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The inflammatory environment and excessive chondrocyte apoptosis have been demonstrated to play crucial roles in the onset of osteoarthritis (OA). Hydrogen sulfide (H2S), a gaseous signalling molecule, exerts an inhibitory effect on inflammation and apoptosis in several degenerative diseases. However, the protective effect of H2S against OA has not been fully clarified, and its underlying mechanism should be examined further. In the current study, the role of endogenous H2S in the pathogenesis of OA and its protective effects on interleukin (IL)‐1β‐induced chondrocytes were identified. Our data revealed decreased H2S expression in both human degenerative OA cartilage tissue and IL‐1β‐induced chondrocytes. Pretreatment with the H2S donor sodium hydrosulfide (NaHS) dramatically attenuated IL‐1β‐induced overproduction of inflammatory cytokines and improved the balance between anabolic and catabolic chondrocyte capacities, and these effects were dependent on PI3K/AKT pathway‐mediated inhibition of nuclear factor kappa B (NF‐κB). Moreover, mitochondrial dysfunction‐related apoptosis was significantly reversed by NaHS in IL‐1β‐stimulated chondrocytes. Mechanistically, NaHS partially suppressed IL‐1β‐induced phosphorylation of the mitogen‐activated protein kinase (MAPK) cascades. Furthermore, in the destabilization of the medial meniscus mouse model, OA progression was ameliorated by NaHS administration. Taken together, these results suggest that H2S may antagonize IL‐1β‐induced inflammation and mitochondrial dysfunction‐related apoptosis via selective suppression of the PI3K/Akt/NF‐κB and MAPK signalling pathways, respectively, in chondrocytes and may be a potential therapeutic agent for the treatment of OA. [ABSTRACT FROM AUTHOR]

Stem cell technology can be used in tissue engineering and regenerative medicine to transplant stem cells of somatic, embryonic, or induced pluripotent origin, which have tremendous potential for the treatment of currently incurable diseases. Stem cells can maintain their stemness through their self-renewal capability while promoting tissue repair and regeneration through differentiation into various target tissue cells. These two major processes of stem cell biology are precisely regulated via extracellular and intracellular signals. Gaseous signaling molecules have recently been identified to play important roles in both physiology and pathophysiology, and inhalable nitric oxide (iNO) has even been applied as a therapeutic agent. Compared with chemical formulations, these molecules have lower molecular weights and are more likely to pass through the blood-brain barrier and between cells. Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H 2 S), three major gaseous signaling molecules involved in biological functions, are emerging as regulators of stem cell processes such as self-renewal, differentiation, survival, anti-apoptotic effects, proliferation, and immune rejection. Although many reviews concerning the roles of gaseous signaling molecules in different diseases or systems are available, few have focused on the roles of these molecules in the regulation of stem cells. Therefore, the aim of this paper is to systematically review the current literature on the functions and mechanisms of the gaseous signaling molecules NO, H 2 S, and CO in different types of stem cells and to summarize the effects of these molecules on stem cell biology and in therapy.

In the present study, we detected CXC chemokine receptor-2 (CXCR2) CXCR2 expression in patients with colorectal cancer (CRC) and investigated the correlation of CXCR2 expression with clinicopathological variables. CXCR2 expression levels in 46 cancerous tissues, 20 colonic benign tumour tissues, and 30 normal colonic mucosa tissues were examined at both the mRNA level and protein level by using reverse transcription polymerase chain reaction (RT-PCR) and two-step immunohistochemical staining, respectively. We found that the positive rate of CXCR2 protein expression in cancer tissue samples was 69.6%. RT-PCR results confirmed that CXCR2 expression was significantly higher in tumour tissues compared with benign tumour and normal mucosa tissues (P < 0.05). When 46 colorectal cancer patients were divided into groups according to the clinical stage, lymph node metastasis and liver metastasis, we found that CXCR2 expression increased in patients with lymph node metastasis (P < 0.05), and its expression was much higher in stage III and IV cancers than stage I and II cancers. These findings suggest that CXCR2 expression in CRC patients may be a potential molecular biomarker for evaluation of tumour growth and invasion.