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y be of use in prevention of cardiovascular diseases.

In acute coronary syndrome (ACS) patients the focus is on major conventional risk factors - CRF [diabetes, hypertension, elevated low-density cholesterol (LDL-C) and smoking] whereas others - specific metabolic risk factors - MRF [high-density lipoprotein cholesterol (HDL-C), body-mass index (BMI), waist-hip ratio (WHR), and triglycerides, and HbA1c get less attention.

This is a prospective case-control observational study from 15 tertiary care hospitals in India. CRF and MRF in patients presenting with first incidence of ACS (n=2153) were compared with matched controls (n=1210).

Propensity score matching (PSM) yielded 1193 cases and matched 1210 controls. Risk factor prevalence in cases vs. controls were CRF hypertension - 39.4% vs 16.4% (p<0.0001), diabetes - 42.6% vs 12.7% (p<0.0001), smoking - 28.3% vs 9.3% (p<0.0001) and elevated LDL-C - 70.2% vs 57.9% (p<0.0001). MRF High BMI - 54.7% vs 55.1% (p=0.84), increased waist hip ratio 79.5% vs 63.6% (p<0.0001), high HbA1c - 37.8% vs 14.9% (p<0.0001), low HDL-C - 56.2% vs 42.8% (p<0.0001) and elevated triglycerides - 49.7% vs 44.2% (p=0.007). Adjusted Odds ratios by multivariate analysis were CRF hypertension - 2.3 (p<0.001), diabetes - 4.7 (p<0.001), high LDL-C - 3.3 (p<0.001) and smoking- 6.3 (p<0.001). MRF High waist hip ratio - 2.4 (p<0.001) high HbA1c - 3.2 (p<0.001), low HDL-C 2.2 (p<0.001) and elevated triglycerides - 0.878p=0.17.

In India, the risk of ACS conferred by specific metabolic risk factors (High waist hip ratio, Low HDL-C and High HbA1c) is comparable to that caused by CRF.

In India, the risk of ACS conferred by specific metabolic risk factors (High waist hip ratio, Low HDL-C and High HbA1c) is comparable to that caused by CRF.Understanding the lipid arrangement within the skin's outermost layer, the stratum corneum (SC), is important for advancing knowledge on the skin barrier function. The SC lipid matrix consists of ceramides (CERs), cholesterol, and free fatty acids, which form unique crystalline lamellar phases, referred to as the long periodicity phase (LPP) and short periodicity phases. As the SC lipid composition is complex, lipid model systems that mimic the properties of native SC are used to study the SC lipid organization and molecular arrangement. In previous studies, such lipid models were used to determine the molecular organization in the trilayer structure of the LPP unit cell. The aim of this study was to examine the location of CER N-(tetracosanoyl)-phytosphingosine (CER NP) in the unit cell of this lamellar phase and compare its position with CER N-(tetracosanoyl)-sphingosine (CER NS). We selected CER NP as it is the most prevalent CER subclass in the human SC, and its location in the LPP is not known. Our neutron diffraction results demonstrate that the acyl chain of CER NP was positioned in the central part of the trilayer structure, with a fraction also present in the outer layers, the same location as determined for the acyl chain of CER NS. In addition, our Fourier transformed infrared spectroscopy results are in agreement with this molecular arrangement, suggesting a linear arrangement for the CER NS and CER NP. These findings provide more detailed insight into the lipid organization in the SC lipid matrix.The microsomal triglyceride transfer protein (MTP) is essential for the secretion of apolipoprotein B (apoB)48- and apoB100-containing lipoproteins in the intestine and liver, respectively. Loss of function mutations in MTP cause abetalipoproteinemia. Heterologous cells are used to evaluate the function of MTP in apoB secretion to avoid background MTP activity in liver and intestine-derived cells. However, these systems are not suitable to study the role of MTP in the secretion of apoB100-containing lipoproteins, as expression of a large apoB100 peptide using plasmids is difficult. Here, we report a new cell culture model amenable for studying the role of different MTP mutations on apoB100 secretion. The endogenous MTTP gene was ablated in human hepatoma Huh-7 cells using single guide RNA and RNA-guided clustered regularly interspaced short palindromic repeats-associated sequence 9 ribonucleoprotein complexes. We successfully established three different clones that did not express any detectable MTTP mRNA or MTP protein or activity. These cells were defective in secreting apoB-containing lipoproteins and accumulated lipids. Furthermore, we show that transfection of these cells with plasmids expressing human MTTP cDNA resulted in the expression of MTP protein, restoration of triglyceride transfer activity, and secretion of apoB100. Thus, these new cells can be valuable tools for studying structure-function of MTP, roles of different missense mutations in various lipid transfer activities of MTP, and their ability to support apoB100 secretion, compensatory changes associated with loss of MTP, and in the identification of novel proteins that may require MTP for their synthesis and secretion.This study aimed to investigate, through in vivo and in vitro methodologies, the effect of acute trans,trans-farnesol (12.5, 25, 50 or 100 mg/kg, p.o.) administration on behavioral and neurochemical parameters associated with pilocarpine-induced epileptic seizure (300 mg/kg, i.p.) in mice. The initial results showed that the compound in question presents no anxiolytic-like or myorelaxant effects, despite reducing locomotor activity in the animals at all doses tested. In addition, the lowest dose increased the latency to onset of the first epileptic seizure, and the time to death. In addition to decreasing the mortality percentage in mice submitted to the pilocarpine model. In this same model, pretreatment with the lowest dose of the compound decreased the hippocampal concentrations of thiobarbituric acid and nitrite, and partially restored striatal concentrations of noradrenaline, dopamine, and serotonin. Taken together, the results suggest that trans,trans-farnesol presents a central depressant effect which contributes to its antiepileptic action which, in turn, seems to be mediated by the antagonism of muscarinic cholinergic receptors, reduction of oxidative stress. and modulation of noradrenaline, dopamine and serotonin concentrations in the central nervous system.Hepatocellular carcinoma (HCC) is one of the most malignant human cancers, with a high mortality rate worldwide. Within an HCC tumor, cancer stem cells (CSCs) are responsible for tumor maintenance and progression and may contribute to resistance to standard HCC treatments. Previously, we characterized CD133+ cells as CSCs in primary HCC and identified chromenopyrimidinone (CPO) as a novel therapeutic for the effective treatment of CD133+ HCC. However, the biological function and molecular mechanism of CD133 remain unclear. Epigenetic alterations of CSCs have impacts on tumor initiation, progression, and therapeutic response. selleck Here, we found that pharmacological and genetic depletion of CD133 in HCC attenuated the activity of DNA methyltransferases via control of DNMT3B stabilization. Genes were ranked by degree of promoter hypo/hyper methylation and significantly differential expression to create an "epigenetically activated by CPO" ranked genes list. Through this epigenetic analysis, we found that CPO treatment altered DNA methylation-mediated oncogenic signaling in HCCs. Specifically, CPO treatment inhibited Adenylyl cyclase-associated protein 1 (CAP1) expression, thereby reducing FAK/ERK activity and EMT-related proteins in HCC. Moreover, CPO improved the efficacy of sorafenib by inhibiting CAP1 expression and FAK/ERK activation in sorafenib-resistant HCC. These novel mechanistic insights may ultimately open up avenues for strategies targeting DNA methylation in liver cancer stem cells and provides novel therapeutic function of CPO for the effective treatment of sorafenib-resistant HCC.

Colon cancer (CC) is a prevalent malignancy worldwide and is one of the most easily altered cancers by dietary regulation. Petunidin 3-O-[rhamnopyranosyl-(trans-p-coumaroyl)]-5-O-(β-D-glucopyranoside) (Pt3R5G) isolated and purified from Lycium ruthenicum Murray, which exhibits highly efficient antioxidant activity and specific anticancer effects, is the flavonoids compound. We aimed to study the effect of Pt3R5G on CC cells and elucidate the potential underlying mechanisms.

Cell proliferation was measured by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and colony formation assays. Cell cycle, cell apoptosis and reactive oxygen species (ROS) analysis were performed by flow cytometry. RNA-sequencing was performed to elucidate the potential underlying mechanisms. The lipid peroxidation level of cells was detected by malondialdehyde (MDA) assay. The mitochondrial morphology of cells was inspected using a transmission electron microscope. Additionally, we overexpressed SLC7A11 to perform rescue experiments. In vivo, xenograft mice assay was performed to verify the effect of Pt3R5G on the growth of colon cancer.

Pt3R5G reduced the cell activity by blocking the cell cycle in G0/G1 phase, inducing the apoptosis and ferroptosis in RKO cells. The overexpressed of SLC7A11, a significantly down-regulated expression gene caused by Pt3R5G, rescued the cell proliferation inhibition and ferroptosis process. Furthermore, Pt3R5G inhibited tumor growth in nude mice. Our study suggests that Pt3R5G inhibits RKO cell proliferation through mainly reducing ferroptosis by down-regulated SLC7A11.

As a potential therapeutic drug, Pt3R5G showed efficient anticancer activity through a variety of pathways.

As a potential therapeutic drug, Pt3R5G showed efficient anticancer activity through a variety of pathways.

Asthma is a chronic inflammatory airway disease associated with the airway narrowing and obstruction. Sinapic acid (SA), a hydroxycinnamic acid, possesses various pharmacological properties including antioxidant and anti-inflammatory activity. This research evaluated effects of different doses of SA on murine model of ovalbumin (OVA)-induced allergic asthma.

Allergic asthma induced by sensitizing mice on days 1 and 14 by intraperitoneal injection of OVA. After initial sensitization, between days 21 and 23, mice were challenged for 30min with an aerosol of 1% (wt/vol) OVA. Treatment with dexamethasone (3mg/kg) or SA (25, 50 or 100mg/kg) were done by oral gavage on days 15-23. Inflammatory cells infiltration and interferon-γ (IFN-γ), interlukin-4 (IL-4), IL-5 and IL-13 levels were evaluated in the bronchoalveolar lavage fluid (BALF). Serum total and OVA-specific immunoglobulin E (IgE) and lung tissue nitric oxide (NO) levels were measured. Histological changes in lung tissue were examined by staining with hematoxylin and eosin (H&E) for cell infiltration, periodic acid-Schiff (PAS) for mucus production and Masson's trichrome for collagen deposition.

Treatment with SA significantly inhibited inflammatory cell infiltration, enhanced IFN-γ level and decreased IL-4, IL-5 and IL-13 levels in BALF. Serum total and OVA-specific IgE levels and NO level in lung tissue were significantly reduced by SA. Histological examination demonstrated that SA significantly attenuated inflammatory cell infiltration and mucus-producing cells in the lung.

These data suggest that SA may be a new therapeutic potential to treat allergic asthma through suppressing T-helper 2 immune responses.

These data suggest that SA may be a new therapeutic potential to treat allergic asthma through suppressing T-helper 2 immune responses.