Search results for: PTP1B in-vitro anti-diabetic assay female albino mice

Authors: Endang Purwati Rahayuningsih

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The aim of this study is Enteropathogenic Eschericia coli O157 (EPEC) is one of the pathogen that can cause inflamation and damage intestinal mucosa, which is leading diarrhea. Inflamation in the intestinal mucosa proved by the presence of secretory Immunoglobulin A (sIgA) on the feces. Isolate dadih is Pediococcus pentosaceus (P. pentosaceus) as a probiotic lactic acid bacteria (LAB) is very usefull to improve sIgA and intestinal mucosa. The objective, to determine the dose and duration administration of P. pentosaceus for bowel frequence, sIgA level and height of illeum villi in mice EPEC-induced diarrhea. Method, using Complete Randomized design studies in mice EPEC-induced diarrhea. Mice was classified into 2 factors. A factor (dose of probiotic) and B factor (duration of probiotic observation) consisted of 0 hour, 12 hours, 24 hours and 36 hours. A factor consisted of negative control, positive control (mice induced by EPEC) and 3 different dose experimental mice. The results were a very significant interaction between dose and duration administration of P. pentosaceus. Mean of the most frequent defecation of mice EPEC-induced was 55 graetly reduced into 12 ,after 24 hours administration P. pentosaceus dose 2 x 1010 cfu/g, Mean of sIgA level of mice induced EPEC was 1,60 μg/ml, very significant different (p<0,01). Mean of sIgA level after 24 administration P. pentosaceus dose 2 x 1010cfu/g was 2,65 μg/ml. Mean of height of illeum villi after induced EPEC 53,04 μm with very significant different after 24 hours administration P. pentosaceus dose 2 x 1010cfu/g (142,881μm). This study concluded that P. pentosaceus dose 2 x 1010cfu/g after 24 hours is very beneficial to reduced bowel frequence, increase sIgA level and improve the height illeum villi of mice EPEC-induced diarrhea.

Keywords: Pediococcus pentosaceus, sIgA, enteropathogenic Eschericia coli O157, diarrhea, illeum villi

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Authors: Alireza Javed, Keivan Jamshidi

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Reactive amyloidosis is a condition that complicates a long list of chronic inflammation, chronic infectious, malignant, and hereditary disorders. In the present study the potential effects of two amyloidogenic substances: ie. AgNO3 and Freund's Adjuvant (AF) with that of vitamin free casein, on spatio-temporal pattern of experimental amyloidosis in mice, were compared. For this purpose, a total of 40 male Swees mice, obtained from Pasteur Institute Tehran, after being weighted were randomly divided into 4 groups including 2 treatments, 1 control (vitamin free casein) and 1 positive control (normal saline). At the end of 3rd, 5th and 7th weeks of experiment 3 mice were randomly selected and euthnised. Spleen sample of each animal obtained and preserved in 10% neutral buffer formalin. Sample were then processed through different stages of dehydration, clearing and impregnation and finally embedded in paraffin blocks. Sections of 5µm thickness then cut and stained by alkaline Congo red techniques. Spleen weights and the data obtained from the microscopic quantitative analysis did show no significant differences between groups A and B, A and C, and B and C. However, significant differences were observed between groups A and D, B and D, and C and D respectively. It is concluded that two compounds ie; AgNO3 and Freund's Adjuvant have the same potential, as does vitamin free casein have, in spatio – temporal pattern of experimental amyloidosis in mice.

Keywords: amyloidosis, mice, AgNO3, Freund's Adjuvant

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Authors: J. DeBoard, R. Dietrich, J. Hughes, K. Yurko, G. Harms

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Alzheimer’s disease (AD) is a predominant type of dementia and is likely a major cause of neural network impairment. The pathogenesis of this neurodegenerative disorder has yet to be fully elucidated. There are currently no known cures for the disease, and the best hope is to be able to detect it early enough to impede its progress. Beyond age and genetics, another prevalent risk factor for AD might be traumatic brain injury (TBI), which has similar neurodegenerative hallmarks. Our research focuses on obtaining information and methods to be able to predict when neurodegenerative effects might occur at a clinical level by observation of events at a cellular and molecular level in model mice. First, we wish to introduce our evidence that brain damage can be observed via brain imaging prior to the noticeable loss of neuromuscular control in model mice of AD. We then show our evidence that some blood biomarkers might be able to be early predictors of AD in the same model mice. Thus, we were interested to see if we might be able to predict which mice might show long-term neurodegenerative effects due to differing degrees of TBI and what level of TBI causes further damage and earlier death to the AD model mice. Upon application of TBIs via an apparatus to effectively induce extremely mild to mild TBIs, wild-type (WT) mice and AD mouse models were tested for cognition, neuromuscular control, olfactory ability, blood biomarkers, and brain imaging. Experiments are currently still in process, and more results are therefore forthcoming. Preliminary data suggest that neuromotor control diminishes as well as olfactory function for both AD and WT mice after the administration of five consecutive mild TBIs. Also, seizure activity increases significantly for both AD and WT after the administration of the five TBI treatment. If future data supports these findings, important implications about the effect of TBI on those at risk for AD might be possible.

Keywords: Alzheimer's disease, blood biomarker, neurodegeneration, neuromuscular control, olfaction, traumatic brain injury

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Authors: Alvin Han, Reema Shafi, Alishba Afaq, Jennifer Gommerman, Valeria Ramaglia, Shannon E. Dunn

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Adolescents engaged in contact-sports can suffer from recurrent brain concussions with no loss of consciousness and no need for hospitalization, yet they face the possibility of long-term neurocognitive problems. Recent studies suggest that head concussive injuries during adolescence can also predispose individuals to multiple sclerosis (MS). The underlying mechanisms of how brain concussions predispose to MS is not understood. Here, we hypothesize that: (1) recurrent brain concussions prime microglial cells, the tissue resident myeloid cells of the brain, setting them up for exacerbated responses when exposed to additional challenges later in life; and (2) brain concussions lead to the sensitization of myelin-specific T cells in the peripheral lymphoid organs. Towards addressing these hypotheses, we implemented a mouse model of closed head injury that uses a weight-drop device. First, we calibrated the model in male 12 week-old mice and established that a weight drop from a 3 cm height induced mild neurological symptoms (mean neurological score of 1.6+0.4 at 1 hour post-injury) from which the mice fully recovered by 72 hours post-trauma. Then, we performed immunohistochemistry on the brain of concussed mice at 72 hours post-trauma. Despite mice having recovered from all neurological symptoms, immunostaining for leukocytes (CD45) and IBA-1 revealed no peripheral immune infiltration, but an increase in the intensity of IBA1+ staining compared to uninjured controls, suggesting that resident microglia had acquired a more active phenotype. This microglia activation was most apparent in the white matter tracts in the brain and in the olfactory bulb. Immunostaining for the microglia-specific homeostatic marker TMEM119, showed a reduction in TMEM119+ area in the brain of concussed mice compared to uninjured controls, confirming a loss of this homeostatic signal by microglia after injury. Future studies will test whether single or repetitive concussive injury can worsen or accelerate autoimmunity in male and female mice. Understanding these mechanisms will guide the development of timed and targeted therapies to prevent MS from getting started in people at risk.

Keywords: concussion, microglia, microglial priming, multiple sclerosis

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Authors: Bouzidi Abdelouahab, Ghadjati Nadhra, Bettihi Sara, Mahdeb Nadia, Daamouche Z. El Youm

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The effects of acute administration of TOTAL alkaloids, the main active principle of Datura stramonium, with toxic properties, were studied in female Albino-Wistar rats. After acute intraperitoneal administration of dose 120 mg kg-1 (≈1/3 DL50) of total alkaloids to the seeds of D. stramonium, there were no remarkable changes in general appearance and no deaths occurred in any experimental group. After 5 days a significant reduction was observed in total alkaloids of seeds. The Red Blood Cells (RBC), Hematocrit (HCT) and Hemoglobin (HGB) show significant changes in the treated groups. There were no statistical differences in Glutamic-pyruvic Transaminase (GPT), Alkaline Phosphatase (ALP), urea, glucose and total protein observed between groups. After 24 h Glutamic-Oxaloacetic Transaminase (GOT) and creatinine were significantly higher in the treated male rats than the control group histological examination of liver showed no histopathological changes.

Keywords: datura stramonium, rat, liver, kidney, alkaloids, toxicity

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Authors: Kang-Hyun Leem, Myung-Gyou Kim, Hye Kyung Kim

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The prickly pear cactus (Opuntia ficus-indica) has a global distribution and have been used for medicinal benefits such as artherosclerosis, diabetes, gastritis, and hyperglycemia. However, very little information is currently available for their mechanism. The prikly pear variety Opuntia ficus-indica var. Saboten (OFS) is widely cultivated in Cheju Island, southwestern region of Korea, and used as a functional food. Present study investigated the effects of OFS on pancreatic β-cell function using pancreatic islet β cells (HIT cell). Alpha-glucosidase inhibition, glucose uptake, insulin secretion, insulin sensitivity, and pancreatic β cell proliferation were determined. The inhibitory effect of ethanol extract of OFS stem on α-glucosidase enzyme was measured in a cell free system. Glucose uptake was determined using fluorescent glucose analogue, 2-NBDG. Insulin secretion was measured by ELISA assay. Cell proliferation was measured by MTT assay. Ethanol extracts of OFS dose-dependently inhibited α-glucosidase activity as well as glucose uptake. Insulinotrophic effect of OFS extract was observed at high glucose media in pancreatic β-islet cells. Furthermore, pancreatic β cell regeneration was also observed.These results suggest that OFS mediates the antidiabetic activity mainly via α-glucosidase inhibition, glucose uptake, and improved insulin sensitivity.

Keywords: prickly pear cactus, Opuntia ficus-indica var. Saboten, pancreatic islet HIT cells, α-glucosidase, glucose uptake, insulinotrophic

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Authors: Abdul Soofi, Katherine Wolf, Egon Ranghini, Gregory Dressler

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Obesity and its associated complications, such as insulin resistance and non-alcoholic fatty liver disease, are reaching epidemic proportions. In mice, the TGF-β superfamily is implicated in the regulation of white and brown adipose tissues differentiation. The Kielin/Chordin-like Protein (KCP) is a secreted regulator of the TGF-β superfamily pathways that can inhibit both TGF-β and Activin signals while enhancing the Bone Morphogenetic protein (BMP) signaling. However, the effects of KCP on metabolism and obesity have not been studied in animal models. Thus, we examined the effects of KCP loss or gain of function in mice that were maintained on either a regular or a high fat diet. Loss of KCP sensitized mice to obesity and associated complications such as hepatic steatosis and glucose intolerance. In contrast, transgenic mice that expressed KCP in the kidney, liver and adipose tissues were resistant to developing high fat diet induced obesity and had significantly reduced white adipose tissue. KCP over-expression was able to shift the pattern of Smad signaling in vivo, to increase the levels of P-Smad1 and decrease P-Smad3, resulting in resistance to high fat diet induced hepatic steatosis and glucose intolerance. In aging mice, loss of KCP promoted liver pathology even when mice were fed a normal diet. The data demonstrate that shifting the TGF-β superfamily signaling with a secreted inhibitor or enhancer can alter the physiology of adipose tissue to reduce obesity and can inhibit the initiation and progression of hepatic steatosis to significantly reduce the effects of high fat diet induced metabolic disease.

Keywords: adipose tissue, KCP, obesity, TGF-β, BMP, hepatic steatosis, metabolic syndrome

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Authors: N. F. Hamid, A. Kipar, J. Stewart, D. J. Antoine, B. K. Park, D. P. Williams

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Acetaminophen (APAP) is a widely used analgesic that is safe at therapeutic doses. The mouse model of APAP has been extensively used for studies on pathogenesis and intervention of drug induced liver injury based on the CytP450 mediated formation of N-acetyl-p-benzo-quinoneimine and, more recently, as model for mechanism based biomarkers. Delay of the fasted CD1 mice to rebound to the basal level of hepatic GSH compare to fed mice is reported in this study. Histologically, 15 hours fasted mice prior to APAP treatment leading to overall more intense cell loss with no evidence of apoptosis as compared to non-fasted mice, where the apoptotic cells were clearly seen on cleaved caspase-3 immunostaining. After 15 hours post APAP administration, hepatocytes underwent stage of recovery with evidence of mitotic figures in fed mice and return to completely no histological difference to control at 24 hours. On the contrary, the evidence of ongoing cells damage and inflammatory cells infiltration are still present on fasted mice until the end of the study. To further measure the regenerative capacity of the hepatocytes, the inflammatory mediators of cytokines that involved in the progression or regression of the toxicity like TNF-α and IL-6 in liver and spleen using RT-qPCR were also included. Yet, quantification of proliferating cell nuclear antigen (PCNA) has demonstrated the time for hepatic regenerative in fasted is longer than that to fed mice. Together, these data would probably confirm that fasting prior to APAP treatment does not only modulate liver injury, but could have further effects to delay subsequent regeneration of the hepatocytes.

Keywords: acetaminophen, liver, proliferating cell nuclear antigen, regeneration, apoptosis

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Authors: Chao Wu

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Thioredoxin reductase 2 is a mitochondrial enzyme that belongs to the cellular defense against oxidative stress. We deleted mitochondrial Txnrd2 in a KrasG12D-driven pancreatic tumor model. Despite an initial increase in precursor lesions, tumor incidence decreased significantly. We isolated cancer cell lines from these genetically engineered mice and observed an impaired proliferation and colony formation. Reactive Oxygen Species, as determined by DCF fluorescence, were increased. We detected a higher mitochondrial copy number in Txnrd2-deficient cells (KTP). However, measurement of mitochondrial bioenergetics showed no impairment of mitochondrial function and comparable O₂-consumption and extracellular acidification rates. In addition, the mitochondrial complex composition was affected in Txnrd2 deleted cell lines. To gain better insight into the role of Txnrd2, we deleted Txnrd2 in clones from parental KrasG12D cell lines using Crispr/Cas9 technology. The deletion was confirmed by western blot and activity assay. Interestingly, and in line with previous RNA expression analysis, we saw changes in EMT markers in Txnrd2 deleted cell lines and control cell lines. This might help us explain the reduced tumor incidence in KrasG12D; Txnrd2∆panc mice.

Keywords: PDAC, TXNRD2, epithelial-to-mesenchymal-transition, ROS

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Authors: Martyna Chotomska, Aleksandra Studzinska, Marta Lisowska, Justyna Szubert, Aleksandra Tabis, Jacek Bania, Arkadiusz Miazek

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Objectives: Assessing antigen-specific T cell responses is of utmost importance for the pre-clinical testing of prototype vaccines against intracellular pathogens and tumor antigens. Mainly two types of in vitro assays are used for this purpose 1) enzyme-linked immunospot (ELISpot) and 2) intracellular cytokine staining (ICS). Both are time-consuming, relatively expensive, and require manual dexterity. Here, we assess if a straightforward detection of luciferase activity in blood samples of transgenic reporter mice expressing a secreted Lucia luciferase under the transcriptional control of IFN-γ promoter parallels the sensitivity of IFNγ ELISpot assay. Methods: IFN-γ-LUCIA mouse strain carrying multiple copies of Lucia luciferase transgene under the transcriptional control of IFNγ minimal promoter were generated by pronuclear injection of linear DNA. The specificity of transgene expression and mobilization was assessed in vitro using transgenic splenocytes exposed to various mitogens. The IFN-γ-LUCIA mice were immunized with 50mg of ovalbumin (OVA) emulsified in incomplete Freund’s adjuvant three times every two weeks by subcutaneous injections. Blood samples were collected before and five days after each immunization. Luciferase activity was assessed in blood serum. Peripheral blood mononuclear cells were separated and assessed for frequencies of OVA-specific IFNγ-secreting T cells. Results: We show that in vitro cultured splenocytes of IFN-γ-LUCIA mice respond by 2 and 3 fold increase in secreted luciferase activity to T cell mitogens concanavalin A and phorbol myristate acetate, respectively but fail to respond to B cell-stimulating E.coli lipopolysaccharide. Immunization of IFN-γ-LUCIA mice with OVA leads to over 4 fold increase in luciferase activity in blood serum five days post-immunization with a barely detectable increase in OVA-specific, IFNγ-secreting T cells by ELISpot. Second and third immunizations, further increase the luciferase activity and coincidently also increase the frequencies of OVA-specific T cells by ELISpot. Conclusions: We conclude that minimally invasive monitoring of luciferase secretions in blood serum of IFN-γ-LUCIA mice constitutes a sensitive method for evaluating primary and memory Th1 responses to protein antigens. As such, this method may complement existing methods for rapid immunogenicity assessment of prototype vaccines.

Keywords: ELISpot, immunogenicity, interferon-gamma, reporter mice, vaccines

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Authors: Moustafa Elhamouly, Masayuki Shimada

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The production of competent oocytes is essential for reproductivity in mammals. Maintenance of mitochondrial efficiency is required to supply the ATP necessary for granulosa cell proliferation during the follicular development process. Treatment with Pyrroloquinoline quinone (PQQ) has been reported to increase the number of ovulated oocytes and pups per delivery in mice by maintaining healthy mitochondrial function. This study aimed to elucidate how PQQ maintains mitochondrial function during ovarian follicle growth. To do this, both in vitro and in vivo experiments were performed with granulosa cells from superovulated immature (3-week-old) mice that were pretreated with or without PQQ. The effects of PQQ on beta-oxidation, mitochondrial function, mitophagy, and mitochondrial biogenesis were examined. PQQ increased beta-oxidation-related genes and CPT1 protein content in granulosa cells and this was associated with a decreased phosphorylation of P38 signaling protein. Using the fatty acid oxidation assay on the flux analyzer, PQQ increased the reliance of beta-oxidation on the endogenous fatty acids and was associated with a mild UCP-dependant mitochondrial uncoupling, ATP production, mitophagy, and mitochondrial biogenesis. PQQ also increased the expression of endogenous antioxidant enzymes. Thus, PQQ induced beta-oxidation in growing granulosa cells relying on endogenous fatty acids. And reduced the Reactive oxygen species (ROS) production by inducing a mild mitochondrial uncoupling with keeping high mitochondrial function. Damaged mitochondria were recycled by the induced mitophagy and replaced by the increased mitochondrial biogenesis. Collectively, PQQ may enhance reproductivity by maintaining the efficiency of mitochondria to produce enough ATP required for normal folliculogenesis.

Keywords: granulosa cells, mitochondrial uncoupling, mitophagy, pyrroloquinoline quinone (PQQ), reactive oxygen species (ROS).

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Authors: M. H. Rajikin, S. M. M. Syairah, A. R. Sharaniza

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Effects of nicotine on pre-partum body weight and preimplantation embryonic development has been reported previously. Present study was conducted to determine the effects of annatto (Bixa orellana)-derived delta-tocotrienol (TCT) (with presence of 10% gamma-TCT isomer) on the nicotine-induced reduction in body weight and 8-cell embryonic growth in mice. Twenty four 6-8 weeks old (23-25g) female balb/c mice were randomly divided into four groups (G1-G4; n=6). Those groups were subjected to the following treatments for 7 consecutive days: G1 (control) were gavaged with 0.1 ml tocopherol stripped corn oil, G2 was subcutaneously (s.c.) injected with 3 mg/kg/day of nicotine, G3 received concurrent treatment of nicotine (3 mg/kg/day) and 60 mg/kg/day of δ-TCT mixture (contains 90% delta & 10% gamma isomers) and G4 was given 60 mg/kg/day of δ-TCT mixture alone. Body weights were recorded daily during the treatment. On Day 8, females were superovulated with 5 IU Pregnant Mare’s Serum Gonadotropin (PMSG) for 48 hours followed with 5 IU human Chorionic Gonadotropin (hCG) before mated with males at the ratio of 1:1. Females were sacrificed by cervical dislocation for embryo collection 48 hours post-coitum. Collected embryos were cultured in vitro. Results showed that throughout Day 1 to Day 7, the body weight of nicotine treated group (G2) was significantly lower (p<0.05) than that of G1, G3 and G4. Intervention with δ-TCT mixture (G3) managed to increase the body weight close to the control group. This is also observed in the group treated with δ-TCT mixture alone (G4). The development of 8-cell embryos following in vitro culture (IVC) was totally inhibited in G2. Intervention with δ-TCT mixture (G3) resulted in the production of 8-cell embryos, although it was not up to that of the control group. Treatment with δ-TCT mixture alone (G4) caused significant increase in the average number of produced 8-cell embryo compared to G1. Present data indicated that δ-TCT mixture was able to reverse the body weight loss in nicotine treated mice and the development of 8-cell embryos was also improved.

Keywords: δ-tocotrienol, body weight, nicotine, preimplantation embryonic development

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Authors: Djebbar Atmani, Dina Kilani, Tristan Richard

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Medicinal plants are an important source for the discovery of potential new substances for use in medicine and food. Pistacia lentiscus, Fraxinus angustifolia and Clematis flammula, plants growing in the Mediterranean basin, are widely used in traditional medicine. Therefore, the present study was designed to investigate their antioxidant, anti-inflammatory, antidiabetic, anti-mutagenic/genotoxic and neuroprotective potential and identification of active compounds using appropriate methodology. Plant extracts and fractions exhibited high scavenging capacity against known radicals, enhanced superoxide dismutase and catalase activitiesand restored blood glucose levels, in vivo, to normal values, in agreement with the in vitro enzymatic inhibition data, through inhibition of amylase and glucosidase activities. Administration of Pistacia lentiscus extracts significantly decreased carrageenan-induced mice paw oedema and reduced effectively IL-1β levels in cell culture, whereas Fraxinus angustifolia extracts showed good healing capacity against wounds when applied topically on rabbits. Pistacia lentiscus and Fraxinus angustifolia extracts showed good neuro-protection and restored cognitive functions in mice, while Clematis flammula extracts showed potent anti-ulcerogenic activity associated to a promising anti-mutagenic/genotoxic activity. HPLC-MS and NMR analyses allowed the identification and structural elucidation of several known and new anthocyanins, flavonols and flavanols. Therefore, Pistacia lentiscus, Fraxinus angustifolia and Clematis flammulacould be used in palliative treatments against inflammatory conditions and diabetes complications, as well as against deterioration of cognitive functions.

Keywords: pistacia lentiscus, clematis flammula, fraxinus angustifolia, phenolic compounds, biological activity

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Authors: Hai Xu, Yiwei Wang, Xi Bao, Bihua Deng, Pengcheng Li, Yu Lu

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T7 phage could be used as a perfect vector for peptides expression and haptens presentation. T7-3GnRH recombinant phage was constructed by inserting three copies of Gonadotrophin Releasing Hormone (GnRH) gene into the multiple cloning site of T7 Select 415-1b phage genome. The positive T7-3GnRH phage was selected by using polymerase chain reaction amplification, and the p10B-3GnRH fusion protein was verified by SDS-PAGE and Western-blotting assay. T7-3GnRH vaccine was made and immunized with 10¹⁰ pfu in 0.2 ml per dose in mice. Blood samples were collected at an interval in weeks, and anti-GnRH antibody and testosterone concentrations were detected by ELISA and radioimmunoassay, respectively. The results show that T7-3GnRH phage particles confer a high immunogenicity to the GnRH-derived epitope. Moreover, the T7-3GnRH vaccine induced higher level of anti-GnRH antibody than ImproVac^®. However, the testosterone concentrations in both immunized groups were at a similar level, and the testis developments were significantly inhibited compared to controls. These findings demonstrated that the anti-GnRH antibody could neutralize the endogenous GnRH to down regulate testosterone level and limit testis development, highlighting the potential value of T7-3GnRH in the immunocastration vaccine research.

Keywords: Gonadotrophin Releasing Hormone (GnRH), Immunocastration, T7 phage, Phage vaccine

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Authors: Fatimah A. Alhomaid, Nadia H. Mahmoud, Maha A. Al-Qaraawi

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The present study was designed to induce hyperhomocysteinemia (HHcy) in elderly male and female rats. Also,to evaluate, the effect of (HHcy) as a risk factor for cerebrovascular disease and brain atrophy and folate supplementation on serum levels of Hcy, total cholesterol, low density lipoprotein cholesterol (LDLc), high density lipoprotein cholesterol (HDLc), triglycerides, pyridoxal phosphate , folate also, histopathological examination of brain and cerebrovascular vessels In this work 50 male and 50 female elderly albino rats were used and divided into five groups. The first group served as control, the second and third group received two different dose of L-methionine, the fourth and fifth group received fortified diet with folate powder plus L-methionine. Our results showed that homocysteine levels in male and female rats that received low and high dose of methionine were higher than in the control group, while the levels of folate significantly decreased in male rats only. Induced hyperhomocysteinemia in elderly male and female rats led to significant increase in serum level of cholesterol, LDLc and triglycerides but serum level of HDLc were significantly lower in methionine treated male and female rats than in control. Our results showed that a strong positive correlation between all these parameters and homocysteine except HDLc levels which correlate negatively to Hcy levels. Administration of folate to methionine treated male rats led to insignificant changes in the level of cholesterol when compared to control group but this level was found to be significantly decrease in female rats received small dose of methionine. When the level of cholesterol compared to the same dose of methionine treated group we found a significant decrease in both male and female rats. LDLc and triglycerides level significantly decrease in male rats only versus the control rats, while when compared to low and high dose of methionine a significant decreased occurs. A significant increase in serum level of HDLc in male and female rats when compared to both control and methionine treated groups. In male and female rats supplemented with folate we found an increased serum levels of folate when compared to rats received both dose of methionine. The levels of pyridoxal phosphate significantly decreased in all treated rats compared to the control group and its level were increased with supplementation of folate versus the rats received small and large dose of methionine. It can be concluded that hyperhomocysteinemia may be an additional risk factor for cerebrovascular atherosclesosis and brain atrophy in elderly people and diatery supplementation with folate blocking the activity of homocysteine and may be considered as a therapeutic possibility.

Keywords: hyperhomocysteinemia, brain atrophy, cerebrovascular, L-methionine, pyridoxal phosphate

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Authors: Shaban Saad, Syed Ahmed, Suher Aburawi, Isabel Fong

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Ruta graveolens is a plant commonly found in north Africa and south Europe. It is reported that Ruta graveolens is used traditionally for epilepsy and some other illnesses. The acute and sub-acute effects of alcoholic extract residue were tested for possible anti-epileptic and skeletal muscle relaxation activity. The effect of extract on rat spontaneous motor activity (SMA) was also investigated using open filed. We previously proved the anti convulsant activity of the plant against pentylenetetrazol and electrically induced convulsions. Therefore in this study strychnine was used to induce convulsions in order to explore the mechanism of anti-convulsant activity of the plant. The skeletal muscle relaxation activity of Ruta graveolens was studied using pull-up and rod hanging tests in rats. At concentration of 5%w/v the extract protected mice against strychnine induced myoclonic jerks and death. The pull-up and rod hanging tests pointed to a skeletal muscle relaxant activity at higher concentrations. Ruta graveolens extract also significantly decreased the number of squares visited by rats in open field apparatus at all tested concentrations (3.5-20%w/v). However, the significant decrease in number of rearings was only noticed at concentrations of (15 and 20%w/v). The results indicate that Ruta graveolens contains compound(s) capable to inhibit convulsions, decrease SMA and/or diminish skeletal muscle tone in animal models. This data and the previously generated data together point to a general depression trend of CNS produced by Ruta graveolens.

Keywords: Ruta graveolens, open field, skeletal muscle relaxation

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Authors: Xing Lv, Hui-Qin Xu

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The present study aimed to reveal the mechanism in aggravating STZ induced diabetic nephropathy (DN) by AGEs (advanced glycation end products). At the eighth day, 20 diabetic mice were randomly divided into STZ group and combination (combine AGEs with STZ) group. Simultaneously, AGEs group and normal group were set. Only mice in AGEs group, combination group were fed with high-AGEs diets. Mice diabetic conventional indicators, biochemical analysis were measured. Among the indictors, food consumptions, water intake, urine output, blood glucose, urine protein, urine creatinine, serum urea nitrogen were increased significantly in STZ, combination groups. The AGEs levels in combination group increased significantly when compared with STZ group. Weights and insulin levels in the STZ, combination groups were decreased significantly when compared with normal group, and the difference was significantly between AGEs group and STZ group. As a conclusion, AGEs play an important role in the DN development, inducing kidney damages.

Keywords: AGEs, diabetic nephropathy, serum urea nitrogen, urine protein

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Authors: Saqib Ali, Man-Qun Wang

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The Japanese pine sawyer, Monochamus alternatus Hope (Coleoptera: Cerambycidae), is a major pest of pines and it is also the key vector of the exotic pinewood nematode in China. In the present study, we cloned, expressed, and purified a chemosensory protein (CSP) in M. alternatus. We surveyed its expression in various developmental stages of male and female adult tissues and determined its binding affinities for different pine volatiles using a competitive binding fluorescence assay. A CSP known as CSP5 in M. alternatus was obtained from an antennal cDNA library and expressed in Escherichia coli. Quantitative reverse transcription polymerase chain reaction results indicated that the CSP5 gene was mainly expressed in male and female antennae. Competitive binding assays were performed to test the binding affinity of recombinant CSP5 to 13 odour molecules of pine volatiles. The results showed that CSP5 showed very strong binding abilities to myrcene, (+)-β-pinene, and (−)-isolongifolene, whereas the volatiles 2-methoxy-4-vinylphenol, p-cymene, and (+)-limonene oxide have relatively weak binding affinity at pH 5.0. Three volatiles myrcene, (+)-β-pinene, and (−)-isolongifolene may play crucial roles in CSP5 binding with ligands, but this needs further study for confirmation. The sensitivity of insect to host plant volatiles can effectively be used to control and monitor the population through mass trapping as part of integrated pest management programs.

Keywords: olfactory-specific protein, volatiles, competitive binding assay, expression characteristics, qPCR

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Authors: Min-Ju Jo, Min-Young Um, Moonsung Choi, Sooim Shin

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Type 2 diabetes (T2D) is characterized by insulin resistance, the inability of β-cell and the dysfunction of mitochondria. To characterize effects of Cassia tora extract on mitochondrial dysfunction related T2D, the reduced glutathione level, amount of mitochondrial complexes and activities of mitochondrial complexes were measured. Three groups of mice were modeled; a control group was fed a normal diet, a diabetic group was fed a diabetic diet high in fat and carbohydrates, and a third group was fed a diabetic diet + 70% ethanol extracted Cassia tora seeds for 12 weeks. The amount of mitochondria was determined by Bradford assay after isolation of mitochondria in liver from each group. During isolation of mitochondria, cytosolic fractions of the tissue were collected to measure the reduced glutathione level. Interestingly, high level of the reduced glutathione was observed in Cassia tora treated group and decreased activities of mitochondrial complexes in Cassia tora treated group compared to the diabetic diet group. It indicates that Cassia tora has the potential to increase the reduced form of glutathione functioned as an important antioxidant in cells, and to reduce mitochondrial metabolic compensatory mechanism.

Keywords: antioxidant, Cassia tora, diabetes, electron transport chain, glutathione, mitochondria, spectrophotometry

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Authors: V. Nigam, V. Nambiar

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Aegle Marmelos leaf has been used as a remedy for various gastrointestinal infections and lowering blood sugar level in traditional system of medicine in India due to the presence of various constituents such as flavonoids, tannins and alkaloids (eg. Aegelin, Marmelosin, Luvangetin).The objective of the present study was to evaluate the total antioxidant activity, total and individual phenol content of the wild and cultivated variety of Aegle marmelos leaves to assess the role of this plant in ethanomedicine in India. The methanolic extracts of the leaves were screened for total antioxidant capacity through Ferric Reducing Antioxidant Potential (FRAP) and 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay; Total Phenol content (TPC) through spectrophotometric technique based on Folin Ciocalteau assay and for qualitative estimation of phenols, High performance Liquid Chromatography was used. The TPC of wild and cultivated variety was 7.6% and 6.5% respectively whereas HPLC analysis for quantification of individual polyphenol revealed the presence of gallic acid, chlorogenic acid and Ferullic acid in wild variety whereas gallic acid, Ferullic acid and pyrocatechol in cultivated variety. FRAP values and IC 50 value (DPPH) for wild and cultivated variety was 14.65 μmol/l and 11.80μmol/l; 437 μg/ml and 620μg/ml respectively and thus it can be used as potential inhibitor of free radicals. The wild variety was having more antioxidant capacity than the cultivated one it can be exploited further for its therapeutic application. As Aegle marmelos is rich in antioxidant, it can be used as food additives to delay the oxidative deterioration of foods and as nutraceutical in medicinal formulation against degenerative diseases like diabetes.

Keywords: antioxidant activity, aegle marmelos, antidiabetic, nutraceutical

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Authors: Khalil Abdullah Ahmed Khalil, Elsadig Mohamed Ahmed

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Extracts of various plants material capable of decreasing blood sugar have been tested in experimental animal models and their effects confirmed. Neem or Margose (Azadirachta Indica) is an indigenous plant believed to have antiviral, antifungal, antidiabetic and many other properties. This paper deals with a comparative study of the effect of aqueous Neem leaves extract alone or in combination with glibenclamide on alloxan diabetic rabbits. Administration of crude aqueous Neem extract (CANE) alone (1.5 ml/kg/day), as well as the combination of CANE (1.5 ml/kg/day) with glibenclamide (0.25 mg/kg/day) significantly, decreased (P<0.05) the concentrations of serum lipids, blood glucose and lipoprotein VLDL(very low-density lipoproteins) and LDL(low-density lipoproteins) but significantly increased (P<0.05) the concentration of HDL(high-density lipoprotein). The change was observed significantly greater when the treatment was given in combination of CANE and glibenclamid than with CANE alone.

Keywords: neem, hypoglycemic, hypolipidemic, cholesterol

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Authors: Mrinal Gupta, Mohammad Rumman, Babita Singh Abbas Ali Mahdi, Shivani Pandey

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Introduction: Berberine (BBR), a bioactive compound isolated from Coptidis Rhizoma, possesses diverse pharmacological activities, including anti-bacterial, anti-inflammatory, antitumor, hypolipidemic, and anti-diabetic. However, its role as an anti-diabetic agent in animal models of dexamethasone (Dex)-induced diabetes remains unknown. Studies have shown that natural compounds, including aloe, caper, cinnamon, cocoa, green and black tea, and turmeric, can be used for treating Type 2 diabetes mellitus (DM). Compared to conventional drugs, natural compounds have fewer side effects and are easily available. Herein, we studied the anti-diabetic effects of BBR in a mice model of Dex-induced diabetes. Methods: HepG2 cell line was used for glucose release and glycogen synthesis studies. Cell proliferation was measured by methylthiotetrazole (MTT) assay. For animal studies, mice were treated with Dex (2 mg/kg, i.m.) for 30 days and the effect of BBR at the doses 100, 200, and 500 mg/kg (p.o.) was analyzed. Glucose, insulin, and pyruvate tests were performed to evaluate the development of the diabetic model. An echo MRI was performed to assess the fat mass. Further, to elucidate the mechanism of action of BBR, mRNA expression of genes regulating gluconeogenesis, glucose uptake, and glycolysis were analyzed. Results: In vitro BBR had no impact on cell viability up to a concentration of 50μM. Moreover, BBR suppressed the hepatic glucose release and improved glucose tolerance in HepG2 cells. In vivo, BBR improved glucose homeostasis in diabetic mice, as evidenced by enhanced glucose clearance, increased glycolysis, elevated glucose uptake, and decreased gluconeogenesis. Further, Dex treatment increased the total fat mass in mice, which was ameliorated by BBR treatment. Conclusion: BBR improves glucose tolerance by increasing glucose clearance, inhibiting hepatic glucose release, and decreasing obesity. Thus, BBR may become a potential therapeutic agent for treating glucocorticoid-induced diabetes and obesity in the future.

Keywords: glucocorticoid, hyperglycemia, berberine, HepG2 cells, insulin resistance, glucose

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Authors: Joseph Bamidele Minari

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The anti-jaundice properties of the methanolic extract of Carica papaya leaves on albino rat was evaluated. In order to achieve this, the phytochemical screening of the extract was carried out, and carbon tetrachloride (CCl4) (i.p) was injected into albino rats to induce jaundice. The rats were simultaneously given oral doses of 20 mg/kg, 40 mg/kg, 60 mg/kg, 80 mg/kg and 100 mg/kg (p.o) of methanolic extract of C. papaya. The effects of these extract on total bilirubin concentration, liver ALT AST, GGT activities of the jaundice-induced rats were studied after seven days period of the experiment. Administration of CCl4 alone to the rats significantly increased (p<0.05) total bilirubin concentration while the activities of ALT, AST, and GGT in the liver when compared to controls which received distilled water (p.o) was significantly lower (p<0.05). Simultaneous treatment of CCl4 injection, and oral administration of different doses of the C. papaya extract significantly reduced (p<0.05) total bilirubin concentration in the serum while the liver ALT AST, GGT activities significantly increased (p < 0.05). However, the lowest significant reduction (p<0.05) of bilirubin concentration was observed with simultaneous administration of 60mg/kg of the extract on the rats. This study suggests that the extract of C. papaya leaves possess the phytochemicals that have anti-jaundice properties.

Keywords: carica papaya, jaundice, herbal medicine, liver, rat

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Authors: Pureun-Haneul Lee, Byeong-Gon Kim, Sun-Hye Lee, An-Soo Jang

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Background: Nanoparticles may pose adverse health effects due to particulate matter inhalation. Nanoparticle exposure induces cell and tissue damage, causing local and systemic inflammatory responses. The inflammasome is a major regulator of inflammation through its activation of pro-caspase-1, which cleaves pro-interleukin-1β (IL-1β) into its mature form and may signal acute and chronic immune responses to nanoparticles. Objective: The aim of the study was to identify whether nanoparticles exaggerates inflammasome pathway leading to airway inflammation and hyperresponsiveness in an allergic mice model of asthma. Methods: Mice were treated with saline (sham), OVA-sensitized and challenged (OVA), or titanium dioxide nanoparticles. Lung interleukin 1 beta (IL-1β), interleukin 18 (IL-18), NACHT, LRR and PYD domains-containing protein 3 (NLRP3) and caspase-1 levels were assessed with Western Blot. Caspase-1 was checked by immunohistochemical staining. Reactive oxygen species were measured for the marker 8-isoprostane and carbonyl by ELISA. Results: Airway inflammation and hyperresponsiveness increased in OVA-sensitized/challenged mice and these responses were exaggerated by TiO2 nanoparticles exposure. TiO2 nanoparticles treatment increased IL-1β and IL-18 protein expression in OVA-sensitized/challenged mice. TiO2 nanoparticles augmented the expression of NLRP3 and caspase-1 leading to the formation of an active caspase-1 in the lung. Lung caspase-1 expression was increased in OVA-sensitized/challenged mice and these responses were exaggerated by TiO2 nanoparticles exposure. Reactive oxygen species was increased in OVA-sensitized/challenged mice and in OVA-sensitized/challenged plus TiO2 exposed mice. Conclusion: Our data demonstrate that inflammasome pathway activates in asthmatic lungs following nanoparticles exposure, suggesting that targeting the inflammasome may help control nanoparticles-induced airway inflammation and responsiveness.

Keywords: bronchial asthma, inflammation, inflammasome, nanoparticles

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Authors: P. Singh, R. M. Banik

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Artificial neural network (ANN) was employed to optimize assay parameters viz., time, temperature, pH of reaction mixture, enzyme volume and substrate concentration of L-glutaminase from Bacillus cereus MTCC 1305. ANN model showed high value of coefficient of determination (0.9999), low value of root mean square error (0.6697) and low value of absolute average deviation. A multilayer perceptron neural network trained with an error back-propagation algorithm was incorporated for developing a predictive model and its topology was obtained as 5-3-1 after applying Levenberg Marquardt (LM) training algorithm. The predicted activity of L-glutaminase was obtained as 633.7349 U/l by considering optimum assay parameters, viz., pH of reaction mixture (7.5), reaction time (20 minutes), incubation temperature (35˚C), substrate concentration (40mM), and enzyme volume (0.5ml). The predicted data was verified by running experiment at simulated optimum assay condition and activity was obtained as 634.00 U/l. The application of ANN model for optimization of assay conditions improved the activity of L-glutaminase by 1.499 fold.

Keywords: Bacillus cereus, L-glutaminase, assay parameters, artificial neural network

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Authors: Rania Hanafi Said, Rasha Mohamed Taha

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Background: By using nanoparticles as drug delivery, it may be possible to avoid the drawbacks of systemic antibiotic dosing, including bacterial antibiotic resistance. The goal of this study was to see how well tetracycline loaded on nanochitosan worked to treat gingival inflammation in albino rats caused by Porphyromonas gingivalis. The study analyzed immunohistochemically the localization of the pro-inflammatory cytokine Interleukin-1beta (IL-1β). Material and methods: In this study, fifty mature male albino rats weighing 150 to 180 grams each were used. They were randomly divided into five groups. We checked for weight changes in rats. Ten male albino rats were included in Group I, which served as a negative control group. Ten rats were included in Group II, where they were exposed once to Porphyromonas. Group III contained ten rats, which were treated the same as Group II plus daily injections of diluted tetracycline powder at the infection sites. Ten rats in Group IV received the same procedure as those in Group II before receiving daily injections of nanochitosan at the injection sites. Finally, Group V, which had ten rats. Following the same protocol as Group II, they received localized injections of tetracycline loaded on nanochitosan once daily. Rats' gingivae were extracted and prepared after they were anesthetized. The biopsies were examined histologically and immunohistochemically by light microscopy. Results: Groups I and V had a nearly normal histological appearance of gingival tissue. In Groups II, III, and IV, degeneration was seen because the epithelial cells were bigger, collagen fibers were pulling away from the lamina propria connective tissue, and the basement membranes had come to an end. There was no discernible difference between groups V and I when they were examined immunohistochemically. Conclusion: The use of nano chitosan as a tetracycline carrier is a novel technique to overcome the drug's rising level of resistance.

Keywords: Immunohistochemistry, Nanochitosan, porphyromonas gingivitis, Tetracycline

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Authors: Dilek Ozturk, Narin Ozturk, Zeliha Pala Kara, Engin Kaptan, Serap Sancar Bas, Nurten Ozsoy, Alper Okyar

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Most physiological processes oscillate in a rhythmic manner in mammals including metabolism and energy homeostasis, locomotor activity, hormone secretion, immune and endocrine system functions. Endocrine body rhythms are tightly regulated by the circadian timing system. The hypothalamic-pituitary-thyroid (HPT) axis is under circadian control at multiple levels from hypothalamus to thyroid gland. Since circadian timing system controls a variety of biological functions in mammals, circadian rhythms of biological functions may modify the drug tolerability/toxicity depending on the dosing time. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer agent that is active against many cancers. It was also found to be active in medullary thyroid cancer. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus on the thyroid gland and hormones in mice. Healthy C57BL/6J mice were synchronized with 12h:12h Light-Dark cycle (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding to Light onset). Everolimus was administered to male (5 mg/kg/day) and female mice (15 mg/kg/day) orally at ZT1-rest period- and ZT13-activity period- for 4 weeks; body weight loss, clinical signs and possible changes in serum thyroid hormone levels (TSH and free T4) were examined. Histological alterations in the thyroid gland were evaluated according to the following criteria: follicular size, colloid density and viscidity, height of the follicular epithelium and the presence of necrotic cells. The statistical significance between differences was analyzed with ANOVA. Study findings included everolimus-related diarrhea, decreased activity, decreased body weight gains, alterations in serum TSH levels, and histopathological changes in thyroid gland. Decreases in mean body weight gains were more evident in mice treated at ZT1 as compared to ZT13 (p < 0.001, for both sexes). Control tissue sections of thyroid glands exhibited well-organized histoarchitecture when compared to everolimus-treated groups. Everolimus caused histopathological alterations in thyroid glands in male (5 mg/kg, slightly) and female mice (15 mg/kg; p < 0.01 for both ZT as compared to their controls) irrespective of dosing-time. TSH levels were slightly decreased upon everolimus treatment at ZT13 in both males and females. Conversely, increases in TSH levels were observed when everolimus treated at ZT1 in both males (5 mg/kg; p < 0.05) and females (15 mg/kg; slightly). No statistically significant alterations in serum free T4 levels were observed. TSH and free T4 is clinically important thyroid hormones since a number of disease states have been linked to alterations in these hormones. Serum free T4 levels within the normal ranges in the presence of abnormal serum TSH levels in everolimus treated mice may suggest subclinical thyroid disease which may have repercussions on the cardiovascular system, as well as on other organs and systems. Our study has revealed the histological damage on thyroid gland induced by subacute everolimus administration, this effect was irrespective of dosing time. However, based on the body weight changes and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13 in both male and females. Yet, effects of everolimus on thyroid functions may deserve further studies regarding their clinical importance and chronotoxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, thyroid gland, thyroid hormones

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Authors: Austin Belfiori, Kevin Rinek, Zach Barcroft, Jennifer Berglind

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Diet influences the composition of the gut microbiota and host's health. Disruption of the balance among the microbiota, epithelial cells, and resident immune cells in the intestine is involved in the pathogenesis of inflammatory bowel disease (IBD). To study the role of gut microbiota in intestinal inflammation, the microbiome of control mice (C57BL6) given a gluten-containing standard diet versus C57BL6 mice given the gluten-free (GF) feed (n=10 in each group) was examined. All mice received the 3% DSS for 5 days. Throughout the study, feces were collected and processed for DNA extraction and MiSeq Illumina sequencing of V4 region of bacterial 16S rRNA gene. Alpha and beta diversities and compositional differences at phylum and genus levels were determined in intestinal microbiota. The mice receiving the GF diet showed a significantly increased abundance of Firmicutes and a decrease of Bacteroides and Lactobacillus at phylum level. Therefore, the gluten free diet led to reductions in beneficial gut bacteria populations. These findings indicate a role of wheat gluten in dysbiosis of the intestinal microbiota.

Keywords: gluten, colitis, microbiota, DSS, dextran sulphate sodium

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Authors: Sang-Sun Yoon, Yea-Hyun Leem, Sangmee Ahn Jo

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The N-acetylated-alpha-linked-acidic (NAAG) peptidase inhibitor 2-phosphonomethyl pentanedioic acid (2-PMPA) has demonstrated to be neuroprotective against glutamate-mediated neuron degeneration and neurological disorders such as ischemia. Several studies have demonstrated impaired psychiatric function by altered glutamate carboxypeptidase II expression, although 2-PMPA has not yet been studied. Thus, we investigated effect of 2-PMPA on depressive-like phenotype using C57BL/6 mice. Treatment of 2-PMPA (10 mg/kg for 6 days/daily, ip injection) on C57BL/6 naïve mice showed depressive-like symptoms such as decreased social preference, but did not affect the immobility measured by tail suspension test. Reduction of phosphorylated cAMP-responsive element binding (p-CREB) known as a representative marker of depressive-like behavior was observed in layer 1 and piriform cortex subregions of the prefrontal cortex of 2-PMPA-treated mice. The immunoreactivity of metabotropic glutamate receptors 5 (mGluR5) that mediate phosphorylation of CREB was also decreased in layer 1 and piriform cortex subregions of the prefrontal cortex of 2-PMPA injected mice. Thus, our results suggest that dysregulation of the GCPII or NAAG by 2-PMPA treatment is likely to be associated with pathogenesis of depression and further studies are needed to understand whether the reduced NAAG level or enhanced glutamate level in the brain is involved in this response.

Keywords: depression, GCPII, 2-PMPA, p-CREB, mGluR5

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Authors: Kathy Stein, Mariola Lysson, Anja Schmidt, Beatrix Schumak, Sabine Specht, Hicham Bouabe, Jürgen Heesemann, Axel Roers, Joerg C. Kalff, Sven Wehner

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Objective: Postoperative ileus (POI) is a common complication of abdominal surgery. Monocyte infiltration is a hallmark of POI. The polarization of macrophages/monocytes in this process is not well understood. We aimed to investigate if and how M2 macrophage/monocyte differentiation is involved in POI pathogenesis. Design: POI was induced by intestinal manipulation (IM). C57Bl/6, CCR2-/-, IL-10 reporter (ITIB), IL-10-/- and LysMcre/IL-10fl/fl mice underwent IM. At various points in time leukocyte influx, gene and protein expression of cytokines, chemokines and M2 differentiation markers and intestinal motility were analyzed. Results: IM induced the postoperative expression of the M2 markers Arginase-1 and YM-1, predominantly in F4/80+Ly6C+ monocytes. Gene expression analyses indicated an IL-10-dependent, IL-4-independent M2 polarization of these monocytes. IL-10 dependency of M2 differentiation was confirmed in IL-10 deficient mice. Leukocytes, in the order of infiltrating monocytes, neutrophils, and resident macrophages were the main IL-10 producers during POI. IL-10 producing monocytes as well as M2 marker expression were almost absent in CCR2-deficient mice. However, postoperative IL-10 expression was not altered in CCR2-/- mice. The loss of M2 polarized monocytes neither protected CCR2-/- mice from nor affected resolution of POI. In contrast, IL-10 deficiency reduced postoperative neutrophil numbers and ameliorated POI. IL-10Ra expression was strongly induced in neutrophils but not in monocytes. Conclusion: We conclude that IL-10 counteracts POI resolution by activating IL-10Ra-expressing neutrophils in the late phase of disease while IL-10-dependent M2 differentiation is not pivotal to POI manifestation and resolution.

Keywords: interleukin-10, macrophages, neutrophils, postoperative ileus

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