Resveratrol (3,5,49-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-c coactivator 1a (PGC-1a) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing.

/pdf/resveratrol-improves-health-and-survival-of-mice-on-a-high-nclsf2ace3.pdf

Resveratrol improves health and survival of mice on a high-calorie diet

Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

Gastric cancer is the third leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability (MSI) status, and the expression of programmed death-ligand 1 (PD-L1), has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with localized gastric cancer. This selection from the NCCN Guidelines for Gastric Cancer focuses on the management of unresectable locally advanced, recurrent, or metastatic disease.

Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Nonalcoholic fatty liver disease (NAFLD) is characterized by insulin resistance, which results in elevated serum concentration of free fatty acids (FFAs). Circulating FFAs provide the substrate for triacylglycerol formation in the liver, and may also be directly cytotoxic. Hepatocyte apoptosis is a key histologic feature of NAFLD, and correlates with progressive inflammation and fibrosis. The molecular pathways leading to hepatocyte apoptosis are not fully defined; however, recent studies suggest that FFA-induced apoptosis contributes to the pathogenesis of nonalcoholic steatohepatitis. FFAs directly engage the core apoptotic machinery by activating the proapoptotic protein Bax, in a c-jun N-terminal kinase-dependent manner. FFAs also activate the lysosomal pathway of cell death and regulate death receptor gene expression. The role of ER stress and oxidative stress in the pathogenesis of nonalcoholic steatohepatitis has also been described. Understanding the molecular mediators of liver injury should promote development of mechanism-based therapeutic interventions.

Molecular mechanisms of lipotoxicity in nonalcoholic fatty liver disease.

https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.21768

Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis: present and future.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause for elevated liver enzymes in the developed nations. Beyond prevention programs which are of particular interest because of the increasing number of overweight children, treatment should be focussed on the most important risk factors, obesity and insulin resistance. As a consequence of elucidating the pathomechanisms of NAFLD, the number of potential therapeutic options increased. However, many studies investigating the therapeutic effect show shortcomings in at least one of the following points: lack of a serial liver biopsy, short term of treatment and limited number of included patients. The second generation insulin sensitizer pioglitazone and rosiglitazone show the most promising improvements in NAFLD, but weight gain and potential hepatotoxicity calls for attention. In conclusion, a general recommendation for the application of specific drugs cannot be given. Besides controlled clinical trials, weight reduction and physical activity to improve insulin sensitivity in obese patients should be the priority objective.

pdf/treatment-of-nonalcoholic-fatty-liver-disease-vmcxs0bd81.pdf

Treatment of nonalcoholic fatty liver disease

Background and study aims The full-thickness resection device (FTRD) represents a novel endoscopic treatment method for lesions unresectable with conventional endoscopic techniques. The overall aim of this study was to evaluate technical success and in toto resection rates, recurrence rates, as well as immediate or late complications in patients who underwent polyp removal with the FTRD. Patients and methods Data from a prospectively collected database of 12 patients who underwent 13 over-the-scope clip-based full-thickness resections between June 2015 and June 2017 were analyzed. Follow-up endoscopy was performed in 11 out of 12 patients. Results 13 full-thickness resections were performed in 7 males and 5 females (mean age 64.3 ± 6.3 years). Mean size of the lesions removed with FTRD was 17 ± 4 mm. Location was rectum (n = 6), cecum (n = 2), ascending colon (n = 2), left flexure (n = 1) and right flexure (n = 2). Mean procedure time was 68 ± 35 minutes and mean hospital stay was 2.5 ± 1.2 days. 2 patients developed post-polypectomy syndrome, which resolved after conservative treatment. No perforations and no immediate surgical revision were needed. Histology of the 13 lesions removed with FTRD showed 5 adenomas with low grade intraepithelial neoplasia (IEN), 4 high grade IEN, 1 fibrosis, 1 fibrosis without dysplasia and 2 adenocarcinomas. Technical success was achieved in all procedures (13/13, 100 %). R0 resection was achieved in 10/12 patients (83.3 %). 2 patients underwent surgery because of recurrence or not evaluable margins. In 1 patient no residual malignancy was proven in histological examination, in the other patient residual low grade IEN adenoma. Conclusion FTRD is a minimally invasive approach with good success rate of complete resection and minimal side effects.

/pdf/endoscopic-full-thickness-resection-with-an-over-the-scope-2n4w6ue2y5.pdf

Endoscopic full-thickness resection with an over-the-scope clip device (FTRD) in the colorectum: results from a university tertiary referral center.

Background Gastrointestinal (GI) bleeding is a common indication for endoscopy For refractory cases, hemostatic powders (HP) represent "touch-free" agents Aim To analyze short term (ST-within 72 h-) and long-term (LT-within 30 d-) success for achieving hemostasis with HP and to directly compare the two agents Hemospray (HS) and Endoclot (EC) Methods HP was applied in 154 consecutive patients (mean age 67 years) with GI bleeding Patients were followed up for 1 mo (mean follow-up: 32 mo) Results Majority of applications were in upper GI tract (89%) with following bleeding sources: peptic ulcer disease (35%), esophageal varices (7%), tumor bleeding (117%), reflux esophagitis (87%), diffuse bleeding and erosions (153%) Overall ST success was achieved in 125 patients (81%) and LT success in 81 patients (67%) Re-bleeding occurred in 27% of all patients In 72 patients (47%), HP was applied as a salvage hemostatic therapy, here ST and LT success were 81% and 64%, with re-bleeding in 32% As a primary hemostatic therapy, ST and LT success were 82% and 69%, with re-bleeding occurring in 22% HS was more frequently applied for upper GI bleeding (P = 004) Conclusion Both HP allow for effective hemostasis with no differences in ST, LT success and re-bleeding

Comparison of Hemospray® and Endoclot™ for the treatment of gastrointestinal bleeding.

https://www.gastrojournal.org/article/S0016-5085(06)02262-1/pdf

IL-28A is a key regulator of T-cell-mediated liver injury via the T-box transcription factor T-bet.

Although 5-fluorouracil remains the mainstay of treatment for advanced gastric cancer (AGC), no standard chemotherapy regimen exists. Combinations of irinotecan with folinic acid and infusional 5-fluorouracil (5-FU) (ILF) have shown good efficacy with acceptable toxicity in patients with metastatic

Weekly treatment with irinotecan, folinic acid and infusional 5-fluorouracil (ILF) in patients with advanced gastric cancer.

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