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1.
Bioorg Chem ; 151: 107619, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39024806

RESUMO

Two rare 8-hydroxysteroid glycosides (6-7), and their downstream metabolites (1-5) with an unprecedented 6/6/5/5/5-pentacyclic scaffold, together with seven known analogues (8-14) were isolated from the twigs and leaves of Strophanthus divaricatus. Their structures were fully assigned by analysis of the spectroscopic and ECD data, NMR calculations, X-ray crystallographic study, and chemical methods. In addition, the inhibitory effects of 1-14 on liver and lung cancer cell lines were evaluated, and preliminary structure-activity relationship was discussed. Data-independent acquisition (DIA)-based quantitative proteomic analysis and biological verification of H1299 cells suggested that this family of compounds may play an anticancer role by suppressing both DNA damage response (DDR) and mTOR/S6K signaling pathways.

2.
Nutrients ; 16(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38892715

RESUMO

NASH (non-alcoholic steatohepatitis) is a severe liver disease characterized by hepatic chronic inflammation that can be associated with the gut microbiota. In this study, we explored the therapeutic effect of Gynostemma pentaphyllum extract (GPE), a Chinese herbal extract, on methionine- and choline-deficient (MCD) diet-induced NASH mice. Based on the peak area, the top ten compounds in GPE were hydroxylinolenic acid, rutin, hydroxylinoleic acid, vanillic acid, methyl vanillate, quercetin, pheophorbide A, protocatechuic acid, aurantiamide acetate, and iso-rhamnetin. We found that four weeks of GPE treatment alleviated hepatic confluent zone inflammation, hepatocyte lipid accumulation, and lipid peroxidation in the mouse model. According to the 16S rRNA gene V3-V4 region sequencing of the colonic contents, the gut microbiota structure of the mice was significantly changed after GPE supplementation. Especially, GPE enriched the abundance of potentially beneficial bacteria such as Akkerrmansia and decreased the abundance of opportunistic pathogens such as Klebsiella. Moreover, RNA sequencing revealed that the GPE group showed an anti-inflammatory liver characterized by the repression of the NF-kappa B signaling pathway compared with the MCD group. Ingenuity Pathway Analysis (IPA) also showed that GPE downregulated the pathogen-induced cytokine storm pathway, which was associated with inflammation. A high dose of GPE (HGPE) significantly downregulated the expression levels of the tumor necrosis factor-α (TNF-α), myeloid differentiation factor 88 (Myd88), cluster of differentiation 14 (CD14), and Toll-like receptor 4 (TLR4) genes, as verified by real-time quantitative PCR (RT-qPCR). Our results suggested that the therapeutic potential of GPE for NASH mice may be related to improvements in the intestinal microenvironment and a reduction in liver inflammation.


Assuntos
Microbioma Gastrointestinal , Gynostemma , Hepatopatia Gordurosa não Alcoólica , Extratos Vegetais , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Camundongos , Gynostemma/química , Extratos Vegetais/farmacologia , Masculino , Inflamação/tratamento farmacológico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Transdução de Sinais/efeitos dos fármacos , Anti-Inflamatórios/farmacologia
3.
Zhongguo Gu Shang ; 37(6): 5655-70, 2024 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-38910378

RESUMO

OBJECTIVE: To explore high density lipoprotein (HDL)/low density lipoprotein (LDL) and total typeⅠcollagen amino terminal extender peptide (t-PINP)/ C-terminal peptide of typeⅠcollagen ß special sequence(ß-CTX)and risk of osteoporosis vertebral fractures (OPVFs) in elderly women. METHODS: The clinical data of 446 female OPVFs patients aged above 60 years old from January 2019 to December 2020 were retrospectively analyzed. According to whether or not fracture, patients were divided into non-fracture group (186 patients) and fracture group(260 patients). Univariate analysis was performed to analysis age, body mass index(BMI), N-terminal mioldle molecular fragment of osteocalcin, N-MID OC), t-PINP, ß-CTX, 25-hydroxyvitamin D[25-(OH) VitD], blood sugar (Glu), total cholesterol(TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), Ca, P, Mg, urea (UREA), creatinine (Cr) and Cystatin C(CysC), and correlation between OPVFs and the above indexes and lipid, bone metabolism indexes between two groups;Logistic regression was performed to analyze risk factors and stratification relationship between vertebral fracture and HDL/LDL, t-PINP/ß-CTX. Logistic regression was used to analyze risk factors and stratification relationship between OPVFs and HDL/LDL, t-PINP/ß-CTX. RESULTS: There were no significant difference in age and BMI between non-fracture group and fracture group (P>0.05). Compared with non-fracture group, contents of HDL, t-PINP/ß-CTX and HDL/LDL in fracture group were decreased, and contents of ß-CTX were increased (P<0.05). OPVFs was positively correlated with ß-CTX (r=0.110, P<0.05), and negatively correlated with HDL, HDL/LDL and t-PINP/ß-CTX (r=-0.157, -0.175, -0.181, P<0.05). HDL and HDL/LDL were negatively correlated with ß-CTX (r=-0.22, -0.12, P<0.05) and t-PINP (r=-0.13, -0.10, P<0.05). 25-(OH) VitD was positively correlated with TC and HDL (r=0.11, 0.18, P<0.05). HDL/LDL was positively correlated with t-PINP/ß-CTX(r=0.11, P=0.02). t-PINP/ß-CTX[OR=0.998, 95%CI(0.997, 1.000), P<0.05], HDL/LDL[OR=0.228, 95%CI(0.104, 0.499), P<0.01] were risk factors for vertebral fracture. The lower levels between two tristratified indicators, the higher the vertebral fracture rate. The risk of fracture was 2.5 and 2 times higher in the lowest stratum than in the highest stratum, with an adjusted OR was[2.112, 95%CI(1.310, 3.404)] and [2.331, 95%CI(1.453, 3.739)], respectively. CONCLUSION: Serum low HDL/LDL and t-PINP /ß-CTX are independent risk factors for OPVF in elderly women, and have good predictive value for OPVF risk.


Assuntos
Lipoproteínas LDL , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Humanos , Feminino , Idoso , Fraturas por Osteoporose/sangue , Fraturas da Coluna Vertebral/sangue , Lipoproteínas LDL/sangue , Pessoa de Meia-Idade , Estudos Retrospectivos , Lipoproteínas HDL/sangue , Pró-Colágeno/sangue , Fragmentos de Peptídeos/sangue , Colágeno Tipo I/sangue , Idoso de 80 Anos ou mais , Peptídeos/sangue , Osteocalcina/sangue
4.
Medicine (Baltimore) ; 103(25): e38651, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38905366

RESUMO

This study aimed to evaluate whether palliative surgery for metastatic lesion could provide a survival benefit in metastatic breast cancer (MBC) patients with solitary metastasis. De novo MBC patients with solitary distant lesions were enrolled utilizing the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was conducted to form matched pairs of the surgery group and the non-surgery group. The breast cancer-specific survival (BCSS) and overall survival (OS) outcomes between the 2 groups were compared in the following 3 sample models: the entire cohort of MBC (7665 cases); subgroups of patients with different isolated metastatic organs; and subgroups of patients with different molecular subtypes for each isolated metastatic organ. Compared with the Non-surgery group, the surgery group showed better BCSS and OS before PSM (HR = 0.88, 95% CI = 0.79-0.99, P = .04 and HR = 0.85, 95% CI = 0.76-0.95, P = .006, respectively). After PSM, palliative surgery still provided an OS benefit in patients with brain metastasis and lung metastasis (HR = 0.59, 95% CI = 0.37-0.95, P = .01 and HR = 0.64, 95% CI = 0.45-0.90, P = .02, respectively). Likewise, a better BCSS benefit was also found in the subset of patients with brain metastasis (HR = 0.61, 95% CI = 0.38-1.00, P = .01). Further stratification analysis indicated that patients with the luminal A subtype with brain metastasis have a better BCSS (HR = 0.36, 95% CI = 0.16-0.79, P = .04) and OS (HR = 0.37, 95% CI = 0.18-0.75, P = .03) after undergoing palliative surgery than nonsurgical treatment. Our study originality showed that palliative surgery for metastatic lesion could improve survival prognosis in patients with special single-organ metastasis and specific molecular subtypes. More clinical studies are needed to determine whether palliative surgery should be performed in MBC patients.


Assuntos
Neoplasias da Mama , Cuidados Paliativos , Pontuação de Propensão , Programa de SEER , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/mortalidade , Cuidados Paliativos/métodos , Pessoa de Meia-Idade , Idoso , Metástase Neoplásica , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/mortalidade , Adulto , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Estudos Retrospectivos
5.
Angew Chem Int Ed Engl ; 63(31): e202403066, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-38752880

RESUMO

Pure aromatic hydrocarbon materials (PHCs) represent a new generation of host materials for phosphorescent OLEDs (PhOLEDs), free of heteroatoms. They reduce the molecular complexity, can be easily synthesized and are an important direction towards robust devices. As heteroatoms can be involved in bonds dissociations in operating OLEDs through exciton induced degradation processes, developing novel PHCs appear particularly relevant for the future of this technology. In the present work, we report a series of extended PHCs constructed by the assembly of three spirobifluorene fragments. The resulting positional isomers present a high triplet energy level, a wide HOMO/LUMO difference and improved thermal and morphological properties compared to previously reported PHCs. These characteristics are beneficial for the next generation of host materials for PhOLEDs and provide relevant design guidelines. When used as a host in blue-emitting PhOLEDs, which are still the weakest link of the field, a very high EQE of 24 % and low threshold voltage of 3.56 V were obtained with a low-efficiency roll-off. This high performance strengthens the position of PHC strategy as an efficient alternative for OLED technology and opens the way to a more simple electronic.

6.
Nat Prod Rep ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38809164

RESUMO

Covering: 1976 to December 2023Chloranthaceae is comprised of four extant genera (Chloranthus, Sarcandra, Hedyosmum, and Ascarina), totaling about 80 species, many of which have been widely used as herbal medicines for diverse medical purposes. Chloranthaceae plants represent a rich source of structurally interesting and diverse secondary metabolites, with sesquiterpenoids and diterpenoids being the predominant structural types. Lindenane sesquiterpenoids and their oligomers, chemotaxonomical markers of the family Chloranthaceae, have shown a wide spectrum of bioactivities, attracting significant attention from organic chemists and pharmacologists. Recent achievements also demonstrated the research value of two unique structural types in this plant family, sesquiterpenoid-monoterpenoid heterodimers and meroterpenoids. This review systematically summarizes 682 structurally characterized terpenoids from 22 Chloranthaceae plants and their key biological activities as well as the chemical synthesis of selected terpenoids.

7.
Phytochemistry ; 223: 114138, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38762154

RESUMO

Croton laui (Euphorbiaceae) is a traditional medicinal plant used by the Li ethnic group in China to treat headaches, stomachaches, and diphtheria. To understand the pharmacological basis of its medicinal use, an extensive investigation of the ethanolic extract of the bark of C. laui was performed. After repeated chromatography, twenty-four undescribed labdane-type diterpenoids, lauinoids A-X (1-24), and five known analogs (25-29) were isolated. Their structures and absolute configurations were established using a combination of spectroscopic analyses, electronic circular dichroism, nuclear magnetic resonance calculations, and single-crystal X-ray diffraction. Among them, compounds 1-3 exhibited an 11(12 â†’ 13)-abeo-16-nor-labdane skeleton, which originated putatively from 9 through a plausible pathway that involves a semipinacol rearrangement process. Compounds 11 and 12 belong to the rare class of 14,15-dinor-labdane diterpenoids. Compounds 18 and 28 exhibited substantial inhibitory effects by suppressing lipopolysaccharide-induced NO production in RAW 264.7 macrophages, with IC50 values of 3.37 ± 0.23 and 5.82 ± 0.28 µM, respectively. This study has greatly expanded the chemical diversity of labdane diterpenoids from C. laui and will guide future research on this ethnomedicinal plant.


Assuntos
Anti-Inflamatórios , Croton , Diterpenos , Diterpenos/farmacologia , Diterpenos/química , Diterpenos/isolamento & purificação , Croton/química , Camundongos , Animais , Células RAW 264.7 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Estrutura Molecular , Relação Estrutura-Atividade , Óxido Nítrico/biossíntese , Óxido Nítrico/antagonistas & inibidores , Conformação Molecular , Relação Dose-Resposta a Droga
8.
J Nat Prod ; 87(5): 1441-1453, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38722764

RESUMO

Herein, we report an extensive phytochemical study on the whole plant of Drymaria cordata, which led to the isolation of ten new orbitides, named drymariamides A-J (1-10). Compounds 2, 3, and 5 incorporate rare residues of noncanonical amino acids of kynurenine (Kyn) or 3a-hydroxypyrroloindoline (HPI). Their structures with absolute configurations were elucidated by a combination of spectroscopic analysis, advanced Marfey's method, X-ray diffraction, and electronic circular dichroism analysis. Compounds 1-10 exhibited antiadipogenic effects in 3T3-L1 adipocytes, and the most potent compound 7 showed an EC50 value of 1.17 ± 0.19 µM.


Assuntos
Células 3T3-L1 , Aminoácidos , Peptídeos Cíclicos , Animais , Camundongos , Aminoácidos/química , Estrutura Molecular , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Adipogenia/efeitos dos fármacos , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo
9.
Front Cell Infect Microbiol ; 14: 1395716, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716195

RESUMO

Objective: The relationship between macrophages and the gut microbiota in patients with atherosclerosis remains poorly defined, and effective biological markers are lacking. This study aims to elucidate the interplay between gut microbial communities and macrophages, and to identify biomarkers associated with the destabilization of atherosclerotic plaques. The goal is to enhance our understanding of the underlying molecular pathways and to pave new avenues for diagnostic approaches and therapeutic strategies in the disease. Methods: This study employed Weighted Gene Co-expression Network Analysis (WGCNA) and differential expression analysis on atherosclerosis datasets to identify macrophage-associated genes and quantify the correlation between these genes and gut microbiota gene sets. The Random Forest algorithm was utilized to pinpoint PLEK, IRF8, BTK, CCR1, and CD68 as gut microbiota-related macrophage genes, and a nomogram was constructed. Based on the top five genes, a Non-negative Matrix Factorization (NMF) algorithm was applied to construct gut microbiota-related macrophage clusters and analyze their potential biological alterations. Subsequent single-cell analyses were conducted to observe the expression patterns of the top five genes and the interactions between immune cells. Finally, the expression profiles of key molecules were validated using clinical samples from atherosclerosis patients. Results: Utilizing the Random Forest algorithm, we ultimately identified PLEK, IRF8, CD68, CCR1, and BTK as gut microbiota-associated macrophage genes that are upregulated in atherosclerotic plaques. A nomogram based on the expression of these five genes was constructed for use as an auxiliary tool in clinical diagnosis. Single-cell analysis confirmed the specific expression of gut microbiota-associated macrophage genes in macrophages. Clinical samples substantiated the high expression of PLEK in unstable atherosclerotic plaques. Conclusion: Gut microbiota-associated macrophage genes (PLEK, IRF8, CD68, CCR1, and BTK) may be implicated in the pathogenesis of atherosclerotic plaques and could serve as diagnostic markers to aid patients with atherosclerosis.


Assuntos
Algoritmos , Aterosclerose , Biomarcadores , Microbioma Gastrointestinal , Aprendizado de Máquina , Macrófagos , Placa Aterosclerótica , Receptores CCR1 , Análise de Célula Única , Humanos , Macrófagos/metabolismo , Macrófagos/microbiologia , Placa Aterosclerótica/microbiologia , Biomarcadores/metabolismo , Análise de Célula Única/métodos , Receptores CCR1/metabolismo , Receptores CCR1/genética , Aterosclerose/microbiologia , Aterosclerose/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Tirosina Quinase da Agamaglobulinemia/genética , Tirosina Quinase da Agamaglobulinemia/metabolismo , Antígenos CD/metabolismo , Antígenos CD/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Molécula CD68 , Fatores Reguladores de Interferon
10.
Phytochemistry ; 224: 114163, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38815883

RESUMO

Stereochemical investigations on the twigs and leaves of Solanum erianthum afforded five pairs of lignanamide enantiomers and a previously undescribed phenolic amide (3). Particularly, two pairs of previously undescribed lignanamide racemates (1a/1b-2a/2b) represent the first case of natural products that feature an unreported 5/5-fused N/O-biheterocyclic core. Their structures, including the absolute configurations, were determined unambiguously by using spectroscopic analyses and electronic circular dichroism calculations. A speculative biogenetic pathway for 1-3 was proposed. Interestingly, these lignanamides exhibited enantioselective antiplasmodial activities against drug-sensitive Plasmodium falciparum 3D7 strain and chloroquine-resistant Plasmodium falciparum Dd2 strain, pointing out that chirality plays an important role in drug development.


Assuntos
Antimaláricos , Folhas de Planta , Plasmodium falciparum , Solanum , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/química , Antimaláricos/farmacologia , Antimaláricos/isolamento & purificação , Folhas de Planta/química , Solanum/química , Estereoisomerismo , Estrutura Molecular , Lignanas/química , Lignanas/farmacologia , Lignanas/isolamento & purificação , Amidas/química , Amidas/farmacologia , Amidas/isolamento & purificação , Relação Estrutura-Atividade , Testes de Sensibilidade Parasitária
11.
Chem Biodivers ; : e202401089, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740553

RESUMO

Croton sublyratus (Euphorbiaceae) is a traditional medicinal plant used by the Thai populace to treat helminthic infections and dermatologic conditions. In present study, eight new labdane-type diterpenoids, crotonoids A-H (1-8) and one known analogue (9) were isolated from the aerial parts of C. sublyratus. Compounds 6 and 7 belong to the rare class of 14,15-dinor-labdane diterpenoids. Compound 8 exhibited a rare 14,15,17-trinor-labdane skeleton. The structures of all these diterpenoids were elucidated by spectroscopic data analysis, electronic circular dichroism calculations, and single-crystal X-ray diffraction analysis. Compound 9 exhibited moderate anti-inflammatory activity via the inhibition of NO production in lipopolysaccharide-induced RAW 264.7 cells.

12.
Plant Physiol Biochem ; 210: 108615, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38631158

RESUMO

Magnesium is one of the essential nutrients for plant growth, and plays a pivotal role in plant development and metabolism. Soil magnesium deficiency is evident in citrus production, which ultimately leads to failure of normal plant growth and development, as well as decreased productivity. Citrus is mainly propagated by grafting, so it is necessary to fully understand the different regulatory mechanisms of rootstock and scion response to magnesium deficiency. Here, we characterized the differences in morphological alterations, physiological metabolism and differential gene expression between trifoliate orange rootstocks and lemon scions under normal and magnesium-deficient conditions, revealing the different responses of rootstocks and scions to magnesium deficiency. The transcriptomic data showed that differentially expressed genes were enriched in 14 and 4 metabolic pathways in leaves and roots, respectively, after magnesium deficiency treatment. And the magnesium transport-related genes MHX and MRS2 may respond to magnesium deficiency stress. In addition, magnesium deficiency may affect plant growth by affecting POD, SOD, and CAT enzyme activity, as well as altering the levels of hormones such as IAA, ABA, GA3, JA, and SA, and the expression of related responsive genes. In conclusion, our research suggests that the leaves of lemon grafted onto trifoliate orange were more significantly affected than the roots under magnesium-deficient conditions, further indicating that the metabolic imbalance of scion lemon leaves was more severe.


Assuntos
Citrus , Regulação da Expressão Gênica de Plantas , Magnésio , Plântula , Citrus/metabolismo , Citrus/genética , Plântula/metabolismo , Plântula/genética , Plântula/crescimento & desenvolvimento , Magnésio/metabolismo , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/genética , Deficiência de Magnésio/metabolismo , Folhas de Planta/metabolismo , Estresse Fisiológico , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética
13.
J Agric Food Chem ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602386

RESUMO

The genus Salix L. is traditionally used in folk medicine to alleviate pain caused by various kinds of inflammation. In the present study, 10 undescribed salicin derivatives along with 5 known congeners were isolated from the barks of Salix tetrasperma, and their structures were elucidated by spectroscopic analyses, single-crystal X-ray diffraction, electronic circular dichroism (ECD) calculations, and chemical conversions. Compounds 4-6 significantly inhibited NO production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages, and the most active 4 obviously suppressed the production of IL-1ß and IL-6 and decreased iNOS and COX-2 expression in a dose-dependent manner. Further Western blotting analysis revealed that the anti-inflammatory mechanism of 4 is possibly mediated through the MAPK and NF-κB signaling pathways.

14.
Nat Prod Rep ; 41(7): 1152-1179, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38482919

RESUMO

Covering: up to the end of 2023Cephalotane diterpenoids are a unique class of natural products exclusive to the genus Cephalotaxus, featuring a rigid 7,6,5,6-fused tetracyclic architecture. The study of cephalotanes dates back to the 1970s, when harringtonolide (1), a Cephalotaxus troponoid with a peculiar norditerpenoid carbon skeleton, was first discovered. In recent years, prototype C20 diterpenoids proposed as cephalotane were disclosed, which triggered intense studies on this diterpenoid family. To date, a cumulative total of 105 cephalotane diterpenoids with great structural diversity and biological importance have been isolated. In addition, significant advances have been made in the field of total synthesis and biosynthesis of cephalotanes in recent years. This review provides a complete overview of the chemical structures, bioactivities, biosynthetic aspects, and completed total synthesis of all the isolated cephalotane diterpenoids, which will help guide future research on this class of compounds.


Assuntos
Produtos Biológicos , Diterpenos , Diterpenos/química , Diterpenos/farmacologia , Diterpenos/metabolismo , Estrutura Molecular , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Produtos Biológicos/metabolismo , Cephalotaxus/química , Cephalotaxus/metabolismo
15.
Mitochondrial DNA B Resour ; 9(3): 322-326, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476835

RESUMO

Dianella ensifolia (L.) Redouté 1802 is a plant known for its significant medicinal values. In this study, we presented its chloroplast genome. The length of the chloroplast genome was found to be 156,571 bp, with a GC content of 37.86%. It consisted of a large single-copy (LSC) of 85,318 bp and a small single-copy (SSC) of 18,307 bp, a pair of inverted repeats (IRs) of 26,473 bp each that separated the LSC and SSC regions. The chloroplast genome of D. ensifolia consisted of 114 unique genes, including 80 protein-coding genes, four rRNA genes, and 30 tRNA genes. Through phylogenetic analysis, we identified a close relationship between D. ensifolia and D. nigra. This newly sequenced chloroplast genome not only enhances our understanding of the genome of Dianella, but also provides valuable insights for the evolutionary study of the family Asphodelaceae.

16.
BMC Pulm Med ; 24(1): 144, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509541

RESUMO

BACKGROUND: The causality of the relationship between bronchiectasis and chronic obstructive pulmonary disease (COPD) remains unclear. This study aims to investigate the potential causal relationship between them, with a specific focus on the role of airway inflammation, infections, smoking as the mediators in the development of COPD. METHODS: We conducted a two-sample Mendelian randomization (MR) analysis to assess: (1) the causal impact of bronchiectasis on COPD, sex, smoking status, infections, eosinophil and neutrophil counts, as well as the causal impact of COPD on bronchiectasis; (2) the causal effect of smoking status, infections and neutrophil counts on COPD; and (3) the extent to which the smoking status, infections and neutrophil counts might mediate any influence of bronchiectasis on the development of COPD. RESULTS: COPD was associated with a higher risk of bronchiectasis (OR 1.28 [95% CI 1.05, 1.56]). Bronchiectasis was associated with a higher risk of COPD (OR 1.08 [95% CI 1.04, 1.13]), higher levels of neutrophil (OR 1.01 [95% CI 1.00, 1.01]), higher risk of respiratory infections (OR 1.04 [95% CI 1.02, 1.06]) and lower risk of smoking. The causal associations of higher neutrophil cells, respiratory infections and smoking with higher COPD risk remained after performing sensitivity analyses that considered different models of horizontal pleiotropy, with OR 1.17, 1.69 and 95.13, respectively. The bronchiectasis-COPD effect was 0.99, 0.85 and 122.79 with genetic adjustment for neutrophils, respiratory infections and smoking. CONCLUSION: COPD and bronchiectasis are mutually causal. And increased neutrophil cell count and respiratory infections appears to mediate much of the effect of bronchiectasis on COPD.


Assuntos
Bronquiectasia , Doença Pulmonar Obstrutiva Crônica , Infecções Respiratórias , Humanos , Neutrófilos , Fumar/efeitos adversos , Fumar/epidemiologia , Análise da Randomização Mendeliana , Bronquiectasia/complicações , Infecções Respiratórias/complicações , Estudo de Associação Genômica Ampla
17.
J Med Chem ; 67(6): 4560-4582, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38502936

RESUMO

Inspired by the structure of dysoxylactam A (DLA) that has been demonstrated to reverse P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) effectively, 61 structurally simplified cyclolipopeptides were thus designed and synthesized via an effective method, and their reversing P-gp-mediated MDR potentials were evaluated, which provided a series of more potent analogues and allowed us to explore their structure-activity relationship (SAR). Among them, a well-simplified compound, 56, with only two chiral centers that all derived from amino acids dramatically reversed drug resistance in KBV200 cells at 10 µM in combination with vinorelbine (VNR), paclitaxel (PTX), and adriamycin (ADR), respectively, which is more promising than DLA. The mechanism study showed that 56 reversed the MDR of tumor cells by inhibiting the transport function of P-gp rather than reducing its expression. Notably, compound 56 effectively restored the sensitivity of MDR tumors to VNR in vivo at a dosage without obvious toxicity.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Resistencia a Medicamentos Antineoplásicos , Lipopeptídeos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Resistência a Múltiplos Medicamentos , Subfamília B de Transportador de Cassetes de Ligação de ATP , Doxorrubicina/farmacologia , Linhagem Celular Tumoral
18.
World J Clin Cases ; 12(4): 681-687, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38322690

RESUMO

Although the pediatric perioperative pain management has been improved in recent years, the valid and reliable pain assessment tool in perioperative period of children remains a challenging task. Pediatric perioperative pain management is intractable not only because children cannot express their emotions accurately and objectively due to their inability to describe physiological characteristics of feeling which are different from those of adults, but also because there is a lack of effective and specific assessment tool for children. In addition, exposure to repeated painful stimuli early in life is known to have short and long-term adverse sequelae. The short-term sequelae can induce a series of neurological, endocrine, cardiovascular system stress related to psychological trauma, while long-term sequelae may alter brain maturation process, which can lead to impair neurodevelopmental, behavioral, and cognitive function. Children's facial expressions largely reflect the degree of pain, which has led to the developing of a number of pain scoring tools that will help improve the quality of pain management in children if they are continually studied in depth. The artificial intelligence (AI) technology represented by machine learning has reached an unprecedented level in image processing of deep facial models through deep convolutional neural networks, which can effectively identify and systematically analyze various subtle features of children's facial expressions. Based on the construction of a large database of images of facial expressions in children with perioperative pain, this study proposes to develop and apply automatic facial pain expression recognition software using AI technology. The study aims to improve the postoperative pain management for pediatric population and the short-term and long-term quality of life for pediatric patients after operational event.

19.
Bioorg Chem ; 145: 107194, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38367429

RESUMO

Phytochemical investigation into the medium polar fraction of the ethanol extract of Euphorbia peplus led to the identification of 32 diterpenoids with five structural types. Compounds 1-5 and 7-11 are reported for the first time, while the configuration of 6,7-epoxy group of 6 was revised to be ß-oriented. Compounds 1-5 feature a rare structural variation of the double bond at Δ1 migrating to Δ1(10) in the tigliane-type diterpenoid family. Biologically, compound 21 was found to be the only one to show moderate cytotoxic activity, associated with the presence of a benzoyloxy residue at C-16. Besides, compounds 4, 8, 12, 13, 16, and 19 show significant inhibitory activities against NO production induced by LPS in RAW264.7 macrophage cells, with IC50 values within 2-5 µM. Structure-activity relationship (SAR) analysis revealed that the ingenane-type diterpenoids have the best anti-inflammatory activity, and the esterification at 3-OH or 5-OH is crucial. Further biological researches demonstrated that 13, the predominant metabolite in this plant, exerts anti-inflammatory effects by blocking the activation of NF-κB and MAPK signaling pathways.


Assuntos
Antineoplásicos , Diterpenos , Euphorbia , Diterpenos/farmacologia , Diterpenos/química , Relação Estrutura-Atividade , Euphorbia/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Antineoplásicos/farmacologia , Estrutura Molecular
20.
Chem Biodivers ; 21(4): e202400256, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38361228

RESUMO

The plant species, Sonchus wightianus DC., was historically used in China for both medicinal and dietary uses. In present study, seven new guaiane sesquiterpenoids (1-7) and one cytochalasin (8), along with five known guaianes (9-13) and two known cytochalasins (14 and 15), were isolated from the whole plants of S. wightianus. These guaianes showed structural variations in the substituents at C-8 and/or C-15, and compounds 6 and 7 are two sesquiterpenoid glycoside derivatives. Their structures were determined by extensive analysis of spectroscopic, electronic circular dichroism, and X-ray diffraction data, and chemical method. Biological tests revealed that compounds 5 and 8 are potent and selective immunosuppressive reagents.


Assuntos
Sesquiterpenos , Sonchus , Citocalasinas/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Difração de Raios X , China , Estrutura Molecular
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