Explore the vast range of titles available.

Curcumin, a polyphenol extracted from Curcuma longa in 1815, has gained attention from scientists worldwide for its biological activities (e.g., antioxidant, anti-inflammatory, antimicrobial, antiviral), among which its anticancer potential has been the most described and still remains under investigation. The present review focuses on the cell signaling pathways involved in cancer development and proliferation, and which are targeted by curcumin. Curcumin has been reported to modulate growth factors, enzymes, transcription factors, kinase, inflammatory cytokines, and proapoptotic (by upregulation) and antiapoptotic (by downregulation) proteins. This polyphenol compound, alone or combined with other agents, could represent an effective drug for cancer therapy.

The p53 transcription factor plays a critical role in cellular responses to stress. Its activation in response to DNA damage leads to cell growth arrest, allowing for DNA repair, or directs cellular senescence or apoptosis, thereby maintaining genome integrity. Senescence is a permanent cell-cycle arrest that has a crucial role in aging, and it also represents a robust physiological antitumor response, which counteracts oncogenic insults. In addition, senescent cells can also negatively impact the surrounding tissue microenvironment and the neighboring cells by secreting pro-inflammatory cytokines, ultimately triggering tissue dysfunction and/or unfavorable outcomes. This review focuses on the characteristics of senescence and on the recent advances in the contribution of p53 to cellular senescence. Moreover, we also discuss the p53-mediated regulation of several pathophysiological microenvironments that could be associated with senescence and its development.

Key Points Obesity is a pathological enlargement of the adipose organ; this process involves the whitening and functional impairment of thermogenic brown adipose tissue and the inflammation of hypertrophied adipose depots. The occurrence of these two phenomena at visceral fat sites causes the most dangerous outcomes of obesity, including type 2 diabetes mellitus, dyslipidaemia, non-alcoholic fatty liver disease, cardiovascular disease and even some cancers. Visceral adipocytes are particularly vulnerable to lipid overload, possibly because of their developmental route and the reduced size at which they die, thereby promoting inflammation. Human and rodent visceral adipocytes exhibit remarkable cell plasticity. Indeed, such cells are particularly prone to re-convert into metabolically healthy, energy-dissipating adipocytes. Molecular targets and pathways that are involved in white-to-brown visceral adipocyte transdifferentiation are potential novel targets of anti-obesity drugs. Even the early steps of white-to-brown adipocyte transdifferentiation, which include adipocyte size reduction and mitochondriogenesis, could promote a healthy adipose phenotype and achieve effective therapeutic outcomes. Current therapies for obesity have limited efficacy and may be associated with substantial adverse effects. Cinti and colleagues discuss the conversion of white fat to brown, thermogenic fat as a potential strategy to curb obesity. Adipocyte conversion could be particularly important in the visceral compartment, as fat in this region is associated with morbidity but is also particularly prone to transdifferentiation. New therapeutic and preventative strategies are needed to address the growing obesity epidemic. In animal models, brown adipose tissue activation and the associated heat produced contribute to countering obesity and the accompanying metabolic abnormalities. Adult humans also have functional brown fat. Here, we present and discuss the concepts of murine and human white adipose tissue plasticity and the transdifferentiation of white adipocytes into brown adipocytes. Human visceral adipocytes — which are crucial contributors to the burden of obesity and its complications — are particularly susceptible to such transdifferentiation. Therefore, we propose that this process should be a focus of anti-obesity research. Approved drugs that have browning properties as well as future drugs that target molecular pathways involved in white-to-brown visceral adipocyte transdifferentiation may provide new avenues for obesity therapy.

The p53 protein is a transcription factor known as the \"guardian of the genome\" because of its critical function in preserving genomic integrity. The TP53 gene is mutated in approximately half of all human malignancies, including those of the breast, colon, lung, liver, prostate, bladder, and skin. When DNA damage occurs, the TP53 gene on human chromosome 17 stops the cell cycle. If p53 protein is mutated, the cell cycle is unrestricted and the damaged DNA is replicated, resulting in uncontrolled cell proliferation and cancer tumours. Tumor-associated p53 mutations are usually associated with phenotypes distinct from those caused by the loss of the tumor-suppressing function exerted by wild-type p53protein. Many of these mutant p53 proteins have oncogenic characteristics, and therefore modulate the ability of cancer cells to proliferate, escape apoptosis, invade and metastasize. Because p53 deficiency is so common in human cancer, this protein is an excellent option for cancer treatment. In this review, we will discuss some of the molecular pathways by which mutant p53 proteins might perform their oncogenic activities, as well as prospective treatment methods based on restoring tumor suppressive p53 functions.

Current treatment for acute myeloid leukemia (AML) is less than optimal, but increased understanding of disease pathobiology and genomics has led to clinical investigation of novel targeted therapies and rational combinations. Targeting the cyclin-dependent kinase 9 (CDK9) pathway, which is dysregulated in AML, is an attractive approach. Inhibition of CDK9 leads to downregulation of cell survival genes regulated by super enhancers such as MCL-1 , MYC , and cyclin D1. As CDK9 inhibitors are nonselective, predictive biomarkers that may help identify patients most likely to respond to CDK9 inhibitors are now being utilized, with the goal of improving efficacy and safety.

Leptin, produced and secreted by white adipose tissue in tight relationship with adipose mass, informs the brain about the status of the energy stores serving as the main peripheral signal for energy balance regulation through interaction with a multitude of highly interconnected neuronal populations. Most obese patients display resistance to the anorectic effect of the hormone. The present review unravels the multiple levels of complexity that trigger hypothalamic response to leptin with the objective of highlighting those critical hubs that, mainly in the hypothalamic arcuate nucleus, may undergo obesity-induced alterations and create an obstacle to leptin action. Several mechanisms underlying leptin resistance have been proposed, possibly representing useful targets to empower leptin effects. Among these, a special focus is herein dedicated to detail how leptin gains access into the brain and how neuronal plasticity may interfere with leptin function.

[...]they (schizophrenia and cancer) share several risk factors, such as pollution, smoking (either nicotine or cannabis), migrant status, adverse life events, bullying, physical abuse and child maltreatment, and alcohol consumption. Nongenetic factors, such as infections, childhood maltreatment, cannabis use, alcohol, smoking, and air, water, and soil pollution, can make the genome more “instable,” modifying its structure. [...]the environment would “trigger” complex and specific cellular pathways that, through epigenetic modification, can become transmissible from one generation to another [8]. [...]environmental pollution must be necessarily addressed, as in fact it could represent a real possibility of reducing the onset of cancer in conjunction with enhanced prevention.

In 2014, the International Agency for Research on Cancer (IARC) classified the first type of carbon nanotubes (CNTs) as possibly carcinogenic to humans, while in the case of other CNTs, it was not possible to ascertain their toxicity due to lack of evidence. Moreover, the physicochemical heterogeneity of this group of substances hamper any generalization on their toxicity. Here, we review the recent relevant toxicity studies produced after the IARC meeting in 2014 on an homogeneous group of CNTs, highlighting the molecular alterations that are relevant for the onset of mesothelioma. Methods: The literature was searched on PubMed and Web of Science for the period 2015–2020, using different combinations keywords. Only data on normal cells of the respiratory system after exposure to fully characterized CNTs for their physico-chemical characteristics were included. Recent studies indicate that CNTs induce a sustained inflammatory response, oxidative stress, fibrosis and histological alterations. The development of mesothelial hyperplasia, mesothelioma, and lungs tumors have been also described in vivo. The data support a strong inflammatory potential of CNTs, similar to that of asbestos, and provide evidence that CNTs exposure led to molecular alterations known to have a key role in mesothelioma onset. These evidences call for an urgent improvement of studies on exposed human populations and adequate systems for monitoring the health of workers exposed to this putative carcinogen.

Metabolic flexibility describes the ability of cells to respond or adapt its metabolism to support and enable rapid proliferation, continuous growth, and survival in hostile conditions. This dynamic character of the cellular metabolic network appears enhanced in cancer cells, in order to increase the adaptive phenotype and to maintain both viability and uncontrolled proliferation. Cancer cells can reprogram their metabolism to satisfy the energy as well as the biosynthetic intermediate request and to preserve their integrity from the harsh and hypoxic environment. Although several studies now recognize these reprogrammed activities as hallmarks of cancer, it remains unclear which are the pathways involved in regulating metabolic plasticity. Recent findings have suggested that carnitine system (CS) could be considered as a gridlock to finely trigger the metabolic flexibility of cancer cells. Indeed, the components of this system are involved in the bi-directional transport of acyl moieties from cytosol to mitochondria and vice versa, thus playing a fundamental role in tuning the switch between the glucose and fatty acid metabolism. Therefore, the CS regulation, at both enzymatic and epigenetic levels, plays a pivotal role in tumors, suggesting new druggable pathways for prevention and treatment of human cancer.

White adipose tissue, once regarded as morphologically and functionally bland, is now recognized to be dynamic, plastic and heterogenous, and is involved in a wide array of biological processes including energy homeostasis, glucose and lipid handling, blood pressure control and host defence 1 . High-fat feeding and other metabolic stressors cause marked changes in adipose morphology, physiology and cellular composition 1 , and alterations in adiposity are associated with insulin resistance, dyslipidemia and type 2 diabetes 2 . Here we provide detailed cellular atlases of human and mouse subcutaneous and visceral white fat at single-cell resolution across a range of body weight. We identify subpopulations of adipocytes, adipose stem and progenitor cells, vascular and immune cells and demonstrate commonalities and differences across species and dietary conditions. We link specific cell types to increased risk of metabolic disease and provide an initial blueprint for a comprehensive set of interactions between individual cell types in the adipose niche in leanness and obesity. These data comprise an extensive resource for the exploration of genes, traits and cell types in the function of white adipose tissue across species, depots and nutritional conditions. A single-cell atlas of white adipose tissue from mouse and human reveals diverse cell types and similarities and differences across species and dietary conditions.