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1.
Animals (Basel) ; 14(9)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38731340

ABSTRACT

Heterosis refers to the phenomenon where hybrids exhibit superior performance compared to the parental phenotypes and has been widely utilized in crossbreeding programs for animals and crops, yet the molecular mechanisms underlying this phenomenon remain enigmatic. A better understanding of the gene expression patterns in post-hatch chickens is very important for exploring the genetic basis underlying economically important traits in the crossbreeding of chickens. In this study, breast muscle and liver tissues (n = 36) from full-sib F1 birds and their parental pure lines were selected to identify gene expression patterns and differentially expressed genes (DEGs) at 28 days of age by strand-specific RNA sequencing (ssRNA-seq). This study indicates that additivity is the predominant gene expression pattern in the F1 chicken post-hatch breast muscle (80.6% genes with additivity) and liver (94.2% genes with additivity). In breast muscle, Gene Ontology (GO) enrichment analysis revealed that a total of 11 biological process (BP) terms closely associated with growth and development were annotated in the identified DEG sets and non-additive gene sets, including STAT5A, TGFB2, FGF1, IGF2, DMA, FGF16, FGF12, STAC3, GSK3A, and GRB2. Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation presented that a total of six growth- and development-related pathways were identified, involving key genes such as SLC27A4, GLUL, TGFB2, COX17, and GSK3A, including the PPAR signaling pathway, TGF-beta signaling pathway, and mTOR signaling pathway. Our results may provide a theoretical basis for crossbreeding in domestic animals.

2.
Neuropsychopharmacology ; 49(8): 1318-1329, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38438592

ABSTRACT

Clinical studies have shown that the mediodorsal thalamus (MD) may play an important role in the development of depression. However, the molecular and circuit mechanisms by which the mediodorsal thalamus (MD) participates in the pathological processes of depression remain unclear. Here, we show that in male chronic social defeat stress (CSDS) mice, the calcium signaling activity of glutamatergic neurons in MD is reduced. By combining conventional neurotracer and transneuronal virus tracing techniques, we identify a synaptic circuit connecting MD and medial prefrontal cortex (mPFC) in the mouse. Brain slice electrophysiology and fiber optic recordings reveal that the reduced activity of MD glutamatergic neurons leads to an excitatory-inhibitory imbalance of pyramidal neurons in mPFC. Furthermore, activation of MD glutamatergic neurons restores the electrophysiological properties abnormal in mPFC. Optogenetic activation of the MD-mPFC circuit ameliorates anxiety and depression-like behaviors in CSDS mice. Taken together, these data support the critical role of MD-mPFC circuit on CSDS-induced depression-like behavior and provide a potential mechanistic explanation for depression.


Subject(s)
Depression , Mice, Inbred C57BL , Neural Pathways , Optogenetics , Prefrontal Cortex , Social Defeat , Stress, Psychological , Animals , Prefrontal Cortex/metabolism , Stress, Psychological/physiopathology , Male , Depression/physiopathology , Neural Pathways/physiopathology , Mice , Mediodorsal Thalamic Nucleus , Neurons/physiology , Neurons/metabolism , Pyramidal Cells/physiology
3.
Mater Today Bio ; 22: 100755, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37593217

ABSTRACT

Postoperative peritoneal adhesion (PPA) is frequent and extremely dangerous complication after surgery. Different tactics have been developed to reduce it. However, creating a postoperative adhesion method that is multifunctional, biodegradable, biocompatible, low-toxic but highly effective, and therapeutically applicable is still a challenge. Herein, we have prepared a degradable spray glycyrrhetinic acid hydrogel (GAG) based on natural glycyrrhetinic acid (GA) by straightforward heating and cooling without the use of any additional chemical cross-linking agents to prevent postoperative adhesion. The resultant hydrogel was demonstrated to possess various superior anti-inflammatory activity, and multiple functions, such as excellent degradability and biocompatibility. Specifically, spraying characteristic and excellent antibacterial activities essentially eliminated secondary infections during the administration of drugs in surgical wounds. In the rat models, the carrier-free spray GAG could not only slow-release GA to inhibit inflammatory response, but also serve as physical anti-adhesion barrier to reduce collagen deposition and fibrosis. The sprayed GAG would shed a new light on the prevention of postoperative adhesion and broaden the application of the hydrogels based on natural products in biomedical fields.

5.
Genes (Basel) ; 14(7)2023 07 17.
Article in English | MEDLINE | ID: mdl-37510361

ABSTRACT

Reducing abdominal fat (AF) accumulation and increasing the level of intramuscular fat (IMF) simultaneously is a major breeding goal in the poultry industry. To explore the different molecular mechanisms underlying AF and IMF, gene expression profiles in the breast muscle (BM) and AF from three chicken breeds were analyzed. A total of 4737 shared DEGs were identified between BM and AF, of which 2602 DEGs were upregulated and 2135 DEGs were downregulated in the BM groups compared with the AF groups. DEGs involved in glycerophospholipid metabolism and glycerolipid metabolism were potential regulators, resulting in the difference in lipid metabolite accumulation between IMF and AF. The PPAR signaling pathway was the most important pathway involved in tissue-specific lipid deposition. Correlation analysis showed that most representative DEGs enriched in the PPAR signaling pathway, such as FABP5, PPARG, ACOX1, and GK2, were negatively correlated with PUFA-enriched glycerophospholipid molecules. Most DEGs related to glycerophospholipid metabolism, such as GPD2, GPD1, PEMT, CRLS1, and GBGT1, were positively correlated with glycerophospholipid molecules, especially DHA- and arachidonic acid (ARA)-containing glycerophospholipid molecules. This study elucidated the molecular mechanism underlying tissue-specific lipid deposition and poultry meat quality.


Subject(s)
Chickens , Gene Expression Profiling , Animals , Gene Expression Profiling/methods , Chickens/genetics , Chickens/metabolism , PPAR gamma/genetics , Abdominal Fat/metabolism , Lipids
6.
Heliyon ; 9(5): e15866, 2023 May.
Article in English | MEDLINE | ID: mdl-37305497

ABSTRACT

In this paper, we use the method of principal-form analysis, based on 836 consumer survey data obtained from mobile Internet, and analyze the trust of current residents' tea consumption behavior on information content, presentation form, subject and other elements of information tools and their influence on the pollution-free certified products with the help of descriptive statistical analysis, KMO test and common factor extraction method. It was found that, firstly, the higher the trust of tea consumers in information content, the higher the additional willingness to pay; secondly, the form trust also significantly affects tea consumers' willingness to pay for pollution-free certified tea, and the specific cognitive information presentation form can effectively enhance tea consumers' willingness to pay; thirdly, there are significant differences in the trust of subjects, and enhancing the trust of industrial subjects helps to improve the pollution-free certified industrial The effect of trust of external subjects is not significant; fourth, the higher the tea consumers' care about the attributes of experienced products, the higher the degree of knowledge about the three products and one standard, and the higher the consumers' education, the higher they are willing to pay higher prices for traceable tea.

7.
Biomed Pharmacother ; 165: 115041, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37356374

ABSTRACT

Nanoscience has set off a wave in biomedicine to improve the performance of drugs in recent years, but additional materials are usually required for supramolecular nanoconstruction, undoubtedly increasing the health risks. Herein, we discovered a novel diterpene supramolecular self-assembly system without additional chemicals, Nepebracteatalic Acid nanoparticles (NA NPs), mediated through hydrogen bond, hydrophobic and electrostatic interaction. NA NPs performed sustained release behavior, lower expression levels for IL-6 and TNF-α than clinical anti-inflammatory drug Indometacin. Furthermore, the effect of NA NPs on the related protein p65 expression levels of nuclear factor-κB (NFκB) signaling pathway is quantified to confirm the enhanced anti-inflammatory property based on the self-assembly strategy. Meanwhile, the prepared nanoparticles have good biocompatibility which ensures outstanding inflammation inhibition, collagen deposition, angiogenesis during wound healing. This work opens up new prospects that carrier-free nanoparticles from NPMs have great potential to exert clinical application value, meanwhile providing reference for developing green nanoscience.


Subject(s)
Diterpenes , Nanoparticles , NF-kappa B/metabolism , Wound Healing , Nanoparticles/chemistry , Anti-Inflammatory Agents/pharmacology , Diterpenes/pharmacology
8.
Int Wound J ; 20(9): 3884-3897, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37337711

ABSTRACT

Surgical Site Infection (SSI) is one of the common postoperative complications after gastric cancer surgery. Previous studies have explored the risk factors (such as age, diabetes, anaemia and ASA score) for SSI in patients with gastric cancer. However, there are large differences in the research results, and the correlation coefficients of different research results are quite different. We aim to investigate the risk factors of surgical site infection in patients with gastric cancer. We queried four English databases (PubMed, Embase, Web of Science and the Cochrane Library) and four Chinese databases (China National Knowledge Infrastructure, Chinese Biological Medicine Database, Wanfang Database and Chinese Scientific Journal Database (VIP Database)) to identify published literature related to risk factors for surgical site infection in patients with gastric cancer. Rev Man 5.4 and Stata 15.0 were used in this meta-analysis. A total of 15 articles (n = 6206) were included in this analysis. The following risk factors were found to be significantly associated with surgical site infection in gastric cancer: male (OR = 1.28, 95% CI [1.06, 1.55]), age >60 (OR = 2.75, 95% CI [1.65, 4.57]), smoking (OR = 1.99, 95% CI [1.46, 2.73]), diabetes (OR = 2.03, 95% CI [1.59, 2.61]), anaemia (OR = 4.72, 95% CI [1.66, 13.40]), preoperative obstruction (OR = 3.07, 95% CI [1.80, 5.23]), TNM ≥ III (OR = 2.05, 95% CI [1.56, 2.70]), hypoproteinemia (OR = 3.05, 95% CI [2.08, 4.49]), operation time ≥3 h (OR = 8.33, 95% CI [3.81, 18.20]), laparotomy (OR = 2.18, 95% CI [1.61, 2.94]) and blood transfusion (OR = 1.44, 95% CI [1.01, 2.06]). This meta-analysis showed that male, age >60, smoking, diabetes, anaemia, preoperative obstruction, TNM ≥ III, hypoproteinemia, operation time ≥3 h, open surgery and blood transfusion were the risk factors for SSI in patients with gastric cancer.


Subject(s)
Anemia , Diabetes Mellitus , Hypoproteinemia , Stomach Neoplasms , Humans , Male , Surgical Wound Infection/epidemiology , Surgical Wound Infection/etiology , Stomach Neoplasms/surgery , Stomach Neoplasms/complications , Risk Factors , Hypoproteinemia/complications
9.
Mol Neurobiol ; 60(4): 2277-2294, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36645630

ABSTRACT

Hepatic encephalopathy (HE) is a nervous system disease caused by severe liver diseases and different degrees of learning and memory dysfunction. Long non-coding RNA (lncRNA) is highly expressed in the brain and plays important roles in central nervous system diseases like Alzheimer's disease. In the present work, we found that the expression of lnc240 in the hippocampus of HE mice was significantly downregulated, but its pathogenesis in HE has not been clarified. This study aimed to explore the effects of lnc240 on the cognitive function of HE. The expression of lnc240, miR-1264-5p, and MEF2C was analyzed with RNA-seq and further determined by qRT-PCR in HE mouse. Double luciferase reporter gene testing confirmed the relationship between lnc240, MEF2C, and miR-1264-5p. The functional role of lnc240 and MEF2C in vitro and in vivo was evaluated by qRT-PCR, western blot analysis, immunofluorescence staining, Golgi staining, electrophysiology, and Morris water maze. The expression of lnc240 was decreased in HE mice. The overexpression of lnc240 could significantly downregulate miR-1264-5p and upregulate MEF2C, also increasing the amplitude and frequency of mEPSC in primary cultured hippocampal neurons. The overexpression of miR-1264-5p reversed the effect of lnc240 on MEF2C. Moreover, in vivo experiments have shown that the overexpression of lnc240 could improve HE mice's spatial learning and memory functions. Golgi staining suggested that overexpression of lnc240 could increase the density and maturity of dendritic spines in hippocampal neurons of HE mice. Lnc240 can regulate the expression of MEF2C through miR-1264-5p and regulate the synaptic plasticity of hippocampal neurons, thereby saving the learning and memory dysfunction in HE mice, suggesting that lnc240 might be a potential therapeutic target for the treatment of HE.


Subject(s)
Alzheimer Disease , Hepatic Encephalopathy , MicroRNAs , RNA, Long Noncoding , Mice , Animals , MicroRNAs/genetics , Maze Learning , RNA, Long Noncoding/genetics , MEF2 Transcription Factors
10.
Molecules ; 28(2)2023 Jan 04.
Article in English | MEDLINE | ID: mdl-36677566

ABSTRACT

Microglia are neuroglia in the brain with an innate immune function and participate in the progress of neurodegenerative diseases. Osthole (OST) is a coumarin derivative extracted from Cnidium monnieri and bears a microglia-antagonizing ability. However, the underlying mechanism of the antagonism is not clear. The lipopolysaccharides-induced microglial BV2 cell line and amyloid-overexpressing fruit fly were used as models to study OST treatment. We found that OST treatment is sufficient to evoke NRF2 cascade under an LPS-induced inflammatory environment, and silencing NRF2 is sufficient to abolish the process. Moreover, we found that OST is sufficient to antagonize microglial activation in both LPS-induced BV2 cells and Aß-overexpressing fruit flies, and silencing NRF2 abolishes OST's antagonism. Furthermore, OST treatment rescued survival, climbing, and the learning ability of Aß-overexpressing fruit flies and relieved oxidative stress. In conclusion, we proved that OST antagonizes microglial activation induced by either LPS or Aß and that NRF2 is necessary for OST's antagonism.


Subject(s)
Coumarins , Microglia , Coumarins/pharmacology , Lipopolysaccharides , Microglia/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Animals , Mice , Cell Line , Drosophila
11.
Brain Res ; 1804: 148264, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36702182

ABSTRACT

Cognitive impairment is one of the most common symptoms of hepatic encephalopathy (HE). However, there is a lack of easily implementable rehabilitation strategies. As an easy-to-implement strategy, numerous studies suggest that enriched environment (EE) can be beneficial for cognitive function. However, the effects of EE on learning and memory, as well as dendritic spines plasticity in HE is still unclear. Accordingly, in the present study, we evaluated the effects of EE on the behavior and dendritic spine morphology in an animal model of HE. Our results showed that HE mice have no movement disorder and anxiety, but they exhibit spatial learning and memory dysfunction. Further analysis revealed that the complexity of the dendrites and the maturity of the dendritic spines are reduced in the hippocampus of HE mice. After 4 weeks of housekeeping in EE, dendritic complexity, and dendritic spine maturity, as well as the spatial learning and memory function of HE mice were restored. In conclusion, exposure to EE can positively influence dendritic spines plasticity in the hippocampus and thereby elicit its beneficial effects on cognitive functions in HE.


Subject(s)
Dendritic Spines , Hepatic Encephalopathy , Mice , Animals , Hippocampus , Spatial Learning , Memory Disorders , Dendrites
12.
Anim Biotechnol ; 34(7): 3074-3084, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36244007

ABSTRACT

In diploid organisms, interactions between alleles determine phenotypic variation. In previous experiments, only MYH1F was found to show both ASE (spatiotemporal allele-specific expression) and TRD (allelic transmission ratio distortion) characteristics in the pectoral muscle by comparing the genome-wide allele lists of hybrid populations (F1) of meat- and egg- type chickens. In addition, MYH1F is a member of the MYH gene family, which plays an important role in skeletal muscle and non-muscle cells of animals, but the specific expression and function of this gene in chickens are still unknown. Therefore, qRT-PCR was used to detect the expression of MYH1F in different tissues of chicken. Proliferation and differentiation of chicken skeletal muscle satellite cells (SMSCs) have been detected by transfection of MYH1F-specific small interfering RNA (siRNA). The results showed that the expression of MYH1F in chicken skeletal muscle was higher than that in other tissues. Combined with CCK-8 assay, EdU assay, immunofluorescence, and Western blot Assay, it was found that MYH1F knockdown could significantly suppress the proliferation of chicken SMSCs and depress the differentiation and fusion of the cells. These results suggest that MYH1F plays a critical role in myogenesis in poultry, which is of great significance for exploring the regulatory mechanisms of muscle development and improving animal productivity.


Subject(s)
Chickens , Satellite Cells, Skeletal Muscle , Animals , Chickens/genetics , Cell Differentiation/genetics , Muscle Fibers, Skeletal , Muscle, Skeletal , RNA, Small Interfering , Cell Proliferation/genetics , Muscle Development/physiology
13.
Food Funct ; 13(24): 12487-12509, 2022 Dec 13.
Article in English | MEDLINE | ID: mdl-36413139

ABSTRACT

Glycyrrhetinic acid (GA), a famous natural product, has been attracting more attention recently because of its remarkable biological activity, natural sweetness, and good biocompatibility. In the past few years, a considerable amount of literature has grown up around the theme of GA-based chemical modification to broaden its functional applications. Promising structures including gels, micelles, nanoparticles, liposomes, and so forth have been constantly reported. On the one hand, the assembly mechanisms of various materials based on GA derivatives have been elucidated via modern analytical techniques. On the other hand, their potential application prospects in edible additives, intelligent drug delivery, and other fields have been investigated fully due to availability, biocompatibility, and controllable degradability. Inspired by these findings, a systematic summary and classification of the materials formed by GA derivatives seems necessary and meaningful. This review sums up the new functional applications of GA derivatives for the first time and provides better prospects for their application and development.


Subject(s)
Glycyrrhetinic Acid , Nanoparticles , Glycyrrhetinic Acid/chemistry , Micelles , Drug Delivery Systems/methods , Liposomes
14.
Molecules ; 27(20)2022 Oct 13.
Article in English | MEDLINE | ID: mdl-36296463

ABSTRACT

Indole diterpenes are a large class of secondary metabolites produced by fungi, possessing a cyclic diterpenoid backbone and an indole moiety. Novel structures and important biological activity have made indole diterpenes one of the focuses of synthetic chemists. Although the discovery, identification, structural diversity, biological activity and especially structure-activity relationship of indole diterpenes have been reported in some papers in recent years, they are absent of a systematic and comprehensive analysis, and there is no elucidation of enzymes related to this kind of natural product. Therefore, it is necessary to summarize the relevant reports to provide new perspectives for the following research. In this review, for the first time, the function of related synthases and the structure-activity relationship of indole diterpenes are expounded, and the recent research advances of them are emphasized.


Subject(s)
Biological Products , Diterpenes , Diterpenes/chemistry , Fungi/metabolism , Indoles/chemistry , Biological Products/pharmacology , Biological Products/metabolism
15.
Transl Psychiatry ; 12(1): 380, 2022 09 10.
Article in English | MEDLINE | ID: mdl-36088395

ABSTRACT

Clinical studies have shown that social defeat is an important cause of mood-related disorders, accompanied by learning and memory impairment in humans. The mechanism of mood-related disorders has been widely studied. However, the specific neural network involved in learning and memory impairment caused by social defeat remains unclear. In this study, behavioral test results showed that the mice induced both learning and memory impairments and mood-related disorders after exposure to chronic social defeat stress (CSDS). c-Fos immunofluorescence and fiber photometry recording confirmed that CaMKIIα expressing neurons of the piriform cortex (PC) were selectively activated by exposure to CSDS. Next, chemogenetics and optogenetics were performed to activate PC CaMKIIα expressing neurons, which showed learning and memory impairment but not mood-related disorders. Furthermore, chemogenetic inhibition of PC CaMKIIα expressing neurons significantly alleviated learning and memory impairment induced by exposure to CSDS but did not relieve mood-related disorders. Therefore, our data suggest that the overactivation of PC CaMKIIα expressing neurons mediates CSDS-induced learning and memory impairment, but not mood-related disorders, and provides a potential therapeutic target for learning and memory impairment induced by social defeat.


Subject(s)
Piriform Cortex , Social Defeat , Animals , Anxiety , Humans , Memory Disorders , Mice , Stress, Psychological
16.
Int J Mol Sci ; 23(17)2022 Sep 05.
Article in English | MEDLINE | ID: mdl-36077576

ABSTRACT

BACKGROUND: Imidacloprid (IMD) is a widely used neonicotinoid-targeting insect nicotine acetylcholine receptors (nAChRs). However, off-target effects raise environmental concerns, including the IMD's impairment of the memory of honeybees and rodents. Although the down-regulation of inotropic glutamate receptor (iGluR) was proposed as the cause, whether IMD directly manipulates the activation or inhibition of iGluR is unknown. Using electrophysiological recording on fruit fly neuromuscular junction (NMJ), we found that IMD of 0.125 and 12.5 mg/L did not activate glutamate receptors nor inhibit the glutamate-triggered depolarization of the glutamatergic synapse. However, chronic IMD treatment attenuated short-term facilitation (STF) of NMJ by more than 20%. Moreover, by behavioral assays, we found that IMD desensitized the fruit flies' response to mechanosensitive, nociceptive, and photogenic stimuli. Finally, the treatment of the antioxidant osthole rescued the chronic IMD-induced phenotypes. We clarified that IMD is neither agonist nor antagonist of glutamate receptors, but chronic treatment with environmental-relevant concentrations impairs glutamatergic plasticity of the NMJ of fruit flies and interferes with the sensory response by mediating oxidative stress.


Subject(s)
Drosophila Proteins , Drosophila melanogaster , Animals , Coumarins , Drosophila/metabolism , Drosophila Proteins/metabolism , Drosophila melanogaster/genetics , Neonicotinoids/pharmacology , Neuronal Plasticity/physiology , Nitro Compounds , Nociception , Oxidative Stress , Receptors, Glutamate/metabolism
17.
Gene ; 842: 146801, 2022 Oct 30.
Article in English | MEDLINE | ID: mdl-35961440

ABSTRACT

In China, the production mode of hybrid broilers with meat-type chicken as male parent and egg-type chicken as female parent is common, but few studies pay attention to the economic characteristics of hybrid broilers. In this experiment, we constructed a full-sib F1 population (n = 57) from male Recursive White broiler and female Lohmann Pink layer. Total 6, 6 and 7 hybrid broilers at days 1, 28 and 56 were selected randomly to collect breast muscle and liver tissues, respectively. After performing strand-specific RNA-Seq on these samples, we obtained 252.12 Gb sequencing data. Principal component analysis presented that the effects of different factors on gene expression were as below: tissue difference > age difference > sex difference. The ten genes with the highest expression in breast muscle were GAPDH, ACTA1, ATP2B3, COII, ATP6, COX3, COX1, MYL1, TNNI2 and ENSGALG00000042024. Through the analysis of differentially expressed transcripts (DETs) between different ages, we found that the number of DETs decreased progressively with the prolongation of ages in breast muscle. The same results were also observed in liver. GO enrichment analysis of DETs demonstrated that total 11 BP terms closely related to growth and development of breast muscle were annotated, such as cardiac muscle contract, muscle contract, cell division and so on. KEGG annotation presented that total 5 pathways related to growth and development were determined in breast muscle, including Cell cycle, Insulin signaling pathway, FoxO signaling pathway, Focal adhesion and Adrenergic signaling in cardiomyocytes. Our results may provide theoretical foundation for hybrid broiler production.


Subject(s)
Chickens , Animals , Chickens/genetics , Female , Gene Expression Profiling , Liver , Male , Pectoralis Muscles , Transcriptome
18.
Molecules ; 27(14)2022 Jul 19.
Article in English | MEDLINE | ID: mdl-35889467

ABSTRACT

From the dried vines of Aspidopterys obcordata Hemsl, five new polyoxypregnane glycosides, named obcordatas J-N (1-5), were obtained. Their structures were fully elucidated and characterized by HRESIMS and extensive spectroscopic data. In addition, all of the new compounds were screened for their antinephrolithiasis activity in vitro. The results showed that compounds 1-3 have prominent protective effects on calcium oxalate crystal-induced human kidney 2 (HK-2) cells, with EC50 values ranging from 6.72 to 14.00 µM, which is consistent with the application value of A. obcordata in folk medicine for kidney stones.


Subject(s)
Drugs, Chinese Herbal , Malpighiaceae , Saponins , Drugs, Chinese Herbal/chemistry , Glycosides/chemistry , Glycosides/pharmacology , Humans , Malpighiaceae/chemistry , Molecular Structure , Saponins/chemistry
19.
Bioorg Chem ; 127: 106013, 2022 10.
Article in English | MEDLINE | ID: mdl-35841667

ABSTRACT

In the present study, six new cucurbitane type compounds, including three triterpenoids hemsleyacins P-R (6-7, 13) and three cucurbitane-type triterpenoid glycosides hemsleyaosides L-N (15-17), along with seventeen known cucurbitacin analogues were separated from the root tuber of Hemsleya penxianensis and elucidated based on NMR and HRESIMS. Then, 23 analogues of three types, namely, polyhydroxy-type (I) (1-7), monohydroxy-type (II) (8-13), and glycosides-type (III) (14-23), were assessed for their antitumor activity and structure-activity relationship analysis (SAR). We determined temozolomide (TMZ)-resistant GBM cell was the most sensitive to the tested compounds, and found hemsleyaoside N (HDN) displayed the best antineoplastic potency. Furthermore, we confirmed the anti-glioma activity of HDN in patient-derived recurrent GBM strains, GBM organoid (GBO) and orthotopic nude mouse models. Investigations exploring the mechanism made clear that HDN induced synchronous activation of UPR and MAPK signaling, which triggered deadly ER stress and apoptosis. Taken together, the potent antitumor activity of HDN warrants further comprehensive evaluation as a novel anti-glioma agent.


Subject(s)
Cucurbitaceae , Glioma , Triterpenes , Animals , Apoptosis , Cell Line, Tumor , Cucurbitaceae/chemistry , Drug Resistance, Neoplasm , Glioma/drug therapy , Glioma/pathology , Glycosides/chemistry , Glycosides/pharmacology , Mice , Triterpenes/chemistry , Triterpenes/pharmacology
20.
Fitoterapia ; 161: 105251, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35803523

ABSTRACT

Three novel geranylhydroquinone derived meroterpenoids, named clavilactones J and K (1-2) and clavipol C (3), were isolated from the basidiomycete Clitocybe clavipes. Their structures were unambiguously identified by extensive spectroscopic data analysis, and the electronic circular dichroism (ECD) calculation, Gauge-Including Atomic Orbitals (GIAO) NMR calculations and Mo2(OAc)4-induced electronic circular dichroism experiments were used to establish their absolute configurations. Compound 1, with two epoxy groups located at the 10-membered carbocycle, is uncommon in the reported meroterpenoids from C. clavipes. All the obtained compounds (1-3) were tested for their cytotoxic activity against human tumor cell line HGC-27 by using the MTT assay. All the compounds exhibited moderate cytotoxic activities against HGC-27 cell with IC50 values ranging from 33.5 to 56.6 µM.


Subject(s)
Agaricales , Antineoplastic Agents , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Humans , Molecular Structure , Terpenes
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