Microbe-Derived Butyrate and Its Receptor, Free Fatty Acid Receptor 3, But Not Free Fatty Acid Receptor 2, Mitigate Neointimal Hyperplasia Susceptibility After Arterial Injury.

Background Arterial restenosis after vascular surgery is a common cause of midterm restenosis and treatment failure. Herein, we aim to investigate the role of microbe-derived butyrate, FFAR2 (free fatty acid receptor 2), and FFAR3 (free fatty acid receptor 3) in mitigating neointimal hyperplasia development in remodeling murine arteries after injury. Methods and Results C57BL/6 mice treated with oral vancomycin before unilateral femoral wire injury to deplete gut microbiota had significantly diminished serum and stool butyrate and more neointimal hyperplasia development after arterial injury, which was reversed by concomitant butyrate supplementation.

Carrageenan-Free Diet Shows Improved Glucose Tolerance and Insulin Signaling in Prediabetes: A Randomized, Pilot Clinical Trial.

Objectives: Carrageenan is well known to cause inflammation and is used in laboratory experiments to study mediators and treatments of inflammation. However, carrageenan is added to hundreds of processed foods to improve texture. Previous work indicated that low concentrations of carrageenan in drinking water caused marked glucose intolerance and insulin resistance in a mouse model.

Circulating plasma exosomes in obstructive sleep apnoea and reverse dipping blood pressure.

Background: Obstructive sleep apnoea (OSA) increases the risk of an abnormal nondipping 24 h blood pressure profile, an independent risk factor for cardiovascular disease (CVD). We examined differential exosomal microRNA (miRNA) expression in untreated OSA patients with normal dipping blood pressure (NDBP) and reverse dipping blood pressure (RDBP), an extreme form of nondipping, to understand the mechanisms underlying nondipping blood pressure in OSA.

Methods: 46 patients (15 RDBP 31 NDBP) matched for OSA severity (respiratory event index 32.

Mechanisms of Persistent Neurobiological Changes Following Adolescent Alcohol Exposure: NADIA Consortium Findings.

The Neurobiology of Adolescent Drinking in Adulthood (NADIA) Consortium has focused on the impact of adolescent binge drinking on brain development, particularly on effects that persist into adulthood. Adolescent binge drinking is common, and while many factors contribute to human brain development and alcohol use during adolescence, animal models are critical for understanding the specific consequences of alcohol exposure during this developmental period and the underlying mechanisms. Using adolescent intermittent ethanol (AIE) exposure models, NADIA investigators identified long-lasting AIE-induced changes in adult behavior that are consistent with observations in humans, such as increased alcohol drinking, increased anxiety (particularly social anxiety), increased impulsivity, reduced behavioral flexibility, impaired memory, disrupted sleep, and altered responses to alcohol.

Distinct Effects of Carrageenan and High-Fat Consumption on the Mechanisms of Insulin Resistance in Nonobese and Obese Models of Type 2 Diabetes.

Exposure to low concentration of the common food additive carrageenan (10 mg/L) for only six days led to glucose intolerance and insulin resistance in the C57BL/6J mouse. Longer exposure produced fasting hyperglycemia but with no increase in weight, in contrast to the HFD. Glucose intolerance was attributable to carrageenan-induced inflammation and to increased expression of GRB10.

CCL2 Induces the Production of β2 Adrenergic Receptors and Modifies Astrocytic Responses to Noradrenaline.

The decline in brain noradrenaline levels is associated with the progression of certain neurodegenerative diseases. This seems to be due, at least in part, to the ability of noradrenaline to limit glial activation and to reduce the damage associated with it. Our previous studies of the mechanisms involved in this process indicate that noradrenaline induces the production of the chemokine CCL2 in astrocytes.

Donepezil Reverses Dendritic Spine Morphology Adaptations and Fmr1 Epigenetic Modifications in Hippocampus of Adult Rats After Adolescent Alcohol Exposure.

Background: Adolescent intermittent ethanol (AIE) exposure produces persistent impairments in cholinergic and epigenetic signaling and alters markers of synapses in the hippocampal formation, effects that are thought to drive hippocampal dysfunction in adult rodents. Donepezil (Aricept), a cholinesterase inhibitor, is used clinically to ameliorate memory-related cognitive deficits. Given that donepezil also prevents morphological impairment in preclinical models of neuropsychiatric disorders, we investigated the ability of donepezil to reverse morphological and epigenetic adaptations in the hippocampus of adult rats exposed to AIE.

Cannabinoid-1 receptor neutral antagonist reduces binge-like alcohol consumption and alcohol-induced accumbal dopaminergic signaling.

Binge alcohol (ethanol) drinking is associated with profound adverse effects on our health and society. Rimonabant (SR141716A), a CB1 receptor inverse agonist, was previously shown to be effective for nicotine cessation and obesity. However, studies using rimonabant were discontinued as it was associated with an increased risk of depression and anxiety.

Lactobacillus acidophilus counteracts inhibition of NHE3 and DRA expression and alleviates diarrheal phenotype in mice infected with Citrobacter rodentium.

Impaired absorption of electrolytes is a hallmark of diarrhea associated with inflammation or enteric infections. Intestinal epithelial luminal membrane NHE3 (Na/H exchanger 3) and DRA (Down-Regulated in Adenoma; Cl/HCO exchanger) play key roles in mediating electroneutral NaCl absorption. We have previously shown decreased NHE3 and DRA function in response to short-term infection with enteropathogenic E coli (EPEC), a diarrheal pathogen.

Binge-Like Alcohol Exposure During Adolescence Disrupts Dopaminergic Neurotransmission in the Adult Prelimbic Cortex.

Repeated binge-like exposure to alcohol during adolescence has been reported to perturb prefrontal cortical development, yet the mechanisms underlying these effects are unknown. Here we report that adolescent intermittent ethanol exposure induces cellular and dopaminergic abnormalities in the adult prelimbic cortex (PrL-C). Exposing rats to alcohol during early-mid adolescence (PD28-42) increased the density of long/thin dendritic spines of layer 5 pyramidal neurons in the adult PrL-C.

A histone modification identifies a DNA element controlling slo BK channel gene expression in muscle.

The slo gene encodes the BK-type Ca(2+)-activated K(+) channels. In Drosophila, expression of slo is induced by organic solvent sedation (benzyl alcohol and ethanol), and this increase in neural slo expression contributes to the production of functional behavioral tolerance (inducible resistance) to these drugs. Within the slo promoter region, we observed that benzyl alcohol sedation produces a localized spike of histone acetylation over a 65-nucleotide (65-n) conserved DNA element called 55b.

Unintentional extraction of an endothelialized bare metal stent.

The extraction of a previously endothelialized stent has been rarely reported in the literature. We report a case of a patient with unstable angina due to in-stent restenosis. During percutaneous coronary intervention, a stent was inadvertently dislodged in the ostium of the right coronary artery.

Nanomedicines for chronic non-infectious arthritis: the clinician's perspective.

Rheumatoid arthritis (RA) and osteoarthritis (OA) are prevalent chronic health conditions. However, despite recent advances in medical therapeutics, their treatment still represents an unmet medical need because of safety and efficacy concerns with currently prescribed drugs. Accordingly, there is an urgent need to develop and test new drugs for RA and OA that selectively target inflamed joints thereby mitigating damage to healthy tissues.

Nanomedicines for chronic non-infectious arthritis: the clinician's perspective.

Rheumatoid arthritis (RA) and osteoarthritis (OA) are prevalent chronic health conditions. However, despite recent advances in medical therapeutics, their treatment still represents an unmet medical need because of safety and efficacy concerns with currently prescribed drugs. Accordingly, there is an urgent need to develop and test new drugs for RA and OA that selectively target inflamed joints thereby mitigating damage to healthy tissues.

Quality of life and psychosocial factors in African Americans with hypertensive chronic kidney disease.

Health-related quality of life (HRQOL) is poorly understood in patients with chronic kidney disease (CKD) prior to end-stage renal disease. The association between psychosocial measures and HRQOL has not been fully explored in CKD, especially in African Americans. We performed a cross-sectional analysis of HRQOL and its association with sociodemographic and psychosocial factors in African Americans with hypertensive CKD.

Molecular signature of kappa-carrageenan mimics chondroitin-4-sulfate and dermatan sulfate and enables interaction with arylsulfatase B.

The common food additive kappa-carrageenan (κ-CGN) is a sulfated polysaccharide that resembles chondroitin-4-sulfate (C4S) and dermatan sulfate (DS). All have a sulfate group on C4 of a glycoside (galactose for CGN and N-acetylgalactosamine for C4S), and the sulfate-bearing glycoside is linked in a β-1,4-configuration to an unsulfated, six-carbon sugar (galactose for CGN, glucuronate for C4S and iduronate for DS). The enzyme arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfate) is the highly selective enzyme that removes the four-sulfate group from the nonreducing terminus of C4S and DS, thereby regulating subsequent degradation.

TLR4-MyD88 signalling: a molecular target for alcohol actions.

Several studies implicate Toll-like receptors (TLRs) in alcohol-induced neuroinflammatory processes. The work reported by Wu et al., in this issue of the British Journal of Pharmacology, indicates that TLR4 along with its intracellular adaptor protein, MyD88, may play crucial roles in the acute actions of alcohol.

Transcriptional regulation of the intestinal luminal Na⁺ and Cl⁻ transporters.

The epithelial apical membrane Na+/H+ exchangers [NHE (sodium hydrogen exchanger)2 and NHE3] and Cl-/HCO3- exchangers [DRA (down-regulated in adenoma) and PAT-1 (putative anion transporter 1)] are key luminal membrane transporters involved in electroneutral NaCl absorption in the mammalian intestine. During the last decade, there has been a surge of studies focusing on the short-term regulation of these electrolyte transporters, particularly for NHE3 regulation. However, the long-term regulation of the electrolyte transporters, involving transcriptional mechanisms and transcription factors that govern their basal regulation or dysregulation in diseased states, has only now started to unfold with the cloning and characterization of their gene promoters.

Epidermal growth factor upregulates serotonin transporter in human intestinal epithelial cells via transcriptional mechanisms.

Serotonin transporter (SERT) regulates extracellular availability of serotonin and is a potential pharmacological target for gastrointestinal disorders. A decrease in SERT has been implicated in intestinal inflammatory and diarrheal disorders. However, little is known regarding regulation of SERT in the intestine.

The role of amygdaloid brain-derived neurotrophic factor, activity-regulated cytoskeleton-associated protein and dendritic spines in anxiety and alcoholism.

Innate anxiety appears to be a robust factor in the promotion of alcohol intake, possibly due to the anxiolytic effects of self-medication with alcohol. Brain-derived neurotrophic factor (BDNF) and its downstream target, activity-regulated cytoskeleton-associated (Arc) protein, play a role in the regulation of synaptic function and structure. In order to examine the role of the BDNF-Arc system and associated dendritic spines in the anxiolytic effects of ethanol, we investigated the effects of acute ethanol exposure on anxiety-like behaviors of alcohol-preferring (P) and -nonpreferring (NP) rats.

Genetic aspects of non-polypoid colorectal neoplasms.

Colorectal cancer is a heterogeneous disease arising through multiple possible pathways. Elucidating the genetic factors controlling molecular phenotype, morphology, histology, and prognosis of different tumor types continues to be a challenge. Non-polypoid colorectal neoplasms provide opportunities for ongoing study of their underlying genetic abnormalities and molecular phenotypes.