Modulation of Tmem135 Leads to Retinal Pigmented Epithelium Pathologies in Mice.

Purpose: Aging is a critical risk factor for the development of retinal diseases, but how aging perturbs ocular homeostasis and contributes to disease is unknown. We identified transmembrane protein 135 (Tmem135) as a gene important for regulating retinal aging and mitochondrial dynamics in mice. Overexpression of Tmem135 causes mitochondrial fragmentation and pathologies in the hearts of mice.

Anorexia nervosa manifesting as massive ascites, hypercholesterolemia, and sequential binge eating in an 11-year-old girl: A case report.

Rationale: Anorexia nervosa (AN) is a serious eating disorder associated with a distorted body image. Hypercholesterolemia has been found in patients with AN but the mechanism of hyperlipidemia in AN remains little known. Ascites in patients with AN has been attributed to hypoalbuminemia and liver diseases, but massive ascites without the aforementioned etiologies has never been reported in AN.

Metabolic alterations caused by the mutation and overexpression of the gene.

Mitochondria are dynamic organelles undergoing fission and fusion. Proper regulation of this process is important for healthy aging process, as aberrant mitochondrial dynamics are associated with several age-related diseases/pathologies. However, it is not well understood how imbalanced mitochondrial dynamics may lead to those diseases and pathologies.

Loss of Chondroitin Sulfate Modification Causes Inflammation and Neurodegeneration in Mice.

One major aspect of the aging process is the onset of chronic, low-grade inflammation that is highly associated with age-related diseases. The molecular mechanisms that regulate these processes have not been fully elucidated. We have identified a spontaneous mutant mouse line, small with kinky tail (), that exhibits accelerated aging and age-related disease phenotypes including increased inflammation in the brain and retina, enhanced age-dependent retinal abnormalities including photoreceptor cell degeneration, neurodegeneration in the hippocampus, and reduced lifespan.

Reactive oxygen species-mediated switching expression of MMP-3 in stromal fibroblasts and cancer cells during prostate cancer progression.

Studies on the aberrant control of extracellular matrices (ECMs) have mainly focused on the role of malignant cells but less on that of stromal fibroblasts during cancer development. Herein, by using paired normal and prostate cancer-associated stromal fibroblasts (CAFs) derived from a coculture cell model and clinical patient samples, we demonstrated that although CAFs promoted prostate cancer growth, matrix metalloproteinase-3 (MMP-3) was lower in CAFs but elevated in prostate cancer cells relative to their normal counterparts. Furthermore, hydrogen peroxide was characterized as the central modulator for altered MMP-3 expression in prostate cancer cells and CAFs, but through different regulatory mechanisms.

Metabolomics Identifies Metabolic Markers of Maturation in Human Pluripotent Stem Cell-Derived Cardiomyocytes.

Cardiovascular disease is a leading cause of death worldwide. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) hold immense clinical potential and recent studies have enabled generation of virtually pure hPSC-CMs with high efficiency in chemically defined and xeno-free conditions. Despite these advances, hPSC-CMs exhibit an immature phenotype and are arrhythmogenic , necessitating development of strategies to mature these cells.

Cyproheptadine use in hepatocellular carcinoma.

This study was conducted to compare the effectiveness of Cyproheptadine (CY) use in patients with different stages of HCC who received different therapeutic modalities; such a comparison has not been conducted by previous large, prospective, randomized studies. We conducted a cohort study using the Taiwan Cancer Registry Database for analysis. We included patients diagnosed as having HCC from January 1, 2002, to December 31, 2011.

Mouse mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies.

While the aging process is central to the pathogenesis of age-dependent diseases, it is poorly understood at the molecular level. We identified a mouse mutant with accelerated aging in the retina as well as pathologies observed in age-dependent retinal diseases, suggesting that the responsible gene regulates retinal aging, and its impairment results in age-dependent disease. We determined that a mutation in the transmembrane 135 () is responsible for these phenotypes.

Combination treatment with ethyl pyruvate and IGF-I exerts neuroprotective effects against brain injury in a rat model of neonatal hypoxic-ischemic encephalopathy.

Neonatal hypoxic-ischemic (HI) brain injury causes severe brain damage in newborns. Following HI injury, rapidly accumulating oxidants injure neurons and interrupt ongoing developmental processes. The antioxidant, sodium pyruvate, has been shown to reduce neuronal injury in neonatal rats under conditions of oxygen glucose deprivation (OGD) and HI injury.

Genetic basis of age-dependent synaptic abnormalities in the retina.

Understanding the normal aging process will help us determine the mechanisms of how age-related diseases are caused and progress. A/J inbred mice have been shown to exhibit accelerated aging phenotypes in the retina including increased inflammation and photoreceptor cell degeneration, which resemble human aging symptoms. C57BL/6J (B6) inbred mice are less susceptible for these abnormalities, indicating the existence of genetic factor(s) that affect their severity.

Role of antioxidant enzymes in redox regulation of N-methyl-D-aspartate receptor function and memory in middle-aged rats.

Overexpression of superoxide dismutase 1 (SOD1) in the hippocampus results in age-dependent impaired cognition and altered synaptic plasticity suggesting a possible model for examining the role of oxidative stress in senescent neurophysiology. However, it is unclear if SOD1 overexpression involves an altered redox environment and a decrease in N-methyl-D-aspartate receptor (NMDAR) synaptic function reported for aging animals. Viral vectors were used to express SOD1 and green fluorescent protein (SOD1 + GFP), SOD1 and catalase (SOD1 + CAT), or GFP alone in the hippocampus of middle-aged (17 months) male Fischer 344 rats.

Serum protein oxidation by diesel exhaust particles: effects on oxidative stress and inflammatory response in vitro.

Considerable evidence shows a key role for protein modification in the adverse effects of chemicals; however, the interaction of diesel exhaust particles (DEP) with proteins and the resulting biological activity remains unclear. DEP and carbon black (CB) suspensions with and without bovine serum albumin (BSA) were used to elucidate the biological effects of air pollutants. The DEP and CB samples were then divided into suspensions and supernatants.

[Oxidative stress inhibits the protective effects of insulin-like growth factor-1 on cortical neurons of neonatal rat].

Objective: To explore the protective effects of insulin-like growth factor-1(IGF-1) on the survival and apoptosis of cortical neurons of neonatal rat under oxidative stress and its significance.

Method: Primary cortical neurons from newborn rat were cultured and the oxidative stress model was established. Then cells were randomly divided into IGF-1 group and control group.

Sodium pyruvate reduces hypoxic-ischemic injury to neonatal rat brain.

Background: Neonatal hypoxia-ischemia (HI) remains a major cause of severe brain damage and is often associated with high mortality and lifelong disability. Immature brains are extremely sensitive to HI, shown as prolonged mitochondrial neuronal death. Sodium pyruvate (SP), a substrate of the tricarboxylic acid cycle and an extracellular antioxidant, has been considered as a potential treatment for hypoxic-ischemic encephalopathy, but its effects have not been evaluated in appropriate animal models for hypoxic-ischemic encephalopathy.

Disruption of NMDAR-CRMP-2 signaling protects against focal cerebral ischemic damage in the rat middle cerebral artery occlusion model.

Collapsin response mediator protein 2 (CRMP-2), traditionally viewed as an axon/dendrite specification and axonal growth protein, has emerged as nidus in regulation of both pre- and post-synaptic Ca ( 2+) channels. Building on our discovery of the interaction and regulation of Ca ( 2+) channels by CRMP-2, we recently identified a short sequence in CRMP-2 which, when appended to the transduction domain of HIV TAT protein, suppressed acute, inflammatory and neuropathic pain in vivo by functionally uncoupling CRMP-2 from the Ca ( 2+) channel. Remarkably, we also found that this region attenuated Ca ( 2+) influx via N-methylD-Aspartate receptors (NMDARs) and reduced neuronal death in a moderate controlled cortical impact model of traumatic brain injury (TBI).

Influence of viral vector-mediated delivery of superoxide dismutase and catalase to the hippocampus on spatial learning and memory during aging.

Aims: Studies employing transgenic mice indicate that overexpression of superoxide dismutase 1 (SOD1) improves memory during aging. It is unclear whether the improvement is due to a lifetime of overexpression, decreasing the accumulation of oxidized molecules, or if increasing antioxidant enzymes in older animals could reduce oxidative damage and improve cognitive function. We used adeno-associated virus to deliver antioxidant enzymes (SOD1, SOD2, catalase [CAT], and SOD1+CAT) to the hippocampus of young (4 months) and aged (19 months) F344/BN F1 male rats and examined memory-related behavioral performance 1 month and 4 months postinjection.

Influence of late-life exposure to environmental enrichment or exercise on hippocampal function and CA1 senescent physiology.

Aged (20-22 months) male Fischer 344 rats were randomly assigned to sedentary (A-SED), environmentally-enriched (A-ENR), or exercise (A-EX) conditions. After 10-12 weeks of differential experience, the 3 groups of aged rats and young sedentary controls were tested for physical and cognitive function. Spatial discrimination learning and memory consolidation, tested on the water maze, were enhanced in environmentally-enriched compared with sedentary.

Delayed IGF-1 treatment reduced long-term hypoxia-ischemia-induced brain damage and improved behavior recovery of immature rats.

Cerebral hypoxia-ischemia during the perinatal period is the single most important cause of acute newborn mortality and chronic disability. Despite our increasing understanding of the mechanisms of neuronal injury, an effective clinical therapy has yet to be established to mitigate brain damage and improve the prognosis and well-being of these newborn patients. Insulin-like growth factor 1 (IGF-1) is a well-known neurotrophic factor, essential for the survival and functional maturation of immature neurons.

Molecular architecture of myelinated peripheral nerves is supported by calorie restriction with aging.

Peripheral nerves from aged animals exhibit features of degeneration, including marked fiber loss, morphological irregularities in myelinated axons and notable reduction in the expression of myelin proteins. To investigate how protein homeostatic mechanisms change with age within the peripheral nervous system, we isolated Schwann cells from the sciatic nerves of young and old rats. The responsiveness of cells from aged nerves to stress stimuli is weakened, which in part may account for the observed age-associated alterations in glial and axonal proteins in vivo.

IGF-I improved bone mineral density and body composition of weaver mutant mice.

Our recent report on a parallel decrease in the body weights and serum IGF-I levels of weaver mice suggests that IGF-I's endocrine function may be impaired in neurodegenerative diseases. To further understand the overall effects of IGF-I deficiency on the postnatal growth, we measured bone mineral density (BMD), bone mineral content (BMC), lean body mass (LBM) and fat mass in male and female weaver mice and wild-type littermates on D21 (prepuberty), D45 (puberty), and D60 (postpuberty) using dual-energy X-ray absorptiometry (DEXA). In both male and female weaver mice, we found that the levels of circulating IGF-I paralleled those of BMD, BMC, and LBM, but not the fat mass.

Role of the GH/IGF-I axis in the growth retardation of weaver mice.

IGF-I is a well-established anabolic growth factor essential for growth and development. Although the role of the GH/IGF-I axis is established for normal postnatal growth, its functional state in neurodegenerative diseases is not fully characterized. The weaver mutant mouse is a commonly used model for studying hereditary cerebellar ataxia and provides an opportunity to investigate the function of IGF-I in postnatal growth following neurodegeneration.

Temperature-dependent developmental plasticity of Drosophila neurons: cell-autonomous roles of membrane excitability, Ca2+ influx, and cAMP signaling.

Environmental temperature is an important factor exerting pervasive influence on neuronal morphology and synaptic physiology. In the Drosophila brain, axonal arborization of mushroom body Kenyon cells was enhanced when flies were raised at high temperature (30 degrees C rather than 22 degrees C) for several days. Isolated embryonic neurons in culture that lacked cell-cell contacts also displayed a robust temperature-induced neurite outgrowth.

Cesium chloride protects cerebellar granule neurons from apoptosis induced by low potassium.

Neuronal apoptosis plays a critical role in the pathogenesis of neurodegenerative disorders, and neuroprotective agents targeting apoptotic signaling could have therapeutic use. Here we report that cesium chloride, an alternative medicine in treating radiological poison and cancer, has neuroprotective actions. Serum and potassium deprivation induced cerebellar granule neurons to undergo apoptosis, which correlated with the activation of caspase-3.

Lithium: a novel treatment for Alzheimer's disease?

Lithium is an alkali metal. First described as a mood stabilizer in 1949, it remains an efficacious treatment for bipolar disorders. Recent emerging evidence of its neuroprotective and neurogenic effects alludes to lithium's potential therapeutic use in stroke and neurodegenerative diseases.