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2.
Chem Commun (Camb) ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38963238

RESUMEN

The versatile reactivity of isothiocyanate intermediates enabled the diversity-oriented synthesis (DOS) of N-heterocycles in a DNA-compatible manner. We first reported a mild in situ conversion of DNA-conjugated amines to isothiocyanates. Subsequently, a set of diverse transformations was successfully developed to construct 2-thioxo-quinazolinones, 1,2,4-thiadiazoles, and 2-imino thiazolines. Finally, the feasibility of these approaches in constructing DELs was further demonstrated through enzymatic ligation and mock pool preparation. This study demonstrated the advantages of combining in situ conversion strategies with DOS, which effectively broadened the chemical and structural diversity of DELs.

3.
Am J Cancer Res ; 14(6): 2984-2993, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39005674

RESUMEN

This study aimed to define the role of heterogeneity of liver parenchymal enhancement on computed tomography (CT) in the survival of patients with hepatocellular carcinoma (HCC) after hepatic resection. The medical records of patients with HCCs and who had undergone hepatic resection were retrospectively reviewed. The standard deviation (SD) of three different enhanced CT scan images was used to estimate the heterogeneity of liver parenchymal enhancement: SD of > 5.6, heterogenous enhancement, and SD of ≤ 5.6, homogeneous enhancement. A total of 57 patients had heterogenous enhancement, and 143 patients had homogeneous enhancement. The patients with heterogenous enhancement had longer disease-free and overall survivals than those with other enhancements (log-rank test, P < 0.001 and P = 0.036). The pathologic exam showed that heterogenous enhancement tended to develop septa in the peritumoral liver tissues. The prevalence of CD8+ cells was significantly higher in the peritumor liver tissues with septa than in those without (0.83% vs. 0.26%, P < 0.001). The peritumoral CD8/Foxp3 ratio was higher in the liver tissues with septa than in those without (1.22 vs. 0.47, P = 0.001), and patients with CD8/Foxp3 of > 0.8 had better overall survival than those with CD8/Foxp3 of ≤ 0.8 (log-rank test, P = 0.028). In conclusion, patients who had undergone hepatic resection with a heterogenous liver parenchymal enhancement tended to develop hepatic septa, which was associated with a higher CD8/Foxp3 ratio and longer survival. Therefore, contrast-enhanced CT scans might be a useful tool to predict the outcome of HCC.

4.
Bioorg Chem ; 150: 107571, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38936048

RESUMEN

In recent years, Varicocele (VC) has been recognized as a common cause of male infertility that can be treated by surgery or drugs. How to reduce the damage of VC to testicular spermatogenic function has attracted extensive attention in recent years. Among them, overexpressed ROS and high levels of inflammation may play a key role in VC-induced testicular damage. As the key mediated innate immune pathways, cGAS-STING shaft under pathological conditions, such as in cell and tissue damage stress can be cytoplasmic DNA activation, induce the activation of NLRP3 inflammatory corpuscle, triggering downstream of the inflammatory cascade reaction. Chlorogenic acid (CGA), as a natural compound from a wide range of sources, has strong anti-inflammatory and antioxidant activities, and is a potential effective drug for the treatment of varicocele infertility. The aim of this study is to investigate the role of CGA in the spermatogenic dysfunction of the rat testis induced by VC and the potential mechanisms. The results of this study have shown that CGA gavage treatment ameliorated the pathological damage of seminiferous tubules, increased the number of sperm in the lumen, and increased the expression levels of Occludin and ZO-1, which indicated the therapeutic effect of CGA on spermatogenic dysfunction in the testis of VC rats. Meanwhile, the damage of mitochondrial structure was alleviated and the expression levels of ROS, NLRP3 and pro-inflammatory cytokines (IL-1ß, IL-6, IL-18) were significantly reduced in the testicular tissues of model rats after CGA treatment. In addition, we demonstrated for the first time the high expression status of cGAS and STING in testicular tissues of VC model rats, and this was ameliorated to varying degrees after CGA treatment. In conclusion, this study suggests that CGA can improve the spermatogenic function of the testis by reducing mitochondrial damage and inhibiting the activation of the cGAS-STING axis, inhibiting the activation of the NLRP3 inflammasome, and improving the inflammatory damage of the testis, highlighting the potential of CGA as a therapeutic agent for varicocele infertility.

5.
Respirol Case Rep ; 12(6): e01391, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38831800

RESUMEN

Odontogenic infections can spread to the respiratory tract. Despite the known role of Tannerella forsythia as the primary pathogen in periodontitis, the association between T. forsythia infection and risk of pneumonia or lung abscess remains unknown. In this report, we present a case of lung abscess caused by T. forsythia infection. The pathogen was detected by metagenomic next-generation sequencing (mNGS) in the bronchoalveolar lavage fluid of the patient. The clinical characteristics and possible mechanisms of the infection are discussed. T. forsythia is a conditional pathogen that can cause lung abscess in the presence of helper bacteria and reduced host immune status. The course of treatment should be personalized and might be longer than 3 months.

6.
Front Immunol ; 15: 1380229, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38911867

RESUMEN

Background: Vitamin E, which is also known as tocopherol, is a compound with a polyphenol structure. Its esterified derivative, Vitamin E succinate (VES), exhibits unique anticancer and healthcare functions as well as immunomodulatory effects. Natural polysaccharides are proved to be a promising material for nano-drug delivery systems, which show excellent biodegradability and biocompatibility. In this study, we employed a novel bletilla striata polysaccharide-vitamin E succinate polymer (BSP-VES) micelles to enhance the tumor targeting and anti-colon cancer effect of andrographolide (AG). Methods: BSP-VES polymer was synthesized through esterification and its structure was confirmed using 1H NMR. AG@BSP-VES was prepared via the dialysis method and the drug loading, entrapment efficiency, stability, and safety were assessed. Furthermore, the tumor targeting ability of AG@BSP-VES was evaluated through targeted cell uptake and in vivo imaging. The antitumor activity of AG@BSP-VES was measured in vitro using MTT assay, Live&Dead cell staining, and cell scratch test. Results: In this study, we successfully loaded AG into BSP-VES micelles (AG@BSP-VES), which exhibited good stability, biosafety and sustained release effect. In addition, AG@BSP-VES also showed excellent internalization capability into CT26 cells compared with NCM460 cells in vitro. Meanwhile, the specific delivery of AG@BSP-VES micelles into subcutaneous and in-situ colon tumors was observed compared with normal colon tissues in vivo during the whole experiment process (1-24 h). What's more, AG@BSP-VES micelles exhibited significant antitumor activities than BSP-VES micelles and free AG. Conclusion: The study provides a meaningful new idea and method for application in drug delivery system and targeted treatment of colon cancer based on natural polysaccharides.


Asunto(s)
Neoplasias del Colon , Diterpenos , Micelas , Polisacáridos , Animales , Neoplasias del Colon/tratamiento farmacológico , Diterpenos/química , Diterpenos/farmacología , Diterpenos/administración & dosificación , Humanos , Ratones , Línea Celular Tumoral , Polisacáridos/química , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Sistemas de Liberación de Medicamentos , Ensayos Antitumor por Modelo de Xenoinjerto , Portadores de Fármacos/química , Nanopartículas/química , Sistema de Administración de Fármacos con Nanopartículas/química , Ratones Desnudos , Ratones Endogámicos BALB C
8.
Molecules ; 29(9)2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38731484

RESUMEN

In this study, we developed a green and multifunctional bioactive nanoemulsion (BBG-NEs) of Blumea balsamifera oil using Bletilla striata polysaccharide (BSP) and glycyrrhizic acid (GA) as natural emulsifiers. The process parameters were optimized using particle size, PDI, and zeta potential as evaluation parameters. The physicochemical properties, stability, transdermal properties, and bioactivities of the BBG-NEs under optimal operating conditions were investigated. Finally, network pharmacology and molecular docking were used to elucidate the potential molecular mechanism underlying its wound-healing properties. After parameter optimization, BBG-NEs exhibited excellent stability and demonstrated favorable in vitro transdermal properties. Furthermore, it displayed enhanced antioxidant and wound-healing effects. SD rats wound-healing experiments demonstrated improved scab formation and accelerated healing in the BBG-NE treatment relative to BBO and emulsifier groups. Pharmacological network analyses showed that AKT1, CXCL8, and EGFR may be key targets of BBG-NEs in wound repair. The results of a scratch assay and Western blotting assay also demonstrated that BBG-NEs could effectively promote cell migration and inhibit inflammatory responses. These results indicate the potential of the developed BBG-NEs for antioxidant and skin wound applications, expanding the utility of natural emulsifiers. Meanwhile, this study provided a preliminary explanation of the potential mechanism of BBG-NEs to promote wound healing through network pharmacology and molecular docking, which provided a basis for the mechanistic study of green multifunctional nanoemulsions.


Asunto(s)
Antioxidantes , Emulsionantes , Emulsiones , Ácido Glicirrínico , Simulación del Acoplamiento Molecular , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Emulsiones/química , Emulsionantes/química , Emulsionantes/farmacología , Ratas , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/síntesis química , Ácido Glicirrínico/farmacología , Ácido Glicirrínico/química , Polisacáridos/química , Polisacáridos/farmacología , Tecnología Química Verde , Humanos , Ratas Sprague-Dawley , Nanopartículas/química , Aceites de Plantas/química , Aceites de Plantas/farmacología , Fabaceae/química , Masculino , Tamaño de la Partícula , Movimiento Celular/efectos de los fármacos
9.
Molecules ; 29(9)2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38731501

RESUMEN

Bacterial infection is a thorny problem, and it is of great significance to developing green and efficient biological antibacterial agents that can replace antibiotics. This study aimed to rapidly prepare a new type of green antibacterial nanoemulsion containing silver nanoparticles in one step by using Blumea balsamifera oil (BBO) as an oil phase and tea saponin (TS) as a natural emulsifier and reducing agent. The optimum preparation conditions of the AgNPs@BBO-TS NE were determined, as well as its physicochemical properties and antibacterial activity in vitro being investigated. The results showed that the average particle size of the AgNPs@BBO-TS NE was 249.47 ± 6.23 nm, the PDI was 0.239 ± 0.003, and the zeta potential was -35.82 ± 4.26 mV. The produced AgNPs@BBO-TS NE showed good stability after centrifugation and 30-day storage. Moreover, the AgNPs@BBO-TS NE had an excellent antimicrobial effect on Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. These results demonstrated that the AgNPs@BBO-TS NE produced in this study can be used as an efficient and green antibacterial agent in the biomedical field.


Asunto(s)
Antibacterianos , Emulsiones , Tecnología Química Verde , Nanopartículas del Metal , Pruebas de Sensibilidad Microbiana , Tamaño de la Partícula , Plata , Antibacterianos/farmacología , Antibacterianos/química , Plata/química , Plata/farmacología , Nanopartículas del Metal/química , Staphylococcus aureus/efectos de los fármacos , Aceites de Plantas/química , Aceites de Plantas/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Saponinas/química , Saponinas/farmacología
10.
J Pharmacol Sci ; 155(3): 101-112, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38797534

RESUMEN

Pulmonary inflammation may lead to neuroinflammation resulting in neurological dysfunction, and it is associated with a variety of acute and chronic lung diseases. Paeonol is a herbal phenolic compound with anti-inflammatory and anti-oxidative properties. The aim of this study is to understand the beneficial effects of paeonol on cognitive impairment, pulmonary inflammation and its underlying mechanisms. Pulmonary inflammation-associated cognitive deficit was observed in TNFα-stimulated mice, and paeonol mitigated the cognitive impairment by reducing the expressions of interleukin (IL)-1ß, IL-6, and NOD-like receptor family pyrin domain-containing 3 (NLRP3) in hippocampus. Moreover, elevated plasma miR-34c-5p in lung-inflamed mice was also reduced by paeonol. Pulmonary inflammation induced by intratracheal instillation of TNFα in mice resulted in immune cells infiltration in bronchoalveolar lavage fluid, pulmonary edema, and acute fibrosis, and these inflammatory responses were alleviated by paeonol orally. In MH-S alveolar macrophages, tumor necrosis factor (TNF) α- and phorbol myristate acetate (PMA)-induced inflammasome activation was ameliorated by paeonol. In addition, the expressions of antioxidants were elevated by paeonol, and reactive oxygen species production was reduced. In this study, paeonol demonstrates protective effects against cognitive deficits and pulmonary inflammation by exerting anti-inflammatory and anti-oxidative properties, suggesting a powerful benefit as a potential therapeutic agent.


Asunto(s)
Acetofenonas , Disfunción Cognitiva , Enfermedades Pulmonares , Enfermedades Pulmonares/complicaciones , Acetofenonas/farmacología , Acetofenonas/uso terapéutico , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Macrófagos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratones Endogámicos C57BL , Masculino , Animales , Ratones , Factor de Necrosis Tumoral alfa , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , MicroARNs/sangre , MicroARNs/genética , Especies Reactivas de Oxígeno/metabolismo
11.
Infect Dis Model ; 9(3): 816-827, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38725432

RESUMEN

Background: Influenza is an acute respiratory infectious disease with a significant global disease burden. Additionally, the coronavirus disease 2019 pandemic and its related non-pharmaceutical interventions (NPIs) have introduced uncertainty to the spread of influenza. However, comparative studies on the performance of innovative models and approaches used for influenza prediction are limited. Therefore, this study aimed to predict the trend of influenza-like illness (ILI) in settings with diverse climate characteristics in China based on sentinel surveillance data using three approaches and evaluate and compare their predictive performance. Methods: The generalized additive model (GAM), deep learning hybrid model based on Gate Recurrent Unit (GRU), and autoregressive moving average-generalized autoregressive conditional heteroscedasticity (ARMA-GARCH) model were established to predict the trends of ILI 1-, 2-, 3-, and 4-week-ahead in Beijing, Tianjin, Shanxi, Hubei, Chongqing, Guangdong, Hainan, and the Hong Kong Special Administrative Region in China, based on sentinel surveillance data from 2011 to 2019. Three relevant metrics, namely, Mean Absolute Percentage Error (MAPE), Root Mean Squared Error (RMSE), and R squared, were calculated to evaluate and compare the goodness of fit and robustness of the three models. Results: Considering the MAPE, RMSE, and R squared values, the ARMA-GARCH model performed best, while the GRU-based deep learning hybrid model exhibited moderate performance and GAM made predictions with the least accuracy in the eight settings in China. Additionally, the models' predictive performance declined as the weeks ahead increased. Furthermore, blocked cross-validation indicated that all models were robust to changes in data and had low risks of overfitting. Conclusions: Our study suggested that the ARMA-GARCH model exhibited the best accuracy in predicting ILI trends in China compared to the GAM and GRU-based deep learning hybrid model. Therefore, in the future, the ARMA-GARCH model may be used to predict ILI trends in public health practice across diverse climatic zones, thereby contributing to influenza control and prevention efforts.

12.
J Formos Med Assoc ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38777672

RESUMEN

Kidney transplant recipients have an increased risk of cytomegalovirus (CMV) infection and disease. A strategy for mitigating the risk of CMV infection in kidney transplant recipients has not yet been established in Taiwan. The Transplantation Society of Taiwan aimed to develop a consensus by expert opinion on the prevention and management of CMV infection. Based on the results of Consensus Conference, we suggested low-dose valganciclovir prophylaxis (450 mg once daily) for kidney transplant recipients. The prophylaxis duration was ≥6 months for high-risk (D+/R-) patients and 3 months for moderate-risk (R+) patients. Even for low-risk (D-/R-) patients, prophylaxis for at least 3 months is recommended because of the high seroprevalence of CMV in Taiwan. CMV prophylaxis was suggested after anti-thymocyte globulin treatment but not after methylprednisolone pulse therapy. Routine surveillance after prophylaxis, secondary prophylaxis after CMV disease treatment, and mTOR inhibitors for primary CMV prophylaxis were not recommended. Letermovir and marabavir are emerging CMV agents used for prophylaxis and refractory CMV disease. CMV immunoglobulins have been used to treat refractory CMV disease in Taiwan. We hope this consensus will help professionals manage patients with CMV in Taiwan to improve the quality of care.

13.
Int J Biol Macromol ; 270(Pt 1): 132035, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38705316

RESUMEN

The frequently encountered wastewater contaminations, including soluble aromatic compound and dye pollutants, pathogenic bacteria, and insoluble oils, have resulted in significant environmental and human health issues. It poses a challenge to utilize identical materials for the treatment of complex wastewater. Herein, in this research, multifunctional Ag NPs/guar gum hybrid hydrogels were fabricated using a facile in situ reduction and self-crosslinking method for efficient remediation of complex wastewater. The Ag NPs/guar gum hybrid hydrogel showed remarkable remodeling, adhesive, and self-healing characteristics, which was favorable for its versatile applications. The combination of Ag NPs with the guar gum skeleton endowed the hybrid hydrogel with exceptional catalytic activity for reducing aromatic compounds and dye pollutants, as well as remarkable antibacterial efficacy against pathogenic bacteria. In addition, the Ag NPs/guar gum hybrid hydrogel could be employed to coat a variety of substrates, including cotton fabrics and stainless steel meshes. The hydrogel coated cotton fabrics and meshes presented superhydrophilicity/underwater superoleophobicity, excellent antifouling capacity, and outstanding recyclability, which could be successfully applied for efficient separation of oil-water mixtures. The findings of this work provide a feasible and cost-effective approach for the remediation of intricate wastewater.


Asunto(s)
Antibacterianos , Galactanos , Hidrogeles , Mananos , Nanopartículas del Metal , Gomas de Plantas , Plata , Galactanos/química , Gomas de Plantas/química , Plata/química , Mananos/química , Antibacterianos/química , Antibacterianos/farmacología , Catálisis , Nanopartículas del Metal/química , Hidrogeles/química , Aguas Residuales/química , Purificación del Agua/métodos , Agua/química , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/aislamiento & purificación , Aceites/química
14.
J Transl Med ; 22(1): 302, 2024 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-38521921

RESUMEN

BACKGROUND: Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by fluctuating muscle weakness. Despite the availability of established therapies, the management of MG symptoms remains suboptimal, partially attributed to lack of efficacy or intolerable side-effects. Therefore, new effective drugs are warranted for treatment of MG. METHODS: By employing an analytical framework that combines Mendelian randomization (MR) and colocalization analysis, we estimate the causal effects of blood druggable expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs) on the susceptibility of MG. We subsequently investigated whether potential genetic effects exhibit cell-type specificity by utilizing genetic colocalization analysis to assess the interplay between immune-cell-specific eQTLs and MG risk. RESULTS: We identified significant MR results for four genes (CDC42BPB, CD226, PRSS36, and TNFSF12) using cis-eQTL genetic instruments and three proteins (CTSH, PRSS8, and CPN2) using cis-pQTL genetic instruments. Six of these loci demonstrated evidence of colocalization with MG susceptibility (posterior probability > 0.80). We next undertook genetic colocalization to investigate cell-type-specific effects at these loci. Notably, we identified robust evidence of colocalization, with a posterior probability of 0.854, linking CTSH expression in TH2 cells and MG risk. CONCLUSIONS: This study provides crucial insights into the genetic and molecular factors associated with MG susceptibility, singling out CTSH as a potential candidate for in-depth investigation and clinical consideration. It additionally sheds light on the immune-cell regulatory mechanisms related to the disease. However, further research is imperative to validate these targets and evaluate their feasibility for drug development.


Asunto(s)
Predisposición Genética a la Enfermedad , Miastenia Gravis , Humanos , Multiómica , Estudio de Asociación del Genoma Completo , Miastenia Gravis/genética , Sitios de Carácter Cuantitativo/genética , Polimorfismo de Nucleótido Simple/genética
15.
J Med Virol ; 96(3): e29515, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38469923

RESUMEN

Hepatitis B virus (HBV) infection significantly impacts Asian populations. The influences of continuous HBV antigen and inflammatory stimulation to T cells in chronic hepatitis B (CHB) remain unclear. In this study, we first conducted bioinformatics analysis to assess T-cell signaling pathways in CHB patients. In a Taiwanese cohort, we examined the phenotypic features of HBVcore -specific T cells and their correlation with clinical parameters. We used core protein overlapping peptides from the Taiwan prevalent genotype B HBV to investigate the antiviral response and the functional implication of HBV-specific T cells. In line with Taiwanese dominant HLA-alleles, we also evaluated ex vivo HBVcore -specific T cells by pMHC-tetramers targeting epitopes within HBV core protein. Compared to healthy subjects, we disclosed CD8 T cells from CHB patients had higher activation marker CD38 levels but showed an upregulation in the inhibitory receptor PD-1. Our parallel study showed HBV-specific CD8 T cells were more activated with greater PD-1 expression than CMV-specific subset and bulk CD8 T cells. Moreover, our longitudinal study demonstrated a correlation between the PD-1 fluctuation pattern of HBVcore -specific CD8 T cells and liver inflammation in CHB patients. Our research reveals the HBV core antigen-mediated immunopathologic profile of CD8 T cells in chronic HBV infection. Our findings suggest the PD-1 levels of HBVcore -specific CD8 T cells can be used as a valuable indicator of personal immune response for clinical application in hepatitis management.


Asunto(s)
Hepatitis B Crónica , Hepatitis B , Humanos , Virus de la Hepatitis B/genética , Receptor de Muerte Celular Programada 1/genética , Estudios Longitudinales , Antígenos del Núcleo de la Hepatitis B , Linfocitos T CD8-positivos
16.
Mol Pharm ; 21(5): 2298-2314, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38527915

RESUMEN

Hypertrophic scars (HS) still remain an urgent challenge in the medical community. Traditional Chinese medicine (TCM) has unique advantages in the treatment of HS. However, due to the natural barrier of the skin, it is difficult for the natural active components of TCM to more effectively penetrate the skin and exert therapeutic effects. Therefore, the development of an efficient drug delivery system to facilitate enhanced transdermal absorption of TCM becomes imperative for its clinical application. In this study, we designed a compound Salvia miltiorrhiza-Blumea balsamifera nanoemulsion gel (CSB-NEG) and investigated its therapeutic effects on rabbit HS models. The prescription of CSB-NEG was optimized by single-factor, pseudoternary phase diagram, and central composite design experiments. The results showed that the average particle size and PDI of the optimized CSB-NE were 46.0 ± 0.2 nm and 0.222 ± 0.004, respectively, and the encapsulation efficiency of total phenolic acid was 93.37 ± 2.56%. CSB-NEG demonstrated excellent stability and skin permeation in vitro and displayed a significantly enhanced ability to inhibit scar formation compared to the CSB physical mixture in vivo. After 3 weeks of CSB-NEG treatment, the scar appeared to be flat, pink, and flexible. Furthermore, this treatment also resulted in a decrease in the levels of the collagen I/III ratio and TGF-ß1 and Smad2 proteins while simultaneously promoting the growth and remodeling of microvessels. These findings suggest that CSB-NEG has the potential to effectively address the barrier properties of the skin and provide therapeutic benefits for HS, offering a new perspective for the prevention and treatment of HS.


Asunto(s)
Cicatriz Hipertrófica , Emulsiones , Geles , Salvia miltiorrhiza , Absorción Cutánea , Conejos , Animales , Cicatriz Hipertrófica/tratamiento farmacológico , Salvia miltiorrhiza/química , Absorción Cutánea/efectos de los fármacos , Emulsiones/química , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Modelos Animales de Enfermedad , Piel/efectos de los fármacos , Piel/patología , Piel/metabolismo , Administración Cutánea , Tamaño de la Partícula , Masculino , Nanopartículas/química , Medicina Tradicional China/métodos , Oído/patología , Sistemas de Liberación de Medicamentos/métodos
17.
Cell Death Discov ; 10(1): 154, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38538582

RESUMEN

We have previously shown that nucleosome assembly protein 1-like 1 (NAP1L1) plays an important role in the abnormal proliferation of hepatocellular carcinoma (HCC) cells. However, the effects of NAP1L1 on the malignant behaviour of HCC cells, including cell migration, invasion and apoptosis, remain unclear. Baculoviral IAP repeat-containing 2 (BIRC2) plays a key role in initiating the abnormal proliferation, apoptotic escape and multidrug resistance of HCC cells; however, the mechanisms through which its stability is regulated in HCC remain elusive. Here, we found that knockdown of NAP1L1 inhibited the proliferation of HCC cells and activated apoptotic pathways but did not remarkably affect the migratory and invasive abilities of HCC cells. In addition, knockdown of NAP1L1 did not alter the expression of BIRC2 at the transcriptional level but substantially reduced its expression at the translational level, suggesting that NAP1L1 is involved in the post-translational modification (such as ubiquitination) of BIRC2. Furthermore, BIRC2 was highly expressed in human HCC tissues and promoted the proliferation and apoptotic escape of HCC cells. Co-immunoprecipitation (Co-IP) assay and mass spectrometry revealed that NAP1L1 and BIRC2 did not bind to each other; however, ubiquitin protein ligase E3 component n-recognin 4 (UBR4) was identified as an intermediate molecule associating NAP1L1 with BIRC2. Knockdown of NAP1L1 promoted the ubiquitin-mediated degradation of BIRC2 through the ubiquitin-protein junction of UBR4, which in turn inhibited the proliferation and apoptotic escape of HCC cells and exerted anti-tumour effects. In conclusion, this study reveals a novel mechanism through which NAP1L1 regulates the ubiquitination of BIRC2 through UBR4, thereby determining the progression of HCC. Based on this mechanism, suppression of NAP1L1 may inhibit tumour progression in patients with HCC with high protein expression of NAP1L1 or BIRC2.

18.
Inorg Chem ; 63(14): 6276-6284, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38546717

RESUMEN

Molecules with high point-group symmetry are interesting prototype species in the textbook. As transition metal-centered boron clusters tend to have highly symmetric structures to fulfill multicenter bonding and high stability, new boron clusters with rare point-group symmetry may be viable. Through in-depth scrutiny over the structures of experimentally already observed transition metal-centered boron-wheel complexes, geometric and electronic design principles are summarized, based on which we studied M©B11k- (M = Y, La; Zr, Hf; k = 1, 2) clusters and found that a Y©B112- boron-wheel complex has an unprecedented D11h point-group symmetry. The remarkable stability of the planar Y©B112- complex is illustrated via extensive global-minimum structural search as well as comprehensive chemical bonding analyses. Similar to other boron-wheel complexes, the Y©B112- complex is shown to possess σ and π double aromaticity, indeed following the electronic design principle previously summarized. This new compound is expected to be experimentally identified, which will extend the currently known largest possible planar molecular symmetry and enrich the metal-centered boron-wheel class.

19.
Adv Sci (Weinh) ; 11(15): e2308958, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38342625

RESUMEN

Direct ethanol fuel cells (DEFCs) play an indispensable role in the cyclic utilization of carbon resources due to its high volumetric energy density, high efficiency, and environmental benign character. However, owing to the chemically stable carbon-carbon (C─C) bond of ethanol, its incomplete electrooxidation at the anode severely inhibits the energy and power density output of DEFCs. The efficiency of C─C bond cleaving on the state-of-the-art Pt or Pd catalysts is reported as low as 7.5%. Recently, tremendous efforts are devoted to this field, and some effective strategies are put forward to facilitate the cleavage of the C─C bond. It is the right time to summarize the major breakthroughs in ethanol electrooxidation reaction. In this review, some optimization strategies including constructing core-shell nanostructure with alloying effect, doping other metal atoms in Pt and Pd catalysts, engineering composite catalyst with interface synergism, introducing cascade catalytic sites, and so on, are systematically summarized. In addition, the catalytic mechanism as well as the correlations between the catalyst structure and catalytic efficiency are further discussed. Finally, the prevailing limitations and feasible improvement directions for ethanol electrooxidation are proposed.

20.
Virus Res ; 343: 199343, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38423214

RESUMEN

African swine fever (ASF), caused by the ASF virus (ASFV), is a hemorrhagic and fatal viral disease that affects Eurasian wild boars and domestic pigs, posing a substantial threat to the global pig breeding industry. ASFV, a double-stranded DNA virus, possesses a large genome containing up to 160 open reading frames, most of which exhibit unknown functions. The B125R gene of ASFV, located at the 105595-105972 bp site in the ASFV-SY18 genome, remains unexplored. In this study, we discovered that B125R deletion did not affect recombinant virus rescue, nor did it hinder viral replication during the intermediate growth phase. Although the virulence of the recombinant strain harboring this deletion was attenuated, intramuscular inoculation of the recombinant virus in pigs at doses of 102 or 104 TCID50 resulted in mortality. Moreover, sequencing analysis of six recombinant strains obtained from three independent experiments consistently revealed an adenine insertion at the 47367-47375 bp site in the A104R gene due to the B125R deletion, leading to premature termination of this gene. Intriguingly, this insertion did not influence the transcription of the A104R gene between the recombinant and parental strains. Consequently, we postulate that the deletion of the B125R gene in ASFV-SY18 or other genotype II strains may marginally attenuate virulence in domestic pigs.


Asunto(s)
Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Porcinos , Animales , Virus de la Fiebre Porcina Africana/genética , Sus scrofa , Virulencia , Mutación del Sistema de Lectura , Eliminación de Gen
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