Research progress on the immune microenvironment and immunotherapy in gastric cancer.

The tumor microenvironment, particularly the immune microenvironment, plays an indispensable role in the malignant progression and metastasis of gastric cancer (GC). As our understanding of the GC microenvironment continues to evolve, we are gaining deeper insights into the biological mechanisms at the single-cell level. This, in turn, has offered fresh perspectives on GC therapy. Encouragingly, there are various monotherapy and combination therapies in use, such as immune checkpoint inhibitors, adoptive cell transfer therapy, chimeric antigen receptor T cell therapy, antibody-drug conjugates, and cancer vaccines. In this paper, we review the current research progress regarding the GC microenvironment and summarize promising immunotherapy research and targeted therapies.

[Simultaneous determination of gestodene, etonogestrel and ethinylestradiol in plasma by LC-MS/MS following derivatization].

To establish a sensitive and specific method for simultaneous determination of gestodene, etonogestrel and ethinylestradiol in plasma by LC-MS/MS, plasma samples were extracted and derivatized before injection. An ESI ion source was used and operated in the positive ion mode with multiple reaction monitoring (MRM). Norgestrel was chosen as internal standard and performed on a C18 (100 mm x 2.1 mm, 5 microm) column. The concentrations of gestodene, etonogestrel and ethinylestradiol were measured, using step-gradient mobile phase and step-gradient flow rate. The method was validated over the concentration range of 0.1-20 ng x mL(-1) for gestodene and etonogestrel and 0.01-2 ng x mL(-1) for ethinylestradiol, and showed excellent linearity. The intra- and inter-assay accuracy and precision were below 10.0% and recovery was 93.6%-110.9% over the three concentration levels evaluated. The method was applied in pharmacokinetic study of the compound gestodene patch and the compound etonogestrel patch in rabbits. The LC-MS/MS method was selective, accurate and sensitive, especially the LOQ were 100 pg x mL(-1) for gestodene and etonogestrel and 10 pg x mL(-1) for ethinylestradiol. The method was successfully applied in pharmacokinetic study for contraceptives.

Peoniflorin attentuates Abeta((1-42))-mediated neurotoxicity by regulating calcium homeostasis and ameliorating oxidative stress in hippocampus of rats.

Peoniflorin (PEF), a monoterpene glycoside isolated from the aqueous extract of the dry root of Paeonia, possesses wide pharmacological effects in nervous system. In this study, by using a developed rat model of hippocampal dysfunction induced by intrahippocampal injection of Abeta((1-42)) oligomers, we investigated whether PEF exerted protection against Abeta-induced neurotoxicity. A stereotactic intrahippocampal bilateral injection of Abeta((1-42)) (5 microg per side) was performed in Sprague-Dawley rats (250-280 g). Abeta((1-42))-exposed rats showed remarkable memory impairment in Morris water maze test and neuronal apoptosis by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling in hippocampus. Chronic treatment with PEF (7.5, 15 and 30 mg/(kg day), for 20 days, intraperitoneally) significantly and dose-dependently attenuated cognitive deficit, ameliorated cell apoptosis in Abeta((1-42))-treated rats. The neuroprotective effect of PEF was closely associated with its activities of maintenance of [Ca(2+)](i) homeostasis, increase of reduced glutathione (GSH) content, suppression of NOS activity and nitric oxide (NO) level, decrease of carbonyl protein (CP) and malondialdehyde (MDA) levels. These results suggested that PEF possessed the activity of prevention of the neurotoxicity induced by Abeta((1-42)) and might exert beneficial action for the treatment of Alzheimer's disease (AD).

Paeonol attenuates neurotoxicity and ameliorates cognitive impairment induced by d-galactose in ICR mice.

In the present study, we examined the supplementation of paeonol extracted from Moutan cortex of Paeonia suffruticosa Andrews (MC) or the root of Paeonia lactiflora Pall (PL) on reducing oxidative stress, cognitive impairment and neurotoxicity in d-galactose (D-gal)-induced aging mice. The ICR mice were subcutaneously injected with D-gal (50 mg/(kg day)) for 60 days and administered with paeonol (50, 100 mg/(kg day)) simultaneously. The results showed that paeonol significantly improved the learning and memory ability in Morris water maze test and step-down passive avoidance test in D-gal-treated mice. Further investigation showed that the effect of paeonol on improvement of cognitive deficit was related to its ability to inhibit the biochemical changes in brains of D-gal-treated mice. Paeonol increased acetylcholine (Ach) and glutathione (GSH) levels, restored superoxide dismutase (SOD) and Na(+), K(+)-adenosine triphosphatase (Na(+), K(+)-ATPase) activities, but decreased cholinesterase AChe activity and malondialdehyde (MDA) level in D-gal-treated mice. Furthermore, paeonol ameliorated neuronal damage in both hippocampus and temporal cortex in D-gal-treated mice. These results suggest that paeonol possesses anti-aging efficacy and may have potential in treatment of neurodegenerative diseases.

Simultaneous determination of metformin and glipizide in human plasma by liquid chromatography-tandem mass spectrometry.

A method has been developed for the simultaneous quantification of metformin (I) and glipizide (II) in human plasma. It is based on high-performance liquid chromatography with electrospray ionization tandem mass (LC-ESI-MS/MS) spectrometric detection in positive ionization mode. Phenformin (III) and gliclazide (IV) were used as internal standards for I and II, respectively. The MS/MS detection was performed in multiple reaction monitoring (MRM) mode. The precursor-product ion combinations of m/z 130 --> 71, 446 --> 321, 206 --> 60 and 324 --> 127 were used to quantify I, II, III and IV, respectively. This method was validated in the concentration ranges of 0.02-4 microg/mL for I and 0.004-0.8 microg/mL for II. It was utilized to support a clinical pharmacokinetic study after single dose oral administration of a combination of I and II.

[Simultaneous determination of pseudoephedrine and chlorpheniramine in human plasma by HPLC-UV detection method].

AIM: To establish a sensitive and specific method to simultaneous determination of pseudoephedrine and chlorpheniramine in human plasma. METHODS: Pseudoephedrine and chlorpheniramine were extracted from alkaline plasma with t-butyl methyl ether as the base form, and were back-extracted into 1.5% hydrochloride solution. The two drugs were simultaneous determined by RP-HPLC with ultraviolet detection at 200 nm, using dextromethorphan as internal standard. A C18 column (250 mm x 46 mm ID) and a mobile phase containing acetonitrile-water-triethylamine (46:54:0.2, containing 10 mmol x L(-1) sodium dodecyl sulfate (SDS) and 60 mmol x L(-1) NaH2 PO4, adjusted pH to 2.6 with H3PO4) were used. RESULTS: The limit of quantification was 10.0 and 0.5 microg x L(-1), the linear range was 1.5 - 0.01 mg x L(-1) and 75 - 0.5 microg x L(-1), for pseudoephedrine and chlorpheniramine, respectively. The within-day and between-day RSD were less than 12.4%, and the average recovery was between 97.3% - 109.4%. CONCLUSION: The method was sensitive, specific, simple, and suitable for drug level monitoring in clinical pharmacokinetic study.