Modifying rheological properties of psyllium by gamma irradiation enables development of low glycaemic index food with a predicted gastrointestinal tolerance.

Gel forming dietary fibre like psyllium (PS) is effective in slowing down rate of digestion as well as absorption of glucose thereby reducing the postprandial glucose level and hence is used to develop functional foods for diabetic patients. The fortification level is however limited which otherwise elicit unwanted rheological response and poor sensorial quality in final product. In the present study this limitation was overcome by improving the functionality of the fibre by gamma radiation processing of the polysaccharides. We assessed the changes in rheological properties of radiation processed PS (RPPS) at different doses which enabled us to optimise the irradiation dose and levels of fortification of the RPPS in wheat flour for preparation of Indian unleavened bread (chapati). We observed that PS processed at a dose of 25 kGy could be incorporated to a level as high as 14 % in wheat flour yielding a sensorially better product compared to unfortified wheat flour. Further, the most striking effect observed for RPPS fortified chapati was reduction in the release of glucose upon subjecting to simulated gastrointestinal digestion. Finally, clinical and in vitro fermentation studies also confirmed a low GI value and high gastrointestinal tolerance of RPPS fortified chapati.

Repurposing of FDA approved kinase inhibitor bosutinib for mitigation of radiation induced damage via inhibition of JNK pathway.

Radiotherapy is a common modality for cancer treatment. However, it is often associated with normal tissue toxicity in 20-80% of the patients. Radioprotectors can improve the outcome of radiotherapy by selectively protecting normal cells against radiation toxicity. In the present study, compound libraries containing 54 kinase inhibitors and 80 FDA-approved drugs were screened for radioprotection of lymphocytes using high throughput cell analysis. A second-generation FDA-approved kinase inhibitor, bosutinib, was identified as a potential radioprotector for normal cells. The radioprotective efficacy of bosutinib was evinced from a reduction in radiation induced DNA damage, caspase-3 activation, DNA fragmentation and apoptosis. Oral administration of bosutinib protected mice against whole body irradiation (WBI) induced morbidity and mortality. Bosutinib also reduced radiation induced bone-marrow aplasia and hematopoietic damage in mice exposed to 4 Gy and 6 Gy dose of WBI. Mechanistic studies revealed that the radioprotective action of bosutinib involved interaction with cellular thiols and modulation of JNK pathway. The addition of glutathione and N-acetyl cysteine significantly reduced the radioprotective efficacy of bosutinib. Moreover, bosutinib did not protect cancer cells against radiation induced toxicity. On the contrary, bosutinib per se exhibited anticancer activity against human cancer cell lines. The results highlight possible use of bosutinib as a repurposable radioprotective agent for mitigation of radiation toxicity in cancer patients undergoing radiotherapy.

Gamma-irradiation of inulin improves its biological functionality and feasibility as a functional ingredient in synbiotic food.

Inulin, a dietary fibre, is widely used as a prebiotic, sugar replacer, and texture modifier in the food industry. In this study, we have shown that irradiation affects the physicochemical properties of inulin, which in turn improves its biological functionality and feasibility as a functional ingredient in synbiotic foods. The biological functionality of 25 kGy-irradiated inulin (IRI) was assessed in terms of antioxidant capacity, protective action against intracellular ROS, and prebiotic activity. Antioxidant assays revealed that irradiated inulin had improved antioxidant activity, which was even greater than that of fructooligosaccharides. Furthermore, IRI was found to be comparatively more effective in maintaining low intracellular ROS levels. The in vitro fermentation studies showed that IRI had higher bifidogenic efficacy than fructooligosaccharides and unirradiated inulin. A synbiotic low-fat yogurt containing IRI (8.5 %) was prepared. In terms of sensory attributes, the developed product was comparable to a commercially available non-synbiotic and high-fat containing product.

Anti-proliferative effect and underlying mechanism of ethoxy-substituted phylloquinone (vitamin K1 derivative) from Spinacia oleracea leaf and enhancement of its extractability using radiation technology.

In our previous studies, a novel antimutagenic compound, 2-ethoxy-3-(3,7,11,15-tetramethylhexadec-2-ethyl) naphthaquinone-1,4-dione (ethoxy-substituted phylloquinone; ESP) from spinach was characterized and mechanism contributing to its antimutagenicity was deduced. In the current study, anti-proliferative activity of ESP was assessed in lung cancer (A549) cells using MTT [3-(4,5-dimethylthiazole-2yl)-2,5-diphenyl tetrazolium bromide], clonogenic assays and cell cycle analysis. ESP treatment showed selective cytotoxicity against lung cancer cells and no cytotoxicity in normal lung (WI38) cells. Cell cycle analysis revealed that ESP treatment arrests A549 cell population in G2-M phase. In-silico analysis indicated positive drug-likeness features of ESP. Molecular docking showed H-bonding and hydrophobic interactions between ESP and B-DNA dodecamer residues at minor groove. SWATH-MS (Sequential Window Acquisition of All Theoretical Mass Spectra) based proteomic analysis indicated down-regulation of proteins involved in EGFR signaling, NEDDylation and other metabolic pathways and up-regulation of tumor suppressor (STAT1 and NDRG1) proteins. Treatment of spinach powder with gamma radiation (5-20 kGy) from cobalt (Co-60) enhanced the extractability of ESP up to 4.4-fold at the highest dose of 20 kGy. Scanning electron microscopy of spinach powder displayed decrease in smoothness and compactness with increase in radiation dose attributing to its enhanced extractability. Increase in the extractability of ESP with increasing radiation doses as measured by fluorescence intensity and dry weight basis was strongly correlated. Nonetheless, radiation treatment did not affect the functionality of ESP in terms of anti-proliferative and antimutagenic activities. Current findings thus highlight broad spectrum bioactivity of ESP from spinach, its underlying mechanism and applicability of radiation technology in enhancing extractability. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03264-6.

Preclinical Studies and Clinical Prospects of Wharton's Jelly-Derived MSC for Treatment of Acute Radiation Syndrome.

PURPOSE OF REVIEW: Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have received widespread attention from researchers owing to the remarkable benefits offered by these cells over other stem cells. The primitive nature of WJ-MSCs, ease of isolation, differentiation ability, and immuno-modulatory nature make these cells superior to bone marrow MSCs and ideal to treat various human ailments. This review explores ability of WJ-MSCs to mitigate acute radiation syndrome caused by planned or unplanned radiation exposure. RECENT FINDINGS: Recent reports suggest that WJ-MSCs home to damaged tissues in irradiated host and mitigate radiation induced damage to radiosensitive tissues such as hematopoietic and gastrointestinal systems. WJ-MSCs and conditioned media were found to protect mice from radiation induced mortality and also prevent radiation dermatitis. Local irradiation-induced lung toxicity in mice was significantly reduced by CXCR4 over-expressing WJ-MSCs. SUMMARY: Emerging evidences support safety and effectiveness of WJ-MSCs for treatment of acute radiation syndrome and lung injury after planned or accidental exposure. Additionally, conditioned media collected after culturing WJ-MSCs can also be used for mitigation of radiation dermatitis. Clinical translation of these findings would be possible after careful evaluation of resilience, effectiveness, and molecular mechanism of action of xenogeneic WJ-MSCs in non-human primates.

Xenogeneic transplantation of human WJ-MSCs rescues mice from acute radiation syndrome via Nrf-2-dependent regeneration of damaged tissues.

There is an unmet medical need for radiation countermeasures that can be deployed for treatment of exposed individuals during ionizing radiation (IR) accidents or terrorism. Wharton's jelly mesenchymal stem cells (WJ-MSCs) from human umbilical cord have been shown to avoid allorecognition and induce a tissue-regenerating microenvironment, which makes them an attractive candidate for mitigating IR injury. We found that WJ-MSCs protected mice from a lethal dose of IR even when transplanted up to 24 hours after irradiation, and a combination of WJ-MSCs and antibiotic (tetracycline) could further expand the window of protection offered by WJ-MSCs. This combinatorial approach mitigated IR-induced damage to the hematopoietic and gastrointestinal system. WJ-MSCs increased the serum concentration of the cytoprotective cytokines granulocyte colony-stimulating factor (G-CSF) and IL-6 in mice. Knockdown of G-CSF and IL-6 in WJ-MSCs before injection to lethally irradiated mice or transplantation of WJ-MSCs to lethally irradiated Nrf-2 knockout mice significantly nullified the therapeutic protective efficacy. Hence, WJ-MSCs could be a potential cell-based therapy for individuals accidentally exposed to radiation.

Controlling the phase and morphology of amorphous Se nanoparticles: their prolonged stabilization and anticancer efficacy.

Applications of amorphous Se nanoparticles (NPs) are limited due to their meticulous synthetic procedures and rapid phase transformation leading to low stability. A highly facile one-pot green method is being reported, wherein apart from tuning the morphology and the phase of the Se NPs, their stabilization could be prolonged to months as compared to a few minutes-to-days, known hitherto.

Troxerutin, a natural flavonoid binds to DNA minor groove and enhances cancer cell killing in response to radiation.

Troxerutin, a flavonoid best known for its radioprotective and antioxidant properties is of considerable interest of study due to its broad pharmacological activities. The present study on troxerutin highlights its abilities to bind DNA and enhance cancer cell killing in response to radiation. Troxerutin showed strong binding with calf thymus DNA in vitro. Troxerutin-DNA interaction was confirmed by CD spectropolarimetry. The mode of binding of troxerutin to DNA was assessed by competing troxerutin with EtBr or DAPI, known DNA intercalator and a minor groove binder, respectively. DAPI fluorescence was drastically reduced with linear increase in troxerutin concentration suggesting possible binding of troxerutin to DNA minor groove. Further, computational studies of docking of troxerutin molecule on mammalian DNA also indicated possible troxerutin-DNA interaction at minor groove of DNA. Troxerutin was found to mainly localize in the nucleus of prostate cancer cells. It induced cytotoxicity in radioresistant (DU145) and sensitive (PC3) prostate cancer cells. When troxerutin pre-treated DU145 and PC3 cells were exposed to γ-radiation, cytotoxicity as estimated by MTT assay, was found to be further enhanced. In addition, the % subG1 population detected by propidium iodide staining also showed similar response when combined with radiation. A similar trend was observed in terms of ROS generation and DNA damage in DU145 cells when troxerutin and radiation were combined. DNA binding at minor groove by troxerutin may have contributed to strand breaks leading to increased radiation induced cell death.

Troxerutin, a plant flavonoid, protects cells against oxidative stress-induced cell death through radical scavenging mechanism.

Troxerutin (TRX) is a flavonoid present in tea, coffee, cereal grains, various fruits and vegetables have been reported to exhibit radioprotective, antithrombotic, nephro and hepato-protective effects. A systematic study was undertaken to evaluate its free radical scavenging ability and anti-apoptotic activity in cell-free and cellular systems. TRX scavenged superoxide, nitric oxide and also other model stable radicals like 1,1-diphenyl-2-picryl-hydazyl, and 2,2'-azinobis3-ethylbenzothiazoline-6-sulfonic acid. It reacted with hydroxyl radicals, carbonate and thiocyanate anions, as evaluated by pulse radiolysis and stopped flow techniques. TRX protected different cell types (epithelial cells, fibroblasts and lymphocytes) against peroxyl radical-induced apoptosis, necrosis and mitotic death. It scavenged intracellular basal and inducible ROS levels and also restored depletion of intracellular GSH levels, suggesting that free radical scavenging ability may be responsible for the observed cytoprotection of different cell types. TRX may find application as an adjuvant in treating various diseases attributed to oxidative stress.

Fungal beta glucan protects radiation induced DNA damage in human lymphocytes.

BACKGROUND: Ganoderma lucidum (Ling Zhi), a basidiomycete white rot macrofungus has been used extensively for therapeutic use in China, Japan, Korea and other Asian countries for 2,000 years. The present study is an attempt to investigate its DNA protecting property in human lymphocytes. MATERIALS AND METHODS: Beta glucan (BG) was isolated by standard procedure and the structure and composition were studied by infrared radiation (IR) and nuclear magnetic resonance (NMR) spectroscopy, gel filtration chromatography and paper chromatography. The radioprotective properties of BG isolated from the macro fungi Ganoderma lucidum was assessed by single cell gel electrophoresis (comet assay). Human lymphocytes were exposed to 0, 1, 2 and 4 Gy gamma radiation in the presence and absence of BG. RESULTS: The comet parameters were reduced by BG. The results indicate that the BG of G. lucidum possessed significant radioprotective activity with DNA repairing ability and antioxidant activity as the suggestive mechanism. CONCLUSIONS: The findings suggest the potential use of this mushroom for the prevention of radiation induced cellular damages.

Anticancer property of gallic acid in A549, a human lung adenocarcinoma cell line, and possible mechanisms.

Gallic acid is widely distributed in plants, fruits and foods with a range of biological activities. In the present study the possible mechanisms of gallic acid anticancer properties were explored in A549, a human lung adenocarcinoma cell line. Our study shows that it inhibited the A549 cell growth and decreased cell viability monitored at 24 h. It also inhibited cell proliferation in dose- and time-dependent manner as measured by 3-[4,5-methylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide assay at 24 and 48 h. Morphological examination of the cells after gallic acid treatment showed the typical feature of cell death such as cell shrinkage and rounding up of the cells. Clonogenic assay indicated that gallic acid treatments inhibited the colony formation. DNA fragmentation assay indicated the disappearance of the genomic DNA in dose-dependent manner. To find out possible mechanisms, mitochondrial potential and intracellular reactive oxygen species were measured. It was observed that gallic acid treatment decreased mitochondrial membrane potential and increased intracellular reactive oxygen species. Further caspases activity was measured and it was found that gallic acid activated the caspase-3 but not caspase-8 indicating the involvement of intrinsic pathway of cell apoptosis.

Therapy with un-engineered naïve rat umbilical cord matrix stem cells markedly inhibits growth of murine lung adenocarcinoma.

BACKGROUND: Lung cancer remains the leading cause of cancer-related mortality despite continuous efforts to find effective treatments. Data from the American Cancer Society indicate that while the overall incidence of lung cancer is declining, it continues to rise in women. Stem cell-based therapy has been an emerging strategy to treat various diseases. The purpose of this paper is to determine the efficacy of an intrinsic anti-cancer effect of rat umbilical cord matrix stem cells (UCMSCs) on lung cancer. METHODS: A mouse syngeneic lung carcinoma model was used to test the basic ability of UCMSCs to control the growth of lung cancer. Lung tumors were experimentally induced by tail vein administration of Lewis lung carcinoma (LLC) cells derived from the lung of C57BL/6 mouse. Rat UCMSCs were then administered intratracheally five days later or intravenously on days 5 and 7. The tumor burdens were determined by measuring lung weight three weeks after the treatment. RESULTS: Co-culture of rat UCMSCs with LLC significantly attenuated the proliferation of LLC cells as monitored by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), a tetrazole cell proliferation assay, thymidine uptake, and direct cell counts. In vitro colony assays with rat UCMSCs as feeder layers markedly reduced LLC colony size and number. Co-culture of rat UCMSCs with LLCs causes G0/G1 arrest of cancer cells. This is evident in the decrease of cyclin A and CDK2 expression. The in vivo studies showed that rat UCMSC treatment significantly decreased tumor weight and the total tumor mass. Histological study revealed that intratracheally or systemically administered rat UCMSCs homed to tumor areas and survived for at least 3 weeks without any evidence of differentiation or adverse effects. CONCLUSIONS: These results indicate that rat UCMSCs alone remarkably attenuate the growth of lung carcinoma cells in vitro and in a mouse syngeneic lung carcinoma graft model and could be used for targeted cytotherapy for lung cancer.

Some novel approaches for radioprotection and the beneficial effect of natural products.

Due to the increased use of ionizing radiation in various aspects of human life especially in areas pertaining to radiotherapy of cancer, food preservation, agriculture, industry and power generation, there is a need to develop an effective and non-toxic radioprotector. The currently available ones have many drawbacks including high cost, side effects and toxicity. Several novel approaches are on to locate a potent radioprotector. These include mimics of antioxidant enzymes, nitroxides, melatonin, growth factors, gene therapy, hyperthermia apart from natural products. The latter has several advantages since they are non-toxic with proven therapeutic benefits. These can be classified as natural compounds and plant extracts; polyherbal formulations; besides natural and semi-natural compounds of plant origin. A review of the above agents, their efficacy in radioprotection and possible mechanisms responsible has been carried out. As India and many Eastern countries have an enormous heritage of vast natural dietary and time tested medicinal resources it is worth exploring the possibility of developing efficient, economically viable and clinically acceptable radioprotectors for human application from these resources.