Near-infrared II fluorescence-guided glioblastoma surgery targeting monocarboxylate transporter 4 combined with photothermal therapy.

BACKGROUND: Surgery is crucial for glioma treatment, but achieving complete tumour removal remains challenging. We evaluated the effectiveness of a probe targeting monocarboxylate transporter 4 (MCT4) in recognising gliomas, and of near-infrared window II (NIR-II) fluorescent molecular imaging and photothermal therapy as treatment strategies. METHODS: We combined an MCT4-specific monoclonal antibody with indocyanine green to create the probe. An orthotopic mouse model and a transwell model were used to evaluate its ability to guide tumour resection using NIR-II fluorescence and to penetrate the blood-brain barrier (BBB), respectively. A subcutaneous tumour model was established to confirm photothermal therapy efficacy. Probe specificity was assessed in brain tissue from mice and humans. Finally, probe effectiveness in photothermal therapy was investigated. FINDINGS: MCT4 was differentially expressed in tumour and normal brain tissue. The designed probe exhibited precise tumour targeting. Tumour imaging was precise, with a signal-to-background (SBR) ratio of 2.8. Residual tumour cells were absent from brain tissue postoperatively (SBR: 6.3). The probe exhibited robust penetration of the BBB. Moreover, the probe increased the tumour temperature to 50 °C within 5 min of laser excitation. Photothermal therapy significantly reduced tumour volume and extended survival time in mice without damage to vital organs. INTERPRETATION: These findings highlight the potential efficacy of our probe for fluorescence-guided surgery and therapeutic interventions. FUNDING: Jilin Province Department of Science and Technology (20200403079SF), Department of Finance (2021SCZ06) and Development and Reform Commission (20200601002JC); National Natural Science Foundation of China (92059207, 92359301, 62027901, 81930053, 81227901, U21A20386); and CAS Youth Interdisciplinary Team (JCTD-2021-08).

RELN gene-related drug-resistant epilepsy with periventricular nodular heterotopia treated with radiofrequency thermocoagulation: a case report.

An increasing number of gene mutations associated with epilepsy have been identified, some linked to gray matter heterotopia-a common cause of drug-resistant epilepsy. Current research suggests that gene mutation-associated epilepsy should not be considered a contraindication for surgery in epilepsy patients. At present, stereoelectroencephalography-guided radiofrequency thermocoagulation is an important method to treat periventricular nodular heterotopia-associated drug-resistant epilepsy. We present a case of drug-resistant epilepsy, accompanied by periventricular nodular heterotopia and a heterozygous mutation of the RELN gene, successfully treated with radiofrequency thermocoagulation, resulting in a favorable outcome.

A scientometric analysis of immunotherapies for gliomas: Focus on GBM.

Gliomas are the most prevalent primary malignant brain tumors worldwide, with glioblastoma (GBM) being the most common and aggressive type. The standard therapy for GBM has remained unchanged for nearly two decades, with no significant improvement in survival outcomes. Despite several barriers such as the tumor microenvironment (TME) and blood-brain barrier, immunotherapies bring new hope for the treatment of GBM. To better understand the development and progress of immunotherapies in GBM, we made this scientometric analysis of this field. A total of 3753 documents were obtained from the Web of Science Core Collection, with publication years ranging from 1999 to 2022. The Web of Science platform, CiteSpace, and VOS viewer were used to conduct the scientometric analysis. The results of scientometric analysis showed that this field has recently become a popular topic of interest. The United States had the most publications among 89 countries or regions. Keyword analysis indicated significant areas in the field of immunotherapies for GBM, especially TME, immune checkpoint blockades (ICBs), chimeric antigen receptor T (CAR-T) cells, vaccines, and oncolytic viruses (OVs). Overall, we hope that this scientometric analysis can provide insights for researchers and promote the development of this field.

Mechanism of HDAC1 Regulating Iron Overload-Induced Neuronal Oxidative Damage After Cerebral Hemorrhage.

Iron overload is associated with brain edema in the context of intracerebral hemorrhage (ICH). Here, we investigated the role of histone deacetylase 1 (HDAC1) in mediating oxidative damage induced by iron overload after ICH. Utilizing ICH mouse models and FeCl2-induced HT-22 cell models, we assessed HDAC1 expression and its impact on iron overload and oxidative damage. We examined the levels of Kruppel like factor 4 (KLF4), RAN binding protein 9 (RANBP9), as well as the acetylation levels of HDAC1 and histones H3 and H4 in the KLF4 promoter, and the KLF4 level in the RANBP9 promoter. Additionally, we investigated the binding relationships between KLF4 and the RANBP9 promoter, HDAC1 and miR-129-5p. Our results demonstrated elevated HDAC1 expression in ICH mice and FeCl2-induced HT-22 cells. HDAC1 silencing improved neurological function in mice, reduced brain edema, and alleviated iron overload and oxidative damage in vitro. HDAC1 downregulated KLF4 expression by reducing acetylation levels in the KLF4 promoter, leading to decreased KLF4 enrichment in the RANBP9 promoter and increased RANBP9 expression. Furthermore, upstream miR-129-5p inhibited HDAC1, and the downregulation of miR-129-5p mitigated the protective effect of HDAC1 silencing. Collectively, our findings highlight the significant role of HDAC1 in exacerbating iron overload-induced oxidative damage following ICH and its regulation by miR-129-5p.

A Flexible and Stretchable MXene/Waterborne Polyurethane Composite-Coated Fiber Strain Sensor for Wearable Motion and Healthcare Monitoring.

Fiber-based flexible sensors have promising application potential in human motion and healthcare monitoring, owing to their merits of being lightweight, flexible, and easy to process. Now, high-performance elastic fiber-based strain sensors with high sensitivity, a large working range, and excellent durability are in great demand. Herein, we have easily and quickly prepared a highly sensitive and durable fiber-based strain sensor by dip coating a highly stretchable polyurethane (PU) elastic fiber in an MXene/waterborne polyurethane (WPU) dispersion solution. Benefiting from the electrostatic repulsion force between the negatively charged WPU and MXene sheets in the mixed solution, very homogeneous and stable MXene/WPU dispersion was successfully obtained, and the interconnected conducting networks were correspondingly formed in a coated MXene/WPU shell layer, which makes the as-prepared strain sensor exhibit a gauge factor of over 960, a large sensing range of over 90%, and a detection limit as low as 0.5% strain. As elastic fiber and mixed solution have the same polymer constitute, and tight bonding of the MXene/WPU conductive composite on PU fibers was achieved, enabling the as-prepared strain sensor to endure over 2500 stretching-releasing cycles and thus show good durability. Full-scale human motion detection was also performed by the strain sensor, and a body posture monitoring, analysis, and correction prototype system were developed via embedding the fiber-based strain sensors into sweaters, strongly indicating great application prospects in exercise, sports, and healthcare.

Taxifolin inhibits melanoma proliferation/migration impeding USP18/Rac1/JNK/ß-catenin oncogenic signaling.

BACKGROUND: Metastatic melanoma is a fatal cancer. Despite the advances in targeted therapy and immunotherapy for patients with melanoma, drug resistance and low response rates pose a considerable challenge. Taxifolin is a multifunctional natural compound with emerging antitumor potentials. However, its utility in melanoma treatment remains unclear. PURPOSE: The study aimed to investigate the effect of purified Taxifolin from Larix olgensis roots (Changbai Mountain, China) on melanoma and explore the underlying mechanism. METHODS: Purified Taxifolin from Larix olgensis roots was evaluated for its antimelanoma effects in vitro and in vivo settings. RNA-seq analysis was performed to explore the underlying mechanism. RESULTS: Purified Taxifolin (> 99 %) from Larix olgensis roots inhibited the proliferation and migration of B16F10 melanoma cells at 200 and 400 µM, and of A375 cells at 100 and 200 µM. Taxifolin administered at 60 mg/kg suppressed tumor growth and metastasis in mouse models without causing significant toxicity. Taxifolin modulated USP18/Rac1/JNK/ß-catenin axis to exert its antitumor effect. CONCLUSION: These findings indicate that Taxifolin derived from Larix olgensis roots may be a promising antimelanoma therapy.

A wave energy driven high-performance self-powered oil spill positioner.

The oil spill positioner is capable of real-time monitoring oil films on the sea surface. However, the lack of high-performance power supply methods greatly restricts the application of oil spill positioner. In this research, we design a high-performance self-powered oil spill positioner based on a soft-contact-triboelectric-nanogenerator (SC-TENG). This device achieves soft-contact by attaching rabbit fur to the rotor, which can effectively reduce frictional resistance, quickly transfer charge to the electrode, and improve the durability of the parts. First, we calculate the highest occupied molecular orbital and the lowest unoccupied molecular orbital of polytetrafluoroethylene (PTFE) and polyvinylidene fluoride (PVDF) molecules through first-principles simulations, and compared the ease of electron excitation between the two materials. The results show that the performance of SC-TENG with PVDF as dielectric material is significantly better than that of PTFE. At the same time, this phenomenon has been confirmed by experiments. On the basis of experimental and simulate research on two types of power management circuits, a bridge rectifier circuit with the function of converting alternating current to direct current is selected to realize the self-power supply of the oil spill positioner. Additionally, by optimizing the structure of the SC-TENG and employing a bridge rectifier circuit, the SC-TENG can achieve a maximum open-circuit voltage of 1400 V and a short-circuit current of 3.49µA, which are enough to light up 200 light-emitting diodes and power the oil spill positioner. Finally, we simulate the open-circuit voltage and short-circuit current of the SC-TENG on a six-degree-of-freedom platform and test its durability under real-world ocean wave conditions, all of which show excellent performance. This work develops an efficient wave energy conversion mechanism and successfully realizes the high-performance self-powering of the oil spill positioner, making oil spill monitoring more flexible and reliable.

Efficacy and safety of innate and adaptive immunotherapy combined with standard of care in high-grade gliomas: a systematic review and meta-analysis.

Background: Malignant glioma is the most common intracranial malignant tumor with the highest mortality. In the era of immunotherapy, it is important to determine what type of immunotherapy provides the best chance of survival. Method: Here, the efficacy and safety of immunotherapy in high-grade glioma (HGG) were evaluated by systematic review and meta-analysis. The differences between various types of immunotherapy were explored. Retrieved hits were screened for inclusion in 2,317 articles. We extracted the overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) as two key outcomes for examining the efficacy of immunotherapy. We also analyzed data on the reported corresponding adverse events to assess the safety of immunotherapy. This study was registered with PROSPERO (CRD42019112356). Results: We included a total of 1,271 patients, of which 524 received a combination of immunotherapy and standard of care (SOC), while 747 received SOC alone. We found that immunotherapy extended the OS (HR = 0.74; 95% confidence interval [CI], 0.56-0.99; Z = -2.00, P = 0.0458 < 0.05) and PFS (HR = 0.67; 95% CI, 0.45-0.99; Z = -1.99, P = 0.0466 < 0.05), although certain adverse events occurred (proportion = 0.0773, 95% CI, 0.0589-0.1014). Our data have demonstrated the efficacy of the dendritic cell (DC) vaccine in prolonging the OS (HR = 0.38; 95% CI, 0.21-0.68; Z = -3.23; P = 0.0012 < 0.05) of glioma patients. Oncolytic viral therapy (VT) only extended patient survival in a subgroup analysis (HR = 0.60; 95% CI, 0.45-0.80; Z = -3.53; P = 0.0004 < 0.05). By contrast, immunopotentiation (IP) did not prolong OS (HR = 0.69; 95% CI, 0.50-0.96; Z = -2.23; P = 0.0256). Conclusion: Thus, DC vaccination significantly prolonged the OS of HGG patients, however, the efficacy of VT and IP should be explored in further studies. All the therapeutic schemes evaluated were associated with certain side effects. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=112356.

DNA methylation meningioma biomarkers: attributes and limitations.

Meningioma, one of the most common primary central nervous system tumors, are classified into three grades by the World Health Organization (WHO) based on histopathology. The gold-standard treatment, surgical resection, is hampered by issues such as incomplete resection in some cases and a high recurrence rate. Alongside genetic alterations, DNA methylation, plays a crucial role in progression of meningiomas in the occurrence and development of meningiomas. The epigenetic landscape of meningioma is instrumental in refining tumor classification, identifying robust molecular markers, determining prognosis, guiding treatment selection, and innovating new therapeutic strategies. Existing classifications lack comprehensive accuracy, and effective therapies are limited. Methylated DNA markers, exhibiting differential characteristics across varying meningioma grades, serve as invaluable diagnostic tools. Particularly, combinatorial methylated markers offer insights into meningioma pathogenesis, tissue origin, subtype classification, and clinical outcomes. This review integrates current research to highlight some of the most promising DNA and promoter methylation markers employed in meningioma diagnostics. Despite their promise, the development and application of DNA methylation biomarkers for meningioma diagnosis and treatment are still in their infancy, with only a handful of DNA methylation inhibitors currently clinically employed for meningioma treatment. Future studies are essential to validate these markers and ascertain their clinical utility. Combinatorial methylated DNA markers for meningiomas have broad implications for understanding tumor development and progression, signaling a paradigm shift in therapeutic strategies for meningiomas.

A cascade targeting strategy based on modified bacterial vesicles for enhancing cancer immunotherapy.

BACKGROUND: As an efficient tumor immunotherapy, PD-1 antibody has been gradually used in clinical tumor treatment, but the low response rate and excessive immune response limit its extensive application. RESULTS: Herein, a therapeutic regime for the reinvigoration and activation of the tumor immune microenvironment is introduced to improve the anti-tumor effect of the PD-1 antibody. To comprehensively improve the effect of the immunotherapy and reduce excessive immune response, a biomimetic cascade targeting nanosystem, siRNA@PLOV, which was fused by photothermal sensitive liposomes (PTSLs) and attenuated Salmonella outer membrane vesicles (OMVs), was administered in the tumor therapy for targeting of tumor tissues and T cells within tumor respectively. The fused PLOVs which not only retained the biological character of the OMVs, but also enhanced the drug loading ability. The results demonstrated that the immunogenicity of OMVs and photothermal effects can obviously increase the infiltration of T cells and the silencing of CD38 can effectively improve the T cell cytotoxicity, especially combining with PD-1 antibody. CONCLUSIONS: Interesting, this study revealed that anti-PD-1 administration on the 5th day after siRNA@PLOV treatment had the best performance in killing tumors compared with other groups. In addition, this new therapeutic regime also presents a novel strategy for inducing "vaccine effects", conclusively highlighting its potential in preventing tumor recurrence and improving prognosis.

INTS8 is a therapeutic target for intrahepatic cholangiocarcinoma via the integration of bioinformatics analysis and experimental validation.

Intrahepatic cholangiocarcinoma (CHOL) remains a rare malignancy, ranking as the leading lethal primary liver cancer worldwide. However, the biological functions of integrator complex subunit 8 (INTS8) in CHOL remain unknown. Thus, this research aimed to explore the potential role of INTS8 as a novel diagnostic or therapeutic target in CHOL. Differentially expressed genes (DEGs) in two Gene Expression Omnibus (GEO) datasets were obtained by the "RRA" package in R software. The "maftools" package was used to visualize the CHOL mutation data from The Cancer Genome Atlas (TCGA) database. The expression of INTS8 was detected by performing quantitative reverse transcription-PCR (qRT-PCR) and immunohistochemistry in cell lines and human samples. The association between subtypes of tumour-infiltrating immune cells (TIICs) and INTS8 expression in CHOL was determined by using CIBERSORT tools. We evaluated the correlations between INTS8 expression and mismatch repair (MMR) genes and DNA methyltransferases (DNMTs) in pan-cancer analysis. Finally, the pan-cancer prognostic signature of INTS8 was identified by univariate analysis. We obtained the mutation landscapes of an RRA gene set in CHOL. The expression of INTS8 was upregulated in CHOL cell lines and human CHOL samples. Furthermore, INTS8 expression was closely associated with a distinct landscape of TIICs, MMR genes, and DNMTs in CHOL. In addition, the high INTS8 expression group presented significantly poor outcomes, including overall survival (OS), disease-specific survival (DSS) and disease-free interval (DFI) (p < 0.05) in pan-cancer. INTS8 contributes to the tumorigenesis and progression of CHOL. Our study highlights the significant role of INTS8 in CHOL and pan-cancers, providing a valuable molecular target for cancer research.

Depletion of glioma stem cells by synergistic inhibition of mTOR and c-Myc with a biological camouflaged cascade brain-targeting nanosystem.

Glioma stem cells (GSCs), as a subpopulation of stem cell-like cells, have been proposed to play a crucial role in the progression of drug-resistance in glioblastoma (GBM). Therefore, the targeted eradication of GSCs can serve as a promising therapeutic strategy for the reversal of drug-resistance in GBM. Herein, the effects of silencing c-Myc and m-TOR on primary GBM cells extracted from patients were investigated. Results confirmed that dual inhibition treatment significantly (p < 0.05) and synergistically suppressed GSCs, and consequently reversed TMZ-resistance when compared with the single treatment group. Subsequently, to facilitate effective crossing of the BBB, a biological camouflaged cascade brain-targeting nanosystem (PMRT) was created. The PMRT significantly inhibited tumor growth and extended the lifespan of orthotopic transplantation TMZ-resistant GBM-grafted mice. Our data demonstrated that PMRT could precisely facilitate drug release at the tumor site across the BBB. Simultaneously, c-Myc and m-TOR could serve as synergistic targets to eradicate the GSCs and reverse GBM resistance to TMZ.

HOTAIR/miR-125 axis-mediated Hexokinase 2 expression promotes chemoresistance in human glioblastoma.

Drug resistance is one of the major obstacles in glioblastoma (GBM) treatments using temozolomide (TMZ) based conventional chemotherapy. Recent studies revealed that Hexokinase 2 (HK2)-mediated glycolysis is one of the sources, as the association of chemoresistance and the expression of HK2 was confirmed in multiple cancers. However, there has been little knowledge of the functional contribution of HK2 to TMZ resistance in GBM. In our study, we found that HK2 expression is crucial for GBM proliferation and chemoresistance. In contrast to the healthy brain, HK2 expression is much higher in human GBM, especially in those patients with GBM recurrence. High HK2 expression is negatively related to the overall survival in GBM patients. HK2 depletion in GBM cells suppressed the GBM cell proliferation and increased sensitivity to TMZ-induced apoptosis. Both HK2-mediated glycolysis and mitochondria permeability transition pore opening (MPTP) were associated with its function in chemoresistance. Furthermore, we also revealed that the abnormal expression of HK2 was modulated by the expression of HOTAIR, a long non-coding RNA (lncRNA). The absence of HOTAIR in GBM cells suppressed the HK2 expression in protein and mRNA level and, therefore, inhibited the cell proliferation and enhanced the cytotoxicity of TMZ both in vivo and in vitro. HOTAIR promoted the expression of HK2 by targeting mir-125, which suppressed the GBM cell proliferation and increased the TMZ-induced apoptosis. These findings shed light on a new therapeutic strategy in modulating HOTAIR/miR-125, which may interfere with the expression of HK2, and enhance the therapeutic sensitivity of GBM to TMZ.

Multiple primary central nervous system lymphoma in the elderly: A case report.

RATIONALE: Multiple primary central nervous system lymphoma (MPCNSL) is a rare disease with differential diagnosis and treatment. As the underlying pathogenesis is not yet clarified, the early-stage clinical manifestations are occult and atypical. Also, the imaging manifestations are not specific, which is challenging for the clinical diagnosis and treatment. Therefore, additional clinical research is essential to understand the etiology of the disease. PATIENT CONCERNS: A 63-year-old male patient suffered from MPCNSLs but without typical clinical manifestations. The findings of the imaging examination were as follows. Magnetic resonance imaging (MRI) showed long T1 and T2 signal shadows in the right frontal lobe, right hippocampus, right cerebellar hemisphere, and the left occipital lobe. In addition, patchy T1-enhanced signal shadows were observed in the right frontal lobe and around the midline. Frontal lesions were detected in the magnetic resonance spectroscopy (MRS), Cho peak increased, and N-acetylaspartate (NAA) peak decreased. On the other hand, in the diffusion weighted imaging (DWI), apparent dispersion coefficient (ADC) showed low-value changes and high signal changes. The positron emission tomography-computed tomography (PET-CT) displayed radioactive accumulation in the right frontal lobe. DIAGNOSIS: Multiple primary central nervous system lymphoma. INTERVENTIONS: The patient received some conservative medical treatment, but his condition continued to worsen. Finally, he received a pathological biopsy, and refused further treatment after the result was reported. OUTCOMES: The patient died 1 week after biopsy, and the course of disease was about 100 days. LESSONS: PCNSL is a primary intracranial malignancy with low incidence and a high degree of malignancy and specificity in clinical manifestations. To facilitate early clinical treatment and improve the long-term survival of patients, it is necessary to master the imaging diagnostic methods and its features. The comprehensive application of multiple imaging examinations, such as CT, MRI, PET/CT, and PET/MRI, as well as, cerebrospinal fluid cytology can greatly improve the diagnosis of PCNSL.

Short-term results of acellular porcine corneal stroma keratoplasty for herpes simplex keratitis.

BACKGROUND: Corneal transplantation is a common surgical intervention for restoring vision loss due to corneal damages. However, for cultural reasons, there is a huge shortage of donor corneas in China. Acellular porcine corneal stromas (APCSs) can be used as corneal substitutes in lamellar keratoplasty for corneal ulcers. This study was conducted to analyze the results of APCS use for herpes simplex keratitis (HSK). METHODS: The study involved HSK patients who underwent keratoplasty with APCSs from February 2016 to October 2017 in the second affiliated hospital of Zhejiang University. Patient data were collected at 7 days, 1 month, 3 months, 6 months, and at the last follow-up (7-25 months) postoperative. The corneal transparency, neovascularization, visual acuity, and graft stability were observed. RESULTS: Thirteen patients with HSK including five patients with corneal perforation were included in this study, nine patients underwent deep anterior lamellar keratoplasty (DALK) and five perforation patients underwent double lamellar keratoplasty. There were nine men and four women with an average age of 62.5 ± 5.6 years old (ranging from 52 to 70 years old). The mean postoperative follow-up duration was 15.1 ± 5.8 months (ranging from 7 to 25 months). At the last visit, visual acuity improved in nine patients (69.2%) compared with preoperative (P = 0.008).The grafts of seven individuals (53.8%) were completely transparent or slightly opaque; their corneal transparency score had improved significantly compared with before the surgery (P = 0.010). Various degrees of neovascularization were present in 11 of the 13 patients (84.6%), most neovascularization gradually stabilized. Graft dissolution occurred in three eyes (23.1%) during the observation period, two underwent regrafting, the other one became stable after treatment. Three patients underwent second allograft transplantation, two of which encountered APCS graft dissolution and one of the patients requested a human donor allograft transplantation due to transparency issues despite the absence of adverse issues. CONCLUSION: Acellular porcine corneal stroma seems to be effective in the treatment of HSK and can be used in HSK with corneal perforation by using double lamellar keratoplasty in an emergency.

Therapeutic evaluation of a patient with ruptured intracranial aneurysm without subarachnoid hemorrhage by CT imaging: a case report.

BACKGROUND: The majority of ruptured intracranial aneurysms are combined with subarachnoid hemorrhage, but patients with only intracerebral hematoma without any subarachnoid hemorrhage are extremely rare. CASE PRESENTATION: The patient was hospitalized due to sudden dizziness combined with slurred speech. The patient showed considerable decreased physical activity without any nuchal rigidity. Head CT showed hematoma in the left temporal lobe, and the shape of hematoma was extremely irregular. MRI indicated the absence of any vascular malformations. The patient was diagnosed with middle cerebral artery bifurcation aneurysm in the left by head CTA. Intracranial aneurysm clip and removal of hematoma in the left temporal lobe were performed under general anesthesia. The patient did not show any significant neurological dysfunction after the surgery and was followed up for 4 months after discharge with GOS score of 5 points. CONCLUSIONS: Intracranial hematoma with irregular morphology around the lateral fissure of the brain should be considered critical in order to avoid misdiagnosis and any possibility of missed diagnosis of vascular lesions, so as to ensure an exact therapeutic strategy with good prognosis for the patients.

Meningeal carcinomatosis: three case-reports.

BACKGROUND: Meningeal carcinomatosis (MC) is characterized by diffuse infiltration of tumor cells in meninges. There is no tumor mass in the brain and parenchyma of the spinal cord. MC is divided into primary and metastatic types. MC cases were previously diagnosed postoperatively or at autopsy. Recent advances in spinal abbreviation cytology and imaging have led to increase in number of reported cases. In this study, we discuss the manifestations of MC patients based on magnetic resonance imaging (MRI) findings, as well as the correlation between the manifestations and pathology. CASE PRESENTATION: MC was confirmed in all three cases by lumbar puncture and gadopentetate dimeglumine-enhanced magnetic resonance imaging. Due to different primary diseases, the patients had specific imaging manifestations. CONCLUSION: Enhanced MRI examination is extremely sensitive for detecting abnormalities in meninges, which plays a very important role in the diagnosis of MC. Since meninges of some MC patients cannot be enhanced, the enhanced MRI examination cannot be replaced by conventional cerebrospinal abbreviation examination. Attribute to the diversity of MR contrast agents, which could provide higher lesion conspicuity and enhances lesion detection, there may be some more choices to improve the detection rate of MC patients and prolong their survival lifetime.

Near-infrared light-activatable siRNA delivery by microcapsules for combined tumour therapy.

A polyelectrolyte microcapsule-based layer-by-layer (LbL) technique has been widely used as a multifunctional vehicle for combined tumor therapy. Meanwhile, with the rapid development of combined tumour therapy, the challenge for designing multifunctional drug delivery system has attracted much more attention. Herein, we developed a new type of microcapsule (MC) system called MPA@siRNA@DOX@MC, which conjugated with siRNA and DOX as well as ICG-Der-02 (MPA) by electrostatic absorption. MPA as indocyanine green (ICG) fluorescence dye, exhibiting high fluorescence emission and photothermal conversion ability under NIR laser irradiation, was uploaded onto this drug system for realizing the controllable drug release and cancer theranostics. In addition, the results revealed that MPA@siRNA@DOX@MC possessed several ideal properties including high drug-loading capacity, excellent siRNA transfection efficiency, siRNA sequence protection and remarkably improved tumour-targeting capacity. Moreover, the combined therapy based on this drug system displayed improved therapeutic efficacy and negligible side effects both in vivo and in vitro experiment. Ultimately, MPA@siRNA@DOX@MC drug delivery system successfully combined the photothermal therapy and chemotherapy with controlled siRNA sequence silencing may have a promising potential in combined tumor therapy.

TT-1, an analog of melittin, triggers apoptosis in human thyroid cancer TT cells via regulating caspase, Bcl-2 and Bax.

Melittin is a 26 amino acid residue antimicrobial peptide with known antitumor activity. In the present study, a novel peptide TT-1, derived from melittin and contained only 11 amino acids, was designed, and its antitumor effect was investigated. The present study is aimed to elucidate the effects and relative mechanisms of TT-1 on a human thyroid cancer cell line (TT) in vitro and in vivo. Cell viability assays, Annexin V/propidium iodide assays, western blotting and quantitative reverse transcription polymerase chain reaction were performed. Furthermore, a tumor-xenograft model was established to investigate the apoptotic mechanisms of TT-1 on TT cells. The results obtained indicated that TT-1 was able to suppress the proliferation of TT cells and exhibited low cytotoxicity to normal thyroid cells in vitro. The apoptotic rates of TT cells were also increased following TT-1 treatment. Additionally, TT-1 stimulated caspase-3, caspase-9 and Bax, and inhibited B-cell lymphoma 2 mRNA and protein expression. Finally, it was also demonstrated that TT-1 is able to markedly suppress tumor growth in a TT-bearing nude mouse model. In summary, TT-1 may inhibit the proliferation of TT cells by inducing apoptosis in vitro and in vivo, indicating that TT-1 may be a potential candidate for the treatment of thyroid cancer.

Circular RNA profile indicates circular RNA VRK1 is negatively related with breast cancer stem cells.

Circular RNAs (circRNAs), a novel type of noncoding RNAs (ncRNAs), have been shown to be implicated in biological processes including cancer as gene expression regulators. However, the roles of circRNAs in cancer stem cells (CSCs) have been unexplored. In the present study, we screened the circRNA profile in breast cancer stem cells (BCSCs) using RNA-Sequencing. Here, 27 circRNAs were found to be aberrantly expressed. Of these, 19 circRNAs were downregulated and 8 were upregulated and some of these circRNAs were validated by Q-PCR. Furthermore, we constructed the circRNA/miRNA network by bioinformatics approaches and hypothesized that circRNAs might be involved in stemness of BCSCs via serving as miRNA sponges. Importantly, we found that circular RNA VRK1 (circVRK1) could suppress BCSC's expansion and self-renewal capacity. Collectively, the present work provides the first reported evidence of the circRNA profile and circRNA/miRNA interplay in BCSCs. In addition, these findings lay foundation to explore the functions of circRNAs in CSCs and indicate that circVRK1 might be a promising target for BCSCs.