Correction: Withaferin A (WFA) inhibits tumor growth and metastasis by targeting ovarian cancer stem cells.

[This corrects the article DOI: 10.18632/oncotarget.20170.

Withaferin A (WFA) inhibits tumor growth and metastasis by targeting ovarian cancer stem cells.

Ovarian cancer is the fifth leading cause of deaths due to cancer among women in the United States. In 2017, 22,440 women are expected to be diagnosed with ovarian cancer and 14,080 women will die with it. Currently used chemotherapies (Cisplatin or platinum/taxane combination) targets cancer cells, but spares cancer stem cells (CSCs), which are responsible for tumor relapse leading to recurrence of cancer.

Dementia-like pathology in type-2 diabetes: A novel microRNA mechanism.

Although type-2 diabetes (T2D) has been reported to increase the risk of cognitive dysfunction and dementia, the underlying mechanisms remain unclear. Dementia-like pathology is attributed to the accumulation of cellular prion protein (PrP) which plays a role in cognitive dysfunction. However, its involvement and regulation in diabetic dementia-like pathology is not well understood.

Curcumin-loaded embryonic stem cell exosomes restored neurovascular unit following ischemia-reperfusion injury.

We tested whether the combined nano-formulation, prepared with curcumin (anti-inflammatory and neuroprotective molecule) and embryonic stem cell exosomes (MESC-exo), restored neurovascular loss following an ischemia reperfusion (IR) injury in mice. IR-injury was created in 8-10 weeks old mice and divided into two groups. Out of two IR-injured groups, one group received intranasal administration of MESC-exo for 7days.

Microvascular dilation evoked by chemical stimulation of C-fibers in rats.

Activation of pulmonary C-fibers can reflexively decrease heart rate, blood pressure, and peripheral vascular resistance. However, the effects of these afferents on microvascular tone remain incompletely understood. In this study, we examined the effects of these afferents on microvascular tone in a striated muscle vascular bed.

Exercise and nutrition in myocardial matrix metabolism, remodeling, regeneration, epigenetics, microcirculation, and muscle.

Remodeling and myocardial matrix metabolism contributes to cardiac endothelium-myocyte (perivascular fibrosis), myocyte-myocyte (interstitial fibrosis), and mitochondrion-myocyte (fusion and fission) coupling. Matrix metalloproteinases (MMPs), and tissue inhibitor of metalloproteinases (TIMPs) play differential roles in different tissues and diseases. For example, although present in the heart, MMP-3 is known as stromelysin (i.

Exercise mitigates homocysteine - β2-adrenergic receptor interactions to ameliorate contractile dysfunction in diabetes.

We tested the hypothesis that exercise ameliorates contractile dysfunction by interfering with homocysteine - β2-adrenergic receptor (AR) interactions, inducing β2-adrenergic response and Gs (stimulatory G adenylyl cyclase dependent protein kinase), and lowering homocysteine level in diabetes. The effect of homocysteine on β2-AR was determined by (a) scoring the β2-AR in the cardiomyocytes treated with high dose of homocysteine using flow cytometry, and (b) co-localizing homocysteine with Gs (an inducer of β2-AR) in the cardiomyocytes obtained from C57BL/ 6J (WT) and db/ db mice using confocal microscopy. The effect of exercise on the protein-protein interactions of homocysteine and β2-AR in diabetes was evaluated by co-immunoprecipitation in the four groups of db/db mice: (1) sedentary, (2) treated with salbutamol (a β2-AR agonist), (3) swimming exercise, and (4) swimming + salbutamol treatment.

Synergism in hyperhomocysteinemia and diabetes: role of PPAR gamma and tempol.

Background: Hyperhomocysteinemia (HHcy) and hyperglycemia cause diabetic cardiomyopathy by inducing oxidative stress and attenuating peroxisome proliferator- activated receptor (PPAR) gamma. However, their synergistic contribution is not clear.

Methods: Diabetic Akita (Ins2+/-) and hyperhomocysteinemic cystathionine beta synthase mutant (CBS+/-) were used for M-mode echocardiography at the age of four and twenty four weeks.

Functional consequences of the collagen/elastin switch in vascular remodeling in hyperhomocysteinemic wild-type, eNOS-/-, and iNOS-/- mice.

A decrease in vascular elasticity and an increase in pulse wave velocity in hyperhomocysteinemic (HHcy) cystathionine-beta-synthase heterozygote knockout (CBS(-/+)) mice has been observed. Nitric oxide (NO) is a potential regulator of matrix metalloproteinase (MMP) activity in MMP-NO-tissue inhibitor of metalloproteinase (TIMP) inhibitory tertiary complex. However, the contribution of the nitric oxide synthase (NOS) isoforms eNOS and iNOS in the activation of latent MMP is unclear.

Stem cells as a therapeutic target for diabetes.

The rapidly increasing number of diabetes patients across the world poses a great challenge to the current therapeutic approach. The traditional method of exogenous supply of insulin has ephemeral effect and often causes lethal hypoglycemia that demands to develop a novel strategy. Recent investigations on regeneration of insulin producing cells (IPCs) revealed that in addition to primary source i.

Hypothermia and surgery: immunologic mechanisms for current practice.

Objective: To examine cellular and immunologic mechanisms by which intraoperative hypothermia affects surgical patients.

Summary Background Data: Avoidance of perioperative hypothermia has recently become a focus of attention as an important quality performance measure, aimed at optimizing the care of surgical patients. Anesthetized surgical patients are particularly at risk for hypothermia, which has been directly linked to the development of sequelae, such as coagulopathy, infection, morbid myocardial events, and death after surgery.

Congenic expression of tissue inhibitor of metalloproteinase in Dahl-salt sensitive hypertensive rats is associated with reduced LV hypertrophy.

Although congenic translocation of a segment from chromosome 10 from Lewis rat, containing an extracellular proteinase inhibitor gene, decreased blood pressure in Dahl-salt sensitive (DSS) rats, the relationship between the levels of matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinase (TIMP), and cardiac function was unclear. In this study we investigated the cardiac effects of congenic translocation of a segment from chromosome 10 from Lewis rat, containing an extracellular proteinase inhibitor gene, in Dahl-salt sensitive rats. To test the hypothesis that left ventricular (LV) hypertrophy in DSS rats was due to high MMP and low TIMP levels and the decrease in blood pressure in congenic rats was associated with increase in proteinase inhibitor expression, cardiac function and levels of MMP and TIMP were determined in 16 weeks male DSS (D), Lewis (L) and congenic (CL-10) rats.

Renal mitochondrial damage and protein modification in type-2 diabetes.

Although mitochondrial reduction-oxidation (redox) stress and increase in membrane permeability play an important role in diabetic-associated renal microvasculopathies, it is unclear whether the intra-renal mitochondrial oxidative stress induces mitochondrial protein modifications, leading to increase mitochondrial membrane permeability. The hypothesis is that mitochondrial oxidative stress induces mitochondrial protein modification and leakage in the mitochondrial membrane in type-2 diabetes. The present study was conducted to determine the involvement of intra-renal mitochondrial oxidative stress in mitochondrial protein modifications and modulation of membrane permeability in the setting of type-2 diabetes.

Cardiac synchronous and dys-synchronous remodeling in diabetes mellitus.

Glucose-mediated impairment of homocysteine (Hcy) metabolism and decrease in renal clearance contribute to hyperhomocysteinemia (HHcy) in diabetes. The Hcy induces oxidative stress, inversely relates to the expression of peroxisome proliferators activated receptor (PPAR), and contributes to diabetic complications. Extracellular matrix (ECM) functionally links the endothelium to the myocyte and is important for cardiac synchronization.

Adaptive-outward and maladaptive-inward arterial remodeling measured by intravascular ultrasound in hyperhomocysteinemia and diabetes.

Background: Coronary artery remodeling implies structural changes in the vessel wall in response to various pathophysiologic conditions. However, the classification of remodeling is unclear. We hypothesized that the adaptive, positive-outward remodeling is a reactive and compensatory response to the stress.

Pioglitazone mitigates renal glomerular vascular changes in high-fat, high-calorie-induced type 2 diabetes mellitus.

Our hypothesis is that impairment of peroxisome proliferator-activated receptor-gamma (PPARgamma) initiates renal dysfunction by increasing renal glomerular matrix metalloproteinase-2 (MMP-2) activity because of increased renal homocysteine (Hcy) and decreased nitric oxide (NO) levels. C57BL/6J mice were made diabetic (D) by being fed a high-fat-calorie diet, and an increase in PPARgamma activity was induced by adding pioglitazone (Pi) to the diet. Mice were grouped as follows: normal calorie diet (N), D, N+Pi, and D+Pi (n = 6/group).

Pioglitazone prevents cardiac remodeling in high-fat, high-calorie-induced Type 2 diabetes mellitus.

The agonists of peroxisome proliferator-activated receptor-gamma (PPARgamma) ameliorate cardiovascular complications associated with diabetes mellitus. We tested the hypothesis that recovery from ailing to failing myocardium in diabetes by PPARgamma agonist is in part due to decreased matrix metalloproteinase-9 (MMP-9) activation and left ventricular (LV) tissue levels of homocysteine (Hcy). C57BL/6J mice were made diabetic (D) by feeding them a high-fat calorie diet.

Mechanisms of endothelial dysfunction with development of type 1 diabetes mellitus: role of insulin and C-peptide.

Complications associated with insulin-dependent diabetes mellitus (type-1diabetes) primarily represent vascular dysfunction that has its origin in the endothelium. While many of the vascular changes are more accountable in the late stages of type-1diabetes, changes that occur in the early or initial functional stages of this disease may precipitate these later complications. The early stages of type-1diabetes are characterized by a diminished production of both insulin and C-peptide with a significant hyperglycemia.

Reduced alpha adrenergic mediated contraction of renal preglomerular blood vessels as a function of gender and aging.

As human males age, a decline in baroreflex-mediated elevation of blood pressure occurs due, at least in part, to a reduction in alpha-1 adrenergic vasoconstrictor function. Alpha adrenergic constriction is mediated by guanosine triphosphate binding Protein (G Protein) coupled signaling pathways. Alpha-1 A/C, B, and D adrenergic receptor expressions, measured by GeneChip array, are not reduced during aging in renal blood vessels of male or female rats.

Mitochondrial mechanism of oxidative stress and systemic hypertension in hyperhomocysteinemia.

Formation of homocysteine (Hcy) is the constitutive process of gene methylation. Hcy is primarily synthesized by de-methylation of methionine, in which s-adenosyl-methionine (SAM) is converted to s-adenosyl-homocysteine (SAH) by methyltransferase (MT). SAH is then hydrolyzed to Hcy and adenosine by SAH-hydrolase (SAHH).

The murine cardiac 26S proteasome: an organelle awaiting exploration.

Multiprotein complexes have been increasingly recognized as essential functional units for a variety of cellular processes, including the protein degradation system. Selective degradation of proteins in eukaryotes is primarily conducted by the ubiquitin proteasome system. The current knowledge base, pertaining to the proteasome complexes in mammalian cells, relies largely upon information gained in the yeast system, where the 26S proteasome is hypothesized to contain a 20S multiprotein core complex and one or two 19S regulatory complexes.

Decreased alpha-adrenergic constriction of renal preglomerular arteries occurs with age and is gender-specific in the rat.

Age and/or gender appear to moderate alpha-adrenergic mediated constrictor mechanisms found in the interlobar arteries of the Munich Wistar rat. We have determined the extent of constriction to alpha-adrenergic receptor stimulation using norepinephrine, phenylephrine and A61603 (α1A-adrenergic receptor agonist) as a function of age and gender. Norepinephrine produced less constriction in male-derived arteries at ages greater than eight months as compared to the younger adult male (four to six months).

Alpha 1 adrenergic receptor control of renal blood vessels during aging.

Aging humans and rats have a reduced renal vascular constriction response to stress, change in posture, or exercise. In this study, renal interlobar arteries from 9- (intermediate age) to 15-month-old (aging) male Wistar rats constricted less to alpha-adrenergic agonists than those of 4-month-old (young adult) rats. The reduced contraction to A61603 (alpha 1 A agonist) was similar to that to norepinephrine and phenylephrine.

Cyclo-oxygenase-2, endothelium and aortic reactivity during deoxycorticosterone acetate salt-induced hypertension.

Objective: To test the hypothesis that the enhanced vascular responsiveness to norepinephrine that occurs during deoxycorticosterone acetate (DOCA)-salt induced hypertension is causally related to increased expression of cyclo-oxygenase (COX)-2 and oxidative stress, which diminishes the vasomodulatory influence of endothelium-derived nitric oxide.

Methods: Four groups of age-matched, male Sprague-Dawley rats were studied: Sham (normotensive); DOCA-salt (hypertensive); DOCA-salt treated with manganese(III) tetra(4-benzoic acid) porphyrin chloride [MnTBAP, an antioxidant; 15 mg/kg intraperitoneally (i.p.

Hyperhomocysteinemic diabetic cardiomyopathy: oxidative stress, remodeling, and endothelial-myocyte uncoupling.

Accumulation of oxidized-matrix (fibrosis) between the endothelium (the endothelial cells embedded among the myocytes) and cardiomyocytes is a hallmark of diabetes mellitus and causes diastolic impairment. In diabetes mellitus, elevated levels of homocysteine activate matrix metalloproteinase and disconnect the endothelium from myocytes. Extracellular matrix functionally links the endothelium to the cardiomyocyte and is important for their synchronization.