BNIP3 in hypoxia-induced mitophagy: Novel insights and promising target for non-alcoholic fatty liver disease.

BNIP3 localizes to the outer mitochondrial membrane, has been demonstrated to be extensively involved in abnormalities to mitochondrial metabolic function and dynamicsand in non-alcoholic fatty liver disease (NAFLD). However, its role in NAFLD under hypoxia remains unclear. This study aimed to investigate the expression and the role of BNIP3 in NAFLD under hypoxia, and explore its involvement in regulating NAFLD mitophagy, fatty acid β-oxidation both in vivo and in vitro.

Expression of protein phosphatase 4 in different tissues under hypoxia.

Relevant research data shows that there is a certain degree of energy metabolism imbalance in highland residents. Protein phosphatase 4 (PP4) has been found as a new factor in the regulation of sugar and lipid metabolism. Here, we investigate the differential expression of PP4 at a simulated altitude of 4,500 m in the heart, lung, and brain tissues of rats.

protoscoleces enhance glycolysis to promote M2 Macrophages through PI3K/Akt/mTOR Signaling Pathway.

Alveolar Echinococcosis (AE) is a zoonotic parasitic disease caused by , but its pathogenesis remains unclear. The primary objective of this study is to explore whether protoscoleces (PSCs) regulate macrophage polarization and glucose metabolism by PI3K/Akt/mTOR signaling pathway. We found that large numbers of CD68 macrophages gathered in close liver issue from the lesion in AE patients.

Cepharanthine hydrochloride inhibits the Wnt/β‑catenin/Hedgehog signaling axis in liver cancer.

Cepharanthine, a biscoclaurine alkaloid isolated from the roots of Hayata, has been reported to demonstrate antitumor activity across multiple cancer types; however, the mechanisms are still under investigation. High transcriptional responses by both the Hedgehog and Wnt pathways are frequently associated with specific human cancers, including liver cancer. To investigate whether these signaling pathways are involved in the pharmaceutical action of cepharanthine, we investigated Hedgehog and Wnt signaling in models of liver cancer treated with a semi‑synthetic cepharanthine derivative, cepharanthine hydrochloride (CH), and .

The effects of hypoxia on mitochondrial function and metabolism in gastric cancer cells.

Background: A number of studies have found that metabolic disorders are the characteristic manifestations of tumor cells. However, the effects of hypoxic environment on mitochondrial function and glucose metabolism of tumor cells were still unclear. The study wanted to explore the regulatory mechanism of hypoxic environment on mitochondrial function and metabolism in gastric cancer cells.

Lactate Modulates Cellular Metabolism Through Histone Lactylation-Mediated Gene Expression in Non-Small Cell Lung Cancer.

Lactate has been observed to fuel TCA cycle and is associated with cancer progression in human lung cancer, the leading cause of cancer deaths worldwide, but the effect of lactate on lung cancer metabolism is rarely reported. In this study, disordered metabolism in non-small cell lung cancer was demonstrated by increased G6PD and SDHA protein levels immunofluorescence, and up-regulated lactate dehydrogenase was found to be associated with poor prognosis. Then flow cytometry and Seahorse XFe analyzer were utilized to detect the effect of lactate on glycolysis and mitochondrial function in non-small cell lung cancer cells.

High-concentration homocysteine inhibits mitochondrial respiration function and production of reactive oxygen species in neuron cells.

Objective: Homocysteine plays critical roles in cellular redox homeostasis, and hyperhomocysteinemia has been associated with multiple diseases, including neurological disorders involving reactive oxygen species-inducing and pro-inflammatory effects of homocysteine that are related to mitochondria. This study investigated the role of homocysteine in regulating mitochondria of neuron cell lines.

Methods: Neuron cells were pre-treated with homocysteine, and then flow cytometry was used to detect reactive oxygen species production and mitochondrial membrane potential, while Seahorse XFp Mito stress assay was used to comprehensively analyze mitochondrial function.

The critical role of dysregulated Hh-FOXM1-TPX2 signaling in human hepatocellular carcinoma cell proliferation.

Background: Aberrant activation of the Hedgehog (Hh) signaling pathway is frequently observed in hepatocellular carcinoma (HCC), nevertheless, the precise molecular mechanism remains unclear. Forkhead box M1 (FOXM1), a target of the Hh pathway, is a key oncofetal transcription factor and a master cell cycle regulator. Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is an oncogene critical for mitosis.

GLI2 promotes cell proliferation and migration through transcriptional activation of ARHGEF16 in human glioma cells.

Background: The Hedgehog (Hh) signaling pathway plays critical roles in modulating embryogenesis and maintaining tissue homeostasis, with glioma-associated oncogene (GLI) transcription factors being the main mediators. Aberrant activation of this pathway is associated with various human malignancies including glioblastoma, although the mechanistic details are not well understood.

Methods: We performed a microarray analysis of genes that are differentially expressed in glioblastoma U87 cells overexpressing GLI2A, the active form of GLI2, relative to the control cells.

Molecular mechanisms of suppressor of fused in regulating the hedgehog signalling pathway.

Highly conserved throughout evolution, the hedgehog (Hh) signalling pathway has been demonstrated to be involved in embryonic development, stem cell maintenance and tissue homeostasis in animals ranging from invertebrates to vertebrates. In the human body, a variety of cancer types are associated with the aberrantly activated Hh signalling pathway. Multiple studies have revealed suppressor of fused (Sufu) as a key negative regulator of this signalling pathway.

Nek2A/SuFu feedback loop regulates Gli-mediated Hedgehog signaling pathway.

Suppressor of Fused (SuFu), one of the most conserved components of the Hedgehog (Hh) signaling, binds Gli transcription factors and impedes activation of target gene expression in mammalian cells. Despite the central importance of SuFu in the Hh pathway, little is known about SuFu regulation. In a previous study, we identified NIMA-related expressed kinase 2A (Nek2A) as a SuFu-interacting protein.

Aberrantly activated Gli2-KIF20A axis is crucial for growth of hepatocellular carcinoma and predicts poor prognosis.

Unlabelled: Glioma-associated oncogene 2 (Gli2), a primary transcriptional regulator of Hedgehog (Hh) signaling, is essential for hepatocellular carcinoma (HCC) growth and survival. However, the underlying molecular mechanism and crucial downstream targets of Gli2 in human HCC are not fully understood. Here, we report the identification of kinesin family member 20A (KIF20A) as a novel downstream target of Gli2, which is important for HCC proliferation and tumor growth.

Down-regulation of Gli transcription factor leads to the inhibition of migration and invasion of ovarian cancer cells via integrin β4-mediated FAK signaling.

Background: Recent evidence suggests that aberrant activation of Hedgehog (Hh) signaling by Gli transcription factors is characteristic of a variety of aggressive human carcinomas including ovarian cancer. Therefore, chemotherapeutic agents that inhibit activation of Gli transcription factors have emerged as promising novel therapeutic drugs for ovarian cancer.

Results: In this study, we show that activation of Hh signaling promoted cellular migration and invasion, whereas blockade of Hh signaling with GANT61 suppressed cellular migration and invasion in ovarian cancer cells.

Suppression of growth and migration by blocking the Hedgehog signaling pathway in gastric cancer cells.

Purpose: Previous studies have indicated that Hedgehog signaling is essential for gastric cancer development, but its precise role is still unclear. The aim of this study was to clarify the role of Hedgehog signaling in gastric cancer development.

Methods: The expression of key Hedgehog signaling components in clinical samples of sequential gastric cancer stages was assessed by immunohistochemistry.