Blood endotyping distinguishes the profile of vitiligo from that of other inflammatory and autoimmune skin diseases

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Comprehensive analysis of key lncRNAs in HCV-positive hepatocellular carcinoma

IntroductionHepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Despite the therapeutic advances in HCC in the past few decades, the mortality rate of HCC is still high. Hepatitis C (HCV) infection is one of the major etiological risk factors of HCCs. However, the underlying mechanisms of HCV-induced hepatocarcinogenesis remain largely unclear.Material and methodsOur study represented the comprehensive analysis of differentially expressed lncRNAs in HCV-positive HCC for the first time by analyzing the public dataset {"type":"entrez-geo","attrs":{"text":"GSE17856","term_id":"17856"}}GSE17856. Co-expression network and gene ontology (GO) analysis revealed the functions of those differentially expressed lncRNAs.ResultsWe identified 256 upregulated lncRNAs and 198 downregulated lncRNAs in HCV- positive HCC compared to the normal liver tissues. Co-expression network and GO analysis showed that these lncRNAs were involved in regulating metabolism, energy pathways, proliferation and the immune response. Seven lncRNAs (LOC341056, CCT6P1, PTTG3P, LOC643387, LOC100133920, C3P1 and C22orf45) were identified as key lncRNAs and co-expressed with more than 100 differentially expressed genes (DEGs) in HCV-related HCC. Kaplan-Meier analysis showed that higher expression levels of LOC643387, PTTG3P, LOC341056, CCT6P1 and lower expression levels of C3P1 and C22orf45 were associated with shorter survival time in the TCGA dataset.ConclusionsWe believe that this study can provide novel potential therapeutic and prognostic biomarkers for HCV-positive HCC.     

The biomolecules of beauty: biochemical pharmacology and immunotoxicology of cosmeceuticals

ABSTRACT

Many ingredients in cosmetic products help to develop complex formulations that improve the quality of life in terms of disease prevention, health maintenance, beauty enhancement, and building self-esteem. The beneficial effects promoted from the use of biomolecule-rich substances into the formulations of various topical application products are considered useful ingredients in cosmetic and therapeutic applications. This review article attempts to understand the various biomolecules found in cosmetic products, particularly macromolecules, which may have an important role in prevention or preservation. Increasing demand of cosmetics all over the world has increased the awareness related to safety issue. Cosmetic products may contain potential contact allergens or precursors that can be oxidized or metabolized to generate contact allergens which can potentially cause allergic reactions or dermatitis. These substances can pose hazards to human health due to their ability to activate T cells that can cause allergic contact dermatitis, an inflammatory skin disease. Finally, the simultaneous on-site measurement of different substances from a single sample, called multiplexed point-of-care testing, has recently become increasingly important for the in vitro quantification of pathological or toxicological samples. Hence, the technological advancements in clinical sciences will be helpful in the identification of ingredients in cosmetic preparations.     

The use of proteomics in biomarker discovery in neurodegenerative diseases

Biomarkers for neurodegenerative diseases should reflect the central pathogenic processes of the diseases. The field of clinical proteomics is especially well suited for discovery of biomarkers in cerebrospinal fluid (CSF), which reflects the proteins in the brain under healthy conditions as well as in several neurodegenerative diseases. Known proteins involved in the pathology of neurodegenerative diseases are, respectively, normal tau protein, beta-amyloid (1-42), synaptic proteins, amyloid precursor protein (APP), apolipoprotein E (apoE), which previously have been studied by protein immunoassays. The objective of this paper was to summarize results from proteomic studies of differential protein patterns in neurodegenerative diseases with focus on Alzheimer's disease (AD). Today, discrimination of AD from controls and from other neurological diseases has been improved by simultaneous analysis of both beta-amyloid (1-42), total-tau, and phosphorylated tau, where a combination of low levels of CSF-beta-amyloid 1-42 and high levels of CSF-tau and CSF-phospho-tau is associated with an AD diagnosis. Detection of new biomarkers will further strengthen diagnosis and provide useful information in drug trials. The combination of immunoassays and proteomic methods show that the CSF proteins express differential protein patterns in AD, FTD, and PD patients, which reflect divergent underlying pathophysiological mechanisms and neuropathological changes in these diseases.     

Alcoholic and Non-Alcoholic Beer Modulate Plasma and Macrophage microRNAs Differently in a Pilot Intervention in Humans with Cardiovascular Risk

Beer is a popular beverage and some beneficial effects have been attributed to its moderate consumption. We carried out a pilot study to test if beer and non-alcoholic beer consumption modify the levels of a panel of 53 cardiometabolic microRNAs in plasma and macrophages. Seven non-smoker men aged 30–65 with high cardiovascular risk were recruited for a non-randomised cross-over intervention consisting of the ingestion of 500 mL/day of beer or non-alcoholic beer for 14 days with a 7-day washout period between interventions. Plasma and urine isoxanthohumol were measured to assess compliance with interventions. Monocytes were isolated and differentiated into macrophages, and plasma and macrophage microRNAs were analysed by quantitative real-time PCR. Anthropometric, biochemistry and dietary parameters were also measured. We found an increase in plasma miR-155-5p, miR-328-3p, and miR-92a-3p after beer and a decrease after non-alcoholic beer consumption. Plasma miR-320a-3p levels decreased with both beers. Circulating miR-320a-3p levels correlated with LDL-cholesterol. We found that miR-17-5p, miR-20a-5p, miR-145-5p, miR-26b-5p, and miR-223-3p macrophage levels increased after beer and decreased after non-alcoholic beer consumption. Functional analyses suggested that modulated microRNAs were involved in catabolism, nutrient sensing, Toll-like receptors signalling and inflammation. We concluded that beer and non-alcoholic beer intake modulated differentially plasma and macrophage microRNAs. Specifically, microRNAs related to inflammation increased after beer consumption and decreased after non-alcoholic beer consumption.     

Effect of Weight Loss by Low-Calorie Diet on Cardiovascular Health in Type 2 Diabetes: An Interventional Cohort Study

Cardiovascular disease (CVD) remains a major problem for people with type 2 diabetes (T2DM), and the leading cause of death worldwide. We aimed to determine cardiovascular benefits of weight loss with or without remission of diabetes, and to assess utility of plasma biomarkers. 29 people with T2DM were studied at baseline and after dietary weight loss. Change in plasma adipokines and lipid related markers was examined in relation to weight loss, diabetes remission, 10-year cardiovascular risk (QRISK), and duration of diabetes. QRISK decreased markedly after weight loss (18.9 ± 2.2 to 11.2 ± 1.6%, p < 0.0001) in both responders and non-responders, but non-responders remained at higher risk (15.0 ± 2.0 vs. 5.8 ± 1.6%, p < 0.0001). At baseline, plasma GDF-15 was higher in longer diabetes duration (1.19 ± 0.14 vs. 0.82 ± 0.09 ng/mL, p = 0.034), as was the QRISK (22.8 ± 2.6 vs. 15.3 ± 3.4%, p = 0.031). Leptin, GDF-15 and FGF-21 decreased whereases adiponectin increased after weight loss in responders and non-responders. However, the level of FGF-21 remained higher in non-responders (0.58 [0.28–0.71] vs. 0.25 [0.15–0.42] ng/mL, p = 0.007). QRISK change correlated with change in plasma VLDL1-TG (r = 0.489, p = 0.007). There was a positive correlation between rise in HDL cholesterol and the decrease in leptin (r = 0.57, p = 0.001), or rise in adiponectin (r = 0.58, p = 0.001) levels. In conclusion, weight loss markedly decreases cardiometabolic risk particularly when remission of diabetes is achieved. Leptin, adiponectin, GDF-15 and FGF-21 changes were related to weight loss not remission of diabetes. Normalization of 10-year cardiovascular risk and heart age is possible after substantial dietary weight loss and remission of T2DM.     

Plasma and Urinary Amino Acid-Derived Catabolites as Potential Biomarkers of Protein and Amino Acid Deficiency in Rats

Objective: Dietary intakes must cover protein and essential amino acid (EAA) requirements. For this purpose, different methods have been developed such as the nitrogen balance method, factorial method, or AA tracer studies. However, these methods are either invasive or imprecise, and the Food and Agriculture Organization of the United Nations (FAO, 2013) recommends new methods and, in particular, metabolomics. The aim of this study is to determine total protein/EAA requirement in the plasma and urine of growing rats. Methods: 36 weanling rats were fed with diets containing 3, 5, 8, 12, 15, and 20% protein for 3 weeks. During experimentation, urine was collected using metabolic cages, and blood from the portal vein and vena was taken at the end of the experiment. Metabolomics analyses were performed using LC-MS, and the data were analyzed with a multivariate analysis model, partial least Squares (PLS) regression, and independent component-discriminant analysis (ICDA). Each discriminant metabolite identified by PLS or ICDA was tested by one-way ANOVA to evaluate the effect of diet. Results: PLS and ICDA allowed us to identify discriminating metabolites between different diet groups. Protein deficiency led to an increase in the AA catabolism enzyme systems inducing the production of breakdown metabolites in the plasma and urine. Conclusion: These results indicate that metabolites are specific for the state of EAA deficiency and sufficiency. Some types of biomarkers such as AA degradation metabolites appear to be specific candidates for protein/EAA requirement.     

When is the right time to take an emergency surgery decision in Mechanical Intestinal Obstruction?

Background/Objective: Ischemia is a leading cause of morbidity in Mechanical Intestinal Obstruction (MIO) in which the timing of decisions of whether to proceed to surgical or conservative treatment is critical in emergency departments (ED). While advanced technological options are available, patients may be negatively affected by the application of contrast agents or radiation. The use of ultrasound is limited because of the air in the intestines does not allow a good field of vision. While biomarkers can be considered as a good alternative option at this point. In the present study we examine the effect of hemogram and blood gas parameters on early surgical decision-making in MIO patients.MethodInvolved in this observational prospective study were 264 patients diagnosed with MIO who presented to the Department of Emergency Medicine, Ataturk Research and Training Hospital, Katip Celebi University between February 2018 and February 2019. Contrast-enhanced tomography (CECT) and laboratory results of the patients were recorded. Pathology reports of the patients who underwent surgery were collected. Laboratory data were analyzed by comparing CECT and pathology reports.ResultsIn a ROC analysis of the laboratory values of the patients who were diagnosed with ileus, the sensitivity was calculated as 80% and the specificity was 57.7 in values above WBC>10.75 (10⁹/L), 96.6%, and the specificity was 31.1% in N/L > 2.9. For intestinal ischemia, the cut-off values were WBC> 12.6 and N/L > 3.2, Lactate >2.8 mmol/L and B.E < -3.6 mmol/L.ConclusionDiagnoses of ileus are based on the results examinations and imaging methods. More data are needed to support decisions on the timing of surgery in ED. WBC, N/L, Lactate and Base Excess indicate an ischemic segment. When the parameters are evaluated together, they strongly support early surgical decision-making regarding the treatment of intestinal ischemia.     

Laboratory tests of renal function

The kidneys are vital organs in the management of fluid balance, waste product removal, electrolyte homeostasis, acid–base balance and endocrine function. Waste products removed by the kidney are urea, uric acid and creatinine; other foreign products with similar physiochemical properties are also excreted. Urea and uric acid are by products of protein metabolism and creatinine is generated by the metabolism of creatine compounds from muscle. The kidney regulates fluid and electrolyte balance through controlling the composition and volume of urine. In the proximal convoluted tubule and the loop of Henle, 90% of sodium, potassium, calcium and magnesium are reabsorbed. Acid–base balance is achieved by regulating the excretion of hydrogen ions and bicarbonate buffering. The kidney also has a number of endocrine functions including the production of renin and erythropoietin as well as hydroxylation of vitamin D. The kidneys receive 25% of cardiac output, generating 170–200 litres of ultrafiltrate per day. Urine output is approximately 1.5 litres per day, which is concentrated ultrafiltrate through selective reabsorption of solutes and water. In this article we will discuss tests frequently used to assess renal function.