Biomedical subjects

Jian Wu

Publications and source records attributed to Jian Wu.

At least 19 recordsLinked to original sources

PubMed2026

Malaria and cancer: common features and interactions.

Malaria and cancer are major global health burdens, causing high mortality. While often considered distinct, the two conditions share common features, including continuous cell replication within the body, systemic inflammation, immune modulation and evasion, metabolic reprogramming, endothelial dysfunction, and drug efflux mechanisms. Interestingly, whereas malaria parasite infection promotes Burkitt lymphoma, recent studies in animal models indicate that malaria may activate immune mechanisms against various tumors, thereby improving survival rates. The malaria protein VAR2CSA specifically binds to chondroitin sulfate A in the placenta and metastatic cancer cells, which can be exploited for cancer detection and treatment. Studying the common and unique features of malaria and cancer may facilitate the development of treatment strategies for both diseases.

Humans↗

PubMed2026

Targeting STK17B kinase activates ferroptosis and suppresses drug resistance in multiple myeloma.

The progression of multiple myeloma (MM), an incurable malignancy of plasma cells, is often associated with the suppression of ferroptosis, a type of cell death driven by iron-dependent lipid peroxidation. The mechanisms underlying this suppression remain largely unknown. Here, we identified serine/threonine kinase 17b (STK17B) kinase as a critical suppressor of ferroptosis in MM. Elevated levels of STK17B are associated with poor overall survival in patients with MM, and STK17B expression is significantly higher in relapsed vs newly diagnosed MM cases. We found that inhibiting STK17B in MM cells increased the labile iron pool, enhanced lipid peroxidation, and sensitized cells to conventional anti-MM therapies. Notably, an orally available, in-house-generated STK17B inhibitor induced ferroptosis and significantly reduced tumor growth in MM xenograft mouse models. Mechanistically, proximity labeling assay combined with the phospho-proteomic analysis identified 2 major regulators of iron uptake and transport as direct targets of STK17B: iron-responsive element binding protein 2 (IREB2), and heat shock protein family B member 1 (HSPB1). We demonstrated that STK17B phosphorylates critical regulatory sites on IREB2 (S157) and HSPB1 (S15), thereby modulating the balance between IREB2 and HSPB1 downstream effectors, proferroptotic transferrin receptor, and antiferroptotic ferritin heavy chain proteins. Furthermore, we demonstrated that STK17B indirectly maintains activating phosphorylation of STAT3, a ferroptosis suppressor and a major driver of MM pathobiology. Our findings uncovered a clinically relevant and targetable STK17B-pIREB2S157/pHSPB1S15 signaling axis that suppresses ferroptosis and contributes to drug resistance in MM.

Ferroptosis↗

PubMed2025

Decreased intestinal abundance of Akkermansia muciniphila is associated with metabolic disorders among people living with HIV.

BACKGROUND: Previous studies have shown changes in gut microbiota after human immunodeficiency virus (HIV) infection, but there is limited research linking the gut microbiota of people living with HIV (PLWHIV) to metabolic diseases. METHODS: A total of 103 PLWHIV were followed for 48 weeks of anti-retroviral therapy (ART), with demographic and clinical data collected. Gut microbiome analysis was conducted using metagenomic sequencing of fecal samples from 12 individuals. Nonalcoholic fatty liver disease (NAFLD) was diagnosed based on controlled attenuation parameter (CAP) values of 238 dB/m from liver fibro-scans. Participants were divided based on the presence of metabolic disorders, including NAFLD, overweight, and hyperlipidemia. Akkermansia abundance in stool samples was measured using RT-qPCR, and Pearson correlation and logistic regression were applied for analysis. RESULTS: Metagenomic sequencing revealed a significant decline in gut Akkermansia abundance in PLWHIV with NAFLD. STAMP analysis of public datasets confirmed this decline after HIV infection, while KEGG pathway analysis identified enrichment of metabolism-related genes. A prospective cohort study with 103 PLWHIV followed for 48 weeks validated these findings. Akkermansia abundance was significantly lower in participants with NAFLD, overweight, and hyperlipidemia at baseline, and it emerged as an independent predictor of NAFLD and overweight. Negative correlations were observed between Akkermansia abundance and both CAP values and body mass index (BMI) at baseline and at week 48. At the 48-week follow-up, Akkermansia remained a predictive marker for NAFLD. CONCLUSIONS: Akkermansia abundance was reduced in PLWHIV with metabolic disorders and served as a predictive biomarker for NAFLD progression over 48 weeks of ART.

Humans↗

PubMed2025

Malaria: Factors affecting disease severity, immune evasion mechanisms, and reversal of immune inhibition to enhance vaccine efficacy.

Malaria is a complex parasitic disease caused by species of Plasmodium parasites. Infection with the parasites can lead to a spectrum of symptoms and disease severity, influenced by various parasite, host, and environmental factors. There have been some successes in developing vaccines against the disease recently, but the vaccine efficacies require improvement. Some issues associated with the difficulties in developing a sterile vaccine include high antigenic diversity, switching expression of the immune targets, and inhibition of immune pathways. Current vaccine research focuses on identifying conserved and protective epitopes, developing multivalent vaccines (including the whole parasite), and using more powerful adjuvants. However, overcoming the systematic immune inhibition and immune cell dysfunction/exhaustion may be required before high titers of protective antibodies can be achieved. Increased expression of surface molecules such as CD86 and MHC II on antigen-presenting cells and blocking immune checkpoint pathways (interactions of PD-1 and PD-L1; CTLA-4 and CD80) using small molecules could be a promising approach for enhancing vaccine efficacy. This assay reviews the factors affecting the disease severity, the genetics of host-parasite interaction, immune evasion mechanisms, and approaches potentially to improve host immune response for vaccine development.

Humans↗

PubMed2024

NAD activates olfactory receptor 1386 to regulate type I interferon responses in Plasmodium yoelii YM infection.

Olfactory receptors (Olfr) are G protein-coupled receptors that are normally expressed on olfactory sensory neurons to detect volatile chemicals or odorants. Interestingly, many Olfrs are also expressed in diverse tissues and function in cell-cell recognition, migration, and proliferation as well as immune responses and disease processes. Here, we showed that many Olfr genes were expressed in the mouse spleen, linked to Plasmodium yoelii genetic loci significantly, and/or had genome-wide patterns of LOD scores (GPLSs) similar to those of host Toll-like receptor genes. Expression of specific Olfr genes such as Olfr1386 in HEK293T cells significantly increased luciferase signals driven by IFN-β and NF-κB promoters, with elevated levels of phosphorylated TBK1, IRF3, P38, and JNK. Mice without Olfr1386 were generated using the CRISPR/Cas9 method, and the Olfr1386-/- mice showed significantly lower IFN-α/β levels and longer survival than wild-type (WT) littermates after infection with P. yoelii YM parasites. Inhibition of G protein signaling and P38 activity could affect cyclic AMP-responsive element promoter-driven luciferase signals and IFN-β mRNA levels in HEK293T cells expressing the Olfr1386 gene, respectively. Screening of malaria parasite metabolites identified nicotinamide adenine dinucleotide (NAD) as a potential ligand for Olfr1386, and NAD could stimulate IFN-β responses and phosphorylation of TBK1 and STAT1/2 in RAW264.7 cells. Additionally, parasite RNA (pRNA) could significantly increase Olfr1386 mRNA levels. This study links multiple Olfrs to host immune response pathways, identifies a candidate ligand for Olfr1386, and demonstrates the important roles of Olfr1386 in regulating type I interferon (IFN-I) responses during malaria parasite infections.

Animals↗

PubMed2007

Diagnosis of gastric cancer using decision tree classification of mass spectral data.

Although gastric cancer is the second leading cause of cancer death worldwide, specific and sensitive biomarkers that can be used for its diagnosis are still unavailable. Attempting to improve on current approaches to the serological diagnosis of gastric cancer, we subjected serum samples from 245 individuals (including 127 gastric cancer patients, 100 age- and sex-matched healthy individuals, nine benign gastric lesion patients and nine colorectal cancer patients) for analysis by surface-enhanced laser desorption/ionization (SELDI) mass spectrometry. Peaks were detected with Ciphergen SELDI software version 3.1.1 and analyzed with Biomarker Patterns' software 5.0. We developed a classifier for separating the gastric cancer groups from the healthy groups. Three protein masses with 1468, 3935 and 7560 m/z were selected as a potential 'fingerprint' for the detection of gastric cancer. It was able to distinguish the gastric cancer patients from the health volunteers with a sensitivity of 95.6% and a specificity of 92.0% in the training set. In the blinding set, it was capable of differentiating the gastric cancer samples from the others with a specificity of 88.0%, a sensitivity of 85.3%, and an accuracy of 86.4%. These values were all higher than those achieved in a parallel analysis by measuring serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 together. Therefore, the decision tree analysis of serum proteomic patterns has the potential to be used in gastric cancer diagnosis.

Adolescent↗

PubMed2006

Four-color DNA sequencing by synthesis using cleavable fluorescent nucleotide reversible terminators.

DNA sequencing by synthesis (SBS) on a solid surface during polymerase reaction offers a paradigm to decipher DNA sequences. We report here the construction of such a DNA sequencing system using molecular engineering approaches. In this approach, four nucleotides (A, C, G, T) are modified as reversible terminators by attaching a cleavable fluorophore to the base and capping the 3'-OH group with a small chemically reversible moiety so that they are still recognized by DNA polymerase as substrates. We found that an allyl moiety can be used successfully as a linker to tether a fluorophore to 3'-O-allyl-modified nucleotides, forming chemically cleavable fluorescent nucleotide reversible terminators, 3'-O-allyl-dNTPs-allyl-fluorophore, for application in SBS. The fluorophore and the 3'-O-allyl group on a DNA extension product, which is generated by incorporating 3'-O-allyl-dNTPs-allyl-fluorophore in a polymerase reaction, are removed simultaneously in 30 s by Pd-catalyzed deallylation in aqueous buffer solution. This one-step dual-deallylation reaction thus allows the reinitiation of the polymerase reaction and increases the SBS efficiency. DNA templates consisting of homopolymer regions were accurately sequenced by using this class of fluorescent nucleotide analogues on a DNA chip and a four-color fluorescent scanner.

Base Sequence↗

PubMed2006

Randomly interesterified triacylglycerol containing medium- and long-chain fatty acids stimulates fatty acid metabolism in white adipose tissue of rats.

We have reported previously that randomly interesterified triacylglycerol containing medium- and long-chain fatty acids in the same glycerol molecule (MLCT) resulted in significantly lower body fat accumulation and higher hepatic fatty acid oxidation than from long-chain triacylglycerol (LCT) in rats. To understand the metabolic changes occurring in white adipose tissue, the fatty acid oxidation and synthesis, and the adipocytokine level were measured in rats fed with MLCT or LCT for 2 weeks. In comparison with LCT, MLCT lowered not only the fatty acid synthase and glycerol-3-phosphate dehydrogenase activities in perirenal adipose tissue, but also the serum insulin and leptin levels, in addition to significantly reducing the body fat accumulation. In contrast, fatty acid oxidation measured as the carnitine palmitoyltransferase activity in the tissue was significantly higher in the MLCT-fed rats than in the LCT-fed rats. It seems that the altered fatty acid metabolism in adipose tissue per se was also responsible for the lower adiposity by dietary MLCT.

Adipose Tissue, White↗

PubMed2006

Hydrostatic-pressure-induced porous gallium nitride from nanotube bundles: an ab initio study.

Ab initio calculations show that (5,5) and (6,6) single-walled gallium nitride nanotubes (GaN NTs) in bundles could aggregate spontaneously to form new condensed phases when bundled tubes are close enough under hydrostatic pressure. The new GaN phases have typical porous structures, constructed by alternating tetragons and hexagons around the original tube walls. Owing to the different compatibilities of the chirality of the tube with the symmetry of the array, the new phase formed from (5,5) GaN NT bundles is triclinic and that from (6,6) ones is hexagonal. These porous GaN phases possess tetrahedral bonding corresponding to sp(3) hybridization, different from sp(2) hybridized bonding in individual GaN NTs. The interaction between tubes not only controls the structural transformation but also influences the electronic structure of porous GaN. We expect that the two-dimensional-channeled porous structure of GaN is advantageous for the usage of GaN as the molecular sieve and as the excellent dilute magnetic semiconductor by considerable magnetic doping.

Journal Article↗

PubMed2006

[Multi-slice computed tomography of myocardial bridge and mural coronary artery and clinical significance thereof].

OBJECTIVE: To investigate the diagnosis of myocardial bridge and mural coronary artery (MB-MCA) with multi-slice computed tomography (MSCT) and clinical significance thereof. METHODS: 900 patients suspected as with coronary artery disease (CHD) underwent 64-slice computed tomography performed by 3 radiologists independently. When consistency was obtained among the independent interpretations of the tomogram among them the diagnosis of MB-MCA could be confirmed. The length of MCA and thickness of MB were measured, and the situation of the nearby arteries were observed and recorded. Based on the above mentioned 3 items the reference scoring criteria were established. RESULTS: 180 sites of MB-NCA were found in 167 (18.56%) of the 900 patients, 112 males and 55 females, aged 54.46 (33 - 84). 167 of the 180 sites of MB-MCA were located on the LAD (92.7%). MCA could be covered by MB in a form of semi-circularity (63.89%, 115/180) or circularity (36.11%, 65/180) The length of MCA was 18.7 mm +/- 10.2 mm, and the thickness of MB was 1.7 mm +/- 1.2 mm. 70% of the arteries proximal and/or distal to the MB-MCA were tortuous. Length of MCA < 10 mm, half-surrounding of MB, and smoothness of the proximal and distant vessels were scored as 1; length of MCA of 10 approximately 20 mm, thickness of MB < 1 mm, and tortuousness of the unilateral proximal or distant vessel were scored as 2; and length of MCA > 20 mm, thickness of MB > 1 mm, and tortuousness of the bilateral proximal and distant vessels were scored as 3. Coronary atherosclerosis was found in 88 of the 167 patients (52.69%). No significant correlation was found between coronary atherosclerosis and MB-MCA grade (u = 1.234, P > 0.05). CONCLUSION: Sixty-four-slice CT can be used to confirm the presence of MB = MCA and the morphology of coronary artery with MB-MCA. Coronary atherosclerosis is not significantly correlated with MB-MCA grade.

Adult↗

PubMed2006

A family of stable silica fullerenes with fully coordinated structures.

Theoretical electronic structure techniques have become an indispensable and powerful tool for predicting molecular properties and designing new materials. The discovery of C(60) opened a challenging field in nanoscale materials science, and since then people have been looking for its inorganic analogues. On the basis of the B3LYP/6-31G(d) calculations, here we provide theoretical evidence for a family of stable silica fullerenes with fully coordinated structures, which exhibit highly structural and energetic stabilities, very large energy gaps, and extremely good resistibilities to breakdown of the insulating capability in an applied electric field. Our calculations indicate that the discrete silica fullerenes are a possible polymorph of silica and can be synthesized under some conditions. They are expected to find novel applications in silica-based molecular devices. The present results may provide an aid in the experimental design for controllably producing desired silica clusters.

Journal Article↗

PubMed2006

Synthesis of steroidal lactone by penicillium citreo-viride.

The biotransformations of a series of steroids by the fungus penicillium citreo-viride A.C.C.C. 0402 have been investigated, and the conversion to the same product testolactone (1) was observed from progesterone (2), dehydroepiandrosterone (3), 4-androstene-3, 17-dione (4), 5-androstene-3, 17-diol (5) with the exception of pregnenolone (6) and 3beta-hydroxy-5, 16-pregnadien-20-one (7). The possible metabolic pathways of the biotransformations were also discussed in the paper and the fungus penicillium citreo-viride A.C.C.C. 0402 was isolated during screening stains from samples collected from Zhengzhou, Henan province of China.

Humans↗

PubMed2006

Cap and capture-release techniques applied to solid-phase synthesis of oligosaccharides.

This paper reports a new strategy for oligosaccharide synthesis by combining solid-phase methods with cap and capture-release separation techniques, using the p-(5-(ethoxycarbonyl)pentyloxy)benzyl group (CPB) as a tag for the capture of desired oligosaccharides. After a complex carbohydrate mixture was obtained by solid-phase synthesis, the desired oligosaccharide containing a free carboxyl group derived from CPB was attached to an amino resin. The loaded resin was readily separated from side products by filtration and finally treated with acid to release the pure oligosaccharide product.

Carbohydrate Conformation↗

PubMed2006

Tremendous spin-splitting effects in open boron nitride nanotubes: application to nanoscale spintronic devices.

Our calculations demonstrate that the intrinsic magnetism of boron nitride nanotubes (BNNTs) can be induced by their open ends, and the resulting magnetic moment is sensitive to the chirality of BNNTs. It is found that BNNTs, a pure sp-electron system, present a tremendous spin-splitting larger than 1 eV and that B-rich-ended and N-rich-ended BNNTs exhibit "conjugate", spin-polarized, deep-gap states. Tremendous spin-splitting effects combined with considerable local spin-polarizations at the open ends make BNNTs significant for applications of nanoscale spintronics such as spin-polarized electron emitters.

Journal Article↗

PubMed2006

An optimal culture condition maintains human hepatocyte phenotype after long-term culture.

BACKGROUND: Long-term culture of primary hepatocytes from various species is impeded by a decrease of cell viability and a loss of hepatocyte-specific function. The aim of the present study was to investigate whether our optimal culture condition (OC) can maintain the phenotype of primary hepatocytes in long-term culture. METHODS: Primary human hepatocytes were cultured in either hepatocyte maintenance medium (HM) or OC for 2-4 weeks. Expression of hepatocyte-specific genes was determined by real-time quantitative RT-PCR. RESULTS: The level of albumin mRNA in human hepatocytes cultured in OC was 11-fold more than in HM and gene expression levels of alpha1-antitrypsin and transferrin were at approximately 40 and 11% of freshly isolated primary human hepatocytes. Electron microscopy revealed that cells in OC displayed hepatocyte properties (e.g. polarity, junctional complexes, bile canaliculi and glycogen particles). Cytochrome P4501A1/2 activity of hepatocytes cultured in OC was 15- and 17-fold higher than in HM at 2 and 4 weeks of culture, and DNA synthesis was higher. CONCLUSIONS: Using our optimal culture condition, we were able to maintain the phenotype of primary human hepatocytes in long-term culture. They not only maintain better liver-specific function, but also retain higher proliferative potential.

Journal Article↗

PubMed2006

Comparison study of atomic and molecular single ionization in the multiphoton ionization regime.

In this Letter, we report, for the first time in the multiphoton ionization regime, a comparison study of single-electron ionization of diatomic molecules versus rare gas atoms with virtually the same ionization potentials. In comparing N2+ to Ar+, a higher ion signal is seen in N2+ compared to Ar+ for linear polarization but the difference vanishes in circularly polarized light. In comparing O2+ to Xe+, we observe a suppression in O2+ compared to Xe+ for both linear and circular polarization but this suppression exhibits an intensity dependence; i.e., there is little suppression for O2+ at the lowest intensity range, but the suppression becomes increasingly stronger as the laser intensity increases. The multielectron screening model is used to discuss possible mechanisms of this intensity dependent suppression in O2+ in the multiphoton ionization regime.

Journal Article↗

PubMed2006

Chemical functionalization of carbon nanotubes by carboxyl groups on stone-wales defects: a density functional theory study.

Chemical functionalization of carbon nanotubes with Stone-Wales (SW) defects by carboxyl (COOH) groups is investigated by density functional calculations. Due to the localized donor states induced by the SW defect, the binding of the COOH group with the defective carbon nanotube is stronger than that with the perfect one. A quasi-tetrahedral bonding configuration of carbon atoms, indicating sp3 hybrid bonding, is formed in the adsorption site. The charge distribution analysis shows that, in comparison with benzoic acid, the localized or delocalized pi states on the nanotube would affect the polarities of chemical bonds of the COOH group without losing the acidity. Furthermore, it is found that the double-adsorption system (two COOH groups are respectively adsorbed on two individual carbon atoms of the SW defect) is more energetically favorable than the monoadsorption one. The adsorption of COOH groups leads to a significant change of the electronic states around the Fermi level, which is advantageous for the electrical conductivity. The functionalization by introducing functional groups on the topological defects provides a pathway for applications of carbon nanotubes in chemical sensors and nanobioelectronics.

Journal Article↗

PubMed2006

Structural, electronic, and magnetic properties of manganese-doped Zn12O12 clusters: a first-principles study.

A first-principles study has been performed to evaluate the structural, electronic, and magnetic properties of Zn(12)O(12) clusters doped with one or two Mn atoms. The substitutional, exohedral, and endohedral dopings are taken into account. For the monodoped clusters, the substitutional isomer is most energetically favorable, and an exohedral isomer may appear as a low-lying metastable state. All isomers present 5 mu(B) magnetic moment that is mainly contributed by the Mn-3d component. For the bidoped clusters, the antiferromagnetic state is degenerate with the ferromagnetic state at larger Mn-Mn distance (>5 A), while it is more energetically favorable at smaller Mn-Mn distance. Thus, the cohesion of bidoped isomer is sensitive to the magnetic coupling or chemical bonding. The endohedral bidoped isomer is found to be a stable local minimum, and the direct Mn-Mn interaction causes the reduction of local magnetic moment of Mn to about 4 mu(B).

Journal Article↗