p-Synephrine Indicates Internal Maturity of Citrus grandis (L.) Osbeck cv. Mato Peiyu-Reclaiming Functional Constituents from Nonedible Parts.

The processing of Citrus grandis Osbeck cv. Mato Peiyu (CGMP) fruits generates a considerable amount of waste, mainly the flavedo, albedo, and segment membrane; the generated waste yields severe environmental and economic challenges. In this study, we tried to reclaim some functional chemicals from the waste. Our data indicated that the essential oil content in the flavedo was 0.76-1.34%, with the major component being monoterpenes (93.75% in August, declining to 85.56% in November, including mainly limonene (87.08% to 81.12%) and others such as ß-myrcene). p-Synephrine (mg/100 g dry weight) declined accordingly (flavedo, 10.40 to 2.00; albedo, 1.80 to 0.25; segment membrane, 0.3 in August, 0.2 in September, and none since October). Polyphenols (in µg/g) included gallic acid (70.32-110.25, 99.27-252.89, and 105.78-187.36, respectively); protocatechuic acid (65.32-204.94, 26.35-72.35, and 214.98-302.65, respectively), p-coumaric acid (30.63-169.13, 4.32-17.00, and 6.68-34.32, respectively), ferulic acid (12.36-39.36, 1.21-10.25, and 17.07-39.63, respectively), and chlorogenic acid (59.19-199.36, 33.08-108.57, and 65.32-150.14, respectively). Flavonoids (in µg/g) included naringin (flavedo, 89.32-283.19), quercetin (181.05-248.51), nobiletin (259.75-563.7), hesperidin, and diosmin. The phytosterol content (mg/100 g) was 12.50-44.00 in the flavedo. The total dietary fiber in the segment membrane was 57 g/100 g. The antioxidant activity against the DPPH• and ABTS+• free radicals was moderately high. In conclusion, the waste of CGMP fruits is worth reclaiming for essential oil, p-synephrine, polyphenolics, and dietary fiber. Notably, p-synephrine content (flavedo: <8 mg/100 g dry weight, albedo: <2.0, or segment membrane: <0.4 mg) can serve as a marker of the internal maturation of CGMP fruits.

Inhibitory Effect of Styrylpyrone Extract of Phellinus linteus on Hepatic Steatosis in HepG2 Cells.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is estimated to be approximately about 25.24% of the population worldwide. NAFLD is a complex syndrome and is characterized by a simple benign hepatocyte steatosis to more severe steatohepatitis in the liver pathology. Phellinus linteus (PL) is traditionally used as a hepatoprotective supplement. Styrylpyrone-enriched extract (SPEE) obtained from the PL mycelia has been shown to have potential inhibition effects on high-fat- and high-fructose-diet-induced NAFLD. In the continuous study, we aimed to explore the inhibitory effects of SPEE on free fatty acid mixture O/P [oleic acid (OA): palmitic acid (PA); 2:1, molar ratio]-induced lipid accumulation in HepG2 cells. Results showed that SPEE presented the highest free radical scavenging ability on DPPH and ABTS, and reducing power on ferric ions, better than that of partitions obtained from n-hexane, n-butanol and distilled water. In free-fatty-acid-induced lipid accumulation in HepG2 cells, SPEE showed an inhibition effect on O/P-induced lipid accumulation of 27% at a dosage of 500 µg/mL. As compared to the O/P induction group, the antioxidant activities of superoxide dismutase, glutathione peroxidase and catalase were enhanced by 73%, 67% and 35%, respectively, in the SPEE group. In addition, the inflammatory factors (TNF-α, IL-6 and IL-1ß) were significantly down-regulated by the SPEE treatment. The expressions of anti-adipogenic genes involved in hepatic lipid metabolism of 5' adenosine monophosphate (AMP)-activated protein kinase (AMPK), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) were enhanced in the SPEE supplemented HepG2 cells. In the protein expression study, p-AMPK, SIRT1 and PGC1-α were significantly increased to 121, 72 and 62%, respectively, after the treatment of SPEE. Conclusively, the styrylpyrone-enriched extract SPEE can ameliorate lipid accumulation and decrease inflammation and oxidative stress through the activation of SIRT1/AMPK/PGC1-α pathways.

Molecular Action Mechanism of Coixol from Soft-Shelled Adlay on Tyrosinase: The Future of Cosmetics.

Coix lacryma-jobi var. ma-yuen L. Gramineae is widely cultivated in Taiwan. Literature regarding the molecular action mechanism of coixol on tyrosinase and the application of coicis seed extracts to the processing of facial masks is still lacking. Solvent extractability analysis revealed that most of the polyphenolics in coicis seeds were water soluble (3.17 ± 0.12 to 3.63 ± 0.07 µg/mLGAE). In contrast, the methanolic extract contained the most flavonoids (0.06 ± 0.00~0.26 ± 0.03 µg/mL QE) and coixol (11.43 ± 0.13~12.83 ± 0.14 µg/mL), showing potent antioxidant capability. Additionally, the contents of coixenolide (176.77 ± 5.91 to 238.60 ± 0.21 µg/g), phytosterol (52.45 ± 2.05 to 58.23 ± 1.14 mg/g), and polysaccharides (3.42 ± 0.10 to 4.41 ± 0.10 mg/g) were rather high. The aqueous extract (10 µg/mL) and the ethanolic extract (1 mg/mL) showed no cytotoxicity to B16F10 melanocytes. More attractively, the ethanolic extract at 1 mg/mL caused 48.4% inhibition of tyrosinase activity in B16F10 melanocytes, and 50.7% on human tyrosinase (hTyr) fragment 369-377. Conclusively, the coicis seed extracts containing abundant nutraceuticals with promising anti-hTyr activity and moisturizing capability can serve as good ingredients for facial mask processing.

Volatile Variation of Theobroma cacao Malvaceae L. Beans Cultivated in Taiwan Affected by Processing via Fermentation and Roasting.

After being harvested, cacao beans are usually subjected to very complex processes in order to improve their chemical and physical characteristics, like tastefulness with chocolate characteristic flavors. The traditional process consists of three major processing stages: fermentation, drying, and roasting, while most of the fermentation is carried out by an on-farm in-box process. In Taiwan, we have two major cocoa beans, the red and the yellow. We proposed that the major factor affecting the variation in tastes and colors in the finished cocoa might be the difference between cultivars. To uncover this, we examined the effect of the three major processes including fermentation, drying and roasting on these two cocoa beans. Results indicated that the two cultivars really behaved differently (despite before or after processing with fermentation, drying, and roasting) with respect to the patterns of fatty acids (palmitic, stearic, oleic, and arachidonic); triacylglycerols:1,2,3-trioleoyl-glycerol (OOO); 1-stearoyl-2,3-oleoyl-glycerol (SOO); 1-stearoyl-sn-2-oleoyl-3-arachidoyl- glycerol (SOA); 1,3-distearyol-sn-2-oleoyl-glycerol (SOS); organic acids (citric, tartaric, acetic, and malic); soluble sugars (glucose and fructose); amino acids; total phenolics; total flavonoids; and volatiles. Our findings suggest that to choose specific processing conditions for each specific cocoa genotype is the crucial point of processing cocoa with consistent taste and color.

Styrylpyrones from Phellinus linteus Mycelia Alleviate Non-Alcoholic Fatty Liver by Modulating Lipid and Glucose Metabolic Homeostasis in High-Fat and High-Fructose Diet-Fed Mice.

Phellinus linteus (PL), an edible and medicinal mushroom containing a diversity of styrylpyrone-type polyphenols, has been shown to have a broad spectrum of bioactivities. In this study, the submerged liquid culture in a 1600-L working volume of fermentor was used for the large-scale production of PL mycelia. Whether PL mycelia extract is effective against nonalcoholic fatty liver disease (NAFLD) is still unclear. In the high fat/high fructose diet (HFD)-induced NAFLD C57BL/6 mice study, the dietary supplementation of ethyl acetate fraction from PL mycelia (PL-EA) for four weeks significantly attenuated an increase in body weight, hepatic lipid accumulation and fasting glucose levels. Mechanistically, PL-EA markedly upregulated the pgc-1α, sirt1 genes and adiponectin, downregulated gck and srebp-1c; upregulated proteins PPARγ, pAMPK, and PGC-1α, and downregulated SREBP-1 and NF-κB in the liver of HFD-fed mice. Furthermore, the major purified compounds of hispidin and hypholomine B in PL-EA significantly reduced the level of oleic and palmitic acids (O/P)-induced lipid accumulation through the inhibition of up-regulated lipogenesis and the energy-metabolism related genes, ampk and pgc-1α, in the HepG2 cells. Consequently, these findings suggest that the application of PL-EA is deserving of further investigation for treating NAFLD.

Nutrient composition of Chenopodium formosanum Koidz. bran: Fractionation and bioactivity of its soluble active polysaccharides.

Background: Chenopodium formosanum Koidz. Amaranthaceae-also known as Djulis or red quinoa (RQ)-is a cereal plant indigenous to Taiwan, known for its high nutrient value. However, its bran is considered a waste product and the nutrient value has never been analyzed. Methods: In this study, we examined the proximate composition of RQ bran, specifically its soluble polysaccharide fractions. Results: RQ bran exhibited high contents of protein (16.56%), ash (7.10%), carbohydrate (60.45%), total polyphenolics (1.85%), betaxanthin (9.91 mg/100 g of RQ bran), and indicaxanthin (7.27 mg/100 g of RQ bran). Specifically, it was rich in polyunsaturated fatty acids (PUFAs; 39.24%)-with an n-6/n-3 and PUFA/saturated fatty acid (SFA) ratio of 18.137 and 0.743, respectively. Four soluble polysaccharide fractions were also obtained: CF-1, CF-2, CF-3, and CF-4, with yields of 3.90%, 6.74%, 22.28%, and 0.06%, respectively, and molecular weights of 32.54, 24.93, 72.39, and 55.45 kDa, respectively. CF-1, CF-2, CF-3, and CF-4 had respectively 15.67%, 42.41%, 5.44%, and 14.52% peptide moiety content and 38.92%, 50.70%, 93.76%, and 19.80% carbohydrate moiety. In CF-2, the glucose content was 95.86 mol% and that of leucine was 16.23%, implicating the presence of a typical leucinoglucan. All four polysaccharide fractions lacked glutamic acid and hydroxyproline. The IC50 of CF-1, CF-2, and CF-3 was respectively 12.05, 3.98, and 14.5 mg/mL for DPPH free radical-scavenging ability; 5.77, 4.10, and 7.03 mg/mL for hydrogen peroxide-scavenging capability; 0.26, 0.05, and 0.19 mg/mL for O2 - free radical-scavenging capability; and 100.41, 28.12, and 29.73 mg/mL for Fe2+ chelation. Conclusion: Our results indicated that RQ bran has a large amount of nutrient compounds, and a cost-efficient process for their extraction is needed. Their biomedical application as nutraceuticals also warrants further investigation.

High-Purity Preparation of Enzyme Transformed Trans-Crocetin Reclaimed from Gardenia Fruit Waste.

The recovery of physiologically bioactive ingredients from agricultural wastes as an abundant and low-cost source for the production of high value-added mutraceuticlas has been recognized and supported for the commercial interests and sustainable managements. In the extraction of geniposide for the development of natural food colorants from the dried fruits of Gardenia jasminoides Rubiaceae, the gardenia fruit waste (GFW) still remaining 0.86% (w/w) of crocins has always been discarded without any further treatments Until now, there was no simple and effective protocol for high-purity trans-crocein (TC) preparation without the coexistence of non-biologically active cis-crocein from GFW. We proposed an effective process to obtain the compound as follows. Crocins were extracted firstly by 50% of ethanol in the highest yield of 8.61 mg/g (w/w) from GFW. After the HPD-100 column fractionation in the collecting of crocins, the conversion ratio of 75% of crocins to crocetins can be obtained from the commercial available enzyme- Celluclast® 1.5 L. The crocins hydrolyzed products, were then separated through the HPD-100 resin adsorption and finally purified with the centrifugal partition chromatography (CPC) in single-step to obtain TC in a purity of 96.76 ± 0.17%. Conclusively, the effective enzyme transformation and purification co-operated with CPC technologies on crocins resulted in a high purity product of TC may be highly application in the commercial production.

Bicalutamide may enhance kidney injury in diabetes by concomitantly damaging energy production from OXPHOS and glycolysis.

Bicalutamide (Bic), frequently used in androgen-deprivation therapy for treating prostate cancer, was demonstrated to induce multiple apoptosis and fibrosis pathways and mitochondrial dysfunction in renal mesangial cells. Whether Bic also damages the glycolytic pathway has never been cited. To investigate this, we performed an in vitro model study with mesangial cells, and at the same time, collected data from an in vivo experiment. Bic induced hypoxia-inducible factor (HIF)-1 which upregulates phosphorylated-5'-AMP-activated protein kinase (p-AMPK) and severely suppresses the rate of adenosine triphosphate (ATP) production in both the oxidative phosphorylation and glycolysis pathways. Bic suppressed the oxygen consumption rate, extracellular acidification rate, and mitochondrial proton efflux rate, downregulated in vivo but upregulated in vitro glucose transporter (GLUT)-1, reduced glucose uptake, inhibited key glycolytic enzymes, including phosphofructokinase (PFK), pyruvate kinase (PK), and pyruvate dehydrogenase (PDH), and upregulated hexokinase II (HKII) and lactic dehydrogenase A (LDHA). In vivo, Bic downregulated renal cubilin levels, thereby disrupting the glomerular reabsorption function. Conclusively, Bic can damage bioenergenesis from both mitochondria and glycolysis. It was suggested that long-term administration of Bic can initiate renal damage depending on the duration and dose of treatment, which requires cautious follow-up.

Potential Protection Effect of ER Homeostasis of N6-(2-Hydroxyethyl)adenosine Isolated from Cordyceps cicadae in Nonsteroidal Anti-Inflammatory Drug-Stimulated Human Proximal Tubular Cells.

Nonsteroidal anti-inflammatory drugs (NSAIDs) belong to a class of universally and commonly used anti-inflammatory analgesics worldwide. A diversity of drawbacks of NSAIDs have been reported including cellular oxidative stress, which in turn triggers the accumulation of unfolded proteins, enhancing endoplasmic reticulum stress, and finally resulting in renal cell damage. Cordyceps cicadae (CC) has been used as a traditional medicine for improving renal function via its anti-inflammatory effects. N6-(2-hydroxyethyl)adenosine (HEA), a physiologically active compound, has been reported from CC mycelia (CCM) with anti-inflammatory effects. We hypothesize that HEA could protect human proximal tubular cells (HK-2) from NSAID-mediated effects on differential gene expression at the mRNA and protein levels. To verify this, we first isolated HEA from CCM using Sephadex® LH-20 column chromatography. The MTT assay revealed HEA to be nontoxic up to 100 µM toward HK-2 cells. The HK-2 cells were pretreated with HEA (10-20 µM) and then insulted with the NSAIDs diclofenac (DCF, 200 µM) and meloxicam (MXC, 400 µM) for 24 h. HEA (20 µM) effectively prevented ER stress by attenuating ROS production (p < 0.001) and gene expression of ATF-6, PERK, IRE1α, CDCFHOP, IL1ß, and NFκB within 24 h. Moreover, HEA reversed the increase of GRP78 and CHOP protein expression levels induced by DCF and MXC, and restored the ER homeostasis. These results demonstrated that HEA treatments effectively protect against DCF- and MXC-induced ER stress damage in human proximal tubular cells through regulation of the GRP78/ATF6/PERK/IRE1α/CHOP pathway.

Meeting ACR Dose Guidelines for CT Lung Cancer Screening in an Overweight and Obese Population.

RATIONALE AND OBJECTIVES: Lung cancer screening adoption coincides with a growing obesity epidemic. Maintaining high-quality imaging at low radiation dose is challenging in obesity. We investigate the feasibility of meeting American College of Radiology (ACR) dose guidelines for lung cancer screening in a predominantly overweight and obese population. MATERIALS AND METHODS: Radiation dose (Volumetric CT dose index [CTDIvol], dose-length product), and body mass index (BMI) were collected for baseline screening CTs December, 2012-December, 2017. Dose metrics were analyzed according to BMI classification (normal <25, overweight 25-29, obese ≥30 kg/m2), using k = 0.014 mSv/mGy*cm. Results were compared to ACR dose guidelines and mean national 2017 Lung Cancer Screening Registry dose metrics. Analysis used Kruskal-Wallis (SPSS, version 24.0.0, IBM corp, Armonk, NY). RESULTS: Study population comprised 1478 patients (49.2% [727] women: mean BMI 28.1 ± 6.5 kg/m2, 26.9% [397] normal weight, 35.9% [530] overweight, 37.2% [551] obese). ACR dose requirements were met for both genders in all BMI classifications. Dose metrics were higher in men than in women; median effective dose and CTDIvol were 1.39 (0.8-1.58) mSv and 2.78 (1.41-2.80) mGy in men versus 1.16 (0.71-1.43) mSv and 2.70 (1.4-2.78) mGy in women. There were significant differences in dose metrics between men and women in the same BMI classification and between BMI classifications (p < 0.001). Mean dose metrics in our program were considerably lower than 2017 national average- mean CTDIvol and effective dose 2.45 ± 1.14 mGy and 1.26 ± 0.59 mSv versus 3.24 mGy and 1.35 mSv, respectively for our program and nationally. Mean dose metrics were also lower in our obese patients versus obese patients nationally. CONCLUSION: ACR dose metrics for lung cancer screening were met and can be appropriately tailored in a predominantly overweight and obese population clinical program.

Bicalutamide Exhibits Potential to Damage Kidney via Destroying Complex I and Affecting Mitochondrial Dynamics.

Bicalutamide (Bic) is an androgen deprivation therapy (ADT) for treating prostate cancer, while ADT is potentially associated with acute kidney injury. Previously, we recognized Bic induced renal mitochondria dysfunction in vitro and in vivo via the ROS -HIF1α pathway. Whether OXPHOS complex, as well as mitochondrial dynamics, can be influenced by Bic via modulation of peroxisome proliferator-activated receptor coactivator 1α (PGC1α), NADPH oxidase 4 (Nox4), mitofusins 1/2 (MFN 1/2), optic atrophy 1 (OPA1), and sirtuins (SIRTs) has not been documented. Renal mesangial cell line was treated with Bic (30~60 µM) for the indicated time. SIRTs, complex I, mitochondrial dynamics- and oxidative stress-related proteins were analyzed. Bic dose-dependently reduced mitochondrial potential, but dose- and time-dependently suppressed translocase of the outer mitochondrial membrane member 20 (Tomm 20), complex I activity. Nox4 and glutathione lead to decreased NAD+/NADH ratio, with upregulated superoxide dismutase 2. SIRT1 was initially stimulated and then suppressed, while SIRT3 was time- and dose-dependently downregulated. PGC1α, MFN2, and OPA1 were all upregulated, with MFN1 and pro-fission dynamin-related protein I downregulated. Bic exhibits potential to damage mitochondria via destroying complex I, complex I activity, and mitochondrial dynamics. Long-term treatment with Bic should be carefully followed up.

Cancer PRSweb: An Online Repository with Polygenic Risk Scores for Major Cancer Traits and Their Evaluation in Two Independent Biobanks.

To facilitate scientific collaboration on polygenic risk scores (PRSs) research, we created an extensive PRS online repository for 35 common cancer traits integrating freely available genome-wide association studies (GWASs) summary statistics from three sources: published GWASs, the NHGRI-EBI GWAS Catalog, and UK Biobank-based GWASs. Our framework condenses these summary statistics into PRSs using various approaches such as linkage disequilibrium pruning/p value thresholding (fixed or data-adaptively optimized thresholds) and penalized, genome-wide effect size weighting. We evaluated the PRSs in two biobanks: the Michigan Genomics Initiative (MGI), a longitudinal biorepository effort at Michigan Medicine, and the population-based UK Biobank (UKB). For each PRS construct, we provide measures on predictive performance and discrimination. Besides PRS evaluation, the Cancer-PRSweb platform features construct downloads and phenome-wide PRS association study results (PRS-PheWAS) for predictive PRSs. We expect this integrated platform to accelerate PRS-related cancer research.

Transjugular versus Transfemoral Transcaval Liver Biopsy: A Single-Center Experience in 500 Cases.

PURPOSE: To compare the safety and efficacy of transfemoral transcaval liver biopsies (TFTC) with that of transjugular liver biopsies (TJLB) at a single tertiary-care institution. MATERIALS AND METHODS: A retrospective review was performed of 500 consecutive transvenous liver biopsies between December 2010 and December 2018. The cases included 286 TFTC patients at a median age of 54 years old (interquartile range [IQR], 42-63 years of age), 37.4% were female; and 214 TJLB patients at a median age of 55 years old (IQR, 46-61 years of age), 45.4% female. Patient demographic and laboratory data and technical and histopathological success, fluoroscopy times, and complications were recorded. Comparative statistical analyses were performed using a 2-sample test or a Wilcoxon ranked sum test for continuous variables and a chi-square test or Fisher exact test for categorical variables when appropriate. RESULTS: TFTC and TJLB data are presented as: technical success rates of 99.3% (283 of 286) and 100% (214 of 214), respectively; histopathologic success rates of 96.5% (275 of 285) and 95.8% (205 of 214), respectively; and major complication rates of 1.4% (4 of 284) and 5.6% (12 of 214), respectively (P = .009). There were no hepatic injuries in the TFTC group, whereas the TJLB group included 6 significant hepatic injuries requiring intervention. Median fluoroscopic times were 5.5 minutes (IQR, 3.9-8.6 minutes) for TFTC and 8.1 minutes (IQR, 5.2-13.1) for TJLB (P < .001). CONCLUSIONS: In this single-institution study, TFTC was associated with a lower major complication rate and lower fluoroscopy times than conventional TJLB with similar technical and histopathologic successes.

Manufacturing technology of banana-assorted breads: The fermentative characteristics affected by different banana cultivars.

Taiwan produces large quantities of bananas in the southern area. Recently, due to the export quantity has been greatly reduced, in order to efficiently maintain the banana agriculture and economy, the development of alternate uses of bananas has become urgently in need. Bananas contain a fair amount of nutrients with low glycemic index. Currently, as the bread consumption is increasing, we tried to manufacture banana-assorted breads. The desiccated powders of Musa sapientum var TC2-425 Linn [(genomically, called as Musa (AAA) (MA)] and Musa basjoo "Nam Wa" (MB) were separately incorporated at 15%, 20%, and 25% (denoted as MA15-MA25 and MB15-MB25). Results indicated that MA exhibited higher contents of moisture, ash, crude protein, and lutein, while with lower crude fat, crude fibers, carbohydrate, sodium, total soluble sugars, and pectin. The contents of taste compounds (name, samples in decreasing order) were as follows: 5'-CMP (MB25, MB20); 5'-GMP (MA25, MA20); 5'-AMP (MB25, MA15); 5'-XMP (MA25, MA20); 5'-IMP (MA25, MB20, MB25); and 5'-UMP (MA20, MA25, MB20). Hedonic scoring (HS) indicated MA15, MA20, MB15, and MB20 were more acceptable. Textural profile analysis (TPA; for 0-6 days, only 0-4 days are shown) revealed that "flavor," "mouthfeel," "hardness," "gumminess," and "chewiness" were the determinant key roles. Conclusively, due to different chemical constituent of banana, different recipes must be considered. The bread acceptability is affected by the fermentative profile which in turn is governed by the contents of soluble sugars, pectin, taste compounds, and the overall activity of yeast cells.

Bicalutamide Elicits Renal Damage by Causing Mitochondrial Dysfunction via ROS Damage and Upregulation of HIF-1.

Combined androgen blockade using bicalutamide (Bic) is a therapeutic choice for treating prostate cancer (PCa). However, even at regular clinical dosages, Bic frequently shows adverse effects associated with cardiovascular and renal damage. Previously, we found that Bic selectively damaged mesangial cells compared to tubular cells and in an in vivo rat model, we also found renal damage caused by Bic. In the present study, a rat mesangial cell model was used to further the investigation. Results indicated that Bic enhanced lactate dehydrogenase release, reactive oxygen species (ROS) production, lysosome population and kidney injury molecule-1 and decreased N-cadherin. Bic elicited mitochondrial swelling and reduced the mitochondrial potential, resulting in severe suppression of the oxygen consumption rate (OCR), maximum respiration and ATP production. The hypoxia-inducible factor (HIF)-1 transcriptional activity and messenger RNA were significantly upregulated in dose-dependent manners. The HIF-1 protein reached a peak value at 24 h then rapidly decayed. BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 and cleaved caspase-3 were dose-dependently upregulated by Bic (60 M) and that eventually led to cell apoptosis. It is suggested that Bic induces renal damage via ROS and modulates HIF-1 pathway and clinically, some protective agents like antioxidants are recommended for co-treatment.

Nifedipine Upregulates ATF6-α, Caspases -12, -3, and -7 Implicating Lipotoxicity-Associated Renal ER Stress.

Nifedipine (NF) is reported to have many beneficial effects in antihypertensive therapy. Recently, we found that NF induced lipid accumulation in renal tubular cells. Palmitic acid-induced renal lipotoxicity was found to be partially mediated by endoplasmic reticular (ER) stress, while it can also be elicited by NF in kidney cells; we examined the induction of suspected pathways in both in vitro and in vivo models. NRK52E cells cultured in high-glucose medium were treated with NF (30 µM) for 24-48 h. ER stress-induced lipotoxicity was explored by staining with thioflavin T and Nile red, transmission electron microscopy, terminal uridine nick-end labeling, and Western blotting. ER stress was also investigated in rats with induced chronic kidney disease (CKD) fed NF for four weeks. NF induced the production of unfolded protein aggregates, resulting in ER stress, as evidenced by the upregulation of glucose-regulated protein, 78 kDa (GRP78), activating transcription factor 6α (ATF6α), C/EBP-homologous protein (CHOP), and caspases-12, -3, and -7. In vitro early apoptosis was more predominant than late apoptosis. Most importantly, ATF6α was confirmed to play a unique role in NF-induced ER stress in both models. CKD patients with hypertension should not undergo NF therapy. In cases where it is required, alleviation of ER stress should be considered to avoid further damaging the kidneys.

Integrated anti-hyperlipidemic bioactivity of whole Citrus grandis [L.] osbeck fruits-multi-action mechanism evidenced using animal and cell models.

Changes in human life style have increased the incidence of obesity which has become a risk factor to human health. In Taiwan, the annual production of Citrus grandis [L.] reaches 75 000 tons, while the amount of waste fruits could reach 5%. We propose that abundant phytochemicals present in the wastes can be beneficial to attenuate obesity with hyperlipidemia. An animal Wistar rat model showed that pomelo flesh, peels, carpel (the segmental membrane), as well as the essential oil attenuated obesity as well as hyperlipidemia, and the AMPK-SREBP-PPARS pathway was involved. To further verify the mechanism, a HepG2 cell model was used to test some representative pomelo phytonutrients including limonene (Ln), γ-terpinene (γT), p-synephrine (SP), ß-sitosterol (ßS), and hesperidin (Hn). Data interestingly revealed it to be a multiple mechanism of anti-lipogenic bioactivity via downregulating the enzymes involved in both the cholesterol and triacylglyceride de novo biosynthesis (in the order of decreasing bioactivity): acetyl CoA carboxylase (Hn, SP, ßS, Ln = γT), fatty acid synthase (Ln, γT, SP, ßS, Hn), HMG-CoA synthase (Ln, Hn, SP, ßS, γT), and HMG-CoA reductase (Hn, Ln, ßS, γT, SP), and via upregulation of cholesterol-7α-monooxygenase (CYP7A1) (Hn, ßS). In addition, all pomelo fruit parts enhanced the fecal crude lipid and sterol excretion capability. Thus, fruits of C. grandis can serve as a rather promising integrative antihyperlipidemic agent.

Antrodan Alleviates High-Fat and High-Fructose Diet-Induced Fatty Liver Disease in C57BL/6 Mice Model via AMPK/Sirt1/SREBP-1c/PPARγ Pathway.

Non-alcoholic fatty liver disease (NAFLD) and -steatohepatitis (NASH) imply a state of excessive fat built-up in livers with/or without inflammation and have led to serious medical concerns in recent years. Antrodan (Ant), a purified ß-glucan from A. cinnamomea has been shown to exhibit tremendous bioactivity, including hepatoprotective, antihyperlipidemic, antiliver cancer, and anti-inflammatory effects. Considering the already well-known alleviating bioactivity of A. cinnamomea for the alcoholic steatohepatitis (ASH), we propose that Ant can be beneficial to NAFLD, and that the AMPK/Sirt1/PPARγ/SREBP-1c pathways may be involved in such alleviations. To uncover this, we carried out this study with 60 male C57BL/6 mice fed high-fat high-fructose diet (HFD) for 60 days, in order to induce NAFLD/NASH. Mice were then grouped and treated (by oral administration) as: G1: control; G2: HFD (HFD control); G3: Ant, 40 mgkg (Ant control); G4: HFD+Orlistat (10 mg/kg) (as Orlistat control); G5: HFD+Ant L (20 mg/kg); and G6: HFD+Ant H (40 mg/kg) for 45 days. The results indicated Ant at 40 mg/kg effectively suppressed the plasma levels of malondialdehyde, total cholesterol, triglycerides, GOT, GPT, uric acid, glucose, and insulin; upregulated leptin, adiponectin, pAMPK, Sirt1, and down-regulated PPARγ and SREBP-1c. Conclusively, Ant effectively alleviates NAFLD via AMPK/Sirt1/CREBP-1c/PPARγ pathway.

Astaxanthin Protects PC12 Cells against Homocysteine- and Glutamate-Induced Neurotoxicity.

Memory impairment has been shown to be associated with glutamate (Glu) excitotoxicity, homocysteine (Hcy) accumulation, and oxidative stress. We hypothesize that Glu and Hcy could damage neuronal cells, while astaxanthin (ATX) could be beneficial to alleviate the adverse effects. Using PC12 cell model, we showed that Glu and Hcy provoked a huge amount of reactive oxygen species (ROS) production, causing mitochondrial damage at EC50 20 and 10 mm, respectively. The mechanisms of action include: (1) increasing calcium influx; (2) producing ROS; (3) initiating lipid peroxidation; (4) causing imbalance of the Bcl-2/Bax homeostasis; and (5) activating cascade of caspases involving caspases 12 and 3. Conclusively, the damages caused by Glu and Hcy to PC12 cells can be alleviated by the potent antioxidant ATX.

Performance of the Vancouver Risk Calculator Compared with Lung-RADS in an Urban, Diverse Clinical Lung Cancer Screening Cohort.

Purpose: To compare the performance of the Vancouver risk calculator (VRC) with the American College of Radiology's Lung CT Screening Reporting and Data System (Lung-RADS) for a lung cancer screening cohort in an urban, diverse clinical setting. Materials and Methods: This study included a total of 486 patients with lung nodules (63 years ± 5.2 [standard deviation], 261 female patients), 448 of whom had lung nodules that were subsequently classified as benign and 38 of whom had those that were classified as malignant. The mean follow-up time was 40.0 months ± 14. Institutional review board approval was obtained for this Health Insurance Portability and Accountability Act-compliant retrospective study, and a waiver of informed consent was received. All patients undergoing lung cancer screening who underwent an initial baseline screening CT between December 2012 and June 2016 that demonstrated a nodule and had at least 1 year of follow-up comprised the study population. Each examination was assigned a Lung-RADS score between 2 and 4B, with 4A and 4B considered as showing positive results. The VRC calculates the risk of cancer at different thresholds using nine variables related to patient and imaging characteristics. Analysis was performed per patient based on the largest nodule. Lung-RADS and VRC using the 5% threshold were compared to assess diagnostic performance in determining the risk of developing lung cancer in a patient with a nodule found at screening CT. The McNemar test was used to compare differences in performance between Lung-RADS and VRC. Results: Lung-RADS resulted in nine false-positive and 16 false-negative findings, whereas VRC with a 5% threshold resulted in 29 false-positive and 10 false-negative findings. Overall sensitivity and specificity for Lung-RADS was 58.0% and 98.0%, and for VRC with a 5% threshold was 73.7% and 93.5%, respectively (P = .313, P < .001, respectively). Conclusion: The VRC performs well in an urban, diverse lung cancer screening program. Further studies may be directed at determining whether its use in conjunction with Lung-RADS leads to improved lung cancer detection.Keywords: CT, Lung, Thorax© RSNA, 2020.