Objective To detect DNA lesions induced by complex pollutants existing in environment using the technique of randomized terminal linker,dependent PCR (RDPCR). Methods SD rats were treated with organic concentrate by injection i.p., DNA were extracted from rat's liver, kidney, lung and leucocytes, then RDPCR was used to detect DNA damage of exon 7 of p53 gene. Results Organic concentrate of drinking water could make rat's genomic DNA broken. Hybridization bands were found in liver and kidney tissues after RDPCR, none in blood and lung tissues. Conclusion Organic concentrate of drinking water can cause the DNA lesions of exon 7 of p53 gene and the major target organs are liver and kidney. The technique of RDPCR can be used to detect DNA damage induced by complex environmental pollutants.

Objective To investigate the protection of Liuwei Dihuang Jiawei Capsula(LDJ Capsula,Rehmanniae Capsula of Six Ingredients) on diabetic nephropathy(DN) rats′ kidney and effect on renal protein kinase C(PKC) activity and connective tissue growth factor(CTGF) of DN rats.Methods The DN rat models were induced by ip injection of streptozotocin(STZ).The rats were randomly divided into five groups: control group; DN model group;Lotensin group;LDJ Capsula group;and Lotensis and LDJ Capsula combination group.Drug intervention term was 12 weeks.Renal ultrastructure was observed by transmission electron microscope and Masson staining.Relative kidney weight,blood glucose level,serum and urine creatinine content,creatinine clearance,excretion rate of the 24 hour urine protein,renal PKC activity,and CTGF expression in renal cortex were measured by immunohistochemistry.Results Deposition of collagen in renal of DN rats was conspicuous.Relative kidney weight,blood glucose level,serum and urine creatinine content,creatinine clearance,excretion rate of 24 h urine protein,renal PKC activity and CTGF expression of DN rats increased obviously.All Lotensin,LDJ Capsula,and the combination of these two drugs could decrease renal PKC activity and CTGF expression and ameliorate proteinuria and renal function of DN rats.At the same time they all could abate the deposition of collagen in renal of DN rats.Combination of these two drugs could decrease renal PKC activity and CTGF expression more ob-viously and at the same time had more notable protective effect on kidney of DN rats.Conclusion All Lotensin,LDJ Capsula,and the combination of these two drugs could protect kidney of DN rats.The combination of these two drugs has more obviously protective effect than using Lotensin only.

AIM: Although the evidence indicates that extracellular matrix metalloproteinase inducer (EMMPRIN) is closely associated with matrix metalloproteinase (MMP) expression in tumor cells, tumor invasion and metastasis, no direct proof that EMMPRIN regulates MMPs in monocytes, especially in the atherogenic milieu is observed. Here we tested this hypothesis by examining MMP-9 expression in macrophages/foam cells and monocyte migration through EMMPRIN knockdown by siRNA. METHODS: The methods of qPCR and Western blotting were used to detect the suppressions of EMMPRIN mRNA and protein expression in macrophages and foam cells transfected with EMMPRIN-specific siRNA. The protein expression of MMP-9 in macrophages and foam cells was also determined. Monocyte migration after EMMPRIN knockdown was observed by a Transwell assay. RESULTS: EMMPRIN knockdown by siRNA markedly abolished the MMP-9 expression by 50% and 40% in macrophages and foam cells, respectively. Migration induced by chemotactic factor MCP-1 and VEGF was significantly attenuated (P<0.05) in monocytes treated with EMMPRIN-siRNA. CONCLUSION: The protein expression and secretion of MMP-9 are down-regulated by EMMPRIN knockdown during monocyte differentiation into macrophages and foam cells. Moreover, EMMPRIN siRNA treatment also prevents monocyte migration. Thus, EMMPRIN plays a key regulatory role for MMP activity and monocyte migration, making it a potential target for pharmacological intervention of atherosclerosis.

Excess energy has become a main reason for increasingly serious human health hazards. Excess energy, mainly ectopically deposits in the liver, pancreas and other organs in the form of triglycerides, and produces chronic oxidative, nitrosative stress (ONS) , and fat toxicity, resulting in insulin resistance and impaired insulin secretion, and further impaired glucose regulation (Pidan). By combining Chinese medical pathogeneses and symptoms analyses, authors found this process has features of Gan disease transferring to Pi. Based on a number of related guidelines and clinical practice, we demonstrated treating sputum and stasis by the same method was one treatment method for intervening liver disease transferring to spleen in metabolic diseases. This idea helps to organic integrating prevention and treatment of major metabolic diseases including non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus, which can improve clinical effectiveness and efficiency of Chinese medicine.
Diabetes Mellitus, Type 2 ; therapy ; Early Intervention (Education) ; Humans ; Insulin ; Insulin Resistance ; Metabolic Diseases ; Non-alcoholic Fatty Liver Disease ; Risk Factors ; Triglycerides

Objective To explore the diagnostic value of LUNX gene to marrow micrometastases of lung cancer.Methods To detect LUNX mRNA of marrow samples of 51 patients of lung cancer,4 patients of breast cancer,6 patients of lymphadenoma,3 patients of liver cancer and 22 patients of benign disease by real-time RT-PCR.Results The positive detection rate and meso-copies of lung cancer were 58.8% (30/51) and 35copies/ml respectively.The positive detection rate and meso-copies of other diseases were all 0,The positive detection rate and meso-copies of lung cancer was significantly higher than that of patients with other diseases (x~2=11.12,U_c=3.7329,P

It is to observe the therapeutic action of Guizhi Fuling capsule and the combination of active ingredients on model rats with uterine leiomyoma. The hysteromyoma rats models was established in rats by loading eatrogen, to observe the effect on pathological condition of uterus, uterus wet weight, the content of estradiol and progesterone. Guizhi Fuling capsule and the combination of active ingredients remarkably decreased uterus weight, restrained the excess proliferation of the smooth muscle of uterus, decreased the estraiol and progesterone in blood serum. Guizhi Fuling capsule and the combination of active ingredients can restrain the formation of hysteromyoma in a dose-dependent manner. Perhaps the combination of active ingredients is the material foundation of antihysteromyoma.
Animals ; Capsules ; Drugs, Chinese Herbal ; therapeutic use ; Estradiol ; blood ; Female ; Leiomyoma ; blood ; drug therapy ; pathology ; Progesterone ; blood ; Rats ; Rats, Wistar ; Uterine Neoplasms ; blood ; drug therapy ; pathology

Seven terpenoids and three sterols were isolated from the methanol extracts of the aerial parts of Ricinus communis by chromatography methods and their structures were identified by spectra analysis as ficusic acid( 1), phytol(2), callyspinol(3) , lupeol(4), 30-norlupan-3beta-ol-20-one(5) , lup-20(29)-en-3beta,15alpha-diol(6) , acetylaleuritolic acid( 7), stigmast4-en-3-one(8) , stig-mast-4-en-6beta-ol-3-one(9) , and stigmast4-en-3,6-dione(10). Compounds 1-3 and 5-10 were obtained from this species for the first time and 5 and 6 showed significant inhibitive activity and good selectivity against 11beta-HSD of mouse and human in vitro. [Key words] Ricinus communis; terpenoids; sterols; 11beta-HSD
11-beta-Hydroxysteroid Dehydrogenase Type 1 ; antagonists & inhibitors ; 11-beta-Hydroxysteroid Dehydrogenase Type 2 ; antagonists & inhibitors ; Animals ; Diabetes Mellitus ; drug therapy ; enzymology ; Humans ; Hypoglycemic Agents ; pharmacology ; therapeutic use ; Inhibitory Concentration 50 ; Mice ; Ricinus ; chemistry ; Sterols ; pharmacology ; therapeutic use ; Terpenes ; pharmacology ; therapeutic use

Animals ; Dose-Response Relationship, Drug ; Hydroxylamine ; toxicity ; Male ; Rats ; Rats, Wistar ; Spermatozoa ; drug effects ; Testis ; cytology ; drug effects

The effects of Wumeiwan (WMW) on TNF-alpha, IL-6, IL-8, IL-10 and NF-kappaBp65 in rats with ulcerative colitis (UC) were investigated, the curative effectiveness of WMW vs salicylazosulfapyridine (SASP) was compared, and the action mechanism was analyzed. Fifty-Six Sprague-Dawley (SD) rats were randomly divided into four groups (n=14 in each group, with equal ratio of male and female): normal control group, model group, SASP group, and WMW group. Except normal control group, the rat UC models in the remaining three groups were established using the method of 2.4-dinitrochlorobenzene (DNCB) immunization and acetic acid local enema. The rats in model group, SASP group, and WMW group were treated with distilled water, SASP, and WMW respectively. The changes in the symptoms and signs were observed, and levels of IL-6, IL-8, TNF-alpha, IL-10 and the expression of NF-kappaBp65 in the colonic tissues were statistically analyzed. The results showed that the levels of IL-6, IL-8, and TNF-alpha were significantly increased (P<0.01), while those of IL-10 significantly reduced (P<0.01) after establishment of rat UC models as compared with normal control group. The levels of IL-6, IL-8, and TNF-alpha were obviously lower, but the level of IL-10 was obviously higher in WMW and SASP groups than those in model group (P<0.05). The levels of IL-6, IL-8, and TNF-alpha were lower, while the level of IL-10 was higher in WMW group than in SASP group. NF-kappaBp65 was expressed negatively or weakly in normal colonic tissues. The positive expression rate of NF-kappaBp65 in WMW group and SASP group was obviously lower than in model group (P<0.01), and there was significant difference between WMW group and SASP group (P<0.05). It was concluded that rat UC model was established successfully. WMW could up-regulate the expression of IL-10, down-regulate the expression of TNF-alpha, IL-6, IL-8, and inhibit the NF-kappaBp65 activity to adjust immune function, indicating WMW had better curative effects on UC in rats.

We designed and synthesized eighteen lycorine derivatives with five different structural types, and evaluated their antiviral activities on a HCoV-OC43-infected H460 cell model. Structure-activity relationships suggested that the introduction of appropriate substituents on the 6N atom of lycorine was beneficial to activity. Compound 6a gave a good activity with the half effective concentration (EC₅₀) and selectivity index (SI) values of 2.36 μmol·L^-1 and 16.52, respectively. Surface plasmon resonance (SPR) result indicated that 6a might target the non-structural protein 12 (NSP12) subunit in RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 with the dissociation constant (K_D) value of 1.36 μmol·L^-1. Molecular docking indicated that 6a might act on nidovirus RdRp-associated nucleotidyltransferase (NiRAN) catalytic center of NSP12, distinct from the mechanism of nucleoside-like drugs such as remdesivir. This study provides scientific data for the development of lycorine derivatives into a new class of anti-SARS-CoV-2 small molecule inhibitors.