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1.
Surg Endosc ; 37(1): 391-401, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35982285

RESUMEN

BACKGROUND: To compare the traditional single-layer and double-layer suture renorrhaphy with modified "Binding" suture renorrhaphy (whole rim of the wound was closed by the all-layer flow suture starting from the parenchyma cut edges to hilum, followed by the final defect closure) in robotic partial nephrectomy (RPN) for treating localized renal cell carcinoma in our large institutional experience. METHODS: We retrospectively reviewed clinical data of 406 consecutive patients who underwent RPN from May 2018 and December 2020 in our center. The demographic and oncologic outcome variables were compared between different renal reconstruction groups and the effect of these suture techniques on renal function outcomes was also evaluated. RESULTS: For the single-layer group, median operative time and warm ischemic time were significantly less than that of the double-layer and "Binding" groups (p < 0.001), while the significantly lower eGFR drop (p = 0.014) was also detected within postoperative 3 months from baseline, but this difference lost its statistical significance from 3th month to the last follow-up. The changes in postoperative creatinine values were clinically insignificant among the three groups. In a sub-analysis over 258 patients with moderate/high nephrometry score, those patients who underwent "Binding" suture had an undifferentiated warm ischemic time, estimated blood loss, and length of hospitalization stay with a decreased risk of Grade III complications (postoperative hemorrhage requiring intervention) and improved renal function recovery during the whole follow-up. CONCLUSION: Single-layer suture renorrhaphy may be associated with better renal functional preservation and could prove to be reliable in patients with low-complexity tumor (RENAL score ≤ 6). Patients with moderate/high-complexity tumor (RENAL score ≥ 7) might represent a subgroup of patients having a functional benefit after "Binding" suture renorrhaphy even in the long-term period.


Asunto(s)
Neoplasias Renales , Procedimientos Quirúrgicos Robotizados , Humanos , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Procedimientos Quirúrgicos Robotizados/métodos , Estudios Retrospectivos , Nefrectomía/métodos , Riñón/cirugía , Riñón/patología , Resultado del Tratamiento
2.
Zhonghua Nan Ke Xue ; 29(12): 980-985, 2023 Dec.
Artículo en Zh | MEDLINE | ID: mdl-38639949

RESUMEN

OBJECTIVE: To investigate the expression and significance of GDF3 in testicular cancer through bioinformatics analysis. METHODS: Using the TCGA and GTEx databases, differential expression analysis and pan-cancer analysis were performed to identify the target gene GDF3, and the clinical relevance of GDF3 in testicular cancer was analyzed using the UALCAN database. Based on the R packages "org.Hs.eg.db" and "clusterProfiler," gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore the potential functions of GDF3 in testicular cancer. The correlation of GDF3 with immune chemokines and immune inhibitors in testicular cancer was investigated using the TISIDB database. RESULTS: The GDF3 was significantly upregulated in testicular cancer (P<0.001) and closely associated with clinical staging (P<0.05) and tumor subtypes (P<0.001). The immune-related analysis revealed that GDF3 was strongly correlated with immune chemokines CCL26 (rho=0.599, P<0.001), CCL7 (rho=0.525, P<0.001), immune inhibitor ADORA2A (rho=0.723, P<0.001), and PVRL2 (rho=0.585, P<0.001). CONCLUSION: The GDF3 is closely related to the occurrence, development, and immune microenvironment of testicular cancer.


Asunto(s)
Factor 3 de Diferenciación de Crecimiento , Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Humanos , Masculino , Quimiocinas , Biología Computacional , Neoplasias Testiculares/genética , Microambiente Tumoral , Factor 3 de Diferenciación de Crecimiento/genética
3.
Sensors (Basel) ; 20(11)2020 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-32485900

RESUMEN

Soluble solid content (SSC), pH, and vitamin C (VC) are considered as key parameters for strawberry quality. Spectral, color, and textural features from hyperspectral reflectance imaging of 400-1000 nm was to develop the non-destructive detection approaches for SSC, pH, and VC of strawberries by integrating various multivariate methods as partial least-squares regression (PLSR), support vector regression, and locally weighted regression (LWR). SSC, pH, and VC of 120 strawberries were statistically analyzed to facilitate the partitioning of data sets, which helped optimize the model. PLSR, with spectral and color features, obtained the optimal prediction of SSC with determination coefficient of prediction (Rp2) of 0.9370 and the root mean square error of prediction (RMSEP) of 0.1145. Through spectral features, the best prediction for pH was obtained by LWR with Rp2 = 0.8493 and RMSEP = 0.0501. Combination of spectral and textural features with PLSR provided the best results of VC with Rp2 = 0.8769 and RMSEP = 0.0279. Competitive adaptive reweighted sampling and uninformative variable elimination (UVE) were used to select important variables from the above features. Based on the important variables, the accuracy of SSC, pH, and VC prediction both gain the promotion. Finally, the distribution maps of SSC, pH, and VC over time were generated, and the change trend of three quality parameters was observed. Thus, the proposed method can nondestructively and accurately determine SSC, pH, and VC of strawberries and is expected to design and construct the simple sensors for the above quality parameters of strawberries.

4.
Int J Mol Sci ; 21(9)2020 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-32357546

RESUMEN

Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a progressive motor disease with no broadly effective treatment. However, most current therapies are based on symptoms rather than the underlying disease mechanisms. In this review, we describe potential therapeutic strategies based on known pathological biomarkers and related pathogenic processes. The three major conclusions from the current studies are summarized as follows: (i) for the drugs currently being tested in clinical trials; a weak connection was observed between drugs and SCA3/MJD biomarkers. The only two exceptions are the drugs suppressing glutamate-induced calcium influx and chemical chaperon. (ii) For most of the drugs that have been tested in animal studies, there is a direct association with pathological biomarkers. We further found that many drugs are associated with inducing autophagy, which is supported by the evidence of deficient autophagy biomarkers in SCA3/MJD, and that there may be more promising therapeutics. (iii) Some reported biomarkers lack relatively targeted drugs. Low glucose utilization, altered amino acid metabolism, and deficient insulin signaling are all implicated in SCA3/MJD, but there have been few studies on treatment strategies targeting these abnormalities. Therapeutic strategies targeting multiple pathological SCA3/MJD biomarkers may effectively block disease progression and preserve neurological function.


Asunto(s)
Biomarcadores/metabolismo , Marcadores Genéticos , Enfermedad de Machado-Joseph/tratamiento farmacológico , Autofagia , Ensayos Clínicos como Asunto , Marcadores Genéticos/efectos de los fármacos , Humanos , Enfermedad de Machado-Joseph/genética , Enfermedad de Machado-Joseph/metabolismo , Terapia Molecular Dirigida , Transducción de Señal/efectos de los fármacos
5.
Int J Mol Sci ; 21(12)2020 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-32575820

RESUMEN

Although butylidenephthalide (BP) is an efficient anticancer drug, its poor bioavailability renders it ineffective for treating drug-resistant brain tumors. However, this problem is overcome through the use of noninvasive delivery systems, including intranasal administration. Herein, the bioavailability, drug stability, and encapsulation efficiency (EE, up to 95%) of BP were improved by using cyclodextrin-encapsulated BP in liposomal formulations (CDD1). The physical properties and EE of the CDD1 system were investigated via dynamic light scattering, transmission electron microscopy, UV-Vis spectroscopy, and nuclear magnetic resonance spectroscopy. The cytotoxicity was examined via MTT assay, and the cellular uptake was observed using fluorescence microscopy. The CDD1 system persisted for over 8 h in tumor cells, which was a considerable improvement in the retention of the BP-containing cyclodextrin or the BP-containing liposomes, thereby indicating a higher BP content in CDD1. Nanoscale CDD1 formulations were administered intranasally to nude mice that had been intracranially implanted with temozolomide-resistant glioblastoma multiforme cells, resulting in increased median survival time. Liquid chromatography-mass spectrometry revealed that drug biodistribution via intranasal delivery increased the accumulation of BP 10-fold compared to oral delivery methods. Therefore, BP/cyclodextrin/liposomal formulations have potential clinical applications for treating drug-resistant brain tumors.


Asunto(s)
Antineoplásicos/farmacocinética , Encéfalo/metabolismo , Sistemas de Liberación de Medicamentos , Anhídridos Ftálicos/farmacocinética , Animales , Antineoplásicos/administración & dosificación , Disponibilidad Biológica , Encéfalo/efectos de los fármacos , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Ciclodextrinas/química , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Liposomas/química , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Anhídridos Ftálicos/administración & dosificación , Distribución Tisular
6.
Anaerobe ; 60: 102094, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31499177

RESUMEN

It is known that antibiotic usage is associated with the development of Clostridioides difficile infection (CDI), especially clindamycin, third-generation cephalosporins, and fuoroquinolones. Antibiotic resistance rates to many antibiotics varies a lot by study. We performed a study focused on antibiotic resistance in clinical isolates of C. difficile from more widespread geographic regions across China. Of 319 C. difficile isolates tested against 11 antibiotics, 313 (98.1%) were resistant to at least one antibiotic. The highest rate of resistance was to ciprofloxacin, clindamycin, and erythromycin across all age groups, similar to previous studies. However, all isolates were susceptible to metronidazole and vancomycin. Overall the resistance rate to tested antibiotics was lower than other reports in China except for chloramphenicol and meropenem. Genotype ST37/RT017 in clade 4 was resistant to more antibiotics than other types. Unexpectedly, RT078 isolates in this study were susceptible to almost all tested antibiotics. In addition, the proportion of multi-drug resistant (MDR) isolates observed (17%) in this study was much lower than several European studies (up to 55%) and a previous study in China (78%). Although isolates from patients aged between 65 and 85 were more resistant to antibiotics in comparison to other age groups, MDR isolates were still detected in children below 2-years of age. The highest percentage of MDR isolates was determined in South China, an area that is most developed economically. The clade 4, RT017 (ST37) has been associated with outbreaks in Europe and North America and is responsible for most C. difficile infections (CDIs) in Asia. In addition, RT017 is often clindamycin and fluoroquinolone resistant. This study provided a relatively comprehensive description of antibiotic resistance of C. difficile in China, and further elucidates the epidemiology and antibiotic resistance of clinical isolates of C. difficile in China at a national level.


Asunto(s)
Antibacterianos/farmacología , Clostridioides difficile/efectos de los fármacos , Infecciones por Clostridium/epidemiología , Infecciones por Clostridium/microbiología , Farmacorresistencia Bacteriana , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Toxinas Bacterianas/genética , Niño , Preescolar , China/epidemiología , Clostridioides difficile/clasificación , Clostridioides difficile/genética , Clostridioides difficile/aislamiento & purificación , Farmacorresistencia Bacteriana Múltiple , Genotipo , Geografía Médica , Humanos , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Epidemiología Molecular , Vigilancia en Salud Pública , Ribotipificación , Adulto Joven
7.
Molecules ; 24(9)2019 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-31052245

RESUMEN

Pesticide residue detection is a hot issue in the quality and safety of agricultural grains. A novel method for accurate detection of pirimiphos-methyl residues in wheat was developed using surface-enhanced Raman spectroscopy (SERS) and chemometric methods. A simple pretreatment method was conducted to extract pirimiphos-methyl residue from wheat samples, and highly effective gold nanorods were prepared for SERS measurement. Raman peaks assignment was calculated using density functional theory. The Raman signal of pirimiphos-methyl can be detected when the concentrations of residue in wheat extraction solution and contaminated wheat is as low as 0.2 mg/L and 0.25 mg/L, respectively. Quantification of pirimiphos-methyl was performed by applying regression models developed by partial least squares regression, support vector machine regression and random forest with principal component analysis using different preprocessed methods. As for the contaminated wheat samples, the relative deviation between gas chromatography-mass spectrometry value and predicted value is in the range of 0.10%-6.63%, and predicted recovery is 94.12%-106.63%, ranging from 23.93 mg/L to 0.25 mg/L. Results demonstrated that the proposed SERS method is an effective and efficient analytical tool for detecting pirimiphos-methyl in wheat with high accuracy and excellent sensitivity.


Asunto(s)
Compuestos Organotiofosforados/química , Espectrometría Raman , Triticum/química , Cromatografía de Gases y Espectrometría de Masas , Estructura Molecular , Compuestos Organotiofosforados/análisis , Reproducibilidad de los Resultados , Espectrometría Raman/métodos
8.
Molecules ; 24(22)2019 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-31752262

RESUMEN

Fibrosis is a type of chronic organ failure, resulting in the excessive secretion of extracellular matrix (ECM). ECM protects wound tissue from infection and additional injury, and is gradually degraded during wound healing. For some unknown reasons, myofibroblasts (the cells that secrete ECM) do not undergo apoptosis; this is associated with the continuous secretion of ECM and reduced ECM degradation even during de novo tissue formation. Thus, matrix metalloproteinases (MMPs) are considered to be a potential target of fibrosis treatment because they are the main groups of ECM-degrading enzymes. However, MMPs participate not only in ECM degradation but also in the development of various biological processes that show the potential to treat diseases such as stroke, cardiovascular diseases, and arthritis. Therefore, treatment involving the targeting of MMPs might impede typical functions. Here, we evaluated the links between these MMP functions and possible detrimental effects of fibrosis treatment, and also considered possible approaches for further applications.


Asunto(s)
Fibrosis/etiología , Fibrosis/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Metaloproteinasas de la Matriz/farmacología , Animales , Susceptibilidad a Enfermedades , Activación Enzimática , Matriz Extracelular/metabolismo , Fibrosis/tratamiento farmacológico , Regulación de la Expresión Génica , Humanos , Inmunomodulación , Metaloproteinasas de la Matriz/genética , Metaloproteinasas de la Matriz/uso terapéutico , Miofibroblastos/metabolismo , Neovascularización Patológica , Especificidad de Órganos/genética , Proteolisis , Cicatrización de Heridas
9.
Langmuir ; 34(30): 9036-9046, 2018 07 31.
Artículo en Inglés | MEDLINE | ID: mdl-29986585

RESUMEN

Hanatoxin (HaTx) from spider venom works as an inhibitor of Kv2.1 channels, most likely by interacting with the voltage sensor (VS). However, the way in which this water-soluble peptide modifies the gating remains poorly understood as the VS is deeply embedded within the bilayer, although it would change its position depending on the membrane potential. To determine whether HaTx can indeed bind to the VS, the depth at which HaTx penetrates into the POPC membranes was measured with neutron reflectivity. Our results successfully demonstrate that HaTx penetrates into the membrane hydrocarbon core (∼9 Šfrom the membrane surface), not lying on the membrane-water interface as reported for another voltage sensor toxin (VSTx). This difference in penetration depth suggests that the two toxins fix the voltage sensors at different positions with respect to the membrane normal, thereby explaining their different inhibitory effects on the channels. In particular, results from MD simulations constrained by our penetration data clearly demonstrate an appropriate orientation for HaTx to interact with the membranes, which is in line with the biochemical information derived from stopped-flow analysis through delineation of the toxin-VS binding interface.

10.
Biochim Biophys Acta Biomembr ; 1859(5): 917-923, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28143758

RESUMEN

Hanatoxin (HaTx), a 35-residue polypeptide from spider venom, functions as an inhibitor of Kv2.1 channels by interacting with phospholipids prior to affecting the voltage-sensor. However, how this water-soluble peptide modifies the gating remains poorly understood, as the voltage-sensor is deeply embedded within the bilayer. To determine how HaTx interacts with phospholipid bilayers, in this study, we examined the toxin-induced partitioning of liposomal membranes. HPLC-results from high-speed spin-down vesicles with HaTx demonstrated direct binding. Dynamic light scattering (DLS) and leakage assay results further indicated that neither membrane pores nor membrane fragmentations were observed in the presence of HaTx. To clarify the binding details, Langmuir trough experiments were performed with phospholipid monolayers by mimicking the external leaflet of membrane bilayers, indicating the involvement of acyl chains in such interactions between HaTx and phospholipids. Our current study thus describes the interaction pattern of HaTx with vesicle membranes, defining a membrane-partitioning mechanism for peptide insertion involving the membrane hydrocarbon core without pore formation.


Asunto(s)
Membrana Dobles de Lípidos/química , Péptidos/química , Fosfolípidos/química , 1,2-Dipalmitoilfosfatidilcolina/química , Luz , Dispersión de Radiación
11.
Langmuir ; 33(11): 2885-2889, 2017 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-28260386

RESUMEN

Membrane perturbation induced by cysteine-rich peptides is a crucial biological phenomenon but scarcely investigated, in particular with effective biophysical-chemical methodologies. Hanatoxin (HaTx), a 35-residue polypeptide from spider venom, works as an inhibitor of drk1 (Kv2.1) channels, most likely by interacting with the voltage-sensor. However, how this water-soluble peptide modifies the gating remains poorly understood, as the voltage sensor was proposed to be deeply embedded within the bilayer. To see how HaTx interacts with phospholipid bilayers, we observe the toxin-induced perturbation on POPC/DOPG-membranes through measurements of the change in membrane thickness. Lamellar X-ray diffraction (LXD) was applied on stacked planar bilayers in the near-fully hydrated state. The results provide quantitative evidence for the membrane thinning in a concentration-dependent manner, leading to novel and direct combinatory approaches by discovering how to investigate such a biologically relevant interaction between gating-modifier toxins and phospholipid bilayers.


Asunto(s)
Péptidos/química , Difracción de Rayos X/métodos , Fosfatidilcolinas/química , Fosfatidilgliceroles/química , Venenos de Araña/química
12.
Mycopathologia ; 182(5-6): 459-469, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28084573

RESUMEN

Adhesion and biofilm formation, which can occur on abiotic and biotic surfaces, are key components in Candida pathogenicity. The aims of this study were to infer about the C. tropicalis clinical isolates ability to adhere and form biofilm on abiotic and biotic surfaces and to correlate that with the multilocus sequence typing and other virulence factors. Adhesion and biofilm formation were measured in 68 C. tropicalis isolates from 3 hospitals in China on abiotic (polystyrene) and biotic (human urinary bladder epithelial cell) surfaces by crystal violet assay and 2,3-bis (2-methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide reduction assay. In our study, almost all C. tropicalis isolates could adhere and produce biofilm on abiotic and biotic surfaces in a strain-dependent manner. The isolates from blood showed relatively lower adhesion and biofilm capacity on polystyrene surface, but had strong secreted aspartyl proteinase activity. Moreover, significant differences were found among MLST groups for adhesion and biofilm capacity. C. tropicalis in multilocus sequence typing group5 and group6 showed high adhesion and biofilm, while isolates in group1 exhibited low adhesion and biofilm formation. Overall, it is important to note that C. tropicalis isolates adhere to and produce biofilm on abiotic and biotic surfaces with strain specificity. These data will play an important role in subsequent research on the pathogenesis of C. tropicalis.


Asunto(s)
Biopelículas/crecimiento & desarrollo , Candida tropicalis/aislamiento & purificación , Candidiasis/microbiología , Adhesión Celular , Genotipo , Tipificación de Secuencias Multilocus , Técnicas de Tipificación Micológica , Candida tropicalis/clasificación , Candida tropicalis/genética , Candida tropicalis/fisiología , China , Humanos
13.
BMC Microbiol ; 14: 245, 2014 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-25410579

RESUMEN

BACKGROUND: Candida tropicalis is considered to be the leading pathogen causing nosocomial fungemia and hepatosplenic fungal infections in patients with cancer, particularly those with leukemia. Microsatellite-based typing methods using sets of genetic markers have been developed and reported for population structure analysis of C. albicans, C. glabrata, and C. parapsilosis, but no studies have been published for genetic analysis of C. tropicalis. The objective of this study was to develop new microsatellite loci that have the ability to distinguish among C. tropicalis isolates. RESULTS: DNA sequences containing over 10 bi- or tri-nucleotide repeats were selected from the C. tropicalis genome database. Thirty PCR primers sets specific for the microsatellite loci were designed and tested using eight clinically independent isolates. According to the amplification efficiency, specificity, and observed polymorphisms, eight markers were selected for further population structure analysis and molecular typing. Sixty-five independent C. tropicalis isolates were genotyped using these 8 markers. Based on these analyses, six microsatellite loci were confirmed, although two loci were found to be with unstable flanking areas. The six polymorphic loci displayed 4-22 alleles and 7-27 genotypes. The discriminatory power of the six loci ranged from 0.70 to 0.95. Genotyping results obtained by microsatellite analysis were compared to PCR-fingerprinting and multi-locus sequence typing (MLST). The comparisons showed that microsatellite analysis and MLST had the similar discriminatory power for C. tropicalis, which were more powerful than PCR-fingerprinting. CONCLUSIONS: This is the first attempt to develop new microsatellite loci for C. tropicalis. These newly developed markers will be a valuable resource for the differentiation of C. tropicalis isolates. More C. tropicalis isolates will need to be sequenced and analyzed in order to fully show the potential of these newly developed microsatellite markers.


Asunto(s)
Candida tropicalis/clasificación , Candida tropicalis/genética , Repeticiones de Microsatélite , Tipificación Molecular/métodos , Técnicas de Tipificación Micológica/métodos , Adulto , Alelos , Candida tropicalis/aislamiento & purificación , Candidiasis/microbiología , Cartilla de ADN/genética , ADN de Hongos/genética , Femenino , Variación Genética , Genotipo , Humanos , Masculino , Reacción en Cadena de la Polimerasa
14.
Toxicol Appl Pharmacol ; 278(3): 249-58, 2014 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-24823293

RESUMEN

DNA damage has been shown to induce autophagy, but the role of autophagy in the DNA damage response and cell fate is not fully understood. BO-1012, a bifunctional alkylating derivative of 3a-aza-cyclopenta[a]indene, is a potent DNA interstrand cross-linking agent with anticancer activity. In this study, BO-1012 was found to reduce DNA synthesis, inhibit S phase progression, and induce phosphorylation of histone H2AX on serine 139 (γH2AX) exclusively in S phase cells. Both CHK1 and CHK2 were phosphorylated in response to BO-1012 treatment, but only depletion of CHK1, but not CHK2, impaired BO-1012-induced S phase arrest and facilitated the entry of γH2AX-positive cells into G2 phase. CHK1 depletion also significantly enhanced BO-1012-induced cell death and apoptosis. These results indicate that BO-1012-induced S phase arrest is a CHK1-dependent pro-survival response. BO-1012 also resulted in marked induction of acidic vesicular organelle (AVO) formation and microtubule-associated protein 1 light chain 3 (LC3) processing and redistribution, features characteristic of autophagy. Depletion of ATG7 or co-treatment of cells with BO-1012 and either 3-methyladenine or bafilomycin A1, two inhibitors of autophagy, not only reduced CHK1 phosphorylation and disrupted S phase arrest, but also increased cleavage of caspase-9 and PARP, and cell death. These results suggest that cells initiate S phase arrest and autophagy as pro-survival responses to BO-1012-induced DNA damage, and that suppression of autophagy enhances BO-1012-induced apoptosis via disruption of CHK1-dependent S phase arrest.


Asunto(s)
Antineoplásicos Alquilantes/farmacología , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Carcinoma/tratamiento farmacológico , Sinergismo Farmacológico , Inhibidores Enzimáticos/farmacología , Proteínas Quinasas/metabolismo , Antineoplásicos Alquilantes/agonistas , Proteína 7 Relacionada con la Autofagia , Carbamatos/agonistas , Carbamatos/farmacología , Carcinoma/enzimología , Carcinoma/metabolismo , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1) , Fosfatidilinositol 3-Quinasas Clase III/antagonistas & inhibidores , Fosfatidilinositol 3-Quinasas Clase III/metabolismo , Reactivos de Enlaces Cruzados/farmacología , Femenino , Silenciador del Gen , Células HeLa , Compuestos Heterocíclicos con 3 Anillos/agonistas , Compuestos Heterocíclicos con 3 Anillos/farmacología , Humanos , Indenos/agonistas , Indenos/farmacología , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Fosforilación/efectos de los fármacos , Proteínas Quinasas/química , Proteínas Quinasas/genética , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Fase S/efectos de los fármacos , Enzimas Activadoras de Ubiquitina/antagonistas & inhibidores , Enzimas Activadoras de Ubiquitina/genética , Enzimas Activadoras de Ubiquitina/metabolismo , ATPasas de Translocación de Protón Vacuolares/antagonistas & inhibidores , ATPasas de Translocación de Protón Vacuolares/metabolismo
15.
Int J Biol Macromol ; 275(Pt 2): 133690, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38971280

RESUMEN

In pursuing sustainable thermal insulation solutions, this study explores the integration of human hair and feather keratin with alginate. The aim is to assess its potential in thermal insulation materials, focusing on the resultant composites' thermal and mechanical characteristics. The investigation uncovers that the type and proportion of keratin significantly influence the composites' porosity and thermal conductivity. Specifically, higher feather keratin content is associated with lesser sulfur and reduced crosslinking due to shorter amino acids, leading to increased porosity and pore sizes. This, in turn, results in a decrease in ß-structured hydrogen bond networks, raising non-ordered protein structures and diminishing thermal conductivity from 0.044 W/(m·K) for pure alginate matrices to between 0.033 and 0.038 W/(m·K) for keratin-alginate composites, contingent upon the specific ratio of feather to hair keratin used. Mechanical evaluations further indicate that composites with a higher ratio of hair keratin exhibit an enhanced compressive modulus, ranging from 60 to 77 kPa, demonstrating the potential for tailored mechanical properties to suit various applications. The research underscores the critical role of sulfur content and the crosslinking index within keratin's structures, significantly impacting the thermal and mechanical properties of the matrices. The findings position keratin-based composites as environmentally friendly alternatives to traditional insulation materials.

16.
Drug Deliv Transl Res ; 14(7): 1940-1953, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38161195

RESUMEN

A patient-friendly and efficient treatment method for patients with spinocerebellar ataxia type 3 (SCA3) was provided through a nose-to-brain liposomal system. Initially, PGK1 was overexpressed in HEK 293-84Q-GFP diseased cells (HEK 293-84Q-GFP-PGK1 cells) to confirm its effect on the diseased protein polyQ. A decrease in polyQ expression was demonstrated in HEK 293-84Q-GFP-PGK1 cells compared to HEK 293-84Q-GFP parental cells. Subsequently, PGK1 was encapsulated in a liposomal system to evaluate its therapeutic efficiency in SCA3. The optimized liposomes exhibited a significantly enhanced positive charge, facilitating efficient intracellular protein delivery to the cells. The proteins were encapsulated within the liposomes using an optimized method involving a combination of heat shock and sonication. The liposomal system was further demonstrated to be deliverable to the brain via intranasal administration. PGK1/liposomes were intranasally delivered to SCA3 mice, which subsequently exhibited an amelioration of motor impairment, as assessed via the accelerated rotarod test. Additionally, fewer shrunken morphology Purkinje cells and a reduction in polyQ expression were observed in SCA3 mice that received PGK1/liposomes but not in the untreated, liposome-only, or PGK1-only groups. This study provides a non-invasive route for protein delivery and greater delivery efficiency via the liposomal system for treating neurodegenerative diseases.


Asunto(s)
Administración Intranasal , Encéfalo , Liposomas , Enfermedad de Machado-Joseph , Fosfoglicerato Quinasa , Animales , Humanos , Fosfoglicerato Quinasa/genética , Encéfalo/metabolismo , Células HEK293 , Enfermedad de Machado-Joseph/tratamiento farmacológico , Enfermedad de Machado-Joseph/genética , Ratones , Péptidos/administración & dosificación , Péptidos/química
17.
Food Sci Nutr ; 12(1): 116-130, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38268910

RESUMEN

Osteoporosis is characterized by low bone mass, bone microarchitecture disruption, and collagen loss, leading to increased fracture risk. In the current study, collagen peptides were extracted from milkfish scales (MS) to develop potential therapeutic candidates for osteoporosis. MS was used to synthesize a crude extract of fish scales (FS), collagen liquid (COL), and hydroxyapatite powder (HA). COL samples were further categorized according to the peptide size of total COL (0.1 mg/mL), COL < 1 kDa (0.1 mg/mL), COL: 1-10 kDa (0.1 mg/mL), and COL > 10 kDa (0.1 mg/mL) to determine it. Semi-quantitative reverse transcription polymerase chain reaction (sqRT-PCR) and immunofluorescence labeling were used to assess the expression levels of specific mRNA and proteins in vitro. For in vivo studies, mice ovariectomy (OVX)-induced postmenopausal osteoporosis were developed, while the sham surgery (Sham) group was treated as a control. Collagen peptides (CP) from MS inhibited osteoclast differentiation in RAW264.7 cells following an insult with nuclear factor kappa-B ligand (RANKL). CP also enhanced osteoblast proliferation in MG-63 cells, possibly through downregulating NFATc1 and TRAP mRNA expression and upregulating ALP and OPG mRNA levels. Furthermore, COL1 kDa also inhibited bone density loss in osteoporotic mice. Taken together, CP may reduce RANKL-induced osteoclast activity while promoting osteoblast synthesis, and therefore may act as a potential therapeutic agent for the prevention and control of osteoporosis.

18.
Biomater Adv ; 156: 213722, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38101076

RESUMEN

Noninvasive lung drug delivery is critical for treating respiratory diseases. Pluronic-based copolymers have been used as multifunctional materials for medical and biological applications. However, the Pluronic F127-based hydrogel is rapidly degraded, adversely affecting the mechanical stability for prolonged drug release. Therefore, this study designed two thermosensitive copolymers by modifying the Pluronic F127 terminal groups with carboxyl (ADF127) or amine groups (EDF127) to improve the viscosity and storage modulus of drug formulations. ß-alanine and ethylenediamine were conjugated at the terminal of Pluronic F127 using a two-step acetylation process, and the final copolymers were characterized using 1H nuclear magnetic resonance (1H NMR) and Fourier-transform infrared spectra. According to the 1H NMR spectra, Pluronic F127 was functionalized to form ADF127 and EDF127 with 85 % and 71 % functionalization degrees, respectively. Rheological studies revealed that the ADF127 (15 wt%) and EDF127 (15 wt%) viscosities increased from 1480 Pa.s (Pluronic F127) to 1700 Pa.s and 1800 Pa.s, respectively. Furthermore, the elastic modulus of ADF127 and EDF127 increased, compared with that of native Pluronic F127 with the addition of 5 % mucin, particularly for ADF127, thereby signifying the stronger adhesive nature of ADF127 and EDF127 with mucin. Additionally, ADF127 and EDF127 exhibited a decreased gelation temperature, decreasing from 33 °C (Pluronic F127 at 15 wt%) to 24 °C. Notably, the in vitro ADF127 and EDF127 drug release was prolonged (95 %; 48 h) by the hydrogel encapsulation of the liposome-Bdph combined with mucin, and the intermolecular hydrogen bonding between the mucin and the hydrogel increased the retention time and stiffness of the hydrogels. Furthermore, ADF127 and EDF127 incubated with NIH-3T3 cells exhibited biocompatibility within 2 mg/mL, compared with Pluronic F127. The nasal administration method was used to examine the biodistribution of the modified hydrogel carrying liposomes or exosomes with fluorescence using the IVIS system. Drug accumulation in the lungs decreased in the following order: ADF127 > EDF127 > liposomes or exosomes alone. These results indicated that the carboxyl group-modified Pluronic F127 enabled well-distributed drug accumulation in the lungs, which is beneficial for intranasal administration routes in treating diseases such as lung fibrosis.


Asunto(s)
Liposomas , Poloxámero , Ratones , Animales , Poloxámero/química , Hidrogeles , Mucinas , Distribución Tisular , Polímeros , Pulmón
20.
Research (Wash D C) ; 6: 0059, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36951796

RESUMEN

The lack of efficient crop phenotypic measurement methods has become a bottleneck in the field of breeding and precision cultivation. However, high-throughput and accurate phenotypic measurement could accelerate the breeding and improve the existing cultivation management technology. In view of this, this paper introduces a high-throughput crop phenotype measurement platform named the LQ-FieldPheno, which was developed by China National Agricultural Information Engineering Technology Research Centre. The proposed platform represents a mobile phenotypic high-throughput automatic acquisition system based on a field track platform, which introduces the Internet of Things (IoT) into agricultural breeding. The proposed platform uses the crop phenotype multisensor central imaging unit as a core and integrates different types of equipment, including an automatic control system, upward field track, intelligent navigation vehicle, and environmental sensors. Furthermore, it combines an RGB camera, a 6-band multispectral camera, a thermal infrared camera, a 3-dimensional laser radar, and a deep camera. Special software is developed to control motions and sensors and to design run lines. Using wireless sensor networks and mobile communication wireless networks of IoT, the proposed system can obtain phenotypic information about plants in their growth period with a high-throughput, automatic, and high time sequence. Moreover, the LQ-FieldPheno has the characteristics of multiple data acquisition, vital timeliness, remarkable expansibility, high-cost performance, and flexible customization. The LQ-FieldPheno has been operated in the 2020 maize growing season, and the collected point cloud data are used to estimate the maize plant height. Compared with the traditional crop phenotypic measurement technology, the LQ-FieldPheno has the advantage of continuously and synchronously obtaining multisource phenotypic data at different growth stages and extracting different plant parameters. The proposed platform could contribute to the research of crop phenotype, remote sensing, agronomy, and related disciplines.

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