A Multiparametric MRI-based Radiomics Model for Stratifying Postoperative Recurrence in Luminal B Breast Cancer.

This study aims to develop an MRI-based radiomics model to assess the likelihood of recurrence in luminal B breast cancer. The study analyzed medical images and clinical data from 244 patients with luminal B breast cancer. Of 244 patients, 35 had experienced recurrence and 209 had not. The patients were randomly divided into the training set (51.5 ± 12.5 years old; n = 171) and the test set (51.7 ± 11.3 years old; n = 73) in a ratio of 7:3. The study employed univariate and multivariate Cox regression along with the least absolute shrinkage and selection operator (LASSO) regression methods to select radiomics features and calculate a risk score. A combined model was constructed by integrating the risk score with the clinical and pathological characteristics. The study identified two radiomics features (GLSZM and GLRLM) from DCE-MRI that were used to calculate a risk score. The AUCs were 0.860 and 0.868 in the training set and 0.816 and 0.714 in the testing set for 3- and 5-year recurrence risk, respectively. The combined model incorporating the risk score, pN, and endocrine therapy showed improved predictive power, with AUCs of 0.857 and 0.912 in the training set and 0.943 and 0.945 in the testing set for 3- and 5-year recurrence risk, respectively. The calibration curve of the combined model showed good consistency between predicted and measured values. Our study developed an MRI-based radiomics model that integrates clinical and radiomics features to assess the likelihood of recurrence in luminal B breast cancer. The model shows promise for improving clinical risk stratification and treatment decision-making.

A pH-Stable Tb-MOF as Luminescence Sensor for Highly Sensitive Detection of Amino Acids through Diverse Sensing Mechanism.

A luminescent Tb-MOF with excellent stability and dual-emitting properties was constructed with an amide-functionalized tetracarboxylate ligand. Tb-MOFs were initially assembled on one-dimensional Tb3+ chains, then formed a two-dimensional double-decker layer through the synergistic linking of organic ligands and bridging formic acid anions, and further fabricated the final three-dimensional structure through the connection of the organic ligands. Powder X-ray diffraction experiments revealed that Tb-MOFs not only exhibited excellent stability in water but also maintained structural integrity in the pH range of 2-12. Importantly, this Tb-MOF provided the first example of a metal-organic framework (MOF)-based luminescence sensor that can simultaneously detect two acid amino acids (aspartic and glutamic acids) through a turn-off sensing mechanism and two basic amino acids (lysine and arginine acids) through unusual turn-on and turn-off-on sensing mechanisms. Moreover, high sensitivity, low detection limit, and excellent recyclability of this sensor endow Tb-MOFs with great potential as a highly efficient amino acid fluorescence sensor in chemical detection and biological environments.

The improvement of intestinal dysbiosis and hepatic metabolic dysfunction in dextran sulfate sodium-induced colitis mice: effects of curcumin.

BACKGROUND AND AIM: Curcumin may have promising application in the prevention and amelioration of inflammatory bowel disease (IBD). However, the underlying mechanisms underpinning the ability of curcumin to interact with the gut and liver in IBD remains to be defined, which is the exploration aim of this study. METHODS: Mice with dextran sulfate sodium salt (DSS)-induced acute colitis were treated either with 100 mg/kg of curcumin or phosphate buffer saline (PBS). Hematoxylin-eosin (HE) staining, 16S rDNA Miseq sequencing, proton nuclear magnetic resonance (1 H NMR) spectroscopy, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were applied for analysis. Spearman's correlation coefficient (SCC) was utilized to assess the correlation between the modification of intestinal bacteria and hepatic metabolite parameters. RESULTS: Curcumin supplementation not only prevented further loss of body weight and colon length in IBD mice but also improved diseases activity index (DAI), colonic mucosal injury, and inflammatory infiltration. Meanwhile, curcumin restored the composition of the gut microbiota, significantly increased Akkermansia, Muribaculaceae_unclassified, and Muribaculum, and significantly elevated the concentration of propionate, butyrate, glycine, tryptophan, and betaine in the intestine. For hepatic metabolic disturbances, curcumin intervention altered 14 metabolites, including anthranilic acid and 8-amino-7-oxononanoate while enriching pathways related to the metabolism of bile acids, glucagon, amino acids, biotin, and butanoate. Furthermore, SCC analysis revealed a potential correlation between the upregulation of intestinal probiotics and alterations in liver metabolites. CONCLUSION: The therapeutic mechanism of curcumin against IBD mice occurs by improving intestinal dysbiosis and liver metabolism disorders, thus contributing to the stabilization of the gut-liver axis.

Electroacupuncture Attenuated Anxiety and Depression-Like Behavior via Inhibition of Hippocampal Inflammatory Response and Metabolic Disorders in TNBS-Induced IBD Rats.

This study was designed to explore the potential mechanisms of electroacupuncture (EA) in treating inflammatory bowel disease- (IBD-) related anxiety and mood disorders. A colitis model was induced in rats with 2, 4, 6-trinitrohydrosulfonic acid (TNBS), followed by ST36 and SP6 targeted therapy by EA or sham EA treatment. The elevated plus maze (EPM) and open-field test (OFT) were performed to assess the state of anxiety and depression-like behavior. Tests were carried out by 16S rDNA amplification sequence, 1H nuclear magnetic resonance (1H NMR) spectroscopy, immunofluorescence staining, and enzyme-linked immunosorbent assay (ELISA). The analyses detailed metabolic alterations and the Toll-like receptor 4 (TLR4) signaling pathway/NOD-like receptor protein 3 (NLRP3) inflammasome in rats' hippocampal region. Furthermore, the activity of the hypothalamic-pituitary adrenal (HPA) axis and gut microbiome was assessed. As a result of treatment, EA significantly improved in the behavioral tests and altered the composition of the gut microbiome through a significant increase in the density of short chain fatty acids (SCFAs) producers mainly including Ruminococcaceae, Phascolarctobacterium, and Akkermansiaceae. EA upregulated the metabolites of the hippocampus mainly containing l-glutamine and gamma-aminobutyric acid (GABA), as well as ZO-1 expression. Whereas the treatment blocked the TLR4/nuclear factor- kappa B (NF-κB) signaling pathways and NLRP3 inflammasomes, along with downregulating the interleukin- (IL-) 1ß level. The hyperactivity of the HPA axis was also diminished. In conclusion, EA at ST36 and SP6 attenuated anxiety and depression-like behavior in colitis model rats through their effects on the gut microbiome by modulating the hippocampal inflammatory response and metabolic disorders, as well as the HPA axis. This study provides evidence for clinical application of EA to serve as an adjunctive treatment for IBD-related anxiety and depression.

Efficacy of exenatide on weight loss, metabolic parameters and pregnancy in overweight/obese polycystic ovary syndrome.

CONTEXT: Weight loss remains one of the most important arms in obese patients with polycystic ovary syndrome (PCOS). Further studies are needed to identify the best treatment. OBJECTIVE: To evaluate the effects of exenatide (EXE) on reproductive and metabolic function in overweight/obese (OW/OB) PCOS. DESIGN: This is a 24-week open-label prospective, randomized, clinical study. PATIENTS AND MEASUREMENTS: This study randomized 176 OW/OB women diagnosed with PCOS to receive either EXE 10 µg BID (n = 88) or metformin (MET) 1000 mg BID (n = 88) for the first 12 weeks. Then all patients were treated with MET alone during the second 12 weeks. We observed metabolic parameters at 0 and 12 weeks, and then tracked the rate of pregnancy during the second 12 weeks. RESULTS: After the first 12 weeks of intervention, compared with MET, subjects who received EXE had significantly decreased weight (4.29 ± 1.29 kg vs 2.28 ± 0.55 kg, P < .001) and total fat% (4.67 ± 0.09% vs 1.11 ± 0.32%, P < .001), improved the homeostasis model of assessment for insulin resistance (1.30 ± 0.58 vs 0.59 ± 0.12, P < .001) and increased the menstrual frequency ratio (0.62 ± 0.12 vs 0.37 ± 0.01, P < .001). During the second 12 weeks, the rate of natural pregnancy of EXE-treated patients was significantly higher than MET-treated patients (43.60% vs 18.70%, P < .05). CONCLUSIONS: Short-term EXE therapy was linked to significant weight loss and central adiposity reduction, which may further explain the improvements in insulin resistance, inflammatory marker and menstrual cycle, which may contribute to increasing pregnancy rates in OW/OB women with PCOS.

Lambda-carrageenan oligosaccharides elicit reactive oxygen species production resulting in mitochondrial-dependent apoptosis in human umbilical vein endothelial cells.

Previous studies have shown that highly sulfated lambda-carrageenan oligosaccharides (lambda-CO) possess an anti-angiogenetic effect, while high concentrations of lambda-CO present a cytotoxic effect towards human umbilical vein endothelial cells (HUVECs). The aim of this study was to explore the underlying mechanism of lambda-CO on inhibiting cell proliferation. lambda-CO elicited reactive oxygen species (ROS) production with concentrations at 0.8 and 1 mg/ml, and this event was accompanied by the increase of early apoptotic cells, nuclear morphology changes and cell cycle arrest at the S and G2/M phases. However, prevention of oxidative stress by N-acetyl-L-cysteine (NAC) could abolish the effect of lambda-CO on these events. Yet, lambda-CO induced a depolarization of mitochondrial transmembrane potential. At 0.8 mg/ml, lambda-CO induced up-regulation of p53 and Bax, down-regulation of Bcl-2 and activation of caspase-9 and -3. These results suggest that exposure to a high concentration of lambda-CO activates the mitochondrial-mediated apoptotic pathway and cell cycle arrest by generation of ROS.

Complete profiling and characterization of in vitro nefazodone metabolites using two different tandem mass spectrometric platforms.

This paper describes the complete profiling and characterization of in vitro metabolites of the antidepressant agent nefazodone (NEF) generated by human liver microsome (HLM). Two new metabolic pathways (biotransformation) for NEF have been discovered by the characterization of three new metabolites, including two new metabolites (M24, M25) formed due to the N-dealkylation reaction that occurred between the triazolone and propyl units, and one new metabolite (M26) formed due to the O-dearylation reaction that occurred on the phenoxyethyl unit. These metabolites were initially detected by a 4000 Q-Trap instrument and then confirmed by exact mass measurement using an LTQ-Orbitrap. Both instruments proved to be capable of providing complete in vitro metabolite information in a single liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis, although each had its advantages and disadvantages. One noticeable disadvantage of the 4000 Q-Trap was the reduced quality of isotopic pattern in the enhanced mass scan (EMS) spectrum when it was used as survey scan to trigger multiple dependent product ion scans. The problem was especially exacerbated for minor metabolites with low signal intensity. On the other hand, the LTQ-Orbitrap maintained excellent isotopic pattern when used as a full scan survey scan. Twenty-six metabolites were detected and identified. The formation of these new metabolites was also confirmed by analyzing duplicate incubations at different time points.