Laparoscopic cholecystectomy is the Gold Standard for the treatment of symptomatic cholelithiasis. There is still an increase in the rate of incidence of biliary and vascular injuries with ...laparoscopy. Hepatic artery pseudoaneurysm is a rare but serious complication associated with laparoscopic cholecystectomy and bile duct injury. The diagnosis may be difficult. Our experience of a case of iatrogenic lesion of the right hepatic artery with the formation of pseudoaneurysm treated by means of embolization of the artery is presented here.
ABSTRACT
Nonsteroidal antiinflammatory drugs and analgesic drugs, such as N‐acetyl‐p‐aminophenol (APAP; acetaminophen, paracetamol), are widely used by pregnant women. Accumulating evidence has ...indicated that these molecules can favor genital malformations in newborn boys and reproductive disorders in adults. However, the consequences on postnatal testis development and adult reproductive health after exposure during early embryo‐genesis are still unknown. Using the mouse model, we show that in utero exposure to therapeutic doses of the widely used APAP‐ibuprofen combination during the sex determination period leads to early differentiation and decreased proliferation of male embryonic germ cells, and early 5‐mefhylcytosine and extracellular matrix protein deposition in 13.5 d postcoitum exposed testes. Consequently, in postnatal testes, Sertoli‐cell maturation is delayed, the Leydig‐cell compartment is hyperplasia and the spermatogonia A pool is decreased. This results in a reduced production of testosterone and in epididymal sperm parameter defects. We observed a reduced sperm count (19%) in utero–exposed (FO) adult males and also a reduced sperm motility (40%) in their offspring (Fl) when both parents were exposed, which leads to subfertility among the 6 mo old Fl animals. Our study suggests that the use of these drugs during the critical period of sex determination affects the germ‐line development and leads to adverse effects that could be passed to the offspring.—Rossitto, M., Marchive, C., Pruvost, A., Sellem, E., Ghettas, A., Badiou, S., Sutra, T., Poulat, F., Philibert, P., Boizet‐Bonhoure, B. Intergenerational effects on mouse sperm quality after in utero exposure to acetaminophen and ibuprofen. FASEB J. 33, 339–357 (2019). www.fasebj.org
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) is encoded by a major autoimmunity gene and is a known inhibitor of T cell receptor (TCR) signaling and drug target for cancer immunotherapy. ...However, little is known about PTPN22 posttranslational regulation. Here, we characterize a phosphorylation site at Ser325 situated C terminal to the catalytic domain of PTPN22 and its roles in altering protein function. In human T cells, Ser325 is phosphorylated by glycogen synthase kinase-3 (GSK3) following TCR stimulation, which promotes its TCR-inhibitory activity. Signaling through the major TCR-dependent pathway under PTPN22 control was enhanced by CRISPR/Cas9-mediated suppression of Ser325 phosphorylation and inhibited by mimicking it via glutamic acid substitution. Global phospho-mass spectrometry showed Ser325 phosphorylation state alters downstream transcriptional activity through enrichment of Swi3p, Rsc8p, and Moira domain binding proteins, and next-generation sequencing revealed it differentially regulates the expression of chemokines and T cell activation pathways. Moreover, in vitro kinetic data suggest the modulation of activity depends on a cellular context. Finally, we begin to address the structural and mechanistic basis for the influence of Ser325 phosphorylation on the protein’s properties by deuterium exchange mass spectrometry and NMR spectroscopy. In conclusion, this study explores the function of a novel phosphorylation site of PTPN22 that is involved in complex regulation of TCR signaling and provides details that might inform the future development of allosteric modulators of PTPN22.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Omega-3 fatty acids (n-3 PUFAs) are essential for the functional maturation of the brain. Westernization of dietary habits in both developed and developing countries is accompanied by a progressive ...reduction in dietary intake of n-3 PUFAs. Low maternal intake of n-3 PUFAs has been linked to neurodevelopmental diseases in Humans. However, the n-3 PUFAs deficiency-mediated mechanisms affecting the development of the central nervous system are poorly understood. Active microglial engulfment of synapses regulates brain development. Impaired synaptic pruning is associated with several neurodevelopmental disorders. Here, we identify a molecular mechanism for detrimental effects of low maternal n-3 PUFA intake on hippocampal development in mice. Our results show that maternal dietary n-3 PUFA deficiency increases microglia-mediated phagocytosis of synaptic elements in the rodent developing hippocampus, partly through the activation of 12/15-lipoxygenase (LOX)/12-HETE signaling, altering neuronal morphology and affecting cognitive performance of the offspring. These findings provide a mechanistic insight into neurodevelopmental defects caused by maternal n-3 PUFAs dietary deficiency.
Germ cells, the precursors of gametes, represent a unique cell lineage that is able to differentiate into spermatozoa or oocytes depending on the chromosomal sex of the organism. In the mammalian ...embryonic gonad, commitment to oogenesis involves pre-meiotic DNA replication and entry into the first meiotic division; whereas, commitment to spermatogenesis involves inhibition of meiotic initiation, suppression of pluripotency, mitotic arrest and expression of specific markers that will control the development of the male germ cells. The crucial decision made by the germ line to commit to either a male or a female fate has been partially explained by genetic and ex vivo studies in mice which have implicated a complex network of regulatory genes, numerous factors and pathways. Besides the reproductive failure that may follow a deregulation of this complex network, the germ cells may, in view of their proliferative and pluripotent nature, act as precursors of potential malignant transformation and as putative targets for exogenous environmental compounds. Our review summarizes and discusses recent developments that have improved our understanding on how germ cell precursors are committed to a male or a female cell fate in the mouse gonad.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Prostaglandins signaling molecules are involved in numerous physiological processes. They are produced by several enzyme-limited reactions upon fatty acids, which are catalyzed by two cyclooxygenases ...and prostaglandin synthases. In particular, the prostaglandins E2 (PGE2), D2 (PGD2), and F2 (PGF2 α) have been shown to be involved in female reproductive mechanisms. Furthermore, widespread expression of lipocalin- and hematopoietic-PGD2 synthases in the male reproductive tract supports the purported roles of PGD2 in the development of both embryonic and adult testes, sperm maturation, and spermatogenesis. In this review, we summarize the putative roles of PGD2 signaling and the roles of both PGD2 synthases in testicular formation and function. We review the data reporting the involvement of PGD2 signaling in the differentiation of Sertoli and germ cells of the embryonic testis. Furthermore, we discuss the roles of lipocalin-PGD2 synthase in steroidogenesis and spermatogenesis, in terms of lipid molecule transport and PGD2 production. Finally, we discuss the hypothesis that PGD2 signaling may be affected in certain reproductive diseases, such as infertility, cryptorchidism, and testicular cancer.
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