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FGF21 upregulation by hepatitis C virus via the eIF2α-ATF4 pathway : Implications for interferon signaling suppression and TRIM31-mediated TSC degradation
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科thesi
Evaluation of brain activation related to resting pain using functional magnetic resonance imaging in cynomolgus macaques undergoing knee surgery
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科thesi
A case of refeeding triggered by severe hyperemesis gravidarum
Get PDFRefeeding syndrome (以下RFS) とは、長期の飢餓状態・低栄養状態に急激な栄養補充を行い、体液量と電解質の変化に関連した重篤な機能障害を引き起こす病態である。重症妊娠悪阻を契機に発症したRFSの一例を経験したので報告する。
症例は26歳女性、2妊0産。前医で悪阻に対し補液を行ったが、16週時に肩関節や股関節の疼痛、全身倦怠感を認め、増悪したため当院へ母体搬送となった。妊娠悪阻に加え、低カリウム血症、低リン血症、QT延長を認め、その後横紋筋融解症を発症しRFSと診断した。電解質補正、摂取エネルギー管理で、徐々に全身状態は改善し、その後の妊婦健診では異常なく経過し、妊娠39週3日に経腟分娩となった。
妊娠悪阻などによる低栄養は、RFSが発症する可能性があることや、低カリウム血症、低リン血症により、致死的な合併症をきたす恐れがあるため、栄養管理には十分な注意が必要である。Refeeding syndrome (RFS) is a condition in which prolonged starvation and undernutrition are followed by rapid nutritional replacement, causing severe functional impairment related to changes in fluid volume and electrolytes. We report a case of RFS that developed as a result of severe hyperemesis gravidarum.
The patient was a 26-year-old two gravida nulliparous woman. She had been treated for hyperemesis gravidarum by her previous physician, but at 16 weeks, she developed worsening symptoms of shoulder and hip joint pain and general malaise, then she was transferred to our hospital. In addition to hyperemesis gravidarum, hypokalemia, hypophosphatemia and QT prolongation were observed at admission and rhabdomyolysis was subsequently developed, therefore, she was diagnosed as RFS. With electrolyte replacement and energy management, her general condition gradually improved. Antenatal checkups were uneventful, and she was delivered vaginally at 39 weeks 3 days.
Hyperemesis gravidarum could lead to severe malnutrition. Once RFS is developed, fatal complications might be happened for both mother and fetus. Careful management of nutrition during pregnancy is recommended.journal articl
Development and validation of a new asthma questionnaire to help achieve a high level of control in school-age children and adolescents
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科Background: Maintaining good asthma control minimizes the risk of exacerbations and lung function decline and is a primary goal of asthma management. The Japanese Pediatric Asthma Guidelines (JPGL) employs different classification criteria for control status from other guidelines, stressing a higher level of control. Based on JPGL, we previously developed a caregiver-completed questionnaire for assessing and achieving best asthma control in preschoolers. In this study, we aimed to develop a questionnaire for school-age children and adolescents.
Methods: A working questionnaire comprising 14 items for patients and 34 items for caregivers was administered to 362 asthma patients aged 6ー15 years and their caregivers. Separately, physicians filled out a questionnaire to determine JPGL-defined control. Logistic regression analysis was performed to construct a model to predict control levels using data from a randomly selected set of completed questionnaires from two-thirds of the subjects. Validation was performed using the remaining questionnaires.
Results: A set of 7 questions, encompassing self-assessed control status at the time of the visit and in the past month, and nocturnal/early morning asthma symptoms for patients and frequency of asthma symptoms, dyspnea, rescue beta-agonist use, and asthma hospitalization for caregivers, were selected and the 7-item model showed a good statistical fit with AIC of 110.5. The model has been named the Best Asthma Control Test for School Children and Adolescents (Best ACT-S). Best ACT-S scores differed significantly in the hypothetical direction among the groups of different JPGL-defined control levels, step-up/down treatment decisions, and presence/non-presence of exacerbations in the previous year.
Conclusions: The Best ACT-S is a valid questionnaire for children/adolescents aiming for best asthma control.doctoral thesi
FGF21 upregulation by hepatitis C virus via the eIF2α-ATF4 pathway: implications for interferon signaling suppression and TRIM31-mediated TSC degradation
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）Hepatitis C virus (HCV) infection is a major cause of chronic liver diseases and is known to induce endoplasmic reticulum (ER) stress, which alters cellular homeostasis and metabolic processes. While ER stress is implicated in HCV-related diseases, its precise role remains unclear. This study identifies fibroblast growth factor 21 (FGF21) as a key host factor significantly upregulated by HCV infection. Mechanistic analyses reveal that the activation of the FGF21 promoter by HCV is primarily mediated by the transcription factor ATF4, which is upregulated through the phosphorylation of eIF2αinduced by ER stress. Additionally, CREBH activation further enhances ATF4 expression, contributing to increased FGF21 levels. TRIB3, upregulated by ATF4, acts as a negative regulator of FGF21 expression. The study also identifies FGF21-dependent upregulation of SOCS2 and TRIM31 in HCV-infected cells. SOCS2 contributes to the suppression of type 1 interferon signaling, aiding viral persistence, while TRIM31 promotes the degradation of the tumor suppressor protein TSC, activating the mTORC1 pathway and potentially promoting liver cell proliferation. These findings suggest that FGF21 upregulation in HCV-infected cells may play a role in both immune response regulation and cell proliferation, contributing to sustained viral infection and disease progression
Evaluation of brain activation related to resting pain using functional magnetic resonance imaging in cynomolgus macaques undergoing knee surgery
Get PDF浜松医科大学Hamamatsu University School of Medicin博士（医学）Purpose: Functional magnetic resonance imaging (fMRI) visualizes hemodynamic responses associated with brain and spinal cord activation. Various types of pain have been objectively assessed using fMRI as considerable brain activations. This study aimed to develop a pain model in cynomolgus macaques undergoing knee surgery and confirm brain activation due to resting pain after knee surgery.
Methods: An osteochondral graft surgery on the femoral condyle in the unilateral knee was performed on four cynomolgus macaques (Macaca fascicularis). Resting pain was evaluated as changes in brain fMRI findings with a 3.0-T MRI scanner preoperatively, postoperatively, and after postoperative administration of morphine. In the fMRI analysis, Z-values >1.96 were considered statistically significant.
Results: Brain activation without stimulation after surgery in the cingulate cortex (3.09) and insular cortex (3.06) on the opposite side of the surgery was significantly greater than that before surgery (1.05 and 1.03, respectively) according to fMRI. After the administration of morphine, activation due to resting pain decreased in the cingulate cortex (1.38) and insular cortex (1.21).
Conclusion: Osteochondral graft surgery on the femoral condyle can lead to postoperative resting pain. fMRI can reveal activation in pain-related brain areas and evaluate resting pain due to knee surgery
UBL3 overexpression enhances EV-mediated Achilles protein secretion in conditioned media of MDA-MB-231 cells
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科thesi
DESI-IMS coupled with triple quadrupole mass spectrometry demonstrated the capability of NMN imaging in Shelfordella lateralis tissue
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科Imaging mass spectrometry (IMS) has become an indispensable analytical tool for visualizing molecular distributions in biological tissues. However, the detection of many important biomolecules, such as nicotinamide mononucleotide (NMN) in tissue by IMS is still challenging due to their lower abundance. Although the sensitivity of widely used IMS instruments, desorption electrospray ionization (DESI) utilizing a time-of-flight (TOF) mass analyzer, is not sufficient to detect NMN in tissues, the recently developed DESI coupled with a triple-quadrupole (TQ) provides about ten times higher sensitivity than the DESI-Q-TOF. In this study, we first screened six insect species for NMN content using ultra-performance liquid-chromatography–tandem mass spectrometry (UPLC-MS/MS). Interestingly, Shelfordella lateralis showed significantly higher NMN content (15.5mg/100g of dry weight) than five other insect species used in this study. After screening, we tried to observe the distribution of NMN in S. lateralis using both DESI-Q-TOF and DESI-TQ, and only the DESI-TQ successfully detected the NMN in S. lateralis. DESI-TQ revealed prominent distributions of NMN in the abdomen of S. lateralis in selective reaction monitoring mode. To the best of our knowledge, this is the first report of NMN imaging in animal tissue applying IMS. Our study will contribute to the extended application of IMS for NMN imaging in mammalian tissues in the future. Furthermore, NMN imaging may help researchers to study nicotinamide adenine dinucleotide (NAD+) metabolism in living organisms, which has significant implications for medical research and diagnosis.doctoral thesi