Natural medicines (NMs) are indispensable sources for the development of modern drugs. However, the targets for most natural compounds are unknown and the current pharmacokinetic evaluation systems developed for target- defined drugs may not be directly applicable to NM- based drug discovery, which is a major bottleneck in bringing natural compounds to the clinic. We propose the concept of ″ reverse pharmacokinetics″ and discuss how a ″ reverse pharmacokinetics″ perspective could help clarify key questions in modern drug discovery from NMs with validated clinical benefits, thereby strengthening the translational potential. Reverse pharmacokinetics can provide physiologically relevant clues to the target identification and mechanistic study of NMs, which may also innovate drug discovery for complex diseases. We anticipate that an evolving deep understanding of the novel mode of action of natural compounds with a reverse pharmacokinetic insight may improve discovery of both single ingredient and multiple-component modern drugs from NMs.

Wnt/β-catenin signaling pathway plays an important role in the proliferation, growth, invasion, and metastasis of human cancers. Moreover, β-catenin/T-cell factor 4 (TCF4) interaction regulates the transcription of the key oncogenes in Wnt/β-catenin signaling pathway. Therefore, β-catenin/TCF4 interaction would be a promising therapeutic target for the development of highly selective anticancer agents. At present, most ongoing small-molecule inhibitors targeting β-catenin/TCF4 interaction, including PKF222-815, iCRT3/5/14, LF3, and sanguinarine, have been developed in preclinical studies for human cancer therapeutics. In this review, we summarized the research advances of up-to date inhibitors targeting β-catenin/TCF4 interaction, including the molecular structure and cellular functions of β-catenin in canonical Wnt signaling pathway. This review holds a hopeful avenue for the development of novel and highly selective Wnt inhibitors targeting β-catenin/TCF4 interaction for future anticancer strategy.

Objective To further investigated the effect of minocycline on the inhibition of microglial activation and subsequent protection of nigral DA neuron.Methods 20 rats injected with LPS in the substantia nigra (SN) were randomly divided into two groups (LPS group and LPS+Minocycline group).The behavior was observed on the 7~(th) d and 14~(th) d.The immunohistoehemistry,in situ hybridization and Western-blot were used to detect the levels of positive neuron,mRNA,protein of TH and OX-42. Results The slightly rotational behavior was observed in LPS+Minoeyeline group.The majority of mieroglias were activated in the two groups.Some microglia in the SNpc remained ramified in LPS+ Minocycline group.The numbers of hypertophie microglia in LPS+Minoeyeline group were less than that in LPS group.Western-blot showed that the protein of OX-42 in two LPS groups was higher than in normal group(P

The pharmacokinetic research of traditional Chinese medicines (TMC) is an inalienable part of the chain of TCM modernization and plays an important role in the TCM novel drug development. However, the researching method and system that is consistent with the specific characteristics of TCM, i.e., multiple-components and targets, is still lacking. Furthermore, the current understanding of the critical scientific questions of TCM pharmacokinetics remains still unclear. This review makes a brief summary of our recent developments on the pharmacokinetic exploration of TCMs, mainly including integral pharmacokinetic study of multiple components, herbalome analysis both in vitro and in vivo, mechanism based compatibility study for herbal components interactions, and the representative pharmacokinetic study for single herbal compound. Furthermore, the critical scientific questions of TCM pharmacokinetics are discussed based on understanding the requirements of novel drug developments from TCM.
Animals ; Drug Combinations ; Drug Interactions ; Drug Synergism ; Drugs, Chinese Herbal ; isolation & purification ; pharmacokinetics ; Humans ; Medicine, Chinese Traditional ; Plants, Medicinal ; chemistry ; Principal Component Analysis ; Quantitative Structure-Activity Relationship

AIM: This study was designed to explore the effects of short-term and long-term pretreatment of diammonium glycyrrhizinate (GLN) on the pharmacokinetics of entecavir (ETV) in rats. METHODS: Male SD rats were randomized into short-term and long-term experimental groups, respectively. In the short-term experiment, the control group received saline, the low dose group received GLN 13.5 mg·kg(-1) and the high dose group received GLN 40.5 mg·kg(-1). ETV (0.09 mg·kg(-1)) was given i.g. 0.5 h after saline/GLN administration. For the long-term experiment, rats were allocated into two experimental designs. The control group received saline/ETV (0.09 mg·kg(-1)), the low dose group received GLN 13.5 mg·kg(-1)/ETV 0.09 mg·kg(-1) + GLN 13.5 mg·kg(-1), while the high dose group received GLN 40.5 mg·kg(-1)/ETV 0.09 mg·kg(-1) + GLN 40.5 mg·kg(-1); all administration was continued for 15 days. On the 16(th) day, 0.09 mg·kg(-1) ETV was administrated to all groups. Blood samples were obtained at different time points after ETV administration to determine plasma ETV concentrations. RESULTS: Pretreatment with glycyrrhizin resulted in no significant alterations in the main pharmacokinetic parameters of ETV in the short-term and long-term administration experiments. CONCLUSION Diammonium glycyrrhizinate has no effect on ETV pharmacokinetics in rats.
Animals ; Drug Interactions ; Glycyrrhizic Acid ; pharmacology ; Guanine ; analogs & derivatives ; blood ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the immunogenetic features of human leukocyte antigen DRB1, DQB1 locus and children with Helicobacter pylori (H. pylori) infection in Han ethnic population in Kunming and its association with digestive diseases and H. pylori to better understand the immunogenetic features of the H. pylori infection.

METHODSPolymerase chain reaction-sequence specific primer (PCR-SSP) method was used to study the HLA-DRB1, DQB1 allelic frequency distribution on 35 children with H. pylori infection and 37 healthy controls in Han ethnic population in Kunming.

RESULTSAllelic frequencies of HLA-DRB1 * 0901, DQB1 * 03032 in the H. pylori infection group were lower than those of the healthy control group (7.14% vs. 31.08%, chi(2) = 13.16, Pc < 0.012; 5.71% vs. 25.68%, chi(2) = 10.68, Pc = 0.007) but the rest alleles' frequencies did not show significant differences.

CONCLUSIONThese result suggested that HLA-DRB1 * 0901, DQB1 * 03032 might protect the H. pylori infection in Han ethnic population in Kunming.

Adolescent ; Alleles ; Child ; China ; epidemiology ; ethnology ; Female ; HLA-DQ Antigens ; genetics ; immunology ; HLA-DQ beta-Chains ; HLA-DR Antigens ; genetics ; immunology ; HLA-DRB1 Chains ; Helicobacter Infections ; epidemiology ; genetics ; immunology ; Helicobacter pylori ; Humans ; Male ; Polymerase Chain Reaction

OBJECTIVETo investigate the effects of immunization with fusions of dendritic cells and H22 cells on tumor-bearing mice and their possible mechanisms.

METHODSFusion cells of DC and H22 cells were prepared with polyethylene glycol (PEG). Expression of MHC and costimulatory molecules by dendritomas were determined by FACs. To study the antitumor immune preventative and therapeutic effects, fusions were subcutaneously injected into tumor-bearing mice. The cytotoxic T lymphocyte (CTL) activity was determined by LDH method, the expression of TNF-a and IFN-g in tumors were assayed by RT-PCR.

RESULTSThe data showed that the hybridomas of DC and H22 cells acquired both DC and H22 cell phenotypes. Immunization of BALB/C mice with DC/H22 fusions induced potent CTL activity (mean CTL activity=0.624+/-0.024, compared with DC + H22, DC, H22 groups, F = 65.46) and a protective immunity against a high dose of H22 tumor challenge. After treatment with hybridomas, the survival time of tumor-bearing mice was greatly extended (x2=18.45). The expression levels of TNF-a and IFN-g mRNA were remarkably increased (TNF-a, F = 47.84; IFN-g, F = 37.23).

CONCLUSIONSThe hybridomas of DC and H22 cells could induce effective antitumor immune responses and may have a useful potential in prevention and management of the recurrences and metastases of HCC.

Animals ; Cancer Vaccines ; immunology ; Carcinoma, Hepatocellular ; genetics ; immunology ; Cell Fusion ; Dendritic Cells ; immunology ; Female ; Hybridomas ; Immunization ; Interferon-gamma ; biosynthesis ; genetics ; Liver Neoplasms, Experimental ; genetics ; immunology ; prevention & control ; Mice ; Mice, Inbred BALB C ; Polyethylene Glycols ; T-Lymphocytes, Cytotoxic ; immunology ; Tumor Necrosis Factor-alpha ; biosynthesis ; genetics ; Vaccination

OBJECTIVETo study if there is any association between frequency of HLA-DRB1 and DQB1 genes and susceptibility or resistance to Helicobacter pylori (Hp) infection among children of Yi ethnic group in Kunming for understanding the immunogenetic features of the digestive diseases associated with Hp infection.

METHODSPeripherial blood samples were collected from 156 children of Yi ethnic group in a primary school in Kunming city by cluster sampling and the blood Hp-IgG tests (ELISA) were performed. The samples were divided into two groups (Hp-IgG-positive group and Hp-IgG-negative group) according to the blood Hp-IgG test results. There were 61 children in Hp-IgG-positive group and 95 children in Hp-IgG-negative group. Forty children who were chosen from each group by simple random sampling underwent (13)carbon-urea breath test ((13)C-UBT). Thirty-three children who were Hp-IgG-positive and (13)C-UBT-positive were defined as currently Hp- infected group; 39 children who were Hp-IgG-negative and (13)C-UBT-negative were defined as Hp-non-infected group. DNA specimens were extracted from the lymphocytes of their peripheral blood samples. HLA-DRB1 and DQB1 DNA typing was performed by using polymerase chain reaction with sequence specific primers (PCR-SSP). HLA-DRB1, DQB1 allelic frequency distribution among currently Hp infected and non-infected children was compared.

RESULTSHLA-DRB1 * 12 gene frequency among children in Hp non-infected group was higher than that in the currently Hp-infected group (42.31% vs. 14.52%, P < 0.001, Pc < 0.012); however, HLA-DRB1 * 11 gene frequency in the Hp-non-infected group was lower than that in the currently Hp-infected group (3.85% vs. 12.9%, P < 0.05, Pc > 0.05). HLA-DQB1 * 0301 gene frequency in the Hp non-infected group was higher than that in the currently Hp-infected group (55.13% vs. 32.26%, P < 0.007, Pc < 0.05); however, HLA-DQB1 * 04 gene frequency in the Hp non-infected group was lower than that in currently Hp infected group (2.56% vs. 11.29%, P < 0.05, Pc > 0.05).

CONCLUSIONSHLA-DRB1 * 12 and HLA-DQB1 * 0301 gene may be associated with protection against Hp infection in Kunming Yi ethnic group children. Further studies with larger sample size are needed to clarify if HLA-DRB1 * 11 and HLA-DQB1 * 04 are associated with susceptible gene to Hp infection.

Adolescent ; Child ; China ; ethnology ; Gene Frequency ; Genetic Predisposition to Disease ; HLA-DQ Antigens ; genetics ; HLA-DQ beta-Chains ; HLA-DR Antigens ; genetics ; HLA-DRB1 Chains ; Helicobacter Infections ; ethnology ; genetics ; Helicobacter pylori ; Humans

Objective To discuss the technique and technique-related issues of percutaneous kyphoplasty(PKP).Methods The study involved 69 vertebrae in 51 cases of painful osteoporotic vertebral compressive fractures.Under X-ray fluoroscopy monitoring,the fractured vertebral bodies were treated by kyphonplasty with inflatable balloon.The preoperative and postoperative vertebral height and Cobb angle in radiography were measured and analyzed.Results All patients tolerated the procedure well with dramatic pain relief within 72 hours after the procedure.No clinical complication was found.The loss heights of the anterior and mid portion of the vertebral body reduced from 15?4mm and 11?4mm preoperatively to 10? 4mm and 6?3mm postoperatively,respectively.Cobb angle corrected averagely from 22??6? preoperatively to 12??4?.There was significant difference between preoperative and postoperative measures (P

Objective To evaluate the outcome of health education program on drowning prevention among primary and secondary school children in rural areas. Methods A township was selected and all the students from grade 3 to 5, grade 7 to 8, and grade 10 to 11 were selected to take part in the program. Twelve intervention measures on natural water safety and drowning prevention were carried out for one year. Information was collected using the same questionnaire before and after the intervention program. Results One year after the intervention was carried out, children's knowledge on drowning prevention improved significantly (13.21, 95% CI: 12.51-13.90) , and a positive effect was also noticed among boys (12.77, 95%CI: 11.77-13.77), girls (13.80, 95%CI: 12.82-14.78),and among primary school children (15.51,95%CI: 14.30-16.72), senior high school children (10.78,95%CI: 9.50-12.05) and junior high school children (12.77,95%CI: 11.84-13.71). Overall rates on risk behaviors dropped from 41.4% to 32.2% (by 22.2%) including 15.6% for boys, 35.2% for girls and 13.8%, 29.3%, 26.3% for primary school children, senior high school children, junior high school children, respectively. The incidence rates for non-fatal drowning decreased by 58.9% (from 5.6% to 2.3%). The person-times for treatment on sight, in emergency settings, in outpatient clinic or in the hospitals had a reduction from 399, 78, 36 to 175, 32, 14, respectively. Conclusion Health education program could improve children's perception on water safety, and reduce their risk behaviors as well as on the incidence of non-fatal drowning in the rural areas.