Personalized drug screening in patient-derived organoids of biliary tract cancer and its clinical application.

Patients with biliary tract cancer (BTC) show different responses to chemotherapy, and there is no effective way to predict chemotherapeutic response. We have generated 61 BTC patient-derived organoids (PDOs) from 82 tumors (74.4%) that show similar histological and genetic characteristics to the corresponding primary BTC tissues. BTC tumor tissues with enhanced stemness- and proliferation-related gene expression by RNA sequencing can more easily form organoids. As expected, BTC PDOs show different responses to the chemotherapies of gemcitabine, cisplatin, 5-fluoruracil, oxaliplatin, etc. The drug screening results in PDOs are further validated in PDO-based xenografts and confirmed in 92.3% (12/13) of BTC patients with actual clinical response. Moreover, we have identified gene expression signatures of BTC PDOs with different drug responses and established gene expression panels to predict chemotherapy response in BTC patients. In conclusion, BTC PDO is a promising precision medicine tool for anti-cancer therapy in BTC patients.

Polyphenol-fortified extruded sweet potato starch vermicelli: Slow-releasing polyphenols is the main factor that reduces the starch digestibility.

To investigate the digestive behavior of extruded starch-polyphenols system, extruded sweet potato starch vermicelli (ESPSV) was used as a model. The multi-scale structure, starch digestibility, polyphenol release, digestive enzyme activity during digestion and their correlation of ESPSV supplemented with matcha (MT), green tea extract (GTE), tea polyphenols (TP) and epigallocatechin gallate (EGCG) (at 1% polyphenol level) were discussed. Results showed that tea products in whatever form could retard starch digestion, with EGCG working best. The predicted glycemic index (pGI) of ESPSV was decreased from 82.50 to 65.46 after adding EGCG. Starch formed larger molecular aggregates with tea products under extrusion, showing a "B + V" type pattern. The order of V-type crystals content was EGCG + ESPSV (1.41) > TP + ESPSV (1.50) > GTE + ESPSV (1.88) > MT + ESPSV (2.62) > ESPSV (3.20). Under external pressure, EGCG, as tea monomer, was more likely to enter the spiral cavity of amylose and form V-type inclusion complex. Notably, polyphenols released during digestion could still reduce digestive enzyme activity, with a 15.53% decrease in EGCG + ESPSV compared to ESPSV. This was verified by correlation analysis, where RDS content (0.961, p < 0.01) and pGI (0.966, p < 0.01) were highly significantly correlated with the enzyme activity. Furthermore, tea products did not break or even enhance the quality of ESPSV as the final product.

Effects of tea products on in vitro starch digestibility and eating quality of cooked rice using domestic cooking method.

Cooked rice (CR) is a staple diet for many people, but exhibits the high glycemic index that makes it difficult to control the blood glucose. Herein, instant green tea (IGT), instant black tea (IBT) and matcha (Mat) (1, 2 and 3% w/w, rice basis) were added to lower the in vitro starch digestibility and improve the eating quality of CR prepared with an electric rice cooker. The results showed that adding tea products at each level could remarkably reduce the in vitro starch digestibility of CR. Compared with IGT and IBT, 3% of Mat significantly decreased the contents of rapidly digestible starch (RDS) from 72.96% to 60.99%, the digestion rate constant (K) from 11.4 × 10-2 to 8.68 × 10-2 min-1 and the expected glycemic index (eGI) from 77.55 to 66.86. Furthermore, the gas chromatography-ion migration spectrum was analysed to confirm that the tea products endowed the cooked rice with a refreshing flavor by inducing the redistribution of the main aroma components. Moreover, it was found that increasing the ordered crystal structure of rice grains played a major role on lowering the starch digestion, which was demonstrated by the results of the Rapid Visco Analyser, scanning electron microscopy, X-ray diffraction and Fourier transform infrared spectroscopy. These findings suggested that cooking rice with tea products, especially Mat, can be useful in enhancing the palatability and slowing the in vitro digestion properties of CR.

Hypothalamic-Pituitary-Thyroid Axis Crosstalk With the Hypothalamic-Pituitary-Gonadal Axis and Metabolic Regulation in the Eurasian Tree Sparrow During Mating and Non-mating Periods.

Reproduction is an energetically costly phenomenon. Therefore, to optimize reproductive success, male birds invest enough energetic resources for maintaining well-developed testes. The hypothalamic-pituitary-thyroid (HPT) axis in birds can crosstalk with the hypothalamic-pituitary-gonadal (HPG) axis, thus orchestrating both the reproduction and metabolism. However, until now, how the free-living birds timely optimize both the energy metabolism and reproduction via HPT-axis is not understood. To uncover this physiological mechanism, we investigated the relationships among body mass, testis size, plasma hormones including thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3), metabolites including glucose (Glu), triglyceride (TG), total cholesterol (TC), uric acid (UA), diencephalon mRNA expressions of type 2 (Dio2) and 3 (Dio3) iodothyronine deiodinase enzymes, thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), gonadotropin-releasing hormone I (GnRH-I), and gonadotropin-inhibitory hormone (GnIH) in a male Eurasian tree sparrow (ETS, Passer montanus). We found significantly larger testis size; elevated diencephalon Dio2 and TRH mRNA expressions, plasma T3, and UA levels; and significantly lowered Glu, TG, and TC levels during mating relative to the non-mating stages in male ETSs. However, Dio3, TSH, GnRH-I, and GnIH mRNA expression did not vary with the stage. Furthermore, life-history stage dependent variation in plasma T3 had both direct effects on the available energy substrates and indirect effects on body mass and testis size, indicating a complex regulation of metabolic pathways through the HPT- and HPG-axes. The identified differences and relationships in mRNA expression, plasma T3 and metabolites, and testis size in male ETSs contribute to our understanding how free-living birds adjust their molecular, endocrinal, and biochemical features to orchestrate their reproductive physiology and metabolism for the maintenance of well-developed testes.

Chlorogenic acid and caffeine in combination inhibit fat accumulation by regulating hepatic lipid metabolism-related enzymes in mice.

Obesity has become a public health concern due to its positive association with the incidence of many diseases, and coffee components including chlorogenic acid (CGA) and caffeine have been demonstrated to play roles in the suppression of fat accumulation. To investigate the mechanism by which CGA and caffeine regulate lipid metabolism, in the present study, forty mice were randomly assigned to four groups and fed diets containing no CGA or caffeine, CGA, caffeine, or CGA+caffeine for 24 weeks. Body weight, intraperitoneal adipose tissue (IPAT) weight, and serum biochemical parameters were measured, and the activities and mRNA and protein expression of lipid metabolism-related enzymes were analysed. There was a decrease in the body weight and IPAT weight of mice fed the CGA+caffeine diet. There was a significant decrease in the serum and hepatic concentrations of total cholesterol, TAG and leptin of mice fed the CGA+caffeine diet. The activities of carnitine acyltransferase (CAT) and acyl-CoA oxidase (ACO) were increased in mice fed the caffeine and CGA+caffeine diets, while the activity of fatty acid synthase (FAS) was suppressed in those fed the CGA+caffeine diet. The mRNA expression levels of AMP-activated protein kinase (AMPK), CAT and ACO were considerably up-regulated in mice fed the CGA+caffeine diet, while those of PPARγ2 were down-regulated. The protein expression levels of AMPK were increased and those of FAS were decreased in mice fed the CGA+caffeine diet. These results indicate that CGA+caffeine suppresses fat accumulation and body weight gain by regulating the activities and mRNA and protein expression levels of hepatic lipid metabolism-related enzymes and that these effects are stronger than those exerted by CGA and caffeine individually.

Neuroanatomical differences between familial and sporadic schizophrenia and their parents: an optimized voxel-based morphometry study.

Symptomatic differences have been reported between patients with familial and sporadic schizophrenia. The present study examined neuroanatomical differences between the two subgroups and their parents using voxel-based morphometry. High-resolution T1-weighted images were obtained using 3 Tesla magnetic resonance imaging from 20 patients with schizophrenia (familial subgroup, n=10; sporadic subgroup, n=10), 20 of their parents (familial subgroup, n=10; sporadic subgroup, n=10) and 20 healthy volunteers. Gray matter density (GMD) was compared between groups on a voxel-by-voxel basis. Compared with the sporadic patients, the familial patients had significantly reduced GMD in the thalamus bilaterally. Reduction of GMD in bilateral thalami was also found in familial parents in comparison with sporadic parents. Compared with controls, both familial and sporadic patients had lower GMD involving bilateral insula, right temporal lobe, right occipital lobe, left lenticular nucleus and right cerebellum. However, only familial patients showed lower GMD than controls in the right thalamus. Compared with controls, only familial parents showed lower GMD in the right insula extending to the right temporal lobe and the right parietal lobule. The present data suggest that familial schizophrenia is associated with more severe structural abnormalities than sporadic schizophrenia, especially in the thalamus.

Adjuvant intraportal venous chemotherapy for patients with hepatocellular carcinoma and portal vein tumor thrombi following hepatectomy plus portal thrombectomy.

BACKGROUND: The aim of this study was to evaluate the clinical value of adjuvant chemobiotherapy via portal vein for patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombi (PVTT) following hepatectomy plus thrombectomy. METHODS: Eighty-six HCC patients with tumor thrombi in the portal trunk and/or the first-order branch were divided into groups A (n = 33) and B (n = 53). Patients in group A were treated with hepatectomy plus portal thrombectomy in combination with postoperative adjuvant chemobiotherapy administered via portal vein. The chemobiotherapy regimen consisted of 5-FU, adriamycin, cisplatin, and IFNalpha. Patients in Group B were subjected to hepatectomy plus thrombectomy alone. Survival rates of the two groups were compared and prognostic factors were identified using Cox proportional hazards model. RESULTS: Group A had a significantly longer median tumor-free survival time and median survival time compared with group B, i.e., 5.1 vs. 2.5 months (p = 0.017) and 11.5 vs. 6.2 months (p = 0.007), respectively. One-, two-, and three-year tumor-free survival rates were remarkably higher in group A than in group B, i.e., 18.4% vs. 8.4%, 13.8% vs. 4.2%, and 9.2% vs. 4.2%, respectively. One-, two-, and three-year survival rates were markedly greater in group A than in group B, i.e., 46.8% vs. 23.4%, 14.4% vs. 5.8%, and 9.6% vs. 5.8%, respectively. Multivariate analysis using the Cox proportional hazards model revealed that adjuvant chemobiotherapy, pathologic grading, and tumor size were independent prognostic factors for survival time (p = 0.000, 0.001, and 0.013, respectively), and chemobiotherapy and pathologic grading were independent prognostic factors for tumor-free survival time (p = 0.002 and 0.003, respectively). CONCLUSIONS: Surgical resection combined with adjuvant chemobiotherapy via portal vein is an effective and safe treatment modality for hepatocellular carcinoma with major portal vein thrombus.

[Surgical resection versus percutaneous thermal ablation for early-stage hepatocellular carcinoma: a randomized clinical trial].

OBJECTIVE: To compare the clinical results of surgical resection (SR) and percutaneous thermal ablation (PTA) for early-stage hepatocellular carcinoma (HCC) (single tumor nodule

[Role of arsenolite on 8-isoprostane of asthmatic mice plasm].

OBJECTIVE: Through the establishment of mouse' ovalbumin- sensitized asthmatic model and the observation of the 8-Isoprostane of plasm, to evaluate the therapeutic effects of arsenolite on asthmatic mice. METHOD: Forty-two healthy Kunming male mice were randomly divided into control group and experience groups, the latter were treated with dexamethasone, arsenolite. Lung function were tested, 8-isoprostane of plasm and WBC of BALF were measured. RESULT: Lung function improved after treating with dexamethasone or arsenolite. The WBC of asthmatic mice were significantly higher than those in control group, and decreased after treating with dexamethasone or arsenolite; 8-Isoprostane of plasm in asthmatic mice was higher than that of control group, and decreased after treating with dexamethasone or arsenolite. CONCLUSION: There is oxidant stress status in asthmatic mice. Arsenolite could lighten airway obstruction, reduce airway high response and redress oxidant stress status in asthmatic mice.