Military Medical Research最新文献

Background: Fibrosis constitutes a significant pathophysiological mechanism in the clinical progression of benign prostatic hyperplasia (BPH) and represents a contributing factor to the ineffectiveness of prevailing pharmacological treatments. Emerging evidence suggests a close association between microbial presence and the development of fibrosis. Nonetheless, the potential involvement of microbes within prostatic tissue in the pathogenesis of BPH and prostatic fibrosis, along with the underlying mechanisms, remains unexplored.

Methods: Utilizing immunohistochemistry and microbial sequencing, we analyzed the microbes of prostate tissues from BPH patients with different degrees of prostate fibrosis and found that Salmonella enterica (S. enterica) was enriched in the high degree of prostate fibrosis. We developed prostate cell and animal models infected with the lipopolysaccharide of S. enterica (S.e-LPS) to assess its impact on prostate fibrosis. To elucidate the underlying functional mechanisms, we employed molecular biology techniques, including RNA degradation assays, N⁶-methyladenosine (m⁶A) dot blotting, RNA immunoprecipitation, and m⁶A immunoprecipitation.

Results: Microbial diversity differed between low- and high-fibrosis groups, with S. enterica showing the highest mean abundance among the four species that differed significantly. S.e-LPS was detected in S. enterica-rich prostate tissue and was found to significantly promote cell proliferation, cell contractility, lipid peroxidation, and the induction of ferroptosis. Animal experiments demonstrated that S.e-LPS infection led to pronounced hyperplasia of the prostatic epithelium, with epithelial thickness increasing to 1.57 times that of the sham group, and collagen fibrosis increasing to 2.84 times that of the sham group, thereby exacerbating prostatic tissue fibrosis in rats. In vitro experiments further revealed that S.e-LPS promoted prostate cell fibrosis by inducing ferroptosis. Mechanistically, it was determined that S.e-LPS regulates ferroptosis via AlkB homolog 5 (ALKBH5)-mediated m⁶A modification, which affects the stability of glutathione peroxidase 4 (GPX4) mRNA, thereby affecting prostatic fibrosis.

Conclusion: The findings of this study suggest that S. enterica promotes prostatic fibrosis through ALKBH5-m⁶A-GPX4-mediated ferroptosis. This research offers novel insights for the development of new therapeutic targets and personalized strategies for the prevention and treatment of BPH from the perspectives of microbes and epigenetics.

Background: Second primary malignancies (SPMs) account for over 30% of total deaths in head and neck cancer (HNC) patients. The increasing use of radiotherapy raises concerns about the elevated risk of radiation-associated SPMs. This study aimed to investigate the age-stratified association between radiotherapy and SPM risk in survivors of non-metastatic primary HNC.

Methods: Using data from the Surveillance, Epidemiology, and End Results program (2004-2015), incidence rate ratios (IRRs) and standardized incidence ratios (SIRs) were evaluated for solid and hematologic SPMs associated with radiotherapy within different age groups. Follow-up for hematologic and solid SPMs began 2 and 5 years, respectively, after the diagnosis of first primary HNC. The IRRs for SPMs were compared between radiotherapy-exposed and unexposed groups using multivariable modified Poisson regression. The SIRs were computed as the ratio of observed cancers in the cohort to expected cases derived from sex-, age-, and calendar year-matched general population incidence rates.

Results: The study included 75,209 2-year survivors, with 73.2% being male and a median age of 60 years. Of these, 58,063 had survived 5 years or more. Radiotherapy was associated with an increased risk of solid SPMs [IRR = 1.16, 95% confidence interval (CI) 1.08-1.24; P < 0.001]. The associations varied significantly among young (aged 15-39 years), middle-aged (aged 40 - 64 years), and elderly (aged 65-89 years) patients. Specifically, radiotherapy was associated with an increased risk of solid SPMs in middle-aged patients (IRR = 1.21, 95% CI 1.11-1.32; P < 0.001), and a decreased risk of hematologic SPMs in elderly patients (IRR = 0.77, 95% CI 0.60-0.99; P = 0.045). Compared with the general population, young patients had an elevated risk of radiotherapy-associated second primary non-Hodgkin lymphoma (SIR = 4.01, 95% CI 1.47-8.74). Middle-aged patients showed the highest SIR for SPMs in the bones/joints (SIR = 7.72, 95% CI 4.32-12.73), while elderly patients had the highest SIR for second primary esophageal malignancies (SIR = 3.87, 95% CI 2.91-5.05). Males were more likely to develop solid SPMs compared to females.

Conclusions: This study reveals an age-stratified association between radiotherapy and the risk of SPMs in HNC patients. These findings highlight the importance of considering patient age when making treatment decisions for HNC and suggest that long-term surveillance is necessary for high-risk groups.

Brain diseases are characterized by high incidence, disability, and mortality rates. Their elusive nature poses a significant challenge for early diagnosis. Magnetic particle imaging (MPI) is a novel imaging technique with high sensitivity, high temporal resolution, and no ionizing radiation. It relies on the nonlinear magnetization response of superparamagnetic iron oxide nanoparticles (SPIONs), allowing visualization of the spatial concentration distribution of SPIONs in biological tissues. MPI is expected to become a mainstream technology for the early diagnosis of brain diseases, such as cancerous, cerebrovascular, neurodegenerative, and inflammatory diseases. This review provides an overview of the principles of MPI, explores its potential applications in brain diseases, and discusses the prospects for the diagnosis and management of these diseases.