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1.
Inorg Chem ; 63(15): 6734-6742, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38570330

RESUMO

The design of multimetal catalysts holds immense significance for efficient CO2 capture and its conversion into economically valuable chemicals. Herein, heterobimetallic catalysts (MiMo)L were exploited for the CO2 reduction reactions (CO2RR) using relativistic density functional theory (DFT). The octadentate Pacman-like polypyrrolic ligand (H4L) accommodates two metal ions (Mo, W, Nd, and U) inside (Mi) and outside (Mo) its month, rendering a weak bimetal coupling-assisted MN4 catalytically active site. Adsorption reactions have access to energetically stable coordination modes of -OCO, -OOC, and -(OCO)2, where the donor atom(s) are marked in bold. Among all of the species, (UiMoo)L releases the most energy. Along CO2RR, it favors to produce CO. The high-efficiency CO2 reduction is attributed to the size matching of U with the ligand mouth and the effective manipulation of the electron density of both ligand and bimetals. The mechanism in which heterobimetals synergetically capture and reduce CO2 has been postulated. This establishes a reference in elaborating on the complicated heterogeneous catalysis.

2.
Biomolecules ; 14(3)2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38540757

RESUMO

Chemokines are cytokines with chemoattractant capacities that exert their physiological functions through the binding of chemokine receptors. Thus, chemokine and receptor complexes exert important roles in regulating development and homeostasis during routine immune surveillance and inflammation. Compared to mammals, the physiology and structure of chemokine receptors in fish have not been systematically studied. Furthermore, the salmonid-specific whole genome duplication has significantly increased the number of functional paralogs of chemokine receptors. In this context, in the current study, trout exhibited 17 cxcr genes, including 12 newly identified and 5 previously identified receptors. Interestingly, gene expression of brain cxcr1 and cxcr4, kidney cxcr3 and cxcr4, and spleen cxcr3, cxcr4, and cxcr5 subtypes were altered by bacterial infection, whereas brain cxcr1, kidney cxcr1 and cxcr7, and liver cxcr2, cxcr3, and cxcr4 subtypes were changed in response to environmental changes. Based on protein structures predicted by ColabFold, the conserved amino acids in binding pockets between trout CXCR4.1 subtypes and human CXCR4 were also analyzed. Our study is valuable from a comparative point of view, providing new insights into the identification and physiology of salmonid chemokine receptors.


Assuntos
Oncorhynchus mykiss , Animais , Humanos , Oncorhynchus mykiss/genética , Genoma , Transdução de Sinais , Mamíferos/genética
3.
Hum Exp Toxicol ; 43: 9603271231218707, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487884

RESUMO

BACKGROUND: Bupivacaine (BUP), a long-acting local anesthetic, has been widely used in analgesia and anesthesia. However, evidence strongly suggests that excessive application of BUP may lead to neurotoxicity in neurons. Sphingosine kinase 2 (SPHK2) has been reported to exert neuroprotective effects. In this study, we intended to investigate the potential role and mechanism of SPHK2 in BUP-induced neurotoxicity in dorsal root ganglion (DRG) neurons. METHODS: DRG neurons were cultured with BUP to simulate BUP-induced neurotoxicity in vitro. CCK-8, LDH, and flow cytometry assays were performed to detect the viability, LDH activity, and apoptosis of DRG neurons. RT-qPCR and western blotting was applied to measure gene and protein expression. Levels. MeRIP-qPCR was applied for quantification of m6A modification. RIP-qPCR was used to analyze the interaction between SPHK2 and YTHDF1. RESULTS: SPHK2 expression significantly declined in DRG neurons upon exposure to BUP. BUP challenge substantially reduced the cell viability and increased the apoptosis rate in DRG neurons, which was partly abolished by SPHK2 upregulation. YTHDF1, an N6-methyladenosine (m6A) reader, promoted SPHK2 expression in BUP-treated DRG neurons in an m6A-dependent manner. YTHDF1 knockdown partly eliminated the increase in SPHK2 protein level and the protection against BUP-triggered neurotoxicity in DRG neurons mediated by SPHK2 overexpression. Moreover, SPHK2 activated the PI3K/AKT signaling to protect against BUP-induced cytotoxic effects on DRG neurons. CONCLUSIONS: In sum, YTHDF1-mediated SPHK2 upregulation ameliorated BUP-induced neurotoxicity in DRG neurons via promoting activation of the PI3K/AKT signaling pathway.


Assuntos
Bupivacaína , Síndromes Neurotóxicas , Fosfotransferases (Aceptor do Grupo Álcool) , Humanos , Bupivacaína/toxicidade , Regulação para Cima , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Síndromes Neurotóxicas/prevenção & controle , Apoptose , Proteínas de Ligação a RNA
4.
Int J Biol Macromol ; 255: 128274, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37989432

RESUMO

Heavy metal ions (HMIs) have been widely applied in various industries because of their excellent physicochemical properties. However, their discharging without appropriate treatment brought about serious pollution problems. So it is desirable but challenging to rapidly and completely clean up these toxic pollutants from water, especially utilizing environmentally friendly and naturally rich biomass materials. In this work, we prepared nanocellulose/carbon dots/magnesium hydroxide (CCMg) ternary composite using cotton via a simple hydrothermal method. The removal mechanism towards Cd2+ and Cu2+ was investigated using a combination of experimental techniques and density functional theory calculations. CCMg shows a good ability to remove HMIs. It is realized that the interaction between each component of CCMg and cadmium nitrate is mainly of hydrogen/dative bonds. Cadmium nitrate is preferentially enriched by the Mg(OH)2 moiety, proved by calculated thermodynamics, interfacial interactions and charges. After transformation, the cadmium carbonate precipitate is fixed on the surface by nanocellulose (NC) via chemical coupling; and of interest is that copper ion precipitates in the form of basic sulfate. Due to its high adsorption effect and simple recovery operation, CCMg is having a wide range of application prospects as a water treatment agent.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Águas Residuárias , Carbono , Metais Pesados/química , Cádmio/química , Nitratos , Adsorção , Íons , Poluentes Químicos da Água/química , Cinética , Concentração de Íons de Hidrogênio
5.
J Neurol ; 271(2): 918-928, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37848650

RESUMO

BACKGROUND: Many neuroscience and neurology studies have forced a reconsideration of the traditional motor-related scope of cerebellar function, which has now expanded to include various cognitive functions. Spinocerebellar ataxia type 3 (SCA3; the most common hereditary ataxia) is neuropathologically characterized by cerebellar atrophy and frequently presents with cognitive impairment. OBJECTIVE: To characterize cognitive impairment in SCA3 and investigate the cerebellum-cognition associations. METHODS: This prospective, cross-sectional cohort study recruited 126 SCA3 patients and 41 healthy control individuals (HCs). Participants underwent a brain 3D T1-weighted images as well as neuropsychological tests. Voxel-based morphometry (VBM) and region of interest (ROI) approaches were performed on the 3D T1-weighted images. CERES was used to automatically segment cerebellums. Patients were grouped into cognitively impaired (CI) and cognitively preserved (CP), and clinical and MRI parameters were compared. Multivariable regression models were fitted to examine associations between cerebellar microstructural alterations and cognitive domain impairments. RESULTS: Compared to HCs, SCA3 patients showed cognitive domain impairments in information processing speed, verbal memory, executive function, and visuospatial perception. Between CI and CP subgroups, the CI subgroup was older and had lower education, as well as higher severity scores. VBM and ROI analyses revealed volume loss in cerebellar bilateral lobule VI, right lobule Crus I, and right lobule IV of the CI subgroup, and all these cerebellar lobules were associated with the above cognitive domain impairments. CONCLUSIONS: Our findings demonstrate the multiple cognitive domain impairments in SCA3 patients and indicate the responsible cerebellar lobules for the impaired cognitive domain(s).


Assuntos
Disfunção Cognitiva , Doença de Machado-Joseph , Humanos , Cerebelo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Estudos Transversais , Doença de Machado-Joseph/complicações , Doença de Machado-Joseph/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Estudos Prospectivos
6.
Cell Mol Biol (Noisy-le-grand) ; 69(12): 118-123, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38063108

RESUMO

Thyroid cancer (TC) originates from thyroid epithelial cells and is one of the common malignant tumors in the endocrine system. The aim of our study was to explore the dynamic changes of serum miR-105-3p expression after TC surgery and its correlation with clinicopathological manifestations, and evaluate its clinical value as a potential biomarker after surgery. A total of 100 TC patients were selected as the research objects. To detect serum miR-105-3p in patients and its correlation with tumor pathological characteristics and the dynamic changes of postoperative serum miR-105-3p in patients to evaluate its prognostic value as a potential biomarker. Serum miR-105-3p increases in patients with well-differentiated TC and lymph node metastasis; Serum miR-105-3p gradually decreases after surgery, and there is a significant difference between 4 days after surgery and before surgery,  serum miR-105-3p level can significantly distinguish between patients with poor prognosis and good prognosis within 2 years after the operation, and it can predict the improvement of the prognosis of TC after surgery. The level of serum miR-105-3p is closely related to tumor differentiation and lymph node metastasis in TC patients. Its level gradually decreases with the passage of time after surgery. It has a good diagnostic value for the prognosis of TC after surgery and is expected to become a TC surgery. Potential biomarkers for post-diagnosis.


Assuntos
MicroRNAs , Neoplasias da Glândula Tireoide , Humanos , Metástase Linfática , Prognóstico , MicroRNAs/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/cirurgia , Biomarcadores , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica
7.
BMC Complement Med Ther ; 23(1): 415, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978381

RESUMO

BACKGROUND: Cardiovascular disease and cancer are the main causes of morbidity and mortality worldwide. Studies have shown that these two diseases may have some common risk factors. Atorvastatin is mainly used for the treatment of atherosclerosis in clinic. A large number of studies show that atorvastatin may produce anti-tumor activities. This study aimed to predict the common targets of atorvastatin against atherosclerosis and non-small cell lung cancer (NSCLC) based on network pharmacology. METHODS: The target genes of atherosclerosis and NSCLC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The disease-target-component model map and the core network were obtained using Cytoscape 3.7.1. The MTS and wound healing assay were used to detect the effect of atorvastatin on cell viability and migration of A549 cells. The expression of potential common target genes of atorvastatin against atherosclerosis and NSCLC were confirmed in A549 cells and lung cancer tissues of patients. RESULTS: We identified 15 identical pathogenic genes, and four of which (MMP9, MMP12, CD36, and FABP4) were considered as the key target genes of atorvastatin in anti-atherosclerosis and NSCLC. The MTS and wound healing assays revealed that atorvastatin decreased A549 cells migration significantly. Atorvastatin markedly decreased the expression of MMP9, MMP12, CD36, and FABP4 in A549 cells and patients were treated with atorvastatin. CONCLUSIONS: This study demonstrated 15 common pathogenic genes in both atherosclerosis and NSCLC. And verified that MMP 9, MMP 12, CD 36 and FABP 4 might be the common target genes of atorvastatin in anti-atherosclerosis and NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/uso terapêutico , Atorvastatina/farmacologia , Atorvastatina/uso terapêutico , Metaloproteinase 12 da Matriz/uso terapêutico
8.
J Invertebr Pathol ; 201: 108013, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37923117

RESUMO

Infectious hypodermal and hematopoietic necrosis virus (IHHNV) is one of the linearly single-stranded DNA viruses. Ecytonucleospora hepatopenaei (EHP) is an intracellular parasitic microsporidian. IHHNV and EHP are pathogens that have been widely prevalent in shrimp farming. Both of them are associated with growth retardation of the penaeid shrimp, which causes serious economic losses to shrimp farming. Shrimp can be co-infected with IHHNV and EHP. In this study, a rapid duplex polymerase chain reaction (PCR) was developed and optimized for the simultaneous detection of EHP and IHHNV. The detection limit of the duplex PCR could reach 1.5 × 102 copies for EHP and IHHNV. A total of 578 Litopenaeus vannamei samples were detected by the established duplex PCR detection method. The results suggested that 398 samples were infected with EHP, 362 samples were infected with IHHNV, and 265 samples were co-infected with EHP and IHHNV. The case-control analysis of the detected shrimp samples showed a certain synergistic effect between EHP and IHHNV.


Assuntos
Densovirinae , Microsporídios , Penaeidae , Animais , Densovirinae/genética , Reação em Cadeia da Polimerase/métodos , Agricultura , Microsporídios/genética
9.
Biomed Pharmacother ; 167: 115619, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37804813

RESUMO

Kurarinone, a major lavandulyl flavanone found in the roots of Sophora flavescens aiton, has been reported to exhibit anti-inflammatory and anti-oxidative activities in lipopolysaccharide (LPS)-induced macrophages; however, the effects of kurarinone on the activation of NLRP3 inflammasome and the protective effects against sepsis have not been well investigated. In this study, we aimed to investigate the impacts of kurarinone on NLRP3 inflammasome activation in lipopolysaccharide (LPS)-induced macrophages and its protective effects against sepsis in vivo. Secretion of pro-inflammatory cytokines, activation of MAPKs and NF-κB signaling pathways, formation of NLRP3 inflammasome, and production of reactive oxygen species (ROS) by LPS-induced macrophages were examined; additionally, in vivo LPS-induced endotoxemia model was used to investigate the protective effects of kurarinone in sepsis-induced damages. Our experimental results demonstrated that kurarinone inhibited the expression of iNOS and COX-2, suppressed the phosphorylation of MAPKs, attenuated the production of TNF-α, IL-6, nitric oxide (NO) and ROS, repressed the activation of the NLRP3 inflammasome, and impeded the maturation and secretion of IL-1ß and caspase-1. Furthermore, the administration of kurarinone attenuated the infiltration of neutrophils in the lung, kidneys and liver, reduced the expression of organ damage markers, and increased the survival rate in LPS-challenged mice. Collectively, our study demonstrated that kurarinone can protect against LPS-induced sepsis damage and exert anti-inflammatory effects via inhibiting MAPK/NF-κB pathways, attenuating NLRP3 inflammasome formation, and preventing intracellular ROS accumulation, suggesting that kurarinone might have potential for treating sepsis and inflammation-related diseases.


Assuntos
Inflamassomos , Sepse , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Lipopolissacarídeos/toxicidade , Espécies Reativas de Oxigênio/metabolismo , NF-kappa B/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Sepse/induzido quimicamente , Sepse/tratamento farmacológico
10.
Biochem Pharmacol ; 216: 115807, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37716621

RESUMO

Small cell lung cancer (SCLC) is a highly lethal subtype of lung cancer with few therapeutic options; therefore, the identification of new targets and drugs with potent combination therapy is desirable. We previously screened BH3 mimetics from a natural product library, and in this study, we validated nobiletin as a BH3 mimetic. Specifically, we observed its combination potential and mechanism with vorinostat in SCLC in vitro and in vivo. The results showed that combination treatment with nobiletin and vorinostat reduced the proliferation of SCLC H82 cells and increased the levels of apoptotic proteins such as cleaved caspase-9 and cleaved PARP. The combination treatment increased LC3-II expression and induced autophagic cell death. In addition, this treatment significantly inhibited H82 cell xenograft SCLC tumor growth in nude mice. The combination treatment with nobiletin and vorinostat efficiently increased autophagy by inhibiting the PI3K-AKT-mTOR pathway and promoting dissociation of the BCL-2 and Beclin 1 complex, increasing the level of isolated Beclin 1 to stimulate autophagy. Molecular docking and surface plasmon resonance analysis showed that nobiletin stably bound to the BCL-2, BCL-XL and MCL-1 proteins with high affinity in a concentration-dependent manner. These results suggest that nobiletin is a BH3-only protein mimetic. Furthermore, the combination of nobiletin with vorinostat increased histone H3K9 and H3K27 acetylation levels in SCLC mouse tumor tissue and enhanced the expression of the BH3-only proteins BIM and BID. We conclude that nobiletin is a novel natural BH3 mimetic that can cooperate with vorinostat to induce apoptosis and autophagy in SCLC.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Animais , Camundongos , Vorinostat/farmacologia , Vorinostat/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Proteína Beclina-1 , Camundongos Nus , Fosfatidilinositol 3-Quinases , Simulação de Acoplamento Molecular , Apoptose , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Autofagia , Linhagem Celular Tumoral
11.
Mov Disord ; 38(9): 1750-1755, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37394769

RESUMO

OBJECTIVES: To diagnose the molecular cause of hereditary spastic paraplegia (HSP) observed in a four-generation family with autosomal dominant inheritance. METHODS: Multiplex ligation-dependent probe amplification (MLPA), whole-exome sequencing (WES), and RNA sequencing (RNA-seq) of peripheral blood leukocytes were performed. Reverse transcription polymerase chain reaction (RT-PCR) and Sanger sequencing were used to characterize target regions of SPAST. RESULTS: A 121-bp AluYb9 insertion with a 30-bp poly-A tail flanked by 15-bp direct repeats on both sides was identified in the edge of intron 16 in SPAST that segregated with the disease phenotype. CONCLUSIONS: We identified an intronic AluYb9 insertion inducing splicing alteration in SPAST causing pure HSP phenotype that was not detected by routine WES analysis. Our findings suggest RNA-seq is a recommended implementation for undiagnosed cases by first-line diagnostic approaches. © 2023 International Parkinson and Movement Disorder Society.


Assuntos
Paraplegia Espástica Hereditária , Humanos , Paraplegia Espástica Hereditária/genética , Paraplegia Espástica Hereditária/diagnóstico , Espastina/genética , Adenosina Trifosfatases/genética , Fenótipo , Íntrons/genética , Mutação
12.
Inorg Chem ; 62(27): 10762-10771, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37377386

RESUMO

The successful management and safe disposal of high-level nuclear waste necessitate the efficient separation of actinides (An) from lanthanides (Ln), which has emerged as a crucial prerequisite. Mixed donor ligands incorporating both soft and hard donor atoms have garnered interest in the field of An/Ln separation and purification. One such example is nitrilotriacetamide (NTAamide) derivatives, which have demonstrated selectivity in extracting minor actinide Am(III) ions over Eu(III) ions. Nevertheless, the Am/Eu complexation behavior and selectivity remain underexplored. In the work, a comprehensive and systematic investigation has been conducted for [M(RL)(NO3)3] complexes (M = Am and Eu) utilizing relativistic density functional theory. The NTAamide ligand (RL) is substituted with various alkyl groups, namely, methyl, ethyl, propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, and n-octyl. Thermodynamic calculations show that the alkyl chain length in NTAamide is capable of tuning the separation selectivity of Am and Eu. Moreover, the differences in calculated free energies between Am and Eu complexes are more negative for R = Bu-Oct than Me-Pr. This indicates that elongation of the alkyl chain can increase the efficiency of selective separation of Am(III) from Eu(III). Based on the quantum theory of atoms in molecules and charge decomposition analyses, it has been observed that the strength of Am-RL bonds is higher than that of Eu-RL bonds. This disparity is attributed to a greater degree of covalency in Am-RL bonds and a higher level of charge transfer from ligands to Am within complexes containing these bonds. Energies of occupied orbitals with the central N character are recognized overall lower for [Am(OctL)(NO3)3] than for [Eu(OctL)(NO3)3], indicative of stronger complexation stability of the former. These results offer valuable insights into the separation mechanism of NTAamide ligands, which can help guide the development of more powerful agents for An/Ln separation in future applications.

13.
Artigo em Inglês | MEDLINE | ID: mdl-37328133

RESUMO

Perfluorocaproic acid (PFHxA), a short-chain substitute for the emerging contaminant perfluorinated compounds, has been detected in the aquatic environment. However, its aquatic toxicity and health risk assessment are mainly unknown. In this study, we compared the toxic doses of 0 mg/L, 5 mg/L, 15 mg/L, 45 mg/L and 135 mg/L on the pathological damage to tissue sections, antioxidant indexes and inflammatory factor expressions in liver, spleen, kidney, Prosogaster, Mid-gut, Hid-gut as well as the changes of IgM, C3, C4, LZM, GOT, GPT in serum of crucian carp. We determined the response of the intestinal microbial community to PFHxA stress by 16S. The results showed that the growth performance of crucian carp was slowed with the increase of PFHxA dose, which caused different degrees of damage to the tissues. Meanwhile, the indexes of SOD, GSH-Px, T-AOC, ACP, AKP and LZM in each tissue were reduced, and the indexes of IgM, C3, C4 and LZM in serum were reduced. The levels of MDA, GOT and GPT in tissues and GOT and GPT in serum were promoted. In addition, IL-1ß, TNF-α, NF-KB, and KEAP-1 in each tissue increased compared with the control group. The levels of IL-10, Nrf2, CAT, and GPx were decreased. The 16S rRNA gene sequencing results showed that PFHxA significantly reduced the abundance and diversity of the gut microbiota. It is suggested that PFHxA is likely to cause different degrees of damage to various tissues by disrupting the diversity of the intestinal flora. These results provide insights to facilitate the risk assessment of PFHxA contaminants in the aquatic environment.


Assuntos
Carpas , Microbioma Gastrointestinal , Animais , Carpa Dourada , RNA Ribossômico 16S , Imunoglobulina M
14.
Int J Mol Sci ; 24(8)2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37108458

RESUMO

Microglia-associated neuroinflammation is recognized as a critical factor in the pathogenesis of neurodegenerative diseases; however, there is no effective treatment for the blockage of neurodegenerative disease progression. In this study, the effect of nordalbergin, a coumarin isolated from the wood bark of Dalbergia sissoo, on lipopolysaccharide (LPS)-induced inflammatory responses was investigated using murine microglial BV2 cells. Cell viability was assessed using the MTT assay, whereas nitric oxide (NO) production was analyzed using the Griess reagent. Secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) was detected by the ELISA. The expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, mitogen-activated protein kinases (MAPKs) and NLRP3 inflammasome-related proteins was assessed by Western blot. The production of mitochondrial reactive oxygen species (ROS) and intracellular ROS was detected using flow cytometry. Our experimental results indicated that nordalbergin ≤20 µM suppressed NO, IL-6, TNF-α and IL-1ß production; decreased iNOS and COX-2 expression; inhibited MAPKs activation; attenuated NLRP3 inflammasome activation; and reduced both intracellular and mitochondrial ROS production by LPS-stimulated BV2 cells in a dose-dependent manner. These results demonstrate that nordalbergin exhibits anti-inflammatory and anti-oxidative activities through inhibiting MAPK signaling pathway, NLRP3 inflammasome activation and ROS production, suggesting that nordalbergin might have the potential to inhibit neurodegenerative disease progression.


Assuntos
Lipopolissacarídeos , Doenças Neurodegenerativas , Camundongos , Animais , Lipopolissacarídeos/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Microglia/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Doenças Neuroinflamatórias , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Doenças Neurodegenerativas/metabolismo , Transdução de Sinais , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo
15.
Am J Chin Med ; 51(4): 1019-1039, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37120705

RESUMO

Prostate cancer (PCa) is the second most prevalent cancer in men worldwide. The majority of PCa incidences eventually progress to castration-resistant PCa (CRPC), thereby establishing an urgent need for new effective therapeutic strategies. This study aims to examine the effects of morusin, a prenylated flavonoid isolated from Morus alba L., on PCa progression and identify the regulatory mechanism of morusin. Cell growth, cell migration and invasion, and the expression of EMT markers were examined. Cycle progression and cell apoptosis were examined using flow cytometry and a TUNEL assay, while transcriptome analysis was performed using RNA-seq with results being further validated using real-time PCR and western blot. A xenograft PCa model was used to examine tumor growth. Our experimental results indicated that morusin significantly attenuated the growth of PC-3 and 22Rv1 human PCa cells; moreover, morusin significantly suppressed TGF-[Formula: see text]-induced cell migration and invasion and inhibited EMT in PC-3 and 22Rv1 cells. Significantly, morusin treatment caused cell cycle arrest at the G2/M phase and induced cell apoptosis in PC-3 and 22Rv1 cells. Morusin also attenuated tumor growth in a xenograft murine model. The results of RNA-seq indicated that morusin regulated PCa cells through the Akt/mTOR signaling pathway, while our western blot results confirmed that morusin suppressed phosphorylation of AKT, mTOR, p70S6K, and downregulation of the expression of Raptor and Rictor in vitro and in vivo. These results suggest that morusin has antitumor activities on regulating PCa progression, including migration, invasion, and formation of metastasis, and might be a potential drug for CRPC treatment.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Masculino , Humanos , Animais , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Linhagem Celular Tumoral , Transdução de Sinais/genética , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Proliferação de Células/genética , Apoptose/genética , Movimento Celular
16.
Org Lett ; 25(16): 2939-2943, 2023 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-37078609

RESUMO

We report a new serine/threonine ligation (STL)-assisted diaminodiacid (DADA) strategy for the flexible construction of disulfide surrogates by the option of more abundant -Aa-Ser/Thr- ligation sites. The practicality of this strategy was evidenced by the synthesis of the intrachain disulfide surrogate of C-type natriuretic peptide and the interchain disulfide surrogate of insulin.


Assuntos
Serina , Treonina , Dissulfetos , Peptídeos
17.
Chemosphere ; 324: 138325, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36889472

RESUMO

It is desirable but challenging to sense toxic nitrogen dioxide (NO2) for it has become one of the most prominent air pollutants. Zinc oxide-based gas sensors are known to detect NO2 gas efficiently, however, the sensing mechanism and involved intermediates structures remain underexplored. In the work, a series of sensitive materials, including zinc oxide (ZnO) and its composites ZnO/X [X = Cel (cellulose), CN (g-C3N4) and Gr (graphene)] have been comprehensively examined by density functional theory. It is found that ZnO favors adsorbing NO2 over ambient O2, and produces nitrate intermediates; and H2O is chemically held by zinc oxide, in line with the non-negligible impact of humidity on the sensitivity. Of the formed composites, ZnO/Gr exhibits the best NO2 gas-sensing performance, which is proved by the calculated thermodynamics and geometrical/electronic structures of reactants, intermediates and products. The interfacial interaction has been elaborated on for composites (ZnO/X) as well as their complexes (ZnO- and ZnO/X-adsorbates). The current study well explains experimental findings and opens up a way to design and unearth novel NO2 sensing materials.


Assuntos
Poluentes Atmosféricos , Grafite , Óxido de Zinco , Óxido de Zinco/química , Grafite/química , Dióxido de Nitrogênio/análise , Poluentes Atmosféricos/análise , Celulose
18.
Int J Biol Macromol ; 237: 124194, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36972825

RESUMO

To solve pollution problem of heavy metal ions (HMIs) and recover them for sustainable development, a high-efficient-sewage treatment agent, carbon dots/cellulose nanofiber/Mg(OH)2 (CCMg), has been fabricated via a simple hydrothermal method. A variety of characterizations show that cellulose nanofiber (CNF) formed a layered-net structure. Hexagonal Mg(OH)2 flakes of about 100 nm has been attached on CNF. Carbon dots (CDs) around 10-20 nm in size were produced from CNF and distributed along CNF. The extraordinary structural feature endows CCMg with high removal performance towards HMIs. The up-taken capacities reach 992.8 and 667.3 mg g-1 for Cd2+ and Cu2+, respectively. The composite bears excellent durability in treating wastewater. Notably, the qualification of the drinking water can be satisfied while applying CCMg to handle Cu2+ wastewater. The mechanism of removal process has been proposed. Practically, Cd2+/Cu2+ ions were immobilized by CNF due to the space confinement effect. It achieves the facile separation and recovery of HMIs from the sewage, and more importantly, eliminates the risk of secondary contamination.


Assuntos
Metais Pesados , Nanofibras , Hidróxido de Magnésio , Carbono , Celulose/química , Nanofibras/química , Águas Residuárias , Esgotos , Metais Pesados/química , Íons/química
19.
Int J Mol Sci ; 24(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36675089

RESUMO

Active packaging materials protect food from deterioration and extend its shelf life. In the quest to design intriguing packaging materials, biocomposite ZnO/plant polyphenols/cellulose/polyvinyl alcohol (ZnPCP) was prepared via simple hydrothermal and casting methods. The structure and morphology of the composite were fully analyzed using XRD, FTIR, SEM and XPS. The ZnO particles, plant polyphenols (PPL) and cellulose were found to be dispersed in PVA. All of these components share their unique functions with the composite's properties. This study shows that PPL in the composite not only improves the ZnO dispersivity in PVA as a crosslinker, but also enhances the water barrier of PVA. The ZnO, PPL and cellulose work together, enabling the biocomposite to perform as a good food packaging material with only a 1% dosage of the three components in PVA. The light shielding investigation showed that ZnPCP-10 can block almost 100% of both UV and visible light. The antibacterial activities were evaluated by Gram-negative Escherichia coli (E. coli) and Gram-positive staphylococcus aureus (S. aureus), with 4.4 and 6.3 mm inhibition zones, respectively, being achieved by ZnPCP-10. The enhanced performance and easy degradation enables the biocomposite ZnPCP to be a prospect material in the packaging industry.


Assuntos
Quitosana , Óxido de Zinco , Embalagem de Alimentos , Álcool de Polivinil/química , Celulose/química , Óxido de Zinco/química , Quitosana/química , Staphylococcus aureus , Escherichia coli , Antibacterianos/farmacologia , Antibacterianos/química
20.
Chem Biodivers ; 20(2): e202201111, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36546830

RESUMO

Leptosperols C-G (1-5), five new phenylpropanoyl phloroglucinol derivatives were isolated from the leaves of Leptospermum scoparium. Compounds 1-3 are phenylpropanoyl phloroglucinol-sesquiterpene adducts with new carbon skeletons. Their structures with absolute configurations were elucidated by detailed spectroscopic analyses, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculation. Compounds 2 and 3 exhibited moderate anti-inflammatory activity in zebrafish acute inflammatory models.


Assuntos
Leptospermum , Floroglucinol , Animais , Leptospermum/química , Estrutura Molecular , Floroglucinol/química , Peixe-Zebra , Cristalografia por Raios X
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