Arterial chemotherapy for hepatocellular carcinoma in China: consensus recommendations.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.

Insight into the phenolics and antioxidant activity of Indian jujube (Ziziphus mauritiana Lamk) peel and pulp subjected to the simulated digestion.

To evaluate the release and activity of Indian jujube phenolics in vivo, its peel and pulp were subjected to simulated digestions. The phenolics content and antioxidant activity of the digested samples were determined. The results showed that the total phenolics/flavonoids in the peel were respectively 4.63 and 4.48 times higher than that in the pulp. The release of phenolics and flavonoids respectively increased by 79.75% and 39.98% in the peel and 86.34% and 23.54% in the pulp after the intestinal digestion. The correlation between the total phenolics/flavonoids and antioxidant activity was higher in the peel (r > 0.858, p < 0.01) than that in the pulp. The phenolics profiles of the peel were almost the same after the digestion, and four phenolics including naringenin tri-glycoside, quercetin-3-O-[(2-hexosyl)-6-rhamnosyl] -hexoside, quercetin-3-O-pentosylhexoside and quercetin-3-O-(2-pentosyl -rhamnoside)-4'-O-rhamnoside were found to be the main flavonoids of Indian jujube peel, and they showed high recovery (>89.88%) during the digestion, implying that these phenolics may play a vital role in the function of Indian jujubes.

Profile and activity of phenolic antioxidants in chrysanthemum (Huangshan Gongju) as affected by simulated digestions.

The phenolics are the main bioactive substances of Huangshan Gongju, a famous chrysanthemum of China, but their digestive characteristics are still unknown. To explore the digestive properties of Huangshan Gongju phenolics, the flower was extracted and subjected to simulated digestions, and their phenolic profile and activity were analyzed. The results indicated that the total phenolics content and antioxidant activity of the extract varied with the simulated digestion steps, and they generally decreased in the oral and small intestine digestions but increased in the gastric digestion, and high correlations were detected between the total phenolics content and antioxidant activity (0.873 < r < 0.979, p < .01). The change of phenolic profile during the simulated digestions was similar to that of total phenolics content, and six individual phenolics were identified and quantified, and three of them, including chlorogenic acid, apigenin-7-O-rutinoside, and apigenin-7-O-6″-acetylglucoside showed higher recovery (>64.29%), implying they may be the main functional phenolics of Huangshan Gongju. PRACTICAL APPLICATIONS: This study proved that most phenolics in Huangshan Gongju were relatively stable during digestion. The finding may guarantee the application of Huangshan Gongju in the field of functional foods.

Evaluation of digestibility differences for apple polyphenolics using in vitro elderly and adult digestion models.

We evaluated the in vitro digestibility of apple polyphenols mimicking elderly and adult digestion models (dynamic and static systems). The digestibility of total apple polyphenols in small intestine was much higher in the adult dynamic system (62 µg/100 g fresh apple) compared to the static system (20 µg/100 g fresh apple) and elderly dynamic digestion conditions (33 µg/100 g fresh apple). Elderly in vitro static digestion showed better antioxidant activity than the adult system (OH and ABTS+ methods). Thus, the in vitro dynamic digestion system can more truly reflect the digestion of apple polyphenols than static digestion system. Moreover, elderly digestion conditions negatively influenced the digestibility of apple polyphenols including chlorogenic acid, epicatechin, phlorizin, rutin, phloretin, hyperoside, proanthocyanidin B2, and quercetin. Hence, appropriate selection of in vitro digestion models for elderly is a prerequisite to exploring the digestibility of phytochemicals for the development of functional food products for elderly.

Characterization of functional chocolate formulated using oleogels derived from ß-sitosterol with γ-oryzanol/lecithin/stearic acid.

With an aim to prepare the functional chocolate, corn oil was used as the base oil and ß-sitosterol was combined with oryzanol/stearic acid/lecithin to prepare respective oleogels (GO, SO, and LO). Oleogels (12%) were prepared by adding compound oleogelators at different ratios [GO-2:3, SO-1:4, and LO-4:1 (w/w)] in corn oil. The microstructure, interaction, thermodynamic, crystalline, and rheological behavior of formulated oleogels were studied by microscopic observation, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and rotational rheometer, respectively. The results showed that GO had the strongest gel forming ability and the densest gel crystallization network. Moreover, chocolate prepared with GO (cocoa butter and oleogels-1:1) had the similar texture, crystal structure, rheological, and sensory properties to that of dark chocolate. This study provides the possibility for the wider application of oleogel prepared with lower saturated and trans-fatty acids in the chocolate industry.

Solvent effect on phenolics and antioxidant activity of Huangshan Gongju (Dendranthema morifolium (Ramat) Tzvel. cv. Gongju) extract.

Huangshan Gongju was extracted with organic solvents (ethanol, methanol and acetone) of different concentrations (0-90%), and the extracts' phenolic content and antioxidant activity, as well as the correlations between them were examined. With the increasing concentration of organic solvent, the total phenolic compound (TPC) increased continuously and met its maximum at 70% acetone, whereas the total flavonoid compound (TFC) and most individual phenolics met their maximums at 70% ethanol. Similar changes occurred to the antioxidant activity, including DPPH and ABTS scavenging activities, and their maximums were respectively found at 50% acetone and 70% ethanol. The antioxidant activity correlated strongly with TPC/TFC (r > 0.954, p < 0.01) and individual phenolics (r > 0.886, p < 0.05), and the strongest correlations between them were mainly given by luteolin-7-O-glucoside (r > 0.975, p < 0.001). These results suggested that high content organic solvent (50-70%) was beneficial to obtain Huangshan Gongju extracts of higher phenolic content and antioxidant activity, and 70% ethanol may be the promising solvent. Besides, phenolics were found to be the main antioxidants of Huangshan Gongju extracts, and flavonoids especially luteolin-7-O-glucoside may play more important roles in the antioxidant activity.

Comparative study of chemical compositions and antioxidant activities of Zhizi fruit extracts from different regions.

The fruits of Gardenia jasminoides Ellis are folk medicines in China and their major components are geniposide and water soluble pigment crocins. This study compared the chemical profiles and free radical scavenging activities of two Zhizi species from five provinces of China, including Jiangxi, Anhui, Hunan, Sichuan and Henan. The results showed that Jiangxi Zhizi contained higher levels of volatiles (71.84%), crocins (20.38 mg/g), geniposide (31.36 mg/g) and flavonoids (84.42 µg quercetin/mg) than four other Zhizi fruits; whereas Hunan Zhizi provided higher total phenolics (33.81 µg catechin/mg) and ABTS/DPPH radical scavenging activities. These findings implied that Jiangxi Zhizi would be suitable for extraction of gardenia yellow and geniposide, as well as preparation of essential oil. This information may provide valuable guidance for application of Zhizi fruits to biomedicine industry in China.

Shaft Function of Kinesin-1's α4 Helix in the Processive Movement.

INTRODUCTION: Kinesin-1 motor is a molecular walking machine constructed with amino acids. The understanding of how those structural elements play their mechanical roles is the key to the understanding of kinesin-1 mechanism. METHODS: Using molecular dynamics simulations, we investigate the role of a helix structure, α4 (also called switch-II helix), of kinesin-1's motor domain in its processive movement along microtubule. RESULTS: Through the analysis of the structure and the interactions between α4 and the surrounding residues in different nucleotide-binding states, we find that, mechanically, this helix functions as a shaft for kinesin-1's motor-domain rotation and, structurally, it is an amphipathic helix ensuring its shaft functioning. The hydrophobic side of α4 consists strictly of hydrophobic residues, making it behave like a lubricated surface in contact with the core ß-sheet of kinesin-1's motor domain. The opposite hydrophilic side of α4 leans firmly against microtubule with charged residues locating at both ends to facilitate its positioning onto the intra-tubulin groove. CONCLUSIONS: The special structural feature of α4 makes for an effective reduction of the conformational work in kinesin-1's force generation process.

Methyl protodioscin from Polygonatum sibiricum inhibits cervical cancer through cell cycle arrest and apoptosis induction.

Methyl protodioscin (MPD) is a steroid saponin which has been well known for its pharmacological properties. Herein, we evaluated the anti-cancer activity of MPD for proliferation inhibition and apoptosis induction in Hela cells. MPD was purified from the rhizoma of Polygonatum sibiricum primarily and identified by HPLC, UPLC-TOF-MS/MS and NMR analysis, respectively. Results showed that MPD repressed cell proliferation at IC50 of 18.49 µM, altered cell morphology, arrested the cell cycle in G2/M phase, facilitated the generation of intracellular ROS and led to cell apoptosis in a concentration-dependent manner. Furthermore, MPD treatment promoted death receptor pathway and mitochondrial pathway efficiently. The inhibition of Caspase-8 and Caspase-9 proteins in these pathways abolished the apoptosis significantly, further demonstrated the mechanism of MPD-induced apoptosis. These findings offer novel information that MPD may be considered as a possible natural anti-cancerous agent in the form of functional foods or medicinal products.

Transarterial chemoembolization versus best supportive care for patients with hepatocellular carcinoma with portal vein tumor thrombus：a multicenter study.

BACKGROUND: This study aims to compare the efficacy and safety of treatment after transarterial chemoembolization(TACE) with best supportive care (BSC) in patients with hepatocellular carcinoma (HCC) with PVTT. METHODS: This retrospective study was conducted on 1,040 patients with HCC with PVTT who were treated either with TACE (n = 675) or BSC (n = 365). BSC did not include sorafenib. The two groups of patients were compared with or without propensity score matching. A subgroup analysis was subsequently performed by stratifying patients according to the stages of PVTT in the Cheng's PVTT classification. RESULTS: In PVTTtypes I-III, TACE was associated with significantly better overall survival (OS) thanBSC (P < 0.05). Within each type of PVTT for patients who received TACE or BSC, OS was significantly worse in patients with type IVPVTT than in any of the other three types of PVTT (all P < 0.05). TACE was associated with better long-termOS than BSC after propensity score matching or on stratification by the PVTT types. CONCLUSION: TACE was associated with better OS than BSC in HCC patients with PVTT types I-III but not type IV. Patients with type IV PVTT showed the worst prognosis, regardless of whether TACE or BSC was used.

Effect of lactic acid bacteria fermentation on tannins removal in Xuan Mugua fruits.

The present study was conducted for developing a new method to reduce the tannins content of Xuan Mugua fruits. Lactic acid bacteria fermentation-like incubation was explored as an efficient method to reduce the astringency of Mugua fruits by reducing tannins content. To ensure the efficient removal of tannins, the fermentation conditions were optimized such as temperature, time, and ratio of bacteria to Mugua. Bacteria were able to reduce 78% of the tannins content in Mugua under the optimized conditions as assessed by the methylcellulose perceptible tannins assay. Meanwhile, the active components including polysaccharides, triterpenes, and antioxidants of Mugua with bacterial incubation were also explored, which showed the significant decrease compared to non-fermented Mugua. However, the trend for flavor components was different. This research provides a natural method to solve the astringency problem of these fruits and it will extend their application in food industry.

Molecular mechanism and inhibitory targets of dioscin in HepG2 cells.

Dioscin has been known for its anti-cancer activity; however, its detailed molecular mechanisms have not been studied so far. Herein, we evaluated the anti-cancer activity of dioscin for proliferation inhibition and apoptosis in HepG2 cancer cells. Initially, dioscin was purified and identified from Polygonatum sibiricum by HPLC, MS, and NMR analysis, respectively. Dioscin inhibited the cell multiplication at IC50 of 8.34 µM, altered the cell morphology, arrested the cell cycle in G2/M phase and led to considerable programmed cell death. Furthermore, it has efficiently promoted the mitochondrial pathway and death receptor pathway. The inhibition of Caspase-8 and Caspase-9 proteins in these pathways abolished the dioscin induced apoptosis significantly; while dioscin inhibited the PI3K/Akt/mTOR pathway. Moreover, dioscin exposure led to enhanced intracellular ROS generation and the mRNA expression of JNK gene which emphasized their involvement in the apoptosis process in HepG2 cells.

Antioxidant and antibacterial evaluation of polysaccharides sequentially extracted from onion (Allium cepa L.).

We investigated the antioxidant and antimicrobial potential of sequentially extracted onion polysaccharide fractions namely HBSS, CHSS, DASS and CASS. The different antioxidant assays indicated that ACLPs exhibited potentially appreciable antioxidant activity in a dose-dependent manner. Among all the fractions, CHSS rendered the highest antioxidant action towards ABTS radical cations (97.52%), Fe2+ chelating (98.94%) and superoxide anion radical scavenging (76.27%). Whereas, HBSS possessed the highest potential for DPPH radicals (93.68%), hydroxyl radicals (65.12%) as well as for reducing power (0.559). CASS exhibited the highest lipid peroxidation inhibition (86.43%), while, DASS showed the best ß-carotene bleaching inhibition (92.26%). Furthermore, regardless of the bacterial strain, DASS represented the strongest antibacterial activity on the basis of largest inhibition zone, the lowest minimal inhibitory concentration and maximum inhibition of bacterial growth in liquid medium. Overall results indicated that ACLPs hold a promise as potential natural antioxidant additives and antimicrobial agents for formulating the functional foods with potential applications in the medical and food industries.

Effects of extraction methods on the rheological properties of polysaccharides from onion (Allium cepa L.).

In this work we described the rheological properties of polysaccharides (HBSS, CHSS, DASS, CASS) sequentially extracted from onion (Allium cepa L.). Four onion polysaccharides (ACLPs) solutions resulted into significant differences on their rheological properties. ACLPs solutions showed non-Newtonian shear-thinning behavior over the range of 0.5-2.5%. At concentration of 1%, the apparent viscosity of CHSS was observed to be the highest. The apparent viscosity of ACLPs solutions decreased with the acidic pH (4.0) or alkaline pH (10.0) which was further declined at higher temperature (90 °C). After the addition of various salts, ACLPs had apparent differences on apparent viscosity. The G' (storage modulus) and G″ (loss modulus) of ACLP solutions were increased with increasing oscillation frequency. Moreover, the crossover value of oscillation frequency gradually decreased with increasing concentration of ACLPs. Our results exhibited that among the ACLPs, CHSS can be used as supplements in the food industry as thickening agent, gelling agent and stabilizer.

Insights into physicochemical and functional properties of polysaccharides sequentially extracted from onion (Allium cepa L.).

Onion polysaccharides (ACLP) were sequentially extracted with four different solvents (hot buffer, chelating agent, dilute alkaline and concentrated alkaline) and obtained four fractions, named as HBSS, CHSS, DASS and CASS, respectively. The present studies characterized the ACLP concerning its physicochemical and functional properties. Monosaccharides analysis revealed that mannose (81.68%) was the dominant sugar in HBSS and galactose (67.59%) was the most in CASS. Similarly, CHSS and DASS possessed mannose and galactose as major sugar, which were 25.80% and 31.37%, 20.33% and 33.96%, respectively. The obtained molecular weight of ACLPs were 7.702×103 (HBSS), 4.690×103 (CHSS), 4.943×103 (DASS) and 1.390×103kDa (CASS). CASS resulted in the strongest solubility, fat-binding capacity, foam capacity and foam stability whereas, HBSS showed the highest thermal stability. DASS showed the best hygroscopicity and the best moisture retention was obtained by CHSS. Subsequently, the emulsifying activity and emulsifying stability were the highest for HBSS and the longest for of CASS, respectively. The rheological properties of CHSS exhibited the largest viscosity. Our results indicated that all factions could be considered as functional polysaccharides according to their respective characteristics, which have vast potential in food production.

Transarterial chemoembolization compared with conservative treatment for advanced hepatocellular carcinoma with portal vein tumor thrombus: using a new classification.

We aimed to compare the survival benefit of transarterial chemoembolization (TACE) with conservative treatment for patients with advanced hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT), furthermore, to reveal which PVTT types benefit from TACE treatment. From August 2007 to January 2010, a prospective controlled study was performed on consecutive patients with advanced HCC and PVTT. Of a total of 150 patients, 115 were treated with TACE (lipiodol and anticancer agents ± gelatin sponge embolization), and 35 who refused to accept the procedure were treated with conservative treatment. We performed survival analysis of the two treatment groups and then stratified by a new classification of PVTT that was divided into four types. Overall survival was significantly better in the TACE group than in the conservative group (8.67 months vs. 1.4 months, P<0.001). The overall median survival for types I-IV PVTT were 12.0, 8.3, 5.0, and 2.43 months (P<0.01). On subgroup analysis of PVTT, the median survival in the TACE group compared with conservative group for type I, II, III, and IV PVTT was 19.0 months versus 4.0 months, 11.0 months versus 1.43 months, 7.1 months versus 1.3 months, and 4.0 months versus 1.0 months, respectively (P<0.01). The TACE group had significantly better survival than the conservative group for different extent of PVTT. TACE is an effective treatment mode compared with conservative treatment for HCC and PVTT and may provide a significantly better survival benefit for different extent of PVTT.

Absence of cellular stress in brain after hypoxia induced by arousal from hibernation in Arctic ground squirrels.

Although hypoxia tolerance in heterothermic mammals is well established, it is unclear whether the adaptive significance stems from hypoxia or other cellular challenge associated with euthermy, hibernation, or arousal. In the present study, blood gases, hemoglobin O2 saturation (S(O2), and indexes of cellular and physiological stress were measured during hibernation and euthermy and after arousal thermogenesis. Results show that arterial O2 tension (Pa(O2)) and S(O2) are severely diminished during arousal and that hypoxia-inducible factor (HIF)-1alpha accumulates in brain. Despite evidence of hypoxia, neither cellular nor oxidative stress, as indicated by inducible nitric oxide synthase (iNOS) levels and oxidative modification of biomolecules, was observed during late arousal from hibernation. Compared with rats, hibernating Arctic ground squirrels (Spermophilus parryii) are well oxygenated with no evidence of cellular stress, inflammatory response, neuronal pathology, or oxidative modification following the period of high metabolic demand necessary for arousal. In contrast, euthermic Arctic ground squirrels experience mild, chronic hypoxia with low S(O2) and accumulation of HIF-1alpha and iNOS and demonstrate the greatest degree of cellular stress in brain. These results suggest that Arctic ground squirrels experience and tolerate endogenous hypoxia during euthermy and arousal.

Ascorbate distribution during hibernation is independent of ascorbate redox state.

Distribution of ascorbate into tissues is an essential process in ascorbate antioxidant defense. Hibernating animals are studied as a model of tolerance to ischemia-reperfusion because of their tolerance to fluctuations in blood flow associated with prolonged torpor and periodic arousal episodes. Throughout hibernation, plasma ascorbate concentration ([Asc](p)) repetitively increases during torpor, then falls during periodic arousal bouts. We previously proposed that high [Asc](p) provides a ready source of antioxidant protection for distribution to the central nervous system and peripheral tissues during arousal. Here we tested whether deliberate oxidation of plasma ascorbate by intravenous administration of ascorbate oxidase (AO), prior to arousal, compromised tissue levels of ascorbate or the other water-soluble antioxidants, glutathione (GSH) and urate. Although AO decreased [Asc](p) to below the level of detection during torpor and after arousal, ascorbate oxidation did not decrease post-arousal tissue levels of reduced ascorbate, glutathione, or urate in any tissue examined, except liver. The data imply that ascorbate is taken up equally well into brain and other tissues as either ascorbate or its oxidized product dehydroascorbate, with subsequent intracellular reduction of dehydroascorbate. Lack of effect of ascorbate oxidation on tissue levels of GSH or urate indicates that dehydroascorbate uptake and reduction do not compromise tissue concentrations of these other water-soluble antioxidants. Thus, we show equal availability of reduced and oxidized plasma ascorbate during metabolically demanding thermogenesis and reperfusion associated with arousal from hibernation.