miR-210 is overexpressed in late stages of lung cancer and mediates mitochondrial alterations associated with modulation of HIF-1 activity.

Following the identification of a set of hypoxia-regulated microRNAs (miRNAs), recent studies have highlighted the importance of miR-210 and of its transcriptional regulation by the transcription factor hypoxia-inducible factor-1 (HIF-1). We report here that miR-210 is overexpressed at late stages of non-small cell lung cancer. Expression of miR-210 in lung adenocarcinoma A549 cells caused an alteration of cell viability associated with induction of caspase-3/7 activity. miR-210 induced a loss of mitochondrial membrane potential and the apparition of an aberrant mitochondrial phenotype. The expression profiling of cells overexpressing miR-210 revealed a specific signature characterized by enrichment for transcripts related to 'cell death' and 'mitochondrial dysfunction', including several subunits of the electron transport chain (ETC) complexes I and II. The transcript coding for one of these ETC components, SDHD, subunit D of succinate dehydrogenase complex (SDH), was validated as a bona fide miR-210 target. Moreover, SDHD knockdown mimicked miR-210-mediated mitochondrial alterations. Finally, miR-210-dependent targeting of SDHD was able to activate HIF-1, in line with previous studies linking loss-of-function SDH mutations to HIF-1 activation. miR-210 can thus regulate mitochondrial function by targeting key ETC component genes with important consequences on cell metabolism, survival and modulation of HIF-1 activity. These observations help explain contradictory data regarding miR-210 expression and its putative function in solid tumors.

Tumor necrosis factor-alpha stimulates HIV-1 production in primary culture of human adipocytes.

Adipose tissue of HIV-1-infected patients shows severe abnormalities such as profound changes in adipose tissue morphology and metabolism. Does HIV-1 infect the adipose cell remains an unsolved question since previous attempts showed that HIV-1 poorly infects human adipocytes in vitro. In the present study, preadipose cells from human subcutaneous fat pads were differentiated in vitro, checked for HIV receptor expression, then infected with R5 and X4 HIV1 strains. Using a sensitive RT-PCR assay, we showed that HIV-1 tat and rev early viral transcripts were expressed in infected adipocytes giving a clear evidence of HIV-1 transcriptional activity in these cells. However, at the same time, no sign of productive infection was demonstrated since infected adipocytes did not efficiently produce Gag p24 antigen. We hypothesized that such a limitation could result from the lack of activation of adipocyte-signaling pathways able to stimulate HIV-1 gene expression in quiescent adipocytes. Indeed, a significant increase in Gag p24 production was observed after stimulation of infected adipocytes with pro-inflammatory cytokines, such as tumor necrosis factor alpha or interleukin-1-beta. Taken together, these results demonstrate that HIV-1 does infect human adipose cells in vitro and suggest that the initial limited infection can be overcome upon pro-inflammatory cytokine treatment.

Neuroanatomical and neuropharmacological study of opioid pathways in the mesencephalic tectum: effect of mu(1)- and kappa-opioid receptor blockade on escape behavior induced by electrical stimulation of the inferior colliculus.

Deep layers of the superior colliculus (DLSC), the dorsal and ventral periaqueductal gray matter (PAG), and inferior colliculus (IC) are midbrain structures involved in the generation of defensive behavior. beta-Endorphin and Leu-enkephalin are some neurotransmitters that may modulate such behavior in mammals. Light microscopy immunocytochemistry with streptavidin method was used for the localization of the putative cells of defensive behavior with antibodies for endogenous opioids in rat brainstem. Midbrain structures showed positive neurons to beta-endorphin and Leu-enkephalin in similar distributions in the experimental animals, but we also noted the presence of varicose fibers positive to endogenous opioids in the PAG. Neuroanatomical techniques showed varicose fibers from the central nucleus of the inferior colliculus to ventral aspects of the PAG, at more caudal levels. Naloxonazine and nor-binaltorphimine, competitive antagonists that block mu(1)- and kappa-opioid receptors, were then used in the present work to investigate the involvement of opioid peptide neural system in the control of the fear-induced reactions evoked by electrical stimulation of the neural substrates of the inferior colliculus. The fear-like responses were measured by electrical stimulation of the central nucleus of the inferior colliculus, eliciting the escape behavior, which is characterized by vigorous running and jumping. Central administration of opioid antagonists (2.5 microg/0.2 microl and 5.0 microg/0.2 microl) was performed in non-anesthetized animals (Rattus norvegicus), and the behavioral manifestations of fear were registered after 10 min, 2 h, and 24 h of the pretreatment. Naloxonazine caused an increase of the defensive threshold, as compared to control, suggesting an antiaversive effect of the antagonism on mu(1)-opioid receptor. This finding was corroborated with central administration of nor-binaltorphimine, which also induced a decrease of the fear-like responses evoked by electrical stimulation of the inferior colliculus, since the threshold of the escape behavior was increased 2 and 24 h after the blockade of kappa-opioid receptor. These results indicate that endogenous opioids may be involved in the modulation of fear in the central nucleus of the inferior colliculus. Although the acute treatment (after 10 min) of both naloxonazine and nor-binaltorphimine causes nonspecific effect on opioid receptors, we must consider the involvement of mu(1)- and kappa-opioid receptors in the antiaversive influence of the opioidergic interneurons in the dorsal mesencephalon, at caudal level, after chronic (2-24 h) treatment of these opioid antagonists. The neuroanatomical study of the connections between the central nucleus of the inferior colliculus and the periaqueductal gray matter showed neuronal fibers with varicosities and with terminal bottons, both in the pericentral nucleus of the inferior colliculus and in ventral and dorsal parts of caudal aspects of the periaqueductal gray matter.

A peptide derived from bee venom-secreted phospholipase A2 inhibits replication of T-cell tropic HIV-1 strains via interaction with the CXCR4 chemokine receptor.

We have previously shown that secreted phospholipases A2 (sPLA2) from bee and snake venoms have potent anti-human immunodeficiency virus (HIV) activity. These sPLA2s block HIV-1 entry into host cells through a mechanism linked to sPLA2 binding to cells. In this study, 12 synthetic peptides derived from bee venom sPLA2 (bvPLA2) have been tested for inhibition of HIV-1 infection. The p3bv peptide (amino acids 21 to 35 of bvPLA2) was found to inhibit the replication of T-lymphotropic (T-tropic) HIV-1 isolates (ID(50) = 2 microM) but was without effect on monocytotropic (M-tropic) HIV-1 isolates. p3bv was also found capable of preventing the cell-cell fusion process mediated by T-tropic HIV-1 envelope. Finally, p3bv can inhibit the binding of radiolabeled stromal cell-derived factor (SDF)-1alpha, the natural ligand of CXCR4, and the binding of 12G5, an anti-CXCR4 monoclonal antibody. Taken together, these results indicate that p3bv blocks the replication of T-tropic HIV-1 strains by interacting with CXCR4. Its mechanism of action however appears distinct from that of bvPLA2 because the latter inhibits replication of both T-tropic and M-tropic isolates and does not compete with SDF-1alpha and 12G5 binding to CXCR4.

[Retention jaundice caused by central hepatic hepatoma. Treatment with Kron's extra-anatomic biliary prosthesis]. / Ictère rétentionnel par hépatome centro-hépatique. Traitement par prothèse biliaire de Kron à trajet extra-anatomique.

A 31 year-old patient presented with a retention jaundice from a centrally located hepatoma invading the hilum. Because of the patient's age and the severity of the pruritus and jaundice, palliative treatment was performed by percutaneous catheterization of the intrahepatic biliary tracts to drain the right and left hepatic canals. As the hilar stenosis could not be overcome, the external drainage was transformed into internal drainage by implantation of a Kron's biliary prosthesis linking the intrahepatic biliary tracts, following segment III hepatotomy, to the duodenal lumen, with burying of the prosthesis in the gastric antrum region. Jaundice was reduced until death of the patients from metastases 6 months later. This case demonstrates that the use of Kron's biliary prosthesis to perform a biliodigestive shunt from intrahepatic biliary pathways is a valid palliative procedure in patients with limited life expectancies.

[Uterine and sigmoid perforations following voluntary interruption of pregnancy by aspiration. A case report (author's transl)]. / Perforation utérine et sigmoïdienne après interruption volontaire de grossesse par aspiration. A propos d'un cas.

A recent case of mixed uterine and colic perforations associated with generalized peritonitis is reported, the lesions developing within the context of the digestive complications of the method known as aspiration for voluntary interruption of pregnancy. The frequency, severity, and treatment of these lesions are described, urgent laparotomy being necessary to correct both abdominal digestive tract and genital lesions. Prevention of these complication technique. Coelioscopy is essential if a perforation is suspected, and must be followed by a laparotomy if its presence is confirmed.