Investigation of the Mechanisms and Experimental Verification of Yulin Formula in the Treatment of Diminished Ovarian Reserve via Network Pharmacology.

Purpose: The aim of this study is to examine, using network pharmacology analysis and experimental validation, the pharmacological processes by which Yulin Formula (YLF) reduces cyclophosphamide-induced diminished ovarian reserve (DOR). Methods: First, information about the active components, associated targets, and related genes of YLF and DOR was gathered from open-access databases. The primary targets and pathways of YLF to reduce DOR were predicted using studies of functional enrichment from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Protein-Protein Interaction (PPI) networks. Second, we built a cyclophosphamide-induced diminished ovarian reserve (DOR) rat model to verify the primary target proteins implicated in the predicted signaling pathway to explore the mechanism of improve ovarian function of YLF. Results: 98 targets met the targets of the 82 active ingredients in YLF and DOR after searching the intersection of the active ingredient targets and DOR targets. Fourteen targets, including AKT and Caspase-3 among others, were hub targets, according to the PPI network study. The PI3K/AKT pathway was revealed to be enriched by numerous targets by the GO and KEGG enrichment studies, and it was used as a target for in vivo validation. Animal studies showed that YLF administration not only reduced the number of atretic follicles, the proportion of TUNEL-positive ovarian cells, the rate of apoptosis of granulosa cells (GCs) and the proportion of abnormal mitochondria in DOR rats, but also reversed the high expression of Caspase-3, Caspase-9, BAX, cytochrome C, PI3K and P-AKT, improving the ovarian reserve in cyclophosphamide (CTX)-induced DOR rats. Conclusion: Our research results predicted the active ingredients and potential targets of YLF-interfering DOR by an integrated network pharmacology approach, and experimentally validated some key target proteins participated in the predicted signaling pathway. A more comprehensive understanding of the pharmacological mechanism of YLF for DOR treatment was obtained.

Abusive supervision, thwarted belongingness, and workplace safety: A group engagement perspective.

Drawing from the group engagement model of justice, we examine how and when higher abusive supervision relates to fewer safety behaviors and worse safety performance. In Study 1, a 2-wave survey study of 468 manufacturing technicians, we found that belongingness need satisfaction mediated the negative relationship between abusive supervision and safety behavior. In Study 2, a multiwave survey study of 589 airline pilots, we found that safety behavior mediated the adverse relationship between abusive supervision and downstream objective safety performance. Higher trait social standing uncertainty was associated with a stronger adverse relationship between abusive supervision and safety. Indirect relationships of abusive supervision with safety behavior (Study 1) and safety performance (Study 2) were stronger among individuals with higher social standing uncertainty. We discuss the theoretical implications of these findings for managing abusive supervision and safety at work. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Aggression-preventive supervisor behavior: Implications for workplace climate and employee outcomes.

Workplace aggression remains a serious and costly issue for organizations; thus, it is imperative to understand ways to reduce workplace aggression. To address this need, we used 2 independent samples with varied study designs, one at the employee level and the other at both employee and unit levels, to examine the role of aggression-preventive supervisor behavior (APSB) in aggression-prevention processes. In Sample 1 (237 nurses), we used structural equation modeling to examine the role of individual observations of APSB. First, we found that individual employees' observations of APSB positively related to their individual violence-prevention climate (VPC) perceptions. Further, VPC perceptions mediated the relations between APSB and employees' exposure to coworker aggression, job attitudes, and physical symptoms. In Sample 2 (337 nurses), we used multilevel regression analysis to examine the positive role of APSB in managing the aggression process. First, we established further support for many of the findings in Sample 1. In addition, we found that shared unit-level VPC mediated the relations of unit-level APSB with employees' exposure to aggression from coworkers, their physical symptoms, and turnover intention. Finally, evidence from Sample 2 supported favorable, direct relations of individual- or unit-level APSB with employees' aggression-prevention compliance and turnover intention. Implications for studying context-specific leadership behavior and designing aggression-prevention interventions are discussed. (PsycINFO Database Record

Chinese Employees' Psychological Responses to Abusive Supervisors: The Roles of Gender and Self-Esteem.

Drawing on the conservation of resources theory, the relations between abusive supervision and emotional exhaustion and intent to leave were examined, as well as the gender differences in these relations. Moreover, the moderating effect of self-esteem was tested in an integrated model stipulating that the gender-moderating effect was mediated by the abusive supervision × self-esteem interaction. Data were collected from 264 employees (111 men; M age = 32.0 years; M tenure = 9.2 years). Results of regression analyses indicated that abusive supervision was positively correlated to emotional exhaustion and intent to leave. Women reported higher emotional exhaustion and intent to leave than men. The relations of interest were stronger among employees with higher self-esteem (emotional exhaustion: ß = 0.44; intent to leave: ß = 0.53). The interaction of abusive supervision × self-esteem mediated the gender-moderating effect. Women's stronger responses to abusive supervision may be related to their higher self-esteem, possibly because of the importance of employment to Chinese women.

To branch out or stay focused? Affective shifts differentially predict organizational citizenship behavior and task performance.

We draw from personality systems interaction (PSI) theory (Kuhl, 2000) and regulatory focus theory (Higgins, 1997) to examine how dynamic positive and negative affective processes interact to predict both task and contextual performance. Using a twice-daily diary design over the course of a 3-week period, results from multilevel regression analysis revealed that distinct patterns of change in positive and negative affect optimally predicted contextual and task performance among a sample of 71 employees at a medium-sized technology company. Specifically, within persons, increases (upshifts) in positive affect over the course of a workday better predicted the subsequent day's organizational citizenship behavior (OCB) when such increases were coupled with decreases (downshifts) in negative affect. The optimal pattern of change in positive and negative affect differed, however, in predicting task performance. That is, upshifts in positive affect over the course of the workday better predicted the subsequent day's task performance when such upshifts were accompanied by upshifts in negative affect. The contribution of our findings to PSI theory and the broader affective and motivation regulation literatures, along with practical implications, are discussed. (PsycINFO Database Record

The crossover of psychological distress from leaders to subordinates in teams: The role of abusive supervision, psychological capital, and team performance.

This study examines the underlying mechanism of the crossover process in work teams. Drawing on conservation of resources theory, we hypothesize that a leader's psychological distress positively influences subordinates' psychological distress through abusive supervision. We further hypothesize that team performance attenuates the association between a leader's psychological distress and abusive supervision. In addition, we expect that psychological capital attenuates the positive relationship between abusive supervision and subordinates' psychological distress. Participants were drawn from 86 business teams, and multisource data were collected. The hypotheses were tested with multilevel analysis. Results supported the crossover of psychological distress from leader to subordinates, and abusive supervision serves as a mediating mechanism. The positive relationship between a leader's distress and abusive supervision is stronger when team performance is lower. In addition, the positive relationship between abusive supervision and subordinates' psychological distress is stronger when subordinates' psychological capital is lower.

Be Mindful of What You Impose on Your Colleagues: Implications of Social Burden for Burdenees' Well-being, Attitudes and Counterproductive Work Behaviour.

This paper describes two studies of a new relational variable social burden and its implications for employees' well-being, job attitudes and counterproductive work behaviours. Social burden is defined as behaviours from colleagues that elicit the focal employees' social support. Across two separate samples (540 nurses and 172 university employees), we found that social burden differentiated from psychological aggression and incivility, respectively. A separate cross-sectional sample of 273 nurses from Study 1 revealed that social burden from colleagues was positively associated with focal employees' anxiety, irritation, depressive mood, physical symptoms, job dissatisfaction and turnover intentions. Study 2 used a time-lagged design with a separate sample of 383 university employees and 160 of their coworkers. In this study, social burden from supervisors and from coworkers were together predictive of employees' subsequent emotional strains and job attitudes, as measured 6 months later. With respect to sources of social burden, social burden from supervisors more strongly predicted job attitudes and counterproductive work behaviours directed at others, and social burden from coworkers more strongly predicted emotional strains.

Activin A expression in esophageal carcinoma and its association with tumor aggressiveness and differentiation.

The aim of the present study was to investigate the expression of activin A in esophageal carcinoma and its association with tumor differentiation and metastasis. A total of 57 esophageal carcinoma patients and 36 controls were included in the current study. The mRNA and protein expression levels of activin A in esophageal tumors or normal esophageal tissues were determined by reverse transcription-quantitative polymerase chain reaction and immunohistochemical analysis. In addition, the association of activin A expression with esophageal carcinoma differentiation, metastasis and recurrence postoperatively was analyzed. The mRNA and protein expression levels of activin A in esophageal carcinoma were significantly higher compared with those in normal esophageal tissues (P<0.05). The expression of activin A was higher in poorly-/moderately-differentiated esophageal tumor tissues compared with that of well-differentiated or control tissues (P<0.05). Furthermore, the expression of activin A in poorly-differentiated esophageal tumor tissues was higher compared with that of moderately-differentiated tissues (P<0.05). A positive correlation was also observed between differentiation degree and activin A expression. The expression of activin A was higher in patients with lymph node metastasis compared with those without metastasis (P<0.05). The cumulative survival rate of patients with a high expression of activin A at 1, 2 and 3 years postoperatively was significantly decreased compared with that of patients with a lower expression of activin A (P<0.05); by contrast, the cumulative recurrence rate was significantly higher in patients with a lower activin A expression (P<0.05). In conclusion, abnormal expression of activin A was detected in esophageal tumor tissues, which was correlated with the tumor differentiation, metastasis, survival and recurrence. In conclusion, activin A may be used as an auxiliary index in the diagnosis and prognosis of clinical esophageal carcinoma.

Political skill: A proactive inhibitor of workplace aggression exposure and an active buffer of the aggression-strain relationship.

In the current study we examined the role of 4 dimensions of political skill (social astuteness, interpersonal influence, networking ability, and apparent sincerity) in predicting subsequent workplace aggression exposure based on the proactive coping framework. Further, we investigated their buffering effects on the negative outcomes of experienced workplace aggression based on the transactional stress model. Data were collected from nurses at 3 time points: before graduation (Time 1, n = 346), approximately 6 months after graduation (Time 2, n = 214), and approximately 12 months after graduation (Time 3, n = 161). Results showed that Time 1 interpersonal influence and apparent sincerity predicted subsequent physical aggression exposure. Exposure to physical and/or psychological workplace aggression was related to increased anger and musculoskeletal injury, and decreased job satisfaction and career commitment. Further, all dimensions of political skill but networking ability buffered some negative effects of physical aggression, and all dimensions but social astuteness buffered some negative effects of psychological aggression.

Workplace mistreatment climate and potential employee and organizational outcomes: a meta-analytic review from the target's perspective.

This meta-analytic study summarizes relations between workplace mistreatment climate-MC (specific to incivility, aggression, and bullying) and potential outcomes. We define MC as individual or shared perceptions of organizational policies, procedures, and practices that deter interpersonal mistreatment. We located 35 studies reporting results with individual perceptions of MC (psychological MC) that yielded 36 independent samples comprising 91,950 employees. Through our meta-analyses, we found significant mean correlations between psychological MC and employee and organizational outcomes including mistreatment reduction effort (motivation and performance), mistreatment exposure, strains, and job attitudes. Moderator analyses revealed that the psychological MC-outcome relations were generally stronger for perceived civility climate than for perceived aggression-inhibition climate, and content contamination of existing climate scales accentuated the magnitude of the relations between psychological MC and some outcomes (mistreatment exposure and employee strains). Further, the magnitudes of the psychological MC-outcome relations were generally comparable across studies using dominant (i.e., most commonly used) and other climate scales, but for some focal relations, magnitudes varied with respect to cross-sectional versus prospective designs. The 4 studies that assessed MC at the unit-level had results largely consistent with those at the employee level.

Physiological mechanisms that underlie the effects of interactional unfairness on deviant behavior: the role of cortisol activity.

Although experiencing unfairness is a primary source of stress, there are surprisingly few studies that have examined the physiological underpinnings of unfairness. Drawing from social self-preservation theory, we derive predictions regarding the effects of interactional unfairness on activity in the hypothalamic-pituitary-adrenocortical (HPA) axis, which is one of the body's primary hormonal systems for responding to stress. Using an experimental design with objective physiological measures, we found support for our hypothesis that interactional unfairness triggers the release of cortisol by the HPA axis. This cortisol activity in turn mediated the effects of interactional unfairness on deviant behavior. This indirect effect remained significant after controlling for established attitudinal and self-construal mediators of the justice-deviance relationship. We discuss the theoretical and practical implications of these findings for the occupational stress and organizational justice literatures.

Sodium nitroprusside (SNP) sensitizes human gastric cancer cells to TRAIL-induced apoptosis.

AIM: To investigate the effects of the nitrous oxide (NO)-donor sodium nitroprusside (SNP) on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in human gastric cancer cells. METHODS: The MTT assay and flow cytometry were used to detect cellular proliferation and markers of apoptosis, respectively. Expression levels of caspases-8, and 9 were determined by Western blot. Changes in Nitric Oxide Synthase (NOS) activity, NO production, and caspase activation were also evaluated. RESULTS: We found that TRAIL induced apoptosis and cell cycle arrest in human gastric cancer cell lines, and that this effect was mediated by NO production, and activation of both the extrinsic and intrinsic signaling pathways of apoptosis. In addition, we found that the NO-donor SNP sensitizes gastric cancer cells to TRAIL-mediated apoptosis. Treatment of cells with both TRAIL and SNP resulted in increased activation of caspase-8 and caspase-9 and NO release. Inhibition of caspase-8 blocked cell TRAIL-induced apoptosis, while a selective caspase-9 inhibitor was unable to prevent apoptosis induced by either TRAIL or TRAIL plus SNP. Inhibition of NOS could block the activation of caspase-9, but had no obvious effect on cell apoptosis. CONCLUSIONS: SNP-sensitized gastric cancer cells to TRAIL-induced cytotoxicity by stimulating the release of NO, in turn facilitating the mitochondria-mediated signal transduction pathway. The engagement of the mitochondria signaling pathways along with the TRAIL death receptor signaling pathway synergistically increase levels of apoptosis in these cells.

Celecoxib inhibits Helicobacter pylori-induced invasion of gastric cancer cells through an adenine nucleotide translocator-dependent mechanism.

Cyclooxygenase-2 (COX-2) inhibitor, celecoxib, causes growth inhibition of human gastric carcinoma cells, but it remains unclear whether celecoxib inhibits Helicobacter pylori-induced invasion of gastric cancer cells. The adenine nucleotide translocator (ANT) is a mitochondrial bi-functional protein. We speculate that ANT-dependent pathways might contribute to H. pylori-induced invasion and metastasis of gastric cancer cells. Therefore, in the present study, we evaluate the effect of celecoxib on H. pylori-induced gastric cancer cell motility and invasion. We also explore the role of ANTs in H. pylori-induced gastric cancer cell motility and invasion of gastric cancer cell line AGS. Our results demonstrate that celecoxib induces anoikis-like apoptosis and suppresses the proliferation and invasion of gastric cancer cells induced by H. pylori in culture. RT-PCR and Western blot analysis indicates that celecoxib upregulates the expression of ANT1 and ANT3; however, celecoxib did not increase the expression of ANT2. Our results suggest that celecoxib could be an effective means for suppressing proliferation and invasion of gastric cancer cells induced by H. pylori through an adenine nucleotide translocator-dependent mechanism.

Examining the mediating effect of supervisor conflict on procedural injustice-job strain relations: the function of power distance.

The present study examined the associations among procedural injustice, conflict with a supervisor (supervisor conflict), and job strains for employees with different power distance orientations. Using data from 301 university employees, along with corroborative reports from a coworker of each employee, we tested a moderated mediation model in which the indirect effect of procedural injustice on job strains (e.g., anxiety and depression) through supervisor conflict was conditional upon employees' power distance orientation. We found perceived procedural injustice was positively related to supervisor conflict, and this relation was moderated by employees' power distance orientation (as supported by both self- and coworker-reported conflict data). The pattern of the moderating effect indicated the positive relation between procedural injustice and supervisor conflict was only significant among employees with low to moderate power distance orientations. As expected, supervisor conflict served as the underlying mechanism linking perceived procedural injustice and employees' anxiety/depression (as supported by self-reported conflict data). The mediating effect of supervisor conflict was significant for employees with low to moderate power distance orientations but not for employees with high power distance orientation. This study broadens the focus of research on supervisor conflict and presents a more complex model of how perceived injustice influences employees' job strains than is currently available in the literature.

Psychosocial precursors and physical consequences of workplace violence towards nurses: a longitudinal examination with naturally occurring groups in hospital settings.

BACKGROUND: Workplace violence towards nurses is prevalent and consequential, contributing to nurses' reduced health and safety, worsened job attitudes, and compromised productivity. OBJECTIVES: To examine if organizational violence prevention climate as perceived by nurses predicts nurses' physical violence exposure and if physical violence exposure predicts nurses' somatic symptoms and musculoskeletal disorder symptoms. DESIGN: A two-wave longitudinal design with naturally occurring groups, with a 6-month interval. METHODS: Analysis of covariance and logistic regression were applied to test the proposed hypotheses among 176 nurses from two hospitals in the U.S. who participated in both surveys required by this study. All nurses from the two hospitals were recruited to participate voluntarily. The response rate was 30% for the first survey and 36% for the follow-up survey. Among the subjects, only 8 were male. On average, the subjects were about 45 years old, had a job tenure of about 17 years, and worked approximately 37 h per week. RESULTS: Violence prevention climate, specifically the dimension of perceived pressure against violence prevention, predicted nurses' chance of being exposed to physical violence over six months (odds ratio 1.69), with no evidence found that violence exposure affected change in climate reports. In addition, results supported that nurses' physical violence exposure had effects on somatic symptoms, and upper body, lower extremity, and low back pain over six months. CONCLUSIONS: Findings of this study suggest that reducing organizational pressure against violence prevention will help decrease the chance of nurses' physical violence exposure and benefit their health and safety.

Ad-KDRscFv:sTRAIL displays a synergistic antitumor effect without obvious cytotoxicity to normal tissues.

AIM: To investigate the antitumor activities and safety of Ad-KDRscFv, Ad-sTRAIL (114-281) and Ad-KDRscFv:sTRAIL in vivo and in vitro. METHODS: Recombinant replication-defective adenovirus vectors encoding either the extracellular domain (114-281 aa) of TRAIL, the KDRscFv (single chain antibody (scFv) against human vascular endothelial growth factor (VEGF) receptor KDR) or the fusion gene of KDRscFv:sTRAIL were constructed and transfected into HEK 293 cells for virus packaging. The recombinant virus particles were then infected human tumor cell lines of liver cancer (HepG2), gastric cancer (SGC-7901), colorectal cancer (SW480) and normal human liver cell line (LO2) to investigate the antitumor activities. Nude mice of the subcutaneous tumor models were established with HepG2 cells and were randomly divided into different groups to investigate the therapeutic effect and safety of these adenovirus particles on hepatocellular carcinoma. The expression of foreign proteins and the effect on microvascular number were also evaluated. RESULTS: All three adenovirus particles could induce apoptosis of cancer cells lines HepG2, SGC-7901 and SW480, but had no obvious lethal effect on LO2 cells. Ad-KDRscFv:sTRAIL showed the strongest tumoricidal effect. After intratumoral injection with these adenovirus particles on nude mice model, all the three adenoviruses could inhibit the tumor growth and angiogenesis, and the expression of foreign proteins (sTRAIL, KDRscFv and KDRscFv:sTRAIL fusion protein) was restricted to liver and tumor tissues. In coincidence with the result in vitro, Ad-KDRscFv:sTRAIL also had the strongest antitumor activity in vivo. No obvious pathological changes were detected in vivo. CONCLUSIONS: Replication-defective recombinant adenovirus of Ad-KDRscFv, Ad-sTRAIL and Ad-KDRscFv:sTRAIL all had tumoricidal activities and Ad-KDRscFv:sTRAIL showed the strongest effect. All three adenoviruses had no obvious toxicity to normal cells and tissues in vitro and in vivo.

Silencing of the hPOT1 gene by RNA inference promotes apoptosis and inhibits proliferation and aggressive phenotype of gastric cancer cells, likely through up-regulating PinX1 expression.

BACKGROUND: The human protection of telomeres 1 (hPOT1) protein, a single-strand telomeric DNA binding protein, plays an important role in telomere protection and telomere length regulation. However, its effect on invasion of gastric cancer remains unclear. AIMS: To explore the role of hPOT1 in the proliferation and invasion of gastric cancer cells. METHODS: The gastric expression of hPOT1 was examined in normal gastric mucosa (n=25), intestinal metaplasia (n=20), gastric dysplasia (n=20) and gastric cancer (n=150) by immunohistochemistry. The mean optical density (MOD) of the immunostaining was determined by semi-quantitative image analysis. The role of hPOT1 in the cell proliferation, apoptosis and invasion of gastric cancer 7901 cells was determined by means of the RNA interference (RNAi) of hPOT1 mRNA. The effects of hPOT1 RNAi on the expression of hPinX1 and hTERT were detected with western blotting. RESULTS: The hPOT1 MOD was progressively increased from the normal mucosa to intestinal metaplasia, dysplasia, and gastric cancer. An increased hPOT1 expression significantly correlated with tumour serosal invasion, node metastasis and advanced stage. Transfection of hPOT1 siRNA into SGC-7901 cells led to a decrease in cell proliferation, colony formation and invasion, and also an increase of apoptosis. An up-regulation of hPinX1 and down-regulation of hTERT were found in gastric cancer cells with hPOT1 siRNA. CONCLUSIONS: Increased hPOT1 expression is associated with an advanced tumour stage. hPOT1 RNAi inhibits proliferation and invasion, and induces apoptosis of gastric cancer cells. The effects of hPOT1 RNAi seem to be functionally linked to up-regulation of PinX1 and down-regulation of hTERT.

Silencing of the HCCR2 gene induces apoptosis and suppresses the aggressive phenotype of hepatocellular carcinoma cells in culture.

BACKGROUND: The human cervical cancer oncogene HCCR-2 is overexpressed in various malignant tumors and cell lines, and might function as a negative regulator of the p53 tumor suppressor. Here, we used RNA interference strategies to evaluate the role of HCCR-2 in liver cancer, and to explore its potential therapeutic effect. METHODS: Changes of HepG2 cells stably transfected by an HCCR-2 RNA interference vector were detected by real-time PCR, MTT staining, plate colony formation, flow cytometry, and cell migration experiments. Apoptosis-related protein Bcl-2 and Bax levels were measured by Western blot. RESULTS: Our results showed that of the three siRNA-expressing vectors, siRNA-H3 had a suppressive effect on the expression of HCCR-2 mRNA, interfering with proliferation and migration of HCCR-2. Moreover, the apoptotic rate also increased, and cells transfected by siRNA-H3 were blocked in the G0/G1 stage. Plate colony formation experiments demonstrated that the single cell clone formation capacity of HepG2-H3 cells was clearly lower than that of HepG2 and HepG2-N cells. Western blot results indicated that the expression of Bcl-2 was inhibited, and the expression of Bax was increased. CONCLUSIONS: In summary, RNAi targeting HCCR-2 could be an effective means for suppressing malignant features of hepatocellular carcinoma cells.

RNA interference-mediated hTERT inhibition enhances TRAIL-induced apoptosis in resistant hepatocellular carcinoma cells.

TRAIL has been reported to induce apoptosis in a variety of tumor cell types including hepato-cellular carcinoma (HCC) cell lines. However, considerable numbers of HCC cells, especially some highly malignant tumors, show resistance to TRAIL-induced apoptosis. The molecular mechanisms that regulate sensitivity versus resistance of tumor cells to TRAIL-induced apoptosis remain poorly defined. It has been shown that human telomerase catalytic subunit (hTERT) is overexpressed in human HCCs. In this study, we investigated the effects and the mechanisms of hTERT RNAi on the TRAIL-induced apoptosis of HCC cells that exhibit resistance to TRAIL. Our results indicate that hTERT RNAi sensitizes TRAIL-resistant HCC cells to TRAIL-induced apoptosis. hTERT RNAi-mediated sensitization to TRAIL-induced apoptosis is accompanied up-regulation of procaspases-8 and -9, inhibition of telomerase activity and loss of telomere length. Our results suggest that hTERT RNAi overcame the resistance of the HCC cells against TRAIL, at least in part, via the mitochondrial type II apoptosis pathway and telomerase-dependent pathway.