RESUMO
Guided by the Global Natural Products Social (GNPS) molecular networking strategy, five undescribed eremophilane-type sesquiterpenoid derivatives (1-5) were isolated and identified from fungus Penicillium roqueforti, which was separated from the root soil of plant Hypericum beanii collected in Shennongjia Forestry District, Hubei Province. Dipeniroqueforins A-B (1-2), representing a lactam-type sesquiterpenoid skeleton with a highly symmetrical and homodimeric 5/6/6-6/6/5 hexacyclic system, are reported within the eremophilane-type family for the first time. Peniroqueforin D (5) represents the first example of a 1,2-seco eremophilane-type sesquiterpenoid derivative featuring an undescribed 7/6-fused ring system. The structures of these compounds were elucidated by various spectroscopic analyses, DP4+ probability analyses, ECD calculations, and single-crystal X-ray diffraction experiments. Furthermore, these isolates were evaluated for cytotoxicity, and the result uncovered that compound 1 displayed broad-spectrum activity. Further mechanistic study revealed that compound 1 could significantly upregulate the mRNA expression of genes related to the oxidative induction, leading to the abnormal ROS levels in tumor cells and ultimately causing tumor cell apoptosis.
Assuntos
Antineoplásicos , Penicillium , Sesquiterpenos , Sesquiterpenos Policíclicos , Estrutura Molecular , Sesquiterpenos/química , Penicillium/química , Antineoplásicos/químicaRESUMO
By co-culturing two endophytic fungi (Chaetomium virescens and Xylaria grammica) collected from the medicinal and edible plant Smilax glabra Roxb. and analyzing them with MolNetEnhancer module on GNPS platform, seven undescribed chromone-derived polyketides (chaetoxylariones A-G), including three pairs of enantiomer ones (2a/2b, 4a/4b and 6a/6b) and four optical pure ones (1, 3, 5 and 7), as well as five known structural analogues (8-12), were obtained. The structures of these new compounds were characterized by NMR spectroscopy, single-crystal X-ray diffraction, 13C NMR calculation and DP4+ probability analyses, as well as the comparison of the experimental electronic circular dichroism (ECD) data. Structurally, compound 1 featured an unprecedented chromone-derived sulfonamide tailored by two isoleucine-derived δ-hydroxy-3-methylpentenoic acids via the acylamide and NO bonds, respectively; compound 2 represented the first example of enantiomeric chromone derivative bearing a unique spiro-[3.3]alkane ring system; compound 3 featured a decane alkyl side chain that formed an undescribed five-membered lactone ring between C-7' and C-10'; compound 4 contained an unexpected highly oxidized five-membered carbocyclic system featuring rare adjacent keto groups; compound 7 featured a rare methylsulfonyl moiety. In addition, compound 10 showed a significant inhibition towards SW620/AD300 cells with an IC50 value of PTX significantly decreased from 4.09 µM to 120 nM, and a further study uncovered that compound 10 could obviously reverse the MDR of SW620/AD300 cells.
Assuntos
Antineoplásicos , Chaetomium , Cromonas , Ensaios de Seleção de Medicamentos Antitumorais , Policetídeos , Xylariales , Cromonas/química , Cromonas/farmacologia , Cromonas/isolamento & purificação , Policetídeos/química , Policetídeos/farmacologia , Policetídeos/isolamento & purificação , Estrutura Molecular , Xylariales/química , Chaetomium/química , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Linhagem Celular Tumoral , Técnicas de Cocultura , Proliferação de Células/efeitos dos fármacosRESUMO
Intestinal diseases have always posed a serious threat to human health, with inflammatory bowel disease (IBD) being one of them. IBD is an autoimmune disease characterized by chronic inflammation, including ulcerative colitis (UC) and Crohn's disease (CD). The "alarm" cytokine IL-33, which is intimately associated with Th2 immunity, is a highly potent inflammatory factor that is considered to have dual functions-operating as both a pro-inflammatory cytokine and a transcriptional regulator. IL-33 has been shown to play a crucial role in both the onset and development of IBD. Therefore, this review focuses on the pathogenesis of IBD, the major receptor cell types, and the activities of IL-33 in innate and adaptive immunity, as well as its underlying mechanisms and conflicting conclusions in IBD. We have also summarized different medicines targeted to IL-33-associated diseases. Furthermore, we have emphasized the role of IL-33 in gastrointestinal cancer and parasitic infections, giving novel prospective therapeutic utility in the future application of IL-33.
Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Citocinas , Doenças Inflamatórias Intestinais/tratamento farmacológico , Interleucina-33RESUMO
Background: Glioma is one of the most malignant and aggressive tumors, with an extremely poor prognosis. Human telomerase reverse transcriptase (hTERT) promoter mutation is regarded as a risk factor in tumor growth. Although the prevalence of hTERT promoter (pTERT) mutation in gliomas has been investigated, the results are inconsistent. This meta-analysis aims to investigate the prognostic value of hTERT in glioma patients and its interaction with other biomarkers. Materials and Methods: We searched 244 citations from four databases: PubMed (2000-2021), Web of Science (2000-2021), Embase (2010-2021), and Cochrane Library (2000-2021) with 28 articles included. Results: We calculated hazard ratios (HRs) using the random effect model and the pooled result suggested that TERT promoter mutation predicted poorer overall survival (HR: 1.53, 95% confidence interval [CI]: 1.34-1.75, P < 0.001, I2: 49.9%, pheterogeneity:0.002) and progression-free survival (HR: 1.55, 95% CI: 1.27-1.88, P < 0.001, I2: 0.0%, pheterogeneity: 0.473). For subgroup analysis, we analyzed multiple factors including iso-citrate dehydrogenase (IDH) genotype, age, diagnosis, pTERT region, so as to locate the sources of heterogeneity. Interestingly, in IDH mutant subgroup, pTERT mutation became a beneficial prognostic factor (HR: 0.73, 95% CI: 0.57-0.93, I2: 22.3%, pheterogeneity: 0.277), which is contrary to the results in pooled analysis. Conclusion: In general, pTERT mutation may result in shorter survival time in glioma patients, but longer survival time when glioma patients are combined with IDH mutation.
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Fifteen secondary metabolites, including five new sesquiterpenoids (1-5), one new benzofuranoid (10), one new ophiobolin sesterterpenoid (11), and one new 3,5-dimethylorsellinic acid (DMOA)-based meroterpenoid (15), as well as seven known analogues (6-9 and 12-14), were isolated and characterized from fungus Aspergillus calidoustus, which was separated from the wetland soil collected at Dianchi Lake, Yunnan Province. Compound 5 featured an unusual dioxolane moiety, and compound 15 was a rare austin meroterpenoid analogue with the opened A ring, and also featured an undescribed oxygen bridge between C-3 and C-16 to construct an unexpected tetrahydrofuran ring. Their structures were established by widespread spectroscopic methods, single-crystal X-ray diffraction experiments, and ECD calculation. All the isolated drimane sesquiterpenoids were evaluated for the in vitro cytotoxicity against five tumor cell lines, including SW480 (colon cancer), IOMM-Lee (meningioma), HeLa (cervical cancer), FARAGE (diffuse large B-cell lymphoma), and SU-DHL-4 (diffuse large B-cell lymphoma). Compound 9 exhibited significant cytotoxicity against FARAGE and SU-DHL-4 tumor cell lines with IC50 values of 5.54 and 9.78 µM, respectively. Further mechanism study showed that 9 could significantly promote apoptosis in FARAGE and SU-DHL-4 cell lines by interfering with mitochondrial function.
Assuntos
Linfoma Difuso de Grandes Células B , Sesquiterpenos , Aspergillus , China , Fungos , Humanos , Estrutura Molecular , Sesquiterpenos/química , SoloRESUMO
Coculturing two or more fungi is a useful strategy to awaken the silent genes to produce structurally diverse and bioactive natural products. Through the coculture of Pestalotiopsis sp. and Penicillium bialowiezense, six new isoprenylated chromane derivatives, including two pairs of enantiomeric ones (1a/1b-2a/2b) and two optical pure ones (3-4), two new isoprenylated phenol glucoside derivatives (6-7), as well as eight known structural analogues (5 and 8-14), were obtained. The structures of these new compounds were characterized by NMR spectroscopy, single-crystal X-ray crystallography, and ECD calculation. The Δ10,11 double bond of pestaloficin D (5) was revised to E-configurated based on the extensive spectroscopic analyses. Compounds 1a/1b and 2a/2b were the first examples of enantiomeric isoprenylated chromane derivatives, which were successfully separated by chiral HPLC. Additionally, all the isolated compounds were evaluated for the in vitro ß-glucuronidase (GUS) and butyrylcholinesterase (BChE) inhibitory activities. Compounds 1a and 1b showed significant ß-glucuronidase inhibitory potency with IC50 values of 7.6 and 10.3 µM, respectively. Compound 14 exhibited moderate BChE inhibitory activity with an IC50 value of 21.3 µM. In addition, the structure-enzyme inhibitory activity relationship of compounds 1-14 is discussed.
Assuntos
Butirilcolinesterase/metabolismo , Cromanos/farmacologia , Inibidores Enzimáticos/farmacologia , Glucuronidase/antagonistas & inibidores , Penicillium/química , Pestalotiopsis/química , Animais , Bactérias/enzimologia , Cromanos/química , Cromanos/metabolismo , Cristalografia por Raios X , Teoria da Densidade Funcional , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Glucuronidase/metabolismo , Cavalos , Modelos Moleculares , Estrutura Molecular , Penicillium/metabolismo , Pestalotiopsis/metabolismoRESUMO
Three pairs of undescribed enantiomeric α-pyrone derivatives (1a/1b-3a/3b) and six undescribed congeners (4-9), were obtained from the fungus Alternaria brassicicola that was isolated from the fresh leaves of Siegesbeckia pubescens Makino (Compositae). The structures of these new compounds were characterized by extensive NMR spectroscopic and HRESIMS data, and their absolute configurations were further elucidated by a modified Mosher's method, chemical conversion, single-crystal X-ray diffraction analysis, and ECD calculations. This is the first report of three pairs of enantiomeric α-pyrone derivatives from the fungus A. brassicicola, and these enantiomers were successfully acquired from scalemic mixtures via chiral HPLC. Compounds 1a/1b-3a/3b and 4-9 were evaluated for the herbicidal activity against Echinochloa crusgalli, Setaria viridis, Portulaca oleracea, and Taraxacum mongolicum. At a concentration of 100 µg/mL, compounds 1a and 1b could significantly inhibit the germination of monocotyledon weed seeds (E. crusgalli and S. viridis) with inhibitory ratios ranging from 68.6 ± 6.4% to 84.2 ± 5.1%, which was equivalent to that of the positive control (glyphosate). The potential structure-herbicidal activity relationship of these compounds was also discussed. To a certain extent, the results of this study will attract great interest for the potential practical application of promising fungal metabolites, α-pyrone derivatives, as ecofriendly herbicides.
Assuntos
Alternaria/química , Herbicidas/farmacologia , Pironas/farmacologia , Asteraceae/química , Relação Dose-Resposta a Droga , Echinochloa/efeitos dos fármacos , Herbicidas/química , Herbicidas/isolamento & purificação , Estrutura Molecular , Portulaca/efeitos dos fármacos , Pironas/química , Pironas/isolamento & purificação , Setaria (Planta)/efeitos dos fármacos , Relação Estrutura-Atividade , Taraxacum/efeitos dos fármacosRESUMO
Bioassay-directed isolation of secondary metabolites from an extract of Penicillium chrysogenum TJ403-CA4 isolated from the medicinally valuable arthropod Cryptotympana atrata afforded five new and 10 known compounds (1-15). All the compounds (except 14) belong to a minor class of highly rigid 6-5-5-5-fused tetracyclic cyclopiane-type diterpenes known to be exclusively produced by members of the Penicillium genus. The structures and absolute configurations of the new compounds (1-5) were elucidated by extensive spectroscopic analyses, including HRESIMS and 1D and 2D NMR, single-crystal X-ray diffraction, and comparison of the experimental electronic circular dichroism data. Compounds 1 and 2 represent the first examples of cyclopianes bearing a C-20 carboxyl group; compound 3 represents the first example of a cyclopiane with a gem-hydroxymethyl group; compound 4 represents the second example of a cyclopiane bearing a hydroxy group at C-7; compound 5 represents the first example of a cyclopiane bearing a hydroxy group at C-8. Compounds 2 and 3 exhibited activity against MRSA, with MIC values of 4.0 and 2.0 µg/mL, respectively. In addition, the structure-antibacterial activity relationship (SAR) of compounds 1-15 is discussed.
Assuntos
Antibacterianos/farmacologia , Artrópodes/metabolismo , Bioensaio/métodos , Penicillium chrysogenum/metabolismo , Animais , Antibacterianos/química , Cristalografia por Raios X , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Análise Espectral/métodos , Relação Estrutura-AtividadeRESUMO
The reported fumiquinazoline-related alkaloids cottoquinazolines E-G (1-3) were reisolated from solid cultures of the fungus Neosartorya fischeri, which was isolated from the medicinal arthropod Cryptotympana atrata. The unresolved issues regarding the absolute configurations (for cottoquinazolines E and F) prompted a reinvestigation of the configurations for all three compounds, as enabled by extensive spectroscopic methods, comparisons of experimental electronic circular dichroism data, and X-ray crystallography. In addition, cottoquinazoline F (2) showed significant antibacterial activity against ESBL-producing Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterococcus faecalis with MIC values of 8, 32, 32, and 16 µg/mL, respectively.
Assuntos
Alcaloides/farmacologia , Antibacterianos/farmacologia , Artrópodes/química , Aspergillus/química , Enterococcus faecalis/química , Fungos/química , Pseudomonas aeruginosa/química , Quinazolinas/farmacologia , Alcaloides/química , Animais , Antibacterianos/química , Dicroísmo Circular , Cristalografia por Raios X , Estrutura Molecular , Quinazolinas/químicaRESUMO
Seven new modified fusicoccane-type diterpenoids (1-7), together with two known congeners (8 and 9), were obtained from Alternaria brassicicola. Their structures were elucidated from a combination of NMR and HRESIMS data and 13C NMR calculation as well as DP4+ probability analyses, and the absolute configurations of 1-5 were determined by ECD calculation and single-crystal X-ray diffraction (Cu Kα). Compounds 1-3 belong to a rare class of 16-nor-dicyclopenta[a,d]cyclooctane diterpenoids, and compounds 2 and 4 represent the first examples of fusicoccane-type diterpenoids featuring two previously undescribed tetracyclic 5/6/6/5 ring systems, while compound 5 features a previously undescribed tetracyclic 5/8/5/3 ring system. Compound 7 was moderately anti-inflammatory, and compounds 2, 3, 5, and 7 were weakly cytotoxic.
Assuntos
Alternaria/química , Diterpenos/química , Animais , Anti-Inflamatórios/farmacologia , Antibióticos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Diterpenos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Células RAW 264.7 , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Fusicoccane-derived diterpenoids bearing a unique bridgehead double-bond-containing tricyclo[9.2.1.03,7]tetradecane (5-9-5 ring system) core skeleton represent a rarely reported class of rearranged terpenoids, which traced back to fusicoccanes with a classical dicyclopenta[a,d]cyclooctane (5-8-5 ring system) core skeleton via a crucial Wagner-Meerwein rearrangement reaction. In this research, alterbrassicenes B-D (1-3), three new rearranged fusicoccane diterpenoids bearing a rare bridgehead double-bond-containing tricyclo[9.2.1.03,7]tetradecane core skeleton, together with two known congeners, brassicicenes O and K (4 and 5), were isolated from the modified cultures of fungus Alternaria brassicicola. Their structures were elucidated by comprehensive analyses of the NMR and HRESIMS data, and the absolute configurations of 1 and 4 were further confirmed via a combination of 13C NMR and ECD calculations and single-crystal X-ray diffraction analysis (Cu Kα). Interestingly, alterbrassicene B (1) represented the second case of bridgehead C-10-C-11 double-bond-containing natural products with a bicyclo[6.2.1]undecane core skeleton, and also featured an undescribed oxygen bridge between C-6 and C-14 to construct an unprecedentedly caged tetracyclic system. Alterbrassicenes B-D showed moderate cytotoxic activity against certain human tumor cell lines with IC50 values in the range of 15.87-36.85 µM.
Assuntos
Alcanos/química , Alternaria/química , Antineoplásicos/química , Diterpenos/química , Alcanos/isolamento & purificação , Alcanos/farmacologia , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Humanos , Modelos Moleculares , Neoplasias/tratamento farmacológico , Compostos Policíclicos/química , Compostos Policíclicos/isolamento & purificação , Compostos Policíclicos/farmacologiaRESUMO
Seven previously undescribed metabolites, designated as tricycloalternarenes Q-W (1-7), were isolated and identified from the fermented rice substrate of fungus Alternaria brassicicola. The planar and absolute structures of all new compounds were determined on the basis of extensive NMR spectroscopic data, a modified Mosher's method, X-ray crystallographic analysis, and electronic circular dichroism (ECD) spectral analyses. All the isolates were evaluated for in vitro cytotoxicity against five human tumor MM231, MM468, HeLa, SW1990, and SW480 cell lines, and compounds 1, 2, 5, and 7 showed selective cytotoxicity against certain human tumor cell lines with IC50 values ranging from 12.83 to 32.87⯵M, with no obvious cytotoxicity to the normal LO2 cell.
Assuntos
Alternaria/química , Antineoplásicos/farmacologia , Terpenos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade , Terpenos/química , Terpenos/isolamento & purificaçãoRESUMO
Altering the cultivation conditions, such as temperature, media compositions, illumination, aeration, the shape of the culturing flask, etc., is regarded as a useful strategy for the exploitation of structurally novel and bioactive secondary metabolites, which inspired us to explore the chemical and pharmacological diversities from the genetically powerful fungus Alternaria brassicicola. As a result, twelve fusicoccane-type diterpenoids, including eight new ones, termed brassicicenes Q-X (1-8), were isolated from a modified rice medium. Biosynthetically, all these compounds were derived from the mevalonic acid (MVA) pathway, and their structures incorporating absolute configurations were assigned by the interpretation of spectroscopic (HRESIMS and 1D and 2D NMR) analyses, chemical conversion, a modified Mosher's method, 13C NMR calculation, and single-crystal X-ray diffraction (Cu Kα). Structurally, compound 1 was an unusual 16-nor-dicyclopenta[a,d]cyclooctane diterpenoid bearing a fused cyclopent-2-en-1-one moiety. In addition, compound 3 was found to show significant anti-inflammatory activity against the production of NO, TNF-α, and IL-1ß at 10 µM. Further western blot and immunofluorescence experiments found the mechanism of action to be that 3 inhibited the NF-κB-activated pathway, highlighting it as a promising starting point for the development of new anti-inflammatory agents.
Assuntos
Alternaria/química , Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Animais , Anti-Inflamatórios/química , Diterpenos/química , Relação Dose-Resposta a Droga , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Camundongos , Modelos Moleculares , Conformação Molecular , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Fator de Transcrição RelA/metabolismoRESUMO
BACKGROUND: A variety of analytical techniques were applied to explore the effects of pulsed electric field (PEF) on α-helix structural changes in the novel antioxidant peptide Lys-Cys-His-Lys-Pro (KCHKP, 611.76 Da). RESULTS: The relative α-helix content of the KCHKP peptide was significantly altered from 100% to 89.91 ± 0.97% when the electric pulse frequency was 1800 Hz and the field intensity was 10 kV cm-1 . Moreover, the 1,1-diphenyl-2-pycryl-hydrazyl (DPPH) and 2,2-azinobis diammonium salt (ABTS) radical-scavenging activities of PEF-treated KCHKP were increased from 56.31% ± 0.74% to 84.33% ± 1.23% and from 40.56% ± 0.78% to 51.33% ± 0.27%, respectively. CONCLUSION: PEF treatment increased peptide linkage stretch vibration and altered hydrogen bonding of KCHKP. The stability of the α-helix structure was influenced by hydrogen bonds within the peptide linkage of KCHKP induced by PEF and was related to changes in antioxidant activity. © 2017 Society of Chemical Industry.
Assuntos
Nozes/química , Peptídeos/química , Pinus/química , Proteínas de Plantas/química , Técnicas Eletroquímicas , Dobramento de Proteína , Desdobramento de Proteína , Sementes/químicaRESUMO
Granular hydrogels have emerged as a new class of materials for 3D printing, tissue engineering, and food applications due to their extrudability, porosity, and modularity. This work introduces a convenient method to prepare granular hydrogel with tunable properties by modulating the interaction between gum Arabic (GA) and whey protein isolate (WPI) microgels. As the concentration of GA increased, the appearance of the hydrogel changed from fluid liquid to moldable solid, and the microstructure changed from a macro-porous structure with thin walls to a dense structure formed by the accumulation of spherical particles. At a GA concentration of 0.5 %, the hydrogels remained fluid. Granular hydrogels containing 1.0 % GA showed mechanical properties similar to those of tofu (compressive strength: 10.8 ± 0.5 kPa, Young's modulus: 16.7 ± 0.4 kPa), while granular hydrogels containing 1.5 % GA showed mechanical properties similar to those of hawthorn sticks and sausages (compressive strength: 300.4 ± 5.8 kPa; Young's modulus: 200.5 ± 3.4 kPa). The hydrogel with 2.0 % GA was similar to hawthorn sticks, with satisfactory bite resistance and elasticity. Such tunability has led to various application potentials in the food industry to meet consumer demand for healthy, nutritious, and diverse textures.
Assuntos
Goma Arábica , Hidrogéis , Microgéis , Proteínas do Soro do Leite , Goma Arábica/química , Hidrogéis/química , Proteínas do Soro do Leite/química , Microgéis/química , Módulo de Elasticidade , Reologia , Porosidade , Força CompressivaRESUMO
Zinc-ion batteries show great potential as the next-generation power source due to their nontoxic, low-cost, and safe properties. However, issues with zinc anodes, such as dendrite growth and parasitic hydrogen evolution reactions (HERs), must be addressed to commercialize them. Solutions, such as quasi-solid-state electrolytes made from synthetic polymer hydrogels, have been proposed to improve battery flexibility and energy density. However, most polymers used are nonbiodegradable, posing a challenge to sustainability. In this study, hydrogels made from biodegradable poly(vinyl alcohol) and protein nanofibrils from pea protein, a renewable plant-based source, are used as an electrolyte in aqueous zinc-ion batteries. Results show that the flexible and biodegradable hydrogel can enhance the zinc anode stability and effectively restrict HER. This phenomenon is because of the hydrogen-bond network between nanofibril functional groups and water molecules. In addition, the interaction between functional groups on nanofibrils and Zn2+ constructs ion channels for the even migration of Zn2+, avoiding dendrite growth. The Zn||Zn symmetric cell using the hydrogel electrolyte exhibits a long lifespan of over 3000 h and improved capacity retention in the Zn||AC-I2 hybrid ion batteries by suppressing cathode material dissolution. This study suggests the potential of biodegradable hydrogels as a sustainable and effective solution for biodegradable soft powering sources.
Assuntos
Hidrogéis , Proteínas de Ervilha , Zinco , Hidrogênio , Polímeros , ÁguaRESUMO
Three new amide derivatives (alteralkaloids A-C, 1-3) and three known alkaloids (4-6) were afforded after phytochemical investigation of fungus Alternaria brassicicola. The structures of these compounds were confirmed by NMR spectroscopic and HRESIMS data. Furthermore, the absolute configuration of 1 was determined using the single-crystal X-ray diffraction analysis. Compounds 1-3 belong to a class of amide derivatives that have not been found in nature before, sharing the same characteristic signals of the butyl moiety and amide group. These isolated compounds mentioned above were tested for the cytotoxic activity.
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Nine undescribed eremophilane sesquiterpenes, one undescribed guaiane sesquiterpene, along with ten known analogues were isolated and identified from fungus Penicillium roqueforti, which was separated from the root soil of Hypericum beanii N. Robson collected from the Shennongjia Forestry District, Hubei Province. Their structures were elucidated on the basis of various spectroscopic analyses, mainly including NMR and HRESIMS data, 13C NMR calculations with DP4+ probability analyses, ECD calculations, and single-crystal X-ray diffraction experiments. Furthermore, all twenty compounds were evaluated for the in vitro cytotoxic activities against seven human tumor cell lines, and the result suggested that 14-hydroxymethylene-1(10)-ene-epi-guaidiol A exhibited considerable cytotoxic activity against the Farage (IC50 < 10 µM, 48 h), SU-DHL-2, and HL-60 cells. Further mechanism study demonstrated that 14-hydroxymethylene-1(10)-ene-epi-guaidiol A could significantly promote apoptosis by inhibiting tumor cell respiration and decreasing intracellular ROS levels, thereby inducing S-phase blockade in tumor cells.
Assuntos
Penicillium , Sesquiterpenos , Humanos , Sesquiterpenos Policíclicos , Sesquiterpenos de Guaiano , Estrutura Molecular , Sesquiterpenos/química , Penicillium/químicaRESUMO
Plasmacytoid dendritic cells (pDCs), a subtype of DC, possess unique developmental, morphological, and functional traits that have sparked much debate over the years whether they should be categorized as DCs. The digestive system has the greatest mucosal tissue overall, and the pDC therein is responsible for shaping the adaptive and innate immunity of the gastrointestinal tract, resisting pathogen invasion through generating type I interferons, presenting antigens, and participating in immunological responses. Therefore, its alleged importance in the gut has received a lot of attention in recent years, and a fresh functional overview is still required. Here, we summarize the current understanding of mouse and human pDCs, ranging from their formation and different qualities compared with related cell types to their functional characteristics in intestinal disorders, including colon cancer, infections, autoimmune diseases, and intestinal graft-versus-host disease. The purpose of this review is to convey our insights, demonstrate the limits of existing research, and lay a theoretical foundation for the rational development and use of pDCs in future clinical practice.
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Through multiple different pathways, the environmental multiple metals make their ways to the human bodies, where they induce different levels of the oxidative stress response. This study further investigated the impact of multiple-metal exposure on the risk of developing proliferative diabetic retinopathy (PDR). We designed a case-control study with type 2 diabetic patients (T2D), in which the case group was the proliferative diabetic retinopathy group (PDR group), while the control group was the non-diabetic retinopathy group (NDR group). Graphite furnace atomic absorption spectrometry (GFAAS) and inductively coupled plasma optical emission spectrometry (ICP-OES) were used to detect the metal levels in our participants' urine samples. The least absolute shrinkage and selection operator (LASSO) regression approach was used to include these representative trace elements in a multiple exposure model. Following that, logistic regression models and Bayesian kernel machine regression (BKMR) models were used to describe the effect of different elements and also analyze their combined effect. In the single-element model, we discovered that lithium (Li), cadmium (Cd), and strontium (Sr) were all positively related to PDR. The multiple-exposure model revealed a positive relationship between Li and PDR risk, with a maximum quartile OR of 2.80 (95% CI: 1.10-7.16). The BKMR model also revealed that selenium (Se) might act as a protective agent, whereas magnesium (Mg), Li, and Cd may raise the risk of PDR. In conclusion, our study not only revealed an association between exposure to multiple metals and PDR risk but it also implied that urine samples might be a useful tool to assess PDR risk.