Oxyresveratrol, a Stilbene Compound from Morus alba L. Twig Extract Active Against Trichophyton rubrum.

Morus alba L. (mulberry) twig is known to have an inhibitory effect on pathogens in traditional Chinese medicine. In the present study, the dermophytic fungus, Trichophyton rubrum, was used to evaluate the inhibitory effect of total M. alba twig extract and extracts obtained using solvents with different polarities by the method of 96-well MTT colorimetry. The main active substance was isolated and identified by tracking its activity. In addition, the inhibitory effects of active extracts and a single active substance were investigated in combination with miconazole nitrate. Our data indicated that ethyl acetate extracts of mulberry twig (TEE) exhibited a desired inhibitory activity on T. rubrum with the minimum inhibitory concentration (MIC) of 1.000 mg/mL. With activity tracking, the main substance showing antimicrobial activity was oxyresveratrol (OXY), which was isolated from TEE. Its MIC for inhibiting the growth of T. rubrum was 0.500 mg/mL. The combined use of miconazole nitrate and OXY showed a synergistic inhibitory effect, as shown by a significant decrease in the MIC of both components. Based on the OXY content in TEE, the contribution rate of OXY to the inhibitory effect of TEE on T. rubrum was 80.52%, so it was determined to be the main antimicrobial substance in M. alba twig. Copyright © 2017 John Wiley & Sons, Ltd.

[Effect of Land Use on the Stability of Soil Organic Carbon in a Karst Region].

The composition of soil organic carbon and its stability mechanism are the key to understanding the terrestrial carbon sink capacity. The stability of soil organic carbon in a karst ecosystem greatly affects the soil carbon fixation capacity. In order to understand the impact of human activities on the stability of soil organic carbon in karst areas, the karst valley area of Zhongliang Mountain in Chongqing was selected as an example, and soil samples of four typical land use modes (mixed forest, bamboo forest, grassland, and cultivated land) were collected in layers to analyze the total organic carbon (TOC) and heavy fraction organic carbon (HFOC). The distribution characteristics of light fraction organic carbon (LFOC), labile organic carbon (LOC), and recalcitrant organic carbon (ROC) were analyzed quantitatively by using a structural equation model to provide basic data for soil carbon sink assessment and soil quality protection in karst areas. The results showed that the organic carbon components under different land use patterns in karst areas had obvious surface accumulation, and the content of organic carbon components in the surface layer was 1.2 times that in the bottom layer. Except for LFOC, the content of other organic carbon components was the highest in the mixed forest, followed by that in the bamboo forest and wasteland, with the lowest in cultivated land. Mixed forest ω(TOC) content was the highest, 42.5 g·kg-1, followed by that of bamboo forest (36.6 g·kg-1) and grassland (18.7 g·kg-1), and cultivated land content was the lowest, 13.4 g·kg-1. The soil organic carbon content of cultivated land was 68.5%, 63.5%, and 28.3% lower than that of mixed forest, bamboo forest, and grassland, respectively. Mixed forest had the highest content of ω(HFOC), 21 g·kg-1, followed by those of bamboo forest (20.9 g·kg-1), grassland (18.2 g·kg-1), and cultivated land (13.5 g·kg-1). The mixed forest ω(LOC) content was the highest, 16.3 g·kg-1, followed by those of bamboo forest (14.9 g·kg-1), grassland (11.5 g·kg-1), and cultivated land (5.3 g·kg-1). Mixed forest ω (ROC) content was the highest, 25.7 g·kg-1, followed by those of bamboo forest (21.6 g·kg-1), grassland (15.9 g·kg-1), and cultivated land (10.3 g·kg-1). The bamboo forest land ω(LFOC) content was 15.9 g·kg-1, followed by those of mixed forest (13.9 g·kg-1), grassland (7.3 g·kg-1), and cultivated land (4.9 g·kg-1). The recalcitrant organic carbon index (ROCI) was used to indicate the stability of soil organic carbon. The variation range of ROCI was 33.9%-64.5%, of which the highest was mixed forest (64.5%-66.3%), and the lowest was cultivated land (33.8%-39.6%). The ROCI of mixed forest, bamboo forest, and grassland were 1.8 times, 1.6 times, and 1.4 times that of cultivated land, respectively. Karst area ω (inert organic carbon) content and ROCI showed that human agricultural activities caused the reduction in soil organic carbon content and the destruction of soil physical structure, resulting in the accelerated decomposition and turnover rate of soil organic matter. The most important factor affecting soil stability in karst areas was soil pH. Tillage activities caused soil pH to rise, reduced soil microbial activity, and were not conducive to the accumulation of the inert organic carbon and soil organic carbon pool in the soil.

[Effects of Land Use Change on Soil Aggregate Stability and Soil Aggregate Organic Carbon in Karst Area of Southwest China].

Investigating the relationship of soil aggregate stability with the organic carbon in the aggregate and its response to land use change is conducive to the estimation of soil carbon sink potential, improvement of rocky desertification, and rational land use in karst areas of Southwest China. In order to explore the effects of land use change on the composition and stability of soil aggregate stability as well as the content of aggregate organic carbon, the soil (0-30 cm) of five land use types (secondary forest, pomelo forest, paddy field, pepper forest, and dry land) was selected as the research object. The characteristics and correlation of soil aggregate components and organic carbon under different land use patterns were obtained, and the contribution of soil aggregates to the change in organic carbon after land use change was calculated. The results showed that the macroaggregates in the surface soil (0-15 cm) of the secondary forest, pomelo forest, and paddy field were 63.32%, 52.38%, and 47.77%, respectively, which were significantly higher than that of dry land (23.70%), as was also seen in the lower layer (15-30 cm). The geometric mean diameter (GMD) and mean weight diameter (MWD) of soil aggregates in the secondary forest, pomelo forest, and paddy field were significantly higher than those in dry land. In the surface soil, the organic carbon of the secondary forest and paddy field was significantly higher than that of other land use patterns. By contrast, in the lower soil layer, only the organic carbon of the paddy field was significantly higher than that of the others. Under different land use patterns, the organic carbon content of aggregates followed the same order of macroaggregates > microaggregates > silt and clay, indicating that macroaggregates allowed soil organic carbon to accumulate, whereas silt and clay did the opposite. According to correlation analysis, the content of soil macroaggregates was significantly positively correlated with GMD, MWD, and soil aggregate organic carbon, suggesting that the increase in soil macroaggregates could improve the stability of soil aggregates and store more soil organic carbon. Further, as land use change may have significantly affected the soil aggregate, moderate development of forestry and paddy cultivation is suggested to improve the soil carbon sequestration potential in the karst area of Southwest China.

Individualized management of immunosuppressants in liver transplant recipients by using a novel immune score system.

BACKGROUND: There is no reliable means to evaluate the immune status of liver transplant recipients. We proposed a novel score model, namely Mingdao immune cell analysis and Mingdao immune score system, to quantify the immunity. METHODS: Data from those who underwent a single liver transplant between January 2017 and June 2020 at Beijing Chaoyang Hospital, were collected. In addition, healthy volunteers were also enrolled. The score model was based on the immune cell populations determined by flow cytometry. RESULTS: There were a total of 376 healthy controls with 376 tests and 148 liver transplant recipients with 284 tests in this study. Evaluated by Mingdao immune cell analysis and Mingdao immune score system, the mean scores of healthy controls were near zero suggesting a balanced immune system. In contrast, the mean scores of liver transplant recipients were negative both before and after surgery indicating a compromised immune system. When liver transplant recipients were given a reduced or routine first dose according to their preoperative score, they had similar recovery of liver function. Moreover, liver transplant recipients with increased scores ≥ 5 were associated with elevated aspartate transaminase and alanine amiotransferase. Finally, on multivariate analysis the score model was the only significant independent risk factor for clinical acute rejection (P = 0.021; Odds ratio, 0.913; 95% confidence interval, 0.845-0.987). CONCLUSION: The novel score model could be used as an indicator to reflect immunity and to regulate immunosuppressants in liver transplant recipients after surgery.

Impact of metabolic dysfunction-associated fatty liver disease on liver transplant recipients with hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease was proposed by international consensus to redefine the metabolic abnormal condition. However, its impact on liver transplant recipients with hepatitis B virus-related hepatocellular carcinoma has not been explored. METHODS: A two-center retrospective cohort study on liver transplant recipients with hepatitis B virus-related hepatocellular carcinoma was performed to analyze the impact of metabolic dysfunction-associated fatty liver disease on the clinicopathologic parameters and prognosis. RESULTS: There were 201 liver transplant recipients enrolled from two hospitals in our study. The pre- and post-transplant prevalences of metabolic dysfunction-associated fatty liver disease were 9.95% and 28.86%, respectively. The clinicopathological parameters revealed a similarity between patients with and without pre-transplant metabolic dysfunction-associated fatty liver disease. In contrast, the group with post-transplant metabolic dysfunction-associated fatty liver disease was linked with older age, a higher hepatitis recurrence rate and incidence of cardiovascular disease, usage of calcineurin inhibitors, a greater body mass index and waist circumference, lower albumin and high-density lipoprotein cholesterol levels, and poorer tumor-free survival and overall survival. The multivariate analysis showed the largest tumor size >4 cm (95% confidence intervals: 0.06~0.63, p = 0.006), microvascular invasion (95% confidence intervals: 1.61~14.92, p = 0.005), post-transplant metabolic dysfunction-associated fatty liver disease (95% confidence intervals: 1.40~10.60, p = 0.009), and calcineurin inhibitors-based regimen (95% confidence intervals: 0.33~0.96, p = 0.036) were the independent risk factors for recurrent hepatocellular carcinoma. CONCLUSIONS: Our study suggests that post-transplant metabolic dysfunction-associated fatty liver disease is more closely to metabolic abnormalities and that it can help identify liver transplant recipients at high risk of recurrent hepatocellular carcinoma.

Plasmacytoid dendritic cells mediate the tolerogenic effect of CD8+regulatory T cells in a rat tolerant liver transplantation model.

BACKGROUND: Tolerance is more easily induced in liver transplant models than in other organs; CD8+CD45RClowregulatory T cells (Tregs) have been shown to induce tolerance in heart allografts. Whether CD8+CD45RClowTregs could induce tolerance in a liver transplant model and how dendritic cells (DCs) mediate the CD8+CD45RClowTregs effect remains to be investigated. METHODS: A rat liver transplantation model was established and used to test tolerance and acute rejection compared to control groups. Liver function and histopathological changes of allograft were examined by enzyme-linked immunosorbent assay (ELISA) and haematoxylin and eosin (H&E) staining, respectively. The distribution and proportion of CD8+CD45RClowTregs and plasmacytoid dendritic cells (pDCs) in the allografts and spleen were determined using flow cytometry. Cytokine secretion levels were determined using ELISA and real-time quantitative PCR (qRT-PCR). RESULTS: The rat liver transplantation model was well established, with a success rate of 93.3% (28/30). The mean survival time of the tolerant and acute-rejection rats were 156 and 14 days, respectively. The proportions of CD8+CD45RClowTegs were higher in the allografts of tolerant rats than in those of acute-rejection rats (33.1 ± 4.3 and 12.4 ± 4.6, respectively; P = 0.04). Significant accumulation of pDCs was observed in tolerant liver graft rats compared to that in acute-rejection rats (1.46 ± 0.23 and 0.80 ± 0.20, respectively; P = 0.02). Importantly, CD8+CD45RClowTregs were positively associated with the frequency of pDCs (P = 0.001, r2 = 0.775). The protein and mRNA expression of IL-10 and TGF-ß in the allograft group were increased, possibly being responsible for tolerance induction. CONCLUSION: CD8+CD45RClowT cells interact with pDCs through the induction of IL-10 and TGF-ß expression and are responsible for inducing immune tolerance in rat liver transplantation.

Association between antiplatelet medication and cerebral microbleeds in stroke-free population.

BACKGROUND: Cerebral microbleeds (CMBs) may increase the risk of future intracerebral hemorrhage and ischemic stroke. However, It is unclear whether antiplatelet medication is associated with CMBs. This study aimed to investigate the association between antiplatelet medication and CMBs in a community-based stroke-free population. METHODS: In this cross-sectional study, stroke-free participants aged 18-85 years were recruited from a community in Beijing, China. Demographic, clinical, and antiplatelet medication data were collected through a questionnaire, and all participants underwent blood tests and brain magnetic resonance imaging at 3.0T. The presence, count, and location of CMBs were evaluated using susceptibility-weighted imaging. The association between antiplatelet medication and the presence of CMBs was analyzed using multivariable logistic regression. The associations between antiplatelet medication and CMBs by location (lobar, deep brain or infratentorial, and mixed regions) were also analyzed using multinomial logistic regression. A linear regression analysis was conducted to determine the association between antiplatelet medication and the log-transformed number of CMBs. RESULTS: Of the 544 participants (mean age: 58.65 ± 13.66 years, 217 males), 119 participants (21.88%) had CMBs, and 64 participants (11.76%) used antiplatelet medication. Antiplatelet medication was found to be associated with CMBs at any location [odds ratio (OR) = 2.39, 95% CI: 1.24-4.58] and lobar region (OR = 2.83, 95% CI: 1.36-5.86), but not with the number of CMBs (ß = 0.14, 95% CI: -0.21-0.48). Among antiplatelet medications, aspirin use was found to be associated with any CMB (OR = 3.17, 95% CI: 1.49-6.72) and lobar CMBs (OR = 3.61, 95% CI: 1.57-8.26). CONCLUSIONS: Antiplatelet medication was associated with CMBs in stroke-free participants, particularly lobar CMBs. Among antiplatelet medications, aspirin use was associated with any CMB and lobar CMBs. Our findings suggest that it might be essential to optimize the management of antiplatelet medication in the stroke-free population with a higher burden of vascular risk factors to reduce the potential risk of CMBs.

Time-dependent reactive oxygen species inhibit Streptococcus mutans growth on zirconia after a helium cold atmospheric plasma treatment.

As an efficient strategy for the modification of material surfaces, cold atmospheric plasma (CAP) has been used in dentistry to improve hard and soft tissue integration of dental implant materials. We previously found the Streptococcus mutans growth was inhibited on the surface of zirconia implant abutment after a 60-second helium cold atmospheric plasma treatment. However, the mechanism of bacterial growth inhibition on CAP-treated zirconia has not been fully understood. The duration of bacterial inhibition effectiveness on CAP-treated zirconia has also been insufficiently examined. In this work, we assume that reactive oxygen species (ROS) are the primary cause of bacterial inhibition on CAP-treated zirconia. The ROS staining and an ROS scavenger were utilized to evaluate the bacterial intracellular ROS level, and to determine the role of ROS in bacterial growth inhibition when seeded on CAP-treated zirconia. The time-dependent effectiveness of CAP treatment was determined by changes in surface characteristics and antibacterial efficacy of zirconia with different storage times after CAP treatment. This study confirmed that the presence of reactive oxygen species on the zirconia surface after CAP treatment inhibits the growth of Streptococcus mutans on the material surface. Although the antibacterial efficacy of the 60-second CAP-treated zirconia decreased over time, there were fewer bacteria on the treated surface than those on the untreated surface after 14 days.

The Model for End-Stage Liver Disease Score and the Follow-Up Period Can Cause the Shift of Circulating Lymphocyte Subsets in Liver Transplant Recipients.

Little is known about the shift of lymphocytes under the condition of the model for end-stage liver disease score and the follow-up period. Then, we detected the peripheral blood from liver transplant recipients by flow cytometry and compared the results. The model for end-stage liver disease score affected the percentages of T-cell subsets and B cells during the short-term follow-up period, but failed to influence the lymphocyte subsets during the long-term follow-up period. In contrast, the follow-up period not only affected the absolute counts of T-cell subsets and natural killer (NK) cells in patients with the low model for end-stage liver disease scores, but also influenced the percentages and absolute counts of T-cell subsets in patients with the high model for end-stage liver disease scores. In the two-way ANOVA, we further revealed that the model for end-stage liver disease score was associated with the percentages of T cells and CD4+ T cells and the absolute numbers of T-cell subsets and B cells, while the follow-up period was associated with the percentages of T-cell subsets and the absolute numbers of lymphocyte subsets. Therefore, patients with either the low model for end-stage liver disease scores or the long-term follow-up period are in a relatively activated immune condition.

Decreased granzyme B+CD19+B cells are associated with tumor progression following liver transplantation.

Lymphocytes play an important role in antitumor immunity following organ transplantation. However, the function of granzyme B+CD19+B cells on the hepatocellular carcinoma cells from liver transplant recipients remains largely unknown; we aimed to analyze the function and elucidate the mechanisms behind it. Blood samples and clinical data from liver transplant recipients and healthy controls at Beijing Chaoyang Hospital as well as from a validation cohort were collected and analyzed. In this study, we found decreased granzyme B+CD19+B cells were correlated with early hepatocellular carcinoma recurrence and could further identify liver transplant recipients with poor tumor differentiation, microvascular invasion, increased total tumor diameter, and tumor beyond Milan criteria. Notably, granzyme B+CD19+B cells directly inhibited the proliferation, migration, and invasion of hepatocellular carcinoma cells. Upon activation regulatory B cells from liver transplant recipients with hepatocellular carcinoma recurrence displayed a CD5+CD38+CD27+CD138+CD19+ granzyme B+ phenotype, but the increased expression of CD5, CD38, and CD138, and the decreased protein level and transcriptional level requiring JAK/STAT signaling. In an independent validation cohort, liver transplant recipients with decreased granzyme B+CD19+B cells had not only early hepatocellular carcinoma cell recurrence but also shorter survival. Our study provides comprehensive data from liver transplant recipients with hepatocellular carcinoma, indicating a critical role of granzyme B+CD19+B cells in preventing cancer progression. Our findings warrant further investigations for the design of future immunotherapies leading to immune responses and improved patient survival.

Birth experiences of urban women of advanced age having their second child after introduction of the universal two-child policy in China: A qualitative study.

OBJECTIVE: to investigate the birth experiences of women of advanced age having a second child in urban China after introduction of the universal two-child policy in 2016. DESIGN: data were collected using semi-structured in-depth interviews, and were processed and analysed using a qualitative phenomenological method. SETTING: obstetric department of a class 1, level 3 hospital in Henan Province, China. PARTICIPANTS: purposive sampling was undertaken, and 11 hospitalized women from urban backgrounds were selected as the participants. They were all aged >35 years and were having their second child. The interviews were conducted 2-4 days post partum. FINDINGS: the findings were divided into four themes: motives for the birth of a second child; anticipations for the child's gender; difficulty in conceiving; and conflicts after birth. The main reason for having a second child was no longer in accordance with the traditional Chinese mindset to 'raise sons to secure a happy life when one gets old'; instead, it was to secure family balance and harmony to respond to the new policy. Educated women from urban backgrounds were able to accept the gender of the second child 'as it came', without the old mindset that 'men are superior to women' and 'only boys can carry on family lines'. Advanced maternal age and gestational complications were the major difficulties facing these women. Chinese medicine and regimens were recognised as effective and conducive. Following the birth of their second child, the women experienced both positive feelings (joy due to the arrival of the new baby) and negative feelings (pressures and challenges on family finances, demands for more living space, and balancing their affections between two children). CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: women of advanced age who choose to have a second child have sensible motives and, for the most part, their experience is positive. That said, the participants faced and overcame many difficulties before, during and after the birth of their second child. They were in need of help from the government and their employers in terms of policy, and proper education on care-taking and recuperation from medical professionals. Families who have a second child should treat the second child calmly and with common sense, make quick adjustments to family structural changes, and strike a proper balance in an effort to divide love and care equally between the two children.

[Residual Characteristics and Health Assessment Analysis of OCPs and PCBs in Karst Groundwater].

Residual levels of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in karst groundwater in Nanshan Laolongdong were measured using a gas chromatograph equipped with a micro-63Ni electron capture detector to determine the residual characteristics including concentration, distribution, and source of OCPs and PCBs. Results revealed that the total concentration range of OCPs was 34.8-623.2 ng·L-1, and the mean value was 215.6 ng·L-1, among which the total concentration ranges of HCHs, DDTs, and other OCPs were 8.2-23.6, 4.5-363.7, and 22.2-235.9 ng·L-1, respectively, and the mean values were 15.9, 104.5, and 95.3 ng·L-1; the total concentration range of PCBs was 6.0-40.7 ng·L-1, and the mean value was 16.8 ng·L-1. Overall, the pollution of OCPs and PCBs was above average; the results of multiple comparisons revealed that statistically significant differences occurred in the concentration of some OCPs and PCBs. The pollution levels in the water of each sampling point in the study area were quite different; however, the seasonal distribution of OCPs and PCBs was relatively uniform. Source analyses revealed that HCHs' source was the input of lindane in the surrounding environment, DDTs recently originated from illegal use of industrial DDT, other OCPs originated from atmospheric deposition and agricultural input, and PCBs' sources included both historical remains and enterprise production processes. The results of Pearson correlation analyses revealed that some organo-halogen pollutants were homologous or had similar sources and decomposition mechanisms. According to health risk assessment model, drinking water in the study area would not cause obvious harm to human health, but children were more sensitive to pollutants than adults.

C­type natriuretic peptide prevents angiotensin II­induced atrial connexin 40 and 43 dysregulation by activating AMP­activated kinase signaling.

C­type natriuretic peptide (CNP), from the family of natriuretic peptides (NPs), has been shown to induce antihypertrophic and antifibrotic effects in cardiomyocytes. However, the roles of CNP in the atrial dysregulation of connexin (Cx)40 and Cx43 remain to be elucidated. The present study aimed to investigate the effects of CNP on angiotensin (Ang) II­induced Cx40 and Cx43 dysregulation in isolated perfused beating rat left atria. A rat isolated perfused beating atrial model was used and the protein levels were determined via western blotting. Ang II significantly upregulated NF­κB, activator protein­1, transforming growth factor­ß1 (TGF­ß1), collagen I and matrix metalloproteinase 2, leading to atrial fibrosis, and downregulated expression of Cx40 and Cx43. The changes in Cx40 and Cx43 induced by Ang II were abolished by CNP through upregulation of phosphorylated AMP­activated kinase a1 (AMPK) and downregulation of TGF­ß1. The effects of CNP on AMPK and TGF­ß1 levels were inhibited by KT5823 and pertussis toxin, inhibitors of protein kinase G (PKG) and NP receptor type C (NPR­C), respectively. Thus, CNP can prevent Ang II­induced dysregulation of Cx40 and Cx43 through activation of AMPK via the CNP­PKG and CNP­NPR­C pathways in isolated beating rat atria. The present findings suggested that CNP may be therapeutically useful for clinical conditions involving cardiac dysregulation of Cx expression­related diseases.

Comparison of the Hepatoprotective Effects of the Three Main Stilbenes from Mulberry Twigs.

The purpose of this study was to compare the hepatoprotective effects of Oxy (oxyresveratrol), Res (resveratrol), and MulA (mulberroside A) (80 mg/kg body weight/d, i.g.) on acute liver injury (ALI) induced by lipopolysaccharide (LPS)/d-galactosamine (d-GalN) in mice. After 7 h of LPS (50 µg/kg body weight, i.p.) and d-GalN (500 mg/kg body weight, i.p.) exposure, the activities of serum transaminases and antioxidant enzymes were determined. The expressions of the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway, the nuclear factor-kappa B (NF-κB) signal pathway, and the mitogen-activated protein kinase (MAPK) signal pathway related proteins were evaluated by Western blot assays. Histopathological analysis was performed by hematoxylin-eosin (H&E) staining on the separated livers of mice. The results showed that treatment with Oxy, Res, and MulA could significantly decreases the levels of alanine transaminase (ALT) and aspartate transaminase (AST) ( P < 0.01). MulA was the most effective ingredient among the three, and the ALT and AST levels were reduced at 90.3 ± 1.3% and 93.9 ± 1.1% compared with the LPS/D-GalN treated group ( P < 0.01). Meanwhile, the stilbenes curbed the expression of inflammatory factors, NF-κB pathway activation, and MAPKs phosphorylation and upregulated antioxidant enzymes, Nrf2, NAD (P) H:quinone oxidoreductase (NQO1), and heme oxygenase-1 (HO-1) expression levels. Stilbenes might protect the ALI caused by LPS/d-GalN through inhibiting the negative effectiveness of oxidation stress and inflammation. The protective performance of MulA was better than those of Oxy and Res, and we hypothesize that it might be due to the mediation of the specific metabolic pathway of the MulA in vivo. All of these results implied that stilbenes in mulberry twigs might be promising as natural additives.

Epstein-Barr virus-encoded LMP1 regulated Pim1 kinase expression promotes nasopharyngeal carcinoma cells proliferation.

BACKGROUND: Epstein-Barr virus-encoded LMP1 plays a critical role in the carcinogenesis of nasopharyngeal carcinoma (NPC), but the mechanism remains elusive. We aimed to analyze the expression and clinical pathological significance of provirus integration site for Moloney murine leukemia virus 1 (Pim1) in clinical NPC, and to elucidate the effect of LMP1 on Pim1 expression and its mechanism. METHODS: Immunohistochemical staining was used to detect the expression of Pim1 in clinical NPC tissues and control nasopharyngeal chronic inflammation (NPI) tissues, and the correlation between Pim1 and clinical parameters of NPC patients was analyzed. The LMP1 stable expression cell line CNE1-LMP1-OV was constructed through infecting the well-differentiated nasopharyngeal carcinoma cells CNE1 with LMP1 overexpressing lentivirus. Then the in vivo experiments were conducted. RESULTS: Among 89 NPC patients, 48 cases (53.93%) were positive for Pim1, while only one case was Pim1 positive in 15 NPI controls (6.67%). Pim1 expression was not correlated with gender, age, smoking status and clinical classification of NPC patients, but positively correlated with T, N and M classification. CNE1-LMP1-OV cell line was successfully established, which displayed a higher cell proliferation ability and Pim1 expression. NF-κB inhibitor PDTC, PKC inhibitor GF109203X and STAT3 inhibitor Stattic significantly attenuated LMP1-induced Pim1 expression, and while AP-1 inhibitor SR11302 showed no inhibitory effect. Interestingly, Pim1 inhibitor quercetagetin significantly inhibited the proliferation of CNE1-LMP1-OV cells. CONCLUSION: LMP1 mediates Pim1 expression through NF-κB, PKC and STAT3 signaling, which promotes the proliferation of NPC cells and participate in the clinical progression of NPC.

[Temporal and Spatial Distribution of the Soil Water δD and δ18O in a Typical Karst Valley: A Case Study of the Zhongliang Mountain, Chongqing City].

In this study, we analyzed the stable hydrogen and oxygen isotopes of precipitation and three different land use patterns (cultivated land, grass land, and forest land) at 0-15 cm and 15-45 cm in a karst ridge-trough area (Zhongliang Mountain, Beibei District, Chongqing) in May 2017 and September 2017 to investigate the spatial and temporal variation of stable isotopes in different soil profiles using the isotope tracer technique. The results show that:① The average values of the soil water δD and δ18O are -50.0‰±33.6‰ and -7.9‰±4.3‰, respectively, and all plot around the local meteoric water line (LMWL), indicating that precipitation is the main source of the soil water supply in this area. ② The seasonal variations of δD and δ18O of the soil water are significant in different months of the rainy season, May (-19.4‰±6.8‰ and -4.1‰±1.0‰)>September (-82.2 ‰±14.0‰ and -11.9‰±2.2‰). ③ However, there is no significant difference in the soil water δD and δ18O under different land use patterns. ④ The soil water δD and δ18O change with soil depth gradients, which decrease along the depth in vertical direction for all types of soil land use in May but mainly increase/decrease in the cultivated land and woodland/grassland in September, respectively.

Oxyresveratrol prevents lipopolysaccharide/d-galactosamine-induced acute liver injury in mice.

Oxyresveratrol (Oxy) is a natural polyhydroxystilbene abundant in mulberry that has anti-inflammation and anti-oxidant activities. We evaluated the protective effect of Oxy in the context of the lipopolysaccharide and d-galactosamine (LPS/d-GalN) induced acute liver injury. Oxy restricted the development of histopathological changes, markedly reduced the activity of alanine transaminase (ALT) and aspartate transaminase (AST), which are indicators of impaired liver function. Oxy significantly regulated the contents of oxidative stress related enzymes and products, and inhibited expressions of inflammatory mediators and cytokines. Oxy treatment diminished the Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway in liver, activated the Kelch-like ECH-associated protein 1(Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, and increased expressions of heme oxygenase 1 (HO-1) and quinine oxidoreductase 1(NQO1). Pretreatment with Oxy decreased LPS/d-GalN stimulated hepatocyte apoptosis by efficaciously raising the B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X (Bax) ratio, inhibiting the expression and activation of caspases, and activating the phosphoinoside-3-kinase (PI3K)-Akt pathway. Our results demonstrate the hepatoprotective efficacy of Oxy. The protection is mainly due to the prevention of TLR4/NF-κB pathway activation, induced activation of Keap1-Nrf2 signaling pathway, and decreased hepatocyte apoptosis. Oxy warrants further study as a potential therapeutic agent candidate for the management of acute liver injury.