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1.
Chem Biodivers ; : e202402071, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39318053

RESUMO

Four undescribed compounds including a pair of enantiomers of a dihydroarylnaphthalene lignan [(±)-1], an arylnaphthalene lignan (2), and an indoleacetic acid ester (3), together with four known compounds (4-7), were isolated from the seeds of Lepidium sativum. Their structures were identified by HRMS and NMR spectroscopic data, and the absolute configuration of these compounds were assigned by ECD data in combination with quantum chemical calculations. Compound (-)-1 had weak inhibitory activity against HeLa cell line with an IC50 value of 60.23 ± 3.51 µM, and compound (+)-1 presented moderate inhibitory effect against HeLa cell line with an IC50 value of 19.99 ± 1.00 µM (IC50 value of the positive control was 0.40 ±0.02 µM).

2.
Artigo em Inglês | MEDLINE | ID: mdl-39283192

RESUMO

In this study, we present an all-solid-state electrochromic device (ECD) that eliminates the need for hard-to-obtain materials and conventional liquid/gel electrolytes. Using a cost-effective and industrially scalable spray coating technique, we developed an ECD containing a layer of zinc oxide nanorods (ZnOnano) synthesized via a simple solochemical route. The device configuration includes a preformed Al-coated glass substrate, acting as a counter electrode, within a glass/Al/ZnOnano/PEDOT:PSS architecture. The device exhibits reversible switching between light blue and dark blue states upon application of -1.2 V and +2.8 V, respectively, with a significant difference in transmittance between bleached and colored states in the visible-NIR spectrum, featuring a high coloration efficiency of 275.62 cm2/C at 600 nm. The response times required for both coloring and bleaching states were 9.92 s and 7.51 s, respectively, for a sample with an active area of 5.5 × 2.5 cm2. Regarding the electrochemical stability of the ZnO-based ECD, the transmittance modulation reached around 8.01% at 600 nm after 12,800 s, following initial variations observed during the first 10 cycles. These results represent significant progress in electrochromic technology, offering a sustainable and efficient alternative to traditional ECDs. The use of economical fabrication techniques and the exclusion of critical materials highlight the potential for widespread industrial adoption of this novel ECD design.

3.
EJNMMI Res ; 14(1): 83, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39264384

RESUMO

BACKGROUND: Ictal brain perfusion SPECT provides higher sensitivity for the identification of the epileptic seizure onset zone (SOZ) than interictal SPECT. However, ictal SPECT is demanding due to the unpredictable waiting period for the next seizure to allow for ictal tracer injection. Thus, starting with an interictal scan and skipping the ictal scan if the interictal scan provides a SOZ candidate with high confidence could be an efficient approach. The current study estimated the rate of high-confidence SOZ candidates and the false lateralization rate among them for interictal and ictal SPECT. METHODS: 177 patients (48% females, median age 38y, interquartile range 27-48y) with ictal and interictal SPECT acquired with 99mTc-HMPAO (n = 141) or -ECD (n = 36) were included retrospectively. The vast majority of the patients was suspected to have temporal lobe epilepsy. Visual interpretation of the SPECT data was performed independently by 3 readers in 3 settings: "interictal only" (interictal SPECT and statistical hypoperfusion map), "ictal only" (ictal SPECT and hyperperfusion map), and "full" setting (side-by-side interpretation of ictal and interictal SPECT including statistical maps and SISCOM analysis). The readers lateralized the SOZ (right, left, none) and characterized their confidence using a 5-score. A case was considered "lateralizing with high confidence" if all readers lateralized to the same hemisphere with at least 4 of 5 confidence points. Lateralization of the SOZ in the "full" setting was used as reference standard. RESULTS: The proportion of "lateralizing with high confidence" cases was 4.5/31.6/38.4% in the "interictal only"/"ictal only"/"full" setting. One (12.5%) of the 8 cases that were "lateralizing with high confidence" in the "interictal only" setting lateralized to the wrong hemisphere. Among the 56 cases that were "lateralizing with high confidence" in the "ictal only" setting, 54 (96.4%) were also lateralizing in the "full" setting, all to the same hemisphere. CONCLUSIONS: Starting brain perfusion SPECT in the presurgical evaluation of epilepsy with an interictal scan to skip the ictal scan in case of a high-confidence interictal SOZ candidate is not a useful approach. In contrast, starting with an ictal scan to skip the interictal scan in case of a high-confidence ictal SOZ candidate can be recommended.

4.
Int J Mol Sci ; 25(17)2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39273606

RESUMO

Optically active heterodimeric 5,5'-linked bis-isochromans, containing a stereogenic ortho-trisubstituted biaryl axis and up to four chirality centers, were synthesized stereoselectively by using a Suzuki-Miyaura biaryl coupling reaction of optically active isochroman and 1-arylpropan-2-ol derivatives, providing the first access to synthetic biaryl-type isochroman dimers. Enantiomeric pairs and stereoisomers up to seven derivatives were prepared with four different substitution patterns, which enabled us to test how OR, ECD, and VCD measurements and DFT calculations can be used to determine parallel central and axial chirality elements in three isolated blocks of chirality. In contrast to natural penicisteckins A-D and related biaryls, the ECD spectra and OR data of (aS) and (aR) atropodiastereomers did not reflect the opposite axial chirality, but they were characteristic of the central chirality. The atropodiastereomers showed consistently near-mirror-image VCD curves, allowing the determination of axial chirality with the aid of DFT calculation or by comparison of characteristic VCD transitions.


Assuntos
Dimerização , Estereoisomerismo , Dicroísmo Circular , Estrutura Molecular , Cromanos/química , Cromanos/síntese química , Modelos Moleculares , Teoria da Densidade Funcional
5.
Biomed Pharmacother ; 179: 117338, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39278187

RESUMO

A recent study has introduced a recombinant fusion protein, consisting of the extracellular domain (ECD) of p75 and the Fc fragment of human immunoglobulin IgG1 (p75ECD-Fc), as a multifaceted agent within the nervous system. This research aimed to assess the effects of p75ECD-Fc on neuronal growth and the restoration of neurological functions in rats afflicted with neonatal hypoxic-ischemic encephalopathy (NHIE). In vitro analyses revealed that 1 µM p75ECD-Fc treatment markedly increased cell viability and facilitated neurite outgrowth in neurons exposed to oxygen-glucose deprivation (OGD). Subsequent in vivo studies determined that a dose of 78.6 µg/3 µl of p75ECD-Fc significantly mitigated brain damage and both acute and long-term neurological impairments, outperforming the therapeutic efficacy of hypothermia, as evidenced through behavioral assessments. Additionally, in vivo immunostaining showed that p75ECD-Fc administration enhanced neuronal survival and regeneration, and reduced astrocytosis and microglia activation in the cortex and hippocampus of NHIE rats. A noteworthy shift from A1 to A2 astrocyte phenotypes and from M1 to M2 microglia phenotypes was observed after p75ECD-Fc treatment. Furthermore, a co-expression of the p75 neurotrophin receptor (p75NTR) and Nestin was identified, with an overexpression of Nestin alleviating the neurological dysfunction induced by NHIE. Mechanistically, the neuroprotective effects of p75ECD-Fc, particularly its inhibition of neuronal apoptosis post-OGD, may be attributed to Nestin. Taken together, these results highlight the neuroprotective and anti-inflammatory effects of p75ECD-Fc treatment through the modulation of glial cell phenotypes and the Nestin-mediated inhibition of neuronal apoptosis, positioning it as a viable therapeutic approach for NHIE.


Assuntos
Animais Recém-Nascidos , Apoptose , Hipóxia-Isquemia Encefálica , Fragmentos Fc das Imunoglobulinas , Nestina , Ratos Sprague-Dawley , Animais , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Hipóxia-Isquemia Encefálica/patologia , Hipóxia-Isquemia Encefálica/metabolismo , Apoptose/efeitos dos fármacos , Nestina/metabolismo , Fragmentos Fc das Imunoglobulinas/farmacologia , Ratos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Proteínas Recombinantes de Fusão/farmacologia , Masculino , Sobrevivência Celular/efeitos dos fármacos , Microglia/efeitos dos fármacos , Microglia/patologia , Microglia/metabolismo , Humanos , Receptores de Fator de Crescimento Neural/metabolismo , Modelos Animais de Doenças
6.
Phytochemistry ; 229: 114281, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39265878

RESUMO

Five previously undescribed compounds, including three 12-nor-rotenoids, were isolated from Pachyrhizus erosus seeds. A brief survey on the dealkylation of selected rotenoids with BBr3 was undertaken. Spectroscopic data of these previously undescribed compounds and reaction products are reported. The proposal of absolute configurations at stereocenters in the isolates and reaction products was based on NMR and ECD data. Most of the isolates and reaction products were evaluated for their growth inhibitory activities against four cancer cell lines and a Vero cell line. Many compounds exhibited strong to moderate activities with IC50 values ranging from 0.06 to 20.9 µM, and their structure-activity relationships were evaluated.

8.
BMC Ophthalmol ; 24(1): 344, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143510

RESUMO

BACKGROUND: To investigate the safety and effectiveness of non-viscoelastic agent technique for EVO-ICL implantation. METHODS: A total of 181 myopia eyes that underwent non-toric ICL without viscoelastic agent through single incision from Beijing Tongren Hosipital were included. An analysis was conducted on the quantity of haptics that were initially implanted intraoperatively into the posterior chamber. Intraocular pressure (IOP) was evaluated at before and 2 h,24 h,1week,6month after surgery. Anterior chamber volume(ACV), anterior chamber depth(ACD), anterior chamber angle(ACA), pupil diameter(PD) and corneal densitometry density (ECD) were evaluated at before and 24 h postoperatively. Refractive outcomes were investigated at before, 24 h ,7 days and 6months. Vault was evaluated at 24 h ,7 days and 6months. RESULTS: The efficacy and safety indices were 1.30 ± 0.32 and 1.31 ± 0.32, respectively. Of 181 eyes, 99 eyes received 4 haptics on the first attempt without any adjustment, and 72 eyes received lens alignment without an viscoelastic agent. The success rate of the viscoelastic agent free procedure was 94.5%. Two hours postoperatively, IOP was 17.41 ± 3.77 mmHg, which was significantly higher than baseline value (t = 8.930, P < 0.000), however there was no significant difference between preoperative IOP and IOP at 1 day ,1 week and 6 months postoperatively. The ECD changed from 2895.52 ± 253.73 cells/mm2 preoperatively to 2873.66 ± 244.17 cells/mm2 at 1 day and 2882.63 ± 239.97 postoperatively, and the difference was not statistically significant (t = 1.811, P = 0.072). The ACA was narrowed by 42% on the first day. CONCLUSION: The pure viscoelastic agent free technique is an efficient and safe way for ICL implantation. It can be a safer method of ICL implantation because of it reduces the risk of complications associated with ocular hypertension at the early postoperative stages. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2000036335) at August 20, 2020.


Assuntos
Pressão Intraocular , Implante de Lente Intraocular , Miopia , Acuidade Visual , Humanos , Feminino , Masculino , Adulto , Implante de Lente Intraocular/métodos , Pressão Intraocular/fisiologia , Adulto Jovem , Miopia/cirurgia , Miopia/fisiopatologia , Refração Ocular/fisiologia , Pessoa de Meia-Idade , Substâncias Viscoelásticas/administração & dosagem , Adolescente , Lentes Intraoculares , Estudos Prospectivos , Seguimentos , Resultado do Tratamento
9.
Front Transplant ; 3: 1449407, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39176402

RESUMO

Since the first liver transplant was performed over six decades ago, the landscape of liver transplantation in the US has seen dramatic evolution. Numerous advancements in perioperative and operative techniques have resulted in major improvements in graft and patient survival rates. Despite the increase in transplants performed over the years, the waitlist mortality rate continues to remain high. The obesity epidemic and the resultant metabolic sequelae continue to result in more marginal donors and challenging recipients. In this review, we aim to highlight the changing characteristics of liver transplant recipients and liver allograft donors. We focus on issues relevant in successfully transplanting a high model for end stage liver disease recipient. We provide insights into the current use of terms and definitions utilized to discuss marginal allografts, discuss the need to look into more consistent ways to describe these organs and propose two new concepts we coin as "Liver Allograft Variables" (LAV) and "Liver Allograft Composite Score" (LACS) for this. We discuss the development of spectrum of risk indexes as a dynamic tool to characterize an allograft in real time. We believe that this concept has the potential to optimize the way we allocate, utilize and transplant livers across the US.

10.
Trials ; 25(1): 556, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39180108

RESUMO

BACKGROUND: Vulnerable children, including those with neuro-developmental delays and disabilities, often face barriers in accessing early primary education, thus hindering progress toward Sustainable Development Goal 4.2. Evidence-based interventions are essential to enhancing inclusivity and establishing sustainable implementation strategies to address this challenge. This study, Every Newborn-Reach up Early Education Intervention for All Children (EN-REACH), builds on the previous Every Newborn- Simplified Measurement Integrating Longitudinal Neurodevelopmental and Growth (EN-SMILING) observational cohort study. This paper provides the protocol for a cluster randomized controlled trial (cRCT) to evaluate the effectiveness of a parenting group intervention program for enhancing school readiness in Bangladesh, Nepal, and Tanzania, and an embedded process evaluation to inform scalability and feasibility. METHODS: EN-REACH is a cRCT with at least 150 clusters to evaluate the impact of a parent training program led by trained parent-teacher facilitator pairs, focusing on children aged 4 ~ 6 years preparing for preschool. Approximately 500 participants from the EN-SMILING cohort at each site have been identified. A geographic information system will define ~ 50 clusters in each of the three countries, each with approximately ten parent-child dyads. Half the clusters will be randomly assigned to intervention and control groups. The primary outcome is "school readiness", assessed using the Measuring Early Learning Quality and Outcomes tool. Secondary outcomes include Intelligence Quotient, child functioning, growth, visual, and hearing assessments. Data will be collected at baseline, and post-intervention data following implementation of the parent group intervention sessions over approximately 5 months. Quantitative data on coverage and quality care, combined with qualitative insights from children, caregivers, facilitators, and stakeholders' perspectives, will be used to conduct a process evaluation applying the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework.  DISCUSSION: This protocol details a trial focused on enhancing school readiness and cognitive abilities in young children, inclusive of those with disabilities, aiming to bridge gap from home to early primary education. EN-REACH aims to provide insights into the effectiveness and acceptability of a co-designed disability-inclusive school readiness program in three countries, potentially impacting national and global policies for all children, including those with disabilities. TRIAL REGISTRATION: The trial was retrospectively registered on clinicaltrials.gov on 29 February 2024 (NCT06334627).


Assuntos
Desenvolvimento Infantil , Intervenção Educacional Precoce , Pais , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Tanzânia , Pré-Escolar , Nepal , Intervenção Educacional Precoce/métodos , Bangladesh , Pais/educação , Pais/psicologia , Criança , Feminino , Masculino , Estudos Multicêntricos como Assunto , Fatores de Tempo , Poder Familiar , Comportamento Infantil , Recém-Nascido , Fatores Etários , Capacitação de Professores/métodos
11.
J Alzheimers Dis ; 100(4): 1299-1314, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39031358

RESUMO

Background: Cerebral autosomal-dominant arteriopathy with subcortical infarction and leukoencephalopathy (CADASIL) is an inherited small-vessel disease that affects the white matter of the brain. Recent studies have confirmed that the deposition of NOTCH3ECD is the main pathological basis of CADASIL; however, whether different mutations present the same pathological characteristics remains to be further studied. Some studies have found that mitochondrial dysfunction is related to CADASIL; however, the specific effects of NOTCH3ECD on mitochondrial remain to be determined. Objective: We aimed to explore the role of mitochondrial dysfunction in CADASIL. Methods: We established transgenic human embryonic kidney-293T cell models (involving alterations in cysteine and non-cysteine residues) via lentiviral transfection. Mitochondrial function and structure were assessed using flow cytometry and transmission electron microscopy, respectively. Mitophagy was assessed using western blotting and immunofluorescence. Results: We demonstrated that NOTCH3ECD deposition affects mitochondrial morphology and function, and that its protein levels are significantly correlated with mitochondrial quality and can directly bind to mitochondria. Moreover, NOTCH3ECD deposition promoted the induction of autophagy and mitophagy. However, these processes were impaired, leading to abnormal mitochondrial accumulation. Conclusions: This study revealed a common pathological feature of NOTCH3ECD deposition caused by different NOTCH3 mutations and provided new insights into the role of NOTCH3ECD in mitochondrial dysfunction and mitophagy.


Assuntos
CADASIL , Mitocôndrias , Mitofagia , Receptor Notch3 , Humanos , CADASIL/genética , CADASIL/patologia , CADASIL/metabolismo , Receptor Notch3/genética , Receptor Notch3/metabolismo , Mitofagia/fisiologia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mitocôndrias/ultraestrutura , Células HEK293 , Mutação , Autofagia/fisiologia
12.
Mol Cell Proteomics ; 23(9): 100814, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39029587

RESUMO

Protein tandem mass spectrometry (MS/MS) often generates sequence-informative fragments from backbone bond cleavages near the termini. This lack of fragmentation in the protein interior is particularly apparent in native top-down mass spectrometry (MS). Improved sequence coverage, critical for reliable annotation of posttranslational modifications and sequence variants, may be obtained from internal fragments generated by multiple backbone cleavage events. However, internal fragment assignments can be error prone due to isomeric/isobaric fragments from different parts of a protein sequence. Also, internal fragment generation propensity depends on the chosen MS/MS activation strategy. Here, we examine internal fragment formation in electron capture dissociation (ECD) and electron transfer dissociation (ETD) following native and denaturing MS, as well as LC/MS of several proteins. Experiments were undertaken on multiple instruments, including quadrupole time-of-flight, Orbitrap, and high-field Fourier-transform ion cyclotron resonance (FT-ICR) across four laboratories. ECD was performed at both ultrahigh vacuum and at similar pressure to ETD conditions. Two complementary software packages were used for data analysis. When feasible, ETD-higher energy collision dissociation MS3 was performed to validate/refute potential internal fragment assignments, including differentiating MS3 fragmentation behavior of radical versus even-electron primary fragments. We show that, under typical operating conditions, internal fragments cannot be confidently assigned in ECD or ETD. On the other hand, such fragments, along with some b-type terminal fragments (not typically observed in ECD/ETD spectra) appear at atypical ECD operating conditions, suggesting they originate from a separate ion-electron activation process. Furthermore, atypical fragment ion types, e.g., x ions, are observed at such conditions as well as upon EThcD, presumably due to vibrational activation of radical z-type ions.

13.
Chirality ; 36(7): e23696, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38965734

RESUMO

Through molecular recognition, drugs can interact and complex with macromolecules circulating in the body. The serum albumin transport protein, found in several mammals, has several interaction sites where these molecules can be located. The drug sulfasalazine (SSZ) is known in the literature to complex at drug site 1 (DS1) in human serum (HSA) and bovine serum (BSA) proteins. This complexation can be studied using various spectroscopic techniques. With the techniques used in this work, absorption in the ultraviolet and visible regions (UV-Vis) and electronic circular dichroism (ECD), a significant difference was observed in the results involving HSA and BSA. The application of theoretical methodologies, such as TD-DFT and molecular docking, suggests that the conformation that SSZ assumes in DS1 of the two proteins is different, which exposes it to different amino acid residues and different hydrophobicities. This difference in conformation may be related to the location of DS1 where the drug interacts or to the possibility of SSZ moving in the BSA site, due to its larger size, and moving less freely in HSA.


Assuntos
Simulação de Acoplamento Molecular , Soroalbumina Bovina , Sulfassalazina , Sulfassalazina/química , Soroalbumina Bovina/química , Humanos , Bovinos , Animais , Estereoisomerismo , Dicroísmo Circular , Albumina Sérica Humana/química , Teoria da Densidade Funcional
14.
Asia Ocean J Nucl Med Biol ; 12(2): 120-130, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39050240

RESUMO

Objectives: A simple noninvasive microsphere (SIMS) method using 123I-IMP and an improved brain uptake ratio (IBUR) method using 99mTc-ECD for the quantitative measurement of regional cerebral blood flow have been recently reported. The input functions of these methods were determined using the administered dose, which was obtained by analyzing the time activity curve of the pulmonary artery (PA) for SIMS and the ascending aorta (AAo) for the IBUR methods for dynamic chest images. If the PA and AAo regions of interest (ROIs) can be determined using deep convolutional neural networks (DCNN) for segmentation, the accuracy of these ROI-setting methods can be improved through simple analytical operations to ensure repeatability and reproducibility. The purpose of this study was to develop new PA and AAo-ROI setting methods using a DCNN (DCNN-ROI method). Methods: A U-Net architecture based on convolutional neural networks was used to determine the PA and AAo candidate regions. Images of 290 patients who underwent 123I-IMP RI-angiography and 108 patients who underwent 99mTc-ECD RI-angiography were used. The PA and AAo-ROI results for the DCNN-ROI method were compared to those obtained using manual methods. The counts for the input function on the PA and AAo-ROI were determined by integrating the area under the curve (AUC) counts of the time-activity curve of PA and AAo-ROI, respectively. The effectiveness of the DCNN-ROI method was elucidated through a comparison with the integrated AUC counts of the DCNN-ROI and the manual ROI. Results: The coincidence ratio for the locations of the PA and AAo-ROI obtained using the DCNN method and that for the manual method was 100%. Strong correlations were observed between the AUC counts using the DCNN and manual methods. Conclusion: New ROI- setting programs were developed using a deep convolution neural network DCNN to determine the input functions for the SIMS and IBUR methods. The accuracy of these methods is comparable to that of the manual method.

15.
Heliyon ; 10(12): e33289, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39022069

RESUMO

Dichlorodiphenyltrichloroethane is an organo-chlorine insecticide used for malaria and agricultural pest control, but it is the most persistent pollutant, endangering both human and environmental health. The primary aim of the research is to screen, characterize, and assess putative fungi that degrade DDT for mycoremediation. Samples of soil and wastewater were gathered from Addis Ababa, Koka, and Ziway. Fungi were isolated and purified using potato dextrose media. Matrix-Assisted Laser Desorption, Ionization, and Flight Duration The technique of mass spectrometry was employed to identify fungi. It was found that the finally selected isolate, AS1, was Aspergillus niger. Based on growth factor optimization at DDT concentrations (0, 3500, and 7000 ppm), temperatures (25, 30, and 35 °C), and pH levels (4, 7, and 10), the potential DDT-tolerant fungal isolates were investigated. A Box-Behnken experimental design was used to analyze and optimize fungal biomass and sporulation. The highest biomass (0.981 ± 0.22 g) and spore count (5.60 ± 0.32 log/mL) of A. niger were found through optimization assessment, and this fungus was chosen as a potential DDT-degrader. For DDT degradation investigations by A. niger in DDT-amended liquid media, gas chromatograph-electron capture detector technology was employed. DDT and its main metabolites, DDE and DDD, were eliminated from both media to the tune of 96-99 % at initial DDT concentrations of 1750, 3500, 5250, and 7000 ppm. In conclusion, it is a promising candidate for detoxifying and/or removing DDT and its breakdown products from contaminated environments.

16.
J Agric Food Chem ; 72(29): 16298-16311, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38982710

RESUMO

From the fruits of Cordia dichotoma, 11 new phenolic compounds, dichotomins A-K, were isolated, together with 19 known compounds. Through the analysis of detailed NMR data and HRESIMS data, the planar structures of all compounds were confirmed. Using NMR calculations, the absolute configuration of dichotomins A-K was elucidated by comparing their observed and computed electronic circular dichroism (ECD) spectra. Dichotomin H (8) and dichotomin I (9) were determined as two pairs of enantiomers. The enantiomers of compounds 8 and 9 were separated using chiral-phase high-performance liquid chromatography (HPLC), and the stereostructure of each enantiomer was determined by similarly calculating the ECD. Compounds 3, 5, 7, 17, 18, 23-25, and 27-30 increased glucose uptake by 1.04- to 2.85-folds at concentrations of 30 µg/mL. Further studies revealed that compounds 3 and 5 had a moderate effect on glucose transporter 4 (GLUT4) translocation activity in L6 cells. At 30 µg/mL, compound 3 significantly enhanced AMPK phosphorylation and GLUT4 expression. As a whole, compound 3 has the potential to be a drug candidate for the treatment of type 2 diabetes mellitus (T2DM).


Assuntos
Frutas , Transportador de Glucose Tipo 4 , Glucose , Fenóis , Extratos Vegetais , Transportador de Glucose Tipo 4/metabolismo , Transportador de Glucose Tipo 4/genética , Frutas/química , Glucose/metabolismo , Fenóis/química , Fenóis/farmacologia , Fenóis/metabolismo , Animais , Ratos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/metabolismo , Transporte Biológico/efeitos dos fármacos , Estrutura Molecular , Linhagem Celular , Transporte Proteico , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/química
17.
Mar Drugs ; 22(7)2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39057426

RESUMO

Ten new decalin polyketides, zosteropenilline M (1), 11-epi-8-hydroxyzosteropenilline M (2), zosteropenilline N (3), 8-hydroxyzosteropenilline G (4), zosteropenilline O (5), zosteropenilline P (6), zosteropenilline Q (7), 13-dehydroxypallidopenilline A (8), zosteropenilline R (9) and zosteropenilline S (10), together with known zosteropenillines G (11) and J (12), pallidopenilline A (13) and 1-acetylpallidopenilline A (14), were isolated from the ethyl acetate extract of the fungus Penicillium yezoense KMM 4679 associated with the seagrass Zostera marina. The structures of isolated compounds were established based on spectroscopic methods. The absolute configurations of zosteropenilline Q (7) and zosteropenilline S (10) were determined using a combination of the modified Mosher's method and ROESY data. The absolute configurations of zosteropenilline M (1) and zosteropenilline N (3) were determined using time-dependent density functional theory (TD-DFT) calculations of the ECD spectra. A biogenetic pathway for compounds 1-14 is proposed. The antimicrobial, cytotoxic and cytoprotective activities of the isolated compounds were also studied. The significant cytoprotective effects of the new zosteropenilline M and zosteropenillines O and R were found in a cobalt chloride (II) mimic in in vitro hypoxia in HEK-293 cells. 1-Acetylpallidopenilline A (14) exhibited high inhibition of human breast cancer MCF-7 cell colony formation with IC50 of 0.66 µM and its anticancer effect was reduced when MCF-7 cells were pretreated with 4-hydroxitamoxifen. Thus, we propose 1-acetylpallidopenilline A as a new xenoestrogen with significant activity against breast cancer.


Assuntos
Penicillium , Zosteraceae , Penicillium/química , Humanos , Linhagem Celular Tumoral , Policetídeos/farmacologia , Policetídeos/química , Policetídeos/isolamento & purificação , Células MCF-7 , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Organismos Aquáticos
18.
Nat Prod Res ; : 1-7, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38988300

RESUMO

A new pair of butylphthalide diastereomers, dangguinolide A (1) and dangguinolide B (2), together with two known butylphthalide were isolated from Angelica sinensis. Their structures were determined by extensive spectroscopic analyses, and the absolute configurations of 1 and 2 were assigned via NMR calculations and ECD calculations. Their anti-inflammatory activities have evaluated in vitro.

19.
Front Public Health ; 12: 1409215, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38975354

RESUMO

Endocrine disruptors (ED) are ubiquitous pollutants, possibly implicated in chronic disease. Exposure of vulnerable populations; including neonates, infants and children; must therefore be limited. Informing parents is now a public health challenge. We conducted a quantitative cross-sectional study at the Lyon Mother and child Hospital. We used questionnaires to assess the beliefs and knowledge about ED of parents and pediatric healthcare professionals in the pediatric ward in Lyon, France. A total of 746 questionnaires were completed: 444 for professionals and 302 for parents. The majority of both populations had already heard of ED but only 10% of parents and 5% of professionals felt sufficiently informed. Professionals answered better than parents (73% vs. 60%). The main source of information was similar: media. Only 20% of professionals had read a scientific article about ED and 4% have followed a training. Environmental exposure and EDs is an increasing concern for parents but specific knowledge remains scare for parents and professionals. Specific training is needed.


Assuntos
Disruptores Endócrinos , Conhecimentos, Atitudes e Prática em Saúde , Pais , Humanos , Estudos Transversais , Feminino , Inquéritos e Questionários , Masculino , Pais/psicologia , França , Adulto , Exposição Ambiental , Criança , Pediatria , Lactente
20.
Chem Biodivers ; 21(8): e202400946, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38869958

RESUMO

A new monoterpene, (-)-10-hydroxydihydroactinidiolide (1), along with two known monoterpenes, loliolide (2) and (+)-isololiolide (3), three known megastigmanes, 3α-hydroxy-5ß,6ß-epoxy-ß-ionone (4), 3α-hydroxy-5α,6α-epoxy-ß-ionone (5), and (+)-dehydrovomifoliol (6), a eudesmane-type sesquiterpene, 4α-hydroxy-4ß-methyldihydrocostol (7), a monoterpene, 8-hydroxycarvotanacetone (8), two flavonoids, chrysoeriol (9) and apigenin (10), and a phenylpropanoid, 3-(4-hydroxyphenyl)-1-propanol (11), were isolated from the whole plant of Achillea millefolium. The structure of compound 1 was identified according to spectroscopic data of HRMS and NMR, and its absolute configuration was assigned by 13C NMR calculations with DP4+ probability analyses and ECD calculations. The absolute configuration of compound 6 was determined by ECD calculations. Compounds 3, 6, 9 and 10 could dose-dependently inhibit the NO release in LPS-induced RAW264.7 cells.


Assuntos
Achillea , Anti-Inflamatórios , Achillea/química , Camundongos , Animais , Células RAW 264.7 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga
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