Mallikarjuna Rao Pichika’s Post

Diet intervention (ketogenic diet and intermittent fasting) combined with a P-eIF4E inhibitor to reduce pancreatic cancer growth showed in this preclinical study. Check out this new interesting paper!

Cool paper in Cell Metabolism: A 5:2 intermittent fasting regimen ameliorates NASH and fibrosis and blunts HCC development via hepatic PPARα and PCK1 https://lnkd.in/eAx-DmSk The role and molecular mechanisms of intermittent fasting (IF) in non-alcoholic steatohepatitis (NASH) and its transition to hepatocellular carcinoma (HCC) are unknown. Here, we identified that an IF 5:2 regimen prevents NASH development as well as ameliorates established NASH and fibrosis without affecting total calorie intake. Furthermore, the IF 5:2 regimen blunted NASH-HCC transition when applied therapeutically. The timing, length, and number of fasting cycles as well as the type of NASH diet were critical parameters determining the benefits of fasting. Combined proteome, transcriptome, and metabolome analyses identified that peroxisome-proliferator-activated receptor alpha (PPARα) and glucocorticoid-signaling-induced PCK1 act co-operatively as hepatic executors of the fasting response. In line with this, PPARα targets and PCK1 were reduced in human NASH. Notably, only fasting initiated during the active phase of mice robustly induced glucocorticoid signaling and free-fatty-acid-induced PPARα signaling. However, hepatocyte-specific glucocorticoid receptor deletion only partially abrogated the hepatic fasting response. In contrast, the combined knockdown of Ppara and Pck1 in vivoabolished the beneficial outcomes of fasting against inflammation and fibrosis. Moreover, overexpression of Pck1alone or together with Ppara in vivo lowered hepatic triglycerides and steatosis. Our data support the notion that the IF 5:2 regimen is a promising intervention against NASH and subsequent liver cancer.

Very happy to share our recent publication in Cancer Research entitled "Obesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer" https://lnkd.in/d5dpyGUf In this study we show that saturated fatty acid-enriched obesogenic diet increases the levels of the oncometabolite lactate promoting tumor microenvironment remodeling and prostate cancer progression. A further step towards a better understanding how diet/obesity influence prostate cancer progression. Our work highlights the importance of approaches of dietary intervention/precision nutrition alongside standard of care in the management of patients with advanced prostate cancer. Many thanks to the fantastic team of collaborators, co-first authors Nadia Boufaied and Paolo Chetta, co-leader David Labbé , and WCRF funding! #metabolism #microenvironment #cancer #prostate #lactate #PCa #diet #myc

SGLT2 inhibition eliminates senescent cells and alleviates pathological aging It has been reported that accumulation of senescent cells in various tissues contributes to pathological aging and that elimination of senescent cells (senolysis) improves age-associated pathologies. The researchers demonstrate that inhibition of sodium–glucose co-transporter 2 (SGLT2) enhances clearance of senescent cells, thereby ameliorating age-associated phenotypic changes. In a mouse model of dietary obesity, short-term treatment with the SGLT2 inhibitor canagliflozin reduced the senescence load in visceral adipose tissue and improved adipose tissue inflammation and metabolic dysfunction, but normalization of plasma glucose by insulin treatment had no effect on senescent cells. Canagliflozin extended the lifespan of mice with premature aging even when treatment was started in middle age. Metabolomic analyses revealed that short-term treatment with canagliflozin upregulated 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, enhancing immune-mediated clearance of senescent cells by downregulating expression of programmed cell death-ligand 1. These findings suggest that inhibition of SGLT2 has an indirect senolytic effect by enhancing endogenous immunosurveillance of senescent cells. https://lnkd.in/gzjQBD7d

Will Metabolic Therapy Revolutionize Cancer Treatment in the Future? (Part Two) The Role of Diet in Metabolic Therapy Diet plays a central role in Seyfried’s metabolic therapy. He advocates for a ketogenic diet, which restricts carbohydrates and forces the body to shift from burning glucose to burning ketones, a more efficient fuel source derived from fat. In this state of nutritional ketosis, normal cells can thrive, while cancer cells—unable to use ketones effectively—struggle to survive. Coupled with calorie restriction and even water-only fasting, Seyfried believes this dietary approach can lower the body’s glucose availability, starving cancer cells of their primary energy source. By monitoring the Glucose-Ketone Index (GKI), individuals can track their metabolic state and ensure their bodies are less hospitable to cancer cell growth. Metabolic Therapy in Cancer Treatment For cancer patients, Seyfried’s metabolic therapy can serve as an adjunct to traditional treatments like chemotherapy and radiation. By creating a hostile environment for cancer cells through diet and lifestyle changes, metabolic therapy can make conventional treatments more effective, possibly even reducing the required dosage and side effects. In addition to diet, Seyfried advocates for targeting glutamine, the other key fuel cancer cells use to grow. While still under investigation, certain drugs and strategies may be developed to block glutamine pathways, further weakening cancer cells. Another component of Seyfried’s approach is hyperbaric oxygen therapy, which involves exposing the body to higher levels of oxygen. This therapy can work synergistically with a ketogenic diet, as cancer cells weakened by nutrient restriction are further damaged by the increased oxygen levels, while healthy cells remain unharmed. #CancerTreatment #CancerMetabolism #HyperbaricOxygen #CancerAwareness #Cancer #Mitochondria #Chemotherapy #Radiation #Surgery #Oncology

Interesting in Cell Metabolism: Dual impacts of serine/glycine-free diet in enhancing antitumor immunity and promoting evasion via PD-L1 lactylation https://lnkd.in/e2EmKK6u The effect of the serine/glycine-free diet (−SG diet) on colorectal cancer (CRC) remains unclear; meanwhile, programmed death-1 (PD-1) inhibitors are less effective for most CRC patients. Here, we demonstrate that the −SG diet inhibits CRC growth and promotes the accumulation of cytotoxic T cells to enhance antitumor immunity. Additionally, we also identified the lactylation of programmed death-ligand 1 (PD-L1) in tumor cells as a mechanism of immune evasion during cytotoxic T cell-mediated antitumor responses, and blocking the PD-1/PD-L1 signaling pathway is able to rejuvenate the function of CD8+ T cells recruited by the −SG diet, indicating the potential of combining the −SG diet with immunotherapy. We conducted a single-arm, phase I study (ChiCTR2300067929). The primary outcome suggests that the −SG diet is feasible and safe for regulating systemic immunity. Secondary outcomes include patient tolerability and potential antitumor effects. Collectively, our findings highlight the promising therapeutic potential of the −SG diet for treating solid tumors..

📃Scientific paper: Association between pre-diagnostic circulating lipid metabolites and colorectal cancer risk: a nested case–control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) Abstract: BACKGROUND: Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain. METHODS: In a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating concentrations of 97 lipid metabolites (acylcarnitines, glycerophospholipids and sphingolipids) and colorectal cancer risk. Circulating lipids were measured using targeted mass spectrometry in 1591 incident colorectal cancer cases (55% women) and 1591 matched controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between concentrations of individual lipid metabolites and metabolite patterns with colorectal cancer risk. FINDINGS: Of the 97 assayed lipids, 24 were inversely associated (nominally p < 0.05) with colorectal cancer risk. Hydroxysphingomyelin (SM (OH)) C22:2 (OR(per doubling) 0.60, 95% CI 0.47–0.77) and acylakyl-phosphatidylcholine (PC ae) C34:3 (OR(per doubling) 0.71, 95% CI 0.59–0.87) remained associated after multiple comparisons correction. These associations were unaltered after excluding the first 5 years of follow-up after blood collection and were consistent according to sex, age at diagnosis, BMI, and colorectal subsite. Two lipid patterns, one including 26 phosphatidylcholines and all sphingolipids, and another 30... Continued on ES/IODE ➡️ https://etcse.fr/mZSW ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

🔎 📰 Esteban Gurzov's publication hereunder is linked to his research activity in his Signal Transduction & Metabolism Laboratory, which aims to understand how different cell types control signalling pathways in the context of metabolic disorders such as obesity, diabetes and liver cancer. 💉 His research activity is the subject of several patented inventions, including the following technology "𝐏𝐫𝐨𝐭𝐞𝐢𝐧 𝐓𝐲𝐫𝐨𝐬𝐢𝐧𝐞 𝐏𝐡𝐨𝐬𝐩𝐡𝐚𝐭𝐚𝐬𝐞𝐬-𝐦𝐞𝐝𝐢𝐚𝐭𝐞𝐝 𝐩𝐫𝐨𝐠𝐧𝐨𝐬𝐢𝐬 𝐨𝐟 𝐨𝐛𝐞𝐬𝐢𝐭𝐲-𝐢𝐧𝐝𝐮𝐜𝐞𝐝 𝐡𝐞𝐩𝐚𝐭𝐨𝐜𝐞𝐥𝐥𝐮𝐥𝐚𝐫 𝐜𝐚𝐫𝐜𝐢𝐧𝐨𝐦𝐚" 👉 https://lnkd.in/ej7XQtp3 #obesity #LiverCancer #diabetes

🔍 Exploring Adiposity, Protein Biomarkers, and CVD Risk 🔍 📄 Associations of Adiposity, Circulating Protein Biomarkers, and Risk of Major Vascular Diseases 👨🔬 Authors: Yuanjie Pang, Christiana Kartsonaki, Jun Lv, Zammy Fairhurst-Hunter, Iona Y Millwood, Canqing YU, Yu Guo, Yiping Chen, Zheng Bian, Ling Yang, Junshi Chen, Robert Clarke, Robin G Walters, Michael V Holmes, MD PhD, Liming Li, Zhengming Chen 🎓 #CME Credit: 1.0 Study Highlights: Objective: To examine the associations of adiposity with circulating protein biomarkers and their links to incident cardiovascular disease (CVD). Methodology: Analysis of 628 participants from the China Kadoorie Biobank, using linear regression and Mendelian randomization. Key Findings: BMI is linked to various protein biomarkers, some of which are associated with increased CVD risk, such as Interleukin-6 and Hepatocyte Growth Factor. This research underscores the intricate relationship between obesity, biomarkers, and cardiovascular health, paving the way for future studies to validate these findings and explore therapeutic interventions. Read the full article and earn CME credit here: https://lnkd.in/d8iWhsas #PhysicianInsights #MedicalResearch #CardiovascularHealth #ObesityResearch #CME #MedicalPractice #DoctorsUpdate

A recent study published on Nature.com examines the impact of dietary elements on immunotherapy in cancer treatment. It highlights the potential for diet and nutritional factors to enhance treatment effectiveness and reduce cancer-related morbidity and mortality through optimizing immune responses: https://lnkd.in/etSJRwvG #Immunotherapy #CancerTreatment #Oncology . . . https://lnkd.in/etSJRwvG