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1.
Fitoterapia ; 176: 105976, 2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38685511

RESUMEN

Phytochemical research on an extract of Notopterygium incisum yielded fifteen compounds (1-15), including four previously undescribed compounds (10-13). The structures of the unreported compounds were elucidated by spectroscopic and spectrometric data analysis such as 1D and 2D NMR, IR and HR-ESI-MS. Compounds 1-5 and 10-14 were isolated from N. incisum for the first time. 7S⁎,8R⁎-Phenethyl-(7-methoxy-8-isoeugenol)-ferulate (10), 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11), 7S⁎,8R⁎-benzyl-(7-methoxy-8-isoeugenol)-ferulate (12) and p-hydroxyphenethyl-(4-benzoy-3-methoxy)-cinnamate (13) are the undescribed ferulic acid derivatives. Additionly, the anti-neuroinflammatory effects of compounds were evaluated in lipopolysaccharide (LPS)-induced BV2 cells. The pharmacological results showed that 6ß,10ß-epoxy-4α-hydroxy-guaiane (6), teuclatriol (7) and 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11) inhibited the production and expression of nitric oxide (NO) in the LPS-induced BV2 cells in a concentration-dependent manner. Acorusnol (4), teucladiol (9), 7S⁎,8R⁎-benzyl-(7-methoxy-8-isoeugenol)-ferulate (12) and p-hydroxyphenethyl-(4-benzoy-3-methoxy)-cinnamate (13) only inhibited the release of NO at concentration of 20 µM. Moreover, 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11) reduced the level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in LPS-stimulated BV2 cells. The results demonstrated 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11) could be a potential anti-neuroinflammatory agent and is worthy of further study.

2.
J Ethnopharmacol ; 330: 118218, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38677570

RESUMEN

ETHNOPHARMACOLOGY RELEVANCE: Zanthoxylum bungeanum Maxim. (Z. bungeanum), a member of the Rutaceae family, has a rich history of traditional use in Asia for treating arthritis and toothache conditions. As characteristic chemical components, numerous kinds of alkaloids have been extracted from plants and their diverse biological activities have been reported. However, research on the isoquinoline alkaloid, a specific type of alkaloids, in Z. bungeanum was scarce. AIM OF THE STUDY: The study aimed to isolate a novel isoquinoline alkaloid from Z. bungeanum and explore its pharmacological activity in vitro and analgesic activity in vivo. MATERIALS AND METHODS: Isoquinoline alkaloid isolation and identification from Z. bungeanum were conducted using chromatographic and spectroscopic methods. The whole-cell patch-clamp technique was applied to assess its impact on neuronal excitability, and endogenous voltage-gated potassium (Kv) and sodium (Nav) currents in acutely isolated mouse small-diameter dorsal root ganglion (DRG) neurons. Its inhibitory impacts on channels were further validated with HEK293 cells stably expressing Nav1.7 and Nav1.8, and Chinese hamster ovary (CHO) cells transiently expressing Kv2.1. The formalin inflammatory pain model was utilized to evaluate the potential analgesic activity in vivo. RESULTS: A novel isoquinoline alkaloid named HJ-69 (N-13-(3-methoxyprop-1-yl)rutaecarpine) was isolated and identified from Z. bungeanum for the first time. HJ-69 significantly suppressed the firing frequency and amplitudes of action potentials in DRG neurons. Consistently, it state-dependently inhibited endogenous Nav currents of DRG neurons, with half maximal inhibitory concentration (IC50) values of 13.06 ± 2.06 µM and 30.19 ± 2.07 µM for the inactivated and resting states, respectively. HJ-69 significantly suppressed potassium currents in DRG neurons, which notably inhibited the delayed rectifier potassium (IK) currents (IC50 = 6.95 ± 1.29 µM) and slightly affected the transient outward potassium (IA) currents (IC50 = 523.50 ± 39.16 µM). Furtherly, HJ-69 exhibited similar potencies on heterologously expressed Nav1.7, Nav1.8, and Kv2.1 channels, which correspondingly represent the main components in neurons. Notably, intraperitoneal administration of 30 mg/kg and 100 mg/kg HJ-69 significantly alleviated pain behaviors in the mouse inflammatory pain model induced by formalin. CONCLUSION: The study concluded that HJ-69 is a novel and active isoquinoline alkaloid, and the inhibition of Nav and Kv channels contributes to its analgesic activity. HJ-69 may be a promising prototype for future analgesic drug discovery based on the isoquinoline alkaloid.


Asunto(s)
Analgésicos , Ganglios Espinales , Dolor , Zanthoxylum , Animales , Zanthoxylum/química , Humanos , Células HEK293 , Analgésicos/farmacología , Analgésicos/química , Analgésicos/aislamiento & purificación , Analgésicos/uso terapéutico , Ganglios Espinales/efectos de los fármacos , Ganglios Espinales/metabolismo , Ratones , Masculino , Dolor/tratamiento farmacológico , Isoquinolinas/farmacología , Isoquinolinas/aislamiento & purificación , Isoquinolinas/química , Alcaloides/farmacología , Alcaloides/aislamiento & purificación , Alcaloides/química , Alcaloides/uso terapéutico , Bloqueadores de los Canales de Potasio/farmacología , Canal de Sodio Activado por Voltaje NAV1.7/metabolismo , Inflamación/tratamiento farmacológico , Bloqueadores del Canal de Sodio Activado por Voltaje/farmacología , Bloqueadores del Canal de Sodio Activado por Voltaje/aislamiento & purificación , Canales de Potasio con Entrada de Voltaje/metabolismo , Canales de Potasio con Entrada de Voltaje/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/química , Ratones Endogámicos C57BL , Cricetulus
3.
Microorganisms ; 11(12)2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-38138147

RESUMEN

This study investigated the effects of single Fenton and Fenton and UV combined processes on the cracking degree of anaerobic sludge under the same conditions. The optimal experimental conditions were obtained by repeated determination of Fe2+ dosage, H2O2 dosage and reaction time, so as to achieve the maximum cracking of sludge. In addition, this study applied three-dimensional fluorescence spectrum analysis technology to analyze the organic matter leached from the treated sludge, and different regions of the three-dimensional fluorescence spectra were analyzed and compared for each treatment condition. Repeated experiments showed that the optimal conditions for Fenton are a pH of 3, reaction time of 40 min, 1.4 g/L of Fe2+ and 9 g/L of H2O2. The Fenton process cracking yielded a protein concentration of 0.66 mg/L and sCOD of 5489 mg/L, and the UV-Fenton pretreatment yielded a protein concentration of 0.74 mg/L and sCOD of 5856 mg/L. The sludge particle size was reduced from the original 54.52 mm to 40.30 mm and 36.37 mm, respectively. In addition to these parameters, it was also demonstrated that the Fenton process has a strong cracking effect on sludge by indicators such as the SEM and sludge water content and that UV irradiation can play a role in assisting and helping sludge cracking.

4.
Phytochemistry ; 214: 113824, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37597719

RESUMEN

Eight previously unreported sesquiterpene coumarins, namely (+)- and (-)-ferulasinkian A (1), (-)-fukanefuromarin M (2), (±)-ferulasinkian C (3), (±)-ferulasinkian D (4), ferulasinkian E (5), ferulasinkian F (7), and ferulasinkian G (8), together with two known compounds, (+)-fukanefuromarin M (2) and 7-hydroxyferprenin (6), have been isolated from the roots of Ferula sinkiangensis (Umbelliferae). The structures of all compounds were elucidated by spectroscopic analysis, along with ECD calculations and optical rotation calculations. Compounds 1-6 are dimers consisting of a chain sesquiterpene and a coumarin with an oxygen-containing six-membered ring connected from coumarin C-3 and C-4. Currently, there are only seven such structures reported in the genus Ferula, and their absolute configurations have not yet been determined. Compounds 7-8 are sesquiterpene coumarin derivatives with a chain sesquiterpene connected with coumarin C-4. In the present study, the chiral separation of compounds (±)-1 and (±)-2 was successfully carried out, and the absolute configurations of compounds (±)-1, (±)-2, 5, 7 and 8 were determined. The isolates were evaluated for their cytotoxic activity against human pancreatic cancer cell lines including CFPAC-1, PANC-1, CAPAN-2 and SW 1990. Compounds (+)-1, (-)-1 and 7 exhibited potent cytotoxicity against pancreatic cancer cells with IC50 values ranging from 4.57 ± 0.94 to 14.01 ± 1.03 µM. Furthermore, the primary mechanistic study of (-)-1 demonstrated that it could induce apoptosis in CFPAC-1 cells.

5.
Phytochemistry ; 211: 113704, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37146703

RESUMEN

Zanthoxylum armatum DC. is an important medicinal plant, and its pericarps are commonly used as a natural spice in Asian countries. In this study, fifteen alkylamides were isolated and elucidated from the pericarps of Z. armatum, including five undescribed alkylamides (1-5) and ten known compounds (6-15). The molecular structures of all compounds were elucidated by 1D and 2D NMR spectroscopic analysis and mass spectrometry, among which the absolute configuration of compound 15 was determined by the Mo2(OAc)4-induced circular dichroism method. Moreover, all compounds were screened for their neuroprotective activity against H2O2-induced oxidative stress in human neuroblastoma SH-SY5Y cells for the evaluation of their neuroprotective activity. Especially, compounds 2-4 expressed potential neuroprotective activity, and further research showed that the cell viability was significantly enhanced in a concentration dependent manner when the cells were treated for 6 h. Moreover, compounds 2-4 could decrease reactive oxygen species accumulation. This paper enriched structure types of alkylamides in Zanthoxylum armatum.


Asunto(s)
Neuroblastoma , Zanthoxylum , Humanos , Zanthoxylum/química , Peróxido de Hidrógeno/farmacología , Espectrometría de Masas , Estructura Molecular
6.
BMC Cardiovasc Disord ; 22(1): 550, 2022 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-36528570

RESUMEN

PURPOSE: We evaluated quality of life (QoL) in pregnant women who underwent transthoracic echocardiography-guided percutaneous closure of atrial septal defect (ASD). METHODS: A total of 45 pregnant women underwent transthoracic echocardiography-guided percutaneous closure of ASD. We assessed QoL using the 36-Item Short Form Survey (SF-36) and compared results between pre- and post-procedure patients, as well as between those with ASD and healthy women in their second and third trimesters of pregnancy. RESULTS: All patients showed improved right ventricular function and were classified as Class I, post-procedure. Mean SF-36 scores of the post-procedure group were better on all sub-scales than those of the pre-procedure group (p < 0.05), with the exception of role-emotional and mental health. Mean SF-36 scores for the pre-procedure group were also lower on all sub-scales than those of healthy pregnant controls (p < 0.05), with the exception of role physical, role emotional, and mental health. There was no difference between the post-procedure group and healthy pregnant controls. In a subgroup analysis, scores were better in some dimensions (social functioning and role emotional) for post-procedure patients in the 31-40 years of age group and the group on their second or third pregnancies than those of the 20-30 years of age group and the group on their first pregnancies (p < 0.05). CONCLUSION: After closure of ASD, QoL in pregnant women was improved. In a subgroup analysis, the younger women and those on their first pregnancy performed more poorly in some dimensions (social functioning and role emotional); this suggested that these groups should receive more proactive intervention.


Limited data was available on the general quality of life (QoL) in pregnant women with atrial septal defect (ASD), even though the condition could produce anxiety over health of the pregnancy and fetus. The percutaneous closure procedure was available for ASD during pregnancy; however, pregnant women were often concerned that the required X-rays would harm the fetus. A safe and effective procedure, percutaneous closure of ASD guided by transthoracic echocardiography, was widely used for this condition. This study used the 36-Item Short Form Survey (SF-36) to assess QoL in pregnant women with ASD pre- and post-procedure and compared the results to those of healthy pregnant women at a similar stage of pregnancy. Post-procedure QoL in pregnant women with ASD was improved; however, the younger women and those on their first pregnancy performed more poorly in some dimensions (social functioning and role emotional). Our results suggested that these groups should receive more proactive intervention.


Asunto(s)
Defectos del Tabique Interatrial , Dispositivo Oclusor Septal , Embarazo , Femenino , Humanos , Adulto Joven , Adulto , Calidad de Vida , Cateterismo Cardíaco/métodos , Defectos del Tabique Interatrial/diagnóstico por imagen , Defectos del Tabique Interatrial/terapia , Ecocardiografía , Encuestas y Cuestionarios , Resultado del Tratamiento
7.
BMC Pediatr ; 22(1): 684, 2022 11 29.
Artículo en Inglés | MEDLINE | ID: mdl-36443708

RESUMEN

BACKGROUND: This study aimed to evaluate and compare two surgical approaches to repair ventricular septal defect (VSD) with patent ductus arteriosus (PDA) and to explore the patients' health-related quality of life (HRQoL). METHODS: We conducted a retrospective study of all patients who had surgical repair of VSD and PDA between 2013 and 2015 using the right subaxillary approach (group A) or the median sternotomy incision (group B). The outcomes of both techniques were compared. Paediatric QoL Inventory 4.0 scale was applied to assess patients' HRQoL in the 6th postoperative year. Multiple linear regression analysis was performed to explore factors associated with higher HRQoL scores. RESULTS: A total of 128 patients were included (group A, n = 70 and group B, n = 58). Patients in group A were older and heavier than patients in group B. In group B, the diameters of VSD and PDA were larger and the pulmonary artery pressures were higher than those in group A (p < 0.001). No mortality occurred on a mean follow-up of 8.3 ± 1.2 years. Patients in group A had higher HRQoL scores than those in group B in terms of emotional and social functioning dimensions. The right subaxillary approach (OR: 3.56; 95% CI 1.65-5.46), higher parents' education level (OR: 1.62; 95% CI 0.65-2.31), and better family economic status (OR: 1.48; 95% CI 0.79-2.45) were associated with higher HRQoL scores. CONCLUSIONS: Younger and smaller patients receiving median sternotomy incisions due to large defects and pulmonary hypertension had lower HRQoL scores. The right subaxillary approach, higher parents' education level, and better family economic status were associated with higher HRQoL scores.


Asunto(s)
Conducto Arterioso Permeable , Defectos del Tabique Interventricular , Niño , Humanos , Conducto Arterioso Permeable/cirugía , Esternotomía , Calidad de Vida , Estudios Retrospectivos , Defectos del Tabique Interventricular/cirugía
8.
Molecules ; 27(21)2022 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-36364317

RESUMEN

Natural products (NPs) were a rich source of diverse bioactive molecules. Most anti-tumor agents were built on natural scaffolds. Nardostachys jatamansi DC. was an important plant used to process the traditional Chinese herbal medicines "gansong". Pancreatic cancer was the fourth most common cause of cancer-related death in the world. Hence, there was an urgent need to develop novel agents for the treatment of pancreatic cancer. In this paper, nardoguaianone L (G-6) is isolated from N. jatamansi, which inhibited SW1990 cells colony formation and cell migration, and induced cell apoptosis. Furthermore, we analyzed the differential expression proteins after treatment with G-6 in SW1990 cells by using iTRAQ/TMT-based quantitative proteomics technology, and the results showed that G-6 regulated 143 proteins' differential expression by GO annotation, including biological process, cellular component, and molecular function. Meanwhile, KEGG enrichment found that with Human T-cell leukemia virus, one infection was the most highly enhanced pathway. Furthermore, the MET/PTEN/TGF-ß pathway was identified as a significant pathway that had important biological functions, including cell migration and motility by PPI network analysis in SW1990 cells. Taken together, our study found that G-6 is a potential anti-pancreatic cancer agent with regulation of MET/PTEN/TGF-ß pathway.


Asunto(s)
Nardostachys , Neoplasias , Humanos , Apoptosis , Factor de Crecimiento Transformador beta
9.
Molecules ; 27(21)2022 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-36364344

RESUMEN

The occurrence and development of neurodegenerative diseases is related to a variety of physiological and pathological changes. Neuroinflammation is one of the major factors that induces and aggravates neurodegenerative diseases. The most important manifestation of neuroinflammation is the activation of microglia. Therefore, inhibiting the abnormal activation of microglia is an important way to alleviate the occurrence of neuroinflammatory diseases. In this research, the inhibitory effect of tabersonine (Tab) on neuroinflammation was evaluated by establishing the BV2 neuroinflammation model induced by lipopolysaccharide (LPS). It was found that Tab significantly inhibited the production and expression of nitric oxide (NO), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and reactive oxygen species (ROS) in BV-2 cells stimulated by LPS. In addition, Tab can also inhibit the activation of nuclear factor-κB (NF-κB) induced by LPS, thus regulating inflammatory mediators such as inducible nitric oxide synthase (iNOS). These results indicated that Tab regulated the release of inflammatory mediators such as NO, IL-1ß, TNF-α, and IL-6 by inhibiting NF-κB signaling pathway, and exerting its anti-neuroinflammatory effect. This is the first report regarding the inhibition on LPS-induced neuroinflammation in BV2 microglia cells of Tab, which indicated the drug development potential of Tab for the treatment of neurodegenerative diseases.


Asunto(s)
Lipopolisacáridos , FN-kappa B , Humanos , FN-kappa B/metabolismo , Lipopolisacáridos/farmacología , Microglía , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Antiinflamatorios/uso terapéutico , Óxido Nítrico Sintasa de Tipo II/metabolismo , Transducción de Señal , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Óxido Nítrico/metabolismo
10.
Molecules ; 27(20)2022 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-36296442

RESUMEN

Pancreatic cancer is the seventh leading cause of cancer-related death worldwide and is known as "the king of cancers". Currently, gemcitabine (GEM) as the clinical drug of choice for chemotherapy of advanced pancreatic cancer has poor drug sensitivity and ineffective chemotherapy. Nardoguaianone L (G-6) is a novel guaiane-type sesquiterpenoid isolated from Nardostachys jatamansi DC., and it exhibits anti-tumor activity. Based on the newly discovered G-6 with anti-pancreatic cancer activity in our laboratory, this paper aimed to evaluate the potential value of the combination of G-6 and GEM in SW1990 cells, including cell viability, cell apoptosis, colony assay and tandem mass tags (TMT) marker-based proteomic technology. These results showed that G-6 combined with GEM significantly inhibited cell viability, and the effect was more obvious than that with single drug. In addition, the use of TMT marker-based proteomic technology demonstrated that the AGE-RAGE signaling pathway was activated after medication-combination. Furthermore, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) assays were used to validate the proteomic results. Finally, apoptosis was detected by flow cytometry. In conclusion, G-6 combined with GEM induced an increase in ROS level and a decrease in MMP in SW1990 cells through the AGE-RAGE signaling pathway, ultimately leading to apoptosis. G-6 improved the effect of GEM chemotherapy and may be used as a potential combination therapy for pancreatic cancer.


Asunto(s)
Nardostachys , Neoplasias Pancreáticas , Especies Reactivas de Oxígeno/farmacología , Proteómica , Línea Celular Tumoral , Neoplasias Pancreáticas/patología , Transducción de Señal , Apoptosis , Proliferación Celular , Gemcitabina , Neoplasias Pancreáticas
11.
Phytochemistry ; 200: 113228, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35561851

RESUMEN

Five previously unreported terpenoids, together with fifteen known analogs, were isolated from a methanol extract of the roots and rhizomes of Nardostachys jatamansi. Their structures, including absolute configurations, were elucidated by spectroscopic data and electronic circular dichroism (ECD) spectra analyses, as well as single-crystal X-ray diffraction for crystalline compounds. Structurally, (4R,5S,6S,7R)-1(10)-aristolane-8,9-diacid is a novel 8,9-dicarboxylic acid derivative of aristolane-type sesquiterpenoid. (4R,6S,7R,10S)-10-Hydroxyguaia-1(5)-6,7-epoxy-2-one is an undescribed analogue of nardoguaianone K, with a rare 6,7-epoxide group. (4R,5R,6R,8R)-1(10)-Isonardosinone-8-ol-9-one-7,11-lactone is an isonardosinane-type sesquiterpene bearing a γ-lactone ring. Dinardokanshone F is a rare example of a sesquiterpene dimer from N. jatamansi connected by an oxo bridge. The isolates were evaluated for their cytotoxic activity against four human pancreatic cancer cell lines (CFPAC-1, PANC-1, CAPAN-2 and SW1990). Compound epoxynardosinone exhibited significant cytotoxicity against CAPAN-2 cell lines with IC50 value of 2.60 ± 1.85 µM. 1-Hydroxylaristolone displayed comparable cytotoxicity on CFPAC-1 cell lines (IC50 1.12 ± 1.19 µM), compared to Taxol (IC50 0.32 ± 0.13 µM). 1-Hydroxylaristolone, 1(10)-aristolane-9ß-ol, 1(10)-aristolen-2-one, alpinenone, valtrate isovaleroyloxyhydrine and nardostachin displayed stronger cytotoxicity against PANC-1 cell lines with IC50 values ranging from 0.01 ± 0.01 to 6.50 ± 1.10 µM. 1(10)-Aristolane-9ß-ol, 10-hydroxyguaia-1(5)-6,7-epoxy-2-one, nardoguaianone K, nardonoxide, epoxynardosinone, 1(10)-isonardosinone-8-ol-9-one-7,11-lactone, valtrate isovaleroyloxyhydrine and nardostachin showed remarkable cytotoxicity against SW1990 cell lines with IC50 values ranging from 0.07 ± 0.05 to 4.82 ± 6.96 µM. Furthermore, the primary mechanistic study of nardostachin demonstrated that it induced cell apoptosis via the mitochondria-dependent pathway, and induced SW1900 cell arrest at G2/M phase.


Asunto(s)
Antineoplásicos , Nardostachys , Neoplasias Pancreáticas , Sesquiterpenos , Línea Celular , Humanos , Lactonas , Estructura Molecular , Nardostachys/química , Neoplasias Pancreáticas/tratamiento farmacológico , Sesquiterpenos/química , Sesquiterpenos/farmacología , Terpenos/farmacología
12.
J Asian Nat Prod Res ; 24(9): 820-826, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34662216

RESUMEN

Two new coumarins (1-2) have been isolated from a methanol extract of Zanthoxylum schinifolium branches. The structures of compounds 1 and 2 have been elucidated as 6-isopentenyl -7-benzoyl-coumarin and 3-isopentenyl-7-benzoyl-coumarin based on extensive spectroscopic analysis, including IR, NMR, and MS. The inhibitory activity of compounds 1 and 2 against HeLa and HepG2 cell lines has been described.


Asunto(s)
Zanthoxylum , Cumarinas/química , Cumarinas/farmacología , Metanol , Estructura Molecular , Extractos Vegetales/química , Zanthoxylum/química
13.
J Clin Lab Anal ; 35(12): e23773, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34767671

RESUMEN

BACKGROUND: miR-145 is closely related to vascular smooth muscle cells (VSMC) phenotype transformation; however, the regulatory mechanisms through which miR-145 regulates the VSMC phenotype transformation under mechanical stretching are unclear. In this study, we evaluated the roles of miR-145 in VSMCs subjected to mechanical stretching in aortic dissection (AD). METHODS: The expression of miR-145 in the aortic vessel wall of model animals and patients with AD was analyzed by quantitative polymerase chain reaction. miR-145-related protein-protein interaction networks and Wikipathways were used to analyze VSMC phenotypic transformation pathways regulated by miR-145. We used gain- and loss-of-function studies to evaluate the effects of miR-145 on VSMC differentiation under mechanical stretch induction and assessed whether Krüppel-like factor 4 (KLF4) was regulated by miR-145 in the aorta under mechanical stretch conditions. RESULTS: miR-145 was abundantly expressed in the walls of the normal human aorta, but was significantly downregulated in animal models and the walls of patients with dissection. We found that contractile phenotype-related proteins were downregulated in VSMCs subjected to mechanical stretching, whereas the expression of secreted phenotype-related proteins increased. miR-145 overexpression also downregulated contractile phenotype-related proteins in VSMCs and suppressed upregulation of phenotype-related proteins. Finally, under mechanical stretching, KLF4 expression was significantly increased in VSMCs, and overexpression of miR-145 blocked this effect. CONCLUSION: Our results confirmed that mechanical stretch-induced phenotypic transformation of VSMCs to promote AD via upregulation of KLF4; this mechanism was regulated by miR-145, which directly modulated KLF4 expression and VSMC differentiation.


Asunto(s)
Disección Aórtica/genética , MicroARNs/genética , Músculo Liso Vascular/patología , Disección Aórtica/patología , Animales , Fenómenos Biomecánicos , Diferenciación Celular/genética , Células Cultivadas , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Humanos , Factor 4 Similar a Kruppel/genética , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Músculo Liso Vascular/fisiología , Fenotipo , Mapas de Interacción de Proteínas/genética , Ratas Sprague-Dawley
14.
Chem Biodivers ; 18(12): e2100436, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34664781

RESUMEN

Three undescribed hydroxycinnamic acid amide dimers 1-3 were isolated and identified from an extract of Goji berry. Their molecular structures were elucidated based on NMR, MS, and IR spectra analysis. Compounds 1-3 were hydroxycinnamic acid amide dimers, which possess a cyclic butane moiety formed by head-to-head connection. These compounds at 25 µM showed the disaggregation potency on the copper-mediated Aß1-42 aggregation ranging from 27.3±3.2 to 31.0±2.9 %. This study provides new information on the antiaging traditional usage of goji berry.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Amidas/farmacología , Ácidos Cumáricos/farmacología , Lycium/química , Fármacos Neuroprotectores/farmacología , Extractos Vegetales/farmacología , Enfermedad de Alzheimer/metabolismo , Amidas/química , Amidas/aislamiento & purificación , Péptidos beta-Amiloides/antagonistas & inhibidores , Péptidos beta-Amiloides/metabolismo , Ácidos Cumáricos/química , Ácidos Cumáricos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Humanos , Conformación Molecular , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Fragmentos de Péptidos/antagonistas & inhibidores , Fragmentos de Péptidos/metabolismo , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Agregado de Proteínas/efectos de los fármacos
15.
PLoS One ; 16(5): e0250948, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33970943

RESUMEN

Ship collision accidents are the primary threat to traffic safety in the sea. Collision accidents can cause casualties and environmental pollution. The collision risk is a major indicator for navigators and surveillance operators to judge the collision danger between meeting ships. The number of collision accidents per unit time in a certain water area can be considered to describe the regional collision risk However, historical ship collision accidents have contingencies, small sample sizes and weak regularities; hence, ship collision conflicts can be used as a substitute for ship collision accidents in characterizing the maritime traffic safety situation and have become an important part of methods that quantitatively study the traffic safety problem and its countermeasures. In this work, an EMD-QPSO-LSSVM approach, which is a hybrid of empirical mode decomposition (EMD) and quantum-behaved particle swarm optimization (QPSO) optimized least squares support vector machine (LSSVM) model, is proposed to forecast ship collision conflicts. First, original ship collision conflict time series are decomposed into a collection of intrinsic mode functions (IMFs) and a residue with EMD. Second, both the IMF components and residue are applied to establish the corresponding LSSVM models, where the key parameters of the LSSVM are optimized by QPSO algorithm. Then, each subseries is predicted with the corresponding LSSVM. Finally, the prediction values of the original ship collision conflict datasets are calculated by the sum of the forecasting values of each subseries. The prediction results of the proposed method is compared with GM, Lasso regression method, EMD-ENN, and the predicted results indicate that the proposed method is efficient and can be used for the ship collision conflict prediction.


Asunto(s)
Prevención de Accidentes/métodos , Accidentes/estadística & datos numéricos , Medición de Riesgo/métodos , Navíos/normas , Máquina de Vectores de Soporte , Algoritmos , Simulación por Computador , Humanos , Análisis de los Mínimos Cuadrados , Modelos Teóricos , Estadística como Asunto , Taiwán
16.
Comput Intell Neurosci ; 2021: 6663446, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33727911

RESUMEN

In order to design an optimized route for ships in line with economic benefits; avoid bad weather; reduce unnecessary detours; shorten the navigation time; and achieve the purpose of safety, fuel saving, and punctual arrival, this paper takes the navigation mark as the node of the tree, takes the connection of the adjacent navigation marks as the tree path, and divides the distance of the adjacent buoys by the ship's speed as the path cost. The speed calculation collects the current hydrometeorological data such as wind and wave data, uses Aertssen's deceleration formula to adjust the speed, and improves Dijkstra to find the shortest path. In the experiment, two routes from Dongdu to Xiamen Gang Kou are compared under bad weather conditions. Route 1 is with 5.877 m/s average wind speed, 0.860 m/s wave speed, and total distance 34717 m. Route 2 is with 8.503 m/s average wind speed, 1.429 m/s wave speed, and total distance 30223 m. The calculated ship speed travelling in route 1 is 12.243 km, and its travelling time is 1.53 h. The calculated ship speed travelling in route 2 is 10.523 km, and its travelling time is 1.55 h. Although the total distance of route 1 is longer, it takes less time for ships to travel in route 1. The experimental results verify the effectiveness of the navigation algorithm based on the shortest path tree of uncertain weather maps.


Asunto(s)
Navíos , Árboles , Viaje , Incertidumbre , Viento
17.
J Org Chem ; 86(16): 11006-11010, 2021 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-33326231

RESUMEN

Narjatamolide (1), an unusual homoguaiane sesquiterpene lactone, was isolated from the roots and rhizomes of Nardostachys jatamansi DC. It represents the new carbon skeleton of a homoguaiane sesquiterpenoid possessing an additional acetate unit spiro-fused with C-4 and C-15 to form a cyclopropane ring. The structure of 1 was elucidated by extensive spectroscopic analyses, and the absolute configuration was confirmed by the electronic circular dichroism (ECD) calculations and X-ray single-crystal diffraction analysis. Compound 1 showed antiproliferative effects against BEL-7402 cell lines with an IC50 value of 5.67 ± 1.43 µM, and the mechanism study showed that 1 induces cell cycle of BEL-7402 cell lines arrest at G2/M phase.


Asunto(s)
Nardostachys , Sesquiterpenos , Lactonas/farmacología , Estructura Molecular , Rizoma , Sesquiterpenos/farmacología
18.
J Org Chem ; 85(16): 10806-10812, 2020 08 21.
Artículo en Inglés | MEDLINE | ID: mdl-32702985

RESUMEN

Bungsteroid A (1), possessing an unreported carbon skeleton, was isolated from the pericarps of Zanthoxylum bungeanum Maxim. It represents the first carbon skeleton of a C34 steroid analogue featuring a unique 6/6/6/6/5-fused pentacyclic skeleton, which has been determined by spectroscopic methods, quantum-chemical 13C NMR, ECD calculations, and calculations of optical rotations. Bungsteroid A showed the antiproliferative effects against HepG2, MCF-7, and HeLa cell lines with the IC50 values of 56.3 ± 1.1, 64.2 ± 0.9, and 74.2 ± 1.3 µM, respectively.


Asunto(s)
Zanthoxylum , Células HeLa , Humanos , Esteroides/farmacología
19.
Phytochemistry ; 172: 112257, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31986448

RESUMEN

In this study, fourteen ingenane-type and nine jatrophane-type diterpenoids were isolated from Euphorbia kansui, including seven undescribed compounds. Kansuingenol A-C have the 6,7-vicinal diol moiety, and Kansuijatrophanol A and B possess the 11,12-vicinal diol moiety, both of which are rarely reported. 3,4-(Methylenedioxy) cinnamyl moiety was found for the first time in jatrophane-type diterpenoids, as shown in Kansuijatrophanol C and D. The absolute configurations of seven undescribed compounds have been analyzed and assigned by the modified Mosher's method, Mo2(OAc)4-induced circular dichroism (ICD) method, and CD exciton chirality method. All compounds were screened for their antiproliferative effects against HepG2, MCF-7 and DU145 cell lines. Regarding the HepG2 cells, Kansuijatrophanol C exhibited the most promising inhibition with the IC50 value of 9.47 ± 0.31 µM. Regarding the MCF-7 and DU145 cells, Kansuijatrophanol D exhibited the most promising inhibition with the IC50 values of 6.29 ± 0.18 and 4.19 ± 0.32 µM, respectively.


Asunto(s)
Diterpenos , Euphorbia , Línea Celular , Estructura Molecular
20.
Nat Prod Bioprospect ; 9(6): 419-423, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31728851

RESUMEN

Diterpenoid alkaloids have neroprotective activity. Herein, three napelline-type diterpenoid alkaloids 1-3, two aconitine-type diterpenoid alkaloids 4-5, and one isoquinline-type alkaloid 6, as well as one lignan glycoside 7, have been isolated from the roots of Aconitum pendulum Busch. Compounds 1 and 7 were new compounds, and their chemical structures were determined on the basis of nuclear magnetic resonance (NMR) spectra and mass spectrometry analysis. A ThT assay revealed that compound 2 showed significant disaggregation potency on the Aß1-42 aggregates.

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