Cirrhosis is a severe form of liver fibrosis that results in the irreversible replacement of liver tissue with scar tissue in the liver. Environmental toxicity, infections, metabolic causes, or other genetic factors including autoimmune hepatitis can lead to chronic liver injury and can result in inflammation and fibrosis. This activates myofibroblasts to secrete ECM proteins, resulting in the formation of fibrous scars on the liver. Fibrosis regression is possible through the removal of pathophysiological causes as well as the elimination of activated myofibroblasts, resulting in the reabsorption of the scar tissue. To date, a wide range of antifibrotic therapies has been tried and tested, with varying degrees of success. These therapies include the use of growth factors, cytokines, miRNAs, monoclonal antibodies, stem-cell-based approaches, and other approaches that target the ECM. The positive results of preclinical and clinical studies raise the prospect of a viable alternative to liver transplantation in the near future. The present review provides a synopsis of recent antifibrotic treatment modalities for the treatment of liver cirrhosis, as well as a brief summary of clinical trials that have been conducted to date.
Antibiotic resistance in Pseudomonas aeruginosa remains one of the most challenging phenomena of everyday medical science. The universal spread of high-risk clones of multidrug-resistant/extensively drug-resistant (MDR/XDR) clinical P. aeruginosa has become a public health threat. The P. aeruginosa bacteria exhibits remarkable genome plasticity that utilizes highly acquired and intrinsic resistance mechanisms to counter most antibiotic challenges. In addition, the adaptive antibiotic resistance of P. aeruginosa, including biofilm-mediated resistance and the formation of multidrug-tolerant persisted cells, are accountable for recalcitrance and relapse of infections. We highlighted the AMR mechanism considering the most common pathogen P. aeruginosa, its clinical impact, epidemiology, and save our souls (SOS)-mediated resistance. We further discussed the current therapeutic options against MDR/XDR P. aeruginosa infections, and described those treatment options in clinical practice. Finally, other therapeutic strategies, such as bacteriophage-based therapy and antimicrobial peptides, were described with clinical relevance.
Pseudomonas aeruginosa is an adaptable bacterial pathogen that infects a variety of organs, including the respiratory tract, vascular system, urinary tract, and central nervous system, causing significant morbidity and mortality. As the primary goal of this study, we wanted to determine how pigment color production differed between clinical strains of P. aeruginosa, and whether or not that variation was associated with multidrug resistance or the ability to form biofilms. We screened in total 30.1% of yellow, 39.8% green and 30.1% of no pigment-producing P. aeruginosa strains from a total of 143 various clinical isolates. Yellow pigment-producing strains presented significant resistance to antibiotics groups, including β-lactam (91.5%), aminoglycosides (70.5%), and carbapenems (51.9%) compared to green and non-pigmented strains. Notably, 16.3% of yellow pigment-producing strains were resistant to colistin which is used as a last-resort treatment for multidrug-resistant bacteria, whereas only 2.3% of non-pigmented and 1.8% of green pigmented strains were resistant to colistin. Aside from that, yellow pigment-producing strains were frequent producers of enzymes belonging to the lactamase family, including ESBL (55.6%), MBL (55.6%), and AmpC (50%). Compared to the green groups (7.14%) and non-pigmented groups (28.5%), they had a higher frequency of efflux positive groups (64.2%). Notably, when compared to non-pigmented groups, green pigment-producing strains also displayed antibiotic susceptibility behavior similar to yellow pigment-producing strains. The majority of yellow pigment-producing strains outperformed the green and non-pigmented strains in terms of MIC levels when compared to the other two groups of strains. Despite the fact that previous studies have demonstrated a direct correlation between multidrug resistance behaviors and biofilm production, no such statistically significant association between pigment and biofilm formation was found in our investigation. Our research has demonstrated that the correlation of bacterial pigments on their susceptibility to antimicrobial agents. Yellow pigment-producing P. aeruginosa strains posed a significant problem due to the lack of alternative agents against such transformed strains, which may be associated with the development of multidrug resistance. Graphical Abstract
Alginate is a polysaccharide that has found numerous applications in the domain of pharmaceutical science, paper and textile industry, food industry, dental applications, welding roads, mucoadhesive properties, scaffolding, biomedical and engineering due to its cost-effective nature, film forming ability, gelling, biocompatibility, biodegradability, nontoxic, non-immunogenic, readily availability, antimicrobial nature. Hydrogels of alginates play a crucial role in well-controlled or sustained release drug delivery, wound healing, and tissue engineering. This book chapter will provide a detailed overview of Alginate and its applications. To the best of our knowledge there no such type of informative data is available on Alginate and its relation with drug susceptibility. Here we more focused on the antibiotic capability of Alginate and its association with bacterial resistance.
Microbial biofilms are intricate communities that pose significant challenges in clinical and microbiological settings due to their resistance to antibiotics and immune responses. Advanced microscopy techniques, such as scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and fluorescence microscopy, are often employed to visualize and differentiate between these biofilms. However, these methods are not feasible in all laboratories because of their high cost and complexity. In contrast, simpler techniques like crystal violet and Congo red staining fail to differentiate bacterial cells from the biofilm matrix. This study introduces a novel dual-staining method using Maneval’s stain for microbial biofilm detection and differentiation. This simple, cost-effective method requires only basic equipment and minimal reagents, making it suitable for routine use across various settings. We applied the dual-staining method to various microbial species, including Staphylococcus aureus, Enterococcus faecalis, Candida albicans, Escherichia coli, and Pseudomonas aeruginosa. When compared with the microtiter plate assay, results showed strong agreement, with the dual-staining method effectively differentiating between bacterial cells and the surrounding biofilm matrix, displaying a distinctive blue polysaccharide layer surrounding the magenta‒red bacterial cells. This technique offers a viable alternative to more expensive and complex biofilm detection methods, with potential applications in clinical diagnostics and biofilm research.