Search

A series of phthalazine derivatives have been synthesized using green protocol methods under microwave irradiation. This involved subjecting chlorophthalazine to microwave irradiation and employing various reagents, including hydrazine derivatives, primary and secondary amines, and active methylene, to generate the novel phthalazine derivatives. Subsequently, a comparison was made between the yield percentage and reaction time of the resulting products obtained from conventional methods and those obtained through microwave irradiation. The structures of all new compounds were confirmed by physical properties and spectral analysis. The phthalazine compounds demonstrated significant anticancer activity against three cancer cell lines and showed promising selectivity when compared with doxorubicin. Compound 6 exhibited the best anticancer activity, with IC50 1.739 µM, 0.384 µM, and 1.52 µM against MCF7, HCT116, and HepG2 cell lines, respectively. The docking results confirmed that the drugs exert their activity by inhibiting PARP-1. The binding scores were in accordance with the experimental IC50, with compound 6 exhibiting the best binding score and retaining the essential binding interactions with the active site. The results of our computational research have revealed that our phthalazine compounds possess a unique structure that effectively inhibits PARP-1.

Acanthospermum hispidum DC (Asteraceae), a traditional medicinal plant, plays a role as an alternative remedy for various diseases, such as bacterial and viral infections, jaundice, malaria, fever, gastrointestinal disorders, headache, convulsions, and snake bites. Flavonoids, alkaloids, saponins, tannins, terpenes, steroids, and cardioactive glycosides are the distinct classes of metabolites in the plant. Although A. hispidum was suggested as a promising antitumor phytomedicine, no studies identified its potential cytotoxic components. In this study, the cytotoxic compounds of A. hispidum were isolated using chromatographic techniques guided by in vitro MTT cytotoxicity assay against selected cancer cell lines; breast cancer (MCF7), colorectal adenocarcinoma (HT29), and hepatoblastoma (HepG2). The selective index (SI) was assessed on MRC5 (Normal human fetal lung fibroblast) cell line. The dichloromethane fraction (DCM) showed remarkable cytotoxic activity against MCF7 and HT29 (%Cell viability; 46.15 and 60.5, respectively). Hence, the main bioactive fraction from DCM was purified to afford two phytosterols; stigmasterol (1) and β-sitosterol (2), which were identified by 1-D and 2-D NMR spectroscopy. Cytotoxic evaluation of 1 and 2 revealed that β-sitosterol showed better selective cytotoxicity against MCF7 and HT29 (IC50 4.07 μg/mL, SI 2.63; IC50 4.52 μg/mL, SI 2.37) compared to stigmasterol (IC50 5.43 μg/mL, SI 1.38; IC50 4.21 μg/mL, SI 1.78), respectively. Bioinformatic assessments of drug-likeness and ADMET properties demonstrated that most criteria were obeyed by the investigated compounds except for their poor solubility, which recommended the preparation of special dosage forms, such as nanoformulation to enhance their oral bioavailability. Swiss Target prediction indicated that nuclear receptors represent the main target class (40%). Whereas caspase-3 stimulant activity (a key enzyme in apoptosis) was predicted by the PASS prediction tool as a potential anticancer mechanism. Our study suggests A. hispidum as a potential source of bioactive phytosterols and as a chemopreventive medicinal plant.

الملخص: أهداف البحث: داساتينيب هو مثبط تيروزين كيناز من الجيل الثاني. إنه يعمل كدواء جزيء صغير متعدد الأهداف من خلال استهداف كينازات التيروزين المختلفة التي تشارك في نمو الخلايا الورمية. وقد وجدت التحقيقات الأخيرة أنه يمنع تكاثر الخلايا السرطانية، والهجرة، ويحفز موت الخلايا المبرمج في مجموعة متنوعة من الأورام الصلبة. ومع ذلك، فهو ضعيف الذوبان في الماء تحت ظروف الرقم الهيدروجيني المختلفة، بالإضافة إلى نصف عمره القصير. لذلك، فإن تطوير نظام توصيل الدواء المحتوي على داساتينيب، ذاتي الاستحلاب يمكن أن يساعد في التغلب على هذه المشكلات في علاج الخلايا السرطانية. طريقة البحث: تم تطوير تركيبات مختلفة لنظام توصيل الدواء ذاتي الاستحلاب ومحملة بداساتينيب باستخدام آيزوبروبيل ميريستات (مرحلة الزيت)، ولابرافيل (الخافض للتوتر السطحي)، والبولي إيثيلين جلايكول (الخافض للتوتر السطحي المشترك). تم تقييم الخواص الفيزيائية والكيميائية للتركيبات من حيث حجم القطرات، وكفاءة التغليف، وإطلاق الدواء في المختبر. تم أيضا تقييم السمية الخلوية للتركيبات على ثلاثة خطوط من الخلايا السرطانية، وسرطان القولون والمستقيم البشري وسرطان الثدي الغدي البشري، بالإضافة إلى خلايا الليفية الرئوية الجنينية البشرية الطبيعية من أجل الانتقائية. النتائج: داساتينيب-تركيبة نظام توصيل الدواء ذاتي الاستحلاب، تتميز بحجم جسيم جيد، وكفاءة تغليف، وإطلاق دواء في المختبر. في فهمنا، أظهرت هذه الدراسة أن فعالية داساتينيب المضادة للسرطان - نظام الاستحلاب الذاتي، ونظام توصيل الدواء كان لها تأثيرات أفضل على السمية الخلوية على خطوط الخلايا السرطانية الثلاثة، وسرطان الثدي الغدي البشري، وسرطان القولون والمستقيم البشري، مقارنة مع داساتينيب النقي. الاستنتاجات: من المحتمل أن تكون تركيبات نظام توصيل الدواء داساتينيب-الاستحلاب الذاتي، فعالة كطريقة مستدامة لتوصيل الدواء لعلاج السرطان. Abstract: Background/Aim: Dasatinib (DS), a second-generation tyrosine kinase inhibitor, functions as a multi-target small-molecule drug via targeting various tyrosine kinases involved in neoplastic cell growth. DS inhibits cancer cell replication and migration, and induces tumor cell apoptosis in a variety of solid tumors. However, it is poorly soluble in water under some pH values. Therefore, the development of a DS-containing, self-emulsifying, drug delivery system (SeDDs) could help overcome these problems in treating cancer cells. Methods: Various SeDD formulations loaded with DS were developed with isopropyl myristate (oil phase), Labrafil (surfactant), and polyethylene glycol (co-surfactant). The physicochemical properties of the formulations were assessed according to droplet size, encapsulation efficiency, and in vitro drug release. The cytotoxicity of the formulations on the cancer cell lines HT29 and SW420 (human colorectal carcinoma), and MCF7 (human breast adenocarcinoma), in addition to MRC5 normal human fetal lung fibroblasts, was evaluated to assess selectivity. Results: The DS-SeDD formulation showed favorable particle size, encapsulation efficiency, and in vitro drug release. The anti-cancer potency of DS-SeDDs had greater cytotoxicity effects than pure DA on the three cancer cell lines, MCF7, HT29, and SW420l. Conclusion: The developed DS-SeDD formulations may potentially be an effective sustained drug delivery method for cancer therapy.

Abstract This study on Buddleja polystachya highlights its phytochemical composition, antimicrobial activity, and cytotoxic impacts. The study emphasizes the plant’s potential to treat ocular diseases by identifying important compounds involved in the bioactivity through GC-MS analysis. This study explores the antimicrobial and cytotoxic potential of Buddleja polystachya (stem and leaves) extracts, with a focus on their application in treating bacterial ocular infections and their efficacy against MCF7, HT29, and HepG2 cancer cells. Through comprehensive GC-MS analysis, a diverse array of phytochemicals was identified within Buddleja polystachya stem and leaves extracts, including carbohydrates, phenolic derivatives, fatty acids, and steroidal components. The extracts were then evaluated for their biological activities, revealing significant antimicrobial properties against a range of bacterial strains implicated in ocular infections. The research findings demonstrate that stem extracts derived from Buddleja polystachya demonstrated high to moderate cytotoxic effects on cancer cell lines MCF7, HT29, and HepG2. Notably, these effects were characterized by varying IC50 values, which suggest distinct levels of sensitivity. In contrast, leaf extracts exhibited reduced cytotoxicity when tested against all these cell lines, although they did so with a significantly higher cytotoxicity aganist HepG2 cells. The results of this investigation highlight the potential therapeutic utilization of Buddleja polystachya extracts in the management of ocular infections and cancer. These results support the need for additional research to elucidate the underlying mechanisms of action of these extracts and explore their potential as drugs.

Abstract The COVID-19 has had a significant influence on people's lives across the world. The viral genome has undergone numerous unanticipated changes that have given rise to new varieties, raising alarm on a global scale. Bioactive phytochemicals derived from nature and synthetic sources possess lot of potential as pathogenic virus inhibitors. The goal of the recent study is to report new inhibitors of Schiff bases of 1,3-dipheny urea derivatives against SARS COV-2 spike protein through in-vitro and in-silico approach. Total 14 compounds were evaluated, surprisingly, all the compounds showed strong inhibition with inhibitory values between 79.60% and 96.00% inhibition. Here, compounds 3a (96.00%), 3d (89.60%), 3e (84.30%), 3f (86.20%), 3g (88.30%), 3h (86.80%), 3k (82.10%), 3l (90.10%), 3m (93.49%), 3n (85.64%), and 3o (81.79%) exhibited high inhibitory potential against SARS COV-2 spike protein. While 3c also showed significant inhibitory potential with 79.60% inhibition. The molecular docking of these compounds revealed excellent fitting of molecules in the spike protein receptor binding domain (RBD) with good interactions with the key residues of RBD and docking scores ranging from − 4.73 to − 5.60 kcal/mol. Furthermore, molecular dynamics simulation for 150 ns indicated a strong stability of a complex 3a:6MOJ. These findings obtained from the in-vitro and in-silico study reflect higher potency of the Schiff bases of 1,3-diphenyl urea derivatives. Furthermore, also highlight their medicinal importance for the treatment of SARS COV-2 infection. Therefore, these small molecules could be a possible drug candidate.

BackgroundSocial determinants of health (SDOH), have been demonstrated to significantly impact health outcomes in spine patients. There may be interaction between opioid use and these factors in spine surgical patients. We aimed to evaluate the social determinants of health (SDOH) which are associated with perioperative opioid use among lumbar spine patients.MethodsThis retrospective cohort study included patients undergoing spine surgery for lumbar degeneration in 2019. Opioid use was determined based on prescription records from the electronic medical records. Preoperative opioid users (OU) were compared with opioid-naïve patients regarding SDOH including demographics like age and race, and clinical data such as activity and tobacco use. Demographics and surgical data, including age, comorbidities, surgical invasiveness, and other variables were also collected from the records. Multivariate logistic regression was used for analysis of these factors.ResultsNinety-eight patients were opioid-naïve and 90 used opioids preoperatively. All OU had ≥3 months of use, had more prior spine surgeries (1.07 vs. 0.44, p

Background: Edible fruits and resins provide various benefits to mankind including potential medicinal applications. This study aimed to determine the cytotoxicity, selectivity, and clonogenicity of fruits and exudates of certain Saudi medicinal plants (Anethum graveolens (BEP-09), Opuntia ficus-indica (L.) Miller (BEP-10), Boswellia serrata Roxb. ex Colebr. (BEP-11), and Commiphora myrrha (BEP-12)) against human liver adenocarcinoma (HepG2). Methods: Initial cytotoxicity and cell line selectivity against different cell lines were screened using MTT assay. The most promising extract was subjected to gas chromatography-mass spectrometry (GC-MS) analysis to determine the main phytoconstituents. Clonogenicity was checked for the most active extract. Results: The selected plants’ fruits and resins possess a significant cytotoxic activity estimated as IC50. The fruit of BEP-10 was found to be the most active extract against liver cancer cells (IC50 = 2.82) comparable to both doxorubicin (IC50 = 1.40) and camptothecin (IC50 = 1.11). It showed a selectivity index of 4.47 compared to the normal human foetal lung fibroblast (MRC5) cells. BEP-10 showed a dose-dependent clonogenic effect against HepG2 cells comparable to the effect of doxorubicin. The GC-MS chromatogram of BEP-10 extract revealed the presence of eight small polar molecules, representing 73% of the total identified compounds and the rest three molecules (27%) were non-polar constituents. The furan derivatives represent the chief components in BEP-10 (16.3%), while the aldehyde 5-(hydroxymethyl)-2-furancarboxaldehyde was found to be the main molecule (13.2%). Conclusion: The fruits of BEP-10 have a potential cytotoxic effect particularly against HepG2. The identified phytoconstituents in the tested plant extract might contribute to the investigated cytotoxic activity.

Abstract Until recently, the main pharmaceuticals used to control cholesterol and prevent cardiovascular disease (CVD) were statin-related drugs, known for their historical side effects. Therefore, there is growing interest in exploring alternatives, such as nutritional and dietary components, that could play a central role in CVD prevention. This review aims to provide a comprehensive understanding of how natural phytosterols found in various diets combat CVDs. We begin with a description of the overall approach, then we explore in detail the different direct and indirect mechanisms that contribute to reducing cardiovascular incidents. Phytosterols, including stigmasterol, β-sitosterol, ergosterol, and fucosterol, emerge as promising molecules within nutritional systems for protection against CVDs due to their beneficial effects at different levels through direct or indirect cellular, subcellular, and molecular mechanisms. Specifically, the mentioned phytosterols exhibit the ability to diminish the generation of various radicals, including hydroperoxides and hydrogen peroxide. They also promote the activation of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione, while inhibiting lipid peroxidation through the activation of Nrf2 and Nrf2/heme oxygenase-1 (HO-1) signaling pathways. Additionally, they demonstrate a significant inhibitory capacity in the generation of pro-inflammatory cytokines, thus playing a crucial role in regulating the inflammatory/immune response by inhibiting the expression of proteins involved in cellular signaling pathways such as JAK3/STAT3 and NF-κB. Moreover, phytosterols play a key role in reducing cholesterol absorption and improving the lipid profile. These compounds can be used as dietary supplements or included in specific diets to aid control cholesterol levels, particularly in individuals suffering from hypercholesterolemia. Graphical Abstract

Abstract Nod-like receptor protein 3 (NLRP-3), is an intracellular sensor that is involved in inflammasome activation, and the aberrant expression of NLRP3 is responsible for diabetes mellitus, its complications, and many other inflammatory diseases. NLRP3 is considered a promising drug target for novel drug design. Here, a pharmacophore model was generated from the most potent inhibitor, and its validation was performed by the Gunner-Henry scoring method. The validated pharmacophore was used to screen selected compounds databases. As a result, 646 compounds were mapped on the pharmacophore model. After applying Lipinski's rule of five, 391 hits were obtained. All the hits were docked into the binding pocket of target protein. Based on docking scores and interactions with binding site residues, six compounds were selected potential hits. To check the stability of these compounds, 100 ns molecular dynamic (MD) simulations were performed. The RMSD, RMSF, DCCM and hydrogen bond analysis showed that all the six compounds formed stable complex with NLRP3. The binding free energy with the MM-PBSA approach suggested that electrostatic force, and van der Waals interactions, played a significant role in the binding pattern of these compounds. Thus, the outcomes of the current study could provide insights into the identification of new potential NLRP3 inflammasome inhibitors against diabetes and its related disorders.

Abstract Lung cancer is a disease with a high mortality rate and it is the number one cause of cancer death globally. Approximately 12–14% of non-small cell lung cancers are caused by mutations in KRASG12C. The KRASG12C is one of the most prevalent mutants in lung cancer patients. KRAS was first considered undruggable. The sotorasib and adagrasib are the recently approved drugs that selectively target KRASG12C, and offer new treatment approaches to enhance patient outcomes however drug resistance frequently arises. Drug development is a challenging, expensive, and time-consuming process. Recently, machine-learning-based virtual screening are used for the development of new drugs. In this study, we performed machine-learning-based virtual screening followed by molecular docking, all atoms molecular dynamics simulation, and binding energy calculations for the identifications of new inhibitors against the KRASG12C mutant. In this study, four machine learning models including, random forest, k-nearest neighbors, Gaussian naïve Bayes, and support vector machine were used. By using an external dataset and 5-fold cross-validation, the developed models were validated. Among all the models the performance of the random forest (RF) model was best on the train/test dataset and external dataset. The random forest model was further used for the virtual screening of the ZINC15 database, in-house database, Pakistani phytochemicals, and South African Natural Products database. A total of 100 ns MD simulation was performed for the four best docking score complexes as well as the standard compound in complex with KRASG12C. Furthermore, the top four hits revealed greater stability and greater binding affinities for KRASG12C compared to the standard drug. These new hits have the potential to inhibit KRASG12C and may help to prevent KRAS-associated lung cancer. All the datasets used in this study can be freely available at ( https://github.com/Amar-Ajmal/Datasets-for-KRAS ).

The NOD-Like Receptor Protein-3 (NLRP3) inflammasome is a key therapeutic target for the treatment of epilepsy and has been reported to regulate inflammation in several neurological diseases. In this study, a machine learning-based virtual screening strategy has investigated candidate active compounds that inhibit the NLRP3 inflammasome. As machine learning-based virtual screening has the potential to accurately predict protein-ligand binding and reduce false positives outcomes compared to traditional virtual screening. Briefly, classification models were created using Support Vector Machine (SVM), Random Forest (RF), and K-Nearest Neighbor (KNN) machine learning methods. To determine the most crucial features of a molecule's activity, feature selection was carried out. By utilizing 10-fold cross-validation, the created models were analyzed. Among the generated models, the RF model obtained the best results as compared to others. Therefore, the RF model was used as a screening tool against the large chemical databases. Molecular operating environment (MOE) and PyRx software's were applied for molecular docking. Also, using the Amber Tools program, molecular dynamics (MD) simulation of potent inhibitors was carried out. The results showed that the KNN, SVM, and RF accuracy was 0.911 %, 0.906 %, and 0.946 %, respectively. Moreover, the model has shown sensitivity of 0.82 %, 0.78 %, and 0.86 % and specificity of 0.95 %, 0.96 %, and 0.98 % respectively. By applying the model to the ZINC and South African databases, we identified 98 and 39 compounds, respectively, potentially possessing anti-NLRP3 activity. Also, a molecular docking analysis produced ten ZINC and seven South African compounds that has comparable binding affinities to the reference drug. Moreover, MD analysis of the two complexes revealed that the two compounds (ZINC000009601348 and SANC00225) form stable complexes with varying amounts of binding energy. The in-silico studies indicate that both compounds most likely display their inhibitory effect by inhibiting the NLRP3 protein.

Colorectal cancer (CRC) is one of the most significant forms of human cancer. It is characterized by its heterogeneity because several molecular factors are involved in contiguity and can link it to others without having a linear correlation. Among the factors influencing tumor transformation in CRC, transforming growth factor-beta (TGF-β) plays a key promoter role. This factor is associated with human colorectal tumors with a very high prognosis: it increases the survival, invasion, and metastasis of CRC cells, thus functioning as an oncogene. The inhibition of this factor can constitute a major therapeutic route for CRC treatment. Various chemical drugs including synthetic molecules and biotherapies have been developed as TGF-β inhibitors. Moreover, the scientific community has recently shown a major interest in screening natural drugs inhibiting TGF-β in CRC. In this context, we carried out this review article using computerized databases, such as PubMed, Google Scholar, Springer Link, Science Direct, Cochrane Library, Embase, Web of Science, and Scopus, to highlight the molecular mechanism of TGF-β in CRC induction and progression and current advances in the pharmacodynamic effects of natural bioactive substances targeting TGF-β in CRC.

The development of natural substances derived from nature poses a significant challenge as technologies for the extraction and characterization of active principles advance. Hispolon has received a lot of attention in recent years, ascribable to its wide range of biological activities. It is a phenolic molecule that was extracted from several mushroom species such as Phellinus igniarius, Phellinus linteus, Phellinus lonicerinus, Phellinus merrillii, and Inonotus hispidus. To provide a comprehensive overview of the pharmacological activities of hispolon, this review highlights its anticancer, anti-inflammatory, antioxidant, antibacterial, and anti-diabetic activities. Several scientific research databases, including Google Scholar, Web of Science, PubMed, SciFinder, SpringerLink, Science Direct, Scopus, and, Wiley Online were used to gather the data on hispolon until May 2024. The in vitro and in vivo studies have revealed that hispolon exhibited significant anticancer properties through modifying several signaling pathways including cell apoptosis, cycle arrest, autophagy, and inhibition of angiogenesis and metastasis. Hispolon's antimicrobial activity was proven against many bacterial, fungal, and viral pathogens, highlighting its potential use as a novel antimicrobial agent. Additionally, hispolon displayed potent anti-inflammatory activity through the suppression of key inflammatory mediators, such as inducible NO synthase (iNOS), tumor necrosis factor-α (TNF-α), and cyclooxygenases-2 (COX-2), and the modulation of mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways. The antioxidant potential of hispolon was attributed to its capacity to neutralize reactive oxygen species (ROS) and to increase the activity of antioxidant enzymes, indicating a possible involvement in the prevention of oxidative stress-related illnesses. Hispolon's antidiabetic activity was associated with the inhibition of aldose reductase and α-glucosidase. Studies on hispolon emphasized its potential use as a promising scaffold for the development of novel therapeutic agents targeting various diseases, including cancer, infectious diseases, inflammatory disorders, and diabetes.

Background: Metastatic secondary ocular tumors spread from systemic malignancies, including breast cancer. This study aimed to evaluate the cytotoxicity of extracts from 5 medicinal plants native to Saudi Arabia. Methods: For preliminary activity screening, cytotoxicity using the MTT assay and selectivity index determinations were made for medicinal plant extracts against various cancer cell-lines. The most promising extract was subjected to GC-MS analysis to determine the phytochemical composition. Clonogenic assays were performed using the most promising extract to confirm the initial results. Finally, western blot analysis was used to determine the modulation in expression of survivin and P27 suppressor genes in the human breast adenocarcinoma (MCF7) cell-line to understand the potential mechanistic properties of the active plant extract. Results: The 5 plant extracts showed various cytotoxic activity levels using IC 50 . The most active extract was found to be the leaves of Capparis spinosa L. ( BEP-07 extract) against the MCF7 breast cancer cell-line (IC 50 = 3.61 ± 0.99 μg/ml) and selectivity index of 1.17 compared to the normal human fetal lung fibroblast (MRC5) cells. BEP-07 extract showed a dose dependent clonogenic effect against the MCF7 colonies which was comparable with the effect of doxorubicin. BEP-07 extract caused a significant decrease of survivin and increase in P27 expression compared to control GAPDH at its highest dose (14 µg/ml). The GC-MS chromatogram of Capparis spinosa L. ( BEP-07 extract) revealed the existence of 145 compounds, belonging to the diverse classes of phytoconstituents. Fatty acids and their derivatives represent 15.4%, whilst octadecanoic acid, 2,3-dihydroxypropyl ester was the principal component (7.9%) detected. Conclusion: Leaves of Capparis spinosa L. ( BEP-07 extract) exhibited a significant cytotoxic effect particularly against breast cancer cells. It exhibited this effect through survivin inhibition and via P27 upregulation. The detected phytoconstituents in the plant extract might be involved in tested cytotoxic activity, while further investigations are required to complete the drug candidate profile.

Oxidative stress results from a persistent imbalance in oxidation levels that promotes oxidants, playing a crucial role in the early and sustained phases of DNA damage and genomic and epigenetic instability, both of which are intricately linked to the development of tumors. The molecular pathways contributing to carcinogenesis in this context, particularly those related to double-strand and single-strand breaks in DNA, serve as indicators of DNA damage due to oxidation in cancer cases, as well as factors contributing to epigenetic instability through ectopic expressions. Oxidative stress has been considered a therapeutic target for many years, and an increasing number of studies have highlighted the promising effectiveness of natural products in cancer treatment. In this regard, we present significant research on the therapeutic targeting of oxidative stress using natural molecules and underscore the essential role of oxidative stress in cancer. The consequences of stress, especially epigenetic instability, also offer significant therapeutic prospects. In this context, the use of natural epi-drugs capable of modulating and reorganizing the epigenetic network is beginning to emerge remarkably. In this review, we emphasize the close connections between oxidative stress, epigenetic instability, and tumor transformation, while highlighting the role of natural substances as antioxidants and epi-drugs in the anti-tumoral context.

ABSTRACT: Background: There are many described techniques for the placement of posterior iliac screws for extension of lumbar posterior spinal instrumentation to the pelvis. However, each one has its limitations. We describe our technique for fluoroscopic guidance of iliac screw placement utilizing the obturator inlet and iliac oblique views as well as a detailed review of how to obtain and interpret these views for safe iliac screw placement. Methods: Retrospective chart review of patients undergoing iliac screw placement utilizing the obturator inlet and iliac oblique views as part of spine instrumentation between January 2019 and March 2022. Screw length and bony breaches are reported utilizing this technique. Results: Twelve patients underwent posterior lumbopelvic fixation with a total of 23 screws placed via either open or percutaneous technique. The mean screw length was 96.5 mm (Range 80–110, standard dev 7.75). There were no recorded breaches or recannulation attempts. Conclusions: We show how this technique is a much more convenient alternative to the placement of iliac screws under the obturator outlet oblique (“teardrop” view) which necessitates that the C-arm is in line with the instruments being placed. These described views can be used to place screws with either open or percutaneous techniques and with either the posterior superior iliac spine (PSIS) or S2 alar iliac (S2AI) starting points.

Abstract The quality of olive fruit (OF) is widely affected due to geographical variation, affecting OF's chemical composition and biological properties. It is a novel and first-time study to evaluate the quality variation of 42 olive samples from different geographical origins based on phytochemical profile and their biological activities. The study reports the presence of unique chemical markers responsible for the difference in quality and biological activity of the olive samples. Biological activity (cytotoxic and antimicrobial) with GCMS phytochemical profile was evaluated. GCMS analysis confirmed the presence of 111 volatile compounds from various chemical classes with range (%) and average (%): esters (21.61–60.49) and 44.62, alcohols (20.73–49.2) and 38.06, hydrocarbons (3–38.88) and 15.39, ketones (0.16–3.87) and 0.75, acids (0.07–2.62) and 0.27, and aldehydes (0.12–1.47) and 0.45. The predominant ester was 13-methyl-pentadecanoic acid methyl ester, a differentiation marker between these samples. Cytotoxicity assay showed a significant inhibitory effect against MCF7 (8–64%) and HCT116 (0.11–44%) cell lines, whereas the extracts with the highest cytotoxicity observed were O17 (52.00 ± 2.00) and O25 (64.00 ± 4.88). The antimicrobial activity exhibited a range of zones of inhibition (mm) against P. aeruginosa (0.00–17.00), E. coli (0.00–15.00), S. aureus (0.00–13), and resistant S. aureus, i.e., MRSA (0.00–12.00). The extracts with the highest antimicrobial activity, i.e., O8 and O39 had identical MIC and MBC of 12.5 and 25 µg/ml against P. aeruginosa. In contrast, an MIC (50 and 25) and MBC (100 and 50) against E. coli were determined for O39 and O8. The statistical PCA and K-mean cluster analysis (P

Plants belonging to the genus Prosopis L. (family Fabaceae, subfamily Mimosoideae) have gained significant popularity in traditional medicine due to their potential as anticancer, antidiabetic, anti-inflammatory, and antibacterial compounds. The primary objective of this work was to determine the phytochemical composition of the ethanolic extract derived from Prosopis juliflora leaves, as well as to assess its antibacterial and cytotoxic properties. The phytochemical screening using GC-MS revealed the presence of phytosteroids, ketone, esters, diisooctyl phthalate, and triterpenes. Besides, varying amounts of some silicon derivatives, which were reported to have antimicrobial activity, were detected with octasiloxane, which showed the highest amount (18.47%). 6-Ethoxy-6-methyl-2-cyclohexenone (antioxidant, antidiabetic, antiobesity, and antimicrobial) was detected in considerable quantity. Cytotoxic activity was seen in human breast cancer (MCF-7), human ovary adenocarcinoma (A2780), and human colon adenocarcinoma (HT-29) cell lines, as well as in normal human fetal lung fibroblasts (MRC-5), when subjected to the MTT assay. The plant extract exhibited the highest level of activity (5.75 μg/mL) against the A2780 cell line, with the MCF-7 cell line showing a somewhat lower level of activity (18.49 μg/mL). The antibacterial effect of the plant extracts was evaluated against four standard Gram-positive and four standard Gram-negative. The antimicrobial potential was observed only against Staphylococcus aureus which recorded a 14.5 ± 0.05 mm inhibition zone. The present study has demonstrated the identification of bioactive constituents in P. juliflora plant extracts, which exhibit significant cytotoxic activity against breast and colon malignancies. The study also highlighted P. juliflora extract as an antibacterial against S. aureus.

Acanthospermum hispidum DC. is a plant with extensive traditional use in folk medicine for treatment of various infections in Sudan including jaundice, stomach discomfort, constipation, and viral infections. This research was carried out to explore the biological and chemical properties of the crude extract of A. hispidum. Ethanol crude extract was prepared from the aerial parts of the plant and investigated for antibacterial action against standard monoderm and diderm bacteria using the cup plate method. Free radical scavenging was investigated out by using the DPPH method. Cytotoxicity assay was performed against human breast cancer cell line MCF7 using the MTT assay. Bioactive compounds were identified using GC-MS. The ethanolic extract of A. hispidum revealed antibacterial activity against all the tested bacteria. Also, the extract exhibited potent antioxidant activity at 0.5 mg/ml using DPPH (83% ± 00.09). The cytotoxicity against MCF7 revealed potent growth inhibition activity (IC50 75.8 µg/ml). GC-MS analysis revealed the presence of ethyl α-d-glucopyranoside, hexadecanoic acid, stigmasterol, β-sitosterol, undecanoic acid, phytol, alloaromadendrene oxide, 3-cyclopentylpropionic acid, 2-dimethylaminoethyl ester, and longifolenaldehyde in aerial parts of A. hispidum, all of which support antibacterial, antioxidant, and cytotoxic properties.

Cyanobacteria and microalgae contain various phytochemicals, including bioactive components in the form of secondary metabolites, namely flavonoids, phenolic acids, terpenoids, and tannins, with remarkable anticancer effects. This review highlights the recent advances in bioactive compounds, with potential anticancer activity, produced by cyanobacteria and microalgae. Previous in vitro investigations showed that many of these bioactive compounds exhibit potent effects against different human cancer types, such as leukemia and breast cancers. Multiple mechanisms implicated in the antitumor effect of these compounds were elucidated, including their ability to target cellular, subcellular, and molecular checkpoints linked to cancer development and promotion. Recent findings have highlighted various mechanisms of action of bioactive compounds produced by cyanobacteria and microalgae, including induction of autophagy and apoptosis, inhibition of telomerase and protein kinases, as well as modulation of epigenetic modifications. In vivo investigations have demonstrated a potent anti-angiogenesis effect on solid tumors, as well as a reduction in tumor volume. Some of these compounds were examined in clinical investigations for certain types of cancers, making them potent candidates/scaffolds for antitumor drug development.