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Yuan Yuan

Publications and source records attributed to Yuan Yuan.

At least 19 recordsLinked to original sources
PubMed2026

Evolutionary patterns and repeated adaptive strategies of deep-sea anemones.

Sea anemones occupy the full depth range of the oceans, yet their evolutionary patterns and adaptive strategies to the enigmatic deep sea have remained contentious and poorly resolved. Here, we assemble genomes (n = 13) and transcriptomes for 15 species collected between 432 and 6,000 m and integrate them with publicly available actiniarian data. We find support for a shallow-water origin of Actiniaria through a framework that emphasizes genome-scale changes associated with habitat transitions. Most strikingly, these changes include repeated dismantling of the circadian toolkit across deep-sea lineages. In addition to convergent gene losses in photo- and temperature-regulatory genes, we find that some deep-sea lineages have experienced recurrent loss or pseudogenization of key meiotic genes (e.g., Meiosin, Ythdc2, Spo11, and Mlh3), suggesting reduced meiotic capacity in some lineages. Despite this extensive genomic erosion, deep-sea anemones exhibit molecular tuning: specific amino acid substitutions improve enzyme performance under low-temperature conditions relevant to the deep sea, while selective expansions of gene families related to neural excitability, membrane systems, and other functions may help maintain physiological performance in this environment. Functional assays in yeast indicate enhanced performance of the deep-sea variants at 4°C. These results define a "loss-optimization-innovation" triad that underlies bathymetric adaptations and may apply to other deep-sea fauna worldwide.

Actiniaria↗
PubMed2026

TMEM176B is co-expressed with TMEM176A and upregulated in peripheral blood monocytes of patients with primary Sjögren's syndrome.

OBJECTIVES: This study aims to determine the role of acid‑sensitive nonspecific cation channels transmembrane protein 176A (TMEM176A) and TMEM176B in autoimmune diseases, with a focus on primary Sjögren's Syndrome (pSS). METHODS: We examined the expression patterns of TMEM176A and TMEM176B across tissues and cells utilizing bulk RNA-seq and scRNA-seq datasets. Immunophenotyping analysis was performed by flow cytometry to compare CD62L expression between TMEM176B⁺ and TMEM176B⁻ monocytes. The proportion of TMEM176B+ cells in monocytes was interrogated in both pSS patients and healthy controls. Clinical correlations of TMEM176B with anti‑SSB antibody and complement C4 levels were also evaluated. RESULTS: TMEM176A and TMEM176B showed conserved co‑expression and were significantly upregulated in autoimmune diseases. TMEM176B⁺ monocytes displayed higher CD62L positivity rate than TMEM176B- monocytes. In pSS patients, the proportion of TMEM176B⁺ monocytes was elevated in total monocytes, classical monocytes (cMo) and intermediate monocytes (iMo). The proportion of TMEM176B+ monocytes positively correlated with anti‑SSB levels, while several TMEM176B-associated monocyte subset markers inversely correlated with C4. CONCLUSION: TMEM176A and TMEM176B are highly correlated. TMEM176B expression in monocytes is linked to pSS and may serve as a novel auxiliary diagnostic biomarker.

Humans↗
PubMed2026

Optimal dose and exercise modality to improve HbA1c in older adults with type 2 diabetes mellitus: a systematic review with pairwise, network, and dose-response meta-analyses.

We aimed to compare exercise modalities and evaluate dose-response relationships with glycemic control including continuous aerobic exercise (CAE), resistance training (RT), combined exercise (CE), mind-body exercise (MBE), and high-intensity interval training (HIIT) in older adults with type 2 diabetes mellitus (T2DM). Three databases were searched for randomized controlled trials of exercise interventions in older adults with T2DM reporting glycated hemoglobin (HbA1c). Pairwise, Bayesian network, and dose-response meta-analyses were conducted. Compared with control, HIIT demonstrated the largest estimated reduction (MD = -0.95%; 95% CrI -1.45, -0.49), followed by CE (MD = -0.59%; 95% CrI -0.93, -0.25), CAE (MD = -0.46%; 95% CrI -0.69, -0.24), MBE (MD = -0.42%; 95% CrI -0.76, -0.10), and RT (MD = -0.29%; 95% CrI -0.51, -0.08). Dose-response network meta-analyses suggested a non-linear association between overall exercise dose and HbA1c reduction, with maximal estimated benefits at approximately 704 METs-min/week with the 95% CrI excluding zero between 241 and 920 METs-min/week. HIIT demonstrated the steepest estimated dose-response relationship, but with wider credible intervals. Other exercise modalities showed more gradual dose-response patterns across their estimated effective ranges. Our findings suggest that exercise prescription for older adults with T2DM should be individualized according to exercise modality, dose, and health status.

Humans↗
PubMed2026

Column switching liquid chromatography dual mass spectrometry system for simultaneous untargeted metabolomics and targeted exposomics.

Exposome-wide association studies (ExWAS) require the detection of metabolites and exposures with diverse chemical properties across wide concentration ranges, a task that typically demands multiple analytical methods. To address this challenge, we develop an integrated column-switching two-dimensional liquid chromatography-dual mass spectrometry (2DLC-dual-MS) system. This system employs a 2DLC setup to sequentially separate polar and non-polar compounds with log P ranging from -8 to 15. The separated fractions are directed via a three-way valve to a high-resolution MS (HRMS) and a triple quadrupole MS (TQMS), enabling simultaneous untargeted metabolome analysis and targeted quantification of 601 exposures. The method is particularly suited for the concurrent analysis of metabolome and exposome in human blood, where their concentrations typically differ by 2-3 orders of magnitude. In a demonstration application on lung adenocarcinoma ExWAS, the system exhibits good stability over more than 300 consecutive injections for both metabolome and exposome analysis, confirming its robustness for ExWAS applications.

Metabolomics↗
PubMed2026

Ifebemtinib plus garsorasib in previously treated metastatic colorectal cancer with KRASG12C mutation: a multicentre, randomised, phase 1b/2 trial.

BACKGROUND: Ifebemtinib is a potent oral focal adhesion kinase inhibitor. Preclinical evidence supports combining ifebemtinib with the KRASG12C inhibitor garsorasib. This study aimed to evaluate this combination in KRASG12C-mutated solid tumours. METHODS: This multicentre, phase 1b/2 study had a phase 1b component to establish the recommended phase 2 dose and a phase 2 multitumour expansion component. In phase 1b, the safety and tolerability of ifebemtinib combined with garsorasib was assessed using a 3 + 3 design in KRASG12C-mutated solid tumours. No dose-limiting toxic effects were observed, and the recommended phase 2 dose was established as ifebemtinib 100 mg orally once daily plus garsorasib 600 mg orally twice daily. Here, we report the results of the cohort of previously treated KRASG12C-mutated metastatic colorectal cancer from phase 2 expansion. Eligible patients (aged ≥18 years) who had histologically confirmed locally advanced or metastatic colorectal cancer harbouring the KRASG12C mutation, an Eastern Cooperative Oncology Group performance-status score of 0 or 1, and had disease progression after previous irinotecan-based or oxaliplatin-based combination therapy, were recruited from seven of nine participating tertiary hospitals in China. On the basis of the recommended phase 2 dose, phase 2 comprised a single-arm study to evaluate the safety and efficacy of ifebemtinib combined with garsorasib and an open-label, randomised study in which patients were randomly assigned (1:1) to receive ifebemtinib plus garsorasib or garsorasib alone, by use of centralised computer-generated block randomisation with no stratification. Investigators were masked to the block size. The primary efficacy endpoint of phase 2 was investigator-assessed objective response rate (Response Evaluation Criteria in Solid Tumours, version 1.1), assessed in the safety analysis set in the single-arm study and in all randomly assigned patients (intention-to-treat population) in the randomised study. At least six objective responses (safety analysis set) were required in the single-arm study to proceed to the randomised study. This study is registered with ClinicalTrials.gov, NCT06166836 and NCT05379946, and is active but not recruiting. FINDINGS: Between April 7, 2023 and Dec 13, 2024, 51 patients were enrolled in phase 2 (15 in the single-arm study and 36 in the randomised study). In the single-arm study, the median age was 53 years (IQR 39 to 63), nine (60%) patients were female, six (40%) were male, and all were Asian. In the randomised study, the median age was 51 years (IQR 42 to 59) in the combination group and 63 years (IQR 54 to 66) in the monotherapy group, 24 (67%) were female, 12 (33%) were male, and all patients were Asian. In the single-arm part, the confirmed objective response rate was 46·7% (95% CI 21·3 to 73·4). Seven patients had partial responses, triggering progression to the randomised study. In the randomised study, the confirmed objective response rate was 38·9% (95% CI 17·3 to 64·3) with the combination therapy versus 16·7% (95% CI 3·6 to 41·4) with garsorasib alone (between-group difference 22·2%, 95% CI -7·7 to 49·1; one-sided p=0·068). In the single-arm study, grade 3 treatment-related adverse events occurred in four (27%) of 15 patients, and in the randomised study, grade 3 treatment-related adverse events occurred in six (33%) of 18 patients in the combination group and five (28%) of 18 in the garsorasib group. Grade 3 treatment-related adverse events occurring in at least two patients were diarrhoea (six [18%]), proteinuria (two [6%]), and intestinal obstruction (two [6%]) in patients treated with combination therapy (combined), and increased alanine aminotransferase and γ-glutamyltransferase (two [11%] each) in patients treated with garsorasib alone. Serious adverse events occurred in ten (30%) patients in the combination group and in four (22%) patients in the monotherapy group. One patient in the garsorasib monotherapy group died due to the underlying malignancy within 30 days after completing study treatment, which was reported as a serious adverse event. The death was assessed by the investigators as not related to garsorasib. No grade 4 treatment-related adverse events or treatment-related deaths were reported across all cohorts. INTERPRETATION: The combination of ifebemtinib and garsorasib showed promising anticancer activity and manageable safety profile in previously treated patients with KRASG12C-mutated metastatic colorectal cancer. Although the improvement in response rate did not reach statistical significance in the randomised study, these findings support further evaluation of ifebemtinib plus garsorasib in this population. FUNDING: InxMed, InventisBio, National Natural Science Foundation of China, the Jian Bing Ling Yan + X Research and Development Program of Zhejiang Province, and the Zhejiang Province Medical and Health Science and Technology Plan Project.

Humans↗
PubMed2025

Reprogramming neuroblastoma by diet-enhanced polyamine depletion.

Neuroblastoma is a highly lethal childhood tumour derived from differentiation-arrested neural crest cells1,2. Like all cancers, its growth is fuelled by metabolites obtained from either circulation or local biosynthesis3,4. Neuroblastomas depend on local polyamine biosynthesis, and the inhibitor difluoromethylornithine has shown clinical activity5. Here we show that such inhibition can be augmented by dietary restriction of upstream amino acid substrates, leading to disruption of oncogenic protein translation, tumour differentiation and profound survival gains in the Th-MYCN mouse model. Specifically, an arginine- and proline-free diet decreases the amount of the polyamine precursor ornithine and enhances tumour polyamine depletion by difluoromethylornithine. This polyamine depletion causes ribosome stalling, unexpectedly specifically at codons with adenosine in the third position. Such codons are selectively enriched in cell cycle genes and low in neuronal differentiation genes. Thus, impaired translation of these codons, induced by combined dietary and pharmacological intervention, favours a pro-differentiation proteome. These results suggest that the genes of specific cellular programmes have evolved hallmark codon usage preferences that enable coherent translational rewiring in response to metabolic stresses, and that this process can be targeted to activate differentiation of paediatric cancers.

Animals↗
PubMed2006

Preparation of hemoglobin-loaded nano-sized particles with porous structure as oxygen carriers.

Hb (hemoglobin)-loaded particles (HbP) encapsulated by a biodegradable polymer used as oxygen carrier were prepared. A modified double emulsion and solvent diffusion/evaporation method was adopted. All experiments were performed based on two types of biodegradable polymers, poly(epsilon-caprolactone) (PCL) and poly(epsilon-caprolactone-ethylene glycol) (PCL-PEG). The biodistribution and the survival time in blood of the particles were investigated in a mouse model. Encapsulation efficiency and pore-connecting efficiency were evaluated by a novel sulfocyanate potassium method. The influence of process parameters on the particle size and pore-connecting efficiency (PCE%) of nanoparticles have been discussed. The prepared conditions: solvent, external aqueous phase, pressure were discussed. The system utilizing dichloromethane (DCM)/ethyl acetate (EA) as a solvent with an unsaturated external aqueous phase yielded the highest encapsulation efficiency (87.35%) with a small mean particle size (153 nm). The formation of porous channels was attributed to the diffusion of solvent. The PCE% was more sensitive to the rate of solvent diffusion that was obviously affected by the preparation temperature. The PCE% reached 87.47% when PCL-PEG was employed at 25 degrees C. P(50) of HbP was 27 mmHg, which does not seem to be greatly affected by the encapsulation procedure. In vivo, following intravenous injection of 6-coumarin labeled HbP, the major organ accumulating Hb-loaded particles was the liver. The half-life of nano-sized PCL HbP was 3.1 times as long as the micro-sized PCL HbP. Also, Nano-sized as well as a PEGylated surface on HbP is beneficial for prolonged blood residence (7.2 fold increase).

Animals↗
PubMed2006

[Dynamic monitoring of serum pepsinogen among high risk populations of gastric cancer in Zhuanghe county].

OBJECTIVE: To investigate the dynamic changes of serum pepsinogen (PG) among the high risk populations of gastric cancer. METHODS: Peripheral blood samples were collected from 444 subjects in the high risk areas of gastric cancer in Zhuanghe county, Liaoning province, who underwent screening of gastric cancer, 225 males and 219 females, aged 48.31 (21 - 76). ELISA was used to measure the serum PG I and PG II. The PG I/II ratio was calculated. Gastroscopy was conducted to take 4 pieces of biopsy specimens from each subject to undergo pathological examination. Histological examination and serum Hp-IgG antibody determination by ELISA were performed to detect the infection of Helicobacter pylori (Hp). The above mentioned examinations were carried out at the first screening and 6, 12, and 30 months later during follow-up. RESULTS: (1) In the age group 51 - 60, the percentage change in PG II of 6-month follow-up was 0.84, significantly lower than those of the 12-month follow-up (1.22, P = 0.019) and 30-month follow-up (1.24, P = 0.004), and the percentage change in PG I/II of the 6-month follow-up was 1.09, significantly higher than those of the 12-month follow-up (0.75, P = 0.027) and 30-month follow-up (0.69, P = 0.001). However, there were no significant differences in serum PG I, serum PG II, and PG I/II ratio in other age groups. (2) The percentage change in serum PG I of the patients of superficial gastritis (SG) with mitigation of the 6-month follow-up was 0.69, significantly lower than that of the 12-month follow-up (0.97, P = 0.002). The percentage change in PG I/II of the patients of atrophic gastritis (AG) with mitigation of the 6-month follow-up was 1.13, significantly higher than that of the 12-month follow-up (0.75, P = 0.042). (3) The percentage change in PG I of the SG-->NOR (normal) group was 0.94, significantly higher than that of the SG-->AG group (0.79, P = 0.002). The percentage changes in PG I and PG II of the AG-->NOR group were 0.43 and 0.60 respectively, both significantly lower than those of the AG-->SG group (0.87, P = 0.000, and 1.11, P = 0.010). (4) The percentage change in PG I of the Hp negative-->Hp positive group was 0.94, significantly higher than that of the Hp negative-->Hp negative group (0.81, P = 0.026). The percentage changes in PG I and PG II of the Hp positive-->Hp negative group were 0.74 and 0.86 respectively, both significantly lower than those of Hp positive-->Hp positive group (0.93 and 1.15 respectively, both P = 0.000), and the percentage change in PG I/II of the Hp positive-->Hp negative group was 0.90, significantly higher than that of the Hp positive-->Hp positive group (0.70, P = 0.022). CONCLUSION: The percentage change of serum PG is correlated with time of follow-up, feature of stomach disease, and status of Hp infection. Dynamic detection of serum PG can be applied in monitoring the populations in high risk area of gastric cancer.

Adult↗
PubMed2006

Selective promoter recognition by chlamydial sigma28 holoenzyme.

The sigma transcription factor confers the promoter recognition specificity of RNA polymerase (RNAP) in eubacteria. Chlamydia trachomatis has three known sigma factors, sigma(66), sigma(54), and sigma(28). We developed two methods to facilitate the characterization of promoter sequences recognized by C. trachomatis sigma(28) (sigma(28)(Ct)). One involved the arabinose-induced expression of plasmid-encoded sigma(28)(Ct) in a strain of Escherichia coli defective in the sigma(28) structural gene, fliA. The second was an analysis of transcription in vitro with a hybrid holoenzyme reconstituted with E. coli RNAP core and recombinant sigma(28)(Ct). These approaches were used to investigate the interactions of sigma(28)(Ct) with the sigma(28)(Ct)-dependent hctB promoter and selected E. coli sigma(28) (sigma(28)(Ec))-dependent promoters, in parallel, compared with the promoter recognition properties of sigma(28)(EC). Our results indicate that RNAP containing sigma(28)(Ct) has at least three characteristics: (i) it is capable of recognizing some but not all sigma(28)(EC)-dependent promoters; (ii) it can distinguish different promoter structures, preferentially activating promoters with upstream AT-rich sequences; and (iii) it possesses a greater flexibility than sigma(28)(EC) in recognizing variants with different spacing lengths separating the -35 and -10 elements of the core promoter.

Artificial Gene Fusion↗
PubMed2006

Reversal of RNA missplicing and myotonia after muscleblind overexpression in a mouse poly(CUG) model for myotonic dystrophy.

RNA-mediated pathogenesis is a recently developed disease model that proposes that certain types of mutant genes produce toxic transcripts that inhibit the activities of specific proteins. This pathogenesis model was proposed first for the neuromuscular disease myotonic dystrophy (DM), which is associated with the expansion of structurally related (CTG)(n) and (CCTG)(n) microsatellites in two unrelated genes. At the RNA level, these expansions form stable hairpins that alter the pre-mRNA splicing activities of two antagonistic factor families, the MBNL and CELF proteins. It is unclear which altered activity is primarily responsible for disease pathogenesis and whether other factors and biochemical pathways are involved. Here, we show that overexpression of Mbnl1 in vivo mediated by transduction of skeletal muscle with a recombinant adeno-associated viral vector rescues disease-associated muscle hyperexcitability, or myotonia, in the HSA(LR) poly(CUG) mouse model for DM. Myotonia reversal occurs concurrently with restoration of the normal adult-splicing patterns of four pre-mRNAs that are misspliced during postnatal development in DM muscle. Our results support the hypothesis that the loss of MBNL1 activity is a primary pathogenic event in the development of RNA missplicing and myotonia in DM and provide a rationale for therapeutic strategies designed either to overexpress MBNL1 or inhibit MBNL1 interactions with CUG and CCUG repeat expansions.

Alternative Splicing↗
PubMed2006

[Genetic regulatory pathway of gene related breast cancer metastasis: primary study by linear differential model and k-means clustering].

OBJECTIVE: To investigate the potential genetic regulatory pathway of gene related breast cancer metastasis. METHODS: Microarray technique was used to identify the gene expression profile and to screen the differential expression genes in breast cancer with special emphasis on the metastasis factors. A gene chip was available, obtained from the surgical samples, including breast cancer primary tissues and metastasis tissues, of 30 female patients with breast cancer at different clinical stages. Then potential genetic regulatory pathway of gene related breast cancer metastasis was analyzed with a linear differential model and k-means clustering. RESULTS: Twenty-seven differential expression genes were identified. It was suggested that the potential regulatory pathway of gene related to breast cancer metastasis is made up of GRP, BPAG1, and SFRP2 genes. CONCLUSION: The metastasis of breast cancer is related to the cancerization caused by the abnormal expression of multiple genes. It is reliable to analyze the Genetic regulatory pathway of gene related breast cancer metastasis by using multiple bio-informatic measures.

Breast Neoplasms↗
PubMed2006

Degradation of mono-fluorophenols by an acclimated activated sludge.

Acclimated activated sludge was examined for its ability to degrade mono-fluorophenols as the sole carbon source in aerobic batch cultures. The acclimated activated sludge degraded fluorophenol efficiently. It degraded 100 mg/l 3-fluoropheno and 4-fluorophenol in 16 h with, respectively, 99.85% and 99.91% fluoride anion release and it degraded 50 mg/l 2-fluorophenol in 15 h with 99.26% fluoride anion release. The aerobic biodegradability of the mono-fluorophenols decreased in the order: 4-fluorophenol > 3-fluorophenol > 2-fluorophenol, resulting mainly from a different octanol/water partition coefficient and different steric parameter of the fluorophenols. The mechanism study revealed that the initial step in the aerobic biodegradation of mono-fluorophenols by the activated sludge was their transformation to fluorocatechol. Following transformation of the fluorophenol to fluorocatechol, ring cleavage by catechol 1, 2-dioxygenases proceeded via an ortho-cleavage pathway, then defluorination occurred.

Aerobiosis↗
PubMed2006

[The application of stapling device in surgery of carcinoma of the esophagus and cardia].

OBJECTIVE: To evaluate the application of circular stapler in upper digestive tract reconstruction. METHODS: We present a retrospective review of 3322 patients with Carcinoma of esophagus and cardia undergoing a stapled esophagogastric anastomosis from August 1980 to September 2004. There were 2642 males and 680 females with age ranged from 28 to 83 years old. Carcinoma of esophagus was present in 2312 patients and carcinoma of gastric cardia in 1010 patients. The anastomosis was performed in the cervical region in 102 cases, thoracic apex in 147 cases, up aortic in 1838 cases and below aortic in 1235 cases. RESULTS: Anastomotic leakage occurred in 18 patients with an overall incidence of 0.54%, including thoracic leakage in 11 cases and cervical leakage in 7 cases. nine patients were dead because of the thoracic leakage, and the mortality of thoracic leakage was 81.8%. Benign anastomotic stricture was found in 66 patients with a rate of 2.0%, and instrumental failure occurred in 36 patients with a rate of 1.1%. CONCLUSION: Circular stapler can be used safely and reliably in upper digestive tract surgery, and the stapled anastomosis is an effective technique to reduce the incidence of anastomotic leakage.

Adult↗
PubMed2006

Failure of MBNL1-dependent post-natal splicing transitions in myotonic dystrophy.

In myotonic dystrophy (DM), expression of RNA containing expanded CUG or CCUG repeats leads to misregulated alternative splicing of pre-mRNA. The repeat-bearing transcripts accumulate in nuclear foci, together with proteins in the muscleblind family, MBNL1 and MBNL2. In transgenic mice that express expanded CUG repeats, we show that the splicing defect selectively targets a group of exons that share a common temporal pattern of developmental regulation. These exons undergo a synchronized splicing switch between post-natal day 2 and 20 in wild-type mice. During this post-natal interval, MBNL1 protein translocates from a predominantly cytoplasmic to nuclear distribution. In the absence of MBNL1, these physiological splicing transitions do not occur. The splicing defect induced by expanded CUG repeats in mature muscle fibers is closely reproduced by deficiency of MBNL1 but not by deficiency of MBNL2. A parallel situation exists in human DM type 1 and type 2. MBNL1 is depleted from the muscle nucleoplasm because of sequestration in nuclear foci, and the associated splicing defects are remarkably similar to those observed in MBNL1 knockout mice. These results indicate that MBNL1 participates in the post-natal remodeling of skeletal muscle by controlling a key set of developmentally regulated splicing switches. Sequestration of MBNL1, and failure to maintain these splicing transitions, has a pivotal role in the pathogenesis of muscle disease in DM.

Alternative Splicing↗
PubMed2006

Identification of human liver cytochrome P450 enzymes responsible for the metabolism of lonafarnib (Sarasar).

Lonafarnib (Sarasar), a farnesyl transferase inhibitor, is currently under development for the treatment of solid tumors. Incubation of lonafarnib with human liver microsomes resulted in the formation of four oxidative metabolites (M1, M2, M3, and M4). Minor to trace levels of these metabolites were detected in humans after multiple-dose administration of lonafarnib. Liquid chromatography-mass spectrometry analyses exhibited a mass to charge ratio (m/z) for the (M+H)(+) ion of M1, M2, M3, and M4 at 653, 635, 669, and 653 Th, respectively. These metabolites, respectively, resulted from changes of +O, -2H, +2O, and +O relative to lonafarnib. Recombinant human CYP3A4 and CYP3A5 exhibited catalytic activity with respect to the formation of M1, M2, and M3, whereas CYP2C8 exhibited catalytic activity with respect to the formation of M4. There was a high correlation between the formation of M1, determined in 10 human liver microsomal samples, and 6beta-hydroxylation of testosterone catalyzed by CYP3A4/5 (r = 0.93). The IC(50) values of ketoconazole for inhibition of M1 and M2 were 0.61 and 0.92 microM, respectively. The formation of M4 by human liver microsomes was inhibited 72% by 50 microM quercetin, suggesting that the formation of M4 was mediated via CYP2C8. A CYP3A4/5-specific inhibitory monoclonal antibody inhibited the formation of M1, M2, and M3 by 85, 75, and 100%, respectively. In conclusion, the formation of metabolites M1, M2, and M3 from lonafarnib was mediated via CYP3A4 and CYP3A5.

Antineoplastic Agents↗
PubMed2006

[Progress on breast cancer metastasis suppressor 1 (BRMS1)].

Tumour metastasis is a significant contributor to death in cancer patients. So studies on the molecular mechanism of tumor metastasis can provide new prognostic and therapeutic methods. Tumor metastasis suppressor gene is a kind of genes that only suppresses metastasis without affecting tumorigenicity and tumor growth. BRMS1 is a tumor metastasis suppressor gene discovered in breast carcinoma cells in 2000. Its protein product was found to also suppress metastasis of melanoma cells and murine mammary carcinoma cells. BRMS1 is located in the nucleus,and interacts with mSin3-HDAC complex, and can alter the connexin expression profile of breast carcinoma cells, thereby restoring cell-cell communication via gap junctions. This review highlights some recent progress in the study of BRMS1, gives a brief introduction of related genes, and predicts its possible mechanism of action.

Animals↗
PubMed2006

[Expression and significance of interleukin-8 cyclooxygenase-2 and trefoil family factor 1 in the remnant stomach mucosa].

OBJECTIVE: To study the expression and significance of interleukin-8 (IL-8), cyclooxygenase-2 (COX-2) and trefoil family factor 1 (TFF1) in the remnant stomach mucosa. METHODS: Patients after gastrectomy were examined by upper gastrointestinal endoscopy. Biopsy specimens were obtained from stoma and the greater curvature of the upper corpus to be assessed for Hp (by H.E. and Giemsa staining) and conduct real-time semi-quantitative PCR. mRNA was extracted from the biopsy specimens to determine the IL-8, COX-2 and TFF1 gene mRNA levels by real-time PCR method. RESULTS: In the stoma, COX-2 level in Hp-positive patients was significantly higher than that in Hp-negative patients, but the difference of IL-8 levels between them was not significant. In the corpus, IL-8 and COX-2 levels in Hp-positive patients were significantly higher than those in Hp-negative patients. In Hp-negative patients, IL-8 and COX-2 levels in the stoma were significantly higher in B II anastomosis than in B I anastomosis cases; COX-2 level in the stoma was significantly higher in B II anastomosis than in B I anastomosis cases, but the difference of IL-8 levels between them was not significant. TFF1 level in the remnant stomach mucosa showed no significant difference between Hp-positive and Hp-negative patients. CONCLUSION: Hp infection and bile reflux are important risk factors for the secondary stomach carcinogenesis. Expression of IL-8 and COX-2 in the remnant stomach mucosa is related to the risk of secondary stomach carcinogenesis. The relationship between the TFF1 expression and secondary stomach carcinogenesis in the remnant stomach mucosa is still unclear and should further be studied.

Adult↗