Infectious disorders drug targets最新文献

Infectious disorders known as Neglected Tropical Diseases (NTDs) initially affect the world's underprivileged citizens. They have been disregarded for many years, first as a result of a general indifference to such a developing world and, more recently, as an outcome of the intense attention on AIDS, TB, and malaria. Tropical diseases mostly affect the region where health and hygiene are sacrificed, and most of the population lacks access to sufficient food and living resources. WHO has drafted and released the directions for regulation, prevention, and successful eradication of NTDs as per the revised roadmap of 2021-2030. This shifts from vertical disease programs to integrated cross-cutting methods. In the current work, we have provided comprehensive information on various aspects of neglected tropical diseases, including the clinical management of NTDs. This encompasses the causative agent of the diseases, their symptoms, pathogenesis, diagnosis, treatment, prognosis, and epidemiological perspective of major NTDs. This review will shed light on several perspectives of NTDs having influential roles in proposing strategies to control and treat them around the world.

Aims: The present study aimed to assess the antibacterial effect of co-loaded rutin and curcumin in mesoporous silica nanoparticles (Cur-Rut-MSNs).

Background: Rutin is a nontoxic phytochemical that is present expansively in vegetables and fruits. Curcumin is an active ingredient of Curcuma longa. Curcumin and rutin have a variety of therapeutic effects, essentially antimicrobial, anti-inflammatory, and antioxidant actions.

Objective: Low aqueous solubility and poor bioavailability of rutin and curcumin limit their application in therapeutic goals. One of the advantageous routes to improve their bioavailability and solubility is nanoformulation. Co-delivery of therapeutic agents has been reported to have better therapeutic effects than monotherapy.

Methods: The present study has evaluated the antibacterial properties of Cur-Rut-MSNs. The Minimum Inhibitory Concentration (MIC) of Cur-Rut-MSNs has been assessed against different bacteria.

Results: Cur-Rut-MSNs exerted significantly higher antibacterial effect than curcumin-loaded MSNs (Cur-MSNs) and rutin-loaded MSNs (Rut-MSNs) against Acinetobacter baumannii, Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis (p<0.05).

Conclusion: The antibacterial effect was enhanced by the co-loading of rutin and curcumin in MSNs. According to the findings of this study, Cur-Rut-MSNs exhibit an antibacterial effect and can be a favorable nanoformulation against planktonic bacteria.

Background: A biofilm refers to a community of microbial cells that adhere to surfaces that are surrounded by an extracellular polymeric substance. Bacteria employ various defence mechanisms, including biofilm formation, to enhance their survival and resistance against antibiotics.

Objective: The current study aims to investigate the resistance patterns of Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis) in both biofilms and their planktonic forms.

Methods: E. coli and B. subtilis were used to compare resistance patterns in biofilms versus planktonic forms of bacteria. An antibiotic disc diffusion test was performed to check the resistance pattern of biofilm and planktonic bacteria against different antibiotics such as penicillin G, streptomycin, and ampicillin. Biofilm formation and its validation were done by using quantitative (microtiter plate assay) and qualitative analysis (Congo red agar media).

Results: A study of surface-association curves of E. coli and B. subtilis revealed that surface adhesion in biofilms was continuously constant as compared to their planktonic forms, thereby confirming the increased survival of bacteria in biofilms. Also, biofilms have shown high resistance towards the penicillin G, ampicillin and streptomycin as compared to their planktonic form.

Conclusion: It is safely inferred that E. coli and B. subtilis, in their biofilms, become increasingly resistant to penicillin G, ampicillin and streptomycin.

Background: Shiga Toxin-Producing Escherichia coli (E. coli) O157:H7, capable of causing serious food-borne illnesses, is extensively studied and is known to be transmitted through animal reservoirs or person-to-person contact, leading to severe disease outbreaks. The emergence of antibiotic resistance in these strains, coupled with increased adverse effects of existing therapeutics, underscores the urgent need for alternative therapeutic strategies.

Objective: This study aims to evaluate Glutamate Racemase (MurI protein) of the food-pathogenic E. coli O157:H7 (EC MurI) as a novel drug target. Furthermore, the study seeks to identify new compounds with potential inhibitory effects against this protein.

Methods: Using computational tools, the study identified inhibitor binding sites on EC MurI and identified relevant inhibitors capable of binding to these sites. Molecular docking techniques were employed to assess potential hits, and selected compounds were further analyzed for their structural activity and binding affinity to the protein.

Results: The results of the study revealed that Frigocyclinone and Deslanoside, exhibited the best binding affinity with EC-MurI. Subsequent molecular dynamic (MD) simulations of the selected complexes indicated that both compounds were stable. This suggests that Frigocyclinone and Deslanoside have the potential to serve as potent inhibitors of EC-MurI.

Conclusion: In summary, this study highlights the urgent need for alternative therapies against food-pathogenic E. coli, focusing on E. coli O157:H7. Evaluation of Glutamate Racemase as a drug target identified Frigocyclinone and Deslanoside as promising inhibitors. MD simulations indicated their stability, suggesting their potential as lead molecules for further research and treatment development.

Background: Iran has a relatively high prevalence of H. pylori, which correlates with high-risk areas for gastric cancer worldwide.

Methods: Our study aimed to investigate the underlying genetic mechanisms associated with resistance to metronidazole (frxA, rdxA), clarithromycin (23S rRNA), tetracycline (16S rRNA), and fluoroquinolone (gyrA) in H. pylori-positive dyspeptic patients using PCR and sequencing. We further examined the potential correlation between resistance profiles and various virulence genotypes.

Results: The rates of genetic mutations associated with resistance to metronidazole, fluoroquinolone, clarithromycin, and tetracycline were found to be 68%, 32.1%, 28.4%, and 11.1%, respectively. Well-documented multiple antibiotic resistance mutations were detected, such as rdxA and frxA (with missense and frameshift alterations), gyrA (Asp91, Asn87), 23S rRNA (A2142G, A2143G), and 16S rRNA (triple-base-pair substitutions AGA926-928→TTC). The cagA+ and vacA s1/m1 types were the predominant genotypes in our study. With the exception of metronidazole and tetracycline, no significant correlation was observed between the cagA+ and cagL+ genotypes and resistance-associated mutations.

Conclusion: The prevalence of antibiotic resistance-associated mutations in H. pylori was remarkably high in this region, particularly to metronidazole, ciprofloxacin, and clarithromycin. By conducting a simultaneous screening of virulence and resistance genotypes, clinicians can make informed decisions regarding the appropriate therapeutic regimen to prevent the escalation of antibiotic resistance against H. pylori infection in this specific geographical location.

Background: In this paper, we have discussed recent advances in our understanding of the aetiology of psoriasis, particularly as they relate to aryl hydrocarbon receptors in DCs, Langerhans cells, macrophages, signal transducer and activator of transcription 3 pathways, and dermal vascular endothelial cells. Here, we have shown that the ability to target specific cellular and molecular components of psoriasis pathogenesis with nanoscale precision using phosphodiesterase 4 inhibitors represents a transformative opportunity to address the complex nature of this dermatological condition.

Objective: In this review, we have examined the molecular mechanisms behind the pathogenic features of psoriasis and new treatments being tested in clinical settings. There is research being done on new treatments created in the last ten years. This field highlights the advantages of nanotechnological technologies as cutting-edge candidates for drug delivery systems in psoriasis and other inflammatory chronic skin disorders. Future Developments: Nanotechnology-based treatments currently under study show good efficacy and low side effect profiles. However, long-term prospective trials are required to demonstrate long-term safety and effectiveness. Phosphodiesterase inhibitors, Janus kinase inhibitors, nonsteroidal anti-inflammatory drugs, combinations of vitamin D3 derivatives and corticosteroids, and coal tar formulations are some of the newer topical treatments for psoriasis.

Conclusion: The psoriasis treatment continues to involve conventional medications (i.e., medicines that are generally acknowledged as either normal therapy or outdated remedies), whether used topically or orally. Nonetheless, we are starting to see initiatives to create pharmaceuticals and biosimilars with better therapeutic results, fewer side effects, and greater efficacy.