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1.
J Mater Sci Mater Med ; 35(1): 22, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526601

RESUMO

Biodegradable porous Mg scaffolds are a promising approach to bone repair. In this work, 3D-spherical porous Mg-1.5Zn-0.2Ca (wt.%) scaffolds were prepared by vacuum infiltration casting technology, and MgF2 and fluorapatite coatings were designed to control the degradation behavior of Mg-based scaffolds. The results showed that the pores in Mg-based scaffolds were composed of the main spherical pores (450-600 µm) and interconnected pores (150-200 µm), and the porosity was up to 74.97%. Mg-based porous scaffolds exhibited sufficient mechanical properties with a compressive yield strength of about 4.04 MPa and elastic modulus of appropriately 0.23 GPa. Besides, both MgF2 coating and fluorapatite coating could effectively improve the corrosion resistance of porous Mg-based scaffolds. In conclusion, this research would provide data support and theoretical guidance for the application of biodegradable porous Mg-based scaffolds in bone tissue engineering.


Assuntos
Procedimentos de Cirurgia Plástica , Porosidade , Apatitas , Zinco
2.
Virology ; 593: 109999, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38368638

RESUMO

We report the discovery and characterization of a novel adenovirus, Zoothera dauma adenovirus (ZdAdV), from a wild bird species, Zoothera dauma (Scaly thrush). This new atadenovirus was discovered by metagenomic sequencing without virus cultivation. Analyses of the full genome sequence revealed that this new virus is a distinct member of the genus Atadenovirus and represents a novel species. ZdAdV has a genome of 34,760 bp with 28 predicted genes and 39% GC content. ZdAdV is the first atadenovirus to contain ORF19, a gene previously found only in aviadenoviruses. Phylogenetic analysis of ORF19 suggests that it was acquired by ZdAdV through horizontal gene transfer from an aviadenovirus. By analyzing all orthologous genes of aviadenovirus, mastadenovirus, atadenovirus, and siadenovirus, we also found potential horizontal gene transfer for the E4 gene in Pigeon aviadenovirus B. Our study widens our knowledge concerning the genetic diversity and evolutionary history of atadenoviruses and their potential for cross-species transmission.


Assuntos
Infecções por Adenoviridae , Atadenovirus , Aviadenovirus , Animais , Atadenovirus/genética , Genoma Viral , Filogenia , Transferência Genética Horizontal , Adenoviridae/genética , Aviadenovirus/genética , Aves , Infecções por Adenoviridae/genética
3.
Front Endocrinol (Lausanne) ; 14: 1270145, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38027131

RESUMO

Diabetic retinopathy (DR) is a prevalent complication of diabetes, significantly impacting patients' quality of life due to vision loss. No pharmacological therapies are currently approved for DR, excepted the drugs to treat diabetic macular edema such as the anti-VEGF agents or steroids administered by intraocular route. Advancements in research have highlighted the crucial role of early intervention in DR for halting or delaying disease progression. This holds immense significance in enhancing patients' quality of life and alleviating the societal burden associated with medical care costs. The non-proliferative stage represents the early phase of DR. In comparison to the proliferative stage, pathological changes primarily manifest as microangiomas and hemorrhages, while at the cellular level, there is a loss of pericytes, neuronal cell death, and disruption of components and functionality within the retinal neuronal vascular unit encompassing pericytes and neurons. Both neurodegenerative and microvascular abnormalities manifest in the early stages of DR. Therefore, our focus lies on the non-proliferative stage of DR and we have initially summarized the mechanisms involved in its development, including pathways such as polyols, that revolve around the pathological changes occurring during this early stage. We also integrate cutting-edge mechanisms, including leukocyte adhesion, neutrophil extracellular traps, multiple RNA regulation, microorganisms, cell death (ferroptosis and pyroptosis), and other related mechanisms. The current status of drug therapy for early-stage DR is also discussed to provide insights for the development of pharmaceutical interventions targeting the early treatment of DR.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/etiologia , Retinopatia Diabética/metabolismo , Qualidade de Vida , Edema Macular/complicações , Neurônios/metabolismo , Pericitos/metabolismo
4.
Artigo em Chinês | MEDLINE | ID: mdl-37828884

RESUMO

Objective:To study the application value of narrow-band imaging in the diagnosis of laryngopharyngeal reflux. Methods:A total of 275 patients admitted to the inpatient department or laryngoscopy room of the Otolaryngology Head and Neck Surgery Department of the First Affiliated Hospital of Harbin Medical University from September 2022 to April 2023 due to throat discomfort were selected as the research subjects. All of them completed RSI, RFS scoring scales and electronic laryngoscopy(including ordinary white light and NBI). According to the expert consensus of LPRD in 2022, RSI and RFS scoring scale were used as diagnostic criteria to divide them into LPR group and non-LPR group. Chi-square test was used to analyze the differences of positive rates of characteristic manifestations under NBI among different groups. The consistency of NBI and scale diagnostic methods was analyzed by Kappa, and RSI and RFS scoring were used as diagnostic criteria, The diagnostic efficiency of NBI method was analyzed. Results:There were 190 people in the LPR group, 157 of whom showed characteristic performance under the NBI mode, with a positive rate of 82.6%(157/190); there were 85 people in the non-LPR group, with a positive rate of 18.8%(16/85). There was a statistically significant difference in the positive rate between the two groups(χ²=102.47, P<0.05). The consistency rate between RSI, RFS and NBI was 82.2%(226/275). Kappa consistency analysis was used, and Kappa=0.605(P<0.05), indicating good consistency between the two diagnostic methods. Using RSI and RFS as diagnostic criteria for LPR, the sensitivity of NBI diagnostic method was 82.6%(157/190), specificity 81.2%(69/85), positive predictive value 90.8%(157/173) and negative predictive value 67.6%(69/102). Conclusion:Narrow-band imaging, as a new endoscopic imaging technique, can show small changes in mucosal surface micro vessels and play an important role in the diagnosis of laryngopharyngeal reflux.


Assuntos
Refluxo Laringofaríngeo , Humanos , Refluxo Laringofaríngeo/diagnóstico por imagem , Imagem de Banda Estreita , Laringoscopia/métodos , Faringe , Valor Preditivo dos Testes
5.
Biochim Biophys Acta Gene Regul Mech ; 1866(4): 194967, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37553065

RESUMO

The N6-methyladenosine (m6A) modification is regulated by methylases, commonly referred to as "writers," and demethylases, known as "erasers," leading to a dynamic and reversible process. Changes in m6A levels have been implicated in a wide range of cellular processes, including nuclear RNA export, mRNA metabolism, protein translation, and RNA splicing, establishing a strong correlation with various diseases. Both physiologically and pathologically, m6A methylation plays a critical role in the initiation and progression of kidney disease. The methylation of m6A may also facilitate the early diagnosis and treatment of kidney diseases, according to accumulating research. This review aims to provide a comprehensive overview of the potential role and mechanism of m6A methylation in kidney diseases, as well as its potential application in the treatment of such diseases. There will be a thorough examination of m6A methylation mechanisms, paying particular attention to the interplay between m6A writers, m6A erasers, and m6A readers. Furthermore, this paper will elucidate the interplay between various kidney diseases and m6A methylation, summarize the expression patterns of m6A in pathological kidney tissues, and discuss the potential therapeutic benefits of targeting m6A in the context of kidney diseases.


Assuntos
Nefropatias , Metiltransferases , Humanos , Metilação , Metiltransferases/genética , RNA , Adenosina , Nefropatias/genética , Nefropatias/terapia
6.
Int J Oncol ; 63(4)2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37594084

RESUMO

Following the publication of the above article, a concerned reader drew to the Editor's attention that, for the Transwell invasion and migration assay experiments shown in Figs. 5 and 6, there were multiple instances of apparently overlapping data panels, such that the data would have been derived from the same original sources where they were intended to show the results from differently performed experiments; moreover, certain of the data shown in Fig. 5B were strikingly similar to data that had appeared in Fig. 2 in a previously published paper written by different authors at different research institutes [Tian F, Ding D and Li D: Fangchinoline targets PI3K and suppresses PI3K/AKT signaling pathway in SGC7901 cells. Int J Oncol 46: 2355­2363, 2015]. In view of the fact that certain of the data in the above article had already appeared in a previously published paper, and given the large number of apparently overlapping data panels identified in the two referenced figures, the Editor of International Journal of Oncology has decided that this paper should be retracted from the publication. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 50: 1590­1600, 2017; DOI: 10.3892/ijo.2017.3928].

7.
Sci Rep ; 13(1): 14048, 2023 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-37640759

RESUMO

Platycodon grandiflorum (Jacq.) A. DC. has been proposed as a medicine and food homology, thus playing an important role in disease prevention and health promotion, with great potential for research and value in clinical application. We aimed to analyze stakeholders' production behavior and financial performance from a value chain (VC) perspective and provide a basis for improving the quality of P. grandiflorum and the interests of stakeholders. P. grandiflorum collected from different producing areas were chemically analyzed, and the quality of platycodin D was evaluated. Rstudio3.6.0 was used to analyze the correlation between total platycodins (as platycodin D, platycoside E, and platycodin D3) and platycodin D in P. grandiflorum, providing the basis for quality control of P. grandiflorum. In addition, we studied the anti-inflammatory and anti-cancer activities of P. grandiflorum extract under different links. Based on the food chain energy pyramid, the transfer efficiency of active components of P. grandiflorum in different links was studied. Accordingly, 10 different types of VCs were determined in producing P. grandiflorum. Our results show that vertical coordination has led to a more consistent traceability system and strict regulation of supply chains.


Assuntos
Platycodon , Cadeia Alimentar , Controle de Qualidade , Alimentos
8.
Clin Immunol ; 254: 109698, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37481013

RESUMO

Strengthened glycolysis is crucial for the macrophage pro-inflammatory response during sepsis. Activating transcription factor 4 (ATF4) plays an important role in regulating glucose and lipid metabolic homeostasis in hepatocytes and adipocytes. However, its immunometabolic role in macrophage during sepsis remains largely unknown. In the present study, we found that the expression of ATF4 in peripheral blood mononuclear cells (PBMCs) was increased and associated with glucose metabolism in septic patients. Atf4 knockdown specifically decreased LPS-induced spleen macrophages and serum pro-inflammatory cytokines levels in mice. Moreover, Atf4 knockdown partially blocked LPS-induced pro-inflammatory cytokines, lactate accumulation and glycolytic capacity in RAW264.7. Mechanically, ATF4 binds to the promoter region of hexokinase II (HK2), and interacts with hypoxia inducible factor-1α (HIF-1α) and stabilizes HIF-1α through ubiquitination modification in response to LPS. Furthermore, ATF4-HIF-1α-HK2-glycolysis axis launches pro-inflammatory response in macrophage depending on the activation of mammalian target of rapamycin (mTOR). Importantly, Atf4 overexpression improves the decreased level of pro-inflammatory cytokines and lactate secretion and HK2 expression in LPS-induced tolerant macrophages. In conclusion, we propose a novel function of ATF4 as a crucial glycolytic activator contributing to pro-inflammatory response and improving immune tolerant in macrophage involved in sepsis. So, ATF4 could be a potential new target for immunotherapy of sepsis.


Assuntos
Hexoquinase , Sepse , Animais , Camundongos , Fator 4 Ativador da Transcrição/metabolismo , Citocinas/metabolismo , Glicólise , Hexoquinase/genética , Hexoquinase/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Tolerância Imunológica , Ácido Láctico , Leucócitos Mononucleares/metabolismo , Lipopolissacarídeos , Macrófagos/metabolismo , Mamíferos/metabolismo , Sepse/genética , Sepse/metabolismo , Ubiquitinação
9.
Biomed Res Int ; 2023: 4444869, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36814797

RESUMO

Background: Lysine crotonylation (Kcr) is a newly identified posttranslational modification type regulated by various enzymes and coenzymes, including lysine crotonyltransferase, lysine decrotonylase, and binding proteins. However, the role of Kcr regulators in head and neck squamous cell carcinoma (HNSCC) remains unknown. The aim of this study was to establish and validate a Kcr-related prognostic signature of HNSCC and to assess the clinical predictive value of this signature. Methods: The mRNA expression profiles and clinicopathological data from The Cancer Genome Atlas (TCGA) database were downloaded to explore the clinical significance and prognostic value of these regulators in HNSCC. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to generate the Kcr-related prognostic signature for HNSCC. Subsequently, the GSE65858 dataset from the Gene Expression Omnibus (GEO) database was used to validate the signature. The prognostic value of the signature was evaluated using the Kaplan-Meier survival, receiver operating characteristic (ROC) curve, and univariate and multivariate Cox regression analyses. Results: We established a nine-gene risk signature associated with the prognosis of HNSCC based on Kcr regulators. High-risk patients demonstrated significantly poorer overall survival (OS) than low-risk patients in the training (TCGA) and validation (GEO) datasets. Then, the time-dependent receiver operating characteristic (ROC) curve analysis showed that the nine-gene risk signature was more accurate for predicting the 5-year OS than other clinical parameters, including age, gender, T stage, N stage, and histologic grade in the TCGA and GEO datasets. Moreover, the Cox regression analysis showed that the constructed risk signature was an independent risk factor for HNSCC. Conclusion: Our study identified and validated a nine-gene signature for HNSCC based on Kcr regulators. These results might contribute to prognosis stratification and treatment escalation for HNSCC patients.


Assuntos
Neoplasias de Cabeça e Pescoço , Lisina , Humanos , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Relevância Clínica
10.
Arch Virol ; 168(2): 68, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36656447

RESUMO

We present the complete genome sequence of an aviadenovirus obtained by metagenomics from cloacal swabs taken from a free-living Eurasian scops owl (Otus scops, a small raptor distributed in Europe and several parts of Asia) in China. Thirty protein coding genes were predicted in this 40,239-bp-long genome, which encodes the largest fiber protein among all reported aviadenoviruses. The viral genome sequence is highly divergent, and the encoded proteins have an average of only 55% amino acid sequence identity to those of other adenoviruses. In phylogenetic analysis, the new owl virus grouped with members of the genus Aviadenovirus and formed a common clade with another owl adenovirus reported previously in Japan. This is the second complete genome sequence of an aviadenovirus discovered in owls, and its proteins have an average of 62% amino acid sequence identity to those of the previously reported owl adenovirus. Combining this result with comparative genomic analysis of all aviadenoviruses, we propose that this owl virus and the previously described Japanese owl adenovirus can be assigned to two new species in the genus Aviadenovirus. This study provides new data on the diversity of aviadenoviruses in wild birds.


Assuntos
Infecções por Adenoviridae , Aviadenovirus , Estrigiformes , Animais , Adenoviridae/genética , Aviadenovirus/genética , Filogenia , Genoma Viral , Infecções por Adenoviridae/veterinária
11.
Plant Dis ; 107(6): 1874-1882, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36480731

RESUMO

Cherry tomatoes (Solanum lycopersicum) are becoming increasingly popular due to their nutrition and delicious flavor. However, cherry tomatoes are highly perishable and susceptible to various pathogenic microorganisms after harvest, such as Botrytis cinerea. In the pretest experiment, we screened out three kinds of plant essential oils (EOs) (Torreya grandis oil, Eriobotrya japonica oil, and Citrus medica oil) that have strong fungicidal activity on B. cinerea from cherry tomatoes. To further evaluate the postharvest preservation application prospect of these three oils for cherry tomatoes, the oils were extracted from different parts of three plants by hydrodistillation, and their chemical constituents were analyzed by gas chromatography-mass spectrometry. The main representative components of T. grandis oil, E. japonica oil, and C. medica oil were δ-cadinene (11.76%), transnerolidol (9.70%), and 5,7-dimethoxycoumarin (23.22%), respectively. These three EOs effectively inhibited the mycelial growth of B. cinerea in vitro, with EC50 values of 81.672, 144.046, and 221.500 µl/liter, respectively. Compared with the blank control and other oil treatments, the T. grandis oil (at a concentration of 200 µl/liter) fumigation treatment was more effective at inhibiting the growth rate of the pathogen. In addition, the phenolic content and phenylalanine ammonia lyase, ß-1,3-glucanase, chitinase, and peroxidase activities of tomatoes significantly increased on the seventh day due to the T. grandis oil treatment. The present study shows that these three oils with high extraction rates have preservation potential for cherry tomatoes. Among these three EOs, T. grandis oil can be used to further develop preservative products as a fumigant.


Assuntos
Botrytis , Óleos Voláteis , Solanum lycopersicum , Frutas/química , Fumigação , Óleos Voláteis/farmacologia
12.
Ear Hear ; 44(2): 254-263, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36126187

RESUMO

OBJECTIVES: To investigate the value of using the Gesell Development Diagnosis Scale (GDDS) to predict developmental outcomes in very young children who undergo simultaneous bilateral cochlear implantation. DESIGN: In this prospective cohort study, a repeated-measures investigation was conducted in a tertiary referral hospital. A total of 62 children receiving simultaneous bilateral cochlear implantations were enrolled from April 2017 to August 2018. They were divided into 2 groups depending on the operative age: "Infants" group (6 to 12 months, N = 38) or "Children" group (12 to 36 months, N = 24). Data on the surgical outcomes, auditory development, speech production, and developmental indicators were collected until 2 years after the initial fitting. The primary outcome measure was the GDDS, a neuropsychological development examination. Secondary outcomes included the following: complication rate, aided pure-tone average, Infant-Toddler Meaningful Auditory Integration Scale, Categories of Auditory Performance-II, Meaningful Use of Speech Scale, Speech Intelligibility Rating, and the LittlEARS Auditory Questionnaire. RESULTS: The mean ages at implantation in infants and children groups were 9.2 ± 1.17 and 16.6 ± 3.60 months, respectively. Significant differences were found in the social skills ( p = 0.001) and adaptability ( p = 0.031) domains of GDDS. The younger the age of bilateral cochlear implants surgery, the higher developmental quotient of language, social skills, and adaptability the child could achieve after 2 years. The complication rates in the infants and children groups were 0% versus 2.1% ( p = 0.57). There was no surgical complication in the infants group. In the children group, 1 case with enlarged vestibular aqueduct and Mondini malformation had a receiver-implant misplacement on the right side (2%, 1/48). In the two groups, auditory performance and speech production had improved similarly. In the infants group, social skills developmental quotient at baseline had a significant positive relationship with Meaningful Use of Speech Scale after 2 years. CONCLUSIONS: Simultaneous bilateral cochlear implantation in younger children improves adaptability and social skills. GDDS is a sensitive tool of evaluating short-term effect of bilateral cochlear implants in neuropsychological development and constitutes a reliable predictor of speech production for the very younger pediatric cochlear implant users.


Assuntos
Implante Coclear , Implantes Cocleares , Surdez , Perda Auditiva Neurossensorial , Percepção da Fala , Lactente , Criança , Humanos , Pré-Escolar , Estudos Prospectivos , Habilidades Sociais , Perda Auditiva Neurossensorial/cirurgia , Inteligibilidade da Fala , Resultado do Tratamento , Surdez/cirurgia
13.
Anal Chem ; 94(33): 11492-11499, 2022 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-35938925

RESUMO

FcγRIIIa-binding affinity is one of the key factors to ensure the efficacy of many antitumor therapeutic antibodies, which should be monitored along with the titer, protein aggregation, and other critical quality attributes. The conventional workflow for the quality assessment of therapeutic antibodies in harvested cell culture fluid (HCCF) is time-consuming and costly nevertheless. In this study, a tractable method was established for rapid quality assessment of a HCCF sample through differentially extracting IgG with different FcγRIIIa affinity levels using FcγRIIIa-immobilized magnetic microspheres, followed by size exclusion chromatography (SEC) to determine the amount and monomer percentage of IgGs in the preceding eluate. FcγRIIIa-immobilized magnetic microspheres with polydopamine (PDA) and hydrophilic dendrimer (PAMAM) coating (denoted as Fe3O4@PDA@PAMAM-FcγRIIIa) were synthesized for the first time as magnetic adsorbents. The PDA cladding endowed the composites with good chemical stability in acidic elution buffer, and the PAMAM dendrimer empowered the composites of high ligand immobilization capacity and hydrophilic surface. The labile FcγRIIIa was immobilized under mild conditions. By directly applying a simple magnetic solid phase extraction procedure to treat HCCF, favored IgG species with high FcγRIIIa affinity would be selectively captured by Fe3O4@PDA@PAMAM-FcγRIIIa composites for subsequent SEC analysis. The monomer peak area value in SEC, which was set as the read-out of the proposed method, correlated directly with the theoretical overall quality of standard-spiked HCCF samples.


Assuntos
Fenômenos Magnéticos , Magnetismo , Técnicas de Cultura de Células , Imunoglobulina G , Microesferas
14.
Front Genet ; 13: 880945, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35664306

RESUMO

Background: The immune system plays a crucial role in rectal adenocarcinoma (READ). Immune-related genes may help predict READ prognoses. Methods: The Cancer Genome Atlas dataset and GSE56699 were used as the training and validation datasets, respectively, and differentially expressed genes (DEGs) were identified. The optimal DEG combination was determined, and the prognostic risk model was constructed. The correlation between optimal DEGs and immune infiltrating cells was evaluated. Results: Nine DEGs were selected for analysis. Moreover, ADAMDEC1 showed a positive correlation with six immune infiltrates, most notably with B cells and dendritic cells. F13A1 was also positively correlated with six immune infiltrates, particularly macrophage and dendritic cells, whereas LGALS9C was negatively correlated with all immune infiltrates except B cells. Additionally, the prognostic risk model was strongly correlated with the actual situation. We retained only three prognosis risk factors: age, pathologic stage, and prognostic risk model. The stratified analysis revealed that lower ages and pathologic stages have a better prognosis with READ. Age and mRNA prognostic factors were the most important factors in determining the possibility of 3- and 5-year survival. Conclusion: In summary, we identified a nine-gene prognosis risk model that is applicable to the treatment of READ. Altogether, characteristics such as the gene signature and age have a strong predictive value for prognosis risk.

15.
Virus Res ; 317: 198799, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35537575

RESUMO

We present the first complete genome sequence of an aviadenovirus Oriolus adenovirus (OrAdV) sequenced from the cloaca of a Oriolus chinensis (a passerine bird widely distributed in Asia), which was collected from an island off the east coast of China. Thirty-one protein coding genes were predicted in this 40425-bp-long genome. OrAdV genome is highly divergent and has only 57% average protein identity compared with other aviadenovirus genomes. Comparative genomic analysis indicates that this passerine virus is a new species of aviadenovirus. One unique thymidylate kinase gene was discovered in OrAdV genome. This gene is absent in other adenovirus genomes and usually reported to occur in herpesvirus. Protein sequence alignment against all known proteins indicates that this gene may be originated from ancient horizontal gene transfer event between virus and parasitic eukaryote like protozoan. This new aviadenovirus genome enriches the genomic information of adenovirus and suggests that there is a large unknown space of adenovirus world.


Assuntos
Infecções por Adenoviridae , Aviadenovirus , Passeriformes , Adenoviridae/genética , Animais , Aviadenovirus/genética , Genoma Viral , Passeriformes/genética , Filogenia
16.
J Int Med Res ; 50(1): 3000605211067921, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35098772

RESUMO

OBJECTIVE: To investigate the anti-cancer effects and potential mechanisms of eupalinilide B in laryngeal cancer cells. METHODS: Laryngeal cancer cell lines were selected to study the anti-tumor effects of eupalinilide B in vitro and in vivo. Lysine-specific demethylase 1 (LSD1) activity was assessed in vitro and dialysis experiments were performed to identify the anti-tumor target of the drug. RESULTS: Eupalinilide B concentration-dependently inhibited the proliferation of laryngeal cancer cells, exhibiting potent inhibitory activity against TU686 (IC50 = 6.73 µM), TU212 (IC50 = 1.03 µM), M4e (IC50 = 3.12 µM), AMC-HN-8 (IC50 = 2.13 µM), Hep-2 (IC50 = 9.07 µM), and LCC cells (IC50 = 4.20 µM). Subsequent target verification experiments demonstrated that eupalinilide B selectively and reversibly inhibited LSD1. Furthermore, eupalinilide B, as a natural product, suppressed epithelial-mesenchymal transition in TU212 cells. An in vivo experiment further indicated that eupalinilide B could significantly reduce the growth of tumors in TU212 xenograft mouse models. CONCLUSIONS: Eupalinilide B might be a novel LSD1 inhibitor for treating laryngeal cancer.


Assuntos
Neoplasias Laríngeas , Laringe , Animais , Linhagem Celular Tumoral , Proliferação de Células , Transição Epitelial-Mesenquimal , Humanos , Neoplasias Laríngeas/tratamento farmacológico , Camundongos
17.
Front Microbiol ; 12: 727670, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34434185

RESUMO

Marine-derived fungi are a treasure house for the discovery of structurally novel secondary metabolites with potential pharmaceutical value. In this study, a pair of new nor-bisabolane derivative enantiomers (±)-1 and two new phthalides (4 and 5), as well as four known metabolites, were isolated from the culture filtrate of the marine algal-derived endophytic fungus Penicillium chrysogenum LD-201810. Their structures were established by detailed interpretation of spectroscopic data (1D/2D NMR and ESI-MS). The optical resolution of compound (±)-1 by chiral HPLC successfully afforded individual enantiomers (+)-1 and (-)-1, and their absolute configurations were determined by TDDFT-ECD calculations. Compound (±)-1 represents the first example of bisabolane analogs with a methylsulfinyl substituent group, which is rare in natural products. All of the isolated compounds 1-7 were evaluated for their cytotoxic activity against A549, BT-549, HeLa, HepG2, MCF-7, and THP-1 cell lines, as well as for antifungal activity against four plant pathogenetic fungi (Alternaria solani, Botrytis cinerea, Fusarium oxysporum, and Valsa mali). Compound 2, a bisabolane-type sesquiterpenoid, was shown to possess excellent activity for control of B. cinerea with half-maximal inhibitory concentration (IC50) of 13.6 µg/mL, whereas the remaining investigated compounds showed either weak or no cytotoxic/antifungal activity in this study.

18.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(4): 489-491, 2021 Aug 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34409808

RESUMO

Hypothyroidism is a common endocrine disease with reduced systemic metabolism, but the initial diagnosis is rare in oral and maxillofacial surgery. Due to the nonspecific symptoms, it is easy to be misdiagnosed and missed diagnosis which results in serious consequences. This paper presents a case of severe hypothyroidism which was characterized by airway obstruction, facial swelling, unexplained anaemia and bipedal edema after orthognathic surgery. With review of relevant literatures, this article discusses the risk factors, symptoms, diagnosis and therapy of hypothyroidism.


Assuntos
Hipotireoidismo , Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Edema , Ossos Faciais , Humanos , Hipotireoidismo/diagnóstico , Hipotireoidismo/etiologia
19.
J Cell Mol Med ; 25(17): 8338-8351, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34302428

RESUMO

A novel polysaccharide was extracted from Sipunculus nudus (SNP). The molecular weight (MW) of SNP was determined to be 9223 Da by high-performance gel permeation chromatography analyses, and the structure of the SNP repeat units was determined to be →3,4-ß-D-GlcpNAC (1→ and →4) -α-D-Glcp (1→ in the ratio of 15:1; →2) -α -D-Galp - (1→ as a side chain; and ß-D-Galp-(1→ and α- D-Glcp - (1→ as end groups by GC-MS analysis and NMR assays. The effect of SNP on hepatoma HepG2-bearing mice was analysed to verify its potential in the clinical treatment of liver cancer. A total of 90 male athymic nu/nu mice were divided into therapeutic and preventive groups and fed with different amounts of SNP. The antitumour effect of SNP on HepG2-bearing mice and mechanism of such were studied by analysing the tumour size, spleen index, thymus index, immune factors in the blood, tumour apoptosis factors, etc. The results suggest that SNP not only increased the index of immune organs in the body, but also enhanced the secretion of immune factors, including interleukin-2, interferon gamma and tumour necrosis factor-alpha in the serum. SNP induced the apoptosis of tumour cells via the mitochondrial apoptosis pathway, which upregulated caspase-3, caspase-8, caspase-9 and BCL2-associated X, but downregulated B-cell lymphoma-2 and vascular endothelial growth factor protein expression. In conclusion, SNP inhibited tumour growth by enhancing immune function and inducing tumour cell apoptosis in HepG2-bearing mice. Therefore, SNP may be further investigated as a promising candidate for future antitumour drugs.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Fatores Imunológicos/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Nematoides/metabolismo , Polissacarídeos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Células Hep G2 , Humanos , Masculino , Camundongos , Camundongos Nus
20.
Front Pharmacol ; 12: 637782, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33959009

RESUMO

Immune dysfunction, which is responsible for the development of human diseases including cancer, is caused by a variety of factors. Therefore, regulation of the factors influencing the immune response is a potentially effective strategy to counter diseases. Presently, several immune adjuvants are used in clinical practice to enhance the immune response and host defense ability; however, synthetic drugs can exert negative side effects. Thus, the search for natural products of plant origin as new leads for the development of potent and safe immune boosters is gaining considerable research interest. Plant-based functional foods have been shown to exert several immunomodulatory effects in humans; therefore, the application of new agents to enhance immunological and specific host defenses is a promising approach. In this comprehensive review, we have provided an up-to-date report on the use as well as the known and potential mechanisms of bioactive compounds obtained from plant-based functional foods as natural immune boosters. Plant-based bioactive compounds promote immunity through multiple mechanisms, including influencing the immune organs, cellular immunity, humoral immunity, nonspecific immunity, and immune-related signal transduction pathways. Enhancement of the immune response in a natural manner represents an excellent prospect for disease prevention and treatment and is worthy of further research and development using approaches of modern science and technology.

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