New sights of low dose IL-2: Restoration of immune homeostasis for viral infection.

Viral infection poses a significant threat to human health. In addition to the damage caused by viral replication, the immune response it triggers often leads to more serious adverse consequences. After the occurrence of viral infection, in addition to the adverse consequences of infection, chronic infections can also lead to virus-related autoimmune diseases and tumours. At the same time, the immune response triggered by viral infection is complex, and dysregulated immune response may lead to the occurrence of immune pathology and macrophage activation syndrome. In addition, it may cause secondary immune suppression, especially in patients with compromised immune system, which could lead to the occurrence of secondary infections by other pathogens. This can often result in more severe clinical outcomes. Therefore, regarding the treatment of viral infections, restoring the balance of the immune system is crucial in addition to specific antiviral medications. In recent years, scientists have made an interesting finding that low dose IL-2 (ld-IL-2) could potentially have a crucial function in regulating the immune system and reducing the chances of infection, especially viral infection. Ld-IL-2 exerts immune regulatory effects in different types of viral infections by modulating CD4+ T subsets, CD8+ T cells, natural killer cells, and so on. Our review summarised the role of IL-2 or IL-2 complexes in viral infections. Ld-IL-2 may be an effective strategy for enhancing host antiviral immunity and preventing infection from becoming chronic; additionally, the appropriate use of it can help prevent excessive inflammatory response after infection. In the long term, it may reduce the occurrence of infection-related autoimmune diseases and tumours by promoting the restoration of early immune homeostasis. Furthermore, we have also summarised the application of ld-IL-2 in the context of autoimmune diseases combined with viral infections; it may be a safe and effective strategy for restoring immune homeostasis without compromising the antiviral immune response. In conclusion, focusing on the role of ld-IL-2 in viral infections may provide a new perspective for regulating immune responses following viral infections and improving prognosis.

Identification of novel carbonic anhydrase II receptor-targeting drugs for treating myocardial infarction through the mechanism of Xue-Fu-Zhu-Yu decoction.

Myocardial infarction (MI) is a significant threat to human health and life. Xue-Fu-Zhu-Yu Decoction (XFZYD), a renowned traditional Chinese medicine prescription for treating myocardial infarction, is known to play a significant role in the management of MI. However, its mechanism of action remains unclear. Through network pharmacology analysis of compound-target interactions, we have identified Carbonic Anhydrase II (CA2) as a critical target for XFZYD in the treatment of MI. Subsequently, we will embark on a target-based drug design approach with a focus on CA2 as the key target: Pharmacophore modeling: Two pharmacophore models were developed and validated to screen for small molecules with CA2 inhibitory features. Virtual screening: Based on two pharmacophore models, small molecules with the property of binding to the CA2 target were screened from a virtual screening library. Molecular docking: Molecular docking was employed to identify small molecules with stable binding affinity to CA2. ADMET prediction: ADMET models were utilized to screen for small molecules with favorable pharmacological properties. Molecular dynamics: Molecular dynamics simulations were further conducted to analyze the binding modes of the selected small molecules with CA2, ultimately resulting in the identification of Ligand 3 and Ligand 5 as small molecule inhibitors targeting CA2. Finally, the mechanisms underlying the anti-MI effects were discussed. The primary objective of this article is to uncover the mechanism by which XFZYD acts on MI and utilize it for drug development. These findings provide novel avenues for the development of anti-MI drugs.Communicated by Ramaswamy H. Sarma.

Establishment of a novel nomogram for the clinically diagnostic prediction of minimal change disease, -a common cause of nephrotic syndrome.

BACKGROUND: Minimal change disease (MCD) is one of the major causes of nephrotic syndrome (NS). A confirmed MCD diagnosis mainly depends on renal biopsy at present, which is an invasive procedure with many potential risks. The overall incidence of complications caused by renal biopsy procedures has been reported as approximately 11 and 6.6% outside and within China, respectively. Unfortunately, there is currently no noninvasive procedure or practical classification method for distinguishing MCD from other primary glomerular diseases available. METHOD: A total of 1009 adult patients who underwent renal biopsy between January 2017 and November 2019 were enrolled in this study. Twenty-five parameters extracted from patient demographics, clinical manifestations, and laboratory test results were statistically analysed. LASSO regression analysis was further performed on these parameters. The parameters with the highest area under the curve (AUC) were selected and used to establish a logistic diagnostic prediction model. RESULTS: Of the 25 parameters, 14 parameters were significantly different (P < 0.05). MCD patients were mostly younger (36 (22, 55) vs. 41 (28.75, 53)) and male (59% vs. 52%) and had lower levels of diastolic blood pressure (DBP) (79 (71, 85.5) vs. 80 (74, 89)) and IgG (5.42 (3.17, 6.36) vs. 9.38 (6.79, 12.02)) and higher levels of IgM (1.44 (0.96, 1.88) vs. 1.03 (0.71, 1.45)) and IgE (160 (46.7, 982) vs. 47.3 (19, 126)) than those in the non-MCD group. Using the LASSO model, we established a classifier for adults based on four parameters: DBP and the serum levels of IgG, IgM, IgE. We were able to clinically classify adult patients with NS into MCD and non-MCD using this model. The validation accuracy of the logistic regression model was 0.88. A nomogram based on these four classifiers was developed for clinical use that could predict the probability of MCD in adult patients with NS. CONCLUSIONS: A LASSO model can be used to distinguish MCD from other primary glomerular diseases in adult patients with NS. Combining the model and the nomogram potentially provides a novel and valuable approach for nephrologists to diagnose MCD, avoiding the complications caused by renal biopsy.

Glutaraldehyde-polymerized hemoglobin and tempol (PolyHb-tempol) has superoxide dismutase activity that can attenuate oxidative stress on endothelial cells induced by superoxide anion.

A Tempol compound with an amine group (4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl, NH2-Tempol) was cross-linked to hemoglobin in a one-step polymerization reaction to produce a novel hemoglobin-based oxygen carrier (HBOC) designated PolyHb-Tempol. The reaction parameters, including the reaction time, pH, temperature, and ratio of reactants, were optimized, and the physiochemical properties of the resulting product were characterized. PolyHb-Tempol didn't show any toxicity towards endothelial cells. Furthermore, from observations of cell morphology and viability, PolyHb-Tempol showed a significant ability to inhibit or eliminate oxidative stress induced by superoxide free radicals. These results suggest that PolyHb-Tempol may potentially be suitable as an HBOC.