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MDR1 is highly expressed in MDR A2780DX5 ovarian cancer cells, MDR SGC7901R gastric cancer cells and recurrent tumours. It pumps cytoplasmic agents out of cells, leading to decreased drug accumulation in cells and making cancer cells susceptible to multidrug resistance. Here, we identified that miR‐495 was predicted to target ABCB1, which encodes protein MDR1. To reduce the drug efflux and reverse MDR in cancer cells, we overexpressed a miR‐495 mimic in SGC7901R and A2780DX cells and in transplanted MDR ovarian tumours in vivo. The results indicated that the expression of MDR1 in the above cells or tumours was suppressed and that subsequently the drug accumulation in the MDR cells was decreased, cell death was increased, and tumour growth was inhibited after treatment with taxol‐doxorubicin, demonstrating increased drug sensitivity. This study suggests that pre‐treatment with miR‐495 before chemotherapy could improve the curative effect on MDR1‐based MDR cancer.

Metal-organic frameworks (MOFs) have attracted tremendous attention for several novel applications. However, functional MOFs with light-responsive circularly polarized luminescence (CPL) are not examined in detail. Therefore, a dual CPL switch exhibiting both upconversion (UC) and downshifting (DS) CPL in the solid state is constructed by loading a luminescent diarylethene derivative (DAEC) and UC nanoparticles (UCNPs) into chiral MOFs. The chiral MOF⊃DAEC composites exhibit both photoswitchable luminescence and DS-CPL properties under alternating UV and visible light irradiation. Additionally, a reversible UC-CPL switch is realized using near-infrared (NIR) and visible light irradiation by introducing energy-level-matched UCNPs and DAEC into the chiral MOFs. The dissymmetry factor (glum ) of UC-CPL is noted to be significantly amplified through energy transfer compared to that of DS-CPL, which indicates that the information on circular polarization can be manipulated by altering the incident light. A chiroptical logic circuit with a 2D information output is designed with UV, visible, and NIR light as inputs by setting a rational threshold.

Purpose Deformable multimodal image registration, which can benefit radiotherapy and image guided surgery by providing complementary information, remains a challenging task in the medical image analysis field due to the difficulty of defining a proper similarity measure. This article presents a novel, robust and fast binary descriptor, the discriminative local derivative pattern (dLDP), which is able to encode images of different modalities into similar image representations. Methods dLDP calculates a binary string for each voxel according to the pattern of intensity derivatives in its neighborhood. The descriptor similarity is evaluated using the Hamming distance, which can be efficiently computed, instead of conventional L1 or L2 norms. For the first time, we validated the effectiveness and feasibility of the local derivative pattern for multimodal deformable image registration with several multi-modal registration applications. Results dLDP was compared with three state-of-the-art methods in artificial image and clinical settings. In the experiments of deformable registration between different magnetic resonance imaging (MRI) modalities from BrainWeb, between computed tomography and MRI images from patient data, and between MRI and ultrasound images from BITE database, we show our method outperforms localized mutual information and entropy images in terms of both accuracy and time efficiency. We have further validated dLDP for the deformable registration of preoperative MRI and three-dimensional intraoperative ultrasound images. Our results indicate that dLDP reduces the average mean target registration error from 4.12 mm to 2.30 mm. This accuracy is statistically equivalent to the accuracy of the state-of-the-art methods in the study; however, in terms of computational complexity, our method significantly outperforms other methods and is even comparable to the sum of the absolute difference. Conclusions The results reveal that dLDP can achieve superior performance regarding both accuracy and time efficiency in general multimodal image registration. In addition, dLDP also indicates the potential for clinical ultrasound guided intervention.

Gremlin is a bone morphogenic protein (BMP) antagonist and is elevated in diabetic kidney tissues. In the early course of diabetic nephropathy (DN), podocyte are injured. We studied the protein and gene expression of gremlin in mice podocytes cultured in hyperglycemia ambient. The role of gremlin on podocyte injury and the likely signaling pathways involved were determined. Expression of gremlin was visualized by confocal microscopy. Recombinant mouse gremlin and small interfering RNA (siRNA) targeting to gremlin1 identified the role played by gremlin on podocytes. Study of canonical (smad2/3) and non-canonical (p38MAPK and JNK1/2) transforming growth factor beta (TGFβ)/smad mediated signaling revealed the putative signaling mechanisms involved. Smad2/3 siRNA and TGFβ receptor inhibition (SB431542) were used to probe canonical TGFβ/smad signaling in gremlin-induced podocyte injury. Apoptosis of podocytes was measured by TUNEL assay. Gremlin expression was enhanced in high glucose cultured mouse podocytes, and was localized predominantly in the cytoplasm and negligibly on the cell membrane. Not only expression of nephrin and synaptopodin were decreased on treatment with gremlin, but also synaptopodin rearrangement and nephrin relocalization were evident. Knockdown gremlin1 or smad2/3 by siRNA, and inhibition of TGFβR (SB431542) attenuated podocyte injury. Inhibition of canonical TGF-β signal blocked the injury of gremlin on podocytes. In conclusion, gremlin was clearly elevated in high glucose cultured mouse podocytes, and likely employed endogenous canonical TGFβ1/Smad signaling to induce podocyte injury. Knockdown gremlin1 by siRNA may be clinically useful in the attenuation of podocyte injury.

Purpose: In adaptive radiation therapy of prostate cancer, fast and accurate registration between the planning image and treatment images of the patient is of essential importance. With the authors' recently developed deformable surface model, prostate boundaries in each treatment image can be rapidly segmented and their correspondences (or relative deformations) to the prostate boundaries in the planning image are also established automatically. However, the dense correspondences on the nonboundary regions, which are important especially for transforming the treatment plan designed in the planning image space to each treatment image space, are remained unresolved. This paper presents a novel approach to learn the statistical correlation between deformations of prostate boundary and nonboundary regions, for rapidly estimating deformations of the nonboundary regions when given the deformations of the prostate boundary at a new treatment image. Methods: The main contributions of the proposed method lie in the following aspects. First, the statistical deformation correlation will be learned from both current patient and other training patients, and further updated adaptively during the radiotherapy. Specifically, in the initial treatment stage when the number of treatment images collected from the current patient is small, the statistical deformation correlation is mainly learned from other training patients. Asmore » more treatment images are collected from the current patient, the patient-specific information will play a more important role in learning patient-specific statistical deformation correlation to effectively reflect prostate deformation of the current patient during the treatment. Eventually, only the patient-specific statistical deformation correlation is used to estimate dense correspondences when a sufficient number of treatment images have been acquired from the current patient. Second, the statistical deformation correlation will be learned by using a multiple linear regression (MLR) model, i.e., ridge regression (RR) model, which has the best prediction accuracy than other MLR models such as canonical correlation analysis (CCA) and principal component regression (PCR). Results: To demonstrate the performance of the proposed method, we first evaluate its registration accuracy by comparing the deformation field predicted by our method with the deformation field estimated by the thin plate spline (TPS) based correspondence interpolation method on 306 serial prostate CT images of 24 patients. The average predictive error on the voxels around 5 mm of prostate boundary is 0.38 mm for our method of RR-based correlation model. Also, the corresponding maximum error is 2.89 mm. We then compare the speed for deformation interpolation by different methods. When considering the larger region of interest (ROI) with the size of 512 x 512 x 61, our method takes 24.41 seconds to interpolate the dense deformation field while TPS method needs 6.7 minutes; when considering a small ROI (surrounding prostate) with size of 112 x 110 x 93, our method takes 1.80 seconds, while TPS method needs 25 seconds. Conclusions: Experimental results show that the proposed method can achieve much faster registration speed yet with comparable registration accuracy, compared to the TPS-based correspondence (or deformation) interpolation approach.« less

Janus kinase (JAK) signal transducers, and activators of transcription (STAT), contribute to diabetic nephropathy. Here we show that one of the suppressors of cytokine signaling (SOCS) proteins, SOCS-1, was upregulated in human mesangial cells (HMCs) under high glucose conditions, along with the activation of JAK2, STAT1, and STAT3. Overexpression of SOCS-1 in HMCs inhibited HG-induced JAK2/STAT activation, c-Fos/c-Jun expression, and increased synthesis of TGF-β1 and fibronectin. These data suggest that SOCS-1 inhibits HG-induced overexpression of TGF-β1 and synthesis of fibronectin in HMC, which may be via JAK/STAT pathway.

Weak immunogenicity of chronic lymphocytic leukaemia (CLL) cells may contribute to disease progression and inhibit the effectiveness of immunotherapies, such as vaccines. Agents that can enhance the antigen presenting capabilities of CLL cells might then help to improve the clinical results of immunotherapies. This study investigated the effects of the common gamma chain-binding cytokines, interleukin (IL)-2 and IL-15, on costimulatory properties of primary CLL cells from 51 patients. IL-2 improved the ability of CLL cells to stimulate T cell proliferation and increased the expression of costimulatory molecules (particularly CD80) in a dose-dependent fashion, especially in CLL cells with weak expression of CD38. CD80 and CD86 induction by IL-2 were positively regulated through the mitogen-activated protein kinase pathway, while CD86 expression was negatively regulated through Janus kinase pathways. However, further activation with protein kinase C agonists was required for IL-2 activated CLL cells to stimulate autologous T cells sufficiently to clear bystander CLL cells from mixed lymphocyte responses. IL-15 had similar effects on the costimulatory properties of CLL cells. These results suggest a role for IL-2, or IL-15, in immunotherapeutic strategies for CLL.

Perovskite nanocrystals are attracting great interest due to their excellent photonic properties. Here, through a supramolecular self-assembly approach, the perovskite nanocrystals (NCs) with a novel circularly polarized luminescence (CPL) are successfully endowed. It is found that the achiral perovskite NCs can coassemble with chiral gelator in nonpolar solvents, in which the gelator molecules modify the surface of the perovskite NCs. Through such cogelation, the molecular chirality can transfer to the NCs resulting in CPL signals with a dissymmetric factor (glum ) up to 10-3 . Furthermore, depending on the molecular chirality of the gelator, the CPL sense can be selected and the mirror-imaged CPL is obtained. Such gels can be further embedded into the polymer film to facilitate flexible CPL devices. It is envisaged that this approach will afford a new insight into the designing of the functional chiroptical materials.