Determination of dimethylated nucleosides in serum from colorectal cancer patients by hydrophilic interaction liquid chromatography-tandem mass spectrometry.

RNA modifications play a crucial regulatory role in a variety of biological processes and are closely related to numerous diseases, including cancer. The diversity of metabolites in serum makes it a favored biofluid for biomarkers discovery. In this work, a robust and accurate hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) approach was established for simultaneous determination of dimethylated nucleosides in human serum. Using the established method, we were able to accurately quantify the concentrations of N6-2'-O-dimethyladenosine (m6Am), N2,N2-dimethylguanosine (m2,2G), and 5,2'-O-dimethyluridine (m5Um) in serum samples from 53 healthy controls, 57 advanced colorectal adenoma patients, and 39 colorectal cancer (CRC) patients. The results showed that, compared with healthy controls and advanced colorectal adenoma patients, the concentrations of m6Am and m2,2G were increased in CRC patients, while the concentration of m5Um was decreased in CRC patients. These results indicate that these three dimethylated nucleosides could be potential biomarkers for early detection of colorectal cancer. Interestingly, the level of m5Um was gradually decreased from healthy controls to advanced colorectal adenoma patients to CRC patients, indicating m5Um could also be used to evaluate the level of malignancy of colorectal tumor. In addition, this study will contribute to the investigation on the regulatory mechanisms of RNA dimethylation in the onset and development of colorectal cancer.

Corrigendum: Efficacy and functionality of sugarcane original vinegar on mice.

[This corrects the article DOI: 10.3389/fmicb.2023.1224666.].

Efficacy and functionality of sugarcane original vinegar on mice.

Introduction: Due to their bioactive compounds and beneficial health effects, functional foods and plant-based natural medicines are widely consumed. Due to its bioactivities, vinegar is one of them that helps humans. Sugarcane original vinegar (SOV) is a special vinegar made from sugarcane as a raw material through biological fermentation processes. Methods: The objective of this study was to assess the effects of sugarcane original vinegar on growth performance, immune response, acute oral toxicity, bacterial reverse mutation, mammalian erythrocyte micronucleus, mouse spermatogonial chromosome aberration, mammalian bone marrow cell chromosome aberration changes, and serum characteristics in mice. Distortion parameters were used to assess its safety, and at the same time, the functionality of SOV was monitored during experimentation. Results: The results show that the SOV has no damage or inhibitory effect on the bone marrow red blood cells of mice and no mutagenic or distortion-inducing effects on the bone marrow cell chromosomes or spermatogonia chromosomes, so it is safe to eat. SOV can improve blood lipids and reduce blood lipid content. Discussion: The study results provide data basis for the intensive processing of sugarcane and the development of high-value SOV products. Sugarcane original vinegar has a beneficial impact on performance, immune response, and chromosomal aberration. The production application influences the vinegar's quality and, consequently, its health benefits.

Characterization of the Pure Black Tea Wine Fermentation Process by Electronic Nose and Tongue-Based Techniques with Nutritional Characteristics.

Wine is an alcoholic beverage, consisting of several compounds in various ranges of concentrations. Wine quality is usually assessed by a sensory panel of trained personnel. Electronic tongues (e-tongues) and electronic noses (e-noses) have been established in recent years to assess the quality of beverages and foods. Response surface and electronic analysis tools were used to examine the quality of black tea wine. The results indicated the optimum initial sugar level (25 °Brix), yeast addition (0.5%), and fermentation temperature (25 °C) for Golden Peony black tea wine. The black tea wine produced under these conditions with 14.0% vol alcohol has as an orange-red color, full wine and tea flavor, and mild and mellow taste. The sourness of the wine was most affected by fermentation factors-yeast addition, fermentation temperature, and initial sugar level. Alcohols, aldehydes, ketones, and alkanes contributed to most of the volatile components under the influence of yeast addition and fermentation temperature. In contrast, nitrogen oxides, aromatics, and organic sulfides contributed under the influence of the initial sugar level. This study provided a facilitated strategy for obtaining the optimum black tea wine fermentation process through electronic nose and tongue-based techniques. The analysis of wines requires new technologies able to detect various different compounds simultaneously, providing worldwide information about the sample instead of information about specific compounds.

Vinegar: A potential source of healthy and functional food with special reference to sugarcane vinegar.

Vinegar is one of the most widely used acidic condiments. Recently, rapid advances have been made in the area of vinegar research. Different types of traditional vinegar are available around the globe and have many applications. Vinegar can be made either naturally, through alcoholic and then acetic acid fermentation, or artificially, in laboratories. Vinegar is the product of acetic acid fermentation of dilute alcoholic solutions, manufactured by a two-step process. The first step is the production of ethanol from a carbohydrate source such as glucose, which is carried out by yeasts. The second step is the oxidation of ethanol to acetic acid, which is carried out by acetic acid bacteria. Acetic acid bacteria are not only producers of certain foods and drinks, such as vinegar, but they can also spoil other products such as wine, beer, soft drinks, and fruits. Various renewable substrates are used for the efficient biological production of acetic acid, including agro and food, dairy, and kitchen wastes. Numerous reports on the health advantages associated with vinegar ingredients have been presented. Fresh sugarcane juice was fermented with wine yeast and LB acetate bacteria to develop a high-quality original sugarcane vinegar beverage. To facilitate the current study, the bibliometric analysis method was adopted to visualize the knowledge map of vinegar research based on literature data. The present review article will help scientists discern the dynamic era of vinegar research and highlight areas for future research.

Comparison of Different Drying Methods for Asparagus [Asparagus cochinchinensis (Lour.) Merr.] Root Volatile Compounds as Revealed Using Gas Chromatography Ion Mobility Spectrometry.

Asparagus [Asparagus cochinchinensis (Lour.) Merr.] is a traditional herbal medicine plant commonly used to nourish yin, moisten dryness, and clear fire cough symptoms. Drying is an excellent option to conserve food materials, i.e., grains, fruits, vegetables, and herbs, reducing the raw materials volume and weight. This study aims to evaluate different drying approaches that could increase the value of asparagus, particularly as an ingredient in fast foods or as nutraceutical byproducts. The volatile components of asparagus roots were analyzed by using headspace-gas chromatography-ion mobility spectroscopy under different drying conditions, i.e., natural drying (ND) at ambient air temperature in the dark, well-ventilated room, temperature range 28-32°C, blast or oven drying at 50°C, heat pump or hot-air drying at temperature 50°C and air velocity at 1.5 ms-1 and vacuum freeze-drying at the temperature of -45°C and vacuum pressure of 10-30 Pa for 24 h. The findings revealed that the various drying processes had multiple effects on the color, odor index, and volatile compounds of the asparagus roots. As a result of the investigations, multiple characteristics of components, therefore, exploitation and comparison of various flavors; a total of 22 compounds were identified, such as alcohols, ketones, aldehydes, acids, esters, heterocyclic, and terpene. The present findings may help understand the flavor of the processed asparagus roots and find a better option for drying and processing.

Characterization of the aromatic profile of purple passion fruit (Passiflora edulis Sims) during ripening by HS-SPME-GC/MS and RNA sequencing.

Passion fruit is a tropical liana of the Passiflora family that is commonly consumed throughout the world due to its attractive aroma and flavor. However, very limited information is available on the mechanism of aroma formation and composition of the passion fruit during ripening. Therefore, HS-SPME-GC/MS combined with transcriptome analysis was used to study the mechanism of aroma formation during passion fruit ripening. The profile analyzed included 148 volatile organic compounds (VOCs) and related differentially expressed genes (DEGs). Compared with SA, 85 VOCs and related DEGs were identified as significantly upregulated at the SB and SC stages, including esters, alcohols, ketones, hydrocarbons, alkanes, and aldehydes. Two main pathways, ester and amino acid metabolism, and related genes were analyzed with VOC biosynthesis in passion fruit. This study is the first analysis of passion fruit VOC formation and provides new insights into the flavor mechanism and quality breeding of passion fruit.

Influence of polysaccharide-based edible coatings on enzymatic browning and oxidative senescence of fresh-cut lettuce.

Fresh-cut lettuce has a short shelf-life due to enzymatic browning and oxidative senescence. The present study investigated effects of polysaccharide-based edible coatings (alginate, chitosan, and carrageenan) on enzymatic browning and antioxidant defense system of fresh-cut lettuces during cold storage (4°C) for 15 days. The results showed that three coatings could inhibit enzymatic browning through maintaining total phenolics (TP) content and decreasing polyphenol oxidase (PPO) and phenylalanine ammonialyase (PAL) activities. These coatings also reduced phospholipase D (PLD) and lipoxygenase (LOX) activities, lowered malondialdehyde (MDA) content, and enhanced antioxidant enzymes (superoxide dismutase, SOD; peroxidase, POD; catalase, CAT; ascorbate peroxidase, APX) activities. Besides, all coatings positively affected sensory properties of fresh-cut lettuces after 3 days storage. Additionally, among three coating treatments, chitosan coating had the most positive effects on quality of fresh-cut lettuce and was the most suitable coating for retarding enzymatic browning and alleviating membrane oxidative damage. These results indicated that polysaccharide-based edible coatings were helpful to maintain quality, inhibit enzymatic browning, and postpone senescence of fresh-cut lettuce.

Comprehensive evaluation on tailor-made deep eutectic solvents (DESs) in extracting tea saponins from seed pomace of Camellia oleifera Abel.

Tea saponins from Camellia oleifera Abel. seed pomace are new sources of commercial saponins. This study established an eco-friendly and efficient extraction method for tea saponins from C. oleifera seed pomace. A ternary deep eutectic solvent (DES) composed of l-proline, glycerol and sucrose (4:10:1 in molar ratio, abbreviated as PGS-5) achieved the highest extraction yield of tea saponins among all screened DESs. A maximum extraction yield of 23.22 ± 0.28% was obtained using PGS-5 under the optimized extraction time, DES concentration and liquid-solid ratio. Through ultraviolet, Fourier transform infrared spectroscopy and ultrahigh-performance liquid chromatography-Q Exactive HF mass spectroscopy, as well as analyses of antioxidant and antimicrobial activities, it was determined that extracted saponins did not altered during processing. Therefore, PGS-5 can serve as a solvent to obtain stable and beneficial tea saponins from C. oleifera seed pomace.

Phenolic and Volatile Compounds in the Production of Sugarcane Vinegar.

This study aimed to explore the dynamic variations in the phenolic and volatile organic compounds of sugarcane vinegar subjected to different production processes. The determination of phenolic and volatile organic compounds was performed by UPLC-MS and solid phase micro extraction (SPME) coupled with gas chromatography combined with mass spectrometry (GC-MS). The complete fermentation process of sugarcane lasted nine days, and production of vinegar of up to 3.04% (w/v), total acids, and 4.1° alcoholicity was accomplished. Various phenolic compounds of sugarcane juice (non-sterilized) and those of alcoholic and acetic acid fermentation were obtained after nine days of fermentation. These were benzoic acid (2.024, 1.002, and 1.027 mg L-1), ferulic acid (0.060, 0.205, and 1.124 mg L-1), quinic acid (0.019, 0.074, and 0.031 mg L-1), chlorogenic acid (0.349, 1.635, and 1.217 mg L-1), apigenin (0.002, 0.099, and 0.004 mg L-1), kaempferol (0.003, 0.336, and 0.003 mg L-1), caffeic acid (-, 0.005, and 0.005 mg L-1), luteolin (0.003, 0.323, and 0.005 mg L-1), and p-coumaric acid (0.018, 0.015, and 0.027 mg L-1). Forty-five volatile organic compounds were also identified. The sugarcane juice can be commercialized as an alternative to wine as it presents characteristics of an alcoholic fermented beverage.

The Role of 1-Methylcyclopropene in the regulation of ethylene biosynthesis and ethylene receptor gene expression in Mangifera indica L. (Mango Fruit).

Mango (Mangifera indica L.) is respiratory climacteric fruit that ripens and decomposes quickly following their harvest. 1-methylcyclopropene (1-MCP) is known to affect the ripening of fruit, delaying the decay of mango stored under ambient conditions. The objective of this study was to clarify the role of 1-MCP in the regulation of ethylene biosynthesis and ethylene receptor gene expression in mango. 1-MCP significantly inhibited the 1-aminocyclopropane-1-carboxylic acid (ACC) content. The activity of ACC oxidase (ACO) increased on days 6, 8, and 10 of storage, whereas delayed ACC synthase (ACS) activity increased after day 4. The two homologous ethylene receptor genes, ETR1 and ERS1 (i.e., MiETR1 and MiERS1), were obtained and deposited in GenBank® (National Center for Biotechnology Information-National Institutes of Health [NCBI-NIH]) (KY002681 and KY002682). The MiETR1 coding sequence was 2,220 bp and encoded 739 amino acids (aa). The MiERS1 coding sequence was 1,890 bp and encoded 629 aa, similar to ERS1 in other fruit. The tertiary structures of MiETR1 and MiERS1 were also predicted. MiERS1 lacks a receiver domain and shares a low homology with MiETR1 (44%). The expression of MiETR1 and MiERS1 mRNA was upregulated as the storage duration extended and reached the peak expression on day 6. Treatment with 1-MCP significantly reduced the expression of MiETR1 on days 4, 6, and 10 and inhibited the expression of MiETR1 on days 2, 4, 6, and 10. These results indicated that MiETR1 and MiERS1 had important functions in ethylene signal transduction. Treatment with 1-MCP might effectively prevent the biosynthesis of ethylene, as well as ethylene-induced ripening and senescence. This study presents an innovative method for prolonging the storage life of mango after their harvest through the regulation of MiETR1 and MiERS1 expression.

Polyphenols and Alkaloids in Byproducts of Longan Fruits (Dimocarpus Longan Lour.) and Their Bioactivities.

The longan industry produces a large amount of byproducts such as pericarp and seed, resulting in environmental pollution and resource wastage. The present study was performed to systematically evaluate functional components, i.e., polyphenols (phenolics and flavonoids) and alkaloids, in longan byproducts and their bioactivities, including antioxidant activities, nitrite scavenging activities in simulated gastric fluid and anti-hyperglycemic activities in vitro. Total phenolic and total flavonoid contents in pericarp were slightly higher than those in seeds, but seeds possessed higher alkaloid content than pericarp. Four polyphenolic substances, i.e., gallic acid, ethyl gallate, corilagin and ellagic acid, were identified and quantified using high-performance liquid chromatography. Among these polyphenolic components, corilagin was the major one in both pericarp and seed. Alkaloid extract in seed showed the highest DPPH radical scavenging activity and oxygen radical absorbance capacity. Nitrite scavenging activities were improved with extract concentration and reaction time increasing. Flavonoids in seed and alkaloids in pericarp had potential to be developed as anti-hyperglycemic agents. The research result was a good reference for exploring longan byproducts into various valuable health-care products.

Fermentation process optimization and chemical constituent analysis on longan (Dimocarpus longan Lour.) wine.

Based on single factor and orthogonal experiments, optimal fermentation conditions for longan wine were Saccharomyces cerevisiae strain of Lalvin KD, juice content of 70% and alcohol content of 10°. Sixteen amino acids were detected. Proline, alanine, glutamic acid and aspartic acid contents were relatively high. Sixty-three volatile aroma compounds were identified using solid-phase micro extraction and gas chromatography (SPME-GC). Ethyl lactate content was the highest, followed by octanoic acid ethyl ester, isoamyl alcohol and decanoic acid ethyl ester. Main functional components were polysaccharides. Longan wine polysaccharide (LWP) with molecular weight 10-30 kDa exhibited the highest hypoglycemic and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activities. 10-30 kDa polysaccharides mainly consisted of glucose, mannose, galactose, arabinose, galacturonic acid and glucuronic acid in molar ratio of 167.72:3.38:3.13:3.46:2.33:1. Infrared and nuclear magnetic resonance spectra confirmed that the sugar ring of 10-30 kDa polysaccharides was in the 〈beta〉-configuration.

Combined Delivery and Anti-Cancer Activity of Paclitaxel and Curcumin Using Polymeric Micelles.

Paclitaxel (PTX) is efficacious in treating various solid tumors. However, the severe adverse effects of its present formulation (Cremophor EL and ethanol) and the development of drug resistance by the activation of nuclear factor-κB (NF-κB) reduce the anti-tumor activities of PTX. Curcumin (Cur) demonstrates anti-tumor activity by means of antiangiogenesis and induction of apoptosis as well as suppression of the activity of NF-κB. Therefore, to improve its antitumor activity and eliminate the toxicity of the commercial formulation of PTX, we prepared biodegradable monomethoxy poly(ethyleneglycol)-poly(ε-caprolactone) (MPEG-PCL) micelles to co-deliver PTX and Cur using a solid dispersion method. The mixed PTX and Cur polymeric micelles (PTX-Cur-M) produced were monomorphous micelles of 38 nm in diameter that released PTX and Cur for an extended period of time and induced cell apoptosis in vitro. In addition, the PTX-Cur-M exhibited anti-angiogenic activity in vitro and in vivo. Furthermore, the therapeutic efficacy of PTX-Cur-M in a mouse model of colon cancer was evaluated. PTX-Cur-M micelles produced significantly more inhibition of tumor growth than Cur micelles (Cur-M) and PTX micelles (PTX-M) alone at the same dose (P < 0.05 and P < 0.05, respectively). Immunohistochemical and immunofluorescent analyses demonstrated that PTX-Cur-M enhanced tumor cell apoptosis and inhibited angiogenesis to a greater extent than control treatment. Our data suggested that PTX-Cur-M may have potential clinical applications in cancer therapy.

[Effect of basic fibroblast growth factor on endogenous neural stem cell in rat cerebral cortex with global cerebral ischemia-reperfusion].

The present paper is aimedto investigate the effect of basic fibroblast growth factor (bFGF) on proliferation, migration and differentiation of endogenous neural stem cell in rat cerebral cortex with global brain ischemia-reperfusion. A global brain ischemia-reperfusion model was established. Immunohistochemistry was used to observe the pathological changes and the expression of BrdU and Nestin in cerebral cortex. RT-PCR was used to measure the NSE mRNA in brain tissue. The results of measurements indicated that in sham operation group, there was no positive cell in cerebral cortex, and the content of NSE mRNA did not change. In the operation group, the expression of BrdU and Nestin increased significantly at the end of the 3rd day, and peaked on the 7th day. NSE mRNA expression did not significantly increase. In bFGF group, compared with sham operation group and model group, the number of BrdU-positive and Nestin-positive cells increased significantly at each time point (P<0. 05), and peaked at the end of the 11th day, and the content of NSE mRNA increased significantly (P<0. 05). This research demonstrated that the proliferation of endogenous neural stem cells in situ could be induced by global cerebral ischemia and reperfu- sion, and could be promoted and extended by bFGF. In additiion, bFGF might promote endogenous neural stem cells differentiated into neurons.

Effects of quercetin on the proliferation of breast cancer cells and expression of survivin in vitro.

Quercetin is a hydrophobic agent with potential anticancer activity. The aim of the present study was to observe the effects of quercetin on the proliferation of the breast cancer cell line MCF-7 and the gene expression of survivin. The molecular mechanism underlying the antiproliferative effect of quercetin was also investigated. MCF-7 breast cancer cells were treated with various concentrations of quercetin. The inhibitory effect of quercetin on proliferation was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and the inhibition rate was calculated. Cellular apoptosis was detected by immunocytochemistry and survivin mRNA expression levels were observed using reverse transcription-polymerase chain reaction (RT-PCR). Western blot analysis was used to analyze changes in the expression levels of survivin protein. Quercetin induced the apoptosis of MCF-7 cells and inhibited the proliferation of the MCF-7 breast cancer cells in a time- and concentration-dependent manner. The mRNA and protein expression levels of survivin were reduced as the concentration of quercetin increased. Quercetin inhibited the growth of MCF-7 cells and promoted apoptosis by inducing G0/ G1 phase arrest. It also regulated the expression of survivin mRNA in MCF-7 cells, which may be the mechanism underlying its antitumor effect.

Improving the anti-colon cancer activity of curcumin with biodegradable nano-micelles.

Curcumin (Cur) showed an antitumor effect by anti-angiogenesis and the induction of apoptosis. However, curcumin is limited in clinical applications by its hydrophobicity. Therefore, improving the water-solublilty and antitumor effect of curcumin are very meaningful. In this work, biodegradable monomethoxy poly(ethylene glycol)poly(lactide) copolymer (MPEG-PLA) micelles were employed to deliver curcumin by a self-assembly method. The obtained curcumin loaded polymeric micelles (Cur/MPEG-PLA) with a drug loading of 8% were monodisperse and ∼30 nm in diameter, which could release curcumin in an extended period in vitro and in vivo. In addition, Cur/MPEG-PLA showed a larger effect on cell growth inhibition and the induction of cell apoptosis than free curcumin in vitro. Furthermore, the therapy efficiency of Cur/MPEG-PLA on a colon cancer mouse model was evaluated in detail. Cur/MPEG-PLA could cause a more significant inhibitory effect on colon tumor growth than free curcumin with the same dose (P < 0.05 or P < 0.05, respectively), which indicated that Cur/MPEG-PLA could improve the antitumor effect of curcumin in vivo. Immunohistochemical and immunofluorescent analysis showed that Cur/MPEG-PLA could induce more tumor cell apoptosis, and inhibit more angiogenesis than the free drug group. Besides, Cur/MPEG-PLA exhibited a larger anti-angiogenesis effect in vivo. Finally, the anti-lung metastasis efficiency of Cur/MPEG-PLA on the colon cancer model was evaluated. Cur/MPEG-PLA could cause a more significant inhibitory effect on lung metastasis than free curcumin with the same dose (P < 0.05), which indicates that Cur/MPEG-PLA could improve the anti-lung metastasis effect of curcumin in vivo. Our data suggested Cur/MPEG-PLA may have potential clinical applications in colon cancer therapy.

Effect of tea polyphenols on the adhesion of highly metastatic human lung carcinoma cell lines to endothelial cells in vitro.

AIM: Tea polyphenols are known to play roles in critical steps of human lung carcinoma cell metastasis. For understanding the mechanisms whereby they inhibit tumor metastasis, the present study was conducted to investigate their effects on the adhesion of highly metastatic lung carcinoma cell lines (PG cells) to endothelial cells (EC cells) and adhesion molecule expression in vitro. METHODS: The expression of CD44 or CD54 in the PG cells was detected by flow cytometry and adhesion of PG cells to EC cells was assessed by confocal microscopy double fluorescence staining. RESULTS: The results showed that tea polyphenols: (1) inhibited the expression of CD44 and CD54, two important adhesion molecules in the PG cells in a dose-dependent manner; (2) significantly blocked the adhesion of PG cells to EC cells not only in a state of rest but also when active; and (3) influenced CD44 and CD54 expression during the adhesion process of PG cells to EC cells. CONCLUSION: The data indicated that the blocking role of tea polyphenols in the adhesion of PG cells to EC cells is related to CD44 and CD54. The mechanism of tea polyphenol prevention of human lung carcinoma metastasis might be through inhibiting adhesion molecule expression to block cancer cell adhesion.

Anticancer effect and mechanism of polymer micelle-encapsulated quercetin on ovarian cancer.

Encapsulation of hydrophobic agents in polymer micelles can improve the water solubility of cargos, contributing to develop novel drugs. Quercetin (QU) is a hydrophobic agent with potential anticancer activity. In this work, we encapsulated QU into biodegradable monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles and tried to provide proof-of-principle for treating ovarian cancer with this nano-formulation of quercetin. These QU loaded MPEG-PCL (QU/MPEG-PCL) micelles with drug loading of 6.9% had a mean particle size of 36 nm, rendering the complete dispersion of quercetin in water. QU inhibited the growth of A2780S ovarian cancer cells on a dose dependent manner in vitro. Intravenous administration of QU/MPEG-PCL micelles significantly suppressed the growth of established xenograft A2780S ovarian tumors through causing cancer cell apoptosis and inhibiting angiogenesis in vivo. Furthermore, the anticancer activity of quercetin on ovarian cancer cells was studied in vitro. Quercetin treatment induced the apoptosis of A2780S cells associated with activating caspase-3 and caspase-9. MCL-1 downregulation, Bcl-2 downregulation, Bax upregulation and mitochondrial transmembrane potential change were observed, suggesting that quercetin may induce apoptosis of A2780S cells through the mitochondrial apoptotic pathway. Otherwise, quercetin treatment decreased phosphorylated p44/42 mitogen-activated protein kinase and phosphorylated Akt, contributing to inhibition of A2780S cell proliferation. Our data suggested that QU/MPEG-PCL micelles were a novel nano-formulation of quercetin with a potential clinical application in ovarian cancer therapy.

High mobility group nucleosomal binding domain 2 protein protects bladder epithelial cells from Klebsiella pneumoniae invasion.

Due to the predominance of multiple-antibiotic-resistant Klebsiella pneumoniae strains, the search for new approaches for the prevention of K. pneumoniae infections is now under intensive investigation. The objective of the present study was to investigate the effects of high mobility group nucleosomal binding domain 2 (HMGN2) protein, which acts on the bladder epithelial cells T 24, on the invasion of K. pneumoniae 03183 and explore its possible mechanisms. Pretreatment with HMGN2 significantly reduced K. pneumoniae 03183 uptake by T 24 cells. In T 24 cells, there were no detectable cytotoxic effects of HMGN2 at any concentration between 32 and 256 µg/ml after 2 h incubation. HMGN2 exhibited no appreciable antibacterial activity against K. pneumoniae 03183. Fluorescence microscopy and flow cytometry analysis revealed that HMGN2 blocked K. pneumoniae 03183-induced actin polymerization. K. pneumoniae 03183-induced phosphorylation of extracellular signal-regulated kinase (ERK) and cofilin were prevented by pretreatment with HMGN2. These results indicated that pretreatment with HMGN2 inhibited cofilin phosphorylation and then induced actin disruption which may block ERK phosphorylation. These changes led to inhibition of K. pneumoniae 03183 invasion of T 24 bladder epithelial cells.