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Xiaohui Chen

Publications and source records attributed to Xiaohui Chen.

10 recordsLinked to original sources

Cell-type specific activation of the cGAS-STING pathway in tumor immunotherapy: mechanisms and therapeutic implications.

BACKGROUND: The cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS–STING) pathway acts as a pivotal innate immune sensor that detects cytosolic DNA and links genomic instability to antitumor immune activation. Therapeutic activation of this pathway has garnered substantial interest as a strategy to enhance cancer immunotherapy by promoting dendritic cell maturation, augmenting antigen presentation, and facilitating cytotoxic lymphocyte infiltration. However, the functional outcomes of cGAS–STING signaling are highly context dependent and influenced by both cell type and tumor microenvironmental (TME) conditions. MAIN BODY: Recent advances in single-cell and spatial transcriptomic profiling have revealed profound heterogeneity in cGAS–STING activation across distinct cellular and regional compartments within tumors. Acute and spatially restricted activation of the pathway can elicit potent antitumor immune responses, whereas chronic or dysregulated signaling may promote immune tolerance and tumor progression. Moreover, metabolic stress, epigenetic silencing, and microenvironmental immunosuppressive factors such as TGF-β and IL-10 can further modulate STING activity, leading to resistance to immunotherapy. Current translational efforts focus on next-generation STING agonists, nanoparticle-based delivery systems, and rational combination strategies with immune checkpoint blockade and metabolic modulators to overcome tumor-intrinsic resistance and minimize systemic toxicity. CONCLUSIONS: Understanding the cell-type-specific and spatial dynamics of cGAS–STING signaling is crucial for the rational design of precision immunotherapies. Future research should emphasize context-dependent modulation of STING activity to maximize therapeutic benefit while limiting adverse effects. Integrating multi-omics technologies and spatially guided drug delivery may ultimately enable personalized modulation of the cGAS–STING axis, transforming it into a clinically effective and safe strategy for cancer immunotherapy.

Humans↗

BNArray: an R package for constructing gene regulatory networks from microarray data by using Bayesian network.

UNLABELLED: BNArray is a systemized tool developed in R. It facilitates the construction of gene regulatory networks from DNA microarray data by using Bayesian network. Significant sub-modules of regulatory networks with high confidence are reconstructed by using our extended sub-network mining algorithm of directed graphs. BNArray can handle microarray datasets with missing data. To evaluate the statistical features of generated Bayesian networks, re-sampling procedures are utilized to yield collections of candidate 1st-order network sets for mining dense coherent sub-networks. AVAILABILITY: The R package and the supplementary documentation are available at http://www.cls.zju.edu.cn/binfo/BNArray/.

Algorithms↗

[Simultaneous determination of five isoflavonoids in commercial Radix Astragali by high performance liquid chromatography].

A reversed-phase high performance liquid chromatographic method (RP-HPLC) was developed for the simultaneous analysis of five isoflavonoids of Huangqi, the roots of Astragalus mongholicus. HPLC determination was performed on a Diamonsil C18 column (200 mm x 4.6 mm i.d., 5 microm) and detected at 230 nm. The mobile phase consisted of (A) acetonitrile and (B) water. Gradient program was adopted as follows: 0-25 min from 17% A to 31% A, 25 -45 min 35% A. The flow rate was maintained at 1.0 mL/min. The method was proved to be linear in the ranges of 20.12-201.2 mg/L (r = 0.9992), 4.62-46.2 mg/L (r = 0.9997), 4.86 -48.6 mg/L (r = 0.9997), 9.24-92.4 mg/L (r = 0.9995) and 6.92-69.2 mg/L (r = 0. 999 5) for the five isoflavonoids, calycosin-7-O-beta-D-glucoside, formononetin-7-O-beta-D-glucoside,9,10-dimethoxypterocarpan-3-O-beta-D-glucoside, calycosin and formononetin, respectively. The recoveries were greater than 94%, and relative standard deviations were less than 3.2%. The method has been successfully applied to the simultaneous determination of the five isoflavonoids of radix astragali.

Astragalus Plant↗

LC-MS determination and pharmacokinetic studies of ursolic acid in rat plasma after administration of the traditional chinese medicinal preparation Lu-Ying extract.

Sambucus chinensis L. is a native perennial herb distributed throughout China. In traditional Chinese medicine (TCM), this herb is known as Lu-Ying. Ursolic acid is the major effective constituent of Lu-Ying. A rapid, sensitive, and accurate liquid chromatography-mass spectrometry (LC-MS) method for the determination of ursolic acid in rat plasma was developed and validated. Plasma samples taken from rats that had received Lu-Ying extract orally were acidified with acetic acid and then extracted with a mixture of hexane-dichloromethane-2-propanol (20:10:1, v/v/v). Separation of ursolic acid was accomplished on a C(18) column interfaced with a single quadrupole mass spectrometer. The mobile phase consisting of methanol and water (95:5, v/v) was delivered at a flow rate of 1.0 ml/min. Atmospheric pressure chemical ionization was operated in negative-ion mode. Using selected ion-monitoring mode, the deprotonated molecules [M-H](-) at m/z 455 and 469 were used to quantify ursolic acid and glycyrrhetic acid (internal standard), respectively. The assay was shown to be linear over the range of 10-1000 ng/ml (r> or =0.9960) with a lower limit of quantification of 10 ng/ml. The method was shown to be reproducible and reliable with intraday precision below 7.8%, interday precision below 8.1%, accuracy within +/-4.3%, and mean extraction recovery excess of 83.6%, which were all calculated from the blank plasma sample spiked with ursolic acid at three concentrations of 20, 200, and 800 ng/ml. The LC-MS method has been successfully applied to pharmacokinetic studies of ursolic acid after oral administration of Lu-Ying ethanolic extract (at a dose containing 80.32 mg/kg ursolic acid) to rats. The main pharmacokinetic parameters were: t(1/2), 4.3 h; K(e), 0.16 1/h; t(max), 1.0 h; C(max), 294.8 ng/ml; AUC(0-t) and AUC(0-infinity), 1007.1 ng.h/ml and 1175.3 ng.h/ml, respectively.

Administration, Oral↗

Analysis of the essential oil from radix bupleuri using capillary gas chromatography.

A simple and rapid capillary gas chromatographic (CGC) method with flame ionization detection has been newly developed for analysis of the essential oil from Radix Bupleuri. Twenty components were identified with gas chromatography-mass spectrometry. E-2-heptenal, furan, 2-pentyl, and E-2-nonenal were quantified simultaneously using the internal standard method. Decane was used as an internal standard. Separation and quantification were achieved on a DB-5 capillary column (30 m x 0.25 mm i. d., 0.25-microm film thickness). The oven temperature was programmed as follows: 60 degrees C to 70 degrees C at 1 degree C/min rate, 70 degrees C for 10 min, 3 degrees C/min to 120 degrees C, 20 degrees C/min to 250 degrees C, and held at 250 degrees C for 5 min. The oven pressure was programmed as follows: 46.1 kPa for 25 min, 20.0 kPa/min to 77.6 kPa, and then held for 22 min. Split injection was conducted with a split ratio of 10:1; flow-rate, 1.00 ml/min; carrier gas, nitrogen; injector temperature, 280 degrees C; and detector temperature, 280 degrees C. The system proved effective in resolving E-2-heptenal, furan, 2-pentyl, and E-2-nonenal peaks from their interfering components. The method displayed excellent linearity in the range of 26.8-1072 microg/ml (E-2-heptenal), 6.5-1292 microg/ml (furan, 2-pentyl), and 7.8-1564 microg/ml (E-2-nonenal). The average recovery rates of E-2-heptenal, furan, 2-pentyl, and E-2-nonenal were 100.3%, 102.8%, and 97%, respectively. CGC is a quick and accurate method for analysis of the essential oil from Radix Bupleuri.

Bupleurum↗

[Isolation and preparation of sesquiterpenols from the Japanese cedar, Cryptomeria japonica D. Don, by preparative reversed-phase high performance liquid chromatography and its characterization].

A method for the isolation of sesquiterpenols from the Japanese Cedar, Cryptomeria japonica D. Don by preparative reversed-phase high performance liquid chromatography (RP-HPLC) was established. The preparation of the sesquiterpenols was carried out on a preparative liquid chromatograph with a YWC-Pack C18 column, and the mobile phase was isopropanol-methanol-hexane-water (50:35:10:5, v/v) at a flow rate of 5.0 mL/min. The two sesquiterpenols, (-)-cubebol and (+)-2,7(14),10-bisabolatrien-1-ol-4-one, were separated by liquid chromatography and identified by spectroscopic analyses (ultraviolet (UV), infrared (IR), nuclear magnetic resonance (NMR), electrospray ionization mass spectrometry (ESI-MS)). The purities of the two sesquiterpenols were 98.7% and 99.1%, respectively.

Chromatography, High Pressure Liquid↗

[High performance liquid chromatographic determination of cinnamic acid in rabbit plasma and application in study of pharmacokinetics].

A high performance liquid chromatographic method was developed to determine the content of cinnamic acid in rabbit plasma and the method was utilized for the study of pharmacokinetics. Cinnamic acid was separated by employing a column of Kromasil C18 (250 mm x 4.6 mm i.d., 5 microm) and a mobile phase of methanol-acetonitrile-water-glacial acetic acid (10:22:55:0.5, v/v) at a flow rate of 0.8 mL/min and room temperature with UV detection at 270 nm and phenylpropionic acid as internal standard. The extraction recoveries of the spiked samples at low, middle and high levels were 84.9%, 84.4% and 87.7%, respectively, while the method recoveries were 98.4% with relative standard deviation (RSD) of 5.5%, 99.2% with RSD of 3.6%, 100.1% with RSD of 3.7% in turn. The RSDs of intra-day and inter-day were both lower than 6%. Finally, the metabolism of cinnamic acid in rabbit plasma after medication of Guanxin Suhe Wan and Guanxin Suhe Capsule fitted in a first order absorption of two-compartment model. The method was found to be sensitive, accurate and precise, and is appropriate for the determination of cinnamic acid.

Animals↗

Reverse-phase HPLC determination and pharmacokinetic study of vanillic acid in the plasma of rats treated with the traditional Chinese medicinal preparation Di-Gu-Pi decoction.

A sensitive, simple, and accurate method for the determination and pharmacokinetic study of vanillic acid in rat plasma was developed using reverse-phase HPLC with UV detection after oral administration of the traditional Chinese medicine preparation of the Di-Gu-Pi decoction. Plasma samples taken from rats were extracted with methanol. The constituent vanillic acid was separated on a C(18) stationary phase and a mobile phase of acetonitrile-water (15:85, v/v) (adjusted to pH 3.0 using phosphoric acid), with a UV detector setting at 260 nm. The validated HPLC method developed was used to determine the pharmacokinetic profile of vanillic acid in rat plasma after administration of the Di-Gu-Pi decoction.

Administration, Oral↗

Prostate targeting ligands based on N-acetylated alpha-linked acidic dipeptidase.

To identify inhibitors of the intrinsic N-acetylated alpha-linked acidic dipeptidase (NAALADase) activity of prostate specific membrane antigen (PSMA) that may be useful for targeting imaging agents or chemotherapeutic drugs to disseminated prostate cancer, analogs of the tetrahedral transition state for hydrolysis of the natural substrate, N-acetylaspartylglutamate (NAAG), were synthesized. These compounds were assayed for their ability to inhibit the membrane-associated enzyme isolated from LNCaP prostate cancer cells. Active inhibitors were further assayed for their cytotoxicity and membrane binding. We have identified nine compounds, including fluorescent and iodine-labeled conjugates, which inhibit NAALADase enzyme activity with IC(50)s at, or below, 120nM. The binding of these compounds to the cell surface of viable LNCaP prostate tumor cells appears to be specific and saturable, and none of the compounds alter the cell cycle kinetics or induce apoptosis in LNCaP cells, suggesting that they are relatively innocuous and are suitable for targeting imaging agents or cytotoxic drugs to disseminated prostate cancer.

Antigens, Neoplasm↗