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- Gupta, S, et al.
(författare)
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Dynamical modeling of miR-34a, miR-449a, and miR-16 reveals numerous DDR signaling pathways regulating senescence, autophagy, and apoptosis in HeLa cells
- 2022
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1, s. 4911-
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Tidskriftsartikel (refereegranskat)abstract
- Transfection of tumor suppressor miRNAs such as miR-34a, miR-449a, and miR-16 with DNA damage can regulate apoptosis and senescence in cancer cells. miR-16 has been shown to influence autophagy in cervical cancer. However, the function of miR-34a and miR-449a in autophagy remains unknown. The functional and persistent G1/S checkpoint signaling pathways in HeLa cells via these three miRNAs, either synergistically or separately, remain a mystery. As a result, we present a synthetic Boolean network of the functional G1/S checkpoint regulation, illustrating the regulatory effects of these three miRNAs. To our knowledge, this is the first synthetic Boolean network that demonstrates the advanced role of these miRNAs in cervical cancer signaling pathways reliant on or independent of p53, such as MAPK or AMPK. We compared our estimated probability to the experimental data and found reasonable agreement. Our findings indicate that miR-34a or miR-16 may control senescence, autophagy, apoptosis, and the functional G1/S checkpoint. Additionally, miR-449a can regulate just senescence and apoptosis on an individual basis. MiR-449a can coordinate autophagy in HeLa cells in a synergistic manner with miR-16 and/or miR-34a.
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- Samal, SK, et al.
(författare)
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Antibodies against Malondialdehyde in Haemodialysis Patients and Its Association with Clinical Outcomes: Differences between Subclasses and Isotypes
- 2020
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Patients on haemodialysis (HD-patients) have an increased risk of premature death. Low levels of IgM antibodies against malondialdehyde (anti-MDA) are associated with increased risk of cardiovascular disease (CVD) with underlying potential mechanisms described. Here, we studied subclasses and isotypes of anti-MDA in 210 HD-patients with mortality as outcome (56% men, median age 66, Interquartile range (IQR) 51–74 years, vintage time 29 (15–58) months, mean follow up period of 41 (20–60)months). Patients were also divided into inflamed c-reactive protein (CRP >5.6 mg/mL) and non-inflamed. Antibody levels were measured by ELISA. In multivariate risk analysis, patients in low tertile of IgM anti-MDA sub-distribution hazard ratio (sHR 0.54); 95% confidence interval (CI: 0.34–0.89) inversely and significantly associated with all-cause mortality after five years, after adjusting for confounders. Low tertile of IgG (sHR 0.48, 95%CI: 0.25–0.90, p = 0.02) and IgG1 (sHR 0.50, CI: 0.24–1.04, p = 0.06) was associated low mortality among non-inflamed patients. In contrast, anti-MDA IgG2 among inflamed patients was significantly associated with increased mortality, IgG2(sHR 2.33, CI: 1.16–4.68, p = 0.01). IgM anti-MDA was a novel biomarker among HD-patients with low levels being associated with mortality, while low levels of IgG and IgG1 but not IgA anti-MDA were associated with mortality only among non-inflamed patients. IgG2 anti-MDA was a significant risk marker among inflamed patients, which could be related to infection.
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- Samal, SK, et al.
(författare)
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Different subclasses and isotypes of antibodies against phosphorylcholine in haemodialysis patients: association with mortality
- 2020
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Ingår i: Clinical and experimental immunology. - : Oxford University Press (OUP). - 1365-2249 .- 0009-9104. ; 201:1, s. 94-104
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Tidskriftsartikel (refereegranskat)abstract
- The risk of premature death is high among patients on haemodialysis (HD patients). We previously determined that immunoglobulin (Ig)M antibodies against phosphorylcholine (anti-PC) are negatively associated with increased risk of cardiovascular disease (CVD), atherosclerosis, some autoimmune diseases and mortality among HD patients in this cohort. Here, we also study other subclasses and isotypes of anti-PC in HD patients in relation to mortality, inflammation and gender. The study group is a cohort of 209 prevalent HD patients [median age = 66 years, interquartile range (IQR) = 51–74], vintage time = 29 months (IQR = 15–58; 56% men) with a mean follow-up period of 41 months (IQR = 20–60). Fifty-six per cent were men. We also divided patients into inflamed C-reactive protein (CRP) > 5·6 mg/ml and non-inflamed CRP. Antibody levels were determined by in-house enzyme-linked immunosorbent assay. IgG1 anti-PC below median was significantly associated with increased all-cause mortality (after adjustment for confounders: P = 0·02), while IgG, IgA and IgG2 anti-PC were not associated with this outcome. Among non-inflamed patients, IgM and IgG1 anti-PC were significantly associated with mortality (P = 0·047 and 0·02). IgG1 anti-PC was significantly associated with mortality among men (P = 0·03) and trending among women (P = 0·26). IgM (as previously reported) and IgG1 anti-PC are negatively associated with survival among HD patients and non-inflamed HD patients, but among inflamed patients there were no associations. IgG, IgA or IgG2 anti-PC were not associated with survival in these groups and subgroups. Further studies are needed to determine if raising anti-PC levels, especially IgM and IgG1 anti-PC, through immunization is beneficial.
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