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Aim: To construct an edaravone-encapsulated liposomes (EDV-LIPs) formulation against acute ischemic stroke. Methods: EDV-LIPs were prepared by the film dispersion method. The biosafety was evaluated both in vitro and in vivo by flow cytometry and the histological staining method. Biodistribution and therapeutic effect of EDV-LIPs against acute ischemic stroke was investigated by fluorescent imaging, the behavior test, laser speckle imaging and triphenyltetrazolium chloride staining. Results: The nanoliposomes had a long circulation time and could accumulate in the brain lesion region in ischemic stroke rats. EDV-LIPs show good biosafety. EDV-LIPs could restore more cerebral blood flow, reduce infarct volume and decrease neuronal apoptosis. Conclusion: EDV-LIPs provide an effective alternative for drug-targeted delivery against acute ischemic stroke.

Exploring the distribution of phosphorus (P) fractionsin soil aggregates is helpful to improve soil P availa-bility during Chinese fir planting. In this study, soil samples were collected in the 0-20 cm soil layer from Chinese fir plantations with different stand ages (9 a, 17 a, and 26 a) and one nearby abandoned land (CK) in Rongshui County, Guangxi, China. Soil aggregates were classified into >2 mm, 1-2 mm, 0.25-1 mm, and <0.25 mm size classes through dry-sieving process, and then soil P fractions in different sized aggregates were measured. These results showed that: 1) The composition of soil aggregates showed significant difference among different stand ages. As the major aggregate fractions in soil, the contents of >2 mm aggregates increased firstly and then decreased over time, and peaked in the 17 a Chinese fir plantation. The changes of soil mean weight diameter (MWD) and geometric mean diameter (GMD) during Chinese fir planting were the same as the content of >2 mm aggregates. 2) Soil total P, inorganic P, and organic P contents did not differ among different sized aggregates. However, soil available P content was mainly distributed in >2 mm aggregates with a range of 1.23-7.33 mg·kg -1 . Compared with CK, soil total P, available P, and inorganic P contents were significantly higher in Chinese fir plantations, and their contents increased firstly and then decreased over time. Soil total P (322.40 mg·kg -1 ) and available P (7.33 mg·kg -1 ) contents were the highest in the 9 a plantations, and soil inorganic P content (114.05 mg·kg -1 ) was the highest in the 17 a plantation. Moreover, soil organic P content showed an order of 9 a > 26 a >17 a > CK, with the highest content (210.00 mg·kg -1 ) in the 9 a plantation. 3) The distribution of P stock in soil aggregates was related to the contents of different sized aggregates, with >2 mm aggregates having the highest P stock. Except for organic P, soil P stock increased firstly and then decreased with the increases of stand age. In conclusion, Chinese fir planting was helpful to improve soil aggregate stability and to promote the increase of soil P level before the stand age of 17 a. However, Chinese fir planting could result in the degradation of soil aggregates and in the decrease of soil P level after 17 a. The formation and stabilization of >2 mm aggregates played an important role in the maintenance of soil quality and soil P supply level after 17 a Chinese fir planting.

Objective: To investigate the protective effects of Zuogui Wan (ZGW) on bone loss induced by ovariectomy (OVX) and its mechanism via orexin-A and orexin receptors in the osteoporosis rat model., Methods: Fifty Sprague-Dawley female rats were randomly divided into sham-operated (sham) group and four OVX subgroups. Rats subjected to sham and OVX were treated with the vehicle (OVX, 1 mL/100 g weight, n = 10), 17β-estradiol (E2, 50 μg*kg-1*d-1), and ZGW at the doses of 2.3 (ZGW-L) and 4.6 (ZGW-H) g/kg/day lyophilized powder daily for 3 months, respectively. The serum biochemical parameters of 17β-estrogen (17β-E2), tartrate-resistant acid phosphatase (TRACP-5b) and bone alkaline phosphatase (BALP) were measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to detect the changes in the morphological structure in bones. Microcomputed tomography was used to evaluate the bone mineral density and microarchitecture of the distal femur. The gene or protein expression of orexin-A, orexin receptor 1 (OX1R), orexin receptor 2 (OX2R), osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were assayed by either quantitative polymerase chain reaction or Western blot analysis., Results: Compared with the OVX group, ZGW could reduce the serum level of TRACP-5b and increased the serum levels of BALP and17β-E2 (P < 0.01). Meanwhile, ZGW could prevent bone loss and improved bone trabecular microarchitecture by increasing the trabeculae structure thickness and trabecular number, and arranging the trabeculae structure properly. Compared with the OVX group, it was upregulated for the orexin-A and OX2R mRNA or protein expression from the hypothalamus and tibiae, and OPG in the tibiae of ZGW groups (P < 0.01, < 0.05), while downregulated for the OX1R mRNA and protein expression in the tibiae and hypothalamus and RANKL from the tibiae (P < 0.01)., Conclusion: ZGW exhibited a protective effect for PMOP that may be mediated via orexin-A and orexin receptors regulation.

Non-alcoholic fatty liver disease (NAFLD) is a complication of childhood obesity and an oxidative stress-related multisystem disease. A mitochondria-targeting hydrogen sulfide (H 2 S) donor AP39 has antioxidant property, while the mechanism underlying the function of AP39 on pediatric NAFLD remains undefined. Here, 3-week-old SD rats were received a high-fat diet (HFD) feeding and injected with AP39 (0.05 or 0.1 mg/kg/day) via the tail vein for up to 7 weeks. AP39 reduced weight gain of HFD rats and improved HFD-caused liver injury, as evidenced by reduced liver index, improved liver pathological damage, decreased NAFLD activity score, as well as low alanine transaminase (ALT) and aspartate transaminase (AST) activities. AP39 also reduced serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) concentrations but increased high-density lipoprotein-cholesterol (HDL-C). Moreover, AP39 prevented reactive oxygen species (ROS) generation, reduced MDA content and increased glutathione (GSH) level and superoxide dismutase (SOD) activity. Furthermore, AP39 increased H 2 S level, protected mitochondrial DNA (mtDNA), reduced mitochondrial swelling, and restored mitochondrial membrane potential (MMP) alteration. Notably, AP39 diminished HIF-1α mRNA and protein level, possibly indicating the alleviation in mitochondrial damage. In short, AP39 protects against HFD-induced liver injury in young rats probably through attenuating lipid accumulation, oxidative stress and mitochondrial dysfunction.

The present study aimed to investigate whether the thyroid-stimulating hormone receptor (TSHR) autoantibodies (Ab) from mothers with Graves' disease (GD) could cause neonatal thyroid disease and the underlying mechanisms of this. An adenovirus expressing the TSHR A-subunit and a control adenovirus expressing β-galactosidase was constructed by Beijing Sino Geno Max Co., Ltd. The sequences were subsequently verified and amplified via PCR. A GD model was established in female BALB/c mice (n=90) by three intramuscular injections of a TSHR-expressing adenovirus (Ad-TSHR). Mice injected with Ad-β-galactosidase served as a sham immunization group. The immunized females were paired with unimmunized males to generate offspring. The serum levels of TSHR-Ab and thyroxine (T4) of mothers and neonates were measured after delivery. Breast milk was collected from the stomachs of neonatal mice to determine the TSHR-Ab levels. The positive rate of serum TSHR-Ab (>0.3 IU/l) in the TSHR group was 99% (89/90) and 0% in the sham group. The mother mice in the TSHR group had elevated serum T4 levels and the thyroid pathological features of Graves' hyperthyroidism.GD mice gave birth to smaller newborns with thyroid pathological changes and higher serum levels of TSHR-Ab and T4, compared to the offspring in the sham group. The TSHR-Ab levels in breast milk from the GD mice declined with time. Mice immunized with Ad-TSHR exhibited the clinicopathological features of human GD and give birth to neonates with thyroid disease at birth., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Yu et al.)

Montelukast is a leukotriene receptor antagonist that is known to prevent allergic rhinitis and asthma. Blocking the Cysteinyl leukotriene receptor (CysLTR1), one of the primary receptors of leukotrienes, has been demonstrated to be efficacious in ameliorating experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), through disrupting chemotaxis of infiltrating T cells. However, the role of CysLTR1 in the pathogenesis of MS is not well understood. Here, we show that MS patients had higher expression of CysLTR1 in the circulation and central nervous system (CNS). The majority of CD4 + T cells expressed CysLTR1 in MS lesions. Among T-cell subsets, Th17 cells had the highest expression of CysLTR1, and blocking CysLTR1 signalling abrogated their development in vitro. Inhibition of CysLTR1 by montelukast suppressed EAE development in both a prophylactic and therapeutic manner and inhibited myelin loss in EAE mice. Similarly, the in vivo results showed that montelukast inhibited Th17 response in EAE mice and that Th17 cells treated with montelukast had reduced encephalitogenic in adoptive EAE. Our findings strongly suggest that targeting Th17 response by inhibiting CysLTR1 signalling could be a promising therapeutic strategy for the treatment of MS and CNS inflammatory diseases., (© 2021 John Wiley & Sons Ltd.)

Gasdermin D (GSDMD) plays a causal role in NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis eruption, which has been regarded as a potential therapeutic target for pyroptosis-related diseases including acute gouty arthritis. In the present study, the synthesized PEI-Chol (cholesterol grafted polyethylenimine) was assembled with GSDMD small interfering RNA (siRNA) to form PEI-Chol/siGSDMD polyplexes, which provided high transfection efficiency for siRNA-mediated GSDMD knockdown. Then we evaluated the effect of GSDMD siRNA-loaded PEI-Chol on inflammatory cascades in bone-marrow-derived macrophages (BMDMs) and acute gouty arthritis animal models under MSU exposure. When accompanied by pyroptosis blockade and decreased release of interleukin-1 beta (IL-1β), NLRP3 inflammasome activation was also suppressed by GSDMD knockdown in vivo and in vitro . Moreover, in MSU-induced acute gouty arthritis mice, blocking GSDMD with siRNA significantly improved ankle swelling and inflammatory infiltration observed in histopathological analysis. Furthermore, investigation using a mouse air pouch model verified the effect of siGSDMD-loaded PEI-Chol on pyroptosis of recruited macrophages and related signaling pathways in response to MSU. These novel findings exhibited that GSDMD knockdown relieved acute gouty arthritis through inhibiting pyroptosis, providing a possible therapeutic approach for MSU-induced acute gouty arthritis molecular therapy using PEI-Chol as a nucleic acid delivery carrier.

Exploring the microscopic characterization of organic carbon and nutrients in surface soil of different Chinese fir stands at aggregate scale can lay a theoretical foundation for promoting the sustainable use of soil resources with implications for improving soil health and fertility. We mea-sured the concentrations of soil organic C (OC), total nitrogen (TN), alkali-hydrolyzed nitrogen (AN), Olsen-P (AP), and available K (AK) in aggregate fractions collected from 0-10 cm and 10-20 cm soil layers in three different stands, mixed plantation of Cunninghamia lanceolata and Michelia macclurei (Ⅰ), C. lanceolata and Mytilaria laosensis (Ⅱ) and pure plantation of C. lanceolata (Ⅲ) respectively. Soil aggregates were classified into >2, 0.25-2, and <0.25 mm fractions by a dry-sieving procedure. The organic carbon and nutrient contents of soil aggregates in different stands increased with the decreases of particle size while the contribution rate of aggregates with different particle sizes to soil organic carbon and nutrient storage in 0-10 cm soil layer mainly was (>2 mm)>(0.25-2 mm)>(<0.25 mm), which was (>2 mm)>(<0.25 mm)>(0.25-2 mm) in 10-20 cm soil layer. The average weight diameter (MWD), the contents and stocks of OC, TN, AN and AP in surface soil aggregates of different stands ranked as Ⅰ>Ⅱ>Ⅲ (except the AP in 10-20 cm soil layer), while the contents and stocks of AK ranked as Ⅲ>Ⅰ>Ⅱ. Compared with pure plantation, aggregate structure of surface soil of mixed plantations was more stable, and Ⅰ was better than Ⅱ, because Ⅰ was artificially disturbed but Ⅱwas not. Therefore, the mixed plantation of C. lanceolata and M. macclurei could effectively promote the formation and stability of soil aggregates, and alleviate decomposition of soil organic matter and nutrient loss in plantations.

Understanding the response mechanism of soil aggregate-associated organic carbon (OC) and nutrients to tea cultivation age can lay a theoretical foundation for improving soil fertility, ensuring soil health, and promoting sustainable utilization of soil resources in the tea plantations. In this study, concentrations of soil OC and nutrient were analyzed in >2, 2-1, 1-0.25, and <0.25 mm fractions (split by a dry-sieving procedure) at the 0-20 cm soil layer in four tea plantations with Baimao tea of different ages (8, 17, 25, and 43 a) in southern Guangxi, China. The distribution of soil aggregates showed that the dominant aggregates were >2 mm fractions with a mean value of 63.8%, followed by <0.25 mm fractions, while 2-1 and 1-0.25 mm fractions with mean values of 9.9% and 7.8%, respectively. As an indicator of soil aggregate stability, the mean weight diameter (MWD) in the tea plantations showed an order of 17 a >8 a >25 a >43 a. Regardless of tea cultivation age, soil aggregate-associated OC and total nitrogen (TN) concentrations increased with increasing aggregate size. Soil OC and TN concentrations in >2 and 2-1 mm fractions were significantly higher than those in other fractions. The mean values of soil OC and TN concentrations were 18.76 and 0.84 g·kg -1 in the >2 mm fractions, and were 18.65 and 0.80 g·kg -1 in the 2-1 mm fraction. Soil aggregate-associated available nitrogen (AN), available phosphorus (AP), and availa-ble potassium (AK) concentrations were highest in the <0.25 mm fractions with mean values of 50.43, 23.06, and 68.04 mg·kg -1 , respectively. Long-term tea cultivation was favorable to the accumulation of soil OC, TN, AN, and AP, whereas the accumulation rates of these element stocks in the whole soil decreased with increasing tea cultivation age. In contrast, soil AK was susceptible to leaching in tea cultivation, with the loss rate of this element stock in the middle stage (from 17 to 25 a) being higher than those in the other stages. To ensure soil quality and promote the sustainable utilization of soil resources, more attention should be paid to the problems such as the decrease of soil aggregate stability and the aggravation of AK loss after 17 a of tea cultivation.

Purpose: To describe our experience using microsurgically fabricated, multilobed, chimeric, lateral arm (LA) flaps to reconstruct hand injuries with complex, multidigit, soft tissue defects and to evaluate the morbidity and esthetic and functional outcomes of the donor sites., Methods: We performed a single center, retrospective analysis of 21 patients with hand wounds treated from October 2013 to February 2016. All patients underwent reconstruction using multilobed, chimeric, free, LA flaps. A self-reported questionnaire was used to assess donor site morbidity and satisfaction with the esthetic and overall functional result. Outcome measures were the Disabilities of the Arm, Shoulder and Hand (DASH) score, static 2-point discrimination score, and visual analogue scale., Results: The study included 21 patients (20 males and 1 female), with an average age of 32.14 years (range 18-45 years), who sustained traumatic injuries in road traffic accidents (n = 2) or industrial devices (n = 19). The average DASH score was 28.25 ± 2.3, the average 2-PD score was 7.20 ± 1.30, and the average visual analogue scale (VAS) was 0.38 ± 0.40. All 21 patients had sensory disorders at the donor site. Postoperative donor site complications comprised wound dehiscence (n = 1) and hematoma (n = 3). The patient-rated satisfaction score for the donor site was 5.40 ± 0.90, and 70% of the patients would undergo the same surgery again., Conclusion: Microsurgical fabrication of multilobed, chimeric, LA flaps can exhibit sensory recovery and minimal pain but may cause hematoma and sensory disorders at the donor site. The flaps are a viable alternative for the reconstruction of complex, multidigit, soft tissue defects of the hands., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To synthesize and select an estrogen receptors aptamer that can be used in immunostaining of breast cancer tissues., Methods: ER protein was purified. ER aptamer that showed a high affinity and specificity for ER was synthesized and selected and by SELEX. Ligand -receptor interactions assay was adopted to measure the affinity of the aptamer-ER complex. Both the biotinylated aptamer and the anti-ER monoclonal antibody were tested for immunohistochemical staining of ER status on 105 breast cancer samples. Agreement on the detection of ER expression was determined by Kappa statistics., Results: The dissociation contant (Kd) of the biotinylated aptamer-ER complex, as calculated by a linear regression analysis, was determined to be (0.34±0.05) nmol/L ( n =3, r =0.989). The binding capacity (B max ) was 769.23 fmol/(mg prot·nmol -1 ·L -1 ). The ER aptamer and the anti-ER antibody both exhibited identical specificity to ER-expressing breast cancer cells. There was a high agreement between the two methods ( n =105, Kappa value=0.943, 95% confident interval=0.879-1.006, P <0.05 for the ER positive and negtive samples; n =75, Kappa value=0.805, 95% confident interval=0.642-0.967, P <0.05 for the ER weak and moderate/strong expression samples). Both the anti-ER antibody and the ER aptamer can also recognized breast cancer cells at the same sites. There was no expression in the negative controls. There were also positive expressions in the 2 endometrial cancer tissues by using biotinylated aptamer., Conclusions: Our results indicated that the synthesized ER aptamer has a high affinity to bind ER. ER aptamer and the anti-ER antibody can both be used for immunohistochemical staining of ER status in breast cancer tissue., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Techniques using the anteromedial portal (AMP) and accessory anteromedial portal (AAMP) are commonly used in anterior cruciate ligament (ACL) reconstruction. The aim of this study was to investigate the radiological and clinical outcomes of arthroscopic single-bundle ACL reconstruction using the AMP or AAMP technique to drill the femoral tunnel. The records of 157 patients who underwent single-bundle ACL reconstruction using the AMP or AAMP technique between 2011 and 2015 were reviewed. The femoral tunnel clock-face position and femoral tunnel and tibial tunnel anterior-posterior (AP) inclination angles were assessed on axial or AP magnetic resonance images. At last follow-up, the Lachman test and pivot-shift test were used to evaluate AP and rotational stability, respectively. The Lysholm knee scoring scale and the International Knee Documentation Committee (IKDC) form were used to evaluate clinical and functional results. No statistically significant differences were found between the groups in patient age, sex, follow-up period, or affected side distribution. The mean femoral tunnel inclination angle was 31.13 ± 8.06 degrees in the AMP group and 30.17 ± 9.02 degrees in the AAMP group ( p  = 0.513). The tibial tunnel inclination angle in the AMP group (16.28 ± 7.89 degrees) was not different from that in the AAMP group (13.70 ± 6.08 degrees). No significant differences were observed between the two groups in the Lachman test, pivot-shift test, Lysholm knee scoring scale, or IKDC scores. The AAMP technique was not clinically superior to the AMP technique in ACL reconstruction. This is a retrospective comparative study and its level of evidence is III., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To explore efficacy and safety of simulated artificial pancreas in modulating stress hyperglycemia in critically ill patients., Methods: A prospective randomized controlled study was performed. Seventy-two critically ill patients with stress hyperglycemia, aged 18-85 years, acute physiology and chronic health evaluation II (APACHE II) score over 15, two consecutive random blood glucose 11.1 mmol/L or higher, glycated hemoglobin (HbA 1C ) below 0.065, unable to eat food for 3 days after inclusion, or only accepting parenteral nutrition, admitted to intensive care unit (ICU) in Shanghai Punan Hospital of Pudong New District from January 1st, 2015 to June 30th, 2017 were enrolled. The patients were divided into three groups according to the random number table method, high-intensity group and low-intensity group were injected Novolin R (high-intensity group 2/3 dosage, low-intensity group 1/3 dosage) to modulate stress hyperglycemia by simulated artificial pancreas. Simulated artificial pancreas consisted of Guardian real time glucose monitoring system (GRT system), close-circle control algorithm and micro-pump; subcutaneous injection of Humulin 70/30 was applied to modulate stress hyperglycemia in humulin group. Real-time glucose levels of interstitial fluid in abdominal wall, equivalent to blood glucose levels, 10 minutes each time, were monitored by using of GRT system for all patients in three groups. Fasting serum levels of stress hormones including epinephrine and cortisol and insulin resistance index (IRI) were recorded within 24 hours after inclusion. Mean blood glucose, blood glucose variation coefficient, blood glucose target-reaching rate, blood glucose target-reaching time, hypoglycemia rate and 6-month mortality were measured. Twenty healthy adults from health administration department of the hospital were recruited as healthy control group., Results: A total of 60 eligible critically ill patients were included in this study, each group with 20 patients. There was no significant difference in gender, age, APACHE II scores among three groups. The levels of serum epinephrine, cortisol and IRI within 24 hours after inclusion in the three groups were significantly higher than those in healthy control group. The mean blood glucose levels of humulin group, low-intensity group, high-intensity group were decreased (mmol/L: 10.2±3.2, 8.4±2.6, 8.1±2.2), the blood glucose target-reaching rate were increased [40.2% (3 295/8 196), 71.1% (5 393/7 585), 80.4% (6 286/7 818)], the blood glucose target-reaching time were shortened (hours: 49.1±5.8, 24.6±4.6, 17.5±4.2), the hypoglycemia rates were increased respectively [1.3% (108/8 196), 2.8% (211/7 585), 4.0% (313/7 818)], with statistically significant differences (all P = 0.000). There was no significant difference in blood glucose variation coefficient and 6-month mortality among three groups [blood glucose variation coefficient: (29.4±3.7)%, (28.5±5.3)%, (26.1±4.6)%, 6-month mortality: 55.0%, 45.0%, 40.0%, all P > 0.05]., Conclusions: Simulated artificial pancreas could effectively and safely modulate stress hyperglycemia in critically ill patients, high-intensity modulation could bring about better efficacy in the regulation of hyperglycemia. High-frequency blood glucose monitoring by using GRT system could promptly identify hypoglycemia and help it to be corrected.

Purpose: Lymphatic vessels are mainly regarded as passive conduits for the dissemination of cancer cells. In this study, we investigate whether and how the tumor-associated lymphatic vessels may play an active role in tumor metastasis., Experimental Design: In situ laser capture microdissection of lymphatic vessels followed by cDNA microarray analysis was used to determine the expression profiling of lymphatic endothelial cells (LEC). Gene expression levels and activity of signaling pathways were measured by real-time RT-PCR, ELISA, or immunoblotting. Lymphangiogenesis was assessed by IHC. Lymph node metastasis was measured using fluorescence imaging. The effects of SEMA4C on lymphangiogenesis in vitro were evaluated using migration assay and tube-formation assay of LECs., Results: Tumor-associated LECs are molecularly and functionally different from their normal counterparts. In addition to expressing high levels of membrane-bound SEMA4C, tumor-associated LECs also produced soluble SEMA4C (sSEMA4C). Increased serum sSEMA4C was detected in patients with breast cancer and cervical cancer. Patients with metastasis had much higher levels of serum sSEMA4C. sSEMA4C promoted lymphangiogenesis by activating PlexinB2-ERBB2 signaling in LECs, and promoted the proliferation and migration of tumor cells by activating PlexinB2-MET signaling, thus promoting lymphatic metastasis. Although the SEMA4C signaling pathways differ between LECs and tumor cells, RHOA activation was necessary for the effects of SEMA4C in both types of cells., Conclusions: Tumor-associated LECs produce sSEMA4C to promote lymphatic metastasis of tumors. Our results suggest that SEMA4C and RHOA might be potential therapeutic targets, and that higher serum sSEMA4C could be a marker for breast cancer and cervical cancer. Clin Cancer Res; 23(1); 214-24. ©2016 AACR., (©2016 American Association for Cancer Research.)

Objective: To study the chemical constituents from ethyl acetate extract of Psidium guajava leaves., Methods: The constituents were separated and purified by silica gel and Sephadex LH-20 column chromatography and their structures were identified on the basis of physicochemical properties and spectral data., Results: Eleven compounds were isolated and identified as 6,10,14-trimethyl-2-pentadecanone (1), phytyl-acetate (2), cubenol (3), eucalyptin (4), n-docosanoic acid-p-hydroxy-phenethylol ester (5),8-methyl-5,7- dihydroxy-flavonone (6), 6-methyl-5,7-dihydroxy-flavonone (7), betulinic acid (8), carnosol (9), quercetin (10), and 2,4,6-tirhydroxy- 3,5-dimethyl-diphenylketone-4-O-(6'"-O-galloyl)-β-D-glucoside (11)., Conclusion: Compounds 1-9 are isolated from this plant for the first time.

Background: Allostatic load (AL) measures overall physiological wear and tear on one's body, as a preclinical marker of pathophysiologic processes that precede the onset of disease. We studied the association of dietary habits with AL., Methods: Consecutive patients visiting a tertiary hospital Health Promotion Center from September 2009 to February 2010, older than 20 years with metabolic syndrome were selected for study (n = 204). By multivariable linear regression analysis, we investigated the association of various dietary habits evaluated by questionnaires., Results: In male, multivariable linear regression showed a significant negative association between fat preference and AL with BMI ≥ 30 (1st quartile [Q] vs. 2Q: β = -3.71; 95% confidence interval [CI], -6.26 to -1.16), a significant negative association between salt preference and AL with BMI 25-30 (β = -1.36; 95% CI, -2.46 to -0.26), a negative association between appetite control and AL with BMI < 25 (1Q vs. 3Q: β = -1.54; 95% CI, -3.00 to -0.096), a significant positive association between appetite control and AL with BMI 25-30 (1Q vs. 3Q: β = 1.30; 95% CI, 0.12 to 2.48), and a significant positive association between eating in response to food cues and AL in males with BMI 25-30 (1Q vs. 4Q: β = 1.09; 95% CI, 0.020 to 2.15)., Conclusion: Our results suggest that metabolic syndrome patients should be discouraged from eating fat and eating in response to food cues, and should be educated about nutrition and balanced diet.

Atrial fibrillation (AF) has been considered as a growing epidemiological problem in the world, with a substantial impact on morbidity and mortality. Ambulatory electrocardiography (e.g., Holter) monitoring is commonly used for AF diagnosis and therapy and the automated detection of AF is of great significance due to the vast amount of information provided. This study presents a combined method to achieve high accuracy in AF detection. Firstly, we detected the suspected transitions between AF and sinus rhythm using the delta RR interval distribution difference curve, which were then classified by a combination analysis of P wave and RR interval. The MIT-BIH AF database was used for algorithm validation and a high sensitivity and a high specificity (98.2% and 97.5%, respectively) were achieved. Further, we developed a dataset of 24-h paroxysmal AF Holter recordings (n=45) to evaluate the performance in clinical practice, which yielded satisfactory accuracy (sensitivity=96.3%, specificity=96.8%).

Objective: To explore the expression and clinical significance of signal protein Sema4C in esophageal cancer, gastric cancer and rectal cancer., Methods: Fifty esophageal cancer, 75 gastric cancer, 50 rectal cancer and 20 corresponding normal mucous membrane specimens, collected during the period of January 2008 to December 2010, were detected with streptavidin-peroxidase immunohistochemistry to detect the expression levels of Sema4C. And the relationships of the Sema4C expression with clinicopathological data was analyzed., Results: The expression levels of Sema4C in three kinds of cancers were significantly higher than the corresponding normal mucous membranes (80.0% (n = 40) vs 20.0% (n = 4), 77.3% (n = 58) vs 25.0% (n = 5), 80.0% (n = 40) vs 15.0% (n = 3), all P = 0.000). Furthermore, the percentage of Sema4C positive cells was significantly higher in carcinoma nests of tumors with lymphatic metastasis than those without (90.3% (n = 28) vs 63.2% (n = 12), 85.0% (n = 51) vs 46.7% (n = 7), 92.0% (n = 23) vs 68.0% (n = 17), P = 0.049, 0.005, 0.034). However, no significant correlations were found between the Sema4C expression with gender, age, location of tumors, types of cancer cells, cell differentiation, tumor size, depth of invasion or tumor stage (all P > 0.05)., Conclusion: There is a high expression of Sema4C in esophageal cancer, gastric cancer and rectal cancer. And it is strongly correlated with lymphatic metastasis. Thus Sema4C may play critical roles in the invasion and lymphatic metastasis of esophageal cancer, gastric cancer and rectal cancer.

Objective: To investigate clinical outcome of surgical treatment for spinal metastatic tumors., Methods: Thirty-six patients with metastatic spine tumors treated surgically were retrospectivly reviewed from September 2005 to August 2010. There were 15 males and 21 females with an average age of 58 years old (ranged, 27 to 79 years). The site of origin of primary cancer included the breast, prostate, colon, lung, liver, esophagus, kidney, carcinoma, bladder, and 10 patients were with unidentified primary cancer. Five lesions were located in the cervical spine, 17 in the thoracic spine, 13 in the lumbar spine and 1 in the sacral vertebrae. Preoperative evaluation was conducted according to Tokuhashi system: total score 0 to 8 in 9 cases, 9 to 11 in 25 cases, 12 to 15 in 2 cases. The surgical procedures, including PVP, tumor resection and decompression, titanium nets implant, artificial vertebra replacement, bone cement stuffiness and inter fixation, were performed based on Tokuhashi score, location of lesions and neurological symptoms., Results: All the patients were followed up, and the during ranged from 2 months to 60 months with a mean time of 10.8 months. Pain relief was obtained in all patients after operation, and the VAS pain scores declined after operation. Among 14 patients suffering from spinal cord and nerve compromise, 12 patients improved 1 to 2 grades after surgery according to the Frankel grading system. According to the system of the ECOG performance status: 28 patients improved 1 to 2 grades in performance status after surgery. The postoperative survival rates at 3 months, 6 months, 1 year and 2 years were 97.2%, 63.9%, 38.9% and 16.7% respectively. Six patines had bone cement leakage after PVP, and none resulted in severe complications., Conclusion: According to single or multiple spinal metastases, neurological symptoms, spinal stability and patients' condition, the different surgical treatments can be selected for spinal metastatic patients, which can relieve pain, maintain or improve the neurological status, improve quality of life, improve survival rate of patients.

With the increasing complexity of analytical data, traditional data processing methods for spectral analysis can not meet the analysis needs. The chemometrics uses methods of mathematics, statistics and computer sciences to design optimum chemical measurement procedures and to provide maximum information about fluorescence spectrum by analyzing data. In the present paper, the main kinds of three-dimensional fluorescence spectrum, which are widely analyzed by chemometric methods, were illustrated at first. Secondly, an overview of the chemometric methods such as statistical methods, pattern recognition, neural network and the second-order calibration methods is presented. And the applications of these methods are followed by. Finally,the prospect of chemometric methods applied in multidimensional spectral analysis is discussed.

Objective: To explore the pharmacological mechanism of Realgar by the way of studying the effects of Realgar and the prescription containing Realgar named Niuhuang Jiedu Tablet on stress response proteins (heat shock protein 70, HSP70 and heme oxygenase-1, HO-1), inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha), activities of nitric oxide synthetase (NOS) and its isoenzyme (inducible nitric oxide synthetase, iNOS), and complements C3, CA under pathologic status (fever model)., Methods: SD rats were randomly divided into four groups, 15 rats in each: untreated normal group, fever model group, Realgar (90 mg/kg) group and Niuhuang Jiedu Tablet (NJT, 1.404 g/kg) group. Each group was divided into three subgroups (5 rats/subgroup). Blood samples of the rats in subgroups were collected at 1 h, 2 h and 4 h after administration, respectively. ELISA method was used to determine HSP70, IL-1beta, IL-6, and TNF-alpha levels in serum. Dual wavelength spectrophotometry was used to determine activity of HO-1 in serum. Spectrophotometry was used to test activities of nitric oxide synthetase (NOS) and its isoenzyme (inducible nitric oxide synthetase, iNOS) in serum. Immunonephelometery method was used to test complements C3, C4 in serum., Results: Realgar and NJT significantly increased the level of HSP70 in rat serum as compared with the fever model group. Realgar and NJT significantly enhanced the activity of HO-1 in rat serum as compared with the fever model group. The increase ranges of HO-1 activities at different time post administration changed with the arsenic concentration in rat serum. Realgar and NJT significantly decreased the level of IL-1beta in rat serum as compared with fever model group, and the level of IL-lbeta recovered normaly at 4 h after administration. NJT significantly inhibited activities of NOS and iNOS in rat serum as compared with the fever model group at 2 h after administration., Conclusion: Realgar as contained in certain prescriptions, at certain specific levels, assists in removal of internal toxins by inducing stress protein (HSP70, HO-1) to improve the positive stress level in the body and inhibiting some over-releasing inflammatory mediators (IL-1beta) to reduce the inflammatory reactions under pathologic status.

Aim. To study the pharmacokinetics of dihydroartemisinin (DHA) in Artekin (compound dihydroartemisinin) tablets in Chinese healthy volunteers. Methods. Eighteen healthy volunteers (9 males, 9 females) received Artekin tablets for oral administration. The plasma samples of DHA were analysed by liquid-liquid extraction and determined by HPLC/ESI/MS. Results. The plasma DHA concentration-time curves of single dose and repeated doses of DHA were fitted to a two-compartment open model. The mean pharmacokinetic parameters of DHA in a single dose were: t(1/2(beta))=1.245 +/- 0.495 h, C(max)=243.6 +/- 56.15 microg/l, AUC(0 --> infinity)=450 +/- 69 h x microg/l, V(d)=5.75 +/- 2.2 l/kg and Cl=3.245 +/- 0.38 l/h/kg, while in repeated doses they were: t(1/2(beta))=1.085 +/- 0.298 h, AUC(0 --> infinity)=444.35 +/- 80.43 h x ng/ml, V(d)=4.62 +/- 1.128 ml/kg, Cl=3.0125 +/- 0.875 ml/h/kg, respectively. Conclusion. The study showed that DHA in Artekin was rapidly absorbed, distributed and eliminated in the healthy subjects. The pharmacokinetic properties of DHA in Artekin were not affected by gender in a single dose. While in repeated doses accumulation of DHA did not appear after repeated doses.

Objective: To assess the mechanism of exacerbation of colonic damage in rat colitis model induced by trinitrobenzene sulfonic acid (TNBS) treated with celecoxib (a selective COX-2 inhibitor)., Methods: The rats were randomized into four groups. Group 1 and Group 2 were study groups. Group 3 and Group 4 were control groups. Colitis was induced by intracolonic administration of TNBS (25 g/L) in a vehicle of 50% ethanol (0.25 mL) of study groups. The rats of study groups were treated orally, beginning 3 h before induction of colitis and continuing twice per day thereafter for up to 7 d, with celecoxib (1.25 mg/kg, Group 1) and distilled water (1 mL/0.3 kg, Group 2) respectively. In control experiments, the rats of Group 4 were treated orally with celecoxib (1.25 mg/kg) twice per day for up to 7 d. Group 3 rats were healthy control rats. All the rats that survived until the end of the experiment (d 7) were killed and the severity of colonic inflammation was assessed. The COX-2 protein expression in colon tissues was examined by immunohistochemistry., Results: The colonic damage of Group 1 was exacerbated as compared with Group 2. The inflammatory index of colon tissues of Group 1 (8.5+/-2.5) was significantly reduced, as compared with Group 2 (13.5+/-1.9, P<0.05). The levels of COX-2 protein expression was decreased significantly in Group 1 (3.7 x 10(-2)+/-9.5 x 10(-3)) as compared with Group 2 (11.4 x 10(-2)+/-3.8 x 10(-2), P<0.05). The positive rate of COX-2 expression in neural cells of the myenteric plexus in Group 1 (30%) was decreased as compared with Group 2 (90%, P<0.05). No difference was found in the inflammatory index, the levels of COX-2 protein expression and the positive rate of COX-2 expression in neural cells of the myenteric plexus of Group 3 and Group 4., Conclusion: Selective COX-2 inhibitor-celecoxib could decrease the expression of COX-2 in intestinal tissue, attenuate the inflammatory index of colon tissues of experimental colitis induced by TNBS. But the application of celecoxib resulted in exacerbation of colonic damage. These adverse events are probably relevant to the suppression of COX-2 expression in the neural cells of the myenteric plexus, leading to decrease of intestinal contractivity and peristalsis, enteroparalysis, megacolon and death of the rat.

This paper proposes a nonlinear method of detecting the blood oxygen saturation (SpO2) in a wide range on the basis of spectrophotometry, solves the nonlinear problem in detecting SpO2 in a wide range, and improves the applicable range and detection precision. CAN bus communication and DSP fast digital signal processing are utilized in the design of a non-invasive pulse blood oxygen saturation (SpO2) monitor in a wide range, which has a measure error below 3% within a range of 35% approximately 100%, and is applicable for clinical monitoring and detection of cosmonauts' physiological signals. This oximeter's components and their functions are also introduced in detail in the paper.

Objective: To study pharmacokinetics of debydroandrographolide, that is a main active component in Chuanxinlian tablet, in healthy Chinese volunteers., Methods: Eight volunteers were chosen for a single dose of two Chuanxinlian tablet drug concentrations in plasma were measured by HPLC-MS method and the pharmacokinetic parameters were calculated by PK Solution 2.0 software., Results: t(1/2) ka, t(1/2) alpha, t/(1/2) beta, Cmax, tmax and AUCO-t were (0.51 +/- 0.28) h, (0.60 +/- 0.33) h, (3.62 +/- 1.16) h, (147.30 +/- 53.29) microg x L(-1), (1.50 +/- 0.21) h, and (256.63 +/- 64.18) microg x h x L(-1), respectively., Conclusion: Dehydroandrographolide has rapid absorption and long elimination rate after oral administration. The results can provide an evidence for the safety and efficiency of Chuanxinlian tablet in clinical application.

An automatic system for marine meiobenthos separation was developed by using laser-induced fluorescence technology. Rose Bengal was used as organism dye and the spectrums of Rose Bengal were measured. Laser-induced fluorescence system was established to detect marine meiobenthos in sediments. Data obtained from experiments were analyzed by using a mathematical model. The results showed that laser-induced fluorescence technology worked well in the system. The system could select the meiobenthos efficiently and precisely.

Objective: To investigate the effect of the acid inhibitor-Lansoprazole on the distribution of Helicobacter pylori (H.pylori) in stomach., Methods: Biopsy specimens were taken from the duodenal ulcer patients who underwent gastroscopy before and after the treatment of Lansoprazole. The biopsy specimens were taken from the lesser curvature of the antrum and the greater curvature of the corpus respectively. H&E and Warthin-Starry staining were used for detecting the changing of active gastritis and the positive rate of H.pylori., Results: (1)The positive rates of H.pylori before treatment, 4 weeks after treatment and 3 months after treatment, in the lesser curvature of the antrum were 93.02%, 58.14%, and 86.05%, respectively. The positive rate and density of H.pylori 4 weeks after treatment were greatly decreased compared with those before treatment (P<0.001) and also lower than those 3 months after treatment (P<0.05). (2) The positive rate of H.pylori before treatment, 4 weeks after treatment and 3 months after treatment in greater curvature had differences without statistical significance. However, the density of H.pylori 4 weeks after treatment was increased compared with that before treatment., Conclusion: Lansoprazole can change the colonization site of H.pylori in the stomach, decrease the positive rate and the density of H.pylori in lesser curvature of the antrum, but increase the density of H.pylori in the greater curvature of the corpus. This effect is most obvious in one month after treatment. Active gastritis is related to H.pylori.

The distribution of calbindin, calretinin and parvalbumin during the development of the mouse main olfactory bulb (MOB) was studied using immunohistochemistry techniques. The results are as follows: (1) calbindin-immunoreactive profiles were mainly located in the glomerular layer, and few large calbindin-immunoreactive cells were found in the subependymal layer of postnatal day 10 (P10) to postnatal day 40 (P40) mice; (2) no calbindin was detected in the mitral cell layer at any stage; (3) calretinin-immunoreactive profiles were present in all layers of the main olfactory bulb at all stages, especially in the olfactory nerve layer, glomerular layer and granule cell layer; (4) parvalbumin-immunoreactive profiles were mainly located in the external plexiform layer (except for P10 mice); (5) weakly stained parvalbumin-immunoreactive profiles were present in the glomerular layer at all stages; and (6) no parvalbumin was detected in the mitral cell layer at any stage.

Objective: To investigate the intestinal motor function (distal colonic manometry and gastrointestinal transit time) after T. spiralis infection in rats., Methods: Sprague-Dawley rats were infected by administering T. spiralis larvae. Rats were studied on 14, 42, and 56 days post-infection (PI). Age matched non-infected animals served as controls. All rats underwent colonic manometry and gastrointestinal transit time test., Results: (1) The small intestinal inflammation became the most severe on day 14 PI, and returned to normal on day 56. (2) The distal colonic manometry showed significantly active motility in acute infected rats either at rest or upon balloon stimulating. (3) Rat colonic motility parameters were not different from those of the control rats either at rest or upon small volume (1mL) balloon stimulating on day 42 and day 56 PI. But when the balloon was inflated with 2 mL of air, the colonic activity increased significantly compared with that of the control. (4) Gastrointestinal transit time was slower in acute and PI rats than that in the control group., Conclusion: Intestinal motility function was abnormal persistently after transient intestinal nematode infection in rats either in distal colonic manometry or in gastrointestinal transit time.

Objective: To reveal the difference of autofluorescence spectrums of gastric juice derived from malignancy and benignancy for screening and diagnosis of gastric carcinoma., Method: Gastric juice from 202 patients with different gastric diseases were collected, then detected their autofluorescence spectrums (the excitation wavelength is 288 nm, whereas the range of emission wavelength is 300 - 800 nm) after diluted by 1:10. The diagnostic model for gastric cancer was made by Classification and Regression Trees V2.0 software., Results: There were three peaks (the emission wavelength were 320 - 360 nm, 576 nm and 670 - 690 nm respectively) in the autofluorescence spectrums of all patients, though the intensity of the first peak (with the emission wavelength of 320 - 360 nm) were enhanced distinctively in malignance than those in benignancy. The diagnostic model's sensitivity and specificity of prior probability were 91.4% and 83.2% respectively, whereas the sensitivity and specificity of posterior probability were 85.7% and 82.6%., Conclusion: Detection of autofluorescence spectrum of gastric juice has great prospect in the diagnosis and screening gastric carcinoma.

An adjustable folding mount is presented in this paper. It is a multi-functional device for one or more patient's infusions, continuous traction and functional training, and life nursing etc.

The flower of Trollius chinensis Bunge is used for treating upper respiratory infections, pharyngitis, tonsillitis, and bronchitis in Chinese folk medicine. The antiviral activities of the crude extract, total flavonoids, orientin, vitexin and proglobeflowery acid isolated from the flowers of T. chinensis against parainfluenza type 3 (Para 3) virus were investigated. The results showed that the crude extract and total flavonoids exhibited a weak antiviral activity against Para 3. Orientin and vitexin demonstrated potent or moderate antiviral activity against Para 3. Proglobeflowery acid showed weak antiviral activity against Para 3.

Interleukin-6 (IL-6) is increased in brain of aged mice. The purpose of this study was to determine if binding of nuclear factor kappaB (NFkappaB) to the IL-6 promoter is responsible for the age-related increase in brain IL-6. In an initial study, the effect of age on IL-6 in brain was verified as IL-6 protein was increased in brain of aged mice compared to adult and juvenile mice. Competitive RT-PCR showed that IL-6 mRNA concentration was at least 4-fold higher in aged brain compared to adult brain. Next, binding of the transcription factor NFkappaB to the IL-6 promoter in brains of 1-, 6-, and 24-month-old mice was determined. Electrophoretic mobility shift assay showed that NFkappaB activity was increased in aged brain compared to adult and juvenile brain. Moreover, glial cells cultured from aged mice showed more NFkappaB DNA-binding activity and more IL-6 mRNA and protein expression than glia from adults. However, incubating glia from aged mice in the presence of kappaB decoy inhibited these effects of age. The same was observed in vivo as intracerebroventricular injection of kappaB decoy in aged mice decreased NFkappaB activity and IL-6 mRNA and protein in brain. These results show that the DNA-binding activity of NFkappaB is increased in the brain of aged mice and that at least one consequence is increased expression of IL-6.

Objectives: The DNA-binding activity of nuclear factor kappaB (NFkappaB) is elevated in brain of aged mice, resulting in elevated levels of the inflammatory cytokine interleukin (IL)-6. The purpose of this study was to determine if in the brain of aged mice a decrease in the anti-inflammatory cytokine IL-10 contributes to the increase in IL-6., Methods: In initial studies coronal brain sections and glial cells from adult (6-months-old) and aged (24-months-old) mice were incubated in the presence or absence of lipopolysaccharide (LPS) and the concentrations of IL-6 and IL-10 in supernatants were determined. In subsequent studies, the effect of recombinant murine IL-10 on constitutive and inducible NFkappaB activity, IL-6 mRNA expression and IL-6 protein secretion by glia cultured from brains of adult and aged mice was determined., Results: Coronal brain sections and glia from aged mice secreted more IL-6 and less IL-10 than brain sections and glia from adults. This effect of age was evident in the absence and presence of LPS and suggested that a decrease in IL-10 production permitted increased IL-6 production. Consistent with this idea, treatment of glia from aged mice with recombinant IL-10 decreased both constitutive and inducible binding of NFkappaB to the IL-6 gene promoter. The decrease in NFkappaB activity was associated with a reduction of IL-6 mRNA and protein. Exogenous IL-10, however, had no effect on NFkappaB activity, which was undetectable in unstimulated glia from adult mice, and did not decrease steady-state levels of IL-6 mRNA or IL-6 protein secretion., Conclusions: Collectively, these studies suggest that IL-10 constrained IL-6 gene expression in the adult brain, but in the aged brain it decreased and thus enabled a cascade of intracellular events that increased expression of the IL-6 gene., (Copyright 2002 S. Karger AG, Basel)

Determination of the mercury complex formed with Thiomicher's ketone (TMK) was improved by beta-correction spectrophotometry in the presence of a nonionic surfactant at pH 5. The complex formed was Hg(TMK)2, and its true molar absorptivity is reported for the first time: epsilon Hg(TMK)2(560) = 1.04 x 10(5) L/mol.cm. In addition, the stability constant of Hg(TMK)2 was equal to 3.64 x 10(10) at an ion strength of 0.01 at 20 degrees C. Results from analyses of wastewater samples showed that the relative standard deviations were < or = 8.3%, and the recoveries of mercury ranged from 90 to 110%.

Interleukin-1beta (IL-1beta) is expressed in the mouse brain after intracerebroventricular injection of lipopolysaccharide (LPS) and is thought to be responsible for many of the behavioral and neuroendocrine changes that occur during inflammation. In this study we show that LPS in the brain also induces expression of interleukin-1beta converting enzyme (ICE) and that ICE is important for the characteristic anorectic response of mice to intracerebroventricular LPS. Specifically, mice that were deficient in ICE (ICE(-/-)) resisted the anorexia caused by intracerebroventricular injection of LPS but were sensitive to the anorectic properties of recombinant IL-1beta. The typical anorectic response seen in wild-type (WT) mice after LPS was restored in ICE(-/-) mice by intracerebroventricular administration of the ICE analog cathepsin G. Conversely, anorexia induced by intracerebroventricular injection of LPS in WT mice was blocked by prior intracerebroventricular injection of the ICE antagonist YVAD. CMK. Furthermore, in situ hybridization immunohistochemistry revealed intense expression of ICE mRNA in the hippocampus and dorsomedial hypothalamus of WT mice after intracerebroventricular injection of LPS. Thus ICE mRNA is expressed in brain after intracerebroventricular injection of LPS and is important for induction of anorexia, presumably because it generates mature IL-1beta. These results suggest that preventing generation of mature IL-1beta can inhibit anorexia induced by LPS in the brain and, therefore, reveal ICE as a potential target for regulating food intake during brain inflammation.

In this study, we determined the effects of age and chronic treadmill running (16 wk; 5 days/wk; 45 min/day; 18-22 m/min) on resident peritoneal macrophage responsiveness to interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) in young (6 mo) and aged (22 mo) male BALB/cByJ mice by measuring cytolytic ability and production of reactive nitrogen products. Macrophages (>90% Mac-3(+)) were incubated with various concentrations of IFN-gamma and LPS for 24 h. After washing, P815 tumor cells were utilized as targets in a 16-h 51Cr release assay. We found that aging resulted in a significant reduction in the ability of macrophages to respond to the highest doses of IFN-gamma and LPS and kill P815 cells (46 +/- 4 vs. 34 +/- 2% in young and old mice, respectively). Exercise training significantly increased macrophage cytolysis in both age groups (66 + 7 vs. 44 + 2% in young and old mice, respectively); this effect was larger in the young mice. Macrophages from young exercised mice also produced significantly (50-60%) more NO-2; there was a tendency for higher NO-2 in old exercisers. The inducible nitric oxide synthase (iNOS) inhibitor NG-monomethyl-L-arginine (L-NMMA) significantly reduced macrophage cytolysis and NO-2 production and completely abrogated exercise-induced increases in these measures. RT-PCR analysis revealed significantly higher iNOS mRNA levels in macrophages obtained from the exercise-trained mice and significantly lower iNOS mRNA in old compared with young mice. We conclude that aging reduces and exercise training increases the capacity of resident peritoneal macrophages to respond to IFN-gamma and LPS with increased tumor cytolysis. Enhanced iNOS gene expression and NO-2 production are likely the contributing mechanisms of the exercise-induced enhancement of cytolysis in young mice. While L-NMMA did block the exercise-induced increase in cytolysis, exercise did not increase NO-2 or iNOS gene expression in the old mice, indicating perhaps the contribution of other cytolytic mechanisms in old mice.

Over expression of inflammatory cytokines in the brain may establish a state that is permissive to the onset of neurodegenerative disease. Because the occurrence of certain neurodegenerative diseases increases with age, in the present study we examined the expression of the inflammatory cytokine, interleukin-6 (IL-6), in the brain of aged mice. In an initial experiment, IL-6 was measured in crude protein extracts from brains of juvenile (1-month-old), adult (3-month-old), and aged (24-month-old) male BALB/c mice. The concentration of IL-6 in crude protein extracts from the cerebellum, cerebral cortex, and hippocampus increased with age. The increase in IL-6 was discrete, as levels in the hypothalamus were not age-dependent. To begin evaluating spontaneous IL-6 production in aging, glial cells were cultured from brains of neonate, adult, and aged mice. An age-associated increase in IL-6 mRNA and supernatant IL-6 concentration was evident, indicating glia from aged mice spontaneously express high levels of IL-6 relative to glia from adult and neonate mice. Flow cytometric analysis revealed that cultures established from aged brain compared to either adult or neonate brain comprised more microglia (i.e., MAC-1-positive cells). Furthermore, the proportion of microglia that was positive for IL-6 increased with age, whereas the proportion of astrocytes that were positive for IL-6 was not age-dependent. The present results suggest that IL-6 increases in the mouse brain with age, and that microglia cultured from aged mice spontaneously produce more IL-6 than those from neonate or adult mice. Therefore, microglia may contribute to the increased level of IL-6 present in aged brain.