DipHe

Platinum-based compounds remain a well-established chemotherapy for cancer treatment despite their adverse effects which substantially restrict the therapeutic windows of the drugs. Both the cell type-specific toxicity and the clinical responsiveness of tumors have been associated with mechanisms that alter drug entry and export. We sought to identify pharmacological agents that promote cisplatin (CP) efficacy by augmenting the levels of drug-induced DNA lesions in malignant cells and simultaneously protecting normal tissues from accumulating such damage and from functional loss...

Trypsin and thrombin, structurally similar serine proteases, recognize different substrates; thrombin cleaves after Arg whereas trypsin after Lys/Arg. Both recognize basic substrate headgroups via Asp189 at the bottom of the S1-pocket. By crystallography and ITC, we studied a series of D-Phe/-D-DiPhe-Pro-(amino)pyridines. Identical ligand pairs show the same binding poses. Surprisingly, one ligand binds to trypsin in protonated, to thrombin in unprotonated state at P1 along with differences in the residual solvation pattern...

BACKGROUND: A dramatic improvement in obliteration rates of large, wide-necked aneurysms has been observed after the FDA approved the Pipeline Embolization Device (PED) in 2011. OBJECTIVE: To assess the predictors of complications, morbidity, and unfavorable outcomes in a large cohort of patients with aneurysms treated with PED. METHODS: A retrospective chart review of a prospectively maintained database for subjects treated with flow diversion from 2010 to 2019...

A copper-catalyzed regio-, diastereo-, and enantioselective decarboxylative ring-opening [3 + 2] annulation of tertiary propargylic carbamates with γ-butenolides for the synthesis of optically active pyrrolidinones has been realized. The reaction proceeded through regioselective α-attack of γ-butenolide and generated highly congested vicinal tertiary and all-carbon quaternary stereocenters in pyrrolidinone scaffolds, featuring high stereoselective induction and broad functional group tolerance. Critical to the successful development of this method was the employment of copper catalysis in concert with a diPh-Pybox ligand...

A novel oxidation system in which magnesium nitrate [Mg(NO3 )2 ] is used as an oxidant in the presence of diphe-nylphosphine oxide [HP(O)Ph2 ] permits the C(sp3 )-H hydroxylation of fluorenes, oxindoles, and benzofuranones. This method features high efficiency, good functional group tolerance, and operational simplicity. The synthetic utility is highlighted by further transformations to valuable organic materials.

Preclinical assays play a key role in research in research on the neurobiology of pain and the development of novel analgesics. Drugs available for the treatment of inflammatory pain are not fully effective and show adverse effects. Thus, we investigated the antinociceptive, anti-inflammatory and anti-hyperalgesic effects of bis(3-amino-2-pyridine) diselenide (BAPD), a new analgesic drug prototype. BAPD effects were investigated using nociception models induced by chemical (glutamate), immunologic (Freund's Complete Adjuvant - CFA) and thermal stimuli in Swiss mice...

An enantio- and diastereoselective syntheses of 1, 3-disubstituted isoindolines and tetrahydroisoquinolines via CuI -Pybox-diPh catalyzed one-pot imination-alkynylation-aza-Michael sequence has been reported. The three-component reaction produces one C-C and two C-N bonds sequentially with high yield (up to 92%), enantioselectivity (up to 99%), and diastereoselectivity (up to 9:1) in a single operation. Furthermore, the synthetic utility of the product has been demonstrated by LiAlH4 reduction of ester and hydrogenation of alkyne functionality without losing the stereoselectivity...

Background Pipeline embolization devices (PEDs) are used for endovascular treatment of cerebral aneurysms but can be associated with delayed ipsilateral intraparenchymal hemorrhage (DIPH). Changes in intracranial hemodynamics after PED are poorly understood. Objective Here, we assess hemodynamic changes after PED in patients and compare these changes in patients with and without DIPH (DIPH+ and DIPH-). Methods Records of patients with distal internal carotid artery (ICA) aneurysms treated with PED at our institution between 2012 and 2017 were retrospectively reviewed...

Cellulose nanocrystals (CNCs) have emerged as promising candidates for a number of bio-applications. Surface modification of CNCs continues to gain significant research interest as it imparts new properties to the surface of the nanocrystals for the design of multifunctional CNCs-based materials. A small chemical surface modification can potentially lead to drastic behavioral changes of cell-material interactions thereby affecting the intended bio-application. In this work, unmodified CNCs were covalently decorated with four different organic moieties such as a diaminobutane fragment, a cyclic oligosaccharide ( β -cyclodextrin), a thermoresponsive polymer (poly[ N -isopropylacrylamide]), and a cationic aminomethacrylamide-based polymer using different synthetic covalent methods...

Acquisition of the dissolution profiles of more than single active ingredient in a multi-analyte pharmaceutical formulation is a mandatory manufacturing practice that is dominated by utilization of the off-line separation-based chromatographic methods. This contribution adopts a new "Double-Track" approach with the ultimate goal of advancing the in-line potentiometric sensors to their most effective applicability for simultaneous acquisition of the dissolution profiles of two active ingredients in a binary pharmaceutical formulation...

OBJECTIVE: Pipeline Embolization Devices (PED) are commonly used for endovascular treatment of cerebral aneurysms but can be associated with delayed ipsilateral intraparenchymal hemorrhage (DIPH). The role that altered intracranial hemodynamics may play in the pathophysiology of DIPH is poorly understood. We assess middle cerebral artery (MCA) flow velocity changes after PED deployment. MATERIALS AND METHODS: Patients with aneurysms located proximal to the internal carotid artery terminus treated with PED at our institution between 2015 and 2016 were retrospectively reviewed...

The ability of the bis(imidazolyl)ketone ligand BMdiPh IK (bis(1-methyl-4,5-diphenylimidazolyl)ketone) to function as a redox active ligand has been investigated. The reduction of [M(BMdiPh IK)Cl2 ] (M = Fe and Zn) complexes resulted in a pinacol-type coupling to form dinuclear complexes featuring very weak and abnormally elongated C-C bonds (1.729(5) and 1.708(3) Å for Fe and Zn, respectively). Oxidation of these complexes using ferrocenium in the presence of Cl- ions regenerated the original [M(BMdiPh IK)Cl2 ] complexes, showing the reversibility of the coupling process...

The catalyst system of Pd(TFA)2 /(S,S)-diPh-pyrox is reported to promote the highly efficient enantioselective oxidative cascade cyclization of alkene-tethered aliphatic acrylamides under mild aerobic conditions. A series of pyrrolizidine derivatives have been synthesized in good yield and excellent enantioselectivity. Deuterium-labeling experiments have revealed that the reaction proceeded through an anti-aminopalladation (anti-AP) pathway with high selectivity. The transition states for the anti-AP step have been calculated to account for the observed enantioselectivity...

Low-resource settings often have limited use of local data for health system planning and decision-making. To promote local data use for decision-making and priority setting, we propose an adapted framework: a data-informed platform for health (DIPH) aimed at guiding coordination, bringing together key data from the public and private sectors on inputs and processes. In working to transform this framework from a concept to a health systems initiative, we undertook a series of implementation research activities including background assessment, testing and scaling up of the intervention...

Praziquantel (PZQ) is prescribed as a racemic mixture (racemic-PZQ, rac-PZQ), which is composed of (R)-PZQ and (S)-PZQ. In this work, the cytotoxicity of rac-PZQ and its two enantiomers (R)-PZQ and (S)-PZQ on eight cell lines (L-02, HepG2, prf-plc-5, SH-SY5Y, HUVEC, A549, HCT-15, Raw264.7) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphe-nyltetrazolium bromide and lactate dehydrogenase assays. The morphology of apoptotic cells was studied by fluorescence microscope using Hoechst 33342 staining, and the cytotoxicity of the compounds was also tested by lactate dehydrogenase assay...

A unified approach for the asymmetric syntheses of medicinally important isoindolinones (S)-PD 172938 and (R)-JM 1232 has been accomplished via a Cu(I)-PYBOX-diPh catalyzed highly enantioselective (up to 99% ee) alkynylation/lactamization sequence in a one-pot fashion. The overall sequence involves one C-C and two C-N bond forming events in one pot starting from inexpensive starting material in ambient reaction conditions.

Novel chitosan-based nanofibrous composite materials containing different amounts of the photosensitizer Photosens were obtained by electrospinning and were characterized by scanning electron microscopy and by confocal laser scanning microscopy. The release of Photosens from the materials was investigated in water and in phosphate-buffered saline. A noncancerous (MC3T3-E1 murine osteoblasts) and a cancerous [T-47D (mammary gland)] cell line were cultivated on Photosens-containing scaffolds, and cell growth and metabolic activity were examined by confocal laser scanning microscopy and by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphe-nyltetrazolium bromide assay, respectively...

INTRODUCTION: Delayed aneurysm rupture and delayed intraparenchymal hemorrhages (DIPH) are poorly understood and often fatal complications of flow diversion (FD) for intracranial aneurysms. The purpose of this study was to identify risk factors for these complications. METHODS: We performed a systematic review on post-FD delayed aneurysm rupture and DIPH. For each reported case, we collected the following information: aneurysm location, size and rupture status, type of flow diverter used, timing of the hemorrhage, and neurological outcome...

An unprecedented Cu(I)-pybox-diPh-catalyzed highly enantioselective (up to >99% ee) alkynylation/lactamization cascade has been developed as a general catalytic system for the synthesis of diversely substituted isoindolinones of immense biological importance. The cascade effects one C-C and two C-N bond-forming events in one reaction vessel under operationally simple, additive-free reaction conditions in good to excellent yields. The methodology was further extended to the synthesis of tetrahydroisoquinoline scaffolds common to several biologically active natural products in a two-step sequence with remarkable selectivity (up to 94% ee)...

To investigate the role of RAD001 in the reversing of drug resistance of SGC7901/DDP, we cultured SGC7901/DDP cells with different groups of drugs (RAD001, cisplatin (DDP) alone, or the combination of RAD001 and DDP); after that, we detected the drug sensitivity, cell apoptosis, and levels of P-gp, MRP1, and survivin in the cells of SGC7901/DDP by MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphe-nyltetrazolium bromide) assay, flow cytometry, immunohistochemical analysis, and Western blot analysis. There was no significant difference between DDP 2...