课程文献中心 更多>>

关键词： Immunological memory   SARS-CoV-2   Viral infection  

关键词： carcinoma of unknown primary   cervical intraepithelial neoplasia   human papillomavirus   squamous cell carcinoma   synchronous cancer   TP53  

摘要： We report a case of synchronous high-grade cervical intraepithelial neoplasia (CIN) and metastatic squamous cell carcinomas (SCCs) of unknown primary in the rectum. A 74-year-old woman was diagnosed with CIN3 by biopsy of the uterine cervix. Magnetic resonance imaging showed two masses in the outer rectal wall. They were diagnosed as SCCs by transrectal biopsy from one mass. On surgical treatment, CIN3 and SCCs in the rectum were identified, respectively. Pathological analysis revealed that SCCs were observed in serosa of the rectum, not mucosa, indicating that these tumors were metastatic SCCs. Gene analysis showed HPV31-positive and TP53 mutation in CIN3, and HPV16-positive in rectal SCCs. Pretreatment examination did not detect the primary site of metastatic SCCs in the rectum. We diagnosed the patient with synchronous CIN3 and metastatic SCCs of unknown primary in the rectum. In this case, gene analysis was useful to clarify the relationship between CIN3 and SCCs.

关键词： miR-101   Cyclooxygenase-2 (COX-2)   Endoplasmic reticulum (ER) stress   Cardiovascular dysfunction   Human umbilical vein endothelial cells    (HUVECs)  

摘要： Exposure to toxic metal contaminants, such as cadmium compounds (Cd2+), has been shown to induce adverse effects on various organs and tissues. In particular, blood vessels are severely impacted by Cd2+ exposure, which may lead to cardiovascular diseases (CVDs). According to previous studies, CVDs are associated with increased cyclooxygenase 2 (COX-2) levels. However, the mechanisms by which CdCl2-induced COX-2 overexpression leads to cardiovascular dysfunction remain unclear. Herein, we show that the relative gene expressions of VEGF and PTGS2 (COX-2 encoding gene) are positively correlated in CVDs patients. Moreover, we demonstrate that the in vitro administration of CdCl2 induces cytotoxicity and endoplasmic reticulum (ER) stress in primary human umbilical vein endothelial cells (HUVECs). The induction of ER stress and the overexpression of COX-2 in CdCl2treated cells alters the protein level of vascular endothelial growth factor (VEGF), resulting in abnormal angiogenesis and increased cytotoxicity. At the pre-transcription level, the inhibition of ER stress by siGRP78 (a key mediator of ER stress) can restore normal angiogenesis in the CdCl2-exposed cells. Meanwhile, at the transcription level, the adverse effects of CdCl2 exposure may be reversed via genetic modification with siRNA (siPTGS2) or by using phytochemical inhibitors (parthenolide, PN) of COX-2. Finally, at the post-transcription level, COX-2 expression may be restricted by the binding of microRNA-101 (miR-101) to the 3 '-UTR of PTGS2 mRNA. The use of mimic miR-101 (mi101) to induce the expression of miR-101 eventually leads to reduced COX2 protein levels, relieved ER stress, and less abnormal angiogenesis and cytotoxicity of CdCl2-exposed primary HUVECs. Overall, our results suggest that CdCl2-induced abnormal angiogenesis is mediated by miR-101/COX-2/ VEGF-axis-dependent ER stress, and that cardiovascular dysfunction may be controlled by manipulating COX-2 at the pre-transcription, transcription, a

关键词： Tim-3   Primary biliary cholangitis   NK cells   CXCR1   CXCR3  

摘要： Tim-3, which is expressed on a variety of innate immune cells including NK cells, plays a key role in many autoimmune diseases. However, the immunomodulatory actions of Tim-3 on NK cells in primary biliary cholangitis (PBC) remain uncertain. Using a murine model of PBC we evaluated the expression of Tim-3 and its ligand Gal-9 in peripheral blood, liver, and spleen. Additionally, we studied Tim-3 regulation of chemokine receptors (CXCR1 and CXCR3) in vitro. Flow cytometric analysis indicated large numbers of infiltrating NK cells in the liver which exhibited high expression of Tim-3 and CXCR3. Moreover, we found overexpression of CXCR1 in liver tissue and liver-derived NK cells in PBC mice. We also observed lower levels of soluble Tim-3 in the serum of PBC mice. In vitro experiments with liver-derived NK cells from PBC mice indicated that CXCR3 was up-regulated by treatment with recombinant mouse TIM-3 Fc (rmTim-3 Fc) to activate the Tim-3 pathway. Furthermore, stimulating normal mouse spleen NK cells with poly I:C resulted in elevated expression of CXCR1 and interferon-. release. Nonetheless, adding rmTim-3 Fc or rmGal-9 significantly down-regulated CXCR1 expression and IFN-. release in NK cells activated by poly I:C, proposing a means to exploit the Tim-3 pathway to reverse responses in NK cells. In conclusion, our data demonstrate that dysregulation of Tim-3/Gal-9 is involved in modulating the local immune microenvironment in PBC mice. Our findings highlight the potential of Tim-3 pathway to modulate chemokine responses in NK cells during autoimmunity.

关键词： 水环境  

ISBN: (纸本)9787030692443

摘要： 本书在系统总结国内外水生态功能分区的基础上, 系统介绍适合我国的水生态功能分区体系框架与技术方法, 重点阐述水生态功能分区技术步骤及方法, 以全国为对象, 开展水生态功能分区技术应用示范, 提出全国分区方案及管理思路, 为全国水生态功能分区管理工作的开展提供技术支撑。

关键词： HBV   Primary human hepatocytes   HBV replication   Hepatic stellate cells  

摘要： Primary human hepatocytes (PHHs) are considered the gold standard for the in vitro study of HBV replication as they directly reflect the metabolism and functionality of the human liver. However, several limitations of this system include PHH donor-to-donor variability, limited life span and low permissiveness to HBV infection, which precludes long-term infection studies and viral passaging. Here, an easy-to-set-up co-culture platform that combines PHH with hepatic stellate cells (HSCs) was developed. This platform does not rely on chemical supplementation to sustain robust HBV replication and viral antigen secretion making it a more physiologically relevant system for in vitro HBV infection studies compared to the traditional short-lived PHH monocultures.

关键词： Insulin therapy withdrawal   Glucotoxicity   Type 2 diabetes  

摘要： Introduction This study aimed to examine retrospectively the clinical backgrounds of Japanese patients with type 2 diabetes (T2D) who successfully withdrew from insulin use after being started on basal insulin in an outpatient setting. Methods The study population comprised 376 insulin-naive patients who were started on basal insulin (glargine U100, glargine U300, or degludec) for the management of T2D and followed the treatment regimen for at least 6 months in 13 institutions in Japan. The clinical courses of the study participants were compared based on outpatient clinic medical records for the three different types of basal insulin prescribed by categorizing the participants into two groups retrospectively: those who successfully withdrew from insulin therapy and those who did not, during a 6-month observation period. The clinical determinants for insulin withdrawal were assessed using a Cox proportional hazard model. Results Glycated hemoglobin was improved in all participants regardless of basal insulin type. Of the 376 study participants, 61 successfully withdrew from basal insulin therapy. After adjustment was made for several confounders, the positive determinant factors for successful withdrawal of insulin were short duration of diabetes and high body mass index at the start of study, and the negative determinant factor was use of insulin secretagogues at the start. The types of basal insulin used by the study participants were not significant determinants of successful insulin withdrawal in this study. Conclusions Use of basal insulin is a powerful option for the treatment of T2D. In patients with high BMI and/or short duration of diabetes, short-term insulin therapy is a promising strategy for the treatment of T2D before the initiation of insulin secretagogues, since such patients have the potential to successfully withdraw from basal insulin use even in an outpatient setting.

关键词： multiple myeloma   tunneling nanotube   mitochondrial transfer   cancer drug resistance   bone marrow mesenchymal stromal cell  

摘要： Simple Summary Mitochondrial transfer plays a crucial role in the acquisition of drug resistance in multiple myeloma, but its exact mechanism is not yet clear;moreover, overcoming the drug resistance that it causes is also a major challenge. Our research on primary myeloma cell cultures reveals that mitochondrial transfer is bi-directional between bone marrow stromal cells and myeloma cells, occurring via tunneling nanotubes and partial cell fusion with extreme increases under the influence of chemotherapeutic drugs, whereupon survival and adenosine triphosphate levels increase, while mitochondrial superoxide levels decrease in myeloma cells. These changes and the elevation of superoxide levels in stromal cells are proportional to the amount of incorporated mitochondria derived from the other cell type and to the concentration of the used drug. Although the inhibition of mitochondrial transfer is limited between stromal and myeloma cells, the supportive effect of stromal cells can be effectively averted by influencing the tumor metabolism with an inhibitor of oxidative phosphorylation in addition to chemotherapeutics. Recently, it has become evident that mitochondrial transfer (MT) plays a crucial role in the acquisition of cancer drug resistance in many hematologic malignancies;however, for multiple myeloma, there is a need to generate novel data to better understand this mechanism. Here, we show that primary myeloma cells (MMs) respond to an increasing concentration of chemotherapeutic drugs with an increase in the acquisition of mitochondria from autologous bone marrow stromal cells (BM-MSCs), whereupon survival and adenosine triphosphate levels of MMs increase, while the mitochondrial superoxide levels decrease in MMs. These changes are proportional to the amount of incorporated BM-MSC-derived mitochondria and to the concentration of the used drug, but seem independent from the type and mechanism of action of chemotherapeutics. In parallel, BM-MSCs also incorpor

关键词： Acinic cell carcinoma   Mandible   Salivary gland tumor   Head and neck  

摘要： Introduction and importance: Acinic cell carcinoma (ACC) is a rare low-grade salivary gland malignancy that accounts for approximately 17% of all salivary gland malignancies. The most common site affected by ACC is the parotid gland followed by the submandibular glands, minor salivary glands, and sublingual glands. Also, it could hardly be observed in unusual sites such as the jaw bones. Case presentation: This case is an example of a central acinic cell carcinoma in a 73-year-old man who came up with a painless gradual swelling for 15 months. Based on clinico-radio-pathologic findings, the diagnosis of a solid variant Intraosseous Acinic Cell Carcinoma was established. Subsequently, the patient underwent hemimandibulectomy and modified radical neck dissection, followed by postoperative radiotherapy. Within a sixmonth follow-up period, no evidence of residual tumor was found. Clinical discussion: Central salivary gland carcinoma is a rare entity and intraosseous ACC is more scarcely observed. Based on our findings, a total of 17 cases of primary intraosseous ACC have been reported so far. Etiology and clinical presentations of this tumor are still vague due to its rarity. Conclusion: Dentists and oral surgeons must be aware of such a rare malignant lesion when encountering a radiolucent lesion within the jaws. The early diagnosis and a complete surgical excision to achieve tumor-free surgical margins and a long-term follow-up could result in significantly improved survival rates.

关键词： Squamous cell carcinoma   Secondary primary carcinoma   Pectoralis major myocutaneous flap   Oral cavity   Metaplastic transformation  

摘要： A 54-year-old man presented with a second primary tongue squamous cell carcinoma, which developed in the pectoralis major myocutaneous flap used for the reconstruction of the right side of the tongue 20 years previously. The patient had originally undergone concurrent chemoradiotherapy and subtotal glossectomy. We believe that the carcinoma was likely caused by metaplastic transformation of the flap skin due to its chronic exposure to stimuli not normally experienced by the skin. The findings in this case suggest that patient education and long-term follow-up are required following flap reconstruction in cases of advanced oral cancer. (C) 2021 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.