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1.
Food Chem ; 462: 141011, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-39226643

RESUMEN

Chlorogenic acid (CGA) is a well-known plant secondary metabolite exhibiting multiple physiological functions. The present study focused on screening for synergistic antibacterial combinations containing CGA. The combination of CGA and p-coumaric acid (pCA) exhibited remarkably enhanced antibacterial activity compared to that when administering the treatment only. Scanning electron microscopy revealed that a low-dose combination treatment could disrupt the Shigella dysenteriae cell membrane. A comprehensive analysis using nucleic acid and protein leakage assay, conductivity measurements, and biofilm formation inhibition experiments revealed that co-treatment increased the cell permeability and inhibited the biofilm formation substantially. Further, the polyacrylamide protein- and agarose gel-electrophoresis indicated that the proteins and DNA genome of Shigella dysenteriae severely degraded. Finally, the synergistic bactericidal effect was established for fresh-cut tomato preservation. This study demonstrates the remarkable potential of strategically selecting antibacterial agents with maximum synergistic effect and minimum dosage exhibiting excellent antibacterial activity in food preservation.


Asunto(s)
Antibacterianos , Ácido Clorogénico , Ácidos Cumáricos , Sinergismo Farmacológico , Shigella dysenteriae , Antibacterianos/farmacología , Antibacterianos/química , Ácidos Cumáricos/farmacología , Ácidos Cumáricos/química , Ácido Clorogénico/farmacología , Ácido Clorogénico/química , Shigella dysenteriae/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Biopelículas/efectos de los fármacos , Propionatos/farmacología , Solanum lycopersicum/química , Solanum lycopersicum/microbiología , Conservación de Alimentos/métodos
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 324: 124981, 2025 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-39154405

RESUMEN

The bimetallic nanostructure of Au and Ag can integrate two distinct properties into a novel substrate compared to single metal nanostructures. This work presents a rapid and sensitive surface-enhanced Raman scattering (SERS) substrate for detecting illegal food additives and dyes of crystal violet (CV) and alkali blue 6B (AB 6B). Au-Ag alloy nanoparticles/Ag nanowires (Au-Ag ANPs/Ag NWs) were prepared by solid-state ionics method and vacuum thermal evaporation method at 5µA direct current electric field (DCEF), the molar ratio of Au to Ag was 1:18.34. Many 40 nm-140 nm nanoparticles regularly existed on the surface of Ag NWs with the diameters from 80 nm to 150 nm. The fractal dimension of Au-Ag ANPs/Ag NWs is 1.69 due to macroscopic dendritic structures. Compared with single Ag NWs, the prepared Au-Ag ANPs/Ag NWs substrates show superior SERS performance because of higher surface roughness, the SERS active of Ag NWs and bimetallic synergistic effect caused by Au-Ag ANPs, so the limit of detections (LOD) of Au-Ag ANPs/Ag NWs SERS substrates toward detection of CV and AB 6B were as low as 10-16mol/L and 10-9mol/L, respectively. These results indicate that Au-Ag ANPs/Ag NWs substrates can be used for rapid and sensitive detection of CV and AB 6B and have great development potential for detection of illegal food additives and hazardous substances in the fields of environmental monitoring and food safety.

3.
J Ethnopharmacol ; 336: 118661, 2025 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-39159837

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Shuangdan Jiedu Decoction (SJD) is a formula composed of six Chinese herbs with heat-removing and detoxifying, antibacterial, and anti-inflammatory effects, which is clinically used in the therapy of various inflammatory diseases of the lungs including COVID-19, but the therapeutic material basis of its action as well as its molecular mechanism are still unclear. AIM OF THE STUDY: The study attempted to determine the therapeutic effect of SJD on LPS-induced acute lung injury (ALI), as well as to investigate its mechanism of action and assess its therapeutic potential for the cure of inflammation-related diseases in the clinical setting. MATERIALS AND METHODS: We established an ALI model by tracheal drip LPS, and after the administration of SJD, we collected the bronchoalveolar lavage fluid (BALF) and lung tissues of mice and examined the expression of inflammatory factors in them. In addition, we evaluated the effects of SJD on the cyclic guanosine monophosphate-adenosine monophosphate synthase -stimulator of interferon genes (cGAS-STING) and inflammasome by immunoblotting and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: We demonstrated that SJD was effective in alleviating LPS-induced ALI by suppressing the levels of pro-inflammatory cytokines in the BALF, improving the level of lung histopathology and the number of neutrophils, as well as decreasing the inflammatory factor-associated gene expression. Importantly, we found that SJD could inhibit multiple stimulus-driven activation of cGAS-STING and inflammasome. Further studies showed that the Chinese herbal medicines in SJD had no influence on the cGAS-STING pathway and inflammasome alone at the formulated dose. By increasing the concentration of these herbs, we observed inhibitory effects on the cGAS-STING pathway and inflammasome, and the effect exerted was maximal when the six herbs were combined, indicating that the synergistic effects among these herbs plays a crucial role in the anti-inflammatory effects of SJD. CONCLUSIONS: Our research demonstrated that SJD has a favorable protective effect against ALI, and its mechanism of effect may be associated with the synergistic effect exerted between six Chinese medicines to inhibit the cGAS-STING and inflammasome abnormal activation. These results are favorable for the wide application of SJD in the clinic as well as for the development of drugs for ALI from herbal formulas.


Asunto(s)
Lesión Pulmonar Aguda , Medicamentos Herbarios Chinos , Inflamasomas , Lipopolisacáridos , Proteínas de la Membrana , Nucleotidiltransferasas , Transducción de Señal , Animales , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/metabolismo , Lipopolisacáridos/toxicidad , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Nucleotidiltransferasas/metabolismo , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Ratones , Masculino , Transducción de Señal/efectos de los fármacos , Ratones Endogámicos C57BL , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Modelos Animales de Enfermedad , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Líquido del Lavado Bronquioalveolar/citología
4.
Food Chem ; 462: 141010, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-39217745

RESUMEN

In this study, we investigated how different proportions blends of Rhamnogalacturonan-I pectic polysaccharides and hesperidin impact the gut microbiota and metabolites using an in vitro simulated digestion and fermentation model. The results indicated that both of them could modulate the gut microbiota and produce beneficial metabolites. However, their blends in particular proportions (such as 1:1) exhibited remarkable synergistic effects on modulating the intestinal microenvironment, surpassing the effects observed with individual components. Specifically, these blends could benefit the host by increasing short-chain fatty acids production (such as acetate), improving hesperidin bioavailability, producing more metabolites (such as hesperetin, phenolic acids), and promoting the growth of beneficial bacteria. This synergistic and additive effect was inseparable from the role of gut microbiota. Certain beneficial bacteria, such as Blautia, Faecalibacterium, and Prevotella, exhibited strong preferences for those blends, thereby contributing to host health through participating in carbohydrate and flavonoid metabolism.


Asunto(s)
Bacterias , Microbioma Gastrointestinal , Hesperidina , Pectinas , Hesperidina/farmacología , Hesperidina/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Bacterias/metabolismo , Bacterias/genética , Bacterias/efectos de los fármacos , Bacterias/clasificación , Bacterias/aislamiento & purificación , Humanos , Pectinas/metabolismo , Pectinas/química , Pectinas/farmacología , Fermentación , Polisacáridos/farmacología , Polisacáridos/metabolismo , Polisacáridos/química , Ácidos Grasos Volátiles/metabolismo , Digestión , Modelos Biológicos
5.
Proc Natl Acad Sci U S A ; 121(38): e2401175121, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39250664

RESUMEN

Singlet oxygen (1O2) is important in the environmental remediation field, however, its efficient production has been severely hindered by the ultrafast self-quenching of the as-generated radical precursors in the Fenton-like reactions. Herein, we elaborately designed lamellar anthraquinone-based covalent organic frameworks (DAQ-COF) with sequential localization of the active sites (C═O) at molecular levels for visible-light-assisted peroxymonosulfate (PMS) activation. Theoretical and experimental results revealed that the radical precursors (SO5·-) were formed in the nearby layers with the migration distance less than 0.34 nm, via PMS donating electrons to the photogenerated holes. This interlayer synergistic effect eventually led to ultraefficient 1O2 production (14.8 µM s-1), which is 12 times that of the highest reported catalyst. As an outcome, DAQ-COF enabled the complete degradation of bisphenol A in 5 min with PMS under natural sunlight irradiation. This interlayer synergistic concept represents an innovative and effective strategy to increase the utilization efficiency of ultrashort-lived radical precursors, providing inspirations for subtle structural construction of Fenton-like catalysts.

6.
Sci Total Environ ; 953: 176034, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39236812

RESUMEN

PURPOSE: To explore the mechanisms of tolerance of Brassica napus to ultra-high concentration cadmium pollution and the synergistic effects of biochar (BC) and Arbuscular mycorrhizal fungi (AMF) on plant growth under cadmium (Cd) stress. RESULTS: The application of 5 % BC and inoculation with 10 g AMF significantly promoted the growth and development of B. napus. The combined application of BC and AMF (BC1A and BC2A) was better than the single application. At the Cd 200 mg/kg level, BC1A increased the fresh weight and Cd content of the above-ground parts of B. napus by 35.5 % and decreased by 21.20 %. The SOD and POD activities increased by 30.63 % and 73.37 %. The MDA and H2O2 contents decreased by 40.8 % and 69.99 %, soluble sugar content increased by 37.96 %. At the Cd 300 mg/kg level, BC1A increased the fresh weight and Cd content of the above-ground parts of B. napus by 32.8 % and decreased by 15.99 %. The SOD and POD activities increased by 39.06 % and 93.56 %. The MDA and H2O2 contents decreased by 28.39 % and 72.45 %, and the soluble sugar content increased by 21.16 %. Overall, both BC and AMF treatments alone or in combination (BC1A) were able to alleviate Cd stress and promote plant growth, with the combination of biochar and AMF being the most effective. Furthermore, transcriptome analyses indicated that BC may improve cadmium resistance in B. napus by significantly up-regulating the expression of genes related to peroxidase, photosynthesis, and plant MAPK signaling pathways. AMF may alleviate the toxicity of Cd stress on B. napus by up-regulating the expression of genes related to peroxisomes, phytohormone signaling, and carotenoid biosynthesis. The results of the study will provide support for ecological restoration technology in extremely heavy metal-polluted environments and provide some reference for the application and popularization of BC and AMF conjugation technology.

7.
J Hazard Mater ; 479: 135719, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39241363

RESUMEN

Hybrid systems combined eletrocatalysis and Fenton-like process attract a lot of attention due their outstanding performance and unique mechanism. Here, we proposed an efficient, cost-effective, and versatile electrochemical activation (ECA) system for efficient water purification, and intensively studied the synergistic effects between electrocatalysis and peroxymonosulfate (PMS)-based advanced oxidation. The ECA system achieved complete removal of 20 ppm tetracycline hydrochloride (TCH) in 15 min, with a rate constant of 0.338 min-1. Its performance was assessed across various operational parameters (PMS dosage, pH, applied voltage, electrode interval, temperature, co-existed ions, biomass, different oxidants), demonstrating its broad applicability and stability. Excellent degradation and mineralization for other 12 kinds of refractory organic pollutants were also achieved. The outstanding performance can be attributed to the synergistic effect in the system, in which electrocatalytic reduction of dissolved oxygen generated H2O2 and O2•-, boosting the number of reactive species, such as 1O2, by interacting with PMS. Furthermore, the presence of organic matter promotes electron transfer, amplifying the system's degradation capability. These findings not only highlight the ECA system's effectiveness in organic pollutant removal but also offer insights into the underlying degradation mechanisms, paving the way for future advancements in water purification technologies.

8.
Nutrients ; 16(17)2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39275332

RESUMEN

Exceeding a healthy weight significantly elevates the likelihood of developing type 2 diabetes (T2DM). A commercially available singular constituent, available as either purified vitexin or iso-vitexin, has been associated with a decreased risk of T2DM, but its synergistic effect has not been reported yet. Vitexin and iso-vitexin were extracted using an ethanol-based solvent from mung bean seed coat (MBCE) and subsequently purified using preparative liquid chromatography (Prep-LC). Eleven mixture ratios of vitexin and/or iso-vitexin were determined for their antioxidant and antihyperglycemic activities. The 1:1.5 ratio of vitexin to iso-vitexin from MBCE demonstrated the most synergistic effects for enzyme inhibition and glucose uptake in HepG2 cells within an insulin-resistant system, while these ratios exhibited a significantly lower antioxidant capacity than that of each individual component. In a gut model system, the ratio of 1:1.5 (vitexin and iso-vitexin) regulated the gut microbiota composition in overweight individuals by decreasing the growth of Enterobacteriaceae and Enterococcaceae, while increasing in Ruminococcaceae and Lachnospiraceae. The application of vitexin/iso-vitexin for 24 h fermentation enhanced a high variety of abundances of 21 genera resulting in five genera of Parabacteroides, Ruminococcus, Roseburia, Enterocloster, and Peptacetobacter, which belonged to the phylum Firmicutes, exhibiting high abundant changes of more than 5%. Only two genera of Proteus and Butyricicoccus belonging to Proteobacteria and Firmicutes decreased. The findings suggest that these phytochemicals interactions could have synergistic effects in regulating glycemia, through changes in antihyperglycemic activity and in the gut microbiota in overweight individuals. This optimal ratio can be utilized by industries to formulate more potent functional ingredients for functional foods and to create nutraceutical supplements aimed at reducing the risk of T2DM in overweight individuals.


Asunto(s)
Apigenina , Microbioma Gastrointestinal , Hipoglucemiantes , Sobrepeso , Semillas , Vigna , Apigenina/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Hipoglucemiantes/farmacología , Semillas/química , Masculino , Células Hep G2 , Diabetes Mellitus Tipo 2 , Antioxidantes/farmacología , Extractos Vegetales/farmacología , Femenino
9.
Nat Prod Bioprospect ; 14(1): 53, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39276287

RESUMEN

Currently, cocrystallization is a promising strategy for tailoring the physicochemical properties of active pharmaceutical ingredients. Theophylline, an alkaloid and the most primary metabolite of caffeine, is a readily available compound found in tea and coffee. It functions primarily as a bronchodilator and respiratory stimulant, making it a mainstay treatment for lung diseases like asthma. Theophylline's additional potential benefits, including anti-inflammatory and anticancer properties, and its possible role in neurological disorders, have garnered significant research interest. Cocrystal formation presents a viable approach to improve the physicochemical properties of theophylline and potentially mitigate its toxic effects. This review comprehensively explores several successful studies that utilized cocrystallization to favorably alter the physicochemical properties of theophylline or its CCF. Notably, cocrystals can not only enhance the solubility and bioavailability of theophylline but also exhibit synergistic effects with other APIs. The review further delves into the hydrogen bonding sites within the theophylline structure and the hydrogen bonding networks observed in cocrystal structures.

10.
Heliyon ; 10(17): e36223, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39281661

RESUMEN

The purpose of this study is to investigate the potential anticarcinogenic effects of three phytochemicals, namely Alpha-pinene (AP), Gamma-terpinene (GT), and P-cymene (PC), on melanoma cells (A2058 cell line). Additionally, the study aims to explore the synergistic activities of these phytochemicals with Dacarbazine, a chemotherapy drug. To understand the molecular mechanism involved in apoptosis induction in the A-2058 cell line, it was used AO/EB staining for apoptosis detection and cell cycle analysis, monitored through flow cytometry. It also determined the mRNA expression levels of different apoptosis-regulatory genes, including p53, Bax, NF-kB, Bcl-2, Bcl-xl, and caspase-3. The antitumor activities of these phytochemicals and their combinations were investigated in a subcutaneous mouse tumor model. The tumor diameter was 21.4 ± 1.1 mm in the Dacarbazine treatment group and 42.4 ± 3.1 mm in the control group. The antitumoral activities of AP and PC in the tumor model were similar to those of Dacarbazine. On the other hand, GT exhibited remarkable antitumoral activity, with a 1.75-fold reduction in tumor diameter compared to the Dacarbazine group. When different combinations of phytochemicals and Dacarbazine were used, the GT plus Dacarbazine treatment group was found to have a 3.5-fold reduction in tumor diameter compared to the Dacarbazine group. The tumor diameters in the Dacarbazine, AP plus GT, GT plus Dacarbazine, and AP plus Dacarbazine treatment groups were 21.4 ± 1.1, 7.6 ± 2.2, 8.6 ± 0.5, and 6.2 ± 1.9 mm, respectively.

11.
Mater Today Bio ; 28: 101223, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39290466

RESUMEN

Lanthanum (La)-based nanotherapeutics are therapeutically advantageous due to cytoplasmic oxygen species (ROS) levels for mediating intrinsic and extrinsic tumor cell apoptosis. While they have not been extensively explored for their potential to suppress malignancies in vivo. Correspondingly, we have formulated a unique lanthanum nanocarrier with high specific surface area, dendritic-divergent mesopores, importantly, exposing more active lanthanum sites. After surface PEGlytion and ICG loading in mesoporous channels, this fantastic nanoplatform can efficaciously enrich in malignant glioblastoma regions. Meaningfully, it can be sensitively dissociated for La ions release under weak acid (pH = 6.5) tumor microenvironment. Upon 808 nm light irradiation, high light-heat conversion efficiency is further proved, then this satisfied thermal in the tumor site progressively enhances ROS production by La ions. Owing to the synergistic oxidative therapy and photothermal therapy of our dendritic La nanoplatform, glioblastoma is efficaciously and synergistically prevented both in vitro and in vivo. All outcomes highlight the therapeutic potency of La based nanoplatform with radial mesopores to treat malignant cancer in vivo and encourage future translational exploration.

12.
J Agric Food Chem ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39291433

RESUMEN

Two endophytes from the same Ginkgo biloba host were isolated and cultured separately. Three new eremophilane sesquiterpenoids (1-3), three new furan derivates (6, 8-9), one new polyketide (10), and four known compounds (4, 5, 7, 11) from Paraphaeosphaeria sp. and two new 10-membered macrolides (12-13), a new liner polyketide (14), a new benzofuran (15), and six known compounds (16-21) from Nigrospora oryzae were isolated. The structures of the isolated compounds were determined by spectroscopic methods, NMR calculations, and ECD calculations. The compounds 3-7, 9-10, 12, and 14-17 showed significant antiphytopathogenic effects against mycotoxigenic Alternaria sp. comparable to the activity of nystatin (positive control). Compounds 2, 6, 8, 9, and 18 indicated inhibitions against phytopathogen Fusarium asiaticum with MICs < 10 µg/mL. In addition, the compounds with weak antifungal activities from two endophytes were mixed to test their antifungal activity. The results showed that the metabolites from two endophytes had synergistic antifungal effects, and the beneficial interactions between natural products can induce more antifungal effects against plant pathogens than that of single compounds.

13.
J Agric Food Chem ; 72(37): 20458-20469, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39230615

RESUMEN

Our previous study proved that epicatechin (EC) and ß-glucan (BG) from whole-grain highland barley synergistically modulate glucose metabolism in insulin-resistant HepG2 cells. However, the main target and the mechanism underlying the modulation of glucose metabolism in vivo remain largely unknown. In this study, cell transfection assay and microscale thermophoresis analysis revealed that EC and BG could directly bind to the insulin receptor (IR) and mammalian receptor for rapamycin (mTOR), respectively. Molecular dynamic analysis indicated that the key amino acids of binding sites were Asp, Met, Val, Lys, Ser, and Tys. EC supplementation upregulated the IRS-1/PI3K/Akt pathway, while BG upregulated the mTOR/Akt pathway. Notably, supplementation with EC + BG significantly increased Akt and glucose transporter type 4 (GLUT4) protein expressions, while decreasing glycogen synthase kinase 3ß (GSK-3ß) expression in liver cells as compared to the individual effects of EC and BG, indicating their synergistic effect on improving hepatic glucose uptake and glycogen synthesis. Consistently, supplementation with EC + BG significantly decreased blood glucose levels and improved oral glucose tolerance compared to EC and BG. Therefore, combined supplementation with EC and BG may bind to corresponding receptors, targeting synergistic activation of Akt expression, leading to the improvement of hepatic glucose metabolism and thereby ameliorating hyperglycemia in vivo.


Asunto(s)
Catequina , Glucosa , Hordeum , Hiperglucemia , Hígado , Ratones Endogámicos C57BL , beta-Glucanos , Hordeum/química , beta-Glucanos/farmacología , beta-Glucanos/química , Animales , Ratones , Catequina/farmacología , Catequina/administración & dosificación , Hígado/metabolismo , Hígado/efectos de los fármacos , Masculino , Humanos , Glucosa/metabolismo , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/metabolismo , Sinergismo Farmacológico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Transportador de Glucosa de Tipo 4/metabolismo , Transportador de Glucosa de Tipo 4/genética , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Glucógeno Sintasa Quinasa 3 beta/genética , Glucemia/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Células Hep G2
14.
Int J Biol Macromol ; : 135653, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39278430

RESUMEN

Alpha-amylase and beta-amylase coexist as mixtures in industrial production, and the two amylases have active synergistic effects when they approach each other. These effects are due to enhanced enzyme binding affinity for the substrate and the rate of particle hydrolysis. Here, we report the allosteric mechanism of this synergistic effect in α- and ß-amylase mixtures. The assay showed higher activity after mixing α- and ß-amylase. Molecular docking showed that α- and ß-amylase create a stable dual-enzyme complex with high binding energy, and that complex formation does not affect the exposure of respective active sites. ß-Amylase is specifically bound to the B domain of α-amylase, and the dynamic plasticity of the B domain makes it move spatially, and this adjustment leads to a more open conformation in the active site of α-amylase. Because the enzymes binding make the complex more stable, the degree to which the relative activity of the dual-enzyme complex is inhibited is significantly reduced. After enzyme hydrolysis, the products maltose and glucose accumulate and produce competitive inhibition, which explains the relative activity decrease of the later-stage dual-enzyme cooperation. Structural characterization by FT-IR and CD spectroscopy did not reveal significant changes in respective secondary structures after enzyme binding.

15.
Artículo en Inglés | MEDLINE | ID: mdl-39279657

RESUMEN

The successful filling of bone defects remains challenging due to the incongruity between bone graft materials and the dynamic process of bone healing. Developing multifunctional materials matching the dynamic process of bone healing offers a viable solution to the current dilemma. Lines of evidence have shown that engineering osteoimmunomodulatory biomaterials can modulate the function of immune cells and thus promote bone regeneration. Herein, we utilized silk fibroin (SF) and polyglycolic acid (PGA) to create a PGA-SF core-shell fibrous scaffold, incorporating interleukin-4 (IL-4) and tricalcium phosphate (TCP) as a codelivery system (PGA/TCP-SF/IL-4), aiming to achieve an initial rapid release of IL-4 and sustained release of TCP. The PGA/TCP-SF/IL-4 scaffold mimicked the native bone structure and showed superior tenacity in the wetting regime. In vitro studies demonstrated that the PGA/TCP-SF/IL-4 scaffold significantly reduced the inflammatory response by upregulating the M2 macrophages, created a favorable microenvironment for osteogenesis, and facilitated osteogenic differentiation and mineralization. Implantation of the PGA/TCP-SF/IL-4 scaffold into the rat skull defect model notably increased the formation of new bones. IL-4 and TCP acted synergistically in attenuating inflammation and enhancing osteogenic differentiation. Overall, this multifunctional scaffold comprehensively considers the various demands in the bone defect region, which might have a significant potential for application in bone reconstruction.

16.
Sci Total Environ ; 953: 176138, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39260476

RESUMEN

In an era marked by unprecedented anthropogenic change, marine systems are increasingly subjected to interconnected and dynamic external stressors, which profoundly reshape the behavior and resilience of marine ecological components. Nevertheless, despite widespread recognition of the significance of stressor interactions, there persist notable knowledge deficits in quantifying their interactions and the specific biological consequences that result. To bridge this crucial gap, this research detected and examined the causal relationships between five key exogenous stressors in a complex estuarine ecosystem. Furthermore, a Bayesian Hierarchical Spatio-temporal modeling framework was proposed to quantitatively evaluate the distinct, interactive, and globally sensitive effects of multiple stressors on the population dynamics of a crucial fish species: Harpadon nehereus. The results showed that interactions were detected between fisheries pressure (FP), the Pacific Decadal Oscillation index (PDO), runoff volume (RV), and sediment load (SL), with five of these interactions producing significant synergistic effects on H. nehereus biomass. The SL*PDO and RV*PDO interactions had positive synergistic effects, albeit through differing processes. The former interaction amplified the individual effects of each stressor, while the latter reversed the direction of the original impact. Indeed overall, the synergistic effect of multiple stressors was not favorable, with FP in particular posing the greatest threat to H. nehereus population. This threat was more pronounced at high SL or negative PDO phases. Therefore, local management efforts aimed at addressing multiple stressors and protecting resources should consider the findings. Additionally, although the velocity of climate change (VoCC) failed to produce significant interactions, changes in this stressor had the most sensitive impacts on the response of H. nehereus population. This research strives to enhance the dimensionality, generalizability, and flexibility of the quantification framework for marine multi-stressor interactions, aiming to foster broader research collaboration and jointly tackle the intricate pressures facing marine ecosystems.

17.
Chemosphere ; 364: 143227, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39218258

RESUMEN

In this study, visible light-activated photocatalyst oxygen-doped C3N4@Bi12O17Cl2 (OCN@BOC) and Fe(VI) coupling system was proposed for the efficient degradation of bisphenol A (BPA). The comprehensive characterization of the OCN@BOC photocatalyst revealed its excellent photogenerated carrier separation rate in heterogeneous structures. The OCN@BOC/Fe(VI)/Vis system exhibited a remarkable BPA removal efficiency of over 84% within 5 min. Comparatively, only 37% and 59% of BPA were degraded by single OCN@BOC and Fe(VI) in 5 min, respectively. Reactive species scavenging experiments, phenyl sulfoxide transformation experiments, and electron paramagnetic resonance experiments confirmed the involvement of superoxide radicals (⋅O2-), singlet oxygen (1O2), as well as iron(V)/iron(IV) (Fe(V)/Fe(IV)) species in the degradation process of BPA. Furthermore, density functional theoretical calculations and identification of intermediates provided insights into the potential degradation mechanism of BPA during these reactions. Additionally, simulation evaluations using an ecological structure activity relationship model demonstrated that the toxicity of BPA to the ecological environment was mitigated during its degradation process. This study presented a novel strategy for removing BPA utilizing visible light photocatalysts, highlighting promising applications for practical water environment remediation with the OCN@BOC/Fe(VI)/Vis system.

18.
Cureus ; 16(8): e66295, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39238681

RESUMEN

BACKGROUND: The dwindling antibiotic reserve owing to augmented drug-resistant bacteria is a major handicap for treating physicians. Klebsiella pneumoniae, a gram-negative encapsulated member of the Enterobacteriaceae family, is one such pathogenic bacteria. Carbapenemase-producing Klebsiella pneumoniae is globally recognized as one of the most critical bacterial threats to public health due to its extremely limited treatment options. Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections pose therapeutic challenges due to simultaneous resistance to various other groups of antibiotics. In this study, we have evaluated the synergistic effect of fosfomycinagainst CRKP isolates when used in combination with colistin by applying the Checkerboard method. METHODS: A laboratory-based prospective study was conducted in the Department of Microbiology, JSS Hospital, Mysuru, for a period of one year after obtaining ethical clearance. Klebsiella pneumoniae isolates obtained from clinical samples were screened for carbapenem resistance by the VITEK-2 compact system (bioMérieux, Marcy-l'Étoile, France). The minimum inhibitory concentration (MIC) of colistin and fosfomycin was individually ascertained by broth microdilution (BMD). Finally, the synergistic activity of the fosfomycin-colistin combination was determined by the BMD-based Checkerboard method. RESULTS: Among the 50 CRKP isolates, 36 (72%) isolates showed synergism, eight (16%) isolates showed indifference and six (12%) isolates showed partial synergism, while none of them showed additivity and antagonism by the Checkerboard method. These results are found to be statistically significant (chi-square value of 116.204 and p-value of < 0.00001). CONCLUSION: This study showed a promising in-vitro synergy between the drugs fosfomycin and colistin by Checkerboard BMD testing protocol. Colistin being a reserve antibiotic, monotherapy comes with the limitations of higher chances of resistance as well as toxicity, which can be overcome by combination therapy, thereby decreasing CRKP-associated mortality rates and delivering holistic patient benefit.

19.
Future Med Chem ; : 1-14, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235081

RESUMEN

Aim: This work aimed to synthesize a new pyrimidine PYB01 with potential application against antimicrobial resistance.Materials & methods: PYB01 was synthesized through condensation reaction between 3a and 3b. The antimicrobial evaluation was carried out using the microdilution method in Mueller-Hinton Agar and in silico predictions using different software.Results: PYB01 has moderate antibiotic activity and high capacity to efficiently modulate antibiotic resistance in Staphylococcus aureus. In silico evaluations demonstrated that PYB01 is probably an allosteric inhibitor of Protein Binding Penicilin 2a and modulates the action of oxacillin by decreasing the minimum inhibitory concentration by 64-times. PYB01 demonstrate a good pharmacokinetic profile and toxicological.Conclusion: PYB01 has great potential to go further in investigating its use against antimicrobial resistance.


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Artículo en Inglés | MEDLINE | ID: mdl-39235080

RESUMEN

Quinazolinone derivatives are an important class of pharmaceutical and pesticide intermediates, which are generally synthesized starting with the condensation reaction between aldehydes and 2-aminobenzamide to obtain corresponding intermediates and then oxidized to obtain the products. Although some catalysts have been developed currently for the synthesis of quinazolinone derivatives, their catalytic efficiency is relatively low because only the oxidative catalytic sites of the catalyst have been focused on. Herein, we synthesized three new polyoxometalate-based metal-organic frameworks, [CuI4(4,4'-bipy)7(Hn-1PMo12-nVnO40)]·2H2O (n = 1-3), which were formed by coordinating a Cu(I)-bipy complex with different Keggin-type phosphomolybdic acids. An important feature of these compounds is that they possess proton and multioxidative active sites [Cu(I) center and V(V) center]; thus, we applied them to the catalytic synthesis of quinazolinone derivatives. The results indicate that compound 3 has an excellent catalytic activity. Based on density functional theory calculations, it is speculated that protons participate in the aldehyde amine condensation reaction, which changes the reaction pathway and reduces the activation energy from 55.1 to 31.4 kcal/mol, thereby increasing the reaction rate significantly. Interestingly, Raman spectra and electron paramagnetic resonance measurements indicate the presence of CuIIOO• and •O2- during the oxidative dehydrogenation process, which facilitates the rapid consumption of 2-phenyl-2,3-dihydroquinazolin-4(1H)-one intermediates, thereby promoting the chemical reaction to move toward the positive direction. Thanks to the synergistic effect of multicatalytic sites, compound 3 achieved highly efficient catalytic synthesis of quinazolinones with 99% yield in 1 h.

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