| 1. |
- Alehagen, Urban, 1951-, et al.
(författare)
-
Increased mortality in the A/A genotype of the SNP rs28372698 of interleukin 32
- 2021
-
Ingår i: Experimental and Therapeutic Medicine. - : SPANDIDOS PUBL LTD. - 1792-0981 .- 1792-1015. ; 21:2
-
Tidskriftsartikel (refereegranskat)abstract
- One of the major causes of mortality in the western hemisphere is cardiovascular disease. Therefore, a variety of markers to identify those at risk are required. Interleukin-32 (IL-32) is a cytokine that is associated with inflammation. The aim of the current study was to investigate variations in single nucleotide polymorphisms (SNPs) of IL-32 and plasma expression, and their associations with mortality. A population of 486 elderly community-living persons were evaluated. The participants were followed for 7.1 years and underwent a clinical examination and blood sampling. SNP analyses of IL-32 rs28372698 using allelic discrimination and plasma measurement of IL-32, using ELISA, were performed. During the follow-up period, 140 (28.8%) all-cause and 87 (17.9%) cardiovascular deaths were registered. No significant difference between mortality and plasma concentration of IL-32 was observed. The A/A genotype group exhibited significantly higher all-cause mortality (P=0.036), and an almost two-fold increased risk in a multivariate Cox regression model for all-cause and cardiovascular mortality. A highly significant difference in all-cause and cardiovascular mortality between the A/A and the T/T groups was demonstrated (P=0.015 resp. P=0.014). In the present study, the cytokine IL-32 was demonstrated to have prognostic information, with an increased risk of all-cause and cardiovascular mortality for those with the A/A genotype rs28372698 of IL-32. The A/A genotype could therefore be regarded as a possible biomarker for mortality risk that may be used to offer optimized cardiovascular patient handling in the future. However, the present study sample was small, and the results should be regarded as hypothesis-generating.
|
|
| 2. |
- Bartik, Zsuzsa, et al.
(författare)
-
A genome-wide scan to locate regions associated with familial vesicoureteral reflux
- 2022
-
Ingår i: Experimental and Therapeutic Medicine. - : Spandidos Publications. - 1792-0981 .- 1792-1015. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- Vesicoureteral reflux (VUR) is a congenital malformation carrying a high risk of recurrent urinary tract infections (UTI) and, at worst, chronic renal failure. Familial clustering implies a genetic etiology, but studies during the past few decades have demonstrated a causal gene variant in <10% of patients with VUR. The aim of the present study was to search for fully or partially shared ancestral haplotypes in 14 families from south-western Sweden with at least three affected members. High-density single nucleotide polymorphism microarray was used for genotyping prior to analysis with a compatibility matching method developed in-house, and the analysis of copy number variations (CNV). No single unique haplotype was revealed to be shared by the families, thereby excluding a common ancestry and founder mutations as a probable cause of VUR. After evaluation of haplotypes shared by subsets of families, a haplotype shared by nine families was found to be of particular interest. This haplotype, located at chromosomal region 4q21.21, harbours two tentative candidate genes (bone morphogenetic protein 3 and fibroblast growth factor 5), both expressed in metanephros and with known functions during nephrogenesis. As to CNV, only one family had a specific CNV shared by all affected members. This was a focal deletion at 5q31.1 including follistatin-like 4, a gene without a previous known connection to VUR. These data demonstrated the genetic heterogeneity of VUR and indicated that an interaction of environmental and genetic factors, including non-coding and epigenetic regulators, all contribute to the complexity of VUR.
|
|
| 3. |
- Chen, Yulong, et al.
(författare)
-
Endothelium-dependent and-independent relaxation induced by resveratrol in rat superior mesenteric arteries
- 2016
-
Ingår i: Experimental and Therapeutic Medicine. - : Spandidos Publications. - 1792-0981 .- 1792-1015. ; 12:4, s. 2241-2246
-
Tidskriftsartikel (refereegranskat)abstract
- Resveratrol (Res) is a specific agonist of sirtuin 1, and has many cardioprotective effects. Although Res is able to relax various vascular beds, its pharmacological properties in rat superior mesenteric arteries and the underlying mechanism are not well clarified. The aim of present study was to investigate the vasorelaxant effects of Res on rat superior mesenteric arteries and the mechanisms involved. The isometric tension of rat superior mesenteric arterial rings was recorded in vitro using myography. It was found that Res concentration-dependently relaxed endothelium-intact superior mesenteric artery rings pre-contracted by phenylephrine hydrochloride (Emax, 97.66±0.79%; pD2, 4.30±0.14) or KCl (Emax, 101.3±0.6%; pD2, 4.12±0.03). The vasorelaxant effect of Res on the superior mesenteric artery rings was partially endothelium-dependent. NG-nitro-L-arginine methyl ester (100 µM) significantly inhibited the Res-induced vasorelaxant effect. However, 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (10 µM) and indomethacin (5 µM) each had no effect on the Res-induced vasorelaxation. In artery rings without endothelium, the vasorelaxation induced by Res was attenuated by 4-aminopyridine (100 µM) and glibenclamide (10 µM). However, barium chloride dehydrate (10 µM) and tetraethylammonium chloride (1 mM) did not affect the vasorelaxation induced by Res. Moreover, Res also inhibited the contraction induced by an increase in external calcium concentration in Ca2+-free medium plus KCl (60 mM). These results suggest that Res induces relaxation in superior mesenteric arterial rings through an endothelium-dependent pathway, involving nitric oxide release, and also through an endothelium-independent pathway, with opening of voltage-dependent K+ channels and ATP-sensitive K+ channels and blockade of extracellular Ca2+ influx.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Jellvert, Åsa, et al.
(författare)
-
Effective oral combination metronomic chemotherapy with low toxicity for the management of castration-resistant prostate cancer.
- 2011
-
Ingår i: Experimental and therapeutic medicine. - : Spandidos Publications. - 1792-1015 .- 1792-0981. ; 2:4, s. 579-584
-
Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer (PC) was previously believed to be a chemoresistant disease. In recent years taxane-based chemotherapy has been shown to prolong survival in patients with castration-resistant prostate cancer (CRPC). It remains to be shown, however, which type of chemotherapy provides the most beneficial effect with the least amount of side effects. Seventeen patients with chemonaive CRPC were enrolled in a pilot study evaluating an orally administered chemo-hormonal treatment regimen using a weekly sequential combination called KEES; consisting of ketoconazole in combination with cyclophosphamide or etoposide in combination with estramustine administered on alternate weeks. Prednisone was administered throughout the treatment period. Prostate-specific antigen (PSA) response and acute and chronic toxicities were evaluated. Seventeen patients with CRPC were treated; eleven patients demonstrated a median reduction in PSA of 87% (range 26-99%). Ten (59%) patients responded with a decrease in PSA >50%. Thrombocytopenia and anaemia were the most common side effects. One study fatality was reported, however, it was unclear whether this was treatment related. In conclusion, KEES may be a promising option for patients with CRPC, resulting in a clear reduction in PSA with limited toxicity. Further clinical evaluation of this metronomic chemohormonal combination is underway.
|
|
| 8. |
- Kantere, Despoina, et al.
(författare)
-
Exploring reflectance confocal microscopy as a non-invasive diagnostic tool for genital lichen sclerosus.
- 2022
-
Ingår i: Experimental and therapeutic medicine. - : Spandidos Publications. - 1792-0981 .- 1792-1015. ; 23:6
-
Tidskriftsartikel (refereegranskat)abstract
- The diagnosis of genital lichen sclerosus (LS) is often confirmed by obtaining a skin biopsy, which can lead to unwanted complications and is uncomfortable in the sensitive genital area. Thus, there is a need of finding novel, non-invasive techniques that can rapidly and accurately diagnose LS. The present study investigated the potential for reflectance confocal microscopy (RCM) to diagnose LS compared with healthy penile skin and other common penile skin disorders in males. A total of 30 male patients, including patients with LS, nonspecific balanoposthitis, plasma cell balanitis and psoriasis, and healthy individuals were included and were subject to non-invasive RCM investigation. Prominent fiber-like structures, representing hyaline sclerosis, were observed in the RCM images for almost half of the patients. Differences between healthy penile skin and LS were confirmed by identifying the edged papillae on healthy skin and their absence or obscureness in patients with LS. Notably, RCM could detect the atypical honeycomb pattern referring to dysplasia in 1 patient with LS with penile intraepithelial neoplasia. In conclusion, the present study demonstrated that RCM can detect sclerosis in penile LS. RCM can potentially become a valuable tool for monitoring patients with LS for dysplasia providing a useful non-invasive diagnostic tool for genital disorders.
|
|
| 9. |
- Lin, Zhaowei, et al.
(författare)
-
Effects of BMP2 and VEGF165 on the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells.
- 2014
-
Ingår i: Experimental and Therapeutic Medicine. - : Spandidos Publications. - 1792-1015 .- 1792-0981. ; 7:3, s. 625-629
-
Tidskriftsartikel (refereegranskat)abstract
- Bone marrow-derived mesenchymal stem cells (MSCs) are dominant seed cell sources for bone regeneration. Bone morphogenetic proteins (BMPs) initiate cartilage and bone formation in a sequential cascade. Vascular endothelial growth factor (VEGF) is an essential coordinator of extracellular matrix remodeling, angiogenesis and bone formation. In the present study, the effects of the vascular endothelial growth factor 165 (VEGF165) and bone morphogenetic protein 2 (BMP2) genes on bone regeneration were investigated by the lentivirus-mediated cotransfection of the two genes into rat bone marrow-derived MSCs. The successful co-expression of the two genes in the MSCs was confirmed using quantitative polymerase chain reaction (qPCR) and western blot analysis. The results of alizarin red and alkaline phosphatase (ALP) staining at 14 days subsequent to transfection showed that the area of staining in cells transfected with BMP2 alone was higher than that in cells transfected with BMP2 and VEGF165 or untransfected control cells, while the BMP2 + VEGF165 group showed significantly more staining than the untransfected control. This indicated that BMP2 alone exhibited a stronger effect in bone regeneration than BMP2 in combination with VEGF165. Similarly, in inducing culture medium, the ALP activity of the BMP2 + VEGF165 group was notably suppressed compared with that of the BMP2 group. The overexpression of VEGF165 inhibited BMP2-induced MSC differentiation and osteogenesis in vitro. Whether or not local VEGF gene therapy is likely to affect bone regeneration in vivo requires further investigation.
|
|
| 10. |
|
|
| 11. |
- Malmberg, Jennie, et al.
(författare)
-
Imaging agents for in vivo molecular profiling of disseminated prostate cancer : Cellular processing of [In-111]-labeled CHX-A "DTPA-trastuzumab and anti-HER2 ABY-025 Affibody in prostate cancer cell lines
- 2011
-
Ingår i: Experimental and Therapeutic Medicine. - : Spandidos Publications. - 1792-0981 .- 1792-1015. ; 2:3, s. 523-528
-
Tidskriftsartikel (refereegranskat)abstract
- The treatment of disseminated prostate cancer remains a great challenge in current oncology practice. The proliferation of prostate cancer cells is testosterone-driven, but clonal selection during androgen deprivation therapy promotes the development of androgen-independent (hormone-refractory) cells, which become phenotypically dominant. Human epidermal growth factor receptor type 2 (HER2) is capable of activating the androgen receptor pathway, even in the absence of the ligand. The detection of phenotypic changes associated with the development of androgen independence may influence patient management, suggesting the initiation of a second-line therapy. This study aimed to establish the level of HER2 expression in a number of prostate cancer cell lines (LNCaP, PC3 and DU145) in order that they be used as models in further studies, and to evaluate the binding and cellular processing of [In-111]-labeled trastuzumab and the anti-HER2 synthetic Affibody molecule ABY-025 in these cell lines. The expression of HER2 was demonstrated and quantified in all three tested prostate cancer cell-lines. Studies on cellular processing demonstrated that internalization of both conjugates increased continuously during the whole incubation. The internalization rate was approximately equal for both monoclonal antibodies and Affibody molecules. In both cases, internalization was moderately rapid. Such features would definitely favor the use of radiometal labels for trastuzumab and, most likely, for affibody molecules. The level of HER2 expression in these cell lines is sufficient for in vivo molecular imaging.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Rentoft, Matilda, et al.
(författare)
-
Tubulin-α-6-chain is a stably expressed reference gene in archival samples of normal oral tissue and squamous cell carcinoma of the head and neck
- 2010
-
Ingår i: Experimental and Therapeutic Medicine. - : Spandidos Publications. - 1792-0981 .- 1792-1015. ; 1:3, s. 419-423
-
Tidskriftsartikel (refereegranskat)abstract
- One of the most critical factors in gene expression studies using quantitative real-time PCR is the choice of reference gene. Many of the commonly used reference genes have been shown to vary during a number of biological processes as well as between tissues. It is therefore important to always verify the stability of the gene of choice for all new tissues and experimental conditions. Here, we used two publicly available computer software packages (GeNorm and NormFinder) to investigate the stability of eight potential reference genes in formalin-fixed paraffin-embedded (FFPE) samples from normal oral tissue of different origin as well as from oral squamous cell carcinomas. Both programs found the tubulin α-6 chain (TUBA6) and ribosomal protein S13 (RPS13) to have the most stable expression between malignant and non-malignant tissue. NormFinder also found TUBA6 to be the most stable gene when samples were grouped according to tissue origin. FFPE samples constitute a large research resource, which considerably increases the number of samples available for analysis, leading to more reliable conclusions. Verification of a proper reference gene in oral FFPE tissue is therefore of great importance for future studies.
|
|
| 15. |
- Shang, Q., et al.
(författare)
-
Clinical study of cerebral palsy in 408 children with periventricular leukomalacia
- 2015
-
Ingår i: Experimental and Therapeutic Medicine. - : Spandidos Publications. - 1792-0981 .- 1792-1015. ; 9:4, s. 1336-1344
-
Tidskriftsartikel (refereegranskat)abstract
- This study aimed to investigate the high risk factors, cerebral palsy (CP) subtypes and comorbidities of periventricular leukomalacia (PVL). Based on treatment conditions at a specialist hospital, a cross-sectional clinical study and retrospective analysis of computed tomography and magnetic resonance imaging examinations was conducted to evaluate the risk factors, subtypes and comorbidities of CP in children with PVL. Among the 408 children with PVL, 8.58% were born with a weight of 1,500 g and 44.36% were born with a weight of 2,500 g. In addition, 36.76% of these children had a gestational age of 32 weeks and 37.75% had a gestational age of 37 weeks. The proportion of the children born with various high risk factors was 95.59%, including perinatal infections and hypoxia. Severe PVL was observed in preterm infants (63.41% with a gestational age of <28 weeks and 21.95% with a gestational age of 28-30 weeks) and low-birth weight infants, which were prone to quadriplegia (43.90%). The common comorbidities included visual and auditory disorders, epilepsy, mental retardation and language barriers. Visual and auditory disorders (26.96%) were the most common comorbidities. PVL was identified primarily in premature and low-birth weight infants. The degree of PVL was found to be negatively correlated with gestational age and birth weight. The degree of PVL in the full-term infants correlated with exposure to infections or hypoxia. Quadriplegia is common among the various subtypes of CP. Visual and hearing disorders are the most common comorbidities of CP; these comorbidities occurred most frequently with quadriplegia.
|
|
| 16. |
|
|
| 17. |
- Zduniak, Krzysztof, et al.
(författare)
-
Immunohistochemical analysis of cannabinoid receptor 1 expression in steatotic rat livers
- 2016
-
Ingår i: Experimental and Therapeutic Medicine. - : Spandidos Publications. - 1792-0981 .- 1792-1015. ; 11:4, s. 1227-1230
-
Tidskriftsartikel (refereegranskat)abstract
- The primary aim of the present study was to determine the expression levels of cannabinoid receptor type 1 (CB1) in steatotic rat livers. The secondary aim was to clarify whether steatosis and inflammation are more marked in areas with increased CB1 overexpression. For ethical and economic reasons, the present study investigated tissue from archived liver blocks, which were obtained from 38 rats that had been euthanized during the course of previous research at the Karolinska Institute of the Karolinska University Hospital (Stockholm, Sweden) and Lund University (Malmö, Sweden). Liver tissue fixed in formalin and embedded in paraffin was used that had been sourced from 36 male Sprague Dawley rats (age, 7 weeks) and 2 rats (age, 180 days) lacking normal leptin receptors. The rat liver tissue was stained with antibodies against CB1 and counterstained with hematoxylin. The expression of CB1 and the number of cells overexpressing CB1 were determined. Steatosis was scored according to the Dixon scoring system. CB1 overexpression and steatosis were detected in hepatocytes from all 38 livers sampled. The expression of CB1 was more marked in hepatocytes localized next to portal triads. Near the central veins, the expression was significantly weaker. Steatosis was more marked in areas of increased CB1 overexpres with publications reporting that CB1 in hepatocytes increases lipogenesis and contributes to inflammation.
|
|
| 18. |
- Ohlsson, Bodil
(författare)
-
An Okinawan-based Nordic diet improves glucose and lipid metabolism in health and type 2 diabetes, in alignment with changes in the endocrine profile, whereas zonulin levels are elevated
- 2019
-
Ingår i: Experimental and Therapeutic Medicine. - 1792-1015.
-
Forskningsöversikt (refereegranskat)abstract
- The Okinawan-based Nordic diet has been developed to improve glucose metabolism. The aim of the present study was to summarize all anthropometric, subjective, and biochemical findings obtained following two different studies investigating this diet. The diet was administered i) as a single breakfast to healthy volunteers and ii) as a 12-week dietary intervention to patients with type 2 diabetes. The degree of satiety, sweet cravings, gastrointestinal symptoms, and health-related quality of life were estimated. Weight and blood pressures of participants were measured, and analyses including circulating levels of inflammatory and metabolic biomarkers, hormones, and short-chain fatty acids (SCFA), and microbial diversity and amount of Enterobacteriaceae in feces, were performed. A single breakfast of the diet increased satiety (P<0.001), improved glucose homeostasis (P<0.001), and lowered levels of glucose-dependent insulinotropic polypeptide (GIP) (P=0.002), compared with a standard breakfast. A 12-week intervention in type 2 diabetes increased satiety and decreased sweet cravings, at the same time as health-related quality of life and gastrointestinal symptoms were improved. There were reductions in body mass index (P<0.001), waist circumference (P<0.001), and levels of glucose (P<0.001), cholesterol (P<0.001), and triglycerides (P=0.009), in alignment with the endocrine profile. These improvements were maintained at follow-up 16 weeks later, along with lower levels of ghrelin (P=0.012), polypeptide YY (P=0.002), and visfatin (P=0.021), compared with the parameters recorded at the study start. Levels of haptoglobin, interleukin-18 and thrombocytes were lowered, whereas some other inflammatory biomarkers were unaffected and zonulin levels elevated. Gut microbiota and SCFAs levels were mainly unaffected. The mechanisms governing the anthropometric and metabolic improvements appear to be mediated through alterations in the endocrine profile, yet not in the gut microbiota.
|
|
