Mechanism of Xiaoyao San in treating non-alcoholic fatty liver disease with liver depression and spleen deficiency: based on bioinformatics, metabolomics and in vivo experiments.

Xiaoyao san (XYS) plays an important role in treatment of non-alcoholic fatty liver disease (NAFLD) with liver stagnation and spleen deficiency, but its specific mechanism is still unclear. This study aimed to investigate the material basis and mechanism by means of network pharmacology, metabolomics, systems biology and molecular docking methods. On this basis, NAFLD rat model with liver stagnation and spleen deficiency was constructed and XYS was used to intervene, and liver histopathology, biochemical detection, enzyme-linked immunosorbent assay, quantitative PCR assay and western blotting were used to further verify the mechanism. Through the above research methods, network pharmacology study showed that there were 94 targets in total for XYS in the treatment of NAFLD. Metabolomics study showed that NAFLD with liver depression and spleen deficiency had a total of 73 differential metabolites. Systems biology found that PTGS2 and PPARG were the core targets; Quercetin, kaempferol, naringenin, beta-sitosterol and stigmasterol were the core active components; AA, cAMP were the core metabolites. And molecular docking showed that the core active components can act well on the key targets. Animal experiments showed that XYS could improve liver histopathology, increase 5HT and NA, decrease INS and FBG, improve blood lipids and liver function, decrease AA, increase cAMP, down-regulate PTGS2, up-regulate PPARG, and decrease PGE2 and 15d-PGJ2. In conclusion, XYS might treat NAFLD with liver depression and spleen deficiency by down-regulating PTGS2, up-regulating PPARG, reducing AA content, increasing cAMP, improving insulin resistance, affecting glucose and lipid metabolism, inhibiting oxidative stress and inflammatory response.Communicated by Ramaswamy H. Sarma.

Network pharmacological results found that XYS might treat NAFLD through multiple targets and multiple pathways. Quercetin and kaempferol were main components of XYS in treatment of NAFLD.System biology research results found that PPARG and PTGS2 were the core targets of XYS in the treatment of NAFLD.Metabolomic results suggest that AA and cAMP were differential metabolites of NAFLD.In vivo animal experiments showed that XYS might treat NAFLD by increasing PPARG and decreasing PTGS2, reducing AA and increasing cAMP to regulate glucose metabolism and lipid metabolism.

Hyperoside protects against cyclophosphamide induced ovarian damage and reduced fertility by suppressing HIF-1α/BNIP3-mediated autophagy.

Ovarian damage and infertility are the main side effects of chemotherapy for women of childbearing age with cancer. The main objective of this study was to investigate the protective effects and mechanisms of hyperoside against cyclophosphamide (Cy) -induced ovarian damage and reduced fertility. This study consists of two parts: in vivo experiments using Cy intraperitoneal injections to simulate clinical chemotherapy sessions and in vitro experiments using 4-HC, a precursor of an activated form of Cy, to intervene in human granulosa-like cell line (KGN). We found that Cy disrupted the estrous cycle in mice, resulting in decreased serum Anti-Mullerian hormone (AMH) levels, loss of primordial follicles, primary follicle and secondary follicle, increased atretic follicles, and diminished ovarian reserve function. Cy prolonged the time between mating and pregnancy in mice and increased the number of absorbed embryos. Western Blot analysis demonstrate that Cy activated key proteins of HIF-1α/BNIP3-associated autophagy both in vivo and in vitro, while in vivo experiments we also found that 4-HC increased KGN cell apoptosis, damaged mitochondrial membrane potential, and activated autophagic flow. Co-treatment with hyperoside diminished follicular depletion of the primordial follicles, decreased follicular atresia, prevented Cy-induced excessive hypoxia and autophagy activation, increased mitochondrial membrane potential, thereby increasing follicular reserve and rescuing fertility in Cy-treated mice. It suggests that HIF-1α/BNIP3-mediated autophagy is an essential mechanism by which Cy impairs ovarian function and fertility in mice, by blocking this activation, hyperoside shows potential as an ovarian protectant that may be capable of preserving fertility in women undergoing chemotherapy.

Mechanism of Phellodendron and Anemarrhena Drug Pair on the Treatment of Liver Cancer Based on Network Pharmacology and Bioinformatics.

Background: This study aims to explore the key targets and signaling pathways of the traditional Chinese medicine Phellodendron and Anemarrhena drug pair (PADP) for the treatment of liver cancer. Methods: Firstly, bioinformatics technology was used to analyze GSE62232 gene chip to obtain the differential genes of liver cancer. A network pharmacology technology was used to find the active components of PADP and their targets. Secondly, the differential genes were imported into STRING database to draw a PPI network, and network topology structure map combined with Cytoscape software. And the R language was used to identify differential gene targets and pathways through GO and KEGG pathway enrichment analysis. In addition, AutoDock Vina was used for molecular docking of core targets and core compounds. Moreover, GEPIA online analysis tool was used to perform survival analysis of the core target genes. Finally, RT-PCR was used to verify the changes of key target genes. CCK-8 assay was performed to detect cell proliferation. Flow cytometry was performed to detect the cell cycle and apoptotic. Transwell invasion assay was performed to detect cell invasion. Results: Firstly, a total of 21,654 genes were obtained. After screening, 1019 differential genes were obtained, including 614 down-regulated genes and 405 up-regulated genes. Furthermore, after screening by ADME standards, 52 active ingredients were obtained, of which 37 were Phellodendron and 15 were Anemarrhena. And a total of 36 differential genes have been identified, including 13 up-regulated genes and 23 down-regulated genes. Moreover, through enrichment analysis, we found that PADP may treat liver cancer through multiple channels and multiple pathways including the p53 signaling pathway, IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway and so on. Secondly, the molecular docking results showed that there was certain affinity between the core compounds and core target genes. In addition, GEPIA online analysis showed that ESR1, AR, CCNB1, CDK1, AKR1C3 and CCNA2 might become potential target genes for the survival and prognosis of PADP for the treatment of liver cancer. Finally, it was found that PADP could up regulate genes ESR1 and AR, down regulate genes CCNB1, CDK1, AKR1C3, and CCNA2. PADP could promote the apoptosis of liver cancer cells, shorten the cell cycle, and inhibit the proliferation and invasion of liver cancer cells. Conclusion: PADP may treat liver cancer through multiple targets, multiple channels, and multiple pathways, thereby suppressing cancer cells and improving the living quality of patients.

Non-Lactobacillus-Dominated Vaginal Microbiota Is Associated With a Tubal Pregnancy in Symptomatic Chinese Women in the Early Stage of Pregnancy: A Nested Case-Control Study.

The features of the vaginal microbiota (VM) community can reflect health status, and they could become new biomarkers for disease diagnosis. During pregnancy, domination of bacteria of the genus Lactobacillus in the VM community is regarded as a keystone because they stabilize the VM by producing antimicrobial compounds and competing adhesion. An altered VM composition provides a marker for adverse pregnancy outcomes. This nested case-control study aimed to characterize the VM in women with a tubal pregnancy (TP) presenting with pain and/or uterine bleeding in early pregnancy. Chinese women with a symptomatic early pregnancy of unknown location were the study cohort. 16S rDNA gene-sequencing of V3-V4 variable regions was done to assess the diversity, structures, taxonomic biomarkers, and classification of the VM community. The primary outcome was the location of the early pregnancy. The VM community in women with a TP showed higher diversity (PD-whole-tree, median: 8.26 vs. 7.08, P = 0.047; Shannon Diversity Index, median: 1.43 vs 0.99, P = 0.03) and showed different structures to those in women with an intrauterine pregnancy (IUP) (R = 0.23, P < 0.01). Bacteria of the genus Lactobacillus were significantly enriched in the IUP group, whereas bacteria of the genera Gardnerella and Prevotella were significantly enriched in the TP group. Lactobacillus abundance could be used to classify the pregnancy location (AUC = 0.81). Non-Lactobacillus-dominated microbiota (≤ 0.85% Lactobacillus) was significantly associated with a TP (adjusted odds ratio: 4.42, 95% confidence interval: 1.33 to 14.71, P = 0.02). In conclusion, among women with a symptomatic early pregnancy, a higher diversity and lower abundance of Lactobacillus in the VM is associated with a TP.

MicroRNAs and angiogenesis: a new era for the management of colorectal cancer.

MicroRNAs (miRNAs) are a class of small noncoding RNA molecules containing only 20-22 nucleotides. MiRNAs play a role in gene silencing and translation suppression by targeting and binding to mRNA. Proper control of miRNA expression is very important for maintaining a normal physiological environment because miRNAs can affect most cellular pathways, including cell cycle checkpoint, cell proliferation, and apoptosis pathways, and have a wide range of target genes. With these properties, miRNAs can modulate multiple signalling pathways involved in cancer development, such as cell proliferation, apoptosis, and migration pathways. MiRNAs that activate or inhibit the molecular pathway related to tumour angiogenesis are common topics of research. Angiogenesis promotes tumorigenesis and metastasis by providing oxygen and diffusible nutrients and releasing proangiogenic factors and is one of the hallmarks of tumour progression. CRC is one of the most common tumours, and metastasis has always been a difficult issue in its treatment. Although comprehensive treatments, such as surgery, radiotherapy, chemotherapy, and targeted therapy, have prolonged the survival of CRC patients, the overall response is not optimistic. Therefore, there is an urgent need to find new therapeutic targets to improve CRC treatment. In a series of recent reports, miRNAs have been shown to bidirectionally regulate angiogenesis in colorectal cancer. Many miRNAs can directly act on VEGF or inhibit angiogenesis through other pathways (HIF-1a, PI3K/AKT, etc.), while some miRNAs, specifically many exosomal miRNAs, are capable of promoting CRC angiogenesis. Understanding the mechanism of action of miRNAs in angiogenesis is of great significance for finding new targets for the treatment of tumour angiogenesis. Deciphering the exact role of specific miRNAs in angiogenesis is a challenge due to the high complexity of their actions. Here, we describe the latest advances in the understanding of miRNAs and their corresponding targets that play a role in CRC angiogenesis and discuss possible miRNA-based therapeutic strategies.

Association Between Vaginal Gardnerella and Tubal Pregnancy in Women With Symptomatic Early Pregnancies in China: A Nested Case-Control Study.

The early diagnosis and treatment of ectopic pregnancy (EP) remains a major challenge. Despite a known link between vaginal microbiota and female reproductive health, few studies have focused on the association between vaginal microbiota and pregnancy location. This nested case-control study aimed to characterize the vaginal microbiota in tubal pregnancy (TP) among symptomatic women in early pregnancy. Women with symptomatic early pregnancy of unknown location (PUL) were included in this study. 16S rDNA gene sequencing was performed to assess vaginal microbial diversity and relative abundance. Machine learning and multivariate logistic regression were also used to evaluate the association between Gardnerella and TP. The results indicate that the vaginal microbiome in TP was more diverse (Shannon, p < 0.05) and was different in composition to that of women with intrauterine pregnancy (IUP) (weighted Unifrac, R = 0.08, p = 0.01). The genus Gardnerella was significantly enriched in TP. The XGBoost analysis was able to classify Gardnerella-induced TP more reliably (AUC = 0.621). Moreover, after adjusting potential confounders, our results indicate a robust association between Gardnerella and TP (as a continuous variable, adjusted OR: 12.0, 95% CI: 2.1-67.4, p < 0.01; as a categorical variable (≥0.85%), and adjusted OR: 4.2, 95% CI: 2.0-8.8, p < 0.01). In conclusion, we found that higher virginal Gardnerella levels were associated with TP in women with symptomatic early pregnancy.

EDP: An Efficient Decomposition and Pruning Scheme for Convolutional Neural Network Compression.

Model compression methods have become popular in recent years, which aim to alleviate the heavy load of deep neural networks (DNNs) in real-world applications. However, most of the existing compression methods have two limitations: 1) they usually adopt a cumbersome process, including pretraining, training with a sparsity constraint, pruning/decomposition, and fine-tuning. Moreover, the last three stages are usually iterated multiple times. 2) The models are pretrained under explicit sparsity or low-rank assumptions, which are difficult to guarantee wide appropriateness. In this article, we propose an efficient decomposition and pruning (EDP) scheme via constructing a compressed-aware block that can automatically minimize the rank of the weight matrix and identify the redundant channels. Specifically, we embed the compressed-aware block by decomposing one network layer into two layers: a new weight matrix layer and a coefficient matrix layer. By imposing regularizers on the coefficient matrix, the new weight matrix learns to become a low-rank basis weight, and its corresponding channels become sparse. In this way, the proposed compressed-aware block simultaneously achieves low-rank decomposition and channel pruning by only one single data-driven training stage. Moreover, the network of architecture is further compressed and optimized by a novel Pruning & Merging (PM) module which prunes redundant channels and merges redundant decomposed layers. Experimental results (17 competitors) on different data sets and networks demonstrate that the proposed EDP achieves a high compression ratio with acceptable accuracy degradation and outperforms state-of-the-arts on compression rate, accuracy, inference time, and run-time memory.

Exosomal MicroRNAs in Serum as Potential Biomarkers for Ectopic Pregnancy.

DESIGN: From July 2016 to June 2018, 36 women with symptomatic early pregnancy around 4-8 weeks of gestation were recruited into the study. Among them, there were 16 women with viable intrauterine pregnancy (VIP), 9 women with spontaneous abortion (SA), and 11 women of EP. Serum exosomal miRNAs were extracted and measured at the first prenatal visit. Statistical analysis was performed to determine the clinical utility of these biomarkers as single markers and as multimarker panels for EP. RESULTS: Concentrations of miR-378d in serum exosomes were significantly higher in EP than in VIP and also SA group. As a single marker, miR-378d had the highest specificity of 64% at the sensitivity of 89.1%. Comparatively, both combined panels of hCG, progesterone, miR-100-5p and hCG, progesterone, and miR-215-5P yielded the specificity of 96%. Panels for all markers achieved the highest specificity of 80% at the sensitivity of 91%. CONCLUSIONS: Although further validation in large-scale prospective studies is necessary, our results suggest that serum exosomal miR-378d, miR-100-5p, and miR-215-5P are promising biomarkers for early EP.

Mechanism of Dayuanyin in the treatment of coronavirus disease 2019 based on network pharmacology and molecular docking.

BACKGROUND: At present, coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2, is spreading all over the world, with disastrous consequences for people of all countries. The traditional Chinese medicine prescription Dayuanyin (DYY), a classic prescription for the treatment of plague, has shown significant effects in the treatment of COVID-19. However, its specific mechanism of action has not yet been clarified. This study aims to explore the mechanism of action of DYY in the treatment of COVID-19 with the hope of providing a theoretical basis for its clinical application. METHODS: First, the TCMSP database was searched to screen the active ingredients and corresponding target genes of the DYY prescription and to further identify the core compounds in the active ingredient. Simultaneously, the Genecards database was searched to identify targets related to COVID-19. Then, the STRING database was applied to analyse protein-protein interaction, and Cytoscape software was used to draw a network diagram. The R language and DAVID database were used to analyse GO biological processes and KEGG pathway enrichment. Second, AutoDock Vina and other software were used for molecular docking of core targets and core compounds. Finally, before and after application of DYY, the core target gene IL6 of COVID-19 patients was detected by ELISA to validate the clinical effects. RESULTS: First, 174 compounds, 7053 target genes of DYY and 251 genes related to COVID-19 were selected, among which there were 45 target genes of DYY associated with treatment of COVID-19. This study demonstrated that the use of DYY in the treatment of COVID-19 involved a variety of biological processes, and DYY acted on key targets such as IL6, ILIB, and CCL2 through signaling pathways such as the IL-17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and cytokine-cytokine receptor interaction. DYY might play a vital role in treating COVID-19 by suppressing the inflammatory storm and regulating immune function. Second, the molecular docking results showed that there was a certain affinity between the core compounds (kaempferol, quercetin, 7-Methoxy-2-methyl isoflavone, naringenin, formononetin) and core target genes (IL6, IL1B, CCL2). Finally, clinical studies showed that the level of IL6 was elevated in COVID-19 patients, and DYY can reduce its levels. CONCLUSIONS: DYY may treat COVID-19 through multiple targets, multiple channels, and multiple pathways and is worthy of clinical application and promotion.

A Chinese Herbal Formula Suppresses Colorectal Cancer Migration and Vasculogenic Mimicry Through ROS/HIF-1α/MMP2 Pathway in Hypoxic Microenvironment.

Various malignant tumors, including colorectal cancer, have the ability to form functional blood vessels for tumor growth and metastasis. Vasculogenic mimicry (VM) refers to the ability of highly invasive tumor cells to link each other to form vessels, which is associated with poor cancer prognosis. However, the antitumor VM agents are still lacking in the clinic. Astragalus Atractylodes mixture (AAM), a traditional Chinese medicine, has shown to inhibit VM formation; however the exact mechanism is not completely clarified. In this study, we found that HCT-116 and LoVo could form a VM network. Additionally, hypoxia increases the intracellular reactive oxygen species (ROS) level and accelerates migration, VM formation in colorectal cancer cells, while N-Acetylcysteine (NAC) could reverse these phenomena. Notably, further mechanical exploration confirmed that the matrix metalloprotease 2 (MMP2) induction is ROS dependent under hypoxic condition. On the basis, we found that AAM could effectively inhibit hypoxia-induced ROS generation, migration, VM formation as well as HIF-1α and MMP2 expression. In vivo, AAM significantly inhibits metastasis of colorectal cancer in murine lung-metastasis model. Taken together, these results verified that AAM effectively inhibits migration and VM formation by suppressing ROS/HIF-1α/MMP2 pathway in colorectal cancer under hypoxic condition, suggesting AAM could serve as a therapeutic agent to inhibit VM formation in human colorectal cancer.

Genistein inhibits migration and invasion of cervical cancer HeLa cells by regulating FAK-paxillin and MAPK signaling pathways.

OBJECTIVE: Genistein obviously inhibits the migration and invasion of various tumor cells. However, its effects on cervical cancer cells have seldom been referred. We aimed to evaluate the effects of genistein on the proliferation, migration and invasion of cervical cancer HeLa cells, the expressions and phosphorylations of proteins related with FAK-paxillin and MAPKs signaling pathways, as well as the expressions of related key genes. MATERIALS AND METHODS: HeLa cells were stimulated with genistein for 24 h and 48 h respectively. After adherence for 2 h, 0 µM, 12.5 µM, 25 µM, 50 µM and 100 µM genistein solutions were added in DMEM. Cell proliferation was tested by the CCK-8 assay. After treatment with 100 µM genistein, the migration ability was detected by the scratch assay. Transwell assay was used to detect cell migration and invasion abilities. Western blot and qRT-PCR were used to detect the expressions of proteins and mRNAs related with FAK-paxillin and MAPKs signaling pathways respectively. RESULTS: The effect of genistein on the proliferation of HeLa cells was proportional to treatment time and drug dose, and the proliferation was inhibited after 24 h and 48 h at 100 µM. After treatment with 100 µM genistein, the scratch migration rate was significantly lower than that of the control group at 24 h and 48 h (P < 0.05). Genistein also inhibited the invasion of tumor cells through the upper chamber and Matrigel. The number of invasive cells was significantly lower than that of the control group (P < 0.05). Genistein significantly inhibited the phosphorylations of FAK, paxillin, p38 and p42/44. Compared to the control group, 100 µM genistein significantly suppressed the mRNA expressions of FAK, paxillin, Snail and twist. CONCLUSION: Genistein inhibited the migration and invasion of cervical cancer HeLa cells by regulating FAK-paxillin and MAPK signaling pathways in dose-dependent manners.

DkWRKY interacts with pyruvate kinase gene DkPK1 and promotes natural deastringency in C-PCNA persimmon.

PAs, also known as condensed tannins, cause the astringency sensation in the persimmon fruit. The astringency of Chinese pollination-constant non-astringent (C-PCNA) persimmon (Diospyros kaki Thunb.) can be naturally removed on the tree, but the regulatory mechanisms of deastringency remain to be elucidated. In our previous research, DkPK1 was shown to be involved in the natural loss of astringency of C-PCNA persimmon fruit. In the present study, yeast one-hybrid (Y1H) library screening using the DkPK1 promoter as baits identified two DkWRKY transcription factor genes (DkWRKY3 and -15). The transcript levels of both DkWRKY3 and -15 exhibited a positive correlation with the decrease in soluble proanthocyanidin (PA) content during the last developmental stage in C-PCNA persimmon. Multiple sequence analysis and subcellular localization confirmed that DkWRKY3 and -15 belonging to the group II and I families, respectively, were both located in the nucleus. Dual-luciferase and Y1H assays demonstrated that DkWRKY3 and -15 can transactivate the DkPK1 promoters. The combination of DkWRKY3 and -15 most likely produced an additive activation effect compared to a single activator on DkPK1, although the two transcriptional activators were not capable of interacting. Notably, DkWRKY3 and -15 showed ubiquitous expression in various organs and abundant upregulation in seeds. Furthermore, transient overexpression of both DkWRKY3 and -15 in persimmon leaves led to a significant decrease in the content of soluble PAs but a significant increase in the expression levels of the acetaldehyde metabolism-related DkPK, DkPDC and DkADH genes. Thus, we suggest that DkWRKY3 and -15 are the upstream regulators of DkPK1 and positively regulate the natural deastringency in C-PCNA persimmon.

Comparative transcriptomic analysis reveals genetic divergence and domestication genes in Diospyros.

BACKGROUND: Persimmon (Diospyros kaki) is the most economically cultivated species belonging to the genus Diospyros. However, little is known about the interspecific diversity and mechanism of domestication, partly due to the lack of genomic information that is available for closely related species of D. kaki (DK). Here, we performed transcriptome sequencing on nine samples, including DK, a variety of DK and seven closely related species, to evaluate the interspecific genetic divergence and to identify candidate genes involved in persimmon domestication. RESULTS: We obtained a total of 483,421 unigenes with N50 at 1490 bp in the nine Diospyros samples and identified 2603 orthogroups that were shared among all the samples using OrthoMCL analysis. A phylogenetic tree was established based on the tandem 2603 one-to-one single copy gene alignments, showing that DK was closely related to D. kaki var. silvestris (DKV) and that it clustered with the clade of D. deyangnsis (DD) and was farthest from the D. cathayensis (DC) species. The nonsynonymous substitutions (Ka), via synonymous substitution (Ks) ratios, was directly proportional to the genetic relationship of the different species. The higher the Ka/Ks ratios, the longer the distance was. Moreover, 31 positively selected genes (PSGs) involved in carbohydrate metabolism and phenolic metabolism were identified and isolated, and nearly all PSGs except the MATE gene had a high expression in the DK or DKV species. It was hypothesized that these genes might contribute to the domestication of the DK species. Finally, we developed the expressed sequence tag-simple sequence repeat (EST-SSR) and identified 2 unique amplicons DKSSR10 and DKSSR39: the former was absent in the DC species but was present in the other species, the latter had a long amplification product in the DJ species. CONCLUSION: This study presents the first transcriptome resources for the closely related species of persimmon and reveals interspecific genetic divergence. It is speculated that DK is derived from the hybridization of DD and DO species. Furthermore, our analysis suggests candidate PSGs that may be crucial for the adaptation, domestication, and speciation of persimmon relatives and suggests that DKSSR10 and DKSSSR39 could potentially serve as species-specific molecular markers.

The effects of environmental and socioeconomic factors on land-use changes: a study of Alberta, Canada.

Various environmental and socioeconomic issues have been attributed to land-use changes, and therefore, the underlying mechanisms merit investigation and quantification. This study assesses a comprehensive series of land-use conversions that were implemented over a recent 12-year period in the province of Alberta, Canada, where rapid economic and population growth has occurred. Spatial autocorrelation models are applied to identify the comprehensive effects of environmental and socioeconomic factors in each conversion case. The empirical results show that the impacts of key environmental and socioeconomic factors varied in intensity depending on the type of land-use conversion involved. Overall, land suitability for agricultural uses, road density, elevation, and population growth were found to be significant predictors of land-use changes. High land suitability, low elevation, and moderate road density were associated with land conversion for agricultural purposes.

[Inhibitory effect of telomerase inhibitors combined with X-irradiation on bone marrow hematopoiesis in mice].

The purpose of this study was to evaluate the effect of telomerase inhibitors combined with X-irradiation on bone marrow hematopoiesis in tumor-carrying mice. With an orthogonal experiment design, the telomerase inhibitors [azidothymidine, AZT 300 mg/(kg.day) and lamivudine 150 mg/(kg x day), per os, bid, x 2 weeks] and X-irradiation [total dose 10 Gy (2 Gy x 5) in 1 week] were used to treat BALB/c mice carrying breast cancer MA(782) for evaluating the influence on peripheral blood cells, bone marrow nucleated cells and telomerase activity. Telomerase activity was detected by a PCR-based telomeric repeat amplification protocol (TRAP) coupled with ELISA. The results showed that the number of marrow nucleated cells (x 10(7)/femur) was 2.1875 in untreated group, and 1.7375, 1.7500 and 1.3475 in irradiated, lamivudine and AZT groups, respectively, these suggested that AZT and irradiation could obviously decrease the number of marrow nucleated cells (P< 0.01 or P < 0.05). The peripheral WBC increased 3.7% in untreated mice, and irradiation, lamivudine and AZT reduced 18.09%, 16.19% and 41.00% of WBC, respectively (P < 0.05). Irradiation, lamivudine and AZT showed no obvious effect on RBC and platelet counts (P > 0.05). The telomerase activity (A(450) nm) of marrow cells was 1.498, 1.483, 0.816 and 0.727 in untreated, irradiation, lamivudine and AZT groups, respectively. It is concluded that AZT and lamivudine combined with X-irradiation inhibit bone marrow nucleate cells and the peripheral WBC, manifest inhibitory effect on telomerase activity in murine bone marrow, but have no effect on the peripheral RBC and platelet.