Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 864
Filtrar
1.
Proc Natl Acad Sci U S A ; 121(37): e2408716121, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39226360

RESUMEN

Bacterial evolution, particularly in hospital settings, is leading to an increase in multidrug resistance. Understanding the basis for this resistance is critical as it can drive discovery of new antibiotics while allowing the clinical use of known antibiotics to be optimized. Here, we report a photoactive chemical probe for superresolution microscopy that allows for the in situ probing of antibiotic-induced structural disruption of bacteria. Conjugation between a spiropyran (SP) and galactose via click chemistry produces an amphiphilic photochromic glycoprobe, which self-assembles into glycomicelles in water. The hydrophobic inner core of the glycomicelles allows encapsulation of antibiotics. Photoirradiation then serves to convert the SP to the corresponding merocyanine (MR) form. This results in micellar disassembly allowing for release of the antibiotic in an on-demand fashion. The glycomicelles of this study adhere selectively to the surface of a Gram-negative bacterium through multivalent sugar-lectin interaction. Antibiotic release from the glycomicelles then induces membrane collapse. This dynamic process can be imaged in situ by superresolution spectroscopy owing to the "fluorescence blinking" of the SP/MR photochromic pair. This research provides a high-precision imaging tool that may be used to visualize how antibiotics disrupt the structural integrity of bacteria in real time.


Asunto(s)
Antibacterianos , Benzopiranos , Indoles , Antibacterianos/farmacología , Antibacterianos/química , Benzopiranos/química , Benzopiranos/farmacología , Indoles/química , Micelas , Nitrocompuestos/química , Pirimidinonas/química , Pirimidinonas/farmacología
2.
J Phys Chem A ; 128(32): 6729-6738, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39109870

RESUMEN

This study elucidates the mechanisms and principles governing chemoselectivity in synthesizing two distinct N-heterocycles, benzimidazole thiazine and benzothiazole imidazole, through BF3•OEt2-catalyzed cyclization reactions of propargyl alcohols with benzimidazole thiols. Employing density functional theory calculations, we highlight the crucial role of fluorine source in influencing chemoselectivity. In DCM, BF3, as the catalytic center, coordinates with propargyl alcohol's hydroxyl group to form a precursor. Conversely, in DMF, [BF2•DMF]+, formed from DMF and BF3•OEt2, acts as the catalytic center, activating the propargyl alcohol's hydroxyl group. The mechanisms in both solvents involve sequential steps: B-O bond formation, C-O bond cleavage, S-C bond formation, hydrogen atom transfer (HAT), cyclization, and deprotonation. A notable difference is the HAT process: in DCM, it follows a 1,5-HAT process, while in DMF, BF4- formation from DMF and BF3•OEt2 provides a fluorine source and introduces steric hindrance, favoring a 1,6-HAT process and leading to unique chemoselectivity. This pioneering research showcases the impact of DMF on cyclization reactions, offering valuable insights for comprehending and designing reactions driven by fluorine sources. Crucially, our results propose an innovative reaction mechanism featuring lower potential energy surfaces, enhancing our understanding of the intricate interplay among reactants, catalysts, and solvents.

3.
PLoS One ; 19(8): e0308172, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39088487

RESUMEN

BACKGROUND: Meal timing has been associated with metabolism and cardiovascular diseases; however, the relationship between meal timing and sleep quality remains inconclusive. OBJECTIVE: This study aims to investigate the relationship between meal timing and sleep quality from a chronobiological perspective. METHODS: This study utilized data from the NHANES for the years 2005-2008, including a cohort of 7,023 participants after applying exclusion criteria. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Meal timing was analyzed based on two 24-hour dietary recalls from each individual, considering the timing of the initial and final meals, meal duration, and frequency of meal occasions. Multiple linear regression models and hierarchical analyses were employed to examine the relationship between meal timing and PSQI scores, adjusting for various demographic and habitat covariates. RESULTS: Statistical analysis revealed a positive correlation between delayed meal timings, increased meal occasions, and elevated PSQI scores, indicating that later meal timing are intricately linked with diminished sleep quality. Both later meal timings and more frequent meal occasions were significantly associated with poorer sleep quality. Compared to the first tertile, the ß (95%CI) values of the third tertile were 0.545 (0.226, 0.864) for first meal timing, 0.586 (0.277, 0.896) for midpoint meal timing, 0.385 (0.090, 0.680) for last meal timing, and 0.332 (0.021, 0.642) for meal occasions in the adjusted models. CONCLUSION: These findings suggest that late initial, midpoint, and final meal timing, as well as more frequent meal occasions, are chrono-nutrition patterns associated with poor sleep quality.


Asunto(s)
Comidas , Calidad del Sueño , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Conducta Alimentaria/fisiología , Factores de Tiempo , Encuestas Nutricionales , Ritmo Circadiano/fisiología , Sueño/fisiología
4.
Chem Commun (Camb) ; 60(72): 9801-9804, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39162090

RESUMEN

A metal-free and sustainable visible-light-mediated method for the preparation of organic nitrate esters has been developed through the aerobic nitrooxylation reaction of α-diazoesters and cyclic ethers with t-BuONO in the presence of dioxygen. This protocol provides an efficient approach to access nitrate esters with the advantages of clean energy, broad substrate scope, green oxidants, operational simplicity, and mild conditions.

5.
Artículo en Inglés | MEDLINE | ID: mdl-39032670

RESUMEN

BACKGROUND: In a gene expression analysis comparing sinus mucosa samples from allergic fungal rhinosinusitis (AFRS) patients with samples from non-AFRS chronic rhinosinusitis with nasal polyp (CRSwNP) patients, the antimicrobial peptide (AMP) histatin 1 (HTN1) was found to be the most differentially downregulated gene in AFRS. OBJECTIVE: We sought to identify the molecular etiology of the downregulated expression of HTN1. METHODS: We used RT-PCR to compare the expression of AMPs and a fungistasis assay to evaluate the antifungal activity of sinus secretions. Using flow cytometry, we characterized the presence of TH17/TH22 cells and signal transducer and activator of transcription (STAT) signaling from AFRS patients, non-AFRS CRSwNP patients, and healthy controls. RESULTS: We confirmed decreased expression of AMPs in AFRS sinus mucosa with concordant decrease in antifungal activity in sinus secretions. IL-22 and IL-22-producing T cells were deficient within sinus mucosa of AFRS patients. In vitro studies demonstrated a defect in IL-6/STAT3 signaling critical for TH17/TH22 differentiation. Epithelial cells from AFRS patients could express AMPs when stimulated with exogenous IL-22/IL-17 and circulating TH17 cell abundance was normal. CONCLUSIONS: Similar to other hyper-IgE syndromes, but distinct from CRSwNP, AFRS patients express a defect in STAT3 activation limited to IL-6-dependent STAT3 phosphorylation that is critical for TH17/TH22 differentiation. This defect leads to a local deficiency of IL-17/IL-22 cytokines and deficient AMP expression within diseased sinus mucosa of AFRS patients. Our findings support evaluation of therapeutic approaches that enhance airway AMP production in AFRS.

6.
J Org Chem ; 89(15): 10974-10986, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39048291

RESUMEN

Visible-light photoredox-catalyzed method has been developed for the synthesis of quinoxalin-2(1H)-one-containing vinyl phosphorodithioates via direct difunctionalization of alkynes with quinoxalin-2(1H)-ones, P4S10 and alcohols. This four-component reaction could be carried out under metal-free and mild conditions, affording a number of quinoxalin-2(1H)-one-containing vinyl phosphorodithioates in moderate to good yields with Z-isomers as the major products. Photocatalytic radical mechanism is proposed based on the results of radical trapping and fluorescence quenching experiments.

7.
Adv Mater ; 36(36): e2403228, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39022846

RESUMEN

This study investigates the impact of In- and S-vacancy concentrations on the photocatalytic activity of non-centrosymmetric zinc indium sulfide (ZIS) nanosheets for the hydrogen evolution reaction (HER). A positive correlation between the concentrations of dual In and S vacancies and the photocatalytic HER rate over ZIS nanosheets is observed. The piezoelectric polarization, stimulated by low-frequency vortex vibration to ensure the well-dispersion of ZIS nanosheets in solution, plays a crucial role in enhancing photocatalytic HER over the dual-vacancy engineered ZIS nanosheets. The piezoelectric characteristic of the defective ZIS nanosheets is confirmed through the piezopotential response measured using piezoelectric force microscopy. Piezophotocatalytic H2 evolution over the ZIS nanosheets is boosted under accelerated vortex vibrations. The research explores how vacancies alter ZIS's dipole moment and piezoelectric properties, thereby increasing electric potential gradient and improving charge-separation efficiency, through multi-scale simulations, including Density Functional Theory and Finite Element Analysis, and a machine-learning interatomic potential for defect identification. Increased In and S vacancies lead to higher electric potential gradients in ZIS along [100] and [010] directions, attributing to dipole moment and the piezoelectric effect. This research provides a comprehensive exploration of vacancy engineering in ZIS nanosheets, leveraging the piezopotential and dipole field to enhance photocatalytic performances.

8.
J Transl Int Med ; 12(3): 288-298, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39081282

RESUMEN

Background and Objectives: Overcoming ATP-binding cassette subfamily G member 2 (ABCG2)-mediated multidrug resistance (MDR) has attracted the attention of scientists because one of the critical factors resulting in MDR in cancer is the overexpression of ABCG2. RN486, a Bruton's Tyrosine Kinase (BTK) inhibitor, was discovered to potentially reverse ABCB1-mediated MDR. However, there is still uncertainty about whether RN486 has a reversal off-target impact on ABCG2-mediated MDR. Methods: MTT assay was used to detect the reversal effect of RN486 on ABCG2-overexpressing cancer cells. The ABCG2 expression level and subcellular localization were examined by Western blotting and immunofluorescence. Drug accumulation and eflux assay and ATPase assay were performed to analyze the ABCG2 transporter function and ATPase activity. Molecular modeling predicted the binding between RN486 and ABCG2 protein. Results: Non-toxic concentrations of RN486 remarkably increased the sensitivity of ABCG2-overexpressing cancer cells to conventional anticancer drugs mitoxantrone and topotecan. The reversal mechanistic studies showed that RN486 elevated the drug accumulation because of reducing the eflux of ABCG2 substrate drug in ABCG2-overexpressing cancer cells. In addition, the inhibitory efect of RN486 on ABCG2-associated ATPase activity was also verified. Molecular docking study implied a strong binding afinity between RN486 and ABCG2 transporter. Meanwhile, the ABCG2 subcellular localization was not altered by the treatment of RN486, but the expression level of ABCG2 was down-regulated. Conclusions: Our studies propose that RN486 can antagonize ABCG2-mediated MDR in cancer cells via down-regulating the expression level of ABCG2 protein, reducing ATPase activity of ABCG2 transporter, and inhibiting the transporting function. RN486 could be potentially used in conjunction with chemotherapy to alleviate MDR mediated by ABCG2 in cancer.

9.
Nanomaterials (Basel) ; 14(12)2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38921909

RESUMEN

Rapid advancements in nanotechnology have expanded its applications and synergistic impact on modern nanosystems. The comprehensive assessment of nanomaterials' safety for human exposure has become crucial and heightened. In addition to the characterization of cell proliferation and apoptosis, probing the implication of autophagy is vital for understanding the ramification of nanomaterials. Hence, HEK-293 kidney cells were employed to understand the changes in induction and perturbation of autophagy in cells by iron oxide (Fe3O4) and silica (SiO2) nanoparticles. Interestingly, Fe3O4 worked as a potent modulator of the autophagy process through its catalytic performance, which can develop better than that of SiO2 nanoparticles mechanism, stressing their therapeutic implication in the understanding of cell behaviors. The quantification of reactive oxygen species (ROS) was measured along with the process of autophagy during cell growth. This modulated autophagy will help in cell fate determination in complementary therapy for disease treatment, provide a clinical strategy for future study.

10.
Mitochondrial DNA B Resour ; 9(6): 720-724, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38859915

RESUMEN

Polygonatum hunanense H.H. Liu & B.Z. Wang (2021) and P. verticillatum (L.) All. (1875) have been widely used as foods and as folk medicines in China and India, and P. caulialatum S. R. Yi (2021) has recently been described as a new medical plant in China. There is at present a lack of genome information regarding the species. Hence, this study reports the complete chloroplast genomes of the three species. The genomes of P. hunanense, P. verticillatum, and P. caulialatum were 155,583 bp, 155,650 bp, and 155,352 bp in length, respectively. They contained large single-copy (LSC) regions of 84,412 bp, 84,404 bp, and 84,285 bp, small single-copy (SSC) regions of 18,427 bp, 18,416 bp, and 18,463 bp, and a pair of inverted repeats of 26,372 bp, 26,415 bp, and 26,302 bp, respectively. The chloroplast genomes of P. hunanense, P. verticillatum, and P. caulialatum had 133 (103 unique) genes, consisting of 87 protein-coding genes, 38 ribosomal ribonucleic acid (RNA) genes, and eight transfer RNA genes, respectively. A maximum-likelihood phylogenetic tree showed that P. kingianum Coll. et Hemsl. var. grandifolium D.M. Liu & W.Z. Zeng (1991) was closer to P. cyrtonema Hua (1892) rather than to P. kingianum Coll. et Hemsl. (1890), further supporting its status as a unique species of the genus. Moreover, P. verticillatum was separated from the easily confused herb P. cirrhifolium (Wall.) Royle (1839), while P. caulialatum was closest to P. humile Fisch. ex Maxim. (1859). This research provides a foundation for further study of these herbs.

11.
Bioanalysis ; 16(8): 179-220, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38899739

RESUMEN

The 17th Workshop on Recent Issues in Bioanalysis (17th WRIB) took place in Orlando, FL, USA on 19-23 June 2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 17th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.Moreover, in-depth workshops on "EU IVDR 2017/746 Implementation and impact for the Global Biomarker Community: How to Comply with these NEW Regulations" and on "US FDA/OSIS Remote Regulatory Assessments (RRAs)" were the special features of the 17th edition.As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues.This 2023 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2023 edition of this comprehensive White Paper has been divided into three parts for editorial reasons.This publication (Part 2) covers the recommendations on Biomarkers, IVD/CDx, LBA and Cell-Based Assays. Part 1A (Mass Spectrometry Assays and Regulated Bioanalysis/BMV), P1B (Regulatory Inputs) and Part 3 (Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity) are published in volume 16 of Bioanalysis, issues 9 and 7 (2024), respectively.


Asunto(s)
Biomarcadores , Tratamiento Basado en Trasplante de Células y Tejidos , Vacunas , Humanos , Biomarcadores/análisis , Vacunas/inmunología , Citometría de Flujo , Bioensayo/métodos , Unión Europea , Blanco
12.
Virulence ; 15(1): 2350892, 2024 12.
Artículo en Inglés | MEDLINE | ID: mdl-38745370

RESUMEN

The evasive tactics of Treponema pallidum pose a major challenge in combating and eradicating syphilis. Natural killer (NK) cells mediate important effector functions in the control of pathogenic infection, preferentially eliminating targets with low or no expression of major histocompatibility complex (MHC) class I. To clarify T. pallidum's mechanisms in evading NK-mediated immunosurveillance, experiments were performed to explore the cross-talk relations among T. pallidum, NK cells, and platelets. T. pallidum adhered to, activated, and promoted particle secretion of platelets. After preincubation with T. pallidum, platelets expressed and secreted high levels of MHC class I, subsequently transferring them to the surface of T. pallidum, potentially inducing an immune phenotype characterized by the "pseudo-expression" of MHC class I on the surface of T. pallidum (hereafter referred to a "pseudo-expression" of MHC class I). The polA mRNA assay showed that platelet-preincubated T. pallidum group exhibited a significantly higher copy number of polA transcript than the T. pallidum group. The survival rate of T. pallidum mirrored that of polA mRNA, indicating that preincubation of T. pallidum with platelets attenuated NK cell lethality. Platelets pseudo-expressed the MHC class I ligand on the T. pallidum surface, facilitating binding to killer cell immunoglobulin-like receptors with two immunoglobulin domains and long cytoplasmic tail 3 (KIR2DL3) on NK cells and initiating dephosphorylation of Vav1 and phosphorylation of Crk, ultimately attenuating NK cell lethality. Our findings elucidate the mechanism by which platelets transfer MHC class I to the T. pallidum surface to evade NK cell immune clearance.


Asunto(s)
Plaquetas , Antígenos de Histocompatibilidad Clase I , Células Asesinas Naturales , Sífilis , Treponema pallidum , Células Asesinas Naturales/inmunología , Treponema pallidum/inmunología , Treponema pallidum/genética , Humanos , Plaquetas/inmunología , Plaquetas/microbiología , Antígenos de Histocompatibilidad Clase I/inmunología , Sífilis/inmunología , Sífilis/microbiología , Evasión Inmune
13.
Medicine (Baltimore) ; 103(21): e38254, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38788021

RESUMEN

Cerebral collateral circulation (CC) is associated with the recurrence and severity of acute ischemic stroke (AIS), and early identification of poor CC is helpful for the prevention of AIS. In this study we evaluated the association between serum albumin levels and CC in AIS using logistic regression. Propensity score (PS) matching was used to eliminate the effect of confounders, and restricted cubic splines (RCS) were employed to explore potential nonlinear associations between albumin and CC. In unadjusted logistic regression analysis, lower albumin (OR = 0.85, 95% CI = 0.79-0.92) was associated with poor CC, and after adjusting for covariates, the odds of lower albumin for poor CC compared to good CC were 0.86 (95% CI = 0.79-0.94). In the PS cohort, the association of albumin with CC was consistent with those of the original cohort. RCS results showed a linear relationship between albumin and CC (P values of .006 and .08 for overall and nonlinear associations, respectively). The results of this study suggest that lower serum albumin is independently associated with an increased risk of poor CC, which may serve as an effective predictive indicator for poor CC in patients with severe intracranial atherosclerotic stenosis.


Asunto(s)
Circulación Colateral , Accidente Cerebrovascular Isquémico , Puntaje de Propensión , Albúmina Sérica , Humanos , Masculino , Circulación Colateral/fisiología , Femenino , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/fisiopatología , Accidente Cerebrovascular Isquémico/etiología , Persona de Mediana Edad , Anciano , Albúmina Sérica/análisis , Circulación Cerebrovascular/fisiología , Arteriosclerosis Intracraneal/sangre , Arteriosclerosis Intracraneal/fisiopatología , Arteriosclerosis Intracraneal/complicaciones , Estudios Retrospectivos , Modelos Logísticos
15.
PLoS One ; 19(5): e0299664, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38748654

RESUMEN

The specific emitter identification is widely used in electronic countermeasures, spectrum control, wireless network security and other civil and military fields. In response to the problems that the traditional specific emitter identification algorithm relies on a priori knowledge and has poor generalizability, and the existing specific emitter identification algorithm based on deep learning has poor feature selection and the adopted feature extraction network is not targeted, etc., the specific emitter identification algorithm based on multi-sequence feature learning is proposed. Firstly, multiple sequence features of the emitted signal of the communication radiation source are extracted, and these features are combined into multiple sequence features. Secondly, the multiple sequence fusion convolutional network is constructed to fuse and deeply extract the multiple sequence features and complete the classification of individual communication radiation sources through the classifier of neural network. The selected sequence features of this algorithm contain more and more essential RFF information, while the targeted design of the multi-sequence feature fusion learning network can effectively extract the essential RFF information. The results show that the algorithm can significantly improve the performance of SEI compared with the benchmark algorithm, with a recognition rate gain of about 17%.


Asunto(s)
Algoritmos , Redes Neurales de la Computación , Aprendizaje Profundo
16.
Sci Rep ; 14(1): 11486, 2024 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-38769368

RESUMEN

The purpose of this study was to investigate the relationship between circulating cytokines and liver function and prognosis of patients with advanced hepatocellular carcinoma (HCC) treated with radiotherapy combined with tislelizumab and anlotinib. The liver function indexes and pre-treatment levels of cytokines in 47 patients were measured by chemical method and flow cytometry. The median follow-up was 23.1 months. The objective response and the disease control rates were 46.8% and 68.1%, while overall survival (OS) and progression-free survival (PFS) were 12.6 and 11.4 months, respectively. Adverse events (2.1%) were grade 3-4. In addition to stage, intrahepatic metastasis and Child-Pugh score, pre-treatment interleukin-6 (IL-6) was the main cytokine affecting OS and PFS (p < 0.05). The OS (14.63 pg/mL as cutoff value) and PFS (9.85 pg/mL as cutoff value) of patients with low IL-6 levels exceeded those with high levels (21.0 and 6.9, 15.8 and 10.0 months, respectively). The risks of death and disease progression were reduced by 63.0% (HR = 0.37, 95% CI: 0.19-0.72) and 43.0% (HR = 0.57, 95% CI: 0.22-1.47), respectively. Pre-treatment IL-6 levels may be a simple and effective prognostic indicator for patients with advanced HCC treated with radiotherapy combined with immunotargeted therapy.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Carcinoma Hepatocelular , Citocinas , Indoles , Neoplasias Hepáticas , Quinolinas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anciano , Indoles/uso terapéutico , Indoles/administración & dosificación , Pronóstico , Citocinas/sangre , Adulto , Interleucina-6/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
17.
Artículo en Inglés | MEDLINE | ID: mdl-38767671

RESUMEN

Activation of the renin-angiotensin system (RAS) triggers oxidative stress and an inflammatory response in the hypothalamic paraventricular nucleus (PVN), in turn increasing the sympathetic hyperactivity that is a major cause of hypertension. Pyridostigmine has cardioprotective effects by suppressing the RAS of myocardial tissue. However, whether pyridostigmine attenuates hypertension by inhibiting the RAS of the PVN remains unclear. We thus investigated the effect and mechanism of pyridostigmine on two-kidney one-clip (2K1C)-induced hypertension. 2K1C rats received pyridostigmine, or not, for 8 weeks. Cardiovascular function, hemodynamic parameters, and autonomic activity were measured. The PVN levels of pro-/anti-inflammatory cytokines, oxidative stress, and RAS signaling molecules were evaluated. Our results showed that hypertension was accompanied by cardiovascular dysfunction and an autonomic imbalance characterized by enhanced sympathetic but diminished vagal activity. The PVN levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS), NOX-2, and malondialdehyde (MDA) increased; those of IL-10 and superoxide dismutase (SOD) decreased. Moreover, the RAS signaling pathway was activated, as evidenced by increased levels of the angiotensin-converting enzyme (ACE), angiotensin II (Ang II), and the Ang II type 1 receptor (AT1R) and a decreased AT2R level. Pyridostigmine lowered blood pressure and improved cardiovascular function, associated with restoration of the autonomic balance. Meanwhile, pyridostigmine decreased PVN IL-6, TNF-α, ROS, NOX-2, and MDA levels and increased IL-10 and SOD levels. Additionally, pyridostigmine suppressed PVN ACE, Ang II, and AT1R levels and increased AT2R expression. Pyridostigmine attenuated hypertension by inhibiting PVN oxidative stress and inflammation induced by the RAS.

18.
Org Lett ; 26(18): 3883-3888, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38683041

RESUMEN

A (2,2,6,6-tetramethylpiperidin-1-yl)oxyl-mediated difunctionalization of alkenes with tert-butyl nitrite, P4S10, and alcohols has been developed for the synthesis of ß-oximino phosphorodithioates. The reaction goes through a radical pathway with the successive installation of phosphorodithioate and an oxime group. This four-component protocol offers a practical approach to constructing a variety of ß-oximino phosphorodithioates in moderate to good yields with favorable functional group tolerance.

19.
J Cell Mol Med ; 28(8): e18356, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38668995

RESUMEN

Trichospira verticillata is an annual herb that belongs to the family Asteraceae. Trichospira verticillata extract (TVE) elicits anti-plasmodial activity; however, there has been no detailed report about its anti-inflammatory effects and molecular mechanisms. In addition, herbal plants exhibit anti-inflammatory effects by suppressing the NLRP3 inflammasome. Therefore, the primary goal of this study was to examine the effects of TVE on NLRP3 inflammasome activation by measuring interleukin-1ß (IL-1ß) secretion. We treated lipopolysaccharides (LPS)-primed J774A.1 and THP-1 cells with TVE, which attenuated NLRP3 inflammasome activation. Notably, TVE did not affect nuclear factor-kappa B (NF-κB) signalling or intracellular reactive oxygen species (ROS) production and potassium efflux, suggesting that it inactivates the NLRP3 inflammasome via other mechanisms. Moreover, TVE suppressed the formation of apoptosis-associated speck-like protein (ASC) speck and oligomerization. Immunoprecipitation data revealed that TVE reduced the binding of NLRP3 to NIMA-related kinase 7 (NEK7), resulting in reduced ASC oligomerization and speck formation. Moreover, TVE alleviated neutrophilic asthma (NA) symptoms in mice. This study demonstrates that TVE modulates the binding of NLPR3 to NEK7, thereby reporting novel insights into the mechanism by which TVE inhibits NLRP3 inflammasome. These findings suggest TVE as a potential therapeutic of NLRP3 inflammasome-mediated diseases, particularly NA.


Asunto(s)
Antiinflamatorios , Asma , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Neutrófilos , Especies Reactivas de Oxígeno , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Animales , Inflamasomas/metabolismo , Asma/metabolismo , Asma/tratamiento farmacológico , Asma/inmunología , Asma/patología , Ratones , Antiinflamatorios/farmacología , Humanos , Neutrófilos/metabolismo , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Especies Reactivas de Oxígeno/metabolismo , Lipopolisacáridos , Quinasas Relacionadas con NIMA/metabolismo , Interleucina-1beta/metabolismo , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Modelos Animales de Enfermedad , Extractos Vegetales/farmacología , Células THP-1
20.
Int J Mol Sci ; 25(6)2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38542240

RESUMEN

The synergistic impact of nanomaterials is critical for novel intracellular and/or subcellular drug delivery systems of minimal toxicity. This synergism results in a fundamental bio/nano interface interaction, which is discussed in terms of nanoparticle translocation, outer wrapping, embedding, and interior cellular attachment. The morphology, size, surface area, ligand chemistry and charge of nanoparticles all play a role in translocation. In this review, we suggest a generalized mechanism to characterize the bio/nano interface, as we discuss the synergistic interaction between nanoparticles and cells, tissues, and other biological systems. Novel perceptions are reviewed regarding the ability of nanoparticles to improve hybrid nanocarriers with homogeneous structures to enhance multifunctional biomedical applications, such as bioimaging, tissue engineering, immunotherapy, and phototherapy.


Asunto(s)
Nanopartículas , Nanoestructuras , Nanopartículas/química , Nanoestructuras/química , Sistemas de Liberación de Medicamentos/métodos , Ingeniería de Tejidos , Propiedades de Superficie
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA