ZSM-5@ceramic foam composite catalyst derived from spent bleaching clay for continuous pyrolysis of waste oil to produce monocyclic aromatic hydrocarbons.

Spent bleaching clay, a solid waste generated during the refining process of vegetable oils, lacks an efficient treatment solution. In this study, spent bleaching clay was innovatively employed to fabricate ceramic foams. The thermal stability analysis, microstructure, and crystal phase composition of the ceramic foams were characterized by TG-DSC, SEM, and XRD. An investigation into the influence of Al2O3 content on the ceramic foams was conducted. Results showed that, as the Al2O3 content increased from 15 wt% to 30 wt%, there was a noticeable decrease in bulk density and linear shrinkage, accompanied by an increase in compressive strength. Additionally, the ceramic foams were used as catalyst supports, to synthesize ZSM-5@ceramic foam composite catalysts for pyrolysis of waste oil. The open pores of the ZSCF catalyst not only reduced diffusion path length but also facilitated the exposure of more acid sites, thereby increasing the utilization efficiency of ZSM-5 zeolite. This, in turn, engendered a significant enhancement in monocyclic aromatic hydrocarbons content from 39.15 % (ZSM-5 powder catalyst) to 78.96 %. Besides, a larger support pore size and a thicker ZSM-5 zeolite coating layer led to an increase in monocyclic aromatic hydrocarbons content. As the time on stream was extended to 56 min, the monocyclic aromatic hydrocarbon content obtained with the composite catalyst remained 12.41 % higher than that of the ZSM-5 powder catalyst. These findings validate the potential of the composite catalyst. In essence, this study advances the utilization of spent bleaching clay and introduces a novel concept for ceramic foam fabrication. Furthermore, it contributes to the scaling up of catalytic pyrolysis technology.

A Multimodal Ultrasound Observation Study on the Effect of Vitamin D on Uterine Fibroids in Non-menopausal Women.

INTRODUCTION: It has been reported in the literature that Vitamin D can inhibit the growth of uterine fibroids, but the evaluation index is only the size of the uterine fibroids. The purpose of this study was to evaluate the effect of vitamin D on the size, hardness, and blood flow of uterine fibroids in premenopausal women by multimodal ultrasound. METHODS: A total of 64 pre-menopausal women with uterine fibroids complicated vitamin D deficiency were enrolled in this study and randomly divided into two groups: the vitamin D group (n=32) which received oral vitamin D (1600 IU/ day) and the control group (n=32) without vitamin D supplementation. After three months of intervention, the mean diameter of uterine fibroids, elastic strain ratio, and blood flow grade were evaluated by multimodal ultrasound, and the clinical symptoms of the two groups were evaluated by questionnaire. RESULTS: The vitamin D group reported a significant increment in the serum 25-hydroxyvitamin D (P < 0.001). In addition, there were significant reductions in the mean diameter, and elastic strain ratio of uterine fibroids (P =.043 and P =.038, respectively), but no significant difference in the blood flow grade of uterine fibroids was observed (P =.272). Compared with the control group, the vitamin D group achieved significant relief in dysmenorrhea and frequent urination, as well as improvement in heavy menstrual bleeding. CONCLUSION: The application of multimodal ultrasound provides a more comprehensive theoretical basis for vitamin on uterine fibroids. Vitamin D can effectively reduce the size of uterine fibroids in pre-menopausal women and relieve their symptoms. It is highly likely to be a promising, safe, effective, and inexpensive drug for uterine fibroids, which has good application value and promotion prospects.

The novel role of activating receptor KIR2DS5 in preeclampsia.

Preeclampsia (PE) is a serious complication of pregnancy. Decidual natural killer (dNK) cells were reported to participate in the remodeling of spiral arteries through producing a group of cytokines, including granulocyte-macrophage colony stimulating factor (GM-CSF). KIR2DS5 is an activating receptor of NK cells that specifically recognizes HLA-C2 on trophoblasts. Currently, there are no reports regarding the precise mechanism of KIR2DS5 in PE. This study included 30 PE patients and 30 healthy pregnant women. We found that the expressions of KIR2DS5 were significantly lower in PE deciduae compared to those of healthy pregnancies. By transfecting knockdown and overexpression lentivirus vectors of KIR2DS5 into dNK cells isolated from deciduae of early pregnancy, we altered the KIR2DS5 expression level in dNK cells. Then, these dNK cells and trophoblast cell lines were co-cultured as trophoblast-dNK cells. In the trophoblast-dNK cells, we examined the influence of KIR2DS5 on the biological manifestations of trophoblasts. As anticipated, overexpression of KIR2DS5 could facilitate cell proliferation, migration, and invasion. Furthermore, increased expression of KIR2DS5 inhibited cell apoptosis and enhanced the progression of cells from theG1 to theS stage. Further mechanistic study demonstrated a positive relationship between KIR2DS5 and GM-CSF in trophoblast-dNK cells. Accordingly, our observations indicated that a decrease in KIR2DS5 could reduce the expression of GM-CSF via the JAK2/STAT5 pathway, resulting in the failure of the activated signal to be transmitted to dNK cells and ultimately leading to the occurrence of PE. KIR2DS5 may be a new contributor for the prediction and diagnosis of PE.

Early postsurgical lethal outcome due to splenic littoral cell angioma: A case report.

BACKGROUND: Littoral cell angioma (LCA) is a rare benign vascular tumor of the spleen. Given its rarity, standard diagnostic and therapeutic recommendations have yet to be developed for reported cases. Splenectomy is the only method of obtaining a pathological diagnosis and providing treatment to obtain a favorable prognosis. CASE SUMMARY: A 33-year-old female presented with abdominal pain for one month. Computed tomography and ultrasound revealed splenomegaly with multiple lesions and two accessory spleens. The patient underwent laparoscopic total splenectomy and accessory splenectomy, and splenic LCA was confirmed by pathology. Four months after surgery, the patient presented with acute liver failure, was readmitted, rapidly progressed to multiple organ dysfunction syndrome and died. CONCLUSION: Preoperative diagnosis of LCA is challenging. We systematically reviewed online databases to identify the relevant literature and found a close relationship between malignancy and immunodysregulation. When a patient suffers from both splenic tumors and malignancy or immune-related disease, LCA is possible. Due to potential malignancy, total splenectomy (including accessory spleen) and regular follow-up after surgery are recommended. If LCA is diagnosed after surgery, a comprehensive postoperative examination is needed.

Triptonide inhibits growth and metastasis in HCC by suppressing EGFR/PI3K/AKT signaling.

Liver cancer represents one of the deadliest cancers, with a rising incidence worldwide. Triptonide is found in the traditional Chinese medicinal plant Tripterygium wilfordii Hook. This study aimed to examine the anticancer properties of triptonide in human hepatocellular carcinoma (HCC). HCC cells were administered with triptonide at various levels, and CCK-8 and colony formation assays were carried out for detecting HCC cell proliferation. Then, cell apoptosis and cell cycle distribution were evaluated by flow cytometry. Tumor growth was monitored noninvasively by ultrasound imaging. Cell migration and invasion were quantitated by wound healing and Transwell assays. A metastasis model was established via tail vein injection of HCC cells in nude mice. Immunoblot was performed to quantitate the expression of proteins involved in the EGFR/PI3K/AKT signaling and its downstream effectors. Triptonide repressed cell proliferation and induced cell cycle arrest and apoptosis in cultured HCC cells, and suppressed tumor growth in vivo. In addition, triptonide inhibited EMT, migration and invasion in cultured HCC cells, and lung metastasis in nude mice. Mechanistically, triptonide acted by inhibiting the EGFR/PI3K/AKT signaling and regulated its downstream effectors, e.g., the cell cycle-associated protein cyclin D1, the apoptosis-related protein Bcl-2, the EMT marker E-cadherin, and the invasion-related protein MMP-9. Triptonide suppresses proliferation, EMT, migration and invasion, and promotes apoptosis and cell cycle arrest by repressing the EGFR/PI3K/AKT signaling. Therefore, triptonide might be considered for liver cancer treatment.

Evaluating glioma-associated microRNA by complementation on a biological nanosensor.

Glioma is a tumor in the brain and spinal cord originating in the glial cells that surround the nerve cells. Among several microRNAs reported, miRNA-363 is associated with human glioma. Based on miRNA-363 levels, the development and progression of glioma can be monitored. The current study used an interdigitated electrode sensor to monitor microRNA-363 levels, which indeed reflects the severity of glioma. The interdigitated electrode was generated using a photolithography technique followed by surface chemical modification carried out to insert miRNA-363 complementary oligo as the probe complexed with gold nanoparticles. The proposed sensor works based on the dipole moment between two electrodes, and when molecular immobilization or interaction occurs, the response by the signal output changes. The changes in the target microRNA-363 sequence were standardized to identify glioma. The limit of detection of miRNA-363 was 10 fM with an R2 value of 0.996 on the linear coefficient regression ranges between 1 fM and 100 pM. Furthermore, unrelated sequences failed to increase the response of the current with the complementary probe, indicating specific miRNA-363 detection on the interdigitated electrode. This study demonstrates the platform to be used for determining the presence of microRNA-363 in glioma and as the basis for other biomarker analyses.

CCL2-targeted ginkgolic acid exerts anti-glioblastoma effects by inhibiting the JAK3-STAT1/PI3K-AKT signaling pathway.

AIMS: Glioblastoma (GBM) with aggressive nature and poor prognosis has become the most common intracranial tumor. Most clinical chemotherapeutic drugs fail to achieve the anticipated therapeutic outcome. This study identified the anti-GBM effects of ginkgolic acids (GAs) and elucidated the potential molecular mechanisms, exploiting the significant antitumor effects of GAs, which are widely present in the outer bark of Ginkgo biloba. MATERIALS AND METHODS: Two GBM cell lines, U251 and T98G, were selected for in vitro experiments to evaluate the antitumor effects of GA. Cell viability and proliferation were examined by MTT and colony formation assay. The effect of GA on apoptosis and the cell cycle was examined by flow cytometry. Scratch and Transwell assays reflected the migration and invasion ability. The molecular mechanisms were explored by using immunoblot analysis, RNA sequencing and bioinformatics. In the nude mouse transplantation tumor model, preclinical treatment effects were assessed by ultrasound and MRI. KEY FINDINGS: The present study showed that GA inhibited the proliferation, migration, invasion, stemness, epithelial-to-mesenchymal transition (EMT) of GBM cells and induced apoptosis by inhibiting CCL2, affecting the JAK-STAT and PI3K-AKT signaling pathways, and inhibiting the EMT regulators Snail and Slug. Finally, GA showed significant control of tumors in a GBM xenograft model. SIGNIFICANCE: GA inhibits the progression of GBM cells by targeting CCL2, affecting the JAK-STAT and PI3K-AKT signaling pathways, and inhibiting the EMT regulators Snail and Slug. The outstanding antitumor properties of GA provide a novel strategy for the GBM therapy.

Multifunctional Drug-Loaded Phase-Change Nanoparticles Inhibit the Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma by Affecting the Activity of Activated Hepatic Stellate Cells.

Objectives. Preparation of a multifunctional drug-loaded phase-change nanoparticle (NP), pirfenidone perfluoropentane liposome NPs (PPL NPs), and combined with low-intensity focused ultrasound (LIFU) to influence epithelial mesenchymal transition (EMT) for hepatocellular carcinoma (HCC) by inhibiting the activity of activated Hepatic Stellate Cells (a-HSCs). Methods. PPL NPs were prepared by the thin film dispersion method. The appearance, particle size, zeta potential, encapsulation efficiency, drug loading rate, drug release in vitro, and stability of PPL NPs were tested. The role of a-HSCs in HCC metastasis was studied by CCK-8, colony formation assay, apoptosis, cellular uptake assay, wound healing assay, and Transwell assay. Western blot was used to detect the related protein expression levels. In vitro and vivo, the acoustic droplet vaporization (ADV) of PPL NPs was tested at different times and LIFU intensities. Biosafety of the PPL NPs was assessed by measuring nude mouse body weight and hematoxylin and eosin (H&E) staining. Results. The results showed that the PPL NPs had good biosafety, with an average particle size of 346.6 ± 62.21 nm and an average zeta potential of -15.23 mV. When the LIFU power is 2.4 W/cm2, it can improve the permeability of cells, further promote the uptake of drugs by cells, and improve the toxicity of drugs. In vitro experiments showed that PPL NPs could inhibit the proliferation of a-HSCs cells, thereby affecting the metastasis of HCC, and were related to the TGFß-Smad2/3-Snail signaling pathway. Both in vivo and in vitro PPL NPs enhanced ultrasound imaging by LIFU-triggered ADV. Conclusion. The PPL NPs designed and prepared in this study combined with LIFU irradiation could significantly alter the EMT of HCC by inhibiting LX2. Clinically, PPL NPs will also be considered a promising contrast agent due to their ultrasound imaging capabilities.

Targeting the TREM1-positive myeloid microenvironment in glioblastoma.

Background: Tumor cellular and molecular heterogeneity is a hallmark of glioblastoma and underlies treatment resistance and recurrence. This manuscript investigated the myeloid-derived microenvironment as a driver of glioblastoma heterogeneity and provided a pharmacological pathway for its suppression. Methods: Transcriptomic signatures of glioblastoma infiltrated myeloid-derived cells were assessed using R2: genomic platform, Ivy Glioblastoma Spatial Atlas, and single-cell RNA-seq data of primary and recurrent glioblastomas. Myeloid-derived cell prints were evaluated in five PDX cell lines using RNA-seq data. Two immunocompetent mouse glioblastoma models were utilized to isolate and characterize tumor-infiltrated myeloid-derived cells and glioblastoma/host cell hybrids. The ability of an inhibitor of HuR dimerization SRI42127 to suppress TREM1+-microenvironment and glioblastoma/myeloid-derived cell interaction was assessed in vivo and in vitro. Results: TREM1+-microenvironment is enriched in glioblastoma peri-necrotic zones. TREM1 appearance is enhanced with tumor grade and associated with poor patient outcomes. We confirmed an expression of a variety of myeloid-derived cell markers, including TREM1, in PDX cell lines. In mouse glioblastoma models, we demonstrated a reduction in the TREM1+-microenvironment and glioblastoma/host cell fusion after treatment with SRI42127. In vitro assays confirmed inhibition of cell fusion events and reduction of myeloid-derived cell migration towards glioblastoma cells by SRI42127 and TREM1 decoy peptide (LP17) versus control treatments. Conclusions: TREM1+-myeloid-derived microenvironment promulgates glioblastoma heterogeneity and is a therapeutic target. Pharmacological inhibition of HuR dimerization leads to suppression of the TREM1+-myeloid-derived microenvironment and the neoplastic/non-neoplastic fusogenic cell network.

Inhibition of the RNA Regulator HuR by SRI-42127 Attenuates Neuropathic Pain After Nerve Injury Through Suppression of Neuroinflammatory Responses.

Microglial activation with the production of pro-inflammatory mediators such as IL-6, TNF-α, and IL-1ß, is a major driver of neuropathic pain (NP) following peripheral nerve injury. We have previously shown that the RNA binding protein, HuR, is a positive node of regulation for many of these inflammatory mediators in glia and that its chemical inhibition or genetic deletion attenuates their production. In this report, we show that systemic administration of SRI-42127, a novel small molecule HuR inhibitor, attenuates mechanical allodynia, a hallmark of NP, in the early and chronic phases after spared nerve injury in male and female mice. Flow cytometry of lumbar spinal cords in SRI-42127-treated mice shows a reduction in infiltrating macrophages and a concomitant decrease in microglial populations expressing IL-6, TNF-α, IL-1ß, and CCL2. Immunohistochemistry, ELISA, and qPCR of lumbar spinal cord tissue indicate suppression of these cytokines and other inflammatory mediators. ELISA of plasma samples in the acute phase also shows attenuation of inflammatory responses. In summary, inhibition of HuR by SRI-42127 leads to the suppression of neuroinflammatory responses and allodynia after nerve injury and represents a promising new direction in the treatment of NP.

The role of plasminogen activator inhibitor-1 in gynecological and obstetrical diseases: An update review.

In a normal pregnancy, maternal circulatory system presents a hypercoagulable state due to the effect of hormone secretion. Even minor variations in fibrinolytic system could lead to hyper- or hypofibrinolysis, affecting placental formation, and causing adverse pregnancy outcomes. Plasminogen activator inhibitor-1 (PAI-1) restrains the fibrinolysis cascade. A controversial relationship exists regarding the role of PAI-1 in gynecological and obstetrical diseases. In this review, the authors focused on discussing the sophisticated roles of PAI-1 gene in adverse pregnancy complications and gynecological conditions, which include recurrent pregnancy loss (RPL), preeclampsia (PE), gestational diabetes mellitus (GDM), fetal growth restriction (FGR), repeated implantation failure (RIF), polycystic ovary syndrome (PCOS), and endometriosis. A pair of autonomous authors searched the literature in PUBMED, Web of Science, and Google Scholar databases from January 1, 1988 to October 1, 2021. PAI-1 4 G/5 G polymorphism plays a crucial part in the advancement of RPL via the change of metabolic, thrombotic, and immune issues. Moreover, PAI-1 may have a relationship with the occurrence and development of PE. In FGR, overexpression of PAI-1 leads to the excessive deposition of fibrin and diminished blood flow at the maternal-fetal interface, which affects the growth and development of the fetus. PAI-1 expression can be decreased by physical exercise and medical treatments, including metformin. In the future, extensive researches with rigorous inclusion standards involving diverse ethnic groups are needed to explore the functionality of PAI-1 in related gynecological and obstetrical diseases, and may be helpful to develop novel treatment methods to prevent or treat these diseases.

Chelerythrine inhibits the progression of glioblastoma by suppressing the TGFB1-ERK1/2/Smad2/3-Snail/ZEB1 signaling pathway.

AIMS: Glioblastoma (GBM) is the most common and aggressive intracranial tumor with poor prognosis. A large majority of clinical chemotherapeutic agents cannot achieve the desired therapeutic effect. Chelerythrine (CHE), a natural component with multitudinous pharmacological functions, has been proven to have outstanding antitumor effects in addition to antibacterial, anti-inflammatory, and hypotensive effects. However, the anti-GBM effect of CHE has not been reported to date. The purpose of this paper is to observe the anti-GBM effect of CHE and further explore the related mechanism. MATERIALS AND METHODS: GBM cell lines (U251 and T98G) and BALB/c nude mice were used in the experiments. Methyl thiazolyl tetrazolium (MTT) and clone formation assays were applied to detect the viability, proliferation and stemness of GBM cells. Flow cytometry was utilized to identify the effect of CHE on GBM apoptosis. Scratch and Transwell experiments reflected the migration and invasion of cells. In vivo, xenograft tumors were implanted subcutaneously in nude mice. The progression of tumors was assessed by ultrasound and magnetic resonance imaging. Finally, western blot, bioinformatics, and immunohistochemistry experiments were used to explore the molecular mechanisms in depth. KEY FINDINGS: In vitro tests showed that CHE inhibited the proliferation, stemness, migration, and invasion of GBM cells and induced apoptosis. In vitro, CHE was observed to restrain the progression of xenograft tumors. We eventually proved that the cytotoxicity of CHE was relevant to the TGFB1-ERK1/2/Smad2/3-Snail/ZEB1 signaling pathway. SIGNIFICANCE: CHE inhibited GBM progression by inhibiting the TGFB1-ERK1/2/Smad2/3-Snail/ZEB1 signaling pathway and is a potential chemotherapeutic drug for GBM.

SRI-42127, a novel small molecule inhibitor of the RNA regulator HuR, potently attenuates glial activation in a model of lipopolysaccharide-induced neuroinflammation.

Glial activation with the production of pro-inflammatory mediators is a major driver of disease progression in neurological processes ranging from acute traumatic injury to chronic neurodegenerative diseases such as amyotrophic lateral sclerosis and Alzheimer's disease. Posttranscriptional regulation is a major gateway for glial activation as many mRNAs encoding pro-inflammatory mediators contain adenine- and uridine-rich elements (ARE) in the 3' untranslated region which govern their expression. We have previously shown that HuR, an RNA regulator that binds to AREs, plays a major positive role in regulating inflammatory cytokine production in glia. HuR is predominantly nuclear in localization but translocates to the cytoplasm to exert a positive regulatory effect on RNA stability and translational efficiency. Homodimerization of HuR is necessary for translocation and we have developed a small molecule inhibitor, SRI-42127, that blocks this process. Here we show that SRI-42127 suppressed HuR translocation in LPS-activated glia in vitro and in vivo and significantly attenuated the production of pro-inflammatory mediators including IL1ß, IL-6, TNF-α, iNOS, CXCL1, and CCL2. Cytokines typically associated with anti-inflammatory effects including TGF-ß1, IL-10, YM1, and Arg1 were either unaffected or minimally affected. SRI-42127 suppressed microglial activation in vivo and attenuated the recruitment/chemotaxis of neutrophils and monocytes. RNA kinetic studies and luciferase studies indicated that SRI-42127 has inhibitory effects both on mRNA stability and gene promoter activation. In summary, our findings underscore HuR's critical role in promoting glial activation and the potential for SRI-42127 and other HuR inhibitors for treating neurological diseases driven by this activation.

The Update Immune-Regulatory Role of Pro- and Anti-Inflammatory Cytokines in Recurrent Pregnancy Losses.

Recurrent pregnancy losses (RPL) is a common reproductive disorder with various underlying etiologies. In recent years, rapid progress has been made in exploring the immunological mechanisms for RPL. A propensity toward Th2 over Th1 and regulatory T (Treg) over Th17 immune responses may be advantageous for reproductive success. In women with RPL and animals prone to abortion, an inordinate expression of cytokines associated with implantation and early embryo development is present in the endometrium or decidua secreted from immune and non-immune cells. Hence, an adverse cytokine milieu at the maternal-fetal interface assaults immunological tolerance, leading to fetal rejection. Similar to T cells, NK cells can be categorized based on the characteristics of cytokines they secrete. Decidual NK (dNK) cells of RPL patients exhibited an increased NK1/NK2 ratio (IFN-γ/IL-4 producing NK cell ratios), leading to pro-inflammatory cytokine milieu and increased NK cell cytotoxicity. Genetic polymorphism may be the underlying etiologies for Th1 and Th17 propensity since it alters cytokine production. In addition, various hormones participate in cytokine regulations, including progesterone and estrogen, controlling cytokine balance in favor of the Th2 type. Consequently, the intricate regulation of cytokines and hormones may prevent the RPL of immune etiologies. Local or systemic administration of cytokines or their antagonists might help maintain adequate cytokine milieu, favoring Th2 over Th1 response or Treg over Th17 immune response in women with RPL. Herein, we provided an updated comprehensive review regarding the immune-regulatory role of pro- and anti-inflammatory cytokines in RPL. Understanding the roles of cytokines involved in RPL might significantly advance the early diagnosis, monitoring, and treatment of RPL.

PFP@PLGA/Cu12Sb4S13-mediated PTT ablates hepatocellular carcinoma by inhibiting the RAS/MAPK/MT-CO1 signaling pathway.

Hepatocellular carcinoma (HCC) is one of the most malignant tumors in the world, and patients with HCC face a poor prognosis. The conventional therapeutic strategies for HCC have undergone a challenge-riddled evolution owing to side effects and unsatisfactory efficacy. Here, aiming to provide a new method of HCC elimination, we formulated a novel multifunctional nanocapsule (PFP@PLGA/Cu12Sb4S13, PPCu) with applications in contrast-enhanced ultrasound imaging (CEUS) and photothermal therapy (PTT). These PPCu were successfully constructed with an average diameter of 346 nm (polydispersity index, PDI = 0.276). The reinforced contrast ratio of these PPCu was determined by CEUS, revealing their promising applications in image-guided monitoring of HCC treatment. Furthermore, the excellent photoabsorption and biocompatibility indicated by organ H&E staining indicated that PPCu meet quality expectations for use as photothermal transduction agent (PTA). PPCu treatment at 50 °C and higher temperatures efficiently repressed the proliferation, induced the apoptosis and decreased the motility of HCC cells. These effects might have been results of RAS/MAPK/MT-CO1 signaling pathway inhibition. In summary, PPCu were constructed to integrate CEUS and PTT successfully into therapy, which can lead to HCC elimination through RAS/MAPK/MT-CO1 signaling pathway repression.

Pyrolysis of soybean soapstock for hydrocarbon bio-oil over a microwave-responsive catalyst in a series microwave system.

A novel Silicon carbide (SiC) foam ceramic based ZSM-5/SiC nanowires microwave-responsive catalyst was developed to upgrade the pyrolysis volatiles in a microwave-assisted series system (both the pyrolysis and catalytic systems were heated by microwave). The growth of SiC nanowires was helpful for the ZSM-5 growth on the SiC foam ceramic. Because the specific surface area of SiC foam ceramic was improved. The dielectric properties of the composite catalyst were improved due to the growth of SiC nanowires. Bio-oil composition analysis showed that area percentage of hydrocarbons and aromatic hydrocarbons could reach 80.89% and 40.48% at catalytic temperature of 450 ℃and 500 ℃, respectively. The microwave-responsive composite catalyst had good aromatization performance in microwave-assisted series system due to high dielectric properties and specific surface area. The composite catalyst performed well after five-cycle regeneration, and the hydrocarbon content could still reach 76.40%, which is 80.89% for the original catalyst.

Homoharringtonine inhibits the progression of hepatocellular carcinoma by suppressing the PI3K/AKT/GSK3ß/Slug signaling pathway.

Homoharringtonine (HHT), was first isolated from the bark of Cephalotaxus harringtonia (Knight ex J. Forbes) K. Koch and Cephalotaxus fortunei Hook trees. The bark extract is used to treat leukemia and in recent years has also been used in traditional Chinese medicine (TCM) to treat solid tumors. However, the inhibitory mechanism of HHT in the progression of hepatocellular carcinoma (HCC) is rarely studied. We aimed to evaluate the antitumor efficacy of HHT on HCC in vitro and in vivo and elucidate the underlying molecular mechanism(s). HCC cell lines, including HCCLM3, HepG2, and Huh7, were used to evaluate the antitumor efficacy of HHT in vitro. Cytotoxicity and proliferative ability were evaluated by MTT and colony formation assays. Cell cycle progression and apoptosis in HHT-treated HCC cells were evaluated by flow cytometry. To determine the migration and invasion abilities of HCC cells, wound-healing and Transwell assays were used. Finally, western blot analysis was used to reveal the proteins involved. We also established a xenograft nude mouse model for in vivo assessments of the preclinical efficacy of HHT, mainly using hematoxylin and eosin staining, immunohistochemistry, ultrasound imaging (USI), and magnetic resonance imaging (MRI). HHT suppressed the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of HCC cells, and induced cell cycle arrest at the G2 phase and apoptosis. In the HCC xenograft model, HHT showed an obvious tumor-suppressive effect. Surprisingly, Slug expression was also decreased by HHT via the PI3K/AKT/GSK3ß signaling pathway at least partially suppressed the growth of HCC via the PI3K/AKT/GSK3ß/Slug signaling pathway.

Targeting the HuR Oncogenic Role with a New Class of Cytoplasmic Dimerization Inhibitors.

The development of novel therapeutics that exploit alterations in the activation state of key cellular signaling pathways due to mutations in upstream regulators has generated the field of personalized medicine. These first-generation efforts have focused on actionable mutations identified by deep sequencing of large numbers of tumor samples. We propose that a second-generation opportunity exists by exploiting key downstream "nodes of control" that contribute to oncogenesis and are inappropriately activated due to loss of upstream regulation and microenvironmental influences. The RNA-binding protein HuR represents such a node. Because HuR functionality in cancer cells is dependent on HuR dimerization and its nuclear/cytoplasmic shuttling, we developed a new class of molecules targeting HuR protein dimerization. A structure-activity relationship algorithm enabled development of inhibitors of HuR multimer formation that were soluble, had micromolar activity, and penetrated the blood-brain barrier. These inhibitors were evaluated for activity validation and specificity in a robust cell-based assay of HuR dimerization. SRI-42127, a molecule that met these criteria, inhibited HuR multimer formation across primary patient-derived glioblastoma xenolines (PDGx), leading to arrest of proliferation, induction of apoptosis, and inhibition of colony formation. SRI-42127 had favorable attributes with central nervous system penetration and inhibited tumor growth in mouse models. RNA and protein analysis of SRI-42127-treated PDGx xenolines across glioblastoma molecular subtypes confirmed attenuation of targets upregulated by HuR. These results highlight how focusing on key attributes of HuR that contribute to cancer progression, namely cytoplasmic localization and multimerization, has led to the development of a novel, highly effective inhibitor. SIGNIFICANCE: These findings utilize a cell-based mechanism of action assay with a structure-activity relationship compound development pathway to discover inhibitors that target HuR dimerization, a mechanism required for cancer promotion.

lncRNA MALAT1 promotes cell proliferation and invasion by regulating the miR-101/EZH2 axis in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral cavity. Emerging evidence indicates that long non-coding (lnc)RNAs play a key role in the cellular processes of tumor cells, including glycolysis, growth and movement. Here, the purpose of this study was to explore the biological functions and potential mechanism of lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in OSCC. OSCC tissues and adjacent matched paraneoplastic normal tissues were collected from 20 OSCC patients. The expression of MALAT1 and miR-101 in OSCC tissues and cell lines (HSC3, SCC9, SCC15 and SCC25) were determined by real-time-polymerase chain reaction (qPCR). Caspase-3, xaspase-8 and EZH2 protein levels were determined by western blot analysis. MALAT1-mediated miRNAs were verified by bioinformatics analysis of StarBase and Luciferase reporter assay. Cell Counting Kit-8 (CCK-8) and Transwell assays were used for investigating MALAT1 effect on cell proliferation and invasion in the OSCC cells. qPCR analysis indicated that MALAT1 expression was obviously increased, and miR-101 was decreased in the OSCC tissues and cell lines. Functional studies revealed that overexpression of MALAT1 promoted OSCC cell proliferation and invasion. Further experiments revealed that miR-101 was a target of MALAT1 and that the miR-101 inhibitor abolished the effect of MALAT1 on OSCC cell proliferation and invasion. Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) acted as a downstream effecter of MALAT1 in the OSCC cells. Collectively, these findings revealed that upregulation of MALAT1 facilitated OSCC proliferation and invasion by targeting the miR-101/EZH2 axis.