Prenatal low-dose DEHP exposure induces metabolic adaptation and obesity: Role of hepatic thiamine metabolism

Hepatocellular carcinoma (HCC) remains one of the most lethal human cancer globally. For advanced HCC, curable plan for advanced HCC is yet to be established, and the prognosis remains poor. The detail mechanisms underlying the progression of HCC tumorigenicity and the corruption of tumor microenvironment (TME) is complex and inconclusive. A growing body of studies demonstrate microRNAs (miRs) are important regulators in the tumorigenicity and TME development. Notably, mounting evidences indicate miR-29a play a crucial role in exerting hepatoprotective effect on various types of stress and involved in the progression of HCC, which elucidates their potential theragnostic implications. In this review, we reviewed the advanced insights into the detail mechanisms by which miR-29a dictates carcinogenesis, epigenetic program, and metabolic adaptation, and implicated in the sponging activity of competitive endogenous RNAs (ceRNA) and the TME components in the scenario of HCC. Furthermore, we highlighted its clinical significance in diagnosis and prognosis, as well as the emerging therapeutics centered on the activation of miR-29a.

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The Role of the Pathogen Dose and PI3Kγ in Immunometabolic Reprogramming of Microglia for Innate Immune Memory

International Journal of Molecular Sciences ◽

10.3390/ijms22052578 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2578

Author(s):

Trim Lajqi ◽

Christian Marx ◽

Hannes Hudalla ◽

Fabienne Haas ◽

Silke Große ◽

...

Keyword(s):

Oxygen Consumption ◽

Immune Tolerance ◽

Immune Cells ◽

Low Dose ◽

Innate Immune ◽

Immune Memory ◽

Innate Immune Cells ◽

Atp Production ◽

Dose Dependent

Microglia, the innate immune cells of the CNS, exhibit long-term response changes indicative of innate immune memory (IIM). Our previous studies revealed IIM patterns of microglia with opposing immune phenotypes: trained immunity after a low dose and immune tolerance after a high dose challenge with pathogen-associated molecular patterns (PAMP). Compelling evidence shows that innate immune cells adopt features of IIM via immunometabolic control. However, immunometabolic reprogramming involved in the regulation of IIM in microglia has not been fully addressed. Here, we evaluated the impact of dose-dependent microglial priming with ultra-low (ULP, 1 fg/mL) and high (HP, 100 ng/mL) lipopolysaccharide (LPS) doses on immunometabolic rewiring. Furthermore, we addressed the role of PI3Kγ on immunometabolic control using naïve primary microglia derived from newborn wild-type mice, PI3Kγ-deficient mice and mice carrying a targeted mutation causing loss of lipid kinase activity. We found that ULP-induced IIM triggered an enhancement of oxygen consumption and ATP production. In contrast, HP was followed by suppressed oxygen consumption and glycolytic activity indicative of immune tolerance. PI3Kγ inhibited glycolysis due to modulation of cAMP-dependent pathways. However, no impact of specific PI3Kγ signaling on immunometabolic rewiring due to dose-dependent LPS priming was detected. In conclusion, immunometabolic reprogramming of microglia is involved in IIM in a dose-dependent manner via the glycolytic pathway, oxygen consumption and ATP production: ULP (ultra-low-dose priming) increases it, while HP reduces it.

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Krill oil and low-dose aspirin combination mitigates experimentally induced silicosis in rats: role of NF-κB/TGF-β1/MMP-9 pathway

Environmental Science and Pollution Research ◽

10.1007/s11356-020-11921-7 ◽

2021 ◽

Author(s):

Ahmed G. Abd Elhameed

Keyword(s):

Low Dose ◽

Krill Oil ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Tgf Β1 ◽

Experimentally Induced

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Possible role of low-dose etoposide therapy for hemophagocytic lymphohistiocytosis by COVID-19

International Journal of Hematology ◽

10.1007/s12185-020-02888-9 ◽

2020 ◽

Vol 112 (1) ◽

pp. 122-124 ◽

Cited By ~ 5

Author(s):

Akiyoshi Takami

Keyword(s):

Hemophagocytic Lymphohistiocytosis ◽

Low Dose

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Protective role of Convolvulus pluricaulis on lipid abnormalities in high-fat diet with low dose streptozotocin-induced experimental rat model

Journal of Ayurveda and Integrative Medicine ◽

10.1016/j.jaim.2020.06.011 ◽

2020 ◽

Vol 11 (4) ◽

pp. 426-431

Author(s):

Gaurav Garg ◽

Amol N. Patil ◽

Rohit Kumar ◽

Alka Bhatia ◽

Kripa Shanker Kasudhan ◽

...

Keyword(s):

Rat Model ◽

High Fat Diet ◽

Low Dose ◽

Protective Role ◽

High Fat ◽

Experimental Rat Model ◽

Convolvulus Pluricaulis ◽

Lipid Abnormalities

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Reactive oxygen species in cell responses to toxic agents

Human & Experimental Toxicology ◽

10.1191/0960327102ht216oa ◽

2002 ◽

Vol 21 (2) ◽

pp. 85-90 ◽

Cited By ~ 87

Author(s):

L E Feinendegen

Keyword(s):

Radiation Exposure ◽

Mammalian Cells ◽

Low Dose ◽

X Rays ◽

Low Dose Radiation ◽

Cell Responses ◽

Toxic Agents ◽

Particle Tracks ◽

Dose Radiation

This review first summarizes experimental data on biological effects of different concentrations of ROS in mammalian cells and on their potential role in modifying cell responses to toxic agents. It then attempts to link the role of steadily produced metabolic ROS at various concentrations in mammalian cells to that of environmentally derived ROS bursts from exposure to ionizing radiation. The ROS from both sources are known to both cause biological damage and change cellular signaling, depending on their concentration at a given time. At low concentrations signaling effects of ROS appear to protect cellular survival and dominate over damage, and the reverse occurs at high ROS concentrations. Background radiation generates suprabasal ROS bursts along charged particle tracks several times a year in each nanogram of tissue, i.e., average mass of a mammalian cell. For instance, a burst of about 200 ROS occurs within less than a microsecond from low-LET irradiation such as X-rays along the track of a Compton electron (about 6 keV, ranging about 1 μm). One such track per nanogram tissue gives about 1 mGy to this mass. The number of instantaneous ROS per burst along the track of a 4-meV ¬-particle in 1 ng tissue reaches some 70000. The sizes, types and sites of these bursts, and the time intervals between them directly in and around cells appear essential for understanding low-dose and low dose-rate effects on top of effects from endogenous ROS. At background and low-dose radiation exposure, a major role of ROS bursts along particle tracks focuses on ROS-induced apoptosis of damage-carrying cells, and also on prevention and removal of DNA damage from endogenous sources by way of temporarily protective, i.e., adaptive, cellular responses. A conclusion is to consider low-dose radiation exposure as a provider of physiological mechanisms for tissue homoeostasis.

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