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1.
Crit Rev Eukaryot Gene Expr ; 34(6): 71-78, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38912964

RESUMO

Esophageal squamous cell carcinoma (ESCC) is a common malignancy of the gastrointestinal tract with a single therapeutic option and a lack of effective clinical therapeutic biomarkers. Extracellular matrix (ECM) remodeling plays a pro-carcinogenic role in a variety of malignancies, but its role in esophageal squamous carcinoma remains to be elucidated. In this study, we examined the expression levels of ECM remodeling markers in 71 pairs of esophageal squamous carcinoma tissues and normal tissues adjacent to the carcinoma using immunohistochemical staining, and analyzed their relationship with clinicopathological features and prognosis. The results suggested that extracellular matrix remodeling markers (integrin αV, fibronectin, MMP9) were abnormally highly expressed in esophageal squamous carcinoma tissues. There was a statistically significant difference between the positive expression of ECM remodeling and the TNM stage of esophageal squamous carcinoma, and there was no statistically significant correlation with age, gender and carcinoembryonic antigen expression, differentiation degree, T stage, and lymph node metastasis. Overall survival rate and overall survival time were significantly lower in patients with positive ECM remodeling expression, which was an independent risk factor for poor prognosisof esophageal squamous carcinoma.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Matriz Extracelular , Fibronectinas , Humanos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/genética , Masculino , Feminino , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Matriz Extracelular/metabolismo , Prognóstico , Pessoa de Meia-Idade , Fibronectinas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/genética , Idoso , Metaloproteinase 9 da Matriz/metabolismo , Integrina alfaV/metabolismo , Integrina alfaV/genética , Estadiamento de Neoplasias , Regulação Neoplásica da Expressão Gênica , Metástase Linfática , Adulto
2.
Small ; 20(8): e2304110, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37806756

RESUMO

Atherosclerosis (AS) is the primary reason behind cardiovascular diseases, leading to approximately one-third of global deaths. Developing a novel multi-model probe to detect AS is urgently required. Macrophages are the primary cells from which AS genesis occurs. Utilizing natural macrophage membranes coated on the surface of nanoparticles is an efficient delivery method to target plaque sites. Herein, Fe3 O4 -Cy7 nanoparticles (Fe3 O4 -Cy7 NPs), functionalized using an M2 macrophage membrane and a liposome extruder for Near-infrared fluorescence and Magnetic resonance imaging, are synthesized. These macrophage membrane-coated nanoparticles (Fe3 O4 @M2 NPs) enhance the recognition and uptake using active macrophages. Moreover, they inhibit uptake using inactive macrophages and human coronary artery endothelial cells. The macrophage membrane-coated nanoparticles (Fe3 O4 @M0 NPs, Fe3 O4 @M1 NPs, Fe3 O4 @M2 NPs) can target specific sites depending on the macrophage membrane type and are related to C-C chemofactor receptor type 2 protein content. Moreover, Fe3 O4 @M2 NPs demonstrate excellent biosafety in vivo after injection, showing a significantly higher Fe concentration in the blood than Fe3 O4 -Cy7 NPs. Therefore, Fe3 O4 @M2 NPs effectively retain the physicochemical properties of nanoparticles and depict reduced immunological response in blood circulation. These NPs mainly reveal enhanced targeting imaging capability for atherosclerotic plaque lesions.


Assuntos
Aterosclerose , Nanopartículas , Humanos , Células Endoteliais , Nanopartículas/química , Imageamento por Ressonância Magnética/métodos , Aterosclerose/diagnóstico por imagem
3.
Stat Med ; 43(11): 2062-2082, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38757695

RESUMO

This paper discusses regression analysis of interval-censored failure time data arising from semiparametric transformation models in the presence of missing covariates. Although some methods have been developed for the problem, they either apply only to limited situations or may have some computational issues. Corresponding to these, we propose a new and unified two-step inference procedure that can be easily implemented using the existing or standard software. The proposed method makes use of a set of working models to extract partial information from incomplete observations and yields a consistent estimator of regression parameters assuming missing at random. An extensive simulation study is conducted and indicates that it performs well in practical situations. Finally, we apply the proposed approach to an Alzheimer's Disease study that motivated this study.


Assuntos
Doença de Alzheimer , Simulação por Computador , Modelos Estatísticos , Humanos , Análise de Regressão , Interpretação Estatística de Dados
4.
Org Biomol Chem ; 22(13): 2562-2565, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38451158

RESUMO

A radical initiator-free defunctionalization reaction of alkyl isocyanides with a hydrosilane has been established through C-N bond cleavage under catalyst-free visible light irradiation. Various alkyl isocyanides participated in the defunctionalization with tris(trimethylsilyl)silane under blue light irradiation at room temperature, delivering the reduced products in good yields with high chemoselectivity.

5.
Bioorg Chem ; 146: 107320, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38569323

RESUMO

Spleen tyrosine kinase (Syk) plays a crucial role as a target for allergy treatment due to its involvement in immunoreceptor signaling. The purpose of this study was to identify natural inhibitors of Syk and assess their effects on the IgE-mediated allergic response in mast cells and ICR mice. A list of eight compounds was selected based on pharmacophore and molecular docking, showing potential inhibitory effects through virtual screening. Among these compounds, sophoraflavanone G (SFG) was found to inhibit Syk activity in an enzymatic assay, with an IC50 value of 2.2 µM. To investigate the conformational dynamics of the SYK-SFG system, we performed molecular dynamics simulations. The stability of the binding between SFG and Syk was evaluated using root mean square deviation (RMSD) and root mean square fluctuation (RMSF). In RBL-2H3 cells, SFG demonstrated a dose-dependent suppression of IgE/BSA-induced mast cell degranulation, with no significant cytotoxicity observed at concentrations below 10.0 µM within 24 h. Furthermore, SFG reduced the production of TNF-α and IL-4 in RBL-2H3 cells. Mechanistic investigations revealed that SFG inhibited downstream signaling proteins, including phospholipase Cγ1 (PLCγ1), as well as mitogen-activated protein kinases (AKT, Erk1/2, p38, and JNK), in mast cells in a dose-dependent manner. Passive cutaneous anaphylaxis (PCA) experiments demonstrated that SFG could reduce ear swelling, mast cell degranulation, and the expression of COX-2 and IL-4. Overall, our findings identify naturally occurring SFG as a direct inhibitor of Syk that effectively suppresses mast cell degranulation both in vitro and in vivo.


Assuntos
Interleucina-4 , Mastócitos , Camundongos , Animais , Interleucina-4/metabolismo , Interleucina-4/farmacologia , Mastócitos/metabolismo , Anafilaxia Cutânea Passiva , Simulação de Acoplamento Molecular , Imunoglobulina E/metabolismo , Imunoglobulina E/farmacologia , Camundongos Endogâmicos ICR , Camundongos Endogâmicos BALB C
6.
Environ Res ; 255: 119173, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38763280

RESUMO

The rapid development of modern society has led to an increasing severity in the generation of new pollutants and the significant emission of old pollutants, exerting considerable pressure on the ecological environment and posing a serious threat to both biological survival and human health. The skeletal system, as a vital supportive structure and functional unit in organisms, is pivotal in maintaining body shape, safeguarding internal organs, storing minerals, and facilitating blood cell production. Although previous studies have uncovered the toxic effects of pollutants on vertebrate skeletal systems, there is a lack of comprehensive literature reviews in this field. Hence, this paper systematically summarizes the toxic effects and mechanisms of environmental pollutants on the skeletons of vertebrates based on the evolutionary context from fish to mammals. Our findings reveal that current research mainly focuses on fish and mammals, and the identified impact mechanisms mainly involve the regulation of bone signaling pathways, oxidative stress response, endocrine system disorders, and immune system dysfunction. This study aims to provide a comprehensive and systematic understanding of research on skeletal toxicity, while also promoting further research and development in related fields.


Assuntos
Poluentes Ambientais , Peixes , Mamíferos , Animais , Poluentes Ambientais/toxicidade , Osso e Ossos/efeitos dos fármacos , Evolução Biológica , Vertebrados
7.
Planta Med ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38838717

RESUMO

Thrombin is a crucial enzyme in the coagulation cascade, and inhibitors of thrombin have been extensively studied as potential antithrombotic agents. The objective of this study was to identify natural inhibitors of thrombin from Panax notoginseng and evaluate their biological activity in vitro and binding characteristics. A combined approach involving molecular docking, thrombin inhibition assays, surface plasmon resonance, and molecular dynamics simulation was utilized to identify natural thrombin inhibitors. The results demonstrated that panaxatriol directly inhibits thrombin, with an IC50 of 10.3 µM. Binding studies using surface plasmon resonance revealed that panaxatriol interacts with thrombin, with a KD value of 7.8 µM. Molecular dynamics analysis indicated that the thrombin-panaxatriol system reached equilibrium rapidly with minimal fluctuations, and the calculated binding free energy was - 23.8 kcal/mol. The interaction between panaxatriol and thrombin involves the amino acid residues Glu146, Glu192, Gly216, Gly219, Tyr60A, and Trp60D. This interaction provides a mechanistic basis for further optimizing panaxatriol as a thrombin inhibitor. Our study has shown that panaxatriol serves as a direct thrombin inhibitor, laying the groundwork for further research and development of novel thrombin inhibitors.

8.
Int J Mol Sci ; 25(1)2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38203765

RESUMO

Classical swine fever virus (CSFV) is a highly contagious pathogen causing significant economic losses in the swine industry. Conventional inactivated or attenuated live vaccines for classical swine fever (CSF) are effective but face biosafety concerns and cannot distinguish vaccinated animals from those infected with the field virus, complicating CSF eradication efforts. It is noteworthy that nanoparticle (NP)-based vaccines resemble natural viruses in size and antigen structure, and offer an alternative tool to circumvent these limitations. In this study, we developed an innovative vaccine delivery scaffold utilizing self-assembled mi3 NPs, which form stable structures carrying the CSFV E2 glycoprotein. The expressed yeast E2-fused protein (E2-mi3 NPs) exhibited robust thermostability (25 to 70 °C) and long-term storage stability at room temperature (25 °C). Interestingly, E2-mi3 NPs made with this technology elicited enhanced antigen uptake by RAW264.7 cells. In a rabbit model, the E2-mi3 NP vaccine against CSFV markedly increased CSFV-specific neutralizing antibody titers. Importantly, it conferred complete protection in rabbits challenged with the C-strain of CSFV. Furthermore, we also found that the E2-mi3 NP vaccines triggered stronger cellular (T-lymphocyte proliferation, CD8+ T-lymphocytes, IFN-γ, IL-2, and IL-12p70) and humoral (CSFV-specific neutralizing antibodies, CD4+ T-lymphocytes, and IL-4) immune responses in pigs than the E2 vaccines. To sum up, these structure-based, self-assembled mi3 NPs provide valuable insights for novel antiviral strategies against the constantly infectious agents.


Assuntos
Vírus da Febre Suína Clássica , Peste Suína Clássica , Lagomorpha , Nanopartículas , Animais , Coelhos , Suínos , Nanovacinas , Peste Suína Clássica/prevenção & controle , Vacinas Atenuadas , Proteínas Fúngicas
9.
Molecules ; 29(10)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38792165

RESUMO

The objective of this study was to identify multiple alkaloids in Coptis chinensis that demonstrate inhibitory activity against DPP-4 and systematically evaluate their activity and binding characteristics. A combined strategy that included molecular docking, a DPP-4 inhibition assay, surface plasmon resonance (SPR), and a molecular dynamics simulation technique was employed. The results showed that nine alkaloids in Coptis chinensis directly inhibited DPP-4, with IC50 values of 3.44-53.73 µM. SPR-based binding studies revealed that these alkaloids display rapid binding and dissociation characteristics when interacting with DPP-4, with KD values ranging from 8.11 to 29.97 µM. A molecular dynamics analysis revealed that equilibrium was rapidly reached by nine DPP-4-ligand systems with minimal fluctuations, while binding free energy calculations showed that the ∆Gbind values for the nine test compounds ranged from -31.84 to -16.06 kcal/mol. The most important forces for the binding of these alkaloids with DPP-4 are electrostatic interactions and van der Waals forces. Various important amino acid residues, such as Arg125, His126, Phe357, Arg358, and Tyr547, were involved in the inhibition of DPP-4 by the compounds, revealing a mechanistic basis for the further optimization of these alkaloids as DPP-4 inhibitors. This study confirmed nine alkaloids as direct inhibitors of DPP-4 and characterized their binding features, thereby providing a basis for further research and development on novel DPP-4 inhibitors.


Assuntos
Alcaloides , Coptis , Dipeptidil Peptidase 4 , Inibidores da Dipeptidil Peptidase IV , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Inibidores da Dipeptidil Peptidase IV/química , Inibidores da Dipeptidil Peptidase IV/farmacologia , Coptis/química , Dipeptidil Peptidase 4/química , Dipeptidil Peptidase 4/metabolismo , Alcaloides/química , Alcaloides/farmacologia , Ligação Proteica , Humanos , Sítios de Ligação , Ressonância de Plasmônio de Superfície , Descoberta de Drogas/métodos
10.
Pathol Int ; 73(4): 147-158, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36734588

RESUMO

Esophageal cancer (EC) is one of the most frequent cancers with a higher mortality worldwide. Although prolyl 4-hydroxylase alpha polypeptide I (P4HA1) is involved in various human malignancies, the function of P4HA1 in EC remains unclear. The mRNA and protein expressions were assessed by quantitative real-time polymerase chain reaction, western blot and immunohistochemistry. CCK8 assay was used to detect EC cell viability. Cell proliferation was analyzed by colony formation and ethynyl-2'-deoxyuridine assays. In addition, flow cytometry and TdT-mediated dUTP nick-end labeling staining were performed to detect cell apoptosis. Masson's trichrome staining was used to assess the collagen fiber level in tumor tissues. The interaction between STAT1 and P4HA4 was analyzed using ChIP, dual-luciferase reporter gene and Y1H assays. P4HA1 was overexpressed in EC, and its knockdown suppressed EC cell proliferation and collagen synthesis and increased cell apoptosis. Meanwhile, P4HA1 knockdown could repress EC tumor growth in vivo. Our further research displayed that STAT1 promoted P4HA1 expression by interacting with P4HA1 promoter. As expected, P4HA1 overexpression abolished STAT1 knockdown's repression on EC cell malignant behaviors. Our research proved that P4HA1 was transcriptionally activated by STAT1, thereby promoting EC progression.


Assuntos
Neoplasias Esofágicas , MicroRNAs , Pró-Colágeno-Prolina Dioxigenase , Fator de Transcrição STAT1 , Humanos , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Colágeno/metabolismo , Neoplasias Esofágicas/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Pró-Colágeno-Prolina Dioxigenase/genética , Pró-Colágeno-Prolina Dioxigenase/metabolismo , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo
11.
Ecotoxicol Environ Saf ; 259: 115064, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37229873

RESUMO

Pomacea canaliculata is a malignant invasive aquatic snail found worldwide, and niclosamide (NS) is one of the primary agents used for its control. NS applied to water will exist in non-lethal concentrations for some time due to degradation or water exchange, thus resulting in sublethal effects on environmental organisms. To identify sublethal effects of NS on Pomacea canaliculata, we studied the aspects of histopathology, oxygen-nitrogen ratio (RO∶N), enzyme activity determination, and gene expression. After LC30 NS treatment (0.310 g/L), many muscle fibers of the feet degenerated and some acinar vesicles of the hepatopancreas collapsed and dissolved. The oxygen-nitrogen ratio (RO∶N) decreased significantly from 15.0494 to 11.5183, indicating that NS had changed the metabolic mode of Pomacea canaliculata and shifted it primarily to protein catabolism. Transcriptome analysis identified the sublethal effects of LC30 NS on the snails at the transcriptional level. 386, 322, and 583 differentially expressed genes (DEGs) were identified in the hepatopancreas, gills, and feet, respectively. GO (Gene Ontology) functional analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway annotations showed that DEGs in the hepatopancreas were mainly enriched for sugar metabolism, protein biosynthesis, immune response, and amino acid metabolism functional categories; DEGs in the gills were mainly enriched for ion transport and amino acid metabolism; DEGs in the feet were mainly enriched for transmembrane transport and inositol biosynthesis. In the future, we will perform functional validation of key genes to further explain the molecular mechanism of sublethal effects.


Assuntos
Alimentos , Niclosamida , Animais , Niclosamida/toxicidade , Metabolismo dos Carboidratos , Água , Aminoácidos
12.
Pestic Biochem Physiol ; 192: 105424, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37105626

RESUMO

Virtual screening is an efficient way to obtain new drugs, which has become an important method in the field of pesticide research. Protein neural wiskott-Aldrich syndrome isoform X1 (PcnWAS) is a target protein that exists in the haemocytes of Pomacea canaliculata, and in this study, isothermal titration calorimetry (ITC) was used to evaluate the binding ability of protein PcnWAS and pedunsaponin A in vitro. Furthermore, it was set as a receptor, and the design of molluscicidal compounds based on protein PcnWAS was carried out. Results showed that, pedunsaponin A had high binding capacity with protein PcnWAS, and the binding constant (Ka) was 2.98 ± 1.74 × 10-4. A new potential molluscicidal compound thionicotinamide-adenine-dinucleotide (thionicotinamide-DPN) was obtained by virtual screening. In-vivo bioassay indicated that, the LC50 value was 57.7102 mg/L (72 h), and the oxygen consumption rate, ammonia excretion rate, oxygen nitrogen ratio and hemocyanin content of P. canaliculata declined after 60 mg/L thionicotinamide-DPN treated. Furthermore, the treatment of thionicotinamide-DPN also decreased gene expression level of protein PcnWAS. The results of ITC test showed that thionicotinamide-DPN can bind with protein PcnWAS efficiently, which means that it has the same target with pedunsaponin A when interacted with P. canaliculata. All the above results lay a foundation for the development of new molluscicides.


Assuntos
Moluscocidas , Saponinas , Triterpenos , Animais , Caramujos , Moluscocidas/farmacologia , Proteínas
13.
Ecotoxicol Environ Saf ; 246: 114198, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36272173

RESUMO

Pomacea canaliculata, as an invasive snail in China, can adversely affect agricultural crop yields, ecological environment, and human health. In this paper, we studied the molluscicidal activity and mechanisms of arecoline against P. canaliculata. The molluscicidal activity tests showed that arecoline exhibits strong toxicity against P. canaliculata, and the LC50 value (72 h) was 1.05 mg/L (15 ± 2 mm shell diameter). Additionally, Molluscicidal toxicity were negatively correlated with the size of snails. Snails (25 ± 2 mm shell diameter) were choosed for mechanisms research and the result of microstructure and biochemistry showed that arecoline (4 mg/L, 20 â„ƒ) had strong toxic effect on the gill, and the main signs were the loss of cilia in the gill filaments. Moreover, arecoline significantly decreased the oxygen consumption rate, ammonia excretion rate and inhibited acetylcholinesterase (AChE). Then, the changes in protein expression were studied by iTRAQ, and 526 downregulated proteins were found. Among these, cilia and flagella-associated 157-like (PcCFP) and rootletin-like (PcRoo) were selected as candidate target proteins through bioinformatics analysis, and then RNA interference (RNAi) was adopted to verify the function of PcCFP and PcRoo. The results showed that after arecoline treated, the mortality and the cilia shedding rate of PcRoo RNAi treated group was significantly lower than control group. The above results indicate that arecoline can bind well with protein PcRoo, and then leads to the drop of gill cilia, affect respiratory metabolism, accelerate its entry into hemolymph, inhibit AChE and finally leads to the death of P. canaliculata.


Assuntos
Gastrópodes , Moluscocidas , Animais , Humanos , Arecolina , Acetilcolinesterase , Moluscocidas/toxicidade , Dose Letal Mediana
14.
Zhongguo Zhong Yao Za Zhi ; 47(5): 1316-1326, 2022 Mar.
Artigo em Zh | MEDLINE | ID: mdl-35343160

RESUMO

This study was aimed to explore the effect of Zingiberis Rhizoma extract on rats with antibiotic-associated diarrhea(AAD), and reveal the modulation of gut microbiota during alleviation of AAD. AAD rat model was successfully established by exposing rats to appropriate antibiotic mixed solution. Peficon(70 mg·kg~(-1)·d~(-1)) was used as positive control, then rats were treated with 200 mg·kg~(-1)·d~(-1) and 400 mg·kg~(-1)·d~(-1) of Zingiberis Rhizoma extract for low and high dosage groups of Zingiberis Rhizoma extract, respectively. The weight changes of the rats were observed, and the degree of diarrhea were evaluated by fecal score, 120 min fecal weight and fecal water content. Colon tissues for histopathological examination were stained with hematoxylin and eosin(HE), and 16 S rRNA sequencing analysis of gut microbiota was performed. The results showed that compared with the model group, the degree of diarrhea, indicated by fecal water content, fecal score, and 120 min fecal weight of positive control group, Zingiberis Rhizoma low-dose group and Zingiberis Rhizoma high-dose group were significantly ameliorated. And the treatment of Zingiberis Rhizoma could significantly improve the pathological condition of colon tissue in AAD rats, especially the high dose of Zingiberis Rhizoma. In addition, 16 S rRNA sequencing analysis of gut microbiota showed that the diversity and abundance of gut microbiota were significantly improved and the reco-very of gut microbiota was accelerated after given high-dose of Zingiberis Rhizoma, while no significant changes of alterations were observed after given Pefikon. Of note, compared with the pefikon group, the abundance and diversity of gut microbiota in Zingi-beris Rhizoma high-dose group were significantly elevated. At the phylum level, the abundance of Firmicutes in AAD rats increased and the abundance of Proteobacteria was decreased after the Zingiberis Rhizoma intervention. At the genus level, the abundance of Bacillus spp., Lachnoclostridium and Escherichia coli-Shigella were decreased, and the abundance of Lactobacillus spp., Trichophyton spp., and Trichophyton spp., etc., were increased. While compared with the AAD model group, there was no significant difference of gut microbiota after given Peficon. The results showed that Zingiberis Rhizoma exerted beneficial health effects against AAD, and positively affected the microbial environment in the gut of rats with AAD.


Assuntos
Microbioma Gastrointestinal , Animais , Antibacterianos/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Zingiber officinale , Extratos Vegetais , Ratos , Rizoma
15.
BMC Infect Dis ; 21(1): 805, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384388

RESUMO

BACKGROUND: Since the COVID-19 pandemic, several therapeutic agents have been used in COVID-19 management. However, the results were controversial. Here, we aimed to evaluate the efficacy and safety of hydroxychloroquine (HCQ)/chloroquine (CQ) in COVID-19. METHODS: We retrospectively reviewed the medical charts of patients with COVID-19 admitted to an inpatient ward in Wuhan from 2020/Feb/08 to 2020/Mar/05. Patients with HCQ/CQ and age, gender, disease severity matched ones without HCQ/CQ were selected at a 1:2 ratio. The clinical, laboratory and imaging findings were compared between these two groups. The multivariate linear regression analysis was performed to identify the factors that might influence patients' virus shedding periods (VSPs). RESULTS: A total of 14 patients with HCQ/CQ and 21 matched ones were analyzed. The HCQ/CQ treatment lasted for an average of 10.36 ± 3.12 days. The mean VSPs were longer in the HCQ/CQ treatment group (26.57 ± 10.35 days vs. 19.10 ± 7.80 days, P = 0.020). There were 3 patients deceased during inpatient period, two patients were with HCQ/CQ treatment (P = 0.551). In the multivariate linear regression analysis, disease durations at admission (t = 3.643, P = 0.001) and HCQ/CQ treatment (t = 2.637, P = 0.013) were independent parameters for patients' VSPs. One patient with CQ had recurrent first-degree atrioventricular block (AVB) and obvious QTc elongation, another one complained about dizziness and blurred vision which disappeared after CQ discontinuation. One patient with HCQ had transient AVB. CONCLUSIONS: In summary, we identify that the HCQ/CQ administration is not related to less mortality cases at later phase of COVID-19. More studies are needed to explore whether HCQ/CQ treatment would lead to SARS-Cov-2 RNA clearance delay or not.


Assuntos
Tratamento Farmacológico da COVID-19 , Hidroxicloroquina , Cloroquina , Humanos , Hidroxicloroquina/efeitos adversos , Pandemias , RNA Viral , Estudos Retrospectivos , SARS-CoV-2
16.
Pestic Biochem Physiol ; 179: 104963, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34802513

RESUMO

Glabridin is a natural plant-derived compound that has been widely used in medicine and cosmetic applications. However, the fungicidal mechanism of glabridin against phytopathogens remains unclear. In this study, we determined the biological activity and physiological effects of glabridin against F. graminearum. Then the differentially expressed proteins of F. graminearum were screened. The EC50 values of glabridin in inhibiting the mycelial growth and conidial germination of F. graminearum were 110.70 mg/L and 40.47 mg/L respectively. Glabridin-induced cell membrane damage was indicated by morphological observations, DiBAC4(3) and PI staining, and measurements of relative conductivity, ergosterol content and respiratory rates. These assays revealed that the integrity of the membrane was destroyed, the content of ergosterol decreased, and the respiratory rate was inhibited. A proteomics analysis showed that 186 proteins were up-regulated and 195 proteins were down-regulated. Mechanically sensitive ion channel proteins related to transmembrane transport and ergosterol biosynthesis ERG4/ERG24, related to ergosterol synthesis were blocked. It is speculated that glabridin acts on ergosterol synthesis-related proteins to destroy the integrity of the cell membrane, resulting in abnormal transmembrane transport and an increased membrane potential. Finally, the morphology of mycelia was seriously deformed, growth and development were inhibited. As a result death was even induced.


Assuntos
Fungicidas Industriais , Fusarium , Isoflavonas , Fenóis/farmacologia , Doenças das Plantas
17.
J Ultrasound Med ; 39(3): 453-461, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31448445

RESUMO

OBJECTIVES: To investigate fetal hemodynamic alterations using transabdominal ultrasound in fetuses with isolated mild-to-moderate ventriculomegaly (VM). METHODS: Fetuses diagnosed with isolated mild-to-moderate VM by transabdominal ultrasound were evaluated for hemodynamic changes, including changes in fetal cardiac function, the umbilical artery, the ductus venosus, and the middle cerebral artery. The fetuses with isolated mild-to-moderate VM were divided into 2 groups, namely, before 32 weeks' gestation (20 weeks-31 weeks 6 days) and after 32 weeks' gestation (32-38 weeks), and matched to corresponding healthy control fetuses. RESULTS: The 53 fetuses with VM before 32 weeks had a longer mean isovolumetric relaxation time (IRT; mean ± SD, 42.9 ± 6.8 versus 40.4 ± 5.0 milliseconds; P < .05) and an apparently higher modified myocardial performance index 0.46 ± 0.06 versus 0.43 ± 0.05; P < .01) than the healthy control fetuses. The 43 fetuses with VM after 32 weeks had a significantly longer mean IRT (45.5 ± 6.7 versus 40.9 ± 7.2 milliseconds; P < .01) and a lower UA pulsatility index (0.81 ± 0.13 versus 0.89 ± 0.11; P < .01). The optimal cutoff levels for the IRT in the prediction of adverse perinatal outcomes were 40 and 43 milliseconds before and after 32 weeks, respectively (sensitivity, 100% versus 100%; specificity, 40.4% versus 50.0%; area under the curve, 0.601 versus 0.748; 95% confidence interval, 0.457-0.733 versus 0.590-0.869; P = .291 versus .005). CONCLUSIONS: Some fetuses with isolated mild-to-moderate VM may have impaired cardiac function, characterized by a higher modified myocardial performance index or longer IRT. This finding might be useful for improving fetal surveillance.


Assuntos
Coração Fetal/diagnóstico por imagem , Coração Fetal/fisiopatologia , Hemodinâmica/fisiologia , Hidrocefalia/embriologia , Hidrocefalia/fisiopatologia , Ultrassonografia Pré-Natal/métodos , Adulto , Estudos Transversais , Feminino , Coração Fetal/embriologia , Humanos , Hidrocefalia/diagnóstico por imagem , Gravidez , Estudos Prospectivos , Índice de Gravidade de Doença , Ultrassonografia Doppler/métodos , Adulto Jovem
18.
J Fluoresc ; 29(3): 577-586, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30937611

RESUMO

A novel naphthalene based fluorescence probe NBDH was designed and synthesized. Probe NBDH exhibited highly selective and sensitive responses towards Al3+ in HEPES-NaOH buffer solution (pH = 7.4). In addition, the detection of NBDH to Al3+ could be achieved through dual channels embodied in significant fluorescent turn-on signal and ratiometric absorbance response. The stoichiometry ratio of NBDH-Al3+ was 1:1 by fluorescence job' plot and binging mechanism was further varified by the FT-IR, NMR titration and HRMS. Furthermore, NBDH was achieved in real sample detection, and a series of color test paper were developed for visual detecting Al3+ ions.

19.
Future Oncol ; 15(36): 4181-4195, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31789057

RESUMO

Aim: We mainly explored the effect of SOX2, ß-catenin and survivin on prognosis in esophageal squamous cell carcinoma. Materials & methods: Immunohistochemistry was used to examine the expression of SOX2, ß-catenin and survivin. χ2 test was used to analyze the relationship between proteins and clinicopathological parameters. Survival analysis was used to investigate the effect of three proteins on prognosis. Results: SOX2 was related to lymph node metastasis (p = 0.004) and vascular invasion (p = 0.041). ß-catenin was associated with depth of invasion (p = 0.014), lymph node metastasis (p = 0.032) and postoperative chemoradiotherapy (p < 0.001). Survivin was related to gender (p = 0.022) and nerve invasion (p = 0.014). There was a positive correlation between SOX2 and ß-catenin. Patients with SOX2 and ß-catenin overexpression had poor prognosis. Survivin-positive patients who received postoperative chemoradiotherapy had a short time. Conclusion: SOX2, ß-catenin and survivin can be used as prognostic markers of esophageal squamous cell carcinoma.


Assuntos
Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/mortalidade , Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição SOXB1/genética , Survivina/genética , beta Catenina/genética , Adulto , Idoso , Biomarcadores Tumorais , Quimiorradioterapia , Terapia Combinada , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Carcinoma de Células Escamosas do Esôfago/terapia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico
20.
J Fluoresc ; 28(1): 347-357, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29143241

RESUMO

A novel naphthalimide-based colorimetric and fluorescent turn-on chemosensor for Al3+ was synthesized and characterized with spectroscopic techniques. In MeOH solution, BPAM showed high selectivity and sensitivity to Al3+ by a 60-fold fluorescence enhancement and blue-shift absorption with visible color changes attributed to the contribution of chelation enhanced fluorescence (CHEF) and inhibition of intramolecular charge transfer (ICT). A 1:1 BPAM-Al3+ complex confirmed by job's plot and HRMS with a binding constant of 6.37 × 104 M- 1, and the detection limit for Al3+ was as low as 1.59 × 10- 7 M. BPAM was successfully applied in real sample detection and assessing the existence of Al3+ by a colorimetric method on filter paper. Furthermore, the fluorescent signals of BPAM were designed to construct an INHIBIT molecular logic gate.

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