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1.
Environ Res ; 263(Pt 2): 120094, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39362459

RESUMEN

2,2',4,4'-tetra brominated diphenyl ether (BDE-47) is one of the most widely distributed congeners of polybrominated diphenyl ethers. While the relationships between BDE-47 exposure and other hormone-dependent cancers (such as breast cancer) are well established, no previous study has examined whether BDE-47 exposure is related to the development of prostate cancer (PCa). Through bulk and single-cell RNA sequencing (scRNA-seq) analyses, as well as in vitro and in vivo experiments, this study aims to investigate the effect of BDE-47 exposure on PCa progression. Herein, we found that low dose BDE-47 promoted the growth of PCa cells (PC3 and LNCaP) in a dose-dependent manner in vitro and in vivo. Based on Comparative Toxicogenomics Database (CTD) and The Cancer Genome Atlas (TCGA), we obtained 34 BDE-47-related and PCa-related genes through screening and overlapping. These genes were significantly enriched in fatty acid metabolism-related gene ontology (GO) terms, which were also enriched for genes targeting BDE-47 obtained from the UniProt. Through scRNA-seq data, certain cell type-specific expression was observed for CYP2E1, PIK3R1, FGF2, and TOP2A in PCa tissues from men. Molecular docking simulation showed that BDE-47 was tightly bound to the protein residues of AOX1, PIK3R1, FGF2, CAV2, CYP2E1 and TOP2A. Further screening in terms of patient overall survival, receiver operating characteristics curve (ROC) curve and Gleason score grading system narrowed the candidate genes down to TOP2A. Mechanistically, the growth-promoting effect of BDE-47 on PCa cells could be reversed by TOP2A inhibitor. RNA-seq followed by experimental verification demonstrated that TOP2A promoted PCa progression through upregulating LDHA and glycolysis. Furthermore, lactate upregulated TOP2A transcription through lactylation of H3K18la in PCa cells, which could be rescued by LDHA knockdown. Taken together, low dose BDE-47 triggered PCa progression through TOP2A/LDHA/lactylation positive feedback circuit, thus revealing epigenetic shifting and metabolic reprogramming underpinning BDE-47-induced carcinogenesis of the prostate.

2.
Front Cell Infect Microbiol ; 14: 1428827, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39318475

RESUMEN

The indiscriminate use of antibiotics has resulted in a growing resistance to drugs in Pseudomonas aeruginosa. The identification of antibiotic resistance genes holds considerable clinical significance for prompt diagnosis. In this study, we established and optimized a Recombinase-Aided Amplification (RAA) assay to detect two genes associated with drug resistance, oprD and arr, in 101 clinically collected P. aeruginosa isolates. Through screening for the detection or absence of oprD and arr, the results showed that there were 52 Imipenem-resistant P. aeruginosa (IRPA) strains and 23 Rifampin-resistant P. aeruginosa (RRPA) strains. This method demonstrated excellent detection performance even when the sample concentration is 10 copies/µL at isothermal conditions and the results could be obtained within 20 minutes. The detection results were in accordance with the results of conventional PCR and Real-time PCR. The detection outcomes of the arr gene were consistently with the resistance spectrum. However, the antimicrobial susceptibility results revealed that 65 strains were resistant to imipenem, while 49 strains sensitive to imipenem with oprD were identified. This discrepancy could be attributed to genetic mutations. In summary, the RAA has higher sensitivity, shorter time, and lower-cost instrument requirements than traditional detection methods. In addition, to analyze the epidemiological characteristics of the aforementioned drug-resistant strains, we conducted Multilocus Sequence Typing (MLST), virulence gene, and antimicrobial susceptibility testing. MLST analysis showed a strong correlation between the sequence types ST-1639, ST-639, ST-184 and IRPA, while ST-261 was the main subtype of RRPA. It was observed that these drug-resistant strains all possess five or more virulence genes, among which exoS and exoU do not coexist, and they are all multidrug-resistant strains. The non-coexistence of exoU and exoS in P.aeruginosa is related to various factors including bacterial regulatory mechanisms and pathogenic mechanisms. This indicates that the relationship between the presence of virulence genes and the severity of patient infection is worthy of attention. In conclusion, we have developed a rapid and efficient RAA (Recombinase-Aided Amplification) detection method that offers significant advantages in terms of speed, simplicity, and cost-effectiveness (especially in time and equipment aspect). This novel approach is designed to meet the demands of clinical diagnostics.


Asunto(s)
Antibacterianos , Imipenem , Pruebas de Sensibilidad Microbiana , Técnicas de Amplificación de Ácido Nucleico , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Recombinasas , Rifampin , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/aislamiento & purificación , Imipenem/farmacología , Rifampin/farmacología , Humanos , Antibacterianos/farmacología , Recombinasas/genética , Técnicas de Amplificación de Ácido Nucleico/métodos , Infecciones por Pseudomonas/microbiología , Farmacorresistencia Bacteriana/genética , Porinas/genética , Sensibilidad y Especificidad , Proteínas Bacterianas/genética , Técnicas de Diagnóstico Molecular/métodos
3.
Ecotoxicol Environ Saf ; 283: 116853, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39137468

RESUMEN

The effect and underlying mechanism of tetrabromobisphenol A (TBBPA), a plastic additive, on biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA USA300) remain unknown. This study first investigated the impact of different concentrations of TBBPA on the growth and biofilm formation of USA300. The results indicated that a low concentration (0.5 mg/L) of TBBPA promoted the growth and biofilm formation of USA300, whereas high concentrations (5 mg/L and 10 mg/L) of TBBPA had inhibitory effects. Further exploration revealed that the low concentration of TBBPA enhance biofilm formation by promoting the synthesis of extracellular proteins, release of extracellular DNA (eDNA), and production of staphyloxanthin. RTqPCR analysis demonstrated that the low concentration of TBBPA upregulated genes associated with extracellular protein synthesis (sarA, fnbA, fnbB, aur) and eDNA formation (atlA) and increased the expression of genes involved in staphyloxanthin biosynthesis (crtM), suggesting a potential mechanism for enhanced resistance of USA300 to adverse conditions. These findings shed light on how low concentrations of TBBPA facilitate biofilm formation in USA300 and highlight the indirect impact of plastic additives on pathogenic bacteria in terms of human health. In the future, in-depth studies about effects of plastic additives on pathogenicity of pathogenic bacteria should be conducted. CAPSULE: The protein and eDNA contents in biofilms of methicillin-resistant Staphylococcus aureus are increased by low concentrations of TBBPA.


Asunto(s)
Biopelículas , Staphylococcus aureus Resistente a Meticilina , Bifenilos Polibrominados , Biopelículas/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/fisiología , Bifenilos Polibrominados/toxicidad , Xantófilas , Proteínas Bacterianas/genética
4.
J Agric Food Chem ; 72(32): 17938-17952, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39092914

RESUMEN

Fifteen stilbenoid derivatives, including five previously undescribed ones (albaphenols A-E, 1-5) with diverse scaffolds, were obtained from the well-known agricultural economic tree Morus alba. Their structures, including absolute stereochemistries, were fully characterized by detailed interpretation of spectroscopic data and quantum chemical computational analyses of nuclear magnetic resonance (NMR) and electric circular dichroism (ECD). Albaphenol A (1) features an unprecedented rearranged carbon skeleton incorporating a novel 2-oxaspiro[bicyclo[3.2.1]octane-6,3'-furan] motif; albaphenol C (3) is likely derived from a cometabolite through an interesting intramolecular transesterification reaction; and albaphenol E (5) bears a cleavage-reconnection scaffold via a dioxane ring. All of the compounds exhibited significant inhibition against the diabetic target α-glucosidase, with low to submicromole IC50 values (0.70-8.27 µM), and the binding modes of selected molecules with the enzyme were further investigated by fluorescence quenching, kinetics, and molecular docking experiments. The antidiabetic effect of the most active and abundant mulberrofuran G (6) was further assessed in vivo in diabetic mice, revealing potent antihyperglycemic activity and comparable antidiabetic efficacy to the clinical drug acarbose.


Asunto(s)
Inhibidores de Glicósido Hidrolasas , Hipoglucemiantes , Simulación del Acoplamiento Molecular , Morus , Extractos Vegetales , Estilbenos , alfa-Glucosidasas , Animales , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/farmacología , Ratones , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Estilbenos/química , Estilbenos/farmacología , alfa-Glucosidasas/química , alfa-Glucosidasas/metabolismo , Masculino , Morus/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Humanos , Estructura Molecular , Relación Estructura-Actividad , Cinética
5.
Chem Biodivers ; : e202401646, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39102223

RESUMEN

A focused chemical investigation into the polar fractions of a well-known traditional Chinese medicine called Sang-Bai-Pi (the root bark of Morus alba) yielded a panel of prenylated flavanones. The new compounds were identified as four pairs of enantiomers (1a/1b-4a/4b) featuring the same constitution structure, on the basis of HRMS, NMR and ECD analyses. Several previously reported known racemic co-metabolites were also analyzed and separated by HPLC on chiral columns, and the absolute configurations of pure enantiomers were established via ECD technique for the first time. The inhibition of these isolates against the antidiabetic target α-glycosidase was further tested, with most of them showing decent inhibitory activity compared with the positive control acarbose. The interaction mechanism of two selected compounds (3a & 4b) was explored by kinetics experiment, which revealed a mixed type of inhibition pattern toward the enzyme.

6.
Mol Nutr Food Res ; 68(8): e2300745, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38581304

RESUMEN

SCOPE: Naringenin (NAR) possesses unique anti-inflammatory, antiapoptosis effects and various bioactivities; however, its role against radiation-induced intestinal injury (RIII) remains unclear. This study aims to investigate whether NAR has protective effects against radiation-induced intestinal injury and the underlying mechanisms. METHODS AND RESULTS: C57BL/6J mice are exposed to a single dose of 13 Gy X-ray total abdominal irradiation (TAI), then gavaged with NAR for 7 days. NAR treatment prolongs the survival rate, protects crypts and villi from damage, alleviates the level of radiation-induced inflammation, and mitigates intestinal barrier damage in the irradiated mice. Additionally, NAR reduces immune cell infiltration and intestinal epithelial cell apoptosis. NAR also shows radioprotective effects in human colon cancer cells (HCT116) and human intestinal epithelial cells (NCM460). It reduces cell damage by reducing intracellular calcium ion levels and reactive oxygen species (ROS) levels. NAR-mediated radioprotection is associated with the downregulation of transient receptor potential vanilloid 6 (TRPV6), and inhibition of apoptosis pathway. Notably, treatment with NAR fails to further increase the protective effects of the TRPV6 inhibitor 2-APB, indicating that TRPV6 inhibition is essential for NAR activity. CONCLUSION: NAR inhibits the apoptosis pathway by downregulating TRPV6 and reducing calcium ion level, thereby alleviating RIII. Therefore, NAR is a promising therapeutic drug for RIII.


Asunto(s)
Apoptosis , Flavanonas , Ratones Endogámicos C57BL , Especies Reactivas de Oxígeno , Canales Catiónicos TRPV , Animales , Flavanonas/farmacología , Humanos , Canales Catiónicos TRPV/metabolismo , Apoptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Masculino , Ratones , Protectores contra Radiación/farmacología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/efectos de la radiación , Mucosa Intestinal/metabolismo , Células HCT116 , Canales de Calcio/metabolismo , Intestinos/efectos de los fármacos , Intestinos/efectos de la radiación , Calcio/metabolismo , Traumatismos por Radiación/tratamiento farmacológico
7.
Biochem Genet ; 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38374521

RESUMEN

Klinefelter syndrome (KS) is the most frequent genetic anomaly in infertile men. Given its unclear mechanism, we aim to investigate critical genes and pathways in the pathogenesis of KS based on three bulk and one single-cell transcriptome data sets from Gene Expression Omnibus. We merged two data sets (GSE42331 and GSE47584) with human KS whole blood samples. When comparing the control and KS samples, five hub genes, including defensin alpha 4 (DEFA4), bactericidal permeability increasing protein (BPI), myeloperoxidase (MPO), intelectin 1 (ITLN1), and Xg Glycoprotein (XG), were identified. Besides, infiltrated degree of certain immune cells such as CD56bright NK cell were positively associated with the expression of ITLN1 and XG. Kyoto Encyclopedia of Genes and Genomes analysis identified upregulated phosphatidylinositol 3-kinase (PI3K)/AKT pathway in KS. Gene set enrichment analysis followed by gene set variation analysis confirmed the upregulation of G2M checkpoint and heme metabolism in KS. Thereafter, the GSE200680 data set was used for external validation of the expression variation of hub genes from healthy to KS testicular samples, and each hub gene yielded excellent discriminatory capability for KS without exception. At the single-cell level, the GSE136353 data set was utilized to evaluate intercellular communication between different cell types in KS patient, and strong correlations were detected between macrophages/ dendritic cells/ NK cells and the other cell types. Collectively, we provided hub genes, pathways, immune cell infiltration degree, and cell-cell communication in KS, warranting novel insights into the pathogenesis of this disease.

8.
Biomed Opt Express ; 15(1): 306-318, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38223167

RESUMEN

Plasmonic nanostructures have great potential for improving the radiation properties of emitters. Here, the plasmonic Au nanorods-PVA nanocomposite films are used to uniformly improve the photoluminescence of Tb/Eu co-doped PMMA film within the local micro-region. Under the excitation of 292 nm, the maximum enhancement factor is 37.2-fold for emission at 612 nm and 21.6-fold for emission at 545 nm. Moreover, the finite different time domain simulations are developed to further explain the experimental results. It is indicated that the modulation of luminescence can be attributed to the increase of the local density of optical states through the Purcell effect and the improvement of the energy transfer efficiency between Tb and Eu. Under the excitation of 360 nm, the maximum enhancement factor is about 71.5-fold. In this case, the Au nanorods are mainly used for modulating the emission process at 612 nm, which deduced a greater enhancement factor at 612 nm. This study provides a deep understanding of the interactions between rare earth ions co-doped materials and plasmonic nanostructures, building a bridge to fabricate a useful platform for several applications, such as thin film-based detectors and sensors.

9.
Disaster Med Public Health Prep ; 18: e12, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38287687

RESUMEN

INTRODUCTION: Nightclubs are entertainment and hospitality venues historically vulnerable to terrorist attacks. This study identified and characterized terrorist attacks targeting nightclubs and discotheques documented in the Global Terrorism Database (GTD) over a 50-y period. METHODS: A search of the Global Terrorism Database (GTD) was conducted from 1970 to 2019. Precoded variables for target type "business" and target subtype "entertainment/cultural/stadium/casino" were used to identify attacks potentially involving nightclubs. Nightclub venues were specifically identified using the search terms "club," "nightclub," and "discotheque." Two authors manually reviewed each entry to confirm the appropriateness for inclusion. Descriptive statistics were performed using R (3.6.1). RESULTS: A total of 114 terrorist attacks targeting nightclub venues were identified from January 1, 1970, through December 31, 2019. Seventy-four (64.9%) attacks involved nightclubs, while forty (35.1%) attacks involved discotheques. A bombing or explosion was involved in 84 (73.7%) attacks, followed by armed assault in 14 (12.3%) attacks. The highest number of attacks occurred in Western Europe and Sub-Saharan Africa. In total, 284 persons died, and 1175 persons were wounded in attacks against nightclub venues. CONCLUSIONS: While terrorist attacks against nightclub venues are infrequent, the risk for mass casualties and injuries can be significant, mainly when explosives and armed assaults are used.


Asunto(s)
Incidentes con Víctimas en Masa , Terrorismo , Humanos , Europa (Continente)
10.
J Ethnopharmacol ; 322: 117645, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38147942

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Morus alba L. (mulberry) is a well-known medicinal species that has been used by herbalist doctors for the treatment of diabetes for a long history, and modern ethnopharmacological studies have demonstrated the ameliorating effects of different mulberry extracts toward diabetes-related symptoms and identified a number of α-glucosidase inhibitors as hypoglycemic ingredients. AIM OF THE STUDY: The present study aims to explore new potent α-glucosidase inhibitors from the root bark of M. alba (known as Sang-Bai-Pi in traditional medicine) based on an in vivo antidiabetic evaluation of its extract fractions and further characterize the preliminary mechanism of the new active constituents. MATERIALS AND METHODS: α-Glucosidase inhibitory assay and diabetic mice model were used to locate and evaluate the active fractions from the extract. Diverse separation techniques (e.g. Sephadex LH-20 column chromatograph (CC) and HPLC) and spectroscopic methods (e.g. MS, NMR and ECD) were employed to isolate and structurally characterize the obtained constituents, respectively. Fluorescence quenching, kinetics and molecular docking experiments were conducted to investigate the enzyme inhibitory mechanism of the active compounds. RESULTS: The 80% ethanol eluate from the macroporous resin CC exerted good antidiabetic effects in the tested mice. Fifty-two flavonoids including 22 new ones were then separated and identified, and most of them showed strong inhibition against α-glucosidase with their structure-activity relationship being also discussed. The four new most active ingredients were further characterized to be mixed type of α-glucosidase inhibitors, and their binding modes with the enzyme were also explored. CONCLUSIONS: Our current work has demonstrated that the root bark of M. alba is an extremely rich source of flavonoids as potent α-glucosidase inhibitors and potential antidiabetic agents, which makes it a promising candidate species to develop new natural remedies for the prevention and treatment of diabetes.


Asunto(s)
Diabetes Mellitus Experimental , Morus , Ratones , Animales , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , alfa-Glucosidasas/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Morus/química , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/química , Extractos Vegetales/uso terapéutico , Flavonoides/farmacología , Flavonoides/uso terapéutico , Flavonoides/química
11.
Phytochemistry ; 213: 113787, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37414237

RESUMEN

Eighteen previously unreported pregnane glycosides, namely marsdenosides S1-S18, along with 15 known analogues, have been isolated from the stems of Marsdenia tenacissima. The structures of the undescribed compounds were elucidated by spectroscopic means, and their absolute configurations were established on the basis of time-dependent density functional theory (TD-DFT) based electronic circular dichroism (ECD) calculation, X-ray crystallography and acid hydrolysis. All the isolates were evaluated for their chemo-reversal ability against P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in MCF-7/ADR cell line, and nine ones displayed moderate MDR reversal activity with reversal folds in the range of 2.45-9.01. The most active 12-O-acetyl-20-O-benzoyl-(14,17,18-orthoacetate)-dihydrosarcostin-3-O-ß-d-thevetopyranosyl-(1 â†’ 4)-O-ß-d-oleandropyranosyl-(1 â†’ 4)-O-ß-d-cymaropyranoside increased the sensitivity of MCF-7/ADR cell to adriamycin comparably to the reference drug verapamil (RF = 8.93).


Asunto(s)
Marsdenia , Marsdenia/química , Estructura Molecular , Glicósidos/farmacología , Glicósidos/química , Pregnanos/farmacología , Pregnanos/química , Resistencia a Múltiples Medicamentos
12.
Cell Cycle ; 22(14-16): 1777-1797, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37486005

RESUMEN

Coronavirus disease 2019 (COVID-19) is raging worldwide and causes an immense disease burden. Despite this, the biomarkers and targeting drugs of COVID-19 of differing severity remain largely unknown. Based on the GSE164805 dataset, we identified modules most critical for mild COVID-19 (mCOVID-19) and severe COVID-19 (sCOVID-19) through WGCNA, respectively. We subsequently constructed a protein-protein interaction network, and detected 16 hub genes for mCOVID-19 and 10 hub genes for sCOVID-19, followed by the prediction of upstream transcription factors (TFs) and kinases. The enrichment analysis then showed downregulation of TNFA signaling via NFKB for mCOVID-19, as well as downregulation of MYC targets V1 for sCOVID-19. Infiltration degrees of many immune cells, such as macrophages, were also sharply different between mCOVID-19 and sCOVID-19 samples. Predicted protein targeting drugs with the highest scores nearly all belong to naturally derived or synthetic glucocorticoids. For the two single-cell RNA-seq datasets, we explored the expression distribution of hub genes for mCOVID-19/sCOVID-19 in each cell type. The expression levels of PRKCA, MCM5, TYMS, RBBP4, BCL6, FLOT1, KDM6B, and TLR2 were found to be cell-type-specific. Furthermore, the expression levels of 10 hub genes for mCOVID-19 were significantly upregulated in PBMCs between eight healthy controls and eight mCOVID-19 patients at our institution. Collectively, we detected critical modules, pathways, TFs, kinases, immune cells, targeting drugs, hub genes, and their expression distributions in different cell types that may involve the pathogenesis of COVID-19 of differing severity, which may propel earlier diagnosis and more effective treatment of this intractable disease in the future.


Asunto(s)
COVID-19 , Humanos , COVID-19/genética , Regulación hacia Abajo , Sistemas de Liberación de Medicamentos , Glucocorticoides , Análisis de Datos , Histona Demetilasas con Dominio de Jumonji
13.
Fitoterapia ; 168: 105551, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37247696

RESUMEN

Twenty compounds comprising four pregnane steroids (2-4 & 20) and 16 pregnane glycosides (1 & 5-19) have been obtained from the ethanol extract of the roots of a Dai ethnological herb, Marsdenia tenacissima. Their structures were characterized on the basis of comprehensive spectroscopic analyses with 17 ones (1-17) being reported for the first time, including the rare cases (2 & 3) of free C21 steroids with 17α-acetyl substitution, compounds 4-7 bearing an unusual 14α-OH, and the first examples with simultaneous 14α-OH/17α-acetyl substitution (7) and glycosylation at C-12 position (10 & 11). An empirical rule for the identification of C-17 configuration, in C21 steroids incorporating the marsdenin constitution structure, was also proposed. All the isolates, along with an array of previously reported analogues in our compound library, were screened for their chemo-reversal ability against P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in MCF-7/ADR cell line, and six compounds exhibited moderate MDR reversal activity with reversal folds ranging from 1.92 to 4.44.


Asunto(s)
Marsdenia , Marsdenia/química , Estructura Molecular , Esteroides/farmacología , Esteroides/química , Pregnanos/farmacología , Pregnanos/química , Glicósidos/farmacología , Glicósidos/química , Resistencia a Múltiples Medicamentos
14.
Food Funct ; 14(4): 2223-2238, 2023 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-36757840

RESUMEN

Probiotic Enterococcus hirae WEHI01 and Enterococcus faecium WEFA23 from infants were previously found to effectively inhibit the development of melanoma. In this study, their immunomodulatory and antitumor mechanisms were systemically studied. In vitro assay showed that E. hirae WEHI01 and E. faecium WEFA23 achieved biphasic immune regulation, which was revealed by the activation of resting spleen lymphocytes and RAW264.7 macrophages, as well as the anti-inflammation effect when immune cells were treated with LPS. The antitumor effects of E. hirae WEHI01 and E. faecium WEFA23 in vitro and vivo were then investigated. CCK8 and the cell scratch assay showed that the conditioned media, which were co-incubated with Enterococcus and spleen lymphocytes, significantly inhibited the proliferation and migration of B16F10, HepG-2 and HT-29 cells. The results of the tumor-bearing mice model experiment showed that E. faecium WEFA23 inhibition of the growth of tumors in mice, and the anti-tumor mechanism involved three aspects, namely tumor proliferation (decreasing expressions of LDHA, VEGF, MMP2, MMP9 and HIF-1α), inhibition of the pro-inflammation state (decreasing expressions of IL-6, TGF-ß and IL-17) and the promotion of apoptosis (increasing expression of Bax/Bcl-2, caspase-3 and p53). The results suggest that the two strains of Enterococcus could be promising candidates for treating melanoma with a highly inhibitory effect.


Asunto(s)
Enterococcus faecium , Melanoma , Ratones , Animales , Enterococcus , Enterococcus faecium/fisiología , Apoptosis , Proliferación Celular
15.
Health Secur ; 21(2): 141-145, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36629863

RESUMEN

Firefighters are a critical component of the emergency response system and therefore a potential target for organizations seeking to disrupt this system. Terrorist organizations may deliberately attack firefighters to both increase the devastation of an attack and impair the affected community's ability to respond to an attack. We performed a focused search of the Global Terrorism Database to identify terrorist attacks against firefighters worldwide. The database includes incidents from 1970 through 2019, with a total of 201,183 entries. These entries were searched for incidents involving firefighters or fire trucks. We analyzed trends in the number of incidents occurring per year, regions of the world impacted, methods employed, and number of casualties inflicted. A total of 42 attacks involving firefighters were identified in the Global Terrorism Database resulting in 26 deaths and 95 wounded. Of the 42 attacks, 12 (28.6%) were secondary attacks, where firefighters responding to an initial attack were themselves targeted. The most common method for both primary and secondary attacks was the use of a bomb or explosive. Although attacks against firefighters are uncommon, they highlight both the strategic value and vulnerability of firefighters to terrorist attacks. Increased efforts must be made to protect firefighters from future terrorist attacks.


Asunto(s)
Bomberos , Terrorismo , Humanos
16.
Foods ; 12(1)2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36613392

RESUMEN

The health benefits of Vaccinium bracteatum are well recorded in ancient Chinese medical books and were also demonstrated by modern researches. However, the relationship between its beneficial functions and specific chemical constituents has not been fully characterized. This study investigated the bioactive small-molecule constituents in the leaves of V. bracteatum, which afforded 32 compounds including ten new ones (1-9) and ten pairs of enantiomers (9-18). Their structures with absolute configurations were elucidated by spectroscopic methods, especially nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) analyses, with 1-4 bearing a novel revolving-door shaped scaffold. While half-compounds exhibited decent antioxidant activity by scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals, all except 19 and 20 exerted significant capturing activity against diammonium 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) radicals. In addition, the new iridoids 1, 5, 6, and 7 exerted apparent neuroprotective activity toward PC12 cells, with 1 being comparable to the positive control, and selective compounds also displayed anti-diabetic and anti-inflammatory properties by inhibiting α-glucosidase and NO production, respectively. The current work revealed that the bioactive small-molecule constituents could be closely related to the functional food property of the title species.

17.
Sci Total Environ ; 863: 160913, 2023 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-36529393

RESUMEN

Wetland soil denitrification removes excess inorganic nitrogen (N) and prevents eutrophication in aquatic ecosystems. Wetland plants have been considered the key factors determining the capacity of wetland soil denitrification to remove N pollutants in aquatic ecosystems. However, the influences of various plant communities on wetland soil denitrification remain unknown. In the present study, we measured variations in soil denitrification under different herbaceous plant communities including single Phragmites karka (PK), single Paspalum thunbergia (PT), single Zizania latifolia (ZL), a mixture of Paspalum thunbergia plus Phragmites karka (PTPK), a mixture of Paspalum thunbergia plus Zizania latifolia (PTZL), and bare soil (CK) in the Estuary of Nantiaoxi River, the largest tributary of Qingshan Lake in Hangzhou, China. The soil denitrification rate was significantly higher in the surface (0-10 cm) than the subsurface (10-20 cm) layer. Wetland plant growth increased the soil denitrification rate by significantly increasing the soil water content, nitrate concentration, and ln(nirS) + ln(nirK). A structural equation model (SEM) showed that wetland plants indirectly regulated soil denitrification by altering the aboveground and belowground plant biomass, nitrate concentration, abundances of denitrifying functional genes, and denitrification potential. There was no significant difference in soil denitrification rates among PT, PK and ZL. The soil denitrification rate was significantly lower in PTZL than PTPK. Two-plant communities did not necessarily enhance the denitrification rate compared to single planting, the former had a greater competitiveness on N uptake and consequently reduced the amount of nitrate available for denitrification. As PTPK had the highest denitrification rate, co-planting P. thunbergia and P. karka could effectively improve N removal efficiency and help mitigate eutrophication in adjacent aquatic ecosystems. The results of this investigation provide useful information guiding the selection of appropriate wetland herbaceous plant species for wetland construction and the removal of N pollutants in aquatic ecosystems.


Asunto(s)
Contaminantes Ambientales , Humedales , Ecosistema , Nitratos , Desnitrificación , Plantas , Suelo/química , Poaceae , Microbiología del Suelo , Nitrógeno
18.
Fitoterapia ; 164: 105354, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36403943

RESUMEN

Chemical fractionation of the EtOH extract of the roots of a traditional Chinese herb, Morinda officinalis, afforded an array of methyl 2-naphthoate derivatives (1-9) including four pairs of enantiomers (1-4), two pimarane diterpenes and two ursane triterpenoids. Among them, eight compounds (1a/1b-3a/3b, 11 and 13) were reported in the current work for the first time. The structures of the new compounds, including their absolute configurations, were defined by spectroscopic analyses in combination with quantum chemical electronic circular dichroism (ECD) and gauge-independent atomic orbital (GIAO) NMR calculations. All the isolates were evaluated for their inhibitory effect on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells, and the enantiomers 1a and 3b exhibited moderate activity with IC50 values of 41.9 and 26.2 µM. Meanwhile, compound 3b also dose-dependently inhibited the secretion of two pro-inflammatory cytokines TNF-α and IL-6 in the same cell model.


Asunto(s)
Morinda , Rubiaceae , Animales , Ratones , Morinda/química , Estructura Molecular , Antiinflamatorios/farmacología , Extractos Vegetales/química , Óxido Nítrico
19.
Environ Technol ; 44(8): 1145-1155, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34666628

RESUMEN

The effects of the addition of EDTA-2Na on sludge disintegration and phosphorus (P) migration during anaerobic fermentation (AF) of waste activated sludge (WAS) are investigated. The efficiency of sludge disintegration was positively correlated with the dose of EDTA-2Na from 0.5-2.0 g/g SS, and an enormous quantity of P was liberated into the aqueous phase, accompanied by sludge disintegration. The proper dose of EDTA-2Na for P release from WAS was 1.5 g/g SS, with an orthophosphate concentration of 394.72 mg/L. P release was more consistent with the pseudo second-order kinetic model. The migration of P species during AF with EDTA-2Na addition was also studied. Orthophosphate was the main species in both of the liquid phase and the loosely bound extracellular polymeric substances (EPS), but organic P (OP) was much more abundant in tightly bound EPS. Inorganic P (IP) was the dominant P speciation in the solid and was mainly distributed in the fraction of non-apatite IP, which accounted for more than 62.8% of IP in the presence of EDTA-2Na. In addition, both IP and OP in the solid contributed to the accumulation of P and the former was outperformed. Furthermore, the increased total dissolved P mainly came from cells. However, the fermented sludge tended to be smaller and to have low compressibility, which is detrimental to its further treatment.


Asunto(s)
Fósforo , Aguas del Alcantarillado , Fermentación , Anaerobiosis , Ácido Edético , Fosfatos , Eliminación de Residuos Líquidos
20.
Phytochemistry ; 205: 113506, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36347308

RESUMEN

Eleven undescribed glycosylated C21 steroids and nine known homologous glycosides with diverse acyl substituents, as well as their common steroid aglycone, have been obtained from the roots of Marsdenia tenacissima. Their structures were elucidated mainly by comprehensive spectroscopic analyses and comparison with previously reported analogues, with the absolute configuration assignment being supported by chemical degradation, X-ray crystallography and ECD exciton chirality method. Among them, two pairs of regioisomers were found to exist as inseparable equilibrium mixtures due to an interesting intramolecular transesterification, and nicotinoyl substitution was first reported for metabolites from the title plant. Screening of these compounds in a panel of bioassays revealed that two glycosides displayed mild inhibition against butyrylcholinesterase.


Asunto(s)
Marsdenia , Butirilcolinesterasa , Esteroides/farmacología
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