Intramural By Sanya Mehta, Victoria Placentra, Saniya Rattan, Nancy Urbano, Qing Xu
Researchers in the Division of the National Toxicology Program (DNTP) examined the long-term use of hydroxyurea (HU) therapy, the most effective strategy for managing sickle cell anemia, a genetic disorder of the blood. HU effectively increases healthy fetal hemoglobin production, but through a mechanism that is harmful to cells. The use of HU and its adverse side-effects are well-managed in adults. However, the U.S. Food and Drug Administration only recently approved HU for use in children and data is limited for understanding the impact the drug may have on child development.
The scientists conducted critical preliminary studies to identify appropriate doses for evaluating long-term effects. They assessed HU kinetics, or the movement of the chemical in the body, during critical periods of rodent development. HU was administered to pregnant rats from late gestation through lactation and to their offspring for 34 days after birth. Decreased body weight and adverse clinical observations, such as hair loss, appeared in offspring receiving at least 75 milligrams per kilogram per day. Data revealed gestational transfer of HU, but minimal lactational transfer. There was no difference in the half-life of HU between age and sex, but systemic exposure decreased with increasing age. (SM)
Citation:Huang MC, Turner KJ, Vallant M, Robinson VG, Lu Y, Price CJ, Fennell TR, Silinski MA, Waidyanatha S, Ryan KR, Black SR, Fernando RA, McIntyre BS. 2020. Tolerability and age-dependent toxicokinetics following perinatal hydroxyurea treatment in Sprague Dawley rats. J Appl Toxicol; doi:10.1002/jat.4087 [Online 25 November 2020].
Individual heterogeneity, or genetic variability, can substantially affect reprogramming of somatic cells into induced pluripotent stem cells (iPSCs), according to NIEHS scientists and their collaborators. iPSCs are stem cells that are derived from differentiated cells, such as fibroblasts, and they can both self-renew and are pluripotent, meaning they can be differentiated into other cell-types. In a previous publication, the research team obtained fibroblasts tissue cells from healthy, diverse donors and observed that each persons fibroblasts had consistent differences in the ability to be reprogrammed to iPSCs. Ancestry was identified as a large contributing factor. In this publication, the research team identified genes and pathways that may be responsible for the observed differences.
Using 72 dermal fibroblast-iPSCs from self-identified African Americans and white Americans, the researchers found ancestry-dependent and ancestry-independent genes associated with reprogramming efficiency. These include genes involved in intracellular transport regulation, protein localization, and cytoskeletal organization, as well as dynamic biological processes like cancer and wound healing. The findings suggest that the heterogeneity of an individual can influence iPSC reprogramming, and the scientists suggested that these genes will provide insights into ancestry-dependent regulation of cell fate and reprogramming. (NU)
Citation:Bisogno LS, Yang J, Bennett BD, Ward JM, Mackey LC, Annab LA, Bushel PR, Singhal S, Schurman SH, Byun JS, Napoles AM, Perez-Stable EJ, Fargo DC, Gardner K, Archer TK. 2020. Ancestry-dependent gene expression correlates with reprogramming to pluripotency and multiple dynamic biological processes. Sci Adv 6(47):eabc3851.
NIEHS researchers and their collaborators have developed tools to deliver diphosphoinositol polyphosphates (PP-InsPs) into cultured cells to study their actions. The PP-InsPs are multipurpose cell signaling molecules that regulate diverse biological processes. The few tools that exist to study PP-InsP activities in living cells require hours-long procedures and are plagued by the possibility of off-target effects, thereby compromising short-term studies.
Because the PP-InsPs are highly charged, they cannot enter cells. Therefore, the researchers masked the charge by encapsulating the PP-InsPs inside liposomes. These are minute spherical sacs of phospholipid molecules are similar to those found in cell membranes, except that the researchers used phospholipids that melt at 40 degrees Celsius (i.e., fractionally above body temperature). The liposomes also contain a dye that warms when exposed to biologically harmless red light. These liposomes are readily accumulated by the cells. Finally, the cells are briefly placed under red light for two to five minutes, causing the liposomes to heat, melt, and release their PP-InsP cargo.
To validate this new delivery method, the scientists developed a fluorescent PP-InsP analogue and monitored its release into cells. This new intracellular PP-InsP delivery method is adjustable and applicable to all PP-InsPs and analogs. (SR)
Citation:Wang Z, Jork N, Bittner T, Wang H, Jessen HJ, Shears SB. 2020. Rapid stimulation of cellular Pi uptake by the inositol pyrophosphate InsP8 induced by its photothermal release from lipid nanocarriers using a near infra-red light-emitting diode. Chem Sci 11:1026510278.
In a study of pregnant women in Bangladesh, taking vitamin D supplements was associated with nonsignificant increases in lead levels, but significant increases in cord blood levels of lead and cadmium, according to NIEHS researchers and their collaborators. Vitamin D is important for building healthy bones, but animal studies indicate it increases the absorption of toxic metals a body is exposed to, such as lead, cadmium, manganese, and mercury. The study was the first to examine the effect of prenatal vitamin D supplementation and blood metal levels in a randomized clinical trial.
In the study, 1,300 pregnant women were randomized into groups that received a placebo or weekly doses of either 4,200, 16,800, or 28,000 international units (IU) of vitamin D3.
Randomization occurred in the second trimester and supplementation or placebo were continued throughout pregnancy. At delivery, maternal blood and umbilical cord blood samples were collected, and researchers measured their cadmium, lead, mercury, and manganese levels using a technique called inductively coupled plasma mass spectrometry. The pregnant women who received vitamin D supplementation showed no significant increase in blood metal concentrations compared to the placebo group. However, they were more likely to have infants with higher cord blood lead levels and with detectable cadmium. The authors say further investigation is needed since there is no safe level of toxic metals for infants. (VP)
Citation:Jukic AMZ, Zuchniak A, Qamar H, Ahmed T, Mahmud AA, Roth DE. 2020. Vitamin D treatment during pregnancy and maternal and neonatal cord blood metal concentrations at delivery: Results of a randomized controlled trial in Bangladesh. Environ Health Perspect 128(11):117007.
NIEHS researchers and their collaborators have revealed that genetic factors contribute to development of hypothalamic amenorrhea (HA), a condition in which menstruation stops in women of reproductive age. The finding provides new insight into the development of HA and womens reproductive health.
Studies have shown that HA is more prevalent in women with excessive exercise, food restriction, or psychological stress. Both physical and emotional stressors could cause altered secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus in the brain. GnRH deficiency, in turn, impairs the synthesis of gonadotropins that are essential for reproduction and fertility and leads to hypogonadotropic hypogonadism (HH). Several rare, pathogenic sequence variants in genes that control the development or function of GnRH have been identified in individuals with a rare syndrome called isolated hypogonadotropic hypogonadism (IHH), an inherited form of HH. Due to the varied menstrual and hormonal response to similar stressors, this study investigated whether genetic variation influenced individual susceptibility to known risk factors for HA.
The researchers sequenced all the protein-coding regions of genes in women with HA and women in the control group. After comparing the frequency of rare variants in more than 50 IHH-associated genes, they found HA patients had a greater burden of variants than the control heathy women, confirming the genetic impact on the development of HA. (QX)
Citation:Delaney A, Burkholder AB, Lavender CA, Plummer L, Mericq V, Merino PM, Quinton R, Lewis KL, Meader BN, Albano A, Shaw ND, Welt CK, Martin KA, Seminara SB, Biesecker LG, Bailey-Wilson JE, Hall JE. 2020. Increased burden of rare sequence variants in GnRH-associated genes in women with hypothalamic amenorrhea. J Clin Endocrinol Metab; doi: 10.1210/clinem/dgaa609 [Online 1 September 2020].
(Sanya Mehta is an Intramural Research Training Award [IRTA] postbaccalaureate fellow in the NIEHS Matrix Biology Group. Victoria Placentra is an IRTA postbaccalaureate fellow in the NIEHS Mutagenesis and DNA Repair Regulation Group. Saniya Rattan, Ph.D., is an IRTA fellow in the NIEHS Reproductive Developmental Biology Group. Nancy Urbano is an IRTA postbaccalaureate fellow in the DNTP Predictive Toxicology and Screening Group. Qing Xu is a biologist in the NIEHS Metabolism, Genes, and Environment Group.)
See the original post here:
Environmental Factor - January 2021: Intramural Papers of the Month - Environmental Factor Newsletter
- NIH awards nearly $2M to Huebsch for study | The Source - Washington University in St. Louis Newsroom - August 31st, 2021
- Shoreline Launches with $4 Billion in Partnerships PharmaLive - PharmaLive - August 31st, 2021
- Bone Therapeutics announces topline results from Phase III knee osteoarthritis study with its enhanced viscosupplement JTA-004 - GlobeNewswire - August 31st, 2021
- Roslin Tech in multi-million bid to fund sustainable food - HeraldScotland - August 31st, 2021
- Global Induced Pluripotent Stem Cells Market Industry Analysis, Post COVID-19 Impact, Emerging Trends, Business Growth by 2027||Fate Therapeutics,... - July 22nd, 2021
- Bayer's BlueRock Therapeutics gains FDA fast track for Parkinson's disease cell therapy - PMLiVE - July 22nd, 2021
- Global Induced Pluripotent Stem Cell (iPSC) Market to Reach $2.3 Billion by 2026 - PRNewswire - July 7th, 2021
- Impact of NK cell-based therapeutics for Lung Cancer Therapy | BTT - Dove Medical Press - July 7th, 2021
- Caribou eyes $100M IPO as it aims off-the-shelf CAR-Ts at the clinic - FierceBiotech - July 7th, 2021
- Genexine, Toolgen to co-develop CAR-NK cell gene therapy - Korea Biomedical Review - July 7th, 2021
- Reversal of biological age detected in mouse and human embryos - BioNews - July 7th, 2021
- Century Therapeutics Announces Closing of Initial Public Offering and Full Exercise of Underwriters' Option to Purchase - GlobeNewswire - June 25th, 2021
- Univ. of Washington and Sana researchers use gene editing to prep stem cells for heart repair - GeekWire - June 25th, 2021
- Ubiquitination is essential for recovery of cellular activities after heat shock - Science Magazine - June 25th, 2021
- The CCL2-CCR2 astrocyte-cancer cell axis in tumor extravasation at the brain - Science Advances - June 25th, 2021
- Pharmacogenomic approach to cure the pain of the 'burning man' - Lab + Life Scientist - June 25th, 2021
- The Stem Cell Assay Market To Grow Through Mergers Amongst Market Participants The Courier - The Courier - June 25th, 2021
- Accelerated Biosciences' Immune-Privileged Human Trophoblast Stem Cells (hTSCs) Offer Breakthrough Opportunities in Cancer-Targeting Therapeutics and... - May 15th, 2021
- Study Models the Effect of Herpes Infection on Fetal Brain Development - Pharmacy Times - May 15th, 2021
- Induced Pluripotent Stem Cells Market is set for Lucrative Growth | Top Companies Thermo Fisher Scientific Inc., FUJIFILM Corporation, KSU | The... - May 15th, 2021
- Stem Cell Therapy Market by Type, Therapeutic Application and Cell Source - Global Forecasts to 2026 - ResearchAndMarkets.com - Business Wire - May 15th, 2021
- Global Induced Pluripotent Market Showing Impressive Growth by 2027||Thermo Fisher Scientific; Cell Applications, Inc.; Axol Bioscience Ltd.;... - May 15th, 2021
- Global Induced Pluripotent Stem Cells Market 2020 Top Manufactures, Growth Opportunities and Investment Feasibility 2025 The Courier - The Courier - May 3rd, 2021
- Stem Cell Therapy Market worth $401 million by 2026 - Exclusive Report by MarketsandMarkets - PRNewswire - May 3rd, 2021
- Fate Therapeutics Announces Four Presentations at the 2021 ASGCT Annual Meeting - GlobeNewswire - May 3rd, 2021
- Induced Pluripotent Stem Cells (iPSCs) Market 2021 Is Booming Across the Globe by Share, Size, Growth, Segments and Forecast to 2027 | Top Players... - May 3rd, 2021
- Induced Pluripotent Stem Cells (iPSCs) Market 2021 Industry Size, Share, Growth and Top Companies Analysis- Fujifilm Holding Corporation (CDI),... - May 3rd, 2021
- A New CRISPR Tool Flips Genes On and Off Like a Light Switch - Singularity Hub - May 3rd, 2021
- Stem Cell Characterization Kits Market Report 2021 by Global Key Players, Types, Applications, Countries, Size, Forecast to 2027 Good News Gum - Good... - May 3rd, 2021
- Induced Pluripotent Stem Cells Market Growth Opportunities, Analysis and Forecasts Report 2020-2026 with key players position (Fujifilm Holding... - February 17th, 2021
- Cytovia Therapeutics and Cellectis Partner to Develop TALEN Gene-Edited iPSC-Derived Natural Killer Cells - BioSpace - February 17th, 2021
- Can we freeze them? Yes we can, says Nkarta - Vantage - February 17th, 2021
- Global Induced Pluripotent Market Positive Outlook, Revenue Generation & Leading Manufacturers, Forecast 2026||CELGENE CORPORATION; Astellas... - February 17th, 2021
- Induced Pluripotent Stem Cells Market Growth, Competitive Landscape, Research Methodology, Business Opportunities, Statistics and Industry Analysis... - February 17th, 2021
- Evotec and Medical Center Hamburg-Eppendorf Enter Partnership to Develop iPSC-Based Tissue Therapy f - PharmiWeb.com - February 4th, 2021
- Breakthrough stem cell therapy may reverse life-threatening conditions in dogs - Study Finds - February 4th, 2021
- SLAS Technology Special Collection on Artificial Intelligence in Process Automation Available Now - Newswise - February 4th, 2021
- Exacis Biotherapeutics Announces Key Addition To Its Executive Leadership Team With Dirk Huebner MD Joining As Chief Medical Officer - PRNewswire - February 4th, 2021
- Induced Pluripotent Stem Cells Market 2020 Global Share, Growth, Size, Opportunities, Trends, Regional Overview, Leading Company Analysis And Forecast... - February 4th, 2021
- Money on the Move: January 27 February 2 - BioSpace - February 4th, 2021
- Poultry Healthcare Products Market Share, Growth, Statistics, by Application, Production, Revenue & Forecast to 2025 - AlgosOnline - January 27th, 2021
- Impact Of Covid 19 On Stem Cells Industry 2020 Market Challenges, Business Overview And Forecast Research Study 2026 Murphy's Hockey Law - Murphy's... - January 27th, 2021
- SREBP1 suppresses the differentiation and epithelial function of hiPSC-derived endothelial cells by inhibiting the microRNA199b-5p pathway - DocWire... - January 25th, 2021
- Induced Pluripotent Stem Cells Market Segmentation and Analysis by Latest Trends, Development and Growth by Trending Regions 2020 with key players... - January 25th, 2021
- Induced Pluripotent Stem Cells (iPSCs) Market to Witness Massive Growth During 2021-2027 | Fujifilm Holding Corporation (CDI), Ncardia, Sumitomo... - January 25th, 2021
- Hands across the water as bio bonds stand test of time | Business Weekly - Business Weekly - January 25th, 2021
- Exercise mimetics and JAK inhibition attenuate IFN-induced wasting in engineered human skeletal muscle - Science Advances - January 25th, 2021
- Can Science Save the Northern White Rhino? - Freethink - January 25th, 2021
- Induced Pluripotent Stem Cells Market to Grow with an Impressive CAGR - Farming Sector - January 9th, 2021
- Accelerating cell-based therapies by providing safe therapeutic MSC products - BioSpace - January 9th, 2021
- Exacis Biotherapeutics Announces Its Launch and mRNA Technology In-Licensing For Targeted CAR-NK And CAR-T Cell Cancer Therapies | DNA RNA and Cells |... - January 9th, 2021
- Global Induced Pluripotent Stem Cells Market To Witness Huge Gains Over 2020-2026 - Factory Gate - December 28th, 2020
- Exosomes act as messengers and decoys to save healthy cells from viral infection - Massive Science - December 28th, 2020
- Scientists have restored youth to aging eyes in mice - Massive Science - December 21st, 2020
- Top Technical Advances of 2020 - The Scientist - December 21st, 2020
- A new psychedelic drug gives psychiatric benefits without causing hallucinations - Massive Science - December 21st, 2020
- I Peace, Inc. and Avery Therapeutics announce collaboration to bring iPSC derived cell therapy for heart failure to the clinic - PRNewswire - December 17th, 2020
- Network of Genes Involved in Congenital Heart Disease Identified - Technology Networks - December 17th, 2020
- Global Induced Pluripotent Market 2020-26 Steering Forces Heading Towards Impressive CAGR With CELGENE CORPORATION; Astellas Pharma Inc.; Thermo... - December 17th, 2020
- Global Induced Pluripotent Stem Cells (iPSCs) Market Expectable to Exceed Global Market Revenue, Size, Segments and Market Competition Trend to... - December 14th, 2020
- Evotec and Sartorius Partner with Start-Up Curexsys on IPSC-Based Therapeutic Exosome Approach - BioSpace - December 9th, 2020
- Multiple gene edits and computer simulations could help treat rare genetic diseases - University of Wisconsin-Madison - December 9th, 2020
- Cytovia Therapeutics announces plans to initiate in 2021 Clinical Development of Universal iPSC NK Cell Therapy for Hematological and Solid Tumors -... - December 9th, 2020
- Fate Therapeutics Reports Positive Interim Data from its Phase 1 Study of FT516 in Combination with Rituximab for B-cell Lymphoma - GlobeNewswire - December 9th, 2020
- Constantly Growing Applications and Innovations to Push Sales of Amniotic Membrane Market Up To ~US$2.4 Bn by 2027, Observes TMR - PRNewswire - December 9th, 2020
- Tulane researcher shows enhanced therapeutic stem cell migration improves neurodegenerative disease - News from Tulane - December 8th, 2020
- Researchers restore lost sight in mice, offering clues to reversing aging - Science Magazine - December 8th, 2020
- Fate Therapeutics Reports Positive Interim Data from its Phase 1 Study of FT516 in Combination with Rituximab for B-cell Lymphoma | DNA RNA and Cells... - December 8th, 2020
- Bayer and Atara Biotherapeutics in CAR T-cell therapy deal - BioPharma-Reporter.com - December 8th, 2020
- Repairing the Brain With Stem Cells? A Conversation With Prof. Jack Price - Being Patient - December 3rd, 2020
- Global Induced Pluripotent Stem Cells Market Size, Comprehensive Analysis, Development Strategy, Future Plans and Industry Growth with High CAGR by... - December 3rd, 2020
- Industry Verticals: Induced Pluripotent Stem Cells (iPSC) Market Latest and updated Scope and Application 2020-2027 - The Blend - December 3rd, 2020
- Bayer Launches Cell and Gene Therapy Platform to Maximize Recent Acquisitions - PharmaLive - December 3rd, 2020
- Stem Cells Market Size on Target to Reach US$ 17.79 Billion 2027 - Cheshire Media - December 3rd, 2020
- Bayer establishes Cell and Gene Therapy Platform to accelerate pharmaceutical innovation | More News | News Channels - PipelineReview.com - December 3rd, 2020
- Growing Value of Stem Cells in Medicine to Create a US$2,4 Billion Opportunity for Induced Pluripotent Stem Cell ((iPSC) - GlobeNewswire - November 27th, 2020
- Induced Pluripotent Stem Cells Market New Research Study Report with Size, Share, Trends, Emerging Applications, Opportunities and Worldwide Analysis... - November 27th, 2020
- Induced Pluripotent Stem Cells (iPSCs) Market Applications, Types and Future Ou - News by aeresearch - November 27th, 2020
- Research Paper Showing ProtoKinetix AAGP Enhanced Stem Cell Derived Retina Precursor Cells Restoration of Vision - Business Wire - November 27th, 2020
- Induced Pluripotent Stem Cells Market 2020: Enhanced Growth, Recent Trends and Major Companies are Fujifilm Holding Corporation, Astellas Pharma, Fate... - November 27th, 2020