Baicalin inhibits colistin sulfate-induced apoptosis of PC12 cells

Baicalin, a type of flavonoid extracted from the dried root of Scutellaria baicalensis georgi, has been shown to effectively inhibit cell apoptosis. Therefore, we assumed that baicalin would suppress colistin sulfate-induced neuronal apoptosis. PC12 cells exposed to colistin sulfate （62.5-500 μg/mL） for 24 hours resulted in PCl2 cell apoptosis. In addition, caspase-3 activity, lactate dehydrogenase level and free radical content increased in a dose-dependent manner. Subsequently, PC12 cells were pretreated with baicalin （25, 50 and 100 pg/mL）, and exposed to 125 pg/mL colistin sulfate. Cell morphology markedly changed, and cell viability increased. Moreover, caspase-3 activity, lac- tate dehydrogenase level and free radical content decreased. Results indicated that baicalin inhib- ited colistin sulfate-induced PC12 cell apoptosis by suppressing free radical injury, and reducing caspase-3 activity and lactate dehydrogenase activity.

Morphological Characteristics of the Dorsal Skin of Two Hynobiids and Their Adaptive Role in Aquatic and Terrestrial Habitats

The morphological characteristics of the dorsal skin of trunk in two species of hynobiid salamanders, Batrachuperus pinchonii and Hynobius chinensis were examined by light microscopy. The basic structures of the skin in the two species are similar and consist of two layers： epidermis and dermis. The epidermis consists of stratum corneum, stratum intermedium and stratum germinativum, while the dermis is composed of a stratum spongiosum and stratum compactum. However, some species-specific variation has been identified （e.g., the distribution of capillary vessels and gland cells, and the thickness of skin）. H. chinensis is a terrestrial species and only lives in water during breeding period, but B. pinchonii is aquatic and remains aquatic throughout its lifetime. The differences in the distribution of capillary vessels and gland cells are related to their different habitats, and show a morphological adaptation.

CCL5 deficiency promotes liver repair by improving inflammation resolution and liver regeneration through M2 macrophage polarization

Despite the diverse etiologies of drug-induced liver injury(DILI),innate immunity activation is a common feature involved in DILI progression.However,the involvement of innate immunity regulation in inflammation resolution and liver regeneration in DILI remains obscure.Herein,we identified the chemokine CCL5 as a central mediator of innate immunity regulation in the pathogenesis of DILI.First,we showed that serum and hepatic CCL5 levels are elevated in both DILI patients and an APAP-induced liver injury(AILI)mouse model.Interestingly,both nonparenchymal cells and stressed hepatocytes are cell sources of CCL5 induction in response to liver injury.Functional experiments showed that CCL5 deficiency has no effect on the early phase of AILI but promotes liver repair in the late phase mainly by promoting inflammation resolution and liver regeneration,which are associated with an increased number of hepatic M2 macrophages.Mechanistically,CCL5 can directly activate M1 polarization and impede M2 polarization through the CCR1-and CCR5-mediated activation of the MAPK and NF-κB pathways.We then showed that CCL5 inhibition mediated by either a CCL5-neutralizing antibody or the antagonist Met-CCL5 can greatly alleviate liver injury and improve survival in an AILI mouse model.Our data demonstrate CCL5 induction during DILI,identify CCL5 as a novel innate immunity regulator in macrophage polarization,and suggest that CCL5 blockage is a promising therapeutic strategy for the treatment of DILI.

Emerging roles of DJ-1 in liver diseases through regulation of oxidative stress and immune response

Reactive oxygen species(ROS)and immune response play critical roles in the progression of liver diseases.DJ-1,also known as Parkinson disease 7(Park7),is extensively expressed in cells and tissues,where it governs numerous biological functions including chaperone activity,protease function,transcriptional and mitochondrial regulation,and ROS modulation.Moreover,we have established that DJ-1 plays a critical role in initiating an inflammatory response by modulating ROS generation.Therefore,DJ-1 may play an important role in the progression of liver diseases by modulating ROS and the immune response.Recently,we have shown that DJ-1 deficiency negatively regulates proliferation of hepatic progenitor cells(HPCs)by impairing the formation of HPC-associated fibrosis and inflammatory niches.Deficiency of DJ-1 ameliorates liver fibrosis by inhibiting hepatic ROS production and inflammation;moreover,in a classic diethylnitrosamine(DEN)-mediated hepatocellular carcinoma(HCC)mouse model,deletion of DJ-1 ameliorates tumorigenesis and HCC cell proliferation by regulating hepatic inflammation and reducing the activity of the interleukin 6/signal transducer and activator of transcription 3(IL-6/STAT3)signaling pathway.Taken together,these data suggest a critical function for,and therapeutic value of,DJ-1 in treatment of liver diseases.The aim of this review is to summarize these functions and the underlying molecular mechanisms of DJ-1 in liver diseases,and to highlight the potential therapeutic value and future research direction of DJ-1 in liver diseases.