Environmental Enrichment Promotes Antioxidant Effect in the Ventrolateral Medulla and Kidney of Renovascular Hypertensive Rats / O Enriquecimento Ambiental Promove Efeito Antioxidante no Bulbo Ventrolateral e Rins de Roedores com Hipertensão Renovascular

Abstract Background: Arterial hypertension is a precursor to the development of heart and renal failure, furthermore is associated with elevated oxidative markers. Environmental enrichment of rodents increases performance in memory tasks, also appears to exert an antioxidant effect in the hippocampus of normotensive rats. Objectives: Evaluate the effect of environmental enrichment on oxidative stress in the ventrolateral medulla, heart, and kidneys of renovascular hypertensive rats. Methods: Forty male Fischer rats (6 weeks old) were divided into four groups: normotensive standard condition (Sham-St), normotensive enriched environment (Sham-EE), hypertensive standard condition (2K1C-St), and hypertensive enriched environment (2K1C-EE). Animals were kept in enriched or standard cages for four weeks after all animals were euthanized. The level of significance was at p < 0.05. Results: 2K1C-St group presented higher mean arterial pressure (mmHg) 147.0 (122.0; 187.0) compared to Sham-St 101.0 (94.0; 109.0) and Sham-EE 106.0 (90.8; 117.8). Ventrolateral medulla from 2K1C-EE had higher superoxide dismutase (SOD) (49.1 ± 7.9 U/mg ptn) and catalase activity (0.8 ± 0.4 U/mg ptn) compared to SOD (24.1 ± 9.8 U/mg ptn) and catalase activity (0.3 ± 0.1 U/mg ptn) in 2K1C-St. 2K1C-EE presented lower lipid oxidation (0.39 ± 0.06 nmol/mg ptn) than 2K1C-St (0.53 ± 0.22 nmol/mg ptn) in ventrolateral medulla. Furthermore, the kidneys of 2K1C-EE (11.9 ± 2.3 U/mg ptn) animals presented higher superoxide-dismutase activity than those of 2K1C-St animals (9.1 ± 2.3 U/mg ptn). Conclusion: Environmental enrichment induced an antioxidant effect in the ventrolateral medulla and kidneys that contributes to reducing oxidative damage among hypertensive rats.

Resumo Fundamento: A hipertensão arterial é um precursor para o desenvolvimento da insuficiência cardíaca e renal e, além disso, está associada com o aumento dos marcadores oxidativos. O enriquecimento ambiental dos roedores melhora o desempenho em tarefas de memória, e também parece ter um efeito antioxidante sobre o hipocampo dos ratos normotensos. Objetivos: Avaliar o efeito do enriquecimento ambiental sobre o estresse oxidativo no bulbo ventrolateral, coração, e rins de ratos com hipertensão renovascular. Métodos: Quarenta ratos machos, tipo Fischer (6 semanas de idade), foram divididos em quatro grupos: normotensos em condições padrão (Sham-CP), normotensos em ambiente enriquecido (Sham-AE), hipertensos em condições padrão (2R1C-CP), e hipertensos em ambiente enriquecido (2R1C-AE). Os animais foram mantidos em gaiolas enriquecidas ou padrão durante quatro semanas e, por fim, todos os animais foram eutanasiados. O nível de significância foi p < 0,05. Resultados: O grupo 2R1C-CP apresentou pressão arterial média maior (mmHg) 147,0 (122,0; 187,0) quando comparado com os grupos Sham-CP 101,0 (94,0; 109,0) e Sham-AE 106,0 (90,8; 117,8). Observou-se maior atividade das enzimas superóxido dismutase (SOD) (49,1 ± 7,9 U/mg ptn) e da catalase (0,8 ± 0,4 U/mg ptn) no bulbo ventrolateral do grupo 2R1C-AE, em relação à atividade da SOD (24,1 ± 9,8 U/mg ptn) e da catalase (0,3 ± 0,1 U/mg ptn) no grupo 2R1C-CP. No grupo 2R1C-AE, a oxidação lipídica no bulbo ventrolateral foi menor (0,39 ± 0,06 nmol/mg ptn) quando comparado com o grupo 2R1C-CP (0,53 ± 0,22 nmol/mg ptn). Ademais, foi observada maior atividade das enzimas superóxido dismutase nos rins dos animais 2R1C-AE (11,9 ± 2,3 U/mg ptn) em relação aos animais 2R1C-CP (9,1 ± 2,3 U/mg ptn). Conclusão: O enriquecimento ambiental provocou efeito antioxidante no bulbo ventrolateral e nos rins, o que contribuiu para a redução do dano oxidante nos ratos hipertensos.

Establishment and application of a cell model for LRRC8A physiological characteristic study / 生理学报

The aim of the present study was to establish a cell model of volume-regulated anion channel subunit LRRC8A and investigate the physiological characteristics of LRRC8A. The eukaryotic expression vectors of LRRC8A and YFP-H148Q/I152L were constructed and transfected into Fischer rat thyroid (FRT) cells by Lipofectamine 2000. The FRT cell lines co-expressing LRRC8A and YFP-H148Q/I152L were obtained by antibiotic screening. The expression of LRRC8A and YFP-H148Q/I152L in FRT cells was detected by the inverted fluorescence microscope. The fluorescence quenching kinetic experiment was done to verify the function and effectiveness of the cell model. Then the cell model was utilized to study the physiological characteristics of LRRC8A, such as the characteristics of anion transport, the opening of LRRC8A by osmotic pressure, the effect of anion transport velocity, and the effect of chloride channel inhibitors on LRRC8A anion channel. The results of the inverted fluorescence microscope showed that LRRC8A was expressed on the cell membrane and YFP-H148Q/I152L was expressed in the cytoplasm. The results of fluorescence quenching kinetic test showed that under the condition of low osmotic state, LRRC8A could transport some kinds of anions, such as iodine and chloride ions. Osmotic pressure played a key role in the regulation of LRRC8A volume-regulated anion channel opening. Chloride channel inhibitors inhibited ion transport of LRRC8A channel in a dose-dependent manner. It is suggested that LRRC8A has the characteristics of classic volume-regulated anion channels by using the cell model of FRT cells co-expressing LRRC8A and YFP-H148Q/I152L.

Physical exercise improves body weight gain and liver function in malnourished rats without disturbing the redox balance / O exercício físico melhora o ganho de peso corporal e a função hepática em ratos desnutridos sem perturbar o balanço de redox

ABSTRACT Objective To study the relationship between exercise and malnourishment because recent evidence suggests that exercise can cause the beneficial adaptation of antioxidant systems, whereas malnourishment can cause harmful adaptation of these systems. Methods Thirty-two female Fischer rats were equally divided into Sedentary Control, Trained Control, Sedentary Malnourished and Trained Malnourished groups. The training protocol consisted of swimming for 30 minutes continuously for 5 days/week for 8 weeks. Results It was demonstrated that aspartate aminotransferase and alanine aminotransferase activities increased in malnourished rats, but physical training reversed these effects by lowering the raised levels. The glutathione level was diminished by malnourishment whereas physical training increased the levels of liver carbonyl protein and increased the levels of thiobarbituric acid reactive substances that were diminished by malnourishment. In addition, Trained Malnourished rats had a higher average body weight than Sedentary Malnourished ones (62.77g vs. 55.08g, respectively). Conclusion The data show that exercise was able to reverse or reduce damage caused by malnourishment, such as weight loss and liver dysfunction by a pathway independent of the participation of enzymes involved in antioxidant defense and that there is no interaction between exercise and malnutrition.

RESUMO Objetivo Estudar a relação entre exercício e desnutrição, pois evidências recentes sugerem que o exercício físico pode causar a adaptação benéfica de sistemas antioxidantes, enquanto a desnutrição pode causar adaptação prejudicial a esses sistemas. Métodos Trinta e duas ratas Fischer foram igualmente divididas nos grupos Controle Sedentário, Controle Treinado, Desnutrido Sedentário e Desnutrido Treinado. O protocolo de treinamento consistiu em nadar por 30 minutos continuamente por 5 dias/semana por 8 semanas. Resultados Demonstramos que as atividades de aspartato aminotransferase e alanina aminotransferase aumentaram em ratos desnutridos, mas o treinamento físico reverteu esses efeitos. O nível de glutationa foi diminuído pela desnutrição, enquanto o treinamento físico aumentou os níveis de proteína carbonilada do fígado e aumentou os níveis de substâncias reativas ao ácido tiobarbitúrico que foram diminuídas pela desnutrição. Além disso, os ratos desnutridos treinados tiveram um peso corporal médio maior que os desnutridos sedentários (62,77g vs 55,08g, respectivamente). Conclusão Os dados mostram que o exercício foi capaz de reverter ou reduzir os danos causados pela desnutrição, como perda de peso e a disfunção hepática por uma via independente da participação de enzimas envolvidas na defesa antioxidante e que não há interação entre exercício e desnutrição.

Oxidative stress and sex difference in liver of rats exposed to cyclohexanone / Estrés oxidativo y diferencia sexual en el hígado de ratas expuestas a ciclohexanona

Cyclohexanone is widely used in industry for the organic synthesis of chemicals such as adipic acid, caprolactam, polyvinyl chloride and its copolymers, and methacrylate ester polymers. Its mechanism of toxicity, especially oxidative stress, is rarely reported in cyclohexanone toxicity studies. In this study, we evaluate oxidative stress immunohistochemically in the livers of rats exposed to cyclohexanone. Rats were exposed to 0 ppm and 625 ppm cyclohexanone for 6 h/day, 5 days/week, for 13 weeks via whole-body inhalation. All rats were sacrificed at the end of exposure and livers were removed and prepared for histological examination. Histopathology indicated an increase in bile duct hyperplasia in the liver was only observed in the cyclohexanone-exposed group, compared to that in the control group in males. Immunohistochemistry showed 4-HNE immunoreactivity in the cytoplasm of hepatocytes in the liver. Immunoreactivity was significantly stronger in the cyclohexanone-exposed group compared to the control group in both sexes. However, it was significantly stronger in males compared to females. This result shows a sex-based difference in the expression of oxidative stress in response to cyclohexanone exposure.

La ciclohexanona se usa ampliamente en la industria para la síntesis orgánica de sustancias químicas, como el ácido adípico, la caprolactama, el cloruro de polivinilo y sus copolímeros y los polímeros del éster metacrilato. Su mecanismo de toxicidad, especialmente el estrés oxidativo, se observa raramente en los estudios de toxicidad de la ciclohexanona. En el presente estudio, evaluamos el estrés oxidativo a través de la inmunohistoquímica en hígados de ratas expuestas a la ciclohexanona. Las ratas fueron expuestas a 0 ppm y 625 ppm de ciclohexanona por 6 horas diarias, 5 días a la semana durante 13 semanas, mediante inhalación corporal total. Al final de la exposición, se sacrificaron las ratas y se extirparon sus hígados para el examen histológico. La histopatología indicó que se observó un aumento de la hiperplasia del conducto biliar solamente en el grupo expuesto a la ciclohexanona, en comparación con el grupo de control en machos. La inmunohistoquímica mostró una inmunorreactividad al 4-HNE en el citoplasma de los hepatocitos del hígado. La inmunorreactividad fue significativamente mayor en el grupo expuesto a la ciclohexanona, en comparación con el grupo control en ambos sexos. Sin embargo, fue significativamente mayor en los machos, en comparación con el hígado de las hembras. Este resultado muestra una diferencia basada en el sexo, en la expresión del estrés oxidativo en respuesta a la exposición a la ciclohexanona.

A Single Intraperitoneal Injection of Endotoxin Changes Glial Cells in Rats as Revealed by Positron Emission Tomography Using ¹¹CPK11195 / 대한핵의학회잡지

PURPOSE: Intracranial administration of lipopolysaccharide (LPS) is known to elicit a rapid innate immune response, activate glial cells in the brain, and induce depression-like behavior. However, no study has focused on the changes in glial cells induced by intraperitoneal injection of LPS in vivo.METHODS: Ten adult male Fischer F344 rats underwent [¹¹C]PK11195 PET before and 2 days after intraperitoneal injection of LPS to evaluate the changes in glial cells. The difference in standardized uptake values (SUV) of [¹¹C]PK11195 between before and after injection was determined.RESULTS: There was a cluster of brain regions that showed significant reductions in SUV. This cluster included the bilateral striata and bilateral frontal regions, especially the somatosensory areas.CONCLUSIONS: Changes in activity of glial cells induced by the intraperitoneal injection of LPS were detected in vivo by [¹¹C]PK11195 PET. Intraperitoneal injection of LPS is known to induce depression, and further studies with [¹¹C]PK11195 PET would clarify the relationships between neuroinflammation and depression.

Noni (Morinda citrifolia L.) fruit juice delays immunosenescence in the lymphocytes in lymph nodes of old F344 rats / 中西医结合学报

<p><b>OBJECTIVE</b>Aging is associated with the development of diseases because of immunosuppression and altered functioning of the neuroendocrine system. The medicinal properties of Morinda citrifolia L. have been widely exploited for the treatment of age-associated diseases. This study aims to investigate the in vitro and in vivo effects of noni (M. citrifolia) fruit juice (NFJ) on neuro-immunomodulation in the lymph node lymphocytes of F344 rats.</p><p><b>METHODS</b>Lymphocytes isolated from axillary and inguinal lymph nodes of young (3-4 months) and old (18-21 months) rats were treated in vitro with different concentrations (0.0001%, 0.01%, and 1%) of NFJ for a period of 24 h. In the in vivo study, old (16-17 months) male F344 rats were treated with 5 mL/kg body weight of 5%, 10% and 20% of NFJ, twice a day, by oral gavage, and lymph node lymphocytes were isolated after 60 d. Concanavalin A (Con A)-induced lymphocyte proliferation, interleukin-2 (IL-2) and interferon-γ (IFN-γ) production and expression of intracellular markers, such as phospho-extracellular signal-regulated kinase (p-ERK1/2), phospho-cAMP response element-binding protein, phospho-protein kinase B (p-Akt), phospho-tyrosine hydroxylase (p-TH), phospho-nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor-α (p-IκB-α) and phospho-nuclear factor-κB (p-NF-κB p65 and p50) were examined in the lymphocytes of lymph nodes.</p><p><b>RESULTS</b>NFJ increased Con A-induced lymphocyte proliferation, IL-2 and IFN-γ production, and p-ERK1/2 expression both in vitro and in vivo. In in vivo NFJ-treated old rats, lymph node lymphocytes showed increased expression of p-TH and Akt, nitric oxide production and decreased expression of p-NF-κB p65 and p50.</p><p><b>CONCLUSION</b>These results suggest that the immunostimulatory properties of NFJ are facilitated through intracellular signaling pathways involving ERK1/2, Akt and NF-κB.</p>

Comparison of Changes in the Interstitial Cells of Cajal and Neuronal Nitric Oxide Synthase-positive Neuronal Cells With Aging Between the Ascending and Descending Colon of F344 Rats

BACKGROUND/AIMS: Neuronal degeneration and changes in interstitial cells of Cajal (ICCs) are important mechanisms of age-related constipation. This study aims to compare the distribution of ICCs and neuronal nitric oxide synthase (nNOS) with regard to age-related changes between the ascending colon (AC) and descending colon (DC) in 6-, 31-, and 74-week old and 2-year old male Fischer-344 rats. METHODS: The amount of fecal pellet and the bead expulsion times were measured. Fat proportion in the muscle layer of the colon was analyzed by hematoxylin and eosin staining. Proto-oncogene receptor tyrosine kinase (KIT) and neuronal nitric oxide synthase (nNOS) expression were analyzed with Western blotting and immunohistochemistry. Isovolumetric contractile measurements and electrical field stimulation were used to assess smooth muscle contractility. RESULTS: Colon transit and bead expulsion slowed with senescence. Fat in the muscle layer accumulated with age in the AC, but not in the DC. The proportion of KIT-immunoreactive ICCs in the submucosal and myenteric plexus was higher in the DC than in the AC, and it declined with age, especially in the AC. In contrast, the proportion of NOS-immunoreactive neurons in the myenteric plexus was higher in the AC than in the DC, and both decreased in older rats. Nitric oxide levels declined with age in the DC. Muscle strip experiments showed that the inhibitory response mediated by nitric oxide in the circular direction of the DC was reduced in 2-year old rats. CONCLUSION: The AC and DC differ in their distribution of ICCs and nNOS, and age-related loss of nitrergic neurons more severely affects the DC than the AC.

Potential therapeutic strategies for non - muscle invasive bladder cancer based on association of intravesical immunotherapy with P-MAPA and systemic administration of cisplatin and doxorubicin

ABSTRACT The present study describes the histopathological and molecular effects of P-MAPA (Protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride) intravesical immunotherapy combined with systemic doxorubicin or cisplatin for treatment of non-muscle invasive bladder cancer (NMIBC) in an appropriate animal model. Our results showed an undifferentiated tumor, characterizing a tumor invading mucosa or submucosa of the bladder wall (pT1) and papillary carcinoma in situ (pTa) in the Cancer group. The histopathological changes were similar between the combined treatment with intravesical P-MAPA plus systemic Cisplatin and P-MAPA immunotherapy alone, showing decrease of urothelial neoplastic lesions progression and histopathological recovery in 80% of the animals. The animals treated systemically with cisplatin or doxorubicin singly, showed 100% of malignant lesions in the urinary bladder. Furthemore, the combined treatment with P-MAPA and Doxorubicin showed no decrease of urothelial neoplastic lesions progression and histopathological recovery. Furthermore, Akt, PI3K, NF-kB and VEGF protein levels were significantly lower in intravesical P-MAPA plus systemic cisplatin and in intravesical P-MAPA alone treatments than other groups. In contrast, PTEN protein levels were significantly higher in intravesical P-MAPA plus systemic cisplatin and in intravesical P-MAPA alone treatments. Thus, it could be concluded that combination of intravesical P-MAPA immunotherapy and systemic cisplatin in the NMIBC animal model was effective, well tolerated and showed no apparent signs of antagonism between the drugs. In addition, intravesical P-MAPA immunotherapy may be considered as a valuable option for treatment of BCG unresponsive patients that unmet the criteria for early cystectomy.

Effect of Low Level Subchronic Microwave Radiation on Rat Brain / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>The present study was designed to investigate the effects of subchronic low level microwave radiation (MWR) on cognitive function, heat shock protein 70 (HSP70) level and DNA damage in brain of Fischer rats.</p><p><b>METHODS</b>Experiments were performed on male Fischer rats exposed to microwave radiation for 90 days at three different frequencies: 900, 1800, and 2450 MHz. Animals were divided into 4 groups: Group I: Sham exposed, Group II: animals exposed to microwave radiation at 900 MHz and specific absorption rate (SAR) 5.953 × 10-4 W/kg, Group III: animals exposed to 1800 MHz at SAR 5.835 × 10-4 W/kg and Group IV: animals exposed to 2450 MHz at SAR 6.672 × 10-4 W/kg. All the animals were tested for cognitive function using elevated plus maze and Morris water maze at the end of the exposure period and subsequently sacrificed to collect brain tissues. HSP70 levels were estimated by ELISA and DNA damage was assessed using alkaline comet assay.</p><p><b>RESULTS</b>Microwave exposure at 900-2450 MHz with SAR values as mentioned above lead to decline in cognitive function, increase in HSP70 level and DNA damage in brain.</p><p><b>CONCLUSION</b>The results of the present study suggest that low level microwave exposure at frequencies 900, 1800, and 2450 MHz may lead to hazardous effects on brain.</p>

Research and Design of an Experimental Apparatus Based on the "Open Fireplace" in Xuanwei District / 生物医学工程学杂志

Xuanwei district in Yunnan Province of China has pretty high incidence of lung cancer in China, even a- round the world. Studies have shown that there exists a close relationship between lung cancer and local indoor air pollution caused by Bituminous coal. Considering that the indoor air pollution in Xuanwei District is caused by "open fireplace", an indoor air pollution simulation system was designed, and an F344 rats lung damage model was estab- lished for this indoor air pollution fireplace. The model is based on indoor air pollution simulation system with signal multiplexer control and multi-channel acquisition, and mining PID algorithm was used for polynomial fitting to each test point, and a relatively constant PM2. 5 air pollution status was simulated. The results showed that the system could simulate a variety of states of air pollution, provide a new test method for evaluation of human injury caused by indoor air pollution and a new idea for the study of the incidence of lung cancer in Xuanwei district and other places.

Impact of Long-Term Proton Pump Inhibitor Therapy on Gut Microbiota in F344 Rats: Pilot Study

BACKGROUND/AIMS: To evaluate changes in gut microbiota composition following long-term proton pump inhibitor (PPI) treatment. METHODS: Twenty-four-week-old F344 rats were fed diets with (n=6) or without (n=5) lansoprazole for 50 weeks. Profiles of luminal microbiota in the terminal ileum were then analyzed. Pyrosequencing of the 16S rRNA gene was performed using an FLX genome sequencer (454 Life Sciences/Roche). RESULTS: Rats treated with lansoprazole showed significantly reduced body weights compared to controls (lansoprazole-treated rats and controls, 322.3±15.3 g vs 403.2±5.2 g, respectively, p<0.001). However, stool frequencies and consistencies did not differ between the two groups. The composition of the gut microbiota in lansoprazole-treated rats was quite different from that of the controls. In the controls, the microbiota profiles obtained from the terminal ileum showed a predominance of Proteobacteria (93.9%) due to the abundance of Escherichia and Pasteurella genera. Conversely, lansoprazole-treated rats showed an elevated population of Firmicutes (66.9%), which was attributed to an increased ratio of Clostridium g4 to Lactobacillus genera. CONCLUSIONS: This preliminary study suggests that long-term administration of PPI may cause weight loss and changes to the microbiota in the terminal ileum.

Impact of Long-Term Proton Pump Inhibitor Therapy on Gut Microbiota in F344 Rats: Pilot Study

BACKGROUND/AIMS: To evaluate changes in gut microbiota composition following long-term proton pump inhibitor (PPI) treatment. METHODS: Twenty-four-week-old F344 rats were fed diets with (n=6) or without (n=5) lansoprazole for 50 weeks. Profiles of luminal microbiota in the terminal ileum were then analyzed. Pyrosequencing of the 16S rRNA gene was performed using an FLX genome sequencer (454 Life Sciences/Roche). RESULTS: Rats treated with lansoprazole showed significantly reduced body weights compared to controls (lansoprazole-treated rats and controls, 322.3±15.3 g vs 403.2±5.2 g, respectively, p<0.001). However, stool frequencies and consistencies did not differ between the two groups. The composition of the gut microbiota in lansoprazole-treated rats was quite different from that of the controls. In the controls, the microbiota profiles obtained from the terminal ileum showed a predominance of Proteobacteria (93.9%) due to the abundance of Escherichia and Pasteurella genera. Conversely, lansoprazole-treated rats showed an elevated population of Firmicutes (66.9%), which was attributed to an increased ratio of Clostridium g4 to Lactobacillus genera. CONCLUSIONS: This preliminary study suggests that long-term administration of PPI may cause weight loss and changes to the microbiota in the terminal ileum.

Two-Week Repeated Dose Toxicity of Atractylodis Rhizoma Alba in F344 Rats

This research is to estimate the toxicity of Atractylodis Rhizoma Alba (ARA) in F344 rats and to find a dose level for the 13 weeks toxicity study. A hot water extract of ARA (ARWE) was administered orally to F344 rats at dose levels of 0 (vehicle control), 500, 1000, 2000, 3500, and 5000 mg/kg/day for 2 weeks. Each group was composed to five male and five female F344 rats. According to the result, there were no ARWE-related adverse changes in mortality, body weights, food consumption, urinalysis, hematology, clinical chemistry, gross finding at necropsy, and organ weight examination. Salivation was observed in 3500 and 5000 mg/kg/day in male and female rats but it could not have found any relationship with ARWE administration. Based on our findings, ARWE may not cause toxicity in rats under the experimental conditions. Therefore, dose level of 5000 mg/kg/day as a highest treatment group in 13-week exposure study is recommended for further toxicity assessment.

Ethnopharmacology, phytochemistry, and biological activities of Cymbopogon citratus (DC.) Stapf extracts / 中国天然药物

Cymbopogon citratus is a widely distributed perennial herb belonging to the Poaceae family and has been extensively consumed for its medicinal, cosmetic, and nutritional effects for centuries. A large number of reports have been published describing the pharmacological, biological, and therapeutic actions of this herb. In this review, we summarized the literatures on related studies (up to January, 2014) that highlighted the pharmacologic and biological effects of the major phytochemicals isolated from C. citratus extracts and its essential oil. The components of the essential oils found in C. citratus have a similar pharmacokinetic properties, including absorption, distribution, metabolism, and excretion. They are quickly absorbed following oral, pulmonary, and dermal administration. Based on the published reports, it can also be inferred that, after absorption from the small intestine, some phytochemicals in C. citratus can undergo oxidation, glucuronidation, sulfation, and/or O-methylation. Excretion is through urine, feces and/or expired volatiles. The biotransformation reactions of C. citratus bioactive constituents are essential for its relatively safe consumption and therapeutic applications. The data available so far warrant further studies evaluating C. citratus pharmacokinetics. Reliable pharmacokinetic data in humans would be critical for a better understanding of the the systemic handling of C. citratus.

Effects of propofol on pulmonary metastasis of intravenously injected MADB106 tumor cells and expression of E-cadherin and β-catenin in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of different doses of propofol on pulmonary metastasis of intravenous injected MADB106 tumor cells and the expression of E-cadherin and β-catenin in the metastatic tumor tissue in rats.</p><p><b>METHODS</b>Forty Fischer 344 male rats were randomly divided into 4 groups (n=10) for intravenous administration of normal saline, intralipid, or propofol at 30 or 50 mg/kg via the femoral vein. One hour after the infusion, MADB106 tumor cells (2×10(5)) were injected intravenously in the rats. Three weeks later, pulmonary metastasis tumor foci and metastatic inhibitory rate were observed and the expression of E-cadherin and β-catenin in the metastatic tumor tissue were detected by immunohistochemistry.</p><p><b>RESULTS</b>Compared with the normal saline group, intralipid group showed no significant differences in the number of metastatic tumor foci in the lungs or E-cadherin and β-catenin expressions (P>0.05), which were all significantly lowered in the two propofol groups (P<0.05 or 0.01). The dose of propofol was inversely correlated with the number of metastasis tumor foci (r=-0.879) and expressions of E-cadherin (r=-0.755) and β-catenin (r=-0.693) (P<0.01).</p><p><b>CONCLUSION</b>Propofol can dose-dependently suppress pulmonary metastasis of intravenous injected MADB106 tumor cells by inhibiting the Wnt/β-catenin pathway and down-regulating E-cadherin and β-catenin expressions in the metastatic tumor tissue.</p>

Root Resorption in Streptozotocin-induced Diabetic Rats with Ligature-induced Periodontitis

To determine the effect of diabetes on root resorption in periodontitis, we investigated odontoclast formation and root resorption in diabetic rats with periodontitis. Odontoclast formation was observed in three groups of F344 rats: Controls (C) were normal rats without diabetes or periodontitis; the periodontitis (P) group had mandibular first molars to be ligatured; the periodontitis with diabetes (PD) group was intravenously administered streptozotocin (50 mg/kg) to induce diabetes and had mandibular first molars to be ligatured. On days 3, 10, and 20 after ligature, tumor necrosis factor (TNF)-alpha and receptor activator of nuclear factor-kappaB ligand (RANKL) expression, odontoclast formation, and root resorption areas were evaluated by immunohistochemistry, tartrate-resistant acid phosphatase staining, and hematoxylin and eosin staining, respectively. The PD group showed frequent urination, weight loss, and hyperglycemia. Numbers of TNF-alpha- and RANKL-positive cells were higher in the P and PD groups than in the C group. It was more prevalent in PD group on day 3. Odontoclast formation was greater in the P and PD groups than in the C group on days 3 and 10, then decreased to same level as the C group by day 20. Root resorption in the PD and P groups showed increases on days 3 and 10, respectively, compared to the C group. These results suggest that diabetes may transiently increase root resorption on day 3 with high expression of TNF-alpha and RANKL after periodontitis induction. This study could aid the understanding of root resorption in diabetic patients with periodontitis.

A 14-Day Repeated Dose Toxicity of Epimedii Herba Aqueous Extract Administered by Oral Gavage in F344 Rats

The objective of this study is to characterize a toxicity of Epimedii Herba (EH) in F344 rats and to find a dose levels for the 13 weeks toxicity study. EH is well known as medicinal herb in many Asian countries for traditional medicines of antibacterial and antiviral effects, estrogenic and antiestrogenic effects, and for treatment of osteoporosis, hypotensives, fatigue, kidney disorders, and related complications. However, the indispensable and basic information of toxicological evaluation of EH extract is insufficient to support its safe use. Therefore, we conducted toxicological evaluation of this drug in compliance with OECD and MFDS guideline in this study. The extract of EH was administered orally to F344 rats at dose levels of 0, 500, 1000, 2000, 3500, and 5000 mg/kg/day for 2 weeks. Each group was composed of 5 male and female rats. In this study, there were no treatment of EH-related adverse changes in clinical observations, mortality, body weights, food consumption, urinalysis, gross finding at necropsy, and organ weight examination. Total red blood cell count, hematocrit, mean corpuscular hemoglobin concentration, total cholesterol, and phospholipid were decreased in males and females at 5000 mg/kg/day compared to the control animals. Mean corpuscular volume and reticulocyte counts were increased in males and females at 5000 mg/kg/day compared to control animals. Therefore, we recommend that dose level of 5000 mg/kg/day is a highest treatment group in 13-week EH extract exposure study for further toxicity assessment.

4-(Methylnitrosamino)-1-(3-pyridyl) -1-butanone induces circulating microRNA deregulation in early lung carcinogenesis / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To study the alteration of circulating microRNAs in 4-(methylnitrosamino)-1-(3-pyridyl) -1-butanone (NNK)-induced early stage lung carcinogenesis.</p><p><b>METHODS</b>A lung cancer model of male F344 rats was induced with systemic NNK and levels of 8 lung cancer-associated miRNAs in whole blood and serum of rats were measured by quantitative RT-PCR of each at weeks 1, 5, 10, and 20 following NNK treatment.</p><p><b>RESULTS</b>No lung cancer was detected in control group and NNK treatment group at week 20 following NNK treatment. The levels of some circulating miRNAs were significantly higher in NNK treatment group than in control group. The miR-210 was down-regulated and the miR-206 was up-regulated in NNK treatment group. The expression level of circulating miRNAs changed from week 1 to week 20 following NNK treatment.</p><p><b>CONCLUSION</b>The expression level of circulating miRNAs is related to NNK-induced early stage lung carcinogenesis in rats and can therefore serve as its potential indicator.</p>

An expression analysis of miR-200a in serum and liver tissue during the process of liver cancer development in rats / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore whether microRNA-200a (miR-200a) could be used as a novel biomarker of liver cancer using a rat model system.</p><p><b>METHODS</b>Diethylnitrosamine abdominal injection was applied to induce liver cancer in the F344 rat strain (n =40); ten unmodeled rats served as controls. In addition, human subjects with normal healthy liver (n =10), liver cirrhosis (n =10), and liver cancer (n =10) were enrolled in the study. Blood samples from both rats and patients and rats' livers were collected for analysis. Real-time quantitative PCR and enzyme-linked immunosorbent assay were used respectively to measure the expressions of serum miR-200a and alpha-fetoprotein (AFP) for all rat and human subjects. In situ hybridization was used to detect the miR-200a expression in the rats' livers.</p><p><b>RESULTS</b>Comparison of normal rats and the liver cancer modeled rats showed that the latter had significantly lower expression of miR-200a (P less than 0.05), with decreasing expression following the progression of liver injury to cancer (liver cirrhosis rats less than early liver cancer rats less than advanced liver cancer rats); in contrast, the AFP levels were significantly higher in the liver cancer modeled rats only at the early and advanced stages of the liver cancer (P less than 0.05). These</p><p><b>RESULTS</b>suggested that miR-200a expression decreases during the developmental process of liver cancer, while AFP expression increases distinctly at the stage of tumor formation. Analysis of the human subjects' clinical samples showed that miR-200a expression was decreased in both liver cirrhosis patients and liver cancer patients (vs. normal liver subjects, P less than 0.05), while AFP showed abnormal expression only in the patients with liver cancer. Comparison of the normal rats and modeled rats using in situ hybridization showed the positive rates for miR-200a expression were 1.00% +/- 0.01% in rats with normal liver, 0.37% +/- 0.03% in rats with fibrotic liver, 0.14% +/- 0.01% in rats with cirrhotic liver, 0.05% +/- 0.00% in rats with early stage liver cancer, and 0.01% +/- 0.00% in rats with advanced stage liver cancer.</p><p><b>CONCLUSION</b>MiR-200a may play an important role in liver cancer development and may have diagnostic value for indicating early liver cancer.</p>

Effects of propofol on pulmonary metastasis of intravenous injected tumor cells and expressions of MTA1 and Wnt1 in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of different doses of propofol on pulmonary metastasis of intravenous injected tumor cells and expression of MTA1 and Wnt1 in the metastatic tumor in rats.</p><p><b>METHODS</b>Forty male Fischer344 rats were randomly divided into 4 equal groups for intravenous administration of normal saline, intralipid, or propofol at the dose of 30 or 50 mg/kg pumped via the femoral vein. One hour after the infusion, MADB106 tumor cells (2×10) were injected intravenously in the rats. Pulmonary metastasis of the tumor cells was observed and the expression of MTA1 and Wnt1 in the metastatic tumor detected by immunohistochemistry 3 weeks later.</p><p><b>RESULTS</b>The rats receiving saline and intralipid treatments showed a comparable number of pulmonary metastasis and similar expression levels of MTA1 and Wnt1 in the metastatic tumor (P>0.05); the tumor number and MTA1 and Wnt1 were significantly lower in the two propofol groups (P<0.01). The doses of propofol was inversely correlated with the number of pulmonary metastasis (r=-0.879) and expressions of MTA1 (r=-0.980) and Wnt1 (r=-0.916) (P<0.01), and MTA1 and Wnt1 expression levels in the metastatic tumors were closed correlated (r=0.902, P<0.01).</p><p><b>CONCLUSION</b>Propofol can dose-dependently suppress pulmonary metastasis of intravenously injected tumor cells and down-regulate MTA1 and Wnt1 expressions in the metastatic tumor tissue.</p>