Potential antioxidative components from Syringa oblata Lindl stems revealed by affinity ultrafiltration with multiple drug targets.

Traditional Chinese medicine is the main source of natural products due to its remarkable clinical efficacy. Syringa oblata Lindl (S. oblata) was widely used because of its extensive biological activities. However, to explore the antioxidant components of S. oblata against tyrosinase, the experiments of antioxidation in vitro were employed. At the same time, the determination of TPC was also use to assess the antioxidant ability of CE, MC, EA and WA fractions and the liver protective activity of the EA fraction was evaluated by mice in vivo. Next, UF-LC-MS technology was performed to screen and identify the efficient tyrosinase inhibitors in S. oblata. The results showed that alashinol (G), dihydrocubebin, syripinin E and secoisolariciresinol were characterized as potential tyrosinase ligands and their RBA values were 2.35, 1.97, 1.91 and 1.61, respectively. Moreover, these four ligands can effectively dock with tyrosinase molecules, with binding energies (BEs) ranging from 0.74 to -0.73 kcal/mol. In addition, tyrosinase inhibition experiment was employed to evaluate the tyrosinase inhibition activities of four potential ligands, the result showed that compound 12 (alashinol G, IC50 = 0.91 ± 0.20 mM) showed the strongest activity to tyrosinase, followed by secoisolariciresinol (IC50 = 0.99 ± 0.07 mM), dihydrocubebin (IC50 = 1.04 ± 0.30 mM) and syripinin E (IC50 = 1.28 ± 0.23 mM), respectively. The results demonstrate that S. oblata might have excellent antioxidant activity, and UF-LC-MS technique is a effective means to filter out tyrosinase inhibitors from natural products.

Jian-Pi-Yi-Shen formula restores iron metabolism from dysregulation in anemic rats with adenine-induced nephropathy.

ETHNOPHARMACOLOGICAL RELEVANCE: Jian-Pi-Yi-Shen (JPYS) is a herbal decoction being used to relieve the symptoms of chronic kidney disease (CKD) and its complications, including anemia, for over twenty years. Nonetheless, it is unclear how JPYS influences renal anemia and iron metabolism. AIM OF THE STUDY: An analysis of network pharmacology, chemical profiling, and in vivo experiments was conducted to identify the impact of JPYS on JAK2-STAT3 pathway and iron utilization in renal anemia and CKD. MATERIALS AND METHODS: The chemical properties of JPYS and its exposed ingredients were detected in vivo. And based on the aforesaid chemical compounds, the potential targets and signaling pathways of JPYS for renal anemia treatment were predicted by network pharmacology. Afterward, an adenine-feeding animal model of CKD-related anemia was developed to verify the mechanism by which JPYS modulates iron recycling to treat renal anemia. Renal injury was estimated by serum creatinine (Scr), blood urea nitrogen (BUN), histopathological examinations and fibrosis degree. Western blot, enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry approaches were utilized to assess the levels of JAK2, STAT3 and iron metabolism-related factors. RESULTS: There were 164 active ingredients identified in JPYS, including prototypes and metabolites in vivo were identified in JPYS, and 21 core targets were found through network pharmacology based on topological characteristics. Combined with the core targets and pathway enrichment analysis, the majority of the candidate targets were associated with the JAK2-STAT3 signaling pathways. Experimental results indicated that JPYS treatment significantly decreased the expression of BUN and Scr, restored renal pathological damage, down-regulated fibrosis degree, and improved hematological parameters such as red blood cell, hemoglobin and hematocrit in CKD rats. Furthermore, JPYS significantly restored iron metabolism from dysregulation by increasing the levels of iron and ferritin in the serum, inhibiting the production of hepcidin in liver and serum, and regulating transferrin receptor 1 in bone marrow. Meanwhile, the expression of JAK2 and STAT3 was suppressed by JPYS treatment. CONCLUSIONS: Based on these results, JPYS reduces hepcidin levels by inhibiting the activation of JAK2-STAT3 signaling, thereby protecting against iron deficiency anemia.

Occurrence and sources of microplastics and polycyclic aromatic hydrocarbons in surface sediments of Svalbard, Arctic.

Due to the distinct environment condition and geographic location, Svalbard has been recognized as a potential pollution reservoir in the Arctic. In this study, 8 surface sediment samples were collected from two fjords in Svalbard (Kongsfjorden and Rijpfjorden) in 2017, and they were searched for microplastics and polycyclic aromatic hydrocarbons (PAHs). PAHs were also investigated in 10 soil samples of Ny-Ålesund for local anthropogenic source analysis. The level of microplastics and other anthropogenic particles ranged from not detected (ND) to 4.936 particles/kg dry weight (DW). Fiber was the only shape of the microplastics found and three polymers (polyester, rayon and cellulose) were detected, which suggested that fisheries-related debris and textile materials were possible sources of microplastics and anthropogenic particles. For PAHs, the level of ∑26PAH was 9.2 ng/g to 67.1 ng/g (DW), and were dominated by lnP and BghiP, indicating petroleum combustion source. Further analysis revealed that traffic emissions from cars and diesel combustion from a local power plant were major sources of PAHs in soils of Ny-Alesund, while traffic emissions from ships were the dominate source of PAHs in sediments of Kongsfjorden and Rijpfjorden. A higher level of PAHs was observed in Ny-Alesund, confirming an anthropogenic input, while transport via ocean currents might contribute to the higher abundance of microplastics in Rijpfjorden. Further research and even long-term observation of pollutants are needed to fully understand the pollution status in polar regions.

Therapeutic carrier based on solanesol and hyaluronate for synergistic tumor treatment.

The administration of nanodrugs can lead to metabolism related systemic toxicity due to the use of inert carriers in large quantities. Carrier materials that offer therapeutic effects are therefore a promising means of addressing this limitation. Herein, a hyaluronate-based nanocarrier was prepared from hyaluronic acid (HA) and solanesol. Solanesyl thiosalicylate (STS) derived from solanesol has certain antitumor effects and was used to modify HA. The conjugate (HA-STS) self-assembled into nanoparticles acting as a drug carrier. The synthesis of the conjugates was confirmed by 1H NMR spectroscopy. Doxorubicin (DOX) was loaded into the HA-STS nanoparticles with a relatively high content of 6.0%. pH-sensitive drug release behavior was achieved by introducing a hydroazone bond between STS and HA. A cytotoxicity assay indicated that the blank nanoparticles had an antitumor effect, which was enhanced by loading with an additional drug. Moreover, in vivo antitumor experiments indicated that the HA-STS-DOX showed superior tumor inhibition compared with free DOX, as well as lower cardiotoxicity and hepatotoxicity, demonstrating the advantages of the bioactive drug vehicles in cancer therapy.

Zinc uptake and replenishment mechanisms during repeated phytoextraction using Sedum plumbizincicola revealed by stable isotope fractionation.

Improving phytoremediation techniques requires a thorough understanding of the mechanisms of plant uptake and the replenishment of the bioavailable pool of the target element, and this may be effectively explored using stable isotope methods. A repeated phytoextraction experiment over five successive crops of cadmium (Cd) and zinc (Zn) hyperaccumulator Sedum plumbizincicola X.H. Guo et S.B. Zhou ex L.H. Wu (Crassulaceae) was conducted using four agricultural soils differing in soil pH and clay content. The isotopic composition of total Zn and NH4OAc-extractable Zn in soils before phytoextraction and after the fifth crop were determined, together with Zn in shoot samples in the first crop. S. plumbizincicola preferentially took up light Zn isotopes from the NH4OAc-extractable pool (Δ66Znshoot-extract = -0.42 to -0.16‰), indicating the predominance of Zn low-affinity transport. However, after long-term phytoextraction NH4OAc-extractable Zn became isotopically lighter than prior to phytoextraction in three of the soils (Δ66Znextract: P5-P0 = -0.39 to -0.10‰). This was resulted from the equilibrium replenishment of Zn bound to iron (Fe) and manganese (Mn) oxides based on Zn isotopic and chemical speciation analysis. Zinc showed opposite fractionation patterns to Cd in the same plant-soil system with heavy Cd isotope enrichment in S. plumbizincicola (Δ114/110Cdshoot-extract = 0.02-0.17‰) and in the NH4OAc-extractable pool after repeated phytoextraction (Δ114/110Cdextract: P5-P0 = 0.07-0.18‰). This indicates different mechanisms of membrane transport (high-affinity transport of Cd) and supplementation of the bioavailable pool in soil (Cd supplied mainly through complexation with root-derived organic ligands) of the two metals. The combination of chemical speciation and stable Zn isotope ratios in the plant and the bioavailable soil pool reveal that the Zn pool related to Fe and Mn oxides became increasingly bioavailable with increasing crop generations. Capsule: Stable isotope analysis indicates that soil Fe- and Mn-oxide bound Zn replenishment boosted Zn uptake by the hyperaccumulator Sedum plumbizincicola during long-term remediation.

The expression of mimecan in adrenal tissue plays a role in an organism's responses to stress.

Mimecan encodes a secretory protein that is secreted into the human serum as two mature proteins with molecular masses of 25 and 12 kDa. We found 12-kDa mimecan to be a novel satiety hormone mediated by the upregulation of the expression of interleukin (IL)-1ß and IL-6 in the hypothalamus. Mimecan was found to be expressed in human pituitary corticotroph cells and was up-regulated by glucocorticoids, while the secretion of adrenocorticotropic hormone (ACTH) in pituitary corticotroph AtT-20 cells was induced by mimecan. However, the effects of mimecan in adrenal tissue on the hypothalamic-pituitary-adrenal (HPA) axis functions remain unknown. We demonstrated that the expression of mimecan in adrenal tissues is significantly downregulated by hypoglycemia and scalded stress. It was down-regulated by ACTH, but upregulated by glucocorticoids through in vivo and in vitro studies. We further found that 12-kDa mimecan fused protein increased the corticosterone secretion of adrenal cells in vivo and in vitro. Interestingly, compared to litter-mate mice, the diurnal rhythm of corticosterone secretion was disrupted under basal conditions, and the response to restraint stress was stronger in mimecan knockout mice. These findings suggest that mimecan stimulates corticosterone secretion in the adrenal tissues under basal conditions; however, the down-regulated expression of mimecan by increased ACTH secretion after stress in adrenal tissues might play a role in maintaining the homeostasis of an organism's responses to stress.

Intravenous immunoglobulin G in the treatment of ABO hemolytic disease of the newborn during the early neonatal period at a tertiary academic hospital: a retrospective study.

OBJECTIVE: To evaluate the efficacy and safety of intravenous immunoglobulin G (IVIG) in infants with ABO hemolytic disease of the newborn (HDN). METHODS: Infants with moderate-to-severe ABO HDN during early neonatal period (<7 days) at our hospital in 2017 were included in this retrospective study. Patients treated with IVIG and phototherapy were classified as the IVIG group, and those who only received phototherapy were classified as the phototherapy only group. RESULTS: Forty-six patients were classified into the IVIG group and 68 other patients were classified into the phototherapy only group. There was no significant difference in duration of phototherapy, hospitalization periods, needs for exchange transfusion, transfusions, and incidence of bilirubin-induced neurological sequelae between these two groups (P = 0.20, 0.27, 0.65, 0.47, 0.78, respectively). CONCLUSION: It seems unnecessary to expose neonates to IVIG in moderate-to-severe ABO HDN when the available data show no appreciable benefits.

Jian-Pi-Yi-Shen Regulates EPO and Iron Recycling Protein Expressions in Anemic Rats with Chronic Kidney Disease: Accumulation of Hypoxia Inducible Factor-2α via ERK Signaling.

Jian-Pi-Yi-Shen (JPYS), the traditional Chinese medicine (TCM) decoction, has been commonly used to treat chronic kidney disease (CKD) and its complications such as anemia. JPYS has been previously found to induce erythropoietin (EPO) production in HEK293T cells and CKD rats. However, the mechanism of JPYS in treating anemia of CKD rats has remained largely unknown. Here, we further extend our effort to investigate the translational control of hypoxia inducible factor- (HIF-) α protein via ERK signaling and the effect on iron recycling-related protein expression by JPYS, thus revealing the mechanism of JPYS in correcting anemia in CKD. Experimental CKD rats with anemia were induced by 5/6 nephrectomy. Rats were administrated orally with high dose (6.0 g/kg/d) and low dose (1.5 g/kg/d) of JPYS for 90 days. Serum hepcidin level was determined to evaluate iron homeostasis. The protein expressions of HIF-2α, erythropoietin (EPO), ferritin, and ferroportin (FPN) and the phosphorylation level of extracellular signal-regulated kinase 1/2 (ERK1/2) were detected by Western blot. The results showed that JPYS treatment significantly ameliorated kidney function by reducing increased levels of blood urea nitrogen (BUN), serum creatinine (Scr), and urine protein (UPRO). Periodic acid-Schiff (PAS) and Masson staining observation showed that the renal pathological damage was restored in JPYS-treated CKD rats. In parallel, JPYS markedly improved CKD anemia through upregulation of red blood cell (RBC), hemoglobin (HGB), and hematocrit (HCT). JPYS stimulated EPO and HIF-2α protein expressions in both the kidney and liver of CKD rats. Furthermore, JPYS induced the phosphorylation of ERK1/2 protein. In addition, JPYS regulated protein expression of ferritin and FPN in both the liver and spleen of CKD rats and the serum level of hepcidin. In conclusion, JPYS induces the expression of EPO through ERK-mediated HIF-2α protein accumulation and regulates systemic iron recycling, supporting its role in promoting erythropoiesis and improvement of anemia in CKD.

Effect of pectin oligosaccharides and zinc chelate on growth performance, zinc status, antioxidant ability, intestinal morphology and short-chain fatty acids in broilers.

A 42-day trial was conducted to investigate the effect of pectin oligosaccharides (POS) and zinc chelate (Zn-POS) on growth performance, antioxidant ability, zinc status, intestinal morphology and short-chain fatty acids in broilers. A total of 324 1-day-old Arbor Acres broilers were randomly assigned to three treatments with six cages of 18 chicks. Treatments were: (a) Control, 80 mg/kg Zn from ZnSO4 ; (b) POS, 80 mg/kg Zn from ZnSO4 + 482 mg/kg POS (the same amount of POS as treatment 3); and (c) Zn-POS, 80 mg/kg zinc from Zn-POS. Compared to the Control, both POS and Zn-POS supplementation increased average daily gain and reduced the mortality during day 22-42, and only Zn-POS supplementation decreased the ratio of feed to gain during day 22-42 and 1-42. Moreover, both POS and Zn-POS supplementation improved Zn status and gut function as evidenced by increased metallothionein concentrations in the pancreas, villus height in the duodenum and isobutyrate concentrations in the caecal digesta. Additionally, Zn-POS supplementation increased gene expressions of metallothionein, Zn transporter 1, Zn transporter 2 in the pancreas, nuclear factor erythroid 2-related factor 2 in the liver, the concentrations of acetate, propionate, butyrate and total SCFA in the caecal digesta and the villus height to crypt depth ratio in the duodenum and jejunum, whereas decreased the crypt depth in these two tissues. Altogether, our results revealed that dietary POS or Zn-POS supplementation benefited growth performance, Zn status, antioxidant ability and gut function of broilers. Supplementing Zn-POS in the form of chelate was more effective than feeding POS or ZnSO4 separately.

Antisense RNA-Based Strategy for Enhancing Surfactin Production in Bacillus subtilis TS1726 via Overexpression of the Unconventional Biotin Carboxylase II To Enhance ACCase Activity.

The antisense RNA (asRNA) strategy is commonly used to block protein expression and downregulate the contents of metabolites in several microorganisms. Here, we show that the asRNA strategy can also be used to block gfp expression in Bacillus subtilis TS1726, which could further be utilized in the identification of new genes and functions. Via application of this strategy, biotin carboxylase II encoded by yngH (GeneID 939474) was identified to play a more significant role in maintaining acetyl-CoA carboxylase (ACCase) activity and enhancing surfactin synthesis compared to those of other ACCase subunits. The yngH gene was then overexpressed in the engineered strain B. subtilis TS1726(yngH). The surfactin titer of TS1726(yngH) increased to 13.37 g/L in a flask culture, representing a 43% increase compared to that of parental strain TS1726. This strategy opens the door to achieving large-scale production and broad application of surfactin.

Effects of Dietary Zinc Pectin Oligosaccharides Chelate Supplementation on Growth Performance, Nutrient Digestibility and Tissue Zinc Concentrations of Broilers.

The experiment was conducted to investigate the effects of zinc pectin oligosaccharides (Zn-POS) chelate on growth performance, nutrient digestibility, and tissue zinc concentrations of Arbor Acre broilers aged from 1 to 42 days. A total of 576 1-day-old broilers were randomly assigned into 4 groups with 9 replicates per group and 16 chicks per replicate. Chicks were fed either a basal diet (control) or basal diet supplemented with Zn-POS at 300 (Zn-POS-300), 600 (Zn-POS-600), or 900 mg/kg (Zn-POS-900), respectively, for 42 days. A 3-day metabolism trial was conducted during the last week of the experiment feeding. The average daily gain and the average daily feed intake of Zn-POS-600 were significantly higher (P < 0.05) than those of either the control, Zn-POS-300, or Zn-POS-900. Zn-POS-600 had the highest apparent digestibility of dry matter, crude protein, and metabolic energy among all groups. The control group had the lowest apparent digestibility of dry matter (P < 0.05), whereas the apparent digestibility of dry matter in Zn-POS-600 was higher (P < 0.05) than that of Zn-POS-300. The apparent digestibility of crude protein in Zn-POS-600 or Zn-POS-900 was higher (P < 0.05) compared to Zn-POS-300 or the control. The apparent digestibility of metabolic energy in Zn-POS-600 or Zn-POS-900 was higher (P < 0.05) than that of Zn-POS-300. Zn-POS-600 had the highest liver zinc concentrations (P < 0.05), while Zn-POS-900 had the highest pancreatic zinc concentrations (P < 0.05). Our data suggest that the supplementation of 600 mg/kg Zn-POS is optimal in improving the average daily gain and the average daily feed intake, utilization of dietary dry matter and crude protein, and increasing tissue zinc concentrations in liver and pancreas of broilers.

Neuroprotection against Aß25-35-induced apoptosis by Salvia miltiorrhiza extract in SH-SY5Y cells.

The neurotoxicity of ß-amyloid protein (Aß) contributes significantly to the pathogenesis of Alzheimer's disease (AD), and hence the attractive therapeutic strategies focusing on the modulation of Aß-induced neurotoxicity are warranted. The present study aims to investigate the neuroprotection and underlying mechanisms by which Salvia miltiorrhiza Bunge (Lamiaceae) extract (SME) protects against Aß25-35-induced apoptosis in SH-SY5Y cells. 2h Pre-treatment of SH-SY5Y cells with SME (0.01, 0.1 or 0.2mg raw herb/ml) concentration-dependently attenuated Aß25-35-induced cell death, as evidenced by the increase in cell viability and decrease in neuronal apoptosis. In addition, SME suppressed the increased intracellular reactive oxygen species levels, decreased the protein expression of cleaved caspase-3, cytosolic cytochrome c, and Bax/Bcl-2 ratio. These findings taken together suggest that SME provides substantial neuroprotection against Aß25-35-induced neurotoxicity in SH-SY5Y cells, at least in part, via inhibiting oxidative stress and attenuating the mitochondria-dependent apoptotic pathway. The approach used in this study may also be useful for the screening of therapeutic agents for AD and other related neurodegenerative disease.

[Neuroprotective effects of water extracts of American Ginseng on SH-SY5Y cells apoptosis induced by Abeta25-35].

OBJECTIVE: To study the neuroprotective effect of water extracts of American Ginseng (WEAG) on Abeta25-35-induced SH-SY5Y cells apoptosis in Alzheimer's Disease cellular model. METHODS: The optimal concentration and treating time of Abeta25-35 for Alzheimer's Disease cellular model as well as those of WEAG were measured by flow cytometer. In addition, the cell viability was measured by MTT test and the morphology of SH-SY5Y cells was observed by Hoechst 33258 staining. RESULTS: Treated by Abeta25-35 50 micromol/L 72 h later, SH-SY5Y cells turned rounder, aggregated and were positively stained with fluorochrome Hoechst 33258. Cells displayed a typical sub-diploid peak in flow cytometry, and the percentage of apoptosis reaches (37.30 +/- 0.69)% (P < 0.05 as compared with the control group) (1.56 +/- 0.80)%. When incubated with Abeta 50 micromol/L and different doses (0.5, 1, 5 mg/ml) of WEAG for 72h, the characteristics of apoptosis as measured by FCM dose-dependently declined to (16.71 +/- 1.08)%, (10.52 +/- 2.11)% and (3.39 +/- 1.65)%, respectively (P < 0.05 as compared with the model group). CONCLUSION: Water extracts of American Ginseng have markedly neuroprotective effects on SH-SY5Y cells apoptosis induced by Abeta25-35.