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.
Tolperisone hydrochloride (TH) has muscle relaxant activity and has been widely used for several years in clinical practice to treat pathologically high skeletal muscle tone (spasticity) and related pains. The current study was designed to explore the binding efficacy of TH with human serum albumin (HSA) using multispectrscopic, calorimetric approach, FRET, esterase-like activity, and a molecular docking method. A reduction in fluorescence emission at 340 nm of HSA was attributed to fluorescence quenching by TH via a static quenching type. Binding constants ( K) were evaluated at different temperatures, and obtained K values were ∼10 M, which demonstrated moderately strong affinity of TH for HSA. A calculated negative Δ G° value indicated spontaneous binding of TH to HSA. Far-UV CD spectroscopy revealed that the α-helix content was increased after TH binding. The binding distance between donor and acceptor was calculated to be 2.11 nm based on Förster's resonance energy transfer theory. ITC results revealed TH interacted with HSA via hydrophobic interactions and hydrogen bonding. The thermal stability of HSA was studied using DSC, and results showed that in the presence of TH the structure of HSA was significantly more thermostable. The esterase-like activity of HSA showed fixed V and increased K suggesting that TH binds with HSA in a competitive manner. Furthermore, molecular docking results revealed TH binds in the cavity of HSA, that is, subdomain IIA (Sudlow site I), and that it hydrogen bonds with K199 and H242 of HSA. Binding studies of drugs with HSA are potentially useful for elucidating chemico-biological interactions that can be utilized in the drug design, pharmaceutical, pharmacology, and biochemistry fields. This extensive study provides additional insight of ligand binding and structural changes induced in HSA relevant to the biological activity of HSA in vivo.
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.
The skeletal muscle provides movement and support to the skeleton, controls body temperature, and regulates the glucose level within the body. This is the core tissue of insulin-mediated glucose uptake via glucose transporter type 4 (GLUT4). The extracellular matrix (ECM) provides integrity and biochemical signals and plays an important role in myogenesis. In addition, it undergoes remodeling upon injury and/or repair, which is also related to insulin resistance (IR), a major cause of type 2 diabetes (T2DM). Altered signaling of integrin and ECM remodeling in diet-induced obesity is associated with IR. This review highlights the interweaving relationship between the ECM, IR, and skeletal muscle. In addition, the importance of the ECM in muscle integrity as well as cellular functions is explored. IR and skeletal muscle ECM remodeling has been discussed in clinical and nonclinical aspects. Furthermore, this review considers the role of ECM glycation and its effects on skeletal muscle homeostasis, concentrating on advanced glycation end products (AGEs) as an important risk factor for the development of IR. Understanding this complex interplay between the ECM, muscle, and IR may improve knowledge and help develop new ideas for novel therapeutics for several IR-associated myopathies and diabetes.
Skeletal muscle is an essential tissue that attaches to bones and facilitates body movements. Insulin-like growth factor-1 (IGF-1) is a hormone found in blood that plays an important role in skeletal myogenesis and is importantly associated with muscle mass entity, strength development, and degeneration and increases the proliferative capacity of muscle satellite cells (MSCs). IGF-1R is an IGF-1 receptor with a transmembrane location that activates PI3K/Akt signaling and possesses tyrosine kinase activity, and its expression is significant in terms of myoblast proliferation and normal muscle mass maintenance. IGF-1 synthesis is elevated in MSCs of injured muscles and stimulates MSCs proliferation and myogenic differentiation. Mechanical loading also affects skeletal muscle production by IGF-1, and low IGF-1 levels are associated with low handgrip strength and poor physical performance. IGF-1 is potentially useful in the management of Duchenne muscular dystrophy, muscle atrophy, and promotes neurite development. This review highlights the role of IGF-1 in skeletal muscle, its importance during myogenesis, and its involvement in different disease conditions.
Background. This retrospective analysis examines the frequency, distribution, and the pattern of disease progression of bone metastasis in patients treated for cervical cancer and the use and results of palliative intent radiation therapy. Methods. Charts, films, and other available records were reviewed for the 41 patients with bone metastasis of the 496 patients with invasive cervical cancer treated at the Gershenson Radiation Oncology Center, Detroit, Michigan, from 1980 through 1989. Results. Several patterns of bone metastasis were observed: (1) direct extension into bone from the parametrial extensions of the primary or recurrent pelvic tumor, (2) direct extension into bone from parenchymal metastasis to distant lymph nodes or lung, (3) regional hematogenous metastasis compatible with Batson's venous plexus distribution, and (4) systemic hematogenous metastasis to distant bones. Eighty percent of the patients were irradiated, and of those, 70% experienced pain relief. Conclusions. Bone metastasis in patients with cervical cancer is an infrequent but significant occurrence with associated severe dysfunction, other signs of local and distant failure, and short life expectancy. Radiation therapy provides moderate palliation for treatable patients.
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