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.
Skeletal muscle (SM) comprises around 40% of total body weight and is among the most important plastic tissues, as it supports skeletal development, controls body temperature, and manages glucose ...levels. Extracellular matrix (ECM) maintains the integrity of SM, enables biochemical signaling, provides structural support, and plays a vital role during myogenesis. Several human diseases are coupled with dysfunctions of the ECM, and several ECM components are involved in disease pathologies that affect almost all organ systems. Thus, mutations in ECM genes that encode proteins and their transmembrane receptors can result in diverse SM diseases, a large proportion of which are types of fibrosis and muscular dystrophy. In this review, we present major ECM components of SMs related to muscle-associated diseases, and discuss two major ECM myopathies, namely, collagen myopathy and laminin myopathies, and their therapeutic managements. A comprehensive understanding of the mechanisms underlying these ECM-related myopathies would undoubtedly aid the discovery of novel treatments for these devastating diseases.
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.
Skeletal muscle (SM) plays a vital role in energy and glucose metabolism by regulating insulin sensitivity, glucose uptake, and blood glucose homeostasis. Impaired SM metabolism is strongly linked to ...several diseases, particularly type 2 diabetes (T2D). Insulin resistance in SM may result from the impaired activities of insulin receptor tyrosine kinase, insulin receptor substrate 1, phosphoinositide 3-kinase, and AKT pathways. This review briefly discusses SM myogenesis and the critical roles that SM plays in insulin resistance and T2D. The pharmacological targets of T2D which are associated with SM metabolism, such as DPP4, PTB1B, SGLT, PPARγ, and GLP-1R, and their potential modulators/inhibitors, especially natural compounds, are discussed in detail. This review highlights the significance of SM in metabolic disorders and the therapeutic potential of natural compounds in targeting SM-associated T2D targets. It may provide novel insights for the future development of anti-diabetic drug therapies. We believe that scientists working on T2D therapies will benefit from this review by enhancing their knowledge and updating their understanding of the subject.
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•Impaired SM metabolism is linked to metabolic disorders such as T2D.•Enhancing insulin sensitivity is likely to improve metabolic health.•Natural products are utilized for the treatment of metabolic disorders.•Targets of T2D associated with SM metabolism are DPP4, PTB1B, SGLT, PPARγ, and GLP1-R.
Neurodegeneration is a prevalent and one of the emerging reasons for morbidity, mortality, and cognitive impairment in aging. Dementia is one of such conditions of neurodegeneration, partially ...manageable, irreversible, and worsens over time. This review is focused on biological and psychosocial risk factors associated with Alzheimer’s and Parkinson’s diseases, highlighting the value of cognitive decline. We further emphasized on current therapeutic strategies from pharmacological and non-pharmacological perspectives focusing on their effects on cognitive impairment, protein aggregation, tau pathology, and improving the quality of life. Deeper mechanistic insights into the multifactorial neurodegeneration could offer the design and development of promising diagnostic and therapeutic strategies.
Myostatin (MSTN), a negative regulator of muscle mass, is reported to be increased in conditions linked with muscle atrophy, sarcopenia, and other muscle-related diseases. Most pharmacologic ...approaches that treat muscle disorders are ineffective, emphasizing the emergence of MSTN inhibition. In this study, we used computational screening to uncover natural small bioactive inhibitors from the Traditional Chinese Medicine database (~38,000 compounds) for the MSTN protein. Potential ligands were screened, based on binding affinity (150), physicochemical (53) and ADMET properties (17). We found two hits (ZINC85592908 and ZINC85511481) with high binding affinity and specificity, and their binding patterns with MSTN protein. In addition, molecular dynamic simulations were run on each complex to better understand the interaction mechanism of MSTN with the control (curcumin) and the hit compounds (ZINC85592908 and ZINC85511481). We determined that the hits bind to the active pocket site (Helix region) and trigger conformational changes in the MSTN protein. Since the stability of the ZINC85592908 compound was greater than the MSTN control, we believe that ZINC85592908 has therapeutic potential against the MSTN protein and may hinder downstream singling by inhibiting the MSTN protein and increasing myogenesis in the skeletal muscle tissues.
Myostatin (MSTN) is a well-reported negative regulator of muscle growth and a member of the transforming growth factor (TGF) family. MSTN has important functions in skeletal muscle (SM), and its ...crucial involvement in several disorders has made it an important therapeutic target. Several strategies based on the use of natural compounds to inhibitory peptides are being used to inhibit the activity of MSTN. This review delivers an overview of the current state of knowledge about SM and myogenesis with particular emphasis on the structural characteristics and regulatory functions of MSTN during myogenesis and its involvements in various muscle related disorders. In addition, we review the diverse approaches used to inhibit the activity of MSTN, especially
in silico
approaches to the screening of natural compounds and the design of novel short peptides derived from proteins that typically interact with MSTN.
Licochalcone B (LicB), a chalcone derived from Glycyrrhiza uralensis and Glycyrrhiza glabra, has received considerable attention due to its diverse pharmacological properties. Accumulated data ...indicates that LicB has pharmacological effects that include anti-cancer, hepatoprotective, anti-inflammatory, and neuroprotective properties. The action mechanism of LicB has been linked to several molecular targets, such as phosphoinositide 3-kinase/Akt/mammalian target of rapamycin, p53, nuclear factor-κB, and p38, and the involvements of caspases, apoptosis, mitogen-activated protein kinase-associated inflammatory pathways, and anti-inflammatory nuclear factor erythroid 2–related factor 2 signaling pathways highlight the multifaceted therapeutic potential of LicB. This review systematically updates recent findings regarding the pharmacological effects of LicB, and the mechanistic pathways involved, and highlights the potential use of LicB as a promising lead compound for drug discovery.
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