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Ping Yu

Publications and source records attributed to Ping Yu.

At least 19 recordsLinked to original sources
PubMed2025

Structural investigation of an RNA device that regulates PD-1 expression in mammalian cells.

Synthetic RNA devices are engineered to control gene expression and offer great potential in both biotechnology and clinical applications. Here, we present multidisciplinary structural and biochemical data for a tetracycline (Tc)-responsive RNA device (D43) in both ligand-free and bound states, providing a structure-dynamical basis for signal transmission. Activation of self-cleavage is achieved via ligand-induced conformational and dynamical changes that stabilize the elongated bridging helix harboring the communication module, which drives proper coordination of the catalytic residues. We then show the utility of CRISPR-integrated D43 in EL4 lymphocytes to regulate programmed cell death protein 1 (PD-1), a key receptor of immune checkpoints. Treatment of these cells with Tc showed a dose-dependent reduction in PD-1 by immunostaining and a decrease in messenger RNA levels by quantitative PCR as compared with wild type. PD-1 expression was recoverable upon removal of Tc. These results provide mechanistic insight into RNA devices with potential for cancer immunotherapy or other applications.

Programmed Cell Death 1 Receptor↗
PubMed2007

Induced sensitization of tumor stroma leads to eradication of established cancer by T cells.

Targeting cancer cells, as well as the nonmalignant stromal cells cross-presenting the tumor antigen (Ag), can lead to the complete destruction of well-established solid tumors by adoptively transferred Ag-specific cytotoxic T lymphocytes (CTLs). If, however, cancer cells express only low levels of the Ag, then stromal cells are not destroyed, and the tumor escapes as Ag loss variants. We show that treating well-established tumors expressing low levels of Ag with local irradiation or a chemotherapeutic drug causes sufficient release of Ag to sensitize stromal cells for destruction by CTLs. This was shown directly using high affinity T cell receptor tetramers for visualizing the transient appearance of tumor-specific peptide-MHC complexes on stromal cells. Maximum loading of tumor stroma with cancer Ag occurred 2 d after treatment and coincided with the optimal time for T cell transfer. Under these conditions, tumor rejection was complete. These findings may set the stage for developing rational clinical protocols for combining irradiation or chemotherapy with CTL therapy.

Adoptive Transfer↗
PubMed2007

Objective voice analysis in dysphonic patients: new data including nonlinear measurements.

OBJECTIVES/HYPOTHESIS: This report describes a comparative study of objective voice evaluation using a multiparametric protocol including aerodynamic parameters and linear and nonlinear acoustic parameters recorded on an EVA(R) workstation and perceptual voice analysis by a jury. STUDY DESIGN: A total of 449 samples were retrospectively selected including 391 patients with pathological voices (308 women and 141 men) and 58 controls with normal voices (38 women and 20 men). A prospective complementary study concerning 43 female patients and 3 controls is presented. METHODS: Objective measures included fundamental frequency (Fo), intensity, jitter, signal-to-noise ratio (SNR), Lyapunov coefficient (Lya), oral airflow (OAF), estimated subglottic pressure (ESGP), maximum phonatory time (MPT) and vocal range. A jury of 4 experienced listeners was instructed to classify voice samples (continuous speech) according to the G (overall dysphonia) component of the GRBAS score on a Visual Analogue Scale (VAS) secondarily transformed in a scale ranging from 0 for normal to 3 for severe dysphonia. RESULTS: It was shown that a nonlinear combination of only 7 parameters in women (vocal range, Lya, ESGP, MPT, OAF, SNR, and Fo) and 6 parameters in men (vocal range, Lya, OAF, ESGP, Fo, SNR) allowed classification of 81% voice samples in the same grade as the jury in women and 84% in men. In the prospective study, 80.5% were correctly classified with the same set of objective measurements. DISCUSSION: The relative importance of the different objective parameters in this type of discriminant analysis is dealt with. Special emphasis is placed on Lya.

Adult↗
PubMed2006

A new approach to the production of the recombinant SOD protein by methylotrophic Pichia pastoris.

The gene for the copper, zinc-superoxide dismutase (SOD) from the yeast Saccharomyces cerevisiae was cloned, characterized, and overexpressed in the methylotrophic Pichia pastoris. The sod gene sequence obtained is 465 bp and encodes 154 amino acid residues. The sod gene sequence was cloned into the pPIC9K vector, yielding pAB22. The linearized pAB22 DNA, digested with restriction enzyme SacI, was transformed into the genome of the GS115 strain of yeast P. pastoris. The overexpressed SOD protein was shown to have immunologically biological activity and to be enzymatically active. The SOD protein was purified from the cultured yeast by ammonium sulfate precipitation and diethylaminoethyl-cellulose column chromatography. This relatively simple purification method produced a single band on analysis by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), which indicated that the SOD protein obtained attained to higher purity and specific activity.

Amino Acid Sequence↗
PubMed2006

Low-frequency cooperative dynamics in L-, D-, and DL-alanine crystals: a 13C and 15N cross-polarization magic-angle-spinning NMR study.

Knowledge of the dynamical changes in molecular configurations in various amino acid structures over a wide range of time scales is important since such changes may influence the structural transformations and the diverse biological functionalities of proteins. Using the temperature dependence of the rotating-frame NMR spin-lattice relaxation times T(1rho) of protons as a probe, we have investigated the low-frequency (approximately 60-100 kHz) dynamics in the crystal structures of L-, D-, and DL- alanine (C(12)H(28)O(8)N(4)) polymorphs. The proton relaxation times T(1rho) were obtained from (13)C <-- (1)H and (15)N <-- (1)H cross-polarization magic-angle-spinning NMR experiments over a temperature range of 192-342 K. The data reveal that the time scales of these low-frequency dynamical processes are distinctly different from the localized, high-frequency rotational motion of methyl and amine groups. The strongly asymmetric T(1rho) versus temperature curves and the subtle dynamical differences between the DL-alanine and the L- and d-enantiomorphs indicate that these low-frequency processes are cooperative in nature and are sensitive to molecular packing.

Alanine↗
PubMed2006

RAP uses a histidine switch to regulate its interaction with LRP in the ER and Golgi.

The receptor associated protein (RAP) is an antagonist and molecular chaperone that binds tightly to low-density lipoprotein receptor family members in the endoplasmic reticulum (ER). After escorting these receptors to the Golgi, RAP dissociates from the receptors. The molecular mechanism of the dissociation has been unknown until now. The solution structure of RAP-D3 domain presented here reveals a striking increase in positively charged residues on the surface of this RAP domain due to protonation of solvent-exposed histidine sidechains as the pH is reduced from a near neutral pH of the ER to the acidic pH of the Golgi. Structure-based mutagenesis studies in vitro and in cells confirm that the protonation of histidine residues as a consequence of the pH changes modulate the binding/release of RAP from LRP. This histidine switch may serve as a general mechanism for regulating cell trafficking events.

Alanine↗
PubMed2006

Perfect polar stacking of parallel beloamphiphile layers. Synthesis, structure and solid-state optical properties of the unsymmetrical acetophenone azine DCA.

Extraordinary high degrees of polar order can be achieved by a rational design that involves the polar stacking of parallel beloamphiphile monolayers (PBAM). This strategy is exemplified by the acetophenone azines MCA (4-methoxy-4'-chloroacetophenone azine) and DCA (4-decoxy-4'-chloroacetophenone azine). The beloamphiphile design aims to achieve strong lateral interactions by way of arene-arene, azine-azine, arene-azine and halogen-bonding interactions. Dipole-induced interactions and halogen bonding dominate interlayer interactions and halogen bonding is shown to effect the layer stacking. Crystals of DCA contain PBAMs with perfect polar order and perfect polar layer stacking, while crystals of MCA features perfect polar order only in one of two layers and layer stacking is polar but not entirely perfect. We report the synthesis of the beloamphiphile DCA, its crystal structure, and we present a comparative discussion of the structures and intermolecular interactions of MCA and DCA. Absorbance and photoluminescence measurements have been carried out for solutions of DCA and for DCA crystals. DCA exhibits a broad emission centered at 2.5 eV when excited with UV radiation. The nonlinear optical response was studied by measuring second harmonic generation (SHG). Strong SHG signals have been observed due to the polar alignment and the DCA crystal's NLO response is 34 times larger than that of urea. Optimization of the beloamphiphile and systematic SAR studies of the polar organic crystals, which are now possible for the very first time, will further improve the performance of this new class of functional organic materials. The materials are organic semiconductors and show promise as blue emitters, as nonlinear optical materials and as OLED materials.

Journal Article↗
PubMed2006

CD40 ligation restores cytolytic T lymphocyte response and eliminates fibrosarcoma in the peritoneum of mice lacking CD4+ T cells.

Absence of CD4(+) T cell help has been suggested as a mechanism for failed anti-tumor cytotoxic T lymphocytes (CTL) response. We examined the requirement for CD4(+) T cells to eliminate an immunogenic murine fibrosarcoma (6132A) inoculated into the peritoneal cavity. Immunocompetent C3H mice eliminated both single and repeat intraperitoneal (IP) inoculums, and developed high frequency of 6132A-specific interferon-gamma (IFNgamma)-producing CTL in the peritoneal cavity. Adoptive transfer of peritoneal exudate cells (PEC) isolated from control mice, protected SCID mice from challenge with 6132A. In contrast, CD4 depleted mice had diminished ability to eliminate tumor and succumbed to repeat IP challenges. Mice depleted of CD4(+) T cells lacked tumor-specific IFNgamma producing CTL in the peritoneal cavity. Adoptive transfer of PEC from CD4 depleted mice failed to protect SCID mice from 6132A. However, splenocytes isolated from same CD4 depleted mice prevented tumor growth in SCID mice, suggesting that 6132A-specific CTL response was generated, but was not sustained in the peritoneum. Treating CD4 depleted mice with agonist anti-CD40 antibody, starting on days 3 or 8 after initiating tumor challenge, led to persistence of 6132A-specific IFNgamma producing CTL in the peritoneum, and eliminated 6132A tumor. The findings suggest that CTL can be activated in the absence of CD4(+) T cells, but CD4(+) T cells are required for a persistent CTL response at the tumor site. Exogenous stimulation through CD40 can restore tumor-specific CTL activity to the peritoneum and promote tumor clearance in the absence of CD4(+) T cells.

Adoptive Transfer↗
PubMed2006

The role of stroma in immune recognition and destruction of well-established solid tumors.

Well-established solid tumors (at least 14 days old and >1cm in average diameter) are extremely difficult to eradicate immunologically in mice. Most cancer patients that seek medical attention bear primary or metastatic tumors that have grown for longer and that are larger than the tumors we call established. Therefore, focusing research on the problems of rejecting well-established mouse tumors might help in the development of novel concepts and protocols for destroying tumors in patients. A particular problem with established cancers is that even when treatments induce temporary regression, cancer often recurs. Recent studies suggest that manipulation of the stromal microenvironment of these tumors can induce immune recognition and regression. Furthermore, targeting cancer cells as well as tumor stroma for immune destruction might be needed to prevent recurrence.

Animals↗
PubMed2006

Treatment of malignant biliary obstruction by combined percutaneous transhepatic biliary drainage with local tumor treatment.

AIM: To evaluate the utility of local tumor therapy combined with percutaneous transhepatic biliary drainage (PTBD) for malignant obstructive biliary disease. METHODS: A total of 233 patients with malignant biliary obstruction were treated in our hospital with PTBD by placement of metallic stents and/or plastic tubes. After PTBD, 49 patients accepted brachytherapy or extra-radiation therapy or arterial infusion chemotherapy. The patients were followed up with clinical and radiographic evaluation. The survival and stent patency rate were calculated by Kaplan-Meier survival analysis. RESULTS: Twenty-two patients underwent chemotherapy (11 cases of hepatic carcinoma, 7 cases of pancreatic carcinoma, 4 cases of metastatic lymphadenopathy), and 14 patients received radiotherapy (10 cases of cholangiocarcinoma, 4 cases of pancreatic carcinoma), and 13 patients accepted brachytherapy (7 cases of cholangiocarcinoma, 3 cases of pancreatic carcinoma, 4 cases of metastatic lymphadenopathy). The survival rate of the local tumor treatment group at 1, 3, 6, and 12 months was 97.96%, 95.92%, 89.80%, and 32.59% respectively, longer than that of the non treatment group. The patency rate at 1, 3, 6, and 12 months was 97.96%, 93.86%, 80.93%, and 56.52% respectively. The difference of patency rate was not significant between treatment group and non treatment group. CONCLUSION: Our results suggest that local tumor therapy could prolong the survival time of patients with malignant biliary obstruction, and may improve stent patency.

Adult↗
PubMed2006

Characterization of kynurenine aminotransferase III, a novel member of a phylogenetically conserved KAT family.

Kynurenine aminotransferase (KAT) is an enzyme responsible for synthesis of kynurenic acid (KYNA), a well established neuroprotective and anticonvulsant agent, involved in synaptic transmission and implicated in the pathophysiology of schizophrenia, Huntington's disease and other neurological disorders. We have shown previously that kat2-/- mice had lower hippocampal KYNA levels and were more hyperactive than wild-type mice. However, these abnormalities occur early and are transitory coinciding with restoration of KYNA levels, suggesting that compensatory changes or ontogenetic expression of another unknown homolog may account for the normalization of KYNA levels in the adult kat2-/- mice brain. Here, we report the isolation of a novel KAT molecule, kat3, from mouse and human brain cDNA libraries. The encoded 454 amino acids of human KAT III share 64.8% similarity to that of KAT I and 30.1% to KAT II. Northern blot analysis demonstrated that kat3 mRNA is widely expressed but with higher expression levels in liver, kidney, heart, and neuroendocrine tissues. RT-PCR and Northern analysis showed that kat3 expression starts as early as postnatal day (PND) 7 and peaks in adult. The mRNA level of kat3 and kat1 when measured together is significantly higher at PND 60 in kat2-/- mice than those of wild-type mice indicating possible co-regulation of expression levels. RNA-interference (RNAi) directed towards transcripts for either R03A10.4 or F28H6.3 in Caenorhabditis elegans which are kat1 and kat3 orthologs, respectively, did not result in any gross abnormalities. Our results show that upregulation of kat3 and kat1 may be responsible for the phenotypic rescue on kat2-/- mice.

5' Untranslated Regions↗
PubMed2006

Tumor-infiltrating T lymphocytes: friends or foes?

The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been a longstanding topic of debate. In cases where TILs have improved patient outcome, T lymphocytes are recognized as the main effectors of antitumor immune responses. However, recent studies have revealed that a subset of CD4(+) T cells, referred to as CD4(+)CD25(+) regulatory T cells (Treg), may accumulate in the tumor environment and suppress tumor-specific T-cell responses, thereby hindering tumor rejection. Hence, predicting tumor behavior on the basis of an indiscriminate evaluation of tumor-infiltrating T cells may result in inconsistent prognostic accuracy. The presence of infiltrating CD4(+)CD25(+) Treg may be detrimental to the host defense against the tumor, while the presence of effector T lymphocytes, including CD8(+) T cells and non-regulatory CD4(+) helper T cells may be beneficial. Enhanced recruitment of antitumor effector T lymphocytes to tumor tissue in addition to inhibition of local Treg, may therefore be an ideal target for improving cancer immunotherapy. This article reviews the antitumor functions of T-lymphocytes, with special attention given to CD4(+) regulatory T-cells within the tumor environment.

CD4-Positive T-Lymphocytes↗
PubMed2006

The KOJACH food frequency questionnaire for Chaoshan, China: development and description.

This paper aims to develop a data-based Semi-Quantitative Food Frequency Questionnaire (SQFFQ) covering both urban and rural areas in the Chaoshan region of Guangdong Province, China, for the investigation of relationships between food intake and lifestyle-related diseases among middle-aged Chinese. We recruited 417 subjects from the general population and performed an assessment of the diet, using a 3-day weighed dietary record survey. We employed contribution analysis (CA) and multiple regression analysis (MRA) to select food items covering up to a 90% contribution and a 0.90 R2, respectively. The total number of food items consumed was 523 (443 in the urban and 417 in the rural population) and the intake of 29 nutrients was calculated according to the actual consumption by foods/recipes. The CA selected 233, 194 and 183 foods/recipes for the combined, the urban and the rural areas, respectively, and then 196, 157 and 160 were chosen by the MRA. Finally, 125 foods/recipes were selected for the final questionnaire. The frequencies were classified into eight categories and standard portion sizes were also calculated. For adoption of the area-specific SQFFQ, Validity and reproducibility tests are now planned to determine how the combined SQFFQ performs in actual assessment of disease risk and benefit.

Adult↗
PubMed2006

[Preparation of ondansetron hydrochloride sustained-release tablet evaluation of its and drug release behavior in vitro].

For the purpose of preparing the ondansetron hydrochloride sustained-release tablets and studying the influencing factors, we prepared the ondansetron hydrochloride sustained-release tablets, using hydroxypropylmethylcellose (HPMC) as the matrix material. Then we investigated the effects of the viscosity and amount of HPMC,the sort of fillers, the preparation methods, the alcohol content in adhesives, and the pH of the dissolving solution on the release of ondansetron hydrochloride from sustained-release tablets. On the basis of pharmaceutical preformulation studies,the best formulation and preparation methods were screened out according to orthogonal experiment design method. The release behavior of the tablets followed the Higuchi equation. The viscosity of HPMC,the sort of fillers and the rotation speed had no significant effects on the release of ondansetron hydrochloride sustained-release tablets,while the preparation methods, the alcohol content in adhesives and the pH of the dissolving solution influcenced the release of ondansetron hydrochloride sustained-release tablets significantly. Ondansetron hydrochloride sustained-release tablets had good drug relase behavior for in 12 h in vitro.

Delayed-Action Preparations↗