Role of NF-κB in cardiac changes of obstructive sleep apnoea rabbits treated by mandibular advancement device.

BACKGROUND: Obstructive sleep apnoea (OSA) is an independent risk factor for cardiovascular diseases. We aimed to investigate the role of nuclear factor-kappa B (NF-κB) in the changes of cardiac structures in OSA rabbits treated by mandibular advancement device (MAD). METHODS: Eighteen male New Zealand white rabbits aged 6 months were randomly divided into three groups: control group, group OSA and group MAD. Hyaluronate gel was injected into the soft palate of the rabbits in group OSA and group MAD to induce OSA. The cone beam computer tomography (CBCT) of the upper airway and polysomnography (PSG) was performed to ensure successful modelling. CBCT and PSG were applied again to detect the effects of MAD treatment. All animals were induced to sleep in a supine position for 4-6 h a day for 8 weeks. Then the levels of NF-κB, Interleukin 6 (IL-6), Interleukin 10 (IL-10) and the proportion of myocardial fibrosis (MF) were detected. RESULTS: The higher activation of NF-κB, IL-6 and IL-10 were found in the OSA group than in the control group, leading to the increase of collagen fibres compared with the control group. Furthermore, the apnoea-hypopnea index (AHI) was positively correlated with the above factors. There were no significant differences between group MAD and the control group. CONCLUSION: The NF-κB pathway was activated in the myocardium of OSA rabbits, which accelerated the development of MF. Early application of MAD could reduce the activation of NF-κB in the myocardium and prevent the development of MF.

ß,ß-Dimethylacrylalkannin, a Natural Naphthoquinone, Inhibits the Growth of Hepatocellular Carcinoma Cells by Modulating Tumor-Associated Macrophages.

Tumor-associated macrophages (TAMs) are pivotal in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC), influencing various stages from initiation to metastasis. Understanding the role of TAMs in HCC is crucial for developing novel therapeutic strategies. Macrophages exhibit plasticity, resulting in M1 and M2 phenotypes, with M1 macrophages displaying antitumor properties and M2 macrophages promoting tumor progression. Targeting TAMs to alter their polarization could offer new avenues for HCC treatment. ß,ß-dimethylacrylalkannin (DMAKN), a natural naphthoquinone, has gained attention for its antitumor properties. However, its impact on TAMs modulation remains unclear. This study investigates DMAKN's modulation of TAMs and its anti-HCC activity. Using an in vitro model with THP-1 cells, we induced M1 macrophages with LPS/IFN-γ and M2 macrophages with IL-4/IL-13, confirming polarization with specific markers. Co-culturing these macrophages with HCC cells showed that M1 cells inhibited HCC growth, while M2 cells promoted it. Screening for non-toxic DMAKN concentrations revealed its ability to induce M1 polarization and enhance LPS/IFN-γ-induced M1 macrophages, both showing anti-HCC effects. Conversely, DMAKN suppressed IL-4/IL-13-induced M2 polarization, inhibiting M2 macrophages' promotion of HCC cell viability. In summary, DMAKN induces and enhances M1 polarization while inhibiting M2 polarization of macrophages, thereby inhibiting HCC cell growth. These findings suggest that DMAKN has the potential to regulate TAMs in HCC, offering promise for future therapeutic development.

The role of cannabinoid receptor 2 in bone remodeling during orthodontic tooth movement.

BACKGROUND: The purpose of this study is to explore the effects of CB2 on bone regulation during orthodontic tooth movement. METHODS: Thirty male mice were allocated into 2 groups (n = 15 in each group): wild type (WT) group and CB2 knockout (CB2-/-) group. Orthodontic tooth movement (OTM) was induced by applying a nickel-titanium coil spring between the maxillary first molar and the central incisors. There are three subgroups within the WT groups (0, 7 and 14 days) and the CB2-/- groups (0, 7 and 14 days). 0-day groups without force application. Tooth displacement, alveolar bone mass and alveolar bone volume were assessed by micro-CT on 0, 7 and 14 days, and the number of osteoclasts was quantified by tartrate-resistant acid phosphatase (TRAP) staining. Moreover, the expression levels of RANKL and OPG in the compression area were measured histomorphometrically. RESULTS: The WT group exhibited the typical pattern of OTM, characterized by narrowed periodontal space and bone resorption on the compression area. In contrast, the accelerated tooth displacement, increased osteoclast number (P < 0.0001) and bone resorption on the compression area in CB2-/- group. Additionally, the expression of RANKL was significantly upregulated, while OPG showed low levels in the compression area of the CB2 - / - group (P < 0.0001). CONCLUSIONS: CB2 modulated OTM and bone remodeling through regulating osteoclast activity and RANKL/OPG balance.

Nitrogen-doped titanium dioxide/schwertmannite nanocomposites as heterogeneous photo-Fenton catalysts with enhanced efficiency for the degradation of bisphenol A.

Potential health risks related to environmental endocrine disruptors (EEDs) have aroused research hotspots at the forefront of water treatment technologies. Herein, nitrogen-doped titanium dioxide/schwertmannite nanocomposites (N-TiO2/SCH) have been successfully developed as heterogeneous catalysts for the degradation of typical EEDs via photo-Fenton processes. Due to the sustainable Fe(III)/Fe(II) conversion induced by photoelectrons, as-prepared N-TiO2/SCH nanocomposites exhibit much enhanced efficiency for the degradation of bisphenol A (BPA; ca. 100% within 60 min under visible irradiation) in a wide pH range of 3.0-7.8, which is significantly higher than that of the pristine schwertmannite (ca. 74.5%) or N-TiO2 (ca. 10.8%). In this photo-Fenton system, the efficient degradation of BPA is mainly attributed to the oxidation by hydroxyl radical (•OH) and singlet oxygen (1O2). Moreover, the possible catalytic mechanisms and reaction pathway of BPA degradation are systematically investigated based on analytical and photoelectrochemical analyses. This work not only provides a feasible means for the development of novel heterogeneous photo-Fenton catalysts, but also lays a theoretical foundation for the potential application of mineral-based materials in wastewater treatment.

Dietary astaxanthin: an excellent carotenoid with multiple health benefits.

Astaxanthin is a carotenoid widely found in marine organisms and microorganisms. With extensive use in nutraceuticals, cosmetics, and animal feed, astaxanthin will have the largest share in the global market for carotenoids in the near future. Owing to its unique molecular features, astaxanthin has excellent antioxidant activity and holds promise for use in biochemical studies. This review focuses on the observed health benefits of dietary astaxanthin, as well as its underlying bioactivity mechanisms. Recent studies have increased our understanding of the role of isomerization and esterification in the structure-function relationship of dietary astaxanthin. Gut microbiota may involve the fate of astaxanthin during digestion and absorption; thus, further knowledge is needed to establish accurate recommendations for dietary intake of both healthy and special populations. Associated with the regulation of redox balance and multiple biological mechanisms, astaxanthin is proposed to affect oxidative stress, inflammation, cell death, and lipid metabolism in humans, thus exerting benefits for skin condition, eye health, cardiovascular system, neurological function, exercise performance, and immune response. Additionally, preclinical trials predict its potential effects such as intestinal flora regulation and anti-diabetic activity. Therefore, astaxanthin is worthy of further investigation for boosting human health, and wide applications in the food industry.

In-Depth Analysis of the Mechanism of Astaxanthin Succinate Diester in Reducing Ulcerative Colitis in C57BL/6J Mice Based on Microbiota Informatics.

This paper aims to explore the effect and mechanism of water-soluble astaxanthin succinate diester (Asta-SD) on ulcerative colitis (UC) induced by dextran sodium sulfate in zebrafish and C57BL/6J mice. Asta-SD was synthesized with hydrophilic fatty acid succinic anhydride and the hydroxyl groups at the ends of F-Asta were synthesized by esterifying. Through the construction of a zebrafish intestinal inflammation model, it was found that Asta-SD could effectively reduce the levels of ROS and increase the number of healthy intestinal lysosomes in zebrafish. After continuous gavage of Asta-SD for seven days, the body weight, disease activity index, colonic length, colonic histopathology, expression of inflammatory factors, and intestinal flora of the mice were measured. The results showed that Asta-SD could significantly alleviate weight loss and colonic shrinkage, as well as reducing pro-inflammatory cytokines and recess injury in UC mice. The 16S rRNA gene sequencing showed that Asta-SD significantly increased the beneficial bacteria (Lactobacillus, Anaerotruncus) and decreased the relative abundance of pathogenic bacteria, effectively maintaining intestinal microbiota homeostasis in mice. Based on Pearson analysis, Bacteroides, Parabacteroides, and Butyrimionas were expected to be associated with the significant difference in the expression of inflammatory factors between the UC and the corresponding host. Thus, Asta-SD significantly improves UC and maintains intestinal microbiota homeostasis.

Stability and bioavailability of protein matrix-encapsulated astaxanthin ester microcapsules.

BACKGROUND: Astaxanthin ester derived from Haematococcus pluvialis is often used as a functional and nutritional ingredient in foods. However, its utilization is currently limited as a result of its chemical instability and low bioavailability. Food matrix microcapsules are becoming increasingly popular because of their safety and high encapsulation efficiency. In the present study, the effect of protein matrixes on the properties of microcapsules was evaluated. RESULTS: We investigated the effects of storage on astaxanthin ester microcapsules and the corresponding rehydration solution at 40 °C under a nitrogen atmosphere, as well as in darkness. The results showed that the stability of products prepared based on whey protein (WP) and corn-gluten was superior to that of products prepared based on lactoferrin, soy protein and sodium caseinate. The bioavailability of astaxanthin ester microcapsules encapsulated with different proteins and examined by means of astaxanthin concentrations in the serum and liver after oral administration was compared. All five protein wall materials could significantly improve the bioavailability of astaxanthin ester. The microcapsules prepared based on WP had the highest bioavailability, with a value of 10.69 ± 0.75 µg·h mL-1 , which was 3.15 times higher compared to that of the control group. CONCLUSION: The results of the present study showed that protein encapsulation, especially WP encapsulation, could effectively improve the stability, water solubility and bioavailability of astaxanthin esters. Thus, WP can be used as the main wall material in delivery systems. © 2021 Society of Chemical Industry.

Effects of microencapsulation in dairy matrix on the quality characteristics and bioavailability of docosahexaenoic acid astaxanthin.

BACKGROUND: Compared with free astaxanthin (Asta), docosahexaenoic acid astaxanthin monoester (Asta-C22:6) has higher stability and bioavailability. However, Asta-E is still unable to be used in the water system. Hence it is necessary to build a water-soluble delivery system. In this study, Asta-C22:6 microemulsion and microcapsule using whey protein isolate (WPI) and hydroxypropyl-ß-cyclodextrin (HPß-CD) as composite wall material were prepared. They were added to three dairy products (milk powder, yogurt and flavored dairy product). A dairy product rich in Asta-C22:6 with high bioavailability was designed by measuring quality characteristics, sensory evaluation and in vivo experiments. RESULTS: Compared with spray drying, the freeze-drying microcapsule had a higher encapsulation efficiency (72.5%), water content (4%) and better solubility, and Asta-C22:6 microcapsule (1 g L-1 ) yogurt had the best quality. The bioavailability of Asta-C22:6 microcapsule yogurt was further evaluated. After a single oral dose in mice, the bioavailability of Asta-C22:6 microcapsule in yogurt was significantly increased (Cmax  = 0.31 µg mL-1 , AUC0-T  = 3.20 h µg mL-1 ). CONCLUSION: We successfully prepared Asta-C22:6 microcapsule yogurt, which improved the stability and bioavailability of Asta. The present research is meaningful for delivering unstable bioactive small molecules based on WPI and HPß-CD. It provides an experimental basis for the application of Asta-C22:6 and the development of functional dairy products. © 2022 Society of Chemical Industry.

Influence of oil matrixes on stability, antioxidant activity, bioaccessibility and bioavailability of astaxanthin ester.

BACKGROUND: Astaxanthin ester (Asta-E) is used as functional nutraceuticals in many food products. Unfortunately, Asta-E utilization is currently limited owing to its chemical instability and low bioavailability. The purpose of this study is to investigate the promotion effect of oil matrixes on the stability, antioxidant activity, bioaccessibility and bioavailability of Asta-E. RESULTS: The results showed that the stability of Asta-E in six oil matrixes was improved. Based on the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity experiment, the antioxidant activity of Asta-E was positively correlated with the degree of unsaturation of the oil matrixes, but not with the side chain length. The in vitro gastrointestinal tract (GIT) simulation model and in vivo experiment using mice were also employed to investigate the digestion and absorption characteristics of Asta-E in various oil matrixes. The results demonstrated that the bioaccessibility and bioavailability of Asta-E increased with the increase of fatty acid chain length of oil matrixes (triglyceride oleate > triglyceride caprylate > triglyceride butyrate), as well as with the decrease of unsaturation degree (olive oil > corn oil > fish oil). CONCLUSION: Monounsaturated fatty acids (MUFA) and long-chain triglyceride (LCT) in an oil matrix were the factors that could efficiently improve the bioavailability of Asta-E. Moreover, the size of the mixed micelles of Asta-E during digestion was the main factor influencing the bioaccessibility of Asta-E. This study provides references for the design of suitable oil matrixes for Asta-E. © 2020 Society of Chemical Industry.

Preparation, characterization and antioxidant activity of astaxanthin esters with different molecular structures.

BACKGROUND: Astaxanthin (Asta) is widely used in the nutraceutical and food industry because of its strong antioxidant properties. However, natural Asta mainly exists in the esterified form with various fatty acid chains, making it difficult to understand the particular molecular structure of astaxanthin esters (Asta-Es) that have better antioxidant capacity. In this study, Asta-Es with different molecular structures was systematically prepared, and identified by using thin-layer chromatography (TLC), ultraviolet-visible (UV-visible), high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and proton nuclear magnetic resonance (1 H-NMR). In addition, their antioxidant properties were evaluated by 2,2'-diphenylpicrylhydrazyl (DPPH) and ABTS scavenging activity. RESULTS: Fourteen Asta-Es with different molecular structures were systematically synthesized. This study used a simple and efficient method for the separation and purification of astaxanthin monoester (Asta-ME) and astaxanthin diester (Asta-DE) with high purity (86%-94%) by silica gel column chromatography. 13-cis-Asta-E and 9-cis-Asta-E were firstly identified from Asta-E. The DPPH clearance rates and ABTS scavenging rates of Asta-C4:0, Asta-C8:0, Asta-C12:0, and Asta-C18:0 were relatively close, but the DPPH and ABTS scavenging rates of Asta-C18:0, Asta-C18:1, Asta-C18:2, and Asta-C22:6 increased gradually. Among all Asta-Es, Asta-C22:6/C22:6 showed the highest antioxidant capacity, with the DPPH and ABTS scavenging rates of 77.22 ± 3.29% and 51.84 ± 1.65%, respectively. CONCLUSION: In this study, it was concluded that chemically synthesized Asta-Es contained cis-astaxanthin ester and polyunsaturated fatty acid chain increased the antioxidant activity of Asta, showing less effect of the length of fatty acid chain. These results provide useful information for the production and use of highly efficient Asta-E as functional food and pharmaceutical ingredients. © 2020 Society of Chemical Industry.

Three-dimensional changes of the upper airway in patients with Class II malocclusion treated with functional appliances: a systematic review and meta-analysis.

BACKGROUND/OBJECTIVE: To evaluate the three-dimensional (3D) changes of the upper airway in patients with Class II malocclusion treated with functional appliances (FAs). SEARCH METHODS AND ELIGIBILITY CRITERIA: A comprehensive search of seven electronic databases was conducted from the date of inception to 12 July 2020. Manual search was also performed in relevant Chinese and English periodicals. Prospective and retrospective studies evaluating the 3D airway changes after FAs applied on growing patients with skeletal Class II malocclusion were included. DATA COLLECTION AND ANALYSIS: Risk of bias assessment of each included study was performed referring to ROBINS-I. The effects of FAs on upper airway were evaluated by meta-analysis using STATA software. The outcome variables were the changes of oropharyngeal airway volumes (OAVs), nasopharyngeal airway volumes (NAVs), minimum cross-sectional area (MCA) and antero-posterior position of hyoid bone (HB). The overall quality of evidence for each outcome was rated based on Grading of Recommendations Assessment, Development and Evaluation recommendations. RESULTS: Nine studies were ultimately included in the systematic review and five were included and analyzed in meta-analysis. The results indicated that the pooled mean differences among these studies were 2162.80 [95 per cent confidence interval (CI): 1264.97, 3060.62), 382.20 (95 per cent CI: 140.95, 623.44), 59.91 (95 per cent CI: 41.45, 78.38), and 0.63 (95 per cent CI: -1.97, 3.23) for changes of OAVs, NAVs, MCA, and antero-posterior position of HB, respectively. CONCLUSION: Weak evidence suggests that FAs can increase OAVs, NAVs, and MCA in growing patients with Class II malocclusion. Weak evidence also suggests that antero-posterior position of HB cannot be affected by FAs. Further studies are necessary to assess the stability of its effect on the upper airway in the long term. REGISTRATION: The review protocol was not registered prior to the study.

Effect of Nitrate Ions on Acidithiobacillus ferrooxidans-Mediated Bio-oxidation of Ferrous Ions and Pyrite.

Exploring the effects of nitrate ions (NO3-) on the bio-oxidation of Fe2+ and pyrite will help reveal the actual mechanism of acid mine drainage (AMD) production. Long period shaking flask experiments were carried out in order to assess the effect of NO3- on the Acidithiobacillus ferrooxidans LX5 (A. ferrooxidans LX5)-mediated bio-oxidation of Fe2+ and pyrite. In Fe2+ bio-oxidation systems, A. ferrooxidans LX5 had stronger Fe2+ oxidation capabilities in a NO3--loaded solution than in a NO3--free solution after 24 days, and the Fe2+ bio-oxidation capacity of A. ferrooxidans LX5 acclimatized in solutions containing low concentrations (8.2-32.9 mmol/L) of NO3- was greater than when it was acclimatized in high NO3- concentration solutions (49.4-65.8 mmol/L). In pyrite bio-oxidation systems, in comparison with the system without NO3-, pyrite bio-oxidation efficiency was significantly increased when the NO3- concentration in the system was 8.2-16.5 mmol/L, and that the pyrite bio-oxidation efficiency in the system containing 8.2 mmol/L of NO3- was greater than that for the system with 16.5 mmol/L of NO3-. The pyrite bio-oxidation efficiency was inhibited when the NO3- concentration was above 32.9 mmol/L. The results from this study can be used to reveal the actual control behavior of NO3- on AMD production.

Oxidation evaluation of free astaxanthin and astaxanthin esters in Pacific white shrimp during iced storage and frozen storage.

BACKGROUND: In this paper, the changes in free astaxanthin (F-AST) and astaxanthin esters (AST-Es) in Litopenaeus vannamei during iced storage and frozen storage were investigated. The liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry method was used to quantify the molecular species of AST-Es in shrimp during storage. RESULTS: Based on the analysis of autoxidation products, apo-12-astaxanthinal and apo-13-astaxanthinone docosahexaenoic acid (DHA) ester were identified as the major oxidation products of F-AST and AST-Es in L. vannamei during storage. The total astaxanthin (T-AST) content decreased by 34.51% after 7 days in iced storage. In contrast, the content of T-AST decreased by 43.76% after 12 weeks in frozen storage. The content of F-AST decreased by 29.99% while 13-cis-astaxanthin increased after 3 days in iced storage, which indicated that degradation of AST was accompanied by isomerization. Total volatile basic nitrogen and T-AST content showed a significant negative correlation while in frozen storage, where the concentration of T-AST might be one indicator to evaluate shrimp freshness. CONCLUSION: The correlation coefficients between phenol oxidase, lipoxygenase, apo-12-astaxanthinal, and apo-13-astaxanthinone DHA ester were all greater than 0.97 (P < 0.01). This correlation indicates that phenol oxidase and lipoxygenase were the main internal factors to improve oxygenation of astaxanthin in L. vannamei. These results provide a theoretical basis for further study of oxidation and the degradation mechanism in astaxanthin, as well as a new idea for the development and utilization of astaxanthin compounds in Pacific white shrimp. © 2018 Society of Chemical Industry.

Synthesis, stability and bioavailability of astaxanthin succinate diester.

BACKGROUND: We synthesized astaxanthin succinate diester (ASD), a novel astaxanthin (AST) derivate, with succinic anhydride and free AST. ASD was purified and characterized using silica gel column chromatography and spectrometry, respectively. RESULTS: The ASD final synthesis rate was 82.63%. A stability test revealed a high AST and ASD retention rate at pH 5.0-7.0. ASD showed better stability than did AST under acidic conditions. Both sample ions showed lower retention rates under Fe2+ and Fe3+ states. The ASD metabolic curve showed serum and liver area under the curve from 0 h to time t (AUC0-t ) values of 45.05 ± 4.58 and 120.38 ± 23.66 µg h-1  mL-1 , respectively. The long-term accumulation was significantly higher in the ASD group than in the AST group, which showed higher accumulation in the heart, muscle and spleen than in other tissues in vivo. CONCLUSION: The thermal stability and bioavailability of ASD were higher than that of the non-esterified free AST and common free AST, respectively. Additionally, AST accumulation in different tissues of the ASD group was multifold higher than that of free AST. These results prove that ASD may serve as a better source of AST for human nutrition than does free AST. © 2017 Society of Chemical Industry.

Synthesis of lipophilic antioxidant tyrosol laurate using imidazolium ionic liquid [Bmim]HSO4 as a catalyst.

Tyrosol is a natural phenolic compound with potent antioxidant properties in the field of food manufacturing. However, the low lipophilicity of tyrosol limited its application. Therefore, the construction of tyrosol laurate (Tyr-L) could effectively overcome the limitations of tyrosol. In this work, four ionic liquids (ILs) were applied for TYr-L preparation. Among them, the 1-butyl-3-methylimidazolium hydrogen sulfate ([Bmim]HSO4) showed the best catalytic performance. The maximum TYr-L yield was achieved (94.24 ± 1.23 %) under the optimal conditions (reaction temperature 119 °C, substrate ratio 1:6.7, IL dosage 9.2 %, and reaction time 12 h). The kinetic and thermodynamic parameters were also evaluated and it was found that Ea, ΔH, ΔS, and ΔG were 80.81 kJ·mol-1, 77.63 kJ·mol-1, -82.08 J·(mol·K)-1, and 109.89 kJ·mol-1, respectively. The acidic [Bmim]HSO4 demonstrated excellent reusability and stability, even after 6 cycles. Furthermore, TYr-L showed superior ABTS radical scavenging ability, which could be further applied in various industrial processes.

[Effects of Biochar on Growth and Pollutant Accumulation of Lettuce in Soil Co-contaminated with Tetracycline and Copper].

Through lettuce potting experiments, the effects of different types of biochar (apple branch, corn straw, and modified sorghum straw biochar with phosphoric acid modification) on lettuce growth under tetracycline (TC) and copper (Cu) co-pollution were investigated. The results showed that compared with those under CK, the addition of biochar treatment significantly increased the plant height, root length, shoot fresh weight, and root fresh weight of lettuce (P < 0.05). The addition of different biochars significantly increased the nitrate nitrogen, chlorophyll, and soluble protein content in lettuce physiological indicators to varying degrees, while also significantly decreasing the levels of malondialdehyde, proline content, and catalase activity. The effects of biochar on lettuce physiological indicators were consistent during both the seedling and mature stages. Compared with those in CK, the addition of biochar resulted in varying degrees of reduction in the TC and Cu contents of both the aboveground and underground parts of lettuce. The aboveground TC and Cu levels decreased by 2.49%-92.32% and 12.79%-36.47%, respectively. The underground TC and Cu levels decreased by 12.53%-55.64% and 22.41%-42.29%, respectively. Correlation analysis showed that nitrate nitrogen, chlorophyll, and soluble protein content of lettuce were negatively correlated with TC content, whereas malondialdehyde, proline content, and catalase activity were positively correlated with TC content. The resistance genes of lettuce were positively correlated with TC content (P < 0.05). In general, modified biochar was found to be more effective in improving lettuce growth quality and reducing pollutant accumulation compared to unmodified biochar, with modified sorghum straw biochar showing the best remediation effect.

ß,ß-Dimethylacrylalkannin, a key component of Zicao, induces cell cycle arrest and necrosis in hepatocellular carcinoma cells.

BACKGROUND: ß,ß-Dimethylacrylalkannin (DMAKN), a natural naphthoquinone found in Zicao, a traditional Chinese medicine (TCM), serves as the designated quantitative marker in the Chinese Pharmacopoeia. Despite its established role in assessing Zicao quality, DMAKN's biological potential remains underexplored in research. METHODS: We investigated DMAKN's involvement in Zicao's anti-hepatocellular carcinoma (HCC) properties using a combination of HPLC content analysis and comprehensive bioinformatics. Subsequently, both in vitro and in vivo experiments were conducted to evaluate DMAKN's efficacy against HCC. Mechanistic investigations focused on elucidating DMAKN's impact on cell cycle regulation and induction of cell death. RESULTS: Integrated HPLC analysis and bioinformatics identified DMAKN as the primary active compound responsible for Zicao's anti-HCC activity. In vitro and in vivo studies confirmed DMAKN's potent efficacy against HCC. Notably, DMAKN demonstrated dual effects on HCC cells: inhibiting proliferation at lower doses and inducing rapid cell death at higher doses. Mechanistic insights revealed that low-dose DMAKN induced G2/M phase cell cycle arrest through modulation of CDK1 and Cdc25C phosphorylation, while high-dose DMAKN triggered necrosis. Importantly, high-dose DMAKN caused a sharp increase in intracellular ROS levels in a short time, while low-dose DMAKN gradually increased ROS levels over a long period. Additionally, low-dose DMAKN-induced ROS activated the JNK pathway, crucial for cell cycle arrest, whereas high-dose DMAKN-induced necrosis was ROS-dependent but JNK-independent. CONCLUSION: This study underscores DMAKN's pivotal role as the principal anti-HCC compound in Zicao, delineating its differential effects and underlying mechanisms. These results demonstrate the potential of DMAKN as a therapeutic agent for the treatment of HCC, providing important information for further study and advancement in cancer therapy.

Characterization of Prototheca zopfii associated with outbreak of bovine clinical mastitis in herd of Beijing, China.

Prototheca zopfii (P. zopfii) has become an important cause of bovine mastitis in many countries. In the present study, to better understand the occurrence of one clinical mastitis (CM) outbreak due to P. zopfii, the molecular characterization and resistance patterns of the microalga were described. P. zopfii strains were isolated from 17 of 23 quarters, which suffered CM in the outbreak, and 7 of 46 CM recovered quarters before the outbreak, as well as 2 of 75 environmental samples in the dairy farm. All strains were identified as genotype 2 by genotype-specific PCR analysis. Results of in vitro antimicrobial and antifungal susceptibility tests indicated that these strains were resistant to majority of tested drugs, with the only exception of amphotericin B, nystatin, streptomycin, gentamicin, and amikacin. This is the first report about CM outbreak caused by P. zopfii in China. These data suggest that P. zopfii may represent a serious risk in the studied herd, and this microalga could be an important potential pathogen causing mastitis in dairy herds of Beijing.

Adipose-derived stem cells accelerate neovascularization in ischaemic diabetic skin flap via expression of hypoxia-inducible factor-1α.

Skin flaps are frequently performed for diabetic patients in spite of countless detrimental effects of diabetes on flap survival, most of which may result from a defective response of the tissues to low oxygen tension. In this study, the authors explored the feasibility of applying human adipose-derived stem cells (ASCs) to increase the viability of random-patterned skin flaps in streptozotocin-induced diabetic mice. ASCs were isolated from the fresh human lipoaspirates and expanded ex vivo for three passages. After the elevation of caudally based random-patterned skin flaps (3 cm long and 1 cm wide), ASCs suspensions were then injected into the flap (group A). Media containing no ASCs were similarly injected as a control (group B), although nothing was injected into the flap base of mice in control group C. Flap assessments were carried out at post-operative day 7 for evaluation of flap viability. The flap survival rate of group A was significantly higher than those of groups B and C, whereas no difference was observed between groups B and C. Histological examination also demonstrated a statistically significant increase in capillary density in group A over both groups B and C. Furthermore, it was found that ASCs not only augmented the expression of vascular endothelial growth factor and hypoxia-inducible factor-1α (HIF-1α) in flap tissues from dermis of diabetes mice, but also promoted their expression in dermal fibroblasts from diabetic mice. Thus, ASCs could enhance the survival of random-patterned skin flaps in streptozotocin-induced diabetic mice via elevated expression of HIF-1α.

Targeting galectins in T cell-based immunotherapy within tumor microenvironment.

Over the past few years, tumor immunotherapy has emerged as an innovative tumor treatment and owned incomparable advantages over other tumor therapy. With unique complexity and uncertainty, immunotherapy still need helper to apply in the clinic. Galectins, modulated in tumor microenvironment, can regulate the disorders of innate and adaptive immune system resisting tumor growth. Considering the role of galectins in tumor immunosuppression, combination therapy of targeted anti-galectins and immunotherapy may be a promising tumor treatment. This brief review summarizes the expression and immune functions of different galectins in tumor microenvironment and discusses the potential value of anti-galectins in combination with checkpoint inhibitors in tumor immunotherapy.