Leptin overexpression is closely correlated with gastric cancer (GC) invasion, but its exact effect and the underlying mechanism in tumorigenesis remain poorly understood. Membrane type 1-matrix metalloproteinase (MT1-MMP), a surface-anchored 'master switch' proteinase, is overexpressed and plays crucial roles in tumor invasion. Here, we characterized the influence of leptin on the generation and surface localization of MT1-MMP in GC and elucidated its molecular mechanisms. Our results revealed that leptin promoted GC cell invasion in vitro by upregulating MT1-MMP expression. Furthermore, cell surface biotinylation assay and flow cytometry demonstrated that the surface expression of MT1-MMP was also enhanced by leptin, and knockdown of kinesin family member 1B (KIF1B, a microtubule plus end-directed monomeric motor protein) by small interference RNA inhibited this process. Notably, coimmunoprecipitation analysis indicated that leptin enhanced the interaction of MT1-MMP with KIF1B in a time-dependent manner, which consequently contributed to GC cell invasion. Moreover, leptin increased MT1-MMP or KIF1B expression by the protein kinase B (AKT) pathway and extracellular signal-regulated kinase 1/2 partially participated in this process. However, only AKT was implicated in the leptin-mediated membrane localization of MT1-MMP. Immunohistochemistry analysis revealed that leptin, MT1-MMP and KIF1B are overexpressed in GC tissues, and they positively correlated with clinical stage and lymph node metastasis. These observations indicate that this regulatory network exists in vivo. Taken together, our findings suggest that leptin is an effective intracellular stimulator of MT1-MMP and that leptin-enhanced cell surface localization of MT1-MMP is dependent on KIF1B, which consequently plays a critical role in GC invasion.

BackgroundChemokines have been recognized as important modulators of angiogenesis, and they play critical roles in the development and metastasis of hepatocellular carcinoma (HCC), although their origins and latent molecular mechanisms remain elusive. The aim of this study was to investigate how activated hepatic stellate cells (a-HSCs) promote angiogenesis in HCC.MethodsA total of 22 HCC patients were enrolled randomly. We used immunohistochemistry, western blotting, and enzyme-linked immunosorbent assay (ELISA) to analyse the production of interleukin-8 (IL-8) in a-HSCs derived from HCC tissues. The angiogenic effects of IL-8 in vitro and in vivo were assessed by ELISA, real-time quantitative polymerase chain reaction, capillary tube formation assay, and chick embryo chorioallantoic membrane assay.ResultsThe present study showed that IL-8 was enriched predominantly in the tumour stroma of HCC tissues and was mainly derived from a-HSCs, rather than from hepatoma cells, in vivo and in vitro. Angiogenesis was most active at the invading edge, which was close to the a-HSCs. The angiogenic effect was dramatically attenuated by an IL-8 neutralizing antibody both in vitro and in vivo. Moreover, the IL-8 neutralizing antibody down-regulated Ser727-phosphorylated STAT3 levels in hepatoma cells treated with a-HSCs conditioned medium.ConclusionsThese findings reveal that a-HSCs within the stroma of HCC contribute to tumour angiogenesis via IL-8.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0730-7) contains supplementary material, which is available to authorized users.

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Exploring significant ultraviolet/deep‐ultraviolet nonlinear optical (NLO) materials is hindered by rigorous and contradictory requirements, especially, possessing a moderate optical birefringence to meet phase‐matching (PM). Except for suitable birefringence, small chromatic dispersion is also crucial to blue‐shift the PM wavelength. Here, the introduction of a fluorinated tetrahedral boron‐centred chromophore strategy was proposed to optimize the chromatic dispersion. Herein, the [BF4]− unit with a large HOMO–LUMO band gap was introduced to the Na−B−O−F system and Na4B8O9F10 was designed and synthesized successfully for the first time. Na4B8O9F10 with an optimized chromatic dispersion can achieve a short second harmonic generation PM wavelength of 240 nm with a relatively small birefringence (0.036@1064 nm). Notably, Na4B8O9F10 is the first acentric crystal with [BF4]− units among the reported metal–fluorooxoborate systems, involving isolated [BF4]− and novel [B7O10F6]5− fundamental building blocks.

PURPOSE: To investigate the accuracy of intraocular lens (IOL) power calculation formulas using swept-source optical coherence tomography (SS-OCT). METHODS: Eyes with biometry measurement by IOLMaster 700 (Carl Zeiss Meditec AG), uncomplicated phacoemulsification, and IOL implantation were enrolled in this retrospective study. Newly released artificial intelligence–based formulas including Hill-Radial Basis Function (RBF) 2.0, Kane, and PEARL-DGS were compared with Gaussian optics-based standard formulas. The refraction predicted by each formula was compared with the actual refractive outcome in spherical equivalent. RESULTS: A total of 410 eyes of 410 patients were included in this study. Using optimized constants for SS-OCT biometry led to a significant decrease in median absolute error (MedAE) for Barrett, Haigis, and Hoffer Q formulas compared with using User Group for Laser Interference Biometry constants ( P < .05). Overall, Olsen (0.283 diopters [D]) and Kane (0.286 D) formulas had significantly lower MedAEs than RBF 2.0 (0.314 D), Haigis (0.322 D), SRK/T (0.371 D), Holladay 1 (0.376 D), and Hoffer Q (0.379 D) formulas under constant optimization ( P < .05). The first four formulas with the lowest standard deviations of prediction error were Kane (0.451 D), Olsen (0.456 D), EVO 2.0 (0.460 D), and Barrett (0.470 D). Olsen (47.1%), Barrett (45.9%), Kane (45.4%), and EVO 2.0 (45.1%) formulas had greater proportions of eyes within ±0.25 D of the predicted refraction than Hoffer Q (35.9%), SRK/T (35.9%), and Holladay 1 (33.4%) formulas ( P < .05). CONCLUSIONS: Constant optimization for SS-OCT biometry further improves the performance of formulas. The most accurate prediction of postoperative refraction can be achieved with Barrett, EVO 2.0, Kane, and Olsen formulas. [ J Refract Surg . 2020;36(7):466–472.]

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The overexpression of leptin is a crucial feature for the maintenance of pregnancy. The effects of leptin on trophoblast invasion are important to its reproductive function, but the underlying mechanisms remain poorly understood. MMP14 is a member of matrix metalloproteinase (MMP) family that is closely involved in the invasion process. Here, we characterized the importance of MMP14 in the proinvasion effect of leptin on EVT cells and elucidated its molecular mechanisms. Transwell assay revealed that leptin promoted invasion of the immortalized EVT cell line HTR-8/SVneo in a dose- and time-related fashion. Further studies suggested that leptin enhanced HTR-8/SVneo cell invasion by up-regulating MMP14 expression and that knockdown of MMP14 by small interference RNA (siRNA) blocked the proinvasion effect of leptin. Notably, leptin promoted the expression of Notch1 receptor and activated its signaling in HTR-8/SVneo cells, and blocking this pathway by siRNA inhibited both leptin-enhanced MMP14 expression and invasiveness of HTR-8/SVneo cells. Such effects of Notch1 signaling were related with the activation of the PI3K/Akt pathway, which was significantly activated after leptin stimulation and was interfered by Notch1 signaling perturbation. Taken together, our observations suggest that leptin is an effective regulator of MMP14 expression, which consequently plays critical roles in invasion of EVT cells. The promoting effects of leptin on MMP14 require the cross talk between Notch1 and PI3K/Akt signaling pathways.

Background Loss-of-function mutations in the CLCN2 gene were recently discovered to be a cause of a type of leukodystrophy named CLCN2 -related leukoencephalopathy (CC2L), which is characterized by intramyelinic edema. Herein, we report a novel mutation in CLCN2 in an individual with leukodystrophy. Case presentation A 38-year-old woman presented with mild hand tremor, scanning speech, nystagmus, cerebellar ataxia in the upper limbs, memory decline, tinnitus, and dizziness. An ophthalmologic examination indicated macular atrophy, pigment epithelium atrophy and choroidal capillary atrophy. Brain magnetic resonance imaging (MRI) showed the diffuse white matter involvement of specific white matter tracts. Decreased diffusion anisotropy was detected in various brain regions of the patient. Diffusion tensor tractography (DTT) showed obviously thinner tracts of interest than in the controls, with a decreased fiber number (FN), increased radial diffusivity (RD) and unchanged axial diffusivity (AD). A novel homozygous c.2257C > T (p.Arg753Ter) mutation in exon 20 of the CLCN2 gene was identified. Conclusion CC2L is a rare condition characterized by diffuse edema involving specific fiber tracts that pass through the brainstem. The distinct MRI patterns could be a strong indication for CLCN2 gene analysis. The findings of our study may facilitate the understanding of the pathophysiology and clinical symptoms of this disease. Electronic supplementary material The online version of this article (10.1186/s12883-019-1390-7) contains supplementary material, which is available to authorized users.