Exploration of the Molecular Mechanism of Curcuma aromatica Salisb's Anticolorectal Cancer Activity via the Integrative Approach of Network Pharmacology and Experimental Validation.

Curcuma aromatica Salisb (Cur), a well-known herbal medicine, has a wide spectrum of anti-inflammatory, anticarcinogenic, and antioxidant activities. However, the roles of its active compounds and potential mechanisms in colorectal cancer remain unknown. This research utilized network pharmacology and experimental validation to explore the possible mechanisms by which Cur protects against colorectal cancer. The active compounds of Cur and related genes for colorectal cancer were obtained from public databases. The DrugBank database was used to search for anticolorectal cancer drugs licensed through the FDA and their targets, and a "drug-component-target" relationship network was created using the Cytoscape program. The String database produced the PPI network. The ability of these active ingredients to bind to core targets was confirmed by molecular docking using AutoDock Vina. Cell and animal experiments were then carried out. A total of 274 targets were obtained from Cur, 49 of which were potential therapeutic targets. Four key targets, PTGS2, AKT1, TP53, and estrogen receptor 1 (ESR1), were screened via the PPI network and the FDA drug-target network. Molecular docking results revealed that Cur had strong binding abilities to these targets. In vivo and in vitro experiments demonstrated that Cur suppressed the development of colorectal cancer by regulating its targets (PTGS2, AKT1, TP53, and ESR1), which play crucial roles in promoting apoptosis and suppressing cell proliferation, migration, and invasion. Collectively, Cur protects against colorectal cancer by regulating the AKT1/PTGS2/ESR1 and P53 pathways, which lays the groundwork for further research and clinical applications of Cur in colorectal cancer therapy.

Antitumor Effect of Poplar Propolis on Human Cutaneous Squamous Cell Carcinoma A431 Cells.

Propolis is a gelatinous substance processed by western worker bees from the resin of plant buds and mixed with the secretions of the maxillary glands and beeswax. Propolis has extensive biological activities and antitumor effects. There have been few reports about the antitumor effect of propolis against human cutaneous squamous cell carcinoma (CSCC) A431 cells and its potential mechanism. CCK-8 assays, label-free proteomics, RT-PCR, and a xenograft tumor model were employed to explore this possibility. The results showed that the inhibition rate of A431 cell proliferation by the ethanol extract of propolis (EEP) was dose-dependent, with an IC50 of 39.17 µg/mL. There were 193 differentially expressed proteins in the EEP group compared with the control group (p < 0.05), of which 103 proteins (53.37%) were upregulated, and 90 proteins (46.63%) were downregulated. The main three activated and suppressed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were extracellular matrix (ECM)-receptor interaction, amoebiasis, cell adhesion molecules (CAMs), nonalcoholic fatty liver disease (NAFLD), retrograde endocannabinoid signaling, and Alzheimer's disease. The tumor volume of the 100 mg/kg EEP group was significantly different from that of the control group (p < 0.05). These results provide a theoretical basis for the potential treatment of human CSCC A431 cell tumors using propolis.

Development, Physicochemical Properties, and Antibacterial Activity of Propolis Microcapsules.

Propolis is a well-known natural antibacterial substance with various biological activities, such as anti-inflammatory and antioxidant activity. However, applications of propolis are limited due to its low water solubility. In this study, propolis microcapsules were developed with a core material of ethanol extract of propolis and shell materials of gum arabic and ß-cyclodextrin using a spray-drying technique. The optional processing formula, particle size distribution, morphology, dissolution property, and antibacterial activity of propolis microcapsules were determined. The results showed that the optional processing obtained an embedding rate of 90.99% propolis microcapsules with an average particle size of 445.66 ± 16.96 nm. The infrared spectrogram and thermogravimetric analyses showed that propolis was embedded in the shell materials. The propolis microcapsules were continuously released in water and fully released on the eighth day, and compared to propolis, the microcapsules exhibited weaker antibacterial activity. The minimum inhibitory concentrations (MICs) of propolis microcapsules against Escherichia coli and Staphylococcus aureus were 0.15 and 1.25 mg/mL, and their minimum bactericidal concentrations (MBCs) were 0.3 and 1.25 mg/mL, respectively. This water-soluble propolis microcapsule shows the potential for use as a sustained-release food additive, preservative, or drug.

Antioxidant and antibacterial activity of Apis laboriosa honey against Salmonella enterica serovar Typhimurium.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a common food-borne pathogen that commonly causes gastroenteritis in humans and animals. Apis laboriosa honey (ALH) harvested in China has significant antibacterial activity against Staphylococcus aureus, Escherichia coli, and Bacillus subtilis. We hypothesize that ALH has antibacterial activity against S. Typhimurium. The physicochemical parameters, minimum inhibitory and bactericidal concentrations (MIC and MBC) and the possible mechanism were determined. The results showed that there were significantly different physicochemical parameters, including 73 phenolic compounds, among ALH samples harvested at different times and from different regions. Their antioxidant activity was affected by their components, especially total phenol and flavonoid contents (TPC, TFC), which had a high correlation with antioxidant activities except for the O2- assay. The MIC and MBC of ALH against S. Typhimurium were 20-30% and 25-40%, respectively, which were close to those of UMF5+ manuka honey. The proteomic experiment revealed the possible antibacterial mechanism of ALH1 at IC50 (2.97%, w/v), whose antioxidant activity reduced the bacterial reduction reaction and energy supply, mainly by inhibiting the citrate cycle (TCA cycle), amino acid metabolism pathways and enhancing the glycolysis pathway. The results provide a theoretical basis for the development of bacteriostatic agents and application of ALH.

CTRP15 promotes macrophage cholesterol efflux and attenuates atherosclerosis by increasing the expression of ABCA1

C1q tumor necrosis factor–related protein 15 (CTRP15), a newly identified myokine, is closely implicated in cardiovascular disease. However, the role of CTRP15 in atherosclerosis is still unclear. This study aims to determine the role of CTRP15 in atherosclerosis and explore the underlying mechanisms. Our findings revealed that lentivirus-mediated CTRP15 overexpression significantly decreased atherosclerotic plaque lesions and increased reverse cholesterol transport (RCT) efficiency and circulating HDL-C levels in apolipoprotein E-deficient (apoE−/−) mice. Consistently, in vitro, overexpression of CTRP15 also inhibited intracellular lipid accumulation and promoted cholesterol efflux from macrophages. Mechanistically, CTRP15 decreased the expression of miR-101-3p by upregulating T-cadherin, thereby facilitating ABCA1 expression and cholesterol efflux. In summary, these data indicate that CTRP15 inhibits the development of atherosclerosis by enhancing RCT efficiency and increasing plasma HDL-C levels via the T-cadherin/miR-101-3p/ABCA1 pathway. Targeting CTRP15 may serve as a novel and promising therapeutic strategy for atherosclerotic cardiovascular diseases. (AU)

Baicalein inhibits macrophage lipid accumulation and inflammatory response by activating the PPARγ/LXRα pathway.

Lipid accumulation and inflammatory response are two major risk factors for atherosclerosis. Baicalein, a phenolic flavonoid widely used in East Asian countries, possesses a potential atheroprotective activity. However, the underlying mechanisms remain elusive. This study was performed to explore the impact of baicalein on lipid accumulation and inflammatory response in THP-1 macrophage-derived foam cells. Our results showed that baicalein up-regulated the expression of ATP binding cassette transporter A1 (ABCA1), ABCG1, liver X receptor α (LXRα), and peroxisome proliferator-activated receptor γ (PPARγ), promoted cholesterol efflux, and inhibited lipid accumulation. Administration of baicalein also reduced the expression and secretion of TNF-α, IL-1ß, and IL-6. Knockdown of LXRα or PPARγ with siRNAs abrogated the effects of baicalein on ABCA1 and ABCG1 expression, cholesterol efflux, lipid accumulation as well as pro-inflammatory cytokine release. In summary, these findings suggest that baicalein exerts a beneficial effect on macrophage lipid accumulation and inflammatory response by activating the PPARγ/LXRα signaling pathway.

CTRP15 promotes macrophage cholesterol efflux and attenuates atherosclerosis by increasing the expression of ABCA1.

C1q tumor necrosis factor-related protein 15 (CTRP15), a newly identified myokine, is closely implicated in cardiovascular disease. However, the role of CTRP15 in atherosclerosis is still unclear. This study aims to determine the role of CTRP15 in atherosclerosis and explore the underlying mechanisms. Our findings revealed that lentivirus-mediated CTRP15 overexpression significantly decreased atherosclerotic plaque lesions and increased reverse cholesterol transport (RCT) efficiency and circulating HDL-C levels in apolipoprotein E-deficient (apoE-/-) mice. Consistently, in vitro, overexpression of CTRP15 also inhibited intracellular lipid accumulation and promoted cholesterol efflux from macrophages. Mechanistically, CTRP15 decreased the expression of miR-101-3p by upregulating T-cadherin, thereby facilitating ABCA1 expression and cholesterol efflux. In summary, these data indicate that CTRP15 inhibits the development of atherosclerosis by enhancing RCT efficiency and increasing plasma HDL-C levels via the T-cadherin/miR-101-3p/ABCA1 pathway. Targeting CTRP15 may serve as a novel and promising therapeutic strategy for atherosclerotic cardiovascular diseases.

CTRP1 decreases ABCA1 expression and promotes lipid accumulation through the miR-424-5p/FoxO1 pathway in THP-1 macrophage-derived foam cells.

Prevention of ATP binding cassette transporter A1 (ABCA1)-dependent cholesterol efflux leads to lipid accumulation in macrophages and atherosclerosis development. C1q tumor necrosis factor-related protein 1 (CTRP1), a conserved paralog of adiponectin, has been shown to aggravate atherosclerosis via its proinflammatory property. However, very little is known about its effects on ABCA1 expression and macrophage lipid accumulation. In the current studies, we found that CTRP1 downregulated ABCA1 expression, inhibited cholesterol efflux to apoA-I and promoted lipid accumulation in THP-1 macrophage-derived foam cells. Forkhead box O1 (FoxO1), a transcriptional repressor of ABCA1, was identified as a direct target of miR-424-5p. Mechanistically, CTRP1 attenuated miR-424-5p levels and then augmented FoxO1 expression in the nucleus, which led to downregulation of ABCA1 expression and inhibition of cholesterol efflux. In conclusion, these findings suggest that CTRP1 restrains cholesterol efflux and facilitates macrophage lipid accumulation through the miR-424-5p/FoxO1/ABCA1 signaling pathway, thereby providing a novel mechanistical insight into its proatherosclerotic action.

Effects of air-impingement jet drying on drying kinetics and quality retention of tomato slices.

The purpose was to explore the drying kinetics, the moisture effective diffusivities, color, total polyphenols, lycopene and antioxidant activities of dried tomato slices by air-impingement jet drying (AIJD). The results showed that high temperature increased the drying rate, and Modified Page model accurately predicted the AIJD characteristics of tomato slices. AIJD is better than hot air drying in shortening drying time, enhancing drying rate and decreasing the loss of total polyphenols, lycopene and antioxidant capacity of tomato slices. Tomato slices dried by AIJD also showed higher lightness and redness. Lycopene content and antioxidant activity of tomato slices dried by AIJD were increased by higher drying temperature. Based on experimental data, AIJD at 80 °C can be used in tomato drying process due to the advantages in drying efficiency and content of bioactive compounds. This study will provide helpful information for the production of high quality of dried tomato products.

Removal of acetaminophen through direct electron transfer by reactive Mn2O3: Efficiency, mechanism and pathway.

Mn2O3 with certain oxidative reactivity, was fabricated via sol-gel method and applied for the removal of acetaminophen (APAP). The mechanism of APAP oxidation was revealed in depth through electrochemical tests and X-ray photoelectron spectroscopy (XPS). Moreover, the selective abatement of various organic contaminants contained different functional groups by Mn2O3 was investigated through linear free energy relationship (LFER) estimated with peak potentials (Eop) of these organic contaminants. Under acidic condition, APAP could be effectively eliminated by Mn2O3. The open circuit potential (OCP) and zeta potential tests illustrate that the oxidative reactivity of Mn2O3 is associated to the surface acid-base behavior of Mn2O3 and its surface charge situation. The XPS experiments and Mn leaching results imply that Mn(III) could capture electron from APAP and release Mn2+ to aqueous phase. The intermediates could be ascribed to fragmentation of acetamido radicals and phenoxy radicals, both of which were formed through electron transfer from APAP to Mn2O3. The reactive Mn2O3 shows selective oxidation of different contaminants in the electron transfer process. LFER analysis indicates good negative linear correlation between lnk1 and Eop of various pollutants. The efficiency of Mn2O3 in the elimination of APAP and selective oxidation of different contaminants suggest some new insights for transformation of APAP and other electron-rich pollutants in the environments.

Sorting nexins: A novel promising therapy target for cancerous/neoplastic diseases.

Sorting nexins (SNXs) are a diverse group of cytoplasmic- and membrane-associated phosphoinositide-binding proteins containing the PX domain proteins. The function of SNX proteins in regulating intracellular protein trafficking consists of endocytosis, endosomal sorting, and endosomal signaling. Dysfunctions of SNX proteins are demonstrated to be involved in several cancerous/neoplastic diseases. Here, we review the accumulated evidence of the molecular structure and biological function of SNX proteins and discuss the regulatory role of SNX proteins in distinct cancerous/neoplastic diseases. SNX family proteins may be a valuable potential biomarker and therapeutic strategy for diagnostics and treatment of cancerous/neoplastic diseases.

Degradation of bisphenol A by electro-enhanced heterogeneous activation of peroxydisulfate using Mn-Zn ferrite from spent alkaline Zn-Mn batteries.

Mn-Zn ferrite (Mn0.6Zn0.4Fe2O4) was prepared by a gel method using spent alkaline Zn-Mn batteries as raw materials and employed as catalyst to degrade bisphenol A (BPA) by electro-enhanced heterogeneous activation of peroxydisulfate (PDS). The effects of initial pH, current density, PDS concentration, and Mn-Zn ferrite dosage on BPA removal were investigated. The formation of reactive radicals was verified by electron paramagnetic resonance (EPR) spectroscopy. The results of radical quenching experiments indicate that surface-bound sulfate and hydroxyl radicals played an important role in BPA removal. The stability of Mn0.6Zn0.4Fe2O4 catalyst was investigated by cycling experiments, which indicates Mn0.6Zn0.4Fe2O4 is stable and can be reused. This work also provides an alternative way for the reutilization of spent alkaline Zn-Mn batteries.

Investigation into the impact of diagnostic ultrasound with microbubbles on the capillary permeability of rat hepatomas.

Ultrasound-targeted microbubble destruction (UTMD) takes advantage of transiently increased capillary permeability to enhance the release of tumor-specific drugs from blood vessels into sonicated tumor tissues. However, the application of focused ultrasound is limited because of the lack of an appropriate image-monitoring system. In this study, hepatoma-bearing Sprague-Dawley rats were insonicated with low-frequency diagnostic ultrasound and injected with Evans Blue (EB) dye and microbubbles through their tail veins to test changes in capillary permeability. We studied how the mechanical index, sonication duration and the injected microbubble (MB) concentration affect the hepatoma vascular permeability by quantitatively evaluating the EB delivery efficiency. Confocal laser scanning microscopy was used to observe the deposition of red fluorescence-dyed EB in tumor tissues. In addition, P-selectin, a type of biochemical marker that reflects vascular endothelial cell activation, was identified using an immunoblotting analysis. The experimental results reveal that EB delivery efficiency in tumor tissues was greater in groups with the diagnostic ultrasound-mediated UTMD (8.40 ± 0.71 %ID/g) than in groups without UTMD (1.73 ± 0.19 %ID/g) and EB delivery efficiency could be affected by MI, sonication duration and MB dose. The immunoblotting analysis indicates that diagnostic ultrasound-induced UTMD results in the vascular endothelial cell activation to increase capillary permeability, justifying the high quantity of EB deposited in tumor tissues.

Saturated hydrogen saline protects rats from acute lung injury induced by paraquat.

BACKGROUND: Paraquat (PQ) intoxication causes lung oxidative stress damage. Saturated hydrogen saline, a newly explored antioxidant, has been documented to play a powerful antioxidant role in preventing oxidative stress damage. This study aimed to investigate the protective effects and the possible mechanisms of intoxication on rats with acute lung injury (ALI) caused by paraquat poisoning. METHODS: Thirty PQ poisoned rats were randomly divided into a PQ intoxication group (intoxication group), a saturated hydrogen saline intervention group (intervention group), and a control group, with 10 rats in each group. The first two groups accepted an intragastric administration of PQ at a dose of 50 mg/kg for every single rat, and the control group was fed with a same volume of normal saline. Five mL/kg of saturated hydrogen saline was given to the intervention group three times a day by peritoneal injection for three days after intoxication. Arterial blood gas was detected on the third day. The rats were executed and their lungs were taken for measurement of wet dry weight ratio, homogenate malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OhdG). Histological changes of the lungs were also observed. RESULTS: Compared with the control group, the intoxication group had more serious hypoxemia, greater wet/dry weight ratio, higher MDA level, higher expression of 8-OhdG and more severe lung damage (P<0.01 or P<0.05). However, after intervention with saturated hydrogen saline, poisoned animals turned to have lighter hypoxemia, smaller wet/dry weight ratio, lower MDA level, lower expression of 8-OhdG, and milder lung damage (P<0.01 or P<0.05). CONCLUSIONS: Saturated hydrogen saline is effective in preventing acute lung injury caused by PQ. Possibly, it can neutralize toxic oxygen radicals selectively and alleviate the oxidative stress injury induced by PQ.