Publications by authors named "Naoki Fujitsuka"

Article Synopsis
  • Aquaporin 2 (AQP2) is essential for water reabsorption and urine concentration, and its localization in kidney cells is influenced by anti-diuretic hormones, making it a target for specific medications.
  • This study looked at how Goreisan (GRS), a traditional Japanese herbal medicine, affects urine production and AQP2 levels in mice, particularly under conditions induced by desmopressin.
  • Findings revealed that GRS enhances diuretic effects by temporarily raising calcium levels in cells and decreasing the accumulation of phosphorylated AQP2 at the kidney's luminal surface, thus helping to regulate urine volume.
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Background: Rikkunshito (RKT), a traditional Japanese medicine, can relieve epigastric discomfort and anorexia in patients with functional dyspepsia. RKT enhances the orexigenic hormone, ghrelin. Ghrelin regulates food motivation by stimulating the appetite control center in the hypothalamus and the brain mesolimbic dopaminergic pathway (MDPW).

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  • The study investigates the effects of Hochuekkito (TJ-41), a Japanese herbal medicine, on inflammation and nutritional status in cancer patients, particularly focusing on malnutrition and muscle loss (sarcopenia).
  • Researchers analyzed 99 patients over 3 months, observing a significant reduction in the inflammatory marker C-reactive protein (CRP) in those with gastrointestinal cancer, especially in patients with metastatic disease.
  • The findings suggest that TJ-41 could be beneficial as a complementary treatment for gastrointestinal cancer by potentially reducing inflammation and helping manage muscle loss.
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Secondary lymphedema occurs after cancer surgery involving lymph node dissection owing to the lymphatic system dysfunction. However, the pathophysiology of lymphedema and the molecular pathways involved remain unknown. This study aimed to develop a rat hindlimb lymphedema model and investigate the mechanisms that drive pathophysiology and the effects of the traditional Japanese medicine goreisan on lymphedema.

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Background: Polycystic ovary syndrome (PCOS) is a common disorder resulting in irregular menstruation and infertility due to improper follicular development and ovulation. PCOS pathogenesis is mediated by downregulated follicle-stimulating hormone receptor (FSHR) expression in granulosa cells (GCs); however, the underlying mechanism remains elusive. Unkeito (UKT) is a traditional Japanese medicine used to treat irregular menstruation in patients with PCOS.

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Chemotherapy-induced sarcopenia is an unfavorable prognostic factor implicated in the development of postoperative complications and reduces the quality of life of patients with cancer. Skeletal muscle loss due to cisplatin use is caused by mitochondrial dysfunction and activation of muscle-specific ubiquitin ligases Atrogin-1 and muscle RING finger 1 (MuRF1). Although animal studies suggest the involvement of p53 in age-, immobility-, and denervation-related muscle atrophy, the association between cisplatin-induced atrophy and p53 remains unknown.

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Background: Heineke-Mikulicz (HM) strictureplasty is commonly used to treat short stenoses in Crohn's disease. However, the degree to which intestinal motility is maintained remains unclear. We compared the peristalsis and transport capacity of the sutured intestines with HM configuration and transverse (TS) and longitudinal (LS) incisions.

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Background: Daikenchuto (DKT) has positive therapeutic effects on improving various gastrointestinal disorders. The present study investigated whether or not DKT has a potential therapeutic effect on chemotherapy-induced acute small intestinal mucositis (CIM) in a rat model.

Methods: Intraperitoneal injection of 10 mg/kg methotrexate (MTX) every 3 days for a total of 3 doses was used for induction of CIM in a rat model.

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Dysregulation of lipid metabolism and diabetes are risk factors for nonalcoholic fatty liver disease (NAFLD), and the gut-liver axis and intestinal microbiome are known to be highly associated with the pathogenesis of this disease. In Japan, the traditional medicine daisaikoto (DST) is prescribed for individuals affected by hepatic dysfunction. Herein, we evaluated the therapeutic potential of DST for treating NAFLD through modification of the liver and stool metabolome and microbiome by using STAM mice as a model of NAFLD.

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Changes in the intestinal microbiota are known to occur in constipated patients. Dietary fiber restriction presents obstacles to appropriate defecation and affects fecal properties, but the relationship between fecal microbiota and fecal morphological properties remains obscure. Therefore, we examined the influence of fiber diets on the fecal microbiome and properties in rats, and the effectiveness of the Japanese traditional medicine Junchoto (JCT) in rats with fiber deficit-induced constipation.

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Melanocortin 4 receptor gene-knockout (MC4R-KO) mice are known to develop obesity with a high-fat diet. Meanwhile, daisaikoto, one of Kampo medicines, is a drug that is expected to have therapeutic effects on obesity. Here, we report the efficacy of daisaikoto in MC4R-KO mice.

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Article Synopsis
  • * Saireito, a traditional Japanese herbal medicine, was tested on mice with antibiotic-induced dysbiosis to determine its effects on leaky gut and intestinal barrier integrity over a 28-day period.
  • * Results showed that Saireito significantly reduced symptoms like fecal occult bleeding and cecum enlargement, while enhancing intestinal barrier function and improving gut microbiota diversity, suggesting its potential as a treatment for conditions like ulcerative colitis.
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We performed RNA-seq analyses of mRNA isolated from five organs, liver, bone, heart, kidney and blood at the pre-symptomatic state of klotho mice with/without administration of a Japanese traditional herbal medicine, juzentaihoto (JTT). Data of differentially expressed genes (DEG) with/without JTT was included. Intron retention (IR) is an important regulatory mechanism that affects gene expression and protein functions.

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Muscle atrophy is commonly observed during cisplatin chemotherapy, leading to a reduced QOL in cancer patients. Reduced skeletal muscle mass caused by cisplatin treatment results from the activation of ubiquitin ligases-Atrogin-1 and MuRF1, but the precise mechanisms are poorly understood. In this study, we investigated the possible involvement of mitochondrial dysfunction, including reactive oxygen species (ROS) generation and ATP production, in cisplatin-induced muscle atrophy.

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Malnutrition impairs basic daily activities and leads to physical frailty, which is aggravated in the elderly compared with young adults. It is also well-known that the elderly are more vulnerable to metabolic stress. Therefore, in this study, using a food restricted (FR) mouse, we aimed to evaluate the effect of aging on locomotor activity and liver metabolic function.

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Background: Liver cirrhosis is an end-stage multiple liver disease. Mesenchymal stem cells (MSCs) are an attractive cell source for reducing liver damage and regressing fibrosis; additional therapies accompanying MSCs can potentially enhance their therapeutic effects. Kampo medicines exhibit anti-inflammatory and anti-oxidative effects.

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EGFR tyrosine kinase inhibitors (TKIs) are mainly used to treat non-small cell lung cancer; however, adverse effects such as severe diarrhea represent a major obstacle towards the continuation of EGFR-TKIs therapy. Chloride channels, which control the fluid flow in the intestinal lumen, are proposed as an important target to remediate EGFR-TKIs-induced diarrhea, but the mechanism remains unclear. The aim of this study was to clarify the mechanism underlying EGFR-TKIs-induced diarrhea with a particular focus on the role of intestinal chloride channels.

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Article Synopsis
  • * In aged mice, severe food restriction resulted in fatal hypoglycemia and lower autophagy compared to younger mice, with certain changes in liver expressions indicating impaired energy balance.
  • * Treatments that enhance autophagy, like the herbal formula hochuekkito, may help restore essential metabolic functions and offer potential therapeutic benefits for frail older adults suffering from undernutrition.
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Article Synopsis
  • Intron retention (IR) plays a key role in regulating gene expression and protein function, with findings from klotho mice showing that retained introns accumulate in organs like the liver.
  • A traditional Japanese herbal medicine was found to recover a subset of these retained introns in the liver, marking the first documented instance of IR recovery through medicinal treatment.
  • Metabolome analysis indicated that klotho mice were experiencing starvation stress, and the herbal treatment improved liver metabolism at the transcriptional level, suggesting that IR accumulation can serve as a potential marker for early aging signs.
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  • Weak acids with pH values between 4-7 are linked to gastroesophageal reflux disease (GERD) symptoms, particularly heartburn, by increasing production of prostaglandin E (PGE).
  • This study found that weak acids elevate PGE levels in both normal and cancerous esophageal cells, with the most significant production occurring at pH 4-5.
  • The research suggests that targeting pH levels in the treatment of GERD could help alleviate symptoms, as interventions that inhibit certain pathways related to PGE production showed effectiveness.
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  • A study investigated the effects of a traditional Japanese medicine called bukuryoingohangekobokuto (BGH) on delayed gastric emptying in stress model mice.
  • * The stress hormone corticotropin-releasing factor (CRF) was shown to significantly delay gastric emptying in these mice, but BGH treatment helped improve this delay.
  • * BGH appears to work by targeting specific receptors and enzymes, suggesting it could be beneficial for individuals with gastrointestinal issues linked to anxiety and depression.
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Background: The traditional Japanese herbal medicine, daikenchuto (DKT), has been used to treat constipation and postoperative ileus. However, the precise mechanisms involved in the pharmacological effects of DKT remain uncertain. The aim of this study was to clarify the effect of DKT on motor patterns and transit activity in the isolated rat colon.

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Taste stimulants play important roles in triggering digestion and absorption of nutrients and in toxin detection, under the control of the gut-brain axis. Bitter compounds regulate gut hormone secretion and gastrointestinal motility through bitter taste receptors (TAS2Rs) located in the taste buds on the tongue and in the enteroendocrine cells. Gastric accommodation (GA) is an important physiologic function.

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Article Synopsis
  • Prostaglandin E2 plays a role in tumor development and induces M2 macrophages, which contribute to an immunosuppressed environment favoring tumors.
  • The study evaluated the effects of the traditional Japanese medicine Hangeshashinto (TJ-14) on preventing esophageal cancer in a rat model, finding that it reduced the incidence of cancer and Barrett's metaplasia compared to a control diet.
  • Results showed that 67% of control rats developed esophageal cancer, while only 10% of rats receiving TJ-14 did, along with a significant reduction in M2 macrophages in the TJ-14 group, indicating its potential protective effects against cancer progression.
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Background & Aim: Changes in eating behavior occur in the elderly due to oral and swallowing dysfunctions. We aimed to clarify the difference between basal meal patterns of young and aged mice in relation to appetite regulating hormones.

Methods: Thirty two of young (7-week-old) and aged (23-25-month-old) C57BL/6 male mice were acclimated to a single housing and then transferred to a highly sensitive automated feeding monitoring device.

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