Midterm Outcomes of Endovascular Therapy for TASC II D Femoropopliteal Lesions with Critical Limb Ischemia: A Retrospective Analysis.

BACKGROUND: This study evaluated the midterm results of endovascular therapy (EVT) for Trans-Atlantic Inter-Society (TASC) II D femoropopliteal lesions in patients with critical limb ischemia (CLI). METHODS: Fifty seven limbs of 54 patients with CLI due to TASC II D femoropopliteal lesions who underwent EVT at the First Hospital of Hebei Medical University were retrospectively analysed in a single-centre, observational study. The patient characteristics, endovascular procedural details, freedom from target lesion revascularization (TLR), patency rates, ulcer healing rate, and limb salvage rate were accessed. RESULTS: The patients' mean age was 68.2 ± 8.2 years. All patients were treated by EVT. The final technical success rate was 98.2% (56/57). There were 23 cases of pain at rest, 18 cases of ulcer, and 15 cases of gangrene. The median length of the treated segment was 286 ± 42 mm (56/56) and the mean number of stents placed per patient was 2.0 ± 0.8 (49/56). The postoperative ankle-brachial index was significantly higher than that of the preoperative ankle-brachial index (P < 0.05). The perioperative complication rate was 10.7% (6/56). The restenosis or occlusion rate was 44.6% (25/56). The estimated rates of freedom from TLR at 1 year, 2 years, and 3 years were 86.8%, 67.0%, and 62.5%, respectively. A univariate analysis showed that predictors of freedom from TLR were the number of runoff vessels, length of the lesion, and complexity of the lesion, while predictors for restenosis or occlusion were the length and the complexity of the lesion. The ulcer healing rate was 93.8%. The limb salvage rates were 76.4%, 74.4%, and 70.9% at 1, 2, and 3 years after treatment, respectively. CONCLUSIONS: The midterm outcomes of EVT for TASC II D femoropopliteal lesions in patients with CLI indicated that this treatment approach is safe and effective and is clinically applicable.

Structural characterization and immunoregulatory activity of a neutral polysaccharide from the roots of Apocynum venetum L.

The structural characteristics and immunoregulatory activities of neutral heteropolysaccharide (AVRP-N) separated from the roots of Apocynum venetum L. were extensively investigated. The results showed that the weight average molecular mass (Mw) of AVRP-N was 6.430 × 103 Da. Moreover, the backbone is composed of natural acetylated (1 â†’ 4)-ß-D-Man and (1 â†’ 5)-α-L-Ara domains. The mannan is composed of →4)-ß-D-Manp-(1→, →4)-ß-D-Glcp-(1→, and the terminal group α-D-Galp-(1→ attached to →4,6)-ß-D-Manp-(1→ at O-6. Araban is composed of →5)-α-L-Araf-(1→; the terminal group α-L-Araf-(1→attached to→2,3,5)-α-L-Araf-(1→ at O-2, O-3 and →3,5)-α-L-Araf-(1→ at O-3. In addition, the senior structure shows that AVRP-N has a triple-helix conformation. Furthermore, AVRP-N exhibited immunomodulatory effects, which could significantly regulate the proliferation of mouse splenic lymphocytes by enhancing the secretion of the cytokines (IFN-γ, IL-2, IL-4, and IL-10). Our results provide new structural and immunoregulatory information for natural polysaccharides derived from Apocynum venetum L.

Immunomodulatory effects of flazin from Crassostrea sikamea on splenic lymphocytes of Sprague-Dawley rats.

Crassostrea sikamea (C.sikamea) is an important edible and medicinal seafood in China. In the present study, a compound named flazin was separated and identified from the ethyl acetate extract of C.sikamea (EAECs) for the first time. In addition, the 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetra zolium (MTS) assay revealed that EAECs and flazin inhibited the transformation of splenic lymphocytes in vitro. Moreover, flazin (20 µg·mL-1) altered the populations of splenic lymphocyte subtypes. Real-time quantitative PCR (RT-qPCR) analysis and enzyme-linked immunosorbent assay (ELISA) showed that flazin suppressed the mRNA expression and secretion of TNF-α and IL-2, and reversed Concanavalin A (ConA)-induced mRNA up-regulation and protein secretion of TNF-α and IL-2. Western blot results showed that flazin reversed ConA-induced increases in p-ERK1/2 and p-p38 in splenocytes. In conclusion, flazin exhibits effective immunomodulatory function and may be useful for treating immune-related disorders, which indicates the application potential of C.sikamea as a functional food or immunomodulator.

Tectorigenin enhances PDX1 expression and protects pancreatic ß-cells by activating ERK and reducing ER stress.

Pancreas/duodenum homeobox protein 1 (PDX1) is an important transcription factor that regulates islet ß-cell proliferation, differentiation, and function. Reduced expression of PDX1 is thought to contribute to ß-cell loss and dysfunction in diabetes. Thus, promoting PDX1 expression can be an effective strategy to preserve ß-cell mass and function. Previously, we established a PDX1 promoter-dependent luciferase system to screen agents that can promote PDX1 expression. Natural compound tectorigenin (TG) was identified as a promising candidate that could enhance the activity of the promoter for the PDX1 gene. In this study, we first demonstrated that TG could promote the expression of PDX1 in ß-cells via activating extracellular signal-related kinase (ERK), as indicated by increased phosphorylation of ERK; this effect was observed under either normal or glucotoxic/lipotoxic conditions. We then found that TG could suppress induced apoptosis and improved the viability of ß-cells under glucotoxicity and lipotoxicity by activation of ERK and reduction of reactive oxygen species and endoplasmic reticulum (ER) stress. These effects held true in vivo as well: prophylactic or therapeutic use of TG could obviously inhibit ER stress and decrease islet ß-cell apoptosis in the pancreas of mice given a high-fat/high-sucrose diet (HFHSD), thus dramatically maintaining or restoring ß-cell mass and islet size, respectively. Accordingly, both prophylactic and therapeutic use of TG improved HFHSD-impaired glucose metabolism in mice, as evidenced by ameliorating hyperglycemia and glucose intolerance. Taken together, TG, as an agent promoting PDX1 expression exhibits strong protective effects on islet ß-cells both in vitro and in vivo.

Association of p53 expression with poor prognosis in patients with triple-negative breast invasive ductal carcinoma.

TP53 gene is mutated in approximately 80% of triple-negative breast cancer (TNBC). However, the prognostic significance of immunohistochemical (IHC)-detected p53 protein expression remains controversial in TNBC. In this study, we retrospectively analyzed the association between IHC-detected p53 expression and the prognosis in a cohort of 278 patients with stage I-III triple-negative breast invasive ductal carcinoma (IDC), who received surgery at the department of breast surgery in the Fourth Hospital of Hebei Medical University from 2010-01 to 2012-12. We found a positive expression ratio of IHC-detected p53 in triple-negative breast IDC of 58.6% (163/278). Furthermore, levels of expression were significantly associated with vessel tumor emboli and higher histologic grade (P = .038, P = .043, respectively), with the highest expression level observed in G3 breast cancer (64.7%). Additionally, Kaplan-Meier analysis showed that p53 expression indicated worse overall survival (OS) in the whole cohort (79.6% vs 89.6%, Log-rank test P = .025) as well as in stratified prognostic stage II patients (90.8% vs 100%, Log-rank test P = .027). The mortality risk of p53 expression patients was 2.22 times higher than that of p53 negative patients (HR: 2.222; 95%CI: 1.147-4.308). In addition, p53 expression was also associated with poor disease-free survival (DFS) (76.7% vs 86.8%, P = .020). Cox proportional hazard ratio model showed p53 expression was an independent risk factor for OS (P = .018) and DFS (P = .018) after controlling for tumor size, lymph node status, and vessel tumor emboli. Altogether, our data showed that IHC-detected p53 expression is a promising prognostic candidate for poor survival in triple-negative breast IDC patients. However, more studies are needed to determine if p53 may be applied to clinical practice as a biomarker and/or novel therapeutic target for TNBC.

Impact of Smoking on Anal Abscess and Anal Fistula Diseases.

BACKGROUND: Several studies have investigated the association between smoking and anal abscess and anal fistula (AA/F) diseases. However, the relationship between cigarette smoking and AA/F remains unclear. This study sought to assess the role of smoking in anorectal male patients in a Chinese population. METHODS: In this retrospective study, a questionnaire, including smoking history, was completed over a 3-month period by male inpatients in the Proctology Department of China-Japan Friendship Hospital. "Cases" were patients who had AA/F, and "controls" were patients with other anorectal complaints. Mann-Whitney U-test and Chi-square test were carried out to examine differences in baseline characteristics between groups. Subsequently, multivariate logistic regression was used to explore any related factors. RESULTS: A total of 977 patients aged from 18 to 80 years were included, excluding those diagnosed with inflammatory bowel disease or diabetes mellitus. Out of this total, 805 patients (82.4%) completed the entire questionnaire. Among the 805 patients, 334 (41.5%) were cases and 471 (58.5%) were controls. Results showed significant differences between cases and controls (χ2 = 205.2, P < 0.001), with smoking found to be associated with the development of AA/F diseases (odds ratio: 12.331, 95% confidence interval: 8.364-18.179, P < 0.001). CONCLUSIONS: This study suggested smoking to be a potential risk factor for the development of AA/F diseases in a Chinese population. Consequently, current smoking patients should be informed of this relationship, and further research should be conducted to explore and investigate this further.

Virtual screening and experimental validation of novel histone deacetylase inhibitors.

BACKGROUND: Histone deacetylases (HDACs) are promising therapeutic targets for the treatment of cancer, diabetes and other human diseases. HDAC inhibitors, as a new class of potential therapeutic agents, have attracted a great deal of interest for both research and clinical applications. Increasing efforts have been focused on the discovery of HDAC inhibitors and some HDAC inhibitors have been approved for use in cancer therapy. However, most HDAC inhibitors, including the clinically approved agents, do not selectively inhibit the deacetylase activity of class I and II HDAC isforms, and many suffer from metabolic instability. This study aims to identify new HDAC inhibitors by using a high-throughput virtual screening approach. METHODS: An integration of in silico virtual screening and in vitro experimental validation was used to identify novel HDAC inhibitors from a chemical database. RESULTS: A virtual screening workflow for HDAC inhibitors were created by integrating ligand- and receptor- based virtual screening methods. Using the virtual screening workflow, 22 hit compounds were selected and further tested via in vitro assays. Enzyme inhibition assays showed that three of the 22 compounds had HDAC inhibitory properties. Among these three compounds, ZINC12555961 significantly inhibited HDAC activity. Further in vitro experiments indicated that ZINC12555961 can selectively inhibit proliferation and promote apoptosis of cancer cells. CONCLUSIONS: In summary, our study presents three new and potent HDAC inhibitors and one of these HDAC inhibitors shows anti-proliferative and apoptosis-inducing activity against various cancer cell lines. These results suggest that the developed virtual screening workflow can provide a useful source of information for the screening and validation of new HDAC inhibitors. The new-found HDAC inhibitors are worthy to further and more comprehensive investigations.

Antiosteoporotic Effects of Huangqi Sanxian Decoction in Cultured Rat Osteoblasts by Proteomic Characterization of the Target and Mechanism.

Huangqi Sanxian decoction (HQSXD) is routinely used for the treatment of osteoporosis in the Chinese traditional healthcare system. However, the targets and mechanism underlying the effect of HQSXD on osteoporosis have not been documented. In the present study, seropharmacology and proteomic approaches (two-dimensional gel electrophoresis combined with mass spectrometry) were used to investigate the effects and possible target proteins of HQSXD on osteoblast. We found that HQSXD-treated rat serum significantly enhanced osteoblast proliferation, differentiation, and mineralization. In HQSXD-S-treated osteoblasts, there were increases in the expression of N-formyl peptide receptor 2 and heparan sulfate (glucosamine) 3-O-sulfotransferase 3A1 and reduction in the expression of alpha-spectrin, prohibitin, and transcription elongation factor B (SIII), polypeptide 1. The identified proteins are associated with cell proliferation, differentiation, signal transcription, and cell growth. These findings might provide valuable insights into the mechanism of antiosteoporotic effect affected by HQSXD treatment in osteoblasts.

[Study on chemical constituents of Inula cappa].

Column chromatographies over silica gel, Sephadex LH-20, reverse phase C18, and MCI, and semi-preparative HPLC were used for separation and purification of constituents from Inula cappa. The 22 compounds were obtained and their strutures were determined by NMR and MS spectra data as nine flavonoids: luteolin (1), apigenin (2), chrysoeriol (3), artemetin (4), 2', 5-di- hydroxy-3, 6, 7, 4', 5'-pentamethoxyflavone (5), chrysosplenol C (6), apigenin-5-0-ß-D-glucopyranoside (7), luteolin-3-methyl, luteolin-3-methylether-4'-0-ß-D-glucopyranoside (8), luteolin-4'-0-ß-D-glucopyranoside (9); four triterpenes: darma-20, 24-dien- 3ß-0-acetate (10), darma-20, 24-dien-3ß-ol (11), epirfiedelanol (12), friedelin (13); three coumarins: scopoletin (14) , isosco- poletin (15) , scopolin(16) , and other types of compounds stigmasta-5, 22-dien-3ß-0-7-one (17), stigmasterol (18), palmitic acid (19), linoleic acid (20), linoleic acid methyl ester (21), (E) -9, 12, 13-trihydroxyoetadee-10-enoie acid (22). Compound 5 is a new natural product. Compounds 3-9, 15, 17, 21, and 22 were isolated from this genus for the first time.

Modelling coupled oscillations in the Notch, Wnt, and FGF signaling pathways during somitogenesis: a comprehensive mathematical model.

Somite formation in the early stage of vertebrate embryonic development is controlled by a complicated gene network named segmentation clock, which is defined by the periodic expression of genes related to the Notch, Wnt, and the fibroblast growth factor (FGF) pathways. Although in recent years some findings about crosstalk among the Notch, Wnt, and FGF pathways in somitogenesis have been reported, the investigation of their crosstalk mechanisms from a systematic point of view is still lacking. In this study, a more comprehensive mathematical model was proposed to simulate the dynamics of the Notch, Wnt, and FGF pathways in the segmentation clock. Simulations and bifurcation analyses of this model suggested that the concentration gradients of both Wnt, and FGF signals along the presomitic mesoderm (PSM) are corresponding to the whole process from start to stop of the segmentation clock. A number of highly sensitive parameters to the segmentation clock's oscillatory pattern were identified. By further bifurcation analyses for these sensitive parameters, and several complementary mechanisms in respect of the maintenance of the stable oscillation of the segmentation clock were revealed.

[Chemical Constituents of Eucommia ulmoides in Guizhou Province].

OBJECTIVE: To study the chemical constituents of Eucommia ulmoides in Guizhou Province. METHODS: Silica gel, Sephadex LH-20, RP-18, MCI and semi-preparative HPLC were used to study the chemical constituents of Eucommia ulmoides, and the chemical structures were elucidated by application of spectral data. RESULTS: 16 compounds were isolated from the bark of Eucommia ulmoides. Their structures were identified as ß-sitosterol (1), cycloeucalenol (2), betulinic acid (3), 24-methylenecycloartenone (4), cycloeucalenone (5), salicifoliol (6), pinoresinol (7), genipin (8) , alternariol (9), balanophonin (10), eucommidiol (11), pinoresinol-4'-O-ß-D-glucopyranoside (12), eucommiol (13), deoxyeucommiol (14), 8-hydroxypinoresinol (15), and dehydrodiconiferyl alcohol -γ'-O-ß-D-glucopyranoside (16). CONCLUSION: Seven compounds, including compounds 2,4 - 6,9, 10 and 15 are isolated from Eucommia ulmoides for the first time, and compound 14 is isolated from the bark of Eucommia ulmoides for the first time.

Systematic analysis of time-series gene expression data on tumor cell-selective apoptotic responses to HDAC inhibitors.

SAHA (suberoylanilide hydroxamic acid or vorinostat) is the first nonselective histone deacetylase (HDAC) inhibitor approved by the US Food and Drug Administration (FDA). SAHA affects histone acetylation in chromatin and a variety of nonhistone substrates, thus influencing many cellular processes. In particularly, SAHA induces selective apoptosis of tumor cells, although the mechanism is not well understood. A series of microarray experiments was recently conducted to investigate tumor cell-selective proapoptotic transcriptional responses induced by SAHA. Based on that gene expression time series, we propose a novel framework for detailed analysis of the mechanism of tumor cell apoptosis selectively induced by SAHA. Our analyses indicated that SAHA selectively disrupted the DNA damage response, cell cycle, p53 expression, and mitochondrial integrity of tumor samples to induce selective tumor cell apoptosis. Our results suggest a possible regulation network. Our research extends the existing research.

Stromal fibroblast activation and their potential association with uterine fibroids (Review).

Uterine fibroids are the most common type of benign, gynecologic neoplasm and are the primary indication for performance of a hysterectomy, accounting for >200,000 hysterectomies annually in the USA. At present, females are younger and exhibit larger leiomyomas at the time of diagnosis. Cancer-associated fibroblasts in tumor microenvironments have emerged as an important target for cancer therapy. Repeated stimulation by infectious or non-infectious agents in the uterine tissues, including inflammation, mechanical forces or hypoxia, stimulate the resident fibroblasts to undergo specific activation and, thus, are significant in tumorigenesis. Furthermore, complex signaling pathways regulate the mechanisms of fibroblastic activation. The current review focuses on the molecular mechanisms of fibroblastic activation and the potential association with uterine leiomyoma pathogenesis, enabling an integrated pathogenic analysis for review of the therapeutic options.

The catalytic triad of testes-specific protease 50 (TSP50) is essential for its function in cell proliferation.

Testes-specific protease 50 (TSP50) is a novelly identified pro-oncogene and it shares a similar enzymatic structure with many serine proteases. Our previous results suggested that TSP50 could promote tumorigenesis through degradation of IκBα protein and activating NF-κB signaling, and the threonine mutation in its catalytic triad could depress TSP50-mediated cell proliferation. However, whether the two other residues in the catalytic triad of TSP50 play a role in maintaining protease activity and tumorigenesis, and the mechanisms involved in this process remain unclear. Here, we constructed and characterized three catalytic triad mutants of TSP50 and found that all the mutants could significantly depress TSP50-induced cell proliferation and colony formation in vitro and tumor formation in vivo, and the aspartic acid at position 206 in the catalytic triad played a more crucial role than threonine and histidine in this process. Mechanistic studies revealed that the mutants in the catalytic triad abolished the enzyme activity of TSP50, but did not change the cellular localization. Furthermore, our data indicated that all the three mutants suppressed activation of NF-κB signal by preventing the interaction between TSP50 and the NF-κB:IκBα complex. Most importantly, we demonstrated that TSP50 could interact with IκBα protein and cleave it directly as a new protease in vitro.

Parthenolide-induced apoptosis, autophagy and suppression of proliferation in HepG2 cells.

PURPOSE: To investigate the anticancer effects and underlying mechanisms of parthenolide on HepG2 human hepatocellular carcinoma cells. MATERIALS AND METHODS: Cell viability was assessed by MTT assay and cell apoptosis through DAPI, TUNEL staining and Western blotting. Monodansylcadaverin(MDC) and AO staining were used to detect cell autophagy. Cell proliferation was assessed by Ki67 immunofluorescence staining. RESULTS: Parthenolide induced growth inhibition in HepG2 cells. DAPI and TUNEL staining showed that parthenolide could increase the number of apoptotic nuclei, while reducing the expression of the anti-apoptotic protein Bcl-2 and elevating the expression of related proteins, like p53, Bax, cleaved caspase9 and cleaved caspase3. Parthenolide could induce autophagy in HepG2 cells and inhibited the expression of proliferation-related gene, Ki-67. CONCLUSIONS: Parthenolide can exert anti-cancer effects by inducing cell apoptosis, activating autophagy and inhibiting cell proliferation.

[Detection of chlorophyll content in water body based on two-dimensional correlation spectroscopy].

Twenty five samples were collected from 10 different ponds in Jiangsu Province of China. According to the different water status and surface area of each pond, different numbers of water samples were collected. The present paper aims to detect chlorophyll content in water body based on hyperspectrum. The visible and near infrared spectral transmittance of the water samples was measured by using a Shimadzu UV-2450 spectrograph. At the same time, the chlorophyll content of each sample was measured using hot-ethanol extraction method in the laboratory. Then the spectral characteristics were analyzed for the water samples and the results showed that with chlorophyll concentration increasing, spectral transmittance decreased gradually. There is an apparent transmission valley at 676 nm. And then two dimensional correlation spectrum technology was used to analyze the sensitive absorption band of chlorophyll in water body. Comprehensive observation of the spectral characteristics of water samples can be carried out much accurately by analyzing two-dimensional correlation spectra of synchronous and asynchronous spectrograms. And the effective spectral response bands of the chlorophyll content were found at 488 and 676 nm. Then the NDWCI (normalized difference water chlorophyll index) was established with the transmittance of red band and blue band. Two regression models were built to predict the chlorophyll concentration in water. One is a multiple linear regression model based on the original transmittances at 488 and 676 nm. The other is the linear regression model based on NDWCI. By comparison, the model based on NDWCI was better. The R2 of its training model reached to 0.7712, and the root mean square error of calibration was 45.5099 mg x L(-1). The R2 of prediction model reached to 0.7658, and the root mean square error of prediction was 39.5038 mg x L(-1). It reached to a practical level to predict the chlorophyll content in water body rapidly.

Alantolactone induces cell apoptosis partially through down-regulation of testes-specific protease 50 expression.

Testes-specific protease 50 (TSP50) is aberrantly expressed in many cancer biopsies and plays a crucial role in tumorigenesis, which make it a potential cancer therapeutic target for drug discovery. Here, we constructed a firefly luciferase reporter driven by the TSP50 gene promoter to screen natural compounds capable of inhibiting the expression of TSP50. Then we identified alantolactone, a sesquiterpene lactone, could efficiently inhibit the promoter activity of TSP50 gene, further results revealed that alantolactone also efficiently inhibited the expression of TSP50 in both mRNA and protein levels. Moreover, we found alantolactone could increase the ratio of Bax/Bcl-2, and activate caspase-9 and caspase-3 in the cancer cells with high expression of TSP50, surprisingly, the same effects can also be observed in the same cells just by knockdown of TSP50 gene expression. Furthermore, our results suggested that overexpression of TSP50 decreased the cell sensitivity to alantolactone-induced apoptosis in those cancer cells. Taken together, these results suggest that alantolactone induces mitochondrial-dependent apoptosis at least partially via down-regulation of TSP50 expression.

Alantolactone induces apoptosis in RKO cells through the generation of reactive oxygen species and the mitochondrial pathway.

Alantolactone, a methanol extract of Inula helenium, possesses anticancer properties in a number of cancer cell lines. However, its anticancer effect on human colorectal cancer cells and the underlying mechanisms remain to be elucidated. In the present study, the effects of alantolactone on cell viability and apoptosis in RKO human colon cancer cells were investigated. Alantolactone treatment of RKO cells was found to result in dose­dependent inhibition of cell viability and induction of apoptosis, accompanied with the accumulation of reactive oxygen species (ROS) and the disruption of mitochondrial membrane potential. In addition, these effects were blocked with N­acetylcysteine, a specific ROS inhibitor. Western blotting indicated that exposure of RKO cells to alantolactone is associated with the downregulation of Bcl­2, induction of Bax and activation of caspase­3 and ­9. These results indicated that a ROS­mediated mitochondria­dependent pathway is involved in alantolactone­induced apoptosis. From these observations, it was hypothesized that alantolactone may be used for the treatment of human colon cancer.

[Effect of soil moisture on prediction of soil total nitrogen using NIR spectroscopy].

As one of the most important components of soil liutrient, it is necessary to obtain the soil total nitrogen(STN)content in precision agriculture. It is a feasible method to predict soil total nitrogen content based on NIRS. However, the effect of soil moisture content (SMC) on the prediction of STN is very serious. In the present research, the effect of SMC was discussed from qualitative analysis and quantitative analysis by the Fourier spectrum analyzer MATRIX_I. Firstly, sixty soil samples with different STN and SMC were scanned by the MATRIX_I. It was found that the reflectince of soil samples in near infrared region decreased with the increase in SMC. Subsequently, Moisture absorbance index (MAI) was proposed by the diffuse of absorbance at the wavelengths of 1 450 and 1 940 nm to classify soil properties and then correction factor was present Finally, the STN forecasting model with BP NN method was established by the revised absorbance data at the six wavelengths of 940, 1 050, 1,100, 1,200, 1,300 and 1,550 nm. The model was evaluated by correlation coefficient of Rc, correlation coefficient of Rv, root mean square error of calibration (RMSEC), root mean square error of validation (RMSEP) and residual prediction deviation (RPD). Compared with the model obtained from original spectral data, both the accuracy and the stability were improved. The new model was with Rc of 0.86, Rv of 0.81, RMSEC of 0.06, RMSEP of 0.05, and RPD of 2.75. With the first derivative of the revised absorbance, the RPD became 2.90. The experiments indicated that the method could eliminate the effect of SMC on the prediction of STN efficiently.

Mathematical models for the Notch and Wnt signaling pathways and the crosstalk between them during somitogenesis.

BACKGROUND: Somitogenesis is a fundamental characteristic feature of development in various animal embryos. Molecular evidence has proved that the Notch and Wnt pathways play important roles in regulating the process of somitogenesis and there is crosstalk between these two pathways. However, it is difficult to investigate the detailed mechanism of these two pathways and their interactions in somitogenesis through biological experiments. In recent years some mathematical models have been proposed for the purpose of studying the dynamics of the Notch and Wnt pathways in somitogenesis. Unfortunately, only a few of these models have explored the interactions between them. RESULTS: In this study, we have proposed three mathematical models for the Notch signalling pathway alone, the Wnt signalling pathway alone, and the interactions between them. These models can simulate the dynamics of the Notch and Wnt pathways in somitogenesis, and are capable of reproducing the observations derived from wet experiments. They were used to investigate the molecular mechanisms of the Notch and Wnt pathways and their crosstalk in somitogenesis through the model simulations. CONCLUSIONS: Three mathematical models are proposed for the Notch and Wnt pathways and their interaction during somitogenesis. The simulations demonstrate that the extracellular Notch and Wnt signals are essential for the oscillating expressions of both Notch and Wnt target genes. Moreover, the internal negative feedback loops and the three levels of crosstalk between these pathways play important but distinct roles in maintaining the system oscillation. In addition, the results of the parameter sensitivity analysis of the models indicate that the Notch pathway is more sensitive to perturbation in somitogenesis.