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Liang Chen

Publications and source records attributed to Liang Chen.

At least 19 recordsLinked to original sources

Antibacterial activity and mechanistic insights of Lucilia illustris antimicrobial peptide Cecropin A2 against Pseudomonas aeruginosa.

Pseudomonas aeruginosa (P. aeruginosa) poses a serious public health threat due to multidrug resistance and biofilm formation. This study investigated the antibacterial mechanisms of the antimicrobial peptide, Cecropin A2 (CA2), against P. aeruginosa. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CA2 against P. aeruginosa ATCC 9027 (PA ATCC 9027) were determined by broth microdilution. Antibacterial activity was evaluated using growth curves and time-kill assays. The mechanism was explored by assessing membrane integrity (outer/inner membrane permeability, SEM, and fluorescence microscopy), and intracellular responses (ATP, SDH activity, and ROS). Biofilm effects were assessed by crystal violet staining (biomass) and viable cell counting (biofilm-embedded bacteria). The MIC and MBC of CA2 against PA ATCC 9027 were 37.34 μM and 74.68 μM, respectively. CA2 exhibited moderate antibacterial activity against PA ATCC 9027. Scanning electron microscopy (SEM) revealed marked morphological damage after treatment. CA2 affected intracellular metabolism, potentially interacted with genomic DNA, and reduced biofilm biomass. Cecropin A2 exhibits concentration-dependent in vitro antibacterial activity against P. aeruginosa ATCC 9027, providing mechanistic insights and a theoretical basis for the development of alternative antimicrobial strategies.

Antimicrobial activity↗

Targeting PRMT9 overcomes venetoclax resistance in AML by modulating splicing and inhibiting translation.

Arginine methylation catalyzed by protein arginine methyltransferases (PRMTs) is required for cancer cell proliferation, but whether PRMTs mediate resistance to therapy remains unclear. Here, we performed loss-of-function screens in venetoclax-resistant (VEN-R) acute myeloid leukemia (AML) patient-derived xenograft cells and found that PRMT9 plays a critical role in promoting VEN resistance. Specifically, VEN-R AML samples exhibited high levels of PRMT9, and PRMT9 inhibition resensitized AML cells to VEN treatment. In preclinical resistant models, genetic ablation of PRMT9 synergized with VEN to eradicate AML cells. Consistently, pharmacologic inhibition of PRMT9 combined with VEN produced similar effects in VEN-R AML mouse models. Mechanistically, PRMT9 ablation disrupted RNA splicing by inducing exon skipping in mRNA encoding ALG13, an uridine diphosphate (UDP)-N-acetylglucosaminyltransferase subunit, thereby downregulating expression of the VEN efflux transporter encoded by the adenosine triphosphate-binding cassette subfamily C member 1 gene. PRMT9 inhibition also suppressed protein synthesis, leading to downregulation of short-lived oncoproteins such as MCL1. These findings establish a connection between PRMT9-mediated arginine methylation and poor VEN responsiveness and demonstrate that targeting PRMT9 may represent a viable strategy to overcome VEN resistance.

Protein-Arginine N-Methyltransferases↗

Genomic analysis of community-associated multidrug-resistant Klebsiella quasipneumoniae subsp. similipneumoniae and the identification of the ST2059-KL1 clone in the U.S.

UNLABELLED: Klebsiella quasipneumoniae subsp. similipneumoniae is an important member of the K. pneumoniae species complex (KpSC) and is increasingly reported as multidrug-resistant (MDR) in healthcare- and community-associated infections. Since clinical laboratories do not routinely distinguish K. quasipneumoniae subsp. similipneumoniae from K. pneumoniae, national prevalence estimates, particularly for MDR, are lacking. In this study, a total of 2,006 community-associated MDR KpSC isolates were collected from 42 U.S. states, with 30 K. quasipneumoniae subsp. similipneumoniae isolates originating from 12 states identified using whole genome sequencing. All isolates were resistant to ceftriaxone and exhibited high rates of resistance to other antimicrobial agents, including ampicillin-sulbactam (56.7%, 17/30), levofloxacin (75.9%, 22/29), and trimethoprim-sulfamethoxazole (53.3%, 16/30). Notably, five isolates were also carbapenem-resistant. Genomic analysis resolved 10 sequence types (STs), with ST2059 (n = 13) and ST414 (n = 9) predominating. Ceftriaxone resistance in most isolates (90%, 27/30) was conferred by an extended-spectrum β-lactamase gene, predominantly blaCTX-M-15 (73.3%, 22/30); the remaining isolates carried either a carbapenemase (blaKPC-3) or an AmpC β-lactamase (blaCMY-2). Nanopore sequencing identified blaCTX-M-15 harbored on two types of IncFIB(Kpn3) antimicrobial resistance (AMR) plasmids, either with or without the conjugative tra gene cluster. Interestingly, the KL1 locus, associated with canonical hypervirulent K. pneumoniae strains, was detected in all ST2059 isolates. Further analysis of public genomic data showed that the KL1 locus is widely distributed across KpSC. KL1 phylogenetic analyses indicated frequent intrasubspecies recombination but limited intersubspecies exchange of KL1. The identification of the dominant MDR K. quasipneumoniae subsp. similipneumoniae KL1-ST2059 clone in the U.S. underscores the importance of ongoing genomic surveillance. IMPORTANCE: Klebsiella quasipneumoniae subsp. similipneumoniae is an underrecognized member of the Klebsiella pneumoniae species complex that is frequently misidentified in clinical laboratories, leading to an incomplete understanding of its role in antimicrobial resistance. In this study, we used large-scale genomic surveillance of community-associated multidrug-resistant isolates across the U.S. to identify this subspecies as a reservoir of clinically relevant resistance plasmids. Notably, we detected a widely distributed ST2059 lineage carrying the K1 capsular locus, a feature traditionally associated with hypervirulent K. pneumoniae. These findings highlight the convergence of resistance and virulence-associated traits in an overlooked species and underscore the need for genomic surveillance to monitor emerging high-risk lineages in community settings.

Drug Resistance, Multiple, Bacterial↗

Choice of Anesthesia in Microelectrode Recording-guided Deep Brain Stimulation Surgery for Parkinson's Disease (CHAMPION): A Noninferiority Randomized Controlled Trial.

BACKGROUND: Deep brain stimulation for Parkinson's disease is often performed under conscious sedation or general anesthesia. However, anesthetic agents may influence intraoperative microelectrode recording, and the optimal anesthesia method for microelectrode recording remains unclear. This study compared general anesthesia and conscious sedation in preserving microelectrode recording signal intensity during deep brain stimulation. METHODS: In this prospective, noninferiority randomized controlled trial, patients with Parkinson's disease (United Kingdom Brain Bank criteria) undergoing elective bilateral surgery were randomized 1:1 to the conscious sedation or the general anesthesia group. During surgery, a desflurane anesthetic titrated against the quality of the electrophysiologic signal was applied in the general anesthesia group, whereas patients in the conscious sedation group received dexmedetomidine anesthesia. The primary outcome was the proportion of patients with high-quality microelectrode recording (normalized root mean square greater than 2.0), assessed postoperatively off-line. Secondary outcomes included operation and recording duration, 6-month clinical efficacy, and complication rates. RESULTS: Of 188 randomized patients (94 general anesthesia, 93 conscious sedation), desflurane anesthesia was noninferior for high normalized root mean square proportion (89.4% vs . 90.3%; difference, -0.96%; 95% CI, -9.62 to 7.70). The general anesthesia group had shorter operative time (difference, -9.07&#x2009;min; 95% CI, -13.99 to -4.14; P < 0.001). At 6 months, changes in Unified Parkinson's Disease Rating Scale score (difference, -2.50; 95% CI, -7.20 to 2.20; P = 0.297), levodopa equivalent daily dose (difference, -58.4&#x2009;mg; 95% CI, -133.56 to 16.75; P = 0.128), and complication rates (general anesthesia: 10.9% vs . conscious sedation: 8.9%; P = 0.655) were comparable between the groups. CONCLUSIONS: General anesthesia is noninferior to conscious sedation for microelectrode-guided subthalamic nucleus deep brain stimulation, providing equivalent signal intensity and clinical outcomes while improving procedural efficiency, supporting its use as a valid clinical option.

Humans↗

Cis-regulatory evolution of CsANS1 drives cultivar variation in anthocyanin accumulation in tea plants.

Anthocyanins, a ubiquitous class of water-soluble phytochemicals renowned for their chromatic diversity and potent bioactivity, are integral to the phenotypic and metabolic plasticity of higher plants. Using an integrative multi-omics approach that combines transcriptomic and metabolomic profiling, we identified anthocyanin synthase (CsANS1) as the key genetic determinant responsible for interspecific variation in anthocyanin accumulation among tea plants. Architectural comparison of promoter regions revealed a 192-bp variation insertion in the CsANS1 cis-regulatory region with potential functional significance. This insertion was strictly conserved in anthocyanin-rich (purple-leaf) cultivars, including both natural and hybrid genotypes, but entirely missing in anthocyanin-deficient (green-leaf) cultivars. Dual-luciferase assays confirmed that this insertion enhances promoter activity. Additionally, we delineated a tripartite regulatory axis comprising CsmiR156b, CsSPL9, and CsMYB75 which orchestrates the spatiotemporal modulation of CsANS1 expression and, consequently, anthocyanin biosynthesis. Collectively, these findings provide a mechanistic paradigm for anthocyanin polymorphism in tea plants, implicating both cis-regulatory evolution and transcriptional network synergy as pivotal drivers of phytochemical diversification.

Anthocyanins↗

Stereo-cell: Spatial enhanced-resolution single-cell sequencing with high-density DNA nanoball-patterned arrays.

Single-cell sequencing technologies have advanced our understanding of cellular heterogeneity and biological complexity. However, existing methods face limitations in throughput, capture uniformity, cell size flexibility, and technical extensibility. We present Stereo-cell, a spatial enhanced-resolution single-cell sequencing platform based on high-density DNA nanoball (DNB)-patterned arrays, which enables scalable and unbiased cell capture at a wide input range and supports high-fidelity transcriptome profiling. Stereo-cell further allows integration with imaging-based modalities and multiomics strategies, including immunofluorescence and epitope profiling. This platform is also compatible with profiling extracellular vesicles, microstructures, and large cells, whereas its spatial resolution facilitates in situ analysis of cell-cell interactions, cellular microenvironments, and subcellular transcript localization. Together, Stereo-cell provides a flexible framework for expanding single-cell research applications.

Animals↗

Emergence of crucial evidence catalyzing the origin tracing of SARS-CoV-2.

Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), its genetic and geographical origins remain unclear, resulting in suspicions about its natural origin. In one of our previous studies, we reported the presence of a furin cleavage site RRAR in the junction region between S1 and S2 subunits of the spike protein, which was discovered as the first crucial clue for the origin tracing of SARS-CoV-2. In the present study, we conducted an integrative analysis of new genome data from bat Sarbecovirus strains reported after the COVID-19 outbreak. The primary results included the identification of BANAL-20-52, Rp22DB159, and S18CXBatR24 as three close relatives of SARS-CoV-2 and the successful detection of seven out of nine key genomic features (designated as RC0-7 and ORF8) observed in wild types of SARS-CoV-2 in the three close relatives from Laos, Vietnam, and Yunnan province of China, respectively. The most significant contribution of the present study lies in the detection of RC1 in wild genotype in a bat Sarbecovirus population BANAL-20-52 belonging to. Encoding a segment of the NSP3 protein, RC1 was discovered as the second crucial clue for the origin tracing of SARS-CoV-2. Although RC0, encoding the junction furin cleavage site, remains undetected outside of the SARS-CoV-2 genome, Feuang of Laos is the sole place where eight of the nine wild-type features (RC1-7 and ORF8) have been detected.

SARS-CoV-2↗

Horizontal plasmid transfer promotes antibiotic resistance in selected bacteria in Chinese frog farms.

The emergence and dissemination of antibiotic resistance genes (ARGs) in the ecosystem are global public health concerns. One Health emphasizes the interconnectivity between different habitats and seeks to optimize animal, human, and environmental health. However, information on the dissemination of antibiotic resistance genes (ARGs) within complex microbiomes in natural habitats is scarce. We investigated the prevalence of antibiotic resistant bacteria (ARB) and the spread of ARGs in intensive bullfrog (Rana catesbeiana) farms in the Shantou area of China. Antibiotic susceptibilities of 361 strains, combined with microbiome analyses, revealed Escherichia coli, Edwardsiella tarda, Citrobacter and Klebsiella sp. as prevalent multidrug resistant bacteria on these farms. Whole genome sequencing of 95 ARB identified 250 large plasmids that harbored a wide range of ARGs. Plasmid sequences and sediment metagenomes revealed an abundance of tetA, sul1, and aph(3&#x2033;)-Ib ARGs. Notably, antibiotic resistance (against 15 antibiotics) highly correlated with plasmid-borne rather than chromosome-borne ARGs. Based on sequence similarities, most plasmids (62%) fell into 32 distinct groups, indicating a potential for horizontal plasmid transfer (HPT) within the frog farm microbiome. HPT was confirmed in inter- and intra-species conjugation experiments. Furthermore, identical mobile ARGs, flanked by mobile genetic elements (MGEs), were found in different locations on the same plasmid, or on different plasmids residing in the same or different hosts. Our results suggest a synergy between MGEs and HPT to facilitate ARGs dissemination in frog farms. Mining public databases retrieved similar plasmids from different bacterial species found in other environmental niches globally. Our findings underscore the importance of HPT in mediating the spread of ARGs in frog farms and other microbiomes of the ecosystem.

Animals↗

Genomic Study on Blood Culture Isolates From Patients With Staphylococcus Infection-associated Glomerulonephritis.

INTRODUCTION: Staphylococcus infection-associated glomerulonephritis (SAGN), is an autoimmune sequela of infection affecting a subset of infected patients without specific predictive factors, frequently presenting with acute nephritic syndrome and propensity for chronic kidney disease. We performed a comparative genotypic and phenotypic analysis of S.&#xa0;aureus isolates from patients that did and those that did not develop SAGN. METHODS: We had 22 culture-proven cases of SAGN from Ohio State University Wexner Medical Center (OSUWMC) from 2004 to 2016, 9 of 22 being blood cultures, with archived isolates. These, along with blood culture isolates from 12 patients with no clinical evidence of SAGN (between ages 40 to 80 years) over the same period were used for genotyping. For host demographic comparison, we used all available SAGN cases (n&#xa0;= 85, including those with positive cultures other than blood; and patients with kidney biopsies received from referring hospitals) and all OSUWMC patients with positive Staphylococcus cultures without glomerulonephritis (GN) (n&#xa0;= 23,496). RESULTS: Multiple sequence types (STs) suggesting strain diversity was seen in the GN isolates with mainly clonal complexes (CC) 5 and 59. Mutations in the agr operon were identified in significantly higher number of the GN isolates (83%) than non-GN isolates (16%). Significant differences in &#x3b2;-hemolysis and biofilm formation was also observed between the groups. CONCLUSION: The functionality of these agr mutants remains to be seen, but the presently known effects of reduced agr function, namely increased surface adhesins, biofilm formation, and persistent bacteremia could be important microbial factors predisposing to SAGN and testing for them early during infection could help to predict its development.

MRSA↗

Contralateral C7 transfer for the treatment of brachial plexus root avulsions in children - a report of 12 cases.

PURPOSE: To retrospectively determine the risks and benefits of contralateral C7 nerve root transfer in infants and children. METHODS: In 12 infants and children with brachial plexus root avulsions from birth injury or other trauma, the common trunk of the contralateral C7 root was transferred to the trunk, division, cord, or nerve branch(es) on the affected side with 2 different types of interposition grafts. The surgery was performed in 1 stage for 5 patients and in 2 stages for 7 patients. RESULTS: Patients were followed up for a mean of 42 months, with a minimum of 21 months. Noteworthy function (> or = M2+, modified British Medical Research Council grading system) was gained in 10 of 12 patients and sensory function (> or = S3, British Medical Research Council grading system) was gained in all patients. Improvements in strength and sensation were accompanied by little synchronous motion and sensibility changes in the donor limb in 7 children, to whom the repaired nerves were those innervating the shoulder and/or elbow or both the musculocutaneous and median nerves. In addition to slight damage to the sensory function of the median nerve, 2 infants also had temporarily reduced shoulder abduction on the healthy side. CONCLUSIONS: For contralateral C7 transfer in infants and children with brachial plexus root avulsions, the deficit created by the procedure is minimal and motor and sensory function is gained. Transfer of the contralateral C7 root to different nerves for a child may improve the quality of functional recovery. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic, Level IV.

Brachial Plexus Neuropathies↗

Discovery of phenyl acetic acid substituted quinolines as novel liver X receptor agonists for the treatment of atherosclerosis.

A structure-based approach was used to optimize our new class of quinoline LXR modulators leading to phenyl acetic acid substituted quinolines 15 and 16. Both compounds displayed good binding affinity for LXRbeta and LXRalpha and were potent activators in LBD transactivation assays. The compounds also increased expression of ABCA1 and stimulated cholesterol efflux in THP-1 cells. Quinoline 16 showed good oral bioavailability and in vivo efficacy in a LDLr knockout mouse model for lesions.

ATP Binding Cassette Transporter 1↗

Self-assembly and liquid-crystalline properties of 5-fluoroalkylporphyrins.

We report three crystal structures of a synthetic 5-fluoroalkylporphyrin molecule that was programmed for self-assembly. All the X-ray structures of zincated and free-base porphyrins Zn2 b, Zn5 a, and 2 b revealed rigorous pi-pi stacking and extremely hydrophobic interactions. Other the other hand, the strong aggregation of 5-fluoroalkylporphyrins in solution was also found. Interestingly, the regular nanopore formation of the 5-fluoroalkylporphyrin was visualized by atomic force microscopy (AFM). Importantly, the 5-fluoroalkylporphyrins possess liquid-crystalline properties that were confirmed by using a combination of differential scanning calorimetry (DSC) and polarizing optical microscopy (POM) techniques. By comparison, the self-assembly of non-fluorine-containing porphyrins with similar structure showed much lower aggregation ability, as investigated by NMR techniques. Additionally, no birefringent mesophase was observed for the non-fluorine-containing porphyrin.

Crystallography, X-Ray↗

Effect of Brillouin slow light on distributed Brillouin fiber sensors.

The effect of Brillouin slow light on distributed Brillouin fiber sensors (DBFSs) is studied. We demonstrate Brillouin slow light for a 1.2 ns pulse with peak powers (PS) from 3.3 to 56.2 mW on depletion of the pump power (PP) ranging from 1.3 to 83.2 mW in conventional optical fibers (SMF-28). Experiments show that, when pump power depletion is not negligible, for a given PP the Brillouin gain and delay time of a pulse decrease when PS increases in a long (> or =10 km) sensing fiber. The optimum pump beam depletion resulting from strong interaction of the pump and the probe in the fiber provides accurate temperature and strain information at a high spatial resolution. Our study reveals that at low PP the spatial resolution error caused by the pulse delay for a DBFS with centimeter spatial resolution is less than 5% of the pulse length.

Journal Article↗

FDJS03 isolates causing an outbreak of aseptic meningitis in China that evolved from a distinct Echovirus 30 lineage imported from countries of the Commonwealth of Independent States.

We compared echovirus 30 strains (FDJS03) which caused an outbreak of aseptic meningitis in China in 2003 with other human enterovirus B strains. Sequencing of the complete genome of FDJS03_84, a representative strain from this outbreak, revealed a mosaic structure with a putative recombination spot within the 2B gene. It was most similar to a strain of the same serotype, E30-14125-00, in the 5' half of the genome but was almost equidistant to all strains analyzed in most of the 3' half of the genome. Phylogenetic relationships in the 5'-untranslated region and the VP1 gene indicated that the FDJS03 isolates were closely related to a distinct lineage of E30 which circulated in countries of the Commonwealth of Independent States during 1999 and 2000. It is most likely that the ancestor of FDJS03 isolates experienced multiple recombination events in the nonstructural protein coding region, which were partly observed in the phylogenetic analysis of the 3D region.

5' Untranslated Regions↗

Keyhole approach surgery for petroclival meningioma.

BACKGROUND: In China, the feasibility of keyhole approach in surgical treatment of petroclival meningioma has not been well evaluated. This report summarized our experience in 25 patients with petroclival meningioma who had been treated with keyhole approach surgery. METHODS: From July 2000 to July 2005, 25 patients with petroclival meningioma were subjected to resection via subtemporal, retrosigmoid or combined keyhole approaches. The extent of tumor resection was evaluated by MRI 3 months after surgery, and postoperative complications were investigated. RESULTS: The maximum diameter of tumors ranged from 2 to 7 cm (mean, 4.5 cm). Gross total resection (GTR) was achieved in 14 patients, giving a GTR rate of 56%. Subtotal resection (STR) was carried out in 8 patients and partial resection in 3. Thirteen patients kept normal neurological status, whereas others suffered from cranial nerve deficits (VII, VII, III and lower CN). One patient died in the postoperative period. CONCLUSIONS: Keyhole approach surgery, especially the combined keyhole approach is suitable for the treatment of petroclival meningioma. It provides easy and quick access to the supra- and infratentorial juxta-clival region without drilling of the petrous bone. Complications related to the approach can be minimized.

Adult↗

Fabrication of zeolite-4A membranes on a catalyst particle level.

Zeolite-4A membranes are coated onto spherical Pt/gamma-Al2O3 particles with an average diameter of 1.5 mm, and a model oxidation reaction of a mixture of CO and n-butane (50 : 50) is used to demonstrate the concept of reactant selectivity via the coated defect-free membranes.

Journal Article↗

Liver X receptor (LXR)-beta regulation in LXRalpha-deficient mice: implications for therapeutic targeting.

The nuclear receptors liver X receptor (LXR) LXRalpha and LXRbeta are differentially expressed ligand-activated transcription factors that induce genes controlling cholesterol homeostasis and lipogenesis. Synthetic ligands for both receptor subtypes activate ATP binding cassette transporter A1 (ABCA1)-mediated cholesterol metabolism, increase reverse cholesterol transport, and provide atheroprotection in mice. However, these ligands may also increase hepatic triglyceride (TG) synthesis via a sterol response element binding protein 1c (SREBP-1c)-dependent mechanism through a process reportedly regulated by LXRalpha. We studied pan-LXRalpha/beta agonists in LXRalpha knockout mice to assess the contribution of LXRbeta to the regulation of selected target genes. In vitro dose-response studies with macrophages from LXRalpha-/- and beta-/- mice confirm an equivalent role for LXRalpha and LXRbeta in the regulation of ABCA1 and SREBP-1c gene expression. Cholesterol-efflux studies verify that LXRbeta can drive apoA1-dependent cholesterol mobilization from macrophages. The in vivo role of LXRbeta in liver was further evaluated by treating LXRalpha-/- mice with a pan-LXRalpha/beta agonist. High-density lipoprotein (HDL) cholesterol increased without significant changes in plasma TG or very low density lipoprotein. Analysis of hepatic gene expression consistently revealed less activation of ABCA1 and SREBP-1c genes in the liver of LXRalpha null animals than in treated wild-type controls. In addition, hepatic CYP7A1 and several genes involved in fatty acid/TG biosynthesis were not induced. In peripheral tissues from these LXRalpha-null mice, LXRbeta activation increases ABCA1 and SREBP-1c gene expression in a parallel manner. However, putative elevation of SREBP-1c activity in these tissues did not cause hypertriglyceridemia. In summary, selective LXRbeta activation is expected to stimulate ABCA1 gene expression in macrophages, contribute to favorable HDL increases, but circumvent hepatic LXRalpha-dominated lipogenesis.

ATP Binding Cassette Transporter 1↗

[Adriamycin and mitomycin dose-dependently downregulate X-kinked inhibitor of apoptosis protein in human bladder cancer cells].

OBJECTIVE: To investigate the efficacy of inducing apoptosis in human bladder cancer cells by adriamycin and mitomycin and relevant mechanism. METHODS: Human bladder cancer cells of the lines RT4, MGH-U1, FJ, and T24 were cultured. Adriamycin of the concentrations of 0.1, 1, and 10 microg/ml, and mitomycin of the concentrations of 0.01, 0.1, and 1 microg/ml were added into the culture fluid respectively. CCK-8 colorimetric assay was used to detect the survival rates of the cells so as to select the cell line sensitive and tolerable to the drugs. Flow cytometry was used to detect the cell apoptosis. Western blotting was used to detect the levels of X-kinked inhibitor of apoptosis protein (XIAP) and the cleavage of caspase-3 precursor. RESULTS: It was found that RT4 cells were the most sensitive and the T24 cells were the most tolerable to adriamycin and mitomycin. Treated with adriamycin of the concentrations of 0.1, 1, and 10 microg/ml for 24 hours, the apoptotic rates of the RT4 cells were 15.3% +/- 4.3%, 29.3% +/- 6.4%, and 45.0% +/- 5.5% respectively; and the apoptotic rates of the T24 cells were 7.3% +/- 3.1%, 12.5% +/- 4.3%, and 18.2% +/- 6.3% respectively, all significantly lower than those of the RT4 cells (P < 0.05 or P < 0.01). Treated with mitomycin of the concentrations of 0.01, 0.1, and 1 microg/ml for 24 hours, the apoptotic rates of the RT4 cells were 12.7% +/- 2.9%, 31.3% +/- 4.4%, and 48.9% +/- 5.8% respectively, and the apoptotic rates of the RT4 cells were 7.2% +/- 3.3%, 15.5% +/- 5.2%, and 21.2% +/- 4.4% respectively, all significantly lower than those of the RT4 cells (all P < 0.05). The XIAP expression was not significantly different in these 4 cell lines before the adriamycin and mitomycin treatment. After the treatment of adriamycin and mitomycin, the expression of XIAP was down-regulated dose-dependently, however, being weaker in the T24 cells than in the RT4 cells; and caspase-3 precursor cleavage was enhanced, however, being weaker in the T24 cells too. CONCLUSION: Adriamycin and mitomycin dose-dependently kill the human bladder cancer cells. Such cytotoxic effect may be realized through inducing the cell apoptosis which is associated with the down-regulation of XIAP and cleavage of caspase-3 precursor.

Antibiotics, Antineoplastic↗