Int J Med Sci
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N6-methyladenosine (m6A) RNA methylation has been implicated in various malignancies. This study aimed to identify prognostic signature based on m6A methylation regulators for hepatocellular carcinoma (HCC) and provide candidate targets for HCC treatment. In this study, the expression levels, prognostic values, correlation with tumor grades and genetic variations of m6A-related genes in HCC were evaluated using bioinformatics analyses. ⋯ Functional and pathway enrichment analyses indicated that ZC3H13 might be involved in transcriptional dysregulation or the JAK-STAT signaling pathway in cancer. Additionally, ZC3H13 expression was significantly correlated with lymphocytes and immunomodulators. Therefore, ZC3H13 is a promising candidate as a novel biomarker and therapeutic target for HCC.
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Background: SARS-CoV-2 infection causes immune response and produces protective antibodies, and these changes may persist after patients discharged from hospital. Methods: This study conducted a one-year follow-up study on patients with COVID-19 to observe the dynamic changes of circulating leukocyte subsets and virus-specific antibodies. Results: A total of 66 patients with COVID-19 and 213 healthy patients with inactivated SARS-CoV-2 vaccination were included. ⋯ The counts of CD4+ and CD8+ T, B and NK cells increased with the time of recovery, and remained basically stable from 9 to 12 months after discharge. After 12 months, the positivity of IgG antibody was 85.3% and IgM was 11.8%, while the virus-specific antibody changed dynamically in patients within one year after discharge. Conclusions: The SARS-CoV-2 specific antibody of recovered patients showed dynamic fluctuation after discharge, while the leukocyte subsets gradually increased and basically stabilized after 9 months.
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Human fibroleukin 2 (Fgl2), a member of the fibrinogen superfamily, can cleave prothrombin to generate thrombin or is secreted in a soluble form as a new type of effector of Tregs with immunomodulatory functions. However, there is little research on the role of Fgl2 in cutaneous squamous cell carcinoma (CSCC) growth. We examined the expression of Fgl2 in samples from CSCC patients and CSCC cell lines. ⋯ Knocking down Fgl2 reduced CSCC cell proliferation and inhibited autophagy in CSCC. Mechanistically, Fgl2 interacted with Tyrobp and promoted ERK-dependent autophagy, resulting in the proliferation of CSCC cells. Our study suggested that Fgl2 could be a promising prognostic biomarker and useful therapeutic target for CSCC.
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Chronic Venous Disease (CVD) refers to a wide variety of venous disorders being the varicose veins its most common manifestation. It is well-established the link between pregnancy and the risk of suffering CVD, due to hormonal or haematological factors, especially during the third trimester. In the same manner, previous studies have demonstrated the detrimental effect of this condition in the placental tissue of pregnant women, including in the normal physiology and the metabolomic profile of this organ. ⋯ Our results have reported a significative increase in the expression of GLUT-1, PGK1, ALD, GA3PDH and the isoenzyme LDHA in placentas of women with CVD. This work has proven for the first-time an altered glucose metabolism in the placental tissue of women affected by CVD, what may aid to understand the pathophysiological mechanisms of this condition in more distant organs such as placenta. Furthermore, our research also supports the basis for further studies in the metabolic phenotyping of the human placenta due to CVD, which may be considered during the late pregnancy in these women.
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Abnormally decreased renal Klotho is linked to endoplasmic reticulum-associated degradation in mice.
Aim: Endoplasmic reticulum-associated degradation (ERAD), which involves degradation of improperly folded proteins retained in the ER, is implicated in various diseases including chronic kidney disease. This study is aimed to determine the role of ERAD in Klotho deficiency of mice and human kidney tubular epithelial cells (HK-2) with renal interstitial fibrosis (RIF). Methods: Following establishment of a mouse RIF model by unilateral ureteral obstruction (UUO), a specific ERAD inhibitor, Eeyarestatin I (EerI), was administered to experimental animals by intraperitoneal injection. ⋯ These observations suggest that UPR was remarkably enhanced in the presence of ERAD inhibition and compensated for excess improperly folded proteins, subsequently contributing to the additional production of mature Klotho protein. Conclusion: ERAD is involved in Klotho deficiency in RIF and its specific inhibition significantly promoted Klotho expression, possibly through enhanced UPR. This may represent a novel regulatory mechanism and new therapeutic target for reversing Klotho deficiency.