Coffee consumption and mortality in colorectal cancer patients: does the co-existence of cardiometabolic disease matter?

Background: Although coffee consumption may have a U-shaped nonlinear relationship with all-cause mortality in colorectal cancer (CRC) patients, it is unclear whether this association could differ in the presence of prevalent cardiometabolic disease (CMD). Therefore, we assessed the association of coffee consumption with mortality in CRC patients stratified by CMD status at diagnosis.

Methods: We used data from a prospective cohort of 1,769 patients with stage I-III CRC.

Elucidation of the Active Agents in a West African Ground Herbal Medicine Formulation That Elicit Antimalarial Activities in In Vitro and In Vivo Models.

Agunmu (ground herbal medicine) is a form of West African traditional medicine consisting of a cocktail of herbs. The goal of this study is to evaluate a formulation of Agunmu made from , , , , and , sold in the open market and commonly used for the treatment of malaria by the locals, for its antimalarial effects and to determine the active principles that may contribute to the antimalarial effect. The ethanolic extract obtained from this formulation (Ag-Iba) was analyzed, using TLC, LC-MS, and Tandem-MS techniques, to determine its phytochemical properties.

IONIC NANOMEDICINE STRATEGY TO DEVELOP EFFECTIVE CHEMO-PTT COMBINATION CANCER THERAPEUTICS.

Herein, a detailed investigation of nanodrugs derived by combining a chemotherapy (chemo) and photothermal therapy (PTT) approaches to enhance chemo drug efficacy is presented. Tamoxifen and its metabolite; N-desmethyltamoxifen are the selected chemo drugs that were electrostatically attached with a PTT agent, NaIR820, via a metathesis approach to develop two different ionic material (IM)-based chemo-PTT drugs. Ionic nanomaterials (INMs) were synthesized using reprecipitation method, and these carrier- free nanoparticles were characterized in detail.

Small-molecule disruption of androgen receptor-dependent chromatin clusters.

Sustained androgen receptor (AR) signaling during relapse is a central driver of metastatic castration-resistant prostate cancer (mCRPC). Current AR antagonists, such as enzalutamide, fail to provide long-term benefit for the mCRPC patients who have dramatic increases in AR expression. Here, we report AR antagonists with efficacy in AR-overexpressing models.

A Novel Liver Cancer-Selective Histone Deacetylase Inhibitor Is Effective against Hepatocellular Carcinoma and Induces Durable Responses with Immunotherapy.

Hepatocellular carcinoma (HCC) progression is facilitated by gene-silencing chromatin histone hypoacetylation due to histone deacetylase (HDAC) activation. However, inhibiting HDACs-an effective treatment for lymphomas-has shown limited success in solid tumors. We report the discovery of a class of HDAC inhibitors (HDACi) that demonstrates exquisite selective cytotoxicity against human HCC cells.

Discovery and Folding Dynamics of a Fused Bicyclic Cysteine Knot Undecapeptide from the Marine Sponge .

We describe the discovery and structure of an undecapeptide natural product from a marine sponge, termed halichondamide A, that is morphed into a fused bicyclic ring topology via two disulfide bonds. Molecular dynamics simulations allow us to posit that the installation of one disulfide bond biases the intermediate peptide conformation and predisposes the formation of the second disulfide bond. The natural product was found to be mildly cytotoxic against liver and breast cancer cell lines.

Interrogating the Role of Endocytosis Pathway and Organelle Trafficking for Doxorubicin-Based Combination Ionic Nanomedicines.

We have studied the endocytic mechanisms that determine subcellular localization for three carrier-free chemotherapeutic-photothermal (chemo-PTT) combination ionic nanomedicines (INMs) composed of doxorubicin (DOX) and an near-infrared (NIR) dye (ICG, IR820, or IR783). This study aims to understand the cellular basis for previously published enhanced toxicity results of these combination nanomedicines toward MCF-7 breast cancer cells. The active transport mechanism of INMs, unlike free DOX, which is known to employ passive transport, was validated by conducting temperature-dependent cellular uptake of the drug in MCF-7 cells using confocal microscopy.

Development and validation of a sensitive LC-MS/MS assay of GT-14, a novel Gα2 inhibitor, in rat plasma, and its application in pharmacokinetic study.

A sensitive and selective LC-MS/MS method was developed and validated for the quantitation of a novel Gα2 inhibitor, GT-14, in rat plasma using a SCIEX 6500+ triple QUAD LC-MS system equipped with an ExionLC UHPLC unit. GT-14 (m/z 265.2 → 134.

A Novel Liver Cancer-Selective Histone Deacetylase Inhibitor Is Effective Against Hepatocellular Carcinoma and Induces Durable Responses with Immunotherapy.

Hepatocellular cancer (HCC) progression is facilitated by gene-silencing chromatin histone hypoacetylation due to histone deacetylases (HDACs) activation. However, inhibiting HDACs, an effective treatment for lymphomas, has shown limited success in solid tumors. We report the discovery of a class of HDAC inhibitors (HDACi) that demonstrates exquisite selective cytotoxicity against human HCC cells.

Doxorubicin-Based Ionic Nanomedicines for Combined Chemo-Phototherapy of Cancer.

Synergistic combination therapy approach offers lots of options for delivery of materials with anticancer properties, which is a very promising strategy to treat a variety of malignant lesions with enhanced therapeutic efficacy. The current study involves a detailed investigation of combination ionic nanomedicines where a chemotherapeutic drug is coupled with a photothermal agent to attain dual mechanisms (chemotherapy (chemo) and photothermal therapy (PTT)) to improve the drug's efficacy. An FDA-approved Doxorubicin hydrochloride (DOX·HCl) is electrostatically attached with a near-infrared cyanine dye (ICG, IR783, and IR820), which serves as a PTT drug using ionic liquid chemistry to develop three ionic material (IM)-based chemo-PTT drugs.

Coffee consumption is associated with a reduced risk of colorectal cancer recurrence and all-cause mortality.

Coffee consumption has been associated with a reduced risk of developing colorectal cancer (CRC). However, it is not clear whether coffee consumption is related to CRC progression. Hence, we assessed the association of coffee consumption with CRC recurrence and all-cause mortality using data from a prospective cohort study of 1719 stage I-III CRC patients in the Netherlands.

Gα2 Protein Inhibition Blocks Chemotherapy- and Anti-Androgen-Induced Prostate Cancer Cell Migration.

We have previously shown that heterotrimeric G-protein subunit alphai2 (Gα2) is essential for cell migration and invasion in prostate, ovarian and breast cancer cells, and novel small molecule inhibitors targeting Gα2 block its effects on migratory and invasive behavior. In this study, we have identified potent, metabolically stable, second generation Gα2 inhibitors which inhibit cell migration in prostate cancer cells. Recent studies have shown that chemotherapy can induce the cancer cells to migrate to distant sites to form metastases.

Cationic Porphyrin-Based Ionic Nanomedicines for Improved Photodynamic Therapy.

This study presents the synthesis and characterization of monosubstituted cationic porphyrin as a photodynamic therapeutic agent. Cationic porphyrin was converted into ionic materials by using a single-step ion exchange reaction. The small iodide counteranion was replaced with bulky BETI and IR783 anions to reduce aggregation and enhance the photodynamic effect of porphyrin.

Aflatoxin B1-induced dysfunction in male rats' reproductive indices were abated by Sorghum bicolor (L.Moench) hydrophobic fraction.

The burden of infertility distresses millions of families worldwide. The harmful effects of aflatoxin B1 (AFB1) on the reproductive system involve oxidative stress, culminating in inflammation and cellular apoptosis. The phytochemical in Sorghum bicolor is rich in antioxidants and anti-inflammatory activities.

The Hydrophobic Extract of (L. Moench) Enriched in Apigenin-Protected Rats against Aflatoxin B-Associated Hepatorenal Derangement.

Aflatoxin B1 (AFB) is a recalcitrant metabolite produced by fungi species, and due to its intoxications in animals and humans, it has been classified as a Group 1 carcinogen in humans. Preserving food products with sheath can minimise the contamination of agricultural products and avert ill health occasioned by exposure to AFB. The current study investigated the ameliorating effect of sheath hydrophobic extract (SBE-HP) enriched in Apigenin (API) on the hepatorenal tissues of rats exposed to AFB1.

Antiandrogen-Equipped Histone Deacetylase Inhibitors Selectively Inhibit Androgen Receptor (AR) and AR-Splice Variant (AR-SV) in Castration-Resistant Prostate Cancer (CRPC).

Background: Epigenetic modification influences androgen receptor (AR) activation, often resulting in prostate cancer (PCa) development and progression. Silencing histone-modifying enzymes (histone deacetylases-HDACs) either genetically or pharmacologically suppresses PCa proliferation in preclinical models of PCa; however, results from clinical studies were not encouraging. Similarly, PCa patients eventually become resistant to androgen ablation therapy (ADT).

The protective effect of 3-indolepropanoic acid on aflatoxin B1-induced systemic perturbation of the liver and kidney function in rats.

Aflatoxin B1 (AFB1) is known to derange the hepatorenal system by redox, DNA adduct formation and apoptotic networks. Endogenous 3-indole propionic acid (3-IPA) is a metabolite of tryptophan metabolism by gut microbiota that can protect against redox imbalance, inflammation and cellular lipid damage. We investigated the beneficial effect of 3-IPA against AFB1-mediated organ toxicity in male rats post 28 days of consecutive treatment.

Apigeninidin-enriched (L. Moench) extracts alleviate Aflatoxin B-induced dysregulation of male rat hypothalamic-reproductive axis.

We examined the protective effect of the apigeninidin (API)-enriched fraction from sheaths extracts (SBE-05, SBE-06, and SBE-07) against aflatoxin B (AFB)-induced dysregulation of male rat's reproductive system that may trigger infertility. Male rats (160 ± 12 g) were treated with AFB (50 µg/kg) along with 5 or 10 mg/kg of SBE-05, SBE-06, and SBE-07 for 28 days. Subsequently, we assessed the reproductive hormone-prolactin, FSH, LH, testosterone levels, and testicular function enzymes.

Apigeninidin-rich Sorghum bicolor (L. Moench) extracts suppress A549 cells proliferation and ameliorate toxicity of aflatoxin B1-mediated liver and kidney derangement in rats.

Sorghum bicolor plant has a high abundance of 3-deoxyanthocyanins, flavonoids and other polyphenol compounds that have been shown to offer numerous health benefits. Epidemiological studies have linked increased intake of S. bicolor to reduced risk of certain cancer types, including lung adenocarcinoma.

Inflammation, Fibrosis and Cancer: Mechanisms, Therapeutic Options and Challenges.

Uncontrolled inflammation is a salient factor in multiple chronic inflammatory diseases and cancers. In this review, we provided an in-depth analysis of the relationships and distinctions between uncontrolled inflammation, fibrosis and cancers, while emphasizing the challenges and opportunities of developing novel therapies for the treatment and/or management of these diseases. We described how drug delivery systems, combination therapy and the integration of tissue-targeted and/or pathways selective strategies could overcome the challenges of current agents for managing and/or treating chronic inflammatory diseases and cancers.

Synthetic methodology-enabled discovery of a tunable indole template for COX-1 inhibition and anti-cancer activity.

Establishing structure-activity relationships (SAR) for privileged pharmacophores, such as the indole scaffold, is a key step in the early stages of drug discovery. Herein, we report the synthesis and preliminary SAR studies on substituted 6-hydroxyindole-7-carboxylates as a tunable framework for COX inhibition and anti-cancer activity. To facilitate the SAR discovery, a modular synthetic methodology was employed which enabled the synthesis of the substituted indoles.

Caffeic acid mitigates aflatoxin B1-mediated toxicity in the male rat reproductive system by modulating inflammatory and apoptotic responses, testicular function, and the redox-regulatory systems.

Aflatoxin B1 (AFB ) is a toxic metabolite of public health concern. The present study investigates the protective effects of caffeic acid (CA) against AFB -induced oxidative stress, inflammation, and apoptosis in the hypothalamus, epididymis, and testis of male rats. Five experimental rat cohorts (n = 6) were treated per os for 28 consecutive days as follows: Control (Corn oil 2 ml/kg body weight), AFB1 alone (50μg/kg), CA alone (40 mg/kg) and the co-treated rat cohorts (AFB : 50μg/kg + CA1: 20 or 40 mg/kg).

Caffeic acid protects against DNA damage, oxidative and inflammatory mediated toxicities, and upregulated caspases activation in the hepatorenal system of rats treated with aflatoxin B.

Aflatoxicosis can induce largescale toxicities in predisposed populations. Food fortification with adequate antioxidant sources may reduce the toxic burden from aflatoxicosis. We examined the individual and combined effect of Caffeic acid (CA) on the aflatoxin B (AFB)-induced hepatic and renal injury in male rats.

Indole-3-propionic acid mitigates chlorpyrifos-mediated neurotoxicity by modulating cholinergic and redox-regulatory systems, inflammatory stress, apoptotic responses and DNA damage in rats.

This study probed the neuroprotective influence of indole-3-propionic acid (IPA) in rats exposed to chlorpyrifos (CPF) alone at 5 mg/kg body weight or co-administered with IPA at 12.5 and 25 mg/kg for 14 days. Behavioral data indicated that IPA significantly (p < 0.

Decrease in reproductive dysfunction using aflatoxin B1 exposure: a treatment with 3-indolepropionic acid in albino Wistar rat.

We assessed the individual and combined consequence of 3-indolepropionic acid on aflatoxin B1-induced reproductive toxicity in rats. The experimental cohorts were dosed for four consecutive weeks with aflatoxin B1 (50 μg/kg), 3-indolepropionic acid (50 mg/kg), and both (aflatoxin B1: 50 μg/kg + 3-indolepropionic acid: 25 or 50 mg/kg), and the untreated control. Following sacrifice, biomarkers of testicular, epididymal and hypothalamic oxidative status, lipid peroxidation, reactive oxygen and nitrogen species, nitric oxide levels and myeloperoxidase activity were determined.