Advances in the treatment of pancreatic cancer with traditional Chinese medicine.

Pancreatic cancer is a common malignancy of the digestive system. With a high degree of malignancy and poor prognosis, it is called the "king of cancers." Currently, Western medicine treats pancreatic cancer mainly by surgical resection, radiotherapy, and chemotherapy. However, the curative effect is not satisfactory. The application of Traditional Chinese Medicine (TCM) in the treatment of pancreatic cancer has many advantages and is becoming an important facet of comprehensive clinical treatment. In this paper, we review current therapeutic approaches for pancreatic cancer. We also review the protective effects shown by TCM in different models and discuss the potential molecular mechanisms of these.

Fatty acid sensing GPCR (GPR84) signaling safeguards cartilage homeostasis and protects against osteoarthritis.

It is well known that free fatty acids (FFAs) have beneficial effects on the skeletal system, however, which fatty acid sensing GPCR(s) and how the GPCR(s) regulating cartilage development and osteoarthritis (OA) pathogenesis is largely unknown. In this study, we found Gpr84, a receptor for medium-chain FFAs (MCFA), was the only FFA-sensing GPCR in human and mouse chondrocytes that exhibited elevated expression when stimulated by interleukin (IL)-1ß. Gpr84-deficiency upregulated cartilage catabolic regulator expression and downregulated anabolic factor expression in the IL-1ß-induced cell model and the destabilization of the medial meniscus (DMM)-induced OA mouse model. Gpr84-/- mice exhibited an aggravated OA phenotype characterized by severe cartilage degradation, osteophyte formation and subchondral bone sclerosis. Moreover, activating Gpr84 directly enhanced cartilage extracellular matrix (ECM) generation while knockout of Gpr84 suppressed ECM-related gene expression. Especially, the agonists of GPR84 protected human OA cartilage explants against degeneration by inducing cartilage anabolic factor expression. At the molecular level, GPR84 activation inhibited IL-1ß-induced NF-κB signaling pathway. Furthermore, deletion of Gpr84 had little effect on articular and spine cartilaginous tissues during skeletal growth. Together, all of our results demonstrated that fatty acid sensing GPCR (Gpr84) signaling played a critical role in OA pathogenesis, and activation of GPR84 or MCFA supplementation has potential in preventing the pathogenesis and progression of OA without severe cartilaginous side effect.

The Tumorigenic Effect of Sphingosine Kinase 1 and Its Potential Therapeutic Target.

Sphingosine kinase 1 (SPHK1) regulates cell proliferation and survival by converting sphingosine to the signaling mediator sphingosine 1-phosphate (S1P). SPHK1 is widely overexpressed in most cancers, promoting tumor progression and is associated with clinical prognosis. Numerous studies have explored SPHK1 as a promising target for cancer therapy. However, due to insufficient knowledge of SPHK1 oncogenic mechanisms, its inhibitors' therapeutic potential in preventing and treating cancer still needs further investigation. In this review, we summarized the metabolic balance regulated by the SPHK1/S1P signaling pathway and highlighted the oncogenic mechanisms of SPHK1 via the upregulation of autophagy, proliferation, and survival, migration, angiogenesis and inflammation, and inhibition of apoptosis. Drug candidates targeting SPHK1 were also discussed at the end. This review provides new insights into the oncogenic effect of SPHK1 and sheds light on the future direction for targeting SPHK1 as cancer therapy.

Radioprotective Effect of Flavonoids on Ionizing Radiation-Induced Brain Damage.

Patients receiving brain radiotherapy may suffer acute or chronic side effects. Ionizing radiation induces the production of intracellular reactive oxygen species and pro-inflammatory cytokines in the central nervous system, leading to brain damage. Complementary Chinese herbal medicine therapy may reduce radiotherapy-induced side effects. Flavonoids are a class of natural products which can be extracted from Chinese herbal medicine and have been shown to have neuroprotective and radioprotective properties. Flavonoids are effective antioxidants and can also inhibit regulatory enzymes or transcription factors important for controlling inflammatory mediators, affect oxidative stress through interaction with DNA and enhance genomic stability. In this paper, radiation-induced brain damage and the relevant molecular mechanism were summarized. The radio-neuro-protective effect of flavonoids, i.e., antioxidant, anti-inflammatory and maintaining genomic stability, were then reviewed. We concluded that flavonoids treatment may be a promising complementary therapy to prevent radiotherapy-induced brain pathophysiological changes and cognitive impairment.

Effects of Grape Seed Proanthocyanidin Extract on Obesity.

Obesity is a chronic metabolic disease resulting from excessive fat accumulation and/or abnormal distribution caused by multiple factors. As a major component of metabolic syndrome, obesity is closely related to many diseases such as type 2 diabetes mellitus, hyperlipidemia, hypertension, coronary heart disease, stroke and cancer. Hence, the problem of obesity cannot be ignored, and recent studies have shown that grape seed proanthocyanidin extract (GSPE) has an antiobesity effect. This paper systematically reviews the research progress and potential mechanism of GSPE emphasizing on obesity prevention and treatment.

Anthocyanin suppresses CoCrMo particle-induced osteolysis by inhibiting IKKα/ß mediated NF-κB signaling in a mouse calvarial model.

Wear particle-induced osteolysis and bone resorption have been identified as critical factors of implant failure and total joint revision, in which nuclear factor kappa B (NF-κB) signaling and chronic inflammation have been shown to play key roles. Although anthocyanin is known to have anti-inflammatory function via blocking NF-κB pathway, it is still unclear whether anthocyanin has a protective effect on particle-induced osteolysis. In the present study, we aimed to investigate the detailed effects and the underlying mechanism of anthocyanin on CoCrMo particle-induced osteolysis in a mouse calvavial model. One hundred and twelve male BALB/c mice were divided randomly into four groups: sham group (sham operation and injection with PBS), vehicle group (CoCrMo particle treatment and injection with PBS), low-dose anthocyanin group (CoCrMo particle treatment and injecting anthocyanin with 0.1mg/g/day), and high-dose anthocyanin group (CoCrMo particle treatment and injecting anthocyanin with 0.4mg/g/day). Mice were sacrificed after two weeks, harvesting the calvariae tissue for in depth analysis by micro-CT, histomorphometry, immunohistochemical and molecular biology analysis. As expected, anthocyanin markedly inhibited CoCrMo particle-induced inflammatory infiltration and decreased bone loss in vivo. Anthocyanin also reversed the increase in the ratio of receptor activator of nuclear factor kappa B ligand (RANKL)/osteoproteger (OPG) and suppressed osteoclast formation in CoCrMo particle-stimulated calvaria. Additionally, anthocyanin significantly reduced the expression and secretion of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in the calvaria of CoCrMo-stimulated mice. Furthermore, we confirmed that anthocyanin attenuated osteolysis by blocking NF-κB pathway via inhibiting inhibitor of nuclear factor kappa-B kinase α/ß (IKKα/ß) phosphorylation. In conclusion, our study demonstrated that anthocyanin can protect against CoCrMo particle-induced inflammatory osteolysis via inhibiting the IKKα/ß-NF-κB pathway, and have a potential therapeutic effect on the treatment of wear particle-induced osteolysis.

[Effects of stabilization treatment on migration and transformation of heavy metals in mineral waste residues].

Different forms of heavy metals in soil will produce different environmental effects, and will directly influence the toxicity, migration and bioavailability of heavy metals. This study used lime, fly ash, dried sludge, peanut shells as stabilizers in the treatment of heavy metals in mineral waste residues. Morphological analyses of heavy metal, leaching experiments, potted plant experiments were carried out to analyze the migration and transformation of heavy metals. The results showed that after adding stabilizers, the pH of the acidic mineral waste residues increased to more than neutral, and the organic matter content increased significantly. The main existing forms of As, Pb, and Zn in the mineral waste residues were the residual. The contents of exchangeable and organic matter-bound As decreased by 65.6% and 87.7% respectively after adding fly ash, dried sludge and peanut shells. Adding lime, fly ash and peanut shells promoted the transformation of As from the Fe-Mn oxide-bound to the carbonate-bound, and adding lime and fly ash promoted the transformation of Pb and Zn from the exchangeable, Fe-Mn oxide-bound, organic matter-bound to the residual. After the early stage of the stabilization treatment, the contents of As, Pb and Zn in the leachate had varying degrees of decline, and adding peanut shells could reduce the contents of As, Pb and Zn in the leachate further. Among them, the content of As decreased most significantly after treatment with fly ash, dried sludge and peanut shells, with a decline of 57.4%. After treatment with lime, fly ash and peanut shells, the content of Zn decreased most significantly, by 24.9%. The addition of stabilizers was advantageous to the germination and growth of plants. The combination of fly ash, dried sludge and peanut shell produced the best effect, and the Vetiveria zizanioides germination rate reached 76% in the treated wasted mineral residues.