Targeted downregulation of HIF-1α for restraining circulating tumor microemboli mediated metastasis

Du, Junjie; Chen, Yijun; Zhong, Lingyu; Liu, Xuwentai; Xue, Lingjing; Zhang, Ying; Li, Yanyi; Li, Xiaoyü; Tang, Chao; Su, Zhigui; Zhang, Can

doi:10.1016/j.jconrel.2022.01.051

Cited by 12 publications

(10 citation statements)

References 35 publications

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“…Next, we isolated neutrophils from mouse bone marrow 33 , 34 , 38 , 39 , and purified by density gradient centrifugation. The isolated neutrophils showed a purity of 93% labeled by dual-positive of CD11b and Ly6G, the typical biomarkers of neutrophils ( Fig.…”

Section: Resultssupporting

confidence: 91%

Reprogrammed siTNFα/neutrophil cytopharmaceuticals targeting inflamed joints for rheumatoid arthritis therapy

Chen

Jiao²,

Huang³

et al. 2023

Acta Pharmaceutica Sinica B

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Section: Resultssupporting

confidence: 91%

Reprogrammed siTNFα/neutrophil cytopharmaceuticals targeting inflamed joints for rheumatoid arthritis therapy

Chen

Jiao²,

Huang³

et al. 2023

Acta Pharmaceutica Sinica B

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“…The group treated with Experimental Microspheres showed higher HIF-1α positive expression, revealing higher protein expression in the cytoplasm and nucleus. Hypoxia is one of the main effects of microsphere embolization, and it can induce the expression and activity of a transcription factor called HIF-1α in cells [ 34 ]. HIF-1 is a factor that has been widely studied, and it is one of the most common transcription factors in hypoxia [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

Highly tough and elastic microspheric gel for transarterial catheter embolization in treatment of liver metastasis tumor

Wang

Wan

et al. 2023

Regenerative Biomaterials

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Transarterial embolization is a widely recognized clinical treatment method for liver tumors. Given that the soft and easily damaged features of embolic particles may limit tumor embolization efficiency, the present study carries out an attempt of fabricating tough and elastic microspheric gel for promoting embolization efficiency. To promote the toughness of hydrogel, poly(ethylene glycol)-co-poly(ε-caprolactone)-co-poly(ethylene glycol) (PPP) and PPP with two terminal double bonds (PPPDA) are co-assembled into nano-micelles, which are connected with methacrylated chitosan (CSMA) to fabricate microspheric gels via microfluidic technology. Lowering double bond density of micelles promotes the freedom degree of micelles, significantly enhancing hydrogel toughness. To compensate for the strength loss caused by the decrease of double bond density of micelles, phytic acid (PA) are employed to interact with CS to form a physical network, further improving hydrogel strength and toughness. The CS-PPPDA&PPP-PA microspheric gels exhibit higher blocking effect in vitro. A rabbit VX2 liver metastasis tumor model is prepared to verify the embolization efficacy of CS-PPPDA&PPP-PA microspheric gels. Compared with clinical used microspheres, fewer CS-PPPDA&PPP-PA microspheric gels can achieve enough embolization efficiency. After embolization for 14 days, CS-PPPDA&PPP-PA microspheric gels exhibit improved tumor necrosis rate and promoted tumor cells apoptosis with reduced inflammation in surrounding tissues, confirming advanced embolic efficiency of tough microgels.

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“…L-mimosine (>98% purity; see Figure 1A ) was obtained from Sigma-Aldrich (St Louis, MO, USA) and dissolved in 50 mg/mL of 1 M NH 4 OH ( 31 ). BAY-87-2243 (a HIF1α-specific inhibitor; see Figure 1B ) was provided by Sigma-Aldrich (St Louis, MO, USA) and dissolved in 2 mg/mL of dimethyl sulfoxide ( 32 ). Fetal bovine serum (FBS), alpha modified Eagle’s medium (α-MEM), and Dulbecco’s modified Eagle’s medium (DMEM) were purchased from Gibco (Rockville, MD, USA).…”

Section: Methodsmentioning

confidence: 99%

Hypoxia-inducible factor 1α enhances RANKL-induced osteoclast differentiation by upregulating the MAPK pathway

Wang¹,

Liu²,

Qu³

et al. 2022

Ann Transl Med

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Background: Hypoxia (low-oxygen tension) and excessive osteoclast activation are common conditions in many bone loss diseases, such as osteoporosis, rheumatoid arthritis (RA), and pathologic fractures. Hypoxiainducible factor 1 alpha (HIF1α) regulates cellular responses to hypoxic conditions. However, it is not yet known how HIF1α directly affects osteoclast differentiation and activation. This study sought to. explore the effects of HIF1α on osteoclast differentiation and it's molecular mechanisms.Methods: L-mimosine, a prolyl hydroxylase (PHDs) domain inhibitor, was used to stabilize HIF1α in normoxia. In the presence of receptor activator of nuclear factor-kB (NF-kB) ligand (RANKL), RAW264.7 cells were cultured and stimulated by treatment with L-mimosine at several doses to maintain various levels of intracellular HIF1α. The multi-nucleated cells were assessed by a tartrate-resistant acid phosphatase (TRAP) and F-actin ring staining assays. The osteoclast-specific genes, such as Cathepsin K, β3-Integrin, TRAP, c-Fos, nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), and matrix metallo-proteinase 9 (MMP9), were analyzed by real time-polymerase chain reaction (RT-PCR). The expression of relevant proteins was analyzed by Western blot.Results: L-mimosine increased the content of intracellular HIF1α in a dose-dependent manner, which in turn promoted RANKL-induced osteoclast formation and relevant protein expression by upregulating the mitogen-activated protein kinase (MAPK) pathways.Conclusions: Our findings suggest that HIF1α directly increases the osteoclast differentiation of RANKLmediated RAW264.7 cells in vitro by upregulating the MAPK pathways.

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Targeted downregulation of HIF-1α for restraining circulating tumor microemboli mediated metastasis

Cited by 12 publications

References 35 publications

Reprogrammed siTNFα/neutrophil cytopharmaceuticals targeting inflamed joints for rheumatoid arthritis therapy

Reprogrammed siTNFα/neutrophil cytopharmaceuticals targeting inflamed joints for rheumatoid arthritis therapy

Highly tough and elastic microspheric gel for transarterial catheter embolization in treatment of liver metastasis tumor

Hypoxia-inducible factor 1α enhances RANKL-induced osteoclast differentiation by upregulating the MAPK pathway

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