Corrigendum: Atherogenic index of plasma and coronary artery disease in the adult population: A meta-analysis.

[This corrects the article DOI: 10.3389/fcvm.2021.817441.].

Triglyceride-glucose index and the incidence of atherosclerotic cardiovascular diseases: a meta-analysis of cohort studies.

BACKGROUND: Insulin resistance has been demonstrated to be involved in the pathogenesis of atherosclerotic cardiovascular diseases (ASCVDs). This study evaluated the association between the triglyceride-glucose (TyG) index, a novel surrogate indicator of insulin resistance, and the incidence of ASCVDs in people without ASCVDs at baseline by performing a meta-analysis. METHODS: Cohort studies reporting the multivariate-adjusted association between the TyG index and the incidence of ASCVDs were obtained by searching the PubMed and Embase databases. A random-effects model incorporating intra-study heterogeneity was applied to combine the results. RESULTS: Eight cohort studies comprising 5,731,294 participants were included in this meta-analysis. The results showed that compared to those with the lowest TyG index category, participants with the highest TyG index category were independently associated with a higher risk of ASCVDs [hazard ratio (HR): 1.61, 95% confidence interval (CI) 1.29-2.01, I2 = 80%, P < 0.001]. This finding was consistent with the meta-analysis results with the TyG index analyzed as a continuous variable (HR per 1-unit increment of the TyG index: 1.39, 95% CI 1.18-1.64, I2 = 89%, P < 0.001). Subgroup analyses suggested that the age, sex, and diabetic status did not significantly affect the association (for subgroup analyses, all P > 0.05). Moreover, participants with the highest TyG index category were independently associated with a higher risk of coronary artery disease [(CAD), HR: 1.95, 95% CI 1.47-2.58, I2 = 92%, P < 0.001] and stroke (HR: 1.26, 95% CI 1.23-1.29, I2 = 0%, P < 0.001). CONCLUSIONS: A higher TyG index may be independently associated with a higher incidence of ASCVDs, CAD, and stroke in people without ASCVDs at baseline.

Sporadic multiple renal angiomyolipoma with lymph node involvement: a case report and literature review.

Angiomyolipoma (AML) is a benign tumor that mainly occurs in the kidneys. Simultaneous involvement of the kidney and local regional lymph nodes is very rare and might be misdiagnosed as a metastasizing malignant cancer. In the present study, a 50-year-old woman was referred to our hospital after a routine health screening ultrasound. Sporadic multiple renal AML with lymph node involvement was suspected based on the clinical manifestations and radiologic features. Partial nephrectomy was performed and a para-inferior vena cava lymph node was removed. The pathologic results confirmed multiple AML with lymph node invasion. We also reviewed the English-language literature regarding renal AML with lymph node involvement. We found that middle-aged women were likely to develop this disease and that loin pain was the main presenting feature. Most patients had no history of tuberous sclerosis complex. Radical nephrectomy was the predominant treatment. No local recurrence or distant metastasis occurred in any patients after radical nephrectomy or partial nephrectomy. In conclusion, renal AML with lymph node involvement is rare but can occur in both patients with tuberous sclerosis complex and those with multiple sporadic AML. Partial nephrectomy should be the first-line treatment, after which further treatment is not necessary.

Atherogenic Index of Plasma and Coronary Artery Disease in the Adult Population: A Meta-Analysis.

Background: The atherogenic index of plasma (AIP), which is the logarithm of the ratio between the triglyceride and high-density lipoprotein cholesterol (TG/HDL-C) concentrations in molar units, is correlated with the burden of atherosclerosis. This study aimed to evaluate the association between the AIP and coronary artery disease (CAD) in the adult population by performing a meta-analysis. Methods: Observational studies relevant for this meta-analysis were identified by searching the PubMed, Embase, and Web of Science databases. Only studies using multivariate analysis were considered. A random-effects model, which incorporates potential intra-study heterogeneity, was applied to combine the results. Results: Ten observational studies were included. In studies with the AIP analyzed as a continuous variable, a higher AIP was associated with a higher odds of CAD (adjusted risk ratio [RR] per 1-standard deviation [SD] increment of AIP: 2.10, 95% confidence interval [CI]: 1.51-2.93, P < 0.001, I2 = 90%). Further analysis of studies with the AIP analyzed as a categorical variable showed a higher odds of CAD (adjusted RR: 2.35, 95% CI: 1.88-2.93, P < 0.001, I2 = 37%) in the participants with the highest versus the lowest AIP value. Subgroup analyses demonstrated consistent results in asymptomatic and symptomatic populations as well as in male and female participants (all between-group P values > 0.05). Discussion: Current evidence, mostly from cross-sectional studies, suggests that a higher AIP value may be independently associated with CAD in the adult population.

LIPH promotes metastasis by enriching stem-like cells in triple-negative breast cancer.

Lipase member H (LIPH), a novel member of the triglyceride lipase family. The clinical implications of its expression in breast cancer are still unclear. Therefore, in this study, we investigated the associations between LIPH and the tumorigenic behaviours of 144 triple-negative breast cancer (TNBC) patients. The ratio and mammosphere-forming ability of CD44+/CD24- stem-like cells were tested. The role of LIPH in breast cancer cell migration and invasion was also evaluated. In addition, the effect of LIPH silencing on mitochondrial respiration was determined using the Seahorse assay. Finally, the effect of LIPH silencing on protein expression was determined via tandem mass tag-based spectrometry and Western blotting. We found that LIPH expression was associated with metastasis in lymph nodes and distant organs (P = 0.025), resulting in poor survival among breast cancer patients (P = 0.027). LIPH knockdown significantly decreased both the ratio of CD44+ /CD24- stem-like cells and their mammosphere-forming ability. LIPH silencing promoted apoptosis, arrested cell cycle in the G2/M phase, mitigated the oxidation-related oxygen consumption rate in the mitochondria, and reduced metabolism. LIPH inhibited adhesion between tumour cells and enhanced the epithelial-mesenchymal transition. Tandem mass spectrometric analysis presented 68 proteins were differentially expressed in LIPH-silenced cells and LIPH-mediated modulation of tumour cell adhesion depended on integrin-related CAPN2 and paxillin signalling. Overall, our findings provided strong evidence that LIPH up-regulation promoted metastasis and the stemness of TNBC cells. Therefore, targeting LIPH is a potentially viable strategy for preventing metastasis in TNBC.

Knockdown of endothelin receptor B inhibits the progression of triple-negative breast cancer.

Endothelin receptor B (EDNRB) is one of the receptors in the endothelin axis and its upregulated expression is associated with tumorigenesis and metastasis of several types of solid tumors. However, the expression profile of EDNRB in breast cancer and its role in the progression of breast cancer are unclear. Here, we show that EDNRB expression is higher in metastatic tumors than in primary breast cancer, and is associated significantly with lymph node metastasis and poor survival in Chinese patients with breast cancer. EDNRB expression was particularly upregulated in triple-negative breast cancer (TNBC) cells. Moreover, EDNRB silencing by a specific shRNA significantly attenuated the proliferation, migration, and invasiveness of MDA-MB-231 and BT549 cells and increased their apoptosis, as well as retarded the growth of implanted tumors in mice. Tandem mass spectrometry analysis indicated that 248 proteins were differentially expressed in EDNRB-silenced cells and their cellular organelles, and these proteins participate in many processes. EDNRB silencing decreased protein kinase B and extracellular regulated protein kinase phosphorylation and promoted the mesenchymal-to-epithelial transition process in MDA-MB-231 cells. Therefore, our findings provide strong evidence for the first time that knockdown of EDNRB expression inhibits the progression of TNBC and that EDNRB can serve as a prognostic biomarker and therapeutic target for the treatment of TNBC.

Circulating CD14+CD163+CD115+ M2 monocytes are associated with the severity of new onset severe acute pancreatitis in Chinese patients.

BACKGROUND: Despite the role of monocytes in the pathogenesis of severe acute pancreatitis (SAP), it remains unclear how different subtypes of monocytes regulate and contribute to this pathogenesis. METHODS: We examined the numbers of different subsets of monocytes by flow cytometry in 21 SAP, 15 mild acute pancreatitis (MAP) and 13 healthy controls (HC). The concentrations of plasma cytokines were assessed by cytometric bead array. Disease severity was evaluated based on the acute physiology and chronic health evaluation (APACHE) II score and plasma C-reactive proteins (CRP) levels. RESULTS: Compared with the numbers in MAP patients and HC, we observed that the numbers of CD14+CD163-, CD14+CD163-MAC387+, CD14+CD163-IL-12+ M1 monocytes, and CD115+, CD204+, IL-10+ M2 monocytes were significantly increased in SAP patients. In addition, these patients showed higher plasma levels of interleukin (IL)-12 and IL-10. Furthermore, the number of CD14+CD163-, CD14+CD163-MAC387+ M1 monocytes and the plasma IL-12 concentration showed a positive association with the CRP level, while the number of CD204+, IL-10+ M2 monocytes and the plasma IL-10 concentration showed a positive correlation with the APACHE II score. Importantly, the CD115+ M2 subset displayed a positive correlation with both the CRP level and APACHE II score, and treatment of SAP significantly reduced the number of this subset. CONCLUSIONS: The CD14+CD163+CD115+ M2 monocyte count appears to be important factor in determining the severity and prognosis of SAP. Both the pro- and anti-inflammatory monocytes appear to participate in the pathogenesis of SAP.

Epigenetic suppression of the antitumor cytotoxicity of NK cells by histone deacetylase inhibitor valproic acid.

Natural killer (NK) cells play an essential role in the fight against tumor development. The therapeutic use of autologous NK cells has been exploited to treat human malignancies, yet only limited antitumor activity is observed in cancer patients. In this study, we sought to augment the antitumor activity of NK cells using epigenetic approaches. Four small molecules that have been known to promote epigenetic reprogramming were tested for their ability to enhance the activity of NK cells. Using a tumor cell lysis assay, we found that the DNA demethylating agent 5-azacytidine and vitamin C did not significantly affect the tumor killing ability of NK cells. The thyroid hormone triiodothyronine (T3) slightly increased the activity of NK cells. The histone deacetylase inhibitor valproic acid (VPA), however, inhibited NK cell lytic activity against leukemic cells in a dose-dependent manner. Pretreatment using VPA reduced IFNγ secretion, impaired CD107a degranulation, and induced apoptosis by activating the PD-1/PD-L1 pathway. VPA downregulated the expression of the activating receptor NKG2D (natural-killer group 2, member D) by inducing histone K9 hypermethylation and DNA methylation in the gene promoter. Histone deacetylase inhibitors have been developed as anticancer agents for use as monotherapies or in combination with other anticancer therapies. Our data suggest that the activity of histone deacetylase inhibitors on NK cell activity should be considered in drug development.

Expression analysis of apolipoprotein E and its associated genes in gastric cancer.

Gastric cancer is a common type of cancer worldwide, and has a poor prognosis, in part due to the low rates of early diagnosis and the limited treatment methods available. Apolipoprotein E (ApoE) is involved in exogenous cholesterol transport and may be important in enabling tumor cells to fulfill their high cholesterol requirements. A number of reports have indicated that ApoE affects the development and prognosis of gastric cancer. Therefore, the aim of the present study was to investigate the genes and transcription factors that interact with ApoE during the development of gastric cancer. Using gene expression profiling, the BioGRID database and the transcriptional regulatory element database, gene expression and regulatory networks in gastric cancer tissues and adjacent normal tissues were analyzed. The data demonstrated that eight genes associated with ApoE were differentially expressed, with six of these upregulated and two downregulated. Functionally, these genes were involved in the JAK-STAT cascade, acute-phase response, acute inflammatory response, and the steroid hormone response. Among these ApoE-associated genes, expression of the signal transducer and activator of transcription 2 (STAT2) and STAT3 transcription factors was upregulated. To the best of our knowledge, this is the first study to demonstrate the network of ApoE-related genes and transcription factors in gastric cancer. Additional studies are required in order to confirm these data and to translate the results into the identification of clinical biomarkers and novel treatment strategies for gastric cancer.

MicroRNA-1 down-regulates proliferation and migration of breast cancer stem cells by inhibiting the Wnt/ß-catenin pathway.

We investigated the miRNA profiles of breast cancer stem cells (CSCs) and non-CSC tumor cells by miRNA microarray and determined the effect of altered miR-1 expression on proliferation and migration of breast CSCs. The potential targets of miR-1 in the Wnt/ß-catenin signaling were characterized by bioinformatics analysis and luciferase assay. We found that 14 miRNAs were up-regulated and 13 were down-regulated in the ESA+CD44+CD24-lineage- CSCs, related to ESA+CD44-CD24+lineage- non-CSC tumor cells. The miR-1 expression was associated inversely with aggressiveness of breast cancers. Furthermore, enhanced miR-1 expression decreased the percentages of SKBR3/CSCs and miR-1 inhibition increased the percentages of MCF-7/CSCs. Enhanced miR-1 expression significantly reduced the Frizzled 7 and Tankyrase-2 (TNKS2)-regulated luciferase activity in 293T cells and decreased Frizzled 7, TNKS2, c-Myc, octamer-binding transcription factor 4 (Oct4) and Nanog expression and the ratios of nuclear to cytoplasmic ß-catenin as well as ß-catenin-dependent luciferase activity in breast CSCs in vitro. miR-1 inhibited proliferation, migration and wound healing of breast CSCs in vitro. Enhanced miR-1 expression inhibited the growth of implanted MCF-7/CSCs while miR-1 inhibition promoted the growth of implanted MCF-7/CSCs in vivo. Our data indicate that miR-1 down-regulates breast CSC stemness, proliferation and migration by targeting the Frizzled 7 and TNKS2 to inhibit the Wnt/ß-catenin signaling.

Lipase member H is a novel secreted protein associated with a poor prognosis for breast cancer patients.

The objective of this study is to identify the expression status and clinical implications of lipase member H (LIPH) in breast cancer in order to develop strategies for breast cancer management. LIPH expression status was detected in 346 breast cancer specimens by immunohistochemistry. The relationship between LIPH expression, clinico-pathological parameters, and prognosis of breast cancer was determined. LIPH expression was higher in breast cancer specimens than in paracarcinoma tissues (P=0.01). In total, 64.74% (224/346) of breast cancer samples had high expression of the LIPH protein. LIPH was related to tumor size, histological grade, lymph node metastasis, and distant metastasis (P=0.073, 0.001, 0.001, and 0.001, respectively). Furthermore, individuals with high LIPH expression had a significantly higher rate of distant metastasis and poorer disease-specific survival than those with no or low LIPH expression (P=0.01). A Cox regression test indicated that the LIPH protein was an independent prognostic factor (P=0.001). LIPH was differentially expressed in breast cancer individuals and is an independent prognostic factor for breast cancer as well as a potential target for its management.