OBJECTIVE: To investigate whether auraptene (AUR) exerts a protective effect on acute diquat (DQ)-induced liver injury in mice and explore its underlying mechanisms. METHODS: Forty SPF-grade healthy male C57BL/6 mice were randomly divided into normal control group (Control group), DQ poisoning model group (DQ group), AUR treatment group (DQ+AUR group), and AUR control group (AUR group), with 10 mice in each group. The DQ poisoning model was established via a single intraperitoneal injection of 40 mg/kg DQ aqueous solution (0.5 mL); Control group and AUR group received an equal volume of pure water intraperitoneally. Four hours post-modeling, DQ+AUR group and AUR group were administered 0.5 mg/kg AUR aqueous solution (0.2 mL) by gavage once daily for 7 consecutive days, while Control group and DQ group received pure water. Blood and liver tissues were collected after anesthesia on day 7. Liver ultrastructure was observed by transmission electron microscopy. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured via enzyme-linked immunosorbent assay (ELISA). Hepatic glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were detected using WST-1, thiobarbituric acid (TBA), and enzymatic reaction methods, respectively. Protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and activated caspase-9 in liver tissues was analyzed by Western blotting. RESULTS: Transmission electron microscopy revealed that mitochondria in the Control group exhibited mild swelling, uneven distribution of matrix, and a small number of cristae fractures. In the AUR group, mitochondria showed mild swelling, with no obvious disruption of cristae structure. In the DQ group, mitochondria demonstrated marked swelling and increased volume, matrix dissolution, loss and fragmentation of cristae, and extensive vacuolization. In contrast, the DQ+AUR group showed significantly reduced mitochondrial swelling, volume increase, matrix dissolution, cristae loss and fragmentation, and vacuolization compared to the DQ group. Compared with the DQ group, the DQ+AUR group exhibited significantly lower serum AST levels (U/L: 173.45±23.60 vs. 255.33±41.51), ALT levels (U/L: 51.77±21.63 vs. 100.70±32.35), and hepatic MDA levels (μmol/g: 12.40±2.76 vs. 19.74±4.10), along with higher hepatic GSH levels (mmol/g: 37.65±14.95 vs. 20.58±8.52) and SOD levels (kU/g: 124.10±33.77 vs. 82.81±22.00), the differences were statistically significant (all P < 0.05). Western blotting showed upregulated Nrf2 expression (Nrf2/β-actin: 0.87±0.37 vs. 0.53±0.22) and HO-1 expression (HO-1/β-actin: 1.06±0.22 vs. 0.49±0.08), and downregulated Keap1 expression (Keap1/β-actin: 0.82±0.12 vs. 1.52±0.76) and activated caspase-9 expression (activated caspase-9/β-actin: 1.16±0.28 vs. 1.71±0.30) in the DQ+AUR group compared to the DQ group (all P < 0.05). CONCLUSION AUR attenuates DQ-induced acute liver injury in mice by activating the Keap1/Nrf2 signaling pathway.
Animals ; Male ; Mice ; Mice, Inbred C57BL ; Liver/pathology* ; Chemical and Drug Induced Liver Injury/drug therapy* ; Diquat/poisoning* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress ; Apoptosis ; Coumarins

Soil cadmium (Cd) pollution is one of the major environmental problems globally. Ophiopogon japonicus, a multifunctional plant extensively used in traditional Chinese medicine, has demonstrated potential in environmental remediation. This study investigated the Cd accumulation pattern of O. japonicus under cadmium stress and identified the heavy metal ATPase (HMA) family members in this plant. Our results demonstrated that O. japonicus exhibited a Cd enrichment factor (EF) of 2.75, demonstrating strong potential for soil Cd pollution remediation. Nine heavy metal ATPase (HMA) members of P1B-ATPases were successfully identified from the transcriptome data of O. japonicus, with OjHMA1-OjHMA6 classified as the Zn/Co/Cd/Pb-ATPases and OjHMA7-OjHMA9 as the Cu/Ag-ATPases. The expression levels of OjHMA1, OjHMA2, OjHMA3, and OjHMA7 were significantly up-regulated under Cd stress, highlighting their crucial roles in cadmium ion absorption and transport. The topological analysis revealed that these proteins possessed characteristic transmembrane (TM) segments of the family, along with functional A, P, and N domains involved in regulating ion absorption and release. Metal ion-binding sites (M4, M5, and M6) existed on the TM segments. Based on the number of transmembrane domains and the residues at metal ion-binding sites, the plant HMA family members were categorized into three subgroups: P1B-1 ATPases, P1B-2 ATPases, and P1B-4 ATPases. Specifically, the P1B-1 ATPase subgroup included the motifs TM4(CPC), TM5(YN[X]₄P), and TM6(M[XX]SS); the P1B-2 ATPase subgroup featured the motifs TM4(CPC), TM5(K), and TM6(DKTGT); the P1B-4 ATPase subgroup contained the motifs TM4(SPC) and TM6(HE[X]GT), all of which were critical for protein functions. Molecular docking results revealed the importance of conserved sequences such as CPC/SPC, DKTGT, and HE[X]GT in metal ion coordination and stabilization. These findings provide potential molecular targets for enhancing Cd uptake and tolerance of O. japonicus by genetic engineering and lay a theoretical foundation for developing new cultivars with high Cd accumulation capacity.
Cadmium/metabolism* ; Adenosine Triphosphatases/metabolism* ; Ophiopogon/drug effects* ; Soil Pollutants/toxicity* ; Plant Proteins/metabolism* ; Stress, Physiological ; Multigene Family ; Gene Expression Regulation, Plant

The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon-intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.
Humans ; Membrane Proteins/genetics* ; Pituitary Neoplasms/genetics* ; Biomarkers

Distraction osteogenesis has been widely used to correct in craniosynostosis in craniofacial surgery since the end of last century because of its advantages such as minimal surgical trauma, short operation time and stable postoperative effect. There are many kinds of distraction osteogenesis procedures for the treatment of craniosynostosis. In order to facilitate patients and surgeons to understand the advantages and disadvantages of these surgical procedures and choose appropriate treatment strategies, the authors reviewed operations of distraction osteogenesis by using internal or external device, and the spring-assisted distraction osteogenesis. Author also evaluated its complications, advantages and disadvantages of these procedures.

Distraction osteogenesis has been widely used to correct in craniosynostosis in craniofacial surgery since the end of last century because of its advantages such as minimal surgical trauma, short operation time and stable postoperative effect. There are many kinds of distraction osteogenesis procedures for the treatment of craniosynostosis. In order to facilitate patients and surgeons to understand the advantages and disadvantages of these surgical procedures and choose appropriate treatment strategies, the authors reviewed operations of distraction osteogenesis by using internal or external device, and the spring-assisted distraction osteogenesis. Author also evaluated its complications, advantages and disadvantages of these procedures.

OBJECTIVE： To investigate the effects of Kangfuxin liquid on repairing cartilage defect model of knee osteoarthritis （KOA） in rabbits and its mechanism. METHODS： Totally 72 male New Zealand rabbits were selected and randomly divided into model control group and Kangfuxin low-dose， medium-dose， high-dose groups， with 18 rabbits in each group. A cartilage defect model of the medial femoral condyle of the right knee joint in rabbits was established by drilling after anesthesia surgery. Then the rabbits in each group were given medicine via articular cavity immediately. Kangfuxin low-dose， middle-dose and high-dose groups were given 20％， 40％， 80％ Kangfuxin liquid； model control group was given constant volume of normal saline consecutively， 0.2 mL/kg， once every 3 days. At 4th， 8th， 12th week after medication， the wound repair of cartilage defect in rabbits was observed. Immediately after medication and at 4th， 8th， 12th week after medication， repaired tissue of cartilage defect in rabbits was scored histologically with Wakitani scoring standard under light microscope. At 12th week after medication， pathological changes of repaired tissue of cartilage defect in rabbits were observed by Masson staining. The levels of NO， SOD and LPO in joint fluid and PYD in urine of rabbits were detected by ELISA. RESULTS： At 4th， 8th， 12th week after medication， compared with model control group， cartilage defects in rabbits were repaired well in Kangfuxin low-dose， medium-dose and high-dose groups. At 4th， 8th， 12th week after medication， compared with immediately after medication and model control group at same time point， histomorphological score of repairing cartilage defect of knee joint in rabbits decreased significantly in Kangfuxin low-dose， medium-dose and high-dose groups （P＜0.05）. At 12th week after medication， compared with model control group， the histopathology degree of cartilage defect of knee joint in rabbits was significantly alleviated in Kangfuxin low-dose， medium-dose and high-dose groups. At 4th， 8th， 12th week after medication， compared with model control group， the levels of NO and LPO in joint fluid and PYD level in urine were decreased to different extent in Kangfuxin low-dose， medium-dose and high-dose groups， while SOD level was increased to different extent； at 12th week after medication， the difference of each index has statistical significance （P＜0.05 or P＜0.01）. CONCLUSIONS： Kangangxin liquid can significantly repair cartilage defect of KOA cartilage defect model rabbits， the mechanism of which may be associated with increasing the expression of SOD and mediating NO-inhibited chondrocyte apoptosis.

BACKGROUND:In comparison with stem cel s from other tissues, adipose-derived stem cel s (ADSCs) are not only abundant and easy to harvest but also have the strong abilities to proliferate and differentiate. These make ADSCS the promising stem cel s in the field of oral tissue regeneration. OBJECTIVE:To summarize the biological features of ADSCs and the development of functions as stem cel s in the oral tissue regeneration. METHODS:We took“adipose-derived stem cel s, oral tissue regeneration, bone tissue engineering, periodontal tissue regeneration, bone defects”as the key words in Chinese and English, respectively, to retrieve the related literatures from PubMed, CNKI, Wangfang databases during 2000 to 2016 based on internet search. RESULTS AND CONCLUSION:In vitro studies on periodontal tissue regeneration have shown that ADSCs can promote the regeneration of bones, fibroblasts, blood vessels around the periodontal area, and improve the healing abilities of injured tissues. In the study of craniofacial bone regeneration, ADSCs can successful y repair massive bone loss due to the surgeries of tumor or accidents. ADSCs have a promising role in the oral tissue regeneration, but further studies wil be required because of the problems of immunogenicity and safety.

OBJECTIVE:To provide reference for standardizing the clinical use of carbapenem antibiotics and controlling drug-resistant bacteria infection. METHODS:The detection of 3 kinds of carbapenems-resistant Gram-negative bacillus in our hospi-tal during 2011-2016 were analyzed retrospectively. The consumption,target cure rate and treatment course of carbapenem antibiot-ics were analyzed statistically. The correlation between detection rate of drug-resistant bacteria with the consumption of carbapenem antibiotics was investigated by Pearson test. RESULTS:During 2011-2016,1222 strains of carbapenems-resistant Acinetobacter bauman (CRAB),655 strains of carbapenems-resistant Pseudomonas aeruginosa (CRPA) and 53 strains of carbapenem-resistant Escherichia coli (CRE) were detected in our hospital. The detection rates increased from 23.88%,8.92%,0.09% in 2011 to 80.34%,35.74%,0.97% in 2016. The types of carbapenem antibiotics in our hospital were mainly imipenem and meropenem. The consumption of them increased from 4222,145 g in 2011 to 7218,4387 g in 2016. The both target cure rates were all lower than 60%,and the proportion of the patients with treatment course >14 d was more than 65%. The detection rates of CRAB,CR-PA and CRE were positively correlated with the consumption of carbapenem antibiotics (r>0.9,P<0.05). CONCLUSIONS:The detection rate of carbapenems-resistant Gram-negative bacillus and drug consumption increase year by year in our hospital,and they have certain correlation. The target cure rate of carbapenem antibiotics in our hospital is in low level,and there is a long treatment course. They are should be standardized in the clinic. The selection of carbapenem antibiotics should be strictly followed clinical in-dications so as to reduce the generation of drug-resistant strains.

Aim To investigate the effect of curcumin on radiosensitivity of radioresistant nasopharyngeal carcinoma cell line CNE-2R and its mechanism.Methods The concentration of curcumin was screened by MTT assay.Dose-survival curves were obtained according to the colony forming test for L-Q matching and multitarget-single hitting matching,while SF2 and the correlation parameters of radiation biology were calculated.The changes of cell cycle in CNE-2R cells caused by curcumin were also tested by flow cytometry(FCM).The differential expression of genes related to cell cycle and DNA damage repair were detected by RT-qPCR.Results CNE-2R cells could not be inhibited by 10 μmol·L-1 curcumin.Dealt with 10 μmol·L-1 curcumin for 24 h,the value of α/β increased to 1 596 from 6.56;the value of SF2 decreased to 0.361 Gy from 1.93 Gy;the value of N decreased to 1.06 from 1.60;the value of D0 decreased to 2.12 from 3.27;the value of Dq decreased to 0.12 from 1.53.FCM showed that the cells in G2 phase had a significant increase and the cells in S phase had a significant decrease after dealt with 10 μmol·L-1 curcumin for 24 h.The expression of CDK4 was significantly up-regulated and GADD45g,BRCA1 were significantly down-regulated.Conclusion Curcumin radiosensitizes nasopharyngeal carcinoma cell line CNE-2R by changing cell cycle and affecting DNA damage repair through regulating the expression of CDK4,GADD45 g and BRCA1.

Objective:To investigate the effects of icaritin(ICT)on the proliferation and osteogenic differentiation of rat bone mar-row stromal cells(rBMSCs).Methods:rBMSCs were cultured from the bone marrow of SD rats and identified by multilineage differ-entiation assays.3,6 and 9 days after the treatment of rBMSCs of passage 4 by ICT at 1 0 -9 ,1 0 -8 ,1 0 -7 ,1 0 -6 and 1 0 -5 mol/L re-spectively,the proliferation and differentiation of the cells were examined by cck-8 and alkaline phosphatase (ALP)activity assay kit respectively.The calcium nodule formation was observed by alizarin red(AR)staining 21 days after 1 0 -9 mol/L ICT treatment. Results:Primary rBMSCs showed the typical spindle-like shape with attachment growth.rBMSCs could be induced to osteogenic and adipogenic differentiation.The proliferation of rBMSCs was inhibited but ALP activity was enhanced by ICT.1 0 -9 mol/L ICT in-cresed calcium nodule formation.Conclusion:ICT can dose-dependently inhibit the proliferation,but promote the osteogenic differ-entiation of rBMSCs.