Essential trace element and phosphatidylcholine remodeling: Implications for body composition and insulin resistance.

BACKGROUND: Recent studies indicated that bioactive lipids of phosphatidylcholines (PCs) and lysophosphatidylcholines (LysoPCs) predict unhealthy metabolic phenotypes, but results remain inconsistent. To fill this knowledge gap, we investigated whether essential trace elements affect PC-Lyso PC remodeling pathways and the risk of insulin resistance (IR). METHODS: Anthropometric and blood biochemical data (glucose, insulin, and lipoprotein-associated phospholipase A2 (Lp-PLA2)) were obtained from 99 adults. Blood essential/probably essential trace elements and lipid metabolites were respectively measured by inductively coupled plasma mass spectrometry (ICP-MS), and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). RESULT AND CONCLUSION: Except for LysoPC (O-18:0/0:0), an inverse V shape was observed between body weight and PC and LysoPC species. A Pearson correlation analysis showed that essential/probably-essential metals (Se, Cu, and Ni: r=-0.4∼-0.7) were negatively correlated with PC metabolites but positively correlated with LysoPC (O-18:0/0:0) (Se, Cu, and Ni: r=0.85-0.64). Quantile-g computation showed that one quantile increase in essential metals was associated with a 2.16-fold increase in serum Lp-PLA2 (ß=2.16 (95 % confidence interval (CI): 0.34, 3.98), p=0.023), which are key enzymes involved in PC/Lyso PC metabolism. An interactive analysis showed that compared to those with the lowest levels (reference), individuals with the highest levels of serum PCs (pooled, M2) and the lowest essential/probably essential metals (M1) were associated with a healthier body composition and had a 76 % decreased risk of IR (odds ratio (OR)=0.24 (95 % CI: 0.06, 0.90), p<0.05). In contrast, increased exposure to LysoPC(O-18:0/0:0) (M2) and essential metals (M2) exhibited an 8.22-times highest risk of IR (OR= 8.22 (2.07, 32.57), p<0.05) as well as an altered body composition. In conclusion, overexposure to essential/probably essential trace elements may promote an unhealthy body weight and IR through modulating PC/LysoPC remodeling pathways.

Modified enhanced recovery after surgery protocol in octogenarians undergoing minimally invasive colorectal cancer surgery.

BACKGROUND: Colorectal cancer (CRC) is a major health issue worldwide. As the population ages, more older patients including octogenarians will require CRC treatment. However, this vulnerable group has decreased functional reserves and increased surgical risks. Enhanced recovery after surgery (ERAS) pathways aim to reduce surgical stress and complications, but concerns remain about applying ERAS protocols to older patients. We assessed whether a modified ERAS (mERAS) protocol combined would improve outcomes in octogenarian CRC patients undergoing minimally invasive surgery. METHODS: In this retrospective cohort study, we compared 360 non-octogenarians aged 50-64 years and 114 octogenarians aged 80-89 years before and after mERAS protocol implementation. Outcomes including postoperative functionary recovery, length of stay, complications, emergency department visits, and readmissions were analyzed. RESULTS: Despite comparable tumor characteristics, octogenarians had poorer nutrition, American Society of Anesthesiologists status, and more comorbidities. After mERAS, octogenarians had reduced complications, faster return of bowel function, and shorter postoperative length of stay, similar to non-octogenarians. mERAS implementation improved recovery in both groups without increasing emergency department visits or readmissions. CONCLUSION: Although less remarkable than in non-octogenarians, mERAS protocols mitigated higher complication rates and improved recovery in octogenarians after minimally invasive surgery for CRC, confirming protocol feasibility and safety in this vulnerable population.

Therapeutic Effect of Human Adipocyte-derived Stem Cell-derived Exosomes on a Transgenic Mouse Model of Parkinson's Disease.

BACKGROUND/AIM: Stem cell therapy and regenerative medicine are promising for treating Parkinson's disease (PD) not only for the potential for cell replacement but also for the paracrine effect of stem cell secretion, especially proteins and nucleotide-enriched exosomes. This study investigated the neuroprotective effect of exosomes secreted from human adipocyte-derived stem cells (hADSCs) on PD. MATERIALS AND METHODS: hADSCs were isolated from the visceral fat tissue of individuals without PD who underwent bariatric surgery and were validated using surface markers and differentiation ability. Exosomes were isolated from the culture medium of hADSCs through serial ultracentrifugation and validated. Condensed exosomes were administered intravenously to 12-week-old MitoPark mice, transgenic parkinsonism mouse model with conditional knockout of mitochondrial transcription factor A in dopaminergic neurons, monthly for 3 months. Motor function, gait, and memory were assessed monthly, and immunohistochemical analysis of neuronal and inflammatory markers was performed at the end of the experiments. RESULTS: The hADSC-derived exosome-treated mice exhibited better motor function in beam walking and gait analyses than did the untreated mice. In the novel object recognition tests, the exosome-treated mice retained better memory function. Immunohistochemical analysis revealed that although exosome treatment did not prevent the loss of dopaminergic neurons in the substantia nigra of mice, it down-regulated microglial activation and neuroinflammation in the midbrain. CONCLUSION: hADSC-derived exosomes were neuroprotective in this in vivo mouse model of PD, likely because of their anti-inflammatory effect. Use of hADSC-derived exosomes may offer several beneficial effects in stem cell therapy. Since they can also be produced at an industrial level, they are a promising treatment option for PD and other neurodegenerative diseases.

Potential Hepatic Lipid Markers Associated with Nonalcoholic Steatohepatitis and Fibrosis in Morbid Obesity Patients.

This study investigated differences in lipidomic profile features in nonalcoholic steatohepatitis (NASH) between mild and significant liver fibrosis cases among patients with morbid obesity. Wedge liver biopsy was performed during sleeve gastrectomy and significant liver fibrosis was defined as a fibrosis score ≥ 2. We selected patients with NASH with non/mild fibrosis (stage F0-F1; n = 30) and NASH with significant fibrosis (stage F2-F4; n = 30). The results of the liver tissue lipidomic analysis revealed that the fold changes of triglyceride (TG) (52:6); cholesterol ester (CE) (20:1); phosphatidylcholine (PC) (38:0) and (50:8); phosphatidic acid (PA) (40:4); phosphatidylinositol (PI) (49:4); phosphatidylglycerol (PG) (40:2); and sphingomyelin (SM) (35:0) and (37:0) were significantly lower in patients with NASH with F2-F4 than those with NASH with F0-F1 (p < 0.05). However, the fold changes of PC (42:4) were relatively higher in patients with NASH with stage 2-4 fibrosis (p < 0.05). Moreover, predictive models incorporating serum markers levels, ultrasonographic studies, and levels of specific lipid components [PC (42:4) and PG (40:2)] yielded the highest area under receiver operating curve (0.941), suggesting a potential correlation between NASH fibrosis stages and liver lipid accumulation among specific lipid species subclasses. This study demonstrated that the concentrations of particular lipid species in the liver correlate with NASH fibrosis stages and may indicate hepatic steatosis regression or progression in patients with morbid obesity.

Prediction of 5-Year Weight Loss and Weight Regain According to Early Weight Loss after Sleeve Gastrectomy.

BACKGROUND: Patients with morbid obesity exhibit sustained weight loss after sleeve gastrectomy (SG), but some individuals exhibit subsequent weight regain in the following years. Early weight loss was proven as a predictor of short- and mid-term weight loss and regain. However, the long-term effects of early weight loss have yet to be fully investigated. This study investigated the predictive effects of early weight loss on long-term weight loss and regain after SG. METHODS: Data of patients who underwent SG from November 2011 to July 2016 and followed through July 2021 were collected retrospectively. Weight regain was defined by weight increase more than 25% of their lost weight at the first postoperative year. Linear regression analysis and Cox proportional hazards analysis were performed to evaluate the correlations among early weight loss, weight loss, and weight regain. RESULTS: Data of 408 patients were included. The percentages of total weight loss (%TWL) at postoperative months 1, 3, 12, and 60 were 10.6%, 18.1%, 29.3%, and 26.6%, respectively. The %TWL at months 1 and 3 were significantly correlated with %TWL after 5 years (P < .01). The weight regain rate was 29.8% at 5 years. The %TWL at months 1 and 3 significantly influenced weight regain (hazard ratio: 0.87 and 0.89, P = .017 and .008). CONCLUSION: Early weight loss may be used to predict weight loss and regain 5 years after SG. Patients with poor early weight loss are recommended to receive early interventions to achieve long-term weight loss and prevent weight regain.

Bariatric surgery trends and progress in Taiwan: 2010-2021.

INTRODUCTION: Taiwan is a leading country regarding bariatric surgery in Asia-Pacific. Since 2010, the Taiwan Society for Metabolic and Bariatric Surgery (TSMBS) has been accountable for the national evolution of bariatric surgery and inaugurated a national database accordingly. This study aimed to analyze the bariatric surgery trends and progress in Taiwan from 2010 to 2021. MATERIALS AND METHODS: The TSMBS database was collected on the basis of structured inquiries filled out by bariatric surgeons in Taiwan. All patients involving bariatric surgery were included. The data were stratified with the following objectives, including the types of bariatric procedures, demographic characteristics, and perioperative variables. A nationwide database was comprehensively analyzed and evaluated to determine the trends in the applications of the procedure. RESULTS: Data of 30,026 patients were enrolled. A 2.5-fold increase was observed in bariatric procedures, from 1218 in 2010 to 3005 in 2021. Within 12 years, female accounts for 61.8 %. The revisional rate was 3.40 % during the exploration stage (2010-2013), 2.77 % during the maturity stage (2013-2018), and 5.10 % during the expansion stage (2019-2021). The top five of primary bariatric surgery is sleeve gastrectomy (SG, 63.05 %), gastric clipping surgery (GC, 11.17 %), Roux-en-Y gastric bypass (RYGB, 9.34 %), one anastomosis gastric bypass (OAGB, 8.80 %), and sleeve plus surgery (SG plus, 4.43 %). CONCLUSION: The trends and progress of Taiwan's bariatric surgery within recent decades are presented in this article. Taiwan's bariatric surgery case number has increased steadily from 2010 to 2021. Amongst all, SG has become the most dominant procedure since 2011 while OAGB takes up second place in 2020.

Comparison of robotic reduced-port and laparoscopic approaches for left-sided colorectal cancer surgery.

BACKGROUND/OBJECTIVE: The reduced-port approach can overcome the limitations of single-incision laparoscopic surgery while maintaining its advantages. Here, we compared the effects of robotic reduced-port surgery and conventional laparoscopic approaches for left-sided colorectal cancer. METHODS: Between January 2015 and December 2016, the clinicopathological characteristics and treatment outcomes of 17 patients undergoing robotic reduced-port surgery and 49 patients undergoing laparoscopic surgery for left-sided colorectal cancer were compared. RESULTS: The two groups were comparable in almost all outcome measures except for the distal resection margin, which was significantly longer in the laparoscopic group (P < 0.001). The between-group differences in reoperation, incisional hernia development, and overall and progression-free survival were nonsignificant; however, the total hospital cost was significantly higher in the robotic group than in the laparoscopic group (US$13779.6 ± US$3114.8 vs. US$8556.3 ± US$2056.7, P < 0.001). CONCLUSION: Robotic reduced-port surgery for left-sided colorectal cancer is safe and effective but more expensive with no additional benefit compared with the conventional laparoscopic approach. This observation warrants further evaluation.

Haplotype of ESR1 and PPARD Genes Is Associated with Higher Anthropometric Changes in Han Chinese Obesity by Adjusting Dietary Factors-An 18-Month Follow-Up.

The obesity genetic effect may play a major role in obesogenic environment. A combined case-control and an 18-month follow-up were carried out, including a total of 311 controls and 118 obese cases. All participants were aged in the range of 20-55 y/o. The body mass index (BMI) of obese cases and normal controls was in the range of 27.0-34.9 and 18.5-23.9 kg/m2, respectively. The rs712221 on Estrogen receptor1 (ESR1) and rs2016520 on Peroxisome proliferator-activated receptor delta (PPARD) showed significant associations with obesity. The TT (odds ratio (OR): 2.42; 95% confidence interval (CI): 1.46-4.01) and TT/TC (OR: 2.80; 95% CI: 1.14-6.85) genotypes on rs712221 and rs2016520 had significantly higher obesity risks, respectively. Moreover, the synergic effect of these two risk SNPs (2-RGH) exhibited an almost geometrical increase in obesity risk (OR: 7.00; 95% CI: 2.23-21.99). Obese individuals with 2-RGH had apparently higher changes in BMI increase, body weight gain and dietary fiber intake but a lower total energy intake within the 18-month follow-up.

Efficacy and safety of one anastomosis gastric bypass versus Roux-en-Y gastric bypass for type 2 diabetes remission (ORDER): protocol of a multicentre, randomised controlled, open-label, superiority trial.

INTRODUCTION: Previous studies have demonstrated that one anastomosis gastric bypass (OAGB) is not inferior to Roux-en-Y gastric bypass (RYGB) in treating obesity. However, high level evidence comparing the efficacy and safety of both procedures in type 2 diabetes (T2D) treatment is still lacking, which is another main aim of bariatric surgery. The presented trial has been designed to aim at investigating the superiority of OAGB over the reference procedure RYGB in treating T2D as primary endpoint. And diabetes-related microvascular and macrovascular complications, cardiovascular comorbidities, weight loss, postoperative nutritional status, quality of life and overall complications will be followed up for 5 years as secondary endpoints. METHODS AND ANALYSIS: This prospective, multicentre, randomised superiority open-label trial will be conducted in patients of Asian descent. A total of 248 patients (BMI≥27.5 kg/m2) who are diagnosed with T2D will be randomly assigned (1:1) to OAGB or RYGB with blocks of four. The primary endpoint is the complete diabetes remission rate defined as HbA1c≤6.0% and fasting plasma glucose≤5.6 mmol/L without any antidiabetic medications at 1 year after surgery. All secondary endpoints will be measured at different follow-up visit points, which will start at least 3 months after enrolment, with a continuous annual follow-up for five postoperative years in order to provide solid evidence on the efficacy and safety of OAGB in patients with T2D. ETHICS AND DISSEMINATION: The study has been approved by the ethics committee of leading centre (Beijing Friendship Hospital, Capital Medical University, no. 2021-P2-037-03). The results generated from this work will be disseminated to academic audiences and the public via publications in international peer-reviewed journals and conferences. The data presented will be imported into a national data registry. Findings are expected to be available in 2025, which will facilitate clinical decision-making in the field. TRIAL REGISTRATION NUMBER: NCT05015283.

Evaluation of Persistent Efficacy of Diabetes Remission and Decline of Cardiovascular Risk After Laparoscopic Sleeve Gastrectomy: a Preliminary 1-Year Study.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a relative safe procedure in bariatric surgery. However, relatively few studies had been assessed its comprehensive efficacies. In the current study, the efficacies of LSG were comprehensively explored on glycemic control and cardiovascular disease (CVD) risk reduction. METHODS: A total of 95 obese patients, who owned body mass index (BMI) of more than 35, were recruited. All of them primarily underwent LSG from 2014 to 2016. Type 2 diabetes mellitus (T2DM) remission was defined as levels of glycated hemoglobin (A1C) and fasting blood glucose (FBG) of less than 6.4% and 125 mg/dL, respectively. The further efficacies of LSG on CVD and coronary heart disease (CHD) risks were explored by using original- and recalibrated Framingham 10-year CHD risk scores and the other 3 well-established CVD risk prediction models. RESULTS: Systolic blood pressure (SBP), serum FBG, A1C, triglyceride (TG), BMI, and body weight showed significantly declined and high-density lipoprotein-cholesterol (HDL) displayed twice higher than beginning level after LSG. The 71 of 95 patients with obesity were T2DM; 62 of them exhibited persistent DM remission until 1 year after LSG. Cardiovascular age, general cardiovascular risk (GCVR), and atherosclerotic cardiovascular disease risk (ASCVD) also showed significant decrements after LSG. We also observed significant reductions in estimated CVD and CHD risks. CONCLUSION: LSG resulted in a persistent T2DM remission and corrected metabolic abnormalities. Subsequently, LSG also benefits declined risks of CVD and 10-year CHD developments. LSG may be helpful for primary CVD care in obese patients with BMI of more than 35.

Ten Years of Change in Bariatric/Metabolic Surgery in the Asia-Pacific Region with COVID-19 Pandemic: IFSO-APC National Reports 2021.

BACKGROUND: On November 25, 2021, the IFSO-Asia-Pacific Chapter (IFSO-APC) Virtual Meeting 2021 was held online, and the representatives from the Asia-Pacific region presented 10 years of change in bariatric/metabolic surgery and the influence of COVID-19 in the special session of "IFSO-APC National Reports 2010-2020". We herein report the summarized data. METHODS: National bariatric/metabolic surgery data, which included the data of 2010 and 2020, were collected from the representatives using a questionnaire that consisted of 10 general questions. At the congress, the data were calculated and summarized. RESULTS: Thirteen of the 14 national societies responded to the survey. From 2010 to recent years, the populations of individuals with obesity (BMI ≥ 30 kg/m2) and individuals with diabetes both significantly increased. Eight countries and regions expanded the lower limit of criteria for bariatric surgery by 2-5 kg/m2 (BMI), and 5 countries newly established criteria for metabolic surgery in the last ten years. Sixty-nine percent of the countries currently run public health insurance systems, which doubled from 2010. The number of bariatric surgeons and institutions increased more than threefold from 2010. In 2010, 2019, and 2020, surgeons in IFSO-APC societies performed 18,280, 66,010, and 49,553 bariatric/metabolic surgeries, respectively. Due to the COVID pandemic, restriction policies significantly reduced access to surgery in South and Southeast Asian countries. The biggest changes included increased numbers of bariatric surgeons and institutions, operation numbers, public insurance coverage, raising awareness, and national registry systems. CONCLUSION: For the last 10 years, bariatric/metabolic surgery has rapidly grown in the Asia-Pacific region.

Fat-Free Mass and Skeletal Muscle Mass Gain Are Associated with Diabetes Remission after Laparoscopic Sleeve Gastrectomy in Males but Not in Females.

Besides massive body weight loss, laparoscopic sleeve gastrectomy (LSG) causes massive lean mass, including fat-free mass (FFM) and skeletal muscle mass (SM) that present higher metabolic rates in males. This study examines sex differences in FFM and SM changes of type 2 diabetes (T2D) remission at 12 months post-LSG. This cohort study recruited 119 patients (53.7% females) with T2D and obesity (body mass index 42.2 ± 7.0 kg/m2) who underwent LSG. Fat-mass (FM) loss was higher in males than in females (-12.8 ± 6.2% vs. -9.9 ± 5.0%, p = 0.02) after one-year post-operation. Regardless of the weight-loss difference, males had higher FFM and SM gain than did females (12.8 ± 8.0 vs. 9.9 ± 5.0% p = 0.02 and 6.5 ± 4.3% vs. 4.9 ± 6.2%, p = 0.03, respectively). Positive correlations of triglyceride reduction with FM loss (r = 0.47, p = 0.01) and SM gain (r = 0.44, p = 0.02) over 12 months post-operation were observed in males who achieved T2D remission. The T2D remission rate significantly increased 16% and 26% for each additional percentage of FFM and SM gain one year after LSG, which only happened in males. Increased FFM and SM were remarkably associated with T2D remission in males, but evidence lacks for females.

Predictors of diabetes relapse after metabolic surgery in Asia.

BACKGROUND: Limited studies have focused on diabetes relapse after metabolic surgery, especially among Asians. OBJECTIVES: To identify the predictors of diabetes relapse following initial postoperative remission in Asia. SETTING: Four tertiary hospitals METHODS: We assessed 342 patients (age, 41.0 ± 10.8 yr; body mass index [BMI], 39.6 ± 7.3 kg/m2) with complete diabetes data before and 1 and 3 years after metabolic surgery. A total of 290 (84.8%) and 277 (81.0%) patients had diabetes remission at 1 and 3 years after surgery. Logistic regressions were performed to identify the independent predictors of diabetes relapse. Two published predictive models for diabetes remission were also tested for relapse. RESULTS: Of the 290 patients with 1-year diabetes remission, 29 (10%) experienced a relapse at 3 years after surgery. The area under the receiver operating characteristic curve of the ABCD score in predicting 1-year remission, 3-year remission, and 3-year relapse were .814, .793, and .795, while those of the DiaRem2 score were .823, .774, and .701, respectively. The baseline age, BMI, and insulin use were independent predictors for relapse. The most powerful predictive model for relapse was composed of preoperative insulin use, 1-year A1C, and a change in BMI between the first and third year (C-statistic: .919). CONCLUSION: The ABCD score predicted both mid-term postoperative diabetes remission and relapse in Asians. Initial older age, lower BMI, insulin use, higher 1-year A1C, and weight regain were independent predictors of relapse. Personalized strategies should be proposed for those at risk of relapse to optimize diabetes outcomes after surgery.

Glucose-Regulated Protein 94 Mediates the Proliferation and Metastasis through the Regulation of ETV1 and MAPK Pathway in Colorectal Cancer.

Colorectal cancer (CRC) is a worldwide health problem. Glucose-regulated protein 94 (GRP94) is known as an important endoplasmic reticulum-stress response protein that shows correlation with aggressive cancer behavior. However, the role of GRP94 in CRC is still unclear. Our results showed that silencing GRP94 (GRP94-KD) reduced cell proliferation, invasion and migration of CRC cells and suppressed tumorigenesis in the xenograft mouse model. Rescue assay showed that ETV1 overexpression reversed the effect of GRP94 on cell proliferation and migration. In the molecular mechanism, we found that knockdown of GRP94 inhibited the level of MAPK pathway, including ERK/p-ERK, JNK/p-JNK, and p38/p-p38 signals. Cyclooxygenase-2 and epithelial-mesenchymal transformation biomarkers, such as N-cadherin, vimentin, and ß-catenin were suppressed in GRP94 knockdown cells. Treatment of specific inhibitors of MAPK pathway showed that ERK/p-ERK, and p38/p-p38 inhibitors significantly influenced ETV1 expression as compared to JNK/p-JNK inhibitor. Our results indicated that silencing GRP94 repressed the ability of EMT process, cancer cell proliferation, metastasis, and CRC tumorigenesis. Therefore, GRP94 may play an important role in CRC by regulating ETV1 and MAPK pathway.

Early weight loss as a predictor of 3-year weight loss and weight regain in patients with good compliance after sleeve gastrectomy.

BACKGROUND: Sleeve gastrectomy (SG) is the most common surgery for severe obesity. Patients lose weight post SG and regain some weight in the following years. Early weight loss predicts weight loss after SG. However, etiologies of weight loss and regain after SG remain unclear. OBJECTIVES: To investigate the effects of early weight loss on medium-term weight regain post SG. SETTING: Two university hospitals in Taiwan. METHODS: Patients with records within 1 and at 3 years after SG were enrolled retrospectively. Preoperative clinical variables and percentage of total weight loss (%TWL) were analyzed. Weight regain was defined as a weight increase from 1 year postoperatively of >25% of the lost weight. Linear and multiple logistic regression were applied to examine the associations of early weight loss, weight loss, and weight regain. RESULTS: A total of 363 patients were included. Body mass indexes before and 1, 3, 6, 12, and 36 months postoperatively were 40.7 ± 6.8 kg/m2, 36.6 ± 6.2 kg/m2, 33.5 ± 5.8 kg/m2, 30.9 ± 5.5 kg/m2, 28.4 ± 5.2, and 29.3 ± 5.4 kg/m2, respectively. At 3 years after SG, 73 patients (20.1%) had weight regain. In multivariate linear analyses, initial age, waist circumference, type 2 diabetes, and %TWL at 1 or 3 months were associated with either 1-year or 3-year %TWL. Multiple logistic regression revealed %TWL at 3 months to be a predictor for 3-year weight regain after SG (odds ratio, .927; P = .02). CONCLUSION: Early weight loss predicted weight loss and regain 3 years after SG. Early lifestyle and behavioral interventions are suggested in patients at high risk of poor weight loss and weight regain outcomes after SG.

Methyl gallate, gallic acid-derived compound, inhibit cell proliferation through increasing ROS production and apoptosis in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is a global health problem. Currently, there is no effective therapeutic strategy for HCC. Methyl gallate (MG), from plant-derived phenolic gallic acid, has exhibited antitumor efficacy. However, the effect of MG on HCC is unclear. In vitro growth activity was detected by a sulforhodamine assay. A zebrafish xenotransplantation was applied to evaluate the inhibitory effect of MG. Reactive oxygen species (ROS) production, autophagy, and lysosome formation were detected by specific dyes. Finally, apoptosis was examined using annexin V-FITC/PI staining and western blot was performed to determine the molecular mechanism. It was demonstrated that MG treatment inhibited the proliferation of Hep3B, Mahlavu, and HepJ5 cells. Xenotransplantation also showed that MG inhibited the growth of Hep3B and HepJ5 cells. MG treatment increased cellular levels of superoxide and oxidative stress. Increases in autophagy and lysosome formation were found after MG treatment. The western blot analysis showed that MG activated cleavage of caspase-3 and poly (SDP ribose) polymerase (PARP), modulated levels of the Bcl2, Bax, and Bad ligands, and induced apoptosis. MG induced autophagy with notable activation of beclin-1, autophagy related 5+12 (ATG5+12), and conversion of light chain 3-I (LC3-I) to II. Our study showed that MG exposure inhibited HCC proliferation both in vitro and in vivo. And blocking autophagy enhanced MG-induced cytotoxicity in HCC cells. These findings suggested MG might serve as a powerful therapeutic supplement for human HCC patients.

Efficacy of Different Procedures of Metabolic Surgery for Type 2 Diabetes in Asia: a Multinational and Multicenter Exploratory Study.

INTRODUCTION: Asian patients with diabetes exhibit different characteristics from Western patients. However, limited large-scale data are available on metabolic surgery procedures in Asia. We compared the short-term efficacies of metabolic surgery procedures for the management of Asian patients with different severities of diabetes. METHODS: We included patients undergoing metabolic surgery in five Asian institutions from January 2008 to December 2015 with at least 1-year postoperative follow-up. Outcomes of weight loss and diabetes control were determined. Diabetes remission rates in different ABCD scores and factors affecting diabetes remission were analyzed. RESULTS: A total of 1016 patients (mean BMI, 39.0 ± 7.2 kg/m2; HbA1c, 8.3% ± 1.7%) underwent metabolic surgery (197, Roux-en-Y gastric bypass [RYGB]; 171, one anastomosis gastric bypass [OAGB]; 437, sleeve gastrectomy [SG]; 130, SG with duodenal-jejunal bypass [SG-DJB]; and 81, single anastomosis duodenal-jejunal bypass with SG [SA-DJBSG]). The OAGB group exhibited significantly higher 1-year total weight loss (30.5%) and type 2 diabetes mellitus (T2DM) remission (78.4%) rates than did the other groups (p < .001). The patients with higher preoperative ABCD scores exhibited higher T2DM remission rates (81.8-100% and 9.5-46.2% in ABCD score subgroups of 9-10 and 1-2, respectively). In multivariate analysis, bypass was found to be an independent predictor of T2DM remission compared with SG (odds ratio of OAGB vs SG, 3.72; RYGB vs SG, 1.96; SG-DJB vs SG, 2.73; SA-DJBSG vs SG, 2.12). CONCLUSION: The metabolic surgeries are highly effective in T2DM treatment. However, SG may not be as effective as gastric bypass and duodenal-jejunum bypass.

One-pot fabrication of sacchachitin for production of TEMPO-oxidized sacchachitin nanofibers (TOSCNFs) utilized as scaffolds to enhance bone regeneration.

One-pot fabrication of sacchachitin (SC) for mass-production was developed and optimized by selecting KOH as alkaline agent in depigmentation step and utilizing NaClO2 as bleaching agent in subsequent step in the same pot. Overall yield of one-pot-fabricated SC was up to 35 %w/w of initial weight with a fibrous texture soft enough for mechanical disintegration into SC nanofibers (SCNFs) and better dispersion for producing TEMPO-oxidized SCNFs (T033SC). Both SCNFs and T033SC could form a 3D gelatinous scaffold into which MC3T3-E1 cells were attracted. Higher calcium-trapping ability of T033SC resulting from a greater extent of carboxylate groups provided an excellent bone regeneration environment that resulted in better outcomes of bone regeneration in a femur defect rat model compared to those with SCNFs possessed fewer carboxylate groups. In conclusion, biomaterial scaffolds based on TEMPO-oxidized SCNFs produced from one-pot fabricated SC showed great potential for bone regeneration due to unique physical and chemical properties.