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Analyzing fluid–structure interactions (FSI) is crucial in many engineering applications from modeling of blood flow to design of aircrafts. FSI problems are normally simulated using grid based methods, which is complicated and challenging due to the difficulties in modeling large deformations. In this work, we present a numerical model developed for solving FSI problems using smoothed particle hydrodynamics (SPH), which is a meshless particle based Lagrangian method widely used for solving fluid mechanics and heat transfer problems. Being meshless method, the discretization of complex domains and treatment of large deformations becomes easier in SPH. It has an attractive feature that the interpolating nodes also function as material component by carrying properties of the material and move according to the internal and external interactions. SPH uses a smoothing kernel function to approximate the field variables and its derivatives at a node from its neighboring nodes. With this perspective, we developed a numerical model to simulate the flow through a square lattice of stationary cylinders. The developed model captured the fluid dynamics and the velocity contour and the streamlines plot obtained are in good agreement with available results in the literature. We believe that this model can be extended to investigate complex fluid–structure interaction problems involving moving and deformable structures.

Cognitive impairment and dementia are the most frequently occurring nonmotor symptoms in Parkinson’s disease (PD), yet these symptoms are mostly overlooked and are not diagnosed and treated exceptionally like the cardinal motor symptoms in clinical practice. It is only in the late twentieth century that dementia has been recognized as a major clinical manifestation in PD. The possible mechanisms that cause dementia are complex with different patterns of cognitive behavior that disrupt the patient’s quality of life. It is preeminently considered that the cholinergic denervation in the basal forebrain region mediates dementia in PD. So far, dopamine-based therapy is the key objective in the treatment of PD and the nonmotor symptoms are mostly neglected. Interestingly, the loss of Tyrosine kinase receptor-A (TrkA) signaling in basal forebrain results in neuronal atrophy, which precedes cholinergic denervation and cognitive impairment. Nerve Growth Factor (NGF) binds to TrkA receptors, inducing a cascade of events like PI-3Kinase/Akt and MAPK signaling pathways that render cholinergic degeneration and upregulate the choline acetyltransferase activity and neuronal differentiation. Hence, TrkA receptor activation by small molecules might attenuate the dementia symptoms associated with PD, and may be targeted as a novel treatment strategy along with regular clinical agents.

Excessive cerebral deposition of amyloid-beta (Aβ) peptides with 40-42 amino acids are the major neuropathologic feature of Alzheimer's Disease (AD), accompanied by a progressive and functional decline in cognition. With the failing attempts in the development of new pharmacological intervention and due to suboptimal results from the existing therapies available for the treatment of AD, there is a constant hunt for a new therapeutic alternative to address this severe neurodegenerative disease. The present study aimed to investigate the neuroprotective effect of Hemidesmus indicus extract in Aβ (1-42) infused model of AD. Sporadic model of AD was achieved by intracerebroventricular (i.c.v) injection of Aβ (1-42) peptide in Wistar rats, followed by treatment with methanolic extract of H. indicus (MEHI) at 100 and 200 mg/kg for 28 days. Locomotor activity, Radial arm Maze task and Passive avoidance test were used for the assessment of neurobehavioral deficits. After completion of 28 days treatment protocol, animals were euthanized and brains were collected for neurochemical analysis. Reversal of cognitive impairment was observed by MEHI on Aβ (1-42) rats, as evidenced by improved spatial memory learning. Furthermore, MEHI attenuated Aβ (1-42) induced oxidative stress and inhibited acetylcholine esterase (AChE) activity. Collectively, these findings exhibited neuroprotective activity of MEHI by ameliorating Aβ (1-42) mediated neuronal damage, thereby can stand as a potential disease-modifying therapeutic for curbing AD pathology.

The complexity of the underlying pathogenesis of Alzheimer’s disease (AD) and substandard results of existing treatment, demands persistent research for the development of new therapeutics. As natural antioxidant has attracted considerable attention on this regards, the present study evaluated and validated antioxidant and anti-cholinesterase activity of Vernonia anthelmintica seeds. Different extracts were collected after sequential extraction of plant seeds by using pet ether, chloroform, ethyl acetate, methanol and water as solvents. Antioxidant activity of the extracts was tested by using superoxide, nitric oxide (NO) and 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assays, whereas, acetylcholine esterase (AChE) inhibition property was assessed by Ellman’s method. Results revealed that all the extracts produced some degree of both the activities in a concentration-dependent manner. While pet ether extract exhibited weakest, methanolic extract displayed potent radical scavenging and anti-cholinesterase properties in all the assays with IC50 of 159.71 μg/ml against AChE inhibition and 98.51, 120.22 and 170.79 μg/ml against superoxide, NO and DPPH radical scavenging assays respectively. Presence of an array of secondary metabolites with modest flavonoid and phenol content in the methanolic extract is accountable for these desired activities. Collectively, reports from our experiments covey that V. anthelmintica possess significant AChE inhibitory and antioxidant property and thus can be further evaluated in search of potential disease-modifying therapeutic for management of neurodegenerative diseases like AD.

Background: : Current drugs used for the treatment of hormone-dependent breast cancer function as anti-estrogens in the breast, in addition to Estrogen Receptor (ER) agonists in the uterus, thus elevate a woman’s risk of developing uterine cancer. This is due to the lack of selective binding and partial agonistic effect of these drugs towards estrogen receptors. In recent years, therefore, researchers have turned their attention towards antiestrogens devoid of these agonist properties and thus have a mechanism of action different from the existing drugs. Objective:: In this context, we report here the design, development and in vitro evaluation of some novel pharmacophores containing coumarin and fatty acid scaffolds for their anti-breast cancer activity. Methods: : A library of coumarin-fatty acid conjugates was designed using structure-based drug design approach. The conjugates which have shown good in silico results were then synthesized, characterized and evaluated for their anti-breast cancer activity by MTT assay, Apoptotic assay, Cell proliferation assay, Estrogen binding assay and Gene expression study. Results: Out of the fifteen compounds screened, two compounds, SAC-2 and LNAC-2, showed good activity with IC50 values 22µg/ml, 25μg/ml, respectively. These compounds suppressed the proliferation of ER overexpressed MCF-7 cells, increased ERα degradation and hence inactivate the ERα pathway. ER binding assay and gene expression RT-PCR study reveal that SAC-2 downregulated the expression of ERα receptor and AKT-1 gene. Conclusion:: Compound SAC-2 is a good antagonist to ER and hence has a potential for treating breast cancer and other cancers where AKT plays an important role.

Gamma-amino butyric acid (GABA) is a major inhibitory neurotransmitter found in several regions of the brain and known to have various significant physiological roles as a potent bioactive compound. Malfunction of GABAergic neuronal signaling prompts to cause severe psychiatric symptoms in numerous mental disorders. Several drugs are available in clinical practice for neuropsychiatric disorders targeting through GABAergic pathway, with notable adverse effects. Interestingly, in recent years, researchers are focusing on natural compounds altering GABAergic neurotransmission for various psychiatric disorders due to its wide range of therapeutic efficacy and safety. The enormous variety of natural compounds, namely alkaloids, flavonoids, terpenoids, polyacetylenic alcohols, alkanes and fatty acids were reported to alter the GABAergic transmission through its receptors and or by influencing the transmission, synthesis and metabolism of GABA. Natural compounds are able to cross the blood brain barrier and influence the GABA functions in order to treat anxiety, mania, schizophrenia and cognitive disorders. Therefore, this current chapter describes on natural products which have the potential to alter the GABAergic neurotransmission and its therapeutical benefits in treating several neuropsychiatry disorders using various pharmacological methods.

Advancements in brain imaging techniques have emerged as a significant tool in detecting Alzheimer's disease (AD) progression. The complicated cascade of AD progression can be detected using radio imaging, especially with Positron emission tomography (PET). The review focus on recently introduced investigational PET tracers targeting neurofibrillary tau aggregates found typically in AD. Herein, we also address the use of different PET tracers and the clinical implementation of established and newer generation tracers. This review also intends to discuss the importance of several PET radiotracers and challenges in PET imaging.

Purpose The purpose of this work is to investigate the optimization of automotive wheel rim using ansys. Design Methodology Approach In this study heavy stresses in the rim was developed, the critical stress and number cycles to failure were to be found. The purpose of the car wheel rim was to provide a firm base to hold the tire .Its dimensions and shape should be suitable to accommodate the particular tire required for the vehicle .In this study ,a car wheel rim considered .The wheel rim was designed by using modeling software SOLID WORKS V13.The solid model was then imported to ANSYS for static analysis. Findings The experimental results indicate that the static analysis is carried out by considering the three different materials namely steel alloy, alluminium alloy and their relative performance have been observed .In addition to this the rim is subjected to fatigue analysis using MSV fatigue software and its performance is observed .The results of static and fatigue analysis obtained from three different materials reveals that the steel alloy is the best material of wheel rim. Originality value This paper explains the effect of different materials on the wheel through by vonmises stresses and number of cycles in fatigue analysis. R. Ashok Kumar | G. Amarnath | K. Padmanaban | S. Karuppusamy | I. Justin Antony Raj "Experimental Studies of Optimization of Automotive wheel Rim using ANSYS" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-3 , April 2019, URL: https://www.ijtsrd.com/papers/ijtsrd22778.pdf

Diosgenin is a neurosteroid derived from the plants and has been previously reported for its numerous health beneficial properties, such as anti-arrhythmic, hypolipidemic, and antiproliferative effects. Although several studies conducted earlier suggested cognition enhancement actions of diosgenin against neurodegenerative disorders, but the molecular mechanisms underlying are not clearly understood. In the present study, we investigated the neuroprotective effect of diosgenin in the wistar rats that received an intracerebroventricular injection of Amyloid-β (1–42) peptides, representing a rodent model of Alzheimer’s disease (AD). Animals were treated with 100 and 200 mg/kg/p.o of diosgenin for 28 days, followed by Amyloid-β (1–42) peptides infusion. Animals were assessed for the spatial learning and memory by using radial arm maze and passive avoidance task. Subsequently, animals were euthanized and brains were collected for biochemical estimations and histopathological studies. Our results revealed that, diosgenin administration dose dependently improved the spatial learning and memory and protected the animals from Amyloid-β (1–42) peptides induced disrupted cognitive functions. Further, biochemical analysis showed that diosgenin successfully attenuated Amyloid-β (1–42) mediated plaque load, oxidative stress, neuroinflammation and elevated acetylcholinesterase activity. In addition, histopathological evaluation also supported neuroprotective effects of diosgenin in hippocampus of rat brain when assessed using hematoxylin-eosin and Cresyl Violet staining. Thus, the aforementioned effects suggested protective action of diosgenin against Aβ (1–42) induced neuronal damage and thereby can serve as a potential therapeutic candidate for AD.

Cognitive impairment and dementia are the most frequently occurring nonmotor symptoms in Parkinson’s disease (PD), yet these symptoms are mostly overlooked and are not diagnosed and treated exceptionally like the cardinal motor symptoms in clinical practice. It is only in the late twentieth century that dementia has been recognized as a major clinical manifestation in PD. The possible mechanisms that cause dementia are complex with different patterns of cognitive behavior that disrupt the patient’s quality of life. It is preeminently considered that the cholinergic denervation in the basal forebrain region mediates dementia in PD. So far, dopamine-based therapy is the key objective in the treatment of PD and the nonmotor symptoms are mostly neglected. Interestingly, the loss of Tyrosine kinase receptor-A (TrkA) signaling in basal forebrain results in neuronal atrophy, which precedes cholinergic denervation and cognitive impairment. Nerve Growth Factor (NGF) binds to TrkA receptors, inducing a cascade of events like PI-3Kinase/Akt and MAPK signaling pathways that render cholinergic degeneration and upregulate the choline acetyltransferase activity and neuronal differentiation. Hence, TrkA receptor activation by small molecules might attenuate the dementia symptoms associated with PD, and may be targeted as a novel treatment strategy along with regular clinical agents.

Background: There is a constant hunt for the development of new therapeutic alternative to address Alzheimer's disease (AD) due to its failing attempts in the evolution of new therapies and suboptimal results from the existing pharmacological interventions for the treatment of this severe neurodegenerative disease. Vernonia anthelmintica is an extensively used medicinal plant in Indian traditional medicine with wide range of therapeutic values. However, there is insufficient scientific documentation available for its protective effect against cognitive disorders. Objectives: The objective of the current investigation is to explore the neuroprotective activity of methanolic extract of V. anthelmintica (MEVA) in amyloid-beta (Aβ) (1–42) infused sporadic model of AD. Materials and Methods: Adult healthy male Wistar rats were treated orally with 250 mg/kg and 500 mg/kg of MEVA for 28 days, after a week from intracerebroventricular (i.c.v) infusion of Aβ (1–42) peptides followed by assessment of neurobehavioral deficits. Subsequently, animals were euthanized and brains were collected for estimation and quantification of neurochemical biomarkers including antioxidant enzymes, neurotransmitters, plaque load, and inflammatory mediators. Results: Dose-dependent reversal of cognitive impairment was observed upon MEVA treatment in amyloid intoxicated rats as corroborated by improved learning and memory and diminished oxidative stress, cholinergic hypofunction, and neuroinflammation induced by Aβ (1–42). Conclusion: Collectively, evidence-based data suggested the promising neurotherapeutic potential of V. anthelmintica and thereby can stand as a novel entity for curbing AD pathology.

Neurological disorders such as Alzheimer’s Disease (AD), Parkinsons’s Disease (PD) and Cerebral Ischemic Stroke (CIS) are responsible for morbidities in almost a billion people and it is rising with increase in older population. AD is responsible for most dementia cases reported worldwide and is marked by the loss of memory and aggregation of Amyloid beta peptide (AsP) and Neurofibrillary tangle (NFT). Oxidative stress, apoptosis are few of the factors that influence the pathophysiology. PD is characterized by genetic abnormalities, mitochondrial dysfunction, oxidative stress, excitotoxicity, calcium and iron overload and neuroinflammation and manifests as rigidity and bradykinesia. CIS is caused by reduced cerebral blood flow and impaired metabolic processes. The generation of free radicals and elevation of Ca2+ levels along with inflammatory cytokines, carries out the process. The use of plants for various disease condition is as old as history. The recent advancements in scientific drug development has hastened the discovery process and has opened doors to new discoveries having potential in treatment of neurological disorders such as AD, PD and CIS. These investigations has resulted in discovery of plants and plant extracts with potential neuroprotective effects. However, these discoveries require further validation and scientific proofs to be applied in clinical scenario. Interestingly, these plant based treatments can be co-administered with existing drugs or can be even used as monotherapy, depending on the advancements in this field.

Cases of Diabetes mellitus around the world are increasing day by day. It has been predicted that India, China and United States will be having the largest number of diabetic patients by 2030. Therefore, the anti-diabetic study is attracted a huge number of scientists and various in-vitro and in-vivo models has been developed for anti-diabetic study. In drug development, the in-vitro techniques are an important method of confirming a particular biological activity of a compound before animal experiments. In vitro cell lines are alternative to animal models to study the particular activity of drugs. To produce more reproducible results, the in-vitro cell lines from clonal cells, cell lines are used. Characteristics of cell lines are constantly changing because of continuous growth of cells without any limits being its disadvantage. This review attempts to bring together all reported in-vitro cell line models to study the anti-diabetic activity. These cell lines may prove essential for the development of new drugs for the treatment of diabetes mellitus. Study of anti-diabetics activity of various agents in cell line models is important for improving the knowledge and in providing a clear understanding of pathogenesis leading to the discovery of new therapies for the disease. Many cell lines have been discovered in past few decades for the in-vitro studies involving diabetes mellitus. The generation of cell lines may bedecreased the number of animals used for in-vivo studies. Using cell lines for anti-diabetic studies also put aside the painful techniques in the in-vivo studies.

Folate conjugated Simvastatin loaded Solid lipid nanoparticles (SIM-SLNs) were constructed after the preformulation studies such as Differential calorie metry (DSC), Fourier transform infrared spectroscopy (FTIR) and partition coefficient studies. SIM-SLNs were evaluated in terms of particles size, zeta potential, drug encapsulation, and drug release. The cytotoxicity of the SLNs was evaluated on MCF-7 Human Breast Carcinoma cells (MCF-7 cells) by MTT assay. In vivo pharmacokinetic parameters and Bio-distribution were observed in Wistar rats. The particle size of SIM-SLNs (F6) was 177.4 nm with a zeta potential of -5.16 mV. The entrapment efficiency and drug loading was found to be higher in SIM-SLNs. SLN formulation released the drug in sustained manner over a period of 24 hours. Various kinetic models were fitted and it was observed that Higuchi’s model was the best fit model. SIM-SLNs showed highest cytotoxicity in tumor cells in vitro. In vivo studies showed that there is significant increase in the pharmacokinetic parameters and Bio-distribution of SIM-SLNs when compared to the pure drug suspension. Higher relative bioavailability would be due to avoidance of first-pass hepatic metabolism by intestinal lymphatic transport, which circumvents the liver. According to these results, the novel SIM-SLNs provided sustained release of the drug, and these systems are the preferred drug carriers for lipophilic drugs to overcome the oral bioavailability problem of drug and to increase targeting efficacy to the specific organs as breast, prostate and ovary.