Lactobacillus bulgaricus OLL1181 activates the aryl hydrocarbon receptor pathway and inhibits colitis

Increasing evidence suggests that the aryl hydrocarbon receptor (AhR) pathway has an important role in the regulation of inflammatory responses. Most recently, we have shown that the activation of the AhR pathway by a potent AhR agonist inhibits the development of dextran sodium sulfate (DSS)-induced colitis, a model of human ulcerative colitis, by the induction of prostaglandin E2 (PGE2) in the large intestine. Because several strains of probiotic lactic acid bacteria have been reported to inhibit DSS-induced colitis by unidentified mechanisms, we hypothesized that particular strains of lactic acid bacterium might have the potential to activate the AhR pathway, thereby inhibiting DSS-induced colitis. This study investigated whether there are specific lactic acid bacterial strains that can activate the AhR pathway, and if so, whether this AhR-activating potential is associated with suppression of DSS-induced colitis. By using AhR signaling reporter cells, we found that Lactobacillus bulgaricus OLL1181 had the potential to activate the AhR pathway. OLL1181 also induced the mRNA expression of cytochrome P450 family 1A1 (CYP1A1), a target gene of the AhR pathway, in human colon cells, which was inhibited by the addition of an AhR antagonist, α-naphthoflavon (αNF). In addition, mice treated orally with OLL1181 showed an increase in CYP1A1 mRNA expression in the large intestine and amelioration of DSS-induced colitis. Thus, OLL1181 can induce activation of the intestinal AhR pathway and inhibit DSS-induced colitis in mice. This strain of lactic acid bacterium has therefore the potential to activate the AhR pathway, which may be able to suppress colitis

Prospective Study of Gefitinib Readministration After Chemotherapy in Patients With Advanced Non-Small-Cell Lung Cancer Who Previously Responded to Gefitinib

The present study was designed to prospectively evaluate the clinical efficacy of gefitinib readministration in patients with advanced non-small cell lung cancer who responded well to initial gefitinib, followed by cytotoxic chemotherapy. Twenty subjects were enrolled, and 3 and 6 patients achieved partial response and stable disease, respectively. These findings provide valuable information for the management of previous gefitinib responders. Introduction: Salvage treatment for acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitor in patients with non-small-cell lung cancer is a matter of clinical concern. Several retrospective reports have indicated the usefulness of epidermal growth factor receptor tyrosine kinase inhibitor readministration; however, there have been few prospective studies. Materials and Methods: This study was designed to prospectively evaluate the clinical efficacy of gefitinib readministration in patients with advanced or metastatic non-small-cell lung cancer who responded well to initial gefitinib treatment. The subjects received at least 1 regimen of cytotoxic chemotherapy after progressive disease with the initial gefitinib therapy. Gefitinib administration (250 mg/d, orally) was started after progressive disease with the previous chemotherapeutic regimen. The primary endpoint in the present study was the response rate. Results: Twenty patients were enrolled between April 2007 and May 2011. Three patients achieved partial response, and 6 showed stable disease. Thus, the overall response rate and disease control rate of gefitinib readministration were 15% (95% Cl, 3.21-37.9) and 45% (95% Cl, 23.1-68.5), respectively. Median progression-free survival and overall survival from the start of gefitinib readministration were 2.0 months (95% Cl, 0.9-3.1 months) and 12.0 months (95% Cl, 8.0-16.0 months), respectively. Conclusion: These results suggest that gefitinib readministration may be an option, albeit with a low response rate and short progression-free survival, for patients who responded well to initial gefitinib followed by systemic chemotherapy. These findings provide valuable information for the management of previous gefitinib responders.ArticleCLINICAL LUNG CANCER. 13(6):458-463 (2012)journal articl

Effects of acute aerobic exercise on arterial stiffness in transgender men

Testosterone replacement therapy (TRT) in transgender men (TM) results in side effects such as elevated triglycerides and increased arterial stiffness. Exercise may be useful to ameliorate such effects, but no studies have examined the effects of acute aerobic exercise in TM. This study aimed to investigate the effects of acute aerobic exercise on arterial stiffness in TM. Thirty-six participants were included, comprising 12 TM (duration of TRT: 57.4 ± 30.3 months), 12 males and 12 females. All participants performed acute aerobic exercise on a treadmill at 50% heart rate reserve for 30 min. Arterial stiffness as measured by brachial-ankle pulse wave velocity (baPWV) was measured before exercise (Pre), 30 min after exercise (Post30), and 60 min after exercise (Post60). Serum sex hormone levels, and serum lipid profile were determined only before exercise. Serum low-density lipoprotein cholesterol (LDL-C) levels before exercise were significantly higher in TM than in males or females (males: p < 0.01; females: p < 0.05). At all points, baPWV in TM was significantly higher than in females (p < 0.05) and significantly lower than in males (p < 0.05). However, when comparing changes in baPWV over time in each group, significant decreases in Post30 and Post60 were seen in males compared to Pre (both p < 0.05), but no significant change after aerobic exercise was seen in TM or females. These results suggest that acute aerobic exercise yield different effects in TM than in males, but is unlikely to reduce arterial stiffness in TM receiving TRT

Proteomics of appetite-regulating system influenced by menstrual cycle and intensive exercise in female athletes: a pilot study

Abstract Female athletes who endure intense training are at risk of developing the 'female athlete triad,' making energy intake management crucial. However, the fluctuations in estradiol and progesterone levels throughout the menstrual cycle present a challenge in maintaining consistent energy intake. This study aimed to uncover the underlying factors associated with appetite regulation linked to menstrual phases and exercise using proteomic approach. Five female athletes engaged in 60 min of bicycle exercise, followed by 90 min of rest, during both the follicular and luteal phases. Serum samples were collected before, during, and after exercise, and the serum proteome was analyzed using 2D-gel electrophoresis. A total of 511 spots were detected in the subjects' serum profiles, with significant decreases observed in haptoglobin during the luteal phase and complement component 3 during bicycle training. Unsupervised learning with a generalized estimating equation analysis showed that serum peptide YY (PYY), an appetite suppressor, significantly influenced the fluctuations of serum proteins induced by exercise (p < 0.05). Regression analysis demonstrated a positive correlation between PYY and serum IgM (R = 0.87), implying that the intestinal environment and the immune response in female athletes may contribute to appetite regulation

Effect of Green Tea Extract Ingestion on Fat Oxidation during Exercise in the Menstrual Cycle: A Pilot Study

In women, fat oxidation during exercise changes with the menstrual cycle. This study aimed to investigate the effect of green tea extract (GTE) ingestion on fat oxidation during exercise depending on the menstrual cycle phase. Ten women with regular menstrual cycles participated in this randomized, double-blind, crossover study. GTE or placebo was administered during the menstrual cycle&rsquo;s follicular phase (FP) and luteal phase (LP). Participants cycled for 30 min at 50% maximal workload, and a respiratory gas analysis was performed. Serum estradiol, progesterone, free fatty acid, plasma noradrenaline, blood glucose, and lactate concentrations were assessed before, during, and after the exercise. Fat oxidation, carbohydrate oxidation, and the respiratory exchange ratio (RER) were calculated using respiratory gas. Fat oxidation during the exercise was significantly higher in the FP than in the LP with the placebo (p &lt; 0.05) but did not differ between the phases with GTE. Carbohydrate oxidation, serum-free fatty acid, plasma noradrenaline, blood glucose, and lactate concentrations were not significantly different between the phases in either trial. Our results suggest that GTE ingestion improves the decrease in fat oxidation in the LP

Temperature Dependence of the Beating Frequency of hiPSC-CMs Using a MEMS Force Sensor

It is expected that human iPS cell-derived cardiomyocytes (hiPSC-CMs) can be used to treat serious heart diseases. However, the properties and functions of human adult cardiomyocytes and hiPSC-CMs, including cell maturation, differ. In this study, we focused on the temperature dependence of hiPSC-CMs by integrating the temperature regulation system into our sensor platform, which can directly and quantitatively measure their mechanical motion. We measured the beating frequency of hiPSC-CMs at different environmental temperatures and found that the beating frequency increased as the temperature increased. Although the rate at which the beating frequency increased with temperature varied, the temperature at which the beating stopped was relatively stable at approximately 20 °C. The stopping of beating at this temperature was stable, even in immature hiPSC-CMs, and was considered to be a primitive property of cardiomyocytes