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1.
J Am Chem Soc ; 146(40): 27779-27793, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39316519

RESUMO

Sonopiezoelectric therapy harnesses piezoelectric materials to efficiently generate destructive reactive oxygen species when exposed to ultrasound. This innovative approach shows promise for tumor treatment by combining precise targeting of tumor sites through noninvasive ultrasound control with high reactive oxygen species generation capabilities via the piezoelectric effect. This study utilizes a theoretical-guided method to manipulate atomic vacancy defects and regulate the Peierls distortion in 1T'-ReS2 nanosheets, thereby imparting them with sonopiezoelectric properties not inherent to the original material. Furthermore, the plentiful unsaturated sites of ReS2 nanosheets endow them with excellent catalase- and peroxidase-mimicking activities. The reactive oxygen species generation by the engineered ReS2 nanosheets also leads to the depletion of glutathione. These capabilities are leveraged for tumor ferroptosis therapy via the classical pathway involving the 7-member 11-glutathione-GPX4 signaling axis, alongside the downregulation of dihydroorotate dehydrogenase and ferritin levels and the upregulation of fatty acid CoA ligase 4 expression. This showcases the innovative approach and potential applications of employing 1T'-ReS2 nanosheets in cancer treatment through theoretical design and materials engineering.


Assuntos
Ferroptose , Nanoestruturas , Ferroptose/efeitos dos fármacos , Humanos , Nanoestruturas/química , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/diagnóstico por imagem
2.
Rev Cardiovasc Med ; 25(2): 42, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39077336

RESUMO

Background: To identify the decrease in estimated glomerular filtration rate (eGFR) as an independent risk factor associated with ventricular tachyarrhythmias (VTA). Methods: This retrospective file review collected information from patients diagnosed with acute myocardial infarction (AMI), with and without VTA, from January 2017 to December 2019. We first applied the chi-square test to assess 12 risk factors and one outcome variable (incident rate of VTA). Next, all the 12 risk factors were further adjusted using the propensity score matching (PSM) method to simulate the dataset as a randomized controlled cohort, which can reduce the defects derived from confounding factors and the imbalance in baseline characteristics. To investigate the relationship between eGFR and VTA, univariate logistic regression analysis was applied to the cohort before and after PSM analysis. Results: A total of 503 patients diagnosed as AMI were included in the study. There were eight of twelve risk factors in baseline characteristics with a p-value < 0.05, as determined by the chi-square test before PSM matching. The result of PSM analysis indicated that 86 of 91 patients with decreased eGFR were matched, and all the risk factors were not significantly different (p-value > 0.05). The incident rates of VTA in the two groups were still significantly different (p-value < 0.001) according to the Pearson chi-square test in the cohort after PSM analysis. The results of univariate (eGFR) logistic regression indicated that the odds ratio of the cohort was 6.442 (95% confidence interval = 3.770-11.05) and 3.654 (95% confidence interval = 1.764-7.993) before and after PSM analysis respectively. Conclusions: The decrease in eGFR ( < 60 mL/min/1.73 m 2 ) has been demonstrated as an independent risk factor for VTA after AMI.

3.
Environ Sci Technol ; 58(43): 19277-19288, 2024 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-39401941

RESUMO

Short-range-ordered minerals like ferrihydrite often bind substantial organic carbon (OC), which can be altered if the minerals transform. Such mineral transformations can be catalyzed by aqueous Fe(II) (Fe(II)aq) in redox-dynamic environments like coastal wetlands, which are inundated with seawater during storm surges or tidal events associated with sea-level rise. Yet, it is unknown how seawater salinity will impact Fe(II)-catalyzed ferrihydrite transformation or the fate of bound OC. We reacted ferrihydrite with Fe(II)aq under anoxic conditions in the absence and presence of dissolved organic matter (DOM). We compared treatments with no salts (DI water), NaCl-KCl salts, and artificial seawater mixes (containing Ca and Mg ions) with or without SO42-/HCO3-. Both XRD and Mössbauer showed that NaCl-KCl favored lepidocrocite formation, whereas Ca2+/Mg2+/SO42-/HCO3- ions in seawater overrode the effects of NaCl-KCl and facilitated goethite formation. We found that the highly unsaturated and phenolic compounds (HuPh) of DOM selectively bound to Fe minerals, promoting nanogoethite formation in seawater treatments. Regardless of salt presence, only 5-9% of Fe-bound OC was released during ferrihydrite transformation, enriching HuPh relative to aliphatics in solution. This study offers new insights into the occurrence of (nano)goethite and the role of Fe minerals in OC protection in coastal wetlands.


Assuntos
Carbono , Compostos Férricos , Água do Mar , Água do Mar/química , Compostos Férricos/química , Carbono/química , Catálise , Ferro/química
4.
Environ Sci Technol ; 58(41): 18391-18403, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39360895

RESUMO

Chromium (Cr) transformation in soils mediated by iron (Fe) (oxyhr)oxides, Fe(II), organic matter (OM), and microbes is largely unexplored. Here, their coupling processes and mechanisms were investigated during anoxic incubation experiments of four Cr(VI) spiked soil samples with distinct physicochemical properties from the tropical and subtropical regions of China. It demonstrates that easily oxidizable organic carbon (EOC, 55-84%) and microbes (16-48%) drive Cr(VI) reduction in soils enriched with goethite and/or hematite, among which in dryland soils microbial sulfate reduction may also be involved. In contrast, EOC (38 ± 1%), microbes (33 ± 1%), and exchangeable and poorly crystalline Fe (oxyhr)oxide-associated Fe(II) (29 ± 3%) contribute to Cr(VI) reduction in paddy soils enriched with ferrihydrite. Additionally, exogenous Fe(II) and microbes significantly enhance Cr(VI) reduction in ferrihydrite- and goethite-rich soils, and Fe(II) greatly promotes but microbes slightly inhibit Cr passivation. Both Fe(II) and microbes, especially the latter, promote OM mineralization and result in the most substantial OM loss in ferrihydrite-rich paddy soils. During the incubation, part of the ferrihydrite converts to goethite but microbes may hinder the transformation. These results provide deep insights into the geochemical fates of redox-sensitive heavy metals mediated by the complicated effects of Fe, OM, and microbes in natural and engineered environments.


Assuntos
Cromo , Solo , Solo/química , Cromo/química , Adsorção , Poluentes do Solo/química , Ferro/química , Oxirredução , Microbiologia do Solo , Compostos Férricos/química , Minerais , Compostos de Ferro
5.
Bioorg Med Chem ; 103: 117685, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38503009

RESUMO

Genome sequencing on an intertidal zone-derived Aspergillus flavipes strain revealed its great potential to produce secondary metabolites. To activate the cryptic compounds of A. flavipes, the global regulator flLaeA was knocked out, leading to substantial up-regulation of the expression of two NRPS-like biosynthetic gene clusters in the ΔflLaeA mutant. With a scaled-up fermentation of the ΔflLaeA strain, five compounds, including two previously undescribed piperazine derivatives flavipamides A and B (1 and 2), along with three known compounds (3-5), were obtained by LC-MS guided isolation. The new compounds were elucidated by spectroscopic analysis and electronic circular dichroism (ECD) calculations, and the biosynthetic pathway was proposed on the bias of bioinformatic analysis and 13C isotope labeling evidence. This is the first report to access cryptic fungi secondary metabolites by inactivating global regulator LaeA and may provide a new approach to discovering new secondary metabolites by such genetic manipulation.


Assuntos
Aspergillus , Fungos , Aspergillus/genética , Aspergillus/metabolismo , Piperazinas/farmacologia , Piperazinas/metabolismo
6.
Neuroradiology ; 66(3): 443-455, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38183426

RESUMO

BACKGROUND: Optimal lumbar puncture segment selection remains controversial. This study aims to analyze anatomical differences among L3-4, L4-5, and L5-S1 segments across age groups and provide quantitative evidence for optimized selection. METHODS: 80 cases of CT images were collected with patients aged 10-80 years old. Threedimensional models containing L3-S1 vertebrae, dural sac, and nerve roots were reconstructed. Computer simulation determined the optimal puncture angles for the L3-4, L4-5, and L5-S1 segments. The effective dural sac area (ALDS), traversing nerve root area (ATNR), and area of the lumbar inter-laminar space (ALILS) were measured. Puncture efficacy ratio (ALDS/ALILS) and nerve injury risk ratio (ATNR/ALILS) were calculated. Cases were divided into four groups: A (10-20 years), B (21-40 years), C (41-60 years), and D (61-80 years). Statistical analysis was performed using SPSS. RESULTS: 1) ALDS was similar among segments; 2) ATNR was greatest at L5-S1; 3) ALILS was greatest at L5-S1; 4) Puncture efficacy ratio was highest at L3-4 and lowest at L5-S1; 5) Nerve injury risk was highest at L5-S1. In group D, L5-S1 ALDS was larger than L3-4 and L4-5. ALDS decreased after age 40. Age variations were minimal across parameters. CONCLUSION: The comprehensive analysis demonstrated L3-4 as the optimal first-choice segment for ages 10-60 years, conferring maximal efficacy and safety. L5-S1 can serve as an alternative option for ages 61-80 years when upper interspaces narrow. This study provides quantitative imaging evidence supporting age-specific, optimized lumbar puncture segment selection.


Assuntos
Vértebras Lombares , Punção Espinal , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Simulação por Computador , Vértebras Lombares/diagnóstico por imagem , Região Lombossacral , Tomografia Computadorizada por Raios X
7.
J Nat Prod ; 87(5): 1401-1406, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38634860

RESUMO

An unprecedented di-seco-indole diterpenoid, peniditerpenoid A (1), and a rare N-oxide-containing indole diterpenoid derivative, peniditerpenoid B (2), together with three known ones (3-5), were obtained from the mangrove-sediment-derived fungus Penicillium sp. SCSIO 41411. Their structures were determined by the analysis of spectroscopic data, quantum chemical calculations, and X-ray diffraction analyses. Peniditerpenoid A (1) inhibited lipopolysaccharide-induced NF-κB with an IC50 value of 11 µM and further effectively prevented RANKL-induced osteoclast differentiation in bone marrow macrophages. In vitro studies demonstrated that 1 exerted significant inhibition of NF-κB activation in the classical pathway by preventing TAK1 activation, IκBα phosphorylation, and p65 translocation. Furthermore, 1 effectively reduced the level of NFATc1 activation, resulting in the attenuation of osteoclast differentiation. Our findings suggest that 1 holds promise as an inhibitor with significant potential for the treatment of diseases related to osteoporosis.


Assuntos
Diferenciação Celular , Diterpenos , Indóis , NF-kappa B , Osteoclastos , Penicillium , Penicillium/química , Osteoclastos/efeitos dos fármacos , Diterpenos/farmacologia , Diterpenos/química , Diterpenos/isolamento & purificação , Animais , Camundongos , Diferenciação Celular/efeitos dos fármacos , Estrutura Molecular , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Indóis/farmacologia , Indóis/química , Ligante RANK/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos
8.
J Nat Prod ; 87(10): 2408-2420, 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39356676

RESUMO

Fourteen previously undescribed sesterterpenoids (1-14) were isolated from Bipolaris maydis. Their structures with absolute configurations were elucidated by NMR, HRESIMS, DP4+ calculations, ECD calculations, single-crystal X-ray diffraction analyses, and the modified Mosher's method. Compounds 1-5 possess an uncommon 5/11 bicyclic ring system identified from B. maydis for the first time. Compounds 6-14 have a 5/8/5 tricyclic ring system, and these compounds both possess carbonyl groups in ring A. Compound 10 showed significant reversal of paclitaxel resistance in cancer cells.


Assuntos
Bipolaris , Sesterterpenos , Sesterterpenos/farmacologia , Sesterterpenos/química , Sesterterpenos/isolamento & purificação , Estrutura Molecular , Humanos , Bipolaris/efeitos dos fármacos , Cristalografia por Raios X , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Paclitaxel/farmacologia
9.
J Nat Prod ; 87(8): 1921-1929, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39033406

RESUMO

Nine new oligophenalenone dimers, adpressins A-G (1-9), together with nine known compounds (10-18), were isolated from the fungus Talaromyces adpressus. Their chemical structures were determined on the basis of spectroscopic and mass spectral analyses. Their relative and absolute configurations were identified by 1H and 13C NMR calculations followed by DP4+ analyses, electronic circular dichroism (ECD) calculations, and ECD spectra comparison with related compounds. Compound 1 is the first example of a duclauxin derivative featuring an unusual 6/6/6/5/6/6/6 ring system, while compounds 6 and 7 contained a novel pyrrolidine ring. Compounds 5, 9, and 18 exhibited moderate inhibition against LPS-induced B lymphocyte proliferation with IC50 values ranging from 1.6 to 8.6 µM. Additionally, compounds 9 and 18 exhibited moderate inhibition against Con A-induced T lymphocyte proliferation with IC50 values of 9.3 and 2.6 µM, respectively.


Assuntos
Talaromyces , Talaromyces/química , Estrutura Molecular , Fenalenos/farmacologia , Fenalenos/química , Fenalenos/isolamento & purificação , Animais , Camundongos , Linfócitos T/efeitos dos fármacos , Linfócitos B/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos
10.
J Nat Prod ; 87(8): 1965-1974, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39051441

RESUMO

Twelve previously undescribed ophiobolin-type sesterterpenoids, undobolins A-L (1-12), were isolated from Aspergillus undulatus, and their structures were elucidated by spectroscopic analysis, ECD calculations, and single-crystal X-ray diffraction experiments. Compound 1 was the second example of 20-nor-ophiobolin reported, while compounds 2-6 were notable for oxygenation of C-2, and compound 6 showed significant inhibitory activity against ConA-induced T lymphocyte proliferation with an IC50 value of 2.3 µM, which suggests a promising new direction in the quest for immunosuppressive agents.


Assuntos
Aspergillus , Sesterterpenos , Sesterterpenos/farmacologia , Sesterterpenos/química , Sesterterpenos/isolamento & purificação , Aspergillus/química , Estrutura Molecular , Animais , Linfócitos T/efeitos dos fármacos , Cristalografia por Raios X , Imunossupressores/farmacologia , Imunossupressores/química , Imunossupressores/isolamento & purificação , Camundongos , Proliferação de Células/efeitos dos fármacos
11.
J Nat Prod ; 87(4): 753-763, 2024 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-38372239

RESUMO

In this study, we isolated lovastatin derivatives, including aculeatiols A-G (1-7) and three known compounds (8-10), from Aspergillus aculeatus. Their structures and absolute configurations were experimentally determined by high-resolution electrospray ionization mass spectrometry, nuclear magnetic resonance spectroscopy, and X-ray diffraction analyses, and the results were corroborated by quantum-chemical calculations. As members of the lovastatin derivatives, aculeatiols A-C (1-3) possess a γ-lactone functional group in the side chain. Compound 6 represents the first example that features an undescribed aromatized heterotetracyclic 6/6/6/6 ring system. Biologically, the lipid-lowering effects of all of these compounds were evaluated by analyzing the free fatty acid-induced intracellular lipid accumulation. In addition, compound 5, which regulated the transcription of genes associated with lipid uptake and synthesis, inhibited the accumulation of lipids.


Assuntos
Aspergillus , Lovastatina , Aspergillus/química , Lovastatina/farmacologia , Lovastatina/química , Estrutura Molecular , Humanos
12.
J Nat Prod ; 87(7): 1808-1816, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-38943602

RESUMO

Four new p-terphenyl derivatives, talaroterphenyls A-D (1-4), together with three biosynthetically related known ones (5-7), were obtained from the mangrove sediment-derived Talaromyces sp. SCSIO 41412. Compounds 1-3 are rare p-terphenyls, which are completely substituted on the central benzene ring by oxygen atoms; this is the first report of their isolation from natural sources. Their structures were elucidated through NMR spectroscopy, HRESIMS, and X-ray diffraction. Genome sequence analysis revealed that 1-7 were biosynthesized from tyrosine and phenylalanine, involving four key biosynthetic genes (ttpB-ttpE). These p-terphenyls (1-7) and 36 marine-derived terphenyl analogues (8-43) were screened for phosphodiesterase 4 (PDE4) inhibitory activities, and 1-5, 14, 17, 23, and 26 showed notable activities with IC50 values of 0.40-16 µM. The binding pattern of p-terphenyl inhibitors 1-3 with PDE4 were explored by molecular docking analysis. Talaroterphenyl A (1), with a low cytotoxicity, showed obvious anti-inflammatory activity in LPS-stimulated RAW264.7 cells. Furthermore, in the TGF-ß1-induced medical research council cell strain-5 (MRC-5) pulmonary fibrosis model, 1 could down-regulate the expression levels of FN1, COL1, and α-SMA significantly at concentrations of 5-20 µM. This study suggests that the oxidized p-terphenyl 1, as a marine-derived PDE4 inhibitor, could be used as a promising antifibrotic agent.


Assuntos
Inibidores da Fosfodiesterase 4 , Compostos de Terfenil , Inibidores da Fosfodiesterase 4/farmacologia , Inibidores da Fosfodiesterase 4/química , Inibidores da Fosfodiesterase 4/isolamento & purificação , Camundongos , Animais , Compostos de Terfenil/farmacologia , Compostos de Terfenil/química , Compostos de Terfenil/isolamento & purificação , Estrutura Molecular , Talaromyces/química , Células RAW 264.7 , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Biologia Marinha
13.
Bioorg Chem ; 146: 107280, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38479131

RESUMO

Ten new compounds, including three pairs of diarylcyclopentenone enantiomers (±) talaromycesins A-C (1-3) and four biphenyl derivatives talaromycesins D-G (4-7), along with four known compounds (8-11), were isolated from the fungus Talaromyces adpressus. Their structures were determined by analyses of extensive NMR spectroscopic and HRESIMS data, and their absolute configurations were elucidated by the dimolybdenum tetraacetate [Mo2(AcO)4]-induced ECD spectra, X-ray crystallographic studies, and ECD calculations. These new compounds were evaluated for their immunosuppressive activities for the first time, and compound 7 probably exerted liver-protective and anti-inflammatory effects on Con A-induced AIH by decreasing the levels of inflammatory cytokines, modulating immune homeostasis, and decreasing hepatocyte apoptosis, which may become a potential drug for the treatment of autoimmune diseases.


Assuntos
Talaromyces , Espectroscopia de Ressonância Magnética , Talaromyces/química , Compostos de Bifenilo , Estrutura Molecular
14.
Surg Endosc ; 38(9): 4956-4964, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38977497

RESUMO

OBJECTIVE: To investigate the significance of endoscopic grading (Hill's classification) of gastroesophageal flap valve (GEFV) in the examination of patients with gastroesophageal reflux disease (GERD). METHODS: One hundred and sixty-two patients undergoing gastroscopy in the Department of Gastroenterology, Xingyi People's Hospital between Apr. 2022 and Sept. 2022 were selected by convenient sampling, and data such as GEFV grade, and findings of esophageal high-resolution manometry (HRM) and esophageal 24-h pH/impedance reflux monitoring, and Los Angeles (LA) classification of reflux esophagitis (RE) were collected and compared. RESULTS: Statistically significant differences in age (F = 9.711, P < 0.001) and hiatal hernia (χ = 35.729, P < 0.001) were observed in patients with different GEFV grades. The resting LES pressures were 12.12 ± 2.79, 10.73 ± 2.68, 9.70 ± 2.29, and 8.20 ± 2.77 mmHg (F = 4.571, P < 0.001) and LES lengths were 3.30 ± 0.70, 3.16 ± 0.68, 2.35 ± 0.83, and 2.45 ± 0.62 (F = 3.789, P = 0.011), respectively, in patients with GEFV grades I-IV. DeMeester score (Z = 5.452, P < 0.001), AET4 (Z = 5.614, P < 0.001), acid reflux score (upright) (Z = 7.452, P < 0.001), weak acid reflux score (upright) (Z = 3.121, P = 0.038), liquid reflux score (upright) (Z = 3.321, P = 0.031), acid reflux score (supine) (Z = 6.462, P < 0.001), mixed reflux score (supine) (Z = 3.324, P = 0.031), gas reflux score (supine) (Z = 3.521, P = 0.024) were different in patients with different GEFV grades, with statistically significant differences. Pearson correlation analysis revealed a positive correlation between RE grade and LA classification of GERD (r = 0.662, P < 0.001), and the severity of RE increased gradually with the increase of the Hill grades of GEFV. CONCLUSION: The Hill grade of GEFV is related to age, hiatal hernia, LES pressure, and the consequent development and severity of acid reflux and RE. Evaluation of esophageal motility and reflux based on the Hill grade of GEFV is of significance for the diagnosis and treatment of GERD.


Assuntos
Refluxo Gastroesofágico , Manometria , Humanos , Refluxo Gastroesofágico/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Manometria/métodos , Adulto , Idoso , Gastroscopia/métodos , Junção Esofagogástrica/fisiopatologia , Junção Esofagogástrica/patologia , Junção Esofagogástrica/cirurgia , Monitoramento do pH Esofágico , Hérnia Hiatal/cirurgia , Hérnia Hiatal/complicações , Esfíncter Esofágico Inferior/fisiopatologia
15.
Mar Drugs ; 22(9)2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39330265

RESUMO

Three new polyketides, including three ester derivatives (1, 3, and 5) and a new natural product, which was a benzoquinone derivative, embelin A (4), together with nine known ones (2 and 6-13), were isolated from the mangrove-derived fungus Penicillium sp. SCSIO 41411. Their structures were determined by detailed NMR and MS spectroscopic analyses. The X-ray single-crystal diffraction analysis of 4 was described for the first time. Compound 9 displayed obvious inhibition against PDE4 with an inhibitory ratio of 40.78% at 10 µM. Compound 12 showed DPPH radical scavenging activity, with an EC50 of 16.21 µg/mL, compared to the positive control (ascorbic acid, EC50, 11.22 µg/mL). Furthermore, compound 4 exhibited cytotoxicity against PC-3 and LNCaP with IC50 values of 18.69 and 31.62 µM, respectively.


Assuntos
Penicillium , Policetídeos , Penicillium/química , Policetídeos/farmacologia , Policetídeos/química , Policetídeos/isolamento & purificação , Humanos , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Cristalografia por Raios X , Estrutura Molecular
16.
Mar Drugs ; 22(9)2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39330274

RESUMO

Two new C23-steroids derivatives, cyclocitrinoic acid A (1) and cyclocitrinoic acid B (2), and a new isocoumarin metabolite, (3R,4S)-6,8-dihydroxy-3,4,5-trimethyl-7-carboxamidelisocoumarin (10), together with 12 known compounds (3-9, 11-15) were isolated from the mangrove-sediment fungus Penicillium sp. SCSIO 41429. The structures of the new compounds were comprehensively characterized by 1D and 2D NMR, HRESIMS and ECD calculation. All isolates were evaluated for pancreatic lipase (PL) inhibitory and antioxidant activities. The biological evaluation results revealed that compounds 2, 14 and 15 displayed weak or moderate inhibition against PL, with IC50 values of 32.77, 5.15 and 2.42 µM, respectively. In addition, compounds 7, 12 and 13 showed radical scavenging activities against DPPH, with IC50 values of 64.70, 48.13, and 75.54 µM, respectively. In addition, molecular docking results indicated that these compounds had potential for PL inhibitory and antioxidant activities, which provided screening candidates for antioxidants and a reduction in obesity.


Assuntos
Antioxidantes , Sedimentos Geológicos , Isocumarinas , Lipase , Simulação de Acoplamento Molecular , Penicillium , Penicillium/metabolismo , Penicillium/química , Isocumarinas/farmacologia , Isocumarinas/química , Isocumarinas/isolamento & purificação , Lipase/antagonistas & inibidores , Lipase/metabolismo , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Sedimentos Geológicos/microbiologia , Concentração Inibidora 50 , Rhizophoraceae/microbiologia , Estrutura Molecular
17.
Mar Drugs ; 22(3)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38535444

RESUMO

Two new sesquiterpenoid derivatives, elgonenes M (1) and N (2), and a new shikimic acid metabolite, methyl 5-O-acetyl-5-epi-shikimate (3), were isolated from the mangrove sediment-derived fungus Roussoella sp. SCSIO 41427 together with fourteen known compounds (4-17). The planar structures were elucidated through nuclear magnetic resonance (NMR) and mass spectroscopic (MS) analyses. The relative configurations of 1-3 were ascertained by NOESY experiments, while their absolute configurations were determined by electronic circular dichroism (ECD) calculation. Elgonene M (1) exhibited inhibition of interleukin-1ß (IL-1ß) mRNA, a pro-inflammatory cytokine, at a concentration of 5 µM, with an inhibitory ratio of 31.14%. On the other hand, elgonene N (2) demonstrated inhibition at a concentration of 20 µM, with inhibitory ratios of 27.57%.


Assuntos
Ascomicetos , Sesquiterpenos , Ácido Chiquímico/análogos & derivados , Dicroísmo Circular
18.
Eur Arch Otorhinolaryngol ; 281(9): 4963-4972, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38733533

RESUMO

BACKGROUND: Advancements in nasopharyngeal carcinoma (NPC) treatment have led to a focus on personalized treatment. Circulating tumor cells (CTCs) are important for liquid biopsies and personalized treatment but are not being fully utilized. This study examined how pre- and post-treatment CTC counts, EMT subtypes, clinical characteristics, and patient prognosis are related in order to support the use of liquid biopsy in managing NPC. METHODS: This retrospective study included 141 patients with locally advanced NPC. All patients underwent CanPatrol™ CTC detection pre- and post-treatment and were categorized into EMT subtypes: epithelial type, mixed type, and mesenchymal type. This study analyzed CTC enumeration, EMT subtypes, and their associations with clinical characteristics and survival outcomes. RESULTS: The results indicated a positive correlation between the pre-treatment detection rate of CTCs and N stage (P < 0.01), alongside a positive correlation with the TNM clinical stage (P = 0.02). Additionally, the detection rate of mesenchymal CTCs post-treatment is positively associated with the N stage (P = 0.02). The enumeration of CTCs pre- and post-treatment is negatively correlated with prognosis and has statistical significance. Additionally, an investigation into the EMT subtypes of CTCs revealed a significant association between the presence of mesenchymal CTCs pre- and post-treatment and decreased overall survival (OS) (P < 0.05). Furthermore, T stage, N stage, TNM clinical stage, and Epstein-Barr virus (EBV) DNA were also significantly correlated with OS. CONCLUSION: The study found that mesenchymal CTCs pre- and post-treatment, as well as the number of CTCs, were linked to a poor prognosis.


Assuntos
Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Estadiamento de Neoplasias , Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/patologia , Masculino , Feminino , Estudos Retrospectivos , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/terapia , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/diagnóstico , Adulto , Prognóstico , Idoso , Transição Epitelial-Mesenquimal , Biópsia Líquida/métodos
19.
Chem Biodivers ; 21(4): e202400070, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38356321

RESUMO

One new fatty acid derivative, (2E,4E)-6,7-dihydroxy-2-methylocta-2,4-dienoic acid (1), and 16 known compounds (2-17) were isolated from the mangrove sediment derived fungus Trichoderma harzianum SCSIO 41051. Their structures were established by spectroscopic methods, computational ECD, and Mo2(OAc)4-induced ECD experiment. All the compounds were evaluated for their acetylcholinesterase (AChE) and pancreatic lipase (PL) inhibition. Compounds 9 and 14 exhibited moderate AChE inhibitory activities with IC50 values of 2.49 and 2.92 µM, respectively, which compounds 8 and 9 displayed moderate inhibition on PL with IC50 value of 2.30 and 2.34 µM, respectively.


Assuntos
Hypocreales , Trichoderma , Acetilcolinesterase/metabolismo , Inibidores Enzimáticos/farmacologia , Hypocreales/química , Estrutura Molecular , Trichoderma/química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/farmacologia , Lipase/antagonistas & inibidores
20.
J Craniofac Surg ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758565

RESUMO

OBJECTIVE: To study the efficacy of ultrasound-guided parasternal block (US-PSI) in pediatric patients undergoing auricular reconstruction surgery. METHODS: For this study, the authors recruited 60 children between the ages of 5 and 12 years who underwent auricular reconstruction with autologous costal cartilage (ACC) to correct microtia. They were randomized to receive either ultrasound-guided modified parasternal block or periprostatic local infiltration anesthesia (PLIA), with 30 cases in each group. Ultrasound-guided parasternal block was administered following anesthesia induction, whereas PLIA was administered after ACC harvest. Lastly, following surgery, all children were provided with patient-controlled intravenous analgesia with sufentanil, and the numeric pain rating scale (NRS) was used to assess the intensity of pain. Our primary outcomes were the resting NRS pain scores and the NRS scores upon coughing at 1, 6, 12, 24, and 48 hours postsurgery. Sufentanil consumption within the first 24 hours of surgery, the mean duration to first ambulation, and the usage of rescue analgesics were our secondary outcomes. The authors also recorded the occurrence of undesirable side effects as well as more serious side effects like pneumothorax. RESULTS: Pediatric patients who were administered US-PSI showed significantly reduced NRS chest pain scores at 6 and 12 hours postsurgery compared to those who received PLIA (P<0.05). In addition, sufentanil consumption within the first 24 hours postsurgery, duration to first ambulation, and use of rescue analgesics were significantly lower among patients in the US-PSI group when compared to those in the PLIA group (P<0.05). CONCLUSIONS: This study found that US-PSI was a highly efficacious and safe technique for postsurgical analgesia following auricular reconstruction with ACC in pediatric patients. LEVEL OF EVIDENCE: Level II, therapeutic study.

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