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Osteoarthritis (OA) is a common degenerative joint disease in older adults. A number of previous studies have demonstrated that natural flavonoids can serve as promising therapeutic drugs for OA. Kaempferol, a phytochemical ingredient mainly present in various fruits, has exhibited its prominent anti-inflammatory and antioxidant effects in numerous diseases. However, whether Kaempferol ameliorates the deterioration of arthritis remains to be elucidated. The aim of the present study was to investigate the therapeutic role of Kaempferol on OA in rat chondrocytes. The results revealed that Kaempferol significantly inhibited the interleukin (IL)-1β-induced protein expression of inflammatory mediators such as inducible nitric oxide synthase and cyclo-oxygenase-2. In addition, the common matrix degrading enzymes [matrix metalloproteinase (MMP)-1, MMP-3, MMP-13 and a disintegrin and metalloproteinase with thrombospondin motif-5] induced by IL-1β were also suppressed by Kaempferol, and consequently abolished the degradation of collagen II. Furthermore, the anti-inflammatory effect of Kaempferol was mediated by the inhibition of the mitogen activated protein kinase-associated extracellular signal-regulated kinase and P38 signaling pathways. These results collectively indicated that Kaempferol can potentially prevent OA development and serve as a novel pharmacological target in the treatment of OA.

Interleukin-1β (IL-1β)-induced inflammatory response is associated with osteoarthritis (OA) and its development. Histone deacetylase (HDAC) may be involved in regulating this pathogenesis, but the mechanism has yet to be elucidated. The aim of the present study was to investigate the mechanism underlying the regulation of IL-1β-stimulated catabolic degradation of cartilage by HDAC. An in vitro model of OA was generated using rat articular chondrocytes (rACs) treated with IL-1β. The role of HDAC in IL-1β-induced gene expression was investigated using HDAC inhibitors and specific small interfering RNAs (siRNAs). The association of diverse mitogen-activated protein kinase (MAPK) pathways was examined. The IL-1β-induced expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5, and the production of collagen X and cyclo-oxygenase-2 in rACs was accompanied by the expression of HDAC4 and HDAC8, and were significantly downregulated by HDAC inhibitors and specific siRNAs. IL-1β-induced activation of extracellular signal-regulated kinase was downregulated by the HDAC inhibitor Trichostatin A, but not significantly by PCI-34051. The activation of c-Jun N-terminal kinase was observably downregulated by the latter, but only slightly by the former. These results suggest that HDAC4 and HDAC8 may serve as key upstream mediators of MAPK in regulating the IL-1β-induced cartilage catabolic and degradation. Therefore, inhibiting HDAC4 or HDAC8 or both may be a promising therapeutic strategy in preventing and treating OA.

To meet the multi-cooperation production demand of enterprises, the distributed permutation flow shop scheduling problem (DPFSP) has become the frontier research in the field of manufacturing systems. In this paper, we investigate the DPFSP by minimizing a makespan criterion under the constraint of sequencedependent setup times. To solve DPFSPs, significant developments of some metaheuristic algorithms are necessary. In this context, a simple and effective improved iterated greedy (NIG) algorithm is proposed to minimize makespan in DPFSPs. According to the features of DPFSPs, a two-stage local search based on single job swapping and job block swapping within the key factory is designed in the proposed algorithm. We compare the proposed algorithm with state-of-the-art algorithms, including the iterative greedy algorithm (2019), iterative greedy proposed by Ruiz and Pan (2019), discrete differential evolution algorithm (2018), discrete artificial bee colony (2018), and artificial chemical reaction optimization (2017). Simulation results show that NIG outperforms the compared algorithms.

Osteoarthritis (OA) is a degenerative joint disease frequently seen in the elderly population. Sinapic acid (SA), a commonly found phenolic acid, has been pharmacologically evaluated for its anti-inflammation effects in various studies. To explore its potential therapeutic role for OA, rat chondrocytes were treated with IL-1β (10 ng/ml) with different concentrations of SA in vitro. Our study revealed that SA could inhibit the IL-1β-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2). Consistent with these findings, the increased protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase (Cox)-2 could also be downregulated by SA. Moreover, SA could also suppress the IL-1β-induced expression of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) in chondrocytes. Furthermore, our data found that SA could suppress the IL-1β-induced mitogen-activated protein kinase (MAPK) pathway activation. In general, this paper elucidates that sinapic acid inhibits the IL-1β-induced inflammation via MAPK pathways and may be a good agent for the treatment of OA.

Cell penetrating peptides (CPPs) are a series of promising carriers for delivering exogenous DNA to living cells. Among them, the combination of the human immunodeficiency virus TAT protein (TAT) with the SV40 large T protein nuclear localization signal (NLS) to form NLS-TAT performs well. In the present study, we took advantage of this new carrier to deliver transforming growth factor-beta 3 (TGFβ3) genes. TGFβ3 was expressed by the pEGFP-N1 vector following transfection of rat precartilaginous stem cells (PSCs), which promoted hTGFβ3 protein self-expression. At 24, 48, 72, and 120 h after transfection, the expression levels of hTGFβ3 were found to be elevated as compared with the control. The expression of hTGFβ3 was found to mediate the chondrogenic effect of PSCs. Thus, we determined the expression of the chondrogenesis-related genes type II collagen, Sox 9, and aggrecan in PSCs at 24, 48, 72, and 120 h after transfection. We found that their transcription and translation was augmented, which indicated a trend of active chondrogenesis in the PSCs. Our results demonstrated that NLS-TAT had the ability to deliver exogenous DNA into rat PSCs and could be actively expressed. This process successfully promoted PSC chondrogenesis. Additionally, PSC, may represent a new type of stem cells, and thus show great potential in regenerative repair following cartilage injury.