Alveolar Echinococcosis (AE) is a zoonotic parasitic disease caused by Echinococcus multilocularis, but its pathogenesis remains unclear. The primary objective of this study is to explore whether Echinococcus multilocularis protoscoleces (PSCs) regulate macrophage polarization and glucose metabolism by PI3K/Akt/mTOR signaling pathway. We found that large numbers of CD68⁺ macrophages gathered in close liver issue from the lesion in AE patients. PSCs preferentially differentiated into M2 macrophages and the expressions of HK1, PFKL, PKM2, PI3K, Akt, p-Akt, mTOR and p-mTOR increased. The above results show that Echinococcus multilocularis protoscoleces enhance glycolysis to promote M2 macrophages through PI3K/Akt/mTOR signaling pathway.

Background: A number of studies have found that metabolic disorders are the characteristic manifestations of tumor cells. However, the effects of hypoxic environment on mitochondrial function and glucose metabolism of tumor cells were still unclear. The study wanted to explore the regulatory mechanism of hypoxic environment on mitochondrial function and metabolism in gastric cancer cells. Methods: The animal model of gastric cancer and MKN45 were treated in a hypoxic environment. Mitochondrial membrane potential and reactive oxygen species (ROS) levels were analyzed by flow cytometry, qPCR was used to detect the expression levels of glycose metabolism key enzymes, damage repair genes and mitochondrial DNA (mtDNA) copy numbers in gastric cancer. Results: Compared with 2,000 m normal gastric cancer tissue, the decreased of mitochondrial membrane potential and the production of ROS reduced, the expressions of glucose metabolism genes [the M1 isoform of Hexokinase (HK1), pyruvate kinase (PKM), Succinate dehydrogenase (SDHA), Glucose-6-phosphate dehydrogenase (G6PD)], homologous recombination repair gene (RAD51) and repair DNA double-stranded broken gene (ASTCT2) increased, and aerobic respiration reduced in gastric cancer cells. In the hypoxic environment, the decreased of mitochondrial membrane potential reduced, the production of ROS and mtDNA copies increased, HK1 expression increased, the expressions of SDHA, G6PD, RAD51 and ASCT-2 decreased, and the aerobic respiration decreased. Conclusions: Hypoxia plays an important role in maintaining mitochondrial functions in gastric cancer cells by promoting glycolysis and inhibiting mitochondrial aerobic respiration capacity.

Background: Alveolar echinococcosis (AE), caused by Echinococcus multilocularis, is a severe parasitic disease exhibiting tumor-like growth and profound immune evasion. The spatial organization and immunosuppressive mechanisms within the human AE lesion microenvironment remain poorly characterized. Methods: High-dimensional imaging mass cytometry (IMC) was performed on liver tissue sections from six patients with histologically confirmed AE, comparing lesion-proximal (close liver tissue, CLT) and lesion-distal (distant liver tissue, DLT) regions. This approach enabled simultaneous profiling of immune cell infiltration, spatial heterogeneity, immune checkpoint expression, and microenvironmental architecture. Complementary immunofluorescence and immunohistochemistry were used to evaluate age-related differences in neutrophil subsets between pediatric and adult patients. Results: Sixteen immune cell types were resolved by IMC, revealing distinct spatial distributions: CD15- neutrophils and CD4+ effector memory T (Tem) cells accumulated in partially necrotic zones; M1/M2 macrophages and dendritic cells formed ring-like structures around cytotoxic T lymphocyte (CTL)-rich areas; CD4+ and CD8+ effector T cells exhibited dispersed circular patterns. M2 macrophages showed a negative correlation with T cells—suggesting T cell exhaustion—and a positive association with CD15+ neutrophils but not CD15-neutrophils. Immune checkpoint molecules were generally expressed at low levels in CLT, with focal PD-1/PD-L1 co-expression, broad CD47 distribution, rare NKG2A ⁺ cells, and TIGIT enrichment in innate NK cells. Based on the TIMELASER classification system, the AE immune microenvironment was categorized into three subtypes: marrow-enriched immunosuppressive, stroma-enriched immunosuppressive, and immune-resident. Significantly higher densities of both CD15+ and CD15- neutrophils were observed in CLT of pediatric patients compared to adults. Conclusion: This study provides the first spatially resolved map of the immune landscape in human AE, revealing dynamic immunosuppressive niches shaped by myeloid–lymphoid crosstalk and checkpoint regulation. These findings offer new insights into early immune evasion mechanisms and potential targets for host-directed therapeutic strategies.

Alveolar echinococcosis (AE), a parasitic disease caused by the Echinococcus multilocularis (E. multilocularis), primarily affects the liver and has the potential to spread to other organs, which can be quite invasive. This disease has been receiving increasing attention on a global scale. The objective of this study is to evaluate the clinical value of droplet digital polymerase chain reaction (ddPCR) technology in the diagnosis of hepatic alveolar echinococcosis (HAE) through the detection of plasma and to explore the relationship between ddPCR quantitative results and lesion size and staging. Researchers collected blood samples from 57 confirmed HAE patients and 34 control samples from individuals without AE. Subsequently, ddPCR was utilized to detect E. multilocularis circulating free DNA (Em-cfDNA) in the plasma. Furthermore, next-generation sequencing (NGS) and antibody tests were utilized as comparative methods. The sensitivity of ddPCR was found to be 91.22%, with a 100% specificity, thereby demonstrating superiority over conventional serum antibody tests, which exhibited a sensitivity of 89.50% and a specificity of 85.3%. ddPCR demonstrated a comparable performance to NGS testing, which also demonstrated a sensitivity of 89.50% and a 100% specificity. ddPCR is characterized by its ease of operation and cost-effectiveness. It also holds significant value for screening in resource-limited areas, thereby helping to improve early diagnosis rates for HAE and enhance patient prognosis. Subsequent research endeavors will concentrate on the refinement of this technology and the validation of its applications in the domains of diagnosis, monitoring, and follow-up.

Objective: This study aims to investigate the regulatory mechanism by which the acidic microenvironment modulates LAMC2 expression in non-small cell lung cancer (NSCLC) and to elucidate its roles in tumor cell proliferation, migration, invasion, and associated signaling pathways, thereby providing a theoretical foundation for targeted lung cancer therapies. Methods: A cohort of 104 pathologically confirmed NSCLC patients treated at a designated hospital from January 2018 to December 2021 was enrolled. RNA-seq data from the TCGA database were analyzed to evaluate LAMC2 expression differences and prognostic implications using the GEPIA2 tool. In vitro assays assessed the acidic microenvironment’s impact on LAMC2 expression, with functional evaluations of LAMC2 overexpression and knockdown on cellular behaviors. Results: The LAMC2 mRNA levels were elevated across multiple tumor types and correlated with unfavorable prognoses in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). The acidic microenvironment significantly upregulated LAMC2 expression through HIF-1α-mediated transcriptional activation. LAMC2, in turn, promoted NSCLC cell proliferation, migration, and invasion by activating the PI3K/Akt signaling pathway and inducing epithelial–mesenchymal transition (EMT). Clinically, a high LAMC2 expression was associated with poor tumor differentiation, advanced TNM staging, and reduced 3-year survival rates. Moreover, LAMC2 positively correlated with immune checkpoint molecules (e.g., PD-L1, CTLA-4), implying its involvement in immune evasion. Conclusion: The acidic microenvironment upregulates LAMC2 via HIF-1α-mediated transcriptional regulation and lactate accumulation, thereby driving malignant progression in NSCLC. Elevated LAMC2 levels are linked to enhanced proliferation, migration, invasion, and dismal patient outcomes, underscoring its potential as a therapeutic target for precision oncology.