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Postpartum depression affects a huge number of women and has detrimental consequences. Knowing the factors associated with postpartum depression during pregnancy can help its prevention. Although there is evidence surrounding behavioral or psychological predictors of postpartum depression, there is a lack of evidence of biological forecasters. The aim of this study was to analyze the sociodemographic, obstetric, and psychological variables along with hair cortisol levels during the first, second, and third trimesters of pregnancy that could predict postpartum depression symptoms. A sample of 44 pregnant women was assessed during 3 trimesters of pregnancy and the postpartum period using psychological questionnaires and hair cortisol levels. Participants were divided into 2 groups: a group with postpartum depression symptoms and a group with no postpartum depression symptoms. Results showed significant positive differences between groups in the first trimester regarding the Somatization subscale of the SCL-90-R (p < .05). In the second trimester, significant differences were found in the Somatization, Depression, Anxiety, and GSI subscales (p < .05). In the third trimester significant differences between both groups were found regarding pregnancy-specific stress. We found significant positive differences between groups regarding hair cortisol levels in the first and the third trimester. Hair cortisol levels could predict 21.7% of the variance of postpartum depression symptoms. In conclusion, our study provided evidence that psychopathological symptoms, pregnancy-specific stress, and hair cortisol levels can predict postpartum depression symptoms at different time-points during pregnancy. These findings can be applied in future studies and improve maternal care in clinical settings.

Treatment with glucocorticoids (GCs) may cause adverse effects, including cholestasis. The ability of dexamethasone, prednisolone and budesonide to affect the liver handling of bile acids (BAs) has been investigated. In rats treated with GCs for 4 days, altered serum and bile BA levels, changed conjugation pattern, and delayed and decreased ability to conjugate/secrete exogenously administered deoxycholate, were found using HPLC-MS/MS. RT-QPCR analyses revealed that GC treatment also induced a down-regulation of liver nuclear receptors (Fxr, Gr and Shp), transporters (Ntcp, Mrp4 and Bcrp) and enzymes (Cyp7a1 and Baat), whereas Bsep, Mrp2 and Cyp27a1 were up-regulated. Human HepG2 and Alexander cell lines were used as in vitro models of liver cells with and without constitutive FXR expression, respectively. In HepG2 cells, GCs induced a decreased expression of FXR and SHP, and inhibited the regulatory effect of GW4064 on FXR-target genes. In Alexander cells, only when they were transfected with FXR+RXR, GW4064 caused up-regulation of SHP and OSTβ, and a down-regulation of CYP27A1. GCs had the opposite effect on these genes, both in the absence and in the presence of FXR expression. Co-transfection of Alexander cells with IR-1-Luc and FXR+RXR revealed that GCs did not inhibit but moderately enhanced FXR activity. Moreover, GCs have a synergistic effect on GW4064-induced FXR activation, whereas chenodeoxycholate and GW4064 have an additive effect. In conclusion, GCs are able to directly or indirectly activate FXR but they also antagonize, through FXR-independent mechanisms, the expression of FXR and FXR target genes involved in the hepatic handling of BAs., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in industrialized countries. Chemoprevention is a promising approach, but studies demonstrating their usefulness in large populations are still needed. Among several compounds with chemopreventive ability, cyclooxygenase inhibitors have received particular attention. However, these agents are not without side effects, which must be weighed against their beneficial actions. Early diagnosis is critical in the management of CRC patients, because, in early stages, surgery is curative in >90% of cases. If diagnosis occurs at stages II and III, which is often the case, neoadjuvant chemotherapy and radiotherapy before surgery are, in a few cases, recommended. Because of the high risk of recurrence in advanced cancers, chemotherapy is maintained after tumor resection. Chemotherapy is also indicated when the patient has metastases and in advanced cancer located in the rectum. In the last decade, the use of anticancer drugs in monotherapy or in combined regimens has markedly increased the survival of patients with CRC at stages III and IV. Although the rate of success is higher than in other gastrointestinal tumors, adverse effects and development of chemoresistance are important limitations to pharmacological therapy. Genetic profiling regarding mechanisms of chemoresistance are needed to carry out individualized prediction of the lack of effectiveness of pharmacological regimens. This would minimize side effects and prevent the selection of aggressive, cross-resistant clones, as well as avoiding undesirable delays in the use of the most efficient therapeutic approaches to treat these patients.

Bile acids (BAs) have a long established role in fat digestion in the intestine by acting as tensioactives, due to their amphipatic characteristics. BAs are reabsorbed very efficiently by the intestinal epithelium and recycled back to the liver via transport mechanisms that have been largely elucidated. The transport and synthesis of BAs are tightly regulated in part by specific plasma membrane receptors and nuclear receptors. In addition to their primary effect, BAs have been claimed to play a role in gastrointestinal cancer, intestinal inflammation and intestinal ionic transport. BAs are not equivalent in any of these biological activities, and structural requirements have been generally identified. In particular, some BAs may be useful for cancer chemoprevention and perhaps in inflammatory bowel disease, although further research is necessary in this field. This review covers the most recent developments in these aspects of BA intestinal biology.

Background & Aims: Dietary fiber has been proven to be beneficial in maintaining remission in human ulcerative colitis, an effect related with an increased luminal production of short-chain fatty acids (SCFA). The aim of the present study was to further investigate the mechanisms involved in the intestinal anti-inflammatory effects of dietary fiber in an experimental model of rat colitis., Methods: HLA-B27 transgenic rats (8-10 weeks old) were fed a fiber-supplemented diet (5% Plantago ovata seeds) for 13 weeks before evaluation of the colonic inflammatory status, both histologically and biochemically. The luminal colonic production of SCFA was quantified. In vitro studies were also performed to test the interaction between two SCFA (butyrate and propionate) as inhibitors of cytokine production in THP-1 cells., Results: Dietary fiber supplementation ameliorated the development of colonic inflammation in transgenic rats as evidenced by an improvement of intestinal cytoarchitecture. This effect was associated with a decrease in some of the pro-inflammatory mediators involved in the inflammatory process: nitric oxide, leukotriene B(4), tumor necrosis factor alpha (TNFalpha). The intestinal contents from fiber-treated colitic rats showed a significant higher production of SCFA, butyrate and propionate, than non-treated colitic animals. In vitro studies revealed a synergistic inhibitory effect of butyrate and propionate on TNFalpha production., Conclusions: Dietary fiber supplementation ameliorated colonic damage in HLA-B27 transgenic rats. This effects was associated with an increased production of SCFA, which can act synergistically in inhibiting the production of pro-inflammatory mediators.

A systematic study was conducted on the requirements at the C-terminal position for the targeting of LAMPs to lysosomes, examining the hypothesis that a bulky hydrophobic residue is required. Mutations deleting or replacing the C-terminal valine with G, A, C, L, I, M, K, F, Y, or W were constructed in a reporter protein consisting of the lumenal/extracellular domain of avian LAMP-1 fused to the transmembrane and cytoplasmic domains of LAMP-2b. The steady-state distribution of each mutant form in mouse L-cells was assessed by quantitative antibody binding assays and immunofluorescence microscopy; efficiency of internalization from the plasma membrane and delivery to the lysosome were also estimated. It is found that (a) only C-terminal V, L, I, M, and F mediated efficient targeting to lysosomes, demonstrating the importance hydrophobicity and an optimal size of the C-terminal residue in targeting; (b) efficiency of lysosomal targeting generally correlated with efficiency of internalization; and (c) mutant forms that did not target well to lysosomes showed unique distributions in cells rather than simply default accumulation in the plasma membrane. Interactions of the targeting signals with adaptor subunits were measured using a yeast two-hybrid assay. The results are consistent with the hypothesis that trafficking of LAMP forms in cells through the indirect pathway is determined by the affinities of their targeting signals, predominantly for the mu2 and mu3 adaptors involved at plasma membrane and endosomal cellular sorting sites, respectively.

The turnover of intestinal epithelial cells is a finely regulated process extending from undifferentiated crypt stem cells to terminally differentiated villus cells. The final phase of this maturation process is apoptosis and extrusion. Recent studies have shown that programmed cell death (PCD) occurs not only in senescent cells and in rapidly developing tissues but also in response to cellular stress preventing damaged cells from entering uncontrolled proliferation without repair. This study examined the role of exogenous nucleotides on cell proliferation, differentiation and apoptosis in organ cultures of human fetal small intestine. The addition of adenosine monophosphate (AMP), a putative stress reactant, to the culture media resulted in the suppression of crypt cell proliferation followed by the restoration of differentiation and the induction of apoptosis across a broad range of villus epithelium when compared with controls without added nucleotide. In contrast, the addition to cytidine monophosphate (CMP) to the culture media did not increase apoptosis, despite the nucleotide being taken up by the fetal small intestine in a similar dose- and time-dependent manner to AMP. Furthermore, Bax mRNA, an apoptosis-inducer gene, was increased with addition of AMP, suggesting that the induction of apoptosis may be channeled through the p53 pathway. These results suggest that a specific exogenous nucleotide, AMP, may have an important role in controlling the dynamic balance of cellular turnover in the developing human small intestine.

The aim of this study was to evaluate the effect of the molecular form of dietary protein (native or enzymatically hydrolyzed) on the total serum protein concentrations and the serum amino acid profile of growing rats at weaning. Wistar male rats at weaning were randomly assigned to one of the four isocaloric and isonitrogenous (12% protein equivalent content) diets and fed for 7 days. The protein sources of the diets were: whey protein, casein and their respective hydrolysates. Differences in the serum amino acid profiles exclusively related to the amino acid composition of the protein (casein or whey proteins) were observed, but differences due to their molecular form were not observed. It is concluded that the use of enzymatic hydrolysates of whey proteins and casein has the same effects as their native proteins on nitrogen intake, body weight gain and serum amino acid profile of growing rats at weaning.