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1.
Biomark Res ; 11(1): 15, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36726125

RESUMO

Extensive clinical and experimental evidence suggests that macrophages play a crucial role in cancer immunotherapy. Cluster of differentiation (CD) 47, which is found on both healthy and malignant cells, regulates macrophage-mediated phagocytosis by sending a "don't eat me" signal to the signal regulatory protein alpha (SIRPα) receptor. Increasing evidence demonstrates that blocking CD47 interaction with SIRPα can enhance cancer cell clearance by macrophages. Additionally, inhibition of CD47/SIRPα interaction can increase antigen cross-presentation, leading to T-cell priming and an activated adaptive antitumor immune response. Therefore, inhibiting CD47/SIRPα axis has a significant impact on tumor immunotherapy. Studies on CD47 monoclonal antibodies are at the forefront of research, and impressive results have been obtained. Nevertheless, hematotoxicity, especially anemia, has become the most common adverse effect of the CD47 monoclonal antibody. More specific targeted drugs (i.e., bispecific antibodies, SIRPα/Fc fusion protein antibodies, and small-molecule inhibitors) have been developed to reduce hematotoxicity. Here, we review the present usage of CD47 antagonists for the treatment of lymphomas and hematologic neoplasms from the perspectives of structure, function, and clinical trials, including a comprehensive overview of the drugs in development.

2.
Bioorg Med Chem Lett ; : 129166, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36736495

RESUMO

Tubulin, a potential target for antitumor drug discovery, contains three main binding sites for clinical inhibitors: colchicine, vinblastine, and paclitaxel. CA-4 has been reported to be a classic tubulin inhibitor targeting the colchicine site. Herein, based on the structural modification of CA-4, 48 novel compounds were designed and synthesized by selecting structural fragments with various biological activities to replace the cis double bond of CA-4. Among these compounds, compound 8p was the most effective tubulin inhibitor (IC50=65nM in HepG2 cells). Immunofluorescence experiment confirmed the anti-tumor effect of 8p by destroying the network structure of microtubules. Further studies showed that 8p induced tumor cell apoptosis, arrested cell cycle, inhibited tumor cell migration and invasion.

4.
Adv Cancer Res ; 157: 251-291, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36725112

RESUMO

The heparan sulfate proteoglycans (HSPGs) are glycoproteins that consist of a proteoglycan "core" protein and covalently attached heparan sulfate (HS) chain. HSPGs are ubiquitously expressed in mammalian cells on the cell surface and in the extracellular matrix (ECM) and secretory vesicles. Within HSPGs, the protein cores determine when and where HSPG expression takes place, and the HS chains mediate most of HSPG's biological roles through binding various protein ligands, including cytokines, chemokines, growth factors and receptors, morphogens, proteases, protease inhibitors, and ECM proteins. Through these interactions, HSPGs modulate cell proliferation, adhesion, migration, invasion, and angiogenesis to display essential functions in physiology and pathology. Under physiological conditions, the expression and localization of HSPGs are finely regulated to orchestrate their physiological functions, and this is disrupted in cancer. The HSPG dysregulation elicits multiple oncogenic signaling, including growth factor signaling, ECM and Integrin signaling, chemokine and immune signaling, cancer stem cell, cell differentiation, apoptosis, and senescence, to prompt cell transformation, proliferation, tumor invasion and metastasis, tumor angiogenesis and inflammation, and immunotolerance. These oncogenic roles make HSPGs an attractive pharmacological target for anti-cancer therapy. Several therapeutic strategies have been under development, including anti-HSPG antibodies, peptides and HS mimetics, synthetic xylosides, and heparinase inhibitors, and shown promising anti-cancer efficacy. Therefore, much progress has been made in this line of study. However, it needs to bear in mind that the roles of HSPGs in cancer can be either oncogenic or tumor-suppressive, depending on the HSPG and the cancer cell type with the underlying mechanisms that remain obscure. Further studies need to address these to fill the knowledge gap and rationalize more efficient therapeutic targeting.


Assuntos
Proteoglicanas de Heparan Sulfato , Neoplasias , Animais , Humanos , Proteoglicanas de Heparan Sulfato/metabolismo , Proteoglicanas de Heparan Sulfato/uso terapêutico , Neoplasias/patologia , Heparitina Sulfato/metabolismo , Heparitina Sulfato/uso terapêutico , Neovascularização Patológica/tratamento farmacológico , Diferenciação Celular , Mamíferos/metabolismo
5.
Zhongguo Zhong Yao Za Zhi ; 48(2): 374-381, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36725227

RESUMO

This study aims to screen a strain from Armillaria for the cultivation of Gastrodia elata. Specifically, Armillaria strains were isolated from different producing areas of G. elata and identified. Based on the growth characteristics of the strains and the experiment on the cultivation of G. elata, an optimal A. gallica strain was screened out. The specific process is as follows. The fungus-gro-wing materials of G. elata were collected from four producing areas and the Armillaria strains were isolated(G,Y,S,H). The strains were then identified based on morphological observation and phylogeny analysis and the commonly used strains were determined. The sucrase genotypes of the strains were identified according to our previous research findings, and the growth characteristics of the strains, such as growth rate, diameter, dry weight, and polysaccharide content of the rhizomorphs, were measured. According to the biological characteristics and sucrase genotypes, two strains were selected for the cultivation of G. elata. The tuber yield and the content of gastrodin and p-hydroxybenzyl alcohol in the tuber of G. elata were measured to select the optimal strain. The results showed that the four strains were all A. gallica. The rhizomorphs of strains G and H of the same sucrase genotype had larger/higher length, growth rate, diameter, branch number, dry weight, and polysaccharide content than those of strains S and Y of the same sucrase genotype. The tuber yield and the total content of gastrodin and p-hydroxybenzyl alcohol in tuber of G. elata cultivated with strain H were 6.528 kg·m~(-2) and 0.566%, respectively, which were 4.58 and 1.30 folds those of G. elata cultivated with strain S. Strains H and S were screened out from four strains of A. gallica based on the growth characteristics and sucrase genotype. According to the tuber yield and content of total gastrodin and p-hydroxybenzyl alcohol in the tuber of G. elata, strain H was identified as the optimal one. The findings in this study are expected to lay a basis for cultivating G. elata with high yield and quality of tubers.


Assuntos
Armillaria , Gastrodia , Armillaria/genética , Polissacarídeos
6.
Molecules ; 28(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36677669

RESUMO

Scavenger receptor class B type 1 (SR-B1), a multiligand membrane receptor, is expressed in a gradient along the gastrocolic axis. SR-B1 deficiency enhances lymphocyte proliferation and elevates inflammatory cytokine production in macrophages. However, whether SR-B1 affects intestinal metabolites is unclear. In this study, we detected metabolite changes in the intestinal tissue of SR-B1-/- mice, including amino acids and neurotransmitters, by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) and HPLC. We found that SR-B1-/- mice exhibited changes in intestinal lipid metabolites and metabolic pathways, including the glycerophospholipid, sphingolipid, linoleic acid, taurine, and hypotaurine metabolic pathways. SR-B1 deficiency influenced the contents of amino acids and neurotransmitters in all parts of the intestine; the contents of leucine (LEU), phenylalanine (PHE), tryptophan (TRP), and tyrosine (TYR) were affected in all parts of the intestine; and the contents of 3,4-dihydroxyphenylacetic acid (DOPAC) and dopamine (DA) were significantly decreased in both the colon and rectum. In summary, SR-B1 deficiency regulated intestinal lipids, amino acids, and neurotransmitter metabolism in mice.


Assuntos
Aminoácidos , Intestinos , Camundongos , Animais , Camundongos Knockout , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Cromatografia Líquida de Alta Pressão
7.
J Colloid Interface Sci ; 636: 11-20, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36621125

RESUMO

Efficient and economic bifunctional electrocatalyst for water splitting to produce hydrogen is urgently required. The layered double hydroxides (LDHs) have shown superior activity for oxygen evolution reaction (OER) for water electrolysis, while their hydrogen evolution reaction (HER) activity remains challenging. Herein, we report an alkali hydrothermal-treatment strategy to enhance the HER as well as OER performance of NiCo-LDH. This method can create metal vacancies and newly formed Ni/Co(OH)2 phase over NiCo-LDH, tune the electronic structure, and improve the electrical conductivity, thereby improving the electrochemical activity. The NiCo-LDH-OH catalyst delivers a current density of 10 mA cm-2 at an overpotential of 180 mV for HER and an overpotential of 317 mV for OER, which is greatly reduced compared to the pristine NiCo-LDH (295 mV for HER and 336 mV for OER). When assembled into an electrolyzer both as a cathode and anode, it demonstrates superior activity for overall water splitting with no obvious decay after 20 h. This work paves a new path for fabricating efficient LDHs-based HER/OER bifunctional catalysts.

8.
Phytochemistry ; 207: 113583, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36623702

RESUMO

Chemical constituent investigation on the n-BuOH extract of the rhizomes of Tupistra chinensis Baker leads to the isolation of ten compounds including eight undescribed furostanol saponins, tupischinosides A - H, and two known ones. The structures of isolated compounds were determined by extensive spectral analysis and chemical evidences. Interestingly, tupischinosides A and B, C and D, E and F, G and H were identified as four pairs of epimers. The cytotoxicity of tupischinosides A - H against human cancer cell lines U87, SHG44, U251, LN229 and HepG-2 was evaluated by CCK-8 method. As a result, tupischinosides A and C exhibited significant proliferation inhibitory effect on the tested cancer cells. On the contrary, the corresponding epimers, tupischinosides B and D, which only differ in the configuration of C-23 didn't exhibit any cytotoxicity to cancer cells. These results indicated that the stereochemistry of C-23 was crucial to the activity of the compounds.


Assuntos
Liliaceae , Saponinas , Humanos , Saponinas/farmacologia , Saponinas/química , Rizoma/química , Liliaceae/química , Estrutura Molecular , Linhagem Celular
9.
Inorg Chem ; 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36608341

RESUMO

Radiolanthanides and actinides are aptly suited for the diagnosis and treatment of cancer via nuclear medicine because they possess unique chemical and physical properties (e.g., radioactive decay emissions). These rare radiometals have recently shown the potential to selectively deliver a radiation payload to cancer cells. However, their clinical success is highly dependent on finding a suitable ligand for stable chelation and conjugation to a disease-targeting vector. Currently, the commercially available chelates exploited in the radiopharmaceutical design do not fulfill all of the requirements for nuclear medicine applications, and there is a need to further explore their chemistry to rationally design highly specific chelates. Herein, we describe the rational design and chemical development of a novel decadentate acyclic chelate containing five 1,2-hydroxypyridinones, 3,4,3,3-(LI-1,2-HOPO), referred to herein as HOPO-O10, based on the well-known octadentate ligand 3,4,3-(LI-1,2-HOPO), referred to herein as HOPO-O8, a highly efficient chelator for 89Zr[Zr4+]. Analysis by 1H NMR spectroscopy and mass spectrometry of the La3+ and Tb3+ complexes revealed that HOPO-O10 forms bimetallic complexes compared to HOPO-O8, which only forms monometallic species. The radiolabeling properties of both chelates were screened with [135La]La3+, [155/161Tb]Tb3+, [225Ac]Ac3+ and, [227Th]Th4+. Comparable high specific activity was observed for the [155/161Tb]Tb3+ complexes, outperforming the gold-standard 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, yet HOPO-O10 surpassed HOPO-O8 with higher [227Th]Th4+ affinity and improved complex stability in a human serum challenge assay. A comprehensive analysis of the decadentate and octadentate chelates was performed with density functional theory for the La3+, Ac3+, Eu3+, Tb3+, Lu3+, and Th4+ complexes. The computational simulations demonstrated the enhanced stability of Th4+-HOPO-O10 over Th4+-HOPO-O8. This investigation reveals the potential of HOPO-O10 for the stable chelation of large tetravalent radioactinides for nuclear medicine applications and provides insight for further chelate development.

10.
Langmuir ; 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36628490

RESUMO

Facilitation of the photocarrier separation is a crucial strategy for developing highly efficient photocatalysts in eliminating environmental pollutants. Herein we have developed a new kind of Ag2MoO4/ZnWO4 (AMO/ZWO) composite photocatalysts with a Z-scheme mechanism by anchoring AMO nanoparticles onto ZWO nanorods. Multiple characterization methodologies and density functional theory (DFT) calculations were employed to study the performances of the AMO/ZWO heterojunctions as well as the underlying photocatalytic mechanism. Simulated-sunlight-driven photodegradation experiments for removing methylene blue (MB) demonstrates that the 8%AMO/ZWO heterojunction can photocatalytically remove 99.8% of MB within 60 min, and the reaction rate constant is obtained as 0.10199 min-1, which is enhanced by 6.8 (or 4.9) times when compared with that of pure ZWO (or AMO). On the base of the experimental results and DFT calculations, the enhanced photocatalytic mechanism of the AMO/ZWO heterojunctions was revealed to be the efficient separation of photocarriers via a Z-scheme transfer process. In addition, photodegradion of various organic pollutants over 8%AMO/ZWO was further compared and aimed at incorporating it into industrial application in pollutant removal.

11.
BMC Neurol ; 23(1): 35, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36690929

RESUMO

BACKGROUND: Spinal muscular atrophy (SMA) is a progressive degenerative neuromuscular disease. Nusinersen, with its quick onset of action, can benefit patients early in the treatment course. However, there are currently no clinical studies regarding the improvement in motor function and nutritional status of patients after loading period treatment with nusinersen. Here, we aimed to determine the efficacy of nusinersen in improving motor function and nutritional status in children with SMA treated with nusinersen after loading period in Western China. METHODS: In this retrospective study, data for all pediatric patients (aged < 18 years), with genetically confirmed diagnosis of SMA who were treated with nusinersen, were collected before initiation of treatment and after 2 months of treatment. We assessed motor function using standardized scales and nutritional status of patients with SMA as well as side effects of nusinersen. RESULTS: Forty-six pediatric patients aged < 18 years were enrolled in this study. After 2 months of treatment, the motor function of patients with SMA type 1, 2, and 3 improved. The difference in Revised Upper Limb Module scores from M0 to M2 was significant in patients with SMA type 2 and 3 (P = 0.004, P = 0.042, respectively). The difference in Hammersmith Functional Motor Scale Expanded scores from M0 to M2 in patients with SMA type 2 was also significant (P = 0.000). No significant differences were found for Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorder (CHOP-INTEND), Hammersmith Infant Neurologic Examination-Part 2 (HINE-2), and 6-Minute Walking Test (6MWT) scores between M0 and M2, but the scores of CHOP-INTEND, HINE-2, and 6MWT were all increased after loading period treatment. The overall improvement in nutritional status was not statistically significant. No serious adverse effects were observed. CONCLUSIONS: Our study provides evidence for the efficacy and safety of nusinersen and the nutritional status of pediatric patients with SMA after the loading period treatment. Motor function of all patients improved after 2 months of loading period nusinersen treatment. Patients with a shorter disease duration showed better response to treatment. Careful surveillance of nutritional status is needed in patients with SMA.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Atrofia Muscular Espinal , Atrofias Musculares Espinais da Infância , Lactente , Criança , Humanos , Estudos Retrospectivos , Oligonucleotídeos/farmacologia , Oligonucleotídeos/uso terapêutico , China
12.
Chemphyschem ; : e202200657, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36646629

RESUMO

The discovery of high-performance catalysts for the electrochemical CO2 reduction reaction (CO2 RR) has faced an enormous challenge for years. The lack of cognition about the surface active structures or centers of catalysts in complex conditions limits the development of advanced catalysts for CO2 RR. Recently, the positive valent metal sites (PVMS) are demonstrated as a kind of potential active sites, which can facilitate carbon dioxide (CO2 ) activation and conversation but are always unstable under reduction potentials. Many advanced technologies in theory and experiment have been utilized to understand and develop excellent catalysts with PVMS for CO2 RR. Here, we present an introduction of some typical catalysts with PVMS in CO2 RR and give some understanding of the activity and stability for these related catalysts.

13.
J Food Sci ; 88(1): 204-213, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36533938

RESUMO

Crystal malt, the most popular type of specialty malt used in beer brewing, plays a vital role in forming complex flavor and color. Nevertheless, crystal malt is only defined based on the malting process, and there is not any standard to evaluate its quality. In the current study, the volatile aroma constituents of commercial crystal malt samples were analyzed with headspace solid-phase microextraction combined with gas chromatography-mass spectrometry, in order to explore the characteristic aroma compounds of crystal malt. The average concentration of volatile aroma compounds in 10 crystal malt samples is 587 µg L-1 , ranging from 347 to 1265 µg L-1 . A total of 38 aroma compounds were identified, 47% of which were existed in all the 10 samples. Based on principal component analysis and odor activity value, isobutyraldehyde, 2-methylbutanal, furfural, 2-acetyl-1H-pyrrole, oct-1-en-3-ol, 4-methyl-2-phenyl-2-pentenal, and (2E)-2-isopropyl-5-methyl-2-hexenal could be considered the characteristic aroma compounds of crystal malt. The results of this present study would help to establish a standard to assess the quality traits of crystal malt sample.


Assuntos
Odorantes , Compostos Orgânicos Voláteis , Odorantes/análise , Compostos Orgânicos Voláteis/análise , Cromatografia Gasosa-Espectrometria de Massas , Plântula/química , Microextração em Fase Sólida/métodos
14.
Cell Metab ; 35(1): 101-117.e11, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36525963

RESUMO

sn-1,2-diacylglycerol (sn-1,2-DAG)-mediated activation of protein kinase Cε (PKCε) is a key pathway that is responsible for obesity-related lipid metabolism disorders, which induces hepatic insulin resistance and type 2 diabetes. No small molecules have been previously reported to ameliorate these diseases through this pathway. Here, we screened and identified the phytochemical atractylenolide II (AT II) that reduces the hepatic sn-1,2-DAG levels, deactivates PKCε activity, and improves obesity-induced hyperlipidemia, hepatosteatosis, and insulin resistance. Furthermore, using the ABPP strategy, the diacylglycerol kinase family member DGKQ was identified as a direct target of AT II. AT II may act on a novel drug-binding pocket in the CRD and PH domains of DGKQ to thereby allosterically regulate its kinase activity. Moreover, AT II also increases weight loss by activating DGKQ-AMPK-PGC1α-UCP-1 signaling in adipose tissue. These findings suggest that AT II is a promising lead compound to improve obesity-induced insulin resistance.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Proteína Quinase C-épsilon/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diglicerídeos/metabolismo , Obesidade/tratamento farmacológico
15.
Theriogenology ; 197: 198-208, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36525859

RESUMO

Activin/inhibin is an important factor for the fecundity of Hu sheep, and it is involved in follicular development in ovaries. Inhibin subunit beta A (INHBA) participates in the synthesis of activin A and inhibin A. In this study, we also noted a positive correlation between INHBA level and the secretion of both activin A and inhibin A in culture medium. Nevertheless, both knockdown and overexpression of INHBA downregulated the expression of Inhibin Subunit Alpha (INHA). Based on RNA-Sequencing, we further examined the effect and molecular mechanism of INHBA knockdown in GCs on mRNA expression. A total of 1,687 differentially expressed genes (DEGs) were identified (Fold change ≥ 2; False-discovory-rates (FDR) ≤ 0.01), of which 602 genes were upregulated and 1,087 genes were downregulated in the INHBA interference group compared with the control groups. Gene Ontology (GO) enrichment indicated that these DEGs were mainly involved in the regulation of cell cycle, protein serine/threonine kinase activity, and actin cytoskeleton reorganization. Moreover, DEGs were significantly enriched in 40 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including P53, progesterone-mediated oocyte maturation, and PI3K-AKT signaling pathways. We also noted a positive correlation between INHBA level and many PI3K/Akt/mTOR pathway-related genes at the gene or/and protein expression. Overall, this study may contribute to a better understanding of the roles of INHBA on GCs of prolific sheep, as well as the molecular effect of low INHBA expression on GCs, clarifying some reproductive failures.


Assuntos
Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Feminino , Animais , Ovinos/genética , RNA-Seq/veterinária , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Inibinas/metabolismo , Células da Granulosa/fisiologia
16.
Appl Immunohistochem Mol Morphol ; 31(1): 57-63, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36121292

RESUMO

Osteoarthritis (OA) is the main joint disease associated with aging. Previous studies have confirmed that both osteopontin (OPN) and αvß3 integrin are involved in the progression of knee OA. The purpose of this study was to determine the expression of OPN and αvß3 integrin and chondrocyte senescence levels in OA. Forty-six cartilage tissues from normal and knee OA patients were divided into 4 groups of normal, minor, moderate, and severe lesions based on the Mankin score. Immunohistochemistry and western blotting were used to determine the expression of αvß3, OPN, and senescent-associated-ß-galactosidase (SAß-gal) in articular cartilage. Then, Spearman's correlation was used to analyze the correlations between the Mankin scores and αvß3, OPN and SAß-gal. Pearson correlation analysis was used to analyze the correlations among αvß3, OPN, and SAß-gal. The expression of OPN, αvß3, and SAß-gal in articular cartilage was explored. αvß3, OPN, and SAß-gal proteins were all elevated in OA cartilage, and the correlation coefficient between the Mankin score and the average optical density value of αvß3, OPN, SAß-gal were r =0.60, r =0.75, and r =0.87, respectively, all P <0.001; the correlation between the average optical density value of αvß3 and OPN was r =0.3191, P <0.05; the correlation between αvß3 and SAß-gal was r =0.4955, P <0.001; and the correlation between OPN and SAß-gal was r =0.7821, P <0.001. The correlations among αvß3, OPN, and SAß-gal expression in articular cartilage might be important in OA progression and pathogenesis. Nonetheless, more research is needed to elucidate the exact contribution of αvß3, OPN, and SAß-gal to the degenerative process of OA.


Assuntos
Cartilagem , Condrócitos , Integrina alfaVbeta3 , Osteopontina , Humanos , Gravidade do Paciente , Integrina alfaVbeta3/metabolismo , Condrócitos/citologia , Senescência Celular
17.
J Microbiol Biotechnol ; 33(1): 43-50, 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36517045

RESUMO

Fungal keratitis is a refractory kind of keratopathy. We attempted to investigate the anti-inflammatory role of thymol on Aspergillus fumigatus (A. fumigatus) keratitis. Wound healing and fluorescein staining of the cornea were applied to verify thymol's safety. Mice models of A. fumigatus keratitis underwent subconjunctival injection of thymol. The anti-inflammatory roles of thymol were verified by hematoxylin-eosin (HE) staining, slit lamp observation, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. In contrast with the DMSO group, more transparent corneas and less inflammatory cells infiltration were detected in mice treated with 50 µg/ml thymol. Thymol downregulated the synthesis of TLR4, MyD88, NF-kB, IL-1ß, NLRP3, caspase 1, caspase 8, GSDMD, RIPK3 and MLKL. In summary, we proved that thymol played a protective part in A. fumigatus keratitis by cutting down inflammatory cells aggregation, downregulating the TLR4/ MyD88/ NF-kB/ IL-1ß signal expression and reducing necroptosis and pyroptosis.


Assuntos
Aspergilose , Ceratite , Animais , Camundongos , Aspergillus fumigatus/genética , Aspergillus fumigatus/metabolismo , Timol/farmacologia , Timol/uso terapêutico , NF-kappa B/genética , NF-kappa B/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Aspergilose/tratamento farmacológico , Aspergilose/metabolismo , Piroptose , Necroptose , Ceratite/tratamento farmacológico , Ceratite/metabolismo , Ceratite/microbiologia , Anti-Inflamatórios/uso terapêutico , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
18.
Cytokine ; 162: 156112, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36521238

RESUMO

PURPOSE: Atractylenolide I (AT-I) is a natural sesquiterpene with anti-inflammatory effects. The purpose of this study was to research the anti-inflammatory effect of AT-I on Aspergillus fumigatus(A. fumigatus) keratitis in mice. METHODS: Cytotoxicity test and cell scratch test were used to determine the therapeutic concentrations of corneal infections. In vivo and in vitro studies, mouse cornea and human corneal epithelial cells (HCECs) infected with A. fumigatus were treated with AT-I or dimethyl sulfoxide (DMSO). Then, to analyze the effect of AT-I on inflammatory response, namely neutrophil or macrophage recruitment and the expression of cytokines involving MyD88, NF-κB, interleukin 1ß (IL-1ß) and interleukin 10 (IL-10). To study the effects of the drug, the techniques used include slit-lamp photography, immunofluorescence, myeloperoxidase (MPO) detection, quantitative real-time polymerase chain reaction (QRT-PCR), and western blot. At the same time, in order to explore the combined effect of the drug and natamycin, slit-lamp photographs and clinical scores were used to visually display the disease process. RESULTS: No cytotoxicity was observed under the action of AT-I at a concentration of 800 µM. In mouse models, AT-I significantly suppressed inflammatory responses, reduced neutrophil and macrophage recruitment, and decreased myeloperoxidase levels early in infection. Studies have shown that AT-I may reduce the levels of IL-1ß and IL-10 by inhibiting the MyD88/ NF-κB pathway. The drug combined with natamycin can increase corneal transparency in infected mice. CONCLUSION: AT-I may inhibit MyD88 / NF-κB pathway and the secretion of inflammatory factors IL-1 ß and IL-10 to achieve the therapeutic effect of fungal keratitis.


Assuntos
Aspergilose , Ceratite , Sesquiterpenos , Humanos , Animais , Camundongos , Aspergillus fumigatus , Interleucina-10/metabolismo , NF-kappa B/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Interleucina-1beta/metabolismo , Peroxidase/metabolismo , Natamicina/uso terapêutico , Aspergilose/tratamento farmacológico , Ceratite/tratamento farmacológico , Ceratite/metabolismo , Ceratite/microbiologia , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêutico , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Camundongos Endogâmicos C57BL
19.
Spectrochim Acta A Mol Biomol Spectrosc ; 289: 122228, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36516589

RESUMO

The abuse of pesticides, antibiotics, organic solvents, etc., not only deteriorates the ecological environment, but even affects the normal development of organisms, posing a serious threat to global public health.Efficient and sensitive detection of pesticides, antibiotics, organic solvents and so on are very important, but also a challenge to scientists. By depositing Ag nanoparticles on the surface of Zn-MOF (1: {[Zn2(bta)(bpy)(H2O)2]·2H2O}n), a new type of composite material (Ag@1) was successfully synthesized and analyzed by TEM, EDS, XPS, XRD, IR and other characterization methods. Ag@1 can serve as multi-response fluorescence sensor to detect pesticides (fluazinam (FLU) and emamectin benzoate (EMB)), Tryptophan (Trp) and Ethylenediamine (EDA). In particular, Ag@1 showed "turn-off" fluorescence sensing for FLU and EDA, and "turn-on" fluorescence sensing for EMB and Trp. It is worth mentioning that we further explored its analysis of FLU and Trp in real water samples and fetal bovine serum. The recoveries are satisfactory, 97.95 % - 102.39 % and 96.69 % - 101.85 %, respectively. In addition, the photocatalytic performance of Ag@1 was found to be excellent, the degradation rate of methylene blue (MB) reached 86 %, and its degradation mechanism was discussed.


Assuntos
Nanopartículas Metálicas , Praguicidas , Prata , Triptofano , Fluorescência , Antibacterianos , Corantes , Etilenodiaminas , Solventes , Zinco
20.
J Hum Kinet ; 84: 32-42, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36457478

RESUMO

Prolonged overactivity of the upper trapezius muscle with myofascial trigger points might cause muscle fatigue and subsequently change scapular kinematics and associated muscular activities. Scapular kinematics and associated muscular activities were investigated in 17 overhead athletes with upper trapezius myofascial trigger points and 17 controls before and after a fatigue task. Participants performed a fatigue task requiring sustained isometric scapular elevation. The outcomes included scapular kinematics (upward/downward rotation, external/internal rotation, posterior/anterior tilt) that were tracked by the Polhemus FASTRAK (Polhemus Inc., Colchester, VT, USA) system with Motion Monitor software and muscular activities (upper trapezius, lower trapezius and serratus anterior) that were collected at 1000 Hz per channel using a 16-bit analog-to-digital converter (Model MP 150, Biopac systems Inc., CA, USA) with pairs of silver chloride circular surface electrodes (The Ludlow Company LP, Chocopee, MA) during arm elevation. Mixed ANOVAs were conducted to characterize the outcomes with and without a fatigue task in participants with myofascial trigger points. Decreased scapular posterior tipping during 90 degrees of arm raising/lowering (effect sizes of 0.51 and 0.59) was likely to be elicited by the scapular elevation fatigue task in the presence of myofascial trigger points. Activity of the lower trapezius was higher in the myofascial trigger point group (6.2%, p = 0.036) than in the control group. Following the fatigue task, both groups showed increased activity in the upper trapezius (9.0%, p = 0.009) during arm lowering and in the lower trapezius (2.7%, p < 0.01) during arm raising and lowering. Decreased scapular posterior tipping during 90 degrees of arm raising/lowering after a fatigue task may lead to impingement. We found that the presence of upper trapezius myofascial trigger points in amateur overhead athletes was related to impaired scapular kinematics and associated muscular activities during arm elevation after a fatigue task, especially the decreased scapular tipping during 90 degrees of raising/lowering.

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