The aim of the research was to investigate the antiviral and immunoregulatory effects of saikosaponin A, saikosaponin D, Panax notoginseng saponins, notoginsenoside R1, and anemoside B4 saponins commonly found in Chinese herbal medicines.control mice were challenged intramuscularly (im) with 0.2 mL of porcine circovirus 2 (PCV2) solution containing 107 TCID50 of the virus/mL. Mice of high-, middle-, and low-dose saponin groups were initially challenged im with 0.2 mL of PCV2 solution and three days later treated intraperitoneally (ip) with one of five saponins at one of three doses (10, 5, or 1 mg/kg b.w.). In the drug control group, mice were dosed ip with 10 mg/kg b.w. of a given saponin, and mice in a blank control group were administered the same volume of normal saline.The results revealed that the saponins could reduce the incidence and severity of PCV2-induced immunopathological damage, e.g. body temperature elevation, weight loss, anaemia, and internal organ swelling. In addition, it was seen that the saponins could affect the immunoglobulin levels and protein absorption.The data suggested that the saponins might effectively regulate immune responses.
Objective: 18F-FDG PET can directly reflect the glucose metabolism level of cells from the molecular level. Tumor-associated fibroblasts, as the natural physiological barrier of tumors, support and protect the survival of non-small cell lung cancer cells. This study will further observe the differences in the supporting effects of CAFs from different regions of 18F-FDG PET metabolism on cancer cells. Methods: Biopsy tissues were collected from PET/CT patients diagnosed with NSCLC for the first time in the Department of Nuclear Medicine, The First Hospital of Shanxi Medical University. The locations of puncture were all selected in areas with high metabolism of tumor. Primary CAFs were cultured by tissue adhesion method. A549 acts as EGFR (-) tumor cells, while PC9 acts as EGFR (+) tumor cells. CAFs conditional medium was collected to induce the culture of A549 and PC9 cells, labeled as A549high/low and PC9high/low, respectively. CCK was used to measure cancer cell proliferation rate, Transwell was used to measure cancer cell invasiveness, and scratch assay was used to measure cancer cell migration. The cells were treated with cisplatin and gefitinib respectively to observe the resistance of the cells. Results: Tissues of two NSCLC patients with SUVmax were 1.25 and 11.15, respectively. The conditioned medium induced cancer cells for 48 hours. CCK (48h) results showed that SUVhigh-derived CAFs could promote the proliferation of two types of cancer cells more than SUVlow-derived CAFs. The wound healing experiment showed that A549high had completed the healing at 72h, followed by low metabolism area, and A549 was the worst. The results for PC9 cells were similar to those for A549. Transwell experiment showed that PC9high/ low showed obvious difference in invasiveness at 24 hours, and the difference was more significant at 48 hours. A549 also showed difference in invasiveness, but the difference was relatively weak. When the corresponding cells were further treated with cisplatin or gefitinib, the proliferation rate of A549high/low cells was significantly different in the gradient range of high cisplatin concentration, while the proliferation rate of PC9high/low cells was significantly different in the low-medium gefitinib concentration. Conclusion: The regions of FDG metabolism difference shown in PET support the reverse warburg effect. As a physiological barrier to tumors, CAFs is one of the key factors that promote the occurrence, metastasis and drug resistance of lung cancer. National Natural Science Foundation of China (Grant number:81971655) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Porcine circovirus-like virus P1 is an important pathogen of the current pig industry, the infection mechanism is not entirely clear. Wnt signaling pathway plays an important role in the growth of young animals and infection of some viruses. This study was designed to demonstrate the effects of P1 infection on the Wnt signaling pathway. In vivo experiments, we demonstrated the down-regulatory effects of P1 infection in piglets and mice on the downstream components expression levels of Wnt signaling pathway, and the effects of Wnt signaling pathway activation on the pathogenesis of P1. In vitro studies, we found P1 infection down-regulated protein level of β-catenin and mRNA level of mmp2, prevented the β-catenin from entering into nucleus, abolished the TCF/LEF promoter activity, proved that P1 could inhibit the activation of Wnt signaling pathway in vitro. Finally, we found that VP1 of P1 virus also had the inhibitory effects on Wnt signaling pathway in vitro, elucidated the mechanism of P1's inhibitory effects on the Wnt signaling pathway and offered the possibility that the suppression of Wnt signaling pathway was involved in the post-weaning multisystemic wasting syndrome (PMWS), laying a foundation for elucidating the pathogenesis of P1.
Introduction Multiplexed PET imaging revolutionized clinical decision-making by simultaneously capturing various radiotracer data in a single scan, enhancing diagnostic accuracy and patient comfort. Through a transformer-based deep learning, this study underscores the potential of advanced imaging techniques to streamline diagnosis and improve patient outcomes. Patients and Methods The research cohort consisted of 120 patients spanning from cognitively unimpaired individuals to those with mild cognitive impairment, dementia, and other mental disorders. Patients underwent various imaging assessments, including 3D T1-weighted MRI, amyloid PET scans using either 18 F-florbetapir (FBP) or 18 F-flutemetamol (FMM), and 18 F-FDG PET. Summed images of FMM/FBP and FDG were used as proxy for simultaneous scanning of 2 different tracers. A SwinUNETR model, a convolution-free transformer architecture, was trained for image translation. The model was trained using mean square error loss function and 5-fold cross-validation. Visual evaluation involved assessing image similarity and amyloid status, comparing synthesized images with actual ones. Statistical analysis was conducted to determine the significance of differences. Results Visual inspection of synthesized images revealed remarkable similarity to reference images across various clinical statuses. The mean centiloid bias for dementia, mild cognitive impairment, and healthy control subjects and for FBP tracers is 15.70 ± 29.78, 0.35 ± 33.68, and 6.52 ± 25.19, respectively, whereas for FMM, it is −6.85 ± 25.02, 4.23 ± 23.78, and 5.71 ± 21.72, respectively. Clinical evaluation by 2 readers further confirmed the model's efficiency, with 97 FBP/FMM and 63 FDG synthesized images (from 120 subjects) found similar to ground truth diagnoses (rank 3), whereas 3 FBP/FMM and 15 FDG synthesized images were considered nonsimilar (rank 1). Promising sensitivity, specificity, and accuracy were achieved in amyloid status assessment based on synthesized images, with an average sensitivity of 95 ± 2.5, specificity of 72.5 ± 12.5, and accuracy of 87.5 ± 2.5. Error distribution analyses provided valuable insights into error levels across brain regions, with most falling between −0.1 and +0.2 SUV ratio. Correlation analyses demonstrated strong associations between actual and synthesized images, particularly for FMM images (FBP: Y = 0.72X + 20.95, R 2 = 0.54; FMM: Y = 0.65X + 22.77, R 2 = 0.77). Conclusions This study demonstrated the potential of a novel convolution-free transformer architecture, SwinUNETR, for synthesizing realistic FDG and FBP/FMM images from summation scans mimicking simultaneous dual-tracer imaging.
Background: This study aimed to investigate the effect and mechanism of gambogic acid (GA) on the apoptosis and inflammation of human retinal endothelial cells (HRECs) under high glucose conditions.
Triggering receptor expressed on myeloid cells 1 (TREM-1) plays a vital role in the pathogen-triggered amplification loop required for proinflammatory responses. Blockade of TREM-1 signaling may inhibit expansion of sepsis and prolong survival of animals. In the present study, the gene of porcine soluble TREM-1 was cloned and expressed in E. coli. After purification, the bioactivity of recombinant porcine soluble TREM-1 was tested in vitro on porcine alveolar macrophages. The results showed that supplementation with the recombinant porcine sTREM-1 protein rapidly and dose-dependently attenuated the upregulation of cytokines (IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12, IL-16, IL-18, and TNF-α) caused by LPS stimulation in the cultured porcine alveolar macrophages. These results indicate that the recombinant porcine sTREM-1 protein can prevent TREM-1-mediated hyperinflammatory responses after exposure to LPS.
The aim of this study was to investigate the anti-endotoxin effects of sinomenine, fangchinoline, stachydrine, chuanxionggzine, oxymartrine and evodiamine alkaloids commonly found in Chinese herbal medicines. Porcine endothelial cells were challenged with 1 μg LPS/ml for 3 h and then treated with one of the six alkaloids at three concentrations (1, 5 or 10 μg/ml) for a further 21 h. The supernatants of the cultures were then collected and analyzed for levels of nitric oxide (NO), interleukin (IL)-10, intercellular cell adhesion molecule-1 (ICAM-1) and IL-2 using ELISA kits. The results revealed that sinomenine, stachydrine and chuanxionggzine inhibited production of NO; stachydrine and evodiamine inhibited secretion of IL-10; sinomenine and chuanxionggzine down-regulated ICAM-1 expression; oxymartrine and evodiamine decreased production of IL-2 by the LPS-stimulated endothelial cells. Overall, the data from these studies suggested to us that these six alkaloids might effectively reduce inflammatory responses in situ via changes in the formation of these key regulatory molecules/proteins.
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