By delivering the concept of clean hydrogen energy and green catalysis to the biomedical field, engineering of hydrogen-generating nanomaterials for treatment of major diseases holds great promise. Leveraging virtue of versatile abilities of Pd hydride nanomaterials in high/stable hydrogen storage, self-catalytic hydrogenation, near-infrared (NIR) light absorption and photothermal conversion, here we utilize the cubic PdH0.2 nanocrystals for tumour-targeted and photoacoustic imaging (PAI)-guided hydrogenothermal therapy of cancer. The synthesized PdH0.2 nanocrystals have exhibited high intratumoural accumulation capability, clear NIR-controlled hydrogen release behaviours, NIR-enhanced self-catalysis bio-reductivity, high NIR-photothermal effect and PAI performance. With these unique properties of PdH0.2 nanocrystals, synergetic hydrogenothermal therapy with limited systematic toxicity has been achieved by tumour-targeted delivery and PAI-guided NIR-controlled release of bio-reductive hydrogen as well as generation of heat. This hydrogenothermal approach has presented a cancer-selective strategy for synergistic cancer treatment.

CD36 (also known as scavenger receptor B2) is a multifunctional receptor that mediates the binding and cellular uptake of long-chain fatty acids, oxidized lipids and phospholipids, advanced oxidation protein products, thrombospondin and advanced glycation end products, and has roles in lipid accumulation, inflammatory signalling, energy reprogramming, apoptosis and kidney fibrosis. Renal CD36 is mainly expressed in tubular epithelial cells, podocytes and mesangial cells, and is markedly upregulated in the setting of chronic kidney disease (CKD). As fatty acids are the preferred energy source for proximal tubule cells, a reduction in fatty acid oxidation in CKD affects kidney lipid metabolism by disrupting the balance between fatty acid synthesis, uptake and consumption. The outcome is intracellular lipid accumulation, which has an important role in the pathogenesis of kidney fibrosis. In experimental models, antagonist blockade or genetic knockout of CD36 prevents kidney injury, suggesting that CD36 could be a novel target for therapy. Here, we discuss the regulation and post-translational modification of CD36, its role in renal pathophysiology and its potential as a biomarker and as a therapeutic target for the prevention of kidney fibrosis.

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Long non-coding RNAs (lncRNAs) play an important role in gene regulation and are involving in diverse cellular processes. However, their roles in reprogramming of gene expression profiles during lineage commitment and maturation of mesenchymal stem cells (MSCs) remain poorly understood. In the current study, we characterize the expression of a lncRNA, HoxA-AS3, during the differentiation of MSCs. We showed that HoxA-AS3 is increased upon adipogenic induction of MSCs, while HoxA-AS3 remains unaltered during osteogenic induction. Silencing of HoxA-AS3 in MSCs resulted in decreased adipogenesis and expression of adipogenic markers, PPARG, CEBPA, FABP4 and ADIPOQ. Conversely, knockdown of HoxA-AS3 expression in MSCs exhibited an enhanced osteogenesis and osteogenic markers expression, including RUNX2, SP7, COL1A1, IBSP, BGLAP and SPP1. Mechanistically, HoxA-AS3 interacts with Enhancer Of Zeste 2 (EZH2) and is required for H3 lysine-27 trimethylation (H3K27me3) of key osteogenic transcription factor Runx2. Our data reveal that HoxA-AS3 acts as an epigenetic switch that determines the lineage specification of MSC.

The hydrogen molecule is recognized as a high potential to attenuate toxic side effects of chemotherapy and also enhance chemotherapeutic efficacy, and the development of a novel hydrogen‐generating prodrug for facile, safe, and efficient hydrogen delivery is vitally important for combined hydrogenochemotherapy but is still challenging. Here, targeting gastric cancer, a 2D magnesium boride nanosheet (MBN) is synthesized as a new type of acid‐responsive hydrogen‐releasing prodrug by an ultrasound‐assisted chemical etching route, which is used to realize hydrogenochemotherapy by combination of facile oral administration of polyvinylpyrrolidone (PVP)‐encapsulating MBN (MBN@PVP) pills with routine intravenous injection of doxorubicin (DOX). The MBN@PVP pill has high stability in normal tissues/blood environments as well as high gastric acid‐responsiveness with sustained release behavior, which matches well with its metabolism rate in the stomach in great favor of continuous and long‐term hydrogen administration. Hydrogenochemotherapy with DOX+MBN@PVP has remarkably prolonged the survival time of gastric tumor‐bearing mice by reducing the toxic side effects of chemotherapy. The mechanism for therapeutic synergy and side effect attenuation of hydrogenochemotherapy is discovered to be derived from the selectivity of hydrogen molecules in inhibiting aerobic respiration of gastric cells but activating aerobic respiration of normal cells including marrow mesenchymal stem cells and cardiac, hepatic, and splenic cells.