Serum Biochemical Tests Research Articles

Betulin attenuates lung and liver injuries in sepsis

Sepsis is a complex condition with unacceptable mortality. Betulin is a natural extract with multiple bioactivities. This study aims to evaluate the potential effects of betulin on lung and liver injury in sepsis. Cecal ligation and puncture was used to establish the rat model of sepsis. A single dose of 4mg/kg or 8mg/kg betulin was injected intraperitoneally immediately after the model establishment. The survival rate was recorded every 12h for 96h. The organ injury was examined using hematoxylin and eosin staining and serum biochemical test. The levels of proinflammatory cytokines and high mobility group box 1 in the serum were measured using ELISA. Western blotting was used to detect the expression of proteins in NF-κB and MAPK signaling pathways. Betulin treatment significantly improved the survival rate of septic rats, and attenuated lung and liver injury in sepsis, including the reduction of lung wet/dry weight ratio and activities of alanine aminotransferase and aspartate aminotransferase in the serum. In addition, levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 and high mobility group box 1 in the serum were also lowered by betulin treatment. Moreover, sepsis-induced activation of the NF-κB and MAPK signaling pathway was inhibited by betulin as well. Our findings demonstrate the protective effect of betulin in lung and liver injury in sepsis. This protection may be mediated by its anti-inflammatory and NF-κB and MAPK inhibitory effects.

Single-dose Intramuscular-injection Toxicology Test of Water-soluble Carthami-flos and Cervi cornu parvum Pharmacopuncture in a Rat Model.

Objectives:The aim of the study is to investigate both the single-dose intramuscular injection toxicity and the approximate lethal dose of water-soluble Carthami-flos and Cervi cornu parvum pharmacopuncture (WCFC) in male and female Sprague-Dawley (SD) rats.Methods:The study was conducted at Biotoxtech Co. according to the Good Laboratory Practice (GLP) regulation and the toxicity test guidelines of the Ministry of Food and Drug Safety (MFDS) after approval of the Institutional Animal Care and Use Committee. Dosages for the control, high dose, middle dose and low dose groups were 0.5 mL/animal of saline and 0.5, 0.25 and 0.125 mL/animal of WCFC, respectively. WCFC was injected into the muscle of the left femoral region by using a disposable syringe (1 mL, 26 gauge). The general symptoms and mortality were observed 30 minutes, 1, 2, 4, and 6 hours after the first injection and then daily for 14 days after the injection. The body weights of the SD rats were measured on the day of the injection (before injection) and on the third, seventh, and fourteenth days after the injection. Serum biochemical and hematologic tests, necropsy examinations, and histopathologic examinations at the injection site were performed after the observation period.Results:No deaths, abnormal clinical symptoms, or significant weight changes were observed in either male or female SD rats in the control or the test (0.125, 0.25, and 0.5 mL/animal) groups during the observation period. No significant differences in hematology and serum biochemistry and no macroscopic abnormalities at necropsy were found. No abnormal reactions at injection sites were noted on the topical tolerance tests.Conclusion:The results of this single-dose toxicity study show that WCFC is safe, its lethal doses in male and female SD rats being estimated to be higher than 0.5 mL/animal.

Reduction in sodium intake is independently associated with improved blood pressure control in people with chronic kidney disease in primary care.

Decreasing sodium intake has been associated with improvements in blood pressure (BP) and proteinuria, two important risk factors for CVD and chronic kidney disease (CKD) progression. We aimed to investigate the role of sodium intake by examining the effect of changes in sodium intake over 1 year on BP and proteinuria in people with early stage CKD. From thirty-two general practices, 1607 patients with previous estimated glomerular filtration rate of 59-30 ml/min per 1.73 m² and mean age of 72.9 (sd 9.0) years were recruited. Clinical assessment, urine and serum biochemistry testing were performed at baseline and after 1 year. Sodium intake was estimated from early morning urine specimens using an equation validated for this study population. We found that compared with people who increased their sodium intake from ≤ 100 to >100 mmol/d over 1 year, people who decreased their intake from >100 to ≤ 100 mmol/d evidenced a greater decrease in all BP variables (Δmean arterial pressure (ΔMAP) = -7.44 (SD 10.1) v. -0.23 (SD 10.4) mmHg; P<0.001) as well as in pulse wave velocity (ΔPWV = -0.47 (SD 1.3) v. 0.08 (SD 1.88) m/s; P<0.05). Albuminuria improved only in albuminuric patients who decreased their sodium intake. BP improved in people who maintained low sodium intake at both times and in those with persistent high intake, but the number of anti-hypertensive increased only in the higher sodium intake group, and PWV improved only in participants with lower sodium intake. Decreasing sodium intake was an independent determinant of ΔMAP. Although more evidence is needed, our results support the benefits of reducing and maintaining sodium intake below 100 mmol/d (2.3-2.4 g/d) in people with early stages of CKD.

Safety Evaluation of Hemoglobin-Albumin Cluster "HemoAct" as a Red Blood Cell Substitute.

A hemoglobin (Hb) wrapped covalently by human serum albumins (HSAs), a core–shell structured hemoglobin-albumin cluster designated as “HemoAct”, is an O2-carrier designed for use as a red blood cell (RBC) substitute. This report describes the blood compatibility, hemodynamic response, and pharmacokinetic properties of HemoAct, and then explains its preclinical safety. Viscosity and blood cell counting measurements revealed that HemoAct has good compatibility with whole blood. Intravenous administration of HemoAct into anesthetized rats elicited no unfavorable increase in systemic blood pressure by vasoconstriction. The half-life of 125I-labeled HemoAct in circulating blood is markedly longer than that of HSA. Serum biochemical tests conducted 7 days after HemoAct infusion yielded equivalent values to those observed in the control group with HSA. Histopathologic inspections of the vital organs revealed no marked abnormality in their tissues. All results indicate that HemoAct has sufficient preclinical safety as an alternative material for RBC transfusion.

Use of a point-of-care portable blood analyzer for evaluation of blood gas analytes and select physiologic parameters in the American flamingo (Phoenicopterus ruber)

This study was conducted in order to evaluate blood gas analytes using a portable clinical analyzer in captive American flamingos (Phoenicopterus ruber). Seventeen healthy flamingos were evaluated as part of an overall clinical health assessment. Each bird underwent a complete physical examination, complete blood count, and serum biochemistry testing. Blood samples were collected from the medial metatarsal vein and using the VetScan i-STAT® analyzer, tested for the following parameters: hydrogen ion concentration, oxygen tension, carbon dioxide tension, sodium, potassium, ionized calcium, hematocrit, and various calculated parameters. The different parameters of venous blood gas were described using the mean, median, the interquartile range, P2.5 and P97.5, and minimum and maximum values. A comparison between sexes revealed no significant difference (p > 0.05) in any of the observed values. The test provided rapid results and was easy to use, making it useful for point-of-care use in zoological settings, or hospitalized critical avian patients. Knowledge of baseline parameters can promote better physiological understanding and improve clinical management of this avian species.

Antioxidant Activity and Hepatoprotective Potential of &lt;i&gt;Artemisia aucheri&lt;/i&gt; in Rat

Background/Objectives: Medicinal plants play an important role in human health. A large number of plants have claimed for hepatoprotective potential. The aim of this study was to assay the hepatoprotective potential of hydro alcoholic extract of on Carbon tetrachloride induced hepatotoxicity in rats. Materials and methods: Hydro alcoholic extract of Artemisia aucheri at dose of 150, 300 and 600 mg/kg administered on rats for 28 days. The hepatoprotective effect was assessed by serum biochemical tests such as alaine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, total protein and albumin. Antioxidant enzymes (superoxide dismutase and catalase), malondialdehyde, F2α-isoprostanes and reduced glutathione were determined along with histopathological studies on liver tissue. Results: Serum levels of total protein, albumin, superoxide dismutase, catalase activities and reduced glutathione were decreased in carbon tetrachloride (toxin) group. However alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, malondialdehyde, F2α-isoprostanes were increased. In treatment groups all biochemical parameters restored toward normal by use of hydroalcoholic extract of A. aucheri. Conclusion: Hydro alcoholic extract of Artemisia aucheri displayed protective potential against carbon tetrachloride induced hepatotoxicity which demonstrated by biochemical tests in tissue homogenate and serum. Also histopathological studies in liver tissue

Colocolonic Intussusception Secondary to Lipoma.

A 44-year-old-woman was admitted to our hospital with a 7-day history of abdominal pain. The pain was non-continuous, generalized and colicky in nature. Physical examination showed diffuse abdominal tenderness. The results of the serum biochemistry tests were within normal limits. Plain film of the abdomen showed a few air-fluid levels.

Bioimpedance spectroscopy for the differential diagnosis of hyponatremia

Background: Hyponatremia is classified according to volume status with the help of physical examination, biochemical measures, urine and serum osmolalities, and echocardiography. Bioimpedance spectroscopy (BIS) has been getting popularity for revealing tissue compositions of various patient groups. The aim of this observational study was to investigate the role of BIS for the differential diagnosis of hyponatremia (ClinicalTrials.gov Identifier: NCT01838759). Patients and methods: Personal characteristics of age, sex, weight, height, and blood pressure were recorded. Body composition monitor (BCM) was used for hydration status for each individual. Primary outcome was investigated by the accuracy of volume status measured by BIS. Statistics: Kappa statistic (K) is a measure of agreement between two sources, which is measured on a binary scale (i.e., condition present/absent). K statistic can take values between 0 and 1: poor agreement: K < 0.20, fair agreement: 0.2.0–0.3.9, moderate agreement: 0.40–0.59, substantial: 0.60–0.79, very good agreement: 0.80–1.00. Results: Fifty-eight hyponatremia-diagnosed patients, 32 (55.2%) of male with the mean age of 65.2 ± 11 (40–89) years were included. Kappa statistic (K) were very good (K = 0.925) for male (p < 0.00), substantial agreement (K = 0.601) for female (p < 0.002) with the use of BIS for the differential diagnosis of either hypo or hypervolemia in hyponatremic patients compared with gold standard tests which were the combination of echocardiography, serum, and urine osmolality biochemical tests, and physical examination. Conclusion: Bioimpedance spectroscopy is a practical and an inexpensive method. This is the first study in the literature showing the role of BIS for the determination of the volume status and differential diagnosis of hyponatremia when compared with echocardiography.

The inhibition of hepatic bile acids transporters Ntcp and Bsep is involved in the pathogenesis of isoniazid/rifampicin-induced hepatotoxicity

Co-treatment of isoniazid (INH) and rifampicin (RFP) is well known for clinically apparent liver injury. However, the mechanism of INH/RFP-induced liver injury is controversial. Emerging evidence shows links between inhibition of bile acids transporters and drug-induced liver injury (DILI). The present study investigates whether sodium taurocholate cotransporting polypeptide (NTCP/Ntcp; SLC10A1) and bile salt export pump (BSEP/Bsep; ABCB11) are involved in the anti-tuberculosis medicines induced liver injury. ICR female mice were intragastrically treated with INH (50 or 100 mg/kg), RFP (100 or 200 mg/kg), or the combination of INH/RFP (50 + 100 mg/kg or 100 + 200 mg/kg) for 14 consecutive days. Liver histopathological examination, serum biochemical and liver malondialdehyde tests were evaluated. Apparent histopathological alterations and hepatic oxidative stress showed in INH (100 mg/kg), RFP (200 mg/kg) and their combination group. The hepatoxic effect was also indicated by increased serum biomarkers, such as aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), direct bilirubin (DBil), total bilirubin (TBil) and total bile acids (TBA). Both doses of INH/RFP administration significantly down-regulated the expression of Ntcp and Bsep in liver. Furthermore, the combination of INH and RFP displayed stronger effect on the expression of Ntcp compared with the corresponding dose of INH or RFP alone. In conclusion, down-regulated expression of hepatic Ntcp and Bsep might play an important role in the development of INH and RFP induced liver injury.

The study of the anti‐obesity effect of dairy administration green tea extract in high fat diet induced obese rats

In the previous researches, several anti-obesity mechanisms were described such as induction of LPL expression and anti-oxidant activity. Green tea polyphenols have also been reported to have beneficial effects of against obesity. However, the mechanism is not clear. The aim of this study was to assess anti-obesity effect of green tea extract (GTE) in obese rat model. Thirty male SD rats were divided into three groups as follows: the control group (rats fed with normal diet;C group), the HE group (rats fed with high-fat diet;HE group), and the HE+GTE group (rats fed with high-fat diet and GTE by oral;HEG group). After eight weeks, body weight, feed efficiency, body composition, body fat percentage, serum biochemical tests, lipoprotein lipase (LPL) activity assays, TG and TC in liver were measured to evaluate the anti-obesity effects. GTE supplementation significantly enhanced body composition, decreased body fat percentage, and reduced the level of TG and TC in serum and liver. Furthermore,the up-regulation of LPL and antioxidant genes was observed in the GTE supplemented groups. The results revealed that the beneficial effects of GTE may via modulating LPL activity to decrease on body weight.

Serum bile acids concentration in captive American flamingos (Phoenicopterus ruber)

This study was conducted in order to determine serum bile acids concentration in captive American flamingos (Phoenicopterus ruber). Seventeen healthy flamingos of both sexes were evaluated as part of an overall clinical health assessment. Each bird underwent a complete physical examination, complete blood count, and serum biochemistry testing. Blood samples were collected from the medial metatarsal vein and submitted for a serum bile acids analysis. The median serum bile acids concentration for the American flamingo was 30 μmol/L (min = 20 μmol/L, max = 58 μmol/L), with no significant difference (p = 0.14) between males and females in this study. The data presented in this report can promote better physiological understanding and improve clinical management of this avian species.

Low molybdenum state induced by tungsten as a model of molybdenum deficiency in rats.

Organ molybdenum (Mo) concentration and the activity of hepatic sulfite oxidase and xanthine oxidase were compared in tungsten-administered rats as well as rats fed with a low Mo diet to evaluate the use of tungsten-administered rats as a model of Mo deficiency. Twenty-four male 6-week-old Wistar rats were divided into four groups according to diet (AIN93G diet (control diet) or the control diet minus ammonium molybdate (low Mo diet)) and drinking water (deionized water or deionized water containing 200 μg/mL tungsten in the form of sodium tungstate). Mo content in the control and low Mo diets were 196 and 42 ng/g, respectively. Intake of the low Mo diet significantly reduced the Mo content of several organs and serum. Decrease in hepatic sulfite oxidase activity was also induced by the low Mo diet. The administration of tungsten induced marked decreases in organ Mo content and the activity of hepatic sulfite oxidase and xanthine oxidase. These decreases induced by tungsten administration were more pronounced than those induced by just a low Mo diet. Serum uric acid was also reduced by tungsten administration irrespective of Mo intake. Although a comparatively high accumulation of tungsten (3 to 9 μg/g) was observed in the kidneys and liver, adverse effects of tungsten accumulation on liver and kidney function were not observed in serum biochemical tests. These results indicate that tungsten-administered animals may be used as a model of Mo deficiency.

Development of biodegradable radiopaque microsphere for arterial embolization-a pig study.

To develop a new type of calibrated, biodegradable, and imaging detectable microsphere and evaluated its embolization safety and efficacy on pig's liver and spleen. Six kinds of pharmaceutical excipient were combined and atomized to form our microsphere. Twenty-four male Lanyu pigs weighing 25-30 kg were used. The arteries of spleen and liver were embolized with Gelfoam, Embosphere, or our microsphere. The serum biochemical tests, computed tomography (CT), liver perfusion scan, and tissue microscopy examination were done to evaluate the safety and efficacy of embolization. Radiopaque microspheres with a size ranging from 300 to 400 μm were produced. Embolization of hepatic and splenic artery of pigs with our microsphere significantly reduced the blood flow of liver and resulted in splenic infarction. The follow-up CT imaging and the microscopic examination showed intraarterial degradation of Gelfoam and microsphere. The blood tests demonstrated insignificant changes with regards to liver and renal functions. Our microspheres, with the unique characteristics, can be used for transcatheter arterial embolization with effects equivalent to or better than Gelfoam and Embosphere in pigs.

In Vitro and in Vivo Antioxidant Related Effects of Rosemary (&amp;lt;i&amp;gt;Rosmarinus Officinalis&amp;lt;/i&amp;gt; L.) Extracts in Humans

Rosemary (Rosmarinus officinalis L.) belongs to the family Lamiaceae (Labiatae) is a well-known aromatic plant used all around the world for different medicinal purposes. Aims: The present work aimed to investigate antioxidant related effects of rosemary in humans by in vitro and in vivo studies. Study design: Chemical antioxidant assays and venous blood from healthy volunteers were used to conduct in vitro experiments. For in vivo study, nine healthy volunteers, each received orally 250 ml of aqueous extract of rosemary daily for 5 days. Venous bloods were taken before and one hour after the first dose of aqueous extract (sample I and II respectively) and then one day after the last dose of day five (i.e. day 6, sample III). The first blood taken before the first dose (i.e. sample I), served as control for the next samples of II and III. Methodology: The following assays were performed: total antioxidant capacity (TAC), reducing power, scavenging activity of DPPH, scavenging activity of OH, iron chelating ability, erythrocyte reduced glutathione (GSH), malonyldialdehyde (MDA), protein carbonyl (PC), superoxide dismutase (SOD), percentage hemolysis, serum total antioxidant status (TAS) and serum selected biochemical tests. Results: Rosemary extract showed efficient total antioxidant capacity, reducing power, scavenging activity of DPPH, scavenging activity of OH and a reasonable iron chelating ability. Pre-incubation of erythrocytes in vitro with methanolic extract of rosemary then exposed to H₂O₂ decreased significantly MDA production (i.e. anti-lipid-peroxidant), PC production (i.e. anti-protein-oxidant) and oxidant hemolysis (i.e. anti-hemolytic) in a concentration dependent manner. Oral administration of aqueous extracts of rosemary to healthy volunteers, for 5 days, increased significantly serum TAS (18% increase), erythrocyte GSH (72% increase), erythrocyte superoxide dismutase (SOD) (21% increase) and decreased significantly erythrocyte MDA (17% decrease), with no effect on serum biochemical tests for kidney, liver, cardiac and pancreatic, compared to 0 time administration. Conclusion: Rosemary extracts have efficient in vitro and in vivo antioxidant related effects. As the present findings are obtained in healthy humans with no oxidative stress, this indicates that rosemary can improve the base line of the defense mechanisms against possible oxidative stress, with no adverse effects, thus decreasing susceptibility or preventing the progress of pathological conditions related to oxidative stress.

A Retrospective Study of the Medical Status on 63 African Hedgehogs (Atelerix albiventris) at the Taipei Zoo From 2003 to 2011

Inbreeding of African hedgehogs (Atelerix albiventris) is considered a problem as breeders try to meet the demands of the pet trade. Most studies of African hedgehogs are concentrated in the USA. This study investigates and compares the life span and medical conditions of captive African hedgehogs at the Taipei Zoo, Taiwan. The medical records of 63 African hedgehogs at the Taipei Zoo from 2003 to 2011 were collected and analyzed statistically for this retrospective study. The mean life span of the 39 deceased hedgehogs in the study was 3.4 ± 1.1 years. The average weight was 401 ± 98g. Female hedgehogs were heavier than males. The primary cause of death in this group of animals was neoplasia (35.9%). Oral squamous cell carcinoma was the most common form of neoplasia diagnosed (35.7%). Hematologic and serum biochemical tests from 9 healthy adults revealed increased alanine aminotransaminase, aspartate aminotransferase, total bilirubin, and albumin values compared with references. Decreased values for alkaline phosphatase, amylase, and creatinine levels were also found. The results of this study may provide a better understanding of African hedgehog health and may help to determine potential management problems.

Protective effects of resveratrol on hepatotoxicity induced by isoniazid and rifampicin via SIRT1 modulation.

Acute liver injury was induced in male BALB/c mice by coadministering isoniazid and rifampicin. In this work, the effects of resveratrol (1) were investigated in the hepatotoxicity caused by isoniazid-rifampicin in mice. Compound 1 was administered 30 min prior to isoniazid-rifampicin. Serum biochemical tests, liver histopathological examination, oxidative stress, myeloperoxidase activity, cytokine production (TNF-α, IL-12p70, and IL-10), and mRNA expression of SIRT1-7 and PPAR-γ/PGC1-α were evaluated. The administration of 1 significantly decreased aspartate transaminase and alanine aminotransferase levels, myeloperoxidase activity, and cytokine levels. Furthermore, 1 reverted the decrease of catalase and glutathione activities and ameliorated the histopathological alterations associated with antituberculosis drugs. Modulation of SIRT1 and PPAR-γ/PGC1-α expression is likely involved in the protective effects of 1. The results presented herein show that 1 was able to largely prevent the hepatotoxicity induced by isoniazid and rifampicin in mice, mainly by modulating SIRT1 mRNA expression.

High sodium intake is associated with important risk factors in a large cohort of chronic kidney disease patients.

An increased risk of mortality and cardiovascular disease (CVD) is observed in people with chronic kidney disease (CKD) even in early stages. Dietary sodium intake has been associated with important CVD and CKD progression risk factors such as hypertension and proteinuria in this population. We aimed to investigate the relationship between sodium intake and CVD or CKD progression risk factors in a large cohort of patients with CKD stage 3 recruited from primary care. A total of 1733 patients with previous estimated glomerular filtration rate (eGFR) of 30-59 ml/min/1.73m(2), with a mean age 72.9±9.0 years, were recruited from 32 general practices in primary care in England. Medical history was obtained and participants underwent clinical assessment, urine and serum biochemistry testing. Sodium intake was estimated from three early-morning urine specimens using an equation validated for this study population. Sixty percent of participants who had estimated sodium intake above recommendation (>100 mmol/day or 6 g salt/day) also had higher diastolic blood pressure, mean arterial pressure (MAP), urinary albumin-to-creatinine ratio, high-sensitive C-reactive protein and uric acid and used a greater number of anti-hypertensive drugs. In multivariable regression analysis, excessive sodium intake was an independent predictor of MAP (B=1.57, 95% confidence interval (CI) 0.41-2.72; P=0.008) and albuminuria (B=1.35, 95% CI 1.02-1.79; P=0.03). High sodium intake was associated with CVD and CKD progression risk factors in patients with predominantly early stages of CKD followed up in primary care. This suggests that dietary sodium intake could afffect CVD risk even in early or mild CKD. Intervention studies are warranted to investigate the potential benefit of dietary advice to reduce sodium intake in this population.

English

This experiment evaluated the 28-day feeding study in rats after they were continuously fed with multi-species probiotics dosages in the low-dosage, medium-dosage, and high-dosage groups: 2,000 mg/kg body weight (B.W.), 4,000 mg/kg B.W., and 6,000 mg/kg B.W., respectively, for 28 days as a reference for the safety of its repeated usage. Each group consisted of 10 male and 10 female Sprague-Dawley (SD) rats and the test substance was administered for 28 continuous days. After the experiment, the rats were sacrificed, and their blood and viscera were collected for haematological analysis, serum bio-chemical analysis, and pathological examination. The test results showed that, during the experiment, none of the tested rats exhibited abnormal clinical symptoms; the rats in all dosage groups gained weight normally. At the end of the test, the results of urological testing, haematological testing, and serum biochemical testing revealed no significant differences between the dosage groups and the control group. The results of the pathological dissection, the macroscopic inspection of pathological changes, and the histopathological inspection revealed no significant pathological changes related to the tested substance in the dosage groups and the control group. Key words: Probiotics, Sprague-Dawley rat, haematological analysis, serum biochemical analysis, pathological examination.

Regorafenib suppresses sinusoidal obstruction syndrome in rats

BackgroundSinusoidal obstruction syndrome (SOS), a form of drug-induced liver injury related to oxaliplatin treatment, is associated with postoperative morbidity after hepatectomy. This study aimed to examine the impact of regorafenib, the first small-molecule kinase inhibitor to show efficacy against metastatic colorectal cancer, on a rat model of SOS. MethodsRats with monocrotaline (MCT)-induced SOS were divided into two groups according to treatment with either regorafenib (6 mg/kg) or vehicle alone, which were administered at 12 and 36 h, respectively, before MCT administration. Histopathologic examination and serum biochemistry tests were performed 48 h after MCT administration. Sinusoidal endothelial cells were evaluated by immunohistochemistry and electron microscopy. To examine whether regorafenib preserved remnant liver function, a 30% hepatectomy was performed in each group. ResultsThe rats in the vehicle group displayed typical SOS features, whereas these features were suppressed in the regorafenib group. The total SOS scores were significantly lower in the regorafenib group than in the vehicle group. Immunohistochemistry and electron microscopy showed that regorafenib had a protective effect on sinusoidal endothelial cells. The postoperative survival rate after 7 d was significantly better in the regorafenib group than that in the vehicle group (26.7% versus 6.7%, P < 0.05). Regorafenib reduced the phosphorylation of extracellular signal-regulated kinase, which induced matrix metalloproteinase-9 (MMP-9) activation and decreased the activity of MMP-9, one of the crucial mediators of SOS development. ConclusionsRegorafenib suppressed MCT-induced SOS, concomitant with attenuating extracellular signal-regulated kinase phosphorylation, and MMP-9 activation, suggesting that regorafenib may be a favorable agent for use in combination with oxaliplatin-based chemotherapy.

Stimulation of cannabinoid receptors by using Rubus coreanus extracts to control osteoporosis in aged male rats

A substantial proportion of men with prostatic disease have an increased risk of bone loss. In the present study, we investigated the effects of Rubus coreanus Miquel (RCM) extracts on osteoporosis that occurs with N-methyl-N-nitrosourea (MNU)-induced prostatic hyperplasia. The rats used in this study were categorized into groups of healthy controls, rats treated with MNU, and rats treated with MNU and RCM. The rats were sacrificed after 10 weeks of RCM treatment, after which ultrasonography, serum biochemical tests, histopathological examinations, immunohistochemical analysis, and semi-quantitative reverse-transcription polymerase chain reaction analysis were performed. There were no marked differences in body weight gain and the size and weight of the prostate gland between the MNU group and the MNU and RCM group. However, treatment with RCM inhibited osteoclastic osteolysis and reduced dysplastic progress in the prostate gland, as observed by histopathological evaluation and by analyzing changes in the levels of bone regulatory factors. In addition, the group treated with MNU and RCM had higher expression levels of cannabinoid receptors-1, -2, and osteoprotegerin. These results indicate that the anti-osteoporotic effect of RCM in prostatic hyperplasia is attributable to the cannabinoid receptor-related upregulation of osteoblastogenesis and inhibition of prostatic hyperplasia. The results of the present study suggest that treatment with RCM may benefit osteoporotic patients with prostatic disease by simultaneously altering the activation of osteoblasts and osteoclasts.