Biomedical and environmental sciences : BES最新文献

Objective: Genotypes (G) 1, 3, and 5 of the Japanese encephalitis virus (JEV) have been isolated in China, but the dominant genotype circulating in Chinese coastal areas remains unknown. We searched for G5 JEV-infected cases and attempted to elucidate which JEV genotype was most closely related to human Japanese encephalitis (JE) in the coastal provinces of China.

Methods: In this study, we collected serum specimens from patients with JE in three coastal provinces of China (Guangdong, Zhejiang, and Shandong) from 2018 to 2020 and conducted JEV cross-neutralization tests against G1, G3, and G5.

Results: Acute serum specimens from clinically reported JE cases were obtained for laboratory confirmation from hospitals in Shandong (92 patients), Zhejiang (192 patients), and Guangdong (77 patients), China, from 2018 to 2020. Seventy of the 361 serum specimens were laboratory-confirmed to be infected with JEV. Two cases were confirmed to be infected with G1 JEV, 32 with G3 JEV, and two with G5 JEV.

Conclusion: G3 was the primary infection genotype among JE cases with a definite infection genotype, and the infection caused by G5 JEV was confirmed serologically in China.

Objective: Intracranial hemorrhage (ICH), the second most common subtype of stroke, exacerbates the disruption of the blood-brain barrier (BBB), leading to vasogenic edema, plasma protein extravasation, and infiltration of neurotoxic substances. The clearance capacity of the brain plays a crucial role in maintaining BBB homeostasis and facilitating patient recovery after hemorrhage. This study aimed to investigate the effect of circadian rhythms on BBB function, neuronal damage, and clearance capabilities.

Methods: The transwell model and hemoglobin were co-cultured to simulate the BBB environment after ICH. After intervention with different light groups, neuronal apoptosis was determined, glial phagocytosis was analyzed, the expression of endogenous clearing-related proteins aquaporin 4 (AQP4) and low-density lipoprotein receptor-related protein 1 (LRP1) was detected by western blotting and immunofluorescence dual standard method, and the expression of the tight junction protein occludin and melatonin receptor 1A (MTNR1A) was quantitatively analyzed.

Results: Circadian rhythms play a key role in maintaining the integrity of the BBB, reducing oxidative stress-induced neuronal damage, and improving microglial phagocytosis. Meanwhile, the expression of occludin and MTNR1A in neurovascular unit (NVU) co-cultured with hemoglobin improved the expression of AQP4 and LRP1, the key proteins in the NVU's endogenous brain clearance system.

Conclusion: Circadian rhythm (alternating black and white light) protects the NVU BBB function after ICH, promotes the expression of proteins related to the clearance of the hematoma, provides new evidence for the clinical treatment of patients recovering from ICH, and improves the circadian rhythm to promote brain metabolism and hematoma clearance.

Lung cancer is the top cause of cancer deaths globally. Advances in immune checkpoint inhibitors (ICIs) have transformed cancer treatment, but their use in lung cancer has led to more side effects. This study examined if past pulmonary tuberculosis (TB) affects ICIs' effectiveness and safety in lung cancer treatment. We reviewed lung cancer patients treated with ICIs at Beijing Chest Hospital from January 2019 to August 2022. We compared outcomes and side effects between patients with and without prior TB. Of 116 patients (40 with TB history, 76 without), prior TB didn't reduce treatment effectiveness but did increase severe side effects. Notably, older patients (≥ 65 years) faced a higher risk of severe side effects. Detailed cases of two patients with severe side effects underscored TB as a risk factor in lung cancer patients receiving ICIs, stressing the need for careful monitoring and personalized care.

Melanocytes derived from neural crest cells harbor the BRAF ^V600E mutation, which is the predominant driver of nevus formation in humans. This mutation leads to malignant cell proliferation and subsequent cell cycle arrest, culminating in oncogene-induced senescence and nevus development. Nevertheless, emerging evidence has highlighted the heterogeneity of cellular senescence markers in BRAF ^V600E-induced senescent melanocytes. Moreover, the capacity of melanocytes within nevi to regain their proliferative ability raises questions about the molecular mechanisms by which BRAF ^V600E, via the mitogen-activated protein kinase signaling pathway, triggers nevus formation. This study provides an overview and discussion of the molecular mechanisms underpinning BRAF ^V600E-induced melanocyte nevus formation and the relevant animal models employed for their elucidation. It also highlights the significance of elucidating dynamic changes in cytoplasmic and nuclear substrates that interact with phosphorylated extracellular signal-regulated protein kinases 1 and 2 and underscores the value of using targeted BRAF ^V600E animal models created through gene editing technologies.

Objective: Triple-negative breast cancer (TNBC) poses a significant challenge for treatment efficacy. CD8+ T cells, which are pivotal immune cells, can be effectively analyzed for differential gene expression across diverse cell populations owing to rapid advancements in sequencing technology. By leveraging these genes, our objective was to develop a prognostic model that accurately predicts the prognosis of patients with TNBC and their responsiveness to immunotherapy.

Methods: Sample information and clinical data of TNBC were sourced from The Cancer Genome Atlas and METABRIC databases. In the initial stage, we identified 67 differentially expressed genes associated with immune response in CD8+ T cells. Subsequently, we narrowed our focus to three key genes, namely CXCL13, GBP2, and GZMB, which were used to construct a prognostic model. The accuracy of the model was assessed using the validation set data and receiver operating characteristic (ROC) curves. Furthermore, we employed various methods, including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, immune infiltration, and correlation analyses with CD274 (PD-L1) to explore the model's predictive efficacy in immunotherapeutic responses. Additionally, we investigated the potential underlying biological pathways that contribute to divergent treatment responses.

Results: We successfully developed a model capable of predicting the prognosis of patients with TNBC. The areas under the curve (AUC) values for the 1-, 3-, and 5-year survival predictions were 0.618, 0.652, and 0.826, respectively. Employing this risk model, we stratified the samples into high- and low-risk groups. Through KEGG enrichment analysis, we observed that the high-risk group predominantly exhibited enrichment in metabolism-related pathways such as drug and chlorophyll metabolism, whereas the low-risk group demonstrated significant enrichment in cytokine pathways. Furthermore, immune landscape analysis revealed noteworthy variations between (PD-L1) expression and risk scores, indicating that our model effectively predicted the response of patients to immune-based treatments.

Conclusion: Our study demonstrates the potential of CXCL13, GBP2, and GZMB as prognostic indicators of clinical outcomes and immunotherapy responses in patients with TNBC. These findings provide valuable insights and novel avenues for developing immunotherapeutic approaches targeting TNBC.

Objective: Pertussis cases have increased markedly since 2018 in Guangxi. The aim of this study was to evaluate antibody levels and the infection status of pertussis in the resident population.

Method: A total of 10,215 serum samples from residents were collected from August-November 2018 and tested for anti-pertussis IgG and toxin IgG using the enzyme-linked immunosorbent assay (ELISA).

Results: Of the collected samples, 1,833 (17.94%) tested positive for anti-pertussis IgG, with the median concentration of 16.06 IU/mL. Antibody level < 10 IU/mL accounted for more than 60% in children under 4 years of age, but declined with age, whereas the percentages of the other three levels (10-40, 40-50, and ≥ 50 IU/mL) increased almost with age ( P < 0.001). Moreover, 7,924 samples were selected for anti-pertussis toxin IgG, of which 653 (8.24%) tested positive (≥ 40 IU/mL) with the median concentration of 5.89 IU/mL, and 204 participants (2.56%) had recent pertussis infection (≥ 100 IU/mL). Among the different age groups, the highest rates of positivity and recent infection were observed at 11-20 years of age, the lowest positivity rate at 5 years of age, and the lowest recent infection rate at 4 years of age ( P < 0.001, P = 0.005, respectively).

Conclusion: The survey results showed that all age groups in Guangxi lacked immunity against pertussis, which was one of the main factors contributing to the resurgence of pertussis in 2018. In addition, the prevalence of pertussis is relatively high in Guangxi, and its incidence is seriously underestimated, especially in adolescents and adults.

Objective: Recent studies have indicated potential anti-inflammatory effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on asthma, which is often comorbid with type 2 diabetes mellitus (T2DM) and obesity. Therefore, we conducted a meta-analysis to assess the association between the administration of glucagon-like peptide-1 (GLP-1) receptor-based agonists and the incidence of asthma in patients with T2DM and/or obesity.

Methods: PubMed, Web of Science, Embase, the Cochrane Central Register of Controlled Trials, and Clinicaltrial.gov were systematically searched from inception to July 2023. Randomized controlled trials (RCTs) of GLP-1 receptor-based agonists (GLP-1RA, GLP-1 based dual and triple receptor agonist) with reports of asthma events were included. Outcomes were computed as risk ratios ( RR) using a fixed-effects model.

Results: Overall, 39 RCTs with a total of 85,755 participants were included. Compared to non-GLP-1 receptor-based agonist users, a trend of reduced risk of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments, although the difference was not statistically significant [ RR = 0.91, 95% confidence interval ( CI): 0.68 to 1.24]. Further Subgroup analyses indicated that the use of light-molecular-weight GLP-1RAs might be associated with a reduced the risk of asthma when compared with non-users ( RR = 0.65, 95% CI: 0.43 to 0.99, P = 0.043). We also performed sensitivity analyses for participant characteristics, study design, drug structure, duration of action, and drug subtypes. However, no significant associations were observed.

Conclusion: Compared with non-users, a modest reduction in the incidence of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments. Further investigations are warranted to assess the association between GLP-1 receptor-based agonists and the risk of asthma.

Objective: Genomic alterations and potential neoantigens for cervical cancer immunotherapy were identified in a cohort of Chinese patients with cervical squamous cell carcinoma (CSCC).

Methods: Whole-exome sequencing was used to identify genomic alterations and potential neoantigens for CSCC immunotherapy. RNA Sequencing was performed to analyze neoantigen expression.

Results: Systematic bioinformatics analysis showed that C>T/G>A transitions/transversions were dominant in CSCCs. Missense mutations were the most frequent types of somatic mutation in the coding sequence regions. Mutational signature analysis detected signature 2, signature 6, and signature 7 in CSCC samples. PIK3CA, FBXW7, and BICRA were identified as potential driver genes, with BICRA as a newly reported gene. Genomic variation profiling identified 4,960 potential neoantigens, of which 114 were listed in two neoantigen-related databases.

Conclusion: The present findings contribute to our understanding of the genomic characteristics of CSCC and provide a foundation for the development of new biotechnology methods for individualized immunotherapy in CSCC.