Proteomic analysis of ITPR2 as a new therapeutic target for curcumin protection against AFB1-induced pyroptosis.

Aflatoxin B1 (AFB1) is extremely carcinogenic and can cause liver cancer in humans and animals with continued ingestion. As a natural compound, curcumin (Cur) exhibits excellent anti-inflammatory, and anti-cancer properties with few side effects. In this study, a total of 60 male mice (6-week-olds, 15 per group). After one week of acclimatization feeding, the mice were divided into control group (Con), AFB1 group, curcumin group (Cur), and AF+Cur group. The mice were gavaged with curcumin (Cur, 100 mg/kg) and/or AFB1 (0.75 mg/kg). To identify a new therapeutic target for AFB1-induced pyroptosis, we performed proteomic profiling for curcumin alleviating liver injury caused by AFB1 to further validate the targets through volcano plot analysis, Venn analysis, heatmap analysis, correlation, cluster analysis, GO and KEGG enrichment. AFB1 exposure resulted in the loss of hepatocyte membrane, swelling of the endoplasmic reticulum, and a significant increase in transaminase (ALT and AST) contents, while curcumin greatly improved these changes. We found that differentially expressed proteins are enriched in the endoplasmic reticulum membrane and identified ITPR2 as a target of curcumin that alleviates AFB1-induced liver injury by proteomics. Furthermore, ITPR2 expression was detected by immunofluorescence, and qRT-PCR for mRNA expression of genes downstream of ITPR2 (calpain1, calpain2, caspase-12, caspase-3). ITPR2-activated endoplasmic reticulum stress-related proteins (calpain1, calpaini2, bcl-2, BAX, cl-caspase-12, cl-caspase-3), apoptosis (PARP) and pyroptosis (DFNA5) related proteins were examined by western blotting. The analysis showed that it effectively prevents AFB1-induced pyroptosis by lowering endoplasmic reticulum stress via interfering with ITPR2 and its downstream proteins (calpain1, calpain2, bcl-2, Bax) and inhibiting caspase-12/caspase-3 pathway. Conclusively, this study applied proteomic profiling to elucidate ITPR2 as a new target, which might give a new perspective on the mechanism of curcumin alleviating AFB1-induced pyroptosis.

The effectiveness of health education based on the 5Ts for teach-back on oral nutritional supplements compliance of post-discharge patients after surgery for gastric cancer: a randomized controlled trial.

OBJECTIVE: This study aims to explore the 5Ts teach-back(5Ts) to improve oral nutritional supplements (ONS) compliance of discharged patients after gastric cancer surgery. SETTING AND METHODS: Patients were recruited from the Bethune First Hospital of Jilin University. The patients were randomly assigned to 5Ts (n = 54) and routine health education (n = 54). Weekly ONS compliance was collected by "weekly ONS diary." ONS knowledge, health literacy, and health education satisfaction were collected at baseline and 5 weeks after discharge. Chi-square test, Mann-Whitney U test, and T test were used for data analysis. RESULTS: At the end of the intervention, there were 41 and 40 patients in intervention and control group. 5Ts significantly improve ONS compliance, ONS knowledge level (P = 0.000), health literacy level (P = 0.011), and health education satisfaction (P = 0.009) of patients. At the end of follow-up, there were 30 and 27 patients in two groups, and no significant difference in ONS compliance (P = 0.728). CONCLUSION: The 5Ts can significantly improve patients' ONS compliance and the effect of health education. TRIAL REGISTRATION NUMBER: This prospective trial was registered in the Chinese Clinical Trial Registry at ChiCTR2000040986 ( http://www.chictr.org.cn ). PATIENT OR PUBLIC CONTRIBUTION: Jia Wang and Haiyan Hu contributed to the performance of the study, analysis and interpretation the data, and drafted the manuscript; Jianan Sun and Qing Zhang contributed to the supervision of the study and interpreted the data; Zhiming Chen contributed to the analysis and interpretation the data; Qiuchen Wang contributed to the performance of the study and revised the manuscript; Mingyue Zhu contributed to interpretation the data; Jiannan Yao contributed to revise the manuscript; Hua Yuan and Xiuying Zhang contributed to the conception of the study, performed the study, interpreted the data, and significantly revised the manuscript. All authors screened the final version of the manuscript.

A four-compound remedy AGILe protected H9c2 cardiomyocytes against oxygen glucose deprivation via targeting the TNF-α/NF-κB pathway: Implications for the therapy of myocardial infarction.

Myocardial infarction (MI) is a highly prevalent and lethal disease worldwide. Prevention and timely recovery are critical for the control of the recurrence and heart failure in MI survivors. The present study was designed to investigate the cardioprotective activity of the herbal medicine formula Baoyuan Decoction (BYD) and identify the active compounds and molecular targets. The ethanolic BYD extract (BYDE) was prepared by water extraction and ethanol precipitation of four herbal medicines, Astragali Radix, Ginseng Radix et Rhizoma, Cinnamomi Cortex, and Glycyrrhizae Radix et Rhizoma. Initially, BYDE was validated for the cardioprotective effectiveness in a mouse model of ischemia injury and rat cardiomyocyte H9C2 cells. As results, BYDE effectively reduced infarct size from 56% to 37% and preserved cardiac functions in mouse MI model while protected H9C2 cells against oxygen glucose deprivation. Subsequent network pharmacology analysis revealed that 122 bioactive ingredients, including flavonoids and saponins from the UPLC-MS/MS profile of BYDE, might target 37 MI-related proteins, including inflammatory and apoptotic mediators (e.g., TNF, NFKB1, CASPs, TNFRSF1A, CXCL12, BCL2A1). Pathway enrichment analysis suggested that BYDE might control the cardiac inflammation via targeting the tumor necrosis factor-alpha (TNF-α)/nuclear factor-κB (NF-κB) pathway while the selected targets were also implicated in IL-17 signaling pathway, lipid and atherosclerosis. Consequently, adenosine, ginsenoside Rh2, isoliquiritigenin, and licochalcone A were selected to generate the four-compound mixture AGILe and validated for the inhibitory effects on the TNF-α/NF-κB pathway. The results of the present study suggested that the mixture AGILe might be a potential cardioprotective remedy against MI.

Effect of abdominal massage on feeding intolerance in patients receiving enteral nutrition: A systematic review and meta-analysis.

AIM: This study aimed to evaluate the effect of abdominal massage (AM) on feeding intolerance (FI) in patients receiving enteral nutrition (EN). DESIGN: A systematic review and meta-analysis. METHODS: We searched seven electronic databases to September 2021. STATA and RevMan were used to analyse the data. RESULTS: Eleven studies were included. The results revealed that AM could significantly reduce gastric residual volume and abdominal circumference difference, and reduce the incidence of gastric retention, vomiting, abdominal distention (all p < 0.001), diarrhoea (p = 0.02) and constipation (p = 0.002) in the experimental group. One study reported the incidence of aspiration in the control group was higher, but this was not statistically significant (p = 0.07). The meta-regression analysis showed there was a statistically significant correlation between intervention personnel and gastric residual volume (p = 0.035). CONCLUSION: AM could reduce the amount and incidence of gastric retention and the changes in abdominal circumference, and significantly reduce the incidence of gastrointestinal symptoms, without increasing the incidence of aspiration for EN patients. No Patient or Public Contribution.

The efficacy and mechanism of acupuncture in the treatment of male infertility: A literature review.

Fertility, a social, cultural, and medical issue, has aroused public attention because of its potential to predict future health. In recent years, the incidence of male infertility has increased significantly, and various risk factors, such as congenital factors, acquired factors, and idiopathic factors, have led to this situation. Male infertility causes substantial psychological and social distress in patients. With the implementation of the two-child policy, male infertility has brought enormous psychological and social pressure and huge economic burden to patients and the healthcare system. This has attracted the attention of not only men of childbearing age but also many male experts. The conventional therapeutic approaches for treating male infertility, including drugs, varicocele surgery, intrauterine insemination, in vitro fertilization, and intracytoplasmic sperm injection, can restore fertility to a certain extent, but their efficacy is far from satisfactory, not to mention some adverse events. Therefore, acupuncture has been chosen by many men to treat their infertility and produced significant effects. In the present paper, the efficacy and mechanism of acupuncture in the treatment of male infertility were analyzed from different perspectives such as regulating hormone secretion, reducing inflammation, and improving semen parameters. The existing literature shows that acupuncture can effectively treat male infertility.

Effect of Curcumin as Feed Supplement on Immune Response and Pathological Changes of Broilers Exposed to Aflatoxin B1.

In this study, we examined the protective effects of curcumin against the AFB1-induced immune response of and pathological changes in broilers. Histopathology examinations showed that at day 28, AFB1 (5 mg/kg) exposure leads to severe histological changes in the spleen, thymus and bursa of Fabricius with a decrease in the number and karyoplasmic area ratio of plasma cells. Curcumin alleviated the AFB1-induced immune organs' damage as well as the changes in plasma cells in a dose-dependent manner. RT-PCR data showed that AFB1 significantly downregulated the IL-2 and IFN-γ mRNA expression levels in the thymus, spleen and bursa of Fabricius. However, curcumin supplementation improved the AFB1-induced immune organs' damage via upregulated cytokines' expression. Intriguingly, similar trends were noticed in abnormal morphological changes and the immune response at day 35 after the withdrawal of AFB1 and curcumin from the diet, suggesting the protective effects and immunomodulatory function against AFB1 in broilers. The current study provides a scientific experimental basis for the application of curcumin as a therapeutic drug or additive in animal husbandry productive practice.

Preferences of oral nutritional supplement therapy among postoperative patients with gastric cancer: Attributes development for a discrete choice experiment.

BACKGROUND: Adherence to oral nutritional supplement therapy among postoperative patients with gastric cancer is low. There is little knowledge about patients' priorities and needs regarding oral nutritional supplement therapy. The discrete choice experiment is an innovative method used to elicit patients' preferences. Good practice guidelines emphasize that the development of attributes and levels is a fundamentally important process. OBJECTIVE: To comprehensively describe the identification, refinement, and selection of attributes and levels for a discrete choice experiment. METHODS: A mixed-methods approach, consisting of three consecutive steps: a literature review, in-depth interviews, and focus groups. First, the literature review allowed quick identification of attributes and levels. Then, 15 in-depth interviews were conducted to gather a rich description of the experience of patients taking oral nutritional supplements after gastrectomy and to verify and enrich the attributes and levels list. Finally, four focus group participants discussed the wording of the attributes and levels and reduced the number of attributes to manageable numbers through voting ranking methods. RESULTS: Following the literature review and qualitative data collection, eight attributes were finally generated, each with two to three levels. The following attributes were included: 1) information provider; 2) health guidance approach; 3) adverse reactions; 4) flavor; 5) follow-up method; 6) follow-up frequency; 7) psychological support; 8) cost. These attributes covered the important attributes of nutritional preparations and health guidance included in ONS therapy that were relevant to patients. CONCLUSIONS: This study's mixed-methods approach has been found highly suitable to identify, refine and select attributes and levels for a discrete choice experiment. The three methods have pros and cons, and they complement each other, especially the analysis of qualitative data led to a deeper and broader understanding of attributes and levels.

Mori fructus aqueous extracts attenuate carbon tetrachloride-induced renal injury via the Nrf2 pathway and intestinal flora.

Mori fructus aqueous extracts (MFAEs) have been used as a traditional Chinese medicine for thousands of years with the function of strengthening the liver and tonifying the kidney. However, its inner mechanism to alleviative renal injury is unclear. To investigate the attenuation of MFAEs on nephrotoxicity and uncover its potential molecular mechanism, we established a nephrotoxicity model induced by carbon tetrachloride (CCl4). The mice were randomly divided into control group, CCl4 model group (10% CCl4), CCl4 + low and high MFAEs groups (10% CCl4 + 100 mg/kg and 200 mg/kg MFAEs). We found that MFAEs decreased the kidney index of mice, restored the pathological changes of renal structure induced by CCl4, reduced cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (Kim-1) blood urea nitrogen and creatinine contents in serum, promoted the nuclear transportation of Nrf2 (nuclear factor erythroid derived 2 like 2), elevated the expression of HO-1 (heme oxygenase 1), GPX4 (glutathione peroxidase 4), SLC7A11 (solute carrier family 7 member 11), ZO-1 (zonula occludens-1) and Occludin, suppressed the expression of Keap1 (kelch-like ECH-associated protein 1), HMGB1 (High Mobility Group Protein 1), ACSL4 (acyl-CoA synthetase long chain family member 4) and TXNIP (thioredoxin interacting protein), upregulated the flora of Akkermansia, Anaerotruncus, Clostridium_sensu_stricto, Ihubacter, Alcaligenes, Dysosmobacter, and downregulated the flora of Clostridium_XlVa, Helicobacter, Paramuribaculum. Overlapped with Disbiome database, Clostridium_XlVa, Akkermansia and Anaerotruncus may be the potential genera treated with renal injury. It indicated that MFAEs could ameliorate kidney injury caused by CCl4 via Nrf2 signaling.

Preferences for oral nutritional supplement therapy among postoperative patients with gastric cancer: a discrete choice experiment.

PURPOSES: Patients after gastrectomy have poor compliance with oral nutritional supplement (ONS) therapy. Incorporating patient preferences into treatment decisions allows possible product improvements or treatment focus adjustments. The purpose of this research was to investigate the preferences for ONS therapy among postoperative patients with gastric cancer, and to provide person-centered oral nutrition management strategies. METHODS: A discrete choice experiment was designed and implemented within a Chinese cancer population. The survey was administered via paper-based questionnaires during face-to-face interviews with assistance from health professionals. A mixed logit model was used to estimate respondents' preferences for different levels of nutrition therapy attributes. RESULTS: One hundred ninety respondents valued "Adverse reactions-almost none" (ß 3.43 [SE, 0.28]) the most, followed by "Flavor-good taste" (ß 0.68 [SE, 0.13]) and "Follow-up frequency-once every 2 weeks" (ß 0.52 [SE, 0.13]), and were willing to pay more for these attribute levels. Respondents would be 93.73% more likely to accept a nutrition therapy program if there were almost no adverse reactions compared to the frequent adverse reactions. CONCLUSIONS: Health professionals should pay attention to the management and prevention of adverse reactions when prescribing nutritional products, and provide diversified ONS products when necessary to meet patient preferences. When formulating intervention strategies, health professionals should also consider the different characteristics of patients, acknowledge the importance of the role of nurse specialists in a novel model of multidisciplinary nutritional care, standardize ONS information, follow up regularly, and encourage patients' families to participate in daily nutrition care.

Giant Aggressive Extraocular Sebaceous Carcinoma: A Case Report.

Sebaceous carcinoma (SC) is a rare, aggressive malignancy. Most lesions occur in the periocular region, with few cases presenting with extraocular lesions. Here, we report a case of an 89-year-old woman with a 3-month history of a rapidly growing giant extraocular SC. The diagnosis was based on skin biopsy findings. We advised the patient to undergo surgical excision of the carcinoma. However, the patient and her family rejected our proposed surgical treatment, opting for topical traditional Chinese medicine as alternative treatment. The patient subsequently died of unknown causes at home, four months after the first visit. This case of treatment failure emphasizes the importance of early detection and treatment for these aggressive tumors.

Assessment of compliance with oral nutritional supplementation and exploration of barriers and facilitators for patients after gastrectomy: A mixed-methods study.

AIMS: To evaluate the compliance of patients after gastrectomy in taking oral nutritional supplementation and to explore the promoting and hindering factors. DESIGN: A mixed-methods design with an explanatory sequential approach was employed. METHODS: We conducted a 12-week longitudinal study to evaluate the oral nutritional supplementation compliance of 122 patients after gastric cancer surgery and the factors that affected their compliance. After the quantitative phase, we selected the interview subjects and developed the interview outline based on the analysis of the quantitative results. In-depth interviews (n = 15) were conducted to explain and supplement the quantitative phase results. Data were collected from October 2019 to May 2020. RESULTS: The average overall compliance rate of oral nutritional supplementation in patients with gastric cancer over 12 weeks was 30.59%. Adverse reactions to oral nutritional supplementation, the identity of the main caregivers and the patient's financial ability were independent factors that affected patient compliance. In subsequent interviews, we extracted four themes: social support plays an important role in patients taking oral nutritional supplementation, adverse reactions discourage patients from continuing to take oral nutritional supplementation, patients' attitudes affect their motivation to take oral nutritional supplementation, and the different needs of patients for oral nutritional supplementation affect patient compliance. CONCLUSION: Patients' compliance with oral nutritional supplementation after gastric cancer surgery is very low. Health education should pay more attention to the management of adverse reactions and the role of patients' peers and family members. Oral nutritional supplementation products should be diversified to provide patients with more choices. IMPACT: This study clarifies the factors that hinder and promote oral nutritional supplementation compliance and provides an important reference for the establishment and revision of health education strategies for patients after gastric cancer surgery.

Assessment of adherence to oral nutritional supplementation and exploration of barriers and facilitators in patients after gastric cancer surgery: a mixed methods study protocol.

INTRODUCTION: Postoperative malnutrition is a major issue in patients with gastric cancer. The European Society for Clinical Nutrition and Metabolism recommends oral nutritional supplements (ONS) as a first-line nutritional therapy to prevent malnutrition in patients with cancer. However, adherence to ONS is unsatisfactory. The overall aim of this study was to evaluate the adherence of patients with gastric cancer to ONS and to explore the promoting and hindering factors. METHODS AND ANALYSIS: In this study, we will use mixed methods with an explanatory sequential approach for data collection and analysis. In the first phase, a 12-week longitudinal study will be performed to identify changes in trends of oral nutritional supplementation adherence in 135 patients with gastric cancer, the impact of adherence on nutritional indicators and clinical outcomes and ONS adherence-related factors. The primary endpoints include patient adherence to ONS, weight, body mass index and grip strength followed by 30-day readmission rate, complications and adverse reactions. In the second stage, qualitative research will be implemented to provide in-depth insight into the quantitative results. Finally, quantitative and qualitative results will be combined for analysis and discussion to put forward suggestions for improving patients' ONS adherence. ETHICS AND DISSEMINATION: This research protocol has been approved by the Ethics Committee of the School of Nursing, Jilin University, China (No. 2019101601). Results will be disseminated in peer-reviewed journals and conferences, and sent to participating practices. TRIAL REGISTRATION NUMBER: ChiTR2000032425.

Curcumin ameliorates duodenal toxicity of AFB1 in chicken through inducing P-glycoprotein and downregulating cytochrome P450 enzymes.

It has been reported that oral intake of aflatoxin B1 (AFB1)-contaminated feed could cause acute, sub-chronic, or chronic toxicity in livestock and poultry. However, the harmful effect of AFB1 on the small intestine is still controversial. Therefore, blocking the entry of AFB1 into the body through the digestive tract is one of the important methods to prevent its toxicity. In the present study, 1-day-old Arbor Acres broilers were randomly divided into 6 groups including control group, curcumin control group (450 mg curcumin/kg feed), curcumin low-, medium-, and high-dose group (150, 300, and 450 mg curcumin/kg feed + 5 mg AFB1/kg feed), and AFB1 group (5 mg AFB1/kg feed). After 28 d, the samples of chickens' duodenums were collected for further analyses. AFB1 caused abnormal functional and morphological changes in the duodenum, including histological lesions, increased the length of the duodenum and depth of crypt, decreased the unit weight of the duodenum, height of villus, and the value of villus height/crypt depth. Meanwhile, AFB1 administration enhanced malonaldehyde activity, 8-HOdG level, and the mRNA expression of cytochrome P450 (CYP450) enzymes, and reduced superoxide dismutase, catalase, adenosine triphosphatase (ATPase) activity and the mRNA expression of Abcb1. Importantly, curcumin supplementation partially ameliorated AFB1-induced abnormal functional and morphological signs of the duodenum, alleviated AFB1-induced oxidative stress, and decreased the mRNA expression of CYP450 enzymes. Furthermore, curcumin ameliorated AFB1-induced decrease in the Abcb1 mRNA expression, P-glycoprotein (P-gp) level, and ATPase activities. It has been suggested from these results that curcumin supplementation in the feed could ameliorate AFB1-induced duodenal toxicity and damage through downregulating CYP450 enzymes, promoting ATPase activities, and inducing P-gp in chickens.

The Role of Spirituality in Patients Undergoing Hematopoietic Stem Cell Transplantation: a Systematic Mixed Studies Review.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) has become the standard treatment for many diseases, but it is an intense and distinctive experience for patients. HSCT-related mortality is present throughout the whole process of transplantation, from pretransplantation to recovery. Long-term rehabilitation and the uncertain risk of death evoke feelings of vulnerability, helplessness, and intense fear. Zimmermann et al. proposed that spiritual well-being is an important dimension of quality of life and that patients at the end stage of life require spiritual support in addition to physical care, psychological care, and social support. Therefore, the purpose of this review is to examine the role of spirituality in the process of HSCT. METHOD: A systematic mixed studies review (SMSR) was based on Pluye and Hong's framework to understand the role of spirituality in patients' experiences while undergoing HSCT. We use the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement to report the results of integration. RESULTS: Fifteen original qualitative studies, 19 quantitative studies, and one mixed method study were included in the systematic mixed studies review. The evidence from the review revealed the following three themes: the spiritual experiences of HSCT patients, the spiritual coping styles of HSCT patients, and the spiritual need changes brought about by HSCT. DISCUSSION: Few medical institutions currently offer spiritual healing, although HSCT patients with different cultural backgrounds may have different spiritual experiences and spiritual coping styles. Psychotherapists or nurses should be considered to provide spiritual care for patients undergoing HSCT, to help patients cope with disease pressures, promote HSCT patients' comfort, and improve their quality of life.

Effects of enteral nutritional rich in n-3 polyunsaturated fatty acids on the nutritional status of gastrointestinal cancer patients: a systematic review and meta-analysis.

Postoperative malnutrition is a major issue among gastrointestinal cancer patients. Because n-3 polyunsaturated fatty acids (n-3 PUFAs) have immunological benefits, n-3 PUFAs are widely used in oral nutritional supplements (ONS). However, n-3 PUFAs in ONS reduced patients' compliance with ONS and affected the role of ONS in maintaining the postoperative nutritional status of patients. The aim of this study was to systematically explore the benefits of enteral nutrition rich in n-3 PUFAs in maintaining the nutritional status of patients after gastrointestinal surgery. Databases including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and VIP databases were searched through March 16, 2019. The references of related reviews and studies were assessed up to March 16, 2019. The effect sizes from individual studies were calculated as the standardized mean difference (SMD), mean difference (MD), and risk ratio (RR) with 95% confidence intervals (95% CIs). A total of 11 studies (n = 977) were included. In this systematic review and meta-analysis, we observed that enteral supplementation of n-3 PUFAs had no significant effect on weight (MD, 1.09; 95% CI, -0.90, 3.08), body mass index (MD, 0.55; 95% CI, -1.45, 2.54), albumin (SMD, 0.39; 95% CI, -0.10, 0.87), wound infections (RR, 0.87, 95% CI, 0.57, 1.33), or pneumonia (RR, 0.98; 95% CI, 0.60, 1.59) in gastrointestinal cancer patients. Thus, compared with enteral nutritional without n-3 PUFAs, enteral nutritional rich in n-3 PUFAs has no significant effects on nutritional status, incidence of pneumonia, or wound infections among gastrointestinal cancer patients during postoperative convalescence.

Detection of Aflatoxin adducts as potential markers and the role of curcumin in alleviating AFB1-induced liver damage in chickens.

In this study, we identified AFB1 adducts as potential markers and investigated the role of curcumin in alleviating AFB1-induced liver damage by suppressing the production of AFB1 adducts and oxidative stress in AA broilers liver. A total of 64 one-day-old Arbor Acres (AA) broilers were randomly divided into four groups, including control group, AFB1 group (5 mg/kg AFB1), cur + AFB1 group (300 mg/kg curcumin+5 mg/kg AFB1) and curcumin group (300 mg/kg). Serum biochemical parameters, liver antioxidant abilities, AFB1 adducts and oxidative stress mechanism were studied in broilers. AFB1 administration accompany with signs of liver injury, including hepatic histological lesions, increased serum enzymes activities, decreased liver antioxidant enzymes activities and the suppression of ROS and 8-OHdG. Meanwhile, Nrf2/HO-1 pathway was depressed by AFB1 treatment. Immunohistochemistry and ELISA showed that AFB1 significantly increased AFB1-DNA adduct in liver (p < 0.05) and AFB1-lysine adduct in serum (p < 0.05). Importantly, supplementation of curcumin can ameliorate these alterations. Intriguingly, curcumin alleviated AFB1-induced toxicity and oxidative stress by inhibiting the generation of ROS, 8-OHdG and AFB1 adducts, and activated Nrf2 signaling pathway in broilers. Conclusively, our experiments suggest that curcumin could be considered as a potential agent for prevention of AFB1-induced toxicity and oxidative stress, and AFB1 adducts could be suitable therapeutic targets.

Susceptibility breakpoint for Danofloxacin against swine Escherichia coli.

BACKGROUND: Improper use of antimicrobials results in poor treatment and severe bacterial resistance. Breakpoints are routinely used in the clinical laboratory setting to guide clinical decision making. Therefore, the objective of this study was to establish antimicrobial susceptibility breakpoints for danofloxacin against Escherichia coli (E.coli), which is an important pathogen of digestive tract infections. RESULTS: The minimum inhibitory concentrations (MICs) of 1233 E. coli isolates were determined by the microdilution broth method in accordance with the guidelines in Clinical and Laboratory Standards Institute (CLSI) document M07-A9. The wild type (WT) distribution or epidemiologic cutoff value (ECV) was set at 8 µg/mL with statistical analysis. Plasma drug concentration data were used to establish pharmacokinetic (PK) model in swine. The in vitro time kill test in our study demonstrated that danofloxacin have concentration dependent activity against E.coli. The PK data indicated that danofloxacin concentration in plasma was rapidly increased to peak levels at 0.97 h and remained detectable until 48 h after drug administration. The pharmacodynamic cutoff (COPD) was determined as 0.03 µg/mL using Monte Carlo simulation. To the best of our knowledge, this is the first study to establish the ECV and COPD of danofloxacin against E.coli with statistical method. CONCLUSIONS: Compared to the COPD of danofloxacin against E.coli (0.03 µg/mL), the ECV for E.coli seemed reasonable to be used as the final breakpoint of danofloxacin against E.coli in pigs. Therefore, the ECV (MIC ≤8 µg/mL) was finally selected as the optimum danofloxacin susceptibility breakpoint for swine E.coli. In summary, this study provides a criterion for susceptibility testing and improves prudent use of danofloxacin for protecting public health.

Protective role of curcumin in ameliorating AFB1-induced apoptosis via mitochondrial pathway in liver cells.

It is well documented that liver is the primary target organ of aflatoxin B1 (AFB1) and curcumin proved to be effective against AFB1-induced liver injury. In the present study, we investigated the preventive effects of curcumin against AFB1-induced apoptosis through the molecular regulation of p53, caspase-3, Bax, caspase-9, Bcl-2 and cytochrome-C associated with mitochondrial pathway. Liver antioxidant levels were measured. The hallmarks of apoptosis were analysed by methyl green-pyronin-Y staining, transmission electron microscopy, RT-PCR and western blot. Results revealed that dietary curcumin ameliorated AFB1-induced oxidative stress in a dose-dependent manner. Methyl green-pyronin-Y staining and transmission electron microscopy showed that AFB1 induced apoptosis and caused abnormal changes in liver cells morphology such as condensation of chromatin material, reduces cell volume and damaged mitochondria. Moreover, mRNA and protein expression results manifested that apoptosis associated genes showed up-regulation in AFB1 fed group. However, the supplementation of dietary curcumin (dose-dependently) alleviated the increased expression of the apoptosis associated genes at mRNA and protein level, and restored the hepatocytes normal morphology. The study provides an insight and a better understanding of the preventive mechanism of curcumin against AFB1-induced apoptosis in hepatocytes and provide scientific basis for the therapeutic uses of curcumin.

Radix Astragali and Tanshinone Help Carboplatin Inhibit B16 Tumor Cell Growth.

BACKGROUND: Excessive UV radiation causes increased melanoma incidence. Postoperation chemotherapy will destroy lymphocytes and compromise immune response. Immunodepression is also detected in patients with cancers. Previous studies suggested that polysaccharide-protein complexes manifested immunomodulatory and antitumor activities. Radix Astragali (RA) extract is a product of polysaccharide-protein complexes, which has been used in the treatment of a variety of diseases because of its low toxicity to the host. Tanshinone (TA) is a derivative of phenanthrenequinone isolated from Danshen, which is suggested to inhibit tumor growth by inducing apoptosis in tumor cells. Carboplatin (CA) is a commonly used chemotherapeutic drug in melanoma treatment. Therefore, we hypothesized that the combination of RA and TA will help CA better inhibit the B16 cell growth. PURPOSE: The study will test that the efficacy of growth inhibition of tumor cell produced by CA + RA + TA is better than CA + RA or CA + TA. METHODS: The B16 tumor cells were injected to Swiss-Hauschka (ICR) mice subcutaneously. Twenty-four hours later, mice received CA intraperitoneally, CA + RA (RA were administered gastrically at the dosage of 10 g/kg body weight), CA + TA (TA were administered gastrically at the dosage of 0.5 g/kg body weight), or no treatment (model group). Tumor weight, volume, latency, incidence, the percentage of CD4(+) and CD8(+) in spleen, and natural killer (NK), and cytotoxic lymphocyte (CTL) activities were measured and compared among different groups. RESULTS: Compared with mice treated with CA + RA, CA + TA, or CA alone, the mice treated with CA + RA + TA showed (1) significantly smaller tumor weight and tumor volume; (2) significantly longer tumor latency; (3) significantly lower tumor incidence; and (4) significantly increased percentage of CD4(+) and CD8(+) in spleen and increased activities of NK and CTL. CONCLUSION: Combination of RA and TA can help CA produce more effective inhibition on B16 cell growth.