Acanthopanax senticosus ameliorates steatohepatitis through HNF4 alpha pathway activation in mice.

Non-alcoholic fatty liver disease is a common liver disease worldwide, and is associated with dysregulation of lipid metabolism, leading to inflammation and fibrosis. Acanthopanax senticosus Harms (ASH) is widely used in traditional medicine as an adaptogen food. We examined the effect of ASH on steatohepatitis using a high-fat diet mouse model. Mice were fed a choline-deficient, L-amino acid-defined, high-fat diet with ASH extract (ASHE). After 6 weeks, liver RNA transcriptome sequencing (RNA-Seq) was performed, followed by Ingenuity Pathway Analysis (IPA). Our findings revealed that mice fed a high-fat diet with 5% ASHE exhibited significantly reduced liver steatosis. These mice also demonstrated alleviated inflammation and reduced fibrosis in the liver. IPA of RNA-Seq indicated that hepatocyte nuclear factor 4 alpha (HNF4 alpha), a transcription factor, was the activated upstream regulator (P-value 0.00155, z score = 2.413) in the liver of ASHE-fed mice. Adenosine triphosphate binding cassette transporter 8 and carboxylesterase 2, downstream targets of HNF4 alpha pathway, were upregulated. Finally, ASHE-treated HepG2 cells exposed to palmitate exhibited significantly decreased lipid droplet contents. Our study provides that ASHE can activate HNF4 alpha pathway and promote fat secretion from hepatocytes, thereby serving as a prophylactic treatment for steatohepatitis in mice.

Poor Prognosis in Patients With Stage III Colorectal Cancer Receiving Adjuvant FOLFOX/CAPOX Therapy Is Predicted by the Presence of Many Poorly Differentiated Clusters.

BACKGROUND/AIM: Poorly differentiated clusters (PDCs) have been reported to be a useful grading system for predicting prognosis in patients with colorectal cancer (CRC). We investigated the association between the number of PDCs and prognosis in patients with stage III CRC treated with oxaliplatin-based adjuvant chemotherapy. PATIENTS AND METHODS: This is a retrospective study of 49 patients with stage III CRC who underwent curative surgery followed by oxaliplatin-based adjuvant chemotherapy. PDC was defined as a cluster of ≥5 cancer cells without glandular structure at the invasive front of the primary tumor. RESULTS: During the observation period, 12 patients experienced relapse. The patients were divided into two groups (<7 and ≥7 PDC groups), and receiver operating characteristic (ROC) curves were calculated [area under the curve (AUC)=0.743]. Patients with ≥7 PDCs had a much shorter relapse-free survival (RFS) than those with <7 PDCs (p<0.0001). The overall survival (OS) was also significantly worse in patients with ≥7 PDCs than in those with <7 PDCs (p<0.0001). Multivariate analysis revealed that PDC was the only significant prognostic factor measured that could predict RFS (p=0.002) and OS (p=0.0047) in patients with stage III CRC treated with oxaliplatin-based adjuvant chemotherapy. CONCLUSION: In patients with stage III CRC treated with post-resection oxaliplatin-based adjuvant chemotherapeutic regimens, the presence of ≥7 PDCs at the invasive front of the primary tumor predicted unfavorable prognosis.

[A Case of Pancreas Neuroendocrine Carcinoma Achieved Long-Term Survival by Carboplatin plus Etoposide Therapy].

A 70-year-old man with the history of diabetes mellitus complained of lower abdominal discomfort. Abdominal ultrasonography revealed a pancreatic mass. Contrast enhanced CT showed a 2.6 cm-enhanced tumor ventral to the pancreatic head. It was diagnosed with a pancreatic neuroendocrine carcinoma(PanNEC-G3)by EUS-FNA. The patient underwent pancreatoduodenectomy with the wedge resection of the portal vein and partial resection of the transverse colon. We administered 6 cycles of adjuvant therapy with CDDP plus CPT-11. With the presentation of lymph node metastases and the local recurrence in the anastomotic site of the transverse colon 15 months after surgery, the patient received carboplatin plus etoposide(CE)therapy. Although local recurrence completely responded to the CE therapy, bone metastases were detected 27 months after surgery. Metastatic lesion did not respond to systemic chemotherapy including gemcitabine plus nab-paclitaxel and nal-IRI plus 5-FU/LV, and the patient eventually died 37 months after the surgery. PanNECs represent for less than 1% of all pancreatic tumor. They are characterized by high malignant potential and short time survival with the reported OS of 8.5 to 21 months. This case served as an important reminder to consider multimodal treatment for PanNEC patients to obtain longer survival.

Effects of audio and visual distraction on patients' vital signs and tolerance during esophagogastroduodenoscopy: a randomized controlled trial.

BACKGROUND: Esophagogastroduodenoscopy (EGD) provides an indispensable and unambiguous inspection allowing the discovery upper gastrointestinal lesions. However, many patients are anxious about undergoing EGD. Few studies have investigated the influence on patients' vital signs and tolerance during EGD using subjective and objective assessments. This study was a prospective randomized controlled study that investigated the influence of audio and visual distraction on EGD. METHODS: We randomly divided 289 subjects who underwent EGD into 4 groups (control group, audio group, visual group, combination group) and examined their vital signs, heart rate variability (HRV), psychological items, and acceptance of distraction. RESULTS: Pulse rate (PR) at post-distraction and post-EGD in the 3 distraction groups were significantly lower than those of control group (p <  0.001 and p <  0.01, respectively). Blood pressure (BP) during and post-EGD was significantly higher than that at pre-EGD in control group (p <  0.05), but no significant elevation of BP was observed during the latter half of EGD and post-EGD in the 3 distraction groups. BP at post-distraction improved significantly compared to pre-distraction in the 3 distraction groups (p <  0.05). There was a significant difference in the low-frequency (LF) power/ high-frequency (HF) power at post-distraction and post-EGD among the 4 groups (p <  0.001 and p <  0.001, respectively). The LF power/HF power at post-distraction and post-EGD in the 3 distraction groups was significantly lower than that in control group (p <  0.05). Several items of profile of mood states (POMS) and the impression of EGD at post-distraction improved significantly compared to those at pre-distraction among the 3 distraction groups (p <  0.05). Visual analog scale (VAS) of willingness for the next use of distraction in the 3 distraction groups was excellent because VAS was more than 70. CONCLUSIONS: Distractions effectively improved psychological factors, vital signs and some of HRV at pre and post-EGD. Distractions may suppress BP elevation during the latter half of EGD and lead to stability of HRV on EGD. TRIAL REGISTRATION: This prospective trial was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000029637. Registered on 20 October 2017.

[A Case of Colorectal Cancer with Peritoneal Dissemination and Liver Metastasis That Responded to Comprehensive Treatment by Chemotherapy and CRS plus HIPEC].

We report a case of colorectal cancer with peritoneal dissemination and liver metastasis that achieved R0 resection by preoperative chemotherapy and CRS plus HIPEC. A 33-year-old man presented with a complaint of abdominal bloating. After further examination, he was diagnosed with transverse colon cancer with peritoneal dissemination and liver metastasis. After 9 courses of preoperative XELOX plus cetuximab and 4 courses of preoperative XELIRI plus bevacizumab, he underwent transverse colon resection, peritoneal resection, and HIPEC(MMC 20mg/4,000mL physiological saline, 40mins). There was little histological evidence of peritoneal dissemination around the region of the primary tumor. Moreover, no tumor cells were found in other peritoneal disseminations or in the liver metastasis. As a result, he was able to undergo curative resection. Colorectal cancer with peritoneal dissemination still has a poor prognosis, but combination therapy with chemotherapy and CRS plus HIPEC is expected to improve prognosis.

Preparation of Orally Disintegrating Tablets Containing Powdered Tea Leaves with Enriched Levels of Bioactive Compounds by Means of Microwave Irradiation Technique.

In the present study, a microwave treatment process has been applied to prepare orally disintegrating tablets (ODTs) containing powdered tea leaves with enriched levels of the anti-inflammatory compounds such as chafuroside A (CFA) and chafuroside B (CFB). The use of distilled water as the adsorbed and granulation solvents in this preparation process afforded tablets with a long disintegration time (more than 120 s). The CFA and CFB contents of these tablets did not also change after 4 min of microwave irradiation due to the tablet temperature, which only increased to 100°C. In contrast, the tablet temperature increased up to 140°C after 3 min of microwave irradiation when a 1.68 M Na2HPO4 solution instead of distilled water. Notably, the disintegration time of these tablets was considerably improved (less than 20 s) compared with the microwave-untreated tablets, and there were 7- and 11-fold increases in their CFA and CFB contents. In addition, the operational conditions for the preparation of the tablets were optimized by face-centered composite design based on the following criteria: tablet hardness greater than 13 N, disintegration time less than 30 s and friability less than 0.5%. The requirements translated into X1 (the amount of granulation solvent), X2 (tableting pressure) and X3 (content of the powdered tea leaves) values of 45%, 0.43 kN and 32%, respectively, and the ODTs containing powdered tea leaves prepared under these optimized conditions were found to show excellent tablet properties and contain enriched levels of CFA and CFB.

Two randomized controlled studies comparing the nutritional benefits of branched-chain amino acid (BCAA) granules and a BCAA-enriched nutrient mixture for patients with esophageal varices after endoscopic treatment.

BACKGROUND: The usefulness of branched-chain amino acid (BCAA) granules and BCAA-enriched nutrient mixtures for patients with liver cirrhosis is often reported. However, no randomized controlled studies have investigated the usefulness of these supplements in the nutritional intervention of cirrhotic patients receiving endoscopic treatment for esophageal varices. METHODS: Patients without BCAA before endoscopic treatment were divided into study 1, and those who received BCAA were divided into study 2. In study 1, 44 eligible patients were divided into a control group (n = 13), a general liquid nutrient (snack) group (n = 15), and a BCAA-enriched nutrient mixture (BCAA-EN) group (n = 16). In study 2, 48 eligible patients were divided into a BCAA group (n = 24) and a BCAA-EN group (n = 24). The nutritional status including non-protein respiratory quotient (NPRQ) levels, weight gain, and albumin were evaluated on days 0, 7, and 50. RESULTS: In study 1, the BCAA-EN group showed significant improvement in NPRQ levels on day 7 as compared with the snack group. In study 2, the BCAA-EN group showed significant improvement in NPRQ levels on day 7 and in weight levels on day 50 relative to the BCAA group, while the BCAA group showed improved serum albumin levels on day 7 compared to the BCAA-EN group. CONCLUSIONS: The BCAA-enriched nutrient mixture maintained NPRQ and weight in cirrhotic patients. Our findings suggest that supplements including both BCAA and a nutritional energy supplement would be beneficial for cirrhotic patients undergoing endoscopic treatment for esophageal varices.

Photothermal ablation of tumor cells using a single-walled carbon nanotube-peptide composite.

Single-walled carbon nanotubes (SWCNTs) are known to have great potential for biomedical applications such as photothermal ablation of tumor cells in combination with near-infrared (NIR) irradiation. In this study, the photothermal activity of a novel SWCNTs composite with a designed peptide having a repeated structure of H-(-Lys-Phe-Lys-Ala-)7-OH [(KFKA)7] against tumor cells was evaluated in vitro and in vivo. The SWCNT-(KFKA)7 composite demonstrated high aqueous dispersibility that enabled SWCNTs to be used in tumor ablation. The NIR irradiation of SWCNT-(KFKA)7 solution resulted in a rapid temperature increase dependent on the SWCNTs concentration up to 50µg/ml. Three minutes of NIR irradiation of a colon 26 or HepG2 cell culture incubated with SWCNT-(KFKA)7 resulted in remarkable cell damage, while that by single treatment with SWCNT-(KFKA)7 or NIR irradiation alone was moderate. The intratumoral injection of SWCNT-(KFKA)7 solution followed by NIR irradiation resulted in a rapid increase of the temperature to 43°C in the subcutaneously inoculated colon 26 tumor based on thermographic observation and remarkable suppression of tumor growth compared with treatment with only SWCNT-(KFKA)7 injection alone or NIR irradiation alone. These results suggest the a great potential of an SWCNT-peptide composite for use in photothermal cancer therapy.