Multidrug resistance conferring proteins (MDRCP) are ATP-binding cassette (ABC) transporters known to significantly influence the absorption, distribution, metabolism, and elimination (ADME) and ...toxic behavior of many therapeutic agents. Research in the pharmacogenomics area has suggested that mutations and variable expression patterns of these MDCRPs may exist in tissue samples from different ethnic groups. The goal of this study was to examine the expression of P-glycoprotein (PGP), sister of PGP (S-PGP), multidrug resistance protein 3 (Mdr3), multidrug resistance like proteins 1−5 (MRP 1−5), and lung resistance associated protein (LRP) in tissue slides and protein lysates derived from normal adult small or large intestines of Caucasian or Chinese origin. Our results demonstrated ubiquitous expression of PGP, MRP 1, MRP 4, and LRP in the small and large intestinal epitheliums originating from both Caucasian and Chinese origin. S-PGP, Mdr3, MRP 2, and MRP 3 exhibited variable expression in the tissue slides and protein lysates derived from the Chinese and Caucasian small and large intestines. MRP 5 was not observed in any of the samples studied. The results suggest that MDCRPs may have distinct expression profiles in the small and large intestines that potentially vary with genetic background. These studies provide a foundation for further investigations to verify these findings across a wider number of patients of different ethnic backgrounds. Keywords: Multidrug resistance; LRP; MRP; Mdr; P-glycoprotein
The ontogeny of human haematopoietic stem cells (HSCs) is poorly defined owing to the inability to identify HSCs as they emerge and mature at different haematopoietic sites
. Here we created a ...single-cell transcriptome map of human haematopoietic tissues from the first trimester to birth and found that the HSC signature RUNX1
HOXA9
MLLT3
MECOM
HLF
SPINK2
distinguishes HSCs from progenitors throughout gestation. In addition to the aorta-gonad-mesonephros region, nascent HSCs populated the placenta and yolk sac before colonizing the liver at 6 weeks. A comparison of HSCs at different maturation stages revealed the establishment of HSC transcription factor machinery after the emergence of HSCs, whereas their surface phenotype evolved throughout development. The HSC transition to the liver marked a molecular shift evidenced by suppression of surface antigens reflecting nascent HSC identity, and acquisition of the HSC maturity markers CD133 (encoded by PROM1) and HLA-DR. HSC origin was tracked to ALDH1A1
KCNK17
haemogenic endothelial cells, which arose from an IL33
ALDH1A1
arterial endothelial subset termed pre-haemogenic endothelial cells. Using spatial transcriptomics and immunofluorescence, we visualized this process in ventrally located intra-aortic haematopoietic clusters. The in vivo map of human HSC ontogeny validated the generation of aorta-gonad-mesonephros-like definitive haematopoietic stem and progenitor cells from human pluripotent stem cells, and serves as a guide to improve their maturation to functional HSCs.
In the last decade, extended-spectrum cephalosporin and carbapenem resistant Gram-negative bacilli (GNB) have been extensively reported in the literature as being disseminated in humans but also in ...animals and the environment. These resistant organisms often cause treatment challenges due to their wide spectrum of antibiotic resistance. With the emergence of colistin resistance in animals and its subsequent detection in humans, the situation has worsened. Several studies reported the transmission of resistant organisms from animals to humans. Studies from the middle east highlight the spread of resistant organisms in hospitals and to a lesser extent in livestock and the environment. In view of the recent socio-economical conflicts that these countries are facing in addition to the constant population mobilization; we attempt in this review to highlight the gaps of the prevalence of resistance, antibiotic consumption reports, infection control measures and other risk factors contributing in particular to the spread of resistance in these countries. In hospitals, carbapenemases producers appear to be dominant. In contrast, extended spectrum beta lactamases (ESBL) and colistin resistance are becoming a serious problem in animals. This is mainly due to the continuous use of colistin in veterinary medicine even though it is now abandoned in the human sphere. In the environment, despite the small number of reports, ESBL and carbapenemases producers were both detected. This highlights the importance of the latter as a bridge between humans and animals in the transmission chain. In this review, we note that in the majority of the Middle Eastern area, little is known about the level of antibiotic consumption especially in the community and animal farms. Furthermore, some countries are currently facing issues with immigrants, poverty and poor living conditions which has been imposed by the civil war crisis. This all greatly facilitates the dissemination of resistance in all environments. In the one health concept, this work re-emphasizes the need to have global intervention measures to avoid dissemination of antibiotic resistance in humans, animals and the environment in Middle Eastern countries.
As SARS-CoV-2 continues to be relevant and cause illnesses, the effect of emerging virus variants on perinatal health remains to be elucidated. It was demonstrated that vertical transmission of ...SARS-CoV-2 is a relatively rare event in the original SARS-CoV-2 strain. However, very few reports describe vertical transmission related to the delta-variant.
We report a case of a preterm male neonate born to a mother with positive SARS-CoV-2 and mild respiratory complications. The neonate was born by cesarean section due to fetal distress. The rupture of the amniotic membrane was at delivery. The neonate had expected prematurity-related complications. His nasopharyngeal swabs for RT-PCR were positive from birth till three weeks of age. RT-ddPCR of the Placenta showed a high load of the SARS-CoV-2 virus with subgenomic viral RNA. RNAscope technique demonstrated both the positive strand of the S gene and the orf1ab negative strand. Detection of subgenomic RNA and the orf1ab negative strand indicats active viral replication in the placenta.
Our report demonstrates active viral replication of the SARS-CoV-2 delta-variant in the placenta associated with vertical transmission in a preterm infant.
Pregnancy represents a unique challenge for the maternal-fetal immune interface, requiring a balance between immunosuppression, which is essential for the maintenance of a semiallogeneic fetus, and ...proinflammatory host defense to protect the maternal-fetal interface from invading organisms. Adaptation to repeated inflammatory stimuli (endotoxin tolerance) may be critical in preventing inflammation-induced preterm birth caused by exaggerated maternal inflammatory responses to mild or moderate infections that are common during pregnancy. However, the exact mechanisms contributing to the maintenance of tolerance to repeated infections are not completely understood. MicroRNAs play important roles in pregnancy with several microRNAs implicated in gestational tissue function and in pathologic pregnancy conditions. MicroRNA-519c, a member of the chromosome 19 microRNA cluster, is a human-specific microRNA mainly expressed in the placenta. However, its role in pregnancy is largely unknown.
This study aimed to explore the role of “endotoxin tolerance” failure in the pathogenesis of an exaggerated inflammatory response often seen in inflammation-mediated preterm birth. In this study, we investigated the role of microRNA-519c, a placenta-specific microRNA, as a key regulator of endotoxin tolerance at the maternal-fetal interface.
Using a placental explant culture system, samples from term and second-trimester placentas were treated with lipopolysaccharide. After 24 hours, the conditioned media were collected for analysis, and the placental explants were re-exposed to repeated doses of lipopolysaccharide for 3 days. The supernatant was analyzed for inflammatory markers, the presence of extracellular vesicles, and microRNAs. To study the possible mechanism of action of the microRNAs, we evaluated the phosphodiesterase 3B pathway involved in tumor necrosis factor alpha production using a microRNA mimic and phosphodiesterase 3B small interfering RNA transfection. Finally, we analyzed human placental samples from different gestational ages and from women affected by inflammation-associated pregnancies.
Our data showed that repeated exposure of the human placenta to endotoxin challenges induced a tolerant phenotype characterized by decreased tumor necrosis factor alpha and up-regulated interleukin-10 levels. This reaction was mediated by the placenta-specific microRNA-519c packaged within placental extracellular vesicles. Lipopolysaccharide treatment increased the extracellular vesicles that were positive for the exosome tetraspanin markers, namely CD9, CD63, and CD81, and secreted primarily by trophoblasts. Primary human trophoblast cells transfected with a microRNA-519c mimic decreased phosphodiesterase 3B, whereas a lack of phosphodiesterase 3B, achieved by small interfering RNA transfection, led to decreased tumor necrosis factor alpha production. These data support the hypothesis that the anti-inflammatory action of microRNA-519c was mediated by a down-regulation of the phosphodiesterase 3B pathway, leading to inhibition of tumor necrosis factor alpha production. Furthermore, human placentas from normal and inflammation-associated pregnancies demonstrated that a decreased placental microRNA-519c level was linked to infection-induced inflammatory pathologies during pregnancy.
We identified microRNA-519c, a human placenta-specific microRNA, as a novel regulator of immune adaptation associated with infection-induced preterm birth at the maternal-fetal interface. Our study serves as a basis for future experiments to explore the potential use of microRNA-519c as a biomarker for infection-induced preterm birth.
Abstract Eosinophilic appendicitis is a rare inflammatory condition characterized by the infiltration of eosinophils into the appendix, which is often misdiagnosed as acute appendicitis given ...similarities in their clinical presentation. Acute eosinophilic appendicitis: a rare cause of lower gastrointestinal hemorrhage. Within this particular report, we present a case of eosinophilic appendicitis in a 42-year-old female who underwent a laparoscopic appendectomy. The purpose of this report is to increase awareness about this unique condition and emphasize the importance of considering eosinophilic appendicitis as a differential diagnosis in patients with appendicitis-like symptoms whose clinical examination and laboratory findings may suggest otherwise.
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