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Hui Zou

Publications and source records attributed to Hui Zou.

16 recordsLinked to original sources
PubMed2026

The emerging landscape of polymerase θ in tumor pathogenesis and precision treatment.

DNA polymerase θ (Polθ) has emerged as a central yet paradoxical regulator of genome stability and tumor progression. Unlike conventional DNA repair factors, Polθ governs an error-prone double-strand break repair pathway-termed theta-mediated end joining (TMEJ)-which becomes essential for survival in homologous recombination (HR)-deficient cancers while simultaneously fueling genomic instability. This review presents a comprehensive and updated synthesis of Polθ's structural architecture, regulatory networks, and context-dependent functions across major malignancies, including ovarian, breast, lung, and colorectal cancers. We highlight recently uncovered mechanisms, such as the iron-FTH1/FTL-POLQ-RAD51 axis in platinum-resistant ovarian cancer, the differential POLQ regulation under methionine restriction in BRCA1-mutant breast cancer, and the identification of germline POLQ mutations defining a novel hereditary colorectal cancer subtype. Beyond DNA repair, we integrate emerging evidence linking Polθ to replication stress tolerance, base excision repair, and immune modulation via type I interferon activation and macrophage polarization. The review also provides a critical evaluation of current Polθ inhibitors-including ART558, RP-6685, novobiocin, and AB25583-focusing on their mechanisms, synthetic lethality profiles, and ability to overcome PARP inhibitor resistance. By bridging molecular mechanisms with tumor biology and therapeutic translation, this review offers a unique framework for understanding Polθ as both a prognostic biomarker and a precision oncology target, with implications for combination therapies involving radiotherapy, immunotherapy, and chemotherapy.

Cancer therapy↗
PubMed2006

Nuclear exclusion of separase prevents cohesin cleavage in interphase cells.

During mitosis, equal transmission of the duplicated chromosomes demands a strict regulation of separase, which cleaves cohesin and triggers sister chromatid separation in anaphase. Vertebrate separase is inhibited by securin and the inhibitory phosphorylation of separase. However, knockout experiments indicate that securin is dispensable and the inhibitory phosphorylation was observed only in M phase cells. This begs the question how cohesin cleavage by separase is prevented in the absence these two mechanisms. Here we show that separase is excluded from cohesin by the nuclear envelope, which forms in telophase and disassembles in mitosis. The exclusion is achieved passively by its large physical mass and may be backed up by the CRM1-dependent nuclear export. A functional NES motif is identified in separase. We demonstrated that the nuclear envelope is sufficient to prevent active separase from cleaving nuclear cohesin. We propose that the nuclear exclusion is important to prevent cohesin cleavage during interphase in the absence of securin and the phosphorylation inhibition.

Active Transport, Cell Nucleus↗
PubMed2006

Controllable fabrication of two-dimensional compound photonic crystals by single-exposure holographic lithography.

We demonstrate an approach of single-exposure holographic lithography for controllable fabrication of large-scale two-dimensional square and hexagonal compound photonic crystals. In the sublattices, both circular and elliptical micropores on a 100 nm scale can be achieved. Theoretical analysis reveals that the inverse structure of a sample possesses a unique complete photonic bandgap pair in high frequency regions. This method is very robust for the general fabrication of complex periodic microstructures on the optical scale.

Journal Article↗
PubMed2006

Regulation of Separase in meiosis: Separase is activated at the metaphase I-II transition in Xenopus oocytes during meiosis.

Separase is a cysteine protease conserved in all eukaryotes and functions to remove sister chromatid cohesion in anaphase by cleaving the SCC1 subunit of the cohesin complex. Separase activity is regulated by its inhibitor securin and by an inhibitory phosphorylation in vertebrates. However, these regulations have never been directly investigated in the meiotic cell cycle of vertebrates. In this study, we cloned the full-length gene encoding Xenopus separase from an oocyte cDNA library. Purified xSeparase can cleave the human alpha-kleisin subunit of cohesin in vitro but cannot bind to hSecurin when these two proteins are coexpressed in 293T cells. Similar to its human counterpart, xSeparase cleaves itself upon activation but at a single site. The cleavage site is conserved with one of the three self-cleavage sites in hSeparase. Using self-cleavage as a reporter for its activation, we demonstrated that xSeparase is transiently activated between the two meioses and may be involved in homolog separation, as is observed in other organisms. Taking advantage of the inability of xSecurin to interact with hSeparase, we demonstrated that CSF extract can reinhibit both full-length and auto-cleaved hSeparase, indicating that inhibition of separase by phosphorylation does occur under physiological conditions. In addition, we found that endogenous xSecurin accumulated in response to progesterone-induced oocyte maturation and was degraded at both anaphase I and II in an APC/C-dependent manner.

Amino Acid Sequence↗
PubMed2006

[Effects of all-trans retinoic acid on phenotype switch and migration of human pulmonary artery smooth muscle cells in vitro and the possible mechanisms].

OBJECTIVE: To investigate the effects of all-trans retinoic acid (atRA) on phenotype switch and migration of human pulmonary artery smooth muscle cells (PASMC) in vitro and the possible mechanisms. METHODS: Cultured human PASMC were divided into 8 groups randomly: group A (control group), group B (vehicle group), group C (treated with 10% fetal cattle serum), group D, group E, group F, group G, and group H (treated with atRA at the concentrations of 0.001 micromol/L, 0.01 micromol/L, 0.1 micromol/L, 1 micromol/L, 10 micromol/L respectively as well as 10% fetal cattle serum). Then, expression of JWA mRNA in human PASMC was detected by reverse transcriptase-polymerase chain reaction (RT-PCR), cell migration was measured using modified Boyden's chamber, and expression of SM-alpha-actin mRNA and protein was detected by RT-PCR and immunohistochemistry respectively. The difference between the groups was analyzed. RESULTS: There was no significant difference in the JWA mRNA expression of human PASMC between group A (0.125 +/- 0.014), group B (0.164 +/- 0.018) and group C (0.164 +/- 0.006), but the JWA mRNA expression in group D (0.326 +/- 0.018), group E (0.440 +/- 0.033), group F (0.460 +/- 0.040), group G (0.589 +/- 0.024) and group H (0.821 +/- 0.050) were significantly higher than those of group A, group B and group C (all P < 0.01). The number of migrating cells in group C (30.4 +/- 7.4) was higher than those in group A (7.2 +/- 1.9) and group B (6.8 +/- 2.3, all P < 0.01), but the number of migrating cells in group D (21.8 +/- 2.9), group E (17.2 +/- 2.3), group F (14.4 +/- 3.5), group G (12.6 +/- 3.4) and group H (8.8 +/- 2.4) was significantly lower than that in group C (all P < 0.01), and there was no significant difference between group G, group H and group A, group B. The SM-alpha-actin protein expression in group C (0.219 +/- 0.018) was significantly lower than those in group A (0.319 +/- 0.011) and group B (0.325 +/- 0.005, all P < 0.01), but the protein expression in group E (0.328 +/- 0.016), group F (0.386 +/- 0.025), group G (0.442 +/- 0.017) and group H (0.501 +/- 0.018) was significantly higher than that in group C (all P < 0.01), while that in group F, group G and group H was significantly higher than those in group A and group B (all P < 0.01). The SM-alpha-actin mRNA expression in group C (0.144 +/- 0.009) was significantly lower than those in group A (0.299 +/- 0.023) and group B (0.296 +/- 0.041, all P < 0.01), but the mRNA expression in group D (0.487 +/- 0.014), group E (0.501 +/- 0.020), group F (0.611 +/- 0.018), group G (0.774 +/- 0.013) and group H (0.851 +/- 0.026) was significantly higher than those in group A, group B and group C (all P < 0.01). CONCLUSION: atRA increased JWA gene expression in human pulmonary artery smooth muscle cells, and meanwhile, the cells differentiated into a contractive phenotype and the cell migration decreased.

Cell Movement↗
PubMed2005

Two human orthologues of Eco1/Ctf7 acetyltransferases are both required for proper sister-chromatid cohesion.

Genetic studies in yeast and Drosophila have uncovered a conserved acetyltransferase involved in sister-chromatid cohesion. Here, we described the two human orthologues, previously named EFO1/ESCO1 and EFO2/ESCO2. Similar to their yeast (Eco1/Ctf7 and Eso1) and fly (deco) counterparts, both proteins feature a conserved C-terminal domain consisting of a H2C2 zinc finger motif and an acetyltransferase domain that is able to catalyze autoacetylation reaction in vitro. However, no similarity can be detected outside of the conserved domain. RNA interference depletion experiment revealed that EFO1/ESCO1 and EFO2/ESCO2 were not redundant and that both were required for proper sister-chromatid cohesion. The difference between EFO1 and EFO2 also is reflected in their cell cycle regulation. In mitosis, EFO1 is phosphorylated, whereas EFO2 is degraded. Furthermore, both proteins associate with chromosomes, and the chromosome binding depends on the diverse N-terminal domains. We propose that EFO1 and EFO2 are targeted to different chromosome structures to help establish or maintain sister-chromatid cohesion.

Acetyltransferases↗
PubMed2005

[Clinical observation of the lead discharging effect of paiqian chewing tablet].

OBJECTIVE: To observe the effect of paiqian chewing tablet (PQCT) on lead discharging and health in children. METHODS: Adopting self-control and inter-group control method, 94 children with blood lead level exceeding 100 microg/L were randomly divided into the observed group and the control group. The observation period for both groups was 30 days. RESULTS: At the 20th and 30th day of treatment, the urinary lead output in the observed group was significantly higher than that in the control group (P < 0.05, P < 0.01), and showed significant difference as compared with that before treatment (P < 0.05). Besides, the total amount of urinary lead discharging in the observed group was significantly more than that in the control group (P < 0.05). CONCLUSION: PQCT has markedly lead discharging improvement action with no influence on urinary calcium and zinc excretion. As all the routine indexes of blood and urine ranged within the normal extent, it demonstrated that PQCT was harmless to the health of observed individual.

Child↗
PubMed2005

[Pulmonary vascular remodeling and protein kinase C-alpha expression in chronic smoke exposure and/or hypoxia rats].

OBJECTIVE: To investigate pulmonary vascular remodeling and protein kinase C-alpha (PKC-alpha) expression in chronic smoke exposure and/or hypoxia rats. METHODS: Fifty-six male Wistar rats were randomly divided into seven groups: control group (C group), smoke exposure groups (S(4W), S(8W) group), hypoxia groups (H(4W), H(8W) group), smoke exposure plus hypoxia groups (SH(4W), SH(8W) group). Wistar rats were exposed to cigarette smoke and/or hypoxia air [O2 (10.0 +/- 0.5)%] for 4 to 8 weeks. A method by right cardiac catheterization was used for measuring mean pulmonary artery pressure (mPAP). Right ventricle (RV), left ventricle (LV) plus interventricular septum (S) were split and weighed and right ventricular hypertrophy index (RVHI) was calculated. To evaluate vascular remodeling, alpha-smooth muscle actin (alpha-SM-actin) staining and count of the percentage of muscularized small pulmonary arteries which was determined by morphometric analysis of histological sections were used. Pulmonary artery smooth muscle cell (PASMC) apoptosis was detected by in situ end labeling technique (TUNEL), and proliferation by proliferating cell nuclear antigen (PCNA) staining. Reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence staining and Western blot analysis were used for the detection of PKC-alpha mRNA and protein expression in pulmonary arteries. RESULTS: mPAP in H(4W), H(8W), SH(4W), SH(8W) group [(31 +/- 7), (32 +/- 8), (32 +/- 9), (31 +/- 10) mm Hg, 1 mm Hg = 0.133 kPa] were higher than that in C group [(14 +/- 4) mm Hg, all P < 0.01], but mPAP in S(4W) and S(8W) group [(15 +/- 5), (16 +/- 6) mm Hg] were not increased (all P > 0.05). In S(4W), S(8W), H(4W), H(8W), SH(4W) and SH(8W) group, RVHI (0.258 +/- 0.024, 0.394 +/- 0.021, 0.374 +/- 0.020, 0.414 +/- 0.019, 0.434 +/- 0.023, 0.442 +/- 0.020, respectively), the percentage of muscularized arteries [(33.5 +/- 6.8)%, (41.1 +/- 9.8)%, (35.9 +/- 6.6)%, (46.0 +/- 6.3)%, (42.9 +/- 6.5)%, (50.2 +/- 9.9)%, respectively] and alpha-SM-actin expression (53 +/- 15, 75 +/- 14, 56 +/- 11, 82 +/- 17, 83 +/- 17, 98 +/- 16, respectively) were increased significantly (all P < 0.01). PASMC apoptosis was increased and proliferation was markedly increased. Apoptotic indices (AI, 2.5 +/- 1.0, 3.8 +/- 1.4, 2.3 +/- 1.1, 3.3 +/- 1.1, 3.5 +/- 1.4, 4.8 +/- 1.4, respectively) and proliferation indices (PI, 33.1 +/- 11.8, 43.8 +/- 11.0, 36.5 +/- 10.6, 46.3 +/- 12.1, 45.3 +/- 12.4, 53.3 +/- 13.4, respectively) were higher than those in C group (all P < 0.01). The expressions of PKC-alpha mRNA and protein were higher than those of C group (all P < 0.01). The differences were more significant between SH(4W) and H(4W) group, SH(8W) and H(8W) group (all P < 0.01). CONCLUSIONS: It is suggested that smoke is synergistic with hypoxia in aggravating pulmonary vascular remodeling. The possible mechanism is through PKC signaling transduction pathway activation.

Animals↗
PubMed2004

Human Bub1 protects centromeric sister-chromatid cohesion through Shugoshin during mitosis.

Sister chromatids in mammalian cells remain attached mostly at their centromeres at metaphase because of the loss of cohesion along chromosome arms in prophase. Here, we report that Bub1 retains centromeric cohesion in mitosis of human cells. Depletion of Bub1 or Shugoshin (Sgo1) in HeLa cells by RNA interference causes massive missegregation of sister chromatids that originates at centromeres. Surprisingly, loss of chromatid cohesion in Bub1 and Sgo1 RNA-interference cells does not appear to require the full activation of separase but, instead, triggers a mitotic arrest that depends on Mad2 and Aurora B. Bub1 maintains the steady-state levels and centromeric localization of Sgo1. Therefore, Bub1 protects centromeric cohesion through Shugoshin in mitosis.

Aurora Kinase B↗
PubMed2004

Imaging calcium entering the cytosol through a single opening of plasma membrane ion channels: SCCaFTs--fundamental calcium events.

Recently, it has become possible to record the localized fluorescence transient associated with the opening of a single plasma membrane Ca(2+) permeable ion channel using Ca(2+) indicators like fluo-3. These Single Channel Ca(2+) Fluorescence Transients (SCCaFTs) share some of the characteristics of such elementary events as Ca(2+) sparks and Ca(2+) puffs caused by Ca(2+) release from intracellular stores (due to the opening of ryanodine receptors and IP(3) receptors, respectively). In contrast to intracellular Ca(2+) release events, SCCaFTs can be observed while simultaneously recording the unitary channel currents using patch-clamp techniques to verify the channel openings. Imaging SCCaFTs provides a way to examine localized Ca(2+) handling in the vicinity of a channel with a known Ca(2+) influx, to obtain the Ca(2+) current passing through plasma membrane cation channels in near physiological solutions, to localize Ca(2+) permeable ion channels on the plasma membrane, and to estimate the Ca(2+) currents underlying those elementary events where the Ca(2+) currents cannot be recorded. Here we review studies of these fluorescence transients associated with caffeine-activated channels, L-type Ca(2+) channels, and stretch-activated channels. For the L-type Ca(2+) channel, SCCaFTs have been termed sparklets. In addition, we discuss how SCCaFTs have been used to estimate Ca(2+) currents using the rate of rise of the fluorescence transient as well as the signal mass associated with the total fluorescence increase.

Animals↗
PubMed2004

Using total fluorescence increase (signal mass) to determine the Ca2+ current underlying localized Ca2+ events.

The feasibility of determining localized Ca(2+) influx using only wide-field fluorescence images was explored by imaging (using fluo-3) single channel Ca(2+) fluorescence transients (SCCaFTs), due to Ca(2+) entry through single openings of Ca(2+)-permeable ion channels, while recording unitary channel currents. Since the image obtained with wide-field optics is an integration of both in-focus and out-of-focus light, the total fluorescence increase (DeltaF(total) or "signal mass") associated with a SCCaFT can be measured directly from the image by adding together the fluorescence increase due to Ca(2+) influx in all of the pixels. The assumptions necessary for obtaining the signal mass from confocal linescan images are not required. Two- and three-dimensional imaging was used to show that DeltaF(total) is essentially independent of the position of the channel with respect to the focal plane of the microscope. The relationship between Ca(2+) influx and DeltaF(total) was obtained using SCCaFTs from plasma membrane caffeine-activated cation channels when Ca(2+) was the only charge carrier of the inward current. This relationship was found to be linear, with the value of the slope (or converting factor) affected by the particular imaging system set-up, the experimental conditions, and the properties of the fluorescent indicator, including its binding capacity with respect to other cellular buffers. The converting factor was used to estimate the Ca(2+) current passing through caffeine-activated channels in near physiological saline and to estimate the endogenous buffer binding capacity. In addition, it allowed a more accurate estimate of the Ca(2+) current underlying Ca(2+) sparks resulting from Ca(2+) release from intracellular stores via ryanodine receptors in the same preparation.

Aniline Compounds↗
PubMed2004

Validation of a new pediatric air-displacement plethysmograph for assessing body composition in infants.

BACKGROUND: The accurate measurement of body composition is useful in assessments of infant growth and nutritional status. OBJECTIVE: This study evaluated the reliability and accuracy of a new air-displacement plethysmography (ADP) system for body-composition assessment in infants. DESIGN: Between- and within-day reliability was assessed by comparing the percentage body fat (%BF) obtained on consecutive days and on the same day, respectively, in 36 full-term infants. Accuracy was assessed by comparing %BF measured with the use of ADP and %BF measured with the use of deuterium (2H2O) dilution in 53 infants. RESULTS: There were no significant differences in %BF between days (-0.50 +/- 1.21%BF) or within days (0.16 +/- 1.44%BF). Mean between- and within-day test-retest SDs of 0.69 and 0.72%BF, respectively, indicated excellent reliability. The %BF measurements obtained by using ADP were not significantly influenced by infant behavioral state. Mean %BF obtained by using ADP (20.32%BF) did not differ significantly from that obtained by using 2H2O dilution (20.39%BF), and the regression line [%BF(2H2O) = 0.851%BF (ADP) + 3.094] gave a high R2 (0.76) and a low SEE (3.26). The 95% limits of agreement between ADP and 2H2O (-6.84%BF, 6.71%BF) were narrower than those reported for other body-composition techniques used in infants. Individual differences between the 2 methods were not a function of body mass or fatness. CONCLUSION: ADP is a reliable and accurate instrument for determining %BF in infants, and it has the potential for use in both research and clinical settings.

Body Composition↗
PubMed2003

Synthesis, characterization, DNA-binding and cleavage studies of [Ru(bpy)2(actatp)]2+ and [Ru(phen)2(actatp)]2+ (actatp=acenaphthereno[1,2-b]-1,4,8,9-tetraazariphenylence).

New ligand acenaphthereno[1,2-b]-1,4,8,9-tetraazariphenylence (actatp) and its complexes [Ru(bpy)(2)(actatp)](ClO(4))(2).2H(2)O (1) (bpy=2,2'-bipyridine) and [Ru(phen)(2)(actatp)](ClO(4))(2).2H(2)O (2) (phen=1,10-phenanthroline) have been synthesized and characterized by UV-vis, 1H NMR, and mass spectra. The electrochemical behavior of the two complexes was studied by cyclic voltammetry. The interaction of the two complexes with calf thymus DNA has been investigated by spectrophotometric methods and viscosity measurements. The experimental results suggest that both complexes bind to DNA through an intercalative mode. The circular dichroism signals of the dialysates of the racemic complexes against calf thymus DNA are discussed. When irradiated at 302 nm, both complexes have also been found to promote the photocleavage of plasmid pBR 322 DNA.

2,2'-Dipyridyl↗
PubMed2002

Anaphase specific auto-cleavage of separase.

Sister-chromatid separation is triggered by a specific proteolytic cleavage of chromosomal cohesins catalyzed by the endopeptidase separase. Prior to anaphase, separase is inhibited independently by affinity binding to securin and by specific inhibitory phosphorylation. Here we show that separase itself is also subjected to proteolytic cleavages at three adjacent sites. The cleavages are auto-catalyzed and occur specifically at anaphase coincident with separase activation. The cleaved fragments remain associated with each other and are catalytically active. Mapping of the cleavage sites reveals that all three sites are conserved in vertebrates underlining a significant function for this regulation.

Amino Acid Sequence↗
PubMed2002

Visualization of Ca2+ entry through single stretch-activated cation channels.

Stretch-activated channels (SACs) have been found in smooth muscle and are thought to be involved in myogenic responses. Although SACs have been shown to be Ca(2+) permeable when Ca(2+) is the only charge carrier, it has not been clearly demonstrated that significant Ca(2+) passes through SACs in physiological solutions. By imaging at high temporal and spatial resolution the single-channel Ca(2+) fluorescence transient (SCCaFT) arising from Ca(2+) entry through a single SAC opening, we provide direct evidence that significant Ca(2+) can indeed pass through SACs and increase the local [Ca(2+)]. Results were obtained under conditions where the only source of Ca(2+) was the physiological salt solution in the patch pipette containing 2 mM Ca(2+). Single smooth muscle cells were loaded with fluo-3 acetoxymethyl ester, and the fluorescence was recorded by using a wide-field digital imaging microscope while SAC currents were simultaneously recorded from cell-attached patches. Fluorescence increases at the cell-attached patch were clearly visualized before the simultaneous global Ca(2+) increase that occurred because of Ca(2+) influx through voltage-gated Ca(2+) channels when the membrane was depolarized by inward SAC current. From measurements of total fluorescence ("signal mass") we determined that about 18% of the SAC current is carried by Ca(2+) at membrane potentials more negative than the resting level. This would translate into at least a 0.35-pA unitary Ca(2+) current at the resting potential. Such Ca(2+) currents passing through SACs are sufficient to activate large-conductance Ca(2+)-activated K(+) channels and, as shown previously, to trigger Ca(2+) release from intracellular stores.

Animals↗