YAP/miR-524-5p axis negatively regulates TXNIP expression to promote chondrosarcoma cell growth.

Chondrosarcoma (CHS) is the second most common bone malignant tumor and currently has limited treatment options. We have recently demonstrated that thioredoxin interacting protein (TXNIP) plays a crucial role in the oncogenesis of bone sarcoma, yet its implication in CHS is underdetermined. In the present study, we first found that knockdown of TXNIP promotes the proliferation of CHS cell largely through increasing their glycolytic metabolism, which is well-known as Warburg effect for providing energy. Consistent with our previous report that YAP is fundamental for CHS cell growth, herein we revealed that YAP functioned as an upstream molecule of TXNIP, and that YAP negatively regulated TXNIP mRNA and protein expression both in vitro and in vivo. Mechanistically, although knockdown of YAP upregulated both the nuclear and cytoplasmic TXNIP expression, we did not observe any obvious interaction between YAP and TXNIP; instead, miRNA-524-5p was demonstrated to be required for YAP-regulated TXNIP expression and thus controlling CHS cell growth. Together, our study reveals that TXNIP is a tumor suppressor in terms of CHS, and that the YAP/miRNA-524-5p/TXNIP signaling axis may provide a novel clue for CHS targeted therapy.

Clinical effects of antidiabetic drugs on psoriasis: The perspective of evidence-based medicine.

Psoriasis and diabetes shared common underlying pathophysiological mechanisms. Emerging data suggested that antidiabetic medications may improve the psoriasis severity in patients with diabetes mellitus. Several hypoglycemic agents including thiazolidinediones, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and biguanides have been reported to make a remarkable reduction in the Psoriasis Area and Severity Index score from baseline. This antipsoriatic effect could be mediated not only by the glucose-lowering action of these agents but also via inhibition of keratinocyte over proliferation, increase expression of differentiation markers, suppression the immune inflammatory pathway, and blocking the calcium channels and mitogen-activated protein kinase signaling pathways. On the other hand, there was no significant increase in adverse reactions associated with the treatment of pioglitazone or metformin. However, previous studies often had the relatively short duration of the trials, and did not have enough power to assess recurrence of psoriasis. Potential bias in the study and missing data could undermine the reliability of the results. Therefore, the appropriately randomized controlled studies with large sample sizes and long-term durations in various psoriasis patients are warranted for further support.

Aldehyde dehydrogenase 2 preserves mitochondrial morphology and attenuates hypoxia/reoxygenation-induced cardiomyocyte injury.

BACKGROUND: Disturbance of mitochondrial fission and fusion (termed mitochondrial dynamics) is one of the leading causes of ischemia/reperfusion (I/R)-induced myocardial injury. Previous studies showed that mitochondrial aldehyde dehydrogenase 2 (ALDH2) conferred cardioprotective effect against myocardial I/R injury and suppressed I/R-induced excessive mitophagy in cardiomyocytes. However, whether ALDH2 participates in the regulation of mitochondrial dynamics during myocardial I/R injury remains unknown. METHODS: In the present study, we investigated the effect of ALDH2 on mitochondrial dynamics and the underlying mechanisms using the H9c2 cells exposed to hypoxia/reoxygenation (H/R) as an in vitro model of myocardial I/R injury. RESULTS: Cardiomyocyte apoptosis was significantly increased after oxygen-glucose deprivation and reoxygenation (OGD/R), and ALDH2 activation largely decreased the cardiomyocyte apoptosis. Additionally, we found that both ALDH2 activation and overexpression significantly inhibited the increased mitochondrial fission after OGD/R. Furthermore, we found that ALDH2 dominantly suppressed dynamin-related protein 1 (Drp1) phosphorylation (Ser616) and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation (Thr172) but not interfered with the expression levels of mitochondrial shaping proteins. CONCLUSIONS: We demonstrate the protective effect of ALDH2 against cardiomyocyte H/R injury with a novel mechanism on mitochondrial fission/fusion.

Protein-Based Three-Dimensional Whispering-Gallery-Mode Micro-Lasers with Stimulus-Responsiveness.

For the first time, proteins, a promising biocompatible and functionality-designable biomacromolecule material, acted as the host material to construct three-dimensional (3D) whispering-gallery-mode (WGM) microlasers by multiphoton femtosecond laser direct writing (FsLDW). Protein/Rhodamine B (RhB) composite biopolymer was used as optical gain medium innovatively. By adopting high-viscosity aqueous protein ink and optimized scanning mode, protein-based WGM microlasers were customized with exquisite true 3D geometry and smooth morphology. Comparable to previously reported artificial polymers, protein-based WGM microlasers here were endowed with valuable performances including steady operation in air and even in aqueous environments, and a higher quality value (Q) of several thousands (without annealing). Due to the "smart" feature of protein hydrogel, lasing spectrum was responsively adjusted by step of ~0.4 nm blueshift per 0.83-mmol/L Na2SO4 concentration change (0 ~ 5-mmol/L in total leading to ~2.59-nm blueshift). Importantly, other performances including Q, FWHM, FSR, peak intensities, exhibited good stability during adjustments. So, these protein-based 3D WGM microlasers might have potential in applications like optical biosensing and tunable "smart" biolasers, useful in novel photonic biosystems and bioengineering.

Aqueous multiphoton lithography with multifunctional silk-centred bio-resists.

Silk and silk fibroin, the biomaterial from nature, nowadays are being widely utilized in many cutting-edge micro/nanodevices/systems via advanced micro/nanofabrication techniques. Herein, for the first time to our knowledge, we report aqueous multiphoton lithography of diversiform-regenerated-silk-fibroin-centric inks using noncontact and maskless femtosecond laser direct writing (FsLDW). Initially, silk fibroin was FsLDW-crosslinked into arbitrary two/three-dimensional micro/nanostructures with good elastic properties merely using proper photosensitizers. More interestingly, silk/metal composite micro/nanodevices with multidimension-controllable metal content can be FsLDW-customized through laser-induced simultaneous fibroin oxidation/crosslinking and metal photoreduction using the simplest silk/Ag(+) or silk/[AuCl4](-) aqueous resists. Noticeably, during FsLDW, fibroin functions as biological reductant and matrix, while metal ions act as the oxidant. A FsLDW-fabricated prototyping silk/Ag microelectrode exhibited 10(4)-Ω(-1 ) m(-1)-scale adjustable electric conductivity. This work not only provides a powerful development to silk micro/nanoprocessing techniques but also creates a novel way to fabricate multifunctional metal/biomacromolecule complex micro/nanodevices for applications such as micro/nanoscale mechanical and electrical bioengineering and biosystems.