Background Neonatal sepsis remains an important cause of morbidity and mortality. The ability to quickly and accurately diagnose neonatal sepsis based on clinical assessments and laboratory blood tests remains difficult, where haemoculture is the gold standard for detecting bacterial sepsis in blood culture. It is also very difficult to study because neonatal samples are lacking. Methods Forty-eight newborns suspected of sepsis admitted to the Neonatology Department of the Mother-Child Specialized Hospital of Tlemcen. From each newborn, a minimum of 1–2 ml of blood was drawn by standard sterile procedures for blood culture. The miRNA-23b level in haemoculture was evaluated by RT-qPCR. Results miR-23b levels increased in premature and full-term newborns in early onset sepsis (p < 0.001 and p < 0.005 respectively), but lowered in late onset sepsis in full-term neonates (p < 0.05) compared to the respective negative controls. miR-23b levels also increased in late sepsis in the negative versus early sepsis negative controls (p < 0.05). miR-23b levels significantly lowered in the newborns who died from both sepsis types (p < 0.0001 and p < 0.05 respectively). In early sepsis, miR-23b and death strongly and negatively correlated (correlation coefficient = − 0.96, p = 0.0019). In late sepsis, miRNA-23b and number of survivors (correlation coefficient = 0.70, p = 0.506) positively correlated. Conclusions Lowering miR-23b levels is an important factor that favours sepsis development, which would confirm their vital protective role, and strongly suggest that they act as a good marker in molecular diagnosis and patient monitoring.
Sepsis carries a substantial risk of morbidity and mortality in newborns, especially preterm-born neonates. Endothelial glycocalyx (eGC) is a carbohydrate-rich layer lining the vascular endothelium, with important vascular barrier function and cell adhesion properties, serving also as a mechano-sensor for blood flow. eGC shedding is recognized as a fundamental pathophysiological process generating microvascular dysfunction, which in turn contributes to multiple organ failure and death in sepsis. Although the disruption of eGC and its consequences have been investigated intensively in the adult population, its composition, development, and potential mechanisms of action are still poorly studied during the neonatal period, and more specifically, in neonatal sepsis. Further knowledge on this topic may provide a better understanding of the molecular mechanisms that guide the sepsis pathology during the neonatal period, and would increase the usefulness of endothelial glycocalyx dysfunction as a diagnostic and prognostic biomarker. We reviewed several components of the eGC that help to deeply understand the mechanisms involved in the eGC disruption during the neonatal period. In addition, we evaluated the potential of eGC components as biomarkers and future targets to develop therapeutic strategies for neonatal sepsis.
In recent years, cancer treatment has undergone significant changes, predominantly in the shift towards immunotherapeutic strategies using immune checkpoint inhibitors. Despite the clinical efficacy of many of these inhibitors, the overall response rate remains modest, and immunotherapies for many cancers have proved ineffective, highlighting the importance of knowing the tumor microenvironment and heterogeneity of each malignancy in patients. Long non-coding RNAs (lncRNAs) have attracted increasing attention for their ability to control various biological processes by targeting different molecular pathways. Some lncRNAs have a regulatory role in immune checkpoints, suggesting they might be utilized as a target for immune checkpoint treatment. The focus of this review is to describe relevant lncRNAs and their targets and functions to understand key regulatory mechanisms that may contribute in regulating immune checkpoints. We also provide the state of the art on super-enhancers lncRNAs (selncRNAs) and circular RNAs (circRNAs), which have recently been reported as modulators of immune checkpoint molecules within the framework of human cancer. Other feasible mechanisms of interaction between lncRNAs and immune checkpoints are also reported, along with the use of miRNAs and circRNAs, in generating new tumor immune microenvironments, which can further help avoid tumor evasion.
Background: Neonatal sepsis remains an important cause of morbidity and mortality. The ability to quickly and accurately diagnose neonatal sepsis based on clinical assessments and laboratory blood tests remains difficult, where haemoculture is the gold standard for detecting bacterial sepsis in blood culture. It is also very difficult to study because neonatal samples are lacking. Methods : Forty-eight newborns suspected of sepsis admitted to the Neonatology Department of the Mother-Child Specialized Hospital of Tlemcen. From each newborn, a minimum of 1-2 ml of blood was drawn by standard sterile procedures for blood culture. The miRNA-23b level in haemoculture was evaluated by RT-qPCR. Results : miR-23b levels increased in premature and full-term newborns in early onset sepsis ( p < 0.001 and p < 0.005 respectively), but lowered in late onset sepsis in full-term neonates ( p < 0.05) compared to the respective negative controls. miR-23b levels also increased in late sepsis in the negative versus early sepsis negative controls ( p < 0.05). miR-23b levels significantly lowered in the newborns who died from both sepsis types ( p < 0.0001 and p < 0.05 respectively). In early sepsis, miR-23b and death strongly and negatively correlated (correlation coefficient = -0.96, p = 0.0019). In late sepsis, miRNA-23b and number of survivors (correlation coefficient = 0.70, p = 0.506) positively correlated. Conclusions : Lowering miR-23b levels is an important factor that favours sepsis development, which would confirm their vital protective role, and strongly suggest that they act as a good marker in molecular diagnosis and patient monitoring.
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