bluuebunny/crossref_metadata_2025_split huggingface dataset:
Konjac glucomannan and inulin oligosaccharide attenuated the progression of colitic‐associated colon carcinogenesis and modulated immune response in mice
Authors: Wu Wen‐Tzu , Tsai Yi‐Ting , Chen Hsiao‐Ling 
Published: November 2023

The aim of this study was to determine effects of konjac glucomnanan and inulin oligosaccharide on tumor development and immune function using a colitis‐associated colon carcinogenesis mouse model. Male C57BL/6J (n = 36, six‐week‐old) mice were fed AIN‐93G diet and initially divided into vehicle control and AOM‐DSS groups. Mice were given an intraperitoneal injection of azoxymethane (AOM, 10 mg/kg BW) followed by three cycles of 1–1.5% (w/v) dextran sodium sulfate (DSS) in drinking water to induce colon cancer. The vehicle group was received 0.9% saline and distilled water instead. Three days after the last DSS cycle, the AOM‐DSS treated mice were randomly assigned to the following group: control (AIN‐93G diet), KGM (2%, w/w), or inulin (2%) for 9 weeks. The severity of adenocarcinoma, leukocyte phagocytic capacity, and spleen proinflammatory cytokines were determined. Results indicated that colonic adenocarcinoma occurred in all AOM‐DSS treated mice. Supplementation of KGM and inulin effectively reduced the extent of tumor invasion. AOM‐DSS treatment reduced the leukocyte phagocytic ability and increased the spleen interleukin‐1β (IL‐1β) and tumor necrosis factor‐α (TNF‐α) levels, which was partially reversed with KGM and inulin supplementation. This study suggested that supplementation of KGM or inulin (2%, w/w) during the cancer promotion period could reduce the progression of colitis‐associated colon carcinogenesis. The mechanisms mediating effects of these fibers may involve in the improvement of leukocyte phagocytic capacity and attenuation inflammatory cytokine in the spleen.Support or Funding InformationThis study was supported by the National Science Council Grant MOST‐103‐2320‐B‐040‐013‐MY3, Taipei, Taiwan.
α‐Asarone augments autophagophore elongation in oxysterol‐challenged macrophages
Authors: Park Sin‐Hye , Kang Young‐Hee 
Published: November 2023

Macrophage apoptosis plays a major role in the advanced atherosclerotic lesions, which is induced by several stimuli including endoplasmic reticulum (ER) stress and oxidative stress. In the recent studies, autophagic responses make cells escape from cellular apoptosis through promoting phagocytosis of misfolded proteins. α‐Asarone is isolated from Perilla frutescens, a traditional herb in the East‐Asia, and this compound possesses several effects on allergic inflammation. This study investigated whether α‐asarone alleviated macrophage apoptosis by promoting autophagic responses. To induce lipotoxicity in macrophages, this study treated 7β‐hydroxycholesterol in richly present in oxidized LDL. 7β‐Hydroxycholesterol induced cellular apoptosis by decreasing cell viability by ≈70% within 18 h, which were recovered by treating 10 μM α‐asarone. To induce ER stress by this oxysterol, the activation and induction of pancreatic ER kinase (PERK), translation initiation factor (eIF) 2α, activating transcription factor (ATF) 4 were determined. α‐Asarone down‐regulated the activation and induction of these ER stress‐related proteins. In addition, the oxysterol induced C/EBP homologous‐protein (CHOP) and DNA damage‐inducible protein (GADD34), which was dose‐dependently ameliorated by supplementing α‐asarone. Furthermore, to reveal a relationship between cellular apoptosis and autophagy, autophagy protein (ATG) 5 siRNA was employed in oxysterol‐challenged macrophages. The CHOP induction was up‐regulated in ATG5‐deleted macrophages free of autophagy, indicating that cellular apoptosis and autophagy was reciprocal in oxysterol‐challenged macrophages. The oxysterol enhanced the formation of ATG5/12/16L complex by instigating autophagy and increased LC3 induction for the autophagosome formation. α‐Asarone attenuated the formation autophagosomes through disturbing the formation of ATG5/12/16L complex and the LC3 conversion to LC3II for mature. Therefore, α‐asarone is a protective agent inhibiting atherosclerosis by ameliorating oxysterol‐mediated macrophage apoptosis and by augmenting autophagosome formation.Support or Funding InformationThis study was supported by Food, Agriculture, Forestry and Fisheries (112085‐03‐1‐SB010) and Brain Korea 21 plus program by Ministry of Education of Korea (22A20130012421).
Effects of Moderate Ethanol Consumption on Lipid Metabolism and Inflammation through Regulation of Gene Expression in Rats
Authors: Justice Meegan , Penprase Jerrold , Cintora Patricia , Erwin Danielle , Medrano Octavio , Brasser Susan M , Hong Mee Young 
Published: November 2023

Evidence supports a J or U‐shaped correlation with consumption of alcohol and cardiovascular disease (CVD) risk and suggests that light to moderate drinking as opposed to excessive consumption may provide some cardiovascular benefits. The present study examined the underlying mechanisms of how moderate alcohol consumption provides a protective effect against cardiovascular disease. Twenty‐four 109 day old, male Wistar rats were divided into a control group and a treatment group (n=12/group). The treatment group was administered a 20% v/v ethanol solution on alternate days for 12 weeks. There was no difference in body weight gain between the two groups, however, epididymal fat weight was lower in ethanol‐fed rats (P=0.030). Blood glucose was lower in the ethanol group compared to control (P=0.030). Total cholesterol levels (P=0.036) and LDL‐cholesterol levels (P=0.031) were also lower in the ethanol group. There was a significant reduction seen in the expression of hydroxymethylglutaryl‐coenzyme A reductase (Hmgcr) and sterol regulatory element‐binding protein‐2 (Srebp‐2) in the ethanol group (P=0.026 and P=0.034, respectively), suggesting that ethanol lowers cholesterol levels via downregulation of genes involved in cholesterol synthesis. Paraoxonase‐1 (Pon‐1), which is associated with inhibition of LDL‐cholesterol oxidation, was upregulated in the ethanol group (P=0.029). Cyclooxygenase‐2 (Cox‐2) and nuclear factor NF‐kappa‐B p65 subunit (Rela) gene expression was significantly decreased in ethanol‐treated rats (P=0.016 and P=0.047, respectively), indicating possible anti‐inflammatory effects. These findings suggest that moderate ethanol consumption may reduce the risk of CVD by reducing body fat, improving blood cholesterol and blood glucose, and modulation of gene expression involved in inflammation.Support or Funding InformationThis study was funded by NIH AA02329 and supported by San Diego State University N302L Advanced Nutrition Laboratory.
Daily consumption of a dark chocolate containing flavanols prevents genotoxicity in buccal epithelial cells and improves biochemical parameters related to cardiovascular risk factors in young adults
Authors: Leyva‐Soto Aldo , Chavez‐Santoscoy Rocio Alejandra , Lara‐Jacobo Linda Ramona , Re‐Araujo Denisse , Leal‐Orozco Alma Elia 
Published: November 2023

Epidemiological and medical anthropological investigations suggest that flavanol‐rich foods exert cardiovascular health benefits. Chocolate is a food that is known to be rich in flavonoids, the main flavonoids in chocolate is flavan‐3‐ol epicatechin. However, the bioavailability and the biological effects of the chocolate flavonoids are poorly understood. The objective was to quantify the effect of epicatechin ingested via dark chocolate on changes in biochemical parameters. Also to determine if the ingestion of dark chocolate rich in epicatechin exert anti‐gentoxic effect in buccal epithelial cells of young adults. Thirty apparently healthy men (20 to 30 years old) participated in a randomized, double‐blind, placebo‐controlled crossover trial during tree months. Consumption of dark chocolate or low‐flavanol chocolate (2 g) was daily ingested. Genotoxicity in buccal epithelial cells was determined by identify and quantify micronuclei in the exfoliated cells of oral mucosa in individuals before the intervention with chocolate, during the intervention (every mounth) and after the intervention. The concentration of glucose, cholesterol, HDL and LDL in plasma was determined before and after the ingestion of dark chocolate or low‐flavanol chocolate. The presence and amount of genotoxic damage was correlated with the main genotoxic factors (alcohol intake, smoking and obesity) and the ingestion of dark chocolate or low‐flavanol chocolate.Support or Funding InformationThis research was supported by the Research Chair Funds for Full Time Professors (2014) of Autonomous University of Baja California (UABC), program Number 3888. The authors would like to acknowledge Consejo Nacional de Ciencia y Tecnología (CONACYT) in Mexico.
Probiotic Supplements: Are They Alive?
Authors: Robbins Carrie Ann , Rogatzki Matt 
Published: November 2023

Over the past twenty years the industry of probiotics has grown as consumers have become more interested in the health benefits of “good” bacteria. These good bacteria have been shown clinically that they can positively affect mental health, irritable bowel syndrome, serum cholesterol and many other aspects of human health conditions. Due to the challenges of drying probiotic cultures, their viability has been brought into question. Under current legislation, dietary supplements are not required to be approved by the Food and Drug Administration (FDA) before they are marketed. The purpose of this study was to determine whether or not commercially available probiotics contain live microorganisms. Since Lactobacillus acidophilus are commonly sold in probiotic supplements, it was chosen to be the focus species of this experiment. Florajen Acidophilus, Renew Life's Vegetable Capsule Ultimate Flora, Bayer's TruBiotics, and Spring Valley's Acidophilus were tested for live bacteria. All samples used varied in price ranging from five dollars to nineteen dollars and contained varying amounts of bacterial cultures. A standard concentration of five hundred million cells per twenty mL was obtained and streaked on to plates of Tomato Juice Agar, as Lactobacillus acidophilus has been found to have enhanced growth on such media. Negative control plates were left unstreaked, while positive control plates were streaked by a stock culture of Lactobacillus acidophilus. Plates were incubated twelve to fifteen hours and observed for growth. Following the incubation periods, all positive control and experimental groups showed growth while negative control plates did not display growth. Techniques of drying probiotics can be quite challenging and lethal to bacterial cultures; however, the results of this study show promise that adequate numbers of bacteria can be delivered in the final product to consumers.Support or Funding InformationOffice of Undergraduate Research and Creative Endeavors: University of Wisconsin‐Platteville
The Stenotic Kidney in 2‐kidney 1‐clip Renovascular Hypertension is not Protected from Chronic Damage in CX3CL1 Deficient Mice
Authors: Grande Joseph Peter , Boyilla Rajendra , Osman Mazen , Hu Zeng , Kashyap Sonu 
Published: November 2023

CX3CR1 is a chemokine receptor widely expressed on inflammatory cells which recognizes CX3CL1 (fractalkine) a membrane bound chemokine that can function as an adhesion receptor. Blockade of CX3CR1 has been shown to reduce inflammation and chronic renal injury in a variety of models. We sought to determine whether CX3CR1 deficient mice are protected from chronic renal injury in experimental renal artery stenosis (RAS). RAS was established in CX3CR1 knockout (KO) and wild‐type C57BLK/6 mice (WT) through placement of a cuff on the right renal artery. Sham mice underwent manipulation of the right renal artery without placement of a cuff. As assessed by MRI, mean flow reduction was 65.3% in the WT mice and 66.5% in the KO mice (p=ns) subjected to RAS. Both KO and WT mice developed hypertension, which persisted throughout the 4 week study. KO and WT mice developed a similar degree of cardiac hypertrophy (166 mg WT, 172 mg KO, p=ns; 117 mg sham). Stenotic kidney weights were reduced to a similar extent in KO and WT mice (sham 148 mg, WT 83 mg, KO 53 mg) with compensatory hypertrophy of the contralateral kidney (sham 136 mg, WT 170 mg, KO 206 mg, p=0.0016 KO vs WT). The stenotic kidney of both KO and WT mice developed severe atrophy, characterized by flattening and simplification of tubular epithelium and influx of interstitial T cells and macrophages (32.8 % cortical surface area for WT and 76.4% cortical surface area for KO, p=0.01). The contralateral kidney was without significant histopathologic abnormality. We conclude that development of severe atrophy is not prevented in CX3CR1 KO mice, indicating that alternative pathways contribute to chronic renal damage in this model.Support or Funding InformationThis work is supported by NIH Grant R01 AI100911.
Ryanodine receptor‐dependent modulation of experimental autoimmune encephalomyelitis in mice
Authors: Osipchuk Natalia C. , Soulika Athena , Cruz‐Orengo Lillian , Allen Paul D. , Fomina Alla F. 
Published: November 2023

Experimental autoimmune encephalomyelitis (EAE) in mice is an established animal model of T cell‐mediated autoimmune disease. Pathological changes seen in EAE represent a stereotypic response of the CNS tissues to immunological priming following damage. EAE induced by immunizing wild‐type (WT) C57BL/6 mice with myelin oligodendrocyte glycoprotein peptide 35–55 (MOG35–55) results in CNS inflammation (macrophages and CD3+ T lymphocytes), demyelination, and axonal loss, which causes progressive development of neurological symptoms and impairment of motor functions.The strength and duration of cytosolic calcium signals defines T cell activation, differentiation, and immune response. Our previous studies performed in T cell cultures clearly demonstrated physiological significance of ryanodine receptors (RyRs), the endoplasmic reticulum calcium release channels, in T cell calcium signaling in vitro (Thakur et al, 2012, J Biol Chem, 287: 37233–44). Here we report that treatment of activated human T cells with RyR blockers suppresses T cell proliferation and reduces frequencies of T cell subtypes secreting proinflammatory cytokines. Furthermore, manipulation of RyR activity in vivo significantly affects the course of the EAE in mice. EAE was induced by immunizing adult WT C57BL/6 mice and mice carrying gain‐of‐function RyR type 1 R163C mutation on C57BL/6 background strain (RyR1 R163C mice) with MOG35–55. We found that RyR1 R163C heterozygosity is associated with the earlier disease onset and augmentation of neurological symptoms compared with WT mice. These data indicate that a “leaky” RyR1 amplifies autoimmune response in mice. We also found that mice injected daily with RyR1 inhibitor dantrolene beginning at the time of EAE induction, displayed significantly fewer neurological symptoms, reduced CNS inflammatory infiltrate and less axon damage compared to control EAE mice injected with vehicle alone. Withdrawing the dantrolene on day 30 post‐immunization was immediately followed by the development of neurological symptoms. No pro‐inflammatory infiltrate and/or axonal damage were detected in EAE mice treated with dantrolene. These data underscoring the key role of RyR1 in mounting the normal and pathological immune responses and indicate that RyR1 represents a powerful new tool for modulation of autoimmune responses.
Acute Tolerance to the Discriminative Stimulus Effects of Nicotine in Monkeys
Authors: Moerke Megan Jo , McMahon Lance 
Published: November 2023

Tolerance to the effects of nicotine, a major psychoactive component of tobacco, contributes to escalation in the frequency and quantity of tobacco use. However, mechanisms of tolerance to the effects of nicotine are not well understood. Here, drug discrimination was used to examine the rapid decrease in sensitivity to nicotine (i.e., acute tolerance), including its underlying receptor pharmacology and its relationship to nicotine pharmacokinetics. Rhesus monkeys (n=6) discriminated 0.032 mg/kg of nicotine base administered i.v. under an FR5 schedule of stimulus‐shock termination. Nicotine dose‐dependently increased drug‐lever responding; the ED50 value (95% confidence limits) of nicotine to produce discriminative stimulus effects was 0.012 (0.0077–0.020) mg/kg. The β2‐selective nicotinic acetylcholine receptor (nAChR) antagonist dihydro‐β‐erythroidine produced a 4.8‐fold rightward shift in the nicotine dose‐response function. Methyllycaconitine, an α7‐selective nAChR antagonist, up to 10 mg/kg did not antagonize the nicotine discriminative stimulus. The duration of the nicotine discriminative stimulus was less than 30 min; however, concentrations of nicotine measured in saliva were maximal (45–65 ng/ml) 10–30 min post‐injection. Pretreatment with nicotine (0.032 mg/kg i.v.) 30 min before re‐determination of sensitivity to the effects of nicotine resulted in a 3‐fold rightward shift in the dose‐response function. Firstly, these data suggest that the i.v. nicotine discriminative stimulus is mediated by β2‐containing, not α7‐containing, nAChRs. Secondly, decreased sensitivity to the discriminative stimulus effects of nicotine when preceded by an additional dose of nicotine 30 min earlier provides evidence of acute tolerance. That the peak concentrations of nicotine in saliva persist beyond the offset of its discriminative stimulus effects is also consistent with acute pharmacodynamic tolerance. Collectively, these results demonstrate that tolerance to the discriminative stimulus effects of nicotine can be produced by acute exposure to nicotine and suggest that the mechanism underlying acute tolerance may be related to rapid desensitization of β2‐containing nAChRs.Support or Funding InformationSupported by United States Public Health Service Grant DA 25267.
Effects of Chronic Treatment with Bupropion on Nicotine, Cocaine, and Nicotine + Cocaine Polydrug Self‐Administration
Authors: Kohut Stephen , Barkin Claire , Blough Bruce , Carroll F Ivy , Bergman Jack 
Published: November 2023

Clinical reports suggest that cocaine and nicotine are often used concurrently; however, medications to manage this form of polydrug addiction are lacking. Bupropion (Zyban), a dual monoamine (dopamine/norepinephrine) transport inhibitor, is a non‐nicotine‐based pharmacotherapy for smoking cessation that has been approved by the FDA and is currently used medicinally. The present study was conducted to investigate the potential utility of bupropion in managing nicotine + cocaine polydrug addiction by comparing its effectiveness in decreasing intravenous (IV) nicotine, cocaine, and nicotine + cocaine polydrug self‐administration. Adult rhesus monkeys responded under a second order (FR2 (VR16:S)) schedule of reinforcement for food or IV nicotine (0.001–0.0032 mg/kg), cocaine (0.0032–0.01 mg/kg), or nicotine (0.001–0.0032 mg/kg) + cocaine (0.0032–0.01 mg/kg) mixtures during four 1‐hr daily sessions. The effects of chronic treatment (5–10 days) with bupropion (1.0 – 1.8 mg/kg/hr, IV) on food‐ and drug‐maintained responding were then assessed. Consistent with our previous findings, combinations of nicotine (0.001 or 0.0032 mg/kg/inj) + a low dose of cocaine (0.0032 mg/kg/inj) were self‐administered to a greater extent than either drug alone. Results further indicate that consistent or significant alterations in responding for nicotine alone or cocaine alone were not observed during chronic treatment with bupropion; however, averaged data revealed dose‐dependent reductions in responding maintained by each combination of nicotine + cocaine studied. No consistent effects on food‐maintained responding were observed during bupropion treatment regimens. These results suggest that bupropion deserves further consideration for its potential use in the management of nicotine + cocaine polydrug addiction.Support or Funding InformationSupported by NIH DA026892, DA12970, DA019377, and DA039306
Comparing Cigarette Smoke Extract‐ and Nicotine‐Seeking Behavior after Exposure to Stress in Adolescent Rats
Authors: Gellner Candice 
Published: November 2023

The nearly 90% of people who begin smoking in their teens have a harder time quitting and are more likely to relapse. Therefore, it is important to understand relapse to smoking during this developmental period. To investigate the role of non‐nicotine constituents in relapse to smoking, we have established a model of intravenous self‐administration comparing cigarette smoke extract (CSE) to nicotine alone. Previous research in our lab has shown that adult male rats that self‐administer CSE extinguished more slowly and were more sensitive to stress‐induced reinstatement. We now test the hypothesis that adolescent rats will exhibit similar patterns of behavior. Adolescent rats, aged postnatal day (P) 25, were trained to lever press on a FR5TO20 schedule (1 food pellet per 5 lever presses with a time out period of 20 seconds). After rats reached the reinforced lever press threshold (R=35), they underwent surgery to implant a catheter in their right jugular vein. After three days recovery, rats (P35) began 1‐hour drug self‐administration sessions with nicotine or CSE (15 μg/kg/infusion nicotine content). Once rats reached stable responding for drug, drug was removed and drug‐seeking behavior was extinguished. Extinguished drug‐seeking behavior was reinstated with stress, cues, or a combination of stress and cues. Preliminary results suggest that baseline responding for CSE and nicotine groups is similar. When drug is removed, CSE and nicotine seeking rats display similar extinction rates. Adolescents also exhibit similar levels of stress‐ and stress+cue‐induced reinstatement of CSE and nicotine seeking behavior. Therefore, these preliminary findings suggest that the non‐nicotine constituents in cigarette smoke do not influence adolescent responding for drug, extinction or reinstatement of drug‐seeking behavior.Support or Funding InformationTRDRP Award #21RT‐0136; NIH Award #1R01DA040440‐01