As part of efforts to identify natural modulators of multi-drug-resistant breast cancer, Euphorbia mauritanica L. chloroform extract yielded four undescribed oxygenated diterpenes, including three nor-ent-abietanes, euphomauritanol C-E (1-3), and one polyacylated jatrophane, euphomauritanolide A (4), along with two knowns, helioscopinolide A (5) and enukokurin (6). The chemical structures and configurations of compounds were established by combination of HRMS, FTIR, and NMR spectroscopic tools along with experimental and calculated TDDFT-ECD. The cytotoxicity evaluation of isolated compounds against the MCF-7ADR revealed 4 and 2 are the most potent with IC50 values of 3.2 ± 0.58 and 4.67 ± 0.29 μM, respectively. Co-administration of compounds 4 and 2 with DOX improved its cytotoxic effect, with a combination index value of 0.41 for 4, indicating a synergistic effect. Mechanistically, 4 modulated DOX anticancer properties via potentiating DOX-induced Go/G1 cell cycle arrest rather than G2M arrest of DOX alone and shifting the cell death of DOX to be mainly apoptotic cell death. Furthermore, 4 alone and combined with DOX showed promising anti-migratory effects against MCF-7ADR. In conclusion, 4 showed promising co-chemotherapeutic effects to the DOX against MCF-7ADR, indicating that this compound possesses potential as an auspicious lead chemical to target breast cancer cells resistant to doxorubicin.

The current study describes the isolation of exopolysaccharide (EPS) producing lactic acid bacteria (LAB) from marine samples and testing different sugar additives with different proportions for enhanced EPS yield. The isolate MSD8 showed the most potential, yielding 200 mg/L of EPS after being cultivated at 37 °C for 48 h on de Man Rogosa and Sharpe medium (MRS) supplemented with 3% sucrose. The marine isolate MSD8 was identified as Enterococcus faecium with 99.58% probability using 16S rRNA gene sequencing. The obtained sequence was deposited in GenBank and assigned the accession number MW924065. The feature of MSD8-EPS was characterized by estimating the total carbohydrate content by UV-vis to be ~ 71%. The FTIR analysis further indicated the presence of characteristic bands of polysaccharide. The cytotoxicity of the produced MSD8-EPS was assessed using human skin fibroblasts (HSF). The IC50 was determined to be > 100 μg/mL, which signifies that MSD8-EPS is safe for skin application. The produced EPS was used to prepare a novel ointment, which was tested for wound healing ability in male albino rats. The ointment significantly (P ≤ 0.05) shortened the time needed for wound healing, as it successfully healed the wounds by 94.93% on the 7th day and completely (100%) healed the wound by the 12th day. In comparison, the control group was healed by 73.2% and 84.83%, respectively. The data confirm that the prepared ointment can safely be used for pharmaceutical wound care products.

Staphyloxanthin (STX) is a secondary metabolite pigment associated with membrane structures, recognized for its significant antioxidant properties. It plays a crucial role in combating reactive oxygen species (ROS), positioning it as a promising and effective alternative in cancer treatment. This study focused on enhancing the production of STX pigment by employing statistical optimization of media components, alongside the evaluation of its safety and anticancer properties.

A total of 59 Staphylococcus aureus isolates were screened and quantitatively estimated for STX production. The best pigment-producing isolate was identified based on molecular phylogenetic analysis as S. aureus A2, with accession number PP197164. A Box-Wilson central composite design was employed to evaluate the intricate interactions among six variables affecting the pigment yield. The most optimal conditions resulted in the highest production of STX of OD456 = 0.328, which is approximately 1.5-fold greater than the yield (OD456 = 0.215) obtained from OFAT optimization. The final response surface model fitting the data achieved a R² of 0.8748. STX exhibited marked cytotoxicity against the A549 NSCLC cell line with IC50 of 57.3 µg/mL, a safe dose in normal Vero cells. The anticancer activity of STX was predominantly mediated by the apoptotic pathway, as confirmed by confocal microscopy, the annexin V-FITC apoptosis assay, and the overexpression of caspase-3. Moreover, STX disrupted cell cycle at pre-G1 and G0/G1 phases in lung cancer. Intriguingly, STX exhibited its antitumor activity through reducing the EGFR expression. The molecular docking study revealed the potential binding interactions and affinities within the active sites of both wild-type and mutant EGFR.

The bioprocess for optimized production, combined with the biological profiling and low cytotoxicity, substantiates the potential application of STX pigment in combating lung cancer.

One of the main causes of death worldwide is cancer, a disorder in which a solid or liquid mass of cells known as a tumor develops when one or more cells lose the capacity to regulate their development. This study aims to assess the potential of chitosan as an anticancer agent in place of standard therapy regimens that have some degree of unselective cytotoxicity. PCR was performed for the RNA extraction of Caspase-3 and β-actin genes, and Cq values and quantification curves for each gene were recorded. Additionally, SRB and FITC apoptosis investigations were used to assess the effectiveness of chitosan powder's anticancer activity against breast cancer cells.

A significant challenge in cancer treatment is the rising problem of drug resistance that reduces the effectiveness of therapeutic strategies. Current knowledge shows that multiple mechanisms play a role in cancer drug resistance. Another mechanism that has gained attention is the alteration in sphingolipid trafficking and the dysregulation of its metabolism, which was reported to cause cancer-associated drug resistance. Sphingolipids are lipids containing sphingosine and have multiple roles, ranging from lipid raft formation, apoptosis, and cell signaling to immune cell trafficking. Recent studies show that in developing cancer cells, altered or dysregulated sphingolipids are associated with drug efflux and promote the survival of cancer cells by bypassing apoptosis. Upregulated levels of the glucosylceramide synthase (GCS), an enzyme that functions in sphingolipid metabolism, lead to the upregulated ABCB1 gene that induces drug efflux from the cancer cells. These bypass mechanisms make drugs that induce apoptosis in tumor cells ineffective. By highlighting the current findings, this review aims to provide a mechanism of drug resistance caused by the dysregulation of glucosylceramide synthase, sphingosine kinase, and acid ceramidase enzymes as possible therapeutic targets to enhance the effectiveness of the currently used chemotherapeutic agents.

Hepatic cancer, one of the most prevalent and lethal cancers globally, remains a significant health challenge, with limited treatment options underscoring the urgent need for novel, more effective therapies. Yttrium oxide nanoparticles (Y2O3 NPs) have attracted attention in nanomedicine due to their promising properties, including enhanced drug delivery, imaging capabilities, and therapeutic effects. However, the specific impact of Y2O3 NPs on hepatic cancer is largely unexplored. Therefore, this study was conducted to assess the cytotoxic effects of Y2O3 NPs on cell viability, reactive oxygen species (ROS) generation, genomic stability, mitochondrial integrity, and apoptosis induction in Hep-G2 hepatic cancer cells. The results from the SRB cytotoxicity assay demonstrated a strong concentration-dependent decrease in Hep-G2 cell viability, with a notably low half-maximal inhibitory concentration (IC50) value of 13.15 µg/ml. Exposure to the IC50 concentration of Y2O3 NPs led to increased ROS generation, DNA damage induction, and loss of mitochondrial membrane potential. Furthermore, the expression of pro-apoptotic p53 and mitochondrial ND3 genes was significantly upregulated, while the anti-apoptotic Bcl-2 gene was markedly downregulated, triggering apoptosis in Hep-G2 cells after 72 h of exposure to Y2O3 NPs. Collectively, these findings highlight the therapeutic potential of Y2O3 NPs in hepatic cancer, emphasizing the need for further research to fully explore their efficacy as a treatment option for liver cancer.

Gemcitabine hydrochloride (GEM) mimics one of the building blocks of DNA and RNA, so it indicates possible chemotherapeutic effects. It prevents cancer cells from producing DNA and proteins, which ultimately leads to their death. The goal of this work is to modify the GEM medication by nanoforming nanoliposomes based on the composition of Cholesterol, pectin nanoparticles, and phosphatidylcholine (PhC). The drug in nanoliposome form is made using the precipitation method, and several approaches are employed to characterize it. UV-Vis spectroscopy is used to measure the release process of GEM from the lipids and its integration with them. Results of the combination efficiency for PhC.Pectin@GEM, PhC.GEM@Pectin, and PhC@Cholestrol.GEM were recorded at 78.8 %, 83 %, and 80 %, respectively. A UV-Vis spectrophotometer was used to determine the release efficiency of the nanoliposomes, which was measured at pH values of 3, 6.8, and 7.4. The in-vitro investigation employed SRB (Routine analysis IC50) to determine the modified drug's toxicity on breast adenocarcinoma (MCF-7) cells, while the in-vitro study assessed the produced nanoliposomes' capacity to do so. The conclusion is that to ascertain whether GEM medicine's nanoliposomes can effectively treat breast cancer in place of GEM medication, clinical trials are necessary to prove the ability for treatment.

Corallocarpus glomeruliflorus (CGP), a plant native to Yemen, has been traditionally used for the management of various health conditions, including cancer, inflammation, and diabetes. This study presents the first comprehensive phytochemical and pharmacological investigation of CGP, revealing novel molecular mechanisms and therapeutic potential. Phytochemical analysis of the CGP extract revealed the presence of diverse bioactive compounds, including phenols, flavonoids, and other secondary metabolites. Notably, this is the first report identifying maritimetin, assafoetidin, kaempferol 3-rhamnoside 7-xyloside, and lespenefril in CGP, compounds with significant therapeutic potential. The total phenolic content was 88.12 ± 4.48 mg GAE/g, significantly higher than previously reported for related species (63.78 ± 1.27 mg GAE/g), and the total flavonoid content was 22.1 ± 0.01 mg QE/g. The extract demonstrated superior antimicrobial activity against Pseudomonas aeruginosa compared to previous studies, with a zone of inhibition of 16.7 ± 1.53 mm at 200 mg/mL concentration. The CGP extract displayed strong antioxidant activity in DPPH, FRAP, and phosphomolybdenum assays, with an IC50 value of 48.39 ± 1.58 μg/mL in the DPPH assay, compared to 9.88 ± 0.54 μg/mL for the positive control ascorbic acid. Most significantly, the CGP extract exhibited more potent selective anticancer effects on human breast (MCF-7) and colon (HCT-116) cancer cell lines than previously reported for related Cucurbitaceae species, with IC50 values of 49.18 ± 2.81 μg/mL and 244.2 ± 9.86 μg/mL, respectively. Our novel molecular docking studies revealed previously unreported interactions between CGP compounds and key therapeutic targets, particularly Pim-1, PIK3CA, α-amylase, and Gyr-B, providing new insights into its mechanism of action.

This study was performed to assess the use of chitosan (Cs) and zinc oxide nanocomposites ZnO NCP with full and half dose mebendazole (MBZ) during the muscular phases of Trichinella spiralis infection. Sixty Swiss Albino male mice were divided into six groups: G1 (negative control), G2 (positive control), G3 (MBZ at 200 mg/kg/day), G4 (Cs@MBZ NCP at 400 mg/kg/day), G5 (Cs@MBZ400.ZnO NCP), and G6 (Cs@MBZ200.ZnO NCP). Mice were infected orally with 200 T. spiralis larvae and received treatments starting on day 35 post-infection for five consecutive days. Treatment outcomes were evaluated by counting total muscular larvae, conducting blood biochemical measurements, and performing histopathological examinations of the liver and hip joint muscles. ELISA was used to measure serum levels of transforming growth factor-beta1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF). Results indicated that both Cs@MBZ400.ZnO NCP and Cs@MBZ200.ZnO NCP groups exhibited significant reductions in muscular larval counts (96.4 % and 96.1 %, respectively). Treated mice also showed reduced AST and ALT levels, increased total protein and albumin, and decreased globulin levels compared to positive controls. Cytokines levels of TNF-α, TGF-β1, and VEGF were lower in treated groups. Histopathological examination revealed that Cs@MBZ400.ZnO and Cs@MBZ200.ZnO NCP restored up to 90 % of normal tissue architecture. In conclusion, chitosan and zinc oxide nanocomposites enhanced the therapeutic ability of mebendazole against T. spiralis muscular stage as these nanocomposites had the highest effect on reducing parasite burden, improving blood biochemical, decreasing cytokines levels and restoring normal histological architecture.

Calcium titanate nanoparticles (CaTiO3NPs) have garnered significant attention due to their unique properties and excellent biocompatibility, which have led to their increased use in various fields and consumer products. This rise in application necessitates a better understanding of their biological and toxicological effects. However, there is limited data on the cytotoxicity and genotoxicity of CaTiO3NPs in human normal skin fibroblasts (HSF) and non-small lung cancer (A-549) cells. Consequently, this study aimed to explore the effect of 48-hour exposure to CaTiO3NPs on cell viability, genomic DNA integrity, and oxidative stress induction in human cancer A-549 cells, compared to normal HSF cells. The cytotoxicity and genotoxicity of CaTiO3NPs were assessed using the Sulforhodamine B (SRB) cytotoxicity and Alkaline Comet assays, respectively. To estimate possible oxidative stress induction and variation in apoptotic gene expression, reactive oxygen species (ROS) analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were also performed. Our findings demonstrated that exposure to CaTiO3NPs for 48 h resulted in low toxicity toward both normal HSF and cancer A-549 cells, with cell death observed only at high concentrations (100 and 1000 µg/ml). The IC50 value of CaTiO3NPs in both HSF and A-549 cells was greater than 1000 µg/ml; specifically, the IC50 value in A-549 cells at 48 h was 1670.65 µg /ml. However, treatment with CaTiO3NPs for 48 h at the IC50 concentration of 1670.65 µg /ml resulted in significant genomic DNA damage and excessive ROS generation, along with a notable disturbance in the expression level of apoptotic (p53 and Bax) and anti-apoptotic Bcl2 genes in A-549 cells. In contrast, no significant changes were observed in HSF cells treated for 48 h with the same concentration (1670.65 µg /ml) of CaTiO3NPs. Collectively, these findings indicated that despite short-term exposure to CaTiO3NPs causing low cytotoxicity in both normal HSF and A-549 cells. CaTiO3NPs were selectively genotoxic toward A-549 cells. This genotoxicity was mediated through excessive ROS generation, which disrupted genomic DNA integrity and altered the expression of apoptotic genes, triggering apoptosis in A-549 cells. Further in vitro and in vivo studies are needed to fully understand the toxicological and biological properties of CaTiO3NPs.

Obesity is a metabolic disease characterized by an imbalance between caloric intake and expenditure, leading to excess fat and increasing the risk of various health conditions. This study compares the anti-obesity effects of gold nanoparticles (AuNPs) to orlistat in an experimental model of induced obesity in Wistar Albino rats. In addition to negative and positive control rats, obese rats were treated with variable daily and weekly doses of AuNPs and daily orlistat for nine weeks. Bioelectric impedance analysis (BIA) and dissection techniques were used to indirectly and directly measure body-composition in all rat groups. Hepatic and renal function and ultrastructure were assessed by blood biochemical and histological examinations to detect treatment-related alterations. High doses of AuNPs reduced body fat, increased muscle mass, improved dyslipidemia, glycemia, and antioxidant effects in obese rats, and restored normal TG, FBG, and MDA levels by reducing obesity-related oxidative damage. Histological and ultrastructural examinations showed that these high doses repaired liver and kidney cells, and reduced fat accumulation and body weight compared to the standard treatment for obesity by orlistat.

Nowadays, researchers are attracted to the phyco-synthesis of selenium nanoparticles (SeNPs) for biotechnological and medical applications as they possess many advantages such as safety, nutritional value, and easy biodegradation than gold, copper, and silver nanoparticles. Spirulina platensis is the preferred microalgae for SeNPs synthesis because it contains many compounds that increase their stability making them fit for biomedical treatments.

The biosynthesized Spirulina platensis selenium nanoparticles (SP-SeNPs) were spherical and crystalline, with a diameter of 65 nm and a net charge of -16.7 mV. Furthermore, they were surrounded by active groups responsible for stability. The DPPH radical scavenging test assessed the antioxidant efficacy of SP-SeNPs and exposed scavenging inhibition of 79.234% at a 100 µM dosage. ABTS and H2O2 radical scavenging assay is dose-dependent recording IC50 of 50.69 and 116.18 µg/ml, respectively. The antibacterial efficacy was investigated against 13 G-negative & G-positive bacteria. The study demonstrated that SP-SeNPs had antibacterial and antibiofilm efficiencies against the tested strains with MBC of 286-333 µg/ml. The highest percentages of biofilm inhibition were recorded for Bacillus subtilis and Klebsiella pneumoniae, with ratios of 78.8 and 69.9%, respectively. The prepared SP-SeNPS efficiently suppressed the tested fungi growth with MIC (350 µg/ml) and MFCs (480-950 µg/ml). Most notably, biogenic SeNPs effectively extended the clot formation period recording 170.4 S for prothrombin time (PT) and 195.6 S for the activated partial thromboplastin time (aPTT). SP-SeNPs reduced the cell viability of breast adenocarcinoma (MCF-7) and ovarian cancer (SKOV-3) cell lines with a percentage of 17.6009% and 14.9484% at a concentration of 100 ug/ml, respectively. Moreover, SP-SeNPs could effectively alleviate the inflammation in RAW 264.7 macrophages with a reduction percentage of 8.82% in Nitric oxide concentration.

The investigation findings reveal that SP-SeNPs are a hopeful antimicrobial, anti-tumor, anticoagulant, antioxidant, and anti-inflammatory factor that can be applied in medical cures.

Background: Aging is a complex biological process characterized by the accumulation of molecular and cellular damage over time, often driven by oxidative stress. This oxidative stress is particularly detrimental to the testes, where it causes degeneration, reduced testosterone levels, and compromised fertility. D-galactose (D-gal) is commonly used to model aging as it induces oxidative stress, mimicking age-related cellular and molecular damage. Testicular aging is of significant concern due to its implications for reproductive health and hormonal balance. This research examines the protection by thymoquinone (TQ) or thymoquinone-loaded chitosan nanoparticles (NCPs) against D-galactose (D-gal)-induced aging in rat testes, focusing on biochemical, histological, and molecular changes. Aging, which is driven largely by oxidative stress, leads to significant testicular degeneration, reducing fertility. D-gal is widely used to model aging due to its ability to induce oxidative stress and mimic age-related damage. TQ, a bioactive ingredient of Nigella sativa, has earned a reputation for its anti-inflammatory, anti-apoptotic, and antioxidant characteristics, but its therapeutic application is limited by its poor bioavailability. Methods: Thymoquinone was loaded into chitosan nanoparticles (NCPs) to enhance its efficacy, and this was hypothesized to improve its stability and bioavailability. Four groups of male Wistar rats participated in the study: one for the control, one for D-gal, one for D-gal + TQ, and the last one for D-gal + NCP. Results: The results exhibited that D-gal substantially increased oxidative injury, reduced testosterone levels, and caused testicular damage. Treatment with TQ and NCPs significantly reduced oxidative stress, improved antioxidant enzyme levels, and restored testosterone levels, with NCPs showing a stronger protective effect than TQ alone. A histological analysis confirmed that NCPs better preserved testicular structure and function. Additionally, the NCP treatment upregulated the expression of key genes of oxidative stress resistance, mitochondrial function, and reproductive health, including SIRT1, FOXO3a, and TERT. Conclusions: The findings suggest that NCPs offer enhanced protection against aging-related testicular damage compared with TQ alone, which is likely due to the improved bioavailability and stability provided by the nanoparticle delivery system. This research emphasizes the potential of NCPs as a more effective therapeutic strategy for mitigating oxidative stress and age-related reproductive dysfunction. Future research should further explore the mechanisms underlying these protective effects.

Scientists have faced difficulties in synthesizing natural substances with potent biological activity from cost-effective sources. Endophytic fungi metabolites with nanoparticles have been utilized to develop a friendly, suitable procedure to address this problem and ameliorate the average amount of antioxidant, antimicrobial, and anticancer materials. Therefore, this study utilized endophytic fungi as a source of the natural extract with biosynthesized manganese nanoparticles (MnNPs) in the form of nanocomposites.

Thirty endophytic fungi were isolated and were assessed for their antioxidant activity by 1, 1-Diphenyl-2-picrylhydrazyl (DPPH) and antimicrobial activity. The most potent isolate was identified utilizing 18S rRNA and was applied to purify and separate their natural antimicrobial products by Flash column chromatography. In addition, the most potent product was identified based on instrumental analysis through Nuclear magnetic resonance (NMR), Fourier-transform infrared (FTIR), and Gas chromatography-mass spectrometry (GC.MS). The purified product was combined with biosynthsesized manganese nanoparticles (MnNPs) for the production of nanocomposite (MnNCs). Later on, the physicochemical features of MnNPs and its MnNCs were examined and then they were assessed for determination their biological activities.

The most potent isolate was identified as Aspergillus terreus with accession number OR243300. The antioxidant and antimicrobial product produced by the strain A. terreus was identified as an amide derivative consisting of 3-(2-Hydroxy-4,4-dimethyl-6-oxo-1-cyclohexen-1-yl)-4-oxopentanoic acid (HDOCOX) with the chemical formula C13H18O5. Furthermore, purified HDOCOX, MnNPs and Mn-HDOCOX-NPs nanocomposite (MnNCs) showed significant antimicrobial effectiveness. The minimum inhibitory concentrations (MICs) determined for MnNCs were 10 µg/mL against C. albicans and E.coli. Furthermore, MnNCs were reduced hepatocellular carcinoma viability.

The use of HDOCOX, either alone or in combination with MnNPs, is a potential candidate for inhibiting pathogenic microbes and the development of an anticancer drug pipeline.

The current study intends to reach the optimal use of plant wastes and explore their biological activities. It evaluated the bioactivities and phytoconstituents of 70 %methanol extract of Vicia faba L. peels. The results revealed that the extract possessed very potent cytotoxicity against ovarian cancer cell line (SKOV-3) (IC50=0.01 μg/mL) which exceeds doxorubicin (IC50=0.95 μg/ml), a reference anticancer agent, potent cytotoxicity against prostate cancer cell line (PC-3) (IC50=13.60 μg/ml), and moderate cytotoxicity against liver cancer cell line (HepG2) (IC50=40.9 μg/ml). Furthermore, the extract exhibited a potent antimicrobial effect on the tested gram-positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis& Micrococcus luteus) with inhibition zone (IZ) range (14.0-23.0 mm), gram-negative bacteria (Pseudomonas aeruginosa) (IZ=14.0 mm), and pathogenic fungal yeast (Candida albicans) (IZ=19.0 mm). Moreover, 46 phytoconstituents were tentatively identified using ultra-high-performance liquid chromatography (UHPLC) hyphenated with quadrupole-time-of-flight tandem mass spectrometry (QTOF-MS) in positive ionization mode, 21 phytoconstituents were detected in Vicia faba peel for the first time. High-performance liquid chromatography (HPLC) was used to quantify phenolic compounds, the major compounds were chlorogenic acid, ferulic acid, catechin, and vanillin. In conclusion, plant wastes are a rich source of phytoconstituents that exhibit biological efficacy.

Calcium hydroxide nanoparticles (Ca(OH)2NPs) possess potent antimicrobial activities and unique physical and chemical properties, making them valuable across various fields. However, limited information exists regarding their effects on genomic DNA integrity and their potential to induce apoptosis in normal and cancerous human cell lines. This study thus aimed to evaluate the impact of Ca(OH)2NPs on cell viability, genomic DNA integrity, and oxidative stress induction in human normal skin fibroblasts (HSF) and cancerous hepatic (HepG2) cells. Cell viability and genomic DNA stability were assessed using the Sulforhodamine B (SRB) assay and alkaline comet assay, respectively. Reactive oxygen species (ROS) levels were measured using 2,7-dichlorofluorescein diacetate, while the expression level of apoptosis-related genes (p53, Bax, and Bcl-2) were quantified using real-time PCR (qRT-PCR). The SRB cytotoxicity assay revealed that a 48-hour exposure to Ca(OH)2NPs caused concentration-dependent cell death and proliferation inhibition in both HSF and HepG2 cells, with IC50 values of 271.93 µg/mL for HSF and 291.8 µg/mL for HepG2 cells. Treatment with the IC50 concentration of Ca(OH)2NPs selectively induced significant DNA damage, excessive ROS generation, and marked dysregulation of apoptotic (p53 and Bax) and anti-apoptotic (Bcl-2) gene expression in HepG2 cells, triggering apoptosis. In contrast, exposure of HSF cells to the IC50 concentration of Ca(OH)2NPs caused no significant changes in genomic DNA integrity, ROS generation, or apoptotic gene expression. These findings indicate that Ca(OH)2NPs exhibit concentration-dependent cytotoxicity in both normal HSF and cancerous HepG2 cells. However, exposure to the IC50 concentration was non-genotoxic to normal HSF cells while selectively inducing genotoxicity and apoptosis in HepG2 cancer cells through DNA breaks and ROS-mediated mechanisms. Further studies are required to explore the biological and toxicological properties and therapeutic potential of Ca(OH)2NPs in hepatic cancer treatment.

Phyto-nanotechnology provides an eco-friendly approach for synthesizing biocompatible metal nanoparticles (NPs) with therapeutic potential. Lawsonia inermis (LI) has been historically valued for its diverse medicinal applications, especially its exceptional biological potency against various skin diseases, attributed to its rich abundance of bioactive compounds. Therefore, herein, plant-based iron and zinc NPs were biofabricated via sustainable and simple methods, using crude extracts of the aerial parts of LI as reducing, coating, and stabilizing agents. Since the extraction method affects the type of extracted phytocompounds, two extraction approaches─aqueous and hydro-alcoholic─were applied to determine the influence of the extraction route on the physicochemical and biological properties of the formed NPs. These properties were characterized via various analytical techniques and assays. The UV-Vis spectra revealed absorption bands ranging from 265 to 270 nm, while FT-IR confirmed the successful coating of the NPs with the extracts' phytochemicals, validating the biofabrication of the proposed NPs. The alcoholic-based NPs displayed higher total phenolic content, total flavonoid content, and antioxidant effect compared to their aqueous-based counterparts, reaching up to 55.13 μg of GAE/1 mg of dry weight (DW), 30.48 μg of QU/1 mg of DW, and IC50 of 46.02 μg/mL, respectively. All tested samples, except for Fe NPs, displayed significant cytotoxic effects against skin cancer, resulting in a cell viability as low as 1% at 1000 μg/mL. QTOF-LC/MS/MS analyses of LI extracts revealed tentative identification of more than 100 metabolites with phenolic compounds representing the largest share. Orthogonal Projections to Latent Structures Discriminant Analysis modeling revealed a clear separation between both extracts, with more than 40 marker compounds. The results indicated that both extracts were effective for the green synthesis of Fe and Zn NPs for biomedical applications, with the alcoholic extract of LI as a superior coating candidate and the aqueous extract as a stronger reducing agent. This work showcases the influence of extraction protocols on physicochemical and biological characteristics of the resulting nanoparticles.

Nanotherapy has emerged as a promising strategy for the targeted and efficient treatment of melanoma, the most aggressive and lethal form of skin cancer, with minimized systemic toxicity. However, the therapeutic efficacy of cobalt oxide nanoparticles (Co3O4NPs) in melanoma treatment remains unexplored. This study aimed to assess the therapeutic potential of Co3O4NPs in melanoma treatment by evaluating their impact on cell viability, genomic DNA and mitochondrial integrity, reactive oxygen species (ROS) generation and apoptosis induction in melanoma A-375 cells. Our findings demonstrated a concentration-dependent reduction in cell viability upon treatment with five Co3O4NP concentrations (0.2, 2, 20, 200, and 2000 µg/ml), with an IC50 value of 303.80 µg/ml. Treatment with this IC50 concentration significantly increased ROS generation, induced dramatic DNA damage, and disrupted mitochondrial membrane potential integrity. Flow cytometric analysis revealed apoptosis and necrosis induction following Co3O4NP exposure at the IC50 concentration value. Results of qRT-PCR analysis demonstrated remarkable dysregulation of apoptotic and mitochondrial genes, including a significant downregulation of apoptotic p53 and mitochondrial ND3 genes and marked upregulation of the anti-apoptotic gene Bcl2. These findings highlight the novel potential of Co3O4NPs as potent inducers of melanoma A-375 cell death in a concentration-dependent manner through excessive ROS production, genomic instability, mitochondrial dysfunction and dysregulation of apoptotic and mitochondrial gene expression, ultimately promoting apoptosis in A-375 cells. This study thus underscores the potential of Co3O4NPs as a promising nanotherapeutic candidate for melanoma treatment, warranting further exploration to elucidate their full biological and clinical applicability.

Ganoderma mushrooms have a variety of pharmacological activities and may have antitumor effects. Therefore, the antitumor activity of the methanolic fruiting body extracts of three Ganoderma spp. will be evaluated by estimating cell viability, cell cycle parameters and the mode of cellular death. In this regard, Sulfo-rhodamine B staining and flow cytometry were used. Hepatocellular carcinoma (HepG2) and breast ductal carcinoma (T-47D) cell lines were used as cancer models, while mouse normal liver (BNL) and oral epithelial cell (OEC) lines were used as respective controls. The results revealed that Ganoderma resinaceum extract decreased the viability of BNL at an IC50 > 100 µg/mL but not that of HepG2 at an IC50 of 72.32 µg/mL. Additionally, Ganoderma australe and Ganoderma mbrekobenum decreased the viability of OEC cell line at an IC50 of 328.29 and 271.56 µg/ mL, respectively. On the other hand, the IC50 of T-47D were 221.95 and 236.45 µg/mL, respectively. The three extracts arrested the cell life cycle at the G1 phase in each case. G. resinaceum extract stimulated total apoptosis (Q2 + Q4) of 19.99% with low necrosis (Q1). However, the percentages of total cell necrosis in the T-47D cell line treated with the other two extracts were 31.10% and 18.28%, respectively while the percentages of total cell apoptosis were 6.83% and 1.78%, respectively. Thus, G. resinaceum significantly inhibited the viability of the HepG2 cell line, while both the G. australe and G. mbrekobenum extracts significantly decreased the viability of the T-47D cell line. These results may encourage speculation about their possible use for the therapeutic management of hepatocellular carcinoma and breast ductal carcinoma after further investigation.

Yttrium oxide nanoparticles (Y2O3NPs) have emerged as a promising avenue for cancer therapy, primarily due to their distinctive properties that facilitate selective targeting of cancer cells. Despite their potential, the therapeutic effects of Y2O3NPs on human epidermoid skin cancer remain largely unexplored. This study was thus conducted to investigate the impact of Y2O3NPs on both human skin normal and cancer cells, with an emphasis on assessing their cytotoxicity, genotoxicity, and the mechanisms underlying these effects. Cell viability and apoptosis induction were assessed using the Sulforhodamine B and chromatin diffusion assay, respectively. Reactive oxygen species (ROS) level, mitochondrial membrane potential integrity, oxidative stress markers and expression level of apoptotic and mitochondrial genes were also estimated. Our findings highlight the selective and significant cytotoxicity of Y2O3NPs against human epidermoid A-431 cancer cells. Notably, exposure to five Y2O3NPs concentrations (0.1, 1, 10, 100 and 1000 µg/ml) resulted in a high concentration-dependent reduction in cell viability and a corresponding increase in cell death observed 72 h post-treatment specifically in A-431 cancer cells, while normal skin fibroblast (HSF) cells exhibited minimal toxicity. When A-431 cancer cells were treated with the half-maximal inhibitory concentration (IC50) of Y2O3NPs for 72 h, a significant increase in ROS generation was noted. This led to oxidative stress, along with severe damage to genomic DNA and mitochondrial membrane potential, triggering substantial apoptosis. Furthermore, a concurrent significant upregulation of apoptotic p53 and mitochondrial ND3 genes was observed, coupled with a notable decrease in the anti-apoptotic Bcl2 gene expression.Overall, Y2O3NPs demonstrate considerable promise as a therapeutic agent for skin epidermoid cancer due to their ability to selectively target and induce cytotoxic effects in A-431 cancer cells, all while causing minimal harm to normal HSF cells. This selective cytotoxicity appears to be associated with Y2O3NPs' ability to induce excessive ROS production and subsequent oxidative stress, leading to significant genomic DNA fragmentation, loss of mitochondrial permeability, and alterations in apoptotic and mitochondrial genes' expression, ultimately promoting apoptosis in A-431 cancer cells. These findings establish a foundation for further research into the utilization of Y2O3NPs in targeted cancer therapies and underscore the necessity for ongoing investigation into their safety and efficacy in clinical applications.

Burn wounds remain a significant global health concern, frequently exacerbated by bacterial infections that hinder healing and raise morbidity rates. Cefdinir, a third-generation cephalosporin antibiotic, is used to treat various conditions, but it has limitations such as low water solubility, limited bioavailability, and a short biological half-life. This study aimed to fabricate and optimize novel surfactant-based Cefdinir-loaded chitosan nanoparticles (CFD-CSNPs) for enhancing topical CFD delivery and efficacy in burn healing. Box-Behnken Design (BBD) was employed to develop optimized CFD-CSNPs using Design Expert® software, where the independent factors were chitosan concentration, chitosan: sodium tripolyphosphate ratio, pH, and surfactant type. Particle size PS, zeta potential ZP, Polydispersity index PDI, and entrapment efficiency EE% were evaluated as dependent factors. CFD-CSNPs were produced using the ionic gelation method. The optimized formula was determined and then examined for further in vitro and in vivo assessments. The optimized CFD-CSNPs exhibited acceptable PS, PDI, and ZP values. The EE% of CFD from CSNPs reached 57.89 % ± 1.66. TEM analysis revealed spherical morphology. In vitro release studies demonstrated a biphasic release profile up to (75.5 % ± 3.8) over 48 hrs. The optimized CFD-CSNPs showed improved antimicrobial efficacy against the tested microorganisms, exhibiting superior performance for both biofilm prevention and eradication. Enhanced wound healing activity was achieved by the optimized CFD-CSNPs in both in vitro and in vivo studies as confirmed by scratch wound assay and skin burn mice model. The current study advocates the efficacy of the innovative topical application of CFD-CSNPs for wound healing purposes and treatment of wound infections.

Cardiovascular disease is the leading cause of death worldwide, and it's of great importance to understand its underlying mechanisms and find new treatments. Sphingosine 1-phosphate (S1P) is an active lipid that exerts its effects through S1P receptors on the cell surface or intracellular signal, and regulates many cellular processes such as cell growth, cell proliferation, cell migration, cell survival, and so on. S1PR modulators are a class of modulators that can interact with S1PR subtypes to activate receptors or block their activity, exerting either agonist or functional antagonist effects. Many studies have shown that S1P plays a protective role in the cardiovascular system and regulates cardiac physiological functions mainly through interaction with cell surface S1P receptors (S1PRs). Therefore, S1PR modulators may play a therapeutic role in cardiovascular diseases. Here, we review five S1PRs and their functions and the progress of S1PR modulators. In addition, we focus on the effects of S1PR modulators on atherosclerosis, myocardial infarction, myocardial ischaemia/reperfusion injury, diabetic cardiovascular diseases, and myocarditis, which may provide valuable insights into potential therapeutic strategies for cardiovascular disease.

Novel series of nitric oxide-releasing thiazolidine-2,4-diones (NO-TZD-3a-d,5,6) and 3,4,5-trimethoxychalcone-based multifunctional 1,4-dihydropyrimidines (CDHPM-10a-g) have been designed and synthesised as potent broad-spectrum anticancer agents with potential VEGFR-2 inhibition. The designed analogs were evaluated for their anticancer activities towards a full panel of NCI-60 tumour cell lines and CDHPM-10a-g emerged mean %inhibitions ranging from 76.40 to 147.69%. Among them, CDHPM-10e and CDHPM-10f demonstrated the highest MGI% of 147.69 and 140.24%, respectively. Compounds CDHPM-10a,b,d-f showed higher mean %inhibitory activity than the reference drug sorafenib (MGI% = 105.46%). Superiorly, the hybrid CDHPM-10e displayed the highest potencies towards all the herein tested subpanels of nine types of cancer with MGI50 of 1.83 µM. Also, it revealed potent cytostatic single-digit micromolar activity towards the herein examined cancer cell lines. The designed compounds CDHPM-10a-g were exposed as potent non-selective broad-spectrum anticancer agents over all NCI subpanels with an SI range of 0.66-1.97. In addition, the target analog CDHPM-10e revealed potency towards VEGFR-2 kinase comparable to that of sorafenib with a sub-micromolar IC50 value of 0.11 µM. Also, CDHPM-10e could effectively induce Sub-G1-phase arrest and prompt apoptosis via caspase and p53-dependent mechanisms. Furthermore, CDHPM-10e revealed significant anti-metastatic activity as detected by wound healing assay. The modelling study implies that CDHPM-10e overlaid well with sorafenib and formed a strong H-bond in the DFG binding domain. The ADMET studies hinted out that CDHPM-10e met Pfizer's drug-likeness criteria. The presented novel potent anticancer agent merits further devotion as a new lead product in developing more chalcone-based VEGFR-2 inhibitors.

Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators of cancer pathogenesis, influencing various cellular processes and contributing to tumorigenesis. Sphingolipid metabolism has garnered interest as a potential target for cancer therapy owing to its considerable diagnostic and prognostic value. Recent studies have demonstrated that lncRNAs regulate tumor-associated metabolic reprogramming via sphingolipid metabolism. However, the precise nature of the interactions between lncRNAs and sphingolipid metabolism remains unclear. This review summarizes the key roles of lncRNAs and sphingolipid metabolism in tumorigenesis. We emphasize that the interaction between lncRNAs and sphingolipid metabolism influences their impact on both cancer prognosis and drug resistance. These findings suggest that lncRNA-sphingolipid metabolism interaction holds great potential as a newl target for cancer treatment.

Microbial prodigiosin pigment has been proposed as a promising biomolecule having an antibacterial, immunosuppressive, antimalarial, antineoplastic, and anticancer activities. The good outcome originates from getting natural pigment, which has many medical applications.

In this investigation, prodigiosin (PG) was extracted, characterized by UV-visible spectroscopy, thin-layer chromatography, mass spectroscopy, Fourier-transform infrared spectroscopy, and tested in various medical applications as an antibacterial, antioxidant, antibiofilm, anticancer, and wound healing agent at different concentrations. Antibacterial activity of PG pigment was shown against both Gram-positive and Gram-negative bacterial strains. Enterococcus faecalis was the most severely impacted, with minimum inhibitory value of 3.9 µg/mL. The formed biofilm by Pseudomonas aeruginosa was suppressed by 58-2.50% at prodigiosin doses ranging from 1000 to 31.25 µg/mL, respectively. The half-maximal inhibitory concentration (IC50) of 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) free radical was 74.18 ± 23.77 µg/mL. At 100 µg/mL concentration, OK482790 prodigiosin had no harmful effect on normal skin cells and exhibited mild wound healing properties. Additionally, molecular docking simulations confirmed the prodigiosin's interactions with target proteins, including epidermal growth factor receptor tyrosine kinase (EGFR-TK, PDB ID: 1M17), peptide deformylase from E. faecalis (PDB ID: 2OS1), acidic fibroblast growth factor (FGF-1, PDB ID: 3K1X), PA14_16140 protein from P. aeruginosa (PDB ID: 8Q8O), and human peroxiredoxin 5 (PDB ID: 1HD2) for explaining the anticancer, antibacterial, wound healing, antibiofilm, and antioxidant activities, respectively. Prodigiosin had favorable binding affinities and putative modes of action across various therapeutic domains.

This study pioneers the use of prodigiosin as a natural alternative to synthetic medicine since it fights germs, heals wounds, is antioxidant, and reduces biofilm formation.

Not applicable.

Two pure fungal strains were isolated and identified from Ficus sycomorus and Morus nigra, namely, Penicillium oxalicum (OR673586) and Phoma herbarum (OR673589), respectively. The extract and fractions of secondary metabolites of each fungus were evaluated for antioxidant, anti-inflammatory, antimicrobial, antibiofilm, antidiabetic, and cytotoxic activities. The chloroform fraction of P. oxalicum showed potent cytotoxic activity (IC50 = 7.695 μg mL-1) against Hep-G2 cell line, alongside moderate antioxidant and anti-inflammatory activities. On the other hand, the P. herbarum chloroform fraction showed potent antioxidant (DPPH IC50 = 5.649 μg mL-1) and antidiabetic activities (IC50 = 14.91 μg mL-1) against inhibition of α-glucosidase, in addition to moderate cytotoxicity, anti-inflammatory, and antimicrobial activities. Guided cytotoxic fractionation leads to identifying bioactive compounds using hyphenated techniques. LC-MS identified fourteen compounds for P. herbarum and thirteen compounds for P. oxalicum. Three known compounds, mevalolactone (1), glycerol monolinoleate (3), and ergosterol (7) in addition to one new compound, barcelonyl acetate (2), were isolated from P. herbarum. On the other hand, four known compounds, 4-hydroxyphenyl acetic acid (4), secalonic acid D (5), altersolanol A (6), and ergosterol (7), were isolated from P. oxalicum. Altersolanol A (6) and secalonic acid D (7) exhibited outstanding cytotoxic activity against Hep-G2 and Caco-2 cell lines, with IC50 values ranging from 0.00038 to 0.208 μM. In silico study findings showed altersolanol A (6), 4-hydroxyphenyl acetic acid (4), glycerol monolinoleate (3), and barcelonyl acetate (2) displayed significant potential but may benefit from further optimization as lead for developing potent c-Jun N-terminal kinase 2 (JNK2, PDB: 3NPC) inhibitors, potentially leading to novel therapeutic strategies targeting cancer therapy.

Vancomycin-resistant enterococci (VRE) represent a public health threat due to the few available treatments. Such alarm has triggered worldwide initiatives to develop effective antimicrobial compounds and novel delivery and therapeutic strategies. vanA operon is responsible for most cases of acquired vancomycin resistance in enterococci.

Development of a transcription factor decoy (TFD) system as a vanA gene transcription-inhibitor.

Vancomycin MIC was determined in the presence of TFD-lipoplexes. Additionally, the effect of TFD-lipoplexes on the expression level of the vanA gene and the growth pattern of E. faecalis was evaluated. The haemolytic activity of the developed TFD-lipoplexes and their cytotoxicity were examined. TFD-lipoplexes efficiency in treating vancomycin-resistant E. faecalis (VREF) infection was tested in vivo using a systemic mice infection model.

A reduction in vancomycin MIC against VRE from 256 mg/L (resistant) to 16 mg/L (intermediate susceptible), in the presence of TFD-lipoplexes, was recorded. The developed TFD-lipoplexes lacked any effect on E. faecalis growth and significantly reduced the transcription level of the vanA gene by about 3-fold. In an initial evaluation of the safety of TFD-lipoplexes, they were found not to be overtly haemolytic to human blood or cytotoxic to human skin fibroblast cells. The co-administration of TFD-lipoplexes and vancomycin efficiently eradicated VREF infection in vivo.

The developed TFD-lipoplexes successfully restored vancomycin activity against VREF. They offer a safe effective unconventional therapy against this stubborn organism and present a revolution in gene therapy that can be applied to other resistance-encoding genes in various organisms.

The rising demand for innovative antimicrobial solutions has shifted focus towards silver nanoparticles (AgNPs), especially those produced through eco-friendly methods. This study introduces a novel approach utilizing actinomycetes strains-Streptomyces albus, Micromonospora maris, and Arthrobacter crystallopoietes-to biosynthesize AgNPs with remarkable antibacterial properties. Through molecular characterization, we identified unique features of these nanoparticles, and computational modeling suggested significant ion-ligand interactions with proteins 6REV and 3K07. Our research highlights the promise of these biogenically synthesized nanoparticles in advancing biomedical applications. Actinomycetes were sourced and screened for their ability to produce metallic nanoparticles, revealing that among 35 samples, only six showed this capability. Notably, Streptomyces albus strain smmdk14 (OR685674), Micromonospora maris strain smmdk13 (OR685672), and Arthrobacter crystallopoietes strain smmdk12 (OR685674) were identified as effective silver nanoparticle producers. The synthesized nanoparticles demonstrated potent antibacterial activity against common pathogens including E. coli, Pseudomonas aeruginosa, Klebsiella spp., Enterococcus faecalis, Staphylococcus aureus, and Acinetobacter spp. The data obtained from color change observation, UV-visible spectrophotometry, Zeta potential, FTIR spectroscopy, and transmission electron microscopy (TEM) characterized AgNPs potentiality. The nanoparticles were spherical, with sizes ranging from 6.46 nm to 24.7 nm. Optimization of production conditions, comparison of antimicrobial effects with antibiotics, evaluation of potential toxicity, and assessment of wound-healing capabilities were also conducted. The biosynthesized AgNPs exhibited superior antibacterial properties compared to traditional antibiotics and significantly accelerated wound healing by approximately 66.4 % in fibroblast cell cultures. Additionally, computational analysis predicted interactions between various metal ions and specific amino acid residues in proteins 6REV and 3K07. Overall, this study demonstrates the successful creation of AgNPs with notable antibacterial and wound-healing properties, underscoring their potential for medical applications.

In the current study, a new series of benzenesulfonamides 6a-r was designed and synthesized as dual VEGFR-2 and FGFR1 kinase inhibitors with anti-cancer activity. The 4-trifluoromethyl benzenesulfonamide 6l exhibited the highest dual VEGFR-2/FGFR1 inhibitory activity with IC50 values of 0.025 and 0.026 µM, respectively. It showed a higher activity than sorafenib and staurosporine by 1.8- and 1.3-fold, respectively. Furthermore, compound 6l was further tested on EGFR and PDGFR-β kinases showing IC50 values of 0.106 and 0.077 µM, respectively. The target compounds were tested for their anticancer activity against NCI-60 panel of cancer cell lines at 10 µM concentration, where compound 6l displayed the highest mean growth inhibition percent % (GI%) of 60.38%. Compounds 6a, 6b, 6e, 6f, 6h-l, and 6n-r revealed promising GI% on breast cancer cell lines (MCF-7, T-47D, and MDA-MB-231), and were subjected to IC50 determination on these cell lines. The tested compounds showed a higher activity on T-47D and MCF-7 cell lines over MDA-MB-231 cell line compared to the used reference standard; sorafenib. Compounds 6e, 6h-j, 6l and 6o revealed IC50 values ≤ 20 µM against T-47D cell line, furthermore, they were found to be non-cytotoxic on Vero normal cell line. Furthermore, the effect of the most active compounds 6i, and 6l in T-47D cells on cell cycle analysis progression, cell apoptosis, and apoptosis markers was investigated. Both compounds arrested cell cycle progression at G1 phase, furthermore, they enhanced early and late apoptosis, as well as necrosis. The capability of compounds 6i, and 6l to induce apoptosis was further confirmed by their ability to raise BAX/BCl-2 ratio and caspase-3 level in the treated cells. Cell migration assay revealed that both compounds 6i and 6l have anti-migratory effects compared to control T-47D cells after 24, and 48 h. Molecular docking studies for compounds 6a-r on VEGFR-2 and FGFR1 binding sites showed that they exhibit an analogous binding mode in both target kinases which agrees with that of type II kinase inhibitors.

Phyto-nanotechnology offers a sustainable method for synthesizing biocompatible metal nanoparticles (NPs) with therapeutic potential. The diverse medicinal flora in the UAE, particularly Leptadenia pyrotechnica (LP), provides a vital resource for advancing this research area. This plant is historically valued in the region for its wide medicinal applications due to its abundance of bioactive compounds.

In this study, eco-friendly, straightforward, and low-temperature hydrothermal synthesis methods were applied to synthesize potentially therapeutic Zn and Fe NPs using LP extracts. The generated NPs were characterized using UV-VIS, FT-IR, SEM, EDX, XRD and DLS. Moreover, they were investigated for their total phenolic and flavonoid contents, along with their antioxidant and skin anticancer effects.

The UV-Vis spectra disclosed absorption band at about 275 nm, and the FT-IR confirmed the successful coating of the NPs with the plants' phytochemicals, thus ensuring the successful bio-fabrication of the proposed NPs. SEM/EDX outcomes suggest a more potent reducing effect of the aqueous extract, while a more effective coating of the alcoholic extract. DLS revealed monodispersed NPs, with average sizes ranging from 43.82 to 207.8 nm. LFeC demonstrated the highest phenolic and flavonoid contents (49.96±4.76 μg of GAE/mg of DW and 43.89±2.89 μg of Qu/mg of DW, respectively) and the greatest potency against skin cancer cell lines (IC50=263.56 µg/mL). However, LZnC exhibited the strongest radical scavenging effect against DPPH and ABTS radicals (IC50=139.45µg/mL and 35.1µg/mL, respectively).

The results of this study demonstrated that both extracts of LP are effective in the green synthesis of Fe and Zn nanoparticles for biomedical applications, with alcoholic extracts providing superior coating, capping, and stabilizing properties, leading to lower agglomeration, higher carbon content, total phenolic and flavonoid contents, along with enhanced anticancer and antioxidant effects. This work gives a showcase of sustainable materials that are promising for therapeutic applications.

Due to the adverse effects of industrial chemicals and their carcinogenicity and toxicity for humans, the debates have increased on using natural preservatives. This study was conducted to investigate the inhibitory effect of pure nisin and nisin nanoparticles (nisin NPs) against Aspergillus flavus in vivo by inoculation in laboratory-manufactured Ras cheese. A novel, safe, and natural approach of nanoprecipitation using acetic acid was employed to prepare nisin nanoparticles. The prepared NPs were characterized using zeta-sizer, FTIR, and transmission electron microscopy (TEM). Furthermore, the cytotoxicity of nisin NPs on Vero cells was assessed. The minimum inhibitory concentrations (MICs) of nisin and its nanoparticles were determined in vitro against A. flavus isolates using the agar well-diffusion method. The sensory evaluation of manufactured Ras cheese was conducted over a 60-day storage period.

The obtained results showed a strong antifungal activity of nisin NPs (0.0625 mg/mL) against A. flavus strain in comparison with pure nisin (0.5 mg/mL). Notably, the count decreased gradually by time from 2 × 108 at zero time and could not be detected at the 7th week. The count with pure nisin decreased from 2 × 108 at zero time and could not be detected at the 10th week where it's enough time to produce aflatoxins in cheese. The MICs of nisin and nisin NPs were 0.25 and 0.0313 mg/mL, respectively. Nisin NPs used in our experiment had good biocompatibility and safety for food preservation. Additionally, the sensory parameters of the manufactured Ras cheese inoculated with nisin and nisin NPs were of high overall acceptability (OAA).

Overall, the results of this study suggested that adding more concentration (˃0.0625 mg/mL) from nisin nanoparticles during the production of Ras cheese may be a helpful strategy for food preservation against A. flavus in the dairy industry.

Pancreatic cancer is known to be the most lethal cancer. Fewer new treatments are being developed for pancreatic cancer as compared to other cancers. The bioactive lipid S1P, which is mainly regulated by sphingosine kinase 1 (SK1) and sphingosine kinase 2 (SK2) enzymes, plays significant roles in pancreatic cancer initiation and exacerbation. S1P controls many signaling pathways to modulate the progression of pancreatic cancer through the G-coupled receptor S1PR1-5. Several papers reporting amelioration of pancreatic cancer via modulation of S1P levels or downstream signaling pathways have previously been published. In this paper, for the first time, we have reviewed the results of previous studies to understand how S1P and its receptors contribute to the development of pancreatic cancer, and whether S1P can be a therapeutic target. In addition, we have also reviewed papers dealing with the effects of SK1 and SK2, which are kinases that regulate the level of S1P, on the pathogenesis of pancreatic cancer. We have also listed available drugs that particularly focus on S1P, S1PRs, SK1, and SK2 for the treatment of pancreatic cancer. Through this review, we would like to suggest that the SK/S1P/S1PR signaling system can be an important target for treating pancreatic cancer, where a new treatment target is desperately warranted.

The UAE harbors a rich diversity of wild medicinal plants, such as Calotropis procera (CP), that are renowned for their extensive use in traditional medicine due to their abundance of bioactive phytochemicals. Zinc and iron metals possess significant pharmacological effects including antioxidant and anticancer properties. In this study, nanoparticles (NPs) containing zinc and iron were green synthesized utilizing ethanolic and aqueous extracts of CP aerial parts. UV-Vis spectra revealed absorption peaks around 270-275 nm, while FT-IR analysis confirmed successful coating of the NPs with plant's phytochemicals. SEM/EDX analysis indicated a more potent reducing effect of the aqueous extract, whereas the alcoholic extract demonstrated more effective coating of the NPs. DLS showed monodispersed NPs with average sizes of 32.67-202 nm. The alcoholic extract-based zinc and iron NPs exhibited the highest phenolic and flavonoid contents (51.06 ± 2.82 µg of GAE/mg of DW and 66.26 ± 1.12 µg of Qu/mg of DW, respectively) and the strongest antioxidant effect against ABTS and DPPH radicals (IC50 = 52.81 and 148.46 µg/mL, respectively). The aqueous extract-based zinc NPs demonstrated the greatest cytotoxicity against A-431 cell lines (IC50 = 188.97 µg/mL). The findings highlight promising potential of these sustainable materials for therapeutic applications, indicating a need for continued research and development in this area.

Colorectal cancer (CRC) is a prevalent cancer with high morbidity and mortality rates worldwide. Late diagnosis is a significant contributor to low survival rates in a minority of cases. The study aimed to perform a robust pipeline using integrated bioinformatics tools that will enable us to identify potential diagnostic and prognostic biomarkers for early detection of CRC by exploring differentially expressed genes (DEGs). In addition to, testing the capability of replacing chemotherapy with plant extract in CRC treatment by validating it using real-time PCR. RNA-seq data from cancerous and adjacent normal tissues were pre-processed and analyzed using various tools such as FastQC, Kallisto, DESeq@ R package, g:Profiler, GNEMANIA-CytoScape and CytoHubba, resulting in the identification of 1641 DEGs enriched in various signaling routes. MMP7, TCF21, and VEGFD were found to be promising diagnostic biomarkers for CRC. An in vitro experiment was conducted to examine the potential anticancer properties of 5-fluorouracile, Withania somnifera extract, and their combination. The extract was found to exhibit a positive trend in gene expression and potential therapeutic value by targeting the three genes; however, further trials are required to regulate the methylation promoter. Molecular docking tests supported the findings by revealing a stable ligand-receptor complex. In conclusion, the study's analysis workflow is precise and robust in identifying DEGs in CRC that may serve as biomarkers for diagnosis and treatment. Additionally, the identified DEGs can be used in future research with larger sample sizes to analyze CRC survival.

Enterococcus faecalis is a troublesome nosocomial pathogen that acquired resistance to most available antimicrobial agents. Antivirulence agents represent an unconventional treatment approach. Here, transcription factor decoy (TFD)-loaded cationic liposomes (TLL) were developed as an inhibitor of the Fsr quorum-sensing system and its associated virulence traits, in E. faecalis. The consensus sequence of the FsrA binding site was found conserved among 651 E. faecalis annotated genomes. The TFD was synthesized as an 82 bp DNA duplex, containing the conserved binding sequence, and loaded onto cationic liposomes. The optimum loading capacity, mean particle size, and zeta potential of the TLL were characterized. The developed TLL lacked any effect on E. faecalis growth and significantly inhibited the in vitro production of the proteolytic enzymes controlled by the Fsr system; gelatinase and serine protease, in a concentration-dependent manner. This inhibition was accompanied by a significant reduction in the transcription levels of FsrA-regulated genes (fsrB, gelE, and sprE). The developed TLL were safe as evidenced by the nonhemolytic effect on human RBCs and the negligible cytotoxicity on human skin fibroblast cells. Moreover, in the larvae infection model, TLL displayed a significant abolish in the mortality rates of Galleria mellonella larvae infected with E. faecalis. In conclusion, the developed TLL offer a new safe strategy for combating E. faecalis infection through the inhibition of quorum-sensing-mediated virulence; providing a platform for the development of similar agents to combat many other pathogens.

Breast cancer is among the most prevalent tumors worldwide. In this study, in-situ forming implants (ISFIs) containing rosuvastatin calcium were prepared using three types of poly (D, L-lactic-co-glycolic acid) (PLGA), namely, PLGA 50/50 with ester terminal and PLGA 75/25 with ester or acid terminal. Additionally, polydimethylsiloxane (PDMS) was added in concentrations of 0, 10, 20, and 30% w/v to accelerate matrix formation. The prepared ISFIs were characterized for their rheological behaviors, rate of matrix formation, and in-vitro drug release. All the prepared formulations revealed a Newtonian flow with a matrix formation rate between 0.017 and 0.059 mm/min. Generally, increasing the concentration of PDMS increased the matrix formation rate. The prepared implants' release efficiency values ranged between 46.39 and 89.75%. The ISFI containing PLGA 50/50 with 30% PDMS was selected for further testing, as it has the highest matrix formation rate and a promising release efficiency value. Copper-selenium nanoparticles were prepared with two different particle sizes (560 and 383 nm for CS1 and CS2, respectively) and loaded into the selected formulation to enhance its anticancer activity. The unloaded and loaded implants with rosuvastatin and copper-selenium nanoparticles were evaluated for their antibacterial activity, against Gram-positive and negative microorganisms, and anticancer efficacy, against MCF-7 and MDA-MB-231 cell lines. The results confirmed the potency of rosuvastatin calcium against cancer cells and the synergistic effect when loaded with smaller particle sizes of copper-selenium nanoparticles. This formulation holds a considerable potential for efficient breast cancer therapy.

Due to vincristine sulfate's (VCR sulfate) toxicity and non-specific targeting, which might adversely damage healthy cells, its clinical application is restricted. In this study, we loaded VCR sulfate on exosomes generated from mesenchymal stem cells (MSCs) to enhance its targeted distribution. Exosomes are able to deliver molecules to specific cells and tissues and have therapeutic potential. In this study, we isolated exosomes from MSCs, and using probe-sonication approach loaded them with VCR sulfate. Using SRB assay, the cytotoxicity of VCR sulfate-Exo was assessed in T47D breast cancer cells, and the results were contrasted with those of free VCR sulfate. Then We labeled markers (CD44+/CD24-) in the cell line to assess the targeting effectiveness of VCR sulfate-Exo using flow cytometry. Our results showed that the cytotoxicity of VCR sulfate-Exo was nearly the same as that of VCR sulfate. Flow cytometry analysis revealed that VRC sulfate-Exo was more effectively targeted to MSCs than free VCR sulfate. Our study shows that loading VCR sulfate to MSCs-derived exosomes can improve their targeted delivery and lessen their side effects. Additional research is required to determine VCR sulfate-Exo's in vivo effectiveness and safety and improve the loading and delivery strategies.

New 3-substituted oxindole derivatives were designed and synthesized as antiproliferative agents. The antiproliferative activity of compounds 6a-j was evaluated against 60 NCI cell lines. Among these tested compounds, compounds 6f and 6g showed remarkable antiproliferative activity, specifically against leukemia and breast cancer cell lines. Compound 6f was the most promising antiproliferative agent against MCF-7 (human breast cancer) with an IC50 value of 14.77 µM compared to 5-fluorouracil (5FU) (IC50 = 2.02 µM). Notably, compound 6f hampered receptor tyrosine EGFR fundamentally with an IC50 value of 1.38 µM, compared to the reference sunitinib with an IC50 value of 0.08 µM. Moreover, compound 6f afforded anti-tubulin polymerization activity with an IC50 value of 7.99 µM as an outstanding observable activity compared with the reference combretastatin A4 with an IC50 value of 2.64 µM. In silico molecular-docking results of compound 6f in the ATP-binding site of EGFR agreed with the in vitro results. Besides, the investigation of the physicochemical properties of compound 6f via the egg-boiled method clarified good lipophilicity, GIT absorption, and blood-brain barrier penetration properties.

The present study evaluated, in laboratory and field, the efficacy and safety of formulations of Pelargonium graveolens (geranium - G), Origanum majorana (oregano - O) commercial essential oils (EO) and thymol (T) to control of Rhipicephalus sanguineus sensu lato. In the laboratory, three formulas (A: 2% tween 80%, B: powder and C: nanoemulsion) by a mixture of these components (GOT) were prepared and evaluated, and the best one was used to assess its safety and field application against R. sanguineus s. l. on naturally infested dogs. Besides the major compounds of the EO used were identified. The results of the lab study showed that formula A (2.5 g of each G + O + T + 2% tween 80 to complete 100 mL) was significantly more effective than the other two formulas tested and exhibited highly effective adulticidal, larvicidal, and ovicidal activity against R. sanguineus s.l. Significant LC50 and LC90 values of GOT were evaluated (13.4 and 21.5 mg/mL, respectively) for the adulticidal activity, (2.81 and 4.46 mg/mL, respectively) for ovicidal activity and (2.44 and 4.45 mg/mL, respectively) for larvicidal activity. The safety of formula A has been proven by the absence of its cytotoxicity on a cell line of human epidermoid carcinoma. Citronella and carvacrol were the major compounds identified in the commercial essential oils of P. graveolens and O. majorana, respectively. Formula A was used in a field control trial for almost 8 months, during the tick infestation season (April to November, 2022). Fourteen naturally infested dogs were divided into two groups, each with seven dogs. One group received formula A spraying five times during an experiment that continued for 8 months, while the other group received treatment with commercially available malathion acaricide. The animals were sprayed on five occasions throughout the experiment (April, June, July, August, and September). The results showed a substantial percentage of effectiveness after the first application of formula A with a 99.3% reduction in tick count at day 28 post-application (PA). In the case of severe infestation 60 days after the first application of formula A (more than 180 ticks per dog), the second application was done, achieving an efficacy of 54.9% at day 3 PA, so an emergency spray was done at day 5 PA to combat the rest of the tick infestation, achieving efficacy of 99% after 3 days. Consequently, a regular spray (third, fourth, and fifth application) was done every 35 days. This regular spray revealed 100% effectiveness at 14 days PA. Biochemical parameters of treated dogs were evaluated to confirm the safety of formula A. Creatinine, ALT, and albumin of the dogs treated with formula A were within the normal range of dogs, while urea and AST were higher than the normal range. In conclusion, formula A can safely treat R. sanguineus s.l. infestations in dogs with regular application every 5 weeks.

The nature of nano molecules as a self-assembled nanocomposite surface depends on the nanoparticles of sodium butyrate, cellulose, and pycnogenol; the synthesis is achieved via precipitation and grinding methods. The excellent functionalized surface of nanocomposite (NCP) enables the loading of the selected drugs, where the efficiency of the NCP surface arrived at 92.2 %. The electrochemical behavior emphasized the success of a functionalized NCP surface for incorporation with drugs for the drug delivery system, the results of cytotoxicity detect the effect of NCP on the mouse normal liver (BNL) cells, where the high and low concentrations on the BNL cells have a safe dose. Cell viability with BNL cells was reported at 101.8 % with10 μL and 100.12 % with 100 μL, the interaction between the NCP and the human serum albumin (HSA) at room temperature. The low interaction rate with the glutamate and increased binding with the oxidized glutathione disulfide (GSSG) and reduced glutathione (SGH) reflect the antioxidant activity of NCP. The strong binding of NCP with biomolecules such as glucose is referred to as the biosensor property. The results recommend that NCP is an excellent nanocarrier for drug delivery and glucose biosensors for diabetes.

In this study, flower and leaf extracts of Colvillea racemosa were considered a source of bioactive compounds. In this context, the objective of the study focused on investigating the anticancer potential as well as the phytochemical composition of both extracts. The extracts were analyzed by UPLC-ESI-QTOF-MS, and the bioactivity was tested using in vitro antioxidant assays (FRAP, DPPH, and ABTS) in addition to cytotoxic assays on non-small cell lung cancer cell line (A549). Our results clearly indicated the potent radical scavenging capacity of both extracts. Importantly, the flower extract exhibited a greater antioxidant capacity than the leaf extract. In terms of cytotoxic activity, leaf and flower extracts significantly inhibited cell viability with IC50 values of 17.0 and 17.2 µg/mL, respectively. The phytochemical characterization enabled the putative annotation of 42 metabolites, such as saccharides, phenolic acids, flavonoids, amino acids, and fatty acids. Among them, the flavonoid C-glycosides stand out due to their high relative abundance and previous reports on their anticancer bioactivity. For a better understanding of the bioactive mechanisms, four flavonoids (vitexin, kaempferol-3-O-rutinoside, luteolin, and isoorientin) were selected for molecular docking on hallmark protein targets in lung cancer as represented by γ-PI3K, EGFR, and CDK2 through in-silico studies. In these models, kaempferol-3-O-rutinoside and vitexin had the highest binding scores on γ-PI3K and CDK2, followed by isoorientin, so they could be highly responsible for the bioactive properties of C. racemosa extracts.

The ability of wound dressing materials to tackle skin pathogens colonization that is associated with open wound infections is limited. Recently, green-synthesized metal oxide nanoparticles has received a lot of attention to overcome this limitation. However, titanium dioxide nanoparticles (TiO2-NPs) exhibit exceptional antibacterial properties. In this work, several concentrations (0, 1, 3, and 5 wt.%) of TiO2 NPs prepared using Aloe vera leaf extract were added to a blend of polyvinyl alcohol and sodium alginate (PVA:SA). This nanocomposite was designed to enhance the healing process of wounds. The interaction between the PVA:SA composite and the TiO2 NPs was confirmed by FTIR. The thermal behavior of the nanocomposite films was investigated using DSC and TGA. The experimental results indicate that the glass transition temperatures of the nanocomposites increased by increasing the added amount of TiO2 NPs to be 53.7 °C (1 wt.%), 55.8 °C (3 wt.%), and 60.6 °C (5 wt.%), which were consistently lower than the glass transition temperature of the matrix material (69.6 °C). The Dynamic Mechanical Analysis was examined. The nanocomposite doped with 5 wt.% of TiO2 NPs detected a high storage modulus (21.6 × 108). Based on swelling and degradation studies, the prepared PVA:SA:TiO2 nanocomposite films have an excellent swelling rate, and the inclusion of TiO2 NPs increases the stability of the polymeric matrix. The PVA:SA:TiO2 nanocomposite films exhibited a superior antibacterial efficacy against Gram-positive bacteria such as Bacillus cereus and Staphylococcus aureus, compared to their effectiveness against Gram-negative bacteria like Escherichia coli. Moreover, the nanocomposite films were biocompatible with Human Skin Fibroblast. Therefore, the developed PVA:SA:TiO2 nanocomposite films suit wound dressing applications.

Urgent requirements for medication from chronic inflammation and cancer are considerably interested, while, the recent reports were considered with investigating simple methods for synthesis. Metal-modified carbon quantum dots ("M-CQDs") were successfully ingrained from carboxymethyl cellulose under the assistance of infra-red irradiation. The current approach demonstrates a study for the effect of structural tuning for biomedical performance of CQDs via modifying of CQDs with either gold (Au-CQDs) or platinum (Pt-CQDs). Successive nucleation of Au-CQDs and Pt-CQDs was confirmed via different instrumental analyses like, TEM micrographs, Zeta potential, XRD, FTIR, 1HNMR& 13CNMR spectra. The data reveal that, modification of CQDs (8.7 nm) with gold was reflected in insignificant effect on the mean size of CQDs (8.9 nm), whereas, doping of platinum resulted in slight enlargement of the size (12.4 nm). However, Pt-CQDs were exhibited with the highest anti-inflammatory (cell viability percent 78 %) and antimicrobial action. On the other hand, Au-CQDs were shown with the highest anticancer affinity (reduction of cell viability 83 %) compared to the others. The current study approved the superiority of CQDs modified with either gold or platinum to be successfully applicable as potential therapeutic reagents for the treatment of either cancer or inflammation diseases.