Metabolic profiling, antimicrobial, anticancer, and in vitro and in silico immunomodulatory investigation of Aspergillus niger OR730979 isolated from the Western Desert, Egypt.

Ten fungal species were isolated from soil in the Western Desert and Wadi El-Natron in Egypt. All fungal isolates were morphologically recognized down to the species level. Methanol extracts of fungal mycelia and ethyl acetate extracts of culture filtrate from the isolated fungi were evaluated for antimicrobial activity against six pathogenic bacteria and one pathogenic yeast (Candida albicans ATCC20231). Only ethyl acetate extracts of Fusarium circinatum, Aspergillus niger, and Aspergillus terreus culture filtrates showed significant antimicrobial activity against the majority of the investigated pathogens. The culture filtrate extract of Aspergillus niger exhibited notable cytotoxicity towards the breast cancer (MCF-7) cell line, with the lowest detected IC50 recorded at 8 µg/µl. Whereas Fusarium circinatum and Aspergillus terreus had IC50s of 15.91 µg/µl and 18 µg/µl, respectively. A gas chromatography-mass spectroscopy (GC-MS) investigation of A. niger's potent extract revealed 23 compounds with different biological activities. Glycidyleoleate was found to be the main extract component. Aspergillus niger extract was chosen to study its possible cytotoxic mechanism. The extract was found to induce apoptosis and cell cycle arrest at the < 2n stage. Despite a significant increase in caspases 8 and 9, the production levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) have shown a significant decrease. The high interaction of glycidyleoleate against the studied cytokines' binding receptors was demonstrated via docking studies. In conclusion, the available data revealed that the culture filtrate extract of A. niger possesses promising antimicrobial, cytotoxic, and immunomodulatory properties.

Early cancer detection using the fluorescent Ashwagandha chitosan nanoparticles combined with near-infrared light diffusion characterization: in vitro study.

Early cancer diagnosis through characterizing light propagation and nanotechnology increases the survival rate. The present research is aimed at evaluating the consequence of using natural nanoparticles in cancer therapy and diagnosis. Colon cancer cells were differentiated from the normal cells via investigating light diffusion combined with the fluorescence effect of the Ashwagandha chitosan nanoparticles (Ash C NPs). Ionic gelation technique synthesized the Ash C NPs. High-resolution transmission electron microscope, dynamic light scattering, and zeta potential characterized Ash C NPs. Fourier transform infrared spectroscopy analyzed Ash C NPs, chitosan, and Ashwagandha root water extract. Moreover, the MTT assay evaluated the cytotoxicity of Ash C NPs under the action of near-infrared light (NIR) irradiation. The MTT assay outcomes were statistically analyzed by Bonferroni post hoc multiple two-group comparisons using one-way variance analysis (ANOVA). Based on the Monte-Carlo simulation technique, the spatially resolved steady-state diffusely reflected light from the cancerous and healthy cells is acquired. The diffuse equation reconstructed the optical fluence rate using the finite element technique. The fluorescent effect of the nanoparticles was observed when the cells were irradiated with NIR. The MTT assay revealed a decrease in the cell viability under the action of Ash C NPs with and without laser irradiation. Colon cancer and normal cells were differentiated based on the optical characterization after laser irradiation. The light diffusion equation was successfully resolved for the fluence rate on cells' surfaces showing different normal and cancer cells values. Ash C NPs appeared its fluorescent effect in the presence of NIR laser.

The Fluorescent Effect of Withania Somnifera Chitosan Nanocomposite as an Effective Contrast Agent for Cancer Theragnostic: Experimental Study in Vitro.

Nanomedicine and fluorescent optical imaging are effective in early cancer detection. The current study synthesized biocompatible nanocomposites from natural biomaterials towards inexpensive and safe cancer theragnostic. Two forms of nanocomposites were synthesized using the ionic gelation method: 1. Chitosan/ Withania Somnifera /tripolyphosphate nanocomposites, 2. Withania Somnifera/Chitosan nanocomposites. The nanocomposites were characterized by dynamic light scattering, zeta potential, and the transmission electron microscope. Fourier transform infrared spectroscopy analyzed the Withania Somnifera root water extract, Chitosan, and the synthesized nanocomposites. The cytotoxicity of the nanocomposites was investigated against the colon cancer cells (Caco2 cells) in the absence and the presence of laser (665 nm, 5 mW) irradiation. MTT assay evaluated the cytotoxicity, and Trypan blue assay assessed the cell viability. Cancerous cells were photographed under the inverted microscope in the presence and the absence of laser irradiation. Results were analyzed statistically using one-way variance (ANOVA) analysis with Bonferroni post-Hoc multiple two-group comparisons. The characterization results ensured the successful synthesis of Withania Somnifera/Chitosan nanocomposites. The results showed an increase in the cytotoxicity against colon carcinoma and a decrease in cell viability in the presence and absence of Near-infrared laser irradiation under the action of nanocomposites. The cytotoxicity of the synthesized nanocomposites increased by exposing the cells to the laser. The shining light of the nanocomposites appeared on the cells photographed under the inverted microscope. The synthesized natural nanocomposites promise systemic cytotoxicity will be efficient in molecular imaging in vivo applications.

Hydroxyapatite nanocomposite as a potential agent in osteosarcoma PDT.

Using Nanoplatforms as a hauler for photosensitizers is a bespoke paradigm to improve its bioavailability and to boost the PDT efficacy. Herein, the photodynamic cytotoxicity of methylene blue (MB) loaded on hydroxyapatite nanoparticles (HA-NPs) was tested against human osteosarcoma-derived cells (Saos-2 cell line). HA-NPs and HA-NPs loaded with MB (HA-NPs-MB) were prepared by a chemical precipitation method and characterized by TEM, Zeta potential, FTIR, and XRD. TEM images revealed that HA-NPs have a rod shape with a diameter of 14-17 nm and length around 46-64 nm. FTIR and Zeta potential confirmed the adsorption of cationic MB on HA-NPs. XRD pattern was identical to the standard XRD pattern of HA-NPs. Incubation of Saos-2 cells (24 h) with HA-NPs-MB then irradiation of cells (5 min) with a diode laser (808 nm), causes a higher decrement of cell viability (determined by MTT assay) than that caused by free MB. The LC50 was 57.53 µg/mL and 86.99 µg/mL for HA-NPs-MB and free MB, respectively. Thus, the nanoformulation of MB greatly reduced the dose of MB required for effective PDT. This study also investigated the mode of cell death after incubation of cells with free MB or HA-NPs-MB composite then exposure to laser radiation. The results revealed that the majority of cells died by apoptosis while a minor fraction of cells died by necrosis, especially in the case of HA-NPs-MB. Levels of caspase-3 and death receptor-4 (DR-4) were more elevated in the case of HA-NPs-MB than free MB. The effect of the prepared nanocomposite and free MB on Raw murine macrophage (RAW 264.7) viability was also examined using the MTT assay. The results indicated that HA-NPs-MB in the presence of laser has a great cytotoxic effect on macrophage cells compared to other treatments. This may present an advantage through decreasing macrophage that promotes tumor growth. In conclusion, HA-NPs-MB nanocomposite surmounts free MB and HA-NPs in destroying macrophage cells and Saos-2 cells through apoptosis in the presence of laser irradiation. This study introduces a thorough and new insight on osteosarcoma (cancer cell line Saos-2) PDT using HA-NPs-MB exploiting the biosafety of HA-NPs.

New benzenesulfonamide scaffold-based cytotoxic agents: Design, synthesis, cell viability, apoptotic activity and radioactive tracing studies.

A new series of thiazolidinone (5a-g), thiazinone (9a-g) and dithiazepinone (9a-g) heterocycles bearing a benzenesulfonamide scaffold was synthesized. Cytotoxicity of these derivatives was assessed against MCF-7, HepG2, HCT-116 and A549 cancer cell lines and activity was compared to the known cytotoxic agents doxorubicin and 5-FU where the most active compounds displayed better to nearly similar IC50 values to the reference compounds. For assessing selectivity, the most active derivatives against MCF-7, 5b, 5c and 5e, were also assessed against the normal breast cell line MCF-10 A where they demonstrated high selective cytotoxicity to cancerous cells over that to normal cells. Further, the effect of the most active compounds 5b-e on MCF-7 and HepG2 cell cycle phase distribution was assessed and the tested sulfonamide derivatives were found to induce accumulation of cells in the <2n phase. To further confirm apoptosis induction, caspase 8 and 9 levels in MCF-7 and HepG2 were evaluated before and after treatment with compounds 5b-e and were found to be significantly higher after exposure to the test agents. Since 5c was the most active, its effect on the cell cycle regulation was confirmed where it showed inhibition of the CDK2/cyclin E1. Finally, in vivo biodistribution study using radioiodinated-5c revealed a significant uptake and targeting ability into solid tumor in a xenograft mouse model.

Toward Highly Efficient Cancer Imaging and Therapy Using the Environment-Friendly Chitosan Nanoparticles and NIR Laser.

Chitosan-tripolyphosphate nanoparticles (C-TPP NPs) were synthesized to investigate their cytotoxicity against colon cancer cells (Caco2 cells) in the absence and the presence of a near-infrared (NIR) laser to evaluate their influence in cancer detection using the NIR laser and to evaluate the NIR laser on cancer treatment. The synthesized NPs were characterized by Fourier transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS), zeta potential (ZP), and transmission electronic microscope (TEM). The cytotoxicity was analyzed by the MTT test and the cell viability was assessed using the Trypan blue method. C-TPP NPs showed increased cytotoxicity and decreased cell viability against Caco2 cells. Upon laser exposure only, the cell viability decreased. The C-TPP NPs appeared to have a shining light on the cancerous cells which were photographed under the inverted microscope.

Design, synthesis and biological evaluation of some novel sulfonamide derivatives as apoptosis inducers.

Several novel thiazolidinone and fused thiazolidinone derivatives bearing benzenesulfonamide moiety were synthesized and confirmed via spectral and elemental analyses. The newly synthesized compounds were evaluated for their cytotoxic activity on colorectal cancer cell line (Caco-2). All the synthesized compounds showed better activity than the reference standards (Doxorubicin and 5-FU). Investigation of the apoptotic activity of the most active compounds revealed that compounds 3a, 5a, 5c and 6c activate both caspase-3 and Fas-ligand in Caco-2 cell line. Compound 3a was the most active compound with caspase-3 concentration of 0.43 nmol/mL and Fas-ligand concentration of 775.2 pg/mL in treated Caco-2 cells. Compound 3a was radiolabeled with 99mTc and its biodistribution pattern was evaluated in vivo using normal Swiss Albino mice. 99mTc-compound 3a complex didn't exhibit any accumulation in any body organs except for its accumulation in the colon; target organ; where it showed 8.97 ± 1.35 %ID/g at 15min p. i. that elevated till 16.02 ± 2.43 %ID/g at 120min p. i.

Naringenin attenuates cisplatin nephrotoxicity in rats.

The effect of naringenin (NAR), a naturally occurring citrus flavanone, on the acute nephrotoxicity produced by cisplatin (7 mg/kg, i.v.) was investigated in the rat. Oral administration of NAR (20 mg/kg/day) for 10 days, starting 5 days before cisplatin single i.v. injection, produced significant protection of renal function. NAR reduced the extent of cisplatin-induced nephrotoxicity, as evidenced by significant reduction in serum urea and creatinine concentrations, decreased polyuria, reduction in body weight loss, marked reduction in urinary fractional sodium excretion and glutathione S-transferase (GST) activity, and increased creatinine clearance. Cisplatin-induced alterations in renal cortex lipid peroxides and GST activity were markedly improved by NAR. Cisplatin-induced alterations in renal cortex antioxidant defense system were greatly prevented by NAR. In cisplatin-NAR combined treatment group, antioxidant enzymes namely superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were significantly increased to 54.5, 30.3 and 35.6%, respectively compared to cisplatin treated group. Platinum renal content was not affected by NAR treatment. The results provide further insight into the mechanisms of cisplatin-induced nephrotoxicity and confirm the antioxidant potential of NAR.