The Endoplasmic Reticulum Stress Response in Neuroprogressive Diseases: Emerging Pathophysiological Role and Translational Implications

The endoplasmic reticulum (ER) is the main cellular organelle involved in protein synthesis, assembly and secretion. Accumulating evidence shows that across several neurodegenerative and neuroprogressive diseases, ER stress ensues, which is accompanied by over-activation of the unfolded protein response (UPR). Although the UPR could initially serve adaptive purposes in conditions associated with higher cellular demands and after exposure to a range of pathophysiological insults, over time the UPR may become detrimental, thus contributing to neuroprogression. Herein, we propose that immune-inflammatory, neuro-oxidative, neuro-nitrosative, as well as mitochondrial pathways may reciprocally interact with aberrations in UPR pathways. Furthermore, ER stress may contribute to a deregulation in calcium homoeostasis. The common denominator of these pathways is a decrease in neuronal resilience, synaptic dysfunction and even cell death. This review also discusses how mechanisms related to ER stress could be explored as a source for novel therapeutic targets for neurodegenerative and neuroprogressive diseases. The design of randomised controlled trials testing compounds that target aberrant UPR-related pathways within the emerging framework of precision psychiatry is warranted

State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS)

PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available) adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy

<em>Rheum spiciforme</em> Royle—the medicinal herb with positive modulatory effect on controlled <em>in vitro</em> oxidative stress

556-564Oxidative stress is the root cause of many diseases, affecting the humans by deranging the balance between the oxidants and antioxidants. Pathologies, such as Alzheimer’s, Parkinson’s, diabetes and cancer have been well associated with the production of free radicals during various metabolic processes. Many medicinal plants are used to treat such kind of diseases since ancient times. Here, we evaluated the medicinal herb Rheum spiciformis Royle (RS), used commonly in folklore to treat many aliments for its potential against oxidative stress. Five different extracts (aqueous, chloroform, ethyl acetate, methanol and PET ether) of RS were evaluated against oxidative stress generated in vitro. Phytochemical constituents were assessed followed by total phenolics, DPPH, reducing power, hydroxyl radical scavenging activity and in vitro calf thymus DNA damage. The highest phenolic content (TPC) of 1191.65 mg GAE/g was observed in RS-MeOH extract. DPPH radical scavenging activity was found to be highest in RS-MeOH (96.60%) with IC50 125.91 µg/mL. The reducing power of the extracts increased in a concentration dependent manner. Again superoxide radical scavenging activity of RS extracts with IC50 values 34.10 µg/mL (RS-MeOH) for methanol was highest. The H2O2 scavenging activity 84.76 µg/mL shown by RS-MeOH extract at 250 µg/mL of plant extracts was the maximum. RS-MeOH showed great effect to scavenge free radicals as such prevents Calf thymus DNA damage induced by Fenton reaction. These results clearly indicate that RS-MeOH and RS-EtA among the five extracts possesses the highest positive modulatory effect on free radical scavenging on wide variety of free radicals as such can be employed as potential antioxidant and anti-inflammatory agent against various oxidative stress related pathological conditions

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Not AvailableThe present investigation was conducted on thirty eight accessions of onion at the experimental farm of Central Institute of temperate Horticulture to study the variability and their interrelationship and divergence pattern based on quantitative and qualitative traits during 2009 to 2011. Multivariate analysis was used to classify 38 long day onion accessions. All accessions were grouped into six different clusters. The highest inter cluster distance was observed between IV and V and lowest between II and VI. Based on cluster means the important cluster was I for plant height and percent marketable bulbs cluster IV for mean yield, total yield and equatorial diameter and cluster III for the number of leaves, collar thickness and average bulb weight. Accordingly, parents could be selected for hybridization. Principal component analysis, first two principal component accessions accounted for 59.29% of the variance among 38Not Availabl