Neutrophils exert protection in early Aeromonas veronii infections through the clearance of both bacteria and dying macrophages.

Aeromonas veronii is a gram-negative opportunistic pathogen capable of infecting both fish and mammals. Left untreated, natural infection in fish can prove fatal and result in irreparable damage to the aquaculture industry. Neutrophils are essential innate effector cells that play critical roles in pathogen defense. Our aim was to investigate the immunological roles of teleost neutrophils during infection with A. veronii. We began by examining the functional defenses of neutrophils in vitro, where neutrophils efficiently killed the pathogen. In addition, we developed an in vivo infection model to assess the roles of neutrophils during an infection in goldfish. This allowed us to explore the complex dynamics between immune cells and Aeromonas veronii. Interestingly, our studies found that neutrophils are capable of sensing a diverse range of dead and dying cells, resulting in varying downstream responses. Herein, we report that neutrophils internalized dead or dying macrophages previously infected with A. veronii. Moreover, once internalized, neutrophils went on to display classical pro-inflammatory ROS responses, in contrast to the more typical anti-inflammatory responses seen in cells following the uptake of a dead host cell. This led us to hypothesize that during infection, neutrophils are capable of simultaneously clearing dead and dying cells as well as A. veronii. This study provides additional insights into the complex mechanisms by which neutrophils operate within an inflammatory site and contribute to the induction and regulation of acute inflammatory responses.

Capillary Flow Rates in the Duodenum of Pediatric Ulcerative Colitis Patients Are Increased and Unrelated to Inflammation.

BACKGROUND AND AIM: Inflammatory bowel diseases (IBD), including Crohn disease (CD) and ulcerative colitis (UC), are chronic pediatric disorders. Changes in vasculature are described in IBD, but these could be secondary to inflammation and the role in pathogenesis is poorly understood. Assessing circulatory changes in typically unaffected sites in IBD (eg, duodenum), when inflammation is absent, can identify vascular changes associated with pathogenesis. The aim of the study is to measure capillary flow rates in duodenal mucosa using probe-based confocal laser endomicroscopy (pCLE) during endoscopy in children with IBD. METHODS: Images of villi with visible blood vessels obtained using pCLE were captured as video sequences. Capillary flow rate (mm/s) was calculated by dividing the distance travelled by blood cells by the duration of the sequence. Flow rates were correlated with various clinical parameters. RESULTS: Forty-five patients (22 non-IBD, 14 CD, 9 UC) were included in the study. Duodenal capillary flow rates were significantly higher in UC patients (0.75 ±â€Š0.07 mm/s) as compared to non-IBD (0.57 ±â€Š0.03) and CD (0.65 ±â€Š0.04). There was no correlation between serum hemoglobin and albumin, disease activity indices, serum inflammatory markers, and capillary flow rates in patients. CONCLUSIONS: This pilot study shows, for the first time, increased capillary blood flow in the duodenum of UC patients that was unrelated to inflammatory markers or disease activity. Thus, early vascular changes can be assessed using pCLE during endoscopy.

Acute Kidney Allograft Rejection Following Coronavirus mRNA Vaccination: A Case Report.

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The physical interaction of p53 and plakoglobin is necessary for their synergistic inhibition of migration and invasion.

Plakoglobin (PG) is a paralog of ß-catenin with similar adhesive, but contrasting signalling functions. Although ß-catenin has well-known oncogenic function, PG generally acts as a tumor/metastasis suppressor by mechanisms that are just beginning to be deciphered. Previously, we showed that PG interacted with wild type (WT) and a number of mutant p53s, and that its tumor/metastasis suppressor activity may be mediated, at least partially, by this interaction. Here, carcinoma cell lines deficient in both p53 and PG (H1299), or expressing mutant p53 in the absence of PG (SCC9), were transfected with expression constructs encoding WT and different fragments and deletions of p53 and PG, individually or in pairs. Transfectants were characterized for their in vitro growth, migratory and invasive properties and for mapping the interacting domain of p53 and PG. We showed that when coexpressed, p53-WT and PG-WT cooperated to decrease growth, and acted synergistically to significantly reduce cell migration and invasion. The DNA-binding domain of p53 and C-terminal domain of PG mediated p53/PG interaction, and furthermore, the C-terminus of PG played a central role in the inhibition of invasion in association with p53.