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1.
Genes Dev ; 36(3-4): 133-148, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35086862

RESUMO

The regeneration of peripheral nerves is guided by regeneration tracks formed through an interplay of many cell types, but the underlying signaling pathways remain unclear. Here, we demonstrate that macrophages are mobilized ahead of Schwann cells in the nerve bridge after transection injury to participate in building regeneration tracks. This requires the function of guidance receptor Plexin-B2, which is robustly up-regulated in infiltrating macrophages in injured nerves. Conditional deletion of Plexin-B2 in myeloid lineage resulted in not only macrophage misalignment but also matrix disarray and Schwann cell disorganization, leading to misguided axons and delayed functional recovery. Plexin-B2 is not required for macrophage recruitment or activation but enables macrophages to steer clear of colliding axons, in particular the growth cones at the tip of regenerating axons, leading to parallel alignment postcollision. Together, our studies unveil a novel reparative function of macrophages and the importance of Plexin-B2-mediated collision-dependent contact avoidance between macrophages and regenerating axons in forming regeneration tracks during peripheral nerve regeneration.


Assuntos
Regeneração Nervosa , Nervos Periféricos , Axônios/fisiologia , Moléculas de Adesão Celular , Macrófagos/metabolismo , Regeneração Nervosa/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Nervos Periféricos/metabolismo , Células de Schwann/metabolismo
2.
Plant J ; 118(3): 802-822, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38305492

RESUMO

Floral patterns are unique to rice and contribute significantly to its reproductive success. SL1 encodes a C2H2 transcription factor that plays a critical role in flower development in rice, but the molecular mechanism regulated by it remains poorly understood. Here, we describe interactions of the SL1 with floral homeotic genes, SPW1, and DL in specifying floral organ identities and floral meristem fate. First, the sl1 spw1 double mutant exhibited a stamen-to-pistil transition similar to that of sl1, spw1, suggesting that SL1 and SPW1 may located in the same pathway regulating stamen development. Expression analysis revealed that SL1 is located upstream of SPW1 to maintain its high level of expression and that SPW1, in turn, activates the B-class genes OsMADS2 and OsMADS4 to suppress DL expression indirectly. Secondly, sl1 dl displayed a severe loss of floral meristem determinacy and produced amorphous tissues in the third/fourth whorl. Expression analysis revealed that the meristem identity gene OSH1 was ectopically expressed in sl1 dl in the fourth whorl, suggesting that SL1 and DL synergistically terminate the floral meristem fate. Another meristem identity gene, FON1, was significantly decreased in expression in sl1 background mutants, suggesting that SL1 may directly activate its expression to regulate floral meristem fate. Finally, molecular evidence supported the direct genomic binding of SL1 to SPW1 and FON1 and the subsequent activation of their expression. In conclusion, we present a model to illustrate the roles of SL1, SPW1, and DL in floral organ specification and regulation of floral meristem fate in rice.


Assuntos
Flores , Regulação da Expressão Gênica de Plantas , Meristema , Oryza , Proteínas de Plantas , Oryza/genética , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Meristema/genética , Meristema/crescimento & desenvolvimento , Meristema/metabolismo , Flores/genética , Flores/crescimento & desenvolvimento , Flores/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Plantas Geneticamente Modificadas , Mutação
3.
Cell Commun Signal ; 22(1): 117, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347600

RESUMO

Post-translational modifications (PTMs) of the non-histone protein high-mobility group protein B1 (HMGB1) are involved in modulating inflammation and immune responses. Recent studies have implicated that the RNA-binding protein (RBP) Musashi-2 (MSI2) regulates multiple critical biological metabolic and immunoregulatory functions. However, the precise role of MSI2 in regulating PTMs and tumor immunity in colorectal cancer (CRC) remains unclear. Here, we present data indicating that MSI2 potentiates CRC immunopathology in colitis-associated colon cancer (CAC) mouse models, cell lines and clinical specimens, specifically via HMGB1-mediated dendritic cell (DC) maturation and migration, further contributes to the infiltration of CD4+ and CD8+ T cells and inflammatory responses. Under stress conditions, MSI2 can exacerbate the production, nucleocytoplasmic transport and extracellular release of damage-associated molecular patterns (DAMPs)-HMGB1 in CRC cells. Mechanistically, MSI2 mainly enhances the disulfide HMGB1 production and protein translation via direct binding to nucleotides 1403-1409 in the HMGB1 3' UTR, and interacts with the cytoplasmic acetyltransferase P300 to upregulate its expression, further promoting the acetylation of K29 residue in HMGB1, thus leading to K29-HMGB1 nucleocytoplasmic translocation and extracellular release. Furthermore, blocking HMGB1 activity with glycyrrhizic acid (Gly) attenuates MSI2-mediated immunopathology and immune infiltration in CRC in vitro and in vivo. Collectively, this study suggests that MSI2 may improve the prognosis of CRC patients by reprogramming the tumor immune microenvironment (TIME) through HMGB1-mediated PTMs, which might be a novel therapeutic option for CRC immunotherapy.


Assuntos
Neoplasias Colorretais , Proteína HMGB1 , Animais , Humanos , Camundongos , Linfócitos T CD8-Positivos , Neoplasias Colorretais/metabolismo , Citosol/metabolismo , Proteína HMGB1/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas de Ligação a RNA/genética , Microambiente Tumoral
4.
J Genet Couns ; 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38217320

RESUMO

Increased utilization of genomic sequencing in pediatric medicine has increased the detection of variants of uncertain significance (VUS). Periodic VUS reinterpretation can clarify clinical significance and increase diagnostic yield, highlighting the importance of systematic VUS tracking and reinterpretation. There are currently no standardized guidelines or established best practices for VUS management, and our understanding of how genetic counselors (GCs) track and manage VUS results for pediatric patients is limited. In this exploratory study, GCs in pediatric clinics in North America were surveyed about their VUS management practices. A total of 124 responses were included in the analysis. The majority (n = 115, 92.7%) of GCs reported that VUS management workflows were at the discretion of each individual provider in their workplace. Approximately half (n = 65, 52%) kept track of patient VUS results over time, and GCs with lower patient volumes were more likely to do so (p = 0.04). While 95% (n = 114) of GCs had requested VUS reinterpretation at least once, only 5% (n = 6) requested it routinely. Most (n = 80, 86%) GCs notified patients when a VUS was reclassified, although methods of recontact differed when the reclassification was an upgrade versus a downgrade. GCs who asked patients to stay in touch through periodic recontact or follow-up appointments were more likely to request VUS reinterpretation (p = 0.01). The most frequently reported barriers to requesting reinterpretation regularly were patients being lost to follow-up (n = 39, 33.1%), insufficient bandwidth (n = 27, 22.9%), and lack of standardized guidelines (n = 25, 21.2%). GCs had consistent overall practices around VUS management around investigation, disclosure, reinterpretation, and recontact, but specific methods used differed and were at the discretion of each provider. These results showcase the current landscape of VUS management workflows in pediatrics and the challenges associated with adopting more uniform practices. The study findings can help inform future strategies to develop standardized guidelines surrounding VUS management.

5.
J Asian Nat Prod Res ; 26(4): 452-464, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37655543

RESUMO

Six previously undescribed prenylated C6-C3 derivatives (1-6) were isolated from the root of Illicium ternstroemioides A. C. Smith. Their structures were elucidated based on extensive spectroscopic analyses (UV, IR, 1D and 2D NMR, and HRESIMS). The absolute configurations of 1-3 were determined using electronic circular dichroism (ECD), and Mo2(OAc)4 induced circular dichroism (ICD). Compound 3 exhibited weak activity against Coxsackievirus B3 with an IC50 value of 33.3 µM, and compound 5 exhibited more potent activity against Coxsackievirus B3 with an IC50 value of 6.4 µM.


Assuntos
Illicium , Illicium/química , Estrutura Molecular , Espectroscopia de Ressonância Magnética , Dicroísmo Circular , Antivirais/farmacologia
6.
J Asian Nat Prod Res ; : 1-13, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38885306

RESUMO

Three new prenylated C6-C3 compounds (1-3), together with two known prenylated C6-C3 compounds (4-5) and one known C6-C3 derivative (6), were isolated from the roots of Illicium brevistylum A. C. Smith. The structures of 1-3 were elucidated by spectroscopic methods including 1D and 2D NMR, HRESIMS, CD experiments and ECD calculations. The structure of illibrefunone A (1) was confirmed by single-crystal X-ray diffraction analysis. All compounds were evaluated in terms of their anti-inflammatory potential on nitric oxide (NO) generation in lipopolysaccharide-stimulated murine RAW264.7 macrophages and murine BV2 microglial cells, antiviral activity against Coxsackievirus B3 (CVB3) and influenza virus A/Hanfang/359/95 (H3N2). Compounds 3 and 4 exhibited potent inhibitory effects on the production of NO in RAW 264.7 cells with IC50 values of 20.57 and 12.87 µM respectively, which were greater than those of dexamethasone (positive control). Compounds 1 and 4-6 exhibited weak activity against Coxsackievirus B3, with IC50 values ranging from 25.87 to 33.33 µM.

7.
J Asian Nat Prod Res ; 26(2): 204-213, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38213077

RESUMO

Three new cadinane sesquiterpenes (1-3) and three known sesquiterpenes were isolated from the stems and branches of Illicium ternstroemioides A. C. Smith. The structures of the new compounds were elucidated by extensive analysis of spectroscopic and HRESIMS data. The structures of illiternins A-C (1-3) were confirmed by single crystal X-ray diffraction, allowing for the determination of their absolute configurations. Compounds 3 and 6 exhibited antiviral activity against Coxsackievirus B3 with IC50 values of 33.3 and 57.7 µM, respectively.


Assuntos
Illicium , Sesquiterpenos , Illicium/química , Estrutura Molecular , Sesquiterpenos Policíclicos , Sesquiterpenos/química
8.
Molecules ; 29(3)2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38338364

RESUMO

To develop a cost-effective method for the effective removal of reactive brilliant blue KN-R (RBB KN-R) from wastewater, we investigated the interactions between RBB KN-R and three cationic surfactants with different alkyl chain lengths, namely dodecyltrimethylammonium bromide (DTAB), tetradecyltrimethylammonium bromide (TTAB), and cetyltrimethylammonium bromide (CTAB). Employing a conductivity analysis, surface tension analysis, ultraviolet-visible spectrophotometry, and molecular dynamics simulation, we ascertained that RBB KN-R formed a 1:1 molar ratio dye-surfactant complex with each surfactant through electrostatic attraction. Notably, an augmentation in alkyl chain length correlated with increased binding strength between RBB KN-R and the surfactant. The resulting dye-surfactant complex exhibited heightened surface activity, enabling interactions through hydrophobic forces to generate dye-surfactant aggregates when the molar ratio was below 1:1. Within these mixed aggregates, self-assembly of RBB KN-R molecules occurred, leading to the formation of dye aggregates. Due to the improved hydrophobicity with increased alkyl chain length, TTAB and CTAB could encapsulate dye aggregates within the mixed aggregates, but DTAB could not. The RBB KN-R aggregates tended to distribute on the surface of the RBB KN-R-DTAB mixed aggregates, resulting in low stability. Thus, at a DTAB concentration lower than CMC, insoluble particles readily formed and separated from surfactant aggregates at an RBB KN-R and DTAB molar ratio of 1:4. Analyzing the RBB KN-R precipitate through scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) and measuring the DTAB concentration in the supernate revealed that, at this molar ratio, all RBB KN-R precipitated from the dye-surfactant mixed solution, with only 7.5 ± 0.5% of DTAB present in the precipitate. Furthermore, the removal ratio of RBB KN-R reached nearly 100% within a pH range of 1.0 to 9.0 and standing time of 6 h. The salt type and concentration did not significantly affect the precipitation process. Therefore, this simultaneous achievement of successful RBB KN-R removal and effective separation from DTAB underscores the efficacy of the proposed approach.

9.
Angew Chem Int Ed Engl ; 63(9): e202309958, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-37943171

RESUMO

Therapeutic peptides are a major class of pharmaceutical drugs owing to their target-binding specificity as well as their versatility in inhibiting aberrant protein-protein interactions associated with human pathologies. Within the realm of amyloid diseases, the use of peptides and peptidomimetics tailor-designed to overcome amyloidogenesis has been an active research endeavor since the late 90s. In more recent years, incorporating nanoparticles for enhancing the biocirculation and delivery of peptide drugs has emerged as a frontier in nanomedicine, and nanoparticles have further demonstrated a potency against amyloid aggregation and cellular inflammation to rival strategies employing small molecules, peptides, and antibodies. Despite these efforts, however, a fundamental understanding of the chemistry, characteristics and function of peptido-nanocomposites is lacking, and a systematic analysis of such strategy for combating a range of amyloid pathogeneses is missing. Here we review the history, principles and evolving chemistry of constructing peptido-nanocomposites from bottom up and discuss their future application against amyloid diseases that debilitate a significant portion of the global population.


Assuntos
Amiloidose , Nanocompostos , Humanos , Amiloidose/tratamento farmacológico , Amiloide/química , Peptídeos/química , Proteínas Amiloidogênicas/química , Peptídeos beta-Amiloides/química
10.
Biol Proced Online ; 25(1): 32, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38041016

RESUMO

BACKGROUND: Musashi-2 (MSI2) is a critical RNA-binding protein (RBP) whose ectopic expression drives the pathogenesis of various cancers. Accumulating evidence suggests that inducing ferroptosis of tumor cells can inhibit their malignant biological behavior as a promising therapeutic approach. However, it is unclear whether MSI2 regulates cell death in colorectal cancer (CRC), especially the underlying mechanisms and biological effects in CRC ferroptosis remain elusive. METHODS: Experimental methods including qRT‒PCR, immunofluorescence, flow cytometry, western blot, co-immunoprecipitation, CCK-8, colony formation assay, in vitro cell transwell migration and invasion assays, in vivo xenograft tumor experiments, liver and lung CRC metastasis models, CAC mice models, transmission electron microscopy, immunohistochemistry, histopathology, 4D label-free proteomics sequencing, bioinformatic and database analysis were used in this study. RESULTS: Here, we investigated that MSI2 was upregulated in CRC and positively correlated with ferroptosis inhibitor molecules. MSI2 deficiency suppressed CRC malignancy by inhibiting cell proliferation, viability, migration and invasion in vitro and in vivo; and MSI2 deficiency triggered CRC ferroptosis by changing the intracellular redox state (ROS levels and lipid peroxidation), erastin induced cell mortality and viability, iron homeostasis (intracellular total irons and ferrous irons), reduced glutathione (GSH) levels and mitochondrial injury. Mechanistically, through 4D-lable free proteomics analysis on SW620 stable cell lines, we demonstrated that MSI2 directly interacted with p-ERK and MSI2 knockdown downregulated the p-ERK/p38/MAPK axis signaling pathway, which further repressed MAPKAPK2 and HPSB1 phosphorylation, leading to decreased expression of PCNA and Ki67 and increased expression of ACSL4 in cancer cells. Furthermore, HSPB1 could rescue the phenotypes of MSI2 deficiency on CRC ferroptosis in vitro and in vivo. CONCLUSIONS: This study indicates that MSI2 deficiency suppresses the growth and survival of CRC cells and promotes ferroptosis by inactivating the MAPK signaling pathway to inhibit HSPB1 phosphorylation, which leads to downregulation of PCNA and Ki67 and upregulation of ACSL4 in cancer cells and subsequently induces redox imbalance, iron accumulation and mitochondrial shrinkage, ultimately triggering ferroptosis. Therefore, targeted inhibition of MSI2/MAPK/HSPB1 axis to promote ferroptosis might be a potential treatment strategy for CRC.

11.
J Virol ; 96(10): e0059822, 2022 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-35510863

RESUMO

Posttranslational modifications (PTMs) of viral proteins play critical roles in virus infection. The role of neddylation in enterovirus 71 (EV71) replication remains poorly defined. Here, we showed that the structural protein VP2 of EV71 can be modified by neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) in an E3 ligase X-linked inhibitor of apoptosis protein (XIAP)-dependent manner. Mutagenesis and biochemical analyses mapped the neddylation site at lysine 69 (K69) of VP2 and demonstrated that neddylation reduced the stability of VP2. In agreement with the essential role of VP2 in viral replication, studies with EV71 reporter viruses with wild-type VP2 (enhanced green fluorescent protein [EGFP]-EV71) and a K69R mutant VP2 (EGFP-EV71-VP2 K69R) showed that abolishment of VP2 neddylation increased EV71 replication. In support of this finding, overexpression of NEDD8 significantly inhibited the replication of wild-type EV71 and EGFP-EV71, but not EGFP-EV71-VP2 K69R, whereas pharmacologic inhibition of neddylation with the NEDD8-activating enzyme inhibitor MLN4924 promoted the replication of EV71 in biologically relevant cell types. Our results thus support the notion that EV71 replication can be negatively regulated by host cellular and pathobiological cues through neddylation of VP2 protein. IMPORTANCE Neddylation is a ubiquitin-like posttranslational modification by conjugation of neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) to specific proteins for regulation of their metabolism and biological activities. In this study, we demonstrated for the first time that EV71 VP2 protein is neddylated at K69 residue to promote viral protein degradation and consequentially suppress multiplication of the virus. Our findings advance knowledge related to the roles of VP2 in EV71 virulence and the neddylation pathway in the host restriction of EV71 infection.


Assuntos
Proteínas do Capsídeo , Enterovirus Humano A , Processamento de Proteína Pós-Traducional , Replicação Viral , Animais , Proteínas do Capsídeo/química , Linhagem Celular Tumoral , Chlorocebus aethiops , Enterovirus Humano A/fisiologia , Células HEK293 , Humanos , Proteína NEDD8/metabolismo , Células Vero , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo
12.
Psychol Med ; 53(4): 1390-1399, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36468948

RESUMO

BACKGROUND: Residual negative symptoms and cognitive impairment are common for chronic schizophrenia patients. The aim of this study was to investigate the efficacy of a mindfulness-based intervention (MBI) on negative and cognitive symptoms of schizophrenia patients with residual negative symptoms. METHODS: In this 6-week, randomized, single-blind, controlled study, a total of 100 schizophrenia patients with residual negative symptoms were randomly assigned to the MBI or control group. The 6-week MBI group and the control group with general rehabilitation programs maintained their original antipsychotic treatments. The scores for the Positive and Negative Syndrome Scale (PANSS), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and the Symptom Checklist 90 (SCL-90) were recorded at baseline and week 6 to assess psychotic symptoms, cognitive performance, and emotional state, respectively. RESULTS: Compared with general rehabilitation programs, MBI alleviated the PANSS-negative subscore, general psychopathology subscore, and PANSS total score in schizophrenia patients with residual negative symptoms (F = 33.77, pBonferroni < 0.001; F = 42.01, pBonferroni < 0.001; F = 52.41, pBonferroni < 0.001, respectively). Furthermore, MBI improved RBANS total score and immediate memory subscore (F = 8.80, pBonferroni = 0.024; F = 11.37, pBonferroni = 0.006), as well as SCL-90 total score in schizophrenia patients with residual negative symptoms (F = 18.39, pBonferroni < 0.001). CONCLUSIONS: Our results demonstrate that MBI helps schizophrenia patients with residual negative symptoms improve clinical symptoms including negative symptom, general psychopathology symptom, and cognitive impairment. TRIAL REGISTRATION: ChiCTR2100043803.


Assuntos
Antipsicóticos , Disfunção Cognitiva , Atenção Plena , Esquizofrenia , Humanos , Esquizofrenia/complicações , Esquizofrenia/terapia , Esquizofrenia/diagnóstico , Seguimentos , Método Simples-Cego , Antipsicóticos/uso terapêutico , Disfunção Cognitiva/terapia , Disfunção Cognitiva/tratamento farmacológico , Método Duplo-Cego
13.
Arch Microbiol ; 206(1): 41, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38147133

RESUMO

Vibrio parahaemolyticus is a significant cause of seafood-associated gastroenteritis and pestilence in aquaculture worldwide. Despite extensive research, strategies for protein depletion in this pathogen remain limited. Herein, we constructed a new CRISPR interference (CRISPRi) system for gene repression based on the combination of a shuttle vector pVv3 and the nuclease-null Cas9 variant (dead Cas9, or dCas9) from Streptococcus pyrogens. This CRISPRi is induced by adding both IPTG and arabinose. We showed that gene repression is scalable via the use of multiple sgRNAs. We also demonstrated that this gene repression can be precisely tuned by adjusting the amount of two different inducers and can be reversed by removing the inducers. This system provides a simple approach for selective gene repression on a genome-wide scale in V. parahaemolyticus. Application of this system will dramatically accelerate investigations of this bacterium, including studies of physiology, pathogenesis, and drug target discovery.


Assuntos
Vibrio parahaemolyticus , Vibrio parahaemolyticus/genética , RNA Guia de Sistemas CRISPR-Cas , Aquicultura , Arabinose , Descoberta de Drogas
14.
Inorg Chem ; 62(47): 19248-19255, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-37955232

RESUMO

Inorganic lead-free vacancy-ordered double perovskites with the chemical formula A2BX6 are promising candidates to overcome Pb-based organic-inorganic perovskite's toxicity and instability issues. We designed the mixed-halide double perovskites Cs2PdBr6-xIx by halogen anions substitution. The structure, stability, and electronic and photoelectric properties were explored using density functional theory (DFT). The negative value of the formation energy indicated that the Cs2PdBr6-xIx perovskites are thermodynamically stable. These perovskites exhibit tunable bandgap values in the range of 0.77-1.73 eV, which are direct or quasi-direct bandgaps except for Cs2PdBr3I3. Their absorption spectrum shows that the absorption range of visible light expands significantly. The theoretical spectral limit maximum efficiency (SLME) of Cs2PdBr5I with 1.3 eV and Cs2PdBr4I2 with 1.04 eV reached 32 and 30.4%, respectively, which are becoming comparable to or slightly surpassing CH3NH3PbI3, indicating they could be candidates for single-junction solar cells. In addition, the Cs2PdBr3I3 and the Cs2PdBr4I2, with the bandgap of 1.12 and 1.04 eV, respectively, could be the bottom cell to form the homogeneous tandem solar cells with the Cs2PdBr6, which could be the top cell with the bandgap of 1.73 eV.

15.
Bioorg Chem ; 134: 106458, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36933336

RESUMO

Six new oligostilbenes, carastilphenols A-E (1-5) and (-)-hopeachinol B (6), with three reported oligostilbenes were obtained from the stems of Caragana sinica. The structures of compounds 1-6 were determined by comprehensive spectroscopy analysis, and their absolute configurations were determined by electronic circular dichroism calculations. Thus, natural tetrastilbenes were determined as absolute configuration for the first time. Also, we did several pharmacological essays. In the antiviral tests, compounds 2, 4 and 6 showed moderate anti-coxsackie virus B3 type (CVB3) effect on Vero cells activities in vitro with IC50 values of 19.2 âˆ¼ 69.3 µM; and compounds 3 and 4 showed different levels of anti-respiratory syncytial virus (RSV) effect on Hep2 cells activities in vitro with IC50 values of 23.1 and 33.3 µM, respectively. As for hypoglycemic activity, compounds 6-9 (10 µM) showed the inhibition of α-glucosidase in vitro with IC50 values of 0.1 âˆ¼ 0.4 µM; and compound 7 showed significant inhibition (88.8%, 10 µM) of protein tyrosine phosphatase 1B (PTP1B) with IC50 value of 1.1 µM in vitro.


Assuntos
Caragana , Hipoglicemiantes , Animais , Chlorocebus aethiops , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Caragana/química , Caragana/metabolismo , Células Vero , Antivirais/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Estrutura Molecular
16.
Bioorg Chem ; 131: 106324, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36563414

RESUMO

Chemical investigation of an alcohol extract from the twigs and leaves of Illicium henryi Diels resulted in the isolation of two new acorane-related seco-sesquiterpenes (1 and 3), two new acorane-related seco-norsesquiterpenes (2 and 4), one new 2-epi-cedrane sesquiterpene (5), eight new acorane-type sesquiterpenes (6-13), and a known major constituent of acorenone B (14). Their structures were established by interpreting extensive spectroscopic data, including HRESIMS, NMR (1H and 13C NMR, 1H-1H COSY, HSQC, and HMBC), and NOE difference spectra analysis. The absolute configurations of 1, 2, 4-7, 9, 10, and 14 were determined by X-ray crystallography, while chemical transformation methods were performed with compound 14 as the starting material to elegantly solve the absolute configuration issue of compounds 8 and 11-13. Notably, 1 and 2 are seco-sesquiterpenes that are related to acorane and possess an unusual ketal-linked hemiacetal in a 6,8-dioxabicyclo[3.2.1]octan-7-ol scaffold ring system. Plausible biosynthetic pathways for compounds 1-14, which were derived from the acorane skeleton, were proposed. All the isolated compounds (1-14) were evaluated for their antiviral and cytotoxic activities.


Assuntos
Antivirais , Illicium , Sesquiterpenos , Antivirais/química , Antivirais/farmacologia , Illicium/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Folhas de Planta/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia
17.
Ecotoxicol Environ Saf ; 265: 115519, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37769580

RESUMO

Heavy metal (HM) stress is a non-negligible abiotic stress that seriously restricts crop yield and quality, while the sprout stage is the most sensitive to stress and directly impacts the growth and development of the later stage. Melatonin (N-acetyl-5-methoxytryptamine), as an exogenous additive, enhances stress resistance due to its ability to oxidize and reduce. However, few reports on exogenous melatonin to tiger nuts under HM stress have explored whether exogenous melatonin enhances plants' resistance to heavy metals. Here, "Jisha 2″ was used as material, with a stress concentration of 5 mg/L and 100 µmol/L of CdCl2 to explore whether exogenous melatonin enhances plant resistance and molecular mechanism. The result revealed that stress limits growth, while melatonin alleviated the sprout damage under stress from the phenotypes. Moreover, stress-enhanced reactive oxygen species (ROS) accumulation and membrane lipid peroxidation, while melatonin-increased ROS reduce damage via the analysis of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) and malondialdehyde (MDA) content, hydrogen peroxide (H2O2), superoxide anion (O2-), and Electrolyte leakage (El). Further results indicated that HM leads to DNA damage while exogenous melatonin will repair the damage by analyzing random amplified polymorphic DNA (RAPD), DNA cross-linking, 8-hydroxy-20-deoxyguanine level, and relative density of apurinic sites. Furthermore, gene expression in the DNA-repaired pathway exhibited similar results. These results applied that exogenous melatonin released the hurt caused by HM stress, with DNA repair and ROS balance serving as candidate pathways. This study elucidated the mechanism of melatonin's influence and provided theoretical insights into its application in tiger nuts.


Assuntos
Cyperus , Melatonina , Melatonina/farmacologia , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Cádmio/metabolismo , Peróxido de Hidrogênio/metabolismo , Técnica de Amplificação ao Acaso de DNA Polimórfico , DNA/metabolismo , Estresse Oxidativo
18.
Chem Biodivers ; 20(5): e202300248, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37080916

RESUMO

Two new ursane-type triterpenes, eburnealactones A and B (1 and 2), one new flavonoid, eburneatin A (6), and one new phenylethanoid glycoside, chiritoside D (7), along with 9 known compounds (3-5, 8-13) were isolated from the whole plant of Primulina eburnea. Their structures were elucidated by comprehensive spectroscopic data analysis (IR, UV, NMR, and HR-ESI-MS). All the compounds were evaluated for their cytotoxic activities. Compound 1 showed significant cytotoxic activities against MKN-45 cell lines and 5637 cell lines with the IC50 values of 9.57 µM and 8.30 µM, respectively. Compound 1 exhibited moderate cytotoxic activities against A549 and PATU8988T cell lines with the IC50 values of 30.70 µM and 38.22 µM, respectively. Compound 6 exhibited moderate cytotoxic activities against MKN-45, HCT116, PATU8988T, 5637 and A-673 cell lines with the IC50 values of 19.69 µM, 16.44 µM, 18.07 µM, 11.51 µM and 18.15 µM, respectively. Compound 5 showed moderate cytotoxic activities against A549 cell lines with the IC50 values of 24.06 µM.


Assuntos
Antineoplásicos , Triterpenos , Humanos , Estrutura Molecular , Glicosídeos/química , Antineoplásicos/farmacologia , Flavonoides , Células A549 , Triterpenos/farmacologia , Triterpenos/química
19.
Molecules ; 28(12)2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37375174

RESUMO

In order to remove and reuse the ecotoxic dye Eriochrome black T (EBT) from dyeing wastewater, we used a process called cetyltrimethylammonium bromide (CTAB)-assisted foam fractionation. By optimizing this process with response surface methodology, we achieved an enrichment ratio of 110.3 ± 3.8 and a recovery rate of 99.1 ± 0.3%. Next, we prepared composite particles by adding ß-cyclodextrin (ß-CD) to the foamate obtained through foam fractionation. These particles had an average diameter of 80.9 µm, an irregular shape, and a specific surface area of 0.15 m2/g. Using these ß-CD-CTAB-EBT particles, we were able to effectively remove trace amounts of Cu2+ ions (4 mg/L) from the wastewater. The adsorption of these ions followed pseudo-second-order kinetics and Langmuir isotherm models, and the maximal adsorption capacities at different temperatures were 141.4 mg/g at 298.15 K, 143.1 mg/g at 308.15 K, and 144.5 mg/g at 318.15 K. Thermodynamic analysis showed that the mechanism of Cu2+ removal via ß-CD-CTAB-EBT was spontaneous and endothermic physisorption. Under the optimized conditions, we achieved a removal ratio of 95.3 ± 3.0% for Cu2+ ions, and the adsorption capacity remained at 78.3% after four reuse cycles. Overall, these results demonstrate the potential of ß-CD-CTAB-EBT particles for the recovery and reuse of EBT in dyeing wastewater.

20.
Angew Chem Int Ed Engl ; 62(49): e202313325, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-37818672

RESUMO

Photocatalytic organic functionalization reactions represent a green, cost-effective, and sustainable synthesis route for value-added chemicals. However, heterogeneous photocatalysis is inefficient in directly activating ammonia molecules for the production of high-value-added nitrogenous organic products when compared with oxygen activation in the formation of related oxygenated compounds. In this study, we report the heterogeneous photosynthesis of benzonitriles by the ammoxidation of benzyl alcohols (99 % conversion, 93 % selectivity) promoted using BiOBr nanosheets with surface vacancy associates. In contrast, the main reaction of catalysts with other types of vacancy sites is the oxidation of benzyl alcohol to benzaldehyde or benzoic acid. Experimental measurements and theoretical calculations have demonstrated a specificity of vacancy type with respect to product selectivity, which arises from the adsorption and activation of NH3 and O2 that is required to promote subsequent C-N coupling and oxidation to nitrile. This study provides a better understanding of the role of vacancies as catalytic sites in heterogeneous photocatalysis.

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