Disruption of the redox balance with either oxidative or anti-oxidative overloading as a promising target for cancer therapy

Abstract Oxidative stress acts as a double edged sword by being both a promoter and a suppressor of cancer. Moderate oxidative stress is beneficial for cancer cell proliferative and invasiveness features, while overexposure of the cells to oxidative insults could induce cancer cell apoptosis and reduce hypoxia along with modulating the immune system for regression of tumor. Cancer cells and cancer stem cells have highly efficient redox systems that make them resistant to oxidative insults. The redox disruptive approach is an area of current research and key for oxidative targeted cancer therapies. This disruption is applicable by using either oxidative or anti oxidative overloading strategies, specifically on cancer cells without influencing normal cells or tissues around tumor. The activity of tumor suppressor cells within tumor microenvironment is needed to be maintained in patients receiving such approaches. KEYWORDS: cancer, oxidative stress, reactive oxygen species (ROS), redo

Comparison of the effects of progesterone and 17 β-estradiol on Schwann cell markers expression in rat adipose-derived stem cells

Steroids promote the myelination and regeneration in the peripheral nervous system. Whereas, little is known about the inducing effects by which the hormones exert their effects on Schwann cells differentiation. This could be revealed by the expression of Schwann cell markers in adipose-derived stem cells (ADSCs). The purpose of this study was to present the effects of progesterone and 17 β-estradiol on the Schwann cell markers in rat ADSCs. The mesenchymal stem cell markers (CD73, and CD90) were assayed by flow cytometry. Rat ADSCs were sequentially treated with β-mercaptoethanol, and all-trans-retinoic acid, followed by a mixture of basic fibrobroblast growth factor, platelet-derived growth factor, forskolin and heregulin. In experimental groups, forskolin and heregulin were substituted by progesterone and 17 β-estradiol. After induction, the expression of Schwann cell markers P0, and S-100 and the cellular immunocytochemical staining positive rate of anti-S100 and anti-glial fibrillary acidic protein (GFAP) antibodies were compared in the experimental and control groups. Progesterone and 17 β-estradiol triggered P0 and S-100 genes expression and induced a cellular immunocytochemical staining positive rate of S-100 and GFAP in rats ADSCs. Progesterone induced these changes stronger than 17 β-estradiol. Thus, progesterone may induce rat ADSCs toward Schwann-like cells by expression of Schwann cell markers and is more potent than 17 β-estradiol in the expression of these markers. © 2018 Urmia University. All rights reserved

Studying the users’ information-seeking behavior by recording brain waves activity with Electroencephalography method: A systematic Review

Despite the novelty in methodologies, User behavior study based on brain activity during information-seeking stages has become popular among information science researchers. This paper reviews scientific publications in which information-seeking behavior has been studied along with recorded brain activity to shed light on research status, challenges, and suggestions for future studies. Based on Kitchenham & Charters (2007) framework, a complete web search was performed in English and Persian scientific databases, and 22 publications in English were found as the final result, from 2007 to 2020. Review results demonstrate that exploring the user status (10 papers) and brain wave activity during information-seeking episodes (12 papers) were the most dominant subjective approaches in the field of user behavior studies. Cognitive load was found as an effective cognitive component on user status. With eye movement measurement and brain waves frequency study, 3 factors were found effective on cognitive load level generated during information searching and processing: searching media type, information representation, and text reading style. Brain wave activity and pupil dilation analysis were the most important measures in user status during search stages, and alpha and theta band waves were demonstrated as an index for cognitive load measurement during the information searching process. A correlation among eye data, search behavior, task complexity based on user experience, and cognitive style – as another effective factor on user status- led to results in different information searching behavior demonstrations. Also, 3 main stages were analyzed in the information-seeking process, based on brain wave activity: information exploring and query formulation, query reformulation and selection, relevance judgment, and decision making. Results showed a difference between brain activity areas, and differences in pupil dilation change level and alpha/beta frequency level during different search episodes. For future research, some suggestions were offered based on reviews. Finding relations between correlations among cognitive styles, task features, and domain knowledge during information searching process, personalized information retrieval improvement, more collaboration between information science and neurocognitive specialists, research in more user affective status like aggression and fatigue during the search process, using more economic methods and portable devices aiming to reduce research costs and expenses, facilitating larger sample studies and designing standard tasks were considered as a suggestion. Finally, some challenges were found based on reviewed studies. Some concepts like relevance feedback in information retrieval need more investigation. Also, it is necessary to investigate and explore user affections during the search process with multiple approaches

Melatonin and cancer: From the promotion of genomic stability to use in cancer treatment

Cancer remains among the most challenging human diseases. Several lines of evidence suggest that carcinogenesis is a complex process that is initiated by DNA damage. Exposure to clastogenic agents such as heavy metals, ionizing radiation (IR), and chemotherapy drugs may cause chronic mutations in the genomic material, leading to a phenomenon named genomic instability. Evidence suggests that genomic instability is responsible for cancer incidence after exposure to carcinogenic agents, and increases the risk of secondary cancers following treatment with radiotherapy or chemotherapy. Melatonin as the main product of the pineal gland is a promising hormone for preventing cancer and improving cancer treatment. Melatonin can directly neutralize toxic free radicals more efficiently compared with other classical antioxidants. In addition, melatonin is able to regulate the reduction/oxidation (redox) system in stress conditions. Through regulation of mitochondrial nction and inhibition of pro-oxidant enzymes, melatonin suppresses chronic oxidative stress. Moreover, melatonin potently stimulates DNA damage responses that increase the tolerance of normal tissues to toxic effect of IR and may reduce the risk of genomic instability in patients who undergo radiotherapy. Through these mechanisms, melatonin attenuates several side effects of radiotherapy and chemotherapy. Interestingly, melatonin has shown some synergistic properties with IR and chemotherapy, which is distinct from classical antioxidants that are mainly used for the alleviation of adverse events of radiotherapy and chemotherapy. In this review, we describe the anticarcinogenic effects of melatonin and also its possible application in clinical oncology. © 2018 Wiley Periodicals, Inc

A systematic review of radiation-induced testicular toxicities following radiotherapy for prostate cancer

Background: Prostate cancer is the second most common malignancy in men in the world, and radiotherapy is used as a standard treatment modality for this cancer. Although this treatment modality effectively kills prostate cancerous cells, it unavoidably irradiates the organs/tissues that are away from the treatment site. In this regard, radiation-induced testicular toxicities following prostate radiotherapy can affect sexual function, reproduction, and quality of life in cancer survivors. This review summarizes the available data on testicular exposure to radiation during prostate radiotherapy and the consequences on testicular function. Methods: To illuminate the radiation-induced testicular toxicities following prostate radiotherapy, a systematic search was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline in PubMed, Web of Science, Scopus, Embase, and clinical trials electronic databases up to September 2018. According to a set of prespecified inclusion and exclusion criteria, 31 eligible articles providing data on testicular function following radiotherapy in patients with prostate cancer were included in the study. Results: According to the different radiotherapeutic techniques used for prostate cancer treatment, the total tumor dose and scattered testicular dose values were ranging from 36.25 to 78.00 Gy and 0.06 to 6.48 Gy, respectively. Luteinizing hormone and follicle-stimulating hormone levels after prostate radiotherapy were signi�cantly higher in comparison with the pretreatment levels. Around 60 of the studies showed that testosterone levels after prostate radiotherapy were signi�cantly lower than the pretreatment levels. Furthermore, erectile dysfunction (ED), as an adverse side effect resulting from prostate radiotherapy, was reported and this complication is signi�cantly correlated with lower satisfaction with sexual life. Testicular atrophy following prostate radiotherapy has also been observed and its frequency in patients with prior prostate radiotherapy is 2.5 times more than that in the patients without prior radiotherapy. Conclusion: The data revealed that the scattered dose to testicular tissues during prostate radiotherapy can lead to testicular atrophy, variation of the male sex hormones, and quality of sexual life. © 2019 Wiley Periodicals, Inc

Melatonin as an adjuvant in radiotherapy for radioprotection and radiosensitization

It is estimated that more than half of cancer patients undergo radiotherapy during the course of their treatment. Despite its beneficial therapeutic effects on tumor cells, exposure to high doses of ionizing radiation (IR) is associated with several side effects. Although improvements in radiotherapy techniques and instruments could reduce these side effects, there are still important concerns for cancer patients. For several years, scientists have been trying to modulate tumor and normal tissue responses to IR, leading to an increase in therapeutic ratio. So far, several types of radioprotectors and radiosensitizers have been investigated in experimental studies. However, high toxicity of chemical sensitizers or possible tumor protection by radioprotectors creates a doubt for their clinical applications. On the other hand, the protective effects of these radioprotectors or sensitizer effects of radiosensitizers may limit some type of cancers. Hence, the development of some radioprotectors without any protective effect on tumor cells or low toxic radiosensitizers can help improve therapeutic ratio with less side effects. Melatonin as a natural body hormone is a potent antioxidant and anti-inflammatory agent that shows some anti-cancer properties. It is able to neutralize different types of free radicals produced by IR or pro-oxidant enzymes which are activated following exposure to IR and plays a key role in the protection of normal tissues. In addition, melatonin has shown the ability to inhibit long-term changes in inflammatory responses at different levels, thereby ameliorating late side effects of radiotherapy. Fortunately, in contrast to classic antioxidants, some in vitro studies have revealed that melatonin has a potent anti-tumor activity when used alongside irradiation. However, the mechanisms of its radiosensitive effect remain to be elucidated. Studies suggested that the activation of pro-apoptosis gene, such as p53, changes in the metabolism of tumor cells, suppression of DNA repair responses as well as changes in biosynthesis of estrogen in breast cancer cells are involved in this process. In this review, we describe the molecular mechanisms for radioprotection and radiosensitizer effects of melatonin. Furthermore, some other proposed mechanisms that may be involved are presented. © 2018, Federación de Sociedades Españolas de Oncología (FESEO)

The correlation among deposition parameters, structure and corrosion behaviour of ZnNi/nano-SiC composite coating deposited by pulsed and pulsed reverse current

The present work shows how the parameters of pulsed current (PC) deposition affect structural and morphological characteristics of electrodeposited ZnNi/nano-SiC composite coating and its corrosion properties. In this regard, ZnNi coatings containing SiC nanoparticles were electrodeposited from chloride bath by PC and pulsed reverse current (PRC) methods, and the effect of duty cycle, frequency and reverse current density were studied. With low and high duty cycles the SiC content of the coating was more than the coating deposited by medium duty cycle. Changing the duty cycle affected the coating composition, structure and morphology. Elevation of the pulse frequency increased SiC content of the coating. Application of PRC produced a coating with a complex and dendritic structure. In most of the electrodeposition conditions, in addition to direct effects of PC on coatings characteristics, it was seen that the more SiC was deposited in the coating the less Ni was deposited, and this also affected the corrosion behaviour. The best corrosion resistance behaviour was shown by coatings with more compact structure and less porosity

The correlation among deposition parameters, structure and corrosion behaviour of ZnNi/nano-SiC composite coating deposited by pulsed and pulsed reverse current

The present work shows how the parameters of pulsed current (PC) deposition affect structural and morphological characteristics of electrodeposited ZnNi/nano-SiC composite coating and its corrosion properties. In this regard, ZnNi coatings containing SiC nanoparticles were electrodeposited from chloride bath by PC and pulsed reverse current (PRC) methods, and the effect of duty cycle, frequency and reverse current density were studied. With low and high duty cycles the SiC content of the coating was more than the coating deposited by medium duty cycle. Changing the duty cycle affected the coating composition, structure and morphology. Elevation of the pulse frequency increased SiC content of the coating. Application of PRC produced a coating with a complex and dendritic structure. In most of the electrodeposition conditions, in addition to direct effects of PC on coatings characteristics, it was seen that the more SiC was deposited in the coating the less Ni was deposited, and this also affected the corrosion behaviour. The best corrosion resistance behaviour was shown by coatings with more compact structure and less porosity

Blooming gelatin: an individual additive for enhancing nanoapatite precipitation, physical properties, and osteoblastic responses of nanostructured macroporous calcium phosphate bone cements

Ziba Orshesh, Saeed Hesaraki, Ali Khanlarkhani Biomaterials Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center, Alborz, Iran Abstract: In recent years, there has been a great interest in using natural polymers in the composition of calcium phosphate bone cements to enhance their physical, mechanical, and biological performance. Gelatin is a partially hydrolyzed form of collagen, a natural component of bone matrix. In this study, the effect of blooming gelatin on the nanohydroxyapatite precipitation, physical and mechanical properties, and cellular responses of a calcium phosphate bone cement (CPC) was investigated. Various concentrations of blooming gelatin (2, 5, and 8 wt.%) were used as the cement liquid and an equimolar mixture of tetracalcium phosphate and dicalcium phosphate was used as solid phase. The CPC without any gelatin additive was also evaluated as a control group. The results showed that gelatin accelerated hydraulic reactions of the cement paste, in which the reactants were immediately converted into nanostructured apatite precipitates after hardening. Gelatin molecules induced 4%–10% macropores (10–300 µm) into the cement structure, decreased initial setting time by ~190%, and improved mechanical strength of the as-set cement. Variation in the above-mentioned properties was influenced by the gelatin concentration and progressed with increasing the gelatin content. The numbers of the G-292 osteoblastic cells on gelatin-containing CPCs were higher than the control group at entire culture times (1–14 days), meanwhile better alkaline phosphatase (ALP) activity was determined using blooming gelatin additive. The observation of cell morphologies on the cement surfaces revealed an appropriate cell attachment with extended cell membranes on the cements. Overall, adding gelatin to the composition of CPC improved the handling characteristics such as setting time and mechanical properties, enhanced nanoapatite precipitation, and augmented the early cell proliferation rate and ALP activity. Keywords: calcium phosphate cement, nanoapatite, cell studies, macroporosity, bone substitute, blooming gelati