AMPKα2 Regulates Hypoxia-Inducible Factor-1α Stability and Neutrophil Survival to Promote Vascular Repair After Ischemia

Meng

Adv Healthcare Materials

et al. 2022

Various scaffolding systems have been attempted to facilitate vascularization in tissue engineering by optimizing biophysical properties (e.g., vascular-like structures, porous architectures, surface topographies) or loading biochemical factors (e.g., growth factors, hormones). However, vascularization during ossification remains an unmet challenge that hampers the repair of large bone defects. In this study, reconstructing vascularized bones in situ against critical-sized bone defects is endeavored using newly developed scaffolds made of chemically cross-linked gelatin microsphere aggregates (C-GMSs). The rationale of this design lies in the creation and optimization of cell-material interfaces to enhance focal adhesion, proliferation, and function of anchorage-dependent functional cells. In vitro trials are carried out by coculturing human aortic endothelial cells (HAECs) and murine osteoblast precursor cells (MC3T3-E1) within C-GMS scaffolds, in which endothelialized bone-like constructs are yielded. Angiogenesis and osteogenesis induced by C-GMSs scaffold are further confirmed via subcutaneous-embedding trials in nude mice. In situ trials for the repair of critical-sized femoral defects are subsequently performed in rats. The acellular C-GMSs with interconnected macropores, exhibit the capability to recruit the endogenous cells (e.g., bone-forming cells, vascular forming cells, immunocytes) and then promote vascularized bone regeneration as well as integration with host bone.

Section: Resultsmentioning

confidence: 99%

Biomaterial Scaffolds Made of Chemically Cross‐Linked Gelatin Microsphere Aggregates (C‐GMSs) Promote Vascularized Bone Regeneration

Meng

Adv Healthcare Materials

et al. 2022

“…Furthermore, Cui et al (2014) observed that aloin could reduce alanine transaminase and oxaloacetic transaminase activities in the serum of rats and the total cholesterol and triglyceride (TG) levels in serum; however, aloin did not affect the level of low‐density lipoprotein. AMPK‐α2 is a group of genes involved in lipid metabolism (Satoh, 2017). Aloin can inhibit the alcohol‐induced decrease in AMPK‐α2 expression, playing a protective role against alcohol‐induced steatosis in mice (Cui et al, 2014).…”

Section: Resultsmentioning

confidence: 99%

The potential health benefits of aloin from genus Aloe

Xiao

Chen

et al. 2022

Phytotherapy Research

The Aloe species is known for its medicinal and cosmetic properties. Aloin is an active ingredient found in the leaves of medicinal plants of the genus Aloe. Aloin has attracted considerable interest for its antiinflammatory, anticancer, antibacterial, and antioxidant activities. However, since its clinical application is restricted by its unclear mechanism of action, a deeper understanding of its pharmacological activity is required. This review provides an overview of current pharmacological and toxicological studies published in English from February 2000 to August 2021. Herein, we summarized the sources and potential health benefits of aloin from a clinical application perspective to guide for further studies on the sources of aloin, aimed at efficiently increasing aloin production. Importantly, the function and mechanism of action of aloin remain unclarified. In future research, it is necessary to develop new approaches for studying the pharmacological molecular mechanisms underlying the activity of this compound against various diseases.

“…Berberine may destabilize HIF-1α by increasing PTEN levels. In addition, AMPK is known to potentiate doxorubicin resistance in breast cancer [ 34 ], and HIF-1α can be stabilized by AMPKα2, one of the catalytic subunits of AMPK [ 35 ]. Therefore, berberine may sensitize cancer cells to doxorubicin by regulating the AMPKα2-HIF-1α axis ( Figure 1 and Table 1 ).…”

Section: Alkaloid and Organosulfur Compounds From Natural Sourcesmentioning

confidence: 99%

Anti-Cancer Activity of Phytochemicals Targeting Hypoxia-Inducible Factor-1 Alpha

Yun

Son

Choi

et al. 2021

IJMS

Hypoxia-inducible factor-1 alpha (HIF-1α) is overexpressed in cancer, leading to a poor prognosis in patients. Diverse cellular factors are able to regulate HIF-1α expression in hypoxia and even in non-hypoxic conditions, affecting its progression and malignant characteristics by regulating the expression of the HIF-1α target genes that are involved in cell survival, angiogenesis, metabolism, therapeutic resistance, et cetera. Numerous studies have exhibited the anti-cancer effect of HIF-1α inhibition itself and the augmentation of anti-cancer treatment efficacy by interfering with HIF-1α-mediated signaling. The anti-cancer effect of plant-derived phytochemicals has been evaluated, and they have been found to possess significant therapeutic potentials against numerous cancer types. A better understanding of phytochemicals is indispensable for establishing advanced strategies for cancer therapy. This article reviews the anti-cancer effect of phytochemicals in connection with HIF-1α regulation.