Activation of the RIG-I/MAVS Signaling Pathway during Human Adenovirus Type 3 Infection Impairs the Pro-Inflammatory Response Induced by Secondary Infection with Staphylococcus aureus.

The exacerbation of pneumonia in children with human adenovirus type 3 (HAdV-3E) is secondary to a Staphylococcus aureus (S. aureus) infection. The influence of host-pathogen interactions on disease progression remains unclear. It is important to note that S. aureus infections following an HAdV-3E infection are frequently observed in clinical settings, yet the underlying susceptibility mechanisms are not fully understood. This study utilized an A549 cell model to investigate secondary infection with S. aureus following an HAdV-3E infection. The findings suggest that HAdV-3E exacerbates the S. aureus infection by intensifying lung epithelial cell damage. The results highlight the role of HAdV-3E in enhancing the interferon signaling pathway through RIG-I (DDX58), resulting in the increased expression of interferon-stimulating factors like MX1, RSAD2, and USP18. The increase in interferon-stimulating factors inhibits the NF-κB and MAPK/P38 pro-inflammatory signaling pathways. These findings reveal new mechanisms of action for HAdV-3E and S. aureus in secondary infections, enhancing our comprehension of pathogenesis.

Early ambulation protocol after diagnostic transfemoral cerebral angiography: an evidence-based practice project.

BACKGROUND: No uniform consensus has been achieved regarding the ambulation protocol after transfemoral cerebral angiography (TFA). Until now, in most hospitals patients are prescribed 8-12 h strict immobilization along with bed rest in the supine position after TFA in China, which causes great discomfort to patients. OBJECTIVE: To evaluate the effect of an evidence-based early ambulation protocol on the prevention of vascular complications and general discomfort in patients following transfemoral cerebral angiography (TFA). METHODS: A prospective quasi-experimental study was conducted on 214 patients undergoing TFA with manual compression. Patients in the experimental group were placed supine position for 2 h with a sandbag placed on the wound dressing, followed by a semi-seated position for another 2 h. After this period, patients took 2 h bed rest (move freely) with the sandbag removed, and were allowed to get out of bed 6 h after TFA. Patients in the control group were restricted to an 8 h bed rest in a supine position with the affected leg straight and immobilized. The vascular complications (bleeding, hematoma, ecchymosis) and levels of comfort (low back pain, leg pain, and blood pressure) were evaluated after the procedure. Numeric Rating Scale (NRS) pain scores, systolic blood pressure (SBP); diastolic blood pressure (DBP) were measured hourly for 8 h after TFA. RESULTS: There was no significant difference in the two groups with regard to vascular complications including bleeding events (P = 0.621), bleeding volume (P = 0.321), and area of hematoma (P = 0.156). The area of ecchymosis in the experimental group was significantly smaller than the control group (P = 0.031). Compared with the control group, the NRS score for low back pain in the 4th, 5th, 6th, 7th, and 8th hour after TFA were significantly lower (P < 0.05), and the NRS score for leg pain in the 5th, 6th, 7th, 8th hour after TFA were significantly lower (P < 0.05). The SBP and DBP in the 6th, 7th, and 8th hour after TFA were significantly lower than the control group (all P < 0.05). CONCLUSIONS: The evidence-based early ambulation protocol can effectively and safely increase comfort and decrease the pain level for patients undergoing TFA, without change in the incidence of vascular complications.

ZnO-Doped Metal-Organic Frameworks Nanoparticles: Antibacterial Activity and Mechanisms.

Metal-Organic Frameworks (MOFs) offer new ideas for the design of antibacterial materials because of their antibacterial properties, high porosity and specific surface area, low toxicity and good biocompatibility compared with other nanomaterials. Herein, a novel antimicrobial nanomaterial, MIL-101(Fe)@ZnO, has been synthesized by hydrothermal synthesis and characterized by FTIR, UV-vis, ICP-OES, XRD, SEM, EDS and BET to show that the zinc ions are doped into the crystal lattice of MIL-101(Fe) to form a Fe-Zn bimetallic structure. MIL-101(Fe)@ZnO was found to be effective against a wide range of antibacterial materials including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Acinetobacter junii and Staphylococcus epidermidis. It has a significant antibacterial effect, weak cytotoxicity, high safety performance and good biocompatibility. Meanwhile, MIL-101(Fe)@ZnO was able to achieve antibacterial effects by causing cells to produce ROS, disrupting the cell membrane structure, and causing protein leakage and lipid preoxidation mechanisms. In conclusion, MIL-101(Fe)@ZnO is an easy-to-prepare antimicrobial nanomaterial with broad-spectrum bactericidal activity and low toxicity.

Ecological model of health behaviour of hypertensive stroke patients at the end of recovery period.

AIMS AND OBJECTIVES: This study aimed to construct a structural equation model guided by the ecological model to explore the factors influencing health behaviour among hypertensive stroke patients 6 months post-stroke. BACKGROUND: Health behaviour is important for recurrence prevention in hypertensive stroke patients. Moreover, previous studies have indicated that health behaviour at the end of the recovery period is of particular concern. The ecological model provides an integrated perspective for explaining the factors influencing health behaviour. DESIGN: A cross-sectional study guided by the STROBE. METHODS: A total of 121 hypertensive stroke patients were included to assess stroke knowledge, health belief, depression, family function, chronic illness resource and health behaviour. A structural equation model was used to explore the health behaviour's factors and pathways. RESULTS: In the final ecological model, sex, education level, depression and chronic illness resource directly affected health behaviour. Stroke knowledge directly affected health behaviour and indirectly affected health behaviour through health belief and chronic illness resource. Family function indirectly affected health behaviour through health belief, depression and chronic illness resource. Health belief affected health behaviour indirectly through depression and chronic illness resource. CONCLUSIONS: Hypertensive stroke patients' health behaviour is jointly and interactively influenced by stroke knowledge, health belief, depression, family function and chronic illness resource. In particular, chronic illness resource is an important mediator of health behaviour. RELEVANCE TO CLINICAL PRACTICE: For clinical practitioners, health behaviour of men and patients with low educational levels should be specifically focused on. Additionally, it is necessary to provide stroke knowledge, establish health beliefs, control depression emotion and improve family function. Furthermore, chronic illness resources should be improved particularly due to its important mediating role. PATIENT OR PUBLIC CONTRIBUTION: Participants completed demographic and disease-related questionnaires during hospitalisation and completed other questionnaires when returning to hospital at 6 months follow-up.

MIL-101 (Fe) @Ag Rapid Synergistic Antimicrobial and Biosafety Evaluation of Nanomaterials.

Metal-organic frameworks (MOFs), which have become popular in recent years as excellent carriers of drugs and biomimetic materials, have provided new research ideas for fighting pathogenic bacterial infections. Although various antimicrobial metal ions can be added to MOFs with physical methods, such as impregnation, to inhibit bacterial multiplication, this is inefficient and has many problems, such as an uneven distribution of antimicrobial ions in the MOF and the need for the simultaneous addition of large doses of metal ions. Here, we report on the use of MIL-101(Fe)@Ag with efficient metal-ion release and strong antimicrobial efficiency for co-sterilization. Fe-based MIL-101(Fe) was synthesized, and then Ag+ was uniformly introduced into the MOF by the substitution of Ag+ for Fe3+. Scanning electron microscopy, powder X-ray diffraction (PXRD) Fourier transform infrared spectroscopy, and thermogravimetric analysis were used to investigate the synthesized MIL-101(Fe)@Ag. The characteristic peaks of MIL-101(Fe) and silver ions could be clearly seen in the PXRD pattern. Comparing the diffraction peaks of the simulated PXRD patterns clearly showed that MIL-101(Fe) was successfully constructed and silver ions were successfully loaded into MIL-101(Fe) to synthesize an MOF with a bimetallic structure, that is, the target product MIL-101(Fe)@Ag. The antibacterial mechanism of the MOF material was also investigated. MIL-101(Fe)@Ag exhibited low cytotoxicity, so it has potential applications in the biological field. Overall, MIL-101(Fe)@Ag is an easily fabricated structurally engineered nanocomposite with broad-spectrum bactericidal activity.

Anti-Influenza Virus Study of Composite Material with MIL-101(Fe)-Adsorbed Favipiravir.

Nanomaterial technology has attracted much attention because of its antibacterial and drug delivery properties, among other applications. Metal-organic frameworks (MOFs) have advantages, such as their pore structure, large specific surface area, open metal sites, and chemical stability, over other nanomaterials, enabling better drug encapsulation and adsorption. In two examples, we used the common pathogenic bacterium Staphylococcus aureus and highly infectious influenza A virus. A novel complex MIL-101(Fe)-T705 was formed by synthesizing MOF material MIL-101(Fe) with the drug favipiravir (T-705), and a hot solvent synthesis method was applied to investigate the in vitro antibacterial and antiviral activities. The results showed that MIL-101(Fe)-T705 combined the advantages of nanomaterials and drugs and could inhibit the growth of Staphylococcus aureus at a concentration of 0.0032 g/mL. Regarding the inhibition of influenza A virus, MIL-101(Fe)-T705 showed good biosafety at 12, 24, 48, and 72 h in addition to a good antiviral effect at concentrations of 0.1, 0.2, 0.4, 0.8, 1.6, and 3 µg/mL, which were higher than MIL-101(Fe) and T-705.

Silencing of histone deacetylase 2 suppresses malignancy for proliferation, migration, and invasion of glioblastoma cells and enhances temozolomide sensitivity.

Histone deacetylases (HDACs) can regulate the progression of various cancers, while their roles in glioblastoma multiforme (GBM) are not well known. Our present study investigated the expression of class I HDACs (HDAC1, 2, 3, 8) in GBM U87, A172, U251, and LN229 cells and compared their levels with that in primary normal human astrocytes (NHA) cells. It showed that HDAC2 expression is significantly up-regulated in GBM cells. Silencing of HDAC2 via its specific siRNAs can suppress the in vitro proliferation, migration, and invasion of GBM U87 and A172 cells. Furthermore, silencing of HDAC2 can increase the sensitivity of GBM cells to temozolomide (TMZ), a standard-of-care during clinical GBM treatment. This might be due to that si-HDAC can significantly down-regulate the mRNA and protein expression of MRP1, while has no effect on ABCB1 and ABCG2. Schisandrin B (Sch B), a specific inhibitor of MRP1, can further increase the TMZ sensitivity in HDAC2-knocked down GBM cells. Collectively, our data revealed that targeted HDAC2 can suppress the malignancy of GBM cells and increase their sensitivity of TMZ via down-regulation of MRP1. It suggested that HDAC2 might be a potential target for GBM therapy and improvement in TMZ therapy efficiency.

Hypoxia-inducible factor-1α upregulation in microglia following hypoxia protects against ischemia-induced cerebral infarction.

Activated microglia were considered to be the toxic inflammatory mediators that induce neuron degeneration after brain ischemia. Hypoxia can enhance the expression of hypoxia-inducible factor-1α (HIF-1α) in microglia and cause microglial activation. However, intermittent hypoxia has been reported recently to be capable of protecting the body from myocardial ischemia. We established a high-altitude environment as the hypoxic condition in this study. The hypoxic condition displayed a neuroprotective effect after brain ischemia, and mice exposed to this condition presented better neurological performance and smaller infarct size. At the same time, a high level of HIF-1α, low level of isoform of nitric oxide synthase, and a reduction in microglial activation were also seen in ischemic focus of hypoxic mice. However, this neuroprotective effect could be blocked by 2-methoxyestradiol, the HIF-1α inhibitor. Our finding suggested that HIF-1α expression was involved in microglial activation in vitro and was regulated by oxygen supply. The microglia were inactivated by re-exposure to hypoxia, which might be due to overexpression of HIF-1α. These results indicated that hypoxic conditions can be exploited to achieve maximum neuroprotection after brain ischemia. This mechanism possibly lies in microglial inactivation through regulation of the expression of HIF-1α.