The significance of serum IgG4 and CA19-9, autoantibodies in diagnosis and differential diagnosis of IgG4-related sclerosing cholangitis.

OBJECTIVE: To investigate the value of serum levels of IgG4 and CA19-9, and autoantibodies in the diagnosis of IgG4-related sclerosing cholangitis (IgG4-SC). METHODS: We detected the serum IgG4 and CA19-9 of 45 IgG4-SC patients, 173 non-IgG4-SC patients and 48 healthy controls by immunoassay and chemiluminescence, respectively, with antinuclear antibody (ANA), anti-neutrophil antibody (ANCA), anti-smooth muscle antibody (SMA) and anti-mitochondrial antibody (AMA) level detected by indirect immunofluorescence. Then analyze the detection results. RESULTS: (1) The positive rates of ANA, ANCA, SMA and AMA in patients with IgG4-SC were 40%, 6.67%, 0 and 2.22%. Among them, the positive rate of ANA was significantly higher than that of the healthy control group (p < .01), and the positive rate of ANA, ANCA, SMA and AMA were significantly different from that of the non-IgG4-SC group (p < .05). (2) Serum levels of IgG4 and CA19-9 increased significantly in patients with IgG4-SC compared with the healthy controls (p < .01). The areas under the ROC curve (AUC) of IgG4 and CA19-9 were 0.9750 and 0.6498, respectively (p < .05). CONCLUSION: The high levels of serum IgG4 and CA19-9, and autoantibodies detections are of great important clinical value in diagnosis and differential diagnosis of IgG4-SC.

Downregulated CDK10 promotes cancer progression and radioresistance in lung cancer through activating the JNK/c-Jun signaling pathway.

Lung cancer is one of the most significant malignancies, with both high morbidity and mortality. CDK10 is closely related to cancer progression and metastasis. However, its role in lung cancer radioresistance demands further clarification. In this study, we demonstrated that CDK10 was downregulated in lung cancer tissues, and CDK10 expression level was associated with the clinical prognosis in lung cancer patients. We also found that silencing CDK10 promoted lung cancer cell proliferation, migration, and radioresistance. We further verified that silencing CDK10 facilitated the activation of JNK/c-Jun signaling, and c-Jun depletion could reverse the effects of CDK10 knockdown in lung cancer cells. Our findings revealed that CDK10 plays an important role in cell growth and radioresistance by inhibiting JNK/c-Jun signaling pathway in lung cancer. Therefore, CDK10 might be a promising therapeutic target in lung cancer.

Acidosis activates breast cancer ferroptosis through ZFAND5/SLC3A2 signaling axis and elicits M1 macrophage polarization.

Acidosis is involved in multiple pathways in tumor cells and immune cells among the tumor microenvironment (TME). Ferroptosis is a nonapoptotic and iron-dependent form of cell death characterized by accumulation of lipid peroxidation involved in various cancers. The role of ferroptosis in the breast cancer (BC) acidic microenvironment remains unrevealed. Here, we reported that short-term acidosis induced ferroptosis of BC cells in the zinc finger AN1-type domain 5 (ZFAND5)/solute carrier family 3 member 2 (SLC3A2) dependent manner to suppress tumor growth using in silico and multiple biological methods. Mechanistically, we demonstrated that short-term acidosis increased total/lipid reactive oxygen species (ROS) level, decreased glutathione (GSH) level and induced the morphological changes of mitochondria. Specifically, acidosis restrained the protein stability of SLC3A2 by promoting its ubiquitination process. The prognostic analysis showed that higher expression of ZFAND5 and lower expression of SLC3A2 were correlated with longer overall survival of BC patients, respectively. Furthermore, in combination with ferroptosis agonist metformin, short-term acidosis could synergistically inhibit viability and enhance the ferroptosis of BC cells. Meanwhile, by the exploration of immune cells, short-term acidosis also induced M1 macrophage polarization, triggering processes of phagocytosis and ferroptosis in BC cells. This study demonstrated that short-term acidosis induced BC cell ferroptosis through ZFAND5/SLC3A2 signaling axis and promoted phagocytosis and ferroptosis of BC cells with M1 macrophage polarization, which might be a new mechanism for BC therapy.

Roles of USP9X in cellular functions and tumorigenesis (Review).

Ubiquitin-specific peptidase 9X (USP9X) is involved in certain human diseases, including malignancies, atherosclerosis and certain diseases of the nervous system. USP9X promotes the deubiquitination and stabilization of diverse substrates, thereby exerting a versatile range of effects on pathological and physiological processes. USP9X serves vital roles in the processes of cell survival, invasion and migration in various types of cancer. The present review aims to highlight the current knowledge of USP9X in terms of its structure and the possible mediatory mechanisms involved in certain types of cancer, providing a thorough introduction to its biological functions in carcinogenesis and further outlining its oncogenic or suppressive properties in a diverse range of cancer types. Finally, several perspectives regarding USP9X-targeted pharmacological therapeutics in cancer development are discussed.

Clinical significance of detecting HLA-DR, 14-3-3η protein and d-dimer in the diagnosis of rheumatoid arthritis.

AIM: To investigate the clinical significance of detecting several biomarkers collectively in the diagnosis of rheumatoid arthritis (RA). METHODS: 128 RA patients, 174 non-RA patients and 80 healthy controls were enrolled. HLA-DR4 and HLA-DR53 were detected by the PCR-SSP method, 14-3-3η protein, anti-CCP and anti-Sa were detected by ELISA and DD was detected by latex immunoturbidimetric assay. RESULTS: The positive rates of HLA-DR4, HLA-DR53, 14-3-3η protein, anti-CCP and anti-Sa were obviously higher in the RA group (43.8, 38.3, 51.6, 80 and 40.6%, respectively); anti-CCP was of highest sensitivity (79.68%), highest specificity (97.5%) and Youden index (0.77). The AUC of 14-3-3η protein, DD, anti-CCP, anti-Sa were 0.813, 0.859, 0.930, 0.861, respectively. CONCLUSION: All biomarkers were strongly correlated risk factors for RA; the combination of multiple biomarkers might be of help for diagnostic and therapeutic strategies in RA of recent onset.

Diagnostic Value of Vitamin D Status and Bone Turnover Markers in Rheumatoid Arthritis Complicated by Osteoporosis.

OBJECTIVE: To research the diagnostic performance of clinical potential bone turnover indexes in rheumatoid arthritis (RA) complicated with osteoporosis (OP). METHODS: This study involved 87 RA patients, 48 with OP, and 39 without OP, and 204 non-RA control patients, including those with systemic lupus erythematosus, ankylosing spondylitis, primary Sjogren's syndrome, systemic sclerosis, and healthy patients. The levels of 25-hydroxyvitamin D [25(OH)D], ß-crosslaps (ß-CROSSL), parathyroid hormone (PTH) were measured by electrochemiluminescence (ECLIA), and the level of bone alkaline phosphatase (BALP) was measured by lectin affinity method. RESULTS: The serum concentration of 25(OH)D in the RA with OP group was significantly lower than the control group (P<0.01), while the levels of ß-CROSSL, BALP in the RA with OP group considerably exceeded those found in the control group (P<0.01). The levels of ß-CROSSL and PTH were significantly higher in RA patients with OP than without OP (P<0.01), while the level of 25(OH)D was statistically lower than without OP (P<0.01). An unconditional logistical regression analysis proved an association with low 25(OH)D and elevated ß-CROSSL in RA with OP, with 25(OH)D demonstrating greatest diagnostic potential according to the ROC curve. CONCLUSION: The significantly reduced levels of 25(OH)D and excessive ß-CROSSL may indicate a high risk of the secondary osteoporosis in RA patients.