Ginseng Glucosyl Oleanolate from Ginsenoside Ro, Exhibited Anti-Liver Cancer Activities via MAPKs and Gut Microbiota In Vitro/Vivo.

Ginseng is widely recognized for its diverse health benefits and serves as a functional food ingredient with global popularity. Ginsenosides with a broad range of pharmacological effects are the most crucial active ingredients in ginseng. This study aimed to derive ginseng glucosyl oleanolate (GGO) from ginsenoside Ro through enzymatic conversion and evaluate its impact on liver cancer in vitro and in vivo. GGO exhibited concentration-dependent HepG2 cell death and markedly inhibited cell proliferation via the MAPK signaling pathway. It also attenuated tumor growth in immunocompromised mice undergoing heterograft transplantation. Furthermore, GGO intervention caused a modulation of gut microbiota composition by specific bacterial populations, including Lactobacillus, Bacteroides, Clostridium, Enterococcus, etc., and ameliorated SCFA metabolism and colonic inflammation. These findings offer promising evidence for the potential use of GGO as a natural functional food ingredient in the prevention and treatment of cancer.

High-Performance Lithium Metal Batteries Enabled by a Fluorinated Cyclic Ether with a Low Reduction Potential.

Electrolyte engineering is crucial for developing high-performance lithium metal batteries (LMB). Here, we synthesized two cosolvents methyl bis(fluorosulfonyl)imide (MFSI) and 3,3,4,4-tetrafluorotetrahydrofuran (TFF) with significantly different reduction potentials and add them into LiFSI-DME electrolytes. The LiFSI/TFF-DME electrolyte gave an average Li Coulombic efficiency (CE) of 99.41 % over 200 cycles, while the average Li CEs for MFSI-based electrolyte is only 98.62 %. Additionally, the TFF-based electrolytes exhibited a more reversible performance than the state-of-the-art fluorinated 1,4-dimethoxylbutane electrolyte in both Li||Cu half-cell and anode-free Cu||LiNi0.8 Mn0.1 Co0.1 O2 full cell. More importantly, the decomposition product from bis(fluorosulfonyl)imide anion could react with ether solvent, which destroyed the SEI, thus decreasing cell performance. These key discoveries provide new insights into the rational design of electrolyte solvents and cosolvents for LMB.

Metabolite analysis of soybean oil on promoting astaxanthin production of Phaffia rhodozyma.

BACKGROUND: Astaxanthin is a carotenoid with strong antioxidant property. In addition, it has anti-cancer, anti-tumor, anti-inflammatory and many other functions. The micro-organisms that mainly produce astaxanthin are Haematococcus pluvialis and Phaffia rhodozyma. Compared with H. pluvialis, P. rhodozyma has shorter fermentation cycle and easier to control culture conditions, but the yield of astaxanthin in P. rhodozyma is low. This article studied how to improve the astaxanthin production of P. rhodozyma. RESULTS: The results showed that when 10 mL L-1 soybean oil was added to the culture medium, astaxanthin production increased significantly, reaching 7.35 mg L-1 , which was 1.4 times that of the control group, and lycopene and ß-carotene contents also increased significantly. Through targeted metabolite analysis, the fatty acids in P. rhodozyma significantly increased under the soybean oil stimulation, especially the fatty acids closely related to the formation of astaxanthin esters, included palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1n9), linoleic acid (C18:2n6), α-linolenic acid (C18:3n3) and γ-linolenic acid (C18:3n6), thereby increasing the astaxanthin esters content. CONCLUSION: It showed that the addition of soybean oil can promote the accumulation of astaxanthin by promoting the increase of astaxanthin ester content. © 2022 Society of Chemical Industry.

Ameliorative effect of Lactobacillus plantarum Lp2 against cyclophosphamide-induced liver injury in mice.

Cyclophosphamide (CTX) is a widely used anticancer drug that can cause liver injury, but there is no effective treatment available at present. The antioxidant properties of Lactobacillus plantarum Lp2 in vitro and its effect on CTX-induced liver injury in mice were investigated thoroughly. The order of antioxidant capacity of the fermentate of Lp2 was as followed: fermented supernatant > cell-free extract > intact cell. BALB/c mice were intraperitoneally injected with 80 mg/kg BW/d CTX for 3 days to build a liver injury model, then treated with Lp2 fermented supernatant (Lp2-s) and Lp2 culture broth (Lp2). After 10 days, the indicators of oxidative stress and liver injury were measured. Both Lp2-s and Lp2 restored the levels of T-SOD, CAT, GSH-Px, MDA, GSH, ALT, and AST. The western blotting results showed that Lp2-s and Lp2 ameliorated CTX-induced oxidative damage and hepatocyte apoptosis via inhibiting MAPKs pathway and strengthening Nrf2/HO-1/NQO1 antioxidant defense system, thus inhibiting the mitochondrial-mediated apoptosis pathway. Therefore, both Lp2-s and Lp2 had similar protective effects on CTX-induced liver injury.

The effect of Lactobacillus rhamnosus B10 on alcoholic liver injury and intestinal microbiota in alcohol-induced mice model.

Lactobacillus rhamnosus B10 (L. rhamnosus B10) isolated from the baby feces was given to an alcohol mice model, aiming to investigate the effects of L. rhamnosus B10 on alcoholic liver injury by regulating intestinal microbiota. C57BL/6N mice were fed with liquid diet Lieber-DeCarli with or without 5% (v/v) ethanol for 8 weeks, and treated with L. rhamnosus B10 at the last 2 weeks. The results showed that L. rhamnosus B10 decreased the serum total cholesterol (1.48 mmol/L), triglycerides (0.97 mmol/L), alanine aminotransferase (26.4 U/L), aspartate aminotransferase (14.2 U/L), lipopolysaccharide (0.23 EU/mL), and tumor necrosis factor-α (138 pg/mL). In addition, L. rhamnosus B10 also reduced the liver triglycerides (1.02 mmol/g prot), alanine aminotransferase (17.8 mmol/g prot) and aspartate aminotransferase (12.5 mmol/g prot) in alcohol mice, thereby ameliorating alcohol-induced liver injury. The changes of intestinal microbiota composition on class, family and genus level in cecum were analyzed. The intestinal symbiotic abundance of Firmicutes was elevated while gram-negative bacteria Proteobacteria and Deferribacteres was decreased in alcohol mice treated with L. rhamnosus B10 for 2 weeks. In summary, this study provided evidence for the therapeutic effects of probiotics on alcoholic liver injury by regulating intestinal flora.

Salidroside alleviates liver inflammation in furan-induced mice by regulating oxidative stress and endoplasmic reticulum stress.

Furan is a genotoxic and carcinogenic toxicant formed during the food thermal processing. Our previous studies confirmed that salidroside (SAL) displayed excellent protective effects against furan-induced hepatotoxicity and inflammation, whereas the underlying mechanism was still unclear. In the current study, Balb/c mice were divided to the control group (CON), the furan model group (FUR8, 8 mg/kg BW furan for 30 days) and SAL intervention groups (SAL10/20/40, 8 mg/kg BW furan for 30 days + 10/20/40 mg/kg BW SAL from day 16 to day 30). The alleviative effects and the mechanisms of SAL against furan-induced liver inflammation in mice were investigated through oxidative stress (OS) and endoplasmic reticulum stress (ERS). Liver metabonomics data, molecular docking and Western-blotting results implied that SAL suppressed the activity and the high expression of hepatic CYP2E1, and alleviated liver OS induced by furan. Levels of key markers (GRP78, CHOP and Caspase-12) of ERS and proteins in IRE1α pathway of the UPR branch increased by furan were prominently reduced after SAL treatment. Levels of phosphorylated proteins JNK, ERK, p38, IKKα/ß, IκB and p65 in MAPK and NF-κB pathways were also suppressed by SAL. We further confirmed that SAL inhibited furan-induced inflammation by reducing the levels of NLRP3, ASC, Cleaved Caspase-1 and IL-1ß and decreasing the production of pro-inflammatory cytokines. Our results shed light into the alleviating mechanisms behind furan-induced liver inflammation, and suggested that SAL inhibited OS, ERS and related MAPK and NF-κB pathways and therefore inhibited the NLRP3 inflammasome activation, which may be its potential mechanism of alleviating liver inflammation.

MiR-193b-5p protects BRL-3A cells from acrylamide-induced cell cycle arrest by targeting FoxO3.

Acrylamide (AA), an important by-product of the Maillard reaction, has been reported to be genotoxic and carcinogenic. The present study employed miRNAs to investigate the toxic mechanism of AA and their role against AA toxicity. Deep sequencing of small RNA libraries was performed and miR-193b-5p was applied for further study. AA significantly reduced the level of miR-193b-5p and its ectopic expression promoted cell cycle G1/S transition and cell proliferation by upregulating the cyclin-dependent kinase regulator Cyclin D1 and downregulating the cyclin-dependent kinase inhibitor p21, while miR-193b-5p inhibitor led to the opposite results. Dual luciferase assay demonstrated miR-193b-5p regulated the expression of FoxO3 by directly targeting the FoxO3 3'-untranslated region (3'-UTR). Knockdown of FoxO3 induced cell cycle G1/S transition and cell proliferation, which was suppressed by the inhibition of miR-193b-5p but promoted by miR-193b-5p mimics. MiR-193b-5p inhibitor strengthened the effect of FoxO3, contrary to the effect of miR-193b-5p mimics. In conclusion, miR-193b-5p acted as a regulator of cell cycle G1/S transition and cell proliferation by targeting FoxO3 to mediate the expression of p21 and Cyclin D1.

[Modified (Wu's) esophagectomy for a huge thoracic esophageal squamous cell carcinoma 18.3 cm in length].

An esophageal squamous cell carcinoma measuring 18.3 cm in length and 5 cm in diameter was found in the mediastinum of a 53-year man. The patient underwent a modified 3-stage esophagectomy and an esophagogastrostomy at the cervical level (Wu's method). The operation was performed smoothly and the patient recovered uneventfully after the operation. The patient was followed up for 6 months after discharge and reported no difficulties in eating with improved quality of life. This case represents the world's longest esophageal cancer that had been surgically removed. Local advanced esophageal cancer should be removed immediately to prevent potential occurrence of esophageal obstruction, tracheoesophageal fistula or aorto-esophageal fistula.

High DEPTOR expression correlates with poor prognosis in patients with esophageal squamous cell carcinoma.

OBJECTIVE: The disheveled, Egl-10, and pleckstrin (DEP) domain containing mammalian target of rapamycin (mTOR)-interacting protein (DEPTOR) is a binding protein containing mTOR complex 1 (mTORC1), mTOR complex 2 (mTORC2), and an endogenous mTOR inhibitor. DEPTOR shows abnormal expressions in numerous types of solid tumors. However, how DEP-TOR is expressed in esophageal squamous cell carcinoma (ESCC) remains elusive. METHODS: The expression of DEPTOR in 220 cases of ESCC and non-cancerous adjacent tissues was detected by immunohistochemistry. DEPTOR levels in ESCC and paired normal tissue were quantified using reverse transcription-polymerase chain reaction and Western blot analysis to verify the immunohistochemical results. The relationship between DEPTOR expression and the clinicopathological features of ESCC was analyzed based on the results of immunohistochemistry. Finally, we analyzed the relationship between DEPTOR expression and the prognosis of patients with ESCC. RESULTS: Immunohistochemical staining showed that the expression rate of DEPTOR in ESCC tissues was significantly increased. DEPTOR mRNA and protein expression was significantly higher in ESCC tissues than in normal adjacent esophageal squamous tissues. High DEPTOR expression was significantly correlated with regional lymph node status in the TNM stage of patients with ESCC. Kaplan-Meier survival curves showed that the rate of overall survival was significantly lower in patients with high DEPTOR expression than in those with low DEPTOR expression. Additionally, high DEPTOR expression was an independent prognostic predictor for ESCC patients. CONCLUSION: High DEPTOR expression is an independent prognostic biomarker indicating a worse prognosis for patients with ESCC.

Methylenetetrahydrofolate reductase 677TT genotype may be associated with an increased lung cancer risk in North China: an updated meta-analysis.

BACKGROUND: Although many epidemiology studies have investigated the methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and their associations with lung cancer (LC), definite conclusions cannot be drawn. To clarify the effects of MTHFR polymorphisms on the risk of LC, we performed a meta-analysis in Chinese populations. MATERIAL/METHODS: Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) until 16 February 2014. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. RESULTS: A total of 11 studies with 2487 LC cases and 3228 controls were included in this meta-analysis. Overall, no significant association was found between MTHFR C677T polymorphism and LC risk when all studies in Chinese populations were pooled into this meta-analysis. In subgroup analyses stratified by geographical location and source of controls, significantly increased risk was found in North China (T vs. C: OR=1.28, 95% CI: 1.14-1.44; TT vs. CC: OR=1.67, 95% CI: 1.33-2.10; TT + CT vs. CC, OR=1.39, 95% CI=1.15-1.69; TT vs. CC + CT: OR=1.46, 95% CI: 1.03-2.06) and in population-based studies (TT vs. CC: OR=1.37, 95% CI: 1.14-1.65; TT vs. CC + CT: OR=1.25, 95% CI: 1.07-1.45). CONCLUSIONS: This meta-analysis provides evidence that MTHFR C677T polymorphism may contribute to LC development in North China. Studies with larger sample sizes and wider spectrum of populations are warranted to verify this finding.