Yi-Bing Wang

Lung adenocarcinoma (LUAD) poses a significant global health burden owing to its high incidence rate and unfavorable prognosis, driven by frequent recurrence and drug resistance. Understanding the biological mechanisms underlying LUAD is imperative to developing advanced therapeutic strategies. Recent research has highlighted the role of dysregulated microRNAs (miRNAs) in LUAD progression through diverse signaling pathways, including the Wnt and AKT pathways. Of particular interest is the novel pathological mechanism involving the interaction between competing endogenous RNAs (ceRNAs) and miRNAs. This review critically analyzed the impact of aberrant miRNA expression on LUAD development, shedding light on the associated signaling pathways. It also highlighted the emerging significance of ceRNA‑miRNA interactions in LUAD pathogenesis. Elucidating the intricate regulatory networks involving miRNAs and ceRNAs presents a promising avenue for the development of potential therapeutic interventions and diagnostic biomarkers in LUAD. Further research in this area is essential to advance precision medicine approaches and improve patient outcomes.

Background: With fast rising incidence, papillary thyroid carcinoma (PTC) is the most common head and neck cancer. Parthenolide, isolated from traditional Chinese medicine, inhibits various cancer cells, including PTC cells. The aim was to investigate the lipid profile and lipid changes of PTC cells when treated with parthenolide. Methods: Comprehensive lipidomic analysis of parthenolide treated PTC cells was conducted using a UHPLC/Q-TOF–MS platform, and the changed lipid profile and specific altered lipid species were explored. Network pharmacology and molecular docking were performed to show the associations among parthenolide, changed lipid species, and potential target genes. Results: With high stability and reproducibility, a total of 34 lipid classes and 1736 lipid species were identified. Lipid class analysis indicated that parthenolide treated PTC cells contained higher levels of fatty acid (FA), cholesterol ester (ChE), simple glc series 3 (CerG3) and lysophosphatidylglycerol (LPG), lower levels of zymosterol (ZyE) and Monogalactosyldiacylglycerol (MGDG) than controlled ones, but with no significant differences. Several specific lipid species were changed significantly in PTC cells treated by parthenolide, including the increasing of phosphatidylcholine (PC) (12:0e/16:0), PC (18:0/20:4), CerG3 (d18:1/24:1), lysophosphatidylethanolamine (LPE) (18:0), phosphatidylinositol (PI) (19:0/20:4), lysophosphatidylcholine (LPC) (28:0), ChE (22:6), and the decreasing of phosphatidylethanolamine (PE) (16:1/17:0), PC (34:1) and PC (16:0p/18:0). Four key targets (PLA2G4A, LCAT, LRAT, and PLA2G2A) were discovered when combining network pharmacology and lipidomics. Among them, PLA2G2A and PLA2G4A were able to bind with parthenolide confirmed by molecular docking. Conclusions: The changed lipid profile and several significantly altered lipid species of parthenolide treated PTC cells were observed. These altered lipid species, such as PC (34:1), and PC (16:0p/18:0), may be involved in the antitumor mechanisms of parthenolide. PLA2G2A and PLA2G4A may play key roles when parthenolide treated PTC cells.

Background: Inflammation and immune dysfunction play significant roles in the pathogenesis of Alzheimer's disease (AD)-related dementia. Changes in peripheral blood cell profiles are a common manifestation of inflammation and immune dysfunction and have been reported in patients with AD or mild cognitive impairment (MCI). We systematically evaluated the association of peripheral blood cell counts and indices with AD or MCI through a meta-analysis.Methods: We electronically searched sources to identify all case–control trials comparing peripheral blood cell counts and/or lymphocyte subsets between patients with AD or MCI and healthy controls (HCs). Meta-analyses were used to estimate the between-group standardized mean difference (SMD) and 95% confidence interval (CI).Results: A total of 36 studies involving 2,339 AD patients, 608 MCI patients, and 8,352 HCs were included. AD patients had significantly decreased lymphocyte counts (SMD −0.345, 95% CI [−0.545, −0.146], P = 0.001) and significantly increased leukocyte counts (0.140 [0.039, 0.241], P = 0.006), neutrophil counts (0.309 [0.185, 0.434], P = 0.01), and neutrophil–lymphocyte ratio (NLR) (0.644 [0.310, 0.978], P < 0.001) compared to HCs. Similarly, significantly increased leukocyte counts (0.392 [0.206, 0.579], P < 0.001), NLR (0.579 [0.310, 0.847], P < 0.001), and neutrophil counts (0.248 [0.121, 0.376], P < 0.001) were found in MCI patients compared with HCs. A significantly decreased percentage of B lymphocytes (−1.511 [−2.775, −0.248], P = 0.019) and CD8⁺ T cells (−0.760 [−1.460, −0.061], P = 0.033) and a significantly increased CD4/CD8 ratio (0.615 [0.074, 1.156], P = 0.026) were observed in AD patients compared to HCs. Furthermore, significant changes in hemoglobin level and platelet distribution width were found in patients with AD or MCI compared with HCs. However, no significant difference was found between AD or MCI patients and HCs in terms of platelet counts, mean corpuscular volume, red cell distribution width, mean platelet volume, and CD4⁺ T, CD3⁺ T, or natural killer cell counts.Conclusion: Changes in peripheral blood cell profiles, particularly involving leukocyte, lymphocyte, neutrophil, and CD8⁺ T cell counts, as well as the NLR and the CD4/CD8 ratio, are closely associated with AD. The diagnostic relevance of these profiles should be investigated in future.

Background: Transfer RNA-derived fragments (tRFs) and transfer RNA halves (tiRNAs) have been shown to play crucial roles in gene regulation. This study aims to reveal the expression profiles of tRFs and tiRNAs and their possible biological roles in lung adenocarcinoma (LUAD). Methods: Five paired clinical lung adenocarcinoma tissues (LAT) and adjacent normal lung tissues (ANLT) were selected to analyze the expression of tRFs and tiRNAs. Six significantly expressed tRFs and tiRNAs were selected and validated by Quantitative Real-time PCR (qPCR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Results: The sequencing results showed that 109 tRFs and tiRNAs were differentially expressed between LAT and ANLT, out of which 60 were upregulated and 49 were downregulated. Compared with ANLT, lower expression levels of 3 tRF-1s (tRF-Ser-TGA-010, tRF-Arg-CCT-018, and tRF-Val-CAC-017) in LAT were verified by qPCR. Subsequently, the putative target genes of tRF-1s were analyzed by computational prediction and the top 10 significant results of GO and KEGG pathway enrichment analysis were presented. Conclusions: This study has revealed the landscape of tRF and tiRNA expression profiles in LUAD. Three newly found differentially expressed downregulated tRF-1s may be involved in the pathogenesis of LUAD and may serve as potential diagnostic biomarkers, or otherwise reconcile target genes for drug development.