Bile Salt-stimulated Lipase Research Articles

Comparative proteomic analysis of donor human milk treated by high-pressure processing or Holder pasteurization on undigested proteins across dynamic simulated preterm infant digestion

High-pressure processing (HPP) of donor human milk (DM) minimally impacts the concentration and bioactivity of some important bioactive proteins including lactoferrin, and bile salt-stimulated lipase (BSSL) compared to Holder pasteurization (HoP), yet the impact of HPP and subsequent digestion on the full array of proteins detectable by proteomics remains unclear. We investigated how HPP impacts undigested proteins in DM post-processing and across digestion by proteomic analysis. Each pool of milk (n = 3) remained raw, or was treated by HPP (500 MPa, 10 min) or HoP (62.5 °C, 30 min), and underwent dynamic in vitro digestion simulating the preterm infant. In the meal, major proteins were minimally changed post-processing. HPP-treated milk proteins better resisted proximal digestion (except for immunoglobulins, jejunum 180 min) and the extent of undigested proteins after gastric digestion of major proteins in HPP-treated milk was more similar to raw (e.g., BSSL, lactoferrin, macrophage-receptor-1, CD14, complement-c3/c4, xanthine dehydrogenase) than HoP.

Changes in Digestive Enzyme Activities during Larval Development of Spotted Seatrout (Cynoscion nebulosus)

The spotted seatrout (Cynoscion nebulosus)—an important commercial species—has a high potential for aquaculture in the Gulf of Mexico. To optimize its feeding during larval rearing, this study aims to evaluate the primary gastric (pepsin), intestinal (leucine aminopeptidase and alkaline phosphatase), and pancreatic (alkaline protease, trypsin, chymotrypsin, amylase, and lipase) enzyme activities from hatching to day 30. A multivariate analysis identified three digestive enzyme development stages during the spotted seatrout larval transformation. The first stage occurred between 1 (mean ± standard error (SE) = 1.73 ± 0.14 millimeter (mm) standard length (SL)) and 3 (2.14 ± 0.07 mm SL) days after hatching (DAH); a period of digestive stability showed the highest activity in amylase and bile salt-dependent lipase. The second stage (from 4 (2.53 ± 0.09 mm SL) to 20 (10.92 ± 0.51 mm SL) DAH) was a period of digestive transition, during which leucine aminopeptidase, chymotrypsin, and alkaline proteases were identified as the predominant enzymes from 4 to 5 DAH. In the third stage—a period of digestive stability—pepsin was the major enzyme that occurred between 25 (16.51 ± 0.81 mm SL) and 30 (25.91 ± 0.82 mm SL) DAH. These results indicate that the spotted seatrout larvae have a digestive system adapted to lipids and carbohydrates at the onset of feeding, with an immediate transition to protein digestion when exogenous feeding begins. Additionally, the digestive system of the spotted seatrout may be considered mature at 25 DAH. Further research is needed to elucidate the mechanisms of digestive tract development in the spotted seatrout larvae.

Breast milk preservation: thermal and non-thermal processes and their effect on microorganism inactivation and the content of bioactive and nutritional compounds.

Human Breast Milk (HBM) is widely acknowledged as the best nutritional source for neonates. Data indicates that, in 2019, 83.2% of infants in the United States received breast milk at birth, slightly reducing to 78.6% at 1 month. Despite these encouraging early figures, exclusive breastfeeding rates sharply declined, dropping to 24.9% by 6 months. This decline is particularly pronounced when direct breastfeeding is challenging, such as in Neonatal Intensive Care Units (NICU) and for working mothers. Given this, it is vital to explore alternative breast milk preservation methods. Technologies like Holder Pasteurization (HoP), High-Temperature Short-Time Pasteurization (HTST), High-Pressure Processing (HPP), UV radiation (UV), and Electric Pulses (PEF) have been introduced to conserve HBM. This review aims to enhance the understanding of preservation techniques for HBM, supporting the practice of extended exclusive breastfeeding. It explicitly addresses microbial concerns, focusing on critical pathogens like Staphylococcus aureus, Enterococcus, Escherichia coli, Listeria monocytogenes, and Cytomegalovirus, and explores how various preservation methods can mitigate these risks. Additionally, the review highlights the importance of retaining the functional elements of HBM, particularly its immunological components such as antibodies and enzymes like lysozyme and Bile Salt Stimulated Lipase (BSSL). The goal is to provide a comprehensive overview of the current state of HBM treatment, critically assess existing practices, identify areas needing improvement, and advocate for extended exclusive breastfeeding due to its vital role in ensuring optimal nutrition and overall health in infants.

Formulation factors affecting foam properties during vacuum foam-drying

This paper explores how vacuum foam-drying of a protein is influenced by formulation parameters by investigating the foam structure, physical properties of the foam, and the stability of the protein. Recombinant human bile salt-stimulated lipase was used as a model of a protein drug. The stability of the lipase was evaluated through activity measurements. Two disaccharides (sucrose and trehalose), strongly tending to an amorphous form, were used as matrix formers, and the physical properties were assessed through residual water content, glass transition temperature, and crystalline state. Moreover, some formulations included surfactants with different sizes and structures of the head group. The alkyl chain length was kept constant to only investigate the impact of the surfactant head group, in the presence of the lipase, on the foamability and surface coverage of the lipase. The study demonstrated that the lipase allowed for a dry, solid foam with a foam overrun of up to 2600 %. The wall thickness of the dry, solid foam was estimated to be 20–50 µm. Clear differences between sucrose and trehalose as matrix former were identified. The lipase showed no tendency to lose activity because of the drying and rehydration, despite a proportion of the lipase covering the surfaces of the dry material.

The change of bile salt stimulated lipase during 6 months and the correlation with macronutrients in Chinese human milk

Bile salt stimulated lipase (BSSL) is the most abundant lipase in human milk which plays a pivotal role in new-born fat digestion, especially in the first six months of life. Lipid as the main energy supply for infant was very depending on BSSL activity for obtaining optimal lipid absorption under immature digestion track and pancreatic system condition. Due to the important role of BSSL, this research was addressed to study the effect of gender and lactation stage on BSSL activity and the correlation of BSSL with macronutrients content in Chinese human milk. Cross sectional and longitudinal study were used to investigate the BSSL activity and concentration pattern during 6 months of lactation. A declining pattern of both BSSL activity and concentration was observed as lactation stage progressed. The BSSL concentration significantly declined from 138.56 to 97.07 μg/ml during 6 months. Significant differences of BSSL activity and concentration were also observed in human milk for different gender babies. Male babies had breastmilk with less BSSL rather than female babies. Protein had strong correlation with BSSL activity and concentration, while carbohydrate had non-significant negative coefficient correlation. However, no correlation observed between fat content and BSSL.

Effects of bile salt-stimulated lipase on blood cells and associations with disease activity in human inflammatory joint disorders.

The bile salt-stimulated lipase (BSSL) was originally recognized as a lipolytic enzyme expressed by the exocrine pancreas and in some species, notably humans, the lactating mammary gland, being secreted into the duodenum and with the mother's milk, respectively. However, BSSL is also present in the blood and has been assigned additional functions, even beyond the gastrointestinal tract. Conventional BSSL knockout mice are protected from developing disease in animal models of arthritis, and antibodies directed towards BSSL prevent or mitigate disease in similar models. The aim of this study was to investigate the role of BSSL as a newly discovered player in inflammation and specifically in inflammatory joint disorders. As part of mechanism of action, we here show that BSSL is secreted by neutrophils, interacts with monocytes and stimulates their migration in vitro. An anti-BSSL antibody that blocks the human BSSL-monocyte interaction was shown to simultaneously prevent the signaling pathway by which BSSL induce cell migration. Moreover, in this cohort study we show that BSSL levels are significantly higher in blood samples from patients with rheumatoid arthritis and psoriatic arthritis compared to healthy controls. The BSSL levels in patients' blood also correlated with disease activity scores and established inflammatory markers. Hence, although the mode of action is not yet fully clarified, we conclude that BSSL could be considered a proinflammatory component in the innate immune system and thus a possible novel target for treatment of chronic inflammation.

High-Pressure Processing of Human Milk: A Balance between Microbial Inactivation and Bioactive Protein Preservation

BackgroundDonor human milk banks use Holder pasteurization (HoP; 62.5°C, 30 min) to reduce pathogens in donor human milk, but this process damages some bioactive milk proteins. ObjectivesWe aimed to determine minimal parameters for high-pressure processing (HPP) to achieve >5-log reductions of relevant bacteria in human milk and how these parameters affect an array of bioactive proteins. MethodsPooled raw human milk inoculated with relevant pathogens (Enterococcus faecium, Staphylococcus aureus, Listeria monocytogenes, Cronobacter sakazakii) or microbial quality indicators (Bacillus subtilis and Paenibacillus spp. spores) at 7 log CFU/mL was processed at 300–500 MPa at 16–19°C (due to adiabatic heating) for 1–9 min. Surviving microbes were enumerated using standard plate counting methods. For raw milk, and HPP-treated and HoP-treated milk, the immunoreactivity of an array of bioactive proteins was assessed via ELISA and the activity of bile salt-stimulated lipase (BSSL) was determined via a colorimetric substrate assay. ResultsTreatment at 500 MPa for 9 min resulted in >5-log reductions of all vegetative bacteria, but <1-log reduction in B. subtilis and Paenibacillus spores. HoP decreased immunoglobulin A (IgA), immunoglobulin M (IgM), immunoglobulin G, lactoferrin, elastase and polymeric immunoglobulin receptor (PIGR) concentrations, and BSSL activity. The treatment at 500 MPa for 9 min preserved more IgA, IgM, elastase, lactoferrin, PIGR, and BSSL than HoP. HoP and HPP treatments up to 500 MPa for 9 min caused no losses in osteopontin, lysozyme, α-lactalbumin and vascular endothelial growth factor. ConclusionCompared with HoP, HPP at 500 MPa for 9 min provides >5-log reduction of tested vegetative neonatal pathogens with improved retention of IgA, IgM, lactoferrin, elastase, PIGR, and BSSL in human milk.

Adaption of a commercial lipase kit to measure bile salt-stimulated lipase in human milk

A highly sensitive, fluorometric method for measuring activities of two major lipases in milk, lipoprotein lipase (LPL) and bile salt-stimulated lipase (BSSL) is described. Human milk LPL showed linear activity from 65 to 347 U/L (U = 1 μmol/min) and the quantification limit was theoretically about 65 U/L. For human milk BSSL, the linear range was from 10 to 267 U/L and the quantification limit was 18 U/L. The mean LPL and BSSL activities were 409 ± 13 U/L and 5263 ± 132 U/L, respectively. This corresponded well to the values reported in literature. The residual LPL and BSSL activities were reduced dramatically to 21%, and 2%, respectively, when the milk was heated to 55 °C; heating to 50 °C caused only nominal reductions of LPL and BSSL (activities remaining ∼82% and 87%, respectively). No BSSL activity was detected in cow, camel, goat milk or in infant formula.

Effects of High-Pressure Processing, UV-C Irradiation and Thermoultrasonication on Donor Human Milk Safety and Quality.

Holder pasteurization (HoP) is the current recommended treatment for donor human milk. Although this method inactivates microbial contaminants, it also negatively affects various milk components. High-pressure processing (HPP, 400, 500, and 600 MPa), ultraviolet-C irradiation (UV-C, 2,430, 3,645, and 4,863 J/L) and thermoultrasonication (TUS, 1,080 and 1,620 kJ/L) were investigated as alternatives to thermal pasteurization (HoP). We assessed the effects of these methods on microbiological safety, and on concentration and functionality of immunoglobulin A, lactoferrin, lysozyme and bile salt-stimulated lipase, with LC-MS/MS-based proteomics and activity assays. HoP, HPP, TUS, and UV-C at 4863 J/L, achieved >5-log10 microbial reduction. Native protein levels and functionality showed the highest reduction following HoP, while no significant reduction was found after less intense HPP and all UV-C treatments. Immunoglobulin A, lactoferrin, and lysozyme contents were also preserved after low intensity TUS, but bile salt-stimulated lipase activity was significantly reduced. This study demonstrated that HPP and UV-C may be considered as suitable alternatives to HoP, since they were able to ensure sufficient microbial inactivation while at the same time better preserving the bioactive components of donor human milk. In summary, our results provide valuable insights regarding the evaluation and selection of suitable processing methods for donor human milk treatment, which may replace HoP in the future.

High-Temperature Short-Time Preserves Human Milk's Bioactive Proteins and Their Function Better Than Pasteurization Techniques With Long Processing Times.

Donor human milk is generally processed by holder pasteurization (HoP) at 62. 5°C for 30 min. This temperature-time combination is sufficient for eliminating pathogens in donor milk, but also negatively affects several bioactive milk components. Long heating up times may further affect the bioactive properties of pasteurized milk. High-Temperature-Short-Time (HTST), a treatment with shorter processing times (72°C for 15 sec), was investigated as a suitable alternative to HoP. In addition, pasteurization methods that follow the same temperature regime but with varying heating up times were compared. Human milk samples from four different donors were combined into one pool, which was then used to perform all analyses. The effects of these methods on the levels and functionality of immunoglobulin A, lactoferrin, lysozyme and bile salt-stimulated lipase, were evaluated with LC-MS/MS-based proteomics and activity assays, while the pasteurization efficacy was evaluated with an alkaline phosphatase test. HoP, a treatment with long processing times, times, caused the highest reduction in all proteins studied (reduced by 50–98%). Compounds such as lactoferrin and bile salt-stimulated lipase that are more sensitive to heat treatments were better retained with HTST, but their levels and functionality were still significantly lower than those of untreated donor milk (52 and 81% reduction of lactoferrin and bile salt-stimulated lipase activity, respectively). Our findings showed that a treatment with considerably shorter processing times, such as HTST, may reduce the thermal damage caused to the bioactive proteins compared to HoP, without affecting pasteurization efficacy. Since the vast majority of the donor human milk banks that are currently operating on a global level apply HoP to donor milk, our findings may provide relevant information for the optimization of donor milk processing.

Adaption of a Commercial Lipase Kit to Measure Bile Salt-Stimulated Lipase in Human Milk

Adaption of a Commercial Lipase Kit to Measure Bile Salt-Stimulated Lipase in Human Milk

Comparing the effects of hydrostatic high-pressure processing vs holder pasteurisation on the microbial, biochemical and digestion properties of donor human milk

In this study, hydrostatic high-pressure processing (HHP), a non-thermal pasteurisation method, was used to achieve the microbiological safety of donor human milk. After HHP, no bacteria were detected in human milk processed at 400 MPa for 5 min. Activities of a selection of bioactive components, including lysozyme, xanthine oxidase, lactoperoxidase, immunoglobulin A, lactoferrin, lipoprotein lipase and bile salt-stimulated lipase, did not decrease significantly. This study further investigated the gastrointestinal digestion kinetics of HoP and HHP milk compared with raw human milk, using an in vitro static infant digestion model. After 60 min of ‘gastric digestion’, the microstructure and protein profile of HHP milk samples were more similar to raw milk samples than HoP milk samples. Overall, HPP showed a better retention in milk nutrients and closer digestion behavior than that of HoP.

Evaluation of protein: lipid ratio on growth, feed efficiency, and metabolic response in juvenile yellowtail snapper Ocyurus chrysurus (Bloch, 1791)

This study was conducted to evaluate juveniles' Ocyurus chrysurus (13.7 ± 0.45 g initial weight) to utilize lipid as an energy source on growth, feed efficiency, body composition, digestive and hepatic enzyme activities. Four diets of two protein levels (40 and 50%) with two lipid levels (6 and 12%) and 2% of digestible carbohydrates were formulated. Fish were fed for 60 days to apparent satiation at a stocking density of 10 fish per tank (100 L). Growth gain of fish fed 50% dietary protein was higher than of fish fed 40% dietary protein (P &lt; 0.05). However, feed efficiency was significantly higher at 12 than 6% of dietary lipid. Whole-body lipid and glycogen in the liver increased dramatically with dietary lipid content-alkaline protease activity trend increased as dietary protein increased. Trypsin activity increased significantly as dietary lipid decreased, whereas chymotrypsin activity showed the opposite trend (P &lt; 0.05). Bile salt-dependent lipase activity trend towards increasing as dietary energy decreased. Glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), and fructose-1, 6-biphosphatase (FBPase) significantly increased with increasing dietary lipid levels. However, alanine aminotransferase (ALT) activity increased with dietary protein content. On the other side, pyruvate kinase (PK) activity increased with both dietary protein and lipid content. This study indicates that high dietary lipid (12%) improved the feed efficiency but did not reduce dietary protein demand in juveniles O. chrysurus.

Lipid Composition, Digestion, and Absorption Differences among Neonatal Feeding Strategies: Potential Implications for Intestinal Inflammation in Preterm Infants.

Necrotizing enterocolitis (NEC) is a significant cause of morbidity and mortality in the neonatal population. Formula feeding is among the many risk factors for developing the condition, a practice often required in the cohort most often afflicted with NEC, preterm infants. While the virtues of many bioactive components of breast milk have been extolled, the ability to digest and assimilate the nutritional components of breast milk is often overlooked. The structure of formula differs from that of breast milk, both in lipid composition and chemical configuration. In addition, formula lacks a critical digestive enzyme produced by the mammary gland, bile salt-stimulated lipase (BSSL). The gastrointestinal system of premature infants is often incapable of secreting sufficient pancreatic enzymes for fat digestion, and pasteurization of donor milk (DM) has been shown to inactivate BSSL, among other important compounds. Incompletely digested lipids may oxidize and accumulate in the distal gut. These lipid fragments are thought to induce intestinal inflammation in the neonate, potentially hastening the development of diseases such as NEC. In this review, differences in breast milk, pasteurized DM, and formula lipids are highlighted, with a focus on the ability of those lipids to be digested and subsequently absorbed by neonates, especially those born prematurely and at risk for NEC.

High-Temperature Short-Time and Holder Pasteurization of Donor Milk: Impact on Milk Composition.

Holder pasteurization (HoP; 62.5 °C, 30 min) is commonly used to ensure the microbiological safety of donor human milk (DHM) but diminishes its nutritional properties. A high-temperature short-time (HTST) system was designed as an alternative for human milk banks. The objective of this study was to evaluate the effect of this HTST system on different nutrients and the bile salt stimulated lipase (BSSL) activity of DHM. DHM was processed in the HTST system and by standard HoP. Macronutrients were measured with a mid-infrared analyzer. Lactose, glucose, myo-inositol, vitamins and lipids were assayed using chromatographic techniques. BSSL activity was determined using a kit. The duration of HTST treatment had a greater influence on the nutrient composition of DHM than did the tested temperature. The lactose concentration and the percentage of phospholipids and PUFAs were higher in HTST-treated than in raw DHM, while the fat concentration and the percentage of monoacylglycerides and SFAs were lower. Other nutrients did not change after HTST processing. The retained BSSL activity was higher after short HTST treatment than that following HoP. Overall, HTST treatment resulted in better preservation of the nutritional quality of DHM than HoP because relevant thermosensitive components (phospholipids, PUFAs, and BSSL) were less affected.

Longitudinal changes in the bioactive proteins in human milk of the Chinese population: A systematic review.

This systematic review aimed at investigating longitudinal changes in human milk bioactive protein concentrations in Chinese population. Both English and Chinese databases were searched. The data were pooled into six defined lactation stages. Weighted means of protein concentrations in each stage and the statistical significance of means of different lactation stages were calculated. The data of 11 bioactive proteins were retrieved. Concentrations of sIgA, IgM, and IgG decreased sharply during the first 14 days of lactation. The levels of α‐lactalbumin, lactoferrin, and β‐casein also decreased throughout lactation. Conversely, lysozyme levels increased over lactation. The changing patterns of the serum albumin, osteopontin, and bile salt‐stimulated lipase (BSSL) were not conclusive. This study represents the most comprehensive summary of bioactive proteins in Chinese human milk. In the future, mass spectrometry‐based analysis of human milk proteomics may be used to investigate the longitudinal changes of many more bioactive proteins.

Bile salt-dependent lipase promotes the barrier integrity of Caco-2 cells by activating Wnt/β-catenin signaling via LRP6 receptor.

Bile salt-dependent lipase (BSDL) within intestinal lumen can be endocytosed by enterocytes and support the intestinal barrier function. However, the epithelial-supporting effect of this protein has not been verified in a human cell line and neither the direct signaling pathway nor the function of endocytosis in this process has been clearly identified. We sought to investigate the signaling pathway and the membrane receptor through which BSDL might exert these effects using intestinal epithelial cells. Caco-2 cells were treated with recombinant BSDL, and the barrier function, cell proliferation, and activation of the Wnt signaling pathway were assessed. The effect of Wnt signaling activation induced by BSDL and BSDL endocytosis was investigated in LRP6-silenced and non-silenced cells. Moreover, caveolae- and clathrin-dependent endocytosis inhibitors were also applied respectively to analyze their effects on Wnt signaling activation induced by BSDL. BSDL treatment increased the barrier function but not proliferation of Caco-2 cells. It also induced β-catenin nuclear translocation and activated Wnt target gene transcription. Moreover, in the Wnt pathway, BSDL increased the levels of non-phosphorylated-β-catenin (Ser33/37/Thr41) and phosphorylated-β-catenin (Ser552). Notably, the silencing of LRP6 expression impaired BSDL endocytosis and decreased BSDL-induced β-catenin nuclear translocation. The inhibition of BSDL endocytosis induced by caveolae-mediated endocytosis inhibitor was stronger than that by clathrin-mediated endocytosis inhibitor, and the Wnt signaling activation associated with its endocytosis was also most likely caveolae-dependent. Our findings suggested that LRP6, a canonical Wnt pathway co-receptor, can mediate BSDL endocytosis and then activate Wnt signaling in Caco-2 cells.

Bile Salt-Stimulated Lipase Activity in Donor Breast Milk Influenced by Pasteurization Techniques.

Breast milk contains bile salt-stimulated lipase (BSSL), which significantly increases the fat digestion capacity of newborns who have limited pancreatic lipase secretion in the first few months after birth. Problematically, Holder pasteurization used in non-profit milk banks to ensure the microbiological safety of donor milk for infants, particularly preterm infants (<37 weeks gestation age), destroys milk BSSL, thus limiting infant fat absorption capacity. Alternative strategies are needed to ensure the safety of donor milk while preserving BSSL activity. Three alternative pasteurization techniques—high-pressure processing (HPP, 550 MPa, 5 min), gamma cell irradiation (IR, 2.5 Mrads) and UV-C (254 nm, 0–33,000 J/L)—were compared with Holder pasteurization (low-temperature long-time, LTLT, 62.5°C, 30 min) for retention of BSSL activity in donor breast milk. As the time required for donor milk pasteurization by UV-C in published methods was not clear, donor breast milk was spiked with seven common bacterial strains and treated by UV-C for variable time periods and the minimum UV-C dosage required to achieve a 5-log10 reduction of CFU/mL was determined. Eight thousand two hundred fifty J/L of UV-C exposure was sufficient to achieve 5-log10 reduction of each of bacterial targets, including Bacillus and Paenibacillus spores. The retention of BSSL activity was highest after HPP (retaining 62% of the untreated milk BSSL activity), followed by UV-C (16,500 J/L), IR and LTLT (35, 29, and 0.3% retention, respectively). HPP was an effective alternative to pasteurize milk with improved retention of BSSL activity compared to Holder pasteurization. Future work should investigate the effect of alternative pasteurization techniques on the entire array of bioactive components in donor breast milk and how these changes affect preterm infant health outcomes. Implementation of HPP technique at milk banks could improve donor milk-fed infant fat absorption and growth.

Bile-salt stimulated lipase polymorphisms do not associate with HCV susceptibility

Bile-salt stimulate lipase (BSSL) is a glycoprotein found in human milk and blood that can potently bind DC-SIGN. The BSSL gene is highly polymorphic with a variant number of O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene. It has been shown that certain BSSL genotypes associate with decreased HIV-1 transmission in vitro and decreased HIV-1 disease progression. The protein forms dimers and individuals possessing one high (typically 14–21) and one low (typically 7–11) number of repeat domains has been shown to have stronger binding of BSSL to DC-SIGN and HIV-1 inhibitory activity in vitro. Since we previously demonstrated that SNPs within the DC-SIGN gene can associate with risk of HCV sexual transmission and which can be linked to diminished DC-SIGN gene expression we aimed to identify whether BSSL polymorphisms associated similarly through differential binding to DC-SIGN. DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU). The numbers of repeats in exon 11 were determined by PCR with repeat distributions compared between MEI and MEU. No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the BSSL gene was observed when comparing HCV infected MEI with MEU, thus the exon 11 repeat copy number in the BSSL gene does not affect HCV susceptibility.

A new prognostic factor of breast cancer: High carboxyl ester lipase expression related to poor survival

ObjectiveThe enzyme carboxyl ester lipase (CEL), known as bile salt-dependent lipase (BSDL) or bile salt-stimulated lipase (BSSL), is mainly expressed in pancreatic acinar cells and lactating mammary glands. To investigate the link between CEL expression of breast cancer (BC) tissues and the survival of BC patients by analyzing The Cancer Genome Atlas Breast Carcinoma (TCGA-BRCA) level 3 data. MethodsThe clinical information and RNA-sequencing (RNA-Seq) expression data were downloaded from TCGA. Patients were divided into a high CEL expression group and a low CEL expression group using the optimal cutoff value (5.611) identified from the ROC curve. Chi-square test and Fisher exact test were used to find the correlation between the expression of CEL and clinicopathologic features. To assess the diagnostic capability, the receiver operating characteristic (ROC) curve of CEL was drawn. The survival differences between high and low CEL expression groups were compared by Cox regression analysis. Log-rank test was applied to the calculation of p values and the comparison of the Kaplan–Meier curves. Furthermore, Gene Expression Omnibus (GEO) datasets were used for external data validation. ResultsAnalysis of 1104 cases of tumor data showed that CEL was over-expressed in breast cancer. There were relationships between high CEL expression and clinicopathologic features. The high CEL expression group had a lower survival. By analyzing the area under the ROC curve (AUC) of CEL, it was found to have a limited diagnostic capability. CEL expression may be an independent prognostic factor for breast cancer survival through the multivariate analysis. The validation in GEO datasets also showed that CEL expression was higher in breast tumor tissues than in normal breast tissues. High CEL expression was associated with the poor overall survival of breast cancer. ConclusionsHigh CEL expression may be an independent prognostic factor for the poor survival of breast cancer.