AUCTORES
Globalize your Research
Research Article | DOI: https://doi.org/10.31579/2693-7247/027
1 Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent, Uzbekistan.
2 Institute of Chemistry of Plant Substances, Uzbek Academy of Sciences, Tashkent, Uzbekistan
*Corresponding Author: Mirzayeva Yu.T, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent, Uzbekistan
Citation: Mirzayeva Yu.T. Usmanov P.B. Omonturdiyev S.Z. Ibragimov E.B. and Abrayeva Z.Ch. (2021) Characteristic of the vasorlaxant action of the talatisamine alkaloid and its derivatives J. Pharmaceutics and Pharmacology Research. 4(2); DOI: 10.31579/2693-7247/027
Copyright: © 2021, Mirzayeva Yu.T, 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: 30 December 2020 | Accepted: 04 January 2021 | Published: 02 March 2021
Keywords: aorta, ion channels, receptors, phenylephrine, alkaloids
The aim of our research is to study the effect relaxant action of diterpenoid alkaloids talatisamine, 14-O-benzoylthalatisamine and 14-O-acetylthalatisamine was studied using isolated rat aortic rings. Alkaloids significantly and dose-dependently inhibited contraction of the aortic rings caused by high KCl content. At the same time, under these conditions, alkaloids significantly reduced Ca2+-induced contraction of the aortic rings. The relaxing effects of alkaloids are significantly suppressed by verapamil, a potent potentiometer-dependent Ca2+ channel blocker. The alkaloids also significantly reduced norepinephrine-induced aortic ring contraction in normal as well as Ca2+ free Krebs solutions. The data obtained indicate that talatisamine, 14-benzoylthalatisamine and 14-O-acetylthalatisamine exhibit a pronounced relaxant effect in almost the same way in the case of contraction induced by a high content of KCl and norepinephrine. The mechanism of the relaxant action of alkaloids is probably complex and may include suppression of Ca2+influx through voltage-dependent and receptor-driven Ca2+ channels, as well as inhibition of Ca2+transport in the sarcoplasmic reticulum.
Ca2+ ions play a leading role in ensuring the functional activity of blood vessel SMC. As in heart cells, the contractile activity of SMCs depends on [Ca2+]i, however, the mechanisms involved in its regulation in SMCs have their own characteristics. In this case, the dominant role is also played by potential-dependent Ca2+ -channels of the plasma membrane, the activation of which provides the flow of Ca2+ ions into the cytoplasm of the SMC, the amount of which is sufficient to initiate the contractile process [1]. In addition to voltage-dependent Ca2+ channels, the supply of Ca2+ from the extracellular environment to the SMC is also provided by a supply - detectable and receptor-gated Ca2+ channels, as well as a Na+ / Ca2+ exchanger [2]. In this case, a prerequisite for the activation of stock-operated channels is the depletion of Ca2+ ions in the SR. As the name suggests, the work of receptor-gated Ca2+ channels is controlled by receptors, which interact with specific hormones and mediators to control the work of these channels [3]. At the same time, mediators and hormones activate G proteins through specific receptors, which control the work of various ion channels and enzymes. In particular, in SMCs such activation of phospholipase C is accompanied by the production of inositol 1,4,5-triphosphate (IP3), which interacts with the receptor (IP3R) on the CP membrane, activates the release of Ca2+ and causes an increase in [Ca2+] i in their cytoplasm [4].
We have previously found that the alkaloid 14-O-benzoylthalatizamine (14-O-BT), a derivative of the diterpenoid alkaloid talatizamine isolated from the plant Aconitum talassicum, effectively relaxes the preparations of the aorta, previously contracted by KC1 [5]
Thus, the results of this series of experiments indicate that the modification of the structure of talatizamine by introducing benzoyl or acetyl groups at positions C (14) is accompanied by a significant increase in the relaxant activity of their derivatives (Fig.1) Such an increase in the relaxant activity of talatizamine derivatives is apparently due to an increase in their lipophilicity and, accordingly, membrane activity, which is characteristic of the introduction of aromatic groups (benzoyl and acetyl) into the structure of diterpenoid alkaloids ([6],).
In the course of further characterization of the mechanism underlying the relaxant action of talatizamine and its derivatives, their effects were studied under various experimental conditions.
All animal care and experimental procedures were approved by the Committee for Animal Experiments of Institute of Biophysics and Biochemistry at the National University of Uzbekistan.
After brief anesthesia with sodium pentobarbital, rat was decapitated and the thoracic aorta was isolated. The connective tissue was removed and rings 3 mm long were mounted vertically under isometric conditions in a 5 ml organ bath perfused with Krebs solution containing (in mM): NaCl 118.3, KCl 4.7, CaCl2 2.5, MgSO4 1.2, NaH2PO4 1.2, NaHCO3 25.0, EGTA 1.0 and glucose 11.1 (pH 7.35). Krebs solution was maintained at 37 ± 0.5°C and continuously bubbled with O2/CO2 mixture (95%/5%). An initial load of 1 g was applied and maintained throughout a 60 min equilibration period. During equilibration the bathing solution was changed every 15 min with readjustment of baseline tension, when necessary. Tension was recorded on a pen recorder (Endim 621.02 Germany) via force-displacement transducers (FT03, Grass Instrument, Ma, USA). To assess the participation of the Na+/Ca2+ exchanger in the relaxant action of alkaloids, we studied their effect on the contraction of the rat aortic rings induced by Krebs solution with a low Na+ content. The low-Na+ Krebs solution was obtained by replacing 118 mM of NaCl with iso-osmolar amount of choline chloride. In these experiments after equilibration period in normal Krebs solution the viability of aortic rings was tested by KCl (50mM) or phenylephrine (1 µM). After this procedure, the aortic rings were repeatedly washed with normal Krebs solution, and when the baseline tension was re-established the aortic rings were exposed to low-Na+ Krebs solution containing 10 µM verapamil, and steady contraction was obtained.All reagents were of analytical grade and were obtained from Sigma Chemical Co (St Louis, Mo, USA). All values are expressed as mean ± standard error of mean (S.E.M.). Student’s t test was used for unpaired variants. P<0>
In preliminary experiments, it was found that talatizamine, 14-O-benzoylthalatisamine and 14-O-acetylthalatisamine in a wide range of concentrations did not effect the basal tone of rat aortic preparations. However, in further experiments, we found that the studied alkaloids effectively relax the rat aorta preparations, previously contracted with 50 mM KCl, i.e., they have a relaxing effect. At the same time, the relaxing effect was more pronounced in 14-O-benzoylthalatisamine and 14-O-acetylthalatisamine began to manifest itself already at its concentration of 10 μM and 15 μM, while the relaxant effect of talatizamine was less pronounced and was manifested only at its concentration of 50 μM. The relaxant effect of alkaloids was dose-dependent, and with an increase in their concentration in the range of 10-250 μM, the contraction force of the rat aorta preparation induced by 50 mM KCl decreased from 28.12.2 to 933.4% (Fig.1). The IC50 value, the concentration at which 14-O-benzoylthalatisamine and 14-O-acetyltalatisamin relaxed the aorta preparation by 50%, was 79.5 μM and 98.9 μM, respectively. In contrast to 14-O-BT and 14-O-AT, the dependence of the relaxant effect of talatizamine on its concentration was less pronounced, and the maximum relaxation of the aorta preparation to 42.82.5% was observed at a concentration of 750 μM (Figure 1).
Concentration-response curves to alkaloids were determined in rat aortic rings pre-contracted with KCl (50 mM;). Data are expressed as a percentage of the contraction induced by KCl (50 mM). Values are mean ± SEM (n=6). *P < 0>
Considering that the KCl-induced contraction of the rat aorta is mainly provided by the activation of voltage-dependent Ca2+ channels of the plasmolemma of the SMC and Ca2+ ions coming through them, it can be assumed that the observed relaxant effect of talatizamine, 14-O-BT and 14-O-AT are possibly realized as a result of blocking these channels by them. At the same time, by blocking these channels and suppressing the entry of Ca2+ ions into the SMC, the studied alkaloids, apparently, cause a decrease in the intracellular level of Ca2+ ions, which leads to relaxation of the rat aorta preparations. To test this assumption, we studied the dependence of the relaxant action of the studied alkaloids on the concentration of Ca2+ ions in the incubation medium.
It is known that in solutions containing no Ca2+ ions, hyperpotassium solutions do not cause contractions of aortic preparations, and the cumulative addition of Ca2+ ions under these conditions is accompanied by the development of contractions that reach the control amplitude at 2.5 mM CaCl2 [7]. We found that during incubation of rat aorta preparations in calcium-free Krebs solutions in the presence of 14-O-BT and 50 mM KCl, the addition of Ca2+ ions also stimulated the development of contractile responses, which, however, were significantly less in amplitude than the responses, registered in the control in the absence of 14-О-BT (Fig. 2).
In particular, in the presence of 250 μM 14-O-BT and 14-O-AT, the addition of 2.5 mM CaCl2 to the calcium-free solution caused a contraction of the aorta preparation, which was 83.8±3.9% and 70.8±4.2%, less reduction recorded in the absence of alkaloids. Under similar experimental conditions, in the presence of talatizamine (250 μM), the addition of 2.5 mM CaCl2 caused a contraction, which was 48±4.1% less in amplitude compared to the contraction in the control without alkaloid (Fig. 2). The results of these experiments convincingly indicate that the relaxant effect of the studied alkaloids under conditions of KCl-induced contracture is associated with the suppression of the transport of Ca2+ ions from the extracellular medium into the cytoplasm of the SMC through the voltage-dependent Ca2+-channels of the plasma membrane.
The force of contraction of the rat aorta preparation induced by 50 mM KCl was taken as 100%. Values are mean ± SEM (n=6). *P < 0>
In order to clarify the participation of L-type Ca2+-channels in providing the relaxant action of talatizamine, 14-O-BT and 14-O-AT, the effect of the blocker of these channels verapamil (Ver) on their effects was studied. In these experiments, it was found that in the presence of 0.1 μM (Ver), a concentration corresponding to its IC50, the studied alkaloids retained the ability to suppress KCl-induced contractions of the aorta, but to a lesser extent than in its absence. At the same time, 14-O-BT (250 μM) and 14-O-AT (250 μM) additionally suppressed the strength of the aorta contractions induced by KCl, to 31.5±3.7% and 33.1±4.1% of the control, respectively (Fig. 3,). From these results, it follows that the relaxant action of 14-О-BT and 14-О-АТ alkaloids may be based on the blockade of L-type Ca2+-channels. However, the retention of the relaxant effect of the studied alkaloids in the presence of VP indicates that, along with the blockade of L-type Ca2+-channels, other mechanisms of Ca2+ ion transport into the SMC can be involved in its provision.
In contrast to 14-O-BT and 14-O-AT, the addition of talatizamine (750 μM) under similar conditions did not lead to additional relaxation of the rat aorta preparation.
An important role in the regulation of Ca2+ homeostasis in SMC, along with voltage-dependent Ca2+ channels of the L-type, is also played by receptor-gated Ca2+ channels, which are activated upon stimulation of α-adrenergic receptors [8]. In this regard, to assess the effect of the studied alkaloids on receptor-gated Ca2+ channels, we studied their effects on the contractions of aortic preparations induced by the α-adrenergic receptor
agonist phenylephrine (PE). PE induces contractions of the aorta, which, in the presence of verapamil, are mainly provided by Ca2+ ions entering the SMC through receptor-gated Ca2+ channels [9]. In our experiments, PE (1 μM) in the presence of verapamil (0.1 μM) induced aortic contractions, the force of which was 10.9±2.3% less than the force of contractions caused by it in the absence of verapamil. The addition of alkaloids 14-О-BT and 14-О-AT under these conditions led to a significant suppression of the strength of PE-induced contractions of the aorta, which decreased by 68.4±3.1% and 63.6±3.3% of the control. respectively (Figure 4, A).
A. dose-dependent effect of 14-O-BT and 14-O-AT on rat aortic contractions induced by 1 μM PE in the presence of 0.1 μM verapamil. On the ordinate, the force of aortic contraction, expressed as a percentage of the force induced by 1 μM PE in the absence of verapamil and taken as 100%. The abscissa is the concentration of alkaloids. B. - the effect of phentolamine (10 μM) on the relaxant effect of 14-O-BT and 14-O-AT (* p <0 xss=removed>
The IC50 values obtained for 14-O-BT and 14-O-AT were 80.6 μM and 128 μM, respectively. These results indicate that the observed effect of the studied alkaloids may be due to the blockade of receptor-gated Ca2+-channels. This is confirmed by experiments with a blocker of α-adrenergic receptors - phentolamine, in the presence of which the effects of alkaloids 14-О-BT and 14-О-АТ on PE-induced aortic contractions decreased by 44.7±4.0% and 48.7±4.3%, respectively, from the control obtained in the absence of phentolamine (Fig. 4,B). These results indicate that the blockade of receptor-gated Ca2+-channels may also be involved in providing the relaxant effect of the studied alkaloids. At the same time, an important role in the regulation of the contractile activity of smooth muscles by the α-adrenergic receptor is also played by the Na+/Ca2+ exchange of the plasma membrane of the SMC [10].
It was found that the alkaloids 14-O-BT and 14-O-AT significantly suppress the force of aortic contraction induced by a Na+-free solution in the presence of which it decreased to 28.3±3.6% and 30.1±4.1% of control, respectively (Fig.5. A,B). The IC50 values obtained from the results of these experiments were for 14-O-BT and 14-O-AT, 82.3 μM and 107.8 μM, respectively.
These data indicate that the alkaloids 14-О-BT and 14-О-АТ effectively suppress the contractions of the aorta induced by the Na+ free solution, which are provided by Ca2+ ions entering the SMC through the Na+/Ca2+ exchanger.
Does not contain Na+ ions. A, B - dose-dependent effect of 14-O-BT and 14-O-AT on rat aortic contractions induced by Krebs solution without Na+ ions. On the ordinate axis, the force of aortic contraction, expressed as a percentage of the force induced without Na+ solution and taken as 100%. The abscissa is the concentration of alkaloids. B- Influence of KB-R7943 (10 μM) on the relaxant effect of 14-O-BT and 14-O-AT (* p <0 xss=removed>
This is confirmed in experiments with KB-R7943 blocker of the Na+/Ca2+ exchanger, in the presence of which the effects of 14-O-BT and 14-O-AT alkaloids on aortic contractions induced by Na+-free solution decreased to 46.3±4.2% and 49.4±4.5% of the control obtained in the absence of KB-R7943, respectively (Fig. 5, C).
Analysis of the results of these experiments showed that the alkaloids 14-O-BT and 14-O-AT equally effectively suppress the contractions of the aorta induced by the no-Na+ solution, as evidenced by their close IC50 values. The close IC50 values obtained using two different methods of activation of aortic contractions, which are mainly provided by Ca2+ ions coming through the Na+/Ca2+ exchanger, are convincing evidence of the involvement of this mechanism in providing the relaxant action of 14-O-BT and 14-O-AT. The data obtained in this series of experiments allow us to conclude that, in providing the relaxant effect of alkaloids 14-О-BT and 14-О-АТ, along with the blockade of voltage-dependent Ca2+-channels of the L-type and receptor-gated Ca2+-channels, an important the blockade of the Na+/Ca2+ exchanger of the SMC may also play a role.
This work was supported by a grant ФА-Ф-6-004 from the Coordinating Committee for Development of Science and Technology under the Cabinet of Ministers of the Republic of Uzbekistan.
The authors have declared that no conflict of interest exists.
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.
