Effect of dexmedetomidine on perioperative haemodynamics and early cognitive function in elderly patients undergoing laparoscopic surgery.

Introduction: Laparoscopic minimally invasive surgery has been widely used in the diagnosis and treatment of gynaecological diseases. Aim: To investigate the effect of dexmedetomidine on perioperative haemodynamics and cognitive function in elderly gynaecological patients who underwent laparoscopic surgery. Material and methods: Clinical baseline characteristics, haemodynamic parameters, renin activity, norepinephrine level, cognitive function, pain level, and sedation were compared between the 2 groups. Results: At T4 (10 min after extubation) and T5 (1 h after extubation), significant differences were found in systolic blood pressure, diastolic blood pressure, and heart rate between the 2 groups (p < 0.05); renin activity and norepinephrine level were much lower in the dexmedetomidine group than in the control group at T3 (10 min before extubation) and T4 (p < 0.05). One day before surgery, there were no significant differences in Mini-mental state examination (MMSE), visual analogue scale (VAS), and Ramsay scores between the 2 groups (p > 0.05), but the MMSE score 1 day after surgery and the Ramsay score at 12 h after surgery in the dexmedetomidine group were much higher than that in the control group (p < 0.05). Notably, at 2, 4, 12, 24, and 48 h after surgery, the VAS score in the dexmedetomidine group was significantly lower than that in the control group (p < 0.05). Conclusions: Dexmedetomidine has a better clinical effect in improving perioperative haemodynamics and early cognitive function in elderly gynaecological patients who received laparoscopic surgery.

Immune functions of the Dscam extracellular variable region in Chinese mitten crab.

In arthropods, there is only a single copy of Down Syndrome Cell Adhesion Molecule (Dscam) in the genome, but it can exist as numerous splice variants. There are three hypervariable exons in the extracellular domain and one hypervariable exon in the transmembrane domain. In Chinese mitten crab (Eriocheir sinensis), exons 4, 6 and 14 can produce 25, 34 and 18 alternative splice variants, respectively. In this study, through Illumina sequencing, we identified additional splice variants for exons 6 and 14, hence there may be > 50,000 Dscam protein variants. Sequencing of exons 4, 6 and 14 showed that alternative splicing was altered after bacterial stimulation. Therefore, we expressed and purified the extracellular variable region of Dscam (EsDscam-Ig1-Ig7). Exons 4.3, 6.46 and 14.18, three variable exons of the recombinant protein, were randomly selected. The functions of EsDscam-Ig1-Ig7 in immune defences of E. sinensis were subsequently explored. EsDscam-Ig1-Ig7 was discovered to bind to both Gram-positive Staphylococcus aureus and Gram-negative Vibrio parahaemolyticus, but it did not exhibit antibacterial activity. By promoting hemocyte phagocytosis and bacterial removal, EsDscam-Ig1-Ig7 can also shield the host from bacterial infection. The findings highlight the immunological activities of Dscam alternative splicing and reveal the potential for many more Dscam isoforms than were previously predicted in E. sinensis.

Suppressed COP9 signalosome 5 promotes hemocyte proliferation through Cyclin E in the early G1 phase to defend against bacterial infection in crab.

Hemocytes are invertebrate immune cells that are similar to blood cells in vertebrates and play a crucial role in innate immunity. Previous work has found that mature circulating hemocytes lack the ability to proliferate. However, recent single-cell RNA sequencing and functional studies in invertebrate have challenged this view. Here, we report that bacteria induced hemocytes proliferation in the Chinese mitten crab, Eriocheir sinensis. Flow cytometry was used to collect non-proliferating and proliferating hemocytes populations, while the expression of EsCyclin E was highly expressed in proliferating hemocytes, but the expression of EsCsn5 was significantly suppressed in proliferating hemocytes. Subsequent studies have found EsCsn5 distributed in two fractions include holo-complex and monomeric form, whereas knockdown of EsCsn5 has little impact on the amount of the holo-complex. EsCsn5 was widely expressed in different crab tissues, while its expression was significantly reduced upon bacterial infection. Crab hemocytes showed significantly enhanced proliferation when EsCsn5 was genetically knocked down, suggesting a critical role for CSN5 in the negative regulation of crab hemocyte proliferation. Moreover, EsCSN5 but not the EsCSN8 was demonstrated to negatively regulate the early G1 phase of the cell cycle by controlling the degradation of EsCyclin E through ubiquitination steps, rather than affecting its transcription. Furthermore, in the EsCyclin E-suppressed crab there was a significantly reduced survival rate and an up-regulated hemolymph bacterial concentration. Taken together, this study provides evidence demonstrating that invertebrate hemocytes down-regulate the expression of EsCsn5 upon bacterial challenge, thus promoting proliferation in an EsCyclin E-dependent manner in order to protect the crab from infection.

Down Syndrome Cell Adhesion Molecule Triggers Membrane-to-Nucleus Signaling-Regulated Hemocyte Proliferation against Bacterial Infection in Invertebrates.

Down syndrome cell adhesion molecule (Dscam) generates tens of thousands of isoforms by alternative splicing, thereby providing crucial functions during immune responses. In this study, a novel Dscam signaling pathway was investigated in crab, which remains poorly characterized in invertebrates. Bacterial infection induced the cytoplasmic cleavage of Dscam intracellular domains (ICDs) by γ-secretase, and then the released ICDs carrying specific alternatively spliced exons could directly interact with IPO5 to facilitate nuclear translocation. Nuclear imported ICDs thus promoted hemocyte proliferation and protect the host from bacterial infection. Protein-interaction studies revealed that the ectodomain of Dscam bound to a disintegrin and metalloprotease domain 10 (ADAM10) rather than ADAM17. Inhibition or overexpression of ADAM10 impaired or accelerated Dscam shedding activity post-bacterial stimulation, respectively. Moreover, the shedding signal then mediated Dscam with an intact cytoplasmic domain to promote the cleavage of ICDs by γ-secretase. Furthermore, the transcription of ADAM10 was regulated by Dscam-induced canonical signaling, but not nuclear imported ICDs, to serve as a feedback regulation between two different Dscam pathways. Thus, membrane-to-nuclear signaling of Dscam regulated hemocyte proliferation in response to bacterial infection.

An ancient interleukin-16-like molecule regulates hemocyte proliferation via integrin ß1 in invertebrates.

Interleukins (ILs) are cytokines with crucial functions in innate and adaptive immunity. IL genes are only found in vertebrates, except for IL-16, which has been cloned in some arthropod species. However, the function of this gene in invertebrates is unknown. In the present study, an IL-16-like gene (EsIL-16) was identified from the Chinese mitten crab Eriocheir sinensis. EsIL-16 was predicted to encode a precursor (proEsIL-16) that shares similarities with pro-IL-16 proteins from insects and vertebrates. We show that caspase-3 processes proEsIL-16 into an approximately 144-kDa N-terminal prodomain with nuclear import activity and an approximately 34-kDa mature peptide that might be secreted into the extracellular region. EsIL-16 mRNA could be detected in all analyzed tissues and was significantly upregulated after immune challenge both in vitro and in vivo. T7 phage display library screening suggested potential binding activity between EsIL-16 and integrin, which was confirmed by coimmunoprecipitation assay. Interestingly, EsIL-16 promoted cell proliferation via integrin ß1 in primary cultured crab hemocytes and Drosophila S2 cells. Furthermore, the interaction between EsIL-16 and integrin ß1 was necessary to efficiently protect the host from bacterial infection. To our knowledge, this study revealed integrin ß1 as a receptor for IL-16 and the function of this interaction in hemocyte proliferation in invertebrates for the first time. These results provide new insights into the regulation of innate immune responses in invertebrates and shed the light on the evolution of ILs within the animal kingdom.