Privacy-preserving blockchain-based federated learning for brain tumor segmentation.

Improved data sharing between healthcare providers can lead to a higher probability of accurate diagnosis, more effective treatments, and enhanced capabilities of healthcare organizations. One critical area of focus is brain tumor segmentation, a complex task due to the heterogeneous appearance, irregular shape, and variable location of tumors. Accurate segmentation is essential for proper diagnosis and effective treatment planning, yet current techniques often fall short due to these complexities. However, the sensitive nature of health data often prohibits its sharing. Moreover, the healthcare industry faces significant issues, including preserving the privacy of the model and instilling trust in the model. This paper proposes a framework to address these privacy and trust issues by introducing a mechanism for training the global model using federated learning and sharing the encrypted learned parameters via a permissioned blockchain. The blockchain-federated learning algorithm we designed aggregates gradients in the permissioned blockchain to decentralize the global model, while the introduced masking approach retains the privacy of the model parameters. Unlike traditional raw data sharing, this approach enables hospitals or medical research centers to contribute to a globally learned model, thereby enhancing the performance of the central model for all participating medical entities. As a result, the global model can learn about several specific diseases and benefit each contributor with new disease diagnosis tasks, leading to improved treatment options. The proposed algorithm ensures the quality of model data when aggregating the local model, using an asynchronous federated learning procedure to evaluate the shared model's quality. The experimental results demonstrate the efficacy of the proposed scheme for the critical and challenging task of brain tumor segmentation. Specifically, our method achieved a 1.99% improvement in Dice similarity coefficient for enhancing tumors and a 19.08% reduction in Hausdorff distance for whole tumors compared to the baseline methods, highlighting the significant advancement in segmentation performance and reliability.

Haplophyllum tuberculatum (Forssk.) A. Juss Essential Oils: Seasonal Contents Variation, Bioactivity of the Traditionally-favored, High-yield and Frequent-use Summer Season Oil.

Haplophyllum tuberculatum (Forssk.) A.Juss. volatile oils were obtained by distillation of the aerial parts of the plant growing in Libya during the summer and spring seasons. A yield and componential analysis revealed that the summer season oil, which is frequently used in traditional medicaments by North African communities, was high in yield (0.858%) compared to the spring season oil (0.47%), and distinguished by the presence of major and various diverse constituents, some of which are considered chemical markers. Owing to the traditional and high incidence of use of the summer-produced essential oil for the treatment of several disorders, including hepatic diseases, and fatigue, the oil was pharmacologically investigated for its varied bioactivities of anti-microbial, in vivo anti-oxidant, and in vitro anti-cancer properties. Thirty-three compounds were identified and represented 96.2% of the peaks in the GCchromatogram of the summer oil, in which the major volatile constituents were δ-3-carene (21.5%), bornyl acetate (16.9%), and limonene aldehyde (15.2%). The summer-based essential oil of the plant demonstrated moderate anti-bacterial activity against Gram-positive bacteria and a relatively strong antibacterial effect against Gram-negative bacteria as compared to the positive antibacterial controls, ampicillin and gentamicin, respectively. Also, antifungal activity against Aspergillus sp. was observed. The summerproduced oil also exhibited in vivo antioxidant and in vitro anti-cancer activities.

Graphene oxide-induced, reactive oxygen species-mediated mitochondrial dysfunctions and apoptosis: high-dose toxicity in normal cells.

Aim: The cytotoxic effects of graphene oxide nanoparticles (GONPs) using MTT assays, observance of apoptotic markers, and oxidative stress were outlined. Materials & methods: Rat embryonic fibroblasts (REFs) and human epithelial breast cells (HBLs) were used at 250, 500 and 750 µg/ml concentrations. Results: Significant cytotoxic and apoptotic effects were observed. Analyses of CYP2E1 and malondialdehyde concentrations in REF and HBL-100 cell lines after exposing to GONPs confirmed the nanomaterials toxicity. However, the glutathione levels in REF and HBL-100 cell lines showed a substantial reduction compared with the control. The cytochrome CYP2E1, glutathione, malondialdehyde and caspase-3 alterations provided a plausible interlinked relationship. Conclusion: The study confirmed the GONPs cytotoxic effects on REF and HBL-100 cell lines. The outcome suggested caution in wide-spread applications of GONPs, which could have implications for occupational health also.

Bacterial extracellular vesicles induced oxidative stress and mitophagy through mTOR pathways in colon cancer cells, HT-29: Implications for bioactivity.

Bacterial-extracellular-vesicles (BEVs) derived from Escherichia coli, strain-A5922, were used as a therapeutic tool to treat colon cancer cells, HT-29. BEVs induced oxidative stress, and observed mitochondrial autophagy, known as mitophagy, were crucial in initiation of treatment. The mitophagy, induced by the BEVs in HT-29 cells, produced adenocarcinomic cytotoxicity, and stopped the cells growth. The trigger for mitophagy, and an increase in productions of reactive oxygen species led to cellular oxidative stress, that eventually led to cells death. A reduction in the mitochondrial membrane potential, and an increase in the PINK1 expressions confirmed the oxidative stress involvements. The BEVs triggered cytotoxicity, and mitophagy in the HT-29 carcinoid cells, channelized through the Akt/mTOR pathways connecting the cellular oxidative stress, effectively played its part to cause cells death. These findings substantiated the BEVs' potential as a plausible tool for treating, and possibly preventing the colorectal cancer.

In Vitro and In Vivo Functional Viability, and Biocompatibility Evaluation of Bovine Serum Albumin-Ingrained Microemulsion: A Model Based on Sesame Oil as the Payload for Developing an Efficient Drug Delivery Platform.

Combination of bovine serum albumin with microemulsions as constituting ingredient biopolymer has long been regarded an innovative method to address the surface functionalization and stability issues in the targeted payload deliveries, thereupon producing effectively modified microemulsions, which are superior in loading capacity, transitional and shelf-stability, as well as site-directed/site-preferred delivery, has become a favored option. The current study aimed to develop an efficient, suitable and functional microemulsion system encapsulating sesame oil (SO) as a model payload towards developing an efficient delivery platform. UV-VIS, FT-IR, and FE-SEM were used to characterize, and analyze the developed carrier. Physicochemical properties assessments of the microemulsion by dynamic light scattering size distributions, zeta-potential, and electron micrographic analyses were performed. The mechanical properties for rheological behavior were also studied. The HFF-2 cell line and hemolysis assays were conducted to ascertain the cell viability, and in vitro biocompatibility. The in vivo toxicity was determined based on a predicted median lethal dose (LD50) model, wherein the liver enzymes' functions were also tested to assess and confirm the predicted toxicity.

Phenanthroindolizidine Alkaloids Secondary Metabolites Diversity in Medicinally Viable Plants of the Genus Tylophora.

Plants of the genus Tylophora have commonly been used in traditional medicine in various communities, especially in the tropical and subtropical regions of climatic zones. Of the nearly 300 species reported in the Tylophora genus, eight are primarily used in various forms to treat a variety of bodily disorders based on the symptoms. Certain plants from the genus have found use as anti-inflammatory, anti-tumor, anti-allergic, anti-microbial, hypoglycemic, hypolipidemic, anti-oxidant, smooth muscle relaxant, immunomodulatory, and anti-plasmodium agents, as well as free-radical scavengers. Pharmacologically, a few plant species from the genus have exhibited broad-spectrum anti-microbial and anti-cancer activity, which has been proven through experimental evaluations. Some of the plants in the genus have also helped in alcohol-induced anxiety amelioration and myocardial damage repair. The plants belonging to the genus have also shown diuretic, anti-asthmatic, and hepato-protective activities. Tylophora plants have afforded diverse structural bases for secondary metabolites, mainly belonging to phenanthroindolizidine alkaloids, which have been found to treat several diseases with promising pharmacological activity levels. This review encompasses information on various Tylophora species, their distribution, corresponding plant synonyms, and chemical diversity of the secondary metabolic phytochemicals as reported in the literature, together with their prominent biological activities.

Salt-Tolerant Plants, Halophytes, as Renewable Natural Resources for Cancer Prevention and Treatment: Roles of Phenolics and Flavonoids in Immunomodulation and Suppression of Oxidative Stress towards Cancer Management.

Halophytes and xerophytes, plants with adequate tolerance to high salinity with strong ability to survive in drought ecosystem, have been recognized for their nutritional and medicinal values owing to their comparatively higher productions of secondary metabolites, primarily the phenolics, and the flavonoids, as compared to the normal vegetation in other climatic regions. Given the consistent increases in desertification around the world, which are associated with increasing salinity, high temperature, and water scarcity, the survival of halophytes due to their secondary metabolic contents has prioritized these plant species, which have now become increasingly important for environmental protection, land reclamation, and food and animal-feed security, with their primary utility in traditional societies as sources of drugs. On the medicinal herbs front, because the fight against cancer is still ongoing, there is an urgent need for development of more efficient, safe, and novel chemotherapeutic agents, than those currently available. The current review describes these plants and their secondary-metabolite-based chemical products as promising candidates for developing newer cancer therapeutics. It further discusses the prophylactic roles of these plants, and their constituents in prevention and management of cancers, through an exploration of their phytochemical and pharmacological properties, with a view on immunomodulation. The important roles of various phenolics and structurally diverse flavonoids as major constituents of the halophytes in suppressing oxidative stress, immunomodulation, and anti-cancer effects are the subject matter of this review and these aspects are outlined in details.

Antimicrobial, Antibiofilm, and Antioxidant Potentials of Four Halophytic Plants, Euphorbia chamaesyce, Bassia arabica, Fagonia mollis, and Haloxylon salicornicum, Growing in Qassim Region of Saudi Arabia: Phytochemical Profile and In Vitro and In Silico Bioactivity Investigations.

The current study aimed to investigate the phytochemical contents and antioxidant, antimicrobial, and antibiofilm activities of four halophytic plants, namely, Euphorbia chamaesyce, Bassia arabica, Fagonia mollis, and Haloxylon salicornicum, native to central Saudi Arabia. The alcoholic extract of E. chamaesyce was found to be the most potent in various bioactivities-based evaluations and rich in polyphenols and flavonoid secondary metabolites, with 68.0 mg/g and 39.23 mg/g gallic acid and quercetin equivalents, respectively. Among all plants' extracts, the alcoholic extract of E. chamaesyce had the highest DPPH scavenging and metal chelating antioxidant activities at 74.15 Trolox equivalents and 16.28 EDTA equivalents, respectively. The highest antimicrobial activity of E. chamaesyce extract was found to be against Shigella flexneri, with a mean zone of inhibition diameter of 18.1 ± 0.2 mm, whereas the minimum inhibitory concentration, minimum biocidal concentration, minimum biofilm inhibitory concentration, and minimum biofilm eradication concentration values were 12.5, 25, 25, and 50 mg/mL, respectively. The LC-ESI-MS/MS analysis of the E. chamaesyce extract showed the presence of six flavonoids and ten phenolic constituents. The in silico binding of the E. chamaesyce extract's constituents to Staphylococcus aureus tyrosyl-tRNA synthetase enzyme displayed -6.2 to -10.1 kcal/mol binding energy values, suggesting that these constituents can contribute to the antimicrobial properties of the plant extract, making it an essential medicinal ingredient. In conclusion, these results warrant further investigation to standardize the antimicrobial profiles of these plant extracts.

Prevalence of extra-articular tibia valga morphology in valgus knees and its implications for primary total knee arthroplasty.

INTRODUCTION: Tibia valga, an extra-articular valgus deformity of the tibia, is common in valgus knees and can result in component misplacement and early total knee arthroplasty (TKA) failure. However, the prevalence and importance of tibia valga in TKA have been seldom reported. This study aims to describe the prevalence and characteristics of tibia valga morphology in valgus knees and describe implications for surgical planning in primary TKA. METHODS: We prospectively examined pre-operative weightbearing whole-body EOS digital radiographs of patients with knee osteoarthritis listed for TKA between December 2018 and December 2020. Hip-knee-ankle angle (HKA), mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), joint line convergence angle (JLCA) and tibial morphology with centre of rotation of angulation of tibia (CORA-tibia) were measured and analysed. RESULTS: In 830 knees, 253 (30%) and 577 (70%) were classified as valgus and varus, respectively. In valgus knees, 89 knees (35%) had tibia valga. Median CORA-tibia was 2.8° (range 0.2°-10.9°). Tibia valga knees had no difference in mLDFA, higher HKA (5.0o versus 3.0°, p = 0.002) and mMPTA (89.6° versus 88.1°, p < 0.01), and lower JLCA (2.1° versus 2.3°, p < 0.01) compared to non-tibia valga knees. Tibia valga deformity was weakly positively correlated with valgus HKA (ρ = 0.23, p < 0.001) and mMPTA (ρ = 0.38, p < 0.001). In varus knees, there were 52 cases of tibia valga (9%) with median CORA-tibia of 3.0° (range 0.5°-5.5°). Tibia valga knees had higher mMPTA (87.0° versus 85.2°, p < 0.05) and no difference in HKA, mLDFA and JLCA. CORA-tibia was weakly positively correlated with mMPTA. CONCLUSIONS: Valgus knees may have an extra-articular deformity of the tibia which might be the primary contributor of the overall valgus HKA deformity rather than the distal femoral anatomy. To detect the deformity, full leg-length radiographs should be acquired pre-operatively. Intramedullary instrumentation should be used cautiously in knees with tibia valga when performing TKA.

Comparative Anticancer Potentials of Taxifolin and Quercetin Methylated Derivatives against HCT-116 Cell Lines: Effects of O-Methylation on Taxifolin and Quercetin as Preliminary Natural Leads.

Six flavonoids present in Pulicaria jaubertii, i.e., 7,3'-di-O-methyltaxifolin (1), 3'-O-methyltaxifolin (2), 7-O-methyltaxifolin (3), taxifolin (4), 3-O-methylquercetin (5), and quercetin (6), were tested for their anticancer activities. The methylated flavonoids, compounds 1-3 and 5, were evaluated for their anticancer activities in comparison to the non-methylated parent flavonoids taxifolin (4) and quercetin (6). The structures of the known compounds were reconfirmed by spectral analyses using 1H and 13C NMR data comparisons and HRMS spectrometry. The anticancer activity of these compounds was evaluated in colon cancer, HCT-116, and noncancerous, HEK-293, cell lines using the MTT antiproliferative assays. The caspase-3 and caspase-9 expressions and DAPI (4', 6-diamidino-2-phenylindole) staining assays were used to evaluate the apoptotic activity. All the compounds exhibited antiproliferative activity against the HCT-116 cell line with IC50 values at 33 ± 1.25, 36 ± 2.25, 34 ± 2.15, 32 ± 2.35, 34 ± 2.65, and 36 ± 1.95 µg/mL for compounds 1 to 6, respectively. All the compounds produced a significant reduction in HCT-116 cell line proliferation, except compounds 2 and 6. The viability of the HEK-293 normal cells was found to be significantly higher than the viability of the cancerous cells at all of the tested concentrations, thus suggesting that all the compounds have better inhibitory activity on the cancer cell line. Apoptotic features such as chromatin condensation and nuclear shrinkage were also induced by the compounds. The expression of caspase-3 and caspase-9 genes increased in HCT-116 cell lines after 48 h of treatment, suggesting cell death by the apoptotic pathways. The molecular docking studies showed favorable binding affinity against different pro- and antiapoptotic proteins by these compounds. The docking scores were minimum as compared to the caspase-9, caspase-3, Bcl-xl, and JAK2.

SPIONs Conjugate Supported Anticancer Drug Doxorubicin's Delivery: Current Status, Challenges, and Prospects.

Considerable efforts have been directed towards development of nano-structured carriers to overcome the limitations of anticancer drug, doxorubicin's, delivery to various cancer sites. The drug's severe toxicity to cardio and hepatic systems, low therapeutic outcomes, inappropriate dose-demands, metastatic and general resistance, together with non-selectivity of the drug have led to the development of superparamagnetic iron oxide nanoparticles (SPIONs)-based drug delivery modules. Nano-scale polymeric co-encapsulation of the drug, doxorubicin, with SPIONs, the SPIONs surface end-groups' cappings with small molecular entities, as well as structural modifications of the SPIONs' surface-located functional end-groups, to attach the doxorubicin, have been achieved through chemical bonding by conjugation and cross-linking of natural and synthetic polymers, attachments of SPIONs made directly to the non-polymeric entities, and attachments made through mediation of molecular-spacer as well as non-spacer mediated attachments of several types of chemical entities, together with the physico-chemical bondings of the moieties, e.g., peptides, proteins, antibodies, antigens, aptamers, glycoproteins, and enzymes, etc. to the SPIONs which are capable of targeting multiple kinds of cancerous sites, have provided stable and functional SPIONs-based nano-carriers suitable for the systemic, and in vitro deliveries, together with being suitable for other biomedical/biotechnical applications. Together with the SPIONs inherent properties, and ability to respond to magnetic resonance, fluorescence-directed, dual-module, and molecular-level tumor imaging; as well as multi-modular cancer cell targeting; magnetic-field-inducible drug-elution capacity, and the SPIONs' magnetometry-led feasibility to reach cancer action sites have made sensing, imaging, and drug and other payloads deliveries to cancerous sites for cancer treatment a viable option. Innovations in the preparation of SPIONs-based delivery modules, as biocompatible carriers; development of delivery route modalities; approaches to enhancing their drug delivery-cum-bioavailability have explicitly established the SPIONs' versatility for oncological theranostics and imaging. The current review outlines the development of various SPIONs-based nano-carriers for targeted doxorubicin delivery to different cancer sites through multiple methods, modalities, and materials, wherein high-potential nano-structured platforms have been conceptualized, developed, and tested for, both, in vivo and in vitro conditions. The current state of the knowledge in this arena have provided definite dose-control, site-specificity, stability, transport feasibility, and effective onsite drug de-loading, however, with certain limitations, and these shortcomings have opened the field for further advancements by identifying the bottlenecks, suggestive and plausible remediation, as well as more clear directions for future development.

Oncolytic Newcastle Disease Virus Co-Delivered with Modified PLGA Nanoparticles Encapsulating Temozolomide against Glioblastoma Cells: Developing an Effective Treatment Strategy.

Glioblastoma multiforme (GBM) is considered to be one of the most serious version of primary malignant tumors. Temozolomide (TMZ), an anti-cancer drug, is the most common chemotherapeutic agent used for patients suffering from GBM. However, due to its inherent instability, short biological half-life, and dose-limiting characteristics, alternatives to TMZ have been sought. In this study, the TMZ-loaded PLGA nanoparticles were prepared by employing the emulsion solvent evaporation technique. The prepared TMZ-PLGA-NPs were characterized using FT-IR, zeta potential analyses, XRD pattern, particle size estimation, TEM, and FE-SEM observations. The virotherapy, being safe, selective, and effective in combating cancer, was employed, and TMZ-PLGA-NPs and oncolytic Newcastle Disease Virus (NDV) were co-administered for the purpose. An AMHA1-attenuated strain of NDV was propagated in chicken embryos, and the virus was titrated in Vero-slammed cells to determine the infective dose. The in vitro cytotoxic effects of the TMZ, NDV, and the TMZ-PLGA-NPs against the human glioblastoma cancer cell line, AMGM5, and the normal cell line of rat embryo fibroblasts (REFs) were evaluated. The synergistic effects of the nano-formulation and viral strain combined therapy was observed on the cell lines in MTT viability assays, together with the Chou-Talalay tests. The outcomes of the in vitro investigation revealed that the drug combinations of NDV and TMZ, as well as NDV and TMZ-PLGA-NPs exerted the synergistic enhancements of the antitumor activity on the AMGM5 cell lines. The effectiveness of both the mono, and combined treatments on the capability of AMGM5 cells to form colonies were also examined with crystal violet dyeing tests. The morphological features, and apoptotic reactions of the treated cells were investigated by utilizing the phase-contrast inverted microscopic examinations, and acridine orange/propidium iodide double-staining tests. Based on the current findings, the potential for the use of TMZ and NDV as part of a combination treatment of GBM is significant, and may work for patients suffering from GBM.

Galangin/ß-Cyclodextrin Inclusion Complex as a Drug-Delivery System for Improved Solubility and Biocompatibility in Breast Cancer Treatment.

The purpose of this study was to evaluate the potential of a newly modified cyclodextrin derivative, water-soluble ß-cyclodextrin-epichlorohydrin (ß-CD), as an effective drug carrier to enhance the poor solubility and bioavailability of galangin (GAL), a poorly water-soluble model drug. In this regard, inclusion complexes of GAL/ß-CDP were prepared. UV-VIS spectrophotometry, Fourier-transform infrared spectroscopy (FTIR), X-ray crystallography (XRD), zeta potential analysis, particle size analysis, field emission scanning electron microscopy (FESEM), and transmission electron microscopy (TEM) were applied to characterize the synthesized GAL/ß-CD. Michigan Cancer Foundation-7 (MCF-7; human breast cancer cells) and rat embryo fibroblast (REF; normal cells) were employed to examine the in vitro cytotoxic effects of GAL/ß-CD using various parameters. The dye-based tests of MTT and crystal violet clearly exhibited that GAL/ß-CD-treated cells had a reduced proliferation rate, an influence that was not found in the normal cell line. The cells' death was found to follow apoptotic mechanisms, as revealed by the dye-based test of acridine orange/ethidium bromide (AO/EtBr), with the involvement of the mitochondria via caspase-3-mediated events, as manifested by the Rh 123 test. We also included a mouse model to examine possible in vivo toxic effects of GAL/ß-CD. It appears that the inclusion complex does not have a significant influence on normal cells, as indicated by serum levels of kidney and liver enzymatic markers, as well as thymic and splenic mass indices. A similar conclusion was reached on the histological level, as manifested by the absence of pathological alterations in the liver, kidney, thymus, spleen, heart, and lung.

Synthesis and Anti-Cancer Activity of New Pyrazolinyl-Indole Derivatives: Pharmacophoric Interactions and Docking Studies for Identifying New EGFR Inhibitors.

Newly designed series of indole-containing pyrazole analogs, pyrazolinylindoles, were synthesized, and their structures were confirmed based on the spectral data of the 1H NMR, 13C NMR, and HR-MS analyses. Preliminary anti-cancer activity testings were carried out by the National Cancer Institute, United States of America (NCI, USA). Compounds HD02, HD05, and HD12 demonstrated remarkable cytotoxic activities against nine categories of cancer types based cell line panels which included leukemia, colon, breast, melanoma, lungs, renal, prostate, CNS, and ovarian cancer cell lines. The highest cytotoxic effects were exhibited by the compounds HD02 [1-(5-(1-H-indol-3-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-phenylethanone], HD05 [1-(3-(4-chlorophenyl)-5-(1H-indol-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)-2-phenoxyethanone], and HD12 [(3-(4-chlorophenyl)-5-(1H-indol-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)(pyridin-4-yl)methanone] against some of the 56 types of NCI-based cell lines in different panels. Compound HD05 showed the maximum range of cancer cell growth inhibitions against all categories of the cell lines in all nine panels. On average, in comparison to the referral standard, imatinib, at a dose level of 10 µM, the HD05 showed significant activity against leukemia in the range of 78.76%, as compared to the imatinib at 9% of cancer cells' growth inhibitions. Molecular docking simulation studies were performed in silico on the epidermal growth factor receptor (EGFR) tyrosine kinase, in order to validate the activity.

In Vitro Anti-Proliferative, and Kinase Inhibitory Activity of Phenanthroindolizidine Alkaloids Isolated from Tylophora indica.

The phenanthroindolizidine alkaloid (-)-tylophorine has been reported for its significant anticancer activity working through different biomechanistic pathways. The current study aimed to evaluate the anticancer activity of phenanthroindolizidine alkaloids isolated from Tylophora indica. Six phenanthroindolizidine alkaloid (compounds 1-6) in addition to septicine (7), chlorogenic acid (8), and chlorogenic acid methyl ester (9) were isolated from Tylophora indica using different chromatographic techniques including vacuum liquid chromatography (VLC) and preparative high performance liquid chromatography (HPLC). The isolated compounds structures' were determined using various spectro-analytical techniques, i.e., 1H-NMR, 13C-NMR, and mass spectrometry. The isolates' structural stereochemistry and structural geometries were determined with the help of chiroptical techniques together with comparisons with the available standard samples. The in vitro anti-proliferative activity on three different cell lines, MCF-7, HepG2, and HCT-116 were evaluated. Among all the isolated compounds, tylophorinidine (5) was the most active cytotoxic agent with the lowest IC50 values at 6.45, 4.77, and 20.08 µM against MCF-7, HepG2, and HCT-116 cell lines, respectively. The bioactivities were also validated by the in vitro kinase receptors inhibition assay. Compound (5) also exhibited the highest activity with lowest IC50 values (0.6 and 1.3 µM against the Aurora-A and Aurora-B enzymes, respectively), as compared with all the isolated alkaloidal products. The structure activity relationship on the molecular properties, molecular attributes, and bioactivity levels were analyzed, interrelated, and the molecular docking studies on two different receptors, Aurora-A and Aurora-B, were determined, which provided the confirmations of the bioactivity with receptor-ligand geometric disposition, energy requirements, lipophilicity, and detailed the binding pharmacophore involvements responsible for bioactivity elicitations.

Copper Oxide Nanoparticle-Decorated Carbon Nanoparticle Composite Colloidal Preparation through Laser Ablation for Antimicrobial and Antiproliferative Actions against Breast Cancer Cell Line, MCF-7.

Copper oxide (CuO) nanoparticle- (NP-) decorated carbon NPs (CNPs) were produced as colloidal suspension through pulsed laser ablation technique in liquid (PLAL) medium. The antimicrobial activity of the produced NPs was tested against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), and anticancer activity was tested against breast cancer cell line, MCF-7, together with the biocompatibility assessment of these NPs. The X-ray diffraction (XRD) patterns of the obtained CNPs showed peaks at 26.58° and 43.78° (2θ) identical to (002) and (111) planes, respectively, of the carbon phases. It also displayed new peaks at 38.5° and 48.64° (2θ) after doping with CuO NPs. Transmission electron microscope (TEM) images revealed the crystalline nature with the spherical shape of the prepared CNPs with 5-40 nm diameter ranges. In addition, the NP effects on the bacterial cell walls and nucleic acid were confirmed using a scanning electron microscope (SEM) and microscopic fluorescence analysis. The NPs showed antibacterial activity through SEM examinations against the pathogenic microbial species, S. aureus and E. coli. In the cellular material release assay, the optical density of the bacterial cells, treated with NPs, displayed a significant increase with the time of exposure to NPs, and the cytotoxicity reached more than 80% of the level for the CNPs decorated with CuO NPs. The morphology of the MCF-7 cells treated with NPs decreased numbers, and the loss of contact with the surrounding cells was observed. These results confirmed that the CNPs decorated with CuO NPs have no observable side effects and can be safely used for therapeutic applications. It is also noteworthy that it is the first report of preparation of CuO NPs decorated with CNPs (CuO NPs-CNPs) by PLAL, and the produced NPs showed antimicrobial antiproliferative activities against breast cancer cell lines, MCF-7. The main advantage of the PLAL technique of synthesizing CuO NPs-CNPs provided a two-step, cost-effective, and eco-friendly method.

Anthocyanins: Traditional Uses, Structural and Functional Variations, Approaches to Increase Yields and Products' Quality, Hepatoprotection, Liver Longevity, and Commercial Products.

Anthocyanins are water-soluble, colored compounds of the flavonoid class, abundantly found in the fruits, leaves, roots, and other parts of the plants. The fruit berries are prime sources and exhibit different colors. The anthocyanins utility as traditional medicament for liver protection and cure, and importance as strongest plants-based anti-oxidants have conferred these plants products different biological activities. These activities include anti-inflammation, liver protective, analgesic, and anti-cancers, which have provided the anthocyanins an immense commercial value, and has impelled their chemistry, biological activity, isolation, and quality investigations as prime focus. Methods in extraction and production of anthocyanin-based products have assumed vital economic importance. Different extraction techniques in aquatic solvents mixtures, eutectic solvents, and other chemically reactive extractions including low acid concentrations-based extractions have been developed. The prophylactic and curative therapy roles of the anthocyanins, together with no reported toxicity has offered much-needed impetus and economic benefits to these classes of compounds which are commercially available. Information retrieval from various search engines, including the PubMed®, ScienceDirect®, Scopus®, and Google Scholar®, were used in the review preparation. This imparted an outlook on the anthocyanins occurrence, roles in plants, isolation-extraction, structures, biosynthetic as well as semi- and total-synthetic pathways, product quality and yields enhancements, including uses as part of traditional medicines, and uses in liver disorders, prophylactic and therapeutic applications in liver protection and longevity, liver cancer and hepatocellular carcinoma. The review also highlights the integrated approach to yields maximizations to meet the regular demands of the anthocyanins products, also as part of the extract-rich preparations together with a listing of marketed products available for human consumption as nutraceuticals/food supplements.

Preparation of Iron Oxide and Titania-Based Composite, Core-Shell Populated, Nanoparticulates Material by Two-Step LASER Ablation in Aqueous Media as Antimicrobial and Anticancer Agents.

Iron oxide and titania-based composite nanoparticles (NPs) populated with core-shell structures, as part of the mixture of the monometallic NPs, were prepared in water medium by the two-fluence LASER ablation technique by applying 30 and 60 mJ/cm2 LASER energy irradiations. The prepared monometallics, composite, and core-shell NPs structures were confirmed from the XRD, TEM, and EDX analyses, followed by the FE-SEM and UV absorptions. Optically, the NPs exhibited an increase in the energy gap from 3.27 eV to 3.75 eV as LASER fluence increased from 30 mJ/cm2 to 60 mJ/cm2. The average NPs core size distributions for the core-shell material ranged at ∼70 nm with the shell thickness around 20 nm. The biggest NPs were of ∼170 nm size which were sparsely distributed. The magnetization behaviors of the NPs were also investigated using the vibrating sample magnetometer (VSM). The NPs showed antimicrobial activities against the pathogenic species: Escherichia coli and Staphylococcus aureus. The antimicrobial activities of the synthesized NPs, synthesized under the influence of magnetic fields, were found to be more potent than the NPs synthesized without the presence of any magnetic field. The NPs prepared under the influence of the magnetic fields also comparatively exhibited higher levels of cytotoxicity against lung cancer cell lines (A549) than the NPs prepared under no magnetic field's influence by the similar energy level effects of the LASER fluence. The flow cytometry analyses confirmed the NPs' cytotoxic impacts against the human lung cancer A549 cell lines through the initiation of apoptosis and promotion of the cell cycle arrest at the G1 phase of cell division. To further confirm the cytotoxic effects and the mechanism of the anticancer activity of the synthesized NPs against the A549 cell lines, several related parameters (cell viability, membrane permeability, nuclear intensity, and cytochrome-C release) were analyzed using the high-content screening (HCS) assay. The study suggested that the prepared NPs have potential as antimicrobial and also as anti-lung-cancer agents as tested in vitro. These NPs can also be part of combined chemotherapy in different oncological interventions, as well as a sonosensitizer in sonomagnetic heating-based therapy, especially for cancers.

Anterior approach to hip replacement and associated complications: an independent review.

BACKGROUND: Direct anterior approach (DAA) to hip replacement is increasingly popular. Despite the well-published benefits of early recovery, the approach can be associated with a number of complications that may be underreported. We aim to report the incidence of some of these complications in a large retrospective case series. METHODS: 270 consecutive DAA hip replacements are studied which are performed by a single high-volume hip surgeon from 2013 to 2015, not including the surgeon's learning curve. Operation and consultation records were screened, and focused questioning via telephone was employed to capture specific complications including dislocations, wound infections, lateral femoral cutaneous nerve (LFCN) injury and revision surgery. RESULTS: 240 of 270 patients or family were contactable. The mean age and body mass index of the cohort was 66 (range 30-89) years and 27 (range 18-40) kg/m2 respectively. The mean follow-up was 3.7 years. Wound issues were encountered in 24 patients (8.8%). There were 9 dislocations (3%). 27 (10%) patients needed revision surgery in the follow-up period. Reasons for revision included leg-length discrepancies, dislocations, ongoing pain and aseptic loosening. 9 (3.4%) patients had to return to operating theatre for reasons other than revision surgery. Symptoms of lateral femoral cutaneous nerve injury was reported by 54 patients (21%). CONCLUSIONS: While the short-term benefits of DAA have been widely reported, our review shows a relatively high rate of revision surgery. We feel that the enthusiasm for DAA should be tempered until further evidence is available.

Accuracy of one-dimensional templating on linear EOS radiography allows template-directed instrumentation in total knee arthroplasty.

BACKGROUND: Templating for total knee arthroplasty (TKA) is routinely performed on two-dimensional standard X-ray images and allows template-directed instrumentation. To date, there is no report on one-dimensional (1D) anteroposterior (AP) templating not requiring specific templating software. We aim to describe a novel technique and explore its reliability, accuracy and potential cost-savings. METHODS: We investigated a consecutive series of TKAs at one institution between January and July 2019. Patients with preoperative low-dose linear AP EOS radiography images were included. Implant component sizes were retrospectively templated on the AP view with the hospitals imaging viewing software by two observers who were blinded to the definitive implant size. Planning accuracy as well as inter- and intra-observer reliability was calculated. Cost-savings were estimated based on the reduction of trays indicated by the 1D templating size estimations. RESULTS: A total of 141 consecutive TKAs in 113 patients were included. Accuracy of 1D templating was as follows: exact match in 53% femoral and 63% tibial components, within one size in 96% femoral and 98% tibial components. Overall 58% of TKA components were planned correctly and 97% within one size. Inter- and intra-rater reliability was good (κ = 0.66) and very good (κ = 0.82), respectively. This templating process can reduce instrumentation from six to three trays per case and therefore halve sterilisation costs. CONCLUSIONS: The new 1D templating method using EOS AP imaging predicts component sizes in TKA within one size 97% of the time and can halve the number of instrumentation trays and sterilisation costs.