Biomarkers and Genomic Medicine最新文献

This study aimed to investigate whether a methanolic extract of Scurrula atropurpurea (BL.) Dans. (MESA) was able to reduced oxidative stress and systolic blood pressure (SBP) in deoxycorticosterone acetate–salt hypertensive rats. Twenty-five male Wistar were divided into the control group and four hypertensive groups that received the MESA at a doses of 50 mg/kg, 100 mg/kg, or 200 mg/kg bodyweight, or received no MESA. SBP was recorded by tail cuff methods. The levels of serum malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed by colorimetry. SBP was increased significantly in the hypertensive group compared to the sham group (p < 0.05). Administration of MESA significantly decreased SBP, but not to reach the level of the sham group. The level of MDA was significantly higher in the hypertensive group compared to the sham group (p < 0.05). Administration of MESA₂₀₀ significantly decreased the MDA levels compared to HR groups (p < 0.05). The SOD level was significantly decreased in HR compared to the sham group (p < 0.05). Administration of MESA₅₀ elevated the SOD levels to reach the level in the sham group. The SOD levels in MESA₁₀₀ and MESA₂₀₀ were significantly higher compared to the sham group (p < 0.05). In conclusion, Scurulla atropurpurea is able to modulate SOD, diminish oxidative stress, and decrease SBP in deoxycorticosterone acetate–salt hypertensive rats.

Src, a membrane-associated nonreceptor tyrosine kinase, belongs to the Src family kinase group (SFK). Dysregulation and excessive activity of Src has been reported in multiple human cancers. Src plays a critical role in many aspects of tumor development including the proliferation, survival, adhesion, invasion, and migration in multiple tumor types. Additionally, Src also plays a role in regulating the microenvironment of the cancers, and promotes the angiogenic signaling pathway for angiogenesis. However, the expression of Src in human transitional cell carcinoma is still unclear. In the current study, we demonstrated the expression level of c-Src in the human transitional cell carcinoma tissue array and compared it with normal urothelial tissues. Surprisingly, c-Src is greatly expressed in the normal urothelial tissues. However, decreasing expression of c-Src is observed in a grade-dependent manner. This finding is also confirmed in human bladder cancer cell lines. This observation shed light on a new opportunity to elucidate the pathways and biologic functions of c-Src involved in tumorigenesis, progression and prognosis of human transitional cell carcinoma. Moreover, Src inhibitors should be used with caution in cancer therapeutics to treat human transitional cell carcinoma.

Ethanol consumption during pregnancy is a widespread problem and is increasing globally among young women. Development of biomarkers of fetal alcohol syndrome (FAS), which can identify children at risk, may lead to interventions earlier in life. In addition, animal models of fetal alcohol spectrum disorders can help in novel biomarker discovery. Biomarkers of fetal alcohol spectrum disorders include classical biomarkers of alcohol-induced pathology (mean corpuscular volume, γ-glutamyl transferase, aspartate aminotransferase, and alanine aminotransferase), acetaldehyde-derived conjugates, and derivatives of nonoxidative ethanol metabolism (fatty acid ethyl esters, ethyl glucuronide, ethyl sulfate, and phosphatidyl ethanol). Because ethanol and acetaldehyde levels can be measured in blood, urine, and sweat a few hours after ethanol intake, these can be used to detect recent ethanol exposure. Magnetic resonance spectroscopic (MRS) biomarkers include N-acetyl aspartate, an indicator of neuronal density; choline, a precursor of the neurotransmitter; acetyl choline, implicated in learning and memory and in the synthesis of glycerophosphocholine (involved in membrane synthesis); and glutamate that is reduced in FAS. Glutamate is a precursor for the synthesis of γ-amino butyric acid, and creatine is required for high-energy phosphate synthesis. Furthermore, reduced brain-derived neurotropic factor, somatostatin, complexin, taurine, glutathione, myoinositol, leptin, and increased insulin-like growth factor and N-methyl D-aspartic acid receptor toxicity are observed in FAS. Impaired methionine–homocysteine cycle may also have deleterious effects on protein, DNA, and histone methylation in FAS. In addition to meconium fatty acid ethyl esters, magnetic resonance imaging, positron emission tomography, and single-photon-emission computerized tomography facilitate an earlier diagnosis of less alcohol-related disabilities that cannot be confirmed in the absence of a maternal drinking history. Brain volume, cortical volume, and cortical surface area are also reduced following prenatal exposure to ethanol. Hence, discovery of novel biomarkers is needed to define behavioral, physical, and genetic factors for better clinical management of FAS.

Mesenchymal stem cells (MSCs) from Wharton's jelly have a higher proliferation rate and self-renewal capacity than adult tissue-derived MSCs. A low oxygen level or hypoxic condition is prevalent in the microenvironment of the stem cells in the early stages of development. Hypoxia can influence proliferation and differentiation of various stem/precursor cell populations. This research was conducted: to determine the proliferation rate and characteristics of human MSCs from Wharton's jelly in hypoxic and normoxic condition; to evaluate their character after MSCs are incubated in hypoxic and normoxic environment using surface markers including CD105, CD73, CD14, CD19, CD34, CD45, and HLA-II; and to evaluate the proliferation rate and number of MSCs at many passages using the trypan blue method. The hypoxic and normoxic microenvironment showed significant differences in the proliferation rate and population doubling time, but and there were no differences in surface markers.

Hypoxia is a condition of progressive depletion of cellular oxygen, encompassing a variety of factors that have a sensitive interplay with the nucleus, DNA, and protein machinery. The relevance of hypoxia with cancer biology has been increasingly observed in recent years; however, currently there are major clinical obstacles in understanding the mechanism of tumor progression and identifying the correct therapy. This review sheds light on the most recent findings on hypoxia-induced factors that are involved in cancer progression, and relates them to a network of signals that are co-involved in tumor growth. In this perspective, this review elaborates on unanswered key questions with regard to regulation and modulation pathways related to oxygen-deprived conditions during cancer development, including a brief view of specific microRNA factors in hypoxia. The focus of this review is on the vast landscape of components that are involved in tumor progression, including identification of potential targets and pathways that can play a pivotal role in identifying clinical and diagnostic methods, with hypoxia as a starting point. Defining novel and potential cell cycle factors is of significant importance, particularly given the increasing emergence of personalized medicine.

This study deals with the detection of serum p53 antigen concentration by enzyme-linked immunosorbent assay as a marker for TP53 gene mutation in gastric cancer patients, correlating it with p53 protein expression detected by immunostaining. The serum concentration of p53 antigen ranged from 0.28 ng/mL to 0.59 ng/mL [average 0.40 ± 0.08 ng/mL, (p < 0.001) compared to the normal control (average 0.19 ± 0.11 ng/mL)]. Positive serum p53 protein concentrations were detected in 29 (36.3%) out of 80 patients, according to adopting a cut-off value for serum p53 protein concentration of 0.42 ng/mL. This corresponded to a value of 2 SD (standard deviations) above the mean value from the healthy controls. Expression of p53 protein was detected in 62.5% (40 of 64) of the nuclei in carcinoma cells from gastric cancer patients. The average serum p53 antigen concentration in the positive immunostained cases was 0.42 ± 0.08 ng/mL, with significant elevation compared with that in the negative immunostained cases (0.36 ± 0.06 ng/mL; p < 0.02). Therefore, serum p53 antigen concentration would be expected to be a useful marker for gastric cancer.

Warfarin is a commonly prescribed oral anticoagulant used for prophylaxis and treatment of deep vein thrombosis, myocardial infarction, heart valve replacement, pulmonary embolisms, and other thromboembolic disorders. Because overdosing of warfarin is fatal to patients and only a few studies are available on the Indian population, the present study was undertaken to develop genotyping assays for the monitoring of patients undergoing warfarin therapy specific to the Indian population. Warfarin dosing is correlated with polymorphisms in VKORC1 (vitamin K epoxide reductase complex 1) and CYP2C9 (cytochrome P450 family 2, subfamily C, polypeptide 9) genes. Hence, this study was undertaken to assess the impact of these genetic variations (SNPs) in VKORC1 and CYP2C9 genes of Indian patients on warfarin therapy. In the present study, genomic DNA samples from 136 individuals (patients on stabilized warfarin therapy) were analyzed through polymerase chain reaction (PCR) and DNA sequencing. Furthermore, the observed SNPs were correlated with the dosage pattern in order to understand the genotype–phenotype correlation significance. Additionally, an amplification refractory mutation system PCR-based genotyping assay was developed for the VKORC1 –1639G>A allele, as a rapid and cost-effective detection tool. The analysis of samples from warfarin-sensitive patients showed that 84.78% of participants had mutant alleles in either the CYP2C9 or the VKORC1 gene. A novel mutation with an insertion of G at 3725 position (Ins-G –1586 with respect to the start codon) in the promoter region of the VKORC1 gene—along with the VKORC1 –1639G>A allele—was observed in four patients, all of whom were on a higher dosage of warfarin (>7 mg/d). Our results clearly indicate that there is a variation in the dosage pattern associated with the VKORC1 –1639G>A genotype in the presence of this novel promoter insertion, further suggesting the need for large-scale studies to be conducted on Indian populations for the validation of warfarin sensitivity tests.

Septicemia is a major cause of death in neonates. Prompt diagnosis and effective treatment is necessary to treat patients with septicemia. However, the prevalence, etiology, and antibiotic susceptibility vary with location and time. This study aimed at determining the prevalence of neonatal septicemia and the effect of age and gender on this prevalence. In addition, the antibacterial susceptibility of etiologic agents was also determined. Blood samples were collected from 534 neonates (322 males and 212 females) between 1 day and 28 days of age with signs and symptoms of septicemia. The blood samples were processed to diagnose septicemia. Identification of bacterial isolates and disc susceptibility testing were performed using standard techniques. Age and gender did not significantly affect the prevalence of neonatal septicemia (p = 0.554 and 0.127, respectively). Klebsiella species were the predominant microorganism causing neonatal septicemia, in males and within the first 14 days of life. Fluoroquinolones, gentamicin, and β-lactams (with the exception of cloxacillin) were the most active antibacterial agents. An overall neonatal septicemia prevalence rate of 38.95% was observed. Klebsiella species was the most predominant isolate causing neonatal septicaemia. The β-lactam antibiotics recommended in susceptibility testing and the data collected in this study will be helpful in empiric therapy of neonatal septicemia.

The study identified the most effective fraction and subfraction of hydro-methanolic extract (2:3) of the seed of Tamarindus indica Linn. (T. indica) having antidiabetic activity in rats with diabetes induced by streptozotocin (STZ). The effective fraction and subfraction of T. indica were subjected to an antidiabetic study in STZ-induced diabetic rats at two dose levels, 100 mg/kg and 25 mg/kg body weight twice a day. Serum insulin, glycosylated hemoglobin, carbohydrate metabolic enzymes, and transaminases were assessed and the histopathology of the pancreas was examined after 8 weeks of treatment and compared to the vehicle control. Treatment of n-hexane fraction at a dose of 100 mg/kg twice a day for 56 days in STZ-induced diabetic rat resulted in a significant reduction in fasting blood glucose and glycosylated hemoglobin levels along with a rise in serum insulin and glycogen contents in hepatic and skeletal muscle in comparison to chloroform, ethyl acetate, or n-butanol fraction treated groups as well as the untreated diabetic group. The most antidiabetic activity of n-hexane fraction had been highlighted by the activities of hexokinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, and lactate dehydrogenase in the liver, kidney, cardiac, and skeletal muscle in respect with groups treated with other fractions. Two subfractions, A and B, were obtained from the n-hexane fraction using petroleum ether, of which subfraction B was more bioactive considering the above biosensors and was comparable with glibenclamide, a standard antihyperglycemic drug. Chromatographic study by high performance thin layer chromatography focused on two components of subfraction B, P₁ and P₂ where P₁ is predominant, conformed by high performance liquid chromatography. The dose of subfraction B was 25 mg/kg twice a day i.e., 1/4 dose of the n-hexane fraction. The n-hexane fraction and subfraction B of T. indica are free from hepatic and renotoxicity according to the study of serum transaminase.

This study aimed to evaluate the antidiabetic activity of Strychnos potatorum seeds in streptozotocin-nicotinamide–induced diabetes in experimental animals. Noninsulin-dependent diabetes mellitus (NIDDM) was induced in overnight fasted rats by an intraperitoneal injection (i.p.) of 60 mg/kg streptozotocin (STZ) and, after a 15-minute interval, 120 mg/kg of nicotinamide. S. potatorum extract 200 mg/kg or 400 mg/kg body weight was administered orally to the rats once daily for 21 days. The blood glucose level was assessed by a glucometer. The serum levels of cholesterol, triglycerides, and total lipid were determined by using diagnostic kits. Measurement of catalase (CAT), superoxide dismutase (SOD), glutathione–S-transferase (GST), reduced glutathione (GSH), and glutathione peroxidase (GPx) were determined to ascertain the antioxidant activity. A significant reduction in the blood glucose level was observed in diabetic animals treated with the different doses of the extract, compared to untreated diabetic rats. The treatment with the extract significantly increased the levels of GSH, GPx, GST, CAT, and SOD in the drug-treated group to levels comparable to the levels in the diabetic control group. The result of this study thus shows that 50% of the ethanolic extract at different doses possesses significant antidiabetic activity and potent antioxidant potential in diabetic conditions.