Benefit finding in chronic kidney disease patients receiving hemodialysis: a cross-sectional study.

BACKGROUND AND OBJECTIVES: The psychological problems of hemodialysis (HD) patients are prominent, and benefit finding (BF) have been proven beneficial to physical and mental health, fewer researchers explored BF in HD patients. The aim of this study was to investigate the current status of BF in patients with chronic kidney disease and to analyze the factors influencing it in order to provide a reference for subsequent interventions. METHODS: A cross-sectional study was done on 246 HD patients by convenience sampling in the hemodialysis center of a 3 A hospital in Shanghai from March to September 2019. The measures include General Information Questionnaire, Benefit Finding Scale, Perceived Social Support Scale, General Self-efficacy Scale, and Simplified Coping Style scale. RESULTS: The median (interquartile range, IQR) score of BF was 66 (IQR = 19) and it was lower compared with other chronic diseases. Significant differences in BF scores were found between different age groups, HD duration categories, and understanding degrees of HD. Taking BF as the dependent variable, the results of multiple linear regression analysis showed that age, duration of HD, family support, other support, positive coping, and self-efficacy entered the regression equation to explain 43.8% of the total variation. Social support played an indirect effect in the relationship between positive coping and BF, accounting for 54.1% of the total effect. CONCLUSION: The BF of HD patients is worrisome and affected by many factors. Medical staff could pay attention to the positive psychology of HD patients, and construct individualized interventions according to the influencing factors to improve their BF level and achieve physical and mental health.

Gsα deficiency in adipose tissue improves glucose metabolism and insulin sensitivity without an effect on body weight.

Gsα, the G protein that transduces receptor-stimulated cAMP generation, mediates sympathetic nervous system stimulation of brown adipose tissue (BAT) thermogenesis and browning of white adipose tissue (WAT), which are both potential targets for treating obesity, as well as lipolysis. We generated a mouse line with Gsα deficiency in mature BAT and WAT adipocytes (Ad-GsKO). Ad-GsKO mice had impaired BAT function, absent browning of WAT, and reduced lipolysis, and were therefore cold-intolerant. Despite the presence of these abnormalities, Ad-GsKO mice maintained normal energy balance on both standard and high-fat diets, associated with decreases in both lipolysis and lipid synthesis. In addition, Ad-GsKO mice maintained at thermoneutrality on a standard diet also had normal energy balance. Ad-GsKO mice had improved insulin sensitivity and glucose metabolism, possibly secondary to the effects of reduced lipolysis and lower circulating fatty acid binding protein 4 levels. Gsα signaling in adipose tissues may therefore affect whole-body glucose metabolism in the absence of an effect on body weight.

Effect of balloon dilation eustachian tuboplasty combined with tympanic tube insertion in the treatment of chronic recurrent secretory otitis media.

PURPOSE: To investigate the long-term clinical effect of balloon dilation eustachian tuboplasty (BET) combined with tympanic tube insertion (TTI) in the treatment of chronic recurrent secretory otitis media (CRSOM). MATERIALS AND METHODS: A retrospective study of 30 cases of CRSOM treated with BET combined with TTI under general anesthesia between August 2014 and September 2016. Thirty cases of CRSOM treated with TTI in the same period were taken as the control group. All cases were followed over 24 months. The scores of eustachian tube (ET) function preoperation, 1 month, 6 months, 12 months, and 24 months postoperation were collected and analyzed, respectively. A satisfaction questionnaire was used to evaluate the therapy at 24-months postoperation. RESULTS: The symptoms were significantly improved and the ET score was obviously increased postsurgery in most cases treated with BET plus TTI compared with those treated with TTI alone. The highest ET score was obtained at 6 months post BET. Five (14%) cases (6 ears) of CRSOM recurred. The 24-month postoperation follow-up questionnaire showed that 84.6% of the patients were satisfied with the treatment, while ten cases (25%) in the TTI group recurred. CONCLUSION: BET combined with TTI surgery is an effective therapy for patients with CRSOM.

Immobilization of a rhodium catalyst using a diphosphine-functionalized ionic liquid in RTIL for the efficient and recyclable biphasic hydroformylation of 1-octene.

A highly efficient and stable Rh-P catalytic system in the RTIL of [PEmim]BF4 was developed for the biphasic hydroformylation of 1-octene by using the diphosphine-functionalized ionic liquid (FIL) of 2. While 2-Rh(acac)(CO)2 was immobilized in [PEmim]BF4 (solvent), a typical biphasic catalysis was fulfilled with advantages of facile separation and recycling ability - 9 runs without any loss of activity. It was found that not only the acquired π-acceptor character of 2, but also the synergetic role of the piperidyl group in [PEmim]BF4 as an N-containing donor, cooperatively contributed to the efficient hydroformylation due to the facilitated formation and stability of the Rh-H active species (ν 2045 cm(-1)). This was supported by the in situ high-pressure FT-IR spectral analysis.

Protective effect of pranlukast on Aß1₋42-induced cognitive deficits associated with downregulation of cysteinyl leukotriene receptor 1.

Deposition of extracellular amyloid-ß (Aß) peptide is one of the pathological hallmarks of Alzheimer's disease (AD). Accumulation of Aß is thought to associate with cognition deficits, neuroinflammation and apoptosis observed in AD. However, effective neuroprotective approaches against Aß neurotoxicity are unavailable. In the present study, we analysed the effects of pranlukast, a selective cysteinyl leukotriene receptor 1 (CysLT1R) antagonist, on the impairment of learning and memory formation induced by Aß and the probable underlying electrophysiological and molecular mechanisms. We found that bilateral intrahippocampal injection of Aß1₋42 resulted in a significant decline of spatial learning and memory of mice in the Morris water maze (MWM) and Y-maze tests, together with a serious depression of in vivo hippocampal long-term potentiation (LTP) in the CA1 region of the mice. Importantly, this treatment caused significant increases in CysLT1R expression and subsequent NF-κB signaling, caspase-3 activation and Bcl-2 downregulation in the hippocampus or prefrontal cortex. Oral administration of pranlukast at 0.4 or 0.8 mg/kg for 4 wk significantly reversed Aß1₋42-induced impairments of cognitive function and hippocampal LTP in mice. Furthermore, pranlukast reversed Aß1₋42-induced CysLT1R upregulation, and markedly suppressed the Aß1₋42-triggered NF-κB pathway, caspase-3 activation and Bcl-2 downregulation in the hippocampus and prefrontal cortex in mice. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay confirmed its presence in the brain after oral administration of pranlukast in mice. These data disclose novel findings about the therapeutic potential of pranlukast, revealing a previously unknown therapeutic possibility to treat memory deficits associated with AD.

Benefit finding in individuals undergoing maintenance hemodialysis in Shanghai: a latent profile analysis.

Objective: This multi-center cross-sectional study aimed to delineate latent profiles of benefit finding (BF) in individuals undergoing maintenance hemodialysis (MHD) in Shanghai and examine associations between these BF profiles, social support, and coping style. Methods: A total of 384 individuals undergoing MHD (mean age = 57.90, SD = 13.36) were assessed using the Benefit Finding Scale, Simplified Coping Style Questionnaire, and Perceived Social Support Scale. Latent profile analysis (LPA) identified distinct BF categories. Analysis of variance (ANOVA) evaluated the correlation between BF groups and demographic variables, while the relationship between BF, social support, and coping style was tested through correlation and multiple regression analyses. Results: LPA identified three BF groups: rich BF (54.17%), moderate BF (41.14%), and poor BF (4.69%). Regression analyses indicated that positive coping and social support are protective factors for BF. Additionally, older age and heightened understanding of MHD correlated with higher BF levels. Conclusion: The findings highlighted the importance of recognizing different BF profiles in individuals on MHD and working toward promoting BF levels in the rich BF and moderate BF groups, while helping the poor BF group to identify and address their challenges. Medical professionals should consider interventions tailored to individual psychological profiles to improve mental health and quality of life outcomes in this population.

Pioglitazone ameliorates memory deficits in streptozotocin-induced diabetic mice by reducing brain ß-amyloid through PPARγ activation.

AIM: To examine the effects of pioglitazone, a PPARγ agonist, on memory performance and brain amyloidogenesis in streptozotocin (STZ)-induced diabetic mice. METHODS: ICR male mice were injected with STZ (150 mg/kg, iv) to induce experimental diabetes. Pioglitazone (9 and 18 mg·kg(-1)·d(-1), po) was administered for 6 weeks. Passive avoidance and Morris water maze (MWM) tests were used to evaluate cognitive function. The blood glucose and serum insulin levels were detected using the glucose oxidase method and an ELISA assay, respectively. ß-amyloid (Aß), ß-amyloid precursor protein (APP), ß-amyloid precursor protein cleaving enzyme 1 (BACE1), NF-κB p65, the receptor for advanced glycation end products (RAGE) and PPARγ in the brains were analyzed using Western blotting assays. RESULTS: The STZ-induced diabetic mice characterized by hyperglycemia and hypoinsulinemia performed poorly in both the passive avoidance and MWM tests, accompanied by increased Aß1-40/Aß1-42, APP, BACE1, NF-κB p65 and RAGE levels and decreased PPARγ level in the hippocampus and cortex. Chronic pioglitazone treatment significantly ameliorated the memory deficits and amyloidogenesis of STZ-induced diabetic mice, and suppressed expression of APP, BACE1, RAGE and NF-κB p65, and activated PPARγ in the hippocampus and cortex. However, pioglitazone did not significantly affect blood glucose and insulin levels. CONCLUSION: Pioglitazone ameliorates memory deficits in STZ-induced diabetic mice by reducing brain Aß level via activation of PPARγ, which is independent of its effects on blood glucose and insulin levels. The results suggest that pioglitazone may be used for treating the cognitive dysfunction in type 1 diabetes mellitus.

[On-line Measurement of Trace Elements in PM2.5 in Winter in Urban Taiyuan, China: Levels and Source Apportionment].

In order to better identify the sources of PM2.5 in Taiyuan, hourly concentrations of 13 trace elements (K, Ca, Ba, Cr, Mn, Fe, Cu, Ni, Zn, As, Se, Pb, and Sr) in PM2.5 were monitored at an urban site in Taiyuan from January 1 to 29, 2022. The pollution characteristics of trace elements were analyzed and sources were apportioned using positive matrix factorization (PMF). The results showed that the average concentration of 13 total trace elements was (3901.6±2611.2) ng·m-3, which accounted for (7.1±7.7)% of PM2.5. The three dominant elements were Fe[(1319.5±1003.5 ng·m-3)], Ca[(1181.0±1241.6 ng·m-3)], and K[(883.3±357.3 ng·m-3)]. The average concentrations of Cr(Ⅵ) (4.6 ng·m-3) and As (11.2 ng·m-3) exceeded the guideline values of the Chinese National Ambient Air Quality Standard (GB 3095-2012) and the World Health Organization. Fugitive dust, vehicle emissions, industry, stainless-steel production, biomass burning and waste incineration, residential coal combustion, and industrial coal combustion were identified by the PMF model, which accounted for 45.5%, 1.4%, 15.8%, 23.7%, 5.5%, and 8.1%, respectively, of the total elements.Compared with those during the stages of pollution development and dissipation, the contributions of industrial coal combustion, residential coal combustion, and biomass burning and waste incineration to the total elements during the pollution maintenance stage of the PM2.5 pollution episode increased significantly, contributing 11.8%, 7.1%, and 28.1%, respectively, of the total elements. These results could provide scientific references for the refined source apportionment of PM2.5 in other areas.

The analysis of low-dose glucocorticoid maintenance therapy in patients with primary nephrotic syndrome suffering from COVID-19.

Objectives: This study aimed to describe the effects of low-dose (prednisolone acetate 2.5-7.5 mg/day) glucocorticoids (GCs) maintenance therapy in patients with primary nephrotic syndrome (NS) suffering from coronavirus disease 2019 (COVID-19). Methods: A single-center retrospective study of NS patients with COVID-19 infection in Zhongda Hospital Affiliated to Southeast University from 1 February 2022 to 31 March 2023 was conducted. All enrolled patients underwent renal biopsy for the pathological diagnosis and reached complete remission (CR) or near-CR before COVID-19 infection. According to the maintained therapy regimen, patients were divided into low-dose GCs group and non-GCs group. Results: A total of 125 patients were enrolled in the study. Their median age was 46.0 ± 15.6 years, and the median value of 24-h urine protein was 0.77 g. The majority of these patients received treatment for more than 6 months, with a significant portion achieving CR (29.6%) or near-CR (43.2%). The leading cause of NS was membranous nephropathy (52%). There were no significant differences in the baseline characteristics between low-dose GCs and non-GCs group. As compared to those in the non-GCs group, patients receiving low-dose GCs treatment showed less fatigue or muscle weakness, smell disorder, palpitations, decreased appetite, taste disorder, dizziness, sore throat or difficult to swallow and fever (p < 0.05). Moreover, patients in the low-dose GCs group were with higher median quality of life scores (85.0) than in the non-GCs group (p = 0.001). Further serum inflammatory factor analysis indicated that interleukin-6 (IL-6) levels in the non-GCs group were significantly higher than that in the low-dose GCs group (p < 0.05). Conclusion: Patients with NS in low-dose GCs maintenance therapy stage showed milder symptom, higher quality of life and decreased serum IL-6 levels compared to those, who were not on GCs maintenance therapy. These results suggest the beneficial effect of low-dose GCs therapy in NS patients with CR/near-CR suffering from COVID-19 infection.

Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone.

AIM: To investigate the effect of genistein on bone homeostasis in mandibular subchondral bone of rats. METHODS: Female SD rats were administered with genistein (10 and 50 mg/kg) or placebo by oral gavage for 6 weeks. Then the animals were sacrificed, and histomorphology and micro-structure of mandibular condyle were examined using HE staining and micro-CT analysis, respectively. The expression levels of alkaline phosphatase (ALP), osteocalcin (OC), osteoprotegerin (OPG), the receptor activator of nuclear factor κB ligand (RANKL) and estrogen receptors (ERs) in mandibular condyle were detected using real-time PCR. Cultured osteoblasts were prepared from rat mandibular condyle for in in vitro study. The cells were treated with genistein (10(-7) or 10(-4) mol/L) for 48 h. The expression of the bone homeostasis-associated factors and estrogen receptors (ERs) was detected using real-time PCR, and ER silencing was performed. RESULTS: At both the low- and high-doses, genistein significantly increased the bone mineral density (BMD) and bone volume, and resulted in thicker subchondral trabecular bone in vivo. In both in vivo and in vitro study, the low-dose genistein significantly increased the expression of ALP, OC and OPG, but decreased the expression of RANKL and the RANKL/OPG ratio. The high-dose genistein decreased the expression of all these bone homeostasis-associated factors. Both the low and high doses of genistein significantly increased the expression of ERß, while ERα expression was increased by the low dose genistein and decreased by the high dose genistein. ERß silencing abrogated most of the effects of genistein treatment. CONCLUSION: In rat mandibular condylar subchondral bone, low-dose genistein increases bone formation and inhibit bone resorption, while excess genistein inhibits both bone formation and resorption. The effects of genistein were predominantly mediated through ERß.

[Vertigo due to enlarged vestibule with lateral semicircular canal dysplasia: an analysis of clinical characteristics].

OBJECTIVE: To explore the clinical characteristics and possible pathological mechanisms of vertigo due to enlarged vestibule with lateral semicircular canal dysplasia. METHODS: A retrospective review was conducted for 5 cases of peripheral vertigo due to enlarged vestibule with lateral semicircular canal dysplasia. Their characteristics of medical history, precipitating factors, course of vertigo, auditory tests, vestibular tests and imaging examine results were analyzed. RESULTS: The clinical characteristics were as follows. (1) Specifics of medical history: 4 cases suffered delays in gross motor development and potential equilibrium dysfunctions. One case failed to recount an earlier medical history, but could maintain normal hearing and vestibular functions for a long time in adulthood. (2) Most cases could identify the precipitating factors of initial attacks, such as head-bumping, nose-blowing and constipation, etc. resulting in sudden rises of intracranial or abdominal pressures. (3) Paroxysmal vertigo and progressive hearing loss were mimicking Meniere disease or large vestibular aqueduct syndrome. But its course of vertigo was different from those of Meniere disease and large vestibular aqueduct syndrome with regards to hearing levels and audiograms. (4) Some cases had positional vertigo. But the results of Dix-Hallpike and Roll tests were different from benign paroxysmal positioning vertigo (BPPV). (5) The inner ear imaging showed enlarged vestibule with lateral semicircular canal dysplasia. CONCLUSION: The enlarged vestibule with lateral semicircular canal dysplasia is a rare etiology of peripheral vertigo. The history of delays in gross motor development and potential equilibrium dysfunctions in childhood may offer important diagnostic clues. And audiological and vestibular tests, high-resolution computed tomography and magnetic resonance may help to ascertain the diagnosis.

Spinal high-mobility group box 1 contributes to mechanical allodynia in a rat model of bone cancer pain.

Mechanisms underlying bone cancer-induced pain are largely unknown. Previous studies indicate that neuroinflammation in the spinal dorsal horn is especially involved. Being first reported as a nonhistone chromosomal protein, high-mobility group box 1 (HMGB1) is now implicated as a mediator of inflammation. We hypothesized that HMGB1 could trigger the release of cytokines in the spinal dorsal horn and contribute to bone cancer pain. To test this hypothesis, we first built a bone cancer pain model induced by intratibal injection of Walker 256 mammary gland carcinoma cells. The structural damage to the tibia was monitored by radiological analysis. The mechanical allodynia was measured and the expression of spinal HMGB1 and IL-1beta was evaluated. We observed that inoculation of cancer cells, but not heat-killed cells, induced progressive bone destruction from 9 d to 21 d post inoculation. Behavioral tests demonstrated that the significant nociceptive response in the cancer cells-injected rats emerged on day 9 and this kind of mechanical allodynia lasted at least 21 d following inoculation. Tumor cells inoculation significantly increased HMGB1 expression in the spinal dorsal horn, while intrathecal injecting a neutralizing antibody against HMGB1 showed an effective and reliable anti-allodynia effect with a dose-dependent manner. IL-1beta was significantly increased in cancer pain rats while intrathecally administration of anti-HMGB1 could decrease IL-1beta. Together with previous reports, we predict that bone cancer induces HMGB1 production, enhancing spinal IL-1beta expression and thus modulating spinal excitatory synaptic transmission and pain response.

Glucocorticoid receptor expression and glucocorticoid therapeutic effect in nasal polyps.

PURPOSE: To investigate the expression and quantity of glucocorticoid receptor-alpha and -beta in polyp tissues taken from the patients treated were subsequently treated with topical glucocorticoid (GC). METHODS: Eighty patients with nasal polyps were initially enrolled in the study. All polyp specimens were obtained prior to treatment. Patients then received daily topical GC spray treatment for one month. Polyp specimens were tested for glucocorticoid receptor (GR) GR-alpha and GR-beta mRNA expression using fluorescent quantitative-reverse transcription-polymerase chain reaction (FQ-RT-PCR). Thirty healthy nasal mucosa tissue samples were tested at the same time. RESULTS: Forty patients finished the study and were divided into two groups: GC-sensitive (n=26) and GC-insensitive (n=14), according to treatment results. GR-beta mRNA expression in the nasal polyp tissues of the GC-insensitive group (5.72+/-0.58x10(2) copies/microg) was higher than that in the GC-sensitive group (4.82+/-0.28x10(2) copies/microg, P < 0.05) and in the normal nasal mucosa group (4.44+/-0.35x10(2) copies/microg, P < 0.01). There was also a difference in the relative expression of GR-alpha and GR-beta between the GC-sensitive group (GR-alpha/GR-beta= 829.42+/-67.36) and the GC-insensitive group (535.7+/-89) (P < 0.01). CONCLUSION: GR-beta mRNA was highly expressed in patients with nasal polyps. Down- regulation of GR-alpha mRNA suggests the existence of glucocorticoid insensitivity. Expression of GR-beta may plays an important role in the evaluation of the glucocorticoid therapeutic effect in patients with nasal polyps.

Methanol extract of Phellodendri cortex alleviates lipopolysaccharide-induced acute airway inflammation in mice.

BACKGROUND AND AIM: The effects of methanol extract of Phellodendri cortex on acute airway inflammation induced by intranasal administration of lipopolysaccharide (LPS, 300mug/kg) were investigated in female BALB/c mice. MATERIALS AND METHODS: At 2 h after LPS exposure, mice were treated orally with methanol extract of Phellodendri cortex (100, 200 and 400 mg/kg). At the end of this study, bronchoalveolar lavage fluids (BALF) were collected and number of total cells, macrophages and neutrophils, protein concentration were analyzed. Tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein (MIP-2), IL-10 levels and nitric oxide (NO) production in BALF were also determined. RESULTS: Methanol extract of Phellodendri cortex dose-dependently alleviated LPS-induced acute airway inflammation via decreasing the infiltration of inflammatory cells and the release of inflammatory mediators. CONCLUSION: The relief of airway inflammation provides a possible therapeutic application of Phellodendri cortex for the treatment of infectious pulmonary diseases.

[The clinical characteristics of the benign paroxysmal positional vertigo associated with Meniere's disease].

OBJECTIVE: To explore the clinical characteristics of the benign paroxysmal positional vertigo (BPPV) associated with Meniere's disease (MD) in retrospect in an effort to improve the diagnosis and efficacy of treatment. METHOD: Fifteen cases (1 male and 14 female, aged 46 to 68 years old) of BPPV associated with MD from July 2007 to June 2009 were retrospectively analyzed. Patient clinically characterized with positional paroxysmal vertigo were diagnosed as MD by ECochG and glycerol test and were confirmed as BPPV associated with MD by Dix Hallpike test or roll test. They were treated with Epley maneuver or Barbecue rol maneuver according to the type of BPPV, and the efficacy was evaluated. RESULT: (1) Most cases involved female patients in this study; (2) BPPV occurred after MD in al of the cases, of which 13 cases were posterior semicircular canal lithiasis (9 cases in the same ear, 2 in the other and 2 in both) and 2 cases were horizontal semicircular canal lithiasis (cupula lithiasis in the same ear); (3) in this study, 10 patients were cured after 3-4 times of posture treatment (66.7%), 4 patients were cured after 5 times and 1 patient received endolymphatic sac decompression because of recurrent vertigo. CONCLUSION: (1) BPPV can result from MD, for which a possible mechanism may be the hydrolabyrinth that lead to eardust falling off. (2) Most cases of BPPV occurred in the posterior semicircular canal in the same ear. Most cases in incidence rate have obvious sexual bias in female. (3) Eardust reposition is an effective treatment for BPPV caused by MD; while it is refractory compared to ordinary BPPV and require multiple treatments, which may be related to the recurrence of hydrolabyrinth.

Qingyi decoction protects against myocardial injuries induced by severe acute pancreatitis.

BACKGROUND: We studied the protective effects of Qingyi decoction (QYD) (a Traditional Chinese Medicine) against severe acute pancreatitis (SAP)-induced myocardial infarction (MI). AIM: To study the function and mechanism of QYD in the treatment of myocardial injuries induced by SAP. METHODS: Ultrasonic cardiography, hematoxylin and eosin staining, immunohistochemistry, qRT-PCR, western blot, enzyme-linked immunosorbent assays, and apoptosis staining techniques were used to determine the effects of QYD following SAP-induced MI in Sprague-Dawley rats. RESULTS: Our SAP model showed severe myocardial histological abnormalities and marked differences in the symptoms, mortality rate, and ultrasonic cardiography outputs among the different groups compared to the control. The expression of serum cytokines [interleukin (IL)-1ß, IL-6, IL-8, IL-12, amyloid ß, and tumor necrosis factor-α] were significantly higher in the SAP versus QYD treated group (P < 0.05 for all). STIM1 and Orai1 expression in myocardial tissue extracts were significantly decreased post QYD gavage (P < 0.001). There was no significant histological difference between the 2-aminoethyl diphenylborinate inhibitor and QYD groups. The SAP group had a significantly higher apoptosis index score compared to the QYD group (P < 0.001). CONCLUSION: QYD conferred cardio-protection against SAP-induced MI by regulating myocardial-associated protein expression (STIM1 and Orai1).

Upregulation of RAGE at the blood-brain barrier in streptozotocin-induced diabetic mice.

Deposition of amyloid-beta peptide (Abeta) in the brain of diabetes is poorly understood. The receptor for advanced glycation end products (RAGE) at the blood-brain barrier (BBB) is critical for regulation of Abeta homeostasis in the brain. In this studies, we used streptozotocin-induced diabetic mice to observe the expression of RAGE at the BBB by Western blot and immunocytochemical analysis, and the in vivo blood-to-brain influx transport of (125)I-Abeta(1-) (40) using the permeability surface area product (PS) and brain capillary uptake. In the diabetic mice with hyperglycemia (>16.0 mmol/L) at 6 weeks, RAGE expression at the BBB was significantly upregulated, no significant changes of RAGE levels were found at 1 and 3 weeks after diabetes induction. The data of PS and brain capillary uptake for Abeta showed significant RAGE-dependent transport of Abeta across the BBB and substantial RAGE-dependent brain capillary uptake at 6 weeks after diabetes induction. We conclude that the upregulation of RAGE at the BBB contributes to cerebral Abeta deposition in the diabetes.

Glutathione depletion upregulates P-glycoprotein expression at the blood-brain barrier in rats.

OBJECTIVES: Glutathione (GSH) depletion has been implicated in the pathogenesis of neurological diseases. During GSH depletion, cells of the blood-brain barrier are subjected to chronic oxidative stress. Using an in-vivo system, we have investigated whether glutathione depletion changed expression of P-glycoprotein at the blood-brain barrier in rats. METHODS: Diethyl maleate was intraperitoneally injected to induce GSH depletion in rats. P-glycoprotein expression at the blood-brain barrier was examined by Western blotting and RT-PCR, and its function was assessed by measuring the brain-to-plasma concentration ratios (Kp values) of rhodamine 123 (Rh123). Evans Blue dye was used as a blood-brain barrier indicator for examining the extravasation from the blood to the brain. KEY FINDINGS: Four hours after treatment of rats with diethyl maleate, the brain GSH content significantly reduced. The mdr1a mRNA expression at the blood-brain barrier was upregulated, whereas no significant change in mdr1b mRNA expression was found. The P-glycoprotein level was significantly increased compared with control rats. At the same time, the Kp values of Rh123 suggested that function of P-glycoprotein was significantly enhanced at the blood-brain barrier in rats with GSH depletion induced by diethyl maleate. No significant difference of the Evans Blue dye concentration in the brain cortex was found between GSH depletion rats and control rats. Treatment of rats with N-acetylcysteine decreased P-glycoprotein upregulation induced by diethyl maleate. CONCLUSIONS: The oxidative stress induced by GSH depletion played a positive role in the regulation of function and expression of P-glycoprotein at the blood-brain barrier in rats.

Relationship between insulin sensitivity index and cognitive function in diet-induced insulin resistant rats.

Clinical and animal studies have revealed significant cognitive impairment in type II diabetic subjects. However, whether there is a relationship between insulin resistance and cognitive function is poorly understood. In the present study, we used a high fat diet to induce insulin resistance (IR) in rats, insulin sensitivity index (ISI) (= FINS x FPG/22.5) to assess the extent of insulin resistance and the Morris Water Maze Task to judge cognitive function. The relationship between insulin sensitivity index and cognitive function was determined by analysing the correlation between ISI and the time rat spent in targeted quadrant, as well as between ISI and the times the rat swam across the very point where a platform was previously placed, using Pearson's method. Perfect negative correlation between ISI and cognitive function existed when ISI fell within a certain range, which indicates that insulin resistance is associated with cognitive function impairment in some cases where ISI might be an indicator.

The multifaceted mechanisms for coffee's anti-tumorigenic effect on liver.

Epidemiological studies have found an inverse association between coffee consumption and the risk of liver cancer. Animal data support such a chemopreventive effect of coffee. Substantial research has been devoted to the identification of coffee components that may be responsible for these beneficial effects. Based on the current available literature, three major components, i.e. coffee diterpenes cafestol and kahweol (C+K), caffeine and chlorogenic acid contribute to the beneficial effects. These components induce phase II detoxifying and antioxidant enzymes as well as inhibit the expression or decrease the activity of phase I activating enzymes thus prevent carcinogenesis. These components target different stages of a common pathway, Kelch-like ECH-associated protein 1 (Keap1)--NF-E2-related factor-2 (Nrf2)--antioxidant-responsive-element (ARE) signal pathway thus alter the ARE-dependent expression of genes needed in the anti-tumorigenic effects.