Springer Science and Business Media LLC

Absent in melanoma 2 (AIM2) has been reported to be an important inflammasome component that exerts tumor suppression in several tumors. However, whether CCL19/CCR7/AIM2 is involved in the progression of GC still remains unclear. Quantitative real-time and ELISA assay were used to determine the expressions of AIM2, CCL19 and CCR7 in GC tissues and cell lines. CCK-8, Edu staining, flow cytometry, Transwell assay, and tumorigenesis in nude mice were used to explore the function of AIM2 and CCL19 in vitro and in vivo. Apoptosis and inflammation-related biomarkers were detected by Western blot and ELISA assay. H&E staining was used to assess the histological changes in the subcutaneous tumor model. Immunohistochemistry (IHC) was used to evaluate the expression of Ki-67. We found that expression levels of AIM2, CCL19 and CCR7 were obviously lower in early GC tissues than those in progressive GC tissues. In vitro assays revealed that CCL19 treatment could enhance the suppressive effects of AIM2 overexpression on cell proliferation, migration, and invasion through CCR7. An in vivo assay also demonstrated that silencing of AIM2 reversed the suppressive effects of CCL19 on tumor growth. Collectively, CCL19 overexpression significantly inhibited GC cell proliferation and tumor growth in vitro and in vivo by up-regulating the CCR7/AIM2 pathway. Thus, CCL19 activated CCR7/AIM2 signaling pathway and it may be a potential therapeutic approach for GC therapy.

Since December 2019, the novel coronavirus SARS-CoV-2 pandemic (COVID-19) outbroke in Wuhan and spread in China. Here we aimed to investigate the clinical and radiological characteristics of COVID-19 cases. We collected and analyzed the clinical data of 172 hospitalized cases of COVID-19 who were diagnosed via qRT-PCR of nasopharyngeal swabs during January 2020 and February 2020. The chest images were reviewed by radiologists and respirologists. The older patients with COVID-19 in Henan Province had more severe disease and worse prognosis. The male sex, smoking history and Wuhan exposure of patients are not related to the severity or prognosis of COVID-19. Family gatherings were showed among 26.7% of patients. A greater proportion of patients in the severe group suffer from combined chronic diseases. CT results showed that most patients had bilateral lung lesions and multiple lung lobes. The lungs of severe patients are more damaged. Both the infection range and inflammatory factor levels are related to the poor prognosis. Antiviral drugs, immunoglobulin and traditional Chinese medicine are mainly used for the treatment of COVID-19 patients. The discharge rate of COVID-19 patients was 93.0%, and the mortality rate was 2.3%. Case type, lymphocyte ratio grade, and respiratory failure at admission are risk factors for poor prognosis, except for the number of infiltrating lung lobes. The results showed that severe disease process, lymphopenia and respiratory failure are risk factors for the COVID-19.

Evidence has shown that mesenchymal stem cells’ (MSCs) therapy has potential application in treating chronic kidney disease (CKD). In addition, MSCs-derived exosomes can improve the renal function and prevent the progression of CKD. However, the mechanisms by which MSCs-derived exosomes (MSCs-Exo) ameliorate renal fibrosis in CKD remain largely unclear. To mimic an in vitro model of renal fibrosis, rat kidney tubular epithelial cells (NRK52E) were stimulated with transforming growth factor (TGF)-β1. In addition, we established an in vivo model of unilateral ureteric obstruction (UUO)-induced renal fibrosis. Meanwhile, we exploited exosomes derived from MSCs for delivering miR-186-5p agomir into NRK52E cells or kidneys in vitro and in vivo. In this study, we found that level of miR-186-5p was significantly downregulated in TGF-β1-stimulated NRK52E cells and the obstructed kidneys of UUO mice. In addition, miR-186-5p can be transferred from MSCs to NRK52E cells via exosomes. MSCs-delivered miR-186-5p markedly reduced the accumulation of extracellular matrix (ECM) protein, and inhibited epithelial-to-mesenchymal transition (EMT) and apoptosis in TGF-β1-stimulated NRK52E cells. Moreover, exosomal miR-186-5p from MSCs attenuated kidney injury and fibrosis in a UUO mouse model via inhibition of the ECM protein accumulation and EMT process. Meanwhile, dual-luciferase assay showed that miR-186-5p downregulated Smad5 expression via direct binding with the 3′-UTR of Smad5. Collectively then, these findings indicated that exosomal miR-186-5p derived from MSCs could attenuate renal fibrosis in vitro and in vivo by downregulation of Smad5. These findings may help to understand the role of MSCs’ exosomes in alleviating renal fibrosis in CKD.

PEGL-DOX is an excellent treatment for recurrent ovarian cancer that rarely causes side-effects like cardiotoxicity or hair loss, but frequently results in Hand-Foot Syndrome (HFS). In severe cases, it can become necessary to reduce the PEGL-DOX concentration or the duration of the drug therapy, sometimes making it difficult to continue treatment. In this study, we prepared an animal model to compare the effects of DOX versus PEGL-DOX, and we noticed that only treatment with PEGL-DOX resulted in HFS, which led us to conclude that extravasation due to long-term circulation was one of the causes of HFS. In addition, we were able to show that the primary factor leading to the skin-specific outbreaks in the extremities was the appearance of reactive oxygen species (ROS) due to interactions between DOX and the metallic Cu(II) ions abundant in skin tissue. ROS directly disturb the surrounding tissue and simultaneously induce keratinocyte-specific apoptosis. Keratinocytes express the thermoreceptor TRPM2, which is thought to be able to detect ROS and stimulate the release of chemokines (IL-8, GRO, Fractalkine), which induce directed chemotaxis in neutrophils and other blood cells. Those cells and the keratinocytes then undergo apoptosis and simultaneously release IL-1β, IL-1α, and IL-6, which brings about an inflammatory state. In the future, we plan to develop preventative as well as therapeutic treatments by trapping the ROS.

Human cancer cell lines have an essential role in cancer research, but only authentic cell lines should be used as biological models. Authentication testing using short tandem repeat (STR) loci has shown that MGC-803 cells, which were reported to come from gastric adenocarcinoma, are similar to HeLa. In this study, we confirmed that the MGC-803 cell line contains genetic material from HeLa, including genetic sequence from human papilloma virus 18 (HPV18). Additional alleles were present on STR analysis that remained stable after extensive passaging and generation of mono-clones. This behavior is consistent with a hybrid cell line arising from cell–cell fusion. Further genetic analysis revealed that MGC-803 originated from donors with different genetic ancestries, one African (HeLa) and the other Asian. Transcriptomic analysis demonstrated that MGC-803 closely resembles HeLa and another nasopharyngeal–HeLa hybrid cell line CNE-2. Based on these findings, we conclude that MGC-803 is a hybrid cell line derived from HeLa and other cells, the latter derived from a different patient with Asian genetic ancestry.

Việc lựa chọn phương pháp điều trị tốt nhất cho từng bệnh nhân ung thư đã thu hút sự chú ý nhằm cải thiện kết quả lâm sàng. Tiến bộ gần đây trong nuôi cấy organoid có thể dẫn đến sự phát triển của y học cá thể hóa. Khác với các loại thuốc nhắm vào phân tử, hiện chưa có phương pháp dự đoán phản ứng của bệnh nhân đối với hóa trị tiêu chuẩn trong ung thư buồng trứng. Chúng tôi đã chuẩn bị organoid bằng phương pháp spheroid xuất phát từ mô ung thư (CTOS) từ 61 bệnh nhân ung thư buồng trứng với tỷ lệ thành công 100%. Các bài kiểm tra độ nhạy hóa trị cho paclitaxel và carboplatin được thực hiện với tỷ lệ thành công 84% bằng cách sử dụng organoid nguyên phát từ 50 bệnh nhân đã được hóa trị. Một loạt độ nhạy khác nhau đã được quan sát thấy giữa các organoid đối với cả hai loại thuốc. Tất cả bốn organoid kháng trị lâm sàng đều kháng cả hai loại thuốc trong 18 trường hợp mà thông tin phản ứng lâm sàng có sẵn. Năm trong số 18 trường hợp (28%) là kháng kép, tỷ lệ phản ứng của chúng tương thích với tỷ lệ remiss lâm sàng. Carboplatin có độ nhạy cao hơn đáng kể trong các loại tế bào dạng dịch hơn là kiểu tế bào trong suốt (P = 0,025). Chúng tôi đã tạo ra hai dòng organoid, sàng lọc 1135 loại thuốc, và tìm thấy một số loại thuốc có hiệu quả kết hợp tốt hơn với carboplatin so với paclitaxel. Một số loại thuốc, bao gồm afatinib, đã cho thấy hiệu ứng bổ sung với carboplatin. Thí nghiệm độ nhạy organoid không dự đoán được kết quả lâm sàng, cả về thời gian sống không tiến triển lẫn tổng sống sót.