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Preprint REVIEW | doi:10.20944/preprints202305.1766.v1

Hypoxic-Ischemic Brain Injury in ECMO: Pathophysiology, Neuromonitoring, and Therapeutic Opportunities

Shivalika Khanduja, Jiah Kim, Jin Kook Kang, Cheng-Yuan Feng, Melissa Ann Vogelsong, Romergryko G Geocadin, Glenn Whitman, Sung-Min Cho

Subject: Medicine And Pharmacology, Clinical Medicine Keywords: hypoxia-ischemia brain injury; extracorporeal membrane oxygenation; neurological complication; neu-romonitoring; outcome.

Online: 25 May 2023 (08:26:02 CEST)

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Preprint REVIEW | doi:10.20944/preprints202103.0770.v1

Role of Citicoline in the Management of Traumatic Brain Injury

Julio J Secades

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: CDP-choline; citicoline; pharmacological neuroprotection; brain ischemia; traumatic brain injury; head injury

Online: 31 March 2021 (14:42:27 CEST)

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Working Paper REVIEW

HypoxiaInducible Factor (HIF) in Ischemic Stroke and Neurodegenerative Disease

Elena Mitroshina, Maria Savyuk, Evgeni Ponimaskin, Maria Vedunova

Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Hypoxia Inducible Factor; HIF; Ischemia; Hypoxia; Adaptation; Alzheimer’s Disease; Parkinson Disease; Neurodegeneration

Online: 26 February 2021 (15:34:31 CET)

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Preprint ARTICLE | doi:10.20944/preprints202305.0386.v1

The Power of Nutraceuticals Fighting Liver Ischemia–Reperfusion Injury Through Apoptosis Reduction

Carlos Andrés Pantanali, Vinicius Rocha-Santos, Márcia Saldanha Kubrusly, Inar Alves Castro, Luiz Augusto Carneiro-D’Albuquerque, Flávio Henrique Galvão

Subject: Medicine And Pharmacology, Transplantation Keywords: nutraceuticals; liver; ischemia-reperfusion injury; apoptosis

Online: 6 May 2023 (05:46:56 CEST)

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Working Paper REVIEW

Therapeutic Effect of Mesenchymal Stem Cell on Organ Ischemia-Reperfusion Injury

Joan Oliva

Subject: Medicine And Pharmacology, Transplantation Keywords: ischemia-reperfusion injury; mesenchymal stem cells; treatment

Online: 11 June 2019 (04:28:04 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202012.0082.v1

Cytochrome P450 CYP2E1 Suppression Ameliorates Cerebral Ischemia Reperfusion Injury

Jin Yu, Hong Zhu, Mark Kindy, Saeid Taheri

Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Oxidative stress; CYP2E1; Ischemia/reperfusion; Inflammation; Blood-brain barrier

Online: 3 December 2020 (11:05:57 CET)

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Preprint REVIEW | doi:10.20944/preprints202203.0301.v1

Acute Heart Failure, 90-day Mortality—and Gravitational Ischemia in the Brain

J. Howard Jaster, Giulia Ottaviani

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Heart Failure; Gravity; Ischemia; Brain

Online: 22 March 2022 (12:38:29 CET)

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During the 90 days following hospitalization for acute heart failure, ejection fraction and type of discharge medications have been shown in clinical trials to have little effect on mortality. We examined the recent literature addressing brain-related etiologies of sudden death following heart failure. Two mechanisms of sudden unexpected death have been suggested to possibly result from 4 significant influences on pathophysiology in the brain. The two causes of death are severe cardiac arrhythmia, and neurogenic pulmonary edema. They are both mediated through the brainstem autonomic nuclei generally, and executed specifically through the dorsal motor nucleus of the vagus nerve. The four significant influences on pathophysiology in the brainstem autonomic nuclei are: 1) Hyper-stimulation of neurons in the solitary tract nucleus, increasing their metabolic requirements; 2) Inadequate blood flow at a vascular watershed terminus; 3) Additionally decreased blood flow following vasoconstriction related to relative hyperventilation and decreased pCO2 levels; 4) Gravitational ischemia in the brain—caused by the weight of the brain mass sitting above the brainstem. Changes in head tilt release gravitational ischemia in the brain. There is no specific head position (relative to gravity) that is considered favorable or unfavorable for an extended period of time (i.e. more than 24 hours). Even a small degree of head elevation, used in managing pulmonary congestion, may increase gravitational ischemia in the posterior fossa and brainstem. In this paper we suggest a new and important research avenue for intervening in cardiac arrhythmias, and preventing their occurrence, through the non-invasive use of head-tilting, and other head repositioning maneuvers. This could potentially help many geriatric patients with heart failure, who have decreased mobility in bed, and who tend to stay in one position longer, thereby increasing gravitational ischemia in the brain.

Preprint ARTICLE | doi:10.20944/preprints202403.1456.v1

The Effect of “Proanthocyanidin” on Ischemia-Reperfusion Injury in Skeletal Muscles of Rats

Abdullah Özer, Başak Koçak, Şaban Cem Sezen, Mustafa Arslan, Mustafa Kavutçu

Subject: Medicine And Pharmacology, Surgery Keywords: Ischemia reperfusion; proanthocyanidin; lower extremity; rat; TBARS

Online: 25 March 2024 (08:53:48 CET)

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BACKGROUND: Lower limb skeletal muscle ischemia-reperfusion (IR) injury associated with increased morbidity and mortality is common in several clinical situations such as aortic aneurysms repairment, peripheral arterial surgery, vascular injury repairment, and shock. Although it is generally accepted that oxidative stress mediators have a significant role in IR injury, its precise mechanism is still unknown. Anecdotally, it is sustained not only by structural and functional changes in the organ it affects but also by damage to distant organs. The purpose of this report is to illustrate the effect of proanthocyanidin on IR injury. METHODS: In our study, 18 male Wistar albino rats were used. The subjects were divided into three groups of six each. (Group Control-C, Group Ischemia-Reperfusion -IR, Group Ischemia-Reperfusion and Proanthocyanidin-IR-PRO). Intraperitoneal proanthocyanidin was given to the IR and proanthocyanidin groups 30 minutes before laparotomy and 1-hour ischemia led to these two groups. After one hour, reperfusion started. Muscle atrophy-hypertrophy, muscle degeneration-congestion, fragmentation-hyalinization, muscle oval-central nucleus ratio, leukocyte cell infiltration, catalase enzyme activity, and TBARS were all examined in lower-limb muscle samples after one hour of reperfusion. RESULTS: When skeletal muscle samples were evaluated histopathologically, it was discovered that muscle atrophy-hypertrophy, muscle degeneration-congestion, fragmentation-hyalinization, and leukocyte cell infiltration with oval-central nucleus standardization were significantly higher in the IR group than group control and group IR-proanthocyanidin. Besides, oval-central nucleus standardization was significantly higher in the IR and proanthocyanidin group than in the control group. TBARS levels were significantly higher in the IR group than in the control and IR-proanthocyanidin groups while, catalase enzyme activity was found to be significantly lower in the IR group than in the control and IR and proanthocyanidin groups. CONCLUSION: As a consequence of our research, we discovered that proanthocyanidins administered before IR have a protective impact on skeletal muscle in rats. Further research in this area is required.

Preprint REVIEW | doi:10.20944/preprints201808.0027.v1

The Hedgehog Signaling Pathway in the Ischemic Heart, Brain, and Skeletal Muscle

Igor Giarretta, Eleonora Gaetani, Paolo Tondi, Takayuki Asahara, Roberto Pola

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Hedgehog; Ischemia; Heart; Brain; Skeletal muscle

Online: 1 August 2018 (16:31:01 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202312.1752.v1

Camphene as a Protective Agent in Myocardial Ischemia/ Reperfusion Injury

Rodopi Stamatiou, Maria Anagnostopoulou, Chrysa Rapti, Antigone Lazou

Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: camphene; ischemia/reperfusion injury; oxidative stress; antioxidant activity; redox homeostasis

Online: 22 December 2023 (15:07:08 CET)

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Preprint ARTICLE | doi:10.20944/preprints202302.0276.v1

Hypoxia-Induced Cardiomyocyte Apoptosis Exacerbates Cardiomyocyte Hypertrophy and Myocardial Injury through p38 MAPK Pathway in SD Rats

Xiaoxu Li, Zhijun Pu, Gang Xu, Yidong Yang, Yu Cui, Xiaoying Zhou, Chenyuan Wang, Zhifeng Zhong, Simin Zhou, Jun Yi, Fabo Shan, Chengzhong Yang, Li Jiao, Dewei Chen, Jian Huang

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Hypoxia; p38; Apoptosis; Cardiomyocyte Hypertrophy; Myocardial Injury

Online: 16 February 2023 (07:21:53 CET)

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Preprint ARTICLE | doi:10.20944/preprints202208.0158.v1

Regulation Microglia Activation Mediated Neuroinflammation to Ameliorate Ischemia-reperfusion Injury via STAT5-NF-κB Pathway in Ischemic Stroke

Zhijun Pu, Shengnan Xia, Pengfei Shao, Xinyu Bao, Dan Wu, Yun Xu

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: dauricine; STAT5; NF-κB; Inflammation; Ischemia-reperfusion injury

Online: 8 August 2022 (13:18:00 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201808.0395.v1

Radix Scrophulariae Aqueous Extract Seems to Exert Neuroprotective Effects on Cerebral Ischemia and Reperfusion Injury with Inhibiting Apoptosis via ERK1/2 and p-38 MAPK Pathway

Weijie Xie, Ping Zhou, Xuelian Zhang, Chenyang Zhang, Xiangbao Meng, Guibo Sun, Xiaobo Sun

Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: Radix scrophulariae; ischemia stroke; cerebral ischemia and reperfusion; apoptosis; ERK1/2 MAPK; p-38 MAPK

Online: 22 August 2018 (11:07:43 CEST)

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Preprint REVIEW | doi:10.20944/preprints202306.1277.v1

Phytocompounds from Amazonian Plant Species against Acute Kidney Injury: Potential Nephroprotective Effects

Alberto Souza Paes, Rosemary de Carvalho Rocha Koga, Priscila Faimann Sales, Hellen Karine Santos Almeida, Thiago Afonso Carvalho Celestino Teixeira, José Carlos Tavares Carvalho

Subject: Medicine And Pharmacology, Urology And Nephrology Keywords: Traditional medicine; phytotherapy; hypoxia; oxidative stress; nephroprotection; antioxidant; anti-inflammatory; diuretic.

Online: 19 June 2023 (03:48:42 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202311.1678.v1

Tubular Endogenous Erythropoietin Protects Renal Function against Ischemic Reperfusion Injury

Yukiko Yasuoka, Yuichiro Izumi, Takashi Fukuyama, Tomomi Oshima, Taiga Yamazaki, Takayuki Uematsu, Noritada Kobayashi, Masayoshi Nanami, Yoshitaka Shimada, Yasushi Nagaba, Masashi Mukoyama, Jeff M Sands, Noriko Takahashi, Katsumasa Kawahara, Hiroshi Nonoguchi

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: erythropoietin; PHD inhibitor; hypoxia; deglycosylation; proximal tubules; distal tubules; renal erythropoietin-producing interstitial cells

Online: 27 November 2023 (08:44:10 CET)

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Preprint ARTICLE | doi:10.20944/preprints201708.0015.v1

Omega-3 polyunsaturated fatty acids protect against ischemia-reperfusion renal injury through AMPK-mediated autophagy

Do Hyeong Gwon, Tae Woong Hwang, Ju-ye Ro, Yoon-Joong Kang, Jin Young Jeong, Do-Kyung Kim, Kyu Lim, Dong Woon Kim, Dae Eun Choi, Jwa-Jin Kim

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: ischemia-reperfusion injury (IRI), ω3-PUFA, AMP-activated protein kinase (AMPK), autophagy

Online: 4 August 2017 (12:56:08 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202402.0945.v1

The Effect of Cerium Oxide (CeO2) on Ischemia-Reperfusion Injury in Skeletal Muscle in Mice with Streptozocin-Induced Diabetes

Abdullah Özer, Necmiye Şengel, Ayşegül Küçük, Zeynep Yığman, Çağrı Özdemir, Yiğit Kılıç, Ali Doğan Dursun, Hasan Bostancı, Gülay Kip, Mustafa Arslan

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: diabetes mellitus; cerium oxide; skeletal muscle; lower limb; ischemia-reperfusion

Online: 19 February 2024 (14:12:37 CET)

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Preprint ARTICLE | doi:10.20944/preprints202306.0551.v1

Detection of Brain Tissue Damage in CO Poisoning with a New Method

Sedat Ozbay, Mustafa Ayan, Recep Eroz, Ayhan Saritas

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Argyrophilic Nucleolus Organizer Region; Hypoxia; Brain; Carbon Monoxide Poisoning; Marker

Online: 7 June 2023 (12:11:19 CEST)

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Working Paper ARTICLE

Aerobic Exercise Attenuates Myocardial Ischemia-Reperfusion Injury in Rats by Regulating The SIRT3/SOD2/NF-κB Pathway

cailian ruan, Yan Yang, ZiLin Li

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Aerobic exercise; Myocardial ischemia/reperfusion; autophagy; SIRT3; SOD2; NF-κB; Biochemical indicators

Online: 1 April 2021 (13:28:32 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202001.0110.v1

Gelidium amansii Attenuates Hypoxia/Reoxygenation-Induced Oxidative Injury in Primary Hippocampal Neurons through Suppressing GluN2B Expression

Md. Abdul Hannan, Md. Nazmul Haque, Md. Mohibbullah, Raju Dash, Yong-Ki Hong, Il Soo Moon

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: oxidative stress; reactive oxygen species; hypoxia-reoxygenation; GluN2B; CNS neuron; Gelidium amansii

Online: 11 January 2020 (14:05:37 CET)

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Preprint ARTICLE | doi:10.20944/preprints202304.1055.v1

A Comprehensive Overview of Innovative Approaches to Prevent Kidney Ischemia-Reperfusion Injury: Bibliometric and In Silico Analyses

Myltykbay S. Rysmakhanov, Afshin Zare, Aibolat S. Smagulov, Nurgul A. Abenova, Nadiar M. Mussin, Yerlan B. Sultangereyev, Bazylbek S. Zhakiyev, Gani K. Kuttymuratov, Mehmet Haberal, Nazanin Jafari, Hanieh Baneshi, Shabnam Bakhshalizadeh, Mahdi Mahdipour, Farhad Rahmanifar, Amin Tamadon

Subject: Medicine And Pharmacology, Urology And Nephrology Keywords: Ischemia/reperfusion injury; Molecular docking; Bibliometric analysis; Kidney reperfusion; Kidney transplantation; Renal resection

Online: 27 April 2023 (07:25:20 CEST)

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Ischemia-reperfusion injury (IRI) is a complex pathophysiological process that can lead to severe and irreversible consequences, including the complete loss of renal function. While standardized strategies for preventing IRI during "back-table" and cold preservation are available, various intraoperative prevention methods have been proposed to mitigate the harmful effects of warm ischemia and reperfusion of the kidney. These methods include pharmacological agents, mechanical interventions, and surgical techniques such as renal capsulotomy, ischemic preconditioning, venous blood reperfusion, renal perfusion, and the use of tissue engineering techniques like mesenchymal stromal/stem cells and/or decellularization. In this comprehensive analysis, we provide a detailed overview of pharmacological agents and intraoperative methods and approaches for the prevention and treatment of renal IRI. We begin by discussing the mechanisms of IRI and the challenges of preventing it during surgery. Then using a bibliometric analysis and molecular docking of brand-new legends we showed eplerenone have the most binding affinity to Aldehyde dehydrogenase (AD), Estrogen receptor (ER), Klotho protein, Mineralocorticoid receptor (MR), and Toll-like receptor 4 (TLR4) for preventing IRI comparing with other available therapeutics, Benzodioxole, Hydrocortisone, Indoles, Nicotinamide adenine dinucleotide, and Niacinamide. Next, we provide a comprehensive analysis of the potential benefits and limitations of various prevention strategies, including an in-depth discussion of the mechanisms of action of pharmacological agents, mechanical interventions, and surgical techniques. Furthermore, we introduce a novel scoring system for the prevention methods of kidney IRI, which takes into account the effectiveness, feasibility, and safety of each method. We then analyze the current state of clinical research in this area and discuss the implications of these methods for future clinical practice. Overall, this article provides a valuable resource for clinicians and researchers seeking to prevent and treat renal IRI in surgical settings, and introduces a new scoring system that can be used to guide the selection of the most effective and safe prevention methods.

Preprint ARTICLE | doi:10.20944/preprints202305.0309.v1

NCX 470, a Dual Acting Nitric Oxide (NO)-Donating Bimatoprost Derivative, Preserves Rabbit Eyes from Biochemical and Functional Changes Associated with ET-1-Induced Ischemia/Reperfusion Injury

Silvia Sgambellone, Silvia Marri, Serafina Villano, Emanuela Masini, Gustavo Provensi, Elena Bastia, Corinna Galli, Stefania Brambilla, Francesco Impagnatiello, Laura Lucarini

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: nitric oxide; bimatoprost; ischemia/reperfusion; oxidative stress; inflammation; apoptosis

Online: 5 May 2023 (06:00:47 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202308.0729.v1

GC-MS Based Cerebrospinal Fluid Metabolomics to Reveal the Protection of Coptisine against Transient Focal Cerebral Ischemia-Reperfusion Injury via Antiinflammation and Antioxidant

Jun Jie Zhang, Ao Qi, Lu lu Liu, Chun Cai, Hui Xu

Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: Cerebral ischemia-reperfusion; Coptisine; arachidonic acid metabolomics; inflammation; and oxidative stress

Online: 9 August 2023 (08:00:20 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202105.0067.v1

Modulation of Endocannabinoids by Caloric Restriction is Conserved in Mice but is not Required for the Protection from Acute Kidney Injury

K. Johanna R. Hoyer-Allo, Martin Richard Späth, Ruth Hanssen, Marc Johnsen, Susanne Brodesser, Kathrin Kaufmann, Katharina Kiefer, Felix C. Koehler, Heike Göbel, Torsten Kubacki, Franziska Grundmann, Bernhard Schermer, Jens Brüning, Thomas Benzing, Volker Burst, Roman-Ulrich Müller

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: acute kidney injury; ischemia-reperfusion injury; dietary restriction; nutrition; preconditioning; endocannabinoids; AEA

Online: 5 May 2021 (13:59:13 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202206.0214.v1

Theory and Applications of the (Cardio) Genomic Fabric Approach to Post-Ischemic and Hypoxia-Induced Heart Failure

Dumitru Andrei Andrei Iacobas, Lei Xi

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Adra1b; cardiac ischemia; hypoxia; Crem; gene expression control; gene expression coordination; gene hierarchy; heart failure; transcriptomic stoichiometry

Online: 15 June 2022 (07:37:53 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201812.0128.v1

Novel Role of MCP-Induced Protein 1 in Ischemic Brain Damage in Animals of Transient Focal Ischemia

Zhuqing Jin, Jian Liang, Jiaqi Li, Pappachan E. Kolattukudy

Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: middle cerebral artery occlusion (MCAO); MCPIP1; blood-brain barrier; inflammatory response; ischemia; metalloproteinases

Online: 11 December 2018 (10:49:54 CET)

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Preprint ARTICLE | doi:10.20944/preprints202401.1506.v1

Hypoxia-Induced Pulmonary Injury—Adrenergic Blockade Attenuates Nitrosative Stress and Inflammation but Not Pulmonary Edema

Isabel Riha, Aida Salameh, Annekathrin Hoschke, Coralie Raffort, Julia Koedel, Beate Rassler

Subject: Medicine And Pharmacology, Anatomy And Physiology Keywords: Normobaric hypoxia; adrenergic blockade; pulmonary edema; pulmonary inflammation; tumor necrosis factor; nitrotyrosine; left and right ventricular catheterization

Online: 19 January 2024 (12:15:30 CET)

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Preprint CASE REPORT | doi:10.20944/preprints202312.0283.v1

Ventilation Management in a Patient with Ventilation-Perfusion Mismatch in the Early Phase of Lung Injury and During the Recovery

Ana Cicvaric, Josipa Glavas Tahtler, Tajana Turk, Sanda Škrinjarić Cincar, Despoina Koulenti, Nenad Neskovic, Mia Edl, Slavica Kvolik

Subject: Medicine And Pharmacology, Anesthesiology And Pain Medicine Keywords: Ventilation, pulmonary; Lung Injury; Personalized ventilation; Hypoxia; Pulmonary Diffusing Capacity; Intensive care; Pneumonia; Stenotrophomonas maltophilia

Online: 5 December 2023 (15:24:52 CET)

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Preprint ARTICLE | doi:10.20944/preprints202307.0428.v1

Fetal oxygenation from the 23rd to the 36th week of gestation evaluated through the umbilical cord blood gas analysis

Luca Filippi, Francesca Pascarella, Alessandro Pini, Maurizio Cammalleri, Paola Bagnoli, Riccardo Morganti, Francesca Innocenti, Nicola Castagnini, Alice Melosi, Rosa Teresa Scaramuzzo

Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: newborn, intrauterine hypoxia, fetal hypoxia, differentiation

Online: 7 July 2023 (07:28:56 CEST)

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Preprint REVIEW | doi:10.20944/preprints202306.0567.v1

Stable Coronary Artery Disease: Who Finally Benefits from Coronary Revascularization in the Modern Era? The ISCHEMIA and Interim ISCHEMIA-EXTEND Analysis

Leonid L Bershtein, Alexey Sumin, Elizaveta Zbyshevskaya, Victoria Gumerova, Darejan Tsurtsumia, Igor Kochanov, Alina Andreeva, Vartan Piltakian, Sergey Sayganov

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: chronic coronary syndromes; revascularization; prognosis; ISCHEMIA; ISCHEMIA-EXTEND

Online: 8 June 2023 (02:13:16 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202112.0158.v1

Transient Receptor Potential Vanilloid Type 1 Contributes to Modulate the Nitric Oxide Pathway and Oxidative Stress in the Isolated and Perfused Rat Heart during Ischemia and Reperfusion

Vicente Castrejón-Téllez, Leonardo Del Valle-Mondragón, Israel Pérez-Torres, Verónica Guarner-Lans, Gustavo Pastelín-Hernández, Angélica Ruíz-Ramírez, Julieta Anabell Díaz-Juárez, Elvira Varela-López, Victor Hugo Oidor-Chan, Alvaro Vargas-González, Raúl Martínez-Memije, Pedro Flores-Chávez, Bruno León-Ruíz, Sergio Arriaga-Carrillo, Juan Carlos Torres-Narváez

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Ischemia reperfusion; TRPV1; cardioprotection

Online: 9 December 2021 (15:38:27 CET)

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Preprint REVIEW | doi:10.20944/preprints202404.0337.v1

The Role of Tnf and Soluble Tnf Receptors (TNFR1/2) as Therapeutic Targets for Inflammation Secondary to Intracerebral Stroke and Hemorrhage

Rakan Alshaibi, Kanishka Ekanayake, Emily Barlow, Ali Ahmed Mohamed, Brandon Lucke-Wold

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: cerebroprotection; ischemia; tumor necrosis factor

Online: 4 April 2024 (06:04:04 CEST)

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Preprint REVIEW | doi:10.20944/preprints202308.1664.v1

Limb Salvage and Survival in Chronic Limb-Threatening Ischemia: The Need for Fast-Track Team-Based Approach

Giorgio Ventoruzzo, Giulia Mazzitelli, Umberto Ruzzi, Francesco Liistro, Alessia Scatena, Eugenio Martelli

Subject: Medicine And Pharmacology, Clinical Medicine Keywords: peripheral arterial disease; critical limb ischemia; chronic limb-threatening ischemia; survival; mortality; limb salvage

Online: 25 August 2023 (02:41:49 CEST)

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Preprint REVIEW | doi:10.20944/preprints202012.0553.v1

Hif-Prolyl Hydroxylase Domain Proteins (Phds) in Cancer – Potential Targets for Anti-Tumor Therapy?

Diana Gaete, Diego Rodriguez, Deepika Watts, Sundary Sormendi, Triantafyllos Chavakis, Ben Wielockx

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: hypoxia; tumor; PHD; HIF

Online: 22 December 2020 (10:46:28 CET)

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Preprint REVIEW | doi:10.20944/preprints202304.0094.v1

SUMOtherapeutics for Ischemic Stroke

Paramesh Karandikar, Jakob Gerstl, Ari Kappel, Sae-Yeon Won, Daniel Dubinski, Monica Emili Garcia-Segura, Florian Gessler, Alfred Pokmeng See, Luca Peruzzotti Jametti, Joshua Bernstock

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: stroke; ischemia; neuroprotection; SUMOylation; experimental therapeutics

Online: 6 April 2023 (12:21:33 CEST)

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Preprint COMMUNICATION | doi:10.20944/preprints202303.0373.v1

Plasma Galectin-4 Levels are Increased after Stroke in Mice and Humans

Joao Vieira, Amra Jujic, Hana Matuskova, Peter M. Nilsson, Ulf Lindblad, Michael Hecht Olsen, João M.N. Duarte, Anja Meissner, Martin Magnusson

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: ischemia; cardiovascular disease; diabetes; obesity; galectins

Online: 21 March 2023 (07:56:47 CET)

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Preprint REVIEW | doi:10.20944/preprints202010.0136.v1

Hypoxia Pathway Proteins are Master Regulators of Erythropoiesis

Deepika Watts, Diana Gaete, Diego Rodriguez, David Hoogewijs, Martina Rauner, Sundary Sormendi, Ben Wielockx

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: hypoxia; erythropoiesis; EPO; HIF; CKD

Online: 6 October 2020 (15:41:14 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202312.0918.v1

Glutathione Non-covalent Binding Sites on Hemoglobin and Major Glutathionylation Target betaCys94 Are Conservative among Both Hypoxia-Sensitive and Hypoxia-Tolerant Mammal Species

Anastasia A. Anashkina, Sergey Yurievich Simonenko, Yury L. Orlov, Irina Yu. Petrushanko

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: hypoxia; hemoglobin; glutathione; redox sensitivity; hypoxia-tolerant species; alpha subunit; beta-subunit; cysteine residues

Online: 13 December 2023 (04:59:33 CET)

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Preprint ARTICLE | doi:10.20944/preprints202402.1027.v1

TRIM2 Selectively Regulates Inflammation-Driven Pathological Angiogenesis without Affecting Physiological Hypoxia-Mediated Angiogenesis

Nathan K.P. Wong, Emma L. Solly, Richard Le, Victoria A. Nankivell, Jocelyne Mulangala, Peter J. Psaltis, Stephen J. Nicholls, Martin K.C. Ng, Christina A. Bursill, Joanne T.M. Tan

Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: Inflammation; Ischemia; Neovascularization; HIF-1α ; eNOS

Online: 19 February 2024 (08:33:17 CET)

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Preprint CASE REPORT | doi:10.20944/preprints202311.1336.v1

Pneumatosis Intestinalis Concurrent with Superior Mesenteric Artery Thrombosis: A Case Report

Parihar Doshi, Tushar Teraiya, Vismit Gami, Sahil Shah, Dev Desai

Subject: Medicine And Pharmacology, Gastroenterology And Hepatology Keywords: Pneumatosis intestinalis; Thrombosis; CT Scan; Atherosclerosis; Ischemia

Online: 21 November 2023 (13:43:57 CET)

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Preprint REVIEW | doi:10.20944/preprints202311.0909.v1

A Review of the Scope of Wearable Ultrasonic Sensors for Ischemia Monitoring

Evan Brophy, Masudul Imtiaz

Subject: Engineering, Electrical And Electronic Engineering Keywords: Blood Pressure; Ischemia Monitoring; Wearable Ultrasonic Sensor

Online: 15 November 2023 (03:51:00 CET)

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Preprint ARTICLE | doi:10.20944/preprints202303.0444.v1

The Matrix Receptor CD44 Is Present in Astrocytes Throughout the Human CNS and Accumulates in Hypoxia and Seizures

Osama Al Dalahmah, Alexander A Sosunov, Yu Sun, Yang Liu, Nsikan Akpan, Nacoya Madden, E. Sander Connolly, Carol M Troy, Guy M McKhann II, James E. Goldman

Subject: Medicine And Pharmacology, Urology And Nephrology Keywords: CD44; astrocytes; hypoxia; seizures; interlaminar astrocytes

Online: 27 March 2023 (04:19:41 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202110.0386.v1

Causes and Treatment of Hypoxia During Total Hip Arthroplasty in Elderly Patients: Case Report

Jae Young Ji, Jin Hun Chung, Nan Seol Kim, Yong Han Seo, Ho Soon Jung, Hea Rim Chun, Hyung Yoon Gong, Woo Jong Kim, Jae Min Ahn, Yu Jun Park

Subject: Medicine And Pharmacology, Anesthesiology And Pain Medicine Keywords: Atelectasis; Hypoxia; Old age; Spontaneous respiration

Online: 26 October 2021 (12:36:47 CEST)

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Preprint REVIEW | doi:10.20944/preprints202401.0975.v1

Cellular Senescence, Mitochondrial Dysfunction, and Their Link to Cardiovascular Disease

Maria Camacho-Encina, Laura K Booth, Rachael Redgrave, Omowumi Folaranmi, Gavin David Richardson

Subject: Biology And Life Sciences, Aging Keywords: mitochondrial dysfunction; senescence; cardiac; cardiomyocyte; cardiac ischemia reperfusion

Online: 12 January 2024 (04:06:44 CET)

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Preprint REVIEW | doi:10.20944/preprints202102.0289.v1

Post Stroke Depression to be Expected

Tissa Wijeratne, Carmela Sales

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Cytokine, Depression, Ischemia, Stroke, Apoptosis, Excitotoxicity, Onecosis, Inflammation,

Online: 11 February 2021 (16:46:06 CET)

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Preprint ARTICLE | doi:10.20944/preprints202305.2144.v1

SIRT5 Activation and Inorganic Phosphate Binding Reduce Cancer Cells Vitality by Modulating Autophagy/Mitophagy and ROS

Federica Barreca, Michele Aventaggiato, Laura Vitiello, Luigi Sansone, Matteo Antonio Russo, Antonello Mai, Sergio Valente, Marco Tafani

Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: Autophagy; Mitophagy; ROS; Sirtuins; Glutamine; Glutaminase; Hypoxia

Online: 30 May 2023 (12:51:57 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202208.0462.v1

Small Extracellular Vesicles from Hypoxic Triple-Negative Breast Cancer Cells induce Oxygen-dependent Cell Invasion

Bianca Cruz Pachane, Ana Carolina Caetano Nunes, Thais Regiani Cataldi, Kelli Cristina Micocci, Bianca Caruso Moreira, Carlos Alberto Labate, Heloisa Sobreiro Selistre-de-Araujo, Wanessa Fernanda Altei

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Hypoxia; Extracellular vesicles; Breast Cancer; Cell Invasion

Online: 26 August 2022 (14:08:23 CEST)

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Preprint CONCEPT PAPER | doi:10.20944/preprints202206.0145.v1

Mirage or Miracle—Intraovarian Autologous Platelet Cytokines for Infertility and Menopause

E. Scott Sills

Subject: Medicine And Pharmacology, Obstetrics And Gynaecology Keywords: ovary; PRP; senescence; rejuvenation; hypoxia; telomere length

Online: 9 June 2022 (11:16:03 CEST)

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Working Paper ARTICLE

Exogenous H2S Regulates the Expression of Cystathionine Gamma-Lyase in HUVECs During Hypoxia

Maoxian Wang

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Cystathionine gamma-lyase; Hydrogen sulfide; Hypoxia; HUVECs

Online: 23 June 2021 (11:51:08 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202104.0265.v1

HIF3A: A Potent Prognostic Biomarker in Different Kinds of Cancer

Behnaz Yazdani, Hajar Sirous

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: cancer; hypoxia-inducible factors; HIF3A; expression analysis

Online: 9 April 2021 (14:35:55 CEST)

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Background: Hypoxia-inducible factors (HIFs) are transcription factors that get activated and stabilized in the heterodimerized form under hypoxic conditions. The three members of the HIF alpha factors share high structural similarity but have tissue-specific expression patterns. A majority of studies have reported the importance of the HIF1A and HIF2A activity in the survival, proliferation, metastatic potential, and metabolic regulation of hypoxic cancer cells. However, the importance of the expression pattern and activity of HIF3A in a variety of cancers remains unknown. Method and materials: The expression profile of 13 different types of The Cancer Genome Atlas (TCGA) cancer samples were downloaded, normalized and differential gene expression analysis (DGE) was performed to compare the expression pattern of HIF alpha family members in cancer and adjacent normal tissues, as well as at different stages and tumor-sizes. Receiver operating characteristic (ROC) test and survival analysis were carried out to estimate the diagnostic potential of HIF alpha isomers in different cancers, as well as the survival rate of patients with the varying expression levels of HIF alpha factors. Results: The expression status of HIF3A was notably less in all cancer samples in contrast to their adjacent normal tissues. The expression degree of HIF1A varied among distinct types of cancer and the expression degree of HIF2A was lower in nearly all types of cancers. The expression level of HIF alpha isomers did not significantly correlate with different sizes of tumor samples and stages of different tumor tissue samples. HIF3A had very weak diagnostic potential, while HIF2A had better diagnostic potential in most types of cancers compared to HIF1A. Patients who had a higher level of HIF3A had better survival, while the higher expression levels of HIF1A and HIF2A were associated with worse survival in many types of cancers. Conclusion: Our study shows the heterogenous expression pattern of HIF alpha subunits in distinctive kinds of cancers and the influence of HIF3A expression level in the survival of patients with varying types of cancers.

Preprint ARTICLE | doi:10.20944/preprints202102.0332.v3

Endothelial Autocrine Signaling through CXCL12/CXCR4/FoxM1 Axis Contributes to Severe Pulmonary Arterial Hypertension

Dan Yi, Bin Liu, Ting Wang, Qi Liao, Maggie M. Zhu, You-Yang Zhao, Zhiyu Dai

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Angiogenesis; Pulmonary hypertension; Endothelium; PHD2 Deficiency; Hypoxia

Online: 22 March 2021 (15:51:47 CET)

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Preprint ARTICLE | doi:10.20944/preprints202011.0198.v1

Using of Animal Models of Angiogenesis to Confirm a Bidens pilosa-Sourced Polyacetylenic Glucoside Inhibits Angiogenesis Targeting Hypoxia through VEGF and PDIA4 Suppression

Cheng-Ying Yang, Jhih-Ying Wong, Chuen-Fu Lin, Chih-Yu Chang, Cicero Lee-Tian Chang

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: angiogenesis; Bidens pilosa; cancer; hypoxia; PDIA4; VEGF

Online: 4 November 2020 (15:20:10 CET)

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Simply Summary: Translation of new cancer treatments between pets and human were noticed in comparative oncological investigation. The current study aims at evaluating a polyacetylenic glucoside purified from an edible herb, Bidens pilosa, to present its anti-angiogenic effects. We innovatively find this polyacetylenic glucoside, cytopiloyne, shows anti-angiogenic effect on different in vitro assays and various in vivo animal models under hypoxia. Based on results of this study, cytopiloyne will be a prospective herb angiogenesis inhibitor candidate to control animal or human cancer formation as adjuvant therapy. Abstract: Anti-angiogenesis is a pivotal combination treatment approach in cancer therapy but rare using on companion animals. This study aimed at evaluating the anti-angiogenic effect of a B. pilosa sourced polyacetylenic glucoside, cytopiloyne, on various in vitro assays and in vivo models. We provide evidences showing that CP has anti-angiogenic activities. Firstly, CP inhibited sponge/ Matrigel plug angiogenesis from tumor cells and decreased the survival of tumor cells on hypoxic conditions. Besides, CP declined PKCα protein expression which a protein leads to the growth and spread of tumors under hypoxia. Secondly, inhibitory effects of CP on endothelial angiogenesis were confirmed by chick chorioallantoic membrane assay, tube formation of SVEC4-10 cells and Matrigel plug assay. A dose-dependent CP treatment inhibited 4T1 cells proliferation under hypoxia and migration. It also suppresses VEGF transcription under hypoxia. Finally, we found that CP decreased PDIA4, a novel regulator of cancer growth, expression in endothelial cells. This effect was confirmed by PDIA4 knockout mice with reduced angiogenesis in Matrigel plug assay. Taken together, these results suggest that CP might act as a promising anti-angiogenic herbal agent candidate to be used in animal hypervascularized cancer of veterinary medicine or in combination to control human cancer as adjuvant therapy.

Preprint ARTICLE | doi:10.20944/preprints201806.0325.v1

Effects of Acute Hypoxic Provocation on Autonomic Nervous System in Young “Healthy” Smokers Measured by Heart Rate Variability

Zdravko Taralov, Peter Dimov, Kiril Terziyski, Blagoi Marinov, Mariyan Topolov, Stefan Kostianev

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: heart rate variability, smoking, hypoxia, autonomic dysfunction

Online: 20 June 2018 (15:38:52 CEST)

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Background and objectives: Smoking leads to autonomic dysfunction. However, the clinical methods for diagnosing this dysfunction are not sufficient. Since exogenous hypoxia leads to changes in the autonomic cardiac control, the aim of our study was to compare the activity of the autonomic nervous system via heart rate variability (HRV) in young “healthy” smokers and non-smokers before, during and after a short-term exogenous hypoxic exposure. Methods: Twenty-one healthy non-smoking males aged 28.0±7.4 (mean±SD) and fourteen healthy smoking males aged 28.1±4.3 with 9.2±5.6 pack-years were subjected to one-hour hypoxic exposure (FiО2=12.3±1.5%) via hypoxicator (AltiPro 8850 Summit+, Altitude Tech, Canada) with simultaneous recording of electrocardiography and pulse oximetry. HRV data was derived via specific software (Kubios HRV, Finland) by analyzing the pre-hypoxic, hypoxic and post-hypoxic periods. Results: Standard deviation of the intervals between normal beats (SDNN) was higher in non-smokers in the pre-hypoxic period (62.0±32.1 vs 40.3±16.2, p=0.013) but not in hypoxia (75.7±34.8 vs 57.9±18.3, p=0.167). When comparing intragroup HRV changes of shifting from hypoxic to post-hypoxic (normoxic) conditions we found that there is a significant increase in the root mean square of successive RR interval differences (RMSSD) (65.9±40.2 vs 75.1±45.9, p=0.011) and in the high frequency (lnHF) (6.8±1.4 vs 7.2±1.3, p=0.014) and a decrease in LF/HF (3.0±2.3 vs 1.9±1.5, p<0.001), but these changes were observed only in the group of non-smokers. Conclusions: Smoking likely impairs autonomic regulation in young healthy males and may lead to a decreased HRV even before subjective clinical signs and symptoms. Hypoxic exposure test could be applied in clinical practice for early detection of autonomic dysfunction in smokers, because their parasympathetic reactivation is blunted when shifting from hypoxic to normoxic ambient conditions measured by HRV.

Preprint ARTICLE | doi:10.20944/preprints201710.0034.v2

Pharmacokinetics and Scintigraphic Imaging of the Hypoxia-Imaging Agent [¹²³I]IAZA in Healthy Adults Following Exercise-Based Cardiac Stress

Daria Stypinski, Stephen A McQuarrie, Alexander JB McEwan, Leonard I Wiebe

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: pharmacokinetics; radiotracers; hypoxia; nuclear imaging; [123I]IAZA

Online: 24 February 2018 (07:21:45 CET)

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The objective of this work is to evaluate the potential effect of cardiac stress exercise on the accumulation of [¹²³I]IAZA, a radiopharmaceutical used to image focal tissue hypoxia, in otherwise normal myocardium in healthy volunteers, and to determine the impact of exercise on [¹²³I]IAZA pharmacokinetics. The underlying goal is to establish a rational basis and a baseline for studies of focal myocardial hypoxia in cardiac patients using [¹²³I]IAZA. Three healthy male volunteers ran the ‘Bruce’ treadmill protocol, a clinically-accepted protocol designed to expose myocardial ischemia in patients. The ‘Bruce’ criterion heart rate is 85% of [220 – age]. Approximately one minute before reaching this level, [¹²³I]IAZA (5.0 mCi/0.85 mg) was administered as a slow (1–3 min) single intravenous (i.v.) injection via an indwelling venous catheter. The volunteer continued running for an additional 1 min before being transferred to a gamma camera. Serum samples were collected from the arm contralateral to the administration site at pre-determined intervals from 1 min to 45 h post injection and were analyzed by radio HPLC. Pharmacokinetic (PK) parameters were derived for [¹²³I]IAZA and total radioactivity (total[¹²³I]) using compartmental and noncompartmental analyses. Whole-body planar scintigraphic images were acquired from 0.75 to 24 h after dosing. PK data and scintigraphic images were compared to previously published [¹²³I]IAZA data from healthy volunteers rest. Following exercise stress, both [¹²³I]IAZA and total[¹²³I] exhibited bi-exponential decline profiles, with rapid distribution phases [half-lives (t_1/2α) of 1.2 and 1.4 min, respectively], followed by slower elimination phases [t_1/2β of 195 and 290 min, respectively]. Total body clearance (CL_TB) and the steady state volume of distribution (V_ss) were 0.647 L/kg and 185 mL/min, respectively, for [¹²³I]IAZA and 0.785 L/kg and 135 mL/min, respectively, for total[¹²³I]. The t_1/2β, CL_TB and V_ss values were comparable to those reported previously for rested volunteers. The t_1/2α was approximately 4-fold shorter for [¹²³I]IAZA and approximately 3-fold shorter for total[¹²³I] under exercise relative to rested subjects. The heart region was visualized in early whole body scintigraphic images, but later images showed no accumulated radioactivity in this region, and no differences from images reported for rested volunteers were apparent. Minimal uptake of radiotracer in myocardium and skeletal muscle was consistent with uptake in non-stressed myocardium. Whole-body scintigrams for [¹²³I]IAZA in exercise-stressed healthy volunteers were indistinguishable from images of non-exercised volunteers. There was no evidence of hypoxia-dependent binding in exercised but otherwise healthy myocardium, supporting the conclusion that exercise stress at Bruce protocol intensity does not induce measurable myocardial hypoxia. Effects of exercise on PK parameters were minimal; specifically, the t_1/2α was shortened, reflecting increased cardiac output associated with exercise. It is concluded that because [¹²³I]IAZA was not metabolically bound in exercise-stressed myocardium, a stress test will not create elevated myocardial background that would mask regions of myocardial perfusion deficiency. [¹²³I]IAZA would therefore be suitable for the detection of viable, hypoxic myocardium in patients undergoing stress-test-based diagnosis.

Preprint ARTICLE | doi:10.20944/preprints202202.0349.v1

Identification of Novel Direct Small-Molecule Inhibitors against HIF-2A using Structure-based Virtual Screening and Molecular Dynamics Simulation

Behnaz Yazdani, Peter A.C. Wing, Francisco J. Enguita, Hajar Sirous

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Hypoxia-inducible factor; cancer; hypoxia; drug discovery; medicinal chemistry; virtual screening; molecular dynamics simulation; MM-PBSA; Drug discovery

Online: 28 February 2022 (08:40:24 CET)

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Preprint REVIEW | doi:10.20944/preprints202404.0575.v1

Cannabinoids and Cardiac Rhythms: Unveiling the Relationship between Cannabis Use, ECG Changes, and Arrhythmias

Behzad Fahimi, Somayeh Beikmohammadi, Parsa Rostami

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Cannabis; Electrocardiogram (ECG); Arrhythmias; Myocardial ischemia; Cardiac ion channels

Online: 8 April 2024 (15:02:42 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202402.1406.v1

Could Phosphorous MR Spectroscopy Help Predict the Severity of Vasospasm? A Pilot Study

Malik Galijasevic, Ruth Steiger, Stephanie Alice Treichl, Wing Man Ho, Stephanie Mangesius, Valentin Ladenhauf, Johannes Deeg, Leonhard Gruber, Miar Ouaret, Milovan Regodic, Lukas Lenhart, Bettina Pfausler, Astrid Ellen Grams, Ondra Petr, Claudius Thomé, Elke Ruth Gizewski

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: subarachnoidal hemorrhage, brain aneurysm, phosphorous spectroscopy, vasospasm, delayed ischemia

Online: 26 February 2024 (09:42:36 CET)

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Preprint ARTICLE | doi:10.20944/preprints202212.0152.v1

Eugenio Martelli, Matilde Zamboni, Giovanni Sotgiu, Laura Saderi, Massimo Federici, Giuseppe Massimo Sangiorgi, Mariangela Valentina Puci, Allegra Rosa Martelli, Teresa Messina, Paolo Frigatti, Maria Pia Borrelli, Carlo Ruotolo, Ilaria Ficarelli, Paolo Rubino, Francesco Pezzo, Luciano Carbonari, Andrea Angelini, Edoardo Galeazzi, Luca Calia Di Pinto, Franco Michelino Fiore, Armado Palmieri, Giorgio Ventoruzzo, Giulia Mazzitelli, Franco Ragni, Antonio Bozzani, Enzo Forliti, Claudio Castagno, Pietro Volpe, Mafalda Massara, Diego Moniaci, Elisa Pagliasso, Tania Peretti, Mauro Ferrari, Nicola Troisi, Pietro Modugno, Maurizio Maiorano, Umberto Marcello Bracale, Marco Panagrosso, Mario Monaco, Giovanni Giordano, Giuseppe Natalicchio, Antonella Biello, Giovanni Maria Celoria, Alessio Amico, Mauro Di Bartolo, Massimiliano Martelli, Roberta Munaó, Davide Razzano, Giovanni Colacchio, Francesco Bussetti, Gaetano Lanza, Antonio Cardini, Bartolomeo Di Benedetto, Mario De Laurentis, Maurizio Taurino, Pasqualino Sirignano, Pierluigi Cappiello, Andrea Esposito, Santi Trimarchi, Silvia Romagnoli, Andrea Padricelli, Giorgio Giudice, Adolfo Crinisio, Giovanni Di Nardo, Giuseppe Battaglia, Rosario Tringale, Salvatore De Vivo, Rita Compagna, Valerio Stefano Tolva, Ilenia D'Alessio, Ruggiero Curci, Simona Giovannetti, Giuseppe D'Arrigo, Giusi Basile, Dalmazio Frigerio, Gian Franco Veraldi, Luca Mezzetto, Arnaldo Ippoliti, Fabio Massimo Oddi, Alberto Maria Settembrini

Subject: Medicine And Pharmacology, Hematology Keywords: chronic limb-threatening ischemia; outcome; sex; age; limb salvage

Online: 8 December 2022 (09:39:30 CET)

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Preprint ARTICLE | doi:10.20944/preprints202104.0205.v1

Different Lower Extremity Arterial Calcification Patterns in Patients with Chronic Limb-Threatening Ischemia Compared with Asymptomatic Controls

Louise CD Konijn, Richard AP Takx, Willem PThM Mali, Hugo TC Veger, Hendrik van Overhagen

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: chronic limb-threatening ischemia; peripheral arterial disease; calcification pattern

Online: 7 April 2021 (14:45:17 CEST)

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Objectives The most severe type of peripheral arterial disease (PAD) is critical limb ischaemia (CLI). In CLI, calcification of the vessel wall plays an important role in symptoms, amputation rate and mortality. However, calcified arteries are also found in asymptomatic persons (non-PAD patients). We investigated whether the calcification pattern in CLI patients and non- PAD patients are different and could possibly explain the symptoms in CLI patients. Materials and Methods 130 CLI and 204 non-PAD patients underwent a CT of the lower extremities. This resulted in 118 CLI patients (mean age 72±12, 70.3% male) that were age-matched with 118 non-PAD patients (mean age 71±11, 51.7% male). The characteristics severity, annularity, thickness and continuity were assessed in the femoral and crural arteries and analysed by binary multiple logistic regression. Results Nearly all CLI patients have calcifications and these are equally frequent in the femoropopliteal (98.3%) and crural arteries (97.5%), while the non-PAD patients had in just 67% any calcifications with more calcifications in the femoropopliteal (70.3%) than in the crural arteries (55.9%, p<0.005). The crural arteries of the CLI patients had significantly more complete annular calcifications (OR 2.92, p=0.001.) while in the non-PAD patients dot-like calcifications dominated. In CLI patients, the femoropopliteal arteries had more severe, irregular / patchy and thick calcifications (OR 2.40, 3.27, 1.81, p≤0.05, respectively) while in non-PAD patients, thin continuous calcifications prevailed. Conclusions Compared with non-PAD patients CLI patients are more frequently and extensively calcified. Annular calcifications were found in the crural arteries of CLI patients while dot-like calcifications were mostly present in the non-PAD patients. These different patterns of calcifications in CLI point at different etiology and can have prognostic and eventually therapeutic consequences.

Preprint ARTICLE | doi:10.20944/preprints202302.0425.v1

Obstructive Sleep Apnea as a Cause of Gout

Burton Abrams, Peter Delannoy, Richard Johnson

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: sleep apnea; hypoxia; gout; hyperuricemia; urate; metabolic comorbidities

Online: 24 February 2023 (09:31:14 CET)

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Preprint ARTICLE | doi:10.20944/preprints202208.0043.v1

Upregulation of Cytoglobin in 3D-cultures of Head and Neck Cancer Cells: Role of Hypoxia and Implications for Cisplatin Resistance

Garret Rochford, Rameeza Basar, Rose Dhiman, Djeren Simitdjioglu, Lorna S Thorne, Lakis Liloglou, Janet M. Risk, Nikolas J Hodges

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: cytoglobin; spheroids; hypoxia; HIF1A; head and neck cancer

Online: 2 August 2022 (06:23:18 CEST)

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Cytoglobin has been implicated in a range of pathological conditions including fibrosis and cancer, where cytoglobin expression is linked to hypoxia- and drug-resistance. One disease where there is evidence of a role for cytoglobin is head and neck squamous cell carcinoma, a disease with a poor prognosis and where clinical resistance to platinum-based drugs is common. In the current study, we demonstrate that 3D-culture of head and neck cancer cells (PE/CA-PJ41, Liv-22K) and normal oral keratinocyte cells (NOK-hTERT) results in changes in sensitivity to cisplatin cytotoxicity compared to 2D-cultures. Relative to 2D-cultures, 3D-cultures of PE/CA-PJ41 and NOK-hTERT cells demonstrated increased cisplatin resistance. In contrast, 3D-cultures of Liv-22K cells were more sensitive to cisplatin. Evidence for cisplatin genotoxicity was observed in the form of GADD45A activation in PE/CA-PJ41 cells but not the other two cell types investigated. Furthermore, DNA-strand breaks were also detected by the alkaline comet assay in PE/CA-PJ41 cells although levels were not significantly affected by 3D-culture. Cytoglobin expression levels were elevated by 3D-culture in all three cell lines investigated and there were also changes in expression of genes related to cell division (MKI57, GJB6), cell adhesion (CDH1), stress response (NFkB, NQO1) and apoptosis (Casp3) but these changes were cell line specific. We also observed consistent transcriptional activation of HIF1a in 3D-cultures of all three cell lines, suggestive of hypoxic conditions in spheroids. In support of a direct role of hypoxia in cytoglobin induction, the HIF1a stabiliser cobalt chloride also induced cytoglobin expression in spheroids. Transcriptomic profiling of PE/CA-PJ41 cells over-expressing cytoglobin identified 121 differentially regulated genes, when cells were cultured under hypoxic conditions. Major changes identified included, upregulation of G1/S cell cycle regulation as well as wnt- and RhoGTPase-signalling pathways. In conclusion, 3D-cultures are a useful model to further study the biological function of cytoglobin in head and neck cancer and we provide evidence that further supports a role for cytoglobin in hypoxia-dependent cellular proliferation and phenotypic changes that could contribute to cisplatin resistance in vivo.

Working Paper ARTICLE

Calcineurin Suppresses Cardiomyocyte-protective Autophagy Under Chronic Intermittent Hypoxia by Downregulating the AMPK Pathway

Sheng Xie, Wei Liu, Meng Jin, Xiaochen Li, Tao Wang, Shaolin Zeng, Hanxiang Nie, Zhao Dong, Zhenghua Ke, Ke Hu

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: chronic intermittent hypoxia; autophagy; apoptosis; cardiomyocyte damage; calcineurin

Online: 24 June 2021 (14:58:22 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202104.0359.v1

PBRM1 Cooperates with YTHDF2 to Control HIF-1Alpha Protein Translation

Alena Shmakova, Mark Frost, Niall S Kenneth, Sonia Rocha

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: PBRM1; HIF-1; SWI/SNF; YTHDF2; m6A; Hypoxia.

Online: 13 April 2021 (13:24:41 CEST)

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Preprint REVIEW | doi:10.20944/preprints202011.0651.v1

Roles Of HIF and 2-Oxoglutarate Dependent Enzymes in Controlling Gene Expression In Hypoxia

Julianty Frost, Mark Frost, Michael Batie, Hao Jiang, Sonia Rocha

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: hypoxia; 2-OG dioxygenases; chromatin; transcription, translation; cancer

Online: 25 November 2020 (16:09:12 CET)

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Preprint ARTICLE | doi:10.20944/preprints201912.0280.v1

Pulmonary Hypertension Remodels the Genomic Fabrics of Major Functional Pathways

Rajamma Mathew, Jing Huang, Sanda Iacobas, Dumitru Iacobas

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: aerobic glycolysis; caveolin1; hypoxia; monocrotaline; oxidative phosphorylation; RhoA

Online: 21 December 2019 (10:48:00 CET)

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Preprint CASE REPORT | doi:10.20944/preprints202401.1796.v1

Retrograde Endovascular Recanalization of the Superior Mesenteric Artery for the Treatment of Acute Bowel Ischemia: Case Report

Pawel Latacz, Piotr Piekorz, Marian Simka

Subject: Medicine And Pharmacology, Emergency Medicine Keywords: acute bowel ischemia; mesenteric artery occlusion; mesenteric artery stenting; retrograde

Online: 25 January 2024 (07:12:18 CET)

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Preprint ARTICLE | doi:10.20944/preprints202401.0774.v1

Myocardial Perfusion Imaging and C-reactive Protein in Myo-Cardial Ischemia: A Retrospective Single-Center Study

Aidonis Rammos, Aris Bechlioulis, Areti Kekiopoulou, Pavlos Kekiopoulos, Christos S. Katsouras, Chrissa Sioka

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: C-reactive protein; ischemia; SPECT; myocardial perfusion imaging; cardiac imaging

Online: 10 January 2024 (10:08:28 CET)

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Preprint REVIEW | doi:10.20944/preprints202312.1073.v1

Prospects of Intravenous CoenzymeQ10 Administration in Emergency Ischemic Conditions

Elena Igorevna Kalenikova, Evgeniya Aronovna Gorodetskaya, Oxana Viktorovna Povarova, Oleg Stefanovich Medvedev

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: coenzyme Q10; ubiquinol; ubiquinone; brain ischemia; myocardial infarct; intravenous administration

Online: 14 December 2023 (09:10:35 CET)

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Preprint ARTICLE | doi:10.20944/preprints202311.1124.v1

Cardioprotective Effect of Epiisopiloturine, an Imidazole Alkaloid from Pilocarpus microphyllus, in Rats Submitted to Cardiac Ischemia and Reperfusion

Pedro Ivo De Marqui Moraes, Fernando Sabia Tallo, Rildo Yamaguti Lima, Sandra Augusta Gordinho Pinto, Erisvaldo Amarante De Araújo, Rodrigo de Barros Freitas, Carolina Trabasso Ferraz De Oliveira, Giovanna Seto De Oliveira, João Vitor Gardelli Trindade, Alexia Nascimento Arias, Rafael Batman de Góes, Carlos Eduardo Braga Filho, Jand Venes Rolim Medeiros, Lucas Antonio Duarte Nicolau, Leiz Maria Costa Véras, Monica Noleto Miranda, Almir Gonçalves Wanderley, Afonso Caricati-Neto, Francisco Sandro Menezes-Rodrigues

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Cardiac Diseases; Cardiac Ischemia-Reperfusion; Myocardial Infarction; Pharmacological Cardioprotection; Epiisopiloloturine

Online: 17 November 2023 (05:22:27 CET)

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Preprint REVIEW | doi:10.20944/preprints202308.0327.v1

The Interplay between Mitochondrial dysfunction and Ferroptosis during Ischemia-associated Central Nervous System Diseases

Heyan Tian, Boyang Huang, Huifang Nie, Xiangyu Chen, Yue Zhou, Tong Yang, Shaowu Cheng, Zhigang Mei, Jinwen Ge

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: cerebral ischemia; central nervous system diseases; mitochondrial dysfunction, ferroptosis; therapeutics

Online: 4 August 2023 (11:02:35 CEST)

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Cerebral ischemia, which is a leading cause of disability and mortality worldwide, sets off a chain of molecular and cellular pathologies that are associated with some central nervous system (CNS) disorders, mainly including ischemic stroke, Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy and other CNS diseases. In recent times, despite significant advancements in the treatment of the pathological processes underlying various neurological illnesses, effective therapeutic approaches specifically targeted at minimizing the damage of such diseases remain absent. Remarkably, ischemia causes severe damage to cells in Ischemia-associated CNS Diseases. Cerebral ischemia initiates oxygen and glucose deprivation, which subsequently promotes mitochondrial dysfunction, including MPTP opening, mitophagy dysfunction, and excessive mitochondrial fission, triggering various forms of cell death, such as autophagy, apoptosis, as well as ferroptosis. Ferroptosis, a novel type of regulated cell death (RCD), is characterized by iron-dependent accumulation of lethal reactive oxygen species and lipid peroxidation. Mitochondrial dysfunction and ferroptosis both play critical roles in the pathogenic progression of Ischemia-associated CNS Diseases. In recent years, growing evidence has indicated that mitochondrial dysfunction interplays with ferroptosis to aggravate cerebral ischemia injury. However, the potential connections between mitochondrial dysfunction and ferroptosis in Cerebral Ischemia have not yet been clarified. Thus, we analyze the underlying mechanism between mitochondrial dysfunction and ferroptosis in Ischemia-associated CNS Diseases. We also discovered that GSH depletion and GPX4 inactivation cause lipoxygenase activation and calcium influx following cerebral ischemia injury, resulting in MPTP opening and mitochondrial dysfunction. Additionally, dysfunction in mitochondrial electron transport and an imbalanced fusion-to-fission ratio can lead to the accumulation of reactive oxygen species and iron overload, which further contribute to the occurrence of ferroptosis. This creates a vicious cycle that continuously worsens cerebral ischemia injury. In this study, our focus is on exploring the interplay between mitochondrial dysfunction and ferroptosis, which may offer new insights into potential therapeutic approaches for the treatment of Ischemia-associated CNS Diseases.

Preprint REVIEW | doi:10.20944/preprints202306.2174.v1

The Effect of Andrographis paniculata and Its Derivatives in Neurodegenerative Diseases and Neuroinflammation

Francesca Bosco, Stefano Ruga, Rita Citraro, Antonio Leo, Lorenza Guarnieri, Jessica Maiuolo, Francesca Oppedisano, Roberta Macrì, Federica Scarano, Saverio Nucera, Irene Bava, Ernesto Palma, Carolina Muscoli, Juan Hancke, Giovambattista De Sarro, Vincenzo Mollace

Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: Andrographis paniculata; Andrographolide; Neurodegenerative Diseases; Alzheimer; Parkinson; Brain Ischemia; Neuroinflammation

Online: 30 June 2023 (07:38:39 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202201.0065.v1

Disassembly and Mislocalization of AQP4 in Incipient Scar Formation After Experimental Stroke

Shervin Banitalebi, Nadia Skauli, Samuel Geiseler, Ole Petter Ottersen, Mahmood Amiry-Moghaddam

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Aquaporin-4; AQP4ex; Stroke; Ischemia; Astrocyte; Astrogliosis; Glial scar; Neuroinflammation

Online: 6 January 2022 (10:16:02 CET)

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Working Paper ARTICLE

Local Anesthetic Delivered With a Dual Action Ring and Injection Applicator Numnuts® Reduces the Acute Pain Response of Lambs During Tail Docking

Alison Small, Danila Marini, Ian Colditz

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: analgesia; sheep; ischemia; latex ring; rubber ring; de-tailing; behavior.

Online: 1 June 2021 (09:50:27 CEST)

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Working Paper ARTICLE

Association of High Pre-Transplant Caveolin-1 Serum Concentrations with Attenuated Acute Cellular Rejection in Kidney Transplantation

Florian Emmerich, Stefan Zschiedrich, Christine Reichenbach-Braun, Caner Süsal, Susana Minguet, Marie-Christin Pauly, Maximilian Seidl

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Caveolin-1; kidney transplantation; graft rejection; ischemia; reperfusion injury (IRI)

Online: 1 December 2020 (14:08:33 CET)

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Preprint ARTICLE | doi:10.20944/preprints201806.0381.v1

CLINICAL PROFILE OF PATIENTS WITH CORONARY TORTUOSITY AND ITS RELATION WITH CORONARY ARTERY DISEASE

Ankush Gupta, Prashant Panda, YASH SHARMA, Ashwin Mahesh, Prafull Sharma, Nalin Kumar Mahesh

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: coronary tortuosity; myocardial ischemia; coronary artery disease; chronic stable angina.

Online: 25 June 2018 (11:02:03 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202404.0286.v1

Plant Biostimulants Enhance Bud Break in Vitis vinifera Crimson Seedless

Nicole C Venter, Eunice Avenant, Theunis Nicolaas Kotze, Paul Norman Hills, John Paul Moore

Subject: Biology And Life Sciences, Agricultural Science And Agronomy Keywords: Vitis vinifera, Crimson Seedless, bud break, plant biostimulant, hypoxia

Online: 3 April 2024 (11:56:31 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202404.0183.v1

Features of the Effect of Quercetin on Different Genotypes of Wheat under Hypoxia

Larisa Ivanovna Fedoreyeva, Elena Michailovna Lazareva, Neonila Vasilievna Kononenko

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Triticum aestivum; Triticum durum; hypoxia; quercetin; ROS; cytological analysis

Online: 2 April 2024 (10:38:27 CEST)

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Preprint REVIEW | doi:10.20944/preprints201703.0240.v1

Hypoxia and Inflammation in Cancer, Focus on HIF and NF-кB

Laura D'Ignazio, Michael Batie, Sonia Rocha

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: NF-кB, Hypoxia, Inflammation, IKK, PHDs, Cancer, TAK1, FIH

Online: 31 March 2017 (17:21:52 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202309.1325.v1

Pharmacological Modulation of the Ca2+/cAMP/Adenosine Signaling in Cardiac Cells as a New Cardioprotective Strategy to Reduce Severe Arrhythmias in Myocardial Infarction

Fernando Sabia Tallo, Patrícia Oliveira Santana, Sandra Augusta Gordinho Pinto, Rildo Yamaguti Lima, Erisvaldo Amarante De Araújo, José Gustavo Padrão Tavares, Marcelo Pires-Oliveira, Lucas Antonio Duarte Nicolau, Jand Venes Rolim Medeiros, Murched Omar Taha, André Ibrahim David, Bráulio Luna-Filho, Carlos Eduardo Braga Filho, Adriano Henrique Pereira Barbosa, Célia Maria Camelo Silva, Almir Gonçalves Wanderley, Adriano Mendes Caixeta, Afonso Caricat-Neto, Francisco Sandro Menezes-Rodrigues

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: cardiac ischemia-reperfusion; cardiac arrhythmias; pharmacological cardioprotection; Ca2+ channels; adenosine receptors

Online: 20 September 2023 (08:45:21 CEST)

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Working Paper REVIEW

Diabetic Cardiomyopathy and Ischemic Coronary Heart Disease: Prevention and Therapy by Exercise and Conditioning

Antonio Crisafulli, Pasquale Pagliaro, Silvana Roberto, Lucia Cugusi, Giuseppe Mercuro, Antigone Lazou, Cristophe Beauloye, Luc Bertrand, Derek Hausenloy, Manuela Aragno, Claudia Penna

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Diabetic Cardiomyopathy; Hyperglycemia; Ischemia/Reperfusion Injury; Metabolism; Mitochondria; Remote Conditioning; Exercise

Online: 17 March 2020 (08:52:25 CET)

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Preprint ARTICLE | doi:10.20944/preprints202404.0005.v1

Hypoxia in the Blue Mussel Mytilus chilensis Induces Transcriptome Shift Associated with Endoplasmic Reticulum Stress, Metabolism, and Immune Response.

Milton Gabriel Montúfar-Romero, Valentina Marjorie Valenzuela-Muñoz, Diego Andrés Valenzuela-Miranda, Cristian Jorge Gallardo-Escárate

Subject: Biology And Life Sciences, Aquatic Science Keywords: Bivalve mollusks, Hypoxia, Oxidative stress, Reoxygenation, Gills, Transcriptome, Metabolism, Immunity.

Online: 1 April 2024 (09:51:35 CEST)

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Preprint REVIEW | doi:10.20944/preprints202312.1697.v1

Interplay of Angiotensin Peptides, Vasopressin and Insulin in the Heart: Altered Interactions in Obesity and Diabetes Mellitus

Ewa Szczepańska-Sadowska

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Angiotensin; diabetes mellitus; heart failure; hypertension; hypoxia; insulin; obesity; vasopressin

Online: 22 December 2023 (08:12:34 CET)

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Preprint ARTICLE | doi:10.20944/preprints202312.1352.v1

Serelaxin Protects H9c2 Cardiac Myoblasts against Hypoxia and Reoxigenation-Induced Damage by Up-Regulation of AMPK/SIRT1: Further Insight into the Molecular Mechanisms of Cardioprotection of This Hormone

Virginia Zizi, Matteo Becatti, Daniele Bani, Silvia Nistri

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: Serelaxin; SIRT1; AMPK; hypoxia-reoxygenation; apoptosis; oxidative stress; H9c2 cells

Online: 19 December 2023 (05:17:43 CET)

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Preprint ARTICLE | doi:10.20944/preprints202312.0689.v1

A Data-Driven Framework for Clinical Decision Support Systems in Positive Airway Pressure and Oxygen Titration

Artis Svaza, Dana Zarina, Davis Freimanis, Pavels Osipovs, Svjatoslavs Kistkins, Vitalijs Ankudovics, Olegs Sabelnikovs, Valdis Pīrāgs, Yuriy Chizhov, Dmitrijs Bļizņuks

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: Markov decision processes; hypercapnia; hypoxia; PAP titration; Obstructive sleep apnea

Online: 11 December 2023 (14:59:47 CET)

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Background: Current obstructive sleep apnea treatment relies on manual PAP titration, but it has limitations. Complex interactions during titration and variations in SpO2 data accuracy pose challenges. Patients with co-occurring chronic hypercapnia may require precise oxygen titration. To address these issues, we propose a Clinical Decision Support System using Markov Decision Processes. Methods: This study, compliant with data protection laws, focused on adults with OSA-induced hypoxemia utilizing supplemental oxygen and CPAP/BiPAP therapy. PAP titration, conducted over one night, involved vigilant monitoring of vital signs and physiological parameters. Adjustments to CPAP pressure, potential BiLevel transitions, and supplemental oxygen were precisely guided by patient metrics. Markov Decision Processes outlined three distinct phases for sleep disorder management, incorporating expert medical insights. Results: In our study involving 14 OSA patients (average age: 63 years, 27% females, BMI 41 kg m−2), significant improvements were observed in key health parameters. The initial AHI of 61.8 events per hour significantly decreased to an average of 18.0 events per hour after PAP and oxygen titration (p < 0.0001), indicating a substantial reduction in sleep-disordered breathing severity. Concurrently, SpO2 levels increased significantly from an average of 79.7% before titration to 89.1% after titration (p < 0.0003). Pearson correlation coefficients demonstrated aggravation of hypercapnia in 50% of patients (N=5) with initial hypercapnia during the increase of CPAP pressure. However, transitioning to BiPAP exhibited a reduction in pCO2 levels, showcasing its efficacy in addressing hypercapnia. Simultaneously, BiPAP therapy correlated with a substantial increase in SpO2, underscoring its positive impact on oxygenation in OSA patients. Markov dynamic process analysis demonstrated realistic patient behavior during stable night conditions, emphasizing minimal apnea and good toleration to high CPAP pressure. Conclusions: the development of a framework for Markov Decision Processes of PAP and oxygen titration algorithms holds promise for providing algorithms for deviation in pCO2 and SpO2 markers. While challenges remain, including the need for high-quality data, the potential benefits in terms of patient management and care optimization are substantial, and this approach represents an exciting frontier in the realm of telemedicine and respiratory healthcare. Obstructive sleep apnea, PAP titration, hypoxia, hypercapnia, Markov decision processes

Preprint ARTICLE | doi:10.20944/preprints202309.1245.v1

Hypoxic Conditions Confer Chemoresistance to Crizotinib but not to Imatinib in Chronic Myeloid Leukemia (CML) Cells Depending on HIF1α and JAK2

Lena Avinery, Danielle Regev, Hazem Khamaisi, Jacob Gopas, Jamal Mahajna

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Hypoxia; CML; Bcr/Abl; chemoresistance; Imatinib; Crizotinib; 2-methoxyestradiol (2ME2)

Online: 20 September 2023 (07:48:05 CEST)

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Chronic myeloid leukemia (CML) is the most common form of leukemia in adults and accounts for approximately 15% of all leukemia cases. The etiology of this disease is based on the presence of the oncogenic Bcr/Abl fusion protein, which has dysregulated tyrosine kinase activity. This pathological condition is the result of a chromosomal translocation between chromosomes 9 and 22 leading to the formation of the Philadelphia chromosome (Ph). Clinical establishment of targeted therapy with Abl kinase inhibitors (AKIs) has been observed in the treatment of CML. Therapy resistance in patients with CML is due to genetic alterations in the cells of CML, specifically affecting the Bcr/Abl oncoprotein. Acquired resistance of CML patients to tyrosine kinase inhibitors (AKIs) has also been associated with the tumor microenvironment (TME). This study aimed to examine the role of hypoxic conditions in the development of chemoresistance to certain AKIs in CML. The findings of our study indicate that exposure to hypoxic conditions leads to a substantial increase in chemoresistance to crizotinib, while only resulting in a slight increase in chemoresistance to imatinib. It is worth noting that both drugs effectively block Bcr/Abl function. Furthermore, it was observed that the inclusion of the JAK1/2 inhibitor ruxolitinib resulted in an augmentation of chemoresistance to crizotinib in the context of hypoxia. Overexpression of hypoxia-inducible factor 1a (HIF1a) and silencing of JAK2 confirmed that the two proteins cooperate in mediating chemoresistance to crizotinib in CML cell lines. It is noteworthy that the compound 2-methoxy estradiol (2ME2), which is a metabolite of estradiol lacking estrogenic activity, has shown efficacy in reinstating the sensitivity of CML cells to crizotinib in the presence of hypoxic circumstances. Additionally, when used in conjunction with a JAK2 inhibitor, 2ME2 exhibited activity in restoring crizotinib sensitivity in CML cells. The findings of our study underscore the significance of selectively targeting elements of the HIF1α pathway in order to achieve total eradication of chronic myeloid leukemia (CML) cells.

Preprint ARTICLE | doi:10.20944/preprints202309.1256.v1

Hypoxic Conditions Confer Chemoresistance to Crizotinib but Not to Imatinib in Chronic Myeloid Leukemia (CML) Cells Depending on HIF1α and JAK2

Lena Avinery, Danielle Regev, Hazem Khamaisi, Jacop Gopas, Jamal Mahajna

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: hypoxia; CML; Bcr/Abl; chemoresistance; imatinib; crizotinib; 2-methoxyestradiol (2ME2)

Online: 19 September 2023 (07:23:27 CEST)

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Chronic myeloid leukemia (CML) is the most common form of leukemia in adults and accounts for approximately 15% of all leukemia cases. The etiology of this disease is based on the presence of the oncogenic Bcr/Abl fusion protein, which has dysregulated tyrosine kinase activity. This pathological condition is the result of a chromosomal translocation between chromosomes 9 and 22 leading to the formation of the Philadelphia chromosome (Ph). Clinical establishment of targeted therapy with Abl kinase inhibitors (AKIs) has been observed in the treatment of CML. Therapy resistance in patients with CML is due to genetic alterations in the cells of CML, specifically affecting the Bcr/Abl oncoprotein. Acquired resistance of CML patients to tyrosine kinase inhibitors (AKIs) has also been associated with the tumor microenvironment (TME). This study aimed to examine the role of hypoxic conditions in the development of chemoresistance to certain AKIs in CML. The findings of our study indicate that exposure to hypoxic conditions leads to a substantial increase in chemoresistance to crizotinib, while only resulting in a slight increase in chemoresistance to imatinib. It is worth noting that both drugs effectively block Bcr/Abl function. Furthermore, it was observed that the inclusion of the JAK1/2 inhibitor ruxolitinib resulted in an augmentation of chemoresistance to crizotinib in the context of hypoxia. Overexpression of hypoxia-inducible factor 1 (HIF1) and silencing of JAK2 confirmed that the two proteins cooperate in mediating chemoresistance to crizotinib in CML cell lines. It is noteworthy that the compound 2-methoxy estradiol (2ME2), which is a metabolite of estradiol lacking estrogenic activity, has shown efficacy in reinstating the sensitivity of CML cells to crizotinib in the presence of hypoxic circumstances. Additionally, when used in conjunction with a JAK2 inhibitor, 2ME2 exhibited activity in restoring crizotinib sensitivity in CML cells. The findings of our study underscore the significance of selectively targeting elements of the HIF1α pathway in order to achieve total eradication of chronic myeloid leukemia (CML) cells.

Preprint ARTICLE | doi:10.20944/preprints202308.0918.v1

Human Preadipocytes Differentiated under Hypoxia following PCB126 Exposure during Proliferation: Effects on Differentiation, Glucose Uptake and Adipokine Profile

Zeinab El Amine, Jean-François Mauger, Pascal Imbeault

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: hypoxia; polychlorinated biphenyl; inflammatory adipokines; human differentiated adipocytes; AhR; ARNT

Online: 11 August 2023 (09:55:08 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.0785.v1

Biocompatible Phosphorescent O2-sensors Based on Ir(III) Complexes for in vivo Hypoxia Imaging

Mozhgan Samandarsangari, Daria O. Kozina, Victor V. Sokolov, Anastasia D. Komarova, Marina V. Shirmanova, Ilya S. Kritchenkov, Sergey P. Tunik

Subject: Chemistry And Materials Science, Applied Chemistry Keywords: oxygen sensing; iridium complexes; phosphorescence; hypoxia; bioimaging; phosphorescence lifetime imaging

Online: 11 May 2023 (04:40:33 CEST)

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Preprint REVIEW | doi:10.20944/preprints202010.0055.v1

Carbon Ion Radiobiology

Walter Tinganelli, Marco Durante

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: carbon ions; particle therapy; radiotherapy; radiobiology; hypoxia; RBE; immunotherapy; metastasis

Online: 5 October 2020 (08:16:34 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201903.0087.v2

Energy Conversion Monitoring in Skin Tissue: A More Sensitive Measure of Hypoxia Occurring With Sleep Disordered Breathing Than Pulse Oximetry

Guy M. Hatch, Liza Ashbrook, Aric A. Prather, Andrew D. Krystal

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: tissue hypoxia; sleep disordered breathing; primary snoring; molecular tissue oximeter

Online: 16 August 2019 (06:27:46 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201811.0266.v1

Myocardial Interstitial Matrix as Novel Target for Succinic Acid Treatment Strategies during Experimental Hypobaric Hypoxia

Igor V. Zadnipryany, Tatiana P. Sataieva, Olga S. Tretiakova, Walery Zukow

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: hypobaric hypoxia; myocardium; interstitial space; fibroblasts; fibrosis; succinic acid; rats

Online: 12 November 2018 (05:16:27 CET)

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Preprint REVIEW | doi:10.20944/preprints201803.0004.v1

Hypoxia and Chromatin, a Focus on Transcriptional Repression Mechanisms

Michael Batie, Luis del Peso, Sonia Rocha

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: hypoxia; chromatin; transcriptional repression; repressor complexes; JmjC; histone methylation; HIF

Online: 1 March 2018 (06:36:57 CET)

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Preprint ARTICLE | doi:10.20944/preprints202312.1523.v1

Topical Application of Autologous Leukocyte-Rich Platelet-Rich Plasma with a High Concentration of Monocytes in Patients with Recalcitrant Ischemic Diabetic Foot Ulcers: Efficacy, Safety and Economic Evaluation.

Benedetta Ragghianti, Giovanni Antonio Silverii, Bianca Maria Berardi, Linda Luppichini, Maria Masulli, Matteo Monami

Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: Diabetes mellitus; Foot ulcer; Cell-therapy; Chronic Limb-Threatening Ischemia; Economic evaluation

Online: 20 December 2023 (10:18:08 CET)

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BACKGROUND: Patients with diabetic foot ulcers (DFU) and chronic limb-threatening ischemia (CLTI are at higher risk for major amputations and mortality. The aim of this study was to assess the safety and cost-efficacy of intramuscular injection of autologous monocyte-rich PRP platelet-rich plasma Tropocells® PRP (Estar Medical, Holon, Israel) in diabetic patients with chronic limb-threatening ischemia (CLTI) in which revascularization was not feasible. METHODS: a retrospective study was carried out on a series of patients with type 2 diabetes, grade Texas 3C or D DFU, and CLTI. All patients had undergone at least a previous revascularization and were allocated to a surgery waiting list for major amputation. According to the data provided by the manufacturer (https://www.zuccatobiotech.it/index.php/prodotti/tropocells), the monocyte-rich PRP kit obtained a platelet-rich plasma with a high concentration of peripheral blood mononuclear cells (with a proportionately lower amount of lymphocytes), a low concentration of neutrophils and an almost complete depletion of red blood cells. All patients underwent a procedure of local infiltration of autologous mononuclear cells through multiple perilesional and intramuscular injections of 10 mL PBMNC suspensions (0.2–0.3 mL in boluses) performed below the knee along the relevant vascular axis (anterior tibial artery and posterior tibial artery) at intervals of 1–2 cm and to a mean depth of 1.5–2 cm, using a 21 G needle. The procedures were performed according to the instructions of the manufacturer and were repeated at least two times (maximum 3 times) at intervals of 30 days. The principal endpoint was a composite of TcPO2 values at the first toe ≥30 mmHg and/or TcPO2 increase of at least 50% from baseline and/or ulcer healing. Secondary endpoints were individual components of the primary endpoint, quality of life, any adverse events, and direct costs. All the endpoints were evaluated at 26 weeks. RESULTS: Out of 21 enrolled patients, 13 (61.9%) reached the primary endpoint, whereas three patients underwent a major amputation, and two patients died. The median TpCO2 was significantly increased, and pain was significantly reduced. The overall mean and median cost per patient were 9,255±7,328€ and 4,001 [2,991;7,565]€, respectively. CONCLUSIONS: the use of PBMNCs implants in patients with DFU and no-option CLTI seems to be efficacious in reducing the risk of major amputation and improve ulcer healing.

Preprint REVIEW | doi:10.20944/preprints202312.0244.v1

Translational Relevance of Advanced Age and Atherosclerosis in Preclinical Trials of Biotherapies for Peripheral Artery Disease

Keith A Webster

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: gene therapy; cell therapy; peripheral artery disease; critical limb ischemia; clinical trials

Online: 5 December 2023 (14:44:09 CET)

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Preprint REVIEW | doi:10.20944/preprints202308.0558.v1

Necroptosis in Organ Transplantation: Mechanisms and Potential Therapeutic Targets

Yajin Zhao, Kimberly Main, Tanroop Aujla, Shaf Keshavjee, Mingyao Liu

Subject: Medicine And Pharmacology, Clinical Medicine Keywords: programmed cell death; donor organ condition; ischemia reperfusion injury; allograft rejection; inflammation

Online: 7 August 2023 (12:02:35 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202205.0184.v1

Amyloid Precursor Protein, Alpha-, Beta- and Gamma-Secretases Expression in Penumbra Cells after Photothrombotic Stroke. Evaluation of the Neuroprotective Effect of Secretase Inhibitors

Svetlana Sharifulina, Valeria Guzenko, Alexandr Logvinov, Andrey Khaitin, Yuliya Kalyuzhnaya, Natalia Dobaeva, Yan Li, Lei Chen, Вin He, Svetlana Demyanenko

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: amyloid precursor protein; photothrombotic stroke; ischemia; alpha-secretase; beta-secretase; gamma-secretase

Online: 13 May 2022 (08:39:09 CEST)

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Preprint CONCEPT PAPER | doi:10.20944/preprints202106.0486.v1

The Oxygen Transport Triad in High Altitude Pulmonary Edema: a Perspective from the High Andes

Gustavo Zubieta-Calleja, Natalia Zubieta-DeUrioste

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: high altitude, chronic hypobaric hypoxia, physiologic adaptation, travel to high altitude cities, high altitude physiology, pulmonary hypertension, lung disease, hemoglobin, tolerance to hypoxia, oxygen content.

Online: 18 June 2021 (15:22:04 CEST)

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Preprint BRIEF REPORT | doi:10.20944/preprints202003.0338.v3

Yin-Yang Balance of ACE/ACE2 Pathways: The Rational for Administration of ACE2 Pathway Inhibitors in Patients Infected by SARS-CoV-2

Loris Zamai

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Severe Acute Respiratory Syndrome Coronavirus-2; (soluble) ACE2; eosinophil; asthma; IL-10; Lung fibrosis; hypercapnic acidosis; hypoxia; infarction; hypertension; cardiac dysfunction; respiratory distress; coagulopathy; Angiotensin; renin; Ang (1-7); Ang (1-9); Mas receptor; AT2 receptor

Online: 6 May 2020 (04:40:25 CEST)

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Preprint REVIEW | doi:10.20944/preprints202310.0962.v1

NanoBubble-mediated Oxygenation: Elucidating the Underlying Molecular Mechanisms in Hypoxia and Mitochondrial-related Pathologies

Sergio M. Viafara-Garcia, Muhammad Saad Khan, Ziyad S. Haidar, Juan Pablo Acevedo Cox

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: oxygen; nanobubbles; hypoxia; mitochondria; metabolism, molecular; drug delivery; cancer, stress; innovation

Online: 16 October 2023 (11:09:22 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202308.0610.v1

The Effect of High-Intensity Interval Exercise on Short-Term Glycaemic Control, Serum Level of Key Mediator in Hypoxia and Pro-Inflammatory Cytokines in Patients with Type 1 Diabetes

Barbara Hall, Aleksandra Żebrowska, Marcin Sikora, Szymon Siatkowski, Anna Robins

Subject: Biology And Life Sciences, Endocrinology And Metabolism Keywords: type 1 diabetes; high-intensity interval exercise; glycaemic control; hypoxia; inflammation

Online: 8 August 2023 (10:18:30 CEST)

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