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1.
Int J Biol Macromol ; : 136153, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39362438

RESUMEN

Polysaccharides serve as a source of energy for organisms and play a crucial role in various life activities, exhibiting a wide array of biological functions. To develop bioactive polysaccharides for combating cancer, PGP40-2B, a homogeneous polysaccharide with a molecular weight of 7.05 × 103 g/mol, has been isolated from Platycodon grandiflorum, which is a traditional medicinal and edible plant with multiple functions. PGP40-2B was found to mainly formed from several fragments including →2)-α-l-Araf-(1→, →5)-α-l-Araf-(1→, →3,4)-α-l-Rhap-(1→, →4)-α-d-GalpA-(1→, →6)-α-d-Glcp-(1→, and α-d-Galp-(1→. In addition to the structural characteristics characterized by various techniques, PGP40-2B was biologically assessed using zebrafish models and was found to exhibit in vivo antitumor effects. Subsequent mechanism studies suggested that the antitumor activity in vivo of PGP40-2B was not caused by cytotoxic mechanisms but was related to its targeting of vascular endothelial growth factor (VEGF) and programmed cell death protein 1 (PD-1) to inhibit angiogenesis and activate immunity.

2.
Int J Biol Macromol ; 281(Pt 3): 136506, 2024 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-39395520

RESUMEN

Glutathione S-transferases (GSTs) are proteases with multiple physiological functions and play an important role in plant responses to abiotic stresses. Nevertheless, there is a paucity of systematic research on GST genes in Prunus genus. Here, 330 GST genes in four Prunus species were identified for the first time and classified into eight subgroups based on protein sequence and conserved structure, among which Tau subfamily genes had the largest number. The amino acid lengths of GST-encoded proteins in the four species ranged from 66 to 1152 aa, most of which were soluble proteins and located in the cytoplasm and chloroplasts. The GST family was propelled by tandem duplications, yet robust purifying selection constrained its divergence. Conserved motif and domain analysis revealed that the majority of PmGSTs exhibited a highly conserved GST-N structure. The expression pattern of PmGSTs exhibited tissue specificity and spatiotemporal specificity. qRT-PCR validated the transcriptome results and 11 genes were differentially expressed in varieties with different flower and stem colors. In addition, we discovered an anthocyanin-related gene PmGSTF2, which can effectively restore the anthocyanin and proanthocyanidin deficiency-related phenotypes of the Arabidopsis tt19 mutant. Recombinant PmGSTF2 enhanced the water solubility of cyanidin and cyanidin-3-O-glucoside in vitro. Moreover, PmMYBa1 could directly bind to the promoter of PmGSTF2 and activate its expression. The findings revealed that GSTs were preserved in Prunus species and that PmGSTF2 was critical in regulating anthocyanin accumulation.

4.
Aesthetic Plast Surg ; 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39218835

RESUMEN

BACKGROUND: Botulinum toxin type A (BTXA) can improve wound healing and reduce scar formation; however, the exact dose required to prevent postoperative scarring across various anatomical sites remains unclear. This study aimed to investigate the effectiveness and optimal concentrations of BTXA for preventing postoperative scarring across various common surgical sites throughout the body. METHODS: In this prospective randomized controlled trial, 46 patients with benign skin tumors received injections of 1, 2.5, or 5 U/0.1 mL of BTXA or 0.9% saline immediately following surgical tumor excision on both sides of the incisions. Follow-ups were conducted at 7 days, 15 days, and 1, 3, and 6 months postoperatively. Patient-reported adverse events and standardized digital photographs were collected. Scar formation was assessed using the modified Stony Brook Scar Evaluation Scale (mSBSES). RESULTS: All 46 patients completed the trial without severe complications. The mSBSES scores were higher in the experimental groups at all follow-ups. The 5 U/0.1 mL BTXA dose group demonstrated optimal scar prevention at all high-risk sites for scar hyperplasia. No significant difference was observed between the 2.5 U/0.1 mL and 5 U/0.1 mL doses for intermediate-risk sites, while 1 U/0.1 mL dose was sufficient for low-risk sites. Overall, 86.5% of patients were satisfied with their treatments, with 16.3% being very satisfied. CONCLUSIONS: Early postoperative BTXA injection can reduce or prevent hypertrophic scarring, with optimal doses ranging from 1 to 5 U/0.1 mL depending on the surgical site, supporting broader clinical application of BTXA. The effectiveness of different concentrations of botulinum toxin type A (BTXA) in preventing postoperative scarring was compared, expanding the scope of previous research, which focused only on the head, face, and neck regions, to include the trunk and extremity areas. Different optimal injection strategies were determined based on different surgical sites and their risks of developing hypertrophic scars. The study demonstrates that BTXA not only reduces scar formation but also enhances patient satisfaction and reduces postoperative itching and pain, contributing to overall better postoperative outcomes. By establishing the efficacy and optimal dosing of BTXA for various surgical sites, this research supports the potential for broader clinical application of BTXA in aesthetic and reconstructive surgeries. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

5.
Int J Mol Sci ; 25(17)2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39273581

RESUMEN

Cancer continues to be a major global health issue, ranking among the top causes of death worldwide. To develop novel antitumor agents, this study focused on the synthesis of a series of 21 novel furanopyridinone derivatives through structural modifications and functional enhancements. The in vitro anti-tumor activities of these compounds were investigated through the cytotoxicity against KYSE70 and KYSE150 and led to the identification of compound 4c as the most potent compound. At a concentration of 20 µg/mL, compound 4c demonstrated a remarkable 99% inhibition of KYSE70 and KYSE150 cell growth after 48 h. IC50 was 0.655 µg/mL after 24 h. Additionally, potential anti-tumor cellular mechanisms were explored through molecular docking, which was used to predict the binding mode of 4c with METAP2 and EGFR, suggesting that the C=O part of the pyridone moiety likely played a crucial role in binding. This study provided valuable insights and guidance for the development of novel anticancer drugs with novel structural scaffolds.


Asunto(s)
Antineoplásicos , Proliferación Celular , Neoplasias Esofágicas , Simulación del Acoplamiento Molecular , Piridonas , Humanos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Piridonas/farmacología , Piridonas/química , Piridonas/síntesis química , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/metabolismo , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Ensayos de Selección de Medicamentos Antitumorales , Apoptosis/efectos de los fármacos
6.
Ann Plast Surg ; 93(4): 434-442, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39331743

RESUMEN

BACKGROUND: Scars disrupt the normal structure and function of the skin. The primary goal of plastic surgery is to prevent and reduce scarring. Therefore, we aimed to establish a comparison scheme between normal skin (NS) tissues of different ages and locations; hypertrophic scars (HTS) of different ages, locations, and maturities; and NS and HTS tissues to provide evidence on scar severity for improving treatment evaluation. METHODS: Various methods including histology, immunohistochemistry, and immunofluorescence were employed to compare the general appearance, macrophage infiltration, fibroblast activity, degree of angiogenesis, and collagen fiber type and arrangement in human-sourced NS and HTS tissues of different ages, locations, and maturities in seven patients (three with NS and four with HTS) from the Department of Burn and Plastic Surgery of the Shandong Provincial Hospital from January 2019 to December 2020. RESULTS: The thicknesses of the epidermis and dermis of NS tissues varied with age and location. The epidermis of the upper arms, face, and upper eyelids of NS tissues sequentially thickened, whereas the dermis was sequentially thinner. Several glandular structures were identified in the upper eyelids but rarely in the face and upper arms. Histological changes in HTS tissue of different ages, locations, and maturity occur as scar formation time is prolonged, accompanied by increased CD86 levels and fibrosis. As the scar matured, connexin and VEGFR2 expression decreased, indicating reduced inflammation, fibroblast activity, and angiogenesis. The comparison between NS and HTS tissue also revealed significant differences; the positive expression of VEGFR2 and total collagen in HTS tissue was higher than that in NS tissue. CONCLUSIONS: We discovered significant differences among NS, HTS, and NS and HTS tissues of different ages, locations, and maturities. Further, this study may provide a basis for clarifying the treatment effect of different methods for HTS compared with those for NS, efficiently individualizing patients' treatment plans and ultimately shortening the scar treatment process.


Asunto(s)
Cicatriz Hipertrófica , Piel , Humanos , Cicatriz Hipertrófica/patología , Femenino , Masculino , Adulto , Piel/patología , Piel/metabolismo , Adolescente , Adulto Joven , Factores de Edad , Niño , Persona de Mediana Edad
7.
BMC Infect Dis ; 24(1): 991, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39289630

RESUMEN

BACKGROUND: To estimate vaccine effectiveness(VE) against COVID-19-related hospitalization for inactivated vaccines during the Omicron BF.7-predominant epidemic wave in Beijing, China. METHODS: We recruited a cohort in Beijing on 17 and 18 December 2022, collected status of vaccination and COVID-19-related hospitalization since 1 November 2022 and prospectively followed until 9 January 2023. A Poisson regression model was used to estimate the VE. RESULTS: 16(1.15%) COVID-19-related hospitalizations were reported in 1391 unvaccinated participants; 7(0.25%) in 2765 participants with two doses, resulting in a VE of 70.89%(95% confidence interval[CI] 26.25 to 87.73); 32(0.27%) in 11,846 participants with three doses, with a VE of 65.25%(95% CI 32.24 to 81.83). The VE of three doses remained above 64% at 1 year or more since the last dose. Elderly people aged ≥ 60 years had the highest hospitalization incidence(0.66%), VE for two doses was 74.11%(95%CI: - 18.42 to 94.34) and VE for three doses was 80.98%(95%CI:52.83 to 92.33). We estimated that vaccination had averted 65,007(95%CI: 12,817 to 97,757) COVID-19-related hospitalizations among people aged ≥ 60 years during the BF.7-predominant period in Beijing. CONCLUSION: Inactivated COVID-19 vaccines were effective against COVID-19-related hospitalization, especially for the elderly population who have increased risk of severe disease owing to SARS-CoV-2 infection.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Hospitalización , SARS-CoV-2 , Eficacia de las Vacunas , Vacunas de Productos Inactivados , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/inmunología , Persona de Mediana Edad , Hospitalización/estadística & datos numéricos , Masculino , Femenino , Adulto , Anciano , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/inmunología , SARS-CoV-2/inmunología , Beijing/epidemiología , Adulto Joven , Estudios de Cohortes , Adolescente , Vacunación/estadística & datos numéricos , Estudios Prospectivos , China/epidemiología , Niño , Anciano de 80 o más Años
8.
Int J Biol Macromol ; 279(Pt 4): 135386, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39245122

RESUMEN

Because of eco-friendliness, biodegradability and ease of modification, cellulose is deemed as alternative to unrenewable petroleum resources. Nonetheless, it is more indispensable to exploit corn cob cellulose produced from agricultural waste residue as supportive materials in green catalysis. In this study, a new magnetically benzimidazole functionalized cellulose/Fe3O4 derived from corn cob cellulose as a stabilizer agent (Fe3O4@CL-NHC) was prepared, and palladium was immobilized on this stabilizer (Fe3O4@CL-NHC-Pd). The catalyst was fully characterized by different techniques including TEM, SEM, and XPS analyses, etc. The abundant hydroxyl groups of cellulose provided uniform dispersion and high stability of palladium, while Fe3O4 as a support offered simple magnetic separation. High efficiency (up to 99 %) was demonstrated by this biocatalyst under green conditions in relatively short reaction times towards Suzuki reactions. Due to collaborative interactions of N-heterocyclic carbene and hydroxyl groups with palladium, the synthesized complex prevented metal leaching effectively (<1 %). Moreover, the magnetic property of this catalyst (43.0 emu g-1) provides facile recovery of this composite from the reaction mixture with great ease for several times, which overcomes issues of complicated work-up separation. This work offers a promising avenue to enriching the application of biopolymer from agricultural residue in the potential organic transformations.


Asunto(s)
Celulosa , Metano , Paladio , Zea mays , Paladio/química , Catálisis , Zea mays/química , Celulosa/química , Metano/química , Metano/análogos & derivados , Agricultura , Compuestos Heterocíclicos/química , Fenómenos Magnéticos
10.
Nat Commun ; 15(1): 7455, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39198451

RESUMEN

Increased fatty acid synthesis benefits glioblastoma malignancy. However, the coordinated regulation of cytosolic acetyl-CoA production, the exclusive substrate for fatty acid synthesis, remains unclear. Here, we show that proto-oncogene tyrosine kinase c-SRC is activated in glioblastoma and remodels cytosolic acetyl-CoA production for fatty acid synthesis. Firstly, acetate is an important substrate for fatty acid synthesis in glioblastoma. c-SRC phosphorylates acetyl-CoA synthetase ACSS2 at Tyr530 and Tyr562 to stimulate the conversion of acetate to acetyl-CoA in cytosol. Secondly, c-SRC inhibits citrate-derived acetyl-CoA synthesis by phosphorylating ATP-citrate lyase ACLY at Tyr682. ACLY phosphorylation shunts citrate to IDH1-catalyzed NADPH production to provide reducing equivalent for fatty acid synthesis. The c-SRC-unresponsive double-mutation of ACSS2 and ACLY significantly reduces fatty acid synthesis and hampers glioblastoma progression. In conclusion, this remodeling fulfills the dual needs of glioblastoma cells for both acetyl-CoA and NADPH in fatty acid synthesis and provides evidence for glioma treatment by c-SRC inhibition.


Asunto(s)
Acetilcoenzima A , Ácidos Grasos , Glioblastoma , Proto-Oncogenes Mas , Glioblastoma/metabolismo , Glioblastoma/genética , Glioblastoma/patología , Humanos , Ácidos Grasos/metabolismo , Ácidos Grasos/biosíntesis , Línea Celular Tumoral , Fosforilación , Acetilcoenzima A/metabolismo , Animales , Proteína Tirosina Quinasa CSK/metabolismo , Proteína Tirosina Quinasa CSK/genética , Familia-src Quinasas/metabolismo , Familia-src Quinasas/genética , Progresión de la Enfermedad , Ratones , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , NADP/metabolismo , Ratones Desnudos , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/metabolismo
11.
J Immunother Cancer ; 12(7)2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39089739

RESUMEN

BACKGROUND: Immune-related adverse events (irAEs), characterized by targeted inflammation, occur in up to 60% of patients with melanoma treated with immune checkpoint inhibitors (ICIs). Evidence proved that the baseline peripheral blood profiles of patients at risk for severe irAEs development paralleled clinical autoimmunity. Interleukin (IL)-23 blockade with risankizumab is recommended for cases that are suffering from autoimmune disease, such as autoimmune colitis. However, currently, the role of IL-23 in irAEs onset and severity remains poorly understood. METHODS: The pro-inflammatory cytokines most associated with severe irAEs onset were identified by retrospective analysis based on GSE186143 data set. To investigate the efficacy of prophylactic IL-23 blockade administration to prevent irAEs, refer to a previous study, we constructed two irAEs murine models, including dextran sulfate sodium salt (DSS)-induced colitis murine model and a combined-ICIs-induced irAEs murine model. To further explore the applicability of our findings, murine models with graft-versus-host disease were established, in which Rag2-/-Il2rg-/- mice were transferred with human peripheral blood mononuclear cells and received combined cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and programmed cell death protein-1 (PD-1) treatment. Human melanoma cells were xenografted into these mice concomitantly. RESULTS: Here we show that IL-23 was upregulated in the serum of patients suffering from irAEs after dual anti-CTLA-4 and anti-PD-1 treatment, and increased as a function of irAEs severity. Additionally, Augmented CD4+ Tems may preferentially underlie irAEs onset. Treating mice with anti-mouse IL-23 antibody concomitantly with combined CTLA-4 and PD-1 immunotherapy ameliorates colitis and, in addition, preserves antitumor efficacy. Moreover, in xenografted murine models with irAEs, prophylactic blockade of human IL-23 using clinically available IL-23 inhibitor (risankizumab) ameliorated colitis, hepatitis and lung inflammation, and moreover, immunotherapeutic control of tumors was retained. Finally, we also provided a novel machine learning-based computational framework based on two blood-based features-IL-23 and CD4+ Tems-that may have predictive potential for severe irAEs and ICIs response. CONCLUSIONS: Our study not only provides clinically feasible strategies to dissociate efficacy and toxicity in the use of combined ICIs for cancer immunotherapy, but also develops a blood-based biomarker that makes it possible to achieve a straightforward and non-invasive, detection assay for early prediction of irAEs onset.


Asunto(s)
Antígeno CTLA-4 , Interleucina-23 , Animales , Ratones , Humanos , Antígeno CTLA-4/antagonistas & inhibidores , Interleucina-23/antagonistas & inhibidores , Interleucina-23/metabolismo , Femenino , Inmunoterapia/métodos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Modelos Animales de Enfermedad , Melanoma/tratamiento farmacológico , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Masculino , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Estudios Retrospectivos
12.
Nat Commun ; 15(1): 6321, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39060269

RESUMEN

Spinal cord injury (SCI) leads to fibrotic scar formation at the lesion site, yet the heterogeneity of fibrotic scar remains elusive. Here we show the heterogeneity in distribution, origin, and function of fibroblasts within fibrotic scars after SCI in mice and female monkeys. Utilizing lineage tracing and single-cell RNA sequencing (scRNA-seq), we found that perivascular fibroblasts (PFs), and meningeal fibroblasts (MFs), rather than pericytes/vascular smooth cells (vSMCs), primarily contribute to fibrotic scar in both transection and crush SCI. Crabp2 + /Emb+ fibroblasts (CE-F) derived from meninges primarily localize in the central region of fibrotic scars, demonstrating enhanced cholesterol synthesis and secretion of type I collagen and fibronectin. In contrast, perivascular/pial Lama1 + /Lama2+ fibroblasts (LA-F) are predominantly found at the periphery of the lesion, expressing laminin and type IV collagen and functionally involved in angiogenesis and lipid transport. These findings may provide a comprehensive understanding for remodeling heterogeneous fibrotic scars after SCI.


Asunto(s)
Cicatriz , Fibroblastos , Fibrosis , Laminina , Traumatismos de la Médula Espinal , Animales , Traumatismos de la Médula Espinal/patología , Traumatismos de la Médula Espinal/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patología , Cicatriz/patología , Cicatriz/metabolismo , Ratones , Femenino , Laminina/metabolismo , Meninges/patología , Meninges/metabolismo , Fibronectinas/metabolismo , Modelos Animales de Enfermedad , Colágeno Tipo I/metabolismo , Ratones Endogámicos C57BL , Pericitos/metabolismo , Pericitos/patología , Colágeno Tipo IV/metabolismo , Colesterol/metabolismo
13.
Theriogenology ; 226: 308-318, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38959841

RESUMEN

Dielectric barrier discharge (DBD) plasma regulates the levels of reactive oxygen species (ROS), which are critical for sperm quality. MicroRNAs (miRNAs) are non-coding single-stranded RNA molecules encoded by endogenous genes, which regulate post-transcriptional gene expression in animals. At present, it is unknown whether DBD plasma can regulate sperm ROS levels through miRNAs. To further understand the regulatory mechanism of DBD plasma on sperm ROS levels, miRNAs in fresh boar spermatozoa were detected using Illumina deep sequencing technology. We found that 25 known miRNAs and 50 novel miRNAs were significantly upregulated, and 14 known miRNAs and 74 novel miRNAs were significantly downregulated in DBD plasma-treated spermatozoa. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that target genes of differentially expressed miRNAs were involved in many activities and pathways associated with antioxidants. We verified that DBD plasma significantly increased boar sperm quality and reduced ROS levels. These results suggest that DBD plasma can improve sperm quality by regulating ROS levels via miRNAs. Our findings provide a potential strategy to improve sperm quality through miRNA-targeted regulation of ROS, which helps to increase male reproduction and protect cryopreserved semen in clinical practice.


Asunto(s)
MicroARNs , Especies Reactivas de Oxígeno , Espermatozoides , Animales , Masculino , MicroARNs/metabolismo , MicroARNs/genética , Espermatozoides/fisiología , Espermatozoides/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Porcinos/fisiología , Análisis de Semen/veterinaria , Gases em Plasma/farmacología , Regulación de la Expresión Génica/fisiología , Preservación de Semen/veterinaria
14.
ACS Appl Mater Interfaces ; 16(30): 39631-39641, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39022811

RESUMEN

In response to growing concerns about public safety and environmental conservation, it is essential to develop a precise identification method for trace explosives. To improve the stability and detection sensitivity of perovskite quantum dots (PQDs) and address the issue of low porosity in traditional polymer-based photonic crystals (PhCs), this study proposed a PQD photoluminescence (PL) enhancement strategy based on the slow light effect of ZIF-8 PhCs for highly sensitive, selective, and convenient detection of 2,4,6-trinitrophenol (TNP). The slow light effect at the photonic band gap edge is the basis of amplifying the PL signal. PhCs were fabricated by the evaporation-induced self-assembly method. The diffraction wavelength overlapping the whole visible region was designed to match the emission wavelength of PQDs. Results showed that PhCs matching the PBG edge with PQDs' emission peak amplified the PL signal 11.3 times, significantly improving sensitivity for trace TNP detection with a limit as low as 2.52 nM. Moreover, there was a 13.3-fold enhancement of PQDs' fluorescence lifetime when the emission wavelength fell in the PBG range. The hydrophobic surface of ZIF-8 PhCs enhanced the PQDs' stability and moisture resistance. Furthermore, the selective quenching mechanism of TNP by the sensor was photoinduced electron transfer (PET) verified by DFT calculations and time-resolved PL decay dynamics measurements. This study demonstrated great potential for manipulating light emission enhancement by PhCs in developing efficient fluorescent sensors for trace environmental pollutant detection.

15.
Light Sci Appl ; 13(1): 151, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956018

RESUMEN

Spin glass theory, as a paradigm for describing disordered magnetic systems, constitutes a prominent subject of study within statistical physics. Replica symmetry breaking (RSB), as one of the pivotal concepts for the understanding of spin glass theory, means that under identical conditions, disordered systems can yield distinct states with nontrivial correlations. Random fiber laser (RFL) based on Rayleigh scattering (RS) is a complex disordered system, owing to the disorder and stochasticity of RS. In this work, for the first time, a precise theoretical model is elaborated for studying the photonic phase transition via the platform of RS-based RFL, in which we clearly reveal that, apart from the pump power, the photon phase variation in RFL is also an analogy to the temperature term in spin-glass phase transition, leading to a novel insight into the intrinsic mechanisms of photonic phase transition. In addition, based on this model and real-time high-fidelity detection spectral evolution, we theoretically predict and experimentally observe the mode-asymmetric characteristics of photonic phase transition in RS-based RFL. This finding contributes to a deeper understanding of the photonic RSB regime and the dynamics of RS-based RFL.

16.
Front Immunol ; 15: 1380229, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38911867

RESUMEN

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


Asunto(s)
Neoplasias del Colon , Diterpenos , Micelas , Polisacáridos , Animales , Neoplasias del Colon/tratamiento farmacológico , Diterpenos/química , Diterpenos/farmacología , Diterpenos/administración & dosificación , Humanos , Ratones , Línea Celular Tumoral , Polisacáridos/química , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Sistemas de Liberación de Medicamentos , Ensayos Antitumor por Modelo de Xenoinjerto , Portadores de Fármacos/química , Nanopartículas/química , Sistema de Administración de Fármacos con Nanopartículas/química , Ratones Desnudos , Ratones Endogámicos BALB C
17.
Nat Commun ; 15(1): 5238, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38898098

RESUMEN

While sanguinarine has gained recognition for antimicrobial and antineoplastic activities, its complex conjugated structure and low abundance in plants impede broad applications. Here, we demonstrate the complete biosynthesis of sanguinarine and halogenated derivatives using highly engineered yeast strains. To overcome sanguinarine cytotoxicity, we establish a splicing intein-mediated temperature-responsive gene expression system (SIMTeGES), a simple strategy that decouples cell growth from product synthesis without sacrificing protein activity. To debottleneck sanguinarine biosynthesis, we identify two reticuline oxidases and facilitated functional expression of flavoproteins and cytochrome P450 enzymes via protein molecular engineering. After comprehensive metabolic engineering, we report the production of sanguinarine at a titer of 448.64 mg L-1. Additionally, our engineered strain enables the biosynthesis of fluorinated sanguinarine, showcasing the biotransformation of halogenated derivatives through more than 15 biocatalytic steps. This work serves as a blueprint for utilizing yeast as a scalable platform for biomanufacturing diverse benzylisoquinoline alkaloids and derivatives.


Asunto(s)
Benzofenantridinas , Isoquinolinas , Ingeniería Metabólica , Saccharomyces cerevisiae , Temperatura , Isoquinolinas/metabolismo , Isoquinolinas/química , Benzofenantridinas/metabolismo , Benzofenantridinas/biosíntesis , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Ingeniería Metabólica/métodos , Halogenación , Sistema Enzimático del Citocromo P-450/metabolismo , Sistema Enzimático del Citocromo P-450/genética
18.
Foods ; 13(11)2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38891011

RESUMEN

The fermentation process of Chinese Baijiu's fermented grains involves the intricate succession and metabolism of microbial communities, collectively shaping the Baijiu's quality. Understanding the composition and succession of these living microbial communities within fermented grains is crucial for comprehending fermentation and flavor formation mechanisms. However, conducting high-throughput analysis of living microbial communities within the complex microbial system of fermented grains poses significant challenges. Thus, this study addressed this challenge by devising a high-throughput analysis framework using light-flavor Baijiu as a model. This framework combined propidium monoazide (PMA) pretreatment technology with amplicon sequencing techniques. Optimal PMA treatment parameters, including a concentration of 50 µM and incubation in darkness for 5 min followed by an exposure incubation period of 5 min, were identified. Utilizing this protocol, viable microorganism biomass ranging from 8.71 × 106 to 1.47 × 108 copies/µL was successfully detected in fermented grain samples. Subsequent amplicon sequencing analysis revealed distinct microbial community structures between untreated and PMA-treated groups, with notable differences in relative abundance compositions, particularly in dominant species such as Lactobacillus, Bacillus, Pediococcus, Saccharomycopsis, Issatchenkia and Pichia, as identified by LEfSe analysis. The results of this study confirmed the efficacy of PMA-amplicon sequencing technology for analyzing living microbial communities in fermented grains and furnished a methodological framework for investigating living microbial communities in diverse traditional fermented foods. This technical framework holds considerable significance for advancing our understanding of the fermentation mechanisms intrinsic to traditional fermented foods.

19.
J Cancer ; 15(11): 3381-3393, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38817872

RESUMEN

The prognostic roles of apoptosis-related genes (ARGs) in lung adenocarcinoma (LUAD) have not been fully elucidated. In this study, differentially expressed genes (DEGs) associated with apoptosis and the hub genes were further identified. The prognostic values of the ARGs were evaluated using the LASSO Cox regression method. Prognostic values were determined using Kaplan-Meier (K-M) curves and receiver operating characteristic (ROC) curves in the TCGA and GEO datasets. The correlations, mutation data, and protein expression of the 10 ARGs predictive models were also analyzed. We identified 130 differentially expressed ARGs. DEGs were used to split LUAD cases into two subtypes whose overall survival (OS) were significantly different (P = 0.025). We developed a novel 10-gene signature using LASSO Cox regression. In both TCGA and GEO datasets, the results of the K-M curve and log-rank test showed significant difference in the survival rate of patients in the high-risk group and low-risk group (P < 0.0001). According to the GO and KEGG analyses, ARGs were enriched in cancer-related terms. In both cohorts, the immune status of the high-risk group was significantly lower than that of the low-risk group. Based on the differential expression of the ARGs, we established a new risk model to predict the prognosis of patients with LUAD.

20.
Nanomaterials (Basel) ; 14(9)2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38727391

RESUMEN

Nanomaterials, with unique physical, chemical, and biocompatible properties, have attracted significant attention as an emerging active platform in cancer diagnosis and treatment. Amongst them, metal-organic framework (MOF) nanostructures are particularly promising as a nanomedicine due to their exceptional surface functionalities, adsorption properties, and organo-inorganic hybrid characteristics. Furthermore, when bioactive substances are integrated into the structure of MOFs, these materials can be used as anti-tumor agents with superior performance compared to traditional nanomaterials. In this review, we highlight the most recent advances in MOFs-based materials for tumor therapy, including their application in cancer treatment and the underlying mechanisms.

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