Adenoma mimicking intraductal papillary neoplasm of the bile duct arising in an intrahepatic biliary duplication cyst.

We report a case of a cystic liver tumour in a 47-year-old man with Peutz-Jeghers syndrome (PJS) who had undergone sclerotherapy at another hospital for a cyst in hepatic segment IV (S4) 7 years earlier. Based on the preoperative imaging findings, the patient was diagnosed with an intraductal papillary neoplasm of the bile duct. Percutaneous transhepatic portal vein embolization was performed to increase the residual liver volume, followed by resection of the three right hepatic lobes and the caudate lobe, biliary reconstruction, and portal vein reconstruction. Pathological examination revealed an adenoma arising in an intrahepatic biliary duplication cyst. Retrospectively, the preoperative diagnosis was difficult, but it aligned with previous reports of biliary duplication cysts due to its continuity with the bile duct. Additionally, intrahepatic biliary duplication cysts with tumour lesions or cases in which 18F-fluorodeoxyglucose positron emission tomography was performed have not been previously reported. Therefore, preoperatively listing this disease as a differential diagnosis was difficult. PJS and chronic inflammation associated with cyst sclerotherapy may have contributed to tumour development in the intrahepatic biliary duplication cyst.

Clinical and radiological features of immune checkpoint inhibitor-related pneumonitis in lung cancer and non-lung cancers.

OBJECTIVE: To investigate the clinical and radiological features of immune checkpoint inhibitor-related pneumonitis (ICI-P), a rare but serious pulmonary complication of cancer immunotherapy and to evaluate key differences between lung cancer (LC) and non-LC patients. METHODS: 247 patients (LC, n = 151) treated with ICI for malignancies were retrospectively screened in a single institute. The number of patients, history of other immune-related adverse events (irAE), the onset, serum KL-6 levels, and chest CT features (types of pneumonitis, symmetry, laterality, location) were recorded for the ICI-P population and compared for LC and non-LC groups. RESULTS: ICI-P was identified in 26 patients in total (LC, n = 19; non-LC, n = 7). The incidence of other irAE was significantly higher in ICI-P group (63%) compared with patients without ICI-P (34%) (p = 0.0056). An earlier onset of ICI-P was recorded in LC (78 days) compared to non-LC patients (186 days) (p = 0.0034). Serum KL-6 was significantly elevated only in the non-LC group when ICI-P was noticed (p = 0.029). Major CT findings of ICI-P, irrespective of primary disease, were organizing pneumonia pattern and ground glass opacities. LC patients commonly exhibited consolidation and traction bronchiectasis and were prone to asymmetrical shadows (p < 0.001). Non-LC patients were more likely to exhibit symmetrical infiltrations. A small fraction of both groups experienced relapse or moving patterns of ICI-P. CONCLUSION: ICI-P patients more often experienced other irAE prior to the development of ICI-P. The characteristics of ICI-P can differ in terms of the onset, KL-6 reliability, and chest CT findings between LC and non-LC patients. ADVANCES IN KNOWLEDGE: In ICI-P patients, a history of other irAE can be more frequently observed. Differences in disease onset and radiological patterns between LC and non-LC patients might be helpful to make a diagnosis of ICI-P; however, longitudinal observation of chest CT scans is advised to observe the pneumonitis activity irrespective of cancer types.

Detection of Nitric Oxide Induced by Angiotensin II Receptor Type 1 Using Soluble Guanylate Cyclase beta1 Subunit Fused to a Yellow Fluorescent Protein, Venus.

Nitric oxide (NO) is an important gaseous molecule involved in many physiological and pathophysiological processes, including the regulation of G protein-coupled receptors (GPCRs). Here, we report the development of a high-affinity method to detect NO using soluble guanylate cyclase beta1 subunit fused to Venus, a variant of yellow fluorescent protein (sGC-Venus). We measured the fluorescence intensity of sGC-Venus with and without an NO donor using purified probes. At 560 nm emission, the fluorescence intensity of sGC-Venus at 405 nm excitation was increased by approximately 2.5-fold by the NO donor, but the fluorescence intensities of sGC-Venus excited by other wavelengths showed much less of an increase or no significant increase. To measure NO in living cells, the fluorescence intensity of sGC-Venus at 405 nm excitation was normalized to that at 488 nm excitation because it showed no significant difference with or without the NO donor. In HEK293 cells overexpressing the angiotensin II receptor type 1 (AT1 receptor), the production of NO induced by activation of the AT1 receptor was detected using sGC-Venus. These data indicate that sGC-Venus will be a useful tool for visualizing intracellular NO in living cells and that NO might be a common tool to regulate GPCRs.

Azelnidipine inhibits cultured rat aortic smooth muscle cell death induced by cyclic mechanical stretch.

Acute aortic dissection is the most common life-threatening vascular disease, with sudden onset of severe pain and a high fatality rate. Clarifying the detailed mechanism for aortic dissection is of great significance for establishing effective pharmacotherapy for this high mortality disease. In the present study, we evaluated the influence of biomechanical stretch, which mimics an acute rise in blood pressure using an experimental apparatus of stretching loads in vitro, on rat aortic smooth muscle cell (RASMC) death. Then, we examined the effects of azelnidipine and mitogen-activated protein kinase inhibitors on mechanical stretch-induced RASMC death. The major findings of the present study are as follows: (1) cyclic mechanical stretch on RASMC caused cell death in a time-dependent manner up to 4 h; (2) cyclic mechanical stretch on RASMC induced c-Jun N-terminal kinase (JNK) and p38 activation with peaks at 10 min; (3) azelnidipine inhibited RASMC death in a concentration-dependent manner as well as inhibited JNK and p38 activation by mechanical stretch; and (4) SP600125 (a JNK inhibitor) and SB203580 (a p38 inhibitor) protected against stretch-induced RASMC death; (5) Antioxidants, diphenylene iodonium and tempol failed to inhibit stretch-induced RASMC death. On the basis of the above findings, we propose a possible mechanism where an acute rise in blood pressure increases biomechanical stress on the arterial walls, which induces RASMC death, and thus, may lead to aortic dissection. Azelnidipine may be used as a pharmacotherapeutic agent for prevention of aortic dissection independent of its blood pressure lowering effect.

S-nitrosylation regulates mitochondrial quality control via activation of parkin.

Parkin, a ubiquitin E3 ligase of the ring between ring fingers family, has been implicated in mitochondrial quality control. A series of recent reports have suggested that the recruitment of parkin is regulated by phosphorylation. However, the molecular mechanism that activates parkin to induce mitochondrial degradation is not well understood. Here, and in contrast to previous reports that S-nitrosylation of parkin is exclusively inhibitory, we identify a previously unrecognized site of S-nitrosylation in parkin (Cys323) that induces mitochondrial degradation. We demonstrate that endogenous S-nitrosylation of parkin is in fact responsible for activation of its E3 ligase activity to induce aggregation and degradation. We further demonstrate that mitochondrial uncoupling agents result in denitrosylation of parkin, and that prevention of denitrosylation restores mitochondrial degradation. Our data indicates that NO both positive effects on mitochondrial quality control, and suggest that targeted S-nitrosylation could provide a novel therapeutic strategy against Parkinson's disease.

Role of big mitogen-activated protein kinase 1 (BMK1) / extracellular signal-regulated kinase 5 (ERK5) in the pathogenesis and progression of atherosclerosis.

Big mitogen-activated protein kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is a newly identified member of the mitogen-activated protein (MAP) kinase family. BMK1 has been reported to be sensitive to various neuro-humoral factors and oxidative stress in various cells. In this review, we focused on the role of BMK1 in atherosclerosis in a cultured rat aortic smooth muscle cell model. Treatment with platelet-derived growth factor caused vascular smooth muscle cell (VSMC) migration in a BMK1 activation-dependent manner. H(2)O(2) caused BMK1 activation and VSMC death, including apoptosis of VSMCs. An inhibitory function for BMK1 against cell death from oxidative stress was discovered using siRNA techniques to downregulate the expression of BMK1. These findings suggest a role for BMK1 in the pathogenesis and/or progression of atherosclerosis.

Nanofiber formation via the self-assembly of a chiral regioregular poly(azomethine).

An optically active pi-conjugated poly(azomethine) can be self-assembled into nanometer-sized fibrous architectures with a unique optical activity in the film state, whereas its corresponding racemic analogue did not show any distinct self-assembling properties.