RRM2 Regulates Hepatocellular Carcinoma Progression Through Activation of TGF-β/Smad Signaling and Hepatitis B Virus Transcription.

Background: Hepatocellular carcinoma (HCC) is a type of malignant tumor with high morbidity and mortality. Untimely treatment and high recurrence are currently the major challenges for HCC. The identification of potential targets of HCC progression is crucial for the development of new therapeutic strategies.

ACSL4 promotes malignant progression of Hepatocellular carcinoma by targeting PAK2 transcription.

Long-chain fatty acyl-Coa ligase 4 (ACSL4) is an important enzyme that converts fatty acids to fatty acyl-Coa esters, there is increasing evidence for its role in carcinogenesis. However, the precise role of ACLS4 in hepatocellular carcinoma (HCC) is not clearly understood. In the present study, we provide evidence that ACSL4 expression was specifically elevated in HCC and is associated with poor clinical outcomes.

Radioprotective effectiveness of a novel delta-tocotrienol prodrug on mouse hematopoietic system against Co gamma-ray irradiation through inducing granulocyte-colony stimulating factor production.

Considering the increasing risk of nuclear attacks worldwide, the development of develop potent and safe radioprotective agents for nuclear emergencies is urgently needed. γ-tocotrienol (GT3) and δ-tocotrienol (DT3) have demonstrated a potent radioprotective effect by inducing the production of granulocyte-colony stimulating factor (G-CSF) in vivo. However, their application is limited because of their low bioavailability.

Sequential administration of delta-tocotrienol ameliorates radiation-induced myelosuppression in mice and non-human primates through inducing G-CSF production.

To date only four recombinant growth factors, including Filgrastim (rhG-CSF), have been approved by FDA as radiomitigators to ameliorate hematopoietic acute radiation syndrome (H-ARS). These approved agents are not stable under room-temperature, needing to be stored at 2-8 °C, and would not be feasible in a mass casualty scenario where rapid and cost-effective intervention is crucial. Delta-tocotrienol (δ-T3H), the most potent G-CSF-inducing agent among vitamin E isoforms, exhibited efficiency and selectivity on G-CSF production in comparison with TLR and STING agonists in mice.

Dimethyl sulfoxide, a potent oral radioprotective agent, confers radioprotection of hematopoietic stem and progenitor cells independent of apoptosis.

In mass casualty events involving radiation exposure, there is a substantial unmet need for identifying and developing an orally bioavailable agent that can be used to protect the hematopoietic stem cell pool and regenerate hematopoiesis after radiation injury. Dimethyl sulfoxide (DMSO), a free-radical scavenger, has shown therapeutic benefits in many preclinical and clinical studies. This study investigates the radioprotective effects of DMSO on oral administration.

17α-Ethinyl-androst-5-ene-3β, 17β-diol, a Novel Potent Oral Radioprotective Agent, Confers Radioprotection of Hematopoietic Stem and Progenitor Cells in a Granulocyte Colony-Stimulating Factor-Independent Manner.

Purpose: The risk of radiation exposure is considered to have increased in recent years. For convenience and simple administration, development of an effective orally administered radioprotective agent is highly desirable. The steroid 5-androstene-3β, 17β-diol (5-AED) has been evaluated as both a radioprotector and a radiomitigator in mice and nonhuman primates; however, poor oral bioavailability has limited its development.