Personalized decision support system for tailoring IgA nephropathy treatment strategies.

BACKGROUND: The ongoing debate surrounding the use of immunosuppressive treatments for IgA nephropathy (IgAN) underscores the demand for personalized and effective strategies. METHODS: Analyzed data from 807 IgAN patients over 5+ years using three methods: Random Forest with molecular biomarkers, network biomarkers with graph engineering, and an auto-encoder model. All models were trained using identical demographic, clinical, and pathological data, employing an 80-20 split for training and testing purposes. RESULTS: In the comprehensive assessment of IgAN prognosis, the Random Forest model, employing molecular biomarkers, demonstrated strong performance metrics (AUC = 0.83, sensitivity = 0.51, specificity = 0.96). However, traditional graph feature engineering on patient-specific networks outperformed these results with an AUC of 0.90, sensitivity of 0.64, and specificity of 0.94. The Auto-encoder model showed the best accuracy (AUC = 0.91, sensitivity = 0.46, specificity = 0.96). The findings highlighted the superior predictive capabilities of network biomarkers over molecular biomarkers for adverse renal outcome prediction in IgAN. Consequently, we integrated Auto-encoder-derived Network Biomarkers with Random Forest Models to enhance prognostic precision in diverse IgAN treatment scenarios. The prediction for the prognosis of patients receiving supportive care, glucocorticoid therapy, and immunosuppressant treatment yielded AUC values of 0.95, 0.96, and 1, respectively, indicating high specificity. Drawing from these insights, we pioneered the development of an innovative decision support model for IgAN treatment. This model demonstrated the ability to make medical decisions comparable to those by experienced nephrologists, enabling the customization of personalized disease management strategies. CONCLUSION: Our system accurately predicted IgAN prognosis and evaluated various treatment efficacies, aiding physicians in devising optimal therapeutic strategies for patients.

Preclinical Pharmacokinetics, Biodistribution, and Acute Toxicity Evaluation of Caerin 1.9 Peptide in Sprague Dawley Rats.

Caerin 1.9 is a natural peptide derived from the skin secretions of the Australian tree frog (Litoria) with broad-spectrum antimicrobial and anticancer bioactivity. It improves the efficacy of a therapeutic vaccine and immune checkpoint inhibitor therapy when injected intratumorally and inhibits TC-1 tumor growth when applied topically through intact skin in a TC-1 murine tumor model. This paper investigated the pharmaceutical kinetic profile, the tissue distribution, and the acute safety investigation of Caerin 1.9 peptide in Sprague Dawley (SD) rats. The results showed that subcutaneous injection of Caerin 1.9 at 100 mg/kg is safe and does not cause mortality or organ malfunction in the recipient rats. For the consecutive injection of F3 at 10 mg/kg, the peak concentration (C max) of F3 displayed at 1 hr after injection in male rats was 591 ng/mL, the average drug retention time was 0.807 hr, T 1/2 was 4.58 hr, and AUC0-last was 1890 h × ng/mL. In female rats, C max was 256 ng/mL, with an average drug retention time of 2.96 hr, T 1/2 of 1.33 hr, and AUC0-last of 740 h × ng/mL. The results showed that the concentration of Caerin 1.9 in the peripheral blood peaked at 1 hour. As injected concentration increased, T 1/2 extended, and C max, AUC0-last, and volume of distribution at a steady state all increased. After 14 days of repeated subcutaneous injection at 10.0 mg/kg, no accumulation of Caerin 1.9 in plasma was observed. The results of tissue distribution showed that the Caerin 1.9 is below the LC-MS/MS detection threshold at a minimum concentration of 40 ng/g. In conclusion, Caerin 1.9 is well tolerated in rats and could be used with current immunotherapies for better management of solid tumors and genital warts.

Caerin 1 Peptides, the Potential Jack-of-All-Trades for the Multiple Antibiotic-Resistant Bacterial Infection Treatment and Cancer Immunotherapy.

Antibiotic resistance-related bacterial infections and cancers become huge challenges in human health in the 21st century. A number of naturally derived antimicrobial peptides possess multiple functions in host defense, including anti-infective and anticancer activities. One of which is known as the caerin 1 family peptides. The microbicidal properties of these peptides have been long discussed. The recent studies also established the usage of two members in this family, caerin 1.1 and caerin 1.9, in antimultiple antibiotic-resistant bacteria species. It is increasingly evident that caerin 1.1 and caerin 1.9 also contain additional activities in the suppression of tumor. In this review, we briefly outline the therapeutic potentials and possible mechanism of action of caerin 1.1 and 1.9 in the treatment of multiple antibiotic-resistant bacterial infection and cancer immunotherapy.

Caerin 1.1 and 1.9 Peptides from Australian Tree Frog Inhibit Antibiotic-Resistant Bacteria Growth in a Murine Skin Infection Model.

The host defense peptide caerin 1.9 was originally isolated from skin secretions of an Australian tree frog and inhibits the growth of a wide range of bacteria in vitro. In this study, we demonstrated that caerin 1.9 shows high bioactivity against several bacteria strains, such as Staphylococcus aureus, Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), and Streptococcus haemolyticus in vitro. Importantly, unlike the antibiotic Tazocin, caerin 1.9 does not induce bacterial resistance after 30 rounds of in vitro culture. Moreover, caerin 1.1, another peptide of the caerin family, has an additive antibacterial effect when used together with caerin 1.9. Furthermore, caerin 1.1 and 1.9 prepared in the form of a temperature-sensitive gel inhibit MRSA growth in a skin bacterial infection model of two murine strains. These results indicate that caerin 1.1 and 1.9 peptides could be considered an alternative for conventional antibiotics. IMPORTANCE Antibiotic-resistant bacteria cause severe problems in the clinic. We show in our paper that two short peptides isolated from an Australian frog and prepared in the form of a gel are able to inhibit the growth of antibiotic-resistant bacteria in mice, and, unlike antibiotics, these peptides do not lead to the development of peptide-resistant bacteria strains.