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1.
Angew Chem Int Ed Engl ; : e202417362, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39278829

RESUMEN

Imide functionalization has been widely proved to be an effective approach to enrich optoelectronic properties of polycyclic aromatic hydrocarbons (PAHs). However, appending multiple imide groups onto linear acenes is still a synthetic challenge. Herein, we demonstrate that by taking advantage of a "breaking and mending" strategy, a linear pentacene tetraimides (PeTI) was synthesized through a three-step sequence started from the naphthalene diimides (NDI). Compared with the parent pentacene, PeTI shows a deeper-lying lowest unoccupied molecular orbital (LUMO) energy level, narrower bandgap and better stability. The redox behavior of PeTI was firstly evaluated by generating a stable radical anion specie with the assistance of cobaltocene (CoCp2), and the structure of the electron transfer (ET) complex was confirmed by the X-ray crystallography. Moreover, due to the presence of multiple redox-active sites, we are able to show that the state-of-the-art energy storage performance of the dealkylated PeTI (designated as PeTCTI) in organic potassium ion batteries (OPIBs) as an anode. Our results shed light on the application of multiple imides functionalized linear acenes, and the reported synthetic strategy provides an effective way to get access to longer nanoribbon imides with fascinating electronic properties.

2.
Int J Biol Macromol ; 279(Pt 3): 135307, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39236940

RESUMEN

The alternative sigma factor RpoS functions as a regulator of stress and virulence response in numerous bacterial species. Vibrio mimicus is a critical opportunistic pathogen causing huge losses to aquaculture. However, the exact role of RpoS in V. mimicus remains unclear. In this study, rpoS deletion mutant of V. mimicus was constructed through allelic exchange and the phenotypic and transcriptional changes were investigated to determine the function of RpoS. The abilities of growth, motility, biofilm production, hemolytic activity and pathogenicity were significantly impaired in ΔrpoS strain. Stationary-phase cells of ΔrpoS strain showed lower tolerance to H2O2, heat, ethanol, and starvation stress than the wild-type strain. Transcriptome analyses revealed the involvement of rpoS in various cellular processes, notably bacterial-type flagellum synthesis and assembly, membrane synthesis and assembly and response to various stimuli. Phenotypic and RNA-seq analysis revealed that RpoS is required for biofilm formation, stress resistance, and pathogenicity in V. mimicus. Furthermore, ß-galactosidase activity showed that rpoS is essential for optimal transcription of the flgK, fliA, cheA, mcpH mRNA. These results offer significant insight into the function and regulatory network of rpoS/RpoS, thereby improving our understanding and facilitating selection of molecular targets for future prevention strategies against V. mimicus.

3.
Microbiome ; 12(1): 161, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39223641

RESUMEN

BACKGROUND: Many studies have demonstrated the association between intestinal microbiota and joint diseases. The "gut-joint axis" also has potential roles in chikungunya virus (CHIKV) infection. Pro-inflammatory arthritis after CHIKV infection might disrupt host homeostasis and lead to dysbacteriosis. This study investigated the characteristics of fecal and gut microbiota, intestinal metabolites, and the changes in gene regulation of intestinal tissues after CHIKV infection using multi-omics analysis to explore the involvement of gut microbiota in the pathogenesis of CHIKV infection. RESULTS: CHIKV infection increases the systemic burden of inflammation in the GI system of infected animals. Moreover, infection-induced alterations in GI microbiota and metabolites may be indirectly involved in the modulation of GI and bone inflammation after CHIKV infection, including the modulation of inflammasomes and interleukin-17 inflammatory cytokine levels. CONCLUSION: Our results suggest that the GI tract and its microbes are involved in the modulation of CHIKV infection, which could serve as an indicator for the adjuvant treatment of CHIKV infection. Video Abstract.


Asunto(s)
Fiebre Chikungunya , Virus Chikungunya , Heces , Microbioma Gastrointestinal , Macaca mulatta , Animales , Heces/microbiología , Fiebre Chikungunya/virología , Bacterias/clasificación , Bacterias/metabolismo , Bacterias/aislamiento & purificación , Bacterias/genética , Disbiosis/microbiología , Inflamación , Inflamasomas/metabolismo , Modelos Animales de Enfermedad , Interleucina-17/metabolismo , Tracto Gastrointestinal/microbiología , Citocinas/metabolismo
4.
Cancers (Basel) ; 16(17)2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39272847

RESUMEN

Tyrosine kinase inhibitors (TKIs) represent a relatively large class of small-molecule inhibitors that compete with ATP for the catalytic binding site of tyrosine kinase proteins. While TKIs have demonstrated effectiveness in the treatment of multiple malignancies, including chronic myelogenous leukemia, gastrointestinal tumors, non-small cell lung cancers, and HER2-overexpressing breast cancers, as is almost always the case with anti-neoplastic agents, the development of resistance often imposes a limit on drug efficacy. One common survival response utilized by tumor cells to ensure their survival in response to different stressors, including anti-neoplastic drugs, is that of autophagy. The autophagic machinery in response to TKIs in multiple tumor models has largely been shown to be cytoprotective in nature, although there are a number of cases where autophagy has demonstrated a cytotoxic function. In this review, we provide an overview of the literature examining the role that autophagy plays in response to TKIs in different preclinical tumor model systems in an effort to determine whether autophagy suppression or modulation could be an effective adjuvant strategy to increase efficiency and/or overcome resistance to TKIs.

5.
ACS Nano ; 18(37): 25671-25684, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39223995

RESUMEN

Combined photodynamic and photothermal therapy (PDT and PTT) can achieve more superior therapeutic effects than the sole mode by maximizing the photon utilization, but there remains a significant challenge in the development of related single-molecule photosensitizers (PSs), particularly those with type I photosensitization. In this study, self-assembly of squaraine dyes (SQs) is shown to be a promising strategy for designing PSs for combined type I PDT and PTT, and a supramolecular PS (TPE-SQ7) has been successfully developed through subtle molecular design of an indolenine SQ, which can self-assemble into highly ordered H-aggregates in aqueous solution as well as nanoparticles (NPs). In contrast to the typical quenching effect of H-aggregates on reactive oxygen species (ROS) generation, our results encouragingly manifest that H-aggregates can enhance type I ROS (•OH) generation by facilitating the intersystem crossing process while maintaining a high PTT performance. Consequently, TPE-SQ7 NPs with ordered H-aggregates not only exhibit superior combined therapeutic efficacy than the well-known PS (Ce6) under both normoxic and hypoxic conditions but also have excellent biosafety, making them have important application prospects in tumor phototherapy and antibacterial fields. This study not only proves that the supramolecular self-assembly of SQs is an effective strategy toward high-performance PSs for combined type I PDT and PTT but also provides a different understanding of the effect of H-aggregates on the PDT performance.


Asunto(s)
Ciclobutanos , Fenoles , Fotoquimioterapia , Fármacos Fotosensibilizantes , Terapia Fototérmica , Especies Reactivas de Oxígeno , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Humanos , Ciclobutanos/química , Ciclobutanos/farmacología , Fenoles/química , Fenoles/farmacología , Especies Reactivas de Oxígeno/metabolismo , Ratones , Animales , Supervivencia Celular/efectos de los fármacos , Nanopartículas/química , Antineoplásicos/química , Antineoplásicos/farmacología , Sustancias Macromoleculares/química , Sustancias Macromoleculares/farmacología , Sustancias Macromoleculares/síntesis química
6.
Front Pharmacol ; 15: 1413154, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39314755

RESUMEN

Objective: To investigate the potential association between tumor lysis syndrome (TLS) and drugs for the treatment of malignant melanoma (MM). Methods: Reports of TLS recorded in the FDA Adverse Event Reporting System (FAERS) (January 2004-2023q3) were identified. Demographic and clinical characteristics were described, and disproportionality signals were assessed through the Reporting Odds Ratio (ROR) and Information Component (IC). The latency of TLS with anticancer drugs was described based on parametric models. Subgroup analysis was conducted to explore the differences of TLS signals in different age and sex. Results: We found 5 (1.49%), 59 (17.61%), 79 (23.58%), 19 (5.67%), 13 (3.88%), 13 (3.88%), 33 (9.85%), 49 (14.63%), 16 (4.78%) TLS reports with pembrolizumab, nivolumab, ipilimumab, dabrafenib, vemurafenib, dacarbazine, "encorafenib and binimetinib", "nivolumab and ipilimumab", "dabrafenib and trametinib", respectively. The combination of encorafenib and binimetinib showed the strongest signal of TLS (IC025 = 3.98). The median days of latency of TLS with combination of encorafenib and binimetinib is 2 days, which was much shorter than nivolumab (22.0 days) and ipilimumab (21.5 days). TLS cases associated with drugs for MM were predominantly recorded in females and aged 25-65 years. After excluding confounding factors such as pre-existing diseases and co-treated drugs, the disproportionate signal of TLS with "encorafenib and binimetinib" remained strong. Conclusions: Stronger disproportionate signal of TLS was detected in MM patients using the combination of encorafenib and binimetinib than other drugs. Further research is needed to investigate the underlying mechanisms and identify patient-related predisposing factors to support safe prescribing of the combination of encorafenib and binimetinib.

7.
Ann Surg Treat Res ; 107(2): 68-80, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39139830

RESUMEN

Purpose: This study was performed to investigate influencing factors of preoperative muscle mass-to-fat ratio (MMFR) and its impact on overall survival and postoperative complications of colon cancer. Methods: Patients who underwent colectomy for stage I-III colon cancer at the Second Affiliated Hospital of Soochow University between January 2016 and December 2022 were included. The skeletal muscle and fat area at the third lumbar vertebra were measured with preoperative CT measurement. MMFR was defined as the ratio of skeletal muscle area to total fat area, and low MMFR was defined as the 2 lowest tertiles (≤0.585). Univariate and multivariable analyses were conducted to assess the impact of MMFR on overall complications and survival outcomes. Kaplan-Meier survival curves and log-rank test were used to compare the overall survival between high MMFR and low MMFR groups. Results: A total of 885 patients were analyzed. Female sex, older age, high body mass index, sarcopenia, and high cancer stage were more likely to result in low MMFR. Complications, including intestinal fistula, chylous fistula and organ space surgical site infection were significantly higher in the low MMFR group. Low MMFR was an independent factor associated with overall complications (odds ratio, 1.940; 95% confidence interval [CI], 1.252-3.007; P < 0.01) and long-term survival (hazard ratio, 2.222; 95% CI, 1.443-3.425; P < 0.01). Furthermore, patients with high MMFR had a higher survival rate than patients with low MMFR (P < 0.01). Conclusion: Low MMFR is an independent factor that predicts worse overall survival and complications in patients with colon cancer.

8.
Foods ; 13(15)2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39123633

RESUMEN

The effect of wheat gluten (WG)/phenolic extracts (PE) coating on the storage qualities of salmon fillets was studied. Porphyra haitanensis, belonging to red algae, possesses abundant phenolic compounds. Films were prepared by incorporating phenolic extracts (0, 0.5%, 0.75%, and 1.0%, w/v) from Porphyra haitanensis to WG. The PE showed strong antioxidant activities by scavenging DPPH and ABTS radicals. The increased addition of PE to WG film significantly increased tensile strength compared to that of WG film, but reduced water vapor permeability. The quality of salmon fillet stored at 4 °C from 0 to 9 days was decreased due to the oxidation of lipid and protein. However, the increased addition of PE to WG significantly reduced pH, TVB-N, TBA, peroxide value, total sulfhydryl content, and carbonyl content of salmon fillet compared to control salmon fillet. In addition, the increased addition of PE to WG also significantly improved water holding capacity, hardness, chewiness, and springiness of salmon fillet during storage compared to those of control salmon fillet. Taken together, this study showed phenolic extracts from Porphyra haitanensis improved wheat gluten-based film properties and further enhanced the qualities of coated salmon fillet during storage.

9.
Water Res ; 263: 122178, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39096806

RESUMEN

Membrane-contamination during electrodialysis (ED) process is still a non-negligible challenge, while irreversible consumption and unsustainability have become the main bottlenecks limiting the improvement of anion exchange membranes (AEMs) anti-contamination activity. Here, we introduce a novel approach to design AEMs by chemically assembling 4-pyndinepropanol with bromomethylated poly(2,6-dimethyl-1,4-phenylene oxide) (BPPO) in an electrochromic-inspired process. Subsequently, the co-mingled TiO2@Ag nanosheet with the casting-solution were sprayed onto the surface of the substrate membrane to create a micrometer-thick interfacial layer. The addition of Ag nanoparticles (NPs) enhances the active sites of TiO2, resulting in stronger local surface plasmon resonance (LSPR) effects and reducing its energy band gap limitation (From 3.11 to 2.63 eV). Post-electrodialysis electrochromic AEMs incorporating TiO2@Ag exhibit synergistic enhancement of sunlight absorption, effectively suppressing photogenerated carrier binding and promoting migration. These resultant-membranes demonstrate significantly improved bacterial inhibition properties (42.0-fold increase for E. coli) and degradation activity (7.59-fold increase for rhodamine B) compared to pure TiO2 membranes. Importantly, they maintain photocatalytic activity without compromising salt-separation performance or stability, as the spraying process utilizes the same substrate materials. This approach to rational design and regulation of anti-contamination AEMs offers new insights into the collaborative synergy of color-changing and photocatalytic materials.


Asunto(s)
Membranas Artificiales , Plata , Titanio , Titanio/química , Plata/química , Catálisis , Luz , Escherichia coli/efectos de los fármacos , Diálisis , Aniones , Nanopartículas del Metal/química
10.
J Sci Food Agric ; 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39007208

RESUMEN

BACKGROUND: Apples are among the most nutritionally valuable fruits and have a history of use in traditional Chinese medicine. Triterpenoids, the primary bioactive compounds found in apples, demonstrate significant antitumor activity. RESULTS: Following enrichment and optimization, the total content of major triterpenoids in total triterpenoids from apple peels (ATT) reached 5.76 g kg-1. The growth of MDA-MB-231 xenograft tumors was significantly inhibited after treatment with ATT. Network pharmacology analysis conclusively identified a close association between the antitumor effect of ATT and the phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway. Experimental validation using MDA-MB-231 cells and a xenograft nude mouse model confirmed that ATT suppressed tumor cell proliferation effectively by modulating the PI3K-Akt signaling pathway, which was consistent with the findings from network pharmacology. The total triterpenoids from apple peels also induced cell apoptosis by mediating the PI3K-Akt signaling pathway. CONCLUSION: The total triterpenoids from apple peels can inhibit tumor cell proliferation and induce cell apoptosis effectively through the PI3K-Akt signaling pathway, suggesting that ATT holds promise as a prospective therapeutic agent for breast cancer treatment. © 2024 Society of Chemical Industry.

11.
IEEE J Biomed Health Inform ; 28(7): 4224-4237, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38954562

RESUMEN

The real-world Electronic Health Records (EHRs) present irregularities due to changes in the patient's health status, resulting in various time intervals between observations and different physiological variables examined at each observation point. There have been recent applications of Transformer-based models in the field of irregular time series. However, the full attention mechanism in Transformer overly focuses on distant information, ignoring the short-term correlations of the condition. Thereby, the model is not able to capture localized changes or short-term fluctuations in patients' conditions. Therefore, we propose a novel end-to-end Deformable Neighborhood Attention Transformer (DNA-T) for irregular medical time series. The DNA-T captures local features by dynamically adjusting the receptive field of attention and aggregating relevant deformable neighborhoods in irregular time series. Specifically, we design a Deformable Neighborhood Attention (DNA) module that enables the network to attend to relevant neighborhoods by drifting the receiving field of neighborhood attention. The DNA enhances the model's sensitivity to local information and representation of local features, thereby capturing the correlation of localized changes in patients' conditions. We conduct extensive experiments to validate the effectiveness of DNA-T, outperforming existing state-of-the-art methods in predicting the mortality risk of patients. Moreover, we visualize an example to validate the effectiveness of the proposed DNA.


Asunto(s)
Registros Electrónicos de Salud , Humanos , Algoritmos
12.
Front Public Health ; 12: 1357784, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39022424

RESUMEN

Background: Previous research has primarily examined the mental well-being of children from labor migrant families, yet there is a lack of understanding regarding the mental well-being of children from highly educated migrant backgrounds. This study investigated the social-emotional problems of 3-5-year-olds from highly educated migrant families residing in an urban area of China, as well as explored potential differences in demographic variables. Methods: A cross-sectional study was conducted in Qiantang District, Hangzhou, China, with 1,494 (53.3% boys) children selected via a convenient sampling method. The Ages & Stages Questionnaires: social-Emotional, Second Edition (ASQ:SE-2) was used to measure social-emotional problems. Results: The results showed that 23.6% of the children were at risk for social-emotional problems. More boys (26.7%) than girls (20.1%) had scores above the cut-off. Additionally, more children in the low socioeconomic status (29.9%) had scores above the cut-off than those in the high socioeconomic status (18.9%). There were three common issues among all age groups: "being more active than others," "excessive attachment to parents," and "being overly friendly with strangers. Conclusion: The social-emotional development of children from highly educated migrant families is a significant aspect that deserves recognition, contributing valuable insights to the existing literature on this topic.


Asunto(s)
Síntomas Afectivos , Salud Mental , Migrantes , Población Urbana , Preescolar , Femenino , Humanos , Masculino , China , Estudios Transversales , Pueblos del Este de Asia , Escolaridad , Encuestas y Cuestionarios , Migrantes/estadística & datos numéricos , Migrantes/psicología , Síntomas Afectivos/epidemiología
13.
Neuropathol Appl Neurobiol ; 50(4): e12996, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38982616

RESUMEN

AIM: Systemic amyloidosis is a condition in which misfolded amyloid fibrils are deposited within tissues. Amyloid myopathy is a rare manifestation of systemic amyloidosis. However, whether skeletal muscle involvement is underestimated and whether such deposition guarantees clinical and pathological myopathic features remain to be investigated. METHODS: We retrospectively reviewed patients with systemic amyloidosis, in whom skeletal muscle biopsies were performed at our centre between January 2018 and June 2023. In total, 28 patients with suspected systemic amyloidosis were included. Among these, 21 presented with cardiomyopathy but lacked myopathic symptoms. The clinical and pathological data of these patients were further analysed. The amyloid type was confirmed by immunohistochemistry. RESULTS: Twenty-eight patients with suspected systemic amyloidosis underwent muscle biopsy. Amyloid deposition in the skeletal muscle was confirmed in 24 patients, including 22 with light-chain amyloidosis (AL) and two with transthyretin amyloidosis (ATTR). Among the 24 patients, seven presented with muscle weakness and decreased muscle strength (Group 1, symptomatic myopathy), whereas the remaining 17 exhibited normal muscle strength (Group 2, asymptomatic myopathy). Group 1 included four patients with AL-λ, one with AL-κ and two with ATTR. Group 2 included 15 patients with AL-λ and two patients with AL-κ. In Group 1, six patients exhibited neuropathy, whereas only one patient in Group 2 presented with subclinical neuropathy on nerve conduction studies. Amyloid deposition in the interstitium was the most obvious change, observed in all 24 patients. Neuropathic changes, including denervation atrophy and muscle fibre grouping, were also common. Except for type 2 fibre atrophy, the other myopathic changes were mild and nonspecific. No sarcolemmal disruption was observed. Immunohistochemical analysis revealed marked positivity for MAC and MHC1 expression in the regions with amyloid deposits. Clinicopathological analysis revealed no significant differences in the extent of muscular amyloid deposition between the two groups. Nevertheless, patients in Group 1 displayed more pronounced neurogenic atrophy on skeletal muscle biopsies. CONCLUSIONS: Our study indicates that amyloid deposition in skeletal muscle is commonly observed but rarely causes symptomatic myopathy in systemic amyloidosis.


Asunto(s)
Músculo Esquelético , Enfermedades Musculares , Humanos , Masculino , Músculo Esquelético/patología , Músculo Esquelético/metabolismo , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Enfermedades Musculares/patología , Enfermedades Musculares/metabolismo , Amiloidosis/patología , Amiloidosis/complicaciones , Amiloidosis/metabolismo , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/patología , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/complicaciones , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/metabolismo , Anciano de 80 o más Años , Adulto , Biopsia
14.
Nat Commun ; 15(1): 5460, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937462

RESUMEN

Developing superporous hemostatic sponges with simultaneously enhanced permeability and mechanical properties remains challenging but highly desirable to achieve rapid hemostasis for non-compressible hemorrhage. Typical approaches to improve the permeability of hemostatic sponges by increasing porosity sacrifice mechanical properties and yield limited pore interconnectivity, thereby undermining the hemostatic efficacy and subsequent tissue regeneration. Herein, we propose a temperature-assisted secondary network compaction strategy following the phase separation-induced primary compaction to fabricate the superporous chitosan sponge with highly-interconnected porous structure, enhanced blood absorption rate and capacity, and fatigue resistance. The superporous chitosan sponge exhibits rapid shape recovery after absorbing blood and maintains sufficient pressure on wounds to build a robust physical barrier to greatly improve hemostatic efficiency. Furthermore, the superporous chitosan sponge outperforms commercial gauze, gelatin sponges, and chitosan powder by enhancing hemostatic efficiency, cell infiltration, vascular regeneration, and in-situ tissue regeneration in non-compressible organ injury models, respectively. We believe the proposed secondary network compaction strategy provides a simple yet effective method to fabricate superporous hemostatic sponges for diverse clinical applications.


Asunto(s)
Quitosano , Hemostasis , Hemostáticos , Permeabilidad , Animales , Porosidad , Quitosano/química , Hemostáticos/química , Hemostáticos/farmacología , Porcinos , Hemostasis/fisiología , Hemorragia/terapia , Masculino
15.
EMBO Rep ; 25(8): 3373-3405, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38943004

RESUMEN

Centrosomes are the canonical microtubule organizing centers (MTOCs) of most mammalian cells, including spermatocytes. Centrosomes comprise a centriole pair within a structurally ordered and dynamic pericentriolar matrix (PCM). Unlike in mitosis, where centrioles duplicate once per cycle, centrioles undergo two rounds of duplication during spermatogenesis. The first duplication is during early meiotic prophase I, and the second is during interkinesis. Using mouse mutants and chemical inhibition, we have blocked centriole duplication during spermatogenesis and determined that non-centrosomal MTOCs (ncMTOCs) can mediate chromosome segregation. This mechanism is different from the acentriolar MTOCs that form bipolar spindles in oocytes, which require PCM components, including gamma-tubulin and CEP192. From an in-depth analysis, we identified six microtubule-associated proteins, TPX2, KIF11, NuMA, and CAMSAP1-3, that localized to the non-centrosomal MTOC. These factors contribute to a mechanism that ensures bipolar MTOC formation and chromosome segregation during spermatogenesis when centriole duplication fails. However, despite the successful completion of meiosis and round spermatid formation, centriole inheritance and PLK4 function are required for normal spermiogenesis and flagella assembly, which are critical to ensure fertility.


Asunto(s)
Centriolos , Segregación Cromosómica , Proteínas Asociadas a Microtúbulos , Centro Organizador de los Microtúbulos , Espermatocitos , Espermatogénesis , Centriolos/metabolismo , Centriolos/genética , Animales , Masculino , Ratones , Espermatogénesis/genética , Espermatocitos/metabolismo , Centro Organizador de los Microtúbulos/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Asociadas a Microtúbulos/genética , Meiosis/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética
16.
Int J Nanomedicine ; 19: 5995-6014, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38895150

RESUMEN

Introduction: To improve the bioavailability of trans-resveratrol (trans-Res), it is commonly co-delivered with antioxidant bioactives using a complex synthetic intestinal targeted carrier, however, which makes practical application challenging. Methods: A nanogel (Ngel), as broad-spectrum autonomous ROS scavenger, was prepared using selenized thiolated sodium alginate (TSA-Se) and crosslinked with calcium lactate (CL) for loading trans-Res to obtain Ngel@Res, which maintained spherical morphology in the upper digestive tract but broke down in the lower digestive tract, resulting in trans-Res release. Results: Under protection of Ngel, trans-Res showed enhanced stability and broad-spectrum ROS scavenging activity. The synergistic mucoadhesion of Ngel prolonged the retention time of trans-Res in the intestine. Ngel and Ngel@Res increased the lifespan of Caenorhabditis elegans to 26.00 ± 2.17 and 26.00 ± 4.27 days by enhancing the activity of antioxidases, upregulating the expression of daf-16, sod-5 and skn-1, while downregulating the expression of daf-2 and age-1. Conclusion: This readily available, intestinal targeted selenized alginate-based nanogel effectively improves the bioactivity of trans-Res.


Asunto(s)
Alginatos , Caenorhabditis elegans , Nanogeles , Especies Reactivas de Oxígeno , Resveratrol , Animales , Caenorhabditis elegans/efectos de los fármacos , Resveratrol/farmacología , Resveratrol/química , Resveratrol/farmacocinética , Resveratrol/administración & dosificación , Especies Reactivas de Oxígeno/metabolismo , Alginatos/química , Alginatos/farmacología , Nanogeles/química , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/farmacocinética , Polietilenglicoles/química , Polietilenglicoles/farmacología , Polietileneimina/química , Polietileneimina/farmacología , Polietileneimina/farmacocinética , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/farmacocinética , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética
17.
Ultrason Sonochem ; 107: 106934, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38834001

RESUMEN

Herein, the effects of ultrasound-assisted L-histidine (L-His) on the physicochemical properties and conformation of soybean protein isolate (SPI) were investigated. Particle size, zeta potential, turbidity, and solubility were used to evaluate protein aggregation, and the relationship between structural and functional changes of the proteins was characterized using spectral analysis, surface hydrophobicity, emulsification, and antioxidant properties. After ultrasound-assisted L-His treatment, SPI exhibited a smaller particle size, higher solubility, and more homogeneous micromorphology owing to the decrease in alpha-helix content and subsequent increases in zeta potential and active sulfhydryl content. In addition, spectral analysis showed that L-His and SPI could form a complex, which changed the microenvironment of the amino acid residues in SPI, thus improving its emulsification and antioxidant properties. At the concentration of L-His was 0.3 % w/w, the nanocomplex had a smaller particle size (140.03 nm), higher ζ-potential (-23.63 mV), and higher emulsification stability (22.48 min).


Asunto(s)
Antioxidantes , Histidina , Tamaño de la Partícula , Proteínas de Soja , Histidina/química , Proteínas de Soja/química , Antioxidantes/química , Solubilidad , Ondas Ultrasónicas , Interacciones Hidrofóbicas e Hidrofílicas , Relación Estructura-Actividad
18.
Phytochemistry ; 225: 114191, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38901625

RESUMEN

Herein, 17 previously undescribed polyacetylenes and 9 known ones were isolated from Tridax procumbens L. Their structures were identified using spectroscopic techniques (NMR, UV, IR, MS and optical rotation), the modified Mosher method, electronic circular dichroism (ECD) data and ECD calculation. The cytotoxicity of polyacetylenes on six human tumour cell lines (K562, K562/ADR, AGS, MGC-803, SPC-A-1 and MDA-MB-231) was evaluated. (3S,10R)-tridaxin B (2a), (3S,10S)-tridaxin B (2b) and tridaxin F (8) demonstrated substantial cytotoxic effects against the K562 cell line, with half-maximal inhibitory concentration (IC50) values of 2.62, 14.43 and 17.91 µM, respectively. Cell and nucleus morphology assessments and Western blot analysis confirmed that the cytotoxicity of the three polyacetylenes on K562 cells was mediated through a dose-dependent apoptosis pathway. Furthermore, (3S,10R)-tridaxin A (1a) and tridaxin G (9) exhibited considerable inhibitory effects on lipopolysaccharide-stimulated nitric oxide production in RAW 264.7 macrophages, with IC50 values of 15.92 and 20.35 µM, respectively. Further investigations revealed that 9 exerted anti-inflammatory activities by impeding the nuclear translocation of NF-κB and down-regulating the expression of pro-inflammatory factors, including those of iNOS, COX-2, IL-1ß and IL-6, in a concentration-dependent manner. The study provides evidence that polyacetylenes from T. procumbens may serve as a potential source of anti-tumour or anti-inflammatory agents for treating related diseases.


Asunto(s)
Antiinflamatorios , Antineoplásicos Fitogénicos , Poliinos , Humanos , Poliinos/farmacología , Poliinos/química , Poliinos/aislamiento & purificación , Ratones , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Apoptosis/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Células RAW 264.7 , Estructura Molecular , Relación Dosis-Respuesta a Droga , Lipopolisacáridos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Asteraceae/química , Células K562 , Relación Estructura-Actividad , Proliferación Celular/efectos de los fármacos , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , FN-kappa B/metabolismo , FN-kappa B/antagonistas & inhibidores , Línea Celular Tumoral
19.
Toxics ; 12(6)2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38922073

RESUMEN

Ambient particulate matter (PM) pollution is a leading environmental health threat worldwide. PM with an aerodynamic diameter ≤ 1.0 µm, also known as PM1, has been implicated in the morbidity and mortality of several cardiorespiratory and cerebrovascular diseases. However, previous studies have mostly focused on analyzing fine PM (PM2.5) associated with disease metrics, such as emergency department visits and mortality, rather than ultrafine PM, including PM1. This study aimed to evaluate the association between short-term PM1 exposure and hospital admissions (HAs) for all-cause diseases, chronic obstructive pulmonary disease (COPD), and respiratory infections (RIs), as well as the associated expenditures, using Beijing as a case study. Here, based on air pollution and hospital admission data in Beijing from 2015 to 2017, we performed a time-series analysis and meta-analysis. It was found that a 10 µg/m3 increase in the PM1 concentration significantly increased all-cause disease HAs by 0.07% (95% Confidence Interval (CI): [0, 0.14%]) in Beijing between 2015 and 2017, while the COPD and RI-related HAs were not significantly associated with short-term PM1 exposure. Meanwhile, we estimated the attributable number of HAs and hospital expenditures related to all-cause diseases. This study revealed that an average of 6644 (95% CI: [351, 12,917]) cases of HAs were attributable to ambient PM1, which was estimated to be associated with a 106 million CNY increase in hospital expenditure annually (95% CI: [5.6, 207]), accounting for 0.32% (95% CI: [0.02, 0.62%]) of the annual total expenses. The findings reported here highlight the underlying impact of ambient PM pollution on health risks and economic burden to society and indicate the need for further policy actions on public health.

20.
Int J Biol Macromol ; 274(Pt 1): 133120, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38876244

RESUMEN

The utilization of basic fibroblast growth factor (bFGF) in the development of tissue-engineered scaffolds is both challenging and imperative. In our pursuit of creating a scaffold that aligns with the natural healing process, we initially fabricated chitosan-bFGF nanoparticles (CS-bFGF NPs) through electrostatic spraying. Subsequently, polylactic acid (PLA) fiber was prepared using electrospinning technique, and the CS-bFGF NPs were uniformly embedded within the pores of porous PLA fibers. Scanning electron micrographs illustrate the smooth surface of the nanoparticles, showing a porous structure intricately attached to PLA fibers. Fourier-transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD) analyses provided conclusive evidence that the CS-bFGF NPs were uniformly distributed throughout the porous PLA fibers, forming a robust physical bond through electrostatic adsorption. The resultant scaffolds exhibited commendable mechanical properties and hydrophilicity, facilitating a sustained-release for 72 h. Furthermore, the biocompatibility and degradation performance of the scaffolds were substantiated by monitoring conductivity and pH changes in pure water over different time intervals, complemented by scanning electron microscopy (SEM) observations. Cell experiments confirmed the cytocompatibility of the scaffolds. In animal studies, the group treated with 16 % NPs/Scaffold demonstrated the highest epidermal reconstruction rate. In summary, our developed materials present a promising candidate for serving as a tissue engineering scaffold, showcasing exceptional biocompatibility, sustained-release characteristics, and substantial potential for promoting epidermal regeneration.


Asunto(s)
Quitosano , Preparaciones de Acción Retardada , Nanopartículas , Poliésteres , Albúmina Sérica Bovina , Ingeniería de Tejidos , Andamios del Tejido , Quitosano/química , Poliésteres/química , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Nanopartículas/química , Animales , Albúmina Sérica Bovina/química , Porosidad , Materiales Biocompatibles/química , Bovinos
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