13,163 results match your criteria manner modulation


Metformin Dysregulates the Unfolded Protein Response and the WNT/β-Catenin Pathway in Endometrial Cancer Cells through an AMPK-Independent Mechanism.

Cells 2021 Apr 30;10(5). Epub 2021 Apr 30.

Department of Medical and Translational Sciences & Institute of Endocrinology and Experimental Oncology of CNR, University "Federico II", 80131 Naples, Italy.

Multiple lines of evidence suggest that metformin, an antidiabetic drug, exerts anti-tumorigenic effects in different types of cancer. Metformin has been reported to affect cancer cells' metabolism and proliferation mainly through the activation of AMP-activated protein kinase (AMPK). Here, we show that metformin inhibits, indeed, endometrial cancer cells' growth and induces apoptosis. Read More

View Article and Full-Text PDF

Donor Treg expansion by liposomal α-galactosylceramide modulates Tfh cells and prevents sclerodermatous chronic graft-versus-host disease.

Immun Inflamm Dis 2021 May 4. Epub 2021 May 4.

Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Background And Aim: Chronic graft-versus-host disease (cGVHD) is a major cause of nonrelapse morbidity and mortality following hematopoietic stem cell transplantation (HSCT). α-Galactosylceramide (α-GC) is a synthetic glycolipid that is recognized by the invariant T-cell receptor of invariant natural killer T (iNKT) cells in a CD1d-restricted manner. Stimulation of iNKT cells by α-GC leads to the production of not only immune-stimulatory cytokines but also immune-regulatory cytokines followed by regulatory T-cell (Treg) expansion in vivo. Read More

View Article and Full-Text PDF

Pharmacological modulation of T cell immunity results in long-term remission of autoimmune arthritis.

Proc Natl Acad Sci U S A 2021 May;118(19)

Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, United Kingdom;

Chronic inflammatory diseases like rheumatoid arthritis are characterized by a deficit in fully functional regulatory T cells. DNA-methylation inhibitors have previously been shown to promote regulatory T cell responses and, in the present study, we evaluated their potential to ameliorate chronic and acute animal models of rheumatoid arthritis. Of the drugs tested, decitabine was the most effective, producing a sustained therapeutic effect that was dependent on indoleamine 2,3-dioxygenase (IDO) and was associated with expansion of induced regulatory T cells, particularly at the site of disease activity. Read More

View Article and Full-Text PDF

GAMYB TF modulates bHLH142 and is homeostatically regulated by TDR TF during rice anther tapetal and pollen development.

J Exp Bot 2021 May 3. Epub 2021 May 3.

Institute of Bioagricultural Science, National Chiayi University, Chiayi, Taiwan.

GAMYB, UDT1, TIP2/bHLH142, TDR, and EAT1/DTD are important transcription factors (TFs) that play a crucial role during rice pollen development. This study demonstrates that bHLH142 acts downstream of UDT1 and GAMYB and works as a "hub" in these two pollen pathways. We show that GAMYB modulates bHLH142 expression through specific binding to the MYB motif of bHLH142 promoter during early stage of pollen development; while TDR acts as a transcriptional repressor of the GAMYB modulation of bHLH142 by binding to the E-box close to the MYB motif on the promoter. Read More

View Article and Full-Text PDF

Succinate Promotes Phagocytosis of Monocytes/Macrophages in Teleost Fish.

Front Mol Biosci 2021 15;8:644957. Epub 2021 Apr 15.

Center for Proteomics and Metabolomics, State Key Laboratory of Biocontrol, Guangdong Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.

Development of immunity-based strategy to manage bacterial infection is urgently needed in aquaculture due to the widespread of antibiotic-resistant bacteria. Phagocytosis serves as the first line defense in innate immunity that engulfs bacteria and restricts their proliferations and invasions. However, the mechanism underlying the regulation of phagocytosis is not fully elucidated and the way to boost phagocytosis is not yet explored. Read More

View Article and Full-Text PDF

Inhibition of p53/miR-34a/SIRT1 axis ameliorates podocyte injury in diabetic nephropathy.

Biochem Biophys Res Commun 2021 Apr 28;559:48-55. Epub 2021 Apr 28.

Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China; Kidney and Dialysis Institute of Shanghai, Shanghai, China; Kidney and Blood Purification Laboratory of Shanghai, Shanghai, China. Electronic address:

Podocyte injury is associated with albuminuria and the progression of diabetic nephropathy (DN). MiR-34a, a p53-regulated miRNA, directly targets SIRT1 and contributed to DN progression. MiR-34a represses SIRT1 to activate p53 and establish a positive feedback loop. Read More

View Article and Full-Text PDF

Attention reduces the burstiness of V1 neurons involved in attended target enhancement.

Eur J Neurosci 2021 May 1. Epub 2021 May 1.

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.

Attention-dependent reduction in the tendency for neurons to fire bursts (burstiness) is widely observed in the visual cortex. However, the underlying mechanism and the functional role of this phenomenon remain unclear. We recorded well-isolated single-unit activities in primary visual cortex (V1) from two primates (Macaca mulatta) while they performed a detection task engaging spatial attention with two levels of difficulty (hard/easy). Read More

View Article and Full-Text PDF

Suppression of lysosomal acid alpha-glucosidase impacts the modulation of transcription factor EB translocation in pancreatic cancer.

Cancer Sci 2021 May 1. Epub 2021 May 1.

Department of Surgery, Jikei University School of Medicine, Tokyo, Japan.

Lysosomal degradation plays a crucial role in the metabolism of biological macromolecules supplied by autophagy. The regulation of the autophagy-lysosome system, which contributes to intracellular homeostasis, chemoresistance, and tumor progression, has recently been revealed as a promising therapeutic approach for pancreatic cancer (PC). However, the details of lysosomal catabolic function in PC cells have not been fully elucidated. Read More

View Article and Full-Text PDF

Spectral composition of artificial illuminants and their effect on eye growth in chicks.

Exp Eye Res 2021 Apr 27:108602. Epub 2021 Apr 27.

New England College of Optometry, Department of Biomedical Science and Disease, Boston, MA, United States. Electronic address:

In broadband light, longitudinal chromatic aberration (LCA) provides emmetropization signals from both wavelength defocus and the resulting chromatic cues. Indoor illuminants vary in their spectral output, potentially limiting the signals from LCA. Our aim is to investigate the effect that artificial illuminants with different spectral outputs have on chick emmetropization with and without low temporal frequency modulation. Read More

View Article and Full-Text PDF

A Study to Enhance the Oral Bioavailability of S-Adenosyl-L-Methionine (SAME): SLN and SLN Nanocomposite Particles.

Chem Phys Lipids 2021 Apr 27:105086. Epub 2021 Apr 27.

Ankara University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 06560, Ankara, Turkey. Electronic address:

The endogenous molecule, S-adenosyl-L-methionine (SAMe) is a key factor due to its role in the methylation cycle and modulation of monoaminergic neurotransmission. Since many mental disorders have linked to the monoaminergic system, the level of SAMe in blood and cerebrospinal fluid is important in the treatment of major depression. In this study, solid lipid nanoparticles (SLN) were prepared in order to increase the limited oral bioavailability of SAMe, and SLN based nanocomposite particles (SAMe-SLN-NC) were further developed using an enteric polymer for passive targeting of intestinal lymphatic system. Read More

View Article and Full-Text PDF

VEGF Contributes to Mesenchymal Stem Cell-Mediated Reversion of Nor1-Dependent Hypertrophy in iPS Cell-Derived Cardiomyocytes.

Stem Cells Int 2021 10;2021:8888575. Epub 2021 Apr 10.

Department of Cardiothoracic Surgery, Heart Center of the University of Cologne, Cologne, Germany.

Myocardial hypertrophy is present in many heart diseases, representing a strong predictor of adverse cardiovascular outcomes. Regarding therapeutic intervention, mesenchymal stem cells (MSCs) have been suggested to significantly reduce cardiac hypertrophy and progression to heart failure. Preconditioning of MSCs was previously demonstrated to highly improve their paracrine activity resulting in modulation of immune responses and the progression of diseases. Read More

View Article and Full-Text PDF

S-Nitrosylation in Tumor Microenvironment.

Int J Mol Sci 2021 Apr 27;22(9). Epub 2021 Apr 27.

Department of Cancer Biology, University of Toledo Health Science Campus, 3000 Arlington Ave., Toledo, OH 43614, USA.

S-nitrosylation is a selective and reversible post-translational modification of protein thiols by nitric oxide (NO), which is a bioactive signaling molecule, to exert a variety of effects. These effects include the modulation of protein conformation, activity, stability, and protein-protein interactions. S-nitrosylation plays a central role in propagating NO signals within a cell, tissue, and tissue microenvironment, as the nitrosyl moiety can rapidly be transferred from one protein to another upon contact. Read More

View Article and Full-Text PDF

GSK-3α Inhibition in Drug-Resistant CML Cells Promotes Susceptibility to NK Cell-Mediated Lysis in an NKG2D- and NKp30-Dependent Manner.

Cancers (Basel) 2021 Apr 9;13(8). Epub 2021 Apr 9.

Department of Biomedical Sciences, Microbiology, University of Ulsan College of Medicine, Seoul 05505, Korea.

Natural killer (NK) cells are innate cytotoxic lymphocytes that provide early protection against cancer. NK cell cytotoxicity against cancer cells is triggered by multiple activating receptors that recognize specific ligands expressed on target cells. We previously demonstrated that glycogen synthase kinase (GSK)-3β, but not GSK-3α, is a negative regulator of NK cell functions via diverse activating receptors, including NKG2D and NKp30. Read More

View Article and Full-Text PDF

Furin Prodomain ppFurin Enhances Ca Entry Through Orai and TRPC6 Channels' Activation in Breast Cancer Cells.

Cancers (Basel) 2021 Apr 1;13(7). Epub 2021 Apr 1.

LAMC, INSERM, University Bordeaux, U1029, F-33600 Pessac, France.

The intracellular calcium concentration ([Ca]) modulation plays a key role in the regulation of cellular growth and survival in normal cells and failure of [Ca] homeostasis is involved in tumor initiation and progression. Here we showed that inhibition of Furin by its naturally occurring inhibitor the prodomain ppFurin in the MDA-MB-231 breast cancer cells resulted in enhanced store-operated calcium entry (SOCE) and reduced the cell malignant phenotype. Expression of ppFurin in a stable manner in MDA-MB-231 and the melanoma MDA-MB-435 cell lines inhibits Furin activity as assessed by in vitro digestion assays. Read More

View Article and Full-Text PDF

Epinephrine Modulates Memory of Latent Learning in an Inhibitory Avoidance Task.

Neurobiol Learn Mem 2021 Apr 26:107447. Epub 2021 Apr 26.

Department of Psychology, National Cheng-Kung University.

The present study examined the memory modulatory effect of epinephrine on latent learning of an inhibitory avoidance task. Male Sprague-Dawley rats on the first day were subjected to one of three conditions (no, short or long) in pre-exposure to the task apparatus. One day or several days later, they received the typical inhibitory avoidance training with a 0. Read More

View Article and Full-Text PDF

Triptolide Modulates the Expression of Inflammation-Associated lncRNA-PACER and lincRNA-p21 in -Infected Monocyte-Derived Macrophages.

Front Pharmacol 2021 12;12:618462. Epub 2021 Apr 12.

International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Cape Town, South Africa.

Triptolide is a diterpene triepoxide, which performs its biological activities mechanisms including induction of apoptosis, targeting of pro-inflammatory cytokines, and reshaping of the epigenetic landscape of target cells. However, the targeting of long non-coding RNAs (lncRNAs) by triptolide has not yet been investigated, despite their emerging roles as key epigenetic regulators of inflammation and immune cell function during (Mtb) infection. Hence, we investigated whether triptolide targets inflammation-associated lncRNA-PACER and lincRNA-p21 and how this targeting associates with Mtb killing within monocyte-derived macrophages (MDMs). Read More

View Article and Full-Text PDF

Nanozyme-Powered Giant Unilamellar Vesicles for Mimicry and Modulation of Intracellular Oxidative Stress.

ACS Appl Mater Interfaces 2021 Apr 28. Epub 2021 Apr 28.

Key Laboratory of Bioactive Materials for the Ministry of Education, College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China.

The bottom-up construction of enzyme-based artificial cells is generating increasing interest, but achieving artificial cells for "all artificial modules" remains challenging in synthetic biology. Here, we introduce a fully synthetic cell system by integration of biomimetic nanozymes into giant unilamellar vesicles (GUVs). To mimic native peroxidase for free radical generation by taking advantage of Fenton catalysis reactions, we designed and prepared a de novo artificial nanozyme composed of ferritin heavy-chain scaffold protein and catalytic FeO nanoparticles as the active center. Read More

View Article and Full-Text PDF

Role of aryl hydrocarbon receptor in central nervous system tumors: Biological and therapeutic implications.

Oncol Lett 2021 Jun 11;21(6):460. Epub 2021 Apr 11.

Laboratorio de Investigación en Patología Experimental, Hospital Infantil de México Federico Gómez, Mexico City 06720, México.

Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, whose canonical pathway mainly regulates the genes involved in xenobiotic metabolism. However, it can also regulate several responses in a non-canonical manner, such as proliferation, differentiation, cell death and cell adhesion. AhR plays an important role in central nervous system tumors, as it can regulate several cellular responses via different pathways. Read More

View Article and Full-Text PDF

Developments in Understanding Diffuse Noxious Inhibitory Controls: Pharmacological Evidence from Pre-Clinical Research.

J Pain Res 2021 20;14:1083-1095. Epub 2021 Apr 20.

Central Modulation of Pain Group, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE1 1UL., UK.

Bulbospinal pathways regulate nociceptive processing, and inhibitory modulation of nociception can be achieved via the activity of diffuse noxious inhibitory controls (DNIC), a unique descending pathway activated upon application of a conditioning stimulus (CS). Numerous studies have investigated the effects of varied pharmacological systems on the expression status of a) DNIC (as measured in anaesthetised animals) and b) the descending control of nociception (DCN), a surrogate measure of DNIC-like effects in conscious animals. However, the complexity of the underlying circuitry that governs initiation of a top-down inhibitory response in reaction to a CS, coupled with the methodological limitations associated with using pharmacological tools for its study, has often obscured the exact role(s) of a given drug. Read More

View Article and Full-Text PDF

Lipocalin 2 modulates dendritic cell activity and shapes immunity to influenza in a microbiome dependent manner.

PLoS Pathog 2021 Apr 27;17(4):e1009487. Epub 2021 Apr 27.

Research Laboratory of Infection Biology, Department of Medicine I, Medical University of Vienna, Austria.

Lipocalin 2 (LCN2) is a secreted glycoprotein with roles in multiple biological processes. It contributes to host defense by interference with bacterial iron uptake and exerts immunomodulatory functions in various diseases. Here, we aimed to characterize the function of LCN2 in lung macrophages and dendritic cells (DCs) using Lcn2-/- mice. Read More

View Article and Full-Text PDF

Comparison of wide-band vibrotactile and friction modulation surface gratings.

IEEE Trans Haptics 2021 Apr 27;PP. Epub 2021 Apr 27.

This study seeks to understand conditions under which virtual gratings produced via vibrotaction and friction modulation are perceived as similar and to find physical origins in the results. To accomplish this, we developed two single-axis devices, one based on electroadhesion and one based on out-of-plane vibration. The two devices had identical touch surfaces, and the vibrotactile device used a novel closed-loop controller to achieve precise control of out-of-plane plate displacement under varying load conditions across a wide range of frequencies. Read More

View Article and Full-Text PDF

Differential regulation of autophagy by STAU1 in alveolar rhabdomyosarcoma and non-transformed skeletal muscle cells.

Cell Oncol (Dordr) 2021 Apr 26. Epub 2021 Apr 26.

Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, K1H 8M5, Canada.

Purpose: Recent work has highlighted the therapeutic potential of targeting autophagy to modulate cell survival in a variety of diseases including cancer. Recently, we found that the RNA-binding protein Staufen1 (STAU1) is highly expressed in alveolar rhabdomyosarcoma (ARMS) and that this abnormal expression promotes tumorigenesis. Here, we asked whether STAU1 is involved in the regulation of autophagy in ARMS cells. Read More

View Article and Full-Text PDF

Exercise-Induced Modulation of Angiotensin II Responses in Femoral Veins From 2-Kidney-1-Clip Hypertensive Rats.

Front Physiol 2021 7;12:620438. Epub 2021 Apr 7.

Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, LA, United States.

The present study investigated the angiotensin II (Ang II) responses in rat femoral veins taken from 2-kidney-1clip (2K1C) hypertensive rats at 4 weeks after clipping, as well as the effects of exercise on these responses. In this manner, femoral veins taken from 2K1C rats kept at rest or exposed to acute exercise or to exercise training were challenged with Ang II or endothelin-1 (ET-1) in organ bath. Simultaneously, the presence of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were determined in these preparations by western blotting. Read More

View Article and Full-Text PDF

Propofol enhanced the cell sensitivity to paclitaxel (PTX) in prostatic cancer (PC) through modulation of HOTAIR.

Genes Genomics 2021 Apr 23. Epub 2021 Apr 23.

Department of Anesthesiology, West China Hospital, Sichuan University, No. 38, Guoxue Ave, Wuhou, Chengdu, Sichuan, 610041, China.

Background: PTX is widely used in cancer treatments.

Objective: In this paper, we explored the role and potential molecular mechanism of propofol in regulating PTX sensitivity in PC cells.

Methods: Prostatic cancer cell line PC3 was treated using different concentrations of PTX (10 nM, 50 nM), propofol (150 μM, 300 μM) or transfected with overexpressed HOTAIR plasmid. Read More

View Article and Full-Text PDF

Auxiliary subunits of the AMPA: The Shisa family of proteins.

Curr Opin Pharmacol 2021 Apr 20;58:52-61. Epub 2021 Apr 20.

Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Faculty of Science, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. Electronic address:

AMPA receptors mediate fast synaptic transmission in the CNS and can assemble with several types of auxiliary proteins in a spatio-temporal manner, from newly synthesized AMPA receptor tetramers to mature AMPA receptors in the cell membrane. As such, the interaction of auxiliary subunits with the AMPA receptor plays a major role in the regulation of AMPA receptor biogenesis, trafficking, and biophysical properties. Throughout the years, various 'families' of proteins have been identified and today the approximate full complement of AMPAR auxiliary proteins is known. Read More

View Article and Full-Text PDF

E. coli RNase I exhibits a strong Ca2+-dependent inherent double-stranded RNase activity.

Nucleic Acids Res 2021 Apr 22. Epub 2021 Apr 22.

New England Biolabs, Inc., 240 County Road, Ipswich, MA 01938, USA.

Since its initial characterization, Escherichia coli RNase I has been described as a single-strand specific RNA endonuclease that cleaves its substrate in a largely sequence independent manner. Here, we describe a strong calcium (Ca2+)-dependent activity of RNase I on double-stranded RNA (dsRNA), and a Ca2+-dependent novel hybridase activity, digesting the RNA strand in a DNA:RNA hybrid. Surprisingly, Ca2+ does not affect the activity of RNase I on single stranded RNA (ssRNA), suggesting a specific role for Ca2+ in the modulation of RNase I activity. Read More

View Article and Full-Text PDF

HucMSC exosome-delivered 14-3-3ζ alleviates ultraviolet radiation-induced photodamage via SIRT1 pathway modulation.

Aging (Albany NY) 2021 Apr 21;13. Epub 2021 Apr 21.

Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, People’s Republic of China.

Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-ex) are nano-sized membrane-bound vesicles that have been reported to facilitate skin regeneration and repair. However, the roles played by hucMSC-ex in ultraviolet (UV) radiation-induced skin photodamage and the underlying mechanisms remain unknown. To investigate the functions of hucMSC-ex in a rat model of acute skin photodamage, immunofluorescence and immunohistochemical staining, quantitative real-time-polymerase chain reaction (qRT-PCR), western blot, and gene silencing assays were performed. Read More

View Article and Full-Text PDF

GDC-0326 Enhances the Effects of 5-Fu in Colorectal Cancer Cells by Inducing Necroptotic Death.

Onco Targets Ther 2021 13;14:2519-2530. Epub 2021 Apr 13.

Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310020, People's Republic of China.

Aim: Chemoresistance to 5-fluorouracil (5-Fu) is common in colorectal cancer (CRC). Programmed necrosis (necroptosis) is an alternative form of programmed cell death regulated by receptor-interacting protein kinase (RIPK) 1 and 3, assumed as a novel target of cancer therapy. In this study, we aimed to explore whether a novel small molecular agent GDC-0326 could facilitate the effect of 5-Fu through necroptosis. Read More

View Article and Full-Text PDF

Nutrient supplements from selected botanicals mediated immune modulation of the tumor microenvironment and antitumor mechanism.

Cancer Immunol Immunother 2021 Apr 20. Epub 2021 Apr 20.

Department of Oncological Sciences, Icahn School of Medicine At Mount Sinai, New York, 10029, USA.

Specific extracts of selected vegetables (SV) have been shown to benefit the survival of stage IIIb/IV non-small cell lung cancer patients in phase I/II studies and is currently in a phase III trial. However, the underlying mechanism of SV-mediated antitumor immune responses has not been elucidated. Our results indicate that SV modulated the NK and adoptive T cell immune responses in antitumor efficacy. Read More

View Article and Full-Text PDF

Modulation of proteasome activity by curcumin and didemethylcurcumin.

J Biomol Struct Dyn 2021 Apr 20:1-8. Epub 2021 Apr 20.

Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA.

Modulation of proteasome function by pharmacological interventions and molecular biology tools is an active area of research in cancer biology and neurodegenerative diseases. Curcumin (diferuloylmethane) is a naturally occurring polyphenol that affects multiple signaling pathways. Curcumin shows anti-inflammatory, antioxidant, anti-angiogenic, or anti-apoptotic properties. Read More

View Article and Full-Text PDF