Objective To investigate the effect of pretreatment with U75302,antagonist of leukotriene B4 receptor 1 (BLT1),on cisplatin induced acute kidney injury in mice and its immunoregulatory mechanism.Methods Healthy C57BL/6 mice were randomized into four subgroups:1.healthy control group;2.cisplatin group;3.U75302 control group;4.cisplatin + U75302 group,n=6.Group 2 and 4 received intraperitoneal injection of cisplatin (20 mg/kg) on day 0,group 3 and 4received intraperitoneal injection of U75302 (5 μg/mouse) on day 0 and day 2.Mice were sacrificed on the 3rd day and blood and kidney were collected.Renal function and histological changes were estimated,the infiltration of immune cells were determined by flow cytometry,the level of peroxidase (MPO) in kidney were determined by colorimetry,relative expression of TNF-α,IL-1β,CXCL1,CXCL2 were detected by Real-time PCR.Results Compared with healthy control group,levels of BUN,Scr were higher in cisplatin group with serious tubular structural damage.There were more neutrophils,macrophages,CD4+ T lymphocytes,CD8+ T lymphocytes in kidneys of cisplatin group,the level of MPO and relative expression of TNF-α,IL-1β,CXCL1,CXCL2 were also higher in cisplatin group.Compared with cisplatin group,lower BUN [(17.75±1.80) mmol/L vs (42.6±6.66) mmol/L,P ＜0.05],Scr were found in cisplatin+ U75302 group with less tubular structural damage.Meanwhile,U75302 reduced infiltration of neutrophils [(146±13)×103/g vs (296±66) ×103/g,P ＜ 0.05],macrophages [(245± 13)× 103/g vs (420±78)× 103/g,P ＜ 0.05] in the kidney.Levels of MPO [(1.756±0.283) U/g vs (3.308±0.577) U/g,P＜0.05] and relative expression of TNF-α,IL-1β,CXCL1,CXCL2 were also lower.Conclusions BLT1 antagonist U75302 protects mice against AKI induced by cisplatin,and the mechanism is associated with reduced infiltration of inflammatory cells in kidney and the inhibition of kidney inflammation.

To study the chemical constituents from the bark of Myrica rubra, fourteen compounds were isolated from the methanolic extract using various chromatographic techniques, including silica gel, Sephadex LH-20 and preparative HPLC. Their structures were identified on the basis of chemical properties and spectroscopic data, as 3, 5-dimethoxy-4-hydroxymyricanol (1), myricanol (2), myricanone (3), myricanol 11-sulfate (4), myricitrin (5), quercetin (6), quercetin-3-rhamnoside (7), tamarixol (8), uvaol (9), ursolic acid (10), taraxerol (11), myricadiol (12), β-sitosterol (13) and β-daucosterol (14). Among them, compound 1 is a new compound, named as 3, 5-dimethoxy-4-hydroxymyricanol, compounds 8, 9 were isolated from the genus Myrica for the first time.
Diarylheptanoids ; chemistry ; isolation & purification ; Myrica ; chemistry ; Phytochemicals ; chemistry ; isolation & purification ; Plant Bark ; chemistry

Apoptosis ; drug effects ; Cell Line, Tumor ; Drug Synergism ; Flavanones ; administration & dosage ; pharmacology ; Humans ; Multiple Myeloma ; pathology ; Thalidomide ; administration & dosage ; analogs & derivatives ; pharmacology

Objective: Our purpose was to explore the change regularity of β-glucuronidase (β-G) in body of patients with Non-Hodgkin malignant lymphoma. Methods: β-G was examined synchronously both in the serum and in the tumor tissue of 13 cases patient with Non-Hodgkin malignant lymphoma by using the method of enzymlinked immunsorbent assay (ELISA) and immunohistochemistry separately. Among them, 3 cases were studied by using the immuno electron microscopic technique. Results: β-G was highly expressed both in the serum and tumorous tissue in patients with non-Hodgkin malignant lymphoma and there was obviously difference as compared with the control group (P<0.01). Conclusion: The combined detection with functional and morphological methods to β-G, it may be assistant target to early discovery and early diagnosis of Non-Hodskin malignant lymphoma.

Objective To explore the mechanism of skeletal fluorosis via observation on the expression of bone γ-carboxyglutamic acid-containing protein (BGP) and osteoprotegerin (OPG) in the residents of coal-burning fluorosis regions, and to provide a basical data for further monitoring and evaluating the effects of fluoride-reducing projects. Methods Stratified sampling was applied, the 6 villages of fluorosis were chosen as focusing areas for investigation. The residents of villages underwent clinical examination of the skeletal fluorosis. And according to the degree of skeletal fluorosis, villages were divided into three groups, namely light, moderate and severe villages. Radio-Immunoassay and Enzyme-linked immunosorbent assay were used to check the expression of BGP and OPG in the serum. Results The levels of serum BGP in the severe skeletal fluorosis cases[(6.78±4.43)μg/L] were significantly higher(P<0.05) than those in the normal, moderate and the severe groups [ (3.58±1.53), (3.44±2.66), (3.41±2.20)μg/L], respectively. The expression of OPG in the light, moderate and the severe groups [(1251.55±998.31), (1265.94±931.77), (1560.55±858.07)ng/L] were significantly higher (P<0.05) than those in the normal[(520.81±385.05)ng/L], respectively. The levels of BGP in mixed type[(6.09±2.62)μg/L] were much higher(P<0.05) than no mixed type[(3.97±1.53), (3.20±2.12)μg/L]. The levels of OPG in the osteosclerosis, osteoporesis and mixed type[(1321.63±1017.00), (1205.42±852.22), (1529.01±402.83)ng/L] were significantly higher(P<0.05) than those of the normal, respectively. The levels of OPG in the light villages [(452.06±338.10)ng/L] were significantly lower(P<0.05) than moderate and severe villages[(1266.30±899.14), (1851.80±956.08 )ng/L], respectively. The levels of OPG in the severe villages were significantly higher(P<0.05) than moderate villages. Conclusions It indicates that OPG can be used as an early indicator in coal-burning pollution endemic fluorosis results in biochemical changes in the composition of bone.

Abstract: Objective - - To establish a pre column derivatization high performance liquid chromatography method for detecting Methods dimethyl sulfate (DMS) in workplace air. DMS in workplace air was collected with mercaptopyridine impregnated （ silicone tube. The derivative of DMS and mercaptopyridine was eluted by mobile phase phase A: water, phase B: acetonitrile, ∶ the volume ratio was 40 60) , and separated with a C18 column, then detected with diode array detector and quantitated by a Results - standard curve. The linear range of DMS was 0.17 40.00 mg/L, with the correlation coefficient of 0.999 95. The detection limit and the lower limit of quantitation were 0.05 and 0.17 mg/L respectively. The minimum detection concentration and minimum quantitation concentration were 0.02 and 0.04 mg/m³, respectively (air sample volume of 4.5 L, 1.0 mL sample - - - solution). The average desorption efficiency was 98.40% 102.00%. The within run and between run relative standard deviations - - were 0.61% 3.92% and 1.71% 6.00%, respectively. The samples could be stored at room temperature for at least 14 days. Conclusion This method can be used to detect DMS in workplace air.

Abstract: Nitrobenzene compounds (NBCs) are widely used in the world. It has 40 isomers such as nitrobenzene, dinitrobenzene and nitrotoluene, that are highly toxic and difficult to degrade and can cause harm to human health in different degrees. At pres⁃ ent, there is no unified standard method and occupational exposure limit for the detection of NBCs in the air. In terms of sampling medium, solid adsorption tube is mostly used for trapping vapor state NBCs, and filter membrane and solid adsorption tube are mostly used in series for sampling coexist NBCs in vapor state and aerosol state. In the detection methods, gas chromatography and liquid chromatography are common, and ultraviolet spectrophotometry, Raman spectroscopy, ion migration spectrometry and some other rapid response methods and technologies are also used in the detection of NBCs. In the detection of NBCs by gas chro⁃ matography, capillary column separation is commonly used, and the main detectors are flame ionization detector, electron capture detector and mass spectrometry detector. It is of practical significance to establish a method with high sensitivity, strong practica⁃ bility, convenient operation, and can simultaneously collect and detect a variety of NBCs in different states.

KRAS is one of the most frequently mutated human oncogenes. In spite of mounting efforts on the development of direct or indirect inhibition targeting KRAS, little has been achieved because of insurmountable difficulties, titling KRAS "undruggable". Recently, subtype-specific inhibitors have shown great hope. Some KRAS^G12C inhibitors have entered clinical trials, including adagrasib and sotorasib, and have shown preliminary clinical effectiveness. Experiences from the inhibitors targeting the downstream factors of RAS pathways show that the anticancer activity of these drugs will be limited due to the development of drug resistance. Preclinical studies of KRAS^G12C inhibitors have revealed that the application of these agents might be hampered by the drug resistance issue. The current review aims to describe the current status of KRAS^G12C inhibitors, and discuss the mechanisms underlying KRAS^G12C inhibitor resistance, so as to provide the clues for the combat of drug resistance.

Ampulla of Vater ; Common Bile Duct ; transplantation ; Duodenum ; surgery ; Gastrointestinal Stromal Tumors ; pathology ; surgery ; Humans ; Male ; Middle Aged

AIMTo evaluate the antiproliferative activity of contragestazol (DL111-IT) on the human prostate cancer cell line PC3 in vitro and in vivo and to elucidate its potential molecular mechanisms.

METHODSThe cell killing ability of DL111-IT was measured by the 3-(4,5-dimethylthia-zol,2-yl)-2,5-diphenyltetrazolium bromide (MTT) reagent assay method and the tumor xenograft model. The cell cycle was analyzed by flow cytometry and protein expression, including retinoblastoma (pRb), cyclin-dependent kinase 4 (CDK4) and cyclin D1, was detected by Western blotting.

RESULTSDL111-IT exhibited high efficiency on cell growth inhibition of the human androgen-independent prostate cancer cell line PC3. The drug concentration that yielded 50% cell inhibition (IC50 value) was 9.9 mg/mL. In the PC3 tumor xenograft study, DL111-IT (1.25 mg/kg-20.0 mg/kg) given once a day for 10 days significantly inhibited tumor growth, with the inhibition rate ranging from 21% to 50%. Flow cytometric analysis indicated that DL111-IT could cause G1 arrest in the PC3 cell line, but not apoptosis. DL111-IT enhanced pRb expression and down-regulated CDK4 and cyclin D1 expression, suggesting that cell cycle regulation might contribute to the anticancer property of DL111-IT.

CONCLUSIONDL111-IT inhibits the proliferation of human androgen-independent prostate cancer cell line PC3 in vitro and in vivo by a cell cycle regulation pathway.

Androgens ; pharmacology ; Animals ; Cell Division ; drug effects ; Cell Line, Tumor ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase 4 ; metabolism ; Dose-Response Relationship, Drug ; Female ; G1 Phase ; drug effects ; Humans ; Immunosuppressive Agents ; pharmacology ; In Vitro Techniques ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Prostatic Neoplasms ; drug therapy ; pathology ; Resting Phase, Cell Cycle ; drug effects ; Retinoblastoma Protein ; metabolism ; Transplantation, Heterologous ; Triazoles ; pharmacology