Rationale: Vitamin D (VD) has been suggested to have antitumor effects, however, research on the role of its transporter vitamin D-binding protein (VDBP, gene name as GC) in tumors is limited. In this study, we demonstrated the mechanism underlying the inhibition of vasculogenic mimicry (VM) by VDBP in hepatocellular carcinoma (HCC) and proposed an anti-tumor strategy of combining anti-PD-1 therapy with VD. Methods: Three-dimensional cell culture models and mice with hepatocyte-specific GC deletion were utilized to study the correlation between VDBP expression and VM. A patient-derived tumor xenograft (PDX) model was further applied to validate the therapeutic efficacy of VD in combination with an anti-PD-1 drug. Results: The study revealed that VDBP expression is negatively correlated with VM in HCC patients and elevated VDBP expression is associated with a favorable prognosis. The mechanism studies suggested VDBP hindered the binding of Twist1 on the promoter of VE-cadherin by interacting with its helix-loop-helix DNA binding domain, ultimately leading to the inhibition of VM. Furthermore, VD facilitated the translocation of the vitamin D receptor (VDR) into the nucleus where VDR interacts with Yin Yang 1 (YY1), leading to the transcriptional activation of VDBP. We further demonstrated that the combination of VD and anti-PD-1 led to an improvement in the anti-tumor efficacy of an anti-PD-1 drug. Conclusion: Collectively, we identified VDBP as an important prognostic biomarker in HCC patients and uncovered it as a therapeutic target for enhancing the efficacy of immune therapy.

UNASSIGNED: To evaluate the safety and outcome of image-guided sclerotherapy for treating venous malformations (VMs) of the face.
UNASSIGNED: A multicenter cohort of 68 patients with VMs primarily affecting the face was retrospectively investigated. In total, 142 image-guided sclerotherapies were performed using gelified ethanol and/or polidocanol. Clinical and imaging findings were assessed to evaluate clinical response, lesion size reduction, and complication rates. Sub-analyses of complication rates depending on type and injected volume of the sclerosant as well as of pediatric versus adult patient groups were conducted.
UNASSIGNED: Mean number of procedures per patient was 2.1 (±1.7) and mean follow-up consisted of 8.7 months (±6.8 months). Clinical response (n = 58) revealed a partial relief of symptoms in 70.7% (41/58), 13/58 patients (22.4%) presented symptom-free while only 4/58 patients (6.9%) reported no improvement. Post-treatment imaging (n = 52) revealed an overall objective response rate of 86.5% (45/52). The total complication rate was 10.6% (15/142) including 4.2% (7/142) major complications, mostly (14/15, 93.3%) resolved by conservative means. In one case, a mild facial palsy persisted over time. The complication rate in the gelified ethanol subgroup was significantly higher compared to polidocanol and to the combination of both sclerosants (23.5 vs. 6.0 vs. 8.3%, p = 0.01). No significant differences in complications between the pediatric and the adult subgroup were observed (12.1 vs. 9.2%, p = 0.57). Clinical response did not correlate with lesion size reduction on magnetic resonance imaging (MRI).
UNASSIGNED: Image-guided sclerotherapy is effective for treating VMs of the face. Clinical response is not necessarily associated with size reduction on imaging. Despite the complex anatomy of this location, the procedures are safe for both adults and children.

Bioelectricity is defined as endogenous electrical signaling mediated by the dynamic distribution of charged molecules. Recently, increasing evidence has revealed that cellular bioelectric signaling is critical for regulating embryonic development, regeneration, and congenital diseases. However, systematic real-time in vivo dynamic electrical activity monitoring of whole organisms has been limited, mainly due to the lack of a suitable model system and voltage measurement tools for in vivo biology. Here, we addressed this gap by utilizing a genetically stable zebrafish line, Tg (ubiquitin: ASAP1), and ASAP1 (Accelerated sensor of action potentials 1), a genetically encoded voltage indicator (GEVI). With light-sheet microscopy, we systematically investigated cell membrane potential (Vm) signals during different embryonic stages. We found cells of zebrafish embryos showed local membrane hyperpolarization at the cleavage furrows during the cleavage period of embryogenesis. This signal appeared before cytokinesis and fluctuated as it progressed. In contrast, whole-cell transient hyperpolarization was observed during the blastula and gastrula stages. These signals were generally limited to the superficial blastomere, but they could be detected within the deeper cells during the gastrulation period. Moreover, the zebrafish embryos exhibit tissue-level cell Vm signals during the segmentation period. Middle-aged somites had strong and dynamic Vm fluctuations starting at about the 12-somite stage. These embryonic stage-specific characteristic cellular bioelectric signals suggest that they might play a diverse role in zebrafish embryogenesis that could underlie human congenital diseases.

Studies have shown that inhibition of PI3K/AKT signaling is a key strategy for the treatment of tyrosine kinase inhibitor resistance in non-small cell lung cancer (NSCLC). Vasculogenic mimicry (VM) not only accelerates tumor progression but also increases drug-induced resistance. As a tumor suppressor, protein phosphatase 2A (PP2A) is a ubiquitous conserved serine/threonine phosphatase. While its effects and mechanisms on VM formation and invasion in NSCLC remain unclear. The present study aimed to investigate the role of PP2A in VM formation and elucidate the underlying mechanisms. Results showed that PP2A could significantly inhibit VM formation and VM-dependent behavior, including invasion and migration both in vitro and in vivo. Activation of PP2A with FTY720 or Ad-PP2A reduced phosphorylated AKT and inhibited ZEB1 transcription, thereby further downregulating the expression of MMP-2, VE-cadherin, and VEGFR-2, whereas inhibition of PP2A with okadaic acid (OA) or Ad-dn-PP2A exerted the opposite effect. Furthermore, PP2A inhibited tumor growth and VM formation in the xenograft tumor model. PI3K inhibitor BENC-511 could potentiate activation of PP2A, leading to inhibition of p-AKT/ZEB1 and VM formation in vitro and in vivo. This study indicated that PP2A could regulate VM formation in NSCLC through the PI3K/AKT/ZEB1 axis. PP2A reactivation or combination with PI3K inhibitor might be a more effective treatment against advanced NSCLC by inhibiting VM formation.

Treating breast cancer, especially in the invasive state, is one of the challenges in treating cancer. Invasion and metastasis are factors in the failure of breast cancer treatments. One of the causes of this failure is the formation of new blood vessels to nourish the tumor cells. Although many drugs target the formation of blood vessels, the therapeutic results, especially in breast cancer, have not been very successful and even recurrence of the disease has been observed. Therefore, it can be concluded that other mechanisms are involved in feeding and delivering oxygen to tumor cells, the most important of which is the vascular mimicry (VM). The ability of cancer cells to organize themselves into vascular-like structures for the obtain of nutrients and oxygen independently of normal blood vessels or angiogenesis named Vasculogenic mimicry. In this review article, we tried to review the formation VM and the therapeutic potential of targeting VM formation in the treatment of breast cancer.

Beyond traditional endothelium-dependent vessel (EDV), vascular mimicry (VM) is another critical tumor angiogenesis that further forms in many malignant metastatic tumors. However, the existing anti-angiogenesis combined chemotherapeutics strategies are only efficient for the treatment of EDV-based subcutaneous tumors, but remain a great challenge for the treatment of in situ malignant metastatic tumor associated with EDV and VM. Here, we demonstrate a self-assembled nanoparticle (VE-DDP-Pro) featuring self-anti-EDV and -VM capacity enables to significantly enhance the treatment efficacy of cisplatin (DDP) against the growth and metastasis of ovarian cancer. The VE-DDP-Pro is constructed by patching DDP loaded cRGD-folate-heparin nanoparticles (VE) onto the surface of protamine (Pro) nanoparticle. We demonstrated the self-anti-angiogenesis capacity of VE-DDP-Pro was attributed to VE, which could significantly inhibit the formation of EDV and VM by regulating signaling pathway of MMP-2/VEGF, AKT/mTOR/MMP-2/Laminin and AKT/mTOR/EMT, facilitating chemotherapeutics to effectively suppress the development and metastasis of ovarian cancer. Thus, combing with the chemotherapeutics effectiveness of DDP, the VE-DDP-Pro can significantly enhance treatment efficacy and prolong median survival of mice with metastatic ovarian cancer. We believe our self-assembled nanoparticles integrating the anti-EDV and anti-VM capacity provide a new preclinical sight to enhance the efficacy of chemotherapeutics for the treatment malignant metastasis tumor.

Hypoxic microenvironment represents the hallmark of solid tumors including colorectal cancer (CRC) and facilitates angiogenesis and chemoresistance, leading to poor prognosis. lncRNA NORAD acts as an oncogenic gene to orchestrate cancer progression by regulating cell proliferation and migration. Notably, an emerging study corroborates the elevation of NORAD during hypoxic conditions in pancreatic cancer. Nevertheless, its biological role in hypoxia-evoked CRC remains unclear. Herein, enhanced expression of NORAD and hypoxia-inducible factor-1α (HIF-1α) was validated in CRC tissues. Furthermore, there was a positive association between NORAD and HIF-1α in CRC tissues. CRC cells exposed to hypoxia exhibited a stronger ability to form vasculogenic mimicry (VM) and resistance to 5-fluorouracil (5-FU), concomitant with higher expression of NORAD. NORAD knockdown restrained hypoxia-induced VM formation and VM marker VE-cadherin expression. Moreover, knockdown of NORAD counteracted CRC cell resistance to 5-FU by decreasing cell viability and increasing cell apoptosis. Additionally, NORAD loss reduced hypoxia-induced HIF-1α expression and subsequent epithelial-mesenchymal transition (EMT) by increasing E-cadherin and inhibiting N-cadherin expression. Intriguingly, HIF-1α overexpression reversed NORAD downregulation-mediated inhibition of VM formation and 5-FU resistance. There was a low expression of miR-495-3p in CRC tissues. Furthermore, NORAD could act as a competitive endogenous RNA of miR-495-3p to regulate HIF-1α. Importantly, inhibition of miR-495-3p muted the efficacy of NORAD loss in hypoxia-induced EMT, VM, and chemoresistance. Thus, the current data highlight that NORAD knockdown may antagonize hypoxia-triggered CRC malignancy by suppressing VM formation and chemoresistance by sponging miR-495-3p/HIF-1α to regulate EMT, supporting a promising therapeutic target for refractory hypoxia in CRC.

Introduction: Sleep disorders can affect the overall health and quality of life of patients. This study was conducted to compare the differences of sleep disorders in vestibular migraine (VM) patients and benign paroxysmal positional vertigo (BPPV) patients. Methods: VM patients, BPPV patients, and healthy controls (HCs) were recruited. Pittsburgh sleep quality index and polysomnography monitoring were used as subjective and objective, respectively, evaluation methods to evaluate the sleep quality of participants in the latest month. Results: Fifty-seven BPPV patients, 48 VM patients, and 42 HCs were included in this study. There were 79.16% VM patients, 54.39% BPPV patients, and 14.28% HCs with sleep disorders. The difference in the incidence rate of sleep disorders was significant between VM patients and BPPV patients (p = 0.008) and significantly higher in both the VM group (p < 0.00001) and BPPV group (p = 0.00004) than in the HC groups (14.28%). Compared with BPPV patients, the VM patients had the significantly lower sleep efficiency (p < 0.001) and N3 (p < 0.001) and the significantly higher time of wake-up after sleep onset (p < 0.001), N1 (p < 0.001), and N2 (p < 0.001). Meanwhile, the VM patients had significantly higher incidence rates of severe obstructive sleep apnea hypoventilation syndrome (p = 0.001) and periodic leg movement in sleep (p = 0.016). Conclusion: The incidence rate of sleep disorders was significantly higher in both VM and BPPV patients than in the HC groups. To improve the curative effects, clinicians should pay more attention to the comorbidity of sleep disorders in treating VM and BPPV.

Cloud computing is new technology that has considerably changed human life at different aspect over the last decade. Especially after the COVID-19 pandemic, almost all life activity shifted into cloud base. Cloud computing is a utility where different hardware and software resources are accessed on pay per user ground base. Most of these resources are available in virtualized form and virtual machine (VM) is one of the main elements of visualization.VM used in data center for distribution of resource and application according to benefactor demand. Cloud data center faces different issue in respect of performance and efficiency for improvement of these issues different approaches are used. Virtual machine play important role for improvement of data center performance therefore different approach are used for improvement of virtual machine efficiency (i-e) load balancing of resource and task. For the improvement of this section different parameter of VM improve like makespan, quality of service, energy, data accuracy and network utilization. Improvement of different parameter in VM directly improve the performance of cloud computing. Therefore, we conducting this review paper that we can discuss about various improvements that took place in VM from 2015 to 20,201. This review paper also contain information about various parameter of cloud computing and final section of paper present the role of machine learning algorithm in VM as well load balancing approach along with the future direction of VM in cloud data center.

Long non-coding RNA (lncRNA) HULC (highly upregulated in liver cancer) is considered as an oncogenic factor for various malignant tumors. This study aimed to reveal the role of lncRNA HULC in the malignant behavior of glioblastoma (GBM) by exploring its effects on the epithelial-mesenchymal transition (EMT) and vasculogenic mimicry (VM) of human GBM.
The contents of VM in 27 GBM samples were assessed by immunohistochemistry-histology and their association with progress-free survival (PFS) was analyzed. Human GBM SHG44 and U87 cells were manipulated to establish stable lncRNA HULC overexpressing and silencing cells by lentivirus-based technology. The effects of altered lncRNA HULC on vasculogenic tubular formation, invasion, and EMT process in GBM cells were tested in vitro and the growth of implanted GBM tumors and their EMT process were examined in vivo.
The numbers of VM were positively associated with disease progression, but negatively with PFS periods of GBM patients. Compared with the control vec cells, lncRNA HULC overexpression significantly increased the tubular formation, invasion, and EMT process of both SHG44 and U87 cells, accompanied by promoting the growth of implanted GBM tumors and EMT process in mice. LncRNA HULC silencing had opposite effects on the tubular formation, invasion, and EMT process as well as tumor growth of GBM cells.
LncRNA HULC stimulates the EMT process and VM in human GBM, and may be a therapeutic target for intervention of GBM.