Computational Prediction of Protein-Protein Interactions of Human Tyrosinase

The various studies on tyrosinase have recently gained the attention of researchers due to their potential application values and the biological functions. In this study, we predicted the 3D structure of human tyrosinase and simulated the protein-protein interactions between tyrosinase and three binding partners, four and half LIM domains 2 (FHL2), cytochrome b-245 alpha polypeptide (CYBA), and RNA-binding motif protein 9 (RBM9). Our interaction simulations showed significant binding energy scores of −595.3 kcal/mol for FHL2, −859.1 kcal/mol for CYBA, and −821.3 kcal/mol for RBM9. We also investigated the residues of each protein facing toward the predicted site of interaction with tyrosinase. Our computational predictions will be useful for elucidating the protein-protein interactions of tyrosinase and studying its binding mechanisms

Construction and Application of Standardized Postoperative Pain-Management Procedure for Patients With Perianal Abscess: A Retrospective Study

ObjectiveThe present study explored the construction and application of a standardized postoperative pain-management procedure for patients with perianal abscess.MethodsTwo study groups (the observation group and the intervention group) were established retrospectively. The observation group comprised 46 patients with perianal abscess who enrolled in this study between June 2019 and June 2020. The intervention group comprised 48 patients who enrolled in the study between July 2020 and July 2021. All patients were enrolled using the convenience sampling method. A pain-management team was established, and standardized procedure management was implemented in the intervention group, while routine pain management was implemented in the observation group. Indices related to the patients' postoperative pain-control satisfaction and rehabilitation were compared between the two groups.ResultsThe patients' pain-control satisfaction, wound edema score, edema disappearance time, urinary retention, and defecation difficulty following intervention were better in the intervention group than in the observation group, and the differences were statistically significant (P < 0.05 for all).ConclusionThe implementation of the standardized postoperative pain-management procedure in patients with perianal abscess can effectively improve the patient's level of pain and satisfaction and promote rehabilitation

Towards Al3+-Induced Manganese-Containing Superoxide Dismutase Inactivation and Conformational Changes: An Integrating Study with Docking Simulations

Superoxide dismutase (SOD, EC 1.15.1.1) plays an important antioxidant defense role in skins exposed to oxygen. We studied the inhibitory effects of Al3+ on the activity and conformation of manganese-containing SOD (Mn-SOD). Mn-SOD was significantly inactivated by Al3+ in a dose-dependent manner. The kinetic studies showed that Al3+ inactivated Mn-SOD follows the first-order reaction. Al3+ increased the degree of secondary structure of Mn-SOD and also disrupted the tertiary structure of Mn-SOD, which directly resulted in enzyme inactivation. We further simulated the docking between Mn-SOD and Al3+ (binding energy for Dock 6.3: −14.07 kcal/mol) and suggested that ASP152 and GLU157 residues were predicted to interact with Al3+, which are not located in the Mn-contained active site. Our results provide insight into the inactivation of Mn-SOD during unfolding in the presence of Al3+ and allow us to describe a ligand binding via inhibition kinetics combined with the computational prediction

Preparation and Characterization of Baicalein-Loaded Nanoliposomes for Antitumor Therapy

Baicalein (BAI) is a major constituent of Scutellaria baicalensis Georgi. Previous studies showed that BAI had obvious effects on U14 cervical tumor-bearing mice model and HeLa cells. However, the use of BAI is inconvenient and troublesome, due to its low oral bioavailability. The aim of this study was to develop baicalein-loaded nanoliposomes (BAI-LP) to improve its bioavailability. In this study, BAI-LP was prepared by thin film hydration method. The average size, polydispersity index (PDI), zeta potential and encapsulation efficiency (EE) of the BAI-LP were 194.6±2.08 nm, 0.17±0.025, -30.73±0.41 mV, and 44.3±2.98%, respectively. Drug storage stability study showed no significant changes in these values after 4 weeks of storing at 4°C. Additionally, Sulforhodamine B (SRB) experimental results indicated that the BAI-LP could achieve better anti-tumor effects than free BAI. The results of the experiment demonstrated that BAI-LP had a better antitumor effect with a higher inhibition rate of 66.34±15.33% than free BAI with a inhibition rate of 41.89±10.50% by using U14 cervical tumor-bearing mice model. In conclusion, the study suggested that BAI-LP would serve as a potent delivery vehicle for BAI in future cancer therapy

Antibiotic synergist OM19r reverses aminoglycoside resistance in multidrug-resistant Escherichia coli

Introduction: The continued emergence and spread of multidrug-resistant (MDR) bacterial pathogens require a new strategy to improve the efficacy of existing antibiotics. Proline-rich antimicrobial peptides (PrAMPs) could also be used as antibacterial synergists due to their unique mechanism of action. Methods: Utilizing a series of experiments on membrane permeability, In vitro protein synthesis, In vitro transcription and mRNA translation, to further elucidate the synergistic mechanism of OM19r combined with gentamicin. Results: A proline-rich antimicrobial peptide OM19r was identified in this study and its efficacy against Escherichia coli B2 (E. coli B2) was evaluated on multiple aspects. OM19r increased antibacterial activity of gentamicin against multidrug-resistance E. coli B2 by 64 folds, when used in combination with aminoglycoside antibiotics. Mechanistically, OM19r induced change of inner membrane permeability and inhibited translational elongation of protein synthesis by entering to E. coli B2 via intimal transporter SbmA. OM19r also facilitated the accumulation of intracellular reactive oxygen species (ROS). In animal models, OM19r significantly improved the efficacy of gentamicin against E. coli B2. Discussion: Our study reveals that OM19r combined with GEN had a strong synergistic inhibitory effect against multi-drug resistant E. coli B2. OM19r and GEN inhibited translation elongation and initiation, respectively, and ultimately affected the normal protein synthesis of bacteria. These findings provide a potential therapeutic option against multidrug-resistant E. coli