Multiple drug-resistant bacteria are a severe and growing public health concern. Because relatively few antibiotics have been approved over recent years and because of the inability of existing ...antibiotics to combat bacterial infections fully, demand for unconventional biocides is intense. Metallic nanoparticles (NPs) offer a novel potential means of fighting bacteria. Although metallic NPs exert their effects through membrane protein damage, superoxide radicals and the generation of ions that interfere with the cell granules leading to the formation of condensed particles, their antimicrobial potential, and mechanisms of action are still debated. This article discusses the action of metallic NPs as antibacterial agents, their mechanism of action, and their effect on bacterial drug resistance. Based on encouraging data about the antibacterial effects of NP/antibiotic combinations, we propose that this concept be thoroughly researched to identify means of combating drug-resistant bacteria.
Heavy metals, which have widespread environmental distribution and originate from natural and anthropogenic sources, are common environmental pollutants. In recent decades, their contamination has ...increased dramatically because of continuous discharge in sewage and untreated industrial effluents. Because they are non-degradable, they persist in the environment; accordingly, they have received a great deal of attention owing to their potential health and environmental risks. Although the toxic effects of metals depend on the forms and routes of exposure, interruptions of intracellular homeostasis include damage to lipids, proteins, enzymes and DNA via the production of free radicals. Following exposure to heavy metals, their metabolism and subsequent excretion from the body depends on the presence of antioxidants (glutathione, α-tocopherol, ascorbate, etc.) associated with the quenching of free radicals by suspending the activity of enzymes (catalase, peroxidase, and superoxide dismutase). Therefore, this review was written to provide a deep understanding of the mechanisms involved in eliciting their toxicity in order to highlight the necessity for development of strategies to decrease exposure to these metals, as well as to identify substances that contribute significantly to overcome their hazardous effects within the body of living organisms.
Advanced glycation end products (AGEs) culminate from the non-enzymatic reaction between a free carbonyl group of a reducing sugar and free amino group of proteins. 3-deoxyglucosone (3-DG) is one of ...the dicarbonyl species that rapidly forms several protein-AGE complexes that are believed to be involved in the pathogenesis of several diseases, particularly diabetic complications. In this study, the generation of AGEs (Nε-carboxymethyl lysine and pentosidine) by 3-DG in H1 histone protein was characterized by evaluating extent of side chain modification (lysine and arginine) and formation of Amadori products as well as carbonyl contents using several physicochemical techniques. Results strongly suggested that 3-DG is a potent glycating agent that forms various intermediates and AGEs during glycation reactions and affects the secondary structure of the H1 protein. Structural changes and AGE formation may influence the function of H1 histone and compromise chromatin structures in cases of secondary diabetic complications.
Over the last few decades, computer-aided drug design has emerged as a powerful technique playing a crucial role in the development of new drug molecules. Structure-based drug design and ligand-based ...drug design are two methods commonly used in computer-aided drug design. In this article, we discuss the theory behind both methods, as well as their successful applications and limitations. To accomplish this, we reviewed structure based and ligand based virtual screening processes. Molecular dynamics simulation, which has become one of the most influential tool for prediction of the conformation of small molecules and changes in their conformation within the biological target, has also been taken into account. Finally, we discuss the principles and concepts of molecular docking, pharmacophores and other methods used in computer-aided drug design.
Graft and dendronized polymers have attracted much attention in the polymer community, and there have been significant efforts to develop better synthetic methods. Herein, we report the highly ...efficient synthesis of graft and dendronized polymers by using Cu-catalyzed multicomponent polymerization (MCP). Based on diversity-oriented synthesis, we prepared a library of various graft and dendronized polymers from combinations of three types of monomers (mono-functionalized alkynes, bis-sulfonyl azides, and diamines/diols) that are bench stable and readily accessible. After reaction optimization, 54 samples of high-molecular-weight graft and dendronized polymers were prepared, the MCP method allowing simultaneous manipulation of the structures of both the main chains and the side chains. Moreover, because of the severe steric hindrance of the side chains, these polymers adopted extended conformations, as shown by the large shape parameter in solution. Also, the extended morphology of the single polymer chains was directly visualized by atomic force microscopy and transmission electron microscopy in the solid state. Most importantly, this diversity-oriented polymerization became possible because of highly step-economical and efficient one-step MCP, paving the way toward the easily tunable synthesis of graft and dendronized polymers.
Alzheimer's disease (AD) is the most common type of dementia and usually manifests as diminished episodic memory and cognitive functions. Caspases are crucial mediators of neuronal death in a number ...of neurodegenerative diseases, and caspase 8 is considered a major therapeutic target in the context of AD. In the present study, we performed a virtual screening of 200 natural compounds by molecular docking with respect to their abilities to bind with caspase 8. Among them, rutaecarpine was found to have the highest (negative) binding energy (-6.5 kcal/mol) and was further subjected to molecular dynamics (MD) simulation analysis. Caspase 8 was determined to interact with rutaecarpine through five amino acid residues, specifically Thr337, Lys353, Val354, Phe355, and Phe356, and two hydrogen bonds (ligand: H35-A: LYS353:O and A:PHE355: N-ligand: N5). Furthermore, a 50 ns MD simulation was conducted to optimize the interaction, to predict complex flexibility, and to investigate the stability of the caspase 8-rutaecarpine complex, which appeared to be quite stable. The obtained results propose that rutaecarpine could be a lead compound that bears remarkable anti-Alzheimer's potential against caspase 8.
Skeletal muscle (SM) is a highly plastic and dynamic tissue of the body and is largely responsible for body maintenance. SM is primarily responsible for body balance, movement, postural support, ...thermogenesis, and blood glucose homeostasis. SM regeneration depends on the activation of muscle satellite (stem) cells (MSCs) under the regulation of several muscle regulatory factors that regulate myogenesis. Bibliometric analysis involves the quantitative and qualitative assessments of research and scientific progress that provides researchers access to recent publications, research directions, and thus generates ideas that can be implemented to guide future research. In this analysis, the Web of Science database was searched for articles using the search term “skeletal muscle AND myogenesis AND muscle satellite cell”, and 1777 articles (original research/review articles) published from the year 1997 to June 2023 were retrieved. After applying several other exclusion and inclusion criteria, 129 articles were considered for analysis. Types of research, keywords, journals, authors, years, institutions, funding agencies, and average annual citations were analyzed. Muscle regeneration, satellite cell, and myogenesis were often used keywords and exhibited increasing trends in research articles over the decades. Some journals were found to strongly support research publications with high impact factors and citation scores. This study aimed to examine research ideas and growth in the skeletal muscle related field for atrophy and aging improvement.
Background: Neurodegenerative disorders (NDs) are diverse group of disorders characterized
by escalating loss of neurons (structural and functional). The development of potential
therapeutics for NDs ...presents an important challenge, as traditional treatments are inefficient and
usually are unable to stop or retard the process of neurodegeneration. Computer-Aided Drug Design
(CADD) has emerged as an efficient means of developing candidate drugs for the treatment of
many disease types. Applications of CADD approach to drug discovery are progressing day by day.
The recent tendency in drug design is to rationally design potent therapeutics with multi-targeting
effects, higher efficacies, and fewer side effects, especially in terms of toxicity.
Methods: A wide literature search was performed for writing this review. An updated view on different
types of NDs, their effect on human population and a brief introduction to CADD, various
approaches involved in this technique, ranging from structural-based to ligand-based drug design
has been discussed. The successful application of CADD approaches for the treatment of neurodegenerative
disorders is also included in this review.
Results: In this review, we have briefly described about CADD and its use in the development of
the therapeutic drug candidates against NDs. The successful applications, limitations and future
prospects of this approach have also been discussed.
Conclusion: CADD can assist researchers studying interactions between drugs and receptors. We
believe this review will be helpful for better understanding of CADD and its applications towards
the discovery of new drug candidates against various fatal NDs.
Cyclobenzaprine hydrochloride (CBH) is a well-known muscle relaxant that is widely used to relieve muscle spasms and other pain associated with acute musculoskeletal conditions. In this study, we ...elucidated the binding characteristics of this muscle relaxant to human serum albumin (HSA). From a pharmaceutical and biochemical viewpoint, insight into the structure, functions, dynamics, and features of HSA-CBH complex holds great importance. The binding of CBH with this major circulatory transport protein was studied using a combination of biophysical approaches such as UV-VIS absorption, fluorescence quenching, and circular dichroism (CD) spectroscopy. Various
techniques, molecular docking and molecular dynamics, were also used to gain deeper insight into the binding. A reduction in the fluorescence intensities of HSA-CBH complex with a constant increase in temperature, revealed the static mode of protein fluorescence quenching upon CBH addition, which confirmed the formation of the HSA-CBH ground state complex. The alteration in the UV-VIS and far-UV CD spectrum indicated changes in both secondary and tertiary structures of HSA upon binding of CBH, further proving CBH binding to HSA. The analysis of thermodynamic parameters ∆H° and ∆S° showed that binding of CBH to HSA was dominated by intermolecular hydrophobic forces. The results of the molecular docking and molecular dynamics simulation studies also confirmed the stability of the complex and supported the experimental results.
The skeletal muscle (SM) is the largest organ in the body and has tremendous regenerative power due to its myogenic stem cell population. Myostatin (MSTN), a protein produced by SM, is released into ...the bloodstream and is responsible for age-related reduced muscle fiber development. The objective of this study was to identify the natural compounds that inhibit MSTN with therapeutic potential for the management of age-related disorders, specifically muscle atrophy and sarcopenia. Sequential screening of 2000 natural compounds was performed, and dithymoquinone (DTQ) was found to inhibit MSTN with a binding free energy of −7.40 kcal/mol. Furthermore, the docking results showed that DTQ reduced the binding interaction between MSTN and its receptor, activin receptor type-2B (ActR2B). The global energy of MSTN-ActR2B was found to be reduced from −47.75 to −40.45 by DTQ. The stability of the DTQ–MSTN complex was subjected to a molecular dynamics analysis for up to 100 ns to check the stability of the complex using RMSD, RMSF, Rg, SASA, and H-bond number. The complex was found to be stable after 10 ns to the end of the simulation. These results suggest that DTQ blocks MSTN signaling through ActR2B and that it has potential use as a muscle growth-promoting agent during the aging process.
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