Acid-electrolyzed functional water-induces Interleukin-1α release from Intracellular Storage Sites in Oral Squamous Cell Carcinoma

The aim of this study was to examine the acid-electrolyzed functional water (FW)-mediated cytokine release in an oral squamous cell carcinoma-derived cell line (OSCC) following treatment with FW. FW is generated by the electrolysis of a sodium chloride solution and accelerate the burn wound healing. To elucidate the underlying mechanisms, the cytokine/chemokine secretion profile of HSC3 cells was examined using a cytokine array. FW treatment significantly induced interleukin (IL)-1α secretion, which was confirmed by enzyme-linked immunosorbent assay. Subsequently, the HSC3 cells were pre-treated with cycloheximide (CHX) for 1 h prior to FW stimulation to determine whether the augmented IL-1α secretion was due to enhanced protein synthesis. CHX pre-treatment did not affect IL-1α secretion suggesting that the secreted IL-1α might have been derived from intracellular storage sites. The amount of IL-1α in the cell lysate of the FW-treated HSC3 cells was significantly lower than that of the non-treated cells. Immunofluorescence staining using a polyclonal antibody against full-length IL-1α revealed a drastic reduction in IL-1α inside the FW- treated cells. IL-1α is synthesized in its precursor form (pIL-1α) and cleaved to produce pro-piece and mature IL-1α (ppIL-1α and mIL-1α) inside the cells. In the present study, only pIL-1α was detected within the HSC3 cells in its resting state. However, FW stimulation resulted in the release of the 33 kDa and two other smaller forms (about 19 kDa) of the protein. These results indicates that FW treatment induces IL-1α secretion, a typical alarmin, from the intracellular storage in OSCC cells.     

ROS‐generating oxidases Nox1 and Nox4 contribute to oncogenic Ras‐induced premature senescence

Activated oncogenes induce premature cellular senescence, a permanent state of proliferative arrest in primary rodent and human fibroblasts. Recent studies suggest that generation of reactive oxygen species (ROS) is involved in oncogenic Ras‐induced premature senescence. However, the signaling mechanism controlling this oxidant‐mediated irreversible growth arrest is not fully understood. Here, we show that through the Ras/MEK pathway, Ras oncogene up‐regulated the expression of superoxide‐generating oxidases, Nox1 in rat REF52 cells and Nox4 in primary human lung TIG‐3 cells, leading to an increase in intracellular level of ROS. Ablation of Nox1 and Nox4 by small interfering RNAs (siRNAs) blocked the RasV12 senescent phenotype including β‐galactosidase activity, growth arrest and accumulation of tumor suppressors such as p53 and p16^Ink4a. This suggests that Nox‐generated ROS transduce senescence signals by activating the p53 and p16^Ink4a pathway. Furthermore, Nox1 and Nox4 siRNAs inhibited both Ras‐induced DNA damage response and p38MAPK activation, whereas overexpression of Nox1 and Nox4 alone was able to induce senescence. The involvement of Nox1 in Ras‐induced senescence was also confirmed with embryonic fibroblasts derived from Nox1 knockout mice. Together, these findings suggest that Nox1‐ and Nox4‐generated ROS play an important role in Ras‐induced premature senescence, which may involve DNA damage response and p38MAPK signaling pathways.     

Schwannoma mimicking pancreatic carcinoma: A case report

BACKGROUNDSchwannoma of the pancreas is extremely rare. We report a case of pancreatic schwannoma that was difficult to distinguish from pancreatic carcinoma before surgery.CASE SUMMARYA 66-year-old male underwent a right-lobe hepatectomy for hepatocellular carcinoma. Post-surgical computed tomography showed a 10 mm long solid mass with ischemia, with no expansion into the main pancreatic duct. Upon magnetic resonance cholangiopancreatography, the tumor had high signal intensity in diffusion weighted images, consistent with pancreatic carcinoma. Endoscopic ultrasound (EUS) was performed to obtain more information about the tumor, and showed a 14 mm solid and hypoechoic mass in the pancreatic body. Contrast enhanced EUS revealed that the tumor showed a hyperechoic mass in the early phase, and the contrasting effect continuation was very short; findings also consistent with pancreatic carcinoma. Thus, we preoperatively diagnosed his condition as a pancreatic carcinoma and performed distal pancreatectomy with splenectomy. Microscopic examination showed that the tumor was in fact a benign schwannoma. Histology showed a proliferation of spindle-shaped cell in a vague fascicular and haphazard pattern, with palisading arrangement.CONCLUSIONSchwannoma of the pancreas is very rare, however, clinicians should consider schwannoma as the differential diagnosis for pancreatic tumors.     

The feasibility of a noise elimination method using continuous wave response of therapeutic ultrasound signals for ultrasonic monitoring of high-intensity focused ultrasound treatment

Purpose

In this study, the robustness and feasibility of a noise elimination method using continuous wave response of therapeutic ultrasound signals were investigated when tissue samples were moved to simulate the respiration-induced movements of the different organs during actual high-intensity focused ultrasound (HIFU) treatment. In addition to that, the failure conditions of the proposed algorithm were also investigated.

Methods

The proposed method was applied to cases where tissue samples were moved along both the lateral and axial directions of the HIFU transducer to simulate respiration-induced motions during HIFU treatment, and the noise reduction level was investigated. In this experiment, the speed of movement was increased from 10 to 40 mm/s to simulate the actual movement of the tissue during HIFU exposure, with the intensity and driving frequency of HIFU set to 1.0–5.0 kW/cm² and 1.67 MHz, respectively. To investigate the failure conditions of the proposed algorithm, the proposed method was applied with the HIFU focus located at the boundary between the phantom and water to easily cause cavitation bubbles. The intensity of HIFU was set to 10 kW/cm².

Results

Almost all HIFU noise was constantly able to be eliminated using the proposed method when the phantom was moved along the lateral and axial directions during HIFU exposure. The noise reduction level (PRL in this study) at an intensity of 1.0, 3.0, and 5.0 kW/cm² was in the range of 28–32, 38–40, and 42–45 dB, respectively. On the other hand, HIFU noise was not basically eliminated during HIFU exposure after applying the proposed method in the case of cavitation generation at the HIFU focus.

Conclusions

The proposed method can be applicable even if homogeneous tissues or organs move axially or laterally to the direction of HIFU exposure because of breathing. A condition under which the proposed algorithm failed was when instantaneous tissue changes such as cavitation bubble generation occurred in the tissue, at which time the reflected continuous wave response became less steady.

     

Real‐Time Observation of Thrombus Growth Process in an Impeller of a Hydrodynamically Levitated Centrifugal Blood Pump by Near‐Infrared Hyperspectral Imaging

Understanding the thrombus formation in cardiovascular devices such as rotary blood pumps is the most important issue in developing more hemocompatible devices. The objective of this study was to develop a hyperspectral imaging (HSI) method to visualize the thrombus growth process within a rotary blood pump and investigate the optical properties of the thrombus. An in vitro thrombogenic test was conducted using fresh porcine blood and a specially designed hydrodynamically levitated centrifugal blood pump with a transparent bottom. The pump rotating at 3000 rpm circulated the blood at 1.0 L/min. The bottom surface of the pump was illuminated with white light pulsed at the same frequency as the pump rotation, and the backward‐scattered light was imaged using the HSI system. Using stroboscopic HSI and an image construction algorithm, dynamic spectral imaging at wavelengths ranging from 608 to 752 nm within the rotating pump was achieved. After completing the experiment, we collected the red thrombus formed in the pump impeller and quantified the thrombus hemoglobin concentration (Hb_thrombus). The spectrum changed around the center of the impeller, and the area of change expanded toward the impeller flow path. The shape corresponded approximately to the shape of the thrombus. The spectrum change indicated that the light scattering derived from red blood cells decreased. The Hb_thrombus was 4.7 ± 1.3 g/dL versus a total hemoglobin of 13 ± 0.87 g/dL. The study revealed that Hb_thrombus was reduced by the surrounding blood flow.     

Simultaneous, clonally identical T cell expansion in tonsil and synovium in a patient with rheumatoid arthritis and chronic tonsillitis

In some patients with rheumatoid arthritis (RA), the disease improves following tonsillectomy. We describe a 28-year-old woman with treatment-resistant RA and chronic tonsillitis. Initially, her arthritis had been well controlled with methotrexate and corticosteroids, but the RA activity became difficult to control in spite of addition of bucillamine to the treatment regimen and repeated arthrocentesis with infusion of corticosteroid into her swollen joints. Closer examination revealed that the period of exacerbation of her chronic tonsillitis paralleled that of the systemic arthritis, and administration of antibiotics brought transient relief of the systemic symptoms. Her arthritis was ameliorated after successful tonsillectomy and synovectomy, with marked reduction of the serum rheumatoid factor concentration. Analysis of infiltrating T cell clones in tonsil and synovium using T cell receptor V(beta) repertoire and third complementarity-determining region size distribution analysis followed by nucleotide sequencing revealed common clonal T cell expansion in both tissues. This finding suggests the possible involvement of chronic focal infection in refractory RA.     

Granulomas of the gut in Crohn's disease

To investigate the distribution of granulomas in Crohn's disease, a step sectioning study of the surgically resected intestines was carried out. This study proved that granulomas in Crohn's disease are found in the seemingly uninvolved intestinal mucosa as well as in the affected mucosa. Granulomas in the apparently involved mucosa were close to the mucosal surface (less than 500 μm) and small (80 to 160 μm across), while in the affected mucosa they were farther away from the mucosal surface (more than 500 μm) and larger (more than 160 μm across). We emphasize that these small granulomas, namely microgranulomas, in the apparently uninvolved intestinal mucosa, are of great value in diagnosing Crohn's disease.