Single-cell transcriptome analysis of macrophage subpopulations contributing to chemotherapy resistance in ovarian cancer.

BACKGROUND: Ovarian cancer, a fatal gynecological malignancy, is primarily managed through surgery and chemotherapy. However, a significant challenge arises as patients frequently experience relapse due to chemotherapy resistance. This study delves into the complex functions and underlying mechanisms of macrophages in chemotherapy resistance in ovarian cancer. METHOD: The single-cell transcriptome sequencing data of ovarian cancer with or without chemotherapy were analyzed. Then, corresponding cell types were identified, and macrophages were extracted from all cells. Following the standardized single-cell analysis using the Seurat package, 15 distinct macrophage clusters were found and differentially expressed genes among them were analyzed. Moreover, their association with chemotherapy resistance was explored through cell proportions and gene expression. RESULT: In the single-cell transcriptomic analysis of ovarian cancer tissues before and after chemotherapy, the cellular proportion of CXCL5+ macrophages, THBS1+ macrophages, and MMP9+ macrophages were significantly increased following chemotherapy. Further investigation revealed that these macrophage subpopulations upregulated the expression of multiple pro-tumorigenic angiogenic or invasive factors, in addition to CXCL5, THBS1, and MMP9, including CTSL, CXCL1, and CCL18. Finally, pathway enrichment analysis revealed the significant activation of signaling pathways, such as NOD-like receptor, MAPK, and TNF in these macrophage subpopulations, which provides direction for studying the mechanism of these subpopulations. CONCLUSION: CXCL5+, THBS1+, and MMP9+ macrophage subpopulations exhibit an increased cellular prevalence post-chemotherapy and pro-tumorigenic molecular expression profiles, suggesting a close association with chemoresistance in ovarian cancer. These findings contribute to our understanding of the roles and mechanisms of macrophages in ovarian cancer chemoresistance, providing a theoretical basis and direction for the development of therapies targeting macrophages in overcoming ovarian cancer chemoresistance.

Reinforcing the immunogenic cell death to enhance cancer immunotherapy efficacy.

Immunogenic cell death (ICD) has been a revolutionary modality in cancer treatment since it kills primary tumors and prevents recurrent malignancy simultaneously. ICD represents a particular form of cancer cell death accompanied by production of damage-associated molecular patterns (DAMPs) that can be recognized by pattern recognition receptors (PRRs), which enhances infiltration of effector T cells and potentiates antitumor immune responses. Various treatment methods can elicit ICD involving chemo- and radio-therapy, phototherapy and nanotechnology to efficiently convert dead cancer cells into vaccines and trigger the antigen-specific immune responses. Nevertheless, the efficacy of ICD-induced therapies is restrained due to low accumulation in the tumor sites and damage of normal tissues. Thus, researchers have been devoted to overcoming these problems with novel materials and strategies. In this review, current knowledge on different ICD modalities, various ICD inducers, development and application of novel ICD-inducing strategies are summarized. Moreover, the prospects and challenges are briefly outlined to provide reference for future design of novel immunotherapy based on ICD effect.

Manganese-modified biochar promotes Cd accumulation in Sedum alfredii in an intercropping system.

Intercropping of crops with hyperaccumulators is a sustainable method to remediate contaminated soil without impeding agro-production. However, the function of engineered biochar in intercropping systems and its possible influence on cadmium (Cd) accumulation in hyperaccumulators remain unknown. A root box experiment on celery and Sedum alfredii with and without root separation was conducted in this study. Pristine and KMnO4-modified biochar (BCMn) were used to investigate the effects of different biochars on plant growth and Cd uptake in an intercropping system, as well as the influence of engineered biochar on Cd accumulation in hyperaccumulators. The results demonstrated that soil pH did not significantly vary with biochar application in the root separation treatment. However, BCMn significantly increased soil pH and thus reduced available Cd when the plant roots were not separated. Intercropping (no separation treatment) led to a 34% higher and 24% lower aboveground biomass of celery and S. alfredii, respectively, regardless of biochar addition. Compared with aboveground plant parts, plant roots exhibited more significant responses to biochar. Interestingly, intercropping may favour the phytoextraction of Cd by S. alfredii. In particular, the Cd uptake by S. alfredii roots substantially increased (118-187%), whereas that of celery roots decreased (51-71%) with BCMn addition, compared with other treatments. Moreover, after BCMn addition the accumulation of Cd in aboveground S. alfredii in the no separation treatment was 136% higher than that in the separation treatment. This was possibly related to the interaction of manganese (Mn) with Cd as well as the roots of S. alfredii. These findings provide new insights into the application of engineered biochar for phytoextraction, which is important for the efficient remediation of Cd-contaminated soils.

Management and prognosis comparison between incidental and nonincidental intravenous leiomyomatosis: a retrospective single-center real-life experience.

Background: Intravenous leiomyomatosis (IVL) is a rare, difficult-to-treat type of smooth muscle tumor that originates from the uterine myoma. However, its clinical characteristics, management, and prognosis are not clearly understood. Moreover, the 2 different methods used to diagnose IVL-incidental and nonincidental-result in completely different treatments. Methods: We conducted a single-center, retrospective study. Our real-life case series included patients pathologically diagnosed with IVL between July 2011 and December 2020. All patients with IVL were divided into 2 groups: an incidental group and a nonincidental group. Medical records of patients, including clinical characteristics, primary treatment, treatment after recurrence, and prognosis, were reviewed. Results: A total of 39 patients were included in the study, with a median patient age of 47 years. Of the 39 cases, 15 (38.5%) were incidentally diagnosed with only intrapelvic tumors. Among the 24 patients with IVL in the nonincidental group, tumor spread in the inferior vena cava, right heart, and pulmonary artery was identified in 4, 17, and 3 patients, respectively. The most common symptoms were abnormal uterine bleeding in the incidental group and chest distress and dyspnea in the nonincidental group. Among the 15 patients in the incidental group, ovary-preserving surgery was performed in 6 young women (≤40 years old), of whom 3 underwent myomectomy. All 24 patients with IVL in the nonincidental group underwent thrombectomy without uterine or ovary preservation by multidisciplinary surgical treatment. Only 1 patient in each group underwent postoperative adjuvant therapy. During the median follow-up of 36.0 months, recurrence was recorded in 5 (12.8%) cases in the incidental group, with no deaths recorded. Only 1 patient was lost to follow-up. No recurrence was noted in the cases in the nonincidental group. Among the 5 patients who experienced recurrence, 4 received secondary surgical treatment and 1 received hormone therapy. All patients were alive as of this report. Conclusions: Patients with IVL who are diagnosed incidentally have a higher recurrence risk than those who are diagnosed nonincidentally and undergo complete tumor resection. However, patients incidentally diagnosed with IVL can still experience long disease-free survival rates following secondary surgical treatment after recurrence.

Immune Subtypes Characterization Identifies Clinical Prognosis, Tumor Microenvironment Infiltration, and Immune Response in Ovarian Cancer.

Objective: Because of the modest immunotherapeutic response among ovarian carcinoma (OC) patients, it is significant to evaluate antitumor immune response and develop more effective precision immunotherapeutic regimens. Here, this study aimed to determine diverse immune subtypes of OC. Methods: This study curated the expression profiles of prognostic immunologically relevant genes and conducted consensus clustering analyses for determining immune subtypes among OC patients in TCGA cohort. With Boruta algorithm, characteristic genes were screened for conducting an immune scoring system through principal component analysis algorithm. The single-sample gene set enrichment analysis and ESTIAMTE methods were adopted for quantifying the immune infiltrates and responses to chemotherapeutic agents were estimated with pRRophetic algorithm. Two immunotherapeutic cohorts were used for investigating the efficacy of immune score in predicting therapeutic benefits. Results: Two immune subtypes were conducted among 377 OC patients. Immune subtype 2 was characterized by worse clinical prognosis, more frequent genetic variations and mutations, enhanced immune infiltrates, and increased expression of MHC molecules and programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1). In total, 30 prognosis-relevant characteristic immune subtype-derived genes were identified for constructing the immune score of OC patients. High immune score was linked with more dismal prognosis, decreased immune infiltrations, and expression of MHC molecules. High immune score presented favorable sensitivity to doxorubicin and vinorelbine and reduced sensitivity to cisplatin. In addition, immune score possessed the potential in predicting benefits from anti-PD-1/PD-L1 therapy. Conclusion: Collectively, our findings propose two complex and diverse immune subtypes of OC. Quantitative assessment of immune subtypes in individual patients strengthens the understanding of tumor microenvironment features and promotes more effective immunotherapeutic regimens.

Immobilization of Lead and Cadmium in Soil Using Biochars Derived from Pig Manure and Suaeda glauca.

Biochar was for the first time produced from Suaeda glauca. The immobilization of Pb and Cd by this biochar and pig manure biochar was examined in two types of soils by diethylene triamine pentaacetic acid (DTPA) extraction. Addition of biochars decreased DTPA extractable Pb and Cd in Fluvo-aquic soil with reduction rates being 11.3%-48.4% and 0.74%-64.9% compared with the control treatment. The pig manure biochar favored the immobilization of Pb and S. glauca biochar favored the immobilization of Cd. Biochars can effectively immobilize heavy metals in Fluvo-aquic soil. However, the addition of biochars increased extractable Pb and Cd in red soil, with pig manure biochars showing greater rates. This is ascribed to that the competition effects of ions released from biochar enhanced the moving of heavy metals from iron and manganese oxides bound form to organic matter bound form, and hence enhanced the mobility and bioavailability of heavy metals.

Highly expressed NRSN2 is related to malignant phenotype in ovarian cancer.

Neurensin-2 (NRSN2) is a 24KD protein, which is reported located in the membrane, while its biological functions remain unknown, not to mention in the field of tumor biology. In current study, we aimed to analyze the functions of NRSN2 in ovarian cancer. We screened TCGA database and surprisingly found that its copy number and mRNA level are gained and heightened respectively in parts of serous ovarian cancer patients. In current study, both loss- and gain- function assays found that NRSN2 is associated with the malignant phenotype in ovarian cancer cells, because NRSN2 plays a remarkable role in anchorage-independent colony formation, subcutaneous tumor formation, cell invasion, and chemoresistance. Furthermore, we found that the level of NRSN2 was positively correlated with the expression of stem cell marker CD133. In addition, Wnt canonical signaling and Twist/Akt/Erk axis were also regulated by NRSN2. In conclusion, we found that a poorly studied protein, NRSN2, which is associated with the malignant phenotype of serous ovarian cancer and as a membrane protein; it could be a target for serous ovarian cancer treatment.