PAK1 Promotes Inflammation Induced by Sepsis through the Snail/CXCL2 Signaling Pathway.

Sepsis is a severe syndrome characterized by organ dysfunction, resulting from a systemic imbalance in response to infection. PAK1 plays a critical role in various diseases. The present study aimed to explore and delineate the mechanism of PAK1 in inflammation induced by sepsis. Bioinformatics analysis was performed to assess PAK1, snail, and CXCL2 expression in the whole blood of septic patients and the pathways enriched with PAK1. To simulate the sepsis model, THP-1 cells were stimulated with lipopolysaccharide. Gene expression was evaluated using qRT-PCR, while cell viability was assessed using CCK-8 assay. Cell apoptosis was tested with flow cytometry. Expression of inflammatory factors in cells following different treatments was analyzed using the enzyme linked immunosorbent assay (ELISA). Dual-luciferase and chromatin immunoprecipitation assays were conducted to verify the binding relationship between PAK1 and the snail. Mouse models of cecal ligation and puncture were established, and hematoxylin and eosin staining and ELISA were employed to detect the infiltration levels of inflammatory cells and the expression of related protective factors in lung, liver, and kidney tissues. The results demonstrated upregulation of PAK1, snail, and CXCL2 in the whole blood of septic patients, with PAK1 being enriched in the chemokine-related pathway. Knockdown of PAK1 significantly promoted the apoptosis of LPS-stimulated THP-1 cells and inhibited the expression of inflammatory factors. PAK1 upregulated the expression of the snail, which in turn promoted the expression of CXCL2. Thus, PAK1 mediated the sepsis-induced inflammatory response through the snail/CXCL2 pathway. In conclusion, PAK1 played a role in promoting inflammation induced by sepsis through the snail/CXCL2 axis, thereby providing a potential therapeutic target for the management of sepsis.

TCF7 and LEF-1 downregulation in sepsis promotes immune suppression by inhibiting CD4+ T cell proliferation.

BACKGROUND: Previous studies have shown that sepsis is implicated in a reduction in the number and function of CD4+ T cells. TCF7 and LEF-1 facilitate early T cell development and lineage selection of CD4+ T cells. However, the function and mechanism of TCF7 and LEF-1 in sepsis are uncharacterized. This study intended to delineate effect of TCF7 and LEF-1 on sepsis and the impact on proliferation of CD4+ T cells in sepsis. METHODS: A mouse sepsis model was constructed by cecal ligation and puncture (CLP) method. Expression of TCF7 and LEF-1 in sepsis was investigated using bioinformatics analysis and molecular experiments. We then constructed TCF7 and LEF-1 overexpression cell lines to investigate their effects on proliferation, apoptosis, effector activation, and immunosuppressive molecules of CD4+ T cells in sepsis. RESULTS: TCF7 and LEF-1 were downregulated in sepsis. As the duration of sepsis induction increased, the levels of TCF7 and LEF-1 gradually decreased, as did the number of CD4+ T cells. Cell experiments showed that overexpression of TCF7 and LEF-1 enhanced proliferation and effector activation of CD4+ T cells, reduced apoptosis, decreased PD-1 and LAG3 expression, and promoted immune response in sepsis. CONCLUSION: In conclusion, this study confirmed that downregulation of TCF7 and LEF-1 expression in sepsis inhibited proliferation of CD4+ T cells, leading to immune suppression. This finding suggested that TCF7 and LEF-1 were potential biological targets for sepsis and indicated that immunotherapy aimed at improving CD4+ T cell proliferation may be a new strategy for immune therapy in sepsis patients.

Recurrent generalized seizures as the prominent manifestation in a patient with CADASIL: a case report and literature review.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited arteriopathy typically caused by mutations in the NOTCH-3 gene. Few detailed descriptions of recurrent generalized seizures in CADASIL has been reported. CASE PRESENTATION: This article details a case of recurrent generalized seizures, which eventually be diagnosed as CADASIL with a heterozygous variant, c.1630 C > T (p. Arg544Cys), in exon 11 of the Notch 3 gene. Here, we discussed the possible pathogenesis underlying the epilepsy associated with CADASIL through the brain magnetic resonance imaging changes and the captured epileptiform waves in the electroencephalography during the patient's follow-up period. Related literatures were also reviewed to discuss the etiology of the epilepsy. CONCLUSIONS: Recurrent generalized seizures may be a presenting neurological manifestation of CADASIL in the absence of other discernible causes. Clinicians should comprehensively seek the possible etiology of patients with recurrent generalized seizures, considering the possible diagnosis of CADASIL.

Detection and analysis of clinical features of patients with different types of coronavirus disease 2019.

This study was designed to investigate the change of various indexes in patients with different types of coronavirus disease 2019 (COVID-19). Seventy-five patients with COVID-19 were collected from the First Affiliated Hospital, Zhejiang University School of Medicine, and they were classified into moderate, severe and critically severe types according to the disease severity. The basic information, blood routine, pneumonia-related blood indexes, immune-related indexes along with liver, kidney and myocardial indexes in patients with different types were analyzed. The analysis of immune-related indexes showed that the proportions of critically severe patients with abnormal interleukin-2 (IL-2) and IL-4 were higher than those of severe and moderate patients. In addition, the proportion of patients with abnormal total cholesterol increased as the severity of disease increased, and the proportion in critically severe patients was significantly higher than that in moderate patients. The patients with a more severe COVID-19 are older and more likely to have a history of hypertension. With the progression of COVID-19, the abnormal proportion of total white blood cell, neutrophils, lymphocytes, IL-2, IL-4, and total cholesterol increased. The change of these indexes in patients with different COVID-19 types could provide reference for the disease severity identification and diagnosis of COVID-19. In addition, the change in the total cholesterol level suggested that COVID-19 would induce some liver function damage in patients.

Automatic spectral calibration for polarization-sensitive optical coherence tomography.

Accurate wavelength assignment is important for Fourier domain polarization-sensitive optical coherence tomography. Incorrect wavelength mapping between the orthogonal horizontal (H) and vertical (V) polarization channels leads to broadening the axial point spread function and generating polarization artifacts. To solve the problem, we propose an automatic spectral calibration method by seeking the optimal calibration coefficient between wavenumber kH and kV. The method first performs a rough calibration to get the relationship between the wavelength λ and the pixel number x of the CCD for each channel. And then a precise calibration is taken to bring both polarization interferograms in the same k range through the optimal calibration coefficient. The optimal coefficient is automatically obtained by evaluating the cross-correlation of A-line signals. Simulations and experiments are implemented to demonstrate the performance of the proposed method. The results show that, compared to the peaks method, the proposed method is suitable in both Gaussian and non-Gaussian spectrums with a higher calibration accuracy.

Depth-dependent dispersion compensation for full-depth OCT image.

A depth-dependent dispersion compensation algorithm for enhancing the image quality of the Fourier-domain optical coherence tomography (OCT) is presented. The dispersion related with depth in the sample is considered. Using the iterative method, an analytical formula for compensating the depth-dependent dispersion in the sample is obtained. We apply depth-dependent dispersion compensation algorithm to process the phantom images and in vivo images. Using sharpness metric based on variation coefficient to compare the results processed with different dispersion compensation algorithms, we find that the depth-dependent dispersion compensation algorithm can improve image quality at full depth.