Biomedical subjects

Bo Hu

Publications and source records attributed to Bo Hu.

At least 19 recordsLinked to original sources

PubMed2026

EGFR-co-amplified lncRNA ELDR drives glioblastoma tumorigenicity by enhancing BMI1 activity.

BACKGROUND: In glioblastoma (GBM), epidermal growth factor receptor (EGFR) amplification, one of the most prevalent genetic alterations, often occurs on extrachromosomal DNAs (ecDNAs) that contain amplified oncogenes and regulatory elements, driving tumor progression. Despite the central oncogenic role of EGFR amplification, therapeutic strategies targeting EGFR have demonstrated limited clinical efficacy, suggesting that additional mechanisms may underlie EGFR-driven GBM malignancy and treatment resistance. Long non-coding RNAs (lncRNAs) are critical regulators in cancer; however, the roles of EGFR-associated lncRNAs-particularly those localized on ecDNA-in GBM tumorigenicity and therapeutic resistance remain poorly understood. METHODS: Transcriptomic and genomic analyses were performed to identify lncRNAs co-amplified with EGFR. Biochemical and molecular biological studies were carried out to reveal the mechanisms. In vivo xenograft models were used to evaluate the tumorigenicity and the therapeutic efficacy of combination treatment strategies. RESULTS: The lncRNA EGFR long non-coding downstream RNA (ELDR) was co-amplified with EGFR on ecDNA and chromosomes and was associated with poor prognosis in glioma. ELDR promoted GBM tumorigenicity through a BMI1-dependent epigenetic mechanism operating in parallel with canonical EGFR signaling. Mechanistically, ELDR interacted with purine-rich element-binding protein A (PURA), disrupted the inhibitory PURA-BMI1 interaction, and thereby enhanced the activity of BMI1, a core component of Polycomb repressive complex 1 (PRC1). Therapeutically, combining a BMI1 inhibitor or ELDR-targeting antisense oligonucleotides (ASOs) with an EGFR inhibitor erlotinib significantly enhanced antitumor efficacy in preclinical models of  EGFR  -amplified GBM with high ELDR expression. CONCLUSION: EGFR co-amplified ELDR promotes GBM tumorigenicity by enhancing BMI1 activity. Targeting the ELDR-BMI1 axis in combination with EGFR inhibition represents a promising therapeutic strategy for a subset of  EGFR  -amplified GBMs with high ELDR expression.

EGFR↗

PubMed2026

Causal Relationships Between Modifiable Risk Factors and Gastroesophageal Reflux Disease: A Two-Sample Mendelian Randomization Study.

INTRODUCTION: Gastroesophageal reflux disease (GERD) is a prevalent digestive disorder, yet the causal roles of modifiable risk factors remain unclear. This study aims to investigate the causal relationships between 28 modifiable risk factors (including obesity traits, mental health disorders, sleep traits, metabolic comorbidities, and serum parameters) and GERD using two-sample Mendelian randomization (MR). Gastroesophageal reflux disease (GERD). Our findings aim to inform targeted prevention and treatment strategies for GERD. METHODS: This study obtained data from extensive genome-wide association studies (GWAS). Pooled data associated with gastroesophageal reflux associations were obtained from the 23andMe Research team's research, which included a total of 129,080 cases of gastroesophageal reflux and 473,524 controls of European ancestry. We conducted a univariable Mendelian randomization (MR) analysis to ascertain whether genetic evidence of exposure demonstrated a statistically significant association with the risk of GERD. Subsequently, a multivariable MR analysis was carried out to estimate the independent effects of the exposures on GERD. RESULTS: Univariable MR analysis utilizing extensive GWAS data suggested that genetic factors such as BMI, Waist circumference, Arm fat mass (left and right), Leg fat mass (left and right), Attention Deficit and Hyperactivity Disorder (ADHD), Major Depressive Disorder (MDD), Schizophrenia, Negative emotions (including nervousness, anxiety, tension, or depression), Insomnia, Sleep apnea syndrome, Sleep duration, and Snoring, as well as Total cholesterol levels and Apolipoprotein B levels, are associated with the development of GERD. Multivariate Mendelian randomization of BMI and Negative emotion as correction factors showed that Waist circumference, Arm fat mass (left and right), Leg fat mass (left and right), ADHD, Insomnia, Sleep apnea syndrome, and Snoring were associated with an increased risk of GERD (p< 0.05). Conversely, longer sleep duration was associated with a reduced risk of GERD (p< 0.05). DISCUSSION: This MR study reveals novel causal mechanisms in GERD pathogenesis: (1) Peripheral adiposity (arm/leg fat mass) exerts independent effects beyond central obesity, indicating site-specific fat distribution significance; (2) ADHD emerges as a distinct psychiatric risk factor independent of mental disorders; (3) Sleep apnea operates through BMI-independent pathways. Collectively, these findings redefine GERD pathophysiology, highlighting fat depot specificity and brain-gut interactions as critical mechanistic drivers. CONCLUSION: Overall, our findings suggest that multiple risk factors are associated with the risk of GERD. These results provide a theoretical basis for controlling body weight and plasticity, improving sleep habits, and preventing and timely seeking medical attention to reduce the occurrence of psychiatric disorders, which will be important strategies to prevent and alleviate GERD.

Humans↗

PubMed2024

Development of SacB-based counterselection for efficient allelic exchange in Fusobacterium nucleatum.

Fusobacterium nucleatum, prevalent in the oral cavity, is significantly linked to overall human health. Our molecular comprehension of its role in oral biofilm formation and its interactions with the host under various pathological circumstances has seen considerable advancements in recent years, primarily due to the development of various genetic tools for DNA manipulation in this bacterium. Of these, counterselection-based unmarked in-frame mutation methods have proved notably effective. Under suitable growth conditions, cells carrying a counterselectable gene die, enabling efficient selection of rare, defined allelic exchange mutants. The sacB gene from Bacillus subtilis, encoding levansucrase, is a widely used counterselective marker partly due to the easy availability of sucrose. Yet, its potential application in F. nucleatum genetic study remains untested. We demonstrated that F. nucleatum cells expressing sacB in either a shuttle or suicide plasmid exhibit a lethal sensitivity to supplemental sucrose. Utilizing sucrose counterselection, we created an in-frame deletion of the F. nucleatum tonB gene, a critical gene for energy-dependent transport processes in Gram-negative bacteria, and a precise knock-in of the luciferase gene immediately following the stop codon of the hslO gene, the last gene of a five-gene operon possibly related to the natural competence of F. nucleatum. Post-counterselection with 5% sucrose, chromosomal plasmid loss occurred in all colonies, leading to gene alternations in half of the screened isolates. This sacB-based counterselection technique provides a reliable method for isolating unmarked gene mutations in wild-type F. nucleatum, enriching the toolkit for fusobacterial research.IMPORTANCEInvestigations into Fusobacterium nucleatum's role in related diseases significantly benefit from the strategies of creating unmarked gene mutations, which hinge on using a counterselective marker. Previously, the galk-based allelic exchange method, although effective, faced an inherent limitation-the need for a modified host. This study aims to surmount this limitation by substituting galK with sacB for gene modification in F. nucleatum. Our application of the sacB-based methodology successfully yielded a tonB in-frame deletion mutant and a luciferase gene knock-in at the precise chromosomal location in the wild-type background. The new method augments the existing toolkit for F. nucleatum research and has far-reaching implications due to the easy accessibility to the counterselection compound sucrose. We anticipate its broader adoption in further exploration, thereby reinforcing its critical role in propelling our understanding of F. nucleatum.

Fusobacterium nucleatum↗

PubMed2021

Dissecting spatial heterogeneity and the immune-evasion mechanism of CTCs by single-cell RNA-seq in hepatocellular carcinoma.

Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the transcriptome of 113 single CTCs from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) using single-cell full-length RNA sequencing in hepatocellular carcinoma (HCC) patients. We reveal that the transcriptional dynamics of CTCs were associated with stress response, cell cycle and immune-evasion signaling during hematogeneous transportation. Besides, we identify chemokine CCL5 as an important mediator for CTC immune evasion. Mechanistically, overexpression of CCL5 in CTCs is transcriptionally regulated by p38-MAX signaling, which recruites regulatory T cells (Tregs) to facilitate immune escape and metastatic seeding of CTCs. Collectively, our results reveal a previously unappreciated spatial heterogeneity and an immune-escape mechanism of CTC, which may aid in designing new anti-metastasis therapeutic strategies in HCC.

Aged↗

PubMed2007

Expression of VCA (viral capsid antigen) and EBNA1 (Epstein-Barr-virus-encoded nuclear antigen 1) genes of Epstein-Barr virus in Pichia pastoris and application of the products in a screening test for patients with nasopharyngeal carcinoma.

EBV (Epstein-Barr virus) serological tests have been used for many years as accessory diagnostic predictors of NPC (nasopharyngeal carcinoma). To date, IF (indirect immunofluorescence) assays still serve as the 'gold standard' for EBV serodiagnosis. However, IF assays are time-consuming, unsuitable for automatic handling and difficult to standardize. This makes their application in mass screening of populations inconvenient. Some of the technical difficulties associated with IF have been overcome by the development of specific ELISAs, but, at present, high sensitivity and specificity cannot be achieved simultaneously by using recombinant protein-based ELISAs, as the diagnostic value of different fragments of EBV in NPC is different. In an attempt to determine a suitable recombinant EBV protein for diagnostic purposes, fragments of EBV VCA (viral capsid antigen) and EBNA1 (Epstein-Barr-virus-encoded nuclear antigen 1) genes were expressed in the methylotrophic yeast Pichia pastoris, and a novel ELISA was established using P. pastoris-expressed VCA-BALF4 [aa (amino acids) 287-623; the BALF4 gene encodes the EBV glycoprotein gp125], EBNA1 (aa 390-641) and VCA-BFRF3 (the gene BFRF3 encodes a viral structural capsid protein or tegument protein VCA p18) proteins. Serum samples were collected from patients with NPC and healthy controls and were tested using this ELISA. The sensitivity of VCA-BFRF3, VCA-BALF4 and EBNA1 tests in the NPC sera were 65.0 (195/300), 76.3 (229/300) and 81.4% (244/300) respectively, whereas the specificity of normal individuals were 92 (460/500), 96 (480/500) and 95.8% (479/500). The optimum combination is VCA-BALF4 plus EBNA1, which identified 90.3% (271/300) of the NPC patients and had a specificity of 92.8% (464/500) for normal individuals. The results obtained from the evaluation of three antibodies to EBV as markers for detecting NPC suggests that a combination of EBNA1 (aa 390-641) and VCA-BALF4 (aa 287-623) assays would give better results in screening for NPC.

Adult↗

PubMed2006

Properties of R(2) statistics for logistic regression.

Various R(2) statistics have been proposed for logistic regression to quantify the extent to which the binary response can be predicted by a given logistic regression model and covariates. We study the asymptotic properties of three popular variance-based R(2) statistics. We find that two variance-based R(2) statistics, the sum of squares and the squared Pearson correlation, have identical asymptotic distribution whereas the third one, Gini's concentration measure, has a different asymptotic behaviour and may overstate the predictivity of the model and covariates when the model is mis-specified. Our result not only provides a theoretical basis for the findings in previous empirical and numerical work, but also leads to asymptotic confidence intervals. Statistical variability can then be taken into account when assessing the predictive value of a logistic regression model.

Biometry↗

PubMed2006

Efficient routing on complex networks.

We propose a routing strategy to improve the transportation efficiency on complex networks. Instead of using the routing strategy for shortest path, we give a generalized routing algorithm to find the so-called efficient path, which considers the possible congestion in the nodes along actual paths. Since the nodes with the largest degree are very susceptible to traffic congestion, an effective way to improve traffic and control congestion, as our strategy, can be redistributing traffic load in central nodes to other noncentral nodes. Simulation results indicate that the network capability in processing traffic is improved more than 10 times by optimizing the efficient path, which is in good agreement with the analysis.

Journal Article↗

PubMed2006

Mutual attraction model for both assortative and disassortative weighted networks.

For most complex networks, the connection between a pair of nodes is the result of their mutual affinity and attachment. In this letter, we will propose a mutual attraction model to characterize weighted evolving networks. By introducing the initial attractiveness A and the general mechanism of mutual attraction (controlled by parameter m), our model can naturally reproduce scale-free distributions of degree, weight, and strength, as found in many real systems. Also, simulation results are consistent with theoretical predictions. Interestingly, we obtain nontrivial clustering coefficient C and tunable degree assortativity r, depending on the values of m and A. Our model appears as a more general one that unifies the characterization of both assortative and disassortative weighted networks.

Journal Article↗

PubMed2006

Angiopoietin 2 induces glioma cell invasion by stimulating matrix metalloprotease 2 expression through the alphavbeta1 integrin and focal adhesion kinase signaling pathway.

Accumulating evidence reveals a significant correlation between angiopoietin 2 (Ang2) expression and tumor invasion and metastasis in various human cancers, but the major focus of recent studies has been on the angiogenic effects of Ang2. We recently reported that Ang2-stimulated glioma cell invasion results from the up-regulation and activation of matrix metalloprotease 2 (MMP-2) in tumor cells. In this study, we identify a novel mechanism by which Ang2 stimulates MMP-2 expression leading to glioma cell invasion. We show that Ang2 interacts with alpha(v)beta(1) integrin in Tie2-deficient human glioma cells, activating focal adhesion kinase (FAK), p130(Cas), extracellular signal-regulated protein kinase (ERK) 1/2, and c-jun NH(2)-terminal kinase (JNK) and substantially enhancing MMP-2 expression and secretion. The Ang2/alpha(v)beta(1) integrin signaling pathway was attenuated by functional inhibition of beta(1) and alpha(v) integrins, FAK, p130(Cas), ERK1/2, and JNK. Furthermore, expression of a negative regulator of FAK, FAK-related nonkinase, by U87MG/Ang2-expressing glioma xenografts suppressed Ang2-induced MMP-2 expression and glioma cell infiltration in the murine brain. These data establish a functional link between Ang2 interaction with alpha(v)beta(1) integrin and glioma cell invasion through the FAK/p130(Cas)/ERK1/2 and JNK-mediated signaling pathway.

Angiopoietin-2↗

PubMed2006

Estradiol and nicotine exposure enhances A549 bronchioloalveolar carcinoma xenograft growth in mice through the stimulation of angiogenesis.

Angiogenesis is required for lung cancer growth, which is mediated by various growth factors such as vascular endothelial growth factor (VEGF). Increases in VEGF and angiogenesis have been correlated with poor prognosis and survival in patients with lung cancer. In addition, recent reports show that estradiol and nicotine play important roles in lung tumor initiation and progression. In this report, we demonstrate that estradiol and nicotine exposure enhances the growth of A549 bronchioloalveolar carcinoma xenografts in mice through the stimulation of cell proliferation, VEGF secretion and angiogenesis. We detect a four-fold increase in microvascular density in tumors from mice exposed to estradiol and nicotine compared to control tumors resulting in an increase in tumor growth. Intriguingly, the effects on angiogenesis and tumor growth by the combination of agents were additive when compared to either agent alone. Furthermore, estradiol promotes VEGF secretion from various non-small cell lung carcinoma (NSCLC) cells and this effect is augmented by nicotine in a tumor xenograft model. These results indicate that aside from their roles in promoting cell proliferation, estradiol and nicotine appear to have additive effects on the induction of angiogenesis through the stimulation of VEGF secretion during NSCLC progression.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed2006

[Measurement on the atmospheric CO concentration in Beijing].

Carbon monoxide is considered as a criteria pollutant in urban areas, and plays an important role in photochemistry of regional and urban environments. Continuous measurement of CO at the meteorological observation tower in IAP-CAS (39 degrees 9'N, 116 degrees 4'E) from January to December 2004 was carried out in Beijing, using HP5890II gas chromatography (GC) with flame ionization detector(FID), at measurement frequency of 10 minutes. The diurnal variations of the atmospheric CO concentration at the urban area in Beijing show a very clear cycle with two peaks, one appears about 07:00 to approximately 08:00 in the morning and the other is at 22:00 to approximately 23:00 in the evening, with the maximum of 13.8mg x m(-3), 17.1 mg x m(-3), respectively. However, diurnal variations in four seasons are not very same. The variation range is bigger in winter and autumn seasons than that in summer and spring seasons. The concentration in fall and winter seasons dropped more quickly than that in spring and summer seasons after 07:00 to approximately 08:00. CO concentration diurnal variations are believed to be due to the combination results of surface emission sources and meteorological factors. The results indicate that there is an obviously seasonal cycle of CO concentration, with the maximum in Dec (4.0 +/- 3.4)mg x m(-3) and minimum in May (1.7 +/- 0.7)mg x m(-3). The average concentration of CO during the whole year is (2.6 +/- 1.9) mg x m(-3). The average concentration of CO during the heating period is (3.5 +/- 2.6)mg x m(-3), and (2.2 +/- 1.2) mg x m(-3) during the period without heating.

Air↗

PubMed2006

[Water-soluble chloride in aerosol PM10 in Beijing].

Water-soluble chloride is one of the most important components in aerosols. The chloride in PM10 measured from January to December 2004 in Beijing was determined using a system by combing rapid collection of fine particles and ion chromatography (RCFP-IC). The results showed that the annual average concentration of water-soluble chloride at the urban area in Beijing was about (3.1 +/- 1.7) microg x m(-3); the average concentration of chloride during the heating period was (4.6 +/- 2.1) microg m(-3) while it was (2.6 +/- 1.6) microg x m(-3) during the period no heating. The lowest concentration of (1.3 +/- 0.8) microg x m(-3) appeared in May, and the highest concentration appeared of (5.8 +/- 5.3) microg x m(-3) in December. Trends of the diurnal variation of water-soluble chloride depended on seasons. In autumn and winter, the higher concentration appeared in the daytime and the lower concentration appeared at night. In spring and summer, the higher concentration appeared at forenoon and the lower appeared at afternoon. Overall, the concentration of chloride in autumn and winter was higher than in spring and summer.

Aerosols↗

PubMed2006

[Simultaneous expression of modified hepatitis B surface antigen fusion polypeptides containing preS1, preS2 epitopes in Pichia pastoris].

At present time, the widely used hepatitis B virus( HBV) vaccines consist of only the small hepatitis B surface antigen expressed in yeast or CHO cells. The frequency of non-responders to these vaccines has increased the demand for a more immunogenic vaccine. Some studies have suggested that the addition of preS region to the vaccine will improve its efficacy. However, the large protein (L) containing the whole preS region can not be effectively expressed in vitro. To overcome this problem, two chimeric contructs, SS1, surface gene containing preS1 region at C-terminus and SS2, surface gene containing preS2 region at C-terminus, were constructed and effectively expressed in our previous studies. Here we further constructed an expression vector containing both SS1 and SS2 expression cassettes by separation and ligation the SS2 cassette to a linearized SS1 expression vector pAO815-SS1. The recombinant vector was transformed into Pichia pastoris GS115 by electroporation. A high-level expression strain (GS115-SS1S2) was established by primary screening for His+ transformants and further analysis for induction products. ELISA results demonstrated that the expressed protein had S, preS1 and preS2 antigenicities simultaneously. Western blotting showed that the product can bind to all of the three antibodies, anti-S, anti-preS1 and anti-preS2. The expression protein was present in the form of particles of 20-35 nm diameter and the yield of recombinant particles reached 300-600 mg/L by fermentation. The SS1 and SS2 polypeptides kept intact in purified particles, suggesting that the stability of preS region has been significantly improved.

Animals↗

PubMed2006

Stimulation of nisin production from whey by a mixed culture of Lactococcus lactis and Saccharomyces cerevisiae.

The production of nisin, a natural food preservative, by Lactococcus lactis subsp. lactis (ATCC 11454) is associated with the simultaneous formation of lactic acid during fermentation in a whey-based medium. As a result of the low concentration and high separation cost of lactic acid, recovering lactic acid as a product may not be economical, but its removal from the fermentation broth is important because the accumulation of lactic acid inhibits nisin biosynthesis. In this study, lactic acid removal was accomplished by biological means. A mixed culture of L. lactis and Saccharomyces cerevisiae was established in order to stimulate the production of nisin via the in situ consumption of lactic acid by the yeast strain, which is capable of utilizing lactic acid as carbon source. The S. cerevisiae in the mixed culture did not compete with the nisin-producing bacteria because the yeast does not utilize lactose, the major carbohydrate in whey for bacterial growth and nisin production. The results showed that lactic acid produced by the bacteria was almost totally utilized by the yeast and the pH of the mixed culture could be maintained at around 6.0. Nisin production by the mixed culture system reached 150.3 mg/L, which was 0.85 times higher than that by a pure culture of L. lactis.

Animals↗

PubMed2006

[Randomized controlled trials of acupuncture at Tiaokou (ST 38) for treatment of periarthritis of shoulder].

OBJECTIVE: To study the basic therapeutic function of Tiaokou (ST 38). METHODS: According to clinically multi-central randomized controlled and single-blind test principle, 257 cases of periarthritis of shoulder were divided into two groups, a test group (n = 124) treated with oral anti-inflammatory analgesic medicine combined with acupuncture at Tiaokou (ST 38), and a control group (n = 133) treated with oral anti-inflammatory analgesic medicine. Their therapeutic effects were compared. RESULTS: The total effective rate for stopping pain was 96.0% in the test group and 91.7% in the control group with a very significant difference between the two groups (P< 0.01). And the total effective rate for improvement of shoulder activity was 86.3% in the test group and 59.4% in the control group with a very significant difference between the two groups (P<0.01). CONCLUSION: Oral anti-inflammatory analgesic medicine combined with acupuncture has obvious therapeutic effect on periarthritis of shoulder, which is better than that of simple oral anti-inflammatory analgesic medicine.

Humans↗

PubMed2005

Catalpol prevents the loss of CA1 hippocampal neurons and reduces working errors in gerbils after ischemia-reperfusion injury.

Catalpol, an iridoid glycoside, contained richly in the roots of Rehmannia glutinosa, was found for the first time to be of neuroprotection in gerbils subjected to transient global cerebral ischemia. Catalpol (1 mg/kg ip) used immediately after reperfusion and repeatedly at 12, 24, 48 and 72 h significantly rescued neurons in hippocampal CA1 subfield and reduced working errors during behavioral testing. The neuroprotective efficacy of catalpol became more evident when the doses of catalpol were increased to 5 and 10mg/kg. In addition, it was exciting that the significant neuroprotection by catalpol was also evident when catalpol was applied up to 3 h after ischemia. But the neuroprotective efficacy of catalpol became weak when catalpol was given at 6h after ischemia. Of great encouragement was the finding that the neuroprotection of catalpol could be seen not only in a short post-ischemic period (12 days) but also in a long period (35 days). All these indicated that catalpol was truly neuroprotective rather than simply delayed the onset of neuronal damage and might be of therapeutic value for the treatment of global cerebral ischemia.

Analysis of Variance↗

PubMed2005

Mutual selection model for weighted networks.

For most networks, the connection between two nodes is the result of their mutual affinity and attachment. In this paper, we propose a mutual selection model to characterize the weighted networks. By introducing a general mechanism of mutual selection, the model can produce power-law distributions of degree, weight, and strength, as confirmed in many real networks. Moreover, we also obtained the nontrivial clustering coefficient C, degree assortativity coefficient r, and degree-strength correlation depending on a single parameter m. These results are supported by present empirical evidence. Studying the degree-dependent average clustering coefficient C(k) and the degree-dependent average nearest neighbors' degree k(nn)(k) also provide us with a better description of the hierarchies and organizational architecture of weighted networks.

Journal Article↗

PubMed2005

General dynamics of topology and traffic on weighted technological networks.

For most technical networks, the interplay of dynamics, traffic, and topology is assumed crucial to their evolution. In this Letter, we propose a traffic-driven evolution model of weighted technological networks. By introducing a general strength-coupling mechanism under which the traffic and topology mutually interact, the model gives power-law distributions of degree, weight, and strength, as confirmed in many real networks. Particularly, depending on a parameter W that controls the total weight growth of the system, the nontrivial clustering coefficient C, degree assortativity coefficient r, and degree-strength correlation are all consistent with empirical evidence.

Journal Article↗