OBJECTIVE To evaluate whether the IDO1 inhibitor 1- methyl- L- tryptophan (1- MT) combine calcium influx inhibitor carboxyamidotriazole (CAI) could further enhance the suppression of programmed death 1 (PD-1) in CD8 + T cells and investigate the curative effect of the combined use. METHODS CD8 +T cells were isolated from normal mice spleen by negative selection using magnetic cell separation. The isolated CD8 +T cells were cultured in RPMI 1640 medium containing 10% FBS and 100 U·mL- 1 IL-2 and activated by the addition of anti-CD3 and anti-CD28 (1 g·L- 1 each mabs). CD8 + T cells were pretreated for 48 h with drug and the fluo- 3 as a marker of intracellular calcium concentration was detected by flow cytometry. The calcineurin (CaN) levels were assayed with ELISA in CD8+T cells after 48 h incubation with 10 μm CAI. The nuclear translocations of NFAT and AHR were detected by immunofluorescent staining after 48 h of drug treatment. The expression of PD-1 in CD8+T cells was analyzed by flow cytometry. RESULTS Intracellular fluorescent intensity was markedly debase due to CAI treatment(P<0.01). Meanwhile, the changes of CaN content had a resembled correlation (P<0.01). Immunofluorescence experiment showed that after combination therapy the transfer of NFAT and AHR in nuclear substantially reduced. Flow cytometry revealed that after the combination caused a significant decrease in PD-1 expression in CD8+T cells. CONCLUSION CAI and 1-MT could inhibit markedly the expression of PD-1 in CD8 +T cells by inhibiting the nuclear translocation of NFAT and AHR, respectively and the combination of them has synergetic effect.

OBJECTIVETo investigate the antitumor effects of koumine in mice bearing H22 solid tumor and its effect on the immune system of the mice.

METHODSThe changes in spleen and tumor weights and blood cell count were observed after koumine treatment in BALB/c athymic mice bearing H22 solid tumor, using normal saline solution and 5-Fu as the controls.

RESULTSKoumine significantly inhibited the tumor growth in a dose-dependent manner. The spleen index and blood cell counts in koumine group showed no significant differences from those in the saline control group, but higher than those in 5-Fu group.

CONCLUSIONKoumine can significantly inhibit the growth of H22 solid tumor without obvious inhibitory effect on the immune system in mice.

Animals ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Female ; Gelsemium ; chemistry ; Indole Alkaloids ; isolation & purification ; therapeutic use ; Liver Neoplasms, Experimental ; drug therapy ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Phytotherapy

OBJECTIVETo observe the modulatory effect of subthalamic nucleus (STN) on activity of motor cortex during exhausting exercise.

METHODSElectrocorticogram (ECoG) and local field potentials (LFPs) recording techniques were applied simultaneously to observe the dynamic changes of oscillations in sensorimotor area and STN of rat during exhausting exercise.

RESULTSRats ran well initiatively with treadmill at the beginning of the exercise, about 45 min (45 +/- 11.5) later, movement capacity reduced. Corresponding electrical property showed that STN activity increased significantly while activity of cortex decreased significantly. Subsequently rats continued exercise with minor external stimulation utill exhaustion. Activity of ECoG reached the minimum under exhausting stations (P < 0.01), while the activity of LFPs changed insignificantly (P > 0.05).

CONCLUSIONDuring the exhausting exercise, the cortex activity was extensively depressed with the development of fatigue, while the activity of STN increased significantly at the early stage of fatigue, STN took part in the modulation of central fatigue through negative induction. And the increase of STN activity may be one of the key measures accounting for protective inhibition.

Animals ; Cerebral Cortex ; physiology ; Electrophysiological Phenomena ; physiology ; Male ; Neurons ; physiology ; Physical Conditioning, Animal ; physiology ; Physical Exertion ; physiology ; Rats ; Rats, Wistar ; Subthalamic Nucleus ; physiology

Objective To evaluate the effects of low dose Ethyl Carbamate (EC)on the immune function of ICR mice and to provide evidences for developing food safety standard.Methods The ICR mice were divided into four groups,and three groups were treated with 0.1 7,0.83,1 .67 mg/kg·bw EC respectively and the control group was treated with distilled water only.The immune function of ICR mice was determined by five aspects,including cellular immunity,humoral immunity,mononuclear macrophages's phagocytosis,natural killer cell activity and the organ coefficients of immune organs. Results Compared with the control group,the 1 .67 mg/kg·bw EC significantly inhibited the proliferation of spleen lymphocyte,natural killer cell activity and the hemolysis plaque -forming ability induced by ConA (P <0.05 ). Conclusion EC can cause the inhibition of normal mouse's immune function.

Objective Toevaluatetheeffectsofwholecranberrypowder(Pacranpowder)onimmunefunctionsofICR miceinvivo.Methods FemaleICRmice(18-22g)wererandomlydividedintocontrolgroupandlow,mediumandhigh dose groups of whole cranberry powder (83,1 66,and 332 mg/kgbw).Whole cranberry powder was treated with by gavage for 30 days continuously.Control mice were treated with distilled water only.Their immune functions were analyzed, including serum hemolysin analysis, antibody -producing cells (APCs ), conA -induced splenic lymphocyte transformation,SRBC-induced delayed type hypersensitivity,natural killer cell activity assay,peritoneal macrophages phagocytosed chicken red blood cells (CRBC),carbon clearance test and thymus or spleen /body weight ratio.Results Ascomparedwiththecontrols,wholecranberrypowdertreatmentincreasedthenumberofplagueformingcells(PFCs)at 83 mg/kgbw group(P<0.05 ).There were no statistical difference in the total production of antibodies,the activity of conA-induced splenic lymphocyte transformation,the left-hind voix pedis thickness,NK cytoactivity,the phagocytosis index and ratio of peritoneal macrophages, the carbon clearance ability between the groups treated with different concentrationsofwholecranberrypowderandthecontrolgroup(P>0.05).Conclusion Wholecranberrypowdercan enhance mouse the number of plague forming cells (PFCs).

Objective To explore the mutagenic effect of sodium pentachlorophenate (NaPCP) on zebrafish p53 gene coding sequence(CDS) in somatic cell.Methods The experiment was carried out using tuebingen strain of zebrafish, according to the results of acute toxicity test to determine the exposure levels in zebrafish.Zebrafish were randomly divided into blank control group and exposed groups, each containing 10 zebrafish.After exposing for 45d of NaPCP, the RNA was extracted from liver of zebra fish, and the p53 gene including a complete coding sequence of was obtained by RT-PCR.Results LC50 of NaPCP was 18.4 μg/L.Sequence analysis showed that the p53 gene CDS length of 1125bp, encoding 374 amino acids.The percent identity between the published zebrafish sequence of p53 (GI:425876786)and ours was 99.2%,with the other biological sequence of p53 existing some differences.After 45d exposure, zebrafish p53 gene of NaPCP exposure group had mutated at the concentration of 1.8 μg /L.The base substitution of GAG→AAG at codon 8,CAT→CAG at codon 148 and CAG→CAA at codon 229 were detected by PCR-directed sequencing.This may result in the Glu→Lys and His→Gln of expressed p53 protein.Conclusion NaPCP is a kind of gene mutation, which can induce the mutation of p53 gene in zebrafish somatic cells, that has the potential mutagenic risk for humans.

Objective To learn the changes of blood lead levels and serum biochemical parameters of the school agechildren from different areas. Methods All research objects, the school age children, were from three different areasrespectively, including a mountainous area (L area), an island area (H area) where there is not history of Pb pollution,and an industry area (N area) in relation to Pb pollution. The morning urine and peripheral venous blood samples werecollected from the school age children. Pb in blood (PbB), δ-aminoaevulinic acid in urine (ALA), Ca2+, BUN, Cr inserum, and Thyroid Stimulating Hormone (TSH), thyroxin (T4), free thyroxin (FT4) levels were detected. ResultsPbB levels [M was 36.0 ppb] of the school age children from N area were significantly higher than that of L area [22.0 ppb] andH area [23.8 ppb]. On the contrary, serum Ca2+ levels of the school age children from N area were significantly lower than thatof L area and H area. Serum T4 of N area was significantly lower than that of L area and H area. Serum FT4 of H area wassignificantly higher than that of L area and N area. And TSH of N area and H area were both obviously lower than that of L area.But all of these thyroxin indexes were in the range of normal values. Conclusion It should be widely concerned that thesignificant elevation of PbB levels may have a negative impact on school age children in the future.

Objective To investigate effects of xylo-oligosaccharides with chitooligosaccharides on alcohol-induced liver injury and immune function in mice. Methods Different doses of chitosan oligosaccharide (0.045 g/kg-0.26 g/kgB.W) and xylo-oligosaccaride (0.055 g/kg-0.32 g/kgB.W) were feed to the mice for 30 days. The mice live-injury model was induced by alcohol. MDA、 GSH、 TG level in liver and T lymphocyte proliferation of spleen cells induced by conA, the antibody-producing cells, and natural killer (NK) activity were detected. Results Compared with the live-injury model group, MDA level of low/middle dose group, TG level of middle dose group and pathological evaluation score of liver steatosis of high dose group in mice liver were decreased because of chitosan oligosaccharide and xylo-oligosaccaride feeding. Compared with the control group, the ability of T lymphocyte proliferation of mouse spleen induced by ConA and the antibody-producing cells were increased in mice of middle and high dose group. The differences had statistical significances (P<0.05) . Conclusion Under this experimental condition, xylo-oligosaccharides in combination with chitooligosaccharides could protect the mice from alcohol-induced liver injury and enhance immune function in spleen of normal mice synergistically.

OBJECTIVETo observe the effect of Chinese herbal medicine for supplementing Shen and strengthening the bone on distal femoral trabecular ultrastructure of male rats subjected to simulated weightlessness.

METHODSFifteen male SD rats were randomized equally into 3 groups, including a control group (group A, in which the rats were allowed free movement) and two simulated weightlessness (via tail suspension) groups (group B and C). The rats in group C were treated with the commercially available Chinese herbal preparation, and those in the other two groups received normal saline at the same dose, for a treatment course of 28 days. Observation of trabeculae was performed with scanning electron microscopy.

RESULTSIn group B, the trabeculae of the femur became thinner, fragile, discontinuous with reduced quantity as compared with those in group A. The rats in group C had greater number of the trabeculae than those in group B. Resorption surface decreased and the collagenous fiber were much more regular in group B.

CONCLUSIONThe Chinese herbal medicine may produce beneficial effect on bone microstructure of rats subjected to simulated weightlessness.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Femur ; drug effects ; physiology ; ultrastructure ; Kidney ; drug effects ; Male ; Microscopy, Electron, Scanning ; Rats ; Rats, Sprague-Dawley ; Weightlessness Simulation

OBJECTIVETo evaluate and analyze the mechanism of Pizhen for the treatment of patients with scapular muscle fasciitis.

METHODSOne hundred and sixteen patients were divided into two groups according to random number table method, 58 cases in the treatment group and 58 cases in the control group. After treatment, 109 patients were followed up, and 7 patients lost follow-up (2 cases in the treatment group and 5 patients in the control group). In the treatment group, there were 15 males and 41 females, with a mean age of (28.02 +/- 4.85) years; the course of disease ranged from 0.25 to 3 years; and the patients were treated by Pizhen once a week,and 2 weeks were one treatment course. In the control group, there were 19 males and 34 females, with a mean age of (27.23 +/- 4.54) years old; the course of disease ranged from 0.25 to 1 year; and the patients were treated by acupuncture massage instrument, 20 minutes at a time,once a day for 2 weeks. Soft tissue displacement and banana area were tested by a soft tissue tension tester, pressure value was measured by pressure measuring instrument, and VAS was recorded by pain visual analog scale record.

RESULTSThere were significant differences in tissue displacement, banana area, pressure value and VAS between two groups before and after treatment. The tissue displacement and pressure value in the treatment group were higher than those in the control group,while banana area and VAS were lower than those in the control group. In the treatment group, 30 patients healed, 13 patients got marked improvement, 12 good and 1 poor;while 16 patients healed, 19 patients got marked improvement,11 good and 7 poor in the control group. The therapeutic effects in the treatment group was better than that in the control group.

CONCLUSIONPizhen is an effective method to treat pain in patients with scapular muscle fasciitis by relaxing tendon of soft tissue around pain point of scapular and relaxing compress and stimulation of nerves.

Acupuncture Points ; Acupuncture Therapy ; instrumentation ; Adult ; Case-Control Studies ; Fasciitis ; therapy ; Female ; Humans ; Male ; Treatment Outcome ; Young Adult