Posttraumatic glaucoma in southern China: A ten-year retrospective study.

PURPOSE: To analyze posttraumatic glaucoma regarding its demographics, presentations, different causes, surgical modalities, and hospitalization burden among patients in southern China. METHODS: This retrospective study investigated all individuals with posttraumatic glaucoma admitted to the Zhongshan Ophthalmic Center of Sun Yat-Sen University from January 2012 through December 2021. RESULTS: Out of 2211 cases, 64.82% had closed globe injury (CGI), 28.22% had open globe injury (OGI), and 6.96% had chemical injury (CI). The mean age of all patients was 44.45 ± 19.45 years old. Males (83.36%), rural patients (56.17%), and farmers (27.14%) predominantly had posttraumatic glaucoma. The most common external injury mechanism was blunt objects (37.82%). Compared with the other two groups, the majority of surgical modalities were cataract extraction (27.12%) in the CGI group, combined anterior-posterior surgery (34.79%) in the OGI group, and cyclocryotherapy/cyclophotoagulation (49.1%) in the CI group. The CI group had higher times of hospitalization (3.542 ± 0.242) and hospitalization duration (8.373 ± 0.743 days), whereas the OGI group had more operation expense ($ 1476.729 ± 11.047) and medical consumables expense per head ($ 962.578 ± 25.801). CONCLUSION: Blunt injury, males, adults, farmers, and rural patients were high-risk factors for posttraumatic glaucoma. Chemical-induced glaucoma management requires a longer hospitalization period, while OGI requires more medical expenditure. This knowledge provides a new reference for clinicians to accurately diagnose and intervene in posttraumatic glaucoma. It also suggests that more education and long-term surveillance are needed regarding the presence of glaucoma after ocular trauma.

The profile of gut microbiota and central carbon-related metabolites in primary angle-closure glaucoma patients.

PURPOSE: To explore the profile of gut microbiota and central carbon-related metabolites in patients with primary angle-closure glaucoma (PACG). METHODS: The fecal microbiotas of 30 PACG patients and 30 healthy participants were detected via 16S rRNA sequencing. Targeted liquid chromatography-mass spectrometry was used to examine serum central carbon-related metabolites. The correlations among metabolites, microbiotas and clinical presentations were also explored. RESULTS: Although the α and ß diversity between the PACG and control groups did not show a significant difference, the distribution of Blautia and Fusicatenibacter decreased significantly in the PACG group. Functional annotations of microbiota enrichment showed that the most dominant pathway was related to host metabolism. In the PACG patients, seven central carbon metabolites, namely adenosine 5'-diphosphate, dGDP, phosphoenolpyruvic acid, d-ribulose 5-phosphate, d-xylulose 5-phosphate, glucuronic acid, and malonic acid, decreased significantly, whereas two metabolites, citric acid and isocitrate, increased obviously. The mean RNFL thickness was positively correlated with phosphoenolpyruvic acid, the VF-MD was positively correlated with glucuronic acid, and the abundance of Blautia was negatively associated with citric acid. CONCLUSION: Few species of gut microbiota were altered in the PACG patients compared to the healthy subjects. A distinct difference in the phenotype of the central carbon-related metabolites of PACG and their correlation with clinical presentations and microbiota suggests potential mechanisms of RGC impairment and novel intervention targets.

Ultrasound Biomicroscopy Might Predict the Outcome of Phacoemulsification-Visco Dissection in Medically Controlled Primary Angle-Closure Glaucoma Eye With Extensive Peripheral Anterior Synechia.

Objective: The treatment procedures of primary angle-closure glaucoma (PACG) with extensive peripheral anterior synechia (PAS) is a subject of debate. This study is to investigate the clinical features of phacoemulsification (Phaco)-visco dissection in medically controlled PACG patients with PAS > 180° and evaluate the predictability of Ultrasound Biomicroscopy (UBM) parameters on postoperative intraocular pressure (IOP). Methods: 48 eyes (48 patients) with acute angle-closure glaucoma (AACG) and 30 eyes (30 patients) with chronic angle-closure glaucoma (CACG) were prospectively included. All patients underwent phaco-viscogoniolysis and foldable lens implantation and were followed for 1 year after surgery. We analyzed preoperative and postoperative IOP, the numbers of anti-glaucoma medicine, the visual field value, the extent of PAS, and UBM parameters alterations, and evaluated the correlation between preoperative UBM parameters and one-year postoperative IOP. Results: IOP reduced significantly from 16.24 ± 4.33 to 14.49 ± 3.69 mmHg in AACG group and from 16.16 ± 3.69 mmHg to 14.31 ± 4.12 mmHg in CACG group, and PAS decreased significantly from 270 ± 60.33 to 171 ± 56.44° in AACG group and from 285 ± 70.46 to 168 ± 61.32° in CACG group, and the number of anti-glaucoma drugs decreased significantly in both groups. Several UBM parameters, including anterior chamber depth, trabecular iris angle, and peripheral iris thickness 500 increased while iris convex reduced considerably in the two groups, and angle opening distance 500 and trabecular-meshwork ciliary process angle increased significantly only in AACG group. One-year postoperative IOP correlated with preoperative angle opening distance 500 and trabecular iris angle negatively and iris convex positively. Conclusion: Phaco-visco dissection can effectively reduce IOP, the numbers of glaucomatous medications, and PAS in medically controlled PACG patients with extensive PAS. UBM parameters might be valuable for analyzing postoperative anterior segment structure and predicting postoperative IOP of Phaco-visco dissection in PACG patients with extensive PAS.

The Profile of Secondary Glaucoma in China: A Study of Over 10,000 Patients.

BACKGROUND: Few studies have investigated the epidemiology of secondary glaucoma (SG) in China. This study analyzed the current profile of admitted patients with SG at the largest ophthalmic center in China. METHODS: SG cases were retrieved retrospectively by International Classification of Disease-10 clinical coding data from January 2010 to December 2019. Demographic data, etiologies, and the management of SG were analyzed. The ratios of the etiologies were compared with previously reported data from other regions. The etiologies and management between the 2010 to 2014 group and the 2015 to 2019 group were compared. RESULTS: A total of 11,730 cases were enrolled. The mean age of the patients with SG was 44.45±19.45 years old. Men (66.94%) were more vulnerable than women (33.06%). The etiologies of SG in 2010 to 2019 were trauma (28%), vascular disease (18%), lens-induced (9%), inflammation (11%), drug-induced (2%), anterior segment surgery (7%), posterior segment surgery (11%), syndrome-associated (4%), and tumors (1%). Compared with other regions, our data have a higher proportion of trauma and vascular disease-associated SG. Compared with 2010 to 2014, trauma-induced SG declined, and drug-induced SG, anterior segment surgery, and syndrome-associated SG increased in 2015 to 2019 (P<0.001). Vascular disease-associated SG cases were older than trauma-induced SCs and had a higher percentage in retired patients (P<0.001), whereas trauma-induced SGs were more prevalent in pediatric patients than vascular disease-related SGs (P<0.001). In addition, the application of drainage device implantation, cataract surgery, and cyclophotocoagulation increased, whereas trabeculectomy and anterior chamber paracentesis and cyclocryotherapy decreased in 2015 to 2019 (P<0.005). CONCLUSION: Although the etiology spectrum has changed during the last 10 years, trauma and vascular disease are still common causes of SG in southern China. Traditional antiglaucoma surgery decreased gradually, and more advanced treatments emerged for its treatment. Up-to-date knowledge of SGs reflects the impact of economic development and ophthalmic service improvement on SGs and is of great value for ophthalmologists to detect SGs early and manage them in a timely manner.

Genome-wide identification, structure characterization, and expression pattern profiling of aquaporin gene family in cucumber.

BACKGROUND: Aquaporin (AQP) proteins comprise a group of membrane intrinsic proteins (MIPs) that are responsible for transporting water and other small molecules, which is crucial for plant survival under stress conditions including salt stress. Despite the vital role of AQPs, little is known about them in cucumber (Cucumis sativus L.). RESULTS: In this study, we identified 39 aquaporin-encoding genes in cucumber that were separated by phylogenetic analysis into five sub-families (PIP, TIP, NIP, SIP, and XIP). Their substrate specificity was then assessed based on key amino acid residues such as the aromatic/Arginine (ar/R) selectivity filter, Froger's positions, and specificity-determining positions. The putative cis-regulatory motifs available in the promoter region of each AQP gene were analyzed and results revealed that their promoter regions contain many abiotic related cis-regulatory elements. Furthermore, analysis of previously released RNA-seq data revealed tissue- and treatment-specific expression patterns of cucumber AQP genes (CsAQPs). Three aquaporins (CsTIP1;1, CsPIP2;4, and CsPIP1;2) were the most transcript abundance genes, with CsTIP1;1 showing the highest expression levels among all aquaporins. Subcellular localization analysis in Nicotiana benthamiana epidermal cells revealed the diverse and broad array of sub-cellular localizations of CsAQPs. We then performed RNA-seq to identify the expression pattern of CsAQPs under salt stress and found a general decreased expression level of root CsAQPs. Moreover, qRT-PCR revealed rapid changes in the expression levels of CsAQPs in response to diverse abiotic stresses including salt, polyethylene glycol (PEG)-6000, heat, and chilling stresses. Additionally, transient expression of AQPs in N. benthamiana increased leaf water loss rate, suggesting their potential roles in the regulation of plant water status under stress conditions. CONCLUSIONS: Our results indicated that CsAQPs play important roles in response to salt stress. The genome-wide identification and primary function characterization of cucumber aquaporins provides insight to elucidate the complexity of the AQP gene family and their biological functions in cucumber.

Evaluation of early changes of macular function and morphology by multifocal electroretinograms in patients with nasopharyngeal carcinoma after radiotherapy.

OBJECTIVE: To assess the role of multifocal electroretinograms (mfERGs) and optical coherence tomography (OCT) for detecting early changes in macular functions of patients with nasopharyngeal carcinoma (NPC) after radiotherapy. METHODS: mfERGs and OCT were used to examine a NPC group (36 NPC patients after radiotherapy without clinically visible radiation retinopathy, 36 eyes) and a normal control group (25 healthy individuals, 25 eyes) with the same procedure and parameters. The two groups of mfERG were summarized by calculating ring averages, response density, N1 amplitude and P1 and N1 latencies were analysed. OCT scan thickness was summarized into ETDRS regions for comparison. RESULTS: Compared with controls, the NPC group had significantly decreased P1 response densities in 1-4 ring regions and N1 amplitudes in 1-3 rings (P < 0.01). P1 latencies were obviously prolonged in rings 1 (P < 0.01). In four quadrants (inferonasal, superonasal, inferotemporal and superotemporal) of the mfERG response waveforms, the NPC group had significantly decreased P1 response densities and N1 amplitudes mainly in the inferonasal and inferotemporal quadrants, showing statistically significant differences from the control group (P < 0.0125). But for the OCT results, there is no statistically significant difference between the NPC group and the control group. CONCLUSIONS: In NPC patients after radiotherapy, there may be changes in the mfERGs before any visible fundus lesions appeared as radiation macular oedema. Since the global OCT macular thickness analysis cannot reveal early changes, the mfERGs can objectively and quantitatively assess the earlier changes in macular function in NPC patients.

Silicon enhances the salt tolerance of cucumber through increasing polyamine accumulation and decreasing oxidative damage.

Silicon can increase salt tolerance, but the underlying mechanism has remained unclear. Here, we investigated the effect of silicon on polyamine metabolism and the role of polyamine accumulation in silicon-mediated salt tolerance in cucumber. Seedlings of cucumber 'JinYou 1' were subjected to salt stress (75 mM NaCl) in the presence or absence of added 0.3 mM silicon. Plant growth, polyamine metabolism and effects of exogenous polyamines and polyamine synthesis inhibitor dicyclohexylammonium sulphate on oxidative damage were investigated. The results showed that salt stress inhibited plant growth and decreased leaf chlorophyll levels and the maximum quantum yield of PSII, and added silicon ameliorated these negative effects. Salt stress increased polyamine accumulation in the leaves and roots. Compared with salt stress alone, overall, silicon addition decreased free putrescine concentrations, but increased spermidine and spermine concentrations in both leaves and roots under salt stress. Silicon application resulted in increased polyamine levels under salt stress by promoting the activities of S-adenosylmethionine decarboxylase and arginine decarboxylase while inhibiting the activity of diamine oxidase. Exogenous application of spermidine and spermine alleviated salt-stress-induced oxidative damage, whereas polyamine synthesis inhibitor eliminated the silicon-mediated decrease in oxidative damage. The results suggest that silicon-enhanced polyamine accumulation in cucumber under salt stress may play a role in decreasing oxidative damage and therefore increase the salt tolerance.

High glucose-induced epithelial-mesenchymal transition contributes to the upregulation of fibrogenic factors in retinal pigment epithelial cells.

It has been reported that epithelial-mesenchymal transition (EMT) mediates multiple physiological and pathological processes. However, the occurrence and the pathogenic role of high glucose-induced EMT in retinal pigment epithelial cells (RPE cells) is unknown. The aim of this study was to examine the effects of high glucose on EMT in RPE cells. Cultured RPE cells were exposed to 25 mM D-glucose. A vector encoding the Snail gene and siRNA targeting Snail (Snail siRNA) were transfected into the cells to induce the overexpression or silencing of Snail, respectively. AKT and extracellular signal-regulated kinase (ERK) inhibitors were used to block the activation of AKT and ERK, respectively. The levels of EMT markers, fibrogenic factors, phosphorylated ERK and phosphorylated AKT were determined by western blot analysis and immunofluorescence staining. Cell migration was evaluated by wound healing assay. Our results revealed that high glucose elevated the expression of the key EMT transcriptional factor, Snail, and that of other mesenchymal makers, and promoted cell migration. Moreover, the overexpression of Snail elevated the levels of fibronectin and connective tissue growth factor (CTGF), whereas the silencing of Snail decreased the expression of fibronectin and CTGF induced by high glucose in the cells. Mechanistically, the AKT inhibitor (AKT inhibitor IV) and ERK inhibitor (U0126) significantly decreased the expression of Snail, as well as the levels of fibronectin and CTGF which were induced by high glucose. On the whole, and to the best of our knowedge, the present study is the first to demonstrate the upregulation of mesenchymal markers in RPE cells induced by high glucose, and suggest that mesenchymal transition may be involved in the pathological processes of retinal diseases.

Recurrent corneal melting in the paraneoplastic pemphigus associated with Castleman's disease.

BACKGROUND: The ocular presentation of Castleman's disease (CD)-associated paraneoplastic pemphigus (PNP) has rarely been reported. In this report, we describe a young patient with CD-associated PNP who had recurrent corneal ulceration in addition to cicatrizing conjunctivitis. CASE PRESENTATION: We describe a case of 23-year-old male with mucocutaneous erosion and conjunctival injection and erosion who was found to have PNP. Pelvic hyaline-vascular CD was detected and completely excised. The mucocutaneous lesions improved postoperatively. Two years after pelvic surgery, the patient gradually developed conjunctival symblepharon in both eyes and pterygium in the right eye. The patient then underwent a successful exclusion of the symblepharon, an excision of the pterygium and an amniotic membrane transplantation in the right eye. However, after 6 months, he experienced an aseptic corneal ulcer and recurrent pterygiumin the right eye. After treatment with systemic and local immunosuppressive medications, the corneal ulcer gradually healed and remained stable. CONCLUSION: Corneal ulceration and melting, in addition to conjunctivitis, as a complication of CD-associated PNP, can be successfully managed with systemic and local immunosuppressants.

Distinct physiological responses of tomato and cucumber plants in silicon-mediated alleviation of cadmium stress.

The alleviative effects of silicon (Si) on cadmium (Cd) toxicity were investigated in cucumber (Cucumis sativus L.) and tomato (Solanum lycopersicum L.) grown hydroponically. The growth of both plant species was inhibited by 100 µM Cd, but Si application counteracted the adverse effects on growth. Si application significantly decreased the Cd concentrations in shoots of both species and roots of cucumber. The root-to-shoot transport of Cd was depressed by added Si in tomato whereas it was increased by added Si in cucumber. The total content of organic acids was decreased in tomato leaves but increased in cucumber roots and leaves by Si application under Cd stress. Si application also increased the cell wall polysaccharide levels in the roots of both species under Cd toxicity. Si-mediated changes in levels of organic acids and cell wall polysaccharides might contribute to the differences in Cd transport in the two species. In addition, Si application also mitigated Cd-induced oxidative damage in both species. The results indicate that there were different mechanisms for Si-mediated decrease in shoot Cd accumulation: in tomato, Si supply decreased root-to-shoot Cd transport; whereas in cucumber, Si supply reduced the Cd uptake by roots. It is suggested that Si-mediated Cd tolerance is associated with different physiological responses in tomato and cucumber plants.

A novel procedure for statistical inference and verification of gene regulatory subnetwork.

BACKGROUND: The reconstruction of gene regulatory network from time course microarray data can help us comprehensively understand the biological system and discover the pathogenesis of cancer and other diseases. But how to correctly and efficiently decifer the gene regulatory network from high-throughput gene expression data is a big challenge due to the relatively small amount of observations and curse of dimensionality. Computational biologists have developed many statistical inference and machine learning algorithms to analyze the microarray data. In the previous studies, the correctness of an inferred regulatory network is manually checked through comparing with public database or an existing model. RESULTS: In this work, we present a novel procedure to automatically infer and verify gene regulatory networks from time series expression data. The dynamic Bayesian network, a statistical inference algorithm, is at first implemented to infer an optimal network from time series microarray data of S. cerevisiae, then, a weighted symbolic model checker is applied to automatically verify or falsify the inferred network through checking some desired temporal logic formulas abstracted from experiments or public database. CONCLUSIONS: Our studies show that the marriage of statistical inference algorithm with model checking technique provides a more efficient way to automatically infer and verify the gene regulatory network from time series expression data than previous studies.

Computational analysis of the roles of ER-Golgi network in the cell cycle.

BACKGROUND: ER-Golgi network plays an important role in the processing, sorting and transport of proteins, and it's also a site for many signaling pathways that regulate the cell cycle. Accumulating evidence suggests that, the stressed ER and malfunction of Golgi apparatus are associated with the pathogenesis of cancer and Alzheimer's disease (AD). Our previous work discovered and verified that altering the expression levels of target SNARE and GEF could modulate the size of Golgi apparatus. Moreover, Golgi's structure and size undergo dramatic changes during the development of several diseases. It is of importance to investigate the roles of ER-Golgi network in the cell cycle progression and some diseases. RESULTS: In this work, we first develop a computational model to study the ER stress-induced and Golgi-related apoptosis-survival signaling pathways. Then, we propose and apply both asynchronous and synchronous model checking methods, which extend our previous verification technique, to automatically and formally analyze the ER-Golgi-regulated signaling pathways in the cell cycle progression through verifying some computation tree temporal logic formulas. CONCLUSIONS: The proposed asynchronous and synchronous verification technique has advantages for large network analysis and verification over traditional simulation methods. Using the model checking method, we verified several Alzheimer's disease and cancer-related properties, and also identified important proteins (NFκB, ATF4, ASK1 and TRAF2) in the ER-Golgi network, which might be responsible for the pathogenesis of cancer and AD. Our studies indicate that targeting the ER stress-induced and Golgi-related pathways might serve as potent therapeutic targets for the treatment of cancer and Alzheimer's disease.

Pathway-gene identification for pancreatic cancer survival via doubly regularized Cox regression.

BACKGROUND: Recent global genomic analyses identified 69 gene sets and 12 core signaling pathways genetically altered in pancreatic cancer, which is a highly malignant disease. A comprehensive understanding of the genetic signatures and signaling pathways that are directly correlated to pancreatic cancer survival will help cancer researchers to develop effective multi-gene targeted, personalized therapies for the pancreatic cancer patients at different stages. A previous work that applied a LASSO penalized regression method, which only considered individual genetic effects, identified 12 genes associated with pancreatic cancer survival. RESULTS: In this work, we integrate pathway information into pancreatic cancer survival analysis. We introduce and apply a doubly regularized Cox regression model to identify both genes and signaling pathways related to pancreatic cancer survival. CONCLUSIONS: Four signaling pathways, including Ion transport, immune phagocytosis, TGFß (spermatogenesis), regulation of DNA-dependent transcription pathways, and 15 genes within the four pathways are identified and verified to be directly correlated to pancreatic cancer survival. Our findings can help cancer researchers design new strategies for the early detection and diagnosis of pancreatic cancer.

Over-expression of SlCycA3 gene in Arabidopsis accelerated the cell cycle transition.

We characterised an A-type cyclin SlCycA3 (AJ243453) from tomato (Solanum lycopersicum L.). Phylogenetic analysis based on the deduced amino acid sequence revealed that SlCycA3 was 71% identical to A3-type cyclin in Nicotiana tabacum L. (CAA63540), 48% identical to its homologue found in Arabidopsis thaliana (NP_199122), and 48% identical to its homologue in Pisum sativum L. (CAB77269). SlCycA3 gene was transformed into Arabidopsis plants in order to study its function. The hypocotyl length of transgenic plants was approximately half the length of wild-type plants, and the cell size in the transgenic lines was also smaller. The transgenic plants had longer roots than the wild type. Overexpression of SlCycA3 gene accelerated the cell cycle from G1/S transition to early M-phase, thereby accelerating the cell division. When the plants were treated with IAA and 3-indolebutyric acid (IBA) for 2 days, the transgenic plants produced more lateral roots than wild type. Treatment with IBA significantly increased the cell number in the G2-phase in transgenic plants compared with wild type after treatment for 10 days, whereas the proportion of cells in the S-phase was strongly increased by IAA treatment both in wild-type and transgenic plants. These results suggest a possible key role for cyclin in regulating root growth and development and provide some evidence of cell division underlying hormone treatment in plants.

Analysis of intercellular signal transduction in the tumor microenvironment.

BACKGROUND: Recent cancer studies revealed, the interaction between pancreatic cancer cells and pancreatic stellate cells is of importance in the cancer progression. The activation of stellate cells is mediated by some growth factors and cytokines secreted by the cancer cells. In turn, the activated stellate cells will synthesize and secrete multiple growth factors to continuously stimulate the growth of surrounding cancer cells through paracrine pathways. The mechanism behind the evolution of stellate cells from quiescent state to a cancer-associated phenotype is still not well understood. RESULTS: To systematically investigate the interaction between cancer cells and stellate cells, we constructed a multicellular discrete value model, which is composed of several intracellular and intercellular signaling pathways that are frequently mutated in the pancreatic cancer, to study the cell cycle progression and angiogenesis. We, then, introduced and applied a formal verification technique, Symbolic Model Checking, to automatically analyze the cells' proliferation, angiogenesis and apoptosis in the proposed signal transduction model of tumor microenvironment. CONCLUSIONS: Our studies predicted some important temporal logic properties and dynamic behaviors in the pancreatic cancer cells and stellate cells. The verification technique identified several signaling components, including the RAS, RAGE, AKT, IKK, DVL, RB and PTEN, whose mutation or loss of function can promote cell growth and inhibit apoptosis, some of which have been confirmed by existing experiments. Our formal studies demonstrated that, the bidirectional interaction between cancer cells and stellate cells could significantly increase cell proliferation, inhibit apoptosis, induce tumor angiogenesis, and promote cancer metastasis.

Downregulation of VEGF mRNA expression by triamcinolone acetonide acetate-loaded chitosan derivative nanoparticles in human retinal pigment epithelial cells.

BACKGROUND: The purpose of this study was to investigate the downregulation of mRNA expression of vascular endothelial growth factor (VEGF) by triamcinolone acetonide acetate (TAA)-loaded chitosan nanoparticles in human retinal pigment epithelial cells. METHODS: TAA-loaded deoxycholic acid-modified chitosan (TAA/DA-Chit) nanoparticles were prepared via a self-assembly mechanism, and their morphology and zeta potential were examined by transmission electron microscopy and zeta potential analysis, respectively. DA-Chit and TAA/DA-Chit nanoparticle toxicity was evaluated using a Cell Counting Kit-8 assay. The efficiency of cellular uptake was determined using fluorescein isothiocyanate-labeled DA-Chit nanoparticles, in place of TAA/DA-Chit nanoparticles, assessed by both inverted fluorescence microscopy and flow cytometry. Downregulation of VEGF mRNA expression by TAA/DA-Chit nanoparticles was further investigated by real-time reverse transcription polymerase chain reaction (RT-PCR) assay of the treated human retinal pigment epithelial cells. RESULTS: TAA/DA-Chit nanoparticles were prepared with a TAA-loading capacity in the range of 12%-82%, which increased the water solubility of TAA from 0.3 mg/mL to 2.1 mg/mL. These nanoparticles showed oblate shapes 100-550 nm in size in transmission electron microscopic images and had positive zeta potentials. The Cell Counting Kit-8 assay indicated that the DA-Chit and TAA/DA-Chit nanoparticles had no toxicity and low toxicity, respectively, to human retinal pigment epithelial cells. Fluorescein isothiocyanate-labeled DA-Chit nanoparticle uptake by human retinal pigment epithelial cells was confirmed by inverted fluorescence microscopy and flow cytometry. Real-time RT-PCR assay showed that the VEGF mRNA level decreased after incubation of human retinal pigment epithelial cells with TAA/DA-Chit nanoparticles. CONCLUSION: TAA/DA-Chit nanoparticles had a downregulating effect on VEGF mRNA expression in human retinal pigment epithelial cells and low cytotoxicity, which might be beneficial characteristics for the development of future treatment for diabetic retinopathy.

A transcriptome analysis by lasso penalized Cox regression for pancreatic cancer survival.

Pancreatic cancer is the fourth leading cause of cancer deaths in the United States with five-year survival rates less than 5% due to rare detection in early stages. Identification of genes that are directly correlated to pancreatic cancer survival is crucial for pancreatic cancer diagnostics and treatment. However, no existing GWAS or transcriptome studies are available for addressing this problem. We apply lasso penalized Cox regression to a transcriptome study to identify genes that are directly related to pancreatic cancer survival. This method is capable of handling the right censoring effect of survival times and the ultrahigh dimensionality of genetic data. A cyclic coordinate descent algorithm is employed to rapidly select the most relevant genes and eliminate the irrelevant ones. Twelve genes have been identified and verified to be directly correlated to pancreatic cancer survival time and can be used for the prediction of future patient's survival.

Analysis and verification of the HMGB1 signaling pathway.

BACKGROUND: Recent studies have found that overexpression of the High-mobility group box-1 (HMGB1) protein, in conjunction with its receptors for advanced glycation end products (RAGEs) and toll-like receptors (TLRs), is associated with proliferation of various cancer types, including that of the breast and pancreatic. RESULTS: We have developed a rule-based model of crosstalk between the HMGB1 signaling pathway and other key cancer signaling pathways. The model has been simulated using both ordinary differential equations (ODEs) and discrete stochastic simulation. We have applied an automated verification technique, Statistical Model Checking, to validate interesting temporal properties of our model. CONCLUSIONS: Our simulations show that, if HMGB1 is overexpressed, then the oncoproteins CyclinD/E, which regulate cell proliferation, are overexpressed, while tumor suppressor proteins that regulate cell apoptosis (programmed cell death), such as p53, are repressed. Discrete, stochastic simulations show that p53 and MDM2 oscillations continue even after 10 hours, as observed by experiments. This property is not exhibited by the deterministic ODE simulation, for the chosen parameters. Moreover, the models also predict that mutations of RAS, ARF and P21 in the context of HMGB1 signaling can influence the cancer cell's fate - apoptosis or survival - through the crosstalk of different pathways.

Up-regulation of glutathione metabolism and changes in redox status involved in adaptation of reed (Phragmites communis) ecotypes to drought-prone and saline habitats.

The glutathione (GSH) metabolic characteristics and redox balance in three ecotypes of reed (Phragmites communis), swamp reed (SR), dune reed (DR), and heavy salt meadow reed (HSMR), from different habitats in desert regions of northwest China were investigated. The DR possessed the highest rate of GSH biosynthesis and metabolism with the lowest levels of total and reduced GSH and its biosynthetic precursors, gamma-glutamylcysteine (gamma-EC) and cysteine (Cys), of the three reed ecotypes. This suggests that a higher rate of GSH biosynthesis and metabolism, but not GSH accumulation, might be involved in the adaptation of this terrestrial reed ecotype to its dry habitat. The HSMR shared this profile although it exhibited the highest reduced thiol levels of the three ecotypes. Two key enzymes in the Calvin-cycle possessing exposed sulfhydryl groups, NADP(+)-dependent glyceraldehydes-3-phosphate dehydrogenase (G3PD) and fructose-1,6-bisphosphatase (FBPase), and other two key enzymes in the pentose-phosphate pathway (PPP), glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6-PGD), had very similar activities in the three reed ecotypes. Compared to the SR, the DR and HSMR had higher ratios of NADPH/NADP+ and NADH/NAD+, indicating that a more reduced redox status in the plant cells might be involved in the survival and adaptation of the two terrestrial reed ecotypes to long-term drought and salinity, respectively. These results suggest that changes of GSH metabolism and redox balance were important components of the adaptation of reed, a hydrophilic plant, to more extreme dune and saline habitats. The coordinated up-regulations of the rate of GSH biosynthesis and metabolism and reduction state of redox status of plant cells, conferred on the plant high resistance or tolerance to long-term drought and salinity.