Biomarkers and Genomic Medicine最新文献

This study aimed to investigate the effects of electrical injury on vascular damage and on matrix metalloproteinase (MMPs) levels. Thirty male Wistar albino rats were divided into five groups (n = 6), including a control group (untreated group), a 600 mv electrical burn injury group, a 900 mv electrical burn injury group, a 1200 mv electrical burn injury group, and a 1500 mv electrical burn injury group. Endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) were analyzed using flow cytometry. The levels of MMP-9, MMP-3, nitric oxide (NO), vascular endothelial growth factor (VEGF), and vascular cell adhesion molecule (VCAM) were assayed using an enzyme linked immunosorbent assay. Levels of EPCs were significantly lower in all electrical burn injury groups compared with the control group (p < 0.05). The levels of NO and VEGF were significantly increased in all electrical burn injury groups compared with the control group (p < 0.05). The levels of MMP-9 were significantly higher in the 1200 mv electrical burn injury group compared with the control group or the 900 mv electrical burn injury group (p < 0.05). There were no significant differences in MMP-3, VCAM, and CECs levels between groups (p > 0.05). This electrical burn injury model shows a significant decrease in endothelial progenitor cells and an increase in VEGF, NO, and MMP-9 as the compensating mechanism.

This study aimed to elucidate whether CSN1S2 protein of goat's milk was able to inhibit pro-inflammatory cytokine [interleukin (IL)-17 and tumor necrosis factor (TNF)-α], RAGE, and caspase-3 expression in rheumatoid arthritis (RA) rats. A total of 24 Wistar female rats, were randomly assigned into four groups: control group (C), CSN1S2 protein of goat's milk group (CM), CFA-induced RA-rats group (RA), and the RA group treated by CSN1S2 protein of goat's milk (RAM). The severity of erythema and swelling in lower extremities were counted by scoring. IL-17, TNF-α, RAGE, and caspase-3 expression in synovial membranes were analyzed by confocal laser scanning microscopy (CLSM) and western blotting. Erythema and swelling in the RA group was significantly attenuated by goat's milk CSN1S2 (p < 0.05), but did not reach the level in the control group (p < 0.05). The use of CLSM, CSN1S2 protein of goat's milk could decrease the TNF-α, caspase-3, and the number of hyperplasia cells in comparison with the RA group (p < 0.05), to reach the level in the control group (p > 0.05). Western blotting analysis showed that the expression of IL-17, RAGE, TNF-α, and caspase-3 were higher in the RA group compared with the control group. CSN1S2 protein of goat's milk decreased RAGE and TNF-α expression, but increased the IL-17 and caspase-3 expression. In conclusion, CSN1S2 protein of goat's milk decreased erythema, swelling, and inflammation in lower extremities. The CSN1S2 protein of goat's milk also decreased TNF-α and RAGE expression in the synovial membrane of ankle joints. Unfortunately, CSN1S2 protein of goat's milk may induce the production of IL-17. Therefore CSN1S2 protein of goat's milk may provide a nutritional therapy for attenuating the inflammation found in rheumatoid arthritis.

Vascular dementia (VaD) affects a broad spectrum of patients with various manifestations of cognitive decline, which could be attributed to cerebrovascular or cardiovascular disease. Diagnosis of VaD depends on the identification of environmental and genetic risk factors including; cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Mitochondrial oxidative stress, hypoxic ischemia, inflammation, accumulation of advanced glycation products, and proinflammatory cytokines have been implicated in the pathogenesis of VaD. Hence it is exceedingly important to determine the risk factors and molecular pathology by identifying specific biomarkers that can be broadly classified as: biochemical, molecular, genetic, endocrinological, anatomical, imaging, and neuropathological; for the early differential diagnosis, prognosis, and effective treatment of VaD. The biomarkers of VaD in the serum and cerebrospinal fluid samples include; phosphorylated tau, amyloid-β, matrix metalloproteases, sulfatids, albumin, and proinflammatory C-reactive proteins. In addition, Charnoly body (CB) formation and microRNAs can be detected as preapoptotic biomarkers of compromised mitochondrial bioenergetics to further confirm VaD. CB formation occurs in response to nutritional stress and/or neurotoxic insult in the most vulnerable hippocampal neurons due to cerebrovascular insufficiency, and can be attenuated by dietary interventions, physiological zinc supplementation, and metallothioneins (MTs). MTs provide ubiquinone-mediated neuroprotection by serving as free radical scavengers, by maintaining the mitochondrial redox balance, by inhibiting CB formation, and by inhibiting progressive neurodegenerative α-synucleinopathies. MTs also regulate zinc-mediated transcriptional activation of genes involved in cell growth, proliferation, and differentiation, and hence may be used as novel biomarkers of VaD. In addition to genetic analysis of MTs, Notch3, apolipoprotein E4, nitric oxide synthase, and cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy; omics and microRNA analyses may provide novel biomarkers of VaD. This review provides recent update on in-vitro biomarkers from the serum and cerebrospinal fluid samples and in-vivo neuroimaging biomarkers for the differential diagnosis and effective clinical management of VaD.

Spondyloarthritis presents clinical features, laboratory findings, and similar images, but their clinical manifestations reveal great heterogeneity in patients HLA-B*27 positive and negative. This study compared the frequencies of the clinical manifestations in the presence and absence of HLA-B*27. From the 156 patients with clinical suspicion of spondyloarthritis, 73 had a diagnosis of spondyloarthritis confirmed. The HLA-B*27 gene was identified by polymerase chain-reaction sequence-specific oligonucleotide probe (PCR-SSOP). The Student t test was used to calculate the values of mean and the Fisher's exact test was used to compare proportions. The values of odds ratio (OR) and confidence interval (CI) at 95% were also calculated (p < 0.05). The spondyloarthritis found were: ankylosing spondylitis (n = 47, 64.4%), psoriatic spondyloarthritis (n = 9, 12.3%), undifferentiated spondyloarthritis (n = 9, 12.3%), enteropathic spondyloarthritis (n = 6; 8.2%) and reactive spondyloarthritis (n = 2, 2.7%). Overall, 35 (47.9%) patients were HLA-B*27 positive and 38 (52.1%) were negative. This gene was associated with ankylosing spondylitis (OR: 5.37, 95% CI: 1.813–15.905, p = 0.003) but not with enteropathic spondyloarthritis (OR: 0.07, 95% CI: 0.003–1.301, p = 0.025). The sacroiliitis was associated with HLA-B*27 positive (OR: 10.552, 95% CI: 1.260–88.256, p = 0.014) and intestinal injury with HLA-B*27 negative (OR: 0.195, 95% CI: 0.038–0.978, p = 0.048). The image signals sacroiliitis were associated with the HLA-B*27 gene while intestinal involvement was not associated with this gene.

Novel alkylsulfonated chitosan, produced by alkylsulfonation, has become a water-soluble, anionic polymer due to the existence of hydrophilic alkylsulfonic acid group. The alkylsulfonic acid creates specific exchangeable cations, thereby increasing the antimicrobial effectiveness and skin tissue compatibility. Alkylsulfonated chitosan demonstrated outstanding microorganism inhibition against fungal reference strains of Malassezia furfur (BCRC 22243), Malassezia pachydermatis (BCRC 21676), Trichophyton rubrum (BCRC 32805), Trichophyton mentagrophytes (BCRC 32066), and Candida albicans (BCRC 20518), together with four different bacteria species of Escherichia coli (BCRC 11509), Pseudomonas aeruginosa (BCRC 11864), Staphylococcus aureus (BCRC 10781), and Propionibacterium acne (BCRC 10723). Meanwhile, our results indicate that alkylsulfonated chitosan works well in growth inhibition of microorganism strains tested at pH 5–6 and at pH 7.

Epidermal growth factor receptor (EGFR) is a member of the transmembrane receptor tyrosine kinase family. In normal and malignant cells, activation of the EGFR cascade is involved in the regulation of various cellular activities. The objective of this study was to identify and assess associations of positive EGFR expression and K-RAS mutations with various clinicopathological parameters and survival of colorectal carcinoma patients. EGFR of colorectal cancer (CRC) tissue specimens was subjected to immunohistochemical analysis, polymerase chain reaction, and DNA sequencing. Immunohistochemical staining was performed using monoclonal antibodies against EGFR antigens and examination of mutations was performed to detect mutations in codons 12 and 13 of the K-RAS. Statistical analysis was performed using SPSS version 16.0. The results of this study showed that of the 40 study participants, 62.5% (25/40) showed positive EGFR overexpression. Of the patients showing positive EGFR expressions, 52% had mutations in the K-RAS. Mutations were spread in codon 12 (64.3%) and codon 13 (35.7%) and there was one sample with mutations in codons 12 and 13 at the same time. A statistically significant association was found between the presence of metastasis and EGFR overexpression and survival of CRC patients. In addition, a significant association was found between K-RAS mutations and metastasis and survival of CRC patients. In conclusion, EGFR overexpression and K-RAS mutations were found in CRC patients. Both factors are known to be associated with poor prognosis of cancer patients in terms of patient survival. Early detection of K-RAS mutations in CRC patients is a crucial component in the determination of the type of therapy and treatment for the patient.

Atherosclerosis occurs as a result of the oxidation of low-density lipoprotein (LDL) deposits, which later form plaques. Hyperglycemia, which occurs in patients with type 2 diabetes mellitus, is a risk factor for this kind of vascular damage. Oxidative stress from hydrogen peroxide (H₂O₂) is increased in patients with hyperglycemia and therefore an antioxidant agent is required to prevent the destruction of the walls of blood vessels. This study aimed to show that Ganoderma lucidum polysaccharide peptide (PsP) can decrease the formation of H₂O₂. The study was an experimental in vivo post-test with control group design. Thirty-five Wistar rats (Rattus norwegicus) were divided into five groups (a normal diet group, a hypercholesterol diet group, and hypercholesterol groups that received doses of 50 mg/kg, 150 mg/kg, and 300 mg/kg body weight PsP). The parameters determined in this study were the level of H₂O₂, the lipid profile, insulin resistance, and the amounts of perivascular adipocyte tissue (PVAT), foam cells, and plaques. Each treatment group showed significant results for the administration of PsP using the one-way analysis of variance test (p < 0.050) for the reduction of H₂O₂ (p = 0.003), the lipid profile (cholesterol total and triglyceride; p = 0.010, p = 0.001), insulin resistance (p = 0.003), the amount of PVAT (p <0.001), and plaques (p <0.001). The decrease in foam cells was insignificant (p = 0.149), although an obvious pattern of reduction as a result of PsP treatment was observed. PsP from G. lucidum is a potent antioxidant and may prevent the pathophysiology of atherosclerosis in patients with type 2 diabetes mellitus. The optimum dose in patients with type 2 diabetes mellitus is 300 mg/kg body weight. Further studies are required to determine the antioxidant effects of G. lucidum PsP and its benefits in the management of type 2 diabetes mellitus.

The aim of the present study was to evaluate the in vitro antioxidant activities of the hydro-methanol (2:3) extract of the seeds of Swietenia mahagoni (L.) Jacq. To evaluate the antioxidant activity, the effects of the extract on the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging effect, scavenging of hydrogen peroxide, hydroxyl radical scavenging potential, scavenging of nitric oxide, and antilipid peroxidation activity by biochemical methods were examined. Total phenol and flavonoid content in the extract were measured biochemically as per standard methods. Results indicated that the hydro-methanol (2:3) extract had strong scavenging activity on the DPPH radical with an IC₅₀ value 80.54 μg/mL, the hydroxyl radical with an IC₅₀ value 60.76 μg/mL, and hydrogen peroxide with an IC₅₀ value 66.10 μg/mL. The hydro-methanol (2:3) extract also showed notable inhibition of lipid peroxidation with an IC₅₀ value 61.23 μg/mL and nitric oxide with an IC₅₀ value of 81.56 μg/mL. Phytochemical study showed that the extract is rich in phenolic compounds [46.25 mg gallic acid equivalent (GAE)/g dried extract] and flavonoids [231.72 μg quercetin equivalent (QE)/g dried extract]. The present study provides evidence that the hydro-methanol (2:3) extract of seeds of S. mahagoni is a potential source of natural antioxidant activities.

Mesenchymal stem cells (MSCs) have unique properties, including high proliferation rates, self-renewal, multilineage differentiation ability, wide multipotency, hypoimmunogenicity, noninduction of teratomas, and anticancer properties. MSCs can be isolated from embryonic and extraembryonic tissues as well as adult organs. Human Wharton's jelly stem cell-conditioned medium possesses anticancer properties and inhibits the growth of solid tumors. Lower oxygen concentration or hypoxic condition can increase the proliferation of MSCs, but there are no differences in surface markers. We determined the osteocyte, chondrocyte, and adipocyte differentiation of normoxic WJMSCs (nor-WJMSCs) and hypoxic 2.5%, hypoxic 5% (hypo-WJMSCs); from a different passage (P4 and P8), we determined the inhibitory effect of WJMSCs-norCM and WJMSCs-hypoCM on the proliferation of human cancer cells including cervical (HeLa), liver (HepG2), prostate (pc3), ovarian (skov3), and oral squamous (hsc3) cancer cell lines compared to normal cells including mouse fibroblast (NIH3T3), human fibroblast, and human mesenchymal stem cells (hMSCs). Surfacer marker expression of nor-WJMSCs-and hypo-WJMSCs from P4 and P8 were >95% for CD90, CD73 and CD105 and <2% for CD14, CD19, CD34, CD45, and HLDA-II. Nor-WJMSCs and hypo-WJMSCs from P4 and P8 underwent differentiation to osteocyte, chondrocyte, and adipocyte. WJMSCs-norCM and WJMSCs-hypoCM could inhibit proliferation of various cancer cell lines with minimum inhibitory concentration (IC₅₀) 51.690–81.440% and cause low inhibition of the normal cells with IC50 136.290–185.339%. WJMSCs-norCM and WJMSCs-hypoCM were not cytotoxic toward normal cells. Nor-WJMSCs and hypo-WJMSCs from P4 and P8 showed no significant differences in MSC surface marker expression or differentiation. WJMSCs-norCM and WJMSCs-hypoCM could inhibit proliferation in various cancer cell lines, and were safe for normal cells.