Links between cardiovascular disease and osteoporosis in postmenopausal women: serum lipids or atherosclerosis per se?

INTRODUCTION AND HYPOTHESIS: Epidemiological observations suggest links between osteoporosis and risk of acute cardiovascular events and vice versa. Whether the two clinical conditions are linked by common pathogenic factors or atherosclerosis per se remains incompletely understood. We investigated whether serum lipids and polymorphism in the ApoE gene modifying serum lipids could be a biological linkage. METHODS: This was an observational study including 1176 elderly women 60–85 years old. Women were genotyped for epsilon (ɛ) allelic variants of the ApoE gene, and data concerning serum lipids (total cholesterol, triglycerides, HDL-C, LDL-C, apoA1, ApoB, Lp(a)), hip and spine BMD, aorta calcification (AC), radiographic vertebral fracture and self-reported wrist and hip fractures, cardiovascular events together with a wide array of demographic and lifestyle characteristics were collected. RESULTS: Presence of the ApoE ɛ4 allele had a significant impact on serum lipid profile, yet no association with spine/hip BMD or AC could be established. In multiple regression models, apoA1 was a significant independent contributor to the variation in AC. However, none of the lipid components were independent contributors to the variation in spine or hip BMD. When comparing the women with or without vertebral fractures, serum triglycerides showed significant differences. This finding was however not applicable to hip or wrist fractures. After adjustment for age, severe AC score (≥6) and/or manifest cardiovascular disease increased the risk of hip but not vertebral or wrist fractures. CONCLUSION: The contribution of serum lipids to the modulators of BMD does not seem to be direct but rather indirect via promotion of atherosclerosis, which in turn can affect bone metabolism locally, especially when skeletal sites supplied by end-arteries are concerned. Further studies are needed to explore the genetic or environmental risk factors underlying the association of low triglyceride levels to vertebral fractures

A multidisciplinary consensus on the morphological and functional responses to immunotherapy treatment

The implementation of immunotherapy has radically changed the treatment of oncological patients. Currently, immunotherapy is indicated in the treatment of patients with head and neck tumors, melanoma, lung cancer, bladder tumors, colon cancer, cervical cancer, breast cancer, Merkel cell carcinoma, liver cancer, leukemia and lymphomas. However, its efficacy is restricted to a limited number of cases. The challenge is, therefore, to identify which subset of patients would benefit from immunotherapy. To this end, the establishment of immunotherapy response criteria and predictive and prognostic biomarkers is of paramount interest. In this report, a group of experts of the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) provide an up-to-date review and a consensus guide on these issues

Tankyrase inhibition sensitizes melanoma to PD-1 immune checkpoint blockade in syngeneic mouse models

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Modulation of hepatic inflammation and energy-sensing pathways in the rat liver by high-fructose diet and chronic stress

Purpose High-fructose consumption and chronic stress are both associated with metabolic inflammation and insulin resistance. Recently, disturbed activity of energy sensor AMP-activated protein kinase (AMPK) was recognized as mediator between nutrient-induced stress and inflammation. Thus, we analyzed the effects of high-fructose diet, alone or in combination with chronic stress, on glucose homeostasis, inflammation and expression of energy sensing proteins in the rat liver. Methods In male Wistar rats exposed to 9-week 20% fructose diet and/or 4-week chronic unpredictable stress we measured plasma and hepatic corticosterone level, indicators of glucose homeostasis and lipid metabolism, hepatic inflammation (pro- and anti-inflammatory cytokine levels, Toll-like receptor 4, NLRP3, activation of NF kappa B, JNK and ERK pathways) and levels of energy-sensing proteins AMPK, SIRT1 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha). Results High-fructose diet led to glucose intolerance, activation of NF kappa B and JNK pathways and increased intrahepatic IL-1 beta, TNF alpha and inhibitory phosphorylation of insulin receptor substrate 1 on Ser(307). It also decreased phospho-AMPK/AMPK ratio and increased SIRT1 expression. Stress alone increased plasma and hepatic corticosterone but did not influence glucose tolerance, nor hepatic inflammatory or energy-sensing proteins. After the combined treatment, hepatic corticosterone was increased, glucose tolerance remained preserved, while hepatic inflammation was partially prevented despite decreased AMPK activity. Conclusion High-fructose diet resulted in glucose intolerance, hepatic inflammation, decreased AMPK activity and reduced insulin sensitivity. Chronic stress alone did not exert such effects, but when applied together with high-fructose diet it could partially prevent fructose-induced inflammation, presumably due to increased hepatic glucocorticoids

Climate change and freshwater zooplankton: what does it boil down to?

Recently, major advances in the climate–zooplankton interface have been made some of which appeared to receive much attention in a broader audience of ecologists as well. In contrast to the marine realm, however, we still lack a more holistic summary of recent knowledge in freshwater. We discuss climate change-related variation in physical and biological attributes of lakes and running waters, high-order ecological functions, and subsequent alteration in zooplankton abundance, phenology, distribution, body size, community structure, life history parameters, and behavior by focusing on community level responses. The adequacy of large-scale climatic indices in ecology has received considerable support and provided a framework for the interpretation of community and species level responses in freshwater zooplankton. Modeling perspectives deserve particular consideration, since this promising stream of ecology is of particular applicability in climate change research owing to the inherently predictive nature of this field. In the future, ecologists should expand their research on species beyond daphnids, should address questions as to how different intrinsic and extrinsic drivers interact, should move beyond correlative approaches toward more mechanistic explanations, and last but not least, should facilitate transfer of biological data both across space and time

Targeting adipose tissue

Two different types of adipose tissues can be found in humans enabling them to respond to starvation and cold: white adipose tissue (WAT) is generally known and stores excess energy in the form of triacylglycerol (TG), insulates against cold, and serves as a mechanical cushion. Brown adipose tissue (BAT) helps newborns to cope with cold. BAT has the capacity to uncouple the mitochondrial respiratory chain, thereby generating heat rather than adenosine triphosphate (ATP). The previously widely held view was that BAT disappears rapidly after birth and is no longer present in adult humans. Using positron emission tomography (PET), however, it was recently shown that metabolically active BAT occurs in defined regions and scattered in WAT of the adult and possibly has an influence on whole-body energy homeostasis. In obese individuals adipose tissue is at the center of metabolic syndrome. Targeting of WAT by thiazolidinediones (TZDs), activators of peroxisome proliferator-activated receptor γ (PPARγ) a ‘master’ regulator of fat cell biology, is a current therapy for the treatment of type 2 diabetes. Since its unique capacity to increase energy consumption of the body and to dissipate surplus energy as heat, BAT offers new perspectives as a therapeutic target for the treatment of obesity and associated diseases such as type 2 diabetes and metabolic syndrome. Recent discoveries of new signaling pathways of BAT development give rise to new therapeutic possibilities in order to influence BAT content and activity