Chronic vagotomy induces nTS glial activation, reduced glutamatergic signaling, and blunted cardiorespiratory responses DOI Open Access
Gabrielle C. Hofmann

Published: Jan. 1, 2023

The brainstem nucleus tractus solitarii (nTS) is the first site of integration viscerosensory information provided by afferents vagus nerves. nTS critically contributes to cardiorespiratory function and displays remarkable neuroplasticity in response changes afferent input. Vagal form synapses with neurons that are closely associated astrocytes, forming tripartite synapse. We hypothesized reducing vagal input via chronic unilateral vagotomy would alter synapse nTS, resulting activity. In results Aim 1, we showed induced astrocyte reactivity microglial activation nTS. This corresponded a reduction augmented breaths (sighs) during hypoxia. 2, further investigated effects stimulating recording sympathetic responses. Blunted responses stimulation lead us hypothesize reactive astrocytes at may be contributing this through increased glutamate uptake. Instead found evidence reduced excitability vagotomized decreased postsynaptic NMDA receptor function, leading blunted neuronal upon stimulation. Together these demonstrate multiple occur following vagotomy, contribute reflex affect health disease.

Language: Английский

Hypoxia-Responsive Host–Guest Drug Delivery System DOI
Xin‐Yue Hu, Rong Fu, Dong‐Sheng Guo

et al.

Accounts of Materials Research, Journal Year: 2023, Volume and Issue: 4(11), P. 925 - 938

Published: Oct. 9, 2023

ConspectusA host–guest drug delivery system (HGDDS) refers to a complex of an artificial receptor and therapeutic agent which can dissociate at the lesion site release loaded cargo. Macrocyclic receptors are promising carriers because their superior properties, including ease preparation, precise molecular weight, well-defined structure, excellent chemical stability. The loading process is mild, simple, repeatable. formulations quantitatively load exact cavity-loading pattern quantifiable binding constant. Host–guest typically modular, may be appealing in context personalized medicine macrocyclic act as platform diverse drugs. These lead good batch reproductivity application prospects both scientific research industry. However, order make HGDDS more suitable for practical application, several demands such high affinity, universal multiple drugs, targeting, stimuli-responsiveness still need considered.The hypoxia linked diseases biological processes, cancer, acute chronic diseases, pathogenic microbe infection, other stress responses. As part our ongoing on supramolecular biomaterials based macrocycles by taking advantage recognition assembly we have developed hypoxia-responsive azocalixarenes. azocalixarenes possess deepened cavity, resulting affinities encapsulation efficiencies toward agents. azo group one most frequently employed moieties it reduced under hypoxic microenvironments. This property confers with hypoxia-triggered due remarkable decrease following reduction. fast kinetics further facilitates efficient accumulation drugs site. azocalixarene-based HGDDSs been applied preclinical studies diagnosis treatment tumor, bacterial kidney injury, rheumatoid arthritis.In this Account, outline recent efforts designing formulating We first provide brief introduction HGDDSs, features, quantitative ratiometric models. Then design principles synthesis methods, strong loading, hypoxia-response described. applications treating different followed. Finally, despite rapid development there problems that solved scientifically terms clinical translation. Therefore, propose perspectives conducted HGDDSs.

Language: Английский

Citations

26
Hypoxia-mediated SUMOylation of FADD exacerbates endothelial cell injury via the RIPK1-RIPK3-MLKL signaling axis DOI Creative Commons
Liming Yang,

Yilin Wen,

Zhiyi Yuan

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 21, 2025

Language: Английский

Citations

0
Intermittent hypoxic stimulation promotes efficient expression of Hypoxia-inducible factor-1α and exerts a chondroprotective effect in an animal osteoarthritis model DOI Creative Commons

Ryota Cha,

Shuji Nakagawa, Yuji Arai

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(4), P. e0319976 - e0319976

Published: April 1, 2025

Hypoxia-inducible factor-1α plays an important role in the homeostasis of articular cartilage hypoxic environments. Therefore, modulation hypoxia-inducible by regulating oxygen environment could be a useful treatment for osteoarthritis. This study aimed to assess chondroprotective effects intermittent hypoxia on cultured chondrocytes and animal model In vitro , human were exposed 2 h stimulation three times at 1-h intervals, protein gene expression factor-1α, ACAN, cell viability was measured over time. vivo 8-week-old male Wistar rats injected with monosodium iodoacetate induce osteoarthritis then reared 12% 24 h, followed steady oxygen, repeated alternately total 28 days. A histological analysis performed days 8 28. group, each increased chondrocytes; finally, level significantly higher than continuous stimulation, increased, not increased. model, days, there stronger staining no significant differences destruction. Furthermore, less destruction rat rearing. Intermittent metabolism increasing proteins chondrocytes, which may effective preventing degeneration model.

Language: Английский

Citations

0
Circadian Rhythm, Hypoxia, and Cellular Senescence: From Molecular Mechanisms to Targeted Strategies DOI

Tong Nie,

Eugenie Nepovimová, Qinghua Wu

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177290 - 177290

Published: Jan. 1, 2025

Language: Английский

Citations

0
Innovative in vivo rat model for global cerebral hypoxia: a new approach to investigate therapeutic and preventive drugs DOI Creative Commons

Sarah Stahlke,

Jonas Frai,

J. Busse

et al.

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 9, 2024

Introduction: Severe acute global cerebral hypoxia can lead to significant disability in humans. Although different animal models have been described study hypoxia, there is no endogenous model that considers and its effect on the brain as an independent factor. Thus, we developed a minimally invasive rat model, which based non-depolarizing muscle blocking agent rocuronium anesthetized animals. This drug causes respiratory insufficiency by paralysis of striated muscles. Methods: In this study, 14 rats underwent 12 min hypoxemia with oxygen saturation approximately 60% measured pulse oximetry; thereafter, animals obtained sugammadex antagonize immediately. Results: Compared controls (14 rats, anesthesia only), hypoxic demonstrated morphological alterations hippocampus (cell decrease CA 1 region) cerebellum (Purkinje cell decrease), well changes markers blood (Hif2α, Il1β, Tgf1β, Tnfα, S100b, cspg2, neuron-specific enolase), (Il1β, NSE), (Hif1α, NSE). Effects were more pronounced females than males. Discussion: Consequently, suitable induce consecutive hypoxia. As biochemical proven, it be used investigate therapeutic preventive drugs for

Language: Английский

Citations

1
Salidroside rescues hypoxic cardiomyocytes by regulating the EGLN1/HIF‑1α pathway DOI Open Access

Wenmao Zhang,

Ziling Liao,

Chengfeng Xu

et al.

Biomedical Reports, Journal Year: 2024, Volume and Issue: 21(6)

Published: Oct. 2, 2024

Myocardial infarction is characterized by oxygen deficiency caused arterial flow restriction. Salidroside (SAL) protects against myocardial damage via antioxidant production and inhibition of apoptosis. The present study aimed to investigate potential rescue mechanism SAL on hypoxic cardiomyocytes. H9C2 cardiomyocytes were divided into normoxia, hypoxia + groups. inhibitory rate the optimal concentration effect determined using Cell Counting Kit-8 assay cytometry. Ca

Language: Английский

Citations

0
Influence of Hypoxia on the Airway Epithelium DOI Creative Commons

K Procházková,

Jir̆ı́ Uhlı́k

Physiological Research, Journal Year: 2024, Volume and Issue: unknown, P. S557 - S568

Published: Nov. 25, 2024

The necessity of oxygen for metabolic processes means that hypoxia can lead to serious cell and tissue damage. On the other hand, in some situations, occurs under physiological conditions serves as an important regulation factor. airway epithelium is specific it gains not only from blood supply but also directly luminal air. Many respiratory diseases are associated with obstruction or excessive mucus production thus leading hypoxia. main goal this review point out how reacts hypoxic conditions. Cells detect low levels using molecular mechanisms involving hypoxia-inducible factors (HIFs). In addition, cells appear overexpress HIFs then regulate many aspects epithelial functions. effects include secretory stimulation hyperplasia, barrier changes, ciliogenesis impairment. All changes impair mucociliary clearance, exacerbate infection, promote inflammation damage subsequent wall remodeling. modulation regulatory may be one strategies treatment obstructive hyperproduction. Keywords: Secretory cells, Motile cilia, Epithelial barrier, Oxygenation, Obstructive diseases.

Language: Английский

Citations

0
Impact of Hypoxia on Alveolar Bone Dynamics and Remodeling DOI Creative Commons
Sangeetha Narasimhan, Sausan Al Kawas, Shishir Shetty

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(23), P. e40868 - e40868

Published: Dec. 1, 2024

Oxygen is a fundamental requirement for cellular metabolism. Hypoxia state of oxygen deprivation the tissues. Cells develop numerous adaptive mechanisms to survive hypoxic insult. Alveolar bone unique structure that encases and protects tooth. Literature reports hypoxia, in all forms, impacts alveolar health. The hypoxia-inducible pathway appears play key role mediating changes Embryonic hypoxia plays vital craniofacial skeletal development. Further, has been anticipated repair extraction sockets. cells respond distinctly conditions with both beneficial detrimental effects. Studies have demonstrated enhanced resorption upon stimuli. However, also shown potential therapeutic effects on by triggering an angiogenic response. Additionally, type, duration, mode are critical varied responses main objective this review recapitulate different types tooth supporting apparatus analyze some presumptive underlying hypoxia-induced remodeling.

Language: Английский

Citations

0
СКРИНІНГОВІ ДОСЛІДЖЕННЯ АНТИГІПОКСИЧНИХ ВЛАСТИВОСТЕЙ ФАРМАЦЕВТИЧНОЇ КОМПОЗИЦІЇ НА ОСНОВІ ЛІВОКАРНІТИНУ ДЛЯ КОРЕКЦІЇ НАСЛІДКІВ ФЕТОПЛАЦЕНТАРНОЇ НЕДОСТАТНОСТІ DOI Open Access
І. V. Volokhov,

В. А. Рыбак,

L. Yu. Sergienko

et al.

Фармацевтичний часопис, Journal Year: 2023, Volume and Issue: 1, P. 50 - 57

Published: March 30, 2023

Мета роботи: становити антигіпоксичні властивості фармацевтичної композиції на основі лівокарнітину. Матеріали та методи. Дослідження антигіпоксичних властивостей лівокарнітину проведено двох експериментальних моделях гострої гіпоксії, відтворених нелінійних мишах-самцях (Mus musculus). Щоденно впродовж 15 діб за годину до проведення тестів із визначення антигіпоксичної дії тваринам вводили ФК лівокарнітину, а мишам групи позитивного контролю – референтний препарат мексикор. Ефективність гіпоксії визначено показниками: коефіцієнт активності, середня тривалість життя тварин відносна антигіпоксична активність. Результати й обговорення. Встановлено, що фармацевтична композиція в дозі 25 мг/кг моделі нормобаричної з гіперкапнією проявляє найбільшу антигіпоксичну активність, яка становить 31 %, відповідає активності препарату порівняння мексикор у 16 мг/кг. На гемічної більш виражену активність мг/кг, 41 % є дещо вищою порівняно мексикором мг/кг. Висновки. Визначено, при внутрішньошлунковому введенні найбільш дію референс-препаратом (41 проти 33 %). Профілактичне введення підвищує стійкість гіпоксичних станів. Встановлено зумовлює перспективність подальших фармакологічних досліджень для застосування медичній практиці метою профілактики наслідків фетоплацентарної недостатності.

Citations

0
Chronic vagotomy induces nTS glial activation, reduced glutamatergic signaling, and blunted cardiorespiratory responses DOI Open Access
Gabrielle C. Hofmann

Published: Jan. 1, 2023

The brainstem nucleus tractus solitarii (nTS) is the first site of integration viscerosensory information provided by afferents vagus nerves. nTS critically contributes to cardiorespiratory function and displays remarkable neuroplasticity in response changes afferent input. Vagal form synapses with neurons that are closely associated astrocytes, forming tripartite synapse. We hypothesized reducing vagal input via chronic unilateral vagotomy would alter synapse nTS, resulting activity. In results Aim 1, we showed induced astrocyte reactivity microglial activation nTS. This corresponded a reduction augmented breaths (sighs) during hypoxia. 2, further investigated effects stimulating recording sympathetic responses. Blunted responses stimulation lead us hypothesize reactive astrocytes at may be contributing this through increased glutamate uptake. Instead found evidence reduced excitability vagotomized decreased postsynaptic NMDA receptor function, leading blunted neuronal upon stimulation. Together these demonstrate multiple occur following vagotomy, contribute reflex affect health disease.

Language: Английский

Citations

0