Effects of Cimetidine and Dolutegravir on the Endogenous Drug-Drug Interaction Biomarkers for Organic Cation Transporter 2 and Multidrug and Toxin Extrusion Protein 1 in Healthy Volunteers.

This study was designed to assess the quantitative performance of endogenous drug-drug interaction (DDI) biomarkers (N1-methylnicotinamide (1-NMN), N1-methyladenosine (mA), and creatinine) for the organic cation transporters, OCT2 and MATE1/2K in the kidney. Ten healthy volunteers received cimetidine (400 and 800 mg, single dose) or dolutegravir (50 mg, twice a day) together with metformin (500 mg). Cimetidine and dolutegravir were considered to act mainly as MATE1/2K and OCT2 inhibitors, respectively.

Effects of Aerobic Exercise and Resistance Training on Cognitive Function: Comparative Study Based on FNDC5/Irisin/BDNF Pathway.

Introduction: Exercise has been recommended to suppress or prevent cognitive decline. Aerobic exercise (AE) may suppress cognitive decline via the fibronectin type III domain-containing protein 5 (FNDC5)/irisin/brain-derived neurotrophic factor (BDNF) pathway, and resistance training (RT) has a preventive effect on cognitive decline. However, the underlying mechanism remains unclear.

FNDC5/irisin mediates the protective effects of Innovative theta-shaking exercise on mouse memory.

As a passive motion and non-invasive treatment, theta-shaking exercise is considered an alternative to traditional active exercise for slowing down brain ageing. Here, we studied the influence of theta-shaking exercise on fibronectin type III domain containing 5/irisin (FNDC5/irisin) in the anterior nucleus of the thalamus, hippocampus, and medial prefrontal cortex (ATN-HPC-MPFC). Further, we assessed memory in senescence-accelerated prone mice (SAMP-10 mice) using a behavioural test to confirm the protective effect of theta-shaking exercise against age-related memory decline.

Trapping bond exchange phenomenon revealed for off-stoichiometry cross-linking of phase-separated vitrimer-like materials.

Vitrimer materials combined with nano-phase separated structures have attracted attention, expanding the tuning range of physical properties, such as flow and creep properties. We recently demonstrated a preparation of vitrimer-like materials with phase-separated nanodomains in which dissociative bond exchange -alkylation of quaternized pyridine was operated. In this study, we demonstrate a new finding about the bond exchange mechanism: that is, the trapping bond exchange phenomenon.

Exercise through Shaking Stimuli Suppresses Cancer Growth via the Wnt pathway in ApcMin/+ Mice.

Objective: Exercise has been reported to suppress colorectal cancer; however, the mechanism of suppression by exercise and its effect on the Wnt pathway, which is particularly involved in the early stage of carcinogenesis, remain unclear. In this study, we subjected ApcMin/+ mice to exercise by shaking stimuli to investigate the mechanisms of suppressing colorectal cancer, and focused on the Ca2+ pathway, which is one of the β-catenin-independent Wnt signaling pathways that suppress the accumulation of β-catenin.

Methods: Mice in the exercise group were subjected to exercise by shaking stimuli for 30 min/session, 6 sessions/ week, for a total of 11 weeks.

School-based online survey on chronic headache, migraine, and medication-overuse headache prevalence among children and adolescents in Japanese one city - Itoigawa Benizuwaigani study.

Background: We investigated the prevalence of headache, migraine, and medication-overuse headache (MOH) among children and adolescents through a school-based online questionnaire. We also investigated the triggers for migraine among them and the effect of the COVID-19 pandemic on headache frequency.

Methods: Children and adolescents aged 6-17 y.

Headache education by leaflet distribution during COVID-19 vaccination and school-based on-demand e-learning: Itoigawa Geopark Headache Awareness Campaign.

Objective: We prospectively performed the Itoigawa Headache Awareness Campaign from August 2021 to June 2022, with two main interventions, and evaluated its effectiveness.

Background: Headache is a common public health problem, but its burden could be reduced by raising awareness about headache and the appropriate use of acute and prophylactic medication. However, few studies on raising headache awareness in the general public have been reported.

Impact of Direction of Transport on the Evaluation of Substrate Recognition of Mouse Multidrug and Toxin Extrusion Protein 1.

Multidrug and toxin extrusion protein (MATE/SLC47A) secretes metabolites and xenobiotics into the urine in the proximal tubules of the kidney. Uptake assays have been commonly used for evaluating MATE-mediated transport of new chemical entities in drug development. The purpose of this study was to examine the relationship between in vitro uptake activities by MATEs and the impact of MATE-mediated transport in in vivo renal secretion.

Exercise by Shaking Alleviates the Decline in Memory due to Aging: A Study in Mice.

Introduction: Although exercise can prevent cognitive decline due to aging, few elderly individuals are able to exercise for long. Therefore, an exercise method for older adults that is feasible for a long duration without overexertion is necessary. In this study, we focused on exercise by shaking.

Novel shaking exercises for hippocampal and medial prefrontal cortex functioning maintain spatial working memory.

Introduction: The decline in spatial working memory is one of the earliest signs of normal brain aging.

Objective: We developed a novel physical exercise method, termed the "shaking exercise," to slow down this process.

Methods: The experimental protocol included administering the shaking exercise for 8-32 weeks in male senescence-accelerated mouse prone 10 (SAMP-10).

Questionnaire-Based Survey during COVID-19 Vaccination on the Prevalence of Elderly's Migraine, Chronic Daily Headache, and Medication-Overuse Headache in One Japanese City-Itoigawa Hisui Study.

Background: The prevalence of headache disorders, migraine, chronic daily headache (CDH), and medication-overuse headache (MOH) among the elderly in Japan has not been sufficiently investigated. We performed a questionnaire-based survey and revealed 3-month headache prevalence and headaches' characteristics.

Methods: The population aged over 64 was investigated in Itoigawa during their third coronavirus disease 2019 vaccination.

Body-Specific Attention to the Hands and Feet in Healthy Adults.

To execute the intended movement, the brain directs attention, called body-specific attention, to the body to obtain information useful for movement. Body-specific attention to the hands has been examined but not to the feet. We aimed to confirm the existence of body-specific attention to the hands and feet, and examine its relation to motor and sensory functions from a behavioral perspective.

Temporal motifs in patent opposition and collaboration networks.

Patents are intellectual properties that reflect innovative activities of companies and organizations. The literature is rich with the studies that analyze the citations among the patents and the collaboration relations among companies that own the patents. However, the adversarial relations between the patent owners are not as well investigated.

Questionnaire-based survey on the prevalence of medication-overuse headache in Japanese one city-Itoigawa study.

Objective: The medication-overuse headache (MOH) prevalence has not been investigated in a general Japanese population. We performed questionnaire-based survey and revealed MOH prevalence and its characteristics. We also performed clustering to obtain insight for MOH subgrouping.

Maintenance of the Amygdala-Hippocampal Circuit Function with Safe and Feasible Shaking Exercise Therapy in SAMP-10 Mice.

Introduction: Patients with dementia show reduced adaptive, behavioral, and physiological responses to environmental threats. Physical exercise is expected to delay brain aging, maintain cognitive function and, consequently, help dementia patients face threats and protect themselves skillfully.

Methods: To confirm this, we aimed to investigate the effects of the shaking exercise on the avoidance function in the senescence-accelerated mouse-prone strain-10 (SAMP-10) model at the behavioral and tissue levels.

Novel TLR2xTLR4 Bispecific Antibody Inhibits Bacterial Sepsis.

Toll-like receptors (TLRs) sense microbial infection through recognition of pathogen-associated molecular patterns. For example, TLR4 responds to the lipopolysaccharide of gram-negative bacteria, whereas TLR2 recognizes a broad range of microbial ligands. Both receptors are, therefore, compelling targets for treating sepsis.

Maintaining Aging Hippocampal Function with Safe and Feasible Shaking Exercise in SAMP10 Mice.

Introduction: The disabling effects of dementia, an incurable disease with little effect on mortality, affect society far more than many other conditions.

Objective: The aim of this study was to stop or delay the onset of dementia using low-cost methods such as physical exercise.

Methods: Senescence-accelerated model-prone (SAMP) 10 mice were made to perform a user-friendly shaking exercise for 25 weeks.

A novel device to prevent osteoporosis by promoting bone metabolism using a newly developed double-loading stimulation with vibration and shaking.

In Japan, 13 million people have osteoporosis, including approximately 9 hundred thousand people who are bedridden owing to bone fractures from falls. Preventing osteoporosis is considered to be an important and effective way of preventing fall-related fractures. Thus, we developed a novel method of locomotor stimulation and analyzed its effectiveness in mice.

Effect of shaking and vibration stimulation on lumbar vertebrae in ovariectomized mice.

Objectives: Bone fractures affect the activities of daily living and lower quality of life, so investigating preventative measures is important. We developed novel stimulation equipment that combined a vibration stimulus with a shaking stimulus for preventing osteoporosis (one of the causes of bone fractures). We aimed to investigate the effect of this equipment on ovariectomized mice.

Investigation of non-linear Mate1-mediated efflux of trimethoprim in the mouse kidney as the mechanism underlying drug-drug interactions between trimethoprim and organic cations in the kidney.

The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with K values (μM) of 0.030-0.

Different Involvement of OAT in Renal Disposition of Oral Anticoagulants Rivaroxaban, Dabigatran, and Apixaban.

This study aimed to investigate the interactions of 3 anticoagulants, rivaroxaban, apixaban, and dabigatran, with 5 human solute carrier transporters, hOAT1, hOAT3, hOCT2, hOATP1B1, and hOATP1B3. Apixaban inhibited hOAT3, hOATP1B1, and hOATP1B3, and rivaroxaban inhibited hOAT3 and hOATP1B3, with IC values of >20 and >5 μM, respectively. The effect of dabigatran was negligible or very weak, so significant drug interactions at therapeutic doses are unlikely.

Effectiveness of exercise-induced cytokines in alleviating arthritis symptoms in arthritis model mice.

Recently, health awareness in Japan has been increasing and active exercise is now recommended to prevent lifestyle-related diseases. Cytokine activities have many positive effects in maintaining the health of a number of organs in the body. Myokines are cytokines secreted by skeletal muscles in response to exercise stimulation, and have recently generated much attention.

Angioblast Derived from ES Cells Construct Blood Vessels and Ameliorate Diabetic Polyneuropathy in Mice.

Background: Although numerous reports addressing pathological involvements of diabetic polyneuropathy have been conducted, a universally effective treatment of diabetic polyneuropathy has not yet been established. Recently, regenerative medicine studies in diabetic polyneuropathy using somatic stem/progenitor cell have been reported. However, the effectiveness of these cell transplantations was restricted because of their functional and numerical impairment in diabetic objects.

Organic cation transporter/solute carrier family 22a is involved in drug transfer into milk in mice.

Drug transfer into milk is a general concern during lactation. So far, breast cancer resistance protein (Bcrp) is the only transporter known to be involved in this process, whereas participation of other transporters remains unclear. We investigated the importance of organic cation transporter (Oct) in drug transfer into milk in mice.

Evaluation of the potency of telaprevir and its metabolites as inhibitors of renal organic cation transporters, a potential mechanism for the elevation of serum creatinine.

Telaprevir-based triple therapy is a highly effective treatment for chronic hepatitis C. However, adverse reactions include reversible and dose-dependent elevation of serum creatinine levels. We speculated that this effect reflects inhibition of the renal organic cation transporters hOCT2, hMATE1, and hMATE2-K by telaprevir or its metabolites (VRT-127394 and VRT-0922061).