Journal Description
Pathophysiology
Pathophysiology
is an international, peer-reviewed, open access journal on the etiology, development, and elimination of pathological processes. Pathophysiology is the official journal of the International Society for Pathophysiology (ISP) and is published quarterly online by MDPI (from Volume 27, Issue 1 - 2020).
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within ESCI (Web of Science), Scopus, PMC, PubMed, and other databases.
- Journal Rank: CiteScore - Q2 (Pathology and Forensic Medicine)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 22.6 days after submission; acceptance to publication is undertaken in 3.9 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names published annually in the journal.
Latest Articles
Histologic Analysis of ‘Distraction Vaginogenesis’ in a Rat Model
Pathophysiology 2024, 31(2), 298-308; https://doi.org/10.3390/pathophysiology31020022 - 8 Jun 2024
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Vaginal agenesis (VA) is frequently associated with mullerian agenesis. VA treatments include mechanical dilation and surgical vaginoplasty. We created a vaginal expansion sleeve (VES) as a novel device to progressively lengthen the vaginal canal. This study evaluated the histologic effects of the VES
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Vaginal agenesis (VA) is frequently associated with mullerian agenesis. VA treatments include mechanical dilation and surgical vaginoplasty. We created a vaginal expansion sleeve (VES) as a novel device to progressively lengthen the vaginal canal. This study evaluated the histologic effects of the VES on rat vaginal tissue. The VES is a spring-like device made of proprietary woven cylindrical material and flat resin caps. The VESs were constructed as 25–30 mm, pre-contracted springs, which were secured into the vaginas of six Sprague Dawley rats and allowed to re-expand post-surgically. After one week, the VESs were removed, and the vaginas were harvested and measured in length. Test (n = 6) and control (n = 4) formalin-fixed paraffin-embedded tissues were stained with hematoxylin and eosin (H&E), Masson’s trichrome, and anti-Desmin antibodies. The VESs achieved significant vaginal lengthening. The mean vaginal canal length increased from 20.0 ± 2.4 mm to 23.8 ± 1.2 mm after removal of the VESs (n = 6, p < 0.001), a 19% increase. There was a positive correlation between the expander/tension generated in the vagina and the amount of acute and chronic inflammation. H&E staining revealed increased submucosal eosinophilia in five of the six test tissues. One VES sample that was lengthened to 30 mm long showed evidence of lymphocytic and neutrophilic inflammation. Desmin immunostaining and Masson’s trichrome stain revealed a thinner muscularis with more infiltrative fibrous tissue between muscle fibers in the test tissue compared to the control tissue. Although effective, the VES may provoke at least a transient increase in eosinophils consistent with a localized immune reaction during muscularis remodeling.
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Open AccessReview
Fertility Preservation and Ovarian Hyperstimulation Syndrome Management in Cancer Care: A Pathophysiological Perspective on Gonadotropin-Releasing Hormone Agonists and Antagonists
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Giuliano Bedoschi, Caroline Ingold and Paula Andrea Navarro
Pathophysiology 2024, 31(2), 288-297; https://doi.org/10.3390/pathophysiology31020021 - 7 Jun 2024
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This narrative review delves into the evolving landscape of fertility preservation techniques, with a particular focus on their use in patients undergoing oncology treatment that carries a risk of ovarian insufficiency. Advances in established methods such as cryopreservation of oocytes and embryos are
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This narrative review delves into the evolving landscape of fertility preservation techniques, with a particular focus on their use in patients undergoing oncology treatment that carries a risk of ovarian insufficiency. Advances in established methods such as cryopreservation of oocytes and embryos are highlighted, and the increasing use of gonadotropin-releasing hormone (GnRH) agonists is discussed. The review also addresses the complexities and controversies associated with these approaches, such as the ‘flare-up’ effect associated with GnRH agonists and the potential of GnRH antagonists to reduce the risk of ovarian hyperstimulation syndrome. Despite advances in fertility preservation, the report highlights the challenges we face, including the need for personalized treatment protocols and the management of associated risks. It calls for continued research and collaboration between healthcare professionals to refine these techniques and ultimately improve reproductive outcomes for patients facing the prospect of fertility-impairing treatment.
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Open AccessReview
Bronchial Asthma and COVID-19: Etiology, Pathological Triggers, and Therapeutic Considerations
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Anna Starshinova, Anastasia Borozinets, Anastasia Kulpina, Vitaliy Sereda, Artem Rubinstein, Igor Kudryavtsev and Dmitry Kudlay
Pathophysiology 2024, 31(2), 269-287; https://doi.org/10.3390/pathophysiology31020020 - 27 May 2024
Abstract
Bronchial asthma (BA) continues to be a difficult disease to diagnose. Various factors have been described in the development of BA, but to date, there is no clear evidence for the etiology of this chronic disease. The emergence of COVID-19 has contributed to
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Bronchial asthma (BA) continues to be a difficult disease to diagnose. Various factors have been described in the development of BA, but to date, there is no clear evidence for the etiology of this chronic disease. The emergence of COVID-19 has contributed to the pandemic course of asthma and immunologic features. However, there are no unambiguous data on asthma on the background and after COVID-19. There is correlation between various trigger factors that provoke the development of bronchial asthma. It is now obvious that the SARS-CoV-2 virus is one of the provoking factors. COVID-19 has affected the course of asthma. Currently, there is no clear understanding of whether asthma progresses during or after COVID-19 infection. According to the results of some studies, a significant difference was identified between the development of asthma in people after COVID-19. Mild asthma and moderate asthma do not increase the severity of COVID-19 infection. Nevertheless, oral steroid treatment and hospitalization for severe BA were associated with higher COVID-19 severity. The influence of SARS-CoV-2 infection is one of the protective factors. It causes the development of severe bronchial asthma. The accumulated experience with omalizumab in patients with severe asthma during COVID-19, who received omalizumab during the pandemic, has strongly suggested that continued treatment with omalizumab is safe and may help prevent the severe course of COVID-19. Targeted therapy for asthma with the use of omalizumab may also help to reduce severe asthma associated with COVID-19. However, further studies are needed to prove the effect of omalizumab. Data analysis should persist, based on the results of the course of asthma after COVID-19 with varying degrees of severity.
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(This article belongs to the Collection Feature Papers in Pathophysiology)
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Open AccessReview
Neuromodulation and the Gut–Brain Axis: Therapeutic Mechanisms and Implications for Gastrointestinal and Neurological Disorders
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Baha’ Aljeradat, Danisha Kumar, Sulaiman Abdulmuizz, Mrinmoy Kundu, Yasser F. Almealawy, Dima Ratib Batarseh, Oday Atallah, Michelle Ennabe, Muath Alsarafandi, Albert Alan and Martin Weinand
Pathophysiology 2024, 31(2), 244-268; https://doi.org/10.3390/pathophysiology31020019 - 17 May 2024
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The gut–brain axis (GBA) represents a complex, bidirectional communication network that intricately connects the gastrointestinal tract with the central nervous system (CNS). Understanding and intervening in this axis opens a pathway for therapeutic advancements for neurological and gastrointestinal diseases where the GBA has
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The gut–brain axis (GBA) represents a complex, bidirectional communication network that intricately connects the gastrointestinal tract with the central nervous system (CNS). Understanding and intervening in this axis opens a pathway for therapeutic advancements for neurological and gastrointestinal diseases where the GBA has been proposed to play a role in the pathophysiology. In light of this, the current review assesses the effectiveness of neuromodulation techniques in treating neurological and gastrointestinal disorders by modulating the GBA, involving key elements such as gut microbiota, neurotrophic factors, and proinflammatory cytokines. Through a comprehensive literature review encompassing PubMed, Google Scholar, Web of Science, and the Cochrane Library, this research highlights the role played by the GBA in neurological and gastrointestinal diseases, in addition to the impact of neuromodulation on the management of these conditions which include both gastrointestinal (irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and gastroesophageal reflux disease (GERD)) and neurological disorders (Parkinson’s disease (PD), Alzheimer’s disease (AD), autism spectrum disorder (ASD), and neuropsychiatric disorders). Despite existing challenges, the ability of neuromodulation to adjust disrupted neural pathways, alleviate pain, and mitigate inflammation is significant in improving the quality of life for patients, thereby offering exciting prospects for future advancements in patient care.
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Open AccessReview
Biophysical Mechanisms of Vaginal Smooth Muscle Contraction: The Role of the Membrane Potential and Ion Channels
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Chitaranjan Mahapatra and Ravinder Kumar
Pathophysiology 2024, 31(2), 225-243; https://doi.org/10.3390/pathophysiology31020018 - 14 May 2024
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The vagina is an essential component of the female reproductive system and is responsible for providing female sexual satisfaction. Vaginal smooth muscle contraction plays a crucial role in various physiological processes, including sexual arousal, childbirth, and urinary continence. In pathophysiological conditions, such as
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The vagina is an essential component of the female reproductive system and is responsible for providing female sexual satisfaction. Vaginal smooth muscle contraction plays a crucial role in various physiological processes, including sexual arousal, childbirth, and urinary continence. In pathophysiological conditions, such as pelvic floor disorders, aberrations in vaginal smooth muscle function can lead to urinary incontinence and pelvic organ prolapse. A set of cellular and sub-cellular physiological mechanisms regulates the contractile properties of the vaginal smooth muscle cells. Calcium influx is a crucial determinant of smooth muscle contraction, facilitated through voltage-dependent calcium channels and calcium release from intracellular stores. Comprehensive reviews on smooth muscle biophysics are relatively scarce within the scientific literature, likely due to the complexity and specialized nature of the topic. The objective of this review is to provide a comprehensive description of alterations in the cellular physiology of vaginal smooth muscle contraction. The benefit associated with this particular approach is that conducting a comprehensive examination of the cellular mechanisms underlying contractile activation will enable the creation of more targeted therapeutic agents to control vaginal contraction disorders.
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Open AccessArticle
Early and Long-Term Results of Simultaneous and Staged Revascularization of Coronary and Carotid Arteries
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Elena Golukhova, Igor Sigaev, Milena Keren, Inessa Slivneva, Bektur Berdibekov, Nina Sheikina, Olga Kozlova, Valery Arakelyan, Irina Volkovskaya, Tatiana Zavalikhina and Susanna Avakova
Pathophysiology 2024, 31(2), 210-224; https://doi.org/10.3390/pathophysiology31020017 - 13 Apr 2024
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Background: Carotid artery disease is prevalent among patients with coronary heart disease. The concomitant severe lesions in the carotid and coronary arteries may necessitate either simultaneous or staged revascularization involving coronary bypass and carotid endarterectomy. However, there is presently a lack of consensus
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Background: Carotid artery disease is prevalent among patients with coronary heart disease. The concomitant severe lesions in the carotid and coronary arteries may necessitate either simultaneous or staged revascularization involving coronary bypass and carotid endarterectomy. However, there is presently a lack of consensus on the optimal choice of surgical treatment tactics for patients with significant stenoses in both carotid and coronary arteries. The aim of the current study was to compare the 30-day and long-term outcomes of coronary and carotid artery revascularization surgery based on the simultaneous or staged surgical tactics. Material and Methods: This single-center retrospective study involved 192 patients with concurrent coronary artery disease and carotid artery stenosis ≥ 70%, of whom 106 patients underwent simultaneous intervention (CABG + CEA) and 86 patients underwent staged CABG/CEA. The mean time between stages ranged from 1 to 4 months (mean 1.88 ± 0.9 months). The endpoints included death from any cause, non-fatal stroke, non-fatal myocardial infarction (MI), and major adverse cardiovascular events (MACEs) (death + non-fatal MI + non-fatal stroke) within 30 days after the last intervention and in the long-term follow-up period (median follow-up—6 years). Results: The 30-day all-cause mortality, incidence of postoperative non-fatal MI, non-fatal stroke, and MACEs did not exhibit differences between the groups after single-stage and staged interventions. However, the overall risk of postoperative complications (adjusted for the risk of any complication per patient) (OR 2.214, 95% CI 1.048–4.674, p = 0.035), as well as the duration of ventilatory support (p = 0.004), was elevated in the group after simultaneous interventions compared with the staged intervention group. This difference did not result in an increased incidence of death and MACEs in the group after simultaneous interventions. In the long-term follow-up period, there were no significant differences observed when comparing simultaneous or staged surgical tactics in terms of overall survival (54.9% and 62.6% in Groups 1 and 2, respectively, P log-rank = 0.068), non-fatal stroke-free survival (45.6% and 33.6% in Groups 1 and 2, respectively, P log-rank = 0.364), non-fatal MI-survival (57.6% and 73.5% in Groups 1 and 2, respectively, P log-rank = 0.169), and MACE-free survival (7.1% and 30.2% in Groups 1 and 2, respectively, P log-rank = 0.060). The risk factors associated with an unfavorable outcome included age, smoking, BMI, LV EF, and atherosclerosis of the lower extremity arteries. Conclusions: This study revealed no significant difference in the impact of simultaneous CABG + CEA or staged CABG/CEA on the incidence of death, stroke, MI, and MACEs over a 30-day and long-term follow-up period. Although the immediate results indicated an increased risk of a complicated course (attributable to overall complications) and more prolonged ventilation after simultaneous CABG + CEA compared with staged CABG/CEA, this did not lead to an increase in fatal complications. Therefore, the implementation of either tactic is considered eligible and appropriate following a thorough operative risk assessment.
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Open AccessReview
COVID-19-Induced Diabetes Mellitus: Comprehensive Cellular and Molecular Mechanistic Insights
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Praise Tatenda Nhau, Mlindeli Gamede and Ntethelelo Sibiya
Pathophysiology 2024, 31(2), 197-209; https://doi.org/10.3390/pathophysiology31020016 - 8 Apr 2024
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Despite evidence demonstrating the risks of developing diabetes mellitus because of SARS-CoV-2, there is, however, insufficient scientific data available to elucidate the relationship between diabetes mellitus and COVID-19. Research indicates that SARS-CoV-2 infection is associated with persistent damage to organ systems due to
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Despite evidence demonstrating the risks of developing diabetes mellitus because of SARS-CoV-2, there is, however, insufficient scientific data available to elucidate the relationship between diabetes mellitus and COVID-19. Research indicates that SARS-CoV-2 infection is associated with persistent damage to organ systems due to the systemic inflammatory response. Since COVID-19 is known to induce these conditions, further investigation is necessary to fully understand its long-term effects on human health. Consequently, it is essential to consider the effect of the COVID-19 pandemic when predicting the prevalence of diabetes mellitus in the future, especially since the incidence of diabetes mellitus was already on the rise before the pandemic. Additional research is required to fully comprehend the impact of SARS-CoV-2 infection on glucose tolerance and insulin sensitivity. Therefore, this article delves deeper into the current literature and links the perceived relationship between SARS-CoV-2 and diabetes. In addition, the article highlights the necessity for further research to fully grasp the mechanisms that SARS-CoV-2 utilises to induce new-onset diabetes. Where understanding and consensus are reached, therapeutic interventions to prevent the onset of diabetes could be proposed. Lastly, we propose advocating for the regular screening of diabetes and pre-diabetes, particularly for the high-risk population with a history of COVID-19 infection.
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(This article belongs to the Collection Feature Papers in Pathophysiology)
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Open AccessBrief Report
Evaluation of Renal Function with Urinary NGAL and Doppler Ultrasonography in ICU Patients: A 1-Year Observational Pilot Study
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Etrusca Brogi, Rocco Rago and Francesco Forfori
Pathophysiology 2024, 31(2), 190-196; https://doi.org/10.3390/pathophysiology31020015 - 3 Apr 2024
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Background: We estimated the diagnostic accuracy of urinary NGAL for the diagnosis of AKI. Methods: Urinary NGAL and Creatinine were measured daily for up to 3 days. Doppler ultrasonography was performed within 24 h of admission and for the following 3 days. Results:
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Background: We estimated the diagnostic accuracy of urinary NGAL for the diagnosis of AKI. Methods: Urinary NGAL and Creatinine were measured daily for up to 3 days. Doppler ultrasonography was performed within 24 h of admission and for the following 3 days. Results: Of the 21 patients, 44% had AKI during their ICU stay. The AKI group presented with higher values of serum Creatinine, renal length, MDRD as well as SAPS II already at admission. Urinary NGAL was significantly higher among patients with AKI and patients AKI-no at T0 (p < 0.0001) and increased steadily on T1 and T2. Urinary NGAL seemed to be a notable diagnostic marker for AKI from the first measurement (T0) with an area under the ROC of 0.93 (95% CI = 0.78–0.99) with a sensitivity of 99%. RRI levels were slightly higher in the AKI group at each time and increased gradually from T0 to T2 but reached statistical significance only at T2 (p = 0.02). Renal length and SAPS II at T0 showed high AuRoc and sensitivity. Conclusions: Urinary NGAL is a valuable marker for AKI in intensive care settings. It seemed that a pre-existing chronic renal disease, the SAPS II and the NGAL at admission represented the principal predictors of AKI.
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Open AccessArticle
Depth of SCUBA Diving Affects Cardiac Autonomic Nervous System
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Marina Vulić, Branislav Milovanovic, Ante Obad, Duška Glavaš, Igor Glavicic, Damir Zubac, Maja Valic and Zoran Valic
Pathophysiology 2024, 31(2), 183-189; https://doi.org/10.3390/pathophysiology31020014 - 29 Mar 2024
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The present study investigated the influence of SCUBA dives with compressed air at depths of 10 and 20 m on ECG-derived HRV parameters in apparently healthy individuals. We hypothesized that cardiac sympathetic activity (measured by HRV parameters) adapts proportionally to diving depth, and
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The present study investigated the influence of SCUBA dives with compressed air at depths of 10 and 20 m on ECG-derived HRV parameters in apparently healthy individuals. We hypothesized that cardiac sympathetic activity (measured by HRV parameters) adapts proportionally to diving depth, and that both time- and frequency-domain parameters are sensitive enough to track changes in cardiac ANS function during diving activities and subsequently during the recovery period. Eleven healthy middle-aged recreational divers (nine men and two women, age 43 ± 8, all nonsmokers) volunteered to participate in the present study. The participants (all open-circuit divers) were equipped with dry suits and ECG Holter devices and were later randomly assigned to dive pairs and depths (10 m vs. 20 m), and each participant served as his or her own control. No interaction effects (diving depth x time epoch) were found for the most commonly used HRV markers. More precisely, in response to two different diving protocols, a significant post hoc effect of time was observed for HR and SDNN, as these parameters transiently decreased during the dives and returned to baseline after ascent (p < 0.001). The ULF, VLF (p < 0.003), TP, and LF parameters decreased significantly during the dives, while HF significantly increased (p < 0.003). SCUBA diving apparently challenges the cardiac ANS, even in healthy individuals. The observed changes reveal possible underwater methods of influencing the parasympathetic activity of the heart depending on the depth of the dive. These results identify autonomic nervous system markers to track the cardiovascular risk related to diving and point to the possibility of tracking cardiovascular system benefits during underwater activities in selected patients.
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Open AccessArticle
A Multiomics Assessment of Preoperative Exercise in Pancreatic Cancer Survivors Receiving Neoadjuvant Therapy: A Case Series
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Travis Nemkov, Francesca Cendali, Monika Dzieciatkowska, Daniel Stephenson, Kirk C. Hansen, Catherine M. Jankowski, Angelo D’Alessandro and Ryan J. Marker
Pathophysiology 2024, 31(1), 166-182; https://doi.org/10.3390/pathophysiology31010013 - 20 Mar 2024
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To molecularly characterize the impact of exercise on mitigating neoadjuvant treatment (NAT)-induced physical decline in pancreatic ductal adenocarcinoma (PDAC) patients, a multi-omics approach was employed for the analysis of plasma samples before and after a personalized exercise intervention. Consisting of personalized aerobic and
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To molecularly characterize the impact of exercise on mitigating neoadjuvant treatment (NAT)-induced physical decline in pancreatic ductal adenocarcinoma (PDAC) patients, a multi-omics approach was employed for the analysis of plasma samples before and after a personalized exercise intervention. Consisting of personalized aerobic and resistance exercises, this intervention was associated with significant molecular changes that correlated with improvements in lean mass, appendicular skeletal muscle index (ASMI), and performance in the 400-m walk test (MWT) and sit-to-stand test. These alterations indicated exercise-induced modulation of inflammation and mitochondrial function markers. This case study provides proof-of-principal application for multiomics-based assessments of supervised exercise, thereby supporting this intervention as a feasible and beneficial intervention for PDAC patients to potentially enhance treatment response and patient quality of life. The molecular changes observed here underscore the importance of physical activity in cancer treatment protocols, advocating for the development of accessible multiomics-guided exercise programs for cancer patients.
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Open AccessArticle
Differential Effect of Chronic Morphine on Neuronal Degeneration in Male vs. Female Mice
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Chet Brazile, Jr., Ruping Fan, Beau Benoit, Thomas Arnold and Nadejda Korneeva
Pathophysiology 2024, 31(1), 152-165; https://doi.org/10.3390/pathophysiology31010012 - 6 Mar 2024
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Opioid abuse in the United States has been increasing at an alarming rate over the past 20 years. Sex differences are documented for the rates of opioid-related overdoses, abuse patterns, and drug-induced physiological effects. In our previous study, we demonstrated that chronic oxycodone
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Opioid abuse in the United States has been increasing at an alarming rate over the past 20 years. Sex differences are documented for the rates of opioid-related overdoses, abuse patterns, and drug-induced physiological effects. In our previous study, we demonstrated that chronic oxycodone administration in young female rats is associated with neurodegeneration in the brain. Males and females are susceptible to neurodegenerative diseases via differing mechanisms. To investigate whether opioid exposure affects males and females differently, we treated young mice with chronic morphine. We observed that females had stronger antinociceptive responses to acute morphine and showed a delayed development of tolerance. Males had a higher basal Bax level in the brain that correlated with a higher number of apoptotic cells. Morphine increased Bax levels in both males and females without affecting the numbers of apoptotic cells. Morphine increased activated caspase 3 in axons and increased the MBP level in plasma only in females, suggesting a demyelination process. Our data suggest that males are protected from demyelination by having a higher basal BDNF level. Altogether, our results suggest that males and females have different molecular signaling underlying their patterns in the development of morphine tolerance and drug-induced neuronal degeneration.
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Open AccessConference Report
Emerging Trends in Pathophysiology: Insights from the 9th International Congress of the International Society for Pathophysiology (ISP 2023)
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Anatolii Kubyshkin, Sergey Bolevich, Leonid Churilov, Vladimir Jakovljevic, Evgeniia Kovalenko and Aleksandr Korovin
Pathophysiology 2024, 31(1), 147-151; https://doi.org/10.3390/pathophysiology31010011 - 4 Mar 2024
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This article provides a summary of the 9th International Congress of the International Society for Pathophysiology (ISP 2023) which took place in Belgrade, Serbia, from 4 to 6 July 2023. It describes the main trends and the most promising areas of research in
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This article provides a summary of the 9th International Congress of the International Society for Pathophysiology (ISP 2023) which took place in Belgrade, Serbia, from 4 to 6 July 2023. It describes the main trends and the most promising areas of research in current pathophysiology, including investigations of new pathogenic pathways, and the identification of cellular and molecular mechanisms, target molecules, genetic mechanisms, and new therapeutic strategies. The present article also highlights the research conducted by leading scientific teams and national pathophysiological societies from various countries that adds to our understanding of the pathogenesis of diseases and pathological processes.
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Open AccessArticle
Circadian Rhythms of Body Temperature and Locomotor Activity in Spontaneously Hypertensive Rats under Frequent Changes in Light Conditions
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Anna Yu. Ryabinina, Anna A. Bryk, Mikhail L. Blagonravov, Vyacheslav A. Goryachev, Andrey A. Mozhaev and Vera S. Ovechkina
Pathophysiology 2024, 31(1), 127-146; https://doi.org/10.3390/pathophysiology31010010 - 1 Mar 2024
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Changes in lighting accompany modern urbanization trends and can lead to various pathologies based on circadian disturbances. In this study, we assessed the changes in the circadian rhythm of core body temperature (Tcore) and locomotor activity of Wistar-Kyoto rats (WKY) and spontaneously hypertensive
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Changes in lighting accompany modern urbanization trends and can lead to various pathologies based on circadian disturbances. In this study, we assessed the changes in the circadian rhythm of core body temperature (Tcore) and locomotor activity of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) following exposure to different lighting conditions: extended light phase of the day (16 h–8 h, 20 h–4 h, 24 h–0 h), light pollution, monochromatic light, and bright light therapy. The telemetry data was collected after experimental lighting conditions during periods with standard lighting (12 h of light and 12 h of darkness) and was processed using linear and cosinor analysis. The daily rhythms of rats’ parameters persisted in accordance with the standard lighting regime. Tcore changes were observed in both groups compared to the initial period: in WKY, a decrease in Tcore during the darkness and an increase during the light; in SHR, the opposite trend, with Tcore increased during the darkness and decreased during the light phase of the day. A relationship between Tcore and activity was observed with weak correlation. WKY exhibited more pronounced signs of adaptive variation and desynchronization compared to SHR, which could be associated with a wider range of functional capabilities of the organism without cardiovascular pathology.
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Open AccessBrief Report
Inhibition of miR-33a-5p in Macrophage-like Cells In Vitro Promotes apoAI-Mediated Cholesterol Efflux
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Olanrewaju Oladosu, Emma Chin, Christian Barksdale, Rhonda R. Powell, Terri Bruce and Alexis Stamatikos
Pathophysiology 2024, 31(1), 117-126; https://doi.org/10.3390/pathophysiology31010009 - 28 Feb 2024
Abstract
Atherosclerosis is caused by cholesterol accumulation within arteries. The intima is where atherosclerotic plaque accumulates and where lipid-laden foam cells reside. Intimal foam cells comprise of both monocyte-derived macrophages and macrophage-like cells (MLC) of vascular smooth muscle cell (VSMC) origin. Foam cells can
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Atherosclerosis is caused by cholesterol accumulation within arteries. The intima is where atherosclerotic plaque accumulates and where lipid-laden foam cells reside. Intimal foam cells comprise of both monocyte-derived macrophages and macrophage-like cells (MLC) of vascular smooth muscle cell (VSMC) origin. Foam cells can remove cholesterol via apoAI-mediated cholesterol efflux and this process is regulated by the transporter ABCA1. The microRNA miR-33a-5p is thought to be atherogenic via silencing ABCA1 which promotes cholesterol retention and data has shown inhibiting miR-33a-5p in macrophages may be atheroprotective via enhancing apoAI-mediated cholesterol efflux. However, it is not entirely elucidated whether precisely inhibiting miR-33a-5p in MLC also increases ABCA1-dependent cholesterol efflux. Therefore, the purpose of this work is to test the hypothesis that inhibition of miR-33a-5p in cultured MLC enhances apoAI-mediated cholesterol efflux. In our study, we utilized the VSMC line MOVAS cells in our experiments, and cholesterol-loaded MOVAS cells to convert this cell line into MLC. Inhibition of miR-33a-5p was accomplished by transducing cells with a lentivirus that expresses an antagomiR directed at miR-33a-5p. Expression of miR-33a-5p was analyzed by qRT-PCR, ABCA1 protein expression was assessed via immunoblotting, and apoAI-mediated cholesterol efflux was measured using cholesterol efflux assays. In our results, we demonstrated that lentiviral vector-mediated knockdown of miR-33a-5p resulted in decreasing expression of this microRNA in cultured MLC. Moreover, reduction of miR-33a-5p in cultured MLC resulted in de-repression of ABCA1 expression, which caused ABCA1 protein upregulation in cultured MLC. Additionally, this increase in ABCA1 protein expression resulted in enhancing ABCA1-dependent cholesterol efflux through increasing apoAI-mediated cholesterol efflux in cultured MLC. From these findings, we conclude that inhibiting miR-33a-5p in MLC may protect against atherosclerosis by promoting ABCA1-dependent cholesterol efflux.
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(This article belongs to the Collection Feature Papers in Pathophysiology)
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Open AccessArticle
Rab11a Controls Cell Shape via C9orf72 Protein: Possible Relationships to Frontotemporal Dementia/Amyotrophic Lateral Sclerosis (FTDALS) Type 1
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Shoya Fukatsu, Hinami Sashi, Remina Shirai, Norio Takagi, Hiroaki Oizumi, Masahiro Yamamoto, Katsuya Ohbuchi, Yuki Miyamoto and Junji Yamauchi
Pathophysiology 2024, 31(1), 100-116; https://doi.org/10.3390/pathophysiology31010008 - 9 Feb 2024
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Abnormal nucleotide insertions of C9orf72, which forms a complex with Smith–Magenis syndrome chromosomal region candidate gene 8 (SMCR8) protein and WD repeat-containing protein 41 (WDR41) protein, are associated with an autosomal-dominant neurodegenerative frontotemporal dementia and/or amyotrophic lateral sclerosis type 1 (FTDALS1). The differentially
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Abnormal nucleotide insertions of C9orf72, which forms a complex with Smith–Magenis syndrome chromosomal region candidate gene 8 (SMCR8) protein and WD repeat-containing protein 41 (WDR41) protein, are associated with an autosomal-dominant neurodegenerative frontotemporal dementia and/or amyotrophic lateral sclerosis type 1 (FTDALS1). The differentially expressed in normal and neoplastic cells (DENN) domain-containing C9orf72 and its complex with SMCR8 and WDR41 function as a guanine-nucleotide exchange factor for Rab GTP/GDP-binding proteins (Rab GEF, also called Rab activator). Among Rab proteins serving as major effectors, there exists Rab11a. However, it remains to be established which Rab protein is related to promoting or sustaining neuronal morphogenesis or homeostasis. In this study, we describe that the knockdown of Rab11a decreases the expression levels of neuronal differentiation marker proteins, as well as the elongation of neurite-like processes, using N1E-115 cells, a well-utilized neuronal differentiation model. Similar results were obtained in primary cortical neurons. In contrast, the knockdown of Rab11b, a Rab11a homolog, did not significantly affect their cell morphological changes. It is of note that treatment with hesperetin, a citrus flavonoid (also known as Vitamin P), recovered the neuronal morphological phenotypes induced by Rab11a knockdown. Also, the knockdown of Rab11a or Rab11b led to a decrease in glial marker expression levels and in morphological changes in FBD-102b cells, which serve as the oligodendroglial differentiation model. Rab11a is specifically involved in the regulation of neuronal morphological differentiation. The knockdown effect mimicking the loss of function of C9orf72 is reversed by treatment with hesperetin. These findings may reveal a clue for identifying one of the potential molecular and cellular phenotypes underlying FTDALS1.
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Open AccessArticle
High Glucose Induces Oxidative Stress That Alters Glycocalyx Proteoglycan Levels in Primary Rat Retinal Microvascular Endothelial Cells and in Isolated Ophthalmic Arteries
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Ivan A. Alvarez, Minsup Lee, Randa S. Eshaq, Wendy Leskova and Norman R. Harris
Pathophysiology 2024, 31(1), 89-99; https://doi.org/10.3390/pathophysiology31010007 - 6 Feb 2024
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Our purpose in this study was to identify the role played by oxidative stress in the changes to proteoglycans that occur under hyperglycemic conditions, using primary rat retinal microvascular endothelial cells (RRMEC) and cultured ophthalmic arteries. The cells and blood vessels obtained from
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Our purpose in this study was to identify the role played by oxidative stress in the changes to proteoglycans that occur under hyperglycemic conditions, using primary rat retinal microvascular endothelial cells (RRMEC) and cultured ophthalmic arteries. The cells and blood vessels obtained from rats were cultured in normal glucose (5.6 mM) and high glucose (25 mM) with or without N-acetylcysteine (NAC), an antioxidant. Intracellular oxidative stress was determined by measuring dihydroethidium (DHE) fluorescence and malondialdehyde (MDA)-modified protein levels. mRNA and protein levels were evaluated using quantitative real-time polymerase chain reaction and immunoblot, respectively. High glucose increased levels of glypican-1 mRNA and protein. The level of syndecan-1 mRNA also was increased, but its protein level was decreased, by high glucose. Evaluation of DHE and MDA showed that high glucose increased oxidative stress. These changes caused by high glucose were significantly reversed by NAC treatment. Matrix metalloproteinase-9 (MMP-9) levels, which increased under high glucose conditions, were suppressed by NAC treatment. Oxidative stress caused by hyperglycemia may be responsible for significant changes to the ocular endothelial glycocalyx.
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Open AccessReview
Gut Microbiome Changes in Anorexia Nervosa: A Comprehensive Review
by
Wendi Zhao, Prabhath Kodancha and Soumitra Das
Pathophysiology 2024, 31(1), 68-88; https://doi.org/10.3390/pathophysiology31010006 - 2 Feb 2024
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Anorexia nervosa (AN) remains a challenging condition in psychiatric management and its pathogenesis is not yet fully understood. An imbalance in the gut microbiota composition may contribute to its pathophysiology. This review aims to explore the link between the human gut microbiota and
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Anorexia nervosa (AN) remains a challenging condition in psychiatric management and its pathogenesis is not yet fully understood. An imbalance in the gut microbiota composition may contribute to its pathophysiology. This review aims to explore the link between the human gut microbiota and AN (objective 1) or refeeding syndrome in AN (objective 2). The online databases MEDLINE and PsycINFO were searched for relevant studies. A total of 14 studies met the inclusion and exclusion criteria and only answered objective 1. A total of 476 AN patients, 554 healthy-weight (HC) controls, and 0 patients with other psychiatric disorders were included. Compared to HC, there were consistently reduced abundances of Faecalibacterium prausnitzii and Roseburia inulinivorans, and increased Methanobrevibacter smithii, in AN patients. Changes in alpha diversity were inconsistent, while beta diversity increased in four of six studies. Our model suggests that an imbalance in gut microbiota composition leads to reduced short-chain fatty acids, contributing to a proinflammatory state in AN, which is also common in other psychiatric comorbidities. Microbial changes may also contribute to the semistarvation state through endocrine changes and altered energy utilization.
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Open AccessReview
A Bird’s-Eye View of the Pathophysiologic Role of the Human Urobiota in Health and Disease: Can We Modulate It?
by
Emilio Jirillo, Raffaele Palmirotta, Marica Colella and Luigi Santacroce
Pathophysiology 2024, 31(1), 52-67; https://doi.org/10.3390/pathophysiology31010005 - 1 Feb 2024
Abstract
For a long time, urine has been considered sterile in physiological conditions, thanks to the particular structure of the urinary tract and the production of uromodulin or Tamm–Horsfall protein (THP) by it. More recently, thanks to the development and use of new technologies,
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For a long time, urine has been considered sterile in physiological conditions, thanks to the particular structure of the urinary tract and the production of uromodulin or Tamm–Horsfall protein (THP) by it. More recently, thanks to the development and use of new technologies, i.e., next-generation sequencing and expanded urine culture, the identification of a microbial community in the urine, the so-called urobiota, became possible. Major phyla detected in the urine are represented by Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Particularly, the female urobiota is largely represented by Lactobacillus spp., which are very active against urinary pathogenic Escherichia (E.) coli (UPEC) strains via the generation of lactic acid and hydrogen peroxide. Gut dysbiosis accounts for recurrent urinary tract infections (UTIs), so-called gut–bladder axis syndrome with the formation of intracellular bacterial communities in the course of acute cystitis. However, other chronic urinary tract infections are caused by bacterial strains of intestinal derivation. Monomicrobial and polymicrobial infections account for the outcome of acute and chronic UTIs, even including prostatitis and chronic pelvic pain. E. coli isolates have been shown to be more invasive and resistant to antibiotics. Probiotics, fecal microbial transplantation, phage therapy, antimicrobial peptides, and immune-mediated therapies, even including vaccines for the treatment of UTIs, will be described.
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(This article belongs to the Topic Human Anatomy and Pathophysiology, 2nd Volume)
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Open AccessCase Report
A Refractory Electrical Storm after Acute Myocardial Infarction: The Role of Temporary Ventricular Overdrive Pacing as a Bridge to ICD Implantation
by
Mijo Meter and Josip Andelo Borovac
Pathophysiology 2024, 31(1), 44-51; https://doi.org/10.3390/pathophysiology31010004 - 14 Jan 2024
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An electrical storm (ES) is defined as the presence of at least three episodes of sustained ventricular tachycardia or ventricular fibrillation within 24 h. This patient had a previously known arterial hypertension, type II diabetes mellitus, and chronic kidney disease and has presented
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An electrical storm (ES) is defined as the presence of at least three episodes of sustained ventricular tachycardia or ventricular fibrillation within 24 h. This patient had a previously known arterial hypertension, type II diabetes mellitus, and chronic kidney disease and has presented to the Emergency Department (ED) with symptoms of retrosternal chest pain lasting for several hours prior. The initial 12-lead electrocardiogram revealed ST segment elevation in the anterior leads (V1–V6). Emergent coronary angiography revealed an acute occlusion of the proximal left anterior descending artery (pLAD) and percutaneous coronary intervention was performed with successful implantation of one drug-eluting stent in the pLAD. On day 8 of hospitalization, the patient developed a refractory ES for which he received 50 DC shocks and did not respond to multiple lines of antiarrhythmic medications. Due to a failure of medical therapy, we decided to implant a temporary pacemaker and initiate ventricular overdrive pacing (VOP) that was successful in terminating ES. Following electrical stabilization, the patient underwent a successful ICD implantation. This case demonstrates that VOP can contribute to hemodynamic and electrical stabilization of a patient that suffers from refractory ES and this treatment modality might serve as a temporary bridge to ICD implantation.
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Open AccessReview
Opportunities and Challenges in Catheter-Based Irreversible Electroporation for Ventricular Tachycardia
by
Matthew Leonard Repp and Ikeotunye Royal Chinyere
Pathophysiology 2024, 31(1), 32-43; https://doi.org/10.3390/pathophysiology31010003 - 10 Jan 2024
Cited by 2
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The use of catheter-based irreversible electroporation in clinical cardiac laboratories, termed pulsed-field ablation (PFA), is gaining international momentum among cardiac electrophysiology proceduralists for the non-thermal management of both atrial and ventricular tachyrhythmogenic substrates. One area of potential application for PFA is in the
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The use of catheter-based irreversible electroporation in clinical cardiac laboratories, termed pulsed-field ablation (PFA), is gaining international momentum among cardiac electrophysiology proceduralists for the non-thermal management of both atrial and ventricular tachyrhythmogenic substrates. One area of potential application for PFA is in the mitigation of ventricular tachycardia (VT) risk in the setting of ischemia-mediated myocardial fibrosis, as evidenced by recently published clinical case reports. The efficacy of tissue electroporation has been documented in other branches of science and medicine; however, ventricular PFA’s potential advantages and pitfalls are less understood. This comprehensive review will briefly summarize the pathophysiological mechanisms underlying VT and then summarize the pre-clinical and adult clinical data published to date on PFA’s effectiveness in treating monomorphic VT. These data will be contrasted with the effectiveness ascribed to thermal cardiac ablation modalities to treat VT, namely radiofrequency energy and liquid nitrogen-based cryoablation.
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