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Toxicology and Applied Pharmacology Jun 2024Colitis-associated cancer (CAC) is an aggressive subtype of colorectal cancer that can develop in ulcerative colitis patients and is driven by chronic inflammation and...
Colitis-associated cancer (CAC) is an aggressive subtype of colorectal cancer that can develop in ulcerative colitis patients and is driven by chronic inflammation and oxidative stress. Current chemotherapy for CAC, based on 5-fluorouracil and oxalipltin, is not fully effective and displays severe side effects, prompting the search for alternative therapies. Dimethylfumarate (DMF), an activator of the nuclear factor erythroid 2-related factor 2 (Nrf2), is a potent antioxidant and immunomodelatrory drug used in the treatment of multiple sclerosis and showed a strong anti-inflammatory effect on experimental colitis. Here, we investigated the chemotherapeutic effect of DMF on an experimental model of CAC. Male NMRI mice were given two subcutaneous injections of 1,2 Dimethylhydrazine (DMH), followed by three cycles of dextran sulfate sodium (DSS). Low-dose (DMF30) and high-dose of DMF (DMF100) or oxaliplatin (OXA) were administered from the 8th to 12th week of the experiment, and then the colon tissues were analysed histologically and biochemically. DMH/DSS induced dysplastic aberrant crypt foci (ACF), oxidative stress, and severe colonic inflammation, with a predominance of pro-inflammatory M1 macrophages. As OXA, DMF30 reduced ACF multiplicity and crypt dysplasia, but further restored redox status, and reduced colitis severity by shifting macrophages towards the anti-inflammatory M2 phenotype. Surprisingly, DMF100 exacerbated ACF multiplicity, oxidative stress, and colon inflammation, likely through NRF2 and p53 overexpression in colonic inflammatory cells. DMF had a dual effect on CAC. At low dose, DMF is chemotherapeutic and acts as an antioxidant and immunomodulator, whereas at high dose, DMF is pro-oxidant and exacerbates colitis-associated cancer.
PubMed: 38945373
DOI: 10.1016/j.taap.2024.117018 -
International Journal of Biological... Jun 2024The objective of the present research was to develop chitosan-coated nanoliposomes using a modified heating method as a delivery system for simultaneous encapsulation of...
The objective of the present research was to develop chitosan-coated nanoliposomes using a modified heating method as a delivery system for simultaneous encapsulation of caffeine and roselle anthocyanin to fortify beverage. Response surface methodology was used to ascertain the optimized formulation, aiming to maximize the encapsulation efficiency, minimize the particle size, and maximize the zeta potential. The liposomes fabricated under the optimized conditions (lecithin to cholesterol ratio of 13 and wall to core ratio of 2.16) showed encapsulation efficiency values of 66.73 % for caffeine and 97.03 % for anthocyanin, with a size of 268.1 nm and a zeta potential of -39.11 mV. Fourier transform infrared spectroscopy confirmed the formation of hydrogen bonds between the polar sites of lecithin and the loaded core compounds. Thermal analysis suggested the successful encapsulation of the caffeine and anthocyanin. Transmission and scanning electron microscopy images confirmed a uniform spherical shape with a smooth surface. Fortifying the model beverage with the liposome and the chitosan-coated nanoliposome revealed higher values of encapsulation efficiency of anthocyanin (70.33 ± 3.11 %), caffeine (86.37 ± 2.17 %) and smaller size (280.5 ± 0.74 nm) of the chitosan-coated nanoliposomes at the end of 60th days. A hedonic sensory test of the fortified beverage with chitosan-coated nanoliposomes confirmed an improvement in the organoleptic properties of the beverage by masking its bitterness (receiving three more sensory scores in perceiving the bitterness intensity). Overall, our study indicates that the high potential of the chitosan-coated nanoliposomes for the simultaneous loading of the caffeine and anthocyanin, as well as their possible application in food and beverage formulations.
PubMed: 38945345
DOI: 10.1016/j.ijbiomac.2024.133469 -
European Journal of Pharmacology Jun 2024The increased incidence of obesity, which become a global health problem, requires more functional food products with minor side and excellent effects. Calebin A (CbA)...
The increased incidence of obesity, which become a global health problem, requires more functional food products with minor side and excellent effects. Calebin A (CbA) is a non-curcuminoid compound, which is reported to be an effective treatment for lipid metabolism and thermogenesis. However, its ability and mechanism of action in improving obesity-associated hyperglycemia remain unclear. This study was designed to explore the effect and mechanism of CbA in hyperglycemia via improvement of inflammation and glucose metabolism in the adipose tissue and liver in high-fat diet (HFD)-fed mice. After 10 weeks fed HFD, obese mice supplemented with CbA (25 and 100 mg/kg) for another 10 weeks showed a remarkable reducing adiposity and blood glucose. CbA modulated M1/M2 macrophage polarization, ameliorated inflammatory cytokines, and restored adiponectin as well as Glut 4 expression in the adipose tissue. In the in vitro study, CbA attenuated pro-inflammatory markers while upregulated anti-inflammatory IL-10 in LPS + IFNγ-generated M1 phenotype macrophages. In the liver, CbA attenuated steatosis, inflammatory infiltration, and protein levels of inflammatory TNF-α and IL-6. Moreover, CbA markedly upregulated Adiponectin receptor 1, AMPK, and insulin downstream Akt signaling to improve glycogen content and increase Glut2 protein. These findings indicated that CbA may be a novel therapeutic approach to treat obesity and hyperglycemia phenotype targeting on adipose inflammation and hepatic insulin signaling.
PubMed: 38945287
DOI: 10.1016/j.ejphar.2024.176789 -
Chemosphere Jun 2024Sediment microbial fuel cells (SMFCs) generate bioelectricity from benthic sediments and thus providing both bioelectricity generation and sediment remediation. However,...
Sediment microbial fuel cells (SMFCs) generate bioelectricity from benthic sediments and thus providing both bioelectricity generation and sediment remediation. However, the high internal resistance of the cathode leads to a low power output, which requires research on cathode treatment. In this study, we explored the influence of light irradiation on bioelectricity production and nutrient removal in the SMFC system. The microcosm experiment of the SMFC system was designed with artificial illumination of 500 lux (light-SMFC) and compared with dark conditions of 15 lux (dark-SMFC), which showed that the current increases during photoperiods. The study reveals that light-illuminated SMFC consistently produced the highest voltage, with the highest voltage (553 mV) being 1.3 times higher than the dark-SMFC (440 mV). The polarization curves show a significant reduction in internal cathodic resistance under light condition, resulting in increased voltage generation. The light-SMFC exhibits the highest maximum power density of 35.93 mW/m, surpassing the dark SMFC of 31.13 mW/m. It was found that light illumination in the SMFC system increases oxygen availability in the cathodic region, which supports the oxygen reduction reaction (ORR) process. At the same time, the high bioelectricity output contributes to the highest sediment remediation by greatly reducing the chemical oxygen demand (COD) and phosphate (PO-P) concentrations. The study highlights the potential of light illumination in mitigating cathodic limitation to improve SMFC performance and nutrient removal.
PubMed: 38945220
DOI: 10.1016/j.chemosphere.2024.142720 -
Cancer Letters Jun 2024The tumor microenvironment (TME) of prostate cancer (PCa) is characterized by high levels of immunosuppressive molecules, including cytokines and chemokines. This...
The tumor microenvironment (TME) of prostate cancer (PCa) is characterized by high levels of immunosuppressive molecules, including cytokines and chemokines. This creates a hostile immune landscape that impedes effective immune responses. The interleukin-1 (IL-1) receptor antagonist (IL1RN), a key anti-inflammatory molecule, plays a significant role in suppressing IL-1-related immune and inflammatory responses. Our research investigates the oncogenic role of IL1RN in PCa, particularly its interactions with muscarinic acetylcholine receptor 4 (CHRM4), and its involvement in driving immunosuppressive pathways and M2-like macrophage polarization within the PCa TME. We demonstrate that following androgen deprivation therapy (ADT), the IL1RN-CHRM4 interaction in PCa activates the MAPK/AKT signaling pathway. This activation upregulates the transcription factors E2F1 and MYCN, stimulating IL1RN production and creating a positive feedback loop that increases CHRM4 abundance in both PCa cells and M2-like macrophages. This ADT-driven IL1RN/CHRM4 axis significantly enhances immune checkpoint markers associated with neuroendocrine differentiation and treatment-resistant outcomes. Higher serum IL1RN levels are associated with increased disease aggressiveness and M2-like macrophage markers in advanced PCa patients. Additionally, elevated IL1RN levels correlate with better clinical outcomes following immunotherapy. Clinical correlations between IL1RN and CHRM4 expression in advanced PCa patients and neuroendocrine PCa organoid models highlight their potential as therapeutic targets. Our data suggest that targeting the IL1RN/CHRM4 signaling could be a promising strategy for managing PCa progression and enhancing treatment responses.
PubMed: 38945201
DOI: 10.1016/j.canlet.2024.217090 -
Plant Physiology and Biochemistry : PPB Jun 2024The phytohormones cytokinins are essential mediators of developmental and environmental signaling, primarily during cell division and endophytic interactions, among...
The phytohormones cytokinins are essential mediators of developmental and environmental signaling, primarily during cell division and endophytic interactions, among other processes. Considering the limited understanding of the regulatory mechanisms that affect the growth and bioactivity of the medicinal plant Nepeta nuda (Lamiaceae), our study aimed to explore how cytokinins influence the plant's metabolic status. Exogenous administration of active cytokinin forms on in vitro N. nuda internodes stimulated intensive callus formation and de novo shoot regeneration, leading to a marked increase in biomass. This process involved an accumulation of oxidants, which were scavenged by peroxidases using phenolics as substrates. The callus tissue formed upon the addition of the cytokinin 6-benzylaminopurine (BAP) acted as a sink for sugars and phenolics during the allocation of nutrients between the culture medium and regenerated plants. In accordance, the cytokinin significantly enhanced the content of polar metabolites and their respective in vitro biological activities compared to untreated in vitro and wild-grown plants. The BAP-mediated accumulation of major phenolic metabolites, rosmarinic acid (RA) and caffeic acid (CA), corresponded with variations in the expression levels of genes involved in their biosynthesis. In contrast, the accumulation of iridoids and the expression of corresponding biosynthetic genes were not significantly affected. In conclusion, our study elucidated the mechanism of cytokinin action in N. nuda in vitro culture and demonstrated its potential in stimulating the production of bioactive compounds. This knowledge could serve as a basis for further investigations of the environmental impact on plant productivity.
PubMed: 38945096
DOI: 10.1016/j.plaphy.2024.108884 -
Journal of Colloid and Interface Science Jun 2024Rechargeable magnesium battery is regarded as the promising candidate for the next generation of high-specific-energy storage systems. Nevertheless, issues related to...
Rechargeable magnesium battery is regarded as the promising candidate for the next generation of high-specific-energy storage systems. Nevertheless, issues related to severe Mg-Cl dissociation at the electrolyte-electrode interface impede the insertion of Mg into most materials, leading to severe polarization and low utilization of Mg-storage electrodes. In this study, a metal-organic polymer (MOP) Ni-TABQ (Ni-coordinated tetramino-benzoquinone) with superior surface catalytic activity is proposed to achieve the high-capacity Mg-MOP battery. The layered Ni-TABQ cathode, featuring a unique 2D π-d linear conjugated structure, effectively reduces the dissociation energy of MgCl clusters at the Janus interface, thereby facilitating Mg insertion. Due to the high utilization of active sites, Ni-TABQ achieves high capacities of 410 mAh/g at 200 mA g, attributable to a four-electron redox process involving two redox centers, benzoid carbonyls, and imines. This research highlights the importance of surface electrochemical processes in rechargeable magnesium batteries and paves the way for future development in multivalent metal-ion batteries.
PubMed: 38945027
DOI: 10.1016/j.jcis.2024.06.151 -
Journal of Colloid and Interface Science Jun 2024Since the chiral emission of excited states is observed on carbon dots (CDs), exploration towards the design and synthesis of chiral CDs nanomaterials with circularly...
Since the chiral emission of excited states is observed on carbon dots (CDs), exploration towards the design and synthesis of chiral CDs nanomaterials with circularly polarized luminescence (CPL) properties has been at a brisk pace. In this regard, the "host and guest" co-assembly strategy based on the combination of CDs and chiral templates has been of unique interest recently for its convenient operation, multicolor tunable CPL, and wide application of prepared CDs-composited materials in optoelectronic devices and information encryption. However, the existing chiral templates that match perfectly with chiral CDs exhibiting optical activity both in ground and excited states are rather scarce. In this work, we synthesize the chiral CDs that could induce the spontaneous supramolecular self-assembly of N-(9-fluorenylmethox-ycarbonyl) (Fmoc)-protected glutamic acid to form chiral hydrogels with helical nanostructure. The co-assembled hydrogels show powerful chiral template function, which not only enable chiral CDs with a luminescence dissymmetry factor (g) up to 10, but also have universal chiral transfer to inserted dye molecules, realizing full-color CPL and Förster resonance energy transfer (FRET) CPL as well as the distinction between left and right circularly polarized light. This CPL-active template based on chiral CDs enriches the design scenario of chiral functionalized nanomaterials.
PubMed: 38945025
DOI: 10.1016/j.jcis.2024.06.208 -
Inorganic Chemistry Jun 2024Electromagnetic wave absorption performance is strictly dependent on attenuation and impedance matching, which are directly influenced by the ratio of MXene/MAX in the...
Electromagnetic wave absorption performance is strictly dependent on attenuation and impedance matching, which are directly influenced by the ratio of MXene/MAX in the multilayer structured MXene/MAX composites. However, there is still a challenge to achieve collaborative optimization of dielectric loss and impedance matching by precisely regulating the proportional relationship of MXene/MAX. Herein, V-based MXene/MAX heterostructure composites with different VC/VAlC ratios were successfully synthesized by rationally controlling the temperature and time of the hydrothermal reaction. Experimental results indicated that VC-100 °C-1 harvested the balance between reduced impedance matching and enhanced dielectric losses, which was attributed to the mildly enhanced conduction loss and polarization loss. The first principles indicated that abundant electrons migrate from the V atoms of the MXene to the C atoms of the MAX phase. The charge redistributed and accumulated at the interface, exciting the increase in the dielectric loss of VC-100 °C-1. As a result, the VC-100 °C-1 heterostructure composite had an excellent electromagnetic absorption effect with a minimum reflection loss of -50.06 dB and a wide effective absorption bandwidth of 4.0 GHz (12.72-16.72 GHz). This work provides a valuable experience for the development of efficient MXene-based microwave absorbing materials.
PubMed: 38944846
DOI: 10.1021/acs.inorgchem.4c01583 -
Cell Reports Jun 2024The basement membrane (BM) is an extracellular matrix that plays important roles in animal development. A spatial heterogeneity in composition and structural properties...
The basement membrane (BM) is an extracellular matrix that plays important roles in animal development. A spatial heterogeneity in composition and structural properties of the BM provide cells with vital cues for morphogenetic processes such as cell migration or cell polarization. Here, using the Drosophila egg chamber as a model system, we show that the BM becomes heterogeneous during development, with a reduction in Collagen IV density at the posterior pole and differences in the micropattern of aligned fiber-like structures. We identified two AdamTS matrix proteases required for the proper elongated shape of the egg chamber, yet the molecular mechanisms by which they act are different. Stall is required to establish BM heterogeneity by locally limiting Collagen IV protein density, whereas AdamTS-A alters the micropattern of fiber-like structures within the BM at the posterior pole. Our results suggest that AdamTS proteases control BM heterogeneity required for organ shape.
PubMed: 38944833
DOI: 10.1016/j.celrep.2024.114399