Transcription initiation of human Oct-1 transcription factor-encoding gene involves two promoters, 1U and 1L, located at a substantial distance (about 100 kb) apart. The structure of these promoters and the adjacent sequences is different. Specifically, the 1U sequence is GC-rich, while the 1L sequence is AT-rich. Correspondingly, more than 25 GC-rich Sp1 cis-elements were localized within the 1U region, while in the 1L sequence nearly equal amount of homeo-specific NTAATNN sites along with two ATGCAAAT octamers were found. Analysis of transfection of recombinant plasmids, carrying the promoter fragments with or without enhancer indicated that expression from the 1L promoter was tissue-specific. In nonlymphoid HEK293 cells efficiency of transcription from the 1U promoter was several times higher than that from the 1L promoter. Another expression pattern was observed at transfection of the same constructs into Raji lymphoid cells. In this case the level of transcription from the L promoter (fragment L2) at the presence of external enhancer was higher than that from the fragments containing the 1U promoter. It was shown that the distal regions of 1U and 1L were capable of silencing activity. In Raji cells enhancer completely overcomes the activity of U silencer, but only partly overcomes the activity of L silencer. Our data on the interaction of two promoters with the enhancer and silencer in different cell types point to fine tissue-specific regulation of the oct-1 gene expression, especially in lymphatic cells.
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Naunyn Schmiedebergs Arch Pharmacol
December 2024
Internal Medicine IX - Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University, Medical Faculty Heidelberg, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
Zosuquidar (LY335979) is a widely used experimental P-glycoprotein (P-gp) inhibitor, which is commended as very potent but also as very specific for P-gp. In this in vitro and in silico study, we demonstrated for the first time that zosuquidar also inhibits organic cation transporters (OCT) 1-3, albeit less potently than P-gp. This still has to be kept in mind when zosuquidar is used to inhibit cellular efflux of P-gp substrates that are concurrently transported into the cells by OCTs.
View Article and Find Full Text PDFLancet Glob Health
January 2025
Institute for Global Health and Development, Aga Khan University, Karachi, Pakistan; Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON, Canada.
Background: Infectious diseases remain the leading cause of death among children younger than 5 years due to disparities in access and acceptance of essential interventions. The Community Mobilisation and Community Incentivisation (CoMIC) trial was designed to evaluate a customised community mobilisation and incentivisation strategy for improving coverage of evidence-based interventions for child health in Pakistan.
Methods: CoMIC was a three-arm cluster-randomised, controlled trial in rural areas of Pakistan.
J Bodyw Mov Ther
October 2024
Faculty of Health Sciences, Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.
Objectives: The aim of this systematic review update was to determine the average effect of massage for adults with neck pain (NP) contrasted against another standard treatment.
Methods: Randomised controlled trials comparing massage to standard treatments were included; placebo/no treatment comparisons were excluded. Databases were searched (CENTRAL, MEDLINE, EMBASE, CINAHL, ICL, trial registries) from inception to Oct-1-2023.
Curr Issues Mol Biol
November 2024
Department of Biological Science, Faculty of Science, Kuwait University, Kuwait City 13060, Kuwait.
Lipoprotein lipase (LPL) is a multifunctional protein that catalyzes the hydrolysis of plasma triglycerides, releasing free fatty acids, which play critical roles in the metabolism and transport of lipids. The transcription of in response to cell types and regulatory factors is a complex process that starts with its promoter. In previous studies, several proximal regulatory elements within the human promoter were individually characterized.
View Article and Find Full Text PDFEur J Drug Metab Pharmacokinet
November 2024
Changsha Research and Development Center on Obstetric and Gynecologic Traditional Chinese Medicine Preparation, NHC Key Laboratory of Birth Defects Research, Prevention and Treatment, Hunan Provincial Maternal and Child Health Care Hospital, No. 53 Xiangchun Road, Kaifu District, Changsha, 410008, Hunan, China.
Background And Objectives: Hypertensive nephropathy (HN) has become one of the main causes of end-stage renal disease. Drug combination therapy is a common clinical treatment for HN. However, the impact of HN on drug-metabolizing enzymes and transporters, which may lead to drug-drug interactions (DDIs) and even trigger toxic side effects, remains unclear.
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