The interest focusing on Eriobotrya japonica leaf triterpene acid (ELTA) has increased recently because of its beneficial effects on health. However, there has been a lack of experimental data on its toxicity. The present study therefore was conducted to evaluate its toxicity in ICR mice. The results showed that ELTA produced neither mortality nor toxicity of the main organs in ICR male and female mice in both acute (0.30, 0.65, 1.39, and 3.00 g·kg −1 body weight) and subacute (150, 300, and 600 mg·kg −1 BW) 28-day toxicity studies. Because of lacking apparently adverse effects found in the hematology, clinical biochemistry, and histopathology evaluation, results of the present study together with the beneficial effects make ELTA as a promising dietary supplement and indicated that ELTA administered orally might have a large safety margin for human.
Abstract Enhanced glycolysis has been identified as a hallmark of cancer. As a novel oncogene, ACTL6A is aberrantly amplified in several types of human cancers and has been shown to regulate tumor growth and progression. However, the roles of ACTL6A in the development of ovarian cancer and the regulation of cancer glucose metabolism are mostly unknown. Here we show that ACTL6A is overexpressed in ovarian cancers compared with adjacent non-tumor tissues, and that ACTL6A overexpression correlates with poor prognosis. Silencing of ACTL6A in vitro inhibits proliferation, clonal growth, and migration, and decreases glucose utilization, lactate production, and pyruvate levels of ovarian cancer cells. We found a positive correlation between ACTL6A and PGK1 expression in ovarian cancer tissues. Enforced ACTL6A expression increased PGK1 expression, whereas knockdown of ACTL6A had the opposite effect. Altered ACTL6A expression inhibits the tumorigenicity of ovarian cancer cells in vivo by downregulating PGK1. In addition, the expression of ACTL6A is regulated by follicle-stimulating hormone (FSH) stimulation via PI3K/AKT pathway. Importantly, ACTL6A regulates FSH-enhanced glycolysis in ovarian cancer. Taken together, our findings highlight the critical role of ACTL6A in ovarian cancer development and identify its contribution to glucose metabolism of cancer cells.
P4HA2 is one of collagen prolyl 4-hydroxylase (P4H) isoform and increased in several types of human cancer. However, the role of P4HA2 during cervical tumorigenesis remains largely unknown. Here, we report that the protein level of P4HA2 is significantly increased in cervical cancer tissues. Silencing of P4HA2 inhibits cervical cancer cell proliferation, colony formation and migration. We also demonstrate decreased glucose uptake and lactate production in P4HA2 knockdown cells. Mechanistically, P4HA2 promotes cervical cancer cell glycolysis through upregulation of PGK1 and LDHA. We find a positive correlation between P4HA2 and PGK1/LDHA expression in cervical cancer tissues. Importantly, high expression of P4HA2, PGK1 or LDHA has a significantly shorter overall survival period and the survival prediction is enhanced by using combination of P4HA2 and PGK1/LDHA expression. Collectively, we identify P4HA2 as a regulator of glycolysis through PGK1 and LDHA, which may serve as a potential therapeutic target for cervical cancer.
Abstract Background The aim of this study was to investigate the associations of blood phosphorus levels with the risk of developing medial arterial calcification (MAC) in lower-limb arteries and diabetic foot (DF) in diabetes patients. We sought to enhance the understanding of the pathophysiology of diabetic complications and develop strategies to mitigate diabetes-related risks. Methods We conducted a retrospective analysis of 701 diabetic patients from the Department of Endocrinology at Sun Yat-Sen Memorial Hospital (2019–2023). We utilized multimodel-adjusted logistic regression to investigate the associations of serum phosphorus levels and the risk of developing MAC and DF. Restricted cubic spline plots were employed to model the relationships, and threshold analysis was used to identify inflection points. Subgroup analyses were performed to explore variations across different demographics. The diagnostic utility of phosphorus concentrations was assessed via the C index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results Of the 701 patients (mean age 63.9 years; 401 (57.20%) were male), 333 (47.50%) had MAC, and 329 (46.93%) had DF. After controlling for numerous confounding variables, each one-unit increase in phosphorus concentrations was associated with an increased risk of developing MAC (OR 2.65, 95% CI 1.97–3.57, p < 0.001) and DF (OR 1.54, 95% CI 1.09–2.18, p = 0.014). Phosphorus levels demonstrated a linear risk association, with risk not being uniform on either side of the inflection point, which was approximately 3.28 mg/dL for MAC and varied for DF (3.26 to 3.81 mg/dL). Adding the phosphorus as an independent component to the diagnostic model for MAC and DF increased the C index, NRI, and IDI to varying degrees. Conclusions Elevated serum phosphorus levels are significantly associated with an increased risk of developing MAC and DF among diabetic people. These findings suggest that phosphorus management could be integrated into routine diagnostic processes to improve the identification and management of lower-extremity diabetic complications. Graphical abstract
Ethnopharmacological relevance: Chaihu Qingwen granules (CHQW) is a classic formula for the treatment of respiratory diseases. Clinical observation shows that CHQW has good efficacy in treating cold, cough and fever.Aim of the studyThe aim of this study was to investigate the anti-inflammatory effect of CHQW on lipopolysaccharide (LPS)-induced acute lung injury (ALI) model in rats and to explore its potential mechanism, as well as to clarify its substance composition.Materials and Methods: Male SD rats were randomly divided into the blank group, the model group, the ibuprofen group, the Lianhua Qingwen capsule group and CHQW group (2, 4 and 8 g/kg, respectively). The LPS-induced acute lung injury (ALI) model in rats was established after pre-administration. The histopathological changes of lung and the levels of inflammatory factors in bronchoalveolar lavage fluid (BALF) and serum of ALI rats were observed. The inflammation-related proteins toll-like receptor 4 (TLR4), inhibitory kappa B alpha (IκBα), phospho-IκBα (p-IκBα), nuclear-factor-kappa B (NF-κB), and NLR family pyrin domain containing 3(NLRP3) expression levels were measured by western blotting analysis and immunohistochemical analysis. The chemical composition of CHQW was identified by liquid chromatography-quadrupole-time of flight-mass spectrometry (LC-Q-TOF-MS).Results: CHQW significantly ameliorated lung tissue pathological injury in LPS-induced ALI rats and decreased the release of inflammatory cytokines (interleukin-1β, interleukin-17 and tumor necrosis factor-α) in BALF and serum. In addition, CHQW decreased the expression of TLR4, p-IκBα and NF-κB proteins, increased the level of IκBα, regulated the TLR4/NF-κB signaling pathway, and inhibited the activation of NLRP3. The chemical components of CHQW were analyzed by LC-Q-TOF-MS, and a total of 48 components were identified by combining information from the literature, mainly flavonoids, organic acids, lignans, iridoids and phenylethanoid glycosides.Conclusion: The results of this study showed that the pretreatment of CHQW had a strong protective effect on LPS-induced ALI in rats, reducing lung tissue lesions and decreasing inflammatory cytokines released in BALF and serum. The protective mechanism of CHQW may be related to the inhibition of the TLR4 /NF-κB signaling pathway and NLRP3 activation.The main active ingredients of CHQW are flavonoids, organic acids, lignans, iridoids and phenylethanoid glycosides.
Objective To investigate the effect of compound Kushen injection combined with chemotherapy on the immune function in Non-small cell lung cancer(NSCLC)patient.Methods Totally 59 inoperable NSCLC patients were randomly divided into the treated group(n=29,treated with compound Kushen injection combined with chemotherapy)and the control group(n=30,treated with chemotherapy alone).Chemotherapy of NP protocol was applied to both groups,determined blood route,IgA,IgM,IgG,T cell subsets one day before chemotherapy and one week after chemotherapy from peripheral blood.Results The WBC and lymphocyte transformation rate of control group was(3.2±1.6)×109·L-1 and(9.1±2.4)%respectively after chemotherapy,that of treated group was(5.2±2.6)×109·L-1 and(19.5±2.6)%respectively,higher than the control group(P0.01).The CD4+ and CD8+ positive cell count(36.7±2.1)%and(38.5±1.7)%in treat group,higher than that in control group which were(30.2±1.3)%and(24.6±1.4)%)(P0.01),IgA,IgM,IgG of thymopentin treated group was significantly different compared with control therapy(P0.05).Conclusion Compound Kushen may alleviate toxicology reaction of chemotherapy,raise the white blood cell of patients and enhance cellular immunologic functions in the NSCLC patients.
OBJECTIVE Recent genome-wide association studies (GWAS) revealed that a 9p21.3 locus was associated with type 2 diabetes. In this study, we carried out a large-scale case-control study in the GeneID Chinese Han population to 1) further replicate the association of 9p21.3 type 2 diabetes GWAS single nucleotide polymorphisms (SNPs) and 2) assess the association of these SNPs with coronary artery disease. RESEARCH DESIGN AND METHODS Three SNPs (rs2383208, rs10811661, and rs10757283) were genotyped in two GeneID cohorts of 3,167 Chinese Han individuals. Case-control association design was used to determine the association of the SNPs with type 2 diabetes and coronary artery disease. Gensini scores were calculated in the coronary artery disease subjects and were tested for association with the variants. Multivariate logistic regressions were performed on association studies. RESULTS The association between two of the three SNPs and type 2 diabetes was replicated in the GeneID population (rs2383208, P = 0.936; rs10811661-T, P = 0.02, odds ratio [OR] = 1.23; rs10757283-C, P = 0.003, OR = 1.30). The same two SNPs also contributed to the risk of coronary artery disease (CAD) (rs10811661-T, P = 0.002, OR = 1.19; rs10757283-C, P = 0.003, OR = 1.18). In addition, rs10757283 was associated with severity of coronary atherosclerosis estimated by the Gensini scoring system (risk allele C, quantitative-trait regression adjusted P = 0.002). CONCLUSIONS For the first time to our knowledge, our results indicated that the same 9p21.3 locus, represented by SNPs rs10811661 and rs10757283, contributed to the risk of type 2 diabetes and coronary artery disease in our GeneID Chinese Han population.
It has been demonstrated in some studies that triterpenoid acid extract fromEriobotrya japonica leaf is beneficial to prevent hyperlipidemia or insulin resistance. However, the effect of triterpenoid acids in Eriobotrya japonica leaf on a series of typical symptoms of metabolic syndrome (MetS) has been rarely studied systematically. Therefore, the present study aims to systematically evaluate the effect of Eriobotrya japonica leaf triterpenoid acids (ELTA) on MetS and explore its potential mechanism. ELTA (HPLC purity 95.2 %) was prepared and administered orally (200 mg/kg) to C57BL/6 J mice fed with a high-fat diet (HFD) for 12 weeks. Pioglitazone (30 mg/kg) was used as a positive control drug. Food intake, body weight, total lipid in feces, lipid profiles, inflammatory factors in serum, hepatic glutathione, and lipid peroxide were measured. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed to evaluate insulin sensitivity. RT-qPCR and molecular docking were performed to explore the potential mechanism. ELTA administration reduced body weight gain, relative liver weight, and relative visceral adipose weight. The levels of serum total cholesterol, triglycerides, low-density lipoprotein cholesterol, hepatic total cholesterol, and hepatic triglycerides were also reduced. ELTA reduced the area under curve (AUC) of blood glucose curves in OGTT and ITT. Relative mRNA level analysis of genes related to MetS showed that ELTA can effectively increase the transcriptional levels of Nrf2, HO-1, PPAR-γ, GluT2, GK, FXR, while effectively decrease those of PTP1B, p65, TNF-α, IL-6, SREBP, 11βHSD-1. Molecular docking showed that the ligands in ELTA can bind to 11βHSD-1, GK, PPAR-γ, and JNK, the important targets involved in MetS. ELTA can effectively alleviate visceral central obesity, insulin resistance, dyslipidemia, oxidative stress, and inflammation of HFD-induced MetS in C57BL/6 J mice. This is possibly achieved by acting on 11βHSD-1, GK, PPAR-γ, and JNK.
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