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Background Cardiovascular disease, mainly atherosclerotic cardiovascular disease, is the first cause of death for urban and rural residents in China. Low density lipoprotein cholesterol is the pathogenic risk factor of ASCVD. Objective By establishing a new outpatient model for blood lipid management, to analyze the awareness rate of abnormal blood lipids in patients before and after the establishment of the new model, the proportion of rational drug use, patient compliance, and medication compliance rate. Methods From September 1, 2023 to February 28, 2024, has established a comprehensive outpatient model for managing blood lipid abnormalities based on scientific research projects by integrating medical resources. The model takes the outpatient service of "patients with dyslipidemia" as the carrier, and collaborates with specialized doctors and general practitioners to standardize the management of dyslipidemia patients, optimize the consultation and follow-up process, effectively screen the population with dyslipidemia, diagnose hyperlipidemia patients, and provide correct treatment methods. Results The model of patients with dyslipidemia included in the management of chronic diseases has shifted from a dispersed model to a comprehensive, standardized, and centralized management of lipid management outpatient services, and the number of patients managed has significantly increased compared to before. The proportion of standardized medication for first-time patients in our blood lipid management outpatient department has increased from 25.3% (147/580) to 30.3% (242/798), the proportion of adherence to medication has increased from 32.7% (190/580) to 41.6% (332/798), and the compliance rate of medication has increased from 15.8% (92/580) to 22.5% (180/798) (P

In patients with chronic kidney disease, the uremic toxin indoxyl sulfate (IS) accelerates kidney damage and the progression of cardiovascular disease. IS may contribute to vascular diseases by inducing inflammation in endothelial cells. Luteolin has documented antioxidant and anti‐inflammatory properties. This study aimed to investigate the effect of luteolin on IS‐mediated reactive oxygen species (ROS) production and intercellular adhesion molecule (ICAM‐1) and monocyte chemoattractant protein (MCP‐1) expression in EA.hy926 cells and the possible mechanisms involved. IS significantly induced ROS production (by 6.03‐fold, p < 0.05), ICAM‐1 (by 2.19‐fold, p < 0.05) and MCP‐1 protein expression (by 2.18‐fold, p < 0.05), and HL‐60 cell adhesion (by 31%, p < 0.05), whereas, luteolin significantly decreased IS‐induced ROS production, ICAM‐1 and MCP‐1 protein expression, and HL‐60 cell adhesion. Moreover, luteolin attenuated IS‐induced nuclear accumulation of p65 and c‐jun. Luteolin dose‐dependently increased heme oxygenase‐1 (HO‐1) expression and the maximum fold induction of HO‐1 by luteolin was 3.68‐fold (p < 0.05), whereas, HO‐1 knockdown abolished the suppression of ICAM‐1 and MCP‐1 expression by luteolin. Luteolin may protect against IS‐induced vessel damage by inducing HO‐1 expression in vascular endothelial cells, which suppresses nuclear factor kappa B (NF‐κB) and activator protein 1 (AP‐1) mediated ICAM‐1 and MCP‐1 expression. [ABSTRACT FROM AUTHOR]

Lipotoxicity leads to numerous metabolic disorders such as nonalcoholic steatohepatitis. Luteolin, apigenin, and chrysin are three flavones with known antioxidant and anti‐inflammatory properties, but whether they inhibit lipotoxicity‐mediated NLRP3 inflammasome activation was unclear. To address this question, we used J774A.1 macrophages and Kupffer cells stimulated with 100 μM palmitate (PA) in the presence or absence of 20 μM of each flavone. PA increased p‐PERK, p‐IRE1α, p‐JNK1/2, CHOP, and TXNIP as well as p62 and LC3‐II expression and induced autophagic flux damage. Caspase‐1 activation and IL‐1β release were also noted after 24 h of exposure to PA. In the presence of the PERK inhibitor GSK2656157, PA‐induced CHOP and TXNIP expression and caspase‐1 activation were mitigated. Compared with PA treatment alone, Bcl‐2 coupled to beclin‐1 was elevated and autophagy was reversed by the JNK inhibitor SP600125. With luteolin, apigenin, and chrysin treatment, PA‐induced ROS production, ER stress, TXNIP expression, autophagic flux damage, and apoptosis were ameliorated. Moreover, TXNIP binding to NLRP3 and IL‐1β release in response to LPS/PA challenge were reduced. These results suggest that luteolin, apigenin, and chrysin protect hepatic macrophages against PA‐induced NLRP3 inflammasome activation and autophagy damage by attenuating endoplasmic reticulum stress. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinase (MMP)-2 and -9, which degrade type IV collagen, are linked to cancer invasion and metastasis. Gene polymorphisms in MMP-2 and MMP-9 can influence their function, impacting cancer development and progression. This study analyzed the association between polymorphisms MMP-2 rs243865 (C-1306T), rs2285053 (C-735T), and MMP-9 rs3918242 (C-1562T) with serum concentrations of these enzymes in upper tract urothelial cancer (UTUC) patients. We conducted a case–control study with 218 UTUC patients and 580 healthy individuals in Taiwan. Genotyping was performed using PCR/RFLP on DNA from blood samples, and MMP-2 and MMP-9 serum levels and mRNA expressions in 30 UTUC patients were measured using ELISA and real-time PCR. Statistical analysis showed that MMP-2 rs2285053 and MMP-9 rs3918242 genotypes were differently distributed between UTUC patients and controls (p = 0.0199 and 0.0020). The MMP-2 rs2285053 TT genotype was associated with higher UTUC risk compared to the CC genotype (OR = 2.20, p = 0.0190). Similarly, MMP-9 rs3918242 CT and TT genotypes were linked to increased UTUC risk (OR = 1.51 and 2.92, p = 0.0272 and 0.0054). In UTUC patients, TT carriers of MMP-2 rs2285053 and MMP-9 rs3918242 showed higher mRNA and protein levels (p < 0.01). These findings suggest that MMP-2 rs2285053 and MMP-9 rs3918242 genotypes are significant markers for UTUC risk and metastasis in Taiwan. [ABSTRACT FROM AUTHOR]

Oral cancer ranks sixth among Taiwan's top 10 cancers and most patients with poor prognosis acquire metastases. The essential fatty acid alpha-linolenic acid (ALA) has been found to diminish many cancer properties. However, the anti-cancer activity of ALA in oral cancer has yet to be determined. We examined the mechanisms underlying ALA inhibition of metastasis and induction of apoptotic cell death in oral squamous cell carcinoma (OSCC). Migration and invasion assays confirmed the cancer cells' EMT capabilities, whereas flow cytometry and Western blotting identified molecular pathways in OSCC. ALA dramatically reduced cell growth in a concentration-dependent manner according to the findings. Low concentrations of ALA (100 or 200 μM) inhibit colony formation, the expression of Twist and EMT-related proteins, the expression of MMP2/-9 proteins, and enzyme activity, as well as cell migration and invasion. Treatment with high concentrations of ALA (200 or 400 μM) greatly increases JNK phosphorylation and c-jun nuclear accumulation and then upregulates the FasL/caspase8/caspase3 and Bid/cytochrome c/caspase9/caspase3 pathways, leading to cell death. Low concentrations of ALA inhibit SAS and GNM cell migration and invasion by suppressing Twist and downregulating EMT-related proteins or by decreasing the protein expression and enzyme activity of MMP-2/-9, whereas high concentrations of ALA promote apoptosis by activating the JNK/FasL/caspase 8/caspase 3-extrinsic pathway and the Bid/cytochrome c/caspase 9 pathway. ALA demonstrates potential as a treatment for OSCC patients. [ABSTRACT FROM AUTHOR]

Andrographolide (AND) is a bioactive component of the herb Andrographis paniculata and a well-known anti-inflammatory agent. Atherosclerosis is a chronic inflammatory disease of the vasculature, and oxidized LDL (oxLDL) is thought to contribute heavily to atherosclerosis-associated inflammation. The aim of this study was to investigate whether AND mitigates oxLDL-mediated foam cell formation and diet-induced atherosclerosis (in mice fed a high-fat, high-cholesterol, high-cholic acid [HFCCD] diet) and the underlying mechanisms involved. AND attenuated LPS/oxLDL-mediated foam cell formation, IL-1 β mRNA and protein (p37) expression, NLR family pyrin domain containing 3 (NLRP3) mRNA and protein expression, caspase-1 (p20) protein expression, and IL-1 β release in BMDMs. Treatment with oxLDL significantly induced protein and mRNA expression of CD36, lectin-like oxLDL receptor-1 (LOX-1), and scavenger receptor type A (SR-A), whereas pretreatment with AND significantly inhibited protein and mRNA expression of SR-A only. Treatment with oxLDL significantly induced ROS generation and Dil-oxLDL uptake; however, pretreatment with AND alleviated oxLDL-induced ROS generation and Dil-oxLDL uptake. HFCCD feeding significantly increased aortic lipid accumulation, ICAM-1 expression, and IL-1 β mRNA expression, as well as blood levels of glutamic pyruvic transaminase (GPT), total cholesterol, and LDL-C. AND co-administration mitigated aortic lipid accumulation, the protein expression of ICAM-1, mRNA expression of IL-1 β and ICAM-1, and blood levels of GPT. These results suggest that the working mechanisms by which AND mitigates atherosclerosis involve the inhibition of foam cell formation and NLRP3 inflammasome-dependent vascular inflammation as evidenced by decreased SR-A expression and IL-1 β release, respectively. [ABSTRACT FROM AUTHOR]

Background: Protective effects of Gynura bicolor aqueous extract (GAE) at three concentrations upon nerve growth factor (NGF) differentiated-PC12 cells against H2O2 induced injury were examined. Methods: NGF differentiated-PC12 cells were treated with GAE at 0.25%, 0.5% or 1%. 100 μM H2O2 was used to treat cells with GAE pre-treatments. After incubating at 37 °C for 12 hr, experimental analyses were processed. Results: H2O2 exposure decreased cell viability, increased plasma membrane damage, suppressed Bcl-2 mRNA expression and enhanced Bax mRNA expression. GAE pre-treatments reversed these changes. H2O2 exposure reduced mitochondrial membrane potential, lowered Na+-K+-ATPase activity, and increased DNA fragmentation and Ca2+ release. GAE pre-treatments attenuated these alterations. H2O2 stimulated the production of reactive oxygen species (ROS), interleukin (IL)-1beta, IL-6 and tumor necrosis factor-alpha, lowered glutathione content, and reduced glutathione peroxidase (GPX) and catalase activities. GAE pretreatments maintained GPX and catalase activities; and concentration-dependently diminished the generation of ROS and inflammatory cytokines. H2O2 enhanced mRNA expression of nuclear factor kappa (NF-κ) B and p38. GAE pre-treatments decreased mRNA expression of NF-κB and p38. Conclusion: These findings suggested that GAE might be a potent neuronal protective agent.

The content of nitric oxide (NO), 3-nitrotyrosine, advanced glycation endproducts (AGEs) and trans fatty acids (TFAs) in 16 kinds of cured meat products was examined. Results showed that NO and 3-nitrotyrosine levels were in the range of non-detectable to 4.6 μM/mg protein, and non-detectable to 0.49 nmol/mg protein, respectively. Carboxymethyllysine could be detected in 13 kinds of cured meat products; its content was in the range of 48-306 μg/100 g meat. Pentosidine was found in 14 kinds of meat products, in the range of 109-631 μg/100 g meat. Furosine was presented in all test meat samples, in the range of 156-676 μg/100 g meat. Palmitelaidic acid was found in 3 kinds of meat product, and the content was in the range of 0.59-0.71%. Vaccenic acid was presented in 9 kinds of meat products; its content was in the range of 0.89-1.47%. Elaidic acid was detected in 5 kinds of meat products, and the content was in the range of 0.67-1.21%. Because NO, 3-nitrotyrosine and AGEs might have adverse impact upon health, people with certain healthy conditions should carefully consider the frequency and amount of consumption for these cured meat products.

Andrographolide is the major bioactive component of the herb Andrographis paniculata and is a potent anti-inflammatory agent. Obesity leads to an excess of free fatty acids, particularly palmitic acid (PA), in the circulation. Obesity also causes the deposition of ectopic fat in nonadipose tissues, which leads to lipotoxicity, a condition closely associated with inflammation. Here, we investigated whether andrographolide could inhibit PA-induced inflammation by activating autophagy, activating the antioxidant defense system, and blocking the activation of the NLRP3 inflammasome. Bone marrow-derived macrophages (BMDMs) were primed with lipopolysaccharide (LPS) and then activated with PA. LPS/PA treatment increased both the mRNA expression of NLRP3 and IL-1 β and the release of IL-1 β in BMDMs. Andrographolide inhibited the LPS/PA-induced protein expression of caspase-1 and the release of IL-1 β. Furthermore, andrographolide attenuated LPS/PA-induced mtROS generation by first promoting autophagic flux and catalase activity, and ultimately inhibiting activation of the NLRP3 inflammasome. Our results suggest that the mechanisms by which andrographolide downregulates LPS/PA-induced IL-1 β release in BMDMs involve promoting autophagic flux and catalase activity. Andrographolide may thus be a candidate to prevent obesity- and lipotoxicity-driven chronic inflammatory disease. [ABSTRACT FROM AUTHOR]

Pro-inflammatory cytokines interfere with blood glucose homeostasis, which leads to hyperglycemia. Andrographis paniculata (AP) has been shown to possess anti-inflammatory activity and to reduce blood glucose levels in diabetes. The two major bioactive diterpenoids in AP, andrographolide (AND) and 14-deoxy-11,12-didehydroandrographolide (deAND), have potent anti-inflammatory activity. We studied whether APE (an ethanolic extract of AP), AND, and deAND could improve a high-fat diet (HFD)-induced hyperglycemia in vivo and TNF α -induced impairment of insulin signaling in vitro. Male C57BL/6JNarl mice were fed a normal diet (ND) or the HFD, and the fatty mice were treated with APE, deAND, or AND for 16 weeks. 3T3-L1 cells were used to study the underlying mechanisms by which APE, deAND, or AND attenuated TNF α -induced insulin resistance. The HFD significantly induced obesity, hyperglycemia, insulin resistance, and inflammation, whereas APE and deAND significantly ameliorated HFD-induced obesity, hyperglycemia, insulin resistance, and TNF α production. The HFD significantly impaired insulin signaling by decreasing the protein expression of p-IRS1 tyr632 and p-AKT ser473, as well as the membrane translocation of GLUT4 in response to insulin stimulation in epididymal adipose tissue. HFD-impaired the membrane translocation of GLUT4 was significantly reversed by deAND and APE. In addition, deAND and APE markedly reversed the detrimental effect of TNF α on the insulin signaling pathway and glucose uptake in 3T3-L1 cells. Despite no significant positive effect on p-AS160, a trend for recovery by deAND and APE was observed. These results suggest that deAND and APE protect against HFD-induced insulin resistance by ameliorating inflammation-driven impairment of insulin sensitivity. [ABSTRACT FROM AUTHOR]