MDSCs: Key Criminals of Tumor Pre-metastatic Niche Formation

The emergence of disseminated metastases remains the primary cause of mortality in cancer patients. Formation of the pre-metastatic niche (PMN), which precedes the establishment of tumor lesions, is critical for metastases. Bone marrow-derived myeloid cells (BMDCs) are indispensable for PMN formation. Myeloid-derived suppressor cells (MDSCs) are a population of immature myeloid cells that accumulate in patients with cancer and appear in the early PMN. The mechanisms by which MDSCs establish the pre-metastatic microenvironment in distant organs are largely unknown, although MDSCs play an essential role in metastasis. Here, we summarize the key factors associated with the recruitment and activation of MDSCs in the PMN and review the mechanisms by which MDSCs regulate PMN formation and evolution. Finally, we predict the potential value of MDSCs in PMN detection and therapy

Beneficial effects of baicalein on a model of allergic rhinitis

Allergic rhinitis (AR) is a common disease that causes severe inflammation and even disabilities. Previous studies have reported baicalein to have an anti-inflammatory effect. However, the pharmacological action of baicalein on anaphylaxis has not been clarified yet. This study assessed the in vivo protective effect of baicalein post-treatment in an ameliorating ovalbumin (OVA)-sensitized AR rat model. Baicalein attenuated histological alterations, aberrant tissue repair and inflammation after OVA-induced AR. Baicalein reduced the frequency of nasal/ear rubs and sneezes in rats, and inhibited generation of several inflammatory cytokines (TNF-α, IL-1β, and IL-6) in both blood and nasal lavage of rats. Infiltrations of eosinophils, lymphocyte, and neutrophils were decreased in baicalein-administered rats. Furthermore, baicalein inhibited the expression of STAT3 phosphorylation in the nasal mucosa. In summary, baicalein attenuated OVA-induced AR and inflammation, which suggests it as a promising therapeutic agent for the alleviation of AR-associated inflammation and pathology

Association of p53 rs1042522, MDM2 rs2279744, and p21 rs1801270 polymorphisms with retinoblastoma risk and invasion in a Chinese population.

Single nucleotide polymorphisms (SNPs) of p53 rs1042522, MDM2 rs2279744 and p21 rs1801270, all in the p53 pathway, which plays a crucial role in DNA damage and genomic instability, were reported to be associated with cancer risk and pathologic characteristics. This case-control study was designed to analyse the association between these SNPs and retinoblastoma (RB) in a Chinese Han population. These SNPs in 168 RB patients and 185 adult controls were genotyped using genomic DNA from venous blood. No significant difference was observed in allele or genotypic frequencies of these SNPs between Chinese RB patients and controls (all P > 0.05). However, the rs1042522 GC genotype showed a protective effect against RB invasion, as demonstrated by event-free survival (HR = 0.53, P = 0.007 for GC versus GG/CC). This effect was significant for patients with a lag time >1 month and no pre-enucleation treatment (P = 0.007 and P = 0.010, respectively), indicating an interaction between p53 rs1042522 and clinical characteristics, including lag time and pre-enucleation treatment status. Thus, the rs1042522 SNP may be associated with RB invasion in the Han Chinese population; however, further large and functional studies are needed to assess the validity of this association

High Altitude test of RPCs for the ARGO-YBJ experiment

A 50 m**2 RPC carpet was operated at the YangBaJing Cosmic Ray Laboratory (Tibet) located 4300 m a.s.l. The performance of RPCs in detecting Extensive Air Showers was studied. Efficiency and time resolution measurements at the pressure and temperature conditions typical of high mountain laboratories, are reported.Comment: 16 pages, 10 figures, submitted to Nucl. Instr. Met

Role of myeloid-derived suppressor cells in the promotion and immunotherapy of colitis-associated cancer

Colitis-associated cancer (CAC) is a specific type of colorectal cancer that develops from inflammatory bowel disease (IBD). Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that are essential for the pathological processes of inflammation and cancer. Accumulating evidence indicates that MDSCs play different but vital roles during IBD and CAC development and impede CAC immunotherapy. New insights into the regulatory network of MDSCs in the CAC pathogenesis are opening new avenues for developing strategies to enhance the effectiveness of CAC treatment. In this review, we explore the role of MDSCs in chronic inflammation, dysplasia and CAC and summarize the potential CAC therapeutic strategies based on MDSC blockade

Pure uniportal video-assisted thoracic surgery for treating thoracic tuberculous spondylitis: an initial case series of seven patients

Abstract Background The development of thoracic surgical techniques has provided a new avenue for treating thoracic tuberculosis. Moreover, microscopic treatment of spinal tuberculosis has attracted increasing attention, as it affords good visual access and reduces trauma. Traditional thoracoscopic treatment of spinal tuberculosis usually requires 2–3 passages, accompanied by a corresponding number of incisions. With a large number of conventional thoracoscopic surgeries performed, improved resolution of the microscopic field of view, effective hemostasis of the peripheral vessels using the ultrasonic knife, and many reports in the literature, thoracic tuberculosis can now be treated microscopically by creating a single channel. The aim of this study was to explore the feasibility and surgical technique for thoracic tuberculous spondylitis treatment via debridement and bone graft fusion surgery employing pure uniportal video-assisted thoracic surgery (VATS), combined with posterior internal fixation. Methods Seven patients with relatively complete documentation were included in this study. All patients underwent lesion removal and bone graft reconstruction via uniportal VATS with posterior internal fixation. The mean patient age was 39.6 years. Surgical duration, blood loss volume, postoperative recovery time, and thoracic kyphosis angle were recorded. Results The surgeries were successful with no severe postoperative complications. All patients were followed-up, and no recurrence of tuberculosis was observed. Imaging data, including computed tomography scans, confirmed the complete removal of the lesions. Additionally, bone fusion at the graft site was successful, no loss of the thoracic kyphosis angle was noted postoperatively, and the thoracic kyphosis angle improved. Conclusions Pure uniportal VATS yields satisfactory results and inflicts less trauma than previous surgical techniques. This technique also offers a reference value for treating thoracic tuberculous spondylitis

Effectiveness of Rain Classroom Intelligent Teaching Design: A Case Study of the Course of Spring Water Tourism Resources

[Objectives] To evaluate the effectiveness of Rain Classroom intelligent teaching in the course of Spring Water Tourism Resources. [Methods] The course of Spring Water Tourism Resources in the course of Overview of Tourism Resources was taken as an example, the pre-class preparation, in-class teaching, and after-class evaluation links were designed separately through the Rain Classroom platform. Then, a questionnaire survey was carried out for the students of Spring Water Tourism Resources. [Results] About 58.3% of the students believed that the greatest advantage of using the Rain Classroom teaching platform is that the learning method is flexible and can improve the ability of independent learning; 61.78% of students stated that playing 3D animation in the classroom has the best effect for learning different tourism resources; with the aid of the Rain Classroom platform, the communication between teachers and students becomes more timely, and the students' ability to deal with practical problems can be practiced. [Conclusions] This study is intended to build an intelligent classroom model suitable for tourism management department based on the Rain Classroom platform. It is recommended to promote and apply this model in the teaching of tourism management

G-MDSC-derived exosomes mediate the differentiation of M-MDSC into M2 macrophages promoting colitis-to-cancer transition

Backgrounds In inflammatory bowel disease microenvironment, transdifferentiation of myeloid-derived suppressor cells (MDSCs) and M2 macrophage accumulation are crucial for the transition of colitis-to-cancer. New insights into the cross-talk and the underling mechanism between MDSCs and M2 macrophage during colitis-to-cancer transition are opening new avenues for colitis-associated cancer (CAC) prevention and treatment.Methods The role and underlying mechanism that granulocytic MDSCs (G-MDSCs) or exosomes (Exo) regulates the differentiation of monocytic MDSCs (M-MDSCs) into M2 macrophages were investigated using immunofluorescence, FACS, IB analysis, etc, and employing siRNA and antibodies. In vivo efficacy and mechanistic studies were conducted with dextran sulfate sodium-induced CAC mice, employed IL-6 Abs and STAT3 inhibitor.Results G-MDSCs promote the differentiation of M-MDSC into M2 macrophages through exosomal miR-93–5 p which downregulating STAT3 activity in M-MDSC. IL-6 is responsible for miR-93–5 p enrichment in G-MDSC exosomes (GM-Exo). Mechanistically, chronic inflammation-driven IL-6 promote the synthesis of miR-93–5 p in G-MDSC via IL-6R/JAK/STAT3 pathway. Early use of IL-6 Abs enhances the effect of STAT3 inhibitor against CAC.Conclusions IL-6-driven secretion of G-MDSC exosomal miR-93–5 p promotes the differentiation of M-MDSC into M2 macrophages and involves a STAT3 signaling mechanism that promote colitis-to-cancer transition. Combining STAT3 inhibitors with strategies that inhibit IL-6-mediated G-MDSC exosomal miR-93–5 p production is beneficial for the prevention and treatment of CAC