Int J Med Sci
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Objective: To identify the interaction between the MYOC Y437H mutation and TGF-β2 in a family with primary open-angle glaucoma (POAG). Methods: The MYOC Y437H mutation was identified in a family with POAG; the family was a fourth-generation family with 27 members, of which 6 members were affected. Analysis focused on the secreted myocilin protein and TGF-β2 found in the aqueous humor. ⋯ This increase in TGF-β2 was also associated with increased cell death in cells carrying the MYOC Y437H mutation. Conclusion: These data collectively suggest that the mutual interaction between glaucomatous MYOC mutation and TGF-β2 contributed to the cell death of TM cells. This relationship also provides a new, therapeutic targets for the treatment of glaucoma.
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Background: Patients with chronic kidney disease (CKD) are associated with high prevalence rates of proteinuria, vascular calcification and cardiomegaly. In this study, we investigated relationships among proteinuria, aortic arch calcification (AoAC) and cardio-thoracic ratio (CTR) in patients with CKD stage 3A-5. In addition, we investigated correlations among proteinuria and decline in renal function, overall and cardiovascular (CV) mortality. ⋯ Multivariable analysis showed that a high UPCR was associated with high AoAC (unstandardized coefficient β: 0.315; p = 0.002), high CTR (unstandardized coefficient β: 1.186; p = 0.028) and larger negative eGFR slope (unstandardized coefficient β: -2.398; p < 0.001). With regards to clinical outcomes, a high UPCR was significantly correlated with progression to dialysis (log per 1 mg/g; hazard ratio [HR], 2.538; p = 0.003), increased overall mortality (log per 1 mg/g; HR, 2.292; p = 0.003) and increased CV mortality (log per 1 mg/g; HR, 3.195; p = 0.006). Conclusions: Assessing proteinuria may allow for the early identification of high-risk patients and initiate interventions to prevent vascular calcification, cardiomegaly, and poor clinical outcomes.
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Cardiomyocyte autophagy plays an important role in myocardial ischemia-reperfusion injury (MIRI). P300/CBP-associated factor (PCAF) was involved in the regulation of autophagy. However, the role of PCAF in MIRI is currently unknown. ⋯ Wortmannin, a PI3K/Akt inhibitor, could abrogate the effects of downregulation of PCAF on cardiomyocytes autophagy. These results demonstrated that downregulation of PCAF alleviated MIRI by inhibiting cardiomyocyte autophagy through PI3K/Akt/mTOR signaling pathway. Thus, PCAF may be a potential target for prevention and treatment of MIRI.
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Circular RNAs (circRNAs), a new kind of non-coding RNAs, have gradually been proved to be critical regulators of gene expression; however, the underlying mechanisms still need to be elaborated. In the present study, we investigated the role of hsa-circ-0007766 in gastric carcinoma (GC). Quantitative real-time PCR was applied to detect the differential expression levels of circRNA, miRNAs, and mRNAs in human tissues and specific cell lines. ⋯ Moreover, hsa-circ-0007766 was identified as a sponge of miR-1233-3p, which could target gene GDF15 to regulate the progression of GC. Finally, hsa-circ-0007766 was evaluated to be a valuable diagnostic marker with a sensitivity of 53.33% and specificity of 83.33% by ROC analysis. This study unveils a mechanism by which hsa-circ-0007766 regulates GDF15 via hsa-circ-0007766/miR-1233-3p/GDF15 axis, which may provide new insight for GC therapeutic strategies.
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Background: Gallbladder cancer (GBC) is the most common malignancy of the biliary system. Early T stage GBC patients with distant metastasis are proven to have a worse prognosis. In this study, our aim was to construct and validate a novel nomogram for predicting distant metastasis in T1 and T2 GBC. ⋯ Through ROC curve analysis, the areas under the ROC curves in the training and validation cohorts were 0.723 and 0.679, respectively. Conclusions: Although some limitations exist in this predictive model, the nomogram revealed the relationship between the clinicopathological characteristics of T1 and T2 GBC patients and the risk of distant metastasis. The novel nomogram will assist in patient counseling and guide treatment decision making for T1 and T2 GBC patients.