Single-cell and spatial transcriptomics reveal metastasis mechanism and microenvironment remodeling of lymph node in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor and is highly prone to metastasis. OS can metastasize to the lymph node (LN) through the lymphatics, and the metastasis of tumor cells reestablishes the immune landscape of the LN, which is conducive to the growth of tumor cells. However, the mechanism of LN metastasis of osteosarcoma and remodeling of the metastatic lymph node (MLN) microenvironment is not clear. METHODS: Single-cell RNA sequencing of 18 samples from paracancerous, primary tumor, and lymph nodes was performed. Then, new signaling axes closely related to metastasis were identified using bioinformatics, in vitro experiments, and immunohistochemistry. The mechanism of remodeling of the LN microenvironment in tumor cells was investigated by integrating single-cell and spatial transcriptomics. RESULTS: From 18 single-cell sequencing samples, we obtained 117,964 cells. The pseudotime analysis revealed that osteoblast(OB) cells may follow a differentiation path from paracancerous tissue (PC) → primary tumor (PT) → MLN or from PC → PT, during the process of LN metastasis. Next, in combination of bioinformatics, in vitro and in vivo experiments, and immunohistochemistry, we determined that ETS2/IBSP, a new signal axis, might promote LN metastasis. Finally, single-cell and spatial dissection uncovered that OS cells could reshape the microenvironment of LN by interacting with various cell components, such as myeloid, cancer-associated fibroblasts (CAFs), and NK/T cells. CONCLUSIONS: Collectively, our research revealed a new molecular mechanism of LN metastasis and clarified how OS cells influenced the LN microenvironment, which might provide new insight for blocking LN metastasis.

Real-world setting comparison of bridging therapy versus direct mechanical thrombectomy for acute ischemic stroke: A meta-analysis

Abstract Background and purpose Intravenous Thrombolysis (IVT) prior to Mechanical Thrombectomy (MT) for Acute Ischaemic Stroke (AIS) due to Large-Vessel Occlusion (LVO) remains controversial. Therefore, the authors performed a meta-analysis of the available real-world evidence focusing on the efficacy and safety of Bridging Therapy (BT) compared with direct MT in patients with AIS due to LVO. Methods Four databases were searched until 01 February 2023. Retrospective and prospective studies from nationwide or health organization registry databases that compared the clinical outcomes of BT and direct MT were included. Odds Ratios (ORs) and 95 % Confidence Intervals (CIs) for efficacy and safety outcomes were pooled using a random-effects model. Results Of the 12 studies, 86,695 patients were included. In patients with AIS due to LVO, BT group was associated with higher odds of achieving excellent functional outcome (modified Rankin Scale score 0-1) at 90 days (OR = 1.48, 95 % CI 1.25-1.75), favorable discharge disposition (to the home with or without services) (OR = 1.33, 95 % CI 1.29-1.38), and decreased mortality at 90 days (OR = 0.62, 95 % CI 0.56-0.70), as compared with the direct MT group. In addition, the risk of symptomatic intracranial hemorrhage did not increase significantly in the BT group. Conclusion The present meta-analysis indicates that BT was associated with favorable outcomes in patients with AIS due to LVO. These findings support the current practice in a real-world setting and strengthen their validity. For patients eligible for both IVT and MT, BT remains the standard treatment until more data are available.

Cascades between miRNAs, lncRNAs and the NF-κB signaling pathway in gastric cancer (Review).

Gastric cancer is a common digestive tract malignancy that is mainly treated with surgery combined with perioperative adjuvant chemoradiotherapy and biological targeted therapy. However, the diagnosis rate of early gastric cancer is low and both postoperative recurrence and distant metastasis are thorny problems. Therefore, it is essential to study the pathogenesis of gastric cancer and search for more effective means of treatment. The nuclear factor-κB (NF-κB) signaling pathway has an important role in the occurrence and development of gastric cancer and recent studies have revealed that microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are able to regulate this pathway through a variety of mechanisms. Understanding these interrelated molecular mechanisms is helpful in guiding improvements in gastric cancer treatment. In the present review, the functional associations between miRNAs, lncRNAs and the NF-κB signaling pathway in the occurrence, development and prognosis of gastric cancer were discussed. It was concluded that miRNAs and lncRNAs have complex relations with the NF-κB signaling pathway in gastric cancer. miRNAs/target genes/NF-κB/target proteins, signaling molecules/NF-κB/miRNAs/target genes, lncRNAs/miRNAs/NF-κB/genes or mRNAs, lncRNAs/target genes/NF-Κb/target proteins, and lncRNAs/NF-κB/target proteins cascades are all important factors in the occurrence and development of gastric cancer.

14-3-3 σ: A potential biomolecule for cancer therapy.

As more studies have focused on the function of 14-3-3 proteins, their role in tumor progression has gradually improved. In the 14-3-3 protein family, 14-3-3σ is the protein that is most associated with tumor occurrence and development. In some malignancies, 14-3-3σ acts as a tumor suppressor via p53 and tumor suppressor genes. In most tumors, 14-3-3σ overexpression increases resistance to chemotherapy and radiotherapy and mediates the G2-M checkpoint after DNA damage. Although 14-3-3σ overexpression has been closely associated with poorer prognosis in pancreatic, gastric and colorectal cancer, its role in gallbladder and nasopharyngeal cancer remains less clear. As such, the function of 14-3-3σ in specific cancer types needs to be further clarified. It has been hypothesized that a role may be related to its molecular chaperone function combined with various protein ligands. In this review, we examine the role of 14-3-3σ in tumor development and drug resistance. We discuss the potential of targeting 14-3-3σ regulators in cancer therapy and treatment.

Pre etched Ag nanocluster as SERS substrate for the rapid quantification of AFB1 in peanut oil via DFT coupled multivariate calibration.

The current study extends the use of surface-enhanced Raman spectroscopy (SERS) combined with density functional theory (DFT) and multivariate calibration towards the rapid quantification of aflatoxin B1 (AFB1) in peanut oil samples. It reports the design of pre etched Ag nanocluster as an active SERS substrate for quantifying AFB1, after being impregnated on its surface. The SERS spectra of AFB1@pre etched Ag nanocluster was recorded and its respective theoretical spectrum was calculated by density functional theory (DFT) to assign the characteristic peaks. The baseline drift and rotation effects were masked by the first-order derivative preprocessing method followed by multivariate calibration. The BP-AdaBoost model exhibited optimum prediction (Rp = 0.9283 and 0.9332) ability over the concentration range 5-100 and 100-1000 ngmL-1, respectively. The limit of detection calculated was 5.0 ngmL-1 and the obtained recoveries were in the range from 90.4% to 113.1% in spiked peanut oil samples. Additionally, precision analysis revealed an RSD ca. 5%, suggesting the applicability of the pre etched Ag nanocluster SERS substrate towards AFB1 detection. Thus, the proposed SERS platform exploiting DFT and BP-AdaBoost model was found reproducible for the quantification of AFB1 in peanut oil.

Circular RNAs in nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a geographical distributed epithelial tumor of head and neck, which is prevalent in east Africa and Asia, especially southern China. Moreover, NPC has an unfavorable clinical effect and is prone to metastasis at an advanced stage. Although the recovery rate of patients has been improved due to concurrent chemoradiotherapy, poor curative effects and low overall survival remain key issues. The precise mechanisms and pivotal regulators of NPC remain still unclear. To improve the therapeutic efficacy, we focused on related-NPC circular RNAs (circRNAs). CircRNAs are a unique type of endogenous non-coding RNAs (ncRNAs) with a covalent closed-loop structure. Their expression is rich, stable and conservative. Different circRNA have specific tissue and developmental stages and can be detected in body fluids. In addition, circRNAs are involved in multiple pathological processes, especially in cancers. In recent years, using high-throughput indicator technology and bioinformatics technology, a large number of circRNAs have been identified in NPC cells and verified to have biological functions and mechanisms of action. This article aims to provide a retrospective review of the latest research on the proliferation and migration of related-NPC circRNA. Specifically, we focused on the roles and mechanisms of circRNAs in the development and progression of NPC. CONCLUSION: CircRNA can act as an oncogene or tumor suppressor gene and participate in NPC progression (e.g., proliferation, apoptosis, migration, and invasion). In short, circRNAs have potential as biomarkers for the diagnosis, prognosis and treatment of NPC.

Radio-Susceptibility of Nasopharyngeal Carcinoma: Focus on Epstein- Barr Virus, MicroRNAs, Long Non-Coding RNAs and Circular RNAs.

Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer. As a neoplastic disorder, NPC is a highly malignant squamous cell carcinoma that is derived from the nasopharyngeal epithelium. NPC is radiosensitive; radiotherapy or radiotherapy combining with chemotherapy are the main treatment strategies. However, both modalities are usually accompanied by complications and acquired resistance to radiotherapy is a significant impediment to effective NPC therapy. Therefore, there is an urgent need to discover effective radio-sensitization and radio-resistance biomarkers for NPC. Recent studies have shown that Epstein-Barr virus (EBV)-encoded products, microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), which share several common signaling pathways, can function in radio-related NPC cells or tissues. Understanding these interconnected regulatory networks will reveal the details of NPC radiation sensitivity and resistance. In this review, we discuss and summarize the specific molecular mechanisms of NPC radio-sensitization and radio-resistance, focusing on EBV-encoded products, miRNAs, lncRNAs and circRNAs. This will provide a foundation for the discovery of more accurate, effective and specific markers related to NPC radiotherapy. EBVencoded products, miRNAs, lncRNAs and circRNAs have emerged as crucial molecules mediating the radio-susceptibility of NPC. This understanding will improve the clinical application of markers and inform the development of novel therapeutics for NPC.