Origami of KR-12 Designed Antimicrobial Peptides and Their Potential Applications.

This review describes the discovery, structure, activity, engineered constructs, and applications of KR-12, the smallest antibacterial peptide of human cathelicidin LL-37, the production of which can be induced under sunlight or by vitamin D. It is a moonlighting peptide that shows both antimicrobial and immune-regulatory effects. Compared to LL-37, KR-12 is extremely appealing due to its small size, lack of toxicity, and narrow-spectrum antimicrobial activity. Consequently, various KR-12 peptides have been engineered to tune peptide activity and stability via amino acid substitution, end capping, hybridization, conjugation, sidechain stapling, and backbone macrocyclization. We also mention recently discovered peptides KR-8 and RIK-10 that are shorter than KR-12. Nano-formulation provides an avenue to targeted delivery, controlled release, and increased bioavailability. In addition, KR-12 has been covalently immobilized on biomaterials/medical implants to prevent biofilm formation. These constructs with enhanced potency and stability are demonstrated to eradicate drug-resistant pathogens, disrupt preformed biofilms, neutralize endotoxins, and regulate host immune responses. Also highlighted are the safety and efficacy of these peptides in various topical and systemic animal models. Finaly, we summarize the achievements and discuss future developments of KR-12 peptides as cosmetic preservatives, novel antibiotics, anti-inflammatory peptides, and microbiota-restoring agents.

Antibiotic Prophylaxis for Orthopaedic Implant Removal: What Does the Evidence Say?

Orthopaedic implant removal is considered a sterile procedure, but the current literature suggests it is associated with around a 20% Surgical Site Infection (SSI) rate. The use of antibiotic prophylaxis is still ambiguous and contentious. Taking into consideration this issue we conducted a meta-analysis for the use of antibiotic prophylaxis in orthopaedic implant removal surgery. OBJECTIVES: To determine whether or not antibiotic prophylaxis benefits orthopaedic implant removal surgeries. METHODS: Electronic and printed sources were searched up to February 2021 for randomised controlled trials (RCTs) using antibiotic prophylaxis and a control group. Data from eligible studies were pooled for the following outcomes: overall, superficial, and deep surgical site infection (SSI). Pooled odds ratios with a 95% confidence interval (CI) were calculated using Mantel Haenszel fixed-effect model preferentially. RESULTS: Two studies, including 766 patients were included in this meta-analysis. Heterogeneity was not statistically significant between the studies. There was no significant difference in the incidence of overall SSI in cefazolin and normal saline (NS) groups (Pooled OR 0.79; 95% CI 0.53- 1.17). In subgroup analysis, antibiotic prophylaxis showed statistically significant improvement for deep SSI (Pooled OR 0.20; 95% CI 0.06-0.70). CONCLUSION: Overall incidence of SSI is not reduced after the administration of antibiotic prophylaxis one hour before removal of orthopaedic implants.

Exploration of potential role of Rho GTPase in nicotine dependence-induced withdrawal syndrome in mice.

The RhoA gene showed an important genotypic association with nicotine dependence and smoking initiation. The current study aims to investigate the effect of the Rho GTPase inhibitor ML141 in the progression of nicotine dependence in a mice model of precipitated nicotine withdrawal syndrome by mecamylamine.The experimental procedure involved administration of 2.5 mg/kg nicotine dissolved in normal saline subcutaneously (s.c) four times a day consecutively for 7 days and last single dose in the morning on 8th day. ML-141 was dissolved in dimethyl sulfoxide (DMSO) and was administered daily with nicotine as corrective treatment at a dose of 1,5 and 10 mg/kg (p < 0.05). An injection of 3 mg/kg of mecamylamine intraperitoneal (ip) was given an hour later than the last nicotine dose on the day 8 to precipitate withdrawal of nicotine and withdrawal severity was assessed by measuring hyperalgesia, piloerection, jumping frequency, tremors, and withdrawal severity score (WSS). Various behavioural changes such as hyperalgesia, piloerection, jumping frequency, and tremors were monitored and WSS was calculated. ML-141 a selective Rho GTPase inhibitor was found to show dose-dependent effect on all these parameters. Inhibition of Rho GTPase was found to reduce the severity of withdrawal syndrome; therefore, it can be concluded that Rho GTPase would serve as a suitable biological target by regulating the reward system in brain and could be used as new target for drug discovery.