Plasma Oxidative State Induced by Exercise in Young Heat-Not-Burn Cigarette Users.

INTRODUCTION: Oxidative state, a risk factor for several diseases, is increased by habitual conventional cigarette (CC) smoking. Reports have demonstrated that heat-not-burn cigarettes (HNBCs), which have recently become popular among smokers, generate less oxidative state than CC in smokers with a long smoking history. However, no previous study has examined oxidative state in young HNBC users. Previously, we reported that exercise induces a greater oxidative state in young CC smokers than in never-smokers of similar age, but there was no difference in resting oxidative state. This study aimed to clarify the resting and exercise-induced oxidative states in young HNBC users, compared with those in never-smokers and CC users of similar age. METHODS: Healthy young never-smokers, HNBC users, and CC users were recruited, and they underwent the Wingate anaerobic test. Blood samples were collected before and after exercise, and the plasma hydroperoxide concentration, a marker of oxidative state, was measured. RESULTS: No significant differences in pre-exercise plasma hydroperoxide concentrations were detected among never-smokers, HNBC users, and CC users (n = 10 each). Plasma hydroperoxide concentration was significantly increased after exercise in all participants. The exercise induced a significant increase in plasma hydroperoxide concentration in HNBC users compared with that in never-smokers (p < .005), but it was significantly decreased compared with that in CC users (p < .01). CONCLUSIONS: The use of HNBC increased exercise-induced plasma oxidative state compared with that in never-smokers, indicating that HNBC may lead to the risk of oxidative damage. IMPLICATIONS: This study, for the first time, reports exercise-induced oxidative state in young HNBC users compared with never-smokers and CC users. The exercise-induced oxidative state in HNBC users was higher than that in never-smokers and lower than that in CC users. Our study suggests that the use of HNBCs increases the risk of acute oxidative damage.

Discovery of natural TRPA1 activators through pharmacophore-based virtual screening and a biological assay.

Transient receptor potential cation channel subfamily A member 1 (TRPA1), a member of the transient receptor potential family, detects a wide range of environmental stimuli, such as low temperature, abnormal pH, and reactive irritants. TRPA1 is of great interest as a target protein in fields related to pharmaceuticals and foods. In this study, a library of natural products was explored to identify TRPA1 activators by pharmacophore screening of known TRPA1 agonists and biological assays for agonist activity. The study identified six natural compounds as novel TRPA1 agonists. The discovery of these compounds may prove useful in elucidating the TRPA1 activation mechanism.

Twenty-four-hour ambulatory oximetry monitoring in a patient with idiopathic pulmonary fibrosis for assisting in the discharge instruction on activities of daily living: a case report.

[Purpose] Patients with idiopathic pulmonary fibrosis (IPF) often develop remarkable exercise-induced hypoxemia and are hospitalized for management. The pre-discharge management of activities of daily living (ADL) should determine the amount of exercise-induced hypoxemia permitted during daily activities and inform concrete instructions based on these results. This clinical report aimed to promote 24-hour ambulatory oximetry monitoring in a patient with IPF to guide the pre-discharge management of ADL. [Participant and Methods] Our patient was a 67-year-old male with IPF. He was hospitalized and scheduled to be discharged after introduction of home oxygen therapy. Prior to discharge, we conducted a 24-hour ambulatory oximetry monitoring in the patient's home. We administered instructions on ADL based on these results. Furthermore, 1 day after discharge, we monitored his oxygen saturation level during ADL in his home. [Results] During the pre-discharge monitoring, the patient experienced hypoxemia during bathing, with a minimum oxygen saturation (SpO2) level of 87% and SpO2 level of <90% for 14.3% of the time. The patient was instructed on bathing by a physical therapist before discharge; this led to decreased desaturation, as the patient's SpO2 was <90% for 7.7% of the time. [Conclusion] Twenty-four-hour ambulatory oximetry monitoring is effective in guiding the pre-discharge management of ADL in the home with home oxygen therapy for patients with IPF.

Identification of a new class of non-electrophilic TRPA1 agonists by a structure-based virtual screening approach.

Recent work has gradually been clarifying the binding site of non-electrophilic agonists on the transient receptor potential A1 (TRPA1). This study searched for non-electrophilic TRPA1 agonists by means of in silico drug discovery techniques based on three-dimensional (3-D) protein structure. First, agonist-bound pocket structures were explored using an advanced molecular dynamics simulation starting from the cryo-electron microscopic structure of TRPA1, and several pocket structures suitable for virtual screening were extracted by structure evaluation using known non-electrophilic TRPA1 agonists. Next, 49 compounds were selected as new non-electrophilic agonist candidates from a library of natural products comprising 10,555 compounds by molecular docking toward these pocket structures. Measurement of the TRPA1 agonist activity of these compounds showed notable TRPA1 activation with three compounds (decanol, 2-ethyl-1-hexanol, phenethyl butanoate). Decanol and 2-ethyl-1-hexanol, which are categorized as fatty alcohols, in particular have a novel chemical scaffold for TRPA1 activation. The results of this study are expected to be of considerable use in understanding the molecular mechanism of TRPA1 recognition by non-electrophilic agonists.

A chemically unmodified agonistic DNA with growth factor functionality for in vivo therapeutic application.

Although growth factors have great therapeutic potential because of their regenerative functions, they often have intrinsic drawbacks, such as low thermal stability and high production cost. Oligonucleotides have recently emerged as promising chemical entities for designing synthetic alternatives to growth factors. However, their applications in vivo have been recognized as a challenge because of their susceptibility to nucleases and limited distribution to a target tissue. Here, we present the first example of oligonucleotide-based growth factor mimetics that exerts therapeutic effects at a target tissue after systemic injection. The aptamer was designed to dimerize a growth factor receptor for its activation and mitigated the progression of Fas-induced fulminant hepatitis in a mouse model. This unprecedented functionality of the aptamer can be reasonably explained by its high nuclease stability and migration to the liver parenchyma. These mechanistic analyses provided insights for the successful application of aptamer-based receptor agonists.

Oligonucleotide-Based Mimetics of Hepatocyte Growth Factor.

Oligonucleotide-based hepatocyte growth factor (HGF) mimetics are described. A DNA aptamer to Met, a cognate receptor for HGF, was shown to induce Met activation when used in dimer form. The most potent aptamer dimer, ss-0, which was composed solely of 100-mer single-stranded DNA, exhibited nanomolar potency. Aptamer ss-0 reproduced HGF-induced cellular behaviors, including migration and proliferation. The present work sheds light on oligonucleotides as a novel chemical entity for the design of growth factor mimetics.