Multiple Signaling Pathways Are Involved in the Interleukine-4 Regulated Expression of DC-SIGN in THP-1 Cell Line

Dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) is an important pattern recognition receptor on dendritic cells (DCs), and its expression shows significant cytological and histological specificity, being interleukine-4 (IL-4) dependent. The signaling pathways through which IL-4 regulates expression of DC-SIGN are still unclear. We used phorbol 12-myristate 13-acetate- (PMA-) differentiated THP-1 cells as the in vitro model of monocyte/macrophage cells to study the signaling pathways involved in IL-4-regulated expression of DC-SIGN. We found that a high expression of DC-SIGN could be induced by IL-4 at the levels of mRNA and cell surface protein. Upregulated expression of DC-SIGN was almost completely blocked by the specific inhibitor of ERK pathway, and partly reduced by the specific inhibitors of JAK-STAT and NF-κB pathways. The activation of the three signaling pathways was directly confirmed by testing the phosphorylation of protein kinase within the cytoplasm and nucleus over time. The analysis of cis-acting elements of DC-SIGN promoter showed that the activity of DC-SIGN promoter without Ets-1 transcription factors binding site almost completely disappeared. Our results demonstrated that multiple signaling pathways are involved in IL-4 induced high expression of DC-SIGN on THP-1 cells, in which ERK pathway is the main signaling pathway and mediated by the Ets-1 transcription factors binding site

Psychological states could affect postsurgical pain after hemorrhoidectomy: A prospective cohort study

BackgroundOpen hemorrhoidectomy is one of the standard procedures for grade IV hemorrhoids. Postsurgical pain is a common problem for patients. We aim to prospectively evaluate potential factors affecting postoperative pain among hemorrhoidectomy patients.MethodsAn observational study was conducted on 360 patients who had undergone Milligan-Morgan open hemorrhoidectomy. Details of the surgery and baseline information were recorded. Preoperative anxiety and depression were analyzed via the self-rating anxiety scale 20 (SAS-20) and self-rating depression scales 20 (SDS-20), respectively. Postoperative pain score was performed daily after surgery until the patient was discharged. The numerical pain score was evaluated by the visual analogue scale (VAS). The association between preoperative psychological states (anxiety or depression) and postoperative pain was analyzed using a generalized additive mixed model.ResultsA total of 340 patients eventually provided complete data and were included in our study. The average age was 43.3 ± 14.4 years, and 62.1% of patients were women. In total, 14.9% of patients had presurgical anxiety and 47.1% had presurgical depression. Postsurgical pain reached a peak point 1–2 days after surgery and went down to a very low level around 4–5 days after surgery. More excision of hemorrhoids could lead to more pain experience after surgery. Presurgical depression was associated with postsurgical pain. Patients who had presurgical depression had higher pain scores after surgery (2.3 ± 1.9 vs. 3.3 ± 1.9, p = 0.025).ConclusionPreoperative depression and the amount of excisional hemorrhoids are positively related to postsurgical pain

Abnormal phenomena in a one-dimensional periodic structure containing left-handed materials

The explicit dispersion equation for a one-dimensional periodic structure with alternative layers of left-handed material (LHM) and right-handed material (RHM) is given and analyzed. Some abnormal phenomena such as spurious modes with complex frequencies, discrete modes and photon tunnelling modes are observed in the band structure. The existence of spurious modes with complex frequencies is a common problem in the calculation of the band structure for such a photonic crystal. Physical explanation and significance are given for the discrete modes (with real values of wave number) and photon tunnelling propagation modes (with imaginary wave numbers in a limited region).Comment: 10 pages, 4 figure

Calibrationless Reconstruction of Uniformly-Undersampled Multi-Channel MR Data with Deep Learning Estimated ESPIRiT Maps

Purpose: To develop a truly calibrationless reconstruction method that derives ESPIRiT maps from uniformly-undersampled multi-channel MR data by deep learning. Methods: ESPIRiT, one commonly used parallel imaging reconstruction technique, forms the images from undersampled MR k-space data using ESPIRiT maps that effectively represents coil sensitivity information. Accurate ESPIRiT map estimation requires quality coil sensitivity calibration or autocalibration data. We present a U-Net based deep learning model to estimate the multi-channel ESPIRiT maps directly from uniformly-undersampled multi-channel multi-slice MR data. The model is trained using fully-sampled multi-slice axial brain datasets from the same MR receiving coil system. To utilize subject-coil geometric parameters available for each dataset, the training imposes a hybrid loss on ESPIRiT maps at the original locations as well as their corresponding locations within the standard reference multi-slice axial stack. The performance of the approach was evaluated using publicly available T1-weighed brain and cardiac data. Results: The proposed model robustly predicted multi-channel ESPIRiT maps from uniformly-undersampled k-space data. They were highly comparable to the reference ESPIRiT maps directly computed from 24 consecutive central k-space lines. Further, they led to excellent ESPIRiT reconstruction performance even at high acceleration, exhibiting a similar level of errors and artifacts to that by using reference ESPIRiT maps. Conclusion: A new deep learning approach is developed to estimate ESPIRiT maps directly from uniformly-undersampled MR data. It presents a general strategy for calibrationless parallel imaging reconstruction through learning from coil and protocol specific data

Decoding the spermatogonial stem cell niche under physiological and recovery conditions in adult mice and humans

The intricate interaction between spermatogonial stem cell (SSC) and testicular niche is essential for maintaining SSC homeostasis; however, this interaction remains largely uncharacterized. In this study, to characterize the underlying signaling pathways and related paracrine factors, we delineated the intercellular interactions between SSC and niche cell in both adult mice and humans under physiological conditions and dissected the niche-derived regulation of SSC maintenance under recovery conditions, thus uncovering the essential role of C-C motif chemokine ligand 24 and insulin-like growth factor binding protein 7 in SSC maintenance. We also established the clinical relevance of specific paracrine factors in human fertility. Collectively, our work on decoding the adult SSC niche serves as a valuable reference for future studies on the aetiology, diagnosis, and treatment of male infertility.</p

Use of MicroRNA Let-7 to Control the Replication Specificity of Oncolytic Adenovirus in Hepatocellular Carcinoma Cells

Highly selective therapy for hepatocellular carcinoma (HCC) remains an unmet medical need. In present study, we found that the tumor suppressor microRNA, let-7 was significantly downregulated in a proportion of primary HCC tissues (12 of 33, 36.4%) and HCC cell lines. In line with this finding, we have engineered a chimeric Ad5/11 fiber oncolytic adenovirus, SG7011let7T, by introducing eight copies of let-7 target sites (let7T) into the 3′ untranslated region of E1A, a key gene associated with adenoviral replication. The results showed that the E1A expression (both RNA and protein levels) of the SG7011let7T was tightly regulated according to the endogenous expression level of the let-7. As contrasted with the wild-type adenovirus and the control virus, the replication of SG7011let7T was distinctly inhibited in normal liver cells lines (i.e. L-02 and WRL-68) expressing high level of let-7 (>300 folds), whereas was almost not impaired in HCC cells (i.e. Hep3B and PLC/PRF/5) with low level of let-7. Consequently, the cytotoxicity of SG7011let7T to normal liver cells was successfully decreased while was almost not attenuated in HCC cells in vitro. The antitumor ability of SG7011let7T in vivo was maintained in mice with Hep3B xenograft tumor, whereas was greatly decreased against the SMMC-7721 xenograft tumor expressing a high level of let-7 similar with L-02 when compared to the wild-type adenovirus. These results suggested that SG7011let7T may be a promising anticancer agent or vector to mediate the expression of therapeutic gene, broadly applicable in the treatment for HCC and other cancers where the let-7 gene is downregulated

A Novel Testis-specific GTPase Serves as a Link to Proteasome Biogenesis: Functional Characterization of RhoS/RSA-14-44 in Spermatogenesis

We functionally characterized RhoS/RSA-14-44 as a new member of Rho GTPase subfamily in spermatogenesis, which provides a direct link between Rho family GTPase and the proteasome biogenesis