Search

Background: Thyroid cancer is one of the most common cancers in the world. Genetic factors are important in the occurrence and development of thyroid cancer, and genetic diagnosis has become an important basis for the prognosis of benign and malignant nodules. We identify a family of six siblings with inherited thyroid cancer susceptibility. All six members of this generation have been definitely diagnosed with papillary thyroid carcinoma. This work aims at confirming the relevant causative genes for thyroid cancer in this pedigree., Methods: We extract DNA from the peripheral blood of six individuals and perform whole genome sequencing. Sanger sequencing and immunohistochemistry further testify the cathepsin F (CTSF) mutation and expression., Results: We identify 57 single nucleotide variations (SNVs) out of at least 4 affected family members via certain filter criteria. The CTSF gene found in five of the six family members is here considered the most promising candidate gene mutation for familial thyroid cancer. Besides, our research also proves several known genes including CTSB, TEKT4, ESR1, MSH6, DIRC3, GNAS, and BANCR that act as probable oncogenic drivers in this family. The Sanger sequencing identifies the existence and veracity of CTSF somatic mutations. The CTSF immunohistochemistry of thyroid cancer tissue specimens displays that higher CTSF expression in mutated patients than that in wild-type patient as well as pericarcinomatous tissue., Conclusions: We conclude that the evaluation of CTSF gene mutations of patients in thyroid cancer families may be predictive and valuable for the familial heredity of thyroid cancer., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (Copyright © 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

An Mg-Zn-Ca-Y alloy operative clip was developed to overcome the drawbacks of the Ti clips such as ion dissolution inflammation, interference imaging diagnosis, and the potential harm that permanent retention brings to the patient. The structure optimization design of the hemostatic clip was carried out by the finite element numerical simulation method to realize the matching between the structure design and the material properties. Hot extrusion and wire cutting process was used to prepare the Mg-Zn-Ca-Y alloy operative clip. Corrosion degradation behavior of Mg-Zn-Ca-Y alloy in vitro was investigated using electrochemical noise (EN) and immersion test in Simulated body fluid (SBF). The carotid artery of SD rats was clipped using the Mg-Zn-Ca-Y operative clip to evaluate occlusion safety and the complete corrosion degradation behavior and biocompatibility of Mg-Zn-Ca-Y alloy clip in vivo were investigated using micro-computed tomography, histological analysis, and blood biochemical indicators. It was found that the newly designed Mg-Zn-Ca-Y clip can successfully ligate the carotid artery, and no blood leakage occurred after surgery. After eight months, the Mg-Zn-Ca-Y clip degraded utterly. Histological analysis and various blood biochemical parameters in SD rat serum samples collected at different time periods showed no tissue inflammation around the clips., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Gastric cancer is a common malignant tumor in the clinic with a high mortality rate, ranking the first among malignant tumors of the digestive system. Early gastric cancer exhibits no specific clinical symptoms and signs, and most of the patients were diagnosed as advanced gastric cancer. The prognosis is poor, and the 5-year overall survival rate is still lower than 30%, seriously threatening people's life and health. However, the pathogenesis of gastric cancer is still unclear., Methods: This study aimed to identify methylated differentially expressed genes in gastric cancer and to study the cellular functions and pathways that may be involved in its regulation, as well as the biological functions of key methylated differentially expressed genes. The gene expression data set and methylation data set of gastric cancer genes based on TCGA were analyzed to identify prognostic methylated genes., Results: This study showed that the methylation of the DERL3 promoter was correlated with the clinical analysis of tumors. Further studies were conducted on genes co-expressed with DERL3, whose functions and pathways to inhibit gastric cancer were adaptive immune response, T cell activation, immune response-regulating pathway, cell surface on molecules, and natural killer cell-mediated cytotoxicity. Finally, cell proliferation assay, cell scratch assay, and cell invasion assay confirmed that DERL3 as a tumor suppressor gene inhibited the malignant evolution of gastric cancer., Conclusions: The analysis of key methylated differentially expressed genes helped elucidate the epigenetic regulation mechanism in the development of gastric cancer. DERL3, as a methylation biomarker, has a predictive and prognostic value in the accurate diagnosis and treatment of gastric cancer and provides potential targets for the precision treatment of gastric cancer., Trial Registration: Not applicable., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Interleukin-35 (IL-35) has recently been identified as an immunosuppressive cytokine that has been used as a potential therapy for chronic inflammatory and autoimmune diseases. However, there remains a paucity of data regarding its potential benefits after integration into mesenchymal stem cells (MSCs)., Methods: We used a dextran sulfate sodium (DSS)-induced colitis mice model and treated them with IL-35-MSCs, MSCs or saline. The body weight was recorded daily and inflammatory processes were determined. Cytokine secretion by lamina propria lymphocytes (LPLs) and percentage of regulatory T cells (Tregs) were also measured., Results: The data showed that mice in the two treated groups recovered their body weight more rapidly than mice treated with saline in the later stage of colitis. The colon lengths of IL-35-MSC-treated mice were markedly longer than those in the other two groups and the inflammation reduced significantly. Furthermore, the percentage of Foxp3 + Tregs increased significantly and the level of proinflammatory cytokines produced by LPLs decreased significantly in the IL-35-MSC-treated group., Discussion: The results demonstrate that IL-35-MSCs could ameliorate ulcerative colitis by down-regulating the expression of pro-inflammatory cytokines., (Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Mesenchymal stem cells (MSCs) have recently emerged as promising candidates for cell-based immune tolerance therapy. Interleukin 35 (IL-35) is a relatively newly identified cytokine required for the regulatory and suppressive functions of regulatory T cells (Treg), playing an important role in the prevention of autoimmune diseases. In this study, we isolated adipose tissue-derived MSCs, a good vehicle for cell therapy, which were transfected with a lentivirus vector for the overexpression of the therapeutic murine IL-35 gene. IL-35 levels in transfected MSCs (IL-35-MSCs) were quantified by ELISA. Co-culture of CD4 + T cells and IL-35-MSCs resulted in the inhibition of CD4 + T cell proliferation and IL-17A secretion. In addition, IL-35-MSCs induced IL-10 production by CD4 + T cells, but did not affect IFN-γ. These findings suggested that MSCs over-expressing IL-35 had higher immunosuppressive capacity compared with non-transfected MSCs, and may provide a useful approach for basic research on gene therapy for autoimmune disorders., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aims: Midkine is a multifunctional cytokine identified to be a promising cancer biomarker. We aimed to prospectively investigate serum midkine as a diagnostic and prognostic biomarker in differentiated thyroid cancer (DTC)., Main Methods: 162 patients with thyroid nodules participated in the surgical cohort (post-surgical pathology proved 70 cases with DTC and 92 cases with benign thyroid nodules), 75 healthy subjects served as control. Diagnostic values of pre-surgical midkine and thyroglobulin for DTC were conducted by receiver operating characteristic (ROC) curves. 214 DTC patients participated in the (131)I treatment cohort. Prognostic values of pre-(131)I-ablative midkine and thyroglobulin to predict (131)I-avid metastases were performed by ROC curves. Metastasis-free survival was analyzed by the Kaplan-Meier method., Key Findings: Much better diagnostic capability of midkine than thyroglobulin was shown to differentiate DTC from benign thyroid nodules, with cut-off midkine value of 323.12pg/ml and diagnostic accuracy of 75.31%. Nearly similar diagnostic capabilities of midkine and thyroglobulin were shown to distinguish DTC from normal participants. Pre-(131)I-ablative thyroglobulin demonstrated perfect ability to predict metastases, with cut-off value and diagnostic accuracy of 19.50ng/ml and 96.73%. Midkine also performed well with a cut-off value and diagnostic accuracy of 504.71pg/ml and 89.25%. DTC patients with midkine or thyroglobulin levels higher than those of thresholds (500pg/ml or 20ng/ml) showed a significantly worse (131)I-avid metastasis-free survival by the Kaplan-Meier method (P<0.01)., Significance: Our results show that midkine is as good as or even better than thyroglobulin to screen patients with thyroid nodules for DTC before surgery, and to predict whether metastases exist before the first (131)I ablative therapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aims: Midkine (MK) is a multifunctional cytokine identified to be a promising cancer biomarker. Nuclear factor-kappa B (NF-κB) is an important transcription factor that plays a pivotal role in tumorigenesis. We aimed to investigate values of MK and NF-κB as markers for diagnosis and synchronous metastasis prediction in papillary thyroid cancer (PTC)., Main Methods: 76 cases of PTC and 70 cases of multi-nodular goiter (MNG) were retrieved. The PTC group was further divided into subgroup 1 (16 cases with synchronous metastases) and subgroup 2 (60 cases without metastases). A retrospective review of demographic and clinical information was performed. Immunohistochemistry of MK, NF-κB p65 and Ki-67 was performed on paraffin-embedded specimens and results were quantified. Diagnostic values of the parameters were conducted by receiver operating characteristic (ROC) curves. Protein levels of MK and NF-κB p65 were then confirmed by Western blot., Key Findings: Immunoreactivities of MK, NF-κB p65 and Ki-67 were significantly higher in the PTC group than in the MNG group with good differential diagnostic capabilities. Moreover, immunoreactivities of all three parameters were significantly higher in subgroup 1 than in subgroup 2 with good synchronous metastasis predictive efficacies. Western blot showed that MK and NF-κB p65 protein levels in lesions from subgroup 1 were significantly higher than those from subgroup 2, both of which were significantly higher than in MNG lesions., Significance: We discovered that MK and NF-κB immunohistochemistries can potentially be used for differential diagnosis between PTC and MNG, and for prediction of synchronous metastases., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Regulatory T (Treg) cells play a pivotal role in the maintenance of transplantation tolerance. It is of great interest to induce allograft tolerance mediated by regulatory CD4(+)CD25(+) T cells., Methods: Here we investigated the effect of hydrodynamic IL-35-expressing plasmid injection in combination with a methyltransferase inhibitor (decitabine) on immune function and transplantation tolerance in mice., Results: We showed that IL-35 and decitabine stimulated the proliferation of CD4(+)CD25(+) Tregs and suppressed CD8(+) T cell proliferation in an allogenic mixed lymphocyte culture in vitro. IL-35 gene therapy and decitabine administration prolonged the survival of the transplanted heart in the heterotopic abdominal heart transplantation model in mice., Conclusions: The possible mechanism through which IL-35 and decitabine treatment increased the survival of graft tissues is to enhance the proliferation of CD4(+)CD25(+) Treg cells and suppress the generation and function of effector T cells. Thus, IL-35 gene therapy combined with decitabine provides a novel approach to induce transplantation tolerance., (© 2013.)