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Hongtao Liu

Publications and source records attributed to Hongtao Liu.

At least 19 recordsLinked to original sources
PubMed2026

Prolonged Cytopenia After Idecabtagene Vicleucel for Multiple Myeloma is Associated with Poor Overall Survival.

Cytopenias are well-recognized toxicities of idecabtagene vicleucel (ide-cel), a chimeric antigen receptor T cell (CAR-T) therapy approved for the treatment of relapsed, refractory multiple myeloma (RRMM). However, little is known of prognostic implications of cytopenias that persist 30 to 100 days after CAR-T infusion. We report the duration, incidence, and impact on outcomes of post-CAR-T cytopenias at Day 30 and Day 100, defined as an absolute neutrophil count of <500 cells/mm3 and/or platelet count <20 &#xd7; 109 cells/L, per the recent definitions of immune effector cell-associated hematotoxicity for neutropenia (N-ICAHT) and thrombocytopenia (T-ICAHT). Using observational data from the Center for International Blood and Marrow Transplant Research, we identified 821 patients treated during 2021 to 2023. The cumulative incidence of cytopenias at Day 30 was 25% and at Day 100 was 2%. Patients with Day 30 cytopenias had inferior progression-free survival (PFS) (39% versus 45%, P = .01) and overall survival (OS) at 12 months (57% versus 76%, P < .01). While there was no significant difference in PFS in patients who had Day 100 cytopenias (42% versus 53%, P = .12), compared to those who did not, patients with Day 100 cytopenias had significantly inferior OS at 12 months (55% versus 82%, P < .01). High (&#x2265;2) chimeric antigen receptor cell-mediated hematotoxicity score was associated with cytopenias at Day 30 (hazard ratio 5.26, P < .001). Cytopenias at Day 30 after ide-cel were associated with inferior PFS and OS. In addition, cytopenias at Day 100 after ide-cel are rare and are associated with inferior OS.

CAR-T↗
PubMed2006

Full automation of solid-phase microextraction/on-fiber derivatization for simultaneous determination of endocrine-disrupting chemicals and steroid hormones by gas chromatography-mass spectrometry.

A fully automated method using direct immersion solid-phase microextraction (DI-SPME) and headspace on-fiber silylation for simultaneous determinations of exogenous endocrine-disrupting chemicals (EDCs) and endogenous steroid hormones in environmental aqueous and biological samples by gas chromatography-mass spectrometry (GC-MS) was developed and compared to a previously reported manual method. Three EDCs and five endocrine steroid hormones were selected to evaluate this method. The extraction and derivatization time, ion strength, pH, incubation temperature, sample volume, and extraction solvent were optimized. Satisfactory results in pure water were obtained in terms of linearity of calibration curve (R2=0.9932-1.0000), dynamic range (3 orders of magnitude), precision (4-9% RSD), as well as LOD (0.001-0.124 microg L(-1)) and LOQ (0.004-0.413 microg L(-1)), respectively. These results were similar to those obtained using a manual method, and moreover, the precision was improved. This new automated method has been applied to the determinations of target compounds in real samples used in our previous study on a manual SPME method. Exogenous octylphenol (OP), technical grade nonylphenol (t-NP), and diethylstilbestrol (DES) were at 0.13, 5.03, and 0.02 microg L(-1) in river water and 3.76, 13.25, and 0.10 microg L(-1) in fish serum, respectively. Natural steroid hormones estrone (E1), 17beta-estradiol (E2), and testosterone (T) were at 0.19, 0.11, and 6.22 microg L(-1) in river water; and in female fish serum E1, E2, and pregnenolone (PREG) were at 1.37, 1.95, and 6.25 microg L(-1), respectively. These results were confirmed by the manual method. The developed fully automated SPME and on-fiber silylation procedures showed satisfactory applications in environmental analysis and the performances show improved precision and a reduced analysis time compared to the manual method.

Animals↗
PubMed2006

Pb(m)-Phenyl (m = 1-5) complexes: an anion photoelectron spectroscopy and density functional study.

The phenyl-lead metal complexes ([Pb(m)C6H5]-) produced from the reactions between benzene and lead clusters formed by laser ablation on a lead solid sample are studied by photoelectron spectroscopy (PES) and density functional theory (DFT). The adiabatic electron affinities (EAs) of [Pb(m)C6H5]- are obtained from PES at 308 nm, and the differences between the PES of [Pb(m)C6H5]- and the PES of Pbm- are discussed in detail. The results reveal that the phenyl group binds perpendicularly on lead clusters through the Pb-C sigma bond and the complexes have a closed shell structure. Calculations with DFT are carried out on the structural and electronic properties of [Pb(m)C6H5]-, and the adiabatic detachment energy for the optimized structures of anion are in agreement with the experimental PES results. The density of states (DOS) calculated is compared with experimental PES and is discussed. The most possible structures for each species are concluded, and the bonding between Pb and phenyl is analyzed, which also proves that the phenyl group binds perpendicularly on lead clusters through the Pb-C sigma bond.

Journal Article↗
PubMed2006

Experimental and theoretical investigation on binary semiconductor clusters of Bi/Si, Bi/Ge, and Bi/Sn.

Bi(m)M(n)- (M = Si, Ge, Sn) binary cluster anions are generated by using laser ablation on mixtures of Bi and M (M = Si, Ge, Sn) samples and studied by reflectron time-of-flight mass spectrometer (RTOF-MS) in the gas phase. Some magic number clusters are present in the mass spectra which indicate that they are in stable structures. For small anions (m + n < or = 6), their structures are investigated with the DFT method and the energetically lowest lying structures are obtained. For the binary anionic clusters with the same composition containing Si, Ge, and Sn, they share similar geometric and electronic structure in the small size except that BiSi3-, BiSi5-, Bi2Si2-, Bi2Si3-, and Bi4Sn2- are different for the lowest energetic structures, and the ground states for all the anions are in their lowest spin states. The calculated VDE (vertical detachment energy) and binding energy confirm the obviously magic number cluster of BiM4- (M = Si, Ge, Sn), which agrees with the experimental results.

Journal Article↗
PubMed2006

Regulation of Mcl-1 expression in rheumatoid arthritis synovial macrophages.

OBJECTIVE: Resistance to apoptosis may be an important mechanism contributing to the persistence of rheumatoid arthritis (RA). This study was undertaken to characterize the expression, regulation, and function of the antiapoptotic Bcl-2 family member Mcl-1 in macrophages isolated from the joints of patients with RA. METHODS: Mononuclear cells were isolated from the synovial fluid (SF) of patients with RA. Mcl-1 expression was documented by intracellular staining of CD14+ cells using flow cytometry, and by real-time polymerase chain reaction or immunoblot analysis of isolated macrophages. The expression of Mcl-1 was suppressed with small interfering RNA (siRNA) or chemical inhibitors of the phosphatidylinositol 3-kinase (PI 3-kinase)/Akt-1 and signal transducer and activator of transcription 3 (STAT-3) pathways. Apoptosis was defined by the loss of mitochondrial transmembrane potential and by DNA fragmentation. RESULTS: The expression of Mcl-1 was increased in CD14+ macrophages from the SF of patients with RA compared with normal in vitro-differentiated macrophages. Inhibition of the PI 3-kinase/Akt-1 or STAT-3 pathways significantly reduced the percentage of CD14+ cells within the SF and resulted in the reduction of Mcl-1 and the induction of apoptosis of synovial macrophages. Transfection of RA synovial macrophages with Mcl-1 siRNA resulted in apoptotic cell death. CONCLUSION: Mcl-1 is critical for the survival of macrophages in the joints of patients with RA, and is therefore a potential therapeutic target in this disease.

Apoptosis↗
PubMed2006

Reactions of platinum cluster ions with benzene.

In this work, the cation and anion products of the reactions between platinum clusters produced by laser ablation and the benzene molecules seeded in argon have been studied using a high-resolution reflectron time-of-flight mass spectrometer (RTOFMS). The dominant cation products are [C(6n)H(6n - k)](+) and [Pt(m)(C(6)H(6))(n)](+) complexes, while the dominant anion products are dehydrogenated species, [C(6)H(5)PtH](-), [PtC(12)H(k)](-) and [Pt(m)C(6)H(4) . . . (C(6)H(6))(n)](-), etc. Some important intermediate structures ([PtC(6)H(6)](+), [Pt(C(6)H(6))(2)](+), [Pt(2)(C(6)H(6))(3)](+), [C(6)H(5)PtH](-), [Pt(2)C(6)H(4)](-), [Pt(3)C(6)H(4)](-) and [Pt(4)C(6)H(4)](-)) have been analyzed using density functional theory (DFT) calculations. Different reaction mechanisms are proposed for platinum cluster cations and anions with benzene, respectively.

Journal Article↗
PubMed2006

Inhibition of ADP/ATP exchange in receptor-interacting protein-mediated necrosis.

Receptor-interacting protein (RIP) has been implicated in the induction of death receptor-mediated, nonapoptotic cell death. However, the mechanisms remain to be elucidated. Here we show that tumor necrosis factor alpha induced RIP-dependent inhibition of adenine nucleotide translocase (ANT)-conducted transport of ADP into mitochondria, which resulted in reduced ATP and necrotic cell death. The inhibition of ADP/ATP exchange coincided with the loss of interaction between ANT and cyclophilin D and the inability of ANT to adopt the cytosolic conformational state, which prevented cytochrome c release. Neither overexpression of Bcl-xL nor inhibition of reactive oxygen species prevented necrosis. In contrast, the ectopic expression of ANT or cyclophilin D was effective at preventing cell death. These observations demonstrate a novel mechanism initiated through death receptor ligation and mediated by RIP that results in the suppression of ANT activity and necrosis.

Adenosine Diphosphate↗
PubMed2005

Phenyl-coinage metal (Ag, Au) complexes: an anion photoelectron spectroscopy and density functional study.

The important intermediate phenyl-coinage metal complexes (Ag(m)C6H5(-), Au(m)C6H5(-)), which are produced from the reactions between coinage metal clusters formed by laser ablation and the benzene molecules seeded in argon carrier gas, are studied by PES (photoelectron spectroscopy) and DFT (density functional theory). The EAs (adiabatic electron affinities) of these complexes are obtained from PES at both 308 and 193 nm photon energies and show odd-even alternation. Calculations with DFT are carried out on the structural and electronic properties of Ag(m)C6H5(-) and Au(m)C6H5(-); the adiabatic detachment energy and the calculated DOS (density of states) for the ground state of a given anion are in good agreement with the experimental PES results. The observed spectra are also compared with those of the pure coinage metal clusters, which reveal that there are some similarities between them and the phenyl acts like an additional metal atom in the clusters. Furthermore, the bonding between phenyl and metal is analyzed, suggesting that phenyl group binds perpendicularly on metal clusters through C-M sigma bond.

Journal Article↗
PubMed2005

Mcl-1 is essential for the survival of synovial fibroblasts in rheumatoid arthritis.

Mcl-1 is a Bcl-2-family, antiapoptotic molecule that is critical for the survival of T and B lymphocytes and macrophages; however, its role in nonhemopoietic cells remains to be fully elucidated. The current study focuses on the role of Mcl-1 in rheumatoid arthritis (RA). Mcl-1 was strongly expressed in the synovial lining and was increased in the sublining fibroblasts of patients with RA, compared with control synovial tissue. The expression of Mcl-1 in sublining fibroblasts correlated with the degree of inflammation and TNF-alpha, and IL-1beta treatment of cultured synovial fibroblasts resulted in the increased expression of Mcl-1 at the mRNA and protein levels. Mcl-1 was critical for the survival of RA synovial fibroblasts, because the forced reduction of Mcl-1 using a Mcl-1 antisense-expressing adenoviral vector induced apoptotic cell death, which was mediated through Bax, Bak, and Bim. These observations document a critical role for Mcl-1 in protecting against apoptosis in RA and suggest that Mc1-1 is a potential therapeutic target in this disease.

Arthritis, Rheumatoid↗
PubMed2005

Genetic demonstration that the plasma membrane maxianion channel and voltage-dependent anion channels are unrelated proteins.

The maxianion channel is widely expressed in many cell types, where it fulfills a general physiological function as an ATP-conductive gate for cell-to-cell purinergic signaling. Establishing the molecular identity of this channel is crucial to understanding the mechanisms of regulated ATP release. A mitochondrial porin (voltage-dependent anion channel (VDAC)) located in the plasma membrane has long been considered as the molecule underlying the maxianion channel activity, based upon similarities in the biophysical properties of these two channels and the purported presence of VDAC protein in the plasma membrane. We have deleted each of the three genes encoding the VDAC isoforms individually and collectively and demonstrate that maxianion channel (approximately 400 picosiemens) activity in VDAC-deficient mouse fibroblasts is unaltered. The channel activity is similar in VDAC1/VDAC3-double-deficient cells and in double-deficient cells with the VDAC2 protein depleted by RNA interference. VDAC deletion slightly down-regulated, but never abolished, the swelling-induced ATP release. The lack of correlation between VDAC protein expression and maxianion channel activity strongly argues against the long held hypothesis of plasmalemmal VDAC being the maxianion channel.

Adenosine Triphosphate↗
PubMed2005

NF-kappaB protects macrophages from lipopolysaccharide-induced cell death: the role of caspase 8 and receptor-interacting protein.

Macrophages play a pivotal role in the pathogenesis of a variety of diseases. These studies were performed to characterize the mechanisms by which Toll-like receptor 4 (TLR4)-mediated NF-kappaB activation promotes resistance to cell death in macrophages. When NF-kappaB activation was inhibited by a super-repressor, IkappaBalpha, the TLR4 ligand lipopolysaccharide induced the activation of caspase 8, the loss of mitochondrial transmembrane potential (DeltaPsim), and apoptotic cell death in macrophages. The inhibition of caspase 8 activation suppressed DNA fragmentation but failed to protect macrophages against the loss of DeltaPsim and resulted in necrotic cell death. In contrast, the reduction of receptor-interacting protein 1 suppressed the loss of DeltaPsim and inhibited apoptotic cell death. Further, when caspase 8 activation was suppressed, the knock down of receptor-interacting protein inhibited the loss of DeltaPsim and necrotic cell death. These observations demonstrate that following TLR4 ligation by lipopolysaccharide, NF-kappaB is a critical determinant of macrophage life or death, whereas caspase 8 determines the pathway employed.

Apoptosis↗
PubMed2005

Preparation of porous aminopropylsilsesquioxane by a nonhydrolytic sol-gel method in ionic liquid solvent.

The synthesis of porous aminopropylsilsesquioxane (APSS) has been achieved with 1-butyl-3-methylimidazolium hexafluorophosphate (BMIM(+)PF(6-)) ionic liquid (IL) as a template solvent by a nonhydrolytic sol-gel method of 3-aminopropyltrimethoxysilane under mild temperature. By the alteration of the amount of IL or the catalyst, the gels with various specific surface areas ranged from approximately 600 to approximately 1500 m(2) g(-1) were obtained after the remove of IL by calcination, and their N(2) sorption isotherms were typical IV-like isotherms with H2 hysteresis. The average Battett-Jouner-Halenda pore diameters ranged from 3.2 to 5.6 nm. The results demonstrated that BMIM(+)PF(6-) was physically embodied in the silsesquioxane bulk instead of the chemical bonding. Silsesquioxane has promise in catalysis, biosensors, etc. This work would also provide a way for us to prepare a wide variety of materials by using IL as a template solvent.

Journal Article↗
PubMed2004

Electrochemical deposition of silver in room-temperature ionic liquids and its surface-enhanced Raman scattering effect.

The use of room-temperature ionic liquids (RTILs) as media for electrochemical application is very attractive. In this work, the electrochemical deposition of silver was investigated at a glassy carbon electrode in hydrophobic 1-n-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6) and hydrophilic 1-n-butyl-3-methylimidazolium tetrafluoroborate (BMIMBF4) RTILs and in KNO3 aqueous solution by cyclic voltammetric and potentiostatic transient techniques. The voltammograms showed the presence of reduction and oxidation peaks associated with the deposition and dissolution of silver from AgBF4 in both BMIMPF6 and BMIMBF(4), resembling the redox behavior of AgNO3 in KNO3 aqueous solution. A crossover loop was observed in all the cyclic voltammograms of these electrochemical systems, indicating a nucleation process. From the analysis of the experimental current transients, it was shown that the electrochemical deposition process of silver in these media was characteristic of 3D nucleation with diffusion-controlled hemispherical growth, and the silver nucleation closely followed the response predicted for progressive nucleation in BMIMPF6 and instantaneous nucleation in KNO3 aqueous solution, respectively. Compared with these two cases, the electrochemical deposition of silver in BMIMBF4 deviated from both the instantaneous and progressive nucleation models, which could be controlled by mixed kinetics and diffusion. On the basis of the experimental results, it was shown that parameters such as viscosity and water miscibility of RTILs would affect the electrodeposition behavior of silver. Atom force microscopy was employed to probe the surface morphology of the silver deposit, and it showed that the shining electrodeposit of silver was fairly dense and separate nanoclusters of <100 nm were in evidence, corresponding to an island growth model. The strongly enhanced Raman scattering from the monolayer film of 4-mercaptobenzoic acid demonstrated that as-prepared silver nanoparticular film was surface-enhanced Raman scattering (SERS) active. The enhancement factor was calculated to be up to 9.0 x 10(5) and 1.0 x 10(6) for the silver film obtained in BMIMPF6 and BMIMBF4 RTILs, respectively.

Journal Article↗
PubMed2004

Fas ligation on macrophages enhances IL-1R1-Toll-like receptor 4 signaling and promotes chronic inflammation.

The nonapoptotic functions of Fas ligation are incompletely characterized. In contrast to expectations, we show here that Fas-deficient mice developed less-severe collagen-induced arthritis than did control mice. Despite having milder arthritis, Fas-deficient mice had more of the critical pro-inflammatory mediator interleukin-1 beta (IL-1 beta) in their joints, suggesting inefficient activation through IL-1 receptor 1 (IL-1R1) when Fas signaling is deficient. In primary human macrophages and macrophages from Fas- or Fas ligand (FasL)-deficient mice, interruption of Fas-FasL signaling suppressed nuclear factor-kappa B activation and cytokine expression induced by IL-1 beta and lipopolysaccharide. This cross-talk was mediated by the Fas-associated death domain through interaction with myeloid differentiation factor 88. These observations document a unique mechanism whereby Fas-FasL interactions enhance activation through the IL-1R1 or Toll-like receptor 4 pathway, which may contribute to the pathogenesis of chronic arthritis.

Adaptor Proteins, Signal Transducing↗
PubMed2004

TNF-alpha-induced apoptosis of macrophages following inhibition of NF-kappa B: a central role for disruption of mitochondria.

Previously, we established that suppressing the constitutive activation of NF-kappaB in in vitro matured human macrophages resulted in apoptosis initiated by a decrease of the Bcl-2 family member, A1, and the loss of mitochondrial transmembrane potential (Deltapsi(m)). This study was performed to characterize the mechanism of TNF-alpha-induced apoptosis in macrophages following the inhibition of NF-kappaB. The addition of TNF-alpha markedly enhanced the loss of Deltapsi(m) and the induction of apoptotic cell death. Although caspase 8 was activated and contributed to DNA fragmentation, it was not necessary for the TNF-alpha-induced loss of Deltapsi(m). The inhibition of NF-kappaB alone resulted in the release of cytochrome c from the mitochondria, while both cytochrome c and second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI were released following the addition of TNF-alpha. Furthermore, c-Jun N-terminal kinase activation, which was sustained following treatment with TNF-alpha when NF-kappaB was inhibited, contributed to DNA fragmentation. These observations demonstrate that cytochrome c and second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI may be differentially released from the mitochondria, and that the sustained activation of c-Jun N-terminal kinase modulated the DNA fragmentation independent of the loss of Deltapsi(m).

Adjuvants, Immunologic↗
PubMed2004

NF-kappaB-regulated expression of cellular FLIP protects rheumatoid arthritis synovial fibroblasts from tumor necrosis factor alpha-mediated apoptosis.

OBJECTIVE: Little apoptosis has been observed in rheumatoid arthritis (RA) synovial tissues. Tumor necrosis factor alpha (TNFalpha) is expressed in the joints of patients with RA, yet RA synovial fibroblasts are relatively resistant to apoptosis induced by TNFalpha. Recently, we demonstrated that FLIP is highly expressed in the RA joint. These studies were performed to determine if TNFalpha-induced NF-kappaB controls the expression of FLIP long (FLIP(L)) and FLIP short (FLIP(S)) in RA synovial fibroblasts and to determine the role of FLIP in the control of TNFalpha-induced apoptosis. METHODS: RA synovial fibroblasts were isolated from RA synovial tissues and used between passages 3 and 9. RA synovial or control fibroblasts were sham infected or infected with a control adenovirus vector or one expressing the super-repressor IkappaBalpha (srIkappaBalpha). The cells were stimulated with TNFalpha or a control vehicle, and expression of FLIP(L) and FLIP(S) was determined by isoform-specific real-time polymerase chain reaction and Western blot analysis. Cell viability was determined by XTT cleavage, and apoptosis was determined by annexin V staining, DNA fragmentation, and activation of caspases 8 and 3. RESULTS: TNFalpha induced the expression of both isoforms of FLIP messenger RNA (mRNA) in RA synovial fibroblasts; however, FLIP(L) was the dominant isoform detected by Western blot analysis. In control fibroblasts, TNFalpha induced the expression of FLIP(L) and FLIP(S) mRNA and protein. The TNFalpha-induced, but not the basal, expression of FLIP was regulated by NF-kappaB. When NF-kappaB activation was suppressed by the expression of srIkappaBalpha, TNFalpha-mediated apoptosis was induced. TNFalpha-induced apoptotic cell death was mediated by caspase 8 activation and was prevented by the ectopic expression of FLIP(L) or the caspase 8 inhibitor CrmA. CONCLUSION: The TNFalpha-induced, but not the basal, expression of FLIP is regulated by NF-kappaB in RA synovial fibroblasts. The resistance of RA synovial fibroblasts to TNFalpha-induced apoptosis is mediated by the NF-kappaB-regulated expression of FLIP. These observations support the role of NF-kappaB and FLIP as attractive therapeutic targets in RA.

Annexin A5↗
PubMed2004

Apoptosis in rheumatoid arthritis: friend or foe.

A better understanding of the mechanisms that contribute to the resistance of synovial macrophages and fibroblasts to apoptosis will not only provide better insights into the mechanisms contributing to the perpetuation of rheumatoid arthritis (RA) but will also help identify targets for the development of novel, more effective, and long-lasting therapies for the treatment of patients with RA. To avoid toxicity, such as the induction of apoptosis of critical organs, the mechanisms by which these molecules are targeted and therapy delivered must be carefully selected, using the insights obtained from studies characterizing the mechanisms that promote chronic inflammation.

Apoptosis↗