Development in biomarkers of breast cancer: a bibliometric analysis from 2011 to 2020.

OBJECTIVE: Breast cancer (BC) is a prevalent cancer all over the world. We conducted a bibliometric study to analyze global scientific results over the past 10 years, including the hotspots and frontiers of biomarker research in BC. MATERIALS AND METHODS: From 2011 to 2020, literature research from the Web of Science Core Collection (WoSCC) was performed. VOSviewer was applied to analyze and visualize the frontiers and hotspots related to biomarker research in BC. RESULTS: 13,680 papers were retrieved. There was an increasing number of annual publications (Np) related to biomarkers in BC during the past decade. The United States (US) published the greatest number of papers, which had the highest number of citations (Nc) and ranked first in terms of H-index. PLoS One and the University of Texas System were the most productive journals and affiliations, respectively. In 2014, Chetan Bettegowda published a paper with the world's highest global citation score (GCS). In recent years, keywords such as "expression", "microRNA", and "cell" have appeared most frequently. In addition, research related to COVID-19 in this field has become a hot topic in recent years. This bibliometric study found an increasing trend in publications related to biomarkers in British Columbia and the US was found to be an influential producer in this field. CONCLUSIONS: In the past decade, most research has focused on basic and clinical studies, of which microRNAs (miRNAs) and circulating tumor DNAs (ctDNAs) associated with the inhibition and attenuation of BC have become the focus of recent research.

Modular characteristics and mechanism of action of herbs for vascular calcification treatment in Chinese medicine: a data mining and network pharmacology-based identification.

OBJECTIVE: The aim of this study was to investigate the modular characteristics and mechanism of action of Chinese herbs for vascular calcification (VC) treatment. MATERIALS AND METHODS: Network pharmacology coupled with literature data mining was utilized to assess the Chinese herbal clinical performance as well as its similarity, characteristics, ingredient, target, and Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and network construction. RESULTS: The top 15 medications from the literature, according to the usage, and 190 active chemicals, 183 common targets between medication and VC-related targets were weeded out. Analysis of the relationships between the active ingredients, pharmacological targets, and signaling pathways helped to clearly define the therapeutic effect of Traditional Chinese Medicine (TCM). Importantly, we discovered seven most hub proteins (AKT1, CTNNB1, TNF, EGFR, TP53, JUN and IL-6) and two of the herbs' most fundamental ingredients (Formononetin and Luteolin) in TCM-mediated VC suppression. Mechanistically, the metabolic pathways [AGE-RAGE pathway, interleukin-17 (IL-17) pathway, and p53 pathway] as well as smooth muscle adaptation (functional remodeling) and oxidoreductase activity (redox homeostasis modulating) are also crucially implicated. CONCLUSIONS: Our work, accomplished by network pharmacology and data mining, increases our understanding of TCM in VC therapy and may offer insightful information for future drug discovery investigations.

Clinical practice of traditional Chinese medicine for the treatment of postmenopausal osteoporosis: a literature review.

OBJECTIVE: This study aimed to evaluate the effectiveness and safety of traditional Chinese medicine (TCM) for postmenopausal osteoporosis (PMOP). METHODS: We conducted a computer literature search in five databases and comprehensively extracted all kinds of information from each article. Traditional Chinese medicine inheritance support system (TCMISS) V2.5 was adopted to perform association analysis. The effectiveness, safety and methodological quality were analyzed using randomized controlled clinical trials (RCTs). RESULTS: A total of 2880 related articles were collected. Finally, 423 articles which included 312 RCTs were included for in-depth analysis. We collected 369 Chinese medicine prescriptions and found that the top three frequently used herbs in the treatment of PMOP were Epimedii Folium (Yinyanghuo), Rehmanniae Radix Praeparata (Shudihuang) and Angelicae Sinensis Radix (Danggui). The top Chinese patent medicine was Gushukang capsule. No serious adverse reaction (AR) had been reported in the Chinese medical treatment group. CONCLUSION: The effectiveness of TCM in treating PMOP needs to be further explored, and the safety is good. Therefore, high-quality evidence is urgently needed to supplement.

Honey combined with silver ion dressing in complicated chronic wound of the scalp: a case report.

OBJECTIVE: Scalp wound healing is a complex process. Nonhealing wounds can become chronic wounds, which increase the trauma and economic burden on a patient and may even cause death in severe cases. Thus, it can be difficult to find an effective treatment for chronic wounds of the scalp. CASE PRESENTATION: We present a case of a 13-year-old female patient with a chronic wound caused by a scalp incision infection 3 months after two operations for craniotomy for arachnoid cyst resection and cystic lesion-cisterna magna drainage. After repeated dressing changes and two debridement operations, the incision had still not healed during the following year. The wound finally healed after 6 months of dressing changes by combining honey with silver ion dressings, and the incision had not re-ruptured after 10 months of follow-up. CONCLUSIONS: Honey combined with silver may be an effective method for the treatment of chronic scalp wounds.

Local anesthesia with sedation and general anesthesia for the treatment of chronic subdural hematoma: a systematic review and meta-analysis.

OBJECTIVE: Drilling and drainage is the main treatment for chronic subdural hematoma (cSDH). However, anesthesia methods also have an important effect on patients' postoperative outcomes. The clinical effect of drainage of cSDH under local anesthesia with sedation (LAS) and general anesthesia (GA) was systematically evaluated. MATERIALS AND METHODS: A literature study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for studies that compare LAS and GA for cSDH. The following treatment outcomes were compared between LAS and GA: total duration of surgery, postoperative complications, mortality, recurrence rate, and hospital length of stay (LOS). RESULTS: Four papers (n = 391, LAS: 196, GA: 195) met the inclusion criteria. Although there was no statistically significant difference between the two groups in mortality (OR: 0.47, 95% CI: 0.06-3.84, p = 0.48; p = 0.2, I2 = 39%), recurrence rate (OR: 0.82, 95% CI: 0.33-2.04, p = 0.66; p = 0.69, I2 = 0%), LOS (ratio of means: 0.86, 95% CI: 0.71-1.05, p = 0.14; p = 0.02, I2 = 75%). The total duration of surgery (MD: -26.71 min, 95% CI: -37.29 to -16.13, p < 0.00001; p = 0.65, I2 = 0%) was significantly shorter and the number of postoperative complications was significantly lower in the LAS group compared with the GA group (OR: 0.25, 95% CI: 0.13-0.50, p < 0.0001; p= 0.62, I2 = 0%). CONCLUSIONS: A systematic review and meta-analysis of the existing literature showed that LAS reduces the total duration of surgery and postoperative complications compared to GA. No significant difference in mortality, recurrence rate, and LOS was observed between the two groups.

Is sudden deafness in non-diabetic patients affected by their glycosylated hemoglobin levels?

OBJECTIVE: Though the incidence of sudden sensorineural hearing loss (SSNHL) is relatively low, the disorder has a major impact on the quality of life of patients. Identifying biological markers for the disease will be useful, especially in resource-scarce areas. Our study aims to evaluate the correlation between the degree of hearing impairment and glycosylated hemoglobin (HbA1c) in patients with SSNHL. PATIENTS AND METHODS: One hundred and thirty-eight patients with SSNHL and no history of diabetes were included in this study. The intravenous HbA1c content before treatment was correlated with the pure tone audiogram (PTA) average as per the criteria for SSNHL. Spearman correlation and the Receiver Operating Characteristic (ROC) curve were used to determine the HbA1c levels of the study participants. The critical value of HbA1c and its diagnostic implications for assessing the degree of hearing impairment in patients with SSNHL were noted. RESULTS: There was a significant positive correlation between HbA1c and PTA in patients with SSNHL (p<0.05). In addition, the best HbA1c cutoff value for screening and referring an individual for a detailed audiometric evaluation of hearing impairment was 5.550%, as indicated by the ROC curve. CONCLUSIONS: The level of HbA1c in the circulation may affect the onset, duration, and progression of SSNHL. The same parameter may be used as a diagnostic and prognostic indicator for this condition.

Protective effects of L-carnitine on reproductive capacity in rats with diabetes.

To explore the protective effects of L-carnitine on erectile function and reproductive function in rats with diabetes. A total of 60 male diabetes mellitus induced-erectile dysfunction (DMED) rats were randomly divided into three groups, 20 rats in each group. The blank group was fed normally, the control group was fed with 0.9% sodium chloride solution 5 ml/kg/day, and the experimental group was given L-carnitine 300 mg/kg/day. After six weeks, the Corpus cavernosum penis pressure (ICP) and mean arterial pressure (MAP) were measured. The sperm of epididymis were taken to detect the parameters of sperm. After six weeks of treatment, ICP and MAP in the experimental group were significantly higher than those in the control group and blank group (p < 0.05), and sperm density and PR in the experimental group were significantly higher than those in the control group and the blank group (p < 0.05). Superoxide dismutase (SOD) in the experimental group was significantly higher than that in the control group and blank group (p < 0.05). Malondialdehyde (MDA) in the experimental group was significantly lower than that in the control group and blank group (p < 0.05). The follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone in the experimental group were significantly higher than those in the control group and blank group (p < 0.05). We conclude that L-carnitine can significantly improve erectile function and reproductive function in rats with diabetes and it has great potential in the treatment of systemic organ damage in DMED rats.

Comparative assessment of gut microbial composition and function in patients with Graves' disease and Graves' orbitopathy.

BACKGROUND: A previous study indicated that gut microbiota changed notably in Graves' orbitopathy (GO) patients as compared to controls. However, the characteristics of intestinal bacteria in Graves' disease (GD) and GO are unclear. OBJECTIVE: The present study aimed to identify specific intestinal bacteria of GD and GO, respectively. METHODS: The gut microbial communities of the fecal samples of 30 GD patients without GO, 33 GO subjects, and 32 healthy subjects were analyzed and compared by 16S rRNA gene sequencing. RESULTS: At the phylum level, the proportion of Deinococcus-Thermus and Chloroflexi was decreased significantly in GO patients as compared to GD. At the genus level, the proportion of Subdoligranulum and Bilophila was increased while that of Blautia, Anaerostipes, Dorea, Butyricicoccus, Romboutsia, Fusicatenibacter, unidentified_ Lachnospiraceae, unidentified_Clostridiales, Collineslla, Intestinibacter, and Phascolarctobacterium was decreased in the GO group as compared to the GD group. Random forest analysis was used for the identification of specific intestinal microbiota, and Deinococcus-Thermus, Cyanobacteria and Chloroflexi were ranked in the top ten according to their contributions to sample classification. Moreover, compared to the control, there were multiple gut bacterial enrichment metabolic pathways in GO and GD patients, including nucleotide metabolism, enzyme family, and energy metabolism. Compared to GO, the only enrichment metabolic pathway found in GD was the viral protein family. CONCLUSIONS: This study highlighted the significant differences in the intestinal microbiota and predictive functions of GD with GO, thereby providing new insights into the role of the gut bacteria that might contribute to the development of GO in GD patients.

Lipopolysaccharide-stimulated bone marrow mesenchymal stem cells-derived exosomes inhibit H2O2-induced cardiomyocyte inflammation and oxidative stress via regulating miR-181a-5p/ATF2 axis.

OBJECTIVE: Myocardial infarction (MI) is a cardiovascular disease that seriously endangers human health. Exosomes secreted by stem cells have big potential for the treatment of many diseases. The purpose of this study was to study the therapeutic effects of exosomes derived from lipopolysaccharide (LPS)-stimulated bone marrow mesenchymal stem cells (BMSCs) on MI. PATIENTS AND METHODS: The surface markers of BMSCs were detected by Western blot. After BMSCs were stimulated with LPS for 2 days, the exosomes secreted by BMSCs were extracted and observed by transmission electron microscopy (TEM), and their specific surface markers were detected by Western blot. H9c2 cells were co-cultured with exosomes for 24 hours, and then, treated with H2O2 for 4 hours. Next, H9c2 cells were transfected with miRNA-181a-5p mimic (MIM) or negative control (NC). Inflammation and oxidative stress of H9c2 cells were detected by Western blot, cell staining, reactive oxygen species (ROS) quantification, and SOD activity assay. At last, miR-181a-5p expression in BMSCs, exosomes, and H9c2 cells was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). RESULTS: The results revealed that the expression of miR-181a-5p was increased in LPS-stimulated BMSCs (L-BMSC) and in their secreted exosomes. Besides, the expressions of TNF-α and IL-1ß were decreased, while those of SOD1 and SOD2 were increased in H9c2 cells co-cultured with exosomes secreted by LPS-stimulated BMSCs (L-EXO) and transfected with MIM. Moreover, the fluorescence intensity of IL-1ß immunofluorescence was decreased in H9c2 cells co-cultured with L-EXO or transfected with MIM. The level of ROS was also decreased in H9c2 cells co-cultured with L-EXO or transfected with MIM. Furthermore, miR-181a-5p was found to target ATF2 through target gene prediction databases and Western blot and Dual-Luciferase reporter assays. CONCLUSIONS: LPS stimulation can increase the expression of miR-181a-5p in BMSCs, and miR-181a-5p inhibits myocardial inflammation and oxidative stress by targeting ATF2.

MicroRNA-448/EPHA7 axis regulates cell proliferation, invasion and migration via regulation of PI3K/AKT signaling pathway and epithelial-to-mesenchymal transition in non-small cell lung cancer.

OBJECTIVE: Non-small cell lung cancer (NSCLC) is a primary subtype of lung cancers which has a high morbidity and poor prognosis. Emerging evidence has demonstrated that aberrantly expressed microRNAs (miRNAs) were implicated in the regulatory functions of multiple processes during tumorigenesis. In the current study, we explored the functional roles and underlying mechanisms of miR-448 in NSCLC. PATIENTS AND METHODS: Quantitative real-time polymerase chain reaction assays were conducted to measure miR-448 expressions in 51 pairs of NSCLC tissues and corresponding normal tissues. Moreover, the relationship between miR-448 expressions and clinicopathological characteristics of NSCLC patients was also determined. We then performed transwell assays to explore the functions of miR-448 in NSCLC cell invasion and migration. As we had identified EPHA7 as a functional target of miR-448 in NSCLC cells, the clinical significance of EPHA7 in NSCLC patients was further investigated. Finally, we detected the influence of miR-448 on tumor growth rate and tumor size of NSCLC using tumor xenografts. RESULTS: Underexpressed miR-448 was identified in NSCLC, and low miR-448 expression was confirmed to be associated with the poor prognosis and adverse clinicopathologic features of NSCLC patients. Moreover, functional assays demonstrated that miR-448 overexpression suppressed NSCLC cell proliferation, invasion and migration. EPHA7 was identified as a direct target of miR-448. Additionally, miR-448 restoration suppressed in vivo NSCLC cell growth. Finally, our studies also indicated that miR-448 exerted anti-NSCLC functions via regulating PI3K/AKT signaling pathway and EMT. CONCLUSIONS: These results showed that miR-448/EPHA7 axis maybe one of the useful diagnostic and prognostic biomarkers for NSCLC patients.

LncRNA HOST2 enhances gefitinib-resistance in non-small cell lung cancer by down-regulating miRNA-621.

OBJECTIVE: The aim of this study was to clarify whether long non-coding RNA (lncRNA) human ovarian cancer-specific transcript 2 (HOST2) could enhance gefitinib-resistance in non-small cell lung cancer (NSCLC) by down-regulating microRNA-621 (miRNA-621). MATERIALS AND METHODS: The relative expression levels of HOST2, miRNA-621 and SYF2 in NSCLC cell lines were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The regulatory effects of HOST2 and miRNA-621 on the proliferative ability and cell cycle of NSCLC cells were evaluated by Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. Meanwhile, the binding relationship between miRNA-621 to HOST2 and SYF2 was verified by Dual-Luciferase reporter gene assay. Furthermore, rescue experiments were conducted to verify whether HOST2 regulated the proliferative ability and cell cycle of NSCLC cells by absorbing miRNA-621 to up-regulate SYF2 level. RESULTS: HOST2 showed significantly greater abundance in gefitinib-resistant PC9 cells (PC9/GR) relative to parental cells. The up-regulation of HOST2 markedly enhanced gefitinib-resistance, the proliferative ability and cell cycle progression of PC9 cells. Subsequent Dual-Luciferase reporter gene assay showed the binding relationship between HOST2 and miRNA-621. Moreover, miRNA-621 was lowly expressed in PC9/GR cells compared with parental cells. Up-regulation of miRNA-621 significantly suppressed the proliferative ability and cell cycle progression, as well as reversed gefitinib-sensitivity of PC9 cells. More importantly, miRNA-621 up-regulation abolished the biological function of HOST2 in NSCLC. SYF2 was confirmed as the target gene of miRNA-621 in the same way. In addition, the overexpression of SYF2 remarkably enhanced gefitinib-resistance, while reversed the inhibitory effects of miRNA-621 on the proliferative ability and cell cycle of NSCLC cells. CONCLUSIONS: HOST2 elevates gefitinib-resistance in NSCLC by degrading miRNA-621 to upregulate SYF2.

PPARγ inhibits breast cancer progression by upregulating PTPRF expression.

OBJECTIVE: Peroxisome proliferator-activated receptor γ (PPARγ) regulates fatty acid storage and glucose metabolism. Recently, PPARγ has been reported to be involved in cancer. The present study reported a PPARγ consensus binding site (AGGTCA) in the ptprf promoter and identified a strong association between PPARγ and PTPRF expression, as well as their tumor suppressor roles in a v-Ha-Ras-induced model of breast cancer. MATERIALS AND METHODS: The prognostic potential of PPARγ was assessed with a KM analysis of raw data from 3,951 breast cancer patients. The expression of PPARγ and PTPRF in the rat breast cancer cell lines was detected by Western blot and qPCR. The impact of PPARγ on cancer cell migration, invasion, and growth was confirmed using cell migration assay, transwell cell invasion assay, tri-dimensional soft agar culture, respectively. The binding of PPARγ with the ptprf promoter was then examined using electrophoretic mobility shift assay. The inhibitory effect of PPARγ on tumor growth was then examined in mouse tumor model in vivo. RESULTS: It was identified that PPARγ expression is lost in the aggressive v-Ha-Ras-induced breast cancer cell line FE1.2 but highly expressed in less malignant FE1.3 cells. Exogenous expression of PPARγ in FE1.2 cells (FE1.2-PPARγhi) resulted in a marked inhibition of proliferation compared with that in FE1.2-Vector control group. FE1.2-PPARγhi cells also exhibited reduced migration, invasion, and colony formation abilities compared with those of the controls. The PPARγ agonist rosiglitazone also suppressed the malignant properties of FE1.2 cells. Protein tyrosine phosphatase receptor F (PTPRF), a downstream target of PPARγ, was markedly induced in FE1.2-PPARγhi cells. A PPARγ consensus binding site (AGGTCA) was identified in the ptprf promoter, and an electrophoretic mobility shift assay confirmed that PPARγ bind to this promoter. Similar to the effect of vector-mediated overexpression of PPARγ, ectopic overexpression of PTPRF in FE1.2 cells led to reduced proliferation. Furthermore, a PPARγ antagonist (GW9662) and PTP inhibitor (NSC87877) abrogated the suppressive function of PPARγ and PTPRF in FE1.2 cells, respectively. PPARγ overexpression or activation suppressed the progression and distant organ metastasis of breast cancer cells in a NOD/SCID mouse model. CONCLUSIONS: These results suggest that PPARγ inhibits tumor cell proliferation, at least in part, through direct regulation of the ptprf gene and that PPARγ is a potential target for breast cancer treatment.

Silence of lncRNA XIST represses myocardial cell apoptosis in rats with acute myocardial infarction through regulating miR-449.

OBJECTIVE: To study the influences of long non-coding ribonucleic acid (lncRNA) X-inactive specific transcript (XIST) on rats with acute myocardial infarction (AMI), and its regulatory mechanism. MATERIALS AND METHODS: A total of 30 Sprague-Dawley rats were randomly assigned into Sham group, Model group, and lncRNA XIST small interfering RNA (XIST siRNA) group. The AMI rat model was prepared through ligating the left anterior descending coronary artery. The left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular systolic diameter (LVDs), and left ventricular diastolic diameter (LVDd) of rats were determined using a color Doppler ultrasound system. Reverse transcription-polymerase chain reaction was performed to measure the expression levels of lncRNA XIST, microRNA (miR)-449, and Notch1 in rat heart tissues in each group. Pathological morphology of rat heart tissues in each group was observed via hematoxylin-eosin (HE) staining. Cell apoptosis in rat heart tissues was evaluated through terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. RESULTS: Compared with those in Sham group, rats in Model group had significantly increased LVEDV, LVESV, LVDs, and LVDd. After transfection with lncRNA XIST siRNA, XIST level in rat heart tissues was remarkably declined in XIST siRNA group compared with that in Model group. According to HE staining results, the pathological injuries in rat heart tissues were greatly improved in XIST siRNA group compared with those in Model group. TUNEL staining results revealed that the apoptosis rate of cells in rat heart tissues in XIST siRNA group was markedly lower than that in Model group. Higher level of miR-449 and lower level of Notch1 were observed in rats of XIST siRNA group than those of Model group. CONCLUSIONS: Knockdown of lncRNA XIST can repress the myocardial cell apoptosis in AMI model rats by downregulating miR-449 level.

CX3CR1 participates in pulmonary angiogenesis in experimental hepatopulmonary syndrome mice through inhibiting AKT/ERK signaling pathway and regulating NO/NOS release.

OBJECTIVE: Hepatopulmonary syndrome (HPS) is a kind of pulmonary microvascular disease and occurs in 15%-30% cirrhosis. This study aimed to investigate the effects of pulmonary CX3CR1 on angiogenesis and associated mechanisms in HPS animal models. MATERIALS AND METHODS: CX3CR1GFP/GFP mice were constructed by replacing CX3CR1 with GFP. Common bile duct ligation (CBDL) mouse model was established with surgery. Release of nitric oxide (NO) was evaluated. Hematoxylin-eosin (HE) staining was employed to examine the inflammation of lung tissues. CD31 expression was detected with immunohistochemistry assay. Western blotting was used to evaluate the expression of CX3CL1, CX3CR1, phosphorylated-AKT (p-AKT), phosphorylated-ERK (p-ERK). Quantitative Real Time-PCR (qRT-PCR) assay was used to examine VEGF, PDGF, iNOS, eNOS, and HO-1 expression. RESULTS: CX3CR1-deficiency (CX3CR1GFP/GFP-sham or CX3CR1GFP/GFP-CBDL mice) significantly reduced NO release compared to wide type (WT)-mice or WT-CBDL mice (p<0.05). CX3CR1-deficiency significantly alleviated inflammation compared to wide type (WT)-mice or WT-CBDL mice (p<0.05). CX3CR1-deficiency significantly reduced CD31 expression compared to WT-sham and WT-CBDL mice, respectively (p<0.05). CX3CR1 also participated in anti-angiogenesis efficacy of Bevacizumab. CX3CR1-deficiency significantly down-regulated the ratio of p-AKT/AKT and p-ERK/ERK and inhibited the secretion of VEGF and PDGF compared to WT-mice (p<0.05). CX3CR1-deficiency significantly reduced iNOS, eNOS, and HO-1 expression compared to WT-mice (p<0.05). CONCLUSIONS: CX3CR1 deficiency reduced VEGF and PDGF production, inhibited p-AKT, and p-ERK activation and down-regulated iNOS, eNOS, and HO-1 expression. Therefore, CX3CR1 participates in pulmonary angiogenesis in the experimental HPS mice via inhibiting AKT/ERK signaling pathway and regulating NO/NOS release. These findings would provide a potential insight for clarifying the pathological mechanisms of HPS.

Nodal mitigates cerebral ischemia-reperfusion injury via inhibiting oxidative stress and inflammation.

OBJECTIVE: Nodal is a member of the transforming growth factor ß (TGF-ß) family, which induces the activation of the cytoplasmic Smad2 and Smad3, both of which play a neuroprotective role against cerebral ischemia-reperfusion (I/R) injury. However, the  role of Nodal in cerebral I/R is unclear. Thus, the aim of the present study was to shed light on the function of Nodal in cerebral I/R injury. MATERIALS AND METHODS: Cerebral I/R injury was induced in the Sprague Dawley (SD) rats by middle cerebral artery occlusion (MCAO) and reperfusion and in murine hippocampal neuronal cells (HT22) by oxygen-glucose deprivation/reperfusion (OGD/R) stimulation. The lentivirus vectors (Nodal overexpressing lentivirus vector [OE-Nodal] and the short hair RNA of Nodal [sh-Nodal]) were used to upregulate and downregulate Nodal in SD rats or cells. RESULTS: Nodal expression increased in the cerebral I/R models and reached a peak after 12 h of reperfusion. OE-Nodal administration to the cerebral I/R rats significantly reduced the cerebral infarction volume and inhibited the brain cell apoptosis. It also increased the level of superoxide dismutase (SOD), an antioxidant enzyme, and decreased the levels of the lipid peroxides (malondialdehyde [MDA] and lactate dehydrogenase [LDH]), in addition to those of the proinflammatory factors. Consistently, the upregulation of Nodal in HT22 by OGD/R significantly increased the SOD level and decreased the levels of MDA, LDH, interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α). CONCLUSIONS: This study revealed that Nodal exerted a protective role during cerebral I/R by inhibiting excessive oxidative stress and inflammation.

miR-21 regulates the proliferation and apoptosis of ovarian cancer cells through PTEN/PI3K/AKT.

OBJECTIVE: Phosphatase and tensin homologue deleted on chromosome ten (PTEN) regulates cell proliferation and apoptosis by inhibiting phosphatidylinositol-3 kinase (PI3K) and protein kinase (AKT) signaling. High expression of miR-21 was associated with ovarian cancer. This study aims to investigate whether miR-21 regulates PTEN/PI3K/AKT signaling as well as its role in the proliferation and apoptosis of ovarian cancer cells. MATERIALS AND METHODS: Bioinformatics analysis was used to identify the binding site between miR-21 and the 3'-UTR of PTEN mRNA. A dual-luciferase reporter gene assay was performed to confirm the relationship between miR-21 and PTEN. The expression of miR-21, PTEN, and p-AKT was measured in normal ovarian cell IOSE80, ovarian cancer cell lines A2780, and SKOV3. miR-NC or miR-21 inhibitor was transfected into A2780 or SKOV3 cells followed by the analysis of the expression of miR-21, PTEN, p-AKT, cell apoptosis by flow cytometry, and proliferation by EdU assay. RESULTS: There was a targeted relationship between miR-21 and PTEN. Compared with IOSE80 cell, levels of miR-21 and p-AKT were significantly elevated in A2780 and SKOV3 cells, with the statistical reduction of PTEN expression (p<0.05). The inhibition of miR-21 significantly reduced the expressions of miR-21 and p-AKT and induced PTEN level in A2780 and SKOV3 cells, which also restricted cell proliferation and promoted cell apoptosis. CONCLUSIONS: The miR-21 expression is found elevated in ovarian cancer cells. The suppression of miR-21 increases PTEN expression, inhibits PI3K/AKT activity, promotes cell apoptosis, and reduces cell proliferation. This finding provides new leads to the future treatment of ovarian cancer.

GAS5 promotes myocardial apoptosis in myocardial ischemia-reperfusion injury via upregulating LAS1 expression.

OBJECTIVE: This study aims at investigating whether GAS5 (grow arrest-specific 5) could promote cardiomyocyte apoptosis by upregulating LAS1 expression, thereby participating in the development of myocardial ischemia-reperfusion injury. MATERIALS AND METHODS: The expression level of GAS5 in H9c2 cells after hypoxia/reoxygenation (H/R) treatment was detected by quantitative Real time-polymerase chain reaction (qRT-PCR). Myocardial injury markers in H9c2 cells were evaluated using relative commercial kits, including activities of LDH (lactate dehydrogenase), MDA (malondialdehyde), SOD (superoxide dismutase) and GSH-PX (glutathione peroxidase). Cell proliferation and apoptosis were detected by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. The protein expressions of apoptosis-related genes and p38/MAPK pathway-related genes were detected by Western blot. The regulatory effects of GAS5 on the p38/MAPK pathway were assessed after treatment with p38/MAPK pathway inhibitor in H9c2 cells. RESULTS: QRT-PCR results showed that the expression levels of GAS5 and LAS1 in H/R-treated H9c2 cells were remarkably upregulated compared to those of controls. GAS5 overexpression increased activities of LDH, MDA, SOD and GSH-PX in H/R-treated H9c2 cells. Meanwhile, GAS5 overexpression reduced cell proliferation and apoptosis of H/R-treated cells. Western blot results suggested that the pro-apoptosis genes Bax and cytochrome C were upregulated, whereas the anti-apoptosis gene Bcl-2 was downregulated after GAS5 overexpression. The overexpression of LAS1 in H9c2 cells obtained the same results as GAS5 overexpression. Furthermore, the expressions of p-p38 and p-ERK were upregulated by GAS5 overexpression. SB203580, the p38/MAPK pathway inhibitor, could reverse the inhibited proliferation and increase apoptosis induced by overexpression of GAS5. CONCLUSIONS: GAS5 promotes myocardial apoptosis in myocardial ischemia-reperfusion injury by upregulating LAS1 expression via p38/MAPK pathway. GAS5 may be a potential therapeutic target for myocardial ischemia-reperfusion injury.

Totally thoracoscopic surgery for atrial myxomas resection and atrial septal defect repair.

OBJECTIVE: The purpose of this study is to compare the effectiveness and safety of thoracoscopic surgery and traditional median sternotomy. PATIENTS AND METHODS: 64 patients with atrial myxoma and 114 patients with atrial septal defect were collected from Mar 2012 to Aug 2015. 40 atrial myxoma and 77 atrial septal defect (ASD) patients underwent totally thoracoscopic surgery technique, while 24 atrial myxoma and 37 ASD patients underwent traditional median sternotomy. The baseline characteristics and perioperative data were recorded and analyzed from all cases. Follow-up data were obtained from outpatient clinics. RESULTS: All patients had successful resections or repairs. Compared with the traditional median sternotomy, the patients with atrial myxoma who underwent thoracoscopic surgery had longer operation time (208.08 ± 23.98 vs. 170.00 ± 16.58 min) while shorter intensive care unit (ICU) stay time (17.67 ± 4.95 vs. 49.88 ± 3.21 h), less blood drainage (127.87 ± 48.84 vs. 275.00 ± 59.01 ml) and shorter hospitalization days (9.97 ± 3.54 vs. 15.13 ± 1.06 days). For patients underwent ASD repair, longer operation time (232.92 ± 61.02 vs. 183.40 ± 54.63 min), shorter mechanical assistant ventilation time (4.82 ± 2.10 vs. 6.02 ± 2.50 h) and shorter ICU stay time (18.54 ± 5.80 vs. 39.68 ± 18.44 h) were detected in the thoracoscopic surgery group. There was no postoperative embolism events or death in all participated patients. Neither residual shunt nor atrioventricular blocks were detected in all ASD patients. CONCLUSIONS: Totally thoracoscopic surgery for atrial myxomas and atrial septal defect repair is more effective and safer. It provides another option to treat the patients with atrial myxoma and atrial septal defect.

Serum total bilirubin levels are negatively correlated with metabolic syndrome in aged Chinese women: a community-based study

We evaluated serum total bilirubin levels as a predictor for metabolic syndrome (MetS) and investigated the relationship between serum total bilirubin levels and MetS prevalence. This cross-sectional study included 1728 participants over 65 years of age from Eastern China. Anthropometric data, lifestyle information, and previous medical history were collected. We then measured serum levels of fasting blood-glucose, total cholesterol, triglycerides, and total bilirubin, as well as alanine aminotransferase activity. The prevalence of MetS and each of its individual component were calculated per quartile of total bilirubin level. Logistic regression was used to assess the correlation between serum total bilirubin levels and MetS. Total bilirubin level in the women who did not have MetS was significantly higher than in those who had MetS (P<0.001). Serum total bilirubin quartiles were linearly and negatively correlated with MetS prevalence and hypertriglyceridemia (HTG) in females (P<0.005). Logistic regression showed that serum total bilirubin was an independent predictor of MetS for females (OR: 0.910, 95%CI: 0.863–0.960; P=0.001). The present study suggests that physiological levels of serum total bilirubin might be an independent risk factor for aged Chinese women, and the prevalence of MetS and HTG are negatively correlated to serum total bilirubin levels.

Down-regulation of miR-144 after Mycobacterium tuberculosis infection promotes inflammatory factor secretion from macrophages through the Tpl2/ERK pathway.

Pulmonary tuberculosis is one of the deadliest human diseases and mainly occurs when the immune system is impaired. MicroRNAs (miRNAs) have a critical role in regulating innate and adaptive immunity. Based on previous reports that Mycobacterium tuberculosis (M.tb) can modulate host cell miRNA expression, this study aimed to investigate expression changes in miR-144 and miR-144 regulate macrophage function via targeting of tumor progression locus 2 (Tpl2, also named MAP3K8) and extracellular signal-regulated kinase (ERK) signaling. I examined the miRNA expression profile of M.tb-infected monocyte-derived macrophages (MDMs) by gene expression profiling and quantitative real-time PCR (qRT-PCR). miR-144 is obviously down-regulated in MDMs infected with M.tb and directly binds to the 3'-UTR of Tpl2, acting as a negative regulator. Moreover, inhibiting miR-144 or over-expression of Tpl2 can activate the ERK signaling pathway by inducing ERK1/2 phosphorylation. At the same time, TNF-α, IL-1ß and IL-6 secretion were significantly accelerated. Taken together, these results suggest that miR-144 is expressed at a low level in M.tb-infected MDMs and acts as a negative regulator for Tpl2 target, which is closely connected with ERK signaling that regulates inflammatory factor secretion.