A review on the epidemiology of invasive fungal infections in Asian patients with haematological malignancies (2011-2021).

The incidences of invasive fungal infection (IFI) are increasing especially in patients diagnosed with haematological malignancies due to their immunocompromised nature. Risk factors include advanced age, exposure to immunosuppressants, neutropenia and catheter usage. Some of the most common organisms reported are Candida and Aspergillus species while other fungal species including Scedosporium, Ttrichosporon, Cryptococcus and Fusarium have also increasingly been reported in the past years. However, the epidemiological data on IFI amongst patients with haematological malignancies in Asian countries are lacking and therefore, we aim to investigate published epidemiological data on such cases in the last 10 years (2011-2021) and to discuss the challenges faced in the diagnosis and management of IFI.

Discovery of lung adenocarcinoma tumor antigens and ferroptosis subtypes for developing mRNA vaccines.

mRNA vaccines are becoming a feasible alternative for treating cancer. To develop mRNA vaccines against LUAD, potential antigens were identified and LUAD ferroptosis subtypes distinguished for selecting appropriate patients. The genome expression omnibus, cancer genome atlas (TCGA) and FerrDB were used to collect gene expression profiles, clinical information, and the genes involved in ferroptosis, respectively. cBioPortal was used to visualize and compare genetic alterations, GEPIA2 to calculate prognostic factors of the selected antigens, and TIMER to visualize the relationship between potential antigens and tumor immune cell infiltration. Consensus clustering analysis was utilized to identify ferroptosis subtypes and their prognostic value assessed by Log-rank and cox regression tests. The modules of ferroptosis-related gene screening were conducted by weight gene co-expression network analysis. The LUAD ferroptosis landscape was visualized through dimensionality reduction and graph learning. Six tumor antigens had obvious LUAD-mutations, positively correlated with different antigen-presenting cells, and might induce tumor cell ferroptosis. LUAD patients were stratified into three ferroptosis subtypes (FS1, FS2, and FS3) according to diverse molecular, cellular, and clinical characteristics. FS3 showed the highest tumor mutation burden and the most somatic mutations, deemed potential indicators of mRNA vaccine effectiveness. Moreover, different ferroptosis subtypes expressed distinct immune checkpoints and immunogenic cell death modulators. AGPS, NRAS, MTDH, PANX1, NOX4, and PPARD are potentially suitable for mRNA vaccinations against LUAD, specifically in patients with FS3 tumors. This study defines vaccination candidates and establishes a theoretical basis for LUAD mRNA vaccinations.

Down-regulation of miR-21-5p by pirfenidone to inhibit fibroblast proliferation in the treatment of acquired tracheal stenosis.

OBJECTIVE: Treatment options for acquired tracheal stenosis (ATS) are limited due to a series of pathophysiological changes including inflammation and cell proliferation. Micro ribonucleic acid-21-5p (miR-21-5p) may promote the excessive proliferation of fibroblasts. However, various types of fibrosis can be prevented with pirfenidone (PFD). Currently, the effect of PFD on miR-21-5p and its biological function has not been clarified. In this study, PFD was evaluated as a potential treatment for ATS by inducing fibroblast proliferation in lipopolysaccharide (LPS)-induced fibroblasts by targeting miR-21-5p. METHODS: For 48 h, 1 g/ml LPS was used to generate fibroblasts in vitro, followed by the separation of cells into four groups: control, PFD, mimic, and mimic + PFD. The Cell Counting Kit-8 (CCK-8) technique was adopted to measure the proliferation of fibroblasts. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB) were used to measure the relative expressions of tumor necrosis factor-α (TNF-α), transforming growth factor-ß1 (TGF-ß1), drosophila mothers against decapentaplegic 7 (Smad7) and collagen type I alpha 1(COL1A1) messenger RNA (mRNA) and proteins, respectively. RESULTS: (1) At 0, 24, 48, and 72 h, fibroblast growth was assessed using the CCK-8 method. Compared with the control group, the mimic group showed the highest fibroblast viability, and the PFD group showed the lowest fibroblast viability. However, fibroblast viability increased in the mimic + PFD group but decreased in the mimic one. (2) RT-qPCR and WB showed that the mimic group exhibited a significant up-regulation in the relative expressions of TNF-α, TGF-ß1, and COL1A1 mRNA and proteins but a down-regulation in the relative expression of Smad7 mRNA and protein compared with the control one. In the PFD group, the results were the opposite. Nevertheless, the relative expressions of TNF-α, TGF-ß1, and COL1A1 mRNA and proteins were increased, whereas that of Smad7 mRNA was decreased in the mimic + PFD group. The change was less in the mimic group. CONCLUSION: PFD may have a preventive and curative effect on ATS by inhibiting fibroblast proliferation and the fibrotic process and possibly through down-regulating miR-21-5p and up-regulating Smad7 and its mediated fibrotic and inflammatory responses.