Molecular, biological characterization and drug sensitivity of chidamide-resistant MCF7 cells.

Background: Chidamide (CHI) is a subtype-selective histone deacetylase inhibitor (HDACI) developed in China and approved as a second-line treatment combined with the aromatase inhibitor for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. However, drug resistance is commonly occurred after a long period of medication. This study aimed to investigate the characterization of induced resistance to CHI and explore the potential cross-resistance to chemotherapeutic agents. Methods: CHI with gradually increasing concentrations was added to breast cancer MCF7 cells to establish a CHI-resistant MCF7 (MCF7-CHI-R) cell line. Cell counting kit-8 (CCK-8) assays were performed to detect half-maximal inhibitory concentration (IC50) of CHI. Colony formation was used to determine the proliferation inhibition rate. Western blot analysis was conducted to detect expressions of protein related with cell cycle, apoptosis, ferroptosis, and histone deacetylase (HDAC). Flow cytometry was used to analyze apoptosis and cell cycle. Results: The IC50 value of CHI of MCF7-CHI-R cells was increased in comparison with MCF7 cells. And CHI led to cell cycle arrest and ferroptosis, which were not exhibited in MCF7-CHI-R cells. Moreover, HDAC activity decreased in MCF7-CHI-R cells in comparison with MCF7 cells, and HDAC1 and HDAC10 might be involved in the resistance to CHI. In addition, MCF7-CHI-R cells were resistant to gemcitabine (GEM), doxorubicin (ADM), docetaxel (DXT), albumin-bound paclitaxel (nab-PTX) and paclitaxel (PTX). Conclusions: The MCF7-CHI-R was established and the anti-ferroptosis pathway activation was involved in the resistance of MCF-CHI-R cells. Also, MCF7-CHI-R cells were resistant to GEM, ADM, DXT, nab-PTX and PTX.

Efficacy and safety of gemcitabine plus raltitrexed or S-1 versus standard third-line therapies in metastatic colorectal cancer: a retrospective cohort study.

Background: After the failure of standard first- and second-line treatments, including oxaliplatin, irinotecan, and 5-fluorouracil (5-FU) combined with targeted drugs, the currently recommended third-line regimens for metastatic colorectal cancer (mCRC) include TAS-102, regorafenib, and fruquintinib. However, these regimens have the drawbacks of mediocre efficacy, substantive side effects, and high cost. Therefore, more effective, economical regimens with fewer side effects are needed in clinical practice. In this study, we assessed the efficacy and safety of gemcitabine plus raltitrexed or S-1 as a third- or later-line treatment in comparison to those of standard third-line therapies for patients with mCRC. Methods: Patients with previous failures of at least two lines of standard therapy with oxaliplatin, 5-FU, irinotecan, or capecitabine combined with targeted drugs were included. The participants received standard third-line therapies (including TAS-102, regorafenib, and fruquintinib) or gemcitabine plus raltitrexed or S-1 until disease progression, death, or intolerable toxicity arose. Imaging follow-up was performed every 3 months during their treatment. Progression-free survival (PFS) and overall survival (OS) were recorded. Cox regression analysis was used to investigate the potential predictors of survival. Results: From April 2018 to October 2022, 60 patients with mCRC were enrolled in our study. The numbers of patients in the chemotherapy, fruquintinib, regorafenib, and TAS-102 groups were 13, 15, 17, and 15, respectively; the median OS of the four groups was 7.4, 6.1, 8.3, and 6.7 months (P=0.384), respectively; the median PFS was 4.1, 3.4, 4.4, and 2.3 months (P=0.656), respectively; the overall response rate was 7.69%, 6.67%, 0.00%, and 13.33%, respectively; and the disease control rate was 61.54%, 60.00%, 70.59%, and 60.00%, respectively. Additionally, multivariate analysis revealed that primary lesion located in the rectum was adverse independent prognostic factors for OS. A typical case is presented in this article. Conclusions: The gemcitabine plus raltitrexed or S-1 regimen is a potential regimen with tolerable adverse reactions and low cost for patients with mCRC.

Construction and validation of a prognostic model based on autophagy-related genes for hepatocellular carcinoma in the Asian population.

BACKGROUND AND OBJECTIVE: Hepatocellular carcinoma (HCC), which has a complex pathogenesis and poor prognosis, is one of the most common malignancies worldwide. Hepatitis virus B infection is the most common cause of HCC in Asian patients. Autophagy is the process of digestion and degradation, and studies have shown that autophagy-associated effects are closely related to the development of HCC. In this study, we aimed to construct a prognostic model based on autophagy-related genes (ARGs) for the Asian HCC population to provide new ideas for the clinical management of HCC in the Asian population. METHODS: The clinical information and transcriptome data of Asian patients with HCC were downloaded from The Cancer Genome Atlas (TCGA) database, and 206 ARGs were downloaded from the human autophagy database (HADB). We performed differential and Cox regression analyses to construct a risk score model. The accuracy of the model was validated by using the Kaplan-Meier (K-M) survival curve, receiver operating characteristic (ROC) curve, and univariate and multivariate Cox independent prognostic analyses. The results Thirteen ARGs that were significantly associated with prognosis were finally identified by univariate and multivariate Cox regression analyses. The K-M survival curves showed that the survival rate of the low-risk group was significantly higher than that of the high-risk group (p < 0.001), and the multi-indicator ROC curves further demonstrated the predictive ability of the model (AUC = 0.877). CONCLUSION: The risk score model based on ARGs was effective in predicting the prognosis of Asian patients with HCC.

Plasma metabolomics for the assessment of the progression of non-small cell lung cancer.

OBJECTIVES: Non-small cell lung cancer (NSCLC) is a leading type of lung cancer with a high mortality rate worldwide. Although many procedures for the diagnosis and prognosis assessment of lung cancer exist, they are often laborious, expensive, and invasive. This study aimed to develop an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based analysis method for the plasma biomarkers of NSCLC with the potential to indicate the stages and progression of this malignancy conveniently and reliably. METHODS: A total of 53 patients with NSCLC in early stages (I-III) and advanced stage (IV) were classified into the early and advanced groups based on the tumor node metastasis staging system. A comprehensive metabolomic analysis of plasma from patients with NSCLC was performed via UPLC-MS/MS. Principal component analysis and partial least squares-discriminant analysis were conducted for statistical analysis. Potential biomarkers were evaluated and screened through receiver operating characteristic analyses and correlation analysis. Main differential metabolic pathways were also identified by utilizing metaboanalyst. RESULTS: A total of 129 differential metabolites were detected in accordance with the criteria of VIP ≥ 1 and a P-value of ≤ 0.05. The receiver operating characteristic curves indicated that 11 of these metabolites have the potential to be promising markers of disease progression. Apparent correlated metabolites were also filtered out. Furthermore, the 11 most predominant metabolic pathways with alterations involved in NSCLC were identified. CONCLUSION: Our study focused on the plasma metabolomic changes in patients with NSCLC. These changes may be used for the prediction of the stage and progression of NSCLC. Moreover, we discussed the metabolic pathways wherein the altered metabolites were mainly enriched.

Car accident as a trigger for reverse takotsubo-like cardiomyopathy with paraganglioma: Case report and literature review.

Paraganglioma (PGL), which may cause acute Takotsubo-like cardiomyopathy (TLC), is a rare neuroendocrine neoplasm derived from various body sites. TLC has been associated with excessive catecholamine secretion and shares the same cardiac presentation with Takotsubo cardiomyopathy (TTC). We present the case of a 58-year-old male who arrived at the hospital after a car accident, reporting symptoms of chest tightness, shortness of breath, and abdominal pain after a car accident. The patient was found to have elevated troponin and severely depressed left ventricular function. Echocardiography depicted a normal contracting apex with the rest of the left ventricle being hypokinetic. Coronary computed tomography (CT) angiogram revealed mild coronary artery disease. Abdominal CT further revealed a mass on the left side of the epigastric aorta, confirmed by autopsy as a PGL.

Insight into the Influence of the Graphite Layer and Cobalt Crystalline on a ZIF-67-Derived Catalyst for Fischer-Tropsch Synthesis.

Due to the special framework structure, ZIF-67 is a promising material as the precursor to prepare the Co@C catalysts with high cobalt loading and superior cobalt dispersion. Unfortunately, these Co@C-X catalysts exhibit not only unsatisfied activity but also high CH4 selectivity. This limited its further application due to the lack of in-depth analysis of the reasons behind it. In this work, the Co@C-X catalysts were prepared by pyrolyzing the ZIF-67 precursor at different temperatures. A series of characterizations were conducted to explore the behavior of the graphite carbon coated on cobalt species, realizing that the role of active Co sites on these Co@C catalysts was restricted by the graphite carbon layer since it suppressed the adsorption and activation of syngas on Co sites. TEOS was introduced to suppress the aggregation of cobalt species and more active sites were exposed after the graphite carbon layer was eliminated. As a result, the FTS performance was greatly improved by a factor of 5. The effect of O2 concentration on the microcrystalline size of Co and the reconfinement effect of SiO2 were investigated. The model catalyst was prepared and the key factors determining CH4 selectivity of the ZIF-67-derived Co@C catalyst were revealed. This provides a good basis for rational designing ZIF-67-derived Co-based FTS catalysts.

Progressive Folding and Adaptive Multivalent Recognition of Alkyl Amines and Amino Acids in p-Sulfonatocalix[4]arene Hosts: Solid-State and Solution Studies.

Invited for this month's cover is the group of Dr. Mihail Barboiu from the Institut Europeen des Membranes of Montpellier, France and the Lehn Institute of Functional Materials at Sun-yat Sen University in Guangzhou, China. The cover picture shows the molecular recognition of folded 1,ω-amino-acids guests within p-sulfonatocalix[4]arene host anions stabilized with alternating hydrated cations and water molecules. Read the full text of the article at 10.1002/cplu.202000232.

Progressive Folding and Adaptive Multivalent Recognition of Alkyl Amines and Amino Acids in p-Sulfonatocalix[4]arene Hosts: Solid-State and Solution Studies.

Calix[4]arenes have the ability to encapsulate biomimetic guests, offering interesting opportunities to explore their molecular recognition, very close to biological scenarios. In this study, p-sulfonatocalix[4]arene (C4 A) anions and hydrated alkali cations have been used for the in situ recognition of cationic 1,ω-diammonium-alkanes and 1,ω-amino-acids of variable lengths. NMR spectroscopy illustrates that these systems are stable in aqueous solution and the interaction process involves several binding states or stabilized conformations within the C4 A anion, depending of the nature of the guest. DOSY experiments showed that monomeric 1 : 1 host-guest species are present, while the cation does not influence their self-assembly in solution. The folded conformations observed in the solid-state X-ray single-crystal structures shed light on the constitutional adaptivity of flexible chains to environmental factors. Futhermore, a comprehensive screening of 30 single crystal structures helped to understand the in situ conformational fixation and accurate determination of the folded structures of the confined guest molecules, with a compression up to 40 % compared with their linear conformations.

"Calix[4]-box" cages promote the formation of amide bonds in water in the absence of coupling reagents.

The present work shows that encapsulation can be used to promote amide bond formation in water under mild conditions, in the absence of carbodiimide coupling agents.