Based on metabolomics, the optimum wind speed process parameters of flue-cured tobacco in heat pump bulk curing barn were explored.

To explore the influence of wind speed on the quality of tobacco in this study, we employed a heat pump-powered intensive curing barn and a three-stage curing process. By evaluating the influence of fan parameters on the quality of tobacco leaves at different curing stages, the optimal wind speed was determined. After adopting the optimized wind speed process, the degradation of macromolecular substances was faster, the accumulation of aroma substances was delayed to 55 °C, and the accumulation was more complete. Among them, the contents of reducing sugar and total sugar in flue-cured tobacco leaves were 22.25% and 29.2%, respectively, which were lower than those in the control group. The sugar was converted into more aroma substances, and the total amount of neutral aroma substances was 48.82% higher than that of the control group. The content of related aroma substances increased significantly. The content of petroleum ether extract related to aroma substances increased by 0.93% compared with the control group. The macromolecular substances were degraded more fully than the control group, such as the starch content decreased to 1.56%. The results of metabolomics showed that the contents of aldehydes, heterocyclic compounds, alcohols, ketones and esters increased significantly in different degrees after this process. These results show that the optimization of wind speed parameters can significantly improve the baking quality of tobacco leaves. This study provides a reference for the optimization of the flue-cured tobacco baking process.

ANP32B-mediated repression of p53 contributes to maintenance of normal and CML stem cells.

Proper regulation of p53 signaling is critical for the maintenance of hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs). The hematopoietic cell-specific mechanisms regulating p53 activity remain largely unknown. Here, we demonstrate that conditional deletion of acidic leucine-rich nuclear phosphoprotein 32B (ANP32B) in hematopoietic cells impairs repopulation capacity and postinjury regeneration of HSCs. Mechanistically, ANP32B forms a repressive complex with p53 and thus inhibits the transcriptional activity of p53 in hematopoietic cells, and p53 deletion rescues the functional defect in Anp32b-deficient HSCs. Of great interest, ANP32B is highly expressed in leukemic cells from patients with chronic myelogenous leukemia (CML). Anp32b deletion enhances p53 transcriptional activity to impair LSC function in a murine CML model and exhibits synergistic therapeutic effects with tyrosine kinase inhibitors in inhibiting CML propagation. In summary, our findings provide a novel strategy to enhance p53 activity in LSCs by inhibiting ANP32B and identify ANP32B as a potential therapeutic target in treating CML.

FBXO22 mediates polyubiquitination and inactivation of LKB1 to promote lung cancer cell growth.

Liver kinase B1 (LKB1) regulates both cell growth and energy metabolism. Inactivated mutations of LKB1, observed in 20-30% of nonsmall cell lung cancers (NSCLC), contribute significantly to lung cancer malignancy progression. However, the upstream signalings regulating LKB1 activity remain incompletely understood. Here, we present evidence that FBXO22 interacts with and promotes polyubiquitination of LKB1. More intriguingly, FBXO22 mediates Lys-63-linked LKB1 polyubiquitination and inhibits kinase activity of LKB1. Furthermore, over-expression of FBXO22 promotes NSCLC cell growth through inhibiting LKB1-AMPK-mTOR signaling in vitro and in vivo. Clinically, FBXO22 is highly expressed in human lung adenocarcinoma and high FBXO22 expression predicts significant poor prognosis. Our study provides new insights into the upstream regulation of LKB1 activation and identifies FBXO22 as a potential therapeutic target for lung cancer treatment.

Treponema pallidum promotes macrophage polarization and activates the NLRP3 inflammasome pathway to induce interleukin-1ß production.

BACKGROUND: The involvement of inflammasome activation and macrophage polarization during the process of syphilis infection remains unknown. In this study, A series of experiments were performed using human macrophages to research the role of NLRP3 inflammasome regulation in interleukin (IL)-1ß production and its influence on macrophage polarization triggered by T. pallidum. RESULTS: The results showed that in M0 macrophages treated with T. pallidum, the M1-associated markers inducible nitric oxide synthase (iNOS), IL-1ß and TNF-α were upregulated, and the M2-associated markers CD206 and IL-10 were downregulated. In addition, we observed NLRP3 inflammasome activation and IL-1ß secretion in T. pallidum-treated macrophages, and the observed production of IL-1ß occurred in a dose- and time-dependent manner. Moreover, the secretion of IL-1ß by macrophages after T. pallidum treatment was notably reduced by anti-NLRP3 siRNA and caspase-1 inhibitor treatment. NAC, KCl, and CA074-ME treatment also suppressed IL-1ß release from T. pallidum-treated macrophages. CONCLUSIONS: These findings showed that T. pallidum induces M0 macrophages to undergo M1 macrophage polarization and elevate IL-1ß secretion through NLRP3. Moreover, the process of NLRP3 inflammasome activation and IL-1ß production in macrophages in response to T. pallidum infection involves K+ efflux, mitochondrial ROS production and cathepsin release. This study provides a new insight into the innate immune response to T. pallidum infection.

Akt, mTOR and NF-κB pathway activation in Treponema pallidum stimulates M1 macrophages.

The polarization of macrophages and the molecular mechanism involved during the early process of syphilis infection remain unknown. This study was conducted to explore the influence of Treponema pallidum (T. pallidum) treatment on macrophage polarization and the Akt-mTOR-NFκB signaling pathway mechanism involved in this process. M0 macrophages derived from the phorbol-12-myristate-13-acetate-induced human acute monocytic leukemia cell line THP-1 were cultured with T. pallidum. T. pallidum induced inflammatory cytokine (IL-1ß and TNF-α) expression in a dose- and time-dependent manner. However IL-10 cytokine expression decreased at the mRNA and protein levels. Additionally, the expression of the M1 surface marker iNOS was up-regulated with incubation time, and the expression of the M2 surface marker CD206 was low (vs. PBS treated macrophages, P < 0.001) and did not fluctuate over 12 h. Further studies revealed that Akt-mTOR-NFκB pathway proteins, including p-Akt, p-mTOR, p-S6, p-p65, and p-IκBα, were significantly higher in the T. pallidum-treated macrophages than in the PBS-treated macrophages (P < 0.05). In addition, inflammatory cytokine expression was suppressed in T. pallidum-induced M1 macrophages pretreated with LY294002 (an Akt-specific inhibitor) or PDTC (an NF-κB inhibitor), while inflammatory cytokine levels increased in T. pallidum-induced M1 macrophages pretreated with rapamycin (an mTOR inhibitor). These findings revealed that T. pallidum promotes the macrophage transition to pro-inflammatory M1 macrophages in vitro. The present study also provides evidence that Akt, mTOR and NF-κB pathway activation in T. pallidum stimulates M1 macrophages. This study provides novel insights into the innate immune response to T. pallidum infection.

Development of tissue inflammation accompanied by NLRP3 inflammasome activation in rabbits infected with Treponema pallidum strain Nichols.

BACKGROUND: The inflammasome responses in Treponema pallidum infection have been poorly understood to date. This study aimed to investigate the expression of the nucleotide-binding leucine-rich receptor protein 3 (NLRP3) inflammasome in the development of tissue inflammation in rabbits infected with T. pallidum. METHODS: Forty-five rabbits were randomly assigned to a blank group or an infection group, and the latter was divided into no benzathine penicillin G (BPG) and BPG treatment subgroups. Rabbits in the infection group were injected intradermally with 0.1 mL of a 107/mL T. pallidum suspension at 10 marked sites along the back, and the blank group was treated with normal saline. The BPG treatment subgroup received 200,000 U of BPG administered intramuscularly twice, at 14 d and 21 d post-infection. The development of lesions was observed, and biopsies of the injection site and various organs, including the kidney, liver, spleen, lung, and testis, were obtained for NLRP3, caspase-1, and interleukin-1ß (IL-1ß) mRNA analysis during infection. Blood was also collected for the determination of IL-1ß concentration. RESULTS: Rabbits infected with T. pallidum (both the BPG treatment and no BPG treatment subgroups), exhibited NLRP3 inflammasome activation and IL-1ß secretion in cutaneous lesions, showing a trend in elevation to decline; NLRP3 mRNA expression reached a peak at 18 d in the BPG treatment subgroup and 21 d in the no BPG treatment subgroup and returned to "normal" levels [vs. the blank group (P > 0.05)] at 42 d post-infection. The trend was similar to the change in cutaneous lesions in the infected rabbits, which reached a peak at 16 d in the BPG treatment subgroup and 18 d in the no BPG treatment subgroup. NLRP3, caspase-1, and IL-1ß mRNA expression levels were slightly different in different organs. NLRP3 inflammasome activation was also observed in the kidney, liver, lung, spleen and testis. IL-1ß expression was observed in the kidney, liver, lung and spleen; however, there was no detectable level of IL-1ß in the testes of the infected rabbits. CONCLUSIONS: This study established a clear link between NLRP3 inflammasome activation and the development of tissue inflammation in rabbits infected with T. pallidum. BPG therapy imperceptibly adjusted syphilitic inflammation.

Dicer1 dysfunction promotes stemness and aggression in endometrial carcinoma.

Endometrial carcinoma is one of the most common gynecological malignancies, but the molecular events involved in the development and progression of endometrial carcinoma remain unclear. Dicer1 and cancer stem cells play important roles in cell motility and survival. This study investigated the role of the let-7 family and Dicer1 in the stemness of endometrial carcinoma cells. We profiled Dicer1 expression in clinical samples and explored its relationship with stem cell-associated markers and clinical parameters. We showed that Dicer1 dysfunction leads to the enrichment of tumor stemness features and tumor aggression both in vitro and in vivo. We also identified the mechanism related to this potential tumor-predisposing phenotype: loss of Dicer1 induced abnormal expression of the let-7 family, which comprises well-known tumor suppressors, thus regulating stemness in endometrial carcinoma cells.

Thoracic Vertebral Hemangioma with Spinal Cord Compression: Multidisciplinary Surgical Treatment and Follow-up of Six Patients.

OBJECTIVE: To provide useful insights of multidisciplinary surgical treatment for vertebral hemangioma with spinal cord compression. METHODS: From 2009 to 2014, data on six patients who were diagnosed with cord compression vertebral hemangioma were reviewed and analyzed retrospectively. There were five women and one man with a mean age of 48.6 years (range, 26-68 years). All the patients were treated by multidisciplinary approach, including use of gelfoam, pedicle screw instrumentation, vertebroplasty, and decompression laminectomy. Neurological status and Frankel grades were documented, CT scan and MRI were performed after surgery. RESULTS: The follow-up period ranged from 8 to 54 months. Mean blood loss was around 367 mL, and the mean surgical time was 2.30 h. All patients had uneventful intraoperative and postoperative courses and reported symptomatic and neurological relief to varying degrees, at an average follow-up period of 23 months. Bone cement distribution was disseminated homogeneously over the affected vertebra and no leakage was observed. All the patients had a complete restoration to Frankel grade E. The postoperative and follow-up imaging showed that the implant was in perfect position, and no recurrence occurred in all patients. CONCLUSION: The vertebral hemangioma with cord compression is a challenge to surgeons for therapeutic improvement, and an active involvement of several disciplines as well as performance of multidisciplinary surgical treatment can be crucial in achieving favorable results.

Clinical and Radiographic Results of Reconstruction with Fibular Autograft for Distal Radius Giant Cell Tumor.

OBJECTIVE: To evaluate the result of en bloc resection and reconstruction of the distal radius with a non-vascularized fibular autograft for giant cell tumor (GCT) of bone. METHODS: Between 2005 and 2015, 12 eligible patients (seven males, five females, mean age 31.3 years) with grade III GCT of the distal radius were treated by en bloc resection and reconstruction with non-vascularized proximal fibular autografts in four Chinese institutions (members of Giant Cell Tumor Team of China). The patients had a clinical and radiographic review every 6 months for the first 2 years then annually thereafter. The functional, oncologic and radiological outcomes of the patients were analyzed. RESULTS: The mean duration of follow-up was 39.6 months. Bony union was achieved in all cases. None of the patients were dissatisfied with the shape and appearance of the wrist. The mean MSTS score was 25.23 ± 2.38 (range, 22-29). The mean DASH score was 13.0 (range, 6.7-33.3). The average range of motion of the wrist was: 35.8° ± 14.5° of extension, 14.0° ± 8.4° of flexion, 15.5° ± 6.7° of radial deviation, 19.4° ± 10.1° of ulnar deviation, 57.2° ±18.9° of pronation and 44.0° ± 24.8° of supination. The average percentage of grip strength was 55.2% ± 29.0% compared with that of the contralateral side. One localized soft tissue recurrence occurred; it was successfully managed by excision. Lung metastases developed postoperatively in one case and were treated by gamma knife radiotherapy. There was radiographic evidence of radiocarpal arthritis in eleven patients, bone resorption in ten, distal radioulnar joint diastasis in six, ulnar deviation of the wrist in seven, subluxation of the carpal bone in three and dislocation of the carpal bone in one patient. CONCLUSIONS: Reconstruction with a non-vascularized proximal fibular autograft is a reasonable option after en bloc resection of the distal radius for giant cell tumor of bone.

Limb Salvage by Distraction Osteogenesis for Distal Tibial Osteosarcoma in a Young Child: A Case Report.

Under the effective chemotherapy protocol, physeal distraction could be used as an effective limb salvage in the growing children with lower-limb malignant metaphyseal bone tumours and could actively prevent leg length discrepancy or malalignment that profoundly affects function. In this paper, we report a 7-year-old boy with right distal tibial osteosarcoma but not yet invaded the epiphysis, which underwent surgical treatment after effective chemotherapy. The surgical procedure included two phases: epiphysiolysis (physeal distraction) and en-bloc resection of tumor and distraction osteogenesis. In the first phase, after osteotomy of the proximal fibula was performed, two Ilizarov rings were attached to the proximal tibia and one Ilizarov ring was applied to the distal tibia. At same time, U-shape ring as an important external fixator was been used in the axis of rotation of the ankle joint in order to balance the stress from the surrounding tissues, increase distracting stabilization and prevent the deformity or contracture of ankle joint. In the second phase, the tumor bone (5.7 cm) was en bloc resected by diaphyseal osteotomy. Distraction osteogenesis was commenced 1 week postoperatively at a rate of 1 mm twice a day. The patient was reviewed by X-ray intermittently. The new bone was formed and the entire bone defect was covered in four months after the operation. Doxorubicin and cisplatin as the neoadjuvant chemotherapy protocol are effective to osteosarcoma and chemotherapy process did not adversely affect the union. Through this technique, the right distal tibial epiphysis was reserved successfully. At the last follow-up, there are no local recurrence or metastasis and we achieve to prevent leg length discrepancy or malalignment that profoundly affects function.

Mutant p53 induces EZH2 expression and promotes epithelial-mesenchymal transition by disrupting p68-Drosha complex assembly and attenuating miR-26a processing.

The tumor suppressor p53 and the transcriptional repressor Enhancer of Zeste Homolog 2 (EZH2) have both been implicated in the regulation of epithelial-mesenchymal transition (EMT) and tumor metastasis via their impacts on microRNA expression. Here, we report that mutant p53 (mutp53) promotes EMT in endometrial carcinoma (EC) by disrupting p68-Drosha complex assembly. Overexpression of mutp53 has the opposite effect of wild-type p53 (WTp53), repressing miR-26a expression by reducing pri-miR-26a-1 processing in p53-null EC cells. Re-expression of miR-26a in mutp53 EC cells decreases cell invasion and promotes mesenchymal-epithelial transition (MET). Rescuing miR-26a expression also inhibits EZH2, N-cadherin, Vimentin, and Snail expression and induces E-cadherin expression both in vitro and in vivo. Moreover, patients with higher serum miR-26a levels have a better survival rate. These results suggest that p53 gain-of-function mutations accelerate EC tumor progression and metastasis by interfering with Drosha and p68 binding and pri-miR-26a-1 processing, resulting in reduced miR-26a expression and EZH2 overexpression.

The role of the globular heads of the C1q receptor in HPV-16 E2-induced human cervical squamous carcinoma cell apoptosis via a mitochondria-dependent pathway.

BACKGROUND: Human papillomavirus type-16 (HPV-16) E2 protein acts as a transcriptional modulator and plays a key role in regulating many biological responses. The purpose of this study was to investigate the relationship between HPV-16 E2, the receptor for the globular heads of human C1q (gC1qR) gene expression, mitochondrial dysfunction and apoptosis regulation in human cervical squamous carcinoma cells (C33a and SiHa). METHODS: HPV-16 E2 and gC1qR expression was examined using real-time PCR and western blot analysis. Apoptosis in C33a and SiHa cells was assessed by flow cytometry. Mitochondrial function was detected via ROS generation, the amount of cytosolic Ca2+, and changes in the mitochondrial membrane potential (Δψm). RESULTS: The expression of the HPV-16 E2 and gC1qR gene significantly decreased in human cervical squamous carcinoma samples relative to the non-cancerous cervix samples. C33a and SiHa cells that were transfected with a vector encoding HPV-16 E2 displayed significantly increased gC1qR gene expression and mitochondrial dysfunction as well as an up-regulation of cellular apoptosis, which was abrogated by the addition of gC1qR small-interfering RNA (siRNA). CONCLUSIONS: These data support a mechanism whereby gC1qR plays an important role in HPV-16 E2-induced human cervical squamous carcinoma cell apoptosis via a mitochondria-dependent pathway.

Expression, SNV identification, linkage disequilibrium, and combined genotype association analysis of the muscle-specific gene CSRP3 in Chinese cattle.

The cysteine and glycine-rich protein 3 (CSRP3) plays an important role in the myofiber differentiation. Here, we identified five SNVs in all exon and intron regions of the CSRP3 gene using DNA sequencing, PCR-RFLP and forced-PCR-RFLP methods in 554 cattle. Four of the five SNVs were significantly associated with growth performance and carcass traits of the cattle. In addition, we evaluated haplotype frequency and linkage disequilibrium coefficient of five sequence variants. The result of haplotype analysis demonstrated 28 haplotypes present in Qinchuan and two haplotypes in Chinese Holstein. Only haplotypes 1 and 8 were being shared by two populations, haplotype 14 had the highest haplotype frequency in Qinchuan (17.4%) and haplotype 8 had the highest haplotype frequency in Chinese Holstein (94.4%). Statistical analyses of combined genotypes indicated that some combined genotypes were significantly or highly significantly associated with growth and carcass traits in the Qinchuan cattle population. qPCR analyses also showed that bovine CSRP3 gene was exclusively expressed in longissimus dorsi muscle and heart tissues. The data support the high potential of the CSRP3 as a marker gene for the improvement of growth performance and carcass traits in selection programs.

SNV and haplotype analysis reveals new CSRP1 variants associated with growth and carcass traits.

The cysteine and glycine-rich protein 1 and 2 genes (CSRP1 and CSRP2) are an effective growth factor in promoting skeletal muscle growth in vitro and vivo. However, in cattle, the information on the CSRP1 and CSRP2 genes is very limited. The aim of this study was to examine the association of the CSRP1 and CSRP2 variants with growth and carcass traits in cattle breeds. Three single nucleotide variants (SNVs) were identified within the bovine CSRP1 gene, whereas CSRP2 gene has not detected any SNVs, using DNA pooled sequencing, PCR-RFLP, and forced PCR-RFLP methods. These SNVs include g. 801T>C (Intron 2), g. 46T>C (Exon 3) and g. 99C>G (Intron 3). Besides, we also investigated haplotype frequencies and linkage disequilibrium (LD) coefficients for three SNVs in all study populations. LD and haplotype structure of CSRP1 were different between breeds. The result of haplotype analysis demonstrated eight haplotype present in QC (Qinchuan) and one haplotype in CH (Chinese Holstein). Only haplotype 1 (TTC), shared by all two populations, comprised 10.74% and 100.00%, of all haplotypes observed in QC and CH, respectively. Haplotype 5 (CTC) had the highest haplotype frequencies in QC (30.98%) and haplotype 1 had the highest haplotype frequencies in CH (100.00%). The statistical analyses indicated that one single SNV and 19 combined haplotypes were significantly or highly significantly associated with growth and carcass traits in the QC cattle population (P<0.05 or P<0.01). Quantitative real-time PCR (qRT-PCR) analyses showed that the bovine CSRP1 and CSRP2 genes were widely expressed in many tissues. The results of this study suggest that the CSRP1 gene possibly is a strong candidate gene that affects growth and carcass traits in the Chinese beef cattle breeding.

Significantly upregulated TACSTD2 and Cyclin D1 correlate with poor prognosis of invasive ductal breast cancer.

The tumor-associated calcium signal transducer 2 (TACSTD2) gene has been reported to be highly expressed in many types of human epithelial cancers, and is associated with tumor metastasis and poor prognosis. The aims of the present investigation were to analyze the TACSTD2 and Cyclin D1 expression at the mRNA and protein levels and to assess its prognostic significance in invasive ductal breast cancer (IDC). The expressions of TACSTD2 and Cyclin D1 in IDC tissues were consistently higher than those in the tumor-adjacent non-malignant tissues by a one-step real-time polymerase chain reaction and immunohistochemistry (P<0.001 and P=0.023, respectively). The statistical analysis of clinicopathologic characteristics and immunohistochemistry by the χ(2) test showed that the high expression of TACSTD2 in IDC was correlated to histological grade (P=0.023), P53 status (P=0.042), Cyclin D1 status (P<0.001), lymph node metastasis (P<0.001), distant metastasis (P=0.004) and TNM staging (P<0.001). Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of IDC. These analyses also showed that a high TACSTD2 expression (P=0.003), a high Cyclin D1 expression (P=0.041), and lymph node metastasis (P=0.006) were independent prognosis factors. Collectively, our studies demonstrated that the high expression of TACSTD2 correlates with a poor prognosis in IDC.

Pharmacokinetics and pharmacodynamics of single and multiple doses of prasugrel in healthy native Chinese subjects.

AIM: To characterize the pharmacokinetics (PKs), pharmacodynamics (PDs), and tolerability of different dose regimens of prasugrel in healthy Chinese subjects. METHODS: This was a single-centered, open-label, parallel-design study. Subjects received a single loading dose (LD) of prasugrel followed by once-daily maintenance dose (MD) for 10 d. They were enrolled into 3 groups: 60 mg LD/10 mg MD; 30 mg LD/7.5 mg MD; 30 mg LD/5 mg MD. Blood samples were collected after the first and last dose. The serum concentration of the active metabolite of prasugrel was determined using a LC/MS/MS method. Platelet aggregation was assessed using the VerifyNow-P2Y(12) assay. RESULTS: Thirty-six healthy native Chinese subjects (19 males) aged 18-45 were enrolled; mean age and body weight were similar across the treatment groups (n=12 for each). The metabolite AUC(0-4) and C(max) increased dose-proportionally across the dose range of 5 mg to 60 mg. The median T(max) was 0.5 h in all groups. The PD parameters, indicated by the inhibition of ADP-induced platelet aggregation, were met more rapidly in the 60 mg group than the 30 mg group after the LD (94%-98%). This high degree of inhibition of platelet aggregation was maintained following the 10 mg MD (87%-90%) and was lower in the 7.5 mg and 5 mg MD groups (79%-83% and 64%-67%, respectively). Prasugrel was well tolerated in healthy Chinese subjects for single doses up to 60 mg and a MD of 10 mg for 10 d. CONCLUSION: The PKs and PDs of the active metabolite of prasugrel were similar to those in Chinese subjects reported by a previous bridging study, which demonstrated that the exposure to the active metabolite in Chinese subjects was higher than in Caucasians.

Characteristic gene expression profiles in the progression from liver cirrhosis to carcinoma induced by diethylnitrosamine in a rat model.

BACKGROUND: Liver cancer is a heterogeneous disease in terms of etiology, biologic and clinical behavior. Very little is known about how many genes concur at the molecular level of tumor development, progression and aggressiveness. To explore the key genes involved in the development of liver cancer, we established a rat model induced by diethylnitrosamine to investigate the gene expression profiles of liver tissues during the transition to cirrhosis and carcinoma. METHODS: A rat model of liver cancer induced by diethylnitrosamine was established. The cirrhotic tissue, the dysplasia nodules, the early cancerous nodules and the cancerous nodules from the rats with lung metastasis were chosen to compare with liver tissue of normal rats to investigate the differential expression genes between them. Affymetrix GeneChip Rat 230 2.0 arrays were used throughout. The real-time quantity PCR was used to verify the expression of some differential expression genes in tissues. RESULTS: The pathological changes that occurred in the livers of diethylnitrosamine-treated rats included non-specific injury, fibrosis and cirrhosis, dysplastic nodules, early cancerous nodules and metastasis. There are 349 upregulated and 345 downregulated genes sharing among the above chosen tissues when compared with liver tissue of normal rats. The deregulated genes play various roles in diverse processes such as metabolism, transport, cell proliferation, apoptosis, cell adhesion, angiogenesis and so on. Among which, 41 upregulated and 27 downregulated genes are associated with inflammatory response, immune response and oxidative stress. Twenty-four genes associated with glutathione metabolism majorly participating oxidative stress were deregulated in the development of liver cancer. There were 19 members belong to CYP450 family downregulated, except CYP2C40 upregulated. CONCLUSION: In this study, we provide the global gene expression profiles during the development and progression of liver cancer in rats. The data obtained from the gene expression profiles will allow us to acquire insights into the molecular mechanisms of hepatocarcinogenesis and identify specific genes (or gene products) that can be used for early molecular diagnosis, risk analysis, prognosis prediction, and development of new therapies.

Prostaglandin A1 inhibits increases in intracellular calcium concentration, TXA(2) production and platelet activation.

AIM: In our previous studies we found that cyclopentenane prostaglandin A1 (PGA1) had neuroprotective effects in a rodent ischemic model. In the present study we aimed to investigate the inhibitory effect of PGA1 on platelet function. METHOD: The rate of aggregation of human platelets was measured by using turbidimetry. The rate of adhesion of platelets to cultured endothelial cells was determined by using [(3)H]-adenine labeled platelets. 5-Hydroxytryptamine release from platelets was measured with O-phthaldialdehyde fluorospectrophotometry. The levels of TXB(2), a stable metabolite of TXA(2), were determined by radioimmuno-assay. Alternations in platelet morphology were observed using an electron microscope, and the intraplatelet free calcium concentrations were measured with Fluo-3/AM FCM assay. RESULTS: PGA1 significantly inhibited thrombin-, collagen- and ADP-induced aggregation and adhesion of platelets. The morphological changes of platelets induced by thrombin were blocked by PGA1. PGA1 inhibited the release of 5-hydroxytyptamine from dense granules and the synthesis of TXA(2). CONCLUSION: PGA1 inhibits the activation of platelets probably through blocking increases in intracellular calcium concentration and TXA(2) synthesis.