Glycogen synthase kinase-3β (GSK-3β), a serine/threonine protein kinase, has been reported to show essential roles in molecular pathophysiology of many diseases. Mitochondrion is a dynamic organelle for producing cellular energy and determining cell fates. Stress-induced translocated GSK-3β may interact with mitochondrial proteins, including PI3K-Akt, PGC-1α, HK II, PKCε, components of respiratory chain, and subunits of mPTP. Mitochondrial pool of GSK-3β has been implicated in mediation of mitochondrial functions. GSK-3β exhibits the regulatory effects on mitochondrial biogenesis, mitochondrial bioenergetics, mitochondrial permeability, mitochondrial motility, and mitochondrial apoptosis. The versatile functions of GSK-3β might be associated with its wide range of substrates. Accumulative evidence demonstrates that GSK-3β inactivation may be potentially developed as the promising strategy in management of many diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Intensive efforts have been made for exploring GSK-3β inhibitors. Natural products provide us a great source for screening new lead compounds in inactivation of GSK-3β. The key roles of GSK-3β in mediation of mitochondrial functions are discussed in this review.

Cancer cells are usually exposed to stressful environments, such as hypoxia, nutrient deprivation, and other metabolic dysfunctional regulation, leading to continuous endoplasmic reticulum (ER) stress. As the most conserved branch among the three un-folded protein response (UPR) pathways, Inositol-requiring enzyme 1α (IRE1α)-X-box-binding protein 1 (XBP1) signaling has been implicated in cancer development and progression. Active XBP1 with transactivation domain functions as a transcription factor to regulate the expression of downstream target genes, including many oncogenic factors. The regulatory activity of XBP1 in cell proliferation, apoptosis, metastasis, and drug resistance promotes cell survival, leading to tumorigenesis and tumor progression. In addition, the XBP1 peptides-based vaccination and/or combination with immune-modulatory drug administration have been developed for effective management for several cancers. Potentially, XBP1 is the biomarker of cancer development and progression and the strategy for clinical cancer management.

Kaempferol has been reported to exhibit beneficial effect on the osteogenic differentiation in mesenchymal stem cells (MSC) and osteoblasts. In our previous study, dexamethasone (DEX) demonstrated inhibitory effect on MC3T3-E1 cells differentiation. In this study, we mainly explored the protective effect of kaempferol on the inhibitory activity of DEX in the osteogenesis of MC3T3-E1 cells. We found that kaempferol ameliorated the proliferation inhibition, cell cycle arrest, and cell apoptosis and increased the activity of alkaline phosphatase (ALP) and the mineralization in DEX-treated MC3T3-E1 cells. Kaempferol also significantly enhanced the expression of osterix (Osx) and runt-related transcription factor 2 (Runx2) in MC3T3-E1 cells treated with DEX. In addition, kaempferol attenuated DEX-induced reduction of cyclin D1 and Bcl-2 expression and elevation of p53 and Bax expression. Kaempferol also activated JNK and p38-MAPK pathways in DEX-treated MC3T3-E1 cells. Furthermore, kaempferol improved bone mineralization in DEX-induced bone damage in a zebrafish larvae model. These data suggested that kaempferol ameliorated the inhibitory activity of DEX in the osteogenesis of MC3T3-E1 cells by activating JNK and p38-MAPK signaling pathways. Kaempferol exhibited great potentials in developing new drugs for treating glucocorticoid-induced osteoporosis.

Objective. Critical limb ischemia (CLI) is the most dangerous stage of peripheral artery disease (PAD). Many basic researches and clinical treatment had been focused on stem cell transplantation for CLI. This systematic review was performed to review evidence for safety and efficacy of autologous stem cell therapy in CLI. Methods. A systematic literature search was performed in the SinoMed, PubMed, Embase, ClinicalTrials.gov, and Cochrane Controlled Trials Register databases from building database to January 2018. Results. Meta-analysis showed that cell therapy significantly increased the probability of ulcer healing (RR = 1.73, 95% CI = 1.45–2.06), angiogenesis (RR = 5.91, 95% CI = 2.49–14.02), and reduced the amputation rates (RR = 0.59, 95% CI = 0.46–0.76). Ankle-brachial index (ABI) (MD = 0.13, 95% CI = 0.11–0.15), TcO₂ (MD = 12.22, 95% CI = 5.03–19.41), and pain-free walking distance (MD = 144.84, 95% CI = 53.03–236.66) were significantly better in the cell therapy group than in the control group (P<0.01). Conclusions. The results of this meta-analysis indicate that autologous stem cell therapy is safe and effective in CLI. However, higher quality and larger RCTs are required for further investigation to support clinical application of stem cell transplantation.

Glucocorticoid (GC) therapy is the leading cause of secondary osteoporosis and the therapeutic and preventative drugs for GC-induced osteoporosis are limited. In this study, we investigated the protective effects of geniposide on dexamethasone (DEX)-induced osteogenic inhibition in MC3T3-E1 cells. The results showed that there was no obvious toxicity on MC3T3-E1 cells when geniposide was used at the doses ranging from 1 to 75 μM. In DEX-treated MC3T3-E1 cells, geniposide promoted the alkaline phosphatase (ALP) activity and the mineralization. In addition, geniposide also significantly increased the mRNA and protein expression of osteopontin (OPN), Runt-related transcription factor 2 (Runx2), and Osterix (Osx) in DEX-treated MC3T3-E1 cells. Furthermore, geniposide activated ERK pathway in DEX-treated MC3T3-E1 cells. The ERK activation inhibitor U0126 and glucagon-like peptide-1 (GLP-1) receptor antagonist exendin 9-39 abolished the geniposide-induced activation of ERK and inhibited the protective effect of geniposide. Taken together, our study revealed that geniposide alleviated GC-induced osteogenic suppression in MC3T3-E1 cells. The effect of geniposide was at least partially associated with activating ERK signaling pathway via GLP-1 receptor. Geniposide might be a potential therapeutic agent for GC-induced osteoporosis.