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Diaz Cruz, M. A., Lund, D., Szekeres, F., Karlsson, S., Faresjö, M. & Larsson, D. (2021). Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems. Open Medicine (Poland), 16(1), 640-650
Open this publication in new window or tab >>Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
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2021 (English)In: Open Medicine (Poland), ISSN 2391-5463, Vol. 16, no 1, p. 640-650Article in journal (Refereed) Published
Abstract [en]

Nuclear receptors (NRs) are ligand-activated transcription factors that regulate gene expression when bound to specific DNA sequences. Crosstalk between steroid NR systems has been studied for understanding the development of hormone-driven cancers but not to an extent at a genetic level. This study aimed to investigate crosstalk between steroid NRs in conserved intron and exon sequences, with a focus on steroid NRs involved in prostate cancer etiology. For this purpose, we evaluated conserved intron and exon sequences among all 49 members of the NR Superfamily (NRS) and their relevance as regulatory sequences and NR-binding sequences. Sequence conservation was found to be higher in the first intron (35%), when compared with downstream introns. Seventy-nine percent of the conserved regions in the NRS contained putative transcription factor binding sites (TFBS) and a large fraction of these sequences contained splicing sites (SS). Analysis of transcription factors binding to putative intronic and exonic TFBS revealed that 5 and 16%, respectively, were NRs. The present study suggests crosstalk between steroid NRs, e.g., vitamin D, estrogen, progesterone, and retinoic acid endocrine systems, through cis-regulatory elements in conserved sequences of introns and exons. This investigation gives evidence for crosstalk between steroid hormones and contributes to novel targets for steroid NR regulation. 

Place, publisher, year, edition, pages
De Gruyter Open, 2021
Keywords
conserved sequences, crosstalk, nuclear receptor binding domains, splicing sites, transcription factor binding sites
National Category
Biochemistry and Molecular Biology
Research subject
Translational Medicine TRIM
Identifiers
urn:nbn:se:his:diva-19687 (URN)10.1515/med-2021-0264 (DOI)000645596800001 ()33954257 (PubMedID)2-s2.0-85104533727 (Scopus ID)
Note

CC BY 4.0

© 2021 Maria Araceli Diaz Cruz et al., published by De Gruyter 2021.

Corresponding author: Maria Araceli Diaz Cruz, Research School of Health and Welfare, School of Health and Welfare, Jönköping University, Jönköping, Sweden, e-mail: Maria-Araceli.Cruz@ju.se, tel: +46-737553177

This study was financially supported by Högskolans Jubileumsfond at the University College of Skövde (Dnr HS 2015/536). Jönköping University provided with open access funding and the necessary resources to carry out this investigation.

Available from: 2021-05-06 Created: 2021-05-06 Last updated: 2022-12-21Bibliographically approved
Diaz Cruz, M. A., Karlsson, S., Szekeres, F., Faresjö, M., Lund, D. & Larsson, D. (2021). Differential expression of protein disulfide-isomerase A3 isoforms, PDIA3 and PDIA3N, in human prostate cancer cell lines representing different stages of prostate cancer. Molecular Biology Reports, 48(3), 2429-2436
Open this publication in new window or tab >>Differential expression of protein disulfide-isomerase A3 isoforms, PDIA3 and PDIA3N, in human prostate cancer cell lines representing different stages of prostate cancer
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2021 (English)In: Molecular Biology Reports, ISSN 0301-4851, E-ISSN 1573-4978, Vol. 48, no 3, p. 2429-2436Article in journal (Refereed) Published
Abstract [en]

Prostate cancer (PCa) is a highly heterogeneous and unpredictable progressive disease. Sensitivity of PCa cells to androgens play a central role in tumor aggressiveness but biomarkers with high sensitivity and specificity that follow the progression of the disease has not yet been verified. The vitamin D endocrine system and its receptors, the Vitamin D Receptor (VDR) and the Protein Disulfide-Isomerase A3 (PDIA3), are related to anti-tumoral effects as well as carcinogenesis and have therefore been suggested as potential candidates for the prevention and therapy of several cancer forms, including PCa. In this study, we evaluated the mRNA expression of VDR and PDIA3 involved in vitamin D signaling in cell lines representing different stages of PCa (PNT2, P4E6, LNCaP, DU145 and PC3). This study further aimed to evaluate vitamin D receptors and their isoforms as potential markers for clinical diagnosis of PCa. A novel transcript isoform of PDIA3 (PDIA3N) was identified and found to be expressed in all PCa cell lines analyzed. Androgen-independent cell lines showed a higher mRNA expression ratio between PDIA3N/PDIA3 contrary to androgen-dependent cell lines that showed a lower mRNA expression ratio between PDIA3N/PDIA3. The structure of PDIA3N differed from PDIA3. PDIA3N was found to be a N-truncated isoform of PDIA3 and differences in protein structure suggests an altered protein function i.e. cell location, thioredoxin activity and affinity for 1,25(OH)2D3. Collectively, PDIA3 transcript isoforms, the ratio between PDIA3N/PDIA3 and especially PDIA3N, are proposed as candidate markers for future studies with different stages of PCa progression. 

Place, publisher, year, edition, pages
Springer, 2021
Keywords
Androgen dependency, PDIA3, PDIA3N, Prostate cancer, VDR, Vitamin D
National Category
Cancer and Oncology
Research subject
Translational Medicine TRIM
Identifiers
urn:nbn:se:his:diva-19611 (URN)10.1007/s11033-021-06277-1 (DOI)000632300000004 ()33761087 (PubMedID)2-s2.0-85103162678 (Scopus ID)
Note

CC BY 4.0

Available from: 2021-04-13 Created: 2021-04-13 Last updated: 2022-12-16Bibliographically approved
Lundh, D., Hedelin, H., Jonsson, K., Gifford, M. & Larsson, D. (2013). Assessing chronic pelvic pain syndrome patients: Blood plasma factors and cortisol saliva. Scandinavian Journal of Urology, 47(6), 521-528
Open this publication in new window or tab >>Assessing chronic pelvic pain syndrome patients: Blood plasma factors and cortisol saliva
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2013 (English)In: Scandinavian Journal of Urology, ISSN 2168-1813, Vol. 47, no 6, p. 521-528Article in journal (Refereed) Published
Abstract [en]

Objective. The aim of this study was to identify changes in inflammatory molecules in the blood (plasma) of patients with chronic prostatitis/chronic pelvic syndrome (CP/CPPS) compared with controls. Altered levels indicate a systemic component by possible involvement of the prostate and/or the inner pelvic floor musculature. Material and methods. In 32 patients with CP/CPPS and 37 controls, blood plasma levels of testosterone, macrophage migration inhibitory factor (MIF), tumour necrosis factor-alpha (TNF-alpha), TNF-beta, interleukin-2 (IL-2) and IL-1 beta were measured by enzyme-linked immunosorbent assay. Cortisol in saliva samples was measured in the morning and late evening. All participants answered a questionnaire regarding their health profile. Results. Significantly higher levels of MIF (p = 0.012) were detected in patients. The testosterone level was, contrary to other studies, little lower in patients (p = 0.014; age adjusted). When controls with health issues and patients with a parallel disease were excluded, the MIF and TNF-alpha levels were higher in the patients (p = 0.007, p = 0.016, respectively) than in controls, and the testosterone was slightly lower in patients (p = 0.047). Conclusions. The findings show an immune response extending to the circulatory system, in which MIF makes a significant contribution to CP/CPPS. This study also indicates TNF-alpha as a circulatory component when excluding subjects with concomitant diseases. Both MIF and TNF-alpha have previously been highlighted for other diseases related to chronic pain and here also for CP/CPPS. These results provide further insights into the immunological basis of CP/CPPS.

Place, publisher, year, edition, pages
Informa Healthcare, 2013
National Category
Urology and Nephrology Biochemistry and Molecular Biology
Research subject
Medical sciences
Identifiers
urn:nbn:se:his:diva-8783 (URN)10.3109/21681805.2013.769460 (DOI)000328899000013 ()23394140 (PubMedID)2-s2.0-84890518365 (Scopus ID)
Available from: 2014-02-14 Created: 2014-02-14 Last updated: 2023-04-19Bibliographically approved
Lundh, D., Hedelin, H. & Larsson, D. (2013). Chronic prostatitis/chronic pelvic pain syndrome: Interplay of inflammatory mediators, "Beyond the Abstract". UroToday International Journal
Open this publication in new window or tab >>Chronic prostatitis/chronic pelvic pain syndrome: Interplay of inflammatory mediators, "Beyond the Abstract"
2013 (English)In: UroToday International Journal, ISSN 1939-4810Article in journal (Refereed) Published
Place, publisher, year, edition, pages
UroToday Inc., 2013
National Category
Urology and Nephrology
Research subject
Natural sciences
Identifiers
urn:nbn:se:his:diva-8578 (URN)
Available from: 2013-10-28 Created: 2013-10-28 Last updated: 2021-08-04Bibliographically approved
Larsson, D., Jonas, A., Bergsten, N., Ståhl, F. & Karlsson, S. (2012). Membrane Initiated Effects of1α,25-Dihydroxyvitamin D3 inProstate Cancer Cells: Effects on AP1 and CREB Mediated Transcription. In: Stevo Najman (Ed.), Current Frontiers and Perspectives in Cell Biology: (pp. 153-162). InTech
Open this publication in new window or tab >>Membrane Initiated Effects of1α,25-Dihydroxyvitamin D3 inProstate Cancer Cells: Effects on AP1 and CREB Mediated Transcription
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2012 (English)In: Current Frontiers and Perspectives in Cell Biology / [ed] Stevo Najman, InTech, 2012, p. 153-162Chapter in book (Refereed)
Place, publisher, year, edition, pages
InTech, 2012
National Category
Biological Sciences
Research subject
Natural sciences
Identifiers
urn:nbn:se:his:diva-6484 (URN)10.5772/32908 (DOI)978-953-51-0544-2 (ISBN)
Available from: 2012-10-09 Created: 2012-10-09 Last updated: 2023-05-12Bibliographically approved
Berggren, E., Sidenvall, B. & Larsson, D. (2011). Subarachnoid haemorrhage has long-term effects on social life. British Journal of Neuroscience Nursing, 7(1), 429-435
Open this publication in new window or tab >>Subarachnoid haemorrhage has long-term effects on social life
2011 (English)In: British Journal of Neuroscience Nursing, ISSN 1747-0307, E-ISSN 2052-2800, Vol. 7, no 1, p. 429-435Article in journal (Refereed) Published
Abstract [en]

Aim: The aim of this study was to describe memory after a subarachnoid haemorrhage (SAH) from the perspective of relatives and patients in two cohorts and also to evaluate the application of relatives' statements as a tool in nursing care and rehabilitation, in order to support the patient. Background: Cognitive sequelae due to SAH are a large disability and may influence the adjustment to daily life. Supporting patients and relatives requires knowledge concerning the patients' memory both from the perspective of patients and relatives. Method: Eleven relatives and 11 patients (Cohort 1), 11 years after the onset of an SAH and 15 relatives and 15 patients (Cohort 2) 6 years after the onset of an SAH, participated in the study. Interview questions and memory tests were used to collect data. Findings: Problems with memory, including meta-memory problems regarding relatives' statements, were common. Relatives and patients stated patients' menory in a similar manner. However, patients' statements concerning their memory corresponded in higher degree with memory test results, in comparison with relatives' statements. Conclusions: Relatives' and patients' statements are useful as tools in nursing care and rehabilitation. However, from results showing meta-memory problems and that patients' statements concerning their memory corresponded better with memory test results (in comparison with relatives' statements), it is vital to offer patients memory tests in order to prevent complications in mutual family relationships.

Place, publisher, year, edition, pages
MA Healthcare Ltd., 2011
Keywords
Subarachnoid haemorrhage, SAH, stroke, memory, memory test, interview questions
National Category
Nursing Neurology
Research subject
Medical sciences
Identifiers
urn:nbn:se:his:diva-4609 (URN)10.12968/bjnn.2011.7.1.429 (DOI)
Available from: 2011-01-21 Created: 2011-01-21 Last updated: 2023-11-09Bibliographically approved
Lundh, D., Larsson, D., Nahar, N. & Mandal, A. (2010). Arsenic accumulation in plants - Outlining strategies for developing improved variety of crops for avoiding arsenic toxicity in foods. Journal of biological systems, 18(1), 223-241
Open this publication in new window or tab >>Arsenic accumulation in plants - Outlining strategies for developing improved variety of crops for avoiding arsenic toxicity in foods
2010 (English)In: Journal of biological systems, ISSN 0218-3390, Vol. 18, no 1, p. 223-241Article in journal (Refereed) Published
Abstract [en]

Contamination of food with arsenics is a potential health risk for both humans and animals in many regions of the world, especially in Asia. Arsenics can be accumulated in humans, animals and plants for a longer period and a long-term exposure of humans to arsenics results in severe damage of kidney, lever, heart etc. and many other vascular diseases. Arsenic contamination in human may also lead to development of cancer. In this paper we report our results on data mining approach (an in silico analysis based on searching of the existing genomic databases) for identification and characterization of genes that might be responsible for uptake, accumulation or metabolism of arsenics. For these in silico analyses we have involved the model plant Arabidopsis thaliana in our investigation. By employing a system biology model (a kinetic model) we have studied the molecular mechanisms of these processes in this plant. This model contains equations for uptake, metabolism and sequestration of different types of arsenic; As(V), As(III), MMAA and DMAA. The model was then implemented in the software XPP. The model was also validated against the data existing in the literatures. Based on the results of these in silico studies we have developed some strategies that can be used for reducing arsenic contents in different parts of the plant. Data mining experiments resulted in identification of two candidate genes (ACR2, arsenate reductase 2 and PCS1, phytochelatin synthase 1) that are involved either in uptake, transport or cellular localization of arsenic in A. thaliana. However, our system biology model revealed that by increasing the level of arsenate reductase together with an increased rate of arsenite sequestration in the vacuoles (by involving an arsenite efflux pump MRP1/2), it is possible to reduce the amount of arsenics in the shoots of A. thaliana to 11–12%.

Place, publisher, year, edition, pages
World Scientific Publishing Co., 2010
Keywords
Arsenic Toxicity; Arsenic Accumulation; Kinetic Model; Strategy for Arsenics
National Category
Natural Sciences
Research subject
Natural sciences
Identifiers
urn:nbn:se:his:diva-4325 (URN)10.1142/S0218339010003214 (DOI)000275713700011 ()2-s2.0-77951694527 (Scopus ID)
Available from: 2010-08-25 Created: 2010-08-25 Last updated: 2020-01-29Bibliographically approved
Berggren, E., Sidenvall, B. & Larsson, D. (2010). Memory ability after subarachnoid haemorrhage: Relatives' and patients' statements in relation to test results. British Journal of Neuroscience Nursing, 6(8), 383-391
Open this publication in new window or tab >>Memory ability after subarachnoid haemorrhage: Relatives' and patients' statements in relation to test results
2010 (English)In: British Journal of Neuroscience Nursing, ISSN 1747-0307, E-ISSN 2052-2800, Vol. 6, no 8, p. 383-391Article in journal (Refereed) Published
Abstract [en]

Aim: The aim of this study was to describe memory after a subarachnoid haemorrhage (SAH) from the perspective of relatives and patients in two cohorts and also to evaluate the application of relatives' statements as a tool in nursing care and rehabilitation, in order to support the patient.

Background: Cognitive sequelae due to SAH are a large disability and may influence the adjustment to daily life. Supporting patients and relatives requires knowledge concerning the patients' memory both from the perspective of patients and relatives.

Method: Eleven relatives and 11 patients (Cohort 1), 11 years after the onset of a SAH and 15 relatives and 15 patients (Cohort 2) 6 years after the onset of a SAH, participated in the study. Interview questions and memory tests were used to collect data.

Findings: Problems with memory, including meta-memory problems regarding relatives' statements, were common. Relatives and patients stated patients' memory in a similar manner. However, patients' statements concerning their memory corresponded in higher degree with memory test results, in comparison with relatives' statements.

Conclusions: Relatives' and patients' statements are useful as tools in nursing care and rehabilitation. However, from results showing meta-memory problems and that patients' statements concerning their memory corresponded better with memory test results (in comparison with relatives' statements), it is vital to offer patients memory tests in order to prevent complications in mutual family relationships.

Place, publisher, year, edition, pages
MA Healthcare Ltd., 2010
National Category
Nursing Neurology
Research subject
Medical sciences
Identifiers
urn:nbn:se:his:diva-23345 (URN)10.12968/bjnn.2010.6.8.383 (DOI)
Available from: 2023-11-08 Created: 2023-11-08 Last updated: 2023-11-09Bibliographically approved
Sogaard, P., Szekeres, F., Garcia-Roves, P. M., Larsson, D., Chibalin, A. V. & Zierath, J. R. (2010). Spatial Insulin Signalling in Isolated Skeletal Muscle Preparations. Journal of Cellular Biochemistry, 109(5), 943-949
Open this publication in new window or tab >>Spatial Insulin Signalling in Isolated Skeletal Muscle Preparations
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2010 (English)In: Journal of Cellular Biochemistry, ISSN 0730-2312, E-ISSN 1097-4644, Vol. 109, no 5, p. 943-949Article in journal (Refereed) Published
Abstract [en]

During in vitro incubation in the absence or presence of insulin, glycogen depletion occurs in the inner core of the muscle specimen, concomitant with increased staining of hypoxia-induced-factor-1-alpha and caspase-3, markers of hypoxia and apoptosis, respectively. The aim of this study was to determine whether insulin is able to diffuse across the entire muscle specimen in sufficient amounts to activate signalling cascades to promote glucose uptake and glycogenesis within isolated mouse skeletal muscle. Phosphoprotein multiplex assay on lysates from muscle preparation was performed to detect phosphorylation of insulin-receptor on Tyr1146, Akt on Ser473 and glycogen-synthases-kinase-3 on Ser21/Ser9. To address the spatial resolution of insulin signalling, immunohistochemistry studies on cryosections were performed. Our results provide evidence to suggest that during the in vitro incubation, insulin sufficiently diffuses into the centre of tubular mouse muscles to promote phosphorylation of these signalling events. Interestingly, increased insulin signalling was observed in the core of the incubated muscle specimens, correlating with the location of oxidative fibres. In conclusion, insulin action was not restricted due to insufficient diffusion of the hormone during in vitro incubation in either extensor digitorum longus or soleus muscles from mouse under the specific experimental settings employed in this study. Hence, we suggest that the glycogen depleted core as earlier observed is not due to insufficient insulin action.

Place, publisher, year, edition, pages
Wiley-Liss, Inc., 2010
Keywords
In Vitro Incubation, Immunohistochemistry, Extensor Digitorum Longus, Soleus, Spatial
National Category
Natural Sciences
Research subject
Natural sciences
Identifiers
urn:nbn:se:his:diva-4330 (URN)10.1002/jcb.22470 (DOI)000276418900013 ()20069552 (PubMedID)2-s2.0-77950407958 (Scopus ID)
Available from: 2010-08-26 Created: 2010-08-26 Last updated: 2020-01-28Bibliographically approved
Karlsson, S., Olausson, J., Lundh, D., Sögård, P., Mandal, A., Holmström, K.-O., . . . Larsson, D. (2010). Vitamin D and prostate cancer: The role of membrane initiated signaling pathways in prostate cancer progression. Journal of Steroid Biochemistry and Molecular Biology, 121(1-2), 413-416
Open this publication in new window or tab >>Vitamin D and prostate cancer: The role of membrane initiated signaling pathways in prostate cancer progression
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2010 (English)In: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 121, no 1-2, p. 413-416Article in journal (Refereed) Published
Abstract [en]

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has been demonstrated to mediate both genomic and non-genomic responses in prostate cancer (CaP) cells. Here, we give an overview of membrane initiated 1,25(OH)2D3 signaling in prostate cancer cell progression. The presence of PDIA3 was investigated and homologous modeling of the putative PDIA3 receptor complex was conducted. Furthermore, the cellular distribution of nVDR was analyzed. We could show that both nVDR and PDIA3 are expressed in the prostate cancer cell lines investigated. The homologous modeling of PDIA3 showed that the receptor complex exists in a trimer formation, which suggests for allosteric activity. Our findings support previous reports and suggest that 1,25(OH)2D3 is an important therapeutic agent in inhibiting prostate cancer progression. Furthermore, our data show that 1,25(OH)2D3 regulate prostate cell biology via multiple pathways and targeting specific pathways for 1,25(OH)2D3 might provide more effective therapies compared to the vitamin D therapies currently clinically tested.

Place, publisher, year, edition, pages
Elsevier, 2010
Keywords
1, 25(OH)2D3, Prostate cancer, Membrane receptors, PDIA3, nVDR, Receptor modeling
National Category
Natural Sciences
Research subject
Natural sciences
Identifiers
urn:nbn:se:his:diva-4528 (URN)10.1016/j.jsbmb.2010.03.083 (DOI)000280600200091 ()20398754 (PubMedID)2-s2.0-77954760891 (Scopus ID)
Available from: 2011-01-03 Created: 2011-01-03 Last updated: 2020-01-29Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-4724-0269

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