[Research progress on bioinformatics in pulmonary arterial hypertension]. / ç”Ÿç‰©ä¿¡æ¯å­¦åœ¨è‚ºåŠ¨è„‰é«˜åŽ‹ä¸­çš„ç ”ç©¶è¿›å±•.

Pulmonary arterial hypertension (PAH) is a severe disease characterized by abnormal pulmonary vascular remodeling and increased right ventricular pressure load, posing a significant threat to patient health. While some pathological mechanisms of PAH have been revealed, the deeper mechanisms of pathogenesis remain to be elucidated. In recent years, bioinformatics has provided a powerful tool for a deeper understanding of the complex mechanisms of PAH through the integration of techniques such as multi-omics analysis, artificial intelligence, and Mendelian randomization. This review focuses on the bioinformatics methods and technologies used in PAH research, summarizing their current applications in the study of disease mechanisms, diagnosis, and prognosis assessment. Additionally, it analyzes the existing challenges faced by bioinformatics and its potential applications in the clinical and basic research fields of PAH in the future.

The Overexpression of Fibronectin 1 Promotes Cancer Progression and Associated with M2 Macrophages Polarization in Head and Neck Squamous Cell Carcinoma Patients.

Purpose: This study aimed to investigate the biological roles of fibronectin 1 (FN1) in head and neck squamous cell carcinoma (HNSCC) and its effects on macrophage M2 polarization. Methods: We analyzed FN1 expression pattern and examined its clinical relevance in HNSCC progression by bioinformatic analysis. Small interfering RNA (siRNA) was utilized to silence FN1 in HNSCC cells. Cell counting kit-8 (CCK-8) assay, colony formation assay, Transwell assay and wound healing assay were performed to reveal the effect of FN1 on malignant behaviors of HNSCC cells. Moreover, a co-culture model of macrophages and HNSCC cells was established to investigate whether FN1 induce macrophage M2 polarization. Finally, we used bioinformatic methods to explore the possible FN1-related pathways in HNSCC. Results: FN1 is significantly overexpressed in HNSCC patients and has been obviously correlated with higher pathological stage and poor prognosis. Downregulation of FN1 suppressed the proliferation, migration and invasion of HNSCC cells, and inhibited macrophage M2 polarization in vitro. In addition, "PI3K-Akt" and "MAPK" signaling pathways may be involved in the malignant process of FN1 in HNSCC. Conclusion: The overexpression of FN1 promotes HNSCC progression and induces macrophages M2 polarization. FN1 may serve as a promising prognostic biomarker and therapeutic target in HNSCC.

Overexpression of DOCK6 in oral squamous cell cancer promotes cellular migration and invasion and is associated with poor prognosis.

OBJECTIVE: We aimed to identify the role of DOCK6 in oral squamous cell cancer (OSCC) in this study. DESIGN: DOCK6 expression in OSCC was analyzed using TCGA and GEO datasets and was verified by quantitative real-time PCR, Western blotting, and immunohistochemistry. Statistical analyses were performed to evaluate the relationships between DOCK6 expression and the clinicopathological characteristics of OSCC patients. Wound healing and Transwell assays were performed to assess OSCC cell migration and invasion, respectively. STRING and GO analyses and gene set enrichment analysis were used to identify DOCK6-interacting proteins, their functions and their potential pathways. RESULTS: DOCK6 was significantly upregulated at both the mRNA and protein levels in OSCC tissues (all P < 0.05). DOCK6 levels were positively correlated with age (P < 0.05), lymph node metastasis status (P < 0.001), clinical stage (P < 0.001), differentiation (P < 0.05), and poor clinical outcome (P < 0.05) in OSCC patients. Furthermore, univariate and multivariate analyses revealed that high DOCK6 expression (P < 0.01) and clinical stage III-IV (P < 0.05) might serve as independent prognostic factors for OSCC patients. Functionally, DOCK6 silencing significantly suppressed OSCC cell migration and invasion (all P < 0.05). Ten proteins that interact with DOCK6, more than ten functions related to cancer, and more than six pathways related to DOCK6 in OSCC were identified via bioinformatic methods. CONCLUSION: DOCK6 is upregulated in OSCC, is associated with a poor prognosis in OSCC patients and increases OSCC cells migration and invasion. These findings suggest that DOCK6 may be a potential therapeutic target with prognostic implication in patients with OSCC.

Matrine increases the inhibitory effects of afatinib on H1975 cells via the IL­6/JAK1/STAT3 signaling pathway.

Resistance to epidermal growth factor receptor (EGFR) inhibitors is of primary concern in the treatment of non­small­cell lung cancer (NSCLC) with EGFR mutations. To investigate the effects of matrine on H1975 cells and to examine a novel, potential treatment option for NSCLC, the present study measured cell viability, apoptotic rate, interleukin 6 (IL­6) expression and activation of the janus kinase (JAK) 1/signal transducer and activator of transcription (STAT)3 signaling pathway in cells treated with or without matrine, in the presence or absence of afatinib. The results demonstrated that matrine treatment inhibited cell growth, decreased B­cell lymphoma 2 (Bcl­2) expression and induced apoptosis. Matrine treatment additionally decreased the mRNA and protein levels of IL­6 and inhibited activation of the JAK1/STAT3 signaling pathway in H1975 cells in a dose­dependent manner. H1975 cells treated with IL­6 small interfering RNA exhibited a decrease in Bcl­2 expression levels and cell viability. Treatment with a combination of matrine and afatinib demonstrated increased inhibitory effects on the growth rate of H1975 cells. The findings of the present study suggested that matrine treatment decreases IL­6 expression, inhibits activation of the JAK1/STAT3 signaling pathway, reduces the expression levels of Bcl­2 and inhibits cell growth. Furthermore, matrine treatment was demonstrated to increase the inhibitory effects of afatinib on H1975 cells with the T790M EGFR mutation.

The effect of nuclear factor of activated T-cells (NFAT) in kidney I/R mediated by C5a/C5aR.

To investigate the relationship between NFAT and C5a/C5aR in C5a/C5aR-mediated kidney Ischemia/reperfusion (I/R) injury, the rats' NRK-52E cell line was used in this study and was distributed into 4 groups, I: the normal control (NC), II: the ischemia/reperfusion (I/R) injury cell model (MG), III: the ischemia/reperfusion (I/R) injury cell model treated with C5a (50 nmol/l) (MG + C5a), IV: the ischemia/reperfusion (I/R) injury cell model treated with C5aR antagonist (2.5 µmol/l) (MG + anti-C5aR). Reverse transcription polymerase chain reaction (RT-PCR), western blot, immunofluorescence and flow cytometry were performed. Nuclear Factor Activated T Cell (NFAT), tumor necrosis factor-α (TNF-α) and interleukin (IL-6) were detected in this study. The results of immunofluorescence showed that NFAT had a nuclear translocation phenomenon during the study. The RT-PCR and WB data indicated that the expression of TNF-α and IL-6 in group III were higher than any other groups. Apoptosis in group III was much serious than other groups. All the results in this study showed that NFAT plays an important role in ischemia/reperfusion injury, it can be induced to up-regulate the inflammatory factor TNF-α and IL-6 by the complement system member C5a/C5aR.

[Thoracic involvement of Castleman's disease: report of 10 cases].

OBJECTIVE: To improve the recognition of thoracic involvement of Castleman' s disease. METHODS: Ten patients with thoracic involvement of Castleman' s disease were retrospectively studied by review of the clinical manifestations, radiology, pathology, differential diagnosis, therapy and prognosis. RESULTS: The 10 patients were all females. Five of the patients, aged from 29 to 49 years, presented with multicentric lesions, manifested by interstitial pneumonia and mediastinal lymphadenopathy on radiology, as well as extrathoracic involvement including peripheral lymphadenopathy, and multiple organ impairment. The pathology was the plasma cell type. Treatment with corticosteroids and chemotherapy achieved partial remission in 4 cases, but 1 died of cardiac and respiratory failure. Localized lesions were found in the other 5 patients, aged from 13 to 49 years. No specific manifestations were revealed in these patients. The major radiological sign was right mediastinal masses, 6-9 cm in diameter, uniformly enhanced by contrast radiology. The pathology revealed vascular hyaline degeneration. Early surgical resection achieved good prognosis. The 5 patients were all alive. CONCLUSIONS: Diagnosis of thoracic involvement of Castleman' s disease is not easy. Early, repeated and multiple biopsy of lymph nodes is recommended, especially when the disease is multicentric or when the lymph nodes are massive. Synchronous enhancement with the vessels on contrast radiology is suggestive of the diagnosis.