AUCTORES
Globalize your Research
Research Article | DOI: https://doi.org/10.31579/2578-8965/109
1Department of Anatomy, Yozgat Bozok University Faculty of Medicine, Yozgat, Turkey
2 Tekirdağ Namik Kemal University, Faculty of Medicine, Tekirdağ, Turkey
3 Department of Medical biology, Faculty of Medicine, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey.
4 Department of Anatomy, Erciyes University Faculty of Medicine, Kayseri, Turkey
5 Department of Biochemistry, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey
*Corresponding Author: Adem Tokpınar, Tekirdağ Namik Kemal University, Faculty of Medicine, Tekirdağ, Turkey
Citation: Yılmaz S., Tokpınar A., Ateş S., Köklü B., Evrim S. Arıkan, Uçar S. , Ayşe Yeşim G. (2022) Effects of Maternal Caffeine and Vitamin E Usage on Fetus. J. Obstetrics Gynecology and Reproductive Sciences 6(3); DOI: 10.31579/2578-8965/109
Copyright: © 2022, Adem Tokpınar, 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: 01 December 2021 | Accepted: 18 December 2021 | Published: 11 January 2022
Keywords: rat; pregnancy; ossification; caffeine; oxidative stress
The use of maternal caffeine has an important effect on the development of the fetus. We investigated the mechanism of oxidative damage induced by caffeine and the efficacy of vitamin E.
Pregnant rats of Wistar-albino genus were used. Following groups of animals were defined: control, sham, caffeine (50 mg/kg), caffeine + vitamin E, vitamin E (60 mg/kg) all invasive applications were repeated daily for 20 days. Tumor necrosis factor alpha (TNF-α), interleukin 1β(IL-1β), interleukin 6 (IL-6) levels were measured in tissue homogenates by using Enzyme-Linked Immuno Sorbent Assay (ELISA) method.
Thiobarbituric acid reactive acid substances (TBARS), Superoxide dismutase (SOD), Glutathione (GSH), Glutathione disulfide (GSSG), Total oxidant status (TOS), Total anti-oxidant status (TAS), Oxidative stress index (OSI), Calcium (Ca) and vitamin D (Vit D) parameters were measured by spectrophotometric assay.
According to these data, caffeine used in pregnancy delayed ossification; It has been found that vitamin E, a powerful antioxidant, counteracts this effect.
Caffeine, whose main natural sources are coffee, tea and cocoa, is one of the most popular and most consumed stimulants worldwide [1]. Since there are no enzymes that inactivate caffeine in the fetus, high caffeine intake can damage the fetus when the caffeine crosses the placental barrier. Epidemiological and experimental animal studies report that caffeine can cross the placental barrier and cause reproductive and developmental toxicities, including intrauterine growth retardation (IUGR) [2, 3].. However, it may cause also pregnancy complications such as pre-eclampsia by inducing oxidative stress formation. It was found that long bone dysplasia can be induced in juvenile rats in the case of prenatal caffeine exposure (PCE), accompanied by overexposure to maternal glucocorticoid. At the same time, it was found that endochondral ossification delay occurred with the suppression of chondrocyte terminal differentiation and the chondrocyte apoptosis rate decreased in the chondrocyte region [4,5]. On the other hand, high caffeine intake causes toxic effects in the kidney and therefore constitutes the basis for kidney diseases. In a study conducted in 2019, high levels of maternal glucocorticoids induced by PCE have been reported to cause podocyte development toxicity in offspring through gene expression programming of renal KLF4 [6].
Vitamin E is a powerful dietary antioxidant that is available in eight different forms and dissolves in fat. Vitamin E has been found to play a protective role in both mother and fetus during pregnancy under normal conditions. Low plasma vitamin E levels have been associated with pregnancy outcomes such as fetal growth [7].. It is thought that antioxidant function and membrane stabilizing effect mediate the molecular mechanism of vitamin E action, which plays a role in various physiological and biochemical functions [8].
The renin–angiotensin system (RAS) was originally considered to be a circulating system that regulated sodium and fluid balance and hemodynamics [9]. Angiotensin II is a potent vasoconstrictor and acts on the angiotensin receptors. Agtr2 (Angiotensin II Receptor Type 2) is part of the renin-angiotensin signaling (RAS) pathway that has been widely studied for its role in blood-pressure regulation [10]. In the present study, also we investigated the effect of high dose vitamin E and caffeine on the Agtr2 gene expression in the placenta of rats.However, when the necessary literature review was conducted, there were not enough studies investigating the effect of vitamin E, a powerful antioxidant against oxidative stress occurring in the fetus as a result of the use of high doses of caffeine in pregnants. In this context, the possible effects of vitamin E against the effects caused by maternal caffeine intake in the fetus organs; was investigated in terms of double skeletal staining, biochemical parameters, real-time PCR method and the number of pyramidal cells in the hippocampus.
Our study was approved by Erciyes University Animal Experiments Local Ethics Committee's decision dated 14.11.2018 and numbered 18/138. The care, feeding, agents applications of animals and sacrification of animals at the end of the experiment were carried out within the Experimental Research Application and Research Center.
Selection and Mating of Experimental Animals
In the study, 25 Wistar Albino female rats weighing an average of 185-200 g and at least 8 weeks old were used. Female rats to be used in the study were kept separately from male rats for 20 days. At the end of this period, the female rats, which were found not to be pregnant, were placed in the same cage together with the male rats (1 male rats to 2 female rats) in order to conceive. In the next step, vaginal smear samples from female rats were examined under a microscope. Female rats with spermium in vaginal smear samples were determined as 0.5 days pregnant.
Preparation of Injections
Caffeine powder (Sigma Aldrich USA (Cat number: 200-362-1)) and Vitamin E (Sigma Aldrich USA (Cat number: 500862)) were obtained from and both substances were prepared daily and no stock solution was made.
Experiment Groups
Details of the experimental groups are given in (Table 1, Fig. 1).
Manipulation of Rats and Obtaining Fetuses
Pregnant rats were anesthetized with ketamine (75 mg/kg) + xylazine (10 mg/kg) on the 20th day of pregnancy. Fetuses were dissected together with the placenta.
Skeletal Staining in Fetuses
All fetuses taken after the experiment were kept in 70% ethyl alcohol for 4-7 days and tissues were freed from water content. After this process, was kept in pure acetone for 1-3 days and degreased. Fetuses extracted from acetone were taken into a double staining solution formed with Alizarin Red-S (100 mg) and Alcian Blue (300 mg) in glass containers. The tissues were stained by incubating for 7 days. At the end of the 7th day, the fetuses were washed under running tap water for 2 hours and allowed to react with water. Then, 1% KOH solution was used to make the tissues transparent. These tissues were then transferred to 20%, 50% and 80% glycerin solutions, then into pure glycerin, respectively. For morphometric measurements, fetus extremities were photographed on a stereomicroscope with Nikon E5700 camera. Then, the obtained photos were transferred to computer. The length and area measurements of the bone to be examined in the transferred photographs were measured using Image J program.
Homogenization and Total Protein Extraction
For biochemical analyzes, after placenta liver and bone tissues were homogenized, was centrifuged at 14000 rpm for 15 minutes at +4 °C and supernatants were collected. Protein content of all samples was measured by Bradford method.
Antioxidant Indices and Cytokines Measurements
Activities of superoxide dismutase (SOD), the levels of glutathione (GSH) and glutathione disulfide (GSSG) were measured in tissue samples by the modified methods of Öztürk and Oztürk (2004) (11). Colorimetric kits (Relassay,Elabscience) were used to measure the levels of TAS,TOS, TNF-α, each sample was analyzed in duplicate. Glutathione content was calculated using the formula GSH = T-GSH − (2 × GSSG). The levels of GSH was calculated by the formula: GSH = GSHt−2 × GSSG. The results of GSHt, GSH, and GSSG were normalized to the total protein content and were expressed as nmol of GSH or GSSG per mg of protein (nmol GSH/mg protein or nmol GSSG/mg protein). OSI value was calculated using the formula: OSI = (TOS (μmol H2O2 equiv./l) / TAS (μmol trolox equiv./l) × 100). Lipid peroxidation, as an indicator of oxidative stress, was estimated by the measurement of TBARS in tissue homogenates as previously described by Buege [12]. Protein samples were thawed, and commercial ELISA kits were used for the quantitative measurement of TNF-α (Cat. No: E-EL-R0019, Elabscience USA), IL-1β (Cat. No: E-EL-R0012, Elabscience USA), IL-6 (Cat. No: E-EL-R0015, Elabscience USA) levels, according to the manufacturer’s instructions. Results are expressed in milligram per milliliter of proteins. ELISA was performed with protein samples extracted from tissues, according to the manufacturer’s instructions. Total Ca2+ concentration was evaluated by using calcium colorimetric assay kit (ab102505; Abcam) according to the manufacturer’s datasheet [13]. 25 µL of standard solution and 25 µL of supernatant extracted from tissue, diluted 1:10, were mixed with 45 µL of chromogenic reagent and 30 µL assay buffer. The mixture was incubated at room temperature for 15 minutes in the dark. The signal was screened at 575 nm (Thermo Varioscan). The concentration of calcium in the samples was calculated according to Sen 2018 (14). Vitamin D analysis was determined using the commercial ELISA kit (EIA 5396 DRG, Germany). Commercial enzyme-linked immunosorbent (ELISA) assay kits were used to measure the serum levels of cytokines (IL-6, TNF-α (Elabscience, MD, USA)).
Stereological Procedure
Optical disector method was applied to determine the number of pyramidal cells in the CA region of the hippocampus [28, 29]. The number of pyramidal neurons in the CA region of the hippocampus was calculated by cross-section sampling rate. We used a stereology workstation (Kayseri, Turkey) for stereological analyses. This system consisted of a CCD digital camera, an image capture card, a personal computer, a computer-controlled motorized specimen stage (Prior Scientific, Cambridge, UK), a microcator (Heidenhein Traunreut, Germany), and a light microscope (Leica, Nubloch, Germany). We used a software program (Macrobrightfield) to measure and record stereological data and to capture digital images of the sections. The system generated microscopy images (a 100× Leica HCX Plan Apo objective) and displayed them on a computer monitor to count the total number of pyramidal cells in the hippocampal CA regions. The total pyramidal neuron number in the CA region (N) of the hippocampus was calculated using the formula: N = Σ Q.
(N:Total neuron number,
ΣQ:Total disector neuron number,
ssf; Section sampling fraction,
asf:Area sampling fraction,
tsf:Thickness sampling fraction).
Briefly, if the largest nuclear profile came into focus within the unbiased virtual counting frames spaced randomly and systematically throughout the delineated regions, then the pyramidal cell was counted. The total pyramidal cell numbers were computed based on the number of pyramidal cells counted and the sampling probability [15, 16].
mRNA Gene Expression Studies
Total RNA was extracted from placental tissues with PureZole reagent (Biorad, USA, Cat. No: 732-6890) according to the manufacturer’s protocol. Then, RNA amount and RNA purity were quantified for each RNA sample by Nanodrop ND-1000 spectrophotometer V3.7. All the RNA samples were reverse transcribed into cDNA from 1 µg of total RNA (iScript Reverse Trancription Supermix Biorad, USA, Cat. No:170884) under the following conditions: One cycle at 25°C for 5 minutes, 46°C for 20 minutes and 95°C for 1 minute.
Agtr2 mRNA expression analysis performed by Rotor Gene-Q (Qiagen, Hilden, Germany). Appropriate dilued cDNA’as were added to a master mixture according to the manufacturer’s protocol (SsoAdvanced Universal Inhibitor-Tolerant SYBR Green Supermix, Biorad, USA, Cat. No: 172-50-16). Oligonucleotide primers were designed by Oligomere (Ankara, TURKEY) based on following primer sequences: Rat-Agtr2-F: 5’-TAACTGCTCACACAAACCGG-3’, Rat-Agtr2-R: 5’-CAAGACTTGGTCACGGGTAA-3’ (Rattus norvegicus angiotensin II receptor, type 2 (Agtr2), NCBI Reference Sequence: NM_012494.3); Gapdh-F5’-CTCTCTGCTCCTCCCTGTTC-3’,Gapdh-R5’-GCCAAATCCGTTCACACCG-3’. (Rattus norvegicus glyceraldehyde-3-phosphate dehydrogenase (Gapdh), NCBI Reference Sequence: NM_017008.4). We used the following RT-PCR protocol: 98°C for 3 minutes initial denaturation followed by 40 cycles of 98°C for 15 seconds and 61°C for 30 minutes.
Statistical Analysis
SPSS 22 program (IBM SPSS Statistics Premium Authorized User V 22) was used for statistical analysis. One-way ANOVA test and Pearson Chi-Square Test were used to evaluate bone total length and area showing ossification (bone length, ossification percentage). For biochemical parameters, the results are presented as mean ± standard deviation of the three replicates. Data in all experiments were analyzed for statistical significance using variance analysis (One-way ANOVA). Post hoc analyzes were performed to compare the parameters of the different groups. Statistical analysis related genetics were performed using REST 2009 V2.0.13 Software.
P less than 0.05 was considered statistically significant. Kruskal Wallis test was used for comparisons between pyramidal cells in the hippocampus CA area. Data were expressed as mean ± standard deviation for each group.
Long bones of the upper and lower extremities (humerus, radius, ulna, femur, tibia and fibula) were evaluated. When 50 mg/kg caffeine was given, there was a significant decrease in ossification and length of ossicles (p <0>
Assessment of Oxidative stress parameters
The highest TAS value obtained at Vitamin E group whereas the highest TOS value obtained at caffeine group. Vitamin E administration increased antioxidant status significantly in caffeine group. Vitamine E showed more antioxidant effect while used without caffeine. TOS values showed that the highest oxidant effect observed at caffeine group. Control group has the lowest TBARS, TOS and OSI values. Oxidative stress index was calculated as ratio of TOS and TAS. OSI was in caffeine group considerably higher than the other groups. OSI decreased in vitamin E administrated groups. In caffeine group SOD and TBARS has highest value compared to the other groups. (Fig. 3-5).
GSH level in humerus is the highest in vitamin E conditions, while in other organs, it is the lowest in caffeine groups. GSSG also has the highest value in the liver in the Caffeine group. Vitamin E increased GSH value while decreased GSSG values comparing Caffeine and control groups respectively (Fig.6). According to these results Vitamin E markedly decreased oxidative stress via stimulating antioxidant system.
IL-1β, IL-6 and TNF-α values were notably higher in caffeine group than in all the other groups (Fig.7).Vitamin E particularly showed an anti-inflammatory effect against caffeine via reducing tissue levels of IL-1β IL-6 and TNF-α. In vitamin E group, the level of Ca2+in the humerus, placenta and liver of the fetuses was found higher than the other groups. In Vitamin E group, Vitamin D value has the highest level (Fig.8).
Pyramidal Cells in the Hippocampus
Average pyramidal cell numbers were calculated for the groups. The average number of pyramidal cells in the control group was found to be 601,231. In previous studies, the average number of pyramidal cells was expressed between 650,000-700,000 and in our study it was slightly less than these results [30, 31]. (Table 4). Possible differences in these measurement results are thought to result from the particle distribution in the Z axis of the tissues in the paraffin block. It is seen that the total number of pyramidal cells in the Caffein group is lower than the control group. There is a statistically significant difference between the control group and other groups (Fig.9).
Placental Gene Expression of Agtr2
The gene expression levels of Agtr2 were significantly increased in the placentas exposed to Vitamin E (p<0>0,05) compared to the controls
Current studies in the literature show that caffeine intake cause toxicological effects especially on the fetus [17]. Cytochrome P450 1A2, the primary enzyme responsible for caffeine metabolism, is not found in both the plesanta and the fetus. This situation causes the metabolic rate of caffeine, which can pass through the plesanta barrier, to be completely dependent on the metabolic capacity of pregnant women and results in the longevity of caffeine [18]. Lamy et al. (2020), in their study, they investigated the caffeine usage of pregnant women and their possible effects on newborns in France and stated that mothers who took at least 100 mg of caffeine per day had shortened birth times. In the study, pregnant rats were administered caffeine and a significantly increased oxidative stress was observed compared to the control group. It is predicted that vitamin E, a powerful antioxidant, will prevent the toxic effect of caffeine in fetal organs [19]. Tomaszewski et al. (2016), in their study, they gave 30 mg/kg caffeine orally to pregnant rats and examined the bone / cartilage ratio of fatuses by the double skeletal staining method. As a result of their studies, they reported that the bone ratio of fetuses exposed to caffeine was lower than the control group [20]. Yılmaz et al. (2018), investigated the protective effects of melatonin against the effects of nicotine on bones in their study; and found that the percentage and rate of ossification was low in the upper and lower extremity bones of the group to which 6 mg/kg nicotine was administered (31.42 ± 10.33) compared to the control group (43.71 ± 2.33). In their study, they stated that this ratio was close to the Control Group in the melatonin group [21]. Goyal et al. (2010), reported that, placental insufficiency is associated with increased expression of many RAS genes. Also, it is reported that, the Agtr2 appears to be re-expressed or up-regulated after vascular injury, myocardial infarction, cardiac failure or wound healing, possibly reflecting re-activation of a foetal genetic programme [22]. The renin-angiotensin system (RAS) in the placenta is a key player in the regulation of maternal-fetal blood flow during pregnancy. It is well known that placental vascular dysfunction negatively affects fetal growth [23]. Angiotensin II is the key effector hormone of the renin–angiotensin system (RAS), causing vasoconstriction, increased afterload, and sodium and fluid retention. All of these actions affect the cardiovascular system and increase blood pressure [24]. Also, AT2 is involved in apoptosis, reduction of endothelial cell growth, cell migration, vasodilation, and reduction of vascular injury [25]. It is reported that the function of the AT2 receptor involved in antiproliferative effects and programmed cell deathAT2 receptor stimulation results in a decrease in MAP kinase activity [26]. The antiproliferative character of the AT2 receptor is reflected in the inhibition of MAP kinase activity [27]. de Gasparo and Siragy, (1999) reported that, Agtr2 is expressed at low density in adult tissues but up-regulated in pathological circumstances and the Angiotensin II receptor plays a role in the pathogenesis and remodeling of cardiovascular and renal diseases [28]. In our study, the results demonstrated that there was an upregulation of mRNA of Angiotensin II receptor expressed in placentas which exposed to E vitamine, caffeine and join effect.
It was determined that there was a decrease in bone development and ossification rate in fetuses of pregnant rats exposed to caffeine. Vitamin E were given to rats against caffeine and it was observed that the ossification increased. Vitamin E supplementation significantly improved anatomical and biochemical and pyramidal cells number findings after caffeine administration and prevented oxidative stress and inflammation. According to these data, we think that vitamin E can be used as a potential therapeutic agent to prevent bone loss induced by caffeine and that our results will be useful in model studies on vitamin E and caffeine.
Data available on request from the authors. The data that support the findings of this study are available from the corresponding author upon reasonable request.
The authorsdeclare no potential conflict of interests.
No funding source was obtained from anywhere in the study, and an experimental study was conducted with our own means.
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.
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.
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 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 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.
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.
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.
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.
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!
"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 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 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 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.
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 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.
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.
“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”.
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.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
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.
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, 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.
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.
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, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
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!”
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
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.
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 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.
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.
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 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.
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 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".
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.
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.
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.
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.
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
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.
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 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 Maria Emerson, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews, Auctores Publishing LLC. I am delighted to have published our manuscript, "Acute Colonic Pseudo-Obstruction (ACPO): A rare but serious complication following caesarean section." I want to thank the editorial team, especially Maria Emerson, for their prompt review of the manuscript, quick responses to queries, and overall support. Yours sincerely Dr. Victor Olagundoye.
Dear Ashley Rosa, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews. Many thanks for publishing this manuscript after I lost confidence the editors were most helpful, more than other journals Best wishes from, Susan Anne Smith, PhD. Australian Breastfeeding Association.
Dear Agrippa Hilda, Editorial Coordinator, Journal of Neuroscience and Neurological Surgery. The entire process including article submission, review, revision, and publication was extremely easy. The journal editor was prompt and helpful, and the reviewers contributed to the quality of the paper. Thank you so much! Eric Nussbaum, MD
Dr Hala Al Shaikh This is to acknowledge that the peer review process for the article ’ A Novel Gnrh1 Gene Mutation in Four Omani Male Siblings, Presentation and Management ’ sent to the International Journal of Clinical Case Reports and Reviews was quick and smooth. The editorial office was prompt with easy communication.
Dear Erin Aust, Editorial Coordinator, Journal of General Medicine and Clinical Practice. We are pleased to share our experience with the “Journal of General Medicine and Clinical Practice”, following the successful publication of our article. The peer review process was thorough and constructive, helping to improve the clarity and quality of the manuscript. We are especially thankful to Ms. Erin Aust, the Editorial Coordinator, for her prompt communication and continuous support throughout the process. Her professionalism ensured a smooth and efficient publication experience. The journal upholds high editorial standards, and we highly recommend it to fellow researchers seeking a credible platform for their work. Best wishes By, Dr. Rakhi Mishra.
