Precision Clinical Medicine最新文献

Owing to its constant exposure to the external environment and various stimuli, skin ranks among the organs most vulnerable to manifestations of aging. Preventing and delaying skin aging has become one of the prominent research subjects in recent years. Mesenchymal stem cells (MSCs) are multipotent stem cells derived from mesoderm with high self-renewal ability and multilineage differentiation potential. MSC-derived extracellular vesicles (MSC-EVs) are nanoscale biological vesicles that facilitate intercellular communication and regulate biological behavior. Recent studies have shown that MSC-EVs have potential applications in anti-aging therapy due to their anti-inflammatory, anti-oxidative stress, and wound healing promoting abilities. This review presents the latest progress of MSC-EVs in delaying skin aging. It mainly includes the MSC-EVs promoting the proliferation and migration of keratinocytes and fibroblasts, reducing the expression of matrix metalloproteinases, resisting oxidative stress, and regulating inflammation. We then briefly discuss the recently discovered treatment methods of MSC-EVs in the field of skin anti-aging. Moreover, the advantages and limitations of EV-based treatments are also presented.

Inflammatory bowel diseases (IBD) are a group of chronic relapsing gastrointestinal inflammatory diseases with significant global incidence. Although the pathomechanism of IBD has been extensively investigated, several aspects of its pathogenesis remain unclear. Long non-coding RNAs (lncRNAs) are transcripts with more than 200 nucleotides in length that have potential protein-coding functions. LncRNAs play important roles in biological processes such as epigenetic modification, transcriptional regulation and post-transcriptional regulation. In this review, we summarize recent advances in research on IBD-related lncRNAs from the perspective of the overall intestinal microenvironment, as well as their potential roles as immune regulators, diagnostic biomarkers and therapeutic targets or agents for IBD.

Background: Numerous investigations have revealed the interplay between gut microbiota (GM) and psoriasis (Ps) and psoriatic arthritis (PsA). However, the causal relationship between them remains unknown.

Methods: We curated a collection of genetic variants (P < 1 × 10^-5) associated with GM (n = 18 340) derived from the MiBioGen study. To explore the intricate relationship between GM and Ps as well as PsA, we harnessed the comprehensive resources of the FinnGen database, encompassing a vast cohort of individuals, including 4510 Ps cases and 212 242 controls and 1637 PsA cases and 212 242 controls. Mendelian randomization (MR) was used, including an inverse variance weighting method, followed by a sensitivity analysis to verify the robustness of the results.

Results: For Ps, some bacterial taxa, including Lactococcus, Ruminiclostridium 5, and Eubacterium fissicatena, were identified as risk factors; but Odoribacter demonstrated a protective effect against Ps. In the case of PsA, Lactococcus, Verrucomicrobiales, Akkermansia, Coprococcus 1, and Verrucomicrobiaceae were identified as risk factors; Odoribacter and Rikenellaceae exhibited a protective effect against the development of PsA.

Conclusion: Our study establishes a causal link between the GM and Ps and PsA. These findings provide insights into the underlying mechanisms and suggest potential therapeutic targets.

Background: Current knowledge on apolipoprotein A1 (APOA1) in hepatocellular carcinoma (HCC) is fragmented and even contradictory. Multi-dimensional analyses are required to comprehensively elucidate its value and underlying mechanism.

Methods: We collected 49 RNA-seq datasets, 40 cell line types data and 70 scRNA pan-cancer datasets public available, including 17 HCC datasets (1754 tumor samples), and enrolled 73 pairs of HCC tissue and 516 blood samples independently from our clinics. APOA1 impacting on the HCC tumor microenvironment (TME) was analyzed using intensive data mining. Methylation sequencing, flow cytometry, quantitative PCR, western blot, immunohistochemistry and clinical chemistry assays were conducted for wet experimental investigation.

Results: The APOA1 ontology fingerprint indicated that it played various crucial biological roles in HCC, primarily involved in cholesterol efflux. Consistent findings at histology, serology, and clinical follow-up revealed that high APOA1 was a good prognosis indicator of HCC. Hypermethylation in the APOA1 promoter region was found in clinical samples which is in accordance with the reduction of APOA1 in HCC. The cell cycle, DNA replication, mismatch repair pathways, and tumor cell proliferation were less observed in the HCC APOA1^high subgroup. The favorable immunoregulatory abilities of APOA1 showed interesting findings: a positive correlation between APOA1 and anti-tumor immune cells (NK, CD8⁺ T cells) and a negative association with immune cells exerting immunosuppressive effects, including M2 macrophages.

Conclusion: This is an integrative multidimensional exploration of APOA1 using bioinformatics and experiments. Both the prognostic value and anti-tumor effects based on APOA1 panoramic exploration in the HCC TME demonstrate a new potential clinical target for HCC assessment and intervention in the future.