Biomedical subjects

Li Bao

Publications and source records attributed to Li Bao.

16 recordsLinked to original sources

PubMed2026

Third-generation whole-genome sequencing reveals the role of CNTNAP2 as a tumor suppressor gene in high-risk neuroblastomas.

BACKGROUND: Neuroblastoma is a common and aggressive pediatric sympathetic nervous system tumor. Genomic structural variants (SVs) contribute substantially to neuroblastoma, yet remain under-characterized in high-risk neuroblastomas. We aimed to elucidate neuroblastoma pathogenesis using third-generation whole-genome sequence high-risk cases to identify driver aberrations and explore potential therapeutic strategies. METHODS: We analyzed third-generation whole-genome sequencing data of 20 high-risk neuroblastoma samples and combined the findings with those obtained from the analysis of clinical samples, in vitro models, and public datasets. RESULTS: The contactin-associated protein-like 2 (CNTNAP2) gene was observed to be frequently aberrated because of structural variants in high-risk neuroblastoma samples. CNTNAP2 expression was significantly correlated with favorable histology and could be used to predict prognosis using clinical samples and neuroblastoma datasets. Overexpression and knockdown experiments and transcriptomic analysis revealed that CNTNAP2 was primarily involved in neuronal differentiation and axon guidance pathways; moreover, CNTNAP2 was required for neuroblastoma differentiation and affected cancer stemness. Immunoprecipitation and mass spectrometry revealed that CNTNAP2 interacted with cytoskeletal proteins like drebrin 1 (DBN1) and myosin-heavy chain 9 (MYH9). CNTNAP2 dynamically reorganises actin and microtubules for DBN1-mediated neuronal differentiation. CNTNAP2 also reduces CTNNB1 transcription and β-catenin pathway activation by inhibiting MYH9 nuclear translocation. CNTNAP2 overexpression in neuroblastoma cell lines resulted in cell cycle arrest, decreased cell proliferation and metastasis. CONCLUSIONS: The recurrent loss of CNTNAP2 in neuroblastoma contributes to an aggressive phenotype by impairing neuronal differentiation and increasing cancer stemness. These findings may serve as a foundation for developing therapeutic strategies to overcome barriers to differentiation.

Humans↗

PubMed2024

Nanopore-based full-length transcriptome sequencing for understanding the underlying molecular mechanisms of rapid and slow progression of diabetes nephropathy.

BACKGROUND: Diabetic nephropathy (DN) has been a major factor in the outbreak of end-stage renal disease for decades. As the underlying mechanisms of DN development remains unclear, there is no ideal methods for the diagnosis and therapy. OBJECTIVE: We aimed to explore the key genes and pathways that affect the rate progression of DN. METHODS: Nanopore-based full-length transcriptome sequencing was performed with serum samples from DN patients with slow progression (DNSP, n = 5) and rapid progression (DNRP, n = 6). RESULTS: Here, transcriptome proclaimed 22,682 novel transcripts and obtained 45,808 simple sequence repeats, 1,815 transcription factors, 5,993 complete open reading frames, and 1,050 novel lncRNA from the novel transcripts. Moreover, a total of 341 differentially expressed transcripts (DETs) and 456 differentially expressed genes (DEGs) between the DNSP and DNRP groups were identified. Functional analyses showed that DETs mainly involved in ferroptosis-related pathways such as oxidative phosphorylation, iron ion binding, and mitophagy. Moreover, Functional analyses revealed that DEGs mainly involved in oxidative phosphorylation, lipid metabolism, ferroptosis, autophagy/mitophagy, apoptosis/necroptosis pathway. CONCLUSION: Collectively, our study provided a full-length transcriptome data source for the future DN research, and facilitate a deeper understanding of the molecular mechanisms underlying the differences in fast and slow progression of DN.

Humans↗

PubMed2007

H2O2 signaling in the nigrostriatal dopamine pathway via ATP-sensitive potassium channels: issues and answers.

The role of reactive oxygen species (ROS) as signaling agents is increasingly appreciated. Studies of ROS functions in the central nervous system, however, are only in their infancy. Using fast-scan cyclic voltammetry and fluorescence imaging in brain slices, the authors discovered that hydrogen peroxide (H2O2) is an endogenous regulator of dopamine release in the dorsal striatum. Given the key role of dopamine in motor, reward, and cognitive pathways, regulation by H2O2 has implications for normal dopamine function, as well as for dysfunction of dopamine transmission. In this review, data are summarized to show that H2O2 is a diffusible messenger in the striatum, generated downstream from glutamate receptor activation, and an intracellular signal in dopamine neurons of the substantia nigra, generated during normal pacemaker activity. The mechanism by which H2O2 inhibits dopamine release and dopamine cell activity is activation of ATP-sensitive K+ (KATP) channels. Characteristics of the neuronal and glial antioxidant networks required to permit H2O2 signaling, yet prevent oxidative damage, are also considered. Lastly, estimates of physiological H2O2 levels are discussed, and strengths and limitations of currently available methods for H2O2 detection, including fluorescence imaging using dichlorofluorescein (DCF) and the next generation of fluorescent probes, are considered.

Adenosine Triphosphate↗

PubMed2006

Pannexin 1 in erythrocytes: function without a gap.

ATP is a widely used extracellular signaling molecule. The mechanism of ATP release from cells is presently unresolved and may be either vesicular or channel-mediated. Erythrocytes release ATP in response to low oxygen or to shear stress. In the absence of vesicles, the release has to be through channels. Erythrocytes do not form gap junctions. Yet, here we show with immunohistochemical and electrophysiological data that erythrocytes express the gap junction protein pannexin 1. This protein, in addition to forming gap junction channels in paired oocytes, can also form a mechanosensitive and ATP-permeable channel in the nonjunctional plasma membrane. Consistent with a role of pannexin 1 as an ATP release channel, ATP release by erythrocytes was attenuated by the gap junction blocker carbenoxolone. Furthermore, under conditions of ATP release, erythrocytes took up fluorescent tracer molecules permeant to gap junction channels.

Adenosine Triphosphate↗

PubMed2005

Potent protection of ferulic acid against excitotoxic effects of maternal intragastric administration of monosodium glutamate at a late stage of pregnancy on developing mouse fetal brain.

The present study was conducted to investigate a possible protection of ferulic acid against excitotoxic effects of maternal intragastric (ig) administration of monosodium glutamate (MSG) at a late stage of pregnancy on developing mouse fetal brain. [(3)H]-labeled glutamate was used as radiotracer to study the effect of ferulic acid on distribution of MSG in mouse fetal brain. MSG dissolved in distilled water (2.0 g/kg body weight, 640 kBq of [(3)H]glutamate/mouse, ig) or/and sodium ferulate (SF) (20, 40, 80 mg/kg body weight, ip), was given to pregnant mice at 17-19 days; the distribution of [(3)H] glutamate in the mouse fetal brains was measured at 30, 60, 90, 120 min after administration of MSG or/and SF. Maternal mice were given MSG (1.0, 2.0, 4.0 g/kg body weight, ig) or/and SF (20, 40, 80 mg/kg body weight, ip) simultaneously at 17-19 days of pregnancy, and then behavioral tests and histopathological observations were used to analyze glutamate-induced functional and morphological changes of the brains of their offspring, and Western blot analysis was performed for examining expressions of bcl-2 and caspase-3. The results showed that SF obviously inhibited the uptake of labeled glutamate in fetal brain. In addition, SF countered the effects of MSG on behavior, histopathology, genetic toxicity, and expression of apoptosis-related gene. The results suggest that ferulic acid is a novel competitive N-methyl-D-aspartate (NMDA) receptor antagonist and neuroprotector. In conclusion, maternal administration of ferulic acid has potent protective effects against glutamate-induced neurotoxicity in their filial mice.

Animals↗

PubMed2005

Partial mitochondrial inhibition causes striatal dopamine release suppression and medium spiny neuron depolarization via H2O2 elevation, not ATP depletion.

Mitochondrial dysfunction is a potential causal factor in Parkinson's disease. We show here that acute exposure to the mitochondrial complex I inhibitor rotenone (30-100 nM; 30 min) causes concentration-dependent suppression of single-pulse evoked dopamine (DA) release monitored in real time with carbon-fiber microelectrodes in guinea pig striatal slices, with no effect on DA content. Suppression of DA release was prevented by the sulfonylurea glibenclamide, implicating ATP-sensitive K+ (KATP) channels; however, tissue ATP was unaltered. Because KATP channels can be activated by hydrogen peroxide (H2O2), as well as by low ATP, we examined the involvement of rotenone-enhanced H2O2 generation. Confirming an essential role for H2O2, the inhibition of DA release by rotenone was prevented by catalase, a peroxide-scavenging enzyme. Striatal H2O2 generation during rotenone exposure was examined in individual medium spiny neurons using fluorescence imaging with dichlorofluorescein (DCF). An increase in intracellular H2O2 levels followed a similar time course to that of DA release suppression and was accompanied by cell membrane depolarization, decreased input resistance, and increased excitability. Extracellular catalase markedly attenuated the increase in DCF fluorescence and prevented rotenone-induced effects on membrane properties; membrane changes were also largely prevented by flufenamic acid, a blocker of transient receptor potential (TRP) channels. Thus, partial mitochondrial inhibition can cause functional DA denervation via H2O2 and KATP channels, without DA or ATP depletion. Furthermore, amplified H2O2 levels and TRP channel activation in striatal spiny neurons indicate potential sources of damage in these cells. Overall, these novel factors could contribute to parkinsonian motor deficits and neuronal degeneration caused by mitochondrial dysfunction.

Adenosine Triphosphate↗

PubMed2005

[Treatment of refractory and relapsed acute lymphocytic leukemia in adults].

OBJECTIVE: To analyze on the efficacy and toxicity of fludarabine and teniposide + mitoxantrone (MIT) regimens on treating refractory and relapsed acute lymphocytic leukemia in adult patients. METHODS: Teniposide 100 mg/d, 5-7 d, MIT 10 mg/d, 2 d and fludarabine regimens [Flu 30 mg/(m(2) . d), 3- 5 d, Cytarabine (Ara-c )1-2 g/(m(2) . d), 5 d; Flu 50 mg/d, 5 d, Ara-c 200 mg/d, 5 d, MIT 4 mg/d, 4 d] were used to treat 42 cases of adults with refractory and relapsed acute lymphocytic leukemia(ALL). G-CSF 5 microg/(kg . d) were used when WBC<1.0 x 10(9)/L. RESULTS: In both the regimens fludarabine and VM (teniposide + MIT), the complete remission (CR) rate was 45% versus 31.8% (P>0.05); the median neutropenia began 6 days after the regimens arresting and lasting 10 versus 7.5 days, P>0.05; thrombocytopenia begin at time of 10 versus 6.5 days (P<0.05) after the regimens arresting and lasting 6 versus 10 days (P>0.05). Fludarabine regimen had less non-haematological toxic effect than that of VM. CONCLUSION: Compared with VM, Fludarabine regimen was a very effective alternative treatment for CR induction in adult patients with refractory and relapsed ALL and low toxicity.

Adolescent↗

PubMed2005

[Effect of ABO-incompatibility on allogeneic hematopoietic stem cell transplantation].

OBJECTIVE: To explore the effect of ABO mismatch on clinical characteristics in allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We retrospectively reviewed the clinical courses of 148 recipients of allo-HSCT from ABO-incompatible donors, of whom 85 ABO-compatible recipients were used as control group. RESULTS: In ABO major incompatible group, the time of erythrocyte recovery after bone marrow transplantation (BMT) was delayed and more RBC transfusions were required as compared with ABO major incompatible peripheral blood stem cell transplantation (PBSCT). The incidence of acute graft versus host disease (aGVHD), cytomegalovirus (CMV) infection and survival had no significant difference between ABO-incompatible and ABO-compatible recipients for BMT, PBSCT and BMT+PBSCT. CONCLUSION: ABO-incompatibility has no adverse effect on the outcome of HSCT. Allogeneic PBSCT can reduce red blood cell transfusion requirements and facilitate erythrocyte recovery as compared with BMT.

ABO Blood-Group System↗

PubMed2005

[Clinical study of Philadelphia chromosome-positive acute lymphoblastic leukemia].

OBJECTIVE: To study the clinical characteristics and therapeutic outcome of Ph+ acute lymphoblastic leukemia (ALL). METHODS: Thirty previously untreated cases of Ph+ B-ALL were diagnosed in our institute. The patients were treated with combination chemotherapy of CODP +/- L regimen, Imatinib (400 approximately 600 mg/d) was continuously given to those who couldn't reach CR. Fourteen patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CR, while 16 received consolidation of intensive chemotherapy. RESULTS: Thirty (32.6%) of 92 ALL patients were diagnosed as Ph+ ALL, with a median age of 25.5 (14 - 60). Among them Ph+ as the sole anomaly was seen in 16 patients, and Ph+ with additional chromosome abnormalities in 14. Besides the B cell markers, 23 (76.7%) patients had CD34+ and 13 (43.3%) CD13+ and/or CD33+. Nineteen of the Ph+ ALL patients underwent molecular analysis; 13 (68.4%) expressed P190 and 6 (31.6%) P210. Increased WBC (> 30 x 10(9)/L) was found in 22/30 cases while WBC > 100 x 10(9)/L in 9/30 cases. The chemotherapy complete remission rate was 68.8% in patients with only Ph+ versus 28.6% in those with additional chromosome abnormalities. All seven refractory/relapsed patients reached CR with Imatinib therapy. The total complete remission rate was 73.3% in all Ph+ ALL patients. The median remission duration was shorter in patients with additional chromosome than in those with only Ph+ (1 vs 7 months, P < 0.05), and so was the survival period (7 vs 9 months, P > 0.05). The remission duration was significantly longer in patients received allo-HSCT than in those received chemotherapy only (8 vs 0.5 month, P < 0.05), and so was the survival period (12.5 vs 6 months, P < 0.05). CONCLUSION: Additional chromosome abnormalities negatively affect the prognosis and therapeutic effect of Ph+ ALL patients. Imatinib is effective for the induction therapy of Ph+ ALL. The survival period of patients who received allo-HSCT was obviously longer than those who received chemotherapy only.

Adolescent↗

PubMed2005

[Pure red cell aplasia following major ABO-incompatible allogeneic hematopoietic stem cell transplantation].

OBJECTIVES: To study clinical characteristics and outcome of pure red cell aplasia (PRCA) following major ABO-incompatible allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Variables including sex, age, stem cell source, granulocyte engraftment time, blood transfusion and isoagglutinin type against donor RBC were analyzed to identify risk factors for the development of PRCA. RESULTS: Twelve of 100 patients received major ABO-incompatible allo-HSCT developed PRCA, with out any effect on incidence of aGVHD and CMV infection. ABO blood groups of recipient/donor pairs of these twelve PRCA patients were O/A in nine, B/A in one and O/B in two. Patients with anti-A isoagglutinins against donor RBC developed PRCA more frequently than those with anti-B (10/49 vs 2/49). Median duration to the recovery of erythropoiesis tended to be longer in patients with PRCA (PRCA vs non-PRCA, 203.5 vs. 76 days, P < 0.05 ). Median durations to the disappearance of incompatible isoagglutinins tended to be longer in patients with PRCA (PRCA vs. non-PRCA, 150.5 vs. 60 days,P <0.05) and in those with anti-A isoagglutinins (anti-A vs anti-B, 90 vs 55 days, P < 0.05). CONCLUSION: ABO blood group of O/A in recipient/donor pair was the only high risk factor for PRCA after major ABO-incompatible allo-HSCT.

ABO Blood-Group System↗

PubMed2004

Pannexin membrane channels are mechanosensitive conduits for ATP.

Intercellular calcium wave propagation initiated by mechanical stress is a phenomenon found in nearly all cell types. The waves utilize two pathways: transfer of InsP3 directly from cell to cell through gap junction channels and release of ATP onto extracellular purinergic receptors. The conduit for ATP has remained elusive and both a vesicular and a channel mediated release have been considered. Here, we describe the properties of single pannexin 1 channels. They have a wide expression spectrum, they are of large conductance and permeant for ATP, and they are mechanosensitive. Hence, pannexins are candidates for the release of ATP to the extracellular space upon mechanical stress.

Animals↗

PubMed2004

Connexins are mechanosensitive.

Connexins form gap junction channels that provide a hydrophilic path between cell interiors. Some connexins, particularly the lens connexins, Cx46 and Cx50 and their orthologs, can form functional hemichannels in nonjunctional membranes. These hemichannels are a nonselective conduit to the extracellular medium and may jeopardize cell survival. The physiological function of hemichannels has remained elusive, but it has been postulated that hemichannels are involved in ATP-release caused by mechanical stimulation. Here we show with single-channel and whole cell electrophysiological studies that Cx46 hemichannels are mechanosensitive, like other families of ion channels and membrane-bound enzymes. The hemichannel response to mechanical stress is bipolar. At negative potentials stress opens the channel, and at positive potentials stress closes it. Physiologically, Cx46 hemichannels may assist accommodation of the ocular lens by providing a transient path for volume flow as the lens changes shape.

Animals↗

PubMed2004

[Dynamic examination of the serum erythropoietin levels following ABO-incompatible allogeneic hematopoietic stem cell transplantation and its implications].

To evaluate the dynamic changes of erythropoietin (EPO) and its significance following ABO-incompatible allogeneic hematopoietic stem cell transplantation (allo-HSCT), sequential changes in serum EPO levels were measured by enzyme linked immunosorbent assay (ELISA) in 11 patients receiving allo-HSCT from ABO-incompatible donors. The results showed that the mean EPO level was markedly elevated and reached to its highest level at 0 day-2 week after allo-HSCT (233.73 +/- 81.95 mU/ml and 226.07 +/- 113.87 mU/ml respectively, P >0.05). Although the EPO levels were significantly lower at 1 month (128.49 +/- 108.92 mU/ml, P <0.05) and after the reversion of blood type (73.07 +/- 68.85 mU/ml, P <0.05), they were still elevated up to 2 months after allo-HSCT. The EPO levels always had significant positive correlation with the RBC transfusions. At 0 day and 4 week after allo-HSCT, the EPO levels had significant negative correlation with the Hb levels; at 6 and 8 week after allo-HSCT, the EPO levels had no relation with the Hb levels, they had significant positive correlation with the time of erythrocyte recovery and anti-A isoagglutinin titers at the same time. It is concluded that serum erythropoietin levels continuously increasing following ABO-incompatible allogeneic allo-HSCT suggest that exogenous recombinant human erythropoietin treatment for anemia may not be beneficial.

ABO Blood-Group System↗

PubMed2004

[Multiple factors in erythrocytic recovery following ABO-incompatible allogeneic HSCT].

This study was aimed to investigate various factors influening erythrocyte recovery following ABO-incompatible allogeneic HSCT. 157 patients following ABO-incompatible allogeneic HSCT were selected for the investigation. Cox regression analysis were used to identify the statistically significant factors including sex, age, schemes of transplantation, HLA-matched, mismathed, conditioning regimens, preventive measures for GVHD, occurrence of grade I-II GVHD, CMV infections and types of incompatible blood group. The results showed that minor ABO-incompatible, number of mononuclear cells infused, age of patients and unrelated BMT were four important main factors influening the erythrocyte recovery. In conclusion, the erythrocyte recovery is more quick in patients with minor ABO-incompatible and more number of mononuclear cells infused, while it is slow in patents with old age and unrelated BMT.

ABO Blood-Group System↗

PubMed2003

[Expression of cytidine deaminase mRNA in bone marrow cells from patients with acute leukemia].

The aim of the study was to determine the expression of cytidine deaminase (CDD) gene in bone marrow cells from patients with acute leukemia (AL) and evaluate the relationship between CDD expression and clinical feature. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was used for detection of expression level of CDD mRNA in bone marrow cells from 83 patients with acute leukemia and from 15 healthy peoples as control. CDD/beta-actin ratio >or= 0.5 was considered to be positive. The results showed that expression levels of CDD of 31 previously untreated patients were higher than those of 23 cases of AL in complete remission and of normal controls. Expression levels of CDD of 29 relapse/refractory patients were also higher than those of 23 AL patients in complete remission and of normal subjects. The expression levels of CDD in relapse/refractory ALL were higher than those in AML while expression levels of CDD were not correlated with the outcome of therapy. It is concluded that the level of CDD mRNA expression varies at the different stage of acute leukemia. The expression level of CDD seems not to be a prognostic factor.

Adolescent↗

PubMed2003

[Change of PML/PML-RARalpha protein during treatment with tetraarsenic tetrasulfide (As4S4) in patients with acute promyelocytic leukemia].

In order to explored the change of PML/PML-RARalpha protein during tetraarsenic tetrasulfide (As4S4) treatment, acute promyelocytic leukemia (APL) cells from a group of newly diagnosed APL patients were examined by indirect immunofluorescence staining with anit-PML monoclonal antibody. The results showed that all samples typically presented many microspeckle signals throughout the nucleus before treatment. The redistribution occurred as early as on the second day after As4S4 treatment, which revealed loss of microspeckles with the presentation of a few large speckles. Anti-PML staining also emerged in the perinuclear cytoplasm. At last, microspeckles and large speckles all disappeared. When the therapy was combining all-trans-retinoic acid (ATRA) with As4S4, similar results were obtained. However, APL cells from patients treated with ATRA alone performed totally different appearance, presenting microspeckles and large speckles at the same time, followed with entirely large speckles. The conclusion is that As4S4 makes redistribution of PML/PML-RARalpha protein in leukemic cells from APL patients during the treatment, which is quite different from that during the treatment of ATRA.

Adolescent↗