Research Article | DOI: https://doi.org/10.31579/IJBR-2021/009
Division of Health Sciences and Engineering, University of Guanajuato, Campus Celaya-Salvatierra, México.
*Corresponding Author: Vicente Beltrán-Campos, Division of Health Sciences and Engineering, University of Guanajuato, Campus Celaya-Salvatierra, México.
Citation: Vicente B. Campos, Yolanda T. Rosas, Xóchitl S. R. Gómez1, Sandra N.J. García, Cuauhtémoc S. Salazar, María I. Vargas and Sofía Y. D. Miranda (2021) Chronic consumption of 4(5)-Methylimidazole generates alterations in the spatial memory and synaptic plasticity of the rat, International J. of Biomed Research 1(3); DOI: 10.31579/IJBR-2021/009
Copyright: © 2021 Vicente Beltrán-Campos, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 15 March 2021 | Accepted: 29 March 2021 | Published: 08 May 2021
Keywords: 4 (5) -methylimidazole; hippocampus; neurotoxicity, memory
4(5)-methylimidazole (4(5)-MEI), used as an additive in the food industry. A neurotoxic effect is reported in experimental animals, with alterations in the cellular structure of the central nervous system. Evidence to demonstrate alterations in synaptic connectivity is lacking. The objective was to determine the neurotoxic effect of 4(5)-MEI, at the structural level of the synaptic connectivity of the rat dorsal hippocampus. Eighteen Sprague Dawley rats divided into 3 groups: control and 2 experimental with oral intake of 4(5)-MEI (625 and 1250 ppm), for 24 weeks. Morris water maze test was performed. Animals were sacrificed, serum malondialdehyde (MDA) levels were determined, and the dorsal hippocampus was removed for quantification of dendritic spines. The MDA determination did not show significant differences between the groups. The groups treated with 4(5)-MEI, showed a deterioration in spatial memory with respect to the control group and a decrease in the density of dendritic spines of the dorsal hippocampus. Chronic consumption of 4(5)-MEI does not increase serum MDA levels. However, exerts a neurotoxic effect by decreasing the performance of the rat on a spatial memory task, this can be correlated with the decrease in the density of dendritic spines.
4(5)-Methylimidazole (4(5)-MEI), is a nitrogen-containing heterocyclic compound, belongs to class III and IV of ammonia caramel dyes, and is widely used as an additive in the food industry, unfortunately Carcinogenic and neurotoxic properties have been attributed to it in laboratory animals, so efforts are being made to limit its use in food [1]. Because of this, various studies have focused on identifying the presence of 4(5)-MEI in food and beverages, using analytical techniques such as high-performance liquid chromatography coupled to mass spectrometry, to quantify small amounts of this compound [2]. On the other hand, toxicological studies continue to be carried out to determine the deleterious effects that 4(5)-Methylimidazole, when consumed in high concentrations and for long periods of time, since in 2007 The United States Institute of Public Health through d The National Toxicology Program carried out a long-term toxicity study, evaluating the effects of 4(5)-MEI on female and male rodents exposed for 2 years at concentrations of 625, 1250 and 2500 ppm and 312, 625 and 1250 ppm. Respectively. At the end of the study, the development of lung cancer in mice and leukemia in rats was observed with the highest concentration [3, 4].
In another study, it was reported that the administration of 4(5)-MEI at concentrations of 300, 800 and 2500 ppm in B6C3F1 mice and F344/N rats for 15 days, did not induce histopathological changes in these rodents. Instead, the administration for 14 weeks of the same compound in these laboratory specimens at concentrations of 625, 1,250, 2,500, 5,000 and 10,000 ppm; they did not modify the serum levels of T(3), T(4) and TSH and did not produce thyroid lesions. Tremors and ataxia were observed only in the high-dose groups.5 Anemia, hepatocytic vacuolation, testicular degeneration, and prostatic atrophy were also observed in both mice and rats.6 However, the study of the neurotoxic effect has not been investigated so far of 4(5)-MEI, most toxicological studies have focused on the carcinogenic effect [6, 7]. Furthermore, there is evidence that at high doses and long exposure times 4(5)-MEI affects the central nervous system,[8] so it is of particular interest to assess whether chronic exposure to oral administration of 4(5)-MEI in water ad libitum is capable of modifying the function of cognitive activities of learning and memory, and the spinal plasticity of the hippocampus to through the production of oxidative stress in this anatomical structure, which can thus affect the rat's spatial memory.
Animals and experimental groups
Eighteen rats of the Sprague-Dawley strain, weighing 200 ± 5 g at the start of the experiment, divided into three groups with n = 6 each were used. All the rats were placed in 40x60x30cm transparent acrylic boxes, in a room that had a controlled temperature of 22 to 25 ° C, and a light-dark cycle of 12:12 hours, beginning the light period at 7:00. Hours . They were divided into 3 groups: 1) Control Group (CG), with food and water ad libitum; 2) Group that was administered 4 (5) -methylimidazole orally (v.o.) dissolved in water ad libitum at 625ppm, (G625ppm); and 3) Group that was administered 4(5)-methylimidazole by v.o. dissolved in water ad libitum at 1250ppm, (G1250pmm), for 24 continuous weeks[5].
Morris Aquatic Maze Test (MAM)
The MAM used is a black circular plastic tank with a diameter of 150 cm and a height of 60 cm placed on a metal base that supports it at a height of 58 cm. It was filled with water to a height of 30 cm maintaining a temperature of 25 ° C ± 1 ° C. The four starting positions were marked on the external face of the tank with the four cardinal axes North (N), South (S), East (E), West(W), thus dividing into 4 quadrants. A black plastic platform with dimensions of 10 x 10 cm, submerged at 1 cm, was placed under the surface of the water.
The hidden platform aquatic maze paradigm was used, the training and test schedules ranged between 10:00 and 13:00. The training procedure was as follows: Animals were tested in one session of 8 trials. In each, the animal was placed inside the tank facing the wall at one of the randomly designated starting points (North, South, East,West); the animal could escape the aversive stimulus of the water by finding and climbing on the escape platform. Different starting points were used in each trial, and each of these points was used 2 times within the trials. The escape platform was in the lower left quadrant in all trials and the first exit point was west of the tank; in the second the exit point was placed to the North of the tank, the third point was placed to the South and the fourth point to the East; at the fifth point she moved back to the north, the sixth exit point to the south, the seventh point to the east and the eighth exit point to the west.
If any animal did not enter the escape platform, during the 60 second test time, it was manually guided to the escape platform, only during the first test. After climbing on the platform, the rats remained there for 20 seconds and were then removed from the maze, dried with a cotton towel and placed in a resting box for an interval of 30 seconds, to then start the next test. The latency of arrival at the escape platform, measured in seconds (s), was used to determine the acquisition.
In the analysis of the data obtained by the repeated measures ANOVA test during the three learning sessions with four trials per day, no statistically significant differences were observed between the control group and the experimental groups (F(2,18) = 0.414, p = 0.6672), on the other hand regarding the training day if statistically significant differences were observed (F(2,15) = 7.989, p = 0.0002), as well as in the interaction between the variables (F(2,6) = 9.521, p <0>
Retention was assessed 24 hours after the end of training. The retention consisted of a 2 min session where the escape platform was removed from the tank. The rat was positioned facing the labyrinth wall at the west exit point; and she was allowed to swim freely during this time;At the end of this, the rat withdrew from the maze, to dry it and place it in a resting box for 30 seconds, after which it was returned to its room box to finish the task. For its evaluation, the latency in seconds and the number of entrances to the place where the platform was located were considered.
Obtaining the brain and blood plasma
To obtain the brain and blood plasma, the animals were decapitated after anesthesia with xylazine / ketamine (40 mg/kg). At the time of decapitation, the blood was collected in test tubes of 1 x 10 cm, they were placed inside a clinical centrifuge at a speed of 3000 rpm for 30 min separating the serum into eppendorf tubes. On the other hand, the head was dissected to the cranial cavity and the brain was separated from it and immersed in a mixture with mercury chloride, potassium dichromate and distilled water for its preparation by means of Golgi Cox staining.
Once the brains were obtained by decapitation, they were immersed in 50 milliliters of a mixture with mercury chloride, potassium dichromate and distilled water, for a period of 30 days. Subsequently, they were rinsed and dehydrated in alcohol graduated from 50 to 95% for 30 min in each change. They were transferred to a mixture of alcohol/acetone 50ml/50ml, for 24 hours. They were included in a low nitrocellulose solution at consecutive concentrations of 5, 10, 15 and 30%. They were placed in molds with 30% nitrocellulose in chloroform vapors for subsequent cutting in a sliding microtome at 120 micrometers thick, collecting the sections in a container with 70% alcohol. They were hydrated in distilled water and differentiated in a photographic developer solution for 2 min. They were washed with distilled water. They were dehydrated in alcohol graduated from 70 to 95% and placed in isopropyl alcohol for 10 min, for subsequent mounting in resin and observation under a microscope.
Lipid peroxidation technique (LP)
To determine the plasma PL, the measurement of malondialdehyde levels (MDA) was used by the fluorometric method, using the lipid peroxidation test kit (colorimetric/fluorometric), (abcam 118970), according to the manufacturer's specifications.
Ethical and legal considerations
All the animals were housed, handled, and slaughtered based on the provisions of the Official Mexican Standard NOM-062-ZOO-1999, Technical Specifications for the production, care and use of laboratory animals [9].This project was authorized by the research committee of the University of Guanajuato Campus Celaya-Salvaterra and registered with No. CIDSC2700923.
The IBM SPSS Statistics version 23 program was used. For the statistical analysis of weight gain and latency time during acquisition, the repeated measures ANOVA test was applied. For the analysis of retention latency time, entrances to the platform site and quantification of dendritic spines, the one-way ANOVA test was applied. Followed by Tukey's post hoc test. The level of significance was established with p<0.05.
In the analysis of the weight gain of the animals using the repeated measures ANOVA test, statistically significant differences were observed in the category by group (F(2.90) = 7.566, p = 0.0053), in the category by weight it was observed a statistically significant difference (F(2, 6) = 114.052, p <0 xss=removed xss=removed>
Acquisition Test
In the analysis of the data obtained by the repeated measures ANOVA test during the three learning sessions with four trials per day, no statistically significant differences were observed between the control group and the experimental groups (F(2,18) = 0.414, p = 0.6672), on the other hand regarding the training day if statistically significant differences were observed (F(2,15) = 7.989, p = 0.0002), as well as in the interaction between the variables (F(2,6) = 9.521, p <0>
The analysis of the levels obtained from MDA, by means of the fluorometric test by means of the ELISA technique, was carried out by applying the one-way ANOVA test. The data obtained from plasma MDA levels do not show statistically significant differences between the control group and the experimental groups (F(2.15) = 0.165, p = 0.8493). (Figure 2).
The analysis of the results obtained by the one-way ANOVA, regarding the arrival latency during the memory retention test, statistically significant differences were observed between the control group and the experimental groups (F(2.15) = 13.947, p = 0.0004), Tukey's post hoc test determined significant differences between the control group and the group that received 625 ppm of 4(5)-MEI (p = 0.0003) and between the control group and the group that received 1250 ppm of 4(5)-MEI (p = 0.0006), not so, between the groups that received 625 ppm and 1250 ppm of 4(5)-MEI (p = 7007). (Figure 4).
Regarding the number of entries to the place where the platform was located in the memory retention test, the analysis of the data using the one-way ANOVA showed statistically significant differences (F(2.15) = 6,743, p = 0.0081) , between the CG and the experimental groups G625ppm and G1250ppm, not so between both experimental groups G625ppm and G1250ppm (p = 0.6075) (Figure 5).
The one-way ANOVA test on the density of dendritic spines shows statistically significant differences between the CG and the experimental groups (F(2.78) = 5.526, p = 0.0057). This shows that the density of spines along the apical dendrite is modified by the consumption of 4(5)-MEI. Tukey's post hoc test reveals that the GC maintains a higher density of dendritic spines with respect to G625 (p = 0.007), and G1250 (p = 0.0036). However, no differences are shown when comparing both experimental groups. (Figure 6).
4(5)-Methylimidazole (4(5)-MEI), is a neurotoxic agent, which exerts a convulsive effect at high doses and changes in the cellular structure (necrosis) of various regions of the central nervous system.8 Few are the studies sponsored in the different databases that show a direct relationship between the toxic effect on the effective brain region and its function. This study is a first attempt to deepen this relationship. The data obtained from the plasma MDA levels of the groups exposed to both experimental treatments showed no differences with respect to the plasma MDA levels of the control animals, the treatment time was probably not sufficient to alter the activity of the antioxidants. endogenous. This is probably due to the fact that the lipid unsaturation that promotes the autoxidation rate increases the complexity of the product distribution; and it can change depending on the experimental conditions (or different in vivo environments) [10]. The results obtained by subjecting the animals to a test that values learning and spatial memory showed that under this scheme of chronic exposure with 625 and 1250 ppm of 4(5)-MEI during 24 weeks, the control group and the experimental ones behaved similarly in the performance of the training stage (learning). However, when performing the 24 hour retention test, after the training sessions, both experimental groups showed a low performance of the task, increasing the arrival latency time and decreasing the number of entries to the quadrant where the platform, with respect to the control group. However, the behavior of both experimental groups was similar when compared to each other. This behavior exhibited by both experimental groups could represent that despite the fact that the animals exposed for 24 weeks with the 4(5)-MEI, had an acquisition similar to the controls, this could not be remembered, so the test where memory recall was required was overcome only by the control group.
In the same way, we have not found studies that directly correlate the exposure by 4(5)-MEI, with alterations of cellular metabolism at the cerebral level, proposing in this case that these results are the first report in the field of neurodegeneration. Our results, therefore, support a possible relationship between the ability of 4(5)-MEI to produce oxidative stress, through the formation of lipid oxidation products, that is, the formation of MDA adducts, mainly at the hippocampus level. the rat. This product is a mutagenic α, β-unsaturated aldehyde that is commonly used as a biomarker for LPO through testing of the substance that reacts with thiobarbituric acid (TBARS) [11]. Probably the oxidative state as a result of exposure to 4(5) -MEI, explain how every neurodegeneration process, where in a balanced redox state, neurons and their supporting cells coexist in a healthy environment [12]. After induction of nitrative oxidative stress in an unbalanced redox state, a Neuroinflammatory condition due to microglial activation that undergoes morphological changes as factories producing EROS / RNS through positive regulation and release of cytokines such as interleukin-1, interleukin-6, tumor necrosis factor α, interferon-γ; increased inducible nitric oxide synthase (iNOS), which increases NO levels; increased production of EROS; and the stimulation of the formation of dopamine quinone in which dopamine-quinones regulate the expression of the neuroprotective gene [13]. In addition to activating the chain function of the microglia, keeping it activated and generating changes in neighboring neurons, which can eventually present alterations functional or structural [14].Several articles support the neurotoxic effect of 4(5)-MEI, characterized by episodes of confusion, motor agitation or hyperexcitability, tremors and seizures.15 The findings obtained in experimental studies where very low concentrations of 4(5)-MEI in the diet and determined in the plasma of experimentally intoxicated animals, [15,16] has given way to being considered a seizure agent, [17] not being possible to differentiate between the clinical signs of experimental exposure with 4(5)-MEI and food poisoning [18]. Furthermore, this observation has been verified in animals under concentrations and controlled application. Laboratory tests such as those carried out in long-term fed and intoxicated rats [4]. Despite lethal doses, these experimental animals show signs of excitation of the central nervous system (tremors, squeaks and jumps, among others), which later become seizures and death [19, 20]. Which implies that perhaps 4(5)-MEI is involved in the activity of various neurotransmitters such as gamma-aminobutyric acid (GABA) [21, 22].
Chronic consumption of 4(5)-MEI does not increase serum MDA levels in experimental rats, which may suggest a time-dependent efficiency of antioxidant systems. However, it exerts a neurotoxic effect by decreasing the rat's performance on a spatial memory task. A correlation study is required between the function and anatomy of the brain areas involved in the performance of memory tasks. It is suggested that more studies be carried out that allow the analysis of the mechanisms that underlie the toxic effect caused by 4(5)-MEI, as well as the possible protection mechanisms that the organism develops when chronically exposed to this substance.
All the authors declare that they have no conflict of interest.
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Dear Jessica Magne, Editorial Coordinator, Clinical Cardiology and Cardiovascular Interventions, Auctores Publishing LLC. I appreciate the journal (JCCI) editorial office support, the entire team leads were always ready to help, not only on technical front but also on thorough process. Also, I should thank dear reviewers’ attention to detail and creative approach to teach me and bring new insights by their comments. Surely, more discussions and introduction of other hemodynamic devices would provide better prevention and management of shock states. Your efforts and dedication in presenting educational materials in this journal are commendable. Best wishes from, Farahnaz Fallahian.
Dear Ashley Rosa, Editorial Coordinator of the journal - Psychology and Mental Health Care. " The process of obtaining publication of my article in the Psychology and Mental Health Journal was positive in all areas. The peer review process resulted in a number of valuable comments, the editorial process was collaborative and timely, and the quality of this journal has been quickly noticed, resulting in alternative journals contacting me to publish with them." Warm regards, Susan Anne Smith, PhD. Australian Breastfeeding Association.
Dear Jessica, and the super professional team of the ‘Clinical Cardiology and Cardiovascular Interventions’ I am sincerely grateful to the coordinated work of the journal team for the no problem with the submission of my manuscript: “Cardiometabolic Disorders in A Pregnant Woman with Severe Preeclampsia on the Background of Morbid Obesity (Case Report).” The review process by 5 experts was fast, and the comments were professional, which made it more specific and academic, and the process of publication and presentation of the article was excellent. I recommend that my colleagues publish articles in this journal, and I am interested in further scientific cooperation. Sincerely and best wishes, Dr. Oleg Golyanovskiy.
To Dear Erin Aust – Editorial Coordinator of Journal of General Medicine and Clinical Practice! I declare that I am absolutely satisfied with your work carried out with great competence in following the manuscript during the various stages from its receipt, during the revision process to the final acceptance for publication. Thank Prof. Elvira Farina
My article, titled 'No Way Out of the Smartphone Epidemic Without Considering the Insights of Brain Research,' has been republished in the International Journal of Clinical Case Reports and Reviews. The review process was seamless and professional, with the editors being both friendly and supportive. I am deeply grateful for their efforts.
We found the peer review process quick and positive in its input. The support from the editorial officer has been very agile, always with the intention of improving the article and taking into account our subsequent corrections.
Dear Jessica Magne, with gratitude for the joint work. Fast process of receiving and processing the submitted scientific materials in “Clinical Cardiology and Cardiovascular Interventions”. High level of competence of the editors with clear and correct recommendations and ideas for enriching the article.
I thank the ‘Journal of Clinical Research and Reports’ for accepting this article for publication. This is a rigorously peer reviewed journal which is on all major global scientific data bases. I note the review process was prompt, thorough and professionally critical. It gave us an insight into a number of important scientific/statistical issues. The review prompted us to review the relevant literature again and look at the limitations of the study. The peer reviewers were open, clear in the instructions and the editorial team was very prompt in their communication. This journal certainly publishes quality research articles. I would recommend the journal for any future publications.
"I am grateful for the opportunity of contributing to [International Journal of Clinical Case Reports and Reviews] and for the rigorous review process that enhances the quality of research published in your esteemed journal. I sincerely appreciate the time and effort of your team who have dedicatedly helped me in improvising changes and modifying my manuscript. The insightful comments and constructive feedback provided have been invaluable in refining and strengthening my work".
To Dear Erin Aust, I would like to express my heartfelt appreciation for the opportunity to have my work published in this esteemed journal. The entire publication process was smooth and well-organized, and I am extremely satisfied with the final result. The Editorial Team demonstrated the utmost professionalism, providing prompt and insightful feedback throughout the review process. Their clear communication and constructive suggestions were invaluable in enhancing my manuscript, and their meticulous attention to detail and dedication to quality are truly commendable. Additionally, the support from the Editorial Office was exceptional. From the initial submission to the final publication, I was guided through every step of the process with great care and professionalism. The team's responsiveness and assistance made the entire experience both easy and stress-free. I am also deeply impressed by the quality and reputation of the journal. It is an honor to have my research featured in such a respected publication, and I am confident that it will make a meaningful contribution to the field.
I would like to express my sincere gratitude for the support and efficiency provided by the editorial office throughout the publication process of my article, “Delayed Vulvar Metastases from Rectal Carcinoma: A Case Report.” I greatly appreciate the assistance and guidance I received from your team, which made the entire process smooth and efficient. The peer review process was thorough and constructive, contributing to the overall quality of the final article. I am very grateful for the high level of professionalism and commitment shown by the editorial staff, and I look forward to maintaining a long-term collaboration with the International Journal of Clinical Case Reports and Reviews.
Dear Agrippa Hilda- Editorial Coordinator of Journal of Neuroscience and Neurological Surgery, "The peer review process was very quick and of high quality, which can also be seen in the articles in the journal. The collaboration with the editorial office was very good."
I would like to offer my testimony in the support. I have received through the peer review process and support the editorial office where they are to support young authors like me, encourage them to publish their work in your esteemed journals, and globalize and share knowledge globally. I really appreciate your journal, peer review, and editorial office.
My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.
My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.
My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
