Protein-assisted synthesis of chitosan-coated minicells enhance dendritic cell recruitment for therapeutic immunomodulation within pulmonary tumors.

The efficacy of cancer therapies is significantly compromised by the immunosuppressive tumor milieu. Herein, we introduce a previously unidentified therapeutic strategy that harnesses the synergistic potential of chitosan-coated bacterial vesicles and a targeted chemotherapeutic agent to activate dendritic cells, thereby reshaping the immunosuppressive milieu for enhanced cancer therapy. Our study focuses on the protein-mediated modification of bacterium-derived minicells with chitosan molecules, facilitating the precise delivery of Doxorubicin to tumor sites guided by folate-mediated homing cues. These engineered minicells demonstrate remarkable specificity in targeting lung carcinomas, triggering immunogenic cell death and releasing tumor antigens and damage-associated molecular patterns, including calreticulin and high mobility group box 1. Additionally, the chitosan coating, coupled with bacterial DNA from the minicells, initiates the generation of reactive oxygen species and mitochondrial DNA release. These orchestrated events culminate in dendritic cell maturation via activation of the stimulator of interferon genes signaling pathway, resulting in the recruitment of CD4+ and CD8+ cytotoxic T cells and the secretion of interferon-ß, interferon-γ, and interleukin-12. Consequently, this integrated approach disrupts the immunosuppressive tumor microenvironment, impeding tumor progression. By leveraging bacterial vesicles as potent dendritic cell activators, our strategy presents a promising paradigm for synergistic cancer treatment, seamlessly integrating chemotherapy and immunotherapy.

Genetically engineered bacterium: Principles, practices, and prospects.

Advances in synthetic biology and the clinical application of bacteriotherapy enable the use of genetically engineered bacteria (GEB) to combat various diseases. GEB act as a small 'machine factory' in the intestine or other tissues to continuously produce heterologous proteins or molecular compounds and, thus, diagnose or cure disease or work as an adjuvant reagent for disease treatment by regulating the immune system. Although the achievements of GEBs in the treatment or adjuvant therapy of diseases are promising, the practical implementation of this new therapeutic modality remains a grand challenge, especially at the initial stage. In this review, we introduce the development of GEBs and their advantages in disease management, summarize the latest research advances in microbial genetic techniques, and discuss their administration routes, performance indicators and the limitations of GEBs used as platforms for disease management. We also present several examples of GEB applications in the treatment of cancers and metabolic diseases and further highlight their great potential for clinical application in the near future.

Comparison of autofluorescence and white-light bronchoscopies performed with the Evis Lucera Spectrum for the detection of bronchial cancers: a meta-analysis.

BACKGROUND: Many recent studies have reported that autofluorescence bronchoscopy (AFB) has a superior sensitivity and decreased specificity in the diagnosis of bronchial cancers when compared with white-light bronchoscopy (WLB). We specifically analyzed the diagnostic performances of autofluorescence imaging video bronchoscopy (AFI) performed with the Evis Lucera Spectrum from Olympus, which is a relatively novel approach in detecting and delineating bronchial cancers, and compared it to the older WLB method. METHODS: We searched the PubMed, Embase, Web of Science, and CNKI databases from inception to July 12th, 2018 for trials in which patients were diagnosed with lung cancer via concurrent or combined use of AFI and WLB. The included studies were required to have a histologic diagnosis as the gold standard comparison, and a sufficient amount of data was extracted to assess the diagnostic capacity. A 2×2 table was constructed, and the area under the receiver-operating characteristic curve (AUC) of AFI and WLB was estimated by using a stochastic model for diagnostic meta-analysis using STATA software. RESULTS: A total of 10 articles were eligible for the meta analysis, comprising 1,830 patients with complete data included in the analysis. AFI showed a superior sensitivity of 0.92 (95% CI, 0.88-0.95) over WLB's 0.70 (95% CI, 0.58-0.80) with P<0.01, and a comparable specificity of 0.67 (95% CI, 0.51-0.80) compared with WLB's 0.78 (95% CI, 0.68-0.86) with P=0.056. Egger's test P value (0.225) demonstrated that there was no publication bias. CONCLUSIONS: Our research showed that in the evaluation of bronchial cancers, AFI was superior to conventional WLB. With its higher sensitivity, AFI could be valuable for avoiding misdiagnosis.

Ganoderic acid A attenuates lipopolysaccharide-induced lung injury in mice.

The present study aimed to investigate the protective effects of ganoderic acid A (GAA) on lipopolysaccharide (LPS)-induced acute lung injury. In mouse model of LPS-induced acute lung injury, we found that GAA led to significantly lower lung wet-to-dry weight ratio and lung myeloperoxidase activity, and attenuated pathological damages. In addition, GAA increased superoxide dismutase activity, but decreased malondialdehyde content and proinflammatory cytokines levels in the bronchoalveolar lavage fluid. Mechanistically, GAA reduced the activation of Rho/ROCK/NF-κB pathway to inhibit LPS-induced inflammation. In conclusion, our study suggests that GAA attenuates acute lung injury in mouse model via the inhibition of Rho/ROCK/NF-κB pathway.