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OBJECTIVES: The optimal dosing regimen of caspofungin in adolescents undergoing allogeneic haematopoietic stem cell transplantation against Candida spp. is unknown. The study aimed to compare body surface area (BSA)-based and fixed dosing regimens through population pharmacokinetic (PPK) analysis and to optimize dosing regimens likely to achieve therapeutic exposures. METHODS: Opportunistic sampling was used to collect plasma concentrations through a prospective observational pharmacokinetic study. PPK analysis and Monte Carlo simulations (nâ=â1000) were performed using NONMEM. RESULTS: A total of 86 samples of 30 adolescents (12-17â years old) were best described by a two-compartment pharmacokinetic model. BSA is the only covariate on clearance and central volume of distribution. For Candida glabrata and Candida albicans, a standard dosing regimen could achieve at least a 90% probability of target attainment for the indicator of AUC0-24/MIC90. Dosing regimen simulations identified a BSA cut-off value of 1.3â m2, where a fixed loading dose (LD) is preferred when BSAâ≥â1.3â m2 and a BSA-based LD is preferred when BSAâ<â1.3â m2. For maintenance dose (MD), however, the BSA-based dose was proposed, regardless of BSA. The current maximum dosing regimen of LD 70â mg/day and MD 70â mg/day could not result in sufficient antifungal exposure for Candida parapsilosis with MIC90 of 1â mg/L. Furthermore, an LD of 70â mg/day and MD of 60â mg/m2/day rendered 90.4% steady-state trough concentration (Ctrough) over 1â mg/L in the virtual population. CONCLUSIONS: Our study proposed optimized dosing regimens of caspofungin based on AUC0-24/MIC90 or Ctrough, which may support further individualized treatment.
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BACKGROUND: Oral squamous cell carcinoma (OSCC) is a frequently occurring type of head and neck cancer with a high mortality and morbidity rate. Rhopaloic acid A (RA), a terpenoid derived from sponges, has demonstrated a promising anti-tumor activity, but its effectiveness for treating OSCC remains unknown. PURPOSE: The aim of this study was to investigate whether RA inhibits the growth of OSCC. METHODS: Cell viability was evaluated using CCK-8 assays in OSCC cells (Ca9-22, HSC-3 and SAS) and in normal cells (HGF-1) treated with RA. DAPI staining, AO staining, JC-1 staining and immunofluorescence were used to determine apoptosis, mitochondrial membrane potential and autophagy in RA-treated OSCC cells. Protein expression levels were determined by western blotting. Furthermore, the anti-tumor effect of RA was confirmed in vivo using a zebrafish oral cancer xenotransplantation model. RESULTS: OSCC cells had a significantly reduced viability after RA treatment, but normal cells were not affected. Treatment with RA caused chromatin condensation in OSCC cells, which increased their expression of autophagy- and apoptosis-related proteins. Furthermore, RA caused mitochondrial damage and increased autophagosome formation. Mitophagy was also induced by RA through the JNK/BNIP3/Nix/LC3B pathway. The JNK inhibitor SP600125 prevented both RA-mediated cell death and mitophagy of OSCC cells. A zebrafish xenograft model demonstrated that RA inhibits OSCC growth. CONCLUSION: In conclusion, RA showed a potent anticancer activity in in vitro and in in vivo oral cancer models by promoting mitochondrial damage-induced apoptosis and mitophagy, which suggests that RA may be useful as a novel and effective treatment for OSCC.
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As one molecule related to cytotoxicity, surface expression of C-X3-C motif receptor 1 (CX3CR1) was highly correlated with intracellular granzyme B (GZMB) in NK and cytolytic T cells. However, the expression of CX3CR1 and GZMB in B cells has not been clarified, and their clinical significance in systemic lupus erythematosus (SLE) remains unclear. This study aimed to clarify the changes and clinical significance of peripheral blood B cells expressing GZMB and/or CX3CR1 in SLE. Peripheral blood was collected from 39 SLE patients and 48 healthy controls. We found that GZMB and CX3CR1 expression varied in different B-cell subsets, with plasmablasts possessing the highest positive percentages, consistent with bioinformatics prediction. GZMB+ and CX3CR1+ percentages in circulating B cells and plasmablasts were increased in SLE patients. CX3CR1 was upregulated on B cells after in vitro stimulation. Notch intracellular domain (NICD) expression was significantly decreased in plasmablasts of SLE patients and CX3CR1 in plasmablasts was downregulated with the addition of JAG1. In conclusion, GZMB and CX3CR1 were increased in B cells and in plasmablasts of SLE patients and CX3CR1 was negatively regulated by Notch signal in plasmablasts, which may be involved in SLE pathogenesis.
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Ligustilide is the main active component of the volatile oil from Angelica sinensis and Ligusticum chuanxiong in the Umbelliferae family. It is a phthalein compound with anti-inflammatory, analgesic, antioxidant, anti-tumor, anti-atherosclerosis, neuroprotective, and other pharmacological effects. It can improve the permeability of the blood-brain barrier and has important potential in the treatment of neurodegenerative diseases and other nervous system diseases, such as Alzheimer's disease, ischemic stroke, Parkinson's disease, vascular dementia, and depression. Therefore, the mechanism of ligustilide in the treatment of nervous system diseases was summarized to provide a reference for drug development and clinical application.
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4-Butirolactona , Enfermedades del Sistema Nervioso , Humanos , Animales , 4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacología , 4-Butirolactona/química , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
Enhanced external counterpulsation (EECP) is a treatment and rehabilitation approach for ischemic diseases, including coronary artery disease. Its therapeutic benefits are primarily attributed to the improved blood circulation achieved through sequential mechanical compression of the lower extremities. However, despite the crucial role that hemodynamic effects in the lower extremity arteries play in determining the effectiveness of EECP treatment, most studies have focused on the diastole phase and ignored the systolic phase. In the present study, a novel siphon model (SM) was developed to investigate the interdependence of several hemodynamic parameters, including pulse wave velocity, femoral flow rate, the operation pressure of cuffs, and the mean blood flow changes in the femoral artery throughout EECP therapy. To verify the accuracy of the SM, we coupled the predicted afterload in the lower extremity arteries during deflation using SM with the 0D-1D patient-specific model. Finally, the simulation results were compared with clinical measurements obtained during EECP therapy to verify the applicability and accuracy of the SM, as well as the coupling method. The precision and reliability of the previously developed personalized approach were further affirmed in this study. The average waveform similarity coefficient between the simulation results and the clinical measurements during the rest state exceeded 90%. This work has the potential to enhance our understanding of the hemodynamic mechanisms involved in EECP treatment and provide valuable insights for clinical decision-making.
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Contrapulsación , Análisis de la Onda del Pulso , Humanos , Reproducibilidad de los Resultados , Hemodinámica , Extremidad Inferior , Contrapulsación/métodosRESUMEN
Using data from single-cell RNA sequencing and flow cytometry, we initially examined the expression of FCRL3, finding it to be elevated and positively associated with TIGIT expression in the regulatory T cells of patients with systemic lupus erythematosus. This also suggests that the co-expression of FCRL3 and TIGIT warrants further attention.
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Lupus Eritematoso Sistémico , Receptores Inmunológicos , Linfocitos T Reguladores , Humanos , Receptores Inmunológicos/genética , Receptores Inmunológicos/metabolismo , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/genética , Linfocitos T Reguladores/inmunología , Regulación hacia Arriba/inmunología , Femenino , Masculino , AdultoRESUMEN
Eltrombopag was approved as a first-line treatment for patients older than 2 years old with severe aplastic anemia (SAA). However, data on eltrombopag in children with different types of aplastic anemia (AA), especially non-severe AA (NSAA), are limited. We performed a prospective, single-arm, and observational study to investigate eltrombopag's efficacy, safety, and pharmacokinetics in children with NSAA, SAA, and very severe AA (VSAA). The efficacy and safety were assessed every 3 months. The population pharmacokinetic (PPK) model was used to depict the pharmacokinetic profile of eltrombopag. Twenty-three AA children with an average age of 7.9 (range of 3.0-14.0) years were enrolled. The response (complete and partial response) rate was 12.5%, 50.0%, and 100.0% after 3, 6, and 12 months in patients with NSAA. For patients with SAA and VSAA, these response rates were 46.7%, 61.5%, and 87.5%. Hepatotoxicity occurred in one patient. Fifty-three blood samples were used to build the PPK model. Body weight was the only covariate for apparent clearance (CL/F) and volume of distribution. The allele-T carrier of adenosine triphosphate-binding cassette transporter G2 was found to increase eltrombopag's clearance. However, when normalized by weight, the clearance between the wild-type and variant showed no statistical difference. In patients with response, children with NSAA exhibited lower area under the curve from time zero to infinity, higher CL/F, and higher weight-adjusted CL/F than those with SAA or VSAA. However, the differences were not statistically significant. The results may support further individualized treatment of eltrombopag in children with AA.
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Anemia Aplásica , Benzoatos , Hidrazinas , Pirazoles , Humanos , Benzoatos/farmacocinética , Benzoatos/efectos adversos , Benzoatos/uso terapéutico , Benzoatos/administración & dosificación , Hidrazinas/farmacocinética , Hidrazinas/efectos adversos , Hidrazinas/uso terapéutico , Niño , Anemia Aplásica/tratamiento farmacológico , Pirazoles/farmacocinética , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Pirazoles/sangre , Masculino , Preescolar , Femenino , Adolescente , Estudios Prospectivos , Resultado del Tratamiento , Modelos Biológicos , Receptores de Trombopoyetina/agonistas , Índice de Severidad de la Enfermedad , Citocromo P-450 CYP3A/metabolismo , Citocromo P-450 CYP3A/genéticaRESUMEN
Diketopiperazine alkaloids have proven the most abundant heterocyclic alkaloids up to now, which usually process diverse scaffolds and rich biological activities. In our search for bioactive diketopiperazine alkaloids from marine-derived fungi, two novel diketopiperazine alkaloids, penipiperazine A (1) and its biogenetically related new metabolite (2), together with a known analogue neofipiperzine C (3), were obtained from the strain Penicillium brasilianum. Their planar structures and absolute configurations were elucidated by extensive spectroscopic analyses, 13C NMR calculation, Marfey's, ECD, and ORD methods. Compound 1 featured a unique 6/5/6/6/5 indole-pyrazino-pyrazino-pyrrolo system, and its plausible biogenetic pathway was also proposed. Additionally, compounds 1-3 have been tested for their inflammatory activities. 1 and 2 significantly inhibited the release of NO and the expression of related pro-inflammatory cytokines on LPS-stimulated RAW264.7 cells, suggesting they could be attracting candidate for further development as anti-inflammatory agent. KEY POINTS: ⢠A novel diketopiperazine alkaloid featuring a unique 6/5/6/6/5 indole-pyrazino-pyrazino-pyrrolo system was isolated from the marine fungus Penicillium brasilianum. ⢠The structure of 1 was elucidated by detailed analysis of 2D NMR data, 13C NMR calculation, Marfey's, ECD, and ORD methods. ⢠Compounds 1 and 2 significantly inhibited the release of NO and the expression of related pro-inflammatory cytokines on LPS-stimulated RAW264.7 cells.
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Alcaloides , Penicillium , Dicetopiperazinas/farmacología , Lipopolisacáridos , Hongos , Alcaloides/química , Indoles , Antiinflamatorios/farmacología , Citocinas , Estructura Molecular , Alcaloides Indólicos/farmacología , Alcaloides Indólicos/químicaRESUMEN
Twisted double bilayer graphene (tDBG) has emerged as a rich platform for studying strongly correlated and topological states, as its flat bands can be continuously tuned by both a perpendicular displacement field and a twist angle. Here, we construct a phase diagram representing the correlated and topological states as a function of these parameters, based on measurements of over a dozen tDBG devices encompassing two distinct stacking configurations. We find a hierarchy of symmetry-broken states that emerge sequentially as the twist angle approaches an apparent optimal value of θ ≈ 1.34°. Nearby this angle, we discover a symmetry-broken Chern insulator (SBCI) state associated with a band filling of 7/2 as well as an incipient SBCI state associated with 11/3 filling. We further observe an anomalous Hall effect at zero field in all samples supporting SBCI states, indicating spontaneous time-reversal symmetry breaking and possible moiré unit cell enlargement at zero magnetic field.
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Co-culturing the marine-derived fungi Penicillium janthinellium with Paecilomyces formosus led to the isolation of nine new indole-diterpenes, janthinellumines A-I (1-9), along with twelve known analogues (10-21). The chemical structures including their absolute configurations of them were assigned by the analysis of extensive spectroscopic data and calculated ECD and VCD methods. These indole-diterpenoids displayed extensive biological activities, including anti-influenza A virus, protein tyrosine phosphatase (PTP) inhibitory, and anti-Vibrio activities. Among them, the anti-influenza mechanism of compounds 1, 2, and 7 was further investigated using neuraminidase inhibitory assay, molecular docking, and reverse genetics methods, suggesting that 1, 2, and 7 could interact with Arg371 of the viral neuraminidase. The structure-activity relationship (SAR) of PTPs inhibitory activity for indole-diterpene derivatives (1, 2, 4, 5, 9-16, and 19-21) was also summarized.
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Diterpenos , Paecilomyces , Penicillium , Simulación del Acoplamiento Molecular , Técnicas de Cocultivo , Neuraminidasa/metabolismo , Indoles/química , Penicillium/química , Paecilomyces/metabolismo , Diterpenos/química , Estructura MolecularRESUMEN
Two pairs of new dimeric diketopiperazine alkaloids, ( ±)-dibrevianamides Q1 and Q2 (( ±)-1 and ( ±)-2), together with seven previously reported analogues (( ±)-3, 4-6, and ( ±)-7) were obtained from a marine-derived fungus Aspergillus sp. The structures of ( ±)-1 and ( ±)-2 were clarified using comprehensive spectroscopic analyses, the calculated ECD, and DP4 + probability methods. Speculated from the biogenesis, ( ±)-dibrevianamides Q1 and Q2 (( ±)-1 and ( ±)-2) might be the key precursor of [2 + 2] diketopiperazine dimers (( ±)-3). Compounds ( +)-1 and ( -)-2 displayed anti-H1N1 virus activity with IC50 values of 12.6 and 19.5 µM. Compound ( +)-1 showed significant activity against Mycobacterium tuberculosis (MIC, 10.2 µg/mL). KEY POINTS: ⢠Two pairs of new dimeric diketopiperazine alkaloids were obtained from the marine-derived fungus Aspergillus sp. ⢠The structures of the new compounds were clarified using comprehensive spectroscopic analyses, the calculated ECD, and DP4 + probability methods. ⢠( ±)-Dibrevianamides Q1 and Q2 were speculated to be the key precursor of [2 + 2] diketopiperazine dimers ( ±)-asperginulin A.
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Alcaloides , Hongos , Estructura Molecular , Hongos/química , Aspergillus/química , Dicetopiperazinas/farmacología , Alcaloides/farmacología , Alcaloides/químicaRESUMEN
OBJECTIVE: To investigate the expression of layilin (LAYN) in human circulating monocytes and lymphocytes and its clinical significance in systemic lupus erythematosus (SLE). METHODS: Blood samples were collected from 51 SLE patients and 50 healthy controls. Flow cytometry was used to analyze LAYN in lymphocytes and monocyte subsets. Functionally characterized molecules including human HLA, CD74 and CD62L were studied in LAYN+ monocytes. A correlation analysis was conducted between LAYN-related subsets and clinical indicators of SLE such as anti-double-stranded DNA and complements levels. ROC curves were used to explore the potential clinical diagnostic value of LAYN in SLE. RESULTS: LAYN was significantly higher in monocytes than in lymphocytes and higher in CD14+CD16+ monocytes than in CD14-CD16+ and CD14+CD16- monocytes. CD74 was upregulated and CD62L was downregulated in LAYN+ monocytes compared with LAYN- monocytes. The absolute number of LAYN+ monocytes was increased in SLE patients, and the median fluorescence intensity of HLA was decreased. LAYN+ monocytes were positively correlated with complement C4, while decreased CD62L+ percentages in LAYN+ monocytes were negatively correlated with C4. The ROC analysis revealed that the area under the curve (AUCs) for CD62L+ percentages in LAYN+ monocytes, LAYN+ lymphocyte numbers, and LAYN+ monocyte numbers to distinguish SLE from healthy individuals were 0.6245, 0.6196 and 0.6173, respectively. CONCLUSION: LAYN is differentially expressed in monocytes and their subpopulations and has corresponding functional differences. Changes in LAYN expression on monocytes are associated with complement C4 levels in SLE patients. These suggest that LAYN may be involved in the pathogenesis of SLE. ABBREVIATION: ANOVA: analysis of variance; anti-dsDNA: anti-double-stranded DNA; anti-ENA: anti-extractable nuclear antigen; anti-SSA: anti-Sjogren syndrome A; anti-SSB: anti-Sjogren syndrome B; anti-U1RNP: anti-U1 ribonucleoprotein; AUC: area under the ROC curve; CBC: complete blood count; CD62L: L-selectin; CD74/Ii: MHC class II invariant chain; CD44/HCAM: homing cell adhesion molecule; cMos: classical monocytes; CRP: C-reactive protein; CXCR2: C-X-C motif chemokine receptor 2; CXCR4: C-X-C motif chemokine receptor 4; ESR: erythrocyte sedimentation rate; HCs: healthy controls; HA: hyaluronan; HLA: human leukocyte antigen; Ig: immunoglobulin; iMos: intermediate monocytes; LAYN: layilin; MFI: median fluorescence intensity; MIF: migration inhibitory factor; ncMos: nonclassical monocytes; PBMCs: peripheral blood mononuclear cells; ROC: receiver operating characteristic curve; SLE: systemic lupus erythematosus; SLEDAI, SLE disease activity index; Treg: regulatory T cells; WBCs: white blood cells.
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Lupus Eritematoso Sistémico , Monocitos , Humanos , Leucocitos Mononucleares , Complemento C4 , Anticuerpos Antinucleares , Receptores de Quimiocina , Lectinas Tipo CRESUMEN
There have been concerns raised about the environmental effects of perfluoroalkyl substances (PFASs) because of their toxicity, widespread distribution, and persistence. Understanding the occurrences and ecological risk posed by PFASs is essential, especially for the short-chain replacements perfluorobutanoic acid (PFBA) and perfluorobutane sulfonic acid (PFBS), which are now becoming predominant PFASs. The lack of aquatic life criteria (ALC), however, prevents an accurate assessment of the ecological risks of PFBA and PFBS. This study thus investigated the occurrence of 15 PFASs at 29 sampling sites in Shaying River Basin (in China) systematically, conducted the toxicity tests of PFBA and PFBS on eight resident aquatic organisms in China, and derived the predicted non-effect concentration (PNEC) values for PFBA and PFBS for two environmental media in China. The results showed that the total PFASs concentrations (ΣPFASs) ranged from 5.07 to 20.32 ng/L (average of 10.95 ng/L) in surface water, whereas in sediment, ΣPFASs ranged from 6.46 to 20.05 ng/g (dw) (average of 11.51 ng/g). The presence of PFBS was the most prominent PFASs in both water (0.372-8.194 ng/L) and sediment (4.54-15.72 ng/g), demonstrating that short-chain substitution effects can be observed in watersheds. The PNEC values for freshwater and sediment were 6.60 mg/L and 8.30 mg/kg (ww), respectively, for PFBA, and 14.04 mg/L, 37.08 mg/kg (ww), respectively, for PFBS. Ecological risk assessment of two long-chain PFASs, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), and two short-chain PFASs, PFBA and PFBS, using the hazard quotient method revealed that Shaying River and other major River Basins in China were at risk of PFOS contamination. This study contributes to a better understanding of the presence and risk of PFASs in the Shaying River and first proposes the ALCs for PFBA and PFBS in China, which could provide important reference information for water quality standards.
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Ácidos Alcanesulfónicos , Fluorocarburos , Contaminantes Químicos del Agua , Ríos , Monitoreo del Ambiente , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Exposición a Riesgos Ambientales , Ácidos Alcanesulfónicos/toxicidad , Ácidos Alcanesulfónicos/análisis , Fluorocarburos/toxicidad , Fluorocarburos/análisis , ChinaRESUMEN
ABC-stacked trilayer graphene on boron nitride (ABC-TLG/hBN) moiré superlattices provides a tunable platform for exploring Wigner crystal states in which the electron correlation can be controlled by electric and magnetic fields. Here we report the observation of magnetic field-stabilized Wigner crystal states in a ABC-TLG/hBN. We show that correlated insulating states emerge at multiple fractional and integer fillings corresponding to ν = 1/3, 2/3, 1, 4/3, 5/3, and 2 electrons per moiré lattice site under a magnetic field. These correlated insulating states can be attributed to generalized Mott states for the integer fillings and generalized Wigner crystal states for the fractional fillings. The generalized Wigner crystal states are stabilized by a vertical magnetic field and are strongest at one magnetic flux quantum per three moiré superlattices. The ν = 2 insulating state persists up to 30 T, which can be described by a Mott-Hofstadter transition at a high magnetic field.
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There are many kinds of agricultural pathogenic fungi, which may belong to pathogenic fungi in different species, such as Fusarium, Alternaria, Colletotrichum, Phytophthora, and other agricultural pathogens. Pathogenic fungi from different sources are widely distributed in agriculture, which threaten the lives of crops around the world and caused great damage to agricultural production and economic benefits. Due to the particularity of the marine environment, marine-derived fungi could produce natural compounds with unique structures, rich diversities, and significant bioactivities. Since marine natural products with different structural characteristics could inhibit different kinds of agricultural pathogenic fungi, secondary metabolites with antifungal activity could be used as lead compounds against agricultural pathogenic fungi. In order to summarize the structural characteristics of marine natural products against agricultural pathogenic fungi, this review systematically overview the activities against agricultural pathogenic fungi of 198 secondary metabolites from different marine fungal sources. A total of 92 references published from 1998 to 2022 were cited. KEY POINTS: ⢠Pathogenic fungi, which could cause damage to agriculture, were classified. ⢠Structurally diverse antifungal compounds from marine-derived fungi were summarized. ⢠The sources and distributions of these bioactive metabolites were analyzed.
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Productos Biológicos , Fusarium , Antifúngicos/farmacología , Antifúngicos/metabolismo , Productos Biológicos/metabolismo , Hongos/metabolismo , Alternaria/metabolismo , Fusarium/metabolismoRESUMEN
We describe the confining instabilities of a proposed quantum spin liquid underlying the pseudogap metal state of the hole-doped cuprates. The spin liquid can be described by a SU(2) gauge theory of Nf = 2 massless Dirac fermions carrying fundamental gauge charges-this is the low-energy theory of a mean-field state of fermionic spinons moving on the square lattice with π-flux per plaquette in the â¤2 center of SU(2). This theory has an emergent SO(5)f global symmetry and is presumed to confine at low energies to the Néel state. At nonzero doping (or smaller Hubbard repulsion U at half-filling), we argue that confinement occurs via the Higgs condensation of bosonic chargons carrying fundamental SU(2) gauge charges also moving in π â¤2-flux. At half-filling, the low-energy theory of the Higgs sector has Nb = 2 relativistic bosons with a possible emergent SO(5)b global symmetry describing rotations between a d-wave superconductor, period-2 charge stripes, and the time-reversal breaking "d-density wave" state. We propose a conformal SU(2) gauge theory with Nf = 2 fundamental fermions, Nb = 2 fundamental bosons, and a SO(5)f×SO(5)b global symmetry, which describes a deconfined quantum critical point between a confining state which breaks SO(5)f and a confining state which breaks SO(5)b. The pattern of symmetry breaking within both SO(5)s is determined by terms likely irrelevant at the critical point, which can be chosen to obtain a transition between Néel order and d-wave superconductivity. A similar theory applies at nonzero doping and large U, with longer-range couplings of the chargons leading to charge order with longer periods.
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Stilbenes (based on the 1,2-diphenylethylene skeleton) are a class of plant polyphenols with rich structural and bioactive diversity. Twenty-six stilbenes, including five undescribed compounds (7,8-dioxy-4,3',5'-trihydroxystilbene, trans-13'-methoxygnetin H, suffruticosol E, paestibenetrimerols A and B), were isolated from the seedcases of Paeonia suffruticosa Andrews. Their structures were elucidated by spectroscopic analyses and comparison with previously reported data. The absolute configurations of trans-13'-methoxygnetin H, suffruticosol E, paestibenetrimerols A and B were assigned from their respective electronic circular dichroism (ECD) spectra. Additionally, the structures of known compounds suffruticosols A, B and rockiol B were revised and the absolute configurations of them, and along with (+)-davidiol A, were also further determined by ECD. The isolated compounds, trans-gnetin H, cis-gnetin H and suffruticosol E, were found to have potent cytotoxicity against the DU-145 and MDA-MB-231 cell lines with IC50 values of 4.89-8.61 µM. The preliminary antitumor structure-activity relationship of these stilbenes is discussed as well.
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PaeoniaRESUMEN
A new withanolide, talasteroid (1), and a known steroid (2), along with eight meroterpenoids (3-10), were obtained from the rice culture of the marine-derived fungus Talaromyces stollii HBU-115. The structure of 1 including its absolute configuration was determined by extensive 1 D and 2 D NMR spectroscopy, and single-crystal X-ray diffraction analysis. Compound 1 represents the first withanolide featuring a 4-substituted 2,3-dimethyl-2-butenolide ring in the side chain. The isolated compounds were evaluated for their antimicrobial and antioxidant activities.
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BACKGROUND AND OBJECTIVE: esophageal cancer (EC) is one of the most common gastrointestinal malignant diseases. We conducted a comprehensive meta-analysis to explore the clinical applicability of circulating microRNA for the diagnosis of EC. METHODS: as of September 10, 2021, a comprehensive literature search was conducted on PubMed, Embase, Web of Science, Cochrane Library, Wanfang Database, and China National Knowledge Infrastructure (CNKI) to identify eligible studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were pooled to evaluate the test performance. The potential sources of heterogeneity were analyzed by subgroup analysis. Deeks' funnel plot was used to assess publication bias. RESULTS: 85 studies from 50 articles were included in the current meta-analysis. The overall pooled sensitivity was 0.82 (95 % CI, 0.79-0.84), specificity was 0.84 (95 % CI, 0.81-0.86), PLR was 4.9 (95 % CI, 4.2-5.9), NLR was 0.22 (95 % CI, 0.19-0.25), DOR was 22 (95 % CI, 17-29) and AUC was 0.89 (95 % CI, 0.86-0.92), respectively. Subgroup analysis suggested that miRNA clusters with a large sample size showed better diagnostic accuracy. Publication bias was not found. CONCLUSIONS: circulating miRNAs can be used as a potential non-invasive biomarker for the diagnosis of EC in Asian populations.
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MicroARN Circulante , Neoplasias Esofágicas , MicroARNs , Humanos , Sensibilidad y Especificidad , MicroARNs/genética , Biomarcadores , Neoplasias Esofágicas/diagnóstico , Biomarcadores de Tumor/genéticaRESUMEN
Three new polyketides, eutyketides A and B (1 and 2) and cytosporin X (3), along with four known compounds (4-7), were obtained from the marine-derived fungus Eutypella scoparia. The planar structures of 1 and 2 were elucidated by extensive HRMS and 1D and 2D NMR analyses. Their relative configurations of C-13 and C-14 were determined with chemical conversions by introducing an acetonylidene group. The absolute configurations of 1-3 were determined by comparing their experimental electronic circular dichroism (ECD) data with their computed ECD results. All of the isolated compounds were tested for their anti-inflammatory activities on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages. Compounds 5 and 6 showed stronger anti-inflammatory activities than the other compounds, with the inhibition of 49.0% and 54.9% at a concentration of 50.0 µg/mL, respectively.