Targeting the NF-κB p65/Bcl-2 signaling pathway in hepatic cellular carcinoma using radiation assisted synthesis of zinc nanoparticles coated with naturally isolated gallic acid.

PURPOSE: Oral diethylnitrosamine (DEN) is a known hepatocarcinogen that damages the liver and causes cancer. DEN damages the liver through reactive oxygen species-mediated inflammation and biological process regulation. MATERIALS AND METHODS: Gallic acid-coated zinc oxide nanoparticles (Zn-GANPs) were made from zinc oxide (ZnO) synthesized by irradiation dose of 50 kGy utilizing a Co-60 γ-ray source chamber with a dose rate of 0.83 kGy/h and gallic acid from pomegranate peel. UV-visible (UV) spectrophotometry verified Zn-GANP synthesis. TEM, DLS, and FTIR were utilized to investigate ZnO-NPs' characteristics. Rats were orally exposed to DEN for 8 weeks at 20 mg/kg five times per week, followed by intraperitoneal injection of Zn-GANPs at 20 mg/kg for 5 weeks. Using oxidative stress, anti-inflammatory, liver function, histologic, apoptotic, and cell cycle parameters for evaluating Zn-GANPs treatment. RESULTS: DEN exposure elevated inflammatory markers (AFP and NF-κB p65), transaminases (AST, ALT), γ-GT, globulin, and total bilirubin, with reduced protein and albumin levels. It also increased MDA levels, oxidative liver cell damage, and Bcl-2, while decreasing caspase-3 and antioxidants like GSH, and CAT. Zn-GANPs significantly mitigated these effects and lowered lipid peroxidation, AST, ALT, and γ-GT levels, significantly increased CAT and GSH levels (p<0.05). Zn-GANPs caused S and G2/M cell cycle arrest and G0/G1 apoptosis. These results were associated with higher caspase-3 levels and lower Bcl-2 and TGF-ß1 levels. Zn-GANPs enhance and restore the histology and ultrastructure of the liver in DEN-induced rats. CONCLUSION: The data imply that Zn-GANPs may prevent and treat DEN-induced liver damage and carcinogenesis.

Assessment of the effect of drying on Brassica greens via a multiplex approach based on LC-QTOF-MS/MS, molecular networking, and chemometrics along with their antioxidant and anticancer activities.

Turnip (Brassica rapa var rapa L.) leaves are a rich source of versatile bioactive phytochemicals with great potential in the food and herbal industries. However, the effect of drying on its constituents has never been studied before. Hereto, three drying techniques were compared, namely, lyophilization (LY), vacuum oven (VO), and shade drying (SD). Chemical profiling utilizing liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS) combined with chemometrics showed the different impacts of the drying methods on the phytochemical composition of the alcoholic leaf extracts. Unsupervised principal component analysis (PCA) and supervised partial least squares-discriminant analysis (PLS-DA) of the LC-QTOF-MS/MS data showed distinct distant clustering across the three drying techniques. Loading plots and VIP scores demonstrated that sinapic acid, isorhamnetin glycosides, and sinapoyl malate were key markers for LY samples. Meanwhile, oxygenated and polyunsaturated fatty acids were characteristic for SD samples and oxygenated polyunsaturated fatty acids and verbascoside were characteristic for VO samples. LY resulted in the highest total phenolics (TP) and total flavonoid (TF) contents followed by SD and VO. LY and SD samples had much higher antioxidant activity than VO measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH), oxygen radical absorbance capacity (ORAC), and iron metal chelation assays. According to the anticancer activity, the drying methods were ranked in descending order as SD > LY â‰« VO when tested against colon, breast, liver, and lung cancer cell lines. Among the identified compounds, flavonoids and omega-3 fatty acids were key metabolites responsible for the anticancer activity as revealed by partial least squares (PLS) regression and correlation analyses. In conclusion, compared to LY, SD projected out as a cost-effective drying method without compromising the phytochemical and biological activities of Brassica greens. The current findings lay the foundation for further studies concerned with the valorization of Brassica greens.

Regulating microsomal triglyceride transfer protein with natural products for the treatment of hyperlipidaemia.

Hyperlipidaemia, characterised by elevated levels of lipids, particularly LDL-C, is a significant risk factor for atherosclerotic cardiovascular disease. While synthetic inhibitors of microsomal triglyceride transfer protein (MTP) have shown potential in lowering LDL-C, they are associated with adverse effects. This study explores a novel approach by screening natural products to identify plant extracts that down-regulate MTP gene expression, aiming to reduce hyperlipidaemia with fewer side effects. Modulating MTP expression, rather than direct inhibition, offers a promising avenue for lowering plasma lipids and mitigating cardiovascular risk. Various plant extracts were examined for their potential as MTP down-regulators, with Liquorice root and Pomegranate rind extracts demonstrating the highest efficacy. Additionally, the study assessed the total phenolic content of these extracts, revealing their -antioxidant capacity. This research provides a foundation for further investigation into bioactive molecules as potential anti-hyperlipidemic agents with improved safety profiles, addressing a critical need in cardiovascular disease prevention.

Chrysin Encapsulated Copper Nanoparticles with Low Dose of Gamma Radiation Elicit Tumor Cell Death Through p38 MAPK/NF-κB Pathways.

Improving radiation effect on tumor cells using radiosensitizers is gaining traction for improving chemoradiotherapy. This study aimed to evaluate copper nanoparticles (CuNPs) synthesized using chrysin as radiosensitizer with γ-radiation on biochemical and histopathological approaches in mice bearing Ehrlich solid tumor. CuNPs were characterized with irregular round sharp shape with size range of 21.19-70.79 nm and plasmon absorption at 273 nm. In vitro study on MCF-7 cells detected cytotoxic effect of CuNPs with IC50 of 57.2 ± 3.1 µg. In vivo study was performed on mice transplanted with Ehrlich solid tumor (EC). Mice were injected with CuNPs (0.67 mg/kg body weight) and/or exposed to low dose of gamma radiation (0.5 Gy). EC mice exposed to combined treatment of CuNPs and radiation showed a marked reduction in tumor volume, ALT and CAT, creatinine, calcium, and GSH, along with elevation in MDA, caspase-3 in parallel with inhibition of NF-κB, p38 MAPK, and cyclin D1 gene expression. Comparing histopathological findings of treatment groups ends that combined treatment was of higher efficacy, showing tumor tissue regression and increase in apoptotic cells. In conclusion, CuNPs with a low dose of gamma radiation showed more powerful ability for tumor suppression via promoting oxidative state, stimulating apoptosis, and inhibiting proliferation pathway through p38MAPK/NF-κB and cyclinD1.

Boswellic acid coated zinc nanoparticles attenuate NF-κB-mediated inflammation in DSS-induced ulcerative colitis in rats.

INTRODUCTION: Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease, and until now therapeutic agents for UC still cannot exert satisfied effects. Therefore, this study aimed to investigate the ameliorative effect of boswellic acid coated zinc nanoparticles (BAs-ZnNPs) on dextran sodium sulphate (DSS) induced-UC in rats. METHODS: Rats were divided into five groups; control, BAs-ZnNPs, DSS, DSS+BAs, and DSS + BAs-ZnNPs. The activity of alkaline phosphatase (ALP) was determined colorimetrically, while the concentration of IgM, IgG, TNF-α, IL-1ß, and IL-8 were measured by ELISA. Levels of gene expression of NF-κB and COX-2 genes were evaluated by RT-qPCR, while the expression of protein levels of PI3K and STAT-3 were done by western blotting. Finally, histopathological examination of colon tissues of different groups of rats was done. RESULTS: The depicted ball-like structure of the BAs-ZnNPs in the TEM images ranging in size from 50 to 100 nm in diameter while their formation was confirmed by UV-visible spectroscopy with a sharp peak of maximum absorbance at 266 nm. Our results revealed that BAs-ZnNPs exerted an anti-inflammatory effect in the experimental model of colitis, demonstrated histologically and biochemically as shown by the improvement of ALP, IgM, IgG, and the gene expression levels of NF-κB and COX-2. Also, this beneficial effect was associated with the reduction in the expression of TNF-α, IL-1ß, IL-8, PI3K, and STAT-3. Thus, this effect improves the altered immune response associated with the colonic inflammation. CONCLUSION: BAs-ZnNPs can be proposed as a therapeutic candidate to attenuate UC. The potential underlying mechanism includes suppression of ALP, IgM, IgG, IL-1ß, and IL-8 levels via regulation of NF-κB and COX-2 gene expression and STAT-3 and PI3K protein expression in a UC rat model.

Chitosan-Encapsulated Nano-selenium Targeting TCF7L2, PPARγ, and CAPN10 Genes in Diabetic Rats.

This study investigates the antidiabetic and antioxidant potential of chitosan-encapsulated selenium nanoparticles in streptozotocin-induced diabetic model. Glibenclamide was used as a reference antidiabetic drug. Forty-eight adult male Wistar rats were used along the study and divided equally into 6 groups of (I) normal control, (II) chitosan-encapsulated selenium nanoparticles (CTS-SeNPs), (III) glibenclamide, (IV) streptozotocin (STZ), (V) STZ + CTS-SeNPs, and (VI) STZ + Glib. The animals were sacrificed on the 35th day of the experiment. Serum glucose, insulin, IGF-1, ALT, AST, CK-MB, oxidative stress, lipid profile, and inflammatory parameters were subsequently assessed. Also, the expression level of TCF7L2, CAPN10, and PPAR-γ genes were evaluated using qPCR. In addition, histopathological studies on pancreatic tissue were carried out. The results revealed that STZ induced both diabetes and oxidative stress in normal rats, manifested by the significant changes in the studied parameters and in the physical structure of pancreatic tissue. Oral administration of CTS-SeNPs or Glib results in a significant amelioration of the levels of serum fasting blood glucose, insulin, IGF-1, AST, ATL, and CK-MB as compared with STZ-induced diabetic rats. CTS-SeNPs and Glib diminished the level of lipid peroxidation, increased total antioxidant capacity level, as well as possessed strong inhibition against serum α-amylase and α-glucosidase activities. Diabetic animals received CTS-SeNPs, or Glib demonstrated a significant (p < 0.05) decrease in the expression level of TCF7L2 and CAPN10 genes with a significant increase in the expression level of PPAR-γ gene, compared to STZ group. The above findings clarify the promising antidiabetic and antioxidant effect of CTS-SeNPs, recommending its inclusion in the currently used protocols for the treatment of diabetes and in the prevention of its related complications.

Mesenchymal Stem Cells and Selenium Nanoparticles Synergize with Low Dose of Gamma Radiation to Suppress Mammary Gland Carcinogenesis via Regulation of Tumor Microenvironment.

Breast cancer is one of the most prevalent and deadliest cancers among women in the world because of its aggressive behavior and inadequate response to conventional therapies. Mesenchymal stem cells (MSCs) combined with green nanomaterials could be an efficient tool in cell cancer therapy. This study examined the curative effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) with selenium nanoparticles (SeNPs) coated with fermented soymilk and a low dose of gamma radiation (LDR) in DMBA-induced mammary gland carcinoma in female rats. DMBA-induced mammary gland carcinoma as marked by an elevation of mRNA level of cancer promoter genes (Serpin and MIF, LOX-1, and COL1A1) and serum level of VEGF, TNF-α, TGF-ß, CA15-3, and caspase-3 with the reduction in mRNA level of suppressor gene (FST and ADRP). These deleterious effects were hampered after treatment with BM-MSCs (1 × 106 cells/rat) once and daily administration of SeNPs (20 mg/kg body weight) and exposure once to (0.25 Gy) LDR. Finally, MSCs, SeNPs, and LDR notably modulated the expression of multiple tumor promoters and suppressor genes playing a role in breast cancer induction and suppression.

In-vivo and in-silico studies of Eucalyptus kino polyphenolics: outstanding activity in quenching solid liver tumors through inhibition of MMP-9 and TGF-ß gene expression.

As a result of our continuous research efforts to investigate the molecular mechanisms of Eucalyptus kino polyphenolics for healing liver solid tumors, in-vivo histopathological studies of the solid tumor tissues and in-silico molecular docking were carried out. Histopathology of female mice treated with a dose of 200 mg/kg Eucalyptus kino methanolic extract in combination with low level ionising γ-radiation (0.25 Gy) recovered a near-to-normal histological structure revealing a substantial number of cells with hyper-chromachia in nuclei, fibroblast lobules and necrotic cells. Analysis for matrix metalloproteinase-9 (MMP-9) by Western blot and also molecular docking study were conducted to evaluate and rank the potential of the individual components dominated in the extract to inhibit MMP-9 and TGF-ß. The current study presents new lead compounds for the design of novel MMP-9 and TGF-ß strong inhibitors of natural origin.

Rationale for Tailoring an Alternative Oncology Trial Using a Novel Gallium-Based Nanocomplex: Mechanistic Insights and Preclinical Challenges.

Introduction: In the fight against cancer, cisplatin is most widely used as a clinical mainstay for the chemotherapy of various human cancers. Meanwhile, its cytotoxic profile, as well as drug resistance, limits its widespread application. The goal of precision medicine is to tailor an optimized therapeutic program based on the biology of the disease. Recently, nanotechnology has been demonstrated to be promising in this scenario. Objective: The current work provides a rationale for the design of an alternative oncology trial for the treatment of hepatocarcinogenesis using a novel eco-friendly nanocomplex, namely gallic acid-coated gallium nanoparticles. Moreover, the study tests whether the antineoplastic efficacy of gallic acid-coated gallium nanoparticles could be enhanced or not when it is administrated together with cisplatin. Methods: The work comprised a series of both in vitro and in vivo investigations. The in vivo therapeutic efficacy of such treatments, against diethylnitrosamine-induced hepatocarcinogenesis, was strictly evaluated by tracking target genes expressions, iron homeostasis, diverse biomarkers alterations, and lastly, routine paraclinical investigations were also assessed. Results: The in vitro biological evaluation of gallic acid-coated gallium nanoparticles in a HepG-2 cancer cell line established its superior cytotoxicity. Else more, the results of the in vivo experiment highlighted that gallic acid-coated gallium nanoparticles could diminish key hallmarks of cancer by ameliorating most of the investigated parameters. This was well-appreciated with the histopathological findings of the liver architectures of the treated groups. Conclusions: Our findings suggest that novel biogenic Ga-based nanocomplexes may potentially present new hope for the development of alternative liver cancer therapeutics, which should attract further scientific interest.

Antitumor and Antibacterial Efficacy of Gallium Nanoparticles Coated by Ellagic Acid.

Cancer is a mortality contributor worldwide, and breast cancer is the most common among women. Despite the numerous breast cancer therapeutic strategies, they either have limitations or sometimes are resisted by cancer, so new approaches are needed to tackle those restrictions. Nanotechnology offers exciting leaps in the diagnosis and treatment of cancer, especially breast cancer. The main objective of this study was to investigate the effect of the newly synthesized gallium nanoparticles coated by Ellagic acid (EA-GaNPs) on the induced mammary gland carcinogenesis in female rats and their antibacterial activities comparison with standard antibiotics (Ketoconazole (100 µg/ml) and Gentamycin (4 µg/ml)) by disc diffusion method using eight different microbial species. The antitumor efficacy of EA-GaNPs was conducted both in vitro and in in vivo. The result of antimicrobial activity of EA-Ga NPs (1 mg/1 mL) revealed moderate toxicity behavior against Gram-positive {Staphylococcus aureus, Bacillus subtilis, Bacillus cereus) and Gram-negative pathogenic bacteria {Escherichia coli, Proteus vulgarfs) also, antifungal activity was detected against {Aspergillus terreus). In vitro study showed that EA-GaNPs inhibited human breast cancer cell line (MCF-7) proliferation with IC50 of 2.86 µg/ml. Although in vivo; the administration of EA-GaNPs to DMBA-treated rats ameliorated the hyperplastic state of mammary gland carcinogenesis induced by DMBA. Additionally, EA-GaNPs administration significantly modulated the activities of ALT and AST, as well as the levels of urea and creatinine in serum. Also, EA-GaNPs administration improved the antioxidant state by increasing Superoxide dismutase activity and GSH content, and decreasing malondialdehyde content in the mammary tissue, besides enhancing the apoptotic activity through elevating the levels of caspase-3 and decreasing the protein intensities of protein kinase B & phosphatidyl inositide 3-kinases. Furthermore, a significant decrease in serum Total iron-binding capacity accompanied by a significant increase in the level of calcium was noted. So, it can be concluded that the newly synthesized nanoparticles EA-GaNPs have an efficient antitumor activity that was manifested by reduction of the viability on the human breast cancer cell line (MCF-7) in vitro. Also, in vivo against the chemically induced mammary gland carcinogenesis in a female rat model. Histopathological findings were in harmony with biochemical and molecular results showing the effectiveness of EA-GaNPs against mammary carcinogenesis. Therefore, EA-GaNPs could be a promising, potent anti-cancer compound.

Lactobacillus acidophilus ATCC 4356 Exopolysaccharides Suppresses Mediators of Inflammation through the Inhibition of TLR2/STAT-3/P38-MAPK Pathway in DEN-Induced Hepatocarcinogenesis in Rats.

Probiotics have been suggested as a safe and cost-effective approach to prevent or treat hepatocellular carcinoma (HCC). Some of the exopolysaccharides (EPSs) produced by lactic acid bacteria confer health benefits such as immunomodulatory and antitumor activities. The present study was therefore aimed to investigate the immunomodulatory effect of Lactobacillus acidophilus ATCC 4356 EPSs against diethylnitrosamine (DEN) and gamma radiation (IR) induced HCC either as prevention or treatment in male rats' model. Biochemical results revealed a significant increase in serum ALT and γ-GT activities as well as MDA, IL-17, TGF-ß1, signal transducer and activator of transcription-3 protein (STAT3), mitogen-activated protein kinase p38 (p38MAPK) levels in the liver tissue. The gene expression level of the liver toll-like receptor 2 (TLR-2) gene was also increased. However, prevention and treatment with EPSs ameliorated most of the investigated parameters. The histopathological observations of liver tissues were in agreement with restored biochemical results. In conclusion, Lactobacillus acidophilus ATCC 4356 EPSs are efficacious control against HCC throughout the regulation of TLR2/STAT-3/P38-MAPK Pathway associated with inflammation. Therefore, our novel EPSs ATCC 4356 could be used as a good, safe and effective probiotic to prevent hepatocarcinogenesis in suspected patients.

Eucalyptus kino: a treasure trove of polyphenols eradicating tumors in-vivo by elevating caspase-3 level, inhibiting TGF-ß and NF-κb gene expression.

30 secondary polyphenolic metabolites were characterised in Eucalyptus kino methanol extract using HPLC-MS/MS. The antitumor activity of the extract in combination with low level ionising radiation in female mice with solid tumors from inoculated Ehrlich ascites carcinoma cells was investigated. Tumor cell-inoculated mice received daily extract doses (100 mg/kg, 200 mg/kgBW) with or without a single exposure to 0.25 Gy γ-rays, and cis-platin as a reference anticancer drug. Changes in the tumor volume, oxidative state, levels of caspase-3, TGF-ß and Nf-κB were assessed by q-PCR. Surprisingly, a dose of 200 mg/kg extract together with γ-radiation remarkably reduced the tumor volume, improved the oxidative and apoptotic biomarker levels. In conclusion, results showed that a combination of kino extract with low level γ-radiation synergistically reduced tumor progression due to the antioxidant and anti-proliferative activities of the polyphenolics in the extract.

Ameliorative potential of manganese nanoparticles with low-level ionizing radiation against experimentally induced hepatocarcinogenesis.

Nanotechnology is a rich field with infinite possibilities of drug designs for cancer treatment. We aimed to biosynthesize manganese nanoparticles (Mn NPs) using Lactobacillus helveticus to investigate its anticancer synergistic effect with low-dose gamma radiation on HCC-induced rats. Diethylnitrosamine (DEN) (20 mg/kg BW, 5 times a week for 6 weeks) induced HCC in rats. Rats received Mn NPs (5 mg/kg BW/day) by gastric gavage over 4 weeks concomitant with single dose of gamma radiation (γ-R) (0.25 Gy). Characterization, cytotoxicity, and anticancer activity of Mn NPs were evaluated. DEN-induced significant liver dysfunction (alanine transaminase activity ALT, total proteins, and albumin levels) associated with significant increase in lipid peroxidation levels with reduction in super oxide dismutase activity. Furthermore, DEN intoxication is sponsored for remarkable increase in levels of Alfa-fetoprotein, tumor necrosis factor α, vascular endothelial growth factor, and transforming growth factor beta with remarkable decrease in caspase 3 and cytochrome c. Treatment with Mn NPs (4.98-11.58 nm) and single dose gamma radiation evoked significant repair in ALT, total protein, and albumin accompanied with balanced oxidative status, diminished inflammatory biomarkers, angiogenic factor, and growth factor with restoration in apoptotic factors. Mn NPs revealed obvious in vitro cytotoxic activity against HepG2 cell line in a dose-dependent manner. Our findings were well appreciated with the histopathological study. In conclusion, a new approach of the single or combined use of Mn NPs with low-dose γ-radiation regimens as promising paradigm for HCC treatment is recommended.

Assessment of combining biosynthesized silver nanoparticles using Bacillus thuringiensis and gamma irradiation for controlling Pectinophora gossypiella (saunders) (lepidoptera: Gelechiidae).

PURPOSE: Combining gamma irradiation and nanotechnology has become one of the most promising new approaches for area-wide (AW) pest management in recent years. The laboratory trials were conducted to determine the combining effects of BT-AgNPs and gamma irradiation for controlling P. gossypiella. Radio-sensitivity of male pupae at different doses of gamma radiation and the effectiveness of biosynthesized silver nanoparticles using Bacillus thuringiensis on larval instar were assayed. Additionally, the ultrastructure changes on the alimentary canal of 4th instar larvae were studied to evaluate the impact of the combined approach at a cellular level. MATERIALS AND METHODS: Laboratory- rearing technique was used for rearing Pectinophora gossypiella. The irradiation process was achieved at Co60 - Gamma Chamber (4000 A). Alanine dosimeters were used for measuring the average absorbed dose and dose mapping. Preparation of Silver nanoparticles (AgNPs) using Bacillus thuringiensis (Bt) and their characterization has been investigated. The treated 4th instar larvae by gamma irradiation or ∕and BT-AgNPs were dissected under the stereo microscope. The alimentary canal was obtained anatomically and Transmission Electron Microscope) was used in examining the stained sections. RESULTS: Based on the nonhatching eggs produced by irradiated males' pupae, the values of effective doses were calculated. The effective doses ranged from 16 to 291 Gy for the ED25 - ED75. The sterility index reached 74.1% when irradiated with males by 291 Gy crossed with nonirradiated females and the adult emergence decreased to be 35.3%. The insecticidal potential of Bt-AgNPs on the 2nd and 4th larval instars was dose-dependent and its LC50 toxicity value was 0. 3 and 0. 4 mg/ml, respectively. The lethal concentration LC50 of the 2nd instar larvae increased the larval and pupal mortality to 55% and 44.4%, respectively, and reduced the adult emergence to be 55.6%. The combining effects of Bt-AgNPs with 291 Gy induced 100% pupae mortality and there was no adult emergence in F1 generation. Such effects also severed the ultrastructure deformity of the midgut of the 4th instar larvae after the two-day post-treatment. CONCLUSIONS: The combining effects are recommended as an effective IPM program to control P. gossypiella by releasing sterile males (derived from pupae irradiated with 291 Gy) crossing with the normal females in the field, and reducing the fertility of the population to 31.2%. Subsequently, the resulted larvae treated with LC50 of Bt-AgNPs prevented the adult emergence and stopped the life cycle of P. gossypiella.

Amphora algae with low-level ionizing radiation exposure ameliorate D-galactosamine-induced inflammatory impairment in rat kidney.

d-Galactosamine (d-GalN) is a well-known toxin that causes many metabolic and morphological abnormalities resulting in advanced renal failure and liver damage. Occupational exposure to low-level ionizing radiation (<1 Gy) was shown to enhance cell protection via attenuating an established inflammatory process. The present study was therefore aimed to investigate the protective impact of Amphora coffaeiformis extract and low dose gamma radiation against d-GalN induced renal damage in rats. Forty-eight adult male Swiss albino rats were distributed equally into eight groups. The measurements included antioxidants activities (superoxide dismutase, catalase and glutathione peroxidase) as well as lipid peroxidation level in kidney tissue. Also, kidney function tests and inflammatory markers (tumor necrosis factor alpha and nuclear factor kappa-light-chain-enhancer of activated B cells) were measured. Additionally, relative quantification of kidney nuclear factor erythroid 2-related factor 2 (Nrf-2) gene was estimated. Histopathological examination was also performed in kidney tissue. The results revealed decreases in antioxidant activities and downregulation of Nrf-2 expression accompanied by increases in lipid peroxidation level, kidney function tests and inflammatory markers in d-GaIN group. The treatment with Amphora algal extract and low dose gamma radiation ameliorated the previous measurements which were harmony with histopathological findings. In conclusion, A coffaeiformis extract and low dose gamma radiation provided marked functional and histological effects in the treating acute renal damage induced by d-GalN in rats.

Phytochemical study, potential cytotoxic and antioxidant activities of selected food byproducts (Pomegranate peel, Rice bran, Rice straw & Mulberry bark).

The aim of the study is to evaluate common food by-products (Pomegranate peel, Rice bran, Rice straw & Mulberry bark) to screen out their medicinal importance such as cytotoxic & antioxidant activities. HPLC revealed that all tested samples were rich in phenolics. Tested samples exerted significant antioxidant activity with high potency to Pomegranate peel. All tested extracts were able to reduce cell viability of tested cell lines in a dose-response manner after treatment. In most cases, the IC50 values were under 30 µg/ml except IC50 of pomegranate peel against breast cell line (42.4 ug/ml). The antioxidant and cytotoxic properties of pomegranate peel, rice bran, rice straw and mulberry bark have been attributed to synergetic effects of phenolic phytochemicals.

Gallium nanoparticles along with low-dose gamma radiation modulate TGF-ß/MMP-9 expression in hepatocellular carcinogenesis in rats.

Combining chemotherapy with radiotherapy potentiates the outcome of cancer treatment for the more comprehensive attack. In the current study, we continued to assess the therapeutic efficaciousness of the newly synthesized gallium nanoparticles (GaNPs) combined with low level of gamma radiation (IR), on the incidence of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats. Oral administration of GaNPs (1 mg/Kg b.wt.) 5 times per week for 6 weeks combined with IR to rats treated with DEN (20 mg/Kg b.wt. 5 times per week for 6 weeks) significantly reduced serum levels of alpha-fetoprotein (AFP), aspartate transferase (AST), alanine transferase (ALT), and gamma-glutamyltransferase (GGT). In addition, the immunoblotting results of matrix metalloproteinase-9 (MM-9) showed a marked downregulation of protein expression along with a significant decrease in the hepatic level of transforming growth factor ß (TGF-ß). Furthermore, GaNPs and/or low dose of radiation significantly elevated the level of caspase-3 gene transcript accompanied with evoked DNA fragmentation in rats treated with DEN. The ameliorative effect of GaNPs and IR well appreciated with the histopathological alteration finding in DEN groups. It can be concluded that the combination of GaNPs and/or IR can serve as a good therapeutic agent for the treatment of HCC, which ought to attract more studies.

Anticancer redox activity of gallium nanoparticles accompanied with low dose of gamma radiation in female mice.

Guided treatments with nanoparticles and radiotherapy are a new approach in cancer therapy. This study evaluated the beneficial antitumor effects of γ-radiation together with gallium nanoparticles against solid Ehrlich carcinoma in female mice. Gallium nanoparticles were biologically synthesized using Lactobacillus helveticus cells. Transmission electron microscopy showed gallium nanoparticles with size range of 8-20 nm. In vitro study of gallium nanoparticles on MCF-7 revealed IC50 of 8.0 µg. Gallium nanoparticles (0.1 mg/kg body weight) were injected intraperitoneally daily on the seventh day of Ehrlich carcinoma cells inoculation. Whole-body γ-radiation was carried out at a single dose of 0.25 Gy on eighth day after tumor inoculation. Biochemical analysis showed that solid Ehrlich carcinoma induced a significant increase in alanine aminotransferase activity and creatinine level in serum, calcium, and iron concentrations in liver tissue compared to normal control. Treatment of Ehrlich carcinoma-bearing mice with gallium nanoparticles and/or low dose of γ-radiation exposure significantly reduced tumor volume, decreased alanine aminotransferase and creatinine levels in serum, increased lipid peroxidation, and decreased glutathione content as well as calcium and iron concentrations in liver and tumor tissues with intense DNA fragmentation accompanied compared to untreated tumor cells. Moreover, mitochondria in the treated groups displayed a significant increase in Na+/K+-ATPase, complexes II and III with significant reduction in CYP450 gene expression, which may indicate a synergistic effect of gallium nanoparticles and/or low dose of γ-radiation combination against Ehrlich carcinoma injury, and this results were well appreciated with the histopathological findings in the tumor tissue. We conclude that combined treatment of gallium nanoparticles and low dose of gamma-radiation resulted in suppressive induction of cytotoxic effects on cancer cells.

Fermentation enhances Ginkgo biloba protective role on gamma-irradiation induced neuroinflammatory gene expression and stress hormones in rat brain.

UNLABELLED: Ionizing radiation has attracted a lot of attention due to its beneficial and possible harmful effects to the human population. The brain displays numerous biochemical and functional alterations after exposure to irradiation, which induces oxidative-stress through generation of reactive oxygen species (ROS). The present study evaluated the neuro-protective role of fermented Ginkgo biloba (FGb) leaf extract, compared to non-fermented G. biloba (Gb) leaf extract against γ-irradiation (6Gy) in the rats' brain. The changes of the Gb phytochemical constituents after fermentation, using Aspergillus niger were evaluated by Gas Chromatography-Mass Spectrometry. The results showed a significant decrease in superoxide dismutase (SOD), glutathione peroxidase (GPx) activities and elevation of the calcium level in the brain cytosolic fraction of γ-irradiated rats. Further, significant increases in the malondialdehyde (MDA), the stress hormones (catecholamines); epinephrine (EN), norepinephrine (NE) and dopamine (DA) levels and the interleukin-1-beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) gene expression relative ratio in parallel with a significant decrease in the glutathione (GSH) content and DNA fragmentation in the brain tissues of the γ-irradiated rats were observed. The pre-treatment with Gb extract significantly amended these biochemical parameters. Meanwhile, the pre-treatment with the FGb showed more improvement, compared to Gb, of these biochemical parameters in the brain of γ-irradiated rats, which could be attributed to the enhancement of its antioxidant activity after fermentation. These findings suggested that fermentation enhances the protective effect of Gb in the brain on the neuroinflammation, release of the stress hormones, apoptosis and oxidative damage induced by γ-irradiation. IN CONCLUSION: fermentation improved the bio-activities of Gb leaf extract and thus enhanced the in-vivo antioxidant, anti-apoptotic and anti-inflammatory activities, leading to amelioration of the stress hormones and Ca level. Accordingly, the fermentation enhances the protective role of Gb against γ-irradiation induced physiological disturbance in the rat's brain.