Biocompatibility and radiosensitivity of a fiber optical-based dosimeter: biological applications.

This study introduces a cutting-edge fiber-optic dosimetry (FOD) sensor designed for measuring radiation in biological settings. The accuracy and precision of dosimeters for small animals, particularly prolonged exposure to nonuniform radiation fields, are always challenging. A state-of-the-art in-vivo dosimeter utilizing glass-encapsulated Thermoluminescence cylindrical detector (TLD) was introduced. The FODs are implanted into the rat during a prolonged irradiation scenario involving 137Cs where the rat has the freedom to move within a heterogeneous radiation domain. The implantation surgery was verified with X-ray computed tomography (CT) in addition to biochemical and pathological tests to assess the biocompatibility of FOD in vivo. A versatile FOD is designed for industrial and medical fields, which demand accurate and resilient radiation dosimeters. The dose measurements are associated with precise two-dimensional (2D) radiation distribution imaging. Three cylindrical FODs and three standards TLD_100 for each rat were tested. The measurements of peak irradiation before and after exposure reveal greater stability and superior sensitivity when compared to standard thermo-luminescence detectors in an in-vivo animal test. To the best of our knowledge, FOD testing on live animals is presented for the first time in this paper. Regarding the safety and biocompatibility of FOD, no morphological signs with any kind of inflammation or sensitivity toward the FOD material have been remarked. Moreover, with the current FOD, there is no oedema between the epidermal, dermal, and subdermal sections at the site of implantation. The results also show the stable levels of white blood cells (lymphocytes, granulocytes, MID) as blood inflammatory markers before surgery and at the time of extraction of the implanted dosimeters, thus confirming the biocompatibility for each optical fiber cylinder dosimeter. As a result, the new dosimeters have excellent biocompatibility in living tissues and have 100% accurate reusability intensity of the delivered radiation doses compared to TLD_100 which demonstrated a 45% reduction in its intensity accuracy.

Integrating Network Pharmacology and Molecular Docking Approach to Elucidate the Mechanism of Commiphora wightii for the Treatment of Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is considered a notable prolonged inflammatory condition with no proper cure. Synovial inflammation and synovial pannus are crucial in the onset of RA. The "tumor-like" invading proliferation of new arteries is a keynote of RA. Commiphora wightii (C wightii) is a perennial, deciduous, and trifoliate plant used in several areas of southeast Asia to cure numerous ailments, including arthritis, diabetes, obesity, and asthma. Several in vitro investigations have indicated C wightii's therapeutic efficacy in the treatment of arthritis. However, the precise molecular action is yet unknown. Material and methods: In this study, a network pharmacology approach was applied to uncover potential targets, active therapeutic ingredients and signaling pathways in C wightii for the treatment of arthritis. In the groundwork of this research, we examined the active constituent-compound-target-pathway network and evaluated that (Guggulsterol-V, Myrrhahnone B, and Campesterol) decisively donated to the development of arthritis by affecting tumor necrosis factor (TNF), PIK3CA, and MAPK3 genes. Later on, docking was employed to confirm the active components' efficiency against the potential targets. Results: According to molecular-docking research, several potential targets of RA bind tightly with the corresponding key active ingredient of C wightii. With the aid of network pharmacology techniques, we conclude that the signaling pathways and biological processes involved in C wightii had an impact on the prevention of arthritis. The outcomes of molecular docking also serve as strong recommendations for future research. In the context of this study, network pharmacology combined with molecular docking analysis showed that C wightii acted on arthritis-related signaling pathways to exhibit a promising preventive impact on arthritis. Conclusion: These results serve as the basis for grasping the mechanism of the antiarthritis activity of C wightii. However, further in vivo/in vitro study is needed to verify the reliability of these targets for the treatment of arthritis.

A Fiber-Optical Dosimetry Sensor for Gamma-Ray Irradiation Measurement in Biological Applications.

In this paper, we propose a novel fiber-optical dosimetry sensor for radiation measurement in biological applications. A two-dimensional (2D) fiber-optical dosimeter (FOD) for radiation measurement is considered. The sensors are arranged as a 2D array in a tailored holder. This FOD targets accurate industrial and medical applications which seek more tolerant radiation dosimeters. In this paper, the FOD sensors are subjected to gamma-ray radiation facilities from the 137Cs gamma-ray irradiator type for low doses and 60Co gamma-ray irradiator for high doses. For better evaluation of radiation effects on the FOD sample, the measurements are performed using eight sensors (hollow cylinder shape) with two samples in each dose. The sensors were measured before and after each irradiation. To the author's knowledge, the measurements of FOD transplanted inside animals are presented for the first time in this paper. A 2D simulation program has been implemented for numerical simulation based on the attenuation factors from the absorbed dose inside the in vivo models. A comparison between the FOD and the standard thermo-luminescence detector is presented based on the test of in vivo animal models. The results indicate that the proposed FOD sensor is more stable and has higher sensitivity.

Amygdalin-folic acid-nanoparticles inhibit the proliferation of breast cancer and enhance the effect of radiotherapy through the modulation of tumor-promoting factors/ immunosuppressive modulators in vitro.

INTRODUCTION: Breast cancer (BC) cells often develop multiple mechanisms of chemo- and radio-resistance during tumor progression, which is the major reason for the failure of breast cancer therapy. Targeted nanomedicines have tremendous therapeutic potential in BC treatment over their free drug counterparts. Searching for chemo- and radio-sensitizers to overcome such resistance is therefore urgently required. The goal of this study is to evaluate and compare the radio-sensitizer efficacy of amygdalin-folic acid nanoparticles (Amy-F) on MCF-7 and MDA-MB-231 cells. MATERIALS AND METHODS: The effects of Amy-F on MCF-7 and MDA-MB-231 cell proliferation and IC50 were assessed using MTT assay. The expression of proteins involved in several mechanisms induced by Amy-F in MCF-7 and MDA-MB-231 cells, including growth inhibition, apoptosis, tumor growth regulators, immuno-modulators, and radio-sensitizing activities were evaluated via flow cytometry and ELISA assay. RESULTS: Nanoparticles demonstrated sustained Amy-F release properties and apparent selectivity towards BC cells. Cell-based assays revealed that Amy-F markedly suppresses cancer cell growth and improves radiotherapy (RT) through inducing cell cycle arrest (G1 and sub-G1), and increases apoptosis as well as reduces the proliferation of BC by down-regulating mitogen-activated protein kinases (MAPK/P38), iron level (Fe), nitric oxide (NO), and up-regulating the reactive oxygen species level (ROS). Amy-F has also been shown to suppress the expression of the cluster of differentiation (CD4 and CD80), and interfere with the Transforming growth factor beta (TGF- ß)/Interferon-gamma (INF-g)/Interleukin-2 (IL-2)/Interleukin-6 (IL-6)/Vascular endothelial growth factor (VEGF) induced suppression in its signaling hub, while up-regulating natural killer group 2D receptor (NKG2D) and CD8 expression. CONCLUSIONS: Collectively, the novel Amy-F either alone or in combination with RT abrogated BC proliferation.

Synergistic Effect of Quercetin Magnetite Nanoparticles and Targeted Radiotherapy in Treatment of Breast Cancer.

Quercetin is a potent cancer therapeutic agent present in fruits and vegetables. The pharmaceutical uses of quercetin are limited due to many problems associated with low solubility, bioavailability, permeability, and instability. In addition, the high doses of quercetin show toxic effects in clinical and experimental studies. Therefore, a new strategy is warranted to overcome these problems without the use of toxic doses. The iron oxide nanoparticles can be used as a drug delivery system. This study aimed to prepare quercetin-conjugated magnetite nanoparticles (QMNPs) using biological simple nanoprecipitation and mediated by fungus Aspergillus oryzae. Also, we initiated in vitro and in vivo studies to determine whether QMNPs might sensitize breast cancer to radiotherapy treatment. The structural, morphological, and magnetic properties of the prepared nanoparticles were studied. The results indicated that QMNPs were spherical in shape and 40 nm in diameter. The in vitro studies showed that the incubation of MCF-7, HePG-2, and A459 cancer cells with QMNPs for 24 h effectively inhibited the growth of cancer cell lines in a concentration-dependent manner with IC50 values of 11, 77.5, and104 nmol/mL, respectively. The combination of QMNPs with irradiation (IR) potently blocked MCF-7 cancer cell proliferation and showed significant changes in the morphology of these cells as observed by bright-field inverted light microscopy. Focusing on the long-term toxicity of QMNPs (20 ml/kg), the assessment of hematological, hepatic, and renal markers indicated no toxic effect. Besides, QMNPs inhibited tumor growth and potently enhanced the lateral radiotherapy treatment in N-methyl-N-nitrosourea (MNU)-induced breast cancer in female white albino rats. These anticancer and radiosensitizing activities were ascribed to cytotoxicity, cell cycle arrest, immunomodulation, and efficiency through induction of apoptosis. In a conclusion, these observations suggest that the QMNPs combined with LRT could act as a potential targeted therapy in breast cancer.

Nanoparticles for active combination radio mitigating agents of zinc coumarate and zinc caffeinate in a rat model.

Zinc coumarate and zinc caffeinate nanoparticles (ZnCoNPs, ZnCaNPs) affect different biological processes. This study aimed to evaluate the mitigating action of ZnCoNPs in combination with ZnCaNPs against liver damage induced by gamma rays (γ-rays). Rats were exposed to 7 Gy of γ-rays and then injected intraperitoneally (i.p) with ZnCoNPs [2U/rat/day (5 mg/kg)] and ZnCaNPs [2U/rat/day (15 mg/kg)] for 7 consecutive days. The results showed that irradiated rats treated with ZnCoNPs (5 mg/kg/body weight) in combination with ZnCaNPs (15 mg/kg/body weight) for 7 days had a significant increases in body weight, antioxidant levels, T helper cell 4 (cluster of differentiation 4 (CD4)), and T cytotoxic cell 8 (cluster of differentiation 8 (CD8)), associated with a marked decrease in lipid peroxidation (LP), nitric oxide(NOx), total free radicals concentrate (TFRC), and DNA fragmentation. There were positive alterations in the morphological state, hematological parameters and the cell cycle phases. Additionally, the histopathological study demonstrated an improvement in the liver tissue of irradiated rats after treatment. Thus, ZnCoNPs and ZnCaNPs could be used as natural mitigating agents to reduce the hazards of ionizing radiation.

Dual Hyaluronic Acid and Folic Acid Targeting pH-Sensitive Multifunctional 2DG@DCA@MgO-Nano-Core-Shell-Radiosensitizer for Breast Cancer Therapy.

Globally, breast cancer (BC) poses a serious public health risk. The disease exhibits a complex heterogeneous etiology and is associated with a glycolytic and oxidative phosphorylation (OXPHOS) metabolic reprogramming phenotype, which fuels proliferation and progression. Due to the late manifestation of symptoms, rigorous treatment regimens are required following diagnosis. Existing treatments are limited by a lack of specificity, systemic toxicity, temporary remission, and radio-resistance in BC. In this study, we have developed CD44 and folate receptor-targeting multi-functional dual drug-loaded nanoparticles. This composed of hyaluronic acid (HA) and folic acid (FA) conjugated to a 2-deoxy glucose (2DG) shell linked to a layer of dichloroacetate (DCA) and a magnesium oxide (MgO) core (2DG@DCA@MgO; DDM) to enhance the localized chemo-radiotherapy for effective BC treatment. The physicochemical properties of nanoparticles including stability, selectivity, responsive release to pH, cellular uptake, and anticancer efficacy were thoroughly examined. Mechanistically, we identified multiple component signaling pathways as important regulators of BC metabolism and mediators for the inhibitory effects elicited by DDM. Nanoparticles exhibited sustained DDM release properties in a bio-relevant media, which was responsive to the acidic pH enabling eligibility to the control of drug release from nanoparticles. DDM-loaded and HA-FA-functionalized nanoparticles exhibited increased selectivity and uptake by BC cells. Cell-based assays revealed that the functionalized DDM significantly suppressed cancer cell growth and improved radiotherapy (RT) through inducing cell cycle arrest, enhancing apoptosis, and modulating glycolytic and OXPHOS pathways. By highlighting DDM mechanisms as an antitumor and radio-sensitizing reagent, our data suggest that glycolytic and OXPHOS pathway modulation occurs via the PI3K/AKT/mTOR/NF-κB/VEGFlow and P53high signaling pathway. In conclusion, the multi-functionalized DDM opposed tumor-associated metabolic reprogramming via multiple signaling pathways in BC cells as a promising targeted metabolic approach.

Breast cancer suppression by curcumin-naringenin-magnetic-nano-particles: In vitro and in vivo studies.

BACKGROUND: The limitations of surgery, radiotherapy, and chemotherapy in cancer treatment and the increase in the application of nanomaterials in the field of biomedicine have promoted the use of nanomaterials in combination with radiotherapy for cancer treatment. OBJECTIVE: To improve the efficiency of cancer treatment, curcumin-naringenin loaded dextran-coated magnetic nanoparticles (CUR-NAR-D-MNPs) were used as chemotherapy and in combination with radiotherapy to verify their effectiveness in treating tumors. METHODS: CUR-NAR-D-MNPs were prepared and studied by several characterization methods. Median inhibitory concentration (IC50) and cellular toxicity were evaluated by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. The cell death and radiosensitization were studied by acridine orange/ethidium bromide dual staining of MCF-7 human breast cancer cells. RESULTS: CUR-NAR-D-MNPs induce apoptosis and inhibited cell proliferation through reactive oxygen species (ROS) generation. CUR-NAR-D-MNPs used alone had a certain therapeutic effect on tumors. CUR-NAR-D-MNPs plus radiotherapy significantly reduced the tumor volume and led to cell cycle arrest and induction of apoptosis through modulation of P53high, P21high, TNF-αlow, CD44low, and ROShigh signalingCONCLUSIONS:CUR-NAR-D-MNPs are effective in the treatment of tumors when combined with radiotherapy, and show radiosensitization effects against cancer proliferation in vitro and in vivo.

Total RNA nonlinear polarization: towards facile early diagnosis of breast cancer.

Different cancers are caused by accumulation of numerous genetic and epigenetic changes. Recently, nonlinear polarization has been considered as a marvelous tool for several medical applications. The capability of nonlinear polarization, to monitor any changes in RNA's spectral signature due to breast cancer (BC) was evaluated. Blood samples, from healthy controls and BC patients, were collected for whole blood preparation for genomic total RNA purification. Total RNA samples were stimulated with a light-emitting diode (LED) source of 565 nm; the resonance frequency of investigated RNA samples was captured and processed via hyperspectral imaging. Resonance frequency signatures were processed using fast Fourier transform in an attempt to differentiate between RNA (control) and RNA (BC) via frequency response. RNA (BC) demonstrated a characteristic signal at 0.02 GHz, as well as a phase shift at 0.031, and 0.070 GHZ from RNA (control). These features could offer early BC diagnosis. This is the first time to describe an optical methodology based on nonlinear polarization as a facile principle to distinguish and identify RNA alterations in BC by their characteristic fingerprint spectral signature.

Anticancer and Apoptogenic Effect of Graviola and Low-Dose Radiation in Tumor Xenograft in Mice.

Background:Annona muricata (graviola) has been claimed for its potential against various diseases including cancer. Objective: The present study aimed to investigate the anticancer effect of graviola extract on Ehrlich solid tumor (EST) mice along with or without a low dose of γ radiation (LDR). Methods: Mice were treated with graviola 50 mg/kg body weight orally for 30 days after EST induction and exposed to γ-ray (2 Gy/week for 3 weeks). Cell cycle, CD44, TGF-ß, Bcl-2, and annexin V were determined in tumor tissue. Results: The result obtained showed a significant decrease (P < .05) of tumor size in 28 graviola-treated EST-bearing mice group (EG) or graviola-treated and irradiated EST-30-bearing mice (EGR) groups versus the EST group. The large number of cells in the sub-G0/G1 population and low cell number at S and M phases signify tumor cell apoptosis and inhibition of cell division in EG or EGR groups. Additionally, significant increases in the expression of CD44 and TGF-ß were recorded in EST mice as compared with EG or EGR mice. Furthermore, EST mice exhibited a decrease in the apoptotic marker annexin v and increase in antiapoptotic Bcl-2 compared with EG and EGR mice. Conclusion: It could be suggested that graviola exerts its antitumor effect throughout the regulation of the tumor cell cycle as well as inducing apoptotic signals. The combined treatment of graviola and LDR augments their effect on tumor proliferation.