Triglyceride-glucose index, renal function and cardiovascular disease: a national cohort study.

BACKGROUND: The triglyceride-glucose (TyG) index is a predictor of cardiovascular diseases; however, to what extent the TyG index is associated with cardiovascular diseases through renal function is unclear. This study aimed to evaluate the complex association of the TyG index and renal function with cardiovascular diseases using a cohort design. METHODS: This study included participants from the China Health and Retirement Longitudinal Study (CHARLS) free of cardiovascular diseases at baseline. We performed adjusted regression analyses and mediation analyses using Cox models. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Renal function was defined by the estimated glomerular filtration rate (eGFR). RESULTS: A total of 6 496 participants were included in this study. The mean age of the participants was 59.6 ± 9.5 years, and 2996 (46.1%) were females. During a maximum follow-up of 7.0 years, 1 996 (30.7%) people developed cardiovascular diseases, including 1 541 (23.7%) cases of heart diseases and 651 (10.0%) cases of stroke. Both the TyG index and eGFR level were significantly associated with cardiovascular diseases. Compared with people with a lower TyG index (median level) and eGFR ≥ 60 ml/minute/1.73 m2, those with a higher TyG index and decreased eGFR had the highest risk of cardiovascular diseases (HR, 1.870; 95% CI 1.131-3.069). Decreased eGFR significantly mediated 29.6% of the associations between the TyG index and cardiovascular diseases. CONCLUSIONS: The combination of a higher TyG index and lower eGFR level was associated with the highest risk of cardiovascular diseases. Renal function could mediate the association between the TyG index and cardiovascular risk.

The Current Developments in Medicinal Plant Genomics Enabled the Diversification of Secondary Metabolites' Biosynthesis.

Medicinal plants produce important substrates for their adaptation and defenses against environmental factors and, at the same time, are used for traditional medicine and industrial additives. Plants have relatively little in the way of secondary metabolites via biosynthesis. Recently, the whole-genome sequencing of medicinal plants and the identification of secondary metabolite production were revolutionized by the rapid development and cheap cost of sequencing technology. Advances in functional genomics, such as transcriptomics, proteomics, and metabolomics, pave the way for discoveries in secondary metabolites and related key genes. The multi-omics approaches can offer tremendous insight into the variety, distribution, and development of biosynthetic gene clusters (BGCs). Although many reviews have reported on the plant and medicinal plant genome, chemistry, and pharmacology, there is no review giving a comprehensive report about the medicinal plant genome and multi-omics approaches to study the biosynthesis pathway of secondary metabolites. Here, we introduce the medicinal plant genome and the application of multi-omics tools for identifying genes related to the biosynthesis pathway of secondary metabolites. Moreover, we explore comparative genomics and polyploidy for gene family analysis in medicinal plants. This study promotes medicinal plant genomics, which contributes to the biosynthesis and screening of plant substrates and plant-based drugs and prompts the research efficiency of traditional medicine.

STAT1/SOCS1/3 Are Involved in the Inflammation-Regulating Effect of GAS6/AXL in Periodontal Ligament Cells Induced by Porphyromonas gingivalis Lipopolysaccharide In Vitro.

Periodontitis involves chronic inflammation of the tissues around the teeth caused by plaque and the corresponding immune response. Growth arrest-specific protein 6 (GAS6) and AXL receptor tyrosine kinase (AXL) are known to be involved in inflammatory diseases, while signal transducer and activator of transcription-1 (STAT1) and suppressor of cytokine signaling (SOCS) are related to inflammatory processes. Moreover, miRNA34a directly targets AXL to regulate the AXL expression. However, the specific roles of GAS6 and AXL in periodontitis remain unclear. This study was designed to explore the effect and mechanism of AXL on the expression of inflammatory cytokines induced by Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS) in human periodontal ligament cells (hPDLCs). The effects of different concentrations of P. gingivalis LPS on the expression of GAS6/AXL in hPDLCs were observed. Additionally, the effect of LPS on AXL was investigated by transfection of the miRNA34a inhibitor. AXL was knocked down or overexpressed to observe the release of inflammatory cytokines interleukin- (IL-) 8 and IL-6. The results showed that the expression levels of GAS6 and AXL decreased after P. gingivalis LPS infection. Transfection of a miR-34a inhibitor to hPDLCs demonstrated a role of miR-34a in the downregulation of AXL expression induced by LPS. Moreover, AXL knockdown or overexpression influencing the expression of IL-8 and IL-6 was investigated under LPS stimulation. AXL knockdown decreased the expression of STAT1 and SOCS1/3. Overall, these results demonstrate that AXL inhibits the expression of LPS-induced inflammatory cytokines in hPDLCs and that STAT1 and SOCS1/3 are involved in the regulation of inflammation by GAS6/AXL.

Salt-induced inhibition of rice seminal root growth is mediated by ethylene-jasmonate interaction.

The phytohormones ethylene and jasmonate play important roles in the adaptation of rice plants to salt stress. However, the molecular interactions between ethylene and jasmonate on rice seminal root growth under salt stress are unknown. In this study, the effects of NaCl on the homeostasis of ethylene and jasmonate, and on rice seminal root growth were investigated. Our results indicate that NaCl treatment promotes ethylene biosynthesis by up-regulating the expression of ethylene biosynthesis genes, whereas NaCl-induced ethylene does not inhibit rice seminal root growth directly, but rather indirectly, by promoting jasmonate biosynthesis. NaCl treatment also promotes jasmonate biosynthesis through an ethylene-independent pathway. Moreover, NaCl-induced jasmonate reduces meristem cell number and cell division activity via down-regulated expression of Oryza sativa PLETHORA (OsPLT) and cell division-related genes, respectively. Additionally, NaCl-induced jasmonate inhibits seminal root cell elongation by down-regulating the expression of cell elongation-related genes. Overall, salt stress promotes jasmonate biosynthesis through ethylene-dependent and -independent pathways in rice seminal roots, and jasmonate inhibits rice seminal root growth by inhibiting root meristem cell proliferation and root cell elongation.

Potential Suppressive Effect of Nicotine on the Inflammatory Response in Oral Epithelial Cells: An In Vitro Study.

Smoking is a well-recognized risk factor for oral mucosal and periodontal diseases. Nicotine is an important component of cigarette smoke. This study aims to investigate the impact of nicotine on the viability and inflammatory mediator production of an oral epithelial cell line in the presence of various inflammatory stimuli. Oral epithelial HSC-2 cells were challenged with nicotine (10-8-10-2 M) for 24 h in the presence or absence of Porphyromonas gingivalis lipopolysaccharide (LPS, 1 µg/mL) or tumor necrosis factor (TNF)-α (10-7 M) for 24 h. The cell proliferation/viability was determined by MTT assay. Gene expression of interleukin (IL)-8, intercellular adhesion molecule (ICAM)-1, and ß-defensin was assayed by qPCR. The production of IL-8 protein and cell surface expression of ICAM-1 was assessed by ELISA and flow cytometry, respectively. Proliferation/viability of HSC-2 cells was unaffected by nicotine at concentrations up to 10-3 M and inhibited at 10-2 M. Nicotine had no significant effect on the basal expression of IL-8, ICAM-1, and ß-defensin. At the same time, it significantly diminished P. gingivalis LPS or the TNF-α-induced expression levels of these factors. Within the limitations of this study, the first evidence was provided in vitro that nicotine probably exerts a suppressive effect on the production of inflammatory mediators and antimicrobial peptides in human oral epithelial cells.

Crosstalk between Akt and NF-κB pathway mediates inhibitory effect of gas6 on monocytes-endothelial cells interactions stimulated by P. gingivalis-LPS.

Correlation between periodontitis and atherosclerosis is well established, and the inherent mechanisms responsible for this relationship remain unclear. The biological function of growth arrest-specific 6 (gas6) has been discovered in both atherosclerosis and inflammation. Inhibitory effects of gas6 on the expression of inflammatory factors in human umbilical vein endothelial cells (HUVECs) stimulated by Porphyromonas gingivalis lipopolysaccharide (P. gingivalis-LPS) were reported in our previous research. Herein, the effects of gas6 on monocytes-endothelial cells interactions in vitro and their probable mechanisms were further investigated. Gas6 protein in HUVECs was knocked down with siRNA or overexpressed with plasmids. Transwell inserts and co-culturing system were introduced to observe chemotaxis and adhering affinity between monocytes and endothelial cells in vitro. Expression of gas6 was decreased in inflammatory periodontal tissues and HUVECs challenged with P. gingivalis-LPS. The inhibitory effect of gas6 on chemotaxis and adhesion affinity between monocytes and endothelial cells was observed, and gas6 promoted Akt phosphorylation and inhibited NF-κB phosphorylation. To our best knowledge, we are first to report that gas6 inhibit monocytes-endothelial cells interactions in vitro induced by P. gingivalis-LPS via Akt/NF-κB pathway. Additionally, inflammation-mediated inhibition of gas6 expression is through LncRNA GAS6-AS2, rather than GAS6-AS1, which is also newly reported.

MicroRNA-183 affects the development of gastric cancer by regulating autophagy via MALAT1-miR-183-SIRT1 axis and PI3K/AKT/mTOR signals.

Gastric cancer (GC) remains to be a familiar malignant tumor with poor prognosis and daunting impacts on global health. We planned to grab the latent impacts of microRNA-183 in regulating cell autophagy, thus to clarify its possible regulatory principle in GC. The miR-183 level in GC tissues and cell lines was investigated. The impacts of miR-183 dysregulation on cell biological performances including viability, apoptosis and autophagy of GC cell lines including SGC-7901 were detected. Also, cells were disposed with 3-methyladenine (3-MA, an autophagy inhibition) before dysregulation of miR-183 to further investigate the correlation between cell autophagy and viability or apoptosis. Furthermore, the regulatory mechanisms between miR-183 and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), silent mating type information regulation 1 (SIRT1) or PI3K/AKT/mTOR pathway were explored. miR-183 was under-expressed both in GC tissues and in cell lines. miR-183 mimic alone depressed SGC-7901 cell viability and enhanced cell apoptosis and autophagy, whereas miR-183 inhibitor exhibited opposite effects. Moreover, the impacts of miR-183 on SGC-7901 cell viability and apoptosis were mediated by affecting the activation of autophagy. Our results indicate that miR-183 is under-expressed in GC cells and depression of miR-183 may enhance GC cell viability and inhibit cell apoptosis by affecting the activation of cell autophagy. MALAT1-miR-183-SIRT1 axis and PI3K/AKT/mTOR pathway may be mechanisms to mediate autophagy in GC. miR-183 may serve as a towardly therapeutic target for GC.

High expression of TCF12 contributes to gastric cancer development via being target regulated by miR-183 and activating PI3K/AKT pathway.

This study aimed to explore the role of transcription factor 12 (TCF12) in the process of gastric cancer (GC) and to elucidate its possible regulatory mechanism. The expression data of GC tissues and matched normal tissues were downloaded from The Cancer Genome Atlas (TCGA) database. Survival analysis for GC patients with different levels of TCF12 was performed by the Kaplan-Meier analysis. In addition, TCF12 was suppressed in human GC cell lines AGS and MKN-45, followed by detecting cell biological processes (proliferation, apoptosis, migration, and invasion). Moreover, the association between TCF12 and the phosphatidylinositol 3-kinase (PI3K)/AKT signal was elucidated. Besides, the potential micro RNAs that could target TCF12 expression were explored. The results showed that TCF12 was highly expressed in GC tissues and TCF12 upregulation was associated with poor prognosis of GC patients. In addition, suppression of TCF12 significantly inhibited the proliferation, migration, and invasion of both AGS and MKN45 cells, as well as induced apoptosis of the two cell lines. Moreover, suppression of TCF12 significantly decreased the expression of p-AKT, cyclin D1, p-P70, and ß-catenin in both AGS and MKN45 cells. Besides, TCF12 was target regulated by miR-183 in GC cells. Our findings reveal that TCF12 is upregulated in GC and its upregulation is associated with poor prognosis of GC patients. To sum up, downregulation of TCF12 may inhibit GC development via being target regulated by miR-183 and inhibiting the PI3K/AKT signal. TCF12 may function as a potential therapeutic target for GC.

Size-matching hierarchical micropillar arrays for detecting circulating tumor cells in breast cancer patients' whole blood.

Circulating tumor cells (CTCs) are important markers for cancer diagnosis and treatment, but it is still a challenge to recognize and isolate CTCs because they are very rare in the blood. To selectively recognize CTCs and improve the capture efficiency, micro/nanostructured substrates have been fabricated for this application; however the size of CTCs is often ignored in designing and engineering micro/nanostructured substrates. Herein, a spiky polymer micropillar array is fabricated for capturing CTCs with high efficiency. The surface of the micropillar is cactus-like, and is composed of nanospikes. This hierarchical polymer array is designed according to the size of CTCs, which allows for more interactions of the CTCs with the array by setting the size of gaps among the micropillars to match with the CTCs. This polymer array is created by molding on an ordered silicon array, and then it is coated with an antiepithelial cell adhesion molecule antibody (anti-EpCAM). After co-culture with MCF-7 cells for 45 min, the capture efficiency of this array for CTCs is up to 91% ± 2%. Moreover, the anti-EpCAM modified polymer micropillar arrays present an excellent capacity to isolate CTCs from the whole blood samples of breast cancer patients. This study may provide a new concept for capturing target cells by designing and engineering micro/nanostructured substrates according to the size of target cells.

Dysregulation of long non-coding RNA SNHG12 alters the viability, apoptosis, and autophagy of prostate cancer cells by regulating miR-195/CCNE1 axis.

This study aimed to explore the role and mechanism of lncRNA small nucleolar RNA host gene 12 (SNHG12) in the development of prostate cancer (PCa). The expression of SNHG12 in the serum of PCa patients as well as PCa cells was determined, and then we investigated whether SNHG12 could act as a competing endogenous RNA (ceRNA) to mediate the development of PCa. Furthermore, the association between SNHG12 and activation of the PI3K/AKT/mTOR pathway was explored. SNHG12 expression was up-regulated in the serum of PCa patients as well as PCa cells. High expression of SNHG12 resulted in a poor prognosis of PCa patients. Moreover, suppression of SNHG12 inhibited viability and promoted apoptosis and autophagy of LNCaP cells. Furthermore, SNHG12 was found to act as a ceRNA to regulate the expression of Cyclin E1 (CCNE1) by sponging miR-195. Lastly, suppression of SNHG12 inhibited the activation of PI3K/AKT/mTOR pathway. Our results revealed that up-regulation of SNHG12 promoted the viability and inhibited apoptosis and autophagy of PCa cells by regulating CCNE1 expression by sponging miR-195. Moreover, activation of PI3K/AKT/mTOR pathway is a key downstream mechanism regulating SNHG12-mediated the development of PCa. Our findings provide an experimental basis for targeted therapy of PCa.

Long noncoding RNA PDIA3P promotes breast cancer development by regulating miR-183/ITGB1/FAK/PI3K/AKT/ß-catenin signals.

Aberrantly expressed long noncoding RNAs (lncRNAs) play crucial roles in the process of breast cancer (BC). This research aims to dig the possible roles and regulatory mechanism of lncRNA protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P1) in BC. The mRNA level of PDIA3P both in BC tissues and in cells were determined, followed by the investigation of the effects of PDIA3P suppression on cell biological processes including the viability, apoptosis, migration and invasion. Furthermore, whether PDIA3P modulated the expression of integrin ß1 (ITGB1) expression by competitively sponging miR-183 and then regulated the activation of FAK/PI3K/AKT/ß-catenin pathway was explored. PDIA3P was discovered as up-regulated in BC tissues and cells. PDIA3P suppression markedly decreased cell viability, promoted apoptosis, and inhibited migration and invasion in MCF-7 cells. In addition, PDIA3P was found to be negatively interacting with miR-183, and PDIA3P regulated tumor growth and metastasis through negatively regulating miR-183. Moreover, ITGB1 was targeted by miR-183 and involved in tumor growth and metastasis. Lastly, PDIA3P suppression markedly inhibited the activation of FAK/PI3K/AKT/ß-catenin pathway, which was significantly reversed after simultaneous inhibition of miR-183. Our results reveal that PDIA3P may forpromote BC development by sponging miR-183 to regulate ITGB1, thus inducing the activation of FAK/PI3K/AKT/ß-catenin signals. PDIA3P may serve as a promising biomarker or target for the detection or treatment of BC.