1,721,011 research outputs found
Is FURIN gene expression in salivary glands related to SARS-CoV-2 infectivity through saliva?
No full textUnravelling the SARS-CoV-
2 mechanism of entry
into host cells is engaging the endeavours of
researchers worldwide and, although angiotensin-converting
enzyme 2 (ACE2) is recognised as
the primary receptor, many issues remain to be
investigated.1
Remarkably, the interaction between ACE2 and the
spike (S) glycosylated protein of SARS-CoV-
2 necessary
for viral entry has been discovered by employing
crystallography. S protein presents a receptor binding
domain (RBD) and more specifically a receptor
binding motif (RBM) which mediates the attachment
to two virus-binding
hotspots within ACE2 surface.
The aminoacidic constitution of SARS-CoV-
2 RBM
is highly homologous to that of SARS-CoV
but shows
some differences, specifically a four-residue
motif at
482–485 (Gly-Val-
Glu-
Gly)
that confers more affinity
for ACE2 resulting in a tight relation between the two
molecules
ATP-dependent transport of unconjugated bilirubin by rat liver canalicular plasma membrane vesicles
No full textThe transport of highly purified 3H-labelled unconjugated bilirubin (UCB) was investigated in rat liver plasma membrane vesicles enriched in the canalicular domain and found to be stimulated (more than 5-fold) by the addition of ATP. Other nucleotides, such as AMP, ADP, GTP and a non-hydrolysable ATP analogue (adenosine 5'-[alpha, beta-methylene] triphosphate), did not stimulate [3H]UCB transport, indicating that ATP hydrolysis was necessary for the stimulatory effect. [3H]UCB uptake occurred into an osmotically sensitive space. At an unbound bilirubin concentration ([Bf]) below saturation of the aqueous phase (no more than 70 nM UCB), the ATP-dependent transport followed saturation kinetics with respect to [Bf], with a Km of 26+/-8 nM and a Vmax of 117+/-11 pmol per 15 s per mg of protein. Unlabelled UCB inhibited the uptake of [3H]UCB, indicating that UCB was the transported species. Inhibitors of ATPase activity such as vanadate or diethyl pyrocarbonate decreased the ATP effect (59+/-11% and 100% respectively). Daunomycin, a known substrate for multidrug resistance protein-1, and taurocholate did not inhibit the ATP-dependent [3H]UCB transport, suggesting that neither mdr-1 nor the canalicular bile acid transporter is involved in the canalicular transport of UCB. [3H]UCB uptake (both with and without ATP) in canalicular vesicles obtained from TR- rats was comparable to that in vesicles obtained from Wistar rats, indicating that the canalicular multispecific organic anion transporter, cMOAT, does not account for UCB transport. These results indicate that UCB is transported across the canalicular membrane of the liver cell by an ATP-dependent mechanism involving an as yet unidentified transporte
SARS-CoV-2 and the next generations: which impact on reproductive tissues?
No full textCoronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) is a
severe global pandemic, affecting mostly the respiratory system. Understandably, attention is also being directed towards the
urogenital tract. In this work, expression patterns of various host molecules possibly involved in viral entry and replication were
investigated in human female and male reproductive systems by inquiring online repositories, including the Human Protein Atlas,
GTEx, FANTOM5. Our findings highlight that male reproductive tissues could be targeted by SARS-CoV-2, particularly the
testis since it co-expresses the receptor (ACE2) and the protease (TMPRSS) needed for viral entry. We hypothesized that SARSCoV-
2 infection could have repercussions on the fertility status of male individuals Potential infectivity of SARS-CoV-2 in
reproductive tissues should be considered in reproductive medicine and management of in vitro fertilization in present and future
generation
Effects of maturation on RNA transcription and protein expression of 4 MRP genes in human placenta and in BeWo cells.
No full textThe placenta is a multifunctional organ that protects the fetus from toxic compounds and the MRPs contribute to this function. The expression of MRP1, MRP2, MRP3, and MRP5 was compared in human placental tissue and in BeWo cells by real-time RT-PCR analysis; protein expression was assessed by Western blot. MRP1 and MRP3 were the most abundantly expressed genes in placenta but only MRP1 was highly expressed in the BeWo cells. Expression of MRP1 increased 4-fold in the third as compared with first trimester placental samples, and increased 20-fold with polarization of BeWo cells. MRP2, MRP3, and MRP5 were weakly expressed both in placenta and BeWo cells. Protein expression followed mRNA quantification for MRP1 and MRP5 but not for MRP2 and MRP3. These data indicated that MRP1 and MRP5 increase with trophoblast maturation, suggesting a particular role for these proteins in the organ functional development
Photobiomodulation therapy for male infertility
No full textMale infertility is a worldwide critical condition that affects about the 7.5% of males in Europe leading to an increment of the couples referring to reproductive medicine units to achieve pregnancy. Moreover, in the recent years, an increased number of patients have required to freeze their gametes in order to preserve their fertility. Photobiomodulation (PBM) therapy is a potential treatment that has been used for different clinical application basically aimed at biostimulating cells and tissues. Here, we report a deep overview of the published studies, focusing on PBM mechanism of action, with the aim of expanding the knowledge in the field of laser light for a rational utilization of irradiation in the clinical practice. In the field of reproductive science, PBM was employed to increment spermatozoa's metabolism, motility, and viability, due to its beneficial action on mitochondria, leading to an activation of the mitochondrial respiratory chain and to the ATP production. This treatment can be particularly useful to avoid the use of chemicals in the spermatozoa culture medium as well as to promote the spermatozoa survival and movement especially after thawing or in largely immotile sperm samples
Oxidative damage in DNA bases revealed by UV resonant Raman spectroscopy
Full text linkWe report on the use of the UV Raman technique to monitor the oxidative damage of deoxynucleotide triphosphates (dATP, dGTP, dCTP and dTTP) and DNA (plasmid vector) solutions. Nucleotide and DNA aqueous solutions were exposed to hydrogen peroxide (H2O2) and iron containing carbon nanotubes (CNTs) to produce Fenton's reaction and induce oxidative damage. UV Raman spectroscopy is shown to be maximally efficient to reveal changes in the nitrogenous bases during the oxidative mechanisms occurring on these molecules. The analysis of Raman spectra, supported by numerical computations, revealed that the Fenton's reaction causes an oxidation of the nitrogenous bases in dATP, dGTP and dCTP solutions leading to the production of 2-hydroxyadenine, 8-hydroxyguanine and 5-hydroxycytosine. No thymine change was revealed in the dTTP solution under the same conditions. Compared to single nucleotide solutions, plasmid DNA oxidation has resulted in more radical damage that causes the breaking of the adenine and guanine aromatic rings. Our study demonstrates the advantage of using UV Raman spectroscopy for rapidly monitoring the oxidation changes in DNA aqueous solutions that can be assigned to specific nitrogenous bases
Ferruginous bodies resolved by synchrotron XRF in a dog with peritoneal malignant mesothelioma
No full textMesothelioma is a malignant tumor mainly correlated to occupational asbestos exposure. Rare reports describe its occurrence
also in animals, mainly linked to asbestos in the environment. Asbestos exposure is demonstrated by the appearance of characteristic
histological hallmarks: asbestos containing ferruginous bodies that are iron-based structures forming around fibers and
also other dust particles. Here we present a clinical case of a suspect of mesothelioma in the peritoneum of a dog with parallel
histological observation of ferruginous bodies. To possibly correlate the dog tumor to environmental exposure, we performed Xray
fluorescence (XRF) analyses at two different synchrotrons to resolve the ferruginous bodies’ composition. While the
histological examination diagnoses a tubulo-papillary mesothelioma, the XRF analyses show that ferruginous bodies contain
Si particles, resembling formations of exogenous origin; however, the morphology is unlikely that of asbestos fibers. We
speculate that the peritoneal mesothelioma of this dog could be related to environmental exposure to non-asbestos material
Magnetic Resonance Contrast Agents: From the Bench to the Patient.
No full textMagnetic Resonance Imaging is gaining a prominent role in the routine clinical investigation. To further improve this technique it is crucial that contrast agents are developed with more optimal organ specificity. This will not only result in a better diagnostic efficiency but also in a reduction of the amount of the agent administered. A combination of techniques has been employed to increase the target selectivity of the contrast agent and thereby the feasibility to visualize different organs. The organ targeting is based on the understanding of the mechanisms involved in the interaction of the agent with plasma proteins (albumin in particular) as well as the different membrane transporters involved in the uptake and in the excretion of the agent from the organ. The physicochemical properties of the contrast agents play a major role in the interaction with these various proteins. In this review we address the relationship between the structure of the contrast agents and their binding to different plasma proteins and membrane transporters in different organs, with special reference to the liver and kidney. The present and potentially future applications of these concepts in the clinical setting are also discussed
Molecular determinants in the transport of a bile acid derived diagnostic agent in tumoral and non-tumoral cell lines of human liver.
No full textContrast-enhanced magnetic resonance imaging (CE-MRI) is a valuable technique for the diagnosis of liver diseases. As gadocoletic acid trisodium salt (B22956/1), a new contrast agent showing high biliary excretion, may be potentially advantageous in hepatobiliary imaging, the aim of the study was to investigate the molecular mechanisms of hepatic transport of the B22956 ion in a cellular model of hepatic tumor. B22956 ion uptake was measured in tumoral (HepG2) and nontumoral (Chang liver) hepatic cell lines. Absolute quantitative real-time reverse transcriptase (RT)-polymerase chain reaction (PCR) analyses, using cloned PCR products as standards, were performed on total RNA of both cell lines and normal liver to evaluate the transcription of 12 transport genes: SLCO1A2, SLCO2B1, SLCO1B1, SLCO3A1, SLCO4A1, SLCO1B3, SLC22A7, SLC22A8, SLC22A1, SLC10A1, SLC15A1, and SLC15A2. B22956 transport was more efficient in Chang liver than in HepG2 cells and was inhibited by cholecystokinin-8, a specific substrate of OATP1B3. Real-time RT-PCR analyses revealed different transcription profiles in the tumoral and nontumoral cell lines. Compared with normal liver, the expression of SLCO1B1, SLCO3A1, and SLCO1B3 was greatly repressed in HepG2 cells, whereas SLCO2B1, SLC22A7, and SLC22A8 expression was either maintained or increased. On the contrary, in Chang liver cells, SLC22A7 and SLC22A8 genes were undetectable, whereas the expression of SLCO3A1, SLCO4A1, and SLCO1B3 was similar to normal liver. Transport studies and gene expression analyses indicated that B22956 ion is a good substrate to the liver-specific OATP1B3, reported to be poorly expressed or absent in human liver tumors. Therefore, B22956 may be helpful in detecting hepatic neoplastic lesions by CE-MRI
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