Biomedical subjects

Wen Deng

Publications and source records attributed to Wen Deng.

At least 19 recordsLinked to original sources

PubMed2026

Impact of oxidative stress on malignant tumor progression and emerging therapeutic strategies.

Oxidative stress, driven by an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, plays a pivotal role in cancer biology. While persistent, moderately elevated ROS levels can promote genomic instability, tumor progression, and immune evasion, excessive ROS accumulation can overwhelm antioxidant defenses and trigger cancer cell death. Despite promising preclinical findings, clinical translation remains a challenge because of the context-dependent effects of ROS. A deeper understanding of oxidative stress regulation may lead to the development of novel precision medicine strategies, optimizing cancer therapies while minimizing adverse effects. This review highlights the concentration-dependent effects of oxidative stress in tumorigenesis, focusing on its impact on DNA damage, metabolic reprogramming, and immune modulation. We discuss recent advancements in ROS-targeting strategies, including pro-oxidant therapies that exploit redox vulnerabilities in cancer cells and antioxidant-based approaches aimed at mitigating oxidative stress-driven resistance to treatment. Moreover, we examine the interplay between oxidative stress and the tumor microen-vironment, emphasizing its influence on immune surveillance and therapeutic responses. This re-view provides insights into ROS-targeting interventions and their potential in oncologic treatment paradigms.

malignant tumors↗

PubMed2026

Efficacy of NAs in combination with Peg-IFN for functional cure in patients with CHB: a meta-analysis of RCTs.

BACKGROUND: The goal of treating chronic hepatitis B (CHB) is to achieve functional cure. We aimed to evaluate the efficacy of the combination of nucleoside (acid) analogues (NAs) and pegylated interferon (Peg-IFN) on the functional cure of CHB patients at the EOT and at the EOF. METHOD: PubMed, Embase, and Web of Science were searched systematically up to March 15, 2025. Sixteen RCTs on CHB patients receiving combination or monotherapy were included. RESULT: Compared with NAs treatment, the NAs combined with Peg-IFN treatment group significantly improved HBsAg clearance rate (RR: 14.05, 95% CI 6.13-32.20) and HBsAg seroconversion rate (RR: 12.82, 95% CI 5.08-32.33) at the EOT. Moreover, compared with NAs treatment, the NAs combined with Peg-IFN treatment group significantly improved HBsAg clearance rate (RR: 7.70, 95% CI 4.24-13.98), HBsAg seroconversion rate (RR: 11.93, 95% CI 5.14-27.67) at the EOF. However, compared with Peg-IFN monotherapy, the combination therapy group did not show any improvement in HBsAg clearance rate, HBsAg seroconversion rate, and the rate of qHBsAg decrease > 1 log10 IU/mL at the EOT and the EOF. Moreover, in terms of safety, the Peg-IFN monotherapy group showed more ALT flares (ALT > 5 × ULN) during the treatment process. CONCLUSION: Compared with NAs therapy, Peg-IFN combined with NAs therapy significantly improves functional cure rate. However, combination therapy shows no additional advantage over Peg-IFN monotherapy in achieving functional cure. The Peg-IFN monotherapy group has a higher incidence of ALT flares than the combination therapy group.

Humans↗

PubMed2006

Inactivation of human MAD2B in nasopharyngeal carcinoma cells leads to chemosensitization to DNA-damaging agents.

Rev7p has been suggested to play an important role in regulating DNA damage response in yeast, and recently, the human homologue (i.e., MAD2B) has been identified, which shares significant homology to the mitotic checkpoint protein MAD2. In this study, we investigated whether MAD2B played a key role in cellular sensitivity to DNA-damaging anticancer drugs by suppressing its expression using RNA interference in nasopharyngeal carcinoma cells. Using colony formation assay, we found that suppression of MAD2B conferred hypersensitivity to a range of DNA-damaging agents, especially DNA cross-linkers, such as cisplatin, and gamma-irradiation. This effect was associated with reduced frequencies of spontaneous and drug-induced mutations, elevated phosphorylation of histone H2AX, and markedly increased chromosomal aberrations in response to DNA damage. In addition, there was also a significant decrease in cisplatin-induced sister chromatid exchange rate, a marker for homologous recombination-mediated post-replication repair in MAD2B-depleted cells. These results indicate that MAD2B may be a key factor in regulating cellular response to DNA damage in cancer cells. Our findings reveal a novel strategy for cancer therapy, in which cancer cells are sensitized to DNA-damaging anticancer drugs through inactivation of the MAD2B gene.

Cell Line, Tumor↗

PubMed2006

Co-overexpression of fibroblast growth factor 3 and epidermal growth factor receptor is correlated with the development of nonsmall cell lung carcinoma.

BACKGROUND: Lung cancer is a prevalent cancer with a poor prognosis. To develop a useful in vitro cell model, a cell line of lung squamous cell carcinoma (SCC-35) was established. METHODS: The SCC-35 cell was characterized by comparative genomic hybridization (CGH) and spectral karyotyping (SKY). Chromosome microdissection, fluorescence in situ hybridization (FISH), and Southern and Northern blots analyses were used to study target genes. RESULTS: Two amplicons were found at chromosomes 7p12 and 11q13. Amplification and overexpression of epidermal growth factor receptor (EGFR) at 7p12 and fibroblast growth factor 3 (FGF3) at 11q13 were found. To understand the correlation between these two genes in nonsmall cell lung carcinoma (NSCLC) more comprehensively, overexpression of FGF3 and EGFR was investigated by immunohistochemistry with a tissue microarray containing 406 NSCLC samples. Cytoplasmic overexpression of FGF3 and EGFR was detected in 61% and 69% NSCLC cases, respectively. More interestingly, a significant correlation between overexpression of FGF3 and EGFR was found in NSCLC. CONCLUSION: These results suggest that co-overexpression of FGF3 and EGFR may play an important role in the pathogenesis of lung carcinoma.

Carcinoma, Non-Small-Cell Lung↗

PubMed2005

Genomic instability in laminopathy-based premature aging.

Premature aging syndromes often result from mutations in nuclear proteins involved in the maintenance of genomic integrity. Lamin A is a major component of the nuclear lamina and nuclear skeleton. Truncation in lamin A causes Hutchinson-Gilford progerial syndrome (HGPS), a severe form of early-onset premature aging. Lack of functional Zmpste24, a metalloproteinase responsible for the maturation of prelamin A, also results in progeroid phenotypes in mice and humans. We found that Zmpste24-deficient mouse embryonic fibroblasts (MEFs) show increased DNA damage and chromosome aberrations and are more sensitive to DNA-damaging agents. Bone marrow cells isolated from Zmpste24-/- mice show increased aneuploidy and the mice are more sensitive to DNA-damaging agents. Recruitment of p53 binding protein 1 (53BP1) and Rad51 to sites of DNA lesion is impaired in Zmpste24-/- MEFs and in HGPS fibroblasts, resulting in delayed checkpoint response and defective DNA repair. Wild-type MEFs ectopically expressing unprocessible prelamin A show similar defects in checkpoint response and DNA repair. Our results indicate that unprocessed prelamin A and truncated lamin A act dominant negatively to perturb DNA damage response and repair, resulting in genomic instability which might contribute to laminopathy-based premature aging.

Aging, Premature↗

PubMed2005

Active kinase proteome screening reveals novel signal complexity in cardiomyopathy.

Recent advances in the characterization of the phosphoproteome have been limited to measuring phosphorylation statuses, which imply but do not measure protein kinase activity directly. As such, the ability to screen, compare, and define multiple protein enzymatic activities across divergent samples remains a daunting challenge in proteomics. Here, we describe a gel-based kinase assay coupled to MS identification as an approach to map global kinase activity and assign pathway architecture to specified biologic contexts. We demonstrate the utility of this method as a platform for the comparison of proteomes based on differences in both kinase activities and for use in the de novo substrate identification for individual kinases. This approach allowed us to map the signal perturbations in the post-natal heart that were associated with activation of a myopathic cascade as mediated by the mitogen-activated protein kinase MKK6 and established the novel observation that MKK6 promotes the development of cardiomyopathy through multiple substrate interactions.

Animals↗

PubMed2005

Immortalization of human extravillous cytotrophoblasts by human papilloma virus gene E6E7: sequential cytogenetic and molecular genetic characterization.

Extravillous cytotrophoblast (EVCT) cultures from the normal placentas of three pregnant women were transfected by HPVE6E7. Sequential cytogenetic and molecular analyses were performed to delineate genetic events that may be critical for cell immortalization. One line, PE1-E6E7, was immortalized successfully, whereas 2 other lines, PE3-E6E7 and PE4-E6E7, could not be maintained beyond crisis. Before crisis, the majority of cells in all lines were karyotypically normal. During the early stages of crisis, there was progressive telomere shortening. Most cells were karyotypically abnormal, with extreme cytogenetic divergence and a predominance of telomeric association and dicentric chromosomes affecting many chromosomes. At the later stages of crisis, the karyotype became more convergent with a drastic decrease in nonclonal aberrations. In PE1-E6E7, after crisis the karyotype was complex, with frequent centromeric rearrangements in the form of isochromosomes and whole-arm translocations. There were unbalanced structural aberrations and numerical changes, including loss of chromosome 13, that could be traced throughout the evolution of the line. These findings support the concept that immortalization is a relatively rare and nonrandom event that occurs only in cells that have acquired the necessary or critical genetic alterations. Telomeric dysfunction may be an important mechanism leading to the acquisition of complex karyotypical aberrations.

Cells, Cultured↗

PubMed2005

Establishment and characterization of a human first-trimester extravillous trophoblast cell line (TEV-1).

OBJECTIVE: Research into the biology of human trophoblast invasion has been hampered by a lack of in vitro models. The aim of this study was to establish and characterize a human extravillous trophoblast cell line from the first-trimester placenta. METHODS: Human papillomavirus type 16 (HPV16) E6/E7 genes were stably expressed in primary cultures of first-trimester placenta via a retroviral vector (pLXSN-E6/E7). Several clones were characterized for extravillous trophoblastic properties by reverse transcriptase polymerase chain reaction (RT-PCR), Western blotting, and immunocytochemistry. The activities of matrix metalloproteinase (MMP)-2 and MMP-9 were examined with gelatin zymography. One clone (TEV-1), which retains all the established criteria for extravillous trophoblasts, was used in microarray analysis with Stanford Human cDNA chip (41, 421 cDNA features) to examine the differential gene expression after treatment of transforming growth factor beta 1 (TGFbeta1). The responsive gene to TGFbeta1 treatment was confirmed by quantitative real-time PCR. RESULTS: The clonal TEV-1 has been passaged for more than 105 population doublings with no sign of senescence, the activation of telomerase at early passages, and a near-diploid karyotype. TEV-1 cells expressed cytokeratin 7, HLA-G (a histocompatibility antigen, class IB), and CD9 (the cluster of differentiation antigen 9), and secreted active MMP-2 and MMP-9. TGFbeta1 treatment altered the gene expression profile of TEV-1 cells with a marked up-regulation of insulin-like growth factor binding protein 3 (IGFBP3), which was confirmed by quantitative real-time PCR. In addition, the TEV-1 was nontumorigenic when injected into nude mice and unable to form colonies in soft agar. CONCLUSION: Phenotypic and biologic characteristics of TEV-1 were shown as the properties of extravillous trophoblasts; thus, the TEV-1 cell line may be used as a cell model in extravillous trophoblast studies.

Cell Line↗

PubMed2005

[Comparative genomic hybridization: the profile of chromosomal imbalances in esophageal squamous cell carcinoma].

OBJECTIVE: To characterize the profile of chromosomal imbalances of esophageal squamous cell carcinoma (SCC) in Linzhou, the high prevalence area of Henan province. METHODS: Comparative genomic hybridization (CGH) was used to examine 52 cases of primary SCC of esophagus. RESULTS: Gains in part or in whole of chromosome 3q, 8q, 5p, 1q, 6q, 18p, 20q and losses of 3p, 1p, 9q, 19p, 4p, 8p were detected frequently in SCC (> 20%). Gain of 3q, 5p, 1q, 11q13-14 and loss of 4pq, 13q were all significantly correlated with pathologic staging (P < 0.05). Gains of 8q, loss of 4p were linked to nodal metastasis (P < 0.05). Gains of 2p and loss of 4pq, 11q14-qter were associated with distant organ metastasis (P < 0.05). CONCLUSION: These observations suggest that 3q, 8q, 5p, 1q, 6q, 18p, and 20q may contain SCC-related oncogenes; 3p, 1p, 9q, 19p, 4p and 8p may contain SCC-related tumor suppressor genes. It is likely that gain of 3q, 5p, 1q, 11q13-14 and loss of 4pq, 13q are the genetic aberrations critical for the development of esophageal carcinoma, whereas gains of 8q, 2p and loss of 4pq, 11q14-qter are considered later events associated with tumor progression and are thought to confer metastatic potential to esophageal carcinoma. Furthermore, nodal and distant organ metastases involve different genes.

Carcinoma, Squamous Cell↗

PubMed2005

Establishment and characterization of a human non-small cell lung cancer cell line.

Lung cancer is one of the most common causes of cancer death worldwide. Although many efforts have been made to explore the mechanisms involved in the development of lung cancer, the genetic events involved in the pathogenesis of lung cancer are still unclear. For a better mechanistic scope of study, a well-established cellular model is essential. We report the establishment of a squamous cell carcinoma (SCC) cell line of human lung, SCC-37. Chromosomal abnormalities and global genomic alterations of SCC-37 were studied by spectral karyotyping (SKY) and comparative genomic hybridization (CGH), respectively. Results showed that SCC-37 was a hypodiploid with complex chromosomal rearrangements. Some of the alterations, such as the gain of 1q25-qter in SCC-37, have been correlated to the tumor recurrence of non-small cell lung cancer (NSCLC). Other interesting findings include the amplification of 3q25-qter and 12q13, suggesting the existence of important oncogenes in the amplicons. This cell line may thus provide a useful cellular resource for studying the pathogenesis of SCC of the lung in the future.

Aged↗

PubMed2005

[Genomic changes in primary lesion and lymph node metastases of esophageal squamous cell carcinoma].

BACKGROUND & OBJECTIVE: Local lymph node and blood metastasis could occur at early stage of esophageal squamous cell carcinoma (ESCC), which may be the key factors of its recurrence and poor prognosis. However, the mechanism of ESCC metastasis is unclear. This study was to analyze the genetic changes in primary lesion and lymph node metastases of ESCC, to screen for and locate ESCC metastasis-related genes. METHODS: Genomic alterations in 15 pairs of primary lesions and matched metastatic lymph nodes of ESCC were analyzed by comparative genomic hybridization (CGH). RESULTS: In the 15 pairs of tissues, the most common chromosomal alterations were the gains of 3q, 8q, 6p, 20p, 5p, 18p, 2p, 2q and 1q, and the losses of 10p, 10q, 17p, 18q, 4p and 13q. Of these changes, the most significant finding was the gain of 6p with a frequency of 47% in metastatic lymph nodes and 13% in primary lesions, and the gain of 20p with a frequency of 73% in metastatic lymph nodes and 33% in primary lesions. The second interesting finding was the loss of 10p with a frequency of 53% in metastatic lymph nodes and 13% in primary lesions, and the loss of 10q with a frequency of 47% in metastatic lymph nodes and 13% in primary lesions. CONCLUSION: The gains of 6p and 20p and the losses of 10p and 10q are common genomic alterations in primary lesion and lymph node metastases of ESCC, which may code ESCC metastasis-related genes.

Adult↗

PubMed2005

[Management of heart failure and timing of delivery in pregnancy].

OBJECTIVE: To explore the management of heart failure, the timing of delivery in pregnancy, and the influence on pregnant prognosis. METHODS: We retrospectively analyzed the incidence of heart failure, treatment results, pattern of termination, and time of termination in 356 cases of pregnancy with heart disease. RESULTS: One hundred and thirty-six (38.20%) cases were diagnosed as heart failure and 76 (55.88%) were moderate or severe heart failure. Heart failure tends to occur more easily in rheumatic heart diseases than in congenital heart diseases. Heart failure occurred more frequently in pregnancy with rheumatic heart diseases without the heart operation before pregnancy than that of pregnancy with congenital heart diseases. The occurence of the moderate and severe heart failure in pregnancy decreased in rheumatic heart diseases with surgical therapies compared with those without surgical therapies (P <0.05). Compared with pregnancy with heart failure controlled inadequately, pregnancy with effectively controlled heart failure had better tolerance during delivery and through the pregnancy, and puerperium. CONCLUSION: Congenital heart diseases and rheumatic heart diseases are the chief causes of heart failure during the gestation. Therapy before pregnancy, especially surgery to the rheumatic heart diseases, may improve the cardiac function during pregnancy. Monitoring heart function and selecting the proper timing to terminate pregnancy after controlling the heart failure in late pregnant period will be helpful to improve the prognosis of pregnant and perineonate.

Adult↗

PubMed2004

Distinct profiles of critically short telomeres are a key determinant of different chromosome aberrations in immortalized human cells: whole-genome evidence from multiple cell lines.

Chromosomal aberrations are common in cancers. However, the search for chromosomal aberrations leading to development of specific solid tumors has been severely hindered because the majority of solid tumors have complex chromosomal aberrations that differ within the same tumor types. A similar phenomenon exists in immortalized cell lines. The underlying mechanisms driving these diverse aberrations are largely unknown. Telomeres play crucial roles in protecting the integrity of eucaryotic chromosomes and maintaining genomic stability of human cells. Telomere lengths on individual chromosomes in normal human somatic cells are heterogeneous and undergo progressive shortening with aging process. In this study, for the first time, a molecular cytogenetic method using sequential telomere quantitative fluorescence in situ hybridization and spectral karyotyping on the same human metaphases was applied successfully to examine the dynamic profiles of individual telomere shortening and their relationship to chromosome aberrations in multiple human cell lines undergoing immortalization. Human ovarian surface epithelial cells and esophageal epithelial cells were immortalized by the expression of HPV16 E6 and E7, which drive cells to proliferate by inactivating p53 and Rb genes. In these cell lines, we consistently detected large-scale differences in telomere signal intensities not only among nonhomologous chromosome arms but also between some homologous chromosome arms. The cell lines derived from different donors had different profiles of critically short telomeres (lacking telomere signals). Strikingly, the different profiles of chromosomal structural aberrations in multiple immortalized cell lines were highly significantly associated with the distinct distributions of critically short telomeres in whole-genome. Since cellular immortalization is one of the hallmarks of cancer, our findings suggest that distinct profiles of critically short telomeres in different human individuals might play an essential role in determining the complex and individual-specific chromosomal structural aberrations in human solid tumors.

Cell Line, Transformed↗

PubMed2004

Single-molecule approach to bacterial genomic comparisons via optical mapping.

Modern comparative genomics has been established, in part, by the sequencing and annotation of a broad range of microbial species. To gain further insights, new sequencing efforts are now dealing with the variety of strains or isolates that gives a species definition and range; however, this number vastly outstrips our ability to sequence them. Given the availability of a large number of microbial species, new whole genome approaches must be developed to fully leverage this information at the level of strain diversity that maximize discovery. Here, we describe how optical mapping, a single-molecule system, was used to identify and annotate chromosomal alterations between bacterial strains represented by several species. Since whole-genome optical maps are ordered restriction maps, sequenced strains of Shigella flexneri serotype 2a (2457T and 301), Yersinia pestis (CO 92 and KIM), and Escherichia coli were aligned as maps to identify regions of homology and to further characterize them as possible insertions, deletions, inversions, or translocations. Importantly, an unsequenced Shigella flexneri strain (serotype Y strain AMC[328Y]) was optically mapped and aligned with two sequenced ones to reveal one novel locus implicated in serotype conversion and several other loci containing insertion sequence elements or phage-related gene insertions. Our results suggest that genomic rearrangements and chromosomal breakpoints are readily identified and annotated against a prototypic sequenced strain by using the tools of optical mapping.

Escherichia coli K12↗

PubMed2003

A new method for improving metaphase chromosome spreading.

BACKGROUND: The success of complex molecular cytogenetic studies depends on having properly spread chromosomes. However, inconsistency of optimum chromosome spreading remains a major problem in cytogenetic studies. METHODS: The metaphase spreading process was carefully timed to identify the most critical phase of chromosome spreading. The effects of dropping height of cell suspension, slide condition, drying time, fixative ratio, and relative humidity on the quality of metaphase spreads were studied by quantitative examination of metaphase chromosome spreads. Normal and immortalized human epithelial ovarian cells, neuroblastoma cells, and normal lymphocytes were tested. RESULTS: Humidity over the slide was the most important variable affecting the quality of chromosome spreads. Consistent improvement in chromosome spreading (larger metaphase area, less chromosome overlaps, or lower frequencies of broken metaphases) was obtained for all cell types if dynamic cell rehydration, occurring as fixative absorbs moisture from air, was made to coincide with the prompt fixation of spread chromosomes to the slide. This was achieved by dropping cells on dry glass slides placed in a shallow metal tray and then quickly lowering the tray into a covered 50 degrees C water bath for slide drying. CONCLUSIONS: A new and simple method for improving metaphase chromosome spreading was developed based on our study on the characteristics of chromosome spreading.

Cell Line, Tumor↗

PubMed2003

Role of short telomeres in inducing preferential chromosomal aberrations in human ovarian surface epithelial cells: A combined telomere quantitative fluorescence in situ hybridization and whole-chromosome painting study.

It is well established that specific cancers and immortalized cells have nonrandom chromosome aberrations. However, little is understood about the underlying mechanism that initiates these aberrations in human cells. To examine whether human chromosomes with the shortest telomeres initiate the preferential chromosomal aberrations before cellular immortalization, we simultaneously applied telomere quantitative fluorescence in situ hybridization and specific whole-chromosome painting on chromosomes 1, 5, 8, 17, 19, and 20 in human ovarian surface epithelial (HOSE 6-3) cells expressing human papilloma viral oncogenes (HPV16 E6E7). The HPV16 E6E7-expressing cells, with extended in vitro life span and telomerase-negative status, were previously identified as having nonrandom chromosomal imbalances and high frequencies of dicentrics. Our analyses showed that among six pairs of targeted chromosomes, chromosomes 8 and 20 showed critically short telomeres with an undetectable telomere signal in more than 50% of cells analyzed. These chromosomes with the critically short telomeres were preferentially involved in various types of chromosomal aberrations including dicentrics, translocations, breaks, insertions, and losses or gains of chromosomal elements. Our findings suggest that nonrandom chromosome aberrations in HOSE cells occurring before cellular immortalization could be caused by the telomere length heterogeneity.

Cell Line↗

PubMed2003

Comparative genomics of Salmonella enterica serovar Typhi strains Ty2 and CT18.

We present the 4.8-Mb complete genome sequence of Salmonella enterica serovar Typhi strain Ty2, a human-specific pathogen causing typhoid fever. A comparison with the genome sequence of recently isolated S. enterica serovar Typhi strain CT18 showed that 29 of the 4,646 predicted genes in Ty2 are unique to this strain, while 84 genes are unique to CT18. Both genomes contain more than 200 pseudogenes; 9 of these genes in CT18 are intact in Ty2, while 11 intact CT18 genes are pseudogenes in Ty2. A half-genome interreplichore inversion in Ty2 relative to CT18 was confirmed. The two strains exhibit differences in prophages, insertion sequences, and island structures. While CT18 carries two plasmids, one conferring multiple drug resistance, Ty2 has no plasmids and is sensitive to antibiotics.

Adenosine Triphosphatases↗

PubMed2003

[Clinical analysis of intrahepatic cholestasis during pregnancy in 150 patients].

OBJECTIVE: To explore the effect of intrahepatic cholestasis of pregnancy (ICP) on the mother and fetus, and to assess the clinical value of nonstress test. METHODS: The symptoms, biochemical examinations, fetal monitoring, and pregnant outcomes of 150 patients with ICP were analyzed retrospectively in our hospital. RESULTS: There was no linear relation among serum cholanic acid, glutamic-pyruvic transaminase, total bilirubin, and gestational age when skin pruritus of pregnant women appeared, but there was positive correlation among the neonate status, meconium-stained amniotic fluid, and the onset time of pruritus. There was no correlation between the amount of postpartum hemorrhage and the newborn Apgar scores. No significant difference was found in perinatal prognosis The appearance of skin between normal and abnormal outcomes in the nonstress test. CONCLUSION: pruritus can be a sign of the state of ICP patients. To carefully monitor and comprehensively and continuously estimate the fetal state, and to terminate the pregnancy at proper time are very important to improve the prognosis of perinatal infants.

Adult↗