Frailty in elderly is very much familiar with a decline in the musculoskeletal system. Muscle degeneration in the lower organism was observed due to loss of anti-oxidant protein Sestrin. The aim of the study is to determine the level of Sestrin1 and Sestrin2 in the serum of frail and non-frail elderly to associate their impact in frailty syndrome. Subjects with age ≥ 65 years were enrolled from Geriatric Medicine OPD of All India Institute of Medical Sciences, New Delhi (N= 92). Among them, 51 subjects were identified as frail and rest 41 were regarded as non-frail according to “deficit accumulation model of Rockwood.” The study was performed by surface plasmon resonance and validated by western blot. Sestrin1 and Sestrin2 were found to be significantly reduced in frail compare to non-frail elderly. Furthermore, even after the adjustment for age, gender and education, the level of Sestrin1 and Sestrin2 remain significantly lower across the groups. The Sestrin1 level was significantly lower in various categories like age, gender, BMI, education, ADL, number of co-morbidity along with other clinico-pathological features. ROC analysis also revealed the distinction of frail and non-frail in respect to serum Sestrin1 and Sestrin2. This study highlighted the new and promising role of serum Sestrin in frail and non-frail elderly. In future, it can be utilized as molecular marker to assess the potential diagnostic value for clinical purpose.
It can be concluded that older patients with HNSCC and lung cancer have raised serums CDK4 levels, which has the potential to emerge as a biomarker in clinical practice.
Rho proteins operate as key regulators of the cytoskeleton, cell morphology and trafficking. Acting as molecular switches, the function of Rho GTPases is determined by guanosine triphosphate (GTP)/guanosine diphosphate (GDP) exchange and their lipidation via prenylation, allowing their binding to cellular membranes and the interaction with downstream effector proteins in close proximity to the membrane. A plethora of in vitro studies demonstrate the indispensable function of Rho proteins for cytoskeleton dynamics within different cell types. However, only in the last decades we have got access to genetically modified mouse models to decipher the intricate regulation between members of the Rho family within specific cell types in the complex in vivo situation. Translationally, alterations of the expression and/or function of Rho GTPases have been associated with several pathological conditions, such as inflammation and cancer. In the context of the GI tract, the continuous crosstalk between the host and the intestinal microbiota requires a tight regulation of the complex interaction between cellular components within the intestinal tissue. Recent studies demonstrate that Rho GTPases play important roles for the maintenance of tissue homeostasis in the gut. We will summarize the current knowledge on Rho protein function within individual cell types in the intestinal mucosa in vivo, with special focus on intestinal epithelial cells and T cells.
Alzheimer's disease (AD) is an accelerating neurodegenerative disorder. Dysfunction of mitochondria and oxidative stress contributes to the pathogenesis of AD. Sirtuins play a role in this pathway and can be a potential marker to study neurodegenerative changes. This study evaluated serum levels of all seven sirtuins (SIRT1 -SIRT7) proteins in three study groups: AD, Mild Cognitive Impairment (MCI), and Geriatric Control (GC) by Surface Plasmon Resonance (SPR) technique. Further, it was validated by the Western blot experiment. ROC analysis was performed to differentiate the study group based on the concentration of serum SIRT proteins. Out of seven sirtuins, serum SIRT1, SIRT3, and SIRT6 levels (mean ± SD) were signi cantly decreased in AD (1.65 ± 0.56, 3.15 ± 0.28, 3.36 ± 0.32ng/µl); compare to MCI (2.17 ± 0.39, 3.60 ± 0.51, 3.73 ± 0.48ng/µl) and GC (2.84 ± 0.47, 4.55 ± 0.48, 4.65 ± 0.55ng/µl). ROC analysis showed the cutoff value with high sensitivity and speci city for cognitive impairment (AD and MCI). The concentration declined signi cantly with the disease progression. No speci c difference was observed in case of other SIRTS between the study groups. This study reveals an inverse relation of serum SIRT1, SIRT3, and SIRT6 concentration with AD. ROC analysis showed that these serum proteins have greater accuracy in diagnosing of AD. This is the rst report of estimation of all seven serum sirtuins and the clinical relevance of SIRT3 and SIRT6 as serum protein markers for AD.
ObjectiveIncreased apoptotic shedding has been linked to intestinal barrier dysfunction and development of inflammatory bowel diseases (IBD). In contrast, physiological cell shedding allows the renewal of the epithelial monolayer without compromising the barrier function. Here, we investigated the role of live cell extrusion in epithelial barrier alterations in IBD.DesignTaking advantage of conditional GGTase and RAC1 knockout mice in intestinal epithelial cells (Pggt1biΔIEC and Rac1iΔIEC mice), intravital microscopy, immunostaining, mechanobiology, organoid techniques and RNA sequencing, we analysed cell shedding alterations within the intestinal epithelium. Moreover, we examined human gut tissue and intestinal organoids from patients with IBD for cell shedding alterations and RAC1 function.ResultsEpithelial Pggt1b deletion led to cytoskeleton rearrangement and tight junction redistribution, causing cell overcrowding due to arresting of cell shedding that finally resulted in epithelial leakage and spontaneous mucosal inflammation in the small and to a lesser extent in the large intestine. Both in vivo and in vitro studies (knockout mice, organoids) identified RAC1 as a GGTase target critically involved in prenylation-dependent cytoskeleton dynamics, cell mechanics and epithelial cell shedding. Moreover, inflamed areas of gut tissue from patients with IBD exhibited funnel-like structures, signs of arrested cell shedding and impaired RAC1 function. RAC1 inhibition in human intestinal organoids caused actin alterations compatible with arresting of cell shedding.ConclusionImpaired epithelial RAC1 function causes cell overcrowding and epithelial leakage thus inducing chronic intestinal inflammation. Epithelial RAC1 emerges as key regulator of cytoskeletal dynamics, cell mechanics and intestinal cell shedding. Modulation of RAC1 might be exploited for restoration of epithelial integrity in the gut of patients with IBD.
The resource allocation in Grid computing system needs to be scalable, reliable and smart. It should also be adaptable to change its allocation mechanism depending upon the environment and user's requirements. Therefore, a scalable and optimized approach for resource allocation where the system can adapt itself to the changing environment and the fluctuating resources is essentially needed. In this paper, a Teaching Learning based optimization approach for resource allocation in Computational Grids is proposed. The proposed algorithm is found to outperform the existing ones in terms of execution time and cost. The algorithm is simulated using GRIDSIM and the simulation results are presented.
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