This study was aimed to preliminarily evaluate the acute toxicity and anti-inflammatory effects of coffee residue extract. The test maximum tolerated dose was applied in mice by gavage to observe the acute toxicity of coffee residue extract. Mice acute inflammation model was induced by xylene and glacial acetic acid. The gavage administration of coffee residue extract (1.00, 2.00, 3.00 g?kg-1, in terms of crude drug) was given 7 days con-tinuously. The ear swelling rate and celiac capillary permeability were measured. The results showed that the ex-tract of coffee residue maximum tolerated dose in mice is 8 . 60 g?kg -1 ( in terms of crude drug ) . The coffee residue extract of 3 . 00 g?kg-1 is able to inhibit ear swelling induced by xylene in mice ( P < 0 . 05 ) and the ex-cessive celiac capillary permeability ( P < 0 . 05 ) . It was concluded that the coffee residue extract have certain an-ti-inflammation activities.

Alpinia officinarum Hance of the Chinese traditional herb for the treatment of emesis,abdominal pain and diarrhea has been used to counteract gastric disease induced by indomethacin in rats without obvious side effects.However,the role of herb-drug interaction between indomethacin and A.officinarum based on pharmacokinetic,tissue distribution and excretion still remains unknown.In this study,an ultra-fast liquid-tandem mass spectrometry(UFLC-MS/MS)method was developed for simultaneous determina-tion of indomethacin and its three metabolites,O-desmethylindomethacin(ODI),deschlor-obenzoylindomethacin(NDI)and indomethacin acyl-β-D-glucuronide(IDAβG)by oral administration of indomethacin solution with and without the ethanolic extract of A.officinarum and applied to comparative pharmacokinetic,tissue distribution and excretion studies.Our results clarified that oral administration of A.officinarum produced significant alterations in the pharmacokinetic parameters of indomethacin.And the pharmacokinetic interaction between indomethacin and A.officinarum reduced the systemic exposure of indomethacin and increased its elimination.Tissue distribution results demonstrated that co-administration of A.Officinarum could not reduce the accumulation of indo-methacin in the target tissue of the stomach,but could accelerate the excretions of indomethacin and its three metabolites including ODI,NDI and IDAβG in the bile and feces of rats in the excretion study.Therefore,A.Officinarum might have a gastrointestinal protective effect through the interaction role with indomethacin based on the pharmacokinetics and excretion in rats.

[Abstract] Objective: To investigate whether AP1903, a small-molecule chemical inducer, can terminate the cytotoxicity of CD19CAR-T cells over-expressing iCasp9 suicide gene in vivo and in vitro. Methods: CD19CAR-T cells over-expressing iCasp9 (iCasp9-CD19CAR-T) were constructed and co-incubated with AP1903. Then, the cell phenotype and apoptosis were detected by Flow cytometry, and the iCasp9/CID suicide gene system was verified on K562 and T cells, respectively. The cytotoxicity of iCasp9-CD19CAR-T cells was detected in vivo (survival rate of NCG mice bearing Raji cell transplanted xenograft) and in vitro (cell killing function was detected by Flow cytometry) under the administration of AP1903. Results: Compared with CD19CAR-T cells, iCasp9-CD19CAR-T cells showed in significant difference in proliferation, phenotype and cytotoxicity both in vitro and in vivo (all P>0.05). At 2 h after AP1903 administration, the apoptosis rates of K562 and T cells co-expressing iCasp9 and CD19CAR were (33.8±0.9)% and (27.95±0.35)%, respectively; and at 24 h after AP1903 administration, the apoptosis rates reached 100% in both cell lines. The in vitro cytotoxicity of iCasp9-CD19CAR-T cells induced by AP1903 was significantly lower than that without AP1903 treatment (P<0.01); the 60-day survival rate of mice bearing Raji cell transplanted tumor treated with AP1903-induced iCasp9-CD19CAR-T cells was also significantly lower than those treated with iCasp9-CD19CAR-T cells alone (P<0.01). Conclusion: AP1903 can effectively terminate the cytotoxicity of CD19CAR-T cells over-expressing iCasp9 suicide gene in vitro and in vivo.

Objective To explore the value of T2*mapping in quantitatively evaluate changes in knee joint cartilage and subchon-dral bone of new recruits before and after intensive training.Methods MRI scans of the right knee joint were performed three times on 20 new recruits:before intensive training,after one week of intensive training,and after one month of rest.The knee joint cartilage was divided into six regions:lateral femur(LF),medial femur(MF),lateral tibia(LT),medial tibia(MT),patella cartilage(PC),and trochlea cartilage(TC).Using the posterior angle of the meniscus as a boundary,LF and MF were divided into the cLF/cMF and pLF/pMF.Divid-ed into superficial zone(SZ)cartilage and deep zone(DZ)cartilage based on a thickness of 1/2 of the cartilage.The subchondral bone was divided into superficial bone(SB)within 5 mm of the joint cartilage,and deep bone(DB)within 6-10 mm of the joint cartilage.The T2*values of each region of cartilage and subchondral bone were evaluated through region of interest(ROI)analysis.Single fac-tor analysis of variance was used to compare the changes in T2*values.The LSD test method was used for inter-group comparison.Results After one week of intensive training,MT-SZ,cMF-SZ,PC-SZ,TC-SZ were significantly higher than before intensive training(P＜0.05).After one month of rest,there was no statistically significant difference in the T2*value of the cartilage area compared with before intensive training(P＞0.05).There was a trend of"rising first and then falling".There was no statistically signifi-cant difference in the T2*value of subchondral bone of the knee joint before intensive training and after one week of intensive training(P＞0.05).Compared with after one month of rest,except for cLF-DB,pLF-DB,trochlea cartilage-deep bone(TC-DB),the T2*value of the subchondral bone of the remaining knee joint increased before intensive training and after one week of intensive training,with sta-tistically significant differences(P＜0.05).Conclusion T2*mapping can display the changes in the ultrastructure and biochemical components of joint cartilage and subchondral bone after the new recruits intensive training,detect early injuries and conduct non-invasive quantitative evaluation.

The hinge structure, also known as hinge region or bend, is a special structure found in some antimicrobial peptides. Most studies on antimicrobial peptides focused on the standard secondary structure of α-helix and β-sheet, while the hinge structure and its functions were rarely studied. The hinge structure confers the antimicrobial peptides an improved structural flexibility, which may promote their disruptive effect on bacterial membrane or their binding efficiency to the intracellular targets, thus resulting in a higher antibacterial activity. Meanwhile, the hinge structure may reduce the structural rigidity, which may eliminate the cytotoxicity of antimicrobial peptides to eukaryotic cells. This article reviews the structural characteristics of the hinge structure, its effects on the biological activity of antimicrobial peptides and application in the molecular design, with the aim to provide a reference for the design and development of new antimicrobial peptides.
Anti-Bacterial Agents/pharmacology* ; Anti-Infective Agents/pharmacology* ; Antimicrobial Cationic Peptides/pharmacology* ; Pore Forming Cytotoxic Proteins ; Protein Structure, Secondary

OBJECTIVE：To establish a method for the determination of aloesin in plasma of rats ，and to investigate pharmacokinetic characteristics of aloesin. METHODS ：The plasma samples were precipitated with methanol. Using aloeresin D as internal standard ，the plasma concentration of aloesin was determined by LC-MS/MS. The determination was performed on Synergi Hydro-RP column with mobile phase consisted of 0.1‰ formic acid-methanol （gradient elution ）at the flow rate of 0.50 mL/min. The column temperature was 30 ℃，and sample size was 5 µL. The electrospray ionization source was applied to carry out negative ion detection with multiple reaction monitoring mode . The ion transitions for quantitative analysis were m/z 393.1→272.9（aloesin） and m/z 555.3→144.9（internal standard ），respectively. The concentration of aloesin in venous blood was determined by above method at 0.083，0.167，0.333，0.667，1，1.5，2.5，4，6，8，10 h after intravenous injection （3.35 mg/kg）and intragastric administration（16.75 mg/kg）of aloesin. DAS 3.0 software was used to calculate pharmacokinetic parameters. RESULTS ：The linear range of aloesin were 1-600 ng/mL（r＝0.994 5）. The lower limit of quantification was 1 ng/mL，and RSDs of within and between batches were less than 15％；accuracies within and between batches were within ±15％. The matrix factors were （92.74± 4.33）％-（94.84±2.57）％，and extraction recoveries were （69.04±2.13）％-（75.03±2.84）％；the deviation between the measured results of the stability test and the theoretical values were within ±15％. After intravenous injection and intragastric administration of aloesin ，main pharmacokinetic parameters were as follows ：cmax were（10 693.3±2 745.3）and（223.3±36.2）ng/mL；t1/2 were （2.45±1.45）and（3.33±1.91）h；AUC0－24h were（4 190.6±883.6）and（1 210.1±93.9）ng·h/mL（n＝3）. Absolute bioavailabi- lity was 11.13％. CONCLUSIONS ：The established method is rapid and sensitive for plasma determination of aloesin ，and suitable for its pharmacokinetic study.