Predictive value of atherogenic index of plasma and atherogenic index of plasma combined with low-density lipoprotein cholesterol for the risk of acute myocardial infarction.

Background and aims: Acute myocardial infarction (AMI) is a prevalent medical condition associated with significant morbidity and mortality rates. The principal underlying factor leading to myocardial infarction is atherosclerosis, with dyslipidemia being a key risk factor. Nonetheless, relying solely on a single lipid level is insufficient for accurately predicting the onset and progression of AMI. The present investigation aims to assess established clinical indicators in China, to identify practical, precise, and effective tools for predicting AMI. Methods: The study enrolled 267 patients diagnosed with acute myocardial infarction as the experimental group, while the control group consisted of 73 hospitalized patients with normal coronary angiography. The investigators collected general clinical data and relevant laboratory test results and computed the Atherogenic Index of Plasma (AIP) for each participant. Using acute myocardial infarction status as the dependent variable and controlling for confounding factors such as smoking history, fasting plasma glucose (FPG), low-density lipoprotein cholesterol (LDL-C), blood pressure at admission, and diabetes history, the researchers conducted multivariate logistic regression analysis with AIP as an independent variable. Receiver operating characteristic (ROC) curves were employed to determine the predictive value of AIP and AIP combined with LDL-C for acute myocardial infarction. Result: The results of the multivariate logistic regression analysis indicated that the AIP was an independent predictor of acute myocardial infarction. The optimal cut-off value for AIP to predict AMI was -0.06142, with a sensitivity of 81.3%, a specificity of 65.8%, and an area under the curve (AUC) of 0.801 (95% confidence interval [CI]: 0.743-0.859, P < 0.001). When AIP was combined with LDL-C, the best cut-off value for predicting acute myocardial infarction was 0.756107, with a sensitivity of 79%, a specificity of 74%, and an AUC of 0.819 (95% CI: 0.759-0.879, P < 0.001). Conclusions: The AIP is considered an autonomous determinant of risk for AMI. Utilizing the AIP index alone, as well as in conjunction with LDL-C, can serve as effective predictors of AMI.

Clinical significance of carotid intima-media thickness and plasma homocysteine in acute ST-segment elevation myocardial infarction.

Background: Patients with acute ST-segment elevation myocardial infarction (STEMI) often have fewer identifiable traditional risk factors compared to other types of acute coronary syndrome. Therefore, it is necessary to explore more sensitive predictive models different from traditional cardiovascular scoring systems to identify high-risk populations. The retrospective case-control study aimed to investigate the predictive value of carotid intima-media thickness (CIMT) and homocysteine (Hcy) on the occurrence of STEMI. Methods: A total of 198 patients with first STEMI were continuously selected into the observation group, who received emergency coronary angiography in Hefei Hospital Affiliated to Anhui Medical University from January 2020 to January 2022, and a total of 129 patients with chest pain and chest tightness who received coronary angiography to exclude significant coronary artery disease were selected as the control group in the above hospitals during the same period. Hcy was biochemical index determined by fasting blood sampling within 48 h after admission, while CIMT and carotid plaque was measured using ultrasound. Univariate and multivariate logistic regression analysis was used to screen out independent risk factors including Hcy, CIMT and carotid plaque of STEMI. On the basis of traditional risk factors, Hcy, CIMT and carotid plaque were introduced in order to form different combined diagnosis models. The receiver operating characteristic (ROC) curve of single indicator and multi-indicator combined diagnosis were plotted to evaluate the clinical usefulness of the study factors or diagnostic models. Based on those, a Nomogram was constructed to predict STEMI. Results: Hcy (OR =1.161, 95% CI: 1.084-1.244, P<0.001), CIMT (OR =206.968, 95% CI: 22.375-1,914.468, P<0.001), carotid plaque (OR =2.499, 95% CI: 1.214-5.142, P=0.013) were independent risk factors for STEMI (P<0.01). ROC results suggested that the area under the curve (AUC) of Hcy was 0.729, the optimal cut-off value was 13.525 µmol/L. The AUC of CIMT is 0.763, and the optimal cut-off value is 0.875mm. Combined with the independent predictors including smoking, diabetes, high density lipoprotein cholesterol, low density lipoprotein cholesterol, Hcy, CIMT, carotid plaque, the AUC of the diagnosis model was 0.892 (95% CI: 0.856-0.928, P<0.001). Based on the above results, a Nomogram for predicting STEMI was constructed with a C-index of 0.892. The results of the H-L fitting test show that χ2=1.5049, df=2, P=0.4712; the calibration curve of the Nomogram is close to the ideal curve, and the internal validation C-index was 0.880. The clinical decision curve analysis (DCA) shows that the "nomogram line" of the model is far from the "All line" and the "None line". Conclusions: Hcy, CIMT, and carotid artery plaque could be independent risk factors of STEMI. The inclusion of these factors in addition to traditional risk factors can more fully and accurately predict the risk of STEMI. The Nomogram based on the results of this study is feasible and can bring clinical net benefit.

Downregulation of the ubiquitin ligase KBTBD8 prevented epithelial ovarian cancer progression.

OBJECTIVES: Kelch repeat and BTB domain-containing protein 8, KBTBD8, has been identified as a female fertility factor. However, there have been no reports on the role of KBTBD8 in the progression of epithelial ovarian cancer, EOC. Our study aimed to address this issue. METHODS: We first examine KBTBD8 expression in EOC tissues and cells. Next, we performed RNA sequencing to reveal the overall mechanism. Then we investigated the roles of KBTBD8 in the proliferation, migration, and health status of cultured EOC cells. Finally, we employed tumor xenograft models to evaluate the role of KBTBD8 in vivo. RESULTS: First, KBTBD8 level was significantly higher in EOC tissues and cells. Next, comparative RNA sequencing identified more tumorigenesis-related genes that KBTBD8 might regulate. Then we found that KBTBD8 knockdown significantly decreased EOC cell proliferation, migration, and the activities of multiple tumorigenesis-related kinases. Finally, KBTBD8 knockdown significantly diminished ovarian tumor formation in vivo. CONCLUSION: Proper KBTBD8 level is essential for the healthy growth of ovarian somatic cells, such as ovarian epithelial cells. Excessive KBTBD8 might be a significant impetus for EOC progression. KBTBD8 reduction greatly inhibits EOC proliferation and migration.

Extracellular Vesicles (EVs) from Lung Adenocarcinoma Cells Promote Human Umbilical Vein Endothelial Cell (HUVEC) Angiogenesis through Yes Kinase-associated Protein (YAP) Transport.

Yes kinase-associated protein (YAP) plays an important role in angiogenesis and can promote the occurrence and development of many tumor types. However, whether YAP affects tumor angiogenesis in lung cancer, and its potential mechanism in lung cancer, are unknown. In this study, we explored the role of YAP in the angiogenesis of lung adenocarcinoma, and further illustrated its possible mechanism. The expression levels of YAP and the vascular endothelial marker protein CD31 were examined by immunohistochemistry and immunofluorescence in human lung adenocarcinoma tissues, revealing a possible positive correlation between YAP and CD31 in lung adenocarcinoma. The results of the western blotting (WB) of Human Umbilical Vein Endothelial Cells (HUVECs) after coculture with lung adenocarcinoma H1975 cells, H1975 cell-supernatants and H1975-derived EVs showed that YAP derived from H1975 cells can enter HUVECs via EVs. These results were confirmed by immunofluorescence. Finally, we generated H1975 low-YAP expression cells by transfecting the cells with a shYAP lentivirus, and confirmed that the low expression of YAP in H1975 cells inhibits HUVEC angiogenesis by reducing the amount of YAP that enters HUVECs. We found, for the first time, that YAP promotes angiogenesis in lung adenocarcinoma via EVs, at least partially. Our work may provide a promising method for lung cancer treatment by targeting angiogenesis in the future.

Efficient AuPd@GO-based electrochemical nanoprobe for sensitive detection of histone acetylase activity and its inhibitor.

Histone acetylase (HAT p300), which has aroused great concern in fundamental research and clinical applications, serves as one class of significant tumor markers. In our work, a sensitive electrochemical immunoassay for testing HAT p300 based on both graphene-assisted supported AuPd nanomaterial (AuPd@GO composite) and a typical amperometric i-t technique with fast response is developed favorably. The AuPd@GO-based sensing mechanisms are distributed as follows: the HAT p300 derived acetylation reaction occurs at the customized peptide-immobilized electrode; the AuPd@GO composite acts as carrier to immobilize acetyl antibody, thus constructing a sandwich-type electrochemical immunosensor via an antigen and antibody interaction; importantly, a distinct electrochemical signal could be caught due to the AuPd@GO nanomaterial with a favorable electrocatalytic property to the commercialized 3,3,5',5'-tetramethyl benzidine solution (TMB). Taking advantage of AuPd@GO composite, the established immunosensor displays a wide linear range from 1 pM to 1000 nM, and the detection limit is 0.5 pM (S/N = 3) for HAT p300. Next, the biosensor is also used to analyze the inhibitor of HAT p300 successfully, which is promising for promoting the development of electrochemical HAT-related biodetection and drug discovery. Graphical abstract A sensitive electrochemical immunoassay for testing HAT p300 based on both graphene-assisted supported AuPd nanomaterial (AuPd@GO composite) and a typical amperometric i-t technique with fast response is developed favorably.

[Functions of lamin B1 and the new progress of its roles in neurological diseases and tumors].

Lamin B1 is one of the essential members of the nuclear lamina protein family. Its main function is to maintain the integrity of nuclear skeleton, as well as to participate in the cell proliferation and aging by affecting the chromosome distribution. gene expression, and DNA damage repair. The abnormal expression of lamin B1 is related to certain diseases, including neurological diseases [e.g. neural tube defects (NDTs), adult-onset autosomal dominant leukodystrophy (ADLD)] and tumors (e.g. pancreatic cancer). It is also a potential tumor marker as well as drug target. Further research on lamin B1 will help people understand the molecular mechanism of the emergence and development of neural system diseases and tumors, and define a new future in drug target.

Neuropilin-1 (NRP-1) upregulated by IL-6/STAT3 signaling contributes to invasion in pancreatic neuroendocrine neoplasms.

Although the upregulation of Neuropilin-1 (NRP-1) is associated with many solid tumors, its role in pancreatic neuroendocrine neoplasms (pNEN) has not been well elucidated. The aim of this study was to investigate the role of NRP-1 in improving treatment and determining the prognosis of pNEN. In this study, the expression of NRP-1 in pNEN tissue samples and pNEN cell line BON1 was analyzed by Western blot, polymerase chain reaction (PCR) and immunocytochemistry upon exposure to interleukin-6 (IL-6). Additionally, pNEN cell line BON1 was transfected with small interfering RNAs against NRP-1 or signal transducer and activator of transcription 3 (STAT3) and assessed by in vitro invasion assays. The expression of NRP-1 in pNEN tissues was markedly increased compared with adjacent normal pancreatic tissues. High NRP-1 expression was strongly correlated with tumor grades (P = .026), lymph node metastasis (P = .025), and tumor-node-metastasis stages (P = .012). Furthermore, NRP-1 downregulation notably inhibited the metastatic capacity of pNEN cells, and STAT3 knockdown was found to downregulate the expression of NRP-1. BON1 cells upregulated NRP-1 expression upon stimulation with IL-6. This was accompanied by activation/phosphorylation of the AKT and STAT3 signaling pathways. Western blot of extracts of human pNENs confirmed increased NRP-1 expression, as well as AKT/STAT3 phosphorylation in tissue of pNENs with elevated expression levels of IL-6. In conclusion, our findings suggest that NRP-1 is upregulated in pNEN and is correlated with the metastatic capacity of pNEN cells, potentially via interaction with the IL-6/STAT3 signaling pathway.

Autotaxin upregulated by STAT3 activation contributes to invasion in pancreatic neuroendocrine neoplasms.

Although the upregulation of autotaxin (ATX) is associated with many solid tumours, its role in pancreatic neuroendocrine neoplasms (pNEN) has not been well elucidated. The expression of ATX in pNEN tissues and pNEN cell line BON1 was analysed by Western blot, PCR and immunocytochemistry upon exposure to interleukin-6 (IL-6). Additionally, pNEN cell line BON1 was transfected with siRNAs against ATX or signal transducer and activator of transcription 3 (STAT3) and assessed by in vitro invasion assays. The following results were obtained. The expression of ATX in pNEN tissues was significantly increased compared with that in normal pancreatic tissues. High ATX expression was strongly correlated with tumour grade, lymph node metastasis and tumour-node-metastasis stage. Furthermore, ATX downregulation notably inhibited the metastatic capacity of pNEN cells, whereas STAT3 knockdown was found to downregulate the expression of ATX. ATX expression was upregulated in BON1 cells upon stimulation with IL-6, and this was accompanied by activation/phosphorylation of STAT3. Western blot analysis of human pNEN tissue extracts confirmed increased ATX expression and STAT3 phosphorylation with elevated expression levels of IL-6. In conclusion, ATX is upregulated in pNEN and is correlated with the metastatic capacity of pNEN cells, potentially via interaction with STAT3 activation.

Eugenol protects the transplanted heart against ischemia/reperfusion injury in rats by inhibiting the inflammatory response and apoptosis.

The aim of the present study was to investigate the protective effect of eugenol on the transplanted heart and explore its mechanisms of action. Male Sprague-Dawley rats were randomly divided into a sham group (n=10), a eugenol group (n=10 pairs, donors and recipients) and a control group (n=10 pairs, donors and recipients). The recipients in the eugenol group received an intraperitoneal injection of eugenol (20 mg/kg/day). The sham group and the control group received equal volumes of physiological saline by intraperitoneal injection. After 15 days the recipients in the control and eugenol groups underwent abdominal heterotopic heart transplantation, while the sham group received only a coeliotomy. The orthotopic hearts in the sham group and the heterotopic hearts in the eugenol and control groups, as well as the peripheral blood samples from all three groups were taken 3 h post operation for biochemical, histopathological, molecular and apoptosis analyses. Compared with the control group, the eugenol treatment significantly reduced the myocardial malondialdehyde content, serum cardiac troponin I, creatine kinase-MB, tumor necresis factor-α and interleukin-6 levels (P<0.05) and significantly alleviated myocardial injury. Western blot analysis demonstrated that the protein expression of cleaved Poly (ADP-ribose) polymerase 1, BAX and active caspase-3 in the eugenol group were significantly decreased, while B-cell lymphoma 2 expression was significantly increased compared with the control group (P<0.05). The myocardial apoptosis rate of the eugenol group was significantly decreased compared with the control group (P<0.05). In conclusion eugenol treatment significantly reduced myocardial injury and demonstrated protective effects for the transplanted heart.

HE4 expression in lung cancer, a meta-analysis.

BACKGROUND: The prognostic role of Human epididymis protein 4 (HE4) expression in lung cancer remains controversial. We performed this meta-analysis to assess the prognostic value of HE4 expression in lung cancer. METHODS: A systematic literature search was conducted to identify eligible studies in PubMed, Embase and Wanfang databases. The pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to assess the relationship. RESULTS: A total of 1412 patients from 8 studies were included in this meta-analysis. The results of univariate analysis (HR=1.73, 95% CI: 1.19-2.52, P=0.004) and multivariate analysis (HR=2.49, 95% CI: 1.89-3.28, P<0.001) demonstrated that high HE4 expression in lung cancer patients was correlated with poor overall survival (OS). We observed through further stratified analysis of the results of the univariate analysis that high HE4 expression was associated with worse OS in Asian lung cancer patients (HR=2.48, 95% CI: 1.88-3.26, P<0.001). However, there was no significant association between high HE4 expression and poor OS in Caucasian patients (HR=1.12, 95% CI: 0.80-1.55, P=0.513). CONCLUSION: High serum HE4 level was a marker of poor prognosis in lung cancer patients, particularly in Asian patients with lung cancer.

Circulating Tumor Cells Were Associated with the Number of T Lymphocyte Subsets and NK Cells in Peripheral Blood in Advanced Non-Small-Cell Lung Cancer.

In this study, we aim to investigate the correlation between circulating tumor cells (CTCs) and the T lymphocyte subsets and NK cells in peripheral blood in non-small-cell lung cancer (NSCLC). The peripheral blood CTCs were determined by SET-iFISH. Flow cytometry was used to determine the distribution of T lymphocyte subsets and NK cells. Forty-one (49%) patients showed positivity for CTCs. Logistic regression analysis revealed CTC number was negatively correlated with the ratio of CD3+, CD4+, CD4+/CD8+, and NK % in patients at stage IV, while in a positive correlation was noticed between CTC number and regulatory T cell (Tregs) ratio in these patients. Multivariate analysis was performed in combination with the clinical-pathological materials to identify the risk factors for CTC positivity. Differentiation, NSCLC stage, percentages of CD3+CD4+ cells, Tregs, and NK cells were the independent risk factors for CTCs. CTCs were associated with the decrease of immune surveillance in the peripheral blood in NSCLC patients. The decrease of immune surveillance contributed to the escape of CTCs from the killing effects of the immunocytes, as well as the formation of metastasized lesions in the target organs.