Search

In this article, ZnO:NiO:CuO nanocomposites (NCPs) were synthesized using a hydrothermal method, with different Zn : Ni : Cu molar ratios (1 : 1 : 1, 2 : 1 : 1, 1 : 2 : 1, and 1 : 1 : 1). The PXRD confirmed the formation of a NCP consisting of ZnO (hexagonal), NiO (cubic), and CuO (monoclinic) structures. The crystallite sizes of NCPs were calculated using Debye Scherrer and Williamson-Hall methods. The calculated crystalline sizes (Scherrer method) of the NCPs were determined to be 21, 27, 23, and 20 nm for the molar ratios 1 : 1 : 1, 2 : 1 : 1, 1 : 2 : 1, and 1 : 1 : 2, respectively. FTIR spectra confirmed the successful formation of heterojunction NCPs via the presence of metal-oxygen bonds. The UV-vis spectroscopy was used to calculate the bandgap of synthesized samples and was found in the range of 2.99-2.17 eV. SEM images showed the mixed morphology of NCPs i.e. , irregular spherical and rod-like structures. The dielectric properties, including AC conductivity, dielectric constant, impedance, and dielectric loss parameters were measured using an LCR meter. The DC electrical measurements revealed that NCPs have a high electrical conductivity. All the NCPs were evaluated for the photocatalytic degradation of Methylene blue (MB), methyl orange (MO), and a mixture of both of these dyes. The NCPs with a molar ratio 1 : 1 : 2 (Zn : Ni : Cu) displayed outstanding photocatalytic activity under sunlight, achieving the degradation efficiency of 98% for methylene blue (MB), 92% for methyl orange (MO) and more than 87% in the case of a mixture of dyes within just 90 minutes of illumination. The antibacterial activity results showed the more noxious nature of NCPs against Gram-negative bacteria with a maximum zone of inhibition revealed by the NCPs of molar ratio 1 : 2 : 1 (Zn : Ni : Cu). On the basis of these observations, it can be anticipated that the NCPs can be successfully employed for the purification of contaminated water by the degradation of hazardous organic compounds and in antibacterial ointments., Competing Interests: The authors have no relevant financial or non-financial interests to disclose., (This journal is © The Royal Society of Chemistry.)

Biopolymer microgels present many opportunities in biomedicine and tissue engineering. To understand their in vivo behavior in therapeutic interventions, long-term monitoring is critical, which is usually achieved by incorporating fluorescent materials within the hydrogel matrix. Current research is limited due to issues concerning the biocompatibility and instability of the conventional fluorescent species, which also tend to adversely affect the bio-functionality of the hydrogels. Here, we introduce a microfluidic-based approach to generate nitrogen-functionalized graphene quantum dot (NGQD) incorporated gelatin methacryloyl (GelMA) hydrogel microspheres, capable of long-term monitoring while preserving or enhancing the other favorable features of 3D cell encapsulation. A multilayer droplet-based microfluidic device was designed and fabricated to make monodisperse NGQD-loaded GelMA hydrogel microspheres encapsulating skeletal muscle cells (C2C12). Control over the sizes of microspheres could be achieved by tuning the flow rates in the microfluidic device. Skeletal muscle cells encapsulated in these microgels exhibited high cell viability from day 1 (82.9 ± 6.50%) to day 10 (92.1 ± 3.90%). The NGQD-loaded GelMA microgels encapsulating the cells demonstrated higher metabolic activity compared to the GelMA microgels. Presence of sarcomeric α-actin was verified by immunofluorescence staining on day 10. A fluorescence signal was observed from the NGQD-loaded microgels during the entire period of the study. The investigation reveals the advantages of integrating NGQDs in microgels for non-invasive imaging and monitoring of cell-laden microspheres and presents new opportunities for future therapeutic applications.

Seawater intrusion is a growing concern for coastal regions in Bangladesh. Overexploitation of groundwater, low rainfall, a high rate of evaporation, rising sea level, cyclones, storm surges, and shrimp cultivation are the causes of seawater intrusion that polluted the groundwater near the coastal area. High values of EC, TDS, Na + , and Cl - ions in groundwater indicate the seawater intrusion. Piper's Trilinear and Durov diagrams of groundwater indicated that most gathered groundwater show predominantly Na-Cl-type of water. Based on the USSL diagram, it is observed that the salinity of the study area is medium to high and the alkalinity is medium to very high. Also, in view of the Wilcox outline, most of the samples in the area of interest are permissible to doubtful, and doubtful to unsuitable. Chloride is moderately correlated with Na + (R 2  = 0.590) and poorly correlated with (HCO 3 -  + CO 3 2- ) (R 2  = 0.128), which indicates seawater intrusion. According to a comparison of the levels of Fe and Mn in the groundwater of the study area with those recommended by the World Health Organization (WHO) and Department of the Environment (DOE), twenty-two out of thirty-one samples exceed the acceptable limit for Fe and thirty out of thirty-one samples fall within the acceptable limit for Mn. The calculated water quality index reveals that most samples are of low drinking water quality. The research area's poor water type is found in the north-central and southern parts. The WQI geographic variation map reveals that the study's water has a WQI of more than 100, making it unsuitable for consumption. The final seawater intrusion vulnerability map clearly identifies the moderate to highly vulnerable zone of the study area using DRASTIC index parameters. DRASTIC index parameters revealed that some portions of the northwestern part of the sample area show a moderately vulnerable zone. And the rest of the sampling area indicates the highly vulnerable zone., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Dilute magnetic semiconductor Zn 1-x Cu x O (x = 0, 1.5, 3.0, and 4.5%) nanorods were prepared by hydrothermal method. The impact of dopant concentration on the physical properties was investigated along with the anti-bacterial and photocatalytic activities. Synthesis of ZnO nanorods was confirmed by the characteristic band at 380 nm in UV-Visible spectra of the synthesized samples. A red shift in absorbance spectra was observed from 380 to 465 nm with an increase in dopant concentration. The hexagonal wurtzite geometry and rod-like morphology of Cu-doped ZnO nanorods having an average size of 29 nm were confirmed by X-ray diffraction analysis (XRD) and scanning electron microscopy (SEM), respectively. An increase in the crystallinity of the material was observed with an increase in the dopant (Cu) ratio without any alteration in geometry. EDX analysis was used to confirm the purity of samples. FTIR spectra were recorded to explore the functional group present in samples. The hysteresis loop drawn by a vibrating-sample magnetometer (VSM) was utilized to analyze the ferromagnetic behavior. As-synthesized pure and Cu-ZnO nanorods were evaluated for their photocatalytic behavior for the photodegradation of methyl orange (MO) dye. Zn 1 - x Cu x O with x = 4.5%, pH 3, and catalyst dosage of 0.5 g has shown the maximum efficiency. Results elucidated > 81% degradation of MO dye with a rate constant (k) value of - 1.930 × 10 -2  min -1 in just 90 min of exposure to a visible light source. ZnO nanorods have also exhibited anti-bacterial potential against gram-positive and gram-negative strains of bacteria. However, smaller size nanorods were found more effective to suppress the growth of gram-negative bacteria. A slight decrease (11%) in catalytic potential was observed in the 5th cycle during recycling and reuse experiments., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Phosphorus (P), an essential macronutrient, plays a pivotal role in the growth and development of plants. However, the limited availability of phosphorus in soil presents significant challenges for crop productivity, especially when plants are subjected to abiotic stresses such as drought, salinity and extreme temperatures. Unraveling the intricate mechanisms through which phosphorus participates in the physiological responses of plants to abiotic stresses is essential to ensure the sustainability of agricultural production systems. This review aims to analyze the influence of phosphorus supply on various aspects of plant growth and plant development under hostile environmental conditions, with a special emphasis on stomatal development and operation. Furthermore, we discuss recently discovered genes associated with P-dependent stress regulation and evaluate the feasibility of implementing P-based agricultural practices to mitigate the adverse effects of abiotic stress. Our objective is to provide molecular and physiological insights into the role of P in regulating plants' tolerance to abiotic stresses, underscoring the significance of efficient P use strategies for agricultural sustainability. The potential benefits and limitations of P-based strategies and future research directions are also discussed.

Metastatic castration-resistant prostate cancer (mCRPC) cells can de novo biosynthesize their own cholesterol and overexpress proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 proved to contribute to mCRPC cell motility since PCSK9 knockdown (KD) in mCRPC CWR-R1ca cells led to notable reductions in cell migration and colony formation. Human tissue microarray results proved a higher immunohistoscore in patients ≥ 65 years old, and PCSK9 proved to be expressed higher at an early Gleason score of ≤7. The fermentation product pseurotin A (PS) suppressed PCSK9 expression, protein-protein interactions with LDLR, and breast and prostate cancer recurrences. PS suppressed migration and colony formation of the CWR-R1ca cells. The progression and metastasis of the CWR-R1ca-Luc cells subcutaneously (sc) xenografted into male nude mice fed a high-fat diet (HFD, 11% fat content) showed nearly 2-fold tumor volume, metastasis, serum cholesterol, low-density lipoprotein cholesterol (LDL-C), prostate-specific antigen (PSA), and PCSK9 levels versus mice fed a regular chow diet. Daily oral PS 10 mg/kg treatments prevented the locoregional and distant tumor recurrence of CWR-R1ca-Luc engrafted into nude mice after primary tumor surgical excision. PS-treated mice showed a significant reduction in serum cholesterol, LDL-C, PCSK9, and PSA levels. These results comprehensively validate PS as an mCRPC recurrence-suppressive lead by modulating the PCSK9-LDLR axis.

Herein, a one-pot synthesis of tetra-substituted imidazole, 4-chloro-2-(1-(4-methoxyphenyl)-4,5-diphenyl-1 H -imidazol-2-yl)phenol (HL), is reported by the reaction of benzil, 5-bromosalicylaldehyde, ammonium acetate and anisidine. The synthesized imidazole was reacted with salts of 1 st row transition metals (Co(ii), Ni(ii), Cu(ii), Mn(ii) and Zn(ii)) to obtain metal complexes. The structure of the compounds was confirmed using various spectroscopic and analytical techniques. HL, which is crystalline, was characterized by SC-XRD. Subsequently, the synthesized compounds were evaluated for their antioxidant and antimicrobial activities. Antimicrobial studies revealed the more noxious nature of metal complexes compared to ligand against various strains of bacteria and fungi. Molecular docking results based on the binding energy values also supported the experimental results of the antioxidant activities of the compounds. HL was found to be a better antioxidant than metal complexes. For a better insight into the structure, computational studies of the compounds were also carried out. A clear intra-molecular charge transfer was perceived in the ligand and its metal complexes. The transfer integral values for holes (36.48 meV) were found to be higher than the electron transfer integrals (24.76 meV), which indicated that the ligand would be a better hole transporter. According to the frontier molecular orbitals of the dimer, the charge transfer within the molecule is found from monomer 1 to 2., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Forests are at increasing risk from pathogen outbreak. Climate change for example enhance the risk of local disease outbreaks, and naturalization of exotic pathogens may follow human activities, warranting robust pest surveillance routines to support forest management. Melampsora pinitorqua (pine twisting rust) is of concern in Swedish forestry, and here we evaluate the use of visible rust scores (VRS) on its obligate summer host, European aspen (Populus tremula) as a tool for quantification of the pathogen. With use of species-specific primers, we could detect the native rust, but we failed to detect two exotic rusts (M. medusae and M. larici-populina). We found that aspen genotype determined the presence of fungal genetic markers (amplifying the ITS2 region of the fungal rDNA sequence) as well as DNA sequences specific to M. pinitorqua. We correlated VRS with the amount of fungal DNA in the same leaf, and we related the findings to aspen genotype-specific parameters such as the ability to synthesize and store leaf condensed tannins (CT). At the genotype level both positive and negative relationships were observed between CTs, fungal markers, and rust infestations. However, at the population level, foliar CT concentrations correlated negatively with general fungal- and rust-specific marker abundances. Our results, therefore, do not support the use of VRS to assess Melampsora infestation in Aspen. They do, however, suggest that the relationship between European aspen and rust infestation may be characterized as autochthonous in northern Sweden., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Siddique, Menke, Dinedurga and Albrectsen.)

A Schiff base ligand HL, ( E )-2-((adamantan-1-ylimino)methyl)-6-allylphenol, was synthesized by condensation of amantadine with 3-allyl-2-hydroxybenzaldehyde, followed by the synthesis of its Zn(ii), Co(ii), Cr(iii), and VO(iv) complexes under reflux conditions. The synthesized compounds were comprehensively elucidated by using different spectroscopic and analytical techniques: UV-Vis, 1 H and 13 C-NMR, FT-IR, ESI-MS, thermal, and single-crystal XRD analysis. The chemical composition of the synthesized compounds was also verified by molar conductance and elemental analysis. An octahedral geometry for Cr(iii) and Co(ii) complexes, tetrahedral for Zn(ii) complex, and square pyramidal geometry have been proposed for VO(iv) complexes. The antidiabetic activities of the synthesized compounds were also evaluated by performing in vitro α-amylase and α-glucosidase inhibition studies. The Co(ii) complex exhibited the highest α-glucosidase inhibitory activity, whereas oxovanadium(iv) and zinc(ii) complexes were also found to be effective against α-amylase. In alkaline phosphatase (ALP) inhibition studies, the HL was found to be inactive, while the complexes showed remarkable enzyme inhibition in the following order: VO > Zn > Co, in a concentration-dependent manner., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Tomato ( Solanum lycopersicum L.) is a popular nutritious vegetable crop grown in Malaysia and other parts of the world. However, fungal diseases such as anthracnose pose significant threats to tomato production by reducing the fruit quality and food value of tomato, resulting in lower market prices of the crop globally. In the present study, the etiology of tomato anthracnose was investigated in commercial tomato farms in Sabah, Malaysia. A total of 22 fungal isolates were obtained from anthracnosed tomato fruits and identified as Colletotrichum species, using morphological characteristics. The phylogenetic relationships of multiple gene sequence alignments such as internal transcribed spacer (ITS), β-tubulin ( tub2 ), glyceraldehyde 3-phosphate dehydrogenase ( gapdh ), actin ( act ), and calmodulin ( cal ), were adopted to accurately identify the Colletotrichum species as C. truncatum . The results of pathogenicity tests revealed that all C. truncatum isolates caused anthracnose disease symptoms on inoculated tomato fruits. To our knowledge, the present study is the first report of tomato anthracnose caused by C. truncatum in Malaysia. The findings of this study will be helpful in disease monitoring, and the development of strategies for effective control of anthracnose on tomato fruits.

The current study investigates the antioxidant, antidiabetic, hepatoprotective, and nephroprotective potentials of a polyherbal mixture containing the methanolic extracts of seeds from Nigella sativa , Cicer arietinum , Silybum marianum , and Citrullus colocynthis and the rhizome of Zingiber officinale . The polyherbal extract (PHE) showed significant total phenolic contents (187.17 GAE/g), ferric reducing power (28%), and radical-scavenging activity (86.16%). The PHE also showed a substantial hypoglycemic effect in alloxan-induced diabetic rats by reducing the blood glucose level of the PHE-treated rats (-48.64%) and increasing the insulin level (107.5%) as compared with the diabetic control group. Likewise, an increase in high-density lipoprotein (HDL) contents (22.95%) with an associated decrease in low-density lipoprotein (LDL) levels (-43.93%) was also noted. A significant decrease in serum levels of liver marker enzymes, e.g. , SGPT (-36%), SGOT (-31%), and serum ALP (-12%), was also observed as compared with the standard drug-treated group. Based on the findings of the study, it may be suggested that PHE helps ameliorate the severity of diabetes as a herbal remedy and might be employed in nutra-pharmaceuticals, replacing synthetic antidiabetic compounds., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The application of polyploidy in sustainable agriculture has already brought much appreciation among researchers. Polyploidy may occur naturally or can be induced in the laboratory using chemical or gaseous agents and results in complete chromosome nondisjunction. This comprehensive review described the potential of polyploidization on plants, especially its role in crop improvement for enhanced production and host-plant resistance development against pests and diseases. An in-depth investigation on techniques used in the induction of polyploidy, cytogenetic evaluation methods of different ploidy levels, application, and current research trends is also presented. Ongoing research has mainly aimed to bring the recurrence in polyploidy, which is usually detected by flow cytometry, chromosome counting, and cytogenetic techniques such as fluorescent in situ hybridization (FISH) and genomic in situ hybridization (GISH). Polyploidy can bring about positive consequences in the growth and yield attributes of crops, making them more tolerant to abiotic and biotic stresses. However, the unexpected change in chromosome set and lack of knowledge on the mechanism of stress alleviation is hindering the application of polyploidy on a large scale. Moreover, a lack of cost-benefit analysis and knowledge gaps on the socio-economic implication are predominant. Further research on polyploidy coupling with modern genomic technologies will help to bring real-world market prospects in the era of changing climate. This review on polyploidy provides a solid foundation to do next-generation research on crop improvement.

Due to the severe side effects revealed by most of the currently used antidiabetic medicines, search for finding new and safe drugs to manage diabetes is continued. Naphthoquinones possessing strong antioxidant properties have been employed as candidates for diabetes therapy. Present study is aimed at finding the antioxidant and hypoglycaemic potential of some novel derivatives of 2-phenylamino-1,4-naphthoquinones (PAN) including chloro, nitro, methyl and bromo (5a-d) derivatives synthesized by single pot experiment. Product crystals were purified by TLC and characterized by FT-IR. The antioxidant potential of the compounds was assayed through DPPH radical scavenging and reducing power activities noted as UV-vis. absorbance. The DPPH assay has showed the powerful antioxidant activity of nitro and bromo derivatives, while the nitro derivative showed the significant reduction potential towards FRAP assay. Hypoglycaemic potential of the compounds was studied in rat animal model. All synthesized compounds revealed better hypoglycaemic activity; however, the chloro-derivative exhibited the more potent hypoglycaemic activity showing about 43% reduction in the mean blood glucose levels of the treated animals. As the bioreduction of naphthoquinones may be influenced by changing its redox properties, it has been noticed that the e-donating resonance effect (+R) of 'chloro' group has shown the significant effects on biological activity through stabalization of its imine form which limits the potential of generation of free radicals during bioreduction of quinones and thus has been proposed as the reason of its hypoglycaemic activity. Future studies employing the properties of e-donating groups of PAN may optimize the drug-receptor interaction for better drug designing and drug development strategies against diabetes and also for the clinical trials.

Triple negative breast cancer (TNBC) heterogeneity and limited therapeutic options confer its phenotypic aggressiveness. The discovery of anti-TNBC natural products with valid molecular target(s) and defined pharmacodynamic profile would facilitate their therapeutic nutraceutical use by TNBC patients. The extra-virgin olive oil (EVOO) is a key Mediterranean diet ingredient. S -(-)-Oleocanthal (OC) leads the bioactive anti-tumor EVOO phenolic ingredients. A previous study reported the solid dispersion formulated OC with (+)-xylitol (OC-X) suppressed the in vivo progression and recurrence of the TNBC MDA-MB-231 cells. This study investigates the ability of OC-X formulation to suppress the in vivo heterogeneous BC initiation and progression utilizing advanced preclinical transgenic MMTV-PyVT and TNBC PDX mouse models. Furthermore, the clustering of the gene expression profiles in MMTV-PyVT and PDX mouse tumors treated with OC-X acquired by a Clariom S microarray analysis identified the distinctly affected genes. Several affected novel signature genes identified in response to OC-X treatments and proved overlapped in both mouse and human tumor models, shedding some lights toward understanding the OC anticancer molecular mechanism and assisting in predicting prospective clinical outcomes. This study provides molecular and preclinical evidences of OC-X potential as a nutraceutical suppressing heterogeneous TNBC model and offers preliminary gene-level therapeutic mechanistic insights.

Mycoviruses, just as the fungal endophytes they infect, are ubiquitous biological entities on Earth. Mycoviruses constitute a diverse group of viruses, and metagenomic approaches have-through recent discoveries of been mycoviruses-only recently began to provide evidence of this astonishing diversity. The current review presents (1) various mycoviruses which infect fungal endophytes and forest pathogens, (2) their presumed origins and interactions with fungi, plants and the environment, (3) high-throughput sequencing techniques that can be used to explore the horizontal gene transfer of mycoviruses, and (4) how the hypo- and hypervirulence induced by mycoviral infection is relevant to the biological control of pathogenic fungi.

Lung cancer (LC) represents the topmost mortality-causing cancer in the U.S. LC patients have overall poor survival rate with limited available treatment options. Dysregulation of the mesenchymal epithelial transition factor (c-MET) and cyclooxygenase 2 (COX2) initiates aggressive LC profile in a subset of patients. The Mediterranean extra-virgin olive oil (EVOO)-rich diet already documented to reduce multiple malignancies incidence. (-)-Oleocanthal (OC) is a naturally occurring phenolic secoiridoid exclusively occurring in EVOO and showed documented anti-breast and other cancer activities via targeting c-MET. This study shows the novel ability of OC to suppress LC progression and metastasis through dual targeting of c-MET and COX-2. Western blot analysis and COX enzymatic assay showed significant reduction in the total and activated c-MET levels and inhibition of COX1/2 activity in the lung adenocarcinoma cells A549 and NCI-H322M, in vitro. In addition, OC treatment caused a dose-dependent inhibition of the HGF-induced LC cells migration. Daily oral treatment with 10 mg/kg OC for 8 weeks significantly suppressed the LC A549-Luc progression and prevented metastasis to brain and other organs in a nude mouse tail vein injection model. Further, microarray data of OC-treated lung tumors showed a distinct gene signature that confirmed the dual targeting of c-MET and COX2. Thus, the EVOO-based OC is an effective lead with translational potential for use as a prospective nutraceutical to control LC progression and metastasis.

Epidemiological and clinical studies compellingly showed the ability of Mediterranean diet rich in extra-virgin olive oil (EVOO) to reduce multiple diseases such as cancer, cardiovascular diseases, and aging cognitive functions decline. The S -(-)-Oleocanthal (OC) is a minor phenolic secoiridoid exclusively found in extra-virgin olive oil (EVOO). OC recently gained notable research attention due to its excellent in vitro and in vivo biological effects against multiple cancers, inflammations, and Alzheimer's disease. However, OC safety has not been comprehensively studied yet. This study reports for the first time the detailed safety of oral single OC dose in Swiss albino mice, applying the OECD 420 procedure. Male and female Swiss albino mice ( n = 10) were orally treated with a single OC dose of either 10, 250, or 500 mg/kg bodyweight or equivalent volumes of distilled water. Mice fed a regular diet, and carefully observed for 14 days. Further, mice were then sacrificed, blood samples, and organs were collected and subjected to hematological, biochemical, and histological examinations. OC 10 mg/kg oral dose appears to be without adverse effects. Further, 250 mg/kg OC, p.o., is suggested as a possible upper dose for preclinical studies in the future., Competing Interests: K. El Sayed is a Co-founder and Medicinal Chemistry Chief Scientific Officer without compensation in the Shreveport, Louisiana-based Oleolive.

A novel bisegmented double-stranded RNA virus was identified in the mycoparasitic and opportunistic fungus Hypomyces chrysospermus. The RNA1 genome segment comprises 1866 bp and encodes an RNA-dependent RNA polymerase (RdRp). The RNA2 segment comprises 1822 bp and encodes a capsid protein. Phylogenetic analysis of the RdRp protein indicated that this virus is a new member of genus Alphapartitivirus in the family Partitiviridae. We have designated this mycovirus as "Hypomyces chrysospermus partitivirus 1" (HcPV1). HcPV1 is highly transmissible with aleurioconidia and is present in large amounts within growing mycelium in comparison to the GAPDH reference gene.

Breast cancer (BC) recurrence represents a challenge for survivors who have had their primary tumors surgically excised, and/or have completed radiation, neoadjuvant, or adjuvant therapeutic regimens. Current BC treatments mostly lack the ability to reduce the risk of disease recurrence. About 70% of BC patients will subsequently suffer disease relapse, manifesting as local, regional, or distant tumor recurrence, which clearly underscores the urgent need to discover novel recurrence inhibitors. (-)-Oleocanthal (OC) is a natural phenolic, found so far exclusively in extra-virgin olive oil (EVOO). OC exerts documented bioactivities against diverse cancer types, inflammation, and neurodegenerative diseases. Herein we report the novel activity of daily oral treatment with OC (10 mg/kg) in preventing BC locoregional recurrence in a nude mouse xenograft model generated by orthotopic inoculation with BT-474 cells as a luminal type B model. We further report inhibition of tumor recurrence by OC after completion of a lapatinib neoadjuvant regimen. However, in a recurrence model of triple-negative breast cancer (TNBC), OC treatment (10 mg/kg) did not effectively prevent tumor recurrence, but rather, was seen to significantly reduce the growth of recurrent tumors as compared to vehicle control-treated animals. Inhibition of tumor recurrence was associated with significant serum level reductions of the human BC recurrence marker CA 15-3 at the study end in animals treated with OC. OC treatment upregulated the expression of the epithelial marker E-cadherin and downregulated the levels of the mesenchymal marker vimentin in recurrent tumors vs. untreated control animals. OC treatment also reduced the activation of MET and HER2 receptors, as indicated by reduced phosphorylation levels of these proteins in recurrent tumors vs. controls. Collectively, the results of our studies provide the first evidence for suppression of BC tumor recurrence by oral OC treatment in an animal model for such recurrence, and furthermore, highlight favorable prospects for this natural product to emerge as a first-in-class BC recurrence inhibitor.

Dysregulation of epidermal growth factor receptor (EGFR)/human epidermal growth factor-2 (HER2) family is a hallmark of aggressive breast cancer. Small-molecule tyrosine kinase inhibitors are among the most effective cancer targeted treatments. (-)-Oleocanthal (OC) is a naturally occurring phenolic secoiridoid lead from extra-virgin olive oil with documented anti-cancer activities via targeting mesenchymal epithelial transition factor (c-Met). Dysregulation of c-Met promotes aggressiveness to breast cancer-targeted therapies. Lapatinib (LP) is an FDA-approved dual EGFR/HER2 inhibitor for HER2-amplified breast cancer. HER2-Positive tumor cells can escape targeted therapies like LP effects by overexpressing c-Met. Combined OC-LP treatment is hypothesized to be mechanistically synergistic against HER2-overexpressing breast cancer. Combined sub-effective treatments of OC-LP resulted in synergistic anti-proliferative effects against the HER2-positive BT-474 and SK-BR-3 breast cancer cell lines, compared to OC or LP monotherapy. Antibody array and Western blot analysis showed that combined OC-LP treatment significantly inhibited EGFR, HER2, and c-Met receptor activation, as well as multiple downstream signaling proteins, compared to individual OC or LP treatment. OC-LP Combination significantly inhibited invasion and migration of breast cancer cells through reduced activation of focal adhesion kinase (FAK) and paxillin. Combined treatment of OC-10 mg/kg with LP-12.5 mg/kg suppressed more than 90% of BT-474 tumor cells growth in a nude mouse xenograft model, compared to individual OC or LP treatment. Activated c-Met, EGFR, HER2, and protein kinase B (AKT) were significantly suppressed in combination-treated mice tumors, compared to OC or LP monotherapy. This study reveals the OC future potential as combination therapy to sensitize HER2-overexpressing breast cancers and significantly reduce required doses of targeted HER family therapeutics.

Complex networks are the subject of fundamental interest from the scientific community at large. Several metrics have been introduced to characterize the structure of these networks, such as the degree distribution, degree correlation, path length, clustering coefficient, centrality measures, etc. Another important feature is the presence of network symmetries. In particular, the effect of these symmetries has been studied in the context of network synchronization, where they have been used to predict the emergence and stability of cluster synchronous states. Here, we provide theoretical, numerical, and experimental evidence that network symmetries play a role in a substantially broader class of dynamical models on networks, including epidemics, game theory, communication, and coupled excitable systems; namely, we see that in all these models, nodes that are related by a symmetry relation show the same time-averaged dynamical properties. This discovery leads us to propose reduction techniques for exact, yet minimal, simulation of complex networks dynamics, which we show are effective in order to optimize the use of computational resources, such as computation time and memory.

The failure of chemotherapy especially in triple negative breast cancer (TNBC) patients has been correlated with the overexpression of the mesenchymal-epithelial transition factor (c-Met) receptor. Thus, the hepatocyte growth factor (HGF)/c-Met signaling axis has gained considerable attention as a valid molecular target for breast cancer therapy. This study reports for the first time the discovery of the 13 1 -oxophorbines pheophorbide A and protopheophorbide A along with chlorophyllide A from Ziziphus lotus, an edible typical Tunisian plant, as the potent antiproliferative compounds against the human breast cancer cells MDA-MB-231 and MCF-7. Compared to other compounds, protopheophorbide A exerted the highest light-independent antiproliferative effect against the metastatic TNBC MDA-MB-231 cells (IC 50  = 6.5 μM). In silico, this compound targeted the kinase domain of multiple c-Met crystal structures. It potently inhibited the kinase domain phosphorylation of wild and mutant c-Met in Z-LYTE kinase assay. Protopheophorbide A inhibited HGF-induced downstream c-Met-dependent cell proliferation, survival, adhesion and migration through RAF/MEK/ERK and PI3K/PTEN/AKT signaling pathways modulation, ROS generation and activation of JNK and p38 pathways. Interestingly, this compound impaired the ability of the MDA-MB-231 cells to adhere at different extracellular matrix proteins by reducing the HGF-induced expression of integrins αv, β3, α2, and β1. Moreover, protopheophorbide A exhibited anti-migratory properties (IC 50  = 2.2 μM) through impacting the expression levels of E-cadherin, vimentin, β-catenin, FAK, Brk, Rac, and Src proteins. Importantly, treatment with protopheophorbide A significantly inhibited the MDA-MB-231 tumor growth in vivo. Our results suggest that protopheophorbide A could be a novel c-Met inhibitory lead with promise to control c-Met/HGF-dependent breast malignancies., (© 2018 Wiley Periodicals, Inc.)