No abstract

A number of nucleotide residues in ribosomal RNA undergo specific posttranscriptional modification. The roles of most modifications are unclear, but their clustering in the functionallyimportant regions of rRNA suggest that they might either directly affect the activity or assembly of the ribosome or modulate its interactions with ligands. Of the 25 modified nucleotides in E. coli 23S rRNA, 14 are located in the peptidyl transferase center, the main antibiotic target in the large ribosomal subunit. Since nucleotide modifications have been closely associated with both antibiotic sensitivity and antibiotic resistance, the loss of some of these posttranscriptional modifications may affect the susceptibility of bacteria to antibiotics. We investigated the antibiotic sensitivity of E. coli cells in which the genes of eight rRNA modifying enzymes targeting the PTC were individually inactivated. The lack of pseudouridine at position 2504 of 23S rRNA was found to significantly increase the susceptibility of bacteria to peptidyl transferase inhibitors. Therefore, this indigenous posttranscriptional modification may have evolved as an intrinsic resistance mechanism protecting bacteria against natural antibiotics.Posttranscriptional modifications in rRNA are ubiquitous. However, the functional significance of most of them remains obscure. Acquisition and maintenance through the course of evolution of a number of genes dedicated to rRNA modification in spite of the associated energetic and metabolic cost argue that the modified nucleotides in rRNA render competitive benefits for the species. Clustering of the modified nucleotides in the functional centers of the ribosome hint that some of them may help to fine-tune ribosome functions. Indeed, inactivation of certain modification enzymes was shown to either decrease the efficiency of protein synthesis or negatively affect ribosome assembly 1 -5 . Yet, in most cases, the lack of individual posttranscriptional modifications only marginally affects cell growth 6; 7 .The ribosome is one of the evolutionarily-preferred antibiotic targets. A large variety of natural antibiotics of microbial origin bind to the ribosomes of sensitive organisms and inhibit protein synthesis thereby providing competitive advantage to the antibiotic producers. One of the common ways in which antibiotic producers avoid suicide is by expressing HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author Manuscript specific methyltransferase enzymes which modify rRNA residues in the drug target site, and thus prevent antibiotic binding to the ribosome 8; 9 . Acquisition of such genes by pathogens is one of the major causes of clinical resistance to a number of antibacterial drugs. However, not only acquisition of new rRNA modifications, but the lack of natural modifications may affect susceptibility of cells to antibiotics. In a few well-documented cases, the lack of natural modifications was shown to render cells resistant to specific antibiotics 10 -12 .Most of the antibioti...

Azithromycin (AZM) is a macrolide antibiotic used for the treatment of various bacterial infections. The drug is known to have low oral bioavailability (37%) which may be attributed to its relatively high molecular weight, low solubility, dissolution rate, and incomplete intestinal absorption. To overcome these drawbacks, liquid (L) and solid (S) self-emulsifying drug delivery systems (SEDDs) of AZM were developed and optimized. Eight different pseudo-ternary diagrams were constructed based on the drug solubility and the emulsification studies in various SEDDs excipients at different surfactant to co-surfactant (Smix) ratios. Droplet size (DS) < 150 nm, dispersity (Đ) ≤ 0.7, and transmittance (T)% > 85 in three diluents of distilled water (DW), 0.1 mM HCl, and simulated intestinal fluids (SIF) were considered as the selection criteria. The final formulations of L-SEDDs (L-F1(H)), and S-SEDDs (S-F1(H)) were able to meet the selection requirements. Both formulations were proven to be cytocompatible and able to open up the cellular epithelial tight junctions (TJ). The drug dissolution studies showed that after 5 min > 90% and 52.22% of the AZM was released from liquid and solid SEDDs formulations in DW, respectively, compared to 11.27% of the pure AZM, suggesting the developed SEDDs may enhance the oral delivery of the drug. The formulations were stable at refrigerator storage conditions.

A simple, economic, rapid, reliable, and stability-indicating high-performance liquid chromatography (HPLC) method has been developed and validated for the simultaneous determination of paracetamol (PCM) and caffeine (CF) in solid dosage form. The chromatographic separations were achieved with a Waters Symmetry W C18 column (5 μm, 4.6 × 150 mm), using a mixture of methanol and water (40:60, v/v) as a mobile phase, under isocratic elution mode with a flow rate of 0.8 mL/min, and ultraviolet (UV) detection was set at 264 nm. The oven temperature for the column was set and maintained at 35 °C. The method was validated according to International Conference on Harmonization (ICH) guidelines, and it demonstrated excellent linearity, with a correlation coefficient of 1 and 0.9999 for PCM and CF, respectively, over the concentration ranges of 15-300 μg/mL (PCM) and 2.5-50 μg/mL (CF). The retention time (t R ) was found to be 2.6 ± 0.001 and 3.5 ± 0.002 min for PCM and CF, respectively. Extensive stress degradation studies were conducted by subjecting the analytes to various stress conditions of acidic and alkaline hydrolysis as well as oxidative, photolytic, and heat degradations. The method was found to efficiently separate the analytes' peaks from that of the degradation products, without any variation in their retention times. The relative standard deviation (RSD) values of all recoveries for PCM and CF were less than 1.3%. The method was found to be suitable for routine analysis of PCM and CF in pharmaceutical dosage form.

Curcuma aromatica Salisb. (C. aromatica) is commonly known as wild turmeric. Curcuma aromatica is an essential herbal plant and it has been extensively used in traditional medicine for centuries. It has been used for the treatment of gastrointestinal ailments, arthritic pain, inflammatory conditions, wounds, skin infections, and insect bites. This article aims to review the phytochemical and pharmacological aspects of C. aromatica and to provide a guide and insight for further studies. Electronic repositories, including Web of Science, Google Scholar, ProQuest, Science Direct, Scopus, and PubMed, were searched until December 2019 to identify studies relating to C. aromatica. A systematic analysis of the literature on pharmacognostical, physicochemical, and nutritional contents, bioactive compounds, and biological activities of C. aromatica was carried out, and ideas for future studies were also coined. A total of 157 articles concerning in vitro or in vivo (or both) researches on C. aromatica have been evaluated. Analyses of the data showed that C. aromatica consists of various classes of compounds, including alkaloids, flavonoids, curcuminoids, tannins, and terpenoids, that formed the bases of its pharmacological activities. The reviewed data also revealed that C. aromatica possessed the pharmacological effect of anticancer, antidiabetic, antioxidant, anti-inflammatory, antimicrobial, antitussive, antiepileptic, analgesic, wound healing, and insect repellent activities. This review has systematically compiled and summarized the literature related to the nutritional values and bioactive compounds, as well as the biological activities of C. aromatica. To the best of our knowledge, this is the most comprehensive review reported on C. aromatica.

It is undeniable that many patients worldwide suffer from various types of wounds, especially from chronic wounds. The complex and intricate process of wound healing has a severe impact on the patient's quality of life as well as causing an economic burden on healthcare institutions. Although various new therapies have become available for treating patients with acute and chronic wounds for the past decade, the available therapies are often expensive or accompanied by undesirable side effects. Hence, the discovery of a new arsenal for wound healing remains a hot topic of research. Recently, plants or herbs and their derivatives have garnered significant attention as a source of therapeutic agents to treat wounds. This is because plants provide a rich reservoir of phytochemicals that could potentially become effective and affordable therapeutic agents. Thus, the present review attempted to outline wound healing mechanisms and analysed some renowned medicinal plants with potential wound healing properties from the existing literature from various electronic databases. This review also sheds light on the plant's underlying molecular mechanisms and, wherever available, acknowledges the biologically active substances found in these plants.

Background The aim of the study was to evaluate the suitability of triclosan (TCS) and flurbiprofen (FLB) with poly-ε-caprolactone (PCL), chitosan (CS), and Kolliphor® P188 (KP) for possible application in the design of nano-formulations. Results Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and scanning electron microscopy (SEM) revealed the physical characteristics of the various sample compositions without any apparent interaction. The Fourier transform infrared spectroscopy (FTIR)’s spectra of the physical mixtures showed their characteristic absorption bands with broadening and overlapping of bands in some instances, but no appearance of new bands was observed. Conclusion The study revealed the physical form stability of the evaluated components after the storage period and lack of definite pharmaceutical incompatibility between them. Thus, the selected drugs and excipients could be used for the development of pharmaceutical nano-formulations.

An increase of crystallinity in a post humidity treated SD did not exert detrimental effect to their dissolution profiles. A more stabilized system with a preferable enhanced dissolution rate was obtained by exposing the SD to a post processing humidity treatment.