Wogonin alleviates liver injury in sepsis through Nrf2-mediated NF-κB signalling suppression.

Sepsis is a life-threatening organ dysfunction syndrome, and liver is a susceptible target organ in sepsis, because the activation of inflammatory pathways contributes to septic liver injury. Oxidative stress has been documented to participate in septic liver injury, because it not only directly induces oxidative genotoxicity, but also exacerbates inflammatory pathways to potentiate damage of liver. Therefore, to ameliorate oxidative stress is promising for protecting liver in sepsis. Wogonin is the compound extracted from the medicinal plant Scutellaria baicalensis Geogi and was found to exert therapeutic effects in multiple inflammatory diseases via alleviation of oxidative stress. However, whether wogonin is able to mitigate septic liver injury remains unknown. Herein, we firstly proved that wogonin treatment could improve survival of mice with lipopolysaccharide (LPS)- or caecal ligation and puncture (CLP)-induced sepsis, together with restoration of reduced body temperature and respiratory rate, and suppression of several pro-inflammatory cytokines in circulation. Then, we found that wogonin effectively alleviated liver injury via potentiation of the anti-oxidative capacity. To be specific, wogonin activated Nrf2 thereby promoting expressions of anti-oxidative enzymes including NQO-1, GST, HO-1, SOD1 and SOD2 in hepatocytes. Moreover, wogonin-induced Nrf2 activation could suppress NF-κB-regulated up-regulation of pro-inflammatory cytokines. Ultimately, we provided in vivo evidence that wogonin activated Nrf2 signalling, potentiated anti-oxidative enzymes and inhibited NF-κB-regulated pro-inflammatory signalling. Taken together, this study demonstrates that wogonin can be the potential therapeutic agent for alleviating liver injury in sepsis by simultaneously ameliorating oxidative stress and inflammatory response through the activation of Nrf2.

Dental injuries at the Xi'an, China Stomatological Hospital: A Retrospective Study.

BACKGROUND/AIM: In order to enrich epidemiological knowledge regarding traumatic dental injuries (TDI) in China, and to further improve the treatment, prevention and education of TDI, the aim of this study was to retrospectively analyze the TDI that presented to the emergency dental department at the Stomatological Hospital in Xi'an, China. METHODS: This retrospective study included all first-visit patients who presented with TDI at the Stomatological Hospital affiliated with the Fourth Military Medical University in Xi'an, China, between January 2013 and June 2019. Data were extracted using the terms of diagnosis of TDI from the hospital database. RESULTS: Overall, 965 (606 males and 359 females) files were reviewed. The average age was 22.8 ± 13.4 years. Among the 2059 teeth injured (average of 2.1 teeth per patient), the maxillary incisors (1751; 85.0%) were the most prevalent teeth to present with injuries, while the main types of injuries were concussions (14.8%) enamel-dentin-fractures (14.50%) and enamel-dentin-pulp fractures (14.0%). After initial examination and diagnosis, 4.2% patients refused treatment. CONCLUSIONS: The epidemiological statistics of TDI in Xi'an, China show consistency with other studies from around the world, but they also vary in diagnosis proportion and the choice of treatments. This information may further instruct treatment, prevention and emergency resources distribution to target the high-risk groups.

Characterization of the complete mitochondrial genome of the Qiaoke sheep (Ovis aries).

Qiaoke sheep (Ovis aries) is a local sheep breed in Gansu province, China. It is a kind of Tibetan sheep that used for both meat and wool after long-term breeding. In this paper, the complete mitochondrial genome of Qiaoke sheep was sequenced. The total length of the mitochondrial genome is 16616 bp, and the base composition is 33.65% A, 13.14% G, 25.88% C and 27.33% T. The genome has a total of 37 genes, including 13 protein-coding genes, 22 tRNA genes, two ribosomal RNA genes and a control region (D-loop region). This complete sequence would enlarge useful genomic information for further studies.

Melatonin induces the rejuvenation of long-term ex vivo expanded periodontal ligament stem cells by modulating the autophagic process.

BACKGROUND: Stem cells that have undergone long-term ex vivo expansion are most likely functionally compromised (namely cellular senescence) in terms of their stem cell properties and therapeutic potential. Due to its ability to attenuate cellular senescence, melatonin (MLT) has been proposed as an adjuvant in long-term cell expansion protocols, but the mechanism underlying MLT-induced cell rejuvenation remains largely unknown. METHODS: Human periodontal ligament stem cells (PDLSCs) were isolated and cultured ex vivo for up to 15 passages, and cells from passages 2, 7, and 15 (P2, P7, and P15) were used to investigate cellular senescence and autophagy change in response to long-term expansion and indeed the following MLT treatment. Next, we examined whether MLT could induce cell rejuvenation by restoring the autophagic processes of damaged cells and explored the underlying signaling pathways. In this context, cellular senescence was indicated by senescence-associated ß-galactosidase (SA-ß-gal) activity and by the expression of senescence-related proteins, including p53, p21, p16, and γ-H2AX. In parallel, cell autophagic processes were evaluated by examining autophagic vesicles (by transmission electronic microscopy), autophagic flux (by assessing mRFP-GFP-LC3-transfected cells), and autophagy-associated proteins (by Western blot assay of Atg7, Beclin-1, LC3-II, and p62). RESULTS: We found that long-term in vitro passaging led to cell senescence along with impaired autophagy. As expected, MLT supplementation not only restored cells to a younger state but also restored autophagy in senescent cells. Additionally, we demonstrated that autophagy inhibitors could block MLT-induced cell rejuvenation. When the underlying signaling pathways involved were investigated, we found that the MLT receptor (MT) mediated MLT-related autophagy restoration by regulating the PI3K/AKT/mTOR signaling pathway. CONCLUSIONS: The present study suggests that MLT may attenuate long-term expansion-caused cellular senescence by restoring autophagy, most likely via the PI3K/AKT/mTOR signaling pathway in an MT-dependent manner. This is the first report identifying the involvement of MT-dependent PI3K/AKT/mTOR signaling in MLT-induced autophagy alteration, indicating a potential of autophagy-restoring agents such as MLT to be used in the development of optimized clinical-scale cell production protocols.

Exosomes derived from P2X7 receptor gene-modified cells rescue inflammation-compromised periodontal ligament stem cells from dysfunction.

Although cellular therapy has been proposed for inflammation-related disorders such as periodontitis for decades, clinical application has been unsuccessful. One explanation for these disappointing results is that the functions of stem cells are substantially compromised when they are transplanted into an inflammatory in vivo milieu. Considering the previous finding that P2X7 receptor (P2X7R) gene modification is able to reverse inflammation-mediated impairment of periodontal ligament stem cells (PDLSCs), we further hypothesized that cells subjected to P2X7R gene transduction also exert influences on other cells within an in vivo milieu via an exosome-mediated paracrine mechanism. To define the paracrine ability of P2X7R gene-modified cells, P2X7R gene-modified stem cell-derived conditional medium (CM-Ad-P2X7) and exosomes (Exs-Ad-P2X7) were used to incubate PDLSCs. In an inflammatory osteogenic microenvironment, inflammation-mediated changes in PDLSCs were substantially reduced, as shown by quantitative real-time PCR (qRT-PCR) analysis, Western blot analysis, alkaline phosphatase (ALP) staining/activity assays, and Alizarin red staining. In addition, the Agilent miRNA microarray system combined with qRT-PCR analysis revealed that miR-3679-5p, miR-6515-5p, and miR-6747-5p were highly expressed in Exs-Ad-P2X7. Further functional tests and luciferase reporter assays revealed that miR-3679-5p and miR-6747-5p bound directly to the GREM-1 protein, while miR-6515-5p bound to the GREM-1 protein indirectly; these effects combined to rescue inflammation-compromised PDLSCs from dysfunction. Thus, in addition to maintaining their robust functionality under inflammatory conditions, P2X7R gene-modified stem cells may exert positive influences on their neighbors via a paracrine mechanism, pointing to a novel strategy for modifying the harsh local microenvironment to accommodate stem cells and promote improved tissue regeneration.

Role of the P2X7 receptor in inflammation-mediated changes in the osteogenesis of periodontal ligament stem cells.

Accumulating evidence indicates that the pluripotency of periodontal ligament stem cells (PDLSCs) is compromised under inflammatory conditions; however, the underlying mechanisms remain largely unexplored. In this study, we hypothesize that the P2X7 receptor (P2X7R) is a key molecule linked to inflammation-associated impairment of PDLSCs. We first investigated P2X7R expression in PDLSCs under normal and inflammatory conditions and then determined the effect of a P2X7R agonist (BzATP) or antagonist (BBG) on PDLSC osteogenesis under various conditions. Gene-modified PDLSCs were used to further examine the role of P2X7R and the signaling pathway underlying P2X7R-enhanced osteogenesis. We found that inflammatory conditions decreased P2X7R expression in PDLSCs and reduced osteogenesis in these cells. In addition, activation of P2X7R by BzATP or overexpression of P2X7R via gene transduction reversed the inflammation-mediated decrease in PDLSC osteogenic differentiation. When selected osteogenesis-related signaling molecules were screened, the PI3K-AKT-mTOR pathway was identified as potentially involved in P2X7R-enhanced PDLSC osteogenesis. Our data reveal a crucial role for P2X7R in PDLSC osteogenesis under inflammatory conditions, suggesting a new therapeutic target to reverse or rescue inflammation-mediated changes in PDLSCs for future mainstream therapeutic uses.

L-type voltage-gated calcium channels in stem cells and tissue engineering.

L-type voltage-gated calcium ion channels (L-VGCCs) have been demonstrated to be the mediator of several significant intracellular activities in excitable cells, such as neurons, chromaffin cells and myocytes. Recently, an increasing number of studies have investigated the function of L-VGCCs in non-excitable cells, particularly stem cells. However, there appear to be no systematic reviews of the relationship between L-VGCCs and stem cells, and filling this gap is prescient considering the contribution of L-VGCCs to the proliferation and differentiation of several types of stem cells. This review will discuss the possible involvement of L-VGCCs in stem cells, mainly focusing on osteogenesis mediated by mesenchymal stem cells (MSCs) from different tissues and neurogenesis mediated by neural stem/progenitor cells (NSCs). Additionally, advanced applications that use these channels as the target for tissue engineering, which may offer the hope of tissue regeneration in the future, will also be explored.

[Clinical value of the detection of hepatitis C virus core antigen].

AIM: To explore the value of detecting hepatitis C virus core antigen in HCV infected diseases. METHODS: The HCV-RNA was tested by fluorescent quantitative polymerase chain reaction (FQ-PCR). The core antigens of HCV and anti-HCV were tested by enzyme-linked immunosorbent assay (ELISA). RESULTS: The positive rate of HCV-RNA in 191 patients was 71.2%, about 136 in 191. The positive rate of anti-HCV was 97.4%, about 186 in 191. The positive rate of HCV core antigen was 33.0%, about 63 in 191. After antiviral therapy for 2 patients,their HCV-RNA and anti-HCV were detected negative but their HCV core antigen was detected positive. In another patient, his anti-HCV was negative but his HCV core antigen was positive. CONCLUSION: As a supplemental test for anti-HCV examination the detection of HCV core antigen is of important clinical value in HCV infection diagnosis.