Causal relationship between Interleukin-27 expression levels and osteoporosis: a bidirectional mendelian randomization study.

BACKGROUND: This study aimed to evaluate the causal relationship between Interleukin-27 (IL-27) and osteoporosis by bidirectional Mendelian randomization (MR) analysis. METHODS: Firstly, the genome-wide association study summary data of osteoporosis (finn-b-M13_OSTEOPOROSIS) and IL-27 levels (ebi-a-GCST90012017) were picked out from the Integrative Epidemiology Unit (IEU) OpenGWAS database. After filtrating instrumental variables (IVs), the bidirectional MR analysis between IL-27 levels and osteoporosis was performed by MR-Egger, Weighted median, Simple mode, Weighted mode, and Inverse variance weighted (IVW). Subsequently, the sensitivity analysis was adopted to evaluate the reliability of the MR results via the Heterogeneity, Horizontal pleiotropy test and Leave-One-Out (LOO) analysis. Finally, the enrichment analysis of genes corresponding to SNPs related to IL-27 levels derived from eQTLGen database was executed to explore in depth the biological function and regulatory mechanism of these genes on osteoporosis occurrence. RESULTS: The bidirectional MR results based on IVW method revealed that IL-27 level as a risk factor was causally related to osteoporosis (P = 0.004, odds ratio (OR) = 1.123, 95% confidence interval (CI) = 1.037-1.217), whereas osteoporosis was not in significant connection with IL-27 levels (P > 0.05). In regard to the sensitivity analysis for forward MR results, there was no heterogeneity and horizontal pleiotropy, and no SNPs relevant to IL-27 levels existed severe bias, suggesting the reliability of forward MR analysis. Furthermore, a total of 74 genes corresponding to 26 SNPs of IL-27 levels were obtained and were mainly involved in immune and inflammatory pathways including MyD88-dependent toll-like receptor signaling pathway, Toll-like receptor signaling pathway, cytosolic DNA-sensing pathway and so forth. CONCLUSIONS: This study supported that IL-27 level as a risk factor was causally connected with osteoporosis and might regulate the disease occurrence and progression by means of immune and inflammatory mechanisms, which could provide important reference and evidence for further exploring the role of IL-27 in the development of osteoporosis.

An Effective Osteogenesis Porous CaP/Collagen Interface Compatible with Various Substrates Fabricated by Controlled Mineralization in a Delicately Adjustable Organic Matrix.

Increasing bone formation on the surfaces of implants such as screws, plates, or shims holds great significance for clinical medicine. However, osteogenesis implant coatings that mimic natural bone in terms of both their components and structural features are still lacking. Here we report the biomimetic interface of calcium phosphate (CaP) in a collagen matrix fabricated by controlled mineralization that presents biomimetic porous features. The porous CaP/collagen interface, with a thickness of about 1 µm, significantly enhances osteogenesis, as verified at both the gene and protein levels as well as by in vivo experiments. Taking advantage of the generality of the method, the biomimetic interface was prepared on a variety of substrates, including conductive substrates, 3D metal meshes, plastic or elastic substrates, and even on filter papers. The adjustability and generality of the method have enabled new characterization tests to be developed during experiments on cells and thus should greatly facilitate clinical medicine and tissue engineering.

[Non-leaching, broad-spectrum antibacterial poly (ε-caprolactone)/gelatin-QAS nanofiberous membranes for wound dressing].

5-20 wt% trimethoxysilylpropyl octadecyldimethyl ammonium chloride (QAS) was used to modify Poly (ε-caprolactone) (PCL)-gelatin hybrid to fabricate non-leaching antibacterial nanofiber membranes (PG-Q) by electrospinning. The results from scanning electron microscopy (SEM) and transmission electron microscopy (TEM) indicated that the QAS leaded to phase separation between the QAS and PCL. Hydrophilic test demonstrated that the PG-Q nanofiber membranes had hydrophobic surface, which was help for peeling off the dressing from the wound. Additionally, the physical and chemical cross-linking between the QAS/PCL and QAS/gelatin were confirmed by Fourier transform infrared (FTIR), which were good for long lasting antibacterial effect. The PG-Q membranes also showed excellent cell-biocompatibility. Furthermore, compared with pure PCL nanofiber membrane, the PG-Q nanofiber membranes, especially PG-Q15 (QAS: 15 wt%) and PG-Q20 (QAS: 20 wt%), showed a considerable increase in the bacteriostatic rate of S. aureus and P. aeruginosa (more than 99% after 12 h). Therefore, electrospinning non-leaching antibacterial nanofiber membranes could be an optimal choice for antibacterial wound dressing.

Influence of age-related learning and memory capacity of mice: different effects of a high and low caloric diet.

BACKGROUND: Recent studies indicate that consumption of the different calorie diet may be an important way to accelerate or slow the neurodegenerative disorder related to age. Long-term consumption of a high-calorie diet affects the brain and increase the risk of neurodegenerative disorders. And consumption of a low-calorie diet (caloric restriction, CR) could delay aging, and protect the central nervous system from neurodegenerative disorders. The underlying mechanisms have not yet been clearly defined. METHOD: Thirty 6-week-old C57/BL6 mice were randomly assigned to a NC group (fed standard diet, n = 10), a CR group (fed a low-calorie diet, n = 10) or a HC group (fed a high-calorie diet, n = 10) for 10 months. Body weight was measured monthly. Learning and memory capacity were determined by Morris water maze. Pathological changes of the hippocampus cells were detected with HE and Nissl staining. The expression of GFAP was determined by immunofluorescence and western blot. The expression of mTOR, S6K and LC3B in the hippocampus was determined by immunofluorescence. RESULTS: After feeding for 10 months, compared with mice in the NC group, mean body weight was significantly higher in the HC group and significantly lower in the CR group. The result of Morris water maze showed that compared with mice in the NC group, the learning and memory capacity was significantly increased in the CR group, and significantly decreased in the HC group. HE and Nissl staining of the hippocampus showed cells damaged obviously in the HC group. In the hippocampus, the expression of GFAP, mTOR and S6K was increased in the HC group, and decreased in the CR group. The expression of LC3B was decreased in the HC group, and increased in the CR group. CONCLUSIONS: Long-term consumption of a high-calorie diet could inhibit autophagy function, and facilitate neuronal loss in the hippocampus, which in turn aggravate age-related cognition impairment. And consumption of a low-calorie diet (caloric restriction, CR) could enhance the degree of autophagy, protect neurons effectively against aging and damage, and keep learning and memory capacity better.

The ß-amyloid precursor protein analog P165 improves impaired insulin signal transduction in type 2 diabetic rats.

This study was performed to understand whether P165 improves learning and memory by restoring insulin action using a diabetes mellitus (DM) rat model. A total of 34 male Sprague-Dawley rats were randomly divided into four groups: control group (n = 8), DM group (n = 8), DM group treated with a low dose of P165 (n = 9), and DM group treated with a high dose of P165 (n = 9). After 8 weeks of treatment, the animals were killed and the expression of insulin signaling-related proteins was examined in the hippocampus by Western blot and immunohistochemical staining. Administration of P165 in diabetic rats did not induce a significant effect on the fasting blood glucose level. The expression of IR, IRS-1, AKT, p-CREB, and Bcl-2 proteins was significantly enhanced in the hippocampus in diabetic rats. Treatment of diabetic rats with P165 at both low and high doses significantly attenuated the expression levels of these proteins. Moreover, immunohistochemistry staining showed that IR, IRS-1, AKT, p-CREB, and Bcl-2 were abundantly expressed in the CA1 region of the hippocampus. The number of cells positively stained for the above proteins was significantly higher in diabetic tissues compared to control tissues, whereas P165 treatments induced a significant reduction in the expression of these proteins. The expression of IR, IRS-1, AKT, p-CREB, and Bcl-2 was enhanced in DM rats, and administration of P165 normalized the expression of these molecules, suggesting that P165 can improve impaired insulin signal transduction.

Caloric restriction can improve learning ability in C57/BL mice via regulation of the insulin-PI3K/Akt signaling pathway.

To identify the molecular mechanism underlying improved spatial learning ability of C57/BL mice on a caloric restricted (CR) diet. Seven-week-old male C57/BL mice were randomly divided into three groups: normal control group (NC group, n = 10), high energy group (n = 10), and low energy group (CR group, n = 10). Body mass and levels of blood glucose were measured every 2 weeks over the course of 30 weeks. After 30 weeks, metabolic parameters, serum total cholesterol, and insulin-like growth factor 1 (IGF-1) were measured, and learning and memory ability of animals were tested using the Morris water maze. The expression of insulin signaling pathway-related proteins in the brain tissues also were tested for molecular mechanism. When compared with the NC group, body weight, and levels of serum glucose decreased in the CR group and increased in the high energy group at all time points tested. Average escape latency and swimming distance were lower in the CR group as compared to the control group after 30 weeks. The serum cholesterol level of the high energy group was significantly higher than that of the control group. The expressions of IGF-1, IR, IRS-1, PI3K, Akt/PKB, and p-CREB protein in the CR group were significantly lower and the expressions of PI3K and Akt/PKB protein in the high energy group were significantly lower than those of the control group at post 30 weeks treatment. Our findings demonstrate that the low energy diet may improve hippocampus-dependent spatial learning ability in C57/BL mice, possibly through a regulatory mechanism of the insulin-PI3K/Akt signaling pathway.

Effect of Basalt Fiber Content and Length on the Strength and Crack Development of Polyvinyl Alcohol/Basalt Hybrid Fiber-Reinforced Cement Soil.

Polyvinyl alcohol (PVA) fiber is widely used in geotechnical engineering because of its excellent physical and mechanical properties; however, PVA fibers are prone to aging, while basalt fiber has a natural anti-aging ability, which can be added to cement material to effectively eliminate the effects of aging on PVA fiber. Previous experiments identified that the optimum content of PVA fiber is 0.5% (mass fraction, the same below). Based on this, we continued to add basalt fibers of different lengths (3 mm, 6 mm, 9 mm, 12 mm, 18 mm, 30 mm) and different contents (0%, 0.25%, 0.5%, 0.75%, 1%) to study the effect of both length and content of basalt fibers on the strength of cement soil specimens. It was concluded that adding 0.5 % of 9 mm basalt fiber results in the greatest increase in unconfined compressive strength (UCS). The UCS reached 12.59 MPa, which was 71% higher than specimens without fiber, and a regression analysis was carried out to obtain the relationship among them. The ratio of cement soil in the highest UCS and the relationship among the UCS, the length, and the content of basalt fiber can be used as a reference for practical projects. In addition, digital image correlation (DIC) technology was used to analyze the surface cracks and horizontal strain field when the peak strain was reached at each content and length of the basalt fiber. Finally, the curing mechanism for hybrid fiber cement soil was analyzed by combining the results of the UCS test, DIC test, and SEM test.

Study on Nanoporous Graphene-Based Hybrid Architecture for Surface Bonding.

Graphene-copper nanolayered composites have received research interest as promising packaging materials in developing next-generation electronic and optoelectronic devices. The weak van der Waal (vdW) contact between graphene and metal matrix significantly reduces the mechanical performance of such composites. The current study describes a new Cu-nanoporous graphene-Cu based bonding method with a low bonding temperature and good dependability. The deposition of copper atoms onto nanoporous graphene can help to generate nanoislands on the graphene surface, facilitating atomic diffusion bonding to bulk copper bonding surfaces at low temperatures, according to our extensive molecular dynamics (MD) simulations on the bonding process and pull-out verification using the canonical ensemble (NVT). Furthermore, the interfacial mechanical characteristics of graphene/Cu nanocomposites can be greatly improved by the resistance of nanostructure in nanoporous graphene. These findings are useful in designing advanced metallic surface bonding processes and graphene-based composites with tenable performance.

Electrospun artificial periosteum loaded with DFO contributes to osteogenesis via the TGF-ß1/Smad2 pathway.

Deferoxamine (DFO), an iron chelator regarded as a hypoxic analogue, has been reported to be involved in angiogenesis and osteogenic differentiation. In this study, DFO was loaded into nanospheres, Then, DFO-loaded NPs and free DFO were co-encapsulated in nanofibers through coaxial electrospinning and its effects on cell viability, migration, and osteogenic differentiation, and the potential mechanisms were investigated. The results suggested that DFO maintained cell viability and promoted the migration of human mesenchymal stem cells (hMSCs) and MC3T3-E1 cells. ALP activity, calcium deposition, and expression of osteogenesis-related markers, including collagen, osteocalcin, and osteopontin, were all increased with DFO. Moreover, hypoxia-inducible factor-1α, transforming growth factor-ß, and Smad2 were upregulated with DFO, which indicated activation of the TGF-ß1/Smad2 signalling pathway. This may contribute to osteogenic differentiation of cells.

Smart Titanium Coating Composed of Antibiotic Conjugated Peptides as an Infection-Responsive Antibacterial Agent.

Antibacterial coating is rapidly emerging as a pivotal strategy for mitigating spread of bacterial pathogens. However, many challenges still need to be overcome in order to develop a smart coating that can achieve on-demand antibacterial effects. In this study, a Staphylococcus aureus (S. aureus) sensitive peptide sequence is designed, and an antibiotic is then conjugated with this tailor-made peptide. The antibiotic-peptide conjugate is then linked to the surface of a titanium implant, where the peptide can be recognized and cleaved by an enzyme secreted by S. aureus. This allows for the release of antibiotics in the presence of S. aureus, thus achieving delivery of an antibacterial specifically when an infection occurs.

Biofunctionalization of electrospun fiber membranes by LbL-collagen/chondroitin sulfate nanocoating followed by mineralization for bone regeneration.

It is of great significance to develop osteoinductive artificial scaffold for bone repair and regeneration. We constructed a biomimetic apatite interface on electrospun polycaprolactone fibers by combining layer-by-layer (LbL) nanocoating with mineralization to fabricate an osteoinductive artificial scaffold. After polydopamine modification, cationic type-І collagen and anionic chondroitin sulfate were sequentially adsorbed on the fiber surface. The fibers coated with the multilayer components served as the precursor matrix to induce apatite deposition. By adjusting the number of the layers and duration of mineralization, the nanoscale morphology of composite fibers was optimized. When ten bilayers of the collagen and chondroitin sulfate were deposited onto the fibers followed by one day-mineralization, the obtained polycaprolactone-apatite composite scaffolds significantly promoted the adhesion, proliferation, and osteogenic differentiation of MC3T3-E1 cells. In a subcutaneous implantation in mice, this composite fiber membrane enhanced in vivo ectopic osteogenesis. Our nano-architectural scaffolds were able to mimic the composition and structure of the bone matrix to a certain extent, holding great potential for bone repair and regeneration.

Effective delivery of mitomycin-C and meloxicam by double-layer electrospun membranes for the prevention of epidural adhesions.

Epidural adhesion between the spinal dura and the surrounding fibrous tissue often occurs post-laminectomy, resulting in clinical symptoms such as nerve compression and severe pain. In this study, we report a drug-loaded double-layered electrospun nanofiber membrane to prevent the occurrence of epidural adhesion. The nanofibers in both layers are made of a mixture of polycaprolactone (PCL) and chitosan (CS) but at different weight ratios. The bottom layer contacting to the spinal dura is loaded with meloxicam (MX) to prevent inflammation. The top layer that contacts to the fibrous tissue is doped with mitomycin-C (MMC) to inhibit the synthesis of DNA and collagen. The two types of drugs are released from the double-layered membrane within about 12 days. Meanwhile, the membrane can inhibit fibroblasts proliferation in vitro while show no cytotoxicity. In a rabbit laminectomy model, the double-layered membrane can effectively prevent the epidural adhesion formation based on the adhesion scores, histological and biochemical evaluations. The combination release of MX and MMC can signally reduce the inflammation reaction and collagen I/III expression relative to the case with the membranes loaded with only either one type of the drugs. This approach offers new progresses in constructing dual drug delivery system and provides innovative barrier strategy in inhibiting epidural adhesion post-laminectomy.

Infection-responsive electrospun nanofiber mat for antibacterial guided tissue regeneration membrane.

The release of anti-infection drugs in a targeted and efficient manner in response to the attack time and degree of severity of infection is a requirement of new generation implants. Herein, we design an infection-responsive guided tissue regeneration (GTR)/guided bone regeneration (GBR) membrane based on electrospun nanofibers. Polycaprolactone (PCL) nanofiber mats are coated with polydopamine to endow hydroxyl groups on the surface and then functionalized with siloxane to introduce amino groups. Metronidazole (MNA), an antibiotic drug, is esterified and then grafted onto the surface of the modified PCL nanofiber mats via ester linkages. The ester bonds can be selectively hydrolyzed by cholesterol esterase (CE), an enzyme secreted by macrophagocytes accumulated at the site of infection, whose concentration is positively related to the severity of the infection. The drug can be triggered to release from the nanofiber membranes in responsive to the CE. With the increase of the CE concentration, a higher amount of MNA is released from the nanofiber mat, resulting in the enhancement of the antibacterial capability of the MNA-grafted nanofiber mat. The nanofiber mat has good cytocompatibility. This CE-responsive drug delivery system based on the electrospun nanofiber mat is promising as an optimal choice for antibacterial GTR/GBR membrane.

Icariin-loaded electrospun PCL/gelatin sub-microfiber mat for preventing epidural adhesions after laminectomy.

BACKGROUND: Epidural adhesion is one of the major reasons attributed to failed back surgery syndrome after a successful laminectomy, and results in serious clinical complications which require management from physicians. Therefore, there is an urgent demand within the field to develop biodegradable anti-adhesion membranes for the prevention of post-operative adhesion. METHODS: In this study, icariin (ICA) was initially loaded into polycaprolactone (PCL)/gelatin fibers via electrospinning to fabricate nanofibrous membranes. The effects of the ICA content (0.5wt%, 2wt% and 5wt%) and the bioactivity of ICA in the nanofibrous membranes were investigated in vitro and in vivo. RESULTS: The nanofibrous membranes showed suitable pore size and good properties that were unaffected by ICA concentration. Moreover, the ICA-loaded membranes exhibited an originally rapid and subsequently gradual sustained ICA release profile that could significantly prevent fibroblast adhesion and proliferation. In vivo studies with rabbit laminectomy models demonstrated that the ICA-loaded membranes effectively reduced epidural adhesion by gross observation, histology, and biochemical evaluation. The anti-adhesion mechanism of ICA was found to be via suppression of the TGF-ß/Smad signaling proteins and down regulation of collage I/III and a-SMA expression for the first time. CONCLUSION: We believe that these ICA-loaded PCL/gelatin electrospun membranes provide a novel and promising strategy to resist adhesion formation following laminectomy in a clinical application.

Resveratrol prevents high-calorie diet-induced learning and memory dysfunction in juvenile C57BL/6J mice.

OBJECTIVE: Because resveratrol (RSV) has been shown to improve learning and memory, so we investigated the potential benefit of RSV on learning and memory deficits in juvenile mice fed with a HC diet and explored the molecular mechanisms underlying this process. METHODS: Six-week-old C57BL/6J mice were divided into three different diet groups: control, HC diet, and HC + RSV diet. Serum insulin and insulin-like growth factor 1 (IGF-1) levels were measured using enzyme-linked immunosorbent assays. Protein expression was examined by immunohistochemistry and western blotting. RESULTS: Administration of RSV daily (30 mg/kg) prevented the HC diet-induced increase in juvenile animal body weight but did not improve any other physiological conditions, including fasting blood glucose and serum cholesterol, triglyceride, insulin, and IGF-1 levels. However, RSV did prevent learning and memory deficits in the HC group. Peroxisome proliferator-activated receptor gamma (PPARγ) was downregulated in the CA1 region of the hippocampus in both the HC and HC + RSV groups, but the reduction was significantly greater in the HC + RSV group (P < .01 compared with the HC group). Moreover, although the HC diet reduced the number of p16-positive neurons, the HC + RSV diet significantly upregulated p16 expression in the CA1 region of the hippocampus (P < .01 compared with the HC group). CONCLUSIONS: RSV protected against learning and memory impairments in juvenile animals fed with a HC diet, possibly via upregulation of p16 or downregulation of PPARγ in the hippocampal CA1 region.

Long-term caloric restriction in mice may prevent age-related learning impairment via suppression of apoptosis.

Caloric restriction (CR) is the most reliable intervention to extend lifespan and prevent age-related disorders in various species from yeast to rodents. However, the underlying mechanisms have not yet been clearly defined. Therefore, we aimed to identify the underlying mechanisms of long-term CR on age-related learning impairment in C57/BL mice. Thirty six-week-old male C57/BL mice were randomly divided into three groups: normal control group (NC group, n=10), high energy group (HE group, n=10), and CR group (n=10). After 10 months, the Morris water maze test was performed to monitor learning abilities. Western blotting, immunohistochemistry and real-time polymerase chain reaction were used to monitor changes in protein and mRNA levels associated with apoptosis-related proteins in the hippocampus. The average escape latency was lower in the CR group compared with the NC group, and the average time taken to first cross the platform in the CR group was significantly shorter than the HE group. Both Bcl-2 protein and mRNA expression levels in the CR group were significantly higher than those of the NC group and HE group. The expression of Bax, Caspase-3 and PARP protein in the CR group was significantly lower than the NC group. Our findings demonstrate that long-term CR may prevent age-related learning impairments via suppressing apoptosis in mice.

Effect of caloric restriction on the SIRT1/mTOR signaling pathways in senile mice.

AIMS: To determine the effects and underlying molecular mechanisms of caloric restriction (CR) in C57BL/6 mice. METHODS: Thirty-six 6-week-old male C57BL/6 mice were assigned to a normal control group (NC, n=12), a high energy group (HE, n=12), and a CR group (n=12), and received a normal diet, a high-calorie diet, or a calorie-restricted diet, respectively, for 44 weeks. Body weight and serum glucose concentration were regularly recorded, and animals were sacrificed and hippocampus tissues were collected for immunohistochemistry (n=6 per group), western blotting (n=3 per group) and real-time polymerase chain reaction (n=3 per group) analysis at the end of the 44-week experimental period. Immunohistochemistry, western blotting and real-time polymerase chain reaction were used to detect changes in hippocampal proteins may be involved in the SIRT1/mTOR pathways. RESULTS: Body weight and serum glucose over the 44 weeks in animals from the CR group were lower than those of HE group. The number of SIRT1-immunoreactive cells in the CR group was significantly higher than in the NC and HE groups, and SIRT1 mRNA expression in the CR group was significantly higher than that in the HE group, but there was no difference in SIRT1 protein expression among the three groups. mTOR and S6K1 protein activation and mTOR and S6K1 mRNA were significantly lower in the CR group than in the NC group. CONCLUSIONS: Our findings suggest that a CR diet could lead to activation of SIRT1 and suppression of mTOR and S6K1 activation in C57BL/6 mice. We have shown that the SIRT1/mTOR signaling pathways may be involved in the neuroprotective effect of CR.

Effects of Caloric Intake on Learning and Memory Function in Juvenile C57BL/6J Mice.

Dietary composition may influence neuronal function as well as processes underlying synaptic plasticity. In this study, we aimed to determine the effect of high and low caloric diets on a mouse model of learning and memory and to explore mechanisms underlying this process. Mice were divided into three different dietary groups: normal control (n = 12), high-caloric (HC) diet (n = 12), and low-caloric (LC) diet (n = 12). After 6 months, mice were evaluated on the Morris water maze to assess spatial memory ability. We found that HC diet impaired learning and memory function relative to both control and LC diet. The levels of SIRT1 as well as its downstream effectors p53, p16, and peroxisome proliferator-activated receptor γ (PPARγ) were decreased in brain tissues obtained from HC mice. LC upregulated SIRT1 but downregulated p53, p16, and PPARγ. The expressions of PI3K and Akt were not altered after HC or LC diet treatment, but both LC and HC elevated the levels of phosphorylated-cAMP response element-binding protein (p-CREB) and IGF-1 in hippocampal CA1 region. Therefore, HC diet-induced dysfunction in learning and memory may be prevented by caloric restriction via regulation of the SIRT1-p53 or IGF-1 signaling pathways and phosphorylation of CREB.

The level of Alzheimer-associated neuronal thread protein in urine may be an important biomarker of mild cognitive impairment.

Increased levels of Alzheimer-associated neuronal thread protein (AD7c-NTP) are often detected in urine in the early course of Alzheimer's disease (AD), which makes it a promising biomarker for AD. However, whether the concentration of urinary AD7c-NTP is increased in patients with mild cognitive impairment (MCI) remains unclear. The aim of this study was to explore the value of urinary AD7c-NTP to assist in the diagnosis of cognitive impairment by comparing differences in urinary AD7c-NTP among normal controls, MCI patients and AD patients. One hundred and seventy patients from the Xuan wu Hospital, Capital Medical University were divided into three groups according to their clinical diagnosis: an AD group (n=45), an MCI group (n=60) and a normal group (n=65). The Mini Mental State Examination and the Montreal Cognitive Assessment scale were used to screen for the diagnosis of AD and MCI, and patients met the diagnostic criteria of the National Institute of Neurological Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. The level of urinary AD7c-NTP was determined using the enzyme-linked immunosorbent assay method. The urinary levels of AD7c-NTP in the AD group (median 2.14 [range 0.49-6.39] ng/ml) and the MCI group (median 1.57 [range 0.4-4.15] ng/ml) were significantly higher than those of the normal group (median 0.53 [range 0.04-2.07] ng/ml). To our knowledge our study is the first to show that the level of urinary AD7c-NTP in MCI patients is higher than in healthy people, which suggests that the level of urinary AD7c-NTP may be an important biomarker for early diagnosis of MCI.

Rosiglitazone improves learning and memory ability in rats with type 2 diabetes through the insulin signaling pathway.

Diabetes mellitus (DM) is associated with moderate cognitive deficits and neurophysiologic and structural changes in the brain, a condition that is referred to as diabetic encephalopathy. This study was performed to investigate the effect of rosiglitazone (RSG) on learning and memory in rats with DM and elucidate possible mechanisms underlying this condition. Thirty-two male Sprague-Dawley rats were randomly divided into 4 groups: control (C, n = 8), DM (n = 8), RSG-administered control (C + RSG, n = 8) and RSG-administered DM groups (DM + RSG, n = 8). At 8 weeks after drug administration, Morris water maze was used to perform a training and probe trial to detect spatial learning and memory abilities. Western blot and immunohistochemistry were also used to detect changes in proteins involved in the insulin signal transduction pathway, such as the insulin receptor, insulin receptor substrate-1, protein kinase B, phosphorylated cAMP response element-binding protein and B-cell lymphoma 2, in the hippocampus of the rats. This study found that RSG could normalize the impaired insulin signal transduction in type 2 DM. The authors showed that RSG modulated the central insulin signaling axis.