Functional Assessment and Patient-Related Outcomes after Gluteus Maximus Flap Transfer in Patients with Severe Hip Abductor Deficiency

(1) Background: Degeneration of the hip abductor mechanism, a well-known cause of functional limitation, is difficult to treat and is associated with a reduced health-related quality of life (HRQOL). The gluteus maximus muscle flap is a treatment option to support a severely degenerative modified gluteus medius muscle. Although several reports exist on the clinical outcome, there remains a gap in the literature regarding HRQOL in conjunction with functional results. (2) Methods: The present study consists of 18 patients with a mean age of 64 (53‒79) years, operatively treated with a gluteus maximus flap due to chronic gluteal deficiency. Fifteen (83%) of these patients presented a history of total hip arthroplasty or revision arthroplasty. Pre and postoperative pain, Trendelenburg sign, internal rotation lag sign, trochanteric pain syndrome, the Harris Hip Score (HHS), and abduction strength after Janda (0‒5) were evaluated. Postoperative patient satisfaction and health-related quality of life, according to the Short Form 36 (SF-36), were used as patient-reported outcome measurements (PROMs). Postoperative MRI scans were performed in 13 cases (72%). (3) Results: Local pain decreased from NRS 6.1 (0-10) to 4.9 (0-8) and 44% presented with a negative Trendelenburg sign postoperatively. The overall HHS results (p = 0.42) and muscular abduction strength (p = 0.32) increased without significance. The postoperative HRQOL reached 46.8 points (31.3-62.6) for the mental component score and 37.1 points (26.9-54.7) for the physical component score. The physical component results presented a high level of positive correlation with HHS scores postoperatively (R = 0.88, p < 0.001). Moreover, 72% reported that they would undergo the operative treatment again. The MRI overall showed no significant further loss of muscle volume and no further degeneration of muscular tissue. (4) Conclusions: Along with fair functional results, the patients treated with a gluteus maximus flap transfer presented satisfying long-term PROMs. Given this condition, the gluteus maximus muscle flap transfer is a viable option for selected patients with chronic gluteal deficiency

Characterizing Sterol Defect Suppressors Uncovers a Novel Transcriptional Signaling Pathway Regulating Zymosterol Biosynthesis

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Cell Stress – a new journal for cellular pathophysiology

Launched by over a hundred high-carat founding editors, including five Nobel Laureates and more than 30 members of the National Academy of Sciences, Cell Stress emerges as a new online-only journal that focuses on disease-relevant cellular responses to endogenous and exogenous stress. Cell Stress is a peer-reviewed publishing platform for high-impact research in all areas of pathophysiology with a rigorous open access policy that allows maximal visibility and transparency for the publication of excellent science. Cell Stress thus offers readers and experts all over the world a common, peer-reviewed platform to develop and transfer technical and experimental knowledge, to understand cellular and organismal stress and, ultimately, to combat disease

Perspective beyond Cancer Genomics: Bioenergetics of Cancer Stem Cells

Although the notion that cancer is a disease caused by genetic and epigenetic alterations is now widely accepted, perhaps more emphasis has been given to the fact that cancer is a genetic disease. It should be noted that in the post-genome sequencing project period of the 21st century, the underlined phenomenon nevertheless could not be discarded towards the complete control of cancer disaster as the whole strategy, and in depth investigation of the factors associated with tumorigenesis is required for achieving it. Otto Warburg has won a Nobel Prize in 1931 for the discovery of tumor bioenergetics, which is now commonly used as the basis of positron emission tomography (PET), a highly sensitive noninvasive technique used in cancer diagnosis. Furthermore, the importance of the cancer stem cell (CSC) hypothesis in therapy-related resistance and metastasis has been recognized during the past 2 decades. Accumulating evidence suggests that tumor bioenergetics plays a critical role in CSC regulation; this finding has opened up a new era of cancer medicine, which goes beyond cancer genomics

Dietary spermidine for lowering high blood pressure

Loss of cardiac macroautophagy/autophagy impairs heart function, and evidence accumulates that an increased autophagic flux may protect against cardiovascular disease. We therefore tested the protective capacity of the natural autophagy inducer spermidine in animal models of aging and hypertension, which both represent major risk factors for the development of cardiovascular disease. Dietary spermidine elicits cardioprotective effects in aged mice through enhancing cardiac autophagy and mitophagy. In salt-sensitive rats, spermidine supplementation also delays the development of hypertensive heart disease, coinciding with reduced arterial blood pressure. The high blood pressure-lowering effect likely results from improved global arginine bioavailability and protection from hypertension-associated renal damage. The polyamine spermidine is naturally present in human diets, though to a varying amount depending on food type and preparation. In humans, high dietary spermidine intake correlates with reduced blood pressure and decreased risk of cardiovascular disease and related death. Altogether, spermidine represents a cardio- and vascular- protective autophagy inducer that can be readily integrated in common diets

Nucleocytosolic depletion of the energy metabolite acetyl-coenzyme a stimulates autophagy and prolongs lifespan.

Healthy aging depends on removal of damaged cellular material that is in part mediated by autophagy. The nutritional status of cells affects both aging and autophagy through as-yet-elusive metabolic circuitries. Here, we show that nucleocytosolic acetyl-coenzyme A (AcCoA) production is a metabolic repressor of autophagy during aging in yeast. Blocking the mitochondrial route to AcCoA by deletion of the CoA-transferase ACH1 caused cytosolic accumulation of the AcCoA precursor acetate. This led to hyperactivation of nucleocytosolic AcCoA-synthetase Acs2p, triggering histone acetylation, repression of autophagy genes, and an age-dependent defect in autophagic flux, culminating in a reduced lifespan. Inhibition of nutrient signaling failed to restore, while simultaneous knockdown of ACS2 reinstated, autophagy and survival of ach1 mutant. Brain-specific knockdown of Drosophila AcCoA synthetase was sufficient to enhance autophagic protein clearance and prolong lifespan. Since AcCoA integrates various nutrition pathways, our findings may explain diet-dependent lifespan and autophagy regulation

Targeting GATA transcription factors – a novel strategy for anti-aging interventions?

GATA transcription factors (TFs) constitute a conserved family of zinc-finger TFs that fulfill diverse functions across eukaryotes. Accumulating evidence suggests that GATA TFs also play a role in lifespan regulation. In a recent study, we identified a natural polyphenol, 4,4’-dimethoxychalcone (DMC), that extends lifespan depending on reduced activity of distinct GATA TFs. Prolonged lifespan by DMC treatment depends on autophagy, a protective cellular self-cleansing mechanism. In yeast, DMC reduces the activity of the GATA TF Gln3 and, genetic deletion of Gln3 is sufficient to increase autophagy levels during cellular aging. In addition, we observed similar changes in the abundance of several amino acids in the metabolome of DMC-treated and GATA/Gln3 depleted cells. Here, we examine current data on the involvement of GATA TFs in the regulation of autophagy and longevity in different organisms and explore if GATA TFs might be suitable targets for anti-aging interventions

4,4’Dimethoxychalcone: a natural flavonoid that promotes health through autophagy-dependent and -independent effects

The age-induced deterioration of the organism results in detrimental and ultimately lethal pathologies. The process of aging itself involves a plethora of different mechanisms that should be subverted concurrently to delay and/or prevent age- related maladies. We have identified a natural compound, 4,4ʹ-dimethoxychalcone (DMC), which promotes longevity in yeast, worms and flies, and protects mice from heart injury and liver toxicity. Interestingly, both the DMC-mediated lifespan extension and the cardioprotection depend on macroautophagy/autophagy whereas hepatoprotection does not. DMC induces autophagy by inhibiting specific GATA transcription factors (TFs), independently of the TORC1 kinase pathway. The autophagy-independent beneficial effects of DMC might involve its antioxidative properties. DMC treatment results in a phylogenetically conserved, systemic impact on the metabolome, which is most prominently characterized by changes in cellular amino acid composition. Altogether, DMC exerts multiple, geroprotective effects by igniting distinct pathways, and thus represents a potential pharmacological agent that delays aging through multipronged effects

The Warburg Effect Suppresses Oxidative Stress Induced Apoptosis in a Yeast Model for Cancer

BACKGROUND: Otto Warburg observed that cancer cells are often characterized by intense glycolysis in the presence of oxygen and a concomitant decrease in mitochondrial respiration. Research has mainly focused on a possible connection between increased glycolysis and tumor development whereas decreased respiration has largely been left unattended. Therefore, a causal relation between decreased respiration and tumorigenesis has not been demonstrated. METHODOLOGY/PRINCIPAL FINDINGS: For this purpose, colonies of Saccharomyces cerevisiae, which is suitable for manipulation of mitochondrial respiration and shows mitochondria-mediated cell death, were used as a model. Repression of respiration as well as ROS-scavenging via glutathione inhibited apoptosis and conferred a survival advantage during seeding and early development of this fast proliferating solid cell population. In contrast, enhancement of respiration triggered cell death. CONCLUSION/SIGNIFICANCE: Thus, the Warburg effect might directly contribute to the initiation of cancer formation--not only by enhanced glycolysis--but also via decreased respiration in the presence of oxygen, which suppresses apoptosis

Targeting GATA transcription factors – a novel strategy for anti-aging interventions?

GATA transcription factors (TFs) constitute a conserved family of zinc-finger TFs that fulfill diverse functions across eukaryotes. Accumulating evidence suggests that GATA TFs also play a role in lifespan regulation. In a recent study, we identified a natural polyphenol, 4,4’-dimethoxychalcone (DMC), that extends lifespan depending on reduced activity of distinct GATA TFs. Prolonged lifespan by DMC treatment depends on autophagy, a protective cellular self-cleansing mechanism. In yeast, DMC reduces the activity of the GATA TF Gln3 and, genetic deletion of Gln3 is sufficient to increase autophagy levels during cellular aging. In addition, we observed similar changes in the abundance of several amino acids in the metabolome of DMC-treated and GATA/Gln3 depleted cells. Here, we examine current data on the involvement of GATA TFs in the regulation of autophagy and longevity in different organisms and explore if GATA TFs might be suitable targets for anti-aging interventions