Int J Med Sci
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Objectives: IL-17 modulates the synthesis of several molecules involved in the pathogenesis of Systemic Sclerosis (SSc). Vitamin D (1,25(OH)2D3) shows anti-fibrotic properties and it is able to affect the IL-17 production in several experimental conditions. The aim of this study is to assess the production of IL-17A and pro-fibrotic cytokines in peripheral blood mononuclear cells (PBMCs) from subjects with SSc in basal conditions and after treatment with 1,25(OH)2D3 and IL-17A neutralizing antibodies. ⋯ IL17, TGFβ, CTGF and FGF2 levels were higher in SSc patients with interstitial lung disease and digital ulcers, whereas IL-17A production was lower in patients with PAH. IL- 17A inhibition reduced the production of FGF2, whereas enhanced the synthesis of TGFβ and CTGF. 1,25(OH)2D3 decreased the production of IL17A and pro-fibrotic cytokines in a dose- dependent manner. Conclusions: IL-17A is involved in the regulation of fibrogenesis in SSc, and could represent an intriguing potential therapeutic target, even if its role remains controversial. 1,25(OH)2D3 inhibits both IL-17A and pro-fibrotic cytokines, confirming its potential anti-fibrotic effect.
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COVID-19 clinically manifests from asymptomatic to the critical range. Immune response provokes the pro-inflammatory interactions, which lead to the cytokines, reactive oxygen/nitrogen species, peptidases, and arachidonic acid metabolites enlargement and activation of coagulation components. Matrix metalloproteinases (MMPs) contribute to tissue destruction in the development of COVID-19. ⋯ Testing the capability of this ratio to predict the COVID-19 stage by ROC curves, we found the MMP-9/BDNF could be a suitable marker for differentiating stages I/II (AUC 0.7597), stage I/III (AUC 0.9011), and stage I/IV (AUC 0.7727). Presented data describe for the first time the high-level systemic MMP-9/BDNF ratio in patients with COVID-19. This parameter could contribute to a more precise determination of the phase of the disease.
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Single nucleotide polymorphisms (SNPs) of tissue inhibitor of metalloproteinases-3 (TIMP-3) have been revealed to be related to various cancers. To date, no study explores the relationships between TIMP-3 polymorphisms and uterine cervical cancer. The purposes of this research were to investigate the associations among genetic variants of TIMP-3 and development and clinicopathological factors of uterine cervical cancer, and patient 5 years survival in Taiwanese women. ⋯ Moreover, it revealed that cervical cancer patients carrying genotypes CC in rs9619311 exhibited a poorer 5 years survival, as compared to those with TT/TC in Taiwanese women, using univariate analysis. In addition, pelvic lymph node metastasis was determined to independently predict 5 years survival in cervical cancer patients using multivariate analysis. Conclusively, TIMP-3 SNPs polymorphisms rs9619311 are related to cervical patient survival in Taiwanese women.
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Renal cancer incidence has been increasing across the world, clear cell renal cell carcinoma (ccRCC) represents the major subtype of renal cancer. The proteasome is involved in onset, metabolism and survival of tumor and has been recognized as a therapeutic target for various malignancies, while the role of β subunits of proteasome, PSMB gene family, in ccRCC has not been fully unveiled. Herein we investigated the expression and the prognostic role of PSMBs in ccRCC by analyzing a series of databases, including ONCOMINE, UALCAN, cBioPortal, STRING, GEPIA, GO and KEGG. ⋯ Further, high mRNA levels of PSMB1/2/3/4/6/10 were correlated with shorter overall survival in univariate analysis. Taken together, the results of our analysis implied that overexpression of PSMB1/2/3/4/6/8/9/10 were indicative of worse prognosis of ccRCC. However, further researches were required to validate our findings.
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Osteosarcoma is the most common malignant tumor in adolescent bone malignancies. It has the characteristics of a high metastasis rate, high mortality and poor prognosis. As a subclass of endogenous noncoding RNAs, circRNAs have been identified to be related to the occurrence, development and prognosis of different kinds of cancers, but the mechanism of their effect on osteosarcoma is not clear. ⋯ Furthermore, Western blotting experiments demonstrated that hsa_circ_0087302 affected the expression of cell cycle- and Wnt/β-catenin signaling pathway-related proteins. For the first time, we identified that hsa_circ_0087302 may affect the malignant biological behavior of osteosarcoma cells through the Wnt/β-catenin signaling pathway. In summary, hsa_circ_0087302 may provide a new direction for the diagnosis and treatment of osteosarcoma.