scholarly journals Time-dependent effect of 1,6-hexanediol on biomolecular condensates and 3D chromatin organization

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xinyi Liu ◽  
Shaoshuai Jiang ◽  
Lin Ma ◽  
Jiale Qu ◽  
Longying Zhao ◽  
...  
Keyword(s):  
Long Range ◽  
Term Treatment ◽  
Chromatin Organization ◽  
Short Term ◽  
Short Term Treatment ◽  
Time Resolved ◽  
Cellular Processes ◽  
Short Term Exposure ◽  
Long Range Interactions ◽  
Time Dependent Effect

Abstract Background Biomolecular condensates have been implicated in multiple cellular processes. However, the global role played by condensates in 3D chromatin organization remains unclear. At present, 1,6-hexanediol (1,6-HD) is the only available tool to globally disrupt condensates, yet the conditions of 1,6-HD vary considerably between studies and may even trigger apoptosis. Results In this study, we first analyzed the effects of different concentrations and treatment durations of 1,6-HD and found that short-term exposure to 1.5% 1,6-HD dissolved biomolecular condensates whereas long-term exposure caused aberrant aggregation without affecting cell viability. Based on this condition, we drew a time-resolved map of 3D chromatin organization and found that short-term treatment with 1.5% 1,6-HD resulted in reduced long-range interactions, strengthened compartmentalization, homogenized A-A interactions, B-to-A compartment switch and TAD reorganization, whereas longer exposure had the opposite effects. Furthermore, the long-range interactions between condensate-component-enriched regions were markedly weakened following 1,6-HD treatment. Conclusions In conclusion, our study finds a proper 1,6-HD condition and provides a resource for exploring the role of biomolecular condensates in 3D chromatin organization.

Ethanol stimulates glucose uptake and translocation of GLUT-4 in H9c2 myotubes via a Ca2+-dependent mechanism

2000 ◽  
Vol 279 (6) ◽  
pp. E1358-E1365 ◽  
Author(s):  
Bo Yu ◽  
Adrienne Schroeder ◽  
Laura E. Nagy
Keyword(s):  
Plasma Membrane ◽  
Glucose Uptake ◽  
Glucose Homeostasis ◽  
Term Treatment ◽  
Glucose Disposal ◽  
Phosphatidylinositol 3 Kinase ◽  
Short Term ◽  
Short Term Treatment ◽  
Glut 4 ◽  
Short Term Exposure

Short-term exposure to ethanol impairs glucose homeostasis, but the effects of ethanol on individual components of the glucose disposal pathway are not known. To understand the mechanisms by which ethanol disrupts glucose homeostasis, we have investigated the direct effects of ethanol on glucose uptake and translocation of GLUT-4 in H9c2 myotubes. Short-term treatment with 12.5–50 mM ethanol increased uptake of 2-deoxyglucose by 1.8-fold in differentiated myotubes. Pretreatment of H9c2 myotubes with 100 nM wortmannin, an inhibitor of phosphatidylinositol 3-kinase, had no effect on ethanol-induced increases in 2-deoxyglucose uptake. In contrast, preincubation with 25 μM dantrolene, an inhibitor of Ca2+release from the sarcoplasmic reticulum, blocked the stimulation of 2-deoxyglucose uptake by ethanol. Increased 2-deoxyglucose uptake after ethanol treatment was associated with a decrease in small intracellular GLUT-4 vesicles and an increase in GLUT-4 localized at the cell surface. In contrast, ethanol had no effect on the quantity of GLUT-1 and GLUT-3 at the plasma membrane. These data demonstrate that physiologically relevant concentrations of ethanol disrupt the trafficking of GLUT-4 in H9c2 myotubes resulting in translocation of GLUT-4 to the plasma membrane and increased glucose uptake.

scholarly journals Effect of short-term exposure of rats to dehydroepiandrosterone on the hepatic metabolism of dimethylnitrosamine

1989 ◽  
Vol 262 (3) ◽  
pp. 985-988 ◽  
Author(s):  
H R Prasanna ◽  
R W Hart ◽  
P N Magee
Keyword(s):  
Hepatic Metabolism ◽  
Liver Weight ◽  
Term Treatment ◽  
Sprague Dawley ◽  
Short Term ◽  
Short Term Treatment ◽  
Adrenal Steroid ◽  
Methylation Of Dna ◽  
Short Term Exposure ◽  
Hepatic Proteins

The influence of short-term treatment with dehydroepiandrosterone (DHEA), a naturally occurring adrenal steroid, on hepatic metabolism and macromolecular interactions of the hepatocarcinogen dimethylnitrosamine (NDMA) was investigated in male Sprague-Dawley rats. Liver weight, total tissue protein (P less than 0.05), microsomal and cytosolic proteins and cytochrome P-450 (P less than 0.001) were all significantly increased in rats treated orally with DHEA (300 mg/kg body wt., suspended in 1.0 ml of sesame oil). The hepatic DNA content was not altered, however. Methylation of DNA by NDMA was reduced significantly in DHEA-treated rats (P less than 0.05). The binding of [14C]NDMA to hepatic proteins was greater in DHEA-treated rats. The results suggest that short-term treatment of rats with DHEA enhances the binding of NDMA-derived metabolites to hepatic proteins, resulting in the protection of DNA from the damaging effects of NDMA.

Ganciclovir induces reproductive hazards in male rats after short-term exposure

1997 ◽  
Vol 16 (9) ◽  
pp. 505-511 ◽  
Author(s):  
AS Faqi ◽  
A. Klug ◽  
H-J. Merker ◽  
I. Chahoud
Keyword(s):  
Term Treatment ◽  
Male Reproduction ◽  
Male Rats ◽  
Short Term ◽  
Short Term Treatment ◽  
Adult Rats ◽  
Clear Cut ◽  
Treat Ment ◽  
Short Term Exposure ◽  
Cut Time

1 The effect of short-term treatment of ganciclovir on male reproduction in adult rats was studied. The animals were treated subcutaneously with either a single dose of 60 mg/kg daily for 5 days (Gan5day) or with 100 mg/kg administered three times at 4 h- intervals (Gan1day). The effects were investigated every 2 weeks up to 8 weeks, followed by investigations 16 and 24 weeks after treatment to detect the potential of recovery. 2 Time to mating was significantly increased in Gan1day group. The pregnancy index and outcome were only decreased 8 weeks (Gan5day and Gan1day) or 16 weeks (Gan1day) after treatment. 3 The lowest values of sperm variables studied were registered 8 weeks after treatment: The number of spermatid was reduced up to 4% (Gan5day) or 2% (Gan1day) of control; the sperm number was 5% and 8% of control in Gan5day and Gan1day, respectively. Over 80% of sperm were abnormal in Gan5day group, and only few normal sperm was detected in Gan1day group. 4 Morphological investigation of testes revealed a clear- cut time-dependency effect. Four weeks after treat ment distinct alterations were located exclusively in the peripheral part of the tubuli which included fat inclusions, cell and pyknotic nuclear debris and swellings of Sertoli cells. The effect was reversible 24 weeks after treatment. 5 Ganciclovir induces testicular damage and affects sperm variables after short-term exposure. The in tensity and degree of the hazards varied in between the time of investigation after treatment.

Amorphous silica nanoparticles induced spleen and liver toxicity after acute intravenous exposure in male and female rats

2021 ◽  
pp. 074823372110105
Author(s):  
Roberta Tassinari ◽  
Andrea Martinelli ◽  
Mauro Valeri ◽  
Francesca Maranghi
Keyword(s):  
Amorphous Silica ◽  
Liver Toxicity ◽  
Female Rats ◽  
Histopathological Analysis ◽  
Short Term ◽  
Short Term Treatment ◽  
Male And Female ◽  
Male And Female Rats ◽  
Target Organs ◽  
Short Term Exposure

Synthetic amorphous silica (SAS) nanomaterial – consisting of aggregates and agglomerates of primary silicon dioxide (SiO2) particles in the nanorange (<100 nm) – is commonly used as excipient in pharmaceuticals, in cosmetics and as food additive (E551). The available data suggest that SAS nanoparticles (NP) after intravenous (IV) exposure persist in liver and spleen; however, insufficient data exist to verify whether SAS may also induce adverse effects. The aim of the present study was to verify the potential long-term effects of SAS NP (NM-203) on spleen and liver as target organs following short-term exposure. Adult male and female Sprague-Dawley rats were treated by IV injection in the tail vein with a single (1-day) dose (SD) and repeated (5-day) doses (RD) of 20 mg/kg bw per day of SAS dispersed in sterile saline solution as vehicle. Histopathological examinations of target organs were performed after 90 days. Tissue biodistribution and full characterization of NM-203, primary particle size 13–45 nm, was performed within the framework of the Nanogenotox project. No mortality or general toxicity occurred; histopathological analysis showed splenomegaly in the RD group accompanied by inflammatory granulomas in both sexes. Granulomas were also present in liver parenchyma in the RD (both sexes) and SD groups (male only). The histopathological results indicated that SAS NP have the potential to persist and induce sex-specific chronic inflammatory lesions in spleen and liver upon short-term treatment. Overall, the data showed that the widespread use of silica in drugs might elicit chronic reactions in spleen and liver prompting to the need of further investigations on the safety of SAS NP.

scholarly journals KIDNEY INJURY MOLECULE-1 AS AN EARLY AMIKACIN-INDUCED NEPHROTOXICITY MARKER IN PATIENTS WITH SEPSIS HOSPITALIZED IN THE INTENSIVE CARE UNIT

2019 ◽  
pp. 277-279
Author(s):  
TRISNI UNTARI DEWI ◽  
INSTIATY . ◽  
RUDIANTO SEDONO ◽  
GESTINA ALISKA ◽  
MUHAMMAD KHIFZHON AZWAR ◽  
...  
Keyword(s):  
Intensive Care ◽  
Kidney Injury ◽  
Term Treatment ◽  
Short Term ◽  
Short Term Treatment ◽  
Safe Level ◽  
Study Results ◽  
Early Biomarker ◽  
Kidney Injury Molecule 1 ◽  
Trough Plasma

Objective: This study sought to determine the correlation between trough plasma amikacin concentrations and urinary normalized kidney injurymolecule-1 (KIM-1) concentrations as an early biomarker of nephrotoxicity in patients with sepsis who are hospitalized in an intensive care unit.Methods: In this pilot study, 12 patients with sepsis were treated with amikacin 1000 mg/day between May 2015 and September 2015. The correlationbetween trough plasma amikacin concentrations measured after the third dose and the elevation of urinary normalized KIM-1 concentrations afterthe third amikacin dose relative to the first/second dose was evaluated.Results: In total, three patients had trough plasma amikacin concentrations exceeding the safe level (>10 μg/ml). Furthermore, eight patientsdisplayed higher normalized KIM-1 concentrations after third dose than after the first/second dose; however, there was no correlation betweentrough amikacin concentrations and the elevation of urinary normalized KIM-1 concentrations (r=0.3, p=0.3).Conclusion: The study results illustrated that short-term treatment with an amikacin dose of 1000 mg/day was generally safe in patients with sepsis.

Instrumentation in Voice Assessment and Treatment

1997 ◽  
Vol 6 (4) ◽  
pp. 9-16 ◽  
Author(s):  
Alison Behrman ◽  
Robert F. Orlikoff
Keyword(s):  
Clinical Practice ◽  
Scientific Method ◽  
Term Treatment ◽  
Treatment Goals ◽  
Short Term ◽  
Short Term Treatment ◽  
Voice Assessment ◽  
Assessment And Treatment ◽  
Computer Based ◽  
The Voice

Sophisticated, computer-based instrumentation has become increasingly available to the voice clinician. Yet substantial questions remain regarding its clinical necessity and usefulness. A theoretical model based on the scientific method is developed as a framework that can be used to guide the clinician in the selection and application of instrumental measures. Using the process of hypothesis testing, instrumentation is presented as an integral component of clinical practice. The uses of instrumental measures, and their relevance to long- and short-term treatment goals, are addressed. Clinical examples are presented to illustrate the incorporation of instrumentation and the scientific method into assessment and treatment.

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