9,655 results
Search Results
2. Transfer function analysis of dynamic cerebral autoregulation: A white paper from the International Cerebral Autoregulation Research Network.
- Author
-
Claassen JA, Meel-van den Abeelen AS, Simpson DM, and Panerai RB
- Subjects
- Animals, Blood Pressure physiology, Humans, Cerebrovascular Circulation physiology, Homeostasis physiology, Neurophysiology methods
- Abstract
Cerebral autoregulation is the intrinsic ability of the brain to maintain adequate cerebral perfusion in the presence of blood pressure changes. A large number of methods to assess the quality of cerebral autoregulation have been proposed over the last 30 years. However, no single method has been universally accepted as a gold standard. Therefore, the choice of which method to employ to quantify cerebral autoregulation remains a matter of personal choice. Nevertheless, given the concept that cerebral autoregulation represents the dynamic relationship between blood pressure (stimulus or input) and cerebral blood flow (response or output), transfer function analysis became the most popular approach adopted in studies based on spontaneous fluctuations of blood pressure. Despite its sound theoretical background, the literature shows considerable variation in implementation of transfer function analysis in practice, which has limited comparisons between studies and hindered progress towards clinical application. Therefore, the purpose of the present white paper is to improve standardisation of parameters and settings adopted for application of transfer function analysis in studies of dynamic cerebral autoregulation. The development of these recommendations was initiated by (but not confined to) theCerebral Autoregulation Research Network(CARNet -www.car-net.org)., (© The Author(s) 2016.)
- Published
- 2016
- Full Text
- View/download PDF
3. Skin homeostasis: Mechanism and influencing factors.
- Author
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Jiao Q, Zhi L, You B, Wang G, Wu N, and Jia Y
- Subjects
- Humans, Skin Aging physiology, Skin Aging radiation effects, Skin Diseases etiology, Skin Diseases therapy, Ultraviolet Rays adverse effects, Homeostasis physiology, Skin Physiological Phenomena, Skin radiation effects, Skin metabolism
- Abstract
Background: The skin is the largest organ in the human body, not only resisting the invasion of harmful substances, but also preventing the loss of moisture and nutrients. Maintaining skin homeostasis is a prerequisite for the proper functioning of the body. Any damage to the skin can lead to a decrease in local homeostasis, such as ultraviolet radiation, seasonal changes, and air pollution, which can damage the skin tissue and affect the function of the skin barrier., Objective: This article reviews the maintenance mechanism and influencing factors of skin homeostasis and the symptoms of homeostasis imbalance., Methods: We searched for articles published between 1990 and 2022 in English and Chinese using PubMed, Web of Science, CNKI, and other databases in the subject area of dermatology, using the following search terms in various combinations: "skin homeostasis," "skin barrier," and "unstable skin." Based on our results, we further refined our search criteria to include a series of common skin problems caused by the destruction of skin homeostasis and its treatments. Limitations include the lack of research on dermatological and cosmetic problems triggered by the disruption of skin homeostasis., Results: This study describes the neuroendocrine-immune system, skin barrier structure, and skin metabolic system that maintain skin homeostasis. In addition, we discuss several common symptoms that occur when skin homeostasis is out of balance, such as dryness, redness, acne, sensitivity, and aging, and explain the mechanism of these symptoms., Conclusion: This article provides an update and review for students and practitioners, and provides a theoretical basis for the development of skin care products for the maintenance and repair of skin homeostasis., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)
- Published
- 2024
- Full Text
- View/download PDF
4. Commentary to accompany the paper entitled 'nutritional disturbance in acid-base balance and osteoporosis: a hypothesis that disregards the essential homeostatic role of the kidney', by Jean-Philippe Bonjour.
- Author
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Frassetto LA and Sebastian A
- Subjects
- Humans, Acid-Base Equilibrium, Bone and Bones, Homeostasis, Kidney, Osteoporosis etiology
- Published
- 2013
- Full Text
- View/download PDF
5. An American Physiological Society cross-journal Call for Papers on 'Inter-Organ Communication in Homeostasis and Disease'
- Author
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Nigel W. Bunnett, Gina L. C. Yosten, Mark R. Frey, André Marette, Hilary A. Coller, Thomas R. Kleyman, Bina Joe, Morten B. Thomsen, Jan-Marino Ramirez, Merry L. Lindsey, Heddwen L. Brooks, Rory E. Morty, and Sue C. Bodine
- Subjects
Pulmonary and Respiratory Medicine ,Societies, Scientific ,Physiology ,business.industry ,Cell Biology ,Disease ,Cell Communication ,Editorial ,Physiology (medical) ,Medicine ,Homeostasis ,Humans ,Periodicals as Topic ,business ,Neuroscience - Published
- 2021
6. Triad of TDP43 control in neurodegeneration: autoregulation, localization and aggregation.
- Author
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Tziortzouda P, Van Den Bosch L, and Hirth F
- Subjects
- Amyotrophic Lateral Sclerosis pathology, Humans, Neurodegenerative Diseases pathology, Amyotrophic Lateral Sclerosis metabolism, DNA-Binding Proteins metabolism, Homeostasis physiology, Neurodegenerative Diseases metabolism
- Abstract
Cytoplasmic aggregation of TAR DNA-binding protein 43 (TDP43; also known as TARDBP or TDP-43) is a key pathological feature of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP43 typically resides in the nucleus but can shuttle between the nucleus and the cytoplasm to exert its multiple functions, which include regulation of the splicing, trafficking and stabilization of RNA. Cytoplasmic mislocalization and nuclear loss of TDP43 have both been associated with ALS and FTD, suggesting that calibrated levels and correct localization of TDP43 - achieved through an autoregulatory loop and tightly controlled nucleocytoplasmic transport - safeguard its normal function. Furthermore, TDP43 can undergo phase transitions, including its dispersion into liquid droplets and its accumulation into irreversible cytoplasmic aggregates. Thus, autoregulation, nucleocytoplasmic transport and phase transition are all part of an intrinsic control system regulating the physiological levels and localization of TDP43, and together are essential for the cellular homeostasis that is affected in neurodegenerative disease.
- Published
- 2021
- Full Text
- View/download PDF
7. Transfer function analysis of dynamic cerebral autoregulation: A white paper from the International Cerebral Autoregulation Research Network
- Author
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Claassen, J. A., Meel-Van Den Abeelen, A. S. S., Simpson, D. M., Panerai, R. B., Alexander Caicedo Dorado, Mitsis, Georgios D., Brassard, P., Ainslie, Philip N., Summers, P., Iwasaki, K., Ragauskas, A., Tzeng, Y. -C, Müller, M., Wang, C. Y., Hu, H. H., Gommer, E., Karemaker, J. M., Aries, M., Van Lieshout, J. J., Semenyuti, V., Aliev, V., Potter, J., Smielewski, P., Liu, X., Czosnyka, M., Payne, S., Bailey, D., Yelicich, B., Puppo, C., Shin, D., Rickards, C. A., Serrador, J., Zhang, R., Marmarelis, V. Z., Novak, V., MUMC+: HZC Niet Med Staf Klinische Neurofys (9), RS: FHML non-thematic output, RS: MHeNs School for Mental Health and Neuroscience, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, and Mitsis, Georgios D. [0000-0001-9975-5128]
- Subjects
Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1] ,Subarachnoid hemorrhage ,SPONTANEOUS BLOOD-PRESSURE ,CEREBROVASCULAR AUTOREGULATION ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,cerebral blood flow ,Neurophysiology ,Blood Pressure ,030204 cardiovascular system & hematology ,Cerebral autoregulation ,transfer function analysis ,03 medical and health sciences ,white paper ,0302 clinical medicine ,TRANSCRANIAL DOPPLER ,medicine ,OSCILLATIONS ,Animals ,Homeostasis ,Humans ,Autoregulation ,Cerebral perfusion pressure ,Review Articles ,SUBARACHNOID HEMORRHAGE ,Transfer function analysis ,FLOW VELOCITY ,gold standard ,QUANTIFICATION ,medicine.disease ,REACTIVITY ,Transcranial Doppler ,FOURIER-TRANSFORM ,Blood pressure ,Neurology ,Cerebral blood flow ,Cerebrovascular Circulation ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,Psychology ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Item does not contain fulltext Cerebral autoregulation is the intrinsic ability of the brain to maintain adequate cerebral perfusion in the presence of blood pressure changes. A large number of methods to assess the quality of cerebral autoregulation have been proposed over the last 30 years. However, no single method has been universally accepted as a gold standard. Therefore, the choice of which method to employ to quantify cerebral autoregulation remains a matter of personal choice. Nevertheless, given the concept that cerebral autoregulation represents the dynamic relationship between blood pressure (stimulus or input) and cerebral blood flow (response or output), transfer function analysis became the most popular approach adopted in studies based on spontaneous fluctuations of blood pressure. Despite its sound theoretical background, the literature shows considerable variation in implementation of transfer function analysis in practice, which has limited comparisons between studies and hindered progress towards clinical application. Therefore, the purpose of the present white paper is to improve standardisation of parameters and settings adopted for application of transfer function analysis in studies of dynamic cerebral autoregulation. The development of these recommendations was initiated by (but not confined to) theCerebral Autoregulation Research Network(CARNet -www.car-net.org).
- Published
- 2015
8. Consensus Paper: Probing Homeostatic Plasticity of Human Cortex With Non-invasive Transcranial Brain Stimulation
- Author
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Joseph Classen, Masashi Hamada, Marcello Massimini, Ulf Ziemann, Hartwig R. Siebner, John C. Rothwell, Anke Ninija Karabanov, Angelo Quartarone, and Mark S. George
- Subjects
Consensus ,medicine.medical_treatment ,Neuroscience(all) ,Biophysics ,Clinical Neurology ,Biology ,Transcranial Direct Current Stimulation ,lcsh:RC321-571 ,Homeostatic plasticity ,Metaplasticity ,Neuroplasticity ,Long-term inhibition ,medicine ,Homeostasis ,Humans ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Cerebral Cortex ,Neuronal Plasticity ,Synaptic scaling ,Neuroscience (all) ,Transcranial direct-current stimulation ,Non-invasive transcranial brain stimulation ,General Neuroscience ,Medicine (all) ,Motor Cortex ,Brain ,Human brain ,Transcranial Magnetic Stimulation ,Transcranial magnetic stimulation ,medicine.anatomical_structure ,Brain stimulation ,Long-term potentiation ,Neurology (clinical) ,Nerve Net ,Synaptic homeostasis hypothesis ,Neuroscience ,Neurology (clinical), Neuroscience (all), Biophysics, Medicine (all) - Abstract
Homeostatic plasticity is thought to stabilize neural activity around a set point within a physiologically reasonable dynamic range. Over the last ten years, a wide range of non-invasive transcranial brain stimulation (NTBS) techniques have been used to probe homeostatic control of cortical plasticity in the intact human brain. Here, we review different NTBS approaches to study homeostatic plasticity on a systems level and relate the findings to both, physiological evidence from in vitro studies and to a theoretical framework of homeostatic function. We highlight differences between homeostatic and other non-homeostatic forms of plasticity and we examine the contribution of sleep in restoring synaptic homeostasis. Finally, we discuss the growing number of studies showing that abnormal homeostatic plasticity may be associated to a range of neuropsychiatric diseases.
- Published
- 2015
- Full Text
- View/download PDF
9. UGT72, a Major Glycosyltransferase Family for Flavonoid and Monolignol Homeostasis in Plants.
- Author
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Speeckaert, Nathanaël, El Jaziri, Mondher, Baucher, Marie, and Behr, Marc
- Subjects
SMALL molecules ,PHENYLPROPANOIDS ,HOMEOSTASIS ,FLAVONOIDS ,PAPER pulp ,PLANT defenses ,LIGNINS - Abstract
Simple Summary: Phenylpropanoids are specialized metabolites playing crucial roles in plant developmental processes and in plant defense towards pathogens. The attachment of sugar moieties to these small hydrophobic molecules renders them more hydrophilic and increases their solubility. The UDP-glycosyltransferase 72 family (UGT72) of plants has been shown to glycosylate mainly two classes of phenylpropanoids, (i) the monolignols that are the building blocks of lignin, the second most abundant polymer after cellulose, and (ii) the flavonoids, which play determinant roles in plant interactions with other organisms and in response to stress. The purpose of this review is to bring an overview of the current knowledge of the UGT72 family and to highlight its role in the homeostasis of these molecules. Potential applications in pharmacology and in wood, paper pulp, and bioethanol production are given within the perspectives. Plants have developed the capacity to produce a diversified range of specialized metabolites. The glycosylation of those metabolites potentially decreases their toxicity while increasing their stability and their solubility, modifying their transport and their storage. The UGT, forming the largest glycosyltransferase superfamily in plants, combine enzymes that glycosylate mainly hormones and phenylpropanoids by using UDP-sugar as a sugar donor. Particularly, members of the UGT72 family have been shown to glycosylate the monolignols and the flavonoids, thereby being involved in their homeostasis. First, we explore primitive UGTs in algae and liverworts that are related to the angiosperm UGT72 family and their role in flavonoid homeostasis. Second, we describe the role of several UGT72s glycosylating monolignols, some of which have been associated with lignification. In addition, the role of other UGT72 members that glycosylate flavonoids and are involved in the development and/or stress response is depicted. Finally, the importance to explore the subcellular localization of UGTs to study their roles in planta is discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
10. Analysis of the Impact of Heat Stress on Embryo Development of Broiler: A Literature Review.
- Author
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Mafruchati, Maslichah, Othman, Nor Hayati, and Wardhana, Akhmad Kusuma
- Subjects
LITERATURE reviews ,CHICKEN embryos ,EMBRYOS ,EMBRYOLOGY ,HIGH temperatures ,HOMEOSTASIS ,HEART beat - Abstract
Temperature is an important factor in embryonic development because temperature plays a role in determining the overall development of the embryo. The effect of high temperature on the embryo will cause the embryo to make a defense by diverting some of its energy to form thermal homeostasis, which is a physiological response. The purpose of this study was to analyze heat stress on embryonic development. This study used a systematic literature review (SLR) following PRISMA guidelines and gathered the sample of papers through the PubMed databases using keywords categorized as heat, stress, and embryo. There were 31 papers used as samples. The result showed that hyperthermia in chickens caused an increase in heart rate per minute as a result of temperature pressure. It affects the hatching percentage, hatching time, weight, and mortality rate in chicken embryos. In summary, heat stress has an impact on embryonic development heat stress gives an impact on the development of embryos. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
11. Teaching the interrelationship between stress, emotions, and cardiovascular risk using a classic paper by Walter Cannon
- Author
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Patricia A. Gwirtz
- Subjects
Models, Educational ,Epinephrine ,Physiology ,media_common.quotation_subject ,Emotions ,Applied psychology ,Cardiovascular control ,medicine.disease_cause ,Risk Assessment ,Education ,Heart disorder ,Risk Factors ,Adrenal Glands ,Pedagogy ,Stress (linguistics) ,medicine ,Homeostasis ,Humans ,Psychological stress ,Function (engineering) ,Curriculum ,media_common ,Teaching ,General Medicine ,Graduate students ,Cardiovascular Diseases ,Active learning ,Psychology ,Stress, Psychological - Abstract
Classroom discussion of the classic article by Walter B. Cannon in 1914, entitled “The emergency function of the adrenal medulla in pain and the major emotions,” is an excellent tool to teach graduate students the interaction between stress, emotions, and cardiovascular function. Using this article, we are able to review important early research by Dr. Cannon, including discussion of his scientific methods and results and how they hold true today. This article outlines how this classic paper is used to allow students to explore basics principles of cardiovascular control during stress. The teaching points that are presented illustrate how students can be directed to understand the interrelationship between chronic stress and cardiovascular disease.
- Published
- 2008
12. Targets and regulation of microRNA-652-3p in homoeostasis and disease.
- Author
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Stevens MT and Saunders BM
- Subjects
- Animals, Biomarkers, Humans, Organ Specificity, Prognosis, Signal Transduction, Disease Susceptibility, Gene Expression Regulation, Neoplastic, Homeostasis, MicroRNAs genetics, RNA Interference, RNA, Messenger genetics
- Abstract
microRNA are small non-coding RNA molecules which inhibit gene expression by binding mRNA, preventing its translation. As important regulators of gene expression, there is increasing interest in microRNAs as potential diagnostic biomarkers and therapeutic targets. Studies investigating the role of one of the miRNA-miR-652-3p-detail diverse roles for this miRNA in normal cell homoeostasis and disease states, including cancers, cardiovascular disease, mental health, and central nervous system diseases. Here, we review recent literature surrounding miR-652-3p, discussing its known target genes and their relevance to disease progression. These studies demonstrate that miR-652-3p targets LLGL1 and ZEB1 to modulate cell polarity mechanisms, with impacts on cancer metastasis and asymmetric cell division. Inhibition of the NOTCH ligand JAG1 by miR-652-3p can have diverse effects on angiogenesis and immune cell regulation. Investigation of miR-652-3p and other dysregulated miRNAs identified a number of pathways potentially regulated by miR-652-3p. This review demonstrates that miR-652-3p has great promise as a diagnostic or therapeutic target due to its activity across multiple cellular systems.
- Published
- 2021
- Full Text
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13. Commentary to accompany the paper entitled ‘Nutritional disturbance in acid–base balance and osteoporosis: a hypothesis that disregards the essential homeostatic role of the kidney’, by Jean-Philippe Bonjour
- Author
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Anthony Sebastian and Lynda A. Frassetto
- Subjects
Gerontology ,Kidney ,Nutrition and Dietetics ,Disturbance (geology) ,business.industry ,Osteoporosis ,MEDLINE ,Medicine (miscellaneous) ,Bioinformatics ,medicine.disease ,medicine.anatomical_structure ,Medicine ,business ,Homeostasis - Published
- 2013
14. Assessment of cerebral autoregulation indices - a modelling perspective.
- Author
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Liu X, Czosnyka M, Donnelly J, Cardim D, Cabeleira M, Lalou DA, Hu X, Hutchinson PJ, and Smielewski P
- Subjects
- Adult, Brain Injuries, Traumatic, Cerebrovascular Circulation physiology, Female, Humans, Male, Cerebrum physiology, Homeostasis physiology, Models, Neurological
- Abstract
Various methodologies to assess cerebral autoregulation (CA) have been developed, including model - based methods (e.g. autoregulation index, ARI), correlation coefficient - based methods (e.g. mean flow index, Mx), and frequency domain - based methods (e.g. transfer function analysis, TF). Our understanding of relationships among CA indices remains limited, partly due to disagreement of different studies by using real physiological signals, which introduce confounding factors. The influence of exogenous noise on CA parameters needs further investigation. Using a set of artificial cerebral blood flow velocities (CBFV) generated from a well-known CA model, this study aims to cross-validate the relationship among CA indices in a more controlled environment. Real arterial blood pressure (ABP) measurements from 34 traumatic brain injury patients were applied to create artificial CBFVs. Each ABP recording was used to create 10 CBFVs corresponding to 10 CA levels (ARI from 0 to 9). Mx, TF phase, gain and coherence in low frequency (LF) and very low frequency (VLF) were calculated. The influence of exogenous noise was investigated by adding three levels of colored noise to the artificial CBFVs. The result showed a significant negative relationship between Mx and ARI (r = -0.95, p < 0.001), and it became almost purely linear when ARI is between 3 to 6. For transfer function parameters, ARI positively related with phase (r = 0.99 at VLF and 0.93 at LF, p < 0.001) and negatively related with gain_VLF(r = -0.98, p < 0.001). Exogenous noise changed the actual values of the CA parameters and increased the standard deviation. Our results show that different methods can lead to poor correlation between some of the autoregulation parameters even under well controlled situations, undisturbed by unknown confounding factors. They also highlighted the importance of exogenous noise, showing that even the same CA value might correspond to different CA levels under different 'noise' conditions.
- Published
- 2020
- Full Text
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15. The upper frequency limit of dynamic cerebral autoregulation.
- Author
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Panerai RB, Robinson TG, and Minhas JS
- Subjects
- Adult, Carbon Dioxide blood, Female, Humans, Male, Middle Aged, Respiration, Biological Variation, Population, Blood Pressure, Cerebrovascular Circulation, Homeostasis
- Abstract
Key Points: Dynamic cerebral autoregulation (CA) is expressed by the temporal pattern of cerebral blood flow (CBF) recovery following a sudden change in arterial blood pressure (BP). Transfer function analysis of BP as input and CBF velocity as output can express dynamic CA through its amplitude (or gain) and phase frequency responses. The upper frequency limit (F
upLim ) at which dynamic CA can operate is of considerable physiological interest and can also provide additional information about worsening CA due to disease processes. In healthy subjects FupLim was strongly dependent on arterial P C O 2 changes induced by four different breathing manoeuvres. The considerable intersubject variability in FupLim suggests that fixed frequency bands should not be adopted for averaging values of gain and phase in studies of dynamic CA., Abstract: Dynamic cerebral autoregulation (CA) can be expressed in the frequency domain by the amplitude and phase frequency responses calculated by transfer function analysis of arterial blood pressure (BP) and cerebral blood flow velocity (CBFV). We studied the effects of arterial P C O 2 ( P aC O 2 ) on the upper frequency limit (FupLim ) of these responses and its intersubject variability. Twenty-four healthy subjects (11 female, age 36.0 ± 13.4 years) were recruited. Recordings of CBFV (transcranial Doppler ultrasound), BP (Finometer) and end-tidal CO2 ( P ETC O 2 , capnography) were performed during 5 min at rest (normocapnia) and during four breathing manoeuvres: 5% and 8% CO2 in air and hyperventilation targeting reductions of 5 and 10 mmHg compared to normocapnia. FupLim was determined by the break point of the autoregulation index (ARI) curve as a function of frequency when the phase response was gradually set to zero. The five breathing conditions led to highly significant differences in P ETC O 2 (p < 0.0001), CBFV (P < 0.0001), ARI (p < 0.0001) and FupLim (p < 0.0001). FupLim ranged from 0.167 ± 0.036 Hz at the lowest values of hypocapnia (28.1 ± 1.9 mmHg) to 0.094 ± 0.040 Hz at the highest level of hypercapnia (41.7 ± 5.4 mmHg), showing a correlation of r = -0.53 (p < 0.001) with P ETC O 2 . These findings reinforce the key role of P aC O 2 in CBF regulation. The considerable intersubject variability of FupLim suggests that fixed frequency bands should not be adopted for averaging values of gain and phase in dynamic CA studies, and that the higher frequency band (0.20-0.40 Hz), in particular, does not contain relevant information about dynamic CA. Further investigations are needed to assess the information value of FupLim as a marker of dynamic CA efficiency in physiological and clinical studies., (© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.)- Published
- 2019
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16. Implications of habitual endurance and resistance exercise for dynamic cerebral autoregulation.
- Author
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Perry BG, Cotter JD, Korad S, Lark S, Labrecque L, Brassard P, Paquette M, Le Blanc O, and Lucas SJE
- Subjects
- Adult, Brain blood supply, Brain diagnostic imaging, Cohort Studies, Female, Humans, Male, Resistance Training trends, Ultrasonography, Doppler methods, Ultrasonography, Doppler trends, Brain physiology, Cerebrovascular Circulation physiology, Habits, Homeostasis physiology, Physical Endurance physiology, Resistance Training methods
- Abstract
New Findings: What is the central question of this study? Does habitual resistance and endurance exercise modify dynamic cerebral autoregulation? What is the main finding and its importance? To the authors' knowledge, this is the first study to directly assess dynamic cerebral autoregulation in resistance-trained individuals, and potential differences between exercise training modalities. Forced oscillations in blood pressure were induced by repeated squat-stands, from which dynamic cerebral autoregulation was assessed using transfer function analysis. These data indicate that dynamic cerebral autoregulatory function is largely unaffected by habitual exercise type, and further document the systemic circulatory effects of regular exercise., Abstract: Regular endurance and resistance exercise produce differential but desirable physiological adaptations in both healthy and clinical populations. The chronic effect of these different exercise modalities on cerebral vessels' ability to respond to rapid changes in blood pressure (BP) had not been examined. We examined dynamic cerebral autoregulation (dCA) in 12 resistance-trained (mean ± SD, 25 ± 6 years), 12 endurance-trained (28 ± 9 years) and 12 sedentary (26 ± 6 years) volunteers. The dCA was assessed using transfer function analysis of forced oscillations in BP vs. middle cerebral artery blood velocity (MCAv), induced via repeated squat-stands at 0.05 and 0.10 Hz. Resting BP and MCAv were similar between groups (interaction: both P ≥ 0.544). The partial pressure of end-tidal carbon dioxide ( P ETC O 2 ) was unchanged (P = 0.561) across squat-stand manoeuvres (grouped mean for absolute change +0.6 ± 2.3 mmHg). Gain and normalized gain were similar between groups across all frequencies (both P ≥ 0.261). Phase showed a frequency-specific effect between groups (P = 0.043), tending to be lower in resistance-trained (0.63 ± 0.21 radians) than in endurance-trained (0.90 ± 0.41, P = 0.052) and -untrained (0.85 ± 0.38, P = 0.081) groups at slower frequency (0.05 Hz) oscillations. Squat-stands induced mean arterial pressure perturbations differed between groups (interaction: P = 0.031), with greater changes in the resistance (P < 0.001) and endurance (P = 0.001) groups compared with the sedentary group at 0.05 Hz (56 ± 13 and 49 ± 11 vs. 35 ± 11 mmHg, respectively). The differences persisted at 0.1 Hz between resistance and sedentary groups (49 ± 12 vs. 33 ± 7 mmHg, P < 0.001). These results indicate that dCA remains largely unaltered by habitual endurance and resistance exercise with a trend for phase to be lower in the resistance exercise group at lower fequencies., (© 2019 The Authors. Experimental Physiology © 2019 The Physiological Society.)
- Published
- 2019
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17. Cellular Reprogramming Call for Papers: Special Issue on Direct Cell Reprogramming.
- Subjects
- *
OPEN access publishing , *EPIGENETICS , *ACQUISITION of manuscripts , *HOMEOSTASIS , *SOMATIC cells - Published
- 2021
- Full Text
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18. Cellular Reprogramming Call for Papers: Special Issue on Direct Cell Reprogramming.
- Subjects
- *
OPEN access publishing , *EPIGENETICS , *HOMEOSTASIS - Published
- 2021
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19. Title of presented paper: The relationship between sleep disturbances and mental health -- literature review and survey research.
- Author
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Czerkiewicz, Karolina, Dyndał, Kinga, and Cybula, Paweł
- Subjects
SLEEP disorders ,MENTAL health ,HOMEOSTASIS ,PSYCHONEUROIMMUNOLOGY ,IMMUNITY - Abstract
Introduction and aim. Sleep is a complex physiological process important for body homeostasis. Sleep and sleep deprivation have been shown to have a significant impact on mental health and psychoneuroimmunology. Sleep deprivation also can lead to an increased susceptibility to infections and other illnesses. Moreover, sleep is crucial for the maintenance of emotional, cognitive, and behavioral functions. Material and methods. A systematic search of the literature (clinical trials and reviews) published in the last five years was performed using PubMed/MEDLINE and Embase. Survey research (n= 555: 404 women and 151 men in the age range 15-30, 23 questions in total) was also conducted by the authors of this study. Analysis of literature. Literature data indicate a decline in immune function caused by sleep deprivation. In addition, a number of mental health problems such as depression and anxiety were caused by sleep disorders. What's more, there is a strong link between the glymphatic system and brain detoxification during sleep. As many as 47% of our respondents noticed a decrease in immunity during periods of sleep deprivation. Immunity is one of the 4 most frequently mentioned factors by respondents that can be affected by lack of sleep. Conclusion. Sleep and sleep deprivation affect mental health and immune responses. Adequate sleep is essential for maintaining optimal health, and addressing sleep problems may help prevent or manage mental health disorders and immune- related diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2023
20. Cellular Reprogramming Call for Papers: Special Issue on Direct Cell Reprogramming.
- Subjects
- *
OPEN access publishing , *EPIGENETICS , *HOMEOSTASIS - Published
- 2021
- Full Text
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21. Wenyang-Tianjing-Jieyu Decoction Improves Depression Rats of Kidney Yang Deficiency Pattern by Regulating T Cell Homeostasis and Inflammation Level.
- Author
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Zhang, Tian, Wang, Jiexin, Wang, Yi, He, Linxi, Lv, Shangbin, Wang, Yiran, and Li, Weihong
- Subjects
- *
T cells , *HOMEOSTASIS , *RATS , *JAK-STAT pathway , *MENTAL depression - Abstract
Purpose: Chronic inflammation is one of the key mechanisms of depression. Wenyang-Tianjin-Jie Decoction (WTJD) is an effective antidepressant found in the course of diagnosis and treatment, but the mechanism of therapeutic effect is not clear. The study aimed to evaluate the efficacy of WTJD in the kidney yang deficiency (KYD) type of depression rats and reveal its mechanisms. Materials and Methods: We selected forty 6-week-old male Sprague-Dawley rats for the study. We established a KYD [Phellodendron amurense Rupr (Huangbai) solution oral gavage and 4°C environments; 8 weeks] type of depression (chronic unpredictable mild stimulus; 6 weeks) rat model first. After successful modeling, we used WTJD or fluoxetine on rats for 3 weeks. Then we evaluated the depression and KYD behavior. Finally, we observed the expression of key inflammatory factors and proteins in peripheral blood and hippocampus, and further investigated the immune balance of Th17/Treg and Th1/Th2 cells and the activity of their main regulatory pathways JAK2/STAT3 and TLR4/TRAF6/NF-κB. Results: The imbalance of Th17/Treg and Th1/Th2 cells in rats were related to KYD and depressive symptoms. Through this study, we found that WTJD can inhibit the activity of JAK2/STAT3 and TLR4/TRAF6/NF-κB pathways, balance Th17/Treg and Th1/Th2 cell homeostasis, regulate the levels of inflammatory factors in the hippocampus and peripheral blood, and reverse KYD and depression. Conclusion: This study confirmed that WTJD had a reliable effect on depression rats with KYD, and its mechanism was to regulate the immune homeostasis of hippocampal T cells and related inflammatory factors to improve KYD and depression symptoms in rats. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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22. Wnt/β-catenin signaling components and mechanisms in bone formation, homeostasis, and disease.
- Author
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Hu, Lifang, Chen, Wei, Qian, Airong, and Li, Yi-Ping
- Subjects
WNT signal transduction ,BONE growth ,HOMEOSTASIS ,WNT proteins ,CATENINS ,CELL receptors ,CELLULAR signal transduction ,ADULT development - Abstract
Wnts are secreted, lipid-modified proteins that bind to different receptors on the cell surface to activate canonical or non-canonical Wnt signaling pathways, which control various biological processes throughout embryonic development and adult life. Aberrant Wnt signaling pathway underlies a wide range of human disease pathogeneses. In this review, we provide an update of Wnt/β-catenin signaling components and mechanisms in bone formation, homeostasis, and diseases. The Wnt proteins, receptors, activators, inhibitors, and the crosstalk of Wnt signaling pathways with other signaling pathways are summarized and discussed. We mainly review Wnt signaling functions in bone formation, homeostasis, and related diseases, and summarize mouse models carrying genetic modifications of Wnt signaling components. Moreover, the therapeutic strategies for treating bone diseases by targeting Wnt signaling, including the extracellular molecules, cytosol components, and nuclear components of Wnt signaling are reviewed. In summary, this paper reviews our current understanding of the mechanisms by which Wnt signaling regulates bone formation, homeostasis, and the efforts targeting Wnt signaling for treating bone diseases. Finally, the paper evaluates the important questions in Wnt signaling to be further explored based on the progress of new biological analytical technologies. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
23. Confocal Raman imaging reveals the impact of retinoids on human breast cancer via monitoring the redox status of cytochrome c.
- Author
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Surmacki, Jakub Maciej and Abramczyk, Halina
- Subjects
RETINOIDS ,BREAST cancer ,FLUORESCENCE resonance energy transfer ,OXIDATION-reduction reaction ,VITAMIN A ,IRON in the body ,CYTOCHROME c ,RAMAN microscopy ,HOMEOSTASIS - Abstract
This paper expands the current state of knowledge on impact of retinoids on redox status of cytochrome c in cancers. Little is known how the expression of cytochromes may influence the development of cancers. We studied the effect of the redox status of the central iron ion in heme of cytochrome c. We determined the redox status of the iron ion in cytochrome c in mitochondria, cytoplasm, lipid droplets, and endoplasmic reticulum of the human breast cancer cells by Raman imaging. We incubated human breast adenocarcinoma cells (SK-BR-3) with retinoic acid, retinol and retinyl ester (palmitate) at concentration of 50 μM for 24 h. We recorded the Raman spectra and images of human breast cancer in vitro SK-BR-3 cells receiving redox stimuli by retinoic acid, retinol and retinyl ester (palmitate). The paper provides evidence that retinoic acid and retinol are pivotally important for mitochondrial energy homeostasis by controlling the redox status of cytochrome c in the electron transport chain controlling oxidative phosphorylation and apoptosis. We discussed the role of retinoids in metabolism and signaling of cancer cells. The paper provides experimental support for theoretical hypothesis how retinoic acid/retinol catalyse resonance energy transfer reactions and controls the activation/inactivation cycle of protein kinase PKCδ. [ABSTRACT FROM AUTHOR]
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- 2023
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24. The role of arbuscular mycorrhizal fungi in micronutrient homeostasis and cadmium uptake and transfer in rice under different flooding intensities.
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Xu Y, Lambers H, Feng J, Tu Y, Peng Z, and Huang J
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- Soil chemistry, Oryza metabolism, Oryza microbiology, Cadmium metabolism, Mycorrhizae physiology, Soil Pollutants metabolism, Homeostasis, Zinc metabolism, Floods, Iron metabolism, Plant Roots microbiology, Plant Roots metabolism, Micronutrients metabolism
- Abstract
Flooding intensity significantly alters the availability of iron (Fe), zinc (Zn), and cadmium (Cd) in paddy soil. However, the influence of arbuscular mycorrhizal fungi (AMF) on the uptake and transfer of Cd and micronutrients (Fe and Zn) under Cd stress in varying flooding conditions is not well understood. A pot experiment was conducted to investigate the micronutrient homeostasis and Cd uptake and transfer in rice cultivated in Cd-contaminated soil with AMF inoculation under continuous and intermittent flooding conditions. Compared to non-inoculation controls, mycorrhizal inoculation decreased Cd concentration in rice plants under continuous and intermittent flooding, and improved grain yield by 39.2 % for early season rice and 21.1 % for late season rice under continuous flooding. Mycorrhizal inoculation balanced the availability of Zn and Fe and decreased the availability of Cd in soil, lowering the ratios of soil-available Cd to both soil-available Zn and soil Fe
2+ . These changes led to a redistribution of Zn and Fe concentrations in rice, thereby reducing Cd acquisition in a soil-rice system. Structural equation model (SEM) analysis revealed that mycorrhizal inoculation had a strong direct negative effect on the expression of Zn and Fe-related genes OsNRAMP1, OsIRT1, and OsIRT2 in the roots of rice, which in turn directly affected root Cd concentration. Furthermore, mycorrhizal colonization decreased Cd transfer coefficients from leaves to grains under continuous flooding and from nodes and leaves to grains under intermittent flooding. In the nodes, the Fe concentration and the expression of genes OsIRT1 and OsHMA2 were associated with Cd transfer from the nodes to grains. Similarly, in the leaves, the expression of genes OsZIP1 and OsMTP1 corresponded with Cd transfer from leaves to grains. This study provides insights into the role of AMF in affecting micronutrient concentrations and Cd uptake in rice under varying flooding conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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25. Association of urinary glyphosate levels with iron homeostasis among a representative sample of US adults: NHANES 2013-2018.
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Chu PL, Wang CS, Wang C, and Lin CY
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- Humans, Male, Adult, Female, Middle Aged, United States, Young Adult, Adolescent, Aged, Child, Child, Preschool, Ferritins blood, Transferrin metabolism, Glyphosate, Glycine analogs & derivatives, Glycine urine, Iron blood, Iron urine, Homeostasis drug effects, Herbicides, Nutrition Surveys
- Abstract
Purpose: Glyphosate and glyphosate-based herbicides (GBH), widely used globally, were initially considered harmless to humans. Experimental studies have suggested that these substances can disrupt iron homeostasis by interfering with iron uptake or triggering inflammatory responses. However, their potential impact on human iron homeostasis remains underexplored., Approach and Results: We analyzed data from 5812 participants aged three and older from the 2013 to 2018 NHANES. We investigated the relationships between urinary glyphosate levels, oral iron intake, and markers of iron homeostasis, including serum iron, unsaturated iron-binding capacity (UIBC), total iron-binding capacity (TIBC), transferrin saturation, ferritin, and transferrin receptor. Higher urinary glyphosate levels were positively associated with oral iron intake (β = 1.310, S.E. = 0.382, P = 0.001). A one-unit increase in the natural logarithm (ln)-glyphosate was associated with lower serum iron (β = - 4.236, 95 % CI = - 6.432 to - 2.039, P < 0.001) and ferritin (β = - 9.994, 95 % CI = - 17.342 to - 2.647, P = 0.009), and higher UIBC (β = 5.431, 95 % CI = 1.061-9.800, P = 0.018) and transferrin receptor levels (β = 0.139, 95 % CI = 0.015-0.263, P = 0.029). Increasing glyphosate exposure was associated with significant decreases in serum iron and ferritin across exposure quintiles (trend P-values = 0.003 and 0.018, respectively)., Conclusions: Higher glyphosate exposure is associated with reduced iron availability, suggesting potential disruptions in iron absorption. These findings underscore the need for further research into the health implications of glyphosate exposure on iron homeostasis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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26. The low-density lipoprotein receptor contributes to carotenoid homeostasis by regulating tissue uptake and fecal elimination.
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Miller AP, Monroy WC, Soria G, and Amengual J
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- Animals, Female, Male, Mice, Adipose Tissue metabolism, Mice, Knockout, Carotenoids metabolism, Feces chemistry, Homeostasis, Liver metabolism, Mice, Inbred C57BL, Receptors, LDL metabolism
- Abstract
Objective: Carotenoids are lipophilic plant molecules with antioxidant properties. Some carotenoids such as β-carotene also serve as vitamin A precursors, playing a key role in human health. Carotenoids are transported in lipoproteins with other lipids such as cholesterol, however, the mechanisms responsible for carotenoid storage in tissues and their non-enzymatic elimination remain relatively unexplored. The goal of this study was to examine the contribution of the low-density lipoprotein receptor (LDLR) in the bodily distribution and disposal of carotenoids., Methods: We employed mice lacking one or both carotenoid-cleaving enzymes as suitable models for carotenoid accumulation. We examined the contribution of LDLR in carotenoid distribution by crossbreeding these mice with Ldlr-/- mice or overexpressing LDLR in the liver., Results: Our results show that LDLR plays a dual role in carotenoid homeostasis by simultaneously favoring carotenoid storage in the liver and adipose tissue while facilitating their fecal elimination., Conclusions: Our results highlight a novel role of the LDLR in carotenoid homeostasis, and unveil a previously unrecognized disposal pathway for these important bioactive molecules., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)
- Published
- 2024
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27. The toxic effects of tetracycline exposure on the physiological homeostasis of the gut-liver axis in grouper.
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Duan Y, Yang Y, Li H, Zhang Z, Chen X, Xiao M, and Nan Y
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- Animals, Bass physiology, Anti-Bacterial Agents toxicity, Oxidative Stress drug effects, Liver drug effects, Homeostasis drug effects, Water Pollutants, Chemical toxicity, Tetracycline toxicity, Gastrointestinal Microbiome drug effects
- Abstract
Antibiotic residues, such as tetracycline (TET), in aquatic environments have become a global concern. The liver and gut are important for immunity and metabolism in aquatic organisms. In this study, juvenile groupers were subjected to 1 and 100 μg/L TET for 14 days, and the physiological changes of these fish were evaluated from the perspective of gut-liver axis. After TET exposure, the liver showed histopathology, lipid accumulation, and the elevated ALT activity. An oxidative stress response was induced in the liver and the metabolic pattern was disturbed, especially pyrimidine metabolism. Further, intestinal health was also affected, including the damaged intestinal mucosa, the decreased mRNA expression levels of tight junction proteins (ZO-1, Occludin, and Claudin-3), along with the increased gene expression levels of inflammation (IL-1β, IL-8, TNF-α) and apoptosis (Casp-3 and p53). The diversity of intestinal microbes increased and the community composition was altered, and several beneficial bacteria (Lactobacillus, Bacteroidales S24-7 group, and Romboutsia) and harmful (Aeromonas, Flavobacterium, and Nautella) exhibited notable correlations with hepatic physiological indicators and metabolites. These results suggested that TET exposure can adversely affect the physiological homeostasis of groupers through the gut-liver axis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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28. Ferroptosis: Regulatory mechanisms and potential targets for bone metabolism: A review.
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Zhang Y, Hu K, Shang Z, Yang X, and Cao L
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- Humans, Bone and Bones metabolism, Signal Transduction physiology, Reactive Oxygen Species metabolism, Osteoblasts metabolism, Lipid Peroxidation, Osteoporosis metabolism, Osteoclasts metabolism, Bone Diseases metabolism, Ferroptosis physiology, Homeostasis physiology
- Abstract
Bone homeostasis is a homeostasis process constructed by osteoblast bone formation and osteoclast bone resorption. Bone homeostasis imbalance and dysfunction are the basis for the development of various orthopedic diseases such as osteoporosis, osteoarthritis, and steroid-induced avascular necrosis of femoral head. Previous studies have demonstrated that ferroptosis can induce lipid peroxidation through the generation of reactive oxygen species, activate a number of signaling pathways, and participate in the regulation of osteoblast bone formation and osteoclast bone resorption, resulting in bone homeostasis imbalance, which is an important factor in the pathogenesis of many orthopedic diseases, but the mechanism of ferroptosis is still unknown. In recent years, it has been found that, in addition to iron metabolism and intracellular antioxidant system imbalance, organelle dysfunction is also a key factor affecting ferroptosis. This paper takes this as the starting point, reviews the latest literature reports at home and abroad, elaborates the pathogenesis and regulatory pathways of ferroptosis and the relationship between ferroptosis and various organelles, and summarizes the mechanism by which ferroptosis mediates bone homeostasis imbalance, with the aim of providing new directions for the research related to ferroptosis and new ideas for the prevention and treatment of bone and joint diseases., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2024
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29. Impacts of prenatal environmental exposures on fetal-placental-maternal bile acid homeostasis and long-term health in offspring.
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Huang W, Hu W, Fang M, Zhang Q, Zhang Y, and Wang H
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- Pregnancy, Female, Humans, Fetus metabolism, Animals, Prenatal Exposure Delayed Effects, Maternal Exposure adverse effects, Fetal Development, Environmental Exposure adverse effects, Bile Acids and Salts metabolism, Bile Acids and Salts blood, Homeostasis, Maternal-Fetal Exchange, Placenta metabolism
- Abstract
During pregnancy, the maternal body undergoes a series of adaptative physiological changes, leading to a slight increase in serum bile acid (BA) levels. Although the fetal liver can synthesize BAs since the first trimester through the alternative pathway, the BA metabolic system is immature in the fetus. Compared to adults, the fetus has a distinct composition of BA pool and limited expression of BA synthesis enzymes and transporters. Besides, the "enterohepatic circulation" of BAs is absent in fetus. Thus, fetal BAs need to be transported to the mother through the placenta for further metabolism and excretion, and maternal BAs can also be transported to the fetus. That is what we call the "fetal-placental-maternal BA circulation". Various BA transporters and nuclear receptors are essential for maintaining the balance of this BA circulation to ensure normal fetal development. However, prenatal adverse environments can alter fetal BA metabolism, resulting in intrauterine developmental abnormalities and susceptibility to a variety of adult chronic diseases. This review summarizes the current understanding of the fetal-placental-maternal BA circulation and discusses the effects of prenatal adverse environments on this particular BA circulation, aiming to provide a theoretical basis for exploring early prevention and treatment strategies for BA metabolism-associated adverse pregnancy outcomes and long-term impairments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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30. Adenosine protects cardiomyocytes against acrolein-induced cardiotoxicity by enhancing mitochondrial homeostasis, antioxidant defense, and autophagic flux via ERK-activated FoxO1 upregulation.
- Author
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Gao J, Liu X, Wang M, Zeng X, Wang Z, Wang Y, Lou J, Liu J, and Zhao L
- Subjects
- Animals, Rats, Cardiotoxicity, Apoptosis drug effects, Oxidative Stress drug effects, Forkhead Box Protein O1 metabolism, Cell Line, Extracellular Signal-Regulated MAP Kinases metabolism, Acrolein toxicity, Myocytes, Cardiac drug effects, Myocytes, Cardiac metabolism, Autophagy drug effects, Antioxidants pharmacology, Antioxidants metabolism, Adenosine, Mitochondria drug effects, Mitochondria metabolism, Up-Regulation drug effects, Homeostasis drug effects
- Abstract
Acrolein is a ubiquitous gaseous air pollutant and endogenous toxicant, which poses strong risk for oxidative stress-related diseases such as cardiovascular disease. Adenosine has been identified as potential therapeutic agent for age-related cardiovascular disease, while the molecular mechanisms underlying its cardioprotection remain elusive. In the present study, we investigated the myocardial protective effects and the mechanism of adenosine on acrolein-induced toxicity in H9c2 cells and primary neonatal rat cardiomyocytes. We found that acrolein caused apoptosis of cardiomyocytes resulting from oxidative damage, autophagy defect, and mitochondrial dysfunction, as evidenced by loss of mitochondrial membrane potential, impairment of mitochondrial biogenesis, dynamics, and oxidative phosphorylation, decrease of mitochondrial deoxyribonucleic acid (mtDNA) copy number and adenosine 5'-triphosphate (ATP) production. Adenosine pretreatment protected against acrolein-induced cardiotoxicity by maintaining mitochondrial homeostasis, activating the phase II detoxifying enzyme system, promoting autophagic flux, and alleviating mitochondrial-dependent apoptosis. We further demonstrated that the up-regulation of forkhead box protein O1 (FoxO1) mediated by extracellular regulated protein kinases (ERK) activation contributes to the cardioprotection of adenosine. These results expand the application of adenosine in cardioprotection to preventing myocardial damages induced by environmental pollutant acrolein exposure, and uncover the adenosine-ERK-FoxO1 axis as the underlying mechanism mediating the protection of mitochondrial homeostasis, Nrf2-mediated antioxidant defense and autophagic flux, shedding light on the better understanding about the pathological mechanism of cardiovascular disease caused by environmental pollutants and applications of adenosine in cardioprotection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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31. Collagen-based hydrogels induce hyaline cartilage regeneration by immunomodulation and homeostasis maintenance.
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Gao Y, Wang J, Dai W, Li S, Liu Q, Zhao X, Fu W, Xiao Y, Guo L, Fan Y, and Zhang X
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- Animals, Chondrogenesis drug effects, Mice, Immunomodulation drug effects, Chondrocytes drug effects, Chondrocytes metabolism, Collagen Type I metabolism, Cell Differentiation drug effects, Tissue Scaffolds chemistry, Macrophages drug effects, Macrophages metabolism, Hydrogels chemistry, Hydrogels pharmacology, Regeneration drug effects, Hyaline Cartilage drug effects, Homeostasis drug effects, Hyaluronic Acid chemistry, Hyaluronic Acid pharmacology
- Abstract
Type I collagen (Col I) and hyaluronic acid (HA), derived from the extracellular matrix (ECM), have found widespread application in cartilage tissue engineering. Nevertheless, the potential of cell-free collagen-based scaffolds to induce in situ hyaline cartilage regeneration and the related mechanisms remain undisclosed. Here, we chose Col I and HA to construct Col I hydrogel and Col I-HA composite hydrogel with similar mechanical properties, denoted as Col and ColHA, respectively. Their potential to induce cartilage regeneration was investigated. The results revealed that collagen-based hydrogels could regenerate hyaline cartilage without any additional cells or growth factors. Notably, ColHA hydrogel stood out in this regard. It elicited a moderate activation, recruitment, and reprogramming of macrophages, thus efficiently mitigating local inflammation. Additionally, ColHA hydrogel enhanced stem cell recruitment, facilitated their chondrogenic differentiation, and inhibited chondrocyte fibrosis, hypertrophy, and catabolism, thereby preserving cartilage homeostasis. This study augments our comprehension of cartilage tissue induction theory by enriching immune-related mechanisms, offering innovative prospects for the design of cartilage defect repair scaffolds. STATEMENT OF SIGNIFICANCE: The limited self-regeneration ability and post-injury inflammation pose significant challenges to articular cartilage repair. Type I collagen (Col I) and hyaluronic acid (HA) are extensively used in cartilage tissue engineering. However, their specific roles in cartilage regeneration remain poorly understood. This study aimed to elucidate the functions of Col I and Col I-HA composite hydrogels (ColHA) in orchestrating inflammatory responses and promoting cartilage regeneration. ColHA effectively activated and recruited macrophages, reprogramming them from an M1 to an M2 phenotype, thus alleviating local inflammation. Additionally, ColHA facilitated stem cell homing, induced chondrogenesis, and concurrently inhibited fibrosis, hypertrophy, and catabolism, collectively contributing to the maintenance of cartilage homeostasis. These findings underscore the clinical potential of ColHA for repairing cartilage defects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2024
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32. Intracellular peroxynitrite perturbs redox balance, bioenergetics, and Fe-S cluster homeostasis in Mycobacterium tuberculosis.
- Author
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Dewan A, Jain C, Das M, Tripathi A, Sharma AK, Singh H, Malhotra N, Seshasayee ASN, Chakrapani H, and Singh A
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- Humans, Nitric Oxide metabolism, Oxidative Stress, Mycobacterium smegmatis metabolism, Mycobacterium smegmatis genetics, Mycobacterium smegmatis drug effects, Superoxides metabolism, Macrophages metabolism, Macrophages microbiology, Tuberculosis microbiology, Tuberculosis metabolism, Mycobacterium tuberculosis metabolism, Mycobacterium tuberculosis genetics, Mycobacterium tuberculosis drug effects, Peroxynitrous Acid metabolism, Oxidation-Reduction, Homeostasis, Energy Metabolism, Iron-Sulfur Proteins metabolism, Iron-Sulfur Proteins genetics
- Abstract
The ability of Mycobacterium tuberculosis (Mtb) to tolerate nitric oxide (
• NO) and superoxide (O2 •- ) produced by phagocytes contributes to its success as a human pathogen. Recombination of• NO and O2 •- generates peroxynitrite (ONOO- ), a potent oxidant produced inside activated macrophages causing lethality in diverse organisms. While the response of Mtb toward• NO and O2 •- is well established, how Mtb responds to ONOO- remains unclear. Filling this knowledge gap is important to understand the persistence mechanisms of Mtb during infection. We synthesized a series of compounds that generate both• NO and O2 . RNA-sequencing with Mtb revealed that CJ067 induces antioxidant machinery, sulphur metabolism, metal homeostasis, and a 4Fe-4S cluster repair pathway (suf operon). CJ067 impaired the activity of the 4Fe-4S cluster-containing TCA cycle enzyme, aconitase, and diminished bioenergetics of Mtb. Work with Mtb strains defective in SUF and IscS involved in Fe-S cluster biogenesis pathways showed that both systems cooperatively protect Mtb from intracellular ONOO•- , which should combine to produce ONOO- and targeting Fe-S cluster homeostasis is expected to promote iNOS-dependent host immunity against tuberculosis (TB).- levels. CJ067-exposed Mtb strains, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) clinical isolates, exhibited dose-dependent, long-lasting oxidative stress and growth inhibition. In contrast, Mycobacterium smegmatis (Msm), a fast-growing, non-pathogenic mycobacterial species, maintained redox balance and growth in response to intracellular ONOO- . RNA-sequencing with Mtb revealed that CJ067 induces antioxidant machinery, sulphur metabolism, metal homeostasis, and a 4Fe-4S cluster repair pathway (suf operon). CJ067 impaired the activity of the 4Fe-4S cluster-containing TCA cycle enzyme, aconitase, and diminished bioenergetics of Mtb. Work with Mtb strains defective in SUF and IscS involved in Fe-S cluster biogenesis pathways showed that both systems cooperatively protect Mtb from intracellular ONOO- in vitro and inducible nitric oxide synthase (iNOS)-dependent growth inhibition during macrophage infection. Thus, Mtb is uniquely sensitive to intracellular ONOO- and targeting Fe-S cluster homeostasis is expected to promote iNOS-dependent host immunity against tuberculosis (TB)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2024
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33. Theabrownin from Pu-erh Tea Improves DSS-Induced Colitis via Restoring Gut Homeostasis and Inhibiting TLR2&4 Signaling Pathway.
- Author
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Zhao L, Zhao C, Miao Y, Lei S, Li Y, Gong J, and Peng C
- Subjects
- Animals, Mice, Male, Catechin pharmacology, Disease Models, Animal, Gastrointestinal Microbiome drug effects, Colitis, Ulcerative drug therapy, Colitis, Ulcerative chemically induced, Colitis drug therapy, Colitis chemically induced, Intestinal Mucosa drug effects, Intestinal Mucosa metabolism, Cytokines metabolism, NF-kappa B metabolism, Toll-Like Receptor 2 metabolism, Signal Transduction drug effects, Dextran Sulfate, Mice, Inbred C57BL, Toll-Like Receptor 4 metabolism, Tea chemistry, Homeostasis drug effects
- Abstract
Background: Theabrownin (TB) is a dark brown pigment from Pu-erh tea or other dark teas. It is formed by further oxidization of theaflavins and thearubigins, in combination with proteins, polysaccharides, and caffeine etc. TB is a characteristic ingredient and bioactive substance of Pu-erh tea. However, the effects of TB on ulcerative colitis (UC) remains unclear., Purpose: This study aims to elucidate the mechanism of TB on UC in terms of recovery of intestinal homeostasis and regulation of toll-like receptor (TLR) 2&4 signaling pathway., Methods: The colitis models were established by administering 5% dextran sulfate sodium (DSS) to C57BL/6 mice for 5 days to evaluate the therapeutic and preventive effects of TB on UC. Mesalazine was used as a positive control. H&E staining, complete blood count, enzyme-linked immunosorbent assay, immunohistochemistry, flow cytometry, and 16S rRNA sequencing were employed to assess histological changes, blood cells analysis, content of cytokines, expression and distribution of mucin (MUC)2 and TLR2&4, differentiation of CD4
+ T cells in lamina propria, and changes in intestinal microbiota, respectively. Western blot was utilized to study the relative expression of tight junction proteins and the key proteins in TLR2&4-mediated MyD88-dependent MAPK, NF-κB, and AKT signaling pathways., Results: TB outstanding alleviated colitis, inhibited the release of pro-inflammatory cytokines, reduced white blood cells while increasing red blood cells, hemoglobin, and platelets. TB increased the expression of occludin, claudin-1 and MUC2, effectively restored intestinal barrier function. TB also suppressed differentiation of Th1 and Th17 cells in the colon's lamina propria, increased the fraction of Treg cells, and promoted the balance of Treg/Th17 to tilt towards Tregs. Moreover, TB increased the Firmicutes to Bacteroides (F/B) ratio, as well as the abundance of Akkermansia, Muribaculaceae, and Eubacterium_coprostanoligenes_group at the genus level. In addition, TB inhibited the activation of TLR2&4-mediated MAPK, NF-κB, and AKT signaling pathways in intestinal epithelial cells of DSS-induced mice., Conclusion: TB acts in restoring intestinal homeostasis and anti-inflammatory in DSS-induced UC, and exhibiting a preventive effect after long-term use. In a word, TB is a promising beverage, health product and food additive for UC., Competing Interests: Declaration of competing interest The authors declare that they have no known conflict of interest or individual connections that could have appeared to impact the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)- Published
- 2024
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34. Oxidative stress and the multifaceted roles of ATM in maintaining cellular redox homeostasis.
- Author
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Lee JH
- Subjects
- Humans, Ataxia Telangiectasia metabolism, Ataxia Telangiectasia genetics, Ataxia Telangiectasia pathology, Animals, DNA Damage, Antioxidants metabolism, Mitochondria metabolism, Ataxia Telangiectasia Mutated Proteins metabolism, Ataxia Telangiectasia Mutated Proteins genetics, Oxidative Stress, Oxidation-Reduction, Homeostasis, Reactive Oxygen Species metabolism
- Abstract
The ataxia telangiectasia mutated (ATM) protein kinase is best known as a master regulator of the DNA damage response. However, accumulating evidence has unveiled an equally vital function for ATM in sensing oxidative stress and orchestrating cellular antioxidant defenses to maintain redox homeostasis. ATM can be activated through a non-canonical pathway involving intermolecular disulfide crosslinking of the kinase dimers, distinct from its canonical activation by DNA double-strand breaks. Structural studies have elucidated the conformational changes that allow ATM to switch into an active redox-sensing state upon oxidation. Notably, loss of ATM function results in elevated reactive oxygen species (ROS) levels, altered antioxidant profiles, and mitochondrial dysfunction across multiple cell types and tissues. This oxidative stress arising from ATM deficiency has been implicated as a central driver of the neurodegenerative phenotypes in ataxia-telangiectasia (A-T) patients, potentially through mechanisms involving oxidative DNA damage, PARP hyperactivation, and widespread protein aggregation. Moreover, defective ATM oxidation sensing disrupts transcriptional programs and RNA metabolism, with detrimental impacts on neuronal homeostasis. Significantly, antioxidant therapy can ameliorate cellular and organismal abnormalities in various ATM-deficient models. This review synthesizes recent advances illuminating the multifaceted roles of ATM in preserving redox balance and mitigating oxidative insults, providing a unifying paradigm for understanding the complex pathogenesis of A-T disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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35. Heterogeneity effects of bisphenol A and its substitute, fluorene-9-bisphenol, on intestinal homeostasis.
- Author
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Peng J, Cao S, Hu Z, Zhu J, Zhu Y, Sheng X, Cai Z, Bai R, Xiong X, and Sheng J
- Subjects
- Animals, Mice, Intestinal Mucosa drug effects, Intestinal Mucosa metabolism, Organoids drug effects, Cell Differentiation drug effects, Cell Proliferation drug effects, Phenols toxicity, Benzhydryl Compounds toxicity, Fluorenes toxicity, Homeostasis drug effects
- Abstract
Bisphenol A (BPA) and its substitute fluorene-9-bisphenol (BHPF) are used in consumer products; however, their toxic effects on intestinal epithelium remain largely unknown. In this study, we combined intestinal organoids and single-cell RNA sequencing to investigate the impact of BPA and BHPF exposure on intestinal cell composition, differentiation, and function. Both compounds inhibited the growth of small intestinal organoids, with BHPF exhibiting a more potent inhibitory effect. BPA and BHPF did not significantly alter the overall cell type composition; however, they led to different alterations in cell-cell communications. Gene Ontology enrichment analysis showed that BPA and BHPF exposures affected various biological processes, such as glutathione transferase activity, antioxidant activity, and lipid metabolism, in cell type-specific and compound-dependent manners. Trajectory analysis demonstrated that BPA and BHPF altered the differentiation trajectory of the intestinal cells. To further connect the cellular mechanism to the phenotypic impact in vivo, we constructed a mouse model exposed to BPA or BHPF and observed significant alterations in intestinal morphology, including reduced crypt depth and villus length and impaired stem cell proliferation and self-renewal. These results provide novel insights into the cell type-specific effects of BPA and BHPF on the intestinal epithelium and highlight the potential risks of exposure to these compounds. Our findings underscore the importance of evaluating the safety of BPA substitutes and contribute to a better understanding of the effects of environmental chemicals on gut health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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36. Tanycytic transcytosis inhibition disrupts energy balance, glucose homeostasis and cognitive function in male mice.
- Author
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Duquenne M, Deligia E, Folgueira C, Bourouh C, Caron E, Pfrieger F, Schwaninger M, Nogueiras R, Annicotte JS, Imbernon M, and Prévot V
- Subjects
- Animals, Male, Mice, Cognition drug effects, Leptin metabolism, Mice, Inbred C57BL, Hypothalamus metabolism, Obesity metabolism, Homeostasis, Energy Metabolism, Glucose metabolism, Ependymoglial Cells metabolism
- Abstract
Objectives: In Western society, high-caloric diets rich in fats and sugars have fueled the obesity epidemic and its related disorders. Disruption of the body-brain communication, crucial for maintaining glucose and energy homeostasis, arises from both obesogenic and genetic factors, leading to metabolic disorders. Here, we investigate the role of hypothalamic tanycyte shuttles between the pituitary portal blood and the third ventricle cerebrospinal fluid in regulating energy balance., Methods: We inhibited vesicle-associated membrane proteins (VAMP1-3)-mediated release in tanycytes by expressing the botulinum neurotoxin type B light chain (BoNT/B) in a Cre-dependent manner in tanycytes. This was achieved by injecting either TAT-Cre in the third ventricle or an AAV1/2 expressing Cre under the control of the tanycyte-specific promoter iodothyronine deiodinase 2 into the lateral ventricle of adult male mice., Results: In male mice fed a standard diet, targeted expression of BoNT/B in adult tanycytes blocks leptin transport into the mediobasal hypothalamus and results in normal-weight central obesity, including increased food intake, abdominal fat deposition, and elevated leptin levels but no marked change in body weight. Furthermore, BoNT/B expression in adult tanycytes promotes fatty acid storage, leading to glucose intolerance and insulin resistance. Notably, these metabolic disturbances occur despite a compensatory increase in insulin secretion, observed both in response to exogenous glucose boluses in vivo and in isolated pancreatic islets. Intriguingly, these metabolic alterations are associated with impaired spatial memory in BoNT/B-expressing mice., Conclusions: These findings underscore the central role of tanycytes in brain-periphery communication and highlight their potential implication in the age-related development of type 2 diabetes and cognitive decline. Our tanycytic BoNT/B mouse model provides a robust platform for studying how these conditions progress over time, from prediabetic states to full-blown metabolic and cognitive disorders, and the mechanistic contribution of tanycytes to their development. The recognition of the impact of tanycytic transcytosis on hormone transport opens new avenues for developing targeted therapies that could address both metabolic disorders and their associated cognitive comorbidities, which often emerge or worsen with advancing age., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)
- Published
- 2024
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37. Metastatic breast cancer cells are metabolically reprogrammed to maintain redox homeostasis during metastasis.
- Author
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Biondini M, Lehuédé C, Tabariès S, Annis MG, Pacis A, Ma EH, Tam C, Hsu BE, Audet-Delage Y, Abu-Thuraia A, Girondel C, Sabourin V, Totten SP, de Sá Tavares Russo M, Bridon G, Avizonis D, Guiot MC, St-Pierre J, Ursini-Siegel J, Jones R, and Siegel PM
- Subjects
- Female, Humans, Animals, Mice, Cell Line, Tumor, Glycolysis, Neoplasm Metastasis, Gene Expression Regulation, Neoplastic, Tumor Microenvironment, Breast Neoplasms pathology, Breast Neoplasms metabolism, Breast Neoplasms genetics, Oxidation-Reduction, Glutathione metabolism, Reactive Oxygen Species metabolism, Liver Neoplasms metabolism, Liver Neoplasms pathology, Liver Neoplasms secondary, Liver Neoplasms genetics, Glutamate-Cysteine Ligase metabolism, Glutamate-Cysteine Ligase genetics, Homeostasis
- Abstract
Metabolic rewiring is essential for tumor growth and progression to metastatic disease, yet little is known regarding how cancer cells modify their acquired metabolic programs in response to different metastatic microenvironments. We have previously shown that liver-metastatic breast cancer cells adopt an intrinsic metabolic program characterized by increased HIF-1α activity and dependence on glycolysis. Here, we confirm by in vivo stable isotope tracing analysis (SITA) that liver-metastatic breast cancer cells retain a glycolytic profile when grown as mammary tumors or liver metastases. However, hepatic metastases exhibit unique metabolic adaptations including elevated expression of genes involved in glutathione (GSH) biosynthesis and reactive oxygen species (ROS) detoxification when compared to mammary tumors. Accordingly, breast-cancer-liver-metastases exhibited enhanced de novo GSH synthesis. Confirming their increased capacity to mitigate ROS-mediated damage, liver metastases display reduced levels of 8-Oxo-2'-deoxyguanosine. Depletion of the catalytic subunit of the rate-limiting enzyme in glutathione biosynthesis, glutamate-cysteine ligase (GCLC), strongly reduced the capacity of breast cancer cells to form liver metastases, supporting the importance of these distinct metabolic adaptations. Loss of GCLC also affected the early steps of the metastatic cascade, leading to decreased numbers of circulating tumor cells (CTCs) and impaired metastasis to the liver and the lungs. Altogether, our results indicate that GSH metabolism could be targeted to prevent the dissemination of breast cancer cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
- Published
- 2024
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38. Different impact of short-term and long-term hindlimb disuse on bone homeostasis.
- Author
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Gao M, Dong C, Chen Z, Jiang R, Shaw P, Gao W, and Sun Y
- Subjects
- Animals, Mice, Osteogenesis genetics, Male, Mice, Inbred C57BL, X-Ray Microtomography, Osteoporosis genetics, Bone and Bones metabolism, Bone Density, Hindlimb, Hindlimb Suspension, Homeostasis
- Abstract
Disuse osteoporosis is one of the major problems of bone health which commonly occurs in astronauts during long-term spaceflight and bedridden patients. However, the mechanisms underlying such mechanical unloading induced bone loss have not been fully understood. In this study, we employed hindlimb-unloading mice models with different length of tail suspension to investigate if the bone loss was regulated by distinct factors under different duration of disuse. Our micro-CT results showed more significant decrease of bone mass in 6W (6-week) tail-suspension mice compared to the 1W (1-week) tail-suspension ones, as indicated by greater reduction of BV/TV, Tb.N, B.Ar/T.Ar and Ct.Th. RNA-sequencing results showed significant effects of hindlimb disuse on cell locomotion and immune system process which could cause bone loss.Real-time quantitative PCR results indicated a greater number of bone formation related genes that were downregulated in short-term tail-suspension mice compared to the long-term ones. It is, thus, suggested while sustained hindlimb unloading continuously contributes to bone loss, molecular regulation of bone homeostasis tends to reach a balance during this process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
39. Maintaining calcium homeostasis as a strategy to alleviate nephrotoxicity caused by evodiamine.
- Author
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Yang CQ, Lai CC, Pan JC, Gao J, Shen BY, Ru Y, Shen X, Liu Y, Shen NN, Li BW, Wang YG, and Gao Y
- Subjects
- Animals, Mice, Male, TRPV Cation Channels metabolism, Calcium Chelating Agents pharmacology, Quinazolines toxicity, Quinazolines pharmacology, Homeostasis drug effects, Calcium metabolism, Apoptosis drug effects, Kidney drug effects, Kidney pathology, Evodia chemistry
- Abstract
Evodiamine (EVO), the main active alkaloid in Evodia rutaecarpa, was shown to exert various pharmacological activities, especially anti-tumor. Currently, it is considered a potential anti-cancer drug due to its excellent anti-tumor activity, which unfortunately has adverse reactions, such as the risk of liver and kidney injury, when Evodia rutaecarpa containing EVO is used clinically. In the present study, we aim to clarify the potential toxic target organs and toxicity mechanism of EVO, an active monomer in Evodia rutaecarpa, and to develop mitigation strategies for its toxicity mechanism. Transcriptome analysis and related experiments showed that the PI3K/Akt pathway induced by calcium overload was an important step in EVO-induced apoptosis of renal cells. Specifically, intracellular calcium ions were increased, and mitochondrial calcium ions were decreased. In addition, EVO-induced calcium overload was associated with TRPV1 receptor activation. In vivo TRPV1 antagonist and calcium chelator effects were observed to significantly reduce body weight loss and renal damage in mice due to EVO toxicity. The potential nephrotoxicity of EVO was further confirmed by an in vivo test. In conclusion, TRPV1-mediated calcium overload-induced apoptosis is one of the mechanisms contributing to the nephrotoxicity of EVO due to its toxicity, whereas maintaining body calcium homeostasis is an effective measure to reduce toxicity. These studies suggest that the clinical use of EVO-containing herbal medicines should pay due attention to the changes in renal function of patients as well as the off-target effects of the drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
40. Hydrogel-forming viscous liquid in response to ROS restores the gut mucosal barrier of colitis mice via regulating oxidative redox homeostasis.
- Author
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Shangguan J, Yu F, Ding B, Jiang Z, Wang J, Li D, Chen Y, Zhao Y, Hu S, and Xu H
- Subjects
- Animals, Mice, Reactive Oxygen Species metabolism, Hydrogels chemistry, Hydrogels pharmacology, Mice, Inbred C57BL, Colon pathology, Colon drug effects, Colon metabolism, Viscosity, Hyaluronic Acid chemistry, Hyaluronic Acid pharmacology, Cysteamine pharmacology, Cysteamine chemistry, Superoxide Dismutase metabolism, Male, Hydrogen Peroxide, Cytokines metabolism, Dextran Sulfate, Homeostasis drug effects, Colitis drug therapy, Colitis pathology, Colitis chemically induced, Colitis metabolism, Intestinal Mucosa metabolism, Intestinal Mucosa drug effects, Intestinal Mucosa pathology, Oxidation-Reduction
- Abstract
The disrupted oxidative redox homeostasis plays a critical role in the progress of ulcerative colitis (UC). Herein, hydrogel-forming viscous liquid (HSD) composed of cysteamine-grafted hyaluronic acid (HS) and superoxide dismutase (SOD) has been designed for UC. When the viscous HSD liquid was infused into colitis colon, SOD would convert the pathological superoxide (O
2 ·- ) to hydrogen peroxides (H2 O2 ), which was subsequently scavenged by HS. Accordingly, the sol-gel transition of HSD was initiated by scavenging H2 O2 , enhancing its adhesion toward colitis colon. H2 O2 -treated HSD presented the higher storage modulus and stronger adhesion force toward porcine colon than the untreated HSD. Besides, H2 -treated HSD presented the slower erosion profile in the colitis-mimicking medium (pH 3-5), while its rapid degradation was displayed in physiologic condition (pH7.4). The combination of pH-resistant erosion and ROS-responsive adhesion for HSD rendered it with the specifical retention on the inflamed colonic mucosa of DSS-induced colitis mice. Rectally administrating HSD could effectively hinder the body weight loss, reduce the disease activity index and improve the colonic shorting of DSS-induced colitis mice. Moreover, the pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) were substantially decreased, the colonic epitheliums were well rearranged and the tight junction proteins were greatly recovered after HSD treatment. Besides, HSD also modulated the gut flora, markedly augmenting the abundance of Firmicutes, Barnesiella and Lachnospiraceae. Moreover, HSD treatment could regulate oxidative redox homeostasis via activating Nrf2-HO-1 pathway to reduce ROS and malondialdehyde and upregulate antioxidant enzymes (SOD, GPx and GSH). Collectively, HSD might be a promising therapy for UC treatments. STATEMENT OF SIGNIFICANCE: Herein, a hydrogel-forming viscous liquid (HSD) was designed by cysteamine-grafted hyaluronic acid (HS) and superoxide dismutase (SOD) for UC treatments. When the viscous HSD liquid was infused into a colitis colon, SOD would convert the pathological superoxide to hydrogen peroxides (H2O2), which was subsequently scavenged by HS. Accordingly, the sol-gel transition of HSD was initiated by scavenging H2O2, enhancing its adhesion to the colitis colon. The colonic epitheliums of DSS-induced colitis mice were well rearranged and the tight junction proteins (Zonula-1 and Claudin-5) were greatly recovered after the HSD treatment. Moreover, the HSD treatment could regulate oxidative redox homeostasis via activating the Nrf2-HO-1 pathway to reduce ROS and malondialdehyde and upregulate antioxidant enzymes (SOD, GPx and GSH).2 -treated HSD presented the slower erosion profile in the colitis-mimicking medium (pH 3-5), while its rapid degradation was displayed in physiologic condition (pH7.4). The combination of pH-resistant erosion and ROS-responsive adhesion for HSD rendered it with the specifical retention on the inflamed colonic mucosa of DSS-induced colitis mice. Rectally administrating HSD could effectively hinder the body weight loss, reduce the disease activity index and improve the colonic shorting of DSS-induced colitis mice. Moreover, the pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) were substantially decreased, the colonic epitheliums were well rearranged and the tight junction proteins were greatly recovered after HSD treatment. Besides, HSD also modulated the gut flora, markedly augmenting the abundance of Firmicutes, Barnesiella and Lachnospiraceae. Moreover, HSD treatment could regulate oxidative redox homeostasis via activating Nrf2-HO-1 pathway to reduce ROS and malondialdehyde and upregulate antioxidant enzymes (SOD, GPx and GSH). Collectively, HSD might be a promising therapy for UC treatments. STATEMENT OF SIGNIFICANCE: Herein, a hydrogel-forming viscous liquid (HSD) was designed by cysteamine-grafted hyaluronic acid (HS) and superoxide dismutase (SOD) for UC treatments. When the viscous HSD liquid was infused into a colitis colon, SOD would convert the pathological superoxide to hydrogen peroxides (H2O2), which was subsequently scavenged by HS. Accordingly, the sol-gel transition of HSD was initiated by scavenging H2O2, enhancing its adhesion to the colitis colon. The colonic epitheliums of DSS-induced colitis mice were well rearranged and the tight junction proteins (Zonula-1 and Claudin-5) were greatly recovered after the HSD treatment. Moreover, the HSD treatment could regulate oxidative redox homeostasis via activating the Nrf2-HO-1 pathway to reduce ROS and malondialdehyde and upregulate antioxidant enzymes (SOD, GPx and GSH)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
41. Fe-S cluster homeostasis and beyond: The multifaceted roles of IscR.
- Author
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Mettert EL and Kiley PJ
- Subjects
- Gene Expression Regulation, Bacterial, Transcription Factors metabolism, Transcription Factors genetics, Humans, Escherichia coli metabolism, Escherichia coli genetics, Homeostasis, Iron-Sulfur Proteins metabolism, Iron-Sulfur Proteins genetics, Iron metabolism, Escherichia coli Proteins metabolism, Escherichia coli Proteins genetics
- Abstract
The role of IscR in regulating the transcription of genes involved in Fe-S cluster homeostasis has been well established for the model organism Escherichia coli K12. In this bacterium, IscR coordinates expression of the Isc and Suf Fe-S cluster assembly pathways to meet cellular Fe-S cluster demands shaped by a variety of environmental cues. However, since its initial discovery nearly 25 years ago, there has been growing evidence that IscR function extends well beyond Fe-S cluster homeostasis, not only in E. coli, but in bacteria of diverse lifestyles. Notably, pathogenic bacteria have exploited the ability of IscR to respond to changes in oxygen tension, oxidative and nitrosative stress, and iron availability to navigate their trajectory in their respective hosts as changes in these cues are frequently encountered during host infection. In this review, we highlight these broader roles of IscR in different cellular processes and, in particular, discuss the importance of IscR as a virulence factor for many bacterial pathogens., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
- Published
- 2024
- Full Text
- View/download PDF
42. Pesticide butachlor exposure perturbs gut microbial homeostasis.
- Author
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Li A, Liu F, Si W, Wang Y, Wang D, Yuan Z, Li L, Kiani FA, and Jiang X
- Subjects
- Animals, Herbicides toxicity, Pesticides toxicity, Male, Antioxidants metabolism, Environmental Pollutants toxicity, Gastrointestinal Microbiome drug effects, Homeostasis drug effects, Acetanilides toxicity
- Abstract
Agricultural production relies heavily on the use of pesticides, which may accumulate in soil and water, posing a significant threat to the global ecological environment and biological health. Butachlor is a commonly used herbicide and environmental pollutant, which has been linked to liver and kidney damage, as well as neurological abnormalities. However, the potential impact of butachlor exposure on the gut microbiota remains understudied. Thus, our aim was to investigate the potential negative effects of butachlor exposure on host health and gut microbiota. Our results demonstrated that butachlor exposure significantly reduced the host antioxidant capacity, as evidenced by decreased levels of T-AOC, SOD, and GSH-Px, and increased levels of MDA. Serum biochemical analysis also revealed a significant increase in AST and ALT levels during butachlor exposure. Microbial analysis showed that butachlor exposure significantly reduced the abundance and diversity of gut microbiota. Furthermore, butachlor exposure also significantly altered the gut microbial composition. In conclusion, our findings indicate that butachlor exposure can have detrimental health effects, including dysregulation of antioxidant enzymes, abnormalities in transaminases, and hepatointestinal damage. Furthermore, it disrupts the gut microbial homeostasis by altering microbial composition and reducing diversity and abundance. In the context of the increasingly serious use of pesticides, this study will help provide impetus for standardizing the application of pesticides and reducing environmental pollution., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
43. SNP alleviates mitochondrial homeostasis dysregulation-mediated developmental toxicity in diabetic zebrafish larvae.
- Author
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Jiang Y, Cao Y, Li Y, Bi L, Wang L, Chen Q, Lin Y, Jin H, Xu X, Peng R, and Chen Z
- Subjects
- Animals, Apoptosis drug effects, Oxidative Stress drug effects, Reactive Oxygen Species metabolism, Signal Transduction drug effects, Glucose metabolism, Glucose toxicity, Nitric Oxide metabolism, Lipid Peroxidation drug effects, Ferroptosis drug effects, Zebrafish, Mitochondria metabolism, Mitochondria drug effects, Mitochondria pathology, Homeostasis drug effects, Larva drug effects
- Abstract
The incidence of diabetes is increasing annually, and the disease is uncurable due to its complex pathogenesis. Therefore, understanding diabetes pathogenesis and developing new treatments are crucial. This study showed that the NO donor SNP (8 µM) significantly alleviated high glucose-induced developmental toxicity in zebrafish larvae. High glucose levels caused hyperglycemia, leading to oxidative stress and mitochondrial damage from excessive ROS accumulation. This promoted mitochondrial-dependent apoptosis and lipid peroxidation (LPO)-induced ferroptosis, along with immune inflammatory reactions that decreased mitochondrial function and altered intracellular grid morphology, causing imbalanced kinetics and autophagy. After SNP treatment, zebrafish larvae showed improved developmental toxicity and glucose utilization, reduced ROS accumulation, and increased antioxidant activity. The NO-sGC-cGMP signaling pathway, inhibited by high glucose, was significantly activated by SNP, improving mitochondrial homeostasis, increasing mitochondrial count, and enhancing mitochondrial function. It's worth noting that apoptosis, ferroptosis and immune inflammation were effectively alleviated. In summary, SNP improved high glucose-induced developmental toxicity by activating the NO-sGC-cGMP signaling pathway to reduce toxic effects such as apoptosis, ferroptosis and inflammation resulting from mitochondrial homeostasis imbalance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
44. Hydrogen sulfide maintains mitochondrial homeostasis and regulates ganoderic acids biosynthesis by SQR under heat stress in Ganoderma lucidum.
- Author
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Shangguan J, Wu T, Tian L, Liu Y, Zhu L, Liu R, Zhu J, Shi L, Zhao M, and Ren A
- Subjects
- Quinone Reductases metabolism, Quinone Reductases genetics, DNA, Mitochondrial genetics, Electron Transport Complex III metabolism, Electron Transport Complex III genetics, Hydrogen Sulfide metabolism, Reishi metabolism, Reishi genetics, Triterpenes metabolism, Mitochondria metabolism, Homeostasis, Heat-Shock Response, Membrane Potential, Mitochondrial drug effects
- Abstract
Hydrogen sulfide (H
2 S) has recently been recognized as an important gaseous transmitter with multiple physiological effects in various species. Previous studies have shown that H2 S alleviated heat-induced ganoderic acids (GAs) biosynthesis, an important quality index of Ganoderma lucidum. However, a comprehensive understanding of the physiological effects and molecular mechanisms of H2 S in G. lucidum remains unexplored. In this study, we found that heat treatment reduced the mitochondrial membrane potential (MMP) and mitochondrial DNA copy number (mtDNAcn) in G. lucidum. Increasing the intracellular H2 S concentration through pharmacological and genetic means increased the MMP level, mtDNAcn, oxygen consumption rate level and ATP content under heat treatment, suggesting a role for H2 S in mitigating heat-caused mitochondrial damage in G. lucidum. Further results indicated that H2 S activates sulfide-quinone oxidoreductase (SQR) and complex III (Com III), thereby maintaining mitochondrial homeostasis under heat stress in G. lucidum. Moreover, SQR also mediated the negative regulation of H2 S to GAs biosynthesis under heat stress. Furthermore, SQR might be persulfidated under heat stress in G. lucidum. Thus, our study reveals a novel physiological function and molecular mechanism of H2 S signalling under heat stress in G. lucidum with broad implications for research on the environmental response of microorganisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)- Published
- 2024
- Full Text
- View/download PDF
45. Therapeutic targeting of the USP2-E2F4 axis inhibits autophagic machinery essential for zinc homeostasis in cancer progression
- Author
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Wenjing Xiao, Jianqun Wang, Xiaojing Wang, Shuang Cai, Yanhua Guo, Lin Ye, Dan Li, Anpei Hu, Shikai Jin, Boling Yuan, Yi Zhou, Qilan Li, Qiangsong Tong, and Liduan Zheng
- Subjects
Carcinogenesis ,Cell Biology ,E2F Transcription Factors ,Ubiquitin-Specific Peptidase 7 ,Zinc ,Ki-67 Antigen ,Adenosine Triphosphate ,Stomach Neoplasms ,Autophagy ,Humans ,Homeostasis ,Metallothionein ,Ubiquitin-Specific Proteases ,Ubiquitin Thiolesterase ,Molecular Biology ,Research Paper - Abstract
Macroautophagy/autophagy is a conserved cellular process associated with tumorigenesis and aggressiveness, while mechanisms regulating expression of autophagic machinery genes in cancers still remain elusive. Herein, we identified E2F4 (E2F transcription factor 4) as a novel transcriptional activator of cytoprotective autophagy crucial for zinc homeostasis in cancer cells. Gain- and loss-of-function studies showed that E2F4 promoted autophagy in a cell cycle-dependent manner, resulting in facilitated degradation of MT (metallothionein) proteins, elevated distribution of Zn2+ within autophagosomes, decreased labile intracellular zinc ions, and increased growth, invasion, and metastasis of gastric cancer cells. Mechanistically, E2F4 directly regulated the transcription of ATG2A (autophagy related 2A) and ULK2 (unc-51 like autophagy activating kinase 2), leading to autophagic degradation of MT1E, MT1M, and MT1X, while USP2 (ubiquitin specific peptidase 2) stabilized E2F4 protein to induce its transactivation via physical interaction and deubiquitination in cancer cells. Rescue experiments revealed that USP2 harbored oncogenic properties via E2F4-facilitated autophagy and zinc homeostasis. Emetine, a small chemical inhibitor of autophagy, was able to block interaction between UPS2 and E2F4, increase labile intracellular zinc ions, and suppress tumorigenesis and aggressiveness. In clinical gastric cancer specimens, both USP2 and E2F4 were upregulated and associated with poor outcome of patients. These findings indicate that therapeutic targeting of the USP2-E2F4 axis inhibits autophagic machinery essential for zinc homeostasis in cancer progression. Abbreviations: 3-MA: 3-methyladenine; ANOVA: analysis of variance; ATG2A: autophagy related 2A; ATG5: autophagy related 5; ATP: adenosine triphosphate; BECN1: beclin 1; BiFC: bimolecular fluorescence complementation; CCND1: cyclin D1; CDK: cyclin dependent kinase; ChIP: chromatin immunoprecipitation; CHX: cycloheximide; Co-IP: co-immunoprecipitation; DAPI: 4’,6-diamidino-2-phenylindole; E2F4: E2F transcription factor 4; eATP: extracellular adenosine triphosphate; EBSS: Earle’s balanced salt solution; FP: first progression; FRET: fluorescence resonance energy transfer; FUCCI: fluorescent ubiquitination-based cell cycle indicator; GFP: green fluorescent protein; GST: glutathione S-transferase; HA: hemagglutinin; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MDM2: MDM2 proto-oncogene; MKI67/Ki-67: marker of proliferation Ki-67; MT: metallothionein; MT1E: metallothionein 1E; MT1M: metallothionein 1M; MT1X: metallothionein 1X; MTT: 3-(4,5-dimethyltriazol-2-yl)-2,5-diphenyl tetrazolium bromide; OS: overall survival; PECAM1/CD31: platelet and endothelial cell adhesion molecule 1; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; qPCR: quantitative PCR; RFP: red fluorescent protein; SQSTM1/p62: sequestosome 1; UBXN1: UBX domain protein 1; Ub: ubiquitin; ULK2: unc-51 like autophagy activating kinase 2; USP14: ubiquitin specific peptidase 14; USP2: ubiquitin specific peptidase 2; USP5: ubiquitin specific peptidase 5; USP7: ubiquitin specific peptidase 7; ZnCl2: zinc chloride.
- Published
- 2022
46. Journal of Clinical Monitoring and Computing 2019 end of year summary: monitoring tissue oxygenation and perfusion and its autoregulation
- Author
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Thomas Scheeren, Jaap Jan Vos, and Marko M. Sahinovic
- Subjects
medicine.medical_specialty ,Monitoring ,Hemodynamics ,Health Informatics ,PRESSURE ,Critical Care and Intensive Care Medicine ,Cerebral autoregulation ,03 medical and health sciences ,Sevoflurane ,0302 clinical medicine ,Somatic tissue oxygenation ,Oxygen Consumption ,030202 anesthesiology ,TRANSCRANIAL DOPPLER ,Internal medicine ,medicine ,MANAGEMENT ,Animals ,Homeostasis ,Humans ,Autoregulation ,Oximetry ,Cerebral perfusion pressure ,Review Paper ,Spectroscopy, Near-Infrared ,business.industry ,Cerebral tissue oxygenation ,Brain ,Ultrasonography, Doppler ,Cerebral blood flow ,Subarachnoid Hemorrhage ,Transcranial Doppler ,Oxygen ,Perfusion ,Anesthesiology and Pain Medicine ,Tissue oxygenation ,NIRS ,Brain Injuries ,Cerebrovascular Circulation ,Cardiology ,business ,POSTOPERATIVE NAUSEA ,030217 neurology & neurosurgery ,Blood Flow Velocity - Abstract
Tissue perfusion monitoring is increasingly being employed clinically in a non-invasive fashion. In this end-of-year summary of the Journal of Clinical Monitoring and Computing, we take a closer look at the papers published recently on this subject in the journal. Most of these papers focus on monitoring cerebral perfusion (and associated hemodynamics), using either transcranial doppler measurements or near-infrared spectroscopy. Given the importance of cerebral autoregulation in the analyses performed in most of the studies discussed here, this end-of-year summary also includes a short description of cerebral hemodynamic physiology and its autoregulation. Finally, we review articles on somatic tissue oxygenation and its possible association with outcome.
- Published
- 2020
47. Dietary curcumin restores insulin homeostasis in diet-induced obese aged mice
- Author
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Su-Jeong Lee, Prabha Chandrasekran, Caio Henrique Mazucanti, Jennifer F. O’Connell, Josephine M. Egan, and Yoo Kim
- Subjects
Male ,Aging ,Curcumin ,insulin-degrading enzyme (IDE) ,Dietary Sugars ,Cell Biology ,Diet, High-Fat ,Mice ,Random Allocation ,Gene Expression Regulation ,Body Composition ,Animals ,Homeostasis ,Insulin ,type 2 diabetes ,Obesity ,insulin homeostasis ,Research Paper - Abstract
Although aging is a physiological process to which all organisms are subject, the presence of obesity and type 2 diabetes accelerates biological aging. Recent studies have demonstrated the causal relationships between dietary interventions suppressing obesity and type 2 diabetes and delaying the onset of age-related endocrine changes. Curcumin, a natural antioxidant, has putative therapeutic properties such as improving insulin sensitivity in obese mice. However, how curcumin contributes to maintaining insulin homeostasis in aged organisms largely remains unclear. Thus, the objective of this study is to examine the pleiotropic effect of dietary curcumin on insulin homeostasis in a diet-induced obese (DIO) aged mouse model. Aged (18-20 months old) male mice given a high-fat high-sugar diet supplemented with 0.4% (w/w) curcumin (equivalent to 2 g/day for a 60 kg adult) displayed a different metabolic phenotype compared to mice given a high-fat high-sugar diet alone. Furthermore, curcumin supplementation altered hepatic gene expression profiling, especially insulin signaling and senescence pathways. We then mechanistically investigated how curcumin functions to fine-tune insulin sensitivity. We found that curcumin supplementation increased hepatic insulin-degrading enzyme (IDE) expression levels and preserved islet integrity, both outcomes that are beneficial to preserving good health with age. Our findings suggest that the multifaceted therapeutic potential of curcumin can be used as a protective agent for age-induced metabolic diseases.
- Published
- 2022
48. HDAC6 inhibition reverses long-term doxorubicin-induced cognitive dysfunction by restoring microglia homeostasis and synaptic integrity
- Author
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Blake R McAlpin, Rajasekaran Mahalingam, Anand K Singh, Shruti Dharmaraj, Taylor T Chrisikos, Nabila Boukelmoune, Annemieke Kavelaars, and Cobi J Heijnen
- Subjects
Dose-Response Relationship, Drug ,Transcription, Genetic ,HDAC6 inhibition ,Medicine (miscellaneous) ,microglia ,chemobrain ,Histone Deacetylase 6 ,Hippocampus ,chemotherapy-induced cognitive dysfunction ,Mitochondria ,Mice, Inbred C57BL ,Pyridazines ,single-nucleus RNA sequencing ,Mice ,Doxorubicin ,Synapses ,Animals ,Homeostasis ,Cognitive Dysfunction ,Female ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Disks Large Homolog 4 Protein ,Research Paper - Abstract
Breast cancer is the most common female malignancy in both the developed and developing world. Doxorubicin is one of the most commonly used chemotherapies for breast cancer. Unfortunately, up to 60% of survivors report long-term chemotherapy-induced cognitive dysfunction (CICD) characterized by deficits in working memory, processing speed and executive function. Currently, no therapeutic standard for treating CICD exists. Here, we hypothesized that treatment with a blood-brain barrier permeable histone deacetylase 6 (HDAC6) inhibitor can successfully reverse long-term doxorubicin-induced cognitive dysfunction. Methods: The puzzle box test and novel object/place recognition test were used to assess cognitive function following a therapeutic doxorubicin dosing schedule in female mice. Mitochondrial function and morphology in neuronal synaptosomes were evaluated using the Seahorse XF24 extracellular flux analyzer and transmission electron microscopy, respectively. Hippocampal postsynaptic integrity was evaluated using immunofluorescence. Hippocampal microglia phenotype was determined using advanced imaging techniques and single-nucleus RNA sequencing. Results: A 14-day treatment with a blood-brain barrier permeable HDAC6 inhibitor successfully reversed long-term CICD in the domains of executive function, working and spatial memory. No significant changes in mitochondrial function or morphology in neuronal synaptosomes were detected. Long-term CICD was associated with a decreased expression of postsynaptic PSD95 in the hippocampus. These changes were associated with decreased microglial ramification and alterations in the microglia transcriptome that suggest a stage 1 disease-associated microglia (DAM) phenotype. HDAC6 inhibition completely reversed these doxorubicin-induced alterations, indicating a restoration of microglial homeostasis. Conclusion: Our results show that decreased postsynaptic integrity and a neurodegenerative microglia phenotype closely resembling stage 1 DAM microglia contribute to long-term CICD. Moreover, HDAC6 inhibition shows promise as an efficacious pharmaceutical intervention to alleviate CICD and improve quality of life of breast cancer survivors.
- Published
- 2022
49. Pancreatic ductal deletion of S100A9 alleviates acute pancreatitis by targeting VNN1-mediated ROS release to inhibit NLRP3 activation
- Author
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Shilin Xia, Qi Zhou, Dong Shang, Fangyue Guo, Xufeng Tao, Hong Xiang, Lunxu Li, and Dawei Deng
- Subjects
Male ,acinar cells ,acute pancreatitis ,Medicine (miscellaneous) ,GPI-Linked Proteins ,S100A9 ,Amidohydrolases ,Cell Line ,Small Molecule Libraries ,Mice ,Downregulation and upregulation ,In vivo ,NLR Family, Pyrin Domain-Containing 3 Protein ,medicine ,Animals ,Calgranulin B ,Humans ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,VNN1 ,Pancreatic duct ,Inflammation ,Mice, Knockout ,Chemistry ,Pancreatic Ducts ,duct cells ,medicine.disease ,In vitro ,Mice, Inbred C57BL ,Molecular Docking Simulation ,medicine.anatomical_structure ,Pancreatitis ,Cancer research ,Acute pancreatitis ,Reactive Oxygen Species ,Homeostasis ,Research Paper - Abstract
Recent studies have proven that the overall pathophysiology of pancreatitis involves not only the pancreatic acinar cells but also duct cells, however, pancreatic duct contribution in acinar cells homeostasis is poorly known and the molecular mechanisms leading to acinar insult and acute pancreatitis (AP) are unclear. Our previous work also showed that S100A9 protein level was notably increased in AP rat pancreas through iTRAQ-based quantitative proteomic analysis. Therefore, we investigated the actions of injured duct cells on acinar cells and the S100A9-related effects and mechanisms underlying AP pathology in the present paper. Methods: In this study, we constructed S100A9 knockout (s100a9-/-) mice and an in vitro coculture system for pancreatic duct cells and acinar cells. Moreover, a variety of small molecular inhibitors of S100A9 were screened from ChemDiv through molecular docking and virtual screening methods. Results: We found that the upregulation of S100A9 induces cell injury and inflammatory response via NLRP3 activation by targeting VNN1-mediated ROS release; and loss of S100A9 decreases AP injury in vitro and in vivo. Moreover, molecular docking and mutant plasmid experiments proved that S100A9 has a direct interaction with VNN1 through the salt bridges formation of Lys57 and Glu92 residues in S100A9 protein. We further found that compounds C42H60N4O6 and C28H29F3N4O5S can significantly improve AP injury in vitro and in vivo through inhibiting S100A9-VNN1 interaction. Conclusions: Our study showed the important regulatory effect of S100A9 on pancreatic duct injury during AP and revealed that inhibition of the S100A9-VNN1 interaction may be a key therapeutic target for this disease.
- Published
- 2021
50. Chaos in Physiological Control Systems: Health or Disease?
- Author
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Boubaker, Olfa
- Subjects
CANCER cell growth ,CELL populations ,IMAGE encryption - Abstract
During the nineties, the Rössler's have reported in their famous book "Chaos in Physiology," that "physiology is the mother of Chaos." Moreover, several researchers have proved that Chaos is a generic characteristic of systems in physiology. In the context of disease, like for example growth of cancer cell populations, Chaos often refers to irregular and unpredictable patterns. In such cases, Chaos signatures can be used to prove the existence of some pathologies. However, for other physiological behaviors, Chaos is a form of order disguised as disorder and can be a signature of healthy physiological functions. This is for example the case of human brain behavior. As the boundary between health and disease is not always clear-cut in chaotic systems in physiology, some conditions may involve transitions between ordered and chaotic states. Understanding these transitions and identifying critical points can be crucial for predicting Healthy vs. pathological Chaos. Using recent advances in physiological Chaos and disease dynamics, this survey paper tries to answer the crucial question: when Chaos be a sign of health or disease?. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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