Magnetic Hyperthermia as an adjuvant cancer therapy in combination with radiotherapy versus radiotherapy alone for recurrent/progressive glioblastoma: a systematic review

Introduction: Hyperthermia therapy (HT) is a recognized treatment modality, that can sensitize tumors to the effects of radiotherapy (RT) and chemotherapy by heating up tumor cells to 40�45 °C. The advantages of noninvasive inductive magnetic hyperthermia (MH) over RT or chemotherapy in the treatment of recurrent/progressive glioma have been confirmed by several clinical trials. Thus, here we have conducted a systematic review to provide a concise, albeit brief, account of the currently available literature regarding this topic. Methods: Five databases, PubMed/Medline, Embace, Ovid, WOS, and Scopus, were investigated to identify clinical studies comparing overall survival (OS) following RT/chemotherapy versus RT/chemotherapy + MH. Results: Eleven articles were selected for this systematic review, including reports on 227 glioma patients who met the study inclusion criteria. The papers included in this review comprised nine pilot clinical trials, one non-randomized clinical trial, and one retrospective investigation. As the clinical trials suggested, MH improved OS in primary glioblastoma (GBM), however, in the case of recurrent glioblastoma, no significant change in OS was reported. All 11 studies ascertained that no major side effects were observed during MH therapy. Conclusion: Our systematic review indicates that MH therapy as an adjuvant for RT could result in improved survival, compared to the therapeutic outcomes achieved with RT alone in GBM, especially by intratumoral injection of magnetic nanoparticles. However, heterogeneity in the methodology of the most well-known studies, and differences in the study design may significantly limit the extent to which conclusions can be drawn. Thus, further investigations are required to shed more light on the efficacy of MH therapy as an adjuvant treatment modality in GBM. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature

COVID-19 under spotlight: A close look at the origin, transmission, diagnosis, and treatment of the 2019-nCoV disease

Months after the outbreak of a new flu-like disease in China, the entire world is now in a state of caution. The subsequent less-anticipated propagation of the novel coronavirus disease, formally known as COVID-19, not only made it to headlines by an overwhelmingly high transmission rate and fatality reports, but also raised an alarm for the medical community all around the globe. Since the causative agent, SARS-CoV-2, is a recently discovered species, there is no specific medicine for downright treatment of the infection. This has led to an unprecedented societal fear of the newly born disease, adding a psychological aspect to the physical manifestation of the virus. Herein, the COVID-19 structure, epidemiology, pathogenesis, etiology, diagnosis, and therapy have been reviewed. © 2020 Wiley Periodicals, Inc

Application of Nanobiotechnology for Early Diagnosis of SARS-CoV-2 Infection in the COVID-19 Pandemic

Abstract: A most discussed topic of the new decade, COVID-19 is an infectious disease caused by the recently discovered SARS-CoV-2. With an exceedingly high transmission rate, COVID-19 has affected almost all the countries in the world. Absent any vaccine or specific treatment, the humanity is left with nothing but the legacy method of quarantine. However, quarantine can only be effective when combined with early diagnosis of suspected cases. With their high sensitivity and unmatched specificity, biosensors have become an area of interest for development of novel diagnostic methods. Compared to the more traditional diagnostics, nanobiotechnology introduces biosensors as different diagnostics with greater versatility in application. Today, a growing number of analytes are being accurately identified by these nanoscopic sensing machines. Several reports of validated application with real samples further strengthen this idea. As of recent, there has been a rise in the number of studies on portable biosensors. Despite the slow progression, certain devices with embedded biosensors have managed to be of diagnostic value in several countries. The perceptible increase in development of mobile platforms has revolutionized the healthcare delivery system in the new millennium. The present article reviews the most recent advancements in development of diagnostic nanobiosensors and their application in the clinical fields. Key points: � There is no specific treatment for highly transmissible SARS-CoV-2. � Early diagnosis is critical for control of pandemic. � Highly sensitive/specific nanobiosensors are emerging assets against COVID-19. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature

A survey on health status of coldwater rearing and hatcheries fish farms in Iran (Mazandarn, Gilan, Ardebil, West Azerbaiejan, East Azerbaiejan and Kordestan provinces)

The national research plan with title of "Study on health status of Iran Coldwater hatchery and rearing farms" was done in order to identification and tracking of main causative agents of recent mortality in Iran Coldwater hatchery and rearing farms and recognize of infected zones and design of landscape distribution of Epizootic Coldwater fish diseases in the country. This plan was conducted parallel and in same time in some polar provinces of Coldwater fish production such as Mazandaran, Gilan, Ardebil, West Azerbaijan, East Azerbaijan and Kurdistan in three years from 2006-2008. In this regard, about 23,21 and 20 farms in Mazandaran province, 30 farms in West and East Azerbaijan and Kurdistan provinces and 19 farms in Gilan and Ardebil were selected as randomly and tracking were done yearly from 2006-2008. This research was conducted according to regular planning consists of farms visit that was done according to statistical plan and completion of Questionnaires and sampling. The findings in Mazandaran province revealed that fish infections background and infectious diseases were increased in period of 2006-2008. In fact, 56% of all fish farms in 2006, 71% in 2007 and 85% in 2008 were recorded as infected farms. In other side, average weight of fish final products was more 500gr in consume market. So, regarding to long period of fish culture in mentioned fish occurrence of more morbidity could be expected. The streptococcus infections were most important fish bacterial diseases that have more incidence and pathogenicity in collected questionnaires. Also it revealed more occurrences in summer season in above 15oC temperature in affected fish farms. Also, Enteric Redmouth Disease (ERM) and Saprolegniasis were reported as second and third degree in examined farms. Meanwhile, findings of control, prevention and treatment of our survey revealed that using of antibiotics and detergent materials were increased in mentioned province. Indeed, 34.7% of all fish farms in 2006, 71.4% in 2007 and 75% in 2008 have applied treatment operation and using of detergent materials in affected farms. In other side, frequent using of Erythromycin antibiotic was reported several times in 2008 so fish farmer faced to Bacterial resistance and should be using from Florfenicol as alternative antibacterial. Also, in feed sampling from all fish farms about 3 fish farms in 2006 and 5 fish farms in 2008 were faced with food poisoning that originated from high TVN and peroxidase in fish food consumed. These farms revealed mass mortality that stopped after change feeding regime. In conclusion absence of fish health management could be considered as main agent of mentioned mortality in Mazandaran province. The findings of our survey in West and East Azerbaijan and Kurdistan revealed that absence of sufficient experiences in fish farmers and their neglect from water quality concepts, farm cleanness, using of suitable detergent materials for fish ponds and instruments and disability in continuous monitoring of physic-chemical factors of consumed water could be considered as most important problems. So, fish morbidity and mortality, growth decrement and low production rate were expected. Unfortunately, despite the occurrence of infectious and non- infectious diseases in examined fish farms, there were no documents and information about diseases history, clinical signs in dead fish, feeding regime, fish mortality (rate of daily mortality, age and weight of moribund fish), treatment operation, drugs usage, growth rate, physico-chemical factors and fish density. So planning for control and prevention of mentioned diseases were unsuccessful in affected fish farms. Also, occurrence of some epizootic fish viral diseases such as VHS, IPN and IHN were observed frequently with mass mortality about 40100% in some examined fish farms that produced some tragic economic lost in the mentioned provinces. Similarly, some bacterial, fungal and parasitic diseases were observed repeatedly in some inspected farms such as Flavobacterium, streptococcus infections. Also, some unknown causative agents in parasitic diseases were observed several times such as Dactylogyrus, Gyrodactylus, Ichthyophthirius multifiliis, Trichodina, Chilodonella, Diplostomum and fungal diseases such as Saprolegniasis. In conclusion it seems that absence of fish health management, inadequate rate of hygienic technical services, absence of quarantine programs for transfer of new eyed-eggs, juvenile and live broodstocks packages without health certificates from authorized organizations, uncontrolled entry of foreign eyed-eggs (France, Denmark, Australia and Armenia) and neglect in using of suitable detergent materials for fish ponds, instruments, consumed water and infected eggs, not screening of broodstocks in hatcheries could be considered as most important causative agents in occurrence of infectious diseases and main problems in affected farms in mentioned provinces. Similarly, our findings in Gilan and Ardebil provinces revealed that their problems were similar to other provinces. In fact, neglect in establish of necessary Infrastructures in fish farms and dereliction in health management concepts could be considered as main reasons of occurrence of fish infectious and non-infectious diseases in studied fish farms in mentioned provinces. In fact, often fish farms visited hadn't suitable structures without control and prevention approach. There were not observed detergent using, quarantine programs and prevention methods. Entrance of unknown persons, birds and wild animals were ordinary in mentioned farms. Unfortunately level of farmer’s knowledge was low and no training courses and extension programs were planned by authorized organizations. Meanwhile, food storages were unsuitable and food packages were stored in inappropriate situation so poisoning conditions were increased in examined farms. In conclusion it could be finalized that Coldwater fish farms in Gilan and Ardebil provinces situated in insufficient position and correction of current situation are needed urgently. In final elicitation, it would be mentioned that lack of basic infrastructures could be introduced as most important reasonfor spread of diseases, mortality and related economic losses in studied provinces. Therefore, attention to environmental affairs and access to Sustainable Development are recommended. Also consideration of biosecurity regulations and health management concepts would be important requirements for modification and reformation of Coldwater fish farms in examined provinces towards A Better Tomorrow

Axonal transport proteins and depressive like behavior, following Chronic Unpredictable Mild Stress in male rat

Background: A common mood disorder, depression has long been considered a leading cause of disability worldwide. Chronic stress is involved in the development of various psychiatric diseases including major depressive disorder. Stress can induce depressive-like symptoms and initiate neurodegenerative processes in the brain. The neurodegenerative theory of depression holds impaired axonal transport as a negative factor in neural survival. Axonal transport is a critical mechanism for normal neuronal function, playing crucial roles in axon growth, neurotransmitter secretion, normal mitochondrial function and neural survival. Methods and materials: To investigate the effects of stress-induced depression, in the present study, we evaluated behavior by forced swimming test (FST), corticosterone plasma level by ELISA assay, hippocampal mRNA expression of three genes (NGF, kinesin and dynein) via real-time PCR and hippocamp count by Nissl staining in male Wistar rats. Results: Our data demonstrated a significant decrease in the expression of NGF, kinesin and dynein genes in CUMS groups compared to the control group (non-stressed) (p < 0.05). CUMS also caused an elevation in immobility time and corticosterone plasma level in the stressed group compared to the controls (p < 0.01 and p < 0.05, respectively). Conclusion: The results suggested that the possibility of stress-induced depressive behavior associated with hippocampal neurodegeneration process is correlated with a low expression of kinesin and dynein, the two most important proteins in axonal transport. © 2018 Elsevier Inc

Evaluation of the effect of hyperthermia and electron radiation on prostate cancer stem cells

The aim of this study was to investigate the effect of hyperthermia, 6 MeV electron radiation and combination of these treatments on cancer cell line DU145 in both monolayer culture and spheroids enriched for prostate cancer stem cells (CSCs). Flowcytometric analysis of the expression of molecular markers CD133+/CD44+ was carried out to determine the prostate CSCs in cell line DU145 grown as spheroids in serum-free medium. Following monolayer and spheroid culture, DU145 cells were treated with different doses of hyperthermia, electron beam and combination of them. The survival and self-renewing of the cells were evaluated by colony formation assay (CFA) and spheroid formation assay (SFA). Flowcytometry results indicated that the percentage of CD133+/CD44+ cells in spheroid culture was 13.9-fold higher than in the monolayer culture. The SFA showed significant difference between monolayer and spheroid culture for radiation treatment (6 Gy) and hyperthermia (60 and 90 min). The CFA showed significantly enhanced radiosensitivity in DU145 cells grown as monolayer as compared to spheroids, but no effect of hyperthermia. In contrast, for the combination of radiation and hyperthermia the results of CFA and SFA showed a reduced survival fraction in both cultures, with larger effects in monolayer than in spheroid culture. Thus, hyperthermia may be a promising approach in prostate cancer treatment that enhances the cytotoxic effect of electron radiation. Furthermore, determination and characterization of radioresistance and thermoresistance of CSCs in the prostate tumor is the key to develop more efficient therapeutic strategies. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature

Axonal transport proteins and depressive like behavior, following Chronic Unpredictable Mild Stress in male rat

Background: A common mood disorder, depression has long been considered a leading cause of disability worldwide. Chronic stress is involved in the development of various psychiatric diseases including major depressive disorder. Stress can induce depressive-like symptoms and initiate neurodegenerative processes in the brain. The neurodegenerative theory of depression holds impaired axonal transport as a negative factor in neural survival. Axonal transport is a critical mechanism for normal neuronal function, playing crucial roles in axon growth, neurotransmitter secretion, normal mitochondrial function and neural survival. Methods and materials: To investigate the effects of stress-induced depression, in the present study, we evaluated behavior by forced swimming test (FST), corticosterone plasma level by ELISA assay, hippocampal mRNA expression of three genes (NGF, kinesin and dynein) via real-time PCR and hippocamp count by Nissl staining in male Wistar rats. Results: Our data demonstrated a significant decrease in the expression of NGF, kinesin and dynein genes in CUMS groups compared to the control group (non-stressed) (p < 0.05). CUMS also caused an elevation in immobility time and corticosterone plasma level in the stressed group compared to the controls (p < 0.01 and p < 0.05, respectively). Conclusion: The results suggested that the possibility of stress-induced depressive behavior associated with hippocampal neurodegeneration process is correlated with a low expression of kinesin and dynein, the two most important proteins in axonal transport. © 2018 Elsevier Inc

Thermosensitive magnetic nanoparticles exposed to alternating magnetic field and heat-mediated chemotherapy for an effective dual therapy in rat glioma model

The goal of this study was to develop a new method based on Oncothermia with concomitant use of the temozolomide (TMZ)-loaded magnetic nanoparticles conjugated with folic acid (TMZ/MNPs-FA) and alternative magnetic field (AMF) and evaluate its efficacy in the treatment of C6 glioma in rats. TMZ/MNPs-FA were prepared and evaluated for their size, surface charge, magnetic saturation, hemolysis and in vitro AMF-triggered release. The glioma rat models were treated with free TMZ, MNPs-FA and TMZ/MNPs-FA in the presence or absence of AMF (43 °C). The results confirmed that a combinatorial therapy consisting of AFM hyperthermia and thermosensitive TMZ/MNPs-FA could significantly suppress tumor growth, increase survival rate and promote apoptosis (P < 0.0001). Therefore, this treatment strategy may be a powerful modality for treatment of cancer, as the thermal and mechanical effects of magnetic nanoparticles exposed to AMF can increase the therapeutic efficacy of conventional chemotherapy. © 2020 Elsevier Inc

Evaluation of the effect of hyperthermia and electron radiation on prostate cancer stem cells

The aim of this study was to investigate the effect of hyperthermia, 6 MeV electron radiation and combination of these treatments on cancer cell line DU145 in both monolayer culture and spheroids enriched for prostate cancer stem cells (CSCs). Flowcytometric analysis of the expression of molecular markers CD133+/CD44+ was carried out to determine the prostate CSCs in cell line DU145 grown as spheroids in serum-free medium. Following monolayer and spheroid culture, DU145 cells were treated with different doses of hyperthermia, electron beam and combination of them. The survival and self-renewing of the cells were evaluated by colony formation assay (CFA) and spheroid formation assay (SFA). Flowcytometry results indicated that the percentage of CD133+/CD44+ cells in spheroid culture was 13.9-fold higher than in the monolayer culture. The SFA showed significant difference between monolayer and spheroid culture for radiation treatment (6 Gy) and hyperthermia (60 and 90 min). The CFA showed significantly enhanced radiosensitivity in DU145 cells grown as monolayer as compared to spheroids, but no effect of hyperthermia. In contrast, for the combination of radiation and hyperthermia the results of CFA and SFA showed a reduced survival fraction in both cultures, with larger effects in monolayer than in spheroid culture. Thus, hyperthermia may be a promising approach in prostate cancer treatment that enhances the cytotoxic effect of electron radiation. Furthermore, determination and characterization of radioresistance and thermoresistance of CSCs in the prostate tumor is the key to develop more efficient therapeutic strategies. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature

Enhancement radiation-induced apoptosis in C6 glioma tumor-bearing rats via pH-responsive magnetic graphene oxide nanocarrier

5-iodo-2-deoxyuridine (IUdR) has been demonstrated to induce an appreciable radiosensitizing effect on glioblastoma patients, but due to the short circulation half-life times and failure to pass through the blood-brain barrier (BBB), its clinical use is limited. Accordingly, in this study, we used magnetic graphene oxide (NGO/SPIONs) nanoparticles coated with PLGA polymer as a dynamic nanocarrier for IUdR and, evaluated its sensitizing enhancement ratio in combination with a single dose X-ray at clinically megavoltage energies for treatment of C6 glioma rats. Nanoparticles were characterized using Zetasizer and TEM microscopy, and in vitro biocompatibility of nanoparticles was assessed with MTT assay. IUdR/MNPs were intravenously administered under a magnetic field (1.3 T) on day 13 after the implantation of C6 cells. After a day following the injection, rats exposed with radiation (8 Gy). ICP-OES analysis data indicated an effective magnetic targeting, leading to remarkably improved penetration through the BBB. In vivo release analysis with HPLC indicated sustained release of IUdR and, prolonged the lifespan in plasma (P 100), prolonged the survival time (>100) and suppressed the anti-apoptotic response of glioma rats by increasing Bax/Bcl-2 ratio (2.13-fold) in compared with the radiation-only. In conclusion, besides high accumulation in targeted tumor sites, the newly developed IUdR/MNPs, also exhibited the ability of IUdR/MNPs to significantly enhance radiosensitizing effect, improve therapeutic efficacy and increase toxicity for glioma-bearing rats. © 2020 Elsevier B.V