FoodComEx, a new chemical library for rare food-derived compounds

The lack of commercial standards for food-derived metabolites is a major limitation in nutritional metabolomics. FoodComEx (Food Compound Exchange) is a new chemical library initiated in the FoodBAll (Food Biomarkers Alliance) project (http://foodmetabolome.org) to facilitate the sharing of not easily accessible standards for food compounds and their human metabolites. FoodComEX (http://foodcomex.org/) will be a virtual library, with compounds stored in the laboratory where they have been isolated or synthesized. Version 1.0 will be an online catalog of pure compounds and reference materials (food extracts, biofluids from animals fed pure compounds, incubation media from in vitro systems to produce metabolites, etc.) made available by FoodBAll partners and associated collaborators. Each compound will appear with its elemental formula, monoisotopic mass, solubility, origin, purity, available quantity, storage conditions, stability, links to existing databases, type of spectral data available and contact details of the laboratory offering to share the standard. In the final version, which should be available at the end of 2016, spectral data (GC-MS, LC-MS, NMR, UV, IR) will be made searchable online. Anyone interested in one compound will directly contact the provider. A bilateral negotiation will define the terms of collaboration, within the rules defined in a charter of good practices. For example, the acquirer will have to share the spectral analyses acquired on his own analytical platform. This will continuously enrich the content of the chemical library. FoodComEx is a collaborative initiative widely open to new contributors and users. Anyone interested to contribute can contact u

Sofosbuvir-Based Direct-Acting Antiviral Therapies for Hcv in People Receiving Opioid Substitution Therapy: An Analysis of Phase 3 Studies

Background: Hepatitis C virus (HCV) direct-acting antiviral therapy is effective among people receiving opioid substitution therapy (OST), but studies are limited by small numbers of nongenotype 1 (GT1) patients. The aim of this study was to evaluate the treatment completion, adherence, SVR12, and safety of sofosbuvir-based therapies in HCV patients receiving and not receiving OST. Methods: Ten phase 3 studies of sofosbuvir-based regimens included ION (ledipasvir/sofosbuvir ± ribavirin for 8, 12, or 24 weeks in GT1), ASTRAL (sofosbuvir/velpatasvir for 12 weeks in GT1-6), and POLARIS (sofosbuvir/velpatasvir and sofosbuvir/velpatasvir/voxilaprevir in GT1-6). Patients with clinically significant drug use (last 12 months) or noncannabinoids detected at screening were ineligible. Results: Among 4743 patients, 4% (n = 194) were receiving OST (methadone; n = 113; buprenorphine, n = 75; other, n = 6). Compared with those not receiving OST (n = 4549), those receiving OST (n = 194) were younger (mean age, 48 vs 54), more often male (73% vs 61%), GT3 (38% vs 17%), treatment-naïve (78% vs 65%), and cirrhotic (36% vs 23%). Among those receiving and not receiving OST, there was no significant difference in treatment completion (97% vs 99%, P = .06), SVR12 (94% vs 97%, P = .06), relapse (0.5% vs 2.1%, P = .19), adverse events (78% vs 77%, P = .79), or serious adverse events (3.6% vs 2.4%, P = .24). There was no difference in SVR12 in patients with cirrhosis (99% vs 95%, P = .25) or those with G3 (95% vs 95%, P = .77) in those receiving OST. Among patients receiving OST, SVR12 was high among those receiving methadone (95%) and buprenorphine (96%). Conclusion: Sofosbuvir-based therapies are effective and safe in patients receiving OST.This work was supported by Gilead Sciences

Expansion of Luminal Progenitor Cells in the Aging Mouse and Human Prostate.

Aging is associated with loss of tissue mass and a decline in adult stem cell function in many tissues. In contrast, aging in the prostate is associated with growth-related diseases including benign prostatic hyperplasia (BPH). Surprisingly, the effects of aging on prostate epithelial cells have not been established. Here we find that organoid-forming progenitor activity of mouse prostate basal and luminal cells is maintained with age. This is caused by an age-related expansion of progenitor-like luminal cells that share features with human prostate luminal progenitor cells. The increase in luminal progenitor cells may contribute to greater risk for growth-related disease in the aging prostate. Importantly, we demonstrate expansion of human luminal progenitor cells in BPH. In summary, we define a Trop2+ luminal progenitor subset and identify an age-related shift in the luminal compartment of the mouse and human prostate epithelium

Expansion of Luminal Progenitor Cells in the Aging Mouse and Human Prostate.

Aging is associated with loss of tissue mass and a decline in adult stem cell function in many tissues. In contrast, aging in the prostate is associated with growth-related diseases including benign prostatic hyperplasia (BPH). Surprisingly, the effects of aging on prostate epithelial cells have not been established. Here we find that organoid-forming progenitor activity of mouse prostate basal and luminal cells is maintained with age. This is caused by an age-related expansion of progenitor-like luminal cells that share features with human prostate luminal progenitor cells. The increase in luminal progenitor cells may contribute to greater risk for growth-related disease in the aging prostate. Importantly, we demonstrate expansion of human luminal progenitor cells in BPH. In summary, we define a Trop2+ luminal progenitor subset and identify an age-related shift in the luminal compartment of the mouse and human prostate epithelium

A randomized, phase 1, placebo-controlled trial of APG-157 in oral cancer demonstrates systemic absorption and an inhibitory effect on cytokines and tumor-associated microbes

BACKGROUND: Although curcumin's effect on head and neck cancer has been studied in vitro and in vivo, to the authors' knowledge its efficacy is limited by poor systemic absorption from oral administration. APG-157 is a botanical drug containing multiple polyphenols, including curcumin, developed under the US Food and Drug Administration's Botanical Drug Development, that delivers the active components to oromucosal tissues near the tumor target. METHODS: A double-blind, randomized, placebo-controlled, phase 1 clinical trial was conducted with APG-157 in 13 normal subjects and 12 patients with oral cancer. Two doses, 100 mg or 200 mg, were delivered transorally every hour for 3 hours. Blood and saliva were collected before and 1 hour, 2 hours, 3 hours, and 24 hours after treatment. Electrocardiograms and blood tests did not demonstrate any toxicity. RESULTS: Treatment with APG-157 resulted in circulating concentrations of curcumin and analogs peaking at 3 hours with reduced IL-1β, IL-6, and IL-8 concentrations in the salivary supernatant fluid of patients with cancer. Salivary microbial flora analysis showed a reduction in Bacteroidetes species in cancer subjects. RNA and immunofluorescence analyses of tumor tissues of a subject demonstrated increased expression of genes associated with differentiation and T-cell recruitment to the tumor microenvironment. CONCLUSIONS: The results of the current study suggested that APG-157 could serve as a therapeutic drug in combination with immunotherapy. LAY SUMMARY: Curcumin has been shown to suppress tumor cells because of its antioxidant and anti-inflammatory properties. However, its effectiveness has been limited by poor absorption when delivered orally. Subjects with oral cancer were given oral APG-157, a botanical drug containing multiple polyphenols, including curcumin. Curcumin was found in the blood and in tumor tissues. Inflammatory markers and Bacteroides species were found to be decreased in the saliva, and immune T cells were increased in the tumor tissue. APG-157 is absorbed well, reduces inflammation, and attracts T cells to the tumor, suggesting its potential use in combination with immunotherapy drugs