Consumption Patterns of Sugar-Sweetened Beverages and Association with Undernutrition among Children Aged 9-17 Years in Guangzhou, China: A Cross-Sectional Study.

Globally, the high consumption levels of sugar-sweetened beverages (SSBs) and their effect on health have drawn significant attention. This study aimed to identify the consumption patterns of SSBs among children in rural areas of Guangzhou, China, and explore their association with undernutrition. A total of 1864 children aged 9-17 years old were included in this study. Demographics, lifestyle behaviors, and anthropometric and dietary information were collected. Factor analysis was used to identify patterns of SSBs, while nutritional status was assessed using Body Mass Index (BMI). Latent class analysis was used to establish dietary preference models. Log-binomial regression analysis was used to analyze the association between SSBs consumption patterns and undernutrition. The undernutrition prevalence in children was 14.54-19.94% in boys and 9.07% in girls. Three SSB consumption patterns were identified, including the plant protein pattern, dairy-containing pattern, and coffee pattern. Both medium-high (Q3) and the highest (Q4) scores in the dairy-containing pattern were positively associated with the risk of undernutrition, especially in boys. Furthermore, the highest scores in the plant protein pattern and coffee pattern were positively associated with the risk of undernutrition in children aged 9-10 years old. The dairy-containing pattern was a risk factor for undernutrition in children, especially for boys; the plant protein patterns and coffee patterns were risk factors for undernutrition in children aged 9-10 years old. The findings of the study can provide scientific evidence and policy recommendations for improving children's health conditions.

Essential oil from Citrus depressa peel exhibits antimicrobial, antioxidant and cancer chemopreventive effects.

BACKGROUND: Many diseases may be caused by pathogens and oxidative stress resulting from carcinogens. Earlier studies have highlighted the antimicrobial and antioxidant effects of plant essential oils (EO). It is crucial to effectively utilize agricultural waste to achieve a sustainable agricultural economy and protect the environment. The present study aimed to evaluate the potential benefits of EO extracted from the discarded peels of Citrus depressa Hayata (CD) and Citrus microcarpa Bunge (CM), synonyms of Citrus deliciosa Ten and Citrus japonica Thunb, respectively. RESULTS: Gas chromatography-mass spectrometry analysis revealed that the main compounds in CD-EO were (R)-(+)-limonene (38.97%), γ-terpinene (24.39%) and linalool (6.22%), whereas, in CM-EO, the main compounds were (R)-(+)-limonene (48.00%), ß-pinene (13.60%) and γ-terpinene (12.07%). CD-EO exhibited inhibitory effects on the growth of common microorganisms, including Candida albicans, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. However, CM-EO showed only inhibitory effects on E. coli. Furthermore, CD-EO exhibited superior antioxidant potential, as demonstrated by its ability to eliminate 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azinobis-3-ethylbenzthiazoline-6-sulfonate free radicals. Furthermore, CD-EO at a concentration of 100 µg mL-1 significantly inhibited 12-O-tetradecanoylphorbol-13-acetate-induced cancer transformation in mouse epidermal JB6 P+ cells (P < 0.05), possibly by up-regulating protein expression of nuclear factor erythroid 2-related factor 2 and its downstream antioxidant enzymes, such as NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1 and UGT1A. CONCLUSION: These findings suggest that CD-EO exhibits inhibitory effects on pathogenic microorganisms, possesses antioxidant properties and has cancer chemopreventive potential. © 2024 Society of Chemical Industry.

Chemoprevention of lotus leaf ethanolic extract through epigenetic activation of the NRF2-mediated pathway in murine skin JB6 P+ cell neoplastic transformation.

Background and aim: Skin is one barrier protecting from environmental risk factors that can make skin cells cancerous through DNA damage and oxidative stress. The nuclear factor erythroid 2-related factor 2 (NRF2) pathway is an anti-stress defense system that can be regulated by DNA methylation and histone modification. Dietary phytochemicals have chemopreventive properties that can inhibit or delay carcinogenesis. The lotus leaf is a traditional medicinal plant containing many polyphenols whose extracts show many biological activities, including antioxidant, anti-obesity, and anti-cancer. This study aim to investigate the effect of lotus leaves on neoplastic transformation in murine skin JB6 P+ cells. Experimental procedure: Lotus leaves were extracted with water (LL-WE) and ethanol (LL-EE), and the LL-WE residues were further extracted with ethanol (LL-WREE). JB6 P+ cells were treated with different extracts. The chemoprotective effect would be evaluated by heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase (NQO1), and UDP glucuronosyltransferase family 1 member A1 (UGT1A1) expression. Results and conclusion: LL-EE contained higher total phenolics and quercetin among extracts. In mouse skin JB6 P+ cells with 12-O-tetradecanoylphorbol-13-acetate treatment, LL-EE showed the greatest potential to suppress skin carcinogenesis. LL-EE activated the NRF2 pathway by upregulating antioxidant and detoxification enzymes upregulates antioxidant and detoxification enzymes, including HO-1, NQO1, and UGT1A1, and downregulates DNA methylation, which might be caused by lower DNA methyltransferase and histone deacetylase levels. Therefore, our results show that LL-EE reduces the neoplastic transformation of skin JB6 P+ cells, potentially by activating the NRF2 pathway and regulating epigenetic DNA methylation and histone acetylation.

A Novel Hexokinases Inhibitor Based on Molecularly Imprinted Polymer for Combined Starvation and Enhanced Photothermal Therapy of Malignant Tumors.

The heat tolerance of tumor cells induced by heat shock proteins (HSPs) is the major factor that seriously hinders further application of PTT, as it can lead to tumor inflammation, invasion, and even recurrence. Therefore, new strategies to inhibit HSPs expression are essential to improve the antitumor efficacy of PTT. Here, we prepared a novel nanoparticle inhibitor by synthesizing molecularly imprinted polymers with a high imprinting factor (3.1) on the Prussian Blue surface (PB@MIP) for combined tumor starvation and photothermal therapy. Owing to using hexokinase (HK) epitopes as the template, the imprinted polymers could inhibit the catalytic activity of HK to interfere with glucose metabolism by specifically recognizing its active sites and then achieve starvation therapy by restricting ATP supply. Meanwhile, MIP-mediated starvation downregulated the ATP-dependent expression of HSPs and then sensitized tumors to hyperthermia, ultimately improving the therapeutic effect of PTT. As the inhibitory effect of PB@MIP on HK activity, more than 99% of the mice tumors were eliminated by starvation therapy and enhanced PTT.

Biofilm Homeostasis Interference Therapy via 1 O2 -Sensitized Hyperthermia and Immune Microenvironment Re-Rousing for Biofilm-Associated Infections Elimination.

The recurrence of biofilm-associated infections (BAIs) remains high after implant-associated surgery. Biofilms on the implant surface reportedly shelter bacteria from antibiotics and evade innate immune defenses. Moreover, little is currently known about eliminating residual bacteria that can induce biofilm reinfection. Herein, novel "interference-regulation strategy" based on bovine serum albumin-iridium oxide nanoparticles (BIONPs) as biofilm homeostasis interrupter and immunomodulator via singlet oxygen (1 O2 )-sensitized mild hyperthermia for combating BAIs is reported. The catalase-like BIONPs convert abundant H2 O2 inside the biofilm-microenvironment (BME) to sufficient oxygen gas (O2 ), which can efficiently enhance the generation of 1 O2 under near-infrared irradiation. The 1 O2 -induced biofilm homeostasis disturbance (e.g., sigB, groEL, agr-A, icaD, eDNA) can disrupt the sophisticated defense system of biofilm, further enhancing the sensitivity of biofilms to mild hyperthermia. Moreover, the mild hyperthermia-induced bacterial membrane disintegration results in protein leakage and 1 O2 penetration to kill bacteria inside the biofilm. Subsequently, BIONPs-induced immunosuppressive microenvironment re-rousing successfully re-polarizes macrophages to pro-inflammatory M1 phenotype in vivo to devour residual biofilm and prevent biofilm reconstruction. Collectively, this 1 O2 -sensitized mild hyperthermia can yield great refractory BAIs treatment via biofilm homeostasis interference, mild-hyperthermia, and immunotherapy, providing a novel and effective anti-biofilm strategy.

Quantitative evaluation of radon, tobacco use and lung cancer association in an occupational cohort with 27 follow-up years.

BACKGROUND: Occupational radon cohorts provide important information about exposure at residential level, which are difficult to observe prospectively. However, evidence about radon-related lung cancer risks from initial exposure in childhood or interaction between radon and smoking is still limited. METHODS: A total of 6017 tin miners with at least 10 years of underground radon exposure were enrolled beginning in 1992 and followed for up to 27 years. Lung cancer risks were estimated by modeling total and intensity of radon exposure. RESULTS: A total of 933 lung cancer cases occurred in this cohort over 89,092 person-years of follow up. Excess relative risk increased by 0.96% per cumulative working level month (WLM). A unique aspect of this population was the early age at first radon exposure for workers. Results showed that lung cancer risk from initial radon exposure in childhood (<13 years old) was greater than risk when first exposure occurred at later ages (13-17, 18-24, and ≥ 25 years old). Moreover, risk declined with years since last exposure and attained age, but increased with age at last exposure. Importantly, these patterns were stable after adjustment for tobacco use or arsenic exposure. For joint effects of radon and other agents, our results support sub-multiplicative as the most likely model for interaction between radon and tobacco use or arsenic exposure. CONCLUSION: This study highlights the possible importance of radon exposure in childhood in cancer etiology and suggests another potential strategy to mitigate the global lung cancer burden.

Diterpenoid anthraquinones as chemopreventive agents altered microRNA and transcriptome expressions in cancer cells.

OBJECTIVE: Cryptotanshinone (CPT) and dihydrotanshinone (DHT) are diterpenoid anthraquinone compounds extracted from traditional Chinese herbal medicine (TCM). Recent studies have shown that CPT regulates the signal transduction pathways via microRNA (miRNA) alterations. However, few studies have investigated the role of DHT in miRNA alterations affecting cell-signaling pathways. This study aimed to investigate the miRNA alterations and post-transcriptional regulation activities of DHT in comparison to CPT. METHODS: HepG2 and HT-29 cells were treated with DHT or CPT for 72 h. MiRNA, transcription factor encoding mRNA, and downstream gene expression were determined using real-time quantitative PCR. Protein expression was analyzed using western blotting. RESULTS: The results revealed that CPT and DHT targeted cell proliferation and apoptosis signaling pathways via miR-15a-5p, miR-27a-5p, miR-100-5p, and miR-200a-5p alterations.In silico target predictions showed that downregulation of epidermal growth factor receptor (EGFR) mRNA expression by DHT might also suppress the expression of STAT family proteins and lead to anti-proliferation effects. We also found that, compared to CPT, DHT might possess higher potency in cell growth regulation via multi-miRNA and transcription factor alterations. CONCLUSION: This study revealed that CPT and DHT targeted cell proliferation and apoptosis signaling pathways via alterations in miRNAs and transcription factors. In addition, the findings of this study suggest that DHT is more potent than CPT in cancer chemopreventive activities. Therefore, DHT at a low dose is a TCM compound with less toxic side effects and may contribute to the development of natural medicine as a potential cancer chemopreventive agent.

Aged Citrus Peel (Chenpi) Prevents Acetaminophen-Induced Hepatotoxicity by Epigenetically Regulating Nrf2 Pathway.

Excessive consumption of analgesic drug acetaminophen (APAP) can cause severe oxidative stress-mediated liver injury. Here, we investigated the protective effect and mechanism of aged citrus peel (Chenpi, CP), a Chinese herb usually used in foods in Asia, against APAP-induced hepatotoxicity. CP water (CP-WE), ethanolic (CP-EE), and water extraction residue ethanolic (CP-WREE) extracts were prepared. We found that CP-WREE contained higher content of bioactive flavonoids, including narirutin, nobiletin, and tangeretin, and more effectively enhanced the Nrf2 pathway in ARE-luciferase reporter gene transfected human HepG2-C8 cells. In mouse AML-12 hepatocytes, CP-WREE minimized APAP-induced damage and lipid peroxidation and increased mRNA and protein expressions of Nrf2 and its downstream defense enzymes (HO-1, NQO1, and UGT1A). CP-WREE also downregulated HDACs and DNMTs, upregulated KDMs, and increased the unmethylated Nrf2 promoter level. Additionally, CP-WREE blocked in vitro DNA methyltransferase activity. Taken together, CP-WREE might attenuate oxidative stress-induced hepatotoxicity through epigenetically regulating Nrf2-mediated cellular defense system.

Panoramic Visualization of Circulating MicroRNAs Across Neurodegenerative Diseases in Humans.

Neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and dementia pose one of the greatest health challenges this century. Although these NDs have been looked at as single entities, the underlying molecular mechanisms have never been collectively visualized to date. With the advent of high-throughput genomic and proteomic technologies, we now have the opportunity to visualize these diseases in a whole new perspective, which will provide a clear understanding of the primary and secondary events vital in achieving the final resolution of these diseases guiding us to new treatment strategies to possibly treat these diseases together. We created a knowledge base of all microRNAs known to be differentially expressed in various body fluids of ND patients. We then used several bioinformatic methods to understand the functional intersections and differences between AD, PD, ALS, and MS. These results provide a unique panoramic view of possible functional intersections between AD, PD, MS, and ALS at the level of microRNA and their cognate genes and pathways, along with the entities that unify and separate them. While the microRNA signatures were apparent for each ND, the unique observation in our study was that hsa-miR-30b-5p overlapped between all four NDS, and has significant functional roles described across NDs. Furthermore, our results also show the evidence of functional convergence of miRNAs which was associated with the regulation of their cognate genes represented in pathways that included fatty acid synthesis and metabolism, ECM receptor interactions, prion diseases, and several signaling pathways critical to neuron differentiation and survival, underpinning their relevance in NDs. Envisioning this group of NDs together has allowed us to propose new ways of utilizing circulating miRNAs as biomarkers  and in visualizing diverse NDs more holistically . The critical molecular insights gained through the discovery of ND-associated miRNAs, overlapping miRNAs, and the functional convergence of microRNAs on vital pathways strongly implicated in neurodegenerative processes can prove immensely valuable in the identifying new generation of biomarkers, along with the development of miRNAs into therapeutics.

Nano-selenium attenuates nickel-induced testosterone synthesis disturbance through inhibition of MAPK pathways in Sprague-Dawley rats.

The aim of this study was to investigate the protective effects of Nano-Se against Ni-induced testosterone synthesis disorder in rats and determine the underlying protective mechanism. Sprague-Dawley rats were co-treated with Ni (5.0 mg/kg, i.p.) and Nano-Se (0.5, 1.0, and 2.0 mg/kg, oral gavage) for 14 days after which various endpoints were evaluated. The Ni-induced abnormal pathological changes and elevated 8-OHdG levels in the testes were attenuated by Nano-Se administration. Importantly, decreased serum testosterone levels in the Ni-treated rats were significantly restored by Nano-Se treatment, particularly at 1.0 and 2.0 mg/kg. Furthermore, the mRNA and protein levels of testosterone synthetase were increased by Nano-Se compared to the Ni group, whereas phosphorylated protein expression levels of mitogen-activated protein kinase (MAPK) pathways were suppressed by Nano-Se administration in the Ni-treated rats. Overall, the results suggest that Nano-Se may ameliorate the Ni-induced testosterone synthesis disturbance via the inhibition of ERK1/2, p38, and JNK MAPK pathways.

(-)-7(S)-hydroxymatairesinol protects against tumor necrosis factor-α-mediated inflammation response in endothelial cells by blocking the MAPK/NF-κB and activating Nrf2/HO-1.

BACKGROUND: Endothelial inflammation is an increasingly prevalent condition in the pathogenesis of many cardiovascular diseases. (-)-7(S)-hydroxymatairesinol (7-HMR), a naturally occurring plant lignan, possesses both antioxidant and anti-cancer properties and therefore would be a good strategy to suppress tumor necrosis factor-α (TNF-α)-mediated inflammation in vascular endothelial cells (VECs). PURPOSE: The objective of this study is to evaluate for its anti-inflammatory effect on TNF-α-stimulated VECs and underling mechanisms. STUDY DESIGN/METHODS: The effect of the 7-HMR on suppression of TNF-α-induced inflammation mediators in VECs were determined by qRT-PCR and Western blot. MAPKs and phosphorylation of Akt, HO-1 and NF-κB p65 were examined using Western blot. Nuclear localisation of NF-κB was also examined using Western blot and immunofluorescence. RESULTS: Here we found that 7-HMR could suppress TNF-α-induced inflammatory mediators, such as vascularcelladhesion molecule-1, interleukin-6 and inducible nitric oxide synthase expression both in mRNA and protein levels, and concentration-dependently attenuated reactive oxidase species generation. We further identified that 7-HMR remarkably induced superoxide dismutase and heme oxygenase-1 expression associated with degradation of Kelch-like ECH-associated protein 1 (keap1) and up-regulated nuclear factor erythroid 2-related factor 2 (Nrf2). In addition, 7-HMR time- and concentration-dependently attenuated TNF-α-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK) and Akt, but not p38, or c-Jun N-terminal kinase 1/2. Moreover, 7-HMR significantly suppressed TNF-α-mediated nuclear factor-κB (NF-κB) activation by inhibiting phosphorylation and nuclear translocation of NF-κB p65. CONCLUSION: Our results demonstrated that 7-HMR inhibited TNF-α-stimulated endothelial inflammation, at least in part, through inhibition of NF-κB activation and upregulation of Nrf2-antioxidant response element signaling pathway, suggesting 7-HMR might be used as a promising vascular protective drug.

A safety and effectiveness research of Yinhua Pinggan granule of Qingjie Xuantou lung defense prescription for treatment of patients with upper respiratory tract infection accompanied by syndrome of pathogen stagnated in lung-defense phase: a randomized double blinded, positive drug parallel controlled and multicentric clinical trial / 中国中西医结合急救杂志

Objective To evaluate the safety and efficacy of Yinhua Pinggan granule of Qingjie Xuantou lung defense prescription in the treatment of patients with upper respiratory tract infection accompanied by traditional Chinese medicine (TCM) syndrome of pathogen stagnated in lung-defense phase and to explore the best effective dose.Methods A randomized double blinded, positive drug parallel controlled and multicentric clinical trial was conducted, 270 patients with upper respiratory infection were collected from the First Affiliated Hospital of Zhejiang Chinese Medical University, Affiliated Hospital of Jiangxi Medical University, the Second Affiliated Hospital of Tianjin University of TCM, Tongde Hospital of Zhejiang Province, and Fujian Province Institute of TCM, after screening only 242 cases were consistent with the criteria of enrollment into the Per-Protocol Set (PPS) population, and they were divided into three groups: high dose observation group (82 cases), low dose observation group (79 cases) and control group (81 cases). The high and low dose observation groups were treated with Yinhua Pinggan granule (5 g per bag), high dose means once 1 bag orally taken 3 times a day, low dose indicates once 1 bag taken twice a day; the control group was treated with Yinqiao Jiedu granule (5 g per bag) once 1 bag, 3 times a day; the curative effects of the above groups were all evaluated after consecutive oral administration of the drug respectively for 1 therapeutic course (3 days). The main efficacy evaluation indexes included the TCM syndrome total score and the total score of main symptoms of upper respiratory tract infection; the secondary efficacy evaluation indexes included the situations of patients with different scores of main symptoms of fever and chills, and of disappearance of TCM symptoms; the clinical comprehensive therapeutic effect and the changes of proportion of neutrophils were observed and the safety of drugs was evaluated.Results In PPS population, after treatment the TCM syndrome total score and the total score of main symptoms in the control group and the high and low dose observation groups were all significantly lower than those before treatment, on the 3rd day statistical significant differences were shown (4.4±3.9 vs. 15.5±4.6, 3.7±3.2 vs. 15.0±4.3, 3.0±2.7 vs. 15.2±3.9, 2.8±2.6 vs. 9.7±2.7, 2.3±2.1 vs. 9.5±2.5, 2.0±1.9 vs. 9.6±2.4, respectively, all P < 0.01). After treatment for 1 day, the numbers of patients with 6 score in the control group and the high and low dose observation groups were reduced significantly compared with those before treatment in main symptoms of fever with chills (7 vs. 32 cases, 6 vs. 31 cases, 4 vs. 28 cases, respectively); 3 days after treatment, compared with those before treatment, the numbers of patients with main symptoms of fever with chills score being 0 were significantly increased in the above three groups (65, 73, 77 cases vs. 0 cases, respectively), the numbers of patients with the score being 3 were significantly decreased (16 vs. 47 cases, 5 vs. 46 cases, 5 vs. 52 cases, respectively); the control and high dose observation group had no patients with the score being 6, there was only 1 case with the score being 6 in the low dose observation group. The results showed that the treatments of high and low dose observation groups and the control group all could alleviate the clinical symptoms, and the changes of numbers of patients with the scoresbeing 0 and 3 in high and low dose groups were more significant than those in the control group (respectively 73, 77 vs. 65 cases, 5, 5 vs. 16 cases, allP < 0.05), showing that the antipyretic effect of Yinhua Pinggan granule was superior to that of the Yinqiao Jiedu granule. The disappearance rates of fever with chills symptoms in high and low dose observation groups were significantly higher than that in the control group [respectively 93.9% (77/82), 92.4% (73/79) vs. 80.2% (65/81), allP < 0.05]. The TCM syndrome cure and obvious effect rate and effective rate in high and low dose observation groups were higher than those in the control group [respectively 87.80% (72/82), 79.75% (63/79) vs. 74.07% (60/81) and 98.78% (81/82), 96.20% (76/79) vs. 96.30% (78/81)]; the cure and marked effective rate and effective rate of controlling symptoms of upper respiratory tract infection in high and low dose observation groups were higher than those in the control group [respectively 78.05% (64/82), 74.68% (59/79) vs. 65.43% (78/81) and 98.78% (81/82), 96.20% (76/79) vs. 96.30% (78/81)], comparisons of efficacy among the three groups possessed clinical practical significance, but the differences were not statistically significant (allP > 0.05). The percentages of neutrophils in high and low dose observation groups and control group were significantly lower than those before treatment (respectively 0.61±0.08 vs. 0.63±0.08, 0.62±0.08 vs. 0.64±0.08, 0.61±0.09 vs. 0.64±0.09, allP < 0.05). Yinhua Pinggan granule was safe in the prescribed course of treatment and range of therapeutic dose.Conclusions Yinhua Pinggan granule is a safe and effective drug in the treatment of patients with upper respiratory tract infection accompanied by syndrome of pathogen stagnated in lung-defense phase.

Epigenetic modifications of triterpenoid ursolic acid in activating Nrf2 and blocking cellular transformation of mouse epidermal cells.

Ursolic acid (UA), a well-known natural triterpenoid found in abundance in blueberries, cranberries and apple peels, has been reported to possess many beneficial health effects. These effects include anticancer activity in various cancers, such as skin cancer. Skin cancer is the most common cancer in the world. Nuclear factor E2-related factor 2 (Nrf2) is a master regulator of antioxidative stress response with anticarcinogenic activity against UV- and chemical-induced tumor formation in the skin. Recent studies show that epigenetic modifications of Nrf2 play an important role in cancer prevention. However, the epigenetic impact of UA on Nrf2 signaling remains poorly understood in skin cancer. In this study, we investigated the epigenetic effects of UA on mouse epidermal JB6 P+ cells. UA inhibited cellular transformation by 12-O-tetradecanoylphorbol-13-acetate at a concentration at which the cytotoxicity was no more than 25%. Under this condition, UA induced the expression of the Nrf2-mediated detoxifying/antioxidant enzymes heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1 and UDP-glucuronosyltransferase 1A1. DNA methylation analysis revealed that UA demethylated the first 15 CpG sites of the Nrf2 promoter region, which correlated with the reexpression of Nrf2. Furthermore, UA reduced the expression of epigenetic modifying enzymes, including the DNA methyltransferases DNMT1 and DNMT3a and the histone deacetylases (HDACs) HDAC1, HDAC2, HDAC3 and HDAC8 (Class I) and HDAC6 and HDAC7 (Class II), and HDAC activity. Taken together, these results suggest that the epigenetic effects of the triterpenoid UA could potentially contribute to its beneficial effects, including the prevention of skin cancer.

Effect and mechanism of application in canicular days plus enteral nutrition for cough variant asthma in kids / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of application in canicular days plus enteral nutrition in treating cough variant asthma (CVA) in kids, and to explore its action mechanism. Methods:Following a randomized controlled single-blind parallel-group design, 138 eligible kids with CVA were randomized into an observation group, a canicular-day application group, and an enteral nutrition group, 46 kids in each group. The canicular-day application group was intervened by application in canicular days, the enteral nutrition group was by enteral feeding, and the observation group was by both canicular-day application and enteral feeding. The therapeutic efficacies were evaluated after a treatment course. Results: The recovery rate and total effective rate were respectively 50.0% and 98.0% in the observation group, versus 23.9% and 91.3% in the canicular-day application group, and 13.0% and 78.6% in the enteral nutrition group. The observation group was significantly superior to the other two groups (bothP<0.05). In comparing the global symptom score, peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), CD3+, CD4+, CD4+/CD8+, CD8+, hemoglobin (Hb), total protein (TP), albumin (ALB), eosinophil cationic protein (ECP), lipid peroxide (LPO), leukotriene (LT), body weight (BW), triceps skin-fold (TSF), and arm muscle circumference (AMC), the observation group was significantly better than the other two groups (bothP<0.05). Conclusion:Application in canicular days plus enteral nutrition can significantly improve the pulmonary function and symptoms in children’s CVA, and the effect is possibly produced by regulating cellular immune system, enhancing Hb, TP, ALB, BW, TSF, AMC, and inhibiting the production of ECP, LPO, and LT.

Current Perspectives on Epigenetic Modifications by Dietary Chemopreventive and Herbal Phytochemicals.

Studies during the last two decades have revealed the involvement of epigenetic modifications in the development of human cancer. It is now recognized that the interplay of DNA methylation, post-translational histone modification, and non-coding RNAs can interact with genetic defects to drive tumorigenesis. The early onset, reversibility, and dynamic nature of such epigenetic modifications enable them to be developed as promising cancer biomarkers and preventive/therapeutic targets. In addition to the recent approval of several epigenetic therapies in the treatment of human cancer, emerging studies have indicated that dietary phytochemicals might exert cancer chemopreventive effects by targeting epigenetic mechanisms. In this review, we will present the current understanding of the epigenetic alterations in carcinogenesis and highlight the potential of targeting these mechanisms to treat/prevent cancer. The latest findings, published in the past three years regarding the effects of dietary phytochemicals in modulating epigenetic mechanisms will also be discussed.

Induction of NRF2-mediated gene expression by dietary phytochemical flavones apigenin and luteolin.

Apigenin (API) and luteolin (LUT) have been used as therapeutic agents in folk medicine for thousands of years. These compounds exert a variety of biological activities, including anticancer, antioxidant and antiinflammatory activities. This study investigated whether API and LUT could activate Nrf2-antioxidant response element (ARE)-mediated gene expression and induce antiinflammatory activities in human hepatoma HepG2 cells. The compounds did not exhibit any substantial toxicity at low doses (1.56-6.25 µm). The induction of ARE activity was assessed in HepG2-C8 cells after treatment with low doses of API and LUT for 6 and 12 h. It was found that the induction of ARE activity by these compounds at the higher doses was comparable to the effects of the positive control, SFN at a dose of 6.25 µm. Exposure to the PI3K inhibitor LY294002 abolished ARE activation by both API and LUT, whereas the ERK-1/2 inhibitor PD98059 only decreased ARE activity induced by API. Both compounds significantly increased the endogenous mRNA and protein levels of Nrf2 and Nrf2 target genes with important effects on heme oxygenase-1 (HO-1) expression. API and LUT significantly and dose-dependently decreased the production of nitric oxide (NO), nitric oxide synthase (iNOS) and cytosolic phospholipase A2 (cPLA2), which were induced by the treatment of HepG2 cells with 1 µg/ml of lipopolysaccharide (LPS) for 24 h. The results indicate that API and LUT significantly activate the PI3K/Nrf2/ARE system, and this activation may be responsible for their antiinflammatory effects, as demonstrated by the suppression of LPS-induced NO, iNOS and cPLA2.

Blocking of JB6 cell transformation by tanshinone IIA: epigenetic reactivation of Nrf2 antioxidative stress pathway.

Increasing numbers of natural products have been found to possess anticancer effects. Nuclear factor erythroid-2-related factor-2 (Nrf2) is a master regulator of the antioxidative stress response, and our previous studies found that epigenetic modification of the Nrf2 gene appears to be a critical mechanism. Salvia miltiorrhiza, a Chinese herbal medicine widely used in Asian countries, has been shown to possess anticancer and antioxidant effects. Tanshinone IIA (TIIA), an active component in S. miltiorrhiza, has been reported to activate Nrf2 pathway. The objective of this study was to investigate the epigenetic regulation of Nrf2 by TIIA in mouse skin epidermal JB6 cells and the functional consequences for cell transformation. TIIA was found to induce antioxidant response element-luciferase and upregulate the mRNA and protein levels of Nrf2 and Nrf2 downstream target genes HO-1 and NQO-1. TIIA decreased the colony formation of JB6 cells by approximately 80%. TIIA decreased the protein levels of DNMT1, DNMT3a, DNMT3b, and HDAC3 and inhibited the enzymatic activity of HDACs. Bisulfite genomic sequencing indicated that TIIA demethylated the first five CpGs in the promoter region of the Nrf2 gene. Chromatin immunoprecipitation assays showed that TIIA treatment increased the recruitment of RNA polymerase II at Nrf2 transcription start site but had limited effects on enrichment of Ac-H3 in Nrf2 promoter. Taken together, our results show that TIIA activates the Nrf2 signaling pathway and induces epigenetic demethylation of the CpGs of Nrf2. The epigenetic reactivation of the Nrf2 signaling pathway by TIIA could potentially contribute to the attenuation of JB6 cellular transformation and anticancer effects.

Effect of Electroacupuncture Combined with Stretta Radiofrequency Treatment on MTL and GAS in Patients with Gastroesophageal Reflux Disease / 针灸推拿医学（英文版）

Objective: To observe the effect of electroacupuncture (EA) combined with Stretta radiofrequency treatment on contents of motilin (MTL) and gastrin (GAS) in gastroesophageal reflux disease (GERD) patients. Methods: A total of 90 eligible GERD cases were randomly allocated into three groups, 30 in each group. Patients in the EA group were treated with EA, patients in the radiofrequency group were treated with Stretta radiofrequency, and patients in the observation group were treated with EA combined with Stretta radiofrequency. Assessment was made after a course of treatment. Results: The recovery, improvement and failure cases and total effective rate in the EAgroup were 2, 18, 10 and 67.7% respectively, versus 13, 13, 4 and 86.7% in the radiofrequency group and 20, 9, 1 and 96.7% in the observation group. The therapeutic efficacy in the observation group was significantly better than that in the other two groups (P Conclusion: EA combined with Stretta radiofrequency treatment can significantly improve the clinical effect of GERD patients, improve regurgitation, heartburn and substernal burning pain and increase the contents of MTL and GAS.

Observation on Therapeutic Effects of Acupuncture plus Psychological Intervention for Postpartum Depression / 针灸推拿医学（英文版）

Objective: To observe the therapeutic effect of acupuncture plus psychological intervention for postpartum depression. Methods: By random number table, 85 patients with postpartum depression were divided into a treatment group and a control group. Forty-three cases in the treatment group were treated by acupuncture plus psychological intervention, once every day, five sessions per week, and rest at weekend. Forty-two cases in the control group were treated by oral administration of Fluoxetine Hydrochloride, 20 mg, once per day. The two groups were treated continuously for six weeks. The change of the score in Hamilton depression scale (HAMD) was observed and the therapeutic effect was summarized. Results:The total effective rate was 90.7%in the treatment group and 90.5% in the control group. The difference in the total effective rate between two groups was not statistically significant (P>0.05). In the intra-group comparisons of HAMD scores two, four and six weeks after treatment in both groups with those before treatment, the differences were statistically significant (all P0.05). Regarding the adverse events, 5 cases had nausea, 3 cases had dizziness, and 6 cases had poor appetite in the control group; no obvious adverse events happened in the treatment group. Conclusion:Acupuncture plus psychological intervention for postpartum depression is as same as oral administration of Fluoxetine Hydrochloride in therapeutic effects, but it does not have adverse reaction.

Targeting epigenetics for cancer prevention by dietary cancer preventive compounds--the case of miRNA.

In cancer, genetic mutations have long been considered to be the only driver of neoplasia. However, there is increasing evidence that epigenetic alterations could also play a major role in carcinogenesis and cancer. A number of experimental and epidemiologic studies have shown that many classes of dietary phytochemicals possess cancer-preventive and epigenetic-modifying properties. The report by Derry and colleagues in this issue of the journal shows that grape seed extract (GSE) prevents azoxymethane (AOM)-induced colon colitis via epigenetic microRNA (miRNA) regulation. Although the precise mechanism underlying the control of miRNA expression is not well understood currently, epigenetic changes could play a major role. This report, along with increasing evidence showing the impact of dietary phytochemicals on epigenetic activities, offers new perspectives on miRNA and epigenetic regulation in cancer prevention.