Dysregulation of endoplasmic reticulum stress response in skin wounds in a streptozotocin-induced diabetes mouse model.

Dysfunction in key cellular organelles has been linked to diabetic complications. This study intended to investigate the alterations in the unfolded protein response (UPR), autophagy, and mitochondrial function, which are part of the endoplasmic reticulum (ER) stress response, in wound healing (WH) under diabetes conditions. WH mouse models were used to evaluate the UPR, autophagy, mitochondrial fusion, fission, and biogenesis as well as mitophagy in the skin of control and diabetic mice at baseline and 10 days after wounding.

Mitochondrial respiration in thoracic perivascular adipose tissue of diabetic mice.

Introduction: Thoracic perivascular adipose tissue (tPVAT) has a phenotype resembling brown AT. Dysfunctional tPVAT appears to be linked to vascular dysfunction.

Methods: We evaluated uncoupling protein 1 (UCP1) expression by Western blot, oxidative stress by measuring lipid peroxidation, the antioxidant capacity by HPLC and spectrophotometry, and mitochondrial respiration by high-resolution respirometry (HRR) in tPVAT, compared to inguinal white AT (iWAT), obtained from non-diabetic (NDM) and streptozocin-induced diabetic (STZ-DM) mice.

Altered mitochondrial epigenetics associated with subchronic doxorubicin cardiotoxicity.

Doxorubicin (DOX), a potent and broad-spectrum antineoplastic agent, causes an irreversible, cumulative and dose-dependent cardiomyopathy that ultimately leads to congestive heart failure. The mechanisms responsible for DOX cardiotoxicity remain poorly understood, but seem to involve mitochondrial dysfunction on several levels. Epigenetics may explain a portion of this effect.

Glucose and Lipid Dysmetabolism in a Rat Model of Prediabetes Induced by a High-Sucrose Diet.

Glucotoxicity and lipotoxicity are key features of type 2 diabetes mellitus, but their molecular nature during the early stages of the disease remains to be elucidated. We aimed to characterize glucose and lipid metabolism in insulin-target organs (liver, skeletal muscle, and white adipose tissue) in a rat model treated with a high-sucrose (HSu) diet. Two groups of 16-week-old male Wistar rats underwent a 9-week protocol: HSu diet ( = 10)-received 35% of sucrose in drinking water; Control ( = 12)-received vehicle (water).

Glucose uptake and lipid metabolism are impaired in epicardial adipose tissue from heart failure patients with or without diabetes.

Type 2 diabetes mellitus is a complex metabolic disease, and cardiovascular disease is a leading complication of diabetes. Epicardial adipose tissue surrounding the heart displays biochemical, thermogenic, and cardioprotective properties. However, the metabolic cross-talk between epicardial fat and the myocardium is largely unknown.

Ipilimumab and vemurafenib: two different routes for targeting melanoma.

Melanoma, a malignant tumor of melanocytes, causes the majority (75%) of all skin cancer-related deaths. The overall efficacy of different anti-cancer therapies on metastatic melanoma is quite limited, due to its high resistance to all forms of conventional treatments, including chemotherapy, radiotherapy and immunotherapy, leading to low patient survival rates. The present review identifies possible strategies for the treatment of advanced melanoma and describes two novel agents, Ipilimumab and Vemurafenib, which may now be useful for clinical practice.

Rapid human melanoma cell death induced by sanguinarine through oxidative stress.

Sanguinarine is a natural isoquinoline alkaloid derived from the root of Sanguinaria canadensis and from other poppy fumaria species, and is known to have a broad spectrum of pharmacological properties. Here we have found that sanguinarine, at low micromolar concentrations, showed a remarkably rapid killing activity against human melanoma cells. Time-lapse videomicroscopy showed rapid morphological changes compatible with an apoptotic cell death, which was further supported by biochemical markers, including caspase activation, poly(ADP-ribose) polymerase (PARP) cleavage and DNA breakdown.

Doxorubicin-induced cardiotoxicity: from bioenergetic failure and cell death to cardiomyopathy.

Doxorubicin (DOX) is an anticancer anthracycline that presents a dose-dependent and cumulative cardiotoxicity as one of the most serious side effects. Several hypotheses have been advanced to explain DOX cardiac side effects, which culminate in the development of life-threatening cardiomyopathy. One of the most studied mechanisms involves the activation of DOX molecule into a more reactive semiquinone by mitochondrial Complex I, resulting in increased oxidative stress.

Edelfosine and perifosine disrupt hepatic mitochondrial oxidative phosphorylation and induce the permeability transition.

Edelfosine and perifosine are alkylphospholipids that have been intensively studied as potential antitumor agents. Apoptotic cell death caused by these two compounds is mediated, at least in part, through mitochondria. Additionally, previous works demonstrated that edelfosine induces changes in mitochondrial membrane permeability that are somehow reduced by using cyclosporin A.

Involvement of mitochondrial and B-RAF/ERK signaling pathways in berberine-induced apoptosis in human melanoma cells.

The natural isoquinoline alkaloid berberine exhibits a wide spectrum of biological activities including antitumor activity, but its mechanism of action remains to be fully elucidated. Here, we report that berberine induced apoptosis in human melanoma cells, through a process that involved mitochondria and caspase activation. Berberine-induced activation of a number of caspases, including caspases 3, 4, 7, 8, and 9.

Berberine as a promising safe anti-cancer agent - is there a role for mitochondria?

Metabolic regulation is largely dependent on mitochondria, which play an important role in energy homeostasis. Imbalance between energy intake and expenditure leads to mitochondrial dysfunction, characterized by a reduced ratio of energy production (ATP production) to respiration. Due to the role of mitochondrial factors/events in several apoptotic pathways, the possibility of targeting that organelle in the tumor cell, leading to its elimination is very attractive, although the safety issue is problematic.

Mitochondrial toxicity of the phyotochemicals daphnetoxin and daphnoretin--relevance for possible anti-cancer application.

Daphnetoxin is a daphnane type orthoester diterpene found exclusively in plants of the family Thymelaeaceae while daphnoretin, a bis-coumarin derivative that is the major constituent of the bark of some plants of this family, can also be found in Leguminosae and Rutaceae. These two compounds are recognized to have different biological effects, including a possible anti-cancer activity. The subject of the present research was to compare their mitochondrial toxicity and also investigate a possible selectivity towards tumor cell lines.