Exploring the interplay between stress mediators and skin microbiota in shaping age-related hallmarks: A review.

Psychological stress is a major contributing factor to several health problems (e.g., depression, cardiovascular disease). Around 35 % of the world's population suffers from it, including younger generations. Physiologically, stress manifests through neuroendocrine pathways (Hypothalamic-Pituitary-Adrenal (HPA) axis and Sympathetic-Adrenal-Medullary (SAM) system) which culminate in the production of stress mediators like cortisol, epinephrine and norepinephrine. Stress and its mediators have been associated to body aging, through molecular mechanisms such as telomere attrition, mitochondrial dysfunction, cellular senescence, chronic inflammation, and dysbiosis, among others. Regarding its impact in the skin, stress impacts its structural integrity and physiological function. Despite this review focusing on several hallmarks of aging, emphasis was placed on skin microbiota dysbiosis. In this line, several studies, comprising different age groups, demographic contexts and body sites, have reported skin microbiota alterations associated with aging, and some effects of stress mediators on skin microbiota have also been reviewed in this paper. From a different perspective, since it is not a "traditional" stress mediator, oxytocin, a cortisol antagonist, has been related to glucorticoids inhibition and to display positive effects on cellular aging. This hormone dysregulation has been associated to psychological issues such as depression, whereas its upregulation has been linked to positive social interaction.

Maternal diet, C-reactive protein, and the outcome of pregnancy.

OBJECTIVE: To examine the association of high-sensitivity C-reactive protein (hsCRP), a systemic biomarker for the inflammatory process at entry to care, with pregnancy-induced hypertension/preeclampsia, adverse outcomes of pregnancy, and the maternal diet. DESIGN: Random sample (N = 520) with normal glucose tolerance from a large prospective cohort study of urban, low income, minority gravidae. RESULTS: During pregnancy, the highest tertile of hsCRP (range, 7.06-137.41 mg/L) was associated with significantly increased risks for early preterm delivery (<34 weeks). However, after stratification by maternal pregravid body mass index (BMI), risk for early preterm delivery <34 weeks (adjusted odds ratios [AOR] = 3.58, 95% confidence interval [CI] = 1.05-12.27), and pregnancy-induced hypertension (AOR = 2.66, 95% CI = 1.03-6.86) including preeclampsia (AOR = 2.72, 95% CI = 1.08-6.85) was shown to be specific to lean women (BMI <25) with high hsCRP. Increased hsCRP was unrelated to risk among overweight and obese gravidae. We found high hsCRP to be associated with diet. After stratification by BMI, dietary differences (higher intakes of protein and cholesterol with a lower intake of carbohydrate and a higher entry dietary glycemic index) were associated with increased hsCRP only among lean gravidae and not among those who were overweight or obese. CONCLUSIONS: High hsCRP is a diet-related biomarker for serious complications and poor outcome in lean women with normal glucose tolerance.

Src activates Abl to augment Robo1 expression in order to promote tumor cell migration.

Cell migration is an essential step in cancer invasion and metastasis. A number of orchestrated cellular events involving tyrosine kinases and signaling receptors enable cancer cells to dislodge from primary tumors and colonize elsewhere in the body. For example, activation of the Src and Abl kinases can mediate events that promote tumor cell migration. Also, activation of the Robo1 receptor can induce tumor cell migration. However, while the importance of Src, Abl, and Robo1 in cell migration have been demonstrated, molecular mechanisms by which they collectively influence cell migration have not been clearly elucidated. In addition, little is known about mechanisms that control Robo1 expression. We report here that Src activates Abl to stabilize Robo1 in order to promote cell migration. Inhibition of Abl kinase activity by siRNA or kinase blockers decreased Robo1 protein levels and suppressed the migration of transformed cells. We also provide evidence that Robo1 utilizes Cdc42 and Rac1 GTPases to induce cell migration. In addition, inhibition of Robo1 signaling can suppress transformed cell migration in the face of robust Src and Abl kinase activity. Therefore, inhibitors of Src, Abl, Robo1 and small GTPases may target a coordinated pathway required for tumor cell migration.

SRC utilizes Cas to block gap junctional communication mediated by connexin43.

The Src tyrosine kinase phosphorylates Cas (Crk-associated substrate) to confer anchorage independence and invasive growth potential to transformed cells. Gap junctional communication is often lower between aggressive tumor cells compared with normal or benign precursors. The gap junction protein connexin43 (Cx43) is a tumor suppressor that can inhibit tumor cell growth. Src can phosphorylate Cx43 to block gap junctional communication between transformed cells. However, mechanisms by which this event actually closes intercellular channels have not been clearly defined. Here, we report that Src and Cas associate with each other at intercellular junctions. In addition, Cas is required for Src to reduce dye transfer and electrical coupling between cells expressing Cx43. Thus, Src utilizes Cas to inhibit gap junctional communication mediated by Cx43. This finding introduces a novel role of the Cas focal adhesion linker protein in the gap junction complex. This observation may help explain how gap junctional communication can be suppressed between malignant and metastatic tumor cells.