Viewpoint

Stress management by benzodiazepines in septic shock and critical illness: mechanistic and clinical evidence supporting alternative sedative strategies

Flavia Lambertucci1, David Skurnik2,3, Damien Roux4,5, Laurence Arbibe6, Lucillia Bezu1,7,8, Isabelle Martins1 and Guido Kroemer1,7,9

For full text please see pdf.

The missing hallmark of health: psychosocial adaptation

Carlos López-Otín1,2,3 and Guido Kroemer1,4,5

INTRODUCTION The comprehension of health –defined in a positive fashion rather than as the absence of disease–requires a theory. We recently launched the bases of such a health theory by

Impact of microbiota on breast cancer hormone therapy

Safae Terrisse1, Laurence Zitvogel2-5 and Guido Kroemer6-8

Recent observations indicate that the pathogenesis and prognosis of hormone-receptor breast cancer is not only dictated by the properties of the malignant cells but also by immune and microbial parameters. Thus, the immunosurveillance system retards the development of hormone-positive breast cancer and contributes to the therapeutic efficacy of estrogen receptor antagonists and aromatase inhibitors. Moreover, the anticancer immune response is profoundly modulated by the local and intestinal microbiota, which influences cancer cell-intrinsic signaling pathways, affects the composition and function of the immune infiltrate present in the tumor microenvironment and modulates the metabolism of estrogens. Indeed, specific bacteria in the gut produce enzymes that affect the enterohepatic cycle of estrogen metabolites, convert estrogens into androgens or generate estrogen-like molecules. The knowledge of these circuitries is in its infancy, calling for further in-depth analyses.

Poly(ADP-ribose) polymerase-1 and its ambiguous role in cellular life and death

Maria Castedo1,2, Antoine Lafarge1,2,3 and Guido Kroemer1,2,4

The deletion of the gene coding for poly(ADPribose) polymerase-1 (PARP1) or its pharmacological inhibition protects mice against cerebral ischemia and Parkinson’s disease. In sharp contrast, PARP1 inhibitors are in clinical use for the eradication of vulnerable cancer cells. It appears that excessive PARP1 activation is involved in a specific cell death pathway called parthanatos, while inhibition of PARP1 in cancer cells amplifies DNA damage to a lethal level. Hence, PARP1 plays a context-dependent role in cell fate decisions. In addition, it appears that PARP1 plays an ambiguous role in organismal aging.

Rethinking the bioavailability and cellular transport properties of S-adenosylmethionine

Yudong Sun1 and Jason W. Locasale2

S-adenosylmethionine (SAM) is a versatile metabolite that participates in a wide range of reactions such as methylation and transsulfuration. These capabilities allow SAM to influence cellular processes such as gene expression and redox balancing. The importance of SAM is highlighted by its widespread usage as an over-the-counter nutrient supplement and as an experimental reagent in molecular biology. The bioavailability and cellular transport properties of SAM, however, are often overlooked under these contexts, putting limits on SAM’s therapeutic potential and complicating the interpretation of experimental results. In this article, we examined the chemical stability and cellular permeability of SAM, proposed a schematic for indirect SAM transport across the mammalian plasma membrane, and lastly discussed the implications arising from such transport schematic.

Elevated plasma levels of the appetite-stimulator ACBP/DBI in fasting and obese subjects

Sijing Li1-3,#, Adrien Joseph1-3,#, Isabelle Martins1,2 and Guido Kroemer1,2,4-6

INTRODUCTION Acyl coenzyme A binding protein (ACBP), which in humans is encoded by the gene DBI (diazepam binding inhibitor), is a phylogenetically ancient protein that is ubiquitously expressed by all

Exploiting the circuit breaker cancer evolution model in human clear cell renal cell carcinoma

James J. Hsieh1 and Emily H. Cheng2,3,4

INTRODUCTION On average a human adult body encompasses fifty trillion cells (~5×1013) with a daily turnover of hundred billion cells (~1011) within which each contains two copies of ~three billion

Necroptosis, tumor necrosis and tumorigenesis

Zheng-gang Liu1 and Delong Jiao1

INTRODUCTION Cell death can happen through either an active, regulated process, known as programmed cell death, or a passive, uncontrolled course. Because of the dramatic morphological differences of these two

The targeting of tumor-associated macrophages by vaccination

Mads Hald Andersen1,2,3

Immune suppressive myeloid cells include a heterogenous population of cells that include tumor-associated macrophages (TAMs). TAMs are major players in inducing the immunosuppressive microenvironment associated with many tumors. These lesions

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