Mihai Adrian Socaciu

Background: Preoperative CT is part of the routine diagnostic work-up for colorectal cancer (CRC), and CT-based biomarkers have been linked to oncological and surgical outcomes in CRC patients. This review aims to evaluate the association between preoperative CT-derived vascular disease markers (calcification and stenosis) and postoperative outcomes after curative CRC resection with anastomosis. Methods: Following PRISMA, we conducted a systematic review and meta-analysis of studies identified from MEDLINE/PubMed, Embase, Web of Science Core Collection and Google Scholar from inception until 1st of January 2026, with the protocol registered in PROSPERO (CRD420251248044). Eligible studies examined CT-derived abdominal vascular disease markers in CRC patients treated with curative resection and anastomosis and reported postoperative outcomes (anastomotic leakage (AL) grade C, major morbidity, and mortality). Risk of bias was assessed using the Newcastle–Ottawa Scale. We pooled odds ratios using random-effects models when ≥3 studies reported comparable exposure–outcome comparisons. Results: Fourteen studies (6712 participants) were included, and 12 contributed to quantitative synthesis. Higher calcification burden was associated with increased odds of any AL (OR 3.08, 95% CI 2.09–4.54; k = 11; n = 5005) and severe/grade C AL (OR 2.68, 95% CI 1.03–6.97; k = 3; n = 3418). Evidence for major morbidity was imprecise (OR 1.99, 95% CI 0.86–4.59; k = 3; n = 841), and data for mesenteric stenosis outcomes and mortality were limited. Sensitivity analyses indicate attenuation without loss of significance after trim-and-fill (adjusted OR 2.39) and that non-ROC cut points yield a smaller effect size (OR 2.42). Conclusions: CT-derived vascular disease markers are associated with higher odds of AL after CRC surgery. Prospective studies should standardize methods and test clinical utility.

Background and Clinical Significance: Deficiency of Adenosine Deaminase 2 (DADA2) is a rare monogenic vasculopathy characterised by systemic inflammatory and immunodeficiency features. Although neurological and haematological manifestations are well-documented, hepatic vascular involvement remains underappreciated. This report aims to describe the clinical and imaging characteristics of hepatic vascular involvement in a patient with DADA2 and to illustrate the evolution of hepatic lesions during long-term Etanercept therapy. In addition, we provide a synthesis of the available evidence on hepatic manifestations in DADA2, emphasising vascular pathology, clinical presentation, and therapeutic implications. Case Presentation: We describe a girl with early-onset DADA2 presenting with recurrent systemic inflammation, hypogammaglobulinaemia, vasculopathy, and two childhood strokes, followed by the development of multiple FNH-like hepatic nodules on CEUS and MRI with persistently elevated GGT. Genetic testing confirmed biallelic ADA2 mutations, and treatment with Etanercept led to sustained clinical stabilisation and marked regression of liver lesions over a nine-year follow-up period. Her older sister, carrying the same mutations, showed a milder phenotype without hepatic involvement but experienced a mesenteric vascular event. Conclusions: Large regenerative nodules with an FNH-like appearance on CEUS or MRI have not been previously reported in this setting. In our patient, Etanercept therapy produced a favourable hepatic response, reflected by a significant reduction in both the number and size of the lesions. Our case contributes to the understanding of liver disease in DADA2 and the influence of imaging and treatment on the hepatic manifestations of the condition.

Due to their complexity, both genotypic and phenotypic, neurodegenerative diseases are one of the main causes of death globally nowadays. Among phytochemicals of high scientific interest, based on experimental studies, pentacyclic triterpenoids (TTs), including mainly betulin, betulinic, and ursolic acid, became targets of scientific research in recent years, especially in terms of their biological activity and pharmacological potential. Due to their anti-inflammatory and antioxidant properties, as well as their involvement in cellular signal transductions, they have been observed to act as anticancer, chemopreventive, and neuroprotective agents. The aim of this review is to update the reader on the diversity, bioavailability, pharmacological properties, and neuroprotective effects of TTs, as biomolecules that can interfere with metabolic mechanisms related to neurodegeneration and restoring of neuronal integrity. Recent data were analyzed, with a particular focus on mechanistic insights related to their neuroprotective effects. Starting with their biosynthetic pathways, bioavailability, and involvement in specific metabolic pathways, their impact on neurological pathology and benefits as natural neuroprotection agents through specific signaling pathways are presented. Furthermore, emphasis will also be put on current challenges and future strategies that could develop TTs into effective compounds for neuroprotection and personalized medicine.

Background: Betulins (betulin, betulinic acid and lupeol) demonstrated antitumor and chemopreventive activity but showed low bioavailability due to their self-aggregation in hydrophilic environments. To overcome these disadvantages, their incorporation into lipid nanoformulations (PEGylated liposomes and Lipid Nanostructured Carriers (NLCs)) has proven to represent a viable solution. Objectives: The purpose of this study is to evaluate the size and incorporation rate of these molecules in nanoformulations, as well as their delivery and metabolic fate (pure betulinic acid versus a standardized extract, TT) relative to Doxorubicin using an in vivo protocol. The investigation extended our previous in vitro investigations towards an in vivo evaluation of antitumor activity, metabolic fate and toxicity in Wistar rats bearing Walker 256 carcinoma tumors over 21 days. Since previous studies used oral or intratumor administration, this exploratory study applied intravenous administration via microbubble-assisted sonoporation, considering its higher relevance for translational studies. Methods: The delivery and metabolic fate of the parent molecules, the identification of their fragments and metabolites using UHPLC-QTOF-ESI⁺MS were investigated, along with the identification of some toxicity biomarkers in rat plasma, tumor tissues and urine. Results: Preferential accumulation of Doxorubicin in tumors was observed compared to betulinic acid and TT components, as well as their persistence in plasma or elimination in urine. Compared to PEGylated liposomes, NLC formulations (especially NLC Doxo) induced a lower survival rate, a decreased bioavailability and increased toxicity by around 20%. Conclusions: These data are a starting point and complement the contrast-enhanced imaging and histology evaluations, which may contribute to the actual knowledge about the in vivo fate of betulins.

Background and Objectives: Liver fibrosis is the key prognostic factor in patients with chronic liver diseases (CLD). Computed tomography (CT) is widely used in clinical practice, but it has limited value in assessing liver fibrosis in precirrhotic stages. Quantitative CT analysis based on radiomics can provide additional information by extracting hidden image patterns, but the optimal approach remains to be determined. The aims of this study were to evaluate automated CT-based radiomic models for predicting biopsy-proven liver fibrosis, to compare different segmentation strategies and organ inclusions approaches, and to assess its performance against vibration-controlled transient elastography (VCTE). We also examined whether these models could predict liver steatosis. Methods: In this retrospective study, 58 patients with biopsy-proven CLD and 9 controls underwent VCTE and contrast-enhanced abdominal CT within three months of biopsy. Radiomic features were extracted from portal-venous-phase images using both two-dimensional (2D) and three-dimensional (3D) segmentations of the liver, spleen, and combined liver–spleen. Multilayer perceptron neural (MLP) networks were trained to predict fibrosis staging (≥F1, ≥F2, ≥F3, and F4) and steatosis grading (≥S1, ≥S2, and S3). Model performance was assessed using area under the receiver operating characteristic curve (AUROC) and accuracy. Results: The 3D radiomic models outperformed 2D models in predicting liver fibrosis stages. In the 3D radiomic model category, the combined 3D liver–spleen model achieved very good to excellent performance (AUROCs 0.974, 0.929, 0.928, and 0.898, respectively, for ≥F1, ≥F2, ≥F3, and F4), with comparable results to VCTE (AUROCs 0.921, 0.957, 0.968, and 0.909, respectively, for ≥F1, ≥F2, ≥F3, and F4). Radiomic models showed poor predictive ability for steatosis grades (AUROCs 0.44–0.69) compared to controlled attenuation parameter (CAP) (AUROCs 0.798–0.917). Conclusions: CT-based radiomic models showed potential for predicting liver fibrosis stage. The 3D model of liver and spleen had the highest performance, comparable to VCTE. This approach could be valuable in clinical settings where elastography is unavailable or inconclusive and for opportunistic screening in patients already undergoing CT for other medical indications. In contrast, portal-venous-phase radiomics lacked predictive value for steatosis assessment. Larger, multicenter studies are required to validate these results.

Background: Liposomes and, more recently, structured nanolipid particles have demonstrated effectiveness as carriers for delivering hydrophilic or lipophilic anticancer agents, enhancing their biocompatibility, bioavailability, and sustained release to target cells. Objective: Herein, four doxorubicin formulations—comprising either the acidic or neutral form—were encapsulated into liposomes (Lipo) or nanostructured lipid carriers (NLCs) and characterized in terms of size, entrapment efficiency, morphology, and effects on two cancer cell lines (melanoma B16-F10 and breast carcinoma Walker 256 cells). Methods and Results: While liposomal formulations containing acidic doxorubicin displayed IC₅₀ values ranging from 1.33 to 0.37 µM, NLC-based formulations, particularly NLC-Doxo@Ac, demonstrated enhanced cytotoxicity with IC₅₀ values as low as 0.58 µM. Neutral Doxorubicin demonstrated lower cytotoxicity in both the nanoformulations and cell lines. Differences were also observed in their internalization patterns, cell-cycle impact, and apoptotic/necrotic effects. Compared to liposomes, NLCs exhibited distinct internalization patterns and induced stronger cell-cycle arrest and necrosis, especially in melanoma cells. Notably, NLC-Doxo@Ac outperformed liposomal counterparts in melanoma cells, while liposomal formulations showed slightly higher efficacy in Walker cells. Early and late apoptosis were more pronounced in Walker cells, whereas necrosis was more prominent in melanoma B16-F10 cells, particularly with the nanolipid formulations. Conclusions: These results correlated positively with cell-cycle measurements, highlighting the potential of NLCs as an alternative to liposomes for the delivery of neutral or acidic doxorubicin, particularly in tumor types that respond poorly to conventional formulations.

Background/Objectives: Pentacyclic triterpenoids, as bioactive phytochemicals, have proven to exhibit significant bioactivity (antioxidant, anti-inflammatory, hypoglycemic, and anticancer) and low cytotoxicity. This study developed convenient methods for extracting and characterizing a birch bark extract enriched in pentacyclic triterpenoids (betulin, betulinic acid, and lupeol) and entrapped in two bioavailable nanoformulations. The performance of ATR-FTIR spectroscopy as a cost-effective and non-destructive method was evaluated comparatively with accurate HPLC-based methods. Methods: The bark extract and pure betulin or betulinic acid were used to obtain PEGylated liposomes and nano lipid carriers (NLCs). Their size was characterized by light scattering diffraction. UV–Vis spectrometry was applied as a preliminary evaluation (1), as well as UHPLC-QTOF-ESI⁺-MS for structure identification (2), ATR-FTIR spectroscopy (for semi-quantitative evaluation) (3), and HPLC-DAD for an accurate quantification of each component, either in the organic solvents or in the nanoformulations (4). Results: The PEGylated liposomes had smaller sizes, and higher entrapment efficiency, significantly correlated between the three analytical methods. The performance of ATR-FTIR spectroscopy was positively correlated with HPLC-DAD data and confirmed the potential of this cheaper and reliable semi-quantitative method to evaluate the entrapment efficiency of TTs in liposome and NLC nanoformulations. Conclusions: The results recommend using liposomal nanoformulations for the entrapment of bioactive terpenoids and their characterization by ATR-FTIR after validation by HPLC-DAD. The ATR-FTIR spectroscopy also offers the possibility of screening in a short time different recipes of nanoformulations as well as their stability and bioavailability, which is useful for investigations in vitro and in vivo, which may confirm their efficacy as therapeutic agents.

Background/Objectives: Pentacyclic triterpenoids are increasingly studied as anticancer agents with many advantages compared to synthetic chemotherapeutics. The aim of this study was to prepare liposomal and nanostructured lipid formulations including a standardized extract of silver birch (Betula pendula) outer bark (TTs) and to evaluate their potential as anticancer agents in vitro, using Melanoma B16-F10 and Walker carcinoma cells. Methods: Appropriate solvents were selected for efficient TTs extraction, and original recipes were used to obtain Pegylated liposomes and nanolipid complexes with entrapped TTs, comparative to pure standards (betulinic acid and doxorubicin) in similar conditions. The composition, morphology, and sizes of all nanoformulations were checked by high-performance liquid chromatography/mass spectrometry, Transmission Electronic Microscopy, and Diffraction Light Scattering. The entrapment efficiency and its impact on cell viability, cell cycle arrest, and apoptosis by flow cytometry was also measured on both cancer cell lines. Conclusions: The standardized TTs, including betulin, lupeol, and betulinic acid, showed good stability and superior activity compared to pure betulinic acid. According to experimental data, TTs showed good entrapment in liposomal and NLC nanoformulations, both delivery systems including natural, biodegradable ingredients and enhanced bioavailability. The apoptosis and necrosis effects were more pronounced for TTs liposomal formulations in both types of cancer cells, with lower cytotoxicity compared to Doxorubicin, and can be correlated with their increased bioavailability.

Background/Objectives: Pentacyclic triterpenoids, as bioactive phytochemicals proved significant bioactivity (antioxidant, anti-inflammatory, hypoglycemic, and anticancer) and low cytotoxicity. This study developed convenient methods for extracting and characterizing a birch bark extract enriched in pentacyclic triterpenoids (betulin betulinic acid and lupeol) and entrapped in two bioavailable nanoformulations. The performance of ATR-FTIR spectroscopy as a cost-effective and non-destructive method was evaluated comparatively with accurate HPLC-based methods. Methods: The bark extract and pure betulin or betulinic acid were used to obtain PEGylated liposomes and Nano Lipid Carriers (NLC). Their size was characterized by light scattering diffraction. UV-VIS spectrometry was applied as a preliminary evaluation (1), the UHPLC-QTOF-ESI+-MS for structure identification (2), the ATR-FTIR spectroscopy (for semi-quantitative evaluation) (3), HPLC-DAD for accurate quantification of each component, either in the organic solvents and in nanoformulations (4). Results: The PEGylated liposomes had smaller sizes, and higher entrapment efficiency, significantly correlated between the three analytical methods. The performance of ATR-FTIR spectroscopy was positively correlated with HPLC-DAD data and confirmed the potential of this cheaper and reliable semi-quantitative method to evaluate the entrapment efficiency of TTs in liposome and NLC nanoformulations. Conclusions: The results recommend using liposomal nanoformulations for entrapment of bioactive terpenoids and their characterization by ATR-FTIR after validation by HPLC-DAD. The ATR-FTIR spectroscopy also offers the possibility of screening in a short time different recipes of nanoformulations as well as their stability and bioavailability, useful for investigations in vitro and in vivo which may confirm their efficacy as therapeutic agents.

Background/Objectives: Pentacyclic Triterpenoids are increasingly studied as anti-cancer agents with many advantages comparative to synthetic chemotherapeutics. The aim of this study was to prepare liposomal and nanostructured lipid formulations including a standardized extract of silver birch (Betula pendula) outer bark (TTs) and to evaluate their potential as anti-cancer agents in vitro, using Melanoma B16-F10 and Walker carcinoma cells. Methods: Appropriate solvents were selected for an efficient TTs extraction, and original recipes were used to obtain Pegylated liposomes and nanolipid complexes with entrapped TTs, comparative to pure standards (betulinic acid and doxorubicin) in similar conditions. The composition, morphology and sizes of all nanoformulations were checked by High Performance Liquid Chromatography/Mass spectrometry, Transmission Electronic Microscopy and Diffraction Light Scattering. The entrapment efficiency and their impact on cell viability, cell cycle arrest and apoptosis by Flow Cytometry was also measured on both cancer cell lines. Conclusions: The standardized TTs showed good stability, synergistic effects of main components and superior comparative to pure betulinic acid. According to experimental data, TTs showed good entrapment in liposomal and NLC nanoformulations, both delivery systems including natural, biodegradable ingredients and enhanced bioavailability. The apoptosis and necrosis effects were more pronounced for TTs liposomal formulations in both types of cancer cells, with lower cytotoxicity comparative to Doxorubicin, and can be correlated with their increased bioavailability.