IBV QX affects the antigen presentation function of BMDCs through nonstructural protein16.

The gamma-coronavirus infectious bronchitis virus (IBV) has a high mutation rate and mainly invades the respiratory mucosa, making it difficult to prevent and causing great economic losses. Nonstructural protein 16 (NSP16) of IBV QX also not only plays an indispensable role in virus invading but also might hugely influence the antigen's recognition and presentation ability of host BMDCs. Hence, our study tries to illustrate the underline mechanism of how NSP16 influences the immune function of BMDCs. Initially, we found that NSP16 of the QX strain significantly inhibited the antigen presentation ability and immune response of mouse BMDCs, which was stimulated by Poly (I:C) or AIV RNA. Besides mouse BMDCs, we also found that NSP16 of the QX strain also significantly stimulated the chicken BMDCs to activate the interferon signaling pathway. Furthermore, we preliminarily demonstrated that IBV QX NSP16 inhibits the antiviral system by affecting the antigen-presenting function of BMDCs.

Effects of modified external ventricular drainage vs. an Ommaya reservoir in the management of hydrocephalus with intracranial infection in pediatric patients.

Background: Hydrocephalus with intracranial infection (HII) may cause pathological changes in brain tissue structure and irreversible damage to the nervous system. However, intracranial infection is a contraindication to ventriculo-peritoneal (VP) shunt surgery, and the prognosis is improved by early infection control and intracranial pressure reduction. This study evaluated the safety and efficacy of the Ommaya reservoir vs. modified external ventricular drainage (M-EVD) in the management of HII in pediatric patients. Methods: This retrospective controlled study included 45 pediatric patients with HII treated with an Ommaya reservoir (n = 24) or M-EVD (n = 21) between January 2018 and December 2022. Clinical outcomes, cerebrospinal fluid (CSF) test results, complications, and outcomes were compared between the Ommaya reservoir and M-EVD groups. Results: No patient died during the follow-up period. The two groups were similar regarding age, sex, admission temperature, weight, preoperative serum protein and albumin concentrations, CSF analysis (white blood cell count, glucose concentration, and protein content), and clinical symptoms (P > 0.05). Both groups had significant changes in the CSF test results postoperatively compared with preoperatively (P < 0.05). In the M-EVD group, the median days for 13 children to remove the external drainage tube and receive VP shunt was 19 days. The longest drainage tube retention time was 61 days, and there was no intracranial infection or serious complication related to the drainage tube. After the placement of the Ommaya, the median time required for CSF to return to normal was 21 days, and a total of 15 patients underwent VP shunt surgery. Conclusion: The Ommaya reservoir and M-EVD are safe and effective for pediatric patients with HII. Both methods reduce the intracranial pressure and alleviate the symptoms of hydrocephalus, although there are differences between the two methods.

Impact of therapy on cancer metabolism in high-risk localized prostate cancer treated with neoadjuvant docetaxel and androgen deprivation therapy.

BACKGROUND: The application of neoadjuvant docetaxel and androgen deprivation therapy before radical prostatectomy has been clinically recognized as beneficial for the overall and progression-free survival of patients with advanced prostate cancer. However, the mechanism underlying its clinical efficacy has not yet been reported. METHODS: We conducted a randomized comparative study on about 100 patients with high-risk localized prostate cancer. Through nontarget metabolomics and tissue microarray immunohistochemistry, we investigated the difference in the endogenous metabolism of tumors in patients with prostate cancer who received or did not receive the neoadjuvant therapy. RESULTS: Many endogenous metabolic pathways, especially nucleotide synthesis, glutathione metabolism, citric acid cycle, and lipid synthesis, in prostate cancer tissue were altered after the neoadjuvant treatment, and the levels of nearly 90% of the differentially regulated metabolites were significantly decreased. Moreover, the levels of key enzymes in the cellular energy pathways were downregulated in tumor tissues and upregulated in adjacent tissues after the treatment. The positive and negative effects of the neoadjuvant therapy on normal and tumor cells in the prostate, respectively, resulted in the activation of the former and inhibition of the latter, which helped in reducing the number of tumors and weakened their aggressiveness. CONCLUSIONS: From the perspective of endogenous metabolism in tumors, we have confirmed that neoadjuvant therapy can significantly downregulate important pathways for biosynthesis and energy metabolism in prostate cancer tissue, and thereby, inhibit tumor growth and metastasis.

Metabolomic profiling to evaluate the efficacy of proxalutamide, a novel androgen receptor antagonist, in prostate cancer cells.

Proxalutamide is a newly developed androgen receptor (AR) antagonist for the treatment of castration-resistant prostate cancer (PCa) that has entered phase III clinical trials. In the present study, we intended to elucidate the antitumor efficacy of proxalutamide through the metabolomic profiling of PCa cells. Two AR-positive PCa cell lines and two AR-negative PCa cell lines were investigated. Cell viability assays based on ATP quantitation were conducted. LC-Q/TOF-MS was used to analyze intracellular metabolites before or after the administration of proxalutamide and two other clinical AR antagonists (bicalutamide and enzalutamide). The results of this study showed that the inhibitory effect of proxalutamide on PCa cell proliferation was better than that of bicalutamide and enzalutamide, and proxalutamide preferentially affected AR-positive PCa cells over AR-negative cells. The metabolic composition of PCa cells changed significantly after proxalutamide administration, and these changes in response to proxalutamide were significantly different from those in the presence of the two other AR antagonists. In AR-positive cells, proxalutamide significantly decreased the intracellular levels of glutamine, glutamate, glutathione, cysteine, glycine, aspartate, uridine, cytidine and thymidine. However, the effects of the two other antagonists on these discriminant metabolites were ambiguous, and no changes in these metabolites were found in AR-negative cells. Our findings indicate that proxalutamide has inhibitory effects on glutamine metabolism, redox homeostasis and de novo pyrimidine synthesis in AR-positive PCa cells that enhance the cellular sensitivity to proxalutamide.