Regulation of CDK inhibitor p27 by microRNA 222 in breast cancer patients.

BACKGROUND: Breast cancer is the most common of all cancers and the second leading cause of cancer-related deaths among women worldwide. MicroRNAs regulate at least 60% of the human genes, including tumor suppressor genes and oncogenes, and can thereby affect cancer risk. In this study, the prognostic values of the CDK inhibitor p27 and miR-222 as biomarkers for breast cancer were evaluated. METHODS: The real-time quantitative polymerase chain reaction method was employed to measure the expression level of miR-222, whereas the serum levels of the CDK inhibitor p27 were measured via enzyme-linked immunosorbent assay. The levels were determined in sera from 110 participants representing three different groups. RESULTS: Patients with breast cancer exhibited significantly higher expression levels of miR-222 and lower levels of CDK inhibitor p27 than the control group. In addition, a statistically significant inverse correlation between miR-222 and the CDK inhibitor p27 was observed. The receiver operating characteristic curves plotted for serum p27 and miR-222 helped in significantly differentiating between breast cancer patients and controls but could not discriminate between those with stage II and stage III cancer. CONCLUSION: Thus, a significant upregulation in the serum miR-222 levels was observed in cancer patients, and a significant inverse correlation was noted between the miR-222 and CDK inhibitor p27 expression levels. These findings indicate that miR-222 may be used as a useful noninvasive screening biomarker for human breast cancer. MICROABSTRACT: Novel biomarkers for prognosis, prediction, and therapeutic purposes are essential as the prognosis and therapeutic targets of breast cancer are dependent on traditional markers, such as the tumor stage and hormonal receptor status. This study aimed to evaluate the diagnostic and prognostic values of the CDK inhibitor p27 and miR-222 in breast cancer. Our results indicated that miR-222 and the CDK inhibitor p27 may be used as noninvasive biomarkers to screen for human breast cancer but cannot discriminate between patients with early breast cancer and patients with advanced breast cancer.

It Is Not Always Alcohol Abuse--A Transferrin Variant Impairing the CDT Test.

AIMS: Elevated Carbohydrate-deficient transferrin (CDT) levels are used as a biomarker in order to screen for chronic alcohol abuse. Transferrin (Tf) variants can impair methods to measure elevated CDT levels such as high-performance liquid chromatography (HPLC). We present a Tf variant affecting the second glycosylation site of Tf and the complications it causes in diagnosing alcoholism. METHODS: A blood sample from a patient with suspected alcohol abuse was analyzed with HPLC, isoelectric focusing, electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS), immunoprecipitation and SDS-Page. Sanger sequencing of Tf was performed to detect Tf mutations. RESULTS: HPLC, SDS-Page and IEF showed a distinctly increased disialo-Tf fraction while the tetrasialo-Tf fraction was decreased, ESI-TOF-MS confirmed these results. Sanger sequencing revealed the Tf mutation c.1889 A>C, deleting a Tf glycosylations site and thereby causing elevated disialo-Tf levels. CONCLUSIONS: Transferrin mutations can severely impair the diagnostics of chronic alcohol abuse by causing false positive results. This has to be considered when CDT screening is used to detect alcoholism.

Does Moderate Altitude Affect VO2max in Acclimatized Mountain Guides?

Pühringer, Reinhard, Hannes Gatterer, Martin Berger, Michael Said, Martin Faulhaber, and Martin Burtscher. Does moderate altitude affect VO2max in acclimatized mountain guides? High Alt Med Biol. 23:37-42, 2022. Background: Altitude exposure reduces maximal oxygen uptake (VO2max). Usually, the reduction is not restored with acclimatization (at least at altitudes above 2,500 m) and is more pronounced in highly trained athletes compared to nonathletes. It still remains to be elucidated whether these also apply for well-acclimatized individuals (i.e., mountain guides) acutely exposed to moderate altitude (i.e., 2,000 m). Methods: A total of 128 acclimatized male mountain guides of the Austrian armed forces (42.2 ± 7.0 years, 177.8 ± 5.6 cm, 77.2 ± 7.0 kg) of different fitness levels performed 2 incremental cycle ergometer tests 1 week apart, one at low (600 m) and one at moderate altitude (2,000 m). Oxygen uptake, heart rate (HR), and lactate concentration were measured during the tests. Results: In acclimatized mountain guides, lower baseline VO2max levels were associated with better preservation of VO2max at moderate altitude compared to higher levels. At moderate altitude, physiological responses (HR and blood lactate at 100 W) at a submaximal exercise intensity of 100 W remained unchanged or were even slightly reduced in both groups. Conclusions: Long-term acclimatization to moderate altitude may prevent the VO2max decline at a moderate altitude of 2,000 m particularly in subjects with lower VO2max levels, that is, below the 80th percentile (for age and sex). In people with higher fitness levels, VO2max may still be negatively affected. These results are of practical relevance, for example, for workers, athletes, ski and mountain guides, military staff, or rescue staff who regularly or continuously have to perform at moderate altitude.

Age-Dependent Health Status and Cardiorespiratory Fitness in Austrian Military Mountain Guides.

Puehringer, Reinhard, Martin Berger, Michael Said, and Martin Burtscher. Age-dependent health status and cardiorespiratory fitness in Austrian military mountain guides. High Alt Med Biol. 21:346-351, 2020. Background: Mountaineering activities (at moderate and high altitudes) require a relatively high level of physical fitness, which may be closely associated with healthy aging. This cross-sectional study was aimed at evaluating the age-dependent health status and fitness level in Austrian military mountain guides. Methods: A total of 166 professional mountain guides were recruited for a comprehensive health check and exercise testing. Comparisons were made between 3 different age groups, that is, ≤40 years (n = 74), 41-50 years (n = 70), and >50 years (n = 22). Besides exercise capacity, anthropometric, biomedical, and cardiorespiratory parameters have been assessed. Results: None of the assessed parameters differed between age group 1 and 2. A slight increase was observed in the age group 3 concerning body weight, body mass index, blood lipids, blood glucose, and urea levels, and resting systemic blood pressure values. Peak aerobic capacity and maximal heart rates were slightly lower in this age group than the younger groups. When compared with the general population, mountain guides of similar age showed lower prevalence of being overweight, and suffering from systemic hypertension and diabetes. Conclusions: Our findings indicate favorable aging of mountain guides occupationally performing mountaineering activities (at moderate and high altitudes), characterized by maintaining a high fitness level and developing reduced cardiovascular risk factors until older than 50 years.

Cardiovascular risk factors and atherosclerosis in young males: ARMY study (Atherosclerosis Risk-Factors in Male Youngsters).

BACKGROUND: Necropsy studies suggest that atherosclerosis begins in childhood, but in vivo confirmation of this concept is sparse and limited to selected population samples. Furthermore, new risk concepts of atherosclerosis focusing on inflammation, infections, and immunity have not yet been evaluated in this age group. METHODS AND RESULTS: This study was conducted in a sample of 141 17- to 18-year-old white males homogenous in age and sex. In addition to classic risk factors, C-reactive protein and the humoral and cellular immune reactivity to heat-shock proteins (HSPs) were assessed. Intima-media thickness (IMT) was quantified at 4 vessel segments of the carotid and femoral arteries. High IMT was considered to be present if the IMT of at least 1 vessel segment exceeded the 90th percentile. In a multivariate logistic regression analysis, cigarette smoking, high diastolic blood pressure, prominent immune reactivity to human and/or mycobacterial HSP60s, alcohol consumption (inverse), and low HDL cholesterol levels were all associated with high IMT. The prevalence of high IMT substantially increased from 0 to 60% when the number of risk conditions in a single individual increased from 0 to 4 (P<0.001 for linear trend). CONCLUSIONS: Our study supports the concept that atherosclerosis begins in the first decades of life and suggests a role of the immune system, especially immunoreactivity against HSP60s, in atherosclerosis of young individuals.

Implementation and interpretation of hydrogen breath tests.

Hydrogen breath tests are non-invasive and safe diagnostic tools used to investigate functional intestinal disorders. For the diagnosis of fructose or lactose malabsorption as well as for the detection of small intestinal bacterial overgrowth syndrome, hydrogen breath tests are even regarded as gold standard. However, standardization of the testing procedure and the interpretation of the test results are still lacking. In this paper, reliable information on the implementation of the most common hydrogen breath tests and precise guidelines for the interpretation of the test results are presented.