HIF-1a

Human Papillomaviruses have been associated with the occurrence of cervical cancer, the fourth most common cancer that affects women globally, while 70% of cases are caused by infection with the high-risk types HPV16 and HPV18. The integration of these viruses' oncogenes E6 and E7 into the host's genome affects a multitude of cellular functions and alters the expression of molecules. The aim of this study was to investigate how these oncogenes contribute to the expression of immune system control molecules, using cell lines with integrated HPV16 genome, before and after knocking out E6 viral gene using the CRISPR/Cas9 system, delivered with a lentiviral vector...

Novel components of the mitochondrial fission machinery, mitochondrial dynamics proteins of 49 kDa (MiD49) and 51 kDa (MiD51), have been recently described, and their potential therapeutic targets for treating cardiovascular disease have been shown, including acute myocardial infarction (AMI), anthracycline cardiomyopathy and pulmonary arterial hypertension (PAH). Here, we examined the role of MiD49 and MiD51 in atherosclerosis. MiD49/51 expression was increased in the aortic valve endothelial cells (ECs) of high-fat diet-induced atherosclerosis in ApoE-/- mice and IL-8-induced human umbilical vein endothelial cells (HUVECs), which accelerated dynamin-related protein 1 (Drp1)-mediated mitochondrial fission...

BACKGROUND: Vitexicarpin (VIT), an isoflavone derived from various medicinal herbs, has shown promising anti-tumor activities against multiple cancer cells. However, the understanding of the mechanisms and potential targets of VIT in treating triple-negative breast cancer (TNBC) remains limited. METHODS: The potential VIT targets were searched for in the Super-PRED online database, while the TNBC targets were acquired in the DisGeNET database, and the Veeny database was used to identify the VIT and TNBC targets that overlapped...

Hypoxia inducible factor-1(HIF-1), a heterodimeric transcription factor, is composed of two subunits (HIF-1α and HIF-1β). It is considered as an important transcription factor for regulating oxygen changes in hypoxic environment, which can regulate the expression of various hypoxia-related target genes and play a role in acute and chronic hypoxia pulmonary vascular reactions. In this paper, the function and mechanism of HIF-1a expression and regulation in hypoxic pulmonary hypertension (HPH) were reviewed, and current candidate schemes for treating pulmonary hypertension by using HIF-1a as the target were introduced, so as to provide reference for studying the pathogenesis of HPH and screening effective treatment methods...

The molecular mechanisms induced by hypoxia are misunderstood in non-small cell lung cancer (NSCLC), and above all the hypoxia and RASSF1A/Hippo signaling relationship. We confirmed that human NSCLC (n = 45) as their brain metastases (BM) counterpart are hypoxic since positive with CAIX-antibody (target gene of Hypoxia-inducible factor (HIF)). A severe and prolonged hypoxia (0.2% O2, 48 h) activated YAP (but not TAZ) in Human Bronchial Epithelial Cells (HBEC) lines by downregulating RASSF1A/kinases Hippo (except for NDR2) regardless their promoter methylation status...

Glycolysis is the preferred energy metabolism pathway in cancer cells even when the oxygen content is sufficient. Through glycolysis, cancer cells convert glucose into pyruvic acid and then lactate to rapidly produce energy and promote cancer progression. Changes in glycolysis activity play a crucial role in the biosynthesis and energy requirements of cancer cells needed to maintain growth and metastasis. This review focuses on ovarian cancer and the significance of key rate-limiting enzymes (hexokinase, phosphofructokinase, and pyruvate kinase, related signaling pathways (PI3K-AKT, Wnt, MAPK, AMPK), transcription regulators (HIF-1a), and non-coding RNA in the glycolytic pathway...

Approximately 30% of glioma patients are able to survive beyond one year postdiagnosis. And this short time is often overshadowed by glioma-associated epilepsy. This condition severely impairs the patient's quality of life and causes great suffering. The genetic, molecular and cellular mechanisms underlying tumour development and epileptogenesis remain incompletely understood, leading to numerous unanswered questions. The various types of gliomas, namely glioblastoma, astrocytoma and oligodendroglioma, demonstrate distinct seizure susceptibility and disease progression patterns...

BACKGROUND: Bone morphogenetic protein 9 (BMP9) is a promising growth factor in bone tissue engineering, while the detailed molecular mechanism underlying BMP9-oriented osteogenesis remains unclear. In this study, we investigated the effect of lysyl oxidase (Lox) on the BMP9 osteogenic potential via in vivo and in vitro experiments, as well as the underlying mechanism. METHODS: PCR assay, western blot analysis, histochemical staining, and immunofluorescence assay were used to quantify the osteogenic markers level, as well as the possible mechanism...

Group 3 innate lymphoid cells (ILC3s) are vital for defending tissue barriers from invading pathogens. Hypoxia influences the production of intestinal ILC3-derived cytokines by activating HIF. Yet, the mechanisms governing HIF-1α in ILC3s and other innate RORγt+ cells during in vivo infections are poorly understood. In our study, transgenic mice with specific Hif-1a gene inactivation in innate RORγt+ cells (RAG1KO HIF-1α▵Rorc ) exhibit more severe colitis following Citrobacter rodentium infection, primarily due to the inability to upregulate IL-22...

Mounting evidence indicates the potential involvement of ATP-citrate lyase (ACLY) in the modulation of various cancer types. Nevertheless, the precise biological significance of ACLY in gastric cancer (GC) remains elusive. This study sought to elucidate the biological function of ACLY and uncover its influence on peritoneal metastasis in GC. The expression of ACLY was assessed using both real-time quantitative PCR and western blot techniques. To investigate the impact of ACLY on the proliferation of gastric cancer (GC) cells, colony formation and 5-ethynyl-2'-deoxyuridine (EdU) assays were performed...

The developmental fate of ovarian follicles is primarily determined by the survival status (proliferation or apoptosis) of granulosa cells (GCs). Owing to the avascular environment within follicles, GCs are believed to live in a hypoxic niche. Follicle-stimulating hormone (FSH) has been reported to improve GCs survival by governing hypoxia-inducible factor-1α (HIF-1α)-dependent hypoxia response, but the underlying mechanisms remain poorly understood. Growth arrest-specific gene 6 (GAS6) is a secreted ligand of tyrosine kinase receptors, and has been documented to facilitate tumor growth...

OBJECTIVE: Previous studies showed the PRP have the therapeutic effects for KOA, but the more detail roles remained unclear and therefore this study was carried on to explore the deeper mechanisms for PRP. METHODS: NRS and WOMAC scores were used to evaluate the clinical efficacy before surgery, 1 month and 6 months after surgery, and the postoperative joint structure changes (n = 24). Examination of pathology of the femoral condyle plate in rats using HE staining (n = 6); Angiogenesis experiments were used to investigate the effect of different groups of cell culture supernatants on the tubular structure formation capacity of HUVECs (n = 3)...

INTRODUCTION: Optic neuritis (ON) is often an early sign of multiple sclerosis (MS), and recent studies show a link between HIF-1 pathway activation and inflammation. This study aimed to determine if inhibition of the HIF-1 pathway using the HIF-1a antagonist acriflavine (ACF) can reduce clinical progression and rescue the ocular phenotype in an experimental autoimmune encephalomyelitis (EAE) ON model. METHODS: EAE-related ON was induced in 60 female C57BL/6J mice by immunization with MOG33-55, and 20 EAE mice received daily systemic injections of ACF at 5 mg/kg...

BACKGROUND: Ovarian cancer has been a worldwide health burden for women and its progression is highly hypoxia-independent. Here, we investigated the exact mechanisms by which hypoxia contributes to the malignant progression of ovarian cancer. METHOD: MTT, transwell, colony formation, and scratch wound healing assays were carried out for cellular functions. The underlying mechanism by which hypoxia functions was explored by RNA-seq, enrichment analysis, western blotting, qRT-PCR, flow cytometry, ChIP, luciferase reporter, and ELISA...

OBJECTIVE: To evaluate the effect of pharmacological modulation of HIF-1 on the expression of IL-33 and IL-17 in a murine model of allergic pulmonary inflam- mation (API) with different degrees of severity. METHODS: 5 mice/group received ovalbumin (OVA) 1(mild), 2(moderate) or 3(severe) challenges via i.t. prior to allergen sensitization, in addition to the HIF-1 induction or inhibition groups, received EDHB (OVA+EDHB) i.p. or 2ME (OVA+2ME) i.t. respectively. Control groups received saline solution (SS) in the same way...

Fabry disease (FD) is caused by α-galactosidase A (AGAL) enzyme deficiency, leading to globotriaosylceramide accumulation (Gb3) in several cell types. Pain is one of the pathophysiologically incompletely understood symptoms in FD patients. Previous data suggest an involvement of hypoxia and mitochondriopathy in FD pain development at dorsal root ganglion (DRG) level. Using immunofluorescence and quantitative real-time polymerase chain reaction (qRT PCR), we investigated patient-derived endothelial cells (EC) and DRG tissue of the GLA knockout (KO) mouse model of FD...

BACKGROUND: Spindle and kinetochore-associated complex subunit 3 (SKA3) plays an important role in cell proliferation by regulating the separation of chromosomes and their division into daughter cells. Previous studies demonstrated that SKA3 was strongly implicated in tumor development and progression. However, the roles of SKA3 in cholangiocarcinoma (CCA) and the underlying mechanisms remain unclear. METHODS: Next-generation sequencing (NGS) was performed with paired CCA tissues and normal adjacent tissues (NATs)...

PURPOSE: Stromal fibrosis limits nutritional supply and disarrays metabolism in pancreatic cancer (PDA, pancreatic ductal adenocarcinoma). Understanding of the molecular basis underlying metabolic cues would improve PDA management. The current study determined the interaction between glucose-regulated proteins 78 (GRP78) and hypoxia-inducible factor 1α (HIF-1α) and its mechanistic roles underlying PDA response to oxygen and glucose restrains. EXPERIMENTAL DESIGN: Gene expression and its association with clinicopathologic characteristics of patients with PDA and mouse models were analyzed using IHC...

OBJECTIVE: Bazhen Decoction (BZD) is a common adjuvant therapy drug for colorectal cancer (CRC), although its anti-tumor mechanism is unknown. This study aims to explore the core components, key targets, and potential mechanisms of BZD treatment for CRC. METHODS: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) was employed to acquire the BZD's active ingredient and targets. Meanwhile, the Drugbank, Therapeutic Target Database (TTD), DisGeNET, and GeneCards databases were used to retrieve pertinent targets for CRC...

Post-stroke depression (PSD) is a serious neuropsychiatric complication post stroke and leads to cognitive deficits. This study was conducted to explore the molecular mechanism of hypoxia-inducible factor-1α (HIF-1A) in cognitive dysfunction in rats with PSD. The rat model of PSD was established by middle cerebral artery occlusion, followed by 3 weeks of treatment with chronic unpredictable mild stress. The levels of miR-582-5p, HIF-1A, and neighbor of Brca1 gene (NBR1) in brain tissues were determined using RT-qPCR...