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Biomedical subjects

Dong Yang

Publications and source records attributed to Dong Yang.

At least 19 recordsLinked to original sources

Discovery of Sphaeriaurantins as Rapid-Acting Antiplasmodials with Dual Activity in Blood and Liver Stages.

The rapid emergence of resistance in the malaria-causing protozoan Plasmodium falciparum has heightened the demand for treatments with novel modes of action. Having evolved to produce a myriad of structurally diverse natural products (NPs) as defenses against soil-dwelling parasites including protozoa, Actinomycetota strains are a promising source for the discovery of NPs as antiplasmodial drug leads. Herein, the selective inhibition of P. falciparum is reported for five distinct NP families from Actinomycetota, including an unprecedented family of glycosylated type II polyketides termed sphaeriaurantins (SPAs). The structures of SPAs were established through the combination of MS and NMR spectroscopic data analysis, derivatization and comparison of the deoxyhexose moieties to authentic standards, and quantum chemical calculations, including 1H and 13C NMR chemical shifts and electronic circular dichroism (ECD) spectra. The three isolated SPA congeners reveal that the characteristic pseudodimeric structure of the SPA family of NPs, likely introduced at a late stage of the SPA biosynthesis, is highly relevant for the observed low nanomolar activity. SPA A exhibits a rapid killing profile, with activities across all intraerythrocytic stages, and potent liver stage efficacy, as well as a low propensity for resistance development. Taken together, these results suggest a mode of action that most likely is distinct from the existing antimalarials, supporting SPA A as a promising antimalarial drug lead for further development.

Plasmodium falciparum↗

Effect of the melt granulation technique on the dissolution characteristics of griseofulvin.

This work describes a melt granulation technique to improve the dissolution characteristics of a poorly water-soluble drug, griseofulvin. Melt granulation technique is a process by which pharmaceutical powders are efficiently agglomerated by a meltable binder. The advantage of this technique compared to a conventional granulation is that no water or organic solvents is needed. Because there is no drying step, the process is less time consuming and uses less energy than wet granulation. Granules were prepared in a lab scale high shear mixer, using a jacket temperature of 60 degrees C and an impeller speed of approximately 20,000 rpm. The effect of drug loading (2.5/5%), binder (PEG 3350/Gelucire 44/14), filler (starch/lactose), and HPMC on the dissolution of griseofulvin was investigated using a half two level-four factor factorial design. The granules were characterized using powder XRD, DSC and SEM techniques. A significant enhancement in the in vitro dissolution profiles of the granules was observed compared to the pure drug and drug excipient physical mixtures. The factorial design results indicated that higher drug loading and the presence of HPMC reduced the extent of dissolution of the drug, whereas, the presence of starch enhanced the dissolution rate. XRD data confirmed crystalline drug in formulation matrices. DSC results indicated monotectic mixtures of griseofulvin with PEG in the granulated formulations. In conclusion, the results of this work suggest that melt granulation is a useful technique to enhance the dissolution rate of poorly water-soluble drugs, such as, griseofulvin.

Antifungal Agents↗

Recognition of the tumor suppressor protein p53 and other protein targets by the calcium-binding protein S100B.

S100B is an EF-hand containing calcium-binding protein of the S100 protein family that exerts its biological effect by binding and affecting various target proteins. A consensus sequence for S100B target proteins was published as (K/R)(L/I)xWxxIL and matches a region in the actin capping protein CapZ (V.V. Ivanenkov, G.A. Jamieson, Jr., E. Gruenstein, R.V. Dimlich, Characterization of S-100b binding epitopes. Identification of a novel target, the actin capping protein, CapZ, J. Biol. Chem. 270 (1995) 14651-14658). Several additional S100B targets are known including p53, a nuclear Dbf2 related (NDR) kinase, the RAGE receptor, neuromodulin, protein kinase C, and others. Examining the binding sites of such targets and new protein sequence searches provided additional potential target proteins for S100B including Hdm2 and Hdm4, which were both found to bind S100B in a calcium-dependent manner. The interaction between S100B and the Hdm2 and/or the Hdm4 proteins may be important physiologically in light of evidence that like Hdm2, S100B also contributes to lowering protein levels of the tumor suppressor protein, p53. For the S100B-p53 interaction, it was found that phosphorylation of specific serine and/or threonine residues reduces the affinity of the S100B-p53 interaction by as much as an order of magnitude, and is important for protecting p53 from S100B-dependent down-regulation, a scenario that is similar to what is found for the Hdm2-p53 complex.

Amino Acid Sequence↗

Induction and termination of prepupal summer diapause in Pseudopidorus fasciata (Lepidoptera: Zygaenidae).

The seasonal life cycle of the zygaenid moth, Pseudopidorus fasciata is complicated by two different developmental arrests: a winter diapause as a fourth larval instar and a summer diapause as a prepupa in a cocoon. Both larval diapause induction and termination are under photoperiodic control. Short days induce larval diapause with a critical daylength of 13.5h and long days terminate diapause with a critical daylength of 14h. In the present study photoperiodic control of summer diapause was investigated in Pseudopidorus fasciata. Under long photoperiods ranging from LD 14:10 to LD 18:6, only part of the population entered summer diapause, the rest continued to develop. The lowest number of prepupae entered diapause at LD 14:10, followed by LD 16:8 and LD 17:7. The highest incidence of diapause occurred with photoperiods of LD 15:9 and LD 18:6. By transferring the diapausing prepupae induced by various long photoperiods (LD 14:10, LD 15:9, LD 16:8, LD 17:7, LD 18:6) to LD 13:11, 25 degrees C, the duration of diapause induced by LD 14:10 was significantly shorter than those induced by longer photoperiods. By keeping aestivating prepupae induced by LD 15:9, 28 degrees C or by natural conditions at short photoperiods (LD 11:13 and LD 13:11) and at a long photoperiod (LD 15:9), the duration of diapause at LD 15:9 was more than twice as long as than those at LD 11:13 and LD 13:11. Moreover, adult emergence was highly dispersed with a high mortality at LD 15:9 but was synchronized with low mortality at LD 11:13 and LD 13:11. When the naturally induced aestivating prepupae were kept under natural conditions, the early aestivating prepupae formed in May exhibited a long duration of diapause (mean 126 days), whereas the later-aestivating prepupae formed in July exhibited a short duration of diapause (mean 69 days). These results indicate that aestivating prepupae require short or shortening photoperiod to terminate their diapause successfully. By transferring naturally induced aestivating prepupae to 25, 28 and 30 degrees C, the duration of diapause at the high temperature of 30 degrees C was significantly longer than those at 25 and 28 degrees C, suggesting that high temperature during summer also plays an important role in the maintenance of summer diapause in Pseudopidorus fasciata. All results reveal that summer diapause can serve as a "bet hedging" against unpredictable risks due to fluctuating environments or as a feedback mechanism to synchronize the period of autumn emergence.

Animals↗

Molecular determinants in targeted therapy for esophageal adenocarcinoma.

HYPOTHESIS: Cyclooxygenase 2 (COX-2), vascular endothelial growth factor (VEGF), and epidermal growth factor receptor (EGFR) are useful biological determinants in targeted therapy for esophageal adenocarcinoma. DESIGN: Prospective analysis. SETTING: University tertiary referral center. PATIENTS: Sixteen patients with squamous mucosa and normal results of a pH study without mucosal injury (control group), 15 with Barrett esophagus (metaplasia group), and 44 with adenocarcinoma (carcinoma group). INTERVENTIONS: Biopsy specimens were obtained 3 cm above the gastroesophageal junction. Dysplastic tissue was additionally isolated from 9 of the patients in the carcinoma group. After laser-capture microdissection, quantitative real-time polymerase chain reaction was used to measure gene expression across the spectrum of the metaplasia-dysplasia-carcinoma sequence. MAIN OUTCOME MEASURES: Expression of COX-2, VEGF, and EGFR in each patient group. RESULTS: Expression of both COX-2 and VEGF was significantly up-regulated in patients with metaplasia, dysplasia, and cancer compared with controls (P<.01). Expression levels of both were significantly higher in cancer than in the metaplasia group (P<.05) and increased sequentially from metaplasia to dysplasia to cancer. Expression of VEGF was significantly higher in the dysplastic tissue than in nondysplastic Barrett epithelium (P<.05). No change in expression levels of EGFR was seen in the histologic progression to esophageal adenocarcinoma. CONCLUSION: Gene expression data suggest that pharmacologic inhibition of COX-2 and VEGF may be useful adjuncts in targeted therapy for esophageal adenocarcinoma.

Adenocarcinoma↗

[Preparation of new lipid-hydroxyapatite-DNA complex and gene transfection reseach in eukaryotic cell].

This work was directed at obtaining a better gene carrier to improve the effects of gene delivery. Neutral liposomes made from cholesterol, lecithin and DOPE by reverse evaporation technique were used for encapsulating DNA-HAP complex which was made from DNA and optimized HAP. The sizes of complexes and the efficiency of encapsulation were detected. The efficiency of transfection into Hela cells was shown by observation of X-gal staining and measurement of transfection efficience. The average size of complexes was 643nm, the average encapsulating efficiency of DNA in microspheres reached 11.67%. These Lipid-Hydroxyapatite-DNA complex (LHD) could be transfected into mammalian cells. The Lipid-Hydroxyapatite-DNA complex prepared by reverse evaporation technique could be applied availably in DNA delivery system, and it gave another thinking to increase the gene transfection of non- viral genetic vector.

DNA↗

Irreversibility for all bound entangled states.

We derive a new inequality for entanglement for a mixed four-partite state. Employing this inequality, we present a one-shot lower bound for entanglement cost and prove that entanglement cost is strictly larger than zero for any entangled state. We demonstrate that irreversibility occurs in the process of formation for all nondistillable entangled states. In this way we solve a long standing problem of how "real" is entanglement of bound entangled states. Using the new inequality we also prove the impossibility of local cloning of a known entangled state.

Journal Article↗

Simultaneous detection of isoniazid, rifampin, and ethambutol resistance of Mycobacterium tuberculosis by a single multiplex allele-specific polymerase chain reaction (PCR) assay.

Prompt detection of drug resistance of Mycobacterium tuberculosis is essential for effective control of tuberculosis (TB). We developed a multiplex allele-specific polymerase chain reaction (MAS-PCR) that detects the most commonly observed isoniazid (INH), rifampin (RIF), and ethambutol resistance-associated mutations in a single assay. The usefulness of the newly developed method was evaluated with 174 clinical isolates of M. tuberculosis obtained from Turkey. Distinct PCR banding patterns were observed for different mutation profiles and the correlation between MAS-PCR results and DNA sequencing findings was 99.4%. With culture-based phenotypic drug susceptibility testing as a reference standard, the sensitivity and specificity of the newly developed MAS-PCR assay for drug resistance-related genetic mutation detection were determined to be 81.1% and 97.5% for INH, 93.0% and 98.9 % for RIF, and 54.5% and 68.0 % for ethambutol. MAS-PCR provides a rapid, potentially more cost-effective, method of detecting multidrug-resistant TB.

Alleles↗

Photoperiodic control of diapause in Pseudopidorus fasciata (Lepidoptera: Zygaenidae) based on a qualitative time measurement.

In the zygaenid moth, Pseudopidorus fasciata, both larval diapause induction and termination are under photoperiodic control. In this study, we investigated whether photoperiodic time measurement (with a 24-h light-dark cycle) in this moth is qualitative or quantitative. Photoperiodic response curves, at 22, 25, and 28 degrees C indicated that the incidence of diapause depended on whether the scotophases exceeded the critical night length (CNL) or not. All scotophases longer than the CNL-induced diapause; all scotophases shorter than the CNL-inhibited diapause. The CNL was 10.5h at 25 and 28 degrees C, and 10h at 22 degrees C. By transferring from various short photoperiods (LD 8:16, LD 9:15, LD 10:14, LD 11:13, LD 12:12, and LD 13:11) to a long photoperiod (LD 16:8) at different times, the number of light-dark cycles required for 50% diapause induction at 25 degrees C was 7.14 at LD 8:16, 7.2 at LD 9:15, 7.19 at LD 10:14, 7.16 at LD 11:13, and 7.13 at LD 12:12, without showing a significant difference between the treatments. Only at LD 13:11 (near the CNL), the number of light-dark cycles was significantly increased to 7.64. The intensity of diapause induced under different short photoperiods (LD 8:16, LD 9:15, LD 10:14, LD 11:13, and LD 12:12) at 25 degrees C was not significantly different with an average diapause duration of 36 days. The duration of diapause induced under LD 13:11 was significantly reduced to 32 days. All results indicate that the night-lengths are measured as either "long" or "short" compared with some critical value and suggest that photoperiodic time measurement for diapause induction in this moth is based on a qualitative principle.

Analysis of Variance↗

Hypermethylation of CpG island in O6-methylguanine-DNA methyltransferase gene was associated with K-ras G to A mutation in colorectal tumor.

AIM: To investigate the functions of promoter hypermethylation of O6-methylguanine-DNA methyltransferase (MGMT) gene in colorectal tumorigenesis and progression. METHODS: The promoter hypermethylation of MGMT gene was detected in 27 sporadic colorectal adenomas, 62 sporadic colorectal carcinomas and 20 normal colorectal mucosa tissues by methylation-specific PCR. At the same time, the expression of MGMT protein was carried out in the same samples using immunohistochemistry. Mutant-allele-specific amplification was used to detect K-ras G to A point mutation in codon 12. RESULTS: None of the normal colorectal mucosa tissues showed methylated bands. Promoter hypermethylation was detected in 40.7% (11 of 27) of adenomas and 43.5% (27 of 62) of carcinomas. MGMT proteins were expressed in nucleus and cytoplasm of normal colorectal mucosa tissues. Loss of MGMT expression was found in 22.2% (6 of 27) of adenomas and 45.2% (28 of 62) of carcinomas. The difference between them was significant (P = 0.041). In the 6 adenomas and 28 carcinomas losing MGMT expression, 5 and 24 cases presented methylation, respectively (P = 0.027, P<0.001). Thirteen of the 19 colorectal tumors with K-ras G to A point mutation in codon 12 had methylated MGMT (P = 0.011). The frequencies of K-ras G to A point mutation were 35.3% (12 of 34) and 12.7% (7 of 55) in tumors losing MGMT expression and with normal expression, respectively. CONCLUSION: Promoter hypermethylation and loss of expression of MGMT gene were common events in colorectal tumorigenesis, and loss of expression of MGMT occurs more frequently in carcinomas than in adenomas in sporadic patients. Hypermethylation of the CpG island of MGMT gene was associated with loss of MGMT expression and K-ras G to A point mutation in colorectal tumor. The frequency of K-ras G to A point mutation was increased in tumors losing MGMT expression. It suggests that epigenetic inactivation of MGMT plays an important role in colorectal neoplasia.

Colorectal Neoplasms↗

Clinical relevance of Mycobacterium tuberculosis plcD gene mutations.

To identify Mycobacterium tuberculosis virulence factors, we integrated comparative genomics and epidemiologic data analysis to investigate the relationship between certain genomic insertions and deletions in the phospholipase-C gene D (plcD) with the clinical presentation of tuberculosis (TB). Four hundred ninety-six well-characterized M. tuberculosis clinical isolates were studied. Approximately 30% (147) of the isolates had an interruption of the plcD gene. Patients infected with the plcD mutant were twice as likely to have extrathoracic disease as those infected by a strain without an interruption (adjusted odds ratio, 2.19; 95% confidence interval, 1.27, 3.76). When we limited the analysis to the 275 isolates with distinct DNA fingerprint patterns, we observed the same association (adjusted odds ratio, 2.74; 95% confidence interval, 1.35, 5.56). Furthermore, the magnitude of the association appeared to differ with the type of extrathoracic TB. Our findings suggest that the plcD gene of M. tuberculosis is potentially involved in the pathogenesis of TB, and the clinical presentation of the disease may be influenced by the genetic variability of the plcD region.

Adult↗

Molecular characterization of isoniazid and rifampin resistance of Mycobacterium tuberculosis clinical isolates from Malatya, Turkey.

Molecular characterization of drug resistance of Mycobacterium tuberculosis strains of different origins can generate information useful for developing molecular methods that are widely applicable for rapid drug resistance detection. Using DNA sequencing and allele-specific polymerase chain reaction (AS-PCR), we investigated genetic mutations associated with isoniazid (INH) and rifampin (RIF) resistance among 29 drug-resistant clinical isolates of M. tuberculosis collected from Malatya, Turkey, including 19 multi-drug-resistant (MDR) isolates. Point mutations were detected at codons 531, 516, 526, and 513 of the RNA polymerase beta- subunit gene (rpoB) in 10 (47.6%), five (23.8%), three (14.3%), and three (14.3%) of the 21 RIF-resistant isolates, respectively. Of the five isolates having mutations in codon 516, three also had mutations at codon 527; one had a concurrent mutation at codon 572. Mutations at codon 315 of the catalase-peroxidase-encoding gene (katG) were found in 17 (63.0%) of the 27 INH-resistant isolates. Interestingly, the katG codon 315 mutation was observed at a much higher frequency in MDR isolates than in INH-mono-resistant isolates ( approximately 79% vs. 25%). This study provided the first molecular characterization of INH and RIF resistance of M. tuberculosis clinical isolates from Eastern Turkey, and extended our knowledge of molecular basis of M. tuberculosis drug resistance.

Antitubercular Agents↗

Thermo-mechanical responses of a surface-coupled AFM cantilever.

Atomic force microscopy (AFM) has been widely used for measuring mechanical properties of biological specimens such as cells, DNA, and proteins. This is usually done by monitoring deformations in response to controlled applied forces, which have to be at ultralow levels due to the extreme softness of the specimens. Consequently, such experiments may be susceptible to thermal excitations, manifested as force and displacement fluctuations that could reduce the measurement accuracy. To take advantage of, rather than to be limited by, such fluctuations, we have characterized the thermomechanical responses of an arbitrarily shaped AFM cantilever with the tip coupled to an elastic spring. Our analysis shows that the cantilever and the specimen behave as springs in parallel. This provides a method for determining the elasticity of the specimen by measuring the change in the tip fluctuations in the presence and absence of coupling. For rectangular and V-shaped cantilevers, we have derived a relationship between the mean-square deflection and the mean-square inclination and an approximate expression for the specimen spring constant in terms of contributions to the mean-square inclination from the first few vibration modes.

Computer Simulation↗

The diversity effect of inductive reasoning under segment manipulation of complex cognition.

The present study proposed the idea of segment manipulation of complex cognition (SMCC), and technically made it possible the quantitative treatment and systematical manipulation on the premise diversity. The segment manipulation of complex cognition divides the previous inductive strengths judgment task into three distinct steps, attempting to particularly distinguish the psychological processes and their rules. The results in Experiment 1 showed that compared with the traditional method, the quantitative treatment and systematical manipulation of SMCC on the diversity did not change the task's nature, and remain rational and a good measurement of inductive strength judgment. The results in Experiment 2 showed that the participants' response rules in the triple-step task were expected from our proposal, and that in Step 2 the "feeling of surprise" (FOS), which seems implausible but predicted from the diversity premises, was measured, and its component might be the critical part that produced the diversity effect. The "feeling of surprise" may reflect the impact of emotion on cognition, representing a strong revision to premise probability principle of pure rational hypothesis proposed by Lo et al., and its roles in the diversity effect are worthy of further research. In this regards were discussed the mistakes that the premise probability principle makes when it takes posterity probability as prior probability.

Adult↗

The development of the lymphoid organs of flounder, Paralichthys olivaceus, from hatching to 13 months.

The growth of the lymphoid organs, such as head kidney, spleen and thymus were studied in flounder, Paralichthys olivaceus Temminck & Schlegel, from hatching to 13 months of age. Except for the thymus, all organs grew as the fish grew. By 2 months of age the lymphoid organs attained their maximum relative weight. The organ weight showed a closer correlation to body weight than they did to age. The total number of leucocytes in the lymphoid organs increased with age, but the number per milligram of lymphoid organ remained constant. A micro and ultrastructural study of the lymphoid organs showed that the full development of the lymphoid organs was not achieved until the juvenile stage. The spleen and head kidney had mixed populations of "red" and "white" cells. The head kidney was more lymphoid than the spleen. The thymus involuted quickly during the first 6 months. The blood components had no obvious relationship with age or season during the period studied.

Age Factors↗

[Expression and clinical significance of survivin gene and PTEN protein in colorectal adenocarcinoma].

BACKGROUND & OBJECTIVE: The occurrence of colorectal adenocarcinoma is resulted from multiple factors and both survivin gene and PTEN protein take part in these courses. They all regulate cell cycle and apoptosis, but their biological effects are adverse. It is not completely elucidated about their function and relationship in colorectal adenocarcinoma. This study was designed to investigate the role of survivin gene and PTEN protein in the pathogenesis of colorectal adenocarcinoma and their correlation. METHODS: To determine the survivin mRNA in 42 colorectal adenocarcinoma and 20 adjacent normal colorectal tissue samples, we used reverse transcription polymerase chain reaction (RT-PCR) to determine the expression of survivin mRNA, and immunohistochemical evaluation was used to determine the expression of PTEN protein. RESULTS: The positive expression rate of survivin was 54.8% in colorectal adenocarcinoma, while no expression was detected in adjacent normal tissue. The expression of survivin gene was significantly correlated with histological differentiation and Dukes stage, but not with gender or lymph node metastasis. The positive rate of PTEN protein in colorectal carcinoma was lower (47.6%) than that in adjacent normal tissue (90.0%). The difference between them was significant (P< 0.01). There was no relationship between PTEN protein and gender, while the expression of PTEN was positively correlated with histological differentiation and lymph node metastasis, and possibly correlated with Dukes stage. With the progress of tumor in malignancy, negative correlation was observed between survivin and PTEN expression in colorectal adenocarcinoma. CONCLUSION: Survivin gene and PTEN protein are significantly correlated with the clinicopathological characteristics and biologic behaviors in colorectal adenocarcinoma. Detection of survivin together with PTEN is valuable for diagnosing colorectal adenocarcinoma, and evaluating malignancy extent and prognosis.

Adenocarcinoma↗