Epigenetic therapeutics attenuate kidney injury and fibrosis by restoring the expression of epigenetically reprogrammed fibrogenic genes and signaling pathways.

Kidney fibrosis is a commonly observed pathological condition during development of chronic kidney disease. Therapeutic options currently available are effective only in slowing the progression of kidney fibrosis and there is no cure for this disease. Aberrant expression and excessive accumulation of extracellular matrix (ECM) proteins in the peritubular space is a characteristic pathological feature of fibrotic kidney.

Modeling the Effects of Temperature in Enzymatic Biodiesel Synthesis of Jatropha Oil: An Optimal Control Approach.

Biodiesel, an alternative to diesel, is produced through the enzymatic transesterification of vegetable oil or animal fats. Enzymatic transesterification of oil is gaining more importance, as this method possesses no such disadvantages that are associated with the chemical process. Temperature is the most important factor in enzymatic transesterification for biodiesel synthesis.

A mathematical insight to control the disease psoriasis using mesenchymal stem cell transplantation with a biologic inhibitor.

Psoriasis is a chronic, non-contagious, immune-mediated skin disorder. Inflammation of the skin's surface is characterised by scaly white, red, or silvery spots that occur due to the hyper-proliferation of keratinocytes in the epidermal layer. Primarily, pharmaceutical drugs or immune therapy are used to treat psoriasis.

Insights of infected Schwann cells extinction and inherited randomness in a stochastic model of leprosy.

Investigating disease progression, transmission of infection and impacts of Multidrug Therapy (MDT) to inhibit demyelination in leprosy involves a certain amount of difficulty in terms of the in-built uncertain complicated and complex intracellular cell dynamical interactions. To tackle this scenario and to elucidate a more realistic, rationalistic approach of examining the infection mechanism and associated drug therapeutic interventions, we propose a four-dimensional ordinary differential equation-based model. Stochastic processes has been employed on this deterministic system by formulating the Kolmogorov forward equation introducing a transition state and the quasi-stationary distribution, exact distribution analysis have been investigated which allow us to estimate an expected time to extinction of the infected Schwann cells into the human body more prominently.

Motif-VI loop acts as a nucleotide valve in the West Nile Virus NS3 Helicase.

The Orthoflavivirus NS3 helicase (NS3h) is crucial in virus replication, representing a potential drug target for pathogenesis. NS3h utilizes nucleotide triphosphate (ATP) for hydrolysis energy to translocate on single-stranded nucleic acids, which is an important step in the unwinding of double-stranded nucleic acids. Intermediate states along the ATP hydrolysis cycle and conformational changes between these states, represent important yet difficult-to-identify targets for potential inhibitors.

Enhancement of Biodiesel Production via Ultrasound Technology: A Mathematical Study.

Biodiesel is one of the alternative renewable energy sources that has received a lot of attention since it is clean, green energy. Different sources can be used for the production of biodiesel, but the most appropriate and economical method relies on the transesterification of methanol with the nonedible vegetable oil from the fruit of the plant. Molar ratio, vessel diameter, catalyst concentration, and ultrasound all have a substantial influence on the synthesis of biodiesel by the transesterification process.

Role of ATP Hydrolysis and Product Release in the Translocation Mechanism of SARS-CoV-2 NSP13.

In response to the emergence of COVID-19, caused by SARS-CoV-2, there has been a growing interest in understanding the functional mechanisms of the viral proteins to aid in the development of new therapeutics. Nonstructural protein 13 (nsp13) helicase is an attractive target for antivirals because it is essential for viral replication and has a low mutation rate, yet the structural mechanisms by which this enzyme binds and hydrolyzes ATP to cause unidirectional RNA translocation remain elusive. Using Gaussian accelerated molecular dynamics (GaMD), we generated comprehensive conformational ensembles of all substrate states along the ATP-dependent cycle.

Epigallocatechin-3-gallate attenuates arsenic-induced fibrogenic changes in human kidney epithelial cells through reversal of epigenetic aberrations and antioxidant activities.

Renal fibrosis is a pathogenic intermediate stage of chronic kidney disease (CKD). Nephrotoxicants including arsenic can cause kidney fibrosis through induction of oxidative stress and epigenetic aberrations. Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, is known to have antioxidant and epigenetic modulation properties.

Motif-VI Loop Acts as a Nucleotide Valve in the West Nile Virus NS3 Helicase.

The flavivirus NS3 helicase (NS3h), a highly conserved protein, plays a pivotal role in virus replication and thus represents a potential drug target for flavivirus pathogenesis. NS3h utilizes nucleotide triphosphate, such as ATP, for hydrolysis energy (ATPase) to translocate on single-stranded nucleic acids, which is an important step in the unwinding of double-stranded nucleic acids. The intermediate states along the ATP binding and hydrolysis cycle, as well as the conformational changes between these states, represent important yet difficult-to-identify targets for potential inhibitors.

Estrogen-induced reactive oxygen species, through epigenetic reprogramming, causes increased growth in breast cancer cells.

Despite the progress made in cancer diagnosis and treatment, breast cancer remains the second leading cause of cancer-related death among the women. Exposure to elevated levels of endogenous estrogen or environmental estrogenic chemicals is an important risk factor for breast cancer. Estrogen metabolites and ROS generated during estrogen metabolism are known to play a critical role in estrogen carcinogenesis.

The Role of ATP Hydrolysis and Product Release in the Translocation Mechanism of SARS-CoV-2 NSP13.

In response to the emergence of COVID-19, caused by SARS-CoV-2, there has been a growing interest in understanding the functional mechanisms of the viral proteins to aid in the development of new therapeutics. Non-structural protein 13 (Nsp13) helicase is an attractive target for antivirals because it is essential for viral replication and has a low mutation rate; yet, the structural mechanisms by which this enzyme binds and hydrolyzes ATP to cause unidirectional RNA translocation remain elusive. Using Gaussian accelerated molecular dynamics (GaMD), we generated a comprehensive conformational ensemble of all substrate states along the ATP-dependent cycle.

Epigenetic mechanism of therapeutic resistance and potential of epigenetic therapeutics in chemorefractory prostate cancer.

Prostate cancer is the second leading cause of cancer death among men in the United States. Depending upon the histopathological subtypes of prostate cancers, various therapeutic options, such as androgen deprivation therapy (ADT), androgen receptor signaling inhibitors (ARSI), immunotherapy, and chemotherapy, are available to treat prostate cancer. While these therapeutics are effective in the initial stages during treatments, the tumors subsequently develop resistance to these therapies.

Critical observation of WHO recommended multidrug therapy on the disease leprosy through mathematical study.

Leprosy is a skin disease and it is characterized by a disorder of the peripheral nervous system which occurs due to the infection of Schwann cells. In this research article, we have formulated a four-dimensional ODE-based mathematical model which consists of the densities of healthy Schwann cells, infected Schwann cells, M. leprae bacteria, and the concentration of multidrug therapy (MDT).

Effects of External Perturbations on Protein Systems: A Microscopic View.

Protein folding can be viewed as the origami engineering of biology resulting from the long process of evolution. Even decades after its recognition, research efforts worldwide focus on demystifying molecular factors that underlie protein structure-function relationships; this is particularly relevant in the era of proteopathic disease. A complex co-occurrence of different physicochemical factors such as temperature, pressure, solvent, cosolvent, macromolecular crowding, confinement, and mutations that represent realistic biological environments are known to modulate the folding process and protein stability in unique ways.

Chronic coexposure to arsenic and estrogen potentiates genotoxic estrogen metabolic pathway and hypermethylation of DNA glycosylase MBD4 in human prostate epithelial cells.

Background: Previously we reported that arsenic and estrogen cause synergistic effects in the neoplastic transformation of human prostate epithelial cells. In addition to receptor-mediated pathways, DNA-reactive estrogen metabolites have also been shown to play a critical role in mutagenicity and carcinogenicity. Both estrogen and arsenic are known prostate carcinogens, however, the effect of coexposure to these two chemicals on genes involved in estrogen metabolism is not known.

Dynamical Manifestations of Supercooling in Amyloid Hydration.

The effect of extreme temperature on amyloidogenic species remains sparsely explored. In a recent study (, , , (10)), we employed exhaustive molecular dynamics simulations to explore the cold thermal response of a putative small amyloid oligomer and to elicit the role of solvent modulation. Herein, we investigate the dynamical response of the hydration waters of the oligomer within the supercooled states.

Hydroxy-Porphyrin as an Effective, Endogenous Molecular Clamp during Early Stages of Amyloid Fibrillization.

Amyloid fibril formation of proteins is of great concern in neurodegenerative disease and can be detrimental to the storage and stability of biologics. Recent evidence suggests that insulin fibril formation reduces the efficacy of type II diabetes management and may lead to several complications. To develop anti-amyloidogenic compounds of endogenous origin, we have utilized the hydrogen bond anchoring, π stacking ability of porphyrin, and investigated its role on the inhibition of insulin amyloid formation.

Hydration of a small protein under carbon nanotube confinement: Adsorbed substates induce selective separation of the dynamical response.

The co-involvement of biological molecules and nanomaterials has increasingly come to the fore in modern-day applications. While the "bio-nano" (BN) interface presents physico-chemical characteristics that are manifestly different from those observed in isotropic bulk conditions, the underlying molecular reasons remain little understood; this is especially true of anomalies in interfacial hydration. In this paper, we leverage atomistic simulations to study differential adsorption characteristics of a small protein on the inner (concave) surface of a single-walled carbon nanotube whose diameter exceeds dimensions conducive to single-file water movement.

Disulfide Reduction Allosterically Destabilizes the β-Ladder Subdomain Assembly within the NS1 Dimer of ZIKV.

The Zika virus (ZIKV) was responsible for a recent debilitating epidemic that till date has no cure. A potential way to reduce ZIKV virulence is to limit the action of the nonstructural proteins involved in its viral replication. One such protein, NS1, encoded as a monomer by the viral genome, plays a major role via symmetric oligomerization.

Stromal β-catenin activation impacts nephron progenitor differentiation in the developing kidney and may contribute to Wilms tumor.

Wilms' tumor (WT) morphologically resembles the embryonic kidney, consisting of blastema, epithelial and stromal components, suggesting tumors arise from the dysregulation of normal development. β-Catenin activation is observed in a significant proportion of WTs; however, much remains to be understood about how it contributes to tumorigenesis. Although activating β-catenin mutations are observed in both blastema and stromal components of WT, current models assume that activation in the blastemal lineage is causal.

A vivid cytokines interaction model on psoriasis with the effect of impulse biologic (TNF-α inhibitor) therapy.

Psoriasis is a chronic skin condition that produces plaques of condensed, scaling skin due to excessively rapid proliferation of keratinocytes. During the disease progression, keratinocyte proliferation is influenced by many immune cells and cytokines. This article deals with a five dimensional deterministic model, which has been derived using quasi-steady-state approximation for describing the dynamics of psoriasis in various cytokines environment.

Cosolvent Impurities in SWCNT Nanochannel Confinement: Length Dependence of Water Dynamics Investigated with Atomistic Simulations.

The advent of nanotechnology has seen a growing interest in the nature of fluid flow and transport under nanoconfinement. The present study leverages fully atomistic molecular dynamics (MD) simulations to study the effect of nanochannel length and intrusion of molecules of the organic solvent, hexafluoro-2-propanol (HFIP), on the dynamical characteristics of water within it. Favorable interactions of HFIP with the nanochannels comprised of single-walled carbon nanotubes traps them over time scales greater than 100 ns, and confinement confers small but distinguishable spatial redistribution between neighboring HFIP pairs.

Biological pest control using a model-based robust feedback.

Biological control is the artificial manipulation of natural enemies of a pest for its regulation to densities below a threshold for economic damage. The authors address the biological control of a class of pest population models using a model-based robust feedback approach. The proposed control framework is based on a recursive cascade control scheme exploiting the chained form of pest population models and the use of virtual inputs.

Mathematical insights on psoriasis regulation: Role of Th₁ and Th₂ cells.

Psoriasis is an autoimmune disorder, characterized by hyper-proli-feration of Keratinocytes for the abnormal activation of T Cells, Dendritic Cells (DCs) and cytokine signaling. Interaction of DCs and T Cells enable T Cell to differentiate into Type 1 (Th₁), Type 2 (Th₂) helper T Cell depending on cytokine release. Hyper-proliferation of Keratinocytes may occur due to over expression of pro-inflammatory cytokines secreted by Th₁-Cells viz.

Human immunodeficiency virus/acquired immune deficiency syndrome: Using drug from mathematical perceptive.

Entry of acquired immune deficiency syndrome virus into the host immune cell involves the participation of various components of host and viral cell unit. These components may be categorized as attachment of the viral surface envelope protein subunit, gp120, to the CD4(+) receptor and chemokine coreceptors, CCR5 and CXCR4, present on T cell surface. The viral fusion protein, gp41, the second cleaved subunit of Env undergoes reconfiguration and the membrane fusion reaction itself.