Assessing herpes zoster vaccine efficacy in patients with diabetes: A community-based cohort study.

The effectiveness of herpes zoster (HZ) vaccines in patients with diabetes over the age of 50 remains an active area of research. Utilizing a real-world database from the US community, this study spanning from 2006 to 2023, aimed to evaluate the impact of HZ vaccination on newly diagnosed diabetes patients who received an HZ vaccination within 1 year of diagnosis. Exclusion criteria were established to omit patients with immune deficiencies. The cohort consisted of 53 885 patients, with an average age of 63.5 years, including 43% females and 58% whites. After implementing 1:1 propensity score matching for age, sex, race, comorbidities, diabetes medication, and hemoglobin A1c to ensure comparability, the study population was further stratified into four groups: N1 comparing any HZ vaccination to non-HZ vaccination (53 882 matched pairs), N2 for Shingrix versus non-HZ vaccination (16 665 matched pairs), N3 for Zostavax versus non-HZ vaccination (12 058 matched pairs), and N4 for Shingrix versus Zostavax (11 721 matched pairs). Cox proportional hazards regression analysis revealed a hazard ratio (HR) for HZ incidence post any HZ vaccination of 0.92 (95% confidence interval [CI]: 0.83-1.01). Additional analyses yielded HRs of 1.12 (95% CI: 0.93-1.34) for Shingrix versus non-HZ vaccine, 1.02 (95% CI: 0.86-1.20) for Zostavax versus non-HZ vaccine, and 1.06 (95% CI: 0.87-1.29) for Shingrix versus Zostavax. Subgroup analyses across age, sex, and follow-up duration also showed no significant differences. These findings underscore the lack of a significant benefit from HZ vaccination in newly diagnosed diabetes patients aged over 50, highlighting the necessity for further prospective research.

Improving the Effects of Mulberry Leaves and Neochlorogenic Acid on Glucotoxicity-Induced Hepatic Steatosis in High Fat Diet Treated db/db Mice.

There are many complications of type 2 diabetes mellitus. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are two complications related to the increased lipid accumulation in the liver. Previous studies have shown that mulberry leaf water extract (MLE) has the effect of lowering lipid levels in peripheral blood, inhibiting the expression of fatty acid synthase (FASN) and increasing the activity of liver antioxidant enzymes superoxide dismutase (SOD) and catalase. Our study aimed to investigate the role of MLE and its main component, neochlorogenic acid (nCGA), in reducing serum lipid profiles, decreasing lipid deposition in the liver, and improving steatohepatitis levels. We evaluated the antioxidant activity including glutathione (GSH), glutathione reductase (GRd), glutathione peroxidase (GPx), glutathione S-transferase (GST), and superoxide dismutase (SOD), and catalase was tested in mice fed with MLE and nCGA. The results showed a serum lipid profile, and fatty liver scores were significantly increased in the HFD group compared to the db/m and db mice groups, while liver antioxidant activity significantly decreased in the HFD group. When fed with HFD + MLE or nCGA, there was a significant improvement in serum lipid profiles, liver fatty deposition conditions, steatohepatitis levels, and liver antioxidant activity compared to the HFD group. Although MLE and nCGA do not directly affect the blood sugar level of db/db mice, they do regulate abnormalities in lipid metabolism. These results demonstrate the potential of MLE/nCGA as a treatment against glucotoxicity-induced diabetic fatty liver disease in animal models.

Association between Cholecystectomy and the Incidence of Pancreaticobiliary Cancer after Endoscopic Choledocholithiasis Management.

(1) Background: Previous studies have raised concerns about a potential increase in pancreaticobiliary cancer risk after cholecystectomy, but few studies have focused on patients who undergo cholecystectomy after receiving endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis. This study aims to clarify cancer risks in these patients, who usually require cholecystectomy, to reduce recurrent biliary events. (2) Methods: We conducted a nationwide cohort study linked to the National Health Insurance Research Database, the Cancer Registry Database, and the Death Registry Records to evaluate the risk of pancreaticobiliary cancers. All patients who underwent first-time therapeutic ERCP for choledocholithiasis from 2011 to 2017 in Taiwan were included. We collected the data of 13,413 patients who received cholecystectomy after endoscopic retrograde cholangiopancreatography and used propensity score matching to obtain the data of 13,330 patients in both the cholecystectomy and non-cholecystectomy groups with similar age, gender, and known pancreaticobiliary cancer risk factors. Pancreaticobiliary cancer incidences were further compared. (3) Results: In the cholecystectomy group, 60 patients had cholangiocarcinoma, 61 patients had pancreatic cancer, and 15 patients had ampullary cancer. In the non-cholecystectomy group, 168 cases had cholangiocarcinoma, 101 patients had pancreatic cancer, and 49 patients had ampullary cancer. The incidence rates of cholangiocarcinoma, pancreatic cancer, and ampullary cancer were 1.19, 1.21, and 0.3 per 1000 person-years in the cholecystectomy group, all significantly lower than 3.52 (p < 0.0001), 2.11 (p = 0.0007), and 1.02 (p < 0.0001) per 1000 person-years, respectively, in the non-cholecystectomy group. (4) Conclusions: In patients receiving ERCP for choledocholithiasis, cholecystectomy is associated with a significantly lower risk of developing pancreaticobiliary cancer.

Association of COVID-19 Infection with Subsequent Thyroid Dysfunction: An International Population-Based Propensity Score Matched Analysis.

Background: The COVID-19 pandemic's impact on thyroid function is a growing concern. Previous studies have produced inconclusive results, and there is a lack of comprehensive research into the long-term risks of thyroid dysfunction following COVID-19 infection. Methods: In this retrospective cohort study, we used data from the TriNetX international database, which includes electronic health records from a broad, diverse patient population. We compared patients with COVID-19 (cases) to those without (controls), matching for age, sex, race, and comorbidities using propensity score matching. The primary outcome was the diagnosis of thyroid dysfunction (thyrotoxicosis or hypothyroidism) within a 12-month period, analyzed using hazard ratios (HRs) and Kaplan-Meier curves, and stratified by age and sex. Results: Initially, the study included 1,379,311 COVID-19 patients and 6,896,814 non-COVID-19 patients from the TriNetX database. After matching, the cohorts were comparable in demographics and baseline characteristics. This study consistently demonstrated a significant increase in the risk of thyroid dysfunction, including thyrotoxicosis and hypothyroidism, among COVID-19 patients compared to non-COVID-19 patients. In the short term (3 months postexposure), the COVID-19 group exhibited a HR of 2.07 (95% confidence interval [CI] 2.01-2.12) for thyroid dysfunction, which included both thyrotoxicosis (HR 2.10, CI 1.92-2.29) and hypothyroidism (HR 2.08, CI 2.01-2.13). This heightened risk persisted over the long term (up to 12 months), with HRs indicating an ∼2.01-fold increased risk for overall thyroid dysfunction, a 1.8-fold increased risk for thyrotoxicosis, and a 2.04-fold increased risk for hypothyroidism. Subgroup analysis, stratified by age and sex, revealed a notably higher risk of thyroid dysfunction in patients aged 65 and above (HR 2.18, CI 2.11-2.25), compared to those in the under-65 age group (HR 1.97, CI 1.91-2.03). Both male and female patients were associated with an elevated risk, with females showing a slightly higher association with thyroid dysfunction (HR 2.12, CI 2.06-2.16) compared to males (HR 1.76, CI 1.69-1.82). Conclusions: COVID-19 infection was associated with an increased risk of thyroid dysfunction, including thyrotoxicosis and hypothyroidism, regardless of age or sex, during a 12-month follow-up period. Further research is required to validate these findings.

PNU-74654 Induces Cell Cycle Arrest and Inhibits EMT Progression in Pancreatic Cancer.

Background and Objectives: PNU-74654, a Wnt/ß-catenin pathway inhibitor, has an antiproliferative effect on many cancer types; however, its therapeutic role in pancreatic cancer (PC) has not yet been demonstrated. Here, the effects of PNU-74654 on proliferation and cell cycle phase distribution were studied in PC cell lines. Materials and Methods: The cancer-related molecular pathways regulated by PNU-74654 were determined by a proteome profiling oncology array and confirmed by western blotting. Results: The cell viability and proliferative ability of PC cells were decreased by PNU-74654 treatment. G1 arrest was observed, as indicated by the downregulation of cyclin E and cyclin-dependent kinase 2 (CDK2) and the upregulation of p27. PNU-74654 inhibited the epithelial-mesenchymal transition (EMT), as determined by an increase in E-cadherin and decreases in N-cadherin, ZEB1, and hypoxia-inducible factor-1 alpha (HIF-1α). PNU-74654 also suppressed cytoplasmic and nuclear ß-catenin and impaired the NF-κB pathway. Conclusions: These results demonstrate that PNU-74654 modulates G1/S regulatory proteins and inhibits the EMT, thereby suppressing PC cell proliferation, migration, and invasion. The synergistic effect of PNU-74654 and chemotherapy or the exclusive use of PNU-74654 may be therapeutic options for PC and require further investigation.

Hibiscus Anthocyanins Extracts Induce Apoptosis by Activating AMP-Activated Protein Kinase in Human Colorectal Cancer Cells.

Apoptosis, a programmed cell death process preventing cancer development, can be evaded by cancer cells. AMP-activated protein kinase (AMPK) regulates energy levels and is a key research topic in cancer prevention and treatment. Some bioactive components of Hibiscus sabdariffa L. (HAs), including anthocyanins, have potential anticancer properties. Our study investigated the in vitro cytotoxic potential and mode of action of HAs extracts containing anthocyanins in colorectal cancer cells. The results showed that Hibiscus anthocyanin-rich extracts induced apoptosis in human colorectal cancer cells through the activation of multiple signaling pathways of AMPK. We observed the dose-response and time-dependent induction of apoptosis with HAs. Subsequently, the activation of Fas-mediated proteins triggered apoptotic pathways associated with Fas-mediated apoptosis-related proteins, including caspase-8/tBid. This caused the release of cytochrome C from the mitochondria, resulting in caspase-3 cleavage and apoptosis activation in intestinal cancer cells. These data elucidate the relationship between Has' regulation of apoptosis-related proteins in colorectal cancer cells and apoptotic pathways.

Glucosinolates Extracts from Brassica juncea Ameliorate HFD-Induced Non-Alcoholic Steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) is mainly characterized by excessive fat accumulation in the liver. It spans a spectrum of diseases from hepatic steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Brassica juncea is rich in glucosinolates and has been proven to possess many potential pharmacological properties, including hypoglycemic, anti-oxidation, anti-inflammatory, and anti-carcinogenic activities. This study aims to investigate whether whole-plant Brassica juncea (WBJ) and its glucosinolates extracts (BGE) have hepatoprotective effects against a high-fat diet (HFD)-induced NAFLD and further explore the mechanism underlying this process in vivo and in vitro. WBJ treatment significantly reduced body fat, dyslipidemia, hepatic steatosis, liver injury, and inflammation; WBJ treatment also reversed the antioxidant enzyme activity to attenuate oxidative stress in HFD-fed rat liver. Moreover, WBJ and BGE enhanced the activation of AMPK to reduce SREBPs, fatty acid synthase, and HMG-CoA reductase but increased the expression of CPT-I and PPARα to improve hepatic steatosis. In addition, WBJ and BGE could ameliorate NAFLD by inhibiting TNF-α and NF-κB. Based on the above results, this study demonstrates that WBJ and BGE ameliorate HFD-induced hepatic steatosis and liver injury. Therefore, these treatments could represent an unprecedented hope toward improved strategies for NAFLD.

Hypothetical hypoxia-driven rapid disease progression in hepatocellular carcinoma post transarterial chemoembolization: A case report.

BACKGROUND: Transarterial chemoembolization (TACE) is widely performed for intermediate-stage or unresectable hepatocellular carcinoma (HCC), but approximately half of patients do not respond to TACE treatment. We describe a case of rapidly progressing of HCC after TACE and provide a possible hypothesis for this condition. The finding may contribute to identifying patients who obtain less benefit from TACE, thus avoiding the unnecessary waste of medical resources and treatment during the golden hour window. CASE SUMMARY: A 61-year-old woman had been diagnosed with chronic hepatitis B infection and HCC at Barcelona Clinic Liver Cancer stage B, which had been treated by segmental hepatectomy 14 mo ago. The tumor recurred in the two months after surgery. She received an initial TACE and then underwent systemic therapy with lenvatinib 8 mg daily due to an increased level of alpha-fetoprotein (AFP) after the first TACE. However, the tumor continued to progress with an increased level of AFP, and she underwent a second TACE, after which the tumor volume did not obviously decrease on the contrast-enhanced computed tomography image. One month later, she had a third TACE to control the residual HCC tumors. Two weeks after that, the HCC had increased dramatically with tea-colored urine and yellowish skin turgor. Eventually, the patient refused further treatment and went into hospice care. CONCLUSION: Intense hypoxia induced by TACE can trigger rapid disease progression in infiltrative HCC patients with a large tumor burden.

Improved Trends in the Mortality-to-Incidence Ratios for Liver Cancer in Countries with High Development Index and Health Expenditures.

Primary liver cancer is one of the leading causes of death globally. Liver cancer has a unique geographical distribution, as its etiologies include chronic viral infections and aging. We hypothesize that the human development index (HDI), current health expenditure (CHE) per capita, and CHE-to-gross domestic product ratio (CHE/GDP) influence the incidence, mortality, and mortality-to-incidence ratios (MIRs) of liver cancer worldwide. Data were obtained from the Global Cancer Observatory (GLOBOCAN) database and the World Health Organization. MIRs and the changes in MIR over time (δMIR) were used to evaluate the correlation of expenditures on healthcare and the HDI disparities via Spearman's rank correlation coefficient. The crude incidence and mortality were significantly associated with HDI, CHE per capita, and CHE/GDP. Specifically, there were significant associations between δMIR and HDI, as well as between δMIR and CHE per capita. However, there were no significant associations between δMIR and CHE/GDP. Evidently, a favorable liver cancer δMIR was not associated with CHE/GDP, although it had a significant association with HDI and CHE per capita. These results are worthy of the attention of public health systems in correlation to improved outcomes in liver cancer.

Artificial intelligence system for the detection of Barrett's esophagus.

BACKGROUND: Barrett's esophagus (BE), which has increased in prevalence worldwide, is a precursor for esophageal adenocarcinoma. Although there is a gap in the detection rates between endoscopic BE and histological BE in current research, we trained our artificial intelligence (AI) system with images of endoscopic BE and tested the system with images of histological BE. AIM: To assess whether an AI system can aid in the detection of BE in our setting. METHODS: Endoscopic narrow-band imaging (NBI) was collected from Chung Shan Medical University Hospital and Changhua Christian Hospital, resulting in 724 cases, with 86 patients having pathological results. Three senior endoscopists, who were instructing physicians of the Digestive Endoscopy Society of Taiwan, independently annotated the images in the development set to determine whether each image was classified as an endoscopic BE. The test set consisted of 160 endoscopic images of 86 cases with histological results. RESULTS: Six pre-trained models were compared, and EfficientNetV2B2 (accuracy [ACC]: 0.8) was selected as the backbone architecture for further evaluation due to better ACC results. In the final test, the AI system correctly identified 66 of 70 cases of BE and 85 of 90 cases without BE, resulting in an ACC of 94.37%. CONCLUSION: Our AI system, which was trained by NBI of endoscopic BE, can adequately predict endoscopic images of histological BE. The ACC, sensitivity, and specificity are 94.37%, 94.29%, and 94.44%, respectively.

An Improved Endoscopic Automatic Classification Model for Gastroesophageal Reflux Disease Using Deep Learning Integrated Machine Learning.

Gastroesophageal reflux disease (GERD) is a common digestive tract disease, and most physicians use the Los Angeles classification and diagnose the severity of the disease to provide appropriate treatment. With the advancement of artificial intelligence, deep learning models have been used successfully to help physicians with clinical diagnosis. This study combines deep learning and machine learning techniques and proposes a two-stage process for endoscopic classification in GERD, including transfer learning techniques applied to the target dataset to extract more precise image features and machine learning algorithms to build the best classification model. The experimental results demonstrate that the performance of the GerdNet-RF model proposed in this work is better than that of previous studies. Test accuracy can be improved from 78.8% ± 8.5% to 92.5% ± 2.1%. By enhancing the automated diagnostic capabilities of AI models, patient health care will be more assured.

Gallstone associated celiac trunk thromboembolisms complicated with splenic infarction: A case report.

BACKGROUND: Gallstone disease (GD) can have prolonged, subacute inflammatory period before biliary events. The intricate relationship between GD and inflammatory processes can possible lead to prothrombotic tendency that can result in confusing clinical course before diagnosis. CASE SUMMARY: A 51-year-old man, presented with a 1-year history of self-relief occasional postprandial upper abdominal pain, had sudden onset severe left upper quadrant pain and visited our emergency room. Contrast enhanced computed tomography (CECT) showed filling defect in celiac trunk, common hepatic, part of splenic arteries and wedge-shaped hypo-enhancing region of spleen, consistent with splenic infarction secondary to splenic arterial occlusion. No convincing predisposing factors were found during first hospitalization. Abdominal pain mildly subsided after low molecular weight heparin and bridge to oral anticoagulant use. However, in the following six months, the patient was admitted twice due to acute cholangitis and finally cholecystitis. Second CECT revealed biliary impacted stone was adjacent to poor dissoluble thrombus. The abdominal pain did not achieve a clinical full remission until endoscopic retrograde cholangiopancreatography stone removal and series laparoscopic cholecystectomy was performed. CONCLUSION: This is the first case to present serious thrombotic complication due to inflammation status in chronic GD. It could be a rare, confusing and difficult recognizing cause of a celiac trunk thromboembolic event.

The Therapeutic Role of PNU-74654 in Hepatocellular Carcinoma May Involve Suppression of NF-κB Signaling.

Background and Objectives: PNU-74654, a Wnt/ß-catenin inhibitor, has reported antitumor activities; however, the therapeutic potential of PNU-74654 in hepatocellular carcinoma (HCC) has not been investigated in detail. The aim of this study was to clarify the cytotoxic effects of PNU-74654 against HCC and to uncover its molecular mechanism. Materials and Methods: HepG2 and Huh7 liver cancer cell lines were selected to determine the antitumor properties of PNU-74654. Survival of the liver cancer cells in response to PNU-74654 was assessed by cell viability assays, and the apoptosis effect of PNU-74654 was analyzed by flow cytometry and visualized by Hoechst staining. An oncology array was used to explore the underlying molecular routes of PNU-74654 action in the cells. The migration properties were examined with a wound healing assay, and western blotting was conducted to evaluate protein expression. Results: Treatment with PNU-74654 decreased cell viability and inhibited cell migration. The cell cycle analysis and Hoechst staining revealed an increase in the population of cells at the sub-G1 stage and apoptotic morphological changes in the nucleus. The oncology array identified 84 oncology-related proteins and a suppressed expression of Bcl-xL and survivin. Western blotting showed that PNU-74654 could interfere with cell cycle-related proteins through the NF-κB pathway. Conclusions: PNU-74654 shows antiproliferative and antimigration effects against HepG2 and Huh7 cells, and its antitumor activity may be attributable to its interference in cell cycle regulation and the NF-κB pathway.

Primary malignant peritoneal mesothelioma mimicking tuberculous peritonitis: A case report.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare malignancy arising in mesothelial cells in the peritoneum. It can be mistaken for many other diseases, such as peritoneal carcinomatosis and tuberculous peritonitis (TBP), because its clinical manifestations are often nonspecific. Therefore, the diagnosis of MPM is often challenging and delayed. CASE SUMMARY: A 42-year-old man was referred to our hospital with lower abdominal pain for 1 wk and ascites observed under abdominal sonography. His laboratory findings revealed an isolated elevated tumor marker of carcinoma antigen 125 (167.4 U/mL; normal, < 35 U/mL), and contrast enhanced computed tomography showed peritoneal thickening. Thus, differential diagnoses of TBP, carcinomatosis of an unknown nature, and primary peritoneal malignancy were considered. After both esophagogastroduodenoscopy and colonoscopy produced negative findings, laparoscopic intervention was performed. The histopathological results revealed mesothelioma invasion into soft tissue composed of a papillary, tubular, single-cell arrangement of epithelioid cells. In addition, immunohistochemical staining was positive for mesothelioma markers and negative for adenocarcinoma markers. Based on the above findings, TBP was excluded, and the patient was diagnosed with MPM. CONCLUSION: It is important to distinguish MPM from TBP because they have similar symptoms and blood test findings.

Intragastric injection of botulinum toxin A for weight loss: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Intragastric botulinum toxin A (BTA) injection is a potential treatment for weight reduction in obese patients. Current studies yielded conflicting results. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the efficacy of intragastric BTA injection for weight management. METHODS: We searched several databases to identify RCTs evaluating intragastric BTA injections for obesity. We applied random-effects models for all meta-analyses due to heterogeneity in the included studies. The mean difference (MD) and 95% confidence interval (CI) were calculated for continuous outcomes. RESULTS: A total of 6 RCTs including 192 subjects met the inclusion criteria and were included for the meta-analysis. Although the pooled data from six studies showed no difference in the absolute weight loss between intragastric BTA injection and control, subgroup analysis showed a significantly decreased absolute weight after a BTA injection dose ≥ 200 U (MD, -2.04 kg; 95% CI, -3.96 to -0.12) and after multiple injection regions in the stomach combined with diet control (MD, -4.44 kg; 95% CI, -6.54 to -2.33 kg) compared with the control. Regarding absolute weight loss, the impact of endoscopic ultrasound-guided injection and follow-up duration showed no difference. Intragastric BTA injection had a significant change in body mass index (MD, -1.25 kg/m2 ; 95% CI, -2.18 to -0.32 kg/m2 ) and prolonged gastric half-emptying time (MD, 11.37 min; 95% CI, -3.69 to 19.06 min). CONCLUSION: Intragastric BTA injection is effective for obesity treatment, and adequate doses (≥ 200 U), multiple gastric injection regions, and combined diet control are crucial. However, given the small sample size and limited power, caution should be exercised.

The effect of coffee/caffeine on postoperative ileus following elective colorectal surgery: a meta-analysis of randomized controlled trials.

PURPOSE: Postoperative ileus (POI) is the most common complication of elective colon resection. Coffee or caffeine has been reported to be useful in improving gastrointestinal function after abdominal surgery. This study aimed to investigate the effect of coffee/caffeine on POI in patients undergoing elective colorectal surgery. METHODS: We searched Cochrane library, Embase, PubMed, and ClinicalTrials.gov (until July 2021) to identify randomized controlled trials (RCTs) evaluating the effect of coffee or caffeine on bowel movements and POI in patients undergoing elective colorectal surgery. The mean difference (MD) for continuous outcomes and risk ratio (RR) for dichotomous outcomes were calculated and are presented with 95% confidence intervals (CIs). A random effects model was used in all meta-analyses. RESULTS: A total of four RCTs including 312 subjects met the inclusion criteria and were included in the meta-analysis. Postoperative coffee or caffeine consumption decreased the time to first bowel movement (MD, - 10.36 h; 95% CI, - 14.61 to - 6.11), shortened the length of hospital stay (MD, - 0.95 days; 95% CI, - 1.57 to - 0.34), and was associated with a decreased risk of the use of any laxatives after the procedure (RR, 0.64; 95% CI, 0.44 to 0.92). The time to first flatus, time to tolerance of solid food, risk of any postoperative complication, postoperative reinsertion of a nasogastric (NG) tube, and anastomotic leakage showed no statistical differences between groups. CONCLUSION: Postoperative coffee or caffeine consumption improved bowel movement and decreased the duration of hospital stay in patients undergoing elective colorectal surgery. This method is safe and can prevent or treat POI.

Neochlorogenic Acid Attenuates Hepatic Lipid Accumulation and Inflammation via Regulating miR-34a In Vitro.

Neochlorogenic acid (5-Caffeoylquinic acid; 5-CQA), a major phenolic compound isolated from mulberry leaves, possesses anti-oxidative and anti-inflammatory effects. Although it modulates lipid metabolism, the molecular mechanism is unknown. Using an in-vitro model of nonalcoholic fatty liver disease (NAFLD) in which oleic acid (OA) induced lipid accumulation in HepG2 cells, we evaluated the alleviation effect of 5-CQA. We observed that 5-CQA improved OA-induced intracellular lipid accumulation by downregulating sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN) expression, which regulates the fatty acid synthesis, as well as SREBP2 and HMG-CoA reductases (HMG-CoR) expressions, which regulate cholesterol synthesis. Treatment with 5-CQA also increased the expression of fatty acid ß-oxidation enzymes. Remarkably, 5-CQA attenuated OA-induced miR-34a expression. A transfection assay with an miR-34a mimic or miR-34a inhibitor revealed that miR-34a suppressed Moreover, Sirtuin 1 (SIRT1) expression and inactivated 5' adenosine monophosphate-activated protein kinase (AMPK). Our results suggest that 5-CQA alleviates lipid accumulation by downregulating miR-34a, leading to activation of the SIRT1/AMPK pathway.

Mulberry Leaf Polyphenol Extract and Rutin Induces Autophagy Regulated by p53 in Human Hepatoma HepG2 Cells.

The edible leaves of the mulberry (Morus alba L.) plant are used worldwide. They contain abundant polyphenolic compounds with strong anticancer properties. We previously revealed that apoptosis was mediated in p53-negative Hep3B cells, and mulberry leaf polyphenol extract (MLPE) induced autophagy in p53-transfected Hep3B cells. However, how this autophagy is induced by p53 in human hepatoma HepG2 (p53 wild type) cells remains unclear. In the current study, MLPE induced autophagy, as demonstrated by enhanced acidic vesicular organelle staining, by upregulating beclin-1, increasing LC3-II conversion, and phosphorylating AMPK. In HepG2 cells, these processes were associated with p53. Western blot also revealed phosphatidylinositol-3 kinase (PI3K), p-AKT, and fatty acid synthase (FASN) suppression in MLPE-treated cells. Moreover, treatment with the p53 inhibitor pifithrin-α (PFT-α) inhibited autophagy and increased apoptotic response in MLPE-treated HepG2 cells. PFT-α treatment also reversed MLPE-induced PI3K, p-AKT, and FASN suppression. Thus, co-treatment with MLPE and PFT-α significantly increased caspase-3, caspase-8, and cytochrome c release, indicating that p53 deficiency caused the apoptosis. In addition, rutin, a bioactive polyphenol in MLPE, may affect autophagy in HepG2 cells. This study demonstrates that MLPE is a potential anticancer agent targeting autophagy and apoptosis in cells with p53 status. Moreover, this work provides insight into the mechanism of p53 action in MLPE-induced cytotoxicity in hepatocellular carcinoma.