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Calcium homeostasis modulator 1 (CALHM1) is a protein responsible for causing Alzheimer’s disease. In the absence of an experimentally designed protein molecule, homology modelling was performed. Through homology modelling, different CALHM1 models were generated and validated through Rampage. To carry out further in silico studies, through molecular docking and molecular dynamics simulation experiments, various flavonoids and alkaloids from Bauhinia variegata were utilised as inhibitors to target the protein (CALHM1). The sequence of CALHM1 was retrieved from UniProt and the secondary structure prediction of CALHM1 was done through CFSSP, GOR4, and SOPMA methods. The structure was identified through LOMETS, MUSTER, and MODELLER and finally, the structures were validated through Rampage. Bauhinia variegata plant was used to check the interaction of alkaloids and flavonoids against CALHM1. The protein and protein–ligand complex were also validated through molecular dynamics simulations studies. The model generated through MODELLER software with 6VAM A was used because this model predicted the best results in the Ramachandran plot. Further molecular docking was performed, quercetin was found to be the most appropriate candidate for the protein molecule with the minimum binding energy of −12.45 kcal/mol and their ADME properties were analysed through Molsoft and Molinspiration. Molecular dynamics simulations showed that CALHM1 and CALHM1–quercetin complex became stable at 2500 ps. It may be seen through the study that quercetin may act as a good inhibitor for treatment. With the help of an in silico study, it was easier to analyse the 3D structure of the protein, which may be scrutinized for the best-predicted model. Quercetin may work as a good inhibitor for treating Alzheimer’s disease, according to in silico research using molecular docking and molecular dynamics simulations, and future in vitro and in vivo analysis may confirm its effectiveness.

A special class of proteins called Toll-like receptors (TLRs) are an essential part of the innate immune system, connecting it to the adaptive immune system. There are 10 different Toll-Like Receptors that have been identified in human beings. TLRs are part of the central nervous system (CNS), showing that the CNS is capable of the immune response, breaking the long-held belief of the brain’s “immune privilege” owing to the blood–brain barrier (BBB). These Toll-Like Receptors are present not just on the resident macrophages of the central nervous system but are also expressed by the neurons to allow them for the production of proinflammatory agents such as interferons, cytokines, and chemokines; the activation and recruitment of glial cells; and their participation in neuronal cell death by apoptosis. This study is focused on the potential roles of various TLRs in various neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s disease (AD), namely TLR2, TLR3, TLR4, TLR7, and TLR9 in AD and PD in human beings and a mouse model.

Alzheimer’s disease (AD) is a significant health concern with enormous social and economic impact globally. The gradual deterioration of cognitive functions and irreversible neuronal losses are primary features of the disease. Even after decades of research, most therapeutic options are merely symptomatic, and drugs in clinical practice present numerous side effects. Lack of effective diagnostic techniques prevents the early prognosis of disease, resulting in a gradual deterioration in the quality of life. Furthermore, the mechanism of cognitive impairment and AD pathophysiology is poorly understood. Microfluidics exploits different microscale properties of fluids to mimic environments on microfluidic chip-like devices. These miniature multichambered devices can be used to grow cells and 3D tissues in vitro, analyze cell-to-cell communication, decipher the roles of neural cells such as microglia, and gain insights into AD pathophysiology. This review focuses on the applications and impact of microfluidics on AD research. We discuss the technical challenges and possible solutions provided by this new cutting-edge technique to understand disease-associated pathways and mechanisms.

This article presents a novel three-dimensional constitutive modeling framework for residually stressed viscoelastic solids undergoing finite strains. Within the current of phenomenological approach, the constitutive relations are derived for a viscoelastic matrix whereas residual stresses are considered in the constitutive law in terms of a set of invariants. In particular, we analyze the bifurcation of a residually stressed viscoelastic solids using the finite element method (FEM). In-plane residual stresses are introduced in the constitutive relation that satisfy the balance of momentum. The implementation is discussed with regard to commercial finite element code Abaqus. Furthermore, the robustness of the proposed user material is illustrated emphasizing the dependence of bifurcation and viscoelastic parameters of tubes under torsion upon the residual stresses. The proposed formulation is also suitable for cord-rubber composite application like tires, airsprings, and soft tissues in biomechanics, among others, being such applications particular extensions to anisotropic materials.

A numerical procedure to analyze bifurcation and post-bifurcation of a finite deformation boundary-value problem for a residually-stressed elastic body is studied. In particular, the problem is the combined extension and inflation of a circular cylindrical tube subject to radial and circumferential residual stresses. The material model, given by a residual-stress dependent nonlinear elastic constitutive law in terms of invariants, is implemented in a finite element code. A numerical procedure to analyze the bifurcation and post-bifurcation of the finite deformation boundary-value problem at hand is developed based on the modified Riks method. The dependence of bifurcation and post-bifurcation behavior of tubes under the loading at hand on residual stresses is shown and compared with results when there is no residual stress. The finite deformation boundary-value problem is described mainly in terms of the inflation pressure, as well as the axial and azimuthal stretches of the tube. The dependence of these quantities on bifurcation is illustrated graphically for different values of the parameters (in dimensionless form) involved, in particular, the strength of the residual stress. It is found that bulging bifurcation is expected for sufficiently large values of the axial stretch. On the other hand, for small values of the axial stretch (close to the non-extended configuration), the onset of bifurcation is found to be the bending mode. Furthermore, for the latter case in subsequent motion, i.e. post-bifurcation, it is shown that bending triggers bulging as opposed to the situation in which bending is not allowed and the onset of bifurcation is associated with bulging. In addition, the bulge, or the abnormal enlargement, that is formed during post-bifurcation after the onset of bending bifurcation appears on one side of the tube showing an irregular shape which is consistent with the development of abdominal aortic aneurysms (AAA).

The computational modelling of fiber-reinforced structures is of prime importance for automotive products such as tires, airsprings or hoses and for biomechanical applications as is the case of arteries. In the first part of the paper, we outline the development of invariant-based constitutive models suitable for fiber-reinforced materials within the context of the phenomenological modeling approach. The polyconvex strain energy function for fiber composites is adopted from the literature and split into different contributions, which encompass the energy of the fiber, matrix, and the fiber-matrix interaction respectively. Experimental data from the literature are used to validate the model at hand. In the second part of the paper, the residual stress and damage effects are incorporated into the constitutive relation by exploiting an invariant-based representation and using an isotropic damage formulation, respectively. It is considered that residual stresses can arise in such fiber-matrix composites due to processes from different signature and affect the overall lifetime. The proposed formulation is implemented into commercial finite element code ABAQUS/Standard and is examined by means of several applications, showing a high robustness and reliability.