RESUMO
Schistosomiasis is a neglected tropical disease caused by worm parasites of the genus Schistosoma. Upon infection, parasite eggs can lodge inside of host organs like the liver. This leads to granuloma formation, which is the main cause of the pathology of schistosomiasis. To better understand the different levels of host-pathogen interaction and pathology, our study focused on the characterization of glycosphingolipids (GSLs). For this purpose, GSLs in livers of infected and noninfected hamsters were studied by combining high-spatial-resolution atmospheric-pressure scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry imaging (AP-SMALDI MSI) with nanoscale hydrophilic interaction liquid chromatography tandem mass spectrometry (nano-HILIC MS/MS). Nano-HILIC MS/MS revealed 60 GSL species with a distinct saccharide and ceramide composition. AP-SMALDI MSI measurements were conducted in positive- and negative-ion mode for the visualization of neutral and acidic GSLs. Based on nano-HILIC MS/MS results, we discovered no downregulated but 50 significantly upregulated GSLs in liver samples of infected hamsters. AP-SMALDI MSI showed that 44 of these GSL species were associated with the granulomas in the liver tissue. Our findings suggest an important role of GSLs during granuloma formation.
Assuntos
Glicoesfingolipídeos , Fígado , Schistosoma mansoni , Esquistossomose mansoni , Animais , Glicoesfingolipídeos/metabolismo , Glicoesfingolipídeos/química , Fígado/metabolismo , Fígado/parasitologia , Cricetinae , Esquistossomose mansoni/parasitologia , Esquistossomose mansoni/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas em Tandem , Mesocricetus , Cromatografia Líquida , MasculinoRESUMO
Schistosomiasis, a widespread neglected tropical disease, presents a complex and multifaceted clinical-pathological profile. Using hamsters as final hosts, we dissected molecular events following Schistosoma mansoni infection in the liver-the organ most severely affected in schistosomiasis patients. Employing tandem mass tag-based proteomics, we studied alterations in the liver proteins in response to various infection modes and genders. We examined livers from female and male hamsters that were: noninfected (control), infected with either unisexual S. mansoni cercariae (single-sex) or both sexes (bisex). The infection induced up-regulation of proteins associated with immune response, cytoskeletal reorganization, and apoptotic signaling. Notably, S. mansoni egg deposition led to the down-regulation of liver factors linked to energy supply and metabolic processes. Gender-specific responses were observed, with male hamsters showing higher susceptibility, supported by more differentially expressed proteins than found in females. Of note, metallothionein-2 and S100a6 proteins exhibited substantial up-regulation in livers of both genders, suggesting their pivotal roles in the liver's injury response. Immunohistochemistry and real-time-qPCR confirmed strong up-regulation of metallothionein-2 expression in the cytoplasm and nucleus upon the infection. Similar findings were seen for S100a6, which localized around granulomas and portal tracts. We also observed perturbations in metabolic pathways, including down-regulation of enzymes involved in xenobiotic biotransformation, cellular energy metabolism, and lipid modulation. Furthermore, lipidomic analyses through liquid chromatography-tandem mass spectrometry and matrix-assisted laser desorption/ionization mass spectrometry imaging identified extensive alterations, notably in cardiolipin and triacylglycerols, suggesting specific roles of lipids during pathogenesis. These findings provide unprecedented insights into the hepatic response to S. mansoni infection, shedding light on the complexity of liver pathology in this disease.
RESUMO
Odor-active fatty aldehydes are important compounds for the flavor and fragrance industry. By a coupled enzymatic reaction using an α-dioxygenase (α-DOX) and an aldehyde dehydrogenase (FALDH), scarcely available aldehydes from the biotransformation of margaroleic acid [17:1(9Z)] were characterized and have shown highly interesting odor profiles, including citrus-like, soapy, herbaceous, and savory notes. In particular, (Z)-8-hexadecenal and (Z)-7-pentadecenal exhibited notable meaty odor characteristics. Submerged cultivation of Mortierella hyalina revealed the accumulation of the above-mentioned, naturally uncommon fatty acid 17:1(9Z). Its production was significantly increased by the modulation of culture conditions, whereas the highest accumulation was observed after 4 days at 24 °C and l-isoleucine supplementation. The lipase-, α-DOX-, and FALDH-mediated biotransformation of M. hyalina lipid extract resulted in a complex aldehyde mixture with a high aldehyde yield of â¼50%. The odor qualities of the formed aldehydes were assessed by means of gas chromatography-olfactometry, and several of the obtained fatty aldehydes have been sensorially described for the first time. To assess the aldehyde mixture's potential as a flavor ingredient, a sensory evaluation was conducted. The obtained product exhibited intense citrus-like, green, and soapy odor impressions.