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Enterobacterial common antigen repeat-unit flippase WzxE is required for Escherichia coli growth under acidic conditions, low temperature, and high osmotic stress conditions
Full text linkColanic acid and enterobacterial common antigen (ECA) are cell-surface polysaccharides that are produced by many Escherichia coli isolates. Colanic acid is induced under acidic, low temperature, and high-salt conditions and is important for E. coli resistance to these stresses; however, the role of ECA in these stresses is less clear. Here, we observed that knockout of flippase wzxE, which translocates lipid-linked ECA repeat units from the cytoplasmic side of the inner membrane to the periplasmic side, resulted in the sensitivity of E. coli BW25113 to acidic conditions. The wzxE-knockout mutant showed reduced growth potential and viable counts in vegetable extracts with acidic environments, including cherry tomatoes, carrots, celery, lettuce, and spinach. A double-knockout strain of wzxE and wecF (glycosyltransferase that adds the third-and-final sugar of the lipid-linked ECA repeat unit) was not sensitive to acidic conditions, with similar results obtained for a double-knockout strain of wzxE and wcaJ (glycosyltransferase that initiates colanic acid lipid-linked repeat-unit biosynthesis). The wzxE-knockout mutant was sensitive to low temperatures or high-salt conditions, which induced colanic acid synthesis, and these sensitivities were abolished by the additional knockout of wcaJ. These results suggest that lipid-linked ECA repeat units confer E. coli susceptibility to acidic, low temperatures, and high-salt conditions in a colanic acid-dependent manner and that wzxE suppresses this negative effect
ADAR1-high tumor-associated macrophages induce drug resistance and are therapeutic targets in colorectal cancer
Full text linkBackground Colorectal cancer (CRC) is considered the third most common type of cancer worldwide. Tumor-associated macrophages (TAMs) have been shown to promote drug resistance. Adenosine-to-inosine RNA-editing, as regulated by adenosine deaminase acting on RNA (ADAR), is a process that induces the posttranscriptional modification of critical oncogenes. The aim of this study is to determine whether the signals from cancer cells would induce RNA-editing in macrophages.
Methods The effects of RNA-editing on phenotypes in macrophages were analyzed using clinical samples and in vitro and in vivo models.
Results The intensity of the RNA-editing enzyme ADAR1 (Adenosine deaminase acting on RNA 1) in cancer and mononuclear cells indicated a strong positive correlation between the nucleus and cytoplasm. The ADAR1-positive mononuclear cells were positive for CD68 and CD163, a marker for M2 macrophages. Cancer cells transport pro-inflammatory cytokines or ADAR1 protein directly to macrophages via the exosomes, promoting RNA-editing in AZIN1 (Antizyme Inhibitor 1) and GLI1 (Glioma-Associated Oncogene Homolog 1) and resulting in M2 macrophage polarization. GLI1 RNA-editing in the macrophages induced by cancer cells promotes the secretion of SPP1, which is supplied to the cancer cells. This activates the NF kappa B pathway in cancer cells, promoting oxaliplatin resistance. When the JAK inhibitors were administered, oncogenic RNA-editing in the macrophages was suppressed. This altered the macrophage polarization from M2 to M1 and decreased oxaliplatin resistance in cancer cells.
Conclusions This study revealed that ADAR1-high TAMs are crucial in regulating drug resistance in CRC and that targeting ADAR1 in TAMs could be a promising treatment approach for overcoming drug resistance in CRC
Molecular Iodine-Catalyzed Synthesis of 3,3-Disubstituted Isatins: Total Synthesis of Indole Alkaloid, 3,3-Dimethoxy-2-oxindole
Full text link3,3-Dialkoxy-2-oxindoles are prevalent in natural products and exhibit unique biological activities. Among them, acyclic alkoxy analogues show instability in acidic conditions, making access to acyclic isatin ketals highly challenging. Conventional methods for the synthesis of 3,3-dialkoxy-2-oxindoles usually require strongly acidic and harsh reaction conditions, resulting in a low overall efficiency. Herein, we report on an acid- and metal-free protocol for the synthesis of 3,3-dialkoxy-2-oxindoles from isatins through an iodine-catalyzed ketalization. This photochemical protocol does not require the use of any specific reagents such as metal catalysts. Furthermore, the total synthesis of an unprecedented 2-oxindole alkaloid bearing 3,3-dimethoxy moiety is achieved
A case report of ineffective electroconvulsive therapy for chronic pain
Full text linkBackground: Somatic symptom disorder (SSD), which includes chronic pain, is a common mental disorder characterized by significant functional impairment and other psychiatric comorbidities. Electroconvulsive therapy (ECT) has been proposed as a potential treatment for refractory chronic pain. However, evidence supporting its efficacy is limited and/or low quality. We present a case of SSD with chronic pain in which ECT was ineffective.
Case Presentation: The patient was a 63-year-old man with chronic pain in the lower back, buttocks, thighs, and soles of the feet. The duration of his chronic pain was 3.8 years. He was diagnosed with Bertolotti's syndrome and SSD. He did not meet the criteria for major depressive disorder. He kept physically active by walking and doing exercises to distract himself from his pain. He strongly perceived pain as a physical issue and preferred ECT over psychotherapy. Despite undergoing 10 ECT sessions with adequate seizures, his pain persisted. After four sessions, he experienced despair over the lack of improvement in pain, which temporarily intensified his suicidal ideation. After undergoing ECT, he continued to maintain his activities, including walking and exercise, while his catastrophic thinking about pain persisted.
Conclusion: The ineffectiveness of ECT in this case highlights the need for balanced counseling, particularly for patients who consider ECT a last-resort treatment. Psychological monitoring and depression screening are essential, especially given the risk of heightened despair or suicidal ideation when ECT is ineffective. Therefore, collaborative decision-making based on accurate information is vital
Lymphatic flow dynamics under exercise load assessed with thoracic duct ultrasonography
Full text linkThe thoracic duct (TD) is the largest lymphatic vessel proximal to the venous system. It undergoes morphological changes in response to lymph flow from the periphery, with automatic contraction controlling the dynamics to propel lymph toward the venous system. Recent advancements in ultrasonography have facilitated non-invasive observations of the TD’s terminal, including its valve and wall motions. Observations of TD movements allow predictions of lymphatic flow dynamics. However, no studies have yet documented the changes in the TD under exercise-induced lymph flow enhancement in humans. Here, using 18-MHz high-frequency ultrasonography, we demonstrate for the first time that the TD diameter significantly expands under exercise load. This study analyzed 20 participants; the maximum TD diameters at rest and post-exercise were 2.69 ± 1.06 mm and 3.41 ± 1.32 mm, respectively (p = 0.00000056). While various methods exist for observing the TD, our approach—dynamically monitoring the TD diameter using sonography in real time and correlating it with lymphatic flow dynamics—offers a novel contribution
Occupational therapist‐guided exercise increased white blood cell and neutrophil counts during clozapine treatment: A case report
Full text linkBackground: Moderate exercise increases white blood cells and neutrophils. However, there are no reports on the relationship between exercise intensity and these cells. We observed a patient taking clozapine whose white blood cell and neutrophil counts were borderline. Supervised exercise therapy with an occupational therapist stabilized these counts.
Case Presentation: A 50-year-old woman with treatment-resistant schizophrenia was prescribed clozapine. By Day 63, the clozapine dosage had been increased to 450 mg/day. Additionally, she was advised to perform a 30-min walking exercise program 1 h before blood tests. Exercise therapy supervised by an occupational therapist was performed eight times, and self-training was performed five times. Exercise intensity was monitored using the Borg Scale for subjective evaluation and the Karvonen formula for objective evaluation. Supervised exercise therapy with an occupational therapist resulted in greater increases on the Borg Scale and Karvonen formula than did self-training. It also induced increases in white blood cells and neutrophils. Her psychiatric symptoms improved, and she was discharged on Day 71. A blood test taken after discharge revealed that her white blood cell and neutrophil counts were within the normal range and she continued to take clozapine for 2 years. She has since been able to enjoy a calm and relaxed life at home.
Conclusion: Exercise involving subjective and objective evaluation by an occupational therapist effectively increased white blood cells and neutrophils during clozapine treatment. Supervised exercise therapy by an occupational therapist is important when self-exercise is insufficient for continuing clozapine treatment
The 2024 Incentive Award of the Okayama Medical Association in General Medical Science (2024 Yuuki Prize)
No full textA case of retrograde colonic intussusception by tubulovillous adenoma
Full text linkIntroduction Retrograde colonic intussusception is a rare condition in adults, often caused by organic lesions such as tumors. Autonomic dysfunction in disorders like multiple system atrophy (MSA) might contribute to its occurrence.
Case presentation An 81-year-old bedridden woman with a history of MSA presented with severe abdominal pain and abdominal distension lasting 4 days. She had chronic severe constipation managed with laxatives and manual disimpaction. CT imaging revealed retrograde intussusception of the rectum into the sigmoid colon. Endoscopic reduction was attempted but was unsuccessful due to scope impassability. Emergency laparotomy identified a 4–5 cm tumor at the lead point, and manual reduction resulted in bowel perforation. Hartmann’s procedure with D2 lymphadenectomy was performed. The tumor was histopathologically diagnosed as a tubulovillous adenoma with no malignant features. The patient’s postoperative recovery was uneventful except for a urinary tract infection (Clavien–Dindo Grade II), and she was transferred to a rehabilitation facility on postoperative day 24.
Conclusion Failure of reduction by air enema should raise suspicion for retrograde intussusception, warranting prompt surgery if an organic lead point is suspected
Evaluation of a method to predict positioning errors in orthopantomography using cephalography
Full text linkIntroduction: Various radiographic examinations are used to diagnose diseases and determine treatment plans, and the quality of radiographic images affects diagnostic accuracy. This study assessed the relationship between orthopantomography and cephalometric analysis in predicting positioning errors before orthopantomography.
Methods: This study evaluated four human head phantom types and included 300 patients aged ≥18 years who underwent orthopantomography. The correlation between the Frankfort horizontal plane and occlusal plane angles in the orthopantomogram was analyzed. The occlusal plane angle at a Frankfort horizontal plane of 0° was estimated using a linear approximation formula. Frankfort horizontal plane and occlusal plane angles were measured on the cephalograms, and their differences were analyzed for correlation with the occlusal plane angle at a Frankfort horizontal plane of 0° in the corresponding orthopantomograms. The cephalogram’s condylar plane–corpus line angle was also compared with orthopantomogram measurements.
Results: Frankfort horizontal and occlusal plane angles demonstrated a strong negative correlation (r
Conclusion: Adjusting patient positioning based on individual skeletal differences and angles may reduce positioning errors and improve image quality. Cephalogram analysis could help determine an appropriate Frankfort plane angle for each patient when acquiring orthopantomograms.
Implications for practice: Integrating cephalometric analysis into positioning protocols enhances radiographic accuracy, reduces retakes, and improves diagnostic reliability in clinical positioning. This research could improve image quality by identifying reference indicators for orthopantomography by incorporating data from images other than cephalograms, such as computed tomography and magnetic resonance imaging
