المؤلفون: İlayda Altınönder, Mustafa Kaya, Sibel P. Yentür, Arman Çakar, Hacer Durmuş, Gülçin Yegen, Berker Özkan, Yeşim Parman, Amr H. Sawalha, Guher Saruhan-Direskeneli

المصدر: Journal of Neuroinflammation, Vol 21, Iss 1, Pp 1-10 (2024)

مصطلحات موضوعية: Thymoma, Thymus, Myasthenia gravis, Hypoxia-inducible factor-1, Neurology. Diseases of the nervous system, RC346-429

الوصف: Abstract Myasthenia gravis (MG) is an immune-mediated disease frequently associated with thymic changes. Increased T helper 17 (Th17) cell activity and dysfunctional regulatory T (Treg) cells have been demonstrated in subgroups of MG. On the other hand, hypoxia-inducible factor 1 (HIF-1) has been shown to regulate the Th17/Treg balance by inducing Th17 differentiation while attenuating Treg development. To identify the underlying mechanisms of different thymic pathologies in MG development, we evaluated thymic samples from thymoma-associated myasthenia gravis (TAMG), MG with hyperplasia (TFH-MG) and thymoma without MG (TOMA) patients. Differential gene expression analysis revealed that TAMG and TFH-MG cells are associated with different functional pathways. A higher RORC/FOXP3 ratio provided evidence for Th17/Treg imbalance in TAMG potentially related to increased HIF1A. The hypoxic microenvironment in thymoma may be a driver of TAMG by increasing HIF1A. These findings may lead to new therapeutic approaches targeting HIF1A in the development of TAMG.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1742-2094Test

الوصول الحر: https://doaj.org/article/22e3a343211b4a35a2bed8399f28723eTest

المؤلفون: Yan Zhao, Cheng Xing, Yating Deng, Can Ye, Hongling Peng

المصدر: Genes and Diseases, Vol 11, Iss 1, Pp 234-251 (2024)

مصطلحات موضوعية: Angiogenesis, Hematological malignancies, Hypoxia-inducible factor-1 alpha (HIF-1α), Immune escape, Targeted therapy, Medicine (General), R5-920, Genetics, QH426-470

الوصف: The hypoxic microenvironment is an essential characteristic of most malignant tumors. Notably, hypoxia-inducible factor-1 alpha (HIF-1α) is a key regulatory factor of cellular adaptation to hypoxia, and many critical pathways are correlated with the biological activity of organisms via HIF-1α. In the intra-tumoral hypoxic environment, HIF-1α is highly expressed and contributes to the malignant progression of tumors, which in turn results in a poor prognosis in patients. Recently, it has been indicated that HIF-1α involves in various critical processes of life events and tumor development via regulating the expression of HIF-1α target genes, such as cell proliferation and apoptosis, angiogenesis, glucose metabolism, immune response, therapeutic resistance, etc. Apart from solid tumors, accumulating evidence has revealed that HIF-1α is also closely associated with the development and progression of hematological malignancies, such as leukemia, lymphoma, and multiple myeloma. Targeted inhibition of HIF-1α can facilitate an increased sensitivity of patients with malignancies to relevant therapeutic agents. In the review, we elaborated on the basic structure and biological functions of HIF-1α and summarized their current role in various malignancies. It is expected that they will have future potential for targeted therapy.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2352304223001058Test; https://doaj.org/toc/2352-3042Test

الوصول الحر: https://doaj.org/article/300424bef78f417d810da6b82f0ac9b6Test

المؤلفون: Hasan Cagri Yildirim, Hicran Anik, Deniz Ates Ozdemir, Rashad Ismayilov, Arif Akyildiz, Kerim Cayiroz, Fahri Ceyhan, Oguzalp Kavruk, Deniz Can Guven, Ozturk Ates, Alp Usubutun, Zafer Arik

المصدر: Biomolecules & Biomedicine (2024)

مصطلحات موضوعية: Metastatic cervical cancer, squamous cell carcinoma (SCC), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 alpha (HIF-1 alpha), bevacizumab, Biology (General), QH301-705.5

الوصف: This study addresses the gap in understanding the prognostic relevance of hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression in metastatic cervical squamous cell carcinoma (SCC) patients undergoing anti-vascular endothelial growth factor-based therapy. A retrospective multicenter study (n = 34) explored HIF-1 alpha expression via immunohistochemistry in patients treated with platinum chemotherapy and bevacizumab. Median progression-free survival (PFS) was significantly lower in the HIF-1 alpha low score group compared to the high score group (4.9 vs 12.9 months, P = 0.014). Similarly, the median overall survival (OS) was significantly reduced in the HIF-1 alpha low score group (8.3 vs 20.4 months, P = 0.006). This study, the first of its kind, highlights the prognostic significance of HIF-1 alpha expression in metastatic cervical SCC patients treated with bevacizumab-based therapy.

وصف الملف: electronic resource

العلاقة: https://www.bjbms.org/ojs/index.php/bjbms/article/view/10255Test; https://doaj.org/toc/2831-0896Test; https://doaj.org/toc/2831-090XTest

الوصول الحر: https://doaj.org/article/0a6679b01dca4c8a82ddcef55b98579dTest

المؤلفون: Yang Hai, Ke Ren, Yarong Zhang, Lili Yang, Haoshi Cao, Xianxia Yuan, Linling Su, Hailong Li, Xiaoli Feng, Dongling Liu

المصدر: Biomedicine & Pharmacotherapy, Vol 171, Iss , Pp 116158- (2024)

مصطلحات موضوعية: Alzheimer's disease, Type 2 diabetes, Hypoxia, Hypoxia-inducible factor-1 alpha, Therapeutics. Pharmacology, RM1-950

الوصف: Alzheimer's disease (AD)-related brain deterioration is linked to the type 2 diabetes mellitus (T2DM) features hyperglycemia, hyperinsulinemia, and insulin resistance. Hypoxia as a common risk factor for both AD and T2DM. Hypoxia-inducible factor-1 alpha (HIF-1α) acts as the main regulator of the hypoxia response and may be a key target in the comorbidity of AD and T2DM. HIF-1α expression is closely related to hyperglycemia, insulin resistance, and inflammation. Tissue oxygen consumption disrupts HIF-1α homeostasis, leading to increased reactive oxygen species levels and the inhibition of insulin receptor pathway activity, causing neuroinflammation, insulin resistance, abnormal Aβ deposition, and tau hyperphosphorylation. HIF-1α activation also leads to the deposition of Aβ by promoting the abnormal shearing of amyloid precursor protein and inhibiting the degradation of Aβ, and it promotes tau hyperphosphorylation by activating oxidative stress and the activation of astrocytes, which further exasperates AD. Therefore, we believe that HIF-α has great potential as a target for the treatment of AD. Importantly, the intracellular homeostasis of HIF-1α is a more crucial factor than its expression level.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S0753332224000398Test; https://doaj.org/toc/0753-3322Test

الوصول الحر: https://doaj.org/article/c9cc72c664904ee4b5452983a8cb9fc3Test

المؤلفون: Hyytiainen, Aini, Mroueh, Rayan, Peltonen, Johanna, Wennerstrand, Pia, Mäkitie, Antti, Al-Samadi, Ahmed, Ventelä, Sami, Salo, Tuula

المساهمون: Research Programs Unit, Department of Oral and Maxillofacial Diseases, TRIMM - Translational Immunology Research Program, HUS Head and Neck Center, Clinicum, Korva-, nenä- ja kurkkutautien klinikka, Research Program in Systems Oncology, HUSLAB

مصطلحات موضوعية: Oral cancer, Chemoresistance, High-endothelial venules, Hypoxia-inducible factor-1 alpha, Octamer-binding transcription factor 4, Prognostic marker, Radioresistance, 3111 Biomedicine, 11832 Microbiology and virology

الوصف: Treatment of oral tongue squamous cell carcinoma (OTSCC) frequently includes surgery with postoperative radiotherapy (RT) or chemoradiotherapy (CRT). Resistance to RT or CRT remains a major clinical challenge and highlights the need to identify predictive markers for it. We included 71 OTSCC patients treated with surgery combined with RT or CRT. We evaluated the association between tumor budding, tumor-stroma ratio (TSR), depth of invasion (DOI), tumor-infiltrating lymphocytes (TILs), hypoxia-inducible factor-1alpha (HIF-1alpha) expression, octamer-binding transcription factor 4 (OCT4) expression, high-endothelial venules (HEVs), and disease-free survival (DFS) using uni- and multivariate analyses. No significant association was observed between the different histological and molecular markers (TSR, DOI, TILs, HEV, HIF-1alph, OCT4) and DFS. However, an associative trend between DOI, budding, and DFS was noted. Further studies with larger cohorts are needed to explore the prognostic value of DOI and budding for OTSCC patients treated with postoperative RT or CRT. ; Peer reviewed

وصف الملف: application/pdf

العلاقة: Hyytiainen , A , Mroueh , R , Peltonen , J , Wennerstrand , P , Mäkitie , A , Al-Samadi , A , Ventelä , S & Salo , T 2023 , ' Prognostic histological markers in oral tongue squamous cell carcinoma patients treated with (chemo)radiotherapy ' , APMIS , vol. 131 , no. 4 , pp. 142-151 . https://doi.org/10.1111/apm.13298Test; ORCID: /0000-0001-6039-0088/work/131540867; a0558ff9-f59a-46c2-90da-026a1322226e; http://hdl.handle.net/10138/570154Test; 000930530300001

الإتاحة: http://hdl.handle.net/10138/570154Test

المؤلفون: Yildirim, Hasan Cagri, Anik, Hicran, Ozdemir, Deniz Ates, Ismayilov, Rashad, Akyildiz, Arif, Cayiroz, Kerim, Ceyhan, Fahri, Kavruk, Oguzalp, Guven, Deniz Can, Ates, Ozturk, Usubutun, Alp, Arik, Zafer

المصدر: Biomolecules and Biomedicine; Advanced online ; 2831-090X ; 2831-0896

مصطلحات موضوعية: Metastatic cervical cancer, squamous cell carcinoma (SCC), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 alpha (HIF-1 alpha), bevacizumab

الوصف: This study addresses the gap in understanding the prognostic relevance of hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression in metastatic cervical squamous cell carcinoma (SCC) patients undergoing anti-vascular endothelial growth factor (VEGF)-based therapy. A retrospective multicenter study (n = 34) explored HIF-1 alpha expression via immunohistochemistry in patients treated with platinum chemotherapy and bevacizumab. Median progression-free survival (PFS) was significantly lower in the HIF-1 alpha low score group compared to the high score group (4.9 vs 12.9 months, P = 0.014). Similarly, the median overall survival (OS) was significantly reduced in the HIF-1 alpha low score group (8.3 vs 20.4 months, P = 0.006). This study, the first of its kind, highlights the prognostic significance of HIF-1 alpha expression in metastatic cervical SCC patients treated with bevacizumab-based therapy.

وصف الملف: application/pdf

العلاقة: https://www.bjbms.org/ojs/index.php/bjbms/article/view/10255/3202Test; https://www.bjbms.org/ojs/index.php/bjbms/article/view/10255Test

الإتاحة: https://doi.org/10.17305/bb.2024.10255Test
https://www.bjbms.org/ojs/index.php/bjbms/article/view/10255Test

المؤلفون: Jennifer M. Noto, M. Blanca Piazuelo, Judith Romero-Gallo, Alberto G. Delgado, Giovanni Suarez, Konstantina Akritidou, Miguel Girod Hoffman, Juan Carlos Roa, Cormac T. Taylor, Richard M. Peek

المصدر: Gut Microbes, Vol 15, Iss 2 (2023)

مصطلحات موضوعية: Helicobacter pylori, gastric inflammation, gastric cancer, hypoxia-inducible factor-1 alpha (HIF-1α), dimethyloxalylglycine (DMOG), prolyl hydroxylase (PHD), Diseases of the digestive system. Gastroenterology, RC799-869

الوصف: ABSTRACTHelicobacter pylori-induced inflammation is the strongest known risk factor for gastric adenocarcinoma. Hypoxia-inducible factor-1 (HIF-1α) is a key transcriptional regulator of immunity and carcinogenesis. To examine the role of this mediator within the context of H. pylori-induced injury, we first demonstrated that HIF-1α levels were significantly increased in parallel with the severity of gastric lesions in humans. In interventional studies targeting HIF-1α, H. pylori-infected mice were treated ± dimethyloxalylglycine (DMOG), a prolyl hydroxylase inhibitor that stabilizes HIF-1α. H. pylori significantly increased proinflammatory chemokines/cytokines and inflammation in vehicle-treated mice; however, this was significantly attenuated in DMOG-treated mice. DMOG treatment also significantly decreased function of the H. pylori type IV secretion system (T4SS) in vivo and significantly reduced T4SS-mediated NF-κB activation and IL-8 induction in vitro. These results suggest that prolyl hydroxylase inhibition protects against H. pylori-mediated pathologic responses, and is mediated, in part, via attenuation of H. pylori cag-mediated virulence and suppression of host proinflammatory responses.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1949-0976Test; https://doaj.org/toc/1949-0984Test

الوصول الحر: https://doaj.org/article/5ca1554c76e54c8382886b3806ff21b3Test

المؤلفون: Jirong Yan, Zhichao Xi, Jiaying Guo, Lin Xu, Xueyang Sun, Wanjing Sha, Milin Liu, Shenyu Zhao, Enrui Dai, Yu Xu, Hongxi Xu, Huiyan Qu

المصدر: Chinese Medicine, Vol 18, Iss 1, Pp 1-14 (2023)

مصطلحات موضوعية: Ventricular remodeling, Intestinal barrier integrity, LuQi Formula, Tight junction proteins, Hypoxia inducible factor-1 alpha, Other systems of medicine, RZ201-999

الوصف: Abstract Background Ventricular remodeling is the adaptive process in which the heart undergoes changes due to stress, leading to heart failure (HF). The progressive decline in cardiac function is considered to contribute to intestinal barrier impairment. LuQi Formula (LQF) is a traditional Chinese medicine preparation widely used in the treatment of ventricular remodeling and HF. However, the role of LQF in the impairment of intestinal barrier function induced by ventricular remodeling remains unclear. Materials and methods Ventricular remodeling was induced in rats by permanently ligating the left anterior descending branch coronary artery, and cardiac function indexes were assessed using echocardiography. Heart and colon tissue morphology were observed by hematoxylin–eosin, Masson’s trichrome and Alcian Blue Periodic acid Schiff staining. Myocardial cell apoptosis was detected using TUNEL and immunohistochemistry. Circulatory levels of brain natriuretic peptide (BNP), intestinal permeability markers endotoxin, D-lactate and zonulin, as well as inflammatory cytokines tumor necrosis factor alpha and interleukin-1 beta were measured by Enzyme-linked immunosorbent assay. Expression levels of tight junction (TJ) proteins and hypoxia-inducible factor-1 alpha (HIF-1α) in colon tissue were detected by immunofluorescence, immunohistochemistry and western blotting. Cardiac function indexes and intestinal permeability markers of patients with HF were analyzed before and after 2–4 months of LQF treatment. Results LQF protected cardiac function and alleviated myocardial fibrosis and apoptosis in rats with ventricular remodeling. LQF protected the intestinal barrier integrity in ventricular remodeling rats, including maintaining colonic tissue morphology, preserving the number of goblet cells and normal expression of TJ proteins. Furthermore, LQF upregulated the expression of HIF-1α protein in colon tissue. Intervention with a HIF-1α inhibitor weakened the protective effect of LQF on intestinal barrier integrity. Moreover, a reduction of HIF-1α aggravated ventricular remodeling, which could be alleviated by LQF. Correspondingly, the circulating levels of intestinal permeability markers and BNP in HF patients were significantly decreased, and cardiac function markedly improved following LQF treatment. Conclusions We demonstrated that LQF effectively protected cardiac function by preserving intestinal barrier integrity caused by ventricular remodeling, at least partially through upregulating HIF-1α expression.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1749-8546Test

الوصول الحر: https://doaj.org/article/e83f2ec17e4f4da18d88e1cc18c3383fTest

المؤلفون: Hao YIN, Ze ZHANG, Liu WU, Yingzhu WANG, Yuxin ZHENG, Xiaoting JIN

المصدر: 环境与职业医学, Vol 40, Iss 5, Pp 491-499 (2023)

مصطلحات موضوعية: diesel particulate matter, benzo[a]pyrene, ischemia-hypoxia injury, hypoxia-inducible factor-1 alpha, oxygen sensor, anaerobic metabolism, Medicine (General), R5-920, Toxicology. Poisons, RA1190-1270

الوصف: BackgroundThe exposure to diesel particulate matter (DPM) and its polycyclic aromatic hydrocarbons (PAH) is closely related to the morbidity and mortality of ischemic heart disease (IHD). However, it is unclear what key components and targets of DPM exposure involve in myocardial ischemia-hypoxia injury and associated mechanisms.ObjectiveTo identify key PAH components of DPM that act on myocardial hypoxic injury, andclarify the role of oxygen sensors-regulated anaerobic metabolism in DPM and key components-induced hypoxic injury and the targets of the key PAH components.MethodsHuman cardiomyocyte cell line AC16 cells were exposed to 0, 1, 5, and 10 μg·mL−1 DPM in a high glucose DMEM medium with 10% fetal bovine serum (FBS) (HGM) or low FBS (0.5%) in high glucose DMEM medium (LFM), for 12 h under 2% O2, and expression of hypoxia-inducible factor-1α (HIF-1α), Bax, and Cleaved-caspase3 was determined by Western blotting. Under normal condition, the cell viability was detected after PAH exposure for 12 h. Under the condition of ischemia-hypoxia model, cells were exposed to 0, 0.005, 0.5, and 5 µg·mL−1 PAH for 12 h, and the protein expression of HIF-1α, Bax, and Cleaved-caspase3 was determined. After exposure to DPM or PAH for 12 h, the contents of pyruvate and lactate in cells were detected. Pretreatment with glycolysis inhibitor GSK2837808A was used to explore the role of glycolysis in DPM and benzo[a]pyrene (BaP)-induced hypoxia injury. A molecular docking technique was used to analyze the binding affinity between PAH and oxygen sensors (prolyl hydroxylase domain-containing protein 2, PHD2, and factor-inhibiting hypoxia-inducible factor 1, FIH1), and the protein levels of PHD2, FIH1, and hydroxyl-HIF-1-alpha (OH-HIF-1α) after the DPM or BaP treatment were further determined.ResultsUnder hypoxia, DPM exposure in the LFM induced the expression of HIF-1α, Bax, and Cleaved-caspase3 (P0.05), other PAH decreased cell viability when the concentration was above 1 μg·mL−1 (P

وصف الملف: electronic resource

العلاقة: http://www.jeom.org/article/cn/10.11836/JEOM22416Test; https://doaj.org/toc/2095-9982Test

الوصول الحر: https://doaj.org/article/79d8eb0f4cb147bd97f49b3f4145affbTest

المؤلفون: Reem A. Qannita, Ayah I. Alalami, Amani A. Harb, Shereen M. Aleidi, Jalal Taneera, Eman Abu-Gharbieh, Waseem El-Huneidi, Mohamed A. Saleh, Karem H. Alzoubi, Mohammad H. Semreen, Mohammad Hudaib, Yasser Bustanji

المصدر: Pharmaceuticals, Vol 17, Iss 2, p 195 (2024)

مصطلحات موضوعية: hypoxia-inducible factor-1, hypoxia, cancer, HIF-1α, metabolism reprogramming, HIF-1 inhibitors, Medicine, Pharmacy and materia medica, RS1-441

الوصف: Hypoxia-inducible factor-1 (HIF-1) is a key regulator for balancing oxygen in the cells. It is a transcription factor that regulates the expression of target genes involved in oxygen homeostasis in response to hypoxia. Recently, research has demonstrated the multiple roles of HIF-1 in the pathophysiology of various diseases, including cancer. It is a crucial mediator of the hypoxic response and regulator of oxygen metabolism, thus contributing to tumor development and progression. Studies showed that the expression of the HIF-1α subunit is significantly upregulated in cancer cells and promotes tumor survival by multiple mechanisms. In addition, HIF-1 has potential contributing roles in cancer progression, including cell division, survival, proliferation, angiogenesis, and metastasis. Moreover, HIF-1 has a role in regulating cellular metabolic pathways, particularly the anaerobic metabolism of glucose. Given its significant and potential roles in cancer development and progression, it has been an intriguing therapeutic target for cancer research. Several compounds targeting HIF-1-associated processes are now being used to treat different types of cancer. This review outlines emerging therapeutic strategies that target HIF-1 as well as the relevance and regulation of the HIF-1 pathways in cancer. Moreover, it addresses the employment of nanotechnology in developing these promising strategies.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1424-8247/17/2/195Test; https://doaj.org/toc/1424-8247Test

الوصول الحر: https://doaj.org/article/c148d767dd004ccc9ba58d0ff874ab34Test