Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment

Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

Action of ANG II and ANP on colon epithelial cells

The interaction of angiotensin II (ANG II) and atrial natriuretic peptide (ANP) on intracellular pH (pH_i) and calcium ([Ca²⁺]_i) was investigated in T84 cells (a permanent cell line derived from human colon epithelium) using the fluorescent stains BCECF/AM and Fluo 4/AM, respectively. pH_i recovery rate mediated by the Na⁺/H⁺ exchanger (NHE) was examined following an NH₄Cl pulse. Under control conditions pH_i recovered at 0.114±0.005 pH units/min (n=35). ANG II (10^–12 or 10^–9 M) increased this value, whilst ANG II (10^–7 M) decreased it. These effects of ANG II were impaired by simultaneous addition of 1 M or 25 M HOE-694, indicating that the stimulatory and inhibitory effects of ANG II on pH_i recovery are mediated in part via the NHE1 and NHE2 isoforms. ANG II increased [Ca²⁺]_i concentration-dependently. ANP (10^–6 M) or dimethyl-BAPTA/AM (50 M) blocked the effects of ANG II on [Ca²⁺]_i and on the rate of pH_i recovery. Thapsigargin (10^–5 M) enhanced the effect of ANG II on [Ca²⁺]_i and reversed its stimulatory effect on the rate of pH_i recovery to an inhibitory one. External Ca²⁺-free solution did not affect the effects of ANG II on these parameters. These data suggest that the [Ca²⁺]_i increase induced by ANG II is dependent on intracellular calcium stores. They are compatible with the demonstration of two sites on the C-terminal of the Na⁺/H⁺ exchanger, one stimulating Na⁺/H⁺ activity by increases of [Ca²⁺]_i in the lower range (at 10^–12 or 10^–9 M ANG II) and the other inhibiting this activity at high [Ca²⁺]_i levels (at 10^–7 M ANG II). ANP or dimethyl-BAPTA/AM, by impairing the pathway mediating the increase in [Ca²⁺]_i, block both the stimulatory and inhibitory effects of ANG II.     

Distinct Leishmania braziliensis isolates induce different paces of chemokine expression patterns

Inflammatory events during Leishmania braziliensis infection in mice were investigated. Large lesions were directly correlated with the inflammatory reaction but not with parasite burden. Different L. braziliensis strains induce different paces of chemokine expression patterns, leading to diverse cell recruitment and differential inflammatory responses.     

Does Flavonoid Consumption Improve Exercise Performance? Is It Related to Changes in the Immune System and Inflammatory Biomarkers? A Systematic Review of Clinical Studies since 2005

Flavonoids are attracting increasing attention due to their antioxidant, cardioprotective, and immunomodulatory properties. Nevertheless, little is known about their role in exercise performance in association with immune function. This systematic review firstly aimed to shed light on the ergogenic potential of flavonoids. A search strategy was run using SCOPUS database. The returned studies were screened by prespecified eligibility criteria, including intervention lasting at least one week and performance objectively quantified, among others. Fifty-one studies (54 articles) met the inclusion criteria, involving 1288 human subjects, either physically untrained or trained. Secondly, we aimed to associate these studies with the immune system status. Seventeen of the selected studies (18 articles) assessed changes in the immune system. The overall percentage of studies reporting an improved exercise performance following flavonoid supplementation was 37%, the proportion being 25% when considering quercetin, 28% for flavanol-enriched extracts, and 54% for anthocyanins-enriched extracts. From the studies reporting an enhanced performance, only two, using anthocyanin supplements, focused on the immune system and found certain anti-inflammatory effects of these flavonoids. These results suggest that flavonoids, especially anthocyanins, may exert beneficial effects for athletes’ performances, although further studies are encouraged to establish the optimal dosage and to clarify their impact on immune status.     

Immunophenotypic and DNA content characteristics of plasma cells in multiple myeloma and monoclonal gammopathy of undetermined significance

In the present paper we review the immunophenotypic characteristics of plasma cells (PC) and the PC DNA contents from multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS), and its value for the differential diagnosis between both entities. The strong reactivity for CD38 and the positivity for CD138 are the two best markers for identifying PC. Myelomatous PC display an heterogeneous phenotype consistent with the fact that the neoplastic clone is able to undergo a certain degree of differentiation. In addition, PC from MM patients usually lack surface expression of B-cell associated antigens and frequently display reactivity for markers which are not restricted to the B-cell lineage. In MGUS patients, two clearly defined and distinct PC subpopulations can be identified. One of these PC subpopulations shows phenotypic characteristics identical to those of normal PC, including a very strong reactivity for the CD38 antigen, intermediate/low light scatter characteristics and positivity for CD19, in the absence of CD56, and corresponds to the residual normal bone marrow PC. The second PC subpopulation shows an immunophenotype similar to that of myelomatous PC, characterized by a slightly lower reactivity for CD38 and strong CD56 expression, on the absence of positivity for CD19, these PC corresponding to the clonal counterpart. Using a simultaneous staining for PC and DNA, around 60% of MM and 73% of MGUS patients display DNA aneuploidy, the majority of them being hyperdiploid. However, in contrast to MM patients, in MGUS patients two clearly different PC subsets can be discriminated in most cases (73%): a diploid and an aneuploid (hyperdiploid) subset, corresponding to normal and clonal PC, respectively. Upon comparing hyperdiploid with diploid patients in MM, the former display a better prognosis, in line with the higher incidence of DNA hyperdiploidy in MGUS. A clear correlation between the percentage of S-phase PC and several prognosis features of MM has been found. In spite of these findings, no significant differences in the percentage of pathological S-phase PC are detected between MM and MGUS patients. Regarding the differential diagnosis between MGUS and MM, multivariate analysis shows that the ratio between the number of clonal and normal residual PC is the best single parameter.     

Population study of Aymara Amerindians for the PCR-DNA polymorphisms HUMTH01, HUMVWA31A, D3S1358, D8S1179, D18S51, D19S253, YNZ22 and HLA-DQα

Allele and genotype frequencies for eight DNA polymorphisms (HUMTH01, HUMVWA31A, D3S1358, D8S1179, D18S51, D19S253, YNZ22 and HLA-DQalpha) were determined in a population sample of Aymara Indians from Bolivia using PCR. No deviations of the observed allelic frequencies from Hardy-Weinberg equilibrium were found for all the systems studied. Significant differences in the allele frequencies were found between the Aymara and Quechua populations only for HUMVWA31A, which suggests a certain degree of genetic differentiation between the two populations.     

Revisiting colorectal cancer animal model – An improved metastatic model for distal rectosigmoid colon carcinoma

Colorectal cancer (CRC) is the second most frequent and fatal cancer in Western countries. Understanding its biology with different incidence along the colon and rectum, genetic profile and how these factors contribute to local/distant progression, has been hampered by the lack of a suitable CRC model.We report a reproducible model, using human CRC cell lines (CL) (WiDr, LS1034, C2BBe1) injected (1?×?10⁷ cells/animal) in RNU rats (n?=?55) which underwent cecostomy and descending colostomy with mucosal-cutaneous fistula of the sigmoid colon. CL were characterized by immunohistochemistry: CK20, CDX2, P53, vimentin, Ki67, CD44, CD133, E-cadherin, β-catenin and CEA; cancer stem cells-immune system interaction was studied and tumor progression was assessed with nuclear medicine imaging (^99mTc-MIBI).Animals developed locally invasive tumors and with WiDr neural invasion was registered. Cancer stem cells were detected in WiDr (CD44 positive). All the cell lines stimulated the immune system, being WiDr the most aggressive. Imaging studies demonstrated tumor uptake.With this CRC model we can study the microenvironment role and tumor-stroma interactions. All CL developed primary disease, but only the WiDR established neural invasion which may represent a metastatic pathway. This model can help unveiling the underlying metastatic mechanisms, and ultimately test better therapeutic approaches for CRC.