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Oleocanthal and oleacein are the two major secoiridoids exclusively present in extra virgin olive oil (EVOO). Both compounds exert important pharmacological activities, including anti-inflammatory, anti-tumoral, neuro- and cardiovascular protective effects. Due to their enormous potential as possible drugs the extraction of these two bioactive natural products from EVOO has been extensively investigated in the last years and is generally supported by the use of organic chemistry. It is quite difficult to produce large quantities of these two compounds, either by organic solvent extraction and purification or by chemical synthesis, and furthermore organic processes such as cleaning, defatting, and extraction of EVOO pose a threat to the environment and are potentially harmful to workers. In this work we set up a novel aqueous extraction and isolation method from EVOO by transforming oleocanthal and oleacein into two water-soluble sulfonated products. The two derived compounds, here named thiocanthal and thiocanthol, were isolated by a two-step organic free chromatographic strategy, chemically characterized, and evaluated for their inhibitory activity on cyclooxygenase (COX). The results demonstrate that thiocanthal and thiocanthol possess anti-inflammatory effect, which is comparable to their precursors and higher than the well-known non-steroidal anti-inflammatory drug ibuprofen. Computational docking studies were performed to obtain and analyse putative models of the interaction of thiocanthal and thiocanthol with COX-1 and COX-2 binding sites. Predicted binding energy values suggested that both compounds might preferentially bind COX-2, which may have a significant pharmacological impact. Therefore, thiocanthal and thiocanthol, obtained by this novel green process, are extremely interesting both as new bioactive compounds per se and as lead compounds for the development of novel non-steroidal anti-inflammatory drugs (NSAIDs)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The optical purity of cannabichromene (CBC, 1a ) is affected by the matrix in which it is generated by thermolysis from its native carboxylated form (cannabichromenic acid, CBCA, 1b ). Thus, thermolysis at 130 °C in planta caused a marked decrease of the enantiomeric excess (ee), while, under the same conditions, only a modest decrease of optical purity was observed when thermolysis was carried out in extracto . To rationalize these puzzling observations, the kinetics of thermal (100 °C) racemization of enantiopure cannabichromene ( 1a ) was evaluated by enantioselective ultrahigh performance liquid chromatography in solvents (decalin and isopropyl alcohol, neat and acidified with TFA) and surfaces (native and silanized borosilicate glass) of complementary polarity. Optical stability was more than halved in isopropanol compared to decalin ( t 1/2 50 h vs 135 h), but acidification had no effect on racemization. However, contact with a solid surface dramatically accelerated the process, with a t 1/2 of only 6 h on both glass surfaces. The overall extent of racemization of enantiopure CBC ( 1a ) was compared under conditions commonly used for decarboxylation (heating at 130 °C) between a decalin solution and a thin film on three different surfaces (native and silanized borosilicate glass and powdered blank cannabis biomass). In line with the kinetic data, a significant erosion of enantiopurity was observed on all solid surfaces compared to the solution. These observations suggest that discrepancies in the reported enantiomeric purity of natural CBC could be not only of biogenetic derivation but also be associated with the decarboxylation protocol of cannabichromenic acid ( 1b ). These findings, while relevant for the exploitation of the bioactivity of natural CBC for human health, should also prompt the adoption of a standardized decarboxylation protocol for the studies on the configurational status of CBC ( 1a ) in cannabis and, in general, of cannabinochromanoids in nature.

The existence of slow adsorption-desorption kinetics in chiral liquid chromatography is common knowledge. This may significantly contribute to worsening the efficiency and kinetic performance of a chromatographic run, especially when high flow rates are employed. Many attempts and protocols have been proposed to access this term, the so-called c ads , but they are based on different (theoretical) assumptions. As a consequence, no official method is available for the estimation of the adsorption-desorption kinetics term. In this work, a novel approach to access c ads is presented. This procedure combines experimental results obtained with kinetic and thermodynamic measurements. The investigations have been performed on two zwitterionic teicoplanin chiral stationary phases (CSPs) based on 1.9 μ m fully porous and 2.0 μ m superficially porous particles (FPPs and SPPs), using Z-D,L-Methionine as probe molecule. Kinetic studies have been performed through the combination of both stop-flow and dynamic measurements, while adsorption isotherms have been calculated through Inverse Method. This study has confirmed that, on both particle formats, analyte diffusion on the surface of the particle is negligible, meaning that adsorption is localized, and it has been demonstrated that adsorption-desorption kinetics is strongly dependent on particle geometry and, in particular, on the loading of chiral selector. These findings are fundamental not only to unravel novel aspects of the complex enantiorecognition mechanism but also to optimize the employment of CSPs for ultra-fast and preparative applications., (© 2024. The Author(s).)

The biopharmaceutical industry faces the challenge of efficiently characterising impurity profiles of therapeutical peptides, also due to their complex polar and ionisable attributes. This research explores the potential of advanced chromatographic techniques to address this challenge. The study compares dynamic electrostatic repulsion reversed phase (d-ERRP) to its counterparts (static ERRP and ion pair reversed phase IP-RP) in analysing Icatibant and its elusive epimeric impurity, [L-Arg] 1 -Icatibant and highlights its exceptional capabilities in generating symmetric peaks, mitigating the common tailing phenomenon, and serving as a steadfast guardian of column longevity. The result highlights d-ERRP as a pioneering tool in the domain of liquid chromatography, fostering its role as a reference technique for the analysis of therapeutic peptides., Competing Interests: Declaration of Competing Interest There are no conflicts to declare., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

In this study, we aimed to make enantioselective chromatography more sustainable, more sensitive, and compatible with aqueous formulations analysis and ESI-MS. To achieve this, we examined the effects of transitioning from normal-phase chromatography (which uses hydrocarbon-based solvents) to reversed-phase chromatography (using mobile phases based on water) using broad-spectrum Whelk-O1 columns as a critical study. For the first time, we holistically compared the thermodynamics and kinetics of the two elution modes in order to answer the question of whether same-column chemistry can effectively separate the compounds even in reversed-phase mode and found, unexpectedly, that reversed-phase chromatography using acetonitrile as the organic modifier was competitive from a kinetic standpoint. We also evaluated the effectiveness of three organic modifiers simultaneously on a sample of 11 molecules already resolved in NP conditions with different resolutions and achieved a resolution value of 1.5 for 91% and a resolution value of 2 for 82% of cases. Finally, we separated three racemates (within a k factor of 9) using only 480 µL of solvent per chromatographic run on a millibore column of 1 mm I.D., demonstrating that our approach allows for greener chromatographic separations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The retention behavior of small molecules and N-protected amino acids on a zwitterionic teicoplanin chiral stationary phase (CSP), prepared on superficially porous particles (SPPs) of 2.0 μm particle diameter, has shown that efficiency and enantioselectivity, and so enantioresolution, dramatically change depending on the employed organic modifier. In particular, it was found that while methanol permits the boost of enantioselectivity and resolution of the amino acids, at the cost of efficiency, acetonitrile allows for the ability to reach extraordinary efficiency even at high flow rates (with reduced plate height <2 and up to 300,000 plates/m at the optimum flow rate). To understand these features, an approach based on the investigation of mass transfer through the CSP, the estimation of the binding constants of amino acids on the CSP, and the assessment of compositional properties of the interfacial region between bulk mobile phase and solid surface has been adopted.

Cannabichromene (CBC, 1a ) occurs in Cannabis ( Cannabis sativa ) as a scalemate having a composition that is strain-dependent in terms of both enantiomeric excess and enantiomeric dominance. In the present work, the chirality of CBC ( 1a ), a noncrystalline compound, was shown not to be significantly affected by standard conditions of isolation and purification, and enantiomeric self-disproportionation effects were minimized by carrying out the chiral analysis on crude fractions rather than on purified products. A genetic basis for the different enantiomeric state of CBC in Cannabis therefore seems to exist, implying that the chirality status of natural CBC ( 1a ) in the plant is associated with the differential expression of CBCA-synthase isoforms and/or of associated directing proteins with antipodal enantiospecificity. The biological profile of both enantiomers of CBC should therefore be investigated independently to assess the contribution of this compound to the activity of Cannabis preparations.

PURPOSE Renal artery aneurysms (RAAs) are rare in the general population, although the true incidence and natural history remain elusive. Conventional endovascular therapies such as coil embolization or covered stent graft may cause sidebranches occlusion, leading to organ infarction. Flow-diverters (FD) have been firstly designed to treat cerebrovascular aneurysms, but their use may be useful to treat complex RAAs presenting sidebraches arising from aneurysmal sac. To evaluate mid-term follow-up (FUP) safety and efficacy of FD during treatment of complex RAAs. METHODS Between November 2019 and April 2020, 7 RAAs were identified in 7 patients (4 men, 3 women; age range 55-82 years; median 67 years) and treated by FD. Procedural details, complications, morbidity and mortality, aneurysm occlusion and segmental artery patency were retrospectively reviewed. Twelve months computed tomography angiography (CTA) FUP was evaluated for all cases. RESULT Deployment of FD was successful in all cases. One intraprocedural technical complication was encountered with one FD felt down into aneurism sac which requiring additional telescopic stenting. One case at 3 months CTA FUP presented same complication, requiring same rescue technique. At 12 months CTA FUP 5 cases of size shrinkage and 2 cases of stable size were documented. No rescue surgery or major intraprocedural or mid-term FUP complication was seen. CONCLUSION Complex RAAs with two or more sidebranches can be safely treated by FD. FD efficacy for RAA needs a further validation at long term FUP by additional large prospective studies.

Cells with latent stem ability can contribute to mammalian tissue regeneration after damage. Whether the central nervous system (CNS) harbors such cells remains controversial. Here, we report that DNGR-1 lineage tracing in mice identifies an ependymal cell subset, wherein resides latent regenerative potential. We demonstrate that DNGR-1-lineage-traced ependymal cells arise early in embryogenesis (E11.5) and subsequently spread across the lining of cerebrospinal fluid (CSF)-filled compartments to form a contiguous sheet from the brain to the end of the spinal cord. In the steady state, these DNGR-1-traced cells are quiescent, committed to their ependymal cell fate, and do not contribute to neuronal or glial lineages. However, trans-differentiation can be induced in adult mice by CNS injury or in vitro by culture with suitable factors. Our findings highlight previously unappreciated ependymal cell heterogeneity and identify across the entire CNS an ependymal cell subset wherein resides damage-responsive neural stem cell potential., Competing Interests: Declaration of interests C.R.S. is a founder of Adendra Therapeutics and owns stock options and/or is a paid consultant for Adendra Therapeutics, Bicara Therapeutics, Montis Biosciences, Bicycle Therapeutics, Genor Biopharma, and Sosei Heptares, all unrelated to this work. C.R.S. also has an additional appointment as Visiting Professor in the Faculty of Medicine at Imperial College London and holds honorary professorships at University College London and King’s College London., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

A novel zwitterionic-teicoplanin chiral stationary phase (CSP), based on superficially porous particles (SPPs) of 2.7 µm particle diameter and 160 Å pore size, has been prepared and evaluated towards the enantioseparation of important classes of compounds, including chiral drugs, pesticides, and N-derivatized amino acids. The comparison with two analogous CSPs prepared on SPPs with 2.7 and 2.0 µm particle diameter and 90 Å pore size has revealed that the use of large-pore particles allows to dramatically improve both the enantioselectivity and the resolution-per-analysis-time, at the point that the column prepared with the new CSP outperformed the one packed with the finest particles. On the novel wide-pore CSP, the separation of fifteen racemates of pratical importance was significantly improved in terms of both enantioselectivity and resolution-per-analysis time-compared to the CSPs based on SPPs with smaller pores (90 Å). Such a CSP would be suitable for very fast enantioseparations allowing the saving of solvent for greener high-efficiency/high-throughput applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Modification of surface silanols is a topic of interest in the preparation of organo-functionalized silica particles. Herein, two novel contributions, mainly focused on separation science, were presented: i) the horizontal polymerization on silica surface by using the vinyl-triacetoxy silane and ii) a preparation of cysteine-based stationary phase via photo-click thiol-ene coupling. In the first derivatization step, the vinyl-triacetoxy silane was employed instead of conventional trichloro vinyl one. The one-step synthetic procedure needed imidazole as an activating agent in addition to the silica hydration. Modified silica particles offer a high loading of vinyl fragments and an extensive passivation of silanols such as to not require a subsequent end-capping procedure. The structural morphology of media was deeper characterized by combining infrared spectroscopy, solid-state nuclear magnetic resonance, and elemental analysis. A first application, the photo-click cysteine-based material was prepared by photo-click reaction and the stationary phase was employed in the separation of some conventional targets by hydrophilic interaction chromatography., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: To investigate the outcomes of patients with calcific lesions in the common femoral artery undergoing endovascular procedures with atherectomy device and scoring balloon angioplasty combined with treatment of steno-occlusive disease of the remaining arterial districts of the lower limb., Methods: Between January 2015 and December 2018, 11 diabetic patients at high risk for "major amputation", with calcific lesions of the common femoral artery and ischemic ulcers requiring endovascular treatment were retrospectively evaluated. Technical success was defined as revascularization of the common femoral artery with a residual stenosis lower than 30%. Primary endpoints were an immediate increase of perilesional transcutaneous oxygen pressure (TCPO 2 ) > 40 mmHg, ulcerative lesions improvement up to healing or skin flaps re-epithelialization after minor amputation, limb rescue with rejected major amputation, and resolution of rest pain if present., Results: The success rate of the revascularization procedures was 100%. No patient underwent surgical conversion. One case of peri-operative bleeding at the brachial access site was observed. There were no cases of arterial dissection or undesired distal embolization. The average baseline value of perilesional TCPO 2 was 21.8 ± 9.2 mmHg. The mean TCPO 2 value was 57.4 ± 7.2 mmHg three days after the procedure ( P < 0.05 ), and 51.2 ± 9.8 mmHg 15 days after ( P < 0.05 ). Minor amputations were performed in five patients with advanced ulcerative lesions. No major amputations were performed in the follow-up period. At 14 months follow-up, one patient developed new occlusion of the CFA for extension from the external iliac artery and underwent a new endovascular procedure. We observed an overall primary patency rate of 91% and a primary assisted patency rate of 100% in our 18-month follow-up., Conclusions: Endovascular approach for severely calcified atherosclerotic lesions of the common femoral artery seems to represent a valid therapeutic option associated with promising results in terms of clinical outcome and low complication rates.

Aim: To report the multicenter retrospective experience on combination of balloon-occluded MWA(b-MWA) followed by balloon-occluded TACE(b-TACE) in patients with liver malignancies > 3 cm, focusing on appearance and volume of necrotic area, safety profile and oncological results., Materials and Methods: Twenty-three patients with liver primary malignancies (hepatocellular carcinoma,HCC = 18; intrahepatic cholangiocarcinoma,iCC = 2) and metastasis (colorectal cancer metastasis = 1;sarcoma metastasis = 1;breast metastasis = 1) were treated. Maximum mean diameter of lesions was 4.4 cm (± 1 cm). Treatments were performed using a single-step approach:b-MWA was performed after balloon-microcatheter inflation, followed by b-TACE (with epirubicin or irinotecan). Necrotic area shape and discrepancy with the expected volume of necrosis suggested by vendor's ablation chart were assessed at post-procedural CT. Complications were categorized according to CIRSE classification. Oncological results at 1 and 3-6 months were evaluated using m-RECIST(HCC) and RECISTv1.1(metastasis/iCC)., Results: Mean volume of necrotic area was 75 cm 3 (± 36). Discrepancy with vendor chart consisted in a medium percentage of volumetric incrementation of necrotic area of 103.2% (± 99.8). Non-spherical shape was observed in 22/23 patients (95.7%). No complications occurred; Post-embolization syndrome occurred in 12/23patients. Complete response and partial response were, respectively, 91, 3% (21/23) and 8.7% (2/23) at 1 month, 85.7% (18/21) and 9.5% (2/21) at 3-6 months. Progression of disease was 4.7% (1/21) at 3-6 months for extra-hepatic progression. Among partial responders, average percentage of tumor volume debulking was 78.8% (± 9.8%)., Conclusion: b-MWA followed by b-TACE in a single-step procedure led to larger necrotic areas than the proposed by vendors ablation chart, non-spherical in shape and corresponded to the vascular segment occluded during ablation. This permitted to safely achieve promising oncological results in patients with > 3 cm tumors., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

trans -Resveratrol is a natural bioactive compound with well-recognized health promoting effects. When exposed to UV light, this compound can undergo a photochemically induced trans / cis isomerization and a 6π electrochemical cyclization with the subsequent formation of 2,4,6-trihydroxyphenanthrene (THP). THP is a potentially harmful compound which can exert genotoxic effects. In this work we improved the chromatographic separation and determination of the two resveratrol isomers and of THP by using a non-commercial pentafluorophenyl stationary phase. We assessed the effect of natural deep eutectic solvents (NaDES) as possible photo-protective agents by evaluating cis -resveratrol isomer and THP formation under different UV-light exposure conditions with the aim of enhancing resveratrol photostability and inhibiting THP production. Our results demonstrate a marked photoprotective effect exerted by glycerol-containing NaDES, and in particular by proline/glycerol NaDES, which exerts a strong inhibitory effect on the photochemical isomerization of resveratrol and significantly limits the formation of the toxic derivative THP. Considering the presence of resveratrol in various commercial products, these results are of note in view of the potential genotoxic risk associated with its photochemical degradation products and in view of the need for the development of green, eco-sustainable and biocompatible resveratrol photo-stable formulations.

Enantioselective chromatography has been the preferred technique for the determination of enantiomeric excess across academia and industry. Although sequential multicolumn enantioselective supercritical fluid chromatography screenings are widespread, access to automated ultra-high-performance liquid chromatography (UHPLC) platforms using state-of-the-art small particle size chiral stationary phases (CSPs) is an underdeveloped area. Herein, we introduce a multicolumn UHPLC screening workflow capable of combining 14 columns (packed with sub-2 μm fully porous and sub-3 μm superficially porous particles) with nine mobile phase eluent choices. This automated setup operates under a vast selection of reversed-phase liquid chromatography, hydrophilic interaction liquid chromatography, polar-organic mode, and polar-ionic mode conditions with minimal manual intervention and high success rate. Examples of highly efficient enantioseparations are illustrated from the integration of chiral screening conditions and computer-assisted modeling. Furthermore, we describe the nuances of in silico method development for chiral separations via second-degree polynomial regression fit using LC simulator (ACD/Labs) software. The retention models were found to be very accurate for chiral resolution of single and multicomponent mixtures of enantiomeric species across different types of CSPs, with differences between experimental and simulated retention times of less than 0.5%. Finally, we illustrate how this approach lays the foundation for a streamlined development of ultrafast enantioseparations applied to high-throughput enantiopurity analysis and its use in the second dimension of two-dimensional liquid chromatography experiments.

Aim: To evaluate the efficacy of intravascular ultrasound (IVUS) in transjugular intrahepatic portosystemic shunt (TIPS) revision associated with phlebography and invasive pressure measurement in patients with clinical or radiological signs of TIPS malfunction., Background: Four patients underwent TIPS revision between February and August 2021. Right internal jugular vein access was achieved under ultrasonographic guidance, a catheter was advanced to achieve the Inferior Vena Cava (IVC) and afterward the Portal vein through the TIPS. Once the Portal vein was achieved, a phlebography was performed, followed by invasive pressure measurement and IVUS exam over the guidewire. Based on the combination of phlebography, invasive pressure measurement, and IVUS evaluations, TIPS dysfunction was treated either with angioplasty or stent apposition., Case Description: In all patients, we obtained the reduction of porto-systemic gradient. In three patients, angioplasty with a 10 mm diameter balloon catheter was performed. Anticoagulation therapy was added to one patient. In one patient, the Viatorr's proximal extremity in the suprahepatic vein wall was dislocated, so it was lengthened with a "Viabahn" covered stent. None of the patients developed hepatic encephalopathy after both TIPS placement and TIPS revision. No complications related to the procedure were observed during the follow-up. Clinical improvement in the immediate follow-up period was observed in all patients. In two patients, the abdominal ascites resolved. In another one, the abdominal pain disappeared, and a reduction of the longitudinal spleen diameter was recorded at 3 months follow-up., Conclusion: The use of IVUS allowed us to correctly visualize the organic cause of TIPS malfunction and to obtain direct visualization of the results of endovascular treatment., How to Cite This Article: Morosetti D, Lenci I, Argirò R, et al . Use of Intravascular Ultrasound to Improve Diagnosis and Treatment of Transjugular Intrahepatic Portosystemic Shunt Dysfunction in Patients in the Long-term Follow-up. Euroasian J Hepato-Gastroenterol 2022;12(1):50-56., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2022; Jaypee Brothers Medical Publishers (P) Ltd.)

The cis -stereoisomers of Δ 9 -THC [(-)- 3 and (+)- 3 ] were identified and quantified in a series of low-THC-containing varieties of Cannabis sativa registered in Europe as fiber hemp and in research accessions of cannabis. While Δ 9 - cis -THC ( 3 ) occurs in cannabis fiber hemp in the concentration range of (-)-Δ 9 - trans -THC [(-)- 1 ], it was undetectable in a sample of high-THC-containing medicinal cannabis. Natural Δ 9 - cis -THC ( 3 ) is scalemic (ca. 80-90% enantiomeric purity), and the absolute configuration of the major enantiomer was established as 6a S ,10a R [(-)- 3 ] by chiral chromatographic comparison with a sample available by asymmetric synthesis. The major enantiomer, (-)-Δ 9 - cis -THC [(-)- 3 ], was characterized as a partial cannabinoid agonist in vitro and elicited a full tetrad response in mice at 50 mg/kg doses. The current legal discrimination between narcotic and non-narcotic cannabis varieties centers on the contents of "Δ 9 -THC and isomers" and needs therefore revision, or at least a more specific wording, to account for the presence of Δ 9 - cis -THCs [(+)- 3 and (-)- 3 ] in cannabis fiber hemp varieties.