BACKGROUND: Mitochondria, which harbor their own genome (mtDNA), have attracted attention due to the potential of mtDNA copy number (mtDNA-CN) as an indicator of mitochondrial dysfunction. Although mtDNA-CN has been proposed as a simple and accessible biomarker for metabolic disorders such as metabolic dysfunction-associated steatotic liver disease, the underlying mechanisms and the causal relationship remain insufficiently elucidated. In this investigation, we combined longitudinal epidemiological data, animal studies, and in vitro assays to elucidate the potential causal relationship between reduced mtDNA-CN and the development of steatotic liver disease (SLD). METHODS: We conducted a longitudinal study using data from a health examination cohort initiated in 1981 in Yakumo, Hokkaido, Japan. Data from examinations performed in 2015 and 2022 were analyzed, focusing on 76 subjects without SLD at baseline (2015) to assess the association between baseline mtDNA-CN and subsequent risk of SLD development. In addition, 28-day-old SD rats were fed ad libitum on a 45% high-fat diet and dissected at 2 and 8 weeks of age. Blood and liver mtDNA-CN were measured and compared at each feeding period. Additionally, in vitro experiments were performed using HepG2 cells treated with mitochondrial function inhibitors to induce mtDNA-CN depletion and to examine its impact on intracellular lipid accumulation. RESULTS: Epidemiological analysis showed that the subjects with low mtDNA-CN had a significantly higher odds ratio for developing SLD compared to high (odds ratio [95% confidence interval]: 4.93 [1.08-22.50]). Analysis of the animal model showed that 8 weeks of high-fat diet led to the development of fatty liver and a significant decrease in mtDNA-CN. A further 2 weeks of high-fat diet consumption resulted in a significant decrease in hepatic mtDNA-CN, despite the absence of fatty liver development, and a similar trend was observed for blood. Complementary in vitro experiments revealed that pharmacologically induced mitochondrial dysfunction led to a significant reduction in mtDNA-CN and was associated with increases in intracellular lipid accumulation in HepG2 cells. CONCLUSIONS Our findings suggest that reduced mtDNA-CN may contribute causally to SLD development and could serve as a convenient, noninvasive biomarker for early detection and risk assessment.
Animals ; DNA, Mitochondrial/genetics* ; Humans ; Male ; DNA Copy Number Variations ; Female ; Fatty Liver/blood* ; Rats ; Middle Aged ; Longitudinal Studies ; Rats, Sprague-Dawley ; Adult ; Japan/epidemiology* ; Aged ; Biomarkers/blood* ; Hep G2 Cells ; Diet, High-Fat/adverse effects*

Objective: Previously, we reported that insulinoma-associated protein 1 (INSM1) immunohistochemistry (IHC) showed high sensitivity for neuroendocrine carcinoma of the uterine cervix and was an effective method for histopathological diagnosis, but that its specificity remained to be verified. Therefore, the aim was to verify the specificity of INSM1 IHC for a large number of non-neuroendocrine neoplasia (NEN) of the cervix. Methods: RNA sequences were performed for cell lines of small cell carcinoma (TCYIK), squamous cell carcinoma (SiHa), and adenocarcinoma (HeLa). A total of 104 cases of formalin-fixed and paraffin-embedded specimens, 16 cases of cervical NEN and 88 cases of cervical non-NEN, were evaluated immunohistochemically for conventional neuroendocrine markers and INSM1. All processes without antigen retrieval were performed by an automated IHC system. Results: The transcripts per million levels of INSM1 in RNA sequences were 1505 in TCYIK, 0 in SiHa, and HeLa. INSM1 immunoreactivity was shown only in the TCYIK. Immunohistochemical results showed that 15 cases of cervical NEN showed positive for INSM1; the positivity score of the tumor cell population and the stain strength for INSM1 were high. Two of the 88 cases of cervical non-NENs were positive for INSM1 in one case each of typical adenocarcinoma and squamous cell carcinoma. The sensitivity of INSM1 for cervical NEN was 94%; specificity, 98%; the positive predictive value, 88%; and the negative predictive value, 99%. Conclusion INSM1 is an adjunctive diagnostic method with excellent specificity and sensitivity for diagnosing cervical NEN. Higher specificity can be obtained if morphological evaluation is also performed.

We here report three cases of choroidal metastases with ocular pain and visual symptoms treated with palliative irradiation. Case 1: A 71-year-old woman was treated with chemotherapy for multiple metastases after surgery for right breast cancer. Sixteen years after surgery, a right choroidal metastasis with ocular pain and visual disturbance was detected. Palliative irradiation to this lesion achieved reduction in ocular pain and shrank the tumor. Case 2: A 54-year-old man presented with right ocular pain and abnormal vision and was diagnosed as having right lung cancer with multiple systemic metastases. Palliative irradiation to a right choroidal metastasis achieved reduction in ocular pain and shrank the tumor. Case 3: A 71-year-old woman developed left eye pain 17 months after surgery for lung cancer in the right upper lobe. She was diagnosed as having a left choroidal metastasis. After palliative irradiation, the tumor shrank and the left eye pain temporarily resolved. Palliative radiation therapy for choroidal metastasis with ocular pain and visual symptoms seems to be effective in improving symptoms.

Online databases are crucial infrastructures to facilitate the wide effective and efficient use of mouse mutant resources in life sciences. The number and types of mouse resources have been rapidly growing due to the development of genetic modification technology with associated information of genomic sequence and phenotypes. Therefore, data integration technologies to improve the findability, accessibility, interoperability, and reusability of mouse strain data becomes essential for mouse strain repositories. In 2020, the RIKEN BioResource Research Center released an integrated database of bioresources including, experimental mouse strains, Arabidopsis thaliana as a laboratory plant, cell lines, microorganisms, and genetic materials using Resource Description Framework-related technologies. The integrated database shows multiple advanced features for the dissemination of bioresource information. The current version of our online catalog of mouse strains which functions as a part of the integrated database of bioresources is available from search bars on the page of the Center (https://brc.riken.jp) and the Experimental Animal Division (https://mus.brc.riken.jp/) websites. The BioResource Research Center also released a genomic variation database of mouse strains established in Japan and Western Europe, MoG+ (https://molossinus.brc.riken.jp/mogplus/), and a database for phenotype-phenotype associations across the mouse phenome using data from the International Mouse Phenotyping Platform. In this review, we describe features of current version of databases related to mouse strain resources in RIKEN BioResource Research Center and discuss future views.

Online databases are crucial infrastructures to facilitate the wide effective and efficient use of mouse mutant resources in life sciences. The number and types of mouse resources have been rapidly growing due to the development of genetic modification technology with associated information of genomic sequence and phenotypes. Therefore, data integration technologies to improve the findability, accessibility, interoperability, and reusability of mouse strain data becomes essential for mouse strain repositories. In 2020, the RIKEN BioResource Research Center released an integrated database of bioresources including, experimental mouse strains, Arabidopsis thaliana as a laboratory plant, cell lines, microorganisms, and genetic materials using Resource Description Framework-related technologies. The integrated database shows multiple advanced features for the dissemination of bioresource information. The current version of our online catalog of mouse strains which functions as a part of the integrated database of bioresources is available from search bars on the page of the Center (https://brc.riken.jp) and the Experimental Animal Division (https://mus.brc.riken.jp/) websites. The BioResource Research Center also released a genomic variation database of mouse strains established in Japan and Western Europe, MoG+ (https://molossinus.brc.riken.jp/mogplus/), and a database for phenotype-phenotype associations across the mouse phenome using data from the International Mouse Phenotyping Platform. In this review, we describe features of current version of databases related to mouse strain resources in RIKEN BioResource Research Center and discuss future views.

Port site recurrence is a rare but well-documented adverse event peculiar to laparoscopic surgery. We report an unusual outcome of unexpected early stage ovarian cancer in which port site recurrence occurred after laparoscopic surgery and was followed by diffuse subcutaneous metastases. A 31-year-old Japanese woman with a large tumor in her abdomen visited our hospital. Because no intratumoral solid component was detected on diagnostic imaging, the tumor was diagnosed as a benign ovarian tumor and the patient underwent left ovarian laparoscopic cystectomy. Contrary to our expectations, however, the ovarian tumor was a mucinous carcinoma. We performed additional surgery, but the tumor recurred in the umbilical area, and multiple subcutaneous metastases later appeared. The curative effect of chemotherapy and radiation was limited. This atypical metastatic distribution of an extremely small amount of cancer might have been caused by the laparoscopic procedure. Protection against tumor cell dissemination is necessary during all forms of laparoscopic surgery.

BACKGROUND/AIMS: Evidence that general anesthesia (GA) reduces the operative time of esophageal endoscopic submucosal dissection (ESD) is currently insufficient. This study aims to evaluate the efficacy and safety of esophageal ESD under GA. METHODS: A total of 227 lesions from 198 consecutive patients with superficial esophageal neoplasms treated by ESD at 3 Japanese institutions between April 2011 and September 2017 were included in this retrospective study. For ESD, GA and deep sedation (DS) were used in 102 (51.5%, GA group) and 96 patients (48.5%, DS group), respectively. RESULTS: There were no statistically significant differences in age, sex, or comorbidities between the groups. In the GA group, the tumor size was larger (21 [3–77] mm vs. 14 [3–63] mm, p<0.001), luminal circumference was larger (≥2/3; 13.9% vs. 5.4%, p=0.042), procedure time was shorter (28 [5–202] min vs. 40 [8–249] min, p<0.001), and submucosal dissection speed was faster (25.2 [7.8–157.2] mm² /min vs. 16.2 [2.4–41.3] mm² /min, p<0.001). The rates of intraoperative perforation and aspiration pneumonia were lower in the GA group, but the difference did not achieve statistical significance (p=0.242 and p=0.242). CONCLUSIONS: GA shortens the procedure time of esophageal ESD.
Anesthesia ; Anesthesia, General ; Asian Continental Ancestry Group ; Comorbidity ; Deep Sedation ; Esophageal Neoplasms ; Humans ; Operative Time ; Phenobarbital ; Pneumonia, Aspiration ; Retrospective Studies

The number of surgical treatments for acute aortic dissection in octogenarians is increasing. They should return to their daily life as soon as possible after the operation without any complications. Some literature reported that minimally invasive cardiac surgery (MICS) helps quick recovery for the patients. We report a case of minimally invasive ascending aorta replacement for Stanford type A chronic thrombosed aortic dissection in an octogenarian to help quick recovery. An 81-year-old man was admitted in our hospital suffering from chest and back pain. Enhanced CT scan showed Stanford type A acute thrombosed aortic dissection. The diameter of ascending aorta was 45 mm and the diameter of false lumen was 7 mm. Therefore we decided on medical treatment for this patient according to the guideline. After four weeks medical treatment, ascending aorta was dilated to 49 mm and the false lumen also expanded to 9 mm. He underwent minimally invasive ascending aorta replacement to help quick recovery considering his age. He was discharged 11 days postoperatively without any complications. MICS offers a better cosmetic result, less blood loss, less pain, better respiratory function and quick recovery. Thus, minimally invasive operation for the elderly is also very satisfactory.

To detect the type of contact dermatitis caused due to the handling ofAlstroemeria wilhelmina, 1% α-methylene-λ-butyrolactone (α-MBL) dissolved in physiological alien and a five-fold diluted saline solution of original extracts of flowers, leaves and stems of the flower were applied to guinea-pigs for extracts were applied to the animals as the challenge treatment in compliance with the guinea-pig maximization test (GMT). As a consequence, not only primary irritant dermatitis was observed, but also delayed type allergic contact dermatitis due toAlstroemeria wilhelmina was observed. α-MBL determined in the extracts using high-performance liquid chromatography (HPLC) was found to be the biochemical material cause of the contact dermatitis. the flower region contained α-MBL in the highest concentrations compared with those of the leaves and stems. Therefore, the quantification of α-MBL in the extracts was concluded as being a useful evaluating method for contact dermatitis due to the handling ofAlstroemeria.

To detect the type of contact dermatitis caused due to the handling of Alstroemeria wilhelmina, 1% α-methylene-γ-butyrolactone (α-MBL) dissolved in physiological saline and a five-fold diluted saline solution of original extracts of flowers, leaves and stems of the flower were applied to guinea-pigs for induction treatment, and 0.1% α-MBL physiological saline and a ten-fold diluted solution of the original extracts were applied to the animals as the challenge treatment in compliance with the guinea-pig maximization test (GMT). As a consequence, not only primary irritant dermatitis was observed, but also delayed type allergic contact dermatitis due to Alstroemeria wilhelmina was observed. α-MBL determined in the extracts using high-performance liquid chromatography (HPLC) was found to be the biochemical material cause of the contact dermatitis. The flower region contained α-MBL in the highest concentrations compared with those of the leaves and stems. Therefore, the quantification of α-MBL in the extracts was concluded as being a useful evaluating method for contact dermatitis due to the handling of Alstroemeria.
Swine ; Dermatitis, Contact ; BUTYROLACTONE ; Saline ; Pulmonary evaluation