Insights into the binding specificity and catalytic mechanism ofN-acetylhexosamine 1-phosphate kinases through multiple reaction complexes

Utilization of N-acetylhexosamine in bifidobacteria requires the specific lacto-N-biose/galacto-N-biose pathway, a pathway differing from the Leloir pathway while establishing symbiosis between humans and bifidobacteria. The gene lnpB in the pathway encodes a novel hexosamine kinase NahK, which catalyzes the formation of N-acetylhexosamine 1-phosphate (GlcNAc-1P/GalNAc-1P). In this report, seven three-dimensional structures of NahK in complex with GlcNAc, GalNAc, GlcNAc-1P, GlcNAc/AMPPNP and GlcNAc-1P/ADP from both Bifidobacterium longum (JCM1217) and B. infantis (ATCC15697) were solved at resolutions of 1.5-2.2 Å. NahK is a monomer in solution, and its polypeptide folds in a crescent-like architecture subdivided into two domains by a deep cleft. The NahK structures presented here represent the first multiple reaction complexes of the enzyme. This structural information reveals the molecular basis for the recognition of the given substrates and products, GlcNAc/GalNAc, GlcNAc-1P/GalNAc-1P, ATP/ADP and Mg(2+), and provides insights into the catalytic mechanism, enabling NahK and mutants thereof to form a choice of biocatalysts for enzymatic and chemoenzymatic synthesis of carbohydrates

Patient-controlled epidural Levobupicvacaine with or without Fentanyl for post-cesarean section pain relief

Purpose. The purpose of this study was to compare the analgesic properties of levobupivacaine with or without fentanyl for patient-controlled epidural analgesia after Cesarean section in a randomized, double-blinded study. Methods. We enrolled American Society of Anesthesiologists class I/II, full-term pregnant women at National Taiwan University Hospital who received patient-controlled epidural analgesia after Cesarean section between 2009 and 2010. Eighty women were randomly assigned into two groups. In group A, the 40 subjects received drug solutions made of 0.6 mg/ml levobupivacaine plus 2 mcg/ml fentanyl, and in group B the 40 subjects received 1 mg/ml levobupivacaine. Maintenance was self-administered boluses and a continuous background infusion. Results. There were no significant differences in the resting and dynamic pain scales and total volume of drug used between the two groups. Patient satisfaction was good in both groups. Conclusion. Our study showed that pure epidural levobupivacaine can provide comparative analgesic properties to the levobupivacaine-fentanyl combination after Cesarean section. Pure levobupivacaine may serve as an alternative pain control regimen to avoid opioid-related adverse events in parturients

Study on the continuous phase evolution and physical properties of gas-atomized high-entropy alloy powders

In this study, AlCoCrFeNi high entropy alloy (HEA) powders were fabricated by gas atomization process, and the effects of annealing heat treatment on phase evolution and mechanical properties were investigated. The as-atomized powders have pure BCC phase with a spherical shape and equal composition distribution, and then the FCC and sigma phase sequentially generated after annealing. The mechanical property such as hardness was evidently enhanced, which was caused by precipitation hardening effect. After the raw powders were annealed at 600 °C, the FCC (Al-Ni) phase began to precipitate, the its phase intensity raised with the annealing temperature. Then, the sigma phase (Fe-Cr) formed as the annealing temperature reached 800 °C. Both mechanical properties and lattice constant were influenced by heating effect. According to the results, the lattice became loose with the increasing temperature. In summary, the mechanical properties and phase constitutions of gas-atomized AlCoCrFeNi HEA powders can be adjusted via annealing process, resulting in precipitation hardening effect

Role of Bone Morphogenetic Proteins-7 (BMP-7) in the Renal Improvement Effect of DangGui (Angelica sinensis) in Type-1 Diabetic Rats

Hyperglycemia induced reactive oxygen species (ROS) generation is believed as major factors leading to diabetic nephropathy (DN). DangGui (Angelica sinensis) is mentioned to show renal protective effect in combination with other herbs. Bone morphogenetic proteins-7 (BMP-7) is produced merit in protection of DN. The role of BMP-7 in DangGui-induced renal improvement is not clear. The present study investigated the effects of DangGui on renal functions, BMP-7 expression and the levels of ROS in streptozotocin (STZ)-induced diabetic rats and high glucose-exposed rat mesangial cells (RMCs). After 1- or 4-week treatment, DangGui improved renal functions and increased renal BMP-7 expression in diabetic rats. The BMP-7 expression in RMCs was reduced by high glucose treatment and this could be reversed by DangGui. Moreover, RMCs exposed to high glucose were expired by BMP-7 RNAi transfection but those cells remained alive by scramble transfection. Thus, we employed regular RMCs to knock down BMP-7 with RNAi and we found that DangGui increased BMP-7 expression in these RMCs. Direct activation of BMP-7 expression by DangGui could be considered. The results of DPPH assay, DHE stain and lucigenin assay indicated that DangGui could inhibit high glucose-induced ROS in RMCs. These results suggest that DangGui has an ability to improve renal functions in STZ-diabetic rats through increasing endogenous BMP-7 expression and decreasing oxidative stress in kidney. The present study suggest that DangGui could be applied to improve renal functions in diabetic disorders

Use of Chinese Herbal Medicine Was Related to Lower Risk of Osteoporotic Fracture in Sarcopenia Patients: Evidence from Population-Based Health Claims

Introduction: With population aging, sarcopenia and its accompanying risk of osteoporotic fracture has drawn increased attention. Nowadays, while Chinese herbal medicine (CHM) is often used as complementary therapy for many medical conditions, its effect against likelihood of osteoporotic fracture among sarcopenia subjects was not fully elucidated yet. We therefore conducted a population-level study to compare osteoporotic fracture risk for sarcopenia persons with or without CHM use. Methods: Using the patient record from a nationwide insurance database, we recruited persons with newly diagnosed sarcopenia and simultaneously free of osteoporotic fracture between 2000 and 2010. Propensity score matching was then applied to randomly select sets of CHM users and non-CHM users. All of them were tracked until end of 2013 to measure the incidence and adjusted hazard ratios (HRs) for new new-onset fracture in multivariable Cox proportional hazards model. Results: Compared to non-CHM users, the CHM users indeed had a lower incidence of osteoporotic fracture (121.22 vs 156.61 per 1000 person-years). Use of CHM correlated significantly with a lower fracture likelihood after adjusting for potential covariates, and those receiving CHM treatment for more than two years experienced a remarkably lower risk by 73%. Uses of several herbal formulae were correlated to reduced risk of osteoporotic fracture, such as Caulis Spatholobi, Xuduan, Duzhong, Danshen, Shu-Jing-Huo-Xue- Tang, Du-Huo-Ji-Sheng-Tang, Shao-Yao-Gan-Cao-Tang, and Shen-Tong-Zhu-Yu -Tang. Conclusion: Our study depicted that cumulative CHM exposure was inversely associated with osteoporotic fracture risk in a duration-dependent manner, implying that CHM treatment may be embraced as routine care in preventing incident osteoporotic fracture

Effects of a Chinese Herbal Medicine, Guan-Jen-Huang (Aeginetia indica Linn.), on Renal Cancer Cell Growth and Metastasis

Aeginetia indica Linn. (Guan-Jen-Huang, GJH), a traditional Chinese herb, has the potential to be an immunomodulatory agent. The purpose of this study was to explore the effect of GJH in the treatment of renal cancer. Concentration-effect curves for the influence of GJH on cellular proliferation showed a biphasic shape. Besides, GJH had a synergistic effect on cytotoxicity when combined with 5-fluorouracil (5-FU)which may be due to the alternation of the chemotherapeutic agent resistance-related genes and due to the synergistic effects on apoptosis. In addition, treatment with GJH extract markedly reduced 786-O cell adherence to human umbilical vein endothelial cells (HUVECs) and decreased 786-O cell migration and invasion. In a xenograft animal model, GJH extract had an inhibitory effect on tumor cell-induced metastasis. Moreover, western blot analysis showed that the expression of intercellular adhesion molecule-1 (ICAM-1) in 786-O cells was significantly decreased by treatment with GJH extract through inactivation of nuclear factor-κB (NF–κB). These results suggest that GJH extract has a synergistic effect on apoptosis induced by chemotherapeutic agents and an inhibitory effect on cell adhesion, migration, and invasion, providing evidence for the use of water-based extracts of GJH as novel alternative therapeutic agents in the treatment of human renal cancer