Could nutrition status predict fatigue one week before in patients with nasopharynx cancer undergoing radiotherapy?

BACKGROUND: Patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy experience significant fatigue, which is frequently underestimated due to the lack of objective indicators for its evaluation. This study aimed to explore the longitudinal association between fatigue and nutrition status 1 week in advance. METHODS: From January 2021 to June 2022, a total of 105 NPC patients who received intensity-modulated radiation therapy were enrolled in the observational longitudinal study. The significant outcomes, including the Piper Fatigue Scale-12 (PFS-12), the Scored Patient-Generated Subjective Global Assessment (PG-SGA), four body composition indices, and the Hospital Anxiety and Depression Scale (HADS), were assessed weekly from pre-treatment until the completion of radiotherapy (T0-T7) to explore their relationship. RESULTS: The trajectories of PFS-12 and all dimensions for 105 participants reached a peak during the fifth week. Sensory fatigue consistently received the highest scores (T0 = 1.60 ± 2.20, T5 = 6.15 ± 1.57), whereas behavior fatigue exhibited the fastest increase over time (T0 = 1.11 ± 1.86, T5 = 5.47 ± 1.70). Higher PG-SGA scores were found to be weakly explainable for aggravating fatigue (ß = 0.02 ~ 0.04). Unlike generalized additive mixed models, marginal structural models (MSM) produced larger effect values (ß = 0.12 ~ 0.21). Additionally, body composition indices showed weakly negative relationships with fatigue in MSMs one week in advance. CONCLUSIONS: The PG-SGA may be a more accurate predictor of future-week fatigue than individual body composition indicators, particularly when HADS is controlled for as a time-dependent confounder.

Elucidation the mechanism of the active ingredient imperatorin promoting drug absorption in cell model.

Imperatorin (IMP) is the main bioactive furanocoumarin of Angelicae dahuricae radix, which is a well-known traditional Chinese medicine. The purpose of this study was to elucidate the role of IMP in promoting absorption and the possible mechanism on the compatible drugs of Angelicae dahuricae radix. The influence of IMP on drugs' intestinal absorption was conducted by the Caco-2 cell model. The mechanism was studied by investigating the transcellular transport mode of IMP and its influence on P-glycoprotein (P-gp)-mediated efflux, protein expression of P-gp and tight junction, and cell membrane potential. The result showed IMP promoted the uptake of osthole, daidzein, ferulic acid, and puerarin and improved the transport of ferulic acid and puerarin in Caco-2 cells. The absorption-promoting mechanism of IMP might involve the reduction of the cell membrane potential, decrease of P-gp-mediated drug efflux and inhibition of the P-gp expression level in the cellular pathway, and the loosening of the tight junction protein by the downregulation of the expression levels of occludin and claudin-1 in the paracellular pathway. This study provides new insights into the understanding of the improved bioavailability of Angelicae dahuricae radix with its compatible drugs.

LY6D is crucial for lipid accumulation and inflammation in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is a serious metabolic disorder characterized by excess fat accumulation in the liver. Over the past decade, NAFLD prevalence and incidence have risen globally. There are currently no effective licensed drugs for its treatment. Thus, further study is required to identify new targets for NAFLD prevention and treatment. In this study, we fed C57BL6/J mice one of three diets, a standard chow diet, high-sucrose diet, or high-fat diet, and then characterized them. The mice fed a high-sucrose diet had more severely compacted macrovesicular and microvesicular lipid droplets than those in the other groups. Mouse liver transcriptome analysis identified lymphocyte antigen 6 family member D (Ly6d) as a key regulator of hepatic steatosis and the inflammatory response. Data from the Genotype-Tissue Expression project database showed that individuals with high liver Ly6d expression had more severe NAFLD histology than those with low liver Ly6d expression. In AML12 mouse hepatocytes, Ly6d overexpression increased lipid accumulation, while Ly6d knockdown decreased lipid accumulation. Inhibition of Ly6d ameliorated hepatic steatosis in a diet-induced NAFLD mouse model. Western blot analysis showed that Ly6d phosphorylated and activated ATP citrate lyase, which is a key enzyme in de novo lipogenesis. In addition, RNA- and ATAC-sequencing analyses revealed that Ly6d drives NAFLD progression by causing genetic and epigenetic changes. In conclusion, Ly6d is responsible for the regulation of lipid metabolism, and inhibiting Ly6d can prevent diet-induced steatosis in the liver. These findings highlight Ly6d as a novel therapeutic target for NAFLD.

Effects of Multimodal Exercise on Health-related Physical Fitness and Quality of Life in Patients with Nasopharyngeal Carcinoma during Radiotherapy.

BACKGROUND: The health-related physical fitness of patients with nasopharyngeal carcinoma can decrease significantly during radiotherapy, which can adversely affect their quality of life. AIM: This study was designed to evaluate the potential influence of a multimodal exercise program on the health-related physical fitness and quality of life of patients with nasopharyngeal carcinoma during radiotherapy. METHODS: Forty patients with nasopharyngeal carcinoma undergoing radiotherapy in the First Affiliated Hospital of Fujian Medical University from May to November 2019 were included. The participants in the control group (N=20) received routine nursing, while those in the intervention group (N=20) were also subjected to the multimodal exercise program during radiotherapy. RESULTS: The multimodal exercise program had a positive effect on participants. The step test index in the intervention group was significantly higher as compared to the control group (p < .05). The participants were subjected to 5 times slow speed (60°/s) and 10 times fast (180°/s) speed, and function of some extensor and flexor muscles of the elbow, shoulder, and knee joints in the intervention group was markedly improved (p < .05). In the intervention group, the grip strength of the right hand was observed to be significantly improved (p < .01). Furthermore, the upper limb scratch dorsal test of intervention group was significantly better than that of the control group (p < .05). The scores of physical, emotional, and social functions in the intervention group were found to be significantly higher as compared to the control group (p < .05). CONCLUSIONS: The multimodal exercise program significantly improved the health-related physical fitness and life quality of the patients with nasopharyngeal carcinoma during radiotherapy, though its long-term effects remain to be further analyzed.

Customizable Dual-Fluorescent Nanoparticles for Tracing and Quantifying of Cell Transport.

Purpose: Nanotechnology-based drug delivery systems (nano-DDS) have been developed to be a promising strategy to improve the efficacy, safety, physicochemical and pharmacokinetic/pharmacodynamics properties of drugs. It is very necessary to elucidate the delivery process in vivo or in cells for the rational design and accurate preparation of nano-DDS. The aim of this study was to construct a nano-DDS to visualize and quantify the intracellular behavior of the loaded cargo and carrier in such a system. Methods: A carboxyl-terminal end of poly(lactic-co-glycolic acid) polymer was fluorescently labeled with rhodamine B by conjugation of ethylenediamine. Dual-fluorescent nanoparticles (DFPs) were prepared from this fluorescently labeled polymer to encapsulate a fluorescent cargo, coumarin 6. The carrier and cargo of DFPs were monitored by confocal fluorescence microscopy during cellular uptake. Furthermore, the transcellular transportation of DFPs was evaluated quantitatively by measuring the fluorescence intensity. Results: The obtained fluorescent polymer showed stable and quantifiable characteristics. DFPs could be customized in terms of coumarin 6 content (97.7±1.0%), size (367.3±1.7 nm) and dual-emission fluorescence (green cargo and red carrier). DFPs did not significantly affect cell viability, the integrity of cell monolayers and the microscopic morphology at concentrations below 0.7 mg/mL within 3 h of co-incubation with Caco-2 cells. Multichannel fluorescence monitoring revealed that the fluorescence intensity of the carrier and cargo increased with time, but not synchronously. By calculating the residual, intracellular, and transport amounts of DFPs, the material balance between the total amount of cellular transport and the dose administered was obtained. Conclusion: Based on the advantages of dual fluorescent labeling, the differential behavior of cell trafficking can be visualized and quantitatively analyzed for the cargo and carrier of DFPs. These results provide insights into the cellular transport process of holistic nanoparticles and complement our understanding of the biological behaviors of nano-DDS.

Preparation, Characterization and Molecular Dynamics Simulation of Rutin-Cyclodextrin Inclusion Complexes.

Rutin is a natural flavonoid that carries out a variety of biological activities, but its application in medicine and food is limited by its water solubility. One of the classical methods used to enhance drug solubility is encapsulation with cyclodextrins. In this paper, the encapsulation of different cyclodextrins with rutin was investigated using a combination of experimental and simulation methods. Three inclusions of rutin/beta-cyclodextrin (ß-CD), rutin/2-hydroxypropyl beta-cyclodextrin (HP-ß-CD) and rutin/2,6-dimethyl beta-cyclodextrin (DM-ß-CD) were prepared by the freeze-drying method, and the inclusions were analyzed using Fourier infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), differential scanning calorimetry (DSC) and ultraviolet-visible spectroscopy (UV) to characterize and demonstrate the formation of the inclusion complexes. Phase solubility studies showed that rutin formed a 1:1 stoichiometric inclusion complex and significantly increased its solubility. ß-CD, HP-ß-CD, DM-ß-CD, rutin and the three inclusion complexes were modeled by using MS2018 and AutoDock 4.0, and molecular dynamics simulations were performed to calculate the solubility parameters, binding energies, mean square displacement (MSD), hydrogen bonding and radial distribution functions (RDF) after the equilibration of the systems. The results of simulation and experiment showed that rutin/DM-ß-CD had the best encapsulation effect among the three cyclodextrin inclusion complexes.

A Longitudinal Study of Stress in New Nurses in their First Year of Employment.

Objective: This study aimed to analyze changes in occupational stress in new nurses during the first year of employment. Methods: A prospective longitudinal study was conducted from 2020 to 2021 using one questionnaire four times on 127 newly employed nurses in a tertiary general teaching hospital in the province of Fujian. Results: The results showed that new nurses had moderate to high levels of stress in all four stages, with the highest stress level at 4 and 8 months of employment and the lowest stress level at 12 months; the differences in stress scores at different time points were statistically significant (p < 0.05). The trends in each stressor dimension varied across different periods. The highest scores were for pressure caused by "time allocation and workload," which peaked in month 8. The same trend was observed for stress from "patient care" and "work environment and equipment." "Management and interpersonal relationships" scored the highest overall stress score at the start of employment before declining. The lowest stress score was from "work environment and equipment" at the start of employment, and the lowest was from "management and interpersonal relationships" from month 4 onward. Conclusion: New nurses had higher overall occupational stress during their first year of employment under different stressors. Therefore, nursing managers should actively focus on stress factors of new nurses and provide targeted interventions to help them during their training period.

A Review on Increasing the Targeting of PAMAM as Carriers in Glioma Therapy.

Glioma is an invasive brain cancer, and it is difficult to achieve desired therapeutic effects due to the high postoperative recurrence rate and limited efficacy of drug therapy hindered by the biological barrier of brain tissue. Nanodrug delivery systems are of great interest, and many efforts have been made to utilize them for glioma treatment. Polyamidoamine (PAMAM), a starburst dendrimer, provides malleable molecular size, functionalized molecular structure and penetrable brain barrier characteristics. Therefore, PAMAM-based nanodrug delivery systems (PAMAM DDS) are preferred for glioma treatment research. In this review, experimental studies on PAMAM DDS for glioma therapy were focused on and summarized. Emphasis was given to three major topics: methods of drug loading, linkers between drug/ligand and PAMAM and ligands of modified PAMAM. A strategy for well-designed PAMAM DDS for glioma treatment was proposed. Purposefully understanding the physicochemical and structural characteristics of drugs is necessary for selecting drug loading methods and achieving high drug loading capacity. Additionally, functional ligands contribute to achieving the brain targeting, brain penetration and low toxicity of PAMAM DDS. Furthermore, a brilliant linker facilitates multidrug combination and multifunctional PAMAM DDS. PAMAM DDS show excellent promise as drug vehicles and will be further studied for product development and safety evaluation.

Pulmonary fibrosis model using micro-CT analyzable human PSC-derived alveolar organoids containing alveolar macrophage-like cells.

Human lung organoids (hLOs) are useful for disease modelling and drug screening. However, a lack of immune cells in hLOs limits the recapitulation of in vivo cellular physiology. Here, we generated hLOs containing alveolar macrophage (AMφ)-like cells derived from pluripotent stem cells (PSC). To bridge hLOs with advanced human lung high-resolution X-ray computed tomography (CT), we acquired quantitative micro-CT images. Three hLO types were observed during differentiation. Among them, alveolar hLOs highly expressed not only lung epithelial cell markers but also AMφ-specific markers. Furthermore, CD68+ AMφ-like cells were spatially organized on the luminal epithelial surface of alveolar hLOs. Bleomycin-treated alveolar hLOs showed upregulated expression of fibrosis-related markers and extracellular matrix deposits in the alveolar sacs. Alveolar hLOs also showed structural alterations such as excessive tissue fraction under bleomycin treatment. Therefore, we suggest that micro-CT analyzable PSC-derived alveolar hLOs are a promising in vitro model to predict lung toxicity manifestations, including fibrosis.

An assessment of the reliability and validity of the Chinese version of the Reporting of Clinical Adverse Events Scale for nursing interns: A cross-cultural adaptation of scales and online investigation.

AIM: The Reporting of Clinical Adverse Events Scale is a tool for evaluating the attitudes of medical staff toward reporting adverse events in clinical practice. This study aimed to assess the reliability and validity of the Reporting of Clinical Adverse Events Scale translated into Chinese used with trainee nurses in mainland China. DESIGN: The Chinese version of the Reporting of Clinical Adverse Events Scale was developed following guidelines for the cross-cultural adaptation of self-reporting measures. METHODS: The reliability and validity of the Chinese version of the Reporting of Clinical Adverse Events Scale was tested on 773 nursing interns by online investigation. Confirmatory factor analysis was performed on 350 questionnaires completed by the participants while exploratory factor analysis was performed on 423 questionnaires to test the structural validity of the scale. RESULTS: There were 23 items included in the Chinese version of the Reporting of Clinical Adverse Events Scale. The Cronbach's α-coefficient for the internal consistency of the total score was found to be 0.84 with a test-retest reliability value of 0.82, indicating a high level of reliability. Five common factors were extracted. The structural validity on the Kaiser-Meyer-Olkin test was 0.87 and the contribution rate of cumulative variance was 58.51%. The content validity values ranged between 0.86 and 1.00. CONCLUSION: The Chinese version of the Reporting of Clinical Adverse Events Scale is a valid and reliable tool for evaluating nursing interns' attitudes toward reporting clinical adverse events in China. This validation of the Chinese version of the scale also extends the use of the scale to a different population. TWEETABLE ABSTRACT: Nursing interns are responsible for a relatively high incidence of adverse events and their attitude to reporting these is crucial to patient safety. The Chinese version of the Reporting of Clinical Adverse Events Scale will be helpful for evaluating the reporting attitude of nursing interns.

Anxiety and depression status prior to radiotherapy in patients with nasopharyngeal carcinoma and its effect on acute radiation toxicities.

OBJECTIVE: The objective of this work is to explore anxiety and depression status prior to radiotherapy in patients with nasopharyngeal carcinoma (NPC) and its effect on acute radiation toxicities. METHODS: A total of 267 NPC patients were enrolled between August 2013 and September 2016. The anxiety and depression status of the patients prior to radiotherapy was evaluated using the Hospital Anxiety and Depression Scale. Acute radiation toxicities were assessed weekly and recorded according to the Common Terminology Criteria for Adverse Events version 4.0. Logistic regression analysis was used to identify the predictive factors for acute radiation toxicities. RESULTS: The rates of anxiety and depression status prior to radiotherapy were 35.2% and 25.5%, respectively. Anxiety was a significant predictor of vomiting (P = 0.001, OR = 2.874) and dysphagia (P = 0.029, OR = 2.080). Depression was a significant predictor of dysgeusia (P = 0.030, OR = 2.957). In addition, age was a significant predictor of dysphagia (P = 0.001, OR = 1.131). CONCLUSIONS: Anxiety and depression status prior to radiotherapy aggravate acute radiation toxicities in patients with NPC. Assessment of the anxiety and depression status and appropriate interventions should be an integral part of treatment to relieve radiation injury during intensity-modulated radiotherapy.

Evaluation of evidence for exercise intervention in patients with cancer-related fatigue during chemoradiotherapy.

AIM AND OBJECTIVES: This systematic review evaluated evidence quality for exercise intervention in patients with cancer-related fatigue (CRF) during chemoradiotherapy to provide evidence-based clinical guidance. BACKGROUND: Cancer-related fatigue is one of the most common symptoms in patients undergoing chemoradiotherapy. There is mounting evidence suggests exercise can relieve CRF and clinical practice guidelines for its management have been published in several countries. However, more specific exercise programmes need to be extracted to guide the clinical practice. DESIGN: The review was presented by PRISMA guidelines. Research questions and strategies were established using evidence-based nursing criteria. Eleven websites and databases were searched. Appraisal of Guidelines for Research and Evaluation II, the JBI literature quality assessment tool, and the JBI evidence pre-classification and evidence recommendation level system were used. RESULTS: Thirteen systematic reviews, four guidelines and one evidence summary were included. The overall guideline quality score was 5.71, indicating high quality, with the following average scores on the six dimensions: scope and purpose, 86.81%; stakeholder group, 71.53%; rigour of the writing, 76.56%; clarity of presentation, 88.19%; applicability, 68.23%; and independence, 72.92%. We summarised 18 pieces of evidence including screening and assessment of CRF and exercise risk, health education, sports programme, sports protection and termination index. There were 12, 1, 1 and 4 pieces of evidence in grades I, II, III and IV, respectively. The evidence recommendation was strong for 15 and weak for three articles. CONCLUSION: Although a normal adult exercise intensity level is considered safe for patients during chemoradiotherapy, our synthesis suggests that 18 pieces of evidence shall be followed. Future research should focus on more cancer types and more targeted exercise programme design. RELEVANCE TO CLINICAL PRACTICE: Cancer-related fatigue status and exercise risk should be screened and evaluated throughout exercise interventions. Interventions should be individualised, initiated at a low intensity and duration, and increased progressively.

The Effectiveness of Yoga on Cancer-Related Fatigue: A Systematic Review and Meta-Analysis.

PROBLEM IDENTIFICATION: The aim of this article is to evaluate the effectiveness of yoga on cancer-related fatigue (CRF) in patients undergoing chemotherapy and/or radiation therapy. LITERATURE SEARCH: Relevant English and Chinese articles were retrieved from medical databases and included in this analysis. Standardized critical appraisal instruments from the Joanna Briggs Institute were adopted for the quality assessment. DATA EVALUATION: 16 randomized controlled trials met the inclusion criteria. SYNTHESIS: Yoga interventions had a positive effect in reducing CRF among patients undergoing chemotherapy and/or radiation therapy, but the adherence to yoga was low. Mixed types of yoga, in addition to supervised and self-practicing strategies, were associated with increased patient adherence and improved CRF. IMPLICATIONS FOR PRACTICE: Yoga appears to be a safe and effective exercise for the management of CRF during chemotherapy and/or radiation therapy; however, additional high-quality studies are needed to define an optimal yoga intervention strategy.

Applicability of the Nutrition Risk Screening 2002 Combined with a Patient-Generated Subjective Global Assessment in Patients with Nasopharyngeal Carcinoma.

PURPOSE: This study aims to explore the applicability of the Nutrition Risk Screening 2002 (NRS2002) tool in screening nutritional risk and the Patient-Generated Subjective Global Assessment (PG-SGA) in determining nutrition status in nasopharyngeal carcinoma (NPC) patients. MATERIALS AND METHODS: NRS2002 and PG-SGA were simultaneously applied to evaluate the nutritional status of NPC patients before induction chemotherapy, as well as before and after radiotherapy. The PG-SGA results were considered golden standard in evaluating nutrition status, and the ROC curve value and Youden index were applied to analyze NRS2002 effectiveness in screening nutritional risk. RESULTS: A total of 102 NPC patients were included in this study. Patients with an NRS2002 score <3 and PG-SGA score ≥4 accounted for 5.3% (5/95), 19.6% (18/92) and 94.8% (36/38) at the time before induction chemotherapy, before radiotherapy and at the end of radiotherapy, respectively. The cut-off values of NRS2002 scores all <2 corresponded to the maximum Youden index at the three procedural times. And the area under curve (AUC) were 0.598 (P = 0.390), 0.665 (P = 0.015) and 0.940 (P = 0.034), respectively. At the end of radiotherapy, NRS2002 scores of <3 and <2 were used as cut-off values for nutritional risk screening, respectively. Additionally, the malnutrition-missed detection rates were 36.0% and 12.0% (χ 2 = 15.789; P <0.001). DISCUSSION: NRS2002 nutritional risk screening combined with the PG-SGA nutritional assessment has certain applicability in NPC. NRS2002 score ≥2 can be considered as a new cut-off point for nutritional assessment.

An Assessment of the Reliability and Factorial Validity of the Chinese Version of the Health Professional Education in Patient Safety Survey (H-PEPSS).

BACKGROUND: A nursing student's reflection on their knowledge and competence in patient safety (PS) may prepare them to provide safer care in certain circumstances. The Health Professional Education in PS Survey (H-PEPSS) is a validated tool for assessing the perceptions of nursing students with regards to competence in PS. The H-PEPSS is widely used internationally but is not available in Chinese. OBJECTIVES: This study aimed to translate the H-PEPSS into Chinese and test its psychometric properties among Chinese undergraduate nursing students. DESIGN: This was a cross-sectional online survey that was conducted in 2018. SETTINGS: Seven nursing schools in North, East, Northeast, Central, Southwest, South, and Northwest China. PARTICIPANTS: A total of 732 final-year undergraduate nursing students were recruited by convenience sampling. METHODS: Translation was conducted rigorously in accordance with an adapted version of Brislin's translation model. Psychometric evaluation was conducted by incorporating classical test theory and item response theory (IRT) analysis. RESULTS: The Chinese version of the H-PEPSS (both the classroom and clinical practice versions) achieved a Cronbach's α, marginal reliability and 2-week test-retest reliability of >0.85. A six-factor solution explaining 81.49% and 82.32% of the total variance was obtained for the classroom and clinical practice versions, respectively. This was further validated by confirmatory factor analysis. IRT analysis showed that the scale offers a broad range of information on PS competence and discriminates efficiently between patients with high and low levels of competence in PS. CONCLUSION: The Chinese version of the H-PEPSS is a reliable and valid instrument that is capable of evaluating competence in PS perceived by undergraduate nursing students. In addition, the survey may also be used to evaluate gaps in classroom knowledge and clinical competence, and to offer valid data for designing or tailoring new education strategies.

What influences nursing safety event reporting among nursing interns?: Focus group study.

BACKGROUND: Nursing safety events involving undergraduate nursing interns often occur but are under-reported. Only a few nursing schools have instituted formal reporting systems. The factors that affect reporting by undergraduate nursing interns are largely unknown. OBJECTIVE: The study aimed to explore the barriers and incentives to nursing safety event reporting by nursing interns. DESIGN: Focus groups were adopted to generate data for qualitative, thematic analyses. SETTINGS: Focus groups were held in intern dormitories during evenings or weekends. PARTICIPANTS: Purposive sampling strategies were employed. The participants were undergraduate nursing interns from one medical university in Fuzhou, China. METHODS: A total of six focus groups were conducted. Semi-structured questions guided the groups. RESULTS: Thirty-eight undergraduate nursing interns attended the groups. Barriers to nursing safety event reporting had five major themes: "Lack of knowledge," "Inconvenience of the reporting system," "Feeling of uncertainty and dishonor," "No benefit from reporting," and "Social influence." Incentives had three major themes: "Nursing safety event education," "Optimization of the reporting system," and "Anonymous reporting." Specific and targeted suggestions were considered, such as education by QQ or WeChat and the use of mobile devices. CONCLUSIONS: Nursing schools need to establish nursing safety event reporting systems for interns, and this needs to be accomplished in cooperation with teaching hospitals to clarify duties and management responsibilities. Practical and targeted management strategies need to be developed to foster reporting, improve nursing safety culture, and promote hospital quality.

Magnolin targeting of ERK1/2 inhibits cell proliferation and colony growth by induction of cellular senescence in ovarian cancer cells.

Ras/Raf/MEKs/ERKs and PI3 K/Akt/mTOR signaling pathways have key roles in cancer development and growth processes, as well as in cancer malignance and chemoresistance. In this study, we screened the therapeutic potential of magnolin using 15 human cancer cell lines and combined magnolin sensitivity with the CCLE mutaome analysis for relevant mutation information. The results showed that magnolin efficacy on cell proliferation inhibition were lower in TOV-112D ovarian cancer cells than that in SKOV3 cells by G1 and G2/M cell cycle phase accumulation. Notably, magnolin suppressed colony growth of TOV-112D cells in soft agar, whereas colony growth of SKOV3 cells in soft agar was not affected by magnolin treatment. Interestingly, phospho-protein profiles in the MAPK and PI3 K signaling pathways indicated that SKOV3 cells showed marked increase of Akt phosphorylation at Thr308 and Ser473 and very weak ERK1/2 phosphorylation levels by EGF stimulation. The phospho-protein profiles in TOV-112D cells were the opposite of those of SKOV3 cells. Importantly, magnolin treatment suppressed phosphorylation of RSKs in TOV-112D, but not in SKOV3 cells. Moreover, magnolin increased SA-ß-galactosidase-positive cells in a dose-dependent manner in TOV-112D cells, but not in SKOV3 cells. Notably, oral administration of Shin-Yi fraction 1, which contained magnolin approximately 53%, suppressed TOV-112D cell growth in athymic nude mice by induction of p16Ink4a and p27Kip1 . Taken together, targeting of ERK1 and ERK2 is suitable for the treatment of ovarian cancer cells that do not harbor the constitutive active P13 K mutation and the loss-of-function mutations of the p16 and/or p53 tumor suppressor proteins.

Influence of Lactobacillus plantarum on yogurt fermentation properties and subsequent changes during postfermentation storage.

This study aimed to evaluate the influence of 9 Lactobacillusplantarum with broad-spectrum antibacterial activity on fermented milk, including changes to the fermentation characteristics (pH, titration acidity, and viable counts), texture profile, relative content of volatile compounds, and sensory evaluation during 28-d storage at 4°C. First, L. plantarum IMAU80106, IMAU10216, and IMAU70095 were selected as candidates for further study because of their excellent coagulation and proteolytic activities. Subsequently, these L. plantarum strainswere supplemented to fermented milk produced by commercial yogurt starters (Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus) and a panel of parameters reflecting product quality was subsequently monitored during 28 d of postfermentation storage. The pH value and titration acidity of the fermented milk mildly fluctuated, whereas the L. plantarum viable counts remained stable along the storage period. Fourteen key volatile compounds were detected in the fermented milk by gas chromatography-mass spectrometry, and some flavor compounds were uniquely present in the L. plantarum-supplemented fermented milk (including 2,3-pentanedione, acetaldehyde, and acetate). No significant difference was shown in the sensory evaluation scores between samples with or without L. plantarum supplementation, but a gradual decrease was observed over storage in all samples. However, when L. plantarum was added, apparent shifts were observed in the overall quality of the fermented milk based on principal component analysis and multivariate ANOVA, particularly in the texture (adhesiveness) and volatile flavor compound profiles (acetaldehyde). Compared with L. plantarum IMAU80106 and IMAU10216, both the texture and volatile flavor profiles of IMAU70095 were closest to those of the control without adding the adjunct bacteria, suggesting that IMAU70095 might be the most suitable strain for further application in functional dairy product development. The current work has explored the potential of applying L. plantarum in fermented milk by performing thorough physical and chemical characterization. Our work is of intense interest to the dairy industry.

Effects of Probiotics on Intestinal Mucosa Barrier in Patients With Colorectal Cancer after Operation: Meta-Analysis of Randomized Controlled Trials.

Many studies have found that probiotics or synbiotics can be used in patients with diarrhea or inflammatory bowel disease for the prevention and treatment of some pathologies by improving gastrointestinal barrier function. However, there are few studies availing the use of probiotics in patients with colorectal cancer. To lay the foundation for the study of nutritional support in colorectal cancer patients, a meta-analysis has been carried out to assess the efficacy of probiotics on the intestinal mucosa barrier in patients with colorectal cancer after operation. To estimate the efficacy of probiotics on the intestinal mucosa barrier in patients with colorectal cancer after operation, a meta-analysis of randomized controlled trials has been conducted. Databases including PubMed, Ovid, Embase, the Cochrane Central Register of Controlled Trials, and the China National Knowledge Infrastructure have been searched to identify suitable studies. Stata 12.0 was used for statistical analysis, and sensitivity analysis was also conducted. Six indicators were chosen to evaluate probiotics in protecting the intestinal mucosa barrier in patients with colorectal cancer. Ratios of lactulose to mannitol (L/M) and Bifidobacterium to Escherichia (B/E), occludin, bacterial translocation, and levels of secretory immunoglobulin A (SIgA), interleukin-6 (IL-6), and C-reactive protein (CRP) were chosen to evaluate probiotics in protecting the intestinal mucosa barrier in patients with colorectal cancer. Seventeen studies including 1242 patients were selected for meta-analysis, including 5 English studies and 12 Chinese studies. Significant effects were found in ratios of L/M (standardized mean difference = 3.83, P = 0.001) and B/E (standardized mean difference = 3.91, P = 0.000), occludin (standardized mean difference = 4.74, P = 0.000), bacterial translocation (standardized mean difference = 3.12, P = 0.002), and levels of SIgA (standardized mean difference = 2.91, P = 0.004) and CRP (standardized mean difference = 4.21, P = 0.000), but no significant effects were found for levels of IL-6 (standardized mean difference = 1.33, P = 0.184). Probiotics can effectively protect the intestinal mucosa physical and biological barrier in patients with colorectal cancer after operation. However, to evaluate the protective effect on intestinal mucosal barrier, further studies on the type and concentration of the probiotics, duration of therapy, and the therapeutic route are required.

Magnolin inhibits cell migration and invasion by targeting the ERKs/RSK2 signaling pathway.

BACKGROUND: Magnolin is a natural compound abundantly found in Magnolia flos, which has been traditionally used in oriental medicine to treat headaches, nasal congestion and anti-inflammatory reactions. Our recent results have demonstrated that magnolin targets the active pockets of ERK1 and ERK2, which are important signaling molecules in cancer cell metastasis. The aim of this study is to evaluate the effects of magnolin on cell migration and to further explore the molecular mechanisms involved. METHODS: Magnolin-mediated signaling inhibition was confirmed by Western blotting using RSK2(+/+) and RSK2(-/-) MEFs, A549 and NCI-H1975 lung cancer cells, and by NF-κB and Cox-2 promoter luciferase reporter assays. Inhibition of cell migration by magnolin was examined by wound healing and/or Boyden Chamber assays using JB6 Cl41 and A549 human lung cancer cells. The molecular mechanisms involved in cell migration and epithelial-to-mesenchymal transition were determined by zymography, Western blotting, real-time PCR and immunocytofluorescence. RESULTS: Magnolin inhibited NF-κB transactivation activity by suppressing the ERKs/RSK2 signaling pathway. Moreover, magnolin abrogated the increase in EGF-induced COX-2 protein levels and wound healing. In human lung cancer cells such as A549 and NCI-H1975, which harbor constitutive active Ras and EGFR mutants, respectively, magnolin suppressed wound healing and cell invasion as seen by a Boyden chamber assay. In addition, it was observed that magnolin inhibited MMP-2 and -9 gene expression and activity. The knockdown or knockout of RSK2 in A549 lung cancer cells or MEFs revealed that magnolin targeting ERKs/RSK2 signaling suppressed epithelial-to-mesenchymal transition by modulating EMT marker proteins such as N-cadherin, E-cadherin, Snail, Vimentin and MMPs. CONCLUSIONS: These results demonstrate that magnolin inhibits cell migration and invasion by targeting the ERKs/RSK2 signaling pathway.