Aloe vera gel extract: Safety evaluation for acute and chronic oral administration in Sprague-Dawley rats and anticancer activity in breast and lung cancer cells.

Ethnopharmacological Relevance: Aloe vera (L.) Burm. f.

Acquisition of temozolomide resistance by the rat C6 glioma cell line increases cell migration and side population phenotype.

Cancer stem cells are reportedly associated with drug resistance in glioma, but there are conflicting findings on the effects of cancer stem cells on drug resistance. The aim of the present study was to identify the underlying mechanisms of drug resistance in rat C6 glioma cells, through the use of Transwell invasion assays, flow cytometric and western blot analyses as well as immunohistochemical staining. The results revealed that acquisition of drug resistance by C6 cells enhanced migration ability in vivo and in vitro.

ZC4H2 stabilizes RNF220 to pattern ventral spinal cord through modulating Shh/Gli signaling.

ZC4H2 encodes a C4H2 type zinc-finger nuclear factor, the mutation of which has been associated with disorders with various clinical phenotypes in human, including developmental delay, intellectual disability and dystonia. ZC4H2 has been suggested to regulate spinal cord patterning in zebrafish as a co-factor for RNF220, an ubiquitin E3 ligase involved in Gli signaling. Here we showed that ZC4H2 and RNF220 knockout animals phenocopy each other in spinal patterning in both mouse and zebrafish, with mispatterned progenitor and neuronal domains in the ventral spinal cord.

Fine-Tuning of Shh/Gli Signaling Gradient by Non-proteolytic Ubiquitination during Neural Patterning.

Sonic Hedgehog (Shh) signaling plays crucial roles in patterning the ventral neural tube, which is transformed into opposing gradients of repressor and activator forms of Glis. Here, we show that the fine-tuning of the shape of the Gli gradients through non-proteolytic ubiquitination-mediated nuclear exportation plays an important role in the control of local neural cell fate. Loss of RNF220, a ventral neural-specific ubiquitin E3 ligase, leads to ventral expansion of the intermediate V0 and dorsal expansion of the ventral V3 neurons, while reducing the V1, V2, and motor neurons between them.

The Alternative 2/1 Schedule of Sunitinib is Superior to the Traditional 4/2 Schedule in Patients With Metastatic Renal Cell Carcinoma: A Meta-analysis.

Alternate sunitinib schedules attracted the interest of oncologists recently owing to their superior safety profile. This meta-analysis compared the tolerability and efficacy of a new alternative dosing schedule (2 weeks on/1 week off) of sunitinib with the traditional 4/2 schedule in patients with metastatic renal cell carcinoma (mRCC). Studies were retrieved from Medline, Cochrane Central, Scopus, Embase, and Web of Science databases.

ZC4H2 stabilizes Smads to enhance BMP signalling, which is involved in neural development in .

Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance, differentiation and embryonic development. Intracellularly, BMP signalling is mediated by Smad proteins, which are regulated post-transcriptionally through reversible phosphorylation and ubiquitination. ZC4H2 is a small nuclear protein associated with intellectual disability and neural development in humans.

Nicotinic acid impairs assembly of leading edge in glioma cells.

Malignant glioma is a clinically formidable disease. It commonly leads to death within 5 years after diagnosis. Physicians are often baffled since the inevitable diffuse invasion deteriorates clinical outcomes rapidly.

Nicotinic acid inhibits glioma invasion by facilitating Snail1 degradation.

Malignant glioma is a formidable disease that commonly leads to death, mainly due to the invasion of tumor cells into neighboring tissues. Therefore, inhibition of tumor cell invasion may provide an effective therapy for malignant glioma. Here we report that nicotinic acid (NA), an essential vitamin, inhibits glioma cell invasion in vitro and in vivo.

Trip12 is an E3 ubiquitin ligase for USP7/HAUSP involved in the DNA damage response.

The deubiquitinating enzyme, USP7/HAUSP (herpesvirus-associated ubiquitin-specific protease), is a key regulator of the tumor suppressor p53 and plays a major role in regulating genome stability. Here, we report that the protein stability of USP7 is regulated by the ubiquitin-proteasome pathway. We identified the thyroid hormone receptor interactor 12 (Trip12) as a ubiquitin E3 ligase for USP7.

Elongator Protein 3 (Elp3) stabilizes Snail1 and regulates neural crest migration in Xenopus.

Elongator protein 3 (Elp3) is the enzymatic unit of the elongator protein complex, a histone acetyltransferase complex involved in transcriptional elongation. It has long been shown to play an important role in cell migration; however, the underlying mechanism is unknown. Here, we showed that Elp3 is expressed in pre-migratory and migrating neural crest cells in Xenopus embryos, and knockdown of Elp3 inhibited neural crest cell migration.

The ubiquitin ligase RNF220 enhances canonical Wnt signaling through USP7-mediated deubiquitination of β-catenin.

Wnt/β-catenin signaling plays critical roles in embryonic development and disease. Here, we identify RNF220, a RING domain E3 ubiquitin ligase, as a new regulator of β-catenin. RNF220 physically interacts with β-catenin, but instead of promoting its ubiquitination and proteasomal degradation, it stabilizes β-catenin and promotes canonical Wnt signaling.