Cover: The cover image, by Anne E. Cress., is based on the Article Characterization of Laminin Binding Integrin Internalization in Prostate Cancer Cells, DOI: 10.1002/jcb.25673.

The intestinal mucosa is a rapidly turning-over tissue, completely renewing approximately every 5 days. Intestinal stem cells that maintain the mucosa and that can act as tumor initiating cells can be contributed by multiple compartments at or near the crypt base. Environmental factors—especially dietary factors—may play a major role in determining the complement of cell compartments that contribute functioning stem cells.

A novel role for phenotypic transcription factors in very early differentiation was recently observed and merits further study to elucidate what role this precocious expression may have in development. The RUNX1 transcription factor exhibits selective and transient upregulation during early mesenchymal differentiation.

The “mechanostat” principle may well characterize the oscillatory properties of the signal transduction mechanism that controls hard tissue metabolism and includes biochemical apart from mechanical stimuli.

We have previously shown in renal cells that expression of the water channel Aquaporin 2 (AQP2) increases the rate of cell proliferation. In this study, we investigated if the isoform 2 of the Na⁺/H⁺ exchanger (NHE2), the main ion transporter involved in RVI responses, contributed to the AQP2-increased renal cell proliferation. Our results showed that in AQP2-expressing cells NHE2 expression and activity are higher leading to an activation of a NHE2-mediated RVI response in the S phase of the cell cycle, which may be implicated in the increase the rate of cell proliferation.

Aqueous extracts (AE) of Australian cane toad skins induce upregulation of 5-HT_2A and D₂ receptos and enhance their interaction in a neuronal cell (CLU213) in vitro via G_q/11 G-protein PLCβ signaling pathway and c-FOS transcription factor activation. This could provide a molecular mechanism to develop AE of Australian cane toad skins as potential novel drug candidates to ameliorate OCD symptoms.

Hyperglycemic condition favors the establishment of a pro-inflammatory and pro-oxidant environment characterized by the induction of the COX-2/PGE2 axis. Stromal-derived PGE2, acting as a stimulator of IL-1 epithelial expression was one the factors that promotes the acquisition of motile properties by epithelial cells.

Diclofenac treatment causes stabilization of ubiquitylated misfolded proteins due to disturbed proteasomal function and elevates levels of pro-apoptotic proteasome target proteins. Induces mitochondrial dysfunction and cytochrome c release upon treatment of diclofenac into the cells.

We highlight the selenium compound as a possible alterative therapy under acyclovir treatment resistance.(PhSe)₂ treatment could overcome the majority of negative effects caused by infection.

We developed a rate kinetic model of internalization and determined the basal internalization rates of laminin binding integrins (α3 and α6) to be significantly different. Coordination existed between their internalization such that, the loss of α3 integrin expression increased the internalization of α6 integrin to early endosomes and cell–cell locations. The results are important in the context of collective migration during epithelial tumor dissemination and metastasis using α6 and α3 integrins.

Loss of the vitamin D receptor altered mineral homeostasis, enhanced the inflammatory state, and reduced hyperlipidemic profiles in Apoe^−/−;Vdr^−/− mice fed a high-fat diet. While these effects of VDR loss did not alter the rate of plaque progression in the double null mice, they fully prevented calcification as assessed by µCT and histological analyses. Thus, vitamin D and its receptor play an integral role in establishing conditions under which atherosclerotic plaques undergo the calcification process.

Treatment of the naturally derived flavonoid, 3,4′-dihydroxyflavone (3,4′-DHF) suppressed adipogenesis in murine 3T3-L1 pre-adipocytes and equine adipose-derived stromal cells (eADSCs) through differential modulation of ROS and kinase signaling pathways. These results suggest that the flavonoid can be used to regulate adipogenesis in ADSCs, which has potential therapeutic application in regenerative medicine or health care for humans and many sport or companion animals.

The mitochondrial antioxidant enzyme Mn-Superoxide Dismutase (Sod2) is essential for mammalian survival. Sod2 and the mutant Sod2 I91T, which corresponds to the human mutant Sod2 I82T, were cloned in sod2Δ strain. Although overexpression of Sod2 containing I91T mutation allows higher cell viability, longevity of cells is hampered, showing that in long-term this mutation is not neutral.

Biglycan intensifies TGF-β1–ALK5–Smad2/3 signaling pathway that mediates the suppression of syndecan-4 expression in vascular endothelial cells.

Method of adipose tissue collection affects some characteristics of stem cells isolated from this tissue type. At the current state of knowledge, the best method of ASCs collection for medical purposes is power-assisted liposuction.

Acidosis caused fast yet persistent mitochondrial hyperpolarization in cortical astrocytes. Such hyperpolarization could only be prevented by SC79, suggesting a role for Akt in maintaining resting mitochondrial potential.

Naringenin as a novel therapeutic drug has inhibitory effects on proliferation and migration of prostate cancer through depolarization of mitochondrial membranes as well as regulation of PI3K/AKT and MAPKs pathways.

Compounds substituted with electron-withdrawing groups at the selenium-bonded aromatic ring inhibited δ-ALA-D and Na⁺, K⁺-ATPase; Enzymatic activities were restored by a reducing agent, suggesting the involvement of sulfhydryl residues in the inhibition. 3-Phenyl-4-(phenylseleno) isoquinoline, which has documented pharmacological properties, had no toxicological effects on the parameters evaluated.

We found that elevated extracellular Pi strongly induced the expression of dentin matrix protein 1 (Dmp1) in osteoblasts and explored its underlying mechanism. Elevated extracellular Pi resulted in the phosphorylation of FRS2α, and an inhibitor against FGFR abolished the up-regulation of Dmp1 induced by elevated Pi. These results suggest the close relationship between the signaling evoked by elevated extracellular Pi and FGF/FGFR signaling.

Cytotoxic tiazolo[5,4b]quinolines are isosteres to amsacrine, yet their mechanism of action seems to be different, at least in relation to the unfolded protein response.

Various genetic mutations are associated with AML. FLT3/TKD mutations occur in 7% AML patients at residues D835 and I836 within the activation loop of the FLT3 protein, whereas mutations in exon 4 of IDH1 occur in ≈9% of Pakistani AML patients.

We reported our characterization of the sequence diversity of HFRS strains, 3D structure of Hantaan N protein, and B-cell epitopes on this molecule. We identified 20 amino acid sequence length peptide for development of geographic region-specific immunoassays like EIAs for antibody detection, monoclonal antibody development, and immunoblots (line immunoassay).

Finding useful candidate markers to differentiate ALD from NAFLD.

In this study, the SV40 large T antigen and human telomerase reverse transcriptase were employed to immortalize pooled equine chondrocytes through lentiviral vector mediated transduction either singly or on combination. Transformed chondrocytes proliferated stably over multiple passages, but resulted in significantly lower expression of chondrocyte specific collagen II mRNA (P < 0.0001) and up regulation of the hypertrophic marker collagen X (P < 0.0001) in three dimensional cultures whilst modulation of sox9 expression enabled control of hypetrophic characteristics.

PFK-P levels modulate the expression of ERK1 and ERK2. PFK-P levels interfere to cell responsiveness to drugs.

The Crohn's disease-associated mutation, R702W, in NOD2 lowers the activity the molecule by an unknown mechanism. We show that a NOD2 derived peptide containing the amino acid binds the ligand binding, regulatory domain, suggesting the residue is involved in autoinhibition. A synthetic peptide that competes with the interaction increases ligand-dependent NOD2 activity, showing that the receptor activity may be modulated using an allosteric regulator.

FDA approved proteasome inibitors such as bortezomib and carfilzomib have limited potency in triple negative breast cancer. Here we show that P-glygoprotein inhibitors such as verapamil and nicardipine can enhance the cytotoxic effects of proteasome inhibitors when used in combination to treat triple negative breast cancer cells.

FFAs suppress cell growth, enhance autophagy, and upregulate LOX-1 expression in vascular smooth muscle cells. FFAs trigger PI3K/Akt and MAPK activation that contributes to the LOX-1 upregulation. LOX-1 is potentially a therapeutic target for instability of atheromatous plaques.

Cells with increased osteogenic potential have higher levels of the H4K20 methyl transferase Suv420h2 compared to other methyl transferases. Loss of function analysis of Suv420h2 shows loss of H4K20 methylation and decreased expression of bone biomarkers and osteogenic transcription factors as well as decreased matrix mineralization during osteoblast differentiation. We conclude that Suv420h2 controls the H4K20 methylome of osteoblasts and is critical for normal progression of osteoblastogenesis.