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Effets d’un effort physique sur l’irrigation sanguine d’une tumeur?

27/07/2016 | Etudes Anti-âge

 

Blood flow responses to mild-intensity exercise in ectopic vs. orthotopic prostate tumors; dependence upon host tissue hemodynamics and vascular reactivity
Emmanuel Garcia         Journal of Applied Physiology Published 1 July 2016 Vol. 121 no. 1, 15-24

Given the critical role of tumor O2 delivery in patient prognosis and the rise in preclinical exercise oncology studies, we investigated tumor and host tissue blood flow at rest and during exercise as well as vascular reactivity using a rat prostate cancer model grown in two transplantation sites. In male COP/CrCrl rats, blood flow (via radiolabeled microspheres) to prostate tumors [R3327-MatLyLu cells injected in the left flank (ectopic) or ventral prostate (orthotopic)] and host tissue was measured at rest and during a bout of mild-intensity exercise. α-Adrenergic vasoconstriction to norepinephrine (NE: 10−9 to 10−4 M) was determined in arterioles perforating the tumors and host tissue. To determine host tissue exercise hyperemia in healthy tissue, a sham-operated group was included.

Blood flow was lower at rest and during exercise in ectopic tumors and host tissue (subcutaneous adipose) vs. the orthotopic tumor and host tissue (prostate).

During exercise, blood flow to the ectopic tumor significantly decreased by 25 ± 5% (SE), whereas flow to the orthotopic tumor increased by 181 ± 30%.

Maximal vasoconstriction to NE was not different between arterioles from either tumor location. However, there was a significantly higher peak vasoconstriction to NE in subcutaneous adipose arterioles (92 ± 7%) vs. prostate arterioles (55 ± 7%). Establishment of the tumor did not alter host tissue blood flow from either location at rest or during exercise.

These data demonstrate that blood flow in tumors is dependent on host tissue hemodynamics and that the location of the tumor may critically affect how exercise impacts the tumor microenvironment and treatment outcomes.

Tout sur la 11-kéto-testostérone

24/07/2016 | Etudes sur les hormones

 

11-ketotestosterone is a major androgen produced in human gonads
Yoshitaka Imamichi     The Journal of Clinical Endocrinology & Metabolism First Published Online: July 18, 2016

11-ketotestosterone (11-KT) is a novel class of active androgen. However, the detail of its synthesis remains unknown for humans.
Objective: The objective of this study was to clarify the production and properties of 11-KT in human.

Design, Participants and Methods: Expression of CYP11B1 and HSD11B2 (key enzymes involved in the synthesis of 11-KT) were investigated in human gonads. The production of 11-KT was investigated in Leydig cells. Plasma concentrations of testosterone and 11-KT were measured in 10 women and 10 men of reproductive age. Investigation of its properties was performed using breast cancer-derived MCF-7 cells.

Results: CYP11B1 and HSD11B2 were detected in Leydig cells and theca cells. Leydig cells produced 11-KT, and relatively high levels of plasma 11-KT were measured in both men and women. There was no sexual dimorphism in the plasma levels of 11-KT, even though testosterone levels were more than 20-times higher in men than in women. It is noteworthy that the levels of testosterone and 11-KT were similar in women. In a luciferase reporter system, 11-KT activated human androgen receptor (AR)-mediated transactivation. Conversely, 11-KT did not activate estrogen receptor (ER)-mediated transactivation in aromatase-expressed MCF-7 cells, whereas testosterone did following conversion to estrogen. 11-KT did not affect the estrogen/ER-mediated cell proliferation of MCF-7 cells. Furthermore, it significantly inhibited cell proliferation when AR was transfected into MCF-7 cells.

Conclusions: The current study indicates that 11-KT is produced in the gonads and represents a major androgen in human. It can potentially serve as a non-aromatizable androgen.

Tout savoir sur l’humanine

23/07/2016 | Etudes sur les hormones

 

Humanin: Functional Interfaces with IGF-I
Growth Hormone & IGF Research Volume 29, August 2016, Pages 21–27       J. Xiao

Highlights
• Humanin is a new player in the regulation of the GH-IGF axis.
• IGFBP-3 interacts with humanin to influence both IGF-I and humanin bioavailability.
• Humanin is the first member of a novel class of peptides encoded within small open reading frames in the mitochondrial genome.
• Humanin has also been shown to have neuroprotective and cytoprotective effects.
• Humanin decreases circulating IGF-I levels in mouse studies, having a diet-restriction-mimetic effect.

Humanin is the first newly discovered peptide encoded in the mitochondrial genome in over three decades. It is the first member of a novel class of mitochondrial derived peptides. This small, 24 amino acid peptide was initially discovered to have neuroprotective effects and subsequent experiments have shown that it is beneficial in a diverse number of disease models including stroke, cardiovascular disease, and cancer. Over a decade ago, our lab found that humanin bound IGFBP-3 and more recent studies have found it to decrease circulating IGF-I levels. In turn, IGF-I also seems to regulate humanin levels and in this review, we cover the known interaction between humanin and IGF-I. Although the exact mechanism for how humanin and IGF-I regulate each other still needs to be elucidated, it is clear that humanin is a new player in IGF-I signaling.

L’ostéocalcine est une hormone anabolique pour les muscles

22/07/2016 | Etudes sur les hormones et Etudes Perte de poids et Etudes Anti-âge

 

Osteocalcin is necessary and sufficient to maintain muscle mass in older mice
Molecular Metabolism Available online 16 July 2016       Paula Mera

Highlights

• Osteocalcin is necessary to maintain muscle mass in older mice.
• Osteocalcin is sufficient to increase muscle mass in older mice.
• Osteocalcin promotes protein synthesis in myotubes.

A decrease in muscle protein turnover and therefore in muscle mass is a hallmark of aging. Because the circulating levels of the bone-derived hormone osteocalcin decline steeply during aging in mice, monkeys and humans we asked here whether this hormone might regulate muscle mass as mice age.

Methods
We examined muscle mass and strength in mice lacking osteocalcin (Ocn−/−) or its receptor in all cells (Gprc6a−/−) or specifically in myofibers (Gprc6aMck−/−) as well as in 9 month-old WT mice receiving exogenous osteocalcin for 28 days. We also examined protein synthesis in WT and Gprc6a−/− mouse myotubes treated with osteocalcin.

Results
We show that osteocalcin signaling in myofibers is necessary to maintain muscle mass in older mice in part because it promotes protein synthesis in myotubes without affecting protein breakdown. We further show that treatment with exogenous osteocalcin for 28 days is sufficient to increase muscle mass of 9-month-old WT mice.

Conclusion
This study uncovers that osteocalcin is necessary and sufficient to prevent age-related muscle loss in mice.

Tout savoir sur la prohibitine

21/07/2016 | Etudes Perte de poids et Etudes Anti-âge

 

Prohibitin in Adipose and Immune Functions
Trends in Endocrinology & Metabolism Volume 27, Issue 8, August 2016, Pages 531–541     Sudharsana R. Ande

Prohibitin (PHB) was discovered in a quest to find genes with antiproliferative functions. However, the attribute of PHB that is responsible for its antiproliferative function remains elusive. Meanwhile, recent studies have established PHB as a pleiotropic protein with roles in metabolism, immunity, and senescence. PHB has cell compartment-specific functions, acting as a scaffolding protein in mitochondria, an adaptor molecule in membrane signaling, and a transcriptional coregulator in the nucleus. However, it remains unclear whether different functions and locations of PHB are interrelated or independent from each other, or if PHB works in a tissue-specific manner. Here, we discuss new findings on the role of PHB in adipose–immune interaction and an unexpected role in sex differences in adipose and immune functions.

Trends
- Prohibitin (PHB) plays a role in sex differences in adipose and immune functions.
- PHB overexpression in adipose tissue results in obesity in both male and female mice but only males develop obesity-related metabolic dysregulation, steatohepatitis, and hepatocellular carcinoma (HCC) in a sex-specific manner.
- Overexpression of a mutant Y114F-PHB promotes obesity, adipose inflammation, and insulin resistance, as well as lymph node tumors in a male sex-specific manner but not steatohepatitis and HCC.
- Male mice overexpressing Y114F-PHB develop adult-onset type 1 diabetes when fed a high-fat diet instead of tumors.

Effets de l’apport calorique sur la follistatine

20/07/2016 | Etudes Perte de poids et Etudes Anti-âge

 

Circulating follistatin in relation to energy metabolism
Molecular and Cellular Endocrinology Volume 433, 15 September 2016, Pages 87–93       Jakob Schiøler Hansen

Highlights
• Circulating follistatin is increased in conditions associated with insulin resistance.
• The glucagon-to-insulin ratio has been identified to regulate circulating follistatin.
• The liver is a major source of the circulating follistatin in humans.
• This implies that circulating follistatin is related to energy metabolism.
• These observations elucidate why plasma follistatin is associated with insulin resistance.

Recently, substantial evidence has emerged that the liver contributes significantly to the circulating levels of follistatin and that circulating follistatin is tightly regulated by the glucagon-to-insulin ratio. Both observations are based on investigations of healthy subjects. These novel findings challenge the present view of circulating follistatin in human physiology, being that circulating follistatin is a result of spill-over from para/autocrine actions in various tissues and cells. Follistatin as a liver-derived protein under the regulation of glucagon-to-insulin ratio suggests a relation to energy metabolism. In this narrative review, we attempt to reconcile the existing findings on circulating follistatin with the novel concept that circulating follistatin is a liver-derived molecule regulated by the glucagon-to-insulin ratio. The picture emerging is that conditions associated with elevated levels of circulating follistatin have a metabolic denominator with decreased insulin sensitivity and/or hyperglucagoneimia.

Propriétés anti-grippe de l’éphédra sans éphédrine

10/07/2016 | Etudes Compléments alimentaires et Etudes Perte de poids et Etudes Anti-âge

 

Ephedrine alkaloids-free Ephedra Herb extract: a safer alternative to ephedra with comparable analgesic, anticancer, and anti-influenza activities
Journal of Natural Medicines July 2016, Volume 70, Issue 3, pp 571–583       Sumiko Hyug

It is generally accepted that the primary pharmacological activities and adverse effects of Ephedra Herb are caused by ephedrine alkaloids. Interestingly, our research shows that Ephedra Herb also has ephedrine alkaloid-independent pharmacological actions, such as c-MET inhibitory activity. This study describes the preparation of an ephedrine alkaloids-free Ephedra Herb extract (EFE) by ion-exchange column chromatography, as well as in vitro and in vivo evaluation of its pharmacological actions and toxicity. We confirmed that EFE suppressed hepatocyte growth factor (HGF)-induced cancer cell motility by preventing both HGF-induced phosphorylation of c-Met and its tyrosine kinase activity. We also investigated the analgesic effect of EFE. Although the analgesic effect of Ephedra Herb has traditionally been attributed to pseudoephedrine, oral administration of EFE reduced formalin-induced pain in a dose-dependent manner in mice. Furthermore, we confirmed the anti-influenza virus activity of EFE by showing inhibition of MDCK cell infection in a concentration-dependent manner. All assessments of toxicity, even after repeated oral administration, suggest that EFE would be a safer alternative to Ephedra Herb.

The findings described here suggest that EFE has c-Met inhibitory action, analgesic effect, and anti-influenza activity, and that it is safer than Ephedra Herb extract itself. Therefore, EFE could be a useful pharmacological agent.

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