The potential role of human HIV-1 TAT-Interactive Protein 2 levels in the pathogenesis of contact dermatitis

Background/aim: Human HIV-1 TAT interactive protein 2 (HTATIP2/TIP30) is a gene that is extensively expressed in human tissues as well as in tumor tissues. This study aimed to explore the potential role of HTATIP2/TIP30 in contact dermatitis (CD), which is one of the most common inflammatory cutaneous conditions. Materials and methods: This cross-sectional study involved adult patients with acute contact dermatitis who were admitted to the outpatient dermatology clinic of a tertiary hospital and healthy adult volunteers without any cutaneous or systemic diseases. The blood concentration of HTATIP2/TIP30 was measured using ELISA kits. Results: The research sample consisted of 31 patients with CD (18 males, 13 females) and 20 healthy control subjects (14 males, 6 females). The mean ages of the patients with CD and healthy volunteers were 37 and 30 years, respectively (p > 0.05). The mean value of serum HTATIP2/TIP30 levels in patients with CD was 1.65 ng ml­1, which is 0.60 ng ml­1 in the control group (p = 0.02) Conclusion: In this study, serum levels of HTATIP2/TIP30 were statistically significantly higher in patients with CD when compared to healthy controls. This outcome may indicate possible role of HTATIP2/TIP30 in the pathogenesis of CD.

Clinical significance of changes in AFP, HTATIP2/TIP30, B7-H4 and inflammatory cytokines after transcatheter arterial chemoembolization.

PURPOSE: To explore the clinical significance of changes in alpha-fetoprotein (AFP), HIV-1 TAT interactive protein 2/TAT interactive protein 30 (HTATIP2/TIP30), B7-H4 and inflammatory cytokines after transcatheter arterial chemoembolization (TACE). METHODS: A total of 84 hepatocellular carcinoma (HCC) patients admitted to the Department of Hepatobiliary Surgery and the Department of Interventional Radiology of our hospital from January 1, 2017 to December 31, 2018 were randomly enrolled and divided into an experimental group and a control group according to treatment methods. The expression levels of AFP mRNA, HTATIP2/TIP30, B7-H4 and inflammatory cytokines were detected before and after treatment, the short-term efficacy was followed up and analyzed, and the correlation between the two was statistically analyzed. RESULTS: The AFP expression level in the two groups of patients was lower after treatment than before treatment, this reduction being more obvious in the experimental group (receiving TACE) than in the control group. Although the levels of serum HTATIP2/TIP30 and B7-H4 were decreased after treatment in both groups, and they were lower after treatment than those before treatment in the control group, lower levels were registered in the control group. Both groups of patients had lower expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) after treatment compared with those before treatment, this decrease being more significant in the experimental group than in the control group. Moreover, the total short-term efficacy rate and the improvement rate of the quality of life were higher in the experimental group than in the control group, although no statistical difference in the survival rate was found between the two groups after 1-year follow-up. The serum level of B7-H4 in the group with good efficacy was lower than in the group with poor efficacy before treatment, and it declined in both groups after treatment, with a lower level in the former than in the latter. Furthermore, the group with good efficacy had a lower level of serum HTATIP2/TIP30 than the group with poor efficacy, while both groups had a decreased level after treatment, with a lower level in the former than in the latter. CONCLUSION: Interventional therapy for primary HCC has good short-term efficacy. It can reduce the levels of serum HTATIP2/TIP30, B7-H4, AFP and inflammation-related indexes, improve the liver function and the patients' quality of life.

Combined detection of AFP-L3, GP73 and TIP30 enhances diagnostic accuracy for HBV-related cirrhosis and hepatocellular carcinoma.

OBJECTIVE: To investigate the value of combined tests of serum Golgi protein-73, alpha-fetoprotein- L3 and Tat-interacting protein-30 in the diagnosis of hepatitis B virus related cirrhosis and hepatocellular carcinoma. METHODS: The cross-sectional study was conducted at Yuebei People's Hospital, Guangdong, China, from January to October 2017, and comprised hepatitis B patients and healthy controls. Serum Golgi protein-73, alpha-fetoprotein-L3 and Tat-interacting protein-30 levels in both groups were detected by enzyme-linked immunosorbent assay (ELISA). Alpha-fetoprotein-L3 was separated and quantified by electrochemiluminescence immunoas says and the percentage of alpha-fetoprotein-L3 to alphafetoprotein was calculated. RESULTS: Of the 721 subjects, 525(%) were patients and 196(%) were healthy controls. Among the patients, 271(%) had chronic hepatitis B, 161(%) had liver cirrhosis and 93(%) had hepatocellular carcinoma. Serum Golgi protein-73, alpha-fetoprotein-L3 and Tat-interacting protein-30 levels were significantly different in the hepatocellular carcinoma patients compared to controls, and those with chronic hepatitis and liver cirrhosis (p<0.01 each). The sensitivity and specificity of the combined detection of the three serum levels for diagnosing cirrhosis were 78.26% and 86.72%. The corresponding values for diagnosing hepatocellular carcinoma were 86.02% and 92.51%. CONCLUSIONS: Combined detection of Golgi protein-73, alpha fetoprotein-L3 and Tat-interacting protein was found to have the potential to improve diagnostic accuracy.

The effects of interventional therapy on serum HTATIP2/TIP30, B7-H4 and short-term curative effect in primary hepatocellular carcinoma.

OBJECTIVE: To explore the effects of interventional therapy on human immunodeficiency virus (HIV)-1 Tat interactive protein 2/Tat interactive protein 30 (HTATIP2/TIP30), B7-H4 and short-term curative effect in primary hepatocellular carcinoma. PATIENTS AND METHODS: 62 patients with primary hepatocellular carcinoma admitted in our hospital from June 2015 to June 2016 were enrolled in this study and divided into observation group (n = 31) and control group (n = 31) according to the random number table. The patients in the control group were treated with radiofrequency ablation, and the patients in the observation group were treated with transcatheter arterial chemoembolization (TACE). The patients in both groups received liver protection therapy, hydration, antiemetic and stomach protection. The curative effects, the serum HTATIP2/TIP30, B7-H4, alanine aminotransferase (ALT) and total bilirubin in serum (TBIL), life quality before and after treatment, and survival during the 1-year follow-up, were compared. RESULTS: The total short-term effective rate (70.97%) was higher than the control group (38.71%) (p < 0.05). The serum levels of HTATIP2/TIP30 and B7-H4 were decreased after treatment in both groups (observation group: t = 17.1838, 18.9795, control group: t = 8.3787, 10.6393, p < 0.05). The serum levels of HTATIP2/TIP30 and B7-H4 after treatment in the observation group were lower than the control group (t = 12.2975, 10.5361, p < 0.05). The levels of ALT and TBIL were decreased after treatment (observation group: t = 15.1716, 34.5771, control group: t = 8.3374, 17.3015, p < 0.05). The levels of ALT and TBIL were lower in the observation groups than the control group (t = 15.2697, 16.8592, p < 0.05). The improvement rate of life quality in the observation group (80.65%) was higher than the control group (54.84%) (p < 0.05). The survival rates of the two groups after 1-year follow-up were not statistically different (p > 0.05). CONCLUSIONS: The short-term curative effect of interventional therapy of primary hepatocellular carcinoma is good. It can decrease serum HTATIP2/TIP30 and B7-H4, improves the liver function and the life quality of patients, prolonging the survival time. It has a high research value and it is worthy of further application.

Advanced Liver Fibrosis Is Independently Associated with Palmitic Acid and Insulin Levels in Patients with Non-Alcoholic Fatty Liver Disease.

Changes in lipid metabolism occur during the development and progression non-alcoholic fatty liver disease (NAFLD). However, the fatty acid (FA) profile in red blood cells (RBC) from patients with liver fibrosis remains unexplored. Thus, the goal of this study was to evaluate the fatty acid profile in RBC, dietary lipid intake and insulin resistance indicators in patients with NAFLD, according to the degree of hepatic fibrosis. Using elastography, patients were classified with (n = 52) and without (n = 37) advanced liver fibrosis. The fatty acid profile in RBC was analyzed using gas chromatography and the lipid intake was evaluated through a 24-h dietary recall. Subjects with advanced liver fibrosis had higher levels of palmitic, stearic and oleic acid and total monounsaturated fatty acid (MUFA) and insulin (p < 0.05), and lower levels of elongase very long chain fatty acids protein-6 and the delta-5-desaturase enzymatic activity (p < 0.05). These results suggest a lack of regulation of enzymes related to FA metabolism in patients with advanced fibrosis.

Associations Among Fatty Acids, Desaturase and Elongase, and Insulin Resistance in Children.

OBJECTIVES: Fatty acid profiles and desaturase (SCD-16, SCD018, D5D, D6D) and elongase (ELOVL6) enzyme activity have been associated with adiposity and metabolic disease. While this has been studied in adults, few studies have included children. The objective of this study was to evaluate these markers in children and identify relationships with markers of metabolic health. It was hypothesized that these lipid markers would be correlated to adiposity and metabolic disease. METHODS: This study was a cross-sectional analysis of fourth- and fifth-grade children (n = 86, aged 9-12) participating in a comprehensive nutrition program. Any student enrolled in the program was eligible for inclusion in this study. Fasting plasma was collected and analyzed for total fatty acids, glucose, insulin, and full lipid panels. Insulin resistance was estimated using calculated homeostatic model assessment for insulin resistance (HOMA-IR) values. RESULTS: There were no differences in lipid markers, glucose, insulin, or HOMA-IR among children classified as normal weight, overweight, or obese. SCD-16, D5D, and ELOVL6 activity was significantly correlated to HOMA-IR values (r = 0.39, p = 0.001; r = -0.33, p = 0.006; r = -0.37, p = 0.005, respectively). In regression analysis, body mass index for age percentile, D6D activity, ELOVL6 activity, and systolic blood pressure were the most significant predictors of HOMA-IR values (adjusted r2 = 0.39, p ≤ 0.001). CONCLUSIONS: There was no relationship between these lipid markers and adiposity in this population; however, there were correlations with HOMA-IR. Regardless of adiposity, there may be underlying changes in fatty acid and lipid metabolism associated with the development of metabolic diseases.

Role of disturbed fatty acids metabolism in the pathophysiology of diabetic erectile dysfunction.

BACKGROUND: Vasculogenic erectile dysfunction (VED) is considered as a common complication among people with type 2 diabetes (T2D). We tested whether changes in fatty acid (FAs) classes measured in erythrocytes are associated with increased risk of diabetic VED along with related risk factors. METHODS: We assessed erythrocyte FAs composition, lipid peroxidation parameters and inflammatory cytokines among 72 T2D men with VED, 78 T2D men without VED and 88 healthy volunteers with similar age. Biochemical, hepatic, lipid and hormonal profiles were measured. RESULTS: T2D people with VED had significant decrease in the indexes of Δ6-desaturase and elongase activities compared to the other studied groups. The same group of participants displayed lower erythrocytes levels of dihomo-γ-linolenic acid (C20:3n-6) (P < .001), precursor of the messenger molecule PGE1 mainly involved in promoting erection. Moreover, absolute SFAs concentration and HOMA IR levels were higher in T2D people with VED when compared to controls and associated with impaired NO concentration (1.43 vs 3.30 ng/L, P < .001). Our results showed that IL-6 and TNF-α were significantly increased and positively correlated with MDA levels only in T2D people with VED (r = 0.884, P = .016 and r = 0.753, P = .035; respectively) suggesting a decrease in the relative availability of vasodilator mediators and an activation of vasoconstrictors release. CONCLUSION: Our findings show that the deranged FAs metabolism represents a potential marker of VED in progress, or at least an indicator of increased risk within men with T2D.

Mycothiol acetyltransferase (Rv0819) of Mycobacterium tuberculosis is a potential biomarker for direct diagnosis of tuberculosis using patient serum specimens.

Mycobacterium tuberculosis infection constitutes a global threat that results in significant morbidity and mortality worldwide. Efficient and early diagnosis of tuberculosis (TB) is of paramount importance for successful treatment. The aim of the current study is to investigate the mycobacterial mycothiol acetyltransferase Rv0819 as a potential novel biomarker for the diagnosis of active TB infection. The gene encoding Rv0819 was cloned and successfully expressed in Escherichia coli. The recombinant Rv0819 was purified using metal affinity chromatography and was used to raise murine polyclonal antibodies against Rv0819. The raised antibodies were employed for direct detection of Rv0819 in patient serum samples using dot blot assay and competitive enzyme-linked immunosorbent assay (ELISA). Serum samples were obtained from 68 confirmed new TB patients and 35 healthy volunteers as negative controls. The dot blot assay showed sensitivity of 64·7% and specificity of 100%, whereas the competitive ELISA assay showed lower sensitivity (54·4%) and specificity (88·57%). The overall sensitivity of the combined results of the two tests was found to be 89·7%. Overall, the mycobacterial Rv0819 is a potential TB serum biomarker that can be exploited, in combination with other TB biomarkers, for efficient and reliable diagnosis of active TB infection. SIGNIFICANCE AND IMPACT OF THE STUDY: The early and accurate diagnosis of tuberculosis infection is of paramount importance for initiating treatment and avoiding clinical complications. Most current diagnostic tests have poor sensitivity and/or specificity and in many cases they are too expensive for routine diagnostic testing in resource-limited settings. In the current study, we examined a novel mycobacterial serum biomarker, namely mycothiol acetyltransferase Rv0819. The antigen was detectable in serum specimens of a significant number of tuberculosis patients. This article proves the importance of Rv0819 and paves the way towards its future use as a useful diagnostic marker for tuberculosis infection.

MCM2 and TIP30 are prognostic markers in squamous cell/adenosquamous carcinoma and adenocarcinoma of the gallbladder.

The clinicopathological and biological characteristics of squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder remain to be fully elucidated, due to the fact that it is a rare gallbladder cancer subtype. In the current study, the expression of minichromosome maintenance complex component 2 (MCM2) and HIV­1 tat interactive protein 2 (TIP30) was measured in 46 cases of SC/ASC and 80 adenocarcinomas (AC) using immunohistochemistry. Positive MCM2 and negative TIP30 expression were significantly associated with large tumor size, high TNM stage, invasion, lymph node metastasis and lack of surgical curability in SC/ASC and AC. Positive MCM2 and negative TIP30 expression were significantly associated with poor differentiation in AC, whereas only MCM2 was correlated with differentiation in SC/ASC. Univariate Kaplan­Meier analysis demonstrated that positive MCM2 and negative TIP30 expression, the degree of differentiation, tumor size, TNM stage, invasion, lymph node metastasis and surgical curability were significantly associated with post­operative survival in patients with SC/ASC and AC. Multivariate Cox regression analysis demonstrated that positive MCM2 and negative TIP30 expression, the degree of differentiation, tumor size, TNM stage, invasion, lymph node metastasis and lack of surgical curability were also independent predictors of poor prognosis in patients with SC/ASC and AC. These data suggest that positive MCM2 and negative TIP30 expression are closely correlated with the clinical, pathological and biological parameters, in addition to poor prognosis in patients with gallbladder cancer.

Long-chain saturated and monounsaturated fatty acids associate with development of premature infants up to 18 months of age.

Myelination is important perinatally and highly dependent on long-chain saturated and monounsaturated fatty acids. Long-chain polyunsaturated fatty acids, nowadays often supplemented, inhibit oleic acid synthesis. Using data from a premature cohort, we studied if nervonic, lignoceric and oleic acids correlated to growth and early development up to 18 months corrected age. Small for gestational age infants had lower concentrations than infants appropriate for gestational age. Only oleic acid was negatively correlated to long-chain polyunsaturated fatty acids. Oleic and lignoceric acids correlated to social interaction at one month, and nervonic acid to mental, psychomotor and behavioral development at 6, 10 and 18 months, also when adjusted for several confounders. Negative association between oleic acid and long-chain polyunsaturated fatty acids suggests inhibition of delta-9 desaturase, and nervonic acid´s divergent correlation to lignoceric and oleic acids suggests different metabolism in neonatal period. Our results may have implications for the supplementation of premature infants.

Cancer-Specific Production of N-Acetylaspartate via NAT8L Overexpression in Non-Small Cell Lung Cancer and Its Potential as a Circulating Biomarker.

In order to identify new cancer-associated metabolites that may be useful for early detection of lung cancer, we performed a global metabolite profiling of a non-small cell lung cancer (NSCLC) line and immortalized normal lung epithelial cells from the same patient. Among several metabolites with significant cancer/normal differences, we identified a unique metabolic compound, N-acetylaspartate (NAA), in cancer cells-undetectable in normal lung epithelium. NAA's cancer-specific detection was validated in additional cancer and control lung cells as well as selected NSCLC patient tumors and control tissues. NAA's cancer specificity was further supported in our analysis of NAA synthetase (gene symbol: NAT8L) gene expression levels in The Cancer Genome Atlas: elevated NAT8L expression in approximately 40% of adenocarcinoma and squamous cell carcinoma cases (N = 577), with minimal expression in all nonmalignant lung tissues (N = 74). We then showed that NAT8L is functionally involved in NAA production of NSCLC cells through siRNA-mediated suppression of NAT8L, which caused selective reduction of intracellular and secreted NAA. Our cell culture experiments also indicated that NAA biosynthesis in NSCLC cells depends on glutamine availability. For preliminary evaluation of NAA's clinical potential as a circulating biomarker, we developed a sensitive NAA blood assay and found that NAA blood levels were elevated in 46% of NSCLC patients (N = 13) in comparison with age-matched healthy controls (N = 21) among individuals aged 55 years or younger. Taken together, these results indicate that NAA is produced specifically in NSCLC tumors through NAT8L overexpression, and its extracellular secretion can be detected in blood. Cancer Prev Res; 9(1); 43-52. ©2015 AACR.

Protective effects of vitamin E against liver damage caused by renal ischemia reperfusion.

Recent studies have reported that remote organs are affected by renal ischemia reperfusion (IR). The present study investigates the role of vitamin E on the liver damage after renal IR. First, male mice were subjected to three groups (n = 9): 1) sham-operated, (2) renal IR (45 min ischemia), (3) renal IR + Vitamin E (150 mg/kg trough feeding tube for 28 d). After 24 h of reperfusion, animal were anesthetized for sample collections. Liver tissues malondialdehyde (MDA) increased and total glutathione (GSH) concentration decreased in the IR group compared to the sham group. Vitamin E consumption diminished the IR-induced increase in plasma AST and ALT. In addition, Vitamin E inhibited the IR-induced decrease in GSH activity and diminished IR-induced increase in MDA concentration. These findings showed that vitamin E consumption partly inhibited the IR-induced liver damage.

Psychiatric blood biomarkers: avoiding jumping to premature negative or positive conclusions.

Blood biomarkers may provide a scientifically useful and clinically usable peripheral signal in psychiatry, as they have been doing for other fields of medicine. Jumping to premature conclusions, negative or positive, can create confusion in this field. Reproducibility is a hallmark of good science. We discuss some recent examples from this dynamic field, and show some new data in support of previously published biomarkers for suicidality (SAT1, MARCKS and SKA2). Methodological clarity and rigor in terms of biomarker discovery, validation and testing is needed. We propose a set of principles for what constitutes a good biomarker, similar in spirit to the Koch postulates used at the birth of the field of infectious diseases.

Biomarkers of psychiatric diseases: current status and future prospects.

Abnormal behavior and disturbed cognition, often assumed to represent psychiatric illness, may actually result from some form of occult organic brain disease that can be detected by means of one or more biomarkers. This truth was discovered more than a century ago by Aloysius Alzheimer, a German psychiatrist and neuropathologist. As a psychiatrist, he described the behavioral manifestations of "senile dementia" in a 51-year-old female; as a neuropathologist, he was the first to recognize the significance of the senile plaques and neurofibrillary tangles found in her brain after her death at age 55 years. It was Alzheimer who made the connection between these "biomarkers" and the symptoms of the increasingly prevalent disease that now bears his name. In recent years, the search for psychiatry-relevant biomarkers of major depression, schizophrenia, bipolar disease, and other important psychiatric/neuropsychiatric disorders has intensified. Biomarkers in psychiatry and neuropsychiatry have the potential of clarifying the etiology of an ambiguous clinical presentation-making it possible, for example, to detect underlying differences between psychological maladies that have confusingly similar symptoms. In addition, attempts are now being made to classify mental disorders on the basis of biomarkers. Biomarkers may also disclose the presence of a previously unsuspected physical explanation for behavior(s) originally presumed to be "psychiatric" in origin. Although clinically usable biomarkers in the diagnosis and treatment of mental illness await validation, candidate genomic biomarkers and protein profiling of candidate biomarkers in psychiatry are rapidly gaining ground as areas of interest, with considerable future potential. This review considers biomarker-related issues germane to psychiatry and neuropsychiatry in the context of new data that can be used to tailor therapies to the individual psychiatric patient.

The relation of diet with PAF and its metabolic enzymes in healthy volunteers.

PURPOSE: Platelet-activating factor (PAF), a potent inflammatory mediator, is implicated in atherosclerosis. Its key biosynthetic enzymes are lyso-PAF acetyltransferases (lyso-PAF-AT), responsible for PAF synthesis through the remodeling route and a specific CDP-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-CPT), responsible for its de novo biosynthesis. PAF acetylhydrolase (PAF-AH) and its extracellular isoform lipoprotein-associated phospholipase A2 catabolize PAF. The impact of diet on PAF metabolism is ill-defined. The aim was to investigate associations between PAF, its enzymes and dietary factors. METHODS: One-hundred and six (n = 106) healthy volunteers were recruited. Food-frequency questionnaires, dietary recalls, lifestyle and biochemical variables were collected. Food groups, macronutrient intake, a priori (MedDietScore) and a posteriori defined food patterns with PCA analysis, dietary antioxidant capacity (DAC), glycemic index (GI) and glycemic load were assessed. RESULTS: PAF was inversely correlated with antioxidant-rich foods (herbal drinks and coffee), the DAC as well as a dietary pattern characterized by legumes, vegetables, poultry and fish (all Ps < 0.05). PAF was positively correlated to % fat intake. Lyso-PAF-AT was also negatively associated with healthy patterns (fruits, nuts and herbal drinks, and a pattern rich in olive oil and whole-wheat products), as well as the DAC and % monounsaturated fatty acids. PAF-CPT was negatively associated with GI and coffee intake and positively with dietary cholesterol. PAF-AH was negatively associated with coffee and positively associated with alcohol consumption (all Ps < 0.05). CONCLUSIONS: In conclusion, the DAC and healthy dietary patterns were inversely associated with PAF or its biosynthetic enzymes, suggesting potential new mechanisms of the diet-disease associations.

Genetic determinants influencing human serum metabolome among African Americans.

Phenotypes proximal to gene action generally reflect larger genetic effect sizes than those that are distant. The human metabolome, a result of multiple cellular and biological processes, are functional intermediate phenotypes proximal to gene action. Here, we present a genome-wide association study of 308 untargeted metabolite levels among African Americans from the Atherosclerosis Risk in Communities (ARIC) Study. Nineteen significant common variant-metabolite associations were identified, including 13 novel loci (p<1.6 × 10(-10)). These loci were associated with 7-50% of the difference in metabolite levels per allele, and the variance explained ranged from 4% to 20%. Fourteen genes were identified within the nineteen loci, and four of them contained non-synonymous substitutions in four enzyme-encoding genes (KLKB1, SIAE, CPS1, and NAT8); the other significant loci consist of eight other enzyme-encoding genes (ACE, GATM, ACY3, ACSM2B, THEM4, ADH4, UGT1A, TREH), a transporter gene (SLC6A13) and a polycystin protein gene (PKD2L1). In addition, four potential disease-associated paths were identified, including two direct longitudinal predictive relationships: NAT8 with N-acetylornithine, N-acetyl-1-methylhistidine and incident chronic kidney disease, and TREH with trehalose and incident diabetes. These results highlight the value of using endophenotypes proximal to gene function to discover new insights into biology and disease pathology.

High serum HTATIP2/TIP30 level in serous ovarian cancer as prognostic or diagnostic marker.

BACKGROUND: Human HIV-1 TAT interactive protein 2 (HTATIP2/TIP30) is an evolutionarily conserved gene that is expressed ubiquitously in human tissues and some tumor tissues. This protein has been found to be associated with some gynecological cancers; as such, this study aimed to investigate blood HTATIP2/TIP30 levels in patients with ovarian cancer. METHODS: Twenty-three women with ovarian cancer and 18 patients with various non-cancerous gynecological complaints (for example, dysfunctional uterine bleeding, fibroids, and urinary incontinence) were included in the study. The pathological diagnosis of ovarian cancer was adenocarcinoma. HTATIP2/TIP30 concentration in the patients' blood samples was determined using ELISA kits. RESULTS: The HTATIP2/TIP30 level was significantly higher in the cancer group than in the control group (1.84 ± 0.82 versus 0.57 ± 0.13 ng/ml, mean ± SD). CONCLUSIONS: We demonstrated the potential role of HTATIP2/TIP30 in ovarian cancer for the first time, thereby enlightening future studies targeting HTATIP2/TIP30 in ovarian cancer treatment, diagnosis, and prevention.

Percentage oleic acid is inversely related to percentage arachidonic acid in total lipids of rat serum.

BACKGROUND: Since many health effects of oils rich in oleic acid (18:1, n-9) seem to be opposite those of arachidonic acid (20:4, n-6), i.e. concerning cardiovascular risk, we examined whether % 18:1 might be negatively associated with % 20:4. METHODS: Fatty acid separation by gas chromatography was performed in total serum lipids of 36 male rats. Using bivariate correlations and multiple linear regressions we studied the association between oleic acid and arachidonic acid. RESULTS: We found an inverse relationship (r = -0.885, p < 0.001; n = 36) between percentages of 18:1 and 20:4 in total lipids of rat serum, persisting when controlling for the other fatty acids measured. In a multiple linear regression model with % 20:4 as the dependent variable and percentages of the other fatty acids entered simultaneously as independents, oleic acid and linoleic acid contributed most to predict % 20:4. Per cent 20:4 correlated negatively (p< 0.01) with a Delta-9 desaturase index, i.e. the (18:1)/(18:0) ratio, and with the (20:4)/(18:2) ratio, estimating desaturases/elongase. CONCLUSIONS: Percentages of 18:1 and 20:4 seem to be inversely related and desaturase/elongase inhibition could be involved. The results might partly explain positive health effects of foods rich in oleic acid.

Paricalcitol effects on activities and metabolism of platelet activating factor and on inflammatory cytokines in hemodialysis patients.

PURPOSE: Paricalcitol improves the inflammatory status of hemodialysis patients. PAF is a strong inflammatory mediator which is produced during hemodialysis. We studied the effects of paricalcitol on PAF and other inflammatory mediators implicated in chronic kidney disease (CKD). METHODS: We examined the in vitro effects of paricalcitol on PAF/thrombin-induced aggregation as well as on the activities of PAF-basic metabolic enzymes, lyso-PAF acetyltransferase (Lyso-PAF-AT), DTT-insensitive CDP-choline: 1-alkyl-2-acetyl-sn-glycerol cholinephospho-transferase (PAF-CPT) and PAF-acetylhydrolase (PAF-AH) in blood cells from healthy volunteers. In addition, the in vivo effects of paricalcitol on the above these enzymes were examined in plasma and blood cells of hemodialysis patients who had not received any type of vitamin D treatment during the last three months before and after receiving paricalcitol for a month. Finally, IL-12p70, IL-1ß, IL-6, IL-8 and TNF-α were measured. RESULTS: Paricalcitol inhibited in vitro PAF/thrombin-induced platelet aggregation and the inhibitory effect was comparable with that of PAF/thrombin antagonists. In addition, paricalcitol inhibited in vitro PAF-CPT activity in platelets and leukocytes and increased PAF-AH activity in leukocytes, while much higher concentrations of paricalcitol were needed to inhibit Lyso-PAF-AT activity. Similarly, in hemodialysis patients, paricalcitol treatment reduced PAF-CPT activity in platelets and leukocytes and increased PAF-AH activity in leukocytes, while it could not influence Lyso-PAF-AT activity. On the other hand, paricalcitol therapy reduced IL-8, IL-1ß, and TNF-α. CONCLUSIONS: These results further support the beneficial effects of vitamin D treatment in hemodialysis patients, since it strongly affects PAF/thrombin activities, PAF-metabolism, and IL-8, IL-1ß and TNF-α circulating levels.

Methylation of ELOVL2 gene as a new epigenetic marker of age.

The discovery of biomarkers able to predict biological age of individuals is a crucial goal in aging research. Recently, researchers' attention has turn toward epigenetic markers of aging. Using the Illumina Infinium HumanMethylation450 BeadChip on whole blood DNA from a small cohort of 64 subjects of different ages, we identified 3 regions, the CpG islands of ELOVL2, FHL2, and PENK genes, whose methylation level strongly correlates with age. These results were confirmed by the Sequenom's EpiTYPER assay on a larger cohort of 501 subjects from 9 to 99 years, including 7 cord blood samples. Among the 3 genes, ELOVL2 shows a progressive increase in methylation that begins since the very first stage of life (Spearman's correlation coefficient = 0.92) and appears to be a very promising biomarker of aging.