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Review Article | DOI: https://doi.org/10.31579/2693-7247/233
Department of Pharmacology, School of pharmacy, RK University Rajkot, India.
*Corresponding Author: Kiran Dudhat, Department of Pharmacology, School of pharmacy, RK University Rajkot, India.
Citation: Chinmyee Saha, Ishita Zalavadiya, Kiran Dudhat, (2025), Apoptosis: A Symphony of Cellular Self-Destruction on Development and Disease, J. Pharmaceutics and Pharmacology Research, 8(3); DOI:10.31579/2693-7247/233
Copyright: © 2025, Kiran Dudhat. 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 May 2025 | Accepted: 19 May 2025 | Published: 30 May 2025
Keywords: dna damage; biological process; early stages; apoptosis; infection; immune response; normal development; cell death; cancer
Apoptosis is a biological process that spontaneously removes unwanted cells from an organism during its early stages of development. It is triggered by several mechanisms, including as endoplasmic reticulum-mediated, mitochondrial-initiated, and extrinsic or cell surface death receptor mediated. Apoptosis can happen in pathological and physiological circumstances & as a result of infections, damaging stimuli, misfolded proteins, and DNA damage. It is necessary for the body to operate correctly and can be brought on by host immunological reactions or infections. Phagocytosis, DNA fragmentation, and protein digestion are all components of apoptosis biochemistry. This article provides an overview of apoptosis, a highly regulated cell death process that plays a crucial role in normal development, tissue homeostasis, and immune response. The article first defines apoptosis and discusses its importance in various physiological and pathological contexts. It then describes the different types of apoptosis, including intrinsic and extrinsic pathways, highlighting their specific mechanisms of activation and execution. The article also explores the intricate network of signalling molecules, such as caspases, Bcl-2 family proteins, and death receptors, that regulate apoptosis. Overall, this article aims to provide a comprehensive understanding of the intricate mechanisms and potential therapeutic approaches related to apoptosis.
Apoptosis serves several important functions in the body. It is involved in embryonic development, helping to shape organs and structures by eliminating excessive or unnecessary cells. It is also crucial for maintaining tissue homeostasis, as it helps to remove damaged or abnormal cells that could potentially harm the overall tissue or organism. Additionally, apoptosis plays a role in the immune system, eliminating infected or cancerous cells, and in the regulation of cell populations in various physiological processes. Dysregulation of apoptosis can have serious consequences and is associated with numerous diseases. Insufficient apoptosis can result in uncontrolled cell growth and contribute to the development of cancer. On the other hand, excessive apoptosis can lead to degenerative diseases characterized by excessive cell death, such as neurodegenerative disorders. In summary, apoptosis is a highly regulated process that plays a essential role in maintaining the health and proper functioning of multicellular organisms. By eliminating damaged or harmful cells, apoptosis ensures the overall well-being and integrity of tissues and organs.
Apoptosis is a natural biological process that occurs in all multicellular organisms, including plants and animals, to remove unwanted cells from the body. It plays a crucial role in human development and maintaining a healthy immune system. On average, 50-80 billion cells die daily in a human adult due to apoptosis, eliminating infected, pre-cancerous, and cancer cells, and maintaining cell balance. [1,2]

Figure 1: Apoptosis Process [5]
Induction of Apoptosis:
Extrinsic or cell surface death receptor mediated pathway. Mitochondrial –initiated pathway(intrinsic). Endoplasmic reticulum (intrinsic) [3]
Morphology of Apoptosis:
Shrinkage of cells. The most defining property is chromatin condensation. Development of apoptotic structures and cytoplasmic blebs. Macrophages' phagocytosis of apoptotic cells or cell bodies. The plasma membrane is unbroken until the very end. Inflammation is not induced by apoptosis [4]
4.1Apoptosis in Physiological situations:
Apoptosis occurs in physiological situations, including development and embryogenesis, endometrial cell loss, nursing breast regression, intestinal crypt epithelia, lymphocytes and neutrophils, and cytotoxic T-cell-induced cell death. It is necessary for normal cell and tissue formation, hormone-dependent tissue, and defense against viruses and tumors.[6]

Figure 2: Physiological Apoptosis [7]
4.2Apoptosis Pathologic Conditions:
DNA damage:
Radiation, cytotoxic medications, temperature extremes, and hypoxia can damage DNA, leading to necrotic cell death. If repair mechanisms fail, cell apoptosis may occur, potentially causing malignant transformation, requiring cell elimination. [6]
Accumulation of Misfolded Protein:
Improperly folded proteins can arise from mutations in the genes encoding these proteins or from extrinsic factors such as free radical damage. Excessive accumulation of these proteins in the ER causes a condition known as ER stress, which culminates in apoptosis of cells. [6]
Cell Injury in certain Infections, particularly Viral Infections:
• Loss of infected cells is largely due to apoptotic death • That may be induced by the virus (As in Adenovirus & Human Immunodeficiency virus infections) • Or By the host Immune response (as in Viral Hepatitis) [6]
Protein Digestion (Caspases):
Protein-protein cross-linking, cytoskeletal protein proteolysis, DNA breakdown, nuclear chromatin fragmentation, and phagocytosis are key processes in apoptosis, allowing macrophages to recognize and initiate inflammatory cell responses. [7]
Steps involved in the programmed cell death:
Enzymes in cells consume proteins, rounding the cell, splitting DNA, and contracting the nuclear membrane, leading to apoptosis and the degeneration of the cell's nuclear membrane.[7]
Cells undergo intrinsic apoptotic pathway when exposed to stressors like low oxygen levels, elevated ROS, or DNA damage. This leads to the cleavage of initiator caspases in mitochondria and endoplasmic reticulum, activating downstream effector caspases, ultimately causing cell death. [8]

Figure 3: Intrinsic pathway of apoptosis [8]
6.2 Extrinsic Pathway:
The binding of a death ligand to a death receptor on the cell membrane initiates the extrinsic pathway of apoptosis. FAS and TNF receptors are death receptors that are triggered by FAS or TNF ligands. Initiator caspases within the cytoplasm are cleaved upon activation of these receptors. Cell death results from this activating downstream effector caspases. [8]

Figure 4: Extrinsic Pathway of Apoptosis [8]
6.3 Steps involved in the programmed cell death:
When the required enzymes begin to function in the cell, they consume the proteins, causing the cell to round out. The DNA inside the nucleus begins to split and finally contracts.The nuclear membrane that surrounds the nucleus of a cell degrades and becomes detached from it when apoptosis begins. [7]
A stands for aspartic acid, and C for cysteine. ASE for the Enzyme-Protease name. A class of proteolytic or protein-splitting enzymes known as caspases function. The key player in the transduction of apoptotic signals is caspases. Two varieties of caspases exist: 8, 10, 9, 2, and effector caspases caspase [ 3, 7, 6.] When initiator caspases bind to a particular oligometric adaptor protein, they become active. These initiator caspases then cleave proteins to activate effector caspases. The cell death program is then carried out.[8]
The apoptosis consists of 3 steps:
8.1 Initiation of Apoptosis:
Apoptosis Including Factor (AIF) triggers apoptosis by acting either extracellularly or intracellularly on the cell membrane, thereby initiating the intrinsic and extrinsic pathways. The AIF are as follows:
Retraction of signals necessary for regular cell survival (e.g., lack of growth hormone, cytokines) Retraction of extracellular signals: FAS receptor activation associated with TNF-R family. Intracellular Stimuli: primarily DNA damage, heat, radiation, and hypoxia. [9]
8.2 Process of Programmed cell death:
Once the cell switched on to self-destruct mode, the programme in-built in the cell will activated:
8.2.1Caspases activation:
Caspases are a class of proteolytic enzymes that act on proteins found in organelles and nuclear proteins. [9]
8.2.2 Death Receptor Activation:
Activation of caspases activates FAS receptor (CD95), a cell surface receptor found on cytotoxic CD8+ T cells that is a member of the TNF-R (tumor necrosis factor receptors) family.
FAS is also referred to as the "death receptor" because it activates particular growth-regulating genes, such as Bcl-2 and P52, when it comes into contact with a particular AIF. (Thus, the Death receptor pathway is the one that develops from FAS activation.). [9]
8.2.3 Activation of Development Regulating pathways of gene/cell death: Pathway of Death Receptor (Extrinsic Pathway):
o TNF-R and CD95 members' stimulation, which further activates caspase 8. Caspases 3 and the effector stage of apoptosis are triggered by this.
Mitochondrial pathway (Intrinsic Pathway):
Triggered by endogenous factors like DNA damage, which subsequently leads to p53 protein transcription and activation of the Bcl-2 gene family (found in the outer membrane of mitochondria). Bcl-2 contains both pro-apoptic members (like BASX, BAK, and BAD) and inhibitors of apoptosis (like BCL-XL), which prevent apoptosis from occurring. The final step involves the release of mitochondrial cytochrome C, which then combines with protein Apaf-1 to form an Apoptosome.
This combination of proteins—Procaspase 9, cytochrome C, and Apoptotic protease act6ivating factor -1—activates caspase 9, which in turn activates caspase 3 and starts the effect stage of apoptosis. P53 has the ability to induce apoptosis in itself. [9]
Cell Death (Effector Stage):
Degradation of the cytoskeleton, disruption of the endoplasmic reticulum, disruption of the nucleus, mitochondrial damage, and disruption of the cell membrane will all occur.
8.3 Phagocytosis:
The dead apoptotic cells develop membrane changes which promote their phagocytosis. Phosphatidylserine & Thrombospondin molecules will appear on the outer surface of the cells in apoptosis which facilitate their identification by adjacent phagocytes. So, it will not initiate any inflammatory response. [19]
It aids in keeping multicellular organisms' homeostasis intact. Apoptosis keeps the body at the appropriate size.
In an organism, apoptosis keeps the number of cells constant. The process of apoptosis rids the body of the undesirable cells. Apoptosis eliminates the harmful T-lymphocytes. Cell development depends on programmed cell death. [10]
Apoptosis is the cause of the fingers splitting apart during fetal development. The dorsal portion of the neural tube closes as a result. The immune system depends on apoptosis, which is crucial for immune response regulation, immune cell recognition of self-antigen elimination, and cytotoxic killing. Cell death eliminates the Wolffian ducts during the fetal sex determination process. Apoptosis in the uterus permits the excision of tissues unnecessary to the bladder and umbilicus. [10]
11.1 Faulty routes
There are numerous distinct biochemical components found in the various forms of apoptotic pathways, many of which are still unknown.[11]
Altering apoptotic pathways can cause diseases or disorders, as seen in lung cancer NCI-H460. While discussing every disease caused by altered pathways is impractical, the general idea remains. [12]
The H460 cell line overexpresses X-linked inhibitor of apoptosis protein (XIAP), reducing proapoptotic agonists and causing cells to proliferate. Abnormalities in apoptosis regulation in cancer cells, such as NF-κB, alter transcriptional regulation and response to apoptotic signals, potentially facilitating cancer spread..[13]
11.1.1 Dysregulation of p53
Dysregulation of p53, a tumor-suppressor protein, can lead to cancer cell apoptosis and impaired apoptosis.[13] This is triggered by alpha- and beta-interferons, which stimulate p53 gene transcription and increase protein levels. Interference with p53 or interferon genes can cause tumor formation.[14])
11.1.2` Inhibition
Inhibition of apoptosis can lead to various cancers, inflammatory illnesses, and viral infections. Cell accumulation is caused by decreased cell death, not increasing cellular proliferation. Cancer is a common example, characterized by overexpression of IAP family members and mutations in cycle-regulating genes, causing abnormal cell responses to apoptosis. [15]. The "Warburg hypothesis" suggests a link between cancer cell apoptosis pathological inactivation and frequent respiratory metabolic shifts towards glycolysis. [16]
11.2 HeLa cell
HeLa cells produce inhibitory proteins that target tumor-suppressive proteins in retinoblastoma. [36] These proteins, expressed by the human papillomavirus (HPV), cause cervical tumors. [18,19]. HPV E6 and E7 disrupt p53, causing cell cycle regulator p53 to become dormant, and preventing apoptosis, thereby preserving HeLa cell immortality [20].
11.2.1Treatments
MiCK test
The MiCK test is a tool used to assess the susceptibility of diseased cells to apoptosis, which is the main treatment strategy for signaling-related diseases. Therapies can increase or decrease apoptosis susceptibility, depending on the cause. Examples include increasing death receptor ligands, blocking anti-apoptotic pathways, and introducing Smac mimetics.[21] Apoptosis is a multi-step process in the body, and cancer treatment primarily targets cells through apoptosis.[22].
11.3 Hyperactive apoptosis
However, loss of control over cell death (excess apoptosis) can result in tissue damage, hematologic disorders, and neurodegenerative diseases. In neurodegenerative diseases like Alzheimer's and Parkinson's, neurons that depend on mitochondrial respiration die a phenomenon called the "Inverse Warburg hypothesis"[23][25]. Moreover, eurodegenerative illnesses and cancer have an inverse epidemiological comorbidity [24]. Excessive apoptosis in HIV-positive patients is linked to abnormal signaling pathways controlling the Bcl-2 family of proteins. This leads to increased expression of apoptotic proteins like BIM, resulting in cell death and various pathologies. Cancer cells can evade apoptosis by inhibiting BIM expression or increasing proteolysis, thereby affecting the progression of HIV.
11.3.1Treatments
HIV progression
HIV progression into AIDS is primarily due to the rapid depletion of CD4+ T-helper lymphocytes, leading to a compromised immune system[26]]. Apoptosis is a key mechanism, triggered by various biochemical pathways. HIV enzymes make cells anti-apoptotic, preparing them for apoptosis [29]. HIV proteins reduce the CD4 glycoprotein marker on cell membranes, and viral particles can cause "bystander" T helper cells to undergo apoptosis.[27]
Researchers from Kumamoto University have developed a new method called "Lock-in and apoptosis" to eradicate HIV in viral reservoir cells. However, this approach is not yet available to HIV patients, as further research is needed to combine existing drug therapy with this approach[28].
11.4Viral infection
A virus infects living cells, causing apoptosis through viral induction, which is crucial for normal cell development, cycle maturation, and maintaining cell operations.
•Viral infections can cause infected cells to undergo apoptosis through a variety of mechanisms, such as:
Binding of receptors
Protein kinase R (PKR) activation;
11.4.1 P53 interaction
The canine distemper virus (CDV) induces apoptosis in both in vivo and in vitro central nervous systems and lymphoid tissue of infected dogs through the extrinsic pathway, which triggers caspases that impair cellular function and ultimately result in cell death [30,31]. The Oropouche virus (OROV) is a zoonotic arbovirus that disrupts cultured cells, such as HeLa cells, and requires viral uncoating, viral internalization, and cell replication. Proteins that can prevent apoptosis are encoded by numerous viruses, such as Bcl-2 homologs, caspase inhibitors, and p53 inhibitors [32]. These proteins bind to p53 and prevent its transcriptional transactivation activity, preventing the production of proapoptotic protein [33]. s However, viruses can survive apoptosis, especially in the latter phases of infection, as phagocytes consume apoptotic bodies that separate from the dying cell's surface, preventing the host response from starting and encouraging the infection to propagate. Neurons may also undergo apoptosis due to prions[34,35].
Apoptosis in OROV requires viral uncoating, internalisation, and cell replication. Some viruses respond to external stimuli, while others activate it via intracellular cues and mitochondria[33]. Many viruses encode proteins that prevent apoptosis, such as Bcl-2 homologs, caspase inhibitors, and p53 inhibitors[36,37]. These proteins block proapoptotic proteins, such as BAK and BAX, and prevent TNF and Fas from triggering reactions[38]. Viruses can survive apoptosis, especially in the latter phases of infection, by exporting apoptotic bodies and phagocytes. Neurons may also undergo apoptosis due to prions. [39]
11.5 Plants
Caspase inhibitors enable the assessment of biological processes containing active caspases. In the absence of caspase activation, cells can still have apoptotic morphology. This behavior is linked to mitochondrial release of AIF and its NLS-mediated translocation into the nucleus. [40]
In conclusion, apoptosis is a highly regulated and crucial process in maintaining cellular balance and homeostasis. It plays a fundamental role in embryonic development, tissue remodelling, and immune system regulation. Through various signalling pathways and cellular mechanisms, apoptosis ensures the removal of unwanted or damaged cells, preventing the accumulation of potentially harmful substances, in this article Intrinsic & Extrinsic pathway are also explained details with proper figures. This article is involves with the discussion of cause, biochemistry, types, significance, role, implication in disease of apoptosis. Besides this, apoptosis acts as a defense mechanism against the development of cancer, as it eliminates cells with DNA damage or unrestrained proliferation. The dysregulation of apoptosis can lead to severe health implications, such as autoimmune diseases, neurodegenerative disorders, and cancer. Thus, a comprehensive understanding of the apoptotic process is essential for therapeutic advancements and medical interventions aimed at modulating cell death to alleviate diseases. Further research into apoptosis and its intricate mechanisms holds promise for improved treatments and potential breakthroughs in combating various illnesses.
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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.
Dear Jessica Magne, Editorial Coordinator, Clinical Cardiology and Cardiovascular Interventions, Auctores Publishing LLC. The peer review process of the journal of Clinical Cardiology and Cardiovascular Interventions was excellent and fast, as was the support of the editorial office and the quality of the journal. Kind regards Walter F. Riesen Prof. Dr. Dr. h.c. Walter F. Riesen.
Dear Ashley Rosa, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews, Auctores Publishing LLC. Thank you for publishing our article, Exploring Clozapine's Efficacy in Managing Aggression: A Multiple Single-Case Study in Forensic Psychiatry in the international journal of clinical case reports and reviews. We found the peer review process very professional and efficient. The comments were constructive, and the whole process was efficient. On behalf of the co-authors, I would like to thank you for publishing this article. With regards, Dr. Jelle R. Lettinga.
Dear Clarissa Eric, Editorial Coordinator, Journal of Clinical Case Reports and Studies, I would like to express my deep admiration for the exceptional professionalism demonstrated by your journal. I am thoroughly impressed by the speed of the editorial process, the substantive and insightful reviews, and the meticulous preparation of the manuscript for publication. Additionally, I greatly appreciate the courteous and immediate responses from your editorial office to all my inquiries. Best Regards, Dariusz Ziora
Dear Chrystine Mejia, Editorial Coordinator, Journal of Neurodegeneration and Neurorehabilitation, Auctores Publishing LLC, We would like to thank the editorial team for the smooth and high-quality communication leading up to the publication of our article in the Journal of Neurodegeneration and Neurorehabilitation. The reviewers have extensive knowledge in the field, and their relevant questions helped to add value to our publication. Kind regards, Dr. Ravi Shrivastava.
Dear Clarissa Eric, Editorial Coordinator, Journal of Clinical Case Reports and Studies, Auctores Publishing LLC, USA Office: +1-(302)-520-2644. I would like to express my sincere appreciation for the efficient and professional handling of my case report by the ‘Journal of Clinical Case Reports and Studies’. The peer review process was not only fast but also highly constructive—the reviewers’ comments were clear, relevant, and greatly helped me improve the quality and clarity of my manuscript. I also received excellent support from the editorial office throughout the process. Communication was smooth and timely, and I felt well guided at every stage, from submission to publication. The overall quality and rigor of the journal are truly commendable. I am pleased to have published my work with Journal of Clinical Case Reports and Studies, and I look forward to future opportunities for collaboration. Sincerely, Aline Tollet, UCLouvain.
Dear Ms. Mayra Duenas, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews. “The International Journal of Clinical Case Reports and Reviews represented the “ideal house” to share with the research community a first experience with the use of the Simeox device for speech rehabilitation. High scientific reputation and attractive website communication were first determinants for the selection of this Journal, and the following submission process exceeded expectations: fast but highly professional peer review, great support by the editorial office, elegant graphic layout. Exactly what a dynamic research team - also composed by allied professionals - needs!" From, Chiara Beccaluva, PT - Italy.
Dear Maria Emerson, Editorial Coordinator, we have deeply appreciated the professionalism demonstrated by the International Journal of Clinical Case Reports and Reviews. The reviewers have extensive knowledge of our field and have been very efficient and fast in supporting the process. I am really looking forward to further collaboration. Thanks. Best regards, Dr. Claudio Ligresti
Dear Chrystine Mejia, Editorial Coordinator, Journal of Neurodegeneration and Neurorehabilitation. “The peer review process was efficient and constructive, and the editorial office provided excellent communication and support throughout. The journal ensures scientific rigor and high editorial standards, while also offering a smooth and timely publication process. We sincerely appreciate the work of the editorial team in facilitating the dissemination of innovative approaches such as the Bonori Method.” Best regards, Dr. Matteo Bonori.
I recommend without hesitation submitting relevant papers on medical decision making to the International Journal of Clinical Case Reports and Reviews. I am very grateful to the editorial staff. Maria Emerson was a pleasure to communicate with. The time from submission to publication was an extremely short 3 weeks. The editorial staff submitted the paper to three reviewers. Two of the reviewers commented positively on the value of publishing the paper. The editorial staff quickly recognized the third reviewer’s comments as an unjust attempt to reject the paper. I revised the paper as recommended by the first two reviewers.
Dear Maria Emerson, Editorial Coordinator, Journal of Clinical Research and Reports. Thank you for publishing our case report: "Clinical Case of Effective Fetal Stem Cells Treatment in a Patient with Autism Spectrum Disorder" within the "Journal of Clinical Research and Reports" being submitted by the team of EmCell doctors from Kyiv, Ukraine. We much appreciate a professional and transparent peer-review process from Auctores. All research Doctors are so grateful to your Editorial Office and Auctores Publishing support! I amiably wish our article publication maintained a top quality of your International Scientific Journal. My best wishes for a prosperity of the Journal of Clinical Research and Reports. Hope our scientific relationship and cooperation will remain long lasting. Thank you very much indeed. Kind regards, Dr. Andriy Sinelnyk Cell Therapy Center EmCell
Dear Editorial Team, Clinical Cardiology and Cardiovascular Interventions. It was truly a rewarding experience to work with the journal “Clinical Cardiology and Cardiovascular Interventions”. The peer review process was insightful and encouraging, helping us refine our work to a higher standard. The editorial office offered exceptional support with prompt and thoughtful communication. I highly value the journal’s role in promoting scientific advancement and am honored to be part of it. Best regards, Meng-Jou Lee, MD, Department of Anesthesiology, National Taiwan University Hospital.
Dear Editorial Team, Journal-Clinical Cardiology and Cardiovascular Interventions, “Publishing my article with Clinical Cardiology and Cardiovascular Interventions has been a highly positive experience. The peer-review process was rigorous yet supportive, offering valuable feedback that strengthened my work. The editorial team demonstrated exceptional professionalism, prompt communication, and a genuine commitment to maintaining the highest scientific standards. I am very pleased with the publication quality and proud to be associated with such a reputable journal.” Warm regards, Dr. Mahmoud Kamal Moustafa Ahmed
Dear Maria Emerson, Editorial Coordinator of ‘International Journal of Clinical Case Reports and Reviews’, I appreciate the opportunity to publish my article with your journal. The editorial office provided clear communication during the submission and review process, and I found the overall experience professional and constructive. Best regards, Elena Salvatore.
Dear Mayra Duenas, Editorial Coordinator of ‘International Journal of Clinical Case Reports and Reviews Herewith I confirm an optimal peer review process and a great support of the editorial office of the present journal
Dear Editorial Team, Clinical Cardiology and Cardiovascular Interventions. I am really grateful for the peers review; their feedback gave me the opportunity to reflect on the message and impact of my work and to ameliorate the article. The editors did a great job in addition by encouraging me to continue with the process of publishing.
Dear Cecilia Lilly, Editorial Coordinator, Endocrinology and Disorders, Thank you so much for your quick response regarding reviewing and all process till publishing our manuscript entitled: Prevalence of Pre-Diabetes and its Associated Risk Factors Among Nile College Students, Sudan. Best regards, Dr Mamoun Magzoub.
International Journal of Clinical Case Reports and Reviews is a high quality journal that has a clear and concise submission process. The peer review process was comprehensive and constructive. Support from the editorial office was excellent, since the administrative staff were responsive. The journal provides a fast and timely publication timeline.
Dear Maria Emerson, Editorial Coordinator of International Journal of Clinical Case Reports and Reviews, What distinguishes International Journal of Clinical Case Report and Review is not only the scientific rigor of its publications, but the intellectual climate in which research is evaluated. The submission process is refreshingly free of unnecessary formal barriers and bureaucratic rituals that often complicate academic publishing without adding real value. The peer-review system is demanding yet constructive, guided by genuine scientific dialogue rather than hierarchical or authoritarian attitudes. Reviewers act as collaborators in improving the manuscript, not as gatekeepers imposing arbitrary standards. This journal offers a rare balance: high methodological standards combined with a respectful, transparent, and supportive editorial approach. In an era where publishing can feel more burdensome than research itself, this platform restores the original purpose of peer review — to refine ideas, not to obstruct them Prof. Perlat Kapisyzi, FCCP PULMONOLOGIST AND THORACIC IMAGING.
Dear Grace Pierce, International Journal of Clinical Case Reports and Reviews I appreciate the opportunity to review for Auctore Journal, as the overall editorial process was smooth, transparent and professionally managed. This journal maintains high scientific standards and ensures timely communications with authors, which is truly commendable. I would like to express my special thanks to editor Grace Pierce for his constant guidance, promt responses, and supportive coordination throughout the review process. I am also greatful to Eleanor Bailey from the finance department for her clear communication and efficient handling of all administrative matters. Overall, my experience with Auctore Journal has been highly positive and rewarding. Best regards, Sabita sinha
Dear Mayra Duenas, Editorial Coordinator of the journal IJCCR, I write here a little on my experience as an author submitting to the International Journal of Clinical Case Reports and Reviews (IJCCR). This was my first submission to IJCCR and my manuscript was inherently an outsider’s effort. It attempted to broadly identify and then make some sense of life’s under-appreciated mysteries. I initially had responded to a request for possible submissions. I then contacted IJCCR with a tentative topic for a manuscript. They quickly got back with an approval for the submission, but with a particular requirement that it be medically relevant. I then put together a manuscript and submitted it. After the usual back-and-forth over forms and formality, the manuscript was sent off for reviews. Within 2 weeks I got back 4 reviews which were both helpful and also surprising. Surprising in that the topic was somewhat foreign to medical literature. My subsequent updates in response to the reviewer comments went smoothly and in short order I had a series of proofs to evaluate. All in all, the whole publication process seemed outstanding. It was both helpful in terms of the paper’s content and also in terms of its efficient and friendly communications. Thank you all very much. Sincerely, Ted Christopher, Rochester, NY.