BH3 Mimetic Peptides: An Effective Strategy to Complement Anticancer Therapy.

Apoptosis, a natural process of programmed cell death, is a promising therapeutic target as the disruption of apoptosis evolves in many diseases including cancer. Several pieces of evidence indicate that errors in apoptotic pathways result in the imbalance between cell proliferation and death, allowing cells with genetic abnormalities to survive. The intrinsic and extrinsic pathways of apoptosis utilize different caspases to execute the event of cell death through the cleavage of hundreds of proteins.

Maternal dendritic cells influence fetal allograft response following murine in-utero hematopoietic stem cell transplantation.

Background: Intrauterine hematopoietic stem cell transplantation (IUT), potentially curative in congenital haematological disease, is often inhibited by deleterious immune responses to donor cells resulting in subtherapeutic donor cell chimerism (DCC). Microchimerism of maternal immune cells (MMc) trafficked into transplanted recipients across the placenta may directly influence donor-specific alloresponsiveness, limiting DCC. We hypothesized that dendritic cells (DC) among trafficked MMc influence the development of tolerogenic or immunogenic responses towards donor cells, and investigated if maternal DC-depletion reduced recipient alloresponsiveness and enhanced DCC.

Rapid Detection of Pathogenic Bacteria by the Naked Eye.

O157:H7 and are common pathogens. Gram-negative bacteria, such as , contain high concentrations of endogenous peroxidases, whereas Gram-positive bacteria, such as , possess abundant endogenous catalases. Colorless 3,5,3',5'-tetramethyl benzidine (TMB) changes to blue oxidized TMB in the presence of and a low concentration of HO (e.

Functional magnetic nanoparticle-based affinity probe for MALDI mass spectrometric detection of ricin B.

The use of lactosylated FeO magnetic nanoparticles (MNP@LAC) has been explored as affinity probes against ricin B based on galactose-ricin B binding interactions. Lactose was bound onto the surface of aminated MNPs through the Maillard reaction. The enrichment of ricin B took ~1 h by incubating MNP@LAC with samples under shaking at room temperature, followed by magnetic isolation.

Magnetic Graphene Oxide-Based Affinity Surface-Assisted Laser Desorption/Ionization Mass Spectrometry for Screening of Aflatoxin B1 from Complex Samples.

Aflatoxin B1 (AFB1), commonly found in agriculture products, has been considered as a carcinogen. Thus, to develop analytical methods that can be used to rapidly screen the presence of AFB1 in complex samples is important. Surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) uses inorganic materials as assisting materials to facilitate desorption/ionization of analytes.

Maternal microchimerism and cell-mediated immune-modulation enhance engraftment following semi-allogenic intrauterine transplantation.

Successful intrauterine hematopoietic cell transplantation (IUT) for congenital hemoglobinopathies is hampered by maternal alloresponsiveness. We investigate these interactions in semi-allogenic murine IUT. E14 fetuses (B6 females × BALB/c males) were each treated with 5E+6 maternal (B6) or paternal (BALB/c) bone marrow cells and serially monitored for chimerism (>1% engraftment), trafficked maternal immune cells, and immune responsiveness to donor cells.

Using lactosylated cysteine functionalized gold nanoparticles as colorimetric sensing probes for rapid detection of the ricin B chain.

A new colorimetric method that can be used to rapidly detect toxic ricin is demonstrated. Lactosylated cysteine-functionalized gold nanoparticles (Au@LACY NPs) were prepared by a one-pot reaction and employed as optical probes for determination of ricin B chain. It is found that the Au@LACY NPs undergo aggregation in the presence of ricin B chain.

Ultrathin, Strong, and Cell-Adhesive Agarose-Based Membranes Engineered as Substrates for Corneal Endothelial Cells.

We aimed to bioengineer a scaffold that can facilitate the transplantation of corneal endothelial cells (CEC), given the global shortage of cadaveric donor tissues. Although agarose (A) has outstanding biocompatibility and mechanical properties, it natively does not permit cell adhesion. In this study, agarose was modified with different attachment signals: GRGD (giving AR as product), lysine (AK), poly lysine (AP), and fish-derived gelatin (AG).

Thin peptide hydrogel membranes suitable as scaffolds for engineering layered biostructures.

A short tetramer peptide, Ac-IVKC, spontaneously formed a hydrogel in water. Disulfide bonds were introduced via hydrogen peroxide (HO)-assisted oxidation, resulting in (Ac-IVKC) dimers. The extent of disulfide bond formation and gel stiffness increased with the amount of HO used and 100% dimerization was achieved with 0.

Enhanced anticancer efficacy of histone deacetyl inhibitor, suberoylanilide hydroxamic acid, in combination with a phosphodiesterase inhibitor, pentoxifylline, in human cancer cell lines and in-vivo tumor xenografts.

Vorinostat [suberoylanilide hydroxamic acid (SAHA)], a histone deacetylase inhibitor, shows limited clinical activity against solid tumors when used alone. The methyl xanthine drug, pentoxifylline (PENT), has been described to have antitumor properties. The aim of this study was to look for the enhanced anticancer activities of both agents when used in combination at doses lower than their respective efficacy dose when used alone.

Prediction of drug-induced nephrotoxicity and injury mechanisms with human induced pluripotent stem cell-derived cells and machine learning methods.

The renal proximal tubule is a main target for drug-induced toxicity. The prediction of proximal tubular toxicity during drug development remains difficult. Any in vitro methods based on induced pluripotent stem cell-derived renal cells had not been developed, so far.

Synthesis of pyrazolylbisindoles over mesoporous Lewis acidic ZrTUD-1: Potential application in selective Cu(2+) colorimetric detection.

A series of pyrazolylbisindole (PBI) derivatives were prepared by simple condensation of indole and pyrazole aldehyde utilizing amorphous mesoporous ZrTUD-1 having predominant Lewis acid sites. The applicability of pyrazolylbisindolyl derivate as a colorimetric chemosensor with high selectivity toward Cu(2+) over other cations were tested. Among heavy and transition metal (HTM) ions in CH3CN solution, the probe only sensed Cu(2+) detectable by naked eye.

A novel pyrazole biscoumarin based chemosensors for the selective detection of Cu(2+) and Zn(2+) ions.

A novel chemosensor based on pyrazole biscoumarin molecule "4-hydroxy-3-((4-hydroxy-2-oxo-2H-chromen-3-yl)(1,3-diphenyl-1H-pyrazol-4-yl)methyl)-2H-chromen-2-one" (PBC) was synthesized by a simple method. The chemosensing properties of PBC towards transition metal ions like Cu(2+) and Zn(2+) by naked eye, UV-Visible and fluorescence spectroscopic methods were described. The PBC solution with Cu(2+) and Zn(2+) ion showed brown and blue colour respectively.

Polysulfone membranes coated with polymerized 3,4-dihydroxy-l-phenylalanine are a versatile and cost-effective synthetic substrate for defined long-term cultures of human pluripotent stem cells.

Clinical and industrial applications of human pluripotent stem cells (hPSC) require large amounts of cells that have been expanded under defined conditions. Labor-intensive techniques and ill-defined or expensive compounds and substrates are not applicable. Here we describe a chemically defined synthetic substrate consisting of polysulfone (PSF) membranes coated with polymerized 3,4-dihydroxy-l-phenylalanine (DOPA).

Buffalo cervico-vaginal fluid proteomics with special reference to estrous cycle: heat shock protein (HSP)-70 appears to be an estrus indicator.

Cervico-vaginal fluid (CVF) plays significant roles in coitus, sperm transport, and implantation. It is believed to be a good noninvasive biomarker for various diagnostic purposes. In this study, a comprehensive proteomic analysis of buffalo CVF was performed during the estrous cycle in order to document the protein expressions, utilizing SDS-PAGE, mass spectrometry, and immunoblot.

Identification of nephrotoxic compounds with embryonic stem-cell-derived human renal proximal tubular-like cells.

The kidney is a major target for drug-induced toxicity, and the renal proximal tubule is frequently affected. Nephrotoxicity is typically detected only late during drug development, and the nephrotoxic potential of newly approved drugs is often underestimated. A central problem is the lack of preclinical models with high predictivity.

Identification of p-cresol as an estrus-specific volatile in buffalo saliva: comparative docking analysis of buffalo OBP and β-lactoglobulin with p-cresol.

Assessment of salivary volatile compounds adopting gas chromatography-linked mass spectrometry (GC-MS) analysis revealed the presence of a total of 11 compounds in the buffalo saliva irrespective of the stages in the reproductive cycle. p-cresol was identified as an estrus-specific volatile compound in the saliva. In addition, modeling of odorant-binding protein (OBP) and β-lactoglobulin revealed that OBP is highly stable and has strong binding affinity with p-cresol.

Faecal chemical cues in water buffalo that facilitate estrus detection.

Chemo-signals are among the reliable non-invasive methods for estrus detection in mammals. Water buffalo is a silent heat animal and, hence, there is search for chemo-signals which would be effective non-invasive indicators of estrus state. We analyzed the faecal chemical cues during the estrous cycle in buffalo and to find the estrus-specific faecal volatile compounds adopting bull behavior assay.

A novel design of bioartificial kidneys with improved cell performance and haemocompatibility.

Treatment with bioartificial kidneys had beneficial effects in animal experiments and improved survival of critically ill patients with acute kidney injury in a Phase II clinical trial. However, a Phase II b clinical trial failed. This and other results suggested various problems with the current design of bioartificial kidneys.

Human embryonic stem cells differentiate into functional renal proximal tubular-like cells.

Renal cells are used in basic research, disease models, tissue engineering, drug screening, and in vitro toxicology. In order to provide a reliable source of human renal cells, we developed a protocol for the differentiation of human embryonic stem cells into renal epithelial cells. The differentiated stem cells expressed markers characteristic of renal proximal tubular cells and their precursors, whereas markers of other renal cell types were not expressed or expressed at low levels.

Perinuclear positioning of the inactive human cystic fibrosis gene depends on CTCF, A-type lamins and an active histone deacetylase.

The nuclear positioning of mammalian genes often correlates with their functional state. For instance, the human cystic fibrosis transmembrane conductance regulator (CFTR) gene associates with the nuclear periphery in its inactive state, but occupies interior positions when active. It is not understood how nuclear gene positioning is determined.

Bioanalytical method development, validation and quantification of flupirtine maleate in rat plasma by liquid chromatography-tandem mass spectrometry.

A simple, highly sensitive, precise and accurate high-performance liquid chromatographic (LCMSMS) method with mass detection was developed and validated for the rapid quantification of flupirtine (CAS 75507-68-5) in rat plasma samples. The chromatographic separation was achieved with a reverse phase column (4.6 x 50 mm, 5 microm) and the mobile phase consisted of cyanomethane and 5 mM ammonium formate buffer pH 4.

The use of a library of industrial materials to determine the nature of substrate-dependent performance of primary adherent human cells.

We developed a library of industrial materials, which can be applied to any adherent cell type for determining cell-material interactions. Bulk and surface chemistry as well as other material properties were characterized. The library covered broad ranges of various material properties.

The performance of primary human renal cells in hollow fiber bioreactors for bioartificial kidneys.

Bioartificial kidneys (BAKs) containing human primary renal proximal tubule cells (HPTCs) have been applied in clinical trials. The results were encouraging, but also showed that more research is required. Animal cells or cell lines are not suitable for clinical applications, but have been mainly used in studies on BAK development as large numbers of such cells could be easily obtained.