RESUMEN
Tumor-stromal interactions and stromal heterogeneity in the tumor microenvironment are critical factors that influence the progression, metastasis, and chemoresistance of pancreatic ductal adenocarcinoma (PDAC). Here, we used spatial transcriptome technology to profile the gene expression landscape of primary PDAC and liver metastatic PDAC after bioactive black phosphorus nanomaterial (bioactive BP) treatment using a murine model of PDAC (LSL-KrasG12D/+; LSL-Trp53R172H/+; and Pdx-1-Cre mice). Bioinformatic and biochemical analyses showed that bioactive BP contributes to the tumor-stromal interplay by suppressing cancer-associated fibroblast (CAF) activation. Our results showed that bioactive BP contributes to CAF heterogeneity by decreasing the amount of inflammatory CAFs and myofibroblastic CAFs, two CAF subpopulations. Our study demonstrates the influence of bioactive BP on tumor-stromal interactions and CAF heterogeneity and suggests bioactive BP as a potential PDAC treatment.
Asunto(s)
Fibroblastos Asociados al Cáncer , Carcinoma Ductal Pancreático , Nanoestructuras , Neoplasias Pancreáticas , Fósforo , Animales , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Ratones , Nanoestructuras/química , Fósforo/química , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Fibroblastos Asociados al Cáncer/efectos de los fármacos , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/metabolismo , Microambiente Tumoral/efectos de los fármacos , Humanos , Línea Celular TumoralRESUMEN
Significance: Frequency-domain diffuse optical tomography (FD-DOT) could enhance clinical breast tumor characterization. However, conventional diffuse optical tomography (DOT) image reconstruction algorithms require case-by-case expert tuning and are too computationally intensive to provide feedback during a scan. Deep learning (DL) algorithms front-load computational and tuning costs, enabling high-speed, high-fidelity FD-DOT. Aim: We aim to demonstrate a simultaneous reconstruction of three-dimensional absorption and reduced scattering coefficients using DL-FD-DOT, with a view toward real-time imaging with a handheld probe. Approach: A DL model was trained to solve the DOT inverse problem using a realistically simulated FD-DOT dataset emulating a handheld probe for human breast imaging and tested using both synthetic and experimental data. Results: Over a test set of 300 simulated tissue phantoms for absorption and scattering reconstructions, the DL-DOT model reduced the root mean square error by 12 % ± 40 % and 23 % ± 40 % , increased the spatial similarity by 17 % ± 17 % and 9 % ± 15 % , increased the anomaly contrast accuracy by 9 % ± 9 % ( µ a ), and reduced the crosstalk by 5 % ± 18 % and 7 % ± 11 % , respectively, compared with model-based tomography. The average reconstruction time was reduced from 3.8 min to 0.02 s for a single reconstruction. The model was successfully verified using two tumor-emulating optical phantoms. Conclusions: There is clinical potential for real-time functional imaging of human breast tissue using DL and FD-DOT.
Asunto(s)
Algoritmos , Neoplasias de la Mama , Aprendizaje Profundo , Procesamiento de Imagen Asistido por Computador , Fantasmas de Imagen , Tomografía Óptica , Tomografía Óptica/métodos , Tomografía Óptica/instrumentación , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Neoplasias de la Mama/diagnóstico por imagen , Mama/diagnóstico por imagen , Femenino , Imagenología Tridimensional/métodosRESUMEN
Allogeneic chimeric antigen receptor (CAR)-T cells hold great promise for expanding the accessibility of CAR-T therapy, whereas the risks of allograft rejection have hampered its application. Here, we genetically engineered healthy-donor-derived, CD19-targeting CAR-T cells using CRISPR-Cas9 to address the issue of immune rejection and treated one patient with refractory immune-mediated necrotizing myopathy and two patients with diffuse cutaneous systemic sclerosis with these cells. This study was registered at ClinicalTrials.gov (NCT05859997). The infused cells persisted for over 3 months, achieving complete B cell depletion within 2 weeks of treatment. During the 6-month follow-up, we observed deep remission without cytokine release syndrome or other serious adverse events in all three patients, primarily shown by the significant improvement in the clinical response index scores for the two diseases, respectively, and supported by the observations of reversal of inflammation and fibrosis. Our results demonstrate the high safety and promising immune modulatory effect of the off-the-shelf CAR-T cells in treating severe refractory autoimmune diseases.
RESUMEN
Bogie hunting instability is one of the common faults in railway vehicles. It not only affects ride comfort but also threatens operational safety. Due to the lower operating speed of metro vehicles, their bogie hunting stability is often overlooked. However, as wheel tread wear increases, metro vehicles with high conicity wheel-rail contact can also experience bogie hunting instability. In order to enhance the operational safety of metro vehicles, this paper conducts field tests and simulation calculations to study the bogie hunting instability behavior of metro vehicles and proposes corresponding solutions from the perspective of wheel-rail contact relationships. Acceleration and displacement sensors are installed on metro vehicles to collect data, which are processed in real time in 2 s intervals. The lateral acceleration of the frame is analyzed to determine if bogie hunting instability has occurred. Based on calculated safety indicators, it is determined whether deceleration is necessary to ensure the safety of vehicle operation. For metro vehicles in the later stages of wheel wear (after 300,000 km), the stability of their bogies should be monitored in real time. To improve the stability of metro vehicle bogies while ensuring the longevity of wheelsets, metro vehicle wheel treads should be reprofiled regularly, with a recommended reprofiling interval of 350,000 km.
RESUMEN
Objective: To investigate the correlation between vibration sensory threshold (VPT) and renal function, including glomerulus and renal tubule, in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 1274 patients with T2DM who were enrolled in the Department of Endocrinology of the First Affiliated Hospital of Fujian Medical University between January 2017 and June 2020 were included. Patients were grouped according to VPT levels and divided into three groups, including the normal VPT group (VPT<15V), the mild-moderate elevated VPT group (VPT15~25V), and the severely elevated VPT group (VPT≥25 V). Linear correlation analysis was used to analyze the correlation between VPT and renal functions, including glomerulus markers urine microalbumin (MA) and urinary immunoglobulin G (U-IgG), and renal tubule marker α1-microglobulin (α1-MG). Chronic kidney disease (CKD) was defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The binary logistic regression of the relation between VPT and CKD, eGFR<60 ml/min, and UACR >30 mg/g were expressed. Results: In the mild-moderate and severely elevated VPT group, injury biomarkers of glomerulus (MA and U-IgG), renal tubule (α1-MG), and the incidence of CKD, eGFR<60 ml/min, and UACR > 30 mg/g were gradually increased compared with the normal VPT group. Furthermore, patients with diabetes and severely elevated VPT had significantly higher levels of MA (ß=197.54, p=0.042) and α1-MG (ß=11.69, p=0.023) compared to those with normal VPT. Also, patients with mild-moderate elevated VPT demonstrate significantly higher levels of MA (ß=229.02, p=0.005). Patients in mild-moderate elevated VPT group (OR=1.463, 95% CI 1.005-2.127; OR=1.816, 95% CI 1.212-2.721) and severely elevated VPT group (OR=1.704, 95% CI 1.113-2.611; OR=2.027, 95% CI 1.248-3.294) are at a higher incidence of CKD and elevated levels of UACR>30mg/g compared to those in the VPT normal group. Moreover, the incidence of positive Upro was notably higher in the severely elevated VPT group (OR=1.738, 95% CI 1.182-2.556). However, this phenomenon was not observed in the incidence of eGFR <60 ml/min. Conclusion: A higher VPT is positively associated with the incidence of CKD in patients with T2DM, particularly with elevated UACR. VPT may serve as a marker for glomerulus and renal tubule injury.
Asunto(s)
Diabetes Mellitus Tipo 2 , Umbral Sensorial , Vibración , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Umbral Sensorial/fisiología , Tasa de Filtración Glomerular , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/epidemiología , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/epidemiología , Adulto , Pruebas de Función Renal , Túbulos Renales/fisiopatología , Riñón/fisiopatologíaRESUMEN
One rare stephacidin-asperochratide hybrid, stephaochratidin A (1), was isolated from the deep-sea-derived Aspergillus ochraceus MCCC 3A00521. The relative structure of 1 was determined by comprehensive analyses of its 1D and 2D NMR data as well as HRESIMS data. And the absolute configuration was unambiguously assigned by ECD calculations and the X-ray single-crystal diffraction analysis. Plausible biosynthetic pathway of 1 was proposed. Stephaochratidin A (1) exhibited significant ferroptosis inhibitory activity with the EC50 value of 15.4 µM by downregulating HMOX-1 expression and lipid peroxidation.
Asunto(s)
Aspergillus ochraceus , Ferroptosis , Ferroptosis/efectos de los fármacos , Estructura Molecular , Aspergillus ochraceus/química , Humanos , Peroxidación de Lípido/efectos de los fármacosRESUMEN
Pinus taeda L. is a fast-growing softwood with significant commercial value. Understanding structural changes in hemicellulose during growth is essential to understanding the biosynthesis processes occurring in the cell walls of this tree. In this study, alkaline extraction is applied to isolate hemicellulose from Pinus taeda L. stem segments of different ages (1, 2, 3, and 4 years old). The results show that the extracted hemicellulose is mainly comprised of O-acetylgalactoglucomannan (GGM) and 4-O-methylglucuronoarabinoxylan (GAX), with the molecular weights and ratios (i.e., GGM:GAX) of GGM and GAX increasing alongside Pinus taeda L. age. Mature Pinus taeda L. hemicellulose is mainly composed of GGM, and the ratio of (mannose:glucose) in the GGM main chain gradually increases from 2.45 to 3.60 with growth, while the galactose substitution of GGM decreases gradually from 21.36% to 14.65%. The acetylation of GGM gradually increases from 0.33 to 0.45 with the acetyl groups mainly substituting into the O-3 position in the mannan. Furthermore, the contents of arabinose and glucuronic acid in GAX gradually decrease with growth. This study can provide useful information to the research in genetic breeding and high-value utilization of Pinus taeda L.
Asunto(s)
Pinus taeda , Polisacáridos , Polisacáridos/metabolismo , Polisacáridos/química , Pinus taeda/metabolismo , Pinus taeda/crecimiento & desarrollo , Xilanos/metabolismo , Xilanos/química , Mananos/metabolismo , Mananos/química , Peso Molecular , Pared Celular/metabolismo , Pared Celular/química , AcetilaciónRESUMEN
Three new C10 and C12 aliphatic δ-lactones (1-3), three new fatty acid methyl esters (4-6), and eight known compounds (7-14) were isolated from the marine Aureobasidium sp. LUO5. Their structures were established by detailed analyses of the NMR, HRESIMS, optical rotation, and ECD data. All isolates were tested for their inhibitory effects on nitric oxide production in LPS-induced BV-2 cells. Notably, compound 4 displayed the strongest inhibitory effect with the IC50 value of 120.3â nM.
Asunto(s)
Aureobasidium , Óxido Nítrico , Animales , Ratones , Aureobasidium/química , Aureobasidium/metabolismo , Línea Celular , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Conformación Molecular , Estructura Molecular , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Óxido Nítrico/metabolismo , LactonasRESUMEN
BACKGROUND: At present, most articles mainly focused on the diagnosis of thyroid nodules by using artificial intelligence (AI), and there was little research on the detection performance of AI in thyroid nodules. OBJECTIVE: To explore the value of a real-time AI based on computer-aided diagnosis system in the detection of thyroid nodules and to analyze the factors influencing the detection accuracy. METHODS: From June 1, 2022 to December 31, 2023, 224 consecutive patients with 587 thyroid nodules were prospective collected. Based on the detection results determined by two experienced radiologists (both with more than 15 years experience in thyroid diagnosis), the detection ability of thyroid nodules of radiologists with different experience levels (junior radiologist with 1 year experience and senior radiologist with 5 years experience in thyroid diagnosis) and real-time AI were compared. According to the logistic regression analysis, the factors influencing the real-time AI detection of thyroid nodules were analyzed. RESULTS: The detection rate of thyroid nodules by real-time AI was significantly higher than that of junior radiologist (Pâ=â0.013), but lower than that of senior radiologist (Pâ=â0.001). Multivariate logistic regression analysis showed that nodules size, superior pole, outside (near carotid artery), close to vessel, echogenicity (isoechoic, hyperechoic, mixed-echoic), morphology (not very regular, irregular), margin (unclear), ACR TI-RADS category 4 and 5 were significant independent influencing factors (all Pâ<â0.05). With the combination of real-time AI and radiologists, junior and senior radiologist increased the detection rate to 97.4% (Pâ<â0.001) and 99.1% (Pâ=â0.015) respectively. CONCLUSONS: The real-time AI has good performance in thyroid nodule detection and can be a good auxiliary tool in the clinical work of radiologists.
Asunto(s)
Inteligencia Artificial , Nódulo Tiroideo , Humanos , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/diagnóstico , Nódulo Tiroideo/patología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios Prospectivos , Anciano , Diagnóstico por Computador/métodosRESUMEN
Inverse spinel ferrimagnetic NiCo2O4(NCO) exhibits volatile physical properties due to the complex ion/valence occupation, which complicates the study its intrinsic properties. In this work, robust room temperature perpendicular magnetic anisotropy (PMA) is distinctly observed in high-quality RF-sputtered NCO film down to 3 uc (2.4 nm), confirmed by the room temperature anomalous Hall effect. The NCO films show a good metallic conductivity with a dimensional driven metal-insulator transition. The scaling relation between anomalous Hall conductivity (σxy) and the longitudinal conductivity (σxx) reveals the dirty metal behavior in conjunction with the contribution of intrinsic Berry phase or disorder-enhanced electron correlation contribute to the anomalous Hall effect for thick films while the dirty scaling law dominates for the thin films. This work introduces an oxide candidate with robust room temperature PMA as well as massive production ability for the functional spintronic applications.
RESUMEN
Eight undescribed (1-8) and 46 known compounds (9-54) were isolated from the deep-sea-derived Aspergillus sp. MCCC 3A00392. Compounds 1-3 were three novel oxoindolo diterpenoids, 4-6 were three bisabolane sesquiterpenoids, while 7 and 8 were two monocyclic cyclopropanes. Their structures were established by exhaustive analyses of the HRESIMS, NMR, and theoretical calculations of the NMR data and ECD spectra. Compounds 10, 33, 38, and 39 were able to inhibit tumor necrosis factor (TNF)-induced necroptosis in murine L929 cell lines. Functional experiments verified that compounds 10 and 39 inhibited necroptosis by downregulating the phosphorylation of RIPK3 and MLKL. Moreover, compound 39 also reduced the phosphorylation of RIPK1. Compounds 10, 33, and 34 displayed potent inhibitory activities against RSL-3 induced ferroptosis with the EC50 value of 3.0 µM, 0.4 µM, and 0.1 µM, respectively. Compound 10 inhibited ferroptosis by the downregulation of HMOX1, while compounds 33 and 34 inhibited ferroptosis through regulation of NRF2/SLC7A11/GCLM axis. However, these compounds only showed weak effect in either the necroptosis or ferroptosis relative mouse disease models. Further studies of pharmacokinetics and pharmacodynamics might improve their in vivo bioactivities.
Asunto(s)
Ferroptosis , Sesquiterpenos , Ratones , Animales , Necroptosis , Aspergillus/química , Sesquiterpenos/química , Sesquiterpenos MonocíclicosRESUMEN
The prevalence of food allergies has grown dramatically over the past decade. Recently, studies have shown the potential of marine substances to alleviate food allergies. We utilized a rat basophilic leukemia (RBL)-2H3 model to evaluate the antiallergic effects of alternariol monomethyl ether (AME) extracted from marine fungi Alternaria sp. Our results showed that AME attenuated food allergy symptoms in mice and reduced histamine release in serum. The population of mast cells in the spleen and mesenteric lymph nodes was considerably reduced. Moreover, in vitro assays also revealed that AME inhibited the release of ß-hexosaminidase and histamine. Transcriptomic analysis uncovered that AME regulated gene expression associated with mast cells. Additionally, Western blotting demonstrated that AME suppressed mast cell activation by modulating MAPK and NF-κB signaling pathways. Taken together, these findings provide a theoretical basis for the potential antiallergic use of marine-derived compounds in the development of functional foods.
Asunto(s)
Antialérgicos , Hipersensibilidad a los Alimentos , Lactonas , Ratas , Ratones , Animales , FN-kappa B/metabolismo , Ovalbúmina/metabolismo , Mastocitos , Transducción de Señal , Antialérgicos/farmacologíaRESUMEN
Ferroptosis is a newly discovered form of programmed cell death characterized by iron overload, ROS accumulation, and lipid peroxidation. It is distinguished by unique morphological, biochemical, and genetic features and stands apart from other known regulated cell death mechanisms. Studies have demonstrated a close association between ferroptosis and various cancers, including liver cancer, lung cancer, renal cell carcinoma, colorectal cancer, pancreatic cancer, and ovarian cancer. Inducing ferroptosis has shown promising results in inhibiting tumor growth and reversing tumor progression. However, the challenge lies in regulating ferroptosis in vivo due to the scarcity of potent compounds that can activate it. Integrating emerging biomedical discoveries and technological innovations with conventional therapies is imperative. Notably, considerable progress has been made in cancer treatment by leveraging immunotherapy and nanotechnology to trigger ferroptosis. This review explores the relationship between ferroptosis and emerging immunotherapies and nanotechnologies, along with their potential underlying mechanisms, offering valuable insights for developing novel cancer treatment strategies.
RESUMEN
The effects of HNK, I5, and I6 on the expression of protein in hippocampus of depressed mice were studied by isobaric tags for relative and absolute quantitation (iTRAQ) to explore the mechanism of their antidepressant action. HNK, I5, and I6 were administered intragastric administration once a day in the morning for 7 days. The drug was subsequently discontinued for 7 days (without any treatment). On the 15th day, mice in each group were given the drug (1.0, 10.0, 30.0 mg/kg) intragastric stimulation and mouse hippocampal tissues were taken to perform iTRAQ to identify differentially expressed proteins, and bioinformatics was used to analyze the functional enrichment of the differentially expressed proteins. Compared with Ctr group, the number of differentially expressed proteins in HNK, I5, and I6 treatment groups was 158, 88, and 105, respectively. The three groups shared 29 differentially expressed proteins. In addition, compared with HNK group, the number of differentially expressed proteins in I5 and I6 groups was 201 and 203, respectively. A total of 47 and 56 differentially expressed proteins were co-expressed in I5 and I6 groups. Bioinformatics analysis showed that these differentially expressed proteins mainly had the functions of binding, biocatalysis, and transport, and mainly participated in cellular process, biological regulation process, biological metabolism process, and stress reaction process. GO and KEGG pathway analysis found that these differentially expressed proteins were involved long-term potentiation, G13 pathway, platelet activation pathway, and MAPK signaling pathway. HNK, I5, and I6 antidepressants are closely related to sudden stress sensitivity, stress resistance, neurotransmitter, and metabolic pathways. This study provides a scientific basis to further elucidate the mechanism and clinical application of HNK, I5, and I6 antidepressants.
Asunto(s)
Ketamina , Proteómica , Ratones , Animales , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Antidepresivos/metabolismo , Ketamina/farmacología , Transducción de SeñalRESUMEN
PURPOSE: This study evaluated the value of contrast-enhanced ultrasonography (CEUS) in the ultrasound-guided microwave ablation (MWA) treatment of symptomatic focal uterine adenomyosis. METHODS: This retrospective study was conducted between March 2020 and January 2023, enrolling 52 patients with symptomatic focal uterine adenomyosis who had undergone MWA. All patients were examined with CEUS before and after MWA. The non-perfused volume (NPV) was compared between CEUS and dynamic contrast-enhanced magnetic resonance imaging (DCEMRI) following ablation. Therapeutic efficacy and safety were evaluated at 3-, 6-, and 12-month follow-ups. Additionally, this study explored the correlations between pre-treatment CEUS features and a volume reduction ratio indicating sufficient ablation, defined as 50% or more at the 3-month follow-up. RESULTS: No significant differences in NPV were noted between CEUS and DCE-MRI immediately after MWA and during follow-up (all P>0.05). At the 3-month follow-up, the median VRRs for the uterus and adenomyosis were 33.2% and 63.9%, respectively. Sufficient ablation was achieved in 69.2% (36/52) of adenomyosis cases, while partial ablation was observed in the remaining 30.8% (16/52). The identification of non-enhancing areas on pre-treatment CEUS was associated with sufficient ablation (P=0.016). At the 12-month follow-up, significant decreases were observed in both the uterine and adenomyosis volumes (all P<0.001). Dysmenorrhea and menorrhagia were significantly alleviated at 12 months, and no major complications were encountered. CONCLUSION: CEUS can be used to evaluate the ablation zone of focal adenomyosis that has been treated with MWA, similarly to DCE-MRI. The identification of non-enhancing areas on pretreatment CEUS indicates satisfactory treatment outcomes.
RESUMEN
Introduction: It's not clear whether there are differences in musculoskeletal damage and body composition among different age groups of type 2 diabetes. Therefore, the purpose of this study is to analyze the difference between early-onset type 2 diabetes (EOT2D) and non-early-onset type 2 diabetes (NOT2D) in musculoskeletal damage. Methods: A total of 964 patients with type 2 diabetes mellitus were selected by 1:1 propensity score matching, including 534 males and 430 females, with an average age of 52 ± 7 years and an average course of 10 ± 8.5 years. Bone mineral density and body composition were measured, and combined with biochemical tests, linear regression and binary logic regression were used to analyze the relationship between EOT2D, NOT2D and musculoskeletal damage. In addition, 414 patients with T2DM were selected according to whether they were hospitalized twice or not, and the median follow-up period was 44 months. COX survival analysis further elucidates the relationship between EOT2D, NOT2D and musculoskeletal damage. Results: Compared with patients with non-early-onset type 2 diabetes, A/G was negatively correlated with the age of onset, and had statistical significance. EOT2D has a higher risk of sarcopenia, osteoporosis and even musculoskeletal damage. With the prolongation of the course of the disease, the risk of muscle mass and/or bone mineral density decrease in EOT2D increases. Conclusion: EOT2D brings a greater risk of sarcopenia and/or osteoporosis, as well as a higher risk of reduced ASM and BMD. In addition, fat distribution may be more central.
Asunto(s)
Diabetes Mellitus Tipo 2 , Osteoporosis , Sarcopenia , Masculino , Femenino , Humanos , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/complicaciones , Sarcopenia/complicaciones , Sarcopenia/epidemiología , Edad de Inicio , Osteoporosis/epidemiología , Osteoporosis/etiología , Densidad Ósea/fisiologíaRESUMEN
A systematic investigation combined with a Global Natural Products Social (GNPS) molecular networking approach, was conducted on the metabolites of the deep-sea-derived fungus Samsoniella hepiali W7, leading to the isolation of three new fusaric acid derivatives, hepialiamides A-C (1-3) and one novel hybrid polyketide hepialide (4), together with 18 known miscellaneous compounds (5-22). The structures of the new compounds were elucidated through detailed spectroscopic analysis. as well as TD-DFT-based ECD calculation. All isolates were tested for anti-inflammatory activity in vitro. Under a concentration of 1 µM, compounds 8, 11, 13, 21, and 22 showed potent inhibitory activity against nitric oxide production in lipopolysaccharide (LPS)-activated BV-2 microglia cells, with inhibition rates of 34.2%, 30.7%, 32.9%, 38.6%, and 58.2%, respectively. Of particularly note is compound 22, which exhibited the most remarkable inhibitory activity, with an IC50 value of 426.2 nM.
Asunto(s)
Ácido Fusárico , Paecilomyces , Ácido Fusárico/farmacología , Macrófagos , Antiinflamatorios , Estructura MolecularRESUMEN
A systematic chemical investigation of the deep-sea-derived fungus Aspergillus versicolor 170217 resulted in the isolation of six new (1-6) and 45 known (7-51) compounds. The structures of the new compounds were established on the basis of exhaustive analysis of their spectroscopic data and theoretical-statistical approaches including GIAO-NMR, TDDFT-ECD/ORD calculations, DP4+ probability analysis, and biogenetic consideration. Citriquinolinones A (1) and B (2) feature a unique isoquinolinone-embedded citrinin scaffold, representing the first exemplars of a citrinin-isoquinolinone hybrid. Dicitrinones K-L (3-4) are two new dimeric citrinin analogues with a rare CH-CH3 bridge. Biologically, frangula-emodin (32) and diorcinol (17) displayed remarkable anti-food allergic activity with IC50 values of 7.9 ± 3.0 µM and 13.4 ± 1.2 µM, respectively, while diorcinol (17) and penicitrinol A (20) exhibited weak inhibitory activity against Vibrio parahemolyticus, with MIC values ranging from 128 to 256 µM.
Asunto(s)
Citrinina , Citrinina/química , Aspergillus/química , Hongos , Espectroscopía de Resonancia Magnética , Estructura MolecularRESUMEN
Three new polyketides (penidihydrocitrinins A-C, 1-3) and fourteen known compounds (4-17) were isolated from the deep-sea-derived Penicillium citrinum W17. Their structures were elucidated by comprehensive analyses of 1D and 2D NMR, HRESIMS, and ECD calculations. Compounds 1-17 were evaluated for their anti-inflammatory and anti-osteoporotic bioactivities. All isolates exhibited significant inhibitory effects on LPS-stimulated nitric oxide production in murine brain microglial BV-2 cells in a dose-response manner. Notably, compound 14 displayed the strongest effect with the IC50 value of 4.7 µM. Additionally, compounds 6, 7, and 8 significantly enhanced osteoblast mineralization, which was comparable to that of the positive control, purmorphamine. Furthermore, these three compounds also suppressed osteoclastogenesis in a dose-dependent manner under the concentrations of 2.5 µM, 5.0 µM, and 10 µM.
Asunto(s)
Penicillium , Policétidos , Animales , Ratones , Policétidos/farmacología , Policétidos/química , Estructura Molecular , Penicillium/química , Antiinflamatorios/farmacologíaRESUMEN
One new alkaloid, (S)-2-acetamido-4-(2-(methylamino)phenyl)-4-oxobutanoic acid (1), was isolated from the deep-sea-derived Penicillium citrinum XIA-16, together with 25 known compounds including ten polyketones (2-11), eight alkaloids (12-19), six steroids (20-25), and a fatty acid (26). Their planar and relative structures were determined by an analysis of 1D and 2D nuclear magnetic resonance (NMR) as well as high resolution electrospray ionization mass spectroscopy (HR-ESI-MS) data. The absolute configuration of 1 was determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Penicitrinol B (6) significantly inhibited RSL3-induced ferroptosis (EC50 =2.0â µM) by reducing lipid peroxidation and heme oxygenase 1 (HMOX1) expression. Under the concentration of 10â µM, penicitrinol A (7) was able to inhibit cuproptosis with the cell viabilities of 68.2 % compared to the negative control (copper and elesclomol) with the cell viabilities of 14.8 %.