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1.
Acta Pharmacol Sin ; 45(9): 1861-1878, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38719955

RESUMO

Pulmonary hypertension (PH) is a progressive fatal disease with no cure. Canagliflozin (CANA), a novel medication for diabetes, has been found to have remarkable cardiovascular benefits. However, few studies have addressed the effect and pharmacological mechanism of CANA in the treatment of PH. Therefore, our study aimed to investigate the effect and pharmacological mechanism of CANA in treating PH. First, CANA suppressed increased pulmonary artery pressure, right ventricular hypertrophy, and vascular remodeling in both mouse and rat PH models. Network pharmacology, transcriptomics, and biological results suggested that CANA could ameliorate PH by suppressing excessive oxidative stress and pulmonary artery smooth muscle cell proliferation partially through the activation of PPARγ. Further studies demonstrated that CANA inhibited phosphorylation of PPARγ at Ser225 (a novel serine phosphorylation site in PPARγ), thereby promoting the nuclear translocation of PPARγ and increasing its ability to resist oxidative stress and proliferation. Taken together, our study not only highlighted the potential pharmacological effect of CANA on PH but also revealed that CANA-induced inhibition of PPARγ Ser225 phosphorylation increases its capacity to counteract oxidative stress and inhibits proliferation. These findings may stimulate further research and encourage future clinical trials exploring the therapeutic potential of CANA in PH treatment.


Assuntos
Canagliflozina , Proliferação de Células , Hipertensão Pulmonar , Estresse Oxidativo , PPAR gama , Animais , Masculino , Camundongos , Ratos , Canagliflozina/farmacologia , Canagliflozina/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/metabolismo , Camundongos Endogâmicos C57BL , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , PPAR gama/metabolismo , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Ratos Sprague-Dawley , Remodelação Vascular/efeitos dos fármacos , Serina/química , Serina/metabolismo
2.
Am J Otolaryngol ; 45(4): 104296, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38653084

RESUMO

BACKGROUND: Narrow-band imaging (NBI) endoscopy is used in various tumor detection and is important in detecting early tumors. OBJECTIVE: To explore the application value of NBI endoscopy in diagnosing pharyngeal tumors. MATERIAL AND METHODS: Ninety-one patients with pharyngeal masses who attended the Department of Otorhinolaryngology, Head and Neck Surgery in Gansu Provincial Hospital from January 2023 to February 2024 were selected, and NBI and white light (WL) endoscopy were applied to examine the pharynx and the relationship between the two was observed. SPSS 25.0 software was used for statistical analysis. RESULTS: The sensitivity of NBI endoscopy for diagnosing laryngeal malignant lesions was 92.0 %, the specificity was 93.0 %, the positive predictive value was 88.5 %, and the negative predictive value was 95.2 %, with a high degree of concordance between the results of NBI endoscopy and the pathology; WL endoscopy had a sensitivity of 64.0 %, a specificity of 76. 7 %, a positive predictive value of 61.5 %, and a negative predictive value of 78.6 %, with WL endoscopic findings had moderate concordance with pathology. The diagnostic accuracy of NBI endoscopy was higher than that of WL endoscopy for both benign and malignant lesions and precancerous lesions. CONCLUSION: NBI endoscopy can detect laryngeal cancer lesions more accurately.


Assuntos
Endoscopia , Imagem de Banda Estreita , Neoplasias Faríngeas , Sensibilidade e Especificidade , Humanos , Imagem de Banda Estreita/métodos , Neoplasias Faríngeas/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Endoscopia/métodos , Valor Preditivo dos Testes , Idoso de 80 Anos ou mais , Neoplasias Laríngeas/diagnóstico por imagem , Neoplasias Laríngeas/patologia
3.
J Environ Manage ; 368: 122115, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39121628

RESUMO

Biological treatment represents a fundamental component of wastewater treatment plants (WWTPs). The transmission of antibiotic resistance bacteria (ARB) and resistance genes (ARGs) occurred through the continuous migration and transformation, attributed to the residual presence of antibiotics in WWTPs effluent, posing a significant threat to the entire ecosystem. It is necessary to propose novel biological strategies to address the challenge of refractory contaminants, such as antibiotics, ARGs and ARB. This review summarizes the occurrence of antibiotics in wastewater, categorized by high and low concentrations. Additionally, current biological treatments used in WWTPs, such as aerobic activated sludge, anaerobic digestion, sequencing batch reactor (SBR), constructed wetland, membrane-related bioreactors and biological aerated filter (BAF) are introduced. In particular, because microorganisms are the key to those biological treatments, the effect of high and low concentration of antibiotics on microorganisms are thoroughly discussed. Finally, solutions involving functional bacteria, partial nitrification (PN)-Anammox and lysozyme embedding are suggested from the perspective of the entire biological treatment process. Overall, this review provides valuable insights for the simultaneous removal of antibiotics and ARGs in antibiotics wastewater.


Assuntos
Antibacterianos , Águas Residuárias , Antibacterianos/farmacologia , Eliminação de Resíduos Líquidos/métodos , Reatores Biológicos , Resistência Microbiana a Medicamentos/genética , Esgotos/microbiologia
4.
Angew Chem Int Ed Engl ; 63(37): e202403541, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-38885002

RESUMO

The exploration of cell-based drug delivery systems for cancer therapy has gained growing attention. Approaches to engineering therapeutic cells with multidrug loading in an effective, safe, and precise manner while preserving their inherent biological properties remain of great interest. Here, we report a strategy to simultaneously load multiple drugs in platelets in a one-step fusion process. We demonstrate doxorubicin (DOX)-encapsulated liposomes conjugated with interleukin-15 (IL-15) could fuse with platelets to achieve both cytoplasmic drug loading and surface cytokine modification with a loading efficiency of over 70 % within minutes. Due to their inherent targeting ability to metastatic cancers and postoperative bleeding sites, the engineered platelets demonstrated a synergistic therapeutic effect to suppress lung metastasis and postoperative recurrence in mouse B16F10 melanoma tumor models.


Assuntos
Plaquetas , Doxorrubicina , Animais , Camundongos , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Melanoma Experimental/patologia , Melanoma Experimental/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/patologia , Lipossomos/química , Sistemas de Liberação de Medicamentos
5.
J Pharmacol Exp Ther ; 387(3): 288-298, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37875309

RESUMO

Epstein-Barr virus (EBV) is a type of human γ-herpesvirus, and its reactivation plays an important role in the development of EBV-driven Burkitt lymphoma (BL). Despite intensive chemotherapy, the prognosis of relapsed/refractory BL patients remains unfavorable, and a definitive method to completely eliminate latent EBV infection is lacking. Previous studies have demonstrated that histone deacetylase (HDAC) inhibitors can induce the transition of EBV from latency to the lytic phase. The lytic activation of EBV can be inhibited by tenofovir, a potent inhibitor of DNA replication. Herein, we explored the antitumor effect and EBV clearance potential of a novel HDAC inhibitor called chidamide, combined with tenofovir, in the treatment of EBV-positive BL. In the study, chidamide exhibited inhibitory activity against HDAC. Moreover, chidamide inhibited BL cell proliferation, arrested cell cycle progression, and induced BL cell apoptosis primarily by regulating the MAPK pathways. Additionally, chidamide promoted the transcription of lytic genes, including BZLF1, BMRF1, and BMLF1 Compared with chidamide alone, the addition of tenofovir further induced growth arrest and apoptosis in EBV-positive BL cells and inhibited the transcriptions of EBV lytic genes induced by chidamide alone. Furthermore, our in vivo data demonstrated that the combination of chidamide and tenofovir had superior tumor-suppressive effects in a mouse model of BL cell tumors. The aforementioned findings confirm the synergistic effect of chidamide combined with tenofovir in inducing growth inhibition and apoptosis in EBV-positive BL cells and provide an effective strategy for eliminating EBV and EBV-associated malignancies. SIGNIFICANCE STATEMENT: High levels of Epstein-Barr virus (EBV)-DNA have consistently been associated with unfavorable progression-free survival and overall survival in EBV-associated lymphomas. Therefore, identifying novel strategies to effectively eradicate tumor cells and eliminate EBV is crucial for lymphoma patients. This study confirmed, for the first time, the synergistic effect of chidamide combined with tenofovir in the treatment of Burkitt lymphoma and the eradication of EBV virus.


Assuntos
Linfoma de Burkitt , Infecções por Vírus Epstein-Barr , Linfoma , Animais , Camundongos , Humanos , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/patologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/metabolismo , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Tenofovir/farmacologia , Tenofovir/uso terapêutico , Tenofovir/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico
6.
Sensors (Basel) ; 23(12)2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37420911

RESUMO

An innovative optical frequency-domain reflectometry (OFDR)-based distributed temperature sensing method is proposed that utilizes a Rayleigh backscattering enhanced fiber (RBEF) as the sensing medium. The RBEF features randomly high backscattering points; the analysis of the fiber position shift of these points before and after the temperature change along the fiber is achieved using the sliding cross-correlation method. The fiber position and temperature variation can be accurately demodulated by calibrating the mathematical relationship between the high backscattering point position along the RBEF and the temperature variation. Experimental results reveal a linear relationship between temperature variation and the total position displacement of high backscattering points. The temperature sensing sensitivity coefficient is 7.814 µm/(m·°C), with an average relative error temperature measurement of -1.12% and positioning error as low as 0.02 m for the temperature-influenced fiber segment. In the proposed demodulation method, the spatial resolution of temperature sensing is determined by the distribution of high backscattering points. The temperature sensing resolution depends on the spatial resolution of the OFDR system and the length of the temperature-influenced fiber. With an OFDR system spatial resolution of 12.5 µm, the temperature sensing resolution reaches 0.418 °C per meter of RBEF under test.


Assuntos
Dispositivos Ópticos , Temperatura , Sensação Térmica
7.
J Am Chem Soc ; 144(4): 1690-1699, 2022 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-35007085

RESUMO

Interest in developing antibacterial polymers as synthetic mimics of host defense peptides (HPDs) has accelerated in recent years to combat antibiotic-resistant bacterial infections. Positively charged moieties are critical in defining the antibacterial activity and eukaryotic toxicity of HDP mimics. Most examples have utilized primary amines or guanidines as the source of positively charged moieties, inspired by the lysine and arginine residues in HDPs. Here, we explore the impact of amine group variation (primary, secondary, or tertiary amine) on the antibacterial performance of HDP-mimicking ß-peptide polymers. Our studies show that a secondary ammonium is superior to either a primary ammonium or a tertiary ammonium as the cationic moiety in antibacterial ß-peptide polymers. The optimal polymer, a homopolymer bearing secondary amino groups, displays potent antibacterial activity and the highest selectivity (low hemolysis and cytotoxicity). The optimal polymer displays potent activity against antibiotic-resistant bacteria and high therapeutic efficacy in treating MRSA-induced wound infections and keratitis as well as low acute dermal toxicity and low corneal epithelial cytotoxicity. This work suggests that secondary amines may be broadly useful in the design of antibacterial polymers.


Assuntos
Aminas/química , Antibacterianos/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Peptídeos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Infecção dos Ferimentos/tratamento farmacológico , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Escherichia coli/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Ceratite/patologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Camundongos , Testes de Sensibilidade Microbiana , Peptídeos/química , Peptídeos/farmacologia , Polímeros/química , Infecções Estafilocócicas/microbiologia , Infecção dos Ferimentos/microbiologia
8.
J Transl Med ; 20(1): 188, 2022 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-35484565

RESUMO

BACKGROUND: Recent studies exploring the roles of invasion-metastasis associated miRNAs in gallbladder cancer (GBC) are limited. In the study, we aimed to identify the invasion-metastasis associated miRNAs in GBC by bioinformatics and experimental validation. METHODS: MiRNAs of different expression were identified by comparing GBC tumor samples with different survival from Gene Expression Omnibus database. MiRTarBase was used for identifying the potential target genes of miRNAs. Then, we performed Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. And miRNA-gene and protein-protein interaction (PPI) network were constructed for hub genes evaluation. We further explored and compared miR-642a-3p and miR-145-5p expression in both The Cancer Genome Atlas database and our hospital data. Finally, quantitative real-time PCR, wound healing assay, and Transwell assay were conducted to validate the invasion-metastasis associated miRNAs in GBC. RESULTS: In GSE104165 database, 25 up-regulated and 97 down-regulated miRNAs were detected with significantly different expression in GBC tumor samples. Then, 477 potential target genes were identified from the 2 most up-regulated miRNAs (miR-4430 and miR-642a-3p) and 268 genes from the 2 most down-regulated miRNAs (miR-451a and miR-145-5p). After GO and KEGG analysis, mTOR and PI3K-Akt signaling pathways were found associated with the potential target genes. Based on PPI network, the top 10 highest degree hub nodes were selected for hub genes. Furthermore, the miRNA-hub gene network showed significant miR-642a-3p up-regulation and miR-145-5p down-regulation in both GBC tissues and cell lines. In the experimental validation, miR-145-5p up-regulation and miR-642a-3p down-regulation were confirmed to suppress GBC invasion and metastasis. CONCLUSIONS: MiR-642a-3p and miR-145-5p were identified as invasion-metastasis associated miRNAs via bioinformatics and experimental validation, and both up-regulation of miR-642a-3p and down-regulation of miR-145-5p would be served as novel treatment options for GBC in the future.


Assuntos
Carcinoma in Situ , Neoplasias da Vesícula Biliar , MicroRNAs , Biologia Computacional , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/patologia , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/genética
9.
Opt Express ; 30(9): 14615-14616, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35473200

RESUMO

We correct several errors in our publication [Opt. Express30(4): 5347 (2022)10.1364/OE.452756].

10.
Opt Express ; 30(4): 5347-5359, 2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35209500

RESUMO

V-grooves are critical components for attaching fiber pigtails to photonics integrated circuits and for holding fibers in optical devices. Improper choice of V-groove angles and clamping method may cause large birefringence in the fibers and degrade polarization related performance of the devices. In this paper, we theoretically analyze the clamping-force induced birefringence of a single-mode (SM) fiber clamped in a V-groove by a flat-lid or by two identical V-grooves, respectively. We build a distributed polarization analyzer with complete Muller matrix analysis capability, which enables us to accurately measure local birefringence values in the fiber induced by clamped V-grooves of different angles. We find that for a SM fiber clamped in a commercial V-groove made with ZrO2 or SiO2 by a flat-lid, the zero-birefringence (ZB) angle is almost exactly 60°, suggesting that the friction coefficient in the V-groove can be safely ignored. In contrast, previous studies either indicated that the ZB V-groove angles clamped by a flat-lid never existed or significantly deviated from 60° due to the friction coefficient. More importantly, we also find, for the first time, both theoretically and experimentally, that a SM fiber clamped by two identical commercial V-grooves has a ZB when the V-groove angle is 90°. The methods and results reported in this paper shall prove beneficial for the fiber optic component industry to optimize polarization related performances of devices for sensing, communication, and instrumentation applications.

11.
Cell Commun Signal ; 20(1): 105, 2022 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-35842652

RESUMO

BACKGROUND: Penfluridol (PF) is an FDA-approved antipsychotic drug that has recently been shown to have anticancer activity. However, the anticancer effects and underlying mechanisms of PF are not well-established in gallbladder cancer (GBC). METHODS: The anticancer efficacy of PF on GBC was investigated via a series of cell functions experiments, including cell viability, colony formation, apoptosis assays, and so on. The corresponding signaling changes after PF treatment were explored by western blotting. Then, nude mice were utilized to study and test the anticancer activity of PF in vivo. Besides, glucose consumption and lactic production assays were used to detect the glycolysis alteration. RESULTS: In this study, we discovered that PF greatly inhibited the proliferation and invasion ability of GBC cells (GBCs). The glucose consumption and lactic generation ability of GBCs were dramatically elevated following PF treatment. Additionally, we discovered that inhibiting glycolysis could improve PF's anticancer efficacy. Further studies established that the activation of the AMPK/PFKFB3 signaling pathway medicated glycolysis after PF treatment. We proved mechanistically that inhibition of AMPK/PFKFB3 singling pathway mediated glycolysis was a potential synergetic strategy to improve the anticancer efficacy of PF on GBC. CONCLUSIONS: By inhibiting AMPK, the anticancer effects of PF on GBCs were amplified. As a result, our investigations shed new light on the possibility of repurposing PF as an anticancer drug for GBC, and AMPK inhibition in combination with PF may represent a novel therapeutic strategy for GBC. Video abstract.


Assuntos
Neoplasias da Vesícula Biliar , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/metabolismo , Glucose/metabolismo , Glicólise , Camundongos , Camundongos Nus , Penfluridol/farmacologia
12.
Langmuir ; 38(7): 2379-2391, 2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35148117

RESUMO

Membrane active compounds are able to induce various types of membrane perturbations. Natural or biomimetic candidates for antimicrobial treatment or drug delivery scenarios are mostly designed and tested for their ability to induce membrane permeabilization, also termed leakage. Furthermore, the interaction of these usually cationic amphiphiles with negatively charged vesicles often causes colloidal instability leading to vesicle aggregation or/and vesicle fusion. We show the interplay of these modes of membrane perturbation in mixed phosphatidyl glycerol (PG)/phosphatidyl ethanolamine (PE) by the statistical copolymer MM:CO comprising, both, charged and hydrophobic subunits. MM:CO is a representative of partially hydrophobic, highly active, but less selective antimicrobial polycations. Cryo-electron microscopy indicates vesicle fusion rather than vesicle aggregation upon the addition of MM:CO to negatively charged PG/PE (1:1) vesicles. In a combination of fluorescence-based leakage and fusion assays, there is support for membrane permeabilization and pronounced vesicle fusion activity as distinct effects. To this end, membrane fusion and aggregation were prevented by including lipids with polyethylene glycol attached to their head groups (PEG-lipids). The leakage activity of MM:CO is very similar in the absence and presence of PEG-lipids. Vesicle aggregation and fusion however are largely suppressed. This strongly suggests that MM:CO induces leakage by asymmetric packing stress because of hydrophobically driven interactions which could lead to leakage. As a further membrane perturbation effect, MM:CO causes lipid clustering in model vesicles. We address potential artifacts and misinterpretations of experiments characterizing leakage and fusion. Additional to the leakage activity, the pronounced fusogenic activity of the polymer and potentially of many other similar compounds likely has implications for antimicrobial activity and beyond.


Assuntos
Anti-Infecciosos , Fusão de Membrana , Anti-Infecciosos/farmacologia , Análise por Conglomerados , Microscopia Crioeletrônica , Polieletrólitos , Eletricidade Estática
13.
Ecotoxicol Environ Saf ; 239: 113638, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35597142

RESUMO

Recently, concerns for species that sex differentiation is influenced by temperature in the context of global warming have increased because disrupted operational sex ratios could threaten population maintenance. In contrast, little attention has been given to the reproductive ability of populations that experienced elevated temperatures. In this study, we demonstrated that high temperature (HT) would decrease population size via three different aspects of reproductive ability for the first time. We show that, in a thermo-sensitive teleost yellow catfish, a short period of HT (+3 °C) exposure during the critical period of sex differentiation leads to a different percentage of masculinization of XX genotypic females (1-23%) in wet-lab and natural water bodies. Combining the results of gonadal appearance, histology, sperm parameters, and fertilization rate, we found that XX pseudo-males induced by HT display significantly discounted fertility and reproductive performance compared to XY normal males. We demonstrate that the survival of the XY genotype is lower than XX genotype under environmental stress, including HT, hypoxia, and parasite infection, and the differential survival seems unrelated to male-biased sexual size dimorphism. The mathematical model predicts that the phenotypic female percent will be stabilized at 50% and the population will be sustainably maintained when masculinizing force is less than 0.5, while HT will put the population in danger when the masculinizing force exceeds 0.5. However, when we combine the real-world data of reproductive ability and mathematic model, our results suggest the population size decreases and the long-term survival of the studied species are threatened under the projected pace of increasing temperature. These findings will be useful for understanding the long-term effects of increasing temperature on sex ratio, reproduction and population maintenance in teleost.


Assuntos
Peixes-Gato , Processos de Determinação Sexual , Animais , Peixes-Gato/genética , Feminino , Masculino , Reprodução , Sêmen , Razão de Masculinidade , Temperatura
14.
Phys Chem Chem Phys ; 23(2): 1475-1488, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33399594

RESUMO

A promising alternative to classical antibiotics are antimicrobial peptides and their synthetic mimics (smAMPs) that supposedly act directly on membranes. For a more successful design of smAMPs, we need to know how the type of interaction with the membrane determines the type of membrane perturbation. How this, in turn, transfers into selectivity and microbial killing activity is largely unknown. Here, we characterize the action of two smAMPs: MM:CO (a copolymer of hydrophobic cyclooctyl subunits and charged ß-monomethyl-α-aminomethyl subunits) and the highly charged poly-NM (a homopolymer of α-aminomethyl subunits). By thorough characterization of vesicle leakage experiments, we elucidate complex membrane perturbation behavior in zwitterionic or negatively charged vesicles. Vesicle leakage data does not entirely agree with the growth inhibition of microbes. Our ensemble of advanced membrane permeabilization approaches clarifies these discrepancies. Long cumulative leakage kinetics show that the two smAMPs act either by transient leakage or by rare stochastic leakage events that occur at charge neutralization in the sample. We determine the strengths of individual leakage events induced by the smAMPs in membranes of various compositions. These strengths indicate changes in leakage mechanism over time and concentration range. Thus, our sophisticated analysis of vesicle leakage experiments reveals a fine-tuned flexibility in membrane permeabilization mechanisms. These details are indispensable in judging and designing membrane-active compounds.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Lipossomas Unilamelares/metabolismo , Peptídeos Catiônicos Antimicrobianos/química , Fluoresceínas/química , Glicerofosfatos/química , Interações Hidrofóbicas e Hidrofílicas , Permeabilidade/efeitos dos fármacos , Ligação Proteica , Eletricidade Estática , Lipossomas Unilamelares/química
15.
Int J Mol Sci ; 21(24)2020 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-33352639

RESUMO

Dengue virus (DENV) infection is a significant public health threat in tropical and subtropical regions; however, there is no specific antiviral drug. Accumulated studies have revealed that DENV infection induces several cellular responses, including autophagy and apoptosis. The crosstalk between autophagy and apoptosis is associated with the interactions among components of these two pathways, such as apoptotic caspase-mediated cleavage of autophagy-related proteins. Here, we show that DENV-induced autophagy inhibits early cell apoptosis and hence enhances DENV replication. Later, the apoptotic activities are elevated to suppress autophagy through cleavage of Beclin-1, an essential autophagy-related protein. Inhibition of cleavage of Beclin-1 by a pan-caspase inhibitor, Z-VAD, increases both autophagy and viral replication. Regarding the mechanism, we further found that DENV nonstructural protein 1 (NS1) is able to interact with Beclin-1 during DENV infection. The interaction between Beclin-1 and NS1 attenuates Beclin-1 cleavage and facilitates autophagy to prevent cell apoptosis. Our study suggests a novel mechanism whereby NS1 preserves Beclin-1 for maintaining autophagy to antagonize early cell apoptosis; however, elevated caspases trigger apoptosis by degrading Beclin-1 in the late stage of infection. These findings suggest implications for anti-DENV drug design.


Assuntos
Proteína Beclina-1/metabolismo , Caspases/metabolismo , Vírus da Dengue/isolamento & purificação , Dengue/patologia , Dengue/virologia , Proteínas não Estruturais Virais/metabolismo , Células A549 , Aedes , Animais , Autofagia , Dengue/metabolismo , Humanos
16.
Sci Rep ; 14(1): 13338, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858587

RESUMO

In order to investigate the effects of strain rate and water saturation on the energy dissipation and crack growth of tuff, uniaxial compression tests were carried out on dry and water saturated tuff with different strain rates using an electro-hydraulic servo press and a 50 mm diameter split Hopkinson pressure rod (SHPB) device. High-speed camera and Image J image analysis software were used to obtain the crack growth process of the specimen under impact load, and fractal dimension was introduced to quantitatively study the crack growth degree. The results show that more than 90% of the energy is stored in the specimen as elastic energy when it reaches the peak stress under static load. The average total energy of water-saturated specimens is 67.55% of that of dry specimens. The average energy dissipation density of water-saturated specimens under 0.3 MPa, 0.4 MPa and 0.5 MPa air pressure is 0.79, 0.91 and 0.92 times of that of dry specimens, respectively. Water-saturated specimens will deteriorate and thus reduce their energy storage and energy absorption effects. The reflected energy, transmitted energy, absorbed energy and incident energy are linear, logarithmic and linear functions, respectively, and the energy absorptivity and specific energy absorptivity of water-saturated specimens are lower than those of dry specimens. Due to the existence of "stefan" effect, the increase of energy dissipation density of water-saturated specimen at high strain rate is greater than that of dry specimen. The mean fractal dimension of water-saturated specimens under 0.3 MPa, 0.4 MPa and 0.5 MPa is 1.09, 1.05 and 1.16 times that of dry specimens. At the same strain rate, the number and width of cracks in water-saturated specimens are larger than that in dry specimens. Water-saturated behavior reduces the energy absorption capacity of tuff, increases the fractal dimension of crack growth, and significantly reduces the resistance of water-saturated rock to external loads.

17.
Medicine (Baltimore) ; 103(12): e37397, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38518028

RESUMO

RATIONALE: Vacuum sealing drainage is a novel technique for wound treatment that is characterized by adequate drainage and promotes wound healing. We report a case in which negative pressure sealing drainage was applied to treat a deep cervical abscess and achieved a good therapeutic effect. PATIENT CONCERNS: The abscess in the neck will go down. DIAGNOSES: Deep neck abscess. INTERVENTIONS: The usual surgical approach to treating this condition is to make a small incision to incise and drain the patient infected area where it is most visibly swollen or fluctuating, and to place a negative pressure drainage device. OUTCOMES: Eleven days after the operation, the patient neck recovered well, there was no infection in the operation area, and the patient was discharged from the hospital with improved symptoms. LESSONS: This proves that the negative pressure closed drainage technique has potential in the treatment of deep neck abscesses and is also an effective choice in promoting wound healing, which is expected to bring better therapeutic effects to patients treated for deep neck abscesses.


Assuntos
Tratamento de Ferimentos com Pressão Negativa , Humanos , Tratamento de Ferimentos com Pressão Negativa/métodos , Abscesso/cirurgia , Drenagem/métodos , Pescoço/cirurgia , Cicatrização , Resultado do Tratamento
18.
Respir Med ; 234: 107803, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39251097

RESUMO

OBJECTIVE: This study aimed to develop and validate a nomogram for predicting 28-day and 90-day mortality in intensive care unit (ICU) patients who have chronic obstructive pulmonary disease (COPD) coexisting with congestive heart failure (CHF). METHODS: An extensive analysis was conducted on clinical data from the Medical Information Mart for Intensive Care IV database, covering patients over 18 years old with both COPD and CHF, who were were first-time ICU admissions between 2008 and 2019. The least absolute shrinkage and selection operator (LASSO) regression method was employed to screen clinical features, with the final model being optimized using backward stepwise regression guided by the Akaike Information Criterion (AIC) to construct the nomogram. The predictive model's discrimination and clinical applicability were evaluated via receiver operating characteristic (ROC) curves, calibration curves, the C-index, and decision curve analysi s (DCA). RESULTS: This analysis was comprised of a total of 1948 patients. Patients were separated into developing and validation cohorts in a 7:3 ratio, with similar baseline characteristics between the two groups. The ICU mortality rates for the developing and verification cohorts were 20.8 % and 19.5 % at 28 days, respectively, and 29.4 % and 28.3 % at 90 days, respectively. The clinical characteristics retained by the backward stepwise regression include age, weight, systolic blood pressure (SBP), respiratory rate (RR), oxygen saturation (SpO2), red blood cell distribution width (RDW), lactate, partial thrombosis time (PTT), race, marital status, type 2 diabetes mellitus (T2DM), malignant cancer, acute kidney failure (AKF), pneumonia, immunosuppressive drugs, antiplatelet agents, vasoactive agents, acute physiology score III (APS III), Oxford acute severity of illness score (OASIS), and Charlson comorbidity index (CCI). We developed two separate models by assigning weighted scores to each independent risk factor: nomogram A excludes CCI but includes age, T2DM, and malignant cancer, while nomogram B includes only CCI, without age, T2DM, and malignant cancer. Based on the results of the AUC and C-index, this study selected nomogram A, which demonstrated better predictive performance, for subsequent validation. The calibration curve, C-index, and DCA results indicate that nomogram A has good accuracy in predicting short-term mortality and demonstrates better discriminative ability than commonly used clinical scoring systems, making it more suitable for clinical application. CONCLUSION: The nomogram developed in this study offers an effective assessment of short-term mortality risk for ICU patients with COPD and CHF, proving to be a superior tool for predicting their short-term prognosis.

19.
Sci Rep ; 14(1): 20566, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39232076

RESUMO

To investigate the effects of high temperature and carbon fiber-bar reinforcement on the dynamic mechanical properties of concrete materials, a muffle furnace was used to treat two kinds of specimens, plain and carbon fiber-bar reinforced concrete, at high temperatures of 25, 200, 400 and 600 °C. Impact compression tests were carried out on two specimens after high-temperature exposure using a Hopkinson pressure bar (SHPB) test setup combined with a high-speed camera device to observe the crack extension process of the specimens. The effects of high temperature and carbon fiber-bar reinforcement on the peak stress, energy dissipation density, crack propagation and fractal dimension of the concrete were analyzed. The results showed that the corresponding peak strengths of the plain concrete specimens at 25, 200, 400, and 600 °C were 88.37, 93.21, 68.85, and 54.90 MPa, respectively, and the peak strengths after the high-temperature exposure first increased slightly and then decreased rapidly. The mean peak strengths corresponding to the carbon fiber-bar reinforced concrete specimens after high-temperature action at 25, 200, 400, and 600 °C are 1.13, 1.13, 1.21, and 1.19 times that of plain concrete, respectively, and the mean crushing energy consumption densities are 1.27, 1.31, 1.73, and 1.59 times that of plain concrete, respectively. The addition of carbon fiber-bar reinforcement significantly enhanced the impact resistance and energy dissipation of the concrete structure, and the higher the temperature was, the more significant the increase. An increase in temperature increases the number of crack extensions and width, and the high tensile strength of the carbon fiber-bar reinforcement and the synergistic effect with the concrete material reduce the degree of crack extension in the specimen. The fractal dimension of the concrete ranged from 1.92 to 2.68, that of the carbon fiber-bar reinforced concrete specimens ranged from 1.61 to 2.42, and the mean values of the corresponding fractal dimensions of the plain concrete specimens after high-temperature effects at 25, 200, 400, and 600 °C were 1.19, 1.21, 1.10, and 1.11 times those of the fiber-reinforced concrete specimens, respectively. The incorporation of carbon fiber-bar reinforcement reduces the degree of rupture and fragmentation of concrete under impact loading and improves the safety and stability of concrete structures.

20.
Bioresour Technol ; 395: 130392, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38301943

RESUMO

Two laboratory-level biological aerated filters (BAF) were constructed to explore their treatment capacity for simulated antibiotic wastewater at high (1 - 16 mg/L) and low (0 - 0.5 mg/L) concentrations. Results showed that BAF was capable of removing both sulfonamides and tetracyclines with an efficiency of over 90 % at 16 mg/L. The main mechanism for removing antibiotics was found to be biodegradation followed by adsorption. Paenarthrobacter was identified as the key genus in sulfonamides degradation, while Hydrogenophaga played a crucial role in tetracyclines degradation. Antibiotics resistant genes such as intI1, sul1, sul2, tetA, tetW and tetX were frequently detected in the effluent, with interception rates ranging from 105 - 106 copies/mL. The dominated microorganisms obtained in the study could potentially be utilized to enhance the capacity of biological processes for treating antibiotics contaminated wastewater. These findings contribute to a better understanding of BAF treating wastewater containing antibiotics and resistant genes.


Assuntos
Antibacterianos , Águas Residuárias , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos/genética , Tetraciclinas , Sulfonamidas , Eliminação de Resíduos Líquidos
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