The treatment of drug-resistant cancer is a clinical challenge, hence screening for novel anticancer drugs is critically important. In the present study we investigated the anti-tumor potential of three plant-derived flavone compounds 3-hydroxy flavone (3-HF), 6-hydroxy flavone (6-HF) and 7-hydroxy flavone (7-HF) either alone or combined with silica nanoparticles (3-HF+NP, 6-HF+NP and 7-HF+NP) on the human breast carcinoma cell lines MDA-MB-231 and MCF-7, as well as on non-tumorigenic normal breast epithelial cells (MCF-10). The IC50 values of these flavone compounds loaded with NP (flavones+NP) in these cell lines were determined to be 1.5µg/ml without affecting the viability of normal MCF-10 cells. Additionally, we found that combination of flavones with NP significantly induced apoptosis in MCF-7 and MDA-MB-231 cancer cells using annexin-V/PI double staining followed by flow cytometry analysis. Furthermore, flavones+NP increased the expression of cytochrome C and caspase 9 mediating growth arrest of these cancer cells. Most importantly, combination of flavones with NP significantly abolished the expression of ATF-3, which in turn is responsible for the proliferation and invasion of bone metastatic breast cancer cells. Our data revealed the potential therapeutic effects of these flavones in fighting breast cancer cells and provided the first insight concerning the underlying molecular mechanisms.

The treatment of drug-resistant cancer is a clinical challenge, hence screening for novel anticancer drugs is critically important. In the present study we investigated the anti-tumor potential of three plant-derived flavone compounds 3-hydroxy flavone (3-HF), 6-hydroxy flavone (6-HF) and 7-hydroxy flavone (7-HF) either alone or combined with silica nanoparticles (3-HF+NP, 6-HF+NP and 7-HF+NP) on the human breast carcinoma cell lines MDA-MB-231 and MCF-7, as well as on non-tumorigenic normal breast epithelial cells (MCF-10). The IC50 values of these flavone compounds loaded with NP (flavones+NP) in these cell lines were determined to be 1.5µg/ml without affecting the viability of normal MCF-10 cells. Additionally, we found that combination of flavones with NP significantly induced apoptosis in MCF-7 and MDA-MB-231 cancer cells using annexin-V/PI double staining followed by flow cytometry analysis. Furthermore, flavones+NP increased the expression of cytochrome C and caspase 9 mediating growth arrest of these cancer cells. Most importantly, combination of flavones with NP significantly abolished the expression of ATF-3, which in turn is responsible for the proliferation and invasion of bone metastatic breast cancer cells. Our data revealed the potential therapeutic effects of these flavones in fighting breast cancer cells and provided the first insight concerning the underlying molecular mechanisms.

The treatment of drug-resistant cancer is a clinical challenge, hence screening for novel anticancer drugs is critically important. In the present study we investigated the anti-tumor potential of three plant-derived flavone compounds 3-hydroxy flavone (3-HF), 6-hydroxy flavone (6-HF) and 7-hydroxy flavone (7-HF) either alone or combined with silica nanoparticles (3-HF+NP, 6-HF+NP and 7-HF+NP) on the human breast carcinoma cell lines MDA-MB-231 and MCF-7, as well as on non-tumorigenic normal breast epithelial cells (MCF-10). The IC50 values of these flavone compounds loaded with NP (flavones+NP) in these cell lines were determined to be 1.5µg/ml without affecting the viability of normal MCF-10 cells. Additionally, we found that combination of flavones with NP significantly induced apoptosis in MCF-7 and MDA-MB-231 cancer cells using annexin-V/PI double staining followed by flow cytometry analysis. Furthermore, flavones+NP increased the expression of cytochrome C and caspase 9 mediating growth arrest of these cancer cells. Most importantly, combination of flavones with NP significantly abolished the expression of ATF-3, which in turn is responsible for the proliferation and invasion of bone metastatic breast cancer cells. Our data revealed the potential therapeutic effects of these flavones in fighting breast cancer cells and provided the first insight concerning the underlying molecular mechanisms.

Protein A (SpA) of Staphylococcus aureus is known to target the paratope of immunoglobulins expressing V(H)3 genes, and to delete marginal zone B cells and B-1a in vivo. We have discovered that SpA endows S. aureus with the potential to subvert B-cell trafficking in the host. We found that SpA, whose Fc-binding site has been inactivated, binds essentially to naïve B cells and induces a long-lasting decrease in CXCR4 expression and in B-cell chemotaxis to CXCL12. Competition experiments indicated that SpA does not interfere with binding of CXCR4 ligands and does not directly bind to CXCR4. This conclusion is strongly supported by the inability of SpA to modulate clathrin-mediated CXCR4 internalization, which contrasts with the potent effect of anti-immunoglobin M (IgM) antibodies. Microscopy and biochemical experiments confirmed that SpA binds to the surface IgM/IgD complex and induces its clathrin-dependent internalization. Concomitantly, the SpA-induced signaling leads to protein kinase C-dependent CXCR4 downmodulation, suggesting that SpA impairs the recycling of CXCR4, a postclathrin process that leads to either degradation into lysozomes or de novo expression at the cell surface. In addition to providing novel insight into disruption of B-cell trafficking by an infectious agent, our findings may have therapeutic implications. Because CXCR4 has been associated with cancer metastasis and with certain autoimmune diseases, SpA behaves as an evolutionary tailored highly specific, chemokine receptor inhibitor that may have value in addition to conventional cytotoxic therapy in patients with various malignancies and immune-mediated diseases.

In multiple myeloma (MM), malignant plasma cells reside in the bone marrow, where they accumulate in close contact with
stromal cells. The mechanisms responsible for the chemotaxis of malignant plasma cells are still poorly understood. Thus,
we investigated the mechanisms involved in the chemotaxis of MDN and XG2 MM cell lines. Both cell lines strongly
expressed CCR9, CXCR3 and CXCR4 chemokine receptors but only migrated toward CXCL12. Activation of CXCR4 by CXCL12
resulted in the association of CXCR4 with CD45 and activation of PLCb3, AKT, RhoA, IkBa and ERK1/2. Using siRNA-silencing
techniques, we showed CD45/CXCR4 association is essential for CXCL12-induced migration of MM cells. Thymoquinone
(TQ), the major active component of the medicinal herb Nigella sativa Linn, has been described as a chemopreventive and
chemotherapeutic compound. TQ treatment strongly inhibited CXCL12-mediated chemotaxis in MM cell lines as well as
primary cells isolated from MM patients, but not normal PBMCs. Moreover, TQ significantly down-regulated CXCR4
expression and CXCL12-mediated CXCR4/CD45 association in MM cells. Finally, TQ also induced the relocalization of
cytoplasmic Fas/CD95 to the membrane of MM cells and increased CD95-mediated apoptosis by 80%. In conclusion, we
demonstrate the potent anti-myeloma activity of TQ, providing a rationale for further clinical evaluation.

In this work, a novel voltammetric sensor was fabricated by the decoration of carboxylated multi-walled carbon
nanotubes (f-MWCNT) with gold nanoparticles (AuNPs) using glassy carbon paste (GCP) as a cross linker
(AuNPs/f-MWCNT/GCPE) for determination of cyproterone acetate (CPA) drug. Electrochemical behavior and
the surface characterization of the AuNPs/f-MWCNT/GCPE were investigated using scanning electron microscopy (SEM), cyclic voltammetry (CV) and square wave voltammetry (SWV). The modified electrode showed a
distinctive cathodic response towards CPA using SWV in phosphate buffer medium (pH 5.0) with a considerable
enhancement peak current (42 μA) compared to the bare GCPE (4 μA). Under the optimum conditions, the SWV
peak current of CPA increased linearly with its concentration at the range of 9.90 × 10−8 to 1.15 × 10-5 M with
a detection limit of 1.66 × 10−8 M (6.92 ng/mL) and calculated sensitivity of 92.93 μA μM–1 cm–2
. The modified
electrode displayed anti-interference ability against the physiological common interferents (i.e. ascorbic acid,
uric acid, alanine, cysteine, glucose, citric acid, uracil, and serine). Furthermore, the fabricated electrochemical
sensor displays a high sensitivity, good reproducibility, and long-term stability and it was effectively applied for
the determination of CPA in pharmaceutical products (Androcur) and in human blood serum and urine samples.

In this study, a new voltammetric nanosensor was constructed by the decoration of acetylene black (AB) with
gold nanoparticles (AuNPs) using glassy carbon paste (GCP) as a cross linker (nano-AB-AuNPs/GCPE) for determination of anticancer topotecan (TPT) drug. Moreover, from the response characteristics of cyclic voltammetry (CV) and square wave voltammetry (SWV), it was observed that TPT could be effectively accumulated at
nano-AB-AuNPs/GCPE and resulted in a sensitive anodic peak current in PBS of pH 6.0. The surface area,
electrical conductivity and catalytic performance of the modified electrode improved on account of the formation of nano-AB-AuNPs materials, thereby enhancing the sensitivity of the nanosensor. Under optimal conditions, a novel electrochemical method based on the nano-AB-AuNPs/GCPE sensor with high selectivity, high
sensitivity and high anti-interference ability was developed for the determination of TPT. Furthermore, the
electrochemical oxidation of TPT reveals an excellent linearity in the range of 1.99 × 10−9 to 6.71 × 10−7 M of
TPT with a detection limit of 1.64 × 10−11 M (6.91 × 10−3 ng/mL). The TPT as a preconcentration agent
showed chemical selectivity, so, the nanosensor was successfully applied for the determination of TPT in the
presence of high concentrations of uric acid. Moreover, the method was employed efficiently to detect TPT in
blood serum and urine samples, with satisfactory recoveries ranging from 98.16% to 100.76%.

We prove that conformable “fractional” differentiability of a function f:[0,∞[⟶R is nothing else than the classical differentiability. More precisely, the conformable α-derivative of f at some point x>0, where 0<α<1, is the pointwise product x^{1−α} f′(x). This proves the lack of significance of recent studies of the conformable derivatives. The results imply that interpreting fractional derivatives in the conformable sense alters fractional differential problems into differential problems with the usual integer-order derivatives that may no longer properly describe the original fractional physical phenomena. A general fractional viscoelasticity model is analysed to illustrate this state of affairs. We also test the modelling efficiency of the conformable derivative on various fractional models. We find that, compared with the classical fractional derivative, the conformable framework results in a substantially larger error.

Epinephrine (EP) is one of the important catecholamine neurotransmitters that play an important role in the mammalian
central nervous system. Therefore, it is necessary to determine the change of its concentrations. Nanoporous materials have
wide applications that include catalysis, energy storages, environmental pollution control, wastewater treatment, and sensing
applications. These unique properties could be attributable to their high surface area, a large pore volume, and uniform pore
sizes. A gold nanoporous layer modified gold electrode was prepared and applied for the selective determination of epinephrine
neurotransmitter at low concentration in the presence of several other substances including ascorbic acid (AA) and uric acid (UA).
The constructed electrode was characterized using scanning electron microscopy and cyclic voltammetry. The resulting electrode
showed a selective detection of epinephrine with the interferences of dopamine and uric acid over a wide linear range (from50

Epinephrine (EP) is one of the important catecholamine neurotransmitters that play an important role in the mammalian
central nervous system. Therefore, it is necessary to determine the change of its concentrations. Nanoporous materials have
wide applications that include catalysis, energy storages, environmental pollution control, wastewater treatment, and sensing
applications. These unique properties could be attributable to their high surface area, a large pore volume, and uniform pore
sizes. A gold nanoporous layer modified gold electrode was prepared and applied for the selective determination of epinephrine
neurotransmitter at low concentration in the presence of several other substances including ascorbic acid (AA) and uric acid (UA).
The constructed electrode was characterized using scanning electron microscopy and cyclic voltammetry. The resulting electrode
showed a selective detection of epinephrine with the interferences of dopamine and uric acid over a wide linear range (from50