Luminally expressed gastrointestinal biomarkers

Introduction: A biomarker is a measurable indicator of normal biologic processes, pathogenic processes or pharmacological responses. The identification of a useful biomarker is challenging, with several hurdles to overcome before clinical adoption. This review gives a general overview of a range of biomarkers associated with inflammatory bowel disease or colorectal cancer along the gastrointestinal tract.

Areas covered: These markers include those that are already clinically accepted, such as inflammatory markers such as faecal calprotectin, S100A12 (Calgranulin C), Fatty Acid Binding Proteins (FABP), malignancy markers such as Faecal Occult Blood, Mucins, Stool DNA, Faecal microRNA (miRNA), other markers such as Faecal Elastase, Faecal alpha-1-antitrypsin, Alpha2-macroglobulin and possible future markers such as microbiota, volatile organic compounds and pH.

Expert commentary: There are currently a few biomarkers that have been sufficiently validated for routine clinical use at present such as FC. However, many of these biomarkers continue to be limited in sensitivity and specificity for various GI diseases. Emerging biomarkers have the potential to improve diagnosis and monitoring but further study is required to determine efficacy and validate clinical utility.     

Recombination adenovirus-mediated human lactoferrin cDNA inhibits the growth of human MCF-7 breast cancer cells

Objectives Human lactoferrin, an 80 kDa iron‐binding glycoprotein, has antitumour effects. We have explored the potential therapeutic role of re‐expressing human lactoferrin gene product in human breast cancer. Methods A recombinant adenovirus expressing the human lactoferrin cDNA (ad‐hLTF) was constructed and used to infect breast cancer cells. Key findings Seventy‐two hours after infection, ad‐hLTF had considerable cytotoxicity on MCF‐7 cells. A time‐course study showed that ad‐hLTF infection of MCF‐7 cells at 100 plaque‐forming units per cell increased the number of cells in G₀/G₁ phase and appeared markedly at Sub‐G₁ apoptotic peak. The presence of apoptotic cells was confirmed using Annexin V‐fluoresecein isothiocyanate apoptosis detection by flow cytometry. Ad‐hLTF also resulted in a decrease of Bcl‐2 protein and an increase in Bax protein. Conclusions Ad‐hLTF plays an important role in the induction of cell cycle arrest and apoptosis in MCF‐7 cells. The results demonstrated that ad‐hLTF could have potential benefits in the treatment of breast cancer.     

Update of fecal markers of inflammation in inflammatory bowel disease

The diagnosis, prognosis, and assessment of disease activity of inflammatory bowel disease (IBD) require investigating clinical, radiological, and histological criteria, as well as serum inflammatory markers. However, a range of fecal inflammatory markers now appears to have the potential to greatly assist in these processes. Calprotectin, a prominent neutrophil protein, was identified two decades ago as a potentially revolutionary marker for IBD. Following this discovery, numerous additional markers, including S100A12, lactoferrin, and M2-pyruvate kinase, have also been suggested as novel markers of IBD. In the present study, we provide an up-to-date review of fecal markers of IBD, and further, provide a novel analysis of each of these fecal markers in severe ulcerative colitis and compare their expression pattern in contrast to calprotectin.     

An antimicrobial protein, lactoferrin exists in the sweat: proteomic analysis of sweat

The main function of the eccrine gland has been considered to be thermoregulation. Recently, it has been reported that antimicrobial peptides including cathelicidin and dermcidin exist in the sweat. Lactoferrin is found in body fluids such as milk tears and saliva. It is known as a component of host defense against infection and inflammation. In this study, we explored whether lactoferrin is produced by eccrine glands, thereby establishing its potential role in the skin defense. By immunohistochemistry, lactoferrin was detected in eccrine glands of normal human skin. In Western blot analysis, lactoferrin was found in sweat and skin surface substances obtained from healthy volunteers. By proteomic analysis, lactoferrin and other antimicrobial peptides were detected in sweat. In addition, we measured the concentration of lactoferrin in sweat by enzyme-linked immunosorbent assay. These findings suggest that lactoferrin may contribute to skin defense against infection through its secretion in sweat.     

人乳铁蛋白对鼻咽癌细胞增殖的影响

目的：探讨重组人乳铁蛋白（hLF）对体外培养的鼻咽癌细胞生长特性的影响。方法：MTT法评价hLF对人鼻咽癌细胞CNE、人肝脏细胞L02的生长抑制作用。结果：乳铁蛋白对人鼻咽癌细胞系CNE的增殖有抑制作用并呈现剂量依赖眭,对正常细胞无抑制作用。结论：人乳铁蛋白可以抑制鼻咽癌细胞CNE的增殖。     

Emerging Health Properties of Whey Proteins and Their Clinical Implications

The nursery rhyme “Little Miss Muffet sat on a tuffet (small stool) eating her curds and whey. …” is recognition of the fact that over the centuries “curds and whey”, the two major components of cow's milk, have been widely accepted as part of a healthy diet. Milk provides complete nourishment for the neonate for six months from birth, containing factors that help develop various organ systems including the brain, immune system, and the intestine. Importantly it provides immune protection at a time when the neonates own immune system, though fully developed, is albeit immature. Many adult consumers include cow's milk as part of a healthy diet as it provides protein and essential nutrients, vitamins, and minerals, in particular calcium for strong bones. There is a growing appreciation that milk, and in particular whey, contains components that not only provide nutrition, but can also prevent and attenuate disease, or augment conventional therapies, when delivered in amounts that exceed normal dietary intakes. This paper reviews the emerging health properties of whey proteins and their clinical implications.     

Gingival crevicular fluid lactoferrin levels in adult per iodontitis patients

The present study was designed to determine in a cross-sectional study whether there was any relationship between the levels of lactoferrin in gingival crevicular fluid and clinical periodontal parameters. Crevicular fluid was collected from individual sites using standardized filter paper strips (clinically healthy sites, N=23; periodontitis sites, n=66) and evaluated for lactoferrin by enzyme-linked immunosorbent assay. The data showed that: (1) the total amounts of lactoferrin were 0.003-0.021 ng (30 second sample) (average 0.009±0.005 ng) in a clinically healthy periodontium group and 0.016-3.847 ng (30 second sample) (average 0.575±0.069 ng) in adult periodontitis patients (statistically significantly higher in adult periodontitis patients); and (2) the total amounts of lactoferrin were significantly correlated with clinical parameters,     

The relationship between elastase and lactoferrin in healthy, gingivitis and periodontitis sites

OBJECTIVES: To compare the relative amounts of elastase (primary polymorphonuclear leucocyte granule constituent) and lactoferrin (secondary PMN granule constituent) in the gingival crevicular fluid (GCF) of healthy, gingivitis and periodontitis sites.
DESIGN: This cross-sectional study looked at the two GCF constituents in three categories of disease status within the same subject.
MATERIALS AND METHODS: Patients with chronic adult periodontitis were screened and those exhibiting all three types of sites ie periodontally healthy, gingivitis and periodontitis sites were recruited (n = 10) and had GCF collected from the three sites. Lactoferrin and elastase were measured in eluates of GCF by enzyme-linked immunosorbent assay.
RESULTS: The absolute amount of lactoferrin measured in ng per 30 s samples was significantly lower in healthy and gingivitis sites as compared to periodontitis sites however this difference failed to reach significance when the concentration of lactoferrin in GCF was used as the analytical unit. No significant differences were found for elastase levels at any sites when expressed as either absolute amounts or concentrations. Secondary granule release, as evidenced by lactoferrin levels, occurs during cell migration and the process is independent of primary granule release, which is thought to correlate with PMN activation. The relationship between granule constituents in the samples showed significant differences, the highest lactoferrinlelastase ratio being at periodontitis sites (P < 0.001).
CONCLUSIONS These findings imply a change in the relative amounts of elastase and lactoferrin released at different disease level sites, with an almost 10-fold increase in the proportion of lactoferrin to elastase in periodontitis sites over healthy and gingivitis sites. This variation in the release by PMNs of primary and secondary granule constituents may indicate alterations in PMN function in different disease environments.