obesity and liver cancer

Obesity and related metabolic disorders have become globally prevalent posing a challenge for the chronically damaged liver and predisposing the development and progression of cancer. The rising phenomenon of "obesity epidemic" may provide means for understanding why liver cancer is one of the few malignancies with rising incidence in developed countries over the last decades. Non-alcoholic fatty liver disease associated with obesity, insulin resistance, and type 2 diabetes is an increasingly recognized trigger for liver cancer in Western populations characterized by low prevalence of established risk factors for liver cancer such as viral hepatitis and hepatotoxin exposure. Accumulating evidence has established an association between higher body mass index as an indicator of general obesity and higher risk of primary liver cancer. The associations are stronger in men, in patients with underlying liver disease and in white ethnic groups. Abdominal obesity, weight gain in adult life and metabolic factors related to visceral fat accumulation were also suggested as important risk factors for liver cancer; however, more studies are needed to evaluate these associations. The association of obesity and metabolic parameters with liver cancer survival remains controversial. It is unclear which exact mechanisms could provide links between obesity and liver cancer risk. Recent evidence has implicated several molecular pathways in obesity-associated liver cancer. These include insulin resistance leading to increased levels of insulin and insulin-like growth factors, chronic inflammation, adipose tissue remodeling, pro-inflammatory cytokine and adipokine secretion, and altered gut microbiota. These mechanisms coincide with inflammatory and metabolic processes occurring in non-alcoholic fatty liver disease predisposing cancer development and progression. In the context of the current evidence, better understanding of the role of obesity and related metabolic factors may help in improving current strategies for liver cancer prevention

Determinants and indicators of successful aging as a multidimensional outcome: a systematic review of longitudinal studies

BackgroundSuccessful aging (SA) has been coined as a term to describe the multidimensional aspects associated with achieving optimal combination of physical and mental health along with social well-being health, mental and social well-being at older age. In recent years there has been an increased interest in understanding the role of determinants of SA, such as demographic, biological, behavioral, psychological and social factors. To synthesize the recent evidence, we conducted a systematic review of longitudinal studies on a range of determinants and indicators of SA defined as a multidimensional outcome.MethodsA systematic search of PubMed, MEDLINE and Web of Science for finding eligible papers published between August 2016 and June 2023 was conducted following the Preferred Reporting Items for a Systematic Review and Meta-Analysis (PRISMA) guidelines. The review protocol was registered in PROSPERO International Prospective Register of Systematic Reviews (Registration number: CRD42021250200). The web-based automated screening tool–Rayyan–was used for title and abstract screening. The study quality was assessed using the Quality in Prognosis Studies (QUIPS) tool.ResultsA total of 3,191 records were initially identified using the predefined search strategy. Out of 289 articles selected for full text screening, 22 were found eligible and included in the review. A variety of factors have been explored in relation to SA, ranging from socio-demographic factors, nutrition, lifestyle, biological pathways, psychological health, and well-being. Overall, the results of recent studies have confirmed the role of metabolic health, adherence to healthy dietary patterns, such as the Mediterranean diet, physical activity, non-smoking, and higher socio-economic status as main factors associated with higher odds for SA. Emerging research highlights the role of psycho-social factors and early life health as determinants of SA.ConclusionIn summary, this review highlights the importance of healthy living and monitoring metabolic risk along with sustaining psychological well-being in adult life as major determinants of SA. Further methodological and research work on SA would pave the way toward development of adequate health promotion policies in aging societies.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021250200, CRD42021250200

Determinants and indicators of successful aging as a multidimensional outcome: a systematic review of longitudinal studies

Background: Successful aging (SA) has been coined as a term to describe the multidimensional aspects associated with achieving optimal combination of physical and mental health along with social well-being health, mental and social well-being at older age. In recent years there has been an increased interest in understanding the role of determinants of SA, such as demographic, biological, behavioral, psychological and social factors. To synthesize the recent evidence, we conducted a systematic review of longitudinal studies on a range of determinants and indicators of SA defined as a multidimensional outcome. Methods: A systematic search of PubMed, MEDLINE and Web of Science for finding eligible papers published between August 2016 and June 2023 was conducted following the Preferred Reporting Items for a Systematic Review and Meta-Analysis (PRISMA) guidelines. The review protocol was registered in PROSPERO International Prospective Register of Systematic Reviews (Registration number: CRD42021250200). The web-based automated screening tool–Rayyan–was used for title and abstract screening. The study quality was assessed using the Quality in Prognosis Studies (QUIPS) tool. Results: A total of 3,191 records were initially identified using the predefined search strategy. Out of 289 articles selected for full text screening, 22 were found eligible and included in the review. A variety of factors have been explored in relation to SA, ranging from socio-demographic factors, nutrition, lifestyle, biological pathways, psychological health, and well-being. Overall, the results of recent studies have confirmed the role of metabolic health, adherence to healthy dietary patterns, such as the Mediterranean diet, physical activity, non-smoking, and higher socio-economic status as main factors associated with higher odds for SA. Emerging research highlights the role of psycho-social factors and early life health as determinants of SA. Conclusion: In summary, this review highlights the importance of healthy living and monitoring metabolic risk along with sustaining psychological well-being in adult life as major determinants of SA. Further methodological and research work on SA would pave the way toward development of adequate health promotion policies in aging societies

Methodological utility of chemerin as a novel biomarker of immunity and metabolism

Chemerin is a recently discovered adipokine with inflammatory and metabolic actions relevant for chronic disease development. However, evidence from human research on the role of chemerin in chronic disease risk is still lacking. We assessed the reliability of plasma chemerin concentrations measured on two occasions over a 4-month period in 207 apparently healthy participants. In addition, we explored the cross-sectional associations between chemerin and inflammatory biomarkers using Spearman partial correlation and multivariable linear regression analyses. Intra-individual reproducibility of chemerin measurements was assessed by calculating intraclass correlation coefficients (ICCs) and exploration of Bland–Altman plots. Reliability analyses revealed good reproducibility of chemerin measurements (ICC: 0.72 (95%-CI 0.65, 0.78)). Visual inspection of Bland–Altman plots confirmed that the two time point measurements had a high level of agreement. In correlation analyses, chemerin was positively correlated with adiposity measures (body mass index and waist circumference). In addition, independent of adiposity measures, chemerin was correlated with the biomarkers C-reactive protein, fatty acid-binding protein 4 and progranulin (Rho-s ranging from 0.23 to 0.37). In multivariable linear regression analysis, a combination of correlated factors including body mass index, waist circumference, C-reactive protein, progranulin and fatty acid- binding protein-4 explained 28.0% of chemerin concentrations. These findings demonstrate methodological utility of chemerin concentrations in population- based research setting. Human studies are highly warranted in order to provide further insights into the role of chemerin as a biomarker linking immunity and metabolism in relation to chronic disease risk

A Reliability Study in a Cohort of 207 Apparently Healthy Participants

The reliability of single time point measurements of the novel adipokines retinol-binding protein 4 and omentin-1 in the blood has not been evaluated in large samples yet. The present study aimed to assess the amount of biological variation of these two adipokines within individuals. The study sample comprised 207 participants (124 women and 83 men) from Potsdam (Germany) and surrounding areas, with an average age of 56.5 years (SD 4.2). Blood samples were collected from each participant twice, approximately four months apart. Using enzyme linked immunosorbent assays, the concentrations of retinol- binding protein 4 and omentin-1 were determined in EDTA plasma. As indicators of reliability, intraclass correlation coefficients (ICCs) were calculated from the repeated biomarker measurements. The ICCs for repeated retinol- binding protein 4 and omentin-1 measurements were 0.77 (95% CI 0.71, 0.82) and 0.83 (95% CI 0.78, 0.87), respectively, indicating for both adipokines excellent reliability. ICCs were stable across strata according to sex, age, BMI, and blood pressure. Thus, for epidemiological studies it seems reasonable to rely on concentrations of retinol-binding protein 4 and omentin-1 in samples from a single time point if repeated measurements are not available

Heterogeneity of the Stearoyl-CoA desaturase-1 (SCD1) Gene and Metabolic Risk Factors in the EPIC-Potsdam Study

Background: Stearoyl-CoA desaturase-1 (SCD1) is an enzyme involved in lipid metabolism. In mice and humans its activity has been associated with traits of the metabolic syndrome, but also with the prevention of saturated fatty acids accumulation and subsequent inflammation, whereas for liver fat content inconsistent results have been reported. Thus, variants of the gene encoding SCD1 (SCD1) could potentially modify metabolic risk factors, but few human studies have addressed this question. Methods: In a sample of 2157 middle-aged men and women randomly drawn from the Potsdam cohort of the European Prospective Investigation into Cancer and Nutrition, we investigated the impact of 7 SCD1 tagging-single nucleotide polymorphisms (rs1502593, rs522951, rs11190480, rs3071, rs3793767, rs10883463 and rs508384) and 5 inferred haplotypes with frequency .5% describing 90.9% of the genotype combinations in our population, on triglycerides, body mass index (BMI), waist circumference (WC), glycated haemoglobin (HbA1c), high-sensitivity C-reactive protein (hs-CRP), gammaglutamyltransferase (GGT), alanine aminotransferase (ALT) and fetuin-A. Results: No significant associations between any of the SNPs or haplotypes and BMI, WC, fetuin-A and hs-CRP were observed. Associations of rs10883463 with triglycerides, GGT and HbA1c as well as of rs11190480 with ALT activity, were weak and became non-significant after multiple-testing correction. Also associations of the haplotype harbouring the minor allele of rs1502593 with HbA1c levels, the haplotype harbouring the minor alleles of rs11190480 and rs508384 with activity of ALT, and the haplotype harbouring the minor alleles of rs522951, rs10883463 and rs508384 with triglyceride and HbA1C levels and GGT activities did not withstand multiple-testing correction. Conclusion: These findings suggest that there are no associations between common variants of SCD1 or its inferred haplotypes and the investigated metabolic risk factors. However, given the results from animal models, heterogeneity of human SCD1 warrants further investigation, in particular with regard to rare variants

Functionality and Cell Senescence of CD4/ CD8-Selected CD20 CAR T Cells Manufactured Using the Automated CliniMACS Prodigy® Platform

Clinical studies using autologous CAR T cells have achieved spectacular remissions in refractory CD19+ B cell leukaemia, however some of the patient treatments with CAR T cells failed. Beside the heterogeneity of leukaemia, the distribution and senescence of the autologous cells from heavily pretreated patients might be further reasons for this. We performed six consecutive large-scale manufacturing processes for CD20 CAR T cells from healthy donor leukapheresis using the automated CliniMACS Prodigy® platform. Starting with a CD4/CD8-positive selection, a high purity of a median of 97% T cells with a median 65-fold cell expansion was achieved. Interestingly, the transduction rate was significantly higher for CD4+ compared to CD8+ T cells and reached in a median of 23%. CD20 CAR T cells showed a good specific IFN-γ secretion after cocultivation with CD20+ target cells which correlated with good cytotoxic activity. Most importantly, 3 out of 5 CAR T cell products showed an increase in telomere length during the manufacturing process, while telomere length remained consistent in one and decreased in another process. In conclusion, this shows for the first time that beside heterogeneity among healthy donors, CAR T cell products also differ regarding cell senescence, even for cells manufactured in a standardised automated process

Устойчивост на селското стопанство в България

This paper gives answer to topical and debated research and practical questions at the current stage of development of Bulgarian agriculture - „what is sustainability of agriculture", „how to assess sustainability of agricultural in the conditions of EU CAP implementation in the country“, and „which are critical factors for improvement of socio-economic and environmental sustainability in the sector“. Evolution of the „concept“ of agrarian sustainability and the major approached for its assessment are discussed More precise definition of sustainability of Bulgarian agriculture is suggested and the requirements for the system of its assessment are characterised. For the first time a new „governance“ pillar of agrarian sustainability is included along with the universally accepted economic, social and environmental pillars (aspects). Practically applicable for the specific conditions of Bulgarian agriculture holistic framework for assessing sustainability level of agrarian systems of different types (sector, sub-sector, region, ecosystem, agricultural farm) is suggested. The later included 25 principles, 66 criteria, and 163 indicators and reference values for assessing integral, governance, economic, social and environmental sustainability as well as approach for their calculation, integration and interpretation. Approbation of the elaborated framework in assessment of agrarian sustainability at various levels (national, sub-sector, region, (agro)ecosystem, and farm) is made on the base of official statistical, etc, information and original farm surveys. Critical factors for improving sustainability of Bulgarian agriculture are identified, and recommendation made for amelioration of research and assessment practices, public policies and farming strategies for sustainable development. Website of the project: https://zem.alle.b

Устойчивост на селското стопанство в България

This paper gives answer to topical and debated research and practical questions at the current stage of development of Bulgarian agriculture - „what is sustainability of agriculture", „how to assess sustainability of agricultural in the conditions of EU CAP implementation in the country“, and „which are critical factors for improvement of socio-economic and environmental sustainability in the sector“. Evolution of the „concept“ of agrarian sustainability and the major approached for its assessment are discussed More precise definition of sustainability of Bulgarian agriculture is suggested and the requirements for the system of its assessment are characterised. For the first time a new „governance“ pillar of agrarian sustainability is included along with the universally accepted economic, social and environmental pillars (aspects). Practically applicable for the specific conditions of Bulgarian agriculture holistic framework for assessing sustainability level of agrarian systems of different types (sector, sub-sector, region, ecosystem, agricultural farm) is suggested. The later included 25 principles, 66 criteria, and 163 indicators and reference values for assessing integral, governance, economic, social and environmental sustainability as well as approach for their calculation, integration and interpretation. Approbation of the elaborated framework in assessment of agrarian sustainability at various levels (national, sub-sector, region, (agro)ecosystem, and farm) is made on the base of official statistical, etc, information and original farm surveys. Critical factors for improving sustainability of Bulgarian agriculture are identified, and recommendation made for amelioration of research and assessment practices, public policies and farming strategies for sustainable development. Website of the project: https://zem.alle.b

Gallstones, Body Mass Index, C-Reactive Protein, and Gallbladder Cancer: Mendelian Randomization Analysis of Chilean and European Genotype Data

BACKGROUND AND AIMS: Gallbladder cancer (GBC) is a neglected disease with substantial geographical variability: Chile shows the highest incidence worldwide, while GBC is relatively rare in Europe. Here, we investigate the causal effects of risk factors considered in current GBC prevention programs as well as C-reactive protein (CRP) level as a marker of chronic inflammation. APPROACH AND RESULTS: We applied two-sample Mendelian randomization (MR) using publicly available data and our own data from a retrospective Chilean and a prospective European study. Causality was assessed by inverse variance weighted (IVW), MR-Egger regression, and weighted median estimates complemented with sensitivity analyses on potential heterogeneity and pleiotropy, two-step MR, and mediation analysis. We found evidence for a causal effect of gallstone disease on GBC risk in Chileans (P = 9 × 10−5) and Europeans (P = 9 × 10−5). A genetically elevated body mass index (BMI) increased GBC risk in Chileans (P = 0.03), while higher CRP concentrations increased GBC risk in Europeans (P = 4.1 × 10−6). European results suggest causal effects of BMI on gallstone disease (P = 0.008); public Chilean data were not, however, available to enable assessment of the mediation effects among causal GBC risk factors. CONCLUSIONS: Two risk factors considered in the current Chilean program for GBC prevention are causally linked to GBC risk: gallstones and BMI. For Europeans, BMI showed a causal effect on gallstone risk, which was itself causally linked to GBC risk. (Hepatology 2021;73:1783-1796).Fil: Barahona Ponce, Carol. Ruprecht Karls Universitat Heidelberg; Alemania. Universidad de Chile; ChileFil: Scherer, Dominique. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Brinster, Regina. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Boekstegers, Felix. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Marcelain, Katherine. Universidad de Chile; ChileFil: Gárate Calderón, Valentina. Ruprecht Karls Universitat Heidelberg; Alemania. Universidad de Chile; ChileFil: Müller, Bettina. Instituto Nacional del Cáncer; ChileFil: de Toro, Gonzalo. Hospital Puerto Montt; Chile. Universidad Austral de Chile; ChileFil: Retamales, Javier. Instituto Nacional del Cáncer; ChileFil: Barajas, Olga. Universidad de Chile; ChileFil: Ahumada, Monica. Universidad de Chile; ChileFil: Morales, Erik. Hospital Regional de Talca; Chile. Universidad Católica del Maule; ChileFil: Rojas, Armando. Universidad Católica del Maule; ChileFil: Sanhueza, Verónica. Hospital Padre Hurtado; ChileFil: Loader, Denisse. Hospital Padre Hurtado; ChileFil: Rivera, María Teresa. Hospital del Salvador; ChileFil: Gutiérrez, Lorena. Hospital San Juan de Dios; ChileFil: Bernal, Giuliano. Universidad Católica del Norte; ChileFil: Ortega, Alejandro. Hospital Regional; ChileFil: Montalvo, Domingo. Hospital Regional Juan Noé Crevani; ChileFil: Portiño, Sergio. Universidad de Chile; ChileFil: Bertrán, Maria Enriqueta. Ministerio de Salud; ChileFil: Gabler, Fernando. Universidad de Santiago de Chile. Hospital Clinico San Borja Arriaran; ChileFil: Spencer, Loreto. Hospital Regional Guillermo Grant Benavente; ChileFil: Olloquequi, Jordi. Universidad Autónoma de Chile; ChileFil: Fischer, Christine. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Jenab, Mazda. International Agency For Research On Cancer; AlemaniaFil: Aleksandrova, Krasimira. German Institute Of Human Nutrition; AlemaniaFil: Katzke, Verena. German Cancer Research Center; AlemaniaFil: Gonzalez-Jose, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentin