Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 192
Filtrar
1.
J Stomatol Oral Maxillofac Surg ; : 102028, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39226985

RESUMEN

Branchial cleft cysts are common congenital lateral neck masses, with 95 % originating from the second branchial cleft. Although most cysts are benign, there are rare instances of malignancy. Here, we present a rare case of primary branchiogenic carcinoma originating from both sides of the neck in a 68-year-old male. Through a detailed analysis of this rare bilateral primary branchiogenic carcinoma, we present the complexity of diagnosing such rare phenomena and the limitations of existing diagnostic methods, emphasizing the need to improve diagnostic methods and the importance of further research for understanding and dealing with similar cases.

2.
Chem Commun (Camb) ; 60(67): 8892-8895, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39086281

RESUMEN

A biological nanoplatform (Gal-ANI@ZnAP NPs) was constructed based on a prodrug-skeletal metal-organic framework (MOF) using purine nucleobase analogue prodrug 6-allylthiopurine as a bioactive ligand, and functionalized with AIE fluorescent PARP inhibitor glycoconjugate for visualization therapy and synthetic lethal cancer therapy. This nanoplatform could actively target cancer cells, selectively release drugs in response to esterase/pH, and visualize drug uptake. In vitro studies revealed that Gal-ANI@ZnAP NPs increased the synthetic lethality in cancer cells by inducing DNA repair failure with the simultaneous targeting of PARP and nucleotide metabolism, thereby exhibiting a significant cancer-killing effect. The study presents a novel strategy to construct an AIE nanoplatform using pharmaceutical molecules for drug uptake visualization and boosting synthetic lethality in cancer.


Asunto(s)
Antineoplásicos , Estructuras Metalorgánicas , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Humanos , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/química , Inhibidores de Poli(ADP-Ribosa) Polimerasas/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Glicosilación , Profármacos/química , Profármacos/farmacología , Profármacos/síntesis química , Línea Celular Tumoral , Nanopartículas/química , Ensayos de Selección de Medicamentos Antitumorales , Supervivencia Celular/efectos de los fármacos
5.
World J Gastrointest Oncol ; 16(7): 2952-2959, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39072152

RESUMEN

BACKGROUND: Radical laparoscopic gastrectomy is an important treatment modality for gastric cancer. Surgery requires general anesthesia, and patients are susceptible to the effects of anesthetic drugs and carbon dioxide insufflation during the procedure, leading to inflammation or severe pain, which can affect patient outcome. AIM: To explore the efficacy of combining dexmedetomidine (DEX) with nalbuphine in patients underwent laparoscopic radical gastrectomy for gastric cancer. METHODS: Patients scheduled to undergo laparoscopic radical gastrectomy were selected and randomly assigned to A or B group. In A group, patients received an intravenous injection of nalbuphine 0.2 mg/kg + DEX 0.4 µg/kg 10 min before the end of surgery; in B group, patients received only an intravenous injection of nalbuphine. The trends in hemodynamic parameter fluctuations, awakening quality during the recovery period, serum inflammatory markers, agitation scores, cough severity, incidence, and duration of postoperative delirium (POD) were compared. RESULTS: The mean arterial pressure and heart rate in the A group were more stable (P < 0.05). The A group had a lower average awakening time, extubation time, and agitation scores during recovery than the B group. Agitation control in the A group was more effective at different time points (P < 0.05). Patients in the A group had lower serum interleukin (IL)-6, tumour necrosis factor alpha, and IL-10 levels at 1 h after surgery than the B group. The incidence of coughing and duration of POD were lower and shorter in the A group than in the B group. Adverse reactions caused by the two anesthesia methods were less frequent in the A group than in the B group (P < 0.05). CONCLUSION: The use of DEX and nalbuphine in patients undergoing laparoscopic radical gastrectomy for gastric cancer help reducing the inflammatory response, cough severity, and agitation and helps maintain hemodynamic stability.

6.
Polymers (Basel) ; 16(12)2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38932025

RESUMEN

The direct copolymerization of ethylene with polar monomers to produce functional polyolefins continues to be highly appealing due to its simple operation process and controllable product microstructure. Low-cost nickel catalysts have been extensively utilized in academia for the synthesis of polar polyethylenes. However, the development of high-temperature copolymerization catalysts suitable for industrial production conditions remains a significant challenge. Classified by the resultant copolymers, this review provides a comprehensive summary of the research progress in nickel complex catalyzed ethylene-polar monomer copolymerization at elevated temperatures in the past five years. The polymerization results of ethylene-methyl acrylate copolymers, ethylene-tert-butyl acrylate copolymers, ethylene-other fundamental polar monomer copolymers, and ethylene-special polar monomer copolymers are thoroughly summarized. The involved nickel catalysts include the phosphine-phenolate type, bisphosphine-monoxide type, phosphine-carbonyl type, phosphine-benzenamine type, and the phosphine-enolate type. The effective modulation of catalytic activity, molecular weight, molecular weight distribution, melting point, and polar monomer incorporation ratio by these catalysts is concluded and discussed. It reveals that the optimization of the catalyst system is mainly achieved through the methods of catalyst structure rational design, extra additive introduction, and single-site catalyst heterogenization. As a result, some outstanding catalysts are capable of producing polar polyethylenes that closely resemble commercial products. To achieve industrialization, it is essential to further emphasize the fundamental science of high-temperature copolymerization systems and the application performance of resultant polar polyethylenes.

7.
mBio ; 15(7): e0122024, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38842315

RESUMEN

Hybrid two-component systems (HTCSs) comprise a major class of transcription regulators of polysaccharide utilization genes in Bacteroides. Distinct from classical two-component systems in which signal transduction is carried out by intermolecular phosphotransfer between a histidine kinase (HK) and a cognate response regulator (RR), HTCSs contain the membrane sensor HK and the RR transcriptional regulator within a single polypeptide chain. Tethering the DNA-binding domain (DBD) of the RR with the dimeric HK domain in an HTCS could potentially promote dimerization of the DBDs and would thus require a mechanism to suppress DNA-binding activity in the absence of stimulus. Analysis of phosphorylation and DNA-binding activities of several HTCSs from Bacteroides thetaiotaomicron revealed a DBD suppression mechanism in which an inhibitory interaction between the DBD and the phosphoryl group-accepting receiver domain (REC) decreases autophosphorylation rates of HTCS-RECs and represses DNA-binding activities in the absence of phosphorylation. Sequence analyses and structure predictions identified a highly conserved sequence motif correlated with a conserved inhibitory domain arrangement of REC and DBD. The presence of the motif, as in most HTCSs, or its absence, in a small subset of HTCSs, is likely predictive of two distinct regulatory mechanisms evolved for different glycans. Substitutions within the conserved motif relieve the inhibitory interaction and result in elevated DNA-binding activities in the absence of phosphorylation. Our data suggest a fundamental regulatory mechanism shared by most HTCSs to suppress DBD activities using a conserved inhibitory interdomain arrangement to overcome the challenge of the fused HK and RR components. IMPORTANCE: Different dietary and host-derived complex carbohydrates shape the gut microbial community and impact human health. In Bacteroides, the prevalent gut bacteria genus, utilization of these diverse carbohydrates relies on different gene clusters that are under sophisticated control by various signaling systems, including the hybrid two-component systems (HTCSs). We have uncovered a highly conserved regulatory mechanism in which the output DNA-binding activity of HTCSs is suppressed by interdomain interactions in the absence of stimulating phosphorylation. A consensus amino acid motif is found to correlate with the inhibitory interaction surface while deviations from the consensus can lead to constitutive activation. Understanding of such conserved HTCS features will be important to make regulatory predictions for individual systems as well as to engineer novel systems with substitutions in the consensus to explore the glycan regulation landscape in Bacteroides.


Asunto(s)
Proteínas Bacterianas , Regulación Bacteriana de la Expresión Génica , Fosforilación , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/química , Unión Proteica , Bacteroides thetaiotaomicron/genética , Bacteroides thetaiotaomicron/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Bacteroides/genética , Bacteroides/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , ADN Bacteriano/genética , ADN Bacteriano/metabolismo , Histidina Quinasa/metabolismo , Histidina Quinasa/genética , Histidina Quinasa/química , Dominios Proteicos , Transducción de Señal
8.
Tob Induc Dis ; 222024.
Artículo en Inglés | MEDLINE | ID: mdl-38895165

RESUMEN

INTRODUCTION: The rapid growth of e-cigarette usage among youth and young people has emerged as a significant public health concern. It is imperative to initiate effective vaping prevention campaigns and undertake relevant research to address this pressing issue. This research seeks to identify effective video advertisements to deter young people from starting to use e-cigarettes. It aims to offer evidence-based insights and recommendations for creating communication materials and designing messages for youth e-cigarette prevention efforts. METHODS: College students aged 18-24 years (n=40) participated in focus groups within this qualitative study. After viewing four stimulus videos, participants discussed what they perceived as effective and ineffective video characteristics, as well as suggestions for future videos. RESULTS: Effective video characteristics included the use of real-life testimonials, displaying specific health hazards, revealing harmful chemical ingredients and the deceptive nature of flavors, and positively perceived effectiveness. Participants generally found that videos with strong visual impact and graphics were more engaging and that approaches using fear and emotion were more effective. Ineffective characteristics included complex and exaggerated information, lack of empathy and irrelevance, insufficiently specific information, extreme and death-themed content, industry messages, as well as preachy tones, animations, metaphors, dull formats, excessive length, and scenes of e-cigarette use. CONCLUSIONS: Developing anti-e-cigarette campaign materials for youth necessitates target audience-focused qualitative research. This helps in deeply exploring and identifying effective themes and messages, as well as video characteristics and details while avoiding ineffective or even misleading messages and themes from young people's perspectives outside the United States. Future development of e-cigarette prevention videos for Chinese college students may consider incorporating localized real-life testimonial cases to convey specific harms, including self-efficacy information, and utilizing fear and emotional appeals.

9.
Clin Exp Med ; 24(1): 99, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38748269

RESUMEN

Current clinical guidelines limit surgical intervention to patients with cT1-2N0M0 small cell lung cancer (SCLC). Our objective was to reassess the role of surgery in SCLC management, and explore novel prognostic indicators for surgically resected SCLC. We reviewed all patients diagnosed with SCLC from January 2011 to April 2021 in our institution. Survival analysis was conducted using the Kaplan-Meier method, and independent prognostic factors were assessed through the Cox proportional hazard model. In addition, immunohistochemistry (IHC) staining was performed to evaluate the predictive value of selected indicators in the prognosis of surgically resected SCLC patients. In the study, 177 SCLC patients undergoing surgical resection were ultimately included. Both univariate and multivariate Cox analysis revealed that incomplete postoperative adjuvant therapy emerged as an independent risk factor for adverse prognosis (p < 0.001, HR 2.96). Survival analysis revealed significantly superior survival among pN0-1 patients compared to pN2 patients (p < 0.0001). No significant difference in postoperative survival was observed between pN1 and pN0 patients (p = 0.062). Patients with postoperative stable disease (SD) exhibited lower levels of tumor inflammatory cells (TIC) (p = 0.0047) and IFN-γ expression in both area and intensity (p < 0.0001 and 0.0091, respectively) compared to those with postoperative progressive disease (PD). Conversely, patients with postoperative SD showed elevated levels of stromal inflammatory cells (SIC) (p = 0.0453) and increased counts of CD3+ and CD8+ cells (p = 0.0262 and 0.0330, respectively). Survival analysis indicated that high levels of SIC, along with low levels of IFN-γ+ cell area within tumor tissue, may correlate positively with improved prognosis in surgically resected SCLC (p = 0.017 and 0.012, respectively). In conclusion, the present study revealed that the patients with pT1-2N1M0 staging were a potential subgroup of SCLC patients who may benefit from surgery. Complete postoperative adjuvant therapy remains an independent factor promoting a better prognosis for SCLC patients undergoing surgical resection. Moreover, CD3, CD8, IFN-γ, TIC, and SIC may serve as potential indicators for predicting the prognosis of surgically resected SCLC.


Asunto(s)
Complejo CD3 , Inmunohistoquímica , Interferón gamma , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Pronóstico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/mortalidad , Interferón gamma/metabolismo , Anciano , Carcinoma Pulmonar de Células Pequeñas/cirugía , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Complejo CD3/metabolismo , Antígenos CD8/metabolismo , Antígenos CD8/análisis , Adulto , Biomarcadores de Tumor/análisis , Análisis de Supervivencia , Anciano de 80 o más Años , Estimación de Kaplan-Meier , Células del Estroma/patología , Células del Estroma/metabolismo
10.
Nutrients ; 16(9)2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38732567

RESUMEN

Imbalances in lipid uptake and efflux and inflammation are major contributors to foam cell formation, which is considered a therapeutic target to protect against atherosclerosis. Naringin, a citrus flavonoid abundant in citrus fruits, has been reported to exert an antiatherogenic function, but its pharmacological mechanism is unclear. Naringin treatment effectively inhibits foam cell formation in THP-1 and RAW264.7 macrophages. In this study, mechanically, naringin maintained lipid homeostasis within macrophages through downregulation of the key genes for lipid uptake (MSR1 and CD36) and the upregulation of ABCA1, ABCG1 and SR-B1, which are responsible for cholesterol efflux. Meanwhile, naringin significantly decreased the cholesterol synthesis-related genes and increased the genes involved in cholesterol metabolism. Subsequently, the results showed that ox-LDL-induced macrophage inflammatory responses were inhibited by naringin by reducing the proinflammatory cytokines IL-1ß, IL-6 and TNF-α, and increasing the anti- inflammatory cytokine IL-10, which was further verified by the downregulation of pro-inflammatory and chemokine-related genes. Additionally, we found that naringin reprogrammed the metabolic phenotypes of macrophages by suppressing glycolysis and promoting lipid oxidation metabolism to restore macrophage phenotypes and functions. These results suggest that naringin is a potential drug for the treatment of AS as it inhibits macrophage foam cell formation by regulating metabolic phenotypes and inflammation.


Asunto(s)
Flavanonas , Células Espumosas , Homeostasis , Metabolismo de los Lípidos , Animales , Humanos , Ratones , Colesterol/metabolismo , Citocinas/metabolismo , Flavanonas/farmacología , Células Espumosas/efectos de los fármacos , Células Espumosas/metabolismo , Homeostasis/efectos de los fármacos , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Metabolismo de los Lípidos/efectos de los fármacos , Lipoproteínas LDL/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Fenotipo , Células RAW 264.7 , Células THP-1
11.
Immunotherapy ; 16(7): 465-480, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38511241

RESUMEN

Aim: This study aims to clarify the efficacy and adverse effects of immune checkpoint inhibitors (ICIs) in the lung cancer patients with a history of interstitial lung disease (ILD). Methods: From the inception of the database to 4 April 2023, we systematically searched the four databases. Results: The objective remission rate, disease control rate, incidence of immune-associated pneumonitis (ICIP) in the combined ILD group were significantly higher than those in the non-combined ILD group. There were no significant differences between the two groups in progression-free survival, overall survival, renal insufficiency, thyroid dysfunction and gastrointestinal toxicity. Conclusion: Generally, a pre-existing ILD history can increase the efficacy and incidence of ICIs' adverse reactions. Therefore, ICIs should be administered with caution.


Immune checkpoint inhibitors are a type of immunotherapy used to treat lung cancer. Some experts disagree over whether it is safe and effective to use this type of immunotherapy in people with lung cancer who also have lung disease. In this paper, the researchers analyzed the results of lots of different studies relating to the use of immune checkpoint inhibitors to treat lung cancer in patients with and without lung disease. They wanted to find out whether immune checkpoint inhibitors differed in their effectiveness between the two groups of patients. They also looked at whether patients with lung disease experienced more negative side effects from the immunotherapy treatment. The researchers found that patients with lung disease had a bigger response to immune checkpoint inhibitor treatment than patients without lung disease. This means that this type of immunotherapy is likely to be effective at treating lung cancer in patients with lung disease. However, the researchers also found that this patient group was more likely to experience negative side effects from the immunotherapy treatment. In particular, there were many more cases of pneumonia in this group than in the patients without lung disease. Therefore, doctors should be cautious when using immunotherapy to treat lung cancer patients with lung disease, ensuring they take measures to prevent pneumonia and be better prepared in case negative side effects occur.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Enfermedades Pulmonares Intersticiales , Neoplasias Pulmonares , Humanos , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/etiología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/complicaciones
12.
Angew Chem Int Ed Engl ; 63(22): e202404258, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38454791

RESUMEN

Engineering advantageous defects to construct well-defined active sites in catalysts is promising but challenging to achieve efficient photocatalytic NH3 synthesis from N2 and H2O due to the chemical inertness of N2 molecule. Here, we report defective Fe-based metal-organic framework (MOF) photocatalysts via a non-thermal plasma-assisted synthesis strategy, where their NH3 production capability is synergistically regulated by two types of defects, namely, bridging organic ligands and terminal inorganic ligands (OH- and H2O). Specially, the optimized MIL-100(Fe) catalysts, where there are only terminal inorganic ligand defects and coexistence of dual defects, exhibit the respective 1.7- and 7.7-fold activity enhancement comparable to the pristine catalyst under visible light irradiation. As revealed by experimental and theoretical calculation results, the dual defects in the catalyst induce the formation of abundant and highly accessible coordinatively unsaturated Fe active sites and synergistically optimize their geometric and electronic structures, which favors the injection of more d-orbital electrons in Fe sites into the N2 π* antibonding orbital to achieve N2 activation and the formation of a key intermediate *NNH in the reaction. This work provides a guidance on the rational design and accurate construction of porous catalysts with precise defective structures for high-performance activation of catalytic molecules.

13.
Neuroscience ; 545: 111-124, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38492796

RESUMEN

Armcx1 is a member of the ARMadillo repeat-Containing protein on the X chromosome (ARMCX) family, which is recognized to have evolutionary conserved roles in regulating mitochondrial transport and dynamics. Previous research has shown that Armcx1 is expressed at higher levels in mice after axotomy and in adult retinal ganglion cells after crush injury, and this protein increases neuronal survival and axonal regeneration. However, its role in traumatic brain injury (TBI) is unclear. Therefore, the aim of this study was to assess the expression of Armcx1 after TBI and to explore possible related mechanisms by which Armcx1 is involved in TBI. We used C57BL/6 male mice to model TBI and evaluated the role of Armcx1 in TBI by transfecting mice with Armcx1 small interfering RNA (siRNA) to inhibit Armcx1 expression 24 h before TBI modeling. Western blotting, immunofluorescence, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, Nissl staining, transmission electron microscopy, adenosine triphosphate (ATP) level measurement, neuronal apoptosis analysis, neurological function scoring and the Morris water maze were performed. The results demonstrated that Armcx1 protein expression was elevated after TBI and that the Armcx1 protein was localized in neurons and astroglial cells in cortical tissue surrounding the injury site. In addition, inhibition of Armcx1 expression further led to impaired mitochondrial transport, abnormal morphology, reduced ATP levels, aggravation of neuronal apoptosis and neurological dysfunction, and decrease Miro1 expression. In conclusion, our findings indicate that Armcx1 may exert neuroprotective effects by ameliorating neurological injury after TBI through a mitochondrial transport pathway involving Miro1.


Asunto(s)
Proteínas del Dominio Armadillo , Lesiones Traumáticas del Encéfalo , Ratones Endogámicos C57BL , Mitocondrias , Proteínas de Unión al GTP rho , Animales , Masculino , Ratones , Adenosina Trifosfato/metabolismo , Apoptosis/fisiología , Proteínas del Dominio Armadillo/metabolismo , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/patología , Modelos Animales de Enfermedad , Aprendizaje por Laberinto/fisiología , Mitocondrias/metabolismo , Neuronas/metabolismo , Neuronas/patología , Proteínas de Unión al GTP rho/metabolismo
14.
Polymers (Basel) ; 16(6)2024 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-38543368

RESUMEN

Since the discovery of α-diimine catalysts in 1995, an extensive series of Brookhart-type complexes have shown their excellence in catalyzing ethylene polymerizations with remarkable activity and a high molecular weight. However, although this class of palladium complexes has proven proficiency in catalyzing ethylene copolymerization with various polar monomers, the α-diimine nickel catalysts have generally exhibited a much worse performance in these copolymerizations compared to their palladium counterparts. Recently, Brookhart et al. reported a notable exception, demonstrating that α-diimine nickel catalysts could catalyze the ethylene copolymerization with some vinylalkoxysilanes effectively, producing functionalized polyethylene incorporating trialkoxysilane (-Si(OR)3) groups. This breakthrough is significant since Pd-catalyzed copolymerizations are commercially less usable due to the high cost of palladium. Thus, the utilization of Ni, given its abundance in raw materials and cost-effectiveness, is a landmark in ethylene/polar vinyl monomer copolymerization. Inspired by these findings, we used density functional theory (DFT) calculations to investigate the mechanistic study of ethylene copolymerization with vinyltrimethoxysilane (VTMoS) catalyzed by Brookhart-type nickel catalysts, aiming to elucidate the molecular-level understanding of this unique reaction. Initially, the nickel complexes and cationic active species were optimized through DFT calculations. Subsequently, we explored the mechanisms including the chain initiation, chain propagation, and chain termination of ethylene homopolymerization and copolymerization catalyzed by Brookhart-type complexes. Finally, we conducted an energetic analysis of both the in-chain and chain-end of silane enchainment. It was found that chain initiation is the dominant step in the ethylene homopolymerization catalyzed by the α-diimine Ni complex. The 1,2- and 2,1-insertion of vinylalkoxysilane exhibit similar barriers, explaining the fact that both five-membered and four-membered chelates were identified experimentally. After the VTMoS insertion, the barriers of ethylene reinsertion become higher, indicating that this step is the rate-determining step, which could be attributed to the steric hindrance between the incoming ethylene and the bulky silane substrate. We have also reported the energetic analysis of the distribution of polar substrates. The dominant pathway of chain-end -Si(OR)3 incorporation is suggested as chain-walking → ring-opening → ethylene insertion, and the preference of chain-end -Si(OR)3 incorporation is primarily attributed to the steric repulsion between the pre-inserted silane group and the incoming ethylene molecule, reducing the likelihood of in-chain incorporation.

15.
Brain Res Bull ; 207: 110870, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38185389

RESUMEN

Traumatic brain injury (TBI) is a common disease worldwide with high mortality and disability rates. Besides the primary mechanical injury, the secondary injury associated with TBI can also induce numerous pathological changes, such as brain edema, nerve apoptosis, and neuroinflammation, which further aggravates neurological dysfunction and even causes the death due to the primary injury. Among them, neuronal apoptosis is a key link in the injury. Melanocortin-1 receptor (MC1R) is a G protein coupled receptor, belonging to the melanocortin receptor family. Studies have shown that activation of MC1R inhibits oxidative stress and apoptosis, and confers neuroprotective effects against various neurological diseases. Merlin is a protein product of the NF2 gene, which is widely expressed in the central nervous system (CNS) of mice, rats, and humans. Studies have indicated that Merlin is associated with MC1R. In this study, we explored the anti-apoptotic effects and potential mechanisms of MC1R. A rat model of TBI was established through controlled cortical impact. The MC1R-specific agonist Nle4-D-Phe7-α-Melanocyte (NDP-MSH) and the inhibitor MSG-606 were employed to explore the effects of MC1R and Merlin following TBI and investigated the associated mechanisms. The results showed that the expression levels of MC1R and Merlin were upregulated after TBI, and activation of MC1R promoted Merlin expression. Further, we found that MC1R activation significantly improved neurological dysfunction and reduced brain edema and neuronal apoptosis induced by TBI in rats. Mechanistically, its neuroprotective function and anti-apoptotic were partly associated with MC1R activation. In conclusion, we demonstrated that MC1R activation after TBI may inhibit apoptosis and confer neuroprotection by upregulating the expression of Merlin.


Asunto(s)
Edema Encefálico , Lesiones Traumáticas del Encéfalo , Animales , Ratas , Apoptosis , Edema Encefálico/etiología , Lesiones Traumáticas del Encéfalo/patología , Genes de la Neurofibromatosis 2 , Neurofibromina 2/genética , Neurofibromina 2/farmacología , Receptor de Melanocortina Tipo 1/genética , Receptor de Melanocortina Tipo 1/metabolismo
16.
Respir Res ; 25(1): 6, 2024 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-38178133

RESUMEN

BACKGROUND: Airway remodeling is a poorly reversible feature of asthma which lacks effective therapeutic interventions. CD147 can regulate extracellular matrix (ECM) remodeling and tissue fibrosis, and participate in the pathogenesis of asthma. In this study, the role of CD147 in airway remodeling and activation of circulating fibrocytes was investigated in asthmatic mice. METHODS: Asthmatic mouse model was established by sensitizing and challenging mice with ovalbumin (OVA), and treated with anti-CD147 or Isotype antibody. The number of eosinophils in bronchoalveolar lavage fluid (BALF) was examined by microscope, and the levels of interleukin-4 (IL-4), IL-5 and IL-13 in BALF were detected by enzyme-linked immunosorbent assay (ELISA). The number of CD45+ and collagen I (COL-I)+ circulating fibrocytes in BALF was detected by flow cytometry. Lung tissue sections were respectively stained with hematoxylin and eosin (HE), periodic acid-Schiff (PAS) or Masson trichrome staining, or used for immunohistochemistry of CD31 and immunohistofluorescence of α-smooth muscle actin (α-SMA), CD45 and COL-I. The protein expression of α-SMA, vascular endothelial growth factor (VEGF), transforming growth factor-ß1 (TGF-ß1), Fibronectin, and COL-I was determined by western blotting. RESULTS: Anti-CD147 treatment significantly reduced the number of eosinophils and the levels of IL-4, IL-13, and IL-5 in BALF, and repressed airway inflammatory infiltration and airway wall thickening in asthmatic mice. Anti-CD147 treatment also reduced airway goblet cell metaplasia, collagen deposition, and angiogenesis in asthmatic mice, accompanied by inhibition of VEGF and α-SMA expression. The number of CD45+COL-I+ circulating fibrocytes was increased in BALF and lung tissues of OVA-induced asthmatic mice, but was decreased by anti-CD147 treatment. In addition, anti-CD147 treatment also reduced the protein expression of COL-I, fibronectin, and TGF-ß1 in lung tissues of asthmatic mice. CONCLUSION: OVA-triggered airway inflammation and airway remodeling in asthmatic mice can be repressed by anti-CD147 treatment, along with inhibiting the accumulation and activation of circulating fibrocytes.


Asunto(s)
Asma , Basigina , Animales , Ratones , Remodelación de las Vías Aéreas (Respiratorias) , Asma/tratamiento farmacológico , Colágeno Tipo I , Fibronectinas , Interleucina-13 , Interleucina-4 , Interleucina-5 , Factor de Crecimiento Transformador beta1 , Factor A de Crecimiento Endotelial Vascular
17.
Mol Med ; 30(1): 4, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38172666

RESUMEN

BACKGROUND: Autophagic defects are involved in Methamphetamine (Meth)-induced neurotoxicity. Syntaxin 17 (Stx17), a member of the SNARE protein family, participating in several stages of autophagy, including autophagosome-late endosome/lysosome fusion. However, the role of Stx17 and potential mechanisms in autophagic defects induced by Meth remain poorly understood. METHODS: To address the mechanism of Meth-induced cognitive impairment, the adenovirus (AV) and adeno-associated virus (AAV) were injected into the hippocampus for stereotaxis to overexpress Stx17 in vivo to examine the cognitive ability via morris water maze and novel object recognition. In molecular level, the synaptic injury and autophagic defects were evaluated. To address the Meth induced neuronal damage, the epidermal growth factor receptor (EGFR) degradation assay was performed to evaluate the degradability of the "cargos" mediated by Meth, and mechanistically, the maturation of the vesicles, including autophagosomes and endosomes, were validated by the Co-IP and the GTP-agarose affinity isolation assays. RESULTS: Overexpression of Stx17 in the hippocampus markedly rescued the Meth-induced cognitive impairment and synaptic loss. For endosomes, Meth exposure upregulated Rab5 expression and its guanine-nucleotide exchange factor (GEF) (immature endosome), with a commensurate decreased active form of Rab7 (Rab7-GTP) and impeded the binding of Rab7 to CCZ1 (mature endosome); for autophagosomes, Meth treatment elicited a dramatic reduction in the overlap between Stx17 and autophagosomes but increased the colocalization of ATG5 and autophagosomes (immature autophagosomes). After Stx17 overexpression, the Rab7-GTP levels in purified late endosomes were substantially increased in parallel with the elevated mature autophagosomes, facilitating cargo (Aß42, p-tau, and EGFR) degradation in the vesicles, which finally ameliorated Meth-induced synaptic loss and memory deficits in mice. CONCLUSION: Stx17 decrease mediated by Meth contributes to vesicle fusion defects which may ascribe to the immature autophagosomes and endosomes, leading to autophagic dysfunction and finalizes neuronal damage and cognitive impairments. Therefore, targeting Stx17 may be a novel therapeutic strategy for Meth-induced neuronal injury.


Asunto(s)
Autofagosomas , Autofagia , Animales , Ratones , Autofagosomas/metabolismo , Endosomas/metabolismo , Receptores ErbB/metabolismo , Factores de Intercambio de Guanina Nucleótido/metabolismo , Guanosina Trifosfato/metabolismo
18.
Am J Surg ; 229: 65-75, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38065723

RESUMEN

BACKGROUND: High rates of postoperative infection persist after different surgical procedures, encompassing surgical site infections (SSIs), remote infections, sepsis, and septic shock. Our aim was to assess presepsin's diagnostic accuracy for postoperative infections in patients across surgical procedures. METHOD: We conducted a comprehensive search in seven databases, extracting data independently. Using STATA 14.0, we calculated pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and Under the receiver operator curve and 95 â€‹% confidence interval (AUC, 95 â€‹% CI) as primary outcomes, with secondary outcomes involving sensitivity and specificity in subgroup analyses. RESULTS: This meta-analysis of 14 studies (1891 cases) evaluated presepsin's diagnostic value for postoperative infectious complications. Results include sensitivity of 77 â€‹% (70-83), specificity of 81 â€‹% (71-88), DOR of 14 (8-26), AUC of 84 (80-87), PLR of 4 (3-6), and NLR of 0.28 (0.21-0.38). Presepsin exhibits promise as a diagnostic tool for postoperative infections. CONCLUSION: In summary, compared to conventional markers like C-reactive protein (CRP) and procalcitonin (PCT), presepsin demonstrated superior sensitivity and specificity for detecting postoperative infectious complications across various surgical procedures.


Asunto(s)
Receptores de Lipopolisacáridos , Sepsis , Humanos , Biomarcadores , Proteína C-Reactiva/metabolismo , Receptores de Lipopolisacáridos/análisis , Fragmentos de Péptidos/análisis , Sepsis/diagnóstico , Sepsis/epidemiología , Sepsis/etiología
19.
World J Clin Cases ; 11(35): 8404-8410, 2023 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-38130615

RESUMEN

BACKGROUND: Phlebosclerosis is a common age-related fibrotic degeneration of the venous wall. It is a disorder rather than a disease, which may cause venous dysfunction and even venous thrombosis. It is rarely reported in patients with varicose veins. CASE SUMMARY: The present report describes the case of a 70-year-old man with varicose veins, vitiligo, and phlebosclerosis. Venous angiography revealed blood reflux in the superficial and deep veins. The patient underwent surgery to remove the saphenous veins. During the operation, a calcified vein resembling a wooden stick was found, which was surprisingly extracted from the thickened venous wall. A cross-section of this wooden stick-like vein revealed venous fibrosis and calcification, obvious thickening of the venous wall, extensive collagen deposition on the venous wall, hyaline degeneration, and venous sclerosis causing closure of the venous lumen. CONCLUSION: This is probably the first report of a wooden stick-like structure being found in the venous wall in patients with varicose veins and venous ulcers. Phlebosclerosis can be observed in the late stage of varicose veins complicated by frequent infections and worse clinical outcomes. Therefore, it is important to be aware of this condition and address it rather than overlook it.

20.
Ann Med Surg (Lond) ; 85(11): 5538-5549, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37915709

RESUMEN

Background: Bacterial biofilms, which can protect bacteria from host immune response and drug attack, are an important factor in the difficult healing of chronic wound infection, which has become a major problem in medical development. This paper aimed to analyze literature related to bacterial biofilm wound treatment published between 2012 and 2022 using bibliometric and visual analysis. Methods: Publications related to bacterial biofilm wound treatment from 2012 to 2022 were selected from the Web of Science Core Collection. Microsoft Excel 2021, bibliometrics, CiteSpace6.1, and VOSviewer1.6.18 were used to extract and analyze data. Results: A total of 940 articles were published between 2012 and 2022, with the United States being the leading country (with 302 papers, 32.13%) and the University of Copenhagen in Denmark being the leading institution (with 26 published articles) in the field. Steven L Percival, a British academic, published the most articles (14). In the field of bacterial biofilm wound treatment, keywords suggested that the research gradually transitioned from lower limb venous ulcer, negative pressure-assisted healing to chronic wound, in-vitro bacterial biological model research, and then to the development of more microscopic and more advanced technologies such as antibacterial activity and nanomaterials. "Nanoparticles", "inhibition/antibacterial", "delivery", "gold nanoparticles", "hydrogel", "wound healing", etc., may become new research hotspots in this field. Conclusion: There is a lack of specific and effective treatment methods for diagnosing and treating bacterial biofilms in wounds. Through the development of multidisciplinary cooperation, early diagnosis and treatment of bacterial biofilms in wounds can be achieved. These data may provide a useful reference for scholars studying more effective bacterial biofilm wound treatment.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA