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Specific activation of hypoxia-inducible factor-2 α by propionate metabolism via a β-oxidation-like pathway stimulates MUC2 production in intestinal goblet cells
In this study, we investigated the mechanism of MUC2 expression by propionate, an SCFA, in intestinal goblet cells. The real time oxygen consumption rate (OCR) and ATPase activity were measured to investigate the induction of hypoxia by propionate. Using 2-dimensional electrophoresis (2-DE), microarray analysis, and siRNA-induced gene silencing, we found that propionate is metabolized via a β-oxidation-like pathway instead of the vitamin B12-dependent carboxylation pathway (also known as the methylmalonyl pathway). We verified the results by analyzing several intermediates in the pathway using LC-MS and GC-MS. Propionate ...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - September 12, 2022 Category: Drugs & Pharmacology Authors: Seongho Ma Jiah Yeom Young-Hee Lim Source Type: research

Menaquinone-7 protects astrocytes by regulating mitochondrial function and inflammatory response under hypoxic conditions.
CONCLUSIONS: Our study is the first to confirm that MK-7 can protect astrocytes from hypoxia-induced cytotoxicity, possibly by inhibiting mitochondrial dysfunction and the expression of proinflammatory cytokines. Gas6 may also participate in these protective effects. PMID: 33090426 [PubMed - as supplied by publisher]
Source: European Review for Medical and Pharmacological Sciences - October 23, 2020 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

Antifibrotic action of Yifei Sanjie formula enhanced autophagy via PI3K-AKT-mTOR signaling pathway in mouse model of pulmonary fibrosis
Publication date: October 2019Source: Biomedicine & Pharmacotherapy, Volume 118Author(s): Jing-Ze Yu, Yi Ying, Yang Liu, Chun-Bin Sun, Chen Dai, Shan Zhao, Shou-Zheng Tian, Jing Peng, Ni-Ping Han, Jia-Li Yuan, Jin-Yuan Yan, Zhong-Shan YangAbstractPulmonary fibrosis (PF) is a crippling disease characterized by progressive dyspnea and associated with a high mortality rate, but its origin is unknown and there is no effective treatment. Yifei Sanjie formula (YFSJF) is a Chinese medicine that is widely used for treatment of respiratory systems disease. However, the molecular basis for the function of YFSJF has not been determin...
Source: Biomedicine and Pharmacotherapy - August 9, 2019 Category: Drugs & Pharmacology Source Type: research

Current Development of siRNA Bioconjugates: From Research to the Clinic
In this study, it was shown that the main factor determining the nature of the biodistribution of conjugates is their lipophilicity. Conjugates of siRNA with lower lipophilicity; i.e., derivatives of retinoic acid, lithocholic acid, and docosahexanoic acid with greater efficiency than cholesterol conjugates accumulated in the kidneys, bladder, and lungs of the mouse after subcutaneous injection (Biscans et al., 2018). This fact is consistent with previous data that showed that more lipophilic conjugates bind more efficiently to serum components, and thus are not excreted by the kidneys (Wolfrum et al., 2007; Osborn et al.,...
Source: Frontiers in Pharmacology - April 25, 2019 Category: Drugs & Pharmacology Source Type: research

Plant-Derived Alkaloids: The Promising Disease-Modifying Agents for Inflammatory Bowel Disease
Conclusion This paper summarizes the current findings regarding the anti-colitis activity of plant-derived alkaloids and shows how these alkaloids exhibit significant and beneficial effects in alleviating colonic inflammation. These natural alkaloids are not only promising agents for IBD treatment but are also components for developing new wonder drugs. However, the underlying molecular mechanisms or toxicological evaluation of most plant-derived alkaloids still require much scientific research, and their actual efficacies for IBD patients have not been verified well in field research. Thus, further clinical trials to elu...
Source: Frontiers in Pharmacology - April 11, 2019 Category: Drugs & Pharmacology Source Type: research

Vitamin D receptor regulates high-level glucose induced retinal ganglion cell damage through STAT3 pathway.
CONCLUSIONS: Inhibition of VDR exerts a protective role in high-level glucose induced RGCs damage by activating the STAT3 pathway. PMID: 30468500 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - November 24, 2018 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

Homocysteine induced oxidative stress in human umbilical vein endothelial cells via regulating methylation of SORBS1.
CONCLUSIONS: We indicated that Hcy induced oxidative stress in HUVECs via regulating methylation of SORBS1. We also found that Fc and B12 treatment attenuated the oxidative stress and inflammation induced by Hcy in HUVECs. The findings indicated that Fc and B12 might be effective agents for the treatment of Hcy induced AS. PMID: 30402861 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - November 9, 2018 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

Inhibition of BMP4 and Alpha Smooth Muscle Actin Expression in LX-2 Hepatic Stellate Cells by BMP4-siRNA Lipid Based Nanoparticle.
Conclusion: VA-coated liposomes were successfully designed to deliver BMP4-siRNA to specifically target HSC. The novel delivery system discussed herein may serve as a potential therapeutic strategy for the treatment of liver fibrosis in the future. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page. PMID: 29578859 [PubMed - in process]
Source: J Pharm Pharm Sci - March 28, 2018 Category: Drugs & Pharmacology Authors: Omar R, Yang J, Alrushaid S, Burczynski FJ, Minuk GY, Gong Y Tags: J Pharm Pharm Sci Source Type: research

Effects of Ascorbyl-2-phosphate Magnesium on Human Keratinocyte Toxicity and Pathological Changes by Sorafenib.
Abstract Hand-foot skin reaction is recognized as one of the most common adverse events related to multiple tyrosine kinase inhibitors, but an effective prevention method has not been identified. The chief aim of this study was to find a mechanism-based preventive method for the skin toxicity induced by sorafenib using vitamin C derivatives. The effects of ascorbyl-2-phosphate magnesium (P-VC-Mg) on the molecular and pathological changes induced by sorafenib were investigated in human keratinocyte HaCaT cells. The cell growth inhibition and apoptotic effects of sorafenib were attenuated by P-VC-Mg. Moreover, P-VC-...
Source: Biological and Pharmaceutical Bulletin - September 6, 2017 Category: Drugs & Pharmacology Authors: Yamamoto K, Shichiri H, Ishida T, Kaku K, Nishioka T, Kume M, Makimoto H, Nakagawa T, Hirano T, Bito T, Nishigori C, Yano I, Hirai M Tags: Biol Pharm Bull Source Type: research

Vitamin E promotes breast cancer cell proliferation by reducing ROS production and p53 expression.
CONCLUSIONS: Vitamin E accelerated breast cancer growth by reducing ROS production and p53 expression. PMID: 27383327 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - July 9, 2016 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

New Preparative Approaches for Micro and Nano Drug Delivery Carriers.
Abstract The full success of pharmacological therapies is strongly depending from the use of suitable, efficient and smart drug delivery systems (DDSs). Thus DDSs development is one of the main challenges in pharmaceutical industry both to achieve tailored carrier systems based on drug features and to promote manufacturing innovations to reduce energetic resources, emissions, wastes and risks. Main functions of an ideal DDS are: to protect loaded active molecules from degradation in physiological environments; to deliver them in a controlled manner and towards a specific organ or tissue, to allow the maintenance o...
Source: Current Drug Delivery - June 26, 2016 Category: Drugs & Pharmacology Authors: Lamberti G, Barba AA, Bochicchio S, Dalmoro A, d'Amore M Tags: Curr Drug Deliv Source Type: research

Overexpression of uncoupling protein-2 in cancer: metabolic and heat changes, inhibition and effects on drug resistance
Abstract This paper deals with the role of uncoupling protein-2 (UCP2) in cancer. UCP2 is overexpressed in cancer. This overexpression results in uncoupling of mitochondrial oxidative phosphorylation and a shift in production of ATP from mitochondrial oxidative phosphorylation to cytosolic aerobic glycolysis. UCP2 overexpression results in the following changes. Mitochondrial membrane potential (Δψ m) is decreased and lactate accumulates. There is a diminished production of reactive oxygen species and apoptosis is inhibited post-exposure to chemotherapeutic agents. There is an increase in heat and ...
Source: Inflammopharmacology - November 5, 2015 Category: Drugs & Pharmacology Source Type: research

Vitamin D Receptor-Mediated Upregulation of CYP3A4 and MDR1 by Quercetin in Caco-2 cells
Planta MedDOI: 10.1055/s-0035-1557898To examine whether quercetin interacts with vitamin D receptor, we investigated the effects of quercetin on vitamin D receptor activity in human intestinal Caco-2 cells. The effects of quercetin on the expression of the vitamin D receptor target genes, vitamin D3 24-hydroxylase, cytochrome P450 3A4, multidrug resistance protein 1, and transient receptor potential vanilloid type 6 were measured using quantitative polymerase chain reaction. The vitamin D receptor siRNA was used to assess the involvement of the vitamin D receptor. Vitamin D receptor activation using a vitamin D responsive ...
Source: Planta Medica - September 14, 2015 Category: Drugs & Pharmacology Authors: Chae, Yoon-JeeCho, Kwan HyungYoon, In-SooNoh, Chi-KyoungLee, Hyo-JongPark, YohanJi, EunheeSeo, Min-DukMaeng, Han-Joo Tags: Original Papers Source Type: research

Anti-melanogenic effects of δ-tocotrienol are associated with tyrosinase-related proteins and MAPK signaling pathway in B16 melanoma cells
This study aimed to elucidate the mechanism involved in the anti-melanogenic effects of δ-tocotrienol (δT3) in B16 melanoma cells. Results showed that at 20μM of δT3 significantly inhibited melanin formation and ROS generation. Treatment with δT3 also effectively suppressed the expression of melanogenesis-related proteins, including MC1R, MITF, TYRP-1, and TYRP-2. More importantly, we observed that the mitogen-activated protein kinase (MAPK) pathway was involved in mediating δT3's inhibitory effect against melanin production. Specifically, δT3 treatment markedly induced the activation of extracellular signal-regulat...
Source: Phytomedicine - March 27, 2014 Category: Drugs & Pharmacology Authors: Lean-Teik Ng, Liang-Tzung Lin, Chiu-Lan Chen, Hsiu-Wen Chen, Shu-Jing Wu, Chun-Ching Lin Tags: Oncology and Hematology Source Type: research

Differential regulation of drug transporter expression by all-trans retinoic acid in hepatoma HepaRG cells and human hepatocytes.
Abstract All-trans retinoic acid (atRA) is the active form of vitamin A, known to activate retinoid receptors, especially the heterodimer retinoid X receptor (RXR):retinoic acid receptor (RAR) that otherwise may play a role in regulation of some drug transporters. The present study was designed to characterize the nature of human hepatic transporters that may be targeted by atRA and the heterodimer RXR:RAR. Exposure of human hepatoma HepaRG cells and primary human hepatocytes to 5 μM atRA down-regulated mRNA levels of various sinusoidal solute carrier (SLC) influx transporters, including organic anion transportin...
Source: European Journal of Pharmaceutical Sciences - January 22, 2013 Category: Drugs & Pharmacology Authors: Le Vee M, Jouan E, Stieger B, Fardel O Tags: Eur J Pharm Sci Source Type: research