MMP11 and MMP17 are potential biomarkers for uterine corpus endometrial carcinoma prognosis

Background Matrix metalloproteinases (MMP) are important proteases that degrade the extracellular matrix (ECM) and thus essentially mediate tumor vascularization, metastasis, and invasion. However, their potential roles in uterine corpus endometrial carcinoma (UCEC) are not fully understood. Patients and methods The expression, prognostic value, and correlation of UCEC patients with MMP were investigated using data from The Cancer Genome Atlas (TCGA) and other databases. Furthermore, differentially expressed genes (DEGs) were identified and their biological functions and correlations with infiltrating immune cells were analyzed. Results A total of 22 MMPs were found to be abnormally expressed in UCEC tumor tissues, and high expression of MMP11 and MMP17 were associated with a better UCEC prognosis. MMP11 and MMP17 were observed to be significantly enriched in tumor tissue ECM and were associated with pathways involving degradation, glycolytic metabolism, and PI3K-Akt signaling. Infiltration of natural killer (NK), mast, and NK CD56bright cells was enhanced in tumor tissues with high MMP11 and MMP17 expression. Conclusion MMP11 and MMP17 may affect UCEC prognosis by influencing immune cell infiltration and may be potential UCEC biomarkers (AU)

Does Leader-Member Exchange (LMX) Ambivalence Influence Employees' Constructive Deviance?

The ambivalent experience of superior-subordinate relationships is widespread in organisations and has gradually become an important factor influencing employees to actively engage in extra-role behaviours. However, employees' constructive deviance is extremely important for organisational development as they are important extra-role behaviours for organisational innovation and change. Owing that academic research on the antecedents of employees' constructive extra-role behaviours has lacked attention to individual emotional variables such as the leader-member exchange ambivalence, by drawing on self-control resource theory and social cognitive theory, this study examined the effects of leader-member exchange ambivalence on employees' constructive deviance, as well as the role of ego depletion and role-breadth self-efficacy. Based on a two-point questionnaire survey of 332 employees from different industries in China, the study tested hypotheses with SPSS 27 and AMOS 27 and found that the more leader-member exchange ambivalence, the less likely they were to engage in employees' constructive deviance, leader-member exchange ambivalence affected employees' constructive deviance through ego depletion, and when role-breadth self-efficacy is high, the lower the ego depletion of employees with leader-member exchange ambivalence, the more likely they are to engage in employees' constructive deviance. This study is intended to guide organisations to pay attention to the problem of individual internal conflict arising from superior-subordinate relationships, to remove the barriers to constructive transgression by individuals, and to truly exploit the innovative capacity of individual organisations. The study suggests that managers should pay attention to the negative effects of employees' perceived ambivalent experiences of supervisor-subordinate relationships, maintain consistency, and build positive social exchange relationships with their employees. Organisations should strengthen the training of leaders and employees to eliminate the serious internal attrition that organisations face from social network relationships. And employees should face the limitations of resources and reduce dependence on the leader-member exchange relationship as the dependence for their work attitudes and behaviours.

MMP11 and MMP17 are potential biomarkers for uterine corpus endometrial carcinoma prognosis.

BACKGROUND: Matrix metalloproteinases (MMP) are important proteases that degrade the extracellular matrix (ECM) and thus essentially mediate tumor vascularization, metastasis, and invasion. However, their potential roles in uterine corpus endometrial carcinoma (UCEC) are not fully understood. PATIENTS AND METHODS: The expression, prognostic value, and correlation of UCEC patients with MMP were investigated using data from The Cancer Genome Atlas (TCGA) and other databases. Furthermore, differentially expressed genes (DEGs) were identified and their biological functions and correlations with infiltrating immune cells were analyzed. RESULTS: A total of 22 MMPs were found to be abnormally expressed in UCEC tumor tissues, and high expression of MMP11 and MMP17 were associated with a better UCEC prognosis. MMP11 and MMP17 were observed to be significantly enriched in tumor tissue ECM and were associated with pathways involving degradation, glycolytic metabolism, and PI3K-Akt signaling. Infiltration of natural killer (NK), mast, and NK CD56bright cells was enhanced in tumor tissues with high MMP11 and MMP17 expression. CONCLUSION: MMP11 and MMP17 may affect UCEC prognosis by influencing immune cell infiltration and may be potential UCEC biomarkers.

Proteomic analysis of amniotic fluid to identify potential targets predicting preterm delivery.

Preterm delivery is a common complication of pregnancy which leads to significant neonatal mortality and morbidity. Identifying predictive markers linked to spontaneous preterm delivery (SPTD) is important for effective treatment and prevention of PTD. To explore potential biomarkers related to SPTD, we performed proteomics analysis in amniotic fluid (AF). In total, we enrolled 30 pregnant women with singleton gestation who underwent clinically indicated amniocentesis at 15-24 weeks of gestation. LC-MS analysis was used to analyze the AF samples of 10 women with SPTD < 34 weeks after cervix cerclage (Preterm group), 10 women with term delivery (TD) ≥ 34 weeks after cervix cerclage (Term group), and 10 women who delivered at term (Normal group). ELISA validation was performed for candidate proteins in a second independent cohort. As a result, we identified 44 differentially expressed proteins (DEPs, P < 0.05) via proteomic analysis, and based on that, 9 primary pathways were also determined in SPTD. Results of the ELISA assay confirmed that the increased concentration of Serpin A1, decreased concentrations of Renin and IGFBP4 were significantly associated with SPTD at ≤34 weeks.

Optimizing the Practice Environment for Medical Staff in the Post-pandemic Era: A Discrete Choice Experiment.

Objective: This study aimed to elicit the stated job preferences of Chinese medical staff in the post-pandemic era and identify the relative importance of different factors in the practice environment. Methods: We used an online discrete choice experiment (DCE) survey instrument to elicit the job preferences of medical staff (doctors and nurses) in tertiary hospitals in Anhui, China. Attributes and levels were generated using qualitative methods, and four attributes were considered: career development, workload, respect from society, and monthly income. A set of profiles was created using a D-efficient design. The data were analyzed considering potential preference heterogeneity, using the conditional logit model and the latent class logit (LCL) model. Results: A total of 789 valid questionnaires were included in the analysis, with an effective response rate of 73.33%. Career development, workload, respect from society, and monthly income were significant factors that influenced job preferences. Three classes were identified based on the LCL model, and preference heterogeneity among different medical staff was demonstrated. Class 1 (16.17%) and Class 2 (43.51%) valued respect from society most, whereas Class 3 (40.32%) prioritized monthly income. We found that when respect from society was raised to a satisfactory level (50-75% positive reviews), the probability of medical staff choosing a certain job increased by 69.9%. Conclusion: Respect from society was the most preferred attribute, while workload, monthly income, and career development were all key factors in the medical staff's job choices. The heterogeneity of the medical professionals' preferences shows that effective policy interventions should be customized to accommodate these drive preferences.

Xiao-Luo-Wan treats propylthiouracil-induced goiter with hypothyroidism in rats through the PI3K-AKT/RAS pathways based on UPLC/MS and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Goiter with hypothyroidism occurs in several thyroid diseases. Xiao-Luo-Wan (XLW), which contains Scrophularia ningpoensis Hemsl., Fritillaria thunbergii Miq. and Ostrea gigas Thunberg, has been used as an effective Chinese medicine for the treatment of goiters in China for hundreds of years. Based on clinical observations and experimental studies, XLW also exerts a certain effect on hypothyroidism. However, the therapeutic mechanism of XLW remains unclear. AIM OF THE STUDY: The present study aimed to investigate the therapeutic effect of XLW on propylthiouracil (PTU)-induced goiter with hypothyroidism in rats and to uncover the underlying molecular mechanism using ultra high-performance liquid chromatography-mass spectrometry (UPLC/MS), network pharmacology, and molecular docking simulations. MATERIALS AND METHODS: After successful modeling, the remaining rats were randomly divided into a model group, an Euthyrox group, an XLW group, and a control group. The corresponding drugs were given by gavage for four consecutive weeks. The growth status was monitored, the relative thyroid weight was calculated, and the total serum T3, T4, and TSH content were detected. Hematoxylin-eosin (H&E) staining was used to observe the pathological changes in the thyroid glands. The chemical components of the XLW were identified by UPLC/MS and the putative targets of XLW were predicted using multiple databases. We performed network pharmacology based on the intersection of goiter/hypothyroidism-related targets and XLW targets. Then, we performed KEGG pathway enrichment analysis, and key targets were further screened using protein-protein interaction (PPI) networks. Finally, molecular docking was used to predict the binding ability of XLW identified components and the key targets. RESULTS: XLW significantly increased the levels of T3 and T4, and reduced TSH, increased body weight, and decreased swollen thyroid glands in PTU-induced rats. XLW promoted the morphological recovery of thyroid follicles and epithelial cells. Twenty-one main chemical components of XLW were identified using UPLC/MS. 270 potential gene targets of XLW and 717 known targets of goiter/hypothyroidism disease were obtained by searching the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), Swiss Target Prediction, and UniProt databases. A total of 83 KEGG pathways were enriched with phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) and RAS signaling pathways. PPI analysis revealed nine key targets of kinase-protein kinase B (AKT) 1, interleukin (IL) 6, vascular endothelial growth factor A (VEGFA), tumor necrosis factor (TNF), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), epidermal growth factor receptor (EGFR), GTPase HRas (HRAS), matrix metalloproteinase (MMP) 9, and heat shock protein 90 alpha family class A member 1 (HSP90AA1). Molecular docking verified which drug components had good binding ability to key targets (all ≤5 kcal/mol). CONCLUSION: For PTU-induced goiter with hypothyroidism in rats, XLW improves thyroid function, reduces goiter, increases body weight, and promotes the recovery of thyroid follicles and epithelial cells. The underlying molecular mechanism suggests that XLW may regulate thyroid hormone signaling by regulating the PI3K-AKT, RAS, and other signaling pathways. This study provides a pharmacological and biological basis for using XLW to treat goiter with hypothyroidism.

The Aqueous Extract of Gynura divaricata (L.) DC. Improves Glucose and Lipid Metabolism and Ameliorates Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by hyperglycemia and dyslipidemia caused by impaired insulin secretion and resistance of the peripheral tissues. A major pathogenesis of T2DM is obesity-associated insulin resistance. Gynura divaricata (L.) DC. (GD) is a natural plant and has been reported to have numerous health-promoting effects on both animals and humans. In this study, we aimed to elucidate the regulatory mechanism of GD improving glucose and lipid metabolism in an obesity animal model induced by high-fat and high-sugar diet in combination with low dose of streptozocin and an insulin-resistant HepG2 cell model induced by dexamethasone. The study showed that the water extract of GD (GD extract A) could significantly reduce fasting serum glucose, reverse dyslipidemia and pancreatic damage, and regulate the body weight of mice. We also found that GD extract A had low toxicity in vivo and in vitro. Furthermore, GD extract A may increase glucose consumption in insulin-resistant HepG2 cells, markedly inhibit NF-κB activation, and decrease the impairment in signaling molecules of insulin pathway, such as IRS-1, AKT, and GLUT1. Overall, the results indicate that GD extract A is a promising candidate for the prevention and treatment of T2DM.

Increased Heme Oxygenase-1 and Nuclear Factor Erythroid 2-Related Factor-2 in the Placenta Have a Cooperative Action on Preeclampsia.

BACKGROUND: Previous studies have shown that oxidative stress is an important factor in preeclampsia (PE). Heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor-2 (Nrf2) are protective proteins that are involved in combating oxidative stress in the body. Nrf2 is also an essential upstream transcription factor regulating HO-1. This study was aimed at exploring the physiological roles of HO-1 and Nrf2 in PE. METHODS: Serum and placenta were collected from 30 patients who presented with severe PE and 30 healthy pregnant females. HO-1 and Nrf2 levels in placenta were measured. Following stimulation of the HTR-8/SVneo cell line with tert-butylhydroquinone (tBHQ), an Nrf2 activator, nuclear Nrf2 protein and HO-1 mRNA levels were determined. RESULTS: Compared with the healthy pregnancy group, HO-1 protein and mRNA levels were increased in placental samples obtained from the severe PE group (p < 0.01, p < 0.05). Similar increases were also observed for Nrf2 protein levels (p < 0.01). Nuclear Nrf2 protein and HO-1 mRNA levels were both increased in the HTR-8/SVneo cell line following stimulation with tBHQ (p < 0.05). CONCLUSION: Patients with severe PE may be protected against oxidative injury following an elevation in HO-1 and Nrf2 levels. Nrf2 is likely to have a synergistic effect on HO-1 in PE.

Prenatal alcohol exposure and offspring liver dysfunction: a systematic review and meta-analysis.

PURPOSE: Limited studies have reported the effect of prenatal alcohol exposure (PAE) on fetal liver development or liver dysfunction. The current review was conducted to systematically review published studies of PAE and liver dysfunction. METHODS: Pub Med, Embase and Web of Science database were searched using terms of "prenatal alcohol exposure" and "liver" or "fetal alcohol spectrum disease" and "liver". The pooled effect size of alcohol exposure was assessed by Hedges's g and 95 % confidence interval (CI) using fixed model or random model depending on the heterogeneity determined by Q test and I (2) statistic. RESULTS: A total of 23 studies were included. The results indicated that gestation alcohol exposure resulted in significant reduction of fetal body weight (Hedges's g = -6.854 ± 1.149, 95 % CI -9.106 to -4.602, P < 0.001), but not fetal liver weight reduction (Hedges's g = -0.076 ± 0.878, 95 % CI -1.799 to 1.647, P = 0.931). PAE resulted in significant decline in protein synthesis or enzyme activity of offspring fetal liver including glutathione and 25(OH)2D (Hedges's g = -1.149 ± 0.108, 95 % CI -1.361 to -0.938, P < 0.001), as well as significant increase in proteins including oxidants and collagen (Hedges's g = 1.330 ± 0.146, 95 % CI 1.044-1.616, P < 0.001). CONCLUSION: These results suggested that PAE affects fetal body weight but not liver weight, and that PAE may result in offspring fetal liver dysfunction.

Upregulation of microRNA-132 in gastric cancer promotes cell proliferation via retinoblastoma 1 targeting.

Gastric cancer is one of the most frequent malignancies and a leading cause of cancer-related mortality worldwide. MicroRNAs (miRs), a class of small non­coding RNAs, have been shown to be critical in tumorigenesis. In the present study, the expression levels of miR­132 were analyzed in gastric cancer samples using quantitative reverse transcription­polymerase chain reaction. In addition, the cell viability, proliferation and invasion abilities were determined in two gastric cancer cell lines, NCI­N87 and MGC80­3, that were transfected with miR­132 mimics or antisense oligos. It was found that miR­132 expression was significantly upregulated in gastric cancer tissues when compared with adjacent non­cancerous tissues. At the molecular level, the data demonstrated that miR­132 inhibits the protein levels of retinoblastoma 1 (RB1) by targeting the 3'­untranslated region. Furthermore, reintroduction of RB1 markedly attenuated the proliferative roles of miR­132 overexpression. Therefore, the present results indicate that the miR­132/RB1 regulatory axis may be a potential novel diagnostic and therapeutic target for the treatment of gastric cancer.

Post-traumatic stress disorder status in a rescue group after the Wenchuan earthquake relief.

Previous studies have suggested that the incidence of post-traumatic stress disorder in earthquake rescue workers is relatively high. Risk factors for this disorder include demographic characteristics, earthquake-related high-risk factors, risk factors in the rescue process, personality, social support and coping style. This study examined the current status of a unit of 1 040 rescue workers who participated in earthquake relief for the Wenchuan earthquake that occurred on May 12(th), 2008. Post-traumatic stress disorder was diagnosed primarily using the Clinician-Administered Post-traumatic Stress Disorder Scale during structured interviews. Univariate and multivariate statistical analyses were used to examine major risk factors that contributed to the incidence of post-traumatic stress disorder. Results revealed that the incidence of this disorder in the rescue group was 5.96%. The impact factors in univariate analysis included death of family members, contact with corpses or witnessing of the deceased or seriously injured, near-death experience, severe injury or mental trauma in the rescue process and working at the epicenter of the earthquake. Correlation analysis suggested that post-traumatic stress disorder was positively correlated with psychotic and neurotic personalities, negative coping and low social support. Impact factors in multivariate logistic regression analysis included near-death experience, severe injury or mental trauma, working in the epicenter of the rescue, neurotic personality, negative coping and low social support, among which low social support had the largest odds ratio of 20.42. Findings showed that the occurrence of post-traumatic stress disorder was the result of the interaction of multiple factors.

[Influence of electroacupuncture on hepatic cytochrome P450 1 A 1 expression and lipid peroxidation in nonalcoholic fatty liver rats].

OBJECTIVE: To study the effect of electroacupuncture (EA) on liver cytochrome P450 1 A 1 immunoactivity, superoxide dismutase (SOD) and malondialdehyde (MDA) contents in nonalcoholic fatty liver disease (NAFLD) rats. METHODS: Thirty male SD rats were randomized into normal control (n = 10), model (n = 10) and EA (n = 10) groups. NAFLD model was established by feeding the animal with high-fat forage for 8 weeks. EA (1.6-2 Hz, 1-4 mA) was applied to bilateral "Zusanli" (ST 36), "Fenglong" (ST 40), "Sanyinjiao" (SP 6) and "Taichong" (LR 3) for 15 min, once daily for 4 weeks. Then the rats anesthetized with ether were killed for collecting liver tissue. Following homogenate and centrifugalization of the partial liver tissue, the supernatant was collected for assaying superoxide dismutase (SOD) and malondialdehyde (MDA) contents by xanthinoxidase chromometry and thio-malonylurea chromometry respectively. The other partial liver tissue samples were fixed in 10% formalin, followed by paraffin imbedding and sectioning (4 microm), and staining with streptavidin-perosidase methods respectively for displaying hepatic pathological changes and cytochrom P450 1 A 1 immunoreaction. RESULTS: Compared with control group, hepatic SOD content of model group was significantly lower (P < 0.05), and MDA level and cytochrome P450 1 A 1 (CYP 1 A 1) integrated optic density (IOD) value were obviously higher in model group (P < 0.05). In comparison with model group, liver SOD level of EA group increased considerably (P < 0.05), while MDA level and CYP 1 A 1 IOD of EA group decreased evidently in EA group (P < 0.05). CONCLUSION: EA can effectively reduce lipid peroxidation and up-regulate CYP 1 A 1 expression in nonalcoholic fatty liver tissue, which may contribute to its effect in improving fatty liver.

[Influence of electroacupuncture of "Baihui" (GV 20) and "Sanyinjiao" (SP 6) on hippocampal 5-HT and AChE immuno-activity in chronic depression rats].

OBJECTIVE: To investigate the influence of electroacupuncture (EA) on 5-serotonin (5-HT) and acetyl cholinesterase (AChE) activities in hippocampus tissue in chronic stressed-induced depression rats. METHODS: Thirty-two Wistar rats were randomized into normal control group (n=10), model group (n=11) and EA group (n=11). Chronic depression model was established by lonely raising, and chronic unpredictable mild stress for 21 days. EA (2 Hz, 1 mA) was applied to "Baihui" (GV 20) and "Sanyinjiao" (SP 6) for 20 minutes, once daily for 14 days. 5-HT and AChE expression of hippocampal CA 4 region was detected by using immunohistochemistry, and their integrated optical density (IOD) values were determined by using image analysis system. RESULTS: Compared with normal control group, IOD values of 5-HT and AChE immuno-reaction (IR) positive neurons in hippocampal CA 4 region of model group decreased significantly (P<0.05). In comparison with model group, the IOD values of 5-HT and AChE IR positive neurons of CA 4 region in EA group increased significantly (P<0.05). No significant differences were found between EA and normal control groups in IOD values of both 5-HT and AChE IR positive neurons. CONCLUSION: EA can upregulate 5-HT and AChE expression in hippocampal CA 4 region in depression rats, which may contribute to its effect in relieving depression.

[Effect of electroacupuncture of "Hegu" (LI 4)-"Taichong" (LR 3) on colonic nitric oxide synthase and glutathione peroxidase activity and nitric oxide content in depression rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the activity of inducible nitric oxide synthase (iNOS), glutathione peroxidase (GSH-Px) and the content of nitric oxide (NO) in colon tissue of depression rats, so as to reveal its mechanism in protecting colonic tissue under depression. METHODS: Forty male SD rats were equally randomized into normal, model, medication and EA groups. Depression model was established by using chronic unpredictable mild stress stimulation (forced ice-water swimming, electric shock, tail-clamping, etc) combined with lonely raising for 21 days. At the same time of modeling, Fluoxetine (1.8 mg/kg, intragastric perfusion) was given to the rats of medication group, once daily for 21 days. EA (1.5-2 Hz, 1-3 mA) was applied to bilateral "Hegu" (LI 4) and "Taichong" (LR 3) for 20 min, once daily for 21 days. The activity of iNOS, GSH-Px and the content of NO in colon tissue were detected by ultraviolet spectrophotometer method. RESULTS: In comparison with normal control group, iNOS activity and NO content in colon tissue increased significantly (P<0.05), and GSH-Px activity decreased considerably (P<0.05) in model group. Whereas compared with model group, iNOS activity and NO content decreased significantly (P<0.05), and GSH-Px activity increased significantly in EA and medication groups. No significant differences were found between EA group and medication group in these 3 indexes (P>0.05). CONCLUSION: EA of "Hegu" (LI 4) and "Taichong" (LR 3) can reduce stress induced increase of both iNOS activity and NO content, and decrease of GSH-Px activity in colon tissue in depression rats, which may contribute to its effect in protecting the digestive tract from injury under depression.