Aspirin inhibits rotavirus replication and alters rat gut microbial composition.

BACKGROUND: Aspirin is widely used to treat various clinical symptoms. Evidence suggests that aspirin has antiviral properties, but little is known about its specific effect against rotavirus. METHODS: MA104, Caco-2, and CV-1 cells were infected with rotavirus, and aspirin was added after 12 h. Viral mRNA and titer levels were measured by qRT-PCR and immunofluorescence assays. For in vivo validation, forty specific-pathogen-free SD rats were randomly divided into oral aspirin (ASP) groups and control (NC) groups. 16 S rRNA gene sequencing was performed to identify gut microbiota. After 6 months of continuous ASP/NC administration, the rats were infected with rotavirus. Fecal samples were collected over a 30-day time course, and viral levels were quantified. Proinflammatory cytokines/chemokine levels were measured by ELISA. RESULTS: Aspirin inhibited rotavirus infection in cell lines and in rats. The effects of aspirin on viral replication were associated with the alteration of gut microbiota composition by aspirin, including increased abundance of Firmicutes and decreased abundance of Bacteroidetes after aspirin treatment. Mechanistically, aspirin reduced IL-2 and IL-10 levels, and increased IRF-1 and COX-2 levels. Aspirin blocked rotavirus replication in vitro and in vivo, which might be related to effects on IRF-1, COX-2, chemokines, and gut microbial composition. CONCLUSION: These results indicate that long-term oral aspirin administration reduces rotavirus infection. Intestinal virus infection may be suppressed in elderly patients who take aspirin for a long time. The change of their Gut microbiota may lead to functional disorder of the intestinal tract, which may provide some reference for clinical adjuvant probiotics treatment.

Protective effects of methylprednisolone-cyclophosphamide treatment on bleomycin-induced pulmonary fibrosis.

BACKGROUND: Methylprednisolone (MP) and cyclophosphamide (CTX) combination treatment has shown great benefits in improving pulmonary fibrosis (PF) and high safety. Currently, the mechanism underlying the effects of MP-CTX on improving PF remains unclear. This study determined the effects of MP-CTX combination treatment on the modulation of inflammation, oxidative stress, and T-cell immunity in PF. METHODS: PF rat models were induced by bleomycin stimulation. MP (3 mg/kg) and MP-CTX (MP: 3 mg/kg; CTX: 8 mg/kg) combination were administered in the PF + MP and PF + MP + CTX groups, respectively. Transmission electron microscopy, hematoxylin and eosin staining, Ashcroft score, and Masson trichrome staining were performed to measure lung morphology in PF. Enzyme-linked immunosorbent assay and quantitative polymerase chain reaction assay were performed to quantify inflammatory factors. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) levels were determined using commercial kits. α-Smooth muscle actin (SMA) and collagen I levels were determined using western blotting and immunohistochemistry. The T-cell count was evaluated using flow cytometry. RESULTS: MP-CTX reduced lung injury, collagen deposition, and α-SMA and collagen I levels in a bleomycin-induced PF rat model. Additionally, MP-CTX decreased the levels of MDA and inflammatory factors (tumor necrosis factor-α, interleukin-1ß, and interleukin-6) but increased the activities of SOD and GSH-PX. Furthermore, MP-CTX changed T-cell types in lung tissues, such as increasing CD4+CD25+Foxp3+ cell count. CONCLUSIONS: MP-CTX combination treatment improved the degree of PF by reducing inflammation and oxidative stress and improving T-cell immunity. These findings provide novel insights into the mechanisms underlying the effects of MP-CTX on PF.

Appropriate empirical antifungal therapy is associated with a reduced mortality rate in intensive care unit patients with invasive fungal infection: A real-world retrospective study based on the MIMIC-IV database.

Objective: The study aimed to determine the prevalence and pathogens of invasive fungal infection (IFI) among intensive care unit (ICU) patients. The next goal was to investigate the association between empirical antifungal treatment and mortality in ICU patients. Methods: Using microbiological events, we identified all ICU patients with IFI and then retrieved electronic clinical data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The data were statistically analyzed using t-tests, chi-square tests, log-rank tests, and Cox regression. Results: The most commonly reported fungi were Candida (72.64%) and Aspergillus (19.08%). The most frequently prescribed antifungal medication was fluconazole (37.57%), followed by micafungin (26.47%). In the survival study of ICU patients and patients with sepsis, survivors were more likely to receive empirical antifungal treatment. In contrast, non-empirical antifungal therapy was significantly associated with poor survival in patients with positive blood cultures. We found that the current predictive score makes an accurate prediction of patients with fungal infections challenging. Conclusions: Our study demonstrated that empirical antifungal treatment is associated with decreased mortality in ICU patients. To avoid treatment delays, novel diagnostic techniques should be implemented in the clinic. Until such tests are available, appropriate empirical antifungal therapy could be administered based on a model that predicts the optimal time to initiate antifungal therapy. Additional studies should be conducted to establish more accurate predictive models in the future.

AQP9 and ZAP70 as immune-related prognostic biomarkers suppress proliferation, migration and invasion of laryngeal cancer cells.

BACKGROUND: Laryngeal cancer represents a common malignancy that originates from the larynx, with unfavorable prognosis. Herein, this study systematically analyzed the immune signatures of laryngeal cancer and to evaluate their roles on tumor progression. METHODS: Differentially expressed immune-related genes (IRGs) were screened between laryngeal cancer and normal tissues from TCGA dataset. Then, two prognosis-related IRGs AQP9 and ZAP70 were analyzed by a series of survival analysis. Based on them, molecular subtypes were constructed by unsupervised cluster analysis. Differences in survival outcomes, HLA expression and immune cell infiltrations were assessed between subtypes. Expression of AQP9 and ZAP70 was validated in laryngeal cancer tissues and cells by RT-qPCR and immunohistochemistry. After silencing and overexpressing AQP9 and ZAP70, CCK-8, EdU, wound healing and transwell assays were performed in TU212 and LCC cells. RESULTS: Totally, 315 IRGs were abnormally expressed in laryngeal cancer. Among them, AQP9 and ZAP70 were distinctly correlated to patients' prognosis. Two subtypes were developed with distinct survival outcomes, HLA expression and immune microenvironment. Low expression of AQP9 and ZAP70 was confirmed in laryngeal cancer. AQP9 and ZAP70 up-regulation distinctly suppressed proliferation, migration, and invasion of laryngeal cancer cells. The opposite results were investigated when their knockdown. CONCLUSIONS: Our findings revealed the roles of AQP9 and ZAP70 in progression of laryngeal cancer, and suggested that AQP9 and ZAP70 could potentially act as candidate immunotherapeutic targets for laryngeal cancer.

Thrombocytopenia in 737 adult intensive care unit patients: A real-world study of associated factors, drugs, platelet transfusion, and clinical outcome.

OBJECTIVE: We aimed to identify and represent factors associated with thrombocytopenia in intensive care unit, especially the pathogens and drugs related to severe and extremely thrombocytopenia. Then, we aim to compare the mortality of platelet transfusion and non-transfusion in patients with different degrees of thrombocytopenia. METHODS: We identified all thrombocytopenic patients in intensive care unit by using platelet-specific values and then extracted electronic health records from our Hospital Information System. Data were statistically analyzed with t test, chi-square test, and logistic regression. RESULTS: We found that infections (32.7%) were the most frequent cause associated with thrombocytopenia, followed by sepsis shock (3.93%) and blood loss (2.99%). Meanwhile, antifungals (p = 0.002) and bacterial infection (p = 0.037) were associated with severe and extremely severe thrombocytopenia. Finally, we found that the mortality of platelet transfusion and non-transfusion in patients was statistically significant for patients with platelet counts between 30 and 49/nL (χ2 = 9.719, p = 0.002). CONCLUSION: Infection and sepsis emerged as two primary factors associated with thrombocytopenia in intensive care unit. Meanwhile, antifungals and bacterial infection were associated with platelet counts less than 49/nL. Finally, platelet transfusion may be associated with reduced mortality in patients with platelet counts between 30 and 49/nL.

Chrysophanol inhibits proliferation and induces apoptosis through NF-κB/cyclin D1 and NF-κB/Bcl-2 signaling cascade in breast cancer cell lines.

Chrysophanol is an anthraquinone compound, which exhibits anticancer effects on certain types of cancer cells. However, the effects of chrysophanol on human breast cancer remain to be elucidated. The aim of the present study was to clarify the role of chrysophanol on breast cancer cell lines MCF­7 and MDA­MB­231, and to identify the signal transduction pathways regulated by chrysophanol. MTT assay and flow cytometric analysis demonstrated that chrysophanol inhibited cell proliferation, and cell cycle progression in a dose­dependent manner. The expression of cell cycle­associated cyclin D1 and cyclin E were downregulated while p27 expression was upregulated following chrysophanol treatment at the mRNA, and protein levels. The Annexin V/propidium iodide staining assay results revealed that apoptosis levels increased following chrysophanol treatment. Chrysophanol upregulated caspase 3 and poly (ADP­ribose) polymerase cleavage in both cell lines. Furthermore, chrysophanol enhanced the effect of paclitaxel on breast cancer cell apoptosis. In addition, chrysophanol downregulated apoptosis regulator Bcl­2 protein, and transcription factor p65 and IκB phosphorylation. Inhbition of nuclear factor (NF)­κB by ammonium pyrrolidine dithiocarbamate diminished the effect of chrysophanol on apoptosis and associated proteins. In conclusion, the results of the current study demonstrated that chrysophanol effectively suppresses breast cancer cell proliferation and facilitates chemosentivity through modulation of the NF-κB signaling pathway.

Memantine attenuates the impairment of spatial learning and memory of pentylenetetrazol-kindled rats.

Cognitive disorders after epilepsy can have a great impact on the quality of life of epileptic patients, though it has not drawn much attention. Even after identified, it is often undertreated or has gone untreated. Memantine has been approved to treat moderate to severe Alzheimer disease (AD), which is characterized by cognitive impairment. In present study, we determined the effects of memantine on PTZ-kindled rats, which can mimic the postseizure dysfunction that resembles symptoms observed in human epilepsy. We found that memantine can ameliorate the spatial learning and memory of epileptic rats. But contrary to previous claims that memantine can improve cognition in AD patients, without serious side effects on normal learning and memory abilities, we found that rats treated only with memantine exhibited the impaired spatial learning and memory ability. We conclude that memantine can improve cognition related to an excitotoxicity-induced pathologic state, but the potential side effects of memantine on the physiological processes should be considered.