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1.
Pest Manag Sci ; 80(6): 3022-3034, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38318944

RESUMO

BACKGROUND: Citrus canker caused by Xanthomonas citri subsp. citri (Xcc) is a devastating bacterial disease that reduces citrus yield and quality, posing a serious threat to the citrus industry. Several conventional chemicals have been used to control citrus canker. However, this approach often leads to the excessive use of chemical agents, can exacerbate environmental pollution and promotes the development of resistant Xcc. Therefore, there is significant interest in the development of efficient and environmentally friendly technologies to control citrus canker. RESULTS: In this study, water-soluble ZnO quantum dots (ZnO QDs) were synthesised as an efficient nanopesticide against Xcc. The results showed that the antibacterial activity of ZnO QDs irradiated with visible light [half-maximal effective concentration (EC50) = 33.18 µg mL-1] was ~3.5 times higher than that of the dark-treated group (EC50 = 114.80 µg mL-1). ZnO QDs induced the generation of reactive oxygen species (•OH, •O- 2 and 1O2) under light irradiation, resulting in DNA damage, cytoplasmic destruction, and decreased catalase and superoxide dismutase activities. Transcription analysis showed downregulation of Xcc genes related to 'biofilms, virulence, adhesion' and 'DNA transfer' exposure to ZnO QDs. More importantly, ZnO QDs also promoted the growth of citrus. CONCLUSION: This research provides new insights into the photocatalytic antibacterial mechanisms of ZnO QDs and supports the development of more efficient and safer ZnO QDs-based nanopesticides to control citrus canker. © 2024 Society of Chemical Industry.


Assuntos
Citrus , Luz , Doenças das Plantas , Pontos Quânticos , Xanthomonas , Óxido de Zinco , Pontos Quânticos/química , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Xanthomonas/efeitos dos fármacos , Xanthomonas/efeitos da radiação , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Citrus/microbiologia , Antibacterianos/farmacologia
2.
Phytochemistry ; 218: 113956, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38135206

RESUMO

Seventeen undescribed sesquiterpene-alkaloid hybrids (liriogerphines E-U, 1-17) were isolated and identified during a further phytochemical investigation on the branches and leaves of Chinese tulip tree (Liriodendron chinense), a rare medicinal and ornamental plant endemic to China. These unique heterodimers are conjugates of germacranolide-type sesquiterpenoids with structurally diverse alkaloids [i.e., aporphine- (1-15), proaporphine- (16), and benzyltetrahydroisoquinoline-type (17)] via the formation of a C-N bond. The previously undescribed structures were elucidated by comprehensive spectroscopic data analyses and electronic circular dichroism calculations. Such a class of sesquiterpene-alkaloid hybrids presumably biosynthesized via an aza-Michael addition is quite rare from terrestrial plants. In particular, the sesquiterpene-benzyltetrahydroisoquinoline hybrid skeleton has never been reported until the present study. All the isolates were evaluated for their cytotoxic effects against a small panel of leukemia cell lines (Raji, Jeko-1, Daudi, Jurkat, MV-4-11 and HL-60), and some of them exhibited considerable activities.


Assuntos
Alcaloides , Antineoplásicos , Liriodendron , Sesquiterpenos , Liriodendron/química , Alcaloides/química , Folhas de Planta/química , Sesquiterpenos/química , Estrutura Molecular
3.
Front Immunol ; 14: 1149366, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37283763

RESUMO

In adipose tissue, macrophages are the most abundant immune cells with high heterogeneity and plasticity. Depending on environmental cues and molecular mediators, adipose tissue macrophages (ATMs) can be polarized into pro- or anti-inflammatory cells. In the state of obesity, ATMs switch from the M2 polarized state to the M1 state, which contributes to chronic inflammation, thereby promoting the pathogenic progression of obesity and other metabolic diseases. Recent studies show that multiple ATM subpopulations cluster separately from the M1 or M2 polarized state. Various factors are related to ATM polarization, including cytokines, hormones, metabolites and transcription factors. Here, we discuss our current understanding of the potential regulatory mechanisms underlying ATM polarization induced by autocrine and paracrine factors. A better understanding of how ATMs polarize may provide new therapeutic strategies for obesity-related diseases.


Assuntos
Tecido Adiposo , Obesidade , Humanos , Tecido Adiposo/metabolismo , Obesidade/metabolismo , Macrófagos , Citocinas/metabolismo , Fatores de Transcrição/metabolismo
4.
J Nat Prod ; 86(6): 1487-1499, 2023 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-37291059

RESUMO

A preliminary phytochemical investigation on the 90% MeOH extract from the twigs and needles of the vulnerable conifer Keteleeria fortunei led to the isolation and characterization of 17 structurally diverse triterpen-26-oic acids, including nine previously undescribed ones (fortunefuroic acids A-I, 1-9) featuring a rare furoic acid moiety in the lateral chain. Among them, 1-5 are uncommon 9ßH-lanostane-type triterpenoic acids. Friedo-rearranged triterpenoids 6 and 7 feature a unique 17,14-friedo-lanostane skeleton, whereas 9 possesses a rare 17,13-friedo-cycloartane-type framework. Their structures and absolute configurations were elucidated by extensive spectroscopic (e.g., detailed 2D NMR) and computational (NMR/ECD) calculations and the modified Mosher's method. In addition, the absolute structure of compound 1 was ascertained by single-crystal X-ray diffraction analyses. Fortunefuroic acids B (2), G (7), and I (9), along with isomangiferolic acid (12) and 3α,27-dihydroxycycloart-24E-en-26-oic acid (14), exhibited dual inhibitory effects against the adenosine triphosphate (ATP)-citrate lyase (ACL, IC50s: 5.7-11.4 µM) and acetyl-CoA carboxylase 1 (ACC1, IC50s: 7.5-10.5 µM), both of which are key enzymes for glycolipid metabolism. The interactions of the bioactive triterpenoids with both enzymes were examined by molecular docking studies. The above findings reveal the important role of protecting plant species diversity in support of chemical diversity and potential sources of new therapeutics for ACL-/ACC1-associated diseases.


Assuntos
Abies , Traqueófitas , Triterpenos , Simulação de Acoplamento Molecular , Triterpenos/química , Abies/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular
5.
Phytochemistry ; 210: 113663, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36990194

RESUMO

Six undescribed naturally occurring abietane-O-abietane dimers (squamabietenols A-F) together with one 3,4-seco-totarane-type, a pimarane-type, and 17 related known mono-/dimeric diterpenoids were isolated and characterized from the needles and twigs of the ornamental conifer Juniperus squamata. The undescribed structures and their absolute configurations were established by extensive spectroscopic methods, GIAO NMR calculations with DP4+ probability analyses, and ECD calculations. Squamabietenols A and B showed significant inhibitory effects against ATP-citrate lyase (ACL, a novel drug target for hyperlipidemia and other metabolic disorders), with IC50 values of 8.82 and 4.49 µM, respectively. A molecular docking study corroborated the findings by highlighting the interactions between the bioactive compounds and the ACL enzyme (binding affinities: -7.1 to -9.0 kcal/mol). The unique abietane-O-abietane dimeric diterpenoids are quite rare in the vegetable kingdom, and they are of chemotaxonomic significance for the Cupressaceae family.


Assuntos
Diterpenos , Juniperus , Lagartos , Traqueófitas , Animais , Abietanos/química , Simulação de Acoplamento Molecular , Diterpenos/química , Trifosfato de Adenosina , Estrutura Molecular
6.
Cell Death Dis ; 13(12): 1059, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36539410

RESUMO

Epigenetic factor Brd4 has emerged as a key regulator of cancer cell proliferation. Targeted inhibition of Brd4 suppresses growth and induces apoptosis of various cancer cells. In addition to apoptosis, Brd4 has also been shown to regulate several other forms of programmed cell death (PCD), including autophagy, necroptosis, pyroptosis, and ferroptosis, with different biological outcomes. PCD plays key roles in development and tissue homeostasis by eliminating unnecessary or detrimental cells. Dysregulation of PCD is associated with various human diseases, including cancer, neurodegenerative and infectious diseases. In this review, we discussed some recent findings on how Brd4 actively regulates different forms of PCD and the therapeutic potentials of targeting Brd4 in PCD-related human diseases. A better understanding of PCD regulation would provide not only new insights into pathophysiological functions of PCD but also provide new avenues for therapy by targeting Brd4-regulated PCD.


Assuntos
Ferroptose , Neoplasias , Humanos , Proteínas Nucleares/genética , Proteínas Nucleares/uso terapêutico , Fatores de Transcrição/uso terapêutico , Apoptose/fisiologia , Piroptose , Neoplasias/genética , Neoplasias/tratamento farmacológico , Proteínas de Ciclo Celular/genética
7.
Commun Biol ; 5(1): 813, 2022 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-35962126

RESUMO

Staphylococcal aureus (S. aureus) infection can lead to a wide range of diseases such as sepsis and pneumonia. Staphylococcal superantigen-like (SSL) proteins, expressed by all known S. aureus strains, are shown to be involved in immune evasion during S. aureus infection. Here, we show that SSL10, an SSL family protein, exhibits potent cytotoxicity against human cells (HEK293T and HUVEC) by inducing necroptosis upon binding to its receptor TNFR1 on the cell membrane. After binding, two distinct signaling pathways are activated downstream of TNFR1 in a RIPK3-dependent manner, i.e., the RIPK1-RIPK3-MLKL and RIPK3-CaMKII-mitochondrial permeability transition pore (mPTP) pathways. Knockout of ssl10 in S. aureus significantly reduces cytotoxicity of the culture supernatants of S. aureus, indicating that SSL10 is involved in extracellular cytotoxicity during infection. We determined the crystal structure of SSL10 at 1.9 Å resolution and identified a positively charged surface of SSL10 responsible for TNFR1 binding and cytotoxic activity. This study thus provides the description of cytotoxicity through induction of necroptosis by the SSL10 protein, and a potential target for clinical treatment of S. aureus-associated diseases.


Assuntos
Necroptose , Receptores Tipo I de Fatores de Necrose Tumoral , Antígenos de Bactérias , Proteínas de Bactérias , Células HEK293 , Humanos , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Transdução de Sinais , Staphylococcus aureus/metabolismo
8.
Future Oncol ; 18(28): 3179-3190, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35947016

RESUMO

Aim: To explore the possibility of gastric juice (GJ)- and serum-derived SNCG as a potential biomarker for the early diagnosis of gastric cancer (GC). Materials & methods: GJ and serum samples were collected from 87 patients with GC, 38 patients with gastric precancerous lesions and 44 healthy volunteers. The levels of SNCG in GJ and serum samples were detected by ELISA. Results: The levels of SNCG in GJ and serum were significantly higher in the GC group when compared with the GPL group or the control group. The expression of SNCG in GJ and serum was associated with tumor node metastasis stage, lymph node metastasis, tumor size and drinking, and it is important for the diagnosis and prognosis of GC (p < 0.05). Conclusion: The findings highlight the significance of SNCG in GC diagnosis and prognosis and implicate SNCG as a promising candidate for GC treatment.


Gastric cancer (GC) has high morbidity and mortality rates due to its concealment in the early stage. At present, CEA, CA19-9, CA125, CA724, AFP, CA242 and CA50 are commonly used for the diagnosis of GC, but the effects are not satisfactory. Thus, a better biomarker for the diagnosis of GC is required. This study found that SNCG is highly expressed in the gastric juice and serum of GC patients and contributes to GC's progression. Detection of SNCG in gastric juice and serum is an ideal method for early diagnosis of GC with high specificity and sensitivity. Furthermore, SNCG has great value in the prognosis evaluation of GC, and high expression of SNCG predicts shorter survival for patients with GC, which provides a valuable reference for the clinical diagnosis and treatment of GC.


Assuntos
Neoplasias Gástricas , Biomarcadores Tumorais , Detecção Precoce de Câncer , Suco Gástrico/química , Humanos , Proteínas de Neoplasias , Prognóstico , Neoplasias Gástricas/patologia , gama-Sinucleína
9.
J Org Chem ; 87(10): 6927-6933, 2022 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-35512323

RESUMO

Liriogerphines A-D (1-4, respectively), an unprecedented class of hybrids of germacranolide-type sesquiterpenoids and aporphine-type alkaloids, were isolated from the rare medicinal plant Liriodendron chinense. Their structures were elucidated by comprehensive spectroscopic analyses combined with electronic circular dichroism calculations and X-ray crystallographic data. Biosynthetically, an aza-Michael addition reaction is proposed to be involved in the assemblies of this class of hybrids. Compound 4 exhibited cytotoxicity against leukemia cells via inducing apoptosis and inhibiting Bcl-2 expression.


Assuntos
Alcaloides , Antineoplásicos , Liriodendron , Sesquiterpenos , Alcaloides/química , Alcaloides/farmacologia , China , Estrutura Molecular , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Árvores
10.
Bioorg Chem ; 120: 105630, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35091291

RESUMO

The ethanolic extracts of the dried flower buds of two Caprifoliaceae plants, Lonicera japonica and Abelia × grandiflora, showed considerable inhibitory activities against adenosine triphosphate (ATP)-citrate lyase (ACL), a new promising drug target for the treatment of metabolic disorders. Bioassay-guided purification in conjunction with HPLC-PDA profiling led to the isolation and characterization of thirty-five (1-35) and fourteen (1'-14') structurally diverse compounds from the above two plant extracts, respectively. Compounds 1-9 and 1'-6' are previously undescribed glycosides. Their structures were elucidated on the basis of spectroscopic data, electronic circular dichroism (ECD), and single crystal X-ray diffraction analyses. In particular, lonicejaposide A (1) has an unprecedented skeleton generated through the coupling of C-7 in secologanin with C-2'' in phenylacetaldehyde via an aldol condensation. Abeliflorosides A (1') and B (2') are hitherto unknown glycosides of triterpene and bisiridoid conjugates constructed through the formation of a 1,3-dioxane moiety. All the isolates were evaluated for their inhibitory activities against ACL. Compounds 9, 25-28, 31, 1', 2', and 14' displayed significant inhibitory effects, with IC50 values ranging from 0.1 to 14.2 µM. The interactions of selected compounds possessing different structure features (e.g., 9, 25, 31, and 2') with ACL were thereafter performed by employing molecular docking studies. In addition, compound 2', the most complex triterpene-bisiridoid conjugate glycoside reported herein, also inhibited acetyl-CoA carboxylase 1 (ACC1), with an IC50 value of 7.9 µM. The dried material of the flower buds of L. japonica (honeysuckle) is a well-known traditional oriental medicine (i.e., Flos Lonicerae Japonicae, FLJ) and has long been used in large quantities. The above findings not only provide new insights for the development of multipurpose utilization of FLJ in healthcare community, but also provide profitable clues indicating that the flower buds of A. × grandiflora might be a potential alternative to FLJ in the traditional Chinese medicine market.


Assuntos
Caprifoliaceae , Lonicera , Triterpenos , Trifosfato de Adenosina , Flores/química , Glicosídeos/química , Lonicera/química , Simulação de Acoplamento Molecular , Complexos Multienzimáticos , Oxo-Ácido-Liases
11.
Sci Total Environ ; 806(Pt 3): 151300, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34736751

RESUMO

Non-road construction equipment (NRCE) has become a vital contributor to urban air pollutants with the rapid urbanization in China. Black carbon (BC), as a key pollutant emitted from NRCE (mainly diesel-fueled), has attracted considerable concerns due to adverse impacts on climate change, visibility, and human health. However, the understanding of its emissions is still unclear based on limited research results. In this study, we conducted real-world measurements on BC emissions from 12 excavators and 9 loaders to characterize the variation and quantify fuel-based emission factors (EFs) by using a synchronous platform based on PEMS (SP-PEMS). We analyzed the impacts of key factors (operation mode, emission standard, and engine rated power) on BC emission comprehensively. High BC emission in working mode may be mainly owing to the increase of fuel consumption and the deterioration of air-fuel ratio. With more stringent emission standards, BC EFs of all tested NRCE present significant decreasing trends. Interestingly, NRCE with high rated power generally exhibits lower BC emissions. Through comparison, we find BC EFs in this study are generally higher than elemental carbon (EC) EFs reported in previous studies, which will lead BC emissions from NRCE to be underestimated while EC EFs are used instead of BC EFs. Furthermore, BC EFs of NRCE with Stage III are significantly higher (1-3 orders of magnitude) than those of on-road diesel trucks with the current mainstream emission standards of China IV and China V, which reinforces the urgency and importance of controlling BC emissions from NRCE in China. Finally, we recommend BC EFs of excavators and loaders under different emission standards and operation modes, and which preliminarily fills the gap in localized BC EFs of typical NRCE to relieve the urgent needs for emission inventory calculation.


Assuntos
Poluentes Atmosféricos , Emissões de Veículos , Poluentes Atmosféricos/análise , Carbono , China , Monitoramento Ambiental , Humanos , Fuligem/análise , Emissões de Veículos/análise
12.
Nat Prod Res ; 36(8): 2049-2055, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33185141

RESUMO

A new N-methoxy-1-pyridone alkaloid [chromenopyridin A (1)] and four known compounds (2-5) were isolated and identified from the endophytic fungus Penicillium nothofagi P-6, which was derived from the bark of the critically endangered conifer Abies beshanzuensis. Their structures were elucidated by extensive spectroscopic analyses and single-crystal X-ray diffraction. Among the isolates, compound 1 showed considerable cytotoxicities against the A549 and Hela human cancer cell lines, with IC50 values of 14.7 and 11.3 µM. In addition, compounds 1 and 4 exhibited potent antibacterial activity against Staphylococcus aureus with MIC values of 62.5 and 15.6 µg/mL, respectively.


Assuntos
Abies , Alcaloides , Penicillium , Traqueófitas , Alcaloides/química , Antibacterianos/química , Fungos/química , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Penicillium/química , Piridonas/farmacologia
13.
Nat Prod Res ; 35(19): 3248-3253, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31782673

RESUMO

Two new [asperxins A (1) and B (2)] and four known (3-6) aflatoxins were isolated and identified from the endophytic fungus Aspergillus sp. Y-2, which was derived from the needles of the critically endangered conifer Abies beshanzuensis. Their structures were elucidated by extensive spectroscopic methods. Among the isolates, compounds 1 and 5 showed considerable cytotoxicities against the A549 and Hela human cancer cell lines, with IC50 values in the range of 7.5-16.8 µM.


Assuntos
Abies , Aflatoxinas , Antineoplásicos/farmacologia , Aspergillus/química , Células A549 , Abies/microbiologia , Aflatoxinas/isolamento & purificação , Aflatoxinas/farmacologia , Antineoplásicos/isolamento & purificação , Espécies em Perigo de Extinção , Células HeLa , Humanos , Estrutura Molecular
14.
Bioorg Chem ; 105: 104445, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33197848

RESUMO

Rare and endangered plants (REPs) and their associated endophytes survived in unique habitats are promising sources for natural product-derived drug discovery. In this study, six new (cephaloverines A-F, 1-6, resp.) and 16 known (11-26) cephalotaxine-type alkaloids, together with three new (oliverbiflavones A-C, 7-9, resp.) and 11 known (27-37) biflavonoids were isolated and characterized from the twigs and leaves of Cephalotaxus oliveri, an endangered plant endemic to China. Meanwhile, a preliminary investigation on the secondary metabolites from a selected fungal endophyte (i.e., Alternaria alternate Y-4-2) associated with the title plant led to the isolation of 21 structurally distinct polyketides including one new dimeric xanthone (10). The new structures (1-10) with the absolute configurations were determined by detailed spectroscopic analyses, electronic circular dichroism (ECD) or Na2MoO4-induced ECD, the modified Mosher's method, and some chemical transformations. Compounds 1-4 are the first representatives of naturally occurring N-oxides of cephalotaxine esters, while compounds 7-9 have a special structural feature of having a C-methylated biflavonoid skeleton. The Cephalotaxus alkaloids with ester side-chains at C-3 (1-6, 13-22, and 26) and four biflavonoids (27-29 and 34) were found to show pronounced cytotoxicities against a small panel of human cancer cell lines (A549, NCI-H460, HL60, NCI-H929, and RPMI-8226), with IC50 values mainly ranging from 0.003 to 9.34 µM. The most potent compound, deoxyharringtonine (16), generally exhibited IC50 values less than 10 nM. The structure-activity relationship (SAR) of the aforementioned Cephalotaxus alkaloids was briefly discussed.


Assuntos
Alternaria/efeitos dos fármacos , Antineoplásicos/isolamento & purificação , Biflavonoides/isolamento & purificação , Cephalotaxus/química , Folhas de Planta/química , Antineoplásicos/farmacologia , Biflavonoides/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Endófitos , Mepesuccinato de Omacetaxina/química , Humanos , Estrutura Molecular , Policetídeos/química , Metabolismo Secundário , Relação Estrutura-Atividade , Xantonas/química
15.
J Nat Prod ; 83(7): 2129-2144, 2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32633512

RESUMO

A phytochemical investigation of the MeOH extract of the leaves and twigs of Amentotaxus argotaenia, a relict vulnerable coniferous species endemic to China, led to the isolation and characterization of 35 diterpenoids/norditerpenoids. Twenty of these are new, including 11 ent-kaurane-type (amentotaxins C-M, 1-11, respectively), three icetexane-type [= 9(10→20)abeo-abietane-type (amentotaxins N-P, 12-14, respectively)], four ent-labdane-type (amentotaxins Q-T, 15-18, respectively), and two isopimarane-type [amentotaxins U (19) and V (20)] compounds. Their structures were elucidated on the basis of spectroscopic data, single-crystal X-ray diffraction, the modified Mosher's method, and electronic circular dichroism data analyses. Compounds 1-9 are rare 18-nor-ent-kaurane-type diterpenoids featuring a 4ß,19-epoxy ring. All the isolates were evaluated for their cytotoxic effects against a small panel of cultured human cancer cell lines (HeLa, A-549, MDA-MB-231, SKOV3, Huh-7, and HCT-116), and some of them exhibited cytotoxicities with IC50 values ranging from 1.5 to 10.0 µM.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Folhas de Planta/química , Taxaceae/química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Análise Espectral/métodos
16.
Bioorg Med Chem ; 28(5): 115229, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32033878

RESUMO

Many human diseases, including cystic fibrosis lung infections, are caused or exacerbated by bacterial biofilms. Specialized modes of motility, including swarming and twitching, allow gram-negative bacteria to spread across surfaces and form biofilms. Compounds that inhibit these motilities could slow the spread of biofilms, thereby allowing antibiotics to work better. We previously demonstrated that a set of plant-derived triterpenes, including oleanolic acid and ursolic acid, inhibit formation of Escherichia coli and Pseudomonas aeruginosa biofilms, and alter expression of genes involved in chemotaxis and motility. In the present study, we have prepared a series of analogs of oleanolic acid. The analogs were evaluated against clinical isolates of E. coli and P. aeruginosa in biofilm formation assays and swarming assays. From these analogs, compound 9 was selected as a lead compound for further development. Compound 9 inhibits E. coli biofilm formation at 4 µg/mL; it also inhibits swarming at ≤1 µg/mL across multiple clinical isolates of P. aeruginosa, E. coli, Burkholderia cepacia, and Salmonella enterica, and at <0.5 µg/mL against multiple agricultural strains. Compound 9 also potentiates the activity of the antibiotics tobramycin and colistin against swarming P. aeruginosa; this is notable, as tobramycin and colistin are inhaled antibiotics commonly used to treat P. aeruginosa lung infections in people with cystic fibrosis. qPCR experiments suggested that 9 alters expression of genes involved in regulating Type IV pili; western blots confirmed that expression of Type IV pili components PilA and PilY1 decreases in P. aeruginosa in the presence of 9.


Assuntos
Aminas/farmacologia , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Aminas/síntese química , Aminas/química , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade
17.
J Am Chem Soc ; 142(4): 1673-1679, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31922407

RESUMO

We report the genome-guided discovery of sungeidines, a class of microbial secondary metabolites with unique structural features. Despite evolutionary relationships with dynemicin-type enediynes, the sungeidines are produced by a biosynthetic gene cluster (BGC) that exhibits distinct differences from known enediyne BGCs. Our studies suggest that the sungeidines are assembled from two octaketide chains that are processed differently than those of the dynemicin-type enediynes. The biosynthesis also involves a unique activating sulfotransferase that promotes a dehydration reaction. The loss of genes, including a putative epoxidase gene, is likely to be the main cause of the divergence of the sungeidine pathway from other canonical enediyne pathways. The findings disclose the surprising evolvability of enediyne pathways and set the stage for characterizing the intriguing enzymatic steps in sungeidine biosynthesis.


Assuntos
Vias Biossintéticas , Enedi-Inos/metabolismo , Antibióticos Antineoplásicos/metabolismo , Família Multigênica
18.
Phytochemistry ; 169: 112161, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31600653

RESUMO

A phytochemical investigation on the MeOH extract of the twigs and needles of the endangered plant Picea brachytyla led to the isolation and characterization of thirty-eight structurally diverse terpenoids. Seven of these molecules are previously undescribed, including three abietane-type (brachytylins A-C) and one labdane-type (brachytylin D) diterpenoids, an unseparated C-24 epimeric mixture of cycloartane-type triterpenoids (brachytylins E/F, ratio: 1:1), and a rare rearranged 12(1 → 6)-abeo-megastigmane glycoside (brachytylins G). Their structures and absolute configurations were determined by extensive spectroscopic (e.g., detailed 2D NMR and ECD) methods and/or X-ray diffraction analyses. All the isolates were evaluated for their inhibitory activities against the adenosine triphosphate (ATP)-citrate lyase (ACL) and the Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2). Among them, abiesadine J showed inhibitory effect against ACL, displaying an IC50 value of 17 µM. 3S,23R-Dihydroxycycloart-24-en-26-oic acid exhibited inhibitory effect on SHP2, with an IC50 value of 19 µM. Meanwhile, 3R*,23S*-dihydroxycycloart-24-en-26-oic acid was found to have inhibitory effects against both ACL and SHP2, with IC50 values of 16 and 12 µM, respectively.


Assuntos
ATP Citrato (pro-S)-Liase/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Compostos Fitoquímicos/farmacologia , Picea/química , Componentes Aéreos da Planta/química , Proteína Tirosina Fosfatase não Receptora Tipo 11/antagonistas & inibidores , Terpenos/farmacologia , ATP Citrato (pro-S)-Liase/metabolismo , China , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Humanos , Modelos Moleculares , Conformação Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Relação Estrutura-Atividade , Terpenos/química , Terpenos/isolamento & purificação
19.
J Coll Physicians Surg Pak ; 29(10): 946-950, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31564267

RESUMO

OBJECTIVE: To compare the efficacies of unilateral and bilateral percutaneous kyphoplasty (PKP) in the treatment of thoracolumbar osteoporotic compression fractures. STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Department of Orthopedics, Hubei 672 Orthopedics Hospital of Integrated Chinese and Western Medicine, China, from November 2014 to January 2017. METHODOLOGY: One hundred and seventy-eight patients with single-level thoracolumbar osteoporotic compression fractures included in this study. These patients were randomly assigned to unilateral (n=83) and bilateral (n=95) PKP groups. The operation time, bone cement volume, number of X-ray views, preoperative and postoperative pain visual analogue scale scores (VAS), Oswestry Dysfunction Index (ODI), Cobb angle, and vertebral height in both groups were recorded. RESULTS: Operation time, bone cement volume and intraoperative number of X-ray views were significantly different between unilateral and bilateral PKP groups (29.8 ±2.7 vs. 31.5 ±3.9 minutes; 9.3 ±2.6 vs. 11.2 ±3.7 times; 3.1 ±0.7 vs. 3.5 ±1.2 ml, respectively, p <0.05). VAS scores and ODI in both groups were significantly different before and 24 hours, 3 months and 6 months after surgery. The heights of anterior and middle borders of vertebral body and Cobb angle in the two groups were significantly different before and after surgery (p <0.05). CONCLUSION: The short-term efficacy was identical between unilateral and bilateral PKP. The unilateral PKP is characterized by short operation time, low hospital cost, less number of X-ray views and less bone cement volume. The unilateral PKP shows a higher risk of re-fracture of adjacent vertebral body compared with the bilateral PKP.


Assuntos
Cifoplastia/métodos , Fraturas por Osteoporose/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Idoso , Idoso de 80 Anos ou mais , Cimentos Ósseos , China , Avaliação da Deficiência , Feminino , Humanos , Vértebras Lombares/cirurgia , Masculino , Duração da Cirurgia , Fraturas por Osteoporose/diagnóstico por imagem , Medição da Dor , Fraturas da Coluna Vertebral/diagnóstico por imagem , Vértebras Torácicas/cirurgia
20.
Se Pu ; 37(2): 207-215, 2019 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-30693730

RESUMO

A gas chromatography-tandem mass spectrometry (GC-MS/MS) method was established for the determination of 10 volatile N-nitrosamines in meat products. The meat samples were extracted by simultaneous distillation extraction (SDE), and then a cleanup step involving the frozen fat removal method was applied. The analytes were quantified by the external standard method in multiple reaction monitoring (MRM) mode. Under the optimized conditions, the correlation coefficients of the standard calibration curves were greater than 0.99 in the range of 1.00-1000 µg/L. The limits of detection (LODs, S/N=3) and limits of quantification (LOQs, S/N=10) were 0.01-0.02 µg/kg and 0.04-0.07 µg/kg, respectively. The average spiked recoveries of the 10 volatile N-nitrosamines were 74.8%-94.3% at spiked levels of LOQ level, 1.0 and 2.0 µg/kg,and the relative standard deviations were less than 8.3%. Six volatile N-nitrosamines (N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosopyrrolidine (NPYR), N-nitrosopiperidine (NPIP), N-nitrosodibutylamine (NDBA) and N-nitrosodi-n-propylamine (NDPA)) were detected in different types of meat products, and each volatile N-nitrosamine in pickled meat products had the highest detection values. The developed method has the advantages of simplicity, sufficient extraction, high sensitivity, and low reagent dosage, in addition to proving suitable for the daily testing requirements of a large number of samples in the laboratory.


Assuntos
Produtos da Carne/análise , Nitrosaminas/análise , Dimetilnitrosamina , Cromatografia Gasosa-Espectrometria de Massas , Espectrometria de Massas em Tandem
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