Yingying Zhang

Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant pathogen that poses a major public health concern. It predominantly infects immunocompromised individuals and is frequently associated with severe pulmonary complications, including acute lung injury. Diosmetin, a natural flavonoid, known for its anti-inflammatory, antioxidant, and anti-infective properties. Nevertheless, its therapeutic mechanism in the treatment of acute pneumonia induced by MRSA remains unclear. Methods: In this study, we employed network pharmacology and molecular docking to elucidate the mechanisms underlying the therapeutic effect of diosmetin against MRSA-induced pneumonia. An MRSA pneumonia model was established in Balb/c mice. The impacts of diosmetin on murine pneumonia were evaluated by detecting biochemical indicators via HE staining, ELISA, RT-qPCR, and WB. In vitro experiments utilized RAW264.7 macrophages to establish an MRSA infection model for further validation of the therapeutic mechanisms of diosmetin. Results: In vivo results demonstrated that diosmetin alleviated MRSA-induced lung injury and reduced mortality by inhibiting the release of pro-inflammatory cytokines. Furthermore, compared with model mice, diosmetin-treated mice showed reduced phosphorylation levels of NLRP3, pro-caspase-1, ASC, and NF-κB p65, along with an increased level of IκBα in lung tissue. In vitro experiments indicated that diosmetin effectively reduced the levels of pro-inflammatory cytokines in MRSA-infected RAW264.7 macrophages and exerted anti-inflammatory effects by modulating the expression of NLRP3, pro-caspase-1, ASC, IκBα, and NF-κB p65. Conclusions: Our results demonstrate that diosmetin alleviates MRSA-induced pneumonia in mice, and this protective effect is achieved through dual inhibition of the NF-κB/NLRP3 inflammasome axis.

Pseudomonas aeruginosa is an opportunistic pathogen that commonly causes infections in immunocompromised individuals with significant morbidity and mortality. Quercetin is a natural flavonoid abundantly present in fruits and vegetables, exerting potent anti-inflammatory effects in treatment of various diseases. However, the molecular mechanisms of quercetin in treatment of P. aeruginosa-induced acute lung inflammation are unclear. In this study, we exploited network pharmacology- and molecular docking-based approach to explore the potential mechanisms of quercetin against P. aeruginosa pneumonia, which was further validated via in vivo and in vitro experiments. The in vivo experiments demonstrated that quercetin alleviated the P. aeruginosa-induced lung injury by diminishing neutrophil infiltration and production of proinflammatory cytokines (IL-1β, IL-6, and TNF), which was associated with decreased mortality. Moreover, the quercetin-treated mice displayed decreased phosphorylation levels of PI3K, AKT, IκBα, and NF-κB p65 in lung tissues compared to non-drug-treated mice. Similarly, the in vitro study showed that the phosphorylation of these regulatory proteins and production of the proinflammatory cytokines were impaired in the quercetin-pretreated macrophages upon P. aeruginosa infection. Altogether, this study suggested that quercetin reduced the P. aeruginosa-induced acute lung inflammation by suppressing PI3K/AKT/NF-κB signaling pathway.

This study elucidated the chemical composition of essential oil from Centipeda minima (EOCM) and its antibacterial and antioxidant activities with two chemical monomers thymol and carvacrol. The main chemical composition of EOCM, analyzed by GC-MS, were trans-chrysanthenyl acetate, thymol, aromadendrene and β-caryophyllene. In the screening of antibacterial activity against S. aureus, two monomers with antibacterial activity were obtained: thymol and carvacrol. The MIC of EOCM, thymol and carvacrol were 0.625 mg/mL, 0.156 mg/mL and 0.156 mg/mL, respectively. The experimental results were shown that three drugs could inhibit the growth of S. aureus and inhibit the formation of biofilm by changing the permeability of cell membrane and interfering with the metabolic activities in bacteria. The scavenging effects of the three drugs on DPPH radical and hydroxyl radical showed that the antioxidant effect of the three drugs was EOCM > carvacrol > thymol.

The purpose of this study is to optimize the extraction process and study antioxidant activity of Polysaccharide extracted from Centipeda minima. The Box‐Behnken design‐response surface methodology was adopted to optimize the extraction process of polysaccharides from Centipeda minima. We purified the crude polysaccharides from Centipeda minima, as well as determined the purity, monosaccharide composition, and molecular weight of the purified fraction. Fourier transform infrared spectrometer (FT‐IR) and scanning electron microscopy (SEM) were used to analyze the structural features of the polysaccharides. Further, we investigated the antioxidant activities of different fractions of polysaccharides. Consequently, the results showed that the optimum extraction conditions for polysaccharides were: a liquid‐solid ratio of 26 mL/g, extraction temperature of 85.5 °C, and extraction time of 2.4 h. Moreover, the yield of polysaccharides measured under these conditions was close to the predicted value. After purification, we obtained four components of Centipeda minima polysaccharides (CMP). The purity, monosaccharide composition, molecular weight, and structural characteristics of CMP were different, but with similar infrared absorption spectra. CMP exhibited a typical infrared absorption characteristic of a polysaccharide. Besides, CMP displayed good antioxidant activity, with potential to scavenge DPPH radical, hydroxyl radical, and superoxide radical. Therefore, this study provides a reference for future research on the structure and biological activity of CMP, and lays a theoretical foundation for food processing and medicinal development of CMP.

The present study elucidated the structural characteristics and anti-inflammatory activity of a novel polysaccharide isolated from Orostachys fimbriata, which is a traditional Chinese medicinal plant. O. fimbriata polysaccharide (OFP) was extracted and subsequently purified by chromatography using a DEAE cellulose-52 and Sephadex G-75 column. The molecular weight was determined as 6.2 kDa. HPGPC and monosaccharide composition analysis revealed a homogeneous polysaccharide containing only Glc. Chromatography and spectral analysis showed that the possible chemical structure consisted of →4)-α-Glcp-(1→ and a small quantity of →4,6)-β-Glcp-(1→ in the main chain and →6)-β-Glcp-(1→, α-Glcp-(1→, and β-Glcp-(1→ in the side chain. Morphological analysis using scanning electron microscopy (SEM) and atomic force microscopy (AFM) indicated that OFP had a multi-branched structure, and the sugar chain molecules of polysaccharide appeared aggregated. OFP was found to exhibit anti-inflammatory activity by reducing the secretion of inflammatory factors in RAW264.7 cells and by decreasing the extent of xylene-induced ear swelling in mice.

Rationale: Acute lymphoblastic leukemia (ALL) has acute and severe onset characterized by fever, moderate to severe anemia, bone and joint pain, and sternal tenderness. It is easy to be misdiagnosed as rheumatic disease when joint pain is the first symptom. Patient concerns: A male Han, 18 years of age was admitted on July 15th, 2016 for multi-joint swelling and pain with intermittent fever for half a year which had aggravated in the last 10 days. Diagnosis: Based on symptoms, imaging, family history, and blood tests, he was first diagnosed with ankylosing spondylitis, but he was refractory to treatment. Bone marrow biopsy then revealed acute B-lymphoblastic leukemia (possibility Pro-B-ALL). Interventions: The patient was transferred to the hematology department on July 23rd, 2016 for chemotherapy. Outcomes: No joint pain occurred during follow-up, which ended on November 4th, 2018. Lessons: ALL may present with symptoms suggestive of rheumatic diseases like ankylosing spondylitis. Physicians should be aware of this possibility, especially in young patients.

Influenza A viruses (IAV) carrying reporter genes provide a powerful tool to study viral infection and pathogenesis in vivo, however, incorporating a non-essential gene into the IAV genome often results in virus attenuation and genetic instability. Very few studies have systematically compared different reporter IAVs, and most optimization attempts seem to lack authentic directions. In this study, we evaluated the ratio of genome copies to the number of infectious unit of two reporter IAVs, PR8-NS1-Gluc and PR8-PB2-Gluc. As a result, PR8-NS1-Gluc and PR8-PB2-Gluc produced 41.4 and 3.8 genomes containing noninfectious particles respectively for every such particle produced by parental PR8 virus. RdRp assay demonstrated that modification of segment NS by inserting reporter genes can interfere with the replication competitive property of the corresponding vRNAs, and the balance of the 8 segments of the reporter IAVs were drastically impaired in infected cells. As a consequence, large amounts of NS-null noninfectious particles were produced during the PR8-NS1-Gluc packaging. In summary, we unravel a mechanism underlying attenuation of reporter IAVs, which suggests a new approach to restore infectivity and virulence by introducing extra mutations compensating for the impaired replication property of corresponding segments.

Influenza A virus (IAV) causes seasonal epidemics and occasional but devastating pandemics, which are major public health concerns. Because the effectiveness of seasonal vaccines is highly variable and the currently available drugs are limited in their efficacy because of the emergence of drug resistance, there is an urgent need to develop novel antivirals. In this study, we characterized a recombinant IAV-carrying Gaussia luciferase (Gluc) gene and determined its potential as a tool for evaluating therapeutics. We demonstrated that this recombinant IAV is replication-competent in tissue culture and pathogenic in mice, although it is slightly attenuated compared to the parental virus. Luciferase expression correlated well with virus propagation both in vitro and in vivo, providing a simple measure for viral replication in tissue culture and in mouse lungs. To demonstrate the utility of this virus, ribavirin and oseltamivir phosphate were used to treat the IAV-infected cells and mice, and we observed the dose-dependent inhibition of viral replication by a luciferase assay. Moreover, the decreased luciferase expression in the infected lungs could predict the protective efficacy of antiviral interventions as early as day 2 post virus challenge. In summary, this study provides a new and quantitative approach to evaluate antivirals against IAV.