| 1. |
- Kalikstad, Betty, et al.
(författare)
-
Gene expression profiles in preterm infants on continuous long-term oxygen therapy suggest reduced oxidative stress-dependent signaling during hypoxia
- 2017
-
Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 15:4, s. 1513-1526
-
Tidskriftsartikel (refereegranskat)abstract
- Preterm infants are susceptible to neonatal inflammatory/ infective diseases requiring drug therapy. The present study hypothesized that mRNA expression in the blood may be modulated by signaling pathways during treatment. The current study aimed to explore changes in global gene expression in the blood from preterm infants with the objective of identifying patterns or pathways of potential relevance to drug therapy. The infants involved were selected based on maternal criteria indicating increased risk for therapeutic intervention. Global mRNA expression was measured in 107 longitudinal whole blood samples using Affymetrix Human-Genome-U133 Plus 2.0-arrays; samples were obtained from 20 preterm infants. Unsupervised clustering revealed a distinct homogeneous gene expression pattern in 13 samples derived from seven infants undergoing continuous oxygen therapy. At these sampling times, all but one of the seven infants exhibited severe drops in peripheral capillary saturation levels below 60%. The infants were reoxygenated with 100% inspired oxygen concentration. The other samples ( n= 94) represented the infants from the cohort at time points when they did not undergo continuous oxygen therapy. Comparing these two sets of samples identified a distinct gene expression pattern of 5,986 significantly differentially expressed genes, of which 5,167 genes exhibited reduced expression levels during transient hypoxia. This expression pattern was reversed when the infants became stable, i. e., when they were not continuously oxygenated and had no events of hypoxia. To identify signaling pathways involved in gene regulation, the Database for Annotation, Visualization and Integrated Discovery online tool was used. Mitogen-activated protein kinases, which are normally induced by oxidative stress, exhibited reduced gene expression during hypoxia. In addition, nuclear factor erythroid 2-related factor 2-antioxidant response element target genes involved in oxidative stress protection were also expressed at lower levels, suggesting reduced transcription of this pathway. The findings of the present study suggest that oxidative stress-dependent signaling is reduced during hypoxia. Understanding the molecular response in preterm infants during continuous oxygenation may aid in refining therapeutic strategies for oxygen therapy.
|
|
| 2. |
- Palsdottir, Vilborg, 1979, et al.
(författare)
-
Prenatal essential fatty acid deficiency in mice results in long-term gender-specific effects on body weight and glucose metabolism
- 2011
-
Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 4:4, s. 731-737
-
Tidskriftsartikel (refereegranskat)abstract
- Essential fatty acids are important for normal growth and development in early life. However, the long-term effects of prenatal essential fatty acid deficiency (EFAD) on the adult metabolism remain to be determined. The aim of this study was to investigate the effects of an EFAD diet given to mice during late gestation on body weight and body composition, and metabolism in the adult offspring. Pregnant dams were given an EFAD or a control diet during the last 10 days of gestation. After delivery, all mice were fed normal chow and the body weight of the offspring was measured weekly. Furthermore, food intake, energy expenditure and intraperitoneal glucose tolera-nce were analysed in the adult offspring in addition to body composition (analysed by dual-energy X-ray absorptiometry), plasma levels of leptin, triglycerides and cholesterol. The body weight was lower in the EFAD offspring as compared to the controls during the first 4 weeks of age, and remained lower in the females throughout the study. Lean body mass and plasma leptin levels were also lower in the female EFAD offspring as compared to the controls. Male EFAD offspring were found to have higher fasting glucose and insulin levels as well as higher insulin levels during the glucose tolerance test compared to the controls. However, no differences were found in blood lipids, food intake or energy expenditure between EFAD and control mice of either gender. These results demonstrate that an EFAD diet given during the last 10 days of gestation results in long-term gender-specific effects on body weight and insulin sensitivity in the adult offspring.
|
|
| 3. |
- Zhang, Yi, et al.
(författare)
-
Elemene inhibits the migration and invasion of 4T1 murine breast cancer cells via heparanase
- 2017
-
Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 16:1, s. 794-800
-
Tidskriftsartikel (refereegranskat)abstract
- Elemene (ELE), a natural plant drug extracted from Curcumae Rhizoma, has been widely used for cancer treatment in China for more than 20 years. Although it is reported to be a broad-spectrum anticancer drug, the mechanism underlying the action of ELE in the treatment of breast cancer remains to be fully elucidated. Heparanase, a mammalian endo-D-glucuronidase, is involved in degradation of the extracellular matrix (ECM), and thus promotes tumor progression and metastasis. The downregulation of heparanase can effectively reduce tumor malignant behaviors. In the present study, the inhibitory effects of ELE were evaluated in breast cancer cells using a Cell Counting kit 8 assay. The migratory and invasive capabilities of cancer cells were investigated using a wound healing assay, real-time cell analysis and a Transwell assay. In addition, western blot analysis was used to assess alterations in the expression levels of key proteins. The present results confirmed the antiproliferative and antimetastatic effects of ELE, using low-molecular weight heparin (LMWH) as a positive control. In addition, ELE was demonstrated to downregulate the expression of heparanase, and decrease the phosphorylation of extracellular signal-regulated kinase and AKT. These findings suggested that ELE may be a promising agent targeting heparanase in the treatment of breast cancer.
|
|
| 4. |
- Alehagen, Urban, 1951-, et al.
(författare)
-
Genetic variance and plasma concentration of CD93 is associated with cardiovascular mortality : Results from a 6.7-year follow-up of a healthy community-living elderly population
- 2020
-
Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 22:6, s. 4629-4636
-
Tidskriftsartikel (refereegranskat)abstract
- Inflammation is one of the fundamental processes in numerous diseases. Cluster of differentiation (CD) 93, a glycoprotein, has been reported to be associated with a number of these diseases. There are reports indicating that a high plasma level of CD93 is associated with adverse events in ischaemic heart disease. Additionally, there are reports indicating different cardiovascular risks between different single nucleotide polymorphisms (SNPs) of CD93. Therefore, the present study aimed to determine whether the plasma concentration of CD93 and polymorphism of rs2749812 in CD93 were associated with clinical conditions and mortality in an elderly population. In 470 healthy elderly community-living individuals a novel clinical examination involving echocardiography and blood sampling was performed. The population was followed for 6.7 years. Plasma levels of CD93 and SNP analyses of rs2749812 of CD93 using PCR methodology were used. During the follow-up period, 106 (22.6%) all-cause and 61 (13.0%) cardiovascular deaths were registered. Those with the highest plasma concentration had markedly higher all-cause mortality. Evaluating the A/A, A/G and G/G genotypes, the G/G group exhibited significantly higher cardiovascular mortality (P=0.026), and an almost two-fold increased risk in a multivariate Cox regression model compared with the A/G genotype. Evaluation of subgroups with respect to sex, diabetes and hypertension revealed markedly increased cardiovascular risk in the G/G genotype in all subgroups. All results persisted in the multiple models used. In the present study, the glycoprotein CD93 was demonstrated to have prognostic cardiovascular information, with increased risk for those with a high plasma concentration. Furthermore, the G/G genotype of rs2749812 of CD93 has a significantly higher cardiovascular risk, as demonstrated here, and could therefore be regarded as a possible cardiovascular risk biomarker that might in the future be used to offer optimised cardiovascular patient handling. However, this was a small study, and more research is required.
|
|
| 5. |
- Fragkiadaki, Persefoni, et al.
(författare)
-
Telomerase inhibitors and activators in aging and cancer : A systematic review
- 2022
-
Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 25:5
-
Forskningsöversikt (refereegranskat)abstract
- The main aim of the present systematic review was to summarize the most frequently used telomerase regulators with an impact on aging and cancer that are referred to in in vitro and in vivo studies. For this purpose, a systematic review of the available literature on telomerase regulators referred to in articles from PubMed and Scopus libraries published from 2002 to 2021 and in accordance with PRISMA 2020 criteria, was conducted. Articles were included if they met the following criteria: They referred to telomerase modulators in aging and in cancer and were in vitro and/or in vivo studies, while studies that did not provide sufficient data or studies not written in English were excluded. In the present systematic review, 54 publications were included, of which 29 were full-text published studies, 11 were full-text reviews, 10 structure-based design studies and 4 abstracts are reported in this review. Telomerase regulators were then categorized as synthetic direct telomerase inhibitors, synthetic indirect telomerase inhibitors, synthetic telomerase activators, natural direct telomerase activators, natural telomerase inhibitors and natural indirect telomerase activators, according to their origin and their activity. On the whole, as demonstrated herein, telomerase regulators appear to be promising treatment agents in various age-related diseases. However, further in vivo and in vitro studies need to be performed in order to clarify the potentiality of telomerase as a therapeutic target.
|
|
| 6. |
- Lundmark, Fanny, et al.
(författare)
-
Reduction of renal activity retention of radiolabeled albumin binding domain-derived affinity proteins using a non-residualizing label strategy compared with a cleavable glycine-leucine-glycine-lysine-linker
- 2024
-
Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 29:2
-
Tidskriftsartikel (refereegranskat)abstract
- The feasibility of targeted imaging and therapy using radiolabeled albumin-binding domain-derived affinity proteins (ADAPTs) has been demonstrated. However, high renal uptake of radioactivity limits the maximum tolerated dose. Successful reduction of renal retention of radiolabeled Fab fragments has been demonstrated by incorporating a cleavable linker between the targeting agent and the radiometal chelator. The present study investigated if the introduction of a glycine-leucine-glycine-lysine (GLGK)-linker would reduce the kidney uptake of radiolabeled ADAPT6 and also compared it with the non-residualizing [125I]I-[(4-hydroxyphenyl)ethyl]maleimide ([125I]I-HPEM) labeling strategy. GLGK was site-specifically coupled to human epidermal growth factor receptor 2 (HER2)-targeting ADAPT6. Conjugates without the cleavable linker were used as controls and all constructs were labeled with lutetium-177 (177Lu). [125I]I-HPEM was coupled to ADAPT6 at the C-terminus. Biodistribution of all constructs was evaluated in NMRI mice 4 h after injection. Specific binding to HER2-expressing cells in vitro was demonstrated for all constructs. No significant difference in kidney uptake was observed between the [177Lu]Lu-2,2 ',2",2"'-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid-GLGK-conjugates and the controls. The renal activity of [125I]I-HPEM-ADAPT6 was significantly lower compared with all other constructs. In conclusion, the incorporation of the cleavable GLGK-linker did not result in lower renal retention. Therefore, the present study emphasized that, in order to achieve a reduction of renal retention, alternative molecular design strategies may be required for different targeting agents.
|
|
| 7. |
- Sjölander, Annica, 1969, et al.
(författare)
-
Alzheimer's disease: No effect of the CDK5 gene on CSF biomarkers, neuropathology or disease risk
- 2009
-
Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-3004 .- 1791-2997. ; 2:6, s. 989-992
-
Tidskriftsartikel (refereegranskat)abstract
- Cyclin-dependent kinase 5 (cdk5) has been identified as one of the kinases that phosphorylates tau at several Alzheimer's disease (AD)-associated sites. Cdk5 is predominantly expressed in neurons, and has higher activity in AD brains than in non-demented brains. To investigate the effect of the CDK5 gene on AD, we analyzed an SNP of the CDK5 gene (rs2069456) in 347 patients with AD and in 157 controls. CDK5 genetic data was investigated in subgroups in relation to biochemical and neuropathological markers for AD. We found no significant differences in genotype or allele distributions between AD patients and controls. None of the CDK5 gene variants influenced biomarkers for AD.
|
|
| 8. |
- Zhu, Zhechen, et al.
(författare)
-
Association between the ABCC11 gene polymorphism and the expression of apolipoprotein D by the apocrine glands in axillary osmidrosis.
- 2015
-
Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-3004 .- 1791-2997. ; 11:6, s. 4463-4467
-
Tidskriftsartikel (refereegranskat)abstract
- It has been suggested that the adenosine triphosphate‑binding cassette sub‑family C member 11 (ABCC11) gene polymorphism and apolipoprotein D (ApoD), an odor precursor carrier, may be important in the formation of axillary odor. To date, few studies have examined the potential correlation between these two factors. The present study aimed to investigate the association between a 538 G>A single‑nucleotide polymorphism (SNP) of the ABCC11 gene and the mRNA expression levels of ApoD in the apocrine gland of patients with osmidrosis. The 538 G>A polymorphism genotypes of 33 patients with a clinical diagnosis of osmidrosis were analyzed by polymerase chain reaction (PCR) and a base‑quenched probe method, and they were divided into two groups according to the results. The G allele functions as a dominant gene; therefore, patients with the GG or GA genotype were allocated to Group I (n=28) and patients with the AA genotype to Group II (n=5). The mRNA expression levels of ApoD in the apocrine glands were determined by reverse transcription‑PCR. The results indicated that the mRNA expression levels of ApoD were significantly higher in the apocrine glands of patients in Group I compared with those in Group II (P<0.01). In conclusion, the results indicated that the ABCC11 gene SNP of the 538 G>A allele was associated with a downregulation of the mRNA expression of ApoD in the apocrine glands, which may indicate a role for the ABCC11 gene in the mediation of osmidrosis by enhancing the transition of odor precursors via the ApoD pathway.
|
|
| 9. |
- Zhu, Ziqiang, et al.
(författare)
-
Integrative microRNA and mRNA expression profiling in acute aristolochic acid nephropathy in mice
- 2020
-
Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 22:4, s. 3367-3377
-
Tidskriftsartikel (refereegranskat)abstract
- In acute aristolochic acid nephropathy (AAN), aristolochic acid (AA) induces renal injury and tubulointerstitial fibrosis. However, the roles of microRNAs (miRNAs/miRs) and mRNAs involved in AAN are not clearly understood. The aim of the present study was to examine AA-induced genome-wide differentially expressed (DE) miRNAs and DE mRNAs using deep sequencing in mouse kidneys, and to analyze their regulatory networks. In the present self-controlled study, mice were treated with 5 mg/kg/day AA for 5 days, following unilateral nephrectomy. AA-induced renal injury and tubulointerstitial fibrosis were detected using hematoxylin and eosin staining and Masson's trichrome staining in the mouse kidneys. A total of 82 DE miRNAs and 4,605 DE mRNAs were identified between the AA-treated group and the self-control group. Of these DE miRNAs and mRNAs, some were validated using reverse transcription-quantitative PCR. Expression levels of the profibrotic miR-21, miR-433 and miR-132 families were significantly increased, whereas expression levels of the anti-fibrotic miR-122-5p and let-7a-1-3p were significantly decreased. Functions and signaling pathways associated with the DE miRNAs and mRNAs were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG). A total of 767 DE pairs (in opposing directions) of miRNAs and their mRNA targets were identified. Among these, regulatory networks of miRNAs and mRNAs were analyzed using KEGG to identify enriched signaling pathways and extracellular matrix-associated pathways. In conclusion, the present study identified genome-wide DE miRNAs and mRNAs in the kidneys of AA-treated mice, as well as their regulatory pairs and signaling networks. The present results may improve the understanding of the role of DE miRNAs and their mRNA targets in the pathophysiology of acute AAN.
|
|
| 10. |
- Erlandson, Anna, et al.
(författare)
-
Epigenetic mutations in CDKN2A in western Swedish families with hereditary malignant melanoma
- 2008
-
Ingår i: Molecular Medicine Reports. - Athens, Greece : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 1:1, s. 89-91
-
Tidskriftsartikel (refereegranskat)abstract
- This study aimed to identify the molecular genetic variations associated with an increased risk of hereditary malignant melanoma (HMM) in the western Swedish population. In 68 families with increased hereditary susceptibility to malignant melanoma, we previously reported a low frequency of alterations in the CDKN2A gene, which is regarded as the major melanoma predisposition gene. Among these alterations, we identified a novel mutation in 3 families (Asp108Tyr). In the present study, we focused on the possible role of heritable epimutations as a cause of the silencing of the CDKN2A gene. We used two different technical approaches to detect changes in CpG methylation in the promoter region of the CDKN2A gene; methylation-specific PCR (MSP) analysis of bisulfite-converted DNA and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). From families who tested negative for germ-line CDKN2A mutations, 64 unrelated patients with hereditary melanoma were included in the study. We showed a consistent lack of hypermethylation in the promoter region of CDKN2A in patients with HMM in our western Swedish population. A putative germ-line methylation of the CDKN2A, if any, is therefore likely to be a rare event in hereditary melanoma. This study demonstrates that there are probably additional and as yet unknown genetic factors present in western Swedish HMM families.
|
|
