Changes in clinical outcomes in Japanese patients with hepatocellular carcinoma due to hepatitis C virus following the development of direct-acting antiviral agents.

BACKGROUND AND AIM: Direct-acting antivirals (DAAs) have been accessible in Japan since 2014. The aim of this study is to compare how the prognosis of patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCV-HCC) changed before and after DAA development. METHODS: A retrospective analysis of 1949 Japanese HCV-HCC patients from January 2000 to January 2023 categorized them into pre-DAA (before 2013, n = 1169) and post-DAA (after 2014, n = 780) groups. Changes in clinical features and prognosis were assessed. RESULTS: Despite no significant differences in BCLC stage between groups, the post-DAA group exhibited higher rates of sustained virological response (SVR) (45.6% vs. 9.8%), older age (73 vs 69 years), lower levels of AST (40 vs 56 IU/L), ALT (31 vs 46 IU/L), and AFP (11.7 vs 23.6 ng/mL), higher platelet count (13.5 vs 10.8 × 104/µL), better prothrombin time (88.0% vs 81.9%), and better ALBI score (-2.54 vs -2.36) (all P < 0.001). The post-DAA group also showed higher rates of curative treatments (74.1% vs 65.2%) and significantly improved recurrence-free survival (median 2.8 vs 2.1 years). Adjusted for inverse probability weighting, overall survival was superior in the post-DAA group (median 7.4 vs 5.6 years, P < 0.001). Subanalysis within the post-DAA group revealed significantly shorter overall survival for patients without SVR (median 4.8 years vs NA vs NA) compared to pre-SVR or post-SVR patients (both P < 0.001). No significant difference in OS was observed between the pre-SVR and post-SVR groups (P = 1.0). CONCLUSION: The development of DAA therapy has dramatically improved the prognosis of HCV-HCC patients.

Comparative analysis of the therapeutic outcomes of atezolizumab plus bevacizumab and lenvatinib for hepatocellular carcinoma patients aged 80 years and older: Multicenter study.

AIM: Elderly patients are believed to have a reduced immune capacity, which may make immunotherapy less effective. The aim of this study was to compare the therapeutic outcome of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) for advanced hepatocellular carcinoma (HCC) in patients aged 80 years and older. METHODS: From March 2018 to July 2022, 170 and 92 elderly patients who received LEN and Atez/Bev as first-line treatment, respectively, were retrospectively analyzed. RESULTS: The median ages of the Atez/Bev and LEN groups were 83.0 (8.01-86.0) and 83.0 (82.0-86.0) years (p = 0.3), respectively. Men accounted for approximately 70% of the patients in both groups. The objective response rate was 35.9% in the LEN group and 33.7% in the Atez/Bev group (p = 0.8), whereas the disease control rates in the LEN and Atez/Bev groups were 62.9% and 63.0%, respectively (p = 1.0). The median progression-free survival (PFS) in the LEN and Atez/Bev groups was 6.3 and 7.2 months, respectively, which were not significantly different (p = 0.2). The median overall survival (OS) was 17.9 months in the LEN group and 14.0 months in the Atez/Bev group. This difference was not statistically significant (p = 0.7). In multivariate analyses, the choice of treatment (LEN vs. Atez/Bev) showed no association with PFS or OS. The Atez/Bev group had a significantly higher rate of postprogression treatment (59.0% vs. 35.7%, p = 0.01) and a lower rate of discontinuation due to adverse events (69 [40.6%] vs. 19 [20.7%], p < 0.001) compared to the LEN group. CONCLUSIONS: Atezolizumab plus bevacizumab showed comparable effectiveness to LEN in HCC patients aged 80 years and older. Given the results of postprogression treatment and discontinuation due to adverse events, Atez/Bev could serve as a first-line treatment even for elderly HCC patients.

Comparing the impact of atezolizumab plus bevacizumab and lenvatinib on the liver function in hepatocellular carcinoma patients: A mixed-effects regression model approach.

AIM: This retrospective study compared the impact of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) on the liver function in patients with hepatocellular carcinoma. METHODS: We included 526 patients who received Atez/Bev and 731 who received LEN March 2018 and July 2022 in this study. We conducted a 1:1 propensity-score-matched analysis and identified 324 patients in each group for inclusion in the present analysis. Nonlinear mixed-effects regression models were employed, allowing for the evaluation and inclusion of cases where treatment was interrupted due to disease progression, adverse events, or loss to follow-up. These models were used to compare the ALBI score between the Atez/Bev and LEN groups. RESULTS: Following propensity score matching, the mean ALBI scores in the Atez/Bev and LEN groups were -2.41 ± 0.40 and -2.44 ± 0.42 at baseline, and -2.17 ± 0.56 and -2.19 ± 0.58 at 12 weeks, respectively. Although the ALBI score significantly worsened during treatment in both groups (p < 0.001), there was no significant difference in the rate of ALBI score deterioration between the groups (p = 0.06). Subgroup analyses showed that LEN-treated patients with BCLC advanced stage (p = 0.02) and those who initially received the full dose (p < 0.001) had a significantly greater worsening of ALBI score compared to Atez/Bev. CONCLUSIONS: Using a nonlinear mixed-effects regression approach, which allowed for the inclusion of cases with treatment interruption, we found no significant difference in the trend of liver function deterioration between the Atez/Bev and LEN groups. Caution should be exercised for LEN-treated patients with BCLC advanced stage or those receiving the full dose of LEN.

Usefulness of Tumor Marker Score for Predicting the Prognosis of Hepatocellular Carcinoma Patients Treated with Atezolizumab Plus Bevacizumab: A Multicenter Retrospective Study.

AIM: This study aimed to evaluate the ability of a previously reported tumor marker (TM) score involving alpha-fetoprotein (AFP), fucosylated AFP (AFP-L3), and des gamma-carboxy prothrombin (DCP) as TMs in predicting the prognosis and therapeutic efficacy in hepatocellular carcinoma (HCC) patients administered atezolizumab plus bevacizumab (Atez/Bev) as first-line treatment. MATERIALS/METHODS: The study period covered September 2020 to December 2022 and involved 371 HCC patients treated with Atez/Bev. The values of the TMs AFP, AFP-L3, and DCP were measured upon introducing Atez/Bev. Elevations in the values of AFP (≥100 ng/mL), AFP-L3 (≥10%), and DCP (≥100 mAU/mL) were considered to indicate a positive TM. The number of positive TMs was summed up and used as the TM score, as previously proposed. Hepatic reserve function was assessed using the modified albumin-bilirubin grade (mALBI). Predictive values for prognosis were evaluated retrospectively. RESULTS: A TM score of 0 was shown in 81 HCC patients (21.8%), 1 in 110 (29.6%), 2 in 112 (29.9%), and 3 in 68 (18.3%). The median overall survival (OS) times for TM scores 0, 1, 2, and 3 were not applicable [NA] (95% CI NA-NA), 24.0 months (95% CI 17.8-NA), 16.7 months (95% CI 17.8-NA), and NA (95% CI 8.3-NA), respectively (p < 0.001). The median progression-free survival (PFS) times for TM scores 0, 1, 2, and 3 were 16.5 months (95% CI 8.0-not applicable [NA]), 13.8 months (95% CI 10.6-21.3), 7.7 months (95% CI 5.3-8.9), and 5.8 months (95% CI 3.0-7.6), respectively (p < 0.001). OS was well stratified in mALBI 1/2a and mALBI 2a/2b. PFS was well stratified in mALBI 2a/2b, but not in mALBI 1/2a. CONCLUSIONS: The TM score involving AFP, AFP-L3, and DCP as TMs was useful in predicting the prognosis and therapeutic efficacy in terms of OS and PFS in HCC patients administered Atez/Bev as first-line treatment.

Oral Administration of Chaetoceros gracilis-A Marine Microalga-Alleviates Hepatic Lipid Accumulation in Rats Fed a High-Sucrose and Cholesterol-Containing Diet.

Microalgae are attracting attention as a next-generation alternative source of protein and essential fatty acids that do not consume large amounts of water or land. Chaetoceros gracilis (C. gracilis)-a marine microalga-is rich in proteins, fucoxanthin, and eicosapentaenoic acid (EPA). Growing evidence indicates that dietary fucoxanthin and EPA have beneficial effects in humans. However, none of these studies have shown that dietary C. gracilis has beneficial effects in mammals. In this study, we investigated the effects of dietary C. gracilis on lipid abnormalities in Sprague-Dawley rats fed a high-sucrose cholesterol-containing diet. Dried C. gracilis was added to the control diet at a final dose of 2 or 5% (w/w). After four weeks, the soleus muscle weights were found to be dose-responsive to C. gracilis and showed a tendency to increase. The hepatic triglyceride and total cholesterol levels were significantly reduced by C. gracilis feeding compared to those in the control group. The activities of FAS and G6PDH, which are related to fatty acid de novo synthesis, were found to be dose-responsive to C. gracilis and tended to decrease. The hepatic glycerol content was also significantly decreased by C. gracilis feeding, and the serum HDL cholesterol levels were significantly increased, whereas the serum levels of cholesterol absorption markers (i.e., campesterol and ß-sitosterol) and the hepatic mRNA levels of Scarb1 were significantly decreased. Water-soluble metabolite analysis showed that the muscular contents of several amino acids, including leucine, were significantly increased by C. gracilis feeding. The tendency toward an increase in the weight of the soleus muscle as a result of C. gracilis feeding may be due to the enhancement of muscle protein synthesis centered on leucine. Collectively, these results show that the oral administration of C. gracilis alleviates hepatic lipid accumulation in rats fed a high-sucrose and cholesterol-containing diet, indicating the potential use of C. gracilis as a food resource.

Re-intervention with 10-mm vs 12-mm covered self-expandable metallic stent for recurrent unresectable distal biliary obstruction in patients with previous stent implantation.

BACKGROUND: Treatment for unresectable distal malignant biliary obstruction (DMBO) involves placing a 10-mm covered self-expandable metallic stent (CSEMS). In recurrent biliary obstruction (RBO), replacement of the CSEMS is recommended; however, the appropriate stent type remains unknown. We speculated that large-bore CSEMSs would provide longer patency. We compared the efficacy of 10-mm and 12-mm CSEMS in patients with RBO. METHODS: We retrospectively retrieved data on patients who underwent CSEMS replacement from the endoscopic database. We investigated the time to RBO (TRBO) after CSEMS replacement. The hazard ratio (HR) for the the second TRBO was estimated using the Cox proportional hazard model. The estimated median second TRBO was determined using the Kaplan-Meier method. RESULTS: Among the 493 patients with DMBOs treated with 10-mm CSEMS, 48 and 29 patients underwent re-intervention with 10-mm and 12-mm CSEMS, respectively. The use of 12-mm CSEMS was inversely associated with second TRBO (multivariable-adjusted HR, 0.62; 95% CI, 0.39-0.98; P = .042). The estimated median second TRBO was greater with the 12 mm CSEMS than with the 10 mm variety (562 days vs 207 days; P = .019). CONCLUSION: The second intervention with 12-mm CSEMS was associated with a longer TRBO.

Comparing the Efficacy and Safety of Gemcitabine plus Nab-Paclitaxel versus Gemcitabine Alone in Older Adults with Unresectable Pancreatic Cancer.

BACKGROUND: Gemcitabine plus nab-paclitaxel (GnP) has been a standard treatment for unresectable pancreatic cancer (uPC); however, the current treatment status and usefulness in older adults with uPC remain unclear. Therefore, we aimed to investigate the patient background and compare the efficacy and safety of GnP versus other treatments in older adults with uPC. PATIENTS AND METHODS: In this prospective observational study, we enrolled 233 eligible patients aged ≥76 years with pathologically proven, clinically uPC, and no history of chemotherapy from 55 Japanese centers during September 2018-September 2019. The main endpoints were overall survival (OS), progression-free survival (PFS), and safety. Geriatric assessments were performed upon registration and after 3 months. To adjust for confounders, we conducted propensity score-matched analyses. RESULTS: GnP, gemcitabine alone (Gem), best supportive care, and other therapies were administered to 116, 72, 16, and 29 patients, respectively. In the propensity score-matched analysis, 42 patients each were selected from the GnP and Gem groups. The median OS was longer in the GnP group than in the Gem group (12.2 vs. 9.4 months; hazard ratio [HR], 0.65; 95% CI, 0.37-1.13). The median PFS was significantly longer in the GnP group than in the Gem group (9.2 vs. 3.7 months; HR, 0.38; 95% CI, 0.23-0.64). The incidence of severe adverse events was higher with GnP than with Gem; however, the difference was not significant. CONCLUSION: GnP is more efficacious than Gem in patients aged ≥76 years with uPC despite demonstrating a higher incidence of severe adverse events.

Potential of PALBI-T score as a prognostic model for hepatocellular carcinoma in alcoholic liver disease.

BACKGROUND AND AIM: With the control of viral hepatitis, alcoholic hepatocellular carcinoma (HCC) is becoming increasingly important in Japan. In alcoholic cirrhosis, the impact of portal hypertension is significant. Thus, it may be difficult to predict prognosis accurately with the reported prognostic scores. Here we propose the platelet-albumin-bilirubin tumor nodes metastasis (TNM) score (PALBI-T score) as a prognostic model for HCC in alcoholic liver disease, and investigate its usefulness. The PALBI-T score is an integrated score based on the TNM stage and PALBI grade including platelets, reflecting portal hypertension. METHODS: This study included 163 patients with alcoholic HCC treated at our Center from 1997 to 2018. We compared the prognostic prediction abilities of the Japan Integrated Staging (JIS) score, ALBI-T score, and PALBI-T score. The PALBI-T score was calculated similarly to the JIS and ALBI-T scores. Areas under the receiver operating characteristic curve (AUC) were calculated for predicting overall survival (OS). RESULTS: In predicting the 1-year survival, the JIS score had a larger AUC (AUC = 0.925) than the ALBI-T score (AUC = 0.895) and PALBI-T score (AUC = 0.891). On the other hand, there was no significant difference in predicting OS among the integrated scores. The PALBI-T score (AUC = 0.740) had the largest AUC, and the JIS score (AUC = 0.729) and ALBI-T score (AUC = 0.717) were not significantly different from the PALBI grade (AUC = 0.634). The PALBI grade reflected the degree of portal hypertension. CONCLUSION: In patients with alcoholic HCC, the Japan Integrated Staging score is useful for predicting short-term prognosis. The PALBI-T score, which reflects portal hypertension, appears to be a more valid prognostic score for predicting long-term prognosis.

Environmental factors, medical and family history, and comorbidities associated with primary biliary cholangitis in Japan: a multicenter case-control study.

BACKGROUND: Primary biliary cholangitis (PBC) is considered to be caused by the interaction between genetic background and environmental triggers. Previous case-control studies have indicated the associations of environmental factors (tobacco smoking, a history of urinary tract infection, and hair dye) use with PBC. Therefore, we conducted a multicenter case-control study to identify the environmental factors associated with the development of PBC in Japan. METHODS: From 21 participating centers in Japan, we prospectively enrolled 548 patients with PBC (male/female = 78/470, median age 66), and 548 age- and sex-matched controls. These participants completed a questionnaire comprising 121 items with respect to demographic, anthropometric, socioeconomic features, lifestyle, medical/familial history, and reproductive history in female individuals. The association was determined using conditional multivariate logistic regression analysis. RESULTS: The identified factors were vault toilet at home in childhood [odds ratio (OR), 1.63; 95% confidence interval (CI), 1.01-2.62], unpaved roads around the house in childhood (OR, 1.43; 95% CI, 1.07-1.92), ever smoking (OR, 1.70; 95% CI, 1.28-2.25), and hair dye use (OR, 1.57; 95% CI, 1.15-2.14) in the model for lifestyle factors, and a history of any type of autoimmune disease (OR, 8.74; 95% CI, 3.99-19.13), a history of Cesarean section (OR, 0.20; 95% CI, 0.077-0.53), and presence of PBC in first-degree relatives (OR, 21.1; 95% CI, 6.52-68.0) in the model for medical and familial factors. CONCLUSIONS: These results suggest that poor environmental hygiene in childhood (vault toilets and unpaved roads) and chronic exposure to chemicals (smoking and hair dye use) are likely to be risk factors for the development of PBC in Japan.

Role of endoscopic ultrasound for gallbladder disease.

Endoscopic ultrasonography (EUS) has excellent spatial resolution and allows more detailed examination than abdominal ultrasonography (US) in terms of qualitative diagnosis of tumors and evaluation of tumor invasion depth. To understand the role of EUS in gallbladder disease, we need to understand the normal gallbladder wall structure and how to visualize it on EUS. In addition, gallbladder lesions can be classified into two broad categories: protuberant and wall-thickening lesions. Here, the features on EUS were outlined. We also outlined the current status of EUS-FNA for gallbladder lesions as there have been scattered reports of EUS-FNA in recent years.

Correction to: Very long chain fatty acids are an important marker of nutritional status in patients with anorexia nervosa: a case control study.

[This corrects the article DOI: 10.1186/s13030-020-00186-8.].

Very long chain fatty acids are an important marker of nutritional status in patients with anorexia nervosa: a case control study.

BACKGROUND: Anorexia nervosa (AN) is a disease resulting in extreme weight loss. It is caused by multiple factors, including psychosocial, environmental, and genetic factors. A genetic abnormality affecting lipid metabolism has been recently reported in patients with AN. However, it is unknown whether lipid metabolism abnormalities in AN are caused by eating behavior, undernutrition, and/or genetic factors. The meaning of lipid metabolism in AN remains unclear. In particular, differences in the profiles of very long-chain fatty acids (VLCFAs) in patients with various types of AN have not been studied. This study aimed to determine changes to the fatty acid profile over a 3-month period, specifically that of long-chain fatty acids (LCFAs) and VLCFAs in patients with various types of AN. METHODS: We evaluated 69 female patients with AN, subclassified as AN-restricting type (AN-R) and AN-Binge-Eating/Purging type (AN-BP). On admission and after 3 months of treatment, height, weight, body mass index, plasma and serum parameters, and plasma fatty acid concentrations were measured in all patients. The control group included 25 healthy, age-matched women. Comparisons between the groups were made using one-way ANOVA, while those between the various parameters at admission and after 3 months within each group were made using the Wilcoxon signed rank test. RESULTS: On admission, the AN-R and the AN-BP groups had significantly higher levels of 18-24C and > 14C fatty acids (LCFAs and VLCFAs, respectively) than the control group. After 3 months of treatment, both groups showed high levels of 14-24C fatty acids. The levels of VLCFAs (C22:0 and C24:0) and LCFA (C18:3) after 3 months of treatment remained high in both AN groups relative to the control group. CONCLUSIONS: Eating behaviors appear to be associated with levels of LCFAs. Lipid metabolism abnormalities under conditions of starvation in AN might have a genetic basis and appear to be associated with VLCFA (C22:0 and C24:0) and LCFA (C18:3) levels.

Endoscopic ultrasound-guided fine needle aspiration for diagnosing pancreatic mass in patients with surgically altered upper gastrointestinal anatomy.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has been established as a safe and accurate method for diagnosing a pancreatic mass; however, EUS-FNA for patients with surgically altered upper gastrointestinal (UGI) anatomy has not yet been investigated sufficiently. Therefore, the feasibility and safety of EUS-FNA in these patients were retrospectively investigated. METHODS: Patients in whom EUS-FNA was performed between March 2008 and April 2017 were retrospectively investigated in terms of EUS-FNA technical success, procedure time, diagnostic accuracies of cytology and histology, and procedure-related adverse events. RESULTS: Twenty-five EUS-FNAs were performed for 15 pancreatic body-to-tail and 10 head lesions. All patients underwent EUS-FNA successfully; however, changing of the echoendoscope to a forward-viewing echoendoscope and preplacement of a nasobiliary catheter by balloon-assisted enteroscopy for guidance were needed in one and two cases, respectively. The median procedure time was 26 min (range, 16-70). The diagnostic accuracies were 76%, 84%, and 88% for cytology, histology, and combined use, respectively. Adverse events were not observed. CONCLUSIONS: Endoscopic ultrasound-guided FNA is a safe and efficient method for diagnosing a pancreatic mass even in patients with surgically altered UGI anatomy. Nevertheless, some sophisticated techniques are required for pancreatic head lesions if reaching the duodenum after passing through the jejunal limb is required for visualization of the pancreatic mass.

Dietary fat, cholesterol, and cholic acid affect the histopathologic severity of nonalcoholic steatohepatitis in Sprague-Dawley rats.

Understanding of the pathogenesis of nonalcoholic steatohepatitis (NASH)-associated fibrosis has been hampered by the lack of a comprehensive and physiological small animal model of NASH with fibrosis. Feeding a high-fat and high-cholesterol (HFC) diet supplemented with cholic acid to rats is known to replicate human NASH pathology, and it induces fibrosis earlier than with an HFC diet alone. In the present study, physiological and histopathological observations from 65 Sprague-Dawley (SD) rats fed an HFC diet with or without cholic acid for 9 or 18 weeks in our laboratory between January 2013 and February 2018 were retrospectively reviewed. The liver weight/body weight ratio at the end of the rearing period was higher in rats fed an HFC diet than in rats fed a normal diet in a cholesterol dose-, cholic acid dose-, or rearing period dependent manner. Dietary fat, cholesterol and/or cholic acid and rearing period affected the histopathologic severity of NASH. Overall, 56 (86.2%) of 65 SD rats fed an HFC diet for 9 or 18 weeks developed histopathologically proven NASH. It is noted that the SD rats fed an HFC diet supplemented with 2% (w/w) cholic acid for 18 weeks frequently developed advanced fibrosis, including cirrhosis. Thus, this diet-induced NASH rat model is likely to be a highly reproducible.

Absorption and Metabolic Behavior of Hesperidin (Rutinosylated Hesperetin) after Single Oral Administration to Sprague-Dawley Rats.

We investigated the absorption and metabolic behavior of hesperidin (hesperetin-7-O-rutinoside) in the blood system of Sprague-Dawley rats by liquid chromatography- and matrix-assisted laser desorption ionization mass spectrometries (LC-MS and MALDI-MS). After a single oral administration of hesperidin (10 mg/kg), which was expected to be absorbed in its degraded hesperetin form, we detected intact hesperidin in the portal vein blood (tmax, 2 h) for the first time. We successfully detected glucuronized hesperidin in the circulating bloodstream, while intact hesperidin had disappeared. Further MS analyses revealed that homoeriodictyol and eriodictyol conjugates were detected in both portal and circulating blood systems. This indicated that hesperidin and/or hesperetin are susceptible to methylation and demethylation during the intestinal membrane transport process. Sulfated and glucuronized metabolites were also detected in both blood systems. In conclusion, hesperidin can enter into the circulating bloodstream in its conjugated forms, together with the conjugated forms of hesperetin, homoeriodictyol, and/or eriodictyol.

Enteral self-expandable metal stent placement for malignant afferent limb syndrome using single-balloon enteroscope: report of five cases.

Endoscopic enteral self-expandable metal stent (SEMS) placement is a useful alternative treatment option for malignant afferent limb syndrome (ALS). We investigated the safety, efficacy, and follow-up results of enteral SEMS placement using a single-balloon enteroscope for the treatment of malignant ALS.

Dietary Sparassis crispa Reduces Body Fat Mass and Hepatic Lipid Levels by Enhancing Energy Expenditure and Suppressing Lipogenesis in Rats.

Accumulation of abdominal fat triggers metabolic syndrome, which is a cluster of metabolic abnormalities, such as dyslipidemia, glucose intolerance, insulin resistance or hyperinsulinemia, and hypertension, that leads to the development of diabetes and cardiovascular disease. Mushrooms have been used as a foodstuff and folk medicine worldwide. Among these mushrooms, Sparassis crispa (SC) is a relatively newly cultivated edible and medicinal mushroom, which has been reported to have anti-diabetic and anti-hypertensive properties. However, little is known about the anti-obesity and anti-hyperlipidemic properties of SC. In the present study, we investigated the effects of dietary SC on lipid metabolism and energy expenditure in Sprague-Dawley rats with diet-induced obesity and diabetes, and conducted respiratory gas analysis to determine how energy metabolism is altered by SC. After feeding periods of 3 and 7 weeks, dietary SC had significantly reduced hepatic triacylglycerol and cholesterol contents in a dose-dependent manner. These changes were attributable to suppression of fatty acid and cholesterol synthesis in the liver and increased insulin sensitivity in the body. In addition, after a feeding period of 6 weeks, dietary SC significantly increased energy expenditure through carbohydrate oxidation, reducing abdominal fat mass after 7 weeks. In conclusion, our results indicate that in addition to the previously reported anti-diabetic and anti-hypertensive activities, dietary SC exhibits anti-obesity and anti-hyperlipidemic activities that help protect against metabolic syndrome.

A fermented mixed tea made with camellia (Camellia japonica) and third-crop green tea leaves prevents nonalcoholic steatohepatitis in Sprague-Dawley rats fed a high-fat and high-cholesterol diet.

BACKGROUND: Established treatments for non-alcoholic steatohepatitis (NASH) are few, thus it is imperative to develop novel dietary strategies that can prevent NASH. A fermented mixed tea (FMT) made with Camellia japonica (Japanese camellia) and third- crop green tea leaves by tea-rolling processing was reported to reduce body weight and adipose tissue weight in Sprague-Dawley (SD) rats. Because visceral fat is one of the most important factors for the development of hepatic steatosis, this FMT supplementation can be a candidate dietary strategy for the prevention of NASH. METHODS: Nine-week-old male SD rats were fed a high-fat and high-cholesterol (HFC) diets with or without FMT (camellia and third-crop green tea leaves at ratios of 1:5, 1:2 and 1:1) for 9 weeks (n=6-7/group). Histopathology, serology and expressions of fibrogenetic, proinflammatory, oxidative stress and lipid metabolism-related genes in the liver were evaluated. RESULTS: Histologically, HFC diet with FMT at a ratio of 1:5 dramatically reduced NASH progression (14%) compared to the HFC diet without FMT (100%). FMT at a ratio of 1:5 reduced hepatic steatosis due to the activation of microsomal triglyceride transfer protein, and FMT at a ratio of 1:2 reduced mRNA levels of some proinflammatory, lipid metabolism-related, fibrogenic and oxidative stress marker genes. CONCLUSIONS: Our data suggest that FMT at a ratio of 1:5 or 1:2 likely possesses a preventive effect on NASH progression.

Rare sugars, d-allulose, d-tagatose and d-sorbose, differently modulate lipid metabolism in rats.

BACKGROUND: Rare sugars including d-allulose, d-tagatose, and d-sorbose are present in limited quantities in nature; some of these rare sugars are now commercially produced using microbial enzymes. Apart from the anti-obesity and anti-hyperglycaemic activities of d-allulose, effects of these sugars on lipid metabolism have not been investigated. Therefore, we aimed to determine if and how d-tagatose and d-sorbose modulate lipid metabolism in rats. After feeding these rare sugars to rats, parameters on lipid metabolism were determined. RESULTS: No diet-related effects were observed on body weight and food intake. Hepatic lipogenic enzyme activity was lowered by d-allulose and d-sorbose but increased by d-tagatose. Faecal fatty acid excretion was non-significantly decreased by d-allulose, but significantly increased by d-sorbose without affecting faecal steroid excretion. A trend toward reduced adipose tissue weight was observed in groups fed rare sugars. Serum adiponectin levels were decreased by d-sorbose relative to the control. Gene expression of cholesterol metabolism-related liver proteins tended to be down-regulated by d-allulose and d-sorbose but not by d-tagatose. In the small intestine, SR-B1 mRNA expression was suppressed by d-sorbose. CONCLUSION: Lipid metabolism in rats varies with rare sugars. Application of rare sugars to functional foods for healthy body weight maintenance requires further studies. © 2017 Society of Chemical Industry.

Effect of Controlled Ice Nucleation on Stability of Lactate Dehydrogenase During Freeze-Drying.

Several controlled ice nucleation techniques have been developed to increase the efficiency of the freeze-drying process as well as to improve the quality of pharmaceutical products. Owing to the reduction in ice surface area, these techniques have the potential to reduce the degradation of proteins labile during freezing. The objective of this study was to evaluate the effect of ice nucleation temperature on the in-process stability of lactate dehydrogenase (LDH). LDH in potassium phosphate buffer was nucleated at -4°C, -8°C, and -12°C using ControLyo™ or allowed to nucleate spontaneously. Both the enzymatic activity and tetramer recovery after freeze-thawing linearly correlated with product ice nucleation temperature (n = 24). Controlled nucleation also significantly improved batch homogeneity as reflected by reduced inter-vial variation in activity and tetramer recovery. With the correlation established in the laboratory, the degradation of protein in manufacturing arising from ice nucleation temperature differences can be quantitatively predicted. The results show that controlled nucleation reduced the degradation of LDH during the freezing process, but this does not necessarily translate to vastly superior stability during the entire freeze-drying process. The capability of improving batch homogeneity provides potential advantages in scaling-up from lab to manufacturing scale.