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Curcumin and exercise have been reported to show good anti-tumour effects. However, relevant research on the combined effects of physical exercise and curcumin supplementation on cancer and the underlying mechanisms is still lacking. The current study aimed to construct an anti-breast tumour mouse model using the combined effects of curcumin treatment and swimming exercise. Transcriptomic and metabolomic techniques were used to screen for differentially expressed genes and metabolites, evaluate the anticancer effects, and analyse the molecular regulatory mechanisms related to metabolism. Observation of the mouse phenotypes, including tumour appearance, in-vivo tumour imaging, and HE staining results of pathological sections, suggested a more obvious inhibitory effect of the combination of curcumin administration and exercise intervention on breast cancer than that of a single treatment. The combination treatment group had a total of 445 differentially expressed (154 upregulated and 291 downregulated) genes. Functional enrichment analysis showed the calcium signalling pathway, Wnt signalling pathway, PI3K Akt signalling pathway, and IL-17 signalling pathway to significantly participate in the anti-breast cancer process of curcumin-exercise combination treatment. Results of the intergroup differential metabolite analysis showed that the combined effect of curcumin and exercise involves two unique pathways, namely the amino sugar and nucleotide sugar metabolism, which includes chitosan, d-glucosamine 6-phosphate, l-fucose, and N-acetyl beta-mannosamine, and the amino acid biosynthesis, which includes dl-isoleucine, dl-tyrosine, and homocysteine. Collectively, the top-ranked genes and metabolites with the highest degree of associations were further revealed by O2PLS analysis. Overall, the study helped reveal the mechanism of action of curcumin-exercise combination treatment on breast cancer at multi-omics level.

The therapeutic mechanism of oleanolic acid (OA) in breast cancer has been widely reported, but little has been known about the combined effects of transcriptome and gut microbiome. In this study, the phenotypic effect of oleanolic acid on mice was tested at the end of the administration cycle, and RNA sequencing on murine tumor tissue and 16S-rRNA sequencing on intestinal contents were conducted to analyze gene expression profiles and microbial diversity between the control group and OA treated group using 4T1-induced mice breast cancer model. As a result, it has been confirmed that oleanolic acid would play a significant inhibitory effect on the development of breast tumors in mice. Based on the integrative analysis of the transcriptomic and metagenomic data, it was found that the abundance of Lactobacillus in the intestinal flora of mice significantly increased in the OA group. Moreover, the up-regulation of Il10 had a significant effect on inhibiting the tumor progression, which played a role through cytokine-cytokine receptor interaction pathway.

We propose a quantification CνGn of n-mode Gaussian coherence. The value of CνGn only depends on the covariance matrices and displacement vectors of continuous-variable states without any optimization procedures, and thus is easily calculated. For n=1, CνG1 is a proper Gaussian coherence measure of single-mode CV system. For n≥2, CνGn is invariant under any permutation of submodes, nonincreasing under any n-mode local incoherent Gaussian channels, vanishes at incoherent Gaussian states, and, satisfies the unification condition and the hierarchy condition that a multi-partite quantum correlation measure should obey. Thus CνGn is a multi-partite Gaussian correlation measure, which reveals, though the quantum coherence lives in single-partite systems, that the multi-mode coherence for continuous-variable systems can be regarded as a multipartite Gaussian correlation between modes, and such multi-partite Gaussian correlation is also a quantum resource. Moreover, we show that CνGn is completely monogamous as a multipartite Gaussian correlation measure. This means that the n-mode Gaussian coherence subjects to the principles of resource allocation. In addition, CνGn is an upper bound of the geometric-based single-mode Gaussian coherence measure CBu by the Bures distance at pure Gaussian states of mode ≤2 and can be used to detect coherence in any n-mode Gaussian states more efficiently.

Patient-derived tumor xenografts (PDXs) are a powerful tool for drug discovery and screening in cancer. However, current studies have led to little understanding of genotype mismatches in PDXs, leading to massive economic losses. Here, we established PDX models from 53 lung cancer patients with a genotype matching rate of 79.2% (42/53). Furthermore, 17 clinicopathological features were examined and input in stepwise logistic regression (LR) models based on the lowest Akaike information criterion (AIC), least absolute shrinkage and selection operator (LASSO)-LR, support vector machine (SVM) recursive feature elimination (SVM-RFE), extreme gradient boosting (XGBoost), gradient boosting and categorical features (CatBoost), and the synthetic minority oversampling technique (SMOTE). Finally, the performance of all models was evaluated by the accuracy, area under the receiver operating characteristic curve (AUC), and F1 score in 100 testing groups. Two multivariable LR models revealed that age, number of driver gene mutations, epidermal growth factor receptor (EGFR) gene mutations, type of prior chemotherapy, prior tyrosine kinase inhibitor (TKI) therapy, and the source of the sample were powerful predictors. Moreover, CatBoost (mean accuracy = 0.960; mean AUC = 0.939; mean F1 score = 0.908) and the eight-feature SVM-RFE (mean accuracy = 0.950; mean AUC = 0.934; mean F1 score = 0.903) showed the best performance among the algorithms. Meanwhile, application of the SMOTE improved the predictive capability of most models, except CatBoost. Based on the SMOTE, the ensemble classifier of single models achieved the highest accuracy (mean = 0.975), AUC (mean = 0.949), and F1 score (mean = 0.938). In conclusion, we established an optimal predictive model to screen lung cancer patients for non-obese diabetic (NOD)/Shi-scid, interleukin-2 receptor (IL-2R) γnull (NOG)/PDX models and offer a general approach for building predictive models.

As part of the United States Pharmacopeia’s ongoing review of dietary supplement safety data, a new comprehensive systematic review on green tea extracts (GTE) has been completed. GTEs may contain hepatotoxic solvent residues, pesticide residues, pyrrolizidine alkaloids and elemental impurities, but no evidence of their involvement in GTE-induced liver injury was found during this review. GTE catechin profiles vary significantly with manufacturing processes. Animal and human data indicate that repeated oral administration of bolus doses of GTE during fasting significantly increases bioavailability of catechins, specifically EGCG, possibly involving saturation of first-pass elimination mechanisms. Toxicological studies show a hepatocellular pattern of liver injury. Published adverse event case reports associate hepatotoxicity with EGCG intake amounts from 140 mg to ∼1000 mg/day and substantial inter-individual variability in susceptibility, possibly due to genetic factors. Based on these findings, USP included a cautionary labeling requirement in its Powdered Decaffeinated Green Tea Extract monograph that reads as follows: “Do not take on an empty stomach. Take with food. Do not use if you have a liver problem and discontinue use and consult a healthcare practitioner if you develop symptoms of liver trouble, such as abdominal pain, dark urine, or jaundice (yellowing of the skin or eyes).”

Ovalbumin (OVA) is one of the major allergenic proteins in egg that contain numerous functional properties. Here, oxidation-induced changes to the structure, functional properties, and allergenicity of OVA were evaluated after 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH) and acrolein treatment. Oxidation complexes were prepared by the lipid peroxidation, which caused structural changes, and increased digestibility, foaming, and emulsifying properties. The IgE-binding capacity of OVA decreased after oxidation. KU812 cell assay showed that the histamine and IL-4 levels decreased upon oxidation with AAPH and acrolein. A mouse model study showed that oxidation caused a reduction in the allergenicity by reducing IgE and IgG1 levels and the production of Th2 cytokines after acrolein (1 mmol/L) and AAPH (5 mmol/L) treatment. Thus, OVA could cause changes to structural and functional properties, modulating Th1/Th2 immunobalance, and reducing potential allergenicity after oxidation by lipid peroxidation, which might provide an effective and potential method to process hypoallergenic OVA.

Background: Diabetes is a complex and widespread disease, and type 2 diabetes mellitus (T2DM) diagnoses continue to climb throughout the world. Traditional herbal medicine is used for many health conditions, and Momordica charantia is the most commonly used plant around the world in treating diabetes. Hypothesis: We hypothesized that the well-established hypoglycemic activity of M. charantia is due to the saponin-induced stimulation of insulin secretion, resulting in normalization of glucose metabolism. In addition, we investigate whether saponins support the proliferation of pancreatic β-cells.Study Design and Methods: To test this, C57BLK/6 mice were fed a low or high fat diet. Either a crude extract or saponin rich fraction (SRF) of M. charantia or vehicle was orally administered daily for 4 weeks. Results: The SRF lowered fasting glucose concentrations, and both the crude extract and SRF improved glucose tolerance. The SRF did not impact β-cell mass, when compared to other treatment groups. Conclusions: In conclusion, our study suggests that saponins are responsible for all, or part, of the hypoglycemic effect and insulin secretory activity reported in M. charantia fruit.

Enhanced activity of the glutamatergic system has been linked to migraine pathophysiology. The present study aimed to assess the involvement of the glutamatergic system in the onset of attacks. We provoked attacks by infusion of glyceryl trinitrate (GTN; 0.5 µg/kg/min over 20 min) in 24 female episodic migraineurs without aura and 13 female age-matched healthy controls. Over the course of a single day participants were scanned three times at fixed time slots (baseline before GTN infusion, 90 min and 270 min after start of GTN infusion). Single-volume proton magnetic resonance spectra ( 1 H-MRS) were acquired at 7 Tesla from a volume of interest (VOI, 2x2x3 cm) in the visual cortex. We assessed the concentrations of glutamate, its major precursor glutamine, and its product gamma-aminobutyric acid (GABA) over the course of a provoked attack. The preictal state was defined as the period after GTN infusion until the migraine-like headache started, independent of possible experienced premonitory symptoms, and the ictal state was defined as the period with provoked migraine-like headache. Data were analyzed using a linear mixed-effect model for repeated measures. Glutamate and glutamine levels did not change from interictal to the preictal and ictal state. GABA levels increased from interictal towards the preictal state for migraine patients compared with healthy controls. We conclude that high resolution 7T MRS is able to show changes in the glutamatergic system towards a triggered migraine attack, by revealing an increased GABA concentration associated with the onset of a migraine attack., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aims: Several studies have shown that glucagon-like peptide-1 (GLP-1) analogues can affect resting energy expenditure, and preclinical studies suggest that they may activate brown adipose tissue (BAT). The aim of the present study was to investigate the effect of treatment with liraglutide on energy metabolism and BAT fat fraction in patients with type 2 diabetes., Methods and Results: In a 26-week double-blind, placebo-controlled trial, 50 patients with type 2 diabetes were randomized to treatment with liraglutide (1.8 mg/day) or placebo added to standard care. At baseline and after treatment for 4, 12 and 26 weeks, we assessed resting energy expenditure (REE) by indirect calorimetry. Furthermore, at baseline and after 26 weeks, we determined the fat fraction in the supraclavicular BAT depot using chemical-shift water-fat MRI at 3T. Liraglutide reduced REE after 4 weeks, which persisted after 12 weeks and tended to be present after 26 weeks (week 26 vs baseline: liraglutide -52 ± 128 kcal/day; P = 0.071, placebo +44 ± 144 kcal/day; P = 0.153, between group P = 0.057). Treatment with liraglutide for 26 weeks did not decrease the fat fraction in supraclavicular BAT (-0.4 ± 1.7%; P = 0.447) compared to placebo (-0.4 ± 1.4%; P = 0.420; between group P = 0.911)., Conclusion: Treatment with liraglutide decreases REE in the first 12 weeks and tends to decrease this after 26 weeks without affecting the fat fraction in the supraclavicular BAT depot. These findings suggest reduction in energy intake rather than an increase in REE to contribute to the liraglutide-induced weight loss., Trial Registry Number: NCT01761318., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest associated with this manuscript., (Copyright © 2020 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Assessment of muscle atrophy and fatty degeneration in brachial plexus injury (BPI) could yield valuable insight into pathophysiology and could be used to predict clinical outcome. The objective of this study was to quantify and relate fat percentage and cross-sectional area (CSA) of the biceps to range of motion and muscle force of traumatic brachial plexus injury (BPI) patients., Methods: T1-weighted TSE sequence and three-point Dixon images of the affected and non-affected biceps brachii were acquired on a 3 Tesla magnetic resonance scanner to determine the fat percentage, total and contractile CSA of 20 adult BPI patients. Regions of interest were drawn by two independent investigators to determine the inter-observer reliability. Paired Students' t-test and multivariate analysis were used to relate fat percentage, total and contractile CSA to active flexion and biceps muscle force., Results: The mean fat percentage 12±5.1% of affected biceps was higher than 6±1.0% of the non-affected biceps (p<0.001). The mean contractile CSA 8.1±5.1cm 2 of the affected biceps was lower than 19.4±4.9cm 2 of the non-affected biceps (p<0.001). The inter-observer reliability was excellent (ICC 0.82 to 0.96). The contractile CSA contributed most to the reduction in active flexion and muscle force., Conclusion: Quantitative measurement of fat percentage, total and contractile CSA using three-point Dixon sequences provides an excellent reliability and relates with active flexion and muscle force in BPI., (Copyright © 2016 Elsevier Inc. All rights reserved.)