Identification of the human Cytochrome P450 enzymes (P450s) responsible for metabolizing infigratinib to its pharmacologically active Metabolites, BHS697, and CQM157, and assessment of their in vitro inhibition of P450s and UDP-glucuronosyltransferases (UGTs).

Infigratinib, an oral FGFR inhibitor for advanced cholangiocarcinoma, yielded two active metabolites, BHS697 and CQM157, with similar receptor affinity. Our study characterized P450s that are responsible for the metabolism of infigratinib to its two major active metabolites, BHS697 and CQM157. In vitro inhibition of P450s and UGTs by infigratinib, BHS697 or CQM157 was further investigated. The unbound apparent Km values for metabolism of infigratinib to BHS697 by HLM, human recombinant CYP2C8, CYP2C19, CYP2D6 and CYP3A4 enzymes are 4.47, 0.65, 2.50, 30.6 and 2.08 µM, while Vmax values are 90.0 pmol/min/mg protein, 0.13, 0.027, 0.81, and 0.56 pmol/min/pmol protein, respectively. The unbound apparent Km value for metabolism of infigratinib to CQM157 by HLM is 0.049 µM, while the Vmax value is 0.32 pmol/min/mg protein respectively. In HLM, infigratinib displayed moderate inhibition of CYP3A4 and CYP2C19 and weak or negligible inhibition of other P450 isoforms. BHS697 exhibited weak inhibition of CYP2B6, CYP2C9, CYP2C19 and CYP3A4, and no inhibition of CYP2C8 and CYP2D6. CQM157 moderately inhibited CYP2C9 and CYP3A4, and weakly or negligibly inhibited other P450 isoforms. Regarding UGTs, infigratinib moderately inhibited UGT1A4 and weakly inhibited UGT1A1, respectively. BHS697 weakly inhibited UGT1A1. In contrast, CQM157 moderately inhibited both UGT1A1 and UGT1A4. Our findings provide novel insights into the metabolism of and potential DDIs implicating infigratinib.

Pathogenic fungi synergistically cooperate with Serratia marcescens to increase cockroach mortality.

The abuse of chemical insecticides has led to strong resistance in cockroaches, and biopesticides with active ingredients based on insect pathogens have good development prospects; however, their slow effect has limited their practical application, and improving their effectiveness has become an urgent problem. In this study, the interaction between Serratia marcescens and Metarhizium anisopliae enhanced their virulence against Blattella germanica and exhibited a synergistic effect. The combination of S. marcescens and M. anisopliae caused more severe tissue damage and accelerated the proliferation of the insect pathogen. The results of high-throughput sequencing demonstrated that the gut microbiota was dysbiotic, the abundance of the opportunistic pathogen Weissella cibaria increased, and entry into the hemocoel accelerated the death of the German cockroaches. In addition, the combination of these two agents strongly downregulated the expression of Imd and Akirin in the IMD pathway and ultimately inhibited the expression of antimicrobial peptides (AMPs). S. marcescens released prodigiosin to disrupted the gut homeostasis and structure, M. anisopliae released destruxin to damaged crucial organs, opportunistic pathogen Weissella cibaria overproliferated, broke the gut epithelium and entered the hemocoel, leading to the death of pests. These findings will allow us to optimize the use of insect pathogens for the management of pests and produce more effective biopesticides.

Prenylated indole diketopiperazine alkaloids as phosphatase inhibitors from the marine-derived fungus Talaromyces purpureogenus.

Six previously undescribed prenylated indole diketopiperazine alkaloids, talaromyines A-F (1-6), were isolated from the marine-derived fungus Talaromyces purpureogenus SCSIO 41517. Their structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic data including NMR, HR-ESI-MS, and electronic circular dichroism calculations, together with chemical analysis of hydrolysates. Compounds 1-5 represent the first example of spirocyclic indole diketopiperazines biosynthesized from the condensation of L-tryptophan and L-alanine. Compounds 2 and 4-5 showed selective inhibitory activities against phosphatases TCPTP and MEG2 with IC50 value of 17.9-29.7 µM, respectively. Compounds 4-5 exhibited mild cytotoxic activities against two human cancer cell lines H1975 and HepG-2.

Carotane sesquiterpenoids A-G from the desert endophytic fungus Fusarium sp. HM 166.

Seven undescribed carotane sesquiterpenoids named fusanoids A-G (1-7), along with one known analog (8) and two known sesterterpenes (9 and 10), were isolated from the fermentation broth of the desert endophytic fungi Fusarium sp. HM166. The structures of the compounds, including their absolute configurations, were determined by spectroscopic data, single-crystal X-ray diffraction analysis, and ECD calculations. Compound 10 showed cytotoxic activities against human hepatoma carcinoma cell line (Huh-7) and human breast cell lines (MCF-7 and MDA-MB-231), and compound 2 showed cytotoxic activity against MCF-7, while compounds 4-9 were inactive against all the tested cell lines. Compounds 4 and 10 showed potent inhibitory activities against the IDH1R132h mutant.

Lidocaine hampers colorectal cancer process via circITFG2/miR-1204/SOCS2 axis.

Colorectal cancer (CRC) is a deadly disease with a poor prognosis. Lidocaine is preferred by surgical procedures due to the excellent anesthesia. Circular RNA integrin alpha FG-GAP repeat containing 2 (circITFG2) has been recognized as a momentous participator in CRC progression. The specific role of circITFG2 was further studied in this research. Quantitative real-time PCR (qRT-PCR) was devoted to examining the expression of circITFG2, microRNA-1204 (miR-1204) and SOCS2 mRNA in CRC cells. Western blot was used to determine SOCS2 protein expression in CRC cells. Cell viability, colony formation and apoptosis were detected by cell counting kit-8 (CCK-8) assay, colony formation assay and flow cytometry assay respectively. Cell migration and invasion were tested by wound healing assay and transwell assay. Dual-luciferase reporter system, RNA pull down and RNA-binding protein immunoprecipitation (RIP) assays were applied to verify the combination between miR-1204 and circITFG2 or SOCS2. CircITFG2 was strikingly downregulated; however, lidocaine treatment induced a significant increase in the expression of circITFG2 and SOCS2 and a decrease in miR-1204 expression in CRC cells. Meanwhile, SOCS2 protein expression was upregulated by lidocaine treatment or miR-1204 silence in CRC cells and downregulated by circITFG2 knockdown or miR-1204 overexpression in lidocaine-treated CRC cells. CircITFG2 knockdown or miR-1204 overexpression abolished lidocaine-induced inhibition in proliferation, metastasis and promotion in apoptosis in CRC cells. CircITFG2 overexpression, SOCS3 overexpression or lidocaine treatment suppressed proliferation, metastasis and facilitated apoptosis in CRC cells. CircITFG2 sponged miR-1204 to regulate SOCS3 expression in lidocaine-treated CRC cells. Lidocaine hindered CRC progression by circITFG2/miR-1204/SOCS2 axis. This finding might beat a path in improving CRC therapy.

Isoquinoline Alkaloids as Protein Tyrosine Phosphatase Inhibitors from a Deep-Sea-Derived Fungus Aspergillus puniceus.

Puniceusines A-N (1-14), 14 new isoquinoline alkaloids, were isolated from the extracts of a deep-sea-derived fungus, Aspergillus puniceus SCSIO z021. Their structures were elucidated by spectroscopic analyses. The absolute configuration of 9 was determined by ECD calculations, and the structures of 6 and 12 were further confirmed by a single-crystal X-ray diffraction analysis. Compounds 3-5 and 8-13 unprecedentedly contained an isoquinolinyl, a polysubstituted benzyl or a pyronyl at position C-7 of isoquinoline nucleus. Compounds 3 and 4 showed selective inhibitory activity against protein tyrosine phosphatase CD45 with IC50 values of 8.4 and 5.6 µM, respectively, 4 also had a moderate cytotoxicity towards human lung adenocarcinoma cell line H1975 with an IC50 value of 11.0 µM, and 14, which contained an active center, -C=N+, exhibited antibacterial activity. An analysis of the relationship between the structures, enzyme inhibitory activity and cytotoxicity of 1-14 revealed that the substituents at C-7 of the isoquinoline nucleus could greatly affect their bioactivity.

Efficacy and safety of WBRT+EGFR-TKI versus WBRT only in the treatment of NSCLC patients with brain metastasis: An updated meta-analysis.

BACKGROUND: To investigate the efficacy and safety of whole brain radiotherapy (WBRT) combined with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) versus WBRT only in the treatment of brain metastasis in non-small cell lung cancer (NSCLC) patients by pooling open published data. METHODS: Prospective clinical studies relevant to WBRT+EGFR-TKI versus WBRT only in the treatment of NSCLC brain metastasis were electronically searched in the Pubmed, EMbase, Cochrane, Wangfang, CNKI and Google scholar databases. The treatment response, 1-year survival and treatment-associated toxicity were pooled and expressed by odds ratio (OR) under a fixed or random effect model. The publication bias was evaluated by Begg's funnel plot and Egger's line regression test. RESULTS: Eighteen prospective clinical studies were included in the study. The combined results indicated that the objective response rate (ORR) in the WBRT+TKI group was superior to WBRT only with a statistical difference (OR = 2.67, 95% CI: 2.10-3.38, p < 0.05) under a fixed effect model. Ten studies reported the 1-year survival rate between the WBRT+TKI and WBRT only groups. The combined results showed that 1-year survival rate in the WBRT+TKI group was higher than that of the WBRT only group with a statistical difference (OR = 2.70, 95% CI: 1.95-3.74, p < 0.05). For treatment-associated toxicity, the combined data indicated that the treatment-related rash in the WBRT+TKI group was significantly higher than that of the WBRT only group with a statistical difference (OR = 2.72, 95% CI: 1.53-4.84, p < 0.05). However, the incidence of nausea/vomiting (OR = 0.84, 95% CI: 0.60-1.17, p > 0.05), diarrhea (OR = 1.31, 95% CI: 0.83-2.07, p > 0.05), fatigue (OR = 1.40, 95% CI: 0.70-2.81, p > 0.05) and myelosuppression (OR = 0.86, 95% CI: 0.56-1.32, p > 0.05) were not statistically different between the two groups. CONCLUSIONS: Based on the current publications, WBRT+EGFR-TKI can improve the treatment response and 1-year survival rate but not increase the toxicity except for rash compared to WBRT alone in the treatment of brain metastasis in NSCLC patients.

[Effect of Nrf2/HO-1 signaling pathway in intestinal protection by Sishen Pills against ulcerative colitis in mice].

The present study aimed to explore the effect of nuclear factor erythroid 2 related factor 2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway in intestinal protection by Sishen Pills against ulcerative colitis(UC). After the UC model was induced by 3% dextran sodium sulfate(DSS), experimental animals were randomly divided into control group, model group, salazosulfapyridine(SASP) group, and low-and high-dose Sishen Pills groups. Drug intervention(ig) was performed for seven consecutive days during modeling. On the 7 th day, the mice were euthanized. The body weight and colon length were recorded, and the histopathological changes of the colon were observed by HE staining. Serum interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and reactive oxygen species(ROS) were detected by ELISA. The protein and mRNA expression of Nrf2, HO-1, and NADPH quinine oxidoreductase-1(NQO-1) was determined by Western blot and reverse transcription-polymerase chain reaction(RT-PCR). Compared with the normal group, the model group exhibited reduced body weight, colon length, and T-AOC, increased IL-6, TNF-α, MDA, and ROS, and diminished protein and mRNA expression of Nrf2, HO-1, and NQO-1 in the colon tissues. Compared with the model group, the SASP group and high-dose Sishen Pills group showed elevated body weight, colon length, and T-AOC, lowered IL-6, TNF-α, MDA, and ROS levels, and increased protein and mRNA expression of Nrf2, HO-1, and NQO-1 in the colon tissues. As assessed by HE staining, Sishen Pills could improve the pathological changes of the colon. The findings suggested that Sishen Pills could protect the colon against UC induced by 3% DSS. The specific mechanism of action may be related to the anti-inflammatory and anti-oxidative stress effects by the activation of the Nrf2/HO-1 signaling pathway.

New protein tyrosine phosphatase inhibitors from fungus Aspergillus gorakhpurensis F07ZB1707.

Twelve new compounds, aspergorakhins A-L (1-12) coupled with one known xanthone leptosphaerin D (13), were isolated from the extract of soil-derived fungus Aspergillus gorakhpurensis F07ZB1707. Their structures were elucidated by spectroscopic data analysis including UV, IR, NMR, and HRESIMS. The absolute configurations of 5 and 8-11 were identified using ECD and OR calculations. All compounds were tested by enzyme inhibitory activity assay in vitro. Aspergorakhin A (1) showed selective activities against PTP1B and SHP1 over TCPTP with IC50 values 0.57, 1.19, and 22.97 µM, respectively. Compounds 1 and 2 exhibited modest cytotoxicity against tumor cell lines A549, HeLa, Bel-7402, and SMMC-7721 with IC50 values in the range of 6.75-83.4 µM.

Corrigendum: MiR-183-5p Promotes Proliferation, Metastasis and Angiogenesis in Breast Cancer Cells through Negatively Regulating Four and a Half LIM Protein 1.

[This corrects the article on p. 355 in vol. 23, PMID: 32908787.].

MiR-183-5p Promotes Proliferation, Metastasis and Angiogenesis in Breast Cancer Cells through Negatively Regulating Four and a Half LIM Protein 1.

PURPOSE: Four and a half LIM protein 1 (FHL1) is involved in breast cancer (BC) development, but the regulatory mechanism involved remain unclear. In the present study, we examined the role of FHL1 in BC development. METHODS: The expression of FHL1, miR-183-5p, and miR-96-5p in BC tissues was analyzed using StarBase analysis. FHL1 expression in BC tissues, a normal human breast epithelial cell line, and BC cell lines was detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The relationship between FHL1 and miR-183-5p/miR-96-5p was analyzed via Pearson's rank correlation, TargetScan, and a dual-luciferase reporter assay. BT549 and MDA-MB-231 cells were transfected with either FHL1 and miR-183-5p mimics, or siFHL1 and a miR-183-5p inhibitor, respectively. The viability, colony number, migration, invasion, and tube length of BT549 and MDA-MB-231 cells were examined using cell counting kit-8, colony formation, wound-healing, Transwell, and tube formation assays, respectively. The levels of FHL1, vascular endothelial growth factor (VEGF), p53, E-cadherin, N-cadherin, and vimentin were quantified using western blotting and qRT-PCR. RESULTS: FHL1 expression was downregulated in BC tissues and cells, whereas miR-183-5p and miR-96-5p were upregulated in BC tissues (negative correlation with FHL1 expression). FHL1 overexpression inhibited the viability, colony number, migration, and invasion of BC cells and the expression of VEGF, N-cadherin, and vimentin, and increased the expression of FHL1, p53, and E-cadherin in BT549 cells. Furthermore, a miR-183-5p mimic reversed these effects of FHL1 overexpression, whereas FHL1 silencing caused opposite results to those observed in MDA-MB-231 cells; however, this was reversed by a miR-183-5p inhibitor. CONCLUSION: Our study suggests that miR-183-5p promotes cell proliferation, metastasis, and angiogenesis by negatively regulating FHL1 in BC.

Migration and transformation of cadmium in rice - soil under different nitrogen sources in polymetallic sulfide mining areas.

We conducted pot experiments to assess the bioavailability of cadmium (Cd) in contaminated rhizosphere soil and accumulation in rice organs in response to nitrogen (N) supply ((NH4)2SO4, NH4NO3, NH4Cl). The results showed that the concentration of bioavailable Cd in rice rhizosphere soil was (NH4)2SO4 treatment > NH4Cl treatment > NH4NO3 treatment at the same level of N application and growth period; the Cd concentration in rice roots was (NH4)2SO4 treatment > NH4NO3 treatment > NH4Cl treatment; and the Cd concentration in rice straw was NH4NO3 treatment > NH4Cl. The Cd concentration in rice roots, straws, and seeds at the maturity stage was (NH4)2SO4 treatment > NH4Cl treatment. With the same N fertilizer, excessive N promoted Cd accumulation in rice at later growth stages. This suggested that sulfate (SO42-) influenced Cd concentration in rice. NH4Cl application maintained a low Cd level in different rice organs with the same N level. This confirmed that NH4Cl is a safe N source for rice planting in polymetallic sulfide mining areas. The study concludes that appropriate NH4Cl levels for Cd-contaminated paddy soil with high-S-content could obtain rice grains with Cd concentrations below the food safety standards (0.2 or 0.4 mg·kg-1).

Long non-coding RNA UCA1 promotes breast cancer by upregulating PTP1B expression via inhibiting miR-206.

BACKGROUND: The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) is involved in various cancers and often functions through microRNAs. The pro-survival protein PTP1B is known to play important roles in cancer development. However, the connection between UCA1 and PTP1B in breast cancer is not well studied. METHODS: In this study, we first evaluated the correlation between UCA1 level and PTP1B expression in breast tissues, which showed the expression of PTP1B were much higher in the breast tumor tissues than in the peritumor normal tissues. The UCA1 level was positively associated with PTP1B expression in breast tumor tissues. RESULTS: We observed that UCA1 could up-regulate PTP1B expression in breast cancer cells. We also found that miR-206 could inhibit the expression of PTP1B by directly binding to the 3'-UTR of its mRNA. Interestingly, UCA1 could increase the expression of PTP1B through sequestering miR-206 at post-transcriptional level. The results also suggested that UCA1-induced PTP1B expression facilitated the proliferation of breast cancer cells. CONCLUSIONS: We conclude that UCA1 can up-regulates PTP1B to enhance cell proliferation through sequestering miR-206 in breast cancer. Our finding provides new insights into the mechanism of breast cancer regulation by UCA1, which could be a potential target for breast cancer treatment.Trial registration 2012N5hSYSU48573. Registered at Oct 12, 2012.

Discovery of naphthacemycins as a novel class of PARP1 inhibitors.

Poly (ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear protein that plays important roles in a variety of nuclear processes, and it has been proved a prominent target in oncology for its key function in DNA damage repair. In this study, we discovered a series of naphthacemycins as a new class of PARP1 inhibitors from a microbial metabolites library via high-throughput screening. Compound I, one of this series of compounds, could reduce cellular poly (ADP-ribose) level, trap PARP1 on the damaged DNA and elevate the level of γ-H2AX, and showed the selective cytotoxicity against BRCA1-deficient cell line. Our study provided a potential scaffold for the development of new PARP1 inhibitors in cancer therapy.

Comparisons of p53, KI67 and BRCA1 expressions in patients with different molecular subtypes of breast cancer and their relationships with pathology and prognosis.

PURPOSE: To compare the expressions of p53, a tumor suppressor gene, KI67, a proliferating cell nuclear antigen, and breast cancer 1 (BRCA1), a breast cancer susceptibility gene, in patients with different molecular subtypes of breast cancer (BC) and investigate their relationships with pathology and prognosis. METHODS: A total of 134 BC postoperative tissue specimens preserved from January 2012 to August 2013 were selected. The expressions of p53, KI67, and BRCA1 in different molecular subtypes of BC were compared, their relationships with pathological features were explored, and the expression correlations among p53, KI67, and BRCA1 were analyzed at the same time. RESULTS: P53 expression was the lowest in Luminal A subtype and similar in human epidermal growth factor receptor 2 (HER-2)-overexpression subtype and triple-negative subtype, with higher expression rates than those in other molecular subtypes. The expression of KI67 was the lowest in Luminal A subtype, showing a significant difference (p<0.05) from that in other molecular subtypes and it was the highest in Luminal B subtype (p<0.05). BRCA1 exhibited the lowest expression in Luminal B-like subtype but the highest expression in Luminal A subtype. The protein expressions of p53 and KI67 were not related to age but correlated with tumor size, histological grade, lymph node metastasis, estrogen receptor (ER)/progesterone receptor (PR) status, and HER-2 status. The expression of p53 was increased with larger tumor size, higher histological grade, presence of lymph node metastasis (n), lower expression of ER/PR, and higher expression of HER-2. BRCA1 expression had no relation with age, tumor size, histological grade, lymph node metastasis (n), ER/PR status, and HER-2 status. A positive correlation was found between p53 and KI67 (r=0.893, p=0.021). There were negative correlations between p53 and BRCA1 (r=-0.921, p=0.011), and between KI67 and BRCA1 (r=-0.821, p=0.032). The median survival time of patients with positive expressions of p53, KI67 and BRCA1 was significantly shorter than those of patients with negative expressions. CONCLUSION: The expressions of p53, KI67 and BRCA1 in different molecular subtypes of BC are evidently different and related to pathological features. The above protein expressions are helpful in predicting the prognosis, diagnosis, and treatment of BC.

Restoration of Arpin suppresses aggressive phenotype of breast cancer cells.

Arpin, a negative regulator of the actin-related protein-2/3 (Arp2/3) complex, is downregulated and predicts poor prognosis in breast cancer patients. However, its biological relevance in breast cancer is still unclear. This study was conducted to investigate the roles of Arpin in breast cancer growth and invasion. We overexpressed Arpin expression in MCF-7 and MDA-MB-231 breast cancer cells and examined the effects of restoration of Arpin on cell proliferation, colony formation, cell cycle distribution, invasion in vitro and tumorigenesis in vivo. The related molecular mechanism(s) was determined. It was found that ectopic expression of Arpin significantly decreased cell proliferation, colony formation, and tumorigenicity. Flow cytometric analysis showed that overexpression of Arpin significantly increased the percentage of G0/G1-phase cells and decreased the percentage of S-phase cells. Moreover, restoration of Arpin impaired the invasiveness of breast cancer cells, as determined by Transwell invasion assays. Mechanistically, overexpression of Arpin inhibited the phosphorylation of Akt in breast cancer cells. Co-expression of a constitutively active form of Akt blunted the suppression of cell proliferation and invasion by Arpin. Taken together, we provide evidence that Arpin acts as a tumor suppressor in breast cancer, which is associated with inhibition of Akt signaling. Restoration of Arpin may represent a promising therapeutic strategy against breast cancer progression.

Discovery of a new structural class of competitive hDHODH inhibitors with in vitro and in vivo anti-inflammatory, immunosuppressive effects.

Human dihydroorotate dehydrogenase (hDHODH) is an inner mitochondrial membrane enzyme that involves in the fourth step of the biosynthesis of pyrimidine base. Inhibitors of hDHODH have been proven efficacy for the treatments of inflammation, rheumatoid arthritis, multiple sclerosis and cancer. In the present study, ascochlorin (ASC) and its derivatives, natural compounds from fungal metabolites, were discovered as hDHODH inhibitors by high-throughput screening. Enzyme kinetics studies showed that ASC competitively binds to hDHODH at the site of coenzyme Q substrate. In ex vivo study, ASC significantly inhibited the ConA-stimulated T lymphocytes proliferation and interleukin-2, interferon-γ production. Furthermore, ASC showed significant in vivo anti-inflammatory and immunosuppressive effects on the mice ears swelling, allogenic skin grafts and rat collagen-induced arthritis animal disease models. ASC significantly reduced ears edema level of mice, increased the survival time of allogenic skin implanted on the mice and attenuated arthritis severity of rat model. In conclusion, ASC was identified as a new structural class of hDHODH inhibitors with efficient anti-inflammatory, immunosuppressive activity, and may be a promising candidate for the development of new therapy in the treatment of autoimmune diseases.

[Coumarins of Anemone raddeana Regel and their biological activity].

To study the coumarins of Anemone raddeana Regel, the compounds were separated by silica gel column chromatography and HPLC. Their structures were identified by their physicochemical property and spectral analysis. Two new compounds were isolated and identified as 4, 7-dimethoxyl-5-methyl-6-hydroxy coumarin (1) and 4, 7-dimethoxyl-5-formyl-6-hydroxycoumarin (2). The bioassays indicated that compounds 1 and 2 could significantly inhibit the proliferation of cancer cell, and showed the agonist effect on the transactivity of retinoic acid receptor-alpha (RARalpha). In addition, the two compounds had inhibitory effect against human leukocyte elastase (HLE).

[Microbial reduction and mobilization of adsorbed arsenate on ferric/aluminum hydroxides].

Although the mechanisms of arsenic release into groundwater remain poorly characterized, microbial reduction of As (V) adsorbed on the surface of iron oxides and the reductive dissolution of iron oxides are generally considered to play a key role in the mobilization of arsenic. We investigated the impact of bacterial reduction of adsorbed As (V) on a Al:Fe (1:0, 1:1, 0:1) hydroxides on arsenic mobilization using the mixed bacterial culture. After inoculation, the increase of dissolved As (III) concentration was observed, whereas As (V) was negligible in aqueous phase. Arenic release for the Al:Fe (1:0, 1:1, 0:1) hydroxides systems was 60 microg/L, 1.3 mg/L and 7.8 mg/L respectively. On the contrary, neither reduction nor release of arsenic was observed in the uninoculated groups. Furthermore, the introduction of aluminium may be responsible for the release of arsenic owing to its weaker affinity to As (III). In addition, our results showed that Fe reduction occurred far later than arsenic reduction and mobilization and obvious increase was not observed even after Fe reduction occurred. It suggested that in natural systems, the biotic reduction of As (V) adsorbed on ferric oxides or Fe (III) may not the major cause of arsenic release in sediment or groundwater system as previous works proposed. The reduction of As (V) bound to aluminum oxides or other minerals may play a key role.