Novel radiopaque ethanol injection: physicochemical properties, animal experiments, and clinical application in vascular malformations.

BACKGROUND: Despite the efficacy of absolute ethanol (EtOH), its radiolucency introduces several risks in interventional therapy for treating vascular malformations. This study aims to develop a novel radiopaque ethanol injection (REI) to address this issue. METHODS: Iopromide is mixed with ethanol to achieve radiopacity and improve the physicochemical properties of the solution. Overall, 82 male New Zealand white rabbits are selected for in vivo radiopacity testing, peripheral vein sclerosis [animals were divided into the following 5 groups (n = 6): negative control (NC, saline, 0.250 ml/kg), positive control (EtOH, 0.250 ml/kg), low-dose REI (L-D REI, 0.125 ml/kg), moderate-dose REI (M-D REI, 0.250 ml/kg), and high-dose REI (H-D REI 0.375 ml/kg)], pharmacokinetic analyses (the blood sample was harvested before injection, 5 min, 10 min, 20 min, 40 min, 1 h, 2 h, 4 h, and 8 h after injection in peripheral vein sclerosis experiment), peripheral artery embolization [animals were divided into the following 5 groups (n = 3): NC (saline, 0.250 ml/kg), positive control (EtOH, 0.250 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg)], kidney transcatheter arterial embolization [animals were divided into the following 4 groups (n = 3): positive control (EtOH, 0.250 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg); each healthy kidney was injected with saline as negative control], and biosafety evaluations [animals were divided into the following 5 groups (n = 3): NC (0.250 ml/kg), high-dose EtOH (0.375 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg)]. Then, a prospective cohort study involving 6 patients with peripheral venous malformations (VMs) is performed to explore the clinical safety and effectiveness of REI. From Jun 1, 2023 to August 31, 2023, 6 patients [age: (33.3 ± 17.2) years] with lingual VMs received sclerotherapy of REI and 2-month follow-up. Adverse events and serious adverse events were evaluated, whereas the efficacy of REI was determined by both the traceability of the REI under DSA throughout the entire injection and the therapeutic effect 2 months after a single injection. RESULTS: The REI contains 81.4% ethanol (v/v) and 111.3 mg/ml iodine, which can be traced throughout the injection in the animals and patients. The REI also exerts a similar effect as EtOH on peripheral venous sclerosis, peripheral arterial embolization, and renal embolization. Furthermore, the REI can be metabolized at a similar rate compared to EtOH and Ultravist® and did not cause injury to the animals' heart, liver, spleen, lungs, kidneys and brain. No REI-related adverse effects have occurred during sclerotherapy of VMs, and 4/6 patients (66.7%) have achieved complete response at follow-up. CONCLUSION: In conclusion, REI is safe, exerts therapeutic effects, and compensates for the radiolucency of EtOH in treating VMs. TRIAL REGISTRATION: The clinical trial was registered as No. ChiCTR2300071751 on May 24 2023.

Epigenetic regulation of VENTXP1 suppresses tumor proliferation via miR-205-5p/ANKRD2/NF-kB signaling in head and neck squamous cell carcinoma.

An increasing number of studies have shown that long noncoding RNAs (lncRNAs) play important roles in tumor development and progression. However, their involvement in head and neck squamous cell carcinoma (HNSCC) remains largely unknown. Epigenetic regulation is one major mechanism utilized by cancer cells to control lncRNA expression. We identified that lncRNA VENTXP1 was epigenetically silenced in multiple cancer types, and its lower expression was correlated with poorer survival in HNSCC patients. Through in silico analysis and experimental validation, we identified miR-205-5p and its direct interacting partner of VENTXP1, which regulates HNSCC cell proliferation and tumorigenicity. Using RNA-seq and differential gene expression analysis, we further identified ANKRD2 as a miR-205-5p target, which plays an essential role in modulating NF-kB signaling. These findings suggest that VENTXP1 inhibits tumor growth via suppressing miR-205-5p/ANKRD2-mediated NF-kB signaling in HNSCC. Thus, pharmaceutical targeting of DNA methylation to restore VENTXP1 expression might constitute a therapeutic strategy for HNSCC.

Local suture ligation-assisted percutaneous sclerotherapy for Kasabach-Merritt phenomenon-associated kaposiform haemangioendothelioma.

Kaposiform haemangioendotheliomas (KHEs) complicated by the Kasabach-Merritt phenomenon (KMP) are rare and severe neoplastic lesions often associated with locally aggressive disease, consumption coagulopathy and high mortality rates. Current regimens have yet to achieve a satisfactory therapeutic effect. Thus, an effective and minimally invasive approach for treating complex KHE/KMP cases is necessary for clinical management. The present case series describes patients with KHE/KMP who underwent local suture ligation-assisted percutaneous sclerotherapy to minimise surgical trauma and ensure effective treatment. Between September 2015 and September 2017, 3 consecutive patients with KHE/KMP underwent staged local suture ligation-assisted percutaneous sclerotherapy. Of these patients, 2 presented with medical histories of corticosteroid treatment with unsatisfactory outcomes. The patients underwent a stepwise synthetic serial therapy programme consisting of percutaneous sclerotherapy and adjunctive pharmacotherapy accompanied by a suture ligation procedure. Clinical, radiological, pathological and laboratory data were analysed to evaluate the outcomes of the therapy. All patients were successfully managed with the proposed procedure. Significant relief of clinical symptoms and improvements in haematological indicators were achieved. No recurrence or complications were observed during regular follow-up (4, 19 and 28 months). In conclusion, local suture ligation-assisted percutaneous sclerotherapy was demonstrated to be a safe and effective treatment for KHE/KMP, being minimally invasive, involving simple manipulation and providing a clear treatment benefit in certain cases. Further studies involving larger sample sizes are required to thoroughly evaluate the procedure, which can potentially be used as a novel therapeutic option for KHE/KMP treatment.

A Fluorogenic Probe for Ultrafast and Reversible Detection of Formaldehyde in Neurovascular Tissues.

Formaldehyde (FA) is endogenously produced in live systems and has been implicated in a diverse array of pathophysiological processes. To disentangle the detailed molecular mechanisms of FA biology, a reliable method for monitoring FA changes in live cells would be indispensable. Although there have been several fluorescent probes reported to detect FA, most are limited by the slow detection kinetics and the intrinsic disadvantage of detecting FA in an irreversible manner which may disturb endogenous FA homeostasis. Herein we developed a coumarin-hydrazonate based fluorogenic probe (PFM) based on a finely-tailored stereoelectronic effect. PFM could respond to FA swiftly and reversibly. This, together with its desirable specificity and sensitivity, endows us to track endogenous FA in live neurovascular cells with excellent temporal and spatial resolution. Further study in the brain tissue imaging showed the first direct observation of aberrant FA accumulation in cortex and hippocampus of Alzheimer's mouse model, indicating the potential of PFM as a diagnostic tool.

Percutaneous sclerotherapy with absolute alcohol to treat aneurysmal bone cyst of the frontal bone.

Aneurysmal bone cysts (ABCs) rarely occur in the cranial bone. Surgical resection can lead to bone defects, deformities, functional abnormalities, and so on. This article describes a frontal ABC in a 73-year-old man who has a rapidly increasing swelling in the frontal bone preceded by an accidental trauma. In this case, we use percutaneous sclerotherapy with absolute alcohol under the guidance of fluoroscopy to treat the ABC instead of traditional surgical resection. When analyzed the follow-up imaging, bone reconstruction happened after using absolute alcohol. It is a feasible alternative treatment for ABC arising from the cranial bone.

A second polymorph of catena-poly[[(1,10-phenanthroline-κN,N')copper(II)]-di-µ-thio-cyanato-κN:S;κS:N].

In the title coordination polymer, [Cu(NCS)(2)(C(12)H(8)N(2))](n), the Cu(II) atom is situated on a twofold rotation axis and is coordinated by two N atoms from the bidentate 1,10-phenanthroline ligand and four thio-cyanate groups to confer a CuN(4)S(2) octa-hedral geometry and resulting in a layer structure extending parallel to (100).

A new sesquiterpene with a novel 1ß, 8ß-oxygen bridge from Heteropappus altaicus (willd.) Novopokr.

A new guaiane-type sesquiterpene, 4α,7ß-dihydroxy-10ßH-guai-5-en-1ß,8ß-endoxide (1), was isolated from Heteropappus altaicus (Compositea). The structure of compound 1, which contains exhibited a rare 1,8-oxide bridge, was established on the basis of spectroscopic data.

Two new eremophilenolides from Ligularia lapathifolia.

From the roots of Ligularia lapathifolia two new eremophilane-type sesquiterpenes have been isolated. Their structures were established as 3beta-angeloyloxy-8beta-hydroxy-6alpha,15beta-epoxy-eremophil-7(11)-en-12,8alpha-olide (1) and 8betaH-eremophil-3,7(11)-dien-12,8alpha (15,6alpha)-diolide (2) by spectroscopic methods including 2D NMR experiments.

Sesquiterpenes, nortriterpenes and other constituents from Ligularia tongolensis.

Two new eremophilane-type sesquiterpenes, 3beta-(2'-methylbutanoyloxy)-8betaH-eremophil-7(11)-ene-12,8alpha-(14,6alpha)-diolide (1) and 8betaH-eremophil-3,7(11)-diene-12,8alpha(14,6alpha)-diolide (2), and two new norursane-type triterpenes, 2alpha,3beta,19alpha-trihydroxy-28-norurs-12-ene (7) and 2alpha,3alpha,19alpha-trihydroxy-28-norurs-12-ene (8), were isolated from the roots of Ligularia tongolensis, together with nine known compounds. The structures of the new compounds were elucidated by spectroscopic methods.

New sesquiterpenes from Sonchus transcaspicus.

Four new eudesmanolides were isolated from the whole plant of Sonchus transcaspicus and their structures were elucidated by means of spectroscopic methods, including 2D-NMR (1H-1H COSY, HMQC, HMBC and NOESY) and NOEDS (NOE difference spectra) as 1beta-O-beta-D-glucopyranosyl-5alpha,6beta H-eudesma-3-en-12,6alpha-olide (1), 1beta-O-beta-D-glucopyranosyl-15-O-( p-hydroxyphenylacetyl)-5alpha,6beta H-eudesma-3,11(13)-dien-12,6alpha-olide (2), 1beta-O-beta-D-glucopyranosyl-(6'-O-p-hydroxyphenyl acetate)-15-O-(p-hydroxyphenylacetyl)-5alpha,6beta H-eudesma-3,11(13)-dien-12,6alpha-olide (3) and 1beta-hydroxy-15-O-(p-methoxyphenylacetyl)-5alpha,6beta H-eudesma-3,11(13)-dien-12,6alpha-olide (4). Compounds 1, 2 and 3 showed antibacterial activity against Escherichia coli and Staphylococcus aureus cells. Compounds 2 and 3 were evaluated for their in vitro cytotoxic activity against cultured SMMC-7721 (human hepatoma), HELA (human cervical carcinoma) and B-16 (murine melanoma) cells. The IC50 values for 2 were 108.0, 161.1 and 203.0 microM and those for 3 were 74.1, 117.3 and 135.0 microM, respectively. The structure-activity relationship is discussed.

New sesquiterpenes from Erigeron annus.

Four new and five known eudesmane-type sesquiterpenes were isolated from the aerial parts of Erigeron annus. The structures of these new compounds were elucidated by spectral means, including 2D-NMR analysis, to be 1 beta,4 beta-dihydroxyeudesman-11-ene; 1 beta,7 alpha-dihydroxyeudesman-4(15)-ene; (1 R,5 S,6 S,7 S,10 R)-1 beta, 6 alpha-dihydroxyeudesman-4-one and 1 beta- D-glucopyranosyloxy-6 alpha-hydroxyeudesman-4(15)-ene. In addition, a chemical transformation of a known compound 1 beta,6 alpha-dihydroxy-eudesman-4 (15)-ene was carried out and the derivative 1beta,6alpha-dihydroxy-4beta(15)-epoxyeudesmane was obtained. Some of the compounds were evaluated for their in vitro antitumor activities.

Sesquiterpenes, lignans and other constituents from Saussurea macrota.

From the methanol extract of the whole plant of Saussurea macrota Franch, 21 compounds were isolated. Their structures were elucidated by spectroscopic methods and X-ray crystallography. Two of them are new: 3alpha-hydroxy-11alphaH-guaia-4(15),10(14)-diene-12,6alpha-olide (1) and 7'-hydroxyiso-lappaol A (11). Compound 2 is reported as a natural compound for the first time. In addition, the compounds 12 and 13 showed significant antitumor activity against Bel-7402 and HO-8910 cells. Some of the compounds exhibited weak antibacterial activity against Staphylococcus aureus, Bacillus subtilis and Escherichia coli.

Sesquiterpenes and other constituents from Cacalia deltophylla.

From the whole plant of Cacalia deltophylla (Maxim) Mattf, together with twelve known compounds (3-14), a new furanoeremophilane-type sesquiterpene named deltocacalone (1), and a new norsesquiterpene named deltonorcacalol (2) were isolated. Their structures were elucidated by spectroscopic methods including 2D-NMR techniques.

Sesquiterpenes from roots of Lingularia veitchiana.

Together with seven known sesquiterpenes, a new guaiane, a new furanoeremophilane, and a new eudesmane were isolated from the roots of Ligularia veitchiana. Their structures were elucidated by spectroscopic methods. The bioactivities of three known guaiane sesquiterpenes were determined.