Biomedical subjects

Yi Fan

Publications and source records attributed to Yi Fan.

At least 19 recordsLinked to original sources

PubMed2025

Repression of PRMT activities sensitize homologous recombination-proficient ovarian and breast cancer cells to PARP inhibitor treatment.

Therapeutic epigenetic modulation is currently being evaluated in the clinic to sensitize homologous recombination (HR)-proficient tumors to PARP inhibitors. To broaden its clinical applicability and identify more effective combination strategies, we conducted a drug screen combining PARP inhibitors with 74 well-characterized epigenetic modulators targeting five major classes of epigenetic enzymes. Notably, both type I PRMT inhibitors and PRMT5 inhibitors scored highly in combination efficacy and clinical prioritization. PRMT inhibition significantly enhanced PARP inhibitor-induced DNA damage in HR-proficient ovarian and breast cancer cells. Mechanistically, PRMT suppression downregulates DNA damage repair genes and BRCAness-associated pathways, while also modulating intrinsic innate immune responses within cancer cells. Integrative analysis of large-scale genomic and functional datasets from TCGA and DepMap further supports PRMT1, PRMT4, and PRMT5 as promising therapeutic targets in oncology. Importantly, dual inhibition of PRMT1 and PRMT5 synergistically sensitizes tumors to PARP inhibitors. Collectively, our findings provide strong rationale for the clinical development of PRMT and PARP inhibitor combinations in HR-proficient ovarian and breast cancers.

Journal Article↗

PubMed2006

Aquaporin 4 regulates the effects of ovarian hormones on monoamine neurotransmission.

Aquaporin 4 (AQP4) is the predominant water channels in the brain of mammals. Our previous study has reported that AQP4 knockout induced sex-specific alterations in neurotransmission, indicating that AQP4 might regulate the interaction between sex hormones and neurotransmission. In the present study, we found that AQP4 knockout decreased the concentrations of estrogen and progestogen. Further study showed that exogenous estrogen decreased DA and 5-HT in cortex, reduced DA and 5-HT in striatum, but increased 5-HT in hippocampus in AQP4+/+ male mice. However, in AQP4-/- male mice, exogenous estrogen almost did not alter the levels of neurotransmitters except for decreasing DA in cortex. In female mice, ovariectomy decreased DA in the striatum of AQP4+/+ mice, but did not alter the levels of DA in AQP4-/- mice. These findings reveal for the first time that AQP4 regulates not only water and ion homeostasis but also the functions of ovarian hormone and neurotransmitter.

Animals↗

PubMed2006

Aquaporin-4 deficiency down-regulates glutamate uptake and GLT-1 expression in astrocytes.

The role of aquaporin-4 in water transport has been extensively investigated, while little information exists regarding its contribution to astrocytic functions such as the action to glutamatergic transmission. Since aquaporin-4 has been detected widely co-localized with glutamate transporter 1 (GLT-1) and glutamate transporters also present water transport properties, we investigated the regulative role of aquporin-4 on glutamate transporter using primary cultured astrocytes from aquaporin-4 knockout (AQP4(-/-)) mice. It was demonstrated that lack of aquaporin-4 down-regulated astrocytic expression of GLT-1 but not of glutamate/aspartate transporter (GLAST). The result from [(3)H]D,L-glutamate uptake analysis showed a lower uptake capability in AQP4(-/-) astrocytes. Furthermore, MTT and LDH assays indicated less cellular toxicity induced by excessive glutamate in AQP4(-/-) genotype. These findings provide direct evidences for the first time that aquaporin-4 plays an important role in the function of glutamate transporters. And the present study will improve our understanding of aquaporin-4-glutamanergic biology.

Animals↗

PubMed2006

[Regulation effect of d-alpha-tocopherol on the expression of hexokinase induced by high glucose in cultured human peritoneal mesothelium cells].

OBJECTIVE: To investigate the effect of d-alpha-tocopherol on the expression of hexokinase (HK) induced by high glucose in cultured human peritoneal mesothelium cell (HPMC). METHODS: Specimens of human omentum were obtained from consenting patient undergoing elective abdominal surgery. HPMC were isolated and subcultured by enzymatic disaggregation. Morphology and immunocytochemical method were used for identification. HPMC were divided into normal glucose group (0.1% glucose, equal to 5.5 mmol/L), high glucose group (0.5%, 1.0%, 1.5%, 2.5%, 4.25% glucose) and d-alpha-tocopherol group. After 24 h, standard G6PDH-coupled assay, temperature sensitive essay were used to detect the activity of total HK and its isozyme. Immunocytochemical staining was used for observation the intracellular location of HKII. Western blotting was used to analyze the protein expression of HKII and RT-PCR was used to detect the mRNA expression of HKII. The net glucose utilization was assayed by glucose disappearance from medium by hexokinase method. RESULTS: Primary cultured HPMC reacted positively for cytokeratin and vimentin and had numerous surface microvilli under electron microscope. High glucose induced HK activity in a dose-dependent manner and increased HKII isoform selectively. At concentration of 1.5%, 2.5% and 4.25% glucose for 24 h, the relative activity of total HK were 115.4%, 129.1% and 155.2%, respectively comparing with normal control (P < 0.05), and selectively increased HKII isoform expression. D-alpha-tocopherol blocked the activity of total HK and HKII induced by glucose. The relative activity of total HK inhibited by d-alpha-tocopherol was 82.1% (P = 0.001). After incubated with d-alpha-tocopherol, the net glucose utilization were decreased from (25.3 +/- 3.9) mmol/L to (17.3 +/- 2.1) mmol/L (P = 0.018). HKII stained light brown in cytoplasm of HPMC in normal group, accompanying with the increased concentration of glucose, the staining of HKII became strong and accumulated to nuclear. D-alpha-tocopherol made it thinning. The protein and mRNA expression of HKII were accorded with its activity. CONCLUSION: D-alpha-tocopherol inhibited the expression of HKII in activity, protein and mRNA induced by high glucose and decreased the net glucose utilization, which might become a method to improve ultrafiltration in peritoneal dialysis.

Cell Line↗

PubMed2005

Sex- and region-specific alterations of basal amino acid and monoamine metabolism in the brain of aquaporin-4 knockout mice.

Aquaporin-4 (AQP4), a predominant water channel of the brain, mediates transmembrane water movement at the blood-brain barrier and brain-cerebrospinal fluid interface. A broad pattern of evidence indicates that AQP4 and regulators of its expression are potential targets for treatment of brain swelling, but whether it participates in the regulation of neurotransmission has not been reported. We examined neurochemical differences between AQP4-knockout and wild-type mice with particular focus on neurotransmission. Basal tissue neurotransmitter and metabolite levels were measured by high-performance liquid chromatography. Significant sex- and region-specific differences of amino acids and monoamines were found in the brain of wild-type and AQP4-knockout mice. In cortex, striatum, and hippocampus of male AQP4-knockout mice, an increase of glutamine and decrease of aspartate were observed. Glutamate was increased only in female AQP4-knockout mice. The lack of AQP4 failed to affect the levels of gamma-aminobutyric acid and taurine. In the medial prefrontal cortex of AQP4-knockout mice, the levels of serotonin and norepinephrine were increased, but no significant change in dopamine level was found. In the striatum of male AQP4-knockout mice, the levels of dopamine and serotonin were remarkably increased, which was not found in female mice. In the hypothalamus of AQP4-knockout mice, only the serotonin level was altered. These results provide the first evidence that the lack of AQP4 expression is accompanied by sex- and region-specific alterations in brain amino acid and monoamine metabolism.

Amino Acids, Basic↗

PubMed2005

Biocompatible in-tube solid-phase microextraction coupled to HPLC for the determination of angiotensin II receptor antagonists in human plasma and urine.

A poly (methacrylic acid-ethylene glycol dimethacrylate, MAA-EGDMA) monolithic capillary was used for the in-tube solid-phase microextraction (in-tube SPME) of several angiotensin II receptor antagonists (ARA-IIs) from human plasma and urine. Under the optimized extraction condition, the protein component of the biological sample was flushed through the monolithic capillary, while the analytes were successfully trapped. Coupled to HPLC with fluorescence detection, this on-line in-tube SPME method was successfully applied for the determination of candesartan, losartan, irbesartan, valsartan, telmisartan, and their detection limits were found to be 0.1-15.3ng/mL and 0.1-15.2ng/mL in human plasma and urine, respectively. The method was linear over the range of 0.5-200ng/mL for telmisartan, 5-2000ng/mL for candesartan and irbesartan, 10-2000ng/mL for valsartan, and 50-5000ng/mL for losartan with correlation coefficients being above 0.9985 in plasma sample and above 0.9994 in urine sample. The method reproducibility was evaluated at three concentration levels, resulting in the R.S.D. <7%. The poly (MAA-EGDMA) monolithic capillary was demonstrated to be robust and biocompatible by using direct injections of biological samples.

Angiotensin Receptor Antagonists↗

PubMed2005

Poly(acrylamide-vinylpyridine-N,N'-methylene bisacrylamide) monolithic capillary for in-tube solid-phase microextraction coupled to high performance liquid chromatography.

In-tube solid-phase microextraction (SPME) based on a poly(acrylamide-vinylpyridine-N,N'-methylene bisacrylamide) monolithic capillary was investigated and on-line coupled to HPLC for the determination of trace analytes in aqueous samples. The polymer monolith was conveniently synthesized in a fused silica capillary by in situ polymerization method. Several groups of analytes including non-steroidal anti-inflammatory drugs, phenols, non-peptide angiotensin II receptor antagonists and endocrine disrupting chemicals were extracted by the monolithic capillary. High extraction efficiency was achieved for the analytes investigated and great improvement of the limits of detection were obtained in comparison to that of direct chromatographic analysis and strong hydrophobic and ion-exchange interactions between the analytes and the polymer were confirmed. The newly developed monolithic capillary showed excellent reusability and high stability under extreme pH conditions during extraction. The possibility of applying the established method to water sample analysis was also demonstrated.

Chromatography, High Pressure Liquid↗

PubMed2005

[Regulation of hexokinase activity by protein kinase C in peritoneal mesothelium cell].

OBJECTIVE: To investigate the effect of protein kinase C (PKC) on the activity of hexokinase (HK) in rat peritoneal mesothelium cell (PMC) and the functional consequences in glucose uptake. METHODS: omentum obtained from albino male rats of the Sprague Dawley strain, PMC were isolated and subculture by enzymatic disaggregation. The antibody to cytokeratin was used for identified by immunofluorescence technique. After treated with PKC activator--phorbol esters (PMA and PDD) and classical PKC (cPKC) inhibitor--Gö6976, total HK activity in PMC were measured by a standard G6PDH-coupled assay, glucose disappearance in the culture medium were tested as glucose net utilization by colorimetric method. RESULTS: The PMC were polygonal when confluent and reacted positively for cytokeratin. PMA induced HK activity in a time and dose-dependent manner and increased net glucose utilization. At concentration of 0.01, 0.1 and 1 micromol/L PMA for 24 h, the increase in HK activity were 30.7%, 59.9% and 99.1%, respectively above the level in the control (P < 0.05). After treated with 1 micromol/L PMA for 6 h, the HK activity of PMC began to up-regulation, the peak reached at 24 h (21.3% vs 100.4%, P < 0.05), and accompanied by increase in net glucose utilization (2 mmol/L, P < 0.05). The expression of HK induced by 0.1 micromol/L PDD were similar to 1 micromol/L PMA, 4 alpha-PDD whose structure resemble to PDD didn't have effect on HK. Gö6976 blocked the activity of HK induced by PMA. After incubated with Gö6976 at concentration of 10, 20, 30, 40 and 50 micromol/L for 30 min, PMC were cultured in 1 micromol/L PMA for 24 h, the decrease in HK activity were 14.6%, 26.8%, 34.2%, 44.2% and 54.9% (P < 0.05). CONCLUSIONS: Elevated HK activity by PKC was accompanied with corresponding increase in net glucose utilization, which might take part in the accelerated glucose uptake after long-term peritoneal dialysis. The blocking of HK activity by cPKC inhibitor might be an effective method for increasing ultrafiltration in peritoneal dialysis.

Animals↗

PubMed2005

Poly(methacrylic acid-ethylene glycol dimethacrylate) monolith in-tube solid phase microextraction coupled to high performance liquid chromatography and analysis of amphetamines in urine samples.

In-tube solid-phase microextraction (SPME) based on a poly(methacrylic acid-ethylene glycol dimethacrylate) monolithic capillary column was investigated for the extraction of amphetamine, methamphetamine and their methylenedioxy derivatives. The monolithic capillary column showed high extraction efficiency towards target analytes, which could be attributed to its larger loading amount of extraction phase than conventional open-tubular extraction capillaries and the convective mass transfer procedure provided by its monolithic structure. The extraction mechanism was studied, and the results indicated that the extraction process of the target analytes was involved with hydrophobic interaction and ion-exchange interaction. The polymer monolith in-tube SPME-HPLC system with UV detection was successfully applied to the determination of amphetamine, methamphetamine and their methylenedioxy derivatives in urine samples, yielding the detection limits of 1.4 - 4.0 ng/mL. Excellent method reproducibility (RSD < 2.9%) was found over a linear range of 0.05-5 microg/mL, and the time for the whole analysis was only approximately 25 min. The monolithic capillary column was reusable in coping with the complicated urine samples.

Adsorption↗

PubMed2005

Determination of endocrine disruptors in environmental waters using poly(acrylamide-vinylpyridine) monolithic capillary for in-tube solid-phase microextraction coupled to high-performance liquid chromatography with fluorescence detection.

A method for the determination of endocrine disruptors, bisphenol A and 17alpha-ethinylestradiol, in environmental water samples was developed using in-tube solid-phase microextraction followed by liquid chromatography and fluorescence detection. A poly(acrylamide-vinylpyridine) monolithic capillary column was applied as the extraction media in view of its greater phase ratio than open-tubular capillaries and thus higher extraction efficiency. After optimizing the extraction conditions, bisphenol A and 17alpha-ethinylestradiol were extracted directly from water samples in a wide dynamic linear range of 0.5-1000 ng mL(-1), with the detection limits obtained as 0.064 and 0.12 ng mL(-1), respectively. The precision of the method was satisfactory with the intraday and interday RSD values smaller than 7.2%. Environmental water samples of different sources were successfully analyzed with the presented method and the monolithic capillary was proved to be robust and reusable in analyzing real water samples.

Benzhydryl Compounds↗

PubMed2005

Determination of camptothecin and 10-hydroxycamptothecin in human plasma using polymer monolithic in-tube solid phase microextraction combined with high-performance liquid chromatography.

A biocompatible in-tube solid-phase microextraction (SPME) device was used for the direct and on-line extraction of camptothecin and 10-hydroxycamptothecin in human plasma. Biocompatibility was achieved through the use of a poly(methacrylic acid-ethylene glycol dimethacrylate) monolithic capillary column for extraction. Coupled to high performance liquid chromatography (HPLC) with UV detection, this on-line in-tube SPME method was successfully applied to the simultaneous determination of camptothecin and 10-hydroxycamptothecin in human plasma. The calculated detection limits for camptothecin and 10-hydroxycamptothecin were found to be 2.62 and 1.79 ng/mL, respectively. The method was linear over the range of 10-1000 ng/mL. Excellent method reproducibility was achieved, yielding RSDs of 2.49 and 1.59%, respectively. The detection limit (S/N = 3) of camptothecin was found to reach 0.1 ng/mL using fluorescence detection. The proposed method was shown to cope robustly with the extraction and analysis of camptothecin and 10-hydroxycamptothecin in plasma samples.

Camptothecin↗

PubMed2005

Functionalized polydiacetylene-glycolipid vesicles interacted with Escherichia coli under the TiO2 colloid.

The interaction of the conjugated system between functionalized polydiacetylene-glycolipid vesicles and Escherichia coli was investigated under the bactericidal effect of TiO(2) colloid. With various pre-incubation and irradiation time, controllable bacteria quantity in the presence of TiO(2) colloid was obtained in real time. UV-visible and Raman spectra were utilized to monitor and evaluate the structural transition of bacteria-polydiacetylene-glycolipid vesicles conjugated system under the different conditions, which supplied the detailed information of the transform of the polydiacetylene backbone in real time. Thus controllable conjugated bio-interaction between two bio-interfaces was obtained through the introduction of the third factor and monitored in real time. This would be great aid in fundamental understanding more complex interfaces in the biological environment and would be applicable to the biomedical and biophysical fields.

Acetylene↗

PubMed2005

Poly(methacrylic acid-ethylene glycol dimethacrylate) monolith in-tube solid-phase microextraction applied to simultaneous analysis of some amphetamine derivatives in urine by capillary zone electrophoresis.

A method based on in-tube solid-phase microextraction and capillary zone electrophoresis (CZE) was proposed for simultaneously determining four amphetamines (amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, and 3,4-methylenedioxymethamphetamine) in urine. A poly(methacrylic acid-ethylene glycol dimethacrylate) monolithic capillary column, which can provide sufficient extraction efficiency, was introduced for the extraction of amphetamines from urine samples. The hydrophobic main chains and acidic pendant groups of the monolithic column make it a superior material for extraction of basic analytes from aqueous matrix. After extraction, the samples were analyzed by CZE. The best separation was achieved using a buffer composed of 0.1 M disodium hydrogen phosphate (adjusted to pH 4.5 with 1 M hydrochloric acid) and 20% methanol v/v, with a temperature and voltage of 25 degrees C and 20 kV, respectively. By applying electrokinetic injection with field-amplified sample stacking, detection limits of 25-34 microg/L were achieved. Excellent method of reproducibility was found over a linear range of 0.1-5 mg/L. Determination of these analytes from abusers' urine sample was also demonstrated.

Amphetamines↗

PubMed2004

In-tube solid-phase microextraction with poly(methacrylic acid-ethylene glycol dimethacrylate) monolithic capillary for direct high-performance liquid chromatographic determination of ketamine in urine samples.

Ketamine was used for anaesthesia originally but has emerged as an abused drug in recent years. The prevalence of ketamine abuse demands a direct and rapid determination method. It is known that in-tube solid phase microextraction (in-tube SPME) can perform extraction with a capillary linked directly to a HPLC system, providing an automated and accurate extraction procedure. In this paper, an in-tube SPME coupled to HPLC method was developed for the determination of ketamine in urine samples with a poly(methacrylic acid-ethylene glycol dimethacrylate) monolithic capillary column as the extraction phase, which is expected to provide higher extraction efficiency than open tubular capillaries. After optimizing the extraction conditions, ketamine was extracted directly from urine samples in a wide dynamic linear range of 50-10,000 ng mL(-1), with the detection limit obtained as 6.4 ng mL(-1). The intra-day and inter-day precision for the method was 1.6% and 1.7%, respectively. The urine samples from suspect addicts have been successfully analyzed within 20 min. The re-usability of the monolithic column was also confirmed as no decrease of the extraction efficiency was shown after urine extraction.

Chromatography, High Pressure Liquid↗

PubMed2004

CT biliary cystoscopy of gallbladder polyps.

AIM: CT virtual endoscopy has been used in the study of various organs of body including the biliary tract, however, CT virtual endoscopy in diagnosis of gallbladder polyps has not yet been reported. This study was to evaluate the diagnostic value of CT virtual endoscopy in polyps of the gallbladder. METHODS: Thirty-two cases of gallbladder polyps were examined by CT virtual endoscopy, ultrasound, CT scan with oral biliary contrast separately and confirmed by operation and pathology. CT biliary cystoscopic findings were analyzed and compared with those of ultrasound and CT scan with oral biliary contrast, and evaluated in comparison with operative and pathologic findings in all cases. RESULTS: The detection rate of gallbladder polyps was 93.8%(90/96), 96.9%(93/96) and 79.2%(76/96) for CT cystoscopy, ultrasound and CT scan with oral contrast, respectively. CT biliary cystoscopy corresponded well with ultrasound as well as pathology in demonstrating the location, size and configuration of polyps. CT endoscopy was superior to ultrasound in viewing the polyps in a more precise way, 3 dimensionally from any angle in space, and showing the surface in details. CT biliary cystoscopy was also superior to CT scan with oral biliary contrast in terms of observation of the base of polyps for the presence of a pedicle, detection rates as well as image quality. The smallest polyp detected by CT biliary cystoscopy was measured 1.5 mm x 2.2 mm x 2.5 mm. CONCLUSION: CT biliary cystoscopy is a non-invasive and accurate technique for diagnosis and management of gallbladder polyps.

Adult↗

PubMed2004

[The primary comparative analysis between the host genetic factors and their relationships with clinical phenotype of HBV infected twins].

OBJECTIVE: The primary comparative analysis between the host genetic factors and their relationships with clinical phenotype of 20 pairs of HBV infected and high risk twins. METHODS: Zygosity of twins was diagnosed by STR microsatellite polymorphism analysis. To identify the serological model and exclude the evidence of coinfection with other virus, we detected HAV, HBV, HCV, HDV, HEV serological markers by electrochemiluminescence method. HBV DNA level was detected by Lightcycler Fluorescent Quantitative system and Liver function (ALT, AST, TBil) was detected by HITACHI7250 Biochemistry Detection System. The data was analysis by Fisher's exact test to comparatively analyze among the monozygotic twins (MZ), dizygotic twins (DZ) and control groups. RESULTS: The significant difference was found in the concordance rate of disease, concordance of clinical phenotype and serological patterns of HBV infection between the MZ and DZ twins (P < 0.05), it was also found between MZ and control groups (P < 0.05), but not between DZ and control groups (P > 0.05). No significant difference in the concordance of other HBV infection markers was observed (P > 0.05). Concordance of clinical phenotype may be related to patients' age and antivirus therapy. Injection with the HBIg and initiative vaccination right after birth can prevent twins with high risk to infection to be victims. CONCLUSION: The significant difference was found in the concordance rate, concordance of clinical phenotype and serological patterns between MZ and control groups, it was also found between MZ and DZ groups, which is correspond to the opinion of the high concordance of MZ and indicated the host genetic factors may play role in influencing the clinical phenotype, while other factors such as the vaccination may have an effect on the clinical phenotype in some extent.

DNA, Viral↗

PubMed2004

Mannose-Escherichia coli interaction in the presence of metal cations studied in vitro by colorimetric polydiacetylene/glycolipid liposomes.

Supramolecular assemblies of liposomes (vesicles) made of diacetylenic lipids and synthetic mannoside derivative glycolipid receptors were successfully used to mimic the molecular recognition occurring between mannose and Escherichia coli. This specific molecular recognition was translated into visible blue-to-red color transition (biochromism) of the polymerized liposomes, readily quantified by UV-visible spectroscopy. Some transition metal cations (Cd(2+), Ag(+), Cu(2+), Fe(3+), Zn(2+) and Ni(2+)) and alkali earth metal cations (Ca(2+), Mg(2+) and Ba(2+)) were introduced into the system to analyze their effects on specific biochromism. Results showed that the presence of Cd(2+), Ag(+), Ca(2+), Mg(2+) and Ba(2+) enhanced biochromism. A possible enhancement mechanism was proposed in the process of bacterial adhesion to host cells. However, Cu(2+), Fe(3+), Zn(2+) and Ni(2+) exhibited inhibitory effects that cooperated with diacetylene lipid with a carboxylic group and increased the rigidity of the liposomal outer leaflet, blocking changes in the side chain conformation and electrical structure of polydiacetylene polymer during biochromism.

Acetylene↗

PubMed2004

IFN-gamma activates cAMP/PKA/CREB signaling pathway in murine peritoneal macrophages.

Interferon-gamma (IFN-gamma) is a macrophage-activating cytokine that serves critical functions in innate and adaptive immunity and is thought to be mediated by the Jak-Stat signaling pathway. The present study establishes for the first time that cyclic adenosine monophosphate, protein kinase A, and cAMP response element-binding protein (cAMP/PKA/CREB) are coregulators of the IFN-gamma signaling pathway. Experimental data indicate that exogenous IFN-gamma stimulated cAMP accumulation and PKA activation in time-dependent and dose-dependent manners in murine peritoneal macrophages. Moreover, IFN-gamma stimulated CREB phosphorylation and CREB DNA binding, which could be significantly attenuated by PKA inhibition with H89. It appears that a novel cAMP/PKA/CREB signaling pathway is activated by IFN-gamma in macrophages, suggesting that an alternate signaling pathway exists in macrophages in response to IFN-gamma.

Animals↗