Quercetin protects islet ß-cells from oxidation-induced apoptosis via Sirt3 in T2DM.

OBJECTIVES: Sirt3 may regulate ROS production and might be involved in ß-cell apoptosis, which plays an important role in the progression of type 2 diabetes mellitus (T2DM). Quercetin is a potent anti-oxidative bioflavonoid, but its effects on T2DM remain to be explored. This study aimed to investigate the effects of quercetin on ß-cell apoptosis and explore its mechanisms. MATERIALS AND METHODS: The effects of quercetin were conducted on db/db mice and INS1 cells. Fasting blood glucose was determined by the colorimetric method, serum insulin was measured by enzyme-linked immunosorbent assay (ELISA). Meanwhile, Sirt3 in INS1 cells was knocked down by plasmid transfection. The antioxidant proteins (SOD2 and CAT), apoptosis proteins (cleaved Caspase-3, Bax, and BCL-2), and Sirt3 protein in pancreases and INS1 cells were determined by western blotting. RESULTS: When INS1 cells and diabetic mice were treated with quercetin, the levels of SOD2, CAT, and Sirt3 proteins were increased, the levels of cleaved Caspase-3 and the ratio of Bax to BCL-2 were decreased at different degrees, along with reduced blood glucose levels and elevated insulin levels in diabetic mice. When Sirt3 was knocked down in INS1 cells, increase of two antioxidants and decrease of cell apoptosis generated by quercetin could not occur. CONCLUSION: Quercetin protected islet ß-cells from oxidation-induced apoptosis via Sirt3 in T2DM, which would be beneficial to develop new strategies for preventing ß-cell failure in T2DM.

Illustration of a number of atypical computed tomography manifestations of active pulmonary tuberculosis.

Tuberculosis is a serious public health challenge facing mankind and one of the top ten causes of death. Diagnostic imaging plays an important role, particularly for the diagnosis and treatment planning of tuberculosis patients with negative microbiology results. This article illustrates a number of atypical computed tomography (CT) appearances of pulmonary tuberculosis (PTB), including (I) clustered micronodules (CMNs) sign; (II) reversed halo sign (RHS); (III) tuberculous pneumatocele; (IV) hematogenously disseminated PTB with predominantly diffuse ground glass opacity manifestation; (V) hematogenously disseminated PTB with randomly distributed non-miliary nodules; (VI) PTB changes occur on the background of emphysema or honeycomb changes of interstitial pneumonia; and (VII) PTB manifesting as organizing pneumonia. While the overall incidence of PTB is decreasing globally, the incidence of atypical manifestations of tuberculosis is increasing. A good understanding of the atypical CT imaging changes of active PTB shall help the diagnosis and differential diagnosis of PTB in clinical practice.

Bedaquiline-containing regimens in patients with pulmonary multidrug-resistant tuberculosis in China: focus on the safety.

BACKGROUND: World Health Organization recommends countries introducing new drug and short treatment regimen for drug resistant tuberculosis (DR-TB) should develop and implement a system for active pharmacovigilance that allows for detection, reporting and management of adverse events. The aim of the study is to evaluate the frequency and severity of adverse events (AEs) of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active drug safety monitoring (aDSM) system of New Drug Introduction and Protection Program (NDIP). METHODS: AEs were prospectively collected with demographic, bacteriological, radiological and clinical data from 54 sites throughout China at patient enrollment and during treatment between February, 2018 and December, 2019. This is an interim analysis including patients who are still on treatment and those that have completed treatment. A descriptive analysis was performed on the patients evaluated in the cohort. RESULTS: By December 31, 2019, a total of 1162 patients received bedaquiline-containing anti-TB treatment. Overall, 1563 AEs were reported, 66.9% were classified as minor (Grade 1-2) and 33.1% as serious (Grade 3-5). The median duration of bedaquiline treatment was 167.0 [interquartile range (IQR): 75-169] days. 86 (7.4%) patients received 36-week prolonged treatment with bedaquiline. The incidence of AEs and serious AEs was 47.1% and 7.8%, respectively. The most frequently reported AEs were QT prolongation (24.7%) and hepatotoxicity (16.4%). There were 14 (1.2%) AEs leading to death. Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 3.1% (32/1044) experienced a post-baseline QTcF ≥ 500 ms, and 15.7% (132/839) had at least one change of QTcF ≥ 60 ms from baseline. 49 (4.2%) patients had QT prolonged AEs leading to bedaquiline withdrawal. One hundred and ninety patients reported 361 AEs with hepatotoxicity ranking the second with high occurrence. Thirty-four patients reported 43 AEs of hepatic injury referred to bedaquiline, much lower than that referred to protionamide, pyrazinamide and para-aminosalicylic acid individually. CONCLUSIONS: Bedaquiline was generally well-tolerated with few safety concerns in this clinical patient population without any new safety signal identified. The mortality rate was generally low. These data inform significant positive effect to support the WHO recent recommendations for the wide use of bedaquiline.

The Diagnostic Accuracy of Magnetic Resonance Imaging in Restaging of Rectal Cancer After Preoperative Chemoradiotherapy: A Meta-Analysis and Systematic Review.

OBJECTIVE: To evaluate the overall diagnostic value of magnetic resonance imaging (MRI) in restaging of rectal cancer after preoperative chemoradiotherapy based on qualified studies. METHODS: PubMed, Cochrane, and EMBASE database were searched by the index words to identify the qualified studies, and relevant literature sources were also searched. The latest research was done in April 2019. Heterogeneity of the included studies was tested, which was used to select proper effect model to calculate pooled weighted sensitivity, specificity, and diagnostic odds ratio (DOR). Summary receiver operating characteristic (SROC) analyses were also performed. RESULT: Nineteen studies with 1262 patients were involved in the meta-analysis exploring the diagnostic accuracy of MRI for rectal cancer. The diagnostic accuracy of MRI in T3-T4 rectal cancer was as follows: sensitivity, 81% (95% confidence interval [CI], 67%-90%); specificity, 67% (95% CI, 51%-80%); positive likelihood ratio, 2.48 (95% CI, 1.57-3.91); negative likelihood ratio, 0.28 (95% CI, 0.15-0.52); global DOR, 6.86 (95% CI, 3.07-15.30); the area under the SROC was high (0.81; 95% CI, 0.78-0.84). The diagnostic accuracy of MRI in lymphatic metastasis of rectal cancer was as follows: sensitivity, 77% (95% CI, 65%-86%); specificity, 77% (95% CI, 63%-87%); positive likelihood ratio, 3.40 (95% CI, 2.07-5.59); negative likelihood ratio, 0.30 (95% CI, 0.20-0.45); DOR, 10.81 (95% CI, 4.99-23.39); area under the SROC was high (0.84; 95% CI, 0.80-0.87). CONCLUSIONS: This study provides a systematic review and meta-analysis of diagnostic accuracy studies of MRI for rectal cancer. The results indicate that MRI is a highly accurate diagnostic tool for rectal cancer T3-T4 staging and N staging but sensitivity and specificity are not high.

The association between pulmonary function impairment and colon inflammation in ulcerative colitis patients: A scientific basis for exterior-interior correlation between lung and large intestine.

OBJECTIVE: To investigated the involvement of pulmonary function impairment in ulcerative colitis (UC), to explore a scientific basis for the Chinese medicine (CM) theory of exterior-interior correlation between Lung (Fei) and Large intestine (Dachang). METHODS: Totally 120 patients with a diagnosis of UC were recruited and the demographics, clinical data, and blood samples were collected. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) concentrations were measured. Every patient accepted pulmonary function test and took chest radiograph (CXR).> RESULTS: Pulmonary function abnormalities were present in 72 of 120 patients. The median (interquartile range) vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), carbon monoxide diffusion capacity (DLCO) of lung, total lung capacity (TLC) and functional residual volume (FRV) were decreased in distal UC and pancolitis compared with ulcerative prochitis (P <0.0005). Male patients had increased VC, FEV1/FVC, and residual volume (RV)/TLC compared with female (P <0.0005), but decreased DLCO and carbon monoxide iffusion capacity (KCO) of lung/alveolar ventilation (P <0.0005). Age was strongly correlated with RV (Spearman rank correlation coefficient (rs)=-0.57,P <0.0001), and RV/TLC (rs=0.48,P<0.0001). Age was also correlated with FEV1/FVC (rs=-0.29, P=0.001), forced expiratory flow in 75% vital capacity (FEF75%, rs=-0.20, P=0.03), DLCO (rs=-0.21, P=0.02), TLC (rs=-0.25, P=0.006), and FRV (rs=-0.28, P=0.002). The course of disease was correlated with FEF75% (rs=-0.18, P=0.049) and KCO (rs=-0.19, P=0.036). Chest radiograph abnormalities were presented in 38 of 120. Pulmonary symptoms were presented in 10 of 120. Other extraintestinal complications were presented in 21 of 120. CONCLUSIONS: Pulmonary function impairment was more frequently than other extraintestinal complications in UC patients, which may be affected by sex, age, extent and course of disease. These results may be a scientific basis for the theory of exterior-interior correlation between Lung and Large intestine.

Jak2/Stat1 pathway mediated tetrahydrobiopterin up-regulation contributes to nitric oxide overproduction in high-glucose cultured rat mesangial cells.

Nitric oxide (NO) is crucial for the progression of early diabetic nephropathy (DN). It is important to clarify the mechanism for the production of NO in mesangial cells (MCs). In this study, the amounts/activities of related factors such as reactive oxygen species (ROS), NO, 3 isoforms of nitric oxide synthase (NOS), tetrahydrobiopterin (BH4), GTP cyclohydrolase I (GTPCH I), Jak2, and Stat1 were determined using high-glucose cultured rat MCs. The results showed that the production of BH4 under oxidative stress was strongly stimulated by its rate-limiting enzyme GTP cyclohydrolase, which increased the expression and activity of inducible NOS to facilitate NO synthesis. Furthermore, the relative quantities of activated-Jak2 and activated-Stat1 were increased. Therefore, Jak2/Stat1 pathway mediated BH4 up-regulation can contribute to excessive NO in high-glucose cultured MCs. Our results will be helpful for screening new targets to improve the therapy for early DN.

Extracts of black bean peel and pomegranate peel ameliorate oxidative stress-induced hyperglycemia in mice.

Oxidative stress has a central role in the progression of diabetes mellitus (DM), which can directly result in the injury of islet ß cells and consequent hyperglycemia. The aim of the present study was to evaluate the possible protective effects of black bean peel extract (BBPE), pomegranate peel extract (PPE) and a combination of the two (PPE + BBPE) on streptozotocin-induced DM mice. Oxidative stress was assessed by the levels of total antioxidative capability and glutathione in the serum. Fasting blood glucose and insulin levels, as well as the pancreas weight index and the histological changes in the pancreas, were also determined. The results showed that, after fours weeks of treatment with PPE, BBPE or PPE + BBPE, DM mice showed, to different degrees, a decrease in blood glucose, increases in insulin secretion and the pancreas weight index, and an increase in antioxidative activity. These changes were particularly evident in the DM mice subjected to the combined intervention strategy of PPE + BBPE. The histological findings indicated that the injury to the pancreatic islets in DM mice was also ameliorated following treatment. In conclusion, PPE and BBPE, particularly the combination of the two, have the ability to ameliorate hyperglycemia by inhibiting oxidative stress-induced pancreatic damage; this finding may be useful in the prevention and treatment of DM.

[Correlation between pulmonary function impairment and levels of alpha1-antitrypsin in serum and colon of ulcerative colitis patients: a clinical research].

OBJECTIVE: To explore the mechanism of pulmonary involvement in ulcerative colitis (UC) patients by observing the correlation between pulmonary functions and levels of alpha1-antitrypsin (A1AT) in serum and colon tissue in UC patients. METHODS: Totally 90 patients with confirmed UC were assigned to different groups according to the extent of disease, the disease activity, the staging of severity, and course of disease. The serum level of A1AT in UC patients with different extent of disease, the disease activity, the staging of severity, and course of disease were compared. And 30 healthy volunteers were recruited as the control group. The serum renal and hepatic functions, pulmonary functions, and serum levels of A1AT were detected in the UC group and the control group. The correlation between A1AT and each pulmonary function index in UC patients was analyzed. The A1AT content in the colon tissue was detected with immunohistochemical assay in 20 UC patients as well as in 10 healthy volunteers. RESULTS: Of the 90 UC patients, 54 patients were accompanied with pulmonary function abnormality (60.0%), and 24 with extraintestinal manifestations (26.7%). Compared with the control group, the serum level of A1AT was significantly lower in the UC group (P < 0.05). The serum level of A1AT was significantly higher in those with proctitis than in those with distal colonitis and pancolitis (P < 0.05). The serum level of A1AT was lower in patients with the course of disease 5 years and more than 5 years than in those with the course of disease less than 5 years (P < 0.05). Vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1.0), total lung capacity (TLC), function residual volume (FRV), and the ratio of diffusion capacity for carbon monoxide of lung (DLCO) were much lower in those with proctitis than in those with distal colonitis and pancolitis (P < 0.05). The ratio of FVC was negatively linear correlated with the course of disease (r = -0.23, P = 0.018). There was a positive correlation between the serum level of A1AT and peak expiratory flow (PEF) (r = 0.22, P = 0.03). The level of A1AT in the colon tissue was obviously lower in the UC patients than in those of the control group (P < 0.05). Mild and moderate UC patients had increased levels of A1AT in the colon tissue, when compared with severe UC patients (P < 0.05). The level of A1AT in the colon tissue was higher in those with proctitis than in those with distal colonitis and pancolitis (P < 0.05). CONCLUSIONS: The prevalence of pulmonary function impairment was higher than other extraintestinal manifestations in UC patients. The pulmonary function test was helpful to screen the pulmonary impairment of UC patients. The A1AT level in the serum and the colon tissue obviously decreased in UC patients, indicating the pulmonary function impairment of UC patients might manifest as decreased A1AT levels correlated chronic airway inflammation, remodeling of airway, and obstructive changes.

Efficacy of Metarhizium anisopliae isolate MAX-2 from Shangri-la, China under desiccation stress.

BACKGROUND: Metarhizium anisopliae, a soil-borne entomopathogen found worldwide, is an interesting fungus for biological control. However, its efficacy in the fields is significantly affected by environmental conditions, particularly moisture. To overcome the weakness of Metarhizium and determine its isolates with antistress capacity, the efficacies of four M. anisopliae isolates, which were collected from arid regions of Yunnan Province in China during the dry season, were determined at different moisture levels, and the efficacy of the isolate MAX-2 from Shangri-la under desiccation stress was evaluated at low moisture level. RESULTS: M. anisopliae isolates MAX-2, MAC-6, MAL-1, and MAQ-28 showed gradient descent efficacies against sterile Tenebrio molitor larvae, and gradient descent capacities against desiccation with the decrease in moisture levels. The efficacy of MAX-2 showed no significant differences at 35% moisture level than those of the other isolates. However, significant differences were found at 8% to 30% moisture levels. The efficacies of all isolates decreased with the decrease in moisture levels. MAX-2 was relatively less affected by desiccation stress. Its efficacy was almost unaffected by the decrease at moisture levels > 25%, but slowly decreased at moisture levels < 25%. By contrast, the efficacies of other isolates rapidly decreased with the decrease in moisture levels. MAX-2 caused different infection characteristics on T. molitor larvae under desiccation stress and in wet microhabitat. Local black patches were found on the cuticles of the insects, and the cadavers dried without fungal growth under desiccation stress. However, dark black internodes and fungal growth were found after death of the insects in the wet microhabitat. CONCLUSIONS: MAX-2 showed significantly higher efficacy and superior antistress capacity than the other isolates under desiccation stress. The infection of sterile T. molitor larvae at low moisture level constituted a valid laboratory bioassay system in evaluating M. anisopliae efficacy under desiccation stress.

SIRT5 desuccinylates and activates SOD1 to eliminate ROS.

Cu/Zn superoxide dismutase (SOD1) is a key antioxidant enzyme. Deficiency of SOD1 is associated with various human diseases, including cancer. Here, we report that SOD1 is succinylated and that succinylation decreases its activity. SIRT5 binds to, desuccinylates and activates SOD1. SOD1-mediated ROS reduction is increased when SIRT5 is co-expressed. Furthermore, mutation of the SOD1 succinylation site inhibits the growth of lung tumor cells. These results reveal a novel post-translational regulation of SOD1 by means of succinylation and SIRT5-dependent desuccinylation, which is important for the growth of lung tumor cells.

Up-regulation of glyoxalase 1 by mangiferin prevents diabetic nephropathy progression in streptozotocin-induced diabetic rats.

Advanced glycation endproducts (AGEs) and its precursor methylglyoxal are associated with diabetic nephropathy (DN). Mangiferin has many beneficial biological activities, including anti-inflammatory, anti-oxidative and anti-diabetic effects. We investigated the effect of mangiferin on DN and its potential mechanism associated with glyoxalase 1 (Glo-1), a detoxifying enzyme of methylglyoxal, in streptozotocin-induced rat model of DN. Diabetic rats were treated orally with mangiferin (15, 30, and 60 mg/kg) or distilled water for 9 weeks. Kidney tissues were collected for morphologic observation and the determination of associated biochemical parameters. The cultured mesangial cells were used to measure the activity of Glo-1 in vitro. Chronic treatment with mangiferin significantly ameliorated renal dysfunction in diabetic rats, as evidenced by decreases in albuminuria, blood urea nitrogen, kidney weight index, periodic acid-schiff stain positive mesangial matrix area, glomerular extracellular matrix expansion and accumulation, and glomerular basement membrane thickness. Meanwhile, mangiferin treatment caused substantial increases in the enzymatic activity of Glo-1 in vivo and in vitro, and protein and mRNA expression of Glo-1, reduced levels of AGEs and the protein and mRNA expression of their receptor (RAGE) in the renal cortex of diabetic rats. Moreover, mangiferin significantly attenuated oxidative stress damage as reflected by the lowered malondialdehyde and the increased glutathione levels in the kidney of diabetic rats. However, mangiferin did not affect the blood glucose and body weight of diabetic rats. Therefore, mangiferin can remarkably ameliorate DN in rats through inhibiting the AGEs/RAGE aix and oxidative stress damage, and Glo-1 may be a target for mangiferin action.

Suppression of methylglyoxal hyperactivity by mangiferin can prevent diabetes-associated cognitive decline in rats.

RATIONALE: Evidences indicate that methylglyoxal, a highly reactive metabolite of hyperglycemia, can enhance protein glycation, oxidative stress, or inflammation. Mangiferin, a polyphenol compound of C-glucoside, has many beneficial biological activities, including anti-inflammation, anti-oxidation, neuroprotection, cognitive enhancement, etc. Whether mangiferin alleviates diabetes-associated cognitive impairment is still unclear. OBJECTIVES: The present study was designed to investigate the effects of mangiferin on the behavioral deficits of diabetic rats induced by streptozotocin; the mechanisms associated with methylglyoxal toxicity are especially investigated. METHODS: Diabetic rats were treated with mangiferin (15, 30, and 60 mg/kg, p.o.) for 9 weeks. Cognitive performances were evaluated with the Morris water maze. Hippocampus and blood were obtained for evaluation of the effects of mangiferin on protein glycation, oxidative stress, and inflammation in diabetic state. RESULTS: Mangiferin significantly improved the behavioral performances of diabetic rats, evidenced by a decrease in escape latency as well as increases in numbers of crossing the platform and percentage of time spent in the target quadrant, which were accompanied by decreases in the levels of advanced glycation end-products and their receptor (RAGE), interleukin-1ß, TNF-α, and malondialdehyde and increases in the activity and expression of glyoxalase 1 as well as glutathione level in the hippocampus of diabetic rats. Furthermore, mangiferin produced a significant decrease in malondialdehyde level and increased glutathione level and superoxide dismutase activity in the serum of diabetic rats. CONCLUSIONS: This study demonstrates that mangiferin can markedly ameliorate diabetes-associated cognitive decline in rats, which is done likely through suppressing methylglyoxal hyperactivity (promoting protein glycation, oxidative stress, and inflammation) mediated noxious effects.

Study of the retinal imaging and output in premature baby under a computer-assisted binocular indirect ophthalmoscope.

PURPOSE: To explore a clear retinal imaging and output and enhance the development of retinopathy of prematurity (ROP) screening, which is safe and effective for ROP screening in premature infants. METHODS: A computer-assisted binocular indirect ophthalmoscope imaging and output system was equipped with camera and image processing hardware and connected to computers. The process of fundus examination was videotaped (photograph) and output. Simulated eyes were utilized to debug video head and acquire stable and clear fundus images by binocular indirect ophthalmoscope for premature infants. RESULTS: Fundus imaging output technique was sucessfully established. The common reasons of unclear imaging and corresponding solutions were summarized. This technique can capture and output stable and clear fundus images of premature infants. CONCLUSION: Assisted by hardware and software processing, a compute assisted binocular indirect ophthalmoscope imaging and output system was established, which can be used for screening, research, treatment and follow-up of ROP in premature babies to resolve the difficulty in obtaining clear fundus photograph.

[Study on the correlation between the pulmonary injury and the ET-1 serum level in ulcerative colitis patients].

OBJECTIVE: To study the correlation between the pulmonary injury and the ET-1 serum level in ulcerative colitis (UC) patients, and to study the mechanism for UC induced pulmonary injury. METHODS: Recruited were 90 UC outpatients from the clinics of Gastroenterology Department, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine from Nov. 2009 to Mar. 2011. The course of disease, disease range, serum ET-1 level of UC patients were observed and compared. The correlation between the serum ET-1 level and each pulmonary function index were studied [including vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC, peak expiratory flow (PEF), maximal mid expiratory flow (MMEF), maximal expiratory flow in 25%, 50%, 75% vital capacity (FEF25%, 50%, 75%), diffusion capacity for carbon monoxide of lung (DLCO), diffusion constant (KCO), total lung capacity (TLC), alveolar ventilation (VA), residual volume (RV), function residual volume (FRV), and RV/TLC]. Besides, another 30 healthy volunteers were enrolled as the control group. The pulmonary symptoms, chest X-ray, the lung function, the serum ET-1 level, and liver and kidney functions [including alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), serum creatinine (SCr) were compared between the UC group and the control group. RESULTS: Ten UC patients were accompanied with cough and chest distress (accounting for 11.1%), 25 with abnormal chest films (accounting for 27.8%), and 54 with pulmonary function abnormality (accounting for 60.0%). In the UC group ALT increased in 2 cases (2.2%) and AST increased in 2. They were normal in the control group. The BUN and SCr were normal in the two groups. Compared with the control group, the serum ET-1 level in the UC group was significantly higher than that in the control group (P < 0.05). There was no statistical difference in the serum ET-1 level (P > 0.05). There was statistical difference in the serum ET-1 level in the UC group between those with the disease course > or = 5 years and those with the disease course <5 years, showing statistical difference (P < 0.05). There was negative correlation between the serum ET-1 level and FEF25% and between the serum ET-1 level and KCO (P < 0.05). CONCLUSIONS: Serum ET-1 level could reflect the pulmonary injury of UC patients earlier. Serum ET-1 level might be a sensitive indicator reflecting the pulmonary injury of UC. The pulmonary injury of UC patients might be correlated with small airway obstruction, reduced lung elasticity, and injured lung diffusion.

Ginsenoside Re attenuates diabetes-associated cognitive deficits in rats.

OBJECTIVE: This study was designed to investigate the effect of ginsenoside Re (Re) on cognitive functions, oxidative stress and inflammation in streptozotocin-induced diabetic rats. RESEARCH DESIGN AND METHOD: Diabetic rats were treated with Re (40mg/kg) for 8weeks, blood glucose and body weight were measured monthly and weekly, respectively. Cognitive performances were evaluated with Morris water maze. Brain was obtained for measurements of TNF-α and malondialdehyde (MDA) contents in both temporal cortex and hippocampus, blood was collected for assays of TNF-α, MDA and reduced glutathione (GSH) levels. RESULTS: Learning and memory abilities were significantly (both P<0.01) impaired in diabetic rats, accompanied by the marked (all P<0.01) elevations of TNF-α and MDA levels in temporal cortex and hippocampus. Increment of MDA and decrement of GSH in serum also occurred with significant differences (both P<0.01). Chronic treatment with Re markedly (P<0.05) improved the cognition of diabetic rats, evidenced by the decreased escape latency and the increased percentage of time spent in the target quadrant. Furthermore, Re treatment remarkably (P<0.05) reduced the levels of TNF-α and MDA in both brain areas of diabetic rats. Decline of MDA level and elevation of GSH level in serum were also seen in Re-treated diabetic rats, coupled with decrease in serum glucose level, all with statistically significant differences. CONCLUSIONS: Our findings firstly provide the first evidence that ginsenoside Re can remarkably attenuate diabetes-associated cognitive decline, secondly confirm the involvement of oxidative stress and inflammation in the development of cognitive impairment caused by diabetes, finally point toward the potential of ginsenoside Re as an adjuvant therapy to conventional anti-hyperglycemic regimens as well as diabetes-associated cognitive decline.

Total saponins from Rhizoma Anemarrhenae ameliorate diabetes-associated cognitive decline in rats: involvement of amyloid-beta decrease in brain.

ETHNOPHARMACOLOGICAL RELEVANCE: As a well-known Chinese Materia Medica Rhizoma Anemarrhenae has multiple pharmacological activities including antipyretic, anti-inflammatory, anti-diabetic actions, etc. This study was designed to investigate effects of total saponins from Rhizoma Anemarrhenae (TS) on diabetes-associated cognitive decline in rats and influence on amyloid-beta (Aß) levels in brain and inflammation. MATERIALS AND METHODS: Diabetic rats induced by intraperitoneal administration of streptozotocin, were randomized into two groups: diabetes and TS-treated diabetes. Blood glucose and body weight were measured monthly and weekly, respectively. After seven weeks, cognitive performances were evaluated with Morris water maze. Then, brain was obtained for assay of Aß and TNF-α levels, and blood was collected for TNF-α assay. RESULTS: Aß(1-40), Aß(1-42) and TNF-α levels were dramatically (all P<0.01) increased both in temporal cortex and hippocampus of diabetic rats, coupled with impairment of cognition, compared with those of the control. Chronic TS (200mg/kg) treatment markedly (P<0.05) improved the learning ability of diabetic rats, and significantly (all P<0.05) reduced Aß(1-40), Aß(1-42) and TNF-α levels in cortex as well as Aß(1-40) level in hippocampus, whereas showed a decreased tendency for Aß(1-42) and TNF-α levels in hippocampus. Moreover, eight-week treatment with TS remarkably (P<0.05) inhibited the elevation of TNF-α level in serum of diabetic rats, and significantly (both P<0.01) decrease the fasting blood glucose level and increase the body weight of diabectic rats. CONCLUSION: Our findings demonstrate that diabetes-associated cognitive decline is, at least in part, due to brain Aß accumulation in diabetic condition, and efficacy of TS to diabetes-associated cognitive decline in rats is a sum of reduction of Aß accumulation and inflammation in brain as well as attenuation of major symptoms of diabetes.

[Effect of triangle drugs as ginseng, Trichosanthes kirilowii maxim and rhubarb on the level of blood lipids and related pro-inflammatory cytokines during the process of treating atherosclerosis].

OBJECTIVE: To study the effect of triangle drugs as ginseng, Trichosanthes kirilowii Maxim, and rhubarb on the levels of blood lipids as [total cholesterol (TC), triglyeride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)] and pro-inflammatory cytokines as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and high sensitive C reactive protein (hs-CRP) during the process of treating atherosclerosis. METHODS: Twenty New Zealand rabbits were randomly divided into three groups after one-week adaptive feeding, i.e., the normal control group (n=6), the model group (n=6), and the triangle drugs group (n=8). High fat diet was fed to rabbits in the triangle drugs group and the model group at the daily dose of 100 g for six weeks. Iliac artery was injured in the model group and the triangle drugs group at the seventh week using balloon injury. High fat diet was successively fed to those after surgery for six weeks. At the same time of modeling, preventive medication (at the daily dose of dry ginseng 0.64 g/kg, Trichosanthes kirilowii Maxim 2.14 g/kg, and prepared Radix et Rhizoma Rhei with wine 0.43 g/kg, with the volume of 2 mL/kg) was administered by gastrogavage to rabbits in the triangle drugs group. Changes of blood lipids levels and related pro-inflammatory cytokines were dynamically observed. RESULTS: On the 7th week (before surgery), the levels of TC, TG, HDL-C, and LDL-C in the model group, TC, HDL-C, and LDL-C in the triangle drugs group significantly increased, showing significant difference when compared with those of the normal control group (P < 0.05). The levels of pro-inflammatory cytokines in the model group and the triangle drugs group were significantly higher than those in the normal control group (P < 0.05). Levels of TC, TG, and LDL-C were lower in the triangle drugs group than in the model group, showing statistical difference (P < 0.05). After the 8th week the levels of blood lipids and ICAM-1 in the model group, and levels of TC, LDL-C, HDL-C, and ICAM-1 in the triangle drugs group were significantly higher than those of the normal control group, showing statistical difference (P < 0.05). After the 12th week levels of blood lipids in the model group, LDL-C and HDL-C in the triangle drugs group were significantly higher than those of the normal control group, showing statistical difference (P < 0.05). The LDL-C level was lower in the triangle drugs group than in the model group, showing statistical difference (P < 0.05). The levels of VCAM-1, ICAM-1, and hs-CRP in the model group were obviously higher than those in the triangle drugs group and the normal control group, showing statistical significance (P < 0.05). The hs-CRP level was higher in the triangle drugs group than in the normal control group, showing statistical difference (P < 0.05). CONCLUSIONS: The triangle drugs may postpone the process of atherosclerosis by lowering blood lipids levels, especially by lowering the elevating levels of TC and LDL-C. Its roles in decreasing the level of pro-inflammatory cytokines might be associated with lipids lowering and anti-inflammation. Its roles may also be associated with improvement of the endothelial function and inhibition of the smooth muscle proliferation.

In vitro suppression of quercetin on hypertrophy and extracellular matrix accumulation in rat glomerular mesangial cells cultured by high glucose.

Quercetin's protective effects on the glomerulosclerosis of diabetic nephropathy (DN) in rat mesangial cells were investigated. The cell cycles, type IV collagen and laminin, TGF-ß(1) mRNA, Smad 2/3 and Smad 7, and activities of cell antioxidases were measured. Compared with the high glucose group, quercetin may decrease the cell percentages of G(0)/G(1) phase, Smad 2/3 expression, laminin and type IV collagen, and TGF-ß(1) mRNA level significantly. The antioxidant capacity, the cell percentages of S phase and Smad 7 expression was significantly increased by quercetin. These results suggest that quercetin is a protective agent against glomerulosclerosis in DN.

Ginkgo biloba extract prevents glucose-induced accumulation of ECM in rat mesangial cells.

Pathological remodeling characterized by extracellular matrix (ECM) accumulation contributes to diabetic nephropathy (DN). This study evaluated the effects of Ginkgo biloba extract (GbE) on the metabolism of the ECM in rat mesangial cells cultured in hyperglycemic conditions. The cultured mesangial cells in high glucose conditions were allotted into six groups: normal control group, high glucose group, low concentration of GbE group, moderate concentration of GbE group, high concentration of GbE group, and captopril group. In the presence of high glucose, the levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and extracellular matrix metalloproteinase inducer (EMMPRIN) were decreased significantly, and the levels of tissue inhibitor of metalloproteinase-2 (TIMP-2), tissue inhibitor of metalloproteinase-1 (TIMP-1) and plasminogen activator inhibitor-1 (PAI-1) were increased significantly. These changes were reversed by GbE. GbE lowered the levels of transforming growth factor-beta(1) (TGF-beta(1)), insulin-like growth factor-1 (IGF-1) and connective tissue growth factor (CTGF) of the high glucose group. Furthermore, GbE also decreased the expressions of collagen IV and laminin of the high glucose group. In summary, the results suggest that GbE postpones the extracellular matrix accumulation by inhibiting the synthesis of ECM and promoting the degradation of ECM, and therefore, is a potential drug for the prevention and treatment of DN.

Ginkgo biloba extract prevents against apoptosis induced by high glucose in human lens epithelial cells.

AIM: To investigate the protective effects of Ginkgo biloba extract (GBE) on high glucose-induced apoptosis of human lens epithelial cells (HLEC) and the possible molecular mechanisms. METHODS: The cultured HLEC were allotted into 6 groups: normal group, high glucose group, low-, moderate-, and high-dose GBE group, and the bendazac lysine group. Cell viability, cell apoptosis, the activities of cell antioxidases, aldose reductase, caspase-3, the levels of cell antioxidants, and the expressions of Bcl-2 and Bax were assessed by different methods. RESULTS: After being incubated with high glucose for 24 h, HLEC underwent apoptosis and exhibited significant oxidative stress. In the presence of GBE at different doses, the rate of HLEC apoptosis was lower and the oxidative stress state was significantly ameliorated. The increased ratio of Bax to Bcl-2 was significantly reduced and the activation of caspase-3 was suppressed by GBE in a dose-dependent manner. CONCLUSION: GBE prevents HLEC from high glucose-induced apoptosis through inhibiting oxidative stress, reducing the ratio of Bax to Bcl-2, and decreasing the activity of caspase-3. Therefore, GBE has a potential protective effect against diabetic cataract formation.