Examining the Performance of Two Extraction Solvent Systems on Phenolic Constituents from U.S. Southeastern Blackberries.

Two common extraction solvent systems, namely acidified aqueous methanol and acidified aqueous acetone, were used to extract blackberry phenolics, and the antioxidant properties of the recovered extracts were compared. The crude extracts were fractionated into low- and high-molecular-weight phenolics by Sephadex LH-20 column chromatography. The hydrophilic-oxygen radical absorbance capacity (H-ORAC), ferric reducing antioxidant power (FRAP), and the cellular antioxidant activity (CAA) assays were employed as indices to assess antioxidant capacity of the extracts and their respective fractions.

The rise of affectivism.

Research over the past decades has demonstrated the explanatory power of emotions, feelings, motivations, moods, and other affective processes when trying to understand and predict how we think and behave. In this consensus article, we ask: has the increasingly recognized impact of affective phenomena ushered in a new era, the era of affectivism?

Identification of Novel Carbocyclic Pyrimidine Cyclic Dinucleotide STING Agonists for Antitumor Immunotherapy Using Systemic Intravenous Route.

Stimulator of Interferon Genes (STING) plays an important role in innate immunity by inducing type I interferon production upon infection with intracellular pathogens. STING activation can promote increased T-cell activation and inflammation in the tumor microenvironment, resulting in antitumor immunity. Natural and synthetic cyclic dinucleotides (CDNs) are known to activate STING, and several synthetic CDN molecules are being investigated in the clinic using an intratumoral administration route.

Discovery of TAK-981, a First-in-Class Inhibitor of SUMO-Activating Enzyme for the Treatment of Cancer.

SUMOylation is a reversible post-translational modification that regulates protein function through covalent attachment of small ubiquitin-like modifier (SUMO) proteins. The process of SUMOylating proteins involves an enzymatic cascade, the first step of which entails the activation of a SUMO protein through an ATP-dependent process catalyzed by SUMO-activating enzyme (SAE). Here, we describe the identification of TAK-981, a mechanism-based inhibitor of SAE which forms a SUMO-TAK-981 adduct as the inhibitory species within the enzyme catalytic site.

The cellular antioxidant and anti-glycation capacities of phenolics from Georgia peaches.

Plant-based polyphenolics have been reported to bestow health benefits when consumed, which are partially ascribed to their antioxidant activity. Yet, many current in vitro chemical assays to characterize antioxidant potential do not truly reflect the physiological properties of food antioxidants in vivo. The present study employed biological approaches, including a cellular antioxidant activity (CAA) and protein glycation assays, to offer an improved picture of antioxidant potential of phenolic extracts from Georgia peach cultivars.

Cellular evaluation of the antioxidant activity of U.S. Pecans [Carya illinoinensis (Wangenh.) K. Koch].

Clinical trials show an inverse relationship between the consumption of antioxidant-rich tree nuts and the development of chronic diseases. This study examined antioxidant efficacy of U.S.

Characterizing the phenolic constituents and antioxidant capacity of Georgia peaches.

Acetonic crude phenolic extracts of six Georgia peach cultivars were prepared and separated into low- and high-molecular-weight (LMW and HMW) fractions by Sephadex LH-20 column chromatography. Further characterization via RP-HPLC-ESI-MS identified the main phenolics as hydroxycinnamates, (+)-catechin, and proanthocyanidins with degrees of polymerization up to seven. The LMW phenolics of the commercial cultivar, 'July Prince', were further chromatographed and examined by RP-HPLC-ESI-MS.

A small-molecule inhibitor of the ubiquitin activating enzyme for cancer treatment.

The ubiquitin-proteasome system (UPS) comprises a network of enzymes that is responsible for maintaining cellular protein homeostasis. The therapeutic potential of this pathway has been validated by the clinical successes of a number of UPS modulators, including proteasome inhibitors and immunomodulatory imide drugs (IMiDs). Here we identified TAK-243 (formerly known as MLN7243) as a potent, mechanism-based small-molecule inhibitor of the ubiquitin activating enzyme (UAE), the primary mammalian E1 enzyme that regulates the ubiquitin conjugation cascade.

Modification of the cellular antioxidant activity (CAA) assay to study phenolic antioxidants in a Caco-2 cell line.

In vitro assays are widely used to analyze the antioxidant potential of compounds, but they cannot accurately predict antioxidant behavior in living systems. Cell-based assays, like the cellular antioxidant activity (CAA) assay, are gaining importance as they provide a biological perspective. When the CAA assay was employed to study phenolic antioxidants using hepatocarcinoma (HepG2) cells, quercetin showed antioxidant activity in HepG2 cells; 25 and 250μM quercetin reduced fluorescence by 17.

Using Physician-Level Emergency Department Utilization Reports to Address Avoidable Visits by Patients Managed by Pediatric Specialists.

Objectives: Emergency department (ED) utilization is a major driver of cost. Specialist physicians have an important role in addressing ED utilization, especially at tertiary medical centers that treat highly specialized patients. We analyzed if reporting of ED utilization to pediatric specialist physicians can decrease ED visits.

Effect of pecan phenolics on the release of nitric oxide from murine RAW 264.7 macrophage cells.

Inflammation is linked to numerous chronic disease states. Phenolic compounds have attracted attention because a number of these compounds possess anti-inflammatory properties. A phenolic crude extract was prepared from pecans and separated by Sephadex LH-20 column chromatography into low- and high-molecular-weight (LMW/HMW) fractions.

Emergency Department Utilization Report to Decrease Visits by Pediatric Gastroenterology Patients.

Background And Objectives: Emergency department (ED) utilization is a major driver of health care costs. Specialist physicians have an important role in addressing ED utilization, especially at highly specialized, academic medical centers. We sought to investigate whether reporting of ED utilization to specialist physicians can decrease ED visits.

Optimization of tetrahydronaphthalene inhibitors of Raf with selectivity over hERG.

Investigations of a biaryl ether scaffold identified tetrahydronaphthalene Raf inhibitors with good in vivo activity; however these compounds had affinity toward the hERG potassium channel. Herein we describe our work to eliminate this hERG activity via alteration of the substituents on the benzoic amide functionality. The resulting compounds have improved selectivity against the hERG channel, good pharmacokinetic properties and potently inhibit the Raf pathway in vivo.

Spontaneous rupture of unscarred uterus in a primigravida with preterm prelabour rupture of membranes.

Intrapartum uterine rupture is a true obstetrical emergency. Uterine rupture is associated with severe maternal and fetal morbidity and mortality. It is rare in the unscarred uterus of a primigravida.

Separation and characterization of phenolic compounds from U.S. pecans by liquid chromatography-tandem mass spectrometry.

The phenolic acids and proanthocyanidins (PACs) of pecans possess bioactive properties, which might be useful in retarding the onset of and ameliorating the status of certain chronic disease states. There is a general lack of information in the literature regarding such compounds, especially the PACs. Crude phenolic extracts pooled from eight commercially significant cultivars were selected based on their relatively high antioxidant capacities.

Inhibition of nonenzymatic protein glycation by pomegranate and other fruit juices.

The nonenzymatic glycation of proteins and the formation of advanced glycation endproducts in diabetes leads to the crosslinking of proteins and disease complications. Our study sought to demonstrate the effect of commonly consumed juices (pomegranate, cranberry, black cherry, pineapple, apple, and Concord grape) on the fructose-mediated glycation of albumin. Albumin glycation decreased by 98% in the presence of 10 μL of pomegranate juice/mL; other juices inhibited glycation by only 20%.

Inhibition of aromatase and α-amylase by flavonoids and proanthocyanidins from Sorghum bicolor bran extracts.

We compared the ability of simple flavonoids and proanthocyanidins in Sorghum bicolor bran extracts to inhibit enzymes in vitro. In particular, aromatase is a target for breast cancer therapy, and inhibition of α-amylase can reduce the glycemic effect of dietary starches. Proanthocyanidin-rich sumac sorghum bran extract inhibited α-amylase at a lower concentration (50% inhibitory concentration [IC₅₀]=1.

Design and optimization of potent and orally bioavailable tetrahydronaphthalene Raf inhibitors.

Inhibition of mutant B-Raf signaling, through either direct inhibition of the enzyme or inhibition of MEK, the direct substrate of Raf, has been demonstrated preclinically to inhibit tumor growth. Very recently, treatment of B-Raf mutant melanoma patients with a selective B-Raf inhibitor has resulted in promising preliminary evidence of antitumor activity. This article describes the design and optimization of tetrahydronaphthalene-derived compounds as potent inhibitors of the Raf pathway in vitro and in vivo.

Anti-inflammatory activity of select sorghum (Sorghum bicolor) brans.

The bran fractions of certain varieties of sorghum (Sorghum bicolor) grain are rich sources of phytochemicals and antioxidants. In this article, the anti-inflammatory actions of extracts of select sorghum brans were evaluated in two experimental inflammatory systems: (1) the release of cytokines by lipopolysaccharide-activated peripheral blood mononuclear cells and (2) 12-O-tetradecanoylphorbol acetate (TPA)-induced ear edema in mice. A 1:200 dilution of a 10% (wt/vol) ethanol extract of black sorghum bran significantly inhibited the secretion of the pro-inflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha.

Discovery and optimization of pyrazoline compounds as B-Raf inhibitors.

The discovery of novel pyrazoline derivatives as B-Raf (V600E) inhibitors is described in this report. Chemical modification of the pyrazoline scaffold led to the development of SAR and identified potent and selective inhibitors of B-Raf (V600E). Determination of the pharmacokinetic properties of selected inhibitors is also reported.

Antioxidant and anti-inflammatory activities of polyphenolics from Southeastern U.S. range blackberry cultivars.

The antioxidant and topical anti-inflammatory activities of low and high molecular weight phenolic fractions (LMPF and HMPF, respectively) isolated from three blackberry cultivars (i.e., Navaho, Kiowa, and Ouachita), bred to tolerate the warm and humid climatic conditions of the southeastern United States, were investigated by the in vitro ferric reducing antioxidant power (FRAP) assay and an in vivo mouse ear edema model.

Enhancement of resistance to coccidiosis and necrotic enteritis in broiler chickens by dietary muscadine pomace.

Muscadine pomace (MP), a by-product of the production of wine and juice from Vitis rotundifolia, was dried and tested in chickens for effects on primary resistance to coccidiosis, development of protective immunity after vaccination with live coccidia, and resistance to necrotic enteritis (NE) caused by the joint action of Clostridium perfringens and coccidia. To test primary resistance to coccidiosis, 2-wk-old chicks were given 2% or 5% MP in the diet and inoculated with Eimeria acervulina and E. maxima.

Inhibition of protein glycation by extracts of culinary herbs and spices.

We tested whether polyphenolic substances in extracts of commercial culinary herbs and spices would inhibit fructose-mediated protein glycation. Extracts of 24 herbs and spices from a local supermarket were tested for the ability to inhibit glycation of albumin. Dry samples were ground and extracted with 10 volumes of 50% ethanol, and total phenolic content and ferric reducing antioxidant potential (FRAP) were measured.