Search Results (15)

Tirzepatide is a long-acting agonist for the glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors approved for the treatment of type 2 diabetes mellitus, weight management in obese patients, or overweight patients with at least one weight-related comorbid condition. The clinical effects of tirzepatide are demonstrated by improved glycemic control, reduced overall appetite, decreased food intake, and body weight. Several studies indicated that the vasculoprotective effects and anti-atherosclerotic potential of tirzepatide extend far beyond glycemic control. Tirzepatide stimulates the mobilization and function of endothelial progenitor cells, which facilitates vascular repair and mitigates hyperglycemia-induced damage. Tirzepatide enhances the activity of endothelial nitric oxide synthase, reduces the activity of endothelial activation molecules such as intercellular adhesion molecule 1 and vascular cell adhesion molecule 1, promotes vasodilation, and reduces peripheral vascular resistance. Furthermore, the drug inhibits inflammation by suppressing the expression of pro-inflammatory cytokines, such as tumor necrosis factor α, interleukin-1β, and interleukin-6. Moreover, tirzepatide improves lipid profiles by decreasing total cholesterol, low-density lipoprotein cholesterol, and triglycerides, while increasing high-density lipoprotein cholesterol. By improving endothelial function, reducing inflammation, and lowering body weight, tirzepatide lowers both systolic and diastolic blood pressure. This article summarizes the data with special emphasis on the mechanisms underlying the anti-atherosclerotic and vasoprotective effects of tirzepatide, based on studies conducted to date. Full article

Background and Objectives: Metabolic syndrome (MetS) is characterized by a cluster of metabolic abnormalities, including abdominal obesity, hyperglycemia, insulin resistance, dyslipidemia, and hypertension. Growing evidence suggests that these components may contribute to the development of gastrointestinal (GI) malignancies. This review aims to explore the association between MetS and GI cancers, including esophageal, gastric, pancreatic, and colorectal cancers. Materials and Methods: A narrative literature review was conducted using PubMed, incorporating 22 sources published between 1991 and 2024. Search terms included “gastrointestinal malignant tumors”, “metabolic syndrome”, “diabetes mellitus”, and “obesity”. Priority was given to large-scale studies from Europe, America, and Asia. Case reports, commentaries, and conference abstracts were excluded. Results: By analyzing the available literature data, this study determined that hyperinsulinemia (IGF-1 pathway), hyperglycemia, and obesity (>102 cm in men and >88 cm in women) are highly associated with the development of esophageal cancer (primarily with Barret’s long and short segment as precancerosis), gastric cancer (through reactive oxygen species), and both pancreatic (1.5–2.4 higher risk) and colorectal cancer (30% higher risk). Patients with a high BMI (>40 kg/m²) show a 20%- or 1.18-times greater risk of developing colorectal cancer and a 1.72-times higher risk of developing pancreatic cancer. There is not enough evidence on the specific influence of hypertriglyceridemia, low HDL cholesterol, and high blood pressure on the development of gastrointestinal malignancy. However, those three conditions have shown a low to moderate association (from 6% to 12%) with the development of colorectal cancer. Conclusions: Metabolic syndrome (MetS) is increasingly being recognized as a significant risk factor for the development and progression of gastrointestinal cancers. Key components such as obesity, hyperglycemia, insulin resistance, and type 2 diabetes mellitus appear to contribute to carcinogenesis through mechanisms involving chronic inflammation, oxidative stress, and immune dysregulation. Further research is needed to clarify the biological pathways linking MetS to gastrointestinal malignancies and to inform effective prevention strategies. Full article

Background: The World Health Organization has indicated that airport noise is strongly associated with cardiovascular disease, with vascular inflammation identified as the primary mechanism. Therefore, long-term exposure to airport noise is considered far more harmful than other types of noise. However, there remains a lack of research into the mechanisms underlying long-term exposure to airport noise and harm to the human body. Methods: A mouse model was established and exposed to airport noise at a maximum sound pressure level of 95 dB(A) and an equivalent continuous sound pressure level of 72 dB(A) for 12 h per day over a period of 100 days. Quantitative polymerase chain reaction (qPCR) was used to detect the mRNA expression levels of pro-inflammatory and anti-inflammatory factors. Enzyme-linked immunosorbent assay (ELISA) was used to detect LPS, LTA, TMA, and TMAO levels. Intestinal flora composition was analyzed by 16S rDNA sequencing, and targeted metabolomics was employed to determine the levels of serum short-chain fatty acids. Results: Long-term airport noise exposure significantly increased systolic blood pressure, diastolic blood pressure, and mean blood pressure (p < 0.05); significantly increased the mRNA expression levels of oxidative stress parameters (nuclear matrix protein 2, 3-nitrotyrosine, and monocyte chemoattractant protein-1) (p < 0.05); significantly increased pro-inflammatory factors (interleukin 6 and tumor necrosis factor alpha) (p < 0.05); significantly decreased the mRNA expression level of anti-inflammatory factor interleukin 10 (p < 0.05); and significantly increased the content of LPS and LTA (p < 0.05). The composition of the main flora in the intestinal tract was structurally disordered, and there were significant differences between the noise-exposed and control groups at the levels of the phylum, family, and genus of bacteria. β-diversity of the principal component analysis diagrams was clearly distinguished. Compared with those of the control group, TMA-producing bacteria and levels of TMA and TMAO were significantly reduced, and the serum ethanoic acid and propanoic acid levels of the noise-exposed group were significantly decreased (p < 0.05). Conclusions: Long-term airport noise exposure causes significant elevation of blood pressure and structural disruption in the composition of the intestinal flora in mice, leading to elevated levels of oxidative stress and inflammation, resulting in metabolic disorders that lead to significant changes in the production of metabolites. Full article

The therapeutic potential of cold physical gas plasma operated at atmospheric pressure in oncology has been thoroughly demonstrated in numerous preclinical studies. The cytotoxic effect on malignant cells has been attributed mainly to biologically active plasma-generated compounds, namely, reactive oxygen and nitrogen species. The intracellular accumulation of reactive oxygen and nitrogen species interferes strongly with the antioxidant defense system of malignant cells, activating multiple signaling cascades and inevitably leading to oxidative stress-induced cell death. This study aims to determine whether plasma-induced cancer cell death operates through a universal molecular mechanism that is independent of the cancer cell type. Using whole transcriptome data, we sought to investigate the activation mechanism of plasma-treated samples in patient-derived prostate cell cultures, melanoma, breast, lymphoma, and lung cancer cells. The results from the standardized single-cohort gene expression analysis and parallel multi-cohort meta-analysis strongly indicate that plasma treatment globally induces cancer cell death through immune-mediated mechanisms, such as interleukin signaling, Toll-like receptor cascades, and MyD88 activation leading to pro-inflammatory cytokine release and tumor antigen presentation. Full article

Human serum albumin (HSA) has an important antioxidant activity due to the presence of the reduced cysteine at position 34, which represents the most abundant free thiol in the plasma. In oxidative-based diseases, HSA undergoes S-thiolation (THIO-HSA) with changes in the antioxidant function of albumin that could contribute to the progression of the disease. The aim of this study was to verify, for the first time, the different burdens of THIO-HSA, glycated HSA (GLY-HSA), and advanced glycation end products (AGE) accumulation both in type 2 diabetes mellitus (T2DM) patients and in non-diabetic patients, with or without coronary heart disease (CHD). In this study, we assessed the presence of modified forms of HSA, THIO-HSA, and GLY-HSA by means of mass spectrometry in 33 patients with both T2DM and CHD, in 31 patients with T2DM and without CHD, in 30 patients without diabetes with a history of CHD, and 27 subjects without diabetes and CHD. All the patients’ anthropometric and clinical data were recorded including age, sex, duration of diabetes, body mass index (BMI), blood pressure, and history of CHD defined with anamnestic data. Metabolic parameters, such as fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), lipids, pentosidine, AGE, receptor for advanced glycation end-products (RAGE) and its soluble form (sRAGE), were measured. AGE and pentosidine are significantly higher in T2DM patients with and without CHD with respect to non-diabetic patients with CHD and control subjects. RAGE levels are significantly higher in T2DM patients with respect to non-diabetic patients, and among T2DM patients, the group with CHD showed significantly higher RAGE levels than those without CHD (217 ± 171 pg/mL and 140 ± 61 pg/mL, respectively). Albumin isoforms discriminate between non-diabetic patients with CHD and T2DM patients with and without CHD and control subjects, with GLY-HSA levels higher in T2DM with and without CHD, and THIO-HSA higher in CHD patients without T2DM. Finally, we demonstrated that the oxidized forms of HSA can increase the expression of the inflammatory cytokine Tumor Necrosis Factor-alpha (TNFα) in monocytic cells. In patients with CHD, GLY-HSA and THIO-HSA have a different prevalent distribution, the first one prevailing in patients with T2DM and the second one in patients without T2DM. These findings suggest that albumin quality and homeostasis balance between glyco-oxidation and thiolation might have an impact on the antioxidant defense system in cardiovascular diseases. Full article

Cannabidiol (CBD) is a plant-derived compound with antioxidant and anti-inflammatory properties. Pulmonary hypertension (PH) is still an incurable disease. CBD has been suggested to ameliorate monocrotaline (MCT)-induced PH, including reduction in right ventricular systolic pressure (RVSP), a vasorelaxant effect on pulmonary arteries and a decrease in the white blood cell count. The aim of our study was to investigate the effect of chronic administration of CBD (10 mg/kg daily for 21 days) on the parameters of oxidative stress and inflammation in the lungs of rats with MCT-induced PH. In MCT-induced PH, we found a decrease in total antioxidant capacity (TAC) and glutathione level (GSH), an increase in inflammatory parameters, e.g., tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), nuclear factor kappa B (NF-κB), monocyte chemoattractant protein-1 (MCP-1), and cluster of differentiation 68 (CD68), and the overexpression of cannabinoid receptors type 1 and 2 (CB₁-Rs, CB₂-Rs). Administration of CBD increased TAC and GSH concentrations, glutathione reductase (GSR) activity, and decreased CB₁-Rs expression and levels of inflammatory mediators such as TNF-α, IL -1β, NF-κB, MCP-1 and CD68. In conclusion, CBD has antioxidant and anti-inflammatory effects in MCT-induced PH. CBD may act as an adjuvant therapy for PH, but further detailed preclinical and clinical studies are recommended to confirm our promising results. Full article

The purpose of this study was to analyze the oxidative stress level and inflammatory status of saliva in the presence of certain materials used for obtaining interim prosthetic restorations. Four types of interim resin materials were investigated: a pressure/heat-cured acrylic resin (Superpont C+B, SpofaDental a.s Czech Republic, /KaVo Kerr Group), a milled resin (Telio CAD polymethyl methacrylate, Ivoclar Vivadent AG, Liechtenstein), a 3D printed resin (NextDent C&B MFH, NextDent by 3D Systems, the Netherlands), and a pressure/heat-cured micro-filled indirect composite resin (SR Chromasit, Ivoclar Vivadent AG, Liechtenstein). The disk-shaped resin samples (30 mm diameter, 2 mm high) were obtained in line with the producers’ recommendations. The resulting resin specimens were incubated with saliva samples collected from twenty healthy volunteers. In order to analyze the antioxidant activity of the tested materials, certain salivary parameters were evaluated before and after incubation: uric acid, gamma glutamyl transferase (GGT), oxidative stress responsive kinase-1 (OXSR-1), and total antioxidant capacity (TAC); the salivary levels of tumor necrosis factor (TNFα) and interleukin-6 (IL-6) (inflammatory markers) were measured as well. The obtained results are overall favorable, showing that the tested materials did not cause significant changes in the salivary oxidative stress level and did not influence the inflammatory salivary status. Full article

Adenine nucleotide translocase 1 (ANT1) transfers ATP and ADP over the mitochondrial inner membrane and thus supplies the cell with energy. This study analyzed the role of ANT1 in the immune response of ischemic heart tissue. Ischemic ANT1 overexpressing hearts experienced a shift toward an anti-inflammatory immune response. The shift was characterized by low interleukin (IL)-1β expression and M1 macrophage infiltration, whereas M2 macrophage infiltration and levels of IL-10, IL-4, and transforming growth factor (TGFβ) were increased. The modulated immune response correlated with high mitochondrial integrity, reduced oxidative stress, low left ventricular end-diastolic heart pressure, and a high survival rate. Isolated ANT1-transgenic (ANT1-TG) cardiomyocytes expressed low levels of pro-inflammatory cytokines such as IL-1α, tumor necrosis factor α, and TGFβ. However, they showed increased expression and cellular release of anti-inflammatory immunomodulators such as vascular endothelial growth factor. The secretome from ANT1-TG cardiomyocytes initiated stress resistance when applied to ischemic wild-type cardiomyocytes and endothelial cells. It additionally prevented macrophages from expressing pro-inflammatory cytokines. Additionally, ANT1 expression correlated with genes that are related to cytokine and growth factor pathways in hearts of patients with ischemic cardiomyopathy. In conclusion, ANT1-TG cardiomyocytes secrete soluble factors that influence ischemic cardiac cells and initiate an anti-inflammatory immune response in ischemic hearts. Full article

Polycystic ovary syndrome (PCOS) is a one of the most common endocrine disorders, with a prevalence rate of 5–10% in reproductive aged women. It’s characterized by (1) chronic anovulation, (2) biochemical and/or clinical hyperandrogenism, and (3) polycystic ovarian morphology. PCOS has significant clinical implications and can lead to health problems related to the accumulation of adipose tissue, such as obesity, insulin resistance, metabolic syndrome, and type 2 diabetes. There is also evidence that PCOS patients are at higher risk of cardiovascular diseases, atherosclerosis, and high blood pressure. Several studies have reported the association between polycystic ovary syndrome (PCOS) and low-grade chronic inflammation. According to known data, inflammatory markers or their gene markers are higher in PCOS patients. Correlations have been found between increased levels of C-reactive protein (CRP), interleukin 18 (IL-18), tumor necrosis factor (TNF-α), interleukin 6 (IL-6), white blood cell count (WBC), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α) in the PCOS women compared with age- and BMI-matched controls. Women with PCOS present also elevated levels of AGEs and increased RAGE (receptor for advanced glycation end products) expression. This chronic inflammatory state is aggravating by obesity and hyperinsulinemia. There are studies describing mutual impact of hyperinsulinemia and obesity, hyperandrogenism, and inflammatory state. Endothelial cell dysfunction may be also triggered by inflammatory cytokines. Many factors involved in oxidative stress, inflammation, and thrombosis were proposed as cardiovascular risk markers showing the endothelial cell damage in PCOS. Those markers include asymmetric dimethylarginine (ADMA), C-reactive protein (CRP), homocysteine, plasminogen activator inhibitor-I (PAI-I), PAI-I activity, vascular endothelial growth factor (VEGF) etc. It was also proposed that the uterine hyperinflammatory state in polycystic ovary syndrome may be responsible for significant pregnancy complications ranging from miscarriage to placental insufficiency. In this review, we discuss the most importance evidence concerning the role of the process of chronic inflammation in pathogenesis of PCOS. Full article

In this study, we examine whether Clitoria ternatea Linn. (CT) can prevent Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced cardiac and vascular dysfunction in rats. Male Sprague Dawley rats were given L-NAME (40 mg/kg, drinking water) and orally administered with CT extract (300 mg/kg/day) or lisinopril (2.5 mg/kg/day) for 5 weeks. The main phytochemical components of the CT extract were found to be flavonoids. The CT extract alleviated the high blood pressure in rats receiving L-NAME. Decreased vasorelaxation responses to acetylcholine and enhanced contractile responses to sympathetic nerve stimulation in aortic rings and mesenteric vascular beds of L-NAME treated rats were ameliorated by CT extract supplementation. Left ventricular hypertrophy and dysfunction were developed in L-NAME rats, which were partially prevented by CT extract treatment. The CT extract alleviated upregulated endothelial nitric oxide synthase expression, decreased plasma nitrate/nitrite levels, and increased oxidative stress in L-NAME rats. It suppressed high levels of serum angiotensin-converting enzyme activity, plasma angiotensin II, and cardiac angiotensin II type 1 receptor, NADPH oxidases 2, nuclear factor-kappa B, and tumor necrosis factor-alpha expression. The CT extract, therefore, partially prevented L-NAME-induced hypertension and cardiovascular alterations in rats. These effects might be related to a reduction in the oxidative stress and renin–angiotensin system activation due to L-NAME in rats. Full article

Vildagliptin is a representative of Dipeptidyl Peptidase-4 (DPP-4) inhibitors, antihyperglycemic drugs, approved for use as monotherapy and combination therapy in type 2 diabetes mellitus. By inhibiting enzymatic decomposition, DPP-4 inhibitors increase the half-life of incretins such as GLP-1 (Glucagon-like peptide-1) and GIP (Gastric inhibitors polypeptide) and prolong their action. Some studies present results suggesting the anti-sclerotic and vasculoprotective effects of vildagliptin reaching beyond glycemic control. Vildagliptin is able to limit inflammation by suppression of the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathway and proinflammatory agents such as TNF-α (tumor necrosis factor α), IL-1β (Interleukin-1β), and IL-8 (Interleukin 8). Moreover, vildagliptin regulates lipid metabolism; attenuates postprandial hypertriglyceridemia; and lowers serum triglycerides, apolipoprotein B, and blood total cholesterol levels. This DPP-4 inhibitor also reduces macrophage foam cell formation, which plays a key role in atheromatous plaque formation and stability. Vildagliptin reduces vascular stiffness via elevation of nitric oxide synthesis, improves vascular relaxation, and results in reduction in both systolic and diastolic blood pressure. Treatment with vildagliptin lowers the level of PAI-1 presenting possible antithrombotic effect. By affecting the endothelium, inflammation, and lipid metabolism, vildagliptin may affect the development of atherosclerosis at its various stages. The article presents a summary of the studies assessing vasculoprotective effects of vildagliptin with special emphasis on atherogenesis. Full article

Hypercholesterolemia may be causally related to heart failure with preserved ejection fraction (HFpEF). We aimed to establish a HFpEF model associated with hypercholesterolemia and type 2 diabetes mellitus by feeding a high-sucrose/high-fat (HSHF) diet to C57BL/6J low-density lipoprotein receptor (LDLr)^−/− mice. Secondly, we evaluated whether cholesterol-lowering adeno-associated viral serotype 8 (AAV8)-mediated LDLr gene transfer prevents HFpEF. AAV8-LDLr gene transfer strongly (p < 0.001) decreased plasma cholesterol in standard chow (SC) mice (66.8 ± 2.5 mg/dl versus 213 ± 12 mg/dl) and in HSHF mice (84.6 ± 4.4 mg/dl versus 464 ± 25 mg/dl). The HSHF diet induced cardiac hypertrophy and pathological remodeling, which were potently counteracted by AAV8-LDLr gene transfer. Wet lung weight was 19.0% (p < 0.001) higher in AAV8-null HSHF mice than in AAV8-null SC mice, whereas lung weight was normal in AAV8-LDLr HSHF mice. Pressure–volume loop analysis was consistent with HFpEF in AAV8-null HSHF mice and showed a completely normal cardiac function in AAV8-LDLr HSHF mice. Treadmill exercise testing demonstrated reduced exercise capacity in AAV8-null HSHF mice but a normal capacity in AAV8-LDLr HSHF mice. Reduced oxidative stress and decreased levels of tumor necrosis factor-α may mediate the beneficial effects of cholesterol lowering. In conclusion, AAV8-LDLr gene therapy prevents HFpEF. Full article

Anticancer metallodrugs that aim to physiological characters unique to tumor microenvironment are expected to combat drug tolerance and side-effects. Recently, owing to the fact that reactive oxygen species’ is closely related to the development of tumors, people are committed to developing metallodrugs with the capacity of improving the level of reactive oxygen species level toinduce oxidative stress in cancer cells. Herein, we demonstrated that peptide templated gold clusters with atomic precision preferably catalyze the transformation of hydrogen peroxide into superoxide anion in oxidative pressure-type tumor cells. Firstly, we successfully constructed gold clusters by rationally designing peptide sequences which targets integrin α_νβ₃ overexpressed on glioblastoma cells. The superoxide anion, radical derived from hydrogen peroxide and catalyzed by gold clusters, was confirmed in vitro under pseudo-physiological conditions. Then, kinetic parameters were evaluated to verify the catalytic properties of gold clusters. Furthermore, these peptide decorated clusters can serve as special enzyme-like catalyst to convert endogenous hydrogen peroxide into superoxide anion, elevated intracellular reactive oxygen species levels, lower mitochondrial membrane potential, damage biomacromolecules, and trigger tumor cell apoptosis consequently. Full article

Gestational diabetes mellitus (GDM) carries many risks, where high blood pressure, preeclampsia and future type II diabetes are widely acknowledged, but less focus has been placed on its effect on cognitive function. Although the multifactorial pathogenesis of maternal cognitive impairment is not completely understood, it shares several features with type 2 diabetes mellitus (T2DM). In this review, we discuss some key pathophysiologies of GDM that may lead to cognitive impairment, specifically hyperglycemia, insulin resistance, oxidative stress, and neuroinflammation. We explain how these incidents: (i) impair the insulin-signaling pathway and/or (ii) lead to cognitive impairment through hyperphosphorylation of τ protein, overexpression of amyloid-β and/or activation of microglia. The aforementioned pathologies impair the insulin-signaling pathway primarily through serine phosphorylation of insulin receptor substances (IRS). This then leads to the inactivation of the phosphatidylinositol 3-kinase/Protein kinase B (PI3K/AKT) signaling cascade, which is responsible for maintaining brain homeostasis and normal cognitive functioning. PI3K/AKT is crucial in maintaining normal cognitive function through the inactivation of glycogen synthase kinase 3β (GSκ3β), which hyperphosphorylates τ protein and releases pro-inflammatory cytokines that are neurotoxic. Several biomarkers were also highlighted as potential biomarkers of GDM-related cognitive impairment such as AGEs, serine-phosphorylated IRS-1 and inflammatory markers such as tumor necrosis factor α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), leptin, interleukin 1β (IL-1β), and IL-6. Although GDM is a transient disease, its complications may be long-term, and hence increased mechanistic knowledge of the molecular changes contributing to cognitive impairment may provide important clues for interventional strategies. Full article

Liubao tea is a type of traditional Chinese tea, belonging to the dark teas. This study is a basic research of the contained polyphenols (active substances) and detected preventive effects of polyphenols of raw Liubao tea (PRLT) on mouse gastric injuries induced by HCl/ethanol. High-pressure liquid chromatography was used to analyze the components of PRLT. Furthermore, a mouse gastric injury model was established to observe the preventive effects. PRLT was shown to contain gallic acid, EGC (epigallocatechin), catechin, caffeine, EC (epicatechin), EGCG (epigallocatechin gallate), GCG (gallocatechin gallate), and ECG (epicatechin gallate). The results of the in vivo study indicate that PRLT can inhibit the observed increase of gastric juice volume and decrease of gastric juice pH caused by gastric injury. PRLT can decrease the serum levels of IL-6 (interleukin-6), IL-12 (interleukin-12), TNF-α (tumor necrosis factor-α), and IFN-γ (interferon-γ) in mice with gastric injuries. Moreover, it can also increase the serum levels of SS (somatostatin) and VIP (vasoactive intestinal peptide) and reduce the serum levels of both SP (substance P) and ET-1 (endothelin-1). PRLT was also shown to increase SOD (superoxide dismutase) and GSH (glutathione) levels and decrease MDA (malondialdehyde) level. The detection of mRNA and protein in gastric tissues indicates that PRLT could also up-regulate the expression of Cu/Zn-SOD (copper/zinc superoxide dismutase), Mn-SOD (manganese superoxide dismutase), CAT (catalase), nNOS (neuronal nitric oxide synthase), and eNOS (endothelial nitric oxide synthase) and down-regulate the expression of both iNOS (inducible nitric oxide synthase) and COX-2 (cyclooxygenase-2). Thus, PRLT possess a good preventive effect on gastric injury, which is directly related to the contained active substance. PRLT show good anti-oxidative and preventive effect in gastric injury and offer promising application value. Full article