Imatinib-induced ulcerative colitis.

INTRODUCTION: Imatinib, a tyrosine kinase inhibitor, is the first-line therapy for patients with KIT mutation in gastrointestinal stromal tumor (GIST). Nausea, vomiting, diarrhea, dyspepsia and abdominal pain are common gastrointestinal adverse reactions of imatinib, but imatinib-induced ulcerative colitis (UC) is rarely reported. CASE REPORT: We presented a case of UC induced by imatinib in a 56-year-old male patient who experienced this adverse event after 5 years of imatinib 400 mg/d treatment following GIST resection. MANAGEMENT AND OUTCOME: The patient's diarrhea and bloody stools showed significant improvement following the discontinuation of imatinib therapy and administration of antidiarrheal medications. Then, imatinib was restarted at a daily dosage of 400 mg. DISCUSSION: UC is a rare adverse event associated with imatinib. Physicians should consider the possibility of UC induced by imatinib when patients present with diarrhea and bloody stool after receiving imatinib treatment. This case offered objective evidence of UC induced by imatinib.

Analysis of the characteristic compounds of Citri Sarcodactylis Fructus from different geographical origins.

INTRODUCTION: Citri Sarcodactylis Fructus (CSF) is widely used as a food ingredient and a traditional Chinese medicine. In China, CSF is cultivated in many places, including Sichuan, Guangdong, Zhejiang, and Fujian provinces. The types and chemical contents of CSF from different origins may vary greatly due to the difference in climate and environmental conditions. Therefore, comparing the chemical composition of CSF from various places is vital. OBJECTIVE: To rapidly select potential characteristic compounds for differentiating CSF from different origins. MATERIAL AND METHODS: Thirty-one batches of CSF samples from different regions were analysed using ultra-performance liquid chromatography with hybrid quadrupole-orbitrap high-resolution mass spectrometry. Thereafter, chemometric methods, including principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA), were employed to find differential metabolites among the CSF samples from various origins. RESULTS: PCA revealed 77.9% of the total variance and divided all CSF samples into three categories corresponding to their origins. OPLS-DA displayed better discrimination of CSF from different sources, with R2 X, R2 Y, and Q2 of 0.801, 0.985, and 0.849, respectively. Finally, 203 differential metabolites were obtained from CSF from different origins using the variable importance in projection of the OPLS-DA model, 30 of which were identified, and five coumarin compounds were selected as marker compounds discriminating CSF from different origins. CONCLUSION: This work provides a practical strategy for classifying CSF from different origins and offers a research foundation for the quality control of CSF.

Higher Circulating Trimethylamine N-oxide Sensitizes Sevoflurane-Induced Cognitive Dysfunction in Aged Rats Probably by Downregulating Hippocampal Methionine Sulfoxide Reductase A.

Gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) has recently been shown to promote oxidative stress and inflammation in the peripheral tissues, contributing to the pathogenesis of many diseases. Here we examined whether pre-existing higher circulating TMAO would influence cognitive function in aged rats after anesthetic sevoflurane exposure. Aged rats received vehicle or TMAO treatment for 3 weeks. After 2 weeks of treatment, these animals were exposed to either control or 2.6% sevoflurane for 4 h. One week after exposure, freezing as measured by fear conditioning test, microglia activity, proinflammatory cytokine expression and NADPH oxidase-dependent reactive oxygen species (ROS) production in the hippocampus (a key brain structure involved in learning and memory) were comparable between vehicle-treated rats exposed to control and vehicle-treated rats exposed to sevoflurane. TMAO treatment, which increased plasma TMAO before and 1 week after control or sevoflurane exposure, significantly reduced freezing to contextual fear conditioning, which was associated with increases in microglia activity, proinflammatory cytokine expression and NADPH oxidase-dependent ROS production in the hippocampus in rats exposed to sevoflurane but not in rats exposed to control. Moreover, hippocampal expression of antioxidant enzyme methionine sulfoxide reductase A (MsrA) was reduced by TMAO treatment in both groups, and TMAO-induced reduction in MsrA expression was negatively correlated with increased proinflammatory cytokine expression in rats exposed to SEV. These findings suggest that pre-existing higher circulating TMAO downregulates antioxidant enzyme MsrA in the hippocampus, which may sensitize the hippocampus to oxidative stress, resulting in microglia-mediated neuroinflammation and cognitive impairment in aged rats after sevoflurane exposure.

Distribution of the active components from Xianglian Pill in tissues of healthy and antibiotic-associated diarrhea model mice and the mechanism study.

Antibiotic-associated diarrhea (AAD) is a common side effect of antibiotic therapy, characterized by intestinal inflammation which reduces the quality of life of patients. Xianglian Pill (XLP) has long been used to treat abdominal pain, diarrhea, bacillary dysentery and enteritis. Studies found that XLP has curative effect on AAD; however, the chemical constituents and mechanism of XLP have not been fully elucidated because of the lack of in vitro and in vivo studies. In this study, ultra-high performance liquid chromatography mass spectrometry method (UPLC-Q-Exactive-Orbitrap-HRMS) was used to examine the components of the XLP. Then, the binding between active compounds and the key targets was studied using network pharmacology and molecular docking. A comparative tissue distribution study was established for the simultaneous determination of the 10 active components in healthy and AAD mouse models. Forty-six components were characterized from XLP. According to the network pharmacology degree value, a prediction was made that encompassed 42 components and 14 core targets, which were intricately involved in crucial biological pathways, such as the AGE-RAGE signaling, cellular senescence, and MAPK signaling. Tissue distribution analysis showed that the 10 components were widely distributed in the heart, liver, spleen, lungs, kidneys, small intestine, and large intestine of mice, with varying concentrations in healthy and AAD mice. Molecular docking analysis also indicated that the active compounds in the tissue distribution could bind tightly to key targets of network pharmacological studies. This study provides a reference for further investigations of the relationships between the chemical components and pharmacological activities of XLP.

MRI Radiomics Features From Infarction and Cerebrospinal Fluid for Prediction of Cerebral Edema After Acute Ischemic Stroke.

Neuroimaging biomarkers that predict the edema after acute stroke may help clinicians provide targeted therapies and minimize the risk of secondary injury. In this study, we applied pretherapy MRI radiomics features from infarction and cerebrospinal fluid (CSF) to predict edema after acute ischemic stroke. MRI data were obtained from a prospective, endovascular thrombectomy (EVT) cohort that included 389 patients with acute stroke from two centers (dataset 1, n = 292; dataset 2, n = 97), respectively. Patients were divided into edema group (brain swelling and midline shift) and non-edema group according to CT within 36 h after therapy. We extracted the imaging features of infarct area on diffusion weighted imaging (DWI) (abbreviated as DWI), CSF on fluid-attenuated inversion recovery (FLAIR) (CSFFLAIR) and CSF on DWI (CSFDWI), and selected the optimum features associated with edema for developing models in two forms of feature sets (DWI + CSFFLAIR and DWI + CSFDWI) respectively. We developed seven ML models based on dataset 1 and identified the most stable model. External validations (dataset 2) of the developed stable model were performed. Prediction model performance was assessed using the area under the receiver operating characteristic curve (AUC). The Bayes model based on DWI + CSFFLAIR and the RF model based on DWI + CSFDWI had the best performances (DWI + CSFFLAIR: AUC, 0.86; accuracy, 0.85; recall, 0.88; DWI + CSFDWI: AUC, 0.86; accuracy, 0.84; recall, 0.84) and the most stability (RSD% in DWI + CSFFLAIR AUC: 0.07, RSD% in DWI + CSFDWI AUC: 0.09), respectively. External validation showed that the AUC of the Bayes model based on DWI + CSFFLAIR was 0.84 with accuracy of 0.77 and area under precision-recall curve (auPRC) of 0.75, and the AUC of the RF model based on DWI + CSFDWI was 0.83 with accuracy of 0.81 and the auPRC of 0.76. The MRI radiomics features from infarction and CSF may offer an effective imaging biomarker for predicting edema.

Physakengose G induces apoptosis via EGFR/mTOR signaling and inhibits autophagic flux in human osteosarcoma cells.

BACKGROUND: Physakengose G (PG) is a new compound first isolated from Physalis alkekengi var. franchetii, an anticarcinogenic traditional Chinese medicine. PG has shown promising anti-tumor effects, but its underlying mechanisms remain unknown. PURPOSE: To investigate the anti-cancer effects of PG on human osteosarcoma cells and the underlying mechanisms. METHODS: Cell viability was measured by MTT assay. Apoptosis rates, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation, and acidic vesicular organelles (AVOs) formation were determined by flow cytometry. Protein levels were analyzed by immunofluorescence and western blotting. RESULTS: PG inhibited cell proliferation and induced apoptosis in human osteosarcoma cells. PG treatment blocked EGFR phosphorylation and suppressed epidermal growth factor (EGF)-induced activation of downstream signaling molecules, such as AKT and mTOR. PG treatment resulted in lysosome dysfunction by altering lysosome acidification and LAMP1 levels, which led to autophagosome accumulation and autophagic flux inhibition. CONCLUSION: PG inhibits cell proliferation and EGFR/mTOR signaling in human osteosarcoma cells. Moreover, PG induces apoptosis through the mitochondrial pathway and impedes autophagic flux via lysosome dysfunction. Our findings indicate that PG has the potential to play a significant role in the treatment of osteosarcoma.

Physakengoses K-Q, seven new sucrose esters from Physalis alkekengi var. franchetii.

Seven sucrose esters, physakengoses K-Q (1-7) were isolated from the aerial parts of Physalis alkekengi var. franchetii. Their structures were elucidated on the basis of extensive spectroscopic analyses and chemical methods. These new compounds were tested for their antimicrobial abilities against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Escherichia coli. Among the isolated sucrose esters, compounds 1-5 showed potent antibacterial activity with MIC values ranging from 2.16 to 12.76 µg/mL.

1H NMR spectroscopy-guided isolation of new sucrose esters from Physalis alkekengi var. franchetii and their antibacterial activity.

Ten new sucrose esters, physakengoses A-J (1-10), were isolated from the aerial parts of Physalis alkekengi var. franchetii under the guidance of 1H NMR spectroscopy. Their structures were determined by spectroscopic analyses (HRESIMS, 1D and 2D NMR, and ESIMS) and chemical methods. These new compounds were tested for antibacterial activities against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Escherichia coli. Among them, compounds 2 and 5-8 showed potent inhibitory effects against test strains with MIC values ranging from 3.5 to 14.9µg/mL. These findings may indicate that the P. alkekengi var. franchetii has potential application as an ingredient in pharmaceuticals.