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- Nissinen, N. M., et al.
(författare)
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Financial difficulties among youth prenatally exposed to substances: a longitudinal register-based cohort study
- 2023
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Ingår i: Drugs-Education Prevention and Policy. - : Informa UK Limited. - 0968-7637 .- 1465-3370.
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Tidskriftsartikel (refereegranskat)abstract
- AimThe receipt of long-term financial social assistance (FSA) as an indicator of financial difficulties among Finnish youth with prenatal substance exposure (PSE) was investigated in comparison with unexposed youth.MethodsData from national health and social welfare registers were collected for 18-24-year-old exposed (n = 355) and unexposed (n = 1011) youth. The influence of youth and maternal characteristics and out-of-home care (OHC) on the association between PSE and youth's long-term FSA receipt was studied by generalized linear models and mediation analyses.ResultsExposed youth had an increased likelihood of long-term FSA receipt (OR 4.89, 95% CI 3.76, 6.37) but the difference with unexposed was attenuated following adjustments for youth and maternal characteristics and OHC (AOR 1.33, 95% CI 0.89, 1.98). Maternal long-term FSA receipt (0.48, 95% CI 0.35, 0.64) and OHC (0.63, 95% CI 0.47, 0.83) mediated a large proportion of the association between PSE and youth's long-term FSA receipt. Youth's mental or behavioral disorders partly mediated the association (0.21, 95% CI 0.14, 0.30), but the mediating effect of lack of secondary education was minor (0.03, 95% CI 0.01, 0.07).ConclusionReceipt of long-term FSA among youth with PSE likely reflects maternal substance abuse linked with maternal financial situation and care instability in childhood.
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| 2. |
- Piipponen, M, et al.
(författare)
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Super Enhancer-Regulated LINC00094 (SERLOC) Upregulates the Expression of MMP-1 and MMP-13 and Promotes Invasion of Cutaneous Squamous Cell Carcinoma
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:16
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Tidskriftsartikel (refereegranskat)abstract
- Long non-coding RNAs (lncRNAs) have emerged as important regulators of cancer progression. Super enhancers (SE) play a role in tumorigenesis and regulate the expression of specific lncRNAs. We examined the role of BRD3OS, also named LINC00094, in cutaneous squamous cell carcinoma (cSCC). Elevated BRD3OS (LINC00094) expression was detected in cSCC cells, and expression was downregulated by SE inhibitors THZ1 and JQ1 and via the MEK1/ERK1/2 pathway. Increased expression of BRD3OS (LINC00094) was noted in tumor cells in cSCCs and their metastases compared to normal skin, actinic keratoses, and cSCCs in situ. Higher BRD3OS (LINC00094) expression was noted in metastatic cSCCs than in non-metastatic cSCCs. RNA-seq analysis after BRD3OS (LINC00094) knockdown revealed significantly regulated GO terms Cell-matrix adhesion, Basement membrane, Metalloendopeptidase activity, and KEGG pathway Extracellular matrix–receptor interaction. Among the top-regulated genes were MMP1, MMP10, and MMP13. Knockdown of BRD3OS (LINC00094) resulted in decreased production of MMP-1 and MMP-13 by cSCC cells, suppressed invasion of cSCC cells through collagen I, and growth of human cSCC xenografts in vivo. Based on these observations, BRD3OS (LINC00094) was named SERLOC (super enhancer and ERK1/2-Regulated Long Intergenic non-protein coding transcript Overexpressed in Carcinomas). These results reveal the role of SERLOC in cSCC invasion and identify it as a potential therapeutic target in advanced cSCC.
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| 4. |
- Koponen, AM, et al.
(författare)
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Adverse childhood experiences and neurodevelopmental disorders among youth with and without prenatal substance exposure: A longitudinal matched register-based cohort study
- 2023
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Ingår i: Nordisk alkohol- & narkotikatidskrift : NAT. - : SAGE Publications. - 1458-6126. ; 40:2, s. 176-198
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous research has shown an association between adverse childhood experiences (ACEs) and secondary mental health problems in youth with prenatal substance exposure (PSE), but the association between ACEs and neurodevelopmental disorders is less clear. Methods: This longitudinal register-based cohort study investigated relationships between health at birth, ACEs (out-of-home care (OHC) and maternal adversities), and neurodevelopmental disorders among youth with PSE (alcohol/drugs, n = 615) and matched unexposed controls ( n = 1787). Hospital medical records and register data were merged and analysed using Cox regression models. Results: Conduct and emotional disorders (International Statistical Classification of Diseases and Related Health Problems ICD-10, F90–F94) were more common among the exposed than the controls but only when the exposed and controls with no OHC were compared. The difference appeared in hyperkinetic disorders (ADHD, F90), mixed disorders of conduct and emotions (F92) and emotional disorders with onset specific to childhood (F93). Among the exposed and controls with OHC, over 40% had received an F90–F94 diagnosis. Regarding specific developmental disorders (F80–F83, e.g., impairments in speech and language and scholastic skills) the moderate difference between the exposed and controls attenuated after adjustment for OHC. Again, the rates were highest among the exposed with OHC and the controls with OHC. OHC and maternal risks were interrelated and, together with male sex and low birth weight, were associated with neurodevelopmental disorders both among the exposed and controls and decreased the difference between them. Conclusions: A strong association between ACEs and neurodevelopmental disorders was found. Brain research is needed to examine whether ACEs worsen neurodevelopmental outcomes caused by PSE.
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| 10. |
- Pennanen, P., et al.
(författare)
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Signaling pathways in human osteoclasts differentiation: ERK1/2 as a key player
- 2021
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Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 48, s. 1243-1254
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the signaling pathways involved in the differentiation of human osteoclasts. The present study evaluated the roles of the Ras/PI3K/Akt/mTOR, Ras/Raf/MEK1/2/ERK1/2, calcium-PKC, and p38 signaling pathways in human osteoclast differentiation. Mononuclear cells were isolated from the peripheral blood of control persons and patients with neurofibromatosis 1 (NF1), and the cells were differentiated into osteoclasts in the presence of signaling pathway inhibitors. Osteoclast differentiation was assessed using tartrate-resistant acid phosphatase 5B. Inhibition of most signaling pathways with chemical inhibitors decreased the number of human osteoclasts and disrupted F-actin ring formation, while the inhibition of p38 resulted in an increased number of osteoclasts, which is a finding contradictory to previous murine studies. However, the p38 inhibition did not increase the bone resorption capacity of the cells. Ras-inhibitor FTS increased osteoclastogenesis in samples from control persons, but an inhibitory effect was observed in NF1 samples. Inhibition of MEK, PI3K, and mTOR reduced markedly the number of NF1-deficient osteoclasts, but no effect was observed in control samples. Western blot analyses showed that the changes in the phosphorylation of ERK1/2 correlated with the number of osteoclasts. Our results highlight the fact that osteoclastogenesis is regulated by multiple interacting signaling pathways and emphasize that murine and human findings related to osteoclastogenesis are not necessarily equivalent.
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| 11. |
- Piipponen, M, et al.
(författare)
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The Role of p53 in Progression of Cutaneous Squamous Cell Carcinoma
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:18
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Tidskriftsartikel (refereegranskat)abstract
- Skin cancers are the most common types of cancer worldwide, and their incidence is increasing. Melanoma, basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (cSCC) are the three major types of skin cancer. Melanoma originates from melanocytes, whereas BCC and cSCC originate from epidermal keratinocytes and are therefore called keratinocyte carcinomas. Chronic exposure to ultraviolet radiation (UVR) is a common risk factor for skin cancers, but they differ with respect to oncogenic mutational profiles and alterations in cellular signaling pathways. cSCC is the most common metastatic skin cancer, and it is associated with poor prognosis in the advanced stage. An important early event in cSCC development is mutation of the TP53 gene and inactivation of the tumor suppressor function of the tumor protein 53 gene (TP53) in epidermal keratinocytes, which then leads to accumulation of additional oncogenic mutations. Additional genomic and proteomic alterations are required for the progression of premalignant lesion, actinic keratosis, to invasive and metastatic cSCC. Recently, the role of p53 in the invasion of cSCC has also been elucidated. In this review, the role of p53 in the progression of cSCC and as potential new therapeutic target for cSCC will be discussed.
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