Effectiveness of deep learning-based reconstruction for improvement of image quality and liver tumor detectability in the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging.

PURPOSE: To evaluate the effectiveness of deep learning-based reconstruction (DLR) in improving image quality and tumor detectability of isovoxel high-resolution breath-hold fat-suppressed T1-weighted imaging (HR-BH-FS-T1WI) in the hepatobiliary phase (HBP) of Gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI). MATERIALS AND METHODS: This retrospective evaluated 42 patients with 98 liver tumors who underwent Gd-EOB-MRI between March 2023 and May 2023 using three techniques based on HBP imaging: isovoxel HR-BH-FS-T1WI reconstructed (1) with DLR (BH-DLR +) and (2) without DLR (BH-DLR -) and (3) HR-FS-T1WI scanned with a free-breathing technique using a navigator-echo-triggered technique and DLR (Navi-DLR +). The three techniques were qualitatively and quantitatively compared by the Friedman test and the Bonferroni post-hoc test. Tumor detectability was compared using the McNemar test. RESULTS: BH-DLR + (3.85, average score of two radiologists) showed significantly better qualitative scores for image noise than BH-DLR - (2.84) and Navi-DLR + (3.37) (p < 0.0167), and Navi-DLR + showed significantly better scores than BH-DLR - (p < 0.0167). BH-DLR + (3.77) and BH-DLR - (3.77) showed significantly better qualitative scores for respiratory motion artifact than Navi-DLR + (2.75) (p < 0.0167), but there was no significant difference in scores between BH-DLR + and BH-DLR - (p > 0.0167). BH-DLR + (0.32) and Navi-DLR + (0.33) showed significantly higher lesion-to-nonlesion CR than BH-DLR - (0.29) (p < 0.0167), but there was no significant difference in lesion-to-nonlesion CR between BH-DLR + and Navi-DLR + (p > 0.0167). BH-DLR + (89.8%) showed significantly better tumor detectability than BH-DLR - (76.0%) and Navi-DLR + (77.6%) (p < 0.05). CONCLUSION: The use of DLR for isovoxel HR-BH-FS-T1WI was effective in improving image quality and tumor detectability.

Oxytocin receptor-expressing neurons in the medial preoptic area are essential for lactation, whereas those in the lateral septum are not critical for maternal behavior.

INTRODUCTION: In nurturing systems, the oxytocin (Oxt)-oxytocin receptor (Oxtr) system is important for parturition, and essential for lactation and parental behavior. Among the nerve nuclei that express Oxtr, the lateral septal nucleus (LS) and medial preoptic area (MPOA) are representative regions that control maternal behavior. METHODS: We investigated the role of Oxtr- and Oxtr-expressing neurons, located in the LS and MPOA, in regulating maternal behavior by regulating Oxtr expression in a region-specific manner using recombinant mice and adeno-associated viruses. We quantified the prolactin (Prl) concentrations in the pituitary gland and plasma when Oxtr expression in the MPOA was reduced. RESULTS: The endogenous Oxtr gene in the neurons of the LS did not seem to play an essential role in maternal behavior. Conversely, decreased Oxtr expression in the MPOA increased the frequency of pups being left outside the nest and reduced their survival rate. Deletion of Oxtr in MPOA neurons prevented elevation of Prl levels in plasma and pituitary at postpartum day 2. DISCUSSION/CONCLUSION: Oxtr-expressing neurons in the MPOA are involved in the postpartum production of Prl. We confirmed the essential functions of Oxtr-expressing neurons and the Oxtr gene itself in the MPOA for the sustainability of maternal behavior, which involved Oxtr-dependent induction of Prl.

Preoperatively diagnosed intraductal oncocytic papillary neoplasm of the pancreas with prominent invasion: a case report.

Previously considered as one of the less-invasive subtypes of intraductal papillary mucinous neoplasm, intraductal oncocytic papillary neoplasm (IOPN) has recently been acknowledged as a new entity of pancreatic tumor. We herein present a case of preoperatively diagnosable IOPN invasion in the stomach and colon. A 78-year-old woman was referred to our hospital for evaluation of anorexia and gastroesophageal reflux. Upper gastrointestinal endoscopy revealed a gastric subepithelial lesion with ulcerated mucosa that required hemostasis. Computed tomography revealed a 96-mm-diameter solid tumor with a well-defined border and centrally positioned necrotic area, extending from the stomach to the transverse colon and pancreatic tail. Because it was suspected to be a pancreatic solid tumor with direct stomach invasion, endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) was performed, which led to a preoperative diagnosis of IOPN. Moreover, laparoscopic pancreatosplenectomy, proximal gastrectomy, and transverse colectomy were performed. Analysis of the surgical specimen revealed that the tumor was IOPN and had invaded the stomach and transverse colon. Lymph node metastasis was also confirmed. These findings indicate that IOPN can manifest as an invasive tumor, and EUS-FNB may be equally helpful for assessing the invaded area of a cystic lesion as it is for a solid lesion.

Unique image findings around "kissing" distal anterior cerebral artery aneurysms in addition to perianeurysmal edema: A case report.

Background: Some aneurysms cause edema formation in the surrounding brain parenchyma and are thought to reflect various phenomena occurring in the aneurysm. Some authors highlighted perianeurysmal edema (PAE) as a finding that indicates higher risk of rupture of the aneurysm. On the other hand, there are no reports of image changes in the surrounding brain parenchyma of aneurysm other than edema formation. Case Description: We describe a 63-year-old man with unique signal change in the surrounding brain parenchyma of "kissing" distal anterior cerebral artery aneurysms completely different from PAE. The large and partially thrombosed aneurysm presented well-defined signal change surrounding brain parenchyma in addition to PAE. Intraoperative findings revealed the signal change as a space of retaining serous fluid. Drain the fluid and clipping was made for the both anterior cerebral artery aneurysms. The postoperative course was uneventful and his headache was improved the day after the surgery. The perianeurysmal signal change was also disappeared immediately after the surgery except for the PAE. Conclusion: This case demonstrates a rare phenomenon of signal change around the aneurysm, and there is a possibility that the unique finding exists as an early manifestation of intracerebral hematoma associated with aneurysm rupture.

Intraductal oncocytic papillary neoplasm of the pancreas: clinical and radiological features compared to those of intraductal papillary mucinous neoplasm.

PURPOSE: This study aimed to characterize the clinical and imaging findings of intraductal oncocytic papillary neoplasm of the pancreas (IOPN-P) compared to those of intraductal papillary mucinous adenoma/carcinoma (IPMA/IPMC). METHODS: This multi-institutional retrospective study reviewed the clinical, imaging, and pathological findings of 21 patients with pathologically proven IOPN-P. Twenty-one computed tomography (CT) and magnetic resonance imaging, and seven 18F-fluorodeoxyglucose (FDG)-positron emission tomography were performed before surgery. The following findings were evaluated: preoperative blood test results, lesion size and location, pancreatic duct diameter, contrast-enhancement effect, bile duct and peripancreatic invasion, maximum standardized uptake (SUVmax) value, and pathological stromal invasion. RESULTS: Serum carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA19-9) levels were significantly higher in the IPMN/IPMC group than in the IOPN-P group. Except in one patient, IOPN-P showed multifocal cystic lesions with solid components or a tumor in the main pancreatic duct (MPD) with dilatation. IOPN-P had a higher frequency of solid parts and a lower frequency of downstream MPD dilatation than IPMA. IPMC showed smaller overall cyst size, more radiological peripancreatic invasion, and worse recurrence-free and overall survival than IOPN-P. The average SUVmax value of IOPN-P was 7.5. Pathologically, 17 of the 21 IOPN-Ps had a malignant component, and six showed stromal invasion. CONCLUSION: IOPN-P shows cystic-solid lesions similar to IPMC but has lower serum CEA and CA19-9 levels, larger overall cyst size, lower frequency of peripancreatic invasion, and more favorable prognosis than IPMC. Moreover, the high FDG uptake by IOPN-Ps may be a characteristic finding of this study.

Fusion imaging of single-photon emission computed tomography and magnetic resonance lymphangiography for post-Fontan chylothorax.

A preschool male patient with an extensive cardiac surgical history developed refractory chylothorax after a total cavopulmonary connection. Neither lymphoscintigraphy nor single-photon emission computed tomography (SPECT)/computed tomography could identify the lymphatic system leakage sites. Non-contrast heavy T2-weighted magnetic resonance lymphangiography (MRL) was performed to visualize the lymphatic system. Nevertheless, distinguishing lymphatic ducts from other watery structures of the patient remained difficult. Therefore, non-contrast MRL and SPECT images were fused. This hybrid diagnostic tool elucidated the pathophysiology of the prolonged chylothorax; pulmonary lymphatic perfusion syndrome and illustrated the anatomical connection of the thoracic duct and an abnormally dilated lymphatic network in the neck and left hilar regions. Subsequent intranodal lymphangiography with ethiodized oil confirmed these findings. SPECT/MRL may become an alternative modality for revealing the mechanism of prolonged chylothorax by visualizing the lymphatic system when dynamic contrast-enhanced magnetic resonance lymphangiography is unavailable.

Catheter Intervention for Flow Regulatory Clips on Palliative Shunts and Conduits in Patients with Congenital Heart Disease.

Catheter intervention (CI) for a Blalock-Taussig shunt (BTS) or a ventricle-to-pulmonary artery conduit (VPC) is often required after a palliative surgery for congenital heart disease. Flow regulatory clips help improve interstage mortality; their use necessitates CIs to prevent cyanosis. To study the CI outcomes in patients who underwent palliative surgery with either BTSs or VPCs with flow regulatory clips. This single-center retrospective study evaluated demographic characteristics and interventional outcomes of 49 consecutive pediatric patients who required CI for BTS (BTS group) or VPC (VPC group) between January 2008 and September 2018. Overall, 34 and 18 procedures were performed in the BTS and VPC groups, respectively. Moreover, 19/32 (59.3%) and 12/17 (70.1%) patients from the BTS and VPC groups had flow regulatory clips, respectively. All clips were unclipped successfully; one patient in each group underwent staged unclipping. A higher proportion of "clipped patients" underwent CI due to desaturation [clipped vs. non-clipped: BTS, 10/20 (50.0%) vs. 3/14 (21.4%), p = 0.092; VPC, 9/13 (69.2%) vs. 1/5 (20.0%), p = 0.060]. Most clipped patients successfully progressed to the next stage [BTS, 19/20 (95.0%); VPC, 12/13 (92.3%)]. Severe adverse events (SAEs) were more frequent in the VPC group than in the BTS group [3/13 (23.1%) vs. 0/20 (0%), p = 0.024]. Two patients developed an atrioventricular block (requiring an atropine infusion), while one died due to pulmonary overcirculation. While the indication of CI was cyanosis for a higher proportion of clipped patients, all clips were unclipped successfully. The incidence of CI-related SAEs was higher in the VPC group than in the BTS group.

Deep learning-based magnetic resonance imaging reconstruction for improving the image quality of reduced-field-of-view diffusion-weighted imaging of the pancreas.

BACKGROUND: It has been reported that deep learning-based reconstruction (DLR) can reduce image noise and artifacts, thereby improving the signal-to-noise ratio and image sharpness. However, no previous studies have evaluated the efficacy of DLR in improving image quality in reduced-field-of-view (reduced-FOV) diffusion-weighted imaging (DWI) [field-of-view optimized and constrained undistorted single-shot (FOCUS)] of the pancreas. We hypothesized that a combination of these techniques would improve DWI image quality without prolonging the scan time but would influence the apparent diffusion coefficient calculation. AIM: To evaluate the efficacy of DLR for image quality improvement of FOCUS of the pancreas. METHODS: This was a retrospective study evaluated 37 patients with pancreatic cystic lesions who underwent magnetic resonance imaging between August 2021 and October 2021. We evaluated three types of FOCUS examinations: FOCUS with DLR (FOCUS-DLR+), FOCUS without DLR (FOCUS-DLR-), and conventional FOCUS (FOCUS-conv). The three types of FOCUS and their apparent diffusion coefficient (ADC) maps were compared qualitatively and quantitatively. RESULTS: FOCUS-DLR+ (3.62, average score of two radiologists) showed significantly better qualitative scores for image noise than FOCUS-DLR- (2.62) and FOCUS-conv (2.88) (P < 0.05). Furthermore, FOCUS-DLR+ showed the highest contrast ratio (CR) between the pancreatic parenchyma and adjacent fat tissue for b-values of 0 and 600 s/mm2 (0.72 ± 0.08 and 0.68 ± 0.08) and FOCUS-DLR- showed the highest CR between cystic lesions and the pancreatic parenchyma for the b-values of 0 and 600 s/mm2 (0.62 ± 0.21 and 0.62 ± 0.21) (P < 0.05), respectively. FOCUS-DLR+ provided significantly higher ADCs of the pancreas and lesion (1.44 ± 0.24 and 3.00 ± 0.66) compared to FOCUS-DLR- (1.39 ± 0.22 and 2.86 ± 0.61) and significantly lower ADCs compared to FOCUS-conv (1.84 ± 0.45 and 3.32 ± 0.70) (P < 0.05), respectively. CONCLUSION: This study evaluated the efficacy of DLR for image quality improvement in reduced-FOV DWI of the pancreas. DLR can significantly denoise images without prolonging the scan time or decreasing the spatial resolution. The denoising level of DWI can be controlled to make the images appear more natural to the human eye. However, this study revealed that DLR did not ameliorate pancreatic distortion. Additionally, physicians should pay attention to the interpretation of ADCs after DLR application because ADCs are significantly changed by DLR.

[Elucidation and Application of Novel Action of Therapeutic Agents for Diabetic Neuropathy].

Epalrestat is the only aldose reductase inhibitor that is currently available for diabetic peripheral neuropathy. Oxidative stress impairs endothelial cells, thereby leading to numerous pathological conditions. Increasing antioxidative ability is important to prevent cellular toxicity induced by reactive oxygen species. Epalrestat increases antioxidant defense factors such as glutathione and γ-glutamylcysteine ligase in vascular endothelial cells through activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). This increases suppression of oxidative stress-induced cellular toxicity. Cadmium is an industrial and environmental pollutant that targets the vascular endothelium. The vascular system is critically affected by cadmium toxicity. Therapeutic treatment against cadmium toxicity is chelation therapy that promotes metal excretion; however, cadmium chelators can cause renal toxicity. Therefore, safe and efficient therapeutic agents are required. Epalrestat suppresses cadmium-induced cytotoxicity in vascular endothelial cells through activation of Nrf2. In addition, epalrestat affects the intracellular levels of cadmium, cadmium transporter Zrt-Irt-like protein 8 (ZIP8), and metallothionein (MT). The upregulation of ZIP8 and MT may be involved in the suppression of cadmium-induced cytotoxicity by epalrestat. Drug repurposing is a new strategy for drug discovery in which the pharmacological action of existing medicines whose safety and pharmacokinetics have already been confirmed clinically and whose use has been approved is examined comprehensively at the molecular level. The results can be applied to the development of existing drugs for use as medicines for the treatment of other diseases. This review provides useful findings for future expansion of indications as research leading to drug repurposing of epalrestat.

Oral Administration of Mulberry (Morus alba L.) Leaf Powder Prevents the Development of Hepatocellular Carcinoma in Stelic Animal Model (STAM) Mice.

BACKGROUND/AIM: We examined the inhibitory effect of mulberry leaf (ML) (Morus alba L.) administration on the development of hepatocellular carcinoma (HCC) in stelic animal model (STAM) mice. This STAM mouse model of nonalcoholic steatohepatitis (NASH) closely resembles the progression from NASH to HCC in human clinical practice. MATERIALS AND METHODS: Streptozotocin (STZ, 200 µg) was administered to C57L/6J mice that were fed a high-fat diet (HFD; STAM mice) with 1% ML ad libitum. After sacrificing, the liver and blood were collected. Biochemical tests of plasma and histologic examination of the liver were performed. RESULTS: Pathologic examination of all (6/6) liver samples of the STAM mice showed HCC. On the contrary, in STAM mice that received ML, fat deposition and adenoma were observed in 6/6 and 2/6 of the liver samples, respectively, but there was no HCC. CONCLUSION: Administration of ML in STAM mice inhibited the progression from nonalcoholic hepatitis (NASH) to HCC. ML may be effective in preventing the development of HCC.

Effect of Chloroquine on Doxorubicin-induced Apoptosis in A549 Cells.

BACKGROUND/AIM: We investigated the effects of chloroquine, an autophagy inhibitor, on doxorubicin-induced apoptosis in A549 cells. MATERIALS AND METHODS: A549 cells were treated with doxorubicin, chloroquine, or both. Then, cytotoxicity was measured. The expression levels of caspases and mitogen-activated protein kinases were also quantified. In addition, the levels of doxorubicin-derived reactive oxygen species were measured. RESULTS: Chloroquine enhanced doxorubicin-induced apoptosis and oxidative stress and suppressed the doxorubicin-induced extracellular-signal-regulated kinase activation. CONCLUSION: Chloroquine enhances doxorubicin-induced and oxidative stress-mediated apoptosis. This mechanism may involve the dephosphorylation of extracellular-signal-regulated kinases.

What is the "washout" of hepatocellular carcinoma as observed on the equilibrium phase CT?: consideration based on the concept of extracellular volume fraction.

PURPOSE: To verify the hypothesis that extracellular volume fraction (ECV) and precontrast CT density are the main determinants of washout of hepatocellular carcinoma (HCC) at the equilibrium phase CT. MATERIALS AND METHODS: Between 2018 and 2020, patients with surgically resected HCC were recruited who had undergone preoperative 4-phase CT. Those larger than 6 cm were excluded to minimize the possibility of intratumoral hemorrhage or degeneration. Two radiologists reviewed the whole images in consensus and divided cases into washout positive and negative groups. Washout positive group at the equilibrium phase was defined as "HCC showing relatively low density as compared to the surrounding background liver (BGL), irrespective of the presence of early enhancement or fibrous capsule". Several clinico-pathological and radiological features, including ECV and precontrast CT density, were correlated to the presence of washout, using uni- and multi-variable analyses. RESULTS: 27 HCC in 24 patients met the inclusion criteria. 22 (82%) and five HCC belonged to washout positive and negative groups, respectively. Univariable analysis revealed ECV of HCC and BGL, ECV difference between HCC and BGL, and presence of fibrous capsule on the equilibrium phase CT were the significant factors. Multivariable analysis showed ECV of HCC and BGL, and precontrast CT density of BGL, were the independently significant factors related to washout, suggesting washout is more likely observed with lower HCC ECV, higher BGL ECV, and higher BGL precontrast CT density. CONCLUSION: Major determinants of washout of HCC may be ECV of HCC and BGL, and precontrast CT density of BGL.

First case of a renal cyst infection caused by Desulfovibrio: a case report and literature review.

BACKGROUND: Genus Desulfovibrio species is a sulphate-reducing anaerobic gram-negative rod that resides in the human oral cavity and intestinal tract. It was reported as the causative pathogen of bacteraemia and abdominal infections, but not renal cyst infection, and Desulfovibrio fairfieldensis has higher pathogenicity than other Desulfovibrio species. CASE PRESENTATION: A 63-year-old man was on haemodialysis for end-stage renal failure due to autosomal dominant polycystic kidney disease. On admission, he had a persistent high-grade fever, right lumbar back pain, and elevated C-reactive protein levels. His blood and urine cultures were negative. He received ciprofloxacin and meropenem; however, there was no clinical improvement. Contrast-enhanced computed tomography and plain magnetic resonance imaging revealed a haemorrhagic cyst at the upper pole of the right kidney. The lesion was drained. Although the drainage fluid culture was negative, D. fairfieldensis was detected in a renal cyst using a polymerase chain reaction. After the renal cyst drainage, he was treated with oral metronidazole and improved without any relapse. CONCLUSIONS: To the best of our knowledge, this is the first reported case of a renal cyst infection with Desulfovibrio species. D. fairfieldensis is difficult to detect, and polymerase chain reaction tests can detect this bacterium and ensure better management for a successful recovery.

A case of primary histiocytic sarcoma arising from a neck lymph node.

Histiocytic sarcoma (HS) is an aggressive and rare hematological malignancy. Its treatment has not been established, and most patients die within 2 years of diagnosis. Resection can provide a favorable prognosis for solitary lesions. We present the case of an 80-year-old Japanese man with HS. He presented a history of a slow-growing painless mass in the lower part of his right jaw. Ultrasonography showed a swollen lymph node in the vicinity of the right submandibular gland. Contrast-enhanced computed tomography revealed a heterogeneous, low-contrast mass on the right of the neck. Magnetic resonance imaging revealed a heterogeneously enhanced mass in gadolinium-enhanced T1-weighted images. The fine needle biopsy showed spindle-shaped cells and HS was suspected. Fluorodeoxyglucose positron emission tomography revealed uptake by the tumor alone. The patient underwent right upper neck dissection and resection of the submandibular salivary glands. No postoperative adjuvant treatment was administered, but 2-year survival was achieved. Histopathological examination showed proliferation of large, pleomorphic atypical cells without differentiation into lymphocytes, which proved their differentiation into histiocytes. A bone marrow biopsy showed no evidence of monocytic leukemia. Thus, a diagnosis of HS was made. With local treatment alone, our patient achieved long-term survival, maintaining his quality of life.

Prognostic factors to predict the survival in patients with advanced gastric cancer who receive later-line nivolumab monotherapy-The Asahikawa Gastric Cancer Cohort Study (AGCC).

BACKGROUND: Chemotherapy for advanced gastric cancer is recommended in the guidelines; however, later-line treatment remains controversial. Since immune checkpoint inhibitors have been used for the treatment of various malignancies, trials have been performed for gastric cancer. A phase 3 trial indicated the survival benefit of nivolumab monotherapy for gastric cancer patients treated with prior chemotherapy regimens. PATIENTS AND METHODS: A regional cohort study was undertaken to determine the real-world data of nivolumab treatment for patients with advanced or recurrent gastric cancer. The patients were enrolled for 2 years from October 2017 to October 2019 and were prospectively followed for 1 year to examine the overall survival (OS). The patient characteristics were analyzed in a multivariate analysis and a nomogram to predict the probability of survival was generated. RESULTS: In total, 70 patients who received nivolumab as ≥third-line chemotherapy were included in the Asahikawa Gastric Cancer Cohort. The median OS was 7.5 (95% CI, 4.8-10.2) months and the response rate was 18.6%. Diffuse type classification, bone metastasis, high neutrophil/lymphocyte ratio, and high CRP were associated with poor OS/prognosis in the multivariate analysis. A nomogram was developed based on these clinical parameters and the concordance index was 0.80 (95% CI, 0.68-0.91). The responders were aged and were frequently diagnosed with intestinal type gastric cancer, including patients with a HER2-positive status (27.3%) or microsatellite instability-high (27.3%) status. CONCLUSIONS: The regional cohort study of nivolumab monotherapy for gastric cancer patients revealed prognostic factors and a nomogram was developed that could predict the probability of survival.

Evaluation of Global DNA Methylation and Gene Expression of Izumo1 and Izumo1r in Gonads after High- and Low-Dose Radiation in Neonatal Mice.

The intergenerational effects from chronic low-dose exposure are matters of concern. It is thus important to elucidate the radiation-induced effects of germ cell maturation, fertilization and embryonic development. It is well known that DNA methylation levels in CpG sites in gametes are reprogrammed in stages during their maturity. Furthermore, the binding of Izumo on the surface of sperm and Juno on the surface of oocytes is essential for fertilization. Thus, there is a possibility that these genes are useful indicators to evaluate fertility in mice after irradiation exposure. Therefore, in this study, we analyzed global DNA methylation patterns in the testes and gene expression of Izumo1 and Izumo1r (Juno) in the gonads of mice after neonatal acute high-dose ionizing radiation (HDR) and chronic low-dose ionizing radiation (LDR). One-week-old male and female mice were irradiated with a total dose of 4 Gy, with acute HDR at 7 days at a dose rate of 30 Gy/h and LDR continuously at a dose rate of 6 mGy/h from 7 to 35 days. Their gonads were subsequently analyzed. The results of global DNA methylation patterns in the testes showed that methylation level increased with age in the control group, the LDR group maintained its DNA methylation level, and the HDR group showed decreased DNA methylation levels with age. In the control group, the gene expression level of Izumo1 in the testis did not show age-related changes, although there was high expression at 100 days of age. However, in the LDR group, the expression level recovered after the end of irradiation, while it remained low regardless of age in the HDR group. Conversely, gene expression of Izumo1r (Izumo1 receptor) in the ovary decreased with age in the control group. Although the gene expression of Izumo1r decreased with age in the LDR group, it remained low in the HDR group. Our results indicate that LDR can induce different DNA methylation patterns, and both high- and low-dose radiation before sexual maturity might affect gametogenesis and fertility.

[Pulmonary Epithelioid Hemangioendothelioma:Report of a Case].

A 54-year-old woman with a lung tumor was admitted to our hospital for surgical treatment. Chest computed tomography (CT) showed a 16×14×10 mm nodule in left upper lobe. Flurodeoxyglucose (FDG)-positron emission tomography (PET)/CT revealed increased uptake in the nodule. We diagnosed the tumor as lung cancer preoperatively, and performed surgery. Frozen section diagnosis after partial lung resection was lung cancer and we performed left upper lobectomy. The tumor was histopathologically diagnosed as pulmonary epithelioid hemangioendothelioma( PEH).

Oral Pathobiont-Induced Changes in Gut Microbiota Aggravate the Pathology of Nonalcoholic Fatty Liver Disease in Mice.

Background & Aims: Periodontitis increases the risk of nonalcoholic fatty liver disease (NAFLD); however, the underlying mechanisms are unclear. Here, we show that gut dysbiosis induced by oral administration of Porphyromonas gingivalis, a representative periodontopathic bacterium, is involved in the aggravation of NAFLD pathology. Methods: C57BL/6N mice were administered either vehicle, P. gingivalis, or Prevotella intermedia, another periodontopathic bacterium with weaker periodontal pathogenicity, followed by feeding on a choline-deficient, l-amino acid-defined, high-fat diet with 60 kcal% fat and 0.1% methionine (CDAHFD60). The gut microbial communities were analyzed by pyrosequencing the 16S ribosomal RNA genes. Metagenomic analysis was used to determine the relative abundance of the Kyoto Encyclopedia of Genes and Genomes pathways encoded in the gut microbiota. Serum metabolites were analyzed using nuclear magnetic resonance-based metabolomics coupled with multivariate statistical analyses. Hepatic gene expression profiles were analyzed via DNA microarray and quantitative polymerase chain reaction. Results: CDAHFD60 feeding induced hepatic steatosis, and in combination with bacterial administration, it further aggravated NAFLD pathology, thereby increasing fibrosis. Gene expression analysis of liver samples revealed that genes involved in NAFLD pathology were perturbed, and the two bacteria induced distinct expression profiles. This might be due to quantitative and qualitative differences in the influx of bacterial products in the gut because the serum endotoxin levels, compositions of the gut microbiota, and serum metabolite profiles induced by the ingested P. intermedia and P. gingivalis were different. Conclusions: Swallowed periodontopathic bacteria aggravate NAFLD pathology, likely due to dysregulation of gene expression by inducing gut dysbiosis and subsequent influx of gut bacteria and/or bacterial products.

Effects of Kumaizasa (Sasa senanensis) Leaf Extract on Innate Immune Regulation in HEK293 Cells and Macrophages.

BACKGROUND/AIM: We investigated the effect of Kumaizasa leaf extract (KLE) on innate immunity using the HEK293 and RAW 264.7 cell lines. MATERIALS AND METHODS: KLE, lipopolysaccharides (LPS), or KLE with LPS were added to RAW 264.7 cells. The TNF-α and IL-1ß mRNA expression was then quantified. The expression of MAPKs, NFĸB, TNF-α and IL-1ß proteins was also quantified. In addition, KLE was added to HEK293 cells and the IL-8 concentration was measured. RESULTS: In RAW 264.7 cells, KLE increased the levels of TNF-α and IL-1ß mRNA. By contrast, when KLE and LPS were added to RAW 264.7 cells, the increase in TNF-α and IL-1ß mRNA was ameliorated. Similarly, the expression of JNK and ERK proteins was reduced. The addition of KLE to HEK293 cells induced IL-8 production. CONCLUSION: Based on these results, a KLE-mediated mechanism may regulate immunity by suppressing the expression of JNK and ERK, which are involved in inflammatory signal transduction.

Development of nanobody-based POLArIS orientation probes enabled multi-color/multi-target orientation imaging in living cells.

Fluorescence polarization microscopy (FPM) can visualize the dipole orientation of fluorescent molecules and has been used for analyzing architectural dynamics of biomolecules including cytoskeletal proteins. To monitor the orientation of target molecules by FPM, target molecules need to be labeled with fluorophores in a sterically constrained manner, so that the fluorophores do not freely rotate. Recently, a versatile probe for such labeling using fluorescent proteins, POLArIS (Probe for Orientation and Localization Assessment, recognizing specific Intracellular Structures of interest), was reported. POLArIS is a fusion protein consisting of a non-immunoglobulin-based recombinant binder Affimer and a green fluorescent protein (GFP), where the Affimer and GFP are rigidly connected to each other. POLArIS probe for molecules of interest can be developed through phage display screening of Affimer. This screening is followed by the rigid connection of fluorescent proteins to the selected Affimers. The Affimer-based POLArIS, however, cannot be used with animal immune libraries for selecting specific binder clones. In addition, multi-color FPM by POLArIS was not available due to the lack of color variations of POLArIS. In this study, we have developed new versions of POLArIS with nanobodies, which are compatible with animal immune libraries, and expanded color variations of POLArIS with cyan/green/yellow/red fluorescent proteins, enabling multi-color orientation imaging for multiple targets. Using nanobody-based POLArIS orientation probes, we performed two-color FPM of F-actin and vimentin in living cells. Furthermore, we made nanobody-based POLArIS probes that have different dipole orientations for adjusting the orientation of fluorescence polarization with respect to the target molecules. These nanobody-based POLArIS with options of colors and dipole orientations will enhance the performance of this probe for broader applications of fluorescence polarization imaging in living cells, tissues, and whole organisms.