Cripto-1 as a Key Factor in Tumor Progression,Epithelial to Mesenchymal Transition and Cancer Stem Cells

Cripto-1 is an essential protein for human development that plays a key role in the early phase of gastrulation in the differentiation of an embryo as well as assists with wound healing processes. Importantly, Cripto-1 induces epithelial to mesenchymal transition to turn fixed epithelial cells into a more mobile mesenchymal phenotype through the downregulation of epithelial adhesion molecules such as E-cadherin, occludins, and claudins, and the upregulation of mesenchymal, mobile proteins, such as N-cadherin, Snail, and Slug. Consequently, Cripto-1’s role in inducing EMT to promote cell motility is beneficial in embryogenesis, but detrimental in the formation, progression and metastasis of malignant tumors. Indeed, Cripto-1 is found to be upregulated in most cancers, such as breast, lung, gastrointestinal, hepatic, renal, cervical, ovarian, prostate, and skin cancers. Through its role in EMT, Cripto-1 can remodel cancer cells to enable them to travel through the extracellular matrix as well as blood and lymphatic vessels to metastasize to different organs. Additionally, Cripto-1 promotes the survival of cancer stem cells, which can lead to relapse in cancer patients.     

Comprehensive Research on Past and Future Therapeutic Strategies Devoted to Treatment of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a rapidly debilitating fatal neurodegenerative disorder, causing muscle atrophy and weakness, which leads to paralysis and eventual death. ALS has a multifaceted nature affected by many pathological mechanisms, including oxidative stress (also via protein aggregation), mitochondrial dysfunction, glutamate-induced excitotoxicity, apoptosis, neuroinflammation, axonal degeneration, skeletal muscle deterioration and viruses. This complexity is a major obstacle in defeating ALS. At present, riluzole and edaravone are the only drugs that have passed clinical trials for the treatment of ALS, notwithstanding that they showed modest benefits in a limited population of ALS. A dextromethorphan hydrobromide and quinidine sulfate combination was also approved to treat pseudobulbar affect (PBA) in the course of ALS. Globally, there is a struggle to prevent or alleviate the symptoms of this neurodegenerative disease, including implementation of antisense oligonucleotides (ASOs), induced pluripotent stem cells (iPSCs), CRISPR-9/Cas technique, non-invasive brain stimulation (NIBS) or ALS-on-a-chip technology. Additionally, researchers have synthesized and screened new compounds to be effective in ALS beyond the drug repurposing strategy. Despite all these efforts, ALS treatment is largely limited to palliative care, and there is a strong need for new therapeutics to be developed. This review focuses on and discusses which therapeutic strategies have been followed so far and what can be done in the future for the treatment of ALS.     

Reversible signal abnormalities in the hippocampus and neocortex after prolonged seizures

PURPOSE: To investigate the phenomenon of reversible increased signal intensity of medial temporal lobe structures and cerebral neocortex seen on MR images of six patients with recent prolonged seizure activity. METHODS: After excluding patients with known causes of reversible signal abnormalities (such as hypertensive encephalopathy), we retrospectively reviewed the clinical findings and MR studies of six patients whose MR studies showed reversible signal abnormalities. MR pulse sequences included T2-weighted spin-echo coronal views or conventional short-tau inversion-recovery coronal images of the temporal lobes. RESULTS: All six MR studies showed increased signal intensity within the medial temporal lobe, including the hippocampus in five studies. All follow-up MR examinations showed partial or complete resolution of the hyperintensity within the medial temporal lobe and the neocortex. In one patient, results of a brain biopsy revealed severe cerebral cortical gliosis. Temporal lobectomy performed 4 years later showed moderate cortical gliosis and nonspecific hippocampal cell loss and gliosis. CONCLUSION: Significant hyperintensity within the temporal lobe is demonstrable on MR images after prolonged seizure activity, suggestive of seizure-induced edema or gliosis. Damage to medial temporal lobe structures by prolonged seizure activity indicates a possible mechanism of epileptogenic disorders.     

A new bath for the electrodeposition of aluminium. II. Kinetics and mechanism of the deposition and dissolution processes

The electrodeposition of aluminium was carried out successfully in AlCl₃-LiAlH₄/tetrahydrofuran-toluene solutions. The kinetic parameters controlling the cathodic deposition and anodic dissolution of aluminium were derived. The effect of the total concentration of aluminium and the molar ratio of AlCl₃ to LiAlH₄ on the current density-potential behaviour of the rotating disc aluminium electrode was also studied. A detailed mechanism for the electrode reactions was suggested.     

True Three-Dimensional Reconstruction (TTR) Application of Algorithm toward Full Utilization of Oblique Rays

The true three-dimensional reconstruction (TTR) algorithm previously proposed by the authors is extended to an algorithm with which full utilization of all the oblique rays is possible. Through this extended TTR (ETTR) algorithm, it is now possible not only to reconstruct an image of a larger object but also possible to obtain images which have substantially better signal-to-noise ratio. The basic TTR algorithm, as well as its extended version, will be discussed together with computer simulation results. In the appendixes, a new two-dimensional Fourier domain weighting function necessary for the implementation of the TTR and ETTR algorithms as well as the generality of the proposed TTR algorithm are discussed.     

A New Support Film for Cryo Electron Microscopy Protein Structure Analysis Based on Covalently Functionalized Graphene

Protein adsorption at the air–water interface is a serious problem in cryogenic electron microscopy (cryoEM) as it restricts particle orientations in the vitrified ice-film and promotes protein denaturation. To address this issue, the preparation of a graphene-based modified support film for coverage of conventional holey carbon transmission electron microscopy (TEM) grids is presented. The chemical modification of graphene sheets enables the universal covalent anchoring of unmodified proteins via inherent surface-exposed lysine or cysteine residues in a one-step reaction. Langmuir–Blodgett (LB) trough approach is applied for deposition of functionalized graphene sheets onto commercially available holey carbon TEM grids. The application of the modified TEM grids in single particle analysis (SPA) shows high protein binding to the surface of the graphene-based support film. Suitability for high resolution structure determination is confirmed by SPA of apoferritin. Prevention of protein denaturation at the air–water interface and improvement of particle orientations is shown using human 20S proteasome, demonstrating the potential of the support film for structural biology.     

In situ stabilization of chromium(VI) in polluted soils using organic ligands: the role of galacturonic, glucuronic and alginic acids

Laboratory batch sorption and column experiments were performed to investigate the role of organic ligands such as galacturonic, glucuronic and alginic acids (main constituents of bacterial exopolymeric substances (EPS)) on Cr(VI) uptake and transport in heterogeneous subsurface media. Our batch sorption experiments demonstrate the addition of galacturonic, glucuronic and alginic acids to soils enhances Cr(VI) uptake by soil at pH values <7.7 depending on the concentration of the ligand and pH used. The enhanced Cr(VI) uptake at pH values <7.7 may be explained through either the catalytic reduction of Cr(VI) to Cr(III) by the surface-bound organic matter/Fe oxides and/or the dissolved metal ions (e.g., Fe(III)) from the soil. On the other hand, organic ligands have no or little effect on Cr(VI) uptake under highly alkaline pH conditions since the catalytic Cr(VI) reduction decreases with increasing pH. Similarly, the results from column experiments show that, depending on the concentration of organic ligands, the Cr(VI) breakthrough curves were significantly retarded relative to the organic acid-free systems at pH 7.6. A significant portion of Cr(VI) initially added to the feed solution was not readily recoverable in the effluent, indicating Cr(VI) reduction in columns, most probably catalyzed by surface-bound metal-oxides (e.g., Fe oxides) or dissolved metal ions such as Fe(II; III). The overall results suggest that EPS constituents such as glucuronic, galacturonic and alginic acids may play a significant role on Cr(VI) stabilization in subsurface systems under acidic to slightly alkaline pH conditions.     

Synthesis,characterization, and voltammetric hydrogen peroxide sensing on novel monometallic (Ag,Co/MWCNT) and bimetallic (AgCo/MWCNT) alloy nanoparticles

Multiwall carbon nanotube supported (MWCNT) Ag, Co, and Ag-Co alloy nanocatalysts were synthesized at varying metal loadings by borohydride reduction methods without stabilizers to obtain enhanced hydrogen peroxide sensitivity. The resulting materials were characterized employing Scanning electron microscopy (SEM), Energy dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD). For electrochemical measurements carried out cyclic voltammetry (CV) and differential pulse voltammetry (DPV), glassy carbon electrode (GCE) was modified with Ag/MWCNT, Co/MWCNT, and Ag-Co/MWCNT alloy nanoparticles. Ag-Co/MWCNT/GCE exhibited the highest performance toward electrochemical oxidation of H₂O₂ in 0.1 M phosphate buffered solution (PBS). Furthermore, the sensitivity and the limit of detection values for Ag-Co/MWCNT/GCE were obtained as 57.14 µA cm^?2 mM^?1and 0.74 µM, respectively. However, the sensitivity values for Ag/MWCNT/GCE, and Co/MWCNT/GCE are 41.66 and 13.88 µA cm^?2 mM^?1, respectively. The LOD values were predicted as 1.84 µM for Ag/MWCNT/GCE and 3.3 µM for Co/MWCNT/GCE.

In addition, the interference experiment indicated that the Ag-Co/MWCNT alloy nanoparticles have good selectivity toward H₂O₂.