Impact of an Okinawa/Nordic based diet on endocrinological and periodontal conditions in individuals with type 2 diabetes. A randomized case-control study.

OBJECTIVES: To assess if the results following intake of a diet using an Okinawan-based Nordic diet (OBND) over one month differs in endocrinological, periodontal clinical outcome, and serum cytokine levels compared to a standard hospital care diet in individuals with diabetes type 2 (T2D) (control group). BACKGROUND: Scientific evidence suggests that the use of diet for individuals with T2D may be beneficial. METHODS: Participating individuals with T2D were randomly assigned to a test (OBND) (n = 14), or control group (n = 16). Anthropometric data, blood glucose levels, HbA1c levels, lipids, serum inflammation markers (CRP, and a routine panel of 24 cytokines), blood pressure, gingival bleeding on probing (BOP), probing pocket depths (PPD), and clinical attachment levels (CAL) were studied. RESULTS: Statistical analyses of baseline study data failed to demonstrate study group differences. The mean weight reduction was greater in the OBND group (4.1 kg) versus the control group (1.3 kg) (p < 0.01). The reduction in BMI was 1.4 kg/m2 in OBND (p < 0.001) and 0.5 kg/m2 in the control group, respectively (p < 0.01). Diastolic and systolic blood pressure reductions were greater in the OBND group than in the control group (p < 0.01). Periodontal study parameters (BOP % scores) and (PPD values) decreased (p < 0.001) overall with no between group differences. The OBND resulted in reduction of serum levels of IFNγ, Eotaxin IL-9, IP10,IL17a, MCP-1,m and PDFBB compared to the control diet. CONCLUSIONS: A strict T2D- diet provides an association between reduction in serum HbA1c and BOP scores. Serum levels decreases in IFNγ, Eotaxin IL-9, IP-10, IL17a. MCP-1, and PDFBB were only found in the test group.

Alpha-Lipoic Acid and Its Enantiomers Prevent Methemoglobin Formation and DNA Damage Induced by Dapsone Hydroxylamine: Molecular Mechanism and Antioxidant Action.

Dapsone (DDS) therapy can frequently lead to hematological side effects, such as methemoglobinemia and DNA damage. In this study, we aim to evaluate the protective effect of racemic alpha lipoic acid (ALA) and its enantiomers on methemoglobin induction. The pre- and post-treatment of erythrocytes with ALA, ALA isomers, or MB (methylene blue), and treatment with DDS-NOH (apsone hydroxylamine) was performed to assess the protective and inhibiting effect on methemoglobin (MetHb) formation. Methemoglobin percentage and DNA damage caused by dapsone and its metabolites were also determined by the comet assay. We also evaluated oxidative parameters such as SOD, GSH, TEAC (Trolox equivalent antioxidant capacity) and MDA (malondialdehyde). In pretreatment, ALA showed the best protector effect in 2.5 µg/mL of DDS-NOH. ALA (1000 µM) was able to inhibit the induced MetHb formation even at the highest concentrations of DDS-NOH. All ALA tested concentrations (100 and 1000 µM) were able to inhibit ROS and CAT activity, and induced increases in GSH production. ALA also showed an effect on DNA damage induced by DDS-NOH (2.5 µg/mL). Both isomers were able to inhibit MetHb formation and the S-ALA was able to elevate GSH levels by stimulating the production of this antioxidant. In post-treatment with the R-ALA, this enantiomer inhibited MetHb formation and increased GSH levels. The pretreatment with R-ALA or S-ALA prevented the increase in SOD and decrease in TEAC, while R-ALA decreased the levels of MDA; and this pretreatment with R-ALA or S-ALA showed the effect of ALA enantiomers on DNA damage. These data show that ALA can be used in future therapies in patients who use dapsone chronically, including leprosy patients.

AuNPs with Cynara scolymus leaf extracts rescue arsenic-induced neurobehavioral deficits and hippocampal tissue toxicity in Balb/c mice through D1R and D2R activation.

The present study was designed to evaluate whether AuNPs (gold nanoparticles) synthesized with the Cynara scolymus (CS) leaf exert protective and/or alleviative effects on arsenic (As)-induced hippocampal neurotoxicity in mice. Neurotoxicity in mice was developed by orally treating 10 mg/kg/day sodium arsenite (NaAsO2) for 21 days. 10 µg/g AuNPs, 1.6 g/kg CS, and 10 µg/g CS-AuNPs were administered orally simultaneously with 10 mg/kg As. CS and CS-AuNPs treatments showed down-regulation of TNF-α and IL-1ß levels. CS and CS-AuNPs also ameliorated apoptosis and reduced the alterations in the expression levels of D1 and D2 dopamine receptors induced by As. Simultaneous treatment with CS and CS-AuNPs improved As-induced learning, memory deficits, and motor coordination in mice assessed by water maze and locomotor tests, respectively. The results of this study provide evidence that CS-AuNPs demonstrated neuroprotective roles with antioxidant, anti-inflammatory, and anti-apoptotic effects, as well as improving D1 and D2 signaling, and eventually reversed neurobehavioral impairments.

Brain-derived neurotrophic factor as an indicator of chemical neurotoxicity: an animal-free CNS cell culture model.

Recent changes to the legislation on chemicals and cosmetics testing call for a change in the paradigm regarding the current 'whole animal' approach for identifying chemical hazards, including the assessment of potential neurotoxins. Accordingly, since 2004, we have worked on the development of the integrated co-culture of post-mitotic, human-derived neurons and astrocytes (NT2.N/A), for use as an in vitro functional central nervous system (CNS) model. We have used it successfully to investigate indicators of neurotoxicity. For this purpose, we used NT2.N/A cells to examine the effects of acute exposure to a range of test chemicals on the cellular release of brain-derived neurotrophic factor (BDNF). It was demonstrated that the release of this protective neurotrophin into the culture medium (above that of control levels) occurred consistently in response to sub-cytotoxic levels of known neurotoxic, but not non-neurotoxic, chemicals. These increases in BDNF release were quantifiable, statistically significant, and occurred at concentrations below those at which cell death was measureable, which potentially indicates specific neurotoxicity, as opposed to general cytotoxicity. The fact that the BDNF immunoassay is non-invasive, and that NT2.N/A cells retain their functionality for a period of months, may make this system useful for repeated-dose toxicity testing, which is of particular relevance to cosmetics testing without the use of laboratory animals. In addition, the production of NT2.N/A cells without the use of animal products, such as fetal bovine serum, is being explored, to produce a fully-humanised cellular model.

Dapsone is an anticatalysis for Alzheimer's disease exacerbation.

Brain inflammation generally accelerates neurodegeneration. Alzheimer's disease (AD) triggers an innate immune response by activating a cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. Our study investigated patients with leprosy and AD. They were treated with dapsone (4,4'-diaminodiphenyl sulfone, DDS) as a neuroinflammasome competitor and cGAS/STING pathway inhibitor. Four groups were defined: Treatment (T) 1: DDS prescribed AD diagnosed, T 2: DDS prescribed AD undiagnosed, T 3 DDS unprescribed AD diagnosed, and T 4: DDS unprescribed AD undiagnosed. Dapsone effects on AD can be clearly distinguished according to dapsone presence or absence. T1:T3 proved that the incidence of AD was significantly reduced by dapsone. T2:T3 proved that the prevalence of AD was significantly high without dapsone. T1:T4 proved that the prevalence decreased when taking dapsone. Our study demonstrates that dapsone can prevent AD exacerbation and may represent a preventive therapeutic option for exacerbated AD.

Increased connectivity of hiPSC-derived neural networks in multiphase granular hydrogel scaffolds.

To reflect human development, it is critical to create a substrate that can support long-term cell survival, differentiation, and maturation. Hydrogels are promising materials for 3D cultures. However, a bulk structure consisting of dense polymer networks often leads to suboptimal microenvironments that impedes nutrient exchange and cell-to-cell interaction. Herein, granular hydrogel-based scaffolds were used to support 3D human induced pluripotent stem cell (hiPSC)-derived neural networks. A custom designed 3D printed toolset was developed to extrude hyaluronic acid hydrogel through a porous nylon fabric to generate hydrogel granules. Cells and hydrogel granules were combined using a weaker secondary gelation step, forming self-supporting cell laden scaffolds. At three and seven days, granular scaffolds supported higher cell viability compared to bulk hydrogels, whereas granular scaffolds supported more neurite bearing cells and longer neurite extensions (65.52 ± 11.59 µm) after seven days compared to bulk hydrogels (22.90 ± 4.70 µm). Long-term (three-month) cultures of clinically relevant hiPSC-derived neural cells in granular hydrogels supported well established neuronal and astrocytic colonies and a high level of neurite extension both inside and beyond the scaffold. This approach is significant as it provides a simple, rapid and efficient way to achieve a tissue-relevant granular structure within hydrogel cultures.

A dissection of SARS­CoV2 with clinical implications (Review).

We are being confronted with the most consequential pandemic since the Spanish flu of 1918­1920 to the extent that never before have 4 billion people quarantined simultaneously; to address this global challenge we bring to the forefront the options for medical treatment and summarize SARS­CoV2 structure and functions, immune responses and known treatments. Based on literature and our own experience we propose new interventions, including the use of amiodarone, simvastatin, pioglitazone and curcumin. In mild infections (sore throat, cough) we advocate prompt local treatment for the naso­pharynx (inhalations; aerosols; nebulizers); for moderate to severe infections we propose a tried­and­true treatment: the combination of arginine and ascorbate, administered orally or intravenously. The material is organized in three sections: i) Clinical aspects of COVID­19; acute respiratory distress syndrome (ARDS); known treatments; ii) Structure and functions of SARS­CoV2 and proposed antiviral drugs; iii) The combination of arginine­ascorbate.

Short-term effects of very low dose cadmium feeding on copper, manganese and iron homeostasis: A gastropod perspective.

The available information on the interplay between low-dose cadmium intake and copper, manganese, and iron homeostasis in invertebrates is limited. We have currently studied the accumulation of these trace metals in the hepatopancreas of adult snails, Cantareus aspersus, following 14 and 28 days of exposure to low doses of dietary cadmium, up to 1 mg/kg dw (dry weight). The cadmium dose, but not the duration of exposure, had a significant effect on hepatopancreas copper deposition, the values being significantly elevated compared to controls. A significant peak in manganese levels at 14 days was found in snails administered the lowest cadmium dose. These increases occurred even in the absence of cadmium increase in the hepatopancreas. Our data suggest that low dose cadmium feeding can produce a transient disturbance in hepatopancreas copper and manganese homeostasis. Such responses may serve as early biomarkers of physiological changes occurring during the initial stages of cadmium intoxication.

Dapsone induces oxidative stress and impairs antioxidant defenses in rat liver.

Dapsone (DDS) is currently used in the treatment of leprosy, malaria and in infections with Pneumocystis jirovecii and Toxoplasma gondii in AIDS patients. Adverse effects of DDS involve methemoglobinemia and hemolysis and, to a lower extent, liver damage, though the mechanism is poorly characterized. We evaluated the effect of DDS administration to male and female rats (30 mg/kg body wt, twice a day, for 4 days) on liver oxidative stress through assessment of biliary output and liver content of reduced (GSH) and oxidized (GSSG) glutathione, lipid peroxidation, and expression/activities of the main antioxidant enzymes glutathione peroxidase, superoxide dismutase, catalase and glutathione S-transferase. The influence of DDS treatment on expression/activity of the main DDS phase-II-metabolizing system, UDP-glucuronosyltransferase (UGT), was additionally evaluated. The involvement of dapsone hydroxylamine (DDS-NHOH) generation in these processes was estimated by comparing the data in male and female rats since N-hydroxylation of DDS mainly occurs in males. Our studies revealed an increase in the GSSG/GSH biliary output ratio, a sensitive indicator of oxidative stress, and in lipid peroxidation, in male but not in female rats treated with DDS. The activity of all antioxidant enzymes was significantly impaired by DDS treatment also in male rats, whereas UGT activity was not affected in any sex. Taken together, the evidence indicates that DDS induces oxidative stress in rat liver and that N-hydroxylation of DDS was the likely mediator. Impairment in the activity of enzymatic antioxidant systems, also associated with DDS-NHOH formation, constituted a key aggravating factor.

Further preliminary assessment of three human glioma cell lines as models of human astrocytic toxicity in vitro.

Three human astroglioma lines U251-MG, U373-MG and CCF-STTG1 have been evaluated further as possible models for astrocytotoxicity (GFAP and IL-6 release). The effects of bacterial lipopolysaccharide, chloroquine diphosphate and acrylamide were studied on GFAP expression and LPS, chloroquine diphosphate, ethanol, trimethyltin chloride (TMTC) and acrylamide were examined on interleukin-6 (IL-6) release in the U373-MG line only. At 4-h LPS elevated GFAP (17.0±5.0% P<0.05) above control in the U251-MG cell line only. Chloroquine diphosphate over 4h in the U251-MG line resulted in an increase in GFAP-IR to 20.3±4.2% and 21.1±4.1% above control levels 0.1µM (P<0.05) and 1µM (P<0.05) respectively. CQD was associated with decreases in MTT turnover, particularly after 24h incubation. With the U373-MG line, LPS (0.5µg/ml) increased IL-6 expression 640% above control (P<0.001), whilst chloroquine diphosphate (100µM), ethanol (10mM) and TMTC chloride (1µM) also increased IL-6. It is possible that batteries of astrocytic human glioma cell lines may be applicable to the sensitive evaluation of toxicants on astrogliotic expression markers such as GFAP and IL-6.

In vitro Models for Seizure-Liability Testing Using Induced Pluripotent Stem Cells.

The brain is the most complex organ in the body, controlling our highest functions, as well as regulating myriad processes which incorporate the entire physiological system. The effects of prospective therapeutic entities on the brain and central nervous system (CNS) may potentially cause significant injury, hence, CNS toxicity testing forms part of the "core battery" of safety pharmacology studies. Drug-induced seizure is a major reason for compound attrition during drug development. Currently, the rat ex vivo hippocampal slice assay is the standard option for seizure-liability studies, followed by primary rodent cultures. These models can respond to diverse agents and predict seizure outcome, yet controversy over the relevance, efficacy, and cost of these animal-based methods has led to interest in the development of human-derived models. Existing platforms often utilize rodents, and so lack human receptors and other drug targets, which may produce misleading data, with difficulties in inter-species extrapolation. Current electrophysiological approaches are typically used in a low-throughput capacity and network function may be overlooked. Human-derived induced pluripotent stem cells (iPSCs) are a promising avenue for neurotoxicity testing, increasingly utilized in drug screening and disease modeling. Furthermore, the combination of iPSC-derived models with functional techniques such as multi-electrode array (MEA) analysis can provide information on neuronal network function, with increased sensitivity to neurotoxic effects which disrupt different pathways. The use of an in vitro human iPSC-derived neural model for neurotoxicity studies, combined with high-throughput techniques such as MEA recordings, could be a suitable addition to existing pre-clinical seizure-liability testing strategies.

A closer look at neuron interaction with track-etched microporous membranes.

Microporous membranes support the growth of neurites into and through micro-channels, providing a different type of neural growth platform to conventional dish cultures. Microporous membranes are used to support various types of culture, however, the role of pore diameter in relation to neurite growth through the membrane has not been well characterised. In this study, the human cell line (SH-SY5Y) was differentiated into neuron-like cells and cultured on track-etched microporous membranes with pore and channel diameters selected to accommodate neurite width (0.8 µm to 5 µm). Whilst neurites extended through all pore diameters, the extent of neurite coverage on the non-seeded side of the membranes after 5 days in culture was found to be directly proportional to channel diameter. Neurite growth through membrane pores reduced significantly when neural cultures were non-confluent. Scanning electron microscopy revealed that neurites bridged pores and circumnavigated pore edges - such that the overall likelihood of a neurite entering a pore channel was decreased. These findings highlight the role of pore diameter, cell sheet confluence and contact guidance in directing neurite growth through pores and may be useful in applications that seek to use physical substrates to maintain separate neural populations whilst permitting neurite contact between cultures.

Physiological and anthocyanin biosynthesis genes response induced by vanadium stress in mustard genotypes with distinct photosynthetic activity.

The present study aimed to elucidate the photosynthetic performance, antioxidant enzyme activities, anthocyanin contents, anthocyanin biosynthetic gene expression, and vanadium uptake in mustard genotypes (purple and green) that differ in photosynthetic capacity under vanadium stress. The results indicated that vanadium significantly reduced photosynthetic activity in both genotypes. The activities of the antioxidant enzymes were increased significantly in response to vanadium in both genotypes, although the purple exhibited higher. The anthocyanin contents were also reduced under vanadium stress. The anthocyanin biosynthetic genes were highly expressed in the purple genotype, notably the genes TT8, F3H, and MYBL2 under vanadium stress. The results indicate that induction of TT8, F3H, and MYBL2 genes was associated with upregulation of the biosynthetic genes required for higher anthocyanin biosynthesis in purple compared with the green mustard. The roots accumulated higher vanadium than shoots in both mustard genotypes. The results indicate that the purple mustard had higher vanadium tolerance.

Toxicity of plant extracts containing pyrrolizidine alkaloids using alternative invertebrate models.

Pyrrolizidine alkaloids (PAs) are a widespread class of hepatotoxic heterocyclic organic compounds found in approximately 3% of world flora. Some PAs have been shown to have genotoxic and carcinogenic effects. The present study focuses on the toxicity effects of four dry extracts obtained from medicinal plants (Senecio vernalis, Symphytum officinale, Petasites hybridus and Tussilago farfara), on two aquatic organisms, Artemia salina and Daphnia magna, and the correlation with their PAs content. A new GC­MS method, using a retention time (TR)­5MS type capillary column was developed. PAs Kovats retention indices, for this type of column were computed for the first time. The lethal dose 50% (LC50) values for the two invertebrate models were correlated (Pearson 's coefficient, >0.9) and the toxicity was PA concentration-dependent, for three of the four extracts. All tested extracts were found to be toxic in both aquatic organism models. The results can be used to develop a GC­MS validated method for the assay of PAs in medicinal plants with a further potential application in the risk assessment study of PAs toxicity in humans.

Assessment of the astrogliotic responses of three human astrocytoma cell lines to ethanol, trimethyltin chloride and acrylamide.

The astrogliotic responses of the CCF-STTG1, U251-MG, and U373-MG human astrocytoma lines were determined after exposure to ethanol, trimethyltin chloride (TMTC), and acrylamide over 4, 16, and 24h. Basal glial fibrillary acidic protein (GFAP) expression in the U-251MG and U373-MG cells was 10-fold greater than the CCF-STGG1 line. Ethanol treatment over 24h, but not at 4 and 16h, resulted in significant increases in GFAP in all three glioma lines at sub-cytotoxic levels; the GFAP responses in the CCF-STTG1 line were the most sensitive, as concentrations of 0.1 and 1mM led to increases in GFAP expression compared with control of 56.8+/-15.7 and 58.9+/-11.5%, respectively (P<0.05). Treatment with TMTC (1 microM) over 4h showed elevated GFAP expression in the U251-MG cell line to 28.0+/-15.7% above control levels (P<0.01), but not in the other U373-MG or CCF-STTG1 cells. At 4h, MTT turnover was markedly increased compared with control, particularly in the U373-MG line at concentrations as low as 1 microM (17.1+/-2.3%; P<0.01). TMTC exposure over 16 and 24h resulted in reduction in GFAP expression in all three lines at concentrations; at 24h incubation, the reduction was >50% (P<0.01). There were no changes in GFAP expression or MTT turnover in response to acrylamide except at the highest concentration ranges of 10-100 mM. This study underlines the significance of period of exposure, as well as toxin concentration in astrocytoma cellular response to toxic pressure.

Apoptotic and necrotic effects of hexanedione derivatives on the human neuroblastoma line SK-N-SH.

The potential cytotoxicity of two hexanedione food additives (2,3 and 3,4 isomers) was evaluated in comparison with the neurotoxic hexane metabolite 2,5-hexanedione in the human SK-N-SH neuroblastoma line using the MTT assay to indicate mitochondrial dehydrogenase activity and flow cytometry to monitor the cell cycle over 48 h. The IC(50)s of the 2,3-hexanedione (3.3+/-0.1 mM) and 3,4-hexanedione (3.5+/-0.1 mM), indicated that the sensitivity of the cells was approximately seven-fold greater to these toxins compared with the 2,5 derivative (IC(50) of 22.4+/-0.2 mM). Comparison between the respective IC(50)s of the 2,3-hexanedione and 3,4-hexanedione revealed no difference between the two isomers in terms of their effects on MTT turnover. With flow cytometry analysis, all three hexanediones showed increases in apoptosis within their respective concentration ranges of toxicity shown previously by MTT. In the presence of 2,5-hexanedione, between 8.5 and 17 mM concentrations, there was a significant increase in apoptotic nucleoids which was accompanied by a significant fall in the percentage of nucleoids in the G0/G1 phase (72.4+/-0.3-45.3+/-0.6%,), and a rise in the numbers of cells in the G2/M phase. This is likely to indicate growth arrest at cell cycle G2/M checkpoint in response to toxin damage. G2/M accumulation was also shown with 3,4 and 2,3 HD, which was maximal at much lower concentrations (approximately 4 and 3mM, respectively). Arrest at G1 and G2/M phase is indicative of inhibition of the cell cycle at the stages of DNA replication and chromosome segregation, respectively. It was also apparent that flow cytometry, rather than the MTT assay, did distinguish between the effects of the alpha-diketones 2,3-hexanedione and 3,4-hexanedione on the cell cycle. At a concentration of 5.8mM 3,4-hexanedione, the percentage of apoptotic nucleoids was 10.9+/-0.8% whilst apoptosis induced by 3,4-hexanedione had already reached a maximal level of 60.4+/-0.5%. In summary, flow cytometry indicated that the 3,4-hexanedione derivative was more toxic than its 2,3 isomer and that both food additives caused interruption in the neuroblastoma cell cycle and further investigation may be required to assess if these alpha-diketones present in diets pose any possible risks to human health.

Effects of lipoic acid and dihydrolipoic acid on total erythrocytic thiols under conditions of restricted glucose in vitro.

The effects of lipoic acid and dihydrolipoic acid were explored on total thiol maintenance in diabetic and non-diabetic human erythrocytes in vitro over 22 hr in a 37 degrees C incubation system with no added glucose. Over 18-22.5 hr after treatment in both non-diabetic and diabetic cells, lipoic acid (1 mM) was associated with greater loss of cellular thiols than dihydrolipoic acid (1 mM), compared to respective control values. At 0.1 mM, in non-diabetic cells, although lipoic acid-treated cells' thiol levels were significantly lower than control, there was no significant difference between dihydrolipoic acid-treated cells and control cells regarding thiol levels. In addition, at 0.1 mM, dihydrolipoic acid-treated diabetic cells showed a reduction in thiol levels compared to control. At 0.01 mM, lipoic acid-treated cells had significantly lower measured thiol levels compared with diabetic cells exposed to dihydrolipoic acid, whereas in non-diabetic cells, dihydrolipoic acid-treated erythrocytic thiol levels were significantly greater than those treated with lipoic acid, although there were no other significant differences between the groups. At 22.5 hr, control values of methaemoglobin rose to 6.4 +/- 1.1% in diabetic cells and 3.6 +/- 2.1% in non-diabetic cells. Lipoic acid (1 mM) showed greater methaemoglobin formation in diabetic rather than non-diabetic cells (13.6 +/- 1.5% versus 11.6 +/- 1.5%), whereas dihydrolipoic acid-treated diabetic and non-diabetic cells were less potent in methaemoglobin generation (8.5 +/- 2.4% and 8.4 +/- 1.4%, respectively). These studies suggest that in certain circumstances such as hypoglycaemia, lipoic acid administration may actually be detrimental to cellular oxidant protection status.

How drug metabolism influences treatment outcomes.

Recent developments within the National Health Service have led to an increase in personnel 'qualified' to prescribe a wide range of pharmacological agents. A short (38-day) Continuing Professional Development course in prescribing is deemed adequate to fully train individuals for practice. A sound understanding of prescribing medicines has important implications for patient benefit. For example, a prescriber would require some knowledge of drug absorption, distribution, metabolism and excretion, as well as aspects of drug delivery and drug-drug interactions. Drug metabolism in particular exerts a powerful influence on drug action; this can range from complete failure of efficacy through to life-threatening toxicity. Moreover, it is conservatively estimated that there may be several thousand deaths each year in the UK arising from an inadequate knowledge of drug metabolism when prescribing medicines. This one-day course focused on the importance of understanding drug metabolism on treatment strategies and outcomes, and was accessed by a range of healthcare professionals in the West Midlands area of the UK.

Impact on environment, ecosystem, diversity and health from culturing and using GMOs as feed and food.

Modern agriculture provides the potential for sustainable feeding of the world's increasing population. Up to the present moment, genetically modified (GM) products have enabled increased yields and reduced pesticide usage. Nevertheless, GM products are controversial amongst policy makers, scientists and the consumers, regarding their possible environmental, ecological, and health risks. Scientific-and-political debates can even influence legislation and prospective risk assessment procedure. Currently, the scientifically-assessed direct hazardous impacts of GM food and feed on fauna and flora are conflicting; indeed, a review of literature available data provides some evidence of GM environmental and health risks. Although the consequences of gene flow and risks to biodiversity are debatable. Risks to the environment and ecosystems can exist, such as the evolution of weed herbicide resistance during GM cultivation. A matter of high importance is to provide precise knowledge and adequate current information to regulatory agencies, governments, policy makers, researchers, and commercial GMO-releasing companies to enable them to thoroughly investigate the possible risks.