The effect of metabolism-related lifestyle and clinical risk factors on digestive system cancers in East Asian populations: a two-sample Mendelian randomization analysis.

Metabolic factors play a critical role in the development of digestive system cancers (DSCs), and East Asia has the highest incidence of malignant tumors in the digestive system. We performed a two-sample Mendelian randomization analysis to explore the associations between 19 metabolism-related lifestyle and clinical risk factors and DSCs, including esophageal, gastric, colorectal, hepatocellular, biliary tract, and pancreatic cancer. The causal association was explored for all combinations of each risk factor and each DSC. We gathered information on the instrumental variables (IVs) from various sources and retrieved outcome information from Biobank Japan (BBJ). The data were all from studies of east Asian populations. Finally, 17,572 DSCs cases and 195,745 controls were included. Our analysis found that genetically predicted alcohol drinking was a strong indicator of gastric cancer (odds ratio (OR) = 0.95; 95% confidence interval (CI): 0.93-0.98) and hepatocellular carcinoma (OR = 1.11; 95% CI: 1.05-1.18), whereas coffee consumption had a potential protective effect on hepatocellular carcinoma (OR = 0.69; 95% CI: 0.53-0.90). Triglyceride was potentially associated with a decreased risk of biliary tract cancer (OR = 0.53; 95% CI: 0.34-0.81), and uric acid was associated with pancreatic cancer risk (OR = 0.59; 95% CI: 0.37-0.96). Metabolic syndrome (MetS) was associated with esophageal and gastric cancer. Additionally, there was no evidence for a causal association between other risk factors, including body mass index, waist circumference, waist-to-hip ratio, educational levels, lipoprotein cholesterol, total cholesterol, glycine, creatinine, gout, and Graves' disease, and DSCs. The leave-one-out analysis revealed that the single nucleotide polymorphism (SNP) rs671 from the ALDH2 gene has a disproportionately high contribution to the causal association between alcohol drinking and gastric cancer and hepatocellular carcinoma, as well as the association between coffee consumption and hepatocellular carcinoma. The present study revealed multiple metabolism-related lifestyle and clinical risk factors and a valuable SNP rs671 for DSCs, highlighting the significance of metabolic factors in both the prevention and treatment of DSCs.

Colonic microflora and plasma metabolite-based comparative analysis of unilateral ureteral obstruction-induced chronic kidney disease after treatment with the Chinese medicine FuZhengHuaYuJiangZhuTongLuo and AST-120.

Background: Many researchers have investigated the use of Chinese herbs to delay the progression of chronic kidney disease (CKD) through their effects on colonic microflora and microbiota-derived metabolites. However, whether FuZhengHuaYuJiangZhuTongLuo (FZHY) has effects that are similar to those of AST-120 on CKD needs to be elucidated. Methods: In this study, we compared the effects of FZHY and AST-120 on the colonic microbiota and plasma metabolites in the CKD rat model. We developed a unilateral ureteral obstruction (UUO)-induced CKD rat model and then administered FZHY and AST-120 to these model rats. Non-targeted metabolomic LC-MS analysis, 16S rRNA sequencing, and histopathological staining were performed on plasma, stool, and kidney tissues, respectively, and the joint correlation between biomarkers and metabolites of candidate bacteria was analyzed. Results: Our results showed that administering FZHY and AST-120 effectively ameliorated UUO-induced abnormal renal function and renal fibrosis and regulated the composition of microbiota and metabolites. Compared to the UUO model group, the p_Firmicutes and o_Peptostreptococcales_Tissierellales were increased, while 14 negative ion metabolites were upregulated and 21 were downregulated after FZHY treatment. Additionally, 40 positive ion metabolites were upregulated and 63 were downregulated. On the other hand, AST-120 treatment resulted in an increase in the levels of g_Prevotellaceae_NK3B31_group and f_Prevotellaceae, as well as 12 upregulated and 23 downregulated negative ion metabolites and 56 upregulated and 63 downregulated positive ion metabolites. Besides, FZHY increased the levels of candidate bacterial biomarkers that were found to be negatively correlated with some poisonous metabolites, such as 4-hydroxyretinoic acid, and positively correlated with beneficial metabolites, such as l-arginine. AST-120 increased the levels of candidate bacterial biomarkers that were negatively correlated with some toxic metabolites, such as glycoursodeoxycholic acid, 4-ethylphenol, and indole-3-acetic acid. Conclusion: FZHY and AST-120 effectively reduced kidney damage, in which, the recovery of some dysregulated bacteria and metabolites are probably involved. As their mechanisms of regulation were different, FZHY might play a complementary role to AST-120 in treating CKD.

Codonopsis lanceolata polysaccharide ameliorates high-fat diet induced-postpartum hypogalactia via stimulating prolactin receptor-mediated Jak2/Stat5 signaling.

This study aims to investigate the ameliorative effect of Codonopsis lanceolata polysaccharide (PCL) on mice with hypogalatia induced by a high-fat diet (HFD) and the potential underlying mechanism. We found that oral administration of PCL demonstrated significant benefits in countering the negative effects of HFD, including weight gain, hepatic steatosis, mesenteric adipocyte hypertrophy, and abnormal glucose/lipid metabolism. In addition, PCL improved mammary gland development and enhanced lactogenesis performance. Histologically, PCL ameliorated the retardation of ductal growth, reduced mammary fat pad thickness, improved the incomplete linear encapsulation of luminal epithelium and myoepithelium, and increased the proliferation of mammary epithelial cells. Flow cytometry analysis showed that PCL mitigated the detrimental effects of HFD on mammary gland development by promoting the proliferation and differentiation of mammary epithelial cells. Mechanistic studies revealed that PCL upregulated the levels of prolactin (PRL) and its receptor (PRLR) in the mammary gland, activated JAK2/STAT5 signaling pathway, and increased the expression of p63, ERBB4, and NRG1. Overall, PCL can ameliorate HFD-induced hypogalactia by activating PRLR-mediated JAK2/STAT5 signaling. Our findings offer a methodological and theoretical foundation for investigating the functional constituents of traditional Chinese medicine in the treatment of hypogalactia.

Selenium Deficiency Causes Iron Death and Inflammatory Injury Through Oxidative Stress in the Mice Gastric Mucosa.

Selenium (Se) is a trace element essential for the maintenance of normal physiological functions in living organisms. Oxidative stress is a state in which there is an imbalance between oxidative and antioxidant effects in the body. A deficiency of Se can make the body more inclined to oxidation, which can induce related diseases. The aim of this experimental study was to investigate the mechanisms by which Se deficiency affects the digestive system through oxidation. The results showed that Se deficiency treatment led to a decrease in the levels of GPX4 and antioxidant enzymes and an increase in the levels of ROS, MDA, and lipid peroxide (LPO) in the gastric mucosa. Oxidative stress was activated. Triple stimulation of ROS, Fe2+, and LPO induced iron death. The TLR4/NF-κB signaling pathway was activated, inducing an inflammatory response. The expression of the BCL family and caspase family genes was increased, leading to apoptotic cell death. Meanwhile, the RIP3/MLKL signaling pathway was activated, leading to cell necrosis. Taken together, Se deficiency can induce iron death through oxidative stress. Meanwhile, the production of large amounts of ROS activated the TLR4/NF-κB signaling pathway, leading to apoptosis and necrosis of the gastric mucosa.

Purification, structural characteristics and anti-atherosclerosis activity of a novel green tea polysaccharide.

A new homogeneous polysaccharide (TPS3A) was isolated and purified from Tianzhu Xianyue fried green tea by DEAE-52 cellulose and Sephacryl S-500 column chromatography. Structural characterization indicated that TPS3A mainly consisted of arabinose, galactose, galacturonic acid and rhamnose in a molar ratio of 5.84: 4.15: 2.06: 1, with an average molecular weight of 1.596 × 104 kDa. The structure of TPS3A was characterized as a repeating unit consisting of 1,3-Galp, 1,4-Galp, 1,3,6-Galp, 1,3-Araf, 1,5-Araf, 1,2,4-Rhap and 1-GalpA, with two branches on the C6 of 1,3,6-Galp and C2 of 1,2,4-Rhap, respectively. To investigate the preventive effects of TPS3A on atherosclerosis, TPS3A was administered orally to ApoE-deficient (ApoE-/-) mice. Results revealed that TPS3A intervention could effectively delay the atherosclerotic plaque progression, modulate dyslipidemia, and reduce the transformation of vascular smooth muscle cells (VSMCs) from contractile phenotype to synthetic phenotype by activating the expression of contractile marker alpha-smooth muscle actin (α-SMA) and inhibiting the expression of synthetic marker osteopontin (OPN) in high-fat diet-induced ApoE-/- mice. Our findings suggested that TPS3A markedly alleviated atherosclerosis by regulating dyslipidemia and phenotypic transition of VSMCs, and might be used as a novel functional ingredient to promote cardiovascular health.

Structural elucidation of a non-starch polysaccharides from Lilii Bulbus and its protective effects against corticosterone-induced neurotoxicity in PC12 cells.

Lilii Bulbus is a folk medicine for both culinary and medicinal purpose. In traditional medicine theory, Lilii Bulbus is usually used as an complementary therapy for nourishing the heart and lung, clearing heat in the treatment of mental instability and depression. In this study, NLPS-1a (Mw = 2610 Da, DP = 16), a water-soluble non-starch Lilii Bulbus polysaccharides, was isolated and purified. Structural analysis showed that NLPS-1a mainly contained Man and Glc with a molar ratio of 11.137 and 9.427. The glycosidic linkages of NLPS-1a were 1,3-Manp (59.93%), 1,2-Glcp (37.93%), T-Glcp (1.21%) and T-Manp (0.93%), indicating the highly-linear structures. In addition, NLPS-1a could significantly repair the injury of PC12 cells induced by corticosterone (CORT), reduce Lactate dehydrogenase (LDH) leakage and decrease the cell apoptosis in a dose-dependent manner. Above all, the results indicated that NLPS-1a had protective effects against CORT-induced neurotoxicity in PC12 cells, and might be a natural antidepressant, which enriched the study of the metabolic mechanism between herbal polysaccharides and antidepressant.

Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson's disease after dietary supplementation with branched-chain amino acids.

The gut microbiota and microbial metabolites influence the enteric nervous system and the central nervous system via the microbial-gut-brain axis. Increasing body of evidence suggests that disturbances in the metabolism of peripheral branched-chain amino acids (BCAAs) can contribute to the development of neurodegenerative diseases through neuroinflammatory signaling. Preliminary research has shown that longitudinal changes in serum amino acid levels in mouse models of Parkinson's disease (PD) are negatively correlated with disease progression. Therefore, the aim of the present study was to determine the changes in serum levels of short-chain fatty acids (SCFAs) in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD after dietary BCAA supplementation. In our research, gas chromatography-mass spectrometry was used to detect serum SCFA concentrations. The data were then analyzed with principal component analysis and orthogonal partial least squares discriminant analysis. Finally, the correlations of serum SCFA levels with gut and motor function in MPTP-induced PD mice were explored. Propionic acid, acetic acid, butyric acid, and isobutyric acid concentrations were elevated in MPTP + H-BCAA mice compared with MPTP mice. Propionic acid concentration was increased the most, while the isovaleric acid concentration was decreased. Propionic acid concentration was positively correlated with fecal weight and water content and negatively correlated with the pole-climbing duration. In conclusion, these results not only suggest that propionic acid may be a potential biomarker for PD, but also indicate the possibility that PD may be treated by altering circulating levels of SCFA.

Panax Notoginseng Saponins Alleviate LPS-induced Fibrosis of HK-2 Cells by Inhibiting the Activation of NLRP3 Inflammasome and Pyroptosis.

BACKGROUND: Renal fibrosis is related to impaired kidney function and can eventually lead to end-stage renal disease, for which no effective treatment is available. Panax notoginseng saponins (PNS), as a commonly used traditional Chinese medicine, is considered a possible alternative for the treatment of fibrosis. OBJECTIVE: The purpose of the present study was to investigate the effects and possible mechanisms of PNS on renal fibrosis. METHODS: HK-2 cells were used to induce renal fibrosis cell model by lipopolysaccharide (LPS), and the cytotoxicity of PNS on HK-2 cells was investigated. Cell damage, pyroptosis, and fibrosis were analyzed to investigate the effects of PNS on LPS-induced HK-2 cells. NLRP3 agonist Nigericin was used further to explore the inhibitory effect of PNS on LPS-induced pyroptosis so as to clarify the possible mechanism of PNS on renal fibrosis. RESULTS: PNS had no cytotoxicity on HK-2 cells, and could reduce the apoptosis and the release of lactate dehydrogenase (LDH) and inflammatory cytokines of LPS-induced HK-2 cells, showing an alleviating effect on cell damage. PNS also reduced the expression of pyroptosis proteins NLRP3, IL-1ß, IL-18, and Caspase-1, as well as fibrosis proteins α-SMA, collagen Ⅰ and p-Smad3/Smad3, which showed an inhibitory effect on LPS-induced pyroptosis and fibrosis. In addition, LPS-induced cell damage, pyroptosis, and fibrosis were aggravated after Nigericin treatment, while PNS alleviated the aggravation caused by Nigericin. CONCLUSION: PNS inhibits pyroptosis by inhibiting the activation of NLRP3 inflammasome in LPS-induced HK-2 cells, which ultimately alleviates renal fibrosis and plays a good role in the treatment of kidney diseases.

Using a Multi-isotope Approach and Isotope Mixing Models to Trace and Quantify Phosphorus Sources in the Tuojiang River, Southwest China.

Identifying phosphorus (P) sources is critical for solving eutrophication and controlling P in aquatic environments. Phosphate oxygen isotopes (δ18Op) have been used to trace P sources. However, the application of this method has been greatly restricted due to δ18OP values from the potential source having wide and overlapping ranges. In this research, P sources were traced by combining δ18Op with multiple stable isotopes of nitrogen (δ15N), hydrogen (δD), and dissolved inorganic carbon (δ13C). Then, a Bayesian-based Stable Isotope Analysis in R (SIAR) model and IsoSource model were used to estimate the proportional contributions of the potential sources in the Tuojiang River. δ18Op was not in equilibrium with ambient water, and statistically significant differences in the δ18Op values were found between the potential sources, indicating that δ18Op can be used to trace the P sources. δ15N, δD, and δ13C could assist δ18Op in identifying the main sources of P. The SIAR and IsoSource models suggested that industrial and domestic sewage was the largest contributor, followed by phosphate rock and phosphogypsum and agricultural sewage. The uncertainty of the calculation results of the SIAR model was lower than that of the IsoSource model. These findings provide new insights into tracing P sources using multiple stable isotopes in watersheds.

Taurine promotes B-cell activation by interaction with the VH /VL framework regions of B-cell receptor.

Taurine (Tau) is a special sulphur-containing amino acid and has been widely used as a dietary supplement. Although Tau exists in lymphocytes in large quantities, the physiological significance of Tau to modulate human immunity is unknown. In the present study, we first found that Tau regulates the B-cell receptor (BCR)-mediated signal transduction and induces the B cells activation. The IgG production of mice after ovalbumin immunization was also increased by Tau administration. Moreover, the isothermal titration calorimetry and surface plasmon resonance analysis have shown that Tau specifically bound to the IgG2a-BCR. The Tau could bind to IgG F(ab')2 regions via fluorescence spectroscopy analysis. In the molecular docking analysis, Tau bound to the framework regions (FRs) of variable region of the heavy chains (VH ) and in the light chains (VL ) of IgG2a-BCR. Our results suggested that Tau could improve the activation of B cells by interaction with the VH /VL FRs of BCR.

Berberine Depresses Inflammation and Adjusts Smooth Muscle to Ameliorate Ulcerative Colitis of Cats by Regulating Gut Microbiota.

Intestinal microbiota dysbiosis is a well established characteristic of ulcerative colitis (UC). Regulating the gut microbiota is an effective UC treatment strategy. Berberine (BBR), an alkaloid extracted from several Chinese herbs, is a common traditional Chinese medicine. To establish the efficacy and mechanism of action of BBR, we constructed a UC model using healthy adult shorthair cats to conduct a systematic study of colonic tissue pathology, inflammatory factor expression, and gut microbiota structure. We investigated the therapeutic capacity of BBR for regulating the gut microbiota and thus work against UC in cats using 16S rRNA genes amplicon sequencing technology. Our results revealed that dextran sulfate sodium (DSS)-induced cat models of UC showed weight loss, diarrhea accompanied by mucous and blood, histological abnormalities, and shortening of the colon, all of which were significantly alleviated by supplementation with BBR. A 16S rRNA gene-based microbiota analysis demonstrated that BBR could significantly benefit gut microbiota. Western blot, quantitative PCR, and enzyme-linked immunosorbent assays (ELISAs) showed that in DSS-induced cat models, the expression of the inflammatory factors was increased, activating the JAK2/STAT3 signaling pathway, and treatment with BBR reversed this effect. The myosin light chain (MLC) phosphorylation in the smooth muscle of the intestines is associated with motility of inflammation-related diarrhea in cats. This study used gut flora analyses to demonstrate the anti-UC effects of BBR and its potential therapeutic mechanisms and offers novel insights into the prevention of inflammatory diseases using natural products. IMPORTANCE Ulcerative colitis (UC) is common in clinics. Intestinal microbiota disorder is correlated with ulcerative colitis. Although there are many studies on ulcerative colitis in rats, there are few studies on colitis in cats. Therefore, this study explored the possibility of the use of BBR as a safe and efficient treatment for colitis in cats. The results demonstrated the therapeutic effects of BBR on UC based on the state of the intestinal flora. The study found BBR supplementation to be effective against dextran sulfate sodium (DSS)-induced colitis, smooth muscle damage, and gut microbiota dysbiosis.

Utilization of Soybean Oil Waste for a High-Level Production of Ceramide by a Novel Phospholipase C as an Environmentally Friendly Process.

Ceramide is a natural functional ingredient as food additive and medicine that has attracted extensive attention in the food, medical, and cosmetic industries. Here, we developed a biotechnological strategy based on a recombinant whole-cell biocatalyst for efficiently producing ceramide from crude soybean oil sediment (CSOS) waste. A novel phospholipase C (PLCac) from Acinetobacter calcoaceticus isolated from soil samples was identified and characterized. Furthermore, recombinant Komagataella phaffii displaying PLCac (dPLCac) on the cell surface was constructed as a whole-cell biocatalyst with better thermostability (30-60 °C) and pH stability (8.0-10.0) to successfully produce ceramide. After synergistical optimization of reaction time and dPLCac dose, the ceramide yield of hydrolyzing from CSOS using dPLCac was 51% (the theoretical maximum yield of converting sphingomyelin, ∼70%) and the relative yield was over 50% after seven consecutive 4 h batches under the optimized conditions. Our study provides a potentially promising strategy for the commercial production of ceramide.

Polygonatum cyrtonema Hua polysaccharide exhibits anti-fatigue activity via regulating osteocalcin signaling.

In the present study, we explored the anti-fatigue activity and its potential mechanism of a purified Polygonatum cyrtonema polysaccharide (PCP) on mice using weight-loaded swimming test. Results showed that PCP remarkably prolonged the exhaustive swimming time of mice when compared with normal control group. Meanwhile, PCP decreased serum levels of lactic acid (LA), blood uric nitrogen (BUN), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA), and increased the contents of liver glycogen, muscle glycogen and muscle ATP. These results revealed that PCP had good anti-fatigue ability. The histomorphologic analysis showed that PCP increased the cross-section area of the muscle fibers. Furthermore, PCP significantly enhanced the protein levels of bone morphogenetic protein-2 (BMP-2), phosphor-Smad1, Runt-related transcription factor 2 (Runx2) and osteocalcin (OC) in skeleton. Similar variation was also observed in the expression of osteocalcin signaling mediators of phosphorylated cAMP-response element binding protein (p-CREB) and phosphorylated hormone-sensitive lipase (p-HSL) in skeletal muscle. These results suggested that PCP resisted fatigue possibly via regulating osteocalcin signaling.

Vitamins and Helicobacter pylori: An Updated Comprehensive Meta-Analysis and Systematic Review.

BACKGROUND: Over recent decades, epidemiological studies have shown relationships between vitamins and Helicobacter pylori (H. pylori) infection and eradication, but the results are controversial. METHODS: A comprehensive meta-analysis and systematic review were conducted to clarify the relationships between common types of vitamins and H. pylori. We applied meta-regression, subgroup analysis and sensitivity analysis to obtain available evidence. Articles published from January 1991 to June 2021 in PubMed, EMBASE, and the Cochrane Library were searched. RESULTS: In total, we identified 48 studies. The results indicate that H. pylori -positive patients had lower serum vitamin B12 [standardized mean difference (SMD) = -0.30; 95% confidence interval (CI): -0.53 - -0.08], folate (SMD = -0.69; 95% CI: -1.34 - -0.04), vitamin C (SMD = -0.37; 95%CI: -0.57 - -0.18) and vitamin D (SMD = -0.34; 95% CI: -0.49 - -0.18) levels than H. pylori-negative patients. Patients in which H. pylori had been successfully eradicated had higher serum vitamin D levels (SMD = 1.37; 95% CI: 0.37-2.38) than in patients in which eradication had been unsuccessful. The serum vitamin B12 levels of H. pylori-positive patients improved after successful H. pylori eradication therapy (SMD = 1.85; 95% CI: 0.81-2.90), and antioxidant vitamin supplementation to an H. pylori eradication regimen improved the eradication rate (risk ratio = 1.22; 95% CI: 1.02-1.44 for per-protocol analysis; risk ratio = 1.25; 95% CI: 1.06-1.47 for intention-to-treat analysis). CONCLUSIONS: H. pylori infections decrease the serum levels of several types of vitamins, eradication of H. pylori could rescue its adverse effects, and antioxidant vitamin supplementation may improve the H. pylori eradication rate. SYSTEMATIC REVIEW REGISTRATION: identifier: CRD42021268127.

Study on the Release Potential of BPA and Steroid Estrogens in the Sediments of Erhai Lake, a Typical Plateau Lake of China.

On-site sampling analysis and laboratory-scale experiments were conducted to study the pollution status and release potential of EDCs in Erhai Lake. We found that nitrogen and phosphorus pollution in Erhai Lake sediment were both at a high level, as well as EDCs pollution. The concentrations of BPA, E2α, E1, E2ß, EE2, and E3 were 36.84 ng/g(DW), 13.04 ng/g(DW), 128.97 ng/g(DW), 52.57 ng/g(DW), 18.48 ng/g(DW) and 5.36 ng/g(DW), respectively. The concentrations of E2α, E1, E2ß and EE2 in the bottom water were higher than the surface water due to the impact of sediment release. The results of the 20 days release test indicated that BPA release from the sediment had a greater correlation with the original concentration and the particle size of sediment, while the steroid EDCs had no obvious correlation with these two factors, probably due to the difference in hydrophobicity between them. Under hydraulic disturbance and aerobic conditions, the release process of EDCs was accompanied by a large amount of microbial degradation, and degradation amount > released amount. BPA was released quickly, 9.56% was released in 20 days, but only 3.37% of steroid EDCs released. In comparison, the release process of steroids was longer and posed a greater threat to aquatic ecology.

Integration of Marine Macroalgae (Chaetomorpha maxima) with a Moving Bed Bioreactor for Nutrient Removal from Maricultural Wastewater.

Rather than direct nutrient removal from wastewaters, an alternative approach aimed at nutrient recovery from aquacultural wastewaters could enable sustainable management for aquaculture production. This study demonstrated the feasibility of cultivating marine macroalgae (Chaetomorpha maxima) with a moving bed bioreactor (MBBR-MA), to remove nitrogen and phosphorus in aquaculture wastewater as well as to produce macroalgae biomass. MBBR-MA significantly increased the simultaneous removal of nitrate and phosphate in comparison with only MBBR, resulting in an average total nitrogen (TN) and total phosphorus (TP) removal efficiency of 42.8 ± 5.5% and 83.7 ± 7.7%, respectively, in MBBR-MA while MBBR had no capacity for TN and TP removal. No chemical oxygen demand (COD) removal was detected in both reactors. Phosphorus could be a limiting factor for nitrogen uptake when N : P ratio increased. The recovered nitrogen and phosphorus resulted in a specific growth rate of 3.86%-10.35%/day for C. maxima with an uptake N : P ratio of 6. The presence of macroalgae changed the microbial community in both the biofilter and water by decreasing the relative abundance of Proteobacteria and Nitrospirae and increasing the abundance of Bacteroidetes. These findings indicate that the integration of the macroalgae C. maxima with MBBR could represent an effective wastewater treatment option, especially for marine recirculating aquaculture systems.

Cordycepin inhibits pancreatic cancer cell growth in vitro and in vivo via targeting FGFR2 and blocking ERK signaling.

Cordycepin (3'-deoxyadenosine) from Cordyceps militaris has been reported to have anti-tumor effects. However, the molecular target and mechanism underlying cordycepin impeding pancreatic cancer cell growth in vitro and in vivo remain vague. In this study, we reported functional target molecule of cordycepin which inhibited pancreatic cancer cells growth in vitro and in vivo. Cordycepin was confirmed to induce apoptosis by activating caspase-3, caspase-9 and cytochrome c. Further studies suggested that MAPK pathway was blocked by cordycepin via inhibiting the expression of Ras and the phosphorylation of Erk. Moreover, cordycepin caused S-phase arrest and DNA damage associated with activating Chk2 (checkpoint kinase 2) pathway and downregulating cyclin A2 and CDK2 phosphorylation. Very interestingly, we showed that cordycepin could bind to FGFR2 (KD = 7.77 × 10-9) very potently to inhibit pancreatic cancer cells growth by blocking Ras/ErK pathway. These results suggest that cordycepin could potentially be a leading compound which targeted FGFR2 to inhibit pancreatic cells growth by inducing cell apoptosis and causing cell cycle arrest via blocking FGFR/Ras/ERK signaling for anti-pancreatic cancer new drug development.

A prospective, crossover randomized trial of the optimal timing for leucovorin rescue after high-dose methotrexate management in adult non-Hodgkin's lymphoma patients.

This study aimed to investigate the optimal time of leucovorin rescue for HDMTX in non-Hodgkin's lymphoma (NHL) patients. Ninety-eight patients treated with HDMTX were randomly assigned to receive leucovorin at either 18 or 24 h after initiation of HDMTX infusion during the first cycle and switched to the other mode in the second cycle. All courses achieved an efficacious MTX concentration. Compared to the 18th hour group, the 24th hour group exhibited an increase in incidence of thrombocytopenia (48% versus 34.7%, p = .036) and grade III/IV neutropenia (34.7% versus 21.4%, p = .039). No bleeding occurred and the incidence of fever with grade III/IV neutropenia was low with no difference observed between the two groups. We recommend that with the HDMTX generally used most adult patients with NHL may have greater therapeutic benefit and acceptable toxicity with their LV rescue started at 24 h instead of 18 h.

Homogenized halides and alkali cation segregation in alloyed organic-inorganic perovskites.

The role of the alkali metal cations in halide perovskite solar cells is not well understood. Using synchrotron-based nano-x-ray fluorescence and complementary measurements, we found that the halide distribution becomes homogenized upon addition of cesium iodide, either alone or with rubidium iodide, for substoichiometric, stoichiometric, and overstoichiometric preparations, where the lead halide is varied with respect to organic halide precursors. Halide homogenization coincides with long-lived charge carrier decays, spatially homogeneous carrier dynamics (as visualized by ultrafast microscopy), and improved photovoltaic device performance. We found that rubidium and potassium phase-segregate in highly concentrated clusters. Alkali metals are beneficial at low concentrations, where they homogenize the halide distribution, but at higher concentrations, they form recombination-active second-phase clusters.

Laminaria japonica Polysaccharide Inhibits Vascular Calcification via Preventing Osteoblastic Differentiation of Vascular Smooth Muscle Cells.

This study aimed to investigate the effect and underlying mechanism of a purified Laminaria japonica polysaccharide (LJP61A) on preventing vascular calcification (VC). In the adenine-induced chronic renal failure (CRF) mice VC model and the ß-glycerophosphate (ß-GP)-induced vascular smooth muscle cells (VSMC) calcification model, LJP61A was found to significantly inhibit VC phenotypes as determined by biochemical analysis and von Kossa, alizarin red, and immunohistochemical staining. Meanwhile, LJP61A remarkably up-regulated the mRNA levels of VSMC related markers and down-regulated the mRNA levels of sodium-dependent phosphate cotransporter Pit-1. In addition, LJP61A could significantly decrease the protein levels of core-binding factor-1, osteocalcin, bone morphogenetic protein 2, and receptor activator for nuclear factor-κB ligand, and it can increase the protein levels of osteoprotegerin and matrix gla protein. These results indicated that LJP61A ameliorated VC both in vivo and in vitro via preventing osteoblastic differentiation of VSMC, suggesting LJP61A might be a potential therapeutic agent for VC in CRF patients.