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1.
Environ Sci Technol ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900493

RESUMO

Rubber-derived chemicals (RDCs) originating from tire and road wear particles are transported into road stormwater runoff, potentially threatening organisms in receiving watersheds. However, there is a lack of knowledge on time variation of novel RDCs in runoff, limiting initial rainwater treatment and subsequent rainwater resource utilization. In this study, we investigated the levels and time-concentration profiles of 35 target RDCs in road stormwater runoff from eight functional areas in the Greater Bay Area, South China. The results showed that the total concentrations of RDCs were the highest on the expressway compared with other seven functional areas. N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), 6PPD-quinone, benzothiazole, and 1,3-diphenylguanidine were the top four highlighted RDCs (ND-228840 ng/L). Seasonal and spatial differences revealed higher RDC concentrations in the dry season as well as in less-developed regions. A lag effect of reaching RDC peak concentrations in road stormwater runoff was revealed, with a lag time of 10-90 min on expressways. Small-intensity rainfall triggers greater contamination of rubber-derived chemicals in road stormwater runoff. Environmental risk assessment indicated that 35% of the RDCs posed a high risk, especially PPD-quinones (risk quotient up to 2663). Our findings contribute to a better understanding of managing road stormwater runoff for RDC pollution.

2.
Acta Pharmacol Sin ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862817

RESUMO

Suppression of neuroinflammation using small molecule compounds targeting the key pathways in microglial inflammation has attracted great interest. Recently, increasing attention has been gained to the role of the second bromodomain (BD2) of the bromodomain and extra-terminal (BET) proteins, while its effect and molecular mechanism on microglial inflammation has not yet been explored. In this study, we evaluated the therapeutic effects of ABBV-744, a BD2 high selective BET inhibitor, on lipopolysaccharide (LPS)-induced microglial inflammation in vitro and in vivo, and explored the key pathways by which ABBV-744 regulated microglia-mediated neuroinflammation. We found that pretreatment of ABBV-744 concentration-dependently inhibited the expression of LPS-induced inflammatory mediators/enzymes including NO, TNF-α, IL-1ß, IL-6, iNOS, and COX-2 in BV-2 microglial cells. These effects were validated in LPS-treated primary microglial cells. Furthermore, we observed that administration of ABBV-744 significantly alleviated LPS-induced activation of microglia and transcriptional levels of pro-inflammatory factors TNF-α and IL-1ß in mouse hippocampus and cortex. RNA-Sequencing (RNA-seq) analysis revealed that ABBV-744 induced 508 differentially expressed genes (DEGs) in LPS-stimulated BV-2 cells, and gene enrichment and gene expression network analysis verified its regulation on activated microglial genes and inflammatory pathways. We demonstrated that pretreatment of ABBV-744 significantly reduced the expression levels of basic leucine zipper ATF-like transcription factor 2 (BATF2) and interferon regulatory factor 4 (IRF4), and suppressed JAK-STAT signaling pathway in LPS-stimulated BV-2 cells and mice, suggesting that the anti-neuroinflammatory effect of ABBV-744 might be associated with regulation of BATF2-IRF4-STAT1/3/5 pathway, which was confirmed by gene knockdown experiments. This study demonstrates the effect of a BD2 high selective BET inhibitor, ABBV-744, against microglial inflammation, and reveals a BATF2-IRF4-STAT1/3/5 pathway in regulation of microglial inflammation, which might provide new clues for discovery of effective therapeutic strategy against neuroinflammation.

3.
Chem Biodivers ; 21(6): e202400519, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38576052

RESUMO

One new highly degraded steroid, namely 21-nor-4-ene-chaxine A (1) furnishing a 5/6/5-tricyclic, along with one known related analogue (2), were isolated from the South China Sea sponge Spongia officinalis. Their structures including absolute configurations were established by extensive spectroscopic data analysis, TDDFT-ECD calculation, and comparison with the spectral data previously reported in the literature. Compound 1 represent the new member of incisterols family with a highly degradation in ring B. In vitro bioassays revealed compound 2 exhibited significant anti-microglial inflammatory effect on lipopolysaccharide (LPS)-induced inflammation in BV-2 microglial cells.


Assuntos
Anti-Inflamatórios , Lipopolissacarídeos , Poríferos , Esteroides , Animais , Poríferos/química , Esteroides/química , Esteroides/isolamento & purificação , Esteroides/farmacologia , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , China , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/citologia , Linhagem Celular , Conformação Molecular , Estrutura Molecular
4.
Hepatobiliary Pancreat Dis Int ; 23(3): 272-287, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37407412

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) has a poor long-term prognosis. The competition of circular RNAs (circRNAs) with endogenous RNA is a novel tool for predicting HCC prognosis. Based on the alterations of circRNA regulatory networks, the analysis of gene modules related to HCC is feasible. METHODS: Multiple expression datasets and RNA element targeting prediction tools were used to construct a circRNA-microRNA-mRNA network in HCC. Gene function, pathway, and protein interaction analyses were performed for the differentially expressed genes (DEGs) in this regulatory network. In the protein-protein interaction network, hub genes were identified and subjected to regression analysis, producing an optimized four-gene signature for prognostic risk stratification in HCC patients. Anti-HCC drugs were excavated by assessing the DEGs between the low- and high-risk groups. A circRNA-microRNA-hub gene subnetwork was constructed, in which three hallmark genes, KIF4A, CCNA2, and PBK, were subjected to functional enrichment analysis. RESULTS: A four-gene signature (KIF4A, CCNA2, PBK, and ZWINT) that effectively estimated the overall survival and aided in prognostic risk assessment in the The Cancer Genome Atlas (TCGA) cohort and International Cancer Genome Consortium (ICGC) cohort was developed. CDK inhibitors, PI3K inhibitors, HDAC inhibitors, and EGFR inhibitors were predicted as four potential mechanisms of drug action (MOA) in high-risk HCC patients. Subsequent analysis has revealed that PBK, CCNA2, and KIF4A play a crucial role in regulating the tumor microenvironment by promoting immune cell invasion, regulating microsatellite instability (MSI), and exerting an impact on HCC progression. CONCLUSIONS: The present study highlights the role of the circRNA-related regulatory network, identifies a four-gene prognostic signature and biomarkers, and further identifies novel therapy for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , RNA Circular/genética , Prognóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , RNA Endógeno Competitivo , Fosfatidilinositol 3-Quinases , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , MicroRNAs/genética , Microambiente Tumoral , Cinesinas
5.
Mod Pathol ; 36(8): 100186, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37059230

RESUMO

Population-based cervical cytology screening techniques are demanding and laborious and have relatively poor diagnostic accuracy. In this study, we present a cytologist-in-the-loop artificial intelligence (CITL-AI) system to improve the accuracy and efficiency of abnormal cervical squamous cell detection in cervical cancer screening. The artificial intelligence (AI) system was developed using 8000 digitalized whole slide images, including 5713 negative and 2287 positive cases. External validation was performed using an independent, multicenter, real-world data set of 3514 women, who were screened for cervical cancer between 2021 and 2022. Each slide was assessed using the AI system, which generated risk scores. These scores were then used to optimize the triaging of true negative cases. The remaining slides were interpreted by cytologists who had varying degrees of experience and were categorized as either junior or senior specialists. Stand-alone AI had a sensitivity of 89.4% and a specificity of 66.4%. These data points were used to establish the lowest AI-based risk score (ie, 0.35) to optimize the triage configuration. A total of 1319 slides were triaged without missing any abnormal squamous cases. This also reduced the cytology workload by 37.5%. Reader analysis found CITL-AI had superior sensitivity and specificity compared with junior cytologists (81.6% vs 53.1% and 78.9% vs 66.2%, respectively; both with P < .001). For senior cytologists, CITL-AI specificity increased slightly from 89.9% to 91.5% (P = .029); however, sensitivity did not significantly increase (P = .450). Therefore, CITL-AI could reduce cytologists' workload by more than one-third while simultaneously improving diagnostic accuracy, especially compared with less experienced cytologists. This approach could improve the accuracy and efficiency of abnormal cervical squamous cell detection in cervical cancer screening programs worldwide.


Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Inteligência Artificial , Esfregaço Vaginal/métodos , Detecção Precoce de Câncer/métodos , Células Epiteliais/patologia
6.
Langmuir ; 39(18): 6399-6405, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37105949

RESUMO

Ex-service SF6 adsorbents in SF6 gas-insulated electric equipment contain many toxic substances. Inside, HF and H2S are two typical toxic gases. Based on the first principle, the interaction process between HF/H2S and α-Al2O3 (0001) surfaces was calculated using the density functional theory (DFT). The results showed that the adsorption of HF on α-Al2O3 (0001) is stronger than that of H2S. Under the five adsorption sites, the adsorption effect of HF-H and HF-F was similar. At O-2 site, the adsorption energy of H2S-H adsorption configuration is significantly higher than that of the other four sites. The density of states (DOS) indicated that new peaks appeared after adsorption. The DOS and partial density of states (PDOS) indicated that the adsorption of HF and H2S occurs via chemical adsorption. The DOS and PDOS shifted to the right when the S atom was approaching, proving that the system shifts to instability. Compared with the energy gap of α-Al2O3 (0001), HF and H2S adsorption systems decreased significantly. The energy gap of the HF adsorption system was 1.173 eV larger than that of the H2S system and the geometry was relatively stable, which is consistent with the DOS and PDOS adsorption calculation results. Thus, the adsorption of HF and H2S on α-Al2O3 (0001) surfaces was clearly different. The findings of this study may provide theoretical guidance for the adsorption of other gases or developing a new adsorbent.

7.
BMC Infect Dis ; 23(1): 584, 2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37674103

RESUMO

OBJECTIVE: To estimate the prevalence and risk factors associated with tuberculosis (TB) among people living with human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) in China. METHODS: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. After the literature was screened based on the inclusion and exclusion criteria, STATA® version 17.0 software was used for the meta-analysis. The heterogeneity among study data was assessed using I2 statistics. Subgroup analysis and meta-regressions were performed to further explore the source of heterogeneity. RESULTS: A total of 5241 studies were retrieved. Of these, 44 studies were found to be eligible. The pooled prevalence of HIV/TB co-infection was 6.0%. The risk factors for HIV/TB co-infection included a low CD4+ T cell count, smoking, intravenous drug use and several other sociodemographic and clinical factors. Bacillus Calmette-Guérin (BCG) vaccination history was a protective factor. CONCLUSION: A high prevalence of TB was observed among people living with HIV/AIDS in China. Low CD4+ T cell count, smoking, and intravenous drug use were the primary risk factors for HIV/TB co-infection, whereas BCG vaccination history was a protective factor. Checking for TB should be prioritized in HIV screening and healthcare access. SYSTEMATIC REVIEW REGISTRATION: Registered on PROSPERO, Identifier: CRD42022297754.


Assuntos
Síndrome da Imunodeficiência Adquirida , Coinfecção , Tuberculose , Humanos , Vacina BCG , Coinfecção/epidemiologia , Prevalência , Fatores de Risco , Tuberculose/epidemiologia , China/epidemiologia
8.
J Nat Prod ; 86(10): 2315-2325, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37728995

RESUMO

Eleven densely functionalized new dihydro-ß-agarofuran sesquiterpenoid derivatives, named maytenoids A-K (1-11), as well as one known analog, were isolated and characterized from Maytenus austroyunnanensis. Their structures were assigned based on analysis of spectroscopic data and X-ray crystallography. Compounds 1-9 are macrocyclic sesquiterpene pyridine alkaloids generated by the respective acylation of the hydroxy groups at C-3 and C-13 of dihydro-ß-agarofuran sesquiterpenoids via diverse pyridine dicarboxylic acids. Compounds 1, 2, 5-10, and 12 exhibited significant inhibitory effects on NO production at 10 µM in lipopolysaccharide (LPS)-stimulated BV2 cells.


Assuntos
Alcaloides , Maytenus , Sesquiterpenos , Maytenus/química , Estrutura Molecular , Alcaloides/farmacologia , Alcaloides/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Piridinas/química
9.
Ecotoxicol Environ Saf ; 264: 115419, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37651793

RESUMO

Cadmium (Cd) is one of the toxic heavy metal that negatively affect plant growth and compromise food safety for human consumption. Nitrogen (N) is an essential macronutrient for plant growth and development. It may enhance Cd tolerance of invasive plant species by maintaining biochemical and physiological characteristics during phytoextraction of Cd. A comparative study was conducted to evaluate the phenotypical and physiological responses of invasive W. trilobata and native W. chinensis under low Cd (10 µM) and high Cd (80 µM) stress, along with different N levels (i.e., normal 91.05 mg kg-1 and low 0.9105 mg kg-1). Under low-N and Cd stress, the growth of leaves, stem and roots in W. trilobata was significantly increased by 35-23%, 25-28%, and 35-35%, respectively, compared to W. chinensis. Wedelia trilobata exhibited heightened antioxidant activities of catalase and peroxidase were significantly increased under Cd stress to alleviate oxidative stress. Similarly, flavonoid content was significantly increased by 40-50% in W. trilobata to promote Cd tolerance via activation of the secondary metabolites. An adverse effect of Cd in the leaves of W. chinensis was further verified by a novel hyperspectral imaging technology in the form of normalized differential vegetation index (NDVI) and photochemical reflectance index (PRI) compared to W. trilobata. Additionally, W. trilobata increased the Cd tolerance by regulating Cd accumulation in the shoots and roots, bolstering its potential for phytoextraction potential. This study demonstrated that W. trilobata positively responds to Cd with enhanced growth and antioxidant capabilities, providing a new platform for phytoremediation in agricultural lands to protect the environment from heavy metals pollution.


Assuntos
Asteraceae , Wedelia , Humanos , Cádmio/toxicidade , Solo , Nitrogênio , Antioxidantes , Metais
10.
Chem Biodivers ; 20(8): e202300821, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37376927

RESUMO

Three new steroids, along with two known related analogs, were isolated from the Xisha Island soft coral Lobophytum sarcophytoides. The structures and absolute configurations of the new compounds were elucidated by extensive spectroscopic data analyses, time dependent density functional theory electronic circular dichroism calculation, and comparison with the spectral data previously reported in the literature. In in vitro bioassay, four compounds showed interesting suppressive effects on lipopolysaccharide (LPS) induced inflammation in BV-2 microglial cells at 10 µM level.


Assuntos
Antozoários , Diterpenos , Animais , Antozoários/química , Esteroides/farmacologia , Esteroides/química , Anti-Inflamatórios/farmacologia , China , Lipopolissacarídeos/farmacologia , Diterpenos/química , Estrutura Molecular
11.
Int J Mol Sci ; 24(24)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38139253

RESUMO

Ammonium, as a major inorganic source of nitrogen (N) for sweet potato N utilization and growth, is specifically transported by ammonium transporters (AMTs). However, the activities of AMT family members in sweet potatoes have not been analyzed. In the present study, the sweet potato cultivar 'Pushu 32', which is planted in a large area in China, was used in field experiments at the Agricultural Base of Hainan University (20°06' N, 110°33' E) in 2021, and Sanya Nanfan Research Institute of Hainan University (18°30' N, 109°60' E) in 2022. Four N levels were tested: 0, 60, 120, and 180 kg ha-1. The results are as follows. Twelve IbAMT genes were identified in the sweet potato genome, which were classified into three distinct subgroups based on phylogeny; the same subgroup genes had similar properties and structures. IbAMT1.3 and IbAMT1.5 were mostly expressed in the storage roots under N deficiency. Compared with the NN and HN groups, IbAMT1.3 and IbAMT1.5 expressions, N content in storage roots, N uptake efficiency at the canopy closure, N fertilization contribution rates, number of storage roots per plant, storage root weight, and yield were all increased in the MN group. Furthermore, there was a significant positive correlation between the expressions of IbAMT1.3 and IbAMT1.5 with N content in the storage roots of sweet potato. In a word, IbAMT1.3 and IbAMT1.5 may regulate N utilization, affect the development of the storage root. and determine the yield of sweet potato. The results provide valuable insights into the AMT gene family's role in the use of N and effects on storage root development and yield in sweet potatoes.


Assuntos
Ipomoea batatas , Humanos , Ipomoea batatas/metabolismo , Agricultura , Nitrogênio/metabolismo , China , Raízes de Plantas/metabolismo
12.
J Cell Mol Med ; 26(11): 3133-3146, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35582765

RESUMO

This study sought to determine whether mesenchymal stem cells-derived extracellular vesicles (MSCs-EVs) carrying microRNA-378a-3p (miR-378a-3p) could affect the pathogenesis of inflammatory bowel disease (IBD) by regulating the GATA-binding protein 2 (GATA2)/aquaporin-4 (AQP4)/peroxisome proliferator-activated receptor α (PPAR-α) axis. Initially, colon mucosa biopsy tissues were harvested from healthy controls and patients with IBD for qRT-PCR and immunohistochemistry analysis. EVs harvested from MSCs and lipopolysaccharide (LPS) were used to stimulate the M064 cells to establish an in vitro inflammation cell model. Besides, 2,4,6-trinitrobenzene sulfonic acid intracolon administration was performed to establish in vivo IBD mouse models. After loss- and gain-of-function assays, the regulatory role of MSCs-derived EVs loaded with manipulated miR-378a-3p in IBD in relation to GATA2/AQP4/PPAR-α were explored. Upregulation of GATA2 was identified in the colon tissue of IBD patients. GATA2, which was a target gene of miR-378a-3p, transcriptionally upregulated AQP4. After silencing of GATA2, LPS-induced apoptosis of M064 cells was reduced by the downregulation of AQP4. Decreased AQP4 contributed to PPAR-α pathway inactivation and weakened the LPS-induced apoptosis of M064 cells. MSCs-EVs delivering miR-378a-3p suppressed the GATA2/AQP4/PPAR-α pathway, which reduced LPS-induced apoptosis of M064 cells and the occurrence of IBD in mice. Altogether, the current study illustrated that MSCs-EVs transfer miR-378a-3p to reduce the GATA2 expression, which downregulates AQP4 to block the PPAR-α signalling pathway, thus suppressing the occurrence of IBD.


Assuntos
Vesículas Extracelulares , Doenças Inflamatórias Intestinais , Células-Tronco Mesenquimais , MicroRNAs , Animais , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Fator de Transcrição GATA2/genética , Fator de Transcrição GATA2/metabolismo , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/metabolismo , Lipopolissacarídeos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo
13.
Neoplasma ; 69(3): 550-559, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35188403

RESUMO

Laryngeal squamous cell carcinoma (LSCC) is the most common malignant tumor in the head and neck cancer, with a poor prognosis. As we know, microRNAs (miRNAs) play a vital role in the initiation and development of various cancers including LSCC. In this study, we explored the role of miR-125b-5p and its downstream regulatory pathway in LSCC. Our data demonstrated that miR-125b-5p expression was significantly downregulated in LSCC tissues and cells. LSCC patients with high expression of miR-125b-5p had higher overall survival (OS) and were closely related to the clinical stage. Overexpression of miR-125b-5p impaired viability and glycolysis, and facilitated apoptosis in LSCC cells. And miR-125b-5p silencing had the opposite effects. Bioinformatics website predicted that MAP3K9 was one of the potential target genes of miR-125b-5p. Cell experiments demonstrated that miR-125b-5p repressed the MAP3K9 levels by directly targeting MAP3K9. Additionally, the negative correlation between miR-125b-5p and MAP3K9 was validated in LSCC tissues. Overexpression of MAP3K9 attenuated the inhibitory effect of miR-125b-5p on viability and glycolysis, and the pro-apoptosis effect of miR-125b-5p in LSCC cells. Furthermore, in vivo experiments demonstrated that tumor growth was hampered in AMC-HN-8 cells transfected with miR-125b-5p mimic. In contrast, the knockdown of miR-125b-5p reduced tumor growth in vivo. Meanwhile, the in vivo immunohistochemistry and TUNEL assays suggested that the miR-125b-5p overexpression restrained cell proliferation and promoted apoptosis via targeting MAP3K9. Overall, these above results suggested that miR-125b-5p suppressed proliferation and glycolysis, and promoted apoptosis by directly targeting MAP3K9 in LSCC cells. Thus, miR-125b-5p acts as a tumor suppressor miRNA and the miR-125b-5p/MAP3K9 axis may be a promising candidate for LSCC treatment.


Assuntos
Neoplasias Laríngeas , MAP Quinase Quinase Quinases , MicroRNAs , Carcinoma de Células Escamosas de Cabeça e Pescoço , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , Neoplasias Laríngeas/patologia , MAP Quinase Quinase Quinases/genética , MAP Quinase Quinase Quinases/metabolismo , MicroRNAs/biossíntese , MicroRNAs/genética , MicroRNAs/metabolismo , Prognóstico
14.
Mar Drugs ; 20(10)2022 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-36286428

RESUMO

The first investigation of the South China Sea soft coral Sarcophyton boettgeri afforded five new capnosane diterpenes, sarboettgerins A-E (1-5), together with one known related compound, pavidolide D (6). Their structures, including absolute configurations, were elucidated by the extensive spectroscopic analysis, 13C NMR calculations, and X-ray diffraction. Among them, new compounds 1-5 were featured by the rarely encountered Z-geometry double bond Δ1 within the 5/11-fused bicyclic capnosane carbon framework. Plausible biogenetic relationships of all isolates were proposed, and they might give an insight into future biomimetic synthesis of these novel compounds. In an in vitro bioassay, compound 5 displayed potent anti-neuroinflammatory activity against LPS-induced NO release in BV-2 microglial cells, which might be developed as a new type of potential neuroprotective agent in future.


Assuntos
Antozoários , Diterpenos , Fármacos Neuroprotetores , Animais , Antozoários/química , Fármacos Neuroprotetores/farmacologia , Lipopolissacarídeos , Diterpenos/farmacologia , Diterpenos/química , China , Carbono , Estrutura Molecular
15.
J Asian Nat Prod Res ; 24(4): 336-343, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34092159

RESUMO

Three new sesquiterpene polyol ester compounds angulatins S-U, together with three known compounds were isolated from Celastrus angulatus Maxim. According to mainly 1D NMR and 2D NMR analysis, the structures of the new compounds were completely determined as angulatin S (1ß-furoyloxy-2ß,8α-diisobutanoyloxy-9ß-benzoyloxy-15-acetoxy-4α,6α-dihydroxy-ß-dihydroagarofuran), angulatin T (1ß,2ß,6α-triacetoxy-8ß,15-diisobutanoyloxy-9α-benzoyloxy-ß-dihydroagrofuran), and angulatin U (1ß,6α,15-triacetoxy-8ß-isobutanoyloxy-9α-benzoyloxy-ß-dihydroagarofuran).


Assuntos
Celastrus , Sesquiterpenos , Celastrus/química , Ésteres/química , Estrutura Molecular , Polímeros , Sesquiterpenos/química
16.
Rheumatology (Oxford) ; 60(3): 1054-1066, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33450018

RESUMO

BACKGROUND: Recently, researchers have proposed a possible relationship between RA and the microbiome of the oral cavity and gut. However, this relation has not been systematically established. Herein, we conducted a comprehensive review of the pertinent literature to describe this possible association. METHODS: We systematically performed searches in databases, namely EMBASE, the Cochrane Library, and PubMed, from inception to 7 June 2020 to identify case-control studies that compared the oral and gut microbiome in adult RA patients with those of controls. The primary outcome was specific bacterial changes between RA and controls. The secondary outcome was microbial diversity changes between RA and controls. RESULTS: In total, 26 articles were considered eligible for inclusion and reported some differences. Therein, ≥3 articles reported decreased Faecalibacterium in the gut of early-RA (ERA)/RA patients compared with healthy controls (HCs). Also, ≥3 articles reported decreased Streptococcus and Haemophilus and increased Prevotella in the oral cavity of ERA/RA patients compared with HCs. In addition, some Prevotella species, including P. histicola and P. oulorum, showed increased trends in RA patients' oral cavity, compared with HCs. The α-diversity of the microbiome was either increased or not changed in the oral cavity of RA patients, but it was more commonly either decreased or not changed in the gut of RA patients. CONCLUSIONS: In this systematic review, we identified the microbiome associated with RA patients in comparison with controls. More research is needed in the future to find the deep relationship between RA and the microbiome.


Assuntos
Artrite Reumatoide/microbiologia , Microbioma Gastrointestinal , Boca/microbiologia , Humanos
17.
Neurochem Res ; 46(3): 686-698, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33389470

RESUMO

28-O-caffeoyl betulin (B-CA) has been demonstrated to reduce the cerebral infarct volume caused by transient middle cerebral artery occlusion (MCAO) injury. B-CA is a novel derivative of naturally occurring caffeoyl triterpene with little information associated with its pharmacological target(s). To date no data is available regarding the effect of B-CA on brain metabolism. In the present study, a 1H-NMR-based metabolomics approach was applied to investigate the therapeutic effects of B-CA on brain metabolism following MCAO in rats. Global metabolic profiles of the cortex in acute period (9 h after focal ischemia onset) after MCAO were compared between the groups (sham; MCAO + vehicle; MCAO + B-CA). MCAO induced several changes in the ipsilateral cortex of ischemic rats, which consequently led to the neuronal damage featured with the downregulation of NAA, including energy metabolism dysfunctions, oxidative stress, and neurotransmitter metabolism. Treatment with B-CA showed statistically significant rescue effects on the ischemic cortex of MCAO rats. Specifically, treatment with B-CA ameliorated the energy metabolism dysfunctions (back-regulating the levels of succinate, lactate, BCAAs, and carnitine), oxidative stress (upregulating the level of glutathione), and neurotransmitter metabolism disturbances (back-regulating the levels of γ-aminobutyric acid and acetylcholine) associated with the progression of ischemic stroke. With the administration of B-CA, the levels of three phospholipid related metabolites (O-phosphocholine, O-phosphoethanolamine, sn-glycero-3-phosphocholine) and NAA improved significantly. Overall, our findings suggest that treatment with B-CA may provide neuroprotection by augmenting the metabolic changes observed in the cortex following MCAO in rats.


Assuntos
Córtex Cerebral/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Doenças Metabólicas/metabolismo , Metaboloma/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Triterpenos/uso terapêutico , Animais , Córtex Cerebral/efeitos dos fármacos , Infarto da Artéria Cerebral Média/tratamento farmacológico , Masculino , Doenças Metabólicas/tratamento farmacológico , Metabolômica , Espectroscopia de Prótons por Ressonância Magnética , Curva ROC , Ratos Sprague-Dawley
18.
J Org Chem ; 86(4): 3367-3376, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33497233

RESUMO

The chemical investigation of the South China Sea soft coral Sinularia humilis has resulted in the isolation of a library of diverse diterpenoids, including four new cembranoids, namely, humilisins A-D (1-4), two new uncommon diterpenoids possessing a tetradecahydrocyclopenta[3',4']cyclobuta[1',2':4,5]cyclonona[1,2-b]oxirene ring system, namely, humilisins E and F (5 and 6), and eight known related compounds (7-14). Humilisin A (1) is the first cembranoid with an ether linkage between C-3 and C-7. The structures and absolute configurations of 1-8 were determined by extensive spectroscopic data analyses, chemical reactions, and a series of quantum chemical calculations including quantum mechanical-nuclear magnetic resonance (QM-NMR), time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD), and optical rotatory dispersion (ORD) methods. In bioassay, compound 6 displayed anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated BV-2 microglia cells.


Assuntos
Antozoários , Diterpenos , Animais , China , Diterpenos/farmacologia , Lipopolissacarídeos/farmacologia , Estrutura Molecular
19.
J Org Chem ; 86(16): 11277-11283, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-33855855

RESUMO

Two eudesmane-guaiane/lindenane heterocoupled sesquiterpenoid dimers, horienoids A (1) and B (2) with new carbon skeletons, from Hedyosmum orientale were characterized by a combined method. Compound 1 featured a unique 2,10-dioxabicyclo[6.2.1]undecane core moiety with an anti-Bredt bridgehead double bond. Their biogenetic pathways were proposed to involve Diels-Alder and cascade rearrangement reactions as the key steps. Compound 2 exhibited a potent anti-inflammatory effect on LPS-induced BV-2 microglial cells.


Assuntos
Sesquiterpenos , Sesquiterpenos/farmacologia
20.
Bioorg Med Chem ; 38: 116139, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33857736

RESUMO

Six new cembrane-type diterpenoids, namely ximaoglaucumins A-F (1-6), along with fifteen known related ones (7-10 and 14-24), have been isolated from the soft coral Sarcophyton glaucum collected off the Ximao Island in the South China Sea. Their structures, including absolute stereochemistry, were elucidated by extensive spectroscopic analysis, quantum mechanical nuclear magnetic resonance (QM-NMR) methods, X-ray diffraction analysis, chemical methods, as well as comparison with the reported data in the literature. Further, detailed analysis of spectroscopic data of 7 not only clarified the confusions regarding 7, 11 (sarcophytolol) and 12/13 (sarcotrocheliol) in the literature, but also led to revise the structure of 11, which was mis-assigned due to careless/erroneous interpretation of the 2D NMR spectra, and to correct the structures of 12/13, which were both wrongly depicted. In in vitro bioassay, compounds 8 and 20 exhibited potent inhibitory effects on lipopolysaccharide (LPS)-induced inflammatory responses in BV-2 microglial cells.


Assuntos
Antozoários/química , Anti-Inflamatórios não Esteroides/farmacologia , Inflamação/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Linhagem Celular , China , Relação Dose-Resposta a Droga , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade
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