A review of bioactive factors in human breastmilk: A focus on prematurity

Preterm birth is an increasing worldwide problem. Prematurity is the second most common cause of death in children under 5 years of age. It is associated with a higher risk of several pathologies in the perinatal period and adulthood. Maternal milk, a complex fluid with several bioactive factors, is the best option for the newborn. Its dynamic composition is influenced by diverse factors such as maternal age, lactation period, and health status. The aim of the present review is to summarize the current knowledge regarding some bioactive factors present in breastmilk, namely antioxidants, growth factors, adipokines, and cytokines, paying specific attention to prematurity. The revised literature reveals that the highest levels of these bioactive factors are found in the colostrum and they decrease along the lactation period; bioactive factors are found in higher levels in preterm as compared to full-term milk, they are lacking in formula milk, and decreased in donated milk. However, there are still some gaps and inconclusive data, and further research in this field is needed. Given the fact that many preterm mothers are unable to complete breastfeeding, new information could be important to develop infant supplements that best match preterm human milkThis work was supported by Ministerio de Economia y Competitividad (grant number FEM2015-63631-R) to SMA and the Ministerio de Ciencia, Innovación y Universidades (Spain) (grant number RTI2018-097504-B-100) to SMA and MAM-C. Both grants were co-financed with FEDER fund

Strong HIV-1-Specific T Cell Responses in HIV-1-Exposed Uninfected Infants and Neonates Revealed after Regulatory T Cell Removal

BACKGROUND: In utero transmission of HIV-1 occurs on average in only 3%–15% of HIV-1-exposed neonates born to mothers not on antiretroviral drug therapy. Thus, despite potential exposure, the majority of infants remain uninfected. Weak HIV-1-specific T-cell responses have been detected in children exposed to HIV-1, and potentially contribute to protection against infection. We, and others, have recently shown that the removal of CD4(+)CD25(+) T-regulatory (Treg) cells can reveal strong HIV-1 specific T-cell responses in some HIV-1 infected adults. Here, we hypothesized that Treg cells could suppress HIV-1-specific immune responses in young children. METHODOLOGY/PRINCIPAL FINDINGS: We studied two cohorts of children. The first group included HIV-1-exposed-uninfected (EU) as well as unexposed (UNEX) neonates. The second group comprised HIV-1-infected and HIV-1-EU children. We quantified the frequency of Treg cells, T-cell activation, and cell-mediated immune responses. We detected high levels of CD4(+)CD25(+)CD127(−) Treg cells and low levels of CD4(+) and CD8(+) T cell activation in the cord blood of the EU neonates. We observed HIV-1-specific T cell immune responses in all of the children exposed to the virus. These T-cell responses were not seen in the cord blood of control HIV-1 unexposed neonates. Moreover, the depletion of CD4(+)CD25(+) Treg cells from the cord blood of EU newborns strikingly augmented both CD4(+) and CD8(+) HIV-1-specific immune responses. CONCLUSIONS/SIGNIFICANCE: This study provides new evidence that EU infants can mount strong HIV-1-specific T cell responses, and that in utero CD4(+)CD25(+) T-regulatory cells may be contributing to the lack of vertical transmission by reducing T cell activation

Étude de la reconstitution du système immunitaire chez des patients VIH+ traités avec la trithérapie

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Edge enhancement by unsharp masking using liquid-crystal displays

In response to inflammatory stimuli, monocytes/macrophages secrete greater quantities of the proinflammatory cytokines tumour necrosis factor-? (TNF-?), interleukin-1? (IL-1?) and IL-6. The inflammatory process and the innate immune response are related to the activation of several transcription factors, such as nuclear factor ?B (NF-?B) and activator protein 1 (AP-1). The proteasome is a multimeric protease complex, which plays a vital role in several cellular functions, including the regulation of transcription factors like NF-?B. In this study, we used the human monocyte cell line U937 stimulated with lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA) as a model to investigate the in vitro effects of MG132, a proteasome inhibitor, on the release of TNF-?, IL-1? and IL-6 and on the expression of their membrane and soluble receptors TNF-R1, IL-1R1 and IL-6R. We also analysed the effects of MG132 on the activation of NF-?B and AP-1 and on the I?B molecule. MG132 significantly inhibited the secretion of those proinflammatory cytokines. MG132 increased the release of the soluble receptors TNF-R1 and IL-1R1 from U937 cells and decreased their cell-surface expression. MG132 also increased IL-6R cell-surface expression and decreased its release. Proteasome inhibition also led to an increase in LPS+PMA-induced AP-1 activation and the attenuation of LPS+PMA-induced I?B degradation, resulting in the abolition of NF-?B activation. Our experiments strongly suggest that the proteasome is an important factor in the regulation of proinflammatory cytokines and their receptors. " 2008 The Authors.",,,,,,"10.1111/j.1365-2567.2008.02806.x",,,"http://hdl.handle.net/20.500.12104/42800","http://www.scopus.com/inward/record.url?eid=2-s2.0-46949096956&partnerID=40&md5=d605238ef285444652c1dc29f53039f2",,,,,,"4",,"Immunology",,"53

γ-irradiation induced apoptosis in peritoneal macrophages by oxidative stress. Implications of antioxidants in caspase mitochondrial pathway

The in vivo and in vitro development of apoptosis induced by γ-irradiation was studied in mouse peritoneal macrophages. The apoptosis index was measured by fluorescence microscopy and DNA electrophoresis. In vivo apoptosis was greatest eight days after 8 Gy total body γ-irradiation. A DNA ladder electrophoretic pattern was only observed in the γ-irradiated group. The participation of reactive oxygen species in apoptosis induction was investigated by pretreating mice with the antioxidants superoxide dismutase, catalase, vitamin E or lipopolysaccharide before γ-irradiation. Measurement of serum lipoperoxides showed oxidative stress in the γ-irradiated mice and the protection given by the antioxidants. These results were confirmed using in vitro cultures of peritoneal macrophages: γ-irradiated groups and antioxidant-pretreated γ-irradiation groups showed results similar to those observed with in vivo irradiation. A loss of mitochondrial membrane potential (Δψm) was also observed by microscopy in the γ-irradiated cell cultures. Experiments with caspase inhibitors confirmed the participation of caspase 3 and caspase 9

In vivo Adriamycin-induced apoptosis in peritoneal murine macrophages: Partial participation of a caspase cascade

Background: Adriamycin (ADM) is a potent antitumor drug that induces apoptosis (AP) in tumor cells. AP is modulated by caspases and by mitogen-activated protein kinases (MAPK) as well as by the mitochondrial membrane potential (??m). We studied the participation of these systems in peritoneal macrophages from ADM-treated mice. Materials and Methods: Balb/c mice were either treated with ADM (5mg/kg, i.p.) or with 0.85% NaCl solution (controls). One hour later, peritoneal cells were harvested and cultured for 28 h. AP was evaluated by ethidium bromide and acridine orange staining; im was monitored using a MitoCapture stain Kit; DNA integrity was assessed by electrophoretic analysis. Animals were treated (i.p.) 1 h before ADM administration with Z-LEHD-FMK, Z-DEVD-FMK, or Z-VAD-FMK (caspase-9, caspases-3,7,10 and general caspase inhibitors, respectively) or with PD169316 (a MAPK p38 inhibitor). Results: ADM induced a higher rate of AP and the characteristic electrophoretic DNA ladder pattern. Mice treated with caspases inhibitors plus ADM showed significant reductions in AP and DNA laddering; in contrast, no differences were observed in mice treated with PD169316 plus ADM in comparison with ADM alone. ADM also induced early loss of the ??m. Conclusion: In these experimental conditions, ADM induced AP in a mainly caspase-9-dependent manner and this was related to a reduction in the ??m

In vivo Adriamycin-induced apoptosis in peritoneal murine macrophages: Partial participation of a caspase cascade

Background: Adriamycin (ADM) is a potent antitumor drug that induces apoptosis (AP) in tumor cells. AP is modulated by caspases and by mitogen-activated protein kinases (MAPK) as well as by the mitochondrial membrane potential (Δψm). We studied the participation of these systems in peritoneal macrophages from ADM-treated mice. Materials and Methods: Balb/c mice were either treated with ADM (5mg/kg, i.p.) or with 0.85% NaCl solution (controls). One hour later, peritoneal cells were harvested and cultured for 28 h. AP was evaluated by ethidium bromide and acridine orange staining; Δψm was monitored using a MitoCapture stain Kit; DNA integrity was assessed by electrophoretic analysis. Animals were treated (i.p.) 1 h before ADM administration with Z-LEHD-FMK, Z-DEVD-FMK, or Z-VAD-FMK (caspase-9, caspases-3,7,10 and general caspase inhibitors, respectively) or with PD169316 (a MAPK p38 inhibitor). Results: ADM induced a higher rate of AP and the characteristic electrophoretic DNA ladder pattern. Mice treated with caspases inhibitors plus ADM showed significant reductions in AP and DNA laddering; in contrast, no differences were observed in mice treated with PD169316 plus ADM in comparison with ADM alone. ADM also induced early loss of the Δψm. Conclusion: In these experimental conditions, ADM induced AP in a mainly caspase-9-dependent manner and this was related to a reduction in the Δψm

In vivo and in vitro sensitization of leukemic cells to adriamycin-induced apoptosis by pentoxifylline: Involvement of caspase cascades and I?B? phosphorylation

The aim of this work was to investigate whether in vivo and in vitro pentoxifylline (PTX) sensitizes hematological tumor cells to adriamycin (ADM)-induced apoptosis, and to investigate the involvement of caspase cascades and phosphorylated forms of I?B?. Balb/c mice inoculated intraperitoneally with L5178-Y murine lymphoma cells were used for in vivo experiments and for survival studies. The U937 human monocytic cell line was used for in vitro experiments. Both cell lines were treated under similar experimental conditions with PTX and/or ADM to assess their effects on apoptosis. Apoptosis was evaluated by fluorescence microscopy with ethidium bromide and acridine orange staining and confirmed by electrophoretic DNA analysis. Caspase inhibitors Z-VAD-fmk, Z-DEVD-fmk, and Z-LEHD-fmk were used to investigate the involvement of caspase cascades. C-terminally and Ser32 phosphorylated forms of I?B? were evaluated in cytoplasmic extracts in the absence or presence of TNF?. Results: In vivo, PTX (50 mg/kg) with ADM (5 mg/kg) increased the apoptotic index relative to PTX or ADM administered alone, time- and dose-dependently. DNA laddering appeared in lymphoma cells treated with PTX + ADM at 24 h, whereas neither untreated control, PTX-, nor ADM-treated cells showed DNA fragmentation. All (100%) tumor-bearing mice treated with PTX (25 mg/kg) + ADM (2.5 mg/kg) survived for 1 year, whereas the mortality rates of mice treated with either PTX or ADM alone at the same doses were similar to that of untreated tumor-bearing mice (28 � 3 days). Caspase inhibitors inhibited apoptosis more efficiently in PTX- or ADM-treated cultures than in PTX + ADM-treated cultures. Pretreatment with TNF? (10 ng/mL) increased apoptosis in PTX- or ADM-treated U937 cells. However, the apoptotic index of PTX + ADM-treated cultures was significantly reduced and the expression of C-terminally and Ser32 phosphorylated I?B? was reduced. PTX sensitizes hematological malignancies to ADR-induced apoptosis. An independent caspase pathway is involved in PTX + ADM-induced apoptosis. The phosphorylation status of I?B? is closely related via TNF? to the possible mechanisms of drug resistance. � 2005 Elsevier B.V. All rights reserved

?-irradiation induced apoptosis in peritoneal macrophages by oxidative stress. Implications of antioxidants in caspase mitochondrial pathway

The in vivo and in vitro development of apoptosis induced by ?-irradiation was studied in mouse peritoneal macrophages. The apoptosis index was measured by fluorescence microscopy and DNA electrophoresis. In vivo apoptosis was greatest eight days after 8 Gy total body ?-irradiation. A DNA ladder electrophoretic pattern was only observed in the ?-irradiated group. The participation of reactive oxygen species in apoptosis induction was investigated by pretreating mice with the antioxidants superoxide dismutase, catalase, vitamin E or lipopolysaccharide before ?-irradiation. Measurement of serum lipoperoxides showed oxidative stress in the ?-irradiated mice and the protection given by the antioxidants. These results were confirmed using in vitro cultures of peritoneal macrophages: ?-irradiated groups and antioxidant-pretreated ?-irradiation groups showed results similar to those observed with in vivo irradiation. A loss of mitochondrial membrane potential (??m) was also observed by microscopy in the ?-irradiated cell cultures. Experiments with caspase inhibitors confirmed the participation of caspase 3 and caspase 9