Sulforaphane-Enriched Extracts from Broccoli Exhibit Antimicrobial Activity against Plant Pathogens, Promising a Natural Antimicrobial Agent for Crop Protection.

Sulforaphane (SFN) is one of the hydrolysates of glucosinolates (GSLs), primarily derived from Brassica vegetables like broccoli. In clinical therapy, SFN has been proven to display antimicrobial, anticancer, antioxidant, and anti-inflammatory properties. However, the antimicrobial effects and mechanism of SFN against plant pathogens need to be further elucidated, which limits its application in agriculture. In this study, the genetic factors involved in SFN biosynthesis in 33 B. oleracea varieties were explored. The finding showed that besides the genetic background of different B. oleracea varieties, myrosinase and ESP genes play important roles in affecting SFN content. Subsequently, the molecular identification cards of these 33 B. oleracea varieties were constructed to rapidly assess their SFN biosynthetic ability. Furthermore, an optimized protocol for SFN extraction using low-cost broccoli curds was established, yielding SFN-enriched extracts (SFN-ee) containing up to 628.44 µg/g DW of SFN. The antimicrobial activity assay confirmed that SFN-ee obtained here remarkably inhibit the proliferation of nine tested microorganisms including four plant pathogens by destroying their membrane integrity. Additionally, the data demonstrated that exogenous application of SFN-ee could also induce ROS accumulation in broccoli leaves. These results indicated that SFN-ee should play a dual role in defense against plant pathogens by directly killing pathogenic cells and activating the ROS signaling pathway. These findings provide new evidence for the antimicrobial effect and mechanism of SFN against plant pathogens, and suggest that SFN-ee can be used as a natural plant antimicrobial agent for crop protection and food preservation.

Phenylalanine-Arginine-ß-Naphthylamide Enhances the Photobactericidal Effect of Methylene Blue on Pseudomonas aeruginosa.

Objective: To investigate the effectiveness, dosing sequence, concentration, and mechanism of antimicrobial photodynamic inactivation (aPDI) using methylene blue (MB) plus phenylalanine-arginine-ß-naphthylamide (PAßN) against Pseudomonas aeruginosa. Methods: P. aeruginosa bacterial suspension was incubated with MB for different times (5-240 min), and then, 10 J/cm2 red light was irradiated. The efflux pump inhibitor (EPI) PAßN (10-100 µg/mL) was combined with MB (1-20 µM) in different sequences (PAßN-first, PAßN+MB, PAßN-after). Colony-forming units were then determined by serial dilution. Results: Using MB 10 µM plus 10 J/cm2, the killing effect of MB-aPDI on P. aeruginosa increased first and then decreased with longer incubation time. The killing effect of MB+PAßN-aPDI on P. aeruginosa was better than that of MB-aPDI (p < 0.05) by up to 2 logs. PAßN-first had the best killing effect, whereas PAßN-after had the worst killing effect. The killing effect increased with PAßN concentration and at 100 µg/mL reached 5.1 logs. Conclusions: The EPI PAßN enhanced the bactericidal effect of MB-aPDI on P. aeruginosa, especially when added before MB. It is proposed that MB is a substrate of the resistance-nodulation-division family efflux pump.

LOXL2-dependent deacetylation of aldolase A induces metabolic reprogramming and tumor progression.

Lysyl-oxidase like-2 (LOXL2) regulates extracellular matrix remodeling and promotes tumor invasion and metastasis. Altered metabolism is a core hallmark of cancer, however, it remains unclear whether and how LOXL2 contributes to tumor metabolism. Here, we found that LOXL2 and its catalytically inactive L2Δ13 splice variant boost glucose metabolism of esophageal tumor cells, facilitate tumor cell proliferation and promote tumor development in vivo. Consistently, integrated transcriptomic and metabolomic analysis of a knock-in mouse model expressing L2Δ13 gene revealed that LOXL2/L2Δ13 overexpression perturbs glucose and lipid metabolism. Mechanistically, we identified aldolase A, glyceraldehyde-3-phosphate dehydrogenase and enolase as glycolytic proteins that interact physically with LOXL2 and L2Δ13. In the case of aldolase A, LOXL2/L2Δ13 stimulated its mobilization from the actin cytoskeleton to enhance aldolase activity during malignant transformation. Using stable isotope labeling of amino acids in cell culture (SILAC) followed by proteomic analysis, we identified LOXL2 and L2Δ13 as novel deacetylases that trigger metabolic reprogramming. Both LOXL2 and L2Δ13 directly catalyzed the deacetylation of aldolase A at K13, resulting in enhanced glycolysis which subsequently reprogramed tumor metabolism and promoted tumor progression. High level expression of LOXL2/L2Δ13 combined with decreased acetylation of aldolase-K13 predicted poor clinical outcome in patients with esophageal cancer. In summary, we have characterized a novel molecular mechanism that mediates the pro-tumorigenic activity of LOXL2 independently of its classical amine oxidase activity. These findings may enable the future development of therapeutic agents targeting the metabolic machinery via LOXL2 or L2Δ13. HIGHLIGHT OF THE STUDY: LOXL2 and its catalytically inactive isoform L2Δ13 function as new deacetylases to promote metabolic reprogramming and tumor progression in esophageal cancer by directly activating glycolytic enzymes such as aldolase A.

Association of handgrip strength with all-cause mortality: a nationally longitudinal cohort study in China.

OBJECTIVES: Handgrip strength is considered a vital and reliable measure of comprehensive physical assessments, whereas the association of handgrip strength with overall mortality risk among Chinese adults was less studied. We prospectively investigated the association between handgrip strength and all-cause mortality among Chinese middle-aged and older people based on data from the China Health and Retirement Longitudinal Study (CHARLS).3 DESIGN: Longitudinal cohort study. METHODS: Grip strength was assessed for both hands by a dynamometer. Odds ratios (ORs)4 and 95 % confidence intervals (CIs)5 were estimated applying logistic regression models with adjustments for age, body mass index, ethnicity, education level, annual household income, marital status, drinking, smoking, physical activity, and medical insurance among men and women. Deaths were ascertained by each follow-up survey in which the household member who lived with the participants were inquired. RESULTS: Over an average follow-up period of approximately 8 years among the screened 11,618 participants ≥45 years old, 1290 deaths were documented. The age range was 45-93 for men and 45-96 for women. Greater handgrip strength was associated with a lower overall mortality risk, with adjusted ORs (comparing with extreme tertiles) of 0.47 (95 % CI: 0.35-0.64; P-trend<0.001) in men and 0.51 (95 % CI: 0.24-1.08; P-trend = 0.059) in women. Such inverse association seemed stronger among younger men (OR = 0.29, 95 % CI: 0.18-0.45), compared with the older men (OR = 0.49, 95 % CI: 0.33-0.73; P-interaction = 0.023). CONCLUSIONS: Handgrip strength was inversely associated with all-cause mortality risk, especially among the younger men. Further investigations are warranted to elucidate the underlying mechanism.

Intermittent Fasting: Potential Bridge of Obesity and Diabetes to Health?

Obesity has been an escalating worldwide health problem for decades, and it is likely a risk factor of prediabetes and diabetes. Correlated with obesity, the number of diabetic patients is also remarkable. A modest weight loss (5-10%) is critical to alleviate the risk of any other metabolic disease. Reduced energy intake has been an essential factor for weight loss reduction. As a new behavior intervention to lose weight, intermittent fasting (IF) attracts considerable attention and has become a popular strategy among young people. IF is a diet pattern that cycles between periods of fasting and eating on a regular schedule, involving various types, mainly Intermittent Energy Restriction and Time-Restricted Fasting. Accumulating evidence shows that short-term IF has a greatly positive effect in animal studies and contributes favorable benefits in human trials as well. Nevertheless, as an emerging, diverse, and relatively premature behavior intervention, there are still limited studies considering patients with obesity and type 2 diabetes mellitus. It is also a controversial intervention for the treatment of metabolic disease and cancer. The risks and challenges appear consequently. Additionally, whether intermittent fasting can be applied to long-term clinical treatment, and whether it has side effects during the long-term period or not, demands more large-scale and long-term experiments.

Highly Stable and Eco-friendly Marine Self-Charging Power Systems Composed of Conductive Polymer Supercapacitors with Seawater as an Electrolyte.

A self-charging power system harvesting random and low-frequency wave energy into electricity provides a promising strategy for the construction of smart oceans. However, the system faces huge challenges of easy corrosion in the marine environment and the utilization of toxic organic electrolytes in energy storage devices. To address the issues above, a seawater supercapacitor (SWSC) for the marine self-charging power system is rationally proposed by using a conductive polymer, polypyrrole with hollow morphology (h-PPy), to enhance the stability and capacitance while using seawater as an eco-friendly electrolyte to reduce the cost and achieve sustainability. The hollow design provides a shortcut for the ion transportation of seawater into the h-PPy electrode, and the SWSC achieves a high power density of 4.32 kW kg-1 under an energy density of 5.12 W h kg-1. Even after 180 days in seawater, h-PPy still endows a mass retention of 99.9%, enabling the SWSC to maintain a stability of 99.3% after 6000 cycles. More importantly, when combined with a TENG module as the marine self-charging power system to harvest wave energy, the system provides a stable output in water wave to drive electronics and sensors, which shows a competitive potential in the smart ocean and marine internet of things.

Quantitative analysis of resveratrol derivatives in the seed coats of tree peonies and their hypoglycemic activities in vitro/vivo.

Tree peonies are well-known horticultural and medicinal plants. The tree peony seeds, as emerging woody oil crops, recently have attracted great attention for their metabolites and bioactivities. In this study, the phytochemicals isolated from tree peony seed coats were systematically investigated. Seven polyphenolics were separated and prepared, mainly belonging to resveratrol derivatives. There was a great variation in the seed coat polyphenolic content among eight Paeonia species, and the contents of the resveratrol trimers and dimers were significantly higher in the seed coats of Paeonia ostii than other species. Based on the HPLC fingerprint characteristics and chemometric analysis, a clear discrimination among Paeonia plants was found, including the composition patterns and contents of the constituents. Moreover, the characteristic phytochemicals (vateriferol and trans-ε-viniferin) could significantly reduce the starch-mediated levels of postprandial blood glucose in diabetic/normal mice. In addition, in vitro enzyme tests showed that the two compounds could effectively and competitively inhibit α-glucosidase, with the IC50 values of 3.01 and 7.75 µM, respectively, indicating that vateriferol and trans-ε-viniferin could be therapeutic potential agents for hyperglycemia and diabetes mellitus.

Dietary Fermented Soy Extract and Oligo-Lactic Acid Alleviate Chronic Kidney Disease in Mice via Inhibition of Inflammation and Modulation of Gut Microbiota.

Chronic kidney disease (CKD) is a global epidemic with an increasing prevalence worldwide. Effective preventive strategies are urgently needed. This study aimed to investigate the effect of nutraceutical components, a fermented soybean product (ImmuBalance, IMB) and an oligo-lactic acid product (LAP), on the prevention of adenine-induced CKD in mice. Female C57BL/6 mice were randomly assigned into following experimental groups: negative control; model control; and models treated with IMB at 250 or 1000 mg/kg body weight (BW), LAP at 1000 or 2000 mg/kg BW, and IMB/LAP combinations. The CKD model was established by intraperitoneal injection of adenine daily for 4 weeks, and treatments started 2 weeks before adenine injection and ended after 10 weeks. Compared with the model control, the treatments did not significantly alter the body weight or food intake. Both IMB and LAP, especially their combination, significantly inhibited tubular dilation, tubulointerstitial degeneration or atrophy, interstitial chronic inflammation and acute inflammation in the kidneys of CKD mice, and significantly decreased serum cystatin C levels. IMB or LAP significantly reversed CKD-associated increases of circulating and kidney levels of inflammatory cytokines, circulating levels of kidney injury biomarkers, and kidney levels of stem cell biomarkers, and significantly reversed CKD-associated reduction of cecum Clostridium leptum group. Our results suggest that dietary supplementation of IMB or LAP may significantly delay the development and/or progression of CKD.

Associations of C-reactive protein and fibrinogen with mortality from all-causes, cardiovascular disease and cancer among U.S. adults.

C-reactive protein (CRP) and fibrinogen are associated with an increased risk of death with suggested differences by gender, diet quality and race/ethnicity. However, the current evidence is limited. We used data including 8646 men and 9880 women from the National Health and Nutrition Examination Survey (NHANES) Linked Morality cohort (1999-2011) to investigate the associations of CRP and fibrinogen with mortality overall and by gender, race/ethnicity and diet quality. Cox-proportional hazard model was used to quantify the associations. With a median follow-up of 6 years, a strong dose-response relationship was observed between CRP levels and mortality risk in men after multivariable adjustment. For subjects who survived the first two years, the adjusted hazard ratios (HRs) for total mortality across quartiles (from lower to higher) of CRP were 1.97 (95% CI: 0.62-6.33), 1.89 (0.59, 6.06) and 6.34 (2.28-17.7) (P for trend <0.001). For cardiovascular disease (CVD) mortality, its association with CRP varied by diet quality. For cancer mortality, its association differed by history of cancer, and positive associations were observed only among subjects with history of cancer. In contrast, no such association of CRP with mortality was found in women. For fibrinogen, we observed its positive association with total mortality and the HRs across quartiles of fibrinogen (from lower to higher) were 1.21 (0.88, 1.67), 1.49 (1.22, 1.82) and 1.99 (1.56, 2.55). The association with CVD mortality differed by diet quality whereas no association was found with cancer mortality. Our findings suggest that higher levels of CRP and fibrinogen were associated with lower survival from total and CVD; the associations of CRP with mortality were more pronounced in men than women. Diet quality is an effect modifier for the association of CRP and fibrinogen with CVD mortality.

Attitudes towards HPV self-sampling among women in Chengdu, China: A cross-sectional survey.

OBJECTIVE: Cervical cancer screening participation in China remains insufficient, possibly because of embarrassment or discomfort. We assessed knowledge of HPV and its link to cervical cancer, and whether HPV self-sampling might be an acceptable alternative to clinician-based screening, among Sichuan women. METHODS: A sample of healthy women undergoing routine physical examinations in 2017 at the West China Hospital, Sichuan University, completed a questionnaire. RESULTS: From 3000 questionnaires distributed, 1810 were completed and analyzed. Only 29.94% of respondents (n = 542) had heard of HPV, among whom 65.75% knew that it caused cervical cancer. Among the 766 (42.32%) who considered that HPV self-sampling for cervical cancer screening was an acceptable option, over 90% thought it would be convenient, private, not embarrassing, and not painful. However, 1044 women (57.68%) did not consider self-sampling acceptable, mainly because the result might not be accurate (85.63%), specimens may have gone bad (83.05%), and they may not perform the test correctly (79.98%). Respondents who believed HPV self-sampling was acceptable were more likely than other respondents to be young, and to have completed at least secondary education. Of the 1810 respondents, 1312 (72.49%) reported that they would be willing to be vaccinated against HPV. CONCLUSION: Most women in Chengdu lack basic knowledge about HPV. Over 40% of women believed HPV self-sampling for cervical cancer screening was an acceptable option. To increase screening coverage, public health efforts to educate the public about HPV and HPV self-sampling for cervical cancer screening should be strengthened and expanded.

Generation of fully functional hepatocyte-like organoids from human induced pluripotent stem cells mixed with Endothelial Cells.

Despite advances in stem cell research, cell transplantation therapy for liver failure is impeded by a shortage of human primary hepatocytes (HPH), along with current differentiation protocol limitations. Several studies have examined the concept of co-culture of human induced pluripotent cells (hiPSCs) with various types of supporting non-parenchymal cells to attain a higher differentiation yield and to improve hepatocyte-like cell functions both in vitro and in vivo. Co-culturing hiPSCs with human endothelial cells (hECs) is a relatively new technique that requires more detailed studies. Using our 3D human embryoid bodies (hEBs) formation technology, we interlaced Human Adipose Microvascular Endothelial Cells (HAMEC) with hiPSCs, leading to a higher differentiation yield and notable improvements across a wide range of hepatic functions. We conducted a comprehensive gene and protein secretion analysis of our HLCs coagulation factors profile, showing promising results in comparison with HPH. Furthermore, a stage-specific glycomic analysis revealed that the differentiated hepatocyte-like clusters (HLCs) resemble the glycan features of a mature tissue rather than cells in culture. We tested our HLCs in animal models, where the presence of HAMEC in the clusters showed a consistently better performance compared to the hiPSCs only group in regard to persistent albumin secretion post-transplantation.

Distribution of high-risk HPV types among women in Sichuan province, China: a cross-sectional study.

BACKGROUND: Persistent infection with high-risk human papillomavirus (HR-HPV) is a major cause of cervical intraepithelial neoplasia and invasive cervical cancer. We investigated the prevalence of HR-HPV infection and distribution of viral genotypes among women in this area. METHODS: Women in Sichuan older than 20 years were screened for cervical cancer between January 2015 and December 2016 using liquid-based cytology testing and a flow cytometry-fluorescence hybridization test for HPV-DNA. Frequency tables were evaluated using the chi-squared test (χ2). RESULTS: Of the 17,319 women aged 20-85 years who participated in the study, Overall prevalence of HR-HPV infection was 12.6% (2178/17,319). The most prevalent viral type was HPV-52, which was present in 2.5% of individuals, followed by HPV-53 (1.6%), HPV-58 (1.5%), HPV-16 (1.1%), HPV-56 (0.9%), HPV-39 (0.8%). In HSIL, the five most common HR-HPV types were HPV52, 16, 58, 33 and 56. HPV16/18 in HSIL only makes up 25.9% of HSIL, whereas HPV31/33/45/52/58 make up 56.8%. Overall HR-HPV prevalence among women older than 65 years was 15.2%, significantly higher than the prevalence in other age groups (P < 0.05). Infection with dual or multiple HR-HPV types was associated with greater risk of abnormal cytology. CONCLUSION: Overall HR-HPV prevalence in Sichuan is as high as in large cities in China. The HR-HPV types 52, 16, 58, 33 and 56 predominated in this sample of HSIL women primarily from the banking and public sector in Sichuan. High prevalence among women older than 65 years needed pay attention to.

Radioprotective Effect of Walnut Oligopeptides Against Gamma Radiation-Induced Splenocyte Apoptosis and Intestinal Injury in Mice.

Walnut oligopeptides (WOPs) intake is associated with the augment of the antioxidant defense system and immune system. The chief object of this study is to evaluate the radioprotective effect of walnut oligopeptides extracted from walnut seed protein against 60Coγ-irradiation induced damage in mice. Female BALB/c mice were administered WOPs through drinking water for 14 days until a single dose of whole-body 60Coγ-irradiation. The 30-day survival test was carried out in the first group (8 Gy), and the other two groups (3.5 Gy) were sacrificed at 3 days and 14 days post-irradiation. Blood and organ samples of mice in the three groups were collected, the histopathological analysis and immunohistochemistry were conducted. The number of peripheral blood leukocytes, bone marrow DNA content, inflammatory cytokines, antioxidant capacity, and intestinal permeability were measured. We found that the administration of WOPs augmented antioxidant defense system, accelerated hematopoietic recovery and showed the significant trend toward higher survival rate and less weight loss compared with non-administrated control mice. In addition, WOPs administration appeared to be important to limit IR-induced splenocyte apoptosis and inflammatory cascade as well as reduce intestine epithelial barrier dysfunction and promote epithelial integrity. These results suggest that pre and post-treatment of WOPs may help to ameliorate acute damage, which is induced by ionizing radiation in mice and accelerate its recovery.

Ginseng oligopeptides protect against irradiation-induced immune dysfunction and intestinal injury.

Intestinal injury and immune dysfunction are commonly encountered after irradiation therapy. While the curative abilities of ginseng root have been reported in prior studies, there is little known regarding its role in immunoregulation of intestinal repairability in cancer patients treated with irradiation. Our current study aims to closely examine the protective effects of ginseng-derived small molecule oligopeptides (Panax ginseng C. A. Mey.) (GOP) against irradiation-induced immune dysfunction and subsequent intestinal injury, using in vitro and in vivo models. Expectedly, irradiation treatment resulted in increased intestinal permeability along with mucosal injury in both Caco-2 cells and mice, probably due to disruption of the intestinal epithelial barrier, leading to high plasma lipopolysaccharide (LPS) and pro-inflammatory cytokines levels. However, when the cells were treated with GOP, this led to diminished concentration of plasma LPS and cytokines (IL-1 and TNF-α), suggesting its dampening effect on inflammatory and oxidative stress, and potential role in restoring normal baseline intestinal permeability. Moreover, the Caco-2 cells treated with GOP showed high trans-epithelial electrical resistance (TEER) and low FITC-dextran paracellular permeability when compared to the control group. This could be explained by the higher levels of tight junction proteins (ZO-1 and Occludin) expression along with reduced expression of the apoptosis-related proteins (Bax and Caspase-3) noticed in the GOP-treated cells, highlighting its role in preserving intestinal permeability, through prevention of their degradation while maintaining normal levels of expression. Further confirmatory in vivo data showed that GOP-treated mice exhibited high concentrations of lymphocytes (CD3+, CD4+, CD8+) in the intestine, to rescue the irradiation-induced damage and restore baseline intestinal integrity. Therefore, we propose that GOP can be used as an adjuvant therapy to attenuate irradiation-induced immune dysfunction and intestinal injury in cancer patients.

Knowledge of HPV and acceptability of HPV vaccine among women in western China: a cross-sectional survey.

BACKGROUND: Since most cervical cancer cases are caused by persistent high-risk human papillomavirus (HR-HPV) infection, knowledge of HPV among women is essential for the prevent of cervical cancer. This study was aimed to assess knowledge among women in western China about HPV and its association with cervical cancer, and to assess their acceptance of HPV vaccination. METHODS: A sample of healthy women undergoing routine physical examinations in the Health Management Center of West China Hospital, Sichuan University between January and December 2014 completed a questionnaire. RESULTS: A total of 1300 questionnaires were distributed, and 1109 were completed and analyzed. Only 28.85% of respondents (n = 320) had heard of HPV; among this subgroup, only half (53.44%) knew that it causes cervical cancer, only 26 (8.13%) correctly answered all questions about HPV. Multivariate analysis showed that respondents who had heard of HPV were more likely than other respondents to have a family history of any cancer, to undergo regular Pap tests and to have completed at least secondary education. Half of all respondents (51.22%) reported that they would be willing to be vaccinated against HPV. CONCLUSION: Although most women in western China lack basic knowledge about HPV, at least half are willing to take the HPV vaccine. Public health efforts to educate the public about HPV and its connection to cervical cancer should be strengthened and expanded.

Ginseng (Panax ginseng Meyer) oligopeptides regulate innate and adaptive immune responses in mice via increased macrophage phagocytosis capacity, NK cell activity and Th cells secretion.

Traditionally used as a restorative medicine, ginseng (Panax ginseng Meyer) has been the most widely used and acclaimed herb in Chinese communities for thousands of years. To investigate the immune-modulating activity of ginseng oligopeptides (GOP), 420 healthy female BALB/c mice were intragastrically administered distilled water (control), whey protein (0.15 g per kg body weight (BW)), and GOP 0.0375, 0.075, 0.15, 0.3 and 0.6 g per kg BW for 30 days. Blood samples from mice were collected from the ophthalmic venous plexus and then sacrificed by cervical dislocation. Seven assays were conducted to determine the immunomodulatory effects of GOP on innate and adaptive immune responses, followed by flow cytometry to investigate spleen T lymphocyte sub-populations, multiplex sandwich immunoassays to investigate serum cytokine and immunoglobulin levels, and ELISA to investigate intestinally secreted immunoglobulin to study the mechanism of GOP affecting the immune system. Our results showed that GOP was able to enhance innate and adaptive immune responses in mice by improving cell-mediated and humoral immunity, macrophage phagocytosis capacity and NK cell activity. Notably, the use of GOP revealed a better immune-modulating activity compared to whey protein. We conclude that the immune-modulating activity might be due to the increased macrophage phagocytosis capacity and NK cell activity, and the enhancement of T and Th cells, as well as IL-2, IL-6 and IL-12 secretion and IgA, IgG1 and IgG2b production. These results indicate that GOP could be considered a good candidate that may improve immune functions if used as a dietary supplement, with a dosage that ranges from 0.3 to 0.6 g per kg BW.

Suppression of TNF-α and free radicals reduces systematic inflammatory and metabolic disorders: Radioprotective effects of ginseng oligopeptides on intestinal barrier function and antioxidant defense.

Irradiation therapy is markedly associated with intestinal injure and oxidant stress. This study aimed to investigate the effects of ginseng (Panax ginseng C.A. Mey.) oligopeptides (GOP) on irradiation-induced intestinal injury and antioxidant defense in mice. BALB/c mice (8 weeks old) were randomly divided into six groups: vehicle control, irradiation control (IR), IR+whey protein [0.30 g/kg body weight (BW)], IR+GOP 0.15 g/kg BW, IR+GOP 0.30 g/kg BW and IR+GOP 0.60 g/kg BW. Postirradiation 30-day survival trial, white blood cells count and bone marrow hematopoietic system damage were performed to identify the injury degree induced by irradiation. Then, histopathology analysis was observed and intestinal permeability in vivo was quantified with fluorescein isothiocyanate-dextran. The enzyme-linked immunosorbent assay was used to determine antioxidant ability, plasma inflammatory cytokines, diamine oxidase (DAO) and endotoxin (LPS) levels. The immunohistochemistry assay was used to analyze the expression levels of tight junction proteins. We found that GOP-treated mice exhibited lower concentrations of plasma LPS and DAO and decreased instructors of inflammatory and oxidative stress which were linked to the lower intestinal permeability and higher tight junction proteins expression. The blockage of GOP was linked with the reduction of TNF-α and free radicals. The 15-day pretreatment of GOP could exhibit radioprotective effects, and another 15-day posttreatment benefited the quick repair of irradiation-induced injury. We confirm that GOP would exhibit effective therapeutic value on attenuating irradiation-induced hematopoietic, gastrointestinal and oxidative injury in cancer patients.

Sea cucumber (Codonopsis pilosula) oligopeptides: immunomodulatory effects based on stimulating Th cells, cytokine secretion and antibody production.

This study aimed to investigate the immunomodulating activity of small molecule oligopeptides from sea cucumber (Codonopsis pilosula) (SOP) in mice. Seven assays were performed to determine the immunomodulatory effects, including splenic lymphocyte proliferation and delayed-type hypersensitivity assays (cell-mediated immunity), IgM antibody response of spleen to sheep red blood cells (SRBC) and serum hemolysin level assays (humoral immunity), the carbon clearance assay and the phagocytic capacity of peritoneal cavity phagocytes assay (macrophage phagocytosis), and the NK cell activity assay. Spleen T lymphocyte subpopulations, multiplex sandwich immunoassays of serum cytokine and immunoglobulin levels and enzyme-linked immunosorbent assays for small intestinal secretory immunoglobulin were performed to study the mechanism by which SOP affects the immune system. We found that SOP could improve immune functions in mice, which may be due to the enhancement of the functions of cell-mediated immunity, humoral immunity, macrophage phagocytosis and NK cell activity. From the cellular and molecular assays, we postulated that the immunomodulatory effects are most likely attributed to the stimulation of Th cells, cytokine secretion and antibody production.

[Expression of miR-429 and Its Target Gene HSPA4L in Sperms from Asthenospermia Patients.]

OBJECTIVES: To investigate the expression of miR-429 and its target gene heat shock protein A4L (HSPA4L) in sperms from asthenospermia patients. METHODS: Twenty semen samples from healthy and fertile adults and 20 semen samples from asthenospermia patients were collected,and normal sperm parameters were defined according to World Health Organization criteria.The expression levels of miR-429 and HSPA4L mRNA were determined by qRT-PCR,and the bioinformatics tool (Targetscan) was used to predict the target of miR-429.Luciferase reporter assay and transfection study were performed to confirm target gene of miR-429.The expression levels of HSPA4L mRNA and protein were further determined by qRT-CPR and Western blot,respectively. RESULTS: The motility and viability of sperms from asthenospermia patients were lower than that in control group,and miR-429 was up-regulated in sperms from asthenospermia patients.Bioinformatics analysis revealed that HSPA4L was a target of miR-429.Luciferase reporter assay and transfection study further confirmed that miR-429 suppresses the expressions of HSPA4L mRNA and protein via directly targeting HSPA4L 3'UTR.Results from clinical samples also demonstrated that HSPA4L mRNA and protein were down-regulated in sperms from asthenospermia patients and the expression level of miR-429 was inversely correlated with the expression level of HSPA4L mRNA (r=-0.725, P<0.05). CONCLUSIONS: miR-429 is up-regulated in sperms from asthenospermia patients,and it may modulate the motility and viability of sperms via suppressing the expression of HSPA4L.

Expression of VEGF-D in epithelial ovarian cancer and its relationship to lymphatic metastasis.

AIM: To investigate the contribution of vascular endothelial growth factor (VEGF)-D to tumor progression, tumor lymphangiogenesis and lymphatic metastasis in epithelial ovarian cancer. METHODS: The expression profiles of VEGF-D in 18 benign, 14 borderline and 87 malignant epithelial ovarian cancers were examined using immunohistochemical (IHC) staining. Lymphatic vessels were identified using IHC staining on lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), which is a lymph-specific receptor for hyaluronan in identifying lymphatic vessels. The potential correlation among VEGF-D, lymphatic vessel density (LVD) and clinico-pathological factors of the epithelial ovarian cancer was also analyzed. RESULTS: Positive IHC staining of VEGF-D was observed in 17% of benign, 21% of borderline and 80% of malignant epithelial ovarian tumors specimens. In the epithelial ovarian cancer specimens, the LVD was 3.41 ± 2.37 in the VEGF-D negative (17 patients), 5.42 ± 3.49 in the weak (26 patients), 7.22 ± 2.36 in the moderate (27 patients) and 7.35 ± 4.06 in the strong (17 patients) groups, respectively. Additionally, the expression of VEGF-D was positively correlated with LVD (r = 0.415, P < 0.001). The expression level of VEGF-D was significantly higher in lymph node-positive epithelial ovarian cancer than in lymph node-negative patients (P = 0.009, P < 0.05). The expression of VEGF-D was significantly correlated with lymph node metastasis, International Federation of Gynecology and Obstetrics stage and tumor histological differentiation, but not with the patients' age or histology type. CONCLUSION: VEGF-D may play an important role in the process of lymphatic metastasis of epithelial ovarian cancer.