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Pathophysiology, Volume 28, Issue 1 (March 2021) – 12 articles

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13 pages, 1119 KiB  
Article
Effects of Aqueous Extract of Lycopersicum esculentum L. var. “Camone” Tomato on Blood Pressure, Behavior and Brain Susceptibility to Oxidative Stress in Spontaneously Hypertensive Rats
by Maria Frosini, Paola Marcolongo, Alessandra Gamberucci, Gabriella Tamasi, Alessio Pardini, Roberta Giunti, Paolo Fiorenzani, Anna Maria Aloisi, Claudio Rossi and Federica Pessina
Pathophysiology 2021, 28(1), 189-201; https://0-doi-org.brum.beds.ac.uk/10.3390/pathophysiology28010012 - 18 Mar 2021
Cited by 3 | Viewed by 2444
Abstract
Behavioral disorders affect millions of people worldwide. Hypertension contributes to both the development and progression of brain damage and cognitive dysfunction and could represent the most powerful modifiable risk factor for cerebral vessel dysfunction and consequent behavioral impairment. Tomato contains antioxidants and bioactive [...] Read more.
Behavioral disorders affect millions of people worldwide. Hypertension contributes to both the development and progression of brain damage and cognitive dysfunction and could represent the most powerful modifiable risk factor for cerebral vessel dysfunction and consequent behavioral impairment. Tomato contains antioxidants and bioactive molecules that might play an important role in the prevention of cardiovascular and brain diseases. The effects of the combined gel and serum from Lycopersicum esculentum L. var. “Camone” tomatoes and those of purified tomato glycoalkaloids (tomatine) and an antihypertensive drug (captopril) were investigated in male spontaneously hypertensive rats (SHRs) and compared with normotensive Wistar Kyoto (WKY) rats. Body weight, systolic blood pressure, behavioral parameters, as well as brain susceptibility to oxidative stress and brain cytokine contents, were assessed. Treating hypertensive rats with tomato gel/serum or captopril for four weeks caused a significant reduction in blood pressure, decreased locomotor activity and increased grooming behavior; the last two parameters were also significantly affected by tomatine treatment. Brain slices obtained from hypertensive rats treated with tomato gel/serum were more resistant to oxidative stress and contained lower levels of inflammatory cytokines than vehicle-treated ones. In contrast, tomatine treatment had no effect. In conclusion, the tomato-derived gel/serum can be considered a dietary supplement able to drive in vivo blood pressure towards healthier values and also control some central effects such as behavior and brain oxidative stress. Full article
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34 pages, 3282 KiB  
Review
Pathophysiology of Lung Disease and Wound Repair in Cystic Fibrosis
by Massimo Conese and Sante Di Gioia
Pathophysiology 2021, 28(1), 155-188; https://0-doi-org.brum.beds.ac.uk/10.3390/pathophysiology28010011 - 10 Mar 2021
Cited by 9 | Viewed by 4504
Abstract
Cystic fibrosis (CF) is an autosomal recessive, life-threatening condition affecting many organs and tissues, the lung disease being the chief cause of morbidity and mortality. Mutations affecting the CF Transmembrane Conductance Regulator (CFTR) gene determine the expression of a dysfunctional protein [...] Read more.
Cystic fibrosis (CF) is an autosomal recessive, life-threatening condition affecting many organs and tissues, the lung disease being the chief cause of morbidity and mortality. Mutations affecting the CF Transmembrane Conductance Regulator (CFTR) gene determine the expression of a dysfunctional protein that, in turn, triggers a pathophysiological cascade, leading to airway epithelium injury and remodeling. In vitro and in vivo studies point to a dysregulated regeneration and wound repair in CF airways, to be traced back to epithelial CFTR lack/dysfunction. Subsequent altered ion/fluid fluxes and/or signaling result in reduced cell migration and proliferation. Furthermore, the epithelial-mesenchymal transition appears to be partially triggered in CF, contributing to wound closure alteration. Finally, we pose our attention to diverse approaches to tackle this defect, discussing the therapeutic role of protease inhibitors, CFTR modulators and mesenchymal stem cells. Although the pathophysiology of wound repair in CF has been disclosed in some mechanisms, further studies are warranted to understand the cellular and molecular events in more details and to better address therapeutic interventions. Full article
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39 pages, 12240 KiB  
Article
Mathematical Modeling of Ion Quantum Tunneling Reveals Novel Properties of Voltage-Gated Channels and Quantum Aspects of Their Pathophysiology in Excitability-Related Disorders
by Abdallah Barjas Qaswal, Omar Ababneh, Lubna Khreesha, Abdallah Al-Ani, Ahmad Suleihat and Mutaz Abbad
Pathophysiology 2021, 28(1), 116-154; https://0-doi-org.brum.beds.ac.uk/10.3390/pathophysiology28010010 - 07 Mar 2021
Cited by 8 | Viewed by 4404
Abstract
Voltage-gated channels are crucial in action potential initiation and propagation and there are many diseases and disorders related to them. Additionally, the classical mechanics are the main mechanics used to describe the function of the voltage-gated channels and their related abnormalities. However, the [...] Read more.
Voltage-gated channels are crucial in action potential initiation and propagation and there are many diseases and disorders related to them. Additionally, the classical mechanics are the main mechanics used to describe the function of the voltage-gated channels and their related abnormalities. However, the quantum mechanics should be considered to unravel new aspects in the voltage-gated channels and resolve the problems and challenges that classical mechanics cannot solve. In the present study, the aim is to mathematically show that quantum mechanics can exhibit a powerful tendency to unveil novel electrical features in voltage-gated channels and be used as a promising tool to solve the problems and challenges in the pathophysiology of excitability-related diseases. The model of quantum tunneling of ions through the intracellular hydrophobic gate is used to evaluate the influence of membrane potential and gating free energy on the tunneling probability, single channel conductance, and quantum membrane conductance. This evaluation is mainly based on graphing the mathematical relationships between these variables. The obtained mathematical graphs showed that ions can achieve significant quantum membrane conductance, which can affect the resting membrane potential and the excitability of cells. In the present work, quantum mechanics reveals original electrical properties associated with voltage-gated channels and introduces new insights and implications into the pathophysiology of excitability- related disorders. In addition, the present work sets a mathematical and theoretical framework that can be utilized to conduct experimental studies in order to explore the quantum aspects of voltage-gated channels and the quantum bioelectrical property of biological membranes. Full article
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18 pages, 2651 KiB  
Article
Moringa oleifera Extract Extenuates Echis ocellatus Venom-Induced Toxicities, Histopathological Impairments and Inflammation via Enhancement of Nrf2 Expression in Rats
by Akindele O. Adeyi, Sodiq O. Adeyemi, Enoh-Obong P. Effiong, Babafemi S. Ajisebiola, Olubisi E. Adeyi and Adewale S. James
Pathophysiology 2021, 28(1), 98-115; https://0-doi-org.brum.beds.ac.uk/10.3390/pathophysiology28010009 - 05 Mar 2021
Cited by 4 | Viewed by 2340
Abstract
Echis ocellatus snakebite causes more fatalities than all other African snake species combined. Moringa oleifera reportedly possesses an antivenom property. Therefore, we evaluated the effectiveness of M. oleifera ethanol extract (MOE) against E. ocellatus venom (EOV) toxicities. Thirty male rats were grouped as [...] Read more.
Echis ocellatus snakebite causes more fatalities than all other African snake species combined. Moringa oleifera reportedly possesses an antivenom property. Therefore, we evaluated the effectiveness of M. oleifera ethanol extract (MOE) against E. ocellatus venom (EOV) toxicities. Thirty male rats were grouped as follows (n = 5): Group 1 (normal control received saline), groups 2 to 6 were administered intraperitoneally, 0.22 mg/kg (LD50) of EOV. Group 2 was left untreated while group 3 to 6 were treated post-envenoming with 0.2 mL of polyvalent antivenom, 200, 400, and 600 mg/kg of MOE respectively. MOE significantly (p < 0.05) normalized the altered haematological indices and blood electrolytes profiles. MOE attenuated venom-induced cellular dysfunctions, characterized by a significant increase in NRF2, and concomitant downregulation of increased antioxidant enzymes (SOD and CAT) activities in the serum and heart of the treated rats. MOE normalized the elevated TNF-α and IL-1β in serum and heart tissues. Furthermore, the IgG titre value was significantly (p < 0.5) higher in the envenomed untreated group compared to the MOE-treated groups. Hemorrhagic, hemolytic and coagulant activities of the venom were strongly inhibited by the MOE dose, dependently. Lesions noticed on tissues of vital organs of untreated rats were abolished by MOE. Our findings substantiate the effectiveness of MOE as a potential remedy against EOV toxicities. Full article
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12 pages, 2150 KiB  
Article
Candesartan Normalizes Changes in Retinal Blood Flow and p22phox in the Diabetic Rat Retina
by Randa S. Eshaq, Megan N. Watts, Patsy R. Carter, Wendy Leskova, Tak Yee Aw, Jonathan Steven Alexander and Norman R. Harris
Pathophysiology 2021, 28(1), 86-97; https://0-doi-org.brum.beds.ac.uk/10.3390/pathophysiology28010008 - 02 Mar 2021
Cited by 2 | Viewed by 2280
Abstract
Angiotensin II has been implicated in the progression of diabetic retinopathy, which is characterized by altered microvasculature, oxidative stress, and neuronal dysfunction. The signaling induced by angiotensin II can occur not only via receptor-mediated calcium release that causes vascular constriction, but also through [...] Read more.
Angiotensin II has been implicated in the progression of diabetic retinopathy, which is characterized by altered microvasculature, oxidative stress, and neuronal dysfunction. The signaling induced by angiotensin II can occur not only via receptor-mediated calcium release that causes vascular constriction, but also through a pathway whereby angiotensin II activates NADPH oxidase to elicit the formation of reactive oxygen species (ROS). In the current study, we administered the angiotensin II receptor antagonist candesartan (or vehicle, in untreated animals) in a rat model of type 1 diabetes in which hyperglycemia was induced by injection of streptozotocin (STZ). Eight weeks after the STZ injection, untreated diabetic rats were found to have a significant increase in tissue levels of angiotensin converting enzyme (ACE; p < 0.05) compared to non-diabetic controls, a 33% decrease in retinal blood flow rate (p < 0.001), and a dramatic increase in p22phox (a subunit of the NADPH oxidase). The decrease in retinal blood flow, and the increases in retinal ACE and p22phox in the diabetic rats, were all significantly attenuated (p < 0.05) by the administration of candesartan in drinking water within one week. Neither STZ nor candesartan induced any changes in tissue levels of superoxide dismutase (SOD-1), 4-hydroxynonenal (4-HNE), or nitrotyrosine. We conclude that one additional benefit of candesartan (and other angiotensin II antagonists) may be to normalize retinal blood flow, which may have clinical benefits in diabetic retinopathy. Full article
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10 pages, 920 KiB  
Article
Risk Stratification in Post-ERCP Pancreatitis: How Do Procedures, Patient Characteristics and Clinical Indicators Influence Outcomes?
by Kapil Kohli, Hrishikesh Samant, Kashif Khan, Sudha Pandit, Kelli Morgan, Urska Cvek, Phillip Kilgore, Marjan Trutschl, Eleni Mijalis, Paul Jordan, James Morris, Moheb Boktor and Jonathan Steven Alexander
Pathophysiology 2021, 28(1), 76-85; https://0-doi-org.brum.beds.ac.uk/10.3390/pathophysiology28010007 - 20 Feb 2021
Cited by 2 | Viewed by 2236
Abstract
Background. Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remains common, and severe complications are associated with ERCP. There is no previous study detailing the effect of race and gender in a US-based population on risk of PEP. Methods. Data were collected on 269 “first-performed” [...] Read more.
Background. Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remains common, and severe complications are associated with ERCP. There is no previous study detailing the effect of race and gender in a US-based population on risk of PEP. Methods. Data were collected on 269 “first-performed” consecutive ERCPs followed by division by race (White vs. African-American) and sex (Female vs. Male). A total of 53 probable risk factors were evaluated by uni- and multivariate analysis followed by outcomes expressed as an odds ratio (OR) (with a 95% confidence interval, 95% CI). Finally, a principal component analysis was performed to construct a risk prediction model for PEP, which can be used by clinicians at bedside. Results. After analyzing the risk factors based on race and gender-based groups, Caucasian males with PEP are more likely to have prior history of pancreatitis (p = 0.009), lower hemoglobin (p = 0.02)/blood urea nitrogen (BUN) (p = 0.01)/creatinine before ERCP (p = 0.07) and lower BUN (p = 0.01)/creatinine after ERCP (p = 0.07), while Caucasian females with PEP are more likely to have higher white blood cell (WBC) count before ERCP (p = 0.08) and lower amylase (p = 0.10)/bilirubin (p = 0.09)/aspartate aminotransferase (AST) after ERCP (p = 0.08). African-American males with PEP are more likely to have lower weight (p = 0.001)/smaller height (p = 0.0005)/lower alkaline phosphatase (p = 0.002)/AST (p = 0.04)/alanine transaminase (ALT) (p = 0.03) before ERCP and lower alkaline phosphatase (p = 0.002)/AST (p = 0.01)/ALT (p = 0.004) after ERCP, while African-American females with PEP are more likely to have prior history of pancreatitis (p = 0.004)/higher lipase before (p = 0.0001) and after (p = 0.05) ERCP along with increased risk with pancreatic duct cannulation (p = 0.0001) and injection (p = 0.0001)/biliary sphincterotomy (p = 0.0001). Importantly, prior history of ERCP, elevated AST after ERCP, and BUN prior to ERCP were found to be important clinical features predicting post-ERCP pancreatitis. To our knowledge, this is a first known attempt at developing a risk scoring system for PEP in a US population with decision tree learning. Conclusions. It is very evident that both patient and procedure-related risk factors vary by race and gender in the US population, leading to the development of a new risk assessment tool for PEP that can be used in clinical practice. We need to follow up with a larger prospective study to validate this novel race and gender-based risk scoring system for PEP. Full article
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12 pages, 2025 KiB  
Article
Amyloid Beta Peptides and Th1 Cytokines Modulate Human Brain Vascular Smooth Muscle Tonic Contractile Capacity In Vitro: Relevance to Alzheimer’s Disease?
by J. Winny Yun, Caretia Washington, Joi McCormick, Emily Stevenson and J. Steven Alexander
Pathophysiology 2021, 28(1), 64-75; https://0-doi-org.brum.beds.ac.uk/10.3390/pathophysiology28010006 - 11 Feb 2021
Cited by 2 | Viewed by 2019
Abstract
Alzheimer’s Disease (AD) is a neurodegenerative condition characterized both by the presence of tau protein neurofibrillary tangles and amyloid beta (Aβ) containing extracellular “plaques”. The cleavage of amyloid precursor protein (APP) yields several Aβ peptides. Although Aβ toxicity to neurons has been described [...] Read more.
Alzheimer’s Disease (AD) is a neurodegenerative condition characterized both by the presence of tau protein neurofibrillary tangles and amyloid beta (Aβ) containing extracellular “plaques”. The cleavage of amyloid precursor protein (APP) yields several Aβ peptides. Although Aβ toxicity to neurons has been described extensively, its effects on other components of the neurovasculature such as vascular smooth muscle cells have been less well characterized. AD is now also recognized as a neurovascular disease characterized by cerebral microbleeds and disturbances in autoregulation. AD is also a neuroinflammatory condition in which several proinflammatory cytokines are elevated and may contribute to the intensification of AD severity. Cerebral autoregulation (the mechanism by which brain blood flow is maintained despite changes in perfusion pressure) is extremely tightly controlled in the brain and shows disturbances in AD. The failure of autoregulation in AD may make the brain susceptible to cerebral microbleeds through a reduced capacity to limit blood flow when pressure is increased. Conversely, reduced vasodilation during low flow might could also exacerbate tissue hypoxia. Currently, whether and how Aβ peptides and inflammatory cytokines depress brain smooth muscle cell tonic contraction is not known, but could reveal important targets in the preservation of autoregulation which is disturbed in AD. We used a collagen gel contractility assay to evaluate the influence of Aβ25-35, Aβ1-40 and Aβ1-42 peptides and inflammatory cytokines on the tonic contractility of human brain vascular smooth muscle cells (HBVSMC) as an in vitro model of cerebral autoregulation. We found that 5 and 10 μM Aβ1-42 significantly depressed HBVSM contractility, while Aβ1-40 5–20 μM had no effect on contractility. Conversely, Aβ25-35 (1–50 μM) increased contractility. Interestingly, the inflammatory cytokines TNF-α (20 ng/mL), IL-1β (20 ng/mL) and IFN-γ (1000 U/mL) also depressed HBVSM tonic contractility alone and in combination. These data suggest that both the inflammatory milieu in AD as well as the abundance of Aβ peptides may promote autoregulatory failure and increase brain susceptibility to dysregulated perfusion and microbleeds which are an important and devastating characteristic of AD. Full article
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14 pages, 4334 KiB  
Article
Coenzyme Q10 and Silymarin Reduce CCl4-Induced Oxidative Stress and Liver and Kidney Injury in Ovariectomized Rats—Implications for Protective Therapy in Chronic Liver and Kidney Diseases
by Samanta Sifat Lamia, Tushar Emran, Jubaida Khatun Rikta, Nowreen Islam Chowdhury, Manoneeta Sarker, Preeti Jain, Tabinda Islam, Zarin Tasnim Gias, Manik Chandra Shill and Hasan Mahmud Reza
Pathophysiology 2021, 28(1), 50-63; https://0-doi-org.brum.beds.ac.uk/10.3390/pathophysiology28010005 - 18 Jan 2021
Cited by 19 | Viewed by 4160
Abstract
Oxidative stress is one of the key factors in the pathophysiology of liver disease. The present study aimed to evaluate the potential impact of two antioxidants, namely coenzyme Q10 (CoQ10) and silymarin, on carbon tetrachloride (CCl4)-induced oxidative stress and hepatic damage [...] Read more.
Oxidative stress is one of the key factors in the pathophysiology of liver disease. The present study aimed to evaluate the potential impact of two antioxidants, namely coenzyme Q10 (CoQ10) and silymarin, on carbon tetrachloride (CCl4)-induced oxidative stress and hepatic damage in ovariectomized rats. Female Long Evans rats were divided into six groups (n = 6): control, CCl4, CCl4 + CoQ10 (200 mg/kg), CCl4 + silymarin (140 mg/kg), Control + CoQ10, and Control + silymarin. Plasma and tissues from liver and kidney were analyzed for oxidative stress parameters and antioxidant enzyme activities using biochemical assays. Infiltration of inflammatory cells and fibrosis were assessed by histological staining of tissue sections. Both CoQ10 and silymarin significantly lowered serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels that were detected to be higher in CCl4 rats compared to controls. Significant reduction in CCl4-induced elevated levels of oxidative stress markers malondialdehyde (MDA), nitric oxide (NO), and advanced protein oxidation product (APOP) was observed with both antioxidants. However, in control rats, CoQ10 and silymarin did not produce a significant effect. Histological analysis revealed that CCl4 markedly increased the level of inflammatory cells infiltration and fibrosis in liver and kidney tissues, but this was significantly reduced in CCl4 + CoQ10 and CCl4 + silymarin groups. Taken together, our results suggest that CoQ10 and silymarin can protect the liver against oxidative damage through improved antioxidant enzyme activities and reduced lipid peroxidation. Thus, supplementation of the aforementioned antioxidants may be useful as a therapeutic intervention to protect liver health in chronic liver diseases. Full article
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16 pages, 8500 KiB  
Brief Report
Is an Immunosuppressive Microenvironment a Characteristic of Both Intra- and Extraparenchymal Central Nervous Tumors?
by Amina Soltani, Bela Kajtar, El Husseiny Mohamed Mahmud Abdelwahab, Anita Steib, Zsolt Horvath, Laszlo Mangel, Luca Jaromi and Judit E. Pongracz
Pathophysiology 2021, 28(1), 34-49; https://0-doi-org.brum.beds.ac.uk/10.3390/pathophysiology28010004 - 08 Jan 2021
Cited by 2 | Viewed by 2345
Abstract
In spite of intensive research, the survival rates of patients diagnosed with tumors of the central nervous system (CNS) have not improved significantly in the last decade. Immunotherapy as novel and efficacious treatment option in several other malignancies has failed in neuro-oncology likely [...] Read more.
In spite of intensive research, the survival rates of patients diagnosed with tumors of the central nervous system (CNS) have not improved significantly in the last decade. Immunotherapy as novel and efficacious treatment option in several other malignancies has failed in neuro-oncology likely due to the immunosuppressive property of the brain tissues. Glioblastoma (GBM) is the most aggressive malignant CNS neoplasm, while meningioma (MNG) is a mainly low grade or benign brain tumor originating from the non-glial tissues of the CNS. The aim of the current preliminary study is to compare the immune microenvironment of MNG and GBM as potential target in immunotherapy. Interestingly, the immune microenvironment of MNG and GBM have proved to be similar. In both tumors types the immune suppressive elements including regulatory T cells (Treg), tumor-associated macrophages (TAM) were highly elevated. The cytokine environment supporting Treg differentiation and the presence of indoleamine 2,3-dioxygenase 1 (IDO1) have also increased the immunosuppressive microenvironment. The results of the present study show an immune suppressive microenvironment in both brain tumor types. In a follow-up study with a larger patient cohort can provide detailed background information on the immune status of individual patients and aid selection of the best immune checkpoint inhibitor or other immune modulatory therapy. Immune modulatory treatments in combination with IDO1 inhibitors might even become alternative therapy for relapsed, multiple and/or malignant MNG or chemo-resistant GBM. Full article
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14 pages, 863 KiB  
Article
Investigation and Functional Enrichment Analysis of the Human Host Interaction Network with Common Gram-Negative Respiratory Pathogens Predicts Possible Association with Lung Adenocarcinoma
by Lydia-Eirini Giannakou, Athanasios-Stefanos Giannopoulos, Chrissi Hatzoglou, Konstantinos I. Gourgoulianis, Erasmia Rouka and Sotirios G. Zarogiannis
Pathophysiology 2021, 28(1), 20-33; https://0-doi-org.brum.beds.ac.uk/10.3390/pathophysiology28010003 - 02 Jan 2021
Viewed by 1934
Abstract
Haemophilus influenzae (Hi), Moraxella catarrhalis (MorCa) and Pseudomonas aeruginosa (Psa) are three of the most common gram-negative bacteria responsible for human respiratory diseases. In this study, we aimed to identify, using the functional enrichment analysis (FEA), the [...] Read more.
Haemophilus influenzae (Hi), Moraxella catarrhalis (MorCa) and Pseudomonas aeruginosa (Psa) are three of the most common gram-negative bacteria responsible for human respiratory diseases. In this study, we aimed to identify, using the functional enrichment analysis (FEA), the human gene interaction network with the aforementioned bacteria in order to elucidate the full spectrum of induced pathogenicity. The Human Pathogen Interaction Database (HPIDB 3.0) was used to identify the human proteins that interact with the three pathogens. FEA was performed via the ToppFun tool of the ToppGene Suite and the GeneCodis database so as to identify enriched gene ontologies (GO) of biological processes (BP), cellular components (CC) and diseases. In total, 11 human proteins were found to interact with the bacterial pathogens. FEA of BP GOs revealed associations with mitochondrial membrane permeability relative to apoptotic pathways. FEA of CC GOs revealed associations with focal adhesion, cell junctions and exosomes. The most significantly enriched annotations in diseases and pathways were lung adenocarcinoma and cell cycle, respectively. Our results suggest that the Hi, MorCa and Psa pathogens could be related to the pathogenesis and/or progression of lung adenocarcinoma via the targeting of the epithelial cellular junctions and the subsequent deregulation of the cell adhesion and apoptotic pathways. These hypotheses should be experimentally validated. Full article
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10 pages, 1737 KiB  
Article
Evidence of Autonomic Dysfunction in Patients with Relapsing-Remitting Multiple Sclerosis: Heart Rate Variability and Cardiovascular Parameters
by Liudmila Gerasimova-Meigal, Ilya Sirenev and Alexander Meigal
Pathophysiology 2021, 28(1), 10-19; https://0-doi-org.brum.beds.ac.uk/10.3390/pathophysiology28010002 - 02 Jan 2021
Cited by 5 | Viewed by 2491
Abstract
This study was aimed at evaluation of autonomic dysfunction in patients with multiple sclerosis (MS) by means of time- and frequency-domain parameters of heart rate variability (HRV) and conventional cardiovascular tests (deep breathing (DB) and active orthostatic test (AOT)). The study group enrolled [...] Read more.
This study was aimed at evaluation of autonomic dysfunction in patients with multiple sclerosis (MS) by means of time- and frequency-domain parameters of heart rate variability (HRV) and conventional cardiovascular tests (deep breathing (DB) and active orthostatic test (AOT)). The study group enrolled 32 patients with the relapsing-remitting MS (17 m, 15 f, aged 29 ± 4.9 years, disease duration 4.2 ± 2.7 years, EDSS scores less than 3.0 and 26 subjects in good health (HC, 15 m, 11 f, aged 30.1 ± 2.7 years). In the MS group, at rest the variability of heart rate was decreased in comparison to the HC group seen by time- (SDNN, RMSSD, pNN50, CV, p < 0.01) and frequency-domain (TP, HF, LF, p < 0.05) parameters, what was indicative of the general decrease of the autonomic neurogenic control of the heart rate, both sympathetic and parasympathetic. The functional tests (DB and AOT) showed reduced cardiovascular reactivity in the MS group. Additionally, the cardio-respiratory synchronization was impaired in the MS group at rest and DB. The severity of HRV deficit in the MS group correlated with the activity of MS. In conclusion, the comprehensive assessment of time- and frequency-domain HRV parameters studied with functional tests provides better insight to understanding autonomic dysfunction in subjects with relapsing-remitting MS. Full article
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9 pages, 272 KiB  
Article
CLOCK 3111TT Genotype Is Associated with Increased Total Cholesterol and Low-Density Lipoprotein Levels in Menopausal Women with a Body Mass Index of at Least 25 kg/m2
by Natalya Semenova, Irina Madaeva, Sergey Kolesnikov, Lyubov Rychkova, Tatjana Bairova, Marina Darenskaya and Lyubov Kolesnikova
Pathophysiology 2021, 28(1), 1-9; https://0-doi-org.brum.beds.ac.uk/10.3390/pathophysiology28010001 - 30 Dec 2020
Cited by 3 | Viewed by 2130
Abstract
Lipid profile comparative analysis was performed to reveal the interdependence of lipids with Circadian locomoter output cycles protein kaput (CLOCK) 3111T/C gene polymorphism in menopausal women with/without a body mass index (BMI) of ≥25 kg/m2. Methods: A total of [...] Read more.
Lipid profile comparative analysis was performed to reveal the interdependence of lipids with Circadian locomoter output cycles protein kaput (CLOCK) 3111T/C gene polymorphism in menopausal women with/without a body mass index (BMI) of ≥25 kg/m2. Methods: A total of 193 female volunteers aged 45 to 60 years were divided into two groups: Those with BMI < 25 kg/m2 (control) and those with BMI ≥ 25 kg/m2. Each group was then divided into two subgroups: Those with the CLOCK TT-genotype and those with the CLOCK TC-, CC-genotypes. Lipid metabolism parameters were determined by the enzymatic method. Single-nucleotide polymorphisms (SNPs) were detected via polymerase chain reaction–restriction fragment length polymorphism technology. Results: There were no differences in CLOCK 3111T/C genotypes or allele frequency between the control and main groups. In addition, there were no differences in lipid profile parameters between women of the control group and different CLOCK 3111T/C genotypes. The total cholesterol (p = 0.041) and low-density lipoprotein cholesterol (p = 0.036) levels were higher in the subgroup of women with a BMI ≥ 25 kg/m2 and CLOCK TT-genotype as compared to the subgroup with a BMI ≥ 25 kg/m2 and minor allele 3111C. Conclusions: SNP 3111T/C of the CLOCK gene is not associated with BMI however, data suggest that the minor allele of the CLOCK 3111T/C gene polymorphism may have a protective role in atherogenic lipid levels in women with a BMI greater than or equal to 25 kg/m2. Full article
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