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Biomedical subjects

Peng Wu

Publications and source records attributed to Peng Wu.

At least 19 recordsLinked to original sources
PubMed2026

Emerging multidimensional biomarker system for cardiovascular-kidney-metabolic syndrome: from multi-omics integration to clinical artificial intelligence.

Cardiovascular-kidney-metabolic (CKM) syndrome is an emerging clinical entity that highlights the complex, bidirectional interplay among cardiovascular disease, chronic kidney disease, and metabolic disorders, representing a substantial and growing global health burden. This conceptualization marks a paradigm shift from viewing these conditions in isolation to understanding them as an interconnected disease continuum. Traditional biomarkers face significant limitations in the early detection, risk stratification, and precise management of CKM, necessitating a transition towards an integrated framework that captures its multisystem nature. This review systematically outlines an emerging multidimensional biomarker system encompassing key pathological axes such as metabolism, immuno-inflammation, oxidative stress, and biological aging, offering refined risk assessment beyond conventional metrics. The development of this system is propelled by revolutionary platforms, including accessible sampling techniques (e.g., dried blood spots), advanced in vitro models (e.g., multi-organ-on-a-chip), and multi-omics technologies. These platforms not only facilitate a deeper dissection of the heterogeneous origins and inter-organ crosstalk in CKM but also accelerate the discovery and validation of novel biomarkers. Concurrently, artificial intelligence serves as a pivotal tool for clinical translation, effectively integrating high-dimensional data to transform complex molecular profiles into actionable clinical insights. By enabling the construction of dynamic risk prediction and decision-support systems, this review charts a pathway toward proactive, individualized, and precise prevention and management of CKM syndrome.

Humans↗
PubMed2007

Inhibition and structure of Trichomonas vaginalis purine nucleoside phosphorylase with picomolar transition state analogues.

Trichomonas vaginalis is a parasitic protozoan purine auxotroph possessing a unique purine salvage pathway consisting of a bacterial type purine nucleoside phosphorylase (PNP) and a purine nucleoside kinase. Thus, T. vaginalis PNP (TvPNP) functions in the reverse direction relative to the PNPs in other organisms. Immucillin-A (ImmA) and DADMe-Immucillin-A (DADMe-ImmA) are transition state mimics of adenosine with geometric and electrostatic features that resemble early and late transition states of adenosine at the transition state stabilized by TvPNP. ImmA demonstrates slow-onset tight-binding inhibition with TvPNP, to give an equilibrium dissociation constant of 87 pM, an inhibitor release half-time of 17.2 min, and a Km/Kd ratio of 70,100. DADMe-ImmA resembles a late ribooxacarbenium ion transition state for TvPNP to give a dissociation constant of 30 pM, an inhibitor release half-time of 64 min, and a Km/Kd ratio of 203,300. The tight binding of DADMe-ImmA supports a late SN1 transition state. Despite their tight binding to TvPNP, ImmA and DADMe-ImmA are weak inhibitors of human and P. falciparum PNPs. The crystal structures of the TvPNP x ImmA x PO4 and TvPNP x DADMe-ImmA x PO4 ternary complexes differ from previous structures with substrate analogues. The tight binding with DADMe-ImmA is in part due to a 2.7 A ionic interaction between a PO4 oxygen and the N1' cation of the hydroxypyrrolidine and is weaker in the TvPNP x ImmA x PO4 structure at 3.5 A. However, the TvPNP x ImmA x PO4 structure includes hydrogen bonds between the 2'-hydroxyl and the protein that are not present in TvPNP x DADMe-ImmA x PO4. These structures explain why DADMe-ImmA binds tighter than ImmA. Immucillin-H is a 12 nM inhibitor of TvPNP but a 56 pM inhibitor of human PNP. And this difference is explained by isotope-edited difference infrared spectroscopy with [6-18O]ImmH to establish that O6 is the keto tautomer in TvPNP x ImmH x PO4, causing an unfavorable leaving-group interaction.

Adenine↗
PubMed2006

Deletion of the intracellular domain of coxsackie and adenovirus receptor (CAR) enhances the expression of itself and boosts the efficiency of current adenovirus-mediated gene therapy in ovarian cancer cell lines in vitro.

The failure of adenovirus-mediated gene therapy often derives from the absence of coxsackie and adenovirus receptor (CAR) expression in target cells. We hypothesize that the slight up-regulation of CAR expression might boost the effect of adenovirus-mediated gene therapy in ovarian cancer. To test this hypothesis, we transfected full-length and intracellular-domain-deleted (tailless) CAR plasmids into CAR-deficient ovarian cancer cell line SKOV3. We observed significant elevations of the in vitro killing effect of Adv-TK and oncolytic adenovirus-mediated cytopathic effect (CPE) in transfected sub-clones, and tailless-transfected SKOV3 showed higher CAR expressions than full-length CAR-transfected cells. We conclude that the extracellular domain of CAR is essential for adenovirus-based gene therapy and, furthermore, that its intracellular domain might play an important role in the regulation of its own expression.

Adenoviridae Infections↗
PubMed2006

Osmolyte-induced protein folding free energy changes.

Upon addition of protecting osmolyte to an aqueous solution of an intrinsically unstructured protein, spectral observables are often seen to change in a sigmoid fashion as a function of increasing osmolyte concentration. Commonly, such data are analyzed using the linear extrapolation model (LEM), a method that defines a scale from 0%-100% folded species at each osmolyte concentration by means of extending pre- and post-folding baselines into the transition region. Defining the 0%-100% folding scale correctly for each osmolyte is an important part of the analysis, leading to evaluation of the fraction of folded protein existing in the absence of osmolytes. In this study, we used reduced and carboxyamidated RNase T1 (RCAM-T1) as an intrinsically unstructured protein, and determined the thermodynamic stability of RCAM-T1 induced by naturally occurring osmolytes. Because the folded fraction of the protein population determined by experiments of thermal and urea-induced denaturation is nonzero in the absence of osmolytes at 15 degrees C, the commonly used LEM can lead to false values of DeltaG[stackD-->N0] for protein folding due to the arbitrary assumption that the protein is 100% unfolded in the presence of buffer alone. To correct this problem, titration of the protein solution with urea and extrapolating back to zero urea concentration gives the spectral value for 100% denatured protein. With fluorescence as the observable we redefine F/F0 to F/F0extrap = 1.0 and require that the denatured-state baseline have this value as its intercept. By so doing, the 0%-100% scale-corrected DeltaG[D-->N0] values of RCAM-T1 folding in the presence of various osmolytes are then found to be identical, with small error, demonstrating that DeltaG[D-->N0] is independent of the osmolytes used. Such a finding is an important step in validating this quantity derived from the LEM as having the properties expected of an authentic thermodynamic parameter. The rank order of osmolyte efficacies in stabilizing RCAM-T1 is sarcosine > sucrose > sorbitol > proline > betaine > glycerol.

Circular Dichroism↗
PubMed2006

Comparison of hydroxylated print additives on antibody microarray performance.

Various hydroxylated additives were added to antibody print buffers at different concentrations to stabilize printed antibodies during normal array spot desiccation on commercial polymer-coated microarray slides. Polyvinyl alcohol addition to print buffers produced the most regular spot morphologies, homogeneous intra-spot antibody distribution, uniform fluorescence intensity, and improved analyte capture activity, maintained up to 1 month at 4 degrees C for capturing model analytes, anti-human IL-1beta, IL-4, and TNFalpha, on these microarraying slides.

Antibodies↗
PubMed2006

[Relationship between programmed cell death 5 protein expression and prognosis of renal clear cell carcinoma].

OBJECTIVE: To study the role of programmed cell death 5 (PDCD5) protein in the oncogenesis and development of renal clear cell carcinoma and its association with the prognosis of the malignancy. METHODS: PDCD5 expression was assayed immunohistochemically in 46 cases of human renal clear cell carcinoma, and the patients' survival was followed up. RESULTS: PDCD5 staining in the adjacent normal tissue of the tumor was significantly stronger than that in the tumor tissue, and PDCD5 expression was significantly correlated with the tumor grade, stage and prognosis. The tumors of high grade with strong invasive ability had much less PDCD5 expression and lighter staining. The three- or five-year survival rates of patients positive for PDCD5 expression was much higher than that of patients negative for PDCD5 expression. CONCLUSION: PDCD5 is a potent inhibitor of malignant transformation of renal clear cell carcinoma and may serve as a major predictor for evaluating the malignant potential and prognosis of the tumor.

Adult↗
PubMed2005

Drug/device combinations for local drug therapies and infection prophylaxis.

Combination devices-those comprising drug releasing components together with functional prosthetic implants-represent a versatile, emerging clinical technology promising to provide functional improvements to implant devices in several classes. Landmark antimicrobial catheters and the drug-eluting stent have heralded the entrance, and significantly, routes to FDA approval, for these devices into clinical practice. This review describes recent strategies creating implantable combination devices. Most prominent are new combination devices representing current orthopedic and cardiovascular implants with new added capabilities from on-board or directly associated drug delivery systems are now under development. Wound coverings and implantable sensors will also benefit from this combination enhancement. Infection mitigation, a common problem with implantable devices, is a current primary focus. On-going progress in cell-based therapeutics, progenitor cell exploitation, growth factor delivery and advanced formulation strategies will provide a more general and versatile basis for advanced combination device strategies. These seek to improve tissue-device integration and functional tissue regeneration. Future combination devices might best be completely re-designed de novo to deliver multiple bioactive agents over several spatial and temporal scales to enhance prosthetic device function, instead of the current 'add-on' approach to existing implant device designs never originally intending to function in tandem with drug delivery systems.

Animals↗
PubMed2005

Role of hTERT in apoptosis of cervical cancer induced by histone deacetylase inhibitor.

Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase holoenzyme as well as the rate-limiting component of the telomerase enzyme complex. However, the role of the hTERT in apoptosis induced by histone deacetylase inhibitor has only been marginally addressed. For the first time, our study demonstrated that trichostatin A (TSA) briefly activated the proliferation of cervical cancer cell lines, HeLa and SiHa, within 12 h, but then inhibited cell growth after that time point. In response to TSA, hTERT expression, telomerase activity, and telomere length also underwent similar changes during the same time frame. Furthermore, the data in our study showed that cells transfected with dominant negative hTERT were more likely to undergo apoptosis induced by TSA than cells transfected with wild-type hTERT. The cyclin/cdk inhibitor p21waf1 was down-regulated by hTERT without changing the expression of p53. Results from this study suggest that the hTERT might be a primary target of TSA and the anti-apoptosis effect of hTERT might be carried out through a p21waf1-dependent and p53-independent pathway.

Apoptosis↗
PubMed2005

One-pot copper(I)-catalyzed synthesis of 3,5-disubstituted isoxazoles.

[reaction: see text] 3,5-Disubstituted isoxazoles are obtained in good yields by a convenient one-pot, three-step procedure utilizing a regioselective copper(I)-catalyzed cycloaddition reaction between in situ generated nitrile oxides and terminal acetylenes. Most functional groups do not interfere with the reaction, which can be performed in aqueous solvents without protection from oxygen. Since all reagents are used in stoichiometric amounts, formation of byproducts is minimized.

Catalysis↗
PubMed2005

Regulation of NK cell activation by stimulatory and inhibitory receptors in tumor escape from innate immunity.

Recent years have witnessed our major progresses in understanding the membrane-bound receptors on NK cells. Although functional studies of ligands for these NK cell receptors provide good opportunities to study roles of NK cells in anti-tumor and anti-virus immunosurveillance, little was known about how these ligands expression were modulated under physiological and pathological conditions. Several recognition models have been proposed to explain such an issue, which include "missing-self", "induced-self" and "modified-self" recognition model. Here stimulatory immunoreceptor mediated NK cell activation will be reviewed, and possible recognition mechanism by which NK cells operate during interaction with target cells will be discussed in details. Tumor escape from NK cell-mediated immunosurveillance will also be further addressed.

Humans↗
PubMed2005

Analysis of human multidrug resistance protein 1 (ABCC1) by matrix-assisted laser desorption ionization/time of flight mass spectrometry: toward identification of leukotriene C4 binding sites.

Multidrug resistance in tumor cells may be caused by reduced drug accumulation resulting from expression of one or more proteins belonging to the ATP-binding cassette (ABC) transporter superfamily. In addition to their drug efflux properties, certain ABC proteins such as multidrug resistance protein 1 (MRP1) (ABCC1) mediate the ATP-dependent transport of a broad array of organic anions. The intrinsically photoreactive glutathione-conjugated cysteinyl leukotriene C4 (LTC4) is a high-affinity physiological substrate of MRP1 and is widely regarded as a model compound for evaluating the substrate binding and transport properties of wild-type and mutant forms of the transporter. In the present study, we have optimized high-level expression of recombinant human MRP1 in Pichia pastoris and developed a two-step purification scheme that results in purification of the transporter to >90% homogeneity. Peptide mapping by matrix-assisted laser desorption ionization/time of flight mass spectrometry of the peptides generated by in-gel protease digestions of purified underglycosylated MRP1 identified 96.7% of the MRP1 sequence with >98% coverage of its 17 transmembrane helices. Subsequent comparisons with mass spectra of MRP1 photolabeled with LTC4 identified six candidate LTC4-modified peptide fragments that are consistent with the conclusion that the intracellular juxtamembrane positions of transmembrane helices 6, 7, 10, 17, and a COOH-proximal portion of the cytoplasmic loop that links the first and second membrane spanning domains are part of the LTC4 binding site of the transporter. Our studies confirm the usefulness of mass spectrometry for analysis of mammalian polytopic membrane proteins and for identification of substrate binding sites of human MRP1.

Adenosine Triphosphate↗
PubMed2005

DNA and protein microarray printing on silicon nitride waveguide surfaces.

Sputtered silicon nitride optical waveguide surfaces were silanized and modified with a hetero-bifunctional crosslinker to facilitate thiol-reactive immobilization of contact-printed DNA probe oligonucleotides, streptavidin and murine anti-human interleukin-1 beta capture agents in microarray formats. X-ray photoelectron spectroscopy (XPS) was used to characterize each reaction sequence on the native silicon oxynitride surface. Thiol-terminated DNA probe oligonucleotides exhibited substantially higher surface printing immobilization and target hybridization efficiencies than non-thiolated DNA probe oligonucleotides: strong fluorescence signals from target DNA hybridization supported successful DNA oligonucleotide probe microarray fabrication and specific capture bioactivity. Analogously printed arrays of thiolated streptavidin and non-thiolated streptavidin did not exhibit noticeable differences in either surface immobilization or analyte capture assay signals. Non-thiolated anti-human interleukin-1 beta printed on modified silicon nitride surfaces reactive to thiol chemistry exhibited comparable performance for capturing human interleukin-1 beta analyte to commercial amine-reactive microarraying polymer surfaces in sandwich immunoassays, indicating substantial non-specific antibody-surface capture responsible for analyte capture signal.

Biosensing Techniques↗
PubMed2005

DNA-based biosensor for monitoring pH in vitro and in living cells.

DNA is a promising material for the construction of a biosensor or bioindicator because its structure is sensitive to the binding of cofactors. In the current studies, we found that a combination of two DNA oligonucleotides, 5'-TCTTTCTCTTCT-3' and 5'-AGAAAGAGAAGA-3', exhibit a novel structural transition from a Watson-Crick antiparallel duplex to a parallel Hoogsteen duplex as the pH changes from pH 7.0 to 5.0. By labeling this DNA for fluorescence resonance energy transfer, we were able to develop a sensitive pH indicator that can detect changes between pH 7.0 and 5.0. Moreover, using DNA-based hairpin parallel-stranded duplex in conjunction with fluorescence microscopy, we were able to observe the pH changes in living cells during apoptosis as an easily detected change in color. These results indicate that the DNA-based pH indicator should be useful for detecting pH changes between pH 7.0 and 5.0 in living cells.

Base Pairing↗
PubMed2005

Automation of liquid-liquid extraction-spectrophotometry using prolonged pseudo-liquid drops and handheld CCD for speciation of Cr(VI) and Cr(III) in water samples.

A simple spectrophotometric system, based on a prolonged pseudo-liquid drop device as an optical cell and a handheld charge coupled device (CCD) as a detector, was constructed for automatic liquid-liquid extraction and spectrophotometric speciation of trace Cr(VI) and Cr(III) in water samples. A tungsten halogen lamp was used as the light source, and a laboratory-constructed T-tube with two open ends was used to form the prolonged pseudo-liquid drop inside the tube. In the medium of perchloric acid solution, Cr(VI) reacted with 1,5-diphenylcarbazide (DPC); the formed complex was automatically extracted into n-pentanol, with a preconcentration ratio of about 5. The organic phase with extracted chromium complex was then pumped through the optical cell for absorbance measurement at 548 nm. Under optimal conditions, the calibration curve was linear in the range of 7.5 - 350 microg L(-1), with a correlation coefficient of 0.9993. The limit of detection (3sigma) was 7.5 microg L(-1). That Cr(III) species cannot react with DPC, but can be oxidized to Cr(VI) prior to determination, is the basis of the speciation analysis. The proposed speciation analysis was sensitive, yet simple, labor-effective, and cost-effective. It has been preliminarily applied for the speciation of Cr(VI) and Cr(III) in spiked river and tap water samples. It can also be used for other automatic liquid-liquid extraction-spectrophotometric determinations.

Automation↗
PubMed2005

[Nephron-sparing surgery for small renal cell carcinoma: clinical analysis of 21 cases].

OBJECTIVE: To evaluate the clinical effects of nephron-sparing surgery in patients with early-stage small renal cell carcinoma. METHODS: Nephron-sparing surgery was performed in 21 patients with renal cell carcinoma including 1 with solitary kidney, 3 with unilateral tumor and contralateral renal compromise, and 17 with unilateral tumor and normal contralateral kidney. The diameter of the tumors ranged from 1.5 to 6.0 cm, with a mean of 2.8 cm. The tumor diameter in 17 patients with normal contralateral kidney was less than 4 cm (mean 2.5 cm) and the average diameter in 4 patients with contralateral renal compromise was 4.2 cm. Sixteen cases were in stage T(1), 4 in stage T(2), and 1 in stage T(3). Of the 21 patients, 4 underwent tumor enucleation, 10 polar nephrectomy and 7 wedge resection. RESULTS: All patients were followed up for an average of 40.8 months (7 to 66 months). One patient suffered a right lung and mediastinum metastasis 3 years after the surgery later and 1 with chronic glomerulonephritis required dialysis 27 months after the operation. No surgical complication or local recurrence were found in other patients. CONCLUSION: As a safe and effective therapy for early-stage small renal cell carcinoma, nephron-sparing surgery can be considered as the gold-standard therapy for patients with lesions less than 4 cm in T(1) and T(2) stages of localized unilateral tumor with normal contralateral kidney.

Adult↗
PubMed2005

[Expression of human telomerase reverse transcriptase in cervix cancer and its significance].

OBJECTIVE: To investigate the expression of human telomerase reverse transcriptase (hTERT) mRNA and protein in cervix cancer, cervical intraepithelial neoplasia (CIN) and normal cervix. METHODS: Expression of hTERT mRNA and the other two subunits of telomerase, human telomerase RNA component (hTR), human telomerase-associated protein (hTP1) was determined by RT-PCR in 3 cervix cancer cell lines, 2 diploid cell lines, 38 cases of cervix cancer, 16 cases of CIN and 20 cases of normal cervix. Telomerase activity was also examined by telomeric repeat amplification protocol enzyme-linked immunosorbent assay (TRAP-ELISA). Expression of hTERT protein was detected in all the cell lines and 101 cases of paraffinized cervix tissue sections. RESULTS: hTERT mRNA expression was detected in all of the three cervix cancer cell lines, 81.6% of cervix cancer, 37.5% of CIN, 5.0% of normal cervix, while in neither of the two diploid cell lines. The other two subunits of telomerase were prevalently expressed in all of the cell lines and most cervix tissues. There was a strong correlation between hTERT mRNA expression and telomerase activity. Immunostaining also revealed that hTERT protein was expressed in all three cervix cancer cell lines, 65.5% of cervix cancer, 28.0% of CIN and 4.8% of normal cervix. CONCLUSION: Up-regulation of hTERT may play an important role in the development of CIN and cervix cancer, hTERT could be used as an early diagnostic biomarker for cervix cancer.

Carrier Proteins↗