In traditional Chinese Medicine (TCM), the licorice-yuanhua herbal pair is one of the most representative incompatible herbal pairs recorded in the “eighteen incompatible herbal pairs” theory. ...Previous studies of our research group have demonstrated several gut-related side-effects induced by the licorice-yuanhua herbal pair. In this study, we investigated whether and why this incompatible herbal pair could induce gut tissue damage. After licorice-yuanhua treatment, the duodenum, ileum, and colon and serum biomarkers of mice were examined by pathological staining, Western blot, and ELISA assays. The IEC-6 cells and LS174T cells were treated with licorice saponins, yuanhua flavonoids, and di-terpenes; iTRAQ-labeled proteomic technology was then used to explore their synergistic effects on mucosa cells, followed by verification of ZO-1 and MUC-2 protein expressions. The results showed that the licorice-yuanhua herbal pair induced ileum tissue injuries, including epithelial integrity loss, inflammation, and edema. These injuries were verified to be related to epithelial and mucous barrier weakening, such as downregulated ileum ZO-1 and MUC-2 protein expressions. Proteomic analysis also suggested that glycyrrhizic acid and genkwanin synergistically influence tight junction pathways in LS174T cells. Furthermore, licorice saponins, yuanhua flavonoids, and di-terpenes dose/structure-dependently downregulate ZO-1 and MUC-2 protein expressions in mucosa cells. Our study provides different insights into the incompatibility mechanisms and material basis of the licorice-yuanhua herbal pair, especially that besides toxic di-terpenes, licorice saponins and yuanhua flavonoids, which are commonly known to be non-toxic compounds, can also take part in the gut damage induced by the licorice-yuanhua herbal pair.
•A Stackelberg game between one manufacturer and one online retailer is built.•The comparison of dynamic and static pricing strategies is studied.•Supply chain efficiency is the highest when only the ...manufacturer prices statically.•It aggravates the double marginalization that both channel members price dynamically.•The retailer’s pricing modes do not affect the manufacturer who prices statically.
With the rapid development of e-commerce, dynamic pricing, as a powerful tool to enhance company profits, has been widely adopted by companies worldwide. However, there are little researches which focus on the effects of dynamic pricing on supply chain performance. Noting that compared with the traditional retailer, it is easier for online retailer to implement dynamic pricing strategy, we consider a Stackelberg game between one manufacturer and one online retailer where the manufacturer, as the leader, decides the advertising effort and the wholesale price, and the online retailer, as the follower, sets the retail price. Specifically, the manufacturer simultaneously faces with the online retailer and an exogenous traditional distribution channel where both the wholesale price and the retail price are fixed and exogenous. Solving this differential game, we can obtain the equilibrium strategies. The results show that if the manufacturer prices dynamically, the manufacturer itself will be better off; however, the double marginalization will be aggravated, which is adverse to supply chain efficiency. In addition, the supply chain efficiency is the lowest when both the manufacturer and the online retailer price statically, and, interestingly, it is the highest when only the online retailer prices dynamically. Moreover, if the manufacturer prices uniformly, the equilibrium strategies of the manufacturer are independent of the pricing mode of the online retailer, i.e., static or dynamic. Additionally, dynamic pricing to some extent restricts the advertising investment.
Yunvjian (YNJ), a traditional Chinese herbal formula first reported in Jing Yue Quan Shu, is commonly used in the clinical treatment of type 2 diabetes mellitus (T2DM). However, the mechanism by ...which YNJ affects T2DM remains unclear.
This study aimed to assess the therapeutic effects of YNJ on T2DM and explore the potential mechanism involved.
High-performance liquid chromatography (HPLC) was used to identify the chemical compounds of YNJ. The anti-T2DM effects of YNJ were observed in a high-fat diet/streptozotocin induced rat model. The type 2 diabetic rats were prepared as follows: rats were fed a high-fat diet for four weeks and then intraperitoneally injected with a low dose (30 mg/kg) of streptozotocin. YNJ and the positive control metformin were used in these experiments. Biochemical assays were implemented to determine the fasting blood glucose, glucose tolerance, insulin sensitivity, serum lipid levels, and oxidative stress index of the pancreas. Hematoxylin-eosin (H&E) staining was used to assess histopathological alterations in the pancreas. The mechanism by which YNJ affects T2DM was evaluated in INS-1 cells treated with glucose and high sodium palmitate. YNJ-supplemented serum was used in these experiments. Methyl thiazolyl tetrazolium assays, enzyme-linked immunosorbent assays, Nile red staining, flow cytometric analysis, and Western blotting were used to assess apoptosis, insulin secretion, lipid accumulation, reactive oxygen species production, and protein levels.
Five major compounds were identified in YNJ. In high-fat diet/streptozotocin-induced diabetic rats, YNJ-M notably decreased fasting blood glucose and lipid levels; ameliorated glucose tolerance, insulin sensitivity, and islet morphology; reduced Malondialdehyde levels; and restored superoxide dismutase activity in the pancreatic islets. Furthermore, the effect of YNJ-M was significantly greater than that of YNJ-L, and YNJ-H had little effect on diabetic rats. In vitro experiments revealed that YNJ-supplemented serum (10%, 15%, and 20%) dramatically suppressed apoptosis, mitigated intracellular lipid accumulation and reduced intracellular oxidative stress levels in a dose-dependent manner. Additionally, YNJ-supplemented serum increased the protein expression of Nuclear factor erythroid 2-related factor 2, Heme oxygenase-1, and superoxide dismutase 1 and inhibited the protein expression of Kelch-like ECH-associated protein 1.
YNJ ameliorates high-fat diet/streptozotocin induced experimental T2DM. The underlying mechanism involves reducing oxidative stress in pancreatic beta cells. The findings of this study provide scientific justification for the application of the traditional medicine YNJ in treating T2DM.
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•The anti-diabetes effect of Yunvjian is confirmed in diabetic rat.•A protective mechanism of Yunvjian on pancreatic islet beta cell is proposed.•The mechanism relies on decreasing intracellular oxidative pressure in beta cells.
•A novel hIAPP amyloidogenic inhibitor is developed.•The mechanism behind the targeting of α-helical oligomers by the inhibitor at the membrane surface is revealed.•The mechanisms of inhibition at ...the membrane surface and in bulk solution are different.
A variety of peptides and peptide derivatives have been constructed using the “β-sheet core segment” of amyloid proteins as inhibitors of amyloidogenic fibrillation. A novel all-d-amino-acid from hIAPP β-sheet core segment (hIAPP 22–27) is demonstrated to inhibit hIAPP fibril formation efficiently both at the phospholipid membrane and in bulk solution. The inhibitor terminates hIAPP aggregation to the α-helical oligomeric intermediates at the membrane surface, whereas it stops the aggregation at the stage of β-sheet oligomeric intermediates in bulk solution. This is the first evidence that the inhibition mechanism of the inhibitor at membrane surface is significantly different from that in bulk solution.
hIAPP and hIAPPbind by transmission electron microscopy (View interaction)
hIAPP and hIAPPbind by atomic force microscopy (View interaction)
hIAPP and hIAPPbind by fluorescence technology (View interaction)
hIAPP and hIAPPbind by dynamic light scattering (View interaction)
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•Deuterohemin-AlaHisLys (DhHP-3), a peroxidase mimetic, mitigates the symptoms of rats with non-insulin dependent diabetes mellitus.•DhHP-3 protects pancreatic β-cells and promotes ...cell proliferation.•DhHP-3 scavenges reactive oxygen species induced by hyperglycemia.•PI3-K/AKT signal pathway is involved in the action of deuterohemin-AlaHisLys.
Damage to pancreatic β-cells plays an important role in the development of type 2 diabetes, and oxidative stress is a likely contributor. In the present study, we investigated the effect of deuterohemin-AlaHisLys (DhHP-3), a microperoxidase-11 mimic, on rats with non-insulin dependent diabetes mellitus and examined the action mechanisms of DhHP-3. The induced hyperglycemia, glucose intolerance, and insulin resistance in diabetic rats were associated with increased oxidative stress and damage to pancreatic islets. DhHP-3 (3mg/kg) ameliorated hyperglycemia and insulin resistance, protected pancreas islet, decreased the content of malondialdehyde, and increased the activity of superoxide dismutase in plasma and pancreatic tissue by reducing ROS levels. Furthermore, DhHP-3 stimulated the proliferation of INS-1 cells and inhibited apoptosis by activating the phosphatidylinositol 3-kinase/protein kinase B (PI3-K/AKT) signaling pathway. Our results demonstrated for the first time that DhHP-3 decreased blood glucose level in rats with non-insulin dependent diabetes mellitus, scavenged reactive oxygen species, activated the PI3-K/AKT signaling pathway, and protected pancreatic β-cells against apoptosis.
Pseudolarix amabilis (Nelson) Rehd, is a monotypic genus plant belonging to the family Pinaceae. The root bark , known as “Tu-Jin-Pi” has been used for the treatment of skin diseases. During our ...activity screening, the water-soluble part of the 70% EtOH extract of P. amabilis bark showed excellent inhibitory bioactivities on PTP1B enzyme, leading to the phytochemical isolation of the root bark of P. amabilis. Three oleanane-type compounds (1-3) and seven phenolic compounds (4-10) were isolated, in which oleanolic acid 3-O-β-D-glucuronyl-6′-ethyl ester (1) was identified as a new saponin. The chemical structures of these compounds were elucidated by 1D/2D nuclear magnetic resonance and high resolution mass spectra. In addition, their pharmacological inhibitory bioactivities on PTP1B enzyme were evaluated, and the three oleanane-type compounds 1-3 exhibited inhibitory bioactivities with IC50 values of 1.90 ± 0.37, 19.15 ± 0.10 and 10.44 ± 0.59 μM, respectively.
As greater attention is paid to energy consumption and global warming, magnetic refrigeration （MR） technologies based on the magneto-caloric effect （MCE） have been developed. Systems based on MR are ...expected to be more compact, energy efficient, and environmentally safe compared with traditional vapor-cycle refrigeration technologies .
<正>As greater attention is paid to energy consumption and global warming,magnetic refrigeration(MR)technologies based on the magneto-caloric effect(MCE)have been developed.Systems based on MR ...are expected to be more compact,energy
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