Analysis of factors associated with IUI pregnancy outcomes in elderly and young patients.

OBJECTIVE: The objective of this study was to investigate the correlation between various factors and the clinical outcomes of Intrauterine Insemination (IUI) in both young and aged patients, aiming to provide a theoretical basis for clinical consultations. METHODS: This retrospective analysis examined a total of 4,221 IUI cycles conducted at the Reproductive Center of Changzhou Maternal and Child Health Hospital between January 2016 and December 2020. The patients were categorized into two groups based on age: the elder group (≥ 35 years) and the young group (< 35 years). RESULTS: The findings of this study revealed a significant association between woman's age and BMI with pregnancy outcomes (0.93, 95% CI: 0.89-0.97) (1.04, 95% CI: 1.01-1.06). Moreover, in young women, both age and Body Mass Index (BMI)were found to be related to pregnancy outcomes (0.97, 95% CI: 0.89-0.97) (1.08, 95% CI: 1.01-1.06). Additionally, BMI and the number of cycles in aged IUI patients were found to be associated with pregnancy outcomes. The pregnancy rate in the second cycle was approximately 1.9 times higher than that in the first cycle (1.9, 95% CI: 0.97-3.77), and in the third cycle, it was approximately 3 times higher than that in the first cycle (3.04, 95% CI: 1.43-6.42). CONCLUSIONS: In conclusion, there is an association between woman's age and BMI and the clinical outcomes of IUI. However, the number of cycles did not affect the pregnancy outcomes in young women. Conversely, in elder women, the number of cycles was found to be related to the IUI pregnancy outcomes, with significantly higher pregnancy rates observed in the second and third cycles compared to the first cycle.

Serum metabolomics reveals the effects of accompanying treatment on fatigue in patients with multiple myeloma.

PURPOSE: The renewal and iteration of chemotherapy drugs have resulted in more frequent long-term remissions for patients with multiple myeloma (MM). MM has transformed into a chronic illness for many patients, but the cancer-related fatigue (CRF) of many MM convalescent patients experience is frequently overlooked. We investigated whether the accompanying treatment of family members would affect MM patients' CRF and explore their serum metabolomics, so as to provide clinicians with new ideas for identifying and treating CRF of MM patients. METHODS: This was a single-center study, and a total of 30 MM patients were included in the study. Patients were divided into two groups based on whether they have close family members accompanying them through the whole hospitalization treatment. These patients received regular chemotherapy by hematology specialists, and long-term follow-up was done by general practitioners. Patients' CRF assessment for several factors used the Chinese version of the Brief Fatigue Inventory (BFI-C). Face-to-face questionnaires were administered at a time jointly determined by the patient and the investigator. All questionnaires were conducted by a general practitioner. The LC-MS-based metabolomics analysis determined whether the patients' serum metabolites were related to their fatigue severity. A correlation analysis investigated the relationship between serum metabolites and clinical laboratory indicators. RESULTS: The fatigue severity of MM patients whose family members participated in the treatment process (group A) was significantly lower than patients whose family members did not participate in the treatment process (group B). There was a statistically significant difference (fatigue severity composite score: t = - 2.729, p = 0.011; fatigue interference composite score: t = - 3.595, p = 0.001). There were no differences between the two groups of patients' gender, age, regarding clinical staging, tumor burden, blood routine, biochemical, or coagulation indexes. There were 11 metabolites, including guanidine acetic acid (GAA), 1-(Methylthio)-1-hexanethiol, isoeucyl-asparagine, L-agaritine, tryptophyl-tyrosine, and betaine, which significantly distinguished the two groups of MM patients. GAA had the strongest correlation with patient fatigue, and the difference was statistically significant (fatigue severity composite score: r = 0.505, p = 0.0044; fatigue interference composite score: r = 0.576, p = 0.0009). The results showed that GAA negatively correlated with albumin (r = - 0.4151, p = 0.0226) and GGT (r = - 0.3766, p = 0.0402). Meanwhile, GAA positively correlated with PT (r = 0.385, p = 0.0473), and the difference was statistically significant. CONCLUSION: The study is the first to report that family presence throughout the whole hospitalization may alleviate CRF in MM patients. Moreover, the study evaluated serum metabolites linked to CRF in MM patients and found that CRF has a significant positive correlation with GAA. GAA may be a more sensitive biomarker than liver enzymes, PT, and serum albumin in predicting patient fatigue. While our sample may not represent all MM patients, it proposes a new entry point to help clinicians better identify and treat CRF in MM patients.

Cellular Metabolomics Reveal the Mechanism Underlying the Anti-Atherosclerotic Effects of Aspirin Eugenol Ester on Vascular Endothelial Dysfunction.

Aspirin eugenol ester (AEE) possesses anti-thrombotic, anti-atherosclerotic and anti-oxidative effects. The study aims to clarify the mechanism underlying the anti-atherosclerotic effects of AEE on vascular endothelial dysfunction. Both the high-fat diet (HFD)-induced atherosclerotic rat model and the H2O2-induced human umbilical vein endothelial cells (HUVECs) model were used to investigate the effects of AEE on vascular endothelial dysfunction. UPLC/QTOF-MS coupled with a multivariate data analysis method were used to profile the variations in the metabolites of HUVECs in response to different treatments. Pretreatment of HUVECs with AEE significantly ameliorated H2O2-induced apoptosis, the overexpression of E-selectin and VCAM-1, and the adhesion of THP-1 cells. Putative endogenous biomarkers associated with the inhibition of endothelial dysfunction were identified in HUVECs pretreated with AEE in the absence or presence of H2O2, and these biomarkers were involved in important metabolic pathways, including amino acid metabolism, carbohydrate metabolism, and glutathione metabolism. Moreover, in vivo, AEE also significantly reduced vascular endothelial dysfunction and decreased the overexpression of VCAM-1 and E-selectin. Based on our findings, the mechanism underlying the anti-atherosclerotic effects of AEE might be related to a reduction in vascular endothelial dysfunction mediated by ameliorating alterations in metabolism, inhibiting oxidative stress, and decreasing the expression of adhesion molecules.

The relationship of redox signaling with the risk for atherosclerosis.

Oxidative balance plays a pivotal role in physiological homeostasis, and many diseases, particularly age-related conditions, are closely associated with oxidative imbalance. While the strategic role of oxidative regulation in various diseases is well-established, the specific involvement of oxidative stress in atherosclerosis remains elusive. Atherosclerosis is a chronic inflammatory disorder characterized by plaque formation within the arteries. Alterations in the oxidative status of vascular tissues are linked to the onset, progression, and outcome of atherosclerosis. This review examines the role of redox signaling in atherosclerosis, including its impact on risk factors such as dyslipidemia, hyperglycemia, inflammation, and unhealthy lifestyle, along with dysregulation, vascular homeostasis, immune system interaction, and therapeutic considerations. Understanding redox signal transduction and the regulation of redox signaling will offer valuable insights into the pathogenesis of atherosclerosis and guide the development of novel therapeutic strategies.

Relative peripheral refraction in school children with different refractive errors using a novel multispectral refraction topographer.

AIM: To compare relative peripheral refraction (RPR) in Chinese school children with different refractive errors using multispectral refraction topography (MRT). METHODS: A total of 713 eyes of primary school children [172 emmetropia (E), 429 low myopia (LM), 80 moderate myopia (MM), and 32 low hypermetropia (LH)] aged 10 to 13y were analyzed. RPRs were measured using MRT without mydriasis. MRT results showed RPR at 0-15° (RPR 0-15), 15°-30° (RPR 15-30), and 30°-45° (RPR 30-45) annular in the inferior (RPR-I), superior (RPR-S), nasal (RPR-N), and temporal (RPR-T) quadrants. Spherical equivalent (SE) was detected and calculated using an autorefractor. RESULTS: There were significant differences of RPR 15-30 between groups MM [0.02 (-0.12; 0.18)] and LH [-0.13 (-0.36; 0.12)] (P<0.05), MM and E [-0.06 (-0.20; 0.10)] (P<0.05), and LM [-0.02 (-0.15; 0.15)] and E (P<0.05). There were also significant differences of RPR 30-45 between groups MM [0.45 (0.18; 0.74)] and E [0.29 (-0.09; 0.67)] (P<0.05), and LM [0.44 (0.14; 0.76)] and E (P<0.001). RPR values increased from the hyperopic to medium myopic group in each annular. There were significant differences of RPR-S between groups MM [-0.02 (-0.60; 0.30)] and E [-0.44 (-0.89; -0.04)] (P<0.001), and LM [-0.28 (-0.71; 0.12)] and E (P<0.05). There were also significant differences of RPR-T between groups MM [0.37 (0.21; 0.78)] and LH [0.14 (-0.52; 0.50)] (P<0.05), LM [0.41 (0.06; 0.84)] and LH (P<0.05), and LM and E [0.29 (-0.10; 0.68), P<0.05]. A Spearman's correlation analysis showed a negative correlation between RPR and SE in the 15°-30° (P=0.005), 30°-45° (P<0.05) annular (P=0.002), superior (P<0.001), and temporal (P=0.001) quadrants. CONCLUSION: Without pupil dilation, values for RPR 15-30, 30-45, RPR-S, and T shows significant differences between myopic eyes and emmetropia, and the differences are negatively correlated with SE.

Targeting the stimulator of interferon genes (STING) in breast cancer.

Breast cancer has a high occurrence rate globally and its treatment has demonstrated clinical efficacy with the use of systemic chemotherapy and immune checkpoint blockade. Insufficient cytotoxic T lymphocyte infiltration and the accumulation of immunosuppressive cells within tumours are the primary factors responsible for the inadequate clinical effectiveness of breast cancer treatment. The stimulator of interferon genes (STING) represents a pivotal protein in the innate immune response. Upon activation, STING triggers the activation and enhancement of innate and adaptive immune functions, resulting in therapeutic benefits for malignant tumours. The STING signalling pathway in breast cancer is influenced by various factors such as deoxyribonucleic acid damage response, tumour immune microenvironment, and mitochondrial function. The use of STING agonists is gaining momentum in breast cancer research. This review provides a comprehensive overview of the cyclic guanosine monophosphate-adenosine monophosphate synthase-STING pathway, its agonists, and the latest findings related to their application in breast cancer.

Enrichment of Circulating Tumor Cells of Lung Cancer and Correlation With Serum Leukomonocyte and Tumor Biomarkers: A Retrospective Study.

STUDY DESIGN: Circulating tumor cells is important in the clinical diagnosis of cancer and there are a number of circulating tumor cell detection systems associated with different isolation strategies being validated. There is a novel platform, the CytoBot 2000, which utilizes a combination of physical and immunological technologies to isolate and capture circulating tumor cells. METHODS: In this retrospective study, 39 lung cancer patients and 11 normal healthy individuals were enrolled and performed circulating tumor cell tests and immunofluorescence staining with CytoBot 2000. The performance of this device was assessed by receiver operating characteristic curve. The clinical relevance of circulating tumor cells was assessed by Chi-square. The correlations between circulating tumor cell number and blood lymphocytes and tumor biomarkers were analyzed by Pearson correlation coefficient. RESULTS: The number of circulating tumor cell is significantly increased in lung cancer patients (3.74 > 0.45, P < .0001). The CytoBot 2000 presented a 100% (39/39) circulating tumor cell detection rate in lung cancer patients and 36% (4/11) in healthy individual blood samples, the sensitivity and specificity were 89.7% and 90.9%, respectively, and with the area under curve of 0.966. Further, there was a positive correlation between circulating tumor cell count and carcinoembryonic antigen 211 (R2 = 0.125, P = .027), but not blood lymphocytes (P = .089). CONCLUSIONS: This automatic platform showed excellent performance of circulating tumor cell detection by clinical sample. The tumor biomarkers increased with the number of circulating tumor cell in the lung cancer patients.

Serum Metabolomics Coupling With Clinical Laboratory Indicators Reveal Taxonomic Features of Leukemia.

Metabolic abnormality has been considered to be the seventh characteristic in cancer cells. The potential prospect of using serum biomarkers metabolites to differentiate ALL from AML remains unclear. The purpose of our study is to probe whether the differences in metabolomics are related to clinical laboratory-related indicators. We used LC-MS-based metabolomics analysis to study 50 peripheral blood samples of leukemia patients from a single center. Then Chi-square test and T test were used to analyze the clinical characteristics, laboratory indicators and cytokines of 50 patients with leukemia. Correlation analysis was used to explore the relationship between them and the differential metabolites of different types of leukemia. Our study shows that it is feasible to better identify serum metabolic differences in different types and states of leukemia by metabolomic analysis on existing clinical diagnostic techniques. The metabolism of choline and betaine may also be significantly related to the patient's blood lipid profile. The main enrichment pathways for distinguishing differential metabolites in different types of leukemia are amino acid metabolism and fatty acid metabolism. All these findings suggested that differential metabolites and lipid profiles might identify different types of leukemia based on existing clinical diagnostic techniques, and their rich metabolic pathways help us to better understand the physiological characteristics of leukemia.

Determination of astaxanthin in Haematococcus pluvialis by first-order derivative spectrophotometry.

A highly selective, convenient, and precise method, first-order derivative spectrophotometry, was applied for the determination of astaxanthin in Haematococcus pluvialis. Ethyl acetate and ethanol (1:1, v/v) were found to be the best extraction solvent tested due to their high efficiency and low toxicity compared with nine other organic solvents. Astaxanthin coexisting with chlorophyll and beta-carotene was analyzed by first-order derivative spectrophotometry in order to optimize the conditions for the determination of astaxanthin. The results show that when detected at 432 nm, the interfering substances could be eliminated. The dynamic linear range was 2.0-8.0 microg/mL, with a correlation coefficient of 0.9916. The detection threshold was 0.41 microg/mL. The RSD for the determination of astaxanthin was in the range of 0.01-0.06%; the results of recovery test were 98.1-108.0%. The statistical analysis between first-order derivative spectrophotometry and HPLC by T-testing did not exceed their critical values, revealing no significant differences between these two methods. It was proved that first-order derivative spectrophotometry is a rapid and convenient method for the determination of astaxanthin in H. pluvialis that can eliminate the negative effect resulting from the coexistence of astaxanthin with chlorophyll and beta-carotene.

Interleukin-17A Contributes to Bacterial Clearance in a Mouse Model of Streptococcal Toxic Shock-Like Syndrome.

Streptococcus suis (S. suis), an emerging zoonotic pathogen, can cause streptococcal toxic shock-like syndrome (STSLS) in humans with high mortality. STSLS is characterized by high bacterial burden, an inflammatory cytokine storm, multi-organ dysfunction, and ultimately acute host death. Although it has been found that a significantly high level of IL-17A was induced in an NLRP3-dependent manner during STSLS development, the role of IL-17A on S. suis STSLS remains to be elucidated. In this study, we found that the epidemic strain SC 19 caused a significantly higher level of IL-17A than the non-epidemic strain P1/7. In addition, higher bacterial burden was observed from SC 19-infected il17a-/- mice than il17a+/+ mice, although acute death, tissue injury and inflammatory cytokines storm were observed in both types of mice. Furthermore, compared with il17a+/+ mice, the level of neutrophils recruitment was lower in il17a-/- mice, and the levels of induced antimicrobial proteins, such as CRAMP, S100A8 and lipocalin-2, were also decreased in il17a-/- mice. In conclusion, this study demonstrated that IL-17A does not contribute to the severe inflammation, although it may play a minor role for bacterial clearance by inducing antimicrobial proteins and promoting neutrophil recruitment during STSLS.

MiR-6924-5p-rich exosomes derived from genetically modified Scleraxis-overexpressing PDGFRα(+) BMMSCs as novel nanotherapeutics for treating osteolysis during tendon-bone healing and improving healing strength.

Osteolysis at the tendon-bone interface can impair pullout strength during tendon-bone healing and lead to surgery failure, but the effects of clinical treatments are not satisfactory. Mesenchymal stem cell (MSC)-derived exosomes have been used as potent and feasible natural nanocarriers for drug delivery and have been proven to enhance tendon-bone healing strength, indicating that MSC-derived exosomes could be a promising therapeutic strategy. In this study, we explored Scleraxis (Scx) dynamically expressed in PDGFRα(+) bone marrow-derived mesenchymal stem cells (BMMSCs) during natural tendon-bone healing. Then, we investigated the role of PDGFRα(+) BMMSCs in tendon-bone healing after Scx overexpression as well as the underlying mechanisms. Our data demonstrated that Scx-overexpressing PDGFRα(+) BMMSCs (BMMSCScx) could efficiently inhibit peritunnel osteolysis and enhance tendon-bone healing strength by preventing osteoclastogenesis in an exosomes-dependent manner. Exosomal RNA-seq revealed that the abundance of a novel miRNA, miR-6924-5p, was highest among miRNAs. miR-6924-5p could directly inhibit osteoclast formation by binding to the 3'-untranslated regions (3'UTRs) of OCSTAMP and CXCL12. Inhibition of miR-6924-5p expression reversed the prevention of osteoclastogenic differentiation by BMMSCScx derived exosomes (BMMSCScx-exos). Local injection of BMMSCScx-exos or miR-6924-5p dramatically reduced osteoclast formation and improved tendon-bone healing strength. Furthermore, delivery of miR-6924-5p efficiently inhibited the osteoclastogenesis of human monocytes. In brief, our study demonstrates that BMMSCScx-exos or miR-6924-5p could serve as a potential therapy for the treatment of osteolysis during tendon-bone healing and improve the outcome.

Physiological regulation of reactive oxygen species in organisms based on their physicochemical properties.

Oxidative stress is recognized as free radical dyshomeostasis, which has damaging effects on proteins, lipids and DNA. However, during cell differentiation and proliferation and other normal physiological processes, free radicals play a pivotal role in message transmission and are considered important messengers. Organisms maintain free radical homeostasis through a sophisticated regulatory system in which these "2-faced" molecules play appropriate roles under physiological and pathological conditions. Reactive oxygen species (ROS), including a large number of free radicals, act as redox signalling molecules in essential cellular signalling pathways, including cell differentiation and proliferation. However, excessive ROS levels can induce oxidative stress, which is an important risk factor for diabetes, cancer and cardiovascular disease. An overall comprehensive understanding of ROS is beneficial for understanding the pathogenesis of certain diseases and finding new therapeutic treatments. This review primarily focuses on ROS cellular localization, sources, chemistry and molecular targets to determine how to distinguish between the roles of ROS as messengers and in oxidative stress.

Serum Metabolomics Revealed the Differential Metabolic Pathway in Calves with Severe Clinical Diarrhea Symptoms.

The complex etiology, higher morbidity and mortality, poor prognosis, and expensive cost of calf diarrhea have made it a catastrophic disease in the dairy industry. This study aims to assess the biomarkers in calves with diarrhea and to predict the biomarkers related to the pathway. As subjects, nine calves with diarrhea and nine healthy calves were enrolled, according to strict enrollment criteria. The serum metabolites were detected by a liquid chromatographic tandem mass spectrometry (LC-MS/MS), and then analyzed by online multivariate statistical analysis software to further screen the biomarkers. In addition, the biomarkers involved in the metabolic pathways of calves with diarrhea and healthy calves were analyzed. In the serum of calves with diarrhea, nine biomarkers were found to which several biomarkers exhibited a certain relation. Moreover, these biomarkers were involved in important metabolic pathways, including protein digestion and absorption, ABC transporters, aminoacyl-tRNA biosynthesis, mineral absorption, and fatty acid biosynthesis. All these findings suggested that the imbalance of these markers was closely related to the occurrence and development of calf diarrhea. The targeted regulation of metabolic pathways involved in these biomarkers may facilitate the diagnosis, treatment, and discussion of the mechanism of calf diarrhea.

Aspirin Eugenol Ester Attenuates Paraquat-Induced Hepatotoxicity by Inhibiting Oxidative Stress.

Aspirin eugenol ester (AEE) is a new potential drug with anti-inflammatory and antioxidant stress pharmacological activity. Paraquat (PQ) is an effective and commercially important herbicide that is widely used worldwide. However, paraquat is highly toxic and can cause various complications and acute organ damage, such as liver, kidney and lung damage. The purpose of this study was to investigate whether AEE has a protective effect on hepatotoxicity induced by PQ in vivo and in vitro. Cell viability, apoptosis rate, mitochondrial function and intracellular oxidative stress were detected to evaluate the protective effect of AEE on PQ-induced BRL-3A (normal rat hepatocytes) cytotoxicity in vitro. In vivo, AEE pretreatment could attenuate oxidative stress and histopathological changes in rat liver induced by PQ. The results showed that AEE could reduce the hepatotoxicity induced by PQ in vivo and in vitro. AEE reduced PQ-induced hepatotoxicity by inhibitingoxidative stress and maintaining mitochondrial function. This study proved that AEE is an effective antioxidant and can reduce the hepatotoxicity of PQ.

Aspirin Eugenol Ester Protects Vascular Endothelium From Oxidative Injury by the Apoptosis Signal Regulating Kinase-1 Pathway.

Aspirin eugenol ester (AEE) is a new potential pharmaceutical compound possessing anti-inflammatory, anti-cardiovascular disease, and antioxidative stress activity. The pharmacological activities of AEE are partly dependent on its regulation of cell apoptosis. However, it is still unclear how AEE inhibits cell apoptosis on the basis of its antioxidative stress effect. This study aimed to reveal the vascular antioxidative mechanism of AEE in response to H2O2-induced oxidative stress in HUVECs and paraquat-induced oxidative stress in rats. In the different intervention groups of HUVECs and rats, the expression of ASK1, ERK1/2, SAPK/JNK, and p38 and the phosphorylation levels of ERK1/2, SAPK/JNK, and p38 were measured. The effects of ASK1 and ERK1/2 on the anti-apoptotic activity of AEE in the oxidative stress model were probed using the corresponding inhibitors ASK1 and ERK1/2. The results showed that in the HUVECs, 200 µM H2O2 treatment significantly increased the phosphorylation of SAPK/JNK and the level of ASK1 but decreased the phosphorylation of ERK1/2, while in the HUVECs pretreated with AEE, the H2O2-induced changes were significantly ameliorated. The findings were observed in vitro and in vivo. Moreover, inhibition of ASK1 and ERK1/2 showed that ASK1 plays a vital role in the protective effect of AEE on H2O2-induced apoptosis. All findings suggested that AEE protects the vascular endothelium from oxidative injury by mediating the ASK1 pathway.

Liver Metabolomics Reveals the Effect of Lactobacillus reuteri on Alcoholic Liver Disease.

Alcoholic liver disease (ALD), a type of chronic liver disease that is prevalent worldwide, is still identified to have a poor prognosis despite many medical treatment protocols. Thus, it is urgent to develop and test new treatment protocols for ALD. Lactobacillus reuteri (L. reuteri) has been widely used in the clinical treatment of digestive system diseases, but studies on the protective effect of L. reuteri on ALD are considered to be rare. Therefore, in the present study, we examined the effect of L. reuteri on ALD and provide data that are significant in the development of new treatment protocols for ALD. An ALD model has been established in C57BL/6J mice treated according to the Gao-binge modeling method. Mice in the treatment group were administered with L. reuteri. Hematoxylin and eosin (H&E) staining, oil red O staining, immunohistochemistry, and biochemical analyses were performed to detect the phenotypic changes in the liver among mice in the different treatment groups. L. reuteri treatment reversed inflammatory cell infiltration and lipid accumulation. Moreover, AST, ALT, TG, and TCH levels were also reduced in the probiotics-treatment group. Five candidate biomarkers were found in the liver metabolites of different treatment groups by UPLC/QTOF-MS and a multivariate analysis. Several fatty acid metabolic pathways such as linoleic acid metabolism and glycerolipid metabolism were involved. All these findings suggested that L. reuteri treatment reversed the phenotype of ethanol-induced hepatitis and metabolic disorders. These findings provide evidence that L. reuteri might serve as a new therapeutic strategy for ALD.

Aspirin Eugenol Ester Reduces H2O2-Induced Oxidative Stress of HUVECs via Mitochondria-Lysosome Axis.

The oxidative stress of vessel endothelium is a major risk factor of cardiovascular disorders. Antioxidative stress drugs are widely used in cardiovascular therapy. Aspirin eugenol ester (AEE) is a new pharmaceutical compound synthesized by esterification reaction of aspirin with eugenols and possesses antioxidative activity. The present study was designed to investigate the mechanism how AEE protects human umbilical vein endothelial cells (HUVECs) from H2O2-induced oxidative stress. H2O2 was given to the HUVECs with or without AEE pretreatment. Changes in the oxidative stress-related factors, including those related to the mitochondria-lysosome axis, were determined with Western blotting, cellular immunofluorescence, and enzyme activity test. The results showed that, in the HUVECs, 300 µM H2O2 treatment significantly increased the apoptosis rate, MDA concentration, reactive oxygen species (ROS) production, mitochondrial membrane potential, expression of Bax and mature cathepsin D (CTSD), and activity of CTSD and Caspase3 (Cas3) but decreased the expression of Bcl2 and lysosomal membrane stability, while in the HUVECs pretreated with AEE, the above changes caused by either the stimulatory or the inhibitory effect of H2O2 on the relevant factors were significantly reduced. AEE pretreatment significantly enhanced the activity of cellular superoxide dismutase and glutathione peroxidase in the HUVECs. Our findings suggest that AEE effectively reduced H2O2-induced oxidative stress in the HUVECs via mitochondria-lysosome axis.

Aspirin eugenol ester attenuates oxidative injury of vascular endothelial cells by regulating NOS and Nrf2 signalling pathways.

BACKGROUND AND PURPOSE: Aspirin eugenol ester (AEE) is a new drug compound synthesized by combining aspirin with eugenol. It was reported to possess anti-thrombotic, anti-atherosclerotic, and anti-oxidative effects. However, its molecular mechanism against oxidative injury is unclear. This study investigated how AEE affected the oxidative injury of vascular endothelial cells in vivo and in vitro. EXPERIMENTAL APPROACH: A hamster model of atherosclerosis induced by a high fat diet (HFD) and an in vitro model of oxidative stress, H2 O2 -induced apoptosis of HUVECs, were used to investigate the anti-oxidative effects of AEE. KEY RESULTS: AEE significantly reduced the stimulatory effect of HFD on malondialdehyde, the inhibitory effect of HFD on SOD activity and GSH/GSSG ratio, and the overexpression of inducible NOS (iNOS) in the aorta. In vitro, incubation of HUVECs with H2 O2 led their apoptosis, dysfunctions of the NO systems (including increased iNOS activity, decreased endothelial NOS activity, and increased production of NO), an imbalance in calcium homeostasis and energy metabolism with an increase in intracellular free calcium and decrease in ATP, and a down-regulation of Nrf2. In contrast, in the HUVECs pretreated with 1 µM AEE for 24 hr, the above adverse effects induced by H2 O2 were significantly ameliorated. Moreover, the decrease in NO production and activity of iNOS induced by AEE was significantly attenuated in Nrf2-inhibited HUVECs. CONCLUSION AND IMPLICATION: AEE protects vascular endothelial cells from oxidative injury by regulating NOS and Nrf2 signalling pathways. This suggests that AEE is a novel potential agent for the prevention of atherosclerosis.

CALB1 enhances the interaction between p53 and MDM2, and inhibits the senescence of ovarian cancer cells.

Numerous studies have demonstrated the association between senescence and cancer. However, the molecular mechanism regulating senescence in ovarian cancer remains unknown. In the present study, the protein expression level of calbindin 1 (CALB1) in ovarian cancer was examined using western blot and immunohistochemistry. The function of CALB1 in ovarian cancer cells was examined using MTT assay, anchorage­independent growth assay and senescence assay. The molecular mechanisms underlying CALB1 function were investigated using immunoprecipitation and pull­down assays. In the present study, the expression of CALB1 was found to be increased in ovarian cancer. Overexpression of CALB1 promoted the proliferation and colony formation of ovarian cancer cells and inhibited senescence by modulating the expression levels of p21 and p27. Knockdown of CALB1 inhibited the proliferation and colony formation of ovarian cancer cells. Mechanistically, co­immunoprecipitation assays revealed that CALB1 interacts with MDM2 proto­oncogene (MDM2) and promoted the interaction between p53 and MDM2. Collectively, the present study suggested that CALB1 may act as an oncogene in ovarian cancer by inhibiting the p53 pathway.

Effect of atorvastatin preconditioning on hyperglycemia induced hemorrhagic transformation in mice after cerebral ischemia / 中华老年心脑血管病杂志

Objective To investigate the role and underlying mechanism of atorvastatin on hyper-glycemia induced hemorrhagic transformation(HT)in a mouse model of cerebral ischemia.Meth-ods A total of 36 SPF-grade male C57BL/6 mice were randomly divided into sham operation group,HT model group and atorvastatin group,with 12 mice in each group.HE staining was used to observe cerebral hemorrhage,immunofluorescent staining was employed to detect the integrity of blood-brain barrier,and Western blotting was applied to measure the protein expression of IgG,ZO-1,occludin,claduin5,MMP-2 and-9 in ischemic penumbra brain tissues.Results Com-pared with sham operation group,the neurological deficit score,mortality rate,HT incidence,HT grading score,IgG fluorescence intensity,and protein levels of IgG,MMP-2 and-9 were signifi-cantly increased,while the protein levels of ZO-1,occludin and claudin5 were obviously decreased in the HT model group(P＜0.01).Atorvastatin treatment resulted in significantly lower neuro-logical deficit score(2.73±1.19 vs 3.91±0.94),mortality rate(16.7％vs 41.6％),HT incidence(58.3％vs 91.6％),HT grading score(1.00±1.04 vs 2.58±1.13),IgG fluorescence intensity(504.30±105.52 a.u vs 859.91±153.28 a.u),and protein levels of IgG(4.55±1.40 vs 12.06± 3.73),MMP-2(1.87±0.41 vs 2.95±0.68)and-9(1.47±0.24 vs 2.12±0.23)(P＜0.05,P＜0.01),and increased protein levels of ZO-1(1.55±0.20 vs 0.53±0.10),occludin(0.92±0.11 vs 0.35±0.07)and claudin5(0.58±0.04 vs 0.30±0.05)(P＜0.01)when compared with the HT model group.Conclusion Atorvastatin can reduce the permeability of blood-brain barrier by in-hibiting the activation of MMP-2 and MMP-9 and up-regulating the protein levels of ZO-1,occlu-din and claudin5,and thus attenuate hyperglycemia-induced HT.