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1.
Exp Ther Med ; 27(5): 202, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38590576

RESUMO

Dixon surgery for rectal cancer can lead to severe intestinal narrowing and blockage that is difficult to treat with open surgery or colonoscopy. The aim of the present study was to develop a minimally invasive approach for treating rectal anastomotic atresia based on three cases that were managed with transurethral prostate resection instrumentation. Preoperative imaging determined the distance from the anastomotic closure to the anal margin, the length of the anastomotic closure and the degree of proximal intestinal dilation for all cases. During the procedure, the anastomotic site was visualized, and a circular electrode was used to excavate and open the blockage. Membrane-like closures were directly incised to achieve satisfactory results, with an anastomotic diameter >20 mm. Those cases with tubular atresia required an initial incision using the prostate resectoscope to relieve the obstruction, followed by radial incisions until achieving an anastomotic diameter >20 mm. At 3-6 months post-dilation, two of the patients with anastomotic atresia >20 mm had satisfactory bowel movements, whereas the remaining patient experienced tumor recurrence at the anastomotic site and discontinued treatment. This case series demonstrates the potential of transurethral prostate resection instrumentation as a safe and effective minimally invasive approach for rectal anastomotic atresia. Given that prostate resection instrumentation is readily available in hospitals in China, this approach is widely accessible to most patients. Furthermore, the technique leverages existing surgical technology and practices, requiring only a shift in the surgical site.

2.
Int J Mol Sci ; 25(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38473980

RESUMO

Liver fibrosis poses a significant global health risk due to its association with hepatocellular carcinoma (HCC) and the lack of effective treatments. Thus, the need to discover additional novel therapeutic targets to attenuate liver diseases is urgent. Leucine-rich repeat containing 1 (LRRC1) reportedly promotes HCC development. Previously, we found that LRRC1 was significantly upregulated in rat fibrotic liver according to the transcriptome sequencing data. Herein, in the current work, we aimed to explore the role of LRRC1 in liver fibrosis and the underlying mechanisms involved. LRRC1 expression was positively correlated with liver fibrosis severity and significantly elevated in both human and murine fibrotic liver tissues. LRRC1 knockdown or overexpression inhibited or enhanced the proliferation, migration, and expression of fibrogenic genes in the human hepatic stellate cell line LX-2. More importantly, LRRC1 inhibition in vivo significantly alleviated CCl4-induced liver fibrosis by reducing collagen accumulation and hepatic stellate cells' (HSCs) activation in mice. Mechanistically, LRRC1 promoted HSC activation and liver fibrogenesis by preventing the ubiquitin-mediated degradation of phosphorylated mothers against decapentaplegic homolog (Smad) 2/3 (p-Smad2/3), thereby activating the TGF-ß1/Smad pathway. Collectively, these results clarify a novel role for LRRC1 as a regulator of liver fibrosis and indicate that LRRC1 is a promising target for antifibrotic therapies.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratos , Humanos , Camundongos , Animais , Células Estreladas do Fígado/metabolismo , Leucina/metabolismo , Regulação para Cima , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Cirrose Hepática/metabolismo , Fígado/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Proteínas Smad/metabolismo
3.
Org Biomol Chem ; 22(11): 2271-2278, 2024 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-38391281

RESUMO

Two previously unreported lignans (1-2) and four undescribed [11]-chaetoglobosins (3-6) were obtained from the culture extract of an endophytic fungus Pseudeurotium bakeri P1-1-1. Their structures with absolute configurations were determined by spectroscopic data analysis, single-crystal X-ray diffraction, electronic circular dichroism (ECD) calculations, the modified Mosher's method, and Mo2(OAc)4-induced electronic circular dichroism (ICD) experiments. Compounds 5 and 6 showed moderate cytotoxic effects against seven human cancer cell lines. Compounds 2-4 exhibited immunosuppressive activities on concanavalin A-induced T cell proliferation with IC50 values of 3.7, 3.4, and 14.5 µM, and on lipopolysaccharide-induced B cell proliferation with IC50 values of 4.1, 3.9, and 14.2 µM, respectively. Further investigation revealed that 2 and 3 induced apoptosis in activated T cells in a dose-dependent manner.


Assuntos
Ascomicetos , Lignanas , Humanos , Lignanas/química , Linhagem Celular , Alcaloides Indólicos , Imunossupressores , Estrutura Molecular
4.
Biochim Biophys Acta Mol Basis Dis ; 1870(4): 167054, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38360074

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and is a serious threat to human health; thus, early diagnosis and adequate treatment are essential. However, there are still great challenges in identifying the tipping point and detecting early warning signals of early HCC. In this study, we aimed to identify the tipping point (critical state) of and key molecules involved in hepatocarcinogenesis based on time series transcriptome expression data of HCC patients. The phase from veHCC (very early HCC) to eHCC (early HCC) was identified as the critical state in HCC progression, with 143 genes identified as key candidate molecules by combining the DDRTree (dimensionality reduction via graph structure learning) and DNB (dynamic network biomarker) methods. Then, we ranked the candidate genes to verify their mRNA levels using the diethylnitrosamine (DEN)-induced HCC mouse model and identified five early warning signals, namely, CCT3, DSTYK, EIF3E, IARS2 and TXNRD1; these signals can be regarded as the potential early warning signals for the critical state of HCC. We identified CCT3 as an independent prognostic factor for HCC, and functions of CCT3 involving in the "MYCtargets_V1" and "E2F-Targets" are closely related to the progression of HCC. The predictive method combining the DDRTree and DNB methods can not only identify the key critical state before cancer but also determine candidate molecules of critical state, thus providing new insight into the early diagnosis and preemptive treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/patologia , Carcinogênese/genética , Carcinogênese/patologia , Biomarcadores , Transcriptoma , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Chaperonina com TCP-1/genética , Chaperonina com TCP-1/metabolismo
5.
J Antibiot (Tokyo) ; 77(1): 21-29, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37957338

RESUMO

New ambuic acid derivatives, pestallic acids R-V (1-5), together with ambuic acid (6), were isolated from the endophytic fungus Pestalotiopsis trachicarpicola SC-J551 derived from the fern Blechnum orientale L., of which compound 2, being racemic, was separated to two optically pure enantiomers (+)-2 and (-)-2. The structures including absolute configurations of these new compounds were elucidated by extensive spectroscopic analysis and theoretical simulations of their ECD spectra and 13C NMR chemical shifts. Compounds 1 and 3 exhibited cytotoxicity against human carcinoma A549, HeLa, HepG2, and MCF-7 cells (IC50: 3.6-12.5 µM) and compound 3 was also active against Staphylococcus aureus and MRSA (MIC = 20 µg ml-1). Compound (±)-2 showed inhibitory activity against LPS-induced NO release (IC50 = 21.1 µM) and t-BHP-induced ROS production (IC50 = 8.5 µM) in RAW264.7 macrophages.


Assuntos
Fungos , Pestalotiopsis , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular
6.
Saudi Pharm J ; 32(1): 101889, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38090737

RESUMO

The present study utilized molecular docking and density functional theory (DFT) approaches, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties to investigate the binding interactions, reactivity, stability, and drug-likeness of curcumin (1), tetrahydrocurcumin (2), and tetrahydrocurcumin derivatives (3-6) as potential anti-cancer agents. MGL (Molecular Graphic Laboratory) and Discovery Studio Visualizer (DSV) software employed for docking studies. Pharmacokinetic and pharmacodynamic (ADME-Tox) analyses were conducted using SwissADME and pKCSM web servers. Total Electron Density (TED) measurements identified molecular adsorption sites, considering various factors, including quantum chemical characteristics, to assess compound effectiveness using DFT method implanted in the Gaussian software. The binding energy (Eb) from docking simulations was used to evaluate inhibitory potential. ADMET analysis suggested favorable oral bioavailability and pharmacokinetics for all studied substances, excluding compound 4. DFT and docking investigations highlighted compounds 1, 2, and 6 as optimal scaffolds for drug design based on in silico screening tests.

7.
Chin Med ; 18(1): 157, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38037150

RESUMO

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a refractory disease with high mortality, which is characterized by a pathophysiological process of inflammation-related dysfunction of energy metabolism. Jieduan-Niwan formula (JDNWF) is a eutherapeutic Chinese medicine formula for ACLF. However, the intrinsic mechanism of its anti-ACLF effect still need to be studied systematically. PURPOSE: This study aimed to investigate the mechanism of JDNWF against ACLF based on altered substance metabolic profile in ACLF the expression levels of related molecules. MATERIALS AND METHODS: The chemical characteristics of JDNWF were characterized using ultra performance liquid chromatography (UPLC) coupled with triple quadrupole mass spectrometry. Wistar rats subjected to a long-term CCL4 stimulation followed by a combination of an acute attack with LPS/D-GalN were used to establish the ACLF model. Liver metabolites were analyzed by LC-MS/MS and multivariate analysis. Liver function, coagulation function, histopathology, mitochondrial metabolic enzyme activity and mitochondrial damage markers were evaluated. The protein expression of mitochondrial quality control (MQC) was investigated by western blot. RESULTS: Liver function, coagulation function, inflammation, oxidative stress and mitochondrial enzyme activity were significantly improved by JDNWF. 108 metabolites are considered as biomarkers of JDNWF in treating ACLF, which were closely related to TCA cycle. It was further suggested that JDNWF alleviated mitochondrial damage and MQC may be potential mechanism of JDNWF improving mitochondrial function. CONCLUSIONS: Metabolomics revealed that TCA cycle was impaired in ACLF rats, and JDNWF had a regulatory effect on it. The potential mechanism may be improving the mitochondrial function through MQC pathway, thus restoring energy metabolism.

8.
J Nat Prod ; 86(11): 2571-2579, 2023 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-37947788

RESUMO

Eleven new phenyltetracenoid polyketides, streptovertimycins U (1) and V (2), 14-bromo-streptovertidione (3), streptovertimycins W-Y (4-6), and streptovertimycins Z1-Z5 (7-11), together with the known congeners fasamycins R (12) and S (13) and accramycins A (14) and B (15), were isolated from the NaBr-supplemented rice-grown cultures of Streptomyces morookaense SC1169. Their structures were elucidated by extensive spectroscopic analysis, single-crystal X-ray diffraction analysis, and theoretical computations of ECD spectra. Compounds 1 and 2 are methylene-bridged dimers of accramycin A, and compounds 3 and 7-11 are brominated fasamycin congeners. Compounds 5 and 8-14 exhibited activity against the drug-resistant bacteria MRSA and VRE (MIC = 0.6-5.0 µg/mL), and the dimer 1 displayed activity against MRSA (MIC = 2.5 µg/mL). Compounds 6-15 showed cytotoxicity against the human carcinoma A549, HeLa, HepG2, and MCF-7 cells in the IC50 range between 1.7 and 9.2 µM.


Assuntos
Streptomyces , Humanos , Streptomyces/química , Células HeLa , Análise Espectral , Células MCF-7 , Antibacterianos/química , Estrutura Molecular
9.
Food Res Int ; 172: 112562, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37689837

RESUMO

Daylily (Hemerocallis citrina Baroni, HC) is an edible plant and is traditionally considered with potential to improve sleep. Herein, based on the Drosophila activity monitoring, metabolome, targeted screening and transcriptome, the material basis and mechanism of HC on sleep-improvement was investigated. The results showed that the aqueous extracts of HC (HAE) as well as the ethanol extracts (HEE) all prolonged the total sleep time of insomnia fruit flies, especially HEE-60 and HEE-95 exhibited more significant effects. In addition, 539 of 728 found metabolites were screened as potential sleep-improved metabolites, and quercetin, linoleic acid, phenethyl caffeate, L-methionine and γ-aminobutyric acid were considered as core active metabolites. Meanwhile, 368 differentially expressed genes (DEGs) were revealed by transcriptomics analysis, and the neuroactive ligand-receptor interaction was deduced as the main pathway by KEGG pathway enrichment. Furthermore, nine DEGs located in this pathway, namely betaTry, deltaTry, gammaTry, epsilonTry, etaTry, iotaTry, lambdaTry, kappaTry and CG30031 were proven being up-regulated. All these results contribute to the development of HC-related functional foods.


Assuntos
Hemerocallis , Transcriptoma , Animais , Drosophila , Perfilação da Expressão Gênica , Sono
10.
Int J Biol Macromol ; 252: 126246, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37567520

RESUMO

Root bark (Lycii cortex) of Lycium contains high contents of characteristic bioactive compounds, including kukoamine A (KuA) and kukoamine B (KuB). RIPENING INHIBITOR (RIN) is well known as a master regulator of Solanaceaous fruit ripening. However, the role of RIN in the biosynthetic pathway of KuA in Lycium remains unclear. In this study, integrated transcriptomic, metabolomic analyses and hairy root system are used to characterize the role of RIN in KuA biosynthesis in Lycium. The ultra performance liquid chromatography electrospray ionization tandem mass spectrometry analysis revealed that KuA was significantly induced in LrRIN1 RNAi lines and not detected in overexpression lines. A total of 20,913 differentially expressed genes (DEGs) and 60 differentially accumulated metabolites (DAMs) were detected in LrRIN1 transgenic hairy roots, which were used for weighted gene co-expression network analysis. Our result reveals a high association between KuA and structural genes in the phenolamide pathway, which shows a negative correlation with LrRIN1. In addition, overexpression of the polyamine pathway gene thermospermine synthase LcTSPMS, a potential target gene of Lycium RIN, increased the contents of both KuA and KuB in L. chinense hairy root, indicating that TSPMS is responsible for KuA biosynthesis and is also the common upstream biosynthetic gene for both KuA and KuB. Our results lay a solid foundation for uncovering the biosynthetic pathway of KuA, which will facilitate the molecular breeding and genetic improvement of Lycium species.


Assuntos
Lycium , Lycium/química , Espermina/farmacologia , Perfilação da Expressão Gênica , Frutas , Regulação da Expressão Gênica de Plantas
11.
Int J Antimicrob Agents ; 62(3): 106876, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37276892

RESUMO

Usnic acid, a representative dibenzofuran metabolite, is known to have antimicrobial properties. However, despite considerable interest as an antimicrobial agent, the mechanism by which usnic acid and its derivatives exert their action is not fully characterized. This article describes the synthesis of peziculone, a 5:1 equilibrium mixture of two inseparable usnic acid derivatives: peziculone A and peziculone B. The antibacterial activity of peziculone against several Gram-positive bacterial pathogens was found to be significantly better compared with usnic acid. Clustered regularly interspaced short palindromic repeats interference sequencing analysis and membrane fluorescent staining were used to demonstrate that peziculone destabilizes the cell walls of Gram-positive bacteria. Additionally, peziculone 2.5 and 3.5 µg/mL impaired cell surface appendages and biofilm formation by Staphylococcus aureus. Taken together, these data demonstrate that peziculone, a derivative compound of usnic acid, has significant antimicrobial activity against Gram-positive bacteria by targeting the cell walls; this provides a platform for development of novel antibacterial drugs.


Assuntos
Anti-Infecciosos , Bactérias Gram-Positivas , Antibacterianos/farmacologia , Parede Celular , Testes de Sensibilidade Microbiana
12.
Food Funct ; 14(10): 4595-4606, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37158204

RESUMO

This study aimed to investigate the impact of chitosan-grafted-caffeic acid (CS-g-CA) and ultrasound (US) on myofibrillar proteins (MPs) in pompano (Trachinotus ovatus) during 24 days of ice storage. Fresh fish slices were treated with US (20 kHz, 600 W), CS-g-CA (G), and US combined with CS-g-CA (USG) for 10 min, respectively. Samples treated with sterile water served as study controls (CK). All samples were then stored in ice at 4 °C. The oxidation and degradation of MPs were evaluated at 4-day intervals. The results showed that US slightly accelerated the fragmentation of myofibrils, as confirmed by the increased myofibril fragmentation index (MFI). However, on day 24, the surface hydrophobicity (SH) of USG samples was 4.09 µg BPB bound/mg protein lower than that of G samples, and the total sulfhydryl content of USG samples was 0.50 µmol g-1 higher than that of G samples, suggesting that US could reinforce the antioxidant capacity of CS-g-CA. Regarding degradation of MPs, USG treatment maintained the secondary and tertiary structure of MPs by reducing the transition from ordered to disordered structures and by reducing the exposure of tryptophan residues. Sodium dodecyl sulphate- polyacrylamide gel electrophoresis (SDS-PAGE) showed that the inhibitory effect of USG on protein degradation may be related to the binding of CS-g-CA to MPs. The results of scanning electron microscopy (SEM) further clarified the fact that the USG treatment can protect the myofibril microstructure by maintaining the compact arrangement of muscle fibers. Additionally, USG treatment could improve the sensory properties of pompano. Overall, the synergistic effects of US and CS-g-CA can effectively delay the protein oxidation and degradation. The results provided in this study are valuable for the quality maintenance of marine fish.


Assuntos
Quitosana , Gelo , Animais , Oxirredução , Antioxidantes , Peixes
13.
Phytochemistry ; 210: 113679, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37059288

RESUMO

Five previously undescribed specialized metabolites, including three 9,11-seco-pimarane diterpenoids, nodulisporenones A-C, and two androstane steroids, nodulisporisterones A and B, together with previously described ergosterol derivatives, dankasterone A and demethylincisterol A3, were isolated from solid cultures of the endophytic fungus Nodulisporium sp. SC-J597. Their structures including absolute configurations were elucidated by extensive spectroscopic analysis and theoretical calculations of electronic circular dichroism spectra. Among them, nodulisporenones A and B are the first examples of seco-pimarane diterpenoids that is cyclized to form an unprecedented diterpenoid lactone scaffold and nodulisporisterones A and B represent the first normal C19 androstane steroids of fungal origin. Nodulisporisterone B exhibited potent inhibitory effect on the production of NO in LPS-stimulated RAW264.7 macrophages (IC50 = 2.95 µM). This compound, together with the two known ergosterol derivatives, also displayed cytotoxicity against A549, HeLa, HepG2 and MCF-7 cancer cell lines with IC50 values of 5.2-16.9 µM.


Assuntos
Abietanos , Diterpenos , Humanos , Abietanos/química , Estrutura Molecular , Esteroides , Diterpenos/química , Androstanos , Fungos , Ergosterol
14.
Food Chem ; 420: 136093, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37062084

RESUMO

Two novel chitosan oligosaccharide (COS)-hydroxypyridone (HPO) conjugates were prepared by reacting chitosan oligosaccharide with 2-chloromethyl-5-hydroxypyridone (HPO), which was synthesized by a series of reactions starting from kojic acid. The degree of substitution of COS-HPO2 reached 1.2, with a yield of 74.9%. The structure of the two conjugates (COS-HPO1 and COS-HPO2) was identified by NMR and FT-IR analysis. The two conjugates showed significantly higher free radical (DPPH•, ABTS+• and •OH) scavenging activity and reducing power than those of COS and HPO (p < 0.05). Both COS-HPO1 and COS-HPO2 possessed significantly stronger tyrosinase inhibitory activity than those of COS, with IC50 values of 0.67 and 0.28 mg/mL for monophenolase, 0.73 and 0.30 mg/mL for diphenolase, respectively. In addition, the conjugates were found to be non-toxic to RAW264.7 macrophages and MRC-5 human lung cells. This work proposes a facile method to enhance the oxidative and tyrosinase inhibitory properties of COS.


Assuntos
Quitosana , Monofenol Mono-Oxigenase , Monofenol Mono-Oxigenase/química , Monofenol Mono-Oxigenase/metabolismo , Oligossacarídeos/química , Oligossacarídeos/farmacocinética , Antioxidantes/química , Antioxidantes/farmacologia , Humanos , Espectroscopia de Infravermelho com Transformada de Fourier
15.
Int J Biol Macromol ; 235: 123930, 2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-36889616

RESUMO

This study aimed to reveal the constipation-relieving role of chitosan (COS) with different molecular weights (1 kDa, 3 kDa and 244 kDa). Compared with COS3K (3 kDa) and COS240K (244 kDa), COS1K (1 kDa) more significantly accelerated gastrointestinal transit and defecation frequency. These differential effects were reflected in the regulation of specific gut microbiota (Desulfovibrio, Bacteroides, Parabacteroides and Anaerovorax) and short-chain fatty acids (propionic acid, butyric acid and valeric acid). RNA-sequencing found that the differential expressed genes (DEGs) caused by different molecular weights of COS were mainly enriched in intestinal immune-related pathways, especially cell adhesion molecules. Furthermore, network pharmacology revealed two candidate genes (Clu and Igf2), which can be regarded as the key molecules for the differential anti-constipation effects of COS with different molecular weights. These results were further verified by qPCR. In conclusion, our results provide a novel research strategy to help understand the differences in the anti-constipation effects of chitosan with different molecular weights.


Assuntos
Quitosana , Animais , Camundongos , Ácido Butírico , Quitosana/farmacologia , Constipação Intestinal/metabolismo , Peso Molecular , Farmacologia em Rede , Propionatos/química
17.
Int J Mol Sci ; 24(5)2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36902274

RESUMO

Daylily (Hemerocallis citrina Baroni) is an edible plant widely distributed worldwide, especially in Asia. It has traditionally been considered a potential anti-constipation vegetable. This study aimed to investigate the anti-constipation effects of daylily from the perspective of gastro-intestinal transit, defecation parameters, short-chain organic acids, gut microbiome, transcriptomes and network pharmacology. The results show that dried daylily (DHC) intake accelerated the defecation frequency of mice, while it did not significantly alter the levels of short-chain organic acids in the cecum. The 16S rRNA sequencing showed that DHC elevated the abundance of Akkermansia, Bifidobacterium and Flavonifractor, while it reduced the level of pathogens (such as Helicobacter and Vibrio). Furthermore, a transcriptomics analysis revealed 736 differentially expressed genes (DEGs) after DHC treatment, which are mainly enriched in the olfactory transduction pathway. The integration of transcriptomes and network pharmacology revealed seven overlapping targets (Alb, Drd2, Igf2, Pon1, Tshr, Mc2r and Nalcn). A qPCR analysis further showed that DHC reduced the expression of Alb, Pon1 and Cnr1 in the colon of constipated mice. Our findings provide a novel insight into the anti-constipation effects of DHC.


Assuntos
Constipação Intestinal , Hemerocallis , Laxantes , Animais , Camundongos , Constipação Intestinal/terapia , Microbioma Gastrointestinal , Hemerocallis/química , Farmacologia em Rede , RNA Ribossômico 16S , Laxantes/química , Laxantes/farmacologia , Laxantes/uso terapêutico , Ceco/efeitos dos fármacos
18.
Artigo em Inglês | MEDLINE | ID: mdl-36762500

RESUMO

Squamocin, an annonaceous acetogenin isolated from plants in the Annonaceae family, has antitumour activity. In this study, we report that Sq-2, a biotinylated squamocin monomer, has a favorable antitumour effect on MDA-MB-231 and SKBR3 breast cancer cells in vitro. MTT assays show that Sq-2 has a better antitumour effect on MDA-MB-231 cells than Sq-5 and Sq-6. Furthermore, RNA-Seq and KEGG enrichment analyses reveal that Sq-2 activates the MAPK signaling pathway, and results of western blot analysis demonstrate that Sq-2 activates the JNK and p38 pathways in MDA-MB-231 and SKBR3 cells. Flow cytometry and western blot analysis reveal that Sq-2 induces cell apoptosis by increasing the expressions of cleaved Caspase-3 and cleaved PARP as well as the ratio of Bax/Bcl-2. Inhibition of the Caspase family by Z-VAD-FMK attenuates the viability of MDA-MB-231 cells, indicating that Sq-2 induces apoptosis in a Caspase-dependent manner. Additionally, pretreatment with the p38 inhibitor SB203580 or JNK inhibitor SP600125 partially reverses the increase in the apoptosis rate and decrease in cell viability prompted by Sq-2. Furthermore, Sq-2 treatment decreases the expression level of CyclinD1 and increases the expression levels of p21, p27, CyclinA1, and CDK2, causing S-phase arrest in MDA-MB-231 and SKBR3 cells. Further study indicates that Sq-2 stimulates autophagy in MDA-MB-231 and SKBR3 cells, and inhibition of autophagy by bafilomycin A1 increases cell viability and promotes cell survival. Sq-2, a novel biotin-squamocin compound, shows a significant inhibitory effect on the propagation of SKBR3 and MDA-MB-231 breast cancer cells. Furthermore, Sq-2 treatment not only induces S-phase arrest and activates the JNK and p38 pathways to trigger apoptosis but also causes autophagy to promote apoptosis in MDA-MB-231 and SKBR3 cells.

.

19.
Phytochemistry ; 207: 113582, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36596436

RESUMO

Alnus cremastogyne Burkill (Betulaceae), an actinorhizal plant, can enter a mutualistic symbiosis with Frankia species that leads to the formation of nitrogen fixing root nodules. Some primary metabolites (carbohydrates, dicarboxylic acids, amino acids, citrulline and amides) involved in carbon and nitrogen metabolism in actinorhizal nodules have been identified, while specialized metabolites in A. cremastogyne root nodules are yet to be characterized. In this study, we isolated and identified three undescribed 3-pentanol glycosides, i.e., 3-pentyl α-l-arabinofuranosyl-(1''→6')-ß-d-glucopyranoside, 3-pentyl α-l-rhamnopyranosyl-(1''→6')-ß-d-glucopyranoside, and 3-pentyl 6'-(3-hydroxy3-methylglutaryl)-ß-d-glucopyranoside, as well as seventeen known compounds from A. cremastogyne root nodules. 3-Pentanol glycosides are abundantly distributed in root nodules, while they are distributed in stems, roots, leaves and fruits at low/zero levels. A. cremastogyne plants treated by root nodule suspension emit 3-pentanol. This study enriches the knowledge about specialized metabolites in the actinorhizal host, and provides preliminarily information on the signal exchange in the actinorhizal symbiosis between A. cremastogyne and Frankia.


Assuntos
Alnus , Frankia , Pentanóis/metabolismo , Glicosídeos/metabolismo , Raízes de Plantas , Frankia/metabolismo , Simbiose , Plantas , Nitrogênio/metabolismo , Fixação de Nitrogênio , Nódulos Radiculares de Plantas
20.
Nat Prod Res ; 37(3): 462-467, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34544305

RESUMO

Two new α-pyrones, micropyrones A (1) and B (2), along with four known γ-pyrones, nocapyrone D (3), nocapyrone A (4), marinactinone A (5), and nocapyrone H (6), were isolated from the culture extract of actinomycete Microbacterium sp. GJ312, which was isolated from Glycyrrhiza uralensis. The structures of these compounds were identified by analysis of spectral data. They are the first α- and γ-pyrones reported from the genus Microbacterium. The antibacterial activity of all compounds against Staphylococcus aureus and methicillin resistant S. aureus was evaluated. However, none of them showed significant activity. This study represents the first phytochemical example of a Glycyrrhiza-derived actinomycete.


Assuntos
Actinobacteria , Glycyrrhiza uralensis , Glycyrrhiza , Staphylococcus aureus Resistente à Meticilina , Glycyrrhiza uralensis/química , Pironas , Microbacterium
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