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Background: The most common cause of coronary artery diseases (CAD) is atherosclerosis. The synergy between percutaneous coronary intervention with TAXUS™ and cardiac surgery (SYNTAX) score was used to assess complex CAD lesions. The renal resistive index (RRI) is a Doppler ultrasound parameter calculated to assess renal haemodynamics. The direct relationship between CAD complexity and RRI was not yet investigated. The aim of our study was to investigate this relationship between RRI and SYNTAX score in stable CAD patients. Methods: This study included 214 patients with stable CAD and subsequent coronary angiography done at our institution. Regarding CAD complexity, these patients were classified into 166 patients with low SYNTAX score (SYNTAX ≤22), and 48 patients with high SYNTAX score (SYNTAX >22). The demographic, laboratory, clinical, echocardiographic data and renal Doppler parameters; including RRI, were recorded. Results: Multivariate logistic regression analysis demonstrated that RRI (odds ratio, OR = 4.440, 95% (confidence interval) CI: 1.418–13.903, p = 0.010) was a novel independent predictor of high SYNTAX score in patients with stable CAD, in addition to other traditional predictors as diabetes mellitus (OR = 4.401, 95% CI: 1.081–17.923, p = 0.04), low-density lipoprotein cholesterol (LDL-C) (OR = 2.957, 95% CI: 1.920–8.995, p = 0.027), multi-vessel CAD (OR = 2.113, 95% CI: 1.241–2.280, p = 0.001) and Gensini score (OR = 6.539, 95% CI: 1.977–21.626, p = 0.002). Receiver operator characteristic curve analysis showed that RRI >0.655 (sensitivity of 80%, specificity of 73.6%) was the best cut-off value for predicting high SYNTAX score. Conclusions: The non-invasively measured RRI is closely associated with high SYNTAX score in stable CAD patients.

Background Renal stones are a prevalent urological disorder with various treatment options, including minimally invasive techniques such as Standard-PCNL (S-PCNL) and Mini-percutaneous nephrolithotomy (M-PCNL). This study aims to compare the efficacy and safety outcomes of M-PCNL and S-PCNL for managing renal calculi. Methods This randomized study enrolled 60 patients with renal stones, comparing the efficacy and safety of M-PCNL (Group A) and S-PCNL (Group B) procedures. Preoperative assessments, surgical procedures, and postoperative care were conducted, and outcomes such as operating time, stone clearance, analgesic requirement, and hospital stay were evaluated. Data analysis was performed using SPSS software, with comparisons between groups conducted using the Chi-square test and Student t test. Results M-PCNL had a longer operation time (133.73 ± 29.18 min) than S-PCNL (48.6 ± 17.88 min, p  = 0.009) but a lower mean drop in hemoglobin levels (0.14 ± 0.01 g/dL vs. 0.82 ± 0.05 g/dL, p  = 0.032). The success rates (stone-free rate) were significantly different, with 100% in the M-PCNL group and 86.7% in the S-PCNL group ( p  = 0.040). Complications were generally fewer in the M-PCNL group, including postoperative fever in 2 cases (M-PCNL) vs. 8 cases (S-PCNL) and mild collection in 4 cases (M-PCNL) vs. 26 cases (S-PCNL). Conclusions M-PCNL is an effective and safer method for managing renal calculi smaller than 3 cm, offering a higher stone-free rate, lower postoperative pain, and shorter hospital stays compared to S-PCNL. Despite longer operation times due to stone fragmentation, M-PCNL has fewer complications, including lower bleeding rates, hemoglobin drop, and leakage, and can be performed using an ureteroscope when a miniperc scope is unavailable.

Background There are many percutaneous coronary approaches. The most commonly used one is the radial artery because of its lowest risk of adverse vascular events. However, it could not be an option in some situations as congenital radial artery hypoplasia and spasm. In these cases, the second most common access is the femoral artery. The current literature over the brachial artery access is controversial. Thus, the aim of this study was to verify the brachial artery approach's effectiveness and safety. Results We studied 300 patients who underwent elective coronary angiography and angioplasty in our institution with failed radial access between August 2022 and February 2023. They were classified into two groups; 150 patients with brachial access and 150 with femoral access. Access, procedural and fluoroscopy times were recorded. All patients were examined carefully immediately after the procedure and before discharge to assess any complications. Left brachial access was used more frequently than left femoral access (32.7% vs. 22.7%, P  = 0.05), but no significant difference noted regarding right sided or bilateral access. Procedure time, fluoroscopy time, and contrast volume did not significantly differ ( P  = 0.19, 0.06 and 0.1 respectively). However, brachial group had shorter access time (2.6 ± 1.1 vs. 3.4 ± 0.7 min, P  = 0.05) and hospital stay (3.5 ± 1.1 vs. 5.9 ± 1.3 days, P  <  0.001). Regarding major and minor complications (especially hematomas), they were significantly less in the brachial arm ( P  = 0.04 and P  = 0.05, respectively). Conclusions Brachial access is a safe, efficient and non-inferior to the femoral route for coronary intervention whenever radial access is not an option.

In this study, the LC-HRMS-assisted chemical profiling of Hyrtios erectus sponge led to the annotation of eleven major compounds (1–11). H. erectus-derived crude extract (HE) was tested in vitro for its antiproliferative activity against three human cancer cell lines, Hep-G2 (human liver cancer cell line), MCF-7 (breast cancer cell line), and Caco-2 (colon cancer cell line), before and after encapsulation within niosomes. Hyrtios erectus extract showed moderate in vitro antiproliferative activities towards the studied cell lines with IC50 values 18.5 ± 0.08, 15.2 ± 0.11, and 13.4 ± 0.12, respectively. The formulated extract-containing niosomes (size 142.3 ± 10.3 nm, PDI 0.279, and zeta potential 22.8 ± 1.6) increased the in vitro antiproliferative activity of the entrapped extract significantly (IC50 8.5 ± 0.04, 4.1 ± 0.07, and 3.4 ± 0.05, respectively). A subsequent computational chemical study was performed to build a sponge–metabolite–targets–cancer diseases network, by focusing on targets that possess anticancer activity toward the three cancer types: breast, colon, and liver. Pubchem, BindingDB, and DisGenet databases were used to build the network. Shinygo and KEGG databases in addition to FunRich software were used for gene ontology and functional analysis. The computational analysis linked the metabolites to 200 genes among which 147 genes related to cancer and only 64 genes are intersected in the three cancer types. The study proved that the co-occurrence of compounds 1, 2, 3, 7, 8, and 10 are the most probable compounds possessing cytotoxic activity due to large number of connections to the intersected cytotoxic genes with edges range from 9-14. The targets possess the anticancer effect through Pathways in cancer, Endocrine resistance and Proteoglycans in cancer as mentioned by KEGG and ShinyGo 7.1 databases. This study introduces niosomes as a promising strategy to promote the cytotoxic potential of H. erectus extract.

Sponge- sp. (Family: Spongiidae) is a coastal sponge that possesses a broad variety of natural-products. However, the exact chemical constituents and cytotoxic activity of the extract are still undefinable. In the present study, the metabolomic profiling of sp. dereplicated 20 compounds, utilizing liquid chromatography coupled with high-resolution mass spectrometry (LC-HRESIMS). derived crude extract, before and after encapsulation within nanosized liposomes, was in vitro screened against hepatic, breast, and colorectal carcinoma human cell lines (HepG2, MCF-7, and Caco-2, respectively). The identified metabolites were fit to diverse chemical classes, covering diterpenes, an indole alkaloid, sesterterpenoid, sterol, and methylherbipoline salt. Comprehensive in silico experiments predicted several compounds in the sponge-derived extract (eg, compounds - ) to have an anticancer potential via targeting multiple targets. The crude extract showed moderate antiproliferative activities towards studied cell lines with IC values range from 10.7 to 12.4 µg/mL. The formulated extract-containing liposomes (size 141±12.3nm, PDI 0.222, zeta potential 20.8 ± 2.3), significantly enhanced the in vitro anticancer activity of the entrapped extract (IC values ranged from 1.7 to 4.1 µg/mL). Encapsulation of both the hydrophilic and the lipophilic components of the extract within the lipid-based nanovesicles enhanced the cellular uptake and accessibility of the entrapped cargo. This study introduces liposomal nano-vesicles as a promising approach to improve the therapeutic potential of sponge-derived extracts.

Propolis is a honeybee product that contains a mixture of natural substances with a broad spectrum of biological activities. However, the clinical application of propolis is limited due to the presence of a myriad of constituents with different physicochemical properties, low bioavailability and lack of appropriate formulations. In this study, a modified injection technique (spraying technique) has been developed for the encapsulation of the Egyptian propolis within liposomal formulation. The effects of three variables (lipid molar concentration, drug loading and cholesterol percentage) on the particle size and poly dispersity index (PDI) were studied using response surface methodology and the Box–Behnken design. Response surface diagrams were used to develop an optimized liposomal formulation of the Egyptian propolis. A comparative study between the optimized liposomal formulation prepared either by the typical ethanol injection method (TEIM) or the spraying method in terms of particle size, PDI and the in-vitro anti-proliferative effect against human melanoma cell line A375 was carried out. The spraying method resulted in the formation of smaller propolis-loaded liposomes compared to TEIM (particle sizes of 90 ± 6.2 nm, and 170 ± 14.7 nm, respectively). Furthermore, the IC50 values against A375 cells were found to be 3.04 ± 0.14, 4.5 ± 0.09, and 18.06 ± 0.75 for spray-prepared propolis liposomes (PP-Lip), TEIM PP-Lip, and propolis extract (PE), respectively. The encapsulation of PE into liposomes is expected to improve its cellular uptake by endocytosis. Moreover, smaller and more uniform liposomes obtained by spraying can be expected to achieve higher cellular uptake, as the ratio of liposomes or liposomal aggregates that fall above the capacity of cell membrane to “wrap” them will be minimized.

Cancer is a major disease that threatens human health all over the world. Intervention and prevention in premalignant processes are successful ways to prevent cancer from striking. On the other hand, the marine ecosystem is a treasure storehouse of promising bioactive metabolites. The use of such marine products can be optimized by selecting a suitable nanocarrier. Therefore, epi-obtusane, previously isolated from Aplysia oculifera, was investigated for its potential anticancer effects toward cervical cancer through a series of in vitro assays in HeLa cells using the MTT assay method. Additionally, the sesquiterpene was encapsulated within a liposomal formulation (size = 130.8 ± 50.3, PDI = 0.462, zeta potential −12.3 ± 2.3), and the antiproliferative potential of epi-obtusane was investigated against the human cervical cancer cell line HeLa before and after encapsulation with liposomes. Epi-obtusane exhibited a potent effect against the HeLa cell line, while the formulated molecule with liposomes increased the in vitro antiproliferative activity. Additionally, cell cycle arrest analysis, as well as the apoptosis assay, performed via FITC-Annexin-V/propidium iodide double staining (flow cytofluorimetry), were carried out. The pharmacological network enabled us to deliver further insights into the mechanism of epi-obtusane, suggesting that STAT3 might be targeted by the compound. Moreover, molecular docking showed a comparable binding score of the isolated compound towards the STAT3 SH2 domain. The targets possess an anticancer effect through the endometrial cancer pathway, regulation of DNA templated transcription, and nitric oxide synthase, as mentioned by the KEGG and ShinyGo 7.1 databases.

The olive tree is a venerable Mediterranean plant and often used in traditional medicine. The main aim of the present study was to evaluate the effect of Olea europaea L. cv. Arbosana leaf extract (OLE) and its encapsulation within a spanlastic dosage form on the improvement of its pro-oxidant and antiproliferative activity against HepG-2, MCF-7, and Caco-2 human cancer cell lines. The LC-HRESIMS-assisted metabolomic profile of OLE putatively annotated 20 major metabolites and showed considerable in vitro antiproliferative activity against HepG-2, MCF-7, and Caco-2 cell lines with IC50 values of 9.2 ± 0.8, 7.1 ± 0.9, and 6.5 ± 0.7 µg/mL, respectively. The encapsulation of OLE within a (spanlastic) nanocarrier system, using a spraying method and Span 40 and Tween 80 (4:1 molar ratio), was successfully carried out (size 41 ± 2.4 nm, zeta potential 13.6 ± 2.5, and EE 61.43 ± 2.03%). OLE showed enhanced thermal stability, and an improved in vitro antiproliferative effect against HepG-2, MCF-7, and Caco-2 (IC50 3.6 ± 0.2, 2.3 ± 0.1, and 1.8 ± 0.1 µg/mL, respectively) in comparison to the unprocessed extract. Both preparations were found to exhibit pro-oxidant potential inside the cancer cells, through the potential inhibitory activity of OLE against glutathione reductase and superoxide dismutase (IC50 1.18 ± 0.12 and 2.33 ± 0.19 µg/mL, respectively). These inhibitory activities were proposed via a comprehensive in silico study to be linked to the presence of certain compounds in OLE. Consequently, we assume that formulating such a herbal extract within a suitable nanocarrier would be a promising improvement of its therapeutic potential.

Background. Atrial septal defect (ASD) is one of the commonest forms of congenital heart disease in adults. It may result in increased cardiac dimensions due to volume overload and prolongation of atrial electromechanical delay (AEMD). We aimed to investigate the effects of percutaneous ASD closure on both cardiac mechanical and electric remodelling after 6 months of ASD closure. Subjects and Methods. A total of 126 adult patients with secundum type ASD admitted to our institution for transcatheter device closure were retrospectively enrolled in this study. History taking, physical examination, electrocardiographic assessment, and echocardiographic examination at baseline and 6 months after ASD closure were done in all patients. Results. After percutaneous ASD closure, there was a significant increase in left ventricular (LV) dimensions and transmitral E/A ratio (P < 0.001) without a significant effect on systolic function (P = 0.83), and a significant reduction of right ventricular (RV) dimensions and pulmonary artery systolic pressure (PASP) (P < 0.001), compared to pre-procedural values. Furthermore, regarding RV functions, there was a significant improvement involving echocardio-graphic parameters of RV myocardial performance index (RVMPI), RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), pulsed tissue Doppler S' wave velocity and RV global longitudinal strain (RVGLS) of the free wall (P < 0.001). Regarding electric remodelling, atrial electromechanical conduction times and AEMD were significantly shortened after closure (P < 0.001). Conclusions. Percutaneous ASD closure has a favorable and positive impact on RV volumes and functions and on the AEMD properties. ASD closure does not have a negative effect on the LV systolic function.

Extensive analytical and functional characterization of a biotherapeutic product is a regulatory requirement, more so for biosimilar products where approval is contingent on the manufacturer’s ability to demonstrate comparability of their product to the corresponding reference product. Typical biotherapeutic formulations contain multiple excipients that are meant to stabilize the product and these can impact certain analytical and functional techniques that are typically used in the above-mentioned characterization and comparability exercises. In this study, we elucidate this interference using Trastuzumab (Tmab) reference product, Herclon, and its commercially available biosimilars, Herzuma and Vivitra, as an example. Excipients were removed one at a time from the drug product and impact of this removal on a spectrum of analytical and functional tools was examined. Removal of certain excipients (Trehalose, L-histidine HCl and Polysorbate 20) was found to impact the results of charge variant analysis (cation exchange HPLC), secondary structure analysis (FTIR and far-UV CD spectroscopy), and tertiary structure analysis (near-UV CD and intrinsic FLR spectroscopy) For charge variants, differences up to 3.62% in basic species were observed, while FTIR spectra in the amide I region were significantly impacted. The intrinsic fluorescence spectra displayed major wavelength maxima shifts of up to 6 nm. In view of these results, it is recommended that biosimilar manufacturers consider the impact of differences in formulation in the samples that are being compared as well as the impact of excipient removal, if they are extracting the therapeutic moiety from the drug product for comparability analysis (routinely done by biosimilar manufacturers).