Association of the triglyceride-glucose index and its related parameters with frailty.

BACKGROUND: Frailty is a dynamic geriatric condition. Limited studies have examined the association of the triglyceride-glucose (TyG) index and its related indicators [TyG index, triglyceride glucose-waist to height ratio (TyG-WHtR), triglyceride glucose-waist circumference (TyG-WC), and triglyceride glucose-body mass index (TyG-BMI)] with frailty, and the potential links among them remain unclear. On the basis of data from the National Health and Nutrition Examination Survey (NHANES), this study investigated the potential relationships of the TyG index and its related indices with frailty. METHODS: This research included 7,965 participants from NHANES 2003-2018. The relationship of the TyG index and its related indices with frailty was investigated with binary logistic regression analyses, restricted cubic spline (RCS), and receiver operating characteristic (ROC) curve. Potential influences were further investigated through stratified analyses and interaction tests. RESULTS: The prevalence of frailty in the participants of this study was 25.59%, with a average frailty index of 0.16 (0.00). In the three regression analysis models, the continuous TyG index and its associated indices were positively associated with frailty. In addition, quartiles of TyG, TyG-WC, TyG-WHtR, and TyG-BMI were significantly associated with increased frailty prevalence in the fully adjusted models (TyG Q4 vs. Q1, OR = 1.58, 95% CI: 1.19, 2.09, P = 0.002; TyG-WC Q4 vs. Q1, OR = 2.40, 95% CI: 1.90, 3.04, P < 0.001; TyG-WHtR Q4 vs. Q1, OR = 2.26, 95% CI: 1.82, 2.81, P < 0.001; TyG- BMI Q4 vs. Q1, OR = 2.16, 95% CI: 1.76, 2.64, P < 0.001). According to RCS analysis, TyG, TyG-WC, TyG-WHtR, and TyG-BMI were linearly and positively associated with frailty. ROC curves revealed that TyG-WHtR (AUC: 0.654) had greater diagnostic value for frailty than TyG (AUC: 0.604), TyG-BMI (AUC: 0.621), and TyG-WC (AUC: 0.629). All of the stratified analyses and interaction tests showed similar results. CONCLUSIONS: Elevated TyG and its associaed indices are associated with an increased prevalence of frailty. Reasonable control of blood glucose and blood lipids, and avoidance of obesity, may aid in reducing the occurrence of frailty in middle-aged and older adults.

Low ankle-brachial index is associated with higher cardiovascular mortality in individuals with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Ankle brachial index (ABI) is a risk factor for cardiovascular mortality, but it is unclear whether ABI is associated with cardiovascular mortality in patients with nonalcoholic fatty liver disease (NAFLD). The current study aimed to evaluate the association between ABI with cardiovascular and all-cause mortality in patients with NAFLD. METHODS: We performed a cohort study using the data of the1999-2004 National Health and Nutrition Examination Survey data of adults. Mortality data were followed up to December 2015. NAFLD was defined by the hepatic steatosis index or the US fatty liver index. ABI was classified into three groups: ABI ≤ 0.9 (low value); 0.9 < ABI ≤ 1.1 (borderline value); ABI greater than 1.1 (normal value). RESULTS: We found that low ABI was associated with an increased risk of cardiovascular mortality in patients with NAFLD (HR: 2.42, 95% CI 1.10-5.33 for low value ABI vs normal value ABI, P for trend = 0.04), and the relationship was linearly and negatively correlated in the range of ABI < 1.4. However, low ABI was not associated with all-cause mortality in patients with NAFLD. Stratified by cardiovascular disease, ABI remains inversely correlated with cardiovascular mortality in NAFLD patients without cardiovascular disease. Stratified by diabetes, ABI is inversely correlated with cardiovascular mortality in NAFLD patients regardless of diabetes status. CONCLUSIONS: Low ABI is independently associated with higher cardiovascular mortality in NAFLD cases. This correlation remains significant even in the absence of pre-existing cardiovascular disease or diabetes.

Alpha-fetoprotein upregulates hepatocellular carcinoma cell-intrinsic PD-1 expression through the LATS2/YAP/TEAD1 pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) cell-intrinsic programmed death 1 (PD-1) promotes tumor progression. However, the mechanisms that regulate its expression are unclear. This study investigated the impact of alpha-fetoprotein (AFP) on HCC cell-intrinsic PD-1 expression. METHODS: The expression of PD-1 and AFP at the gene and protein levels was detected using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB). Proteins interacting with AFP were examined by co-immunoprecipitation (CO-IP). Chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays were used to identify transcription-enhanced association domain 1 (TEAD1) binding to the promoter of PD-1. RESULTS: The expression of HCC cell-intrinsic PD-1 was positively correlated with AFP. Mechanistically, AFP inhibited the phosphorylation of large tumor suppressor 2 (LATS2) and yes-associated protein (YAP). As a result, YAP is transferred to the nucleus and forms a transcriptional complex with TEAD1, promoting PD-1 transcription by binding to its promoter. CONCLUSION: AFP is an upstream regulator of the HCC cell-intrinsic PD-1 and increases PD-1 expression via the LATS2/YAP/TEAD1 axis. GENERAL: Our findings provide insight into the mechanisms of HCC development and offer new ideas for further in-depth studies of HCC.

Licoricidin combats gastric cancer by targeting the ICMT/Ras pathway in vitro and in vivo.

Licoricidin, a type of isoflavonoid, is extracted from the root of Glycyrrhiza glabra. It has been widely proven that licoricidin possesses multiple biological activities, including anti-cancer effects and a powerful antimicrobial effect against Helicobacter pylori (H. pylori). However, the exact mechanism of licoricidin against gastric cancer remains unclear. In this study, we comprehensively explored the effects of licoricidin on MGC-803 gastric cancer cells in vitro and in vivo and further elucidated its mechanism of action. Our results revealed that licoricidin exhibited multiple anti-gastric cancer activities, including suppressing proliferation, inducing apoptosis, arresting the cell cycle in G0/G1 phase, and inhibiting the migration and invasion abilities of MGC-803 gastric cancer cells. In addition to this, a total of 5861 proteins were identified by quantitative proteomics research strategy of TMT labeling, of which 19 differential proteins (two upregulated and 17 downregulated) were screened out. Combining bioinformatics analyses and the reported roles in cancer progression of the 19 proteins, we speculated that isoprenyl carboxyl methyltransferase (ICMT) was the most likely target of licoricidin. Western blot assays and IHC assays subsequently proved that licoricidin significantly downregulated the expression of ICMT, both in MGC-803 cells and in xenograft tumors. Moreover, licoricidin effectively reduced the level of active Ras-GTP and blocked the phosphorylation of Raf and Erk, which may be involved in its anti-gastric cancer effects. In summary, we first demonstrated that licoricidin exerted favorable anti-gastric cancer activities via the ICMT/Ras pathway, which suggests that licoricidin, as a natural product, could be a novel candidate for the management of gastric cancer.

Association Between Hemoglobin Levels and Osteoporosis in Chinese Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study.

Purpose: To explore the relationship between hemoglobin levels and osteoporosis and the risk factors for osteoporosis in patients with type 2 diabetes mellitus (T2DM). Patients and methods: A cross-sectional study was conducted in 495 T2DM adults. Medical data were collected from electronic medical records. Results: T2DM patients with osteoporosis had significant lower hemoglobin levels (P < 0.001). Spearman correlation analysis and logistic regression analysis showed that age, female, body mass index (BMI), smoking, drinking and hemoglobin levels were significantly associated with osteoporosis in T2DM patients (all P < 0.05). After adjustment for BMI, diabetic duration, estimated glomerular filtration rate (eGFR), smoking and drinking, a significant association between hemoglobin levels and osteoporosis was observed in T2DM males aged 50 years and older (odds ratio [OR] = 0.978, 95% confidence interval [CI]: 0.958-0.998, P = 0.030). Compared to Q3 groups with normal hemoglobin levels, Q1 groups with anemia had an odd of osteoporosis increased 2.9-fold in T2DM men after adjustment for age, BMI, diabetic duration, eGFR, smoking and drinking (P = 0.032). Conclusion: Hemoglobin levels were associated with the presence of osteoporosis in T2DM men, especially in those aged 50 years and older.

Long non-coding RNA TNK2 AS1/microRNA-125a-5p axis promotes tumor growth and modulated phosphatidylinositol 3 kinase/AKT pathway.

BACKGROUND AND AIM: Long non-coding RNA (lncRNA) TNK2 AS1 is a noncoding RNA with the capability of affecting microRNAs (miRNAs) levels and gene expression. The study was designed to investigate the mechanism of TNK2 AS1 in gastric cancer. METHODS: The loss and gain of function of TNK2 AS1 were investigated by analyzing the malignant behavior of AGS cells including the abilities of migration, invasion, and epithelial-mesenchymal transition (EMT) process via wound healing and transwell assay, as well as western blot. The targeting relationship of LncRNA TNK2 AS1 was analyzed through searching bioinformatics database, luciferase reporter assay, and RNA immunoprecipitation (RIP) assay. Tumor-bearing experiment in nude mice was performed to further confirm the regulatory role of TNK2 AS1 in vivo. Immunofluorescence assay for Ki67 expression was carried out in tumor tissues of mice model. RESULTS: The results showed that TNK2 AS1 overexpression promoted the malignant behaviors of AGS cells, which could be weakened by miR-125a-5p mimic addition. In addition, Jumonji, At-rich interaction domain (JARID2), and phosphatidylinositol 3 kinase (PI3K)/AKT pathway were regulated by TNK2-AS1/miR-125a-5p axis. In vivo, TNK2 AS1/miR-125a-5p axis promoted tumor growth and led to increases in green fluorescence intensity and vimentin expression and a decrease in E-cadherin level, which could be mediated by JARID2 and PI3K/AKT pathway. CONCLUSION: Therefore, a conclusion was drawn that TNK2-AS1/miR-125a-5p promoted the progression of gastric cancer.