Unraveling the therapeutic potential of Satureja nabateorum extract: inducing apoptosis and cell cycle arrest through p53, Bax/Bcl-2, and caspase-3 pathways in human malignant cell lines, with in silico insights.

Satureja nabateorum, known as Nabatean savory is a Lamiaceae plant native to the Arabian Peninsula, specifically in the mountainous regions of Saudi Arabia. The study aims to investigate the phytochemical components of the S. nabateorum leaves (SNL) and stems (SNS) extract and to assess their antioxidant, antimicrobial, and antiproliferative properties. Methanol extracts from leaves and stems were analyzed for chemical constituents using the GC-MS technique. Antioxidant capacities were measured using hydrogen peroxide and ABTS radical-scavenging methods, and antimicrobial activity was tested against various microorganisms. Cytotoxic activity on four human malignant cell lines was assessed using MTT and flow cytometry. Molecular docking and molecular dynamics studies were conducted to understand the interactions and binding modes of the extracted compounds at a molecular level. GC-MS analysis of SNL extract revealed thymol, carvacrol, and p-cymen-8-ol as major constituents. SNS extract contained ß-sitosterol, stigmasterol, lupeol, and lup-20(29)-ene-3ß,28-diol. SNS extract exhibited more potent antioxidant, antimicrobial, and anticancer effects than SNL extract. The extract, SNS, exhibited potential toxicity in A549 cells with an IC50 value of 3.62 µg/mL and induced marked apoptotic effects with S phase-cell cycle arrest. SNS extract also showed higher levels of Caspase 3, Bax, p53, and the Bax/Bcl2 ratio and lower levels of Bcl-2. Molecular docking and dynamic simulation supported these findings, targeting the EGFR TK domain. The study suggests that the S. nabateorum stem extract holds promise as a potent antimicrobial, antioxidant, and anticancer agent. It provides valuable insights for considering the extract as a substitute for chemotherapy and/or protective agents.

Chemical composition, antioxidant, and enzyme inhibition activities of Crithmum maritimum essential oils: the first chemo-biological study for species grown in North Africa.

Crithmum maritimum (sea fennel), is a halophytic plant species found globally in coastal environments. This study is the first investigation into the chemical composition and biological activities of C. maritimum growing wildly in Jebel Akhdar, Libya. Gas Chromatography-Mass Spectrometry (GC-MS) analysis was utilized to identify and profile the plant's volatile components; it resulted in the identification of twenty-four components, representing 99.17% of the total peaks in the GC-MS chromatogram. The analysis revealed that thymyl methyl ether, γ-terpinene, and ledene oxide, were the major volatile constituents of the plant at relative percentage levels of 56.86, 16.17, and 4.32%, respectively. The analysis also indicated substantial variations in the volatile composition of C. maritimum Libyan species compared to those from various geographic regions. The plant's volatile oil quality was evaluated by investigating its in vitro antioxidant activity and the oil's ability to inhibit acetylcholinesterase (AChE) and tyrosinase enzymes. The oil markedly scavenged the free radicals and reduced the ferric ions in the DPPH and FRAP assays at levels of 34.30 ± 0.10 and 38.90 ± 0.51 Trolox equivalents, respectively. The plant's volatile oil has substantially reduced the AChE at the IC50 value of 34.43 ± 0.25 compared to its effect against tyrosinase (IC50 12.449 ± 0.68). The in silico approach was used to highlight the mechanisms underlying the enzyme inhibitory effect of the plant volatile oil. The stigmastene and γ-santonin demonstrate stronger binding affinity towards AChE and tyrosinase compared to the co-crystalized controls, donepezil and tropolone. The study provides significant information for the environmental changes effect on the volatile constituents of C. maritimum and highlights the plant's importance within the scope of its antioxidant and enzyme inhibition activities.

Promising antibiofilm formation: Liquid phase pulsed laser ablation synthesis of Graphene Oxide@Platinum core-shell nanoparticles.

The increasing prevalence of multi-drug resistance in pathogenic bacteria has rendered antibiotics ineffective, necessitating the exploration of alternative antibacterial approaches. Consequently, research efforts have shifted towards developing new antibiotics and improving the efficacy of existing ones. In the present study, novel core shell graphene oxide@platinum nanoparticles (GRO@Pt-NPs) and their unchanging form have been synthesized using the two-step pulsed laser ablation in liquid (PLAL) technique. The first step involved using the graphene target to create graphene nanoparticles (GRO-NPs), followed by the ablation of GRO-NPs inside platinum nanoparticles (Pt-NPs). To characterize the nanoparticles, various methods were employed, including UV-VIS, transmission electron microscopy (TEM), energy dispersive X-ray (EDX), mapping tests, and X-ray diffraction (XRD). The anti-bacterial and anti-biofilm properties of the nanoparticles were investigated. TEM data confirm the creation of GRO@Pt-NPs. The average particle size was 11 nm for GRO-NPs, 14 nm for Pt-NPs, and 26 nm for GRO@Pt-NPs. The results demonstrate that the created GRO@Pt-NPs have strong antibacterial properties. This pattern is mostly produced through the accumulation of GRO@Pt-NPs on the bacterial surface of Klebsiella pneumoniae (K. pneumoniae) and Enterococcus faecium (E. faecium). The inhibition zones against K. pneumoniae and E. faecium when GRO-NPs were used alone were found to be 11.80 mm and 11.50 mm, respectively. For Pt-NPs, the inhibition zones of E. faecium and K. pneumoniae were 20.50 mm and 16.50 mm, respectively. The utilization of GRO@Pt-NPs resulted in a significant increase in these values, with inhibitory rates of 25.50 mm for E. faecium and 20.45 mm for K. pneumoniae. The antibacterial results were more potent in the core-shell structure than the GRO-NPs alone or Pt-NPs alone. The current work uses, for the first time, a fast and effective technique to synthesize the GRO@Pt-NPs by PLAL method, and the preparation has high clinical potential for prospective use as an antibacterial agent.

Phytochemical, biological, and computational investigations of Ephedra alata Decne. growing in salinity conditions of Arabian Peninsula.

Ephedra alata Decne is a medicinal plant widely used in traditional medicine for the management of bronchial asthma and cancer. Phytochemical analysis and biological activities, including antioxidant and anticancer effects, were investigated in the current work as new findings for the plant E. alata, a species growing wildly in the marsh and saline environments of the central area of Saudi Arabia. The Ultra Pressure Liquid Chromatography coupled with Electron spray ionization-Quadropole-Time of flight (UPLC-ESI-Q-TOF) system was used for the phytochemical analysis of the plant constituents. In addition, Polyphenolic profiling including the total phenolic (TPC) and flavonoid (TFC) contents of the plant extracts were measured. Phenolic acids were found at the highest relative percentages among all the identified compounds and were measured at 66.07 mg GAE (Gallic acid equivalent). The UPLC analysis of the E. alata extract indicated the presence of chlorogenic acid, syringic acid, caffeic acid, vanillic acid, rosmarinic acid, umbelliferone, isorhoifolin, and apigenin at the highest relative percentages. Mineral analysis indicated that the microelement content of E. alata was relatively low, except for magnesium (Mg). In vitro antioxidant assays revealed the ability of the plant to scavenge DPPH free radicals, reduced molybdenum ions, and ferrous at levels of 14.63, 19.97, and 27.78 mg Trolox equivalents, respectively. The extract induced transition metal chelation at 31.36 mg EDTA equivalents. The extract induced cytotoxic effects against MDA-231 and A549 cell lines at IC50 levels of 25.31 and 39.81 µg/mL, respectively. The plant extract inhibited the colonization and migration of cancer cells as part of its potential anticancer effects. In addition, major E. alata constituents like isorhoifolin, chlorogenic acid, apigenin, and rosmarinic acid exhibited the lowest binding energy to the CAIX enzyme at - 8.41, - 6.64, - 6.32, and - 6.26 kcal/mol, respectively, compared to the binding energy (- 7.72 kcal/mol) of the co-crystallized ligand (Y0R). The docking results further supported the selection of the CAIX enzyme as a standard predictive therapeutic target, since it exhibited significant binding interactions with the major constituents of the plant.

Purified L-glutaminase effects against multidrug-resistant Pseudomonas aeruginosa in experimental vaginosis model: An immunological and histopathological observation.

The antimicrobial activity of crude and purified L-glutaminase (EC 3.5.1.2), obtained from Lactobacillus gasseri, was evaluated against multidrug-resistant Pseudomonas aeruginosa in the in vivo vaginosis condition. The L-glutaminase possessed significant antimicrobial and anti-biofilm formation activity against multi-drug resistance P. aeruginosa, which were confirmed in the BALBc rat vaginosis model, together with its effects on the immunological and histopathological aspects. The untreated animals showed heavy vaginitis, characterized by sub-epithelial edema and infiltration of mononuclear leukocytes, perivascular heavy inflammatory cells infiltration in the vaginal tissue, and moderate stromal edema. However, the L-glutaminase treatment exhibited no changes in vaginal tissue structure with normal appearance of the epithelium and lamina propria with marked repair of the vaginal section when compared with normal, uninfected, control group A. The immunomodulatory actions of the L-glutaminase were confirmed by observance of higher concentrations of tumor necrosis factor-γ (TNF-γ), and interleukin -12 (IL-12) in treated animals, while the interleukin-10 (IL-10) was higher in the infected, untreated animals' sera samples. Therefore, the L-glutaminase showed corrective and healing actions, which were observed through histopathological observations of the vaginal tissue. The investigations led to imply that L-glutaminase may have the potential to be an effective antimicrobial agent for preventing and inhibiting bacterial growth, as well as inhibiting the biofilm formation in the P. aeruginosa-originated vaginosis. The observations may be of promising value for future clinical use.

Design, classification, and adverse effects of NSAIDs: A review on recent advancements.

Inflammation is a hallmark of many diseases, including cancer, neurodegenerative diseases like Alzheimer's, type II diabetes, rheumatoid arthritis, and asthma. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been a cornerstone in the management of various inflammatory, pain, and fever-related conditions. As a result, NSAIDs have found their applications in new therapeutic areas. NSAIDs are known to act by inhibiting the cyclooxygenase (COX) pathway. In recent years, new strategies have been proposed to counter inflammation and develop safer COX inhibitors. This review discusses the design of new COX inhibitors, the derivatization of conventional NSAIDs, and their biological applications. The review also presents an integrated classification of NSAIDs incorporating both traditional chemical-based and function-based approaches, including a brief overview of the NSAIDs of natural origins. Additionally, the review addresses adverse effects associated with different NSAIDs, including effects associated with cardiovascular, renal, and hepatic complications emphasizing the need for the development of new and safer COX inhibitors.

The role of statins in amyotrophic lateral sclerosis: protective or not?

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of motor neurons characterized by muscle weakness, muscle twitching, and muscle wasting. ALS is regarded as the third-most frequent neurodegenerative disease, subsequent to Alzheimer's disease (AD) and Parkinson's disease (PD). The World Health Organization (WHO) in 2007 declared that prolonged use of statins may induce development of ALS-like syndrome and may increase ALS risk. Subsequently, different studies have implicated statins in the pathogenesis of ALS. In contrast, results from preclinical and clinical studies highlighted the protective role of statins against ALS neuropathology. Recently, meta-analyses and systematic reviews illustrated no association between long-term use of statins and ALS risk. These findings highlighted controversial points regarding the effects of statins on ALS pathogenesis and risk. The neuroprotective effects of statins against the development and progression of ALS may be mediated by regulating dyslipidemia and inflammatory changes. However, the mechanism for induction of ALS neuropathology by statins may be related to the dysregulation of liver X receptor signaling (LXR) signaling in the motor neurons and reduction of cholesterol, which has a neuroprotective effect against ALS neuropathology. Nevertheless, the exact role of statins on the pathogenesis of ALS was not fully elucidated. Therefore, this narrative review aims to discuss the role of statins in ALS neuropathology.

Targeting the PI3K/pAKT/mTOR/NF-κB/FOXO3a signaling pathway for suppressing the development of hepatocellular carcinoma in rats: Role of the natural remedic Suaeda vermiculata forssk.

Liver malignancy is well recognized as a prominent health concern, with numerous treatment options available. Natural products are considered a renewable source, providing inspiring chemical moieties that could be used for cancer treatment. Suaeda vermiculata Forssk has traditionally been employed for management of hepatic conditions, including liver inflammation, and liver cirrhosis, as well as to improve general liver function. The findings of our earlier study demonstrated encouraging in vivo hepatoprotective benefits against liver injury generated by paracetamol and carbon tetrachloride. Additionally, Suaeda vermiculata Forssk exhibited cytotoxic activities in vitro against Hep-G2 cell lines and cell lines resistant to doxorubicin. The present investigation aimed to examine the potential in vivo hepatoprotective efficacy of Suaeda vermiculata Forssk extract (SVE) against hepatocellular carcinoma induced by diethylnitrosamine (DENA) in rats. The potential involvement of the PI3K/AKT/mTOR/NF-κB pathway was addressed. Sixty adult male albino rats were allocated into five groups randomly (n = 10). First group received a buffer, whereas second group received SVE only, third group received DENA only, and fourth and fifth groups received high and low doses of SVE, respectively, in the presence of DENA. Liver toxicity and tumor markers (HGFR, p-AKT, PI3K, mTOR, NF-κB, FOXO3a), apoptosis markers, and histopathological changes were analyzed. The current results demonstrated that SVE inhibited PI3K/AKT/mTOR/NF-κB pathway as well as increased expression of apoptotic parameters and FOXO3a levels, which were deteriorated by DENA treatment. Furthermore, SVE improved liver toxicity markers and histopathological changes induced by DENA administration. This study provided evidence for the conventional hepatoprotective properties attributed to SV and investigated the underlying mechanism by which its extract, SVE, could potentially serve as a novel option for hepatocellular carcinoma (HCC) treatment derived from a natural source.

Antibacterial and hemocompatibility potentials of nano-gold-cored alginate preparation against anaerobic bacteria from acne vulgaris.

Acne is a prevalent dermatological disease, with high global incidence, and is a health menace. The current study aimed to isolate and characterize the anaerobic bacteria responsible for the condition. Causes of a total of 70 acne-based bacterium isolates obtained from patients of mild, moderate, and severe acne, 24 were Clostridium innocuum, 21 were Lactobacillus plantarum, 13 were Anaerococcus prevotii, and 12 were Peptoniphilus asaccharolyticus. Nearly 69% of males were suffering, while the rest were females at 31%. The 15-30 years old age group was the most affected. The gold/alginate nanoparticles' nanopreparation (GANPs) produced from chloroauric acid and sodium alginate was an effective treatment against the acne conditions under the experimental conditions. The nanopreparation exhibited significant inhibitory activity against anaerobic bacterial isolates, with a minimum inhibitory concentration of 200 µg/ml for A. prevotii and P. asaccharolyticus, and 400 µg/ml for C. innocuum and L. plantarum. The in vitro efficacy of the GANPs on human blood parameters was also assessed. The concurrent results suggested potential antibacterial activity and hemocompatibility of the product, which has promise to be used as a successful antibacterial agent for acne.

Defective autophagy and autophagy activators in myasthenia gravis: a rare entity and unusual scenario.

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction (NMJ) that results from autoantibodies against nicotinic acetylcholine receptors (nAchRs) at NMJs. These autoantibodies are mainly originated from autoreactive B cells that bind and destroy nAchRs at NMJs preventing nerve impulses from activating the end-plates of skeletal muscle. Indeed, immune dysregulation plays a crucial role in the pathogenesis of MG. Autoreactive B cells are increased in MG due to the defect in the central and peripheral tolerance mechanisms. As well, autoreactive T cells are augmented in MG due to the diversion of regulatory T (Treg) cells or a defect in thymic anergy leading to T cell-mediated autoimmunity. Furthermore, macroautophagy/autophagy, which is a conserved cellular catabolic process, plays a critical role in autoimmune diseases by regulating antigen presentation, survival of immune cells and cytokine-mediated inflammation. Abnormal autophagic flux is associated with different autoimmune disorders. Autophagy regulates the connection between innate and adaptive immune responses by controlling the production of cytokines and survival of Tregs. As autophagy is involved in autoimmune disorders, it may play a major role in the pathogenesis of MG. Therefore, this mini-review demonstrates the potential role of autophagy and autophagy activators in MG.Abbreviations: Ach, acetylcholine; Breg, regulatory B; IgG, immunoglobulin G; MG, myasthenia gravis; NMJ, neuromuscular junction; ROS, reactive oxygen species; Treg, regulatory T; Ubl, ubiquitin-like.

Liposome Nanocarriers Based on γ Oryzanol: Preparation, Characterization, and In Vivo Assessment of Toxicity and Antioxidant Activity.

The present study aimed to develop and characterize liposome nanocarriers based on γ oryzanol and evaluate their potential in vitro and in vivo toxicity and antioxidant effects. The liposomes were physicochemically characterized using various techniques, including dynamic light scattering (DLS) for size and polydispersity index (PDI) measurements and ζ-potential analysis. The in vitro toxicity assessments were performed using hemolysis and MTT assays on the HS5 cell line. In vivo, acute oral toxicity was evaluated by using LD50 assays in mice. Additionally, antioxidant activity was assessed through biochemical analysis of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and liver tissue catalase, malondialdehyde (MDA), and glutathione (GSH) levels. The results revealed that the liposomes exhibited a uniform and spherical morphology with suitable physicochemical properties for drug delivery applications. The in vitro cytotoxicity and hemolysis assays and the in vivo LD50 experiment indicated the potential safety of γ oryzanol liposomes, especially at lower concentrations. In addition, the assessment of liver enzymes, i.e., ALT and AST, and the antioxidant markers further revealed the safety of the formulation, particularly for the liver as a highly sensitive soft organ. Overall, the liposome nanocarriers based on γ oryzanol were successfully formulated and expressed potential safety, supporting their application for the purposes of drug delivery and therapeutic interventions, particularly for hepatocellular and antioxidant therapies; however, further investigations for preclinical and clinical studies could be the future prospects for liposome nanocarriers based on γ oryzanol to explore the safety and efficacy of these nanocarriers in various disease models and clinical settings.

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.

Anti-microbial efficacy of L-glutaminase (EC 3.5.1.2) against multidrug-resistant Pseudomonas aeruginosa infection.

The aims of this study were isolation-purification and characterization of L-glutaminase from L. gasseri BRLHM clinical isolates and investigation of its efficiency as an antimicrobial agent against multidrug-resistant P. aeruginosa. The MICs of L-glutaminase and gentamicin reference were evaluated by the well-diffusion method. The biofilm on the IUD contraceptive was visualized using atomic force microscopy (AFM) image analyses. The purified L-glutaminase possessed significant antimicrobial activity against P. aeruginosa isolates (p < 0.05), and the antibiofilm formation activity of the purified L-glutaminase was stronger than the antibiofilm activity of the referral standard drug, gentamicin (P < 0.05), which were checked by the inhibition of the biofilm formation on the IUD contraceptive device. Investigations indicated that L-glutaminase may have a crucial role in future clinical applications.

A multidisciplinary approach to the antioxidant and hepatoprotective activities of Arbutus pavarii Pampan fruit; in vitro and in Vivo biological evaluations, and in silico investigations.

The Libyan Strawberry, Arbutus pavarii Pampan (ARB), is an endemic Jebel Akhdar plant used for traditional medicine. This study presents the antioxidant and hepatoprotective properties of ARB fruit-extract. ARB phytochemical analysis indicated the presence of 354.54 GAE and 36.2 RE of the phenolics and flavonoids. LC-MS analysis identified 35 compounds belonging to phenolic acids, procyanidins, and flavonoid glycosides. Gallic acid, procyanidin dimer B3, ß-type procyanidin trimer C, and quercetin-3-O-glucoside were the major constituents of the plant extract. ARB administration to paracetamol (PAR)-intoxicated rats reduced serum ALT, AST, bilirubin, hepatic tissue MDA and proinflammatory markers; TNF-α and IL-6 with an increase in tissue GSH level and SOD activity. Histological and immunohistochemical studies revealed that ARB restored the liver histology and significantly reduced the tissue expression of caspase 3, IL-1B, and NF-KB in PAR-induced liver damage. Docking analysis disclosed good binding affinities of some compounds with XO, COX-1, 5-LOX, and PI3K.

Polyphenol Fingerprint, Biological Activities, and In Silico Studies of the Medicinal Plant Cistus parviflorus L. Extract.

Cistus parviflorus L. (Cistaceae) is a medicinal plant with several folkloric applications, including being used for urinary tract infections and as a food additive. In this study, the polyphenolic diversity and the antioxidant, antidiabetic, and antimicrobial activities of the C. parviflorus methanolic extract were evaluated. Spectrophotometric and HPLC-based analyses using standard polyphenolic compounds were conducted to measure the phenolics and flavonoids in the plant extract. The in vitro DPPH, ORAC, FRAP, and α-glucosidase assays were used to evaluate the plant's antioxidant and antidiabetic activities. Furthermore, disc diffusion and MIC-based microdilution tests were applied to evaluate the antimicrobial activity of the plant against broad-spectrum microorganisms. The analysis revealed the existence of high phenolic and flavonoid quantities that were measured at 302.59 ± 0.6 µg GAE and 134.3 ± 0.5 µg RE, respectively. The HPLC-based analysis revealed the existence of 18 phenolic acids and 8 flavonoids. The major phenolic acid was ellagic acid (169.03 ppm), while catechin was the major flavonoid (91.80 ppm). Remarkable antioxidant activity was measured using three different assays: DPPH, ORAC, and FRAP. Furthermore, strong inhibition of α-glucosidase compared to acarbose was recorded for the plant extract (IC50 0.924 ± 0.6). The results showed that C. parviflorus's extract had a strong anti-Escherichia coli effect with MIC value of 0.98 µg\mL and IZD value of 32.2 ± 0.58 mm compared to 25.3 ± 0.18 mm for gentamycin, the positive control. Moreover, Aspergillus niger, Aspergillus fumigatus, Staphylococcus aureus, Streptococcus pyogenes, and Salmonella typhimurium all showed significant growth inhibition in response to the extract, a result that may be related to the use of the plant in traditional medicine to treat urinary tract infections. The docking study indicated the higher binding affinity of the major identified compounds, i.e., ellagic acid, rutin, naringin, catechin, and punicalagin, to the S. aureus gyrase-DNA complex, which might suggest the possible mechanisms of the plant as antimicrobial agents.

A novel facile synthesis of metal nitride@metal oxide (BN/Gd2O3) nanocomposite and their antibacterial and anticancer activities.

In this study, a novel core/shell nanocomposite structure (h-BN@Gd2O3 NCs) was created for the first time by combining hexagonal boron nitride (h-BN) with doped gadolinium oxide (Gd2O3) using different laser pulse numbers, i.e., 150, 338, and 772 pulses. We employed various analytical techniques, including mapping analysis, FE-SEM, EDS, HRTEM, SAED, XRD, zeta potential analysis, DLS, FTIR, Raman spectroscopy, and PL measurements, to characterize the synthesized h-BN, c-Gd2O3, and h-BN@Gd2O3 NCs (338 pulses). XRD results indicated hexagonal and cubic crystal structures for BN and Gd2O3, respectively, while EDS confirmed their chemical composition and elemental mapping. Chemical bonds between B-N-Gd, B-N-O, and Gd-O bands at 412, 455, 474, and 520 cm-1 were identified by FTIR analysis. The antimicrobial and anticancer activities of these NCs using agar well diffusion and MTT assays. They exhibited potent antibacterial properties against both Gram-positive and Gram-negative pathogens. Furthermore, NCs have reduced the proliferation of cancerous cells, i.e., human colon adenocarcinoma cells (HT-29) and human breast cancer cells (MCF-7), while not affecting the proliferation of the normal breast cell line (MCF-10). The anticancer efficacy of NCs was validated by the AO/EtBr assay, which confirmed apoptotic cell death. Blood compatibility on human erythrocytes was also confirmed by hemolytic and in vitro toxicity assessments. The compiled results of the study proposed these nanoparticles could be used as a promising drug delivery system and potentially in healthcare applications.

Silver-cored Ziziphus spina-christi extract-loaded antimicrobial nanosuspension: overcoming multidrug resistance.

Aims: To synthesize a silver-cored nanosuspension utilizing Ziziphus spina-christi fresh-leaf extract and evaluate their antimicrobial activity against multidrug-resistant pathogenic microbes. Materials and Methods: The prepared nanosuspension was analyzed by spectro-analytical techniques and tested for antimicrobial activity and resistance to biofilm formation. The leaf extract and nanosuspension were tested separately and together as a mixture. Results: Constituent nanoparticles were average-sized (∼34 nm) and were active against both Gram-positive and Gram-negative microbes and yeast. Candida albicans showed a 24.50 ± 1.50 mm inhibition zone, followed by Escherichia coli and Staphylococcus aureus. Increased bioactivity with the highest multifold increments, 150%, for erythromycin against all tested microbes was observed. Carbenicillin and trimethoprim showed 166%- and 300%-fold increments for antimicrobial activity against Pseudomonas aeruginosa, respectively. Conclusion: The nanosuspension exhibited strong potential as an antimicrobial agent and overcame multidrug resistance.

Ziziphus spina-christi leaf extract-coated silver nanoparticles were synthesized using an environment-friendly method, and the preparation was effective against Escherichia coli, Staphylococcus aureus and Candida albicans. The prepared formulation showed increased antimicrobial activity at a 150­300% increase compared with leaf extract-only activity. The prepared suspension was also active against Pseudomonas aeruginosa, the multidrug-resistant microbe, and has the potential to treat drug-resistant microbial infections.

Involvement of PI3K/HIF-1α/c-MYC/iNOS Pathway in the Anticancer Effect of Suaeda vermiculata in Rats.

Suaeda vermiculata Forssk. ex JF Gmel. (SV), a traditional known plant, has shown in vitro cytotoxic activity against HepG2 and HepG-2/ADR (doxorubicin-resistant cells) liver cell carcinoma cell lines, as well as hepatoprotection against paracetamol and carbon tetrachloride (CCl4)-induced liver injury. The current study evaluated the protective effect of SV, administered against N-diethylnitrosamine (NDEA)-induced HCC in rats. The possible modulatory effect of SV on the PI3K/HIF-1α/c-MYC/iNOS pathway was investigated. Sixty male adult albino rats (200 ± 10 g) were equally classified into five groups. Group I served as a control; Group 2 (SV control group) received SV (p.o., 200 mg/kg body weight); Group 3 (NDEA-administered rats) received freshly prepared NDEA solution (100 mg/L); and Groups 4 and 5 received simultaneously, for 16 weeks, NDEA + SV extract (100 and 200 mg/kg, orally). NDEA-treated rats displayed significant increases in serum levels of AFP, CEA, PI3K, malondialdehyde (MDA), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGFR), with increased liver tissue protein expression of fibrinogen concomitant and significantly decreased concentrations of antioxidant parameters (catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH)) in comparison to normal rats. On the flip side, AFP, CEA, PI3K, MDA, EGFR, and VEGFR serum levels were significantly reduced in rats that received NDEA with SV, both at low (SV LD) and high (SV HD) doses, accompanied by significant improvements in antioxidant parameters compared to the NDEA-treated group. Conclusions: SV possesses a significant hepatoprotective effect against NDEA-induced HCC via inhibiting the PI3K/HIF-1α/c-MYC/iNOS pathway, suggesting that SV could be a promising hepatocellular carcinoma treatment.

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.