (EI+VTI) in evaluation of breast lesions (all P < 0.05). CONCLUSION: The diagnostic model based on a decision tree that integrates two distinct types of SI with CUS enhances the diagnostic accuracy of each method when used individually. This integration lowers the misdiagnosis rate, potentially assisting radiologists in more effective lesion assessments. When applying the decision tree model, attention should be paid to the orientation, posterior acoustic features, and the types of internal calcifications of the lesions.


Asunto(s)
Neoplasias de la Mama , Árboles de Decisión , Errores Diagnósticos , Ultrasonografía Mamaria , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Persona de Mediana Edad , Ultrasonografía Mamaria/métodos , Adulto , Anciano , Sensibilidad y Especificidad , Reproducibilidad de los Resultados , Estudios Prospectivos
7.
Nat Prod Res ; : 1-7, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38771014

RESUMEN

An undescribed dammarane triterpenoid saponin Cypaliuruside F was isolated from the leaves of Cyclocarya paliurus in our preliminary study. The MTT assay, flow cytometry, cell scratch, and DAPI staining were used to detect the antitumor effects of Cypaliuruside F on HepG2 cells. Subsequently, network pharmacology and molecular docking analysis were used to analyse the key targets of Cypaliuruside F against HCC. In addition, a Western blot was performed to determine the effects of Cypaliuruside F on the expression of key proteins in HepG2 cells. The experimental results indicated that the damarane triterpenoid saponin Cypaliuruside F from Cyclocarya paliurus inhibits the proliferation of HepG2 cells by inducing apoptosis and cell cycle arrest. These changes may promote the apoptosis of HepG2 cells by inhibiting the expression of mTOR, STAT3, and Bcl-2 while activating Bax.

8.
Phytochemistry ; 223: 114115, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38710377

RESUMEN

A total of twenty-two diterpenoid alkaloids, including ten unprecedented ones, namely refractines C-L, were isolated from the roots of Aconitum refractum (Finet et Gagnep.) Hand.-Mazz. Refractine C was the first example of a natural diterpenoid alkaloid wherein C-19 is linked to N position by an oxaziridine ring. Refractine L was a rare glycosidic diterpenoid alkaloid with fructofuranoside. Most of the isolated compounds obtained from a previous study were screened for their anti-inflammatory and myocardial protective activities. The autophagy-inducing effects of some of these compounds on RAW 264.7 cells were evaluated by assessing the expression of microtubule-associated protein 1 light chain 3 (LC3-II/LC3-I). Results revealed that some compounds exerted varying levels of inhibitory effects on the proliferative activity of RAW 264.7 cells.


Asunto(s)
Aconitum , Alcaloides , Autofagia , Diterpenos , Aconitum/química , Ratones , Animales , Autofagia/efectos de los fármacos , Células RAW 264.7 , Alcaloides/farmacología , Alcaloides/aislamiento & purificación , Alcaloides/química , Diterpenos/farmacología , Diterpenos/química , Diterpenos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Estructura Molecular , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Raíces de Plantas/química
9.
J Med Chem ; 67(8): 6585-6609, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38598362

RESUMEN

G0775, an arylomycin-type SPase I inhibitor that is being evaluated in a preclinical study, exhibited potent antibacterial activities against some Gram-negative bacteria but meanwhile suffered defects such as a narrow antibacterial spectrum and poor pharmacokinetic properties. Herein, systematic structural modifications were carried out, including optimization of the macrocyclic skeleton, warheads, and lipophilic regions. The optimization culminated in the discovery of 138f, which showed more potent activity and a broader spectrum against clinically isolated carbapenem-resistant Gram-negative bacteria, especially against Acinetobacter baumannii and Pseudomonas aeruginosa. 162, the free amine of 138f, exhibited an excellent pharmacokinetic profile in rats. In a neutropenic mouse thigh model of infection with multidrug-resistant P. aeruginosa, the potent in vivo antibacterial efficacy of 162 was confirmed and superior to that of G0775 (3.5-log decrease vs 1.1-log decrease in colony-forming unit (CFU)). These results support 162 as a potential antimicrobial agent for further research.


Asunto(s)
Antibacterianos , Diseño de Fármacos , Farmacorresistencia Bacteriana Múltiple , Bacterias Gramnegativas , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/uso terapéutico , Animales , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Ratones , Relación Estructura-Actividad , Pseudomonas aeruginosa/efectos de los fármacos , Ratas , Acinetobacter baumannii/efectos de los fármacos , Masculino
10.
Heliyon ; 10(7): e28084, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38601687

RESUMEN

The ceRNA network, consisting of both noncoding RNA and protein-coding RNA, governs the occurrence, progression, metastasis, and infiltration of lung adenocarcinoma. Signatures comprising multiple genes can effectively determine survival stratification and prognosis of patients with lung adenocarcinoma. To explore the mechanisms of lung adenocarcinoma progression and identify potential biological targets, we carried out systematic bioinformatics analyses of the genetic profiles of lung adenocarcinoma, such as weighted gene co-expression network analysis (WGCNA), differential expression (DE) assessment, univariate and multivariate Cox proportional hazard regression models, ceRNA modulatory networks generated using the ENCORI and miRcode databases, nomogram models, ROC curve assessment, and Kaplan-Meier survival curve analysis. The ceRNA network encompassed 37 nodes, comprising 12 mRNAs, 22 lncRNAs, and three miRNAs. Simultaneously, we performed integration analysis using the 12 genes from the ceRNA network. Our findings revealed that the signature established by these 12 genes serves as an adverse element in lung adenocarcinoma, contributing to unfavorable patient prognosis. To ensure the credibility of our results, we used in vitro experiments for further verification. In conclusion, our study delved into the potential mechanisms underlying lung adenocarcinoma via the ceRNA regulatory network, specifically focusing on the PIF1 and has-miR-125a-5p axis. Additionally, a signature comprising 12 genes was identified as a biomarker related to the prognosis of lung adenocarcinoma.

11.
Bioorg Chem ; 146: 107297, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38503027

RESUMEN

In our previous study, a screening of a variety of lycotonine-type diterpenoid alkaloids were screened for cardiotonic activity revealed that lycoctonine had moderate cardiac effect. In this study, a series of structurally diverse of lycoctonine were synthesized by modifying on B-ring, D-ring, E-ring, F-ring, N-atom or salt formation on lycoctonine skeleton. We evaluated the cardiotonic activity of the derivatives by isolated frog heart, aiming to identify some compounds with significantly enhanced cardiac effects, among which compound 27 with a N-isobutyl group emerged as the most promising cardiotonic candidate. Furthermore, the cardiotonic mechanism of compound 27 was preliminarily investigated. The result suggested that the cardiotonic effect of compound 27 is related to calcium channels. Patch clamp technique confirmed that the compound 27 had inhibitory effects on CaV1.2 and CaV3.2, with inhibition rates of 78.52 % ± 2.26 % and 79.05 % ± 1.59 % at the concentration of 50 µM, respectively. Subsequently, the protective effect of 27 on H9c2 cells injury induced by cobalt chloride was tested. In addition, compound 27 can alleviate CoCl2-induced myocardial injury by alleviating calcium overload. These findings suggest that compound 27 was a new structural derived from lycoctonine, which may serve as a new lead compound for the treatment of heart failure.


Asunto(s)
Aconitina/análogos & derivados , Alcaloides , Cardiotónicos , Cardiotónicos/farmacología , Aconitina/química , Alcaloides/farmacología , Alcaloides/química , Canales de Calcio , Calcio
12.
Br J Radiol ; 97(1153): 159-167, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38263832

RESUMEN

OBJECTIVES: To build a predictive model for central lymph node metastasis (CLNM) in unifocal papillary thyroid carcinoma (UPTC) using a combination of clinical features and multimodal ultrasound (MUS). METHODS: This retrospective study, included 390 UPTC patients who underwent MUS between January 2017 and October 2022 and were divided into a training cohort (n = 300) and a validation cohort (n = 90) based on a cut-off date of June 2022. Independent indicators for constructing the predictive nomogram models were identified using multivariate regression analysis. The diagnostic yield of the 3 predictive models was also assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: Both clinical factors (age, diameter) and MUS findings (microcalcification, virtual touch imaging score, maximal value of virtual touch tissue imaging and quantification) were significantly associated with the presence of CLNM in the training cohort (all P < .05). A predictive model (MUS + Clin), incorporating both clinical and MUS characteristics, demonstrated favourable diagnostic accuracy in both the training cohort (AUC = 0.80) and the validation cohort (AUC = 0.77). The MUS + Clin model exhibited superior predictive performance in terms of AUCs over the other models (training cohort 0.80 vs 0.72, validation cohort 0.77 vs 0.65, P < .01). In the validation cohort, the MUS + Clin model exhibited higher sensitivity compared to the CLNM model for ultrasound diagnosis (81.2% vs 21.6%, P < .001), while maintaining comparable specificity to the Clin model alone (62.3% vs 47.2%, P = .06). The MUS + Clin model demonstrated good calibration and clinical utility across both cohorts. CONCLUSION: Our nomogram combining non-invasive features, including MUS and clinical characteristics, could be a reliable preoperative tool to predict CLNM treatment of UPTC. ADVANCES IN KNOWLEDGE: Our study established a nomogram based on MUS and clinical features for predicting CLNM in UPTC, facilitating informed preoperative clinical management and diagnosis.


Asunto(s)
Nomogramas , Neoplasias de la Tiroides , Humanos , Metástasis Linfática , Estudios Retrospectivos , Cáncer Papilar Tiroideo
13.
Chem Biodivers ; 21(6): e202301923, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38191840

RESUMEN

Two new C19-diterpenoid alkaloids of the lycoctonine-type (liangshanine A and liangshanine B) and nineteen known compounds (3-21) were isolated from the whole plant of Delphinium liangshanense W. T. Wang, and all the compounds were identified by different spectroscopic analyses, such as IR, HR-ESI-MS and NMR. All the compounds were isolated from this plant for the first time and tested for the anti-proliferation effects on MH7 A and SF9 cells to figure their anti-rheumatoid arthritis and anti-insect activity, but none of them showed remarkable activity.


Asunto(s)
Alcaloides , Delphinium , Diterpenos , Delphinium/química , Diterpenos/química , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Animales , Proliferación Celular/efectos de los fármacos , Línea Celular , Spodoptera/efectos de los fármacos , Estructura Molecular , Humanos , Conformación Molecular
14.
Ultrason Imaging ; 46(2): 121-129, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38197383

RESUMEN

To establish a predictive model incorporating conventional ultrasound, strain elastography and clinicopathological features for Ki-67 expression in small breast cancer (SBC) which defined as maximum diameter less than2 cm. In this retrospective study, 165 SBC patients from our hospital were allocated to a high Ki-67 group (n = 104) and a low Ki-67 group (n = 61). Multivariate regression analysis was performed to identify independent indicators for developing predictive models. The area under the receiver operating characteristic (AUC) curve was also determined to establish the diagnostic performance of different predictive models. The corresponding sensitivities and specificities of different models at the cutoff value were compared. Conventional ultrasound parameters (spiculated margin, absence of posterior shadowing and Adler grade 2-3), strain elastic scores and clinicopathological information (HER2 positive) were significantly correlated with high expression of Ki-67 in SBC (all p < .05). Model 2, which incorporated conventional ultrasound features and strain elastic scores, yielded good diagnostic performance (AUC = 0.774) with better sensitivity than model 1, which only incorporated ultrasound characteristics (78.85%vs. 55.77%, p = .000), with specificities of 77.05% and 62.30% (p = .035), respectively. Model 3, which incorporated conventional ultrasound, strain elastography and clinicopathological features, yielded better performance (AUC = 0.853) than model 1 (AUC = 0.694) and model 2 (AUC = 0.774), and the specificity was higher than model 1 (86.89% vs. 77.05%, p = .001). The predictive model combining conventional ultrasound, strain elastic scores and clinicopathological features could improve the predictive performance of Ki-67 expression in SBC.


Asunto(s)
Neoplasias de la Mama , Diagnóstico por Imagen de Elasticidad , Femenino , Humanos , Neoplasias de la Mama/diagnóstico por imagen , Antígeno Ki-67 , Ultrasonografía Mamaria , Estudios Retrospectivos
15.
Gene ; 896: 148035, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38013128

RESUMEN

PURPOSE: Vascular calcification is a frequently occurring complication of end-stage renal disease (ESRD). This study focused on the significance of long non-coding RNA Fas cell surface death receptor-antisense 1(lncRNA FAS-AS1) in ESRD-related vascular calcification aiming to explore a potential biomarker for the detection. METHODS: The study enrolled 65 healthy individuals, 79 ESRD patients (48 patients with vascular calcification), and 93 early-stage (I-IV) chronic kidney disease (CKD) patients. The expression of FAS-AS1 in serum was evaluated by real-time quantitative polymerase chain reaction (PCR). The diagnostic potential of FAS-AS1 was assessed in discriminating ESRD patients, vascular calcification, and the severity of vascular calcification. In vitro, the vascular smooth muscle cells (VSMCs) were treated with a hyperphosphatemia medium to evaluate the effect of FAS-AS1 on VSMCs calcification. RESULTS: Elevated serum FAS-AS1 was observed in ESRD patients, which could discriminate from healthy individuals and early-stage CKD patients. FAS-AS1 was associated with the development of ESRD and the occurrence of vascular calcification. FAS-AS1 was also upregulated in vascular calcification patients, especially the patients with severe calcification, which showed diagnostic significance in evaluating vascular calcification degrees. Calcified VSMCs showed significantly increased levels of Ca2+, reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6), which was attenuated by silencing FAS-AS1. CONCLUSIONS: FAS-AS1 discriminated ERSD patients and was associated with the occurrence of vascular calcification. The knockdown of FAS-AS1 suppressed hyperphosphatemia-induced vascular calcification via alleviating oxidative stress and inflammation.


Asunto(s)
Hiperfosfatemia , Fallo Renal Crónico , ARN Largo no Codificante , Insuficiencia Renal Crónica , Calcificación Vascular , Humanos , Hiperfosfatemia/complicaciones , Hiperfosfatemia/metabolismo , Hiperfosfatemia/patología , Inflamación/genética , Inflamación/metabolismo , Fallo Renal Crónico/genética , Miocitos del Músculo Liso/metabolismo , Estrés Oxidativo/genética , Insuficiencia Renal Crónica/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Calcificación Vascular/genética , Calcificación Vascular/metabolismo
16.
Bioorg Chem ; 143: 107025, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38103332

RESUMEN

Two novel naturally occurring [4 + 2] Diels-Alder cycloaddition ergosteroids (1 and 2), three undescribed oxidized ergosteroids (3-5), and eleven known analogs (6-16) were isolated from Penicillium herquei. Compounds 1 and 2 represent the first reported cycloadducts of a steroid with 1,4,6-trimethyl-1,6-dihydropyridine-2,5-dione or 4,6-dimethyl-1,6-dihydropyridine-2,5-dione to date. Compound 3 is the C-15 epimer of (22E,24R)-9α,11ß-dihydroxyergosta-4,6,8(14),22-tetraen-3-one (14). The chemical structures of these compounds were elucidated through widespread spectroscopic analyses, mainly including HRESIMS and 1D and 2D NMR data, calculated 13C NMR-DP4+ analysis, and electronic circular dichroism (ECD) data analyses. Biological evaluations of Compounds 1-16 revealed that 3, 9-11, and 15 inhibited the production of NO in LPS-induced RAW264.7 cells with an IC50 value from 7.37 ± 0.69 to 38.9 ± 2.25 µM (the positive control dexamethasone IC50: 9.54 ± 0.71 µM). In addition, Compound 3 exhibited a potent inhibitory effect on the secretion of the proinflammatory cytokines TNF-α and IL-6, the transcription level of the proinflammatory macrophage markers TNF-α, and the expression of the iNOS protein.


Asunto(s)
Dihidropiridinas , Penicillium , Reacción de Cicloadición , Factor de Necrosis Tumoral alfa , Penicillium/química , Espectroscopía de Resonancia Magnética , Estructura Molecular
17.
Chem Biodivers ; 21(2): e202301761, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38117633

RESUMEN

Natural products and their derivatives are a precious treasure in the pursuit of potent anti-inflammatory drugs. In this work, we measured the toxicity of 78 LA derivatives at 20 µM using MTT, then we evaluated the NO release of compounds without obvious toxicity in LPS-induced RAW.264.7 by Griess reagent, we identified three compounds, namely compounds 6, 19, 70, which exhibited promising anti-inflammatory potential. These compounds exhibited IC50 values of 10.34±2.05 µM, 18.18±4.80 µM and 15.66±0.88 µM. In addition, through ELISA kits, compounds 6, 19, 70 significantly reduce the production of inflammatory factors (TNF-α, IL-6, IL-1ß). Real-time PCR and western blot analysis showed that compounds 6, 19, 70 inhibited the mRNA and protein expression of iNOS and COX-2. Notably, compound 6 exhibited the most potent inhibitory activity. In vitro, it inhibits LPS-induced phosphorylation of NF-κB p65, IκBα, ERK1/2, JNK, and p38 MAPKs in RAW264.7 cells. In vivo, compound 6 potently inhibits the secretion of inflammatory mediators and neutrophil activation in ALI mice. Our findings suggest that compound 6 may be a potential anti-inflammatory drug.


Asunto(s)
Aconitina/análogos & derivados , Lipopolisacáridos , FN-kappa B , Animales , Ratones , FN-kappa B/metabolismo , Lipopolisacáridos/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Células RAW 264.7 , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo
18.
Nat Prod Res ; 38(1): 78-84, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-35876238

RESUMEN

Two new compounds geobomlin A (1) and geobomlin B (2) were isolated from the roots of Stachys geobombycis C. Y. Wu. Structural determinations were established principally by two-dimensional NMR and MS data analyses. Geobomlin B showed moderate inhibitory activity against α-glucosidase with IC50 = 248.77 µM. We have also determined the mechanism by which geobomlin B elicit its inhibitory effect on α-glucosidase, for which we have established a competitive inhibition mode. Docking studies confirmed our results on geobomlin B α-glucosidase inhibitory properties.


Asunto(s)
Glicósidos , Stachys , Glicósidos/química , Stachys/química , alfa-Glucosidasas/metabolismo , Espectroscopía de Resonancia Magnética , Raíces de Plantas/química , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Simulación del Acoplamiento Molecular , Estructura Molecular
19.
Artif Intell Med ; 146: 102699, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38042598

RESUMEN

Early detection and accurate identification of thyroid nodules are the major challenges in controlling and treating thyroid cancer that can be difficult even for expert physicians. Currently, many computer-aided diagnosis (CAD) systems have been developed to assist this clinical process. However, most of these systems are unable to well capture geometrically diverse thyroid nodule representations from ultrasound images with subtle and various characteristic differences, resulting in suboptimal diagnosis and lack of clinical interpretability, which may affect their credibility in the clinic. In this context, a novel end-to-end network equipped with a deformable attention network and a distillation-driven interaction aggregation module (DIAM) is developed for thyroid nodule identification. The deformable attention network learns to identify discriminative features of nodules under the guidance of the deformable attention module (DAM) and an online class activation mapping (CAM) mechanism and suggests the location of diagnostic features to provide interpretable predictions. DIAM is designed to take advantage of the complementarities of adjacent layers, thus enhancing the representation capabilities of aggregated features; driven by an efficient self-distillation mechanism, the identification process is complemented with more multi-scale semantic information to calibrate the diagnosis results. Experimental results on a large dataset with varying nodule appearances show that the proposed network can achieve competitive performance in nodule diagnosis and provide interpretability suitable for clinical needs.


Asunto(s)
Nódulo Tiroideo , Humanos , Nódulo Tiroideo/diagnóstico por imagen , Destilación , Diagnóstico por Computador/métodos , Ultrasonografía/métodos
20.
Curr Med Sci ; 43(6): 1075-1083, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38041791

RESUMEN

Endometrial receptivity is an important factor that influences embryo implantation. Thus, it is important to identify an applicable approach to improve endometrial receptivity in women undergoing assisted reproductive technology. Recently, growing evidence has indicated that intrauterine platelet-rich plasma (PRP) infusion is an effective method to obtain a satisfactory reproductive outcome by increasing endometrial thickness and improving endometrial receptivity. Therefore, the present review aims to outline the possible mechanisms of PRP on endometrial receptivity and summarize the present literature on the effects of PRP therapy in improving endometrial receptivity.


Asunto(s)
Transferencia de Embrión , Plasma Rico en Plaquetas , Humanos , Femenino , Implantación del Embrión , Endometrio , Técnicas Reproductivas Asistidas
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