Metabolomics study of the hepatoprotective effect of total flavonoids of Mallotus apelta leaf in carbon tetrachloride-induced liver fibrosis in rats.

Mallotus apelta leaf, recorded in the quality standard of Yao Medicinal Material in Guangxi Zhuang autonomous region, is commonly used in the treatment of liver diseases. Total flavonoids of M. apelta leaf (TFM) had good anti-fibrosis activity, but the anti-fibrosis mechanism of TFM is still unclear. Nuclear magnetic resonance technology was used to study the dynamic changes of urine metabolites in CCl4 -induced liver fibrosis before and after TFM treatment. Ingenuity Path Analysis (IPA) was used to find potential target genes for TFM to improve liver fibrosis and verify the expression of target genes by real-time fluorescent quantitative PCR and Western blotting. TFM can significantly reduce serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) levels, improve liver steatosis and reduce inflammation; in urine metabolomics, a total of seven potential biomarkers were found, mainly involving two metabolic pathways; IPA analysis showed that TNF may be a potential target for TFM to improve liver fibrosis induced by CCl4 in rats. This study found that TNF may be a potential target gene for TFM treatment of liver fibrosis, and shows that the anti-fibrosis mechanism of TFM could improve liver fibrosis by regulating the tricarboxylic acid cycle and subtaurine metabolism.

Toward Highly Selective Heteroatom Dopants in Hard Carbon with Superior Lithium Storage Performance.

Hard carbons (HCs) have gained much attention for next-generation high energy density lithium-ion battery (LIB) anode candidates. However, voltage hysteresis, low rate capability, and large initial irreversible capacity severely affect their booming application. Herein, a general strategy is reported to fabricate heterogeneous atom (N/S/P/Se)-doped HC anodes with superb rate capability and cyclic stability based on a three-dimensional (3D) framework and a hierarchical porous structure. The obtained N-doped hard carbon (NHC) exhibits an excellent rate capability of 315 mA h g-1 at 10.0 A g-1 and a long-term cyclic stability of 90.3% capacity retention after 1000 cycles at 3 A g-1. Moreover, the as-constructed pouch cell delivers a high energy density of 483.8 W h kg-1 and fast charging capability. The underlying mechanisms of lithium storage are illustrated by electrochemical kinetic analysis and theoretical calculations. It is demonstrated that heteroatom doping imposes significant effects on adsorption and diffusion for Li+. The versatile strategy in this work opens an avenue for rational design of advanced carbonaceous materials with high performance for LIB applications.

Zn2+-interference and H2S-mediated gas therapy based on ZnS-tannic acid nanoparticles synergistic enhancement of cell apoptosis for specific treatment of prostate cancer.

Zn2+ and H2S are essential to maintain normal prostate function, and sometimes can evolve into weapons to attack and destroy prostate cancer (PCa) cells. Nevertheless, how to achieve the targeted and effective release of Zn2+ and H2S, and reverse the concentration distribution within PCa tumor cells still highly challenging. Herein, combined with these pathological characteristics of prostate, we proposed a tumor microenvironment (TME) responsive Zn2+-interference and H2S-mediated gas synergistic therapy strategy based on a nanoplatform of tannic acid (TA) modified zinc sulfide nanoparticles (ZnS@TA) for the specific treatment of PCa. Once the constructed pH-responsive ZnS@TA internalized by cancer cells, it would instantaneously decomposed in acidic TME, and explosively release excess Zn2+ and H2S exceeding the cell self-regulation threshold. Meanwhile, the in situ produced Zn2+ and H2S synergistic enhancement of cell apoptosis, which is evidenced to increase levels of Bax and Bax/Bcl-2 ratio, release of Cytochrome c in cancer cells, contributing to inhibit the growth of tumor. Moreover, the TA in cooperation with Zn2+ specifically limits the migration and invasion of PCa cells. Both in vitro and in vivo results demonstrate that the Zn2+-interference in combination with H2S-mediated gas therapy achieves an excellent anti-tumor performance. Overall, this nanotheranostic synergistic therapy provides a promising direction for exploring new strategies for cancer treatment based on specific tumor pathological characteristics, and provides a new vision for promoting practical cancer therapy.

Injectable Immunotherapeutic Thermogel for Enhanced Immunotherapy Post Tumor Radiofrequency Ablation.

Tumor radiofrequency ablation (RFA) is a local and minimally invasive application using high temperature to induce coagulative necrosis of tumor, which has been commonly used in clinic. Although the tumor fragments generated by RFA can activate the host's immune system, it may be insufficient to inhibit cancer recurrence due to many factors such as the inefficient antigen presentation by dendritic cells (DCs). In this research, a convenient local administration strategy by blocking rho-associated kinases (ROCK) is applied to amplify the immune responses triggered by RFA via promoting the phagocytosis capacity of DCs. Briefly, ROCK inhibitor, Y27632, is successfully dispersed in the amphiphilic copolymer poly(D,L-lactide-co-glycolide)-b-poly(ethyleneglycol)-b-poly(D,L-lactideco-glycolide) (PLGA-PEG-PLGA) solution, which is sol at room temperature and forms hydrogel quickly at body temperature, obviously prolonging the retention of Y27632 after injection. Interestingly, in the melanoma tumor model, the generated tumor fragments after RFA treatment are swallowed by DCs and undergo reinforced antigen presentation process with the help of gradual released Y27632, further effectively activating T cell mediated anti-tumor immune responses and significantly improving the therapeutic efficiency of RFA. Overall, such strategy remarkably prolongs the survival of mice after RFA treatment, showing great potential for clinical translation as an improvement strategy for RFA.

Deciphering the effects of PYCR1 on cell function and its associated mechanism in hepatocellular carcinoma.

Overexpression of pyrroline-5-carboxylate reductase 1 (PYCR1) has been associated with the development of certain cancers; however, no studies have specifically examined the role of PYCR1 in hepatocellular carcinoma (HCC). Based on The Cancer Genome Atlas expression array and meta-analysis conducted using the Gene Expression Omnibus database, we determined that PYCR1 was upregulated in HCC compared to adjacent nontumor tissues (P < 0.05). These data were verified using quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry analysis. Additionally, patients with low PYCR1 expression showed a higher overall survival rate than patients with high PYCR1 expression. Furthermore, PYCR1 overexpression was associated with the female sex, higher levels of alpha-fetoprotein, advanced clinical stages (III and IV), and a younger age (< 45 years old). Silencing of PYCR1 inhibited cell proliferation, invasive migration, epithelial-mesenchymal transition, and metastatic properties in HCC in vitro and in vivo. Using RNA sequencing and bioinformatics tools for data-dependent network analysis, we found binary relationships among PYCR1 and its interacting proteins in defined pathway modules. These findings indicated that PYCR1 played a multifunctional role in coordinating a variety of biological pathways involved in cell communication, cell proliferation and growth, cell migration, a mitogen-activated protein kinase cascade, ion binding, etc. The structural characteristics of key pathway components and PYCR1-interacting proteins were evaluated by molecular docking, and hotspot analysis showed that better affinities between PYCR1 and its interacting molecules were associated with the presence of arginine in the binding site. Finally, a candidate regulatory microRNA, miR-2355-5p, for PYCR1 mRNA was discovered in HCC. Overall, our study suggests that PYCR1 plays a vital role in HCC pathogenesis and may potentially serve as a molecular target for HCC treatment.

Diagnostic potential of trace metals concentration in expressed prostatic secretion and serum of patients with category IV prostatitis.

BACKGROUND: The National Institutes of Health (NIH) category IV prostatitis is a painless prostate gland inflammation, just as its name implies, this type of prostatitis is related with inflammation of the prostate, but most men are not conscious of it. However, category IV prostatitis is fairly common in general populations and reported having indirect relationships with prostate cancer. METHOD: We analyzed the concentration of zinc (Zn), copper (Cu), calcium (Ca) and magnesium (Mg) in expressed prostatic secretion (EPS) and serum of patients with category IV prostatitis and healthy controls, investigating the diagnostic potential of different metals in category IV prostatitis using a flame atomic absorption spectrometer (FAAS). RESULTS: Metal concentration combined clinical characteristics analysis suggested that average level of Zn, Ca, Mg were significantly lower in the EPS of patients with category IV prostatitis (P-value< 0.000), while Cu level raised obviously (P-value< 0.000). And in the serum, mean concentrations of Ca was also found to increase significantly in the patients with category IV prostatitis compared to healthy controls. Moreover, the correlation analysis indicated that age showed a positive correlation with EPS Zn, Ca, Mg concentration (P-value< 0.05), while albumin correlates with EPS Zn, Ca, Mg concentration reversely (P-value< 0.05) in patients with category IV prostatitis. CONCLUSION: Our report revealed that determination of the metal elements zinc, copper, calcium and magnesium in the serum and EPS could be a new and promising strategy for the rapid diagnosis of category IV prostatitis.

Increased SPC24 in prostatic diseases and diagnostic value of SPC24 and its interacting partners in prostate cancer.

SPC24 is a crucial component of the mitotic checkpoint machinery in tumorigenesis. High levels of SPC24 have been found in various cancers, including breast cancer, lung cancer, liver cancer, osteosarcoma and thyroid cancer. However, to the best of our knowledge, the impact of SPC24 on prostate cancer (PCa) and other prostate diseases remains unclear. In the present study expression of global SPC24 messenger RNA (mRNA) was assessed in a subset of patients with PCa included in The Cancer Genome Atlas (TCGA) database. Increased levels of SPC24 expression were found in PCa patients >60 years old compared to patients <60 and increased SPC24 expression was also associated with higher levels of prostate specific antigen (P<0.05) and lymph node metastasis (P<0.05). Higher levels of SPC24 expression were associated with negative outcomes in PCa patients (P<0.05). Furthermore, in Chinese patients with prostatitis, benign prostatic hypertrophy (BPH) and PCa, SPC24 was expressed at significantly higher levels than that in adjacent/normal tissues, as assessed by reverse transcription-quantitative polymerase chain reaction, immunohistochemistry and western blotting. High expression of SPC24 was associated with high Gleason stages (IV and V; P<0.05). Further analysis, based on Gene Ontology and pathway functional enrichment analysis, suggested that nuclear division cycle 80 (NDC80), an SPC24 protein interaction partner, and mitotic spindle checkpoint serine/threonine-protein kinase BUB1 (BUB1), a core subunit of the spindle assembly checkpoint, may be associated with SPC24 in PCa development. Finally, using binary logistic regression, algorithms combining the receiver operating characteristic between SPC24 and BUB1 or NDC80 indicated that a combination of these markers may provide better PCa diagnosis ability than other PCa diagnosis markers. Taken together, these findings suggest that SPC24 may be a promising prostate disease biomarker.

Injectable Reactive Oxygen Species-Responsive SN38 Prodrug Scaffold with Checkpoint Inhibitors for Combined Chemoimmunotherapy.

Chemotherapeutic agents have been widely used for cancer treatment in clinics. Aside from their direct cytotoxicity to cancer cells, some of them could activate the immune system of the host, contributing to the enhanced antitumor activity. Here, the reactive oxygen species (ROS)-responsive hydrogel, covalently cross-linked by phenylboronic acid-modified 7-ethyl-10-hydroxycamptothecin (SN38-SA-BA) with poly(vinyl alcohol) (PVA), is fabricated for topical delivery of anti-programmed cell death protein ligand 1 antibodies (aPDL1). In the presence of endogenous ROS, SN38-SA-BA will be oxidized and hydrolyzed, leading to the degradation of hydrogel and the release of initial free SN38 and encapsulated aPDL1. It is demonstrated that SN38 could elicit specific immune responses by triggering immunogenic cell death (ICD) of cancer cells, a distinct cell death pathway featured with the release of immunostimulatory damage-associated molecular patterns (DAMPs). Meanwhile, the released aPDL1 could bind to programmed cell death protein ligand 1 (PDL1) expressed on cancer cells to augment antitumor T cell responses. Thus, the ROS-responsive prodrug hydrogel loaded with aPDL1 could induce effective innate and adaptive antitumor immune responses after local injection, significantly inhibiting or even eliminating those tumors.

Nervilifordin F alleviates intestinal ischemia/reperfusion-induced acute lung injury via inhibiting inflammasome and mTOR pathway.

Acute lung injury (ALI) is a life-threatening disorder with high rates of morbidity and mortality. Up to now, there are still no effective drugs for its therapies due to the complexity of its etiology and pathogenesis. In this present study, we investigated the protective effect of Nervilifordin F (NF) on ALI induced by intestinal ischemia/reperfusion (II/R) and its related mechanism. Firstly, the ALI model rats were induced through II/R, and treated with NF. Then, the pathological and cytokine level changes in the lung tissue of ALI rats were evaluated by hematoxylin and eosin and enzyme-linked immunosorbent assay (ELISA). The related genes expression level of mammalian target of rapamycin (mTOR) pathway and inflammasome were measured by real-time quantitative polymerase chain reaction (RT-qPCR), western blot and immunohistochemistry. Finally, the NF-protein complexes were predicted by SYBYL-X 2.0. The results indicated that NF can significant reduces the levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 and IL-1ß, and inhibits the expression of inflammasome related genes (such as toll-like receptor 4 (TLR4), p65, NOD-like receptor protein 3 (NLRP3) and Caspase 1), thereby reduce inflammation in II/R-induced ALI rats. Moreover, NF can activate the expression of FK506 binding protein 25 (FKBP25) and down-regulate the expression of mTOR and p70 ribosomal protein S6 kinase 1 (p70S6K). In addition, molecular docking results showed that NF can be combined well with p70S6K, TLR4, mTOR and NLRP3, which further verified the inhibitory effect of NF on ALI inflammation. Therefore, the findings indicate that NF can alleviates II/R-induced inflammation of ALI rats by inhibiting inflammasome related genes and mTOR pathway, which expected to use as a potential drug for the treatment of ALI.

Injectable Anti-inflammatory Nanofiber Hydrogel to Achieve Systemic Immunotherapy Post Local Administration.

Despite the great promise achieved by immune checkpoint blockade (ICB) therapy in harnessing the immune system to combat different tumors, limitations such as low objective response rates and adverse effects remain to be resolved. Here, an anti-inflammatory nanofiber hydrogel self-assembled by steroid drugs is developed for local delivery of antiprogrammed cell death protein ligand 1 (αPDL1). Interestingly, on the one hand this carrier-free system based on steroid drugs can reprogram the pro-tumoral immunosuppressive tumor microenvironment (TME) to antitumoral TME; on the other hand, it would serve as a reservoir for sustained release of αPDL1 so as to synergistically boost the immune system. By local injection of such αPDL1-loaded hydrogel, effective therapeutic effects were observed in inhibiting both local tumors and abscopal tumors without any treatment. This work presents a unique hydrogel-based delivery system using clinically approved drugs, showing promise in improving the objective response rate of ICB therapy and minimizing its systemic toxicity.

The impact of MCM6 on hepatocellular carcinoma in a Southern Chinese Zhuang population.

Minichromosome maintenance complex component 6 (MCM6) is involved in tumorigenesis of hepatocellular carcinoma (HCC). Because its effect on different populations remains unclear, this study investigated the impact of MCM6 on HCC in Southern Chinese Zhuang population. In addition to assessing the global mRNA levels of MCM6 based on The Cancer Genome Atlas database (TCGA) and The Gene Expression Omnibus database (GEO), associations between MCM6 mRNA levels and clinicopathological features were analyzed. High MCM6 levels were associated with high alpha-fetoprotein (AFP) (>20 ng/mL in serum) (P < 0.0001) and advanced clinical stage (III + IV) (P < 0.001). Higher MCM6 was associated with poorer outcomes (P < 0.01) in these databases. Furthermore, the mRNA and protein expression of MCM6 in the Guangxi Zhuang population was detected by quantitative polymerase chain reaction (qPCR), western blot, and immunohistochemistry (IHC). The results showed that MCM6 levels were up-regulated in the Zhuang population with HCC. Higher MCM6 protein levels were correlated with larger tumor size (>5 cm) (P = 0.038) and advanced clinical stage (III + IV) (p = 0.023). Bioinformatic enrichment analysis of MCM6 and its interacting proteins (CDT1,WEE1,TRIM28 and MKI67) suggested that in addition to being involved in the cell cycle process, these complexes could also be involved in protein binding, pre-replication complex assemble, and nucleus metabolism. Based on the protein-protein interaction (PPI) network with module screen, the interactions between MCM6 and its potential interacting proteins were further studied through protein docking with hot spot analysis. Additionally, the results of the algorithms combining the ROC of MCM6 and its interacting proteins showed that combination biomarker analysis has better HCC diagnosis ability than the single MCM6 test. The combination of MCM6 and TRIM28 was more suitable for the Guangxi Zhuang population. Overall, our study suggests that MCM6 plays an important role in the growth of HCC. MCM6 could be an optimal biomarker for diagnosing HCC and a potential molecular target for HCC therapy in the Zhuang population.

IVS8-5T Allele of CFTR is the Risk Factor in Chronic Pancreatitis, Especially in Idiopathic Chronic Pancreatitis.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator IVS8-5T gene variation appears to be associated with a higher risk of chronic pancreatitis (CP); however, there is inconsistency between previous reported studies. Here, we performed a meta-analysis to investigate this relationship. MATERIALS AND METHODS: PubMed and WANFANG databases were searched for the case-control studies that contained Patients with CP with IVS8-5T variation. Odd ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the relevance of IVS8-5T gene variation and CP. RESULTS: Analysis showed that the frequency of the 5T allele was significantly higher in CP subjects than that in control subjects (OR = 1.43, 95% CI: 1.13-1.81, I2 = 1.2%). Based on the subgroup analysis stratified by etiology, the 5T allele was associated with a higher risk of idiopathic chronic pancreatitis (ICP) (OR = 1.80, 95% CI: 1.18-2.76, I2 = 0.0%) and not alcoholic CP (OR = 2.14, 95% CI: 0.98-4.66, I2 = 0.0%). Further study indicated that the 5T allele was related to higher ICP prevalence in the European population (OR = 1.79, 95% CI: 1.06-3.03, I2 = 0.0%). In contrast, there was no significant difference between ICP subjects and healthy controls within the Asian population (OR = 1.84, 95% CI: 0.91-3.72, I2 = 38.0%). CONCLUSIONS: Cystic fibrosis transmembrane conductance regulator IVS8-5T is a risk factor in patients with CP. IVS8-5T variation may play a significant role in the occurrence of ICP, especially in the European population.

Hepatoprotective effect of total flavonoids of Mallotus apelta (Lour.) Muell.Arg. leaf against carbon tetrachloride-induced liver fibrosis in rats via modulation of TGF-ß1/Smad and NF-κB signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: The Mallotus apelta (Lour.) Muell.Arg. is a well-known traditional Chinese medicine (TCM) used for anti-inflammatory, hemostasis and chronic hepatitis. AIM: The purpose of this study was to explore the antifibrotic effect of total flavonoids of Mallotus apelta leaf (TFM) and its potential mechanism. METHODS: Hepatic fibrosis was induced by carbon tetrachloride (CCl4) in rats. The CCl4-induced rats received intragastric administration of colchicine (0.2 mg/kg per day), TFM (25, 50, 100 mg/kg per day) and the equal vehicle was given to normal rats. Pathological evaluation in hepatic tissue were examined by hematoxylin and eosin (HE) staining. And the levels of serum biochemical parameters were detected by automatic biochemical analysis. Meanwhile, the collagen deposition in liver was observed by staining with Masson's trichrome. Collagenic parameters and inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA) kits. Additionally, corresponding assay kit was used to estimate the antioxidant enzyme and lipid peroxidation. In order to explore the potential mechanism of anti-fibrotic effects in TFM, the expressions of liver fibrosis related gene and protein were analyzed by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot. RESULTS: The CCl4-induced hepatic fibrosis were inhibited dose-dependently in rats by TFM. The results showed that the key hallmarks of liver injury including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), albumin (ALB) and total protein (TP) in the serum were reversed in CCl4-induced hepatic fibrosis rats which were treated by TFM. Furthermore, TFM significantly alleviates collagen accumulation and reduces the contents of hydroxyproline (Hyp), Type III precollagen (PC-III), collagen I (Col I), hyaluronic acid (HA) and laminin (LN). RT-PCR and Western blot results showed that TFM markedly inhibits liver fibrosis hallmark factor α-smooth muscle actin (α-SMA) expressions in CCl4-induced hepatic fibrosis rats. Moreover, TFM alleviated the oxidative stress and lipid peroxidation in rats induced by CCl4. TFM also attenuated the pro-inflammatory cytokines including interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) via inhibiting nuclear factor-κB (NF-κB) activation. Meanwhile, transforming growth factor-ß1 (TGF-ß1)/Smad signaling pathway was inhibited by TFM treatment. CONCLUSIONS: TFM can alleviate CCl4-induced hepatic fibrosis in rats, which potential mechanism may be due to its ability of reducing ECM accumulation, improving antioxidant and regulating TGF-ß1/Smad signaling pathways and NF-κB-dependent inflammatory response.

Enhanced electrical conductivity and piezoresistive sensing in multi-wall carbon nanotubes/polydimethylsiloxane nanocomposites via the construction of a self-segregated structure.

Formation of highly conductive networks is essential for achieving flexible conductive polymer composites (CPCs) with high force sensitivity and high electrical conductivity. In this study, self-segregated structures were constructed in polydimethylsiloxane/multi-wall carbon nanotube (PDMS/MWCNT) nanocomposites, which then exhibited high piezoresistive sensitivity and low percolation threshold without sacrificing their mechanical properties. First, PDMS was cured and pulverized into 40-60 mesh-sized particles (with the size range of 250-425 µm) as an optimum self-segregated phase to improve the subsequent electrical conductivity. Then, the uncured PDMS/MWCNT base together with the curing agent was mixed with the abovementioned PDMS particles, serving as the segregated phase. Finally, the mixture was cured again to form the PDMS/MWCNT nanocomposites with self-segregated structures. The morphological evaluation indicated that MWCNTs were located in the second cured three-dimensional (3D) continuous PDMS phase, resulting in an ultralow percolation threshold of 0.003 vol% MWCNTs. The nanocomposites with self-segregated structures with 0.2 vol% MWCNTs achieved a high electrical conductivity of 0.003 S m-1, whereas only 4.87 × 10-10 S m-1 was achieved for the conventional samples with 0.2 vol% MWCNTs. The gauge factor GF of the self-segregated samples was 7.4-fold that of the conventional samples at 30% compression strain. Furthermore, the self-segregated samples also showed higher compression modulus and strength as compared to the conventional samples. These enhanced properties were attributed to the construction of 3D self-segregated structures, concentrated distribution of MWCNTs, and strong interfacial interaction between the segregated phase and the continuous phase with chemical bonds formed during the second curing process. These self-segregated structures provide a new insight into the fabrication of elastomers with high electrical conductivity and piezoresistive sensitivity for flexible force-sensitive materials.

[Potential endocrine disrupting effects of bifenthrin in rats].

OBJECTIVE: To study the potential endocrine disrupting effects of bifenthrin (BIF) by using uterotrophic assay and Hershberger assay. METHODS: In uterotrophic assay, 60 female SD rats were randomly divided into 6 groups, 10 rats per group. Rats in bifenthrin-treated groups were given different doses of bifenthrin (1.47, 4.41 and 13.23 mg/kg BW by gavage for 3 consecutive days). Rats in negative control groups were given corn oil by gavage. Rats in ethinyl estradiol (EE) oral positive control groups were given EE 1.0 microg/kg BW by gavage. Rats in EE injected positive groups were given 0.6 microg/kg BW EE by subcutaneously injection while given corn oil by gavage. At necropsy, the wet and blotted uteri were weighed. The relative uteri weights were calculated, and the histology of uteri was observed. In Hershberger assay, 60 castrated male SD rats were randomly divided into 6 groups, with 10 rats in each group. Rats in BIF-treated groups were given different doses of BIF (1.4, 4.2 and 12.6 mg/kg BW) by gavage. Flutamide (3.0 mg/kg BW) were given to animals in the positive control group by gavage. Rats in the negative control group and testosterone propionate group were given corn oil by gavage for 10 consecutive days. Rats in all groups except the negative control group were also treated with testosterone propionate (TP, 0.2 mg/kg BW) by subcutaneous injection. At necropsy, ventral prostate (VP), seminal vesicle plus fluids and coagulating glands (SVCG), levator ani-bulbocavernosus muscle (LABC), paired Cowper's glands (COW) and the glands penis (GP), liver, kidneys, adrenals were weighed. Serum triiodothyronine (T3) and thyroxine (T4) were determined. RESULTS: In uterotrophic assay, compared with the negative control group, the mean relative wet weight and relative blotted weight of uterine were increased significantly in the female rats given by BIF at 13.23 mg/kg BW for 3 days (P < 0.05). BIF resulted in a significant increase of epithelial cell heights of uteri at 4.41 and 13.23 mg/kg BW, as compared with control group. In Hershberger assay, compared with the TP group, mean absolute weight and relative weight of VP and LABC in BIF high dose group were significant decreased. Moreover, total T3 and T4 level were decreased also (P < 0.05). CONCLUSION: Uterotrophic assay and Hershberger assay used in this study showed that BIF may have endocrine disrupting properties.